JPH07187999A - Pressure-sensitive adhesive, medical cataplasm preparation prepared by using the same adhesive and its production - Google Patents

Abstract

PURPOSE:To obtain a cataplasm remarkably low in irritation to the skin, further having other properties required for a medical cataplasm and, therefore, remarkably useful as a medical cataplasm. CONSTITUTION:A pressure-sensitive adhesive and a medical cataplasm involving a substrate layer and an adhesive layer composed of this pressure-sensitive adhesive containing medicinal components. The characteristic of this pressure- sensitive adhesive is that it is produced by using a polymer synthesized by copolymerizing (a) 0.1 to 80wt.% monomer represented by the formula CH2=CR1 CO(OC2H4)nOR2 [R1 and R2 are each H or a 1 to 4C alkyl group; (n) is an integer of 1 to 23], (b) 19.9 to 99.8wt.% alkyl (meth)acrylate (the number of carbons in the alkyl group is 1 to 10), (c) 0.01 to 10wt.% unsaturated monomer having two or more polymerizable groups capable of radical polymerization and having mutually different reactivities in the molecule and (d) 0 to 40wt.% ethylenic unsaturated monomer copolymerizable with (a) to (c) [provided that (a)+(b)+(c)+(d)=100wt.%] as the main component and photo-crosslinking it.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an adhesive, a medical patch using the same, and a method for producing the same. Since the pressure-sensitive adhesive of the present invention is extremely hypoallergenic and has other properties required for the pressure-sensitive adhesive, it can be widely used in medical patch preparations.

[0002]

2. Description of the Related Art Conventionally, a patch preparation containing a drug in an adhesive layer has been applied to the surface of the skin to allow the drug to be absorbed into the body through the skin. Such a patch preparation for percutaneous absorption can avoid the first-pass effect in the liver upon oral administration, and can control the permeation amount of the drug so as not to cause an excess or deficiency of the dose over a long period of time. It has advantages such as long-term continuous administration and easy discontinuation of administration. Various acrylic adhesives and rubber adhesives have been developed as adhesives that form the adhesive layer of such patch preparations, but conventional adhesives have too strong an adhesive force to the skin and are not used after use. When the preparation was peeled from the skin, in addition to giving pain due to physical irritation and peeling a part of the stratum corneum, skin irritation was often caused. In order to solve these problems, copolymerization of a (meth) acrylate monomer and a hydrophilic monomer and blending of an acrylic polymer and a (co) polymer of a hydrophilic monomer have been carried out.

For example, in Japanese Patent Laid-Open No. 4-266818,
A technique is disclosed in which a blending polymer of a vinylpyrrolidone (co) polymer and a (meth) acrylic acid copolymer contains a softening agent to reduce skin irritation. However, since it is a blended polymer, it has poor compatibility and lacks stability as a formulation, and N-vinyl-2-pyrrolidone lacks the ability to absorb perspiration from the skin, so it is easy to cause irritation. It was In addition, special table Sho-60-50099
No. 2 includes an acrylic acid ester monomer, a hydrophilic monomer such as an alkylene oxide group-containing (meth) acrylate, an ethylenically unsaturated carboxylic acid, acrylamide, and N.
-Copolymerized with a polar monomer such as vinyl-2-pyrrolidone, but lacks cohesion because it is not crosslinked,
Moreover, when ethylenically unsaturated carboxylic acid is used, it cannot be used in a percutaneous absorption preparation of a basic drug because it interacts with the basic drug.

[0004]

Therefore, the present invention solves the above-mentioned problems of the prior art and has extremely low skin irritation and other properties such as adhesive strength and cohesive strength. An object is to provide such an adhesive, a medical patch preparation using the same, and a method for producing the same.

[0005]

Means for Solving the Problems The present invention has been studied as to a pressure-sensitive adhesive containing an acrylic copolymer as a main component, and as a result, a copolymer obtained from a combination of specific monomers in a specific amount was obtained. The inventors have found that a pressure-sensitive adhesive obtained by photocrosslinking can achieve the object of the present invention, and completed the present invention. That is, the present invention provides (a) the general formula CH ₂ = CR ₁ CO (OC ₂ H ₄ ) _n OR ₂ (I) (wherein R ₁ and R ₂ may be the same or different,
And (b) an alkyl (meth) acrylate, each of which represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents an integer of 1 to 23). Ester (alkyl group has 1 to 10 carbon atoms) 19.9 to 99.8% by weight; (c) Unsaturated monomer having two or more radically polymerizable polymerizable groups having different reactivity in the molecule 0.01 to 10% by weight; and (d) an ethylenically unsaturated monomer copolymerizable with the above (a), (b) and (C) (however, excluding ethylenically unsaturated carboxylic acid) 0 -40% by weight (however, (a) +
(B) + (c) + (d) = 100% by weight] to obtain a polymer, and photocrosslink this to provide a pressure-sensitive adhesive.

The present invention also provides a medical patch comprising a support layer and an adhesive layer containing a drug, wherein the adhesive in the adhesive layer is the above-mentioned adhesive. provide. Furthermore, the present invention provides a method for producing the polymer by copolymerizing the monomers (a) to (d) to obtain a polymer, and photocrosslinking the polymer to produce the pressure-sensitive adhesive of the present invention. In the production method of the present invention, the light used in the photocrosslinking step is 3
It is a visible light from 60 nm to 550 nm, and it is desirable to use a photosensitizer. Hereinafter, the pressure-sensitive adhesive of the present invention and the medicated patch preparation using the same will be described in detail.

Examples of the monomer represented by the general formula (I) in (a) above include hydroxyethyl (meth) acrylate, methoxyethyl (meth) acrylate, ethoxyethyl (meth) acrylate, butoxyethyl (meth). ) Acrylate, hydroxydiethylene glycol (meth) acrylate, hydroxypolyethylene glycol (meth) acrylate, methoxydiethylene glycol (meth) acrylate, methoxypolyethylene glycol (meth) acrylate, ethoxydiethylene glycol (meth) acrylate, ethoxypolyethylene glycol (meth) acrylate, butoxydiethylene glycol Examples thereof include (meth) acrylate and butoxy polyethylene glycol (meth) acrylate. Among these, hydroxy polyethylene glycol (meth) acrylate, methoxy polyethylene glycol (meth) acrylate and ethoxy polyethylene glycol (meth) acrylate are preferable. Such a monomer (a) is an essential component for enhancing the water absorbency of the copolymer and maintaining the low irritation to the skin, and it is used alone or in combination of two or more. You may use it in combination. The amount of the monomer (a) used is 0.1 to 80% by weight, preferably 5 to 50% by weight based on the weight of all the monomers (a) to (d).
% By weight, and if less than 0.1% by weight, water absorption is poor,
If it exceeds 80% by weight, the cohesive force is lowered, which is not preferable.

Examples of the (meth) acrylic acid alkyl ester (b) (wherein the alkyl group has 1 to 10 carbon atoms) include, for example, methyl (meth) acrylate, (meth)
Ethyl acrylate, n-propyl (meth) acrylate,
Iso-propyl (meth) acrylate, n-butyl (meth) acrylate, iso-butyl (meth) acrylate, tert-butyl (meth) acrylate, n- (meth) acrylate
Amyl, iso-amyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, octyl (meth) acrylate, iso-nonyl (meth) acrylate, decyl (meth) acrylate and 2-hydroxypropyl (meth) acrylate and the like can be mentioned. Among these, ethyl acrylate and acrylic acid n
-Butyl, 2-ethylhexyl acrylate and methyl methacrylate are preferred. Such a monomer (b) is an essential component for the copolymer to have suitable tackiness, and may be used alone or in combination of two or more. The amount of the monomer (b) used is 19.9 to 99.8% by weight, preferably 30 to 95% by weight, based on the weight of all the monomers (a) to (d). If it is less than 9% by weight, suitable adhesiveness cannot be obtained, and it is 99.8% by weight.
When it exceeds, the components (a) and (c) decrease relatively,
As a result, the water absorption and the cohesive force decrease, which is not preferable.

Examples of the unsaturated monomer having two or more radically polymerizable polymerizable groups having different reactivities in the molecule (c) include, for example, isoprene and 2-chloro-1,3-.
Aliphatic conjugated dienes such as butadiene (excluding 1,3-butadiene); vinyl (meth) acrylate, allyl (meth) acrylate, vinyl cinnamate, allyl cinnamate, cinnamyl cinnamate and cinnamate cis -3-hexenyl etc. are mentioned. Of these, allyl (meth) acrylate and vinyl cinnamate are preferable. Such a monomer (c) is an essential component for the copolymer to have an appropriate cohesive force, and may be used alone or in combination of two or more. The amount of the monomer (c) used is 0.0 based on the weight of all the monomers (a) to (d).
1 to 10.0% by weight, preferably 0.01 to 3% by weight, and if less than 0.01% by weight, an appropriate cohesive force cannot be obtained,
If it exceeds 10.0% by weight, the adhesive strength is lowered, which is not preferable.

Examples of the ethylenically unsaturated monomer copolymerizable with (a), (b) and (C) in (d) above include 1,3-butadiene; styrene and α-methyl. Aromatic vinyl compounds such as styrene, vinyltoluene and ethylvinylbenzene; (meth) acrylamide, N-
Alkyl amides of ethylenically unsaturated carboxylic acids such as methylol acrylamide; carboxylic acid vinyl esters such as vinyl acetate and vinyl propionate; amino of ethylenically unsaturated carboxylic acids such as aminoethyl acrylate, dimethylaminoethyl acrylate and butylaminoethyl acrylate Alkyl esters; aminoalkylamides of ethylenically unsaturated carboxylic acids such as aminoethylacrylamide, dimethylaminomethylmethacrylamide, methylaminopropylmethacrylamide; vinyl cyanide compounds such as (meth) acrylonitrile, α-chloroacrylonitrile; glycidyl ( Unsaturated aliphatic glycidyl esters such as (meth) acrylate; N-vinyl-2-pyrrolidone, methylvinylpyrrolidone, vinylpyridine, vinylpyrazine, bi Le pyrimidine, vinyl piperazine,
Examples thereof include vinylpyrrole and vinyloxazole. Among these, N-vinyl-2-pyrrolidone is preferable. Ethylenically unsaturated carboxylic acids are not preferred because they interact with basic medicinal ingredients.

The monomer (d) may be used alone or in combination of two or more, and the amount thereof used is based on the weight of all the monomers (a) to (d). 0-4
0.0% by weight, preferably 0 to 30% by weight, 40
When the content is more than weight%, the adhesive strength is lowered, which is not preferable. The total amount of (a), (b), (c) and (d) is 100% by weight. In the present invention, by adopting the above-mentioned monomers (a) to (d) and the above-mentioned usage amounts thereof, it is possible to achieve the object of the present invention of being mild to the skin. is there.

The method for producing the pressure-sensitive adhesive of the present invention will be described below. The production method of the present invention comprises a method of copolymerizing the monomers (a) to (d) to obtain a polymer, and photocrosslinking the polymer to produce the pressure-sensitive adhesive of the present invention. The polymerization method in the production method of the present invention is not particularly limited,
Any of thermal polymerization, photopolymerization, and radiation polymerization may be used, and methods such as bulk polymerization, solution polymerization, suspension polymerization, and emulsion polymerization can be adopted, but solution polymerization by thermal polymerization is preferable in terms of production. Hereinafter, the solution polymerization by the thermal polymerization will be described as an example. Solution polymerization is generally carried out by charging a monomer, an organic solvent, a polymerization initiator and, if necessary, a chain transfer agent, and heating and stirring in a nitrogen stream for several hours. In this case, the monomer, organic solvent, polymerization initiator and / or chain transfer agent is
It may be charged all at once before the reaction, or may be added all at once and / or continuously during the reaction.

Examples of the organic solvent which can be used in the method of the present invention include aromatic hydrocarbons such as benzene, toluene and xylene; n-hexane, n-heptane, n-octane, n-decane and petroleum. Aliphatic or alicyclic hydrocarbons such as spirit, petroleum naphtha and turpentine oil; alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, iso-propyl alcohol, n-butyl alcohol; ethyl acetate,
esters such as n-butyl acetate, n-amyl acetate, cellosolve acetate, butyl cellosolve acetate; ethers such as methyl cellosolve, ethyl cellosolve, butyl cellosolve; and ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone; be able to. However, the pressure-sensitive adhesive of the present invention and medical patch preparations using the same are solvent-free so as not to contain a solvent that becomes an irritant to the skin, and therefore an organic solvent is added from the obtained copolymer solution. Need to be volatilized. Therefore, among the above organic solvents, it is more preferable to use one having a boiling point of 50 to 150 ° C., and it is particularly preferable to use methyl alcohol, n-propyl alcohol, ethyl acetate, n-hexane, acetone, methyl ethyl ketone, or the like. These organic solvents may be used alone or in combination of two or more.

Further, in order to achieve the object of the present invention of reducing the unreacted residual monomer in the copolymer which is a stimulant to the skin as much as possible, in the production method of the present invention,
Various known methods can be adopted. For example,
A method such as adding a polymerization initiator in the middle of the polymerization reaction, raising the polymerization temperature in the latter half of the polymerization reaction, and taking a sufficient aging time in the latter half of the polymerization reaction can be suitably adopted.
After the completion of the reaction, the residual monomer can be removed by precipitating the copolymer in a poor solvent.

The polymerization initiator which can be used in the polymerization method of the present invention may be any one, for example, an organic peroxide such as benzoyl peroxide, lauroyl peroxide, methyl ethyl ketone peroxide; 2 , 2'-azobis-iso-butyronitrile, 2,2'-azobis-2,4-dimethylvaleronitrile and the like azo compounds and the like. These are used alone or in combination of two or more. can do. The amount of the polymerization initiator used is 0.01 to 0.5 parts by weight, particularly 0.02 to 100 parts by weight of the monomer.
It is preferably 0.3 part by weight. Examples of chain transfer agents that can be used in the polymerization method of the present invention include halogenated hydrocarbons such as chloroform and bromoform; mercaptans such as n-dodecyl mercaptan; terpenes such as dipentene and terpinolene;
Aromatic compounds such as anthracene and phenanthrene; p
-Aromatic nitro compounds such as nitroaniline and nitrobenzene. The amount of the chain transfer agent used is preferably 0.005 to 2.0 parts by weight based on 100 parts by weight of the monomer. The copolymerization reaction is generally 30 to
It is desirable to carry out in the temperature range of 150 ° C, preferably 60 to 120 ° C.

Further, a reaction inhibitor or a reaction inhibitor may be added during the reaction or after the reaction, and examples thereof include hydroquinone and hydroquinone monomethyl ether. The amount of such a reaction inhibitor or reaction inhibitor used is preferably 0.001 to 5% by weight, and particularly preferably 0.01 to 1% by weight, based on the copolymer. The pressure-sensitive adhesive of the present invention is obtained by photocrosslinking the polymer obtained as described above. At this time, it is preferable to add a photosensitizer in order to accelerate the crosslinking reaction. Examples of the photosensitizer include camphorquinone,
Examples thereof include benzophenone, methyl o-benzoylbenzoate, benzoin ethyl ether, 2-ethylanthraquinone and benzyl, and among them, camphorquinone and benzophenone are preferable. When the photosensitizer is used, its amount is preferably 0.05 to 2 parts by weight based on 100 parts by weight of the copolymer.

The light irradiation is preferably carried out in the absence of oxygen. As the light source, various conventional light sources can be used. The wavelength is 360 to 550 nm, particularly 400 to 500 in consideration of the decomposition of the medicinal component and the photocrosslinking rate.
Visible light of nm is desirable. By performing photo-crosslinking in this way, it is easy to control the crosslink density, and it is also suitable for drug components that are weak to heat, and even at low temperatures,
It is possible to eliminate the solvent when coating the adhesive.

The medicinal component that can be incorporated into the adhesive or the medicated patch of the present invention may be any drug as long as it is a drug that can be percutaneously absorbed. For example, hypnosis / sedation. Agents (nitrazebum, barbital, etc.),
Antipyretic and anti-inflammatory analgesics (ketoprofen, indomethacin, ketorolac, loxoprofen, denidap, etc.), excitement /
Stimulants (methamphetamine, bemeglide, etc.), neuropsychiatric agents (meprobamate, imipramine, etc.), local anesthetics (lidocaine, procaine, etc.), skeletal muscle relaxants (tizanidine, eperisone, dantrolene, cyclobenzaprine, etc.), agents for autonomic nerves (Carpronium, neostigmine, etc.), anti-Parkinson's agent, antihistamine (mequitazine, diphenhydramine, etc.), cardiotonic agent (digoxin, aminophylline, etc.), antihypertensive agent (nifedipine, alprenolol, atenolol, etc.), coronary vasodilator (nitroglycerin) , Isosorbide nitrate, etc., peripheral vasodilators (nicamethate, cyclandate, etc.), agents for circulatory organs (flunarizine, ibudilast, etc.), antitussive expectorants (tranilast, tulobuterol, etc.), anti-vertigo agents (betahistine, difenidol, etc.) , Drugs (buprenorphine,
Morphine, fentanyl, etc.), corticosteroids (testosterone, etc.), follicular progesterone agents (estradiol, estriol, etc.), bactericidal and disinfectant for external skin, wound protector, purulent disease external preparation (kanamycin, etc.), parasitic skin Disease agents (miconazole etc.) etc. are mentioned. These medicinal components may be used singly or in combination of two or more kinds, and with respect to 100% by weight of the copolymer,
It is preferably used in the range of 0.001 to 40% by weight, particularly 0.01 to 30% by weight.

Further, in the pressure-sensitive adhesive or medical patch of the present invention, any known absorption promoter can be added for the purpose of better absorbing the above-mentioned medicinal components. Examples of such absorption promoters include dimethyl sulfoxide, sorbitol, urea, diethyl adipate, squalene, squalane, acetylated lanolin, lanolinic acid, lanolin alcohol, petrolatum, camphor, sodium lauric acid, higher fatty acid triglyceride, Polyoxyalkylene glycol, fatty acid monoethanolamide, ethylene glycol monoethyl ether, polyoxypropylene alkyl ether, Azone,
Pyrothiodecane, geraniol, eugenol, timolol, l-menthol, d-limonene, lauryl alcohol, myristyl alcohol, oleyl alcohol, n
-Capric acid, n-caproic acid, myristic acid, palmitic acid, cetyl palmitate, methyl cinnamate, isopropyl myristate, monolaurin, monoolein, salicylic acid, methyl salicylate, glycol salicylate,
Examples thereof include crotamiton, and these can be used alone or in combination of two or more. The amount of this absorption promoter used is 0.1 with respect to the copolymer.
It is preferably from 01 to 50% by weight, particularly from 0.1 to 30% by weight.

Further, in the pressure-sensitive adhesive or medical patch of the present invention, a solubilizer may be added, if necessary, in order to promote uniform dispersion of the medicinal component in the base material. Examples of the solubilizer include isopropyl myristate, myristyl myristate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, decyl oleate, hexyldecyl dimethyloctanoate, higher fatty acid esters such as hexyldecyl, and polyoxy. Examples thereof include polyoxyether alkyl ethers such as ethylene lauryl ether and polyoxyethylene oleyl ether, polyoxyethylene nonylphenyl ethers, polyoxyethylene alkylphenyl ethers such as polyoxyethylene octylphenyl ether, crotamiton and liquid paraffin. The amount of the solubilizer used is preferably 0.01 to 30% by weight, more preferably 0.1 to 20% by weight, based on the copolymer.

Further, in the pressure-sensitive adhesive or medical patch of the present invention, a moisturizer can be added, if necessary, and examples of the moisturizer include ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol. , Trimethylene glycol, dipropylene glycol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, hexanediol, neopentyl glycol, dibrom neopentimglycol And water-soluble polyhydric alcohols such as trimethylmenthanediol, trimethylolethane, trimethylolpropane, pentaerythritol, dipentaerythritol, glycerin, diglycerin, and sorbitol. The amount of moisturizer used is
0.01-30% by weight, especially 0.1-0.1%, based on the copolymer
It is preferably 20% by weight. Further, in the pressure-sensitive adhesive or medical patch of the present invention, known additives such as ultraviolet absorbers, antioxidants, preservatives, inorganic fillers and the like can be added, if necessary.

As the ultraviolet absorber, for example, known p
-Aminobenzoic acid derivative, anthranilic acid derivative, coumarin derivative, amino acid derivative, benzotriazole derivative, tetrazole derivative, imidazoline derivative, pyrimidine derivative, dioxatin derivative, furan derivative, pyrone derivative, camphor derivative, nucleic acid derivative, allantoin derivative, nicotinic acid derivative, Examples include shikonin and vitamin 6 derivatives. The amount of the ultraviolet absorber used is 0.01 to 10% by weight, particularly 0.1 to 5% by weight, based on the copolymer.
Is preferred. Examples of the antioxidant include ascorbic acid, stearic acid ester, sodium ascorbate, tocopherol (α-tocopherol, β
-Tocopherol, γ-tocopherol, δ-tocopherol, etc. d-form, l-form, dl-form) and ester derivatives thereof, nordihydroguaselethetic acid, dibutylhydroxytoluene, butylhydroxyanisole, tert-butylhydroxynongallic acid ester (Ester such as ethyl, propyl and isoamyl), 1-oxo-3methyl-4-isopropylbenzene and the like. The amount of the antioxidant used is preferably 0.01 to 5 parts by weight, particularly 0.1 to 3% by weight, based on the copolymer.

Examples of preservatives include benzoic acid, sodium benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, and the like, and the amount thereof is 0.01 with respect to the copolymer. ~ 3
It is preferable that the content is parts by weight, particularly 0.1 to 2% by weight.
Examples of the inorganic filler include zinc white, calcium carbonate, titanium dioxide, silica and the like, and the amount thereof is 0.1 to 20% by weight, particularly 0.5 to 0.5, with respect to the copolymer.
It is preferably 10% by weight. The medicated patch preparation of the present invention is characterized by having a pressure-sensitive adhesive layer made of the pressure-sensitive adhesive of the present invention, and other layers and materials constituting those layers may be of any known type. Good.

[0024]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. In the examples, “parts” and “%” indicating proportions are based on weight. Further, the skin irritation in Examples and Comparative Examples was measured by the following method. (Skin irritation test) The patch preparation for medical use obtained in each Example and each Comparative Example was applied to the upper back of 30 healthy adult males.
Attached for 8 hours. The degree of skin contact of each person was evaluated 30 minutes and 24 hours after peeling. In addition, the skin contact condition used as a criterion is as follows. -: No change ±: Weak redness +: Clear redness ++: Serious feeling

Example 1 In a separable flask equipped with a reflux condenser, a thermometer, a stirrer, and a nitrogen gas introduction device, 100 parts of ethyl acetate and azobisisobutyronitrile (A
IBN) (0.05 parts) was added to make a uniform solution, and the monomer components shown in the following Table 1 were added thereto, followed by heating and stirring. While introducing nitrogen gas, the internal temperature of the separable flask was adjusted to 70 to 80 ° C., polymerization was performed for 2 hours, then cooled to 25 ° C., the reaction was completed, and the solid content concentration was about 50. A copolymer solution of wt% was obtained. Polymerization conversion rate is 9
It was 9% or more. To this copolymer solution, 1% by weight of canfaquinone and 10% by weight of ketoprofen were added, and the mixture was stirred so as to be uniform. It was applied on a thick PET film and dried sufficiently in an oven. Visible light was irradiated from a distance of 30 cm on the surface of this pressure-sensitive adhesive layer with a high-pressure mercury lamp equipped with a filter that blocks wavelengths of 360 nm or less, and after photocrosslinking, the pressure-sensitive adhesive surface was used as a liner for release treatment. Stick the PET film to
It was punched into a size of cm ² (5 × 6 cm) to obtain a medical patch preparation of the present invention. The obtained medicated patch was excellent in tackiness, skin adhesion, water absorption and drug release. Also,
The results of the skin irritation test of this patch preparation are shown in Table 2 below.

Examples 2 and 3 and Comparative Examples 1 to 3 In the same manner as in Example 1, except that the charged amounts of various monomers were changed as shown in Table 1 below, the pressure-sensitive adhesive and A medicated patch preparation was obtained. The patch preparations obtained in Examples 2 and 3 were excellent in tackiness, skin adhesiveness, water absorption, and drug component release. The results of the skin irritation test of the patch preparations obtained in Examples 2 and 3 and Comparative Examples 1 to 3 are shown in Table 2 below.

Example 4 An adhesive and a medicated patch preparation of the present invention were obtained in the same manner as in Example 1, except that the drug incorporated in Example 1 was changed to isosorbide dinitrate. The obtained patch preparation is
It was excellent in tackiness, skin adhesion, water absorption, and release of medicinal components. The results of the skin irritation test of this patch preparation are shown in Table 2 below. Example 5 A pressure-sensitive adhesive and a medicated patch preparation of the present invention were obtained in the same manner as in Example 1, except that the compounded drug in Example 1 was changed to morphine. The obtained patch preparation is adhesive,
It was excellent in skin adhesion, water absorption, and release of medicinal ingredients. The results of the skin irritation test of this patch preparation are shown in Table 2 below.

[0028]

Table 1 Examples Comparative Examples ------------------ Component ----- Component 1 2 3 4 5 1 2 3 ----------- −−−−−−−−−−−−−−−−−−−−−−− (Monomer component) (a) Hydroxy polyethylene glycol # 400 acrylate 20 40-20 20-90 20 Methoxy polyethylene Glycol # 1000 acrylate--20-----(b) Ethyl acrylate 9.9 9.9 5 9.9 9.9 29.9-10 2-Ethylhexyl acrylate 50 40 50 50 50 50 9.9 50 Methacrylic acid--5----- (C) Allyl methacrylate 0.1-0.1 0.1 0.1 0.1 0.1-Vinyl cinnamate-0.1------(d) N-vinyl-2-pyrrolidone 20 10 20 20 20 20-20 (Pharmaceutical ingredient) Ketoprofen 10 10 10--10 10 10 Isosorbide dinitrate---10----Morphine----10------------------------------ −−−−−−−−−−−−−−−−

[0029]

Table 2 Examples Comparative Examples Skin irritation test -------------------- (Positive rate) (%) 1 2 3 4 5 1 2 3 --- −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− After 30 minutes ± or more ± 0 0 0 0 0 0 10.0 0 3.3 + or more 0 0 0 0 0 6.7 0 0 0 After 24 hours ± or more 0 0 0 0 0 0 6.7 3.3 3.3 + or more 0 0 0 0 0 0 0 0 0 0 −−−−−−−−−−−−−−−−−−−−−−− −−−−−−−−−−−−−−

As shown in Table 2, it is clear that the medical patch preparation of the present invention obtained in each of Examples 1 to 5 has extremely low irritation. On the other hand, Comparative Example 1
It is clear that the medical patch preparation containing the acrylic copolymer as the main component obtained in each of 3 to 3 has a significantly larger irritation to the skin than the present invention and is inferior as a medical patch preparation.

[0031]

EFFECTS OF THE INVENTION The adhesive of the present invention and the medicated patch preparation using the same are much more effective on the skin than the conventional acrylic copolymer-based adhesive and the medical patch preparation using the same. It is hypoallergenic and also has other properties required for adhesives, such as adhesive strength and cohesive strength, and is suitable for the compounding of basic drugs. It is extremely useful as a patch preparation.

Claims (8)

[Claims] 1. (a) General formula CH ₂ ═CR ₁ CO (OC ₂ H ₄ ) _n OR ₂ (I) (wherein R ₁ and R ₂ may be the same or different,
And (b) an alkyl (meth) acrylate, each of which represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents an integer of 1 to 23). Ester (alkyl group has 1 to 10 carbon atoms) 19.9 to 99.8% by weight; (c) Unsaturated monomer having two or more radically polymerizable polymerizable groups having different reactivity in the molecule 0.01 to 10% by weight; and (d) an ethylenically unsaturated monomer copolymerizable with the above (a), (b) and (C) (however, excluding ethylenically unsaturated carboxylic acid) 0 -40% by weight (however, (a) +
(B) + (c) + (d) = 100% by weight], which is obtained by photocrosslinking a polymer obtained by copolymerizing the polymer as a main component. 2. The monomer (a) is hydroxyethyl (meth) acrylate, methoxyethyl (meth) acrylate, ethoxyethyl (meth) acrylate, butoxyethyl (meth) acrylate, hydroxydiethylene glycol (meth) acrylate, Hydroxy polyethylene glycol (meth) acrylate, methoxydiethylene glycol (meth) acrylate, methoxypolyethylene glycol (meth) acrylate, ethoxydiethylene glycol (meth) acrylate, ethoxypolyethylene glycol (meth) acrylate, butoxydiethylene glycol (meth) acrylate or butoxypolyethylene glycol (meth ) The pressure-sensitive adhesive according to claim 1, which is an acrylate. 3. The (meth) acrylic acid alkyl ester of (b) (wherein the alkyl group has 1 to 10 carbon atoms).
Is methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, iso-propyl (meth) acrylate, n-butyl (meth) acrylate, iso (meth) acrylate- Butyl, tert-butyl (meth) acrylate, n-amyl (meth) acrylate,
Iso-amyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate,
Octyl (meth) acrylate, iso (meth) acrylate
-Nonyl, decyl (meth) acrylate or 2-hydroxypropyl (meth) acrylate, The pressure-sensitive adhesive according to claim 1 or 2. 4. The unsaturated monomer having at least two radically polymerizable polymerizable groups having different reactivities in the molecule (c) is an aliphatic monomer such as isoprene or 2-chloro-1,3-butadiene. Conjugated dienes (excluding 1,3-butadiene); vinyl (meth) acrylate, allyl (meth) acrylate, vinyl cinnamate, allyl cinnamate, cinnamyl cinnamate or cis-3-hexenyl cinnamate. Claims 1-3
The adhesive according to any one of 1. 5. (a), (b) and (c) of (d) above
The ethylenically unsaturated monomer copolymerizable with
3-Butadiene; Aromatic vinyl compounds such as styrene, α-methylstyrene, vinyltoluene, ethylvinylbenzene; Alkylamides of ethylenically unsaturated carboxylic acids such as (meth) acrylamide, N-methylolacrylamide; Vinyl acetate, propionic acid Carboxylic acid vinyl esters such as vinyl; aminoalkyl esters of ethylenically unsaturated carboxylic acids such as aminoethyl acrylate, dimethylaminoethyl acrylate, butylaminoethyl acrylate; aminoethyl acrylamide, dimethylaminomethyl methacrylamide, methylaminopropyl methacrylamide, etc. Ethylenically unsaturated carboxylic acid aminoalkylamides; vinyl cyanide compounds such as (meth) acrylonitrile, α-chloroacrylonitrile; glycidyl (meth) acryloyl Unsaturated aliphatic glycidyl ester such as acrylate; N-vinyl-2-pyrrolidone, methylvinylpyrrolidone, vinylpyridine, vinylpyrazine, vinylpyrimidine, vinylpiperazine, vinylpyrrole or vinyloxazole. Adhesive described. 6. A medical patch preparation comprising a support layer and an adhesive layer containing a drug, wherein the adhesive in the adhesive layer is the adhesive according to any one of claims 1 to 5. The medical patch according to the above. 7. (a) General formula CH ₂ ═CR ₁ CO (OC ₂ H ₄ ) _n OR ₂ (I) (wherein R ₁ and R ₂ may be the same or different,
And (b) an alkyl (meth) acrylate, each of which represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and n represents an integer of 1 to 23). Ester (alkyl group has 1 to 10 carbon atoms) 19.9 to 99.8% by weight; (c) Unsaturated monomer having two or more radically polymerizable polymerizable groups having different reactivity in the molecule 0.01 to 10% by weight; and (d) 0 to 40 ethylenically unsaturated monomer (excluding ethylenically unsaturated carboxylic acid) copolymerizable with the above (a), (b) and (C). % By weight (however, (a) + (b) +
(C) + (d) = 100% by weight] to produce a polymer, and the polymer is photocrosslinked. 8. The method according to claim 7, wherein the light used in the photocrosslinking step is visible light of 360 nm to 550 nm, and a photosensitizer is used.