JP6867210B2 - Patch - Google Patents

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 drug, is provided on one side of a support. The anti-inflammatory analgesic patch of the present invention can administer felbinac percutaneously into local tissues with good skin permeability, and even when the patch area is small, it does not cause discomfort to the patient and gives an appropriate warmth. The irritation (feeling of effectiveness) can be maintained.

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

Drugs such as non-steroidal anti-inflammatory drugs have medicinal effects such as anti-inflammatory and analgesic effects, but they do not have a stimulating sensation to feel the effects. Therefore, in many transdermal non-steroidal anti-inflammatory analgesic patches, ingredients with stimulating effects such as L-menthol, DL-menthol, DL-camphor, peppermint oil, capsaicin, capsicum extract, and nonylate vanillylamide are added. Therefore, it is common practice to impart a cooling sensation stimulating effect or a warm sensation stimulating effect.

In particular, warm sensation stimulating components such as capsaicin, capsicum extract, and nonyl acid vanillyl amide that exert a warm sensation stimulating effect are almost odorless and are often used as transdermal absorbents having little odor.

For example, a transdermal preparation in which a transdermal preparation containing felbinac and a nonyl acid vanillylamide as a warming component is blended is also known. Japanese Patent Application Laid-Open No. 2008-179564 (Patent Document 1) discloses a patch containing felbinac, a terpene-based tackifier resin, and nonyl acid vanillylamide.
Here, in the examples of Patent Document 1, fervinac, a styrene-isoprene-styrene block copolymer as a pressure-sensitive adhesive base, a terpene-based pressure-sensitive adhesive resin, and nonyl acid as a warming stimulating component are used on one side of a support. ^{A terpene-based adhesive was provided with a 70 cm 2} (7 cm × 10 cm) adhesive layer provided with an adhesive layer containing vanillylamide and the like, whereas the adhesive gave a good stimulating feeling (Examples 1 to 3). It has been shown that a similar patch using a rosin-based tackifier resin instead of the imparting resin gave poor results in the evaluation of irritation (Comparative Example 2).

Japanese Patent Application Laid-Open No. 2008-179564

^{A patch having a sticking area of about 70 cm 2} (7 cm × 10 cm) as described in Patent Document 1 is a patch of a general size that has been conventionally used, but these relatively large sticking areas The patch was not always easy to use because it was easy to wrinkle when it was applied to the skin. Therefore, a small patch having a small sticking area that is easy to stick to the skin is desired.

However, if the sticking area is reduced, the feeling of effectiveness is naturally reduced, and as a result, the duration of the feeling of effectiveness is also shortened. On the other hand, if the amount of the warmth stimulating component is increased, the effect will last longer, but if the amount of the warming stimulating component is too large, the warming stimulus immediately after application is too strong and some patients cannot tolerate the patch. There was a problem that it might have to be peeled off.

Therefore, in the pressure-sensitive adhesive layer containing fervinac, styrene-isoprene-styrene block copolymer as a pressure-sensitive adhesive base, terpene-based pressure-sensitive adhesive resin, etc., 0.004% by mass or more of a warming stimulating component, which is larger than usual, is used. When a small patch was prepared, an excessive warming stimulus was not given, but the effect of the warming stimulus lasted for about 2 hours, which was not long.

Therefore, the subject of the present invention is that in a small anti-inflammatory analgesic patch provided with an adhesive layer containing felbinac, the effect of an appropriate warming stimulus is long without giving an excessive warming stimulus. The purpose is to provide a sustainable patch.

As a result of diligent research to solve the above problems, the present inventors have conducted ferbinac, a styrene-isoprene-styrene block copolymer as an adhesive base, and a warmth of 0.01% by mass or more, which is higher than usual. When a small patch was prepared using a rosin-based tackifier resin in the pressure-sensitive adhesive layer containing a stimulating component, the case where a terpene-based tackifier resin was used without giving an excessive warming stimulus. In contrast, they have found that the effect of an appropriate warming stimulus can be sustained for a long time (about 6 to 8 hours), and completed the present invention.

That is, the present invention
[1] In an anti-inflammatory analgesic patch provided with a pressure-sensitive adhesive layer containing felbinac on one side of a support, the pressure-sensitive adhesive layer is formed.
(A) Styrene-isoprene-styrene block copolymer,
(B) Rosin-based adhesive resin,
(C) Softener,
(D) Antioxidant,
At least one selected from the group consisting of (e) felbinac and (f) nonylate vanillylamide and capsaicin and pepper extract in the range of 0.01% by mass to 0.05% by mass based on the total mass of the pressure-sensitive adhesive layer. Anti-inflammatory analgesic patch containing the warmth stimulating ingredient of
[2] The anti-inflammatory analgesic patch according to the above [1], which contains the warmth stimulating component in the range of 0.01% by mass to 0.03% by mass based on the total mass of the pressure-sensitive adhesive layer.
[3] The anti-inflammatory analgesic patch according to the above [1] or the above [2], which has a sticking area in ^{the range of 5 cm 2 to} 50 cm ^2.
[4] The anti-inflammatory analgesic patch according to any one of the above [1] to the above [3], wherein the rosin-based tackifier resin is a hydrogenated rosin-based tackifier resin.

In the anti-inflammatory analgesic patch of the present invention in which an adhesive layer containing felbinac, which is a non-steroidal anti-inflammatory analgesic, is provided on one side of a support, the adhesive layer is a styrene-isoprene-styrene block copolymer, rosin-based adhesive. Selected from the group consisting of vanillylamide nonylate and capsaicin and capsicum extract in the range of 0.01% by mass to 0.05% by mass based on the total mass of the imparting resin, softener, antioxidant, felbinac, and pressure-sensitive adhesive layer. By containing at least one kind of warm sensation stimulating component, the effect can be maintained without causing excessive warm sensation stimulus.

It is a graph which shows the sustainability of the effect feeling of the patch of Example 1 and Comparative Example 1.

The anti-inflammatory analgesic patch of the present invention is an anti-inflammatory analgesic patch in which a pressure-sensitive adhesive layer containing felbinac is provided on one side of a support.
(A) Styrene-isoprene-styrene block copolymer,
(B) Rosin-based adhesive resin,
(C) Softener,
(D) Antioxidant,
At least one selected from the group consisting of (e) felbinac and (f) nonylate vanillylamide and capsaicin and pepper extract in the range of 0.01% by mass to 0.05% by mass based on the total mass of the pressure-sensitive adhesive layer. It is characterized by containing a warming stimulating component of.

As the felbinac as a medicinal ingredient used in the present invention, a commercially available product can be used.
The content of felbinac is not particularly limited, but is preferably 0.3 to 10% by mass, more preferably 0.5 to 5% by mass, based on the total mass of the pressure-sensitive adhesive layer.

The styrene-isoprene-styrene block copolymer used in the present invention has a role of imparting adhesiveness to the pressure-sensitive adhesive layer, retaining each component in the pressure-sensitive adhesive layer, and dissolving or dispersing other components. is there. The content of the styrene-isoprene-styrene block copolymer is preferably 10 to 40% by mass based on the total mass of the pressure-sensitive adhesive layer from the viewpoints of tackiness, retention of other components, dispersibility of fervinac, and the like. , More preferably 20 to 35% by mass.

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 the styrene-isoprene-styrene block copolymer is too large, the adhesive strength is lowered, each component in the pressure-sensitive adhesive layer is made non-uniform, or each component is mixed and the pressure-sensitive adhesive composition is applied. It tends to cause a decrease in workability in work.

The styrene-isoprene-styrene block copolymer used in the present invention is not particularly limited, and commercially available ones may be used. Commercially available styrene-isoprene-styrene block copolymers include ZEON CORPORATION's trade name Quintac 3520, 3530, 3421, JSR Corporation's trade name SIS5000, 5002, 5229, and Kraton Polymer. There is a brand name Kraton D (SIS) series manufactured by Japan Co., Ltd. Further, these may be used alone or in a combination of two or more kinds.

The styrene content of the styrene-isoprene-styrene block copolymer used in the present invention is not particularly limited, but is preferably 10% to 30%, more preferably 13% to 26%.

The rosin-based tackifier resin is a rosin or a rosin derivative, and rosin ester, hydrogenated rosin ester, hydrogenated rosin lyserine ester and the like can be used, and hydrogenated rosin ester is preferable, and hydrogenated rosin lyserine ester is more preferable.
The softening point of the rosin-based tackifier resin used in the present invention is not particularly limited, but is preferably 80 ° C. to 110 ° C., more preferably 90 ° C. to 110 ° C., and even more preferably 95 ° C. to 105 ° C.

As the rosin-based tackifier resin used in the present invention, a commercially available one may be used, and as a specific commercially available rosin-based tackifier resin, a trade name ester gum manufactured by Arakawa Chemical Industry Co., Ltd., Examples include pencils, superesters and pine crystals.

As the rosin-based tackifier resin that can be used in the present invention, those listed above can be used alone, or two or more kinds can be used in combination.
The amount of the rosin-based tackifier resin used is preferably 20 to 40% by mass, more preferably 25 to 35% by mass, based on the total mass of the pressure-sensitive adhesive layer.

The softening agent used in the present invention is not particularly limited, but vegetable oil, liquid polyisobrene, liquid polybutene, liquid paraffin and the like can be used, and liquid paraffin is more preferable.
The amount of the softener used is preferably 30 to 50% by mass, more preferably 35 to 45% by mass, based on the total mass of the pressure-sensitive adhesive layer.

As the antioxidant used in the present invention, known ones can be used, and the antioxidant is not particularly limited, but dibutylhydroxytoluene is preferable.
The amount of the antioxidant used is preferably 0.1 to 30% by mass, more preferably 0.1 to 1% by mass, based on the total mass of the pressure-sensitive adhesive layer.

As at least one warm sensation stimulating component selected from the group consisting of nonylic acid vanillylamide, capsaicin, and capsicum extract used in the present invention, commercially available ones can be used. Nonyl acid vanillyl amide is more preferred.
The amount of the warmth stimulating component used is in the range of 0.01 to 0.05% by mass based on the total mass of the pressure-sensitive adhesive layer, but this amount is usually 70 cm ² (7 cm × 10 cm) on the market. It will be larger than the amount used in the patch in the front and back sticking areas. The range of the preferable amount of the warm sensation stimulating component is 0.015 to 0.04% by mass, 0.01 to 0.03% by mass, 0.015 to 0.03% by mass, and the like.

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 tackifier resin, an antioxidant and fervinac are kneaded with a pressure kneader at 100 to 150 ° C. for 10 to 30 minutes, and then the plasticizer is applied several times. The mixture is divided into two portions to continue kneading, and finally nonylate vanillylamide is added and kneaded for another 5 to 20 minutes to obtain a pressure-sensitive adhesive composition in which each component is uniform. The temperature and time at the time of kneading are described by way of example, 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 whose temperature is controlled to 100 to 200 ° C. using a calendar coating machine. After spreading, a support is laminated on this to prepare an anti-inflammatory analgesic patch.

The hot melt method is a high-speed rotary mixer with heat control, in which styrene-isoprene-styrene block copolymer, tackifier resin, antioxidant, and softener are first applied in a nitrogen atmosphere at 100 to 190 ° C. Heat at body temperature for 20 to 100 minutes and stir at high speed to obtain a lysate. Then, felbinac, which is an active ingredient, and vanillylamide nonylate, which is a warming stimulant ingredient, or capsaicin are added to the melt, and each component is further heated at a plaster temperature of 120 to 190 ° C. for 5 to 30 minutes and stirred at high speed. To obtain a pressure-sensitive adhesive composition in which is uniform. The above-mentioned temperature and time during stirring have been described by way of example, and are not limited to these ranges.

The pressure-sensitive adhesive composition (plaster) obtained by the above method is extruded from a die head portion whose temperature is controlled to 100 to 200 ° C. by 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 on this to prepare an anti-inflammatory analgesic patch.

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

Examples of the support include a flexible support such as a film, a non-woven fabric, Japanese paper, a cotton cloth, a knitted cloth, and a laminated composite of a non-woven fabric and a 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, and the like. 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 Examples thereof include those containing a copolymer, cellophane, etc. as essential components. As the support, it is preferable that the drug is not adsorbed and the drug is not released from the support side.

Examples of the release liner include a silicone-treated polyester film, a silicone-treated polyethylene-laminated wood-free paper, and a silicone-treated glassine paper. The release liner is preferably made of a material that does not easily absorb or adsorb the drug.

The sticking area of the patch of the present invention is smaller than that of a normal commercially available patch with a sticking area of about 70 cm ² (7 cm × 10 cm), and 5 cm ^{2 to} 50 ^{cm 2} is preferable in consideration of ease of sticking. 5cm ² ~40cm ² is more preferable.

Example 1
25.0% by mass of SIS5229 (styrene content 15%) manufactured by JSR Co., Ltd. as a styrene-isoprene-styrene block copolymer, and pine manufactured by Arakawa Chemical Industry Co., Ltd. as a rosin-based tackifier resin. Crystal KE-311 (hydrogenated rosin styrene ester, softening point 90-100 ° C) is 31.5% by mass, and as a softening agent, Kaneda Co., Ltd.'s trade name Hicol M352 (liquid paraffin) is 38.0% by mass, an antioxidant. BHT (dibutylhydroxytoluene) was added in an amount of 0.5% by mass, fernabic was added in an amount of 5.0% by mass, and wanylamide nonylate was added in an amount of 0.02% by mass. A suitable pressure-sensitive adhesive composition was prepared. Next, the pressure-sensitive adhesive composition was spread on a silicone-treated polyester film (thickness 75 μm) to a thickness of 100 μm to form a pressure-sensitive adhesive layer. A polyester-based knitted cloth was laminated on the pressure-sensitive adhesive layer as a support ^{and cut so as to have a sticking area of 36 cm 2} (6 cm × 6 cm) to prepare an anti-inflammatory and pain-relieving patch.

Comparative example 1
25.0% by mass of SIS5229 (styrene content 15%) manufactured by JSR Co., Ltd. as a styrene-isoprene-styrene block copolymer, and YS manufactured by Arakawa Chemical Industry Co., Ltd. as a terpene adhesive resin. Resin PX1150N (terpene resin, softening point 115 ° C) is 31.5% by mass, Kaneda Co., Ltd. brand name Hicol M352 (liquid paraffin) is 38.0% by mass as a softening agent, and Yakuzo BHT (dibutyl) is used as an antioxidant. (Hydroxytoluene) was blended in 0.5% by mass, fernavik in 5.0% by mass, and nonylate vanilamide in 0.004% by mass, and the compounding formulation was heated and stirred by a hot melt method to obtain a uniform pressure-sensitive adhesive composition. Prepared. Next, the pressure-sensitive adhesive composition was spread on a silicone-treated polyester film (thickness 75 μm) to a thickness of 100 μm to form a pressure-sensitive adhesive layer. A polyester-based knitted cloth was laminated on the pressure-sensitive adhesive layer as a support ^{and cut so as to have a sticking area of 36 cm 2} (6 cm × 6 cm) to prepare an anti-inflammatory and pain-relieving patch. This is the same as in Example 1 except that YS resin PX1150N, which is a terpene-based pressure-sensitive adhesive resin, is used instead of the rosin-based pressure-sensitive adhesive resin, and the blending amount of nonylate vanilamide is 0.004% by mass.

Comparative Example 2
25.0% by mass of SIS5229 (styrene content 15%) manufactured by JSR Co., Ltd. as a styrene-isoprene-styrene block copolymer, and YS manufactured by Arakawa Chemical Industry Co., Ltd. as a terpene adhesive resin. Resin PX1150N (terpene resin, softening point 115 ° C) is 31.5% by mass, Kaneda Co., Ltd. brand name Hicol M352 (liquid paraffin) is 38.0% by mass as a softening agent, and Yakuzo BHT (dibutyl) is used as an antioxidant. (Hydroxytoluene) was blended in 0.5% by mass, fernavik in 5.0% by mass, and nonylate vanilamide in 0.02% by mass, and the compounding formulation was heated and stirred by a hot melt method to obtain a uniform pressure-sensitive adhesive composition. Prepared. Next, the pressure-sensitive adhesive composition was spread on a silicone-treated polyester film (thickness 75 μm) to a thickness of 100 μm to form a pressure-sensitive adhesive layer. A polyester-based knitted cloth was laminated on the pressure-sensitive adhesive layer as a support ^{and cut so as to have a sticking area of 36 cm 2} (6 cm × 6 cm) to prepare an anti-inflammatory and pain-relieving patch. This is the same as in Example 1 except that YS resin PX1150N, which is a terpene-based pressure-sensitive adhesive resin, is used instead of the rosin-based pressure-sensitive adhesive resin. An attempt was made to evaluate the efficacy of the anti-inflammatory analgesic of Comparative Example 2 by a warm sensation stimulus by sensory evaluation, but all 11 evaluators felt pain 10 to 20 minutes after application and had to remove the application. So the evaluation was stopped.

スコアは評点５を１００点とし、評点が１増える減るごとに２０点ずつ減少する。評価
は１１名で行いその平均値を平均スコアとした。 Test Example 1
The effect of the anti-inflammatory analgesic patch prepared above in Example 1 and Comparative Example 1 due to the warm sensation was evaluated by sensory evaluation.
The method for evaluating the effect of the warmth stimulus was as follows.
The evaluation indexes and scores on the scores 0 to 10 were set as follows, and the effect of each anti-inflammatory and pain-relieving patch by the warm sensation was scored.
Here, a score of 5 is the most comfortable, a score of 10 is too strong, and a score of 0 is ineffective.

The score is set to 100 points with a score of 5, and decreases by 20 points as the score increases or decreases by 1. The evaluation was performed by 11 people, and the average value was used as the average score.

Table 2 and FIG. 1 show the average scores of the effects of warmth stimulation at 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours after applying the anti-inflammatory analgesic patch obtained in Example 1 and Comparative Example 1. Indicated.

From Table 2 and FIG. 1, the anti-inflammatory analgesic patch of Example 1 using the rosin-based ester has a longer duration of efficacy and is better than the anti-inflammatory analgesic patch of Comparative Example 1 using the terpene resin. It was confirmed that there was.
Neither the anti-inflammatory analgesic patch of Example 1 and Comparative Example 1 gave an excessive warming stimulus.

Claims (4)

In an anti-inflammatory analgesic patch provided with a felbinac-containing pressure-sensitive adhesive layer on one side of a support, the pressure-sensitive adhesive layer is
(A) Styrene-isoprene-styrene block copolymer,
(B) Rosin-based adhesive resin,
(C) Softener,
(D) Antioxidant,
At least one selected from the group consisting of (e) felbinac and (f) nonylate vanillylamide and capsaicin and capsicum extract in the range of 0.01% by mass to 0.05% by mass based on the total mass of the pressure-sensitive adhesive layer. An anti-inflammatory analgesic patch containing the warmth stimulating component of (however, the adhesive layer does not contain a terpene resin) . The anti-inflammatory analgesic patch according to claim 1, wherein the warm sensation stimulating component is contained in the range of 0.01% by mass to 0.03% by mass based on the total mass of the pressure-sensitive adhesive layer. The anti-inflammatory analgesic patch according to claim 1 or ^{2, wherein} the sticking area is in ^{the range of 5 cm 2 to} 50 cm 2. The anti-inflammatory analgesic patch according to any one of claims 1 to 3, wherein the rosin-based tackifier resin is a hydrogenated rosin-based tackifier resin.

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