JP2004168764A - Adhesive composition for patch preparation and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an adhesive for a patch preparation having a good adhering property to a subject to be adhered and little irritation to the skin, without generating released serous liquid, having a simple composition easy for adjustment and exhibiting a high percutaneous absorption of a medicine. <P>SOLUTION: The adhesive composition for patch preparation contains (A) a (meth)acrylic acid-based polymer expressed by formulae (1) and (2) (wherein, R<SP>1</SP>, R<SP>2</SP>are each independently H or methyl; and M is NH<SB>4</SB><SP>+</SP>or an alkali metal) and having a molar ratio of (1)/(2)=(100/0)-(90/10), (B) water, (C) a polyhydric alcohol and (D) an aluminum compound. The adhesive composition for patch preparation can contain much amount of the polyhydric alcohol among the skeleton of the adhesive layer, and forms a stable base substrate without releasing the serous liquid. The patch preparation by using the adhesive composition for the patch preparation is excellent in releasing characteristics and adhering property, and has a high safety. <P>COPYRIGHT: (C)2004,JPO

Description

  The present invention relates to an adhesive for a patch. More specifically, the release characteristics and adhesiveness of a (meth) acrylic acid polymer and a transdermal drug used in a transdermal absorption type external preparation are dispersed or dissolved in a high-concentration polyhydric alcohol aqueous solution. The present invention relates to an adhesive for a patch which is excellent and highly safe, and a method for producing the same.

  In recent years, it has been confirmed that alcohols such as polyhydric alcohols enhance the solubility and transdermal absorbability of drugs in oral vaginal mucosa preparations and transdermal absorption preparations for medical use. Therefore, it has been an issue to make the patch contain alcohol at a high concentration.

  In general, patches are classified into two types: nonaqueous preparations such as plasters and tapes, and hydrous preparations such as cataplasms. Acrylic and rubber-based adhesives are used as non-aqueous adhesives, but although their transdermal absorbability is good, their irritation to the skin is large due to their adhesive strength. It was difficult to apply, especially for drugs that need to be repeatedly applied. In addition, since the adhesive has no hydrophilic property, it is easily peeled off by sweat or body fluid, and a gap is formed between the skin and the preparation, resulting in a decrease in drug absorption. Further, acrylic polymers still have the problem of toxicity of residual monomers, especially when applied to the skin, causing residual skin irritation (for example, Journal of the Adhesion Society of Japan, 27, 526 (1991). ) (See Non-Patent Document 1)).

  On the other hand, water-containing preparations are generally synthesized from natural water-soluble polymers such as tragacanth gum, gum arabic, carrageenan, duran gum, sodium alginate, mannan, and gelatin, polyacrylic acid or polymethacrylate, polyvinyl alcohol, polyacrylamide, and the like. A polymer is used, and a humectant such as a polyhydric alcohol is blended with the polymer. Since these adhesive base materials are hydrophilic, they are less irritating to the skin and can be said to be suitable for long-term application.However, they are poor in adhesiveness, and basically the drugs absorbed from the skin are lipophilic. There are many. Therefore, the drug was hardly dissolved in the present preparation having a high water content, and as a result, the absorbability was poor. Further, it has been difficult to ensure the stability of the drug over time for drugs that are easily hydrolyzed.

  In order to avoid such a problem, for example, Japanese Patent Application Laid-Open No. 4-178323 (Patent Document 1) proposes dissolving polyacrylic acid in a polyhydric alcohol and cross-linking the same with magnesium metasilicate aluminate. .

  However, although polyacrylic acid can be expected to be hydrophilic and less irritating, the cross-linking reaction between aluminum and carboxyl groups hardly progresses because it does not substantially contain water, so that stickiness and so-called "paste residue" on the skin And the feeling of use was extremely poor. Further, although polyacrylic acid is soluble in glycerin, its viscosity is low, and as a result, it is difficult to increase the adhesive strength.

  Japanese Patent Application Laid-Open No. 6-128151 (Patent Document 2) discloses a polyacrylic acid represented by a specific general formula and / or a monovalent salt of polymethacrylic acid also represented by a specific general formula and polyacrylic acid. And / or a patch base composed of polymethacrylic acid, predetermined amounts of aluminum salt and alcohol. However, the alcohol affinity of the polymer shown here was low, and as the alcohol concentration was increased, the polymer was aggregated and further precipitated, so that no viscosity was exhibited, and as a result, no adhesive strength was exhibited.

JP-A-4-178323 JP-A-6-128151 Journal of the Adhesion Society of Japan, 27, 526 (1991)

  The present invention solves the above-mentioned problems of the prior art, and has a simple composition that is easy to adjust with a simple composition without stickiness to the adherend, little irritation to the skin and no syneresis. An object of the present invention is to provide a pressure-sensitive adhesive for a patch having high skin absorbability.

  In view of such circumstances, the present inventors have conducted intensive studies, and as a result, by using a specific (meth) acrylic acid-based polymer or a copolymer thereof and a polyhydric alcohol as main components, It has been found that the water content in the pressure-sensitive adhesive can be substantially reduced to 30% by mass or less, and that the pressure-sensitive adhesive for dermal patch using the same has excellent transdermal absorbability.

（式中、Ｒ¹およびＲ²は、各々独立して、水素原子またはメチル基を表わし、ＭはＮＨ₄ ⁺またはアルカリ金属を表わす。）
で示され、（１）／（２）＝１００／０〜９０／１０（モル比）である（メタ）アクリル酸系重合体（Ａ）、水（Ｂ）、多価アルコール（Ｃ）およびアルミニウム化合物（Ｄ）を含有し、水（Ｂ）の含有量が５〜３０質量％であることを特徴とする貼付剤用粘着剤組成物。
２．繰り返し単位が、一般式（１）および（２）

（式中の記号の意味は前記１の記載に同じ。）
である（メタ）アクリル酸系重合体（Ａ）の０．２質量％水溶液粘度が４００ｍＰａ・ｓ以上である前記１記載の貼付剤用粘着剤組成物。
３．多価アルコールが三価以上のアルコールである前記１記載の貼付剤用粘着剤組成物。
４．多価アルコールがグリセリンである前記３記載の貼付剤用粘着剤組成物。
５．多価アルコールの含有量が組成物全量に対して４０〜９４．５質量％である前記１に記載の貼付剤用粘着剤組成物。
６．アルミニウム化合物として水溶性のアルミニウム化合物および水酸化アルミナ・マグネシウムを併用する前記１記載の貼付剤用粘着剤組成物。
７．アルミニウム化合物の含有量が組成物全量に対して０．０１〜２０質量％である前記１記載の貼付剤用粘着剤組成物。
８．さらに、多価アルコールと親和性の高い高分子化合物（Ｅ）を含有する前記１記載の貼付剤用粘着剤組成物。
９．多価アルコールと親和性の高い高分子化合物（Ｅ）が、カルボキシビニルポリマーおよびＮ−ビニルアセトアミド−アクリル酸ナトリウム共重合体から選択される少なくとも一種である前記８記載の貼付剤用粘着剤組成物。
１０．多価アルコールと親和性の高い高分子化合物の含有量が、組成物全量に対して０.０１〜２０質量％である前記８または９記載の貼付剤用粘着剤組成物。
１１．薬効成分としてジクロフェナクナトリウムを含有する前記１乃至１０記載の貼付剤用粘着剤組成物。
１２．薬効成分としてカプサイシンを含有する前記１乃至１０記載の貼付剤用粘着剤組成物。
１３．繰り返し単位が、一般式（１）および（２）

（式中の記号の意味は前記１の記載に同じ。）
で示され、（１）／（２）＝１００／０〜９０／１０（モル比）である（メタ）アクリル酸系重合体（Ａ）、水（Ｂ）、多価アルコール（Ｃ）、アルミニウム化合物（Ｄ）を必須成分とし、所望により多価アルコールと親和性の高い高分子化合物（Ｅ）を含有し、水（Ｂ）の含有量が５〜３０質量％である貼付剤用粘着剤組成物の製造方法において、（メタ）アクリル酸系重合体（Ａ）と多価アルコール（Ｃ）の水（Ｂ）溶液とをそれらの総質量における水分濃度５０％以上として混合し、その後残りの成分（残りの多価アルコール（Ｃ）、アルミニウム化合物（Ｄ）および所望により高分子化合物（Ｅ））を添加混合し、水分の濃度を５〜３０％に調整していくことを特徴とする貼付剤用粘着剤組成物の製造方法。 That is, the present invention relates to the following pressure-sensitive adhesive composition for patches and a method for producing the same.
1. When the repeating unit has the general formula (1) or (2)

(In the formula, R ¹ and R ² each independently represent a hydrogen atom or a methyl group, and M represents NH ₄ ⁺ or an alkali metal.)
Wherein (1) / (2) = 100/0 to 90/10 (molar ratio), (meth) acrylic acid-based polymer (A), water (B), polyhydric alcohol (C) and aluminum A pressure-sensitive adhesive composition for a patch, comprising a compound (D) and a water (B) content of 5 to 30% by mass.
2. When the repeating unit has the general formula (1) or (2)

(The meanings of the symbols in the formula are the same as described in the above item 1.)
2. The pressure-sensitive adhesive composition for a patch according to the above item 1, wherein the (meth) acrylic acid-based polymer (A) has a 0.2% by mass aqueous solution viscosity of 400 mPa · s or more.
3. 2. The adhesive composition for a patch according to the above item 1, wherein the polyhydric alcohol is a trihydric or higher alcohol.
4. 4. The adhesive composition for a patch according to the above item 3, wherein the polyhydric alcohol is glycerin.
5. 2. The pressure-sensitive adhesive composition for patches as described in 1 above, wherein the content of the polyhydric alcohol is 40 to 94.5% by mass based on the total amount of the composition.
6. 2. The adhesive composition for a patch according to the above item 1, wherein a water-soluble aluminum compound and alumina / magnesium hydroxide are used in combination as the aluminum compound.
7. 2. The pressure-sensitive adhesive composition for a patch according to the above item 1, wherein the content of the aluminum compound is 0.01 to 20% by mass relative to the total amount of the composition.
8. 2. The adhesive composition for a patch according to the above item 1, further comprising a polymer compound (E) having a high affinity for polyhydric alcohol.
9. The pressure-sensitive adhesive composition for a patch according to the above item 8, wherein the polymer compound (E) having a high affinity for the polyhydric alcohol is at least one selected from a carboxyvinyl polymer and an N-vinylacetamide-sodium acrylate copolymer. .
10. The pressure-sensitive adhesive composition for a patch according to the above item 8 or 9, wherein the content of the polymer compound having a high affinity for the polyhydric alcohol is 0.01 to 20% by mass relative to the total amount of the composition.
11. The pressure-sensitive adhesive composition for a patch according to any one of the above items 1 to 10, which contains diclofenac sodium as a medicinal ingredient.
12. 11. The adhesive composition for a patch according to the above 1 to 10, which comprises capsaicin as a medicinal ingredient.
13. When the repeating unit has the general formula (1) or (2)

(The meanings of the symbols in the formula are the same as described in the above item 1.)
Where (1) / (2) = 100/0 to 90/10 (molar ratio), (meth) acrylic acid-based polymer (A), water (B), polyhydric alcohol (C), aluminum A pressure-sensitive adhesive composition for a patch containing the compound (D) as an essential component, optionally containing a polymer compound (E) having a high affinity for a polyhydric alcohol, and having a water (B) content of 5 to 30% by mass. In a method for producing a product, a (meth) acrylic acid-based polymer (A) and a water (B) solution of a polyhydric alcohol (C) are mixed at a water concentration of 50% or more based on their total mass, and then the remaining components are mixed. A patch characterized by adding and mixing (the remaining polyhydric alcohol (C), aluminum compound (D) and, if desired, polymer compound (E)) and adjusting the water concentration to 5 to 30%. Method for producing pressure-sensitive adhesive composition for use.

Embodiment of the Invention

Hereinafter, the present invention will be described in detail.
The present inventors have observed the solubility of polyacrylic acid, partially neutralized polyacrylic acid (acrylic acid-acrylate copolymer) and polyacrylate in a high-concentration polyhydric alcohol aqueous solution. Polyacrylic acid was dissolved in a high-concentration polyhydric alcohol aqueous solution, but the solution itself was slightly cloudy because the polymer itself had high cohesiveness. For the partially neutralized polyacrylic acid, the solubility was examined by changing the copolymerization ratio of acrylic acid and acrylate, but as the content of acrylic acid, which has a high affinity for alcohol, increased, the solubility increased. showed that. However, surprisingly, it was found that when the content of acrylic acid was 10 mol% or less, it showed good solubility in a high-concentration polyhydric alcohol aqueous solution, and the present invention was completed. It is unknown why the acrylate-rich one showed high solubility, but the presence of even a small amount of water dissociates the salt, i.e., due to the presence of a large amount of carboxylate, This is probably due to the increased affinity. On the other hand, when the content of acrylic acid or methacrylic acid (hereinafter, “acrylic acid or methacrylic acid” is abbreviated as “(meth) acrylic acid”), the amount of free carboxyl groups in the polymer molecular chain increases, so that the polymer Are aggregated (condensed), so that dissociation of the salt is suppressed, and as a result, the amount of carboxylate is considered to be reduced.

  In addition, since the (meth) acrylic acid-based polymer as the base material is water-soluble, the hydrophilicity of the pressure-sensitive adhesive layer is improved, and it absorbs water secreted on the skin surface, so that the adhesiveness of the patch to the skin is maintained. Satisfactory pharmacological effects are sufficiently obtained, and an equilibrium state is established with the external water vapor, so that skin unevenness and rash can be prevented.

  Since the pressure-sensitive adhesive for patches obtained in the present invention has excellent properties, it can be applied to various uses as described below.

(I) Pharmaceuticals: patches such as transdermal preparations, transmucosal preparations, etc.
(II) Medical equipment: Cooling agent for affected area during fever, wound healing agent, pad for treatment, liquid absorbing agent for surgery, burn healing agent, etc.
(III) Cosmetics, quasi-drugs: packs, suntan products, face masks, acne products, etc.

  The adhesive composition for a patch of the present invention comprises a (meth) acrylic acid-based polymer (component A), water (component B), a polyhydric alcohol (component C) and an aluminum compound (component D) as essential components. And the amount of water is substantially as low as 5 to 30% by mass.

  The (meth) acrylic acid-based polymer (component A) used in the present invention is used in the range of 0.5 to 30% by mass (hereinafter simply referred to as%) based on the total amount of components A to C. It is more preferable that the content be in the range of 2% to 20%. If it is less than 0.5%, syneresis liquid is generated from the gel body, resulting in a non-uniform adhesive layer. If it exceeds 30%, the viscosity of the sol at the time of molding rises, making molding and mixing of other components difficult. It becomes.

（式中、Ｒ¹およびＲ²は、各々独立して、水素原子またはメチル基を表わし、ＭはＮＨ₄ ⁺またはアルカリ金属を表わす。）
で示され、（１）／（２）＝１００／０〜９０／１０（モル比）である（メタ）アクリル酸系重合体としては、具体的には、
（１）アクリル酸またはメタアクリル酸のナトリウム塩、カリウム塩のようなアルカリ金属塩、アンモニウム塩等の単独重合体、
（２）アクリル酸またはメタアクリル酸のナトリウム塩、カリウム塩のようなアルカリ金属塩、アンモニウム塩等とアクリル酸との共重合体、
（３）アクリル酸またはメタアクリル酸のナトリウム塩、カリウム塩のようなアルカリ金属塩、アンモニウム塩等とメタアクリル酸との共重合体等をあげることができる。
なお、上記（メタ）アクリル酸系重合体（Ａ）は、その０．２質量％水溶液の粘度が４００ｍＰａ・ｓ以上であることが好ましい。粘度が４００ｍＰａ・ｓ未満であるとゲル体から離漿液が生成し、不均一な粘着層となる。
また、本発明の貼付剤用粘着剤組成物には、前記（Ａ）成分の（メタ）アクリル酸系重合体の他に、前記（１）／（２）のモル比の範囲を超える（すなわち（メタ）アクリル酸のモル比が１０モル％を超える）（メタ）アクリル酸系重合体を、前記（Ａ）成分の添加量を超えない範囲で、かつ組成物の全質量に対して５％を超えない範囲で添加することもできる。 The repeating units constituting the component (A) are represented by the general formulas (1) and (2)

(In the formula, R ¹ and R ² each independently represent a hydrogen atom or a methyl group, and M represents NH ₄ ⁺ or an alkali metal.)
And (1) / (2) = 100/0 to 90/10 (molar ratio), specifically, as the (meth) acrylic acid-based polymer,
(1) A homopolymer such as an alkali metal salt such as a sodium salt or a potassium salt of acrylic acid or methacrylic acid, or an ammonium salt;
(2) a copolymer of acrylic acid or methacrylic acid with an alkali metal salt such as a sodium salt or a potassium salt, an ammonium salt or the like, and acrylic acid;
(3) Copolymers of methacrylic acid with alkali metal salts such as sodium or potassium salts of acrylic acid or methacrylic acid, ammonium salts and the like.
The (meth) acrylic acid-based polymer (A) preferably has a 0.2% by mass aqueous solution having a viscosity of 400 mPa · s or more. If the viscosity is less than 400 mPa · s, a syneresis liquid is generated from the gel body, resulting in an uneven adhesive layer.
In the pressure-sensitive adhesive composition for a patch of the present invention, in addition to the (meth) acrylic acid-based polymer of the component (A), the molar ratio of the above (1) / (2) is exceeded (ie, The (meth) acrylic acid-based polymer is added in an amount not exceeding the amount of the component (A) and not more than 5% based on the total mass of the composition. Can be added in a range not exceeding.

  Water is added to increase the solubility of the (meth) acrylic acid-based polymer and to increase the viscosity, and the added amount is 5 to 30%. When the content is less than 5%, the solubility of the (meth) acrylic acid-based polymer in polyhydric alcohol is deteriorated, and the thickening effect is reduced, so that the polymer remains on release paper or on the surface of the applied skin. The phenomenon of “adhesive residue” and the phenomenon of so-called “through-through” in which the adhesive for a patch slips out of the support may occur. On the other hand, if the content is more than 30%, the solubility of the drug in the composition becomes poor, and the diffusion rate of the drug is reduced, and as a result, the absorbability to the skin is reduced.

  The polyhydric alcohol (C) is added for the purpose of increasing the solubility and activity of the drug in the adhesive for patch and improving the transferability to the skin. Examples of the polyhydric alcohol include ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol, triethylene glycol, 1,4-butylene glycol (dihydric alcohol), glycerin, trioxyisobutane (trihydric alcohol), erythrit, Examples include, but are not limited to, pentaerythritol (tetrahydric alcohol), xylit, adnit (pentahydric alcohol), allodulcit, sorbitol, sorbitol solution, mannitol (hexhydric alcohol), polyglycerin, dipropylene glycol, and the like. Among them, glycerin is particularly preferred in view of its safety and affinity with the (meth) acrylic acid-based polymer. Polyhydric alcohols may be used alone or in combination of two or more.

The polyhydric alcohol is added in the range of 40 to 94.5%, more preferably 70 to 90%, based on the total amount of the composition. If the added amount is less than 40%, the solubility of the drug in the base becomes insufficient, resulting in a decrease in absorbability to the skin.
If it exceeds 94.5%, the effect of increasing the viscosity of the polymer of the (meth) acrylic acid salt is difficult to be exhibited, and it is difficult to obtain a sufficient shape-retaining property of the adhesive layer.

  Solvents other than polyhydric alcohols can be added as desired. These solvents include monohydric alcohols such as methanol, ethanol, propanol, benzyl alcohol, phenethyl alcohol, isopropyl alcohol, isobutyl alcohol, hexyl alcohol, 2-ethylhexanol, cyclohexanol, octyl alcohol, butanol, pentanol, acetone, In addition to water-miscible organic solvents such as ketones such as methyl ethyl ketone, cellosolve, dioxane, dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide, water-immiscible organic solvents such as ethyl acetate and crotamiton are exemplified.

  An aluminum compound (D) is added as a cross-linking agent to the pressure-sensitive adhesive for patch of the present invention in order to maintain the shape retention of the gel and to prevent "paste residue".

  These aluminum compounds (D) are added in the range of 0.01 to 20%, more preferably in the range of 0.1 to 10%, based on the total amount of the composition. If the added amount is less than 0.01%, the crosslinking becomes insufficient and stringing occurs in the base. If it exceeds 20%, the gel becomes too hard, and the adhesiveness of the composition becomes poor. The adhesiveness can be freely controlled by changing the amount of the aluminum compound.

  Examples of the aluminum compound include aluminum chloride, potassium aluminium, ammonium aluminium, aluminum nitrate, aluminum sulfate, EDTA-aluminum, aluminum hydroxide / sodium hydrogen carbonate coprecipitate (for example, “Kumlite” manufactured by Kyowa Chemical Industry Co., Ltd.) ), Synthetic aluminum silicate, aluminum stearate, aluminum allantoinate, synthetic hydrotalcite (for example, "Alkamac", "Alkamizer", "Kyoward", etc., manufactured by Kyowa Chemical Industry Co., Ltd.), alumina hydroxide Magnesium (e.g., "Sanamin" manufactured by Kyowa Chemical Industry Co., Ltd.), aluminum hydroxide (e.g., "dried aluminum hydroxide gel S-100" manufactured by Kyowa Chemical Industry Co., Ltd.), aluminum acetate, dihydroxyaluminum aminoacetate (For example, Kyowa Manabu Industries Co., Ltd. "Gurishinaru", etc.), kaolin, magnesium aluminometasilicate (e.g., Fuji Chemical Industry Co., Ltd., "Neusilin"), and magnesium aluminate silicate acid. These aluminum compounds may be water-soluble or hardly soluble. One or more of these aluminum compounds can be used. Of these aluminum compounds, the water-soluble one and alumina hydroxide / magnesium hydroxide are used in combination to promote the initial crosslinking in the former and the latter crosslinking in the latter to provide an adhesive layer having excellent shape retention in a short time. Can be obtained.

  Crosslinking agents other than aluminum compounds can also be added. Examples thereof include inorganic salts of calcium, tin, iron, magnesium, manganese, zinc, barium and the like (for example, calcium chloride, magnesium chloride, iron ash, ferric sulfate, magnesium sulfate, EDTA-calcium, EDTA-magnesium). , Stannous chloride, calcium carbonate, calcium phosphate, calcium hydrogen phosphate, magnesium carbonate, barium sulfate, magnesium silicate, magnesium stearate, magnesium citrate), hydroxide (for example, calcium hydroxide, barium hydroxide, water) Magnesium oxide (e.g., "Kisuma" manufactured by Kyowa Chemical Industry Co., Ltd.), ferric hydroxide, stannous hydroxide, etc.), oxides (e.g., magnesium oxide (e.g., manufactured by Kyowa Chemical Industry Co., Ltd.) Kyowa Mag "," Mag Salat "etc.)), formaldehyde, ethylene glycol Call diglycidyl ether, glycerin diglycidyl ether, polyethylene glycol diglycidyl ether, propylene glycol diglycidyl ether, and epoxy compounds such as polypropylene glycol diglycidyl ether. One or more of these crosslinking agents can be used.

  Further, as a speed controlling agent for the crosslinking reaction, metal ions such as tartaric acid, citric acid, lactic acid, glycolic acid, malic acid, salicylic acid, fumaric acid, methanesulfonic acid, maleic acid, acetic acid, sodium EDTA-2, urea, triethylamine and ammonia Organic acids, organic acid salts, organic bases and the like having chelating or coordinating ability, as well as inorganic acids such as hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid and hydrobromic acid can be used.

  A polymer having a high affinity for polyhydric alcohol can be added to the adhesive for patch of the present invention for the purpose of improving the retention of polyhydric alcohol. These polymers include N-vinylacetamide copolymers such as polyvinylpyrrolidone, carboxyvinyl polymer which is a cross-linked polyacrylic acid, vinylpyrrolidone-ethyl acrylate copolymer, and N-vinylacetamide-sodium acrylate copolymer. Polymers, N-vinylacetamide homopolymer, polyvinyl sulfonic acid, N-vinylacetamide crosslinked product, polyitaconic acid, hydroxypropylcellulose, hydroxypropylmethylcellulose and the like can be mentioned. Among these, those crosslinked by a crosslinking agent added to crosslink the polymer of (meth) acrylate are particularly preferred. Specifically, carboxyvinyl polymer, N-vinylacetamide-sodium acrylate copolymer, polyvinyl sulfonic acid and the like are preferable, but carboxyvinyl polymer and N-vinylacetamide-sodium acrylate copolymer are preferable from the viewpoint of retention ability. Most preferred. In the N-vinylacetamide-sodium acrylate copolymer, the mass ratio of N-vinylacetamide to sodium acrylate is preferably in the range of 99.9 to 60: 0.1 to 40.

  These polymers are added in the range of 0.1 to 20% based on the total amount of the composition, and more preferably in the range of 1 to 10%. When the addition amount is less than 0.1%, the polyhydric alcohol does not have sufficient holding power, and when it exceeds 20%, the adhesive layer becomes hard, and the feeling of close contact with the skin is deteriorated. Is inferior.

There are many drugs that can be administered using the gel of the present invention. Specific examples are given below, but the present invention is not limited to these.
(A) corticosteroids: hydrocortisone, prednisone, beclomethasone propionate, flumethasone, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol propionate, etc.
(B) Antiphlogistic analgesics: salicylic acid, glycol salicylate, methyl salicylate, 1-menthol, camphor, sulindac, sodium trimethine, naproxen, fenbufen, piroxicam, triamcinolone, hydrocortisone acetate, indomethacin, ketoprofen, acetaminophen, mefenamic acid, flufenam Acid, ibufenac, loxoprofen, tiaprofen, pranoprofen, fenprofen, diclofenac, diclofenac sodium, alclofenac, lornoxicam, planoprofen, oxyphenbutazone, ibuprofen, ferpinac, ketronac, vermoprofen, napmeton, naproxen, Flurbiprofen, fluocinonide, clobetasol propionate, COX- Inhibitors (nimesulide, meloxicam, etodolac, celecoxib, and rofecoxib) and the like,

(C) Antifungal agents: clotrimazole, tolnaftate, econazole nitrate, omoconazole nitrate, thioconazole nitrate, ketoconazole nitrate, miconazole nitrate, isoconazole nitrate, tolnaftate, thioconazole nitrate, sulconazole nitrate, pyrrolnitrin, pimafucin, undecylenic acid, salicylic acid, Siccanin, nystatin, nornaphthate, exalamide, phenyl iodoundecinoate, thiantol, ciclopirox olamine, haloprosin, tricomycin, variotin, pentamycin, amphotericin B, etc.
(D) Antihistamines: antibiotics such as tetracycline hydrochloride, diphenhydramine hydrochloride, chlorpheniramine, diphenylimidazole, chloramphenicol, diphenhydramine, chlorpheniramine maleate, etc.
(E) hypnotic sedatives: phenobarbital, amobarbital, cyclobarbital, lorazepam, haloperidol, etc.

(F) tranquilizers: fluphenazine, theorydazine, diazepam, flunittoazepam, chlorpromazine, etc.
(G) Antihypertensive agents: clonidine, clinidine hydrochloride, pindolol, propranol, propranol hydrochloride, bupranolol, indenolol, bucmorol, nifedipine, etc.
(H) antihypertensive diuretics: hydrothiazide, bendrofluthiazide, cyclopentiazide, etc.
(I) antibiotics: penicillin, tetracycline, oxytetracycline, fradiomycin sulfate, erythromycin, chloramphenicol, etc.
(J) anesthetics: lidocaine, benzocaine, ethyl aminobenzoate, dibucaine, etc.

(K) antibacterial substances: benzalkonium chloride, nitrofurazone, nystatin, acetosulfamine, clotrimazole, etc.
(L) Vitamin preparation: Vitamin A, ergocalciferol, cholecalciferol, octtiamine, riboflavin butyrate, etc.
(M) antiepileptic drugs: nitrazepam, mepropamate, clonazepam, etc.
(N) coronary vasodilators: nitroglycerin, nitroglycol, isosorbidinylate, erythritol tetranitrate, pentaerythritol tetranitrate, propillyl nitrate, etc.
(O) antihistamines: for example, diphenhydramine hydrochloride, chlorpheniramine, diphenylimidazole, etc.

(P) Antitussives: dextromethorphan, terbutamine, ephedrine, ephedrine hydrochloride, etc.
(Q) Sex hormones: progesterone, estradiol, etc.
(R) antidepressants: doxepin, etc.
(S) therapeutic agent for angina pectoris: antiperspirants such as diethylamide and camphor, nitroglycerin, isosorbide dinitrate, etc.
(T) narcotic analgesics: morphine hydrochloride, ethyl morphine hydrochloride, morphine sulfate, cocaine hydrochloride, pethidine hydrochloride, codeine phosphate, dihydrocodeine phosphate, fentanyl citrate, sufentanil, meperidine hydrochloride, etc.
(U) Herbal medicines: oak, spruce, onji, gejutsu, chamomile, karonin, licorice, kikyo, kyounin, gooh, goshi, honey, psycho, saishin, shizenshi, shoma, senega, sojutsu, souhakuhi, choji, chimpanzee, tokonji , Frog, bakkumondou, hange, beak jujutsu, hyos, bouhou, ephedra, pepper extract, etc.

(V) Others: In addition to 5-fluorouracil, dihydroergotamine, fentanyl, desmopressin, digoxin, metocloprside, domperide, scopolamine, scopolamine hydrobromide, veterinary drugs, sleeping pills, circulatory drugs, cerebral metabolism enhancers , Fungicides, enzyme preparations, enzyme inhibitors, biopharmaceuticals (polypeptides), keratosis treatment drugs, narcotics, antineoplastic agents, general anesthetics, anxiolytics, asthma and nasal allergies, antiparkinson drugs, chemistry Therapeutic agents, anthelmintics, antiprotozoal agents, hemostatic agents, cardiotonic agents, stimulants / stimulants, addictive agents, herbal medicines, radiopharmaceuticals, genitourinary and anal agents, hypoglycemic agents, anti-ulcer agents, hair agents , Sequestering agents, antiperspirants, tranquilizers, antimimic agents, antirheumatic, antigout agents and anticoagulants.
The above drugs can be used in combination of two or more as necessary. The compounding ratio of the drug is preferably adjusted to 0.01 to 30% by mass, more preferably 2 to 20% by mass, based on the total mass of the adhesive for patch.

Among the above drugs, it is known that, for example, capsaicin contained in a pepper extract increases irritation to the skin when a large amount of water coexists. ADVANTAGE OF THE INVENTION According to this invention, since the water content of the adhesive for patches can be reduced, the hot-type patch containing capsaicin containing little skin irritation can be produced.
Furthermore, in recent years, VR1 of the receptor for capsaicin, a hot ingredient of pepper, is activated by heat or an increase in acidity of 43 ° C. or higher instead of capsaicin, and acts to transmit heat and pain stimuli to the brain. (Mitsuko Numazaki et al .: Ayumi of Medicine, Vol. 13, 1071-1075 (2002)). Utilizing this knowledge, research using capsaicin as an analgesic is progressing. That is, by using the pressure-sensitive adhesive composition of the present invention, a capsaicin-containing patch (analgesic) with low irritation can be obtained. This patch is particularly preferably used for postherpetic neuralgia. In this postherpetic neuralgia, pain occurs along the nerve and the pain is present in a band. Therefore, the following forms can be considered as a patch. For example, it is formed into a roll shape having a width of 1 to 10 cm, and cut and pasted at the length of the place where pain occurs. Examples of the small size include those in which a circular patch having a diameter of 1 to 10 cm or a square or small rectangular patch having a piece of 1 to 10 cm is arranged side by side at a place where pain occurs, and the like.

  In the pressure-sensitive adhesive for patches of the present invention, the drug can be included in the solution stage (or gel suspension stage) or after aging for the crosslinking reaction. The preferred method depends on the physical properties of the drug, the site of administration and the desired release rate.

  In addition, an auxiliary agent for promoting the absorption of these drugs can be added. Such adjuvants include, for example, ethyl alcohol, isopropyl alcohol, n-butanol, 1,3-butanediol, propylene glycol, polyethylene glycol # 400, glycerin, crotamiton, benzyl alcohol, phenylethyl alcohol, propylene carbonate, hexyldecadecane Nol, propanol, salicylic acid, allantoin, dimethyl sulfoxide, dimethyl acetamide, dimethyl formamide, diisopropyl adipate, diethyl sebacate, ethyl laurate, lanolin, Aison, 1-geranylazacycloheptan-2-one (GACH), fatty acid dialkylol Amide, salicylic acid, salicylic acid derivatives, keratin softeners such as urea and sulfur, humectants such as pyrrolidone carboxylic acid, propylene glycol monooxide Surfactants such as polyoxyethylene sorbitan monostearate, sorbitan monostearate and glycerin monostearate; esters such as isopropyl myristate and diethyl sebacate; and higher alcohols such as oleyl alcohol, stearyl alcohol and lauryl alcohol. , Stearic acid, hexanoic acid, nonanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, oleic acid, linoleic acid, etc. , Terpene compounds such as carpeol and surfactants, allantoin, dimethylsulfoxide, dimethylacetamide, dimethylformamide, diisopropyladipate, diethyl Auxiliaries such as bakate, ethyl laurate, lanolin, and aison, and other cooling agents such as menthol and camphor if necessary, almond oil, olive oil, camellia oil, persic oil, peppermint oil, sesame oil, soybean oil, and mink oil , Cottonseed oil, corn oil, safflower oil, coconut oil, eucalyptus oil, castor oil, liquid paraffin, oil components such as petrolatum, squalene, squalane, lanolin, gelling agents such as carboxyvinyl polymers, neutralization of diisopropanolamine, etc. One or more types of agents can be blended. In view of skin irritation and the like, the amount of these components is preferably 0.1 to 5 parts by mass with respect to 100 parts by mass of the drug.

  In the composition used in the present invention, in order to express more of its properties, or to improve the processability and moldability and quality, to improve the dispersibility and stability of the drug in the gel body, gel The additives selected according to the purpose can be further arbitrarily added to such an extent that the performance of the above is not impaired. The following are specific examples of the additives in that case.

(1) Wetting agents: glycerin, propylene glycol, sorbit, 1,3-butylene glycol, dl-pyrrolidone carboxylic acid, sodium lactate and the like.
(2) Astringents: citric acid, tartaric acid, lactic acid, aluminum chloride, aluminum sulfate, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, aluminum phenolsulfonic acid, zinc paraphenolsulfonate, zinc sulfate, aluminum chlorohydroxide and the like.
(3) Moisturizing agents: polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerin, polyethylene glycol, dipropylene glycol, NMF components such as sodium lactate, hyaluronic acid, collagen, mucopoly Water-soluble polymers such as sugars and chondroitin sulfate;

(4) Thickeners: gum arabic, gum tragacanth, locust bean gum, guar gum, echo gum, karaya gum, agar, starch, carrageenan, alginic acid, alginates (eg, sodium alginate), propylene glycol alginate, dextran, dextrin, amylose, gelatin, Natural polymers such as collagen, pullulan, pectin, amylopectin, sodium amylopectin semiglycolate, chitin, albumin, casein, polyglutamic acid, polyaspartic acid, methylcellulose, ethylcellulose, propylcellulose, ethylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, Hydroxypropyl methylcellulose, carboxymethyl starch, alkali metal carboxy Semi-synthetic polymers such as chill cellulose, alkali metal cellulose sulfate, cellulose graft polymer, cross-linked gelatin, cellulose acetate phthalate, starch-acrylic acid graft polymerization, phthalic anhydride-modified gelatin, succinic acid-modified gelatin, polyvinyl alcohol, and polyvinyl Pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, vinylpyrrolidone-ethyl acrylate copolymer, vinylpyrrolidone-styrene copolymer, vinylpyrrolidone-vinyl acetate copolymer, vinyl acetate- (meth) acrylic acid copolymer, polyvinyl N-vinylacetamide copolymers such as acetate-crotonic acid copolymer, N-vinylacetamide-sodium acrylate copolymer, polyvinyl sulfonic acid, crosslinked N-vinylacetamide Polyitaconic acid, polyhydroxyethyl acrylate, polyacrylamide, styrene - maleic acid anhydride copolymer, acrylamide - polymers of synthesis such as acrylic acid copolymer.

(5) Tackifier: Each tackifier such as silicone rubber, polyisobrengon, styrene-block copolymer rubber, acrylic rubber, natural rubber and the like.
(6) Antipruritics: camphor, thymol, menthol, polyoxyethylene lauryl ether, antihistamines, ethyl aminobenzoate, and the like.
(7) Exfoliating agents for keratin: sulfur, thioxolone, selenium sulfide, salicylic acid, resorcin and the like.
(8) Ingestion prevention substances: pepper powder, pepper essence, etc.
(9) Powder raw materials: montmorillolate, silicic acid anhydride, limestone, carbon black, diatomaceous earth, red iron oxide, calcium carbonate, hydrotalcite, talc, glass, kaolin, bentonite, metal soap, aerosil, mica titanium, oxychloride Bismuth, fish scale foil, zinc white, titanium dioxide, etc.

(10) Oily raw materials: almond oil, olive oil, hardened oil, camellia oil, castor oil, mokurou oil, coconut oil, beeswax, whale wax, lanolin, carnauba wax, candelilla wax, liquid paraffin, vaseline, microcrystalline wax, ceresin, Squalene, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, octyldodecanol, cholesterol, hexyldecanol, waitosterol, cetyl lactate, isopropyl myristate, laurin Hexyl acid, myristyl myristate, isopropyl palmitate, octyl dodecanol myristate, butyl stearate, cocoa oil, jojoba oil, grape seed oil, a Kad oil, mink oil, egg yolk oil, ceresin wax, paraffin wax, behenic acid, isopropyl adipate, octyldodecyl myristate, octyldodecyl oleate, cholesterol oleate.

(11) Surfactant: lauryl sulfate, polyoxyethylene alkyl ether sulfate, alkylbenzene sulfonate, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl phenyl ether phosphate, N-acyl amino acid salt, stearic acid Anionic surfactants such as sodium, potassium palmitate, sodium cetyl sulfate, sodium lauryl sulfate, triethanolamine palmitate, sodium polyoxyethylene lauryl phosphate, sodium acylglutamate, surfactin, benzalkonium chloride, benzethonium chloride, chloride Cationic surfactants such as stearyltrimethylammonium, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, alkyldihydrochloride Amphoteric surfactants such as minoethylglycine, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetate betaine, lecithin, polyol fatty acid ester, glyceryl monostearate, lipophilic monoolein Glycerin acid, ethylene glycol monostearate, propylene glycol monostearate, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenol ether, polyoxyethylene sorbitol fatty acid ester , N-acyl amino acid ester, sucrose fatty acid ester, fatty acid alkylolamide, polyoxyethylenated sterol Polyoxyethylenated lanolin, nonionic surfactants such as polyoxyethylene hydrogenated castor oil and the like.

(12) Colorant: yellow iron oxide, red iron oxide, black iron oxide, ultramarine, carbon black, chromium hydroxide, chromium oxide, tar dye, lake, red No. 2, red No. 3, red No. 102, red No. 201, yellow No. 4, Yellow No. 5, Blue No. 1, Blue No. 2, etc.
(13) Flavors: poppy oil, orange oil, pepper oil, jasmine oil, cedar oil, shobu oil, terpine oil, orange flower oil, rose oil, eucalyptus oil, lime oil, lemon oil, Japanese peppermint oil, rosemary oil Vegetable flavors such as musk, leybium, karikou, Ryuzenkou, hydrocarbon flavors such as bromostyrol, pinene, limonene, alcohol flavors such as benzyl alcohol, l-menthol, ethyl acetate, methyl salicylate, etc. Ester-based flavors, benzaldehyde, salicylaldehyde, etc., aldehyde-based flavors, camphor, muscone, musk ketone, ketone-based flavors such as l-mentone, ether-based flavors such as safrole, phenol-based flavors such as thymol, lactone Related flavors, acid flavors such as phenylacetic acid, nitrogen compounds such as indole Perfumes and the like.

(14) UV blocking agents: ASL-24, Cyasorb UV-9, benzophenones such as Uvinul M-40, benzoic acids such as Salol, azoles such as Tinuvin P, nitriles such as Uvinul N-35, Ancor UA Urea-based, such as Neo Heliopan Give tan F, 2-hydroxy-4-methoxybenzophenone, octyldimethylparaaminobenzoate, para-amino acid-based such as ethylhexylparamethoxycinnamate, salicylic acid-based, benzofuran-based, coumarin-based, and azole-based.

(15) Preservative antiseptics: acids such as benzoic acid, salicylic acid, dehydroacetic acid, sorbic acid, boric acid and salts thereof, phenol, chlorocresol, chlorxylenol, isopropylmethylphenol, resorcinol, orthophenylphenol, paraoxybenzoate, Phenols such as phenoxyethanol, thymol, hinokitiol, thioxolone, halogenated bisphenols such as hexachlorophene, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, trichlorocarbanilide, halocarban, udesilenic acid monoethanolamide, etc. Amide compounds, quaternary ammonium compounds such as benzalkonium chloride, alkylisoquinolinium bromide, benzethonium chloride and cetylpyridinium chloride, lauryldi (aminoethyl A) Amphoteric surfactants such as glycine, 2-pyridinethiol-1-oxide zinc salt, gluconic acid, chlorhexidine, thiram, N-trichloromethylthio-4-cyclohexene-1.2-dicarboximide, chlorobutanol and the like.

(16) Antioxidants: nordihydroguaiaretinic acid, guaiac butter, propyl gallate, butylhydroxyanisole, dibutylhydroxytoluene (BHT), tocopherol (vitamin E), 2,2′-methylenebis (4-methyl-6) -T-butyl) phenol and the like.
(17) Chelating agents: edetate, pyrophosphate, hexametaphosphate, citric acid, tartaric acid, gluconic acid and the like.
(18) UV scattering agents: titanium oxide, kaolin, talc and the like.

(19) pH adjuster: sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonia, aqueous ammonia, triethanolamine, dimethylamine, diethylamine, trimethylamine, triethylamine, triisopropanolamine, trisodium phosphate, Alkali metal hydroxides such as disodium hydrogen phosphate, dipotassium hydrogen phosphate, monoethanolamine, diethanolamine, diisopropanolamine, polyethanolamine, etc., alkaline earth metal hydroxides, primary, secondary or secondary Alkalis such as tertiary alkylamines, or primary, secondary or tertiary alkanolamines; and acids such as citric acid, tartaric acid, lactic acid, glycolic acid, hydrochloric acid, nitric acid, malic acid, phosphoric acid, etc. Indicates acidic or alkaline Polymers are also used, for example, alginic acid, polyglutamic acid, polyaspartic acid, starch-acrylic acid graft polymer, polyacrylic acid, vinyl acetate-crotonic acid copolymer, vinyl acetate- (meth) acrylic acid copolymer, acetic acid Vinyl-crotonic acid copolymer, polyvinyl sulfonic acid, polyitaconic acid, styrene-maleic anhydride copolymer, acrylamide-acrylic acid copolymer and the like.

  In addition, stabilizers, fillers, preservatives, plasticizers, softeners, deterioration inhibitors and the like can be added. These additives are arbitrarily added within a range that does not affect the properties of the resulting adhesive for patches.

  In the present invention, the adhesive for patch is directly mixed with various raw materials and then poured into a suitable mold in a sol state, and then crosslinked and molded, or the crosslinked gel is directly molded with a suitable molding machine, tableting machine or the like. It is used to prepare various molded products. The mixing of the raw materials can be performed by appropriately selecting and using, for example, a kneader, a co-kneader, a kneader ruder, an ajihomo mixer, a planetary mixer, a double planetary mixer, and the like.

  At this time, the (meth) acrylic acid-based polymer (A) and the water (B) solution of the polyhydric alcohol (C) are mixed at a water concentration of 50% or more based on their total mass, and then the remaining components (the remaining (Meth) acrylic acid system by adding and mixing a polyhydric alcohol (C), an aluminum compound (D) and, if desired, a polymer compound (E)) and adjusting the water concentration to 5 to 30%. The dissolution of the polymer becomes easy, and the adhesive for a patch of the present invention can be produced in a shorter time.

  For example, 5 g of sodium polyacrylate is well dispersed in 45 g of glycerin, and kneaded while gradually adding the dispersion to 50 g of water. Then, since the water concentration at this point is 50%, the polymer dissolves in a short time, and the system tends to be uniform. After confirming that the polymer has been uniformly dissolved, kneading is performed while adding the remaining 100 g of glycerin, so that the final concentration of water in the composition can be 25%. The feature of this method is that once the polymer has been dissolved, the polymer does not precipitate out and remains dissolved even when polyhydric alcohol is added thereafter.

  To make the adhesive for adhesive patch into a sheet, paper, wood, metal, glass fiber, cloth (nel, woven fabric, non-woven fabric, etc.), synthetic resin (polyurethane, ethylene-vinyl acetate copolymer, polyvinyl chloride, polyester ( For example, polyethylene terephthalate), polyolefins (eg, polyethylene, polypropylene, etc.), polyamides (eg, nylon 6, nylon 66, etc.), polyvinylidene chloride, polytetrafluoroethylene, etc., metal foils such as aluminum, rubber or cellulose derivatives, and An appropriate amount of the adhesive for a patch may be applied to one or both sides of a support such as a molded product such as a laminated film with a plastic film, a sheet (foil), or a tape. To make it easier to store the adhesive, apply it to the surface where the adhesive for patch is applied. Affix a release sheet treated with silicon or other suitable method, or treat the surface not coated with the adhesive for patch with silicone or other suitable method to obtain a release surface. Desirably, the sheet is rolled or overlapped so as to overlap with the uncoated surface, and the release sheet may be a polyethylene film, a polypropylene film, release paper, cellophane, polyvinyl chloride, polyester, or the like.

  Next, usefulness of the present invention will be described with reference to examples, but the present invention is not limited thereto. In addition, a part shows a mass part.

Example 1
[Ingredients and proportions]
Sodium polyacrylate (viscosity ^* 560 mPa · s) 2 parts Glycerin 75.9 parts Aluminum sulfate 1 part Alumina magnesium hydroxide 0.5 parts Water 18.975 parts Sodium hydroxide 0.625 parts Carboxyvinyl polymer 1 part * Viscosity Is a value obtained by measuring a 0.2% by mass aqueous solution with a B-type viscometer (20 ° C., rotor No. 2, 30 rpm, 30 minutes) (the same applies hereinafter).

[Prescription]
To a mixture of water (12.5 parts) and aluminum sulfate (1 part), add a dispersion of sodium polyacrylate ("Biscomate F480SS": Showa Denko KK) (2 parts) and glycerin (10 parts) and mix. did. When the polymer begins to dissolve and thickens, glycerin (65.9 parts) and carboxyvinyl polymer (“AQUPEC HV-504E”, manufactured by Sumitomo Seika Co., Ltd.) (1 part) and magnesium alumina hydroxide (“Sanamin”): A mixed solution with Kyowa Chemical Industry Co., Ltd. (0.5 parts) was added, and finally a solution of sodium hydroxide (0.625 parts) and water (6.475 parts) was gradually added and kneaded until uniform.
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and stretched by touching the gel with a finger, and had a strong repulsive force.

Example 2:
[Ingredients and proportions]
Acrylic acid / sodium acrylate (10/90 (molar ratio)) copolymer (viscosity: 401 mPa · s) 5.5 parts Glycerin 75.86 parts Capsaicin 0.5 parts Aluminum sulfate 1.6 parts Purified water 14.54 parts N-vinylacetamide / sodium acrylate
(90/10 (mass ratio)) copolymer 2 parts

[Prescription]
Acrylic acid / sodium acrylate copolymer (5.5 parts), glycerin (12.94 parts), capsaicin (0.5 parts) and N-vinylacetamide / acrylic acid were added to a mixture of aluminum sulfate (1.6 parts) and purified water (14.54 parts). A mixed solution of the sodium copolymer (2 parts) was gradually added, and the mixture became uniform. Then, glycerin (62.92 parts) was gradually added and kneaded until uniform.
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and stretched by touching the gel with a finger, and had a strong repulsive force.

Example 3
[Ingredients and proportions]
Sodium polyacrylate (viscosity 675 mPa · s) 4 parts Glycerin 57.9 parts Propylene glycol 15 parts Aluminum sulfate 1 part Purified water 18.6 parts Carboxyvinyl polymer 2 parts Diclofenac sodium 1 part Alumina / magnesium hydroxide 0.5 part

[Prescription]
Sodium polyacrylate (4 parts) and glycerin (13.6 parts) are added to a mixture of aluminum sulfate (1 part) and purified water (18.6 parts) and kneaded until uniform. Next, glycerin (44.3 parts), propylene glycol (15 parts), carboxyvinyl polymer ("Carbopol 934", manufactured by NOVEON) (2 parts) and magnesium magnesium hydroxide ("Sanamin": Kyowa Chemical Industry Co., Ltd.) (0.5 parts) was gradually added, and diclofenac sodium (1 part) was further added and kneaded.
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and stretched by touching the gel with a finger, and had a strong repulsive force.
On the other hand, the obtained sol was applied on a vinyl chloride support with a knife coater with a clearance of 0.5 mm, aged at 20 ° C. for 3 days, and the transdermal absorbability was measured.

Example 4:
[Ingredients and proportions]
Potassium polyacrylate (viscosity: 525 mPa · s) 4 parts Acrylic acid / sodium acrylate (65/35 (molar ratio)) copolymer
0.5 part Tartaric acid 1 part Synthetic hydrotalcite 1 part Potassium aluminum sulfate 1 part Aluminum oxide 18 parts Glycerin 61.5 parts N-vinylacetamide crosslinked product 2 parts Purified water 5 parts Crotamiton 5 parts Indomethacin 1 part

[Prescription]
To a mixed solution of purified water (5 parts) and glycerin (0.5 parts), a mixture of potassium polyacrylate (4 parts) and an acrylic acid / sodium acrylate copolymer (0.5 parts) was added at a stretch and kneaded sufficiently. Then tartaric acid (1 part), synthetic hydrotalcite ("Alkamac", manufactured by Kyowa Chemical Industry Co., Ltd.) (1 part), potassium aluminum sulfate (1 part), aluminum oxide (18 parts), N-vinylacetamide crosslinking (2 parts) and a mixed solution of glycerin (61 parts) were gradually added and kneaded again. After confirming the homogeneity, a solution of crotamiton (5 parts) and indomethacin (1 part) was gradually added and kneaded until uniform.
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and stretched by touching the gel with a finger, and had a strong repulsive force.

Example 5:
[Ingredients and proportions]
Sodium acrylate / potassium methacrylate (50/50 (molar ratio)) copolymer (viscosity: 513 mPa · s) 30 parts Lactic acid 0.01 parts Aluminum hydroxide 0.01 parts Sorbitol polyglycidyl ether 0.1 parts Glycerin 19 .88 parts 1,3-butanediol 10 parts Propylene glycol 10 parts Purified water 30 parts

[Prescription]
A mixture of a sodium acrylate / potassium methacrylate copolymer (30 parts) and glycerin (19.88 parts) was added all at once to purified water (30 parts) and kneaded sufficiently until uniform. Next, lactic acid (0.01 part), sorbitol polyglycidyl ether (“Denacol EX-614B”: manufactured by Nagase Kasei Kogyo Co., Ltd.) (0.1 part), dried aluminum hydroxide gel (Kyowa Chemical Industry Co., Ltd.) (0.01 part) ), 1,3-butanediol (10 parts) and propylene glycol (10 parts).
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and stretched by touching the gel with a finger, and had a strong repulsive force.

Example 6:
[Ingredients and proportions]
Sodium polyacrylate (viscosity: 560 mPa · s) 2 parts Glycerin 75.5 parts Aluminum sulfate 0.5 parts Alumina / magnesium hydroxide 0.15 parts Dry aluminum hydroxide gel 0.20 parts Water 20.025 parts Sodium hydroxide 0. 625 parts Carboxyvinyl polymer 1 part

[Prescription]
To a mixture of water (12.025 parts) and aluminum sulfate (0.5 parts), add a dispersion of sodium polyacrylate ("Biscomate F480SS": Showa Denko KK) (2 parts) and glycerin (10 parts) and mix. did. When the polymer begins to dissolve and thickens, glycerin (65.5 parts) and carboxyvinyl polymer ("AQUPEC HV-504E" manufactured by Sumitomo Seika Co., Ltd.) (1 part), dried aluminum hydroxide gel (Kyowa Chemical Industry Co., Ltd.) ), Low water content type) (0.20 parts) and a mixture of alumina and magnesium hydroxide ("Sanalumin": Kyowa Chemical Industry Co., Ltd.) (0.15 parts), and finally sodium hydroxide (0.625 parts) And a solution of water (8.00 parts) was gradually added and kneaded until uniform.
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and stretched by touching the gel with a finger, and had a strong repulsive force.

Example 7:
[Ingredients and proportions]
Sodium polyacrylate (viscosity: 560 mPa · s) 2 parts Glycerin 68.6 parts Isopropyl myristate 7 parts Aluminum sulfate 0.25 parts Alumina / magnesium hydroxide 0.25 parts Water 20.153 parts Sodium hydroxide 0.547 parts Poly Oxyethylene sorbitan monooleate 0.20 part Carboxyvinyl polymer 1 part

[Prescription]
A mixture of water (12.153 parts), polyoxyethylene sorbitan monooleate ("Tween80", manufactured by Wako Pure Chemical Industries, Ltd.) (0.20 parts) and aluminum sulfate (0.25 parts) was mixed with sodium polyacrylate ("Biscomate F480SS"). : Showa Denko KK (2 parts) and glycerin (10 parts) were added and mixed. When the polymer starts to dissolve and thickens, glycerin (58.6 parts), isopropyl myristate (7 parts), carboxyvinyl polymer ("AQUPEC HV-504E", manufactured by Sumitomo Seika Co., Ltd.) (1 part) and water A mixed solution with alumina / magnesium oxide (“Sanamin”: manufactured by Kyowa Chemical Industry Co., Ltd.) (0.25 parts) was added, and finally a solution of sodium hydroxide (0.547 parts) and water (8.00 parts) was gradually added. Kneaded until uniform.
After the obtained sol was molded and sealed, it was aged at about 50 ° C. for 1 day, then taken out of the container, and the gel was stretched when touched with a finger, and had a strong repulsive force.

Comparative Example 1:
[Ingredients and proportions]
Acrylic acid / sodium acrylate = 30/70 (molar ratio) copolymer (viscosity 531 mPa · s) 4 parts Glycerin 74 parts Aluminum sulfate 1 part Alumina hydroxide / magnesium 1 part Water 16.75 parts Sodium hydroxide 1.25 Part Carboxyvinyl polymer 2 parts

[Prescription]
A mixture of water (10 parts) and aluminum sulfate (1 part) was mixed with acrylic acid / sodium acrylate copolymer (“Biscomate NP-600”, manufactured by Showa Denko KK) (4 parts) and glycerin (10 parts). ) Was added and mixed. When the polymer begins to dissolve and thickens, glycerin (64 parts) and carboxyvinyl polymer ("AQUPEC HV-504E" manufactured by Sumitomo Seika Co., Ltd.) (2 parts) and magnesium alumina hydroxide ("Sanamin"): A mixed solution with Kyowa Chemical Industry Co., Ltd. (1 part) was added, and finally, a solution of sodium hydroxide (1.25 parts) and water (6.75 parts) was gradually added and kneaded until uniform.
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and touched with the gel with a finger. As a result, there was no repulsion, glycerin exuded, and the sol adhered to the finger.

Comparative Example 2:
[Ingredients and proportions]
Polyacrylic acid 4 parts Glycerin 74 parts Aluminum sulfate 1 part Alumina hydroxide / magnesium 1 part Water 16.75 parts Sodium hydroxide 1.25 parts Carboxyvinyl polymer 2 parts

[Prescription]
To a mixture of water (10 parts) and aluminum sulfate (1 part), a dispersion of polyacrylic acid (Mw = 4,000,000: Aldrich) (4 parts) and glycerin (10 parts) was added and mixed. When the polymer begins to dissolve and thickens, glycerin (64 parts) and carboxyvinyl polymer ("AQUPEC HV-504E", manufactured by Sumitomo Seika Co., Ltd.) (2 parts) and magnesium alumina hydroxide ("Sanamin") : A mixture with Kyowa Chemical Industry Co., Ltd. (1 part) was added, and finally a solution of sodium hydroxide (1.25 parts) and water (6.75 parts) was gradually added and kneaded until uniform.
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and touched with the gel, and there was no repulsion at all, and the sol adhered to the finger.

Comparative Example 3:
[Ingredients and proportions]
Sodium polyacrylate (viscosity 560 mPas) 4 parts Glycerin 30 parts Aluminum sulfate 1 part Purified water 61.5 parts Carboxyvinyl polymer 2 parts Diclofenac sodium 1 part 0.5 parts magnesium hydroxide / magnesium 0.5 part

[Prescription]
Sodium polyacrylate (4 parts) and glycerin (13.6 parts) are added to a mixture of aluminum sulfate (1 part) and purified water (61.5 parts) and kneaded until uniform. Next, glycerin (16.4 parts), carboxyvinyl polymer ("Carbopol 934", manufactured by NOVEON) (2 parts) and magnesium alumina hydroxide ("Sanamin": manufactured by Kyowa Chemical Industry Co., Ltd.) (0.5 parts) The mixed solution was gradually added, and diclofenac sodium (1 part) was further added and kneaded.
After the obtained sol was molded and sealed, it was aged at about 20 ° C. for 3 days, then taken out of the container and stretched by touching the gel with a finger, and had a strong repulsive force.
On the other hand, the obtained sol was applied on a polyvinyl chloride support with a knife coater with a clearance of 0.5 mm, aged at 20 ° C. for 3 days, and the transdermal absorbability was measured.

Test Example: Percutaneous Absorption of Diclofenac Sodium Patch 180g to 220g of Wister rat was shaved on the back, and the patches of Example 3 and Comparative Example 3 were applied so that the dose would be 50 mg / kg. The blood concentration over time was measured by HPLC, and the change in plasma concentration was observed. Table 1 shows the results.

The adhesive for a patch of the present invention is obtained by dispersing or dissolving a polymer of a (meth) acrylate and a transdermally absorbable drug in a high-concentration aqueous polyhydric alcohol solution. Of polyhydric alcohols, and they can form a stable substrate without syneresis.
A patch using the pressure-sensitive adhesive for a patch of the present invention is excellent in release characteristics, adhesiveness, and safety.

Claims (13)

When the repeating unit has the general formula (1) or (2)

(In the formula, R ¹ and R ² each independently represent a hydrogen atom or a methyl group, and M represents NH ₄ ⁺ or an alkali metal.)
Wherein (1) / (2) = 100/0 to 90/10 (molar ratio), (meth) acrylic acid-based polymer (A), water (B), polyhydric alcohol (C) and aluminum A pressure-sensitive adhesive composition for a patch, comprising a compound (D) and a water (B) content of 5 to 30% by mass. When the repeating unit has the general formula (1) or (2)

(The meanings of the symbols in the formula are the same as those in Claim 1.)
The pressure-sensitive adhesive composition for a patch according to claim 1, wherein the (meth) acrylic acid-based polymer (A) has a 0.2% by mass aqueous solution viscosity of 400 mPa · s or more.   The pressure-sensitive adhesive composition for a patch according to claim 1, wherein the polyhydric alcohol is a trihydric or higher alcohol.   The pressure-sensitive adhesive composition for a patch according to claim 3, wherein the polyhydric alcohol is glycerin.   The pressure-sensitive adhesive composition for a patch according to claim 1, wherein the content of the polyhydric alcohol is 40 to 94.5% by mass based on the total amount of the composition.   The pressure-sensitive adhesive composition for a patch according to claim 1, wherein a water-soluble aluminum compound and alumina / magnesium hydroxide are used in combination as the aluminum compound.   The pressure-sensitive adhesive composition for a patch according to claim 1, wherein the content of the aluminum compound is 0.01 to 20% by mass relative to the total amount of the composition.   The pressure-sensitive adhesive composition for a patch according to claim 1, further comprising a polymer compound (E) having a high affinity for a polyhydric alcohol.   The pressure-sensitive adhesive composition for a patch according to claim 8, wherein the polymer compound (E) having a high affinity for the polyhydric alcohol is at least one selected from a carboxyvinyl polymer and an N-vinylacetamide-sodium acrylate copolymer. object.   The pressure-sensitive adhesive composition for a patch according to claim 8 or 9, wherein the content of the high molecular compound having a high affinity for the polyhydric alcohol is 0.01 to 20% by mass relative to the total amount of the composition.   The adhesive composition for a patch according to any one of claims 1 to 10, further comprising diclofenac sodium as a medicinal ingredient.   The adhesive composition for a patch according to any one of claims 1 to 10, further comprising capsaicin as a medicinal ingredient. When the repeating unit has the general formula (1) or (2)

(The meanings of the symbols in the formula are the same as those in claim 1.)
Where (1) / (2) = 100/0 to 90/10 (molar ratio), (meth) acrylic acid-based polymer (A), water (B), polyhydric alcohol (C), aluminum A pressure-sensitive adhesive composition for a patch containing the compound (D) as an essential component, optionally containing a polymer compound (E) having a high affinity for a polyhydric alcohol, and having a water (B) content of 5 to 30% by mass. In a method for producing a product, a (meth) acrylic acid-based polymer (A) and a water (B) solution of a polyhydric alcohol (C) are mixed at a water concentration of 50% or more based on their total mass, and then the remaining components are mixed. A patch characterized by adding and mixing (the remaining polyhydric alcohol (C), aluminum compound (D) and, if desired, polymer compound (E)) and adjusting the water concentration to 5 to 30%. Method for producing pressure-sensitive adhesive composition for use.