Device for actuating a plurality of actuators (1) in a transportation device, which has a plurality of output stages (2, 3, 4, 5) and a control circuit for actuating the output stages (2, 3, 4, 5), the output stages (2, 3, 4, 5) each connecting through the current in order to activate the actuators (1) and each output stage (2, 3, 4, 5) being connected in electrically conductive fashion to an actuator (1, 9). A plurality of output stages (2, 3, 4, 5) is additionally connected to in each case, one further actuator (1, 9) by the control circuit. The control circuit is actuated in such a way that an output stage (2, 3, 4, 5) can actuate either the first or the further actuator (1, 9) with the output stages (2, 3, 4, 5) being interconnected to one another and/or to the actuators (1, 9) in the manner of a matrix so that a plurality of row lines (6) and a plurality of column lines (7), at whose points of intersection (8) the actuators (1) are arranged, are provided.

The invention relates to a device for actuating a plurality of electric motors in a transportation device, which has a plurality of output stages and a control circuit for actuating these output stages. Each output stage is connected to an electric motor for providing a current for activating the electric motor.
The number of electronic components in the transportation device, in particular in motor vehicles, is continuously increasing. The increasing amount of power electronics in each electric motor respectively entails a proportional increase in the costs of the electronics. Because of the high density of electronics within contemporary transportation devices, in particular the retrofitting of electric motors must also be taken into account. Control circuits and power electronics have to be retrofittable for this situation if the means of transportation is to be retrofitted during its long service life. In addition, electric motors in a motor vehicle are often switched on only for a short time and in many cases this precludes the simultaneous operation of another electric motor in parallel. As a result, the multiple arrangement of expensive output stages within one motor vehicle is a waste of existing electronic resources.
A wide variety of solutions are already used in motor vehicles for actuating electric motors. Such devices relate to means of transportation such as aircraft, waterborne vessels or motor vehicles. These devices have the following design: a control circuit with a microcomputer or a logic circuit evaluates input data and signals from operator control elements and uses sensor signals to calculate the regulating variables and control variables for the means of transportation. For the actual actuation of the electric motor, output stages are used which connect through or disconnect the power current for the electric motor. Today, such output stages have power breakers in the form of transistors, thyristors or diacs. These power breakers are activated by the control circuit in accordance with the calculated control variables and regulating variables so that the current for the electric motors is connected through or disconnected according to requirements. If the current for the electric motors is connected through, they begin to rotate so that, for example, a seat is actuated and can be moved.
In the case of semiconductor switches, a matrix-like arrangement of semiconductors is known which have various semiconductor switches. European Patent EP 240805 A2 discloses a power breaking matrix such as is used in computer technology or in telecommunications. However, there is no consideration here of the generic use for actuating electric motors in means of transportation.
German Patent DE 697 05 002 T2 discloses a matrix-like actuation circuit for a plurality of lamps, in each case one output stage is connected to a row line and a column line. As a result, a plurality of lamps can be actuated with relatively few output stages. The actuation circuit is less suitable for actuating electric motors as they can be operated only in one direction if a motor vehicle battery is used for supplying power.
German Patent DE 199 10 194 C2 discloses a measuring circuit for a pressure-sensitive resistance matrix using operation measuring amplifiers which are connected to the resistor matrix. However, the circuit is not suitable for actuating electric motors.
The object of the present invention is to reduce the number of output stages in order to operate a predefined number of electric motors in both directions of rotation. In addition, when an output stage fails, it is to be possible to actuate the respective electric motor by a further alternative output stage.
This object is achieved according to the invention by using a plurality of output stages additionally connected to, in each case, one further electric motor by the control circuit. The control circuit actuates each output stage in such a way that the output stage can actuate either the first or the further electric motor with the output stages being interconnected to one another and/or to the electric motors in the manner of a matrix so that there are a plurality of row lines and a plurality of column lines, at whose points of intersection the electric motors are arranged. Using each row line and each column line, in each case two output stages are connected to power breakers which connect, in accordance with the signals of the control circuit, to a first or a second potential, in particular earth and Ubatt. As a result the actuated electric motor can be operated either in one direction or the other.
The output stages each have at least one power breaker and control the power currents in order to actuate electric motors in a means of transportation. Such output stages constitute a high cost factor within the means of transportation and it is then possible, within the scope of the teaching according to the invention, to make a saving by eliminating them because the electric motors which are arranged within a matrix can be actuated in each case by an output stage by means of the row lines and column lines. For example, two to nine electric motors can be connected to an output stage at one row line and this output stage can alternatively actuate a plurality of electric motors. Owing to the lower number of output stages, the expenditure on cooling and the installation space for the output stages within the power electronics is reduced. The power semiconductors are utilized effectively, in particular if, of the electric motors arranged in the matrix, in each case only one electric motor can be operated. Moreover, by virtue of the matrix-like arrangement and the possibility of actuating further electric motors in the matrix, the system can also be enlarged by means of further electric motors after the means of transportation has been delivered. For this purpose, all that is needed for the control circuit is new software which permits the output stage to actuate the additional electric motor.
The inventive arrangement of the electric motors within the matrix and the arrangement of the output stages at the end of the row lines or column lines permits the number of output stages to be reduced in comparison with the electric motors to be actuated. Owing to the centralization of the electric motors in matrix form it is possible to construct both the electric motors and the output stages in modular form, i.e. provide them with similar interfaces so that they can be replaced by a further module. Owing to the centralization, the control circuit can be equipped with a more complex power management system for the electric motors as they can then be arranged within one control circuit for all the electric motors. Moreover, the matrix-like structure permits the electric motors and the output stages to be supplied by means of film lines, specifically on the one hand by means of high-current film lines for supplying the electric motors with power and on the other hand by means of low-current film lines for the logic actuation of the output stages by the control circuit. The matrix-like and modular design also makes it easier for failed components to be retrofitted here as all that is necessary is to replace one module in the matrix, and at the same time the interfaces can be respectively standardized.
According to the invention, the device is constructed in such a way that in each case two output stages, which connect to a first or a second potential in accordance with the signals of the control circuit, are connected to each row line and each column line. The first potential may be the zero potential, corresponding to the negative pole of the battery in the means of transportation, while the second potential can be the positive battery voltage, for example 12 to 14 volts. If an electric motor of the matrix is then arranged between the first column line of the first row line, the electric motor is driven, for example, in the clockwise direction if the first row line conducts zero potential and the first column line conducts the positive battery potential, while the electric motor is driven in the anticlockwise direction if the first row line conducts the positive battery potential and the first column line conducts the zero potential. Two output stages, one which connects to the zero potential and one which connects to the positive battery potential, are arranged on the first column line. Thus the respective output stage can be actuated in order to make available the corresponding potential for the electric motor. As two output stages are also arranged on the first column line, one output stage can be actuated by the control circuit to connect through to a positive battery potential. If then, for example, the first row line is connected to zero potential, a further electric motor of the matrix can then be actuated in parallel with the first electric motor if the second column line also connects through the corresponding positive potential. For this purpose, the control circuit actuates the corresponding output stage of the second column line so that the latter connects through the supply current for the second electric motor. By virtue of the redundant arrangement of the two output stages per row line or column line it is possible for each of the lines to be connected alternatively to two potentials, respectively permitting the right-handed or left-handed operation of an electric motor.
The object of the present invention is, however, also achieved by a device where the electric motors are each arranged between two power supply lines with a plurality of electric motors being connected in each case to a common power supply line, and the respective other power supply connection of these electric motors being connected to different power supply lines. Each power supply line is electrically connected to, in each case, two output stages, the first output stage being connected to a first potential, and the second output stage being connected to a second potential. A circuit breaker is provided between a plurality of electric motors and in each case the assigned power supply circuit in order to prevent parallel currents as a result of electric motors which are not actuated.
The device according to the invention reduces the number of output stages for operating the electric motors. The modularization results in improved retrofittability and higher flexibility together with lower costs. Owing to the centralization of the technology, the reliability of the components and of the entire system is improved and, in addition to the reduced expenditure on components and monitoring, it is possible to exchange and replace the individual elements more easily.
The device according to the invention provides for the power-electronic output stages to be interconnected to the actuated electric motors by means of a matrix-like structure. The electric motors are arranged here between a first and a second power supply line, which are also referred to as column lines or row lines. The column lines and row lines are laid within the means of transportation and in technical practice not laid linearly and at right angles to one another. The concepts of column lines or row lines indicate however the actuation pattern of a plurality of electric motors through the various column lines and row lines. The electric motors are distributed between a predefined number of row lines m and a certain number of column lines n in such a way that in each case one power supply line is connected to a connection of the electric motor, while the other power supply line is connected to the other connection of the electric motor. For the sake of easy comprehension of the device it is possible to say that the electric motors are connected to the points of intersection between the column line and the row line. In addition, electric motors can also be arranged between two column lines or between two row lines, in which case the column lines which lie next to one another must however always be connected to different potentials so that the electric motor can be operated. For example, when the first electric motor is operating, the first column line is then at zero potential while the second column line is at positive battery potential. A combination is also possible so that individual electric motors are arranged at the points of intersection between column lines and row lines and other electric motors are connected between in each case, two column lines or, in each case, two row lines. The number of power supply lines between the electric motors is reduced as a result of the matrix-like connection of the electric motors. On each supply line, a plurality of electric motors are connected using the power supply connections provided for that purpose.
The control circuit is connected to the output stages using, for example, film flat lines or conventional lines in order to provide the actuation current for the output stages. The control circuit may have a microcontroller in which the control algorithms are stored in order to be able to operate them in accordance with the requirements in the means of transportation. This microcontroller may also contain the complete control functions of a control device.
As already described, a circuit breaker which helps to avoid parallel currents across the connection matrix is provided within the matrix. The circuit breaker permits an electric motor to be supplied with power by adding the power supply line if the voltage drop across the electric motor, which is caused by the difference in potential between the two power supply lines of the electric motor, is greater than a threshold voltage. The power breaker of the circuit breaker can switch off the flow of current in both directions. This power breaker is intended to prevent the formation of parasitic parallel mass currents across the further electric motors which are arranged within the matrix and not actuated. The circuit breaker prevents the flow of current if there is a series circuit composed of a plurality of electric motors at one row line or one column line. The circuit breaker must operate bidirectionally so that motor currents can permit or disable the left-handed or right-handed rotation of an electric motor.
One possible way of implementing the circuit breaker is what is referred to as an electronic diac. The circuit is composed of two power semiconductor switches which are each connected to the connections of the electric motor and whose other end is connected to the column line or row line. Two Schottky diodes which are connected in antiparallel generate a slight drop in voltage across the power breaker if the latter is connected to the on position. Two Zener diodes which are connected in parallel in crisscross fashion set the breakdown voltage to, for example, 6 to 9 volts so that when this breakdown voltage is exceeded the power semiconductor is switched on in order to feed the supply current to the actuated electric motor. If the breakdown voltage at the Zener diode drops below the necessary threshold voltage when an electric motor is not actuated, the circuit breaker switches off and the electric motor is no longer supplied with the corresponding power current. This ensures that only the electric motors which are actuated directly by the control circuit draw current, while the electric motors in parallel branches of the matrix-like electric motor system remain switched off if the actuation voltage, i.e. the difference in potential between the column line and row line is lower than the breakdown voltage. This electronic diac can expediently be applied to circuit boards and film lines or integrated directly into the electric motor. Owing to the matrix-like structure within the device, an error routine can be initiated if the individual power components fail. For this purpose, it is possible to provide, at those output stages which connect to the lower voltage level, a measuring shunt which has the purpose of measuring current. This measured value can be used to monitor the current of the electric motors and can serve as an overload protection for the power breakers. The registration of the measurement signals and the processing of the corresponding evaluation routine which are necessary for this purpose can then be carried out by means of the control circuit which, in the case of an excess current, switches off the respective electric motor and actuates the electric motor via an alternative output stage.
In each case two of the output stages may be combined to form what is referred to as a MOSFET half bridge, each of which half bridges are connected to the end of a power supply line. The MOSFET half bridge has, for this purpose, two MOSFET semiconductor power breakers which can be connected through by the control circuit via a corresponding actuation circuit. In order to operate a specific electric motor, the column lines and row lines which are connected to this electric motor must be connected to the potential corresponding to the direction of rotation. In this context, one power breaker of the MOSFET half bridge connects to the zero potential, while the other semiconductor switch of the MOSFET half bridge connects to the positive battery potential.
The device according to the invention provides for a matrix-like connection of the electric motors which can each be switched on by a control circuit. The electric motors are operated, for example, by means of the MOSFET half bridges in accordance with the control specifications of the control circuit. The control circuit monitors the power flux within the matrix and performs corresponding error routines if components fail. The circuit breaker in the form of the electronic diac prevents parasitic series connections within the matrix-like interconnection of the electric motors and automatically disconnects non-actuated electric motors from the supply voltage.
The device according to the invention has considerable advantages over conventional actuation circuits within a means of transportation. A number of electric motors, predefined by the requirements made of the means of transportation, may be arranged in modular fashion within the described circuit topology and actuated by means of a relatively small number of output stages. 15 electric motors can be actuated by, for example, 6 MOSFET half bridges, which, without the provided switching matrix, would require approximately 30 half bridges with the same function. However, the matrix-like arrangement also permits the number of control outputs of the control circuit to be reduced, as a result of which the number of susceptible contacts is also reduced. The reduced number of power components also reduces the expenditure on cooling. The installation volume and the weight of the control circuits is reduced. This is apparent in particular in the field of motor vehicle seats where today up to 30 electric motors are used. The reduced expenditure on components permits the reliability of the control devices to be increased.
The electric motor can also be embodied as a stepping electric motor and have a plurality of connections for power supply lines. In each case earth potential or a predefined positive potential is applied to these connections. For this purpose, the motor is connected in an electrically conductive fashion to a plurality of column lines and the output stages can then connect through the voltage in accordance with the control circuit in each case. The stepping motor can be provided, for example, in vehicle seats for setting the sitting position.
There are various possible ways of advantageously configuring and developing the teaching of the present invention. In this respect, reference is made, on the one hand, to the subordinate claims and, on the other, to the following explanation of an embodiment. One embodiment of the device according to the invention is illustrated in the drawing in which, in each case in a schematic representation,
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.

Device for actuating a plurality of electric motors


The present invention relates to a method for avoiding undesirable discoloration in polycarbonate production by catalytic removal of dissolved oxygen from phenol by

The invention relates to a process for the removal of dissolved oxygen from phenol by admixing water into the phenol, which is then passed over metals of the platinum group applied to supports in order to catalyze the reaction of hydrogen and oxygen to give water in accordance with the equation: 2H2+O2xe2x86x922H2O. The invention further relates to polycarbonate and bisphenol A that are prepared from oxygen-free phenol prepared by admixing water and subsequently passing the mixture over ion exchangers doped with platinum metal.
Phenol is an important unit in the preparation of the plastic polycarbonate. Phenol is first reacted with acetone under acid conditions to give bisphenol A. The molar ratio of the reactants phenol: acetone here is in the range of 8:1 to 14:1, preferably in the region of 12:1. Bisphenol A is then reacted with either phosgene or diphenyl carbonate to give polycarbonate in the following step.
This plastic is employed in a very wide-ranging spectrum of uses, inter alia in very demanding fields, such as in the preparation of high-quality optical materials and of compact discs and in the electronics field.
However, discoloration of the plastics often prevent their use in these applications, even when a very great effort is made to keep the quality of the starting substances at a high level.
It has now been found, surprisingly, that discoloration can be virtually completely avoided if hydrogen is added to the phenol and the mixture is then passed over a support, preferably an ion exchanger, doped with at least one metal of the platinum group.
How the discoloration arises has not yet been clarified in detail. At the moment, however, it is assumed that discoloration is caused by the nonselective action of oxygen present in the starting substances.
The invention relates to a process for the removal of dissolved oxygen from phenol by admixing hydrogen into the phenol, which is then passed over metals of the platinum group applied to supports in order to catalyze the reaction of hydrogen and oxygen to give water in accordance with the equation: 2H2+O2xe2x86x922H2O. The invention further relates to polycarbonate and bisphenol A that are prepared from oxygen-free phenol prepared by admixing hydrogen and subsequently passing the mixture over ion exchangers doped with platinum metal.
The present invention relates to a process for the catalytic removal of dissolved oxygen from phenol comprising
(a) admixing hydrogen with phenol and
(b) passing the phenol stream over ion exchangers doped with platinum group metals to catalyze the reaction 2H2+O2xe2x86x922H2O.
The platinum metals to be used according to the invention are the elements of the series ruthenium, rhodium, palladium, osmium, iridium, and platinum. Palladium and platinum are preferred for the process according to the invention.
The ion exchangers to be used according to the invention are preferably anion exchangers and can contain weakly and/or strongly basic groups. Strongly basic exchangers in the C1 form or weakly basic anion exchangers in the free base form are particularly preferred. A crosslinked polymer of ethylenically unsaturated monomers is used as the base polymer. Examples of ethylenically monounsaturated monomers are, for example, styrene, vinyltoluene, ethylstyrene, xcex1-methylstyrene, and derivatives thereof halogenated in the nucleus (such as chlorostyrene), vinylbenzyl chloride, acrylic acid and its salts and esters (particularly the methyl and ethyl esters), methacrylic acid and its salts and esters (particularly the methyl ester), and the nitriles and amides of acrylic and methacrylic acid.
The polymers are crosslinked, preferably by copolymerization with crosslinking monomers having more than one (preferably 2 or 3) copolymerizable Cxe2x95x90C double bonds per molecule. Such crosslinking monomers include, for example, poly-functional vinylaromatics, such as di or trivinylbenzenes, divinylethylbenzene, divinyltoluene, divinylxylene, divinylethylbenzene, or divinylnaphthalene; poly-functional allylaromatics, such as di- or triallylbenzenes; polyfunctional vinyl or allyl-heterocyclic compounds, such as trivinyl or triallyl cyanurate or trivinyl or triallyl isocyanurate; N,Nxe2x80x2-C1-C6alkylenediacrylamides or dimethacrylamides, such as N,Nxe2x80x2-methylenediacrylamide or -dimethacrylamide or N,Nxe2x80x2-ethylenediacrylamide or -dimethacrylamide; polyvinyl or polyallyl ethers of saturated C2-C20-polyols having 2 to 4 OH groups per molecule, such as, for example, ethylene glycol divinyl or diallyl ether or diethylene glycol divinyl or diallyl ethers; esters of unsaturated C3-C12-alcohols or saturated C2-C20-polyols having 2 to 4 OH groups per molecule, such as allyl methacrylate, ethylene glycol di(meth)acrylate, glycerol tri(meth)acrylate, or pentaerythritol tetra(meth)acrylate; divinylethyleneurea, divinylpro-pyleneurea or divinyl adipate; or aliphatic or cycloaliphatic olefins having 2 or 3isolated Cxe2x95x90C double bonds, such as hexa1,5-diene, 2,5-dimethylhexa1,5-diene, octa1,7-diene, or 1,2,4-trivinylcyclohexane. Divinylbenzene (as an isomer mixture) and mixtures of divinylbenzene and aliphatic C6-C12-hydrocarbons having 2 or 3 Cxe2x95x90C double bonds have proved to be particularly suitable crosslinking monomers.
The crosslinking monomers are in general employed in amounts of 2 to 20% by weight, preferably 2 to 12% by weight, based on the total amount of polymerizable monomers employed.
The crosslinking monomers do not have to be employed in pure form but can also be employed in the form of their technical grade mixtures of lower purity (such as, for example, divinylbenzene mixed with ethylstyrene).
The crosslinked polymers can be further processed to give anion exchangers in a known manner. The anion exchangers can be prepared on the one hand by chloromethylation (cf. U.S. Pat. Nos. 2,642,417, 2,960,480, 2,597,492, 2,597,493, 3,311,602, and 2,616,877), preferably with chloromethyl ether, and subsequent amination (cf. U.S. Pat. Nos. 2,632,000, 2,616,877, 2,642,417, 2,632,001, and 2,992,544) with ammonia, a primary amine, such as methyl or ethylamine, a secondary amine, such as dimethylamine, or a tertiary amine, such as trimethylamine or dimethylisopropanolamine, at a temperature of as a rule 25 to 150xc2x0 C.
On the other hand, the anion exchangers can be prepared by the aminomethylation process, in which (a) the crosslinked polymers are reacted with phthalimide derivatives and (b) the resulting imides are hydrated. The amidomethylation (a) can be carried out by reaction of the crosslinked polymers with N-chloromethyl-phthalimide in the presence of swelling agents for crosslinked polymers and Friedel-Crafts catalysts (DE-A 1,054,715), the phthalimide derivative being employed in amounts suitable for the desired level of substitution (0.3 to 2.0 substitutions per aromatic nucleus) of the aromatic nuclei present in the crosslinked polymer (or in an excess of up to 20%, preferably up to 10%).
Suitable swelling agents include halogenated hydrocarbons, preferably chlorinated C1-C4-hydrocarbons. The most preferred swelling agent is 1,2-dichloroethane.
Preferred Friedel-Crafts catalysts include, for example, A1C13, BF3, FeC13, ZnC12,TiC14, ZrC14, SnC4, H3PO4, HF, and HBF4. The catalysts can be employe amounts of 0.01 to 0.1 mol per mole of N-chloromethylphthalimide.
The reaction can be carried out, for example, by a procedure in which the crosslinked polymer is introduced into a solution of N-chloromethylphthalimide in a swelling agent and the reactants are allowed to act in the presence of the catalyst at elevated temperature, as a rule at 50 to 100xc2x0 C., preferably 50 to 75xc2x0 C., until the evolution of hydrogen chloride has substantially ended. This is in general the case after 2 to 20 hours. After separation of the substituted polymer and liquid reaction medium and inorganic products, it is advisable to take up the polymer in aqueous sodium chloride solution and to remove residues of swelling agent by distillation.
The hydrolysis (b) of the substituted polymer can be carried out, for example, by subsequently hydrolyzing the product that has been isolated with an approximately 5 to 40% strength by weight aqueous or alcoholic solution of an alkali, such as sodium hydroxide or potassium hydroxide, or with an approximately 5 to 50% strength by weight aqueous solution of a mineral acid, such as hydrochloric acid, hydrobromic acid, or sulfuric acid, in an autoclave at temperatures between 100 and 250xc2x0 C. On the other hand, the intermediate product can also be reacted with a 5 to 50% strength by weight aqueous or alcoholic solution of hydrazine hydrate at temperatures of 50 to 100xc2x0 C. In a preferred embodiment, the solution described last can contain other alkalis, in particular caustic alkalis, in amounts of 1 to 20% by weight. The reaction product can be isolated, washed with water and then heated with an aqueous solution of mineral acid (preferably 5 to 20% strength by weight) to bring the hydrolysis to completion.
The aminoalkyl compounds that can be obtained can be modified by alkylation. Known alkylating agents, such as, for example, methyl, ethyl, or propyl chlorides and bromides, dialkyl sulfates, alkylene oxides, halogenohydrins, polyhalogen compounds, epihalohydrins, and ethyleneimines, can be used for this purpose.
The above-mentioned alkylation of the said amino derivatives can be effected by reaction thereof with alkylating agents in molar amounts at temperatures of between 20 and 125xc2x0 C. If, for example, alkyl halides or dialkyl sulfates are used, it is advisable to add the amount of an alkaline agent, such as sodium hydroxide, calcium carbonate, magnesium oxide, and the like, required for neutralization of the hydrogen halide acids or alkylsulfuric acids formed. Secondary, tertiary, or quaternary amino derivatives or mixtures thereof are obtained depending on the amount of alkylating agent used. A mixture of formaldehyde with formic acid is another customary alkylating agent which is used in the form of an aqueous solution, if appropriate in the presence of mineral acids. The reaction can be carried out with these alkylating agents at temperatures of between 50 and 120xc2x0 C. In the latter case, tertiary amino derivatives are obtained as the sole reaction products if an excess of alkylating agent is used. The tertiary amino derivatives can be converted completely or partly into quaternary derivatives by carrying out a further reaction with alkylating agents, such as, for example, methyl chloride, at temperatures of between 10 and 120xc2x0 C.
The anion exchangers used can be in gel form or, preferably, macroporous; those based on polystyrene are preferred. Strongly basic anion exchangers in the C1 form and weakly basic anion exchangers in the free base form are particularly preferred.
Doping of the anion exchangers with platinum metals, preferably platinum or palladium, can be carried out, for example, by a procedure in which the platinum metal, preferably platinum or palladium, in a suitable salt form is taken up by the groups with ion exchange activity and is then reduced, or reducing substances are first applied and the platinum metal, preferably platinum or palladium, is then precipitated on the resin from a suitable solution. Finally, colloidally dispersed platinum metal that has already been reduced, preferably platinum or palladium, can also be taken up adsorptively by the resin from a corresponding solution or suspension.
The application process which is particularly preferred in the present invention starts from the salt form of the resin, which is first treated with a palladium salt solution (for example, 2 to 20% strength by weight Na2PdC14), the anion on the resin being exchanged for the anionic palladium complex. The palladium complex is chiefly distributed in the surface region of the resin grain, so that the regions which are distinguished by rapid kinetics are affected above all.
The reduction of the noble metal bonded ionogenically to the resin, for example, of palladium to metallic palladium, can be carried out by reducing agents that are usual for this type of reduction, such as hydrazine, hydroxylamine, hydrogen, ascorbic acid, formalin, or formic acid, in strongly alkaline solution at elevated temperature. Hydrazine or formalin is preferably used.
The noble metal content, preferably of platinum metal, of the ion exchangers to be used according to the invention is in general in the range from 0.3 to 10 g, preferably 0.5 to 1.2 g, per liter of anion exchanger.
DE-A 25 24 722 discloses the use of polystyrenes containing copper ions or cobalt ions for reduction of oxygen dissolved in water. U.S. Pat. No. 4,789,488 recommends palladium or platinum-doped anion exchangers for decreasing the oxygen content in aqueous systems with hydrogen. In addition to hydrogen, other reducing agents, such as, for example, hydrazine, have also already been described for removal of oxygen from water. Cf. F. Martinola et al., VGB Kraftwerkstechnik 64 (1984), pages 61-63. The use of metal-doped anion exchangers for simultaneous removal of oxygen and undesirable ions has also already been discussed. Cf. F. Martinola, loc. cit.
It has now been found that this process is very effective in avoiding discoloration in polycarbonate production by catalytic reduction of oxygen. The theory described above that the discoloration is to be attributed to traces of oxygen is thereby substantiated. Since phenol not only is the main component of the polyearbonate but is also present in a large excess in the preparation of bisphenol A and is at the start of the production sequence it is appropriate to use this process on this starting material.

Process for the removal of dissolved oxygen from phenol

Abstract: (a) admixing hydrogen with phenol and

Abstract: (b) passing the phenol stream over ion exchangers doped with platinum group metals.


The growth of body and/or head/cranial hair on mammalian organisms, for example humans, is modulated by administering thereto, whether topically and/or systemically, therapeutically effective amounts of at least one lipoxygenase or cyclooxygenase inhibitor, or at least one lipoxygenase or cyclooxygenase stimulator, preferably in the presence of at least one lipoxygenase/cyclooxygenase substrate or precursor thereof; when a hair-growth or hair loss-limiting response is sought to be elicited, a lipoxygenase inhibitor and/or cyclooxygenase stimulator is administered (conversely, to reduce or prevent hair growth, a lipoxygenase stimulator and/or cyclooxygenase inhibitor is administered).

1. Field of the Invention
The present invention generally relates to modifying the growth of body and/or head hair, and, more especially, to a treatment which, depending essentially on the nature of the compositions employed therefor, permits either promoting the growth and/or limiting the loss of body and/or head hair, or, contrariwise, reducing or preventing the growth of this hair.
The present invention also relates to such compositions, per se, and specific hair growth-modulating applications thereof.
2. Description of the Prior Art
It is known to the art that certain polyunsaturated fatty acids, in particular those containing 20 carbon atoms, such as arachidonic acid, dihomo-xcex3-linolenic acid, or, alternatively, eicosapentaenoic acid, may be converted, in vivo, under the action or influence of certain specific enzymes present in living cells, in particular in epithelial cells, into certain other compounds of eicosanoid type which are useful to the organism.
Thus, it too is known that the enzymes designated cyclooxygenases generate, from the various fatty acids indicated above, eicosanoids of prostaglandin and thromboxane type, and that the enzymes designated lipoxygenases are themselves responsible for the formation of eicosanoids of leukotriene type and other hydroxylated acyclic acids containing 20 carbon atoms. This same specific polyunsaturated fatty acid (or substrate) may initiate, depending on the nature of the enzyme with which it is first reacted, the formation of several different metabolites, for example prostaglandins and leukotrienes.
Polyunsaturated fatty acids, in particular C20 acids (reactive starting materials), which are known to be metabolized under the specific action of the cyclooxygenase and lipoxygenase enzymes, are generally supplied to the living organism via certain foods, in particular certain natural oils of animal or vegetable origin. This food supply may either be in a direct form (which is, for example, the case for arachidonic acid, which is present as is in egg whites), or indirectly in the form of precursor compounds (compounds which are also deemed xe2x80x9cessential fatty acids,xe2x80x9d themselves generally C18-C22 unsaturated fatty acids, such as linoleic acid, xcex1-linolenic acid and xcex3-linolenic acid) which are converted via human metabolism, according to complex mechanisms which will not be repeated here, into suitable substrates (namely, metabolizable) for cyclooxygenases and lipoxygenases.
After considerable research efforts, it has now unexpectedly and surprisingly been found that the enzymatic conversions described above, and the various reaction products resulting therefrom, exert a significant influence on the mechanisms for the growth of body and/or head hair; thus, by favoring (according to techniques more fully described below) one or the other of the two cyclooxygenase or lipoxygenase enzymatic cascades in skin cells, it has now surprisingly been determined that the growth of body and/or head hair can be substantially modified.
Briefly, the present invention features promoting the growth of body and/or head hair and/or combatting the loss of such hair via cyclooxygenase treatment, as well as, contrariwise, retarding and/or preventing the growth of body/cranial hair via lipoxygenase treatment.
More particularly according to the present invention, from a practical standpoint, eliciting one or the other enzymatic response can be carried out via several different techniques, more fully described below. Each such technique is bottomed on the same basic principle, namely, to supply the organism, in particular the skin cells thereof, with compounds intended either to inhibit or, to the contrary, to stimulate the action or influence of cyclooxygenase or lipoxygenase enzymes, the selection of which obviously being made depending on the particular pharmacological effect sought to be attained.
Thus, if it is desired to promote the growth and/or to limit the loss of body and/or head hair (or conversely, if it is desired to retard and/or to prevent the growth of such hair), and taking account of the fact that it is appropriate, in this instance, as indicated above, to favor the cyclooxygenase route (or, conversely, to favor the lipoxygenase route), it is then possible to adopt, as desired, at least one of the following techniques: either employing one or more lipoxygenase inhibitors (or, conversely, one or more cyclooxygenase inhibitors), or employing one or more cyclooxygenase stimulators or agonists (or, conversely, one or more lipoxygenase stimulators or agonists), or employing one or more lipoxygenase inhibitors (or, conversely, one or more cyclooxygenase inhibitors) in combination with one or more cyclooxygenase stimulators or agonists (or, conversely, one or more lipoxygenase stimulators or agonists), or, alternatively, employing one or more active agents having the property of being both lipoxygenase inhibitors (or, conversely, cyclooxygenase inhibitors) and cyclooxygenase stimulators or agonists (or, conversely, lipoxygenase stimulators or agonists) simultaneously.
Stated differently, it is thus possible to elicit a given enzymatic response by direct stimulation of one particular route and/or via inhibition of the xe2x80x9ccontraryxe2x80x9d route. The best results are typically attained by combining the two routes.
The present invention also features, both in a therapeutic regimen for promoting the growth of body and/or head hair and in a competing therapeutic regimen for limiting such hair growth, whether employing said inhibitors and stimulators or agonists of the aforesaid enzymatic routes, combining therewith treatment with at least one substrate which is directly metabolizable by lipoxygenases and cyclooxygenases and or with at least one precursor of said at least one substrate (synergistic or superadditive effect).
As utilized herein, by the term xe2x80x9csubstratexe2x80x9d suitable for lipoxygenase and cyclooxygenase is intended any substance which may be metabolized directly, as is in vivo, both by lipoxygenase enzymes and cyclooxygenase enzymes.
By the term lipoxygenase and cyclooxygenase substrate xe2x80x9cprecursorxe2x80x9d is intended any substance which may be metabolized in vivo by the organism into a suitable substrate for lipoxygenases and cyclooxygenases, as well as any substance inducing the formation of polyunsaturated fatty acids in living tissues (this may be determined by gas chromatography or by any other standard technique, such as those described by Pelick et al, P23 xe2x80x9cAnalysis of lipids and lipoproteinsxe2x80x9d, Perkin""s American Oil Chemist Society editions, Champaign, Ill., U.S.A.).
By the term lipoxygenase and cyclooxygenase xe2x80x9cinhibitorxe2x80x9d is intended any substance which makes it possible, in vivo, to limit or to inhibit totally the enzymatic activity of one or the other of the aforesaid enzymes.
By the term lipoxygenase and cyclooxygenase xe2x80x9cstimulatorxe2x80x9d or xe2x80x9cagonistxe2x80x9d is intended any substance which elicits, in vivo, an increase in the enzymatic activity of one or the other of these enzymes, the term xe2x80x9cagonistxe2x80x9d being included in the general designation xe2x80x9cstimulatorxe2x80x9d.
By xe2x80x9ctopical routexe2x80x9d is intended any conventional technique for administration of an active agent by direct application thereof to a superficial (or external) parts of the body, such as skin, hair, etc.
And by xe2x80x9csystemic routexe2x80x9d is intended any conventional technique for administration of an active agent into the circulation via a route other than the topical route, for example, via the oral and/or parenteral route.
Thus, in a first embodiment of the present invention, an in vivo regimen is provided for modifying the growth of body and/or head hair, such regimen comprising administering to a mammalian organism, notably a human being, via a topical and/or systemic route, at least one lipoxygenase or cyclooxygenase inhibitor, or at least one lipoxygenase or cyclooxygenase stimulator or agonist.
In the event that the subject regimen/treatment is more particularly intended to promote the growth and/or to limit the loss of body and/or head hair, at least one active agent comprising a lipoxygenase inhibitor and/or a cyclooxygenase stimulator is employed.
In the event that the subject regimen/treatment is more particularly intended to retard and/or prevent the growth of body and/or head hair, at least one active agent comprising a lipoxygenase stimulator and/or a cyclooxygenase inhibitor is employed.
In a particularly preferred embodiment of the therapeutic regimen according to the invention, conjointly with said inhibitors or stimulators, at least one substrate for lipoxygenases and cyclooxygenases, or a precursor of said at least one substrate, is also administered to the organism. Administration of said substrate or of said precursor may then be carried out via a topical and/or systemic route, in a simultaneous or separate manner, or alternatively, in fractions over time, each relative to the administration of the lipoxygenase and cyclooxygenase inhibitors or stimulators.
In another embodiment of the present invention, special packages containing several compartments, or xe2x80x9ckits,xe2x80x9d are used for carrying out the subject regimen, and in particular kits which comprise, in a first compartment, one or more lipoxygenase or cyclooxygenase inhibitors or one or more lipoxygenase or cyclooxygenase stimulators and, in a second compartment, one or more substrates for lipoxygenase and cyclooxygenase and/or one or more precursors of said one or more substrates. The compositions contained in said first and second compartments are thus considered combination compositions for simultaneous or separate use, or for use as separate fractions thereof over time, in a regimen for modulating the growth of body and/or head/cranial hair.
Thus, the present invention also features novel compositions or associations, per se, well suited for carrying out the various embodiments of the therapeutic regimen described above.
Next, the nature of the various active agents and compositions useful in the treatment of the present invention (inhibitor/stimulator/substrate/precursor) will be more fully described.
The inhibitory or stimulatory (or agonistic) activity of a given agent with respect to lipoxygenases or cyclooxygenases may easily be determined by one skilled in this art, in particular by means of the usual biochemical tests, generally based on chromatographic analyses. Thus, such activities may, for example, be determined via the following techniques or via any other standardized technique:
(a) Activity with respect to lipoxygenase 5, 12 and 15: exemplary is the technique comprising incubating a biological material (human polymorphonuclear leukocytes or hair) in the presence of C14 arachidonic acid or C14 linoleic acid; the hydroxy acids formed are extracted and separated by thin layer chromatography or HPLC chromatography (Vanderhoeck J. Y. and Bailey J. M. in J. Biol. Chem., 259, pp 6,752-6,761 (1984); Huang M. et al, Cancer Res., 51, pp 813-819 (1991); Baer A. N. and Green F. A. in J. Lipids Res., 34, pp 1,505-1,514 (1993); Ziboh V. A. et al in J. Invest. Dermatol., 83, pp 248-251 (1984);
(b) Activity with respect to lipoxygenase 5: exemplary are the spectrophotometric techniques described by Aharony D. and Stein R. L. in J. Biol. Chem., 261, pp 11,512-11,517 (1986), and by McMillan R. M. et al in Biochim. Biophys. Acta, 1005, pp 170-176 (1989);
(c) Activity with respect to cyclooxygenases: exemplary is the technique based on the use of a biological material (epidermis) incubated in the presence of C14 arachidonic acid; the hydroxy acids formed are extracted and separated by HPLC chromatography (Huang M. et al, Cancer Res., 51, pp 813-819 (1991) or identified by radioimmunoassays (Lysz T. W. and Needleman P. J., in Neurochim., 38, pp 1,111-1,117 (1982). Also exemplary is the test described in the article xe2x80x9cNitric Oxide Activates Cyclo-oxygenase Enzymesxe2x80x9d, by D. Salvameni et al, Proc. Natl. Sci. USA, Vol. 90, pp 7,240-7,244, August 1993.
The lipoxygenase inhibitors are advantageously selected from among the redox and non-redox inhibitors, redox inhibitor precursors, antioxidants, iron-chelating agents, imidazole-containing compounds, phenothiazines and benzopyran derivatives, as well as from certain eicosanoids.
The redox inhibitors may be selected from among catecholbutane derivatives (U.S. Pat. Nos. 5,008,294, 4,708,964 and 4,880,637, such as nordihydroguaiaretic acid (NDGA) or one of the enantiomers thereof, such as masoprocol.
The redox inhibitors may also be selected from among phenidone, lonapalene, indazolinones, naphazatrom, benzofuranol, alkylhydroxylamine and the compounds of the following formulae:
The non-redox inhibitors may be selected from among the hydroxythiazoles, methoxyalkylthiazoles, benzopyrans and derivatives thereof, methoxytetrahydropyran, boswellic acids and the acetyl derivatives thereof, and quinoline methoxyphenylacetic acids substituted with cycloalkyl radicals.
The antioxidant is advantageously selected from among the phenols, propyl gallate, flavonoids and natural compounds containing such flavonoids (Ginkgo biloba).
Exemplary flavonoids include the hydroxylated flavone derivatives such as flavonol, dihydroquercetin, luteolin, galangin and orobol. Also exemplary are the chalcone derivatives such as 4,2xe2x80x2,4xe2x80x2-trihydroxychalcone, ortho-aminophenols, N-hydroxyureas, benzofuranols and ebselen, and active agents that enhance the activity of the reducing selenoenzymes.
The iron-chelating agent is advantageously selected from among the hydroxamic acids and derivatives thereof, N-hydroxyureas, 2-benzyl-1-naphthol, catechols, hydroxylamines, carnosol, naphthol, sulfasalazine, zileuton, 5-hydroxyanthranilic acid and 4-(xcfx89-arylalkyl)phenylalkanoic acids.
The imidazole-containing compounds are preferably ketoconazole or itraconazole.
Exemplary eicosanoid inhibitors of lipoxygenases include octadecatetraenoic acid, eicosatetraenoic acid, docosapentenoic acid, eicosahexaenoic acid and docosahexaenoic acid and the various esters thereof, as well as various other eicosanoids, which may optionally be in ester form, such as PGE1 (prostaglandin E1), PGA2 (prostaglandin A2) viprostol, 15-monohydroxyeicosatetraenoic acid, 15-monohydroxyeicosatrienoic acid, 15-monohydroxy-eicosapentaenoic acid and leukotrienes B5, C5 and D5.
Various other compounds that inhibit lipoxygenases can also be used, for example active agents interfering with the flow of calcium, in particular phenothiazines and diphenylbutylamines, verapamil, fuscoside, curcumin, chlorogenic acid, caffeic acid, 5,8,11,14-eicosatetraynoic acid (ETYA), hydroyphenylretinamide, lanopalene, esculin, diethylcarbamazine, phenanthroline, baicalein, proxicromil, thioethers and in particular diallyl sulfide and di-(1-propenyl)sulfide.
The lipoxygenase stimulators themselves are advantageously selected from among the cytokines such as fibroblast growth factor (FGFxcex2), transforming growth factor (TGFxcex2) and epidermal growth factor (EGF).
The cyclooxygenase inhibitors are advantageously non-steroidal anti-inflammatory agents such as arylcarboxylic derivatives, pyrazole-containing derivatives, oxicam derivatives and nicotinic acid derivatives.
The cyclooxygenase stimulators or agonists are preferably selected from among the arachidonic acid metabolites, nitric oxide and nitric oxide-donating compounds, stanozolol, glutathione-donating compounds, neuropeptides and in particular vasoactive intestinal peptide (VIP), calcium, ionophores, anthocyanosides.
Lastly, an exemplary active agent which can serve as both a lipoxygenase inhibitor and as a cyclooxygenase stimulator is 6-chloro-2,3-dihydroxy-1,4-naphthoquinone (CDNQ).
With respect to suitable lipoxygenase and cyclooxygenase substrates, representative are the polyunsaturated fatty acids, in particular those containing 20 carbon atoms, such as arachidonic acid, dihomo-xcex3-linolenic acid, or, alternatively, eicosapentaenoic acid.
Particularly exemplary precursors of such substrates are the so-called essential polyunsaturated fatty acids such as linoleic acid, xcex1-linolenic acid and xcex3-linolenic acid, as well as cell membrane phospholipids such as phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and diphosphatidylglycerol.
The above substrates or substrate precursors, in particular, may be obtained from certain natural compounds, in particular from certain foods, of animal, vegetable or microbial origin (vegetable oil extracts such as common evening primrose oil, borage oil, black currant seed oil, evening primrose oil, fish oil extracts and insect tissue oil extracts).
According to the present invention, such natural compounds which contain the desired substrates and/or the precursors of the desired substrates can be used directly. It is also possible to use materials produced by industrial synthesis.
It will also be appreciated that mixtures of inhibitors, mixtures of stimulators, mixtures of substrates and mixtures of precursors, as well and mixtures of these mixtures can be used equally as well, provided, of course, that these mixtures of mixtures remain compatible with the desired therapeutic response.
The regimen or therapeutic treatment according to the invention will now be more fully described.
As indicated above, the subject treatment process essentially comprises administering to a mammalian organism, via the topical and/or systemic route, at least one lipoxygenase or cyclooxygenase inhibitor, or at least one lipoxygenase or cyclooxygenase stimulator. Such administration is preferably conducted in combination (simultaneous, separate or in separate fractions over time) with administration of at least one substrate, or at least one substrate precursor, as described above.
The enzyme inhibitors and stimulators are preferably administered topically.
The substrates and/or the precursors thereof may themselves be administered either via the systemic route, and in this event, preferably via the oral route, or, even more preferably, via the topical route.
In a particularly preferred embodiment of the present invention, topically acceptable compositions containing enzyme inhibitors and/or stimulators on the one hand, in conjunction with the substrates and/or the precursors thereof on the other, are applied to the skin and/or the scalp.
It will be appreciated that all of the above compounds and compositions may be conventionally packaged in a form suiting the mode of administration or application intended (lotions, shampoos, tablets, syrups and the like), and whether or not including any topically or systemically pharmaceutically acceptable carrier or diluent therefor.
The compositions or xe2x80x9ckitsxe2x80x9d according to the present invention include, in particular, the following:
(i) compositions (A) comprising at least one lipoxygenase inhibitor and at least one cyclooxygenase stimulator;
(ii) compositions (B) comprising at least one cyclooxygenase inhibitor and at least one lipoxygenase stimulator;
(iii) compositions (C) comprising at least one lipoxygenase inhibitor and/or at least one cyclooxygenase stimulator, in combination with at least one substrate for lipoxygenases and cyclooxygenases and/or at least one precursor of such a substrate;
(iv) compositions (D) comprising at least one cyclooxygenase inhibitor and/or at least one lipoxygenase stimulator, in combination with at least one substrate for lipoxygenases and cyclooxygenases and/or at least one precursor of such a substrate;
(v) xe2x80x9ckitsxe2x80x9d (E) comprising, in a first packet or compartment, at least one lipoxygenase inhibitor and, in a second packet or compartment, at least one cyclooxygenase stimulator;
(vi) xe2x80x9ckitsxe2x80x9d (F) comprising, in a first packet or compartment, at least one cyclooxygenase inhibitor and, in a second packet or compartment, at least one lipoxygenase stimulator;
(vii) xe2x80x9ckitsxe2x80x9d (G) comprising, in a first packet or compartment, at least one lipoxygenase inhibitor and/or at least one cyclooxygenase stimulator, or, conversely, at least one cyclooxygenase inhibitor and/or at least one lipoxygenase stimulator, and, in a second packet or compartment, at least one substrate for lipoxygenases and cyclooxygenases and/or at least one precursor of such a substrate.
Also as indicated above, each of the compositions (A), (B), (C) and (D), as well as each of the components in the compartments of the kits (E), (F) and (G), are conventionally packaged in a form suited for the various modes of administration or application envisaged therefor (lotions, shampoos, tablets, syrups, etc.). Thus, the compositions (A)-(D) and the kits (E)-(F) are preferably packaged in a form suitable for topical application and, in respect of the kits (G), the components of the first compartment are preferably packaged in a form adapted for topical application, whereas the components of the second compartment are packaged in a form adapted for oral administration.
In general, kits can be designed containing as many separate compartments as active agents (inhibitors, stimulators, substrates or substrate precursors) as desired or convenient to use.
The compositions or kits according to this invention, as well as the therapeutic regimen consistent therewith, may also include various conventional and usual additives and adjuvants, in particular cosmetics in the case of topical applications (in particular hair products), for example UV filters, thickening agents, penetrating agents such as urea, organic solvents such as ethanol and isopropanol, alkylene glycols, surface-active agents selected from among nonionic surfactants such as alkylpolyglycosides, cationic surfactants, anionic surfactants and amphoteric surfactants, dyes and pigments, anti-dandruff agents, perfumes and preservatives.
It is also possible to incorporate into the compositions according to the invention active agents having known activity in the field of body and/or head hair growth, for example such as 2,4-diamino-6-piperidinopyrimidine-3-oxide marketed under the trademark xe2x80x9cMinoxidilxe2x80x9d by Upjohn.
To attain appreciable effects, the frequency of administration or application of the compositions according to the invention, both with and without substrate or substrate precursor, is on the order of one to two times per day, for such prolonged period of time as is required to elicit the desired therapeutic response. In this regard, it should be appreciated that therapeutically effective amounts of inhibitors and or stimulators are, in general, quite low.
The present invention finds particularly useful applications in the field of treating various pathologies affecting the skin and/or the scalp, in particular hirsutism and alopecia, in particular iatrogenic alopecia.
In order to further illustrate the present invention and the advantages thereof, the following specific examples are given, it being understood that same are intended only as illustrative and in nowise limitative.
In said examples to follow, each reported composition was formulated and tested for its efficacy in modulating the growth of mammalian hair; also in said examples to follow, the term xe2x80x9cno-rinse lotionxe2x80x9d connotes a cranial hair formulation which need not be rinsed with water or the like after application thereof, while xe2x80x9crinse-lotionxe2x80x9d connotes that a subsequent rinse with water or the like is indeed carried out.


The powder injection system consists of a dosage chamber directly fed by a conventional powder feeder and communicated with barrel of the detonation gun through a direct conduit. In this way, the pressure wave advancing through barrel enters the communication conduit and upon reaching dosage chamber undergoes a sudden expansion, interrupting powder feeding from the continuous feeder and causing the full fluidization of powder contained in dosage chamber. The fluidized powder is suctioned to barrel where it remains until the pressure wave generated in a new detonation cycle carries it away, depositing it on the surface of the part to be coated.

This invention relates to the field of thermal spray technologies for applying coatings, and in particular to detonation thermal spray.
At this time, detonation spray technology is mainly used to apply coatings to workpieces exposed to severe wear, heat or corrosion and is fundamentally based on using the kinetic energy produced in the detonation of a combustible mixture of gases to deposit powdered coating materials on workpieces.
Coating materials typically used in detonation processes include powder forms of metals, metal-ceramics and ceramics and are applied to improve resistance to wear, erosion, corrosion, as thermal insulators and as electrical insulators or conductors.
Spraying by detonation is performed by spray guns which basically consist of a tubular detonation chamber, with one end closed and another open, to the latter being attached a tubular barrel. A combustion gas mixture is injected into the detonation chamber and ignition of the gas mixture is achieved with a spark plug, causing a detonation and consequently a shock or pressure wave which travels at supersonic speeds inside the chamber and then inside the barrel until it leaves through the open end of the barrel.
The coating material powder is generally injected into the barrel in front of the propagating shock wave front and is then carried out of the open end of the barrel and deposited onto a substrate or workpiece placed in front of the barrel. The impact of the coating powder onto the substrate produces a high-density coating with good adhesive characteristics.
This process is repeated cyclically until the part is adequately covered.
Powder feeders commercially available supply a continuous feeding which makes them adequate for high-velocity or plasma spray technologies. Since detonation is a discontinuous process, however, it requires discontinuous powder feeding.
Feeders used in detonation devices provide discontinuous feeding by using devices which control the amount of powder supplied to the detonation barrel in each explosion. These devices, however, are designed specifically for each type of gun, that is, they cannot be interchanged for use with other guns or in other machines which require feeding powder.
With respect to the powder measuring system employed. they can be classified in two categories:
a) Mechanical: These devices use moving mechanisms (valves, spindles, gears, etc.) to introduce constant quantities of powder in each detonation cycle. Devices of this type are described for example in U.S. Pat. NO. 3,109,680, and in European Patent 0 484 533.
These devices have the main advantage of providing precise measurements but are however of great complexity they have many components. Their reliability is low since they require periodic maintenance to maintain the precision of the measurement. Finally their productivity is low since they is are limited to low operation frequencies.
b) Pneumnatic: These devices use gas pulses synchronised with the detonation pulses to introduce the powder cyclically in the detonation barrel, with these pulses sometimes being obtained from the detonation process itself. The elegance and mechanical simplicity of these devices has contributed to their wide use despite their precision being questioned. There are also numerous Patent documents such as PCT/US96/20129 by the same authors.
These devices share the characteristic of incorporating a volume or deposit in which a limited amount of powder is stored, which, by gravity, feeds another volume or dosage chamber which feeds the detonation barrel by a gas impulse. The disadvantage of these systems is their lack of precision in the amount of powder dosed, mainly due to their difficulty, over long spray periods, of keeping stable the volume and/or pressure of the feeding deposit. This is due to the fact that part of the detonation wave enters the powder feeding deposit, pressurizing it so that the powder falls under gravity and due to the pressure existing in the deposit at each time.
In addition, since the amount of powder entering the dosage chamber cannot be perfectly controlled, the degree of fluidization produced by the impulse gas cannot be controlled either, and thus it is difficult to know precisely the amount of powder injected into the barrel.
Furthermore, since in these devices feeding from the deposit to the dosing chamber is by gravity, when the detonation gun generally handled by an industrial robot) assumes positions in which the powder deposit is not vertical, the powder will not fall into the dosage chamber continuously. Thus, it is difficult to ensure a constant feeding.
Document GB-A-2 192 815 is known in prior art, which describes a detonation coating device comprising a barrel open at one end, a gas feeding system, a blast initiating assembly and a powder bath metering unit consisting of a vertically oriented bunker changing at its lower part into a vertical tube under which, inside the barrel, a horizontal rack is located. The barrel is oriented vertically with its axis parallel to the axis of the bunker, whereas the tube is connected to the barrel through the closed butt-end of the latter.
In British Patent GB-2192815, the deposit containing the powder to be discharged is placed vertical, with the powder falling on the distribution tray under the action of gravity, which moans that the gun can only operate in positions where the deposit, the distribution duct and the tray are arranged vertically, as otherwise the powder would not be supplied. Thus, this gun cannot be used mounted on a robot arm as the latter""s motion would be limited by the position of the powder deposit.
The powder is fed from a closed deposit, so that as the deposit is emptied, conditions inside it change, particularly the temperature and pressure. Thus it is not possible to ensure a control of the amount of powder introduced.
The dosing of the powder to be used in each blast cycle is determined by size and arrangement of he distribution tray, and is interrupted when the powder reaches a height in the tray which obstructs the outlet of the distribution duct, so that the gas carries the amount of powder present in the tray. Thus, there is not an exact control of the dosed amount as the tray may be more or less filled depending on the chamber conditions and on the powder.
The powder feeder is on a fixed position on the rear wall of the combustion chamber, so that it is only suitable for performing certain types of coatings. This is so because, depending on the type of coating dust employed, a specific barrel length is required, and as the dust feeder is on the rear wall the length of the gun will always be the same. Thus, for coatings which require different barrel lengths we would need a different gun, suitable for this coating. The gun of GB-2192815 is therefore quite inflexible as regards the coatings which may be obtained.
This detonation coating device is not suitable for providing good coatings with any kind of materials, but it is only appropriate for particular coatings.
The present invention fully solves the above disadvantages by using an injection system which allows employing a conventional type continuous powder feeder for feeding a detonation spray system, the powder injection being performed cyclically, in synchronization with the gun spray frequency and with great precision in the powder dosage.
The system proposed allows directly connecting the gun and the continuous powder feeder and consists of a dosage chamber which receives the continuous powder feeding and a conduit which directly communicates the chamber with the gun barrel. Consequently, in each detonation cycle, the detonation pressure wave reaches the dosage chamber, momentarily interrupting the feeding so that the ensuing suction of the detonation wave carries the powder contained in the dosage chamber,thereby injecting it into the gun barrel.
With this object the dosage chamber communicates with the gun barrel by a direct tubular conduit of small diameter, so that the pressure wave that advances through the barrel passes to the communication conduit and on reaching the dosage chamber undergoes a sudden expansion which fills the chamber with pressurized gas, blocking the entry of the powder feeding conduit. In this way, the feeding of powder from the continuous feeder is cyclically interrupted, and it is therefore possible to determine the exact amount of powder present in the dosage chamber at the time of detonation.
The sudden expansion of the gas in the dosage chamber creates a turbulence which produces the fluidization of all the powder contained in the dosage chamber so that the suction process, which follows the detonation, carries all the powder contained in the chamber, so that it is possible to control the exact amount of powder injected into the barrel. In addition, as the pressure wave is composed of hot gases produced in the combustion process the interaction of these gases with the powder contained in the dosage chamber produces a preheating of the powder which favors its fluidization.
In this way, when the pressure wave generated in the detonation passes the communication conduit of the dosage chamber, the low pressure generated after the detonation wave creates a suction which carries the gas contained in the dosage chamber and the fluidized powder. The powder carried reaches the barrel, where it remains until the pressure wave generated in the following detonation cycle carries it, depositing it on the surface of the part to be coated.
With this injection system the pressure wave from the detonation is made to perform the injection of powder into the barrel cyclically and synchronized with the gun firing frequency, thus transforming a continuous powder feeding into a pulsed injection to the gun barrel without using complex mechanical devices.
In addition, the expansion created by the dosage chamber reduces the velocity of the pressure wave preventing it from eroding the dosage chamber and advancing into the powder feeder, eliminating the risk of it producing irreparable damages to the feeding system.
The dosage chamber presents an elongation or auxiliary chamber opposite the communication conduit to the detonation barrel which is meant to increase the length of the dosage chamber to reduce the force of the impact and therefore the effects of the erosion produced by the encounter of the gases and the powder in this area of the dosage chamber.
The device of the invention presents the following advantages:
It favors a cyclical interruption of the feeding by the detonation pressure wave.
It favors a preheating and fluidization of the powder by its interaction with the hot gases of the combustion.
It allows feeding a precise amount of powder in each explosion by the suction effect which follows the pressure wave in each detonation.

Powder injection system for detonation-operated projection gun


A machine that makes bubbles that are dispensed vertically. A membrane-forming system forms a bubble solution membrane over a bubble ring. Air is passed through the bubble ring by a blowing fan, which is intermittently operated to allow contact between a membrane-forming ring and the bubble ring. Bubble solution is continuously supplied to the bubble rings from a central reservoir. Safety switches prevent operation of the bubble-making machine unless there is bubble solution in the reservoir, the main housing is properly connected to the fan, and the bubble machine is in an upright position (and not tipped over). The present invention provides continuous operation for the duration of the bubble solution supply, and is easily washed, used, maintained, and manufactured.

1. Field of the Invention
This invention relates to bubble making and more particularly to a machine for making soap bubbles that are dispersed in a generally vertical manner.
2. Description of the Related Art
Bubbles made of a solution of water and soap or detergent are well known in the art, as are means by which bubbles can be produced.
Many people are familiar with the standard child""s toy of a bottle of bubble solution having a bubble wand inside. A screw top lid generally keeps the wand and solution closed in the bottle, and when the child or the person wants to blow bubbles, the lid is unscrewed, the wand is removed, and the person""s breath is blown through the ring, or loop, formed by the bubble wand. The bubble solution membrane adhering to the teeth of the toothed ring circumscribing the bubble wand is then stretched with the blowing breath and forms bubbles that fly away from the bubble wand. Generally, a membrane is formed across the bubble ring of the bubble wand when it is extracted from the bubble solution. If this is not so, bubbles do not form and the wand must be dipped again into the bubble solution. With practice, bubbles of several sizes may be blown from the bubble wand. The wand itself generally has a handle so that the ring may be dipped in the bubble solution without getting additional soap on the child""s fingers.
Other bubble making devices are generally variations on this theme where a vertically-disposed bubble ring is supplied with bubble solution, a serrated or toothed extension extends from the bubble ring to provide additional surface area, and the initial membrane formed across the bubble ring serves as the source for bubbles when air is blown through the ring. The bubbles are generally blown horizontally from a vertically-disposed bubble ring.
This is generally the basis for a variety of devices, including a pumpkin bubble blower, Item No. 35917 of the 2001 Johnson Smith catalog where a vertical ring of several such bubble rings is rotated through a reservoir of bubble solution. A squirrel cage or other type of fan then blows air through individual rings as they travel above the reservoir and past the fan. The limited amount of soap that each of the rings can hold is then exhausted and the ring is returned into the reservoir by circular rotation. The fan is then focused upon the next bubble ring and proceeds to blow bubbles from it.
U.S. Pat. No. 5,879,218 issued to Tao and assigned to Cap Toys, Inc. for a Bubble Apparatus and Method issued Mar. 9, 1999, has a bubble making apparatus for producing bubbles from a gun like device. Bubbles are expelled from one aperture while an additional air blowing aperture serves to disperse the bubbles away from the opening to the bubble aperture.
U.S. Pat. No. 4,764,141 issued to D""Andrade on Aug. 16, 1988, for a Toy Bubble Blowing Machine has a housing that may simulate a motor and may be mounted on a rideable toy such as a bicycle or automobile. A bubble wand with a plurality of wand heads share a central hub, and a Geneva mechanism is used to sequentially rotate each of the wand heads through bubble solution and forced air in sequence.
Other machines and devices are known in the art. Many of these blow bubbles in a horizontal, and not a vertical, direction. Blowing bubbles in a vertical direction is generally not possible with these systems, as the bubble heads must be rotated through a horizontal reservoir of bubble solution and consequently must be orthogonal, or at a right angle, to such bubble solution. Tilting the machine as a whole into an upright direction would generally spill the bubble solution out of the reservoir, thereby eliminating the source of bubble solution for future bubbles from the bubble machine.
Consequently, it would be an advance in the art to provide means by which bubbles could continuously be produced and blown vertically from an on-going bubble machine. Such a device would preferably be easy to use, easy to clean, and very reliable in that it would only function if properly assembled and would cease to function if tipped over.
The present invention as set forth herein solves many of the problems present in the prior art, as well as providing additional advantages and benefits that have heretofore not been seen.
The present invention provides a machine for making soap bubbles that are dispensed and dispersed in a generally vertical manner. This is in distinction to prior art devices, which generally dispense their bubbles in a horizontal fashion.
A fan is used to blow air upwardly through a housing, which is generally closed by two flaps when air is not blown by the fan. The flaps enjoy hinged attachment with the top of the housing and are generally flush with that top. The flaps are generally light in nature so that they may be forced open by the fan-blown air. The flaps generally fit within the inner perimeter of the housing end and each has membrane-forming rings at one end. These rings engage bubble-making rings that have circumscribing toothed rings acting as bubble stabilizers.
In order to initially form a membrane across the bubble ring, the membrane-forming rings come into contact with the bubble rings and the bubble solution held in a bubble ring channel associated with the bubble rings. When withdrawn from a bubble ring, the membrane-forming ring takes bubble solution with it causing a bubble solution membrane to form over the bubble ring. The membrane formed across the bubble ring is then subject to the air blown by the fan, which has sufficient force or pressure to blow bubbles from the bubble rings.
The flaps extend upwardly from the housing and direct the blown air and the bubbles away from the bubble-making machine. While the bubble rings are continuously supplied with bubble solution from a central reservoir, the membrane sometimes ruptures and the creation of bubbles ceases, even though there is bubble solution in the bubble ring channel and air is blowing from the fan. In order to continually create a membrane across the bubble rings, the fan is intermittently turned off so that the flaps may descend towards the housing and the membrane forming rings may engage the bubble solution in the bubble ring channel. The fan then starts to blow, lifting the flaps and the membrane-forming rings, forming a membrane across the bubble ring, and creates additional bubbles.
The housing may be connected to a fan framework by a bayonet connection, and four xe2x80x9cAAxe2x80x9d batteries may power an intermittent timing circuit to control the intermittent operation of the fan. A standard bubble solution container often purchased at toy stores and elsewhere is fitted with a special self-closing lid that fits over a float cage to allow flow of the bubble solution into the reservoir. Vacuum pressure, much in the same way as a water dispenser, keeps the bubble solution in the bottle. The presence of bubble solution in the reservoir causes a magnetic float to lift from the bottom of the reservoir. The floating of the magnetic float closes a switch in the intermittent circuit enabling the fan to turn on. Additional switches in the intermittent circuit allow coupling of the circuit to the housing so that the proper attachment of the housing to the fan""s framework is detected by the intermittent circuit. Finally, a tip-over switch is present in the intermittent circuit which when open (indicating a tip-over condition) ceases operation of the fan.
In this manner, a bubble machine dispensing bubbles in a vertical manner may be manufactured and produced in a cost-efficient, highly useful, and very efficient manner. Additionally, the enjoyment and/or merriment that can be elicited by the accompaniment of bubbles is better provided, and individuals or circumstances complemented by such activity are more easily achieved.
It is an object of the present invention to provide a bubble machine.
It is yet another object to provide a bubble machine that creates and dispenses bubbles in a vertical manner.
It is yet another object of the present invention to provide a bubble machine that can continually create bubbles, although a membrane is temporarily absent from a bubble ring.
It is yet another object of the present invention to provide a continual supply of bubble solution to bubble rings creating vertically-dispersed bubbles with reduced leakage.
It is yet another object of the present invention to create a bubble machine that is easily cleaned.
It is yet another object of the present invention to provide a bubble machine that requires little monitoring during operation.
These and other objects and advantages of the present invention will be apparent from a review of the following specification and accompanying drawings.


This invention is directed to methods for treating hyperhidrosis in mammals. Specifically, the methods of this invention involve the topical administration of glycopyrrolate compounds to humans.

1. Field of the Invention
This invention is directed to methods for treating hyperhidrosis in mammals. Specifically, the methods of this invention involve the topical administration of an effective amount of a glycopyrrolate compound to a mammal suffering from hyperhidrosis.
The following publications, patent applications and patents are cited in this application:
1. Riolo et al., South Med J. 83:1138-1143 (1990)
2. Glogau R. G. Cermatol. Surg. 24:817-94 (1998)
3. Schnider et al., Br. J. Dermatol. 136:548-52 (1997)
4. Atkin et al., xe2x80x9cTreatment of diabetic gustatory sweating with topical glycopyrrolate creamxe2x80x9d Diabetic Medicine 13:493-494 (1996)
5. Shaw et al., xe2x80x9cA randomized controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweatingxe2x80x9d Diabetologia 40:299-301 (1997)
6. May et al., xe2x80x9cFrey""s Syndrome: Treatment with topical glycopyrrolatexe2x80x9d Head and Neck (January/February 1989) p.85-89
7. Col. Leonard L. Hays, xe2x80x9cThe Frey syndrome: A review and double blind evaluation of the topical use of a new anticholinergic agentxe2x80x9d The Laryngoscope 88:1976 (1978)
8. Remington""s Pharmaceutical Sciences, Mace Publishing Company Philadelphia Pa. 17th ed. (1985)
9. U.S. Pat. No. 5,525,347, Kellner et al.
10. U.S. Pat. No. 2,956,062, Lunsford et al.
11. Hays et al., xe2x80x9cThe Frey syndrome: a simple, effective treatmentxe2x80x9d Otolaryngol Head Neck Surg. 90:419-425 (1982)
All of the above publications, patent applications and patents are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent was specifically and individually indicated to be incorporated by reference in its entirety.
2. State of the Art
Hyperhidrosis is an idiopathic pathological condition characterized by excessive, uncontrollable sweating beyond that required to cool the body. Disturbance of the central nervous system has been associated with this condition. It affects approximately one out of every one hundred people. Hyperhidrosis not only may result in intense social embarrassment, but also may even interfere with a person""s occupation.
It most often involves one or several areas, especially the hands, axillae, feet or face, although it can even involve the whole body. Palmar hyperhidrosis is the most common form. Antiperspirants are generally ineffective in treating this form of perspiration. Oral medications are occasionally beneficial, but may have side effects. As a result, many persons with hyperhidrosis have resorted to a surgical procedure, endoscopic thoracic sympathectomy (1). Although the surgery affords permanent benefit in some 40% to 90% of affected individuals, it is invasive, requires general anesthesia and is not without potential side effects. As many as 50% of persons who have undergone thoracic sympathectomy develop compensatory and annoying sweating of the trunk or thighs.
More recently, botulinum A neurotoxin (BOTOX) which blocks the action on sweat glands of acetylcholine that is released by the autonomic nerves, has proven effective in hyperhidrosis. Minute amounts of BOTOX injected into the palms or axillae of affected individuals results in statistically significant benefit (2,3). The effect lasts for several months but requires repeat injections.
A non-invasive, convenient and effective treatment with few side effects would be a welcome alternative for treating hyperhidrosis.
Topical glycopyrrolate has been used previously to treat gustatory sweating associated with diabetic autonomic neuropathy (4, 5) In this disorder, sweating that often is profuse, begins soon after the patient ingests food, starting on the forehead and then involving the face, scalp and neck. A solution of glycopyrrolate was applied to the face of the patient which prevented the gustatory sweating.
Similarly, glycopyrrolate has also been used previously to treat gustatory sweating associated with Frey""s syndrome which may develop after parotidectomy (11, 6, 7). Frey""s syndrome is believed to result from the aberrant reinnervation of the sweat glands of the face by the severed parotid parasympathetic nerve fibers.
In both diabetic gustatory sweating and Frey""s syndrome, the profuse facial sweating is induced by the specific stimulus of eating. Moreover, the sweating in each is a consequence of a distinct neuropathological process. In contrast, hyperhidrosis occurs spontaneously without a specific stimulus.
Glycopyrrolate administered with iontophoresis has been used to treat hyperhidrosis(8). In this case 0.1% of glycopyrrolate was administered topically to the skin and then the area of application was subjected to iontophoresis. For some patients, this treatment regime reduced the hyperhidrosis for up to 4 weeks. However, the patients needed to attend at the physicians office for the treatment and the treatment was associated with side effects such as abdominal discomfort and this treatment was not effective for all patients.
This invention is directed in part to the discovery that the daily topical application of a 0.25% to 6% glycopyrrolate compound to a mammal overcomes many of the prior problems in treating hyperhidrosis. Additionally, it provides advantages heretofore not achieved by conventional treatments for hyperhidrosis. For example, the glycopyrrolate compound to be applied does not have the side effects associated with Botox treatments or iontophoresis.
This invention is directed to methods for treating hyperhidrosis by the topical application of a composition comprising from about 0.25 to 6% by weight of a glycopyrrolate compound to a mammal.
This invention is directed to a method for alleviating hyperhidrosis in a mammal, which method comprises the steps of identifying a mammal susceptible to hyperhidrosis; and topically administering to the skin of said mammal a composition comprising from about 0.25% to 6% by weight of a glycopyrrolate compound. Preferably, the glycopyrrolate compound has formula I:
wherein Xxe2x88x92 is a pharmaceutically acceptable counter ion salt.
This invention is also directed to a method for alleviating hyperhidrosis in a mammal, which method comprises the steps of identifying a mammal susceptible to hyperhidrosis; and topically administering to said mammal a pharmaceutical composition comprising from about 0.25 to 6% by weight of a glycopyrrolate compound and a pharmaceutically acceptable excipient. Preferably the glycopyrrolate compound has formula I:
wherein Xxe2x88x92 is a pharmaceutically acceptable counter ion salt.
This invention is directed to methods for treating hyperhidrosis in a mammal by the topical application of a glycopyrrolate compound to a mammal.
Definitions
As used herein, the following terms have the following meanings;
The term xe2x80x9cglycopyrrolate compoundxe2x80x9d means a compound of the formula:
wherein Xxe2x88x92 is a pharmaceutically acceptable counter ion salt.
The term xe2x80x9cglycopyrrolate compoundxe2x80x9d also refers to analogues of glycopyrrolate capable of inhibiting hyperhidrosis wherein the chemical structure has been modified so as to introduce, modify and/or remove one or more functionalities of the structure. For example, such modification can result in the removal of an OH functionality, the introduction of an amine functionality, the introduction of a halo functionality, and the like. In so far as the glycopyrrolate analogues are capable of inhibiting hyperhidrosis they are encompassed by the definition of xe2x80x9cglycopyrrolate compoundxe2x80x9d.
Hyperhidrosis is a condition commonly known and understood by the average consumer who lacks any medical skill. It is an idiopathic condition characterized by excessive, uncontrollable perspiration beyond that required to cool the body.
The term xe2x80x9cmammalxe2x80x9d includes, without being limiting, such mammals as mice, rats, ovines, bovines and humans. Preferably the mammal is a human.
The term xe2x80x9ctherapeutically effective amountxe2x80x9d means that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by a researcher, veterinarian, medical doctor or their clinician. In particular, with regard to treating the disorders of hyperhidrosis, the xe2x80x9ctherapeutically effective amountxe2x80x9d is intended to mean that amount of the glycopyrrolate compound that will prevent or alleviate the hyperhidrosis.
The glycopyrrolate compound is effective over a wide dosage range and is generally administered in a therapeutically effective amount. Preferably the composition topically administered contains from 0.25% to 6% by weight and more preferably from 0.5% to 4% by weight of glycopyrrolate. It will be understood, however, that the amount of the glycopyrrolate actually administered may be determined by a physician in light of the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered and its relative activity, the age, weight, and response of the individual patient, the severity of the patient""s symptoms, and the like.
The compound is preferably administered topically. The daily dose of the compounds may vary depending on the medical condition of the patient, the skin status, and the age of the patient. Compounds of the present invention may be administered in a single daily dose, or the total daily dose may be administered in divided doses of two, three or four times daily. The compound may be applied to the hands, face, scalp, neck, trunk, back, limbs, axillae and/or groin of the human. Preferably, the glycopyrrolate compound is applied to the hands, face, neck, axillae or scalp of the human. Preferably, the glycopyrrolate is administered without the simultaneous or subsequent administration of iontophoresis to the skin.
Patients susceptible to hyperhidrosis include, but are not limited to, patients exhibiting idiopathic post stroke, central nervous system disease or injury resulting in hyperhidrosis.
The term xe2x80x9cpharmaceutically acceptable counter saltxe2x80x9d refers to salts which retain the biological effectiveness and properties of the glycopyrrolate compounds of this invention, which are not biologically or otherwise undesirable, and which carry an anionic charge. The glycopyrrolate compounds of this invention form salts by virtue of the presence of the quarternary ammonium thereon.
Pharmaceutically acceptable counter salts may be prepared from inorganic and organic acids. Salts derived from inorganic acids include hydrochloric acid, hydrobromic acid, hydrogen fluoride, hydrogen iodide, sulfuric acid, nitric acid, phosphoric acid, and the like. Salts derived from organic acids include acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluene-sulfonic acid, salicylic acid, and the like.
The compounds of the present invention may be administered in a pharmaceutical composition comprising the active compound in combination with a pharmaceutically acceptable carrier adapted for topical administration. Topical pharmaceutical compositions may be in the form of a solution, cream, ointment, mousse, gel, lotion, powder or aerosol formulation adapted for application to the skin. These topical pharmaceutical compositions containing the compounds of the present invention ordinarily include from about 0.25% to 6.0% by weight of the active compound, more preferably from about 0.5% to 4% by weight of the active compound, in admixture with a pharmaceutically acceptable excipient.
xe2x80x9cPharmaceutically acceptable excipientsxe2x80x9d refers to compositions which retain the biological effectiveness and properties of the glycopyrrolate compounds of this invention and which are not biologically or otherwise undesirable.
Topical preparation containing the active compound can be admixed with a variety of carrier materials or pharmaceutically acceptable excipients well known in the art. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of powders, suspensions, emulsions, solutions, syrups, alcoholic solutions, ointments, topical cleansers, cleansing creams, skin gels, skin lotions, mousses, roll-ons, aerosol or non-aerosol sprays in cream or gel formulations and soft gelatin capsules.
The compounds of the present invention may be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine or phosphatidylcholines.
In preparing a formulation, it may be necessary to mill the active compound to provide the appropriate particle size prior to combining with the other ingredients. If the active compound is substantially insoluble, it ordinarily is milled to a particle size of less than 200 mesh. If the active compound is substantially water soluble, the particle size is normally adjusted by milling to provide a substantially uniform distribution in the formulation, e.g. about 40 mesh.
Some examples of suitable excipients include alcohols, aloe vera gel, allantoin, glycerin, vitamin A and E oils, mineral oil, PPG2, myristyl propionate lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, sterile water, syrup, and methyl cellulose. The formulations can additionally include: lubricating agents such as talc, magnesium stearate, and mineral oil; wetting agents; emulsifying and suspending agents; preserving agents such as methyl- and propylhydroxy-benzoates; sweetening agents; and flavoring agents. The compositions of the invention can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures known in the art.
The glycopyrrolate composition may additionally contain one or more optional additives such as colorants, perfumes, etc. In practice, each of these optional additives should be both miscible and compatible with the glycopyrrolate compound. Compatible additives are those that do not prevent the use of the glycopyrrolate compound in the manner described herein.
Other suitable formulations for use in the present invention can be found in Remington""s Pharmaceutical Sciences(8).
Methods
The methods of this invention comprise the topical application of a composition comprising 0.25% to 6% by weight of a glycopyrrolate compound to the skin surface of a mammal, which glycopyrrolate compound acts to inhibit hyperhidrosis.
The skin surface is preferably dried, and then a glycopyrrolate compound is applied to the skin surface of the human at the desired site. The compound can be applied to the hands, face, scalp, neck, trunk, back, limbs, axillae and/or groin of the human.
Sufficient amounts of the composition are employed to cover (i.e., coat) the entire skin surface with a layer of the glycopyrrolate compound. If necessary, excess glycopyrrolate compound can be removed from the skin with a wipe or tissue paper.
After application, the glycopyrrolate compound penetrates the skin very slowly and has been associated with few side effects (11,4,5). The glycopyrrolate is allowed to dry. Cosmetics can be applied over the glycopyrrolate.
Compositions
Glycopyrrolate is readily commercially available. Glycopyrrolate can be made as follows. xcex1-phenylcyclopentaneglycolic acid is esterified by refluxing with methanol in the presence of hydrochloric acid and the resulting ester is transesterified with 1-methyl-3-pyrrolidinol using sodium as a catalyst. The transester is then reacted with methyl bromide to give glycopyrrolate (9,10).
Utility
It has been found that the application of glycopyrrolate to the skin of mammals suffering from hyperhidrosis reduces the unwanted perspiration at the location where the glycopyrrolate is applied.

Method for treating hyperhidrosis in mammals