JPH0129170B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an ophthalmic solution containing a sulfur drug such as sulfamethoxazole, and more specifically to an ophthalmic solution containing a sulfur drug with excellent preservative power. Conventionally, it has been known to incorporate sulfur drugs such as sulfur amethoxazole into eye drops, and in order to impart preservative power to this type of sulfur drug-containing eye drops, parahydroxybenzoic acid such as butyl parahydroxybenzoate is added. It is also known to add alkyl esters. However, the preservative power of the sulfur drug-containing eye drops to which parahydroxybenzoic acid alkyl ester was added was not high and was extremely insufficient. In this case, increasing the amount of parahydroxybenzoic acid alkyl ester added has problems in terms of solubility, eye irritation, etc. When ammonium salts are added, they interact with sulfur drugs such as sulfamethoxazole, making the system cloudy, and chlorobutanol has a pH of 7 due to the solubility of ophthalmic solutions containing sulfur drugs such as sulfamethoxazole. Since it is high (more than .5), the decomposition rate of chlorobutanol is fast and it cannot be blended. Therefore, it has been desired to effectively increase the preservative power of sulfur 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 sulfur drugs, and as a result, they added chloride as a quaternary ammonium salt to a system in which alkanolamines are added to sulfur drugs. When benzalkonium and/or benzethonium chloride is blended at 0.002 to 0.02% by weight/volume based on the total amount of components, and when a hydrophilic nonionic surfactant is blended at 0.05 to 0.5% by weight/volume based on the total amount of components. It was discovered that the above-mentioned quaternary ammonium salt is solubilized and provides a transparent system without causing cloudiness, and that this eye drop has extremely high preservative power, which led to the creation of the present invention. It is something. The present invention will be explained in more detail below. The eye drops according to the present invention contain a sulfur drug, an alkanolamine, a quaternary ammonium salt, and a hydrophilic nonionic surfactant. Here, examples of sulfur drugs include sulfamethoxazole, sulfisoxazole, etc.
One or more of these may be used. The amount of these sulfur drugs is not particularly limited, but it is usually 3 to 5% (weight/volume%, the same hereinafter) of the total eye drops.Alkanolamines include monoethanolamine, diethanolamine, triethanolamine, etc. One or more of these are used.The blending amount is such that the molar ratio of sulfur agent and alkanolamine is 1:0.9 to 1:1.2.
In particular, it is preferable to use an amount in the range of 1:1 to 1:1.1, and by using the alkanolamine in the above range, it is possible to solubilize the sulfur drug, and also to reduce the amount of quaternary ammonium salt and hydrophilic agent. It provides excellent preservative power together with a nonionic surfactant. The pH of the ophthalmic solution of the present invention, which is a sulfur drug and an alkanolamine added thereto, is preferably 7.5 to 9.0; if the PH is too low, the solubility of the sulfur drug decreases and precipitation occurs, and if the PH is too high, the ophthalmic solution In some cases, the stability of the product may be impaired. The eye drops of the present invention contain a quaternary ammonium salt and a hydrophilic nonionic surfactant in a system containing a sulfur agent and an alkanolamine, thereby making it possible to obtain an eye drop that is transparent and has remarkable preservative power. can. Here, as the quaternary ammonium salt, benzalkonium chloride and/or benzethonium chloride is used. In addition, as hydrophilic nonionic surfactants, polyoxyethylene sorbitan monofatty acids such as polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, polyoxyethylene monostearate, Examples include hydrophilic ones such as polyoxyethylene monofatty acids such as polyoxyethylene monooleate and polyoxyethylene monopalmitate, and polyoxyethylene alcohol ethers such as polyoxyethylene lauryl ether. More than one species 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 amount of the quaternary ammonium salt is the amount that is soluble in the eye drops, and the type and amount of the sulfur agent, alkanolamine, and nonionic surfactant,
Although it varies depending on the type of quaternary ammonium salt, 0.002 to 0.02% of the total, preferably 0.005 to 0.02% of the total
It shall be 0.015%. When the amount is less than 0.002%, sufficient preservative power cannot be obtained, and when it is more than 0.02%, there is a problem in terms of safety. In addition, the amount of hydrophilic nonionic surfactant is
The content is 0.05-0.5%, preferably 0.05-0.2%. When the amount of the hydrophilic nonionic surfactant is less than 0.05%, the eye drops become cloudy, and when it is more than 0.5%, the usability is poor. The eye drops of the present invention may further include dipotassium glycyrrhizinate, diphenhydramine hydrochloride, potassium aspartate, in addition to the sulfur agent, as necessary.
Aminoethyl sulfonic acid, ε-aminocaproic acid, chlorpheniramine maleate, neostigmine methyl sulfate, etc. can be blended, and isotonizing agents such as sodium chloride and potassium chloride, polyhydric alcohol, polyvinyl alcohol, polyvinyl pyrrolidone, hydroxyethyl cellulose,
Polymer additives such as hydroxypropyl cellulose can also be blended. 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 were prepared (in the table, all percentages indicate weight/volume %), and their preservative power was evaluated based on their appearance and antibacterial activity against various microorganisms. I looked into it. The results are also listed in Table 1. The appearance is evaluated based on whether the eye drops are transparent (○) or cloudy (x), and the antibacterial activity test is performed using Ishizeki's preservative ability test method (liquid culture medium method).
[Pharmaceutical Research (Japan Official Publications Association) Vol.4, No.2,
P177 (1973)], and the results were expressed as the time taken to kill the microorganisms. The preservative power was evaluated based on whether the preservative power was sufficient (○) or not sufficient (x).

[Table] From the results in Table 1, it was found that a system containing a sulfur agent (sulfamethoxazole) and an alkanolamine was combined with a quaternary ammonium salt (benzalkonium chloride) and a hydrophilic nonionic surfactant (polyoxyethylene sorbitan). It has been found that by blending in combination with monooleate), an eye drop that is transparent and has excellent preservative power can 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 (=40) was used instead of polysorbate 80. This eye drop also had the same effect as Example 3. Examples 5 and 6 In the formulation of Example 1, an eye drop containing 0.5% polysorbate 80 (Example 5) and an eye drop containing 0.05% polysorbate 80 (Example 6) were used, respectively. Prepared. These eye drops also had the same effects as in Example 3.

Claims (1)

[Claims] 1. In eye drops containing sulfur drugs and alkanolamines, benzalkonium chloride and/or
Or benzethonium chloride based on the total amount of ingredients.
In addition to blending 0.002 to 0.02% by weight/volume, the amount of hydrophilic nonionic surfactant is 0.05 to 0.05% to the total amount of ingredients.
An eye drop characterized by containing 0.5% by weight/volume.