JPH10298065A - Plaster having warm feeling - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a plaster having warming activities, and reducing a dermal irritation caused by a nonsteroidal antiinflammatory agent, etc., by forming a specific substrate layer containing water on a supporting layer comprising a polymer film and a woven or nonwoven fabric. SOLUTION: This plaster having warm feeling is obtained by using a laminate obtained by adhering a polymer film having <=200 g/m<2> /24 hr moisture permeability to a woven or nonwoven fabric as a supporter layer, and forming a hydrophilic substrate layer containing 30-80 wt.% water on the woven or nonwoven fabric face of the supporter layer. The hydrophilic substrate is for example a polyacrylic acid, gelatin and casein. Formulation of indomethacin, ketoprofen, felbinac, etc., is preferable in view of antiinflammatory activities. The formulation of a blood flow promoter such as vitamin E acetate and sodium polyethylenesulfonate is preferable in view of increasing effects of a skin temperature.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a patch, and more particularly, to a patch having a heating effect and reduced skin irritation caused by a nonsteroidal anti-inflammatory drug.

[0002]

2. Description of the Related Art Patches can be classified into two types according to their use. One is a cold patch which is mainly used for acute inflammation (sprain, bruise, etc.), and the other is a warm patch which is effective mainly for chronic inflammation (stiff shoulder, back pain, etc.). Treatment of acute inflammation requires cooling the affected area, whereas chronic inflammation requires conversely warming to relax muscles and increase blood flow.

JP-A-7-330589, JP-A-7-330589
Japanese Patent Application Laid-Open No. 6-85882 and Japanese Patent Application Laid-Open No. 8-127531 describe a patch support having excellent anti-diffusion property of a drug. In addition, the patch containing water in the base,
The cooling sensation type is widely used for the purpose of reducing physical stimulus when peeling and increasing the cooling sensation. However, although a patch using a heat-retaining effect of water has been reported as a warming-type patch, a patch which is expected to have the same effect with a hydrophilic base is not known.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a patch having a high thermal effect and little skin irritation.

[0005]

Means for Solving the Problems The present inventors formed a water-containing base layer on the woven or nonwoven surface of a support layer in which a woven or nonwoven fabric was adhered to the surface of a polymer film having low moisture permeability. When the provided patch was manufactured, it was found that the obtained patch had a high thermal effect when applied, and the present invention was completed.

That is, according to the present invention, the moisture permeability is 200 g / m2.
A woven or non-woven surface of the support layer that bonds the ^2/24 hr or less of the polymer film and woven or nonwoven fabric, the water 30
A warming patch characterized by being provided with a hydrophilic base layer containing about 80% by weight.

[0007]

The polymer film used in the Detailed Description of the Invention The present invention has moisture permeability of less than 200g / m ² / 24hr,
100g / m ² / 24hr following are more preferred. This is because sufficient thermal effect when the moisture permeability of the polymer film is more than 200g / m ² / 24hr can not be exhibited. Although the thickness of the film affects the moisture permeability, it is 50
Those having a size of less than 0 μm are preferred, and those having a size of less than 150 μm are more preferred.

[0008] As the polymer film in the present invention,
Examples include polyethylene, polypropylene, polyester, polyamide, polyvinyl alcohol, polyvinyl chloride, polyvinylidene chloride, polyurethane, polystyrene, ethylene-vinyl acetate copolymer, polycarbonate, and hydrochloric acid rubber. In order to secure the property, a material having a followability to the skin surface is preferable, and a film of polyurethane, polytetrafluoroethylene, polyethylene terephthalate, ethylene-vinyl acetate copolymer or the like is particularly preferable. Further, the film layer may be formed of two or more resin layers depending on the purpose, but it is preferable to select a material that has heat sealing properties and can be easily heat-sealed. .

The woven or non-woven fabric in the present invention is not particularly limited as long as it is generally used for a patch, and examples of the woven fabric include flannel, cotton, silk, polyester, and nylon. The thickness of the woven or non-woven fabric can be from thin and coarse like gauze to thick one with a thickness of about 2 mm as long as it has an appropriate gap between eyes.

The hydrophilic base includes polyacrylic acid, gelatin, casein, pullulan, dextran, sodium alginate, soluble starch, carboxy starch,
Dextrin, carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, polyvinyl alcohol, polyethylene oxide, polyacrylamide, sodium polyacrylate, polyvinylpyrrolidone, carboxyvinyl polymer, polyvinylether, polymaleic acid copolymer, methoxyethylene maleic anhydride Conventionally used synthetic or semi-synthetic hydrophilic polymers such as acid copolymers, isobutylene maleic anhydride copolymers, and polyethyleneimines can be used.

The base must contain 30 to 80% by weight of water, preferably 50 to 80% by weight.
If the content is less than 30% by weight, the heat retaining effect is not sufficient, and if the content exceeds 80% by weight, the production becomes difficult.

Further, the patch of the present invention has a pH of 3.
The range of 5 to 7 is preferable, and the range of 4 to 6.5 is more preferable. If the pH is out of the range of 3.5 to 7, skin irritation occurs.

In general, patches include anthranilic acids such as fenamic acid, phenylacetic acids such as diclofenac and felbinac, indoles such as indomethacin, propionic acids such as ketoprofen and flurbuprofen, and phenylbutazone. It is preferable from the viewpoint of the anti-inflammatory effect that a non-steroidal anti-inflammatory agent such as a benzothiazine-based compound such as pyrazolone or piroxicam, or a sulfonamide-based compound such as Nimeslide is added. However, the present inventors have also found that these non-steroidal anti-inflammatory agents themselves may cause skin irritation, but when these anti-inflammatory agents are blended with the patch of the present invention, It has also been found that it has the effect of reducing the skin irritation caused, especially the unique skin irritation caused by indomethacin. The effect of reducing skin irritation is presumed to be due to an increase in skin blood flow, but the specific reason is unknown.

The amount of the non-steroidal anti-inflammatory agent to be added is preferably 0.1 to 10% by weight, more preferably 0.1 to 5% by weight in the base. In the case of a patch, the anti-inflammatory effect cannot be expected if the amount of the non-steroidal anti-inflammatory agent is less than 0.1% by weight, and if the amount exceeds 10% by weight, the skin irritates the non-steroidal anti-inflammatory agent itself. This is because there is a possibility of occurrence.

Further, according to the present invention, if a blood flow promoting agent such as vitamin E acetate, sodium polyethylenesulfonate, vanillylamide nonylate, capsicum extract, capsicum powder, capsicum tincture, capsaicin, benzyl nicotinate, or pelargonic acid is added, skin temperature may be reduced. It is preferable in terms of the ascending effect. As the blood flow promoter, vitamin E acetate, vanillyl amide nonylate, pepper extract, benzyl nicotinate or sodium polyethylenesulfonate are particularly preferred from the viewpoint of safety and efficacy.

The effect of increasing the skin temperature in the present invention is greatly affected by the blood flow promoter, so that the compounding concentration differs depending on the blood flow promoter. That is, vitamin E acetate is 0.1 to 5% by weight in the base, and nonylate vanillylamide is 0.00% by weight.
1 to 0.5% by weight, capsicum extract is 0.1 to 30% by weight as a crude drug equivalent, benzyl nicotinate is 0.0
It is preferable that 1 to 5% by weight and sodium polyethylene sulfonate be added in the range of 0.01 to 5% by weight.
If the amount is less than the above range, the effect of blending the blood flow enhancer cannot be sufficiently obtained, and if the amount exceeds the range, skin irritation of the blood flow enhancer itself may occur.

The base of the patch of the present invention may be, if necessary, a lower alcohol (methanol, ethanol, denatured ethanol, isopropyl alcohol, etc.), a solubilizer (diisopropyl adipate, isopropyl myristate, 1,3-butylene). Glycol, propylene glycol, polyethylene glycol, glycerin, medium-chain fatty acid triglycerides, fatty acid esters, various vegetable oils, various animal oils, polyhydric alcohol fatty acid esters, alkyl glyceryl ethers, hydrocarbons, lactic acid, sodium hydroxide, etc.), surfactants (Sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, propylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbit fatty acid ester Ter, polyoxyethylene glycerin fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, poly Oxyethylene beeswax derivatives, polyoxyethylene lanolin derivatives, polyoxyethylene alkylamides, polyoxyethylene alkylamines, lecithin derivatives, high molecular emulsifiers, etc., emulsion stabilizers (higher alcohols, etc.), gelling agents (high polymers, etc.), Commonly used base components such as adhesives can be blended. Depending on the purpose of use, vasodilators (carpronium chloride, assembly extract, panax ginseng extract, etc.), adrenal gland Hormone (hydrocortisone acetate, butyrate propionate hydrocortisone, etc.), keratolytics (urea, salicylic acid and the like),
Humectants (sodium hyaluronate, chondroitin sulfate, cordyceps extract, saffron extract, etc.), fungicides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, hinokitiol, etc.), antioxidants (dibutylhydroxytoluene, isopropyl) Gallate, etc.), a refreshing agent (menthol, peppermint oil, camphor and the like), a fragrance, a pigment, and the like can be blended as long as the effects of the invention are not impaired.

[0018]

According to the present invention, it has become possible to provide a patch not only having a high thermal effect but also reducing skin irritation of a nonsteroidal anti-inflammatory drug.

[0019]

The present invention will be described more specifically with reference to the following examples and test examples.

Example 1 Sodium polyacrylate 4% by weight Polyacrylic acid 8 Glycerin 6 Aluminum magnesium hydroxide 0.25 Silicic anhydride (average particle diameter: 10 mμ) 1.5 Nikkor TS-10 (trade name) 0.3 Indomethacin 0.5 Purified water 79.45 Glycerin and purified water of 70% by weight were added to sodium polyacrylate and polyacrylic acid to dissolve. Silicic anhydride was uniformly mixed with the solution while stirring with the remaining purified water. Separately, after Nikkor TS-10 and aluminum magnesium hydroxide were uniformly stirred, they were added to the above aqueous solution of polyacrylic acid and mixed to obtain a plaster body.

After the obtained plaster is spread on a polyester liner to a thickness of about 1 mm, a polyester non-woven fabric is bonded, and then a polyethylene polymer film (100 g / water permeability) is applied to the non-woven fabric using a double-sided tape. m ^2/2
4 hr). The patch was cut into a predetermined size to obtain a patch.

Example 2 A patch was obtained in the same manner as in Example 1 except that indomethacin in Example 1 was changed to ketoprofen.

Example 3 A patch was obtained in the same manner as in Example 1 except that indomethacin in Example 1 was changed to flurbiprofen.

Example 4 A patch was obtained in the same manner as in Example 1 except that indomethacin in Example 1 was changed to verbinac.

Example 5 A patch was obtained in the same manner as in Example 1 except that indomethacin in Example 1 was changed to flurbiprofen.

Example 6 A patch was obtained in the same manner as in Example 1 except that indomethacin in Example 1 was changed to piroxicam.

Example 7 Sodium polyacrylate 4% by weight Polyacrylic acid 8 Glycerin 6 Aluminum magnesium hydroxide 0.25 Silicic anhydride (average particle size: 10 mμ) 1.5 Nikkor TS-10 0.3 Diphenhydramine 0.1 Nonylate vanillylamide 0.005 Benzyl nicotinate 0.125 Indomethacin 0.5 Purified water 79.22 A patch was produced according to the above formulation and according to Example 1.

Example 9 An adhesive plaster was manufactured according to the formulation of Example 1, and the adhesive plaster was spread on a polyester liner to a thickness of about 1 mm, and a polyester nonwoven fabric was laminated. Urethane polymer film (150g /
pasted m ² / 24hr). The patch was cut into a predetermined size to obtain a patch.

Example 10 A plaster was prepared according to the formulation of Example 1, and the plaster was spread on a polyester liner to a thickness of about 1 mm, and then a polyester nonwoven fabric was laminated. Polypropylene polymer film (moisture permeability 50)
g / m ² / 24hr) was adhered to. The patch was cut into a predetermined size to obtain a patch.

Comparative Example 1 An adhesive plaster was prepared according to the formulation of Example 1, and the adhesive plaster was spread on a polyester liner to a thickness of about 1 mm, and then a polyester nonwoven fabric was laminated. The patch was cut into a predetermined size to obtain a patch.

COMPARATIVE EXAMPLE 2 A plaster was prepared in the same manner as in Example 1 except that indomethacin was removed, and the plaster was spread on a polyester liner to a thickness of about 1 mm, and a polyester nonwoven fabric was laminated. . Thereafter, the patch was cut into a predetermined size to obtain a patch.

Comparative Example 3 An adhesive plaster was prepared according to the formulation of Example 7, and the adhesive plaster was spread on a polyester liner to a thickness of about 1 mm, and a polyester nonwoven fabric was laminated. Thereafter, the patch was cut into a predetermined size to obtain a patch.

Test Example 1 The patches obtained in Example 1 and Comparative Examples 1 and 2 were closed and applied to six subjects for 24 hours. Twenty-four hours later, the patch was peeled off, and the skin irritation was visually determined, and the value was taken as the immediately after value. After 1 hour, 3 hours, 5 hours, and 24 hours, the same determination was made. Table 1 shows the results of visual evaluation, in which no response was scored as 0, faint erythema was 1, and clear erythema was 2.

[0034]

[Table 1]

As is evident from Table 1, Example 1 clearly reduced the skin irritation of indomethacin, which was almost the same as Comparative Example 2 in which indomethacin was not added.

Test Example 2 An efficacy questionnaire test was conducted on the preparations obtained in Example 7 and Comparative Example 3 for 10 patients complaining of stiff shoulders. It was instructed to apply an appropriate amount to the affected area several times a day as the dosage and administration. At the end of application, the degree of improvement in stiff shoulder symptoms as compared to the start was markedly improved, moderately improved,
Evaluation was made on a five-point scale of "slight improvement", "unchanged", and "deterioration". The results are shown in Table 2.

[0037]

[Table 2]

Test Example 3 The preparations obtained in Example 7 and Comparative Example 3 were subjected to a sticking test to rats, and the transition of indomethacin blood concentration was measured. The application method is 30cm abdomen after fixing the rat in the dorsal position.
^The blood was collected from the cervical artery over time. The quantification was performed using the HPLC method. At this time, the limit of quantification was 50 ng / ml. Table 3 shows the results.

[0039]

[Table 3]

Test Example 4 With respect to the preparations obtained in Example 7 and Comparative Example 3, a patch cut into a size of 14 × 10 cm was administered to the back of 10 male subjects, and changes in skin temperature over time were thermographed (Nihon Kohden). It measured using. The subject entered a room maintained at a constant temperature and humidity (temperature of 23 ° C., relative humidity of 60%) in order to keep the skin temperature constant, then undressed his upper body and waited. One hour after the subject undressed, it was confirmed that the skin temperature was constant in the room, and the measurement was started. The results are shown in Table 4 as average values of skin temperature change (° C.) from the beginning.

[0041]

[Table 4]

Claims (6)

[Claims] To 1. A woven or nonwoven fabric surface of the support layer moisture permeability was bonded to the following polymer films and woven or nonwoven 200g / m ² / 24hr, hydrophilic containing 30 to 80 wt% of water A warming patch comprising a base layer. 2. The method according to claim 1, wherein the base layer comprises vitamin E acetate, sodium polyethylene sulfonate, vanillyl amide nonylate,
Pepper extract, pepper powder, pepper tincture,
The patch according to claim 1, further comprising at least one blood flow enhancer selected from capsaicin, benzyl nicotinate, and pelargonic acid. 3. The patch according to claim 1, wherein a non-steroidal anti-inflammatory agent is blended in the base layer. 4. The nonsteroidal anti-inflammatory agent is an anthranilic acid type, a phenylacetic acid type, an indole type, a propionic acid type,
The patch according to claim 3, which is at least one member selected from pyrazolones, benzothiazines, and sulfonamides. 5. The patch according to claim 3, wherein the nonsteroidal anti-inflammatory drug is at least one selected from indomethacin, ketoprofen, felbinac, piroxicam and flurbiprofen. 6. The patch according to claim 1, wherein the pH of the base is in the range of 3.5 to 7.