JPS5989616A - Eye drop - Google Patents

Abstract

PURPOSE:An eye drop showing highly antiseptic power with its small amount 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 para-hydroxybenzoic acid alkyl ester. CONSTITUTION:An eye drop containing a sulfamide and an organic amine is blended with a soluble amount of a quaternary ammonium salt, preferably <=6ppm, especially 3-5ppm benzalkonium chloride, or benzethonium chloride based on total amount and 0.005-0.1wt%, especially 0.01-0.05 para-hydroxybenzoic acid alkyl ester, preferably butyl ester. The eye drop containing the sulfamide and the organic amine has preferably 7.5-9.0pH. Sulfamethoxazole, etc. is used as the sulfamide, the amount of it blended is 3-5wt% based on the total amount of 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 sul7amethoxazole/L/, and more specifically, to an ophthalmic solution containing a sulfa drug with excellent preservative power.

Conventionally, it has been known to incorporate sulfa drugs such as sul-7-amethoxazole into eye drops, and in order to impart preservative power to this yuzu sulfa drug-containing eye drops, rose hydroxybenzoic acid alkyl esters such as butyl rose hydroxybenzoate have been added. It is also known to do so. 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 rosehydroxybenzoic acid alkyl ester added has problems in terms of solubility, eye irritation, etc., and quaternary ammonium such as benzalkonium chloride, which is commonly used in general eye drops, When salt is added, it interacts with sulfa drugs such as sulfamethoxazole and makes the system cloudy, and chlorobutanol has a pH of 1) H7, Since the value is as high as 5 or more, the decomposition rate of chlorobutanol is fast and it cannot be blended. Therefore, it has been desired to effectively increase the preservative power of sulfa drug-containing eye drops without impairing their functionality.

In view of the above circumstances, the present inventors conducted intensive research on improving the preservative power of ophthalmic solutions containing sulfa drugs. When an ammonium salt is added, a very small amount of about 6 ppm does not cause white turbidity, and the quaternary ammonium salt is solubilized to provide a transparent system.
Even with a slight increase in laxity, this fourth
When ammonium salts are used in combination with parahydroxyammonium esters and incense alkyl esters, quaternary ammonium salts and alkyl parahydroxybenzoates are used, even though they do not have sufficient preservative power when used alone. It was discovered that esters act synergistically to significantly increase the preservative power of a single sulfa drug-containing ophthalmic solution, leading to the present invention.

Hereinafter, the present invention will be explained in detail.

The ophthalmic solution according to the present invention contains a sulfa drug, an organic amine, a quaternary ammonium salt, and an alkyl hydroxybenzoic acid ester.

Here, sulfa drugs include sulfamethoxazole, 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% (weight/volume %, hereinafter the same) of the entire eye drop.

Examples of organic amines include monoethanolamine, jetanolamine, triethanolamine, etc., and one or more of these ITa or two or more are used. The blending amount is such that the molar ratio of sulfa drug and organic amine is 1:0.9~
The amount is preferably in the range of 1:1.2, especially 1:1 to 1:1.1, and by using Awa & Amine in the above range, it is possible to solubilize the sulfa drug. At the same time, along with the quaternary ammonium salt and paraoxybenzoic starch ester, it provides excellent preservative power.

In addition, it is preferable that the I)H of the ophthalmic solution of the present invention in which an organic amine is added to a sulfa drug is 7.5 to 9.0; if the pH is too low, the solubility of the sulfa drug decreases and precipitation occurs; If the pH is too high, the stability as an eye drop may be impaired.

The ophthalmic solution of the present invention is one in which a quaternary ammonium salt and a barahydroxybenzoic acid alkyl ester are blended into a thread containing a sulfa drug and an organic amine, which can significantly increase the preservative power of the ophthalmic solution. . On the other hand, even if a quaternary ammonium salt or a bara hydroxybenzoic acid alkyl ester is used alone, sufficient preservative power cannot be imparted, and the purpose of the present invention cannot be achieved (quaternary ammonium salt (Containing a large amount of sulfa drug instillation solution causes cloudiness, and using a large amount of rose hydroxybenzoin alkyl or ester is undesirable in terms of solubility and eye irritation.)

Here, the quaternary ammonium salts include alkylpyridinium salts such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium ammonium chloride;
Examples include mono-long-chain alkyl tri-short-chain alkyl ammonium salts such as cetyltrimethylammonium chloride, and one or more of these may be used, with benzalkonium chloride and benzethonium chloride being particularly preferred. In addition, examples of the parahydroxybenzoic acid alkyl esters include methyl ester, ethyl ester, propyl ester, butyl ester, etc., and one or more of these may be used, but butyl ester is particularly preferably used. .

The amount of quaternary ammonium salt is the amount that is soluble in the eye drops, and the amount of quaternary ammonium salt is the amount that is soluble in the ophthalmic solution.
Although it varies depending on the type of ammonium salt, 6ppm
Hereinafter, it is particularly preferable to use 3 to 51)I)m, and even if such a small amount is used in combination with rose hydroxybenzoic acid alkyl ester, a sufficiently high preservative power can be obtained. In addition, the compound needle of rose hydroxybenzoic acid alkyl ester is 0.005 to 0.1% of the total, especially 0.01 to 0.05%.
% is preferable.

The eye drops of the present invention further contain dipotassium glycyrrhizinate, diphenhydramine hydrochloride, potassium aspartate, aminoethyl sulfonic acid, ε-aminocaproic acid, chlorpheniramine maleate, neostigmine methyl sulfate, etc. in addition to the sulfa drug, as necessary. and isotonizing agents such as sodium chloride and potassium chloride, solubilizing agents such as polyhydric alcohols and nonionic surfactants, and polymers such as polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethyl cellulose, and hydroxypropyl cellulose. Additives etc. can also be blended.

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

[Practical Examples 1 to 2, Comparative Examples 1 to 3] Eye drops having the formulations shown in Table 1 were prepared (all percentages in the table indicate sub-mouse/volume percentage), and their appearance and pH were examined. The results are also listed in Table 1.

The appearance of the eye drops is either cloudy or cloudy (
x) was rated i4' as an alternative.

Next, prepare and filter an eye drop with the prescription shown in Table 8182,
We investigated its antibacterial activity against imitative organisms, and based on its antibacterial activity, V5
Decaying power was determined. Antibacterial activity test method (body donation culture medium method)
l, 4, A2, PL77 (1973))
The results were expressed in terms of the time taken for the imitative organisms to die.

In addition, the preservative power was evaluated based on whether the preservative power was sufficient (0) or not sufficient (x).

From the results in Table 1, it can be seen that for threads containing sulfamethoxazole (a sulfa drug) and an organic amine, no clouding occurs even when benzalkonium chloride is added in an amount of 6 ppm or less. In addition, Table 2 shows that by using benzalkonium ifa in combination with barahydroxylated and butyl fragrant, even if the amount of benzalkonium chloride used is as low as 5 ppm, it is noticeable and sufficient. It was discovered that it has antiseptic properties.

Example An eye drop having the same formulation as Actual M# let 1 was prepared, except that benzethonium chloride was used instead of benzalkonium chloride.

The preservative power of this eye drop is sufficient as in Example 1.
It was worth it.

Example Eye drops with the following formulation were prepared.

Sulfamethoxazole 4% Monoethanolamine 0.99//Parahydroxybenzene methyl 0.026//Propyl parahydroxybenzoate 0.014//Benzalkonium chloride 5 1) I) ml Water
Remaining 100% I) H8,25 The preservative power of this eye drop was also sufficiently satisfactory as in Example 1.

Applicant: Lion Corporation Agent: Patent Attorney Takashi Kojima 2

Claims (1)

[Scope of Claims] 1. An ophthalmic solution comprising an ophthalmic solution containing a sulfa drug and a shelled amine, mixed with a quaternary ammonium salt Tobara hydroxybenzoic acid alkyl ester. 2. The amount of quaternary ammonium salt is 2 to 6 ppIn.
The ophthalmic solution according to the range 1rM of Machiken ml.