JPH0836150A - Enzyme detergent for contact lens - Google Patents

Abstract

PURPOSE:To provide an enzyme detergent for a contact lens which is less stimulus for eyes and stable in a liquid state, can maintain its activity for a long time and shows an excellent cleaning effect. CONSTITUTION:This detergent liquid contains a protease produced from microorganisms and at least one kind of compd. selected from aminosulfonic acid derivs. Especially, a combination of an aminosulfonic acid deriv. and an ascorbic acid deriv. is effective.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a contact lens cleaning solution containing a microbial-derived protease.

[0002]

BACKGROUND OF THE INVENTION Proteins, lipids, and inorganic compounds derived from tears adhere to the surface of contact lenses, causing stains, which may hinder the lens, damage the cornea, cause red blood cells, etc., and stop wearing them. May have to be. Therefore, the removal of dirt is important and indispensable from the viewpoint of safety of contact lenses.

The contact lenses include water-free hard contact lenses copolymerized with methacrylic acid esters (hereinafter referred to as hard lenses) and hydrous soft contact lenses containing polyhydroxyethyl methacrylate as a main component (hereinafter referred to as "hard lens"). There is a soft lens).
Since the types of stains that adhere and the state of adhesion differ, these require cleaning methods and cleaning liquids suitable for each. In addition, with the development of new contact lens materials, it is often seen that dirt that cannot be removed by a surfactant alone adheres to the lens surface.

For this reason, there has been proposed a cleaning liquid of a type in which fine particles having a polishing action are dispersed in a cleaning liquid and the lens is rubbed to mechanically remove dirt. However, the polishing agent may change the lens surface, and the operation for cleaning is also complicated. Therefore, a cleaning solution containing an enzyme has been proposed as a highly versatile cleaning solution.

In general, when the enzyme is liquefied, the activity of the enzyme is rapidly decreased. Therefore, this type of detergent has been conventionally used as a powder or a tablet. However, various cleaning agents containing a proteolytic enzyme in liquid form have been investigated.
JP-A-60-196722, JP-A-3-2481
No. 20, JP-A-3-149517, JP-A-4
No. 510510 and Japanese Patent Application Laid-Open No. 4-161920, it is essential that they all contain a surfactant, and it is said that a sufficient cleaning effect cannot be obtained only by the action of the enzyme. Is.

Even if the cleaning liquid for a hard lens contains a large amount of surfactant, it is unlikely that the surfactant will remain on the lens. However, even with hard lenses, it has been reported that benzalkonium chloride, which is a type of ionic surfactant, is incorporated into the lenses. On the other hand, in a water-containing soft lens, the possibility of the surfactant being taken into the lens is much larger than that in a hard lens because it is water-containing, and it is strong on the eyes during wearing, especially with an ionic surfactant. May cause irritation.

[0007]

DISCLOSURE OF THE INVENTION The present invention relates to an enzyme cleaning solution for contact lenses, which does not contain a surfactant or exhibits little irritation to the eyes even when it is contained, and exhibits a high cleaning effect, particularly, a water-containing solution. For dirt such as proteins attached to both soft lenses and hard lenses of
An object of the present invention is to provide a contact lens cleaning solution containing a microbial-derived protease that can be removed without heating.

[0008]

In the present invention, the above object was achieved by incorporating at least one compound selected from aminosulfonic acid derivatives into a solution containing a microorganism-derived protease. The cleaning liquid of the present invention is particularly effective as a cleaning liquid for water-containing soft lenses and oxygen-permeable hard lenses.

Typical examples of the microorganism-derived protease used in the present invention include those obtained from Bacillus and Streptomyces bacteria, Aspergillus filamentous fungi and the like, but commercially available proteases may also be used. For example, biosease from Nagase Seikagaku,
Sabinase and Esperase manufactured by Novo Industry,
Optimase GL manufactured by Kyowa Solzyme can be used. In addition, these are rarely obtained in pure form,
It often contains amylase and / or a small amount of lipase, which may enhance the cleaning effect.

[0010] In the present invention, a neutral buffer of about pH6.5~7.5 proteases such microorganisms derived, for example, boric acid - borax, sodium or potassium citrate, sodium carbonate, Na ₂ HPO ₄ - 0.00 of KH ₂ PO ₄ etc.
It is preferably used by dissolving it in a 1 to 10% by weight solution, preferably a 0.01 to 5% by weight solution.

Next, the aminosulfonic acid derivative serves to keep the protease activity of the protease solution stable and to enhance the cleaning effect of the cleaning solution. For example, aminoethanesulfonic acid and N-methyl-2-aminoethanesulfonic acid. , N-tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid, N-tris (hydroxymethyl)
Methyl-3-aminopropanesulfonic acid, N, N-bis- (2-hydroxyethyl) -2-aminoethanesulfonic acid, N-tetradecyl-N- (2-hydroxyethyl) -2-aminoethanesulfonic acid, N -(Naphthyl)
2-Aminoethanesulfonic acid, N- (2-acetamide) -2-aminoethanesulfonic acid, 2- (morpholino) ethanesulfonic acid, 3- (N-morpholino) -2-
Hydroxypropanesulfonic acid, 2-cyclohexylaminoethanesulfonic acid, 3-cyclohexylaminoethanesulfonic acid, N-2-hydroxyethylpiperazine-
One or more compounds selected from the group consisting of aminosulfonic acids such as N′-2-ethanesulfonic acid and salts thereof are used. These compounds are preferably contained in the cleaning solution in an amount of 0.1 to 5.0% by weight, particularly 0.5 to 1.0% by weight.

Furthermore, the cleaning solution of the present invention may contain at least one compound selected from ascorbic acid derivatives, and in this case, the synergistic effect of the aminosulfonic acid derivative and the ascorbic acid derivative causes the contact lens to be very dirty. Will be removed. Examples of the ascorbic acid derivative include ascorbic acid, ascorbic acid salts,
Ascorbic acid sulfuric acid ester salt or the like can be used, and these compounds also contain 0.5 to 5.0% by weight, especially 1.0 to 1.0% by weight in the cleaning liquid.
It is preferable to contain 2.0% by weight. If the content is too large, the solubility of the solution is lowered, and the solution tends to be colored, whereas if it is too small, the effect of removing stains is reduced.

In the cleaning liquid of the present invention, if necessary, a preservative such as sorbate, 1,5-pentanediol,
Alkyltriethanolamine or the like can be added in an amount of 0.001 to 0.1% by weight. Further, in order to weaken the action of metal ions contained in protein dirt, for example, calcium ions, a chelating agent may be contained, and as the chelating agent, tetrasodium salt and disodium salt of ethylenediaminetetraacetic acid, sodium polyphosphate, etc. 0.01-3.0% by weight
It is preferable to use it in a ratio of.

Further, the product of the present invention, if necessary,
A small amount of nonionic surfactant such as polyoxyethylene sorbitol fatty acid ester, polyoxyethylene phytosterol, and polyoxyethylene phytostanal may be added. Further, in order to prepare the washing solution into a stable aqueous solution, a polyhydroxy compound such as glycerin which is a water-soluble organic solvent may be used, and the content thereof in the washing solution is about 5 to 50% by weight. preferable.

The cleaning solution of the present invention as described above is
The droplets can be used by appropriately diluting the drops with about 2 ml of isotonic saline solution, buffer solution, specific contact lens preservative solution, and soaking the lens therein.

[0016]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples. The measured values shown in Examples are obtained by the following method. Cleaning effect of hard lens An artificial soil consisting of albumin, lysozyme, globulin, and beef tallow was adhered to the surface of a contact lens material containing siloxane-methacrylate as a main component at 60 ° C., and then stained with erythrosine. After immersing the material with artificial dirt in the prescribed cleaning solution, remove the cleaning solution remaining on the surface,
Erythrosin staining was performed and the absorbance at 545 nm was measured.
The cleaning effect was calculated by the following formula. Cleaning effect = (1-absorbance after immersion / absorbance before immersion) ×
100 Soft lens cleaning effect A polyhydroxyethylmethacrylate test piece with a water content of 38.5% (20 mm x 40 mm x 0.5 mm) is coated with artificial stains consisting of albumin, lysozyme, globulin, and beef tallow.
It was attached to the lens surface at 0 ° C. After immersing the test piece with artificial stains in a predetermined cleaning solution, the cleaning solution remaining on the surface was removed and the absorbance at 280 nm was measured. The cleaning effect was calculated by the following formula. Cleaning effect = (1-absorbance after immersion / absorbance before immersion) ×
Enzyme activity of 100 protease The protease activity was measured according to a known method using casein digestion (see page 291 of Journal of General Phyalology 30 (1947)).

Example 1 100 g of boric acid-borax buffer was added to a protease derived from a bacterium,
Bioprase NY 7.0 g, 2-aminoethanesulfonic acid 1 g, sodium ascorbate 1.0 g, glycerin 5
0 g, tetrasodium salt of ethylenediaminetetraacetic acid 0.1 g
Was dissolved, and undissolved substances of contaminants were removed by filtration to obtain a cleaning solution for contact lenses. The protease activity of this solution was 6500 units. Moreover, when a part of this solution was heated at 40 ° C. for 2 weeks and the protease activity was measured, the activity retention was 95%, which was 6200 units.
A test piece of a hard lens material with artificial stain and a water-containing soft lens test piece was immersed in a solution obtained by diluting 0.5 g of this washing solution with 10 g of physiological saline, and allowed to stand at 20 ° C. for 2 hours, before and after immersion of the test piece. The cleaning effect was evaluated from the change in the absorbance. A cleaning effect of 98% was recognized for both the hard lens and the hydrous soft lens.

Example 2 In 100 g of a phosphate buffer solution, a protease derived from a bacterium, 5.0 g of bioprase NY, 0.5 g of N-methyltaurine, 1.5 g of ascorbic acid, 40 g of glycerin, and 0.1 g of tetrasodium salt of ethylenediaminetetraacetic acid were dissolved. Then, undissolved substances of contaminants were removed by filtration to obtain a contact lens cleaning liquid.
The protease activity of this solution was 4800 units. Moreover, when a part of this liquid was heated at 40 ° C. for 2 weeks and then the protease activity was measured, the activity retention rate was 4350 units, and the activity retention rate was 91%. Dip a hard lens material with artificial dirt and a test piece of hydrous soft lens into a solution obtained by diluting 0.5 g of this cleaning solution with 10 g of physiological saline, and
The test piece was allowed to stand for 2 hours at 0 ° C., and the cleaning effect was evaluated from the change in absorbance before and after immersion of the test piece. The hard lens showed a cleaning effect of 97% and the hydrous soft lens showed a cleaning effect of 95%.

EXAMPLE 3 100 g of boric acid-borax buffer was added to a protease derived from a bacterium,
Optimase GL 5.0 g, N-tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid 0.1 g, ascorbic acid sulfate disodium 1.5 g, glycerin 30 g, sodium polyphosphate 0.1 g, polyoxyethylene phytosterol 0.1 g. 01 g was dissolved, and undissolved substances of contaminants were removed by filtration to obtain a contact lens cleaning liquid.
The protease activity of this solution was 5400 units. Moreover, when a part of this solution was heated at 40 ° C. for 2 weeks and the protease activity was measured, the activity retention was 89% in 4,800 units. 0.5 g of this cleaning solution was diluted with 10 g of a lens storage solution containing a phosphate buffer, and a hard lens material with artificial dirt attached and a test piece of a water-containing soft lens were immersed in the solution and allowed to stand at 20 ° C. for 2 hours. The cleaning effect was evaluated from the change in absorbance before and after the test piece was immersed. A cleaning effect of 96% was recognized for both the hard lens and the hydrous soft lens.

Example 4 In 100 g of a phosphate buffer, a protease derived from a bacterium, 5.0 g of bioprase NY, 1.0 g of N-tris (hydroxymethyl) methyl-3-aminopropanesulfonic acid, 2.0 g of disodium ascorbate sulfate, Glycerin 40
g and 0.1 g of tetrasodium ethylenediaminetetraacetate were dissolved, and undissolved substances of contaminants were removed by filtration to obtain a cleaning solution for contact lenses. The protease activity of this solution is 485
It was 0 unit. After heating a part of this solution at 40 ° C. for 2 weeks, the protease activity was measured.
At 00 units, the activity retention was 93%. A test piece of a hard lens material with artificial stain and a water-containing soft lens test piece was immersed in a solution obtained by diluting 0.5 g of this washing solution with 10 g of physiological saline, and allowed to stand at 20 ° C. for 2 hours, before and after immersion of the test piece. The cleaning effect was evaluated from the change in the absorbance. The hard lens exhibited a cleaning effect of 98%, and the water-containing soft lens exhibited a cleaning effect of 98%.

Example 5 In 100 g of phosphate buffer solution, bacterial protease, biopulase NY 5.0 g, N- (2-acetamido) -2-aminoethanesulfonic acid 1.0 g, ascorbic acid sulfate disodium 1.0 g, glycerin 30 g of ethylenediaminetetraacetic acid tetrasodium and 0.1 g were dissolved, and undissolved substances of contaminants were removed by filtration to obtain a cleaning solution for contact lenses. The protease activity of this solution was 4900 units. Moreover, after heating a part of this liquid at 40 ° C. for 2 weeks,
When the protease activity was measured, in 4500 units,
The retention of activity was 92%. A test piece of a hard lens material with artificial stain and a water-containing soft lens test piece was immersed in a solution obtained by diluting 0.5 g of this washing solution with 10 g of physiological saline, and allowed to stand at 20 ° C. for 2 hours, before and after immersion of the test piece. The cleaning effect was evaluated from the change in the absorbance. Hard lens is 95
%, The water-containing soft lens showed a cleaning effect of 96%.

Example 6 In 100 g of a phosphate buffer solution, a bacteria-derived protease, Optimase GL 5.0 g, N- (2-acetamido) -2-aminoethanesulfonic acid 1.5 g, ascorbic acid sulfate disodium 0.5 g, Glycerin 30g, sodium polyphosphate 0.1g, polyoxyethylene phytosterol 0.1g.
01 g was dissolved, and undissolved substances of contaminants were removed by filtration to obtain a contact lens cleaning liquid. The protease activity of this solution was 5300 units. In addition, a part of this liquid
After heating at 0 ° C. for 2 weeks, the protease activity was measured and found to be 4800 units, and the activity retention rate was 91%. A test piece of a hard lens material with artificial stain and a water-containing soft lens test piece was immersed in a solution obtained by diluting 0.5 g of this washing solution with 10 g of physiological saline, and allowed to stand at 20 ° C. for 2 hours, before and after immersion of the test piece. The cleaning effect was evaluated from the change in the absorbance. Hard lenses are 94%, hydrous soft lenses are 93%
Showed the cleaning effect.

Example 7 In 100 g of Tris-hydrochloric acid buffer solution, a protease derived from a bacterium, 7.0 g of bioprase NY and 2.0 aminoaminosulfonic acid 2.0
g, sodium ascorbate 0.2 g, glycerin 30
g and 0.1 g of tetrasodium ethylenediaminetetraacetate were dissolved, and undissolved substances of contaminants were removed by filtration to obtain a cleaning solution for contact lenses. The protease activity of this solution is 645
It was 0 unit. Moreover, after heating a part of this solution at 40 ° C. for 2 weeks, the protease activity was measured to be 58
At 00 units, the activity retention was 90%. A test piece of a hard lens material with artificial stain and a water-containing soft lens test piece was immersed in a solution obtained by diluting 0.5 g of this washing solution with 10 g of physiological saline, and allowed to stand at 20 ° C. for 2 hours, before and after immersion of the test piece. The cleaning effect was evaluated from the change in the absorbance. The hard lens showed a cleaning effect of 90%, and the hydrous soft lens showed a cleaning effect of 93%.

Example 8 In 100 g of Tris-hydrochloric acid buffer solution, a protease derived from a bacterium, 7.0 g of bioprase NY, and 2-aminoethanesulfonic acid 2.
5g, glycerin 30g, potassium sorbate 0.01
g and 0.5 g of sodium polyphosphate were dissolved, and undissolved substances of contaminants were removed by filtration to obtain a contact lens cleaning liquid.
The protease activity of this solution was 6300 units. Moreover, when a part of this solution was heated at 40 ° C. for 2 weeks and the protease activity was measured, the activity retention was 85% in 5350 units. 0.5g of this cleaning solution was diluted with 10g of physiological saline solution, and the hard lens material with artificial dirt adhered to it and the test piece of hydrous soft lens were dipped into
The test piece was left standing at 0 ° C. for 2 hours, and the cleaning effect was evaluated from the change in absorbance before and after the test piece was immersed. The cleaning effect was 82% for the hard lens and 90% for the hydrous soft lens.

Example 9 In 100 g of phosphate buffer solution, bacterial protease, bioprase NY 5.0 g, N-tris (hydroxymethyl) methyl-3-aminopropanesulfonic acid 2.5 g, glycerin 30 g, sodium polyphosphate 0.5 g Was dissolved, and undissolved substances of contaminants were removed by filtration to obtain a cleaning solution for contact lenses. The protease activity of this solution was 4700 units. Moreover, after heating a part of this liquid at 40 ° C. for 2 weeks,
When the protease activity was measured, it was 3950 units.
The activity retention was 85%. The hard lens material with artificial dirt and the test piece of the water-containing soft lens were immersed in a solution obtained by diluting 0.5 g of this cleaning solution with 10 g of the lens preservation solution, and allowed to stand at 20 ° C. for 2 hours to dip the test piece. The cleaning effect was evaluated from the change in absorbance before and after. Hard lens is 80
%, The water-containing soft lens showed a cleaning effect of 88%.

Comparative Example 1 In 100 g of boric acid-borax buffer solution, a protease derived from a bacterium, 7.0 g of bioprase NY, 40 g of glycerin and 0.1 g of sodium polyphosphate were dissolved, and undissolved matters of contaminants were removed by filtration. A contact lens cleaning solution was obtained. The protease activity of this solution was 6800 units. Moreover, when a part of this solution was heated at 40 ° C. for 2 weeks and then the protease activity was measured, the activity retention rate was 4100 units, and the activity retention rate was 60%. 0.5 g of this washing solution is 10 g of physiological saline.
The test pieces of the hard lens material and the water-containing soft lens to which artificial stains were attached were immersed in the liquid diluted with, and allowed to stand at 20 ° C. for 2 hours, and the cleaning effect was evaluated from the change in the absorbance before and after the immersion of the test pieces. . The hard lens showed a cleaning effect of 71% and the hydrous soft lens showed a cleaning effect of 60%.

Comparative Example 2 In 100 g of a boric acid-borax buffer solution, a bacterial protease, bioprase NY 5.0 g, glycerin 30 g, polyoxyethylene phytosterol 0.001 g, and ethylenediaminetetraacetic acid tetrasodium 0.1 g were dissolved to give a mixed solution. Undissolved substances were removed by filtration to obtain a contact lens cleaning liquid. The protease activity of this solution was 4900 units. Moreover, after heating a part of this liquid at 40 ° C. for 2 weeks,
When the protease activity was measured, in 2500 units,
The retention rate of activity was 51%. A test piece of a hard lens material with artificial stain and a water-containing soft lens test piece was immersed in a solution obtained by diluting 0.5 g of this washing solution with 10 g of physiological saline, and allowed to stand at 20 ° C. for 2 hours, before and after immersion of the test piece. The cleaning effect was evaluated from the change in the absorbance. Hard lens is 55
%, The water-containing soft lens showed a cleaning effect of 58%.

Comparative Example 3 In 100 g of boric acid-borax buffer solution, a protease derived from a bacterium, 5.0 g of bioprase NY, 0.5 g of sodium ascorbate, 40 g of glycerin, 0.01 g of polyoxyethylene phytosterol, 0.01 g of tetrasodium ethylenediaminetetraacetate were added. 1 g was dissolved, and undissolved substances of contaminants were removed by filtration to obtain a contact lens cleaning liquid. The protease activity of this solution was 4800 units. Moreover, when a part of this solution was heated at 40 ° C. for 2 weeks and the protease activity was measured, the activity retention rate was 54% at 2600 units.
Met. 0.5 g of this cleaning solution was diluted with 10 g of a lens preservation solution containing a phosphate buffer, and a hard lens material with artificial dirt and a test piece of a water-containing soft lens were immersed in the solution and allowed to stand at 20 ° C. for 2 hours. After that, the cleaning effect was evaluated from the change in the absorbance before and after the immersion of the test piece. 6 hard lenses
The cleaning effect of 0% and the water-containing soft lens was 62%.

The results obtained in the above Examples and Comparative Examples are shown in Table 1. From this table, it can be seen that the cleaning solution of the present invention is in a liquid state, the protease activity is stably maintained, and the stains on the contact lens are efficiently removed even if the surfactant is not contained.

[0030]

[Table 1]

[0031]

EFFECT OF THE INVENTION The cleaning solution of the present invention is stable in a liquid state and retains protease activity, and can be a product having an extremely excellent cleaning effect without using a stimulating surfactant. Stable and safe to use. Further, it exhibits an excellent cleaning effect on both hard lenses and soft lenses.

Claims (6)

[Claims] 1. An enzyme cleaning solution for contact lenses, which contains a microorganism-derived protease together with at least one compound selected from aminosulfonic acid derivatives. 2. The cleaning solution according to claim 1, which contains a microbial-derived protease together with at least one compound selected from aminosulfonic acid derivatives and at least one compound selected from ascorbic acid derivatives. 3. The cleaning liquid according to claim 1, which contains the aminosulfonic acid derivative in an amount of 0.1 to 5% by weight. 4. An ascorbic acid derivative in an amount of 0.1 to 5% by weight.
The cleaning liquid according to claim 2, which contains the cleaning liquid. 5. A polyhydroxy compound is contained in an amount of 5 to 50% by weight.
The cleaning liquid according to claim 1, which contains the cleaning liquid. 6. The cleaning liquid according to claim 1, which contains at least one agent selected from the group consisting of isotonic agents, buffers, preservatives, surfactants and chelating agents.