JPH02196718A - Liquid for external use - Google Patents

Abstract

PURPOSE:To obtain a liquid for external use having increased solubility and stability, containing indomethacin and a dissolution auxiliary as essential components. CONSTITUTION:0.1-5wt.% indomethacin and 0.3-10wt.% dissolution auxiliary are dissolved in a solvent such as an alcohol, an alcohol-water mixed base or a glycol to give a liquid for external use. One or more are selected from limonene, pinene, camphene, cymene, citronellol, geraniol, nerol, linalool, terpineol, rhodinol, borneol, isoborneol, menthone, camphor, thymol, safrole, isosafrole, eugenol and isoeugenol as the dissolution auxiliary. Indomethacin is an excellent non-steroid-based analgesic antiinflammatory drug.

Description

[Detailed description of the invention] The present invention relates to a novel topical solution of indomethacin.

Indomethacin is an excellent non-steroidal analgesic and anti-inflammatory agent, but it is almost insoluble in water and various solvents that can be used as a topical base, and slightly soluble in benzyl alcohol, tetrahydrofuran, dimethyl sulfoxide, dimethyl formamide, etc. However, since there are problems in terms of quantity and quality in making it into an external preparation, it has generally been administered in the form of an oral preparation.

In our research into external preparations for indomethacin, we first succeeded in obtaining a topical preparation with excellent skin absorption by incorporating indomethacin into an alcoholic aqueous system to make a gel ointment, and we would like to apply for a patent. Kosho 56-1088
No. 6). This gel ointment has recently been put on the market and has received high praise in clinical practice.

Furthermore, as a result of intensive research aimed at developing new dosage forms and bases for topical indomethacin, the present inventors found that certain terpenoids or phenols have been shown to improve the solubility and stability of indomethacin in various solvents. The present invention has been completed based on the discovery that the

Therefore, the present invention provides the following components (A) and (B), (A)
Indomethacin 0.1-5% by weight (B) Limonene, pinene, camphene, cymene, citronellol, geraniol, nerol, linalool, terpineol, rhodinol, borneol, isoborneol, menthone, camphor, thymol, safrol, isosafrol, eugenol and iso The present invention provides a liquid preparation for external use containing as an essential component 10% by weight of one or more solubilizing agents selected from the group consisting of eugenol.

In the present invention, the solubilizing agent can be used alone or in combination of two or more, and the blending amount varies depending on the amount of indomethacin and the type and amount of the solvent, but is generally 0.
A loading of 3-10% by weight achieves the objective.

In addition, as a solvent for dissolving indomethacin,
Alcohols such as ethanol and propatool; Alcohol-water mixture systems: Glycols such as butylene glycol and propylene glycol; Vegetable oils such as olive oil and soybean oil; Liquid higher fatty acids such as oleic acid, linoleic acid, and lilunic acid: Higher alcohols such as octyl alcohol and hexadecyl alcohol; Hydrocarbons such as paraffin and squalane; C4 to CI4 monocarboxylic acids, esters with ~C3 alcohols, C4 to CIG dicarboxylic acids and 01 to C5 Examples include diesters with alcohol.

The external liquid preparation of the present invention is produced by dissolving indomethacin in the above-mentioned solvent together with a solubilizing agent. The amount of indomethacin blended at this time is preferably 0.1 to 5% by weight.

As mentioned above, when a small amount of the solubilizing agent of the present invention is added, the solubility and stability of indomethacin in various solvents are significantly increased, so that various liquid preparations for external use can be prepared.

Next, an experimental example will be given and explained.

Experimental Example 1 Indomethacin dissolution test An excess amount of indomethacin was added to various solvents, and the amount of solubilizing agent shown in Table 1 was further added, followed by shaking at 25° C. for 24 hours, followed by centrifugation to collect the supernatant. The amount of indomethacin in this supernatant was measured by the UV method or the HPLC method, and compared with that in which no solubilizing agent was added. The results are shown in Table 1.

The following margin procedural amendment (voluntary) November 1989 Commissioner of the Japan Patent Office Yoshi 1) Tsuyoshi Bun Patent application 2 submitted on October 17, 1989, name of invention topical liquid 3, relationship with the case of the person making the amendment Applicant name: Kowa Co., Ltd. 4, agent address: 1-3-6, Nihonbashi Ningyocho, Chuo-ku, Tokyo
103) Day 6, Column 7 of "Detailed Description of the Invention" of the specification to be amended, Contents of the amendment (1) In the description, page 4, line 18, "Experimental Examples", followed by "and pharmaceutical preparations" Insert example.

(2) Page 6, bottom line After "Table 1", change the line and insert the legal text.

[Formulation Example 1 Indomethacin 1.0 (wt%) Limonene 2.0 Ethanol 50.0 Diisopropaturamine 0.5 Purified water Total 100.0 Indomethacin and limonene were added and dissolved in ethanol, and diisopropatol was added to the solution. Add purified water with amine dissolved in it to make a liquid.

Formulation Example 2 Indomethacin 0.5 (wt%) Linalool 5.0 Inpropatul
60.0 Triethanolamine 0.
3. Purified water Total 100.0 Indomethacin and linalool are added to isopropanol and dissolved, and purified water in which triethanolamine is dissolved is added to make a solution.

Formulation Example 3 Indomethacin 0.8 (wt%) Camphor 3.0 Isopropatol
55.0 Ammonia water (10%) 0.2 Purified water Total 100.0 Indomethacin and camphor are added to isopropanol and dissolved, and purified water in which aqueous ammonia is dissolved is added to prepare a solution.

Formulation Example 4 Indomethacin 0.1 (wt%) Camphor 1.0 Limonene
2.0 ethanol 90
．． 0 Purified water Total 100.0 Indomethacin, camphor, and limonene are added to ethanol and dissolved, and purified water is added to this to make a solution. ”

Claims (1)

[Claims] 1. The following components (A) and (B) (A) 0.1 to 5% by weight of indomethacin (B) limonene, pinene, camphene, cymene, citronellol, geraniol, nerol, linalool, terpineol, rhodinol, borneol, isoborneol, menthone, camphor, thymol, safrole,
One or more solubilizing agents selected from the group consisting of isosafrole, eugenol and isoeugenol 0
．． A liquid preparation for external use, characterized in that it contains 3 to 10% by weight as an essential component.