JPS5989617A - Eye drop - Google Patents

Abstract

PURPOSE:An eye drop showing highly antiseptic effect with a small amount of it without damaging functions of eye drop and causing clouding, obtained by blending an eye drop containing a sulfamide and an organic amine with a quaternary ammonium salt and a hydrophilic nonionic surface active agent. CONSTITUTION:An eye drop containing a sulfamide and an organic amine is blended with a soluble amount of a quaternary ammonium salt, preferably 0.002-0.02wt%, especially 0.005-0.015wt% benzalkonium chloride, or benzethonium chloride based on the total amount and 0.05-0.5wt%, especially 0.05- 0.2wt% hydrophilic nonionic surface active agent such as polyoxyethylene sorbitan monooleate, etc. The eye drop containing the sulfamide and the organic amine has preferably 7.5-9.0pH. The amount of the sulfamide blended is 3-5% (weight/volume %) based on the total amount of the eye drop, and the amount of the organic amine blended is preferably an amount to give a molar ratio of the sulfamide to the organic amine of (1:0.9)-(1:1.2).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an ophthalmic solution containing a sulfa drug such as sulfamethoxazole, and more specifically to an ophthalmic solution containing a sulfa drug with excellent preservative power.

Conventionally, it is known that sulfa drugs such as sulfamethoxazole are added to eye drops).Also, in order to impart preservative power to this divine sulfa drug-containing eye drop, alkyl esters of rose hydroxybenzoic acid such as butyl rose hydroxybenzoate are added. It is also known to add. However, the preservative power of the sulfa drug-containing eye drops containing rose hydroxybenzoic acid alkyl ester was not high and was extremely insufficient. In this case, increasing the amount of rose hydroxybenzoic acid alkyl ester added has problems in terms of solubility, eye irritation, etc., and quaternary compounds such as benzalkonium chloride, which are commonly used in general eye drops, may cause problems such as solubility and eye irritation. When ammonium salts are added, they interact with sulfa drugs such as sulfamethoxazole, causing the system to become cloudy, and chlorobutanol may interact with sulfa drugs such as sulfamethoxazole, depending on the pH of the ophthalmic solution containing them. I)H
7.1) Because of this, the separation rate of chlorobutanol is so fast that it cannot be blended. For this reason, it has been desired to effectively increase the preservative power of ophthalmic solutions containing sulfa agents without impairing their functions.

In view of the above circumstances, the researchers conducted intensive research on improving the preservative power of sulfa drug-containing eye drops, and found that a sulfa drug containing an organic amine was added to the ophthalmic solution containing benzalkonium chloride. When a grade ammonium salt is used in combination with a hydrophilic nonionic surfactant such as polyoxyethylene sorbitan monooleate, white turbidity does not occur;
It was discovered that the ophthalmic solution is solubilized to give a transparent system, and that this eye drop has extremely high preservative power, leading to the present invention.

The present invention will be explained in more detail below.

The ophthalmic solution according to the present invention contains a sulfa drug, an organic amine, a quaternary ammonium salt, and a hydrophilic nonionic surfactant.

Examples of the sulfur drugs include sulfur amethoxazole, sulfisoxazole, etc., and one or more of these may be used. The amount of these sulfa drugs to be blended is not particularly limited, but is usually 3 to 5% (retention/volume %, hereinafter the same) of the entire eye drop.

Furthermore, examples of organic amines include monoethanolamine, jetanolamine, triethanolamine, etc., and one or more of these may be used. The molar ratio of sulfa drug and organic amine is i:o, 9 to 1.
: 1.2, especially preferably in an amount in the range of 1:1 to 1:i, i. By using the organic amine in the above range, it is possible to solubilize the sulfa drug and to Together with the quaternary ammonium salt and the hydrophilic nonionic surfactant, it provides excellent preservative power.

The pH of the ophthalmic solution of the present invention containing a sulfa drug and an organic amine is preferably 7.5 to 9.0; if the pH is too low, the solubility of the sulfa drug will decrease and precipitation will occur.
If H is too high, the stability as an eye drop may be impaired.

The ophthalmic solution of the present invention is a system containing a sulfa drug and an organic amine combined with a quaternary ammonium salt and a woody nonionic surfactant, thereby making it possible to obtain a transparent ophthalmic solution with remarkable preservative power. can.

Here, the quaternary ammonium salts include alkylpyridinium salts such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium ammonium chloride;
Examples include monolong (i)alkyltrishort-chain alkyl ammonium salts such as cetyltrimethylammonium chloride, and these 14'' [! Alternatively, two or more types may be used, but benzalkonium chloride and j*Nts benzethonium are preferably used for 4h. In addition, as hydrophilic nonionic surfactants, polyoxyethylene sorbitan monofatty acids such as polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, polyoxyethylene monostearate, Polyoxyethylene monolti pIJ3 (f
Type 2 hydrophilic ones include polyoxyethylene alcohol ethers such as polyoxyethylene lauryl ether, and one or more of these may be used.

Note that the number of moles of polyoxyethylene is desirably 10 moles or more from the viewpoint of feeling in use.

The blending amount of the quaternary ammonium salt is the amount dissolved in the ophthalmic solution, and varies depending on the sulfa drug, organic amine, type a of the nonionic surfactant, the blending amount, the quaternary ammonium salt, etc. , 0.002-0.02% of the total,
In particular, it is preferably 0.005 to 0.015%.

If it is less than 0.002%, sufficient jDb protection may not be obtained, and if it is more than 0.02%, there may be a problem in terms of safety. The amount of nonionic surfactant to be blended is preferably 0.05 to 0.5%, particularly 0.05 to 0.2%.

In addition to the sulfa drug, the eye drops of the present invention may further include dipotassium glycyrrhizinate, diphenhydramine hydrochloride, potassium asparagine, aminoethylsulfonic acid, 6-aminocaprone, chlorpheniramine maleate, neostigmine methyl sulfate, etc. It is also possible to blend isotonizing agents such as sodium chloride and potassium chloride, and flat molecular additives such as polyhydric alcohol, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethyl cellulose, and hydroxypropyl cellulose. .

EXAMPLES Hereinafter, the present invention will be specifically explained by showing examples and comparative examples, but the present invention is not limited to the following examples.

[Examples 1 to 2, Comparative Examples 1 to 3] Eye drops with the formulations shown in Table 1 (all percentages in the table indicate the amount/volume percentage), their appearance, and antibacterial effects against various microorganisms We investigated the preservative power based on strength.

The results are also listed in Table 1.

In addition, the appearance of the eye drops may be 0, which is normal for eye drops, or it may be cloudy (
×) is evaluated as an indicator, and the antiseptic strength testing station is the inter-plane preservative power test method (liquid medium method) [Pharmaceutical Research (Japan Official Pledge Association) Vol. 4. &2. P177 (1973))
The results were expressed in terms of microorganism death time.

The preservative power judgment is O, which indicates that the preservative power is sufficient, or not sufficient (X
) was evaluated based on the criteria.

From the results in Table 1, it was found that a system containing a sulfa drug (sulfamethoxazole) and an organic amine was combined with a quaternary ammonium salt (benzalkonium chloride) and a wood-philic nonionic surfactant (polyoxyethylene sorbitan monooleate). ), it was found that a transparent eye drop having excellent preservative power could be obtained.

[Example 3] An eye drop having the same formulation as in Example 1 was prepared, except that benzethonium chloride was used instead of benzalkonium chloride.

This eye drop was transparent, and its preservative power was sufficiently satisfactory as in Example 1.

[Example 4] An eye drop having the same formulation as in Example 1 was prepared except that polyoxyethylene monostearate (1)-40) was used instead of polysorbate 80.

This eye drop also had the same effect as Example 3.

[Example 5.6] In the formulation of Example 1, an eye drop containing 0.5% polysorbate 80 (Example 5), an eye drop containing 0.05% polysorbate 80 (Example 6)
were prepared respectively.

These eye drops also had the same effects as in Example 3.

Applicant: Lion Corporation Agent: Patent attorney Furuji Kojima

Claims (1)

[Scope of Claims] / An ophthalmic solution comprising an ophthalmic solution containing a sulfa drug and an amine, mixed with an orally dissolvable quaternary ammonium salt and a hydrophilic nonionic surfactant. 1. Eye drops for current combat.Eye drops as described in Section 1 or Section 2.