JPH05208907A - Antiinflammatory and analgesic cataplasm - Google Patents

Abstract

PURPOSE:To provide the subject cataplasm good in stability, excellent in the pharmacodynamic manifestivity, also giving low irritancy and low odor. CONSTITUTION:The objective cataplasm can be obtained by bearing (A) a plaster layer comprising a medicinal substance containing 0.5-7wt.% of L- menthol, 1.0-12wt.% of glycol salicylate, 0.005-0.5wt.% of nonylic vanillylamide, and 0.1-5.0wt.% of glycryrrhetinic acid, each based on the plaster layer, and (2) a tacky agent of a rubber-based one, on (B) one side of a substrate.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is a hypoallergenic composition comprising a plaster layer containing L-menthol, glycol salicylate, nonyl vanillyl amide and glycyrrhetinic acid and a rubber adhesive on one side of a support. The present invention relates to a low-odor anti-inflammatory analgesic patch.

[0002]

BACKGROUND OF THE INVENTION Conventionally, as an anti-inflammatory analgesic external preparation for the purpose of healing stiff shoulders, low back pain, muscle pain, muscle fatigue, etc.,
JP-B-61-39929, JP-A-54-138124
No. 60-34922, JP-A-56-3901
4, as disclosed in JP-A-63-255219, methyl salicylate, glycol salicylate, L-
Those containing anti-inflammatory and analgesic agents such as menthol and (DL-, L-) camphor are widely used.

It is known that diphenhydramines and other antihistamines, vitamin E and the like are additionally incorporated in order to more effectively develop the anti-inflammatory and analgesic effect of such drugs.

Further, JP-A-60-188315 proposes an antipruritic plaster containing glycyrrhetinic acids.

[0005]

However, in the conventional patch as described above, some people may feel severe irritation on the skin, and some products have a strong odor. It wasn't all.

The present invention has been made in view of the above circumstances, and an object thereof is to provide an anti-inflammatory analgesic patch in which both irritation and odor to the skin are weakened as much as possible.

[0007]

The present invention has been devised to achieve the above object, and is a hypoallergenic and odorless anti-inflammatory analgesic patch by combining specific drug components in a specific ratio. It was completed with the knowledge that a drug can be obtained.

That is, the anti-inflammatory / analgesic patch according to the present invention is a patch having a plaster layer containing a drug and an adhesive on one side of a support, wherein L-menthol is 0.5 ~ 7 wt%, glycol salicylate 1.0-12 wt%, nonyl vanillyl amide 0.0
05-0.5 wt% and glycyrrhetinic acid 0.1-
It is contained at a concentration of 5.0 wt% in the plaster layer, and the adhesive is a rubber-based adhesive.

The respective components and manufacturing method of the patch according to the present invention will be described in detail below.

A) Drug Among the drugs of the anti-inflammatory analgesic patch according to the present invention, first, L-menthol has the structural formula

[0011]

[Chemical 1]

It is a substance that has a wide range in nature.
It gives a refreshing refreshing sensation and has analgesic and antipruritic effects.

This is contained in the plaster layer in the range of 0.5 to 7% by weight. If the L-menthol content is too low, the effects of analgesia and astringency are low, and if it is too high, the menthol odor is too strong. A particularly suitable range for the content of L-menthol is 0.5 to 5% by weight.

Glycol salicylate has the structural formula

[0015]

[Chemical 2]

Is a substance having It exhibits anti-inflammatory and analgesic effects.

Glycol salicylate is 1.0 in the plaster layer.
It is contained in the range of up to 12% by weight. When the content of glycol salicylate is too small, the anti-inflammatory and analgesic effect is low, and even when the content is excessive, the anti-inflammatory and analgesic effect cannot be expected so much. A particularly preferable range of the content of glycol salicylate is 2 to 10% by weight.

Nonyl acid vanillyl amide has the structural formula

[0019]

[Chemical 3]

Is a substance having It exhibits a vasodilatory effect.

Nonyl acid vanillyl amide was added to the plaster layer in an amount of 0.
It is contained in the range of 005 to 0.5% by weight. If the content of nonyl acid vanillyl amide is too small, the vasodilating effect is low, and if it is too large, the feeling of heat becomes too strong. A particularly preferred range of the content of nonyl vanillyl amide is 0.005
It is 0.3% by weight.

Glycyrrhetinic acid has the structural formula

[0023]

[Chemical 4]

Is a substance having This is a hydrolysis product of glycyrrhizin (glycyrrhizic acid) which is a licorice extract component. It exhibits mild anti-inflammatory and anti-allergic effects on the dominant eye, and serves to suppress irritation.

Glycyrrhetinic acid is added to the plaster layer in an amount of 0.1-0.1%.
It is contained in the range of 5.0% by weight. If the content of glycyrrhetinic acid is too small, the anti-inflammatory effect is low, and if it is too large, it becomes difficult to dissolve it uniformly in the plaster. A particularly suitable range of the content of glycyrrhetinic acid is 0.1 to 3% by weight.

B) Rubber Adhesive The rubber adhesive of the anti-inflammatory analgesic patch according to the present invention is mainly composed of a rubber adhesive component, a tackifying component, a softening agent, an antioxidant and a preservative. As a rubber-based adhesive component, natural rubber, styrene-butadiene copolymer,
Examples thereof include synthetic rubbers such as styrene-isoprene-styrene copolymer elastomer, silicone rubber, polyisoprene, polyisobutylene, ethylene-vinyl acetate copolymer. Examples of the tackifying component include rosin-based resins (rosin, hydrogenated rosin, esters thereof, etc.), polyterpene resins, coumarone-indene resins, petroleum-based resins (aliphatic and alicyclic resins), terpene-phenolic resins, etc. Is exemplified. Examples of the softening agent include polybutene, liquid paraffin, higher fatty acid esters (such as isopropyl myristate), silicone, and vegetable oil. Examples of the antioxidant include butylhydroxyanisole, guaiacol esters, dibutylhydroxytoluene, nordihydroguaiaretic acid and the like. Examples of preservatives include thymol.

The content of the rubber-based adhesive component is preferably in the range of 10 to 50% by weight based on the total amount of the paste. The tackifying component and the softening agent are appropriately selected in consideration of the amount of the rubber-based adhesive component used, and the content of each of these components is preferably in the range of 5 to 50% by weight based on the total amount of the paste. The total content of each of the rubber-based adhesive component, the tackifying component and the softening agent is preferably 70% by weight or more based on the total amount of the paste.

C) Support As a support of the present patch, a support that is flexible but has a function of giving self-supporting property to the patch and preventing volatilization and migration of the drug in the plaster layer is used. To be done. Materials for the support include cellulose acetate, ethyl cellulose, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyvinyl chloride, urethane copolymer. , Polyurethane, polyethylene, polyvinylidene chloride, aluminum and the like. These materials are used, for example, as a single layer sheet or film or a laminate of two or more sheets. Materials other than aluminum may be used as woven or non-woven fabrics. As the support, a support made of a material having conformability to the skin surface is preferably used, and a polyvinyl chloride film and a laminate film of a polyethylene terephthalate film and an ethylene-vinyl acetate copolymer film are particularly preferable. The thickness of the support is preferably 5 to 2000 μm.

Further, in order to improve the adhesion between the support and the plaster layer, the support may be subjected to corona treatment, plasma discharge treatment, or an anchor coating agent may be applied.

D) Release paper The patch is usually provided with a release paper on its surface for protecting the plaster layer surface until use. As the release paper, those obtained by subjecting a polyethylene terephthalate film to silicon treatment and high-quality paper are often used, but they are not limited. The thickness of the release paper is preferably 5 to 200 μm.

E) Manufacturing method As a method for manufacturing the patch according to the present invention, a general method for manufacturing an adhesive tape can be applied. Examples thereof include a hot melt coating method, a solvent coating method, and an electron beam curing emulsion coating method.

To manufacture the patch according to the present invention by the hot melt coating method, for example, the following operation is performed. A predetermined amount of constituent components of the rubber-based pressure-sensitive adhesive is mixed, and the mixture is heated and stirred at a temperature of 120 to 170 ° C under nitrogen substitution to melt. Then,
The temperature of the pressure-sensitive adhesive melt is lowered to 50 to 150 ° C., a drug is added to this and the mixture is uniformly mixed to obtain a plaster.

Next, the molten plaster is spread on a release paper (about 5 to 200 μm) by a hot melt coater and a support (about 5 to 2000 μm) is adhered onto it, or the plaster described above. Is spread on a support, and release paper is brought into close contact therewith. The obtained patch original fabric is
It is processed into an appropriate shape in consideration of the various symptoms.

The thickness of the plaster layer after drying varies depending on the purpose of use, but is usually in the range of 30 to 500 μm. If this thickness is less than 30 μm, the required amount of drug cannot be contained and the adhesiveness is insufficient. If the thickness exceeds 500 μm, the drug contained in the plaster layer near the support does not sufficiently diffuse, and the drug release property decreases.

[0035]

EFFECTS OF THE INVENTION The anti-inflammatory and analgesic patch of the present invention comprises L-menthol, glycol salicylate, nonyl acid vanillyl amide, and glycyrrhetinic acid as drugs, and these are blended in the required proportions. It is possible to obtain an anti-inflammatory analgesic patch that is excellent in the manifestation of medicinal effects, is mild, and has a low odor.

Further, since all the drugs used in the present invention have good thermal stability, the anti-inflammatory analgesic patch of the present invention can be produced by the hot melt coating method, and thus the production is also simple.

[0037]

EXAMPLES Next, in order to specifically describe the present invention, some examples showing one example of the present invention and some comparative examples showing a comparison therewith are given, and the performance test of each obtained patch is further given. The results are shown.

Example 1 The three types of pressure-sensitive adhesives (SIS, Alcon and liquid paraffin) shown in Table 1 below were mixed, and the temperature was changed to about 15 under nitrogen substitution.
It was melted by stirring with heating at 0 ° C. Then, the temperature of the adhesive melt was lowered to about 100 ° C., and four kinds of drugs (L-menthol, glycol salicylate, vanillyl amide nonylate and glycyrrhetinic acid) in Table 1 below were added thereto.
Was added in the proportions shown in Table 1 and mixed uniformly while heating to obtain a plaster.

Next, the melted paste was spread on a release paper (thickness: about 105 μm) made of polyethylene-coated high-quality paper with a hot-melt coater, and a support made of a polyvinyl chloride film (thickness: about 70 μm) was formed on the release paper. ) Was made to adhere. The thickness of the plaster layer after drying was about 90 μm. The obtained patch original fabric was processed into a square (2.54 cm x
2.54 cm).

Example 2, Comparative Examples 1-2 As shown in Table 1, the adhesive and the composition of the drug and the compounding ratio were changed, and the patch was obtained by the same operation as in Example 1.

[0041]

[Table 1]

In Table 1, SIS: styrene-isoprene-styrene block copolymer [Califlex TR1107, Shell Chemical Co., Ltd.
Alicyclo Saturated Hydrocarbon Resin: [Alcon P90, Arakawa Chemical Co., Ltd., softening point 90 ° C.] Liquid paraffin [Wako Pure Chemical Industries, Ltd.] Hydrogenated rosin ester: [Ester gum H Arakawa Chemical Co., Ltd.] In addition, peppermint oil was added as a perfume ingredient.

[Beta] -Butoxyethyl nicotinate is a drug having a vasodilatory effect.

Performance Test Performance tests were conducted on the patches obtained in Examples and Comparative Examples by the following method.

<Stability Test> Examples 1 and 2, Comparative Example 1,
Immediately after producing each patch of 2
It was placed in an incubator for 2 weeks and stored for 2 weeks. After that, the content of each drug in the patch is quantified, and the content of the drug charged at the time of production is 100
The relative residual ratio (%) was calculated as%.

The amounts of L-menthol, glycol salicylate and camphor were determined by gas chromatograph using the internal standard method after extracting each formulation with n-butyl acetate. Nonyl acid vanillyl amide was quantified using acetonitrile / water / phosphoric acid = 55/45 / 0.05 for each formulation.
Extraction treatment was carried out with a mixed liquid consisting of (weight ratio), and this mixed liquid was subjected to liquid chromatography using the internal standard method as a mobile phase. Glycyrrhetinic acid was quantified by subjecting each preparation to extraction treatment with a phosphoric acid / acetone mixed solution, and then performing liquid chromatography using an internal standard method. Vitamin E acetate and -β-butoxyethyl nicotinate were quantified by subjecting each formulation to extraction treatment with a cyclohexane / methanol mixture, and by liquid chromatography using an absolute calibration curve method.

<Paste Test> Examples 1 and 2, Comparative Examples 1 and 2
Each patch (2.54 × 2.54 cm) was subjected to a patch test on human skin as described below. That is,
The patch was applied to the shoulders of 10 (normal, male) test subjects. After applying for 8 hours, 3 for pharmacological effect, aromatic and irritating
For each item, each patch was evaluated on a three-point scale.

The results of the stability test and the sticking test are shown in Table 2 below.

[0049]

[Table 2]

The evaluation criteria of the sticking test are as follows.

Pharmacological effect ○: Stiff shoulder reduced, △: stiff shoulder slightly reduced, ×: unchanged Aroma ○: favorable, △: neither, ×: unpleasant irritation −: no reaction, ±: mild Erythema, +: causes erythema

Since β-butoxymethyl nicotinate is a substance having poor thermal stability, it mainly disappears during hot melt coating.

As is clear from Table 2, L-as a drug
By selecting menthol, glycol salicylate, nonyl acid vanillyl amide, and glycyrrhetinic acid, and mixing them in the required ratios, a stable, low-irritant, low-odor anti-inflammatory analgesic patch can be obtained by removing camphor. be able to.

Continuation of the front page (51) Int.Cl. ⁵ Identification code Reference number within the agency FI Technical display location A61K 31/56 7252-4C 31/60 AAH 7252-4C // (A61K 31/045 31:60 7252-4C 31 : 165 8413-4C 31:56) 7252-4C (72) Inventor Yukio Yamaguchi 4-12-2-506 Minamiosawa, Hachioji City, Tokyo (72) Inventor Masaharu Asai 764-5401 Minamiootsuka, Kawagoe City, Saitama Prefecture (72) Inventor Nobuyuki Tokuse 233-105 Kamihirama, Nakahara-ku, Kawasaki City, Kanagawa Prefecture

Claims (1)

[Claims] 1. A patch having a plaster layer containing a drug and an adhesive on one surface of a support, wherein the drug is 0.5 to 7% by weight of L-menthol and 1% of glycol salicylate. 0.0-12% by weight, vanillylamide nonylate in an amount of 0.005-0.5% by weight, and glycyrrhetinic acid in a concentration in the plaster layer of 0.1-5.0% by weight, and the adhesive is a rubber-based adhesive. An anti-inflammatory analgesic patch characterized by being an adhesive.