WO2001010435A1

WO2001010435A1 - Patch

Info

Publication number: WO2001010435A1
Application number: PCT/JP2000/005269
Authority: WO
Inventors: Eiichiro Manabe; Takashi Kamakura
Original assignee: Taisho Pharmaceutical Co., Ltd.; Teikoku Seiyaku Co., Ltd.
Priority date: 1999-08-05
Filing date: 2000-08-04
Publication date: 2001-02-15
Also published as: AU6319600A

Abstract

A patch comprising a water-soluble polymer as the base, characterized by containing a capsaicinoid and N-vanillylnonanamide in amounts per 100 g of the base of 0.0002 to 0.005 g and 0.0005 to 0.007 g respectively.

Description

Specification

Patch Technical Field

The present invention relates to a hypoallergenic warming patch. Conventional technology

Patches are an excellent dosage form in that the drug to be incorporated can be continuously transdermally administered. However, patches also have some problems. The most frequent of these problems is skin irritation occurring at the site where the patch was applied to patients. In particular, when a warming ingredient represented by pepper extract, nonyl acid phenylylamide, etc. is combined, it may further irritate the skin and cause rashes. .

An object of the present invention is to provide a patch having an excellent warming effect and less skin irritation. Disclosure of the invention

The present inventor has conducted intensive studies in view of the above-mentioned object, and as a result, when combined with cabsaicinoid and nonyluric acid perilylamide, a sufficient warm stimulus was obtained even at a low dose with little skin irritation. And found that the present invention was completed.

That is, the present invention relates to a patch containing a water-soluble polymer base, in which cabsaicinoid and nonyl acid penilylamide are blended, and the amount of capsaicinoid in 100 g of the base is [X] (g). Assuming that the blending amount of nonyl acid penilylamide is [Y] (g), [X] is 0.002 to 0.05 and [Y] is 0.0005 to 0.05. A patch characterized in that the patch is 07.

Further, the present invention provides a patch containing a water-soluble polymer base, in which cabsaicinoid and nonyl acid penilylamide are blended, and the amount of the capsaicinoid in 100 g of the base is [X] (g). Assuming that the blending amount of nonyl acid penilylamide is [Y] (g), [Y] is 0.005 to 0.003, and [X] +0.6 X [Y] Is 0.0000 to 0.0208.

In addition, the present invention provides a patch containing a water-soluble polymer base, in which cabsaicinoid and nonyl acid penilylamide are compounded, and the amount of capsaicinoid in 100 g of the base is [X] (g). , The amount of nonyl acid penilylamide is [Y] (g) Wherein [Y] is 0.0005 to 0.007, and [Χ] + 0.6 X [Υ] is 0.0046 to 0.0052. . Embodiment of the Invention

The present invention is characterized in that cabsaicinide and nonyl acid penilylamide are blended in a water-soluble polymer base, and that the blending amount is set to a low dose.

(Warmth ingredient)

In the present invention, capsaicinoid means capsaicin and homologues thereof, and specific examples include capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin and the like.

In addition, the turnip cycinoid is preferably derived from a pepper, and may include pepper shakes, pepper powder, and pepper tincture.

When the compounding amount of cabsaicinoid per 100 g of base is [X] (g), [X] is preferably 0.0002 or more from the viewpoint of warming effect and 0.005 or less from the viewpoint of reducing skin irritation. .

When the amount of nonyl acid penilylamide per 100 g of base is [Y] (g), [Y] is preferably 0.0005 or more from the viewpoint of warm feeling effect, and from the viewpoint of reducing skin irritation. It is preferably 0.007 or less. Furthermore, [Y] is preferably 0.0005 to 0.003 in the patch for treating stiff shoulder, and [Y] is preferably 0.0005 to 0.007 in the patch for treating back pain.

Further, the present inventor found that the effect of imparting warmth of nonyl acid penilylamide was about 0.6 times that of cabsaicinide, and conducted a test based on this finding. [関係] + 0.6 ヮ [ヮ] is preferably in the range of 0.0002 to 0.0028 in the patch for the treatment of stiff shoulder in the patch for the treatment of low back pain. It was confirmed that [Χ] +0.6 X [Υ] was preferably in the range of 0.0046 to 0.0052.

(Water-soluble polymer base)

In the present invention, the composition of the water-soluble polymer base is not particularly limited, and any composition may be used. For example, gelatin, polyacrylic acid, polyacrylic acid salts such as sodium polyacrylate, partially neutralized polyacrylic acid, starch polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid copolymer, hydroxypropyl Cellulose, carmellose sodium, methylcellulose, Examples thereof include a maleic anhydride copolymer, an N-vinyl acetate copolymer, and a methacrylic acid copolymer. The water content of the water-soluble polymer base is preferably 35 to 80% by weight based on the whole base in view of the cooling effect when applied.

(Other ingredients)

In addition to the essential ingredients, the present invention is also applicable to the following ingredients: menthol, menthol, heart oil, forceful, maleink mouth feniramine, diphenhydramine hydrochloride, azulene, sodium guaizulene sulfonate, glycyrrhetinic acid Drugs such as glycyrrhizic acid and its salts, tocopherol acetate, and d1-camphor can also be added. In addition to the above components, commonly used base components such as excipients (silicic acid anhydride, kaolin, cyclodextrin, zinc oxide, titanium oxide, aluminum silicate moisturizer, etc.), moisturizers (glycerin, diglycerin, Synthetic high molecular compounds such as triglycerin, propylene glycol, butylene glycol, polyethylene glycol, d_sorbitol, etc., adhesives (Ripoxyvinyl polymer, polyvinyl alcohol) or natural high molecular compounds such as gum arabic and xanthan cancer ), Surfactants (glycerin fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hardened castor oil, sorbin fatty acid ester, polysorbate 80, polysorbate 60, sorbitan sesquioleate, etc.) Can be formulated aluminum hydroxide, aluminum glycinate, dihydroxy aluminum § amino acetate, such as polyvalent metal compounds such as synthetic hydrotalcite), and the like.

Further, if necessary, an absorption promoter, a preservative, an antioxidant, a coloring agent, and the like can be added.

(Support)

The patch of the present invention can be spread on a support, a liner, or the like used for a conventional patch to form a patch by a usual method. The support is a flexible woven fabric, nonwoven fabric, film, or sheet, and particularly preferably a breathable material having elasticity in all directions. Industrial applicability

ADVANTAGE OF THE INVENTION By this invention, it became possible to provide the patch which is excellent in a warm feeling effect and has little skin irritation. BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1 (Patch for stiff shoulder treatment)

Polyethylene glycol 4.0 parts by weight, paraoxybenzoic acid ester 0.15 parts by weight, 1.1 menthol 0.25 parts by weight, indomethacin 0.375 parts by weight, Pepper extract (cubacinoid concentration is 20% by weight of the whole pepper extract) 0. 01 parts by weight, nonyl acid penilylamide 0.001 parts by weight, concentrated glycerin 23 parts by weight, metal metasilicate aluminate 0.08 parts by weight uniformly dispersed to form one liquid <Gelatin 1.0 parts by weight, polyvinyl alcohol 3 20 parts by weight, carmellose sodium 3.00 parts by weight, sodium polyacrylate 5.0 parts by weight, hydroxypropylcellulose 0.3 parts by weight, 70% D-sorbitol 14 parts by weight, force oil 3.0 parts by weight, Tartaric acid (1.2 parts by weight), sodium edetate (0.1 parts by weight), and an appropriate amount of purified water were uniformly dispersed, and one liquid was added and mixed uniformly to obtain a plaster for patch. This was uniformly spread on a nonwoven fabric, and a patch was obtained by an ordinary method. Examples 2 to 8 were prepared in the same manner as in Example 1 with the following compositions. Components not shown in the table were blended in the same amounts as in Example 1. Table 1 (Unit: parts by weight)

Example 9

Black mittens 2.0 parts by weight, paraoxybenzoic acid ester 0.05 parts by weight, 1-menthol 0.25 parts by weight, indomethacin 0.375 parts by weight, red pepper (capsaicinoid concentration is 20 weight parts of the whole pepper extract) %) 0.01 Parts by weight, 0.001 part by weight of nonyl acid penilylamide, 23 parts by weight of concentrated glycerin, and 0.08 parts by weight of dihydroxyaluminum aminoacetate were uniformly dispersed to form one liquid. Castor oil 1.0 part by weight, polyvinyl alcohol 2.0 parts by weight, starch acrylate 2.5 parts by weight, sodium polyacrylate 6.0 parts by weight, hydroxypyrucel cellulose 0.3 parts by weight, propylene glycol 15 Parts by weight, 3.0 parts by weight of kaolin, 0.6 parts by weight of tartaric acid, 0.5 parts by weight of silicon dioxide, and an appropriate amount of purified water are uniformly dispersed, and one liquid is added and mixed uniformly to obtain a plaster for a patch. Was. This was uniformly spread on a nonwoven fabric, and a patch was obtained by an ordinary method. Example 10

4.5 parts by weight of N-methyl-2-pyrrolidone, 0.05 parts by weight of paraoxybenzoic acid ester, 0.25 parts by weight of 1-menthol, 0.375 parts by weight of indomethacin, Pepper extract (The concentration of cabsaicinoid is 20% of the total amount of pepper extract. (Weight%) 0.01 part by weight, 0.001 part by weight of nonyl acid penilylamide, 20 parts by weight of concentrated glycerin, and 0.1 part by weight of aluminum hydroxide were uniformly dispersed to form one liquid. 3.0 parts by weight of polyvinyl alcohol, 6.0 parts by weight of sodium polyacrylate, 0.3 parts by weight of hydroxypropyl cellulose, 25 parts by weight of 70% D-sorbitol, 3.0 parts by weight of kaolin, 1.2 parts of tartaric acid Parts by weight, 0.12 parts by weight of sodium edetate, and an appropriate amount of purified water were uniformly dispersed, and one part of the solution was added and uniformly mixed to obtain a plaster for a patch. This was uniformly spread on a nonwoven fabric, and a patch was obtained by an ordinary method. Example 1 1

4.0 parts by weight of polyoxyethylene sorbitan aliphatic ester, 0.05 parts by weight of paraoxybenzoic acid ester, 0.25 parts by weight of 1-menthol, 0.375 parts by weight of indomethacin, Capsicum extract 0.01% by weight, 0.001 part by weight of nonyl acid phenylylamide, 20 parts by weight of concentrated glycerin, 0.1 part by weight of synthetic hydrotalcite, 0.1 part by weight of butylhydroxytoluene Into one solution. 3.2 parts by weight of polyacrylic acid, 3.0 parts by weight of carmellose sodium, 5.0 parts by weight of sodium polyacrylate, 0.3 parts by weight of hydroxypropylcellulose, 20 parts by weight of 70% D-sorbitol, kaolin 3. 0 parts by weight, 1.2 parts by weight of tartaric acid, and an appropriate amount of purified water were uniformly dispersed, and one part of the solution was added and uniformly mixed to obtain a plaster for a patch. This is uniformly applied to the nonwoven fabric _C Example was spread was obtained by a conventional method patch 12

0.3 parts by weight of polyoxyethylene sorbitan aliphatic ester, 4.0 parts by weight of polyethylene glycol, 0.05 part by weight of paraoxybenzoate, 0.25 parts by weight of 1-menthol, 0.375 parts by weight of indomethacin Parts, Capsicum extract (concentration of capsaicinoid is 20% by weight of the total capsicum extract) 0.0 1 part by weight, nonyl acid penilylamide 0.001 part by weight, propylene glycol 20 parts by weight, dry aluminum hydroxide gel 0.08 parts by weight Parts were uniformly dispersed to form one liquid. 3.0 parts by weight of polyacrylic acid, 3.5 parts by weight of sodium carmellose, 5.0 parts by weight of sodium polyacrylate, 0.3 parts by weight of hydroxypropylcellulose, 15 parts by weight of 70% D_sorbitol, 3 parts by weight of kaolin 0.0 part by weight, 1.2 parts by weight of tartaric acid, 0.1 part by weight of sodium edetate and an appropriate amount of purified water were uniformly dispersed, and one liquid was added and mixed uniformly to obtain a plaster for patch. This was uniformly spread on a nonwoven fabric, and a patch was obtained by an ordinary method. Test example 1

The patches of Examples 1 to 4 and Comparative Example were applied to the right and left shoulders of three subjects. Each patch was evaluated for warmth, pleasure, effectiveness, and skin irritation when applied for 6 hours as follows, and the average value is shown in Table 2.

Very good 7 points: Good 6 points: Good 5 points

Normal 4 points: Somewhat bad 4 points: Bad 2 points

Very bad 1 point Table 2

① Warm feeling ② Comfortable ③ Effectiveness ④ Skin irritation Example 1 6.7 6.3 6.7 None

Scrap Example 2 5.7 6.0 5.7 None

Example 3 5.7 5.7 5.3 None

Example 4 6.3 6.3 6.3 None Test example 2

The patches of Examples 5 to 8 were applied to the lumbar regions of three subjects. Each patch was evaluated for warmth, pleasure, effectiveness, and skin irritation when applied for 6 hours in the same manner as in Test Example 1. The average value is shown in Table 3. Table 3

① Warm feeling ② Comfortable ③ Effectiveness 刺激 Stimulation of skin capture Example 5 5. 3 5. 3 5. 7 None

Waist Example 6 6. 3 6. 3 6. 3 None

5. 7 5. 3 5. 7 None

Example 8 6. 0 6. 3 6. 7 None

Claims

The scope of the claims

1. In a patch containing a water-soluble polymer base, blend cabsaicinoid and nonyl acid penilylamide, and mix the amount of cabsaicinoid with 100 g of base [X] (g) and nonyl acid penilylamide. A patch characterized in that when the amount is [Y] (g), [X] is 0.0002 to 0.005, and [Y] is 0.0005 to 0.007.

2. In a patch containing a water-soluble polymer base, cabsaicinoid and nonyl acid penilylamide are mixed, and the amount of cabsaicinoid per 100 g of the base is [X] (g), and the amount of nonyl acid penilylamide is mixed. Is [Y] (g), [Y] is 0.0005 to 0.003, and [X] +0.6 [丫] is 0.0002 to 00028. Agent.

3. In a patch containing a water-soluble polymer base, blend cabsaicinoid and nonyl acid penilylamide, and adjust the amount of cabsaicinoid to 100 g of the base with [X] (g) and nonyl acid penilylamide. When the quantity is [Y] (g), [Y] is 0.0005 to 0.007, and [X] +0.6 X [Y] is 0.0004 6 to 0.0005. A patch characterized in that:

4. The patch according to any one of claims 1 to 3, wherein the capsaicinoid is derived from a pepper.

5. The patch according to any one of claims 1 to 4, wherein the water-soluble polymer base contains 35 to 80% by weight of water based on the whole base.

6. The patch according to any one of claims 1 to 5, further comprising indomethacin.