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Method and system for recording video data |
The invention relates to a recording method whereby a communication link, preferably specifically in one venue, is established in at least one venue between a telephone, particularly the mobile telephone of a user, and a camera system installed in said venue. The video data is recorded by the camera system, whereby the user can have an interactive function. The invention also relates to a system for recording video data. |
1. Recording method in which a communication link, in particular a communication link specific to a venue or scene, is set up at at least one venue or scene between a telephone, in particular a mobile telephone of a user and a camera system installed at the scene and video data are recorded by means of the camera system with a user as a participant. 2. Method in accordance with claim 1, wherein the camera system is called via a telephone number specific to the scene by means of the telephone for the setting up of the communication link. 3. Method in accordance with claim 1 wherein at least one, preferably precisely one, telephone number specific to the scene is displayed on a display device, in particular a placard, a poster or a monitor, installed at the scene with the display device in particular being used as a background during the recording. 4. Method in accordance with claim 1, wherein a running recording at the scene is displayed visually and/or acoustically, in particular on a display device. 5. Method in accordance with claim 1, wherein audio data is picked up, and in particular stored, via the telephone and/or in that audio data is picked up, and in particular stored, via a sound recording system installed at the scene. 6. Method in accordance with claim 1, wherein the camera system operates automatically and in particular in accordance with an at least substantially pre-settable recording procedure which can preferably be influenced via the telephone and/or wherein the camera system is activated, deactivated and/or controlled via a recording unit and/or via the telephone. 7. Method in accordance with claim 1, wherein the communication link is set up between the telephone and a recording unit serving for the communication with the camera system and in particular for the control of the camera system. 8. Method in accordance with claim 1, wherein technical recording equipment, in particular for the lighting and/or sound recording, installed at the scene is activated, deactivated and/or controlled subsequent to the setting up of the communication link, in particular via a recording unit and/or via the telephone. 9. Method in accordance with claim 1, wherein a communications unit, in particular in the form of a speech computer, is used for the communication with the user and/or in that voice messages, in particular information, instructions, explanations and/or direction instructions, are preferably communicated to the user via the telephone by menu control. 10. Method in accordance with claim 1, wherein user data, in particular relating to the specific user and/or to the respective recording, are communicated to a recording unit, and in particular stored, via the telephone, in particular via a keypad of the telephone and/or in that a distinction is made by means of stored user data and/or pre-settable criteria between at least temporarily blocked users, on the one hand, and users who are to be accepted and who preferably satisfy pre-settable selection criteria, on the other hand. 11. Method in accordance with claim 1, wherein at least the recorded data including the video data is preferably stored at the scene and/or wherein the recorded data at least including the video data, and in particular recording data stored at the scene, is transmitted via a communication network or a data network, in particular via an existing telephone network, to a place which is preferably spatially separated from the scene, in particular to an Internet server or to a central recording facility and/or wherein the recorded data at least including the video data is broadcast on television and/or made available on the Internet. 12. Method in accordance with claim 1, wherein a live recording of the scene is made available, in particular on the Internet, at times or at least substantially without interruption, by means of the camera system, with definable recording sections with respect to the time of starting and of ending being stored by means of the telephone. 13. Method in accordance with claim 1, wherein the video data is subjected to later processing and is in particular combined with recorded audio data, preferably synchronised. 14. Method in accordance with claim 1, wherein video data are recorded at a plurality of spatially separated scenes and/or wherein the setting up of a communication link is prevented outside of a restricted region containing the respective scene, but no further scene. 15. Method in accordance with claim 1, wherein a publicly accessible place is selected as a scene, in particular a square or a street; and/or in that a building is selected as the scene, in particular a restaurant, a discotheque, a cinema or an event hall, preferably a building part designed as a stage. 16. System for the recording of video data at at least one scene, in particular for carrying out the method of claim 1, having at least one camera system installed at the scene to which a communication link preferably a scene-specific communication link can be set up with a telephone located at the scene, in particular a mobile telephone of a user and can be operated with an established communication link for the recording of video data with the user as participant. 17. System in accordance with claim 16, wherein the camera system can be called up by means of the telephone via at least one telephone number specific to the scene. 18. System in accordance with claim 16, wherein at least one display device is provided which is installed at the scene on which at least one and preferably precisely one telephone number specific to the scene is displayed or can be displayed, with a placard, a poster or a monitor in particular being provided as the display device and/or in that the display device is formed as a recording background. 19. System in accordance with claim 16, wherein a display unit installed at the scene is provided with which a running recording can be indicated optically and/or acoustically, in particular in the form of a coloured light signal and/or an illuminated written display, with the display unit preferably being integrated into a device for displaying at least one telephone number specific to the scene. 20. System in accordance with claim 16, wherein audio data transmitted via the telephone of the user can be recorded, and in particular stored, and/or in that a sound recording system installed at the scene is provided for the recording of in particular storable audio data. 21. System in accordance with claim 16, wherein the camera system is automatically operatable and in particular in accordance with an at least substantially pre-determinable recording procedure, which can preferably be influenced via the telephone. 22. System in accordance with claim 16, wherein a recording unit is provided which is designed for communication with the telephone and with the camera system, and in particular for the control of the camera system, with the recording unit in particular being installed at the scene and in particular being arranged in the spatial vicinity of the camera system and preferably being integrated into the camera system. 23. System in accordance with claim 22, wherein the recording unit includes a communication unit, in particular in the form of a speech computer, for the communication with the user, with speech messages, in particular information, instructions, explanations, and/or direction explanations being conveyable to the user, preferably under menu control, in particular by means of the communication unit via the telephone. 24. System in accordance with claim 22, wherein the recording unit comprises a control unit, in particular a computer-controlled control unit, for the communication with the camera system. 25. System in accordance with claim 16, wherein user data, in particular user specific data and/or data relating to the respective recording, can be conveyed to a recording unit and are is in particular storable via the telephone, in particular via a keyboard of the telephone and/or wherein an evaluation unit is provided which is designed to distinguish between at least temporarily blocked users on the one hand and users which are to be allowed and which preferably satisfy pre-determinable selection criteria on the other hand, by comparison of transmitted user data of calling users with stored user data and/or pre-determinable criteria, with the evaluation unit preferably being integrated into the recording unit. 26. System in accordance with claim 16, wherein a storage device is provided for the storage of recording data including at least the video data, in particular in a databank, with the storage device preferably being installed at the scene and in particular being integrated into the camera system or into a recording unit. 27. System in accordance with claim 16, wherein the recording data including at least the video data and in particular the recording data stored at the scene can be transmitted via a communication network or data network, in particular via an existing telephone network, to a location spatially separate from the scene, with the recording data in particular being transmittable to an internet server spatially separate from the scene and/or wherein the recording data can be transmitted to a recording center spatially separated from the scene. 28. System in accordance with claim 16, wherein video data stored in particular in a recording unit and/or on an internet server can be called up in reduced image quality for preview and/or selection purposes. 29. System in accordance with claim 16, wherein a plurality of camera systems are provided which are associated with various scenes and/or in that a common recording center is associated with a plurality of spatially separated scenes. |
Environmental Performance Assessment |
Abstract of the Disclosure The present invention provides a method of assessing the sustainability performance of an entity. This is achieved by monitoring the operation of the entity, and using this to determine one or more sustainability indicators, each sustainability indicator being a respective value determined based on the operation of the entity. The sustainability indicators are then compared to respective thresholds allowing the sustainability performance to be determined in accordance with the results of the comparison. |
1. (canceled). 2. (canceled). 3. (canceled). 4. (canceled). 5. (canceled). 6. (canceled). 7. (canceled). 8. (canceled). 9. (canceled). 10. (canceled). 11. (canceled). 12. (canceled). 13. (canceled). 14. (canceled). 15. (canceled). 16. (canceled). 17. (canceled). 18. (canceled). 19. (canceled). 20. (canceled). 21. (canceled). 22. (canceled). 23. (canceled). 24. (canceled). 25. (canceled). 26. (canceled). 27. (canceled). 28. (canceled). 29. (canceled). 30. (canceled). 31. (canceled). 32. (canceled). 33. (canceled). 34. (new): A method for assessing the sustainability performance of an entity, wherein the method comprises: a) monitoring an operation of the entity; b) selecting at least one sustainability indicator, wherein the sustainability indicator is measure of the operation of the entity in a particular environmental area; c) comparing the selected sustainability indicator to a first threshold, wherein the first threshold is a predetermined value representing a level of efficiency relative to the selected sustainability indicator; and, d) generating an indication of the sustainability performance in accordance with the results of the comparison. 35. (new): The method according to claim 35, wherein the sustainability indicator comprises at least one component value, and wherein the sustainability indicator that includes at least one component value is determined based on a weighted sum of the at least one component values. 36. (new): The method according to claim 35, wherein the sustainability indicator comprises at least one of: a) an energy indicator representing an amount of energy used by the entity; b) a water indicator representing an amount of water used by the entity; and, c) a waste indicator representing an amount of waste generated by the entity. 37. (new): The method according to claim 37, wherein the energy indicator comprises at least one energy component value, and wherein the energy component value represents the amount of energy used from an energy source. 38. (new): The method according to claim 38, wherein the energy indicator is determined by: a) determining an energy component based on the amount of energy used from a source; b) multiplying each energy component by a parameter to determine a modified component, wherein each parameter is predetermined in accordance with the energy source; and, c) summing each of the modified energy components. 39. (new): The method according to claim 35, wherein the sustainability indicator comprises at least one of: a) a social commitment indicator representing an impact of the entity on a local community; b) a resource conservation indicator representing an amount of ecological products used; and, c) a chemical indicator representing an amount of chemicals used. 40. (new): The method according to claim 40, wherein the social commitment indicator is a ratio of a number of employees of the entity living within a predetermined distance of the entity to a total number of employees of the entity. 41. (new): The method according to claim 40, wherein the resource conservation indicator is a ratio of a number of ecolabel products used to a total number of products used. 42. (new): The method according to claim 40, wherein the chemical indicator is a ratio of an amount of biodegradable chemicals used to a total amount of chemicals used. 43. (new): The method according to claim 35, wherein the sustainability indicator further comprises the presence and implementation of an environmental policy. 44. (new): The method according to claim 35, wherein in response to a successful comparison in which the selected sustainability indicator is greater than or equal to the first threshold, the method further comprises: a) comparing the sustainability indicator to a second threshold, wherein the second threshold is a predetermined value representing a level of efficiency greater than the level of efficiency represented by the first threshold; and, b) generating a second indication of the sustainability performance in accordance with the results of the second comparison. 45. (new): The method according to claim 35, wherein the method further comprises determining whether the comparison is successful, wherein a successful comparison is generated by the selected sustainability indicator being greater than or equal to the first threshold. 46. (new): The method according to claim 46, wherein the method further comprises certifying the entity in response to a successful comparison. 47. (new): The method according to claim 44, wherein the method further comprises: a) comparing the selected sustainability indicator to a second threshold, wherein the second threshold is a predetermined value representing a level of efficiency greater than the level of efficiency represented by the first threshold; and, b) determining whether the comparison of the sustainability indicator to the second threshold is successful, wherein a successful comparison is generated by the sustainability indicator being greater than or equal to the second threshold. 48. (new): The method according to claim 35, wherein the first threshold is determined in accordance with at least one of: a) a location of the entity; and, b) a nature of the entity's operation. 49. (new): The method according to claim 35, wherein the first threshold is determined in accordance with an average of the at least one selected sustainability indicator determined for a predetermined sample number of entities. 50. (new): The method according to claim 50, wherein the first threshold is 5% higher than the average of the at least one selected sustainability indicator. 51. (new): The method according to claim 50, wherein the first threshold is 30% higher than the average of the at least one selected sustainability indicator. 52. (new): The method according to claim 35, wherein the monitoring of the entity is performed by the entity or by a member of the entity. 53. (new): The method according to claim 35, wherein the monitoring of the entity is performed by an individual accredited by predetermined standards. 54. (new): The method according to claim 35, wherein the method further comprises generating a report, and wherein the report indicates the sustainability performance of the entity by indicating information comprising the results of the comparison. 55. (new): The method according to claim 55, wherein the report further indicates improvements that could be made to the operation of the entity to thereby enhance the sustainability performance of the entity. 56. (new): The method according to claim 35, wherein the method is performed using a processing system comprising: a) input means adapted to receive the selected sustainability indicator; b) memory means adapted to store data representative of the first threshold; and, c) a processor, wherein the processor is adapted to: i) compare the selected sustainability indicator to the first threshold; and, ii) generate the indication of the sustainability performance in accordance with the results of the comparison. 57. (new): The method according to claim 57, wherein the method further comprises causing the processor to store entity data in the memory means, and wherein the entity data comprises: a) an identity of the entity; and, b) the sustainability indicator. 58. (new): The method according to claim 58, wherein the entity data further comprises: a) a location of the entity; and, b) a nature of the entity's operation. 59. (new): The method according to claim 58, wherein the method further comprises determining the first threshold in accordance with the entity data stored in the store. 60. (new): A system for assessing the sustainability performance of an entity, wherein the system comprises: a) input means adapted to receive at least one sustainability indicator, wherein the sustainability indicator is a measure of the operation of the entity in a particular environmental area; b) memory means adapted to store a first threshold, wherein the first threshold is a predetermined value representing a level of efficiency relative to the sustainability indicator; and, c) a processor, wherein the processor is adapted to: i) compare the sustainability indicator to the first threshold; and, ii) generate an indication of the sustainability performance in accordance with the results of the comparison. 61. (new): The system according to claim 61, wherein the input means comprises a remote processing system coupled to the system via a communications network. 62. (new): The system according to claim 61, wherein the system further comprises a number of interconnected processing systems. 63. (new): A computer program product for assessing the sustainability performance of an entity, wherein the computer program product includes computer executable code which when executed by a suitably programmed processor causes the processor to perform the method of claim 35. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The present invention relates to a method of assessing the sustainability performance of an entity, and in particular, to a method of certifying entities that attain predetermined sustainability standards. |
<SOH> SUMMARY OF THE INVENTION <EOH>In a first broad form the present invention provides a method of assessing the sustainability performance of an entity, the method including: a) Monitoring the operation of the entity; b) Determining one or more sustainability indicators, each sustainability indicator being a respective value determined based on the operation of the entity; c) Comparing one or more of the sustainability indicators to respective thresholds; and, d) Generating an indication of the sustainability performance in accordance with the results of the comparison. The sustainability indicators generally include at least one of: a) An energy indicator representing the amount of energy used by the entity; b) A water indicator representing the amount of water used by the entity; and, c) A waste indicator representing the amount of waste generated by the entity. Other indicators can alternatively be used, and in general the indicators used will depend on the nature of the entity being assessed. Typically at least one of the sustainability indicators includes one or more component values, the sustainability indicator being determined based on a weighted sum of the component values. This is however not essential, and some indicators may be calculated directly, for example by measurement, or from utility bills, or the like. Thus, for example, the energy indicator can be formed from one or more energy component values, each energy component value representing the amount of energy used from a respective energy source. In this case, the method of determining the energy indicator typically includes: a) Determining a respective energy component based on the amount of energy used from a respective source; b) Multiplying each energy component by a respective parameter to determine a respective modified component, each parameter being predetermined in accordance with the respective energy source; and, c) Summing each of the modified energy components. The sustainability indicators may also include at least one of: a) A social commitment indicator representing the impact of the entity on the local community; b) A resource conservation indicator representing the amount of ecological products used; and, c) A pollution indicator representing the amount of pollution to air, water and land. In this case, the social commitment indicator may be a ratio of the number of employees living within a predetermined distance of the entity to the total number of employees. Alternatively, the social commitment indicator might be the amount of goods purchased locally as a percentage of total goods purchased. The resource conservation indicator is generally a ratio of the number of ecolabel products used to the total number of products used, while the pollution indicator might be a ratio of the amount of biodegradable chemicals used to the amount of non-biodegradable chemicals used. The sustainability indicators may also require at least the presence and implementation of a sustainability policy. Typically, in response to a successful comparison, the method further includes: a) Comparing one or more of the sustainability indicators to respective second thresholds; and, b) Generating a further indication of the sustainability performance in accordance with the results of the second comparison. The method usually includes: a) Comparing each indicator to a respective threshold; and, b) Determining that the entity satisfies minimum requirements in response to a successful comparison for each indicator. Typically each sustainability indicator is normalised relative to the size of the operation. Thus the sustainability indicators are typically calculated as either a ratio or per unit value, such as per guest at a hotel. In this case, the method preferably includes: a) Comparing each indicator to a normalised curve for this indicator; and, b) Recommending improvements for each indicator in terms of this normalised curve. The method preferably further includes certifying the entity in response to a successful determination. Thus, the entity typically has to satisfy a number of comparisons before it is determined that the entity satisfies minimum sustainability requirements, thereby qualifying for certification. However, alternatively, each comparison could be assessed independently, so that separate certification is based on each comparison. Alternatively, the indicator values could be combined and the assessment performed on the basis of a single threshold comparison. Typically the method includes: a) Comparing each indicator to a respective second threshold; and, b) Determining that the entity satisfies best practice requirements in response to a successful second comparison for each indicator. This allows different levels of certification to be provided. It will be appreciated that any number of levels of certification may be provided as desired. Each threshold is typically determined in accordance with at least one of: a) The entity's location; and, b) The nature of the entity's operation. This allows the certification to take into account environmental factors that are location or industry specific. For example the impact of electricity generation on the environment will differ depending on how the electricity is generated. Accordingly, the effect of using electricity from the National Grid will vary depending on the entity's location. The effect of this can be handled by setting thresholds based on factors, such as the location or nature of the entity. Each threshold may be determined in accordance with an average of the respective sustainability indicators determined for a sample number of entities, although other techniques, such as studying environmental reports, building environmental impact studies, recommendations from government or other organisations or the like. In the case in which averages are used, the threshold can be set 5% higher than the average of the respective sustainability indicators. This allows the system to ensure that the entity must be above average to get the minimum level of certification. In this case, the second threshold can be 30% higher than the average of the respective sustainability indicators, for example. The entity or a member of the entity may perform the monitoring. Alternatively, an accredited individual could perform the monitoring. However, generally a mixture of the two would be used, allowing for example, the member of the entity to do the initial assessment, with the accredited individual monitoring in future years. Typically the method further includes generating a report, the report indicating the sustainability performance of the entity by indicating at least the results of the comparisons. The report may also further indicate improvements that could be made to the operation to thereby the sustainability performance of the entity. Typically the method is performed using a processing system including at least: a) An input for receiving the one or more sustainability indicators; b) A store for storing the respective thresholds; and, c) A processor, the processor being adapted to: i) Compare the one or more of the sustainability indicators to respective thresholds; and, ii) Generate the indication of the sustainability performance in accordance with the results of the comparison. In this case, the method typically further includes causing the processor to store entity data in the store, the entity data representing at least: a) The identity of the entity; and, b) The sustainability indicators. The entity data may also further represent at least: c) The location of the entity; and, d) The nature of the entity's operation. The method can then include determining the thresholds in accordance with the entity data stored in the store. In a second broad form the present invention provides a system for assessing the sustainability performance of an entity, the system including: a) An input for receiving one or more sustainability indicators, each sustainability indicator being a respective value determined based on the operation of the entity; b) A store for storing respective thresholds; and, c) A processor, the processor being adapted to: i) Compare the one or more of the sustainability indicators to the respective thresholds; and, ii) Generate the indication of the sustainability performance in accordance with the results of the comparison. In this case, the input can be formed from a remote processing system coupled to the system via a communications network, although other forms of input could also be used. The system can also be formed from a number of interconnected processing systems. Typically the system is adapted to perform the method of the first broad form of the invention. In a third broad form the present invention provides a computer program product for assessing the sustainability performance of an entity, the computer program product including computer executable code which when executed by a suitably programmed processor causes the processor to perform the method of the first broad form of the invention. |
Water-soluble glass as corrosion protector in dishwashing machines |
A zinc-containing, water-soluble glass composition comprising from 41 to 54 mole % of P2O5, 10 to 30 mole % of alkali oxides, up to 5 mole % of SO3 and up to 25 mole % of ZnO. |
1. A zinc-containing, water-soluble glass composition comprising: from 41 to 54 mole % of P2O5, 10 to 30 mole % of alkali oxides, up to 5 mole % of SO3 and up to 25 mole % of ZnO. 2. The composition according to claim 1 characterised in that not more than 40 mole % of the total amount of alkali oxides in the composition is constituted by one or more members of the group consisting of Li2O and Na2O. 3. The composition according to claim 1 characterised in that the composition additionally comprises at least one alkaline-earth oxide with a total amount of alkaline-earth oxides of less than 20 mole %. 4. The composition according to claim 1 characterised in that the composition additionally comprises at least one oxide of antimony or arsenic present in the composition in an amount of of less than 5 mole %. 5. The composition according to claim 1 characterised in that the composition additionally comprises at least one oxide of an element from the group consisting of silicium, germanium, tin and lead present in the composition in an amount of with a total amount of such oxides of less than 10 mole %. 6. The composition according to claim 1 characterised in that the composition it additionally comprises at least one oxide of an element selected from the group consisting of silicon, aluminium and boron present in the composition in an amount of from 0. 1 to 10 mole. 7. The composition according to claim 1 characterised in that the composition does not comprise more than 0.5 mole-% of oxides of elements from the group IIIb of the Periodic System of Elements. 8. The composition according to claim 1 characterised in that the composition comprises from 41 to 54 mole % of P2O5, from 10 to 30 mole % of alkali oxides, up to 5 mole % of SO3, up to 25 mole % of ZnO, less than 5 mole % alkaline-earth oxides, and from 0.3 to 3 mole % of oxides of elements selected from the group consisting of silicon, aluminium and boron. 9. The composition according to claim 1 characterised in that the composition is present in the form of a transparent shaped body. 10. The composition according to claim 9 characterised in that the shaped body is manufactured by continuous glass manufacturing processes. 11. The composition according to claim 1 any of claims 1 to 8 characterised in that the composition it is present in a comminuted form. 12. The composition according to claim 11 characterised in that the composition is manufactured by the breaking of thin glass plates. 13. The composition according to claim 11 characterised in that the composition is manufactured by a process which includes a milling step. 14. The composition according to claim 13, characterised in that the milled glass has an average particle size of not more than 500 microns. 15. A process for the inhibition of corrosion of glassware in an automatic dishwashing process which comprises the step of: contacting said glassware with a zinc-containing, water-soluble glass composition according to claim 1. 16. A process for the inhibition of corrosion of glassware in an automatic dishwashing process characterised by: providing a zinc-containing, water-soluble glass composition according to claim 1 at an appropriate place within an automatic dishwashing machine wherein the said composition is accessible to the wash liquor and/or rinse water. 17. A process for the inhibition of corrosion of glassware in an automatic dishwashing process characterised by: contacting the glassware, in an automatic dishwashing machine, with wash liquor and/or rinse water containing an effective amount of a composition according to claim 1. 18. A process for the inhibition of corrosion of glassware in an automatic dishwashing process characterised by: providing a zinc-containing, water-soluble glass composition according to claim 9 at an appropriate place within an automatic dishwashing machine wherein the said composition is accessible to the wash liquor and/or rinse water. 19. A process for the inhibition of corrosion of glassware in an automatic dishwashing process characterised by: contacting the glassware, in an automatic dishwashing machine, with wash liquor and/or rinse water containing an effective amount of a composition according to claim 11. |
Location system and communication |
A location system comprises a plurality of transponders whose locations are detectable by a base system. The base system interrogates (51-55) the transponders one at a time in accordance with a schedule of consecutive time slots. In response to a priority request received (53) from one of the transponders, the base system interrupts the schedule and interrogates substantially immediately (56,57,55) the signalling transponder so as to determine its location with minimal latency. |
1.-18. (canceled) 19. A location system comprising a plurality of devices, each of whose locations is detectable, and a base system for detecting and registering the locations of the devices, the base system being arranged to interrogate the locations of the devices one at a time in a sequence of time slots so that the location of each device is repeatedly interrogated and to interrogate the location of any one of at least some of the devices substantially immediately in response to a radio signal from that same device, each of the devices comprising a transponder arranged to transmit an ultrasonic signal in response to receipt of a polling signal from the base system. 20. A location system as claimed in claim 19, in which the base system is arranged to interrogate the location of that same device in the first time slot to start after receipt of the signal from that same device. 21. A location system as claimed in claim 19, in which the signal from that same device is a manually actuable signal. 22. A location system as claimed in claim 19, in which the base system comprises a plurality of fixed ultrasonic transducers and a processor for determining the position of each device from the propagation times of ultrasonic energy from the device to each of at least some of the transducers. 23. A location system as claimed in claim 19, in which the polling signal is an electromagnetic signal. 24. A location system as claimed in claim 23, in which the electromagnetic signal is a radio signal. 25. A location system as claimed in claim 19, in which the location of each device is detectable anywhere within a predetermined region of space. 26. A location system comprising a plurality of devices, each of whose locations is detectable, and a base system for detecting and registering the locations of the devices, the base system being arranged to interrogate the locations of the devices one at a time in a sequence of time slots so that the location of each device is repeatedly interrogated and to interrogate the location of any one of at least some of the devices substantially immediately in response to a signal from that same device, the sequence of time slots being delayed by a time slot following the or each substantially immediate interrogation. 27. A location system as claimed in claim 26, in which the base system is arranged to interrogate the location of that same device in the first time slot to start after receipt of the signal from that same device. 28. A location system as claimed in claim 26, in which the signal from that same device is a manually actuable signal. 29. A location system as claimed in claim 26, in which the signal from that same device is an electromagnetic signal. 30. A location system as claimed in claim 29, in which the electromagnetic signal is a radio signal. 31. A location system as claimed in claim 26, in which each of the devices comprises a transponder arranged to transmit a response to receipt of a polling signal from the base system. 32. A location system as claimed in claim 31, in which the response is an ultrasonic signal. 33. A detection system as claimed in claim 32, in which the base system comprises a plurality of fixed ultrasonic transducers and a processor for determining the position of each device from the propagation times of ultrasonic energy from the device to each of at least some of the transducers. 34. A location system as claimed in claim 31, in which the polling signal is an electromagnetic signal. 35. A location system as claimed in claim 34, in which the electromagnetic signal is a radio signal. 36. A location system as claimed in claim 26, in which the location of each device is detectable anywhere within a predetermined region of space. 37. A location system comprising a plurality of devices, each of whose locations is detectable, and a base system for detecting and registering the locations of the devices, the base system being arranged to interrogate the locations of the devices one at a time in a sequence of time slots so that the location of each device is repeatedly interrogated and to interrogate the location of any one of at least some of the devices substantially immediately in response to a signal from that same device, the or each substantially immediate interrogation replacing interrogation of another of the devices which would have been interrogated in the absence of the signal from that same device. 38. A location system as claimed in claim 37, in which the base system is arranged to interrogate the location of that same device in the first time slot to start after receipt of the signal from that same device. 39. A location system as claimed in claim 37, in which the signal from that same device is a manually actuable signal. 40. A location system as claimed in claim 37, in which the signal from that same device is an electromagnetic signal. 41. A location system as claimed in claim 40, in which the electromagnetic signal is a radio signal. 42. A location system as claimed in claim 37, in which each of the devices comprises a transponder arranged to transmit a response to receipt of a polling signal from the base system. 43. A location system as claimed in claim 42, in which the response is an ultrasonic signal. 44. A detection system as claimed in claim 43, in which the base system comprises a plurality of fixed ultrasonic transducers and a processor for determining the position of each device from the propagation times of ultrasonic energy from the device to each of at least some of the transducers. 45. A location system as claimed in claim 42, in which the polling signal is an electromagnetic signal. 46. A location system as claimed in claim 45, in which the electromagnetic signal is a radio signal. 47. A location system as claimed in claim 37, in which the location of each device is detectable anywhere within a predetermined region of space. 48. An asynchronous time-division multiplex communication system comprising a scheduler for scheduling a plurality of messages for transmission and for transmitting substantially immediately a priority message in response to a request generated externally of the communication system. 49. A communication system as claimed in claim 48, in which the scheduler is arranged to transmit the priority message in a first time slot beginning after receipt of the request. 50. A communication system as claimed in claim 48, in which the priority message is generated externally of the communication system. 51. A communication system as claimed in claim 48, in which each message comprises a data packet having a header containing destination information. |
Anticancer agent |
An anticancer agent containing platinum preparation, humic substances, water and sodium chloride. Potassium tetrachloroplatinate is used as a platinum compound and lignohumic acid ammonium salts are used as humic substances taken in the following ratio of components per 1 ml of solution: lignohumic acid ammonium salts 0.18-0.22 mg potassium tetrachloroplatinate 0.020-0.040 mg sodium chloride isotonic solution 0.97-0.99 ml distilled water up to 1.0 ml |
1. An anticancer agent incorporating a platinum compound and sodium chloride, characterized in that the agent contains additional humic substances and water, using sodium chloride as a Na salt. 2. The anticancer agent according to claim 1, wherein potassium tetrachloroplatinate is used as a platinum compound and lignohumic acid ammonium salts are used as humic substances taken in the following ratio of components: lignohumic acid ammonium salts 0.18-0.22 mg potassium tetrachloroplatinate 0.020-0.040 mg sodium chloride isotonic solution 0.97-0.99 ml distilled water up to 1.0 ml. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Antineoplastic agents that incorporate platinum complexes attract specialists' attention featuring strong anti-tumor action, which causes violation of the mechanism of malignant cells gene action. Platinum preparations have a wide range of antineoplastic administration. Cis-dichlorodiammineplatinum (DDP), being the most thoroughly investigated agent of this anti-tumor group of agents, is active against tumors of various origins: spontaneous and inoculated ones, as well as those induced by viruses and chemical carcinogens. The DDP major drawback is connected with its high toxicity, which causes malfunction of kidneys, red marrow and the digestive tract. A certain antineoplastic agent (A, RU 2086261) is known to contain a platinum complex in the form of cis-diaminodichloro-trans-dihydroxyplatinum (IV) (oxoplatinum) at a rate of 10-25% and sodium bicarbonate and sodium alginete—at respective rates of 25-55% and 40-60%. This agent has been designed for oral administration in pills with the total weight of 0.35-0.60 g each. The therapeutic dose of the agent in question has 20 to 150 mg of platinum content. The medicine is active in treatment of a relatively wide range of malignant diseases and can be characterized by inhibition of metastases growth and zero nephrotoxic properties. Sodium bicarbonate, a component of the medicinal preparation, acts as a loosening agent with respect to the pill. When it gets into the gastric juice acid medium, the juice undergoes neutralization and carbon dioxide evolves. Gastric juice neutralization prevents substitution of oxoplatinum hydroxyl groups for chloro ligands to be accompanied with tetrachloride generation. Resulting in sodium chloride generation, interaction between hydrochloric acid sodium bicarbonate contributes to stabilization of chlorine ions in cis-diaminodichloro-trans-dihydroxyplatinum (IV). Selection of sodium alginete as a filling agent is connected with its high binding properties and with the fact that alginic acid generated due to its interaction with hydrochloric acid has good compatibility with living tissues. Thus, oxoplatinum acts as the only effective antineoplastic substance in the agent under consideration, which accounts for the necessity of relatively high dosage concerning its administration and increases the probability of complications associated with the toxicity of platinum preparations. In the course of research investigation of various platinum complexes on animals and clinical trials of DDP and some of its analogues a variety of biological features characteristic of platinum complexes were discovered: anti-tumor activity and respective side effects. It has been shown that insignificant changes in the molecular structure of the complex are capable of causing drastic changes in the above features with respect to bioactivity, including anti-tumor activity. Existing relationship between the complex structure and its anti-tumor activity encourages the search for new platinum-containing agents featuring both high activity and low toxicity. |
<SOH> SUMMARY OF THE INVENTION <EOH>The aim of the present invention is to create such an anticancer agent which would incorporate platinum compounds of relatively low concentration and bioactive agents, and therefore would ensure both reduced toxicity of the agent and enhanced effectiveness of treatment of malignant diseases. The set task is solved in such a manner that the medicinal preparation contains additional humic substances and water along with platinum compounds and Na salts, sodium chloride being used as a Na salt. The proposed anticancer agent is a combined preparation containing both inorganic substances (platinum compounds) and organic bioactive components (humic substances). Platinum compounds feature marked anti-tumor activity. Acting as the preparation organic components, humic substances represent a large group of natural compounds. Their origin is connected with the hydrolytic decay of wood lignin. Entering into the composition of humic substances, humic acids are active components of some pharmaceuticals related to a biogenic stimulants group (e.g. Humisol, Befungin, and the like). The sodium chloride aqueous solution ensures isotonicity of the preparation medium with the medium of a living body, which enables intramuscular administration of the agent, for example. In the course of the research it has been discovered that the complex medicinal preparation containing the platinum preparation and humic substances demonstrates a synergetic increase in activity (shown in an example below). It is advisable to use lignohumic acid ammonium salts as humic substances and potassium tetrachloroplatinate as a platinum compound; it is expedient to use a Na salt in the form of sodium chloride isotonic solution in the following ratio of components per 1 ml of solution: lignohumic acid ammonium salts 0.18-0.22 mg potassium tetrachloroplatinate 0.020-0.040 mg sodium chloride isotonic solution 0.97-0.99 ml distilled water up to 1.0 ml The ratio of the proposed preparation components was chosen experimentally on grounds of maximum effectiveness under low toxicity conditions. Platinum content in a therapeutic dose amounts to 0.008-0.0010 mg, being significantly lower than in any of the known medicinal preparations. Therefore, toxic action of the proposed preparation should be many times as low. It has been experimentally demonstrated that with the decreasing proportion of lignohumic acid salts the preparation effectiveness reduces due to the lower stability of the platinum complex; a therapeutic effect does not intensify with the increasing proportion of lignohumic acid salts. Thus, the upper limit of the lignohumic acid salts content ensures the preparation maximum effectiveness. A reduction in the potassium tetrachloroplatinate content causes a decrease in the therapeutic effect. Where the potassium tetrachloroplatinate content exceeds the specified amount, the compound stability occurs, toxicity grows and the therapeutic effect decreases. The sodium chloride solution ensures isotonicity of the preparation medium with the medium of a living body, which enables intramuscular administration of the agent, for example. The amount of the sodium chloride solution is determined on the basis of conformity between the preparation osmotic pressure and the osmotic pressure of blood plasma. Water is used as a dissolving agent. The lignohumic acid salts entering into the composition of the proposed agent can be generated by liquid-phase oxidation of hydrolytic lignin with molecular oxygen in the alkaline medium (RU, A, 93037252). detailed-description description="Detailed Description" end="lead"? |
Method for producing hydrogen gas |
A monometal (1) is contacted with deuterated acidic water solution (2) in which at least some of hydrogen atoms contained in acidic water solution are substituted for deuterium atoms, thereby to generate hydrogen gas. With this, a great amount of hydrogen gas can be generated in a short period of time. |
1. A method for producing hydrogen gas, comprising the step of contacting a monometal with deuterated acidic water solution in which at least some of hydrogen atoms contained in acidic water solution are substituted for deuterium atoms, thereby to generate hydrogen gas. 2. The method for producing hydrogen according to claim 1, wherein said acidic water solution contains at least one kind of acid selected from the group consisting of citric acid, glycine, cinnamic acid, succinic acid, salicylic acid, formic acid, glutamic acid, ascorbic acid, oxalic acid, tartaric acid, lactic acid, acetic acid, sulfuric acid, hydrochloric acid, and nitric acid. |
<SOH> BACKGROUND ART <EOH>Hydrogen gas can be generated by e.g. immersing metal in acidic water solution. The sole conventional concept was generating hydrogen gas by immersing metal in acidic water solution comprising normal water and an acid component. With the above-described conventional method, however, the generation rate of hydrogen is low and it is not possible to generate a large amount of hydrogen gas in a short period of time. Hence, this method requires room for improvement, if it is to be put into actual use for supplying various kinds of hydrogen gas. The present invention has been made in view of the above-described state of the art. The primary object of the invention is to provide a method for producing hydrogen gas which method allows a great amount of hydrogen gas to be generated in a short period of time. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is an explanatory view in partial section showing an example of contacting condition between a deuterated acidic water solution and a monometal, FIG. 2 is a graph showing changes over time in the hydrogen generation amount in comparison between a case using the deuterated sulfuric acid water solution and Mg metal and a further case using standard sulfuric acid water solution for industrial use and the Mg metal, FIG. 3 is a graph showing hydrogen gas generation amounts per a predetermined unit time in comparison between the case using the deuterated sulfuric acid water solution and Mg metal and the further case using standard sulfuric acid water solution for industrial use and the Mg metal, FIG. 4 is a graph showing hydrogen gas generation amounts per a predetermined unit time in comparison between the case using the deuterated sulfuric acid water solution and Mg metal and a further case using the deuterated sulfuric acid water solution and Zn metal, FIG. 5 is an explanatory view in partial section showing an example of contacting condition between a deuterated acidic water solution and a monometal relating to a further embodiment, FIG. 6 is a graph showing the hydrogen generation amount relating to a still further embodiment, FIG. 7 is a graph showing pH variation in the deuterated sulfuric acid water solution relating to a still further embodiment, and FIG. 8 a graph showing the hydrogen generation amount relating to a still further embodiment. detailed-description description="Detailed Description" end="lead"? |
Enanitomers of unsaturated alkyllysophosphonocholines and use as anti-neoplastics |
Unsaturated alkyllysophosphonocholines compounds of formula (I) or (II): or pharmaceutically-acceptable salts, prodrugs or isomers thereof. The compounds of the invention have anti-neoplastic activity, and accordingly have utility in treating cancer and related diseases. The invention also provides enantiomers of these compounds, as well as synthetic methods for producing an enantiomer, substantially free of the other enantiomer. Also disclosed are pharmaceutical compositions, as well methods for treating cancer with the pharmaceutical compositions. |
1. A compound of the formula I, or a pharmaceutically acceptable salt, prodrug or isomer thereof: wherein X1 is H, R1, R2, OR2, NR1R2, or S(O)aR2, where a is an integer selected from 0, 1, 2, or 3; X2 is H, R3, R4, OR4, NR3R4, or S(O)aR4, where a is an integer selected from 0, 1, 2, or 3; X3 is (CH2)b, where b is an integer selected from 0, 1, 2, 3, or 4; X4 is (CH2)c, where c is an integer selected from 0, 1, 2, 3, or 4; R1 is a straight-chain or branched alkyl having 12 to 20 carbon atoms or a straight-chain or branched alkenyl group having 12 to 20 carbon atoms; R2 is H, a straight-chain or branched alkyl having 12 to 20 carbon atoms or a straight-chain or branched alkenyl group having 12 to 20 carbon atoms; R3 is a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R4 is H, a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R5 is (CH2)m where m is an integer selected from 0, 1, 2, 3, or 4; Z is H, X5 is N or As; R6 and R7 are each independently hydrogen, a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; and R8 is hydrogen, a straight-chain alkyl group having 1 to 3 carbon atoms or a branched or cyclic alkyl group having 3 carbon atoms. 2. The compound of claim 1 further comprising a pharmaceutically acceptable anion. 3. The compound of claim 1, wherein R1 and R2 are each independently a straight-chain or branched alkyl having 16 to 20 carbon atoms, or a straight-chain or a branched alkenyl group having 16 to 20 carbon atoms. 4. The compound of claim 3, wherein R1 and R2 are each independently a straight-chain or branched alkyl having 18 carbon atoms, or a straight-chain or a branched alkenyl group having 18 carbon atoms. 5. The compound of claim 1, wherein X1 is OR2 or NHR2, and wherein R2 is a straight-chain or branched alkyl having 16 to 20 carbon atoms, or a straight-chain or a branched alkenyl group having 16 to 20 carbon atoms. 6. The compound of claim 5, wherein X1 is OR2 or NHR2, and wherein R2 is a straight-chain or branched alkyl having 18 carbon atoms, or a straight-chain or a branched alkenyl group having 18 carbon atoms. 7. The compound of claim 1, wherein X1 or X2 is —SR2. 8. The compound of claim 1, wherein X_or X2 is —S(═O)R2. 9. The compound of claim 1, wherein X1 or X2 is —S(═O)2R2. 10. The compound of claim 1, wherein X1 or X2 is —S(═O)2OR2. 11. The compound of claim 1, wherein X1 or X2 is —OS(═O)2R2. 12. The compound of claim 1 wherein X1 or X2 is —OCH3. 13. The compound of claim 1, wherein X3, X4, and R5 are each independently a direct link, a —CH2— group, or a —CH2CH2— group. 14. The compound of claim 1, wherein Z is 15. The compound of claim 1, wherein Z is 16. The compound of claim 1, wherein X1 is O, X2 is O, X4 is O and b is 0. 17. The compound of claim 1, wherein the compound is optically active, and substantially free of the R enantiomer. 18. The compound of claim 1, wherein the compound is optically active and substantially free of the S enantiomer. 19. The compound of claim 1, wherein the compound is 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate substantially free of the R enantiomer. 20. The compound of claim 1, wherein the compound is 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate substantially free of the S enantiomer. 21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 1. 22. A method of treating a mammal afflicted with a cancer which comprises administering to the mammal a therapeutically effective amount of the pharmaceutical composition of claim 21, comprising from about 0.1 to about 1000 mg of the compound of claim 1 per kg of the body weight of the mammal per day. 23. A method of claim 22, wherein the cancer is selected from the group consisting of lung cancers, brain cancers, colon cancers, ovarian cancers, breast cancers, leukemias, lymphomas, sarcomas, and carcinomas. 24. The method of claim 22, comprising administering to the mammal an additional biologically active agent. 25. The method of claim 24, wherein the additional biologically active agent is selected from the group consisting of antineoplastic agents, antimicrobial agents, and hematopoietic cell growth stimulating agents. 26. A compound of formula II, or a pharmaceutically acceptable salt, prodrug or isomer thereof: wherein X1 is H, R1, R2, OR2, NR1R2, or S(O)aR2, where a is an integer selected from 0, 1, 2, or 3; X2 is H, R3, R4, OR4, NR3R4, or S(O)aR4, where a is an integer selected from 0, 1, 2, or 3; X3 is (CH2)b, where b is an integer selected from 0, 1, 2, 3, or 4; X4 is (CH2)c, where c is an integer selected from 0, 1, 2, 3, or 4; R1 is a straight-chain or branched alkyl having 12 to 20 carbon atoms or a straight-chain or branched alkenyl group having 12 to 20 carbon atoms; R2 is H, a straight-chain or branched alkyl having 12 to 20 carbon atoms or a straight-chain or branched alkenyl group having 12 to 20 carbon atoms; R3 is a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R4 is H, a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R5 is (CH2)m where m is an integer selected from 0, 1, 2, 3, or 4; Z is H, X5 is N or As; R6 and R7 are each independently hydrogen, a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R8 is hydrogen, a straight-chain alkyl group having 1 to 3 carbon atoms or a branched or cyclic alkyl group having 3 carbon atoms; and R9 is a straight-chain alkyl group having 1 to 3 carbon atoms or a branched or cyclic alkyl group having 3 carbon atoms. 27. The compound of claim 26 further comprising a pharmaceutically acceptable anion. 28. The compound of claim 26, wherein R1 and R2 are each independently a straight-chain or branched alkyl having 16 to 20 carbon atoms, or a straight-chain or a branched alkenyl group having 16 to 20 carbon atoms. 29. The compound of claim 28, wherein R1 and R2 are each independently a straight-chain or branched alkyl having 18 carbon atoms, or a straight-chain or a branched alkenyl group having 18 carbon atoms. 30. The compound of claim 26, wherein X1 is OR2 or NHR2, and wherein R2 is a straight-chain or branched alkyl having 16 to 20 carbon atoms, or a straight-chain or a branched alkenyl group having 16 to 20 carbon atoms. 31. The compound of claim 30, wherein X1 is OR2 or NHR2, and wherein R2 is a straight-chain or branched alkyl having 18 carbon atoms, or a straight-chain or a branched alkenyl group having 18 carbon atoms. 32. The compound of claim 26, wherein X1 or X2 is —SR2. 33. The compound of claim 26, wherein X1 or X2 is —S(═O)R2. 34. The compound of claim 26, wherein X1 or X2 is —S(═O)2R2. 35. The compound of claim 26, wherein X1 or X2 is —S(═O)2OR2. 36. The compound of claim 26, wherein X1 or X2 is —OS(═O)2R2. 37. The compound of claim 26, wherein X2 is —OCH3. 38. The compound of claim 26, wherein X3, X4, and R5 are each independently a direct link, a —CH2— group, or a —CH2CH2— group. 39. The compound of claim 26, wherein Z is 40. The compound of claim 26, wherein Z is 41. The compound of claim 26, wherein X1 is O, X2 is O, X4 is O and b is 0. 42. The compound of claim 26, wherein the compound is optically active, and substantially free of the R enantiomer. 43. The compound of claim 26, wherein the compound is optically active and substantially free of the S enantiomer. 44. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 43. 45. A method of treating a mammal afflicted with a cancer which comprises administering to the mammal a therapeutically effective amount of the pharmaceutical composition of claim 44, comprising from about 0.1 to about 1000 mg of the compound of claim 1 per kg of the body weight of the mammal per day. 46. A method of claim 45, wherein the cancer is selected from the group consisting of lung cancers, brain cancers, colon cancers, ovarian cancers, breast cancers, leukemias, lymphomas, sarcomas, and carcinomas. 47. The method of claim 46, comprising administering to the mammal an additional biologically active agent. 48. The method of claim 47, wherein the additional biologically active agent is selected from the group consisting of antineoplastic agents, antimicrobial agents, and hematopoietic cell growth stimulating agents. 49. A method for making 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate substantially free of the (R) enantiomer, comprising: (i) oxidizing 1-O-hexadecyl-2-O-methyl-sn-glycerol under Swern oxidation conditions sufficient to produce (S)-1-O-hexadecyl-2-O-methoxyglyceraldehyde; (ii) reacting the (S)-1-O-hexadecyl-2-O-methoxyglyceraldehyde with tetraisopropyl methylenediphosphonate under conditions sufficient to produce diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate; (iii) hydrolyzing the diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate under conditions sufficient to produce the 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonic acid; and (iv) reacting the diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate with choline tosylate under conditions sufficient to produce 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate. 50. A method for making 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate substantially free of the (S) enantiomer, comprising: (i) oxidizing 3-O-hexadecyl-2-O-methyl-sn-glycerol under Swern oxidation conditions sufficient to produce (S)-1-O-hexadecyl-2-O-methoxyglyceraldehyde; (ii) reacting the (S)-1-O-hexadecyl-2-O-methoxyglyceraldehyde with tetraisopropyl methylenediphosphonate under conditions sufficient to produce diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate; (iii) hydrolyzing the diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate under conditions sufficient to produce the 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonic acid; and (iv) reacting the diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate with choline tosylate under conditions sufficient to produce 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The present invention provides novel unsaturated alkyllysophosphonocholines compounds and enantiomers thereof, as well as pharmaceutical compositions thereof, and methods for treating cancer. Synthetic methods for synthesizing enantiomers of the compounds is also provided. 2. State of the Art Alkyllysophospholipids (ALPs) and alkylphosphocholines (APCs) represent subclasses of potential antitumor agents collectively known as antitumor ether lipids (AELs). They do not interact with cellular DNA and are therefore not mutagenic (Berdel, W. E. (1991) Br. J Cancer, 64, 208-211; Lohmeyer, M., and Bittman, R. (1994) Drugs of the Future 19, 1021-1037). The antitumor activities of these compounds, which are based on lysophosphatidylcholine, are now well established; the prototype of the alkyllysophospholipids (ALPs), 1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OCH 3 ), and other ether-linked phosphocholine analogues are in clinical trials (Lohmeyer, M., and Bittman, R. (1994) Drugs of the Future 19, 1021-1037, Houlihan, W. J., Lohmeyer, M., Workman, P., and Cheon, S. H. (1995) Med Res. Rev. 15, 157-223; Principe, P., and Braquet, P. (1995) Rev. Oncol. Hematol. 18, 155-178). ALPs also appear to inhibit the proliferation of tumor cells without affecting the growth of normal cells (Berdel, W. E., Andreesen, R., and Munder, P. G. (1985) in Phospholipids and Cellular Regulation, Vol 2. Kuo, J (ed). CRC Press: Boca Raton, pp. 41-73). While the mechanism of inhibition of cell proliferation has yet to be resolved, various hypotheses have been proposed. In some cells, ALPs and APCs appear to induce apoptosis as a consequence of inhibition of phosphatidylcholine synthesis (Boggs, K. P., Rock, C. O., and Jackowski, S. (1995) J Biol. Chem. 270, 11612-11618; Boggs, K. P., Rock, C. O., and Jackowski, S. (1998) Biochim. Biophys. Acta 1389, 1-12); activation of the stress activated protein kinase pathways (Gajate, C., Santos-Beneit, A., Modolell, M., and Mollinedo, F. (1998) Mol. Pharmacol. 53, 602-612; Ruiter, G. A., Zerp, S. F., Bartelink, H., Van Blitterswijk, W. J., and Verheij, M. (1999) Cancer Res. 59, 2457-2463), drug-induced increase in cellular cerarnide levels (Wieder, T., Orfanos, C. E., and Geilen, C. G. (1998) J. Biol. Chem. 273, 11025-11031); nutrient starvation, inhibition of transacylase activity, enhanced lipid peroxidation and inhibition of cellular signaling pathways (reviewed in Bittman, R., and Arthur, G. (1998) in A. S. Janoff (ed.), Liposomes: Rational Design, pp 125-144, New York: Marcel Dekker; Arthur; G., and Bittman, R. (1998) Biochim. Biophys. Acta 1390, 85-102). Other studies have revealed that ALPs affect the activity of a large number of signaling molecules including protein kinase C (PKC), phosphatidylinositol 3-kinase, phosphatidylinositol-specific phospholipase C, and diacylglycerol kinase (reviewed in Arthur, G., and Bittman, R. (1998) Biochim. Biophys. Acta 1390, 85-102). Recently another signaling molecule, Raf-1, was added to the list with the demonstration that ET-18-OCH 3 decreased the levels of Raf-1 associating with the cell membrane in growth-factor stimulated MCF-7 cells which consequently led to decreased activation of MAP kinase (Zhou, X., Lu, X., Richard, C., Xiong, W., Litchfield, D. W., Bittman, R., and Arthur, G. (1996) J Clin. Invest. 98, 937-944), a crucial enzyme required in initiating cell proliferation (Marshall, C. J. (1995) Cell 80, 179-185). It was suggested that Raf-1 is a primary target of ALPs in cells. The large number of molecules affected by ALPs has complicated the task of separating their primary site(s) of action from secondary events. In order to advance the present understanding of the mechanism(s) of action of these compounds, one has to distinguish target molecules and events that are relevant to growth inhibition from those that are irrelevant. Despite the progress that has been made in understanding the underlying mechanisms of antitumor ether lipids, there remains a need to develop novel compounds and compositions for treatment of disease. Ideally, the treatment methods would advantageously be based on anti-tumor ether lipids that are capable of acting as anti-neoplastic agents. |
<SOH> SUMMARY OF THE INVENTION <EOH>The invention is directed to the discovery of a class of anti-tumor ether lipid compounds having anti-neoplastic activity. Preferably, the invention provides bioactive unsaturated alkyllysophosphonocholines or pharmaceutically-acceptable salts, prodrugs or isomers thereof having the R or S configuration at the C-2 position of the glycerol backbone. The invention also relates to pharmaceutical compositions comprising these compounds, and methods for treating cancer. Neither the R enantiomer nor S enantiomer of a trans double bond (TBD) phosphonocholine etherlipid, an analogue of ET-16-OCH 3 , 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-methoxy-1-butenephosphonate [ET-16-phosphono-TDB], has previously been synthesized. In order to differentiate the activities of each of these enantiomers, single enantiomers must be available in sufficient chiral purity to enable a comparison of the chemical, biological and biochemical effects of the single enantiomers. Thus, until the present invention nothing was known about the antineoplastic effects of the single R and S enantiomers of phosphono etherlipids, in general, and ET-16-phosphono-TDB specifically. In one embodiment, the invention relates to compounds, or a pharmaceutically acceptable salt, prodrug or isomer thereof, having formula I below: wherein X 1 is H, R 1 , R 2 , OR 2 , NR 1 R 2 , or S(O) a R 2 , where a is an integer selected from 0, 1, 2, or 3; X 2 is H, R 3 , R 4 , OR 4 , NR 3 R 4 , or S(O) a R 4 , where a is an integer selected from 0, 1, 2, or 3; X 3 is (CH 2 ) b , where b is an integer selected from 0, 1, 2, 3, or 4; X 4 is (CH 2 ) c , where c is an integer selected from 0, 1, 2, 3, or 4; R 1 is a straight-chain or branched alkyl having 12 to 20 carbon atoms or a straight-chain or branched alkenyl group having 12 to 20 carbon atoms; R 2 is H, a straight-chain or branched alkyl having 12 to 20 carbon atoms or a straight-chain or branched alkenyl group having 12 to 20 carbon atoms; R 3 is a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R 4 is H, a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R 5 is (CH 2 ) m where m is an integer selected from 0, 1, 2, 3, or 4; Z is H, X 5 is N or As; R 6 and R 7 are each independently hydrogen, a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; and R 8 is hydrogen, a straight-chain alkyl-group having 1 to 3 carbon atoms or a branched or cyclic alkyl group having 3 carbon atoms. In another embodiment, the invention relates to compounds of formula II, or a pharmaceutically acceptable salt, prodrug or isomer thereof: wherein X 1 is H, R 1 , R 2 , OR 2 , NR 1 R 2 , or S(O) a R 2 , where a is an integer selected from 0, 1, 2, or 3; X 2 is H, R 3 , R 4 , OR 4 , NR 3 R 4 , or S(O) a R 4 , where a is an integer selected from 0, 1, 2, or 3; X 3 is (CH 2 ) b , where b is an integer selected from 0, 1, 2, 3, or 4; X 4 is (CH 2 ) c , where c is an integer selected from 0, 1, 2, 3, or 4; R 1 is a straight-chain or branched alkyl having 12 to 20 carbon atoms or a straight-chain or branched alkenyl group having 12 to 20 carbon atoms; R 2 is H, a straight-chain or branched alkyl having 12 to 20 carbon atoms or a straight-chain or branched alkenyl group having 12 to 20 carbon atoms; R 3 is a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R 4 is H, a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R 5 is (CH 2 ) m where m is an integer selected from 0, 1, 2, 3, or 4; Z is H, X 5 is N or As; R 6 and R 7 are each independently hydrogen, a straight-chain alkyl group having 1 to 3 carbon atoms, or a branched or cyclic alkyl group having 3 carbon atoms; R 8 is hydrogen, a straight-chain alkyl group having 1 to 3 carbon atoms or a branched or cyclic alkyl group having 3 carbon atoms; and R 9 is a straight-chain alkyl group having 1 to 3 carbon atoms or a branched or cyclic alkyl group having 3 carbon atoms. The compounds of formula (I) or (II) above may further comprise a pharmaceutically acceptable anion. Preferably, R 1 and R 2 are independently a straight-chain or branched alkyl having 16 to 20 carbon atoms, or a straight-chain or a branched alkenyl group having 16 to 20 carbon atoms. In another preferred embodiment, R 1 and R 2 are independently a straight-chain or branched alkyl having 18 carbon atoms, or a straight-chain or a branched alkenyl group having 18 carbon atoms. In an embodiment of the invention, X 1 is OR 2 or NHR 2 , where R 2 is a straight-chain or branched alkyl having 16 to 20 carbon atoms, or a straight-chain or a branched alkenyl group having 16 to 20 carbon atoms. In a preferred embodiment, R 2 is a straight-chain or branched alkyl having 18 carbon atoms, or a straight-chain or a branched alkenyl group having 18 carbon atoms. In an embodiment of the invention, X 1 or X 2 is independently selected from —SR 2 , —S(═O)R 2 , —S(═O) 2 R 2 , —S(═O) 2 OR 2 , or —OS(═O) 2 R 2 . In an embodiment of the invention, X 1 or X 2 is —OCH 3 . Typical values for X 3 , X 4 , and R 5 include a direct link, a —CH 2 — group, or a —CH 2 CH 2 — group. Preferred values for Z include Yet another embodiment of the invention relates to compounds where X 1 is O, X 2 is O, X 4 is O and b is 0. The invention also relates to optically active compounds of formula (I) or (II), which are substantially free of the R enantiomer. In addition, the invention also relates to optically active compounds of formula (I) or (II), which are substantially free of the S enantiomer. For example, the invention relates to 2′-(trimethylanmmonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate substantially free of the R enantiomer, as well as 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate substantially free of the S enantiomer. Additionally, the invention relates to pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of formula (I) or (II). These pharmaceutical compositions can be used in methods for treating a mammal afflicted with a cancer, comprising administering to the mammal a therapeutically effective amount of the pharmaceutical composition. Typical dosages range from about 0.1 to about 1000 mg of the compound of formula (I) or (II) per kg of the body weight of the mammal per day. The type of cancer to be treated may be selected from the group consisting of, but not limited to: lung cancers, brain cancers, colon cancers, ovarian cancers, breast cancers, leukemias, lymphomas, sarcomas, and carcinomas. These treatment methods may also include administering to the mammal an additional biologically active agent. The additional biologically active agent may be selected from the group consisting of antineoplastic agents, antimicrobial agents, and hematopoietic cell growth stimulating agents, for example. In addition, the invention relates to a method for making 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate substantially free of the (R) enantiomer, comprising: (i) oxidizing 1-O-hexadecyl-2-O-methyl-sn-glycerol under Swern oxidation conditions sufficient to produce (S)-1-O-hexadecyl-2-O-methoxyglyceraldehyde; (ii) reacting the (S)-1-O-hexadecyl-2-O-methoxyglyceraldehyde with tetraisopropyl methylenediphosphonate under conditions sufficient to produce diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate; (iii) hydrolyzing the diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate under conditions sufficient to produce the 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonic acid; and (iv) reacting the diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate with choline tosylate under conditions sufficient to produce 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate. The invention also relates to a method for making 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate substantially free of the (S) enantiomer, comprising: (i) oxidizing 3-O-hexadecyl-2-O-methyl-sn-glycerol under Swern oxidation conditions sufficient to produce (S)-1-O-hexadecyl-2-O-methoxyglyceraldehyde; (ii) reacting the (S)-1-O-hexadecyl-2-O-methoxyglyceraldehyde with tetraisopropyl methylenediphosphonate under conditions sufficient to produce diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate; (iii) hydrolyzing the diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate under conditions sufficient to produce the 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonic acid; and (iv) reacting the diisopropyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate with choline tosylate under conditions sufficient to produce 2′-(trimethylammonio)ethyl 4-(hexadecyloxy)-3-(S)-methoxy-1-butenephosphonate. |
Rear cover assembly for washing machine and dryer and washing system using the same |
Rear cover assemblies (100, 200) for washing machines and dryers including front panels(110, 210) each mounted on rear of a top cover fitted to an upper part of each of the washing machines (1) and the dryers (2), the front panels each having a seat (111, 211) of identical shape, and back panels (120, 210) each being formed to be fitted to the seat (111, 211) of the front panel (110, 210), the back panel being configured to allow accessories required for each of the washing machines (1) or each of the dryers (2) to be fitted thereto. These rear cover assemblies form a unified particular outer appearance in one set consisting of any selected two of the washing machines (1) and the dryers (2), and they are exchangeable such that the particular outer appearance can be maintained even if relative positions of the washing machines and the dryers within the one set are changed. |
1. Rear cover assemblies for washing machines and dryers comprising: front panels each mounted on rear of a top cover fitted to an upper part of each of the washing machines and the dryers, the front panels each having a seat of identical shape; and back panels each being formed to be fitted to the seat of the front panel, the back panels be configured to allow accessories required for each of the washing machines or each of the dryers to be fitted thereto, wherein the rear cover assemblies form a unified particular outer appearance in one set consisting of any selected two of the washing machines and the dryers, and the rear cover assemblies are exchangeable in the one set such that the particular outer appearance can be maintained for the one set even if relative positions of the washing machines and the dryers within the one set are changed. 2. The rear cover assemblies as claimed in claim 1, wherein the particular outer appearance is formed by the front panels. 3. The rear cover assemblies as claimed in claim 2, wherein the particular outer appearance is formed by upper part outlines of the front panels. 4. The rear cover assemblies as claimed in claim 2, wherein the front panels are symmetric within the one set. 5. The rear cover assemblies as claimed in claim 1, wherein the front panel includes a control panel enabling a user to operate the washing machine or the dryer. 6. The rear cover assemblies as claimed in claim 5, wherein the control panel includes various buttons for giving operational orders and a display window for displaying an operation state. 7. The rear cover assemblies as claimed in claim 5, wherein the control panel is unified with the front panel, or detachable from the front panel. 8. The rear cover assemblies as claimed in claim 7, wherein the windows and buttons have identical positions in the different control panels in the one set. 9. The rear cover assemblies as claimed in claim 1, wherein the seat is formed by cutting off a rear surface of the front panel. 10. The rear cover assemblies as claimed in claim 1, wherein the accessories for the washing machine include a water supply tube and wires. 11. The rear cover assemblies as claimed in claim 1, wherein the accessories for the dryer include wire. 12. The rear cover assemblies as claimed in claim 1, wherein the back panel of the dryer is formed of a metal. 13. The rear cover assemblies as claimed in claim 1, wherein the back panel is formed unified with the top cover. 14. A washing machine comprising: a cabinet; a washing tub, or drum mounted in the cabinet rotatable by power means for washing laundry; a top cover for covering an upper part of the cabinet; and a rear cover including; a front panel mounted in a rear part of the top cover and having a seat of a predetermined shape, and a back panel configured to allow various accessories to be fitted thereto, the back panel being formed to be fitted to the seat in the front panel, wherein, when the washing machine is combined with another washing machine or a dryer having identical rear cover, the rear covers form a unified particular outer appearance, and the rear covers are exchangeable such that the particular outer appearance is maintained even if positions of the washing machine and the another washing machine or the dryer are interchanged. 15. The washing machine as claimed in claim 14, wherein the particular outer appearance is formed by the front panels. 16. The washing machine as claimed in claim 15, wherein the particular outer appearance is formed by upper part outlines of the front panels. 17. The washing machine as claimed in claim 15, wherein the front panels are symmetric. 18. The washing machine as claimed in claim 14, wherein the front panel includes a control panel enabling a user to operate the washing machine. 19. The washing machine as claimed in claim 18, wherein the control panel includes various buttons for giving operational orders and a display window for displaying an operation state. 20. The washing machine as claimed in claim 18, wherein the control panel is unified with the front panel, or detachable from the front panel. 21. The washing machine as claimed in claim 20, wherein the windows and buttons have identical positions in the different control panels. 22. The washing machine as claimed in claim 14, wherein the seat is formed by cutting off a rear surface of the front panel. 23. The washing machine as claimed in claim 14, wherein the accessories include a water supply tube and wires. 24. The washing machine as claimed in claim 14, wherein the back panel is formed unified with the top cover. 25. A dryer comprising: a cabinet; a drum mounted in the cabinet rotatable by power means for drying laundry; a top cover for covering an upper part of the cabinet; and a rear cover including; a front panel mounted in a rear part of the top cover and having a seat of a predetermined shape, and a back panel be configured to allow various accessories to be fitted thereto, the back panel being formed to be fitted to the seat in the front panel, wherein when the dryer is combined with another dryer or a washing having identical rear cover, the rear covers form a unified particular outer appearance, and the rear covers are exchangeable such that the particular outer appearance is maintained even if positions of the dryer and the another dryer or the washing machine are interchanged. 26. The dryer as claimed in claim 25, wherein the particular outer appearance is formed by the front panels. 27. The dryer as claimed in claim 26, wherein the particular outer appearance is formed by upper part outlines of the front panels. 28. The dryer as claimed in claim 26, wherein the front panels are symmetric. 29. The dryer as claimed in claim 25, wherein the front panel includes a control panel enabling a user to operate the dryer. 30. The dryer as claimed in claim 29, wherein the control panel includes various buttons for giving operational orders and a display window for displaying an operation state. 31. The dryer as claimed in claim 29, wherein the control panel is unified with the front panel, or detachable from the front panel. 32. The dryer as claimed in claim 31, wherein the windows and buttons have identical positions in the different control panels. 33. The dryer as claimed in claim 25, wherein the seat is formed by cutting off a rear surface of the front panel. 34. The dryer as claimed in claim 25, wherein the accessories include wires. 35. The dryer as claimed in claim 25, wherein the back panel is formed of a metal. 36. The dryer as claimed in claim 25, wherein the back panel is formed unified with the top cover. 37. A washing system comprising: a washing machine including a cabinet, a washing tub or drum mounted in the cabinet rotatable by power means for washing laundry, a top cover for covering an upper part of the cabinet, and a rear cover having a front panel mounted in a rear part of the top cover and having a seat of a predetermined shape and a back panel configured to allow various accessories to fitted thereto and formed to be fitted to the seat in the front panel; and a dryer including a cabinet, a drum mounted in the cabinet rotatable by power means for drying laundry, a top cover for covering an upper part of the cabinet, and a rear cover having a front panel mounted in a rear part of the top cover and having a seat identical with the seat of the washing machine and a back panel configured to allow fitting various accessories to be fitted thereto and formed to be fitted to the seat in the front panel, wherein the rear covers of the washing machine and dryer form a unified particular outer appearance on the whole, and are exchangeable to maintain the outer appearance. 38. The washing system as claimed in claim 37, wherein the particular outer appearance is formed by the front panels of the washing machine and the dryer. 39. The washing system as claimed in claim 3S, wherein the particular outer appearance is formed by upper part outlines of the front panels of the washing machine and the dryer. 40. The washing system as claimed in claim 2, wherein the front panels of the washing machine and the dryer are symmetric. 41. The washing system as claimed in claim 37, wherein the front panels include control panels each enabling a user to operate the washing machine or the dryer. 42. The washing system as claimed in claim 41, wherein the control panel includes various buttons for giving operational orders and a display window for displaying an operation state. 43. The washing system as claimed in claim 41, wherein the control panel is unified with the front panel, or detachable from the front panel. 44. The washing system as claimed in claim 43, wherein the windows and buttons have identical positions in the control panels of the washing machine and the dryer. 45. The washing system as claimed in claim 37, wherein the seats are formed by cutting off rear surfaces of the front panels of the washing machine and the dryer. 46. The washing system as claimed in claim 37, wherein the accessories for the washing machine include a water supply tube and wires. 47. The washing system as claimed in claim 37, wherein the accessories for the dryer include wires. 48. The washing system as claimed in claim 37, wherein the back panel of the dryer is formed of a metal. 49. The washing system as claimed in claim 37, wherein the back panel is unified with the top cover. |
<SOH> BACKGROUND ART <EOH>As known, since the washing machine and the dryer provide function supplementary to each other, the washing machine and the dryer are installed even in parallel when required. According to this, a washing system having independent washing machine and dryer combined as one set therein is put into practical use, recently. The washing system has the washing machine and the dryer coupled in view of functions, though independent from each other in view of structure. Moreover, for giving a sense of one system to a user, the washing system has a unified design on the whole. Depending on specification, the washing system may be provided with a control panel, and a rear cover assembly projected from rear of the washing system. Accordingly, in the washing system, particularly, the rear cover assemblies on the washing machine and dryer respectively are designed to have one specific appearance. In the meantime, an air discharge structure for the dryer, and water supply/drain structures for the washing machine may vary with a structure of a house. Therefore, it is required that the washing machine and the dryer in the washing system are installed in the vicinity of the water supply/drain structures and the air discharge structure. However, even if the washing system is installed suitable to the house structure, the washing system may not be harmonious in view of the outer appearance. For an example, in the washing system, the dryer may be disposed on a right side of the washing machine, and under this arrangement, the washing system may be designed to have a particular outer appearance on the whole. However, if it is required that the dryer is disposed on a left side of the washing machine suitable to a structure of a house, arrangement of the washing machine and the dryer may not be harmonious. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>The accompanying drawings, which are included to provide a further understanding of the invention, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention: In the drawings: FIG. 1 illustrates a perspective view of a washing system in accordance with a preferred embodiment of the present invention; FIG. 2 illustrates a back side perspective view of a washing system of the present invention showing a rear cover assembly in detail; and FIGS. 3 A˜ 3 D illustrate back side perspective views each showing the steps of a process for interchanging the rear cover assemblies in the washing system of the present invention. detailed-description description="Detailed Description" end="lead"? |
Equipment for producing high-pressure saturated steam |
This invention relates to an equipment for producing high-pressure saturated steam. The equipment includes a water tank, a pump, a check valve, an atomizing nozzle, a heat chamber and a steam outlet. The pump is connected between water tank and the check valve. The check valve is connected with the heat chamber via the atomizing nozzle. The heat chamber having a steam outlet is hollow into which the atomizing nozzle extends. The hollow chamber is divided into many small chambers which are connected with each other successively. The equipment can produce high temperature steam rapidly and save energy. |
1. Device for generating high-pressure saturated steam, comprising water tank (1), water pump (2), one-way valve (3), atomising nozzle (4), heating chamber (5) and steam outlet (6), in which the water pump (2) links the water tank (1) and one-way valve (3), which connects to atomising nozzle (4), atomising nozzle (4) is connected to heating chamber (5) which has a steam outlet (6) on one side, characterised in that the heating chamber (5) is hollow, installed in which are heating plates (8) that subdivide the chamber into multiple interconnected smaller heating cavities, the atomising nozzle (4) is connected to the first heating cavity (1) in the hollow chamber (5), whilst the last heating cavity in the hollow chamber (5) is connected to steam outlet (6). 2. Device for generating high-pressure saturated steam according to claim 1, characterised in that the hollow chamber (5) is covered externally with a thermal insulating layer (7). 3. Device for generating high-pressure saturated steam according to claim 1, characterised in that the said chamber is a spherical, hollow chamber. 4. Device for generating high-pressure saturated steam according to claim 1, characterised in that the heating plate (8) has a circular main body, in which a heating plate positioning hole (11) is provided to retain the heating bar. |
Recombinant narbonolide polyketide synthase |
Recombinant DNA compounds that encode all or a portion of the narbonolide polyketide synthase are used to express recombinant polyketide synthase genes in host cells for the production of narbonolide, narbonolide derivatives, and polyketides that are useful as antibiotics and as intermediates in the synthesis of compounds with pharmaceutical value. |
1. An isolated recombinant DNA compound that comprises a coding sequence for a domain of a narbonolide PKS. 2. The isolated recombinant DNA compound of claim 1, wherein said domain is selected from the group consisting of a thioesterase domain, a KSQ domain, an AT domain, a KS domain, an ACP domain, a KR domain, a DH domain, and an ER domain. 3. The isolated recombinant DNA compound of claim 2 that comprises the coding sequence for a loading module, thioesterase domain, and all six extender modules of the narbonolide PKS. 4. An isolated recombinant DNA compound that comprises a coding sequence for a desosamine biosynthetic gene or a desosaminyl transferase gene or a beta-glucosidase gene of Streptomyces venezuelae. 5. An isolated recombinant DNA compound that comprises a coding sequence for a picK hydroxylase gene of Streptomyces venezuelae. 6. An isolated DNA compound of any of claim 1 that further comprises a promoter operably linked to said coding sequence. 7. The isolated recombinant DNA compound of claim 6, wherein said promoter is a promoter derived from a cell other than a Streptomyces venezuelae cell. 8. The isolated recombinant DNA compound of claim 7 that is a recombinant DNA expression vector. 9. The recombinant DNA expression vector of claim 8 that expresses a PKS in Streptomyces host cells. 10. The recombinant DNA expression vector of claim 9 that encodes a hybrid PKS comprising at least a portion of a narbonolide PKS gene and at least a portion of a second PKS gene for a macrolide aglycone other than narbonolide. 11. The recombinant DNA compound of claim 10, wherein said second PKS gene is a DEBS gene. 12. The recombinant DNA compound of claim 11, wherein said hybrid PKS is composed of a loading module and extender modules 1 through 6 of DEBS excluding a KR domain of extender module 6 of DEBS and an ACP of extender module 6 and a thioesterase domain of the narbonolide PKS. 13. A recombinant host cell, which in its untransformed state does not produce 10-deoxymethynolide or narbonolide, that comprises a recombinant DNA expression vector of claim 9 that encodes a narbonolide PKS and said cell produces 10-deoxymethynolide or narbonolide. 14. The recombinant host cell of claim 13 that further comprises a picB gene. 15. The recombinant host cell of claim 13 that further comprises desosamine biosynthetic genes and a gene for desosaminyl transferase and produces YC17 or narbomycin. 16. The recombinant host cell of claim 15 that further comprises a picK gene and produces methymycin, neomethymycin, or picromycin. 17. The recombinant host cell of any of claim 16 that is Streptomyces coelicolor or Streptomyces lividans. 18. A recombinant host cell other than a Streptomyces venezuelae cell that expresses a picK hydroxylase gene of S. venezuelae encoded by the DNA compound of claim 5. 19. A recombinant host cell other than a Streptomyces venezuelae host cell that expresses a desosamine biosynthetic gene or desosaminyl transferase gene of S. venezuelae encoded by the DNA compound of claim 4. 20. A method for increasing the yield of a desosaminylated polyketide in a cell, which method comprises transforming the cell with a recombinant expression vector that encodes a functional beta-glucosidase gene. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Polyketides represent a large family of diverse compounds synthesized from 2-carbon units through a series of condensations and subsequent modifications. Polyketides occur in many types of organisms, including fungi and mycelial bacteria, in particular, the actinomycetes. There are a wide variety of polyketide structures, and the class of polyketides encompasses numerous compounds with diverse activities. Tetracycline, erythromycin, FK506, FK520, narbomycin, picromycin, rapamycin, spinocyn, and tylosin, are examples of such compounds. Given the difficulty in producing polyketide compounds by traditional chemical methodology, and the typically low production of polyketides in wild-type cells, there has been considerable interest in finding improved or alternate means to produce polyketide compounds. See PCT publication Nos. WO 93/13663; WO 95/08548; WO 96/40968; 97/02358; and 98/27203; U.S. Pat. Nos. 4,874,748; 5,063,155; 5,098,837; 5,149,639; 5,672,491; and 5,712,146; Fu et al., 1994, Biochemistry 33: 9321-9326; McDaniel et al., 1993, Science 262: 1546-1550; and Rohr, 1995, Angew. Chem. Int. Ed. Engl. 34(8): 881-888, each of which is incorporated herein by reference. Polyketides are synthesized in nature by polyketide synthase (PKS) enzymes. These enzymes, which are complexes of multiple large proteins, are similar to the synthases that catalyze condensation of 2-carbon units in the biosynthesis of fatty acids. PKS enzymes are encoded by PKS genes that usually consist of three or more open reading frames (ORFs). Each ORF typically comprises two or more “modules” of ketosynthase activity, each module of which consists of at least two (if a loading module) and more typically three or more enzymatic activities or “domains.” Two major types of PKS enzymes are known; these differ in their composition and mode of synthesis. These two major types of PKS enzymes are commonly referred to as Type I or “modular” and Type II “iterative” PKS enzymes. Modular PKSs are responsible for producing a large number of 12, 14, and 16-membered macrolide antibiotics including methymycin, erythromycin, narbomycin, picromycin, and tylosin. These large multifunctional enzymes (>300,000 kDa) catalyze the biosynthesis of polyketide macrolactones through multistep pathways involving decarboxylative condensations between acyl thioesters followed by cycles of varying β-carbon processing activities (see O'Hagan, D. The polyketide metabolites ; E. Horwood: New York, 1991, incorporated herein by reference). During the past half decade, the study of modular PKS function and specificity has been greatly facilitated by the plasmid-based Streptomyces coelicolor expression system developed with the 6-deoxyerythronolide B (6-dEB) synthase (DEBS) genes (see Kao et al., 1994, Science, 265: 509-512, McDaniel et al., 1993, Science 262: 1546-1557, and U.S. Pat. Nos. 5,672,491 and 5,712,146, each of which is incorporated herein by reference). The advantages to this plasmid-based genetic system for DEBS were that it overcame the tedious and limited techniques for manipulating the natural DEBS host organism, Saccharopolyspora erythaea , allowed more facile construction of recombinant PKSs, and reduced the complexity of PKS analysis by providing a “clean” host background. This system also expedited construction of the first combinatorial modular polyketide library in Streptomyces (see PCT publication No. WO 98/49315, incorporated herein by reference). The ability to control aspects of polyketide biosynthesis, such as monomer selection and degree of β-carbon processing, by genetic manipulation of PKSs has stimulated great interest in the combinatorial engineering of novel antibiotics (see Hutchinson, 1998, Curr. Opin. Microbiol. 1: 319-329; Carreras and Santi, 1998, Curr. Opin. Biotech. 9: 403-411; and U.S. Pat. Nos. 5,712,146 and 5,672,491, each of which is incorporated herein by reference). This interest has resulted in the cloning, analysis, and manipulation by recombinant DNA technology of genes that encode PKS enzymes. The resulting technology allows one to manipulate a known PKS gene cluster either to produce the polyketide synthesized by that PKS at higher levels than occur in nature or in hosts that otherwise do not produce the polyketide. The technology also allows one to produce molecules that are structurally related to, but distinct from, the polyketides produced from known PKS gene clusters. The present invention provides methods and reagents relating to the PKS gene cluster for the polyketide antibiotics known as narbomycin and picromycin. Narbomycin is produced in Streptomyces narbonensis , and both narbomycin and picromycin are produced in S. venezuelae . These species are unique among macrolide producing organisms in that they produce, in addition to the 14-membered macrolides narbomycin and picromycin (picromycin is shown in FIG. 1 , compound 1), the 12-membered macrolides neomethymycin and methymycin (methymycin is shown in FIG. 1 , compound 2). Based on the structural similarities between picromycin and methymycin, it was speculated that methymycin would result from premature cyclization of a hexaketide intermediate in the picromycin pathway. Glycosylation of the C5 hydroxyl group of the polyketide precursor, narbonolide, is achieved through an endogenous desosaminyl transferase to produce narbomycin. In Streptomyces venezuelae , narbomycin is then converted to picromycin by the endogenously produced narbomycin hydroxylase. Thus, as in the case of other macrolide antibiotics, the macrolide product of the narbonolide PKS is further modified by hydroxylation and glycosylation. Picromycin ( FIG. 1 , compound 1) is of particular interest because of its close structural relationship to ketolide compounds (e.g. HMR 3004, FIG. 1 , compound 3). The ketolides are a new class of semi-synthetic macrolides with activity against pathogens resistant to erythromycin (see Agouridas et al., 1998, J. Med. Chem. 41: 4080-4100, incorporated herein by reference). Thus, genetic systems that allow rapid engineering of the narbonolide PKS would be valuable for creating novel ketolide analogs for pharmaceutical applications. Furthermore, the production of picromycin as well as novel compounds with useful activity could be accomplished if the heterologous expression of the narbonolide PKS in Streptomyces lividans and other host cells were possible. The present invention meets these and other needs. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides recombinant methods and materials for expressing PKSs derived in whole and in part from the narbonolide PKS and other genes involved in narbomycin and picromycin biosynthesis in recombinant host cells. The invention also provides the polyketides derived from the narbonolide PKS. The invention provides the complete PKS gene cluster that ultimately results, in Streptomyces venezuelae , in the production of picromycin. The ketolide product of this PKS is narbonolide. Narbonolide is glycosylated to obtain narbomycin and then hydroxylated at C12 to obtain picromycin. The enzymes responsible for the glycosylation and hydroxylation are also provided in recombinant form by the invention. Thus, in one embodiment, the invention is directed to recombinant materials that contain nucleotide sequences encoding at least one domain, module, or protein encoded by a narbonolide PKS gene. The invention also provides recombinant materials useful for conversion of ketolides to antibiotics. These materials include recombinant DNA compounds that encode the C12 hydroxylase (the picK gene), the desosamine biosynthesis and desosaminyl transferase enzymes, and the beta-glucosidase enzyme involved in picromycin biosynthesis in S. venezuelae and the recombinant proteins that can be produced from these nucleic acids in the recombinant host cells of the invention. In one embodiment, the invention provides a recombinant expression vector that comprises a heterologous promoter positioned to drive expression of the narbonolide PKS. In a preferred embodiment, the promoter is derived from a PKS gene. In a related embodiment, the invention provides recombinant host cells comprising the vector that produces narbonolide. In a preferred embodiment, the host cell is Streptomyces lividans or S. coelicolor. In another embodiment, the invention provides a recombinant expression vector that comprises the desosamine biosynthetic genes as well as the desosaminyl transferase gene. In a related embodiment, the invention provides recombinant host cells comprising the vector that produces the desosamine biosynthetic gene products and desosaminyl transferase gene product. In a preferred embodiment, the host cell is Streptomyces lividans or S. coelicolor. In another embodiment, the invention provides a method for desosaminylating polyketide compounds in recombinant host cells, which method comprises expressing the PKS for the polyketide and the desosaminyl transferase and desosamine biosynthetic genes in a host cell. In a preferred embodiment, the host cell expresses a beta-glucosidase gene as well. This preferred method is especially advantageous when producing desosaminylated polyketides in Streptomyces host cells, because such host cells typically glucosylate desosamine residues of polyketides, which can decrease desired activity, such as antibiotic activity. By coexpression of beta-glucosidase, the glucose residue is removed from the polyketide. In another embodiment, the invention provides the picK hydroxylase gene in recombinant form and methods for hydroxylating polyketides with the recombinant gene product. The invention also provides polyketides thus produced and the antibiotics or other useful compounds derived therefrom. In another embodiment, the invention provides a recombinant expression vector that comprises a promoter positioned to drive expression of a hybrid PKS comprising all or part of the narbonolide PKS and at least a part of a second PKS. In a related embodiment, the invention provides recombinant host cells comprising the vector that produces the hybrid PKS and its corresponding polyketide. In a preferred embodiment, the host cell is Streptomyces lividans or S. coelicolor. In a related embodiment, the invention provides recombinant materials for the production of libraries of polyketides wherein the polyketide members of the library are synthesized by hybrid PKS enzymes of the invention. The resulting polyketides can be further modified to convert them to other useful compounds, such as antibiotics, typically through hydroxylation and/or glycosylation. Modified macrolides provided by the invention that are useful intermediates in the preparation of antibiotics are of particular benefit. In another related embodiment, the invention provides a method to prepare a nucleic acid that encodes a modified PKS, which method comprises using the narbonolide PKS encoding sequence as a scaffold and modifying the portions of the nucleotide sequence that encode enzymatic activities, either by mutagenesis, inactivation, insertion, or replacement. The thus modified narbonolide PKS encoding nucleotide sequence can then be expressed in a suitable host cell and the cell employed to produce a polyketide different from that produced by the narbonolide PKS. In addition, portions of the narbonolide PKS coding sequence can be inserted into other PKS coding sequences to modify the products thereof. The narbonolide PKS can itself be manipulated, for example, by fusing two or more of its open reading frames, particularly those for extender modules 5 and 6, to make more efficient the production of 14-membered as opposed to 12-membered macrolides. In another related embodiment, the invention is directed to a multiplicity of cell colonies, constituting a library of colonies, wherein each colony of the library contains an expression vector for the production of a modular PKS derived in whole or in part from the narbonolide PKS. Thus, at least a portion of the modular PKS is identical to that found in the PKS that produces narbonolide and is identifiable as such. The derived portion can be prepared synthetically or directly from DNA derived from organisms that produce narbonolide. In addition, the invention provides methods to screen the resulting polyketide and antibiotic libraries. The invention also provides novel polyketides and antibiotics or other useful compounds derived therefrom. The compounds of the invention can be used in the manufacture of another compound. In a preferred embodiment, the antibiotic compounds of the invention are formulated in a mixture or solution for administration to an animal or human. These and other embodiments of the invention are described in more detail in the following description, the examples, and claims set forth below. |
Method of manufacturing metallic composite material |
Disclosed is a method of manufacturing a metallic composite material for use as building material, the metallic composite material including an aluminium core sheet and a titanium clad layer on at least one side of the core sheet. The aluminium core sheet and titanium clad layer are bonded to one another by roll-bonding wherein only the aluminium core sheet prior to roll bonding is preheated to a temperature in the range of 50 to 200° C. The use of such metallic composite material and to a metallic composite material as such are also disclosed. |
1. A method of manufacturing a metallic composite material for use as building material, said metallic composite material comprising an aluminium core sheet and a titanium cladding layer on at least one side of the core sheet, wherein the aluminium core sheet and titanium cladding layer are bonded to one another by roll-bonding wherein only the aluminium core sheet prior to roll bonding is preheated to a temperature in the range of 50 to 200° C. 2. A method according to claim 1, wherein the aluminium core sheet and titanium cladding layer are bonded to one another by roll-bonding wherein only the aluminium core sheet prior to roll bonding is preheated to a temperature in the range of 110 to 200° C. 3. A method according to claim 1, wherein the roll-bonding is carried out with a total rolling degree of not more than 50%. 4. A method according to claim 3, wherein the roll-bonding is carried out with a total rolling degree of not more than 45%. 5. A method according to claim 3, wherein the roll-bonding is carried out with a total rolling degree of not more than 40%. 6. A method according to claim 1, wherein the roll-bonding is carried out with a total rolling degree of at least 25%. 7. A method according to claim 6, wherein the roll-bonding is carried out with a total rolling degree of at least 30%. 8. A method according to claim 1, wherein the roll-bonding is carried out in one single rolling step. 9. A method according to claim 1, wherein the method includes pre-treatment of the surface of the titanium cladding layer facing the aluminium core sheet said pre-treatment comprises the step of brushing of said surface before the bonding step. 10. A method according to claim 9 wherein the pre-treatment is carried out in a substantially dry atmosphere. 11. A method according to claim 9 wherein the pre-treatment is carried out in an inert gas atmosphere. 12. A method according to claim 1, wherein the aluminium core sheet has a composition within a range selected from of AA1000, AA6000, or AA3000-series aluminium alloys. 13. A method according to claim 1, wherein the aluminium core sheet is made of an AA3004-series aluminium alloy. 14. A method according to claim 1, wherein the titanium cladding layer has a composition, in weight percent, comprising: Fe 0.35 max. O 0.35 max. N 0.05 max. C 0.06 max. H 0.015% max. impurities each 0.1% max., total 0.4% max., balance titanium. 15. A method according to claim 14, wherein the titanium cladding layer has a composition, in weight percent, comprising Fe of 0.15% max. 16. A method according to claim 14, wherein the titanium cladding layer has a composition, in weight percent, comprising O of 0.12% max. 17. A method according to claim 1, wherein the titanium cladding layer has a composition, in weight percent, consisting of: Fe 0.35 max. O 0.35 max. N 0.05 max. C 0.06 max. H 0.015% max. impurities each 0.1% max., total 0.4% max., balance titanium. 18. A method according to claim 1, wherein said aluminium core sheet has a thickness after roll-bonding in the range of 0.7 to 1.5 mm. 19. A method according to claim 1, wherein said aluminium core sheet has a thickness after roll-bonding in the range of 0.9 to 1.25 mm. 20. A method according to claim 1, wherein one or both of said titanium cladding layer or layers have each a thickness after roll-bonding in the range of 0.05 to 0.4 mm. 21. A method according to claim 1, wherein one or both of said titanium cladding layer or layers have each a thickness after roll-bonding in the range of 0.05 to 0.3 mm. 22. A method according to claim 1, wherein following the roll-bonding of the sheet products into a composite material, the composite material is subjected to a final annealing by holding the composite material for 2 to 16 hours at a temperature in a range of 350 to 550° C. 23. A method according to claim 1, wherein following the roll-bonding of the sheet products into a composite material, the composite material is subjected to a final annealing by holding the composite material for 2 to 16 hours at a temperature in a range of 400 to 540° C. 24. Metallic composition in sheet form, comprising a sheet of aluminium alloy and a titanium cladding layer applied on one side of the aluminium alloy sheet, wherein said titanium cladding layer is applied on the core sheet by means of roll-bonding and wherein only the aluminium core sheet prior to roll bonding has been preheated to a temperature in a range of 50 to 200° C., the thickness of the aluminium core sheet is in the range of 0.7 to 1.5 mm and the thickness of the titanium cladding layer is in the range of 0.05 to 0.3 mm, the aluminium sheet has a composition within the ranges of AA3000-series aluminium alloys, and the titanium cladding layer has a composition, in weight percent, comprising: Fe 0.35 max. O 0.35max. N 0.05 max. C 0.06 max. H 0.015% max. impurities each 0.1% max., total 0.4% max., balance titanium. 25. Metallic composite sheet according to claim 24, wherein the metallic composite sheet is a building sheet and the aluminium alloy is made of the AA3004-series aluminium alloy. 26. Metallic composite sheet according to claim 24, consisting of the sheet of aluminium alloy and the titanium cladding layer applied on one side of the aluminium alloy sheet. |
Under reamer |
An under reamer for expanding a borehole through an earthen formation is taught. The under reamer includes: a mandrel including an end for connection into a drill string and an opposite end and a housing including an inner bore, telescopically disposed over the mandrel and axially moveable relative to the mandrel but rotationally moveable with the mandrel. A plurality of under reamer arms are carried on the housing, the under reamer arms are formed as blocks including cutter-supporting portions in which poly-crystalline diamond compact cutters are mounted. The under reamer arms are moveable by driving the housing axially over the mandrel between a retracted position extending into the bore of the housing and an expanded position wherein the under reamers arms are pivoted out of the housing inner bore and supported therebehind by the mandrel such that the cutter-supporting portions are exposed for use to enlarge a borehole. The under reamer can include one or more lock assemblies for releasably locking the mandrel and housing against relative axial movement. The under reamer can also or alternately include a restriction nozzle to facilitate hydraulic operation thereof. |
1. An under reamer for expanding a borehole through an earthen formation, the under reamer comprising: a mandrel including an end for connection into a drill string and an opposite end; a housing including an inner bore, telescopically disposed over the mandrel and axially moveable relative to the mandrel, the housing being rotationally moveable with the mandrel; and a plurality of under reamer arms carried on the housing, the under reamer arms formed as blocks including cutter-supporting portions in which poly-crystalline diamond compact cutters are mounted, the under reamer arms being moveable by driving the housing axially over the mandrel between a retracted position extending into the bore the housing and an expanded position wherein the under reamer arms are pivoted out of the housing inner bore and supported by the mandrel such that the cutter-supporting portions are exposed for use to enlarge a borehole. 2. The under reamer of claim 1 further comprising a hydraulic pressure chamber between the housing and the mandrel for driving the housing axially relative to the mandrel. 3. The under reamer of claim 1 further comprising slots in the housing extending between the housing outer surface and the housing inner bore and the under reamer arms being pivotally mounted therein. 4. The under reamer of claim 3 wherein each slot includes side, top and bottom surfaces that extend between the housing outer surface and the housing inner bore and the under reamer arms each include a outer facing surface and a rear surface and top, bottom and side surfaces extending between the outer facing surface and the rear surface and wherein the cutter supporting portions of the arm is a protrusion on the outer facing surface of the arm. 5. The under reamer of claim 4 wherein in the expanded position, at least a portion of the arm top, bottom and side surfaces remain in the slot with the cutter supporting portions extending outwardly beyond the housing outer surface. 6. The under reamer of claim 1 wherein the under reamer arms each include a rear surface, and a portion of the rear surfaces being wedge-shaped to permit the under reamer arms to fit together in the housing inner bore about the inner bore center axis. 7. The under reamer of claim 6 wherein the mandrel includes a contour on its surface which supports the under reamer arms in the expanded position and the under reamer arms each include another portion of their rear surface that is curved to substantially conform to the contour of the mandrel surface. 8. The under reamer of claim 1, further comprising a releasable lock between at least one under reamer arm and its slot to releasably lock the arm in the slot when in the retracted position. 9. The under reamer of claim 1, further comprising an operational lock assembly operable to releasably lock the mandrel relative to the housing in an axial position corresponding to the expanded position. 10. The under reamer of claim 1, further comprising a tripping lock assembly operable to releasably lock the mandrel relative to the housing in an axial position corresponding to the retracted position. 11. The under reamer of claim 10, wherein the tripping lock assembly is operable to unlock by application of a selected fluid pressure to the mandrel. 12. An under reamer for expanding a borehole through an earthen formation, the under reamer comprising: a mandrel including an end for connection into a drill string and an opposite end; a housing telescopically disposed over the mandrel and axially moveable relative to the mandrel, the housing being rotationally moveable with the mandrel; a plurality of under reamer arms carried on the housing, the under reamer arms each including a cutter-supporting portion; and a slot for each under reamer arm, the slots extending from the outer surface of the housing to the housing inner bore; the under reamer arms each being pivotally moveable within their slots between a stored position in the slot and extending into the inner bore and an expanded position wherein the cutter-supporting portions extend beyond the outer surface of the housing for use to enlarge a borehole. 13. The under reamer of claim 12 wherein the slots include sides and the under reamer arms include sides and the sides of the slots are formed to substantially conform to the sides of the arms. 14. The under reamer of claim 12 wherein the slots each include an upper end and the under reamer arms each include an upper surface and the upper ends of the slots are formed to limit the pivotal movement of the arms into their extended position by abutment of the arms upper surfaces against the upper ends of the slots. 15. The under reamer of claim 14, wherein the upper ends of the slots substantially conform to the shape of the upper surfaces of the under reamer arms. 16. The under reamer of claim 12 wherein the mandrel includes an outer surface and the under reamer arms each include a rear surface and the rear surfaces of the under reamer arms are shaped to substantially conform to the outer surface of the mandrel. 17. The under reamer of claim 16 wherein the under reamer arms each include a wedge shaped portion on their rear surfaces to permit an interfit between the arms in the stored position. 18. The under reamer of claim 12 further comprising a releasable lock between at least one under reamer arm and the slot in which it is mounted to releasably lock the under reamer arm in the stored position within the slot. 19. An under reamer for expanding a borehole through an earthen formation, the under reamer comprising: a mandrel including an end for connection into a drill string and an opposite end; a housing telescopically disposed over the mandrel and axially moveable relative to the mandrel, the housing being rotationally moveable with the mandrel; a plurality of under reamer arms carried on the housing, the under reamer arms including cutter-supporting portions and being moveable by driving the housing axially over the mandrel between a stored position against the housing and an expanded position wherein the cutter-supporting portions are exposed for use to enlarge a borehole; and a lock for releasably locking the housing in relative axial position on the mandrel. 20. The under reamer of claim 19 wherein the lock releasably locks the housing in a position on the mandrel to maintain the under reamer arms in the stored position. 21. The under reamer of claim 19 wherein the lock releasably locks the housing in an operational position on the mandrel to maintain the under reamer arms in the expanded position. 22. An under reamer for expanding a borehole through an earthen formation, the under reamer comprising: a mandrel including an uphole end for connection into a drill string and an opposite end and an inner bore extending between the uphole end and the opposite end; a housing including an inner bore, telescopically disposed over the mandrel and axially moveable relative to the mandrel, the housing being rotationally moveable with the mandrel; a plurality of under reamer arms carried on the housing, the under reamer arms each including a cutter-supporting portion in which cutters are mounted, the under reamer arms being moveable by driving the housing axially over the mandrel between a stored position extending into the bore the housing and an expanded position wherein the under reamers arms are pivoted out of the housing inner bore and supported by the mandrel such that the cutter-supporting portions are exposed for use to enlarge a borehole; a fluid pressure chamber positioned between the housing and the mandrel and formed to accept pressurized fluid therein to drive the axial movement of the housing relative to the mandrel, a port from the mandrel inner bore to the pressure chamber to permit flow of pressurized fluid therethrough; and a restriction nozzle in the mandrel inner bore between the port and the opposite end of the mandrel to increase fluid pressure thereabove. 23. The under reamer of claim 22, wherein the housing inner bore is formed as a fluid diffuser. |
<SOH> BACKGROUND OF THE INVENTION <EOH>When drilling a borehole through an earthen formation a pilot hole is drilled by a pilot bit and the hole can be enlarged by an under reamer. Under reamers have arms with cutters thereon that cut into the formation to enlarge the borehole to its intended gauge. Under reamers are useful in casing drilling, wherein the pilot bit must be of a size to pass through the bore of the casing and is, therefore, not sized to drill a borehole of a gauge that the casing can pass therethrough. Therefore, the pilot bit drills the pilot hole into the formation and under reamers enlarge the hole behind the pilot bit to a gauge greater than the casing outer diameter to permit advancement of the casing into the borehole. Under reamers are also useful when extending a borehole below installed casing. In such embodiments, the under reamer arms are collapsible to permit the under reamer to be moved through the bore of the casing and are expandable downhole to permit drilling of a borehole to a gauge greater than the outer diameter of the casing. |
<SOH> SUMMARY OF THE INVENTION <EOH>An under reamer has been invented, which facilitates tripping through the casing inner bore and facilitates deployment of the under reamer arms down hole. In accordance with one broad aspect of the present invention there is provided an under reamer for expanding a borehole through an earthen formation, the under reamer comprising: a mandrel including an end for connection into a drill string and an opposite end; a housing including an inner bore, telescopically disposed over the mandrel and axially moveable relative to the mandrel, the housing being rotationally moveable with the mandrel; and a plurality of under reamer arms carried on the housing, the under reamer arms formed as blocks including cutter-supporting portions in which poly-crystalline diamond compact cutters are mounted, the under reamer arms being moveable by driving the housing axially over the mandrel between a stored position extending into the inner bore of the housing and an expanded position wherein the under reamer arms are pivoted out of the housing inner bore and supported by the mandrel such that the cutter-supporting portions are exposed for use to enlarge a borehole. The axial movement of the housing relative to the mandrel can be driven by weight on bit or by fluid pressure inside the drill string. In one embodiment, the under reamer includes a hydraulic pressure chamber between the housing and the mandrel for driving the housing axially relative to the mandrel. The under reamer can include slots in the housing extending between the housing outer surface and the housing inner bore wherein the under reamer arms are pivotally mounted. The slots permit the rear surfaces of the under reamer arms to be open for driving contact with the mandrel. A portion of the rear surfaces can be wedge-shaped to permit the under reamer arms to fit together in the housing inner bore about the inner bore center axis. In addition or alternately, the under reamer rear surfaces can be formed to substantially conform to the outer surface contour of the portion of the mandrel which is positioned behind the arms when they are in the expanded position. This enhances the support provided by the mandrel for the arms, when the arms are in the expanded position. In accordance with another aspect of the present invention, there is provided an under reamer for enlarging a borehole through an earthen formation, the under reamer comprising: a mandrel including an end for connection into a drill string and an opposite end; a housing telescopically disposed over the mandrel and axially moveable relative to the mandrel, the housing being rotationally moveable with the mandrel; a plurality of under reamer arms carried on the housing, the under reamer arms each including a cutter-supporting portion; and a slot for each under reamer arm, the slots extending from the outer surface of the housing to the housing inner bore; the under reamer arms each being pivotally moveable within their slots between a stored position in the slot and extending into the inner bore and an expanded position wherein the cutter-supporting portions extend beyond the outer surface of the housing for use to enlarge a borehole. The sides of the slots can be formed to substantially conform to the shape of the sides of the arms, so that the arms are supported by the slots. Preferably, the arms are formed such that, in the expanded position, they remain at least in part in the slot with their cutter supporting portions extending from the slot. The upper ends of the slots can be formed to limit the pivotal movement of the arms into their extended position by abutment of the arm upper surfaces against the upper ends of the slots. The upper ends of the slots can substantially conform to the shape of the upper surfaces of the under reamer arms, to enhance transfer of shock to the housing. The under reamer can include a releasable lock between each under reamer arm and the slot in which it is mounted to releasably lock the under reamer arm in the stored position within the slot. In accordance with another aspect of the present invention, there is provided an under reamer for enlarging a borehole through an earthen formation, the under reamer comprising: a mandrel including an end for connection into a drill string and an opposite end; a housing telescopically disposed over the mandrel and axially moveable relative to the mandrel, the housing being rotationally moveable with the mandrel; a plurality of under reamer arms carried on the housing, the under reamer arms including cutter-supporting portions and being moveable by driving the housing axially over the mandrel between a stored position against the housing and an expanded position wherein the cutter-supporting portions are exposed for use to enlarge a borehole; and a lock for releasably locking the housing in relative axial position on the mandrel. The lock can releasably lock the housing in a position on the mandrel to maintain the under reamer arms in the stored position or, alternately, the lock can releasably lock the housing in an operational position on the mandrel to maintain the under reamer arms in the expanded position. In one embodiment, the operational lock is actuated to unlock by application of fluid pressure to the under reamer, the fluid pressure being selected to be greater than that present during tripping of the under reamer. In accordance with another aspect of the present invention, there is provided an under reamer for expanding a borehole through an earthen formation, the under reamer comprising: a mandrel including an uphole end for connection into a drill string and an opposite end and an inner bore extending between the uphole end and the opposite end; a housing including an inner bore, telescopically disposed over the mandrel and axially moveable relative to the mandrel, the housing being rotationally moveable with the mandrel; a plurality of under reamer arms carried on the housing, the under reamer arms each including a cutter-supporting portion in which cutters are mounted, the under reamer arms being moveable by driving the housing axially over the mandrel between a stored position extending into the inner bore of the housing and an expanded position wherein the under reamers arms are pivoted out of the housing inner bore and supported by the mandrel such that the cutter-supporting portions are exposed for use to enlarge a borehole; a fluid pressure chamber positioned between the housing and the mandrel and formed to accept pressurized fluid therein to drive the axial movement of the housing relative to the mandrel, a port from the mandrel inner bore to the pressure chamber to permit flow of pressurized fluid therethrough; and a restriction nozzle in the mandrel inner bore between the port and the opposite end of the mandrel to increase fluid pressure thereabove. The housing inner bore can formed as a fluid diffuser to restore fluid pressure passing through to the pilot bit. |
Therapeutic methods using herbal compositions |
Compositions derived from traditional Chinese herbal medicines, medicinal plants and extracts thereof, are provided for the prevention and treatment of cancers especially lung cancer, prostate cancer, liver cancer, breast cancer and leukemia. The composition is also useful for treating Helicobacter pylori infection The composition is also useful for treating or preventing a chronic inflammatory condition. The composition is also useful for treating or preventing cardiovascular disease. The composition is also useful for treating or preventing cerebral vascular disease. The compositions are useful as adjuncts to conventional surgery, chemotherapy or radiotherapy treatments in patients with cancer. Preferred compositions of the invention contain the herbal ingredients Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. |
1-50. (canceled) 51. A method of preventing or treating cancer in a patient in need thereof, said method comprising administering an effective amount of a composition comprising a mixture of Sophora tonkinensis, Polygonum bistorta and Prunella vulgaris; wherein the cancer is selected from the group consisting of lung cancer, prostate cancer, bladder cancer, liver cancer, breast cancer and leukemia. 52. The method of claim 51, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris and Dictamnus dasycarpus Turcz. 53. The method of claim 52, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus and Dictamnus dasycarpus Turcz. 54. The method of claim 53, wherein the composition comprises a mixture of the following herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. 55. A method of treating Helicobacter pylori infection in a patient in need thereof, said method comprising administering an effective amount of a composition comprising a mixture of Sophora tonkinensis, Polygonum bistorta and Prunella vulgaris. 56. The method of claim 55, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris and Dictamnus dasycarpus Turcz. 57. The method of claim 56, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus and Dictamnus dasycarpus Turcz. 58. The method of claim 57, wherein the composition comprises a mixture of the following herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. 59. A method of treating or reducing the reoccurrence of cancer in a patient in need, said method comprising administering an effective amount of a composition comprising a mixture of Sophora tonkinensis, Polygonum bistorta and Prunella vulgaris. 60. The method of claim 59, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris and Dictamnus dasycarpus Turcz. 61. The method of claim 60, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus and Dictamnus dasycarpus Turcz. 62. The method of claim 61, wherein the composition comprises a mixture of the following herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. 63. The method of claim 59, wherein said composition is used as an adjunct to convention surgery, chemotherapy or radiation therapy treatments. 64. A method of treating or preventing a chronic inflammatory condition in a patient in need thereof, said method comprising administering an effective amount of a composition comprising a mixture of Sophora tonkinensis, Polygonum bistorta and Prunella vulgaris. 65. The method of claim 64, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris and Dictamnus dasycarpus Turcz. 66. The method of claim 65, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus and Dictamnus dasycarpus Turcz. 67. The method of claim 66, wherein the composition comprises a mixture of the following herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. 68. A method of treating or preventing cardiovascular disease in a patient in need thereof, said method comprising administering an effective amount of a composition comprising a mixture of Sophora tonkinensis, Polygonum bistorta and Prunella vulgaris. 69. The method of claim 68, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris and Dictamnus dasycarpus Turcz. 70. The method of claim 69, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus and Dictamnus dasycarpus Turcz. 71. The method of claim 70, wherein the composition comprises a mixture of the following herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. 72. A method treating or preventing cerebral vascular disease in a patient in need thereof, said method comprising administering an effective amount of a composition comprising a mixture of Sophora tonkinensis, Polygonum bistorta and Prunella vulgaris. 73. The method of claim 72, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris and Dictamnus dasycarpus Turcz. 74. The method of claim 73, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus and Dictamnus dasycarpus Turcz. 75. The method of claim 74, wherein the composition comprises a mixture of the following herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. 76. A method of preventing the occurrence of or treating precancerous cells in a patient in need thereof, said method comprising administering an effective amount of a composition comprising a mixture of Sophora tonkinensis, Polygonum bistorta and Prunella vulgaris. 77. The method of claim 76, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris and Dictamnus dasycarpus Turcz. 78. The method of claim 77, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus and Dictamnus dasycarpus Turcz. 79. The method of claim 78, wherein the composition comprises a mixture of the following herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. 80. The method of claim 76, wherein the composition is used for the prevention or treatment of bronchial dysplasia. 81. The method of claim 80, wherein the composition is used for the prevention or treatment of bronchial dysplasia wherein the method is for the prevention or treatment of chronic obstructive pulmonary disease. 82. A method of treating or preventing atrophic gastritis in a patient in need thereof, said method comprising administering an effective amount of a composition comprising a mixture of Sophora tonkinensis, Polygonum bistorta and Prunella vulgarism. 83. The method of claim 82, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris and Dictamnus dasycarpus Turcz. 84. The method of claim 83, wherein the composition comprises a mixture of the following herbs: Sophora tonkinesis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus and Dictamnus dasycarpus Turcz. 85. The method of claim 84, wherein the composition comprises a mixture of the following herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. 86. A composition consisting essentially of a mixture of at least three different herbs selected from the group consisting of: Herb A, Herb B, Herb C, Herb D and Herb E, wherein Herb A is Sophora tonkinensis (Sophora subprostrata) Herb B is Polygonum bistorta Herb C is Prunella vulgaris Herb D is selected from the group consisting of: Sonchus brachyotus Patrinia scabiosaefolia Fisch. Patrinia villosa Juss. Sonchus arvensis L. Thlaspi arvense L. Portulaca oleracea L. and Pulsatilla chinensis Reg. and Herb E is selected from the group consisting of: Dictamnus dasycarpus Kochia scoparia (L.) Schard. Sophora flavescens Ait. and Heydyotis diffusa (Willd.) Roxb; wherein, when the composition comprises three herbs, they are present in an amount from about 9% to about 57%; when the composition comprises four herbs, they are present in an amount from about 6% to about 43% or when the composition comprises four herbs, the first three are selected from the group consisting of Herb A, Herb B, Herb C and Herb D and are present in an amount from about 7% to about 57% and the fourth is selected from Herb E and is present in an amount from about 3.5% to about 28.5%; and when the composition comprises five herbs they are present in an amount from about 5% to about 35% or the first four herbs are selected from the group consisting of Herb A, Herb B, Herb C and Herb D and are present in an amount from about 6% to about 38% and the fifth herb is selected from Herb E and is present in an amount from about 3% to about 19%. 87. The composition of claim 86 further comprising a sixth herb, Herb F, selected from the group consisting of: Dioscorea bulbifera Panax notoginseng (Burk) F. H. Chen. Bletilla striata (Thunb.) Reichb.f. Nelumbo nucifera Gaertn. Polygonum bistorta L. Cephalanoplos segetum (Boge) Kitam. Cirsium japonicum DC. Sophora japonica L. Typha angustifolia L. and Rubia cordifolia L.; wherein the first five herbs are selected from the group consisting of Herb A, Herb B, Herb C, Herb D and Herb E wherein the herbs are present in an amount from about 5% to about 33% and the sixth herb is selected from Herb F and is present in an amount from about 1.0% to about 9.5% or the first four herbs are selected from the group consisting of Herb A, Herb B, Herb C or Herb D and is present in an amount from about 5% to about 38% and the fifth is selected from Herb E and is present in an amount from about 2.5% to about 19% and the sixth herb is selected from Herb F and is present in an amount from about 1% to about 9.5%. 88. The composition of claim 87, wherein Herb F is present in an amount of up to about 3.0% 89. The composition of claim 88, wherein Herb F is present in an amount of up to about 1.4%. 90. The composition of claim 89, wherein Herb F is present in an amount of about 1.4%. |
<SOH> BACKGROUND OF THE INVENTION <EOH>For the past twenty-five years there has been significant progress in the field of cancer research; however, in spite of these positive results, the mortality rate for the most common cancers still remains high. Indeed, the goal of the National Cancer Institute of a fifty percent reduction in overall cancer mortality by the year 2000 has not been met. The term “cancer” is a general one referring to more than 100 forms of the disease which may manifest itself in almost every tissue type of the body. Of the myriad forms of cancer, lung cancer is the most common cause of death worldwide, followed by stomach cancer. Other common forms of cancer include cancers of the colon, rectum, breast, prostate, mouth and esophagus. Lung cancer imposes an enormous burden on health care. The World Health Report 2000 estimates that lung cancer has resulted in 860,000 deaths among men and 333,000 deaths among women per year, and it is the leading cause of cancer deaths worldwide. In the United States and Canada, more people are dying from lung cancer than from breast cancer, colorectal cancer and prostate cancer combined. In addition, the incidence of lung cancer in women is rising at an average annual rate of 7% which is the most rapid rate of increase for any cancer. The most dominant cause of lung cancer is tobacco use, but occupational and environmental exposure to various other carcinogenic substances can also influence disease development. In long-term smokers, the risk of lung cancer never returns to the “baseline” level of a never-smoker, even years after smoking cessation. With a large reservoir (100 million in the United States and Canada alone) of current and former smokers, who are at risk, lung cancer will continue to be a major health problem for at least several more decades even if current efforts to curb tobacco smoking were successful. The overall five-year survival rate of lung cancer is less than 15%. Despite advances in modern medicine, the survival rate has not improved substantially over the last two decades. A different approach is therefore needed to control lung cancer. Prostate cancer is the most commonly diagnosed male malignancy in the United States and the second leading cause of cancer death. It is estimated that in the year 2000, there will be 180,400 new cases and 31,900 deaths caused by prostate cancer. Although prostate cancer responds effectively to orchitectomy or antiandrogen therapy when detected at an early stage, over time, the residual androgen-insensitive cells recolonize, expand, and ultimately establish a hormone-resistant state that often results in fatality. It would be useful, therefore, to have a cancer treatment which could prevent the proliferation of prostate cancer and maintain it in a dormant state. The incidence of gastric cancer has fallen in most countries but it is still the most common form of cancer in many countries of East Asia, including China. Globally, gastric cancer is the second most frequent cause of cancer death and it is estimated that in 1990, there were almost 800,000 new cases and about 630,000 deaths. Similarly, esophageal cancer, the eighth most common cancer worldwide and responsible for 316,000 new cases and 286,000 deaths in 1990, is also very common in China and other Asian countries. Both of these cancers, and especially esophageal cancer, have low survival rates and thus it would be beneficial to have an alternative treatment approach for these types of cancers. Traditionally, the focus of cancer research has been in developing therapies and treatments for patients already afflicted with the disease. However, over the last few decades, new insights into the development of cancer as a disease have been gained. It is now understood that cancer is not the result of a single initiation event but of a gradual, multi-step process characterized by a period of several years between the initiation event and the onset of invasive or metastatic disease. In general, the process of carcinogenesis can be divided into three phases: initiation, promotion, and progression. In initiation, a fixed genetic mutation results from the interaction of a carcinogen with DNA. The extent of the molecular change depends on a number of factors including the nature of the carcinogen, the rate and type of carcinogenic metabolism and the response of the DNA repair systems. The next phase, promotion, may occur over extended periods of time and is characterized by the proliferation of the altered cells. This phase may be affected by agents that alter growth rates. During the final phase, progression, genetic and phenotypic changes occur which ultimately cause the development of premalignant lesions into invasive cancer. The multi-step nature of carcinogenesis suggests the possibility of intervention at a precancerous state. This is the basis for chemoprevention, which refers to the use of natural or synthetic agents to prevent the development of cancer, either by blocking the DNA damage that initiates the carcinogenesis process or by arresting/regressing existing pre-malignant lesions. Since the mid-1950s, research has been directed at finding compounds with potential chemopreventive properties. The search for these agents has demonstrated a unique challenge. Chemopreventive agents must have low toxicity and be relatively free of side effects because they are intended for administration to healthy people over long periods of time. This is in direct contrast to chemotherapy drugs, such as cis platinum or paclitaxel (Taxol™), which are used as chemotherapeutic agents to treat people already afflicted with cancer. Chemotherapeutic agents are chosen for their ability to kill tumor cells but because they are also toxic to healthy cells, they usually cause harmful side effects. One of the major sources of potential chemopreventive agents is plants. For example, consumption of cruciferous vegetables, such as broccoli, cauliflower and cabbage is associated with a lower risk of various cancers. Fruits and vegetables contain a number of potentially active chemopreventive compounds, such as carotenoids, dithiolthiones and isothiocyanates. They are capable of inhibiting the development of tumors of the lungs, colon, mammary glands and bladder in laboratory animals. Three proof-of-principle clinical trials suggest that chemoprevention might be an effective strategy to control lung cancer. A study by Hong and co-workers in the United States showed that in patients with cured head and neck cancer, high dose 13-cis-retinoic acid for 12 months was more effective than placebo in preventing second primary cancers in the upper aerodigestive tract. However, 13-cis-retinoic acid at this dosage carries unacceptable toxicity for use in the general population. Another study by Pastorino and co-workers in Europe showed that retinol palmitate in a dose of 300,000 Units per day for 12 months was more effective than placebo in preventing second primary lung cancer. A third study in China found that daily doses of a combination of vitamins and minerals consisting of betaarotene, vitamin E and selenium resulted in a 21% decrease in stomach cancer deaths in high-risk people in China. However, subsequent phase III clinical trials using beta-carotene or retinal (the Alpha-Tocopherol, Beta-Carotene Trial, the Beta-Carotene and Retinol Efficacy Trial, and the EUROSCAN study) failed to show a reduction in lung cancer incidence in high-risk individuals, such as heavy smokers with or without exposure to asbestos, compared to placebo. In fact, the use of beta-carotene in those who continued to smoke during the study was found to increase the risk of lung cancer. Several reasons were postulated to explain why chemopreventive treatment with retinoids was ineffective or even harmful in active smokers. There may be adverse interactions between tobacco carcinogens and the chemopreventive agent. Beta-carotene, for example, is a pro-oxidant at high arterial oxygen tension. It can enhance conversion of benzo[A]pyrene to the ultimate carcinogen as well as inducing cytochrome P450. Another reason for the lack of effect in active smokers is that ongoing tobacco carcinogen exposure may counteract the effect of the chemopreventive agent. A number of chemopreventive agents are currently under clinical investigation. Examples of these include fenretinide, selenium, inhaled budesonide, COX-2 inhibitors, farnesyl transferase inhibitors, lipoxygenase inhibitors, EGF-kinase inhibitors and green tea. Although promising, it remains to be shown if these agents can be shown to be useful in ongoing clinical trials. The best example to-date that chemoprevention can prevent cancer is Tamoxifen. Tamoxifen is an estrogen antagonist. In women at high risk of breast cancer, the Breast Cancer Prevention Trial showed a 49% decrease in invasive cancer and a 50% decrease in non-invasive breast cancer with Tamoxifen versus placebo (J Natl Cancer Inst 1998; 90:1371-88). In addition, there was a decrease in the incidence of fractures due to osteoporosis. However, there was a slight increase in the risk of endometrial cancer, deep venous thrombosis and pulmonary embolism. More selective estrogen-receptor modulators such as Raloxifene, are being tested against Tamoxifen to determine if these agents may have similar chemopreventive effect but fewer side effects than Tamoxifen. A variety of Chinese herbs have been used for centuries to treat different diseases. The great majority of these are empirical, open, non-randomized studies without placebo control groups. Although some of these herbs have been used to treat patients with cancer, they are not considered to be disease specific. Rather, they are used for “dispersing heat, detoxification, improving stasis and removing mass”. Herbs such as Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz , and Dioscorea bulbifera are known to have properties that may be useful for the prevention and treatment of cancers. One such composition is known as ZSP or Zeng Sheng Ping; however, the exact formulation of the composition is not known. European Patent application 93 121109.8 describes a composition comprising Sophora tonkinensis Gapnep 42 mg, Polygonum bistorta L. 42 mg, Prunella vulgaris L. 42 mg, Sonchus brachyotus DC 42 mg, Dictamnus dasycarpus Turcz 21 mg, and Dioscorea bulbifera 10 mg which was useful for the treatment of patients with mouth, esophagus or digestive tract cancers. It is well known that a chemopreventive agent that works in one organ may not work in the other organ. For example Tamoxifen, as discussed above, has been used in the treatment of breast cancer, but has not been found to be effective in any other cancers. Likewise, there is no evidence that other promising agents for preventing breast cancer, such as raloxifene and anastrozole, prevent other cancers. Therefore, persons would not predict that the composition described in the above referenced European Patent application, which was effective for treating esophagus cancer, would also show activity in other organs such as lung, prostate or breast. There is, thus, a need to determine other uses for this herbal composition and other related herbal compositions. |
<SOH> SUMMARY OF THE INVENTION <EOH>Thus, according to the present invention there is provided a composition comprising herbs for uses in treating or preventing a variety of medical conditions. Thus, according to this embodiment of the invention, there is provided a composition comprising a mixture of at least three different herbs selected from the group consisting of herbs identified in this invention as: Herb A, Herb B, Herb C, Herb D, Herb E and Herb F; wherein Herb A is selected from the group consisting of: Sophora tonkinensis ( Sophora subprostrata ) Belamcanda chinensis Scrophularia ningpoensis Isatis tinctoria Isatis indigotica and Baphicacanthus cusia; Herb B is selected from the group consisting of: Polygonum bistorta Polygonum lapidosum Polygonum viviparum Polygonum manshuriense Polygonum alopecuroides Polygonum sphaerostachyum Andrographis paniculata Taraxacum mongolicum and Chrysanthemun indicum; Herb C is selected from the group consisting of: Prunella vulgaris Artemissia capillaris Gardenia jasminoides Rosa rugosa and Lophatherum gracile; Herb D is selected from the group consisting of: Sonchus brachyotus Patrinia scabiosaefolia Patrinia villosa Sonchus arvensis Thlaspi arvense Portulaca oleracea and Pulsatilla chinensis; Herb E is selected from the group consisting of: Dictamnus dasycarpus Kochia scoparia Sophora flavescens and Heydyotis diffusa and Herb F is selected from the group consisting of: Dioscorea bulbifera Panax notoginseng Bletilla striata Nelumbo nucifera Polygonum bistorta Cephalanoplos segetum Cirsium japonicum Sophora japonica Typha angustifolia , and Rubia cordifolia ; wherein said compostions is used as chemopreventive and therapeutic agents. In one example of this invention, there is provided a method of preventing or treating cancer by administering to a patient in need thereof an effective amount of a composition as defined above. In a further example of this embodiment of the invention, there is provided a method of treating Helicobacter pylori infection by administering to a patient in need thereof an effective amount of a composition as defined above. In yet a further example of this embodiment of the invention, there is provided a method of treating or reducing the reoccurrence of cancer by administering to a patient in need thereof an effective amount of a composition as defined above. In yet a further example of this embodiment of the invention, there is provided a method of treating or preventing cancer by administering to a patient in need thereof an effective amount of a composition as defined above, as adjuncts to conventional surgery, chemotherapy or radiotherapy treatments. In a further example of this invention, there is provided a method of treating atrophic gastritis by administering to a patient in need thereof an effective amount of a composition as defined above. In a further example of this embodiment of the invention, there is provided a method of treating or preventing a chronic inflammatory condition by administering to a patient in need thereof an effective amount of a composition as defined above. In yet a further example of this embodiment of the invention, there is provided a method of treating or preventing cardiovascular disease by administering to a patient in need thereof an effective amount of a composition as defined above. In yet a further example of this embodiment of the invention, there is provided a method of treating or preventing cerebral vascular disease by administering to a patient in need thereof an effective amount of a composition as defined above. |
Stereophonic Device for Headphones and Audio Signal Processing Program |
A stereophonic device for headphones to which a monophonic signal or a stereophonic signal is inputted comprises an uncorrelating processing unit for reducing the correlation between two signals obtained by dividing the inputted monophonic signal into two channels or two signals constituting the inputted stereophonic signal, a reflected sound adding processing unit for adding a reflected sound, and a sound image localizing processing unit for controlling the position where a sound image is localized. |
1. In a stereophonic device for headphones to which a monophonic signal or a stereophonic signal is inputted, a stereophonic device for headphones, comprising: an uncorrelating processing unit for reducing the correlation between two signals obtained by dividing the inputted monophonic signal into two channels or two signals constituting the inputted stereophonic signal; a reflected sound adding processing unit for adding a reflected sound; and a sound image localizing processing unit for controlling the position where a sound image is localized. 2. An audio signal processing program used for a stereophonic device for headphones to which a monophonic signal or a stereophonic signal is inputted, wherein a computer is caused to perform: uncorrelating processing for reducing the correlation between two signals obtained by dividing the inputted monophonic signal into two channels or two signals constituting the inputted stereophonic signal; reflected sound adding processing for adding a reflected sound; and sound image localizing processing for controlling the position where a sound image is localized. 3. In a stereophonic device for headphones to which front signals for two or more channels and surround signals for two or more channels are inputted, a stereophonic device for headphones, characterized in that there are provided, with respect to each of the inputted front signal and the inputted surround signal, an uncorrelating processing unit for reducing the correlation between the signals, a reflected sound adding processing unit for adding a reflected sound, and a sound image localizing processing unit for controlling the position where a sound image is localized. 4. A sound signal processing program used for a stereophonic device for headphones to which front signals for two or more channels and surround signals for two or more channels are inputted, comprising a program for causing a computer to subject the inputted front signal to uncorrelating processing for reducing the correlation between the signals, reflected sound adding processing for adding a reflected sound, and sound image localizing processing for controlling the position where a sound image is localized, and a program for causing the computer to subject the inputted surround signal to uncorrelating processing for reducing the correlation between the signals, reflected sound adding processing for adding a reflected sound, and sound image localizing processing for controlling the position where a sound image is localized. |
<SOH> BACKGROUND ART <EOH>When music is reproduced using normal headphones, a sound image is localized in the head of a listener (in-head localization), so that a sound field having a spreading feeling cannot be reproduced. An object of the present invention is to provide a stereophonic device for headphones in which a sound field having a spreading feeling can be reproduced and an audio signal processing program. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is a block diagram showing the configuration of a stereophonic device for headphones to which a monophonic signal or a stereophonic signal is inputted. FIGS. 2 a and 2 b are schematic views showing the filter characteristics of a first FIR digital filter constituting a left signal-uncorrelating processing unit 3 a and the filter characteristics of a second FIR digital filter constituting a right signal-uncorrelating processing unit 3 b. FIG. 3 is a block diagram showing a conventional basic sound image localizing processing circuit. FIG. 4 is a schematic view for explaining a method of calculating the characteristics of a sound image localization filter using a head related transfer function. FIG. 5 is an electrical diagram showing the configuration of a stereophonic device for headphones to which front signals for three or more channels and surround signals for two channels are inputted. detailed-description description="Detailed Description" end="lead"? |
Herbal compositions useful as chemopreventive and therapeutic agents |
Composition derived from traditional Chinese herbal medicines, medicinal plants and extracts thereof, are provided. These compositions can be used as chemopreventive and therapeutic agents. |
1-8. (canceled) 9. A composition comprising a mixture of at least three different herbs selected from the group consisting of Herb A, Herb B, Herb C, Herb D, Herb E and Herb F, wherein Herb A is selected from the group consisting of: Sophora tonkinensis Belamcanda chinensis Scrophularia ningpoensis. Isatis tinctoria Isatis indigotica and Baphicacanthus cusia; Herb B is selected from the group consisting of: Polygonum bistorta Polygonum lapidosum. Polygonum viviparum Polygonum manshuriense Polygonum alopecuroides Polygonum sphaerostachyum Andrographis paniculata Taraxacum mongolicum and Chrysanthemun indicum; Herb C is selected from the group consisting of: Prunella vulgari Artemissia capillaris Gardenia jasminoides Rosa rugosa and Lophatherum gracile; Herb D is selected from the group consisting of: Sonchus brachyotus Patrinia scabiosaefolia Patrinia villosa Sonchus arvensis Thlaspi arvense Portulaca oleracea and Pulsatilla chinensis; Herb E is selected from the group consisting of: Dictamnus dasycarpus Kochia scoparia Sophora flavescens and Heydyotis diffusa; and Herb F is selected from the group consisting of: Dioscorea bulbifera Panax notoginseng Bletilla striats Nelumbo nucifers Polygonum bistorta Cephalanoplos segetum Cirsium japonicum. Sophora japonica. Typha angustfolia and Rubia cordifolia.; and wherein the composition does not comprise more than 5 herbs selected from the group consisting of Sophora tonkinesis (Sophora subprostata), Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus and Dioscorea bulbifera. 10. The composition of claim 9, wherein one of each three herbs is different from at least one of: Herb A, Herb B, Herb C, Herb D, Herb E and Herb F. 11. The composition of claim 9, wherein Herb A is selected from the group consisting of: Belamcanda chinensis Scrophularia ningpoensis. Isatis tinctoria Isatis indigotica and Baphicacanthus cusia; Herb B is selected from the group consisting of: Polygonum lapidosum. Polygonum viviparum Polygonum manshuriense Polygonum alopecuroides Polygonum sphaerostachyum Andrographis paniculata Taraxacum mongolicum and Chrysanthemun indicum; Herb C is selected from the group consisting of: Artemissia capillaris Gardenia jasminoides Rosa rugosa and Lophatherum gracile; Herb D is selected from the group consisting of: Patrinia scabiosaefolia Patrinia villosa Sonchus arvensis Thlaspi arvense Portulaca oleracea and Pulsatilla chinensis; Herb E is selected from the group consisting of: Kochia scoparia Sophora flavescens and Heydyotis diffusa; and Herb F is selected from the group consisting of: Panax notoginseng Bletilla striats Nelumbo nucifers Cephalanoplos segetum Cirsium japonicum. Typha angustfolia and Rubia cordifolia. 12. The composition of claim 9, wherein the composition comprises three herbs, one of which is selected from each of Herb A, Herb B, Herb C, Herb D or Herb E and wherein each is present in an amount from about 9% to about 57%. 13. The composition of claim 9, wherein the composition comprises four herbs, one of which is selected from each of Herb A, Herb B, Herb C, Herb D or Herb E, and wherein each is present in an amount from about 6% to about 43%. 14. The composition of claim 9, wherein the composition comprises four herbs, the first three are selected from the group consisting of Herb A, Herb B, Herb C and Herb D and are present in an amount from about 7% to about 57% and the fourth is selected from Herb E and is present in an amount from about 3.5% to about 28.5%. 15. The composition of claim 9, wherein the composition comprises five herbs, one of which is selected from each of Herb A, Herb B, Herb C, Herb D or Herb E, and wherein each is present in an amount from about 5% to about 35%. 16. The composition according to claim 9, wherein the composition comprises five herbs, and wherein the first four herbs are selected from the group consisting of Herb A, Herb B, Herb C and Herb D and are present in an amount from about 6% to about 38% and the fifth herb is selected from Herb E and is present in an amount from about 3% to about 19%. 17. The composition according to claim 9, wherein the composition comprises six herbs, and wherein the first five herbs are selected from the group consisting of Herb A, Herb B, Herb C, Herb D and Herb E wherein the herbs are present in an amount from about 5% to about 31% and the sixth herb is selected from Herb F and is present in an amount from about 2.5% to about 17.5%. 18. The composition according to claim 9, wherein the composition comprises six herbs, and wherein the first four herbs are selected from the group consisting of Herb A, Herb B, Herb C and Herb D and are present in an amount from about 5% to about 38% and the fifth is selected form Herb E and is present in an amount from about 2.5% to about 19% and the sixth herb is selected from Herb F and is present in an amount from about 1.75% to about 19%. |
<SOH> BACKGROUND OF THE INVENTION <EOH>For the past twenty-five years there has been significant progress in the field of cancer research; however, in spite of these positive results, the mortality rate for the most common cancers still remains high. Indeed, the goal of the National Cancer Institute of a fifty percent reduction in overall cancer mortality by the year 2000 has not been met. The term “cancer” is a general one referring to more than 100 forms of the disease which may manifest itself in almost every tissue type of the body. Of the myriad forms of cancer, lung cancer is the most common cause of death worldwide, followed by stomach cancer. Other common forms of cancer include cancers of the colon, rectum, breast, prostate, mouth and esophagus. Lung cancer imposes an enormous burden on health care. The World Health Report 2000 estimates that lung cancer has resulted in 860,000 deaths among men and 333,000 deaths among women per year, and it is the leading cause of cancer deaths worldwide. In the United States and Canada, more people are dying from lung cancer than from breast cancer, colorectal cancer and prostate cancer combined. In addition, the incidence of lung cancer in women is rising at an average annual rate of 7% which is the most rapid rate of increase for any cancer. The most dominant cause of lung cancer is tobacco use, but occupational and environmental exposure to various other carcinogenic substances can also influence disease development. In long-term smokers, the risk of lung cancer never returns to the “baseline” level of a never-smoker, even years after smoking cessation. With a large reservoir (100 million in the United States and Canada alone) of current and former smokers, who are at risk, lung cancer will continue to be a major health problem for at least several more decades even if current efforts to curb tobacco smoking were successful. The overall five-year survival rate of lung cancer is less than 15%. Despite advances in modern medicine, the survival rate has not improved substantially over the last two decades. A different approach is therefore needed to control lung cancer. Prostate cancer is the most commonly diagnosed male malignancy in the United States and the second leading cause of cancer death. It is estimated that in the year 2000, there will be 180,400 new cases and 31,900 deaths caused by prostate cancer. Although prostate cancer responds effectively to orchitectomy or antiandrogen therapy when detected at an early stage, over time, the residual androgen-insensitive cells recolonize, expand, and ultimately establish a hormone-resistant state that often results in fatality. It would be useful, therefore, to have a cancer treatment which could prevent the proliferation of prostate cancer and maintain it in a dormant state. The incidence of gastric cancer has fallen in most countries but it is still the most common form of cancer in many countries of East Asia, including China. Globally, gastric cancer is the second most frequent cause of cancer death and it is estimated that in 1990, there were almost 800,000 new cases and about 630,000 deaths. Similarly, esophageal cancer, the eighth most common cancer worldwide and responsible for 316,000 new cases and 286,000 deaths in 1990, is also very common in China and other Asian countries. Both of these cancers, and especially esophageal cancer, have low survival rates and thus it would be beneficial to have an alternative treatment approach for these types of cancers. Traditionally, the focus of cancer research has been in developing therapies and treatments for patients already afflicted with the disease. However, over the last few decades, new insights into the development of cancer as a disease have been gained. It is now understood that cancer is not the result of a single initiation event but of a gradual, multi-step process characterized by a period of several years between the initiation event and the onset of invasive or metastatic disease. In general, the process of carcinogenesis can be divided into three phases: initiation, promotion, and progression. In initiation, a fixed genetic mutation results from the interaction of a carcinogen with DNA. The extent of the molecular change depends on a number of factors including the nature of the carcinogen, the rate and type of carcinogenic metabolism and the response of the DNA repair systems. The next phase, promotion, may occur over extended periods of time and is characterized by the proliferation of the altered cells. This phase may be affected by agents that alter growth rates. During the final phase, progression, genetic and phenotypic changes occur which ultimately cause the development of premalignant lesions into invasive cancer. The multi-step nature of carcinogenesis suggests the possibility of intervention at a precancerous state. This is the basis for chemoprevention, which refers to the use of natural or synthetic agents to prevent the development of cancer, either by blocking the DNA damage that initiates the carcinogenesis process or by arresting/regressing existing pre-malignant lesions. Since the mid-1950s, research has been directed at finding compounds with potential chemopreventive properties. The search for these agents has demonstrated a unique challenge. Chemopreventive agents must have low toxicity and be relatively free of side effects because they are intended for administration to healthy people over long periods of time. This is in direct contrast to chemotherapy drugs, such as cis platinum or paclitaxel (Taxol™), which are used as chemotherapeutic agents to treat people already afflicted with cancer. Chemotherapeutic agents are chosen for their ability to kill tumor cells but because they are also toxic to healthy cells, they usually cause harmful side effects. One of the major sources of potential chemopreventive agents is plants. For example, consumption of cruciferous vegetables, such as broccoli, cauliflower and cabbage is associated with a lower risk of various cancers. Fruits and vegetables contain a number of potentially active chemopreventive compounds, such as carotenoids, dithiolthiones and isothiocyanates. They are capable of inhibiting the development of tumors of the lungs, colon, mammary glands and bladder in laboratory animals. Three proof-of-principle clinical trials suggest that chemoprevention might be an effective strategy to control lung cancer. A study by Hong and co-workers in the United States showed that in patients with cured head and neck cancer, high dose 13-cis-retinoic acid for 12 months was more effective than placebo in preventing second primary cancers in the upper aerodigestive tract. However, 13-cis-retinoic acid at this dosage carries unacceptable toxicity for use in the general population. Another study by Pastorino and co-workers in Europe showed that retinol palmitate in a dose of 300,000 Units per day for 12 months was more effective than placebo in preventing second primary lung cancer. A third study in China found that daily doses of a combination of vitamins and minerals consisting of beta-carotene, vitamin E and selenium resulted in a 21% decrease in stomach cancer deaths in high-risk people in China. However, subsequent phase III clinical trials using beta-carotene or retinal (the Alpha-Tocopherol, Beta-Carotene Trial, the Beta-Carotene and Retinol Efficacy Trial, and the EUROSCAN study) failed to show a reduction in lung cancer incidence in high-risk individuals, such as heavy smokers with or without exposure to asbestos, compared to placebo. In fact, the use of beta-carotene in those who continued to smoke during the study was found to increase the risk of lung cancer. Several reasons were postulated to explain why chemopreventive treatment with retinoids was ineffective or even harmful in active smokers. There may be adverse interactions between tobacco carcinogens and the chemopreventive agent. Beta-carotene, for example, is a pro-oxidant at high arterial oxygen tension. It can enhance conversion of benzo[A]pyrene to the ultimate carcinogen as well as inducing cytochrome P450. Another reason for the lack of effect in active smokers is that ongoing tobacco carcinogen exposure may counteract the effect of the chemopreventive agent. A number of chemopreventive agents are currently under clinical investigation. Examples of these include fenretinide, selenium, inhaled budesonide, COX-2 inhibitors, farnesyl transferase inhibitors, lipoxygenase inhibitors, EGF-kinase inhibitors and green tea. Although promising, it remains to be shown if these agents can be shown to be useful in ongoing clinical trials. The best example to-date that chemoprevention can prevent cancer is Tamoxifen. Tamoxifen is an estrogen antagonist. In women at high risk of breast cancer, the Breast Cancer Prevention Trial showed a 49% decrease in invasive cancer and a 50% decrease in non-invasive breast cancer with Tamoxifen versus placebo (J Natl Cancer Inst 1998; 90:1371-88). In addition, there was a decrease in the incidence of fractures due to osteoporosis. However, there was a slight increase in the risk of endometrial cancer, deep venous thrombosis and pulmonary embolism. More selective estrogen-receptor modulators such as Raloxifene, are being tested against Tamoxifen to determine if these agents may have similar chemopreventive effect but fewer side effects than Tamoxifen. A variety of Chinese herbs have been used for centuries to treat different diseases. The great majority of these are empirical, open, non-randomized studies without placebo control groups. Although some of these herbs have been used to treat patients with cancer, they are not considered to be disease specific. Rather, they are used for “dispersing heat, detoxification, improving stasis and removing mass”. Herbs such as Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz , and Dioscorea bulbifera are known to have properties that may be useful for the prevention and treatment of cancers. One such composition is known as ZSP or Zeng Sheng Ping; however, the exact formulation of the composition is not known. European Patent application 93 121109.8 describes a composition comprising Sophora tonkinensis Gapnep 42 mg, Polygonum bistorta L. 42 mg, Prunella vulgaris L. 42 mg, Sonchus brachyotus DC 42 mg, Dictamnus dasycarpus Turcz 21 mg, and Dioscorea bulbifera 10 mg which was reported to be useful for the treatment of patients with mouth, esophagus or digestive tract cancers. Thus, there is a need to develop other herbal remedies for the treatment and prophylaxis of common cancers, and for other therapeutic uses. |
<SOH> SUMMARY OF THE INVENTION <EOH>Thus, according to the present invention there is provided a composition comprising herbs. Thus, according to this embodiment of the invention, there is provided a composition comprising a mixture of at least three different herbs selected from the group consisting of herbs, which for the purpose of this invention have been designated as: Herb A, Herb B, Herb C, Herb D, Herb E and Herb F. In the composition defined in EPO 93121109.8 the herb corresponding to Herb A was Sophora tonkinensis ( Sophora subprostrata ). According to the present invention it has been found that any one of the following herbs can be used in place of Sophora tonkinensis: Belamcanda chinensis Scrophularia ningpoensis. Isatis tinctoria Isatis indigotica or Baphicacanthus cusia Bremek. In the composition defined in EPO 93121109.8 the herb corresponding to Herb B was Polygonum bistorta . According to the present invention it has been found that any one of the following herbs can be used in place of Polygonum bistorta: Polygonum lapidosum Polygonum viviparum Polygonum manshuriense Polygonum alopecuroides Polygonum sphaerostachyum Andrographis paniculata Taraxacum mongolicum or Chrysanthemun indicum. In the composition defined in EPO 93121109.8 the herb corresponding to Herb C was Prunella vulgaris . According to the present invention it has been found that any one of the following herbs can be used in place of Prunella vulgaris: Artemissia capillaris Gardenia jasminoides Rosa rugosa or Lophatherum gracile. In the composition defined in EPQ 93121109.8 the herb corresponding to Herb D was Sonchus brachyotus . According to the present invention it has been found that any one of the following herbs can be used in place of Sonchus brachyotus: Patrinia scabiosaefolia Patrinia villosa Sonchus arvensis Thlaspi arvense Portulaca oleracea or Pulsatilla chinensis. In the composition defined in EPO 93121109.8 the herb corresponding to Herb E was Dictamnus dasycarpus . According to the present invention it has been found that any one of the following herbs can be used in place of Dictamnus dasycarpus: Kochia scoparia Sophora flavescens or Heydyotis diffusa. In the composition defined in EPO 93121109.8 the herb corresponding to Herb F was Dioscorea bulbifera . According to the present invention it has been found that any one of the following herbs can be used in place of Dioscorea bulbifera: Panax notoginseng Bletilla striata Nelumbo nucifera Polygonum bistorta Cephalanoplos segetum Cirsium japonicum Sophora japonica Typha angustifolia . or Rubia cordifolia. Further according to the present invention there is provided a use of said composition as chemopreventive and therapeutic agents. detailed-description description="Detailed Description" end="lead"? |
Method for producing a coating and composition for crosslinkable coatings |
The invention concerns a method for producing a coating having high hardness, impact resistance and chemical attack resistance, characterised in that it consists in: applying on a substrate, simultaneously or successively: A) a polymer composition containing hydroxyl groups; B) an amine-formaldehyde type resin composition; C) a polyisocyanate composition containing at least 30 mol % of compounds comprising at least a biuret group; D) optionally the usual additives; and heating said substrate to a temperature enabling said constituents to be crosslinked. |
1. A method for producing a coating having a high hardness, a high impact strength and a high resistance to chemical attack, which comprises the application, to a substrate, of a blend for simultaneous or successive addition, comprising: A) a composition of a polymer containing hydroxyl groups; B) an amine-formaldehyde-type resin composition; C) a polyisocyanate that include containing at least 30 mol % of compounds that include at least one biuret group; and D) optionally, standard additives; and the heating of said substrate to a temperature allowing said components to be crosslinked. 2. The method as claimed in claim 1, wherein at least 10 mol % of the isocyanate functional groups are blocked by a monofunctional blocking agent. 3. The method as claimed in claim 1, wherein the blocking agent comprises heterocyclic nitrogen compounds. 4. The method as claimed in claim 3, wherein the blocking agent is a pyrazole, optionally substituted with one or more substituents. 5. The method as claimed in claim 4, wherein the blocking agent is 3,5-dimethylpyrazole. 6. The method as claimed in claim 1, wherein polymer (A) is an acrylic polyol having a hydroxyl content of between 1 and 5 g/100 g of polymer solids content. 7. The method as claimed in claim 1, wherein polymer (A) is an acrylic polyol having a molecular weight of between 1 000 and 5 000. 8. The method as claimed in claim 1, wherein constituent (B) is a melamine-formaldehyde resin. 9. The method as claimed in claim 1, wherein component (C) is the product obtained from polycondensation of an aliphatic or cycloaliphatic diisocyanate or triisocyanate. 10. The method as claimed in claim 7, wherein component (C) is the product obtained from polycondensation of a diisocyanate. 11. The method as claimed in claim 1, wherein the solids content of component (A) is between 10 and 60% with respect to the weight of components (A), (B), (C) and (D). 12. The method as claimed in claim 1, wherein the solids content of component (D) is between 0 and 65% with respect to the weight of components (A), (B), (C) and (D). 13. The method as claimed in claim 1, wherein component (C) comprises at least 50% of polyisocyanate compounds that include at least one biuret group with respect to the total weight of the polyisocyanate compounds. 14. The method as claimed in claim 1, wherein component (C) comprises at least 15% by weight of compounds of formula (I): in which R1, R2 and R3, which are identical or different, are linear, branched or cyclic C1-C20 hydrocarbon chains that optionally comprise an isocyanate functional group. 15. The method as claimed in claim 1, wherein the ratio of isocyanate functional groups to hydroxyl functional groups is less than 3. 16. A coating composition, which comprises: A) from 20 to 50% by weight of solids content of a polymer containing hydroxyl groups; B) from 3 to 20% by weight of solids content of a resin of the amine-formaldehyde type; C) from 5 to 20% by weight of solids content of a polyisocyanate composition comprising at least 50 mol % of one or more biuret groups, in which at least 10 mol % of the isocyanate groups are protected using a monofunctional blocking agent; D) from 0 to 30% by weight of solids content of various additives for the coating; and E) from 10 to 20% by weight of one or more solvents. 17. The composition as claimed in claim 16, wherein the blocking agent comprises heterocyclic nitrogen compounds. 18. The composition as claimed in claim 16, wherein the blocking agent is a pyrazole optionally substituted with one or more substituents. 19. The composition as claimed in claim 16, wherein the blocking agent is 3,5-dimethylpyrazole. 20. The composition as claimed in claim 16, wherein polymer (A) is an acrylic polyol having a hydroxyl content of between 1 and 5 g/100 g of polymer solids content. 21. The composition as claimed in claim 16, wherein polymer (A) is an acrylic polyol having a molecular weight of between 30 000 and 5 000. 22. The composition as claimed in claim 16, wherein component (B) is a melamine-formaldehyde resin. 23. The composition as claimed in claim 16, wherein component (C) is the product obtained from polycondensation of an aliphatic or cycloaliphatic diisocyanate or triisocyanate. 24. The composition as claimed in claim 23, wherein component (C) is the product obtained from polycondensation of a diisocyanate. 25. The composition as claimed in claim 16, wherein component (C) comprises at least 50% of polyisocyanate compounds that include at least one biuret group with respect to the total weight of the polyisocyanate compounds. 26. The composition as claimed in claim 16, wherein component (C) comprises at least 15% by weight of compounds of formula (I): in which R1, R2 and R3, which are identical or different, are linear, branched or cyclic C1-C20 hydrocarbon chains that optionally comprises an isocyanate functional group. 27. The composition as claimed in claim 16, wherein the ratio of isocyanate functional groups to hydroxyl functional groups is less than 3. |
Electro-optic modulator |
An electro-optic device includes a semiconducting layer in which is formed a waveguide, a modulator formed across the waveguide comprising a p-doped region to one side and an n-doped region to the other side of the waveguide, wherein at least one of the doped regions extends from the base of a recess formed in the semiconducting layer. In this way, the doped regions can extend further into the semiconducting layer and further hinder escape of charge carriers without the need to increase the diffusion distance of the dopant and incur an additional thermal burden on the device. In an SOI device, the doped region can extend to the insulating layer. Ideally, both the p and n-doped regions extend from the base of a recess, but this may be unnecessary in some designs. Insulating layers can be used to ensure that dopant extends from the base of the recess only, giving a more clearly defined doped region. The (or each) recess can have non-vertical sides, such as are formed by v-groove etches, A combination of a vertical sidewall at the base of the recess and a non-vertical sidewall at the opening could be used. |
1. An electro-optic device including a semiconductor layer in which is formed a waveguide, a modulator formed across the waveguide comprising a doped region on either side, a lower confinement structure for charge carriers beneath the waveguide, lateral confinement structures for charge carriers on either side of the waveguide which extend to the lower confinement structure, at least one of the lateral confinement structures being the doped region to that side of the waveguide, the doped region extending to the lower confinement structure. 2. An electro-optic device according to claim 1 in which both lateral confinement structures are provided by the doped regions on either side of the waveguide. 3. An electro-optic device according to claim 1 in which the semiconducting layer is formed on an insulating layer supported on a substrate. 4. An electro-optic device according to claim 1 in which the insulating layer is the lower confinement structure. 5. An electro-optic device according to claim 4 in which the lateral confinement structures extend from the base of a recess in the semiconducting layer to the insulating layer. 6. An electro-optic device according to claim 1 in which one or both doped regions extend from the base of a recess formed in the semiconducting layer. 7. An electro-optic device according to claim 5, in which each lateral confinement structure and/or doped region extends from the base only of a said recess. 8. An electro-optic device according to claim 1 in which the waveguide is covered by an insulating layer. 9. An electro-optic device according to claim 8 in which the insulating layer extends to at least one side of a recess. 10. An electro-optic device according to claim 5 in which at least part of the depth of the or each recess has non-vertical sides. 11. An electro-optic device according to claim 1 in which the doped region to one side of the waveguide is p-type and the doped region to the other side of the waveguide is n-type. 12. An electro-optic device including a semiconducting layer in which is formed a waveguide, a modulator formed across the waveguide comprising a doped region on either side, wherein at least one of the doped regions extends from a base only of a recess formed in the semiconducting layer. 13. An electro-optic device according to claim 12 in which an insulating layer, is provided on side walls of the device to inhibit diffusion of dopant therethrough. 14. An electro-optic device according to claim 12 in which the dopant is implanted in the semiconducting layer. 15. An electro-optic device according to claim 1 in which the waveguide is a rib waveguide. 16. An electro-optic device according to claim 1 which a plurality of such lateral modulators are formed along the length of the waveguide, each being a p-i-n modulator, adjacent modulators being mutually reversed in orientation. 17. An electro-optic device according to claim 16 in which there are an even number of modulators. 18. An electro-optic device according to claim 15 in which there are four modulators. 19. An electro-optic device according to claim 1 in which the semiconducting layer comprises silicon, preferably crystalline silicon. 20. An electro-optic device including a semiconductor layer in which is formed a waveguide, a modulator formed across the waveguide comprising a doped region on either side, a lower confinement structure for charge carriers beneath the waveguide, lateral confinement structures for charge carriers on either side of the waveguide, each of which extends from the base of a recess in the semiconducting layer to the lower confinement structure, at least one of the lateral confinement structures being the doped region to that side of the waveguide. 21. An electro-optic device including a semiconductor layer in which is formed a waveguide, a modulator formed across the waveguide comprising a doped region on either side, a lower confinement structure for charge carriers beneath the waveguide, lateral confinement structures for charge carriers on either side of the waveguide which extend to the lower confinement structure, at least one of the lateral confinement structures being the doped region to that side of the waveguide, the doped region extending from the base of a recess formed in the semiconducting layer, to the lower confinement structure. |
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