JPH11116991A - One-pack type liquid formulation for contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a one-pack type liq. formulation for a contact lens which possesses good detergency against protein and fat stains and soils and long-term stability at room temp. and can also be used as a stock liq. by incorporating a protease, a nonreducing polyhydric alcohol, an anionic surfactant, and a buffer. SOLUTION: This one-pack type liq. formulation comprises: 10 to 1,000 PU/ml protease (A) comprising a serine protease produced from microorganisms or an animal-derived serine protease; 10 to 45 g/100 ml nonreducing polyhydric alcohol (B) selected from among glycerol, propylene glycol, ethylene glycol, mannitol, sorbitol and the like; 0.001 to 0.75 g/100 ml anionic surfactant (C) selected from among alkyl or olefinsulfonic acids, ethercarboxylic acids, alkylphosphoric acids, N-acylamino acids and the like, and alkali metal salts thereof; and a buffer (D) comprising a combination of a tris(hydroxy 1-2C alkyl) aminomethane with borax.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a one-part liquid composition for contact lenses. More specifically, the present invention relates to a one-part liquid composition which is stable for a long time at room temperature and has a storage effect for cleaning contact lenses.

[0002]

2. Description of the Related Art Contact lenses are roughly classified into hydrous contact lenses and non-hydrous contact lenses. The present invention is generally directed to what are referred to as hard contact lenses and oxygen permeable contact lenses, and to non-hydrous soft contact lenses.

[0003] By the way, contact lenses are hydrated,
Regardless of non-water content, when worn on the eyes, proteins derived from tear components and lipids derived from eye oils, etc. adhere to contact lenses. It is necessary to ensure a good field of view when re-wearing.

Therefore, conventionally, a daily treatment using a detergent containing a surfactant is carried out for lipid stains, and a tablet containing proteolytic enzyme is further treated about once a week for protein stains. Was used to perform the processing. However, such lens care has a high risk of being messy and omitted. In order to eliminate such danger,
In recent years, research on stabilization methods of proteolytic enzymes in solution has been promoted in pursuit of simpler contact lens care methods, and along with this, various detergents that provide proteolytic enzymes in liquid form have been launched. ing.

[0005] Specifically, Patent No. 26 proposes to include a proteolytic enzyme in a preservation solution for contact lenses.
No. 03491 is known. The formulation proposed by this patent is:
It contains a water-soluble polymer containing a quaternary ammonium group and a hydroxyl group, and a protease derived from a microorganism, and further contains a preservative.

Further, a liquid enzyme type contact lens cleaning solution is disclosed in Japanese Patent Publication No. Hei 5-77047 and Japanese Patent Laid-Open No.
It is proposed in 3919 gazette. The former contains a solution having a mixing ratio of water-miscible organic liquid and water of 50:50 to 75:25 and a protease, and the latter contains a polyhydric alcohol and Bacillus subtilis of 20% by weight or more. A cleaning solution for contact lenses, comprising a liquid culture-derived proteinase. These require a dilution operation in order to express the enzyme activity, and the washing effect is not sufficient at a practical level.

[0007] Further, a one-pack type preparation of a hard contact lens has been proposed in JP-A-7-146454. That is, it is a solvent for contact lenses characterized by containing a pyrrolidone compound and a proteolytic enzyme, which also has a cleaning effect when a preparation ready for use (solid preparation or two-part preparation) is used. Was not as good as the detergency.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to provide a one-part liquid composition for contact lenses. Another object of the present invention is to provide a one-part liquid composition suitable as a contact lens cleaner showing a good cleaning effect on protein stains and fatty stains. Still another object of the present invention is to provide a one-part liquid composition containing a protease which enables a simple method of contact lens care and contains a protease which is stable at room temperature for a long period of time. It is still another object of the present invention to provide a one-part liquid composition for contact lenses that can be used as a preservative.
Still other objects and advantages of the present invention will become apparent from the following description.

[0009]

According to the present invention, the above objects and advantages of the present invention are as follows: (A) 10 to 1,000 PU / ml of protease (B) 10 to 45 g / 100 m of non-reducing polyhydric alcohol
l (C) anionic surfactant 0.001 to 0.75 g / 10
It is accomplished by 0ml and (D) tris (hydroxymethyl C ₁ ~ ₂ alkyl) amino methane and contact lens one-liquid composition characterized by containing a buffering agent consisting of a combination of borax.

[0010] In the present invention, a protease is used to remove protein stains. Examples of the protease include a serine protease derived from a bacterium belonging to the genus Bacillus, trypsin and chymotrypsin derived from an animal, a serine protease derived from the genus Streptomyces of the actinomycete, and a serine protease derived from the genus Aspergillus of the filamentous fungus. Alternatively, a serine protease whose stability has been further improved by genetic manipulation may be used. Among the above-mentioned serine proteases, serine proteases derived from the genus Bacillus are particularly desirable, and examples thereof include "bioprase" (Nagase Seikagaku Corporation), "alcalase", "esperase", "sabinase", and "subtilisin A". "," PEM "(Novo Industry Japan Co., Ltd.)," Protease N "Amano""," Protease P "Amano""," Protease S "Amano""
(Amano Pharmaceutical Co., Ltd.) "Actinase" (Kaken Pharmaceutical Co., Ltd.) and the like.

In the composition of the present invention, the concentration of serine protease is 10 to 1000 PU / m as the activity of the enzyme.
l (PU is the unit of protein digestion).
Further, it is preferably 200 to 400 PU / ml. The PU in the present invention is basically a unit obtained when the reaction conditions are measured at 30 ° C. in accordance with the digestion test method (2) described in the Japanese Pharmacopoeia General Test Method. One of the outstanding features of the present invention is that it enables long-term room temperature stability against low concentrations of serine protease.

In the composition of the present invention, in addition to the above-mentioned protease, a glucolytic enzyme or a lipolytic enzyme can be used in combination. In some cases, papain,
A cysteine protease such as promelain or a metal protease such as thermolysin can also be used in combination.
In such a case, an auxiliary agent such as a reducing agent or a metal ion is required, so that attention must be paid to the enzyme used.

The composition of the present invention contains a non-reducing polyhydric alcohol and an anionic surfactant as a stabilizer and an activator of a protease such as a serine protease, respectively. The present invention can be achieved only when there is interaction of at least these three preparations.

Examples of the non-reducing polyhydric alcohol include glycerin, propylene glycol, polypropylene glycol, ethylene glycol, polyethylene glycol, sorbitol, mannitol, polyvinyl alcohol and the like. Among them, glycerin, propylene glycol and the like, which have been proven as food additives, are particularly preferable. The concentration of the polyhydric alcohol to be blended is 10 to 45 g per 100 ml of the liquid composition.

Examples of the anionic surfactant include sulfonic acid, carboxylic acid, phosphoric acid, N-acylamino acid, N-acyltaurine and alkali metal salts thereof. These may be used alone or in combination of two or more. As the alkali metal salt, for example, a sodium salt, a potassium salt, and a magnesium salt are preferably used. Specific examples include α-olefin sulfonate, alkyl sulfonate, alkylbenzene sulfonate, carboxylated ether salt having polyoxyethylene chain, alkyl phosphate, alkyl ether phosphate having polyoxyethylene chain / Sulfates, alkyl sulfates, alkyl sulfate ethers, alkyl sarcosine salts,
Alkyloyl methyl taurine, alkyloyl benzalcosin and the like. Among them, α-olefin sulfonate is particularly effective as a stabilizing and activating agent for serine protease. The concentration of the anionic surfactant is 0.001 to 0.75 g per 100 ml of the liquid composition.
It is. Such a low concentration of the anionic surfactant contributes to stabilization of the serine protease. As described above, in the present invention, since an anionic surfactant is blended as a stabilizer and an activator for serine protease, a good cleaning effect can be simultaneously exhibited on fat stains in addition to protein stains. Become. The concentration of the anionic surfactant is preferably 0.01 to 0.20 g / 100 m
l.

The liquid composition of the present invention may contain a nonionic surfactant, an amphoteric surfactant and the like in addition to the anionic surfactant. Examples of nonionic surfactants include polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene sorbitan alkyl ester, polyoxyethylene hydrogenated castor oil, Examples include fatty acid monoglycerides, propylene glycol fatty acid esters, fatty acid sucrose esters, polyoxyethylene-polyoxypropylene ethylene diamine condensates, and the like.

Examples of amphoteric surfactants include N-lauroylaminopropyl-N, N-dimethylglycine, N-
Cocoylaminopropyl-N-hydroxyethylglycine, N-3-dodecyl-2-hydroxypropyl-N,
N-dimethylglycine, N-cocoylaminopropyl-
N-hydroxyethyl-3-aminopropionic acid and the like.

Since the composition of the present invention contains the above-mentioned three components as essential components, the composition exhibits a sufficient preservative effect without adding a preservative separately. In general, some of the preservatives can contribute to ophthalmologic disorders, so that it was possible to provide a liquid preparation showing a sufficient preservative effect without adding a preservative,
This is one of the further excellent features of the present invention.

The liquid compositions of the present invention is a combination of tris (hydroxy C ₁ ~ ₂ alkyl) amino methane and borax is used more as a buffering agent. Tris (hydroxy C _1
1-2 alkyl) tris amino methane (hydroxymethyl) aminomethane or tris (hydroxyethyl)
Means aminomethane. These can be used alone or together. This buffering agent is less irritating to the eyes when using the liquid composition for contact lenses, and is particularly excellent for activating serine protease. The pH of the liquid composition of the present invention is preferably in the range of 6 to 8. Boric acid, hydrochloric acid, sodium (or potassium) dihydrogen phosphate, disodium (or potassium) monohydrogen phosphate, sodium acetate, triethanolamine and the like are appropriately added so as to fall within the above range. Can be used in combination. The liquid composition of the present invention,
Further, a chelating agent or the like can be contained as needed.

The chelating agent is used for the purpose of, for example, removing a complex of a protein and an inorganic salt such as calcium in the tear fluid attached to the lens surface. Specifically, ethylenediaminetetraacetic acid, gluconic acid, citric acid, tartaric acid,
Examples thereof include diethylenediaminepentaacetic acid and their sodium or potassium salts, sodium polyphosphate, sodium nitrilotriacetate and the like. Among them, disodium ethylenediaminetetraacetate is particularly preferred.

However, it is known that a metal chelating agent extremely lowers the stability of serine protease. Therefore, great care must be taken when compounding the chelating agent.

In the present invention, the mixing ratio is such that the protease exhibits a sufficient washing effect even at a low concentration, and the essential components incorporated for stabilizing and activating the protease exhibit a good storage effect. Therefore, it was clarified that not only the function as a washing solution that does not require a dilution operation, but also the function as a preservation solution is guaranteed.

Hereinafter, several embodiments of the present invention will be described.
The present invention is specifically disclosed. However, they are intended to illustrate the invention and do not limit the scope of the invention.

[0024]

【Example】

Example 1 At the mixing ratio shown in Table 1, each component was dissolved in about 80 ml of purified water.
7 was prepared for each sample. Using each sample immediately after preparation, the cleaning effect on the artificially stained oxygen-permeable hard contact lens (hereinafter referred to as artificial stain lens) and the residual enzyme activity after storage at 40 ° C. for one week were measured. evaluated.

The artificial soil lens is obtained by immersing an oxygen-permeable hard contact lens in an artificial soil model solution consisting of egg white lysozyme, ovalbumin, fat and mucin. Was prepared and fixed. Next, using a lens case for hard contact lenses containing each sample until about the 9th minute,
The artificially soiled lens was immersed for 4 hours. After immersion, the artificially stained lens is lightly rinsed with tap water and then immersed in erythrosin solution.
It was immersed for about 0 seconds, lightly rinsed again with tap water, excess erythrosin solution was removed, the stain remaining on the lens was reacted with the red pigment of erythrosin, and the area was used for visual evaluation. At the time of visual observation, 5 points where the dirt was completely removed, 4 points where the dirt was removed about 80%, 3 points where the dirt was removed about 50%, The evaluation criteria were based on a five-point scale in which two points were removed when only about 20% of the dirt was removed, and one point when dirt was barely removed. For each sample solution, the measurement was performed using five artificially soiled lenses, and the average value was obtained. When a number after the decimal point occurred, the number from 1 to 5 rounded off was used as the evaluation point.

The enzyme activity was measured in accordance with the digestion test method (2) described in the 13th revised Japanese Pharmacopoeia General Test Method.
The measurement was performed at 0 ° C., and the value was obtained by the equation (1). Furthermore, the residual activity (%) was expressed as a relative activity with the enzyme activity at the start of storage being 100%, as shown in equation (2). Formula (1): Enzyme activity (PU / ml) = absorbance of sample / absorbance of standard tyrosine × 10 × dilution factor Formula (2): Residual enzyme activity (%) = enzyme activity after storage / enzyme activity at start of storage × 100

[0027]

[Table 1]

As shown in the results of Table 1, the solution 1 showed good results in both the cleaning effect and the preservation of the enzyme, but Comparative Example 1 had poor preservation of the enzyme and Comparative Example 2 had poor cleaning effect. It was a result. In Comparative Example 3, both the cleaning effect and the preservability of the enzyme were not so good.

Example 2 Each component was dissolved in about 80 ml of purified water at the mixing ratio shown in Table 2, and finally the total amount was 100 ml and the pH was 100%.
Was 7 so that each sample was prepared. Using such samples, the washing effect immediately after preparation of each sample solution and the residual enzyme activity after storage at 40 ° C. for one week were measured and evaluated. From the solution 2 to the solution 9, the washing effect and the preservability of the enzyme were all good.

[0030]

[Table 2]

Example 3 Using the solutions 1, 2 and 3 shown in Tables 1 and 2 and the comparative solution 4 consisting of physiological saline, the 13th revised Japanese Pharmacopoeia Reference Information 4. The preservative efficacy was evaluated according to the preservative efficacy test method. Table 3 shows the results of the preservation efficiencies on the 7th and 14th days of each sample solution after adding the bacteria. The bacteria used for the test were
E. coli, P. aerugino
sa) and S. aureus 3
Bacterial species and fungi were carried out using two species of yeast (C. albicans) and black mold (A. niger). Table 3
As shown in Table 2, the solutions 1 to 3 showed good preservative effect, but the comparative example 4 showed almost no preservative effect.

[0032]

[Table 3]

[0033]

As is apparent from the above description, the one-part liquid composition for contact lenses of the present invention has a synergistic effect of a protease, a non-reducing polyhydric alcohol, an anionic surfactant and a specific buffer. This enables long-term stability of the protease at room temperature, exhibits good detergency against proteins and fat stains, and has a sufficient storage effect for use as a storage solution. For this reason, it has become possible to provide a one-pack type washing / preserving solution that does not require a dilution operation. When using the present invention, after filling the product of the present invention to about 90% of the commercially available lens case,
It is very simple that a sufficient washing and preserving effect can be obtained only by leaving it for a long time.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C11D 3:30) (72) Inventor Atsushi Matsumoto 156-5 Kamimidai, Toyooka, Hyogo Pref. Offtex Research Institute, Inc. (72) Inventor Hiroaki Miichi 156-5 Kamimidai, Toyooka City, Hyogo Pref.

Claims (4)

[Claims] (A) Protease 10 to 1,000 P
U / ml (B) Non-reducing polyhydric alcohol 10-45 g / 100 m
l (C) anionic surfactant 0.001 to 0.75 g / 10
0ml and (D) tris (hydroxymethyl C ₁ ~ ₂ alkyl) amino methane and a buffering agent for contact lenses one-liquid composition characterized by comprising a comprising a combination of borax. 2. The liquid composition according to claim 1, wherein the protease is a microbial serine protease or an animal-derived serine protease. 3. The non-reducing polyhydric alcohol is glycerin,
The liquid composition according to claim 1, which is selected from the group consisting of propylene glycol, ethylene glycol, polyethylene glycol, polyvinyl alcohol, mannitol, and sorbitol. 4. The method according to claim 1, wherein the anionic surfactant is at least one selected from the group consisting of alkyl or olefin sulfonic acids, ether carboxylic acids, alkyl phosphoric acids, N-acyl amino acids, N-acyl taurines, and alkali metal salts thereof. 2. The liquid composition according to claim 1, comprising a seed.