JPS5936610A - Adhesive application pharmaceutical - Google Patents

Abstract

PURPOSE:An adhesive application pharmaceutical, prepared by incorporating a rubber type adhesive material with a drug active constituent and leaves of a majoram and nutmeg, and having improved stability of the drug active constituent by the synergistic action thereof. CONSTITUTION:An adnesive application pharmaceutical prepared by incorporating a rubber type adhesive material, e.g. a natural rubber, synthetic rubber, and further the third constituent, e.g. a tackifier on an adhesion and holding power adjusting agent, etc. and a drug active constituent and leaves of a majoram or an extract thereof and nutmeg or an extract thereof. The amount of the leaves of the majoram and nutmeg to be incorporated based on the weight of the adhesive material is 0.1-20wt%, preferably 0.5-5wt%, in the case of the leaves of the majoram and nutmeg, and 0.01-5wt%, preferably 0.02-2wt%, expressed in terms of a dried material, in the case of the extract. A compound containing a phenolic hydroxyl group, e.g. a salicyclic acid derivative or an amine type compound, e.g. an ethanolamine type antihistaminic agent, used as the drug active constituent is particularly effective.

Description

[Detailed description of the invention] The present invention relates to adhesive patch preparations.

Conventionally, drugs administered to the integument have been intended to locally act on the integument and its underlying tissues, such as sterilization, disinfection, and analgesia. However, in recent years, attempts have been made to administer drugs that have systemic effects into the integument, and the integumentary administration of various drugs has been proposed or attempted. Such drugs are usually administered to the skin by formulating them into adhesive patches, but if the medicinal ingredients are blended into a rubber adhesive and remain open for a long period of time, the medicinal ingredients may evaporate and decompose. The therapeutic efficacy of such preparations tends to be significantly reduced.

By the way, volatilization and photodecomposition of the drug are sealed using aluminum laminate packaging. This can be prevented by shielding from light, but the decomposition of drugs compounded in rubber adhesive substances, especially compounds containing phenolic hydroxyl groups, amine compounds, etc., continues to progress even when covered with aluminum laminate. However, there are many products that become unusable after being stored for two to three years. Therefore, it is desired to develop an adhesive patch preparation that is stable even when a drug, especially a phenolic hydroxyl group-containing compound, or an amine compound is blended with a rubber-based adhesive substance.

Under these circumstances, the present inventors have been conducting research to develop a rubber-based adhesive patch with excellent stability of medicinal ingredients, and have discovered that marjoram leaf (marjoram leaf extract) and nutmeg (nutmeg extract) have been developed. 0 under the heading that when used in combination with an adhesive patch made of a rubber-based adhesive substance, the stability of the medicinal ingredients contained therein increases.
The combined effect (synergistic effect) of marjoram leaf (marjoram leaf extract) and nutmeg (nutmeg extract) is as follows:
If either one of these is blended into a rubber-based adhesive patch, there is no stabilizing effect on the medicinal ingredient.
On the contrary, it is completely unexpected because the stability of the industry will be damaged.

The present invention was completed based on this completely unexpected finding, and provides an adhesive patch preparation comprising a rubber-based adhesive substance and a medicinal ingredient. and nutmeg extract as an essential ingredient.

In the present invention, marjoram leaves and nutmeg include:
Usually, dried powder is used, and as marjoram leaf extract and nutmeg extract, solvent,
In particular, an extract extracted with a nonpolar solvent, a low polar solvent, or a mixed solvent thereof, and especially a powder of a dry extract from which the solvent has been distilled off, is used.

Specific examples of the extraction solvent include alcohols IL Nuknol. (lower alcohols such as ethanol), ethers (e.g., diethyl ether, petroleum ether, etc.), ketones (e.g., lower ketones such as acetone), nitriles (e.g., acetone trile), water, and mixed solvents thereof. may be obtained by extracting marjoram leaves and nutmeg separately, or may be obtained by extracting a mixture of both at the same time.

The addition of marjoram leaves and nutmeg ii is about 0.01 to 5 weights, preferably about 0.02 to 2 weights as a rubber material.

In the above blending ratio, a sufficient stabilizing effect of the drug is maintained, there is no decrease in the adhesive strength of the rubber-based adhesive substance, and there is little medicinal odor. The ratio is usually l:20~
The ratio is 20:1, and the same blending ratio may be used for these extracts.

Regarding the present invention, the rubber-based adhesive substance is one that is generally used as a paste for adhesive patch preparations, and includes, for example, natural rubber, 9 synthetic rubber, mixtures thereof, and even those with a third component added thereto. Things can be given. The synthetic rubber is styrene-isoprene-styrene block copolymer rubber.

Examples include styrene-butadiene rubber, poly1ten rubber, polyisoprene rubber, butyl rubber, and silicone rubber. Examples of the third component include tackifiers such as terpene-based resins, oil-based resins, sulfur paraffin, and animal and vegetable oils (for example, Oli-1 oil).

Adhesion/holding strength adjusting agent for soybean oil, beef tallow, tonne fat), polygoutine, low-grade imprene, wax, etc.

Titanium oxide, zinc oxide, aluminum mekusilicate.

Fillers such as calcium sulfate and calcium phosphate.

water-containing emulsifiers (e.g., nlu and tanmonooleate,
Examples include sodium lauryl sulfonate), emulsifying aids (eg, magnesium stearate, aluminum stearate), and the like.

Regarding the present invention, the medicinal ingredient may be one that is absorbed transdermally with the aid of a transdermal absorption aid of rubbery viscosity, and may be either a topical drug or a total dual drug),
Examples include drugs for treating skin diseases, drugs that cause skin irritation, and drugs for treating indefinite complaints. In particular, the content of phenolic hydroxyl group-containing compounds and amine compounds decreases markedly in rubber-based adhesive substances when administered orally, so this invention 8A has particular significance when such unstable compounds are used as medicinal ingredients. . Examples of compounds containing phenolic hydroxyl groups include salicylic acid derivatives (fIJ monoglycol cylate, methyl salicylate, etc.), vitamin E7 and its derivatives, kabsaicin, and examples of amine compounds include ethanolamine antihistamines such as diphenhydramine. , ethylenediamine-based antihistamine drugs such as chlorpheniramine, etc. A specific medicinal ingredient with this ability is, for example, dt-camphor.

Cold-sensitive skin irritating drugs such as thymol and d-borneol, non-steroidal anti-inflammatory drugs such as indomethacin and cyclo-7enate sodium, steroidal anti-inflammatory drugs such as dexamethacin and becumetasone, hexidine diglyconate, acrinol Antibacterial agents such as chili pepper extract, nonylic acid vanillylamide, ginger extract, cannuri tincture, cantharidin and other heat-sensitive skin irritating drugs are used.

Hereinafter, the present invention will be explained in more detail with reference to Examples and Experimental Examples〇Example 1゜A phase: Impregnated rubber 45%C phase: Natural rosin 88.98% phase mixed with 201I + mastic at 180°C After cooling to 120° C., phase B was added and kneaded for 10 minutes. Further, while kneading, phase C is added and kneaded for 10 minutes, and while cooling to 80°C, phase D is added and kneaded for 5 minutes to obtain an adhesive patch. It means everything.

Example 2 Layer B in Example 1 was replaced with 5% dry powder of marjoram leaf ethanol extract and 5% dry powder of Mameg ethanol extract to obtain a nine-adhesive patch preparation.

Comparative Example 1 An adhesive patch preparation is obtained from the formulation in Example 1, with Phase B removed.

Comparative Example 2 An adhesive patch preparation is obtained in which Phase B of Example 2 is replaced with 10% ethyl alcohol extract of marjoram leaves.

Comparative Example 3 Phase B of Example 2 was replaced with IO% ethyl alcohol extract of Nummeg to obtain a 9-adhesive patch preparation.
Table 1 shows the results of investigating the drug survival rate in the case of Kezuki@J.

(hereinafter f, et al.) Table 1: Residual rate (%) of each drug Patent applicant: Nitto Electric Industry Co., Ltd. 58-

Claims (8)

[Claims] (1) An adhesive preparation comprising a rubber-based adhesive substance and a medicinal ingredient, which contains as essential ingredients at least one selected from marjoram leaf and marjoram leaf extract, and at least one selected from nutmeg and nutmeg extract. Gender patch preparation. (2) Adhesiveness according to claim (1), wherein the marjoram leaf extract and nutmeg extract are extracted from marjoram leaf or nutmeg, respectively, using at least one selected from a low polar solvent and a non-polar solvent. Patch preparation. (3) The solvent is water, ether, or ketone. The adhesive patch preparation according to claim (2), which is at least one selected from lower alcohols and acetonitrile. (4) The adhesive patch preparation according to claim 1, (2) or (3), wherein the medicinal ingredient is a phenolic hydroxyl group-containing compound. (5) The adhesive patch preparation according to claim (4), wherein the phenolic hydroxyl group-containing compound is at least one selected from salicylic acid and its derivatives, kabsaicin, and vitamin E and its derivatives. (6) The adhesive patch preparation according to Claims (1) and (2) or Fi(3), wherein the pharmacologically active substance is an amine compound. (7) The adhesive patch preparation according to claim (6), wherein the amine compound is an efnolamine antihistamine drug. (8) The adhesive patch preparation according to claim (6), wherein the Avan-based compound is an ethylenediamine-based antihistamine drug.