JP2603491B2 - Hard contact lens preservative - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a hard contact lens preservation solution containing a protease derived from a microorganism.

Conventional technology Hard contact lenses containing polymethyl methacrylate as a main component have easy workability such as cutting and polishing, good dimensional stability, mechanical strength, transparency, etc., and are easy to clean. It has been widely used because it has advantages such as good storage stability.

However, the need for oxygen supply to the cornea from the physiological aspect of the cornea has been debated, and this type of hard contact lens, which has extremely low oxygen permeability, needs to be improved, and various dimethylsiloxane groups and An oxygen-permeable hard contact lens using a material containing a fluorine atom has been developed.

These oxygen permeable hard contact lens surfaces
The surface energy is smaller than that of a normal hard contact lens, the affinity with tears is poor, and dirt tends to adhere to the lens surface. It is considered that this adhesion of dirt is due to the protein or the like in the tear fluid being easily adsorbed on the lens surface or the adsorbed protein being easily denatured on the lens surface.

If the contact lens gets dirty, the lens may become cloudy, damage the cornea, cause redness, etc.
In some cases, the mounting must be stopped.

Therefore, removal of dirt is very important and indispensable from the viewpoint of safety of contact lenses. For this reason, those using a surfactant, those using an oxidizing agent, those using an enzyme, etc. are commercially available as contact lens cleaning agents, but contact lenses are washed with these cleaning agents, and then supplied with tap water, After rinsing with a physiological saline solution, it is desirable to store the lens surface in a preservative solution in order to maintain the hydrophilicity of the lens surface and store it hygienically.

For cleaning and storing contact lenses, a predetermined cleaning solution and a preserving solution are required, respectively. Since cleaning with an enzyme does not adversely affect the contact lens and has a relatively high effect of removing dirt, it is often used for cleaning oxygen-permeable hard contact lenses made of a material having a small surface energy.

However, the conventional method of using an enzyme detergent often cannot completely remove dirt even if the lens is washed with a detergent containing a surfactant as a main component.
The dirt is removed by immersing the enzyme-containing tablet in a solution in which the enzyme is dissolved.However, in this method, dirt that cannot be removed with an enzyme detergent is further removed every month by a chemical oxidizing agent that uses a chemical oxidizing action. Must be removed by immersing the lens in the lens.

In addition, when the enzyme detergent is left in a solution state for a long time, the enzyme activity is reduced, and the cleaning effect is reduced.
Immediately before use, a solid or powdery enzyme detergent must be dissolved and used, and the operability is poor.

Furthermore, it is desirable to store the contact lens in the preservation solution in order to maintain the hydrophilicity of the lens surface and keep it hygienic even with the contact lens which has been washed with the enzyme detergent and the detergent having an oxidizing effect. Contact lenses are stored in a preservative solution for nearly 8 to 12 hours a day.

Therefore, it is possible to remove dirt from the lens during storage of the lens, to maintain the hydrophilicity of the lens surface, and to use an oxidizing agent that has a risk of adversely affecting the complicated cleaning operation and the lens material as described above. There is a strong demand for the development of a contact lens preservation solution that can reduce the frequency of the contact lens preservation.

Therefore, Japanese Patent Publication No. 53-47810 and Japanese Patent Application Laid-Open No. 58-209713
Japanese Patent Application Laid-Open Publication No. Sho 60-12147 and the like have attempted to improve enzyme-containing detergents, all of which have a high stain removal effect, but are not capable of maintaining the effect over a long period of time in a solution state. It is difficult, and the effect of maintaining the hydrophilicity of the lens surface is small.

Problems to be Solved by the Invention The present invention stores enzyme-permeable hard contact lenses containing dimethylsiloxane groups and fluorine atoms in a protease-containing solution derived from microorganisms, and removes dirt attached to the lenses without heating. Another object of the present invention is to provide a hard contact lens preservation solution that can enhance the hydrophilicity of the lens surface at the same time and maintain the protease activity in the protease-containing solution for a long period of time.

Means for Solving the Problems The present invention provides a solution containing a protease derived from a microorganism,
By containing a water-soluble polymer having a quaternary ammonium group and a hydroxyl group, proteinaceous films and debris can be effectively removed from the contact lens surface, and the activity of protease can be stably maintained in a liquid state for a long period of time. Keep,
In addition, it has been found that the hydrophilicity of the lens surface can be enhanced.

The preservation solution of the present invention is particularly effective as a preservation solution for an oxygen-permeable hard contact lens containing a dimethylsiloxane group or a fluorine atom.

Typical examples of the microorganism-derived protease used in the present invention include those obtained from Bacillus and Streptomyces bacteria and Aspergillus fungi, but commercially available proteases may be used. These are rarely obtained in a pure form and often contain amylase and / or a small amount of lipase.

The present invention provides a protease derived from such a microorganism at pH
About 6.5 to 7.4 neutral buffer such as sodium citrate or gallium-citrate, boron-sodium borate,
0.001 for sodium bicarbonate and Na ₂ HPO ₄ -KH ₂ PO ₄
Suitably it is dissolved in a solution of from 10% to 10% by weight, preferably from 0.01% to 5% by weight.

The water-soluble polymer having a quaternary ammonium group and a hydroxyl group used in the present invention is a reaction product of a water-soluble polymer having a hydroxyl group and a glycidyltrialkylammonium halide. This reactant gives the protease solution an action of maintaining the protease activity in a liquid state for a long period of time and increasing the hydrophilicity of the oxygen-permeable hard contact lens surface. For example, chlorotrimethylammonium-2- Hydroxypropyl-hydroxyethylcellulose, chlorotriethylammonium-2-hydroxypropyl-hydroxyethylcellulose, chlorotrimethylammonium-2-hydroxypropyl-hydroxyisopropylcellulose, chlorotrimethylammonium-2-hydroxypropyl-dextran, chlorotrimethylammonium-2-hydroxypropyl −
Pullulan, chlorotrimethylammonium-2-hydroxypropyl-polyvinyl alcohol, chlorotrimethylammonium-2-hydroxypropyl-polyglycerin, chlorotrimethylammonium-2-hydroxypropyl-dextrin, chlorotrimethylammonium-2-hydroxypropyl-cyclodextrin, etc. It is preferable to use a reaction product of a hydroxyl group-containing water-soluble polymer and glycidyl trialkyl ammonium halide. The content of the water-soluble polymer is preferably from 0.1% by weight to 2.0% by weight, particularly preferably from 0.5% by weight to 1.0% by weight based on the total amount of the liquid.

The content of the quaternary ammonium group contained in the water-soluble polymer is 0.1% by weight or less as a nitrogen atom content.
It is preferably 3.0% by weight, especially 0.1% to 2.0% by weight.

When the quaternary ammonium group content is increased, the effect of increasing the hydrophilicity of the oxygen-permeable contact lens surface is enhanced, but the protease activity tends to decrease. Conversely, when the quaternary ammonium group content decreases (for example, when the nitrogen atom content is 0.1% by weight or less), the effect of increasing the hydrophilicity of the oxygen-permeable hard contact lens surface decreases.

The protease solution of the present invention preferably contains a neutral or nonionic surfactant in order to lower the interfacial tension between the lens surface and the protease solution when the lens is immersed and to improve familiarity, for example, polyethylene glycol alkyl. It is preferable to use ether, polyethylene glycol alkyl ester, etc. in a range of 0.5% by weight or less.

Preservatives such as sorbate, 1,5-pentanediol, alkyltriethanolamine and the like can be added to the preservative solution of the present invention as needed at 0.001% to 0.1% by weight. Also, to weaken the action of metal ions, such as calcium ions, contained in protein stains,
A chelating agent may be contained, and as the chelating agent,
For example, tetrasodium salt and disodium salt of ethylenediaminetetraacetic acid are preferably used at a ratio of 0.01% by weight to 0.5% by weight.

Hereinafter, the present invention will be described in more detail with reference to Examples.
The measured values in the examples were measured by the following methods.

Protease activity preservation rate: Protease activity can be determined by a known method using casein digestion (eg, Journal of General Phyalology 30 (1947) 2).
91).

Stain removal rate: An artificial protein solution having the following composition substantially similar to that of tear fluid was prepared.

Albumin (derived from egg) 1.44% γ-globulin (bovine serum) 0.42% Lysozyme 0.36% Remaining physiological saline Immerse an oxygen-permeable hard contact lens containing dimethylsiloxane groups and fluorine atoms in this protein solution. The protein was denatured by heating to 60 ° C. while the lens was immersed, and artificial protein stain was attached to the lens surface. Next, the lens to which the artificial stain was attached in this manner was stained with erythrosine, which specifically stains a protein, and the spectrophotometer (Hitachi Model 100-10 manufactured by Hitachi, Ltd.) was used.
The absorbance at 545 nm was measured using a mold. The absorbance at this time is defined as A. Separately, the lens to which the artificial protein stain was adhered was immersed in a protease solution for a predetermined time, washed with water, stained again with erythrosine, and measured for absorbance at 545 nm using a spectrophotometer. The absorbance at this time is B.

Contact angle: A small water drop was dropped on the lens surface, and the contact angle of the water drop was measured using a contact angle meter manufactured by Kyowa Kagaku.

Hydrogen ion concentration of protease solution: Measured using a pH meter manufactured by Toyo Kagaku Sangyo Co., Ltd.

Example 1 After dissolving 2.0 g of a protease derived from a filamentous fungus in 98 ml of a phosphate buffer having a pH of 7.0 and 0.1 N, chlorotrimethylammonium-2-hydroxypropyl having a nitrogen atom content of a quaternary ammonium group of 1.0% by weight was dissolved. 0.5 g of hydroxyethyl cellulose, 0.01 g of polyoxyethylene glycol lauryl ether as a nonionic surfactant, and 00.01 g of potassium sorbate were added and dissolved at room temperature. Immediately after the protease activity was measured, the protease solution was placed in a constant temperature bath at 40 ° C. and left for one month, and the protease activity of the solution after standing was measured. Also, for one month, the lens having the artificial protein stain adhered to the protease solution left at 40 ° C. was immersed at 25 ° C. for 2 hours, and the stain removal rate was measured. As a result, the protease activity retention rate was 95%: the stain removal rate was 97%,
The pH was 7.0 and the contact angle of the lens was 75 °.

Example 2 1.8 g of boric acid and 0.5 g of sodium borate were dissolved in 95 ml of purified water to prepare a borate buffer having a pH of 7.2, and 0.01 g of potassium sorbitanate and 0.01 g of sodium ethylenediaminetetraacetate were dissolved. 1.0 g protease was added and dissolved.
After adding and dissolving 10 g of chlorotrimethylammonium-2-hydroxypropyldextran having a nitrogen atom content of 1.6% by weight such as quaternary ammonium, 0.01 g of polyoxyethylene glycol-alkylphenyl ether as a nonionic surfactant is added. Dissolved. Immediately after measuring the protease activity of this solution, it was left under the same conditions as in Example 1. After standing, measure the protease activity of the solution,
The stain removal rate, the pH of the solution, and the contact angle of the lens surface were measured. As a result, the protease activity retention rate was 93
%, The stain removal rate was 92%, the contact angle was 80 °, and the pH of the solution was 7.0.

Example 3 After dissolving 0.2 g of bacterial protease in 98 ml of the same borate buffer as in Example 2, chlorotriethylammonium-2-hydroxypropyl-polyvinyl alcohol having a quaternary ammonium group nitrogen atom content of 2.0% by weight was dissolved. 2.0
g and 0.2 g of a nonionic surfactant polyoxyethylene glycol cetyl ether were added and dissolved. This solution was left for one month in the same manner as in Example 1 to measure each item.
As a result, the protease activity retention rate was 90% and the stain removal rate was 85.
%, The contact angle was 76 °, and the pH of the solution was 7.0.

Comparative Example 1 In place of chlorotrimethylammonium-2-hydroxypropyl-hydroxyethylcellulose of Example 1, 0.5 g of cetyldiethylbenzylammonium chloride as an ammonium salt was added, and the same test as in Example 1 was performed. As a result, the protease activity retention rate was 68%,
The stain removal rate was 60%, the contact angle was 98 °, and the pH of the solution was 7.0.

Comparative Example 2 A test similar to that of Example 1 was performed without using the chlorotrimethylammonium-2-hydroxypropyl-hydroxyethylcellulose of Example 1. As a result, the protease activity retention rate was 80%, the stain removal rate was 70%, and the contact angle was 95%.
゜, pH of the solution was 7.0.

Table 1 summarizes the test results of the above Examples and Comparative Examples.

Effect of the Invention In the preservation solution of the present invention, dirt on the contact lens can be efficiently removed and the hydrophilicity of the surface of the contact lens can be increased simply by immersing the contact lens therein. Further, the preservation solution of the present invention has an advantage that it can be used with very good operability since the protease activity is stably maintained in a liquid state.

Claims (5)

(57) [Claims] Claims: 1. A water-soluble polymer containing a protease derived from a microorganism and a quaternary ammonium group and a hydroxyl group, wherein the water-soluble polymer is a water-soluble polymer having a hydroxyl group and glycidyl triglyceride. A preservative solution for hard contact lenses, which is a reaction product with an alkyl ammonium halide. 2. The preservation solution for hard contact lenses according to claim 1, wherein the solution contains 0.1 to 2.0% by weight of the water-soluble polymer. 3. The hard contact lens preservation solution according to claim 1, wherein the water-soluble polymer contains a nitrogen atom of a quaternary ammonium group at a ratio of 0.1 to 3.0% by weight. 4. The method according to claim 1, wherein the microorganism-containing protease is contained in an amount of 0.001 to 10% by weight.
The hard contact lens preservation solution according to the above item. 5. The composition according to claim 1, which contains at least one component selected from the group consisting of a tonicity agent, a buffer, a preservative, a surfactant, and a chelating agent, and is adjusted to pH 6.4 to 7.4. 5. The preservative solution for hard contact lenses according to any one of items 1 to 4.