MXPA00004564A - Disinfecting contact lenses with bis(biguanides) and polymeric biguanides - Google Patents

Abstract

The present invention is directed to an ophthalmically safe disinfecting solution for contact lenses comprising a biguanide polymer in combination with a bis(biguanide), and a method of using the composition, in the form of an aqueous solution, for disinfecting and/or preserving contact lenses, especially soft contact lenses. The invention can be used to formulate products having greater convenience and/or benefits compared to traditional disinfecting products for contact lenses and can provide a broader, more potent and faster antimicrobial activity overall.

Description

DISINFECTION OF CONTACT LENSES WITH BIS (BIGUANIDAS) AND POLYMERIC BIGUANIDES Field of the Invention This invention relates to new and improved solutions for the treatment of contact lenses and methods for the treatment of contact lenses with said solutions. Specifically, the present invention is directed to disinfecting systems containing the new combination of two disinfecting agents, namely a bis (biguanide) and a polymeric biguanide. BACKGROUND OF THE INVENTION In general, contact lenses that have wide use fall into three categories: (1) hard lenses formed with materials prepared by polymerization of acrylic esters, such as polymethyl methacrylate (MAPM); (2) rigid gas permeable (RPG) lenses formed with silicone acrylates and fluorosilicone methacrylates, and (3) gel, hydrogel or soft type lenses made with hydrophilic or hydrophobic polymerized o-nols, such as methacrylate 2- hydroxyethyl (MAHE). Hard acrylic lenses are characterized by low water vapor diffusion constants and resistance to the effects of light, oxygen and hydrolysis and absorb only minor amounts of aqueous fluids. Due to the durability of hard contact lenses, along with their tendency not to absorb appreciable amounts of water, the selection of disinfecting agents, cleaning agents or other suitable lens care compounds is relatively non-critical. However, unlike hard lenses, soft-type contact lenses tend to bind and concentrate significantly more fluids, environmental contaminants and water impurities, as well as antimicrobial agents and other active components commonly found in solutions for care of the lenses. In most cases, the low levels of the components in the lens care solutions do not lead to eye tissue irritation when used properly. However, especially due to the inherent binding action of protein deposits on the soft lens materials, some disinfectants and preservatives tend to accumulate on lens surfaces and can concentrate at potentially dangerous levels, such that When they are released, they can cause corneal inflammation and irritation of other ocular tissues. It was found that certain antibacterial agents were compatible with contact lenses and exhibited less binding to the lens surfaces. In one case, it was found that chlorhexidine, a biguanide, binds to the material of soft lenses seven times less than benzalkonium chloride. The presence of oily protein deposits of the tear film on a lens, however, can double the amount of chlorhexidine absorbed on the lens compared to a clean lens. U.S. Pat. No. 4,354,952 discloses very dilute disinfectant and cleansing solutions containing chlorhexidine or its salt in combination with certain amphoteric and nonionic surfactants. These solutions resulted in reducing the amount of binding of chlorhexidine to soft hydrophilic contact lenses. Notwithstanding the reduction in binding achieved by this invention, the use of chlorhexidine did give rise to some market problems. The antimicrobial activity of chlorhexidine may be diminished when used with certain amphoteric surfactants. Moreover, it was said that if they are not used in the proper proportion, the surfactant and the disinfectant will precipitate, unless a non-ionic type surfactant is also used. British Patent 1,432,345 discloses disinfecting compositions for contact lenses containing a polymeric biguanide and a mixed phosphate buffer. The compositions described in this patent, however, have corneal coloration values of 17% or more, much greater than desirable for patient acceptance. U.S. Pat. 4,758,595 to Ogunbiyi et al. Describes that a contact lens solution containing polyaminopropylbiguanide (PAPB), also known as po-lihexamethylenebiguanide (PHMB), has a higher efficiency when combined with a borate buffer. These disinfectant and preservative solutions are especially notorious for their broad spectrum of bactericidal and fungicidal activity at low concentrations, together with very low toxicity when used with soft type contact lenses. U.S. Pat. No. 5,453,435 to Raheja et al., Described a preservative system consisting of a combination of chlorhexidine and polyhexamethylenebiguanide. It was found that this preservative system, used in commercial products for rigid gas-permeable lenses, exhibited a better combination of efficacy and low ocular irritation. Compositions containing PHMB and borate have been commercialized in various products, but at levels of approximately 1 ppm or less, for use in Jolandas contact lenses. In general, it is desirable to have the lowest possible level of a bactericide, while maintaining the desirable level of disinfection efficiency, in order to obtain a generous margin of safety and comfort. Some of the most popular products for lens disinfection are solutions for multiple purposes, which can be used to clean, disinfect and moisten contact lenses, followed by direct insertion (eye placement) without rinsing. Obviously, the ability to use a single solution for the care of contact lenses is an advantage. Said solution, however, must be particularly gentle for the eye, since, as indicated above, part of the solution will be in the lens when it is inserted and will come into contact with the eye. With conventional contact lens cleaners or disinfectants, including multi-purpose solutions, lens wearers typically need to digitally or manually rub contact lenses (typically between a finger and the palm of the hand or between the fingers) during the treatment of the contact lenses. The need for daily "rubbing" of contact lenses adds to the time and effort involved in the daily care of contact lenses. Many contact lens wearers do not like to have to perform such a regimen or consider it an inconvenience. Some users may be negligent in the proper "rub" regime, which can lead to discomfort of contact lenses and other problems. Sometimes, rubbing, if carried out too rigorously, which is particularly likely to occur with users who start contact lenses, can damage the lens. This can be problematic when a spare lens is not immediately available. Solutions for contact lenses qualified as "Chemical Disinfection Solution" do not require rubbing to meet the performance criteria bioci-da (to destroy representative bacteria and fungi) established by the US Food and Drug Administration (FDA). . under the Premarket Notification (510k) Guidance Document For Contact Lens Care Products, May 1, 1997. Conversely, a solution for contact lenses, referred to as a "Chemical Disinfection System", which is not Qualified as a Chemical Disinfection Solution, it requires a rub rate to pass the biocidal performance criteria. Traditionally, ultiuso solutions (used to disinfect and moisten or disinfect, clean and moisten) have been qualified as a Chemical Disinfection System, but not as a Chemical Disinfection Solution. A Chemical Disinfection Solution would, in general, require a more effective or stronger disinfectant than a Chemical Disinfection System. The higher the biocidal effect of a solution, however, the more likely it is that it may exhibit toxic effects or adversely affect the user's comfort of the lens. For example, many very effective bactericides used in other contexts, such as mouthwashes, cosmetics or shampoos, being sufficiently safe for use in such products, would be too toxic for ophthalmic use, especially for use in soft lenses, due to the aforementioned tendency of soft lenses to bind chemicals and sensitization. -dad of eye tissues. Similarly, the concentrations of certain bactericides may need to be within lower limits in solutions for use in soft contact lenses than in other products or in solutions for other types of lenses, especially when such solutions are not cleared from the lens. contact before placing the lens in the eye. It would be desirable to obtain a solution for contact lenses that will simultaneously provide (1) a higher level and / or a broader spectrum of biocidal activity and (2) a low level of toxicity to the eye tissue, so that the solution can to be used to treat a contact lens, so that the lens can then be placed in the eye without rinsing the lens solution. In addition to being interesting to develop, it would be especially desirable to obtain a Chemical Disinfection Solution that could be used for soft contact lenses and that would allow the direct placement of a contact lens in an eye after wetting in the solution and / or rinsing and rewet with the solution. Said product can provide a greater efficiency, giving rise to a greater protection for the user of the lens against the infection caused by microorganisms, while giving maximum convenience. Finally, it would be desirable for the biocidal efficacy of the disinfectant solution to be high enough to achieve effective disinfection, or at least a non-inherently ineffective disinfection, of a contact lens with respect to bacteria and fungi in the event that, for For any reason, the user of the contact lens does not carry out a regime involving mechanical rubbing or the like using the solution for contact lenses. BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to an ophthalmically safe disinfecting solution for contact lenses, consisting of: (a) about 0.10 to about 4.0 ppm of a bis (biguanide) in the form of a dihydrochloride salt, or a corresponding concentration of the same bis (bi-guanide) in the form of the free base or of a different water-soluble salt, whose bis (biguanide) has the following general formula: R ^ NH-C-NH-C-NH- ( CH2) n-NH-C-NH-C-NH-R2 (I) NH NH NH NH or in the form of their water-soluble salts, wherein R1 and R2 are independently selected from the group consisting of branched or unbranched alkyl radicals, alkoxyalkyl or alkylsulfide and n is 4 to 16, and (b) about 0.1 to about 3.0 ppm of a polymeric biguanide having the formula: X 1 - [- Z-NH-C-NH-C-NH-] n Z- X2 (II) II II NH NH where Z is an organic divalent bridging group that can be the same or different along the polymer, n is on average at least 3 and X1 and X2 are independently selected from the groups -NH2 and -NH-C-NH-CN; II NH (c) an effective amount of a buffering agent; and (d) water in an amount of at least about 80% by weight. Preferably, the compositions of the present invention also include one or more surfactants. In one embodiment of the invention, the surfactant is a neutral or non-ionic surfactant. The invention is also directed to a method of disinfecting, or cleaning and disinfecting, a contact lens, consisting of wetting the lens for a given period of time in the aqueous solution described above and then directly placing the lens treated in the user's eye. In one embodiment of this method, a contact lens does not require rubbing with the solution to achieve the necessary disinfection. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a bar graph showing the biocidal efficacy, after 15 minutes, of a solution containing the combination of two disinfecting agents, namely a bis (biguanide) and a polymeric biguanide, against the theoretical sum of the efficacy biocide of independent solutions of each disinfectant agent. The greater efficiency of the combination compared to the theoretical sum is a measure of the synergy of the combination. Specifically, Fig. 1 shows the theoretical log reduction compared to the log real reduction for alexidine and PHMB with respect to C. albicans microorganisms, after 15 minutes of exposure. FIG. 2 is a bar graph showing the biocidal effi ciency, after 30 minutes, of a solution containing the combination of a bis (biguanide) and a biguanide polymer brakes to the theoretical sum of the biocidal efficacy of independent solutions of each disinfectant agent. Specifically, Fig. 2 shows the theoretical log reduction compared to the log real reduction for alexidine and PHMB with respect to C. albicans microorganisms, after 30 minutes of exposure. DETAILED DESCRIPTION OF THE INVENTION As indicated above, the present invention is directed to a composition involving the combined use of a biguanide polymer and a bis (biguanide) and to a method of using the composition, in the form of aqueous solution, to disinfect and / or preserve contact lenses, especially soft contact lenses. This synergistic combination offers maximum convenience, while providing greater efficiency and, therefore, greater protection against microorganisms compared to traditional contact lens disinfectants. The solution according to the present invention provides a broader, more potent and faster overall antimicrobial activity when considering the entire range of microorganisms, based on commonly tested representative bacteria and fungi. In particular, the disinfectant solutions of the present invention are effective at low concentrations against a broad spectrum of microorganisms, including, but not limited to, Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Candi da albicans and Fusarium solani. A disinfectant solution is defined, in general, as a contact lens care product that contains one or more active components (e.g., antimicrobial agents and / or preservatives) in concentrations sufficient to destroy the deleterious microorganisms on the surface of the contact lens. a contact lens within the minimum recommended soaking time. The minimum recommended soaking time is included in the instructions for the use of the disinfectant solution. The term "disinfectant solution" does not exclude the possibility that the solution may also be useful as a preservative solution, or that the disinfectant solution may also be useful for other purposes., such as daily cleaning, rinsing and storage of contact lenses, depending on the particular formulation. The present solution, together with its container or bottle and packaging, which includes instructions for use according to a specified regime, can be considered as a new and improved kit, package or system for the care of contact lenses. By the term "soft lens" reference is made to a lens having a proportion of hydrophilic repeating units such that the water content of the lens during use is at least 20% by weight. The term "soft contact lens", as used herein, refers, in general, to those contact lenses that bend easily under small amounts of force. Typically, soft contact lenses are formulated from polymers having a certain proportion of repeating units derived from hydroxyethyl methacrylate and / or other hydrophilic monomers, typically crosslinked with a crosslinking agent. However, more modern contact lenses are being made from materials containing high Dk silicone. By the term "ophthalmically safe" with respect to a solution for contact lenses it is meant that a contact lens treated with the solution is safe for direct placement in the eye without rinsing, ie, that the solution is safe and comfortable for daily contact with the eye through a contact lens that has been moistened with the solution. An optically-safe solution has a tonicity and pH that are compatible with the eye and contains materials, and quantities thereof, that are non-cytotoxic according to ISO standards and FDA guidelines (Food &; US Drug Administration) Reference is here made to a solution that is useful for cleaning, chemical disinfection, storage and rinsing of a soft contact lens as a "multi-use solution". The multipurpose solutions do not exclude the possibility that some users, for example users particularly sensitive to chemical disinfectants or other chemical agents, may prefer to rinse or wet a contact lens with another solution, for example a sterile saline solution, before insertion of the lens. The term "multi-use solution" also does not exclude the possibility of periodic cleaners not used on a daily basis or supplemental cleaners to remove proteins, for example enzymatic cleaners, which are typically used on a weekly basis. By the term "cleaning" is meant that the solution contains one or more cleaning agents in sufficient concentrations to release and remove poorly bound lens deposits and other contaminants on the surface of a contact lens, especially if used in conjunction with manipulation. digital (for example, manual rubbing of the lens with a solution) or with an accessory device that shakes the solution in contact with the lens, for example a mechanical cleaning aid. The critical concentration of micelles of a surfactant-containing solution is one way of evaluating its cleaning efficiency.

The term "effective multipurpose solution" refers, in an analogous manner, to a solution useful for daily chemical disinfection, storage and rinsing of a contact lens, whose solution does not purport to clean a contact lens, but whose solution still obviates the need for any other solution for daily cleaning, that is, no other solution must necessarily be used together with the solution, or in combination with it, on a daily basis. Although such solutions may contain a surfactant or other agent that can inherently release or prevent deposits of the lens to some extent, such solutions are not necessarily capable of cleaning a contact lens. Effective multipurpose solutions are, therefore, only applicable to lenses used for a limited period of time, either for disposable or frequent replacement lenses. Traditionally, the multipurpose solutions of the market require a regime that involves the mechanical rubbing of the contact lens with the multipurpose solution, in order to obtain the required disinfection. That is to say, that said regime is necessary according to the governmental regulatory authorities (for example, the FDA or Food &Drug Administration in the USA) for a Chemical Disinfection System that is not qualified as Chemical Disinfection Solution. The invention according to the present invention has the advantage that it is possible to formulate a product that, on the one hand, is soft enough to be used as a disinfectant solution and as a wetting agent at the same time and, on the other hand, is capable of achieving a biocidal performance disinfection for a Chemical Disinfection Solution according to the criteria established by the US FDA. for Products for the Care of Contact Lenses (May 1, 1997) that does not require a regime that involves the rubbing of the lenses (even though the rubbing of the lens may offer a greater elimination of microorganisms). In other words, the compositions according to the present invention can be optionally formulated to meet the requirements of the FDA or the ISO Independent Procedure for products for contact lens disinfection. As a result, it is possible to make formulations that offer greater compliance on the part of the patient and greater universal appeal than traditional products for disinfection. or for disinfection and cleaning. It is pointed out that the combination of the biguanide polymer and the bis (biguanide) provides greater efficacy, while not causing irritation or discomfort in the eye, this being an important and provocative concern in the technique of contact lens care. Therefore, greater amounts of the biguanide polymer, by itself, to achieve the same efficacy as the combination would result in greater eye irritation. Specifically, it has been found that greater amounts of biguanide polymer, by itself, to achieve the necessary Ain for a Chemical Disinfection Solution would result in unacceptable ocular irritation, even if a rub regime is recommended. using the solutions of the present invention, the increased biocidal activity can provide greater protection against infection, especially if the rubbing by the contact lens wearer is inadequate or omitted due to negligence or for ignoring the instructions of the According to the present invention, the bis (biguanide) germicides used in the present invention include compounds, and their water-soluble salts, having the following formula: ## STR3 ## CH2) n-NH-C-NH-C-NE-R2 • (I) || | i | I NH NH NH NH where R1 and R2 are independently selected (ie, the same or different) from the group consisting of branched alkyl or unbranched of 4-12, preferably 6-10, carbon atoms; an alkoxyalkyl radical (ie, ether) or alkylsulfide (thioether or dialkylsulfide) of 4-12, preferably 6-10, carbon atoms; or a cycloalkyl or cycloalkylalkyl radical of 5-12, preferably 7-10, carbon atoms; and n is 4 to 16, preferably 6 to 10. By the term "cycloalkyl", whether in cycloalkyl or cycloalkylalkyl, it is meant unsubstituted or substituted cycloalkyl, wherein the substituents are one or more alkyl, alkoxy (-OR) groups or alkylthio (-SR) of 1-6 carbon atoms. In the present disinfectant solution, the biguanides of Formula (I) are suitably used in a total amount of 0.1 to 4.0 ppm, preferably 1.0 to 3.0 ppm, in base to the total aqueous solution. More preferably, bis (biguanides) are used in an amount of 1.5 to 2.5, more preferably approximately 2.0, ppm. The concentration of bis (biguanide) in the solution is directly related to its bactericidal efficacy. The term "ppm" refers to "parts per million" and 1.0 ppm corresponds to 0.0001 weight percent. It is based on the total weight of the composition or, in this case, the total weight of the aqueous disinfectant solution. In the present application, the amount of the bis (biguanide) or other components in a solution according to the present invention refers to the amount formulated and introduced into the solution at the time the solution is prepared. In the course of time (for example, over a storage period of 18 months), the amount of bis (biguanide) in solution can be reduced to some extent. Preferably, the bis (biguani-da) compounds have the above Formula (I), wherein R1 and R2 are independently selected from the group consisting of a branched or unbranched alkyl, alkoxyalkyl (i.e., ether) or alkylsulfide (thioether) radical. and n is 5 to 7. Each of R1 and R2 in Formula (I) above may be, for example, a n-butyl, isobutyl, sec-butyl, tere-butyl, pentyl, neopentyl, octyl, 2-ethylhexyl radical. , dodecyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentyl ethyl or cyclohexylmethyl. Preferred are 2-ethylhexyl (alexidine), 1,5-dimethylhexyl, 1-methylhexyl, 1,3-dimethylpentyl, 1,4-dimethylpentyl, cyclohexylmethyl, 2-norbornyl, propyl-oxyoctyl and propyloxybutyl. The acid addition salts of the invention can be derived from an inorganic or organic acid. In most circumstances, it is preferable that the salts derive from an acid that is readily soluble in water and that gives rise to an anion that is suitable for human use, for example a pharmaceutically acceptable anion. Examples of such acids are hydrochloric, hydrobromic, phosphoric, sulfuric, acetic, D-gluconic, 2-pyrrolidino-5-carboxylic, methanesulfonic, carbonic, lactic and glutamic acids. The hydrochloride salt is preferred. The bis (biguanides) of Formula (I) have relatively hydrophobic end groups. Preferably, the Log P of the compounds is 5 to 10, more preferably 6 to 8, where P is the partition coefficient of the free base, using the following equation, where C is the molar concentration of the bis (biguanide) in each phase is already the degree of ionization of bis (biguanide): octanol p = Ctampon (1-CC) To obtain the partition coefficient of a bis (biguanide), the compound is distributed between a 0.05 M phosphate buffer (pH 11) saturated with octanol and octanol saturated with phosphate buffer after shaking gently at room temperature (26 ° C). The volume ratio of these two phases and the amount of sample are chosen in such a way that the absorbance of the sample of the buffered layer after the distribution has a value between 0.2 and 0.9, using a 1 cm cell and buffer solution as white. Working at a fixed pH and knowing or calculating the pKa, one can determine the value of P using the formula above. See "Quantitative Structure-Activity Relationships for Bigua-nides, Carbamidates and Bisbiguanides as Inhibitors of Streptococcus mutans No. 6715", Warner, V. and Lynch, DJ Med. Chem., 1979, Vol. 22, No. 4, at 359 , 365; and Albert and Serjeant, E., "Determination of Ionization and Stability Constants", Butler and Tanner Ltd., London, England, 1962, both references incorporated herein by reference. Particularly preferred bis (biguanide) compounds of this invention are 2- (decylthiomethyl) pentane-1,5-bis (5-isopropylbiguanide), 2- (decylthiomethyl) pentane-1,5-bis (5,5-diethylbiguanide) and hexane. -1,6-bis (2-ethylhexylbiguanide), the latter also known as alexidine or 1,1'-hexamethylenebis (5- (2-ethylhexyl) biguanide) dihydrochloride. Other preferred bis (biguanides) include 1,1'-hexamethylenebis (5-heptylbiguanide) dihydrochloride, 1,1'-hexamethylenebis (5-octylbiguanide) dihydrochloride and 1,1'-hexamethylenebis (5-hexylbiguanide) dihydrochloride. The biguanide compounds of Formula (I) can be prepared by reaction of a biscyanoguanidine of formula: NH-NH-C-NH-A-NH-C-NH-CN (vi; NH NH with an amine R1NH2 or with two different amines R ^ -N ^ and R2NH2, in the form of an acid addition salt of the same, where R1 and R2 have the meanings given above, at a temperature of 100 ° C to 170 ° C, and A is an alkylene group having the necessary number of carbon atoms.A preferred amine salt is hydrochloride Most diamines are marketed by a variety of sources.The reagents are heated together until the reaction is completed.The reaction proceeds more quickly at higher temperatures, but, if thermal stability is a problem, the reaction would have to The reactants are more conveniently fused together in the absence of solvent, but, if desired, an inert solvent, such as DMSO, 2-methoxyethanol, can be used. 2-ethoxyethanol, nitrobenzene, sulfolane, isopropanol, n-butanol, ether ethylene glycol dimethyl or water, or a mixture of said solvents. The biscyanoguanidine of Formula (VI) can be manufactured from known starting materials, such as hexamethylenedinitrile, which is reduced, for example, with hydrogen and Raney nickel or with borane in dimethyl sulfide to the corresponding diamine (VIII) and the diamine in the form of the acid addition salt, conveniently the dihydrochloride, reacts with sodium dicyanamide or another suitable salt to form the required starting material (VI), as depicted below. NC-A-CN? NH2-A-NH2 '(VII) (VIII) VIII + 2-MN (CN) 2? NC-NH-C-NH-A-NH-C-NH-CN II II NH NH where M is sodium, potassium, zinc or other suitable metal. The sodium salt can be acquired commercially.

The compounds of the present invention can also be prepared by reacting a diamine of Formula (VIII) in the form of an acid addition salt with a cyanoguanidine of the formula: R ^ N-C-NH-CN (IX) II NH or with a cyanoguanidine of Formula (IX) and a cyanoguanidine of the formula: RZHN-C-NH-CN (X) II NH where R1 and R2 have the meanings given above, at a temperature of 100 ° to 170 ° C. A suitable salt of the diamine is, for example, the dihydrochloride. The reagents are heated together until the reaction is complete. The reaction proceeds more rapidly at a higher temperature, but, if thermal stability is a problem, the reaction would have to be carried out at a lower temperature for a longer period of time. If a melt can be formed at these temperatures, the reactants are conveniently melted together in the absence of solvent. If not, or alternatively, the reagents are heated together in a suitable inert solvent, for example those mentioned above. The acid addition salts of the invention are obtained by conventional means. The cyanoguanidines of the formulas (IX) and (X), which can be used as starting materials in the above process, can be obtained by reaction of dicyanamide sodium with an appropriate amine R1NH2 or R2NH2, in the form of acid addition salt , conveniently the dihydrochloride, in a suitable inert solvent. For example, bis (biguanide) known as alexidine is produced from the following sequence of reactions. • 2 C1 • Na * • ß N HjN- (CH2) < r- NH3 + 2 NC CN (XI) (xp > NC- NH- C- NH- (CH2) 6- H- C- NH- NH NH NH (XIII) (XIV) (XV) Compound (XI) is hexamethylenediamine dihydrochloride (MW 189), Compound (XII) is sodium dicyanamide, Compound XIII is HMBDA, hexamethylenebis (cyanoguanide), Compound (XIV) is 2-ethylhexylamine hydrochloride (MW 165.7 ) and Compound (XV) is alexidine dihydrochloride, also known as 1, 6-bis (2-ethylhexylbiguanido) hexane dihydrochloride, also known as hexane-1,6-bis (2-ethylhexylbiguanide) dihydrochloride. This compound has a molecular weight in g / mol (MW) of 581.7 and empirical formula C26H56 10-2HCI. Compound (XV) is commercialized by several sources, including Sigma Chemical Co. (St. Louis, Missouri). Methods for synthesizing the compounds of the present invention are also described in European Patent Application Publication No. 0 125 092 (published on 14.11.84); Rose, F.L. and Swain, G., "Bisdiguanide Having Antibacterial Activity", J. Chem. Soc., p. 4422-4425 (1956), and Warner, Victor D. and Lynch, Donald, "Quantitative Structu-re-Activity Relationships of Biguanide, Carbamidates and Bisdiguanides as Inhibitors of Streptococcus mutans No. 6715", J. Med. Chem., Vol. 22, No. 6, p. 359-366 (1979). The bis (biguanides) of the present invention (Formula I) can be used in combination with one or more polymeric biguanides and water-soluble salts thereof, having the following formula: X 1 - [- Z-NH-C-NH-C -NH-] nZ-X2 (IV) II II NH NH where Z is an organic divalent bridging group which may be the same or different along the polymer, n is on average 3, preferably on average 5 to 20, and X1 and X2 are independently selected from the groups -NH2 and -NH -C-NH-CN. A preferred group of water-soluble NH polymer biguanides will have number average molecular weights of at least 1,000 and, more preferably, will have number average molecular weights of from 1,000 to 50,000. Suitable water-soluble salts of the free bases include, but are not limited to, the hydrochloride, borate, acetate, gluconate, sulfonate, tartrate and citrate salts. The biguanides discussed above and the methods of preparation are described in the literature. For example, U.S. Pat. No. 3,428,576 describes the preparation of polymeric biguanides from a diamine and salts thereof and a diamine salt of dicyanimide. The polymeric biguanides, in combination with the bisbiguanides of the present invention, are effective in concentrations of up to only 0.00001 weight percent (0.1 ppm). It has also been found that the bactericidal activity of the solutions can be increased or that the spectrum of activity can be extended by the use of a combination of said polymeric biguanides with the compounds of the Formula (I) above. The effective amount of the polymeric biguanides (regardless of the particular salt form or if the free base is used) can be a total of only about 0.000010 weight percent (0.10 ppm) and up to about 0.00030 weight percent (3.0 ppm) in the present invention, either in the form of water-soluble or free-base salt. Preferably, the total amount of polymeric biguanide, in combination with the total amount of compounds of Formula (I) above is from about 0.3 to 2.0 ppm, more preferably about 0.4 to 1.0, more preferably about 0.5 to 0.8, ppm. Most preferred are polymeric hexamethylene biguanides, marketed, for example, as the hydrochloride salt by Zeneca (Wilmington, DE) under the trademark Cosmocil ™ CQ. Reference is made to said water-soluble polymers and salts such as polyhexamethylene- (PHMB) or polyamino-nopropylbiguanide (PAPB). The term PHMB or PAPB, as used herein, is intended to include one or more biguanides having the following formula: X1- (CH2) 3- [- (CH2) 3-NH-C-NH-C-NH- (CH2 ) 3-] n- (CH2) 3 ~ X '(V) NH NH where X1 and X2 are as defined above and n is from 1 to 500. Depending on the way in which the biguanides are prepared, the predominant compound that enters within the above formula you can have different groups X1 and X2 or the same groups, with smaller amounts of other compounds within the formula. Such compounds are known and described in U.S. Pat. No. 4,758,595 and British Patent 1,432,345, the patents of which are hereby incorporated by reference. Preferably, the water-soluble salts are compounds in which n has an average value of 2 to 15, more preferably 3 to 12. Additional disinfectant / germicidal components may be employed in the present invention to enhance, complement or further expand the microbicidal activity spectrum of the invention. This includes microbicide-effective amounts of germicides that are compatible with the solution and do not precipitate therein, in concentrations in a range of about 0.000001 to about 0.5 weight percent, depending on the disinfecting agent. particular, as will be appreciated by the person skilled in the art. Suitable complementary germicidal agents include, but are not limited to, thimerosol, sorbic acid, alkyltriethanolamines, phenylmercuric salts, quaternary ammonium compounds and polyquaternium copolymers and mixtures thereof. Suitable salts are soluble in water at room temperature to the point of at least 0.5 weight percent. These salts include gluconate, isethionate, (2-hydroxyethanesulfonate), formate, acetate, glutamate, suc-cinate, monodiglycolate, methanesulfonate, lactate, isobutyrate and glucoheptonate. Representative examples of the quaternary ammonium compounds are compositions consisting of balanced mixtures of n-alkyldimethylbenzylammonium chlorides. An example of a polyquaternium polymer used in ophthalmic applications includes Polyqua-ternium 1® (chemical registration number 75345-27-6), from Onyx Corporation. The present solution optionally contains at least one surfactant. Suitable surfactants may be amphoteric, cationic, anionic or non-ionic, which may be present (individually or in combination) in amounts of up to 15 percent, preferably up to 5 percent, by weight of the composition or solution. Preferred surfactants are amphoteric or nonionic surfactants, which, when used, impart cleaning and conditioning properties. The surfactant must be soluble in the solution for the care of the lens and non-irritating to the tissues of the eye. Many nonionic surfactants contain one or more chains or polymeric components that have repeating oxyalkylene units (-0-R-), where R has from 2 to 6 carbon atoms. Preferred non-ionic surfactants consist of block polymers of two or more different types of repeating oxyalkylene units, whose ratio of different repeating units determines the EHL of the surfactant. Suitable nonionic surfactants include polyethylene glycol esters of fatty acids, for example coconut, polysorbate, polyoxyethylene or polyoxypropylene ethers of higher alkanes (C 2 -C 8). Examples of the preferred class include polysorbate 20 (available under the trademark Tween® 20), polyoxyethylene (23) lauryl ether (Brij® 35), polyoxyethylene stearate (40) (Myrj® 52) and polyoxyethylene stearate (25). ) propylene glycol (Atlas® G 2612). A particular non-ionic surfactant, consisting of a poly (oxypropylene) -poly (oxyethylene) ethylene diamine adduct, having a molecular weight of from about 7,500 to about 27,000, wherein at least 40 weight percent of said adduct is poly (oxyethylene), has been found to be particularly advantageous for use in cleaning and conditioning both soft and hard contact lenses when used in amounts of about 0.01 to about 15 weight percent. The name adopted by the CTFA Cosmetic Ingredient Dictionary for this group of surfactants is poloxamine. Said surfactants can be purchased from BASF Wyandotte Corp., Wyandot-te, Michigan, under the trademark "Tetronic". An analogous series of surfactants, suitable for use in the present invention, is the series of poloxamers, which are poly (oxyethylene) -poly (oxypropylene) block copolymers available under the trademark "Pluronic" (marketed by BASF) . Various other ionic, as well as amphoteric and anionic surfactants, suitable for use in the invention can be easily determined, in view of the above description, by McCutcheon's Detergents and Emulsifiers, North American Edition, McCutcheon Division, MC Publishing Co., Glen Rock, NJ 07452 and the CTFA International Cosmetic Ingredient Handbook, published by The Cosmetic, Toiletry and Fragrance Association, Washington, DC Suitable amphoteric surfactants for use in a composition according to the present invention include materials of the type commercially offered under the trademark "Miranol". An example of another useful class of amphoteric surfactants is cocoamidopropylbetaine, marketed by various sources. The above surfactants, when employed with a buffer enhancer, will generally be present in an amount of 0.01 to 5.0 percent (w / w), preferably 0.1 to 5.0 percent. Typically, the aqueous solutions of the present invention for the treatment of contact lenses are also adjusted with tonicity agents to approximate the osmotic pressure of normal lacrimal fluids., which is equivalent to a 0.9 percent solution of sodium chloride or a 2.5 percent solution of glycerol. Solutions are made to be substantially isotonic with physiological saline alone or in combination; otherwise, if they are simply mixed with sterile water and become hypotonic or hypertonic, the lenses will lose their desirable optical parameters. Correspondingly, excess saline can result in the formation of a hypertonic solution, which will produce stinging and eye irritation. The pH of the present solutions should be maintained in the range of 5.0 to 8.0, more preferably of about 6.0 to 8.0, more preferably of about 6.5 to 7.8; suitable buffers may be added, such as boric acid, sodium borate, potassium citrate, citric acid, sodium bicarbonate, TRIS and various mixed phosphate buffers (including combinations of Na2HP04, NaH2P04 and KH2P0) and mixtures thereof. Borate buffers are preferred, particularly to increase the effectiveness of the biguanides. In general, buffers will be used in amounts ranging from about 0.05 to 2.5 percent by weight and, preferably, between 0.1 and 1.5 percent. The disinfectant / preservative solutions of this invention preferably contain a borate buffer system, which contains one or more of boric acid, sodium borate, potassium tetraborate, potassium metaborate or mixtures thereof. In addition to buffering agents, in some cases it may be desirable to include sequestering agents in the present solutions in order to bind metal ions that could otherwise react with the lens and / or protein deposits and accumulate in the lens. Ethylenediamine tetraacetic acid ("EDTA") and its salts (disodium) are preferred examples. They are usually added in amounts ranging from about 0.01 to about 0.2 weight percent. Other suitable sequestering agents include gluconic acid, citric acid, tartaric acid and its salts, for example sodium salts. Preferred sequestering agents, which are also effective to remove protein deposits, are the phosphonate compounds described in WO 97/31659. The aqueous solutions of the present invention are especially useful for soft contact lenses, with or without further additives. However, the solutions of the present invention can be formulated in specific products for the care of contact lenses, such as wetting solutions, soaking solutions, cleaning and conditioning solutions, as well as solutions for the care of lenses of multipurpose type, etc. and its mixtures. Finally, said solutions can be applied to the lenses outside the eye or while still in the eye, for example in the form of droplets. It may also be desirable to include water-soluble viscosity builders in the solutions of the present invention. Due to their demulcent effect, viscosity increasers have a tendency to increase comfort for the wearer of the lens by means of a film on the surface of the lens that dampens the impact against the eye. Included among the water-soluble viscosity builders are cellulose polymers such as hydroxyethyl- or hydroxyprotectulose, i. car'-ox.- t? e * tilcellulose, povidone, poly.-__-nyl alcohol and the like. Said viscosity builders may be employed in amounts in the range of about 0.01 to about 4.0 weight percent or less. The present solutions may also include eventual demulcents. The aqueous solutions according to the present invention can be used effectively in the disinfection of contact lenses by any of the well-recognized methods. The lenses can be treated by the "cold" soaking method at temperaturr. "environment during a period that goes from approximately 5 canutos to" aprcrimadamente 12 horas. The lenses are then removed from the solution, rinsed with the same or a different solution, for example a preserved isotonic saline solution, and then re-placed in the eye. As previously indicated, contact lens wearers usually need to rub with their fingers or hands contact lenses (typically, between a finger and the palm or between the fingers) during the daily cleaning and / or disinfection of contact lenses. In an embodiment of the present invention, a method is provided in which i is not required. ar during cl-treatment with the specified solution • claimed / 'entr: the removal of the eye and the repositioning of' the lens after the care of the lens. In a preferred embodiment of said method, a soft lens is disinfected, or disinfected and cleaned, with a multipurpose solution or an effective multipurpose solution, which is the only daily solution necessary to treat the lens outside the eye. Thus, in one embodiment of a method according to the invention, the described solution is used to treat a contact lens without rubbing, by a method consisting of: (a) soaking the contact lens that has not been rubbed with the solution for a specified period of time and (b) directly placing the contact lens in the user's eye. Typically, step (a) may involve immersing the contact lens in the solution. The soaking may eventually consist of shaking or similarly stirring a solution container by manual means. Preferably, step (a) involves a period of soaking the contact lens in a container in which the contact lens is completely submerged in the solution. By the term "direct placement" it is meant here to say that the solution is not diluted or rinsed from the lens with a different solution for contact lenses before the "insertion" or placement in the eye. In a particularly preferred embodiment, the method utilizes a multi-use solution that does not require rubbing or effective multipurpose solution, where no other solution or product is required for daily cleaning of the lens, with the possible exception of an enzymatic cleaner. In yet another embodiment of a method according to the present invention, the claimed solution is used to clean a soft lens which is a frequent replacement lens (FRF), planned to be replaced after no more than about three months of use in the eye , or planned to be replaced after no more than about 30 9 days of use in the eye, or planned to be replaced after no more than about two weeks in the eye. Preferably, the lens is made of a polymer consisting of about 0.0 to 5 mole percent of repeating units derived from methacrylic acid (AMA), 10 to 99 mole percent of repeating units derived from hydroxyethyl methacrylate and about 0.5 to 5 mole percent of crosslinking repeating units. The crosslinking repeating units can derive, for example, from monomers such as ethylene glycol dimethacrylate, divinylbenzene and trimethylolpropane trimetacrylate. The following Examples illustrate the compositions and methods of the present invention. EXAMPLE 1 This Example illustrates the preparation of 1,6-bis (cyanoguanidino) hexane, used as a starting material for the bis (biguanides) of the present invention. In the amount of 35.80 g (0.402 mole), dicyanamide sodium (NaC2N3) was suspended in 400 ml of 1-butanol. Then, 23.60 g (0.204 mol) of 1,6-hexanediamine, as well as 33.0 ml of concentrated aqueous hydrochloric acid (0.400 mol) were added. A milky white precipitate appeared immediately, which was probably amine hydrochloride. The mixture was then refluxed for 3.5 h. The suspension was then cooled to room temperature and filtered. The white solid was then washed well with distilled water before drying in vacuo. Yield 46.38 g; C 10 H 18 N 8; calculated: C 48.0%, H 7.20%, N 44.80%; found: C 47.7%, H 7.40%, N 45.12%. 300 MHz X NMR (d6-DMSO) 6.60 ppm (6p, broad m), 2.93 ppm (4p,), 1.34 ppm (4p, broad), 1.15 ppm (4p, broad) . IR (KBr pill, c "1) 3142 (), 2943, 2912, 2862 (w), 2179 (s), 1658, 1609 (s) EXAMPLE 2 This Example illustrates the preparation of the bis (biguanide) known as alexidine for use in the pre-sentate invention Hexamethylenebis (cyanoguanide), in an amount of 1.003 g (0.004498 moles), was placed in a flask, and 1.474 ml (1.163 g, 0.008996 moles) were added thereto. 2-ethylhexylamine 0.74 ml (0.008996 mole) of concentrated HCl was then added The mixture was heated in a flask to remove H20 by boiling After the H20 had disappeared, the temperature of the melt had risen at 195 ° C. The temperature was reduced to 150-160 ° C. and maintained for one hour.The material was cooled to room temperature.The solid can be dissolved in hot water and allowed to crystallize.Example 3 This Example illustrates the preparation of poly (hexamethylenebiguanide), which is also referred to as PAPB or PHMB, for use in combination with bis (big uanidas) in the present invention. In 500 ml of distilled water, 25.08 g (0.100 moles) of 1,6-bis (cyanoguanidine) hexane and 18.99 g (0.100 moles) of 1,6-hexanediamine dihydrochloride were suspended. The pH of this mixture was then brought to 6.8 with dilute hydrochloric acid. The water was then removed by distillation under reduced pressure. The white solid was then transferred to a three-necked flask equipped with a mechanical stirrer and a heating jacket. The intimate mixture of solids was then placed under nitrogen and the temperature of the mixture was raised to 150-155 ° C. The molten reaction mixture had the consistency of honey. The mixture was stirred at 150-155 ° C for 1-1.5 hours before cooling to room temperature. Poly (hexamethylenebiguanide) is obtained as a glassy solid. The yield is essentially quantitative. Melting range 105-125 ° C. 300 MHz X NMR (D20) 3.13 ppm (21, lp, broad t), 2.93 ppm (2p, t), 1.49 ppm (21, Ip, broad s), 1.28 ppm (21, lp, s broad). IR (KBr pellet, cm "1) 3325, 3201 (s), 2931, 2858 (m), 2175 (mw), 1631, 1589, 1550 (s) EXAMPLE 4 This Example illustrates the preparation of an aqueous disinfectant solution according to the present invention consisting of a combination of alexidine and polyhexamethylenebigua-nide (also referred to as PHMB) The following components are used, in the percent by weight indicated by total volume of the solution: ** Molecular Weight 14,500, Tetronic® 1107, an adduct of poly (oxypropylene) -poly (oxyethylene-not) block copolymer of ethylenediamine, a trademark of BASF Wyandotte Corp., Wyandotte, MI. The solution is prepared by gradually heating 80 percent of the water to 80 ° C, while disodium EDTA dissolves therein. Boric acid and sodium borate are added to the heated disodium EDTA solution and dissolved. The sodium chloride is then added to the solution and dissolved, followed by the addition of the surfactant. The solution is sterilized by autoclaving at 120 ° C for 45 minutes. After cooling the solution to room temperature, the bis (biguanide) alexidine and the PHMB are added as a solution through a sterile filter, followed by the rest of the distilled water. The solution is packaged in sterilized plastic containers. EXAMPLE 5 This Example illustrates the best antimicrobial efficacy of the combination of alexidine with polyhexamethylenebiguanide (PHMB) in an aqueous disinfectant solution for contact lenses. The antimicrobial efficacy of each of several compositions for the chemical disinfection of contact lenses was evaluated. Microbial inocula were prepared using Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Serratia marcescens (ATCC 13880), Candida albicans (ATCC 10231) and Fusarium solani (ATCC 36031). The test organisms were cultured on appropriate agar and the cultures were harvested using DPBST ("Dulbecco Phosphate Buffered Saline plus a 0.05% w / v polysorbate 80) sterile or a suitable diluent and transferred to a suitable vessel. The spore suspensions were filtered through sterile glass wool to remove the hyphal fragments, Serratia marcescens was filtered, as appropriate (for example, through a 1.2 μ filter) to clear the suspension. of the collection, the suspension was centrifuged at no more than 5,000 xg for a maximum of 30 minutes at 20-25 ° C. The supernatant was poured and resuspended in DPBST or another suitable diluent.The suspension was centrifuged a second time and the resuspended in DPBST or other suitable diluent.All inoculum suspensions of bacterial and fungal cells were adjusted with DPBST or other suitable diluent at 1 x 107-108 cfu / ml. appropriate cell ion by measuring the turbidity of the suspension, for example using a spectrophotometer at a preselected wavelength, for example 490 nm. A tube containing a minimum of 10 ml of test solution per inoculum organism was prepared. Each tube of the test solution was inoculated with a suspension of the test organism sufficient to give a final count of 1.0 x 10 5 10 cfu / ml, the volume of the inoculum not exceeding 1% of the volume of the sample. The dispersion of the inoculum was assured by vortexing the sample for at least 15 seconds. The inoculated product was stored at 10-25 ° C. Aliquots were taken in the amount of 1.0 ml of the inoculated product for the determination of viable counts after certain periods of time of disinfection. The time points for the bacteria were, for example, 1, 2, 3 and 4 hours when the soaking time of the proposed regimen was 4 hours. The yeasts and molds were studied at an additional time point of > 16 hours (4 times the time of the regime). The suspension was mixed well by vigorous vortexing for at least 5 seconds. The aliquots of 1.0 ml withdrawals were subjected to the specified time intervals to an appropriate series of decimal dilutions in validated neutralizing media. The suspensions were mixed vigorously and incubated for a suitable period of time to allow neutralization of the microbial agent. The viable count of organisms was determined in appropriate dilutions by preparation of triplicate plates of agar "trypticase" I am "(" TSA ") for bacteria and Sabouraud dextrose agar (" SDA ") for molds and yeasts.The bacterial recovery plates were incubated at 30-35 ° C for 2-4 days.The yeasts were incubated at 20- 30 ° C for 2-4 days and mold recovery plates at 20-25 ° C for 3-7 days The average number of colony forming units in the countable plates was determined. 300 ufe / plate for bacteria and yeasts and 8 to 80 ufe / plate for molds, except when the colonies are observed only for the plates of the 10 ° or 10"dilution.1 The microbial reduction was then calculated at specified time points In order to demonstrate the adequacy of the medium used for the growth of the test organisms and to obtain an estimate of the initial inoculum concentration, inoculum controls were made by dispersing an identical aliquot of the inoculum in a suitable diluent, for example DPBST, using the same volume of diluent used to suspend the organism as indicated above. of inoculation in a validated neutralizing broth and incubation for an appropriate period of time, the inoculum control should be 1.0 x 105 - 1.0 x 106 cfu / ml The solutions were evaluated based on the requirement of performance referred to as "Independent Procedure for Disinfectant Products" (which will be referred to hereinafter as the "test to independent ") and is based on the Disinfection Efficacy Test for contact lens care products under the Premarket Notification '(510 (k)) Guidance Document For Contact Lens Care Products, dated May 1, 1997, prepared by the US Food and Drug Administration, Division of Ophthalmic Devices. This performance requirement is comparable to the ISO standard for contact lens disinfection (revised in 1995). The independent test inoculates a disinfectant product with a standard inoculum from a representative range of microorganisms and establishes the degree of viability loss at predetermined time intervals comparable to those during which the product can be used. The primary criterion for a given disinfection period (corresponding to a minimum potential recommended disinfection period) is that the number of bacteria recovered by me must be reduced by an average value of not less than 3.0 logs within the given disinfection period . The number of molds and yeasts recovered by me should be reduced by an average value of not less than 1.0 log within the minimum recommended disinfection time without increasing to four times the minimum recommended disinfection time. The test procedures described above were followed to determine if the primary performance criteria would be passed at intervals of 5 minutes, 15 minutes, 30 minutes and 4 hours. The concentration of alexidine in this group of tests was formulated in amounts in the range of 0.0 to 4.0 ppm in combination with 0.0 or 0.8 ppm of PAPB, the latter being the amount of PAPB currently used in the multi-use commercial solutions for soft contact lenses. In the following Table 1 the results are shown.

TABLE 1 The results show that the addition of alexidine to polyhexamethylenebiguanide improved the antimicrobial efficacy, with this efficacy being more effective, commercially unacceptable, for practical reasons, at approximately 4.0 ppm, - so that any increase in antimicrobial efficacy would not be likely. if justified by the greater toxicity potential at higher concentrations of the antimicrobial agent. With respect to C. albicans, there seems to be a synergistic effect at periods of 15 minutes and 30 minutes, showing the combination of 2.6 ppm of alexidine and 0.8 ppm of PAPB greater efficacy than the sum of 2, 6 ppm of alexidine alone and 0.8 ppm of PAPB alone. EXAMPLE 6 This Example illustrates the microbicidal efficacy of solutions according to the present invention. The above test procedures were used to evaluate the antimicrobial efficacy against C. albicans of disinfecting solutions such as those prepared in Example 4, but containing bis (biguanide) alexidine at various concentrations, ranging from 1 ppm to 4 ppm, and the biguanide polymer at various concentrations, ranging from 0.3 to 1.5 ppm. Table 2 shows the results after a 5 minute soak, in Table 3 after a 15 minute soak, in Table 4 after a 30 minute soak and in Table 5 after a soak of 45 minutes. minutes Tables 6 to 9, corresponding, respectively, to Tables 2 to 5, compare the theoretical death, based on the sum of the individual disinfecting agents, against actual death using the combination of disinfecting agents. For this calculation, the following equation was used: log 10 (explO (PHMB) + explO (alexidine)). In other words, to calculate the theoretical log death, the log reduction death values for each disinfecting agent were converted separately into the numbers of dead organisms and these values were then summed and a new log value was derived for the sum. TABLE 2 (5 minutes) TABLE 3 (15 minutes) TABLE 4 (30 minutes) TABLE 5 (45 minutes) TABLE 6 (5 minutes) ppm Alex / 0.8 ppm PHMB 1.1 1.6 ppm Alex / 0.8 ppm PHMB 1.2 2.8 ppm Alex / 1.5 ppm PHMB 1.1 1.1 ppm Alex / 1.5 ppm PHMB 1.2 1.5 ppm Alex / 1.5 ppm PHMB 1.2 2, 6 ppm Alex / 1.5 ppm PHMB 1.4 3.4 TABLE 7 (15 minutes) TABLE 8 (30 minutes) TABLE 9 (45 minutes) The above results show synergistic microbicidal effects against C. albi cans, where the death log of the combination of alexidine and PHMB, in a good proportion of the cases, is higher than the sum of those of the individual disinfectants, whose effects Synergies are evident, starting with the results after 15 minutes. At 45 minutes, these synergistic effects may be less evident, when a greater proportion of the microorganisms have already been killed. Based on the above data, Figure 1 shows the biocidal efficacy against C. albi cans of the test solutions containing the combination of alexidine and PHMB, after 15 minutes, in comparison with the theoretical efficacy, based on to the sum of individual solutions containing, respectively, alexidine alone and PHMB alone. Figure 2 shows the biocidal efficacy against C. albicans of the test solutions after a period of 30 minutes compared to the theoretical efficacy. Having described the invention together with specific examples thereof, this is only illustrative. Accordingly, many alternatives, modifications and variations will be apparent to those skilled in the art in light of the foregoing description and are therefore intended to encompass all such alternatives, modifications and variations insofar as they are within the spirit and scope of the appended claims.

Claims (15)

Claims

1. An ophthalmically safe disinfecting solution for contact lenses consisting of an aqueous solution consisting of the following components: (a) an i-crobicidal effective amount of a bis (biguanide) in an amount of about 0.10 to about 4.0 ppm, in the form of a water-soluble salt or as a free base, whose bis (bi-guanide) has the following general formula: R1-HC-NH-C-NH- (CH2) n-NH-C-NH-C -NH-R2 (I) II II II II NH NH NH NH where R1 and R2 are independently selected from the group consisting of alkyl of 4-12 branched or unbranched carbon atoms, an alkoxyalkyl ether or alkylsulfide radical of 4-12 carbon atoms or a cycloalkyl or cycloalkylalkyl radical of 5 -12 carbon atoms and n is 4 to 16; (b) a polymeric biguanide, in a total amount of about 0.10 to about 3.0 ppm, having the formula: X1- [-Z-NH-C-NH-C-NH-] nZ-X2 II II NH NH where Z is an organic divalent bridging group that can be the same or different along the polymer, n is on average at least 3 and X1 and X2 are independently selected from the groups -NH2 and -NH-C-NH-CN; II NH (c) an effective amount of a buffering agent; and (d) water in an amount of at least about 80% by weight.

2. The ophthalmically safe disinfectant solution of claim 1, wherein R1 and R2 are independently selected from the group consisting of a branched or unbranched alkyl radical, alkoxyalkyl ether or alkylsulfide thioether of 6 to 10 carbon atoms and n is 4 to 10.

3. The ophthalmically safe disinfectant solution of claim 1, which contains a polymeric biguanide which is a mixture of molecules with the general formula: X1- (CH2) 3- [- (CH2) 3-NH-C-NH-C-NH- (CH2) 3-] n "(CH2) 3 ~ X2 II II NH NH where X1 and X2 are as defined above and n is, on average, 5 to 20.

4. The ophthalmically safe disinfectant solution of claim 1, further including a surfactant in an amount of 0.01 to 5.0 percent.

5. The ophthalmically safe disinfectant solution of claim 4, wherein the surfactant is a neutral or non-ionic surfactant having a plurality of poly (oxyalkylene) chains, each of which poly (oxyalkylenes) contains repeating units (-OR), wherein R is independently an alkylene having from 2 to 6 carbon atoms.

6. The ophthalmically safe disinfectant solution of claim 4, wherein the surfactant is a neutral or non-ionic surfactant consisting of a block copolymer of poly (ethylene oxide) and poly (propylene oxide) segments.

7. The ophthalmically safe disinfectant solution of claim 1, wherein the amount of bis (biguanide) is 1.0 to 3.0 ppm.

8. The ophthalmically safe disinfectant solution of claim 1, wherein the amount of polymeric biguanide is 0.1 to 2.0 ppm.

9. A method of disinfecting, or cleaning and disinfecting, a soft contact lens with a multipurpose solution or an effective multipurpose solution, whose method consists of: (a) soaking the lens in a solution, so that disinfection is obtained acceptable of the contact lens with the solution, whose solution consists, in terms of formulation, in the following components: (i) a microbicidal effective amount of a bis (biguanide) in an amount of about 0.1 at about 4.0 ppm, in the form of a water-soluble salt or as a free base, whose bis (bigua-nide) has the following general formula: R ^ NH-C-NH-C-NH-ICHain-NH-C-NH- C-NH-R2 (I) II II II II NH NH NH NH where R1 and R2 are independently selected from the group consisting of alkyl of 4-12 carbon atoms branched or unbranched, an alkoxyalkyl ether or alkylsulfide radical of 4-12 carbon atoms or a cycloalkyl or cycloalkylalkyl radical of 5-12 carbon atoms and n is 4 to 16; (ii) a polymeric biguanide in an amount of about 0.10 to about 3.0 ppm, which polymeric biguanide has the following general formula: X1- [-Z-NH-C-NH-C-NH-] nZ -X2 NH NH where Z is an organic divalent bridge group that can be the same or different along the polymer, n is at least 3 average and X1 and X2 are independently selected from the groups -NH2 and -NH-C -NH-CN, and II NH (iii) an effective amount of an agent also; and (b) directly placing the treated lens in the user's eye, where (i) it is not necessary to rinse with a different solution before repositioning in the eye and (ii) no other solution is required for the daily treatment of the eye. the lens.

10. The method of claim 9, wherein the method does not include rubbing the lens with the solution, as it is not required by the instructions for use of the product.

11. The method of claim 9 or 10, wherein R1 and R2 are independently selected from the group consisting of a branched or unbranched alkyl radical, alkoxyalkyl ether and alkylsulfide thioether and n is 4 to 10.

12. The method of claim 11, wherein the polymeric biguanide is a mixture of polymeric biguanides having the following formula: X1- (CH2) 3- [- (CH2) 3-NH-C-NH-C-NH- (CH2) 3-] n- (CH2) 3-X2 NH NH where X1 and X2 are as defined above and n is, on average, 5 to 20.

13. The method of claim 9 or 10, wherein the solution is used to clean a lens that is made or planned for replacement after no more than about 30 days of use.

14. The method of claim 13, wherein the lens is planned or made for replacement after no more than about 14 days of use.

15. The method of claim 9 or 10, wherein the solution is used to clean a lens that is made with a polymer consisting of about 0.0 to 5 mole percent of repeating units derived from methacrylic acid (AMA), a to 99 mole percent of repeating units derived from hydroxyethyl methacrylate and about 0.5 to 5 mole percent of crosslinking repeating units.