JPH0461847B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an indomethacin topical preparation containing indomethacin as an active ingredient. Indomethacin is widely used as a non-steroidal anti-inflammatory analgesic, but it has the disadvantage that it is poorly soluble in water and common media, and its stability depends on the choice of base. Therefore, the present inventors conducted intensive research to provide a stable external preparation of indomethacin, and as a result,
The present inventors have discovered that the object of the present invention can be achieved by blending indomethacin into an aqueous base containing boric acid and/or a boric acid metal salt, and maintaining the pH within an appropriate range, and have thus arrived at the present invention. . That is, the gist of the present invention is a topical indomethacin preparation prepared by incorporating indomethacin into an aqueous base containing boric acid and/or a boric acid metal salt, and adjusting the pH to 4.5 to 6.5. Hereinafter, the present invention will be explained in detail. First, the base in the present invention is aqueous and contains boric acid and/or a boric acid metal salt. Examples of boric acid metal salts include salts of alkali metals such as sodium and potassium, and alkaline earth metals such as calcium and magnesium, but borax is preferably used. The aqueous base used in the present invention contains water such as purified water and distilled water, and includes, for example,
Ointments can be made into a gel by adding a suspending agent (gelling agent) to water, or oil-in-water (o/w) or oil-in-water (o/w) or oil-in-water (o/w) by emulsifying oil and fat components and water in the presence of an emulsifier. A water-in-water (w/o) emulsion type is used, and as a lotion, a suspension type, an emulsion type, or a solution type is suitably used. When preparing these bases, oil and fat components, emulsifiers, dispersants, suspending agents (gelling agents), etc. commonly used in cosmetics or pharmaceutical external preparations are appropriately selected depending on the type of the intended external preparation. and can be used. Examples of oil and fat components include hydrocarbons such as liquid paraffin, petrolatum, and waxes, aliphatic higher alcohols such as stearyl alcohol, esters of higher fatty acids and higher alcohols such as beeswax and spermaceti, and isopropyl palmitate. Esters of higher fatty acids and lower alcohols, other vegetable and animal oils, etc. can be used. Any of anionic, cationic, and nonionic surfactants can be used as emulsifiers and dispersants, but it is preferable to use nonionic surfactants because they are less irritating to the skin. for example,
Examples include polyoxyethylene fatty acid esters such as polyoxyethylene stearate, sorbitan fatty acid esters such as sorbitan monolaurate, and polyoxyethylene higher alcohol ethers such as polyoxyethylene oleyl ether. Examples of the suspending agent (gelling agent) include carboxyvinyl polymer, methylcellulose, carboxymethylcellulose, hydroxyethylcellose, hydroxypropylcellulose, bentonite, and sodium alginate. Various additives can be further added to the above-mentioned base by conventional methods. Further, the blending amounts of various components in the base are appropriately determined depending on the purpose of the dosage form and the like. The amount of boric acid and/or boric acid metal salt in the external preparation is usually 0.05 to 5% by weight, preferably 0.05 to 0.5% by weight.
Weight%. The amount of indomethacin, which is the main ingredient, is usually 0.1 to 3% by weight, preferably 0.5 to 2% by weight. Depending on the intended dosage form, indomethacin can be dissolved and blended in oil and fat components, alcohols (ethanol, propylene glycol, polyethylene glycol, etc.), etc., or it can be blended in the form of a solid powder. The method for preparing the topical preparation of indomethacin according to the present invention is not limited, but for example, in the case of an ointment, indomethacin is stirred and dissolved in an alcohol such as ethanol and a fatty acid ester such as diisopropyl adipate. Preferably, a method is employed in which the preparation method is prepared by swelling the oxidizing agent) in glycerin and water, mixing these, and further mixing boric acid and/or boric acid metal salt dissolved in water. In addition, the pH of the external preparation of the present invention needs to be adjusted to a range of 4.5 to 6.5. The pH is adjusted by adjusting the amount of boric acid and/or boric acid metal salt to be blended. Furthermore, commonly used additives such as antioxidants, bactericides, vitamins, etc. can be added as necessary. The above antioxidants are preferably water-soluble ones, such as sodium bisulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid,
Examples include cysteine, thioglycerol, and particularly sodium bisulfite and sodium pyrosulfite are preferably used. Since the external preparation according to the present invention exhibits good stability over a long period of time, it can exhibit stable medicinal efficacy of indomethacin. EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, but the present invention is not limited to the following Examples unless it exceeds the gist thereof. Example Indomethacin 1.0g Ethanol 50.0g Carboxyvinyl polymer 1.4g Diisopropyl adipate 7.0g Glycerin 6.5g Borax 0.3g Sodium bisulfite 0.05g Purified water Amount to make a total of 100g Ointment with the above blending ratio was manufactured by the method consisting of the following steps. did. (PH: 5.2) A: Stir and dissolve the above in the mixture of above and above at 50° to 60°C. B Swell the above in the above and 30 g of water. C. Add the mixture obtained in step B above to the mixture obtained in step A above and stir until homogeneous. D Dissolve the above in 2.0 g of water and add to the mixture obtained in Step C above, then add the remaining amount of water and stir until the whole is homogeneous. Comparative Example In the above example, 1.2 g of diisopropanolamine was used instead of 0.3 g of borax.
An ointment was produced in exactly the same manner as in the example.
(PH: 6.4) Test Example The two types of ointments prepared in Examples and Comparative Examples were packed into a closed aluminum tube whose inner surface was coated with epoxy resin, and the two types of ointments prepared in Examples and Comparative Examples were packed in a closed aluminum tube whose inner surface was coated with epoxy resin, and the mixture was placed in a constant temperature bath at 70℃ for 2 hours.
After storage for a week, changes in the ointment's appearance and indomethacin content were confirmed.

[Table] As shown above, in the case of the ointment formulation of the present invention, 70℃2
Only slight changes in appearance and indomethacin content were observed even under very severe conditions of several weeks. On the other hand, in the comparative example, the color of the ointment itself changed to yellowish brown, and at the same time, the indomethacin content decreased.
A change of 40% decrease was observed.

Claims (1)

[Claims] 1. Indomethacin is added to an aqueous base containing boric acid and/or boric acid metal salt, and the pH is adjusted to 4.5-4.5.
Indomethacin topical preparation adjusted to 6.5.