JP5613779B2 - Contact lens solution - Google Patents

Description

  TECHNICAL FIELD The present invention relates to a contact lens solution, and more particularly to a contact lens solution that is suitably used as a contact lens disinfecting composition and that is easy to manufacture and excellent in stability.

  Conventionally, liquid preparations containing antibacterial agents used for disinfection of contact lenses are generally manufactured as sterile preparations. The sterilization process is sterilization by filtration. Usually, sterilization by an autoclave or a combination thereof is performed.

  However, among them, autoclave sterilization employs a process of cooling after heating to 121 ° C or higher, so in the case of a liquid preparation containing a component having low thermal stability, In addition, since a heat-resistant / pressure-resistant production line and cooling equipment are required, the manufacturing time is also increased due to heating and cooling.

  On the other hand, aseptic processing by filtration sterilization makes it possible to produce a liquid at room temperature. If the liquid does not have any problem in filterability or influence on the filter, the liquid is more effective than autoclave sterilization. In production, there are many advantages, and in the unlikely event that foreign materials mixed in from the raw material or the production line can be removed with a filter, it is usual to adopt a sterilization process by filtration sterilization. Will be considered as the first option. In addition, in such a sterilization process by filtration sterilization, if some raw materials to which the liquid agent is given have problems with filterability, only the poorly filterable components are autoclaved and used. Therefore, a system for aseptically mixing other components that have been separately sterilized by filtration, or a production system for mixing all the components and sterilizing by autoclave must be employed.

  On the other hand, liquids for contact lenses are used in various types to increase slipperiness when scrubbing the lens, cushioning effect when worn on the eye, and imparting a moistening effect due to components adhering to the lens surface. Attempts have been made to mix a thickener, but such a thickener is a raw material (component) that has a large effect on filterability and stability. Depending on the type, the filterability may deteriorate. It is known that problems such as lowering long-term stability are caused. For this reason, when selecting a thickener, not only the touch and moisturizing effects, but also the influence on the stability of the liquid agent and the determination from the viewpoint of production cost become important factors.

  By the way, in the solution for disinfecting contact lenses, as a thickener, cellulose-based, guar gum-based, PVA-based, PVP-based and the like are mainly used. The present condition is that it is limited to PVA type | system | group and some cellulose type | system | group thickeners (model number: HPMC2910) as a thickener which can be sterilized by filtration in the state which provided the thickening effect. Among them, the PVA thickener is very excellent in filterability, but when the liquid agent containing the PVA thickener is stored for a long time, the unsaponified acetate is hydrolyzed. However, there is a problem that the pH of the liquid agent gradually decreases. Therefore, in a multi-purpose solution that directly touches the eyes, such a pH decrease inherently causes eye irritation. . And from such a situation, when manufacturing the liquid agent which considered adoption of the filtration sterilization process process, as a thickener, a cellulose thickener (HPMC2910) is considered to be the 1st option.

  In addition, as a solution for disinfecting contact lenses, a one-component type multi-purpose that is formulated by mixing a low concentration of a cationic disinfectant that does not require neutralization from a hydrogen peroxide-based disinfectant that requires neutralization. Solutions are becoming mainstream. The cationic disinfectant used in this multipurpose solution is mainly PHMB (polyhexamethylene biguanide), which is a disinfectant for biguanide polymers, and Polyquad, which is a disinfectant for quaternary ammonium salt polymers. Types are targeted. Among them, polyquads have been reported to have a low disinfection effect against fungi and amoeba. Therefore, it is considered that a low molecular disinfectant having a high disinfection effect against fungi and amoeba may be used in combination with such polyquads. However, the low molecular weight disinfectant has a problem of high toxicity, and there is a concern about a problem due to accumulation in the lens. On the other hand, PHMB has a high disinfection effect against not only bacteria but also fungi and amoeba, and is a well-balanced disinfectant, and thus has been used in many multipurpose solutions.

  Therefore, it is considered that a liquid composition capable of being sterilized by filtration can be realized by using PHMB as the disinfectant and using a cellulose-based thickener having high filterability as the thickener. Unfortunately, when such a PHMB disinfectant and a cellulosic thickener (model number: HPMC2910) are combined, some reaction is induced between them and the disinfecting action by PHMB. There is a problem in that the stability of the sterilization is reduced, and the disinfection effect decreases with time.

  Incidentally, JP-A-8-504346 (Patent Document 1) discloses a liquid agent for contact lenses containing a polypeptide such as protamine, polyarginine, polylysine or the like for preventing protein adhesion. In this case, HPMC (hydroxypropylmethylcellulose) is exemplified as one of the barrier component coatings constituting the tablet, but there is no clarification regarding the type of such HPMC. No problem has been clarified with respect to the problem in the liquid for contact lenses containing HPMC.

  Patent No. 3813133 (Patent Document 2), Japanese Patent No. 3693656 (Patent Document 3), Japanese Patent No. 3693657 (Patent Document 4), etc., as a disinfectant in a solution for disinfecting and storing contact lenses. In addition to using polylysine, in order to improve its antibacterial activity, it has been clarified that POE lauryl ether type surfactant, betaine type surfactant, sucrose laurate, etc. are used in combination, and as a thickener Although the use of HPMC is also disclosed, the type of HPMC that can be used therein is not disclosed. Similarly, in Japanese Patent No. 4255393 (Patent Document 5), as a further additive in a contact lens solution containing polylysine as a disinfectant, cellulose and its derivatives represented by HPMC, Although it is exemplified that a thickener such as PVA, PVP, etc. can be blended, there is no clarification as to the type of HPMC that can be used.

JP-T 8-504346 Japanese Patent No. 3813133 Japanese Patent No. 3693656 Japanese Patent No. 3693657 Japanese Patent No. 4255539

  Here, the present invention has been made in the background of such circumstances, and the problem to be solved is a contact lens with excellent stability that can advantageously employ a manufacturing process by filtration sterilization. It is another object of the present invention to provide a method for producing an antiseptic solution for contact lenses having such excellent characteristics in an industrially advantageous manner.

  And as a result of intensive studies to solve such problems, the present inventors have used a cationic polypeptide as an antibacterial agent in the production of a contact lens disinfectant solution, while being used as a thickener. Among various types of known hydroxypropylmethylcellulose (HPMC), by using a specific substitution type of hypromellose 2910, a high disinfection effect against fungi, acanthamoeba, etc. can be maintained for a long time. The present inventors have found that it is possible to industrially produce a solution by filtration sterilization, and that the problems inherent in the conventionally known solution for disinfecting contact lenses can be solved.

Accordingly, the present invention has been completed based on such findings, and the gist thereof includes a cationic polypeptide antibacterial agent and hypromellose 2910 as a thickener, and 25 The liquid for contact lenses is characterized in that the kinematic viscosity at 0 ° C. is adjusted to 0.8 to 15 mm ² / s and does not contain a biguanide polymer .

  According to one of the preferred embodiments of the contact lens solution according to the present invention, the above-mentioned cationic polypeptide antibacterial agent includes polylysine, protamine, cationized collagen, cationized keratin, cationized soy protein, and cationization. It will be selected from the group consisting of silk.

  In the present invention, the cationic polypeptide antibacterial agent is preferably contained in a proportion of 0.1 to 10,000 ppm.

  Furthermore, the liquid agent for contact lenses according to the present invention includes at least one of an isotonic agent, a chelating agent, a buffering agent and a surfactant in addition to the above-mentioned cationic polypeptide antibacterial agent and hypromellose 2910. , And can be included as necessary.

  In addition, in the contact lens solution according to the present invention, the pH is preferably adjusted within the range of 6-8.

In the present invention, in order to produce such a contact lens solution, (a) at least a cationic polypeptide antibacterial agent and hypromellose 2910 are added and dissolved in an aqueous medium, A step of preparing a solution having a kinematic viscosity at 25 ° C. of 0.8 to 15 mm ² / s, and (b) a step of sterilizing the obtained solution using a membrane filter. The gist of the present invention is to employ a method for producing a liquid preparation for contact lenses characterized in that it is included.

  Thus, in the contact lens solution according to the present invention, the cationic polypeptide antibacterial agent is combined with hypromellose 2910, which is of a specific substitution degree type of HPMC, as a thickener, and has a predetermined behavior. By preparing the liquid so as to have a viscosity, it is possible to maintain a high disinfecting effect against fungi, Acanthamoeba, etc. over a long period of time, and stably maintain the liquid pH over a long period of time. In addition, the cationic polypeptide antibacterial agent and hypromellose 2910 can be dissolved and contained, and the solution adjusted to a predetermined kinematic viscosity can be easily sterilized by filtration. Because of this, the target contact lens solution can be processed in large quantities, and filtration sterilization can be performed at an advantageous cost. It's has become possible.

  In addition, according to the method for producing a contact lens solution according to the present invention, a filtration sterilization step can be adopted, so that a large amount of treatment is possible. Therefore, filtration costs for removing foreign substances, fungi and acanthamoeba Thus, the sterilization cost can be advantageously reduced, which can greatly contribute to the reduction of the product cost, and an industrially advantageous production method can be established.

  By the way, the liquid preparation for contact lenses according to the present invention is mainly composed of an aqueous medium, in which a cationic polypeptide antibacterial agent and hypromellose 2910 as a thickener are contained as essential components. It is adjusted to kinematic viscosity and has great characteristics.

  Specifically, the cationic polypeptide antibacterial agent used as an essential component in the present invention is known as a relatively high molecular weight disinfectant in a contact lens disinfectant solution, for example, polylysine, protamine, Components such as cationized collagen, cationized keratin, cationized soy protein, and cationized silk are appropriately selected and used.

  Such a cationic polypeptide antibacterial agent is generally contained at a ratio of 0.1 ppm or more and 10,000 ppm or less in the liquid for contact lenses in order to effectively exert antibacterial action thereby on the contact lens. In particular, it is preferably contained in a proportion of 1 to 1000 ppm. Here, since excessive inclusion of such an antibacterial agent may cause harmful effects on the eye, it is desirable to avoid excessive inclusion.

Further, it hypromellose 2910, which is another essential component in the contact lens liquid agent according to the present invention is intended to be used as a thickener, a part of the hydrogen of the hydroxyl groups of cellulose are, or a methyl group (-CH _3), This is one type of substitution of a cellulose compound (hydroxypropylmethylcellulose: HPMC) having a structure substituted with a hydroxypropyl group (—CH ₂ CHOHCH ₃ ). That is, such hypromellose 2910 used in the present invention contains 28.0 to 30.0% methoxy group and 7.0 to 12.0% hydroxypropoxy group on a weight basis, It is highly safe to the living body, is sufficiently ophthalmically acceptable, and does not affect the shape or physical properties of the contact lens.

In the contact lens solution containing such hypromellose 2910 together with the cationic polypeptide antibacterial agent, the kinematic viscosity is 0.8 to 15 mm ² / s at 25 ° C. Will be adjusted. If this kinematic viscosity is too low, the thickening effect will not be sufficient, which will cause inconvenience in use as a liquid for contact lenses. On the other hand, if the kinematic viscosity becomes too high, the solution will be sterilized by filtration. It is difficult to do. A preferred range for such kinematic viscosity is in the range of 1 to 10 mm ² / s.

  In order to give such kinematic viscosity, the content of hypromellose 2910 will be appropriately adjusted according to the viscosity grade used, but is generally about 0.01 to 10% on a weight basis, preferably It is added and contained within the range of about 0.1 to 5%.

  Thus, the contact lens solution according to the present invention uses a cationic polypeptide antibacterial agent, and uses a specific cellulosic compound hypromellose 2910 as a thickener to be combined therewith. As in the prior art, the cationic polypeptide antibacterial agent and hypromellose can be obtained by adding and dissolving in a suitable aqueous medium and adjusting to a specific kinematic viscosity. In addition to the two inclusion components of 2910, if necessary, additional components such as isotonic agents, chelating agents, buffering agents, surfactants and the like used in general liquids for contact lenses are described below. 1 type or 2 types or more may be appropriately selected and added at a normal addition ratio. It is. In addition, it is preferable that such an additive component has high safety to the living body, is sufficiently ophthalmically acceptable, and has no influence on the shape or physical properties of the contact lens. It is desirable to be used within the quantitative range to be satisfied, and thereby, various functions according to the added components are advantageously imparted to the contact lens liquid without obstructing the effects of the present invention. It becomes possible.

  For example, the isotonic agent contained in the contact lens solution according to the present invention and used to adjust its osmotic pressure includes sodium chloride, potassium chloride, saccharides, sugar alcohols and polyhydric alcohols or ethers thereof or the like. Generally, at least one compound selected from the group consisting of esters will be used. Specific examples of the compound include glycerin, propylene glycol, polyethylene glycol, mannitol, sorbitol, dextrin, dextran and the like in addition to the alkali metal chloride described above. And it is preferable that the osmotic pressure of the contact lens solution is generally adjusted to about 200 to 400 mOsm / kg using such an isotonic agent.

  In addition, the chelating agent has the purpose of suppressing the deposition or adsorption of polyvalent metal ions such as calcium on the contact lens, and improving the stability of the liquid agent, thereby favoring its long-term storage. Various known ones are appropriately selected and used. Specifically, ethylenediaminetetraacetic acid (EDTA) and a salt thereof, for example, ethylenediaminetetraacetic acid.2 sodium (EDTA.2Na), ethylenediaminetetraacetic acid.3 sodium (EDTA.3Na), and the like can be used.

  Furthermore, in the contact lens solution according to the present invention, when the cleaning property of the contact lens is increased or the liquid component contained therein is water-insoluble, it is stably dissolved (solubilized) in an aqueous medium. Various known surfactants can be added and contained for the purpose of making them. In addition, as such a surfactant, a conventionally known anionic surfactant, nonionic surfactant, amphoteric interface may be used as long as it is highly safe to living bodies and does not affect the contact lens. Any of an activator and a cationic surfactant can be employed, and can be advantageously added and contained at a concentration that does not impair the function and effect of the present invention.

  Specific examples of such surfactants include, for example, polyoxyethylene-polyoxypropylene block copolymers and derivatives thereof, polyethylene glycol derivatives such as polyoxyethylene alkylphenyl ether formaldehyde condensates such as tyloxapol, and sesquiolein. Sorbitan fatty acid esters such as acid sorbitan, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monooleate (for example, polysorbate 80), glycerin fatty acid esters such as glyceryl monostearate, polyethylene glycol fatty acids such as polyethylene glycol monostearate Esters, polyoxyethylene alkyl ethers such as polyoxyethylene lauryl ether, polyoxyethylene castor oil, poly Kishiechiren hardened castor oil, polyoxyethylene alkyl ether carboxylic acids and salts thereof, sucrose fatty acid esters and the like, and be used to advantage. Among them, in particular, Pluronic, Pluronic R, Tetronic, Tetronic R, which are polyoxyethylene-polyoxypropylene block copolymers commercially available as nonionic surfactants (above, Germany: manufactured by BASF) ), Specifically, poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, tetronic 904, tetronic 908, tetronic 1304, tetronic 1107, polyoxyethylene sorbitan monooleate polysorbate 80, It is desirable to use polyoxyethylene hydrogenated castor oil.

  In addition, the contact lens solution according to the present invention may irritate the eye or cause eye damage if its pH value or osmotic pressure becomes too high or too low. In general, the pH value of such a contact lens solution is adjusted to about 6 to 8 by adding an appropriate pH adjusting agent, buffering agent, etc., and particularly around pH = 7.0. It is desirable.

  As the pH adjuster used for such pH adjustment, sodium hydroxide, hydrochloric acid or the like is used, while the pH of the solution is effective in the above-described range and is safe for the eyes. As the buffering agent for maintaining the temperature, it is appropriately selected from conventionally known various agents and used. Specifically, for example, acids such as phosphoric acid, boric acid, carboxylic acid, oxycarboxylic acid, and salts thereof (for example, sodium salt), Good-Buffer and tris (hydroxymethyl) aminomethane (TRIS) Bis (2-hydroxyethyl) iminotris (hydroxymethyl) methane (Bis-Tris), sodium hydrogen carbonate, etc. are mentioned because they are safe for the eyes and can reduce the influence on the contact lens. I can do it.

  By the way, the contact lens solution according to the present invention is prepared using a specific combination of a cationic polypeptide antibacterial agent and hypromellose 2910 as a thickener, as described above. As a liquid disinfectant for lenses, it can exhibit excellent characteristics. However, in a quantitative range that does not inhibit the effect of the use of such a specific thickener, other viscosities other than hypromellose 2910 are used. It is also possible to add a thickener or thickener. Examples of such thickeners include various gums such as polysaccharides such as chondroitin sulfate, hyaluronic acid, gluconic acid, and salts thereof, mucopolysaccharide, and heteropolysaccharide; polyvinyl alcohol, poly- Examples thereof include synthetic organic polymer compounds such as N-vinylpyrrolidone, polyethylene glycol, polypropylene glycol, and polyacrylamide; cellulose derivatives such as hydroxyethyl cellulose, carboxymethyl cellulose, and methyl cellulose; starch derivatives.

  In addition to the above, the liquid agent for contact lenses according to the present invention is added with the same drug component as that of the prior art, for example, an anti-inflammatory agent for suppressing intraocular inflammation caused by stress or wearing of contact lenses. In addition, for the purpose of eliminating the feeling of foreign objects and itching when wearing contact lenses, a refreshing agent is added, and various vitamins and amino acids are used for the intended contact lens solution. Depending on the case, it can be added appropriately.

  Such a contact lens solution according to the present invention is prepared by adding and incorporating the above-described components in an appropriate amount in an appropriate aqueous medium, as in the prior art. However, as an aqueous medium used at that time, in addition to water itself such as tap water, purified water, and distilled water, as long as it is a solution mainly composed of water, physiological saline or an aqueous solution containing sodium chloride, Needless to say, it is also possible to use a contact lens solution or the like.

  In addition to the essential components of the cationic polypeptide antibacterial agent and hypromellose 2910 used in accordance with the present invention, it is necessary to adopt any special technique when adding and dissolving other additive components in a predetermined aqueous medium. However, it can be easily carried out by dissolving each component in an aqueous medium, as in the case of preparing an ordinary aqueous solution. In particular, in the present invention, it is easy to perform filtration sterilization treatment on the aqueous solution obtained by dissolving these components, thereby enabling mass treatment, and the contact according to the present invention. The lens solution can be advantageously obtained industrially at a high productivity and therefore at a low production cost. In addition, it is generally recommended to carry out such filtration sterilization treatment of an aqueous solution by filtering using a membrane filter having a pore diameter of about 0.1 to 10 μm. Moreover, this filtration sterilization process effectively achieves a sterilization process as well as removal of foreign substances from the solution, and the desired sterile contact lens solution can be advantageously obtained.

  The contact lens solution obtained according to the present invention obtained as described above has sufficiently secured safety for the eye, is easy to manufacture, and has improved productivity. Therefore, it is advantageously used as a liquid for disinfecting contact lenses. Such a contact lens solution may be used as, for example, a contact lens sterilizing solution or disinfectant, a contact lens cleaning solution, a contact lens preserving solution, a contact lens rinsing solution, and the like. It can be advantageously used as a multipurpose solution (multipurpose solution: MPS) such as a cleaning / preserving solution, a cleaning / preserving / rinsing solution, and a sterilizing / cleaning solution.

  In addition, as a contact lens which is the target of the liquid agent for contact lens according to the present invention, the kind thereof is not limited at all, and for example, soft contact classified into all of non-water content, low water content, high water content, etc. The lens and the hard contact lens can be the object, and the material of the contact lens is not limited at all in applying the present invention.

  Hereinafter, some examples of the present invention will be shown and the present invention will be more specifically clarified, but the present invention is not limited by the description of such examples. It goes without saying. In addition to the following examples, the present invention includes various changes and modifications based on the knowledge of those skilled in the art without departing from the spirit of the present invention, in addition to the above specific description. It should be understood that improvements can be made.

  First, in order to prepare a large number of test solutions to be contact lens solutions according to the present invention and contact lens solutions according to comparative examples, various disinfectants (polypeptides) shown in Table 1 below, various comparative disinfectants, Various thickeners, chelating agents, surfactants, buffer materials, and isotonic agents were obtained from the companies shown in Table 1 and prepared.

-Preparation of contact lens solution (test solution)-
Various test solutions (No. 1) whose initial pH was adjusted to 7.4 by adding predetermined blending components to sterilized purified water at various ratios shown in Tables 2 to 5 below. To No. 24) were prepared.

  And about the obtained various test solutions (No.1-No.24), the following bacteria (Pseudomonas aeruginosa) and fungi (Candida) disinfection test methods, amoeba disinfection test methods, kinematic viscosity The disinfection effect (4 hours), filterability, and kinematic viscosity (25 ° C.) were examined according to the measurement method and the filterability evaluation method, and the results are also shown in Tables 2 to 5 below.

-Disinfection test method for bacteria (Pseudomonas aeruginosa) and fungi (Candida)-
The following tests were carried out in accordance with ISO 14729 guidelines that stipulate test methods for disinfection effects on contact lenses and care products.

First, 9.9 mL of each test solution prepared above was put in a test tube, and 10 mL of Pseudomonas aeruginosa NBRC 13275 or Candida albicans IFO 1594 was added thereto. Bacteria corresponding to each test solution containing 0.1 mL of the bacterial solution containing ⁸ to 10 ⁹ cfu / mL and then stirred, and finally containing the number of bacteria of 10 ⁶ to 10 ⁷ cfu / mL Each suspension was prepared. Then, after leaving them to stand at 23 ° C. for 4 hours, 1 mL of each of these bacterial suspensions was taken out, and the viable cell count of 1 mL of the sample was measured by a plate dilution method using 20 mL of glucose peptone agar medium. And after calculating the viable cell count in 1 mL of each cell suspension from this viable cell count, the log reduction number converted to logarithm was determined according to the following formula.
Number of bacteria decreased = log (number of viable bacteria in 1 mL of bacterial suspension immediately after preparation)
-Log (number of viable bacteria in 1 mL of bacterial suspension after standing treatment)
The bactericidal efficacy of each test solution was evaluated from the above-mentioned log reduction value. In addition, the evaluation standard was set to (circle) when satisfy | filling First Criteria (related to sterilization) in ISO14729, and set to x when not satisfy | filling.

-Test method of amoeba-
Nutrients of pre-cultured Acanthamoeba castellanii ATCC 50370 were recovered from the flask, and a suspension of 5 × 10 ⁵ cells / mL was prepared using 1/4 Ringer's solution. On the other hand, 5 mL of each test solution is put into a test tube, 50 μL of the above-mentioned Acantham amoeba suspension is added and stirred, and finally a suspension containing 5 × 10 ³ cells / mL amoeba is obtained. , Respectively. Then, after leaving them at a temperature of 22 ° C. for 4 hours, 20 μL of the suspension of such amoeba is collected and mixed with 180 μL of 1/4 Ringer solution added with lecithin polysorbate (LP) as a neutralizing solution. Thus, 10-fold serial dilution was appropriately performed. Then, 50 μL of Eschelichia coli suspension prepared to 1 × 10 ⁸ cfu was added to each test solution serially diluted 10 times, and cultured for 14 days. Then, the number of viable amoeba was measured from the number of wells in which the growth of amoeba was observed, and the log reduction value was calculated based on the following formula.
Log reduction = log (number of surviving amoeba in 1 mL immediately after adjustment)
-Log (number of surviving amoeba in 1 mL of sample after treatment)

-Kinematic viscosity measurement method-
The kinematic viscosity for each test solution was measured using an Ubbelohde viscometer (manufactured by Shibata Scientific Instruments Co., Ltd.). At that time, an Ubbelohde viscometer having a coefficient such that the number of seconds flowing down is 200 to 1000 seconds is selected. The measurement is performed in a constant temperature water bath at 25 ° C. so that there is no temperature change. And kinematic viscosity (unit: mm < ² > / s) can be calculated | required by the product of the flow-down seconds of each test liquid measured with this Ubbelohde viscometer and the coefficient of the Ubbelohde viscometer.

-Evaluation method of filterability-
Use a membrane filter with a diameter of 47 mm (Nihon Pole, Super EKV, pore size: 0.2 μm) and set it in an in-line stainless steel filter holder for 47 mm disks (Nihon Millipore, effective area 13.8 cm ² ). Then, each test solution was filtered at a pressure of 1 kgf / cm ² , and the filtration amount after 3 hours was compared. And when the amount of filtration after 3 hours was 2L or more, it evaluated as (double-circle), when it was 1L or more, (triangle | delta) between 500 mL-1L, and evaluated as x in less than 500 mL.

As is apparent from the results in Tables 2 to 5, the polypeptide disinfectant and hypromellose 2910 were combined according to the present invention, and the kinematic viscosity (25 ° C.) was adjusted to 0.8 to 15 mm ² / s. Test solution No. In 1-4, 6, 7, 14-18, it was recognized that it shows the outstanding disinfection effect and filterability. On the other hand, test liquid No. whose kinematic viscosity (25 degreeC) became larger than 15 mm < ² > / s. 5, the filterability is poor and the filtration sterilization operation cannot be advantageously performed, and even if a polypeptide disinfectant is used, as a thickener, hypromellose 2906, which is a different type from hypromellose 2910, is used. No. 2208, or test solution No. using methylcellulose, hydroxyethylcellulose, or PVP. In 8-12, even if kinematic viscosity (25 degreeC) was lower than 15 mm < ² > / s, it was recognized that filterability is bad. Furthermore, test solution No. using other disinfectant (comparative disinfectant) other than polypeptide disinfectant. In 20-24, either disinfection effect or filterability was not enough, and it was recognized that it lacked practicality.

-Evaluation of long-term stability-
The long-term stability of each test solution was examined using the test solutions 3, 6, 13 to 15, and 19 prepared in Tables 2 to 4 above.

  Specifically, after each test solution was stored at 45 ° C. for 6 months, the disinfection effect was examined in the same manner as described above, and the pH of the test solution was measured and shown in Tables 2 to 4 above. The disinfection effect and the pH value immediately after preparation of the test solution are shown in Table 6 below.

As is apparent from the results in Table 6, the pH of the test solutions 3, 6, 14, and 15 according to the present invention hardly changes even after storage at 45 ° C. for 6 months, and the disinfecting effect. It was recognized that the sterilization effect was excellent with almost no change. On the other hand, in the test solution 13 using PVA as a thickener, although the disinfecting effect is excellent, the pH of the solution is remarkably lowered by long-term storage, which may cause a problem in long-term storage stability. It became clear. In addition, in the case of the test liquid 19 using polybiguanide (PHMB) as a disinfectant, it was revealed that the disinfection effect is remarkably lowered by long-term storage.

Claims (6)

Contains a cationic polypeptide antibacterial agent and hypromellose 2910 as a thickener, and is adjusted to have a kinematic viscosity at 25 ° C. of 0.8 to 15 mm ² / s , including a biguanide polymer A liquid for contact lenses, characterized in that it does not .
  The contact lens solution according to claim 1, wherein the cationic polypeptide antibacterial agent is selected from the group consisting of polylysine, protamine, cationized collagen, cationized keratin, cationized soybean protein, and cationized silk.   The liquid agent for contact lenses according to claim 1 or 2, wherein the cationic polypeptide antibacterial agent is contained in a proportion of 0.1 to 10,000 ppm.   The contact according to any one of claims 1 to 3, further comprising at least one of an isotonic agent, a chelating agent, a buffer material, a pH adjusting agent, and a surfactant. Lens solution.   The contact lens solution according to any one of claims 1 to 4, wherein the pH is 6 to 8. A method for producing a contact lens solution according to any one of claims 1 to 5,
Adding at least a cationic polypeptide antibacterial agent and hypromellose 2910 in an aqueous medium and dissolving them, and preparing a solution having a kinematic viscosity at 25 ° C. of 0.8 to 15 mm ² / s;
The step of sterilizing the obtained solution by filtration using a membrane filter;
The manufacturing method of the liquid agent for contact lenses characterized by including.