JP2002020320A - Antiseptic agent for eye drop - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antiseptic agent for eye drop having the excellent a effect and safe to human body. SOLUTION: A polymer of a basic amino acid such as polylysine, polyornithine, polyarginine and polyhistidine is useful as an antiseptic agent for eye drop having excellent antiseptic effect. The antiseptic effect of eye drop can be further promoted by using the polymer of basic amino acid in combination with boric acid and/or borax.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a preservative for eye drops and an eye drop.

[0002]

2. Description of the Related Art Eye drops are administered directly to the sensitive organs of the human body, which is the eye. Preservatives used in eye drops cannot be treated in the same manner as preservatives (preservatives) used in foods, drinks, contact lens preservatives, etc., for example, eye irritation, various side effects that may occur, Furthermore, in order to enable long-term storage, the temporal stability of the ophthalmic solution must be considered.

Conventionally, benzalkonium chloride, benzethonium chloride, sorbic acid and the like have been used as preservatives for eye drops.

[0004] However, benzalkonium chloride and benzethonium chloride have a high preservative effect, but may cause corneal damage if the concentration thereof is high, so that there is a certain restriction on the use concentration. In addition, these preservatives may cause a mixing change (chemical reaction) with an acidic additive, and have a property of being easily adsorbed to a filter or an ophthalmic container. On the other hand, sorbic acid has low adsorption to eye drops, but does not have a remarkable preservative effect.In addition, depending on pH, stability may be reduced and eye irritation may occur. Additives have certain restrictions.

[0005]

Therefore, an ophthalmic preservative for an ophthalmic solution which has an excellent preservative effect, is hardly restricted by drugs and other additives which can be incorporated at the same time, and is also excellent in safety. Agents are needed.

[0006]

Means for Solving the Problems The present inventors have searched for an ophthalmic solution preservative which can solve the above problems, and found that a polymer of a basic amino acid exhibits an excellent antiseptic effect in ophthalmic solution, It has been found that the preservative effect of the ophthalmic solution can be further enhanced by using a polymer of a sex amino acid and boric acid and / or borax in combination, and has reached the present invention.

That is, the present invention relates to a preservative for eye drops and an eye drop comprising a polymer of a basic amino acid and having an excellent preservative effect. Further, the present invention relates to a preservative for eye drops and an eye drop comprising a polymer of a basic amino acid and boric acid and / or borax, which have excellent preservative effects.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The preservative for eye drops of the present invention comprises a polymer of a basic amino acid. Examples of the polymer of a basic amino acid include polylysine, polyornithine, polyarginine, polyhistidine, and the like. Any of these may be used alone, or two or more may be used in combination. . Polymers of these basic amino acids are not absorbed by the ocular tissues after instillation and are easily decomposed into amino acids, which are components in the living body, by proteolytic enzymes in the living body. The amount of the basic amino acid polymer to be added is not particularly limited, but is in the range of 0.00001 to 5.0% by weight, and more preferably in the range of 0.0001 to 3.0% by weight. If the amount of the basic amino acid polymer added to the ophthalmic solution is less than 0.00001% by weight, a sufficient antiseptic effect cannot be obtained in the ophthalmic solution, and if it exceeds 5.0% by weight, the antiseptic effect is hardly improved. Because.

The weight average molecular weight of the polymer of the basic amino acid is not particularly limited, but is in the range of 500 to 500,000, more preferably 3000 to 200,000. If the weight average molecular weight is less than 500, a sufficient preservative effect cannot be obtained in the ophthalmic solution, and if it exceeds 500,000, the ophthalmic solution becomes too viscous and may have an unpleasant sticky feeling.

The preservative for ophthalmic solution of the present invention comprises boric acid and / or boric acid.
Alternatively, if borax is added, the preservative effect of the ophthalmic solution is further enhanced. The amount of boric acid and / or borax added in the ophthalmic solution is not particularly limited, but is 0.001 to 5.0.
% By weight, more preferably from 0.01 to 2.0% by weight. In consideration of eye safety, it is desirable that the amount of boric acid and / or borax not exceed 5.0% by weight.

The ophthalmic solution containing the preservative for ophthalmic solution of the present invention contains, as an additive, other than the above-mentioned preservative, of course, a drug as an active ingredient, as an isotonic agent, a buffer, a pH adjuster, A solubilizer, a thickener, a stabilizer, a preservative, and the like can be appropriately blended. The polymer of a basic amino acid has little interaction with other compounding components (drugs, additives, and the like), and there is little restriction on drugs, other additives, and the like to be compounded at the same time.

Accordingly, the drug to be combined with the preservative for ophthalmic solution of the present invention is not particularly limited. For example, anti-glaucoma (timolol, prostaglandin derivative, carbonic anhydrase inhibitor, etc.), various vitamins (vitamin B2, vitamin B6, vitamin B12, vitamin E, panthenol, etc., decongestants (tetrahydrozoline hydrochloride, naphazoline hydrochloride, etc.), anti-inflammatory agents (diclofenac, indomethacin, fluorometholone, planoprofen, dipotassium glycyrrhizinate, ε- Aminocaproic acid, etc.), antihistamines (chlorpheniramine maleate, diphenhydramine hydrochloride, etc.), antiallergic agents (sodium cromoglycate, etc.), antibacterial agents (quinolone antibacterial agents, cephalosporins, sodium sulfacetamide, sulfamethoki) Sazol), amino acids Potassium L- aspartic acid,
Aminoethylsulfonic acid, sodium chondroitin sulfate, etc.), diagnostic reagents (sodium fluorescein, etc.),
Examples include sodium hyaluronate and neostigmine methyl sulfate.

Examples of the tonicity agent include glycerin, propylene glycol, sodium chloride, potassium chloride,
Sorbitol, mannitol and the like can be mentioned.

Examples of the buffer include phosphoric acid, phosphate, citric acid, acetic acid, ε-aminocaproic acid, tromethamol and the like.

Examples of the pH adjuster include hydrochloric acid, citric acid, phosphoric acid, acetic acid, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like.

As a solubilizer to be added when a drug or other additives are hardly soluble in water, for example, polysorbate 8
0, polyoxyethylene hydrogenated castor oil 60, Macrogol 4000 and the like.

Examples of the thickener include cellulosic polymers such as hydroxypropylmethylcellulose and hydroxypropylcellulose, polyvinyl alcohol and polyvinylpyrrolidone, and examples of the stabilizer include edetic acid and sodium edetate. be able to.

Examples of preservatives (preservatives) other than the preservatives for ophthalmic solutions of the present invention include general-purpose sorbic acid, potassium sorbate, benzalkonium chloride, benzethonium chloride, methyl parahydroxybenzoate, propyl paraoxybenzoate,
Chlorobutanol and the like can be mentioned, and the preservative for eye drops of the present invention can be used in combination with these preservatives. When these preservatives are used in combination, the amount of general-purpose preservatives can be significantly reduced, and the safety for the human body is further improved.

The pH of the ophthalmic solution containing the preservative for ophthalmic solution of the present invention is preferably set to 4.0 to 8.0.
The osmotic pressure ratio is desirably set to around 1.0.

Since the ophthalmic solution containing the preservative for ophthalmic solution of the present invention contains a polymer of a basic amino acid such as polylysine, polyornithine, polyarginine, polyhistidine, it can be used for various bacteria such as bacteria and fungi. On the other hand, it has a remarkable antibacterial effect, is excellent in stability, is extremely safe for the human body, and has little eye irritation and is excellent in comfort.

Hereinafter, the present invention will be described in detail with reference to examples, but these do not limit the scope of the present invention.

[0022]

EXAMPLES In order to examine the preservative effect of the ophthalmic solution containing the preservative for ophthalmic solution of the present invention, the following preservative efficacy test was carried out.

1. Preservation efficacy test for E. coli Ophthalmic solutions having the components shown in Examples 1 to 12 in Table 1 were prepared by a conventional method. Further, to each ophthalmic solution, sodium chloride was added as an isotonic agent, the osmotic pressure was adjusted to 1.0, and sodium dihydrogen phosphate was further added as a buffering agent. In addition, the pH was adjusted to 6.0 (in the boric acid added group, boric acid itself has a buffering action, so no buffer was added). The preservative efficacy test was performed in accordance with the preservative efficacy test method of the 13th revised Japanese Pharmacopoeia. Using Escharichia Coli (E. coli) as a test bacterium, the number of viable bacteria after 6 hours and 14 days was measured, and the survival rate of the bacterium was calculated according to the following formula. Table 1 shows the test results.

Survival rate (%) = viable cell count after 6 hours or 14 days / initial cell count × 100

[0025]

[Table 1] 2. A. Niger Preservation Efficacy Test Ophthalmic solutions of the components shown in Examples 13 to 18 in Table 2 were prepared by a conventional method. Further, sodium chloride was added to each ophthalmic solution as an isotonic agent, the osmotic pressure was adjusted to 1.0, and if necessary, sodium hydroxide was added to adjust the pH to 6.0. The preservative efficacy test was performed in accordance with the preservative efficacy test method of the 13th revised Japanese Pharmacopoeia. The number of viable cells after 7 days was measured using Aspergillus niger (A. niger) as a test bacterium, and the survival rate of the bacterium was calculated according to the following formula. Table 2 shows the test results.

Survival rate (%) = viable cell count after 7 days / initial cell count × 100

[0027]

[Table 2]

[0028]

As is evident from the results in Table 1, all of polylysine, polyornithine and polyarginine exhibit an excellent preservative effect against bacteria Escharichia Coli. In addition, when a polymer of these basic amino acids and boric acid are used in combination, the preservative effect is significantly increased. As is clear from the results in Table 2, when polylysine, polyornithine or polyarginine is used in combination with boric acid, an excellent antiseptic effect is exerted on the fungus Aspergillus niger. As described above, since the ophthalmic solution containing the preservative for ophthalmic solution of the present invention contains a polymer of a basic amino acid as a component thereof, it exhibits a remarkable antibacterial action against various bacteria such as bacteria and fungi. .

Claims (7)

[Claims] An antiseptic for ophthalmic solution comprising a polymer of a basic amino acid. 2. An ophthalmic preservative comprising a polymer of a basic amino acid and boric acid and / or borax. 3. The polymer of a basic amino acid is polylysine,
3. The preservative for ophthalmic solution according to claim 1, wherein the preservative comprises at least one selected from the group consisting of polyornithine, polyarginine and polyhistidine. 4. An ophthalmic solution containing the preservative for ophthalmic solution according to claim 1. 5. An ophthalmic preservative obtained by blending a polymer of a basic amino acid. 6. An ophthalmic preservative obtained by blending a polymer of a basic amino acid with boric acid and / or borax. 7. An ophthalmic solution containing the preservative for ophthalmic solution according to claim 5 or 6.