JPH0338246B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a poultice characterized by containing N-acyl lysine.

BACKGROUND ART Conventionally, therapy has been carried out by applying poultices to the affected area for the purpose of treating inflammation such as bruises, sprains, arthritis, rheumatoid arthritis, and muscle pain. These plasters mainly contain inorganic powder excipients such as bentonite, kaolin, talc, diatomaceous earth, light anhydrous silicic acid, and zinc oxide, as well as methyl salicylate, glycol salicylate, menthol, camphor, eucalyptus oil, thymol, and diphenhydra. It is prepared by adding drugs such as mint, nicotinic acid benzyl ester, capsaicin, peppermint oil, borneol, hormones, and vitamins and kneading it with water or an aqueous liquid such as glycerin, either as it is or spread on a sheet such as cloth. It is used in

Such poultices have the following properties: (1) They have good adhesion to the skin and can reliably follow the expansion and contraction of the skin, and (2) The medicine does not deteriorate during storage and has excellent storage and specific efficacy. (3) characteristics such as not inhibiting physiological functions of the skin such as skin respiration and water evaporation and having high safety are required.

However, the above-mentioned plasters prepared by kneading an inorganic powder excipient and a drug with an aqueous liquid lack adhesion to the skin, causing peeling during use, or due to the high surface of the inorganic powder excipient. Problems have been pointed out that due to activity and pH, coexisting drugs may denature and decompose during storage, resulting in decreased drug efficacy or that drugs may induce dermatitis.

Various attempts have been made to improve these drawbacks. For example, a method of improving adhesion to the skin by incorporating water-soluble polymers or N-acylamino acid amides (Japanese Unexamined Patent Application Publication No. 1983-1999)
No. 20715, No. 55-2646), a method of alleviating skin irritation by using adrenal extract as a drug (Japanese Patent Application Laid-open No. 55-62014), or using higher aliphatic carboxylic acids, γ-oryzanol, etc. Examples include a method of improving the stability of drugs by blending them (Japanese Patent Application Laid-open Nos. 55-79318 and 59-53415).

However, when water-soluble polymers are used, their adhesion to the skin is too strong, inhibiting physiological functions such as skin respiration, and often causing rashes, etc. When using N-acylamino acid amides, etc. , water, glycerin, alcohol, and other polar liquids, a new problem arises in that the heat absorption effect is reduced and the refreshing feeling is lacking. Furthermore, when adrenal gland extract is used as a drug, although it is less irritating to the skin than other drugs, it has poor stability under alkaline conditions.
It has the disadvantage that it is difficult to use in combination with commonly used alkaline inorganic powder excipients such as kaolin and talc. On the other hand, when blending higher aliphatic carboxylic acids or γ-oryzanol, although it is effective to some extent in improving the storage stability of the drug, it is not very effective in improving the adhesion to the skin, and the various effects mentioned above still occur. The reality is that no poultice that fully satisfies the properties has been obtained.

In view of these circumstances, the present inventors have made extensive studies to develop a poultice with the above-mentioned required properties.The inventors have found that by incorporating an acylated product of lysine, which is a type of amino acid, adhesiveness to the skin has been improved. The present inventors have discovered that it is possible to obtain poultices that have excellent drug storage stability and are mild and less irritating to the skin, leading to the completion of the present invention.

That is, the present invention relates to a poultice characterized by using at least one type of N-acyl lysine represented by the following general formulas (1) to (3).

(However, in general formulas (1) and (2), RCO represents an aliphatic acyl group having 8 to 22 carbon atoms, and in general formula (3), R′CO and R″CO each represent a carbon number of 1 ~22
represents an aliphatic acyl group whose total number is 9 to 44. ) To obtain N〓,N〓-diacyllysine represented by the general formula (3) above, fatty acid chloride is dropped into an alkaline aqueous solution of lysine, which is called SCHOT.
A TEN BAUMANN reaction is used. At this time, if the amino group at the α-position or ε-position is protected in advance, compounds (1) and (2) in which only the ε-position or α-position is selectively acylated can be obtained. I can do it. Compound (1) can also be obtained by heating and dehydrating an equimolar salt of lysine and fatty acid, and compound (3) a double molar salt at a temperature of 100°C to 250°C. 51-28610).

Examples of N-acyl lysine in the present invention include N〓-(2-ethylhexanoyl)lysine, N〓
−Oleoyl lysine, N〓−octanoyl lysine,
N〓-decanoirisine, N〓-lauroyl lysine,
N〓-myristoyl lysine, N〓-palmitoyllysine, N〓-stearoyl lysine, N〓-(2-ethylhexanoyl)lysine, N〓-oleoyl lysine, N〓-octanoyl lysine, N〓-decanoyl lysine , N〓-lauroyllysine, N〓-myristoyllysine, N〓-palmitoyllysine, N〓-stearoyllysine, N〓-lauroyl-N〓-stearoyllysine, N〓-hexanoyl-N〓-palmitoyllysine, N〓, N〓-dilauroyl lysine,
In addition to N〓, N〓-dioctanoyl lysine, mixtures thereof can be mentioned. In addition, these N-acyl lysines can be used in the same way whether they are optically active forms or racemic forms.

Conventionally, N-acyl lysine or its metal salt has been used as an amphoteric surfactant in detergents (Japanese Patent Application Laid-open No. 50-97605
It is known that it is used as a stabilizer for halogen-containing resins such as polyvinyl chloride (Japanese Patent Application Laid-Open No. 12847/1984), but the present inventor has not investigated its use as a base for poultices. It was first discovered by et al.

As is clear from its structure, the N-acyl lysine of the present invention is composed of naturally derived lysine and fatty acids, and has an amide group like skin proteins, so it is less irritating to the skin and exhibits excellent adhesion. In addition, since it has a hydrocarbon chain, which is a hydrophobic group, in its molecule, it has a high affinity with oily bases and contributes to sustained release and stabilization of drugs. In particular, N-
Acyl lysine exhibits a weakly acidic PH and lowers the PH of alkaline inorganic powder excipients such as kaolin and talc, so it is effective in stabilizing drugs that have conventionally been difficult to use in combination with such excipients. Furthermore, the N of the present invention
- Poultices using acyl lysine are characterized by improved wettability of inorganic powder excipients and high moisture retention.

The poultice according to the present invention can be prepared by a method in which N-acyl lysine and an inorganic powder excipient are pre-blended and then a drug is added and kneaded, or a method in which N-acyl lysine and a drug are pre-blended and then an inorganic powder excipient is added and kneaded. However, there is no problem in adding other ingredients such as a PH adjusting agent, thickener, oil agent, etc. as necessary. In addition, it can be used by spreading it on a sheet of cloth or the like, or by spreading the paste on a sheet in advance and attaching a protective film such as polyethylene to the surface if necessary. A method of peeling off and applying the adhesive may be used as appropriate.

A more detailed explanation will be given below using examples.

Example 1 Salicylic acid methyl ester 0.5 wt% Thymol 0.1 Peppermint oil 0.5 Glycerin 25.0 N-Lauroyl lysine 5.0 Kaolin 45.0 Purified water Remaining total 100.0 wt% Based on the above recipe, N-Lauroyl lysine and kaolin were made into a paste with purified water and glycerin. After kneading, thymol, peppermint oil, and methyl salicylic acid ester were added to prepare a poultice. Such poultices have excellent adhesion to the skin and safety, as well as excellent storage stability.

Example 2 Gelatin 7.0 wt% Dialdehyde starch 0.7 N-palmitoyllysine 5.0 Zinc oxide 5.0 Glycerin 10.0 Polyvinyl alcohol 5.0 Sodium polyacrylate 0.5 Citric acid 0.5 Indomethacin 0.5 Purified water Remaining total 100.0 wt% Poultices prepared according to the above formulation were , indomethacin has excellent storage stability and low skin irritation.

Example 3 Salicylic acid methyl ester 0.5wt% Salocol 0.2 L-menthol 0.3 DL-camphor 0.5 N〓,N〓-dilauroyl lysine 5.0 Kaolin 30.0 Bentonite 10.0 Sorbitol (70%) 30.0 Citric acid 0.3 Purified water Remaining total 100.0wt% Above Prescription poultices have excellent long-lasting medicinal effects and safety due to their adhesion to the skin.

Claims (1)

[Scope of Claims] 1. A poultice containing at least one type of N-acyl lysine represented by the following general formulas (1) to (3). (However, in general formulas (1) and (2), RCO represents an aliphatic acyl group having 8 to 22 carbon atoms, and in general formula (3), R′CO and R″CO each represent a carbon number of 1 ~22
represents an aliphatic acyl group whose total number is 9 to 44. )