JPH11209269A - Cataplasm for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a cataplsm having high effects for periarthritis scapulo- numeralis, lumbago, etc., and capable of being easily used by disposing an adhesive agent layer containing a topical vasodilator and a muscle relaxant on one surface of a support. SOLUTION: This cataplasm for external use is obtained by disposing (B) an adhesive agent layer containing (i) a topical vasodilator, preferably a Guinea pepper extract, and (ii) a muscle relaxant such as chlorphenesin carbamate on one surface of (A) a laminated film comprising polyethylene terephthalate, etc., by a solvent coating method, etc. A preferable adhesive for the component B includes an acrylic pressure sensitive adhesive obtained by copolymerizing 2-ethylhexyl acrylate, etc., as a main component with vinyl pyrrolidone, hexamethylene dimethacrylate, etc. The components Bi and the component Bii are preferably contained in amounts of 0.02-2 wt.% and 0.1-20 wt.%, respectively, in the component B. The medicine is preferably used in the form of a tape preparation or a patch preparation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an external patch, and more particularly to an external patch containing a local vasodilator and a muscle relaxant.

[0002]

2. Description of the Related Art Many external preparations containing a local vasodilator as a drug are on the market, and are frequently used for treatment of, for example, bruises, periarthritis of the shoulder joint, and back pain. Particularly recently, patches have been developed for reasons such as ease of use, and many patches have been marketed with the aim of promoting blood circulation.

[0003] However, these patches are either a combination of a local vasodilator and an anti-inflammatory or analgesic such as glycol salicylate, methyl salicylate, glycyrrhizic acid, or a preparation containing only a local vasodilator. However, in the actual treatment of shoulder periarthritis, low back pain, etc., the above-mentioned topical patch containing local vasodilation is often inadequate, and oral muscle relaxants are used in combination for the purpose of further enhancing the effect. It is the present situation.

[0004] The combined use of the above-mentioned external patch and oral preparation is very inconvenient and causes a decrease in user compliance.

[0005]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an external patch containing a local vasodilator and a muscle relaxant in addition to an effect on shoulder periarthritis, back pain and the like. And to provide an external patch which is high in cost and easy to use.

[0006]

The patch for external use of the present invention comprises:
An adhesive patch for external use having an adhesive layer provided on one surface of a support, characterized in that the adhesive layer contains a local vasodilator and a muscle relaxant.

[0007] The external patch of the present invention may be used in any form such as a tape, a patch, a poultice, a plaster and the like, but a tape or a patch is preferred in view of simplicity in use. Different adhesives are used depending on the form of the external patch.

The pressure-sensitive adhesives used in the above-mentioned tapes, patches and plasters have high safety to the human body and have pressure-sensitive adhesive properties that can be applied to the skin for a long time at normal temperature (co). It is not particularly limited as long as it is a polymer, and for example, an acrylic adhesive, a rubber adhesive, a silicone adhesive, or the like can be used. However, it is preferable to use an acrylic pressure-sensitive adhesive or a rubber-based pressure-sensitive adhesive in consideration of the adhesive properties and cost.

As the acrylic pressure-sensitive adhesive, for example,
Mainly (meth) acrylic acid alkyl ester (co)
A polymer is preferably used, but a copolymer of the (meth) acrylic acid alkyl ester and a functional monomer copolymerizable therewith may be used.

Examples of the alkyl (meth) acrylate include ethyl (meth) acrylate, butyl (meth) acrylate, isobutyl (meth) acrylate, hexyl acrylate, 2-ethylhexyl (meth) acrylate, Octyl acrylate, isooctyl methacrylate, isodecyl acrylate, decyl methacrylate,
Examples thereof include lauryl (meth) acrylate and stearyl (meth) acrylate, which may be used alone or in combination of two or more.

Examples of the functional monomer include a monomer having a hydroxyl group, a monomer having a carboxyl group, a monomer having an amide group, and a monomer having a nitrogen-containing heterocyclic ring.

Examples of the monomer having a hydroxyl group include hydroxyalkyl (meth) acrylates such as 2-hydroxyethyl (meth) acrylate and hydroxypropyl (meth) acrylate. Examples of the monomer having a carboxyl group include, for example, α, β-unsaturated carboxylic acids such as (meth) acrylic acid; monoalkyl maleates such as butyl maleate;
(Anhydrous) maleic acid, fumaric acid, crotonic acid and the like.

The monomers having an amide group include:
For example, alkyl (meth) acrylamide such as acrylamide, dimethylacrylamide and diethylacrylamide; alkyl ether methylol (meth) acrylamide such as butoxymethylacrylamide and ethoxymethylacrylamide; and diacetone acrylamide.

Examples of the monomer having a nitrogen-containing heterocyclic ring include vinyl pyrrolidone and vinyl imidazole.

In addition to the above functional monomers, vinyl acetate,
Styrene, α-methylstyrene, vinyl chloride, acrylonitrile, ethylene, propylene, butadiene and the like can also be used.

The (co) polymer mainly composed of the (meth) acrylic acid alkyl ester is usually obtained by blending the above monomers in the presence of a polymerization initiator and performing solution polymerization. ) Alkyl acrylate is preferably contained in an amount of 50% by weight or more based on all copolymerized components. In the case of performing solution polymerization, a predetermined amount of various monomers is added with ethyl acetate or another polymerization solvent, and azobis-based, peroxide-based, etc. polymerization is started in a reactor equipped with a stirring device and a cooling reflux device. 70 in a nitrogen atmosphere in the presence of
What is necessary is just to make it react at -90 degreeC and 8-40 hours. Further, the monomer may be charged in a lump or divided.

Examples of the azobis-based polymerization initiator include 2,2-azobis-iso-butyronitrile,
Examples include 1′-azobis (cyclohexane-1-carbonitrile) and 2,2′-azobis (2,4-dimethylvalerinitrile). Examples of the peroxide-based polymerization initiator include lauroyl peroxide, Benzoyl peroxide, di (tert-butyl) peroxide and the like can be mentioned.

Examples of the rubber-based pressure-sensitive adhesive include natural rubber, synthetic isoprene rubber, polyisobutylene, polyvinyl ether, polyurethane, polyisoprene, polybutadiene, styrene-butadiene copolymer, styrene-
Those having an isoprene copolymer, a styrene-isoprene-styrene block (SIS) copolymer or the like as a main component are used.

As the above-mentioned silicone-based pressure-sensitive adhesive, those having a silicone rubber as a main component such as polyorganosiloxane are used.

Various additives may be added to the pressure-sensitive adhesive, if necessary. As the compounding agent, for example,
Tackifiers such as rosin resin, polyterpene resin, cumarone-indene resin, petroleum resin, terpene phenol resin, etc .; plasticizers such as liquid polybutene, mineral oil, lanolin, liquid isobutylene, liquid polyacrylate, etc .; fillers; Is mentioned.

When the external patch of the present invention is used as a poultice, the adhesive includes, for example, natural polymers such as sodium alginate, gelatin, corn starch and tragacanth; and cellulose-based materials such as methylcellulose, hydroxyethylcellulose and carboxymethylcellulose. Polymers; starch polymers such as dextrin and carboxymethyl starch; polyvinyl alcohol;
Sodium polyacrylate, methoxyethylene-maleic anhydride copolymer; synthetic polymers such as polyvinyl ether and polyvinylpyrrolidone are used.

The adhesive for poultices may, if necessary, be purified water; a humectant comprising a polyhydric alcohol such as glycerin or propylene glycol; an inorganic filler such as kaolin, bentonite, zinc white or titanium dioxide; Agent; an anti-aging agent and the like may be added.

The external patch of the present invention may optionally contain an absorption enhancer for the purpose of improving the transdermal absorbability of the drug. Examples of the absorption enhancer include isopropyl myristate, diethyl sebacate, sorbitan monolaurate, glycerin monooleate, sodium oleyl phosphate, sodium lauryl sulfate, octyl phenyl ether, octyl phenyl ether with polyethylene glycol, octyl phenyl ether, lauryl ether, and polyethylene glycol Addition lauryl ether, sorbitan monooleate, polyethylene glycol addition sorbitan monooleate, lauroyl diethanolamide, lauroyl sarcosine, oleoyl sarcosine sugar ester, lecithin, glycyrrhetin, urea, salicylic acid, calcium thioglycolate, lactic acid, lactate ester, olive oil, squalene, Lanolin, liquid paraffin, glycerin and the like.

The content of the above-mentioned absorption promoter in the pressure-sensitive adhesive layer is preferably 20% by weight or less, more preferably 0.1% by weight.
1 to 10% by weight. When the content exceeds 20% by weight, the skin patch of the obtained external patch increases, and when applied to the skin, redness and itching may occur.

The above-mentioned topical vasodilator is not particularly limited as long as it has a function of locally stimulating the skin to expand the blood vessel locally, and examples thereof include pepper extract, pepper tincture, capsaicin, and nonyl. Acid vanillylamide and the like.

When the content of the above-mentioned local vasodilator in the pressure-sensitive adhesive layer is too small, the percutaneous absorption amount of the drug per unit area is insufficient, so that a blood concentration at which a medicinal effect is exhibited cannot be obtained. If so, the skin stimulating action becomes too strong and may cause inflammation. Therefore, the content is preferably 0.01 to 10% by weight, more preferably 0.02 to 2% by weight.

The muscle relaxant is not particularly limited as long as it has a muscle relaxing effect. Examples thereof include alcuronium chloride, suxamethonium chloride, tubocurarine chloride, suxamethonium hydrochloride, tizanidine hydrochloride, chlorphenesin carbamate, and chlorzoxazone. Chlormezanone, pancuronium bromide, diazepam, dantrolene sodium, baclofen, afloqualone, methocarbamol and the like.

If the content of the muscle relaxant in the pressure-sensitive adhesive layer is too small, the percutaneous absorption per unit area of the drug is insufficient, so that a blood concentration at which a medicinal effect is exhibited cannot be obtained. Since cracks and the like are likely to occur in the agent layer,
It is preferably 0.01 to 30% by weight, more preferably 0.1 to 30% by weight.
1 to 20% by weight.

The patch for external use of the present invention can be obtained by providing a pressure-sensitive adhesive layer containing a pressure-sensitive adhesive, a drug, and, if necessary, an absorption enhancer on a suitable support. To provide the pressure-sensitive adhesive layer on the support, for example, a solvent coating method,
Conventionally known methods for producing an adhesive tape, such as a hot melt coating method and an electron beam curing emulsion coating method, can be used. Among them, a solvent coating method is particularly preferably used.

In the solvent coating method, the pressure-sensitive adhesive is dissolved in a suitable solvent, and if necessary, various additives are added and mixed. The resulting mixture is applied to the surface of the support, dried to remove the solvent, and thereby a pressure-sensitive adhesive layer having a predetermined thickness is formed on the support to prepare a patch. Further, after the above-mentioned mixed solution is once applied onto a release paper described below and dried, the obtained pressure-sensitive adhesive layer may be laminated on a support.
The release paper may be laminated until use to protect the pressure-sensitive adhesive layer. As the release paper, for example, a polyethylene terephthalate film is used.

The thickness of the pressure-sensitive adhesive layer is 30 to 1,000.
μm is preferred. When the thickness is less than 30 μm, a predetermined amount of the drug cannot be contained in the external patch of a predetermined area, and when the thickness exceeds 1,000 μm, the drug contained in the adhesive layer near the support diffuses to the skin surface. Otherwise, the drug may not be used effectively.

As the above-mentioned support, those usually used for patches are suitable, and as the material of the support,
For example, polyethylene, cellulose acetate, ethyl cellulose, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, ethylene-methyl acrylate copolymer, plasticized polyvinyl chloride, polyurethane, Examples include polyvinylidene chloride and aluminum. These materials can be used as a single-layer sheet or a laminate of two or more sheets. In addition, materials other than aluminum may be used as a woven or nonwoven fabric.

[0033]

Next, embodiments of the present invention will be described. (Example 1) 65% by mole of 2-ethylhexyl acrylate
And a monomer composition consisting of 35 mol% of vinylpyrrolidone and 0.02% by weight of hexamethylene dimethacrylate based on the monomer composition in a separable flask, and further adding ethyl acetate to give a monomer concentration of 85%. It adjusted so that it might become weight%. This solution was heated to 60 ° C. under a nitrogen atmosphere, and polymerization was carried out for 32 hours while adding an ethyl acetate solution of lauroyl peroxide as a polymerization initiator little by little to obtain an ethyl acetate solution of an acrylic pressure-sensitive adhesive. Ethyl acetate was further added to the obtained acrylic pressure-sensitive adhesive solution to adjust the solid concentration to 35% by weight.

88.5 parts by weight (in terms of solid content) of the acrylic pressure-sensitive adhesive solution, 0.5 parts by weight of pepper extract (manufactured by Nippon Powder Chemical Co., Ltd.), and 10 parts by weight of chlorphenesin carbamate (manufactured by Nippon Bulk Pharmaceutical Co., Ltd.) And 1 part by weight of lauroyl sarcosine (manufactured by Nacalai Tesque, Inc.), and further, ethyl acetate was added so as to have a solid concentration of 25% by weight, and the mixture was sufficiently stirred with a dissolver to obtain a coating liquid.

The above coating solution was coated on a 50 μm-thick polyethylene terephthalate release paper and dried in a 60 ° C. gear oven for 30 minutes to form a 100 μm-thick pressure-sensitive adhesive layer. On this adhesive layer, an ethylene-vinyl acetate copolymer side of a laminated film of polyethylene terephthalate and ethylene-vinyl acetate copolymer having a thickness of 38 μm (manufactured by Nippon Matai Co., Ltd.) was laminated to prepare an external patch. .

Example 2 Styrene-isoprene-styrene block (SIS) copolymer ("Q" manufactured by Zeon Corporation)
TC3420 ") 100 parts by weight, 33 parts by weight of polybutene (" HV-300F "manufactured by Nippon Petrochemical Co., Ltd.), alicyclic saturated hydrocarbon resin (" Alcon P-90 "manufactured by Arakawa Chemical Co., Ltd.)
283 parts by weight and liquid paraffin (manufactured by Nikko Pharmaceutical Co., Ltd.)
250 parts by weight were added to and mixed with cyclohexane to obtain a rubber-based pressure-sensitive adhesive solution having a solid concentration of 45% by weight.

Capsaicin (manufactured by Wako Pure Chemical Industries, Ltd.) was added to 86.98 parts by weight (in terms of solid content) of the rubber-based pressure-sensitive adhesive solution.
02 parts by weight, chlormezanone (Nippon Bulk Pharma Co., Ltd.) 1
0 parts by weight and 3 parts by weight of lactic acid (manufactured by Maruishi Pharmaceutical Co., Ltd.) were added, and cyclohexane was further added so as to have a solid concentration of 40% by weight, followed by sufficient stirring with a dissolver to obtain a coating solution. The coating solution was coated on release paper in the same manner as in Example 1 to form a pressure-sensitive adhesive layer, and then the pressure-sensitive adhesive layer was coated on a laminated film of polyethylene terephthalate and ethylene-vinyl acetate copolymer. -The vinyl acetate copolymer side was laminated to prepare an external patch.

Example 3 1 part by weight of sodium polyacrylate ("Aronbisua" manufactured by Nippon Pure Chemical Co., Ltd.), 8 parts by weight of aluminum silicate (manufactured by Wako Pure Chemical Industries, Ltd.), and glycerin (manufactured by Maruishi Pharmaceutical Co., Ltd.) 20 A part by weight was added and mixed and dispersed to obtain a solution (A). Separately, polyethylene glycol 40
0 (manufactured by Wako Pure Chemical Industries, Ltd.), 2 parts by weight of polysorbate 80 (manufactured by Wako Pure Chemical Industries, Ltd.), 3 parts by weight, nonylate warinylamide (SI
A solution (B) was obtained by adding 0.04 parts by weight of GMA and 0.5 parts by weight of diazepam (manufactured by Nippon Bulk Pharmaceutical Co., Ltd.) and dissolving by heating.

8 parts by weight of gelatin (manufactured by Wako Pure Chemical Industries), 0.5 parts by weight of carboxyvinyl polymer (manufactured by Wako Pure Chemical Industries)
And after adding 54.46 parts by weight of purified water to 2.5 parts by weight of sodium alginate (manufactured by Wako Pure Chemical Industries, Ltd.) and dissolving by heating,
The solution (A) was added and mixed, and the solution (B) was further added and uniformly stirred and mixed. These mixtures are added to a thickness of 100
It was spread on a non-woven fabric to a thickness of μm and covered with a polyethylene film to prepare a poultice.

Comparative Example 1 An external patch was prepared in the same manner as in Example 1 except that chlorphenesin carbamate was not added at all.

Comparative Example 2 An external patch was prepared in the same manner as in Example 2 except that chlormezanone was not added at all.

Comparative Example 3 A poultice was prepared in the same manner as in Example 3 except that no diazepam was added.

The above-mentioned external patches and cataplasms were evaluated for the following properties, and the results are shown in Table 1.

(1) Rat Skin Temperature Measurement Test An external patch was applied to the back of a shaved Wistar rat (male, 6 weeks old), covered with gauze, and fixed with tape from above. Peeled off after 12 hours from fixing,
The skin temperature of the application site before application and immediately before the application was measured using a surface temperature system, and the rise in skin temperature at the time of application was determined.

(2) Rat skin migration test In the rat skin temperature measurement test of (1), the external patch applied to the back of the rat was peeled off after 12 hours, and the residual concentration of the muscle relaxant was measured by liquid chromatography. Measured by
The transfer amount of the muscle relaxant was calculated from the difference between the initial concentration and the residual concentration of the muscle relaxant contained in the external patch.

[0046]

[Table 1]

[0047]

The topical patch of the present invention has the above-mentioned constitution, and the muscle relaxant is well percutaneously absorbed without suppressing the effect of increasing the skin temperature. In addition to the promoting effect, a high therapeutic effect on shoulder periarthritis, low back pain and the like is obtained.

Claims (2)

[Claims] 1. An external patch comprising an adhesive layer provided on one side of a support, wherein the adhesive layer contains a local vasodilator and a muscle relaxant. . 2. The external patch according to claim 1, wherein the topical vasodilator is at least one selected from pepper extract, pepper tincture, capsaicin and nonylate wanilylamide.