WO2004011993A1

WO2004011993A1 - Liquid enzyme preparation for contact lenses

Info

Publication number: WO2004011993A1
Application number: PCT/JP2003/009426
Authority: WO
Inventors: Kazuaki Yamamoto; Yusuke Nagai; Masaki Imayasu
Original assignee: Menicon Co., Ltd.
Priority date: 2002-07-29
Filing date: 2003-07-25
Publication date: 2004-02-05
Also published as: AU2003255159A1; JPWO2004011993A1; JP4402593B2

Abstract

A liquid enzyme preparation for contact lenses which contains a water-soluble high-molecular weight organic solid having an average molecular weight of 800 to 100000, a viscosity controlling gent and an enzyme. Using this liquid enzyme preparation, it is possible to lessen the swelling or deformation of soft contact lenses, which occur in the case of treating with an existing liquid enzyme preparation for contact lenses (comprising a water soluble low-molecular weight organic liquid and a protease) and irritation of eye tissues due to misuse of an enzyme preparation.

Description

Akira Itoda Liquid enzyme for contact lenses Technical field

The present invention relates to a liquid enzyme preparation for contact lenses. More specifically, the present invention relates to a liquid enzyme agent which is added to a treatment solution such as a cleaning preservative solution for contact lenses, a disinfectant and a cleaning preservative disinfectant and is brought into contact with the contact lens to remove stains on the contact lens. Background art

In order to remove protein stains attached to contact lenses, they are generally degraded and removed with proteolytic enzymes. To stabilize proteolytic enzymes, a method of forming an effective amount of the proteolytic enzyme in a solid form such as tablets, granules, and powders has been adopted.However, this method requires complicated labor during production and use. There was a problem that time was required. Liquid proteolytic enzymes have also been developed to solve these problems. For example, Japanese Patent Application Laid-Open No. Hei 11-18015 and Japanese Patent Application Laid-Open No. Hei 2-168224 disclose low molecular weight organic liquids such as glycerin, propylene glycol and polyethylene glycol, and proteolytic enzymes. Liquid enzyme preparations are described. In such prior art, a combination of a water-soluble low-molecular-weight organic liquid and a proteolytic enzyme was often seen, and a water-soluble low-molecular-weight organic liquid was clearly recognized as a main component for stabilizing the enzyme. However, when a water-containing soft contact lens is treated with an enzyme agent that stabilizes protein-degrading enzymes with a water-soluble low-molecular-weight organic liquid, the water-soluble low-molecular-weight organic liquid contained in the treatment liquid will To expand and deform the lens JP2003 / 009426

2 There is a problem that To avoid this problem, it is stated in the instruction manual that some of the commercially available protein-degrading enzyme preparations use one drop at a time. Is often done.

In addition, since the osmotic pressure of the treatment solution to which the proteinase-degrading enzyme containing water-soluble low-molecular-weight organic liquid as a main component is dropped is hypertonic, it may affect the lens and irritate the eye tissue when misused. There are also concerns. Disclosure of the invention

An object of the present invention is to provide a liquid enzyme agent for a contact lens that does not adversely affect a lens or eye tissue in view of the related art.

The present invention relates to a liquid enzyme preparation for contact lenses, comprising a water-soluble organic polymer solid having an average molecular weight of 800 to 1000, a viscosity modifier and an enzyme. In the liquid enzyme preparation for contact lenses, the water-soluble high molecular organic solid is preferably a polyalkylene glycol.

In the liquid enzyme preparation for contact lenses, the water-soluble high-molecular organic solid is preferably polyethylene glycol or polyethylene glycol monomethyl ether.

In the liquid enzyme agent for contact lenses, the viscosity modifier is preferably a water-soluble low molecular organic liquid.

The liquid enzyme agent for contact lenses preferably contains 5 to 45 wZw% of a water-soluble organic polymer solid.

The liquid enzyme preparation for a contact lens preferably contains 15 to 45 w / w% of a viscosity modifier. BEST MODE FOR CARRYING OUT THE INVENTION The liquid enzyme preparation for a contact lens of the present invention contains, as essential components, a water-soluble organic polymer solid having an average molecular weight of 800 to 100000, a viscosity modifier and an enzyme.

The enzymes contained in the liquid enzyme agent for contact lenses of the present invention include those that degrade proteins that are the main components of stains in contact lenses and those that degrade other stain components. Specific examples include, but are not limited to, proteolytic enzymes, lipolytic enzymes, and Z or glycolytic enzymes.

The water-soluble polymer organic solid used in the present invention means a fluid solid (for example, serine) or a solid, and a water-soluble synthetic polymer organic solid having no micelle-forming ability. Therefore, natural products such as proteins, cellulose, and polysaccharides are not included in the water-soluble high molecular weight organic solids herein.

The water-soluble organic polymer solid used in the present invention is not particularly limited as long as it has a mean molecular weight of 800 to 100,000, preferably 1,000 to 20,000. If the average molecular weight is less than 800, the characteristic water retention effect tends not to be exhibited, and if it exceeds 100000, the viscosity when the water-soluble high molecular weight organic solid is dissolved tends to be too high. It is thought that the water-soluble high molecular organic solid contributes to the stabilization of the enzyme by suppressing the hydrolysis reaction of the proteolytic enzyme due to the water retention effect of the polymer chain.

As the water-soluble high molecular weight organic solid in the liquid enzyme agent for contact lenses of the present invention, those having extremely high solubility in water (for example, those which dissolve in water at 20 ° C at least 15 w / w%) are preferable. And the viscosity of the solution is high (for example, 1 OPa · S) even when it is dissolved in multiple parts by weight. Are more preferred. Further, a water-soluble high molecular weight organic solid having a liquid pH in the neutral region after dissolution is also preferable.

In the liquid enzyme preparation for contact lenses of the present invention, the water-soluble high molecular organic solid includes, for example, a methyl group bonded to one of the terminal hydroxyl groups of polyethylene glycol, polypropylene glycol, and polyethylene dalicol. Polyalkylene glycols such as polyethylene glycol monomethyl ether, polyvinyl caprolactams such as polyvinylpyrrolidone and poly N-vinylcaprolactam, polyethers such as crown ether, polyacrylamide hydrochloride, polydimethylacrylamide and polyje Use of polyacrylamides such as tylacrylamide, hydroxyl-containing (meth) acrylates such as polyhydroxyethyl methacrylate, or polyols such as polyvinyl alcohol. Can Ru. Among water-soluble high molecular weight organic solids, polyalkylene glycols are preferred from the viewpoints of economy, solubility in water, viscosity of liquid enzyme, safety, and color, among which polyethylene glycol and polyethylene glycol monomethyl ether are preferred. Is more preferred. Among them, those having an average molecular weight of 1000 or more are most preferable.

The compounding amount of the water-soluble high molecular weight organic solid in the liquid enzyme preparation for a contact lens of the present invention is preferably 5 to 45 wZw%, more preferably 5 to 20 w / w%. If the amount of the water-soluble high-molecular organic solid is less than 5 wZw%, there is a tendency that the stability of the enzyme, the effect of reducing the osmotic pressure, and the effect of preventing the deformation of the lens are not sufficiently obtained. If it exceeds 45 wZw%, organic solids tend to precipitate when saturation solubility is reached due to temperature changes or the like, and viscosity tends to be too high.

The viscosity modifier used in the present invention, when used in combination with a water-soluble organic polymer solid, is a more enzymatic agent than when the stability of the enzyme is achieved using only the water-soluble organic polymer solid Can reduce the viscosity. In other words, by adding the viscosity modifier to the liquid enzyme agent for contact lenses, it has a function of facilitating dripping of the liquid enzyme agent and facilitating mixing of the liquid enzyme agent after dropping with the washing preservation solution. However, when the enzyme is stabilized only with a viscosity modifier, the viscosity of the enzyme agent can be kept low, but the osmotic pressure of the processing solution mixed with the washing preservation solution becomes hypertonic, which may affect the lens or cause misuse. There are also concerns about irritation of the eye tissue at the time. Therefore, in the liquid enzyme preparation of the present invention, it is important to use a water-soluble organic polymer solid and a viscosity modifier together. Specific examples of such a viscosity modifier include, for example, a water-soluble low-molecular-weight organic liquid.

The low-molecular organic liquid means an organic liquid that is fluid at normal temperature and normal pressure. In the liquid enzyme preparation for contact lenses of the present invention, for example, glycerin, propylene glycol, low-molecular polypropylene glycol, ethylene glycol, diethylene glycol, etc. can be used as the low-molecular organic liquid. Among low molecular weight organic liquids, glycerin and propylene glycol are preferred from the viewpoints of enzyme stability, effects on lenses, economy, and performance as a food additive.

The compounding amount of the viscosity modifier in the liquid enzyme agent for contact lenses of the present invention,

It is preferably from 15 to 45 w / w%, more preferably from 20 to 40 w / w%. If the amount of the viscosity modifier is less than 15 wZw%, it may not be possible to keep the viscosity of the enzyme agent low.If it is more than 45 w / w%, the osmotic pressure after the treatment may be increased. The lens may be deformed.

The liquid enzyme agent for contact lenses of the present invention may contain calcium. Calcium contributes to the stabilization of proteolytic enzymes. The content of calcium in the liquid enzyme preparation for contact lenses of the present invention is preferably 0.05 to 0.05 wZw%, more preferably 0.03 wZw%. More preferred. If it is less than 0.05 wZw%, a sufficient enzyme stability effect tends not to be obtained, and if it is more than 0.05 w / w%, the enzyme tends to be unstable.

The liquid enzyme agent for contact lenses of the present invention may contain known auxiliaries such as preservatives, bactericides, pH adjusters (buffers), and / or surfactants. Particularly, the enzyme can be stably present in the liquid enzyme preparation for contact lenses of the present invention or the final preparation of the enzyme preparation, as long as the enzyme preparation of the present invention is not adversely affected on the subject, human body and environment. Not restricted. Further, the amount of each additive is not limited to the following examples, and can be appropriately set by those skilled in the art.

Examples of the preservative include mercury preservatives such as phenylmercuric nitrate, phenylmercuric acetate and thimerosal, surfactant preservatives such as benzalkonium chloride and pyridinium bromide, chlorhexidine, polyhexamethylene biguanide and Alcohol preservatives such as chlorobutanol, methyl paraben, propyl paraben, dimethyl monodimethylhydantoin, imidazolium perrea, boric acid, boric acid compounds or borax can be used. Among them, one or more substances selected from boric acid, boric acid compounds and borax are preferable, and the amount of addition is 0.00000 to 3.0. It is preferably 0 w / w%.

As the bactericide, an organic nitrogen-based bactericide is preferable because of its high bactericidal effect at a low concentration, and among these, a biguanide compound or a derivative thereof (a polymer or salt) is more preferable because of its high safety. Polyhexamethylene biguanide (PHMB) is extremely preferred because it has no absorption or absorption.

Representative examples of the organic nitrogen-based fungicides include, for example, (1) quaternary ammonium compounds or benzalkonium chloride, a polymer thereof, (2) biguanide compounds or their polymers or their salts, such as chlorhexidine dalconate and polyhexamethylene biguanide; and (3) the polymers of the above (1) and (2). It is possible. The amount of the organic nitrogen-based fungicide to be added is about 0.00000001 to 10 w / w%, preferably about 0.00001 to: LwZw%.

Examples of the pH adjusting agent (buffering agent) include boric acid and its sodium salt, phosphoric acid and its sodium salt, citric acid and its sodium salt, lactic acid and its sodium salt, lactic acid and its amino acid such as glutamine, and its sodium salt It is possible to use, for example, rhium salt or malic acid and its sodium salt. The amount of the pH adjuster added is preferably 0.001 to 3.0 wZw%.

As the surfactant, any surfactant such as an anionic surfactant, a nonionic surfactant, or a surfactant composed of an anionic surfactant and a nonionic surfactant can be used. Good.

Examples of anionic surfactants include sodium alkyl sulfate, sodium alkylbenzenesulfonate, sodium alkyl methyl taurine, sodium alkyl sarcosine sodium, one-year-old sodium refine sulfonate, and polyoxyethylene alkyl. Sodium ether phosphate, sodium polyoxyethylene alkyl monodelsulfate, sodium polyoxyethylene alkylphenyl sulfate, sodium di (polyoxyethylene alkyl) phosphate, and the like can be used. The amount of the anionic surfactant added is, for example, 0.01 w / v% or more, preferably 0.02 w / v% or more, and 10 wZv% or less, preferably 5 w / v% or less.

Nonionic surfactants include, for example, polyethylene glycol adducts of higher alkylamines and polyethylene glycols of higher fatty acid amides Adducts, polyglycerol esters of higher fatty acids, polyethylene glycol esters of higher fatty acids, polyalkylene glycols of higher fatty acids, polyethylene glycol copolymers, polyhydric alcohol esters of polyethylene glycol of higher fatty acids, higher Polyethylene glycol ethers of alcohols, polyglycerin ethers of higher alcohols, polyethylene glycol ethers of alkylphenols, formaldehyde condensates of polyethylene glycol ethers of alkylene phenols, polypropylene glycol-polyethylene dalicol copolymers, phosphate esters, Use castor oil, hydrogenated castor oil, polyethylene glycol sorbitan alkyl ester, adduct of sterol with polyethylene glycol, etc. Rukoto can. The addition amount of the nonionic surfactant is, for example, not less than 0.01 w / v%, preferably not less than 0.02 w / v%, not more than 10 wZ v%, preferably not more than 5 w / v%. / v% or less.

When an anionic surfactant and a nonionic surfactant are used in combination, the contents of the anionic surfactant and the nonionic surfactant are within the above ranges, respectively, and the total amount is 0. 0 to 20 w / v%, preferably 0.05 to 10 wZ v%.

In addition, a dye may be added to the liquid enzyme agent for contact lenses of the present invention.

The liquid enzyme agent for contact lenses of the present invention is used after preparing a diluting solution by dropping it into a multi-purpose solution for contact lenses. The multi-purpose solution means a solution that can store, clean, disinfect, and rinse contact lenses in one solution, including a contact lens cleaning preservation solution and a bactericide and a preservative germicide. For example, Ines (Distributor: Menicon Inc.)). By immersing the contact lens in the obtained diluent for a certain period of time, the contact lens adhered to the contact lens. Dirt components such as proteins can be removed without scrubbing.

Hereinafter, the liquid enzyme agent for contact lenses of the present invention will be described in more detail with reference to Examples, but the present invention is not limited to only these Examples.

Examples 1 to 12, Comparative Examples 1 to 16

A liquid enzyme preparation for contact lenses of the present invention (Examples 1 to 12), a conventional enzyme preparation comprising only a water-soluble low-molecular organic liquid and a protease (Comparative Examples 1 to 11), a water-soluble low-molecular organic liquid An enzyme preparation comprising a water-soluble high molecular weight organic solid outside the predetermined content of the present invention and a proteolytic enzyme (Comparative Examples 12 and 13) and an enzyme preparation comprising only a water-soluble high molecular weight organic solid and a proteolytic enzyme (Comparative Examples) Examples 14 to 16) were prepared with the compositions described in Tables 1 and 2.

Example Formulation composition

1 2 3 4 5 6 7 8 Floheren Clicoret 20 20 20 30 0 0 0 0 Glycerin 0 0 0 0 30 20 20 30 3

PEG # 200 * ¹ 0 0 0 0 0 0 0 0

PEG # 1000 "40 0 0 33.5 33.5 20 0 20

PEG # 4000 * ³ 0 40 0 0 0 0 0 0

PEG—Me # 2000 0 0 40 0 0 0 20 0 2

P— NVP # 10000 * ⁵ 0 0 0 0 0 0 0 0 Protease A * ⁶ 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0. Protease B * ⁷ 0 0 0 0 0 0 0 0 Borax 0 0 0 0 0 0 0 0 Dye 0 0 0 0 0 0 0 0 lOmM Tris-HCl (pH = 8.0) Remaining Remaining Remaining Remaining Remaining Remaining Remaining Remaining Remaining water 0 0 0 0 0 0 0 0

Table 2 Comparative example

Composition

1 2 3 4 5 6 7 8 9 10 11 Propylene glycol n π π 20 0 0 0 0 Glycerin 0 0 20 40 60 oo 31.5 36 40.5 45

PEG # 200 * ^λ 0 0 0 0 0 60 40 0 0 0 0

PEG # 1000 * ² 0 0 0 0 0 0 0 0 0 0 0

PEG # 4000 * ³ 0 0 0 0 0 0 0 0 0 0 0

PEG—Me # 2000 * ⁴⁰⁰ 0 0 0 0 0 0 0 0 0 0 Protease A * ⁶ 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0 0 0 0 Protease B * ⁷ 0 0 0 0 0 0 0 2.7 2.7 2.7 2.7 Borax 0 0 0 0 0 0 0 3.3 3.3 3.3 3.3 Dye 0 0 0 0 0 0 0 0.0013 0.0013 0.0013 0.0013 0.

10 mM Tris-HCl (pH = 8.0) Remaining Remaining Remaining Remaining Remaining Remaining Remaining 0 0 0 0 Water 0 0 0 0 0 0 0 Remaining Remaining Remaining Remaining

In Tables 1 and 2, * 1 to * 7 indicate the following.

* 1: Polyethylene glycol (average molecular weight: about 200, liquid, manufactured by Nacalite ³ Disc Co., Ltd.)

* 2: Polyethylene glycol (average molecular weight about 1000, solid, manufactured by Nacalai Tesque, Inc.)

* 3: Polyethylene glycol (average molecular weight about 4000, solid, manufactured by Nacalai Tesque, Inc.)

* 4: Polyethylene glycol monomethyl ether (average molecular weight: about 2,000, solid, manufactured by Aldrich Chemical Co., Inc. any Inc.)

* 5: Polyvinylpyrrolidone (average molecular weight about 10,000, solid, manufactured by Tokyo Chemical Industry Co., Ltd.)

* 6: Cle aLenS -Pro 2.0 L (manufactured by Nopoenzym)

* 7: CL-5 PG (manufactured by Nagase ChemteX Corporation)

In addition, * 1 to * 4 used a titration method, and * 5 used a raw material whose average molecular weight was determined by a viscosity method.

For each enzyme preparation, the residual activity of the proteolytic enzyme, the osmotic pressure measurement test in a multipurpose solution, and the contact lens size change measurement test were performed. Further, for Examples 11 and 12, and Comparative Examples 8 to 13, preservation efficacy tests were also performed.

Test Example 1 (Measurement of residual activity of evening proteinase)

The residual activity of the protease in each of the enzyme preparations of Examples 1 to 12 and Comparative Examples 1 to 7 and 14 to 16 was measured one week and two weeks after the preparation of the enzyme preparation. However, the enzyme preparations of Examples 11 and 12 were measured one week and one month after the preparation of the enzyme preparation. The measurement was performed as follows.

2.0% casein solution (pH 8, 0.05M Tris To 4 mL of an aqueous sodium hydroxide solution, 3.6 mL of a diluent (pH 8, 10 mM aqueous Tris-HCl solution) and 0.4 mL of an enzyme preparation were mixed. Immediately after mixing, 1 mL of the resulting solution was added to 1 mL of a 0.4 M aqueous solution of trichloroacetic acid, and mixed to precipitate undegraded casein. This operation was performed three times to obtain three samples (n = 3). The initial absorption values at 280 nm due to the casein hydrolyzate in each supernatant were measured, and the average value A of the three initial absorption measurement results. I asked. The remaining 5 mL was kept at 37 ° C. for 10 minutes, and undegraded casein was precipitated using the 1 mL by the precipitation method described above. This operation was performed four times to obtain four samples (n = 4). The absorption value after treatment at 280 nm in each supernatant was measured, and the average value A of the four absorption results after treatment was determined. Initial absorption average value A from absorption average value A after treatment. The value after subtraction was used as the activity value of evening proteinase.

The residual activity (%) was calculated by the following equation.

Residual activity value (%) = [(AA ₀ ) / A _Day . ] X 100

A _Day0 : Enzyme activity value on test start day

Tables 3 and 4 show the residual activity value of the enzyme in each enzyme preparation.

Table 3 Examples

Period

4 6 7 8 9 10 12

One week later 87 85 95 94 91 84 100 100 100 100 95 93

2 weeks later

Or 93 85 94 91 90 80 100 100 100 96 87 92 1 month later

Unit (%) Table 4

Unit (%) As is clear from Tables 3 and 4, the water-soluble high-molecular organic solid exhibits sufficient enzyme activity stabilizing action, and is almost equivalent to the enzyme activity stabilizing action of the water-soluble low-molecular organic liquid. There was found. It was also found that a sufficient stabilizing effect was obtained even when the water-soluble high-molecular organic solid and the water-soluble low-molecular organic liquid were mixed in various ratios.

Test example 2 (Osmotic pressure measurement test in multi-purpose solution)

The contact lens enzymatic agents of Examples 1 to 9, 11 and 12, and Comparative Examples 1 to 7 and 14 to 16 were respectively added to a multipurpose solution, and the osmotic pressure of the solution was measured.

As a multi-purpose solution, Ines (manufacturer: Menicon Co., Ltd.) was used, and 2 L of Ines was added to each of the enzyme preparations in an amount of 80 L (2 drops). HOSM-1 (TOA Electronics Ltd.) was used for the osmotic pressure measurement.

Tables 5 and 6 show the osmotic pressure of each solution. Table 5

Unit (m〇 sm / kg), Ines; 293mO sm / kg Table 6

Unit (mO sm / kg), Ines; 293mO sm / kg Enzyme is diluted 26-fold (80 L / 2 mL), which is small in total, but as evident from Tables 5 and 6, It was confirmed that when a large amount of propylene glycol or dalyserin was contained, the osmotic pressure was significantly increased. On the other hand, when a large amount of the water-soluble high molecular organic solid was contained, the osmotic pressure was clearly lower than those.

Test example 3 (DIA change measurement test of contact lens)

The degree of swelling of the lens when continuously immersed in each of the enzyme agents for a certain period was measured. The measurement was performed as follows.

A treatment solution was prepared by mixing 2 L of Ines with 80 L of enzyme (equivalent to 2 drops). Next, a contact lens was immersed in each treatment solution. The enzyme preparations of Example 3 and Comparative Example 1 were 1 day and 3 days after the immersion, and the enzyme preparations of Examples 11 and 12 and Comparative Examples 3, 4 and 5 were 1 day after the immersion. Four days later, and for the enzyme preparations of Examples 1, 2, 4, 5, 6, 7, 8 and 9, and Comparative Examples 2, 6, 7, 14, 15 and 16, 1 day and 5 days after immersion After a day, the diameter (DIA) of the contact lens was measured. In the test, a frequently interchangeable lens Accuview-1 (manufactured by Johnson & Johnson, water content 58%) was used, and the treatment solution was changed once daily. In DIA measurement, the diameter (A) is measured using the marking on the contact lens as an index, and then the diameter (B) perpendicular to the diameter (A) is measured. Average of diameter (A) and diameter (B) Was taken as the DIA measurement value.

Tables 7 and 8 show the results of comparing the measured DIA values of the processed lens with those before the processing. Table 7

Single (mm) Table 8

Unit (mm) As is clear from Tables 7 and 8, it was found that when a large amount of water-soluble low-molecular-weight organic liquid is contained, the lens swells (deforms) significantly. However, it was found that swelling (deformation) did not occur when a large amount of water-soluble organic polymer solid was contained. Interestingly, it was found that polyethylene glycol (liquid) with an average molecular weight of about 200 swells (deforms) the lens, but that deformation can be suppressed above 100,000.

Test example 4 (viscosity comparison test of liquid enzyme preparation for contact lens)

Each of the enzyme preparations of Examples 1 to 9, 11 and 12 and Comparative Examples 1 to 7 and 14 to 16 was placed in a glass container and capped. Then reverse the container The falling state of the enzyme solution when it was cooled was visually observed, and the viscosity of each enzyme solution was compared. The results are shown in Tables 9 and 10. Table 9

Table 10

酵素 Enzyme solution that immediately falls when the container is turned upside down.

△ Enzyme solution that passed down the container within 1 second when the container was turned upside down.

X Enzyme solution that does not fall even after 1 second when the container is turned upside down.

With respect to Examples 1 to 9, 11 and 12 and Comparative Examples 1 to 7 and 14 to 16, the effects of each enzyme preparation were comprehensively evaluated based on the results of Test Examples 1 to 4. . Each evaluation is shown in Tables 11 and 12. Example

Effect

1 2 3 4 5 6 7 8 9 1 1 1 2

(A) 〇〇〇〇〇〇〇〇〇〇〇

(Ii) 〇〇〇 Δ 〇〇〇 Δ △ Δ Δ

(ゥ) 〇〇〇〇〇〇〇〇〇〇〇

(D) 〇〇〇〇〇〇〇〇〇〇〇 Overall evaluation ◎ ◎ ◎ 〇 ◎ ◎ ◎ 〇〇〇〇〇

Two

(A), (a), (、), and (e) in Tables 11 and 12 and the respective symbols are as follows.

In addition, common to each of the items (a) to (e), each symbol is: 〇: Preferred as a liquid enzyme agent for contact lenses, Δ: Degree of use as a liquid enzyme agent for contact lenses, X : Not suitable as liquid enzyme preparation for contact lenses.

(A) Measured degree of lens swelling (based on the results in Tables 7 and 8)

サイズ The change in size before and after lens immersion is 0.05 mm or less

△ Change in size before and after lens immersion is greater than 0.05 mm and 0.10 or less

X Change in size before and after immersion is greater than 0.10 mm (B) Measured osmotic pressure increase (based on the results in Tables 5 and 6) 浸透 Osmotic pressure is 450 m〇 smZkg or less

Δ Osmotic pressure is greater than 45 OmOsmZkg and 50 OmOsmZkg or less X Osmotic pressure is 500 m〇 greater than sm / kg

(Ii) Stability of enzyme activity after 2 weeks or 1 month (based on the results in Tables 3 and 4)

〇 80% or more

△ 60% or more and less than 80%

X less than 60%

(E) Viscosity comparison (based on the results in Tables 9 and 10)

◎ All items are 〇. Such enzyme preparations are highly preferred as liquid enzyme preparations for contact lenses.

場合 At least one item is a △ and the remaining items are 〇. Such enzyme agents are preferred as liquid enzyme agents for contact lenses.

X if at least one item is X. The corresponding enzyme preparation is not suitable as a liquid enzyme preparation for contact lenses.

From the results of Test Examples 1 to 4 and the comprehensive evaluations shown in Tables 11 and 12, it was confirmed that the examples were effective as liquid enzyme preparations for contact lenses. Here, in order to confirm the further effectiveness of the examples, the following tests were performed using the enzyme preparations of Examples 11 and 12 and Comparative Examples 8 to 13. Test Example 5 (Preservation efficacy test)

Five types of bacterial suspensions of Pseudomonas aeruginosa IFO 13275, Staphylococcus aureus IFO 13276, Escherichia coli IFO 3972, Candida albicans IFO 1594, and Aspergillus niger ATCC 16404 were prepared as test bacteria. As test samples, the enzyme preparations of Examples 11 and 12 and Comparative Examples 8 to 13 were used. 100 L of the bacterial suspension was inoculated to 10 mL of the test sample dispensed into the tube and mixed. Each test sample inoculated with the bacteria was placed in 22 incubators overnight and cultured. To measure the number of inoculated bacteria, a saline solution inoculated with the bacteria (prepared separately) was serially diluted 10-fold with physiological saline, and Aspergillus niger was spread on the medium (bacteria: SCD LP, fungi: SDLP). Others were pruned. S CD LP medium at 32 ± 2 for 6 days, 30? The medium was cultured at 22 ± 2 ° C for 5 days (3 per group). On the 14th day after inoculation, 0.5 mL was collected from the test sample inoculated with the bacteria, serially diluted 10-fold with physiological saline to determine the number of viable bacteria, and placed in a medium (bacterial: SCDLP, fungus: SDLP). Surgirus Niger was smeared and the others were poured. 3〇0? The medium was cultured at 32 soil 2 for 6 days, and the SDLP medium was cultured at 22 ± 2 ° C for 5 days (3 per group). After completion of the culture, the number of colonies was counted, and the number of viable bacteria in the sample was calculated from the average value of the three colonies. However, plates of 300 cfu / plate or less for bacteria and plates of 100 cfu / plate or less for fungi are used.Log reduction = 1 og (inoculated bacteria) (Number of bacteria on the 14th day). Table 13 shows the results. Table 13 Example Comparative Example

11 12 8 9 10 11 12 13

Pseudomonas aeruginosa

> 4.98> 4.98> 5.09> 4.79> 4.79> 4.79> 5.09> 5.09

I FO 13275

Staphylococcus aureus

> 5.10> 5.10 0.93 2.37 2.30 2.29 1.02 2.02

I FO 13276

b E. coli

> 5.04> 5.04 3.26 2.89 3.60 4.03 2.29 3.00

I FO 3972

Candida Albicans

2.85 5.26 0.34 0.88 0.82 0.69 0.78 1.25

I FO 1594

Aspergils Niger

2.08 1.04 2.83 2.04 1.76 1.64 2.78 2.75

ATCC 16404

As is clear from Table 13, Examples 11 and 12 show that the log reduction is 4 or more for all bacteria and 1 or more for all fungi, It was confirmed that it was excellent. On the other hand, in Comparative Examples 8 to 13, none of Examples 11 and 12 obtained a log reduction of 4 or more for all bacteria and 1 or more for all fungi. . The largest difference in the composition between the Example and Comparative Example in Test Example 5 is the amount of PEG # 100, and it is possible that the amount of PEG # 100 may have contributed to the storage efficiency of the formulation. The finding was very high. Industrial applicability

The water-soluble high molecular organic solid contained in the liquid enzyme agent for contact lenses of the present invention is not taken up by the contact lens and does not have any adverse effect such as swelling of the lens. Therefore, the liquid enzyme agent for contact lenses of the present invention does not impair the lens function. In addition, the liquid enzyme preparation for contact lenses of the present invention can prevent an increase in the osmotic pressure of the treatment liquid when the enzyme preparation is dropped, and can suppress adverse effects on the lens and eye irritation during misuse. Furthermore, the liquid enzyme preparation for contact lenses of the present invention has the same enzyme activity stabilizing action as the conventional liquid enzyme preparation for contact lenses (water-soluble low-molecular organic liquid + proteolytic enzyme).

As described above, the liquid enzyme agent for contact lenses of the present invention has a very excellent effect.

Claims

Scope of Word

1. A liquid enzyme preparation for contact lenses containing a water-soluble organic polymer solid having an average molecular weight of 800 to 1000, a viscosity modifier and an enzyme.

2. The liquid enzyme agent for contact lenses according to claim 1, wherein the water-soluble organic polymer solid is a polyalkylene dalicol.

3. The liquid enzyme agent for contact lenses according to claim 1, wherein the water-soluble high molecular organic solid is polyethylene glycol or polyethylene glycol monomethyl ether.

4. The liquid enzyme agent for a contact lens according to claim 1, wherein the water-soluble polymer organic solid is contained in an amount of 5 to 45 wZw%.

5. The liquid enzyme agent for contact lenses according to claim 1, wherein the viscosity modifier is a water-soluble low molecular weight organic liquid.

6. The liquid enzyme agent for contact lenses according to claim 1, wherein the viscosity adjusting agent is contained in an amount of 15 to 45 w / w%.