In one embodiment, an apparatus comprises logic for detecting stolen authentication cookie attacks. A first transport connection is established between a client and a gateway server, where the first transport connection is authenticated by the gateway server. A first authentication cookie is associated with a client session, between the client and the gateway server, that includes the first transport connection. A second transport connection is established at the gateway server. A request is received over the second transport connection. The request includes the first authentication cookie to associate the second transport connection with the client session. A second authentication cookie is generated for the client session and is returned over the second transport connection. Thereafter, a determination is made whether the second authentication cookie is received over the first transport connection. An attack is detected when the second authentication cookie is not received over the first transport connection.

The approaches described in this section could be pursued, but are not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated herein, the approaches described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.
In a typical authenticated HyperText Transfer Protocol (HTTP) session, a client is required to present authentication credentials such as, for example, a username/password or some other authentication certificate in order to gain access to resources provided by an HTTP server. At the end of the authentication phase, the client is given an authentication cookie that is used to verify the HTTP requests sent by the client during the HTTP session. Typically, a client can concurrently open multiple Transmission Control Protocol (TCP) connections to send HTTP requests to the HTTP server during an active authenticated HTTP session. The client includes the authentication cookie for the session with each HTTP request sent on any of the TCP connections.
It is possible for an adversary to use malicious code to obtain an authentication cookie that is stored on a client, and thereafter to use the authentication cookie in order to gain unauthorized access by masquerading as the legitimate client. This type of attack, in which an unauthorized entity obtains an authentication cookie from a legitimate client and uses the cookie to gain unauthorized access, is referred to herein as a "stolen cookie attack." For example, the adversary may use some sort of phishing attack to gain access to the cookie file stored at the client and to read any authentication cookies stored therein, or use a network sniffer to intercept the messages sent on clear-text transport connections. Once the adversary obtains an authentication cookie, the adversary can gain unauthorized access by masquerading as the legitimate client since the cookie is used to keep track of the authentication state of the client.
Although the above stolen cookie attack scenario is presented herein for HTTP sessions, it is noted that this attack scenario is not unique to sessions established over the HTTP protocol. Rather, the above attack scenario is possible for any application, presentation, and/or session layer protocol that allows authenticated sessions over a transport layer protocol.

Detecting stolen authentication cookie attacks


The present invention is directed to a water- and oil repellency-imparting preparation for fibrous and other substrates, the preparation comprising a fluorinated polymer and a tacking monomer, oligomer or polymer containing at least one anhydride functional group or a group capable of forming an anhydride functional group, optionally together with an anhydride-forming catalyst, such as sodium hypophosphite. The preparation can further optionally comprise other additives such as, for example, an extender; a softener; an antioxidant; a surfactant; and/or a plasticizer.

This invention relates to textile treatment compositions for imparting durable water and soil resistance to fibrous substrates, including textiles.
The treatment of fibrous substrates with fluorochemical compositions to impart water and oil repellency is known; see, for example, Banks, Ed., Organofluorine Chemicals and Their Industrial Applications, Ellis Horwood Ltd., Chichester, England, 1979, pp. 226-234.
Generally, copolymers having a water- and oil-repellence are copolymers each comprising a (meth)acrylate monomer containing a perfluoroalkyl group capable of directly giving a water- and oil-repellence, a fluorine-free monomer capable of improving an adhesiveness to the surfaces of materials to be treated such as fibers, etc., through an affinity thereto, and a monomer capable of giving a durability through self-crosslinking or reaction with reactive groups on the surface of the materials to be treated, typical of which are copolymers having N-methylol groups combined with the main chain, such as copolymers of perfluoroalkyl group-containing (meth)acrylate and N-methylol acrylamide-based copolymers. However, when the fibrous or other substrate is treated with these copolymers, formaldehyde is produced, which is highly undesirable from an environmental and safety standpoint.
The present invention is directed to treatment preparations useful for the treatment of textiles and other webs to provide substantially permanent, durable water and soil repellency to fibrous substrates and other materials without the production of formaldehyde. More particularly, the invention is directed to preparations that comprise a fluorinated polymer and a monomer, oligomer or polymer selected from those containing an anhydride functional group or capable of forming an anhydride functional group (referred to herein and in the appended claims as a xe2x80x9ctacking polymerxe2x80x9d). It has been found by the applicants that this monomer, oligomer or polymer increases the performance and durability of the fluoropolymer by an unknown mechanism, possibly (without being bound by theory) by xe2x80x9ctackingxe2x80x9d the fluoropolymer to the surface of the fabric.
By xe2x80x9cfluorinated polymerxe2x80x9d or xe2x80x9cfluoropolymerxe2x80x9d is meant that the polymer will contain some perfluorinated or partially fluorinated alkyl chains to impart water and oil repellency to coated objects. It may additionally be advantageous for the polymer to contain other groups such as normal alkyl chains; groups that can increase the water solubility or stability of the suspension of the polymer, such as chains of polyethylene glycol or other polar groups; one or more different groups that can crosslink to each other or to the material being coated; or groups that increase polymer flexibility, flame retardancy, the softness of a textile, or resistance to bacteria or mildew.
The preparation can be applied, e.g., to a fibrous substrate by contacting the substrate with the preparation, for example, by immersing it in a bath of the composition or by spraying the composition onto the substrate. The fluoropolymer and the tacking polymer may be added together to the bath, or the tacking polymer may be added to the bath following initial exposure of the substrate to the fluoropolymer. The treated substrate is then cured to remove the solvent therefrom and allow reaction with the textile.
The composition of this invention imparts desirable water and oil repellency to the substrates treated therewith without adversely affecting other desirable properties of the substrate, such as soft hand (or feeling). The composition allows for nonformaldehyde releasing binding to cotton and other substrates. The composition of the present invention can be used for providing water and oil repellency to fibrous substrates such as textiles, papers, non-woven articles or leather.
This invention is further directed to the yarns, fibers, fabrics, textiles, finished goods or other fibrous substrates treated with the water- and soil-resistant preparations of the invention. Such fibrous substrates exhibit a greatly improved, durable water and soil repellency. By xe2x80x9cdurable water and soil repellencyxe2x80x9d is meant that the textile, web or other substrate will exhibit a repellency or resistance to water and oily soils even after multiple launderings.
As used herein and the appended claims, the term xe2x80x9c(meth)acrylatexe2x80x9d refers to either the acrylate or the methacrylate compound, unless otherwise indicated.
The fluoropolymer useful in the invention comprises fluoroaliphatic radical-containing agents. These fluorinated monomeric, oligomeric or macromonomeric agents may be chosen from any of those that are useful for the treatment of fabrics to obtain repellency of water and oily and aqueous stains. Fluoroaliphatic radical-containing agents include condensation polymers such as polyesters, polyamides or polyepoxides and vinyl polymers such as acrylates, methacrylates or polyvinyl ethers. Further examples of such fluoroaliphatic radical-containing water and oil repellency-imparting agents include those formed by the reaction of perfluoroaliphatic thioglycols with diisocyanates to provide perfluoroaliphatic group-bearing polyurethanes. Another group of compounds which can be used are fluoroaliphatic radical-containing N-methylolcondensation products. Further examples include fluoroaliphatic radical-containing polycarbodiimides, which can be obtained by, for example, reaction of perfluoroaliphatic sulfonamido alkanols with polyisocyanates in the presence of suitable catalysts. The fluoropolymers may include xe2x80x94CF3 and xe2x80x94CHF2 end groups, perfluoroisopropoxy groups (xe2x80x94OCF(CF3)2), 3,3,3-trifluoropropyl groups, and the like. The polymers may include vinyl ethers having perfluorinated or partially fluorinated alkyl chains.
The fluoropolymer preferably comprises one or more fluoroaliphatic radical-containing acrylate or methacrylate monomers. Such monomers have the structure of Formula I, below:
In the compound of Formula I, for example:
m is 0 to 2;
n is 0 or 1;
o is 1 or 2;
A is xe2x80x94SO2xe2x80x94, xe2x80x94N(W)xe2x80x94SO2xe2x80x94, xe2x80x94CONHxe2x80x94, xe2x80x94CH2xe2x80x94, or xe2x80x94C F2xe2x80x94;
R is a linear, branched, or cyclic fluorocarbon, including fully or partially fluoronated hydrocarbons, wherein R may be, for example, a C1 to C30 fluorocarbon;
W is hydrogen or C1-C4 lower alkyl; and
X is acrylate, methacrylate, or a carbon-carbon double bond.
Fluoroaliphatic radical-containing agents are available commercially or they may be synthesized. Commercially available agents include FX-13, a fluorinated acrylate from 3M; FX-14, a fluorinated methacrylate from 3M; Zonyl TA-N, a fluorinated acrylate from DuPont; Zonyl TM, a fluorinated methacrylate from DuPont; and FAVE(trademark) products from AlliedSignal (Morristown, N.J.).
In a presently preferred embodiment of the invention, the fluoropolymer comprises a) a fluoroaliphatic radical-containing agent, (b) stearyl (meth)acrylate; and (c) a chlorine-containing compound, such as vinylidene chloride, vinyl chloride, 2-chloroethylacrylate, or 2-chloroethyl vinyl ether.
The fluoropolymer may be further copolymerized with i) hydroxyalkyl (meth)acrylate to increase the performance and permanency of the resulting copolymer, ii) a compound such as poly(ethylene glycol) (meth)acrylate to improve solubility of the copolymer in water, and/or iii) a chain terminator, such as dodecanethiol, mercaptosuccinic acid, or other similar compounds, which acts to keep the molecular weight of the polymer low so that it is more readily dispersible in water and can better penetrate the fabric.
The tacking polymer as the other component of the present treatment preparation is selected from those monomers, oligomers or polymers that contain at least one anhydride functional group or at least one group capable of forming an anhydride functional group. Such monomers can include carboxylic acids and carboxylic acid anhydrides and can include, but are not limited to, maleic acid, acrylic acid, itaconic acid, bisacrylamidoacetic i acid, 3-butene-1,2,3-tricarboxylic acid, 2-carboxyethyl acrylate, methacrylic acid, allylsuccinic acid, citraconic acid, 4-methacryloxyethyl trimellitic acid, 4,4xe2x80x2-hexafluoro-isopropylidenebisphthalic acid, and the like, and the anhydride form of any of the above acids. The tacking polymer may be a copolymer or a graft-copolymer of any of the above monomers, with each other or with other monomers. Examples include, but are not limited to, poly(acrylic acid), poly(butadiene/maleic acid), poly(poly(maleic anhydride/1-octadecene), polybutyl acrylate/acrylic acid), poly(ethyl acrylate/acrylic acid), poly(ethylene/acrylic acid), poly(maleic acid), poly(ethylene/maleic acid), poly(mthacrylic acid), poly(methylmethacrylate/methacrylic acid), poly(styrenesulfonic acid/maleic acid), poly(vinyl methyl ether/maleic acid), poly(vinyl methyl ether/monobutyl maleate), poly(vinyl methyl ether/monoethyl maleate), poly(vinyl methyl ether/monoisopropyl maleate), starch and poly(acrylamide/acrylic acid) graft, poly(azelaic anhydride), and poly(maleic anhydride). The salts of the above monomeric, oligomeric or polymeric acids are also useful in this invention.
Hydroxyalkyl (meth)acrylate for use in the invention as an optional component of the fluoropolymer includes, for example, 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, and the like. When the hydroxyalkyl (meth)acrylate is copolymerized, further improvement of durability can be attained with simultaneous use of a crosslinking agent such as butane tetracarboxylic acid, poly(acrylic acid), and the like.
To form the present oil- and water-repellent treatment preparations of the invention, a fluoropolymer and a tacking polymerxe2x80x94with or without optional additives such as i) hydroxyalkyl (meth)acrylate, ii) a compound such as poly(ethylene glycol) (meth)acrylate to improve solubility of the copolymer in water, and/or iii) a chain terminatorxe2x80x94are diluted in water and mixed together with an anhydride-forming catalyst (as necessary) and, optionally, other components such as an antioxidant, a permanent softener/extender, and/or other additives. In a presently preferred embodiment, the permanent softener/extender is a copolymer or graft-copolymer of an anhydride-forming monomer and a soft, hydrophobic monomer (e.g., butadiene, ethylene, isopropylene, and the like).
Anhydride-forming catalysts that can be employed in the preparations of the present invention include, but are not limited to, alkali metal hypophosphites, alkali metal phosphites, alkali metal polyphosphates, and alkali metal dihydrogen phosphates. Some examples of such catalysts are NaH2PO2, H3PO2, Na3PO4, Na2HPO4, NaH2PO4, and H3PO4.
The anhydride functional group will bind chemically with any substrate (including a particular fiber, yarn, fabric, or finished good) with available primary or secondary amines, hydroxyls, sulfhydryls, or metal oxides. For example, cellulosic-based webs such as paper, cotton, rayon, linen, and jute contain hydroxyls. Wool, which is a proteinaceous animal fiber, contains hydroxyls, amines, carboxylates, and thiols (disulfides).
The treatment preparation may comprise from about 1% to about 10% of the fluoropolymer, from about 1% to about 10% tacking polymer, and from 0% to about 7% anhydride-forming catalyst in water.
This invention is further directed to the fibers, yarns, fabrics, textiles, webs, or finished goods (encompassed herein under the term xe2x80x9cfibrous substratesxe2x80x9d) treated with the water- and oil-repellent composition. Such fibrous substrates exhibit a greatly improved, xe2x80x9cdurable water and oil repellencyxe2x80x9d; that is, they remain water- and oil-repellent, even after multiple launderings, while retaining the other desirable properties of the untreated substrate.
The fibrous substrates of the present invention include fibers, woven and non-woven fabrics derived from natural or synthetic fibers and blends of such fibers, as well as cellulose-based papers, leather, and the like. They can comprise fibers in the form of continuous or discontinuous monofilaments, multifilaments, staple fibers, and yarns containing such filaments and/or fibers, and the like, which fibers can be of any desired composition. The fibers can be of natural, manmade, or synthetic origin. Mixtures of natural fibers and synthetic fibers can also be used. Included with the fibers can be non-fibrous elements,, such as particulate fillers, binders, sizes, and the like. The fibrous substrates of the invention are intended to include fabrics and textiles, and may be a sheet-like structure [woven (including jacquard woven for home furnishings fabrics) or non-woven, knitted (including weft inserted warp knits), tufted, or stitch-bonded] comprised of fibers or structural elements. Examples of natural fibers include cotton, wool, silk, jute, linen, and the like. Examples ;of manmade fibers derived primarily from natural sources include regenerated cellulose rayon, cellulose acetate, cellulose triacetate, and regenerated proteins. Examples of synthetic fibers include polyesters (including polyethyleneglycol terephthalate), polyamides (including nylon, such as Nylon 6 and 6,6), acrylics, olefins, aramids, azlons, modacrylics, novoloids, nytrils, spandex, vinyl polymers and copolymers, vinal, vinyon, and the like, and hybrids of such fibers and polymers.
The fluoropolymer/tacking polymer preparation of the present invention is applied as a solution or dispersion/emulsion to the fibrous substrate to be treated by methods known in the art such as by soaking, spraying, dipping, fluid-flow, padding, and the like. The fluoropolymer and the tacking polymer may either be applied simultaneously or the tacking polymer may be applied following application of the fluoropolymer. It is believed that reactive groups on the tacking polymer react with the fibrous material, by covalent bonding during cure, to attach to the fibrous substrate and to thus tack or otherwise hold the fluoropolymer durably to the substrate. The curing can take place either before or after the treated textile is removed from the solution and dried, although it is generally preferred that the cure occur after the drying step. The fibrous substrate may then be rinsed in water to remove any excess catalyst and polymer and dried to give the durable water- and soil-repellent textiles, webs and other fibrous substrates of the invention.
In applying the copolymer composition of the invention to the fibrous substrate to be treated, the pH range should be chosen to be compatible with the reactants. The process temperature can vary widely. However, the temperature should not be so high as to decompose the reactants or so low as to cause inhibition of the reaction or freezing of the solvent. Unless specified to the contrary, the processes described herein take place at atmospheric pressure over a temperature range from ambient temperature to an elevated temperature that is below the boiling point of the solvent used, preferably from about 10xc2x0 C. to about 110xc2x0 C. more preferably from about 20xc2x0 C. to about 60xc2x0 C. and most preferably at 20xc2x0 C. Conveniently, the processes will be at ambient temperature. The process (cure) temperature can also vary widely, depending on the reactivity of the reactants. Unless specified to the contrary, the curing process described herein takes place at atmospheric pressure over a temperature range from about 110xc2x0 C. to about 250xc2x0 C. The time required for the processes herein will depend to a large extent on the temperature being used and the relative reactivities of the starting fibrous substrate and water-repellent polymeric preparation. Therefore, the time of exposure of the textile to the catalyst and the polymers in solution can vary greatly, for example from about a few seconds to about two hours. Normally, the exposure time will be from a few seconds to ten minutes. Unless otherwise specified, the process times and conditions are intended to be approximate.

Oil- and water-repellent finishes for textiles


For stacking flat articles (2), a stacking shaft (10) including a pusher (11) for removing stacks from the shaft is used and for supplying the articles (2) into the stacking shaft (10) a supply support (12) is used. The supply support (12) is oriented towards the opening of the stacking shaft (10) at an inclination from above and the completed stacks (1) are pushed out in a direction opposite the supply direction. With this arrangement, it is possible to resume the supply operation after an interruption necessary for the pushing-out, before the stack (1) is pushed out of the stacking shaft (10) completely, and thereby results in very short cycle times. The stacking method is suitable in particular for stacking folded printed products being supplied in the supply stream parallel to their folded edges.

1. Field of the Invention
The invention is related to a method and a device for stacking flat articles, in particular for stacking printed products.
2. Description of Related Art
It is known to deposit printed products in stacking shafts or in a similar device for the purpose of producing stacks of printed products. Such devices usually comprise a bottom and guide walls standing vertically on the bottom and they are open on the top for the supply of the printed products. In order to reduce to a minimum the free fall of the printed products during stacking, the position of the bottom or of the supply system is often adapted to the height of the stack already present in the shaft, so that every printed product can be slid substantially horizontally onto the previously deposited printed product or onto the shaft bottom.
For producing cross stacks, in which the printed products are stacked in layers or product groups each respectively rotated by 180xc2x0 relative to one another, for example, the bottom of the stacking shaft is designed for being rotated, and at least one intermediate bottom, which is removable from the shaft, is provided. Whenever a product group has been deposited, the bottom with the groups already stacked on it is rotated by 180xc2x0 while the printed products for the subsequent product group are being stacked on the intermediate bottom. When the bottom with the stack is again positioned after rotation, the intermediate bottom, if so required, is lowered into the stacking shaft and is then pulled out of the shaft so that the printed products stacked on the intermediate bottom are deposited on the rotated stack.
When a stack is completed, parts of the vertical guide walls or shaft walls are removed, if so required, and the stack is pushed out of the stacking shaft, usually transverse to the supply direction (or transverse to its projection onto the plane of the stacking shaft bottom, respectively) or in the supply direction. During the whole pushing-out process, the supply has to be interrupted or printed products being supplied have to be pre-stacked on the intermediate bottom.
In many cases, the supply stream is split-up to supply two stacking shafts such that while printed products are being supplied to one shaft, a finished stack is being pushed out of the other stacking shaft.
From the above brief description of the stacking processes as known in the printing field, it is evident that, for their implementation, particularly with high performance capacities or with short cycle times, respectively, rather elaborate devices are necessary. Such elaborate devices require a lot of space.
It is an object of the invention to create a method for stacking flat articles, which may be implemented with very simple devices and in little space while still allowing high unit processing capacities. It is a further object of the invention to create a device for carrying out the method according to the invention.
In accordance with the invention, the flat articles are supplied to the stacking shaft lying loosely on a supply support or else held clamped between two supply supports, for example in an imbricated formation with the leading edges positioned on the top of the formation. The supply support is, for example, a conveyor belt that brings the articles at an inclination from above toward a supply side of the stacking shaft and advantageously to a position just above the stacking shaft, where the supply support ends. The flat articles are driven by the supply support beyond the end thereof and against a side of the stacking shaft disposed opposite the supply side. The flat articles from the supply support into the stacking shaft at the latest, when their leading edge has reached the opposite side of the stacking shaft.
The completed stacks are pushed out in a pushing-out direction opposite to the supply direction (pushing-out direction opposite to the projection of the supply direction onto the plane of the stacking shaft bottom), i.e. through the supply side of the stacking shaft. For the pushing operation a per se known pusher is used. The pushing movement of the pusher starts at the side opposite the supply side of the stacking shaft and is directed toward the supply side. For returning the pusher back to its starting position, the pusher is moved outside of the stacking shaft, for example, underneath the stacking shaft or besides the stacking shaft.
The article supply is interrupted for a first part of the pushing movement. However, the supply can be resumed as soon as the trailing side of the pushed stack has passed the one point in the stacking shaft, at which a further supplied article comes into contact with the stack to be pushed out, i.e., at which this article would come into conflict with the stack. The article supply does not have to be interrupted for at least as long as the complete pushing operation takes as is necessary with known stacking methods; only a fraction of this time is sufficient. Therefore, stacking with the method according to the invention allows shorter cycle times or a higher capacity, respectively, and/or it allows shorter supply interruptions or less buffered articles, respectively, which means easier handling than is the case with known stacking methods.
The supply interruption necessary for the pushing-out becomes shorter, the more steeply from above supply takes place and the longer a free fall into the stacking shaft, i.e. a fall not guided by the supply support, can be tolerated. Because articles having a greater inherent stiffness can still be stacked well after a longer free fall than more flexible articles, the method in accordance with the invention is particularly adapted for stacking stiffer articles. If the method according to the invention is used for folded printed products, these are advantageously supplied to the stacking shaft in a direction parallel to their folded edge (i.e., for tabloid newspapers with a single fold or for newspapers folded twice: in longitudinal direction), because these products have a significantly greater stiffness parallel to the folded edge than transverse to it. Such supply provides the further advantage, that pushing-out of the stack is directed also parallel to the folded edge, i.e. in the one direction, in which stack stability for folded printed product stacks is greatest.
The method in accordance with the invention is therefore suitable in particular for stacking folded printed products, wherein the products are supplied parallel to their folded edges and the stack is pushed out in the opposite direction, once again parallel to the folded edges. For producing cross stacks, the printed products advantageously are supplied in an imbricated stream with alternating groups of correspondingly oriented products, wherein for supply interruptions the imbricated stream comprises gaps or the printed products are temporarily stopped or dammed.
The device for carrying out the method according to the invention comprises a stacking shaft and a supply support leading from above at an incline towards the supply side of the stacking shaft and ending above the opening of the stacking shaft (directly at the supply side or between the supply side and the opposite side). Furthermore, there is a pushing means that is movable through the stacking shaft in a pushing direction opposite the supply direction and returnable into its starting position on the side of the stacking shaft opposite the supply side not through the stacking shaft. If so required, the device also comprises means for interrupting the supply stream of flat articles.

Method and device for stacking flat articles


A cable connector assembly (100) comprises a mating member (3), a printed circuit board (2), a LED (24) attached to the printed circuit board, a cable (6), a light pipe (4) having a visible area (431), an insulative shell (1), and a ring member (5). The cable has a positive wire (61) and a negative wire (62) connected with the mating member (3), and a strain relief portion (64) molded on the wires and neighboring to said light pipe. A detective contact (631) is connecting with the cable. The insulative shell encloses the printed circuit board, the cable and the mating member. The visible area (431) is exposed out of the insulative shell. The ring member has a slick loop portion (51) located in said light pipe and a retaining portion (52) with a rugged exterior surface, and said strain relief portion is molded on the retaining portion.

1. Field of the Invention
The present invention generally relates to a cable connector assembly, and more particularly to a cable connector assembly transmitting power signal.
2. Description of Related Art
Nowadays, cable connector assemblies are widely used in an electronic equipment, especially for transmitting power, and the performance of the cable connector assembly directly impacts on the entire electronic equipment whether can normally run.
A conventional cable connector assembly comprises a printed circuit board, a Light Emitting Diode (LED) attached to the printed circuit board to indicate the working status of the cable connector assembly, a light pipe receiving the LED, a cable with a plurality of wires, a plurality of contacts connected with the cable, a columnar mating member, and an insulated shell enclosing the printed circuit board, the LED, the light pipe and the mating member partially. The wires include a positive wire and a negative wire, both of them comprise an inner conductor and an insulative outer jacket respectively. The outer jackets of the positive wire and the negative wire have different colors to be distinguished. The cable also defines a fuscous strain relief portion on a front part thereof, but the strain relief portion may prevent the light from the LED passing therethrough, so as to it may be difficult for users to observe actual working status of the cable connector assembly as the light weaken. Therefore, a ring member is designed between the light pipe and the strain relief portion in field to avoid aforementioned disadvantage effectively. However, the strain relief member may be unstable with the ring member received in the light pipe wholly.
Hence, it is desirable to have an improved structure to overcome the above-mentioned disadvantages of the prior art.

Cable connector assembly with an improved ring member


The invention relates to a disc-shaped counter, in particular a casino chip, essentially consisting of at least one ring-shaped plastic part and a filler piece held inside a recess in this plastic part, which is applied on to the filler piece in such a way that the plastic ring surrounds the rim of the filler piece radially and axially in an at least partly form-fitting fashion. The filler piece and/or plastic ring contain a material that is detectable in slot-machines. The plastic ring is preferably applied on to the filler piece by a plastic injection moulding process. The counter according to the invention has a more attractive design, is considerably easier and cheaper to produce, and has greater durability, than conventional counters with inserts.

The invention relates to a disc-shaped counter in the form of a plastic ring with a filler piece, according to the introductory part of claim 1. Examples of possible applications of the subject-matter of the present invention are: playing chips for casinos or amusement arcades, tokens for sales promotions, value-tokens, gaming machine tokens, parking tokens, shopping tokens, and identity tokens e.g. for use in hotel chains.
A disc-shaped plastic counter of this kind is known for example from the subject-matter of EP 444373 A1. In this known plastic counter, the filler piece is inserted in a central recess of a plastic ring, the filler piece being pressed into, and held in place by, an inner peripheral annular groove in the plastic ring.
One drawback of this technique is the increased assembly and logistical costs due to the fact that, after the plastic part and the filler piece have been separately produced, it is necessary to insert the filler piece into the central recess of the plastic part in a separate working step.
Another drawback is that the joint between the outer ring-shaped part and the inner filler piece is a simple sticking joint (frictional connection); such a snap-in connection is not necessarily capable of withstanding heavy stresses.
A further drawback of the embodiments according to EP 444373 A1 is that the filler piece, which is the element which is stamped or engraved with the significant information, is inlaid in the plastic ring about level with the surface of the latter, and is thus exposed to increased mechanical wear and tear (e.g. scratching)xe2x80x94shortening the useful life of disc-shaped plastic counters of this type.
Nor is it known, in conventional disc-shaped plastic counters of this kind that are used as tokens, to insert a filler piece which could render the tokens suitable for use in slot-machines, since the appropriate additional metallic materials are not employed.
Therefore the problem which lies at the basis of the invention is to develop a plastic counter of the kind stated at the outset so that it is more attractive in appearance; considerably easier and cheaper to produce; more durable; and also suitable for use in conventional slot-machines (e.g. gaming machines).
The essential features of the invention are that the disc-shaped counter essentially consists of at least one ring-shaped plastic part and a filler piece held inside a recess in this plastic part, which is applied on to the filler piece in such a way that the plastic ring surrounds the rim of the filler piece radially and axially in an at least partly form-fitting fashion, and that the filler piece and/or plastic ring contains a material that is detectable in conventional slot-machines.
The plastic ring is preferably applied on to the filler piece by an injection moulding process, but can also be applied by other methods such as bonding, pressing, pouring, shrinking on, clamping on, or the like.
A completely secure form-fitting joint is thus formed between the plastic part and the rim of the filler piece, without any significant mechanical stresses; the need for further processing of the plastic counter is eliminated; and the useful life of the plastic counter is considerably extended in comparison with conventional plastic counters of a similar kind.
In a preferred embodiment of the invention, the plastic ring is applied over the whole circumference of the filler piece, within a certain peripheral region; however, it is also possible to surround (radially and/or axially) only parts of the peripheral region of the filler piece with the plastic ring.
The plastic ring is preferably highly resistant to wear and abrasion, and capable of undergoing any desired form of graphic design; it may be made either in the same colour as the filler piece, or in any other desired colour. Alternatively, it can for example be made transparent or translucent, and be provided with lenticular faces. The rim of the plastic ring may be made in a variety of forms, and may be e.g. round, polygonal, or the like. The primary benefit of high abrasion-resistance is the prevention of so-called white fracture at the edges of the plastic ring (phase separation of elastomeric from thermoplatic component), and also on the graphic design itself.
The exposed surface of the plastic ring and/or filler piece may be provided with a mechanical impression, such as a face value, and this can additionally be in the form of an embossed coding e.g. in braille or the like.
To provide security against forgery, security printing processes, and additional pigments, colourings, etc., can also be employed on or in the plastic ring and on or in the filler piece.
Pigments employed may be fluorescent and/or luminescent security elements which can be excited e.g. by ultraviolet radiation, visible light, an electrical field, or even thermal radiation. It is also possible to incorporate glass beads or elements possessing special light-reflecting effects within the plastic ring and/or filler piece, either on their own or in combination with the abovementioned security elements. Holograms may also be provided as a security feature in or on plastic ring and/or filler piece. By placing specially prepared films inside, or on the surface of, the counter, the counter can be personalized, or individually marked in some other way, e.g. by means of a laser.
The plastic ring and/or filler piece can be printed by all known printing processes. Very precise colours and very high colour fidelity, with very strong colour tones, can be obtained. In accordance with the invention a very large display area is available for such printing, including practically the entire surface of the plastic ring and filler piece, and also, if a suitably transparent surface is provided, the interior of the plastic ring and filler piece.
Preferred materials for the plastic ring are injection-mouldable thermoplastics such as polystyrene, polyethylene, polymethyl methacrylate, polyamide, polyoxymethylene, polybutylene glycol terephthalate, cellulose acetate butyrate, polyphenyl siloxane, acrylonitrile butadiene styrene, polycarbonate, or butadiene-styrene block copolymer; or polyurethane etc. The thermoplastic material for the plastic ring can also be thermochromic, e.g. one changing colour at 32xc2x0.
To improve the handling quality of the surface of the plastic ring, at least one suitable other plastic material possessing lower hardness and higher roughness and thus giving the counter a high-quality, attractive xe2x80x9csoft touchxe2x80x9d may additionally be applied to at least parts of the outer region of the plastic ring.
The preferred material for the filler piece is a metal alloy (coin), enabling the counter to be used both at the casino table and in a gaming machine or other slot-machine. The metallic filler piece must therefore be capable of being detected, for example by inductive or capacitive methods.
The metal filler piece has a central impression region on its surface, on which information such as a face value, or any other number, is shown.
As an alternative to the coin as filler piece, a plastic filler piece yielding special effects may be used, but care must be taken to ensure that it is suitable for use in a slot-machine, that is to say, the counter must be detectable e.g. by inductive and/or capacitive methods. A possible way of achieving this is to incorporate fine metal particles 9, suitable for use in slot-machines, within the material of the plastic filler piece, and/or apply such particles to its surface. (See FIG. 4). These metal particles 9 may be magnetic, or may be magnetizable in which case they constitute a detectable security and/or registration mark. The usual size of such metal particles 9, which are also called xe2x80x9ctinselxe2x80x9d, is around 100 xcexcm. It is also possible to apply or incorporate a metallic layer 10 on or in the plastic body of the inserted piece, in which case the laminated plastic filler pieces can be stamped, easily and at low cost, out of sheets of material. (See FIG. 5)
Like the plastic ring, the filler piece is preferably more or less disc-shaped, and the edge or edges can show the same variants as the plastic ring.
Both the plastic ring and the filler piece are preferably made rotationally symmetrical, in their annular form and disc form respectively.
To improve the connection between the plastic ring and the filler piece, e.g. more or less axial extensions can be provided on the plastic ring and/or filler piece which in the overlapping marginal region project from the plastic ring into the filler piece and/or from the filler piece into the plastic ring.
The filler piece is preferably centred in the plastic ring in both axial and radial directions, and so has optimal protection against mechanical damage. This is all the more important because the most significant information is preferably displayed on the filler piece, in a central impression region of its surface.
Furthermore, the stackability of the counters can be improved by providing small ridges and/or grooves extending more or less axially from the surface of the plastic ring. When the counters are stacked on one another, a ridge on one counter will then engage in a groove in the adjacent counter. Alternatively, an axial annular ridge may be provided on the plastic ring on one side of the counter, and another axial annular ridge, but of smaller diameter, on the other side of the counter. These ridges of different diameters then engage in one another when two counters are placed one on top of the other, so that extremely stable, tall stacks can be obtained.
Other notable features of these materials are their good chemical resistance and light fastness, and the pleasing chink of the counters when used as gaming chips.
Choice of counter size includes the 36 and 40 mm diameters of the EU standard, and diameters of 34, 38, 43 and 45 mm are also possible.
The weight that can be obtained, if the selected material is polypropylene with 50% glass or polyamide and polyoxymethylene with approximately 70% barium sulphate added, is about 10 grams.
Owing to the fact that the filler piece extends over the whole area of the plastic part (and is not located only in the central region), considerably greater volume and weight are obtained. This is one of the essential requirements for amusement arcade tokens, which must have a certain minimum weight. With the subject-matter of the present invention this minimum weight can be obtained very easily, as the filler piece extends over practically the entire outer diameter of the token and is not restricted to the central region only.
The subject-matter of the present invention derives not only from the subject-matter of the individual claims but also from the individual claims taken in combination. All details and features disclosed in the documents, including the Abstract, and especially the physical form illustrated in the drawings, are claimed as essential to the invention in so far as they are novel, whether separately or in combination, with respect to the state of the art.
The invention will now be described in detail with reference to drawings illustrating just one way of carrying out the invention. Further features essential to the invention and advantages of the invention will be apparent from the drawings and their description.

Disc-shaped counter in the form of a plastic ring with a filler piece


An anti-stall tool in an oil well drilling assembly that controls reciprocation of the drill bit by a controller that alters weight-on-bit (WOB) depending upon measured downhole pressure or torque. The downhole controller keeps the drill bit rotating by maintaining WOB during normal drilling operations, increasing WOB if sensed working pressure indicates that drill bit loading or torque is undesirably low, and reversing WOB by applying a spring force for retracting the drill bit if excessive working pressure or torque is sensed.

Coiled tubing drilling requires the use of a downhole positive displacement motor (PDM) to rotate the drill bit. During drilling operations, the unloaded PDM rotates at a constant RPM and achieves a "freespin" motor pressure, with respect to the fluid flow rate. As the drill bit encounters the bottom of the hole and force is transferred to the bit, referred to as weight-on-bit (WOB), the motor will sense an increase in torque. The increase in torque is a result of increased resistance to rotating at the constant RPM (assuming a constant flow rate). In turn, the PDM requires additional pressure to turn the motor at the constant RPM while under increased resistance. If the resistance increases to a condition which prohibits the PDM from rotating (i.e. excessive WOB), a motor stall is encountered. During a motor stall, the motor stops turning, the downhole fluid path is severely restricted, and the surface pump pressure dramatically increases. This event can eventually cause a motor failure, which requires the drilling process to be stopped, and the coiled tubing to be fatigue-cycled as the bit is pulled off bottom and run back into the hole to start drilling again.
A downhole tool that monitors motor pressure and sharply reduces the occurrence of motor stalls will increase overall drilling efficiency by:
(1) Increasing the average rate of penetration. This is achieved by reducing the occurrences of pulling off-bottom every time the motor stalls.
(2) Decreasing the damage to PDMs through repeated motor stalls, thereby decreasing occurrence of downhole failure.
(3) Decreasing the fatigue cycles on the coiled tubing. This increases the number of wells a coiled tubing string can service.
By achieving a more efficient drilling operation, the operators can substantially increase the cost savings of drilling a well.
The present invention provides an anti-stall tool that controls WOB during drilling operations, resulting in improved overall drilling efficiency.


Methods and compositions are disclosed utilizing the optically pure (S)-isomer of lomefloxacin to treat bacterial infection. In particular, this compound is a potent drug for the treatment of Mycobacteria infection.

This invention relates to novel compositions of matter containing optically pure (S)-lomefloxacin. These compositions possess potent activity in treating various infections while avoiding adverse effects associated with racemic lomefloxacin including but not limited to headache, stomach discomfort, gastrointestinal disorders, hypoglycemia, renal and hepatic dysfunction, allergic reactions and respiratory distress, and arthropathy, such as cartilage lesions and erosion and abnormalities in bone growth in immature patients. Additionally, these novel compositions of matter containing optically pure (S)-lomefloxacin are useful in treating infection in those patients with impaired renal function. Also disclosed are methods for treating the above-described conditions in a human while avoiding adverse effects that are associated with the racemic mixture of lomefloxacin, by administering the (S)-isomer of lomefloxacin to said human.
Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and 1 or (+) and (xe2x88x92) are employed to designate the sign of rotation of plane-polarized light by the compound, with (xe2x88x92) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric mixture. A 50:50 mixture of enantiomers is referred to as a racemic mixture.
Stereochemical purity is of importance in the field of pharmaceuticals, where 12 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the xcex2-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer.
Furthermore, optical purity is important since certain isomers may actually be deleterious rather than simply inert. FQr example, it has been suggested that the D-enantiomer of thalidomide was a safe and effective sedative when prescribed for the control of morning sickness during pregnancy, and that the corresponding L-enantiomer was a potent teratogen.
Lomefloxacin is described in U.S. Pat. No. 4,528,287 and Japan Patent Publication No. 64979 (1985). Lomefloxacin is currently available commercially in the United States as MAXAQUIN(copyright) as well as in Argentina, Japan, Mexico and certain countries in Asia and Eastern Europe, as the racemic mixture, i.e., it is a 1:1 mixture of optical isomers. It is the optically pure, or substantially optically pure (S)-isomer of lomefloxacin, which is the subject of the present invention, hereinafter referred to as (S)-lomefloxacin.
Racemic lomefloxacin, having the chemical name 1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-lpiperazinyl)-4-oxo-3-quinolinecarboxylic acid, belongs to the quinoline class of antibiotics. The quinoline antibiotics, in general, exhibit a broad spectrum of antibacterial action, demonstrating effectiveness against both Gram-positive and Grain-negative bacterial strains. Quinoline antibiotics have been shown to be effective in treating infections of the respiratory, genito-urinary, and gastrointestinal tracts. They have also demonstrated utility in the treatment of patients with cystic fibrosis and pulmonary infections. Effectiveness has also been demonstrated in the treatment of intra-abdominal, bone and joint, skin, soft-tissue, pelvic, and eye, ear, nose, and throat infections.
Examples of Gram-positive bacteria include but are not limited to Streptococcus, Staphlococcus, Mycobacteria, Listeriaceae, Bacillus and Nocardia. A number of Gram-positive bacteria cause respiratory tract infections including, but not limited to, Streptococcus pneumoniae and Mycobacteria. The majority of clinically diagnosed cases of pneumonia are caused by Streptococcus pneumoniae. However, recently there has been an increase in the number of pneumonias caused by Mycobacteria. Three different species of Mycobacteria, Mycobacteria tuberculosis (M. tuberculosis), Mycobacteria bovis (M. bovis), and Mycobacteria africanum (M. africanum) can cause a disease state commonly known as tuberculosis. Tuberculosis is a highly contagious disease which is most commonly transmitted by aerosolized respiratory secretions. While infection usually begins in the lungs, mycobacteria can easily spread to other organs as well, including eyes, intestine, pericardium, peritoneum, bone and joints, urinary tract, and lymphatic system. See The Merck Manual, 16th ed., pp. 131-146, Merck Sharpe and Dohme.
In addition to M. tuberculosis, M. bovis, and M. africanum, other species of Mycobacteria include M. chelonei, M. Marinum, M. avium and M. kansasii.
The quinoline antibiotics derive their activity through inhibition of the bacterial enzyme, DNA gyrase, which is responsible for catalyzing the bacterial DNA supercoiling necessary to pack DNA filaments into bacterial cells. This inhibition causes irreversible chromosome damage leading to bacterial cell death. The selectivity of quinoline antibiotics for bacterial cells is the result of the supercoiling mechanism in eukariotic cells being mediated by a different set of enzymes not susceptible to quinoline inhibition. Quinoline antibiotics are also thought to interfere with proper bacterial cell membrane function, also contributing to cell death.
The first quinoline antibiotic to be commercialized, nalidixic acid, was discovered following the observation that the structurally similar 6-chloro-1H-ethyl-4-oxoquinolone-3-carboxylic acid, a minor by-product of the commercial production of the antimalarial agent chloroquine, exhibited weak antibacterial action. Since the discovery of nalidixic acid, some 7,000 analogues belonging to approximately 16 different ring systems have been synthesized and tested for antibacterial action. From this data, a comprehensive structure/activity relationship has been elucidated.
Structural activity studies have demonstrated that substitution, at position 1 and a carbonyl substitution at position 4 on the quinoline ring appear to be required for antimicrobial activity. No substitution at position 2 and a carboxyl function at position 3 also appear to be required for activity. The only exception appears to be a thiazolidone ring fused at positions 2 and 3. Depending on modification, the presence of additional fused rings, as well as various ring substitutions can be either beneficial or detrimental to activity.
Racemic lomefloxacin exhibits a broad spectrum of antibacterial action, demonstrating effectiveness against both Gram-positive and Gram-negative bacterial strains. Lomefloxacin has shown to be more effective against Gram-negative bacteria. In particular, lomefloxacin has shown excellent bacteriocidal activity against strains of Enterobacteriaceae, Haemophilus influenzas, Neisseria gonorrhoeae, Branhamella catarrhalis, L. pneumophilia, and good-to-moderate activity against strains of Acinetobacter, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis, but poor activity against Pseudomonas cepacia. There is only a low propensity for bacteria to develop a resistance to lomefloxacin by spontaneous mutation. However, development of resistance is facilitated when bacteria are exposed to sub-inhibitory concentrations of the antibiotic.
Lomefloxacin has an average elimination half-life of approximately 8 hours with peak plasma concentrations occurring at approximately 1 hour after oral dosing in humans. Its long half-life and dose proportionality have lead to introduction of lomefloxacin as the first, once-daily 4-quinoline antibiotic.
Furthermore, unlike ciprofloxacin, lomefloxacin does not interfere with the metabolism of theophylline. Likewise, co-administration of ranitidine with lomefloxacin has no effect on lomefloxacin""s pharmacokinetics. However, coadministration of sucralfate with lomefloxacin, presumably through aluminum complexation, does reduce the absorption of the antibiotic. In patients with reduced renal function, lomefloxacin exhibits reduced renal clearance, with a consequential prolongation of the half-life by up to 24 hours. Antibacterial levels of lomefloxacin are therefore maintained in patients with reduced renal function for up to five days.
Little is known about the pharmacology of the individual isomers of lomefloxacin. The pure enantiomer form of ofloxacin, a related quinoline antibiotic, has been studied (Antimicrob. Agents Chemother., 1988, 32(9), 1336-1340). The (S)-isomer of ofloxacin has been reported to be twice as potent a bactericide as the racemate against a variety of Gram-positive and Gram-negative pathogens.
The racemic mixture of lomefloxacin is presently used primarily as an antibiotic agent for treatment of infection of the upper respiratory and urinary tracts. Viral infections of the respiratory tract are acute illnesses with local and systemic manifestations. Coryza (common cold), pharyngitis, laryngitis (including croup), and tracheobronchitis are common respiratory syndromes. See, for example, Merck Manual 5th Ed., p. 169, Merck, Sharpe and Dohme Research Laboratories (1987). Bacterial infections of the lower urinary tract are very common. The majority of urinary tract infections are caused by Gram-negative bacteria. organisms gaining access to the urethra may colonize on the periurethral glands and produce acute and chronic infection. This condition is termed urethritis. Infections of the prostate gland give rise to the condition prostatitis. Enteric, Gram-negative organisms are the most common cause of prostate infection. Merck Manual 5th Ed., p. 1610, Merck, Sharpe and Dohme Research Laboratories (1987).
Additionally, racemic lomefloxacin has also been used in treating enteritis, sexually transmitted diseases, obstetric and gynecological infections, surgical infections, skin, soft tissue and joint infections, otorhinolaryngologic infections and ophthalmological infections.
Lomefloxacin has been shown to have activity against Mycobacteria tuberculosis, the most common causative agent of the tuberculosis disease. (Piersimoni et al., 1992, xe2x80x9cIn Vitro Activity of the New Quinolone Lomefloxacin against Mycobacterium tuberculosis,xe2x80x9d Am. Rev. Respir. Dis. 146:1445-1447). Piersimoni et al. compared the inhibitory effect of ofloxacin, ciprofloxacin, and lomefloxacin against 79 strains of M. tuberculosis which were susceptible to conventional drug therapy and 11 strains of M. tuberculosis which were resistant to conventional drug therapy. Their data showed that the MIC50 and MIC90 of lomefloxacin in the 79 susceptible strains were, respectively, 0.96 xcexcg/ml and 1.02 xcexcg/ml with a range of 0.5 to 2.0 xcexcg/ml. The MIC50 and MIC90 of lomefloxacin in the 11 resistant strains were, respectively, 1.0 xcexcg/ml and 1.1 xcexcg/ml. Piersomoni et al. concluded that lomefloxacin, orally administered once daily could achieve adequate serum levels to inhibit M. tuberculosis.
Although lomefloxacin and quinoline antibiotics have several advantages, they also have disadvantages, namely, adverse effects. The adverse effects of quinoline antibiotics in general include arthropathy, headache, stomach discomfort, gastrointestinal disorders, hypoglycemia, renal and hepatic dysfunction, allergic reactions and respiratory distress, and central nervous system effects including convulsions, increased intracranial pressure, and toxic psychoses. The adverse effects of lomefloxacin, in particular, include but are not limited to headache, stomach discomfort, gastrointestinal disorders, dizziness, phototoxicity, and arthropathy, such as cartilage lesions and erosion and abnormalities in bone growth in immature patients. Thus, it would be particularly desirable to find a compound with the advantages of the racemic mixture of lomefloxacin which would not have the aforementioned disadvantages.
It has now been discovered that the optically pure (S)-isomer of lomefloxacin is effective in treating infection in a human. Further, it has also been discovered that the optically pure (S)-isomer of lomefloxacin is effective in treating infection in a human while avoiding adverse effects associated with the administration of racemic lomefloxacin, including but not limited to headache, stomach discomfort, gastrointestinal disorders, hypoglycemia, renal and hepatic dysfunction, allergic reactions and respiratory distress, and arthropathy, such as cartilage lesions and erosion and abnormalities in bone growth in immature patients. The present invention also includes methods for treating the above-described conditions in a human while avoiding the adverse effects that are associated with the racemic mixture of lomefloxacin, by administering the optically pure (S)-isomer of lomefloxacin to said human.
The present invention is a method of treating infection in a human which comprises administering to the human, an amount of (S)-lomefloxacin, or a pharmaceutically acceptable thereof, substantially free of its (R)-stereoisomer, said amount being sufficient to alleviate infection.
The present invention encompasses a method of treating infection in a human while avoiding the concomitant liability of adverse effects associated with the administration of racemic lomefloxacin, which comprises administering to said human, an amount of (S)-lomefloxacin, or a pharmaceutically acceptable salt thereof, substantially free of its (R)stereoisomer, said amount being sufficient to alleviate infection, but insufficient to cause said adverse effects associated with administration of racemic lomefloxacin.
The present invention also encompasses an antibiotic composition for treating infection in a human which comprises, an amount of (S)-lomefloxacin or a pharmaceutically acceptable salt thereof, substantially free of its (R)-stereoisomer, said amount being sufficient to alleviate said infection but insufficient to cause adverse effects associated with lomefloxacin.
The available racemic mixture of lomefloxacin (i.e., a 1:1 mixture of the two enantiomers) possesses antibiotic activity, and provides therapy and a reduction of symptoms in a variety of conditions and disorders related to bacterial infection; however, this racemic mixture, while offering the expectation of efficacy, causes adverse effects. Utilizing the substantially optically pure (S)-isomer of lomefloxacin results in clearer dose-related definitions of efficacy, diminished adverse effects, and accordingly, an improved therapeutic index. It is therefore, more desirable to use the (S)-isomer of lomefloxacin.
The term xe2x80x9cadverse effectsxe2x80x9d includes, but is not limited to headache, stomach discomfort, gastrointestinal disorders, hypoglycemia, renal and hepatic dysfunction, allergic reactions, nausea, photosensitivity (phototoxicity), dizziness, diarrhea, respiratory distress, and arthropathy, such as cartilage lesions and erosion and abnormalities in bone growth in immature patients. (See Physician""s Desk Reference, 1994, p. 2216.)
The term xe2x80x9csubstantially free of its (R)-stereoisomerxe2x80x9d as used herein means that the composition contains a greater proportion of the (S)-isomer of lomefloxacin in relation to the (R)-isomer of lomefloxacin. In a preferred embodiment the term xe2x80x9csubstantially free of its (R)-isomerxe2x80x9d as used herein means that the composition contains at least 90% by weight of (S)-lomefloxacin, and 10% by weight or less of (R)-lomefloxacin. These percentages are based on the total amount of lomefloxacin present in the composition. In the most preferred embodiment the term xe2x80x9csubstantially free of the (R)-stereoisomerxe2x80x9d means that the composition contains at least 99% by weight (S)-lomefloxacin, and 1% or less of (R)lomefloxacin. In another preferred embodiment, the term xe2x80x9csubstantially free of its (R)-stereoisomerxe2x80x9d as used herein means that the composition contains 100% by weight of (S)-lomefloxacin. The terms xe2x80x9csubstantially optically pure (S)-isomer of lomefloxacinxe2x80x9d and xe2x80x9coptically pure (S)-isomer of lomefloxacinxe2x80x9d are also encompassed by the above-described amounts.
The term xe2x80x9camount sufficient to alleviate infectionxe2x80x9d as used herein means an amount which eliminates or inhibits the growth of foreign microorganisms that are harmful to the normal functioning of the host organism, particularly humans.
It has unexpectedly been discovered that (S)-lomefloxacin is more active than (R,S)- or (R)-lomefloxacin in inhibiting certain species of Mycobacteria, including but not limited to M. tuberculosis, M. chelonei and M. marinum. It has further been discovered that (S)-lomefloxacin is more active than (R)-lomefloxacin in inhibiting M. avium and M. kansasii.
In a specific embodiment of the present invention, an effective amount of (S)-lomefloxacin is used to treat an individual infected with Mycobacteria; said effective amount being sufficient to reduce the infection. In an preferred embodiment, the Mycobacteria is selected from a group consisting of M. tuberculosis, M. chelonei, M. marinum, M. avium and M. kansasii.
Thus, the present invention encompasses an improved method of treating infection in a human or animal, caused by mycobacteria which comprises administering an effective amount of S-lomefloxacin, substantially free of its R-stereoisomer. In addition, the invention encompasses the treatment of mycobacteria infection in a human by administering an effective amount of S-lomefloxacin, substantially free of its R-stereoisomer alone or in combination with another therapeutic agent, such as an antiviral or another antibiotic. Suitable antivirals or antibiotics are known to those skilled in the art and include but are not limited to AZT, acyclovir, gancyclovir, ribavarin; and penicillin, cephalixm, amikacin, gentamycin, ethanbutil, rifampacin, erythromycin, and tetracycline.
As a result of the increased activity of S-lomefloxacin over that of the racemate or R-lomefloxacin in the treatment of certain bacterial infections, the effective dose may be lower than the doses described herein, e.g., from about 50 mg to 400 mg per day; preferably 50 mg to 200 mg per day. However, the doses described further herein may also be used if desired or necessary for a particular patient.
The chemical synthesis of the racemic mixture of lomefloxacin can be performed by the method described in U.S. Pat. No. 4,528,287. The method involves the reaction of 1,4-dihydro-4oxoquinoline-3-carboxylic acid 2 (where X=Cl or F) with piperazine 1. The preparation of the type 2 compounds has previously been described in Japanese Patent Publication No. 141286/1978, Japanese Patent Publication No. 47658/1980 and Japanese Patent Publication No. 30964/1981.
Furthermore, the (S)-isomer of lomefloxacin may be obtained by resolution of the mixture of enantiomers of lomefloxacin using conventional means such as an optically active resolving acid; see, for example xe2x80x9cStereochemistry of Carbon Compounds,xe2x80x9d by D. L. Eliel (McGraw Hill 1962) and Lochmuller, C. H. et al., J. Chromatogr. 113:(3) 283-302 (1975). (S)-Lomefloxacin can be prepared from the racemate through the diastereomeric crystallization scheme shown below:
Racemic lomefloxacin is treated with an optically pure base (an amine is shown above) to give a pair of diastereomeric salts. The difference in solubility between the two diastereomers allows one to be selectively crystallized from the solvent while the other remains in solution. Crystals of the single diastereomer are then separated from the other diastereomer by filtration. Once separated, the diastereomers can be converted back to the original enantiomers by treatment with acid.
The magnitude of a prophylactic or therapeutic dose of (S)-lomefloxacin in the acute or chronic management of disease will vary with the severity of the condition to be treated and the route of administration. The dose, and perhaps the dose frequency, will also vary according to the age, body weight, and response of the individual patient. In general, the total daily dose ranges, for the conditions described herein, is from about 100 mg to about 400 mg. However, the dosage may be as high as about 800 mg. Preferably, a daily dose range should be between about 100 mg to about 200 mg. In managing the patient, the therapy should be initiated at a lower dose, perhaps about 100 mg to about 200 mg and increased up to about 400 mg or higher depending on the patient""s global response. It is further recommended that children, patients over age 65, and those with impaired renal or hepatic function, initially receive low doses. Those dosages should also be titrated based on global response and blood level. In some cases, it may be necessary to use dosages outside these ranges.
The term, xe2x80x9can amount sufficient to alleviate infection but insufficient to cause said adverse effects,xe2x80x9d is encompassed by the above described dosage amounts and dose frequency schedule.
The term, xe2x80x9cmethod of treating infectionxe2x80x9d as used herein, includes but is not limited to infections such as urinary tract infection, upper and lower respiratory tract infection, sexually transmitted infection, ophthalmological infection, gastrointestinal infections such as those caused by H. pylori and any other infections which may arise in cells or tissues of a human and which require treatment with antibiotics. Such infection may be caused by either Gram-positive or Gram-negative bacteria. The Gram-negative bacteria include but are not limited to Escherichia, Haemophillus, Klebsiella, Proteus, Moraxella, Citrobacter, Enterobacter, Pseudomonas, Salmonella, Shigella, Yersinia, camplobacter, Neisseriaceae and Serratia. The Gram-positive bacteria include but are not limited to Staphlococcus, treptococcus, Bacillus and Mycobacteria.
The present inventors have shown that optically pure (S)-lomefloxacin unexpectedly has an even lower MIC50 and a lower range MIC50 than that for either (R)- or racemic lomefloxacin for Mycobacteria tuberculosis and a lower MIC50 than R-lomefloxacin for Mycobacteria kansasii and Mycobacteria avium. (See infra, Example 6).
Any suitable route of administration may be employed for providing the patient with an effective dosage of (S)-lomefloxacin. For example, oral, rectal, parenteral, transdermal, subcutaneous, intramuscular, and the like may be employed as appropriate. Dosage forms include tablets, coated tablets, troches, dispersions, suspensions, solutions, caplets, capsules, patches, and,the like.
The pharmaceutical compositions of the present invention comprise (S)-lomefloxacin as active ingredient, or a pharmaceutically acceptable salt thereof, and may also contain a pharmaceutically acceptable carrier, and optionally, other therapeutic ingredients. (S)-lomefloxacin hydrochloride is a pharmaceutically acceptable salt of (S)-lomefloxacin. The most preferred pharmaceutically acceptable salt of (S)-lomefloxacin is the monohydrochloride salt.
The term xe2x80x9cpharmaceutically acceptable saltsxe2x80x9d refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases including inorganic acids and bases and organic acids and bases.
Since the compound of the present invention is both basic and acidic, salts may be prepared from pharmaceutically acceptable non-toxic acids or bases including inorganic and organic acids or inorganic and organic bases. Such salts may contain any of the following anions: acetate, benzensulfonate, benzoate, camphorsulfonate, citrate, fumarate, gluconate, hydrobromide, hydrochloride, lactate, maleate, mandelate, mucate, nitrate, pamoate, phosphate, succinate, sulfate, tartrate and the like. Particularly preferred are benzensulfonate, hydrobromate, hydrochloride and sulfate. Such salts may also contain the following cations: aluminum, calcium, lithium, magnesium, potassium, sodium, zinc, benzathine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, and procaine.
The compositions include compositions suitable for oral, rectal and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the nature and severity of the condition being treated. The most preferred route of the present invention is the oral route. The compositions may be conveniently presented in unit dosage form, and prepared by any of the methods well known in the art of pharmacy.
In the case where an oral composition is employed, a suitable dosage range for use is, e.g., from about 100 mg to about 400 mg total daily dose, given as a once daily administration in the morning or in divided doses if required. Preferably, a dose of 400 mg is given as a once daily administration. More preferably, a dose range of between about 100 mg to about 200 mg is given as a once daily administration or in divided doses if required. Patients may be upward titrated from below to within this dose range to a satisfactory control of symptoms.
In practical use, (S)-lomefloxacin can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending on the form of the preparation desired for administration, e.g., oral or parenteral (including intravenous injections or infusions). In preparing the compositions for oral dosage form any of the usual pharmaceutical media may be employed. Usual pharmaceutical media includes, for example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like in the case of oral liquid preparations (such as for example, suspensions, solutions, and elixirs); aerosols; or carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents and the like, in the case of oral solid preparations (such as for example, powders, capsules, and tablets) with the oral solid preparations being preferred over the oral liquid preparations. The most preferred oral solid preparation is tablets.
Because of their ease of administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are employed. If desired, tablets may be coated by standard aqueous or nonaqueous techniques. The parenteral dosage form can consist of a sterile solution of the active ingredient, either in its free or salt form, in physiological buffer or sterile water.
In addition to the common dosage forms set out above, the compounds of the present invention may also be administered by controlled release means and/or delivery devices such as those described in U.S. Pat. Nos.: 3,845,770; 3,916,899; 3,536,809; 3,598,123; 3,630,200; 4,008,719; 4,687,660 and 4,769,207, the disclosures of which are hereby incorporated by reference.
Pharmaceutical compositions of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets, or tablets, or aerosols sprays, each containing a predetermined amount of the active ingredient, as a powder or granules, or as a solution or a suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion, or a water-in oil liquid emulsion. Such compositions may be prepared by any of the methods of pharmacy, but all methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation.
For example, a tablet may be prepared by compression or molding, optionally, with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. Desirably, each tablet contains from about 100 mg to about 200 mg of the active ingredient, and each cachet or capsule contains from about 100 mg to about 200 mg of the active ingredient, (S)-lomefloxacin. Most preferably, the tablet, cachet or capsule contains either one of two dosages, about 100 mg or about 200 mg of the active ingredient.
The invention is further defined by reference to the following examples describing in detail, the preparation of the compound, and the compositions of the present invention. It will be apparent to those skilled in the art, that many modifications, both to materials, and methods, may be practiced without departing from the purpose and interest of this invention.

Methods and compositions for treating infection using optically pure (S)-lomefloxacin


A method is provided for producing double labels (1). Two large labels (7, 9) of different size, each of the labels being detachably applied to respective carriers (11, 13) by their adhesive surfaces (35, 37), are respectively detached from their carriers (11, 13), and are adhered together by their facing adhesive surfaces (35, 37). The two labels (7, 9) are dimensioned in such a way that, for the double label, a free end (5) of the adhesive surface of one label (2) protrudes beyond the other label (3). A device for producing such double labels (1) comprises a dispenser (25) for detaching the labels (7, 9) from their carriers (11, 13) and for assembling the labels and adhering them together. The dispenser (25) has parallel dispensing edges (27, 29). The double label (1) has a fixed element, which can be written or printed on, and a free, flexible element (5) for fixing the double label (1) to an object to be labeled or to another carrier strip. The double label (1) enables high-quality goods, such as jewelry or cosmetic products, to be labeled in a very attractive and careful manner.

This invention relates to a method for producing double labels, in which two labels of unequal size, which are detachably applied by adhesive surfaces to a respective carrier, are put together and adhered to one another. The invention further relates to a device for producing double labels, comprising at least two feed devices for supplying at least one label each to a respective carrier and at least one dispensing device for detaching the labels from the carriers and for putting the labels together and adhering them to one another. The invention likewise relates to a double label produced in accordance with the previously mentioned method, preferably by means of the previously mentioned device, the double label comprising two labels of unequal size, each having an adhesive surface, with the free portion of the adhesive surface of the one label protruding past the other label.
Methods, devices and double labels of the type given above are already known from the prior art. For example, a method for producing self-adhesive double labels is described in German published patent application DE-OS 2 063 483, in which an upper label detachably affixed to a carrier tape is applied to a lower label of equal or smaller size, with the lower label likewise being detachably affixed to a carrier tape. The double label produced in this manner can then be attached to an object, or for the time being it can remain on the carrier tape of the lower label for further use. In the known method the upper and lower labels are detachably applied to a respective carrier tape which is rolled up on an unwinding device so that the labels lie on the inside and which is drawn from the unwinding device by a respective winding device. The upper labels in this case are guided over a deflection edge and brought into position for being dispensed, so that the upper labels can be adhered to the lower labels which are guided along immediately below the deflecting edge and which remain on the carrier tape for the time being.
DE-OS 2 063 483 further discloses a device for producing self-adhesive double labels, comprising an unwinding and a winding device for the lower label carrier tape, as well as an additional unwinding device and an additional winding device for the upper label carrier tape. The device further has two deflection edges, the first of which is provided to detach the upper labels from the carrier tape and the second of which is provided to detach the finished double labels from the carrier tape. The two deflection edges here are arranged one following the other in the feed direction of the carrier tapes.
Finally, self-adhesive double labels have also become known from the prior art according to DE-OS 2 063 483, which labels comprise an upper label and a lower label, the upper label adhering by its adhesive layer to the upper side of the lower label. The upper label here can be provided with an adhesive layer merely within the area of a peripheral strip. Furthermore, the upper label can be designed to be larger than the lower label, so that it partly protrudes past the same. The protruding free portion of the upper label, however, has no adhesive layer, since the upper label in this embodiment is provided with an adhesive layer only within the area of a peripheral strip. Instead, the upper label here is glued to the base label by means of an easily separable adhesive layer, so that the upper label can be easily removed if necessary. The free portion herein facilitates the removal of the upper label. In the known double label, only the adhesive surface of the lower label is used to apply the labels to the objects to be labeled. Thus, the double label according to the prior art has the disadvantage that although it can be securely affixed to the objects to be labeled, there is no secure and inseparable bond between the upper and the lower labels. Furthermore, even though the double label does permit a wide variety of optical effects, it is not so well suited for quality items such as jewelry and cosmetics, since the entire adhesive surface of the lower label adheres to the goods. This is viewed as being unsightly and impractical.
Furthermore, German utility model application DE 297 00 468 U1 discloses a label in which a sticker is adhered to a planar carrier. The sticker herein has a first field on which, for example, the price of the goods to be marked can be printed, and a larger second field, both of which fields have a self-adhesive back. After the sticker is removed from a protective foil the first field is folded along a boundary line between the first and the second fields, and it is stuck by its back onto the back of the second field. The sticker is then adhered to the carrier with the remaining self-adhesive surface of the back of the second field. The printed first field herein remains visible through a window in the carrier. However, this known label can only be fully assembled manually and in a relatively complicated manner, for which reason it cannot be produced in a cost-effective and simple process.
Therefore, it is an object of the present invention to create a method and a device for the simple and inexpensive production of a double label in which a very strong bond exists between the two labels and which is also suitable for marking quality items.
In accordance with the invention the object is accomplished by a method of the type given above, in which the two labels are detached from their respective carriers and are adhered to one another by means of adhesive surfaces facing each other. In this manner a strong and virtually inseparable bond occurs between the two labels. The method of the invention further has the advantage that conventional labels that are detachably applied to respective carriers can be joined to form a sturdy double label. No preparation of special preliminary label stages or modification of existing labels is required here. Adhering two labels of unequal size using the method of the present invention yields a double label having a rigid portion which, for instance, can be written or printed upon. In addition, it can also be applied or adhered by its free, more flexible segment to an object to be labeled or to a carrier tape. Thus, the method can be employed not only in a labeling process, but also in the manufacture of double labels.
In an advantageous embodiment of the method of the present invention it is provided that the labels are detached from the carriers by at least one dispensing device. They are adhered together directly following the dispensing device, and they are subsequently dispensed onto an object to be labeled or onto a further carrier. A method of this type has the advantage that the two individual labels forming the double label can be simultaneously detached from the carriers and combined to form a double label in one step. Thus, the method of the present invention is especially quick and economical. The already finished double label can then either be dispensed directly onto an object to be labeled, or it can be dispensed onto another carrier. In the latter alternative, the result is an independently marketable product which can be provided, for example, to mark prices using hand-held labeling devices.
In a further embodiment of the method according to the present invention it is provided that the carriers are carrier tapes, each of which is drawn from an unwinding roller and is guided over a dispensing edge to detach the labels. In this connection, in a preferred embodiment of the present invention, at least two carrier tapes and at least two unwinding rollers are used. Here, the carrier tape with labels on the inside is drawn from the one unwinding roller and the carrier tape with labels on the outside is drawn from the other unwinding roller. Thus, the carrier tapes run toward each other at the dispensing edge and the labels are put together with adhesive surfaces facing one another. Therefore, the method of the present invention can advantageously be performed through modification of already existing machines or labeling devices. The desired result here can be achieved through the orientation of the labels and the appropriate guiding of the carrier tapes.
Because the carrier tapes run toward each other at the dispensing edge, they are drawn from the dispensing edge parallel and in close proximity to one another. This makes it possible to wind up the two carrier tapes on a common winding roller. In this way the method can be further simplified and, moreover, the necessary equipment can be reduced.
To ensure a strong and uniform adhesion of the labels, in an advantageous embodiment of the invention, it is provided that the labels are guided through between two pressure rollers following the dispensing device.
The method of the invention results in an advantageous double label of the type given above, in which two individual labels are adhered to one another, with the adhesive surfaces facing each other. Thus, the double label of the invention is virtually divided into two areas, in which one area comprises two labels stuck together, while the other area is a free, non-adhered portion of a label of which the adhesive area is available for future use. The area comprised of two labels stuck together is very sturdy and has no adhesive surface on its upper side. This means that this area on the upper side can be written or printed upon. The non-adhered portion is more flexible and serves for attachment to objects to be labeled or to another carrier. The double label according to the invention is particularly suitable for marking quality articles such as jewelry or cosmetics, on which a label attached by its entire surface would seem disturbing and unattractive. The label""s shape here can be selected so that only a slight portion of the entire double label adheres to the object to be labeled, while the double portion is for inscription. In this manner quality goods can be labeled very attractively and sparingly.
In a particularly advantageous embodiment of the invention, it is provided that the one label has a larger adhesive surface than the other label, and it protrudes with its free portion past the other label at one segment of a peripheral area. The remaining adhesive surface of the one label adheres to the adhesive surface of the other label. In this case, the free portion of the one label preferably has a lesser width than the adhered area of the double label, so that the adhered area of the double label basically stands out flag-like in relation to the free label portion applied to the object to be labeled. This results in a particularly attractive form of the double label, so that quality items can also be labeled with a correspondingly high-quality label. To be sure, the purpose of the free portion of the one label is ultimately its attachment to the objects to be labeled. However, it can also be detachably adhered temporarily to a carrier. This permits the labels to be supplied in this form for future use, for instance in a labeling machine.
The object given above is further accomplished by a device of the type given at the beginning, in which the dispensing device has dispensing edges lying parallel and adjacent to one another. This particular embodiment of the dispensing device permits the simultaneous, parallel detachment of the two labels, so that they can be put together and adhered to one another immediately following the two dispensing edges. The removal of the individual labels and their combination to form the finished double label can be accomplished virtually in one step through the arrangement of the dispensing edges. By this means the device according to the invention can also be used, for example, as a hand-held labeling device.
In a preferred embodiment of the device according to the invention it is provided that the feed devices are unwinding rollers and the carriers are carrier tapes. One of the unwinding rollers here serves to accommodate one of the carrier tapes with first labels lying on the inside, and the other unwinding roller is provided to accommodate the other carrier tape with second labels lying on the outside. The unwinding rollers are advantageously arranged in such a manner that the first labels on the one carrier tape are fed to the one dispensing edge, and the second labels on the other carrier tape are fed to the other dispensing edge on mutually opposing sides, so that the labels at the dispensing edges are arranged with their adhesive surfaces facing one another. The different manner in which the carrier tapes provided with labels are wound up and the corresponding arrangement of the unwinding rollers make it possible for the mutual adherence of the labels by their adhesive surfaces to be accomplished with low equipment requirements. Therefore, the device according to the invention can also be produced by simple modification of existing devices or designed as an addition to such devices.
As a particularly advantageous embodiment of the device according to the invention, a common winding roller can be provided to wind up the two carrier tapes from the unwinding rollers. Here it is particularly advantageous, and it is provided in a preferred embodiment, that the winding roller is arranged between the two unwinding rollers. Through this arrangement a very compact design and thus a reduction of the required space is possible. This is of particular advantage if the device according to the invention is designed as a hand-held labeling device. For the device of the invention can be used not only as a labeling device for directly marking objects to be labeled, but also as a machine for the production of double labels, which are applied to a carrier tape and provided for later use. In the second embodiment a third unwinding roller is advantageously provided to accommodate an empty carrier tape. The finished double labels can then be dispensed onto this empty carrier tape, the result being an independently marketable product.
To ensure a strong and uniform adherence of the two labels to form a double label, it is provided in a further embodiment of the device of the invention that at least two pressure rollers are arranged following the dispensing device.

Method and device for producing double labels and corresponding double label