WO2006090824A1

WO2006090824A1 - Gel composition and method for producing same

Info

Publication number: WO2006090824A1
Application number: PCT/JP2006/303391
Authority: WO
Inventors: Tomoya Nihei; Runa Unagami; Kazuhiko Matsuda; Yoshifumi Yamagata; Hajime Gotoh; Takeyuki Asanuma; Narumi Tagaki; Yasunori Sakamoto
Original assignee: Lion Corporation
Priority date: 2005-02-24
Filing date: 2006-02-24
Publication date: 2006-08-31
Also published as: JP4786196B2; JP2006232724A

Abstract

Disclosed is a gel composition containing a polymer (A) having a repeating unit composed of at least one unsaturated portion and an acid anhydride portion and another repeating unit composed of at least one unsaturated portion and an acid compound portion corresponding to the acid anhydride portion, and a polyhydric alcohol (B). The polymer (A) contains the acid anhydride portion and the acid compound portion corresponding to the acid anhydride portion in a molar ratio of 15/85-85/15. This gel composition exhibits high adhesion to the skin or mucosa, and has excellent gel-forming ability.

Description

Specification

Gel composition and method for producing the same

Technical field

[0001] The present invention relates to a gel composition that can be used as a base for medical patches, wound dressings, taping agents, etc., a patch obtained by spreading the gel composition on a support, and the gel composition It relates to manufacturing methods. More specifically, the present invention relates to a gel composition having high adhesiveness to the skin or mucous membrane and having an excellent gel forming ability.

Background art

[0002] Compared with injection and oral administration, the method of administering a drug by the transdermal and transmucosal absorption route is that the effective concentration of the active ingredient in the body fluid is maintained and can be expected to be sustained immediately, and the absorption of the active ingredient Increased interest in recent years due to easy adjustment of speed, low risk of side effects, and effective use of medicinal ingredients that are less affected by stomach acid, digestive enzymes, etc., and less affected by metabolism due to the first-pass effect of the liver. ing.

[0003] Conventionally, as a base used for administration by the transdermal / transmucosal absorption route, a poultice prepared by adding a water-soluble polymer such as sodium polyacrylate or carboxybule polymer to water, SIS, Tapes with a plasticizer and tackifier added to rubber, silicon and acrylic polymers such as polyisobutylene, plaster agents, oily bases such as liquid paraffin and petrolatum, water absorption such as gelatin and sodium carboxymethylcellulose Ointment bases containing functional polymers are known. However, there is a problem with the nove agent because water evaporates during use, the plaster hardens and the adhesiveness decreases. Although there is little change over time with plaster agents, skin irritation, such as peeling of the stratum corneum due to too strong adhesion, and skin breathing being hindered due to poor moisture permeability, causing rashes and rashes, especially during repeated application. There is a problem of high nature. In addition, since the ointment base has poor adhesion, there is a problem that it does not have sufficient local retention.

[0004] To solve this problem, a hydrophilic polymer such as polyacrylic acid and carboxymethyl cellulose and water, one selected from the group consisting of rosin ester, hydrogenated petroleum resin, and terpene-based resin Medical patch containing the above tackified rosin (see Patent Document 1) ), A pressure-sensitive adhesive composition containing a polymer soluble in a lower alcohol and having a carboxyl group or a salt thereof, a lower alcohol, a polyhydric alcohol, and metal sulphate, and gelled (see Patent Document 2), Adhesive gel base using methyl vinyl ether maleic anhydride copolymer or methyl vinyl ether maleic acid copolymer as the base polymer, polyfunctional epoxy compound as the cross-linking agent, and gelling water and polyhydric alcohol (Patent Literature) 3) has been proposed. However, since these bases contain water or lower alcohol having a relatively low boiling point as the main component, water or lower alcohol evaporates during use, resulting in performance such as stickiness and skin irritation. Has a problem that it deteriorates over time.

[0005] In addition, an anhydrous gel matrix having a hydroxyl group and a Z or carboxyl group in the molecule using a cross-linking agent and gelling the polyhydric alcohol with a polyhydric alcohol-soluble polymer (see Patent Document 4) In addition, a non-aqueous patch (see Patent Document 5) in which a polyhydric alcohol is gelled with a polyhydric alcohol-soluble polymer and a strong ropoxyvinyl polymer has also been proposed. Since these bases are mainly polyhydric alcohols, there is almost no deterioration in performance over time, but in order to improve gel forming ability, in addition to polyhydric alcohols and polyhydric alcohol soluble polymers, In addition, it is essential to add a cross-linking agent and a superabsorbent polymer compound, and the manufacturing operation may be complicated.

[0006] A non-aqueous thermal gel composition (see Patent Document 6) characterized by containing a polyhydric alcohol and a power that dissolves in the polyhydric alcohol or a polymer that swells with the polyhydric alcohol has also been proposed. ing. Since the main component of this base is a polyhydric alcohol, the essential components that hardly deteriorate with time are a polyhydric alcohol and a polymer, and it is expected that the manufacturing operation is simple. However, there are cases where the adhesiveness and gel-forming ability are insufficient, with no mention of adhesiveness and gel-forming ability.

[0007] Patent Document 1: Japanese Patent Laid-Open No. 6-254150

Patent Document 2: Japanese Patent Laid-Open No. 9-143062

Patent Document 3: Japanese Patent Laid-Open No. 9-286891

Patent Document 4: Japanese Patent Laid-Open No. 63-203162

Patent Document 5: Japanese Patent Laid-Open No. 2003-113077

Patent Document 6: Japanese Patent Laid-Open No. 2001-245913 Disclosure of the invention

Problems to be solved by the invention

[0008] Accordingly, the present invention provides a gel composition having high adhesion to skin or mucous membrane and having an excellent gel-forming ability, a patch using the gel composition, and a method for producing the gel composition. The purpose is to do.

Means for solving the problem

[0009] As a result of intensive studies to achieve the above object, the present inventors have found that a polymer and a polyhydric alcohol in which the acid anhydride portion and the corresponding acid compound portion in the polymer are in a specific range. Thus, the inventors have found that a gel composition having high adhesion to the skin or mucous membrane and having an excellent gel forming ability can be obtained, and the present invention has been completed.

That is, the present invention comprises (A) a repeating unit composed of at least one unsaturated portion and an acid anhydride portion, and at least one unsaturated portion and an acid compound portion corresponding to the acid anhydride portion. A gel composition comprising a polymer containing a repeating unit, and (B) a polyhydric alcohol,

(A) The gel composition is characterized in that the polymer contains an acid anhydride portion and an acid compound portion corresponding to the acid anhydride portion in a molar ratio of 15Z85 to 85Z15.

The present invention also provides a patch in which the gel composition is spread on a support.

[0010] The present invention also includes (a) hydrolyzing a polymer containing a repeating unit composed of at least one unsaturated portion and an acid anhydride portion, and an acid anhydride portion contained in the polymer. (A) a repeating unit composed of at least one unsaturated portion and an acid anhydride portion, wherein the acid compound portion corresponding to the acid anhydride portion is a molar ratio of 15Z85 to 85Z15, Obtaining a polymer comprising a repeating unit composed of at least one unsaturated moiety and an acid / acid compound moiety corresponding to the acid anhydride moiety,

A step of dissolving the obtained (A) polymer in (B) a polyhydric alcohol; and

Heating the resulting mixture in the absence of a crosslinking agent;

A method for producing a gel composition is provided. The invention's effect

[0011] According to the present invention, it is possible to provide a gel composition having high adhesion to the skin or mucous membrane and having an excellent gel forming ability. According to the present invention, it is also possible to provide a gel composition that hardly causes skin irritation with a small deterioration power S of performance.

[0012] According to the gel composition of the present invention, it is possible to provide an external preparation composition such as a patch excellent in transdermal absorbability of a medicinal component, preferably excellent in initial transdermal absorbability.

In addition, the gel composition of the present invention is excellent in solubility of medicinal components, particularly medicinal components that are difficult to absorb percutaneously, and can provide an external preparation composition with an increased amount of medicinal components.

The gel composition of the present invention also has good usability and can be applied to various preparations.

BEST MODE FOR CARRYING OUT THE INVENTION

[0013] (A) Consists of a repeating unit composed of at least one unsaturated moiety and an acid anhydride moiety, and at least one unsaturated moiety and an acid compound moiety corresponding to the acid anhydride moiety. Containing repeating units

The polymer (A) used in the present invention has a mono ktt force of 15/85 to 85/15, preferably 15/85 of an acid anhydride portion and an acid compound portion corresponding to the acid anhydride portion. -80/20, more preferably 20Z80-70Z30. Within such a range, it is preferable because it has both high adhesiveness and excellent gel forming ability. If the ratio of the acid anhydride is too high, it becomes difficult to obtain a gel composition having both high tackiness and excellent gel-forming ability. If the ratio of the acid compound portion is too high, the gel composition has excellent gel-forming ability. It becomes difficult to obtain a gel composition. In the present invention, the molar ratio between the acid anhydride and the acid compound portion corresponding to the acid anhydride portion can be measured by potentiometric titration. (Ii) The polymer has the same number of moles of at least one unsaturated portion as the sum of the number of moles of the acid anhydride portion and the number of moles of the acid compound portion corresponding to the acid anhydride portion. I like it.

[0014] The weight average molecular weight of the (ii) polymer of the present invention is preferably high enough to obtain good gel-forming ability, for example, 10,000 to 10,000,000, preferably 100,000 to 5,000,000. This average molecular weight is a value measured by a size exclusion separation low angle laser light scattering detector method. The blending amount of the polymer with respect to the gel composition of the present invention is, for example, 1 to 55 quality. The amount is preferably 1 to 40% by mass, more preferably 1 to 30% by mass.

[0015] In the polymer (A) of the present invention, it is preferable that at least one unsaturated portion is a beluie compound. Examples of the vinyl compound include methyl vinyl ether, styrene, ethylene, isobutylene and the like. Of these, methyl beryl ether is preferred.

The acid anhydride portion is preferably selected from the group strength of maleic anhydride portion and itaconic anhydride partial force. More preferably, (A) the polymer is an alkyl butyl ether having 3 to 24 carbon atoms, a maleic anhydride, a maleic anhydride, a maleic acid copolymer, an alkyl bulle ether having 3 to 24 carbon atoms, and itaconic anhydride. Z-taconic acid power Constructed copolymer power is selected. More preferred are a copolymer composed of methyl vinyl ether Z maleic anhydride Z maleic acid and a copolymer composed of methyl vinyl ether Z itaconic anhydride Z itaconic acid. Of these, a copolymer composed of methyl vinyl ether Z maleic anhydride and maleic acid is most preferred.

[0016] The (A) polymer of the present invention includes, for example, a monomer containing at least one unsaturated moiety, a monomer containing an acid anhydride moiety, and a monomer containing an acid compound moiety corresponding to the acid anhydride moiety. It can also be produced by copolymerization or (a) by hydrolysis of a polymer containing a repeating unit composed of at least one unsaturated moiety and an acid anhydride moiety. As such (a) polymer, for example, those commercially available from ISP as GA NTREZ AN series can be used.

Hydrolysis is performed, for example, on (a) 100 parts by mass of polymer, 2 to: LOO parts by mass, preferably 2 to 50 parts by mass of water, and at a temperature of 20 to 100 ° C. for 1 to 600 minutes, This can be done by reacting. As for the method of adding water, the polymer may be dissolved in a solvent such as acetone, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide in advance, and water may be added thereto, or water may be sprayed onto the polymer. The polymer may be absorbed as water vapor. By using an amount of water in this range, even when the gel composition of the present invention is formulated into a patch or the like, it is possible to reduce the degree to which the adhesiveness or the like decreases with time during use. The obtained polymer can be used as it is, or it can be used after removing water present in the system to about 1% with respect to the polymer by heating, drying under reduced pressure or the like. [0017] Specifically, the polyhydric alcohol used in the present invention preferably does not evaporate during use. For example, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, trimethylolpropane, di-ethylene. Glycerin, triglycerin, polyglycerin, polyethylene glycol, dipropylene glycol, triethylene glycol, polyethylene glycol monourea (weight average molecular weight 200-2000, preferably 200-600), positive P-pilling !; = 3— (weight Average molecular weight 400-4000, preferably 400-1000), polyethylene 'polypropylene monole (weight average molecular weight 1000-6000, preferably <1000-3000), positive aged hydrogenated castor oil (5E.O.-100E) O., preferably 10E. O. to 60E. O.) and sorbitol, etc., and these may be used alone or in combination of two or more. Can be used in appropriate combinations.

[0018] Among them, the weight average molecular weight is 200 to 2000, more preferably 200 to 1500, more preferably <is 200 to 1000, and particularly preferably <is 200 to 600. . When polyethylene glycol is used, it is particularly preferable to use a polyvalent alcohol other than polyethylene glycol because the transdermal absorbability of the medicinal component is improved. Examples of polyhydric alcohols other than polyethylene glycol include dihydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol and dipropylene glycol, and trivalent alcohols such as glycerin and trimethylolpropane. Particularly preferred are dihydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol and dipropylene glycol. When used in combination, it is preferably used as a dihydric or hexahydric polyhydric alcohol mixture containing polyethylene glycol having a weight average molecular weight of 200 to 2000! /.

The mixing ratio of polyethylene glycol and divalent to 6-valent polyhydric alcohols other than polyethylene glycol is 1: 9-: LO: 0 is preferred by mass ratio 1: 9-9: 1 is more preferred 2 : 8-8: 2 is more preferable. Within such a range, the percutaneous absorbability of the medicinal component having high solubility of the medicinal component is further increased, which is preferable.

In addition, the measuring method of the weight average molecular weight of the polyhydric alcohol which is a polymer can be measured by a titration test described in the cosmetic raw material standards.

[0019] The blending amount of the polyhydric alcohol with respect to the gel composition of the present invention is, for example, 40 It is 50 mass%-99 mass%, Preferably, it is 50 mass%-99 mass%, More preferably, it is 60 mass%-99 mass%. Further, the total amount of the polymer (A) and the polyvalent alcohol in the gel composition of the present invention is, for example, 60% by mass or more, preferably 65% by mass or more, and more preferably 70% by mass or more. Hope U ,.

The mass ratio of the polymer (A) of the present invention to the polyhydric alcohol is 1Z99 to 55Z45, preferably 1Z99 to 45Z55, and more preferably 1Z99 to 35Z65.

[0020] The gel composition of the present invention may optionally contain a polymer that dissolves or swells in the polyhydric alcohol used. Here, dissolution means that a polyvalent alcohol solution of 1% by mass of a polymer becomes uniform. Swelling refers to a state in which a polymer absorbs polyhydric alcohol and increases its volume when mixed with a certain mass of polyhydric alcohol, and the mass of this polyhydric alcohol mixture is the polymer before mixing. This is when the mass is twice or more. The polymer is preferably gelled by dissolving or swelling in a polyhydric alcohol. Specifically, for example, hydroxypropyl cellulose, hydroxyethyl cellulose, polypyrrolidone, carboxyvinyl polymer, (meth) acrylic acid Z (meth) acrylic acid ester copolymer, N-methacryloyl ethyl N, N Dimethylammomu α- Ν— Methyl carboxybetaine polymer, polyacrylic acid, polyacetic acid butyl, polybutyl alcohol, poly ビュ bulucacetamide, polymethoxypolyethylene glycol (meth) acrylate, polyphenoxypolyethylene Glycol (meth) acrylate, polyhydroxyethyl (meth) acrylate, polyhydroxypropyl (meth) acrylate, polyacrylamide, acrylic acid Ζ acrylamide ェ ethyl acrylate copolymer, methacrylic acid copolymer, and isobutyl It can be exemplified emissions, and these may be used singly or in combination of two or more appropriately.

[0021] The gel composition of the present invention may optionally contain additives such as pressure-sensitive adhesives, binders, medicinal ingredients, transdermal absorption enhancers, other active ingredients, perfumes, and pigments. It is preferable to contain at least one selected from the group consisting of a pressure-sensitive adhesive, a binder, and a mixture thereof because the pressure-sensitive adhesiveness of the gel composition of the present invention can be improved. Further, when the gel composition of the present invention contains a medicinal component, it is preferable because the medicinal effect can be sustained. When the transdermal absorption enhancer is contained, the gel composition of the present invention contains a medicinal component. It is preferable because the percutaneous absorbability of the medicinal component, particularly the initial percutaneous absorbability, is improved. The additive used in the present invention is not particularly limited as long as it can be dissolved or dispersed in a polyhydric alcohol. Examples of active ingredients include warm sensation active ingredient, cool sensation active ingredient, terminal circulation promoting agent, anti-inflammatory analgesic ingredient, blood circulation promoter, local anesthetic agent, antiperspirant, athlete's foot drug, antibacterial / bactericidal ingredient, Antibacterial and sterilizing agents, whitening ingredients, sebum suppressants, keratolytic agents, active ingredients for cervical sprains, and astringent ingredients. These can be used alone or in combination of two or more.

[0022] Ku adhesives>

Adhesives such as rosin ester, alicyclic resin, and polyterpene resin are mixed with elastomers such as styrene Z isoprene Z styrene block copolymer (SIS) and polyisobutylene (PIB). Rubber adhesives; acrylic adhesives such as polyacrylic acid, polyacrylate (preferably sodium salt), acrylic acid Z methacrylic acid copolymer; silicone adhesives such as polysiloxane derivatives; alkyl Examples include vinyl ether-based adhesives such as vinyl ether Z maleic anhydride copolymer; and butyl acetate-based adhesives such as acrylic ester Z vinyl acetate copolymer. These pressure-sensitive adhesives may be used alone or in combination of two or more. Acrylic adhesives and vinyl ether adhesives are more preferably used.

[0023] The mass average molecular weight of the pressure-sensitive adhesive is preferably 10,000 to 10,000,000, more preferably 10,000 to 50,000,000!

The blending amount of the pressure-sensitive adhesive is preferably 1 to 78% by mass, more preferably 5 to 75% by mass in the composition. If it is at least the lower limit of the range, sufficient adhesion to the use site of the gel composition is obtained, and if it is at most the upper limit, the peelability of the use site force of the gel composition is good.

[0024] <Binder>

Examples of the binder include carboxyvinyl polymer, alginic acid, polybutyl alcohol, polyvinyl pyrrolidone, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and the like. Among these, carboxyvinyl polymer and hydroxypropylcellulose are preferred, and hydroxypropylcellulose is more preferred. The weight average molecular weight of the binder is preferably 10,000 to 100,000,000, more preferably 50,000 to 5,000,000. The weight average molecular weight of the binder is

It can be measured by gel permeation chromatography method or light scattering method. In particular, in the case of a carboxy polymer, a value converted into polyethylene oxide by gel permeation chromatography method, and in the case of hydroxypropyl cellulose, gel permeation. Use the value calculated by pullulan conversion by the Chillon chromatography method, or the value measured by the light scattering method in the case of polybulurpyrrolidone.

These binders may be used alone or in combination of two or more.

The blending amount of the binder is preferably 1 to 30% by mass and more preferably 1 to 20% by mass in the composition. If it is this range, the retention property of the composition in the applied part will become favorable, and the sustainability of a medicinal effect can be improved.

When a mixture of an adhesive and a binder is used, the blending amount of the mixture is preferably 1 to 78% by mass, more preferably 5 to 75% by mass in the composition.

The medicinal properties include non-steroidal anti-inflammatory drugs such as indomethacin, fuel binac, ketoprofen, flurbiprofen, diclofenac, and ester derivatives thereof; antihistamines such as diphenhydramine, central nervous system drugs such as isoprenaline hydrochloride, estradiol and testosterone Hormonal agents; analgesics such as aspirin, acetaminophen, ibuprofen; antiarrhythmic agents such as disopyramide phosphate; coronary vasodilators such as tolazoline hydrochloride; local anesthetics such as lidocaine; muscle relaxants such as skisamethonium chloride; Antifungal agents such as clotrimazole, anti-neoplastic agents such as fluorouracil, dysuria such as tamsulosin hydrochloride, antiepileptic agents such as diazepam, antiparkinsonian agents such as bromocriptine mesylate, antihypertensive agents such as furosemide and clodine Vasodilators such as nitroglycerin and isosorbide nitrate, smoking cessation aids such as nicotine, bronchodilators such as lobbutale, hypnotic sedatives such as phenovalpital and triazolam, tranquilizers such as fluphenazine and theoritadine; vitamin A, vitamin Vitamins such as E, vitamin K, octothiacin, riboflavin butyrate; prostaglandins, scopolamine, fentanyl, etc.

[0026] The active ingredients for warm feeling include, for example, red pepper extract, red pepper tincture, kabusaicin, Twilight extract, meat katsura, ginger extract, ginger alcohol extract, cantalis tincture

, Nicotinic acid benzyl ester, vitamin E, borneol, dl-camphor, 1-menthol, heart force oil, eucalyptus oil, methyl salicylate, glycol salicylate, リル -allyl alcohol derivatives, ヮ -rilamide of norlate, vanillyl Examples include alcohol alkyl ethers, pepper family plant extracts, sage genus plant extracts, argentia genus plant extracts, clove oil, and eugenol derivatives. When these components are added, blood circulation can be promoted using a local or induced stimulus to the skin, and a warm feeling can be obtained. Active ingredients for cooling sensation include, for example, menthol, menthol glycerol ether, and derivatives of these compounds such as esters, N-ethyl-p-3-menthane-carboxamide, heart force oil, and force flu. When these components are added, a cool sensation can be obtained by utilizing local or induced irritation to the skin.

[0027] The peripheral circulation promoting agent includes, for example, tocolol acetate. Anti-inflammatory analgesic components include, for example, salicylic acid, methyl salicylate, glycol salicylate, diphenhydramine, chlorfelamamine maleate, ammonium glycyrrhizinate, dicalium glycyrrhizinate, glycyrrhizic acid, stearyl glycyrrhizinate, 13-darlicylretinoic acid, , Azulene, _ε -aminocaproic acid, hydrocortisone, calcium pantothenate, ethyl pantothenate, hydrocortisone acetate, nor-hydroxamide, diphenol hydramine, indomethacin, ketoprofen, flurbiprofen, ibuprofen, suprofen, Loxoprofen, Zaltoprofen, Piroxicam, Fuerbinac, Arnica tincture, Licorice, Yellow ream, Sikon, Western sawtooth grass, Spiral grass, Aloe, Vitamin There is an ester, and the like. Examples of active ingredients for cervical spine include aminoalkoxybibenzyls.

[0028] Examples of the blood circulation promoter include senpri extract, cephalanthin, vitamin Ε and its derivatives, Ί oryzanol, peppermint oil, turpentine oil, thiodi oil, geraol oil, thymol oil, wikiyou oil, bergamot oil, anise Oil, Lavender oil, Black pepper oil, Beninona oil, Anole extract, Maronier extract, Enmeiso extract, Bodaige extract, Melissa extract, ェ ethyl ρ-3-menthane monocarboxamide, etc. Examples of local anesthetics include funnel extract, jib force-in, pro force-in, and lidocaine. Yield Tannin-containing components are preferably used as the brick component. There are abalone grass, white birch, Daio etc. An inorganic salt is preferably used as the perspiration promoter. For example, calcined gypsum, calcium chloride, anhydrous calcium chloride, magnesium chloride, anhydrous magnesium chloride, calcium carbonate, anhydrous calcium carbonate, sodium sulfate, anhydrous sodium sulfate, magnesium sulfate, anhydrous magnesium sulfate, sodium hydroxide, potassium hydroxide Sodium chloride, potassium chloride, zeolite, montmorillonite, smectite, kaolin, talc, clay minerals, and various other salts.

[0029] Sterilization · Antibacterial components include, for example, pyrotatone olamine, cyclopilotas olamine, benzalkonium chloride, benzethonium chloride, halocarban, clohexhexidine hydrochloride, zinc pyrithione, phenol, trichlorocarba -Lido, chlorhexidine dalconate, cetyl pyridinium chloride, isopropylmethylphenol, allantoin, anti-plasmin agent (ε-aminocaproic acid, tranexamic acid), dihydrocholesterol, tonic extract, force mitre (containing azulene), There are essential oils such as eucalyptus oil and hinokitiol. As the athlete's foot drug, for example, quinuhada (Callophyllis flabellulata) water extract, which is an active ingredient, miconazole nitrate, and other antipruritic agents, diphenhydramine hydrochloride, chlorfelamine maleate, camphor, and labrite are used.

[0030] Antibacterial 'bactericidal agents include, for example, zinc pyrithione, trichlorocarbalide, triclosan, aloe extract, carrot extract, licorice extract, wolverine extract, force extract, birch extract, water-soluble cerium salt, abietic acid, pimaric acid, Sulfur containing bis (2-pyridinethiol 1 oxide) zinc, pyridinethione salt, histamine 2 receptor antagonist, vitamin E acetate, pantothruethyl ether, citrate triethyl ester, methionine, cystine, cysteine, etc. Amino acids and their hydrochlorides, extracts from cinnamon 'clove' time 'penzoin' oak moss' vanilla, zinc pyrithione, 10-aryl 1,8-dihydroxyanthrone, sodium benzoate, anthocyanins, anthocyanins, pipettes Razine derivative, uric acid, Tyne acids, rutin, 1-hydroxy - 2-pyridones, sulfite ion generating water-soluble salts, sodium Aruminokei acid, oil-soluble licorice extract, and Rapora There is it. Such antibacterial 'disinfectants can generally be used as antidandruff agents.

[0031] A whitening component, a sebum inhibitor, a keratolytic agent, and the like can be used mainly when used as a cosmetic. Whitening ingredients include, for example, arbutin, ellagic acid, kojic acid, hydroquinone, vitamin C, placenta extract, titanium oxide, water extract of Callophyllis japonica, and water extract of Callophyllis adhaerens. There is. Examples of sebum inhibitors and keratolytic agents include estradiol, estrone, ethynylestradiol, vitamin B6, io, resorcin, benzalkonium chloride, benzethonium chloride, halocarban, 2, 4, 4 —Trichrome mouthpieces 2-hydroxyphenol, selenium sulfide, pentadecanoic acid, pentadecanoic acid derivatives, various vitamins, etc.

[0032] Among them, non-steroid anti-inflammatory agents such as indomethacin, fuerbinac, ketoprofen, flurbiprofen, diclofenac and the like, which are preferably poorly water-soluble medicinal ingredients because the effects of the present invention are particularly remarkable; estradiol, testosterone, etc. Hormonal agents, antihypertensive agents such as furosemide and clonidine, vasodilators such as nitroglycerin and isosorbide nitrate, smoking cessation aids such as nicotine, bronchodilators such as lolobtail, scopolamine and fentanyl are more preferred. More preferred are indomethacin, fuel binac, ketoprofen and flurbiprofen. These medicinal ingredients may be used alone or in combination of two or more.

In addition, “poorly water-soluble medicinal ingredient” is an index of sparingly soluble, for example, when it shows solubility in water according to the Japanese pharmacy property test, “very insoluble!” Or “almost insoluble! /, "The medicinal ingredient for which the term" is used.

The compounding amount of the medicinal component in the gel composition of the present invention can be appropriately set by those skilled in the art, and is preferably about 0.05 to 70% by mass in the composition.

[0033] <Transdermal absorption enhancer>

As a transdermal absorption enhancer, the following formula (1):

(R ² OOC)-R ¹ -R ³ (1)

[Wherein R ¹ is a hydrocarbon group having 3 to 36 carbon atoms, R ² is a hydrocarbon group having 1 to 20 carbon atoms, R ³ is a hydrogen atom or —COOR ⁴ and R ⁴ is 1 carbon atom. ~: It is a hydrocarbon group of L0. ] The ester represented by these is mention | raise | lifted. R ¹ represents a hydrocarbon group having 3 to 36 carbon atoms, preferably 4 to 20 carbon atoms, which may be linear, branched or saturated or unsaturated. Good. A carbon number in this range is preferable because it is excellent in transdermal absorbability of medicinal ingredients and solubility in polyhydric alcohols including polyethylene glycol. When R ³ is a hydrogen atom, the number of carbon atoms is preferably 10 to 36. When COOR ⁴ is selected, the number of carbon atoms is preferably 3 to 20.

R ² represents a hydrocarbon group having 1 to 20 carbon atoms, preferably 1 to 18 carbon atoms, which may be linear, branched or saturated or unsaturated. Good. In addition, when R ³ is a hydrogen atom, the number of carbon atoms is preferably 1-18. When R ³ is one COOR ^4, the number of carbon atoms is preferably from it preferably instrument is 1-10 1-6, more preferably 1-3.

R ³ represents a hydrogen atom or COOR ⁴ and R ⁴ represents a hydrocarbon group having 1 to 10 carbon atoms, preferably 1 to 8 carbon atoms, and the hydrocarbon group may be linear or branched. It may be saturated or unsaturated. R ² and R ⁴ may be the same as or different from each other.

[0034] Specific examples of the transdermal absorption enhancer include decyl sebacate, diisopropyl sebacate, decyl adipate, diisopropyl adipate, oleyl oleate, isopropyl myristate, isopropyl palmitate, ethyl linoleate, isopropyl linoleate. And the like. Of these, decyl sebacate, diisopropyl sebacate, diisopropyl adipate, oleyl oleate, and isopropyl myristate are preferred. Especially preferred is Jetyl Sebacate! /.

These transdermal absorption enhancers may be used alone or in combination of two or more. The blending amount of the transdermal absorption enhancer is preferably 1 to 50% by weight in the composition, 3 to 40% by weight, more preferably 5 to 30% by weight, and even more preferably 10 to 30% by weight. preferable. Within such a range, the transdermal absorbability of the medicinal component is good.

[0035] The mixing ratio of the polyhydric alcohol and the transdermal absorption enhancer is preferably 1: 9 to 9: 1 in terms of mass ratio, more preferably 2: 8 to 8: 2. Within this range, both the solubility of the medicinal component and the transdermal absorbability of the medicinal component are excellent.

Examples of the transdermal absorption enhancer include crotamiton and benzyl alcohol, and these can be used singly or in appropriate combination of two or more. [0036] Examples of the fragrances include amylcinnamic aldehyde, benzyl acetate, p-tert butynolecyclohexenole acetate, cyclaset, cyclaprop, garaki solid, bedeon, orange oil and the like. The dye is not particularly limited, and the dyes described in the Legal Dye Handbook can be blended. For example, Red 2, Green 3, Blue 1, Dai 402, Yellow 401, Purple 401, etc. is there.

[0037] The gel composition of the present invention can be produced by dissolving (A) a polymer in (B) a polyhydric alcohol, and performing a crosslinking reaction with the polyhydric alcohol to form a gel. In the present invention, when (A) the polymer is dissolved in (B) polyhydric alcohol and subjected to a crosslinking reaction, it is preferable to perform a heat treatment in order to promote the dissolution / crosslinking reaction. The heating may be performed while kneading or kneading (A) the polymer and (B) the polyhydric alcohol. In addition, the slurry containing (A) the polymer and (B) the polyhydric alcohol is made into a nonwoven fabric or the like. This may be done after application to the support. The heating temperature is different depending on the (B) polyhydric alcohol used. (B) In the range not exceeding the boiling point of the polyhydric alcohol, for example, about 20 ° C to 250 ° C, preferably 40 ° C to It is desirable that the temperature be about 200 ° C, more preferably about 60 ° C to 180 ° C. The heating time is, for example, 10 minutes to 10 hours, preferably 30 minutes to 4 hours.

[0038] The gel composition of the present invention is not particularly limited in its use and dosage form. For example, it is used as an external preparation composition that can be applied to skin, hair, oral cavity (including mucous membranes), nails and the like. Is possible. The dosage form is not particularly limited, and includes patches (medical patches, wound dressings, tabing agents, foot care sheet agents, knock agents, mask agents), ointments, gels, and coating agents. In particular, a patch is preferred. The coating amount of the external preparation composition is preferably about 0.01 to about Lg / cm ² , for example, depending on the types of medicinal ingredients and binders used. The composition for external use can be produced by a conventional method.

In the present invention, the patch is obtained by spreading the gel composition on a support, and the spreading method is not particularly limited, and can be performed using a known apparatus, for example, a roll coater. A knife coater, a slit die coater, a gravure coater or the like can be used. Moreover, as a support body, a well-known thing can be used, For example, paper, a knitted fabric, a woven fabric, a nonwoven fabric, a polymer film, or those laminated bodies etc. can be mentioned. Materials for knitted fabric, woven fabric, non-woven fabric, and polymer film include polyester, polypropylene, rayon, Examples include butyl chloride, polyethylene, polyurethane, and polyurethane 'vinyl chloride copolymer film. The amount of spreading when the gel composition is spread on the support is not particularly limited, and it is 0.001 to 1 lg / cm ² , preferably 0. 003 to 0.5 g / cm ² , more preferably 0.005 to 0.2 gZcm ² .

[0039] It should be noted that the patch of the present invention, after spreading the gel composition, is used as needed for the purpose of preventing volatilization of medicinal ingredients, protecting the adhesive surface, etc. A facing layer may be provided on the top and covered. The facing layer is not particularly limited as long as it can protect the patch, and examples thereof include plastic films such as polypropylene film, polychlorinated bull film, polyethylene film, and polyethylene terephthalate film, and release paper. The patch can then be cut into an appropriate size and used. The cutting method may be any cutting method such as slitting, cutting by push-cutting, or a combination of these, or the punching cutting method.

According to the ball tack value CFIS Z-0237 test, the adhesive patch of the present invention has an adhesive strength adjusted to 4 to 32, preferably 6 to 30, when measured at an inclination angle of 30 °. Is preferred. If it is at least the lower limit of the range, sufficient adhesion to the site of use of the patch can be obtained, and if it is not more than the upper limit, the patch can be peeled off with little skin irritation.

The adhesive strength of the patch can be adjusted by selecting the adhesive and controlling the blending amount.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples.

Example

(Examples 1A to 16A, Comparative Examples 1A to 4A)

Examples 1A to: L 1A, 13A and 14A and Comparative Examples 1A to 4A are gel compositions obtained by kneading each component with a bench-kinder (PNV-1, manufactured by Hitachi, Ltd.) polyester - Tsu DOO such that 0. lgZcm ² on (Toho Textile Co., Ltd.), and uniformly spread by a roll coater (manufactured by Hanae machinery industry Co.), and the sheet.

Example 12A is a polyester knit (manufactured by Toho Textile Co., Ltd.), in which each component was kneaded for 5 minutes at room temperature with a bench-top (PNV-1, manufactured by Hitachi, Ltd.). ) Up 0 It was prepared by heating after uniformly coating with a roll coater (manufactured by Kaei Machine Industry Co., Ltd.) so that lgZcm ² was obtained. The gel forming ability of each gel composition and the adhesiveness of each patch were evaluated by the following methods.

[0041] (Gel forming ability evaluation method)

It is known that the gel composition has a higher gel-forming ability as the storage elastic modulus has a lower frequency dependency. Therefore, the present inventors investigated how much the storage elastic modulus of the prepared gel composition is affected by the change of the measurement frequency, and evaluated the gel forming ability. The storage elastic modulus was measured with a stress-controlled rheometer (Rheo—Stress RS—100, manufactured by Haake) at 25 ° C, and the storage elastic modulus (G ′ (0. 1)) with a frequency of 0. IradZsec. The gel-forming ability was evaluated from the value of the ratio (G, (10) ZG ′ (0.1)) to the storage elastic modulus (G, (10)) of lOradZ sec. Evaluation is G '(10) ZG' (0.1) is 0.67 or more and less than 1.5 `` ◎ '', 0.5 or more and less than 0.67, and 1.5 or more and less than 2 is `` ◯ '', Less than 0.5 and 2 or more were designated as “X”.

[0042] (Adhesion evaluation method)

The produced sheet was evaluated with a texture analyzer (TA-XT2, manufactured by Stable Micro Systems). A probe with a diameter of 20 mm covered with a collagen film was adhered to the sheet with a load of 100 g for 10 seconds, and then the peeling operation when peeling at a peeling speed of lOmmZsec was evaluated as tackiness. The evaluation was “O” for lOOOg'mm or more, “◯” for 500g′mm or more and less than 1000 8'111111, and “” for 50 (^ '111111 or less.

[0043] (Example 1A)

Methyl beryl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN—139) 100 mass%, 8 mass% water added, 90 ° C [Koo! By hydrolyzing, a copolymer (molecular weight: 1.08 million) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a molar ratio of maleic anhydride Z maleic acid of 56Z44 was obtained as polymer (A). .

25 parts by mass of the obtained (A) polymer and 75 parts by mass of polyethylene glycol (PEG400, manufactured by Lion Corporation) were kneaded at 90 ° C. for 90 minutes, and then spread into a sheet.

[0044] (Example 2A)

Methyl beryl ether Z Maleic anhydride Power copolymer (ISP, GAN TREZ AN—139) 100 mass% of water, 15 mass% of water added, and then hydrolyzed at 90 ° C for 300 minutes. (A) As a polymer, maleic anhydride Z maleic acid Thus, a copolymer (molecular weight: 1.08 million) composed of methyl beryl ether Z maleic anhydride Z maleic acid having a molar ratio of 27Z73 was obtained.

[0045] (Example 3A)

Methyl beryl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN—169) Add 100 parts by mass of 4 parts by mass of water and hydrolyze at 90 ° C for 180 minutes As a result, a copolymer (molecular weight: 1.98 million) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a maleic anhydride Z maleic acid molar ratio of 70Z30 was obtained as the polymer (A).

10 parts by mass of the obtained (A) polymer and 90 parts by mass of polyethylene glycol (PEG400, manufactured by Lion Corporation) were kneaded at 90 ° C. for 90 minutes, and then spread into a sheet.

[Example 4A]

Methyl vinyl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN—169) Add 100 parts by weight of 3 parts by weight of water and hydrolyze at 90 ° C for 180 minutes As a result, a copolymer (molecular weight: 1.98 million) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a molar ratio of maleic anhydride Z maleic acid of 74Z26 was obtained as the polymer (A).

15 parts by mass of the obtained (A) polymer and 85 parts by mass of polyethylene glycol (PEG400, manufactured by Lion Corporation) were kneaded at 90 ° C. for 90 minutes, and then spread into a sheet.

[0047] (Example 5A)

Methyl vinyl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN—169) 100 mass%, add 2 mass% of water, and add 90 ° C. By hydrolyzing, a copolymer (molecular weight 1.98 million) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a molar ratio of maleic anhydride Z maleic acid of 77Z23 was obtained as (A) polymer. . 20 parts by mass of the obtained (A) polymer and 80 parts by mass of polyethylene glycol (PEG400, manufactured by Lion Corporation) were kneaded at 90 ° C. for 90 minutes, and then spread into a sheet.

[0048] (Example 6A)

Methyl beryl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN—169) 100 mass%, 2 mass% of water is added, and 90 ^o C By hydrolyzing, a copolymer (molecular weight: 1.98 million) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a molar ratio of maleic anhydride Z maleic acid of 84Z16 was obtained as (A) polymer. .

[0049] (Example 7A)

Methyl beryl ether Z Maleic anhydride Powered copolymer (ISP, GAN TREZ AN—139) 100 mass%, 20 mass% of water is added, and 90 ° C [Koo! By subjecting to partial hydrolysis, a copolymer (molecular weight 1.08 million) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a molar ratio of maleic anhydride to maleic anhydride of 17Z83 is obtained as the polymer (A). Obtained.

20 parts by mass of the obtained (A) polymer and 80 parts by mass of polyethylene glycol (PEG400, manufactured by Lion Corporation) were kneaded at 90 ° C. for 90 minutes, and then spread into a sheet.

[0050] (Example 8A)

Methyl beryl ether Z Maleic anhydride Powered copolymer (ISP, GAN TREZ AN—119) 100 mass%, 25 mass% water added, 20 ° C [Koo! By hydrolyzing, a copolymer (molecular weight 210,000) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a molar ratio of maleic anhydride Z maleic acid of 46Z54 was obtained as polymer (A). .

[0051] (Example 9A)

The obtained (A) polymer 3 parts by mass, hydroxypropylcellulose (HPC-H, Hercules) 10 parts by mass, and polyethylene glycol (PEG300, Lion Co.) 87 parts by mass for 90 minutes at 90 ° C After kneading, it was spread into a sheet.

[0052] (Example 10A)

Methyl beryl ether Z Maleic anhydride Power copolymer (ISP, GAN TREZ AN—139) 100 mass%, 15 mass% water added, 90 ° C By partial hydrolysis, (A) a polymer (molecular weight: 1.08 million) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a molar ratio of maleic anhydride Z maleic acid of 27Z73 is obtained. Obtained.

20 parts by mass of the obtained (A) polymer and 80 parts by mass of glycerin (manufactured by Nippon Shin-ryo Co., Ltd.) were kneaded at 90 ° C. for 120 minutes, and then spread into a sheet.

[0053] (Example 11 A)

10 parts by mass of the obtained (A) polymer and 90 parts by mass of polyglycerin (# 750, manufactured by Sakamoto Pharmaceutical Co., Ltd.) were kneaded at 90 ° C. for 90 minutes, and then spread into a sheet.

[0054] (Example 12A)

Methyl beryl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN—139) 100 mass%, 8 mass% water added, 90 ° C [Koo! By hydrolyzing, (A) the polymer is composed of maleic anhydride Z maleic acid molar ratio 56Z44 methyl vinyl ether Z maleic anhydride Z maleic acid A copolymer (molecular weight 1.08 million) was obtained.

(A) 25 parts by mass of the polymer, 45 parts by mass of propylene glycol (manufactured by Showa Denko KK), and 30 parts by mass of polyethylene glycol (PEG400, lion Corporation) were applied, and then 90 ° C for 90 minutes. Prepared by heating.

[Example 13 A]

The obtained (A) polymer 25 parts by mass, ethylene glycol (manufactured by Kanto Chemical Co., Ltd.) 23 parts by mass, dipropylene glycol (Showa Denko Co., Ltd.) 30 parts by mass, and polyethylene glycol (PEG400, Lion Corporation) 22 parts by mass were kneaded at 90 ° C for 90 minutes, and then spread into a sheet.

[0056] (Example 14A)

25 parts by mass of the obtained (A) polymer and 75 parts by mass of polyethylene glycol (PEG400, manufactured by Lion Corporation) were kneaded at 40 ° C. for 180 minutes, and then spread into a sheet.

[0057] (Comparative Example 1A)

Methyl beryl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN—139) Add 100 parts by weight of 1 part by weight of water and hydrolyze at 90 ° C for 180 minutes As a result, a copolymer having a molar ratio of maleic anhydride Z maleic acid of 87 Z13 and a methyl butyl ether Z maleic anhydride Z maleic acid power (molecular weight 1080,000) was obtained. 15 parts by mass of the obtained polymer and 85 parts by mass of polyethylene glycol (PEG400 Lion Co., Ltd.) were kneaded at 90 ° C. for 90 minutes, and then spread into a sheet.

[0058] (Comparative Example 2A)

Maleic anhydride Z Maleic anhydride with a molar ratio of maleic acid 14Z86 Z Maleic anhydride Z Maleic acid Copolymer (ISP, GANTREZ S-97, molecular weight 1.5 million) 20 parts by mass 80 parts by weight of polyethylene glycol (PEG400 Lion Co., Ltd.) was kneaded at 90 ° C for 90 minutes, and then spread into a sheet.

[0059] (Comparative Example 3A)

Methyl beryl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN-169) 100 mass%, 40 mass% water added, 90 ° C [Koo! By subjecting it to partial hydrolysis, a copolymer of maleic anhydride and maleic anhydride having a molar ratio of maleic acid and maleic acid of 11Z89,

980,000).

20 parts by mass of the obtained polymer and 80 parts by mass of polyethylene glycol (PEG400 Lion Co., Ltd.) were kneaded at 90 ° C. for 90 minutes, and then spread into a sheet.

[0060] (Comparative Example 4A)

Hydroxypropylcellulose (HPC-H, Nippon Soda Co., Ltd.) 10 parts by mass and polyethylene glycol (PEG400, Lion Co., Ltd.) 90 parts by mass were kneaded at 90 ° C for 90 minutes, then in sheet form Spread out.

[0061] Table 1 shows the evaluation results of Examples 1A to 14A and Comparative Examples 1A to 4A.

[0062] [Table 1]

1

[0063] As is apparent from the results in Table 1, Examples 1A to 14A were gel compositions having high tackiness and excellent gel-forming ability. The prepared patch was cut into 10 cm × 14 cm to evaluate skin irritation. The evaluation method was repeated on the inside of the forearm of five healthy panelists, and after 7 hours, and after 1 hour, the skin condition after 1 hour had passed. Observed. The score was 3 points: no change from before application, 2 points: a little reddish, 1 point: very reddish, and the average score of each panel was calculated. As a result, in Examples 1A to 14A, the average score is 2.5 points or more, there is no pain, the gel composition has low skin irritation, and no decrease in adhesiveness is observed after 7 hours of application. It was.

Comparative Examples 1A to 4A are expensive! Inability to achieve both cohesion and excellent gel-forming ability o

(Example 15 A)

The following composition was kneaded at 90 ° C for 90 minutes, and then spread into a sheet.

[0064] [Table 2] 3391 Table 2

[0065] In Example 15A, the patch had little skin irritation, high adhesiveness, and excellent gel-forming ability.

(Example 16 A)

[0066] [Table 3]

Three

[0067] In Example 16A, the patch had little skin irritation, high adhesiveness, and excellent gel-forming ability.

[0068] (Example 1B-: L0B) Further, after dissolving a medicinal component in polyhydric alcohol, a transdermal absorption enhancer was mixed, and a binder was dispersed and mixed to obtain a gel composition. The external preparation composition was applied onto the support so that the coating amount on the polyurethane film Z-knit laminated support was 0.7 (g / 70 cm ² ). After heat treatment, the patch was cut into a size of 7 cm x 10 cm in length x width. Example 1B ~: The components used in LOB are as follows.

(A) component

Methyl vinyl ether Z Maleic anhydride Copolymer (ISP, GAN TREZ AN—139) 100 mass%, 8 mass% of water added, 90 ° C [Koo! (A) As a polymer, a copolymer (weight average molecular weight 1,080,000) composed of methyl vinyl ether Z maleic anhydride Z maleic acid having a molar ratio of maleic anhydride Z maleic acid of 56Z44 was obtained. Obtained.

(B) component

PEG300: Polyethylene glycol (weight average molecular weight 300, manufactured by Lion Corp.) PEG400: Polyethylene glycol (weight average molecular weight 400, manufactured by Lion Corp.) PG: Propylene glycol (trade name "Propylene glycol PGjp", Arma Co., Ltd. EG: Ethylene glycol (trade name "Ethylene glycol (reagent)", Wako Pure Chemical Industries, Ltd.)

[Binder]

Hydroxypropylcellulose (weight average molecular weight 1 million, trade name “HPC—H”, manufactured by Nippon Soda Co., Ltd.)

[Transdermal absorption enhancer]

Jetyl sebacate: trade name “DES—SP”, manufactured by Nikko Chemicals Co., Ltd.

Diisopropyl adipate: trade name “DID”, manufactured by Nikko Chemicals Co., Ltd.

Isopropyl myristate: trade name “IPM—EX”, manufactured by Nikko Chemicals Co., Ltd. Ololeic acid: trade name “KOKOO”, manufactured by Higher Alcohol Industry Co., Ltd. Example 1B: Gel composition obtained from L0B Or use the patch and follow the method below

Then, a skin permeation test of medicinal components in the gel composition and an adhesive evaluation of the patch were performed. The results are shown in Table 4. <Skin penetration test>

Hos: Franz diffusion cell (applicable area: 4) 91cm).

A patch (Example 1B etc.) was laminated on the worn skin, and a sample in the cell was taken every unit time.

The collected samples were subjected to high performance liquid chromatography analysis, and the amount of each medicinal component that permeated through the skin after 2 hours (medicinal component skin permeation amount, μg / cm ² ) was determined.

A large amount of medicinal component skin permeation after 2 hours means that the initial percutaneous absorption is excellent.

To express. In this evaluation system, if the medicinal component skin permeation amount after 2 hours is 0.5 / z gZcm ² or more, the initial

Excellent percutaneous absorption.

Example 1B: The adhesiveness of the patch prepared with L0B was evaluated based on the ball tack value when measured at an inclination angle of 30 ° according to the JIS Z-0237 test.

[Table 4]

JP2006 / 303391

Table 4

Real life

IB 2B 3B 4B 5B

(A) Component 15 15 15 15 15

(B) Component

PEG300 5 10 40 5 5

PEG400 5 10 13 5 S

PG 40 13 40 40

EG 13 10 13 13 Binder

Hydroxypropylcellulose 10 10 10 10 10 Vegetables

Lindamecin 2 2 2 2 2 Transdermal absorption enhancer

Jetinore sebacate 10 30 20

Diisopropinole adipate 10 Isopropyl myristate 10

Example

6B 7B 8B 9B 10B

(A) Component 15 15 15 15 15

(B) Component

PEG300 5 5 5 10

PEG shelf 5 5 10 5 10

PG 40 40 40

EG 13 13 40 53 Dipropylene glycolate 13 13 Binder

Hydroxypropinoresenorelose 10 10 10 10 10 Drug

Indomethacin 2 2 2 2 Felbinac 2

Diameter absorption enhancer

Seno ί Jetinore cinnamate 10 10 10 Diisopropinole adipate 10

Oleate oleate 10

Permeation rate of medicinal component after 2 o'clock closing (ng / cm ² ) 1. 2 2. 4 1. 2 1. 3 1. 8 Adhesiveness ◎ © ◎ ◎ ◎

Claims

The scope of the claims

[1] (A) a repeating unit composed of at least one unsaturated moiety and an acid anhydride moiety, and at least one unsaturated moiety and an acid compound moiety corresponding to the acid anhydride moiety A gel composition comprising a polymer containing units and (B) a polyhydric alcohol,

(A) The gel composition, wherein the polymer contains an acid anhydride part and an acid compound part corresponding to the acid anhydride part in a molar ratio of 15Z85 to 85Z15.

[2] The gel composition according to claim 1, wherein (A) at least one unsaturated portion is a vinyl compound, and the acid anhydride portion is selected from the group strength of maleic anhydride portion and itaconic anhydride partial force.

[3] (A) Polymer strength C3-C24 alkyl butyl ether Z Maleic anhydride Copolymer composed of maleic acid, C3-C24 alkyl vinyl ether Z Itaconic anhydride Z Itaconic acid The gel composition according to claim 2, wherein the gel composition is selected from the group consisting of copolymers.

[4] The copolymer power composed of alkyl butyl ether having 3 to 24 carbon atoms, Z maleic anhydride, and maleic acid. 4. The copolymer is composed of methyl vinyl ether, Z maleic anhydride, and maleic power. Gel composition.

[5] (A) The molar specific power of the acid anhydride part in the polymer and the acid compound part corresponding to the acid anhydride part is 20Z80 to 70Z30! Gel composition.

[6] (B) The polyhydric alcohol is 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, diglycerin, triglycerin, polyglycerin, diethylene glycol, dipropylene glycol, triethylene glycol, polyethylene glycol, The gel composition according to any one of claims 1 to 5, which is selected from the group consisting of polypropylene glycol, polyethylene / polypropylene glycol, polyoxyethylene hydrogenated castor oil and sorbitol.

[7] (B) Polyhydric alcohol power The power according to any one of claims 1 to 5, wherein the polyhydric alcohol mixture is a dihydric to hexahydric alcohol mixture containing polyethylene glycol having a weight average molecular weight of 200 to 2000. Gel composition.

[8] The gel composition according to any one of claims 1 to 7, wherein (A) the polymer and (B) the polyhydric alcohol are contained in a mass ratio of 1Z99 to 55Z45.

[9] The gel composition according to any one of claims 1 to 8, further comprising a binder.

[10] The binder according to claim 9, wherein the binder is at least one selected from the group force of carboxybule polymer, alginic acid, polybulal alcohol, polyvinylpyrrolidone, carboxymethylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose. Gel composition.

[11] The gel composition according to any one of claims 1 to 10, further comprising a medicinal component.

[12] Further, the following formula (1):

(R ² OOC)-R ¹ -R ³ (1)

[Wherein R ¹ is a hydrocarbon group having 3 to 36 carbon atoms, R ² is a hydrocarbon group having 1 to 20 carbon atoms, R ³ is a hydrogen atom or —COOR ⁴ (R ⁴ is 1 carbon atom ~: Is a hydrocarbon group of LO) o]

The gel composition according to any one of claims 1 to 11, comprising a transdermal absorption enhancer represented by the formula:

[13] The ester power group consisting of cetyl sebacate, diisopropyl sebacate, dimethyl adipate, diisopropyl adipate, oleyl oleate, isopropyl myristate, isopropyl palmitate, ethyl linoleate and isopropyl linoleate 13. The gel composition according to claim 12, wherein the gel composition is at least one selected from force.

[14] The gel composition according to any one of claims 1 to 13, which does not contain a crosslinking agent.

[15] An adhesive agent obtained by spreading the gel composition according to any one of claims 1 to 14 on a support.

[16] (a) A polymer containing a repeating unit composed of at least one unsaturated moiety and an acid anhydride moiety is hydrolyzed to form an acid anhydride moiety and an acid anhydride moiety contained in the polymer. The corresponding acid compound part is in a molar ratio of 15Z85 to 85Z15 (A) a repeating unit composed of at least one unsaturated part and an acid anhydride part, and at least one unsaturated part And an acid compound portion corresponding to the acid anhydride portion. Obtaining a polymer comprising units,

A step of dissolving the obtained (A) polymer in (B) a polyhydric alcohol, and a step of heating the resulting mixture in the absence of a crosslinking agent;

A method for producing a gel composition, comprising: