JP2008179564A - Anti-inflammatory and analgesic plaster - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an anti-inflammatory and analgesic plaster having excellent skin permeability of felbinac and a good feeling of effects by moderate thermal sensation stimulation, without using a rosin-based resin, crotamiton and 1-menthol acting as a skin sensitizing ingredient or a skin irritating ingredient. <P>SOLUTION: The anti-inflammatory and analgesic plaster is provided with a pressure-sensitive adhesive layer containing the felbinac and formed on one surface of a support. In the anti-inflammatory and analgesic plaster, the pressure-sensitive adhesive layer comprises (a) a styrene-isoprene-styrene block copolymer, (b) a terpenic resin, (c) a plasticizer, (d) an antioxidant, (e) the felbinac and (f) at least one kind of thermal sensation stimulating ingredient selected from the group consisting of nonylic acid vanillylamide and capsaicin. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an anti-inflammatory analgesic patch in which a pressure-sensitive adhesive layer containing felbinac, which is a kind of non-steroidal anti-inflammatory analgesic, is provided on one side of a support. The anti-inflammatory analgesic patch of the present invention can administer felbinac percutaneously to the local tissue with good skin permeability, and give the patient unpleasantness by imparting moderate warmth irritation. It is possible to demonstrate a sense of effectiveness.

  Felbinac is a kind of phenylacetic acid derivative and is a non-steroidal anti-inflammatory analgesic having a 4-biphenylacetic acid structure. Felbinac is a drug that exhibits a strong anti-inflammatory analgesic effect and has skin permeability, so it is used as a transdermal preparation such as a patch, a poultice, a plaster, a gel, or a lotion.

  A transdermal absorption patch generally has a structure in which a pressure-sensitive adhesive layer made of a pressure-sensitive adhesive composition containing a drug in a pressure-sensitive adhesive component is provided on one side of a support. In anti-inflammatory analgesic patches, drugs such as non-steroidal anti-inflammatory analgesics are required to have skin permeability. The skin has a stratum corneum in the outermost layer. This stratum corneum prevents entry of foreign substances from the outside by a chemical barrier function or the like. Therefore, many drugs are difficult to penetrate the skin.

  Conventionally, solubilizing agents such as crotamiton; fatty acids, fatty acid esters, monoterpenes, lower alcohols, polyhydric alcohols, pyrrolidones, aprotic solvents, etc., have been used to enhance the skin permeability of non-steroidal anti-inflammatory analgesics such as felbinac. Skin absorption enhancer: 1-menthol and the like are added. However, solubilizing agents such as crotamiton, transdermal absorption enhancers, 1-menthol and the like have a problem of showing skin irritation and discomfort.

  Drugs such as non-steroidal anti-inflammatory analgesics have medicinal effects such as anti-inflammatory and analgesic effects, but there is no irritation to feel their effects. Therefore, in many transdermal non-steroidal anti-inflammatory analgesic patches, 1-menthol, DL-menthol, DL-camphor, mint oil, capsaicin, Ingredients with stimulating effects such as pepper extract and nonylic acid vanillylamide are added to create a stimulating feeling that feels effective.

  A cold sensation stimulating component that develops a cooling sensation stimulating effect, such as 1-menthol, DL-menthol, DL-camphor, and peppermint oil, has a unique smell that makes it feel refreshed, and many patients dislike it.

  Warm-stimulating ingredients that produce a warming-stimulating effect such as capsaicin, red pepper extract, nonylic acid vanillylamide, etc. have almost no smell, but if there is too much content, the feeling of irritation and pain will become strong, and some patients can not stand In some cases, the anti-inflammatory analgesic patch had to be removed.

  On the other hand, if the content of the warm sensation stimulating component is too small, the sensation of sensation does not appear and the effectiveness is weakened. Furthermore, because the method of feeling the effect of the warm sensation stimulus component varies greatly among individuals, setting a content that produces an appropriate effect on the basis of the average individual causes strong pain for some patients. I felt it.

  Non-steroidal anti-inflammatory analgesic patches mainly use a combination of a rubber adhesive and a tackifier resin (tackifier) as an adhesive. When the solubility of the warming stimulus component in the tackifier resin is high, the release of the warming stimulus component is lowered, and the effectiveness of the warming stimulus is weakened. Therefore, the content of the warming sensation stimulating component must be increased, but when the content of the warming sensation stimulating component such as pepper extract or nonylic acid vanillylamide is increased, the sensation of irritation and pain become stronger.

  In anti-inflammatory analgesic patches, rosin resins used as tackifying resins are known to act as skin feel preparations. Skin sensitization is a type of delayed hypersensitivity reaction, and refers to a phenomenon in which an excessive immune reaction is caused by a chemical substance, causing skin irritation.

  In the anti-inflammatory analgesic patch, the skin layer of felbinac is improved without containing rosin resin, crotamiton, 1-menthol, etc. showing skin sensitization or skin irritation in the adhesive layer, and moderate It is desirable to reduce the content of the warm sensation stimulating component while maintaining the effectiveness.

  Japanese Laid-Open Patent Publication No. 4-321624 (Patent Document 1) proposes a felbinac-containing patch having an adhesive layer containing crotamiton, which is excellent in dissolving ability for felbinac, as an essential component. However, crotamiton tends to bleed out on the surface of the pressure-sensitive adhesive layer, and the adhesive force decreases with time. Moreover, as described in “Contact Dermatitis (1992), 27, p59” (Non-patent Document 1), crotamiton is known to have skin irritation.

  JP-A-2003-286162 (Patent Document 2) discloses a pressure-sensitive adhesive composition containing styrene-isoprene-styrene block copolymer, rosin resin, plasticizer, 1-menthol, and felbinac without using crotamiton. By forming a pressure-sensitive adhesive layer using a product, a patch that is uniformly dispersed in the pressure-sensitive adhesive layer in a semi-molten state in which a melted state of felbinac and a fine crystalline state coexist is obtained. Proposed.

  International Publication No. 98/24423 (Patent Document 3) contains styrene-isoprene-styrene block copolymer, rosin resin, plasticizer, and felbinac without using crotamiton, which is a solubilizing agent for felbinac. A patch in which an adhesive layer is formed has been proposed. In JP-A-2001-39864 (Patent Document 4), an adhesive layer in which an adhesive layer containing a styrene-isoprene-styrene block copolymer, polyisobutylene, rosin resin, plasticizer, felbinac, and a dispersant is formed. Agents have been proposed.

  However, although these patches do not contain crotamiton, they contain a rosin-based resin as an essential component, and in some cases also contain 1-menthol. However, as described in “Contact Dermatitis (1995), 33 p396-400” (Non-patent Document 2), it is known that the rosin-based resin acts as a skin sensitization component, so its inclusion is undesirable. ing. Further, as described in “Arch Dermatol (1978) vol. 114, p286” (Non-patent Document 3), 1-menthol is known to have skin irritation. Therefore, patches containing these rosin resins and 1-menthol have problems in terms of skin sensitization and skin irritation.

  JP-A-54-138124 (Patent Document 5) proposes that nonyl acid vanillylamide or capsaicin is contained in the adhesive layer of the patch as a warming stimulant. However, the content is relatively high, 0.05 to 20% by weight, and the patient may feel pain.

JP-A-4-321624 JP 2003-286162 A International Publication No. 98/24423 Pamphlet JP 2001-39864 A JP 54-138124 A Contact dermatitis: 1992; 27 p59 “Contact dermatitis from crotamiton” Contact Dermatitis: 1995; 33 p396-400 `` Rosin (colophony) and zinc oxide in adhesive bandages.An appropriate combination for rosin-sensitive patients '' Arch Dermatol: 1978, vol. 114 (Feb) p286 `` Menthol and dermatitis ''

  An object of the present invention is to provide an anti-inflammatory analgesic patch provided with a pressure-sensitive adhesive layer containing felbinac without using rosin resin, crotamiton, and 1-menthol that act as a skin irritating component or a skin irritant component. It is an object of the present invention to provide an anti-inflammatory analgesic patch which is excellent in skin permeability and has a good effect of feeling by moderate warm feeling stimulation.

  As a result of diligent research to solve the above problems, the present inventors have found that in an anti-inflammatory analgesic patch in which a pressure-sensitive adhesive layer containing felbinac is provided on one side of a support, styrene- It has been found that by using an isoprene-styrene block copolymer and selecting and using a terpene resin as a tackifier resin, a high skin permeability of felbinac can be ensured. When a terpene-based resin is used as the tackifier resin, it is possible to give a feeling of effectiveness due to a moderate warming stimulus compared to the conventional blending amount. Therefore, it is possible to suppress an excessive sense of warmth irritation due to individual differences among patients and differences in sweating.

  Since the terpene resin has a structure that does not have a polar functional group, it has low drug solubility. Therefore, when a terpene resin is included in the adhesive layer of the anti-inflammatory analgesic patch of the present invention, the skin permeability of felbinac increases, and even if the content of nonylic acid vanillylamide or capsaicin is reduced, a moderate temperature is achieved. Sensitiveness can be obtained.

  Moreover, since the anti-inflammatory analgesic patch of the present invention does not contain a general-purpose additive component that also acts as a skin irritant component such as rosin resin, crotamiton, 1-menthol, etc., skin sensitization, skin Undesirable phenomena such as irritation and strong odor can be suppressed.

Thus, according to the present invention, in the anti-inflammatory analgesic patch in which the adhesive layer containing felbinac is provided on one side of the support, the adhesive layer comprises:
(A) styrene-isoprene-styrene block copolymer,
(B) terpene resin,
(C) a plasticizer,
(D) an antioxidant,
An anti-inflammatory analgesic patch comprising (e) felbinac and (f) at least one warming sensation component selected from the group consisting of nonylic acid vanillylamide and capsaicin is provided.

According to the present invention, the following embodiments are provided.
1. The anti-inflammatory analgesic patch, wherein the adhesive layer does not contain rosin resin, crotamiton, and 1-menthol.

2. The anti-inflammatory analgesic patch, wherein the pressure-sensitive adhesive layer contains nonyl acid vanillylamide in a proportion of 0.005% by mass or less based on all components constituting the pressure-sensitive adhesive layer.

3. The anti-inflammatory analgesic patch, wherein the pressure-sensitive adhesive layer contains capsaicin at a ratio of 0.01% by mass or less based on all components constituting the pressure-sensitive adhesive layer.

  The anti-inflammatory analgesic patch of the present invention in which an adhesive layer containing ferbinac, which is a nonsteroidal anti-inflammatory analgesic, is provided on one side of the support, the adhesive layer contains rosin resin, crotamiton, and 1-menthol. Even if not, high skin permeability can be realized by the terpene resin. In addition, terpene resins with low drug solubility improve drug release and can reduce the content of nonylic acid vanillylamide and capsaicin, which are stimulant sensation-expressing substances. It is possible to suppress the difference in the feeling of the effect caused by the difference in the sweating state as much as possible.

  The content of felbinac as a medicinal component is not particularly limited, but is preferably 0.3 to 10% by mass, more preferably 0.5 to 5% by mass, based on all components constituting the pressure-sensitive adhesive layer. %.

  The styrene-isoprene-styrene block copolymer has a role of imparting tackiness to the pressure-sensitive adhesive layer, holding each component in the pressure-sensitive adhesive layer, and dissolving or dispersing other components. The content of the styrene-isoprene-styrene block copolymer is preferably 10 to 40% by mass, more preferably 20 to 35% by mass from the viewpoints of tackiness, retention of other components, dispersibility of felbinac, and the like. is there.

  If the content of the styrene-isoprene-styrene block copolymer is too small, the cohesiveness and shape retention of the pressure-sensitive adhesive layer tend to decrease. On the other hand, if the content of styrene-isoprene-styrene block copolymer is too large, the adhesive strength decreases, the components in the adhesive layer become non-uniform, or the mixing operation of each component and the application of the adhesive composition It becomes easy to cause workability reduction in work.

  The terpene resin used as a tackifying resin in the present invention has a structure that does not have a polar functional group, and the solubility of a drug having a polar group is low. Conventionally, in percutaneous absorption of a drug, it has been considered that the percutaneous absorption is better when the drug exists in a dissolved state than when the drug exists in a solid or crystalline state. It was. However, it has been found that when all of the drug is present in the pressure-sensitive adhesive layer in a dissolved state, the release of the drug is reduced, and the amount of activity that actually permeates the skin may be reduced.

  When a terpene resin is used as a tackifier resin, the solubility of felbinac in the terpene resin is low, and the dissolved felvinac and the microcrystalline state coexist in the pressure-sensitive adhesive layer. It has been found that since the fine crystalline felbinac dissolves as it penetrates the skin, the release of felbinac increases and the sustainability of medicinal effects also improves. Therefore, the anti-inflammatory analgesic patch of the present invention has a high amount of felbinac and exhibits good skin permeability over a long period of time. The content of the terpene resin is preferably 5 to 35% by mass, more preferably 10 to 25% by mass, based on all components constituting the pressure-sensitive adhesive layer.

  If the content of the terpene resin is too small, sufficient adhesive strength that enables long-time sticking cannot be obtained. On the other hand, if the content of the terpene resin is too large, the release of the drug may be reduced or peeled off. Tend to cause skin irritation.

  The plasticizer used in the present invention does not act as a drug absorption accelerator, but plays a role of softening the pressure-sensitive adhesive. Examples of the plasticizer include liquid rubbers such as high-cis polyisoprene rubber, polybutene, and polyisobutylene; petroleum-based softeners such as process oil, extender oil, and liquid paraffin.

  The plasticizers can be used alone or in combination of two or more. Content of a plasticizer is mix | blended suitably considering the shape retention of an adhesive layer, the viscosity of an adhesive composition, etc. The content of the plasticizer is preferably 10 to 60% by mass, more preferably 30 to 55% by mass, based on all components constituting the pressure-sensitive adhesive layer.

  Examples of the antioxidant used in the present invention include phenolic antioxidants BHT (chemical name: dibutylhydroxytoluene) and BHA (dibutylhydroxyanisole). The content of the antioxidant is preferably 0.1 to 2% by mass, and more preferably 0.3 to 1% by mass, based on all components constituting the pressure-sensitive adhesive layer.

  Nonylic acid vanillylamide is used for the purpose of giving warmth irritation in poultices, plasters, gels, creams, ointments, etc., but there are large individual differences in the sense of warmth irritation and almost the same concentration There may be patients who do not feel irritation and patients who feel pain because the irritation is too strong, more people who do not feel irritation with a small amount, and more people who feel irritation with a large amount Setting the amount is difficult. Even in the case of patches based on adhesives using rosin resins of the prior art, there are similar problems, and some people are somewhat stronger to give some degree of irritation common to many patients The current situation is that you can't stop feeling. In the present invention, this problem can be solved by using a terpene resin as the tackifier resin. In other words, the amount of nonylic acid vanillylamide that is less than when rosin resin is used can give an average moderate effect to multiple patients, while suppressing variations in individual differences and reducing the effect. It is possible to reduce the number of people who feel uncomfortable due to the strong effect.

  The same applies when capsaicin is used as the warming stimulus component. As described above, in Japanese Patent Laid-Open No. 54-138124 (Patent Document 5), the content of the warming stimulating component is described as 0.05 to 20% by weight in the pressure-sensitive adhesive, but in the present invention, nonyl is used. The content of acid vanillylamide can be lowered to 0.005% by mass or less, preferably 0.001 to 0.005% by mass, based on all components constituting the pressure-sensitive adhesive layer. The content of capsaicin can be 0.01% by mass or less, and further 0.0005 to 0.01% by mass.

  If the content of nonylic acid vanillylamide or capsaicin is too small, the feeling of irritation becomes difficult to develop and the effectiveness is weakened. If the content of nonylic acid vanillylamide or capsaicin is too high, irritation and pain will become strong, and some patients may not be able to tolerate and may have to remove the patch.

  One of the important features of the present invention is that the pressure-sensitive adhesive layer does not contain a rosin resin, crotamiton, and 1-menthol that act as a skin sensitizing component or a skin irritation component. The term “not containing” these components means that they are not substantially contained, and the term “substantially” means a content that causes skin sensitization or a content that has an effect as a skin irritation component. Means no. Usually, it is 3% by mass or less, preferably 1% by mass or less, more preferably 0% by mass for rosin resin, and 0.5% by mass or less, preferably 0.1% by mass or less, more preferably for crotamiton. 0% by mass. In 1-menthol, it is 0.005 mass% or less, Preferably it is 0 mass%.

  The pressure-sensitive adhesive layer of the anti-inflammatory analgesic patch of the present invention can be produced by a calendar method, a hot melt method, or the like, which is a general method for producing an anti-inflammatory analgesic patch.

  In the calendar method, first, a styrene-isoprene-styrene block copolymer, a terpene resin, an antioxidant and felbinac are kneaded at 100 to 150 ° C. for 10 to 30 minutes with a pressure kneader, and then the plasticizer is several times. And then kneading is continued. Finally, nonyl acid vanillylamide is added and further kneaded for 5 to 20 minutes to obtain a pressure-sensitive adhesive composition in which each component is uniform. The temperature and time during the kneading are described by way of examples, and are not limited to these ranges.

  The pressure-sensitive adhesive composition (plaster) obtained by the above method is spread on a release liner to a thickness of 100 to 250 μm through two rolls controlled at 100 to 200 ° C. with a calender coating machine. After spreading, a support is laminated to the anti-inflammatory analgesic patch.

  The hot melt method is a high-speed rotary mixer that can be controlled by heating. First, a styrene-isoprene-styrene block copolymer, a terpene resin, an antioxidant, and a plasticizer are added to a paste at 100 to 190 ° C. in a nitrogen atmosphere. Heat and stir at body temperature for 20 to 100 minutes to obtain a dissolved product. Thereafter, ferbinac as an active ingredient and nonyl acid vanillylamide or capsaicin as a warming sensation ingredient are added to the melt, and further heated and stirred at a paste temperature of 120 to 190 ° C. for 5 to 30 minutes for each ingredient. A pressure-sensitive adhesive composition having a uniform thickness is obtained. The temperature and time at the time of stirring are described with examples, and are not limited to these ranges.

  The pressure-sensitive adhesive composition (plaster) obtained by the above method was extruded from a die head part whose temperature was controlled at 100 to 200 ° C. with a hot melt coating machine and spread on a release liner to a thickness of 100 to 250 μm. After spreading, a support is laminated to the anti-inflammatory analgesic patch.

  With these methods, the anti-inflammatory analgesic patch of the present invention can be obtained, but the production method is not limited thereto.

  Examples of the support include a flexible support such as a film, nonwoven fabric, Japanese paper, cotton cloth, knitted fabric, and a laminate composite of nonwoven fabric and film. These supports are preferably made of a flexible material that can adhere to the skin and can follow the movement of the skin. Examples of the material of these supports include polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, cotton, acetate rayon, rayon, rayon / polyethylene terephthalate composite, polyacrylonitrile, polyvinyl alcohol, Acrylic polyurethane, ester polyurethane, ether polyurethane, styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-ethylene-propylene-styrene copolymer, styrene-butadiene rubber, ethylene-vinyl acetate Those having a copolymer, cellophane or the like as an essential component may be mentioned. As the support, a support in which no drug is adsorbed and no drug is released from the support side is preferable.

  Examples of the release liner include silicone-treated polyester film, silicone-treated polyethylene laminated fine paper, and silicone-treated glassine paper. The release liner is preferably made of a material that is difficult to absorb and adsorb drugs.

  EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.

(1) In vitro skin permeation test Under anesthesia with pentobarbital, the abdominal skin of hairless mice (male, 7 weeks old, 3 mice) was excised and mounted on a horizontal diffusion cell having a diameter of 20 mmφ. Hot water of 32 ° C. was circulated through the double-structured cell, the inside of the cell was kept at a constant temperature condition, and a test preparation punched to 15 mmφ was affixed to the stratum corneum side of the skin. The receiver was filled with purified water, sampled 0.5 ml over time while stirring with a stirrer, 0.5 ml of methanol was added to each sampled sample, stirred, centrifuged, and deproteinized The solution was quantified by HPLC (High Performance Liquid Chromatography) and the drug concentration was measured to determine the skin permeation rate. The receiver solution after sampling was supplemented with the same amount of purified water.

(2) Skin irritation One week before administration of the test substance, the back hairs of rabbits (male, 17 weeks old, 6 animals) were shaved with an electric clipper and shaved with an electric shaver. Thereafter, immediately before administration of the test substance, two 2.5 cm × 2.5 cm sections were made for each preparation on the shaved back, and one of the sections was filled with an injection needle [23G, Terumo Corporation]. Injured skin was prepared by injecting the test substance, and the test substance was administered to each of the healthy skin that was not damaged and one damaged skin. In order to prevent the test substance from falling off, the administration site was covered with gauze and fixed with an adhesive bandage (Elastopore, Nichiban) of about 5 × 5 cm. The sample was removed 24 hours after the administration, and the skin reaction 1 hour and 48 hours after the removal was visually observed. Skin reaction was evaluated according to the Draize criteria. That is, all the scores after 1 hour and 48 hours after removal (total of erythema, crust formation and edema formation in healthy skin and damaged skin) are added, and the total score is divided by 4 to calculate the average score for each individual Next, an average score for all animals was determined for each test substance, and the skin irritation index (PI) was obtained.

Evaluation criteria for Draize A: Erythema and scab formation Grade 0 No erythema Grade 1 Extremely mild erythema
Score 2 Clear erythema Score 3 Moderate to strong erythema Score 4 Strong erythema (crimson) with mild crust formation (deep injury)
B: Edema formation Grade 0 No edema Grade 1 Very mild edema (finally accepted)
Grade 2 Mild edema (distinguishable with a clear rise in the edge of the area)
Grade 3 moderate edema (swells over 1 mm)
Score 4 Strong edema (swells over 1 mm, spreads beyond the exposed area)

Skin irritation was evaluated according to the following safety category.
Safety category of primary skin irritation index Less than 2: Weak irritant 2 to 5: Moderate irritant 5 or more: Strong irritant

(3) Practical performance (irritation, smell)
A preparation prepared to a size of 7 cm × 10 cm was applied to the waist of five subjects, and the irritation feeling and the odor during use (at the time of application and during application) were evaluated according to the following criteria (5 levels or 4 levels). The scores obtained from each subject were averaged and used as the score of the preparation. For the sense of irritation, A is the case where the average value of the five-level evaluation is −1 to 1, B is the case where the average value of the five-level evaluation is −1 to 1 but the maximum score is 2, and the five levels. The case where the average value of evaluation was −1 or less or 1 or more was evaluated as C.

A: Stimulation (5 levels)
Score -2 None Score-1 Slightly weak Score 0 Just good irritation Score 1 Slightly strong Score 2 Stimulation is too strong and painful B: Smell (4 steps)
Score 0 None Score 1 Smell but no problem Score 2 Smell and anxious Score 3 Strong smell and dislike

[Example 1]
According to the calendar method, fervinac was 3.5% by mass, SIS 5229 [manufactured by JSR Co., Ltd.] was 30% by mass as a styrene-isoprene-styrene block copolymer, and YS resin PX1150N [Yasuhara Chemical Co., Ltd.] was used as a terpene resin. 21% by mass, Christol J352 (exxon mobile, liquid paraffin) as plasticizer, 45% by mass, and BHT (Seiko Chemical Co., Ltd., dibutylhydroxytoluene) as an antioxidant, 0.499. A uniform pressure-sensitive adhesive composition was prepared by kneading in an amount of 0.001% by mass of mass% and nonyl acid vanillylamide. Next, the pressure-sensitive adhesive composition was spread on a polyester film (thickness 75 μm) treated with silicone to a thickness of 150 μm to form a pressure-sensitive adhesive layer. On this adhesive layer, a polyester knitted fabric was laminated as a support to prepare an anti-inflammatory analgesic patch.

[Example 2]
In the hot melt method, 5% by mass of ferbinac, 15% by mass of quintac 3460C (manufactured by Nippon Zeon Co., Ltd.) as a styrene-isoprene-styrene block copolymer, Quintac 3520 [Nippon Zeon Co., Ltd.] 15% by mass, YS resin PX1150N (manufactured by Yashara Chemical Co., Ltd.) as the terpene resin, 14.5% by mass, and Haicol M-352 (manufactured by Kaneda Corp., liquid paraffin) as the plasticizer, 50% by mass, A uniform pressure-sensitive adhesive composition is prepared by heating and stirring with an antioxidant of 0.497% by mass of BHT [manufactured by Seiko Chemical Co., Ltd., dibutylhydroxytoluene] and 0.003% by mass of nonyl acid vanillylamide. did. Next, the pressure-sensitive adhesive composition was spread on a polyester film (thickness 75 μm) treated with silicone to a thickness of 100 μm to form a pressure-sensitive adhesive layer. A polyester knitted fabric was laminated as a support on the pressure-sensitive adhesive layer to prepare an anti-inflammatory analgesic patch.

[Example 3]
According to the hot melt method, felbinac is 3.5% by mass, quintac 3520 (manufactured by Nippon Zeon Co., Ltd.) as a styrene-isoprene-styrene block copolymer is 20% by mass and SIS 5002 (manufactured by JSR Co., Ltd.). 10% by mass, YS resin PX1150N (manufactured by Yashara Chemical Co., Ltd.) as a terpene resin, 20% by mass, Hycol M-352 (manufactured by Kaneda Corp., liquid paraffin) as a plasticizer, and BHT as an antioxidant A uniform pressure-sensitive adhesive composition was prepared by heating and stirring with a formulation of 0.495% by mass of [Seiko Chemical Co., Ltd., dibutylhydroxytoluene] and 0.005% by mass of nonyl acid vanillylamide. Next, the pressure-sensitive adhesive composition was spread on a polyester film (thickness 75 μm) treated with silicone to a thickness of 150 μm to form a pressure-sensitive adhesive layer. A polyester knitted fabric was laminated as a support on the pressure-sensitive adhesive layer to prepare an anti-inflammatory analgesic patch.

[Comparative Example 1]
An anti-inflammatory analgesic patch was prepared in the same manner as in Example 1 except that the BHT content was 0.493 mass% and the nonylic acid vanillylamide content was 0.007 mass% by the calender method. did.

[Comparative Example 2]
In the calendering method, instead of terpene resin, pine crystal KE-311 (Arakawa Chemical Co., Ltd., hydrogenated rosin ester resin) was used at a ratio of 21% by mass, and the BHT content was 0.495%. %, And an anti-inflammatory analgesic patch was prepared in the same manner as in Example 1 except that the content of nonylic acid vanillylamide was 0.005% by mass.

[Comparative Example 3]
In the calendering method, instead of the terpene resin, Pine Crystal KE-311 (Arakawa Chemical Co., Ltd., hydrogenated rosin ester resin) was used at a ratio of 21% by mass, and the BHT content was 0.492% by mass. %, And an anti-inflammatory analgesic patch was prepared in the same manner as in Example 1 except that the content of nonylic acid vanillylamide was 0.008% by mass.

[Comparative Example 4]
In the calendering method, 40% by mass of Haicol M-352 (manufactured by Kaneda Corp., liquid paraffin) as a plasticizer was used, the BHT content was 0.495% by mass, and nonyl acid vanillylamide was 0.005% by mass. In addition, an anti-inflammatory analgesic patch was prepared in the same manner as in Example 1 except that crotamiton [Kongo Chemical Co., Ltd.] was blended at a ratio of 5% by mass in order to enhance drug solubility.

[Comparative Example 5]
In the calendering method, 41% by mass of Hicol M-352 (manufactured by Kaneda Corp., liquid paraffin) as a plasticizer was used, the BHT content was 0.495% by mass, and nonyl acid vanillylamide was 0.005% by mass. %, And an anti-inflammatory analgesic patch was prepared in the same manner as in Example 1 except that 4% by mass of 1-menthol [Watanabe Chemical Co., Ltd.] was blended.

<Performance Evaluation of Examples and Comparative Examples>
The performance evaluation of the transdermal patches obtained in the above Examples and Comparative Examples was performed, and the results are shown in Table 1.

(* 1): Hairless mouse abdominal excised skin (* 2): I. I. Safety classification (less than 2: weak irritant, 2 or more, less than 5: moderate irritant, 5 or more: strong irritant)
(* 3): 5 levels (-2: None, -1: Slightly weak, 0: Just good stimulation, 1: Slightly strong, 2: Stimulation is too strong and hurts)
(* 4): A ... The average value of 5-level evaluation is -1 to 1, B ... The average value of 5-level evaluation is -1 to 1, but the maximum score is 2, C ... The average value of 5-level evaluation is -1 or less or 1 or more (* 5): 4 stages (0: none, 1: there is an odor but there is no problem, 2: there is an odor, and there is no concern, 3: the odor is strong and disgusting)

[Discussion]
As is apparent from the results in Table 1, the anti-inflammatory analgesic patches (Examples 1 to 3) prepared using the terpene resin YS resin PX1150N as the tackifier resin were rosin resin pine shown in Comparative Example 2. Felvinac showed good skin permeability at the same level as the anti-inflammatory analgesic patch prepared using Crystal KE-311. Furthermore, in any case where 0.001% by mass (Example 1), 0.003% by mass (Example 2), and 0.005% by mass (Example 3) of nonyl acid vanillylamide which is a warming sensation component Also, the feeling of irritation was good, and the evaluation point was small and the evaluation point was small. On the other hand, the patch of Comparative Example 1 containing 0.007% by mass of nonyl acid vanillylamide, which is a warming sensation stimulating component, has a strong irritation and uses rosin resin pine crystal KE-311 as a tackifying resin. In this case, even when the content of nonyl acid vanillylamide, which is a warming sensation component, is 0.005% by mass (Comparative Example 2), the irritation is somewhat strong, and some subjects may feel a strong irritation, and the maximum score is The patch was attached. Moreover, when the content of nonylic acid vanillylamide was increased to 0.008% by mass as in Comparative Example 3, the irritation feeling was even stronger. A patch of Comparative Example 4 containing 5% by mass of crotamiton with high drug solubility is a comparative example containing 4% by mass of 1-menthol having slightly low in vitro skin permeability and irritation and having a cooling sensation effect. The patch of No. 5 had low in vitro skin permeability and bad odor evaluation in practical evaluation.

  The anti-inflammatory analgesic patch provided with the adhesive layer containing felbinac of the present invention is used as an anti-inflammatory analgesic patch capable of percutaneously absorbing felbinac by being applied to the skin surface of the affected part (local tissue). be able to.

Claims (4)

In the anti-inflammatory analgesic patch provided with a pressure-sensitive adhesive layer containing felbinac on one side of the support, the pressure-sensitive adhesive layer comprises:
(A) styrene-isoprene-styrene block copolymer,
(B) terpene resin,
(C) a plasticizer,
(D) an antioxidant,
An anti-inflammatory analgesic patch comprising (e) felbinac, and (f) at least one warming stimulant component selected from the group consisting of nonylic acid vanillylamide and capsaicin.   The anti-inflammatory analgesic patch according to claim 1, wherein the adhesive layer does not contain rosin resin, crotamiton, and 1-menthol.   The anti-inflammatory analgesic patch according to claim 1, wherein the pressure-sensitive adhesive layer contains nonyl acid vanillylamide in a proportion of 0.005% by mass or less based on all components constituting the pressure-sensitive adhesive layer.   The anti-inflammatory analgesic patch according to claim 1, wherein the pressure-sensitive adhesive layer contains capsaicin in a proportion of 0.01% by mass or less based on all components constituting the pressure-sensitive adhesive layer.