The cutter bar of a header including two sickle bars is driven by a center drive system including a rotary input drive member driven by a motor, first and second rotary members each driven by the drive member about a generally upstanding first rotational axis. Each of the rotary members has an eccentric drive system for driving a respective sickle bar. A flywheel is driven by the rotary input drive member for common rotation therewith and the first and second rotary members are driven by a common drive sprocket to rotate in the same direction about the first and second rotary axes.

Sickle knives include a plurality of knife or sickle sections which are mounted in side by side relation forming an elongate metal knife assembly. The elongate knife assembly is normally supported so as to slide longitudinally along an elongate stationary bar that has forwardly projecting, spaced apart guards bolted to a structural beam. The knife assembly moves back and forth in a reciprocating movement to move the knives relative to the guards so that the leading knife edges of the knives cross over the guards or through slots in the guards.
In a harvesting machine the knife assembly extends along a forward edge portion of the header which can include conveying apparatus, such as one or more augers or drapers for conveying the cut plant material and crops to a feeder inlet of a combine or windrow forming apparatus of a windrower.
The knife assembly is driven in reciprocation longitudinally by an oscillating drive. Such drives are in some cases located at the sides of the header, so as to drive the knife assembly from the end. Additionally, for headers utilizing two drives located on opposite sides of the header, it is usually desired to time the operation of the drives such that the forces and vibrations generated by the respective drives cancel one another. This typically involves relatively long mechanical drive lines connecting the two drives together, which is disadvantageous as it adds weight, cost and complexity.
The knife assembly typically must accelerate and decelerate two times per cycle as a result of the reciprocating movement. A typical speed for the knife assembly is up to about 16 cycles per second. Thus, it can be seen, the reciprocating motion at a high cycle per second generates high acceleration values and high deceleration values that in turn generate high forces on the structural components. These high forces can have at least two negative effects, vibration at the drive system that may be transmitted to other components of the machine, and fatigue failure of the structural components themselves. On larger headers, for instance, headers 30 or 40 feet wide and greater, two knife assemblies each equal to one-half the extent of the header are often used.
Driving a knife assembly or assemblies of a header from a central location at the center of the header as is well known can provide several advantages compared to a side location. Notably among these advantages, the header structure is not required to support heavy drive units on both sides, such that the structure of the header can be lighter. Long timing apparatus extending between the ends can also be eliminated. If the drive mechanism is incorporated into a location that does not interrupt or require dividing crop or plant material flow through the crop flow area of the header, the normal crop flow of the header is not significantly impacted. And, since the drives are not located in the ends, the end dividers can be made significantly narrower, such that the header can have a shorter overall width, can be more easily maneuverable in relation to adjacent standing crop, and danger of downing the adjacent standing crop is reduced.
However it is necessary that such a structure is structurally sound in order to accommodate the high loads necessary and also that the structure does not interfere with the smooth flow of the crop over the drive and into the conveying system, whether this is an auger on a table or a draper system.


A ratchet assembly for a medical instrument having a handle and a trigger member for operating the medical instrument, the trigger member being movable relative to the handle between a first position and a second position and being biased by a biasing member toward the first position, the ratchet assembly comprising a rack disposed in the handle, an engagement member for engaging the rack, slidably disposed in the handle relative to the rack and connected to the trigger member so that displacement of the trigger member slides the engagement member relative to the rack, the engagement member being biased into engagement with the rack so that, as the trigger is displaced from the first position to the second position, the engagement member engages the rack in a plurality of positions so as to hold the trigger member at a desired point between the first position and the second position against the biasing member, and a cam member, arranged in the handle, for disengaging the engagement member from the rack when the trigger member is displaced to the second position, and for reengaging the engagement member with the rack when the trigger member is returned to the first position from the second position.

The invention relates to medical instruments and, particularly, to a ratchet assembly for such a medical instrument, especially for a surgical stapler.
Numerous medical instruments exist which are operated by a trigger or switch member or the like which pivots or slides relative to a handle of the instrument. Such operation of the trigger member typically operates the instrument for its intended function.
Typically, it is desirable to perform the pivot or movement of the trigger member and, thus, the operation of the instrument, in a step wise manner. It is desirable to provide such an instrument wherein such stepwise operation is facilitated.
It is further desirable to provide such an instrument wherein the trigger member readily returns to its initial position relative to the handle after the trigger member has been fully depressed, pivoted, or otherwise actuated so as to prepare for the next operation of the instrument.
It is thus the principal object of the invention to provide a ratchet assembly for a medical instrument which provides a smooth and reliable ratcheting or stepwise operation of the trigger member relative to the handle of the device.
It is a further object of the invention to provide such an assembly wherein the increment from step to step of the ratchet operation is small so as to provide small incremental steps and thereby accurate operation of the instrument.
A still further object of the invention is to provide such an apparatus wherein the trigger member is readily returned to the initial position after reaching a fully operated position.
Other objects and advantages will appear hereinbelow.


The present invention provides a hydrophilized cellulose fiber producing method, comprising oxidizing cellulose fibers in a reaction solution containing a N-oxyl compound, an oxidizing agent, and a co-catalyst and oxidizing other cellulose fibers using the reaction solution again. The present invention relates to a hydrophilized cellulose fiber producing method, comprising the steps of: (1a) oxidizing cellulose fibers in a reaction solution containing a N-oxyl compound, an oxidizing agent, and sodium sulfate to provide oxidized cellulose fibers; and (1b) separating the obtained oxidized cellulose fibers from the reaction solution, and then adding other additional cellulose fibers and oxidizing agent to the reaction solution to oxidize the cellulose fibers again to provide oxidized cellulose fibers.

Cotton garments (cellulose fiber products) such as underwear have been required to have high moisture-absorption properties and high moisture-desorption properties. Such a cotton garment (cellulose fiber product) with high moisture-absorption properties and high moisture-desorption properties may be obtained by, for example, hydrophilizing cellulose fibers used as raw materials. Various methods for hydrophilizing cellulose fibers are known, and one representative example of such methods is oxidizing a hydroxy group in cellulose to a carboxy group.
A known method of oxidizing a hydroxy group in cellulose to a carboxy group is oxidizing cellulose fibers used as raw materials in a reaction solution containing a N-oxyl compound such as 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and a halogen-based oxidizing agent in the presence of a co-catalyst (see Patent Literature 1, for example).
For industrial oxidation and hydrophilization of cellulose fibers, it is desirable to reuse the reaction solution for the oxidation treatment. However, if a reaction solution is reused in oxidation of cellulose fibers with a N-oxyl compound and a halogen-based oxidizing agent, a halogen-based salt, which is a by-product of the reaction, inhibits the reaction. Thus, with a used reaction solution, it is typically difficult to introduce carboxy groups to cellulose fibers with sufficient efficiency.

Method for producing hydrophilic cellulose fiber


Re-orientation of inlet ports to a by-pass valve which is used in industrial gas process systems to control the gas stream during system start-up, significantly reduces solid particle erosion of by-pass valve components and reduces costly system downtime for maintenance of by-pass valves.

This invention relates to a valve for use in industrial gas process sYstems, and, in particular, to a main steam stop valve by-pass valve for steam turbine applications.
In the operation of steam turbines in commercial power plants, stop valve by-pass valves (SVBV) play an important role in turbine start-up. During start-up, the gas stream is throttled and controlled at the SVBV only. As a result, start-up and initial loading of the steam turbine may be accomplished with all control valves wide open, resulting in uniform steam flow and warming to all turbine shell passages. The SVBV itself is typically mounted inside a larger master valve assembly, such as a stop valve assembly, wherein the SVBV functions as the valve disc. For purposes of illustration, the discussion which follows will focus on the use of an SVBV in a stop valve assembly. The SVBV performs its by-pass function when the stop valve is closed. Thus, the SVBV, as its name implies, functions as a valve within a valve.
Typically, an SVBV is comprised of a number of components, the largest of which is the stop valve disc. The master valve disc is that part of the SVBV which seats in the stop valve assembly, and includes the outlet ports of the SVBV. Inside the SVBV, a by-pass disc is mounted on a stem which is slidably inserted in the center of the master valve disc, and functions to open or close the SVBV. A valve cap with inlet ports is mounted on the top of the stop valve disc. When the by-pass disc is moved down to seat in a first position in the stop valve disc, the steam flow is restricted or stopped. As the by-pass disc is moved upward, an annulus is created between the by-pass disc and the stop valve disc and steam flows through the SVBV. At a point maximum upward travel, the by-pass disc seats in a second position in the valve cap, and the steam annulus within the stop valve disc is wide open to the inlet and outlet ports. Thus, steam or gas flows freely through the inlet ports and annulus to the outlet ports in the stop valve disc. U.S. Pat. No. 3,013,767 is typical of such components present in prior art valve assemblies.
Problems arise in the operation of steam turbines, as in the operation of other industrial gas process systems, when solid particles carried by the gas stream impinge upon and erode pipes, valves and other process equipment. In particular, steam carries microscopic oxide particles that spall from high temperature boiler tubes, steam headers, and steam piping. High velocity flow and changes of direction cause the particles to impact on stationary nozzles, rotating blades, and valve surfaces, causing erosion. The rate of solid particle erosion is dependent in part on the size, velocity and angle of impact of solid particles, and on the number and duration of turbine start-ups. The central role of the SVBV in turbine start-up subjects the by-pass disc to significant erosion, requiring its replacement at regular intervals to avoid disc failure and forced outages. Solid particle erosion is a long-standing, industry-wide problem with significant economic impact upon operation and maintenance costs, as well as availability and performance, of the nation's power plants.
Thus, reduction or elimination of solid particle erosion of SVBVs in steam turbine applications, as well as in similarly demanding industrial gas process environments, is desirable to decrease operation and maintenance costs and improve system performance.


A system is disclosed for displaying information pertaining to the usage of Web pages. The system comprises first and second Web sites. The first Web site comprises plural Web-component files, each having a name in a Web-site directory. The second Web site comprises plural statistics files, each containing usage information about a corresponding Web-component file or sub-directory of Web-component files. The system further comprises a computing device that has a display screen, is operable by a user, and is in communication with the first and second Web sites. The computing device is operated under the control of Web-browser software effective for displaying, on the screen, Web components of the respective Web sites. Significantly, the computing device is effective for requesting and retrieving, from either of the Web sites, data that correspond to user-designated Web components, and it is effective for directing a data request to either of the Web sites in response to user-designation of a Web component from the other Web site.

The World Wide Web is currently a subject of intense and rapidly growing interest.
The World Wide Web is composed of interconnected data sources that are accessible to computer users through data-communication networks such as the Internet. The data available on the World Wide Web have been assembled by private individuals, commercial companies, government agencies, and special interest organizations. Much of this assembled information is organized into Web pages. A Web site is a collection of Web pages (and possibly other data which, together with Web pages, are generically referred to as Web components) offered by a sponsoring entity, herein referred to as the site owner.
Large Web sites are typically organized hierarchically. For example, corporate Web sites often consist of smaller Web sites, each providing information about a business unit of the parent company.
The Web site itself resides on one or more server hosts. Web components stored on the server host are offered to users of the World Wide Web through a software program known as a Web server. A network user downloads data from a Web site through a browser, a software program running on the client host. The browser establishes contact with the Web server and issues a request for data stored on the server host. This results in data from the server host being downloaded into the browser. This data is typically a HyperText document specifying information required by the browser to display the Web page (i.e., formatting information specifying the structure of the page, or URLs of images that are to be placed on the page), embedded client software programs which run inside the browser (e.g., Java bytecode), and other content to be downloaded to the client computer or displayable through client software programs that add to the browser's functionality (sometimes referred to as "browser plug-ins").
A visit to a Web site is defined as a series of downloads, from a specified Web server by a fixed client browser, that are contiguous in time. Each request for a Web component made by a client browser during the course of a visit is referrred to as a hit. (In at least some cases, it may be useful for distinguishing separate visits to consider the dormancy period between successive hits by a given client browser. A dormancy period exceeding a threshold of, e.g., fifteen minutes, may be taken to indicate the end of a visit.)
Commercial Web servers have the option of recording client requests in a logfile, generating a separate entry for each hit. In many cases, the logfile resides (at least temporarily) on the server host. The information collected in this file can include the hostname or host address of the visiting client, the time of the hit, and the name of the requested data file. An illustrative record of a client request is given below:
147.atlanta-02.ga.dial-access.att.net hostname -- userid and authentication (not shown here) [30/Nov/1997:00:03:09-0500] date and time GET request method /work/work.html name of page requested HTTP/1.0 protocol used 200 return code 9391 number of bytes transferred http://biz.yahoo.com/lucent.html referral page Mozilla/2.02E (Macintosh; U; 68K) agent used (browser)
From a visitor's point of view, it is clear that a visit to a given Web site begins with an initial request to the Web server (the entry point), consists of a number of consecutive downloads, and ends when the visitor either: (i) begins to request pages from a different Web site, or (ii) stops browsing altogether. The visitor's final request is referred to as the exit point.
The server host, on the other hand, experiences hits from many users simultaneously, and it records all requests chronologically. Consequently, the server host mixes visit information from different clients in the logfile. Because of this, it is not immediately evident, from an examination of the raw logfile, which hits correspond to which visit. Even the length of a given visit is not immediately evident. The lack of this information prevents the compilation of higher-level summaries of usage patterns.
Some software tools are commercially available for summarizing and displaying data describing Web-site usage Often, these packages require the running of a special client software program in order to view the usage data.
One drawback of such a tool is that only those users who have installed the client software will have access to the Web site's usage information, even though many geographically separated people may have a legitimate interest in this information. This group may include, e.g., content providers, Web designers, and even visitors.
A second drawback is that such a specialized client approach can become impractical because of the cost to install and maintain the client program for each interested party.
A third drawback is that the presentation of the reported information is divorced from the immediate context of the Web site itself. Thus, although it may be convenient for the user to move quickly from a statistic about some Web page to the page itself, it is much less convenient for the user to move from any desired page or a feature of such a page to a corresponding statistic.
Other software tools provide reports, in the form of HyperText documents, on the usage of selected (such as the most popular) pages. Information from these reports can be displayed via the user-side browser, and links are provided for viewing the selected Web pages. However, these software tools also fail to provide convenient access from a Web page to the statistics that pertain to it.

Method for characterizing and visualizing patterns of usage of a web site by network users


An electronic control system is provided to measure chassis twist from the front of the chassis to the rear of the chassis, determine the extent and direction of twist, resolve the data to eliminate the twist without inducing further stress to the chassis and secondarily, level the chassis with respect to earth after the torsion or twist of the chassis has been eliminated to achieve a planar condition. The system comprises two, two-axis tilt measurement sensors, a host control for data collection and system operation, a remote mounted diagnostics port, a user interface for the owner, operator or driver to initiate system operation and display of vehicle movement during the planarization process, with an external interface to pneumatic, hydraulic or electromechanical systems used to raise and lower each corner of the vehicle.

Recreational vehicles have become a very popular way of traveling, especially for extended periods of time. These vehicles are equipped with a wide variety of amenities that are normally found in a residence. These include fully appointed kitchens, complete bathrooms, laundry facilities, and entertainment centers. For many years, trailers have incorporated expandable rooms, sometimes called slide-outs, to increase the interior space while parked and yet maintain legal size requirements while in motion. In the past decade, expandable rooms have become very common in motorhome applications. Owners continue to want more space and more luxurious amenities. In recent years, consumer demands have resulted in manufacturers adding multiple slide-outs to their production models, sometimes as many as four or five in a forty or forty-five foot model. The next generation motorhome, travel trailer and fifth wheel will replace the multiple slide-out modules with one or two large slide-out modules. As these modules get longer, up to 30 ft in length or more, which will replace multiple slide-outs of length that range from 8 to 12 ft, care must be taken to eliminate the twist or torsion in the chassis. In normal operation of an RV, when the vehicle is parked on an uneven surface whereby one wheel at any of the four corners of the chassis rests in a position or plane that is higher or lower than the plane defined by the point of rest of the wheels on the other three corners of the chassis, the overall chassis will then be twisted, or in engineering terms, in torsion. This twist will distort the chassis and the RV structure that is attached. This distortion will make it impossible to extend and retract the above mentioned slide-out modules with ease and reliability. A large slide-out module that is extended to enjoy the larger living space becomes a liability if the module will not retract due to the distorted or twisted chassis, which makes retraction of the slide-out module impossible. If the slide-out cannot be retracted, the RV cannot be moved, a very serious inconvenience.
The present invention, uses two (2), two-axis sensors to measure the orientation of the vehicle chassis across the width of the chassis in addition to measurements taken along the longitudinal, fore to aft axis of the chassis. Each two-axis sensor is located at opposite ends of the trailer or motorhome chassis.
The present invention is a solid state control system that may be used on any type of vehicle to insure that the chassis of the vehicle is level, or perpendicular to the pull of gravity, and in a single plane without twist or distortion. Planarization is the process of insuring that a vehicle, material or entity is in this non-distorted, planar condition.
The components of the control system include the host computer or microprocessor, the front, two-axis sensor, the rear, two-axis sensor, the user""s control panel and a remote diagnostics port for System maintenance. Each of the front and rear sensor modules includes an electronic sensor to measure level in the X direction, the measurement taken across the width of the vehicle or chassis and the Y direction, the length of the vehicle. The first priority of the host computer is to compare the X direction readings at the front and rear of the chassis. Analysis of these data will determine the amount and direction of twist in the chassis. When the magnitude and direction of twist is determined, the host computer will resolve or eliminate the twist by raising or lowering opposite corners of the chassis. When planarization is achieved, the control will then lift either side and/or either end of the chassis to achieve a level condition. The lifting means will be inflation or deflation of the airbags that are used in the vehicle""s suspension system or raising and lowering of hydraulic or electromechanical jacks located at each of the four (4) corners of the vehicle.
In addition to the host computer and the front and rear sensors, a control panel or user interface is provided for the vehicle operator. The user interface provides a pushbutton for the driver/operator to initiate the leveling sequence. In addition, a multi-line/multi character display panel or multi-color LED""s may be provide to indicate which corner of the vehicle is high or low and allows the operator to observe the System in operation. The same panel will indicate to the owner/driver/user that the vehicle is planar and conditions have been met for proper operation of the slide-out modules.

Automated control system for vehicle leveling and elimination of torsion in a vehicle chassis


A downhole optic fiber wet-connect system includes first and second matable portions of a tool body; first and second matable portions of a connector. Further included is a first magnet associated with one of the first and second matable portions and a second magnet associated with the other of the first and second matable portions, the first and second magnets being oriented to attract one another; a first opening in one of the first and second matable portions of the tool body; a second opening in the other of the first and second matable portions of the tool body; and at least one of the first and second openings in the first and second matable portions of the tool body configured and dimensioned to loosely receive one of the first and second matable portions of the connector therein and a method for wet-connecting an optic fiber in a downhole environment.

In the hydrocarbon exploration and recovery arts it is increasingly common to see monitoring and/or control type devices in the downhole environment that require signal bearing connections to remote controllers, including surface controllers. Because downhole systems are generally built in pieces this necessitates the connection of signal conveying conduits while in the downhole environment, which often will be a dirty and wet environment. Dirty, wet environments in which connectors are intended to both mate and function, makes for challenges with respect to the connectors themselves. Careful consideration is necessary to prepare proper connections. In addition, since connections are often made several miles distant from the well operator, consideration with respect to alignment and mechanical forces is necessary. Because of these issues the types of connections that can be made in the downhole environment have been relatively limited and generally are costly to produce.

Downhole optic fiber wet connect system and method


The present invention is a method and system for executing whole domain searches based on user queries and producing a result list of root nodes. The method and system comprise searching a network containing a plurality of web sites further containing a plurality of pages by examining all pages of a web site and comparing indexed terms to desired search terms. A result list of domain root nodes is returned wherein not all search terms may appear on a single document or associated page of the root page. Pages containing desired search terms may be indexed and mapped to root nodes for access from a result list.

The Internet is a widely popular information retrieval mechanism for people with access to a communications network. Because a tremendous amount of information is available on the Internet, users often utilize search engines to locate information. Initiation of a search may generally require utilization of a search engine such as GOOGLE®, LYCOS®, YAHOO® or the like. These search tools build results from a user query, and return results in the form of a hyperlinked list of uniform resource locators (URLs) containing the requested terms. Specifically, text entered into a search field is compared against a repository of indexed words and pointers to an originating document. Search terms are matched against words and phrases on individual web pages, and a list of web pages is returned. Referring to FIG. 1, an exemplary list 100 of web pages provided by search engines known to the art is shown.
A majority of text searching algorithms is based on analyzing the content of individual documents. Conventional text searching algorithms only evaluate each document individually in a type of competition to see which documents match search criteria. When a user asks a query, he/she is looking for a small set of documents that provide an answer. Text queries tend to provide large answer sets and a one-size-fits-all relevancy ranking. These text searching algorithms typically include extracting words or phrases, creating indexing structures, and determining discriminators for calculating relevance. When a user submits a text query, the index identifies candidate documents or web pages and a resulting list is returned to the user.
Search technology has developed to provide more control regarding the appearance of a phrase or series of words on a page. For example, words must be in a specific order, words must appear near each other, or phrases cannot include certain words. The limitation on this technology, however, is that specific word combinations must appear on a single web page and not generally within an entire web site. Typically, search systems return results in the form of individual pages with corresponding URLs. These individual pages are sub-pages, or associated with a root page of a web site. Each URL must contain query terms and parameters as specified by a user. For example, a user may enter the query "X and Y" into a search system prompt. A search tool compares the query to a database, and a list of pages matching the criteria "X and Y" is returned. If "X" and "Y" are not located on the same page of a web site, the web page will not be included in the result list. Therefore, conventional search systems fail to return web sites that may contain the requested information but do not have all search terms located on a single page of the site. Therefore, a user may be prohibited from receiving possible relevant information.
Consequently, a need exists for a system and method for query based searches that provide results wherein at least one of the query terms or parameters may appear on a different page of a web site or domain.

System and method for searching internet domains

International Business Machines Corporation


Devices and methods for generating an alert for a vending machine are disclosed. A method of generating an alert includes monitoring a bus for at least one communication from the vending machine controller via the bus. The bus is then monitored for a response to the communication from a peripheral device to the vending machine controller via the bus. The response from the peripheral device is then processed. An alert is then generated based on the processed response. A peripheral device for generating the alert includes a bus interface configured to receive data from the bus and to transmit data onto the bus, and a processing unit coupled to the bus interface, the processing unit configured to process data received from the at least one other peripheral device and generate an alert based on the processed data.

Vending machines are often used to vend items and/or services to consumers in locations where it would be impractical or inefficient to staff human beings to provide the items/services. Because vending machines are typically located where the vendor cannot constantly monitor their operations, vendors rely on operation information stored by the vending machines in the vending machines' memory, such as diagnostic information for peripheral devices (e.g., coin acceptors/changers and bill validators/acceptors). A Digital Exchange ("DEX") interface is the current industry standard for gathering stored information by a vending machine.

Devices and methods for providing cashless payment and diagnostics for vending machines


A method of handling simultaneous communications comprises a first base station configuring a radio resource control (RRC) connection to a communication device; the first base station configuring a second base station as a secondary base station to the communication device; the second base station configuring a signalling radio bearer (SRB) to the communication device via the first base station; the second base station transmitting a second measurement configuration to the communication device; the second base station receiving a second measurement report corresponding to the second measurement configuration via the SRB from the communication device; and the second base station adding a secondary cell (SCell) of the second base station to the communication device, releasing a SCell of the communication device, or changing a primary secondary cell (PSCell) of the communication device via the first base station or via the SRB.

1. Field of the Invention
The present invention relates to a method and communication device used in a wireless communication system, and more particularly, to a method and communication device of handling simultaneous communications.
2. Description of the Prior Art
A long-term evolution advanced (LTE-A) system, as its name implies, is an evolution of the LTE system. The LTE-A system includes advanced techniques, such as carrier aggregation (CA), dual connectivity, etc. A user equipment (UE) receives/transmits packets from/to two evolved Node-Bs (eNBs), when the UE is configured to dually connect to the two eNBs in the dual connectivity. One of the two eNBs is a master eNB (MeNB) of the UE and the other is a secondary eNB (SeNB) of the UE in the dual connectivity.
Currently, mobility management and radio resource management for the UE are only performed by the MeNB in the dual connectivity. As a result, the SeNB is not able to improve the performance of the mobility management and radio resource management for the UE.
Thus, how to improve the performance of the mobility management and radio resource management of the SeNB is an important problem to be solved.

Method of handling simultaneous communications and related communication device


A blower filter device (50) for a respirator system (1) has a filter unit (31) receiving an air filter (30) and a blower unit (65) drawing in the filtered air and generating discharged air. The blower unit has a blower (53) and a driving motor (54). An improved respirator system is provided with the blower filter device having a pressure sensor (55) arranged in the discharged air measuring the pressure of the discharged air, a mass flow sensor (56) arranged in the discharged air measuring the mass flow of the discharged air, or a parameter-determining unit (59, 60) determining an operating parameter of the motor. A control unit (51, 52) determines the volume flow of the discharged air via the measured pressure, the measured mass flow or based on the operating parameter determined and sets the motor as a function of the volume flow determined.

Respirator systems protect the user from particles, gases and/or vapors, which may compromise the quality of the breathing air and be hazardous to health. A respirator system has at least one filter for filtering air and a breathing mask, to which the filtered air is fed. The breathing mask may be a hood, a helmet, a visor or even an oronasal mask or half mask.
To provide especially reliable protection from contaminated air, blower-assisted respirator systems additionally have a blower unit, which has a blower and a motor for driving the blower. The blower unit draws in the air filtered through the filter and generates discharged air, which is fed to the breathing mask. The blower unit is operated such that an overpressure prevails in the breathing mask, so that only filtered air can escape from the filter mask, but no contaminated air can enter the interior of the breathing mask. Respirator systems with a blower filter device assist the user by lowering the airway resistance, unlike conventional gas masks, and this make fatigue-free long-term use possible.
Blower-assisted respirator systems, which are also called "PAPR" (Powered Air-Purifying Respirator) systems, are known, for example, from DE 100 21 581 B4, EP 0 413 555 A1, and DE 689 09 707 T2.
It is decisive, for the breathing protection offered by a blow-assisted respirator system, to rule out reduced pressure in the breathing mask during the inhalation phase, which is achieved by feeding a defined, constant volume flow of filtered air into the breathing mask. It is thus ensured that the inhaled air is supplied exclusively through the feed of air from the blower filter device rather than from the contaminated surrounding area due to possible leaks of the breathing mask, because excess air is steadily flowing through the exhalation valve of the breathing mask into the surrounding area.
It is known that parameters of the respirator system itself and parameters of the surrounding area, in which the respirator system is operated, are taken into account in the mode of operation of the motor of the blower unit in order to make a constant volume flow of filtered air available to the user of the respirator system.
Methods for operating blower-assisted respirator systems are disclosed, for example, in DE 10 2010 031 754 B4, DE 10 2004 013 453 B4, US 2009/0 266 361 A1, WO 2011/019 778 A1, and DE 102 50 414 A1. For example, WO 2011/019 778 A1 thus shows a method for regulating a motor-operated blower-respirator system for supplying a uniform volume flow, where the density of the ambient air or an ambient temperature and an ambient pressure are taken into account for setting a manipulated electric variable of the motor on the basis of two calibration values.


The present invention relates to a lyotropic chromonic liquid crystal composition, a method for manufacturing a lyotropic chromonic liquid crystal coating film and a lyotropic chromonic liquid crystal coating film manufactured thereby. The lyotropic chromonic liquid crystal composition of the present invention includes chromonic liquid crystal compounds and monomers each having opposing acid-base properties. Use of the lyotropic chromonic liquid crystal composition in the formation of optical films leads to improvements in electrical and optical properties such as mechanical strength, an insulating characteristic and a refractive index.

1. Field of the Invention
Aspects of the present invention relate to a lyotropic chromonic liquid crystal composition, a method for the manufacture of a lyotropic chromonic liquid crystal coating film and a lyotropic chromonic liquid crystal coating film manufactured thereby. More particularly, aspects of the present invention relate to a lyotropic chromonic liquid crystal composition having high hardness and improved aggregation stability between liquid crystals, a method for the manufacture of a lyotropic chromonic liquid crystal coating film having high hardness and improved aggregation stability between liquid crystals by using a chromonic liquid crystal composition, and a lyotropic chromonic liquid crystal coating film manufactured thereby, in manufacturing optical films such as a polarizing plate, a color filter, a retardation film, and the like, employed to a picture display device such as a liquid crystal display (LCD) or an organic light-emitting display (OLED), or films employed to microelectronics, optics, communications, computer technology, biosensors, and the like, using a chromonic liquid crystal composition.
2. Description of the Related Art
In a liquid crystal display (LCD) device, for example, optical films having a polarizing film and a retardation film combined therein have been used in causing various polarizing characteristics.
Among these films, the polarizing film that is stretched using polyvinyl alcohol (PVA) with an iodine dye as a polarizer has been generally used. The optical activities of these films are determined by dichroism of the PVA-dye material used. However, since iodine has large sublimation properties, it is disadvantageously poor in durability, such as heat resistance or light resistance, when added as the polarizing element to a polarizing film.
To address this drawback, an azo dye (for example, direct blue or direct red) has been used in place of iodine. The azo dye exhibits weaker dichroism than the iodine dye, while ensuring durability, so that high optical properties may not be properly demonstrated.
Likewise, in an optical compensation film, such as the retardation film, there have been proposed use examples of a laminated film constituted by laminating stretched films as optical compensation films or retardation films, consisting of a combination of stretched films of a denatured cellulose-based film or a denatured polycarbonate-based film, giving a λ/4 retardation film and a λ/2 retardation film, in Japanese Patent No. 3174367, etc. However, in the proposed film, optical axes of the retardation films consisting of stretched films may vary according to the direction in which the films are stretched.
That is to say, the respective films are laminated such that an absorption axis and a retardation axis are at a desired angle by cutting the respective films along directions of optical axes thereof. In more detail, the absorption axis of a polarizing plate is generally parallel with the direction in which the polarizing plate is stretched, and the retardation axis of the retardation film is also parallel with the direction in which the retardation film is stretched. Accordingly, in order to laminate the polarizing plate and the retardation film at an angle of, for example, 45° formed between the absorption axis and the retardation axis, one of the films should be cut in the direction of 45° with respect to the stretched direction of the film. In a case where the film is cut to then be attached, the angle between the absorption axis and the retardation axis is varied for all of the cut films, resulting in a quality change of all products, incurring increased costs and time in the manufacture of the products. Therefore, an optical film coated with a liquid crystal compound having a planar molecular structure as an aqueous organic dye has recently been proposed.
As representative examples, U.S. Pat. Nos. 2,400,877 and 2,544,659 provide methods of producing a light polarizing element by coating a solution of a dichromatic material on the surface of a substrate, simultaneously with evaporating the solvent from the surface of the substrate, orienting the molecule of the dichromatic material as a nematic phase, and moderately solidifying the molecule in the oriented state. The dichromatic nematic material is water or alcohol-soluble organic dye, which is transformed on the surface of a substrate into a nematic phase.
A liquid crystal is a state of matter in which molecules exhibit long-range orientational order and wherein long-range positional order is either reduced (one-dimensional positional order in smectic phases) or absent (nematic phases).
This intermediate ordering places liquid crystals between crystalline solids (which possess both positional and orientational order) and isotropic fluids (which exhibit no long-range order). Solid crystal or isotropic fluid can be transformed into a liquid crystal by changing temperature or by using an appropriate diluting solvent to change the concentration of mesomorphic molecules. Generally, the liquid crystal formed by changing temperature, like in the former case, is called a thermotropic liquid crystal, and the liquid crystal formed by changing the concentration the diluting solvent, like in the latter case, is called a lyotropic liquid crystal.
Alignment of thermotropic liquid crystals is based on a special unidirectional treatment of the plates or substrates that bound the liquid crystalline material. Such techniques are disclosed in U.S. Pat. No. 5,596,434. The '434 patent discloses that the plates are covered with a polymer (such as polyimide) layer which is mechanically rubbed. The direction of rubbing sets the direction of orientation of the thermotropic liquid crystal, i.e., the director, at the substrate, as a result of anisotropic molecular interactions at the interface. The phenomenon of orienting action between the anisotropic (rubbed, for example) substrate and the liquid crystalline alignment is called "anchoring." Alignment by surface anchoring is a standard means of alignment in thermotropic liquid crystalline displays. Surfaces are typically treated with a polymer or a surfactant in order to obtain the desired alignment effects.
Lyotropic liquid crystals are more difficult to align than their thermotropic counterparts. The reason is that most lyotropic liquid crystals are based on amphiphilic materials (surfactants) dissolved in water or oil. Amphiphilic molecules have a polar (hydrophilic) head and a non-polar (hydrophobic) aliphatic tail. When surfactant molecules are in contact with a substrate, their amphiphilic nature generally results in a perpendicular orientation of the molecule with respect to the plane of the substrate. Perpendicular alignment means that the preferred orientation is the so-called homeotropic alignment, in which the optical axis is perpendicular to bounding plates. Here, the concentration and structure of a given molecule plays a great role in the formation of the orientational order of liquid crystals. A general lyotropic liquid crystal has a long column formed by laminating rod-like molecules or discotic or plank-shaped molecules.
Among various classes of lyotropic liquid crystals, lyotropic chromonic liquid crystals (LCLC) are drawing much attention as useful substance. The molecular structures of LCLCs are markedly different from those of conventional lyotropic liquid crystals based on an amphiphilic material with an ionic function group at an end of a flexible, rod-like aliphatic chain molecule in that LCLC molecules have a hydrophilic or ionic group at a rigid, plank-like aromatic molecule. The LCLC family embraces a range of dyes, drugs, nucleic acids, antibiotics, carcinogens, and anti-cancer agents. The molecular and macrostructure of the LCLC are shown in FIGS. 1 and 2. The LCLC is constructed such that heads of hydrophilic groups 1 directed outward and tails of aggregated or micellar shaped hydrophobic groups 2, dissolved in an aqueous solution, as shown in FIG. 1, or the LCLC molecules having hydrophilic groups 3 attached at the periphery of a plank-like aromatic hydrophobic core 4 are laminated, as shown in FIG. 2. This is called self-assembly. The dual character of the self-assembly gives stable alignment characteristics. Accordingly, the LCLC molecules have gained attention as materials used for various optical devices.
The π-π interaction of the aromatic cores is the main mechanism of molecular face-to-face stacking [J. Lydon, Chromonics, in: Handbook of Liquid Crystals (Wiley-VCH, Weinheim, 1998) v. 2B, p. 981 and Current Opin. Col. Inter. Sci. 3, 458 (1998)]. Hydrophilic ionic groups at the periphery of the molecules make the material water-soluble. These materials have become a subject of intensive studies lately as it became clear that they can be used as internal polarizing elements in liquid crystal displays, see T. Sergan et al., Liquid Crystals v. 5, pp. 567-572 (2000)
U.S. Pat. No. 5,948,487 or PCT/US2000/031181, for example, discloses a structure aligned using nematic liquid crystal materials that contain at least one triazine group. U.S. Pat. No. 6,570,632 discloses a method of acquiring an optical film by coating a chromonic material containing Cromolyn (C23H14O11Na2) on a glass substrate, rubbing and aligning, followed by drying to remove a solvent. The alignment structure of the thus formed optical film is shown in FIG. 3.
In the aligned optical film, as seen in FIG. 3, a molecular plane of LCLC molecule 13 is placed on a Y-Z plane of a base film 11, and the long axis of the LCLC molecule 13 is aligned in the Y-axis direction. However, in the alignment structure, the molecular planes of several molecules may not be perfectly aligned on the Y-Z plane or the long axis of the LCLC molecule 13 may be misaligned away from the Y-axis direction.
To solve these problems, aligning methods of a combination of electrostatic layer stacking and shear orientation are disclosed in several literatures: T. Schneider and O. D. Lavrentovich: Langmuir, 2000, 16, 5227; T. Schneider, K. Artyushkova et. al.: Langmuir, 2005, 21, 2300; and U.S. patent publication U.S. 2002/0168511.
The alignment structure of the thus formed optical film is shown in FIG. 4. Poly cations 12 are coated on a base film 11 made of glass or mica, an aqueous violet 20 solution 13, a kind of an anionic LCLC, is coated and aligned by a mechanical shear force induced in the X-axis direction, and unnecessary surplus materials are removed by cleaning and then dried, leaving an electrostatically laminated chromonic liquid crystal structure on the dried film. As shown in FIG. 5, a laminated structure in which the poly cations 12 and the anionic LCLC 13 are repeatedly laminated can be obtained by repeating the aforementioned process.
However, even in the above-described methods, optical films, which are formed by coating an LCLC composition dissolved in an aqueous solution or an organic solvent containing solution, and drying the resulting product, during the self-assembly process of liquid crystal molecules, the liquid crystal molecules are liable to segregation in horizontal and vertical planes. In addition, cracks are likely to occur to liquid crystal compositions remaining due to a volumetric reduction caused when a large amount of solvent is removed in the course of drying the liquid crystal molecules. Further, since the optical films have low hardness and a weak binding force with respect to a base film, they are prone to delamination. Additionally, since cohesiveness between molecular aggregates of a liquid crystal dye is weak, there are several problems including poor stability of a thin film, complicated processing conditions due to humidity in the surrounding of an aqueous solution, and so on. In addition, the fabricated optical film is likely to lose its aligned state to then form an optical isotropic phase when it contacts water.
Therefore, it is necessary to increase the intensity of an interaction between the base film and the liquid crystal dye in consideration of a weak binding strength between the molecular aggregates of the liquid crystal dye and a weak binding strength between the aggregates and the base film.

Lyotropic chromonic liquid crystal composition, method for manufacture of lyotropic chromonic liquid crystal coating film, and lyotropic chromonic liquid crystal coating film manufactured thereby

Korea Institute of Industrial Technology

Industrial Cooperation Foundation Chonbuk National University


A compound of formula I and a method of treatment of diseases, related to modulation of the adenosine A2 receptor system comprising administering a compound of formula

The present invention is directed to the use of adenosine receptor ligands in a method of treatment, control, or prevention of central nervous system disorders.
Adenosine modulates a wide range of physiological functions by interacting with specific cell surface receptors. The potential of adenosine receptors as drug targets was first reviewed in 1982. Adenosine is related both structurally and metabolically to the bioactive nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and cyclic adenosine monophosphate (cAMP); to the biochemical methylating agent S-adenosyl-L-methione (SAM); and structurally to the coenzymes NAD, FAD and coenzyme A; and to RNA. Together adenosine and these related compounds are important in the regulation of many aspects of cellular metabolism and in the modulation of different central nervous system activities.
The receptors for adenosine have been classified as A1, A2A, A2B and A3 receptors, belonging to the family of G protein-coupled receptors. Activation of adenosine receptors by adenosine initiates signal transduction mechanism. These mechanisms are dependent on the receptor associated G protein. Each of the adenosine receptor subtypes has been classically characterized by the adenylate cyclase effector system, which utilizes cAMP as a second messenger. The A1 and A3 receptors, coupled with G1 proteins inhibit adenylate cyclase, leading to a decrease in cellular cAMP levels, while A2A and A2B receptors couple to Gs proteins and activate adenylate cyclase, leading to an increase in cellular CAMP levels. It is known that the A1 receptor system include the activation of phospholipase C and modulation of both potassium and calcium ion channels. The A3 subtype, in addition to its association with adenylate cyclase, also stimulates phospholipase C and so activates calcium ion channels.
The A1 receptor (326-328 amino acids) was cloned from various species (canine, human, rat, dog, chick, bovine, guinea-pig) with 90-95% sequence identify among the mammalian species. The A2A receptor (409-412 amino acids) was cloned from canine, rat, human, guinea pig and mouse. The A2B receptor (332 amino acids) was cloned from human and mouse with 45%) homology of human A2B with human A1 and A2A receptors. The A3 receptor (317-320 amino acids) was cloned from human, rat, dog, rabbit and sheep.
The A1 and A2A receptor subtypes are proposed to play complementary roles in adenosine""s regulation of the energy supply. Adenosine, which is a metabolic product of ATP, diffuses from the cell and acts locally to activate adenosine receptors to decrease the oxygen demand (A1) or increase the oxygen supply (A2A) and so reinstate the balance of energy supply: demand within the tissue. The actions of both subtypes is to increase the amount of available oxygen to tissue and to protect cells against damage caused by a short term imbalance of oxygen. One of the important functions of endogenous adenosine is preventing damage during traumas such as hypoxia, ischaemia, hypotension and seizure activity.
Furthermore, it is known that the binding of the adenosine receptor agonist to mast cells expressing the rat A3 receptor resulted in increased inositol triphosphate and intracellular calcium concentrations, which potentiated antigen induced secretion of inflammatory mediators. Therefore, the A3 receptor plays a role in mediating asthmatic attacks and other allergic responses.
Adenosine is a neuromodulator, able to modulate many aspects of physiological brain function. Endogenous adenosine, a central link between energy metabolism and neuronal activity, varies according to behavioral state and (patho)physiological conditions. Under conditions of increased demand and decreased availability of energy (such as hypoxia, hypoglycemia, and/or excessive neuronal activity), adenosine provides a powerful protective feedback mechanism. Interacting with adenosine receptors represents a promising target for therapeutic intervention in a number of neurological and psychiatric diseases such as epilepsy, sleep, movement disorders (Parkinson or Huntington""s disease), Alzheimer""s disease, depression, schizophrenia, or addiction. An increase in neurotransmitter release follows traumas such as hypoxia, ischaemia and seizures. These neurotransmitters are ultimately responsible for neural degeneration and neural death, which causes brain damage or death of the individual. The adenosine A1 agonists which mimic the central inhibitory effects of adenosine may therefore be useful as neuroprotective agents. Adenosine has been proposed as an endogenous anticonvulsant agent, inhibiting glutamate release from excitory neurons and inhibiting neuronal firing. Adenosine agonists therefore may be used as antiepileptic agents. Adenosine antagonists stimulate the activity of the CNS and have proven to be effective as cognition enhancers.
Selective A2a antagonists have therapeutic potential in the treatment of various forms of dementia, for example in Alzheimer""s disease, and of neurodegenerative disorders, e.g. stroke. Adenosine A2a receptor antagonists modulate the activity of striatal GABAergic neurons and regulate smooth and well-coordinated movements, thus offering a potential therapy for Parkinsonian symptoms. Adenosine is also implicated in a number of physiological processes involved in sedation, hypnosis, schizophrenia, anxiety, pain, respiration, depression, and drug addiction (amphetamine, cocaine, opioids, ethanol, nicotine, cannabinoids). Drugs acting at adenosine receptors therefore have therapeutic potential as sedatives, muscle relaxants, antipsychotics, anxiolytics, analgesics, respiratory stimulants, antidepressants, and to treat drug abuse. They may also be used in the treatment of ADHD (attention deficit hyper-activity disorder).
An important role for adenosine in the cardiovascular system is as a cardioprotective agent. Levels of endogenous adenosine increase in response to ischaemia and hypoxia, and protect cardiac tissue during and after trauma (preconditioning). By acting at the A1 receptor, adenosine A1 agonists may protect against the injury caused by myocardial ischemia and reperfusion. The modulating influence of A2a receptors on adrenergic function may have implications for a variety of disorders such as coronary artery disease and heart failure. A2a antagonists may be of therapeutic benefit in situations in which an enhanced antiadrenergic response is desirable, such as during acute myocardial ischemia. Selective antagonists at A2a receptors may also enhance the effectiveness of adenosine in terminating supraventricular arrhytmias.
Adenosine modulates many aspects of renal function, including renin release, glomerular filtration rate and renal blood flow. Compounds which antagonise the renal affects of adenosine have potential as renal protective agents. Furthermore, adenosine A3 and/or A2B antagonists may be useful in the treatment of asthma and other allergic responses or and in the treatment of diabetes mellitus and obesity.
The current knowledge on adenosine receptors is summarized in various documents including, for example the following publications:
Bioorganic and Medicinal Chemistry, 6, (1998), 619-641,
Bioorganic and Medicinal Chemistry, 6, (1998), 707-719,
J. Med. Chem., (1998),41, 2835-2845,
J. Med. Chem., (1998), 41, 3186-3201,
J. Med. Chem., (1998),41, 2126-2133,
J. Med. Chem., (1999), 42, 706-721,
J. Med. Chem., (1996), 39, 1164-1171,
Arch. Pharm. Med. Chem., 332, 39-41, (1999),
Am. J. Physiol., 276, H11113-1116, (1999) or
Naunyn Schmied, Arch. Pharmacol. 362, 375-381, (2000).
Additionally, WO 01/57008 describes benzothiazolyl urea derivatives and their use as protein kinase inhibitors. According to WO 01/57008, compounds are useful as inhibitors of tyrosine kinases that are important in hyper-proliferative diseases, especially in cancer and in the process of angiogenesis. The compounds of formulae IA and IB below are not encompassed by WO 01/57008.
The present invention is directed to a method of treatment of diseases related to modulation of the adenosine A2 receptor comprising administering a therapeutically effective amount of a compound of formula
wherein
R is lower alkoxy or halogen;
R1/R2 are independently selected from the group consisting of hydrogen, lower alkyl, tetrahydropyran-4-yl and cycloalkyl, said cycloalkyl being unsubstituted or substituted by one or two substituents, selected from the group consisting of halogen, lower alkoxy and hydroxy, or
R1 and R2, together with the N atom to which they are attached, form a heterocyclic ring, selected from the group consisting of
2-oxa-5-aza-bicyclo[2.2.1]heptane,
3-endo-hydroxy-8-aza-bicyclo[3.2.1]octane,
2-aza-bicyclo[2.2.2]octane,
1-oxo-2,8-diaza-spiro[4.5]decane,
3-aza-spiro[5.5]undecane,
8-aza-spiro[4.5]decane,
1-oxa-8-aza-spiro[4.5]decane,
1,8,8-trimethyl-3-aza-bicyclo[3.2.1]octane,
[1,4]oxazepane,
2-oxa-5-aza-bicyclo[2.2.2]octane,
8-oxa-3-aza-bicyclo[3.2.1]octane,
1,4-diaza-bicyclo[3.2.1]octane,
2-aza-bicyclo[2.2.1]heptane, and
3-aza-bicyclo[3.2.1]octane, said heterocyclic ring being unsubstituted or substituted by lower alkyl, or
piperazinyl, said piperazinyl being unsubstituted or having one or two substituents selected from the group lower alkyl, phenyl and oxo or piperidin-1-yl, substituted by a substituent selected from the group xe2x80x94(CH2)nxe2x80x94NRxe2x80x2S(O)2-lower alkyl, xe2x80x94C(O)NRxe2x80x22 and xe2x80x94(CH2)n-phenyl, said phenyl ring being unsubstituted or substituted by lower alkyl and Rxe2x80x2 is independently selected from the group hydrogen and lower alkyl;
X is xe2x80x94Oxe2x80x94 or xe2x80x94CH2xe2x80x94; and
n is 0, 1, 2, 3 or 4
or a pharmaceutically acceptable acid addition salt thereof to a patient in need of such treatment.
Diseases modulated by antagonist activity at the adenosine A2 receptor include Alzheimer""s disease, Parkinson""s disease, Huntington""s disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, drug addiction, such as amphetamine, cocaine, opioids, ethanol, nicotine, cannabinoids, or against asthma, allergic responses, hypoxia, ischaemia, seizure and substance abuse. Additionally, a therapeutically effective amount of a compound of formula I of the present invention may be administered as a sedative, muscle relaxant, antipsychotic, antiepileptic, anticonvulsant and cardiaprotective agent for disorders such as coronary artery disease and heart failure.
The most preferred indications in accordance with the method of treatment of the present invention present invention are those, modulated by A2A receptor antagonistic activity and which include disorders of the central nervous system, for example the treatment or prevention of Alzheimer""s disease, certain depressive disorders, drug addiction, neuroprotection and Parkinson""s disease as well as ADHD.
It has surprisingly been found that the compounds of formula I are adenosine receptor ligands. Specifically, the compounds of the present invention have a good affinity to the A2A-receptor and a high selectivity to the A1- and A3 receptors.
The present invention also relates to novel compounds of formula IA
wherein
R is lower alkoxy or halogen;
R11 and R21, together with the N atom to which they are attached, form a heterocyclic ring, said heterocyclic ring being unsubstituted or substituted by lower alkyl, said heterocyclic ring being selected from the group consisting of
2-oxa-5-aza-bicyclo[2.2.1]heptane,
3-endo-hydroxy-8-aza-bicyclo[3.2.1]octane,
2-aza-bicyclo[2.2.2]octane,
1-oxo-2,8-diaza-spiro[4.5]decane,
3-aza-spiro[5.5]undecane,
8-aza-spiro[4.5]decane,
1-oxa-8-aza-spiro[4.5]decane,
1,8,8-trimethyl-3-aza-bicyclo[3.2.]octane,
[1,4]oxazepane,
2-oxa-5-aza-bicyclo[2.2.2]octane,
8-oxa-3-aza-bicyclo[3.2.1]octane,
1,4-diaza-bicyclo[3.2.1]octane,
2-aza-bicyclo[2.2.1]heptane and
3-aza-bicyclo[3.2.1]octane, or
piperidin-1-yl, substituted by a substituent selected from the group xe2x80x94(CH2)nxe2x80x94NRxe2x80x2S(O)2-lower alkyl, xe2x80x94C(O)NRxe2x80x22 and xe2x80x94(CH2)n-phenyl, said phenyl being unsubstituted or substituted by lower alkyl and Rxe2x80x2 is independently selected from hydrogen and lower alkyl;
X is xe2x80x94Oxe2x80x94 or CH2xe2x80x94; and
n is 0, 1, 2, 3 or 4,
or a pharmaceutically acceptable acid addition salt thereof.
The present invention also is directed to a novel compound of formula IB
wherein
R is lower alkoxy or halogen;
R12 is lower alkyl;
R22 is cycloalkyl, substituted by one or two substituents, said substituents being selected from the group consisting of halogen, lower alkoxy and hydroxy; and
X is xe2x80x94Oxe2x80x94 or CH2xe2x80x94; or a pharmaceutically acceptable salt thereof
Novel compounds of formula IA, wherein X is xe2x80x94Oxe2x80x94, are, for example, the following:
4-benzyl-4-hydroxymethyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
3-aza-spiro[5.5]undecane-3-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
8-aza-spiro[4.5]decane-8-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
2-aza-bicyclo[2.2.2]octane-2-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
1-oxa-8-aza-spiro[4.5]decane-8-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
(R)-4-(1-hydroxy-ethyl)-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
(S)-4-(1-hydroxy-ethyl)-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
4-(methanesulfonylamino-methyl)-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
piperidine-1,4-dicarboxylic acid 4-amide 1-[(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide],
(1R)-1,8,8-trimethyl-3-aza-bicyclo[3.2.1]octane-3-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
2-oxa-5-aza-bicyclo[2.2.2]octane-5-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
1,4-diaza-bicyclo[3.2.1]octane-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide or
(1S,4R)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide.
Novel compounds of formula IA are also those, wherein X is xe2x80x94CH2, for example, the following:
1-oxa-8-aza-spiro[4.5]decane-8-carboxylic acid (4-methoxy-7-piperidin-1yl-benzothiazol-2-yl)-amide,
4-hydroxy-4-(4-methyl-benzyl)-piperidine-1-carboxylic acid (4-chloro-7-piperidin-1-yl-benzothiazol-2-yl)-amide or
4-benzyl-piperidine-1-carboxylic acid (4-chloro-7-piperidin-1-yl-benzothiazol-2-yl)-amide.
Novel compounds of formula IB, wherein X is xe2x80x94Oxe2x80x94, are, for example, the following:
1-(4cis-fluoro-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
1-(4,4-difluoro-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
(cis)-1-(4-methoxy-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
(trans)-1-(4-hydroxy-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
(cis)-1-(4-hydroxy-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea or
(trans)-1-(4-methoxy-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea.
The present invention is also directed to the compounds of formula IA or IB as well as a process for the preparation of a compound of formula IA or IB.
The present invention also relates to a method of treatment for a disease modulated by the adenosine A2 receptor comprising administering a therapeutically effective amount of a compound of formula I, IA or IB, or a pharmaceutically acceptable salts thereof, to a person in need of such treatment. Additionally, the present invention is related to a pharmaceutical composition comprising a compound of formula I, IA or IB, or a pharmaceutically acceptable salt thereof and a pharmaceutically inert carrier. Illnesses responsive to the modulation of the adenosine system include Alzheimer""s disease, Parkinson""s disease, Huntington""s disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, drug addiction, such as amphetamine, cocaine, opioids, ethanol, nicotine, cannabinoids, or against asthma, allergic responses, hypoxia, ischaemia, seizure and substance abuse. Furthermore, compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardiaprotective agents for disorders such as coronary artery disease and heart failure. The most preferred indications in accordance with the present invention are those, which are based on the A2A receptor antagonistic activity and which include disorders of the central nervous system, for example the treatment or prevention of Alzheimer""s disease, certain depressive disorders, drug addiction, neuroprotection and Parkinson""s disease as well as ADHD.
As used herein, the term xe2x80x9clower alkylxe2x80x9d denotes a saturated straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, 2-butyl, t-butyl and the like. Preferred lower alkyl groups are groups with 1-4 carbon atoms.
The term xe2x80x9chalogenxe2x80x9d denotes chlorine, iodine, fluorine and bromine.
The term xe2x80x9clower alkoxyxe2x80x9d denotes a group wherein the alkyl residues is as defined above, and which is attached via an oxygen atom.
The term xe2x80x9cpharmaceutically acceptable acid addition saltsxe2x80x9d embraces salts with inorganic and organic acids, such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methane-sulfonic acid, p-toluenesulfonic acid and the like.
Preferred compounds of the present application for use against diseases, related to modulation of the the A2a receptor are compounds of formula I, wherein X is xe2x80x94Oxe2x80x94, for example the following compounds:
(1S,4S)-2-oxa-5-aza-bicyclo[2.2.1]heptane-5-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
3-endo-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
2-methyl-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
4-benzyl-4-hydroxymethyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
3-aza-spiro[5.5]undecane-3-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
8-aza-spiro[4.5]decane-8-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
2-aza-bicyclo[2.2.2]octane-2-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
1-oxa-8-aza-spiro[4.5]decane-8-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
(R)-4-(1-hydroxy-ethyl)-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
(S)-4-(1-hydroxy-ethyl)-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
4-(methanesulfonylamino-methyl)-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
piperidine-1,4-dicarboxylic acid 4-amide 1-[(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide],
1-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-3-(tetrahydro-pyran-4-yl)-urea,
4-isopropyl-piperazine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
4-phenyl-piperazine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
1-cyclohexyl-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
1-(4cis-fluoro-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
1-(4cis-fluoro-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
(cis)-1-(4-methoxy-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
(trans)-1-(4-hydroxy-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
[1,4]oxazepane-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
(cis)-1-(4-hydroxy-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
2-oxa-5-aza-bicyclo[2.2.2]octane-5-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
(trans)-1-(4-methoxy-cyclohexyl)-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
(1S,4R)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide,
3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-1- (tetrahydro-pyran-4-yl)-urea,
1-cycloheptyl-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea,
1-cyclopentyl-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1-methyl-urea andr
1-cyclopentyl-3-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-urea.
Preferred compounds of formula I, wherein X is xe2x80x94CH2xe2x80x94 of the method of treatment of the present present invention against diseases, responsive to modulation of the A2a receptor are selected from the group consisting of
1-oxa-8-aza-spiro[4.5]decane-8-carboxylic acid (4-methoxy-7-piperidin-1yl-benzothiazol-2-yl)-amide,
4-hydroxy-4-(4-methyl-benzyl)-piperidine-1-carboxylic acid (4-chloro-7-piperidin-1-yl-benzothiazol-2-yl)-amide,
4-benzyl-piperidine-1-carboxylic acid (4-chloro-7-piperidin-1-yl-benzothiazol-2-yl)-amide,
4-methyl-3-oxo-piperazine-1-carboxylic acid (4-methoxy-7-piperidin-1-yl-benzothiazol-2-yl)-amide and
1-(4-chloro-7-piperidin-1-yl-benzothiazol-2-yl)-3-cyclohexyl-urea.
Compounds of formula IA or IB and or pharmaceutically acceptable salts thereof can be prepared by methods known to the art, for example, by processes described below, which process comprises
reacting a compound of formula
with phenyl chloroformate and then with a compound of formula
HNR11R21(3A) or HNR12R22xe2x80x83xe2x80x83(3B)
forming a compound of formula
wherein R and X are as defined above, and R11 and R21 form together with the N atom to which they are attached heterocyclic rings, selected from the group consisting of
2-oxa-5-aza-bicyclo[2.2.1]heptane, 3-endo-hydroxy-8-aza-bicyclo[3.2.1]octane,
2-aza-bicyclo[2.2.2]octane, 1-oxo-2,8-diaza-spiro[4.5]decane, 3-aza-spiro[5.5]undecane,
8-aza-spiro[4.5]decane, 1-oxa-8-aza-spiro[4.5]decane, 1,8,8-trimethyl-3-aza-bicyclo[3.2.1]octane, [1,4]oxazepane, 2-oxa-5-aza-bicyclo[2.2.2]octane,
8-oxa-3-aza-bicyclo[3.2.1]octane, 1,4-diaza-bicyclo[3.2.1]octane,
2-aza-bicyclo[2.2.1]heptane or 3-aza-bicyclo[3.2.1]octane, and which rings may be unsubstituted or substituted by lower alkyl, or is selected from piperidin-1-yl, substituted by xe2x80x94(CH2)n-phenyl, xe2x80x94(CH2)nxe2x80x94NRxe2x80x2S(O)2-lower alkyl, xe2x80x94C(O)NRxe2x80x22 or xe2x80x94(CH2)n-phenyl and wherein the phenyl ring is unsubstituted or substituted by lower alkyl and Rxe2x80x2 is hydrogen
or lower alkyl, independently from each other in case Rxe2x80x22 and n is described above,
and R12 is alkyl and R22 is cycloalkyl, substituted by one or two substituents, wherein the substituents are selected from the group, consisting of halogen, lower alkoxy or hydroxy; or
if desired, converting the compounds obtained into pharmaceutically acceptable acid addition salts.
The compounds of formula IA and IB may be prepared in accordance with process variant a) and with the following scheme 1. Scheme 2 shows the preparation of the intermediate compound of formula (2). 37 Examples are further described in more detail for the preparation of compounds of formula IA and IB.
wherein the substituents are described above.
Preparation of a Compound of Formula IA or IB
To a solution of a compound of formula (2), for example 4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl-amine in dichloromethane is subsequently added pyridine and phenyl chloroformate and the resulting solution is stirred for 45 min at ambient temperature. Then a compound of formula (3A) or (3B), for example (1S,4S)-2-oxa-5-aza-bicyclo[2.2.1]heptane is added and the mixture stirred at ambient temperature for about 15 min and at 40xc2x0 C. for 2.5 h. After cooling to ambient temperature, saturated aqueous sodium carbonate is added, the organic phase is separated and dryed.
The preparation of the starting compound of formula (2) has been described in EP 00113219.0 as follows:
wherein the numbers 1-5 have the following meaning
1 morpholine or piperidine, base, Pd-catalyst,
2H2 and Pdxe2x80x94C, or H2 and Raney-Ni, or TiCl3, or Fe,
3 Ph(CO)NCS,
4 NaOMe,
5 Br2.
R is lower alkoxy or halogen and R3 is piperidin-1-yl or morpholinyl.
Isolation and Purification of the Compounds
Isolation and purification of the compounds and intermediates described herein can be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, extraction, crystallization, column chromatography, thin-layer chromatography, thick-layer chromatography, preparative low or high-pressure liquid chromatography or a combination of these procedures. Specific illustrations of suitable separation and isolation procedures can be had by reference to the Preparations and Examples herein below. However, other equivalent separation or isolation procedures could, of course, also be used.
Pharmaceutically Acceptable Salts of Compounds of Formula IA or IB
The basic groups of compounds of formula IA or IB may be converted to a corresponding acid addition salt. The conversion is accomplished by treatment with at least a stoichiometric amount of an appropriate acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as 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-toluenesulfonic acid, salicylic acid and the like. Typically, the free base is dissolved in an inert organic solvent such as diethyl ether, ethyl acetate, chloroform, ethanol or methanol and the like, and the acid added in a similar solvent. The temperature is maintained between 0xc2x0 C. and 50xc2x0 C. The resulting salt precipitates spontaneously or may be brought out of solution with a less polar solvent.
The acid addition salts of the basic compounds of formula I may be converted to the corresponding free bases by treatment with at least a stoichiometric equivalent of a suitable base such as sodium or potassium hydroxide, potassium carbonate, sodium bicarbonate, ammonia, and the like.
The compounds of formula I and their pharmaceutically acceptable addition salts possess valuable pharmacological properties. Specifically, it has been found that the compounds of the present invention are adenosine receptor ligands and possess a high affinity towards the adenosine A2A receptor and a good selectivity towards A1 and A3 receptors.
The compounds of the invention were investigated in accordance with the following test.
The human adenosine A2A receptor was recombinantly expressed in chinese hamster ovary (CHO) cells using the semliki forest virus expression system. Cells were harvested, washed twice by centrifugation, homogenised and again washed by centrifugation. The final washed membrane pellet was suspended in a Tris (50 mM) buffer containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl2 and 10 mM MgCl2 (pH 7.4) (buffer A). The [3H]-SCH-58261 (Dionisotti et al., 1997, Br J Pharmacol 121, 353; 1 nM) binding assay was carried out in 96-well plates in the presence of 2.5 xcexcg of membrane protein, 0.5 mg of Y si-poly-1-lysine SPA beads and 0.1 U adenosine deaminase in a final volume of 200 xcexcl of buffer A. Non-specific binding was defined using xanthine amine congener (XAC; 2 xcexcM). Compounds were tested at 10 concentrations from 10 xcexcM-0.3 nM. All assays were conducted in duplicate and repeated least two times. Assay plates were incubated for 1 hour at room temperature before centrifugation and then bound ligand determined using a Packard Topcount scintillation counter. IC50 values, the concentration where 50% of the non-specific binding is displaced, were calculated using a non-linear curve fitting program and Ki values calculated using the Cheng-Prussoff equation.
The preferred compounds of the invention have a pKi greater than 7.5.
The compounds of formula I and the pharmaceutically acceptable salts of the compounds of formula I can be used to prepare pharmaceutical compositions. The pharmaceutical compositions of the invention can be administered orally, e.g. in the form of tablets, coated tablets, dragxc3xa9es, hard and soft gelatine capsules, solutions, emulsions or suspensions. The administration of the pharmaceutical compositions of the invention can, also be effected rectally, e.g. in the form of suppositories and parenterally, e.g. in the form of injection solutions.
A therapeutically effective amount of a compound of formula I can be processed with pharmaceutically inert, inorganic or organic carriers for the production of pharmaceutical compositions. Lactose, corn starch or derivatives thereof, talc, stearic acids or its salts and the like can be used, for example, as such carriers for tablets, coated tablets, dragxc3xa9es and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like. Depending on the nature of the active substance no carriers are, however, usually required in the case of soft gelatine capsules. Suitable carriers for the production of solutions and syrups are, for example, water, polyols, glycerol, vegetable oil and the like. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like.
The pharmaceutical of the invention, moreover, contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances.
The present invention also relates to pharmaceutical compositions containing a therapeutically effective amount of a compound of formula I, including compounds of IA or IB, or a pharmaceutically acceptable salt thereof and a therapeutically inert carrier, The present invention also relates to a process for production of a pharmaceutical composition, which comprises bringing one or more compounds of formula I and/or pharmaceutically acceptable acid addition salts thereof and may also include one or more other therapeutically valuable substances into a galenical administration form together with one or more therapeutically inert carriers.
A method of treatment of the control or prevention of diseases based on the adenosine receptor antagonistic activity of the present invention comprises administering a therapeutically effective amount of a compound of formula I, including compounds of IA or IB, or a pharmaceutically acceptable salt thereof to a person in need of such treatment. Illnesses responsive to adenosine receptor antagonistic activity include Alzheimer""s disease, Parkinson""s disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, asthma, allergic responses, hypoxia, ischaemia, seizure and substance abuse. A compound of the present invention may be administered as a sedative, muscle relaxant, antipsychotic, antiepileptic, anticonvulsant and cardiaprotective agent and for the production of pharmaceutical preparations.
The most preferred indications in accordance with the method of treatment of the present invention include disorders of the central nervous system, for example the treatment or prevention of certain depressive disorders, neuroprotection and Parkinson""s disease.
The dosage can vary within wide limits and will, of course, have to be adjusted to the individual requirements in each particular case. In the case of oral administration the dosage for adults can vary from about 0.01 mg to about 1000 mg per day of a compound of formula I or of the corresponding amount of a pharmaceutically acceptable salt thereof. The daily dosage may be administered as single dose or in divided doses and, in addition, the upper limit can also be exceeded when this is found to be indicated.
The following preparation and examples illustrate the invention but are not intended to limit its scope.

Substituted benzothiazole amide derivatives

Abstract: to a person in need of such treatment.


Means are provided for recording, storing, calculating, communicating and reviewing one or more operational aspects of a machine. Insurance costs are based, in part, on activities of the machine operator. A discount may be provided in exchange for recording the operational aspects and providing the recorded information to the insurer. The party may review information and decide whether to provide it to the insurer. The means for reviewing may present comparative information. Information that causes insurance costs to vary may be highlighted. Provided data may be used to verify insurance application information, generate actuarial information or determine insurance rates. Operating data may be reviewed on a display medium so a party can observe how his operating behavior compares to that of other operators of similar machines and may be manipulated so a party can understand how changes in operating behavior can affect his insurance rates.

Conventional methods for determining costs of motor vehicle insurance involve gathering relevant historical data from a personal interview with, or a written application completed by, the applicant for the insurance and by referencing the applicant's public motor vehicle driving record that is maintained by a governmental agency, such as a Bureau of Motor Vehicles. Such data results in a classification of the applicant to a broad actuarial class for which insurance rates are assigned based upon the empirical experience of the insurer. Many factors are deemed relevant to such classification in a particular actuarial class or risk level, such as age, sex, marital status, location of residence and driving record.
The current system of insurance creates groupings of vehicles and drivers (actuarial classes) based on the following types of classifications.
Vehicle:                Age;        manufacturer, model; and        value.
Driver:                Age;        sex;        marital status;
driving record (based on government reports), violations (citations);                at fault accidents; and        place of residence.
Coverage:                Types of losses covered,                    liability,            uninsured or underinsured motorist,            comprehensive, and            collision;                        liability limits; and        deductibles.
The classifications, such as age, are further broken into actuarial classes, such as 21 to 24, to develop a unique vehicle insurance cost based on the specific combination of attributes for a particular risk. For example, the following information would produce a unique vehicle insurance cost:
Vehicle:
Age1997 (seven years old)manufacturer, modelFord, Explorer XLTvalue$18,000Driver:
Age38 years oldsexmalemarital statussingledriving record (based ongovernment reports)violations1 point (speeding)at fault accidents3 points (one at fault accident)place of residence33619 (zip code)Coverage:
Types of losses coveredliabilityyesuninsured or underinsurednomotoristcomprehensiveyescollisionyesliability limits$100,000/$300,000/$50,000deductibles$500/$500
A change to any of this information might result in a different premium being charged, if the change resulted in a different actuarial class or risk level for that variable. For instance, a change in the drivers' age from 38 to 39 may not result in a different actuarial class, because 38 and 39 year old people may be in the same actuarial class. However, a change in driver age from 38 to 45 may result in a different premium because the records of the insurer indicate a difference in risk associated with those ages and, therefore, the age difference results in a change in actuarial class or assigned risk level.
Current insurance rating systems also provide discounts and surcharges for some types of use of the vehicle, equipment on the vehicle and type of driver. Common surcharges and discounts include:
Surcharges:
Business use.
Discounts:
Safety equipment on the vehicle                airbags, and        antilock brakes;
theft control devices                passive systems (e.g. "The Club"), an        alarm system; and
driver type                good student, and        safe driver (accident free).
group                senior drivers        fleet drivers
A principal problem with such conventional insurance determination systems is that much of the data gathered from the applicant in the interview or from the written application is not verifiable, and even existing public records contain only minimal information, much of which has little relevance towards an assessment of the likelihood of a claim subsequently occurring. In other words, current rating systems are primarily based on past realized losses and the past record of other drivers with similar characteristics. None of the data obtained through conventional systems necessarily reliably predicts the manner or safety of future operation of the vehicle by the driver/applicant. Accordingly, the limited amount of accumulated relevant data and its minimal evidential value towards computation of a fair cost of insurance has generated a long-felt need for an improved system for more reliably and accurately accumulating data having a highly relevant evidential value towards predicting the actual manner of a vehicle's future operation by a specific driver or group of drivers.
Many types of vehicle operating data recording systems have heretofore been suggested for purposes of obtaining an accurate record of certain elements of vehicle operation. Some are suggested for identifying the cause for an accident; others are for more accurately assessing the efficiency of operation and/or environmental emissions of a vehicle. Such systems disclose a variety of conventional techniques for recording vehicle operation data elements in a variety of data recording systems. It has even been suggested to detect and record seatbelt usage to assist in determination of the vehicle insurance costs (U.S. Pat. No. 4,667,336).
The various forms and types of vehicle operating data acquisition and recordal systems that have heretofore been suggested and employed have met with varying degrees of success for their express limited purposes. All possess substantial defects such that they have only limited economic and practical value for a system intended to provide an enhanced acquisition, recordal and/or communication system of data which would be both comprehensive and reliable in predicting an accurate and adequate cost of insurance for the vehicle. Since the type of operating information acquired and recorded in prior art systems was generally never intended to be used for determining the cost of vehicle insurance, the data elements that were monitored and recorded therein were not directly related to predetermined safety standards or the determining of an actuarial class or risk level for the vehicle operator. For example, recording data characteristics relevant to the vehicle's exhaust emissions may be completely unrelated to the safety of operation of the vehicle. Further, there is the problem of recording and subsequently compiling the relevant data for an accurate determination of an actuarial profile and an appropriate insurance cost therefor.
Current motor vehicle control and operating systems comprise electronic systems readily adaptable for modification to obtain the desired types of information relevant to determination of the cost of insurance. Vehicle tracking systems have been suggested which use communication links with satellite navigation systems for providing information describing a vehicle's location based upon navigation signals. When such positioning information is combined with maps or geographic information in an expert system, vehicle location is ascertainable. Mere vehicle location, though, will not provide data particularly relevant to safety of operation unless the data is combined with other relevant data in an expert system which is capable of assessing whether the roads being driven are high-risk or low-risk with regard to vehicle safety.
On-line Web sites for marketing and selling goods have become common place. Many insurers offer communication services to customers via Web sites relevant to an insured profile and account status. Commonly assigned pending application U.S. Ser. No. 09/135,034, filed Aug. 17, 1998, now U.S. Pat. No. 6,064,970, discloses one such system. Customer comfort with such Web site communication has generated the need for systems which can provide even more useful information to customers relative to a customer's contract with the insurer. Such enhanced communications can be particularly useful to an insured when the subject of the communications relates to cost determination, or when the subject relates to prospective reoccurring insurable events wherein the system can relate in the existing insured's profile with some insurer-provided estimates to the effect that a future event or method of operating a unit of risk would have on an estimated cost of insuring the unit of risk.
The present invention contemplates a new and improved monitoring, recording, processing and communicating system for an insured unit of risk, such as a machine, which primarily overcomes the problem of accurately determining cost of insurance based upon data which does not take into consideration how a specific unit of risk or machine is operated or decisions made by a particular unit of risk owner or operator. The subject invention will base insurance charges with regard to current material data representative of actual decisions made by the operator and/or operating characteristics to provide a more precise classification rating of an operator or the unit in an actuarial class which has a vastly reduced rating error over conventional insurance cost systems. Additionally, the present invention allows for frequent (e.g., monthly, quarterly, semiannually, etc.) adjustment to the cost of insurance because of the changes in operating behavior patterns. This can result in insurance charges that are readily controllable by individual operators. The system is adaptable to current electronic operating systems, tracking systems and communicating systems for the improved extraction of selected insurance related data. In addition, the system provides for enhanced and improved communication and analysis of the relevant acquired data, cost estimates of insuring events and customer insured profiles through a personal computer and/or Internet/Web site.
Another deficiency in prior art systems is that such systems were never intended to allow the operator to control whether to submit to the insurer the data elements monitored and recorded from the vehicle or machine. The system solves this problem by providing the means for the operator to control the submission of information to the insurer and by allowing the operator to understand how modifying operational behavior affects the cost of insurance.

This patent is subject to a terminal disclaimer.

Monitoring system for determining and communicating a cost of insurance


A bath accessory collection, holder, and storage device includes a base, and a scoop, removably couplable to the base, having a drain for draining liquid therefrom. A handle is attached to the scoop, which is used to wield the scoop. A hanger is carried by one of the base and the scoop, which is used to suspend at least one bath accessory thereon. In another embodiment, there is a clamp carried by one of the base and the scoop, which is capable of grippingly holding at least one bath accessory. The base is furnished with a shelf for receiving and supporting bath accessories thereon. An engagement element is carried by one of the base and the scoop, and a detachably engagable complemental engagement element carried by the other of the base and the scoop. Preferably, the device presents the appearance of an object or thing designed to promote interest in the device by children and for encouraging use of the device when the scoop is attached to the base.

In an effort to make bathing a fun, enjoyable experience, many parents provide their children with bath toys for the children to play with during bath time. The problem with bath toys is that they are often left in the bottom of a tub following use of the tub. This is a problem, because the moist environment at the bottom of the tub on and around the bath toys promotes the buildup of mold and bacteria on the bath toys. The proliferation of mold and bacteria on bath toys poses serious health concerns for young children. In fact, it is recommended that bath toys be properly rinsed and stored after use so that they will readily dry to prevent the buildup of mold and bacteria. However, rinsing and storing bath toys is very inconvenient. Each toy must be picked up and rinsed separately, and then placed on a rack or shelf for drying. Because collecting, rinsing, and properly storing bath toys is so inconvenient, and because there is nothing in the prior art for use in doing so, many people fail to do so and just leave the bath toys in the bottom of the tub so as to be prone to mold and bacteria build up.
Given these and other deficiencies in the art, there is a need in the art for easy and efficient way to collect, rinse, and store bath toys, and, moreover, for holding and storing bath toys and other bath accessories, including, for instance, bath poufs, wash cloths, soap, shampoo, conditioner, and other accessories commonly used for bathing.