JPH0624986A - Composition for percutaneous absorption preparation containing eperisone or its salt and percutaneous absorption preparation - Google Patents

Abstract

PURPOSE:To obtain a medicine capable of providing highly therapeutic effects caused by eperisone or its sail after percutaneous absorption even to a small skin area. CONSTITUTION:This composition for percutaneous absorption preparation comprises eperisone or its salt, isopropyl myristate and a 10-20C aliphatic alcohol.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a composition for percutaneous absorption preparation containing eperisone or a salt thereof and a percutaneous absorption preparation.

[0002]

2. Description of the Related Art Eperisone and its salts are known as central muscle relaxants for alleviating abnormal muscle tone caused by diseases such as humeral shoulder syndrome and low back pain.
Currently administered orally. However, long-term administration is required to obtain a sufficient muscle tone relieving effect with eperisone or its salt, and oral administration requires three times a day to be taken. Even for the administration side, there is a problem that compliance is a problem. Further, long-term administration of eperisone or a salt thereof by oral administration causes a problem of causing gastrointestinal disorders. So, in recent years,
The development of dosage forms that can be expected to last for a long period of time with a single application has been promoted. In particular, transdermal preparations that are administered via the skin do not cause gastrointestinal disorders and are easy to apply. Started to get attention from.

[0003]

However, since the skin is also a protective film for protecting the living body from the external environment, it is generally not easy to absorb the drug through the skin, and the therapeutic effect of eperisone or its salt is not so great. In order to obtain by application of eperisone or its salts to an area, it is necessary to develop a base that promotes drug skin permeability of eperisone or its salts.

[0004]

Means for Solving the Problems As a result of various studies in view of the above situation, the present inventor has found that isopropyl myristate and carbon can be used as a base for a percutaneous absorption preparation containing eperisone or a salt thereof as an active ingredient. It has been found that a high skin permeation rate of eperisone or a salt thereof can be obtained when used in combination with an aliphatic alcohol having 10 to 20 atoms.

The present invention has been invented based on the above findings, and an object thereof is to provide a composition for transdermal absorption preparation and a transdermal preparation capable of effectively administering eperisone or a salt thereof through the skin, (1) Eperisone or a salt thereof, isopropyl myristate and 10 carbon atoms
To 20 aliphatic alcohols in the composition for percutaneous absorption preparations, and (2) a rubber-based pressure-sensitive adhesive, eperisone or a salt thereof, isopropyl myristate and 10 to 10 carbon atoms. The present invention relates to a percutaneous absorption preparation containing 20 aliphatic alcohols.

10 to 20 carbon atoms used in the present invention
As the aliphatic alcohol of, all the aliphatic alcohols having 10 to 20 carbon atoms that can be used as a pharmaceutical additive, for example, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol or oleyl alcohol, but preferably , Lauryl alcohol or myristyl alcohol, particularly preferably lauryl alcohol is used. The aliphatic alcohol having 10 to 20 carbon atoms may be used alone or in 2
It is also possible to use a combination of two or more species. The amount used is 0.01 with respect to 1 part of eperisone or its salt.
~ 400 parts, preferably 0.05 to 10 parts, especially 0.1
~ 3 parts.

In the present invention, isopropyl myristate is 0.01 part with respect to 1 part of eperisone or a salt thereof.
~ 400 parts, preferably 0.05 to 10 parts, especially 0.1
~ 3 parts used.

The dosage form of the percutaneous absorption preparation in which the composition for percutaneous absorption preparation of the present invention is used includes, for example, an ointment, a cream or a tape, and particularly preferable one is a rubber-based pressure-sensitive composition. It is a tape agent using an adhesive.

As the rubber pressure-sensitive adhesive, all rubber pressure-sensitive adhesives used for medical purposes, for example, styrene-butadiene-styrene block copolymer, styrene-isoprene-styrene copolymer, styrene-ethylene. / Butylene-styrene block copolymer or natural rubber-based polymer can be mentioned, preferably styrene-butadiene-styrene block copolymer or styrene-isoprene-styrene copolymer, particularly preferably styrene-isoprene-styrene copolymer. It is a polymer.

A percutaneous absorption preparation in the form of a tape using a rubber-based pressure-sensitive adhesive is prepared by a general method for producing a tape, for example, a solvent casting method, that is, eperisone or a salt thereof, isopropyl myristate and carbon. Producing by applying a solvent-containing rubber-based pressure-sensitive adhesive containing an aliphatic alcohol having 10 to 20 atoms, that is, a rubber-based pressure-sensitive adhesive stock solution onto a backing film (lining film) and drying. You can At that time, the coating thickness of the rubber-based pressure-sensitive adhesive stock solution is 10 to 500 μm, preferably 30 to 300 μm, and particularly preferably 50 to 200 μm.
m. Backing film for coating (lining film)
As the material, any material can be used as long as it does not cause any problems during the tape manufacturing process and the application of the rubber-based pressure-sensitive adhesive stock solution. For example, paper, non-woven fabric, cloth, polyethylene, polypropylene, polyvinyl chloride. Alternatively, polyethylene terephthalate can be used, but polyethylene, polypropylene or polyethylene terephthalate is preferable, and polyethylene terephthalate is particularly preferable.

The surface of the percutaneously absorbable preparation on which the rubber-based pressure-sensitive adhesive is exposed is covered with a release paper if necessary. As the release paper, any material that is generally used can be used, and examples thereof include surface-treated paper, metal or polymer film, and preferably paper whose surface is treated with silicone. Alternatively, it is a polymer film.

A substance for adjusting the adhesive force of the percutaneous absorption preparation of the present invention to the skin, such as rosin ester or liquid paraffin, can be added to the rubber-based pressure-sensitive adhesive stock solution, and eperisone is also added. Alternatively, a suitable stabilizer such as sodium thiosulfate or dl-α-tocopherol may be added to ensure the stability of the salt.

The content of eperisone or its salt in the percutaneously absorbable preparation of the present invention is 0.1 to 4 per cm ² of the preparation.
0 mg, preferably 0.5 to 20 mg, particularly preferably 1 to 10 mg, and the content of the aliphatic alcohol having 10 to 20 carbon atoms is 0.1 to 40 m per 1 cm ² of the preparation.
g, preferably 0.5 to 20 mg, particularly preferably 1 to
The content of 10 mg and isopropyl myristate is 0.1 to 40 mg, preferably 0.5 to 20 mg, and particularly preferably 1 to 10 mg per 1 cm ² of the preparation.

A typical example of the method for producing the percutaneous absorption preparation of the present invention is as follows: Prepared by dissolving 30 parts of styrene-isoprene-styrene block copolymer and 20 parts of rosin ester in 50 parts of toluene. 100 g of eperisone hydrochloride per 1 g of the mixture after drying in the prepared pressure-sensitive adhesive stock solution
g, 30 mg of lauryl alcohol, 50 mg of isopropyl myristate, 150 mg of liquid paraffin and 2 mg of sodium thiosulfate were added and mixed, and the resulting mixture was dried using an applicator to have a thickness of 150 μm.
On a polyethylene terephthalate film and dried.

[0015]

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited thereto.

Example 1 The composition before drying was the composition shown in Table 1, and a styrene-isoprene-styrene block copolymer and a rosin ester were dissolved in toluene to prepare a pressure-sensitive adhesive stock solution. To the adhesive stock solution, eperisone hydrochloride, optionally lauryl alcohol, isopropyl myristate and liquid paraffin, and sodium thiosulfate were added and mixed, and the resulting mixture was dried using an applicator to have a thickness of 150 μm. Sample 1 of the present invention and Comparative Samples 1 to 4 were prepared by coating on a polyethylene terephthalate film in such a manner as described above and drying.

Table 1 Ingredients of the present invention Comparative sample Comparative sample Comparative sample Comparative sample Sample 1 1 2 3 4 ───────────────────────────── ──────── Eperisone hydrochloride 10 10 10 10 10 Styrene-isoprene 20 27 23 26 21-Styrene copolymer Rosin ester 13 18 15 17 14 Toluene 33.8 44.8 38.5 43.8 34.8 Liquid paraffin 15 0 13.3 0 15 Lauryl alcohol 300 0 3 0 Isopromyristate 500 500 Pils sodium thiosulfate 0.2 0.2 0.2 0.2 0.2 The following experiments were performed using these samples.

The skin of the abdomen extracted from the hairless rat was sandwiched between vertical diffusion cells (effective permeation area: 1 cm ² ), 4.5 ml of water was placed in the dermis side cell, and the mixture was stirred at 37 ° C. The sample 1 of the present invention or the comparative samples 1 to 4 was applied to the stratum corneum, the amount of eperisone hydrochloride transferred to the dermis side with time was measured, and the cumulative skin permeation amount and the maximum skin permeation rate for 24 hours were obtained. The results are shown in Table 2.

Table 2 Present invention Comparative sample Comparative sample Comparative sample Comparative sample Sample 1 1 2 3 4 ────────────────────────────── ─────── 24-hour cumulative skin permeation 24 6 5 9 13 (μg / cm ² ) Maximum skin permeation rate 476 110 76 161 242 (μg / cm ² / h) Clear from the results shown in Table 2. Thus, Comparative Samples 3 and 4 containing lauryl alcohol and isopropyl myristate, respectively, had better skin permeation than Comparative Sample 1 containing none of these components and Comparative Sample 2 containing liquid paraffin in place of these components. Sample 1 of the present invention, which exhibits a promoting action and contains both lauryl alcohol and isopropyl myristate, was compared with Comparative Samples 3 and 4 in both cumulative skin permeation amount and maximum skin permeation rate for 24 hours. Provide an advantage over the combination of lauryl alcohol and isopropyl myristate, it can be seen that a synergistic effect in percutaneous absorption promoting effect of eperisone or a salt thereof.

[0020]

As is apparent from the above description, according to the present invention, a composition for percutaneous absorption preparation of eperisone or a salt thereof and a percutaneous absorption preparation showing a high skin permeation rate are provided. A high therapeutic effect of eperisone or its salt can be obtained even by transdermal administration to a small skin area.

Claims (2)

[Claims] 1. A composition for percutaneous absorption preparation, which comprises eperisone or a salt thereof, isopropyl myristate and an aliphatic alcohol having 10 to 20 carbon atoms. 2. A percutaneous absorption preparation, which comprises eperisone or a salt thereof, isopropyl myristate, and an aliphatic alcohol having 10 to 20 carbon atoms in a rubber pressure-sensitive adhesive.