JPH08325545A - Tacky base - Google Patents

Abstract

PURPOSE: To obtain a tacky base containing a cross-linked polymer prepared by polymerizing a specific monomer, excellent in tack to skin, useful as a patch, a pad for medical treatment, a skin preparation for external use, etc. CONSTITUTION: This tacky base comprises a polymer obtained by polymerizing (A) a (meth)acrylic acid glycosyloxyalkyl ester with (B) a (meth)acrylic acid hydroxyalkyl ester, (C) a (meth)acrylic acid alkyl ester and (D) a polyfunctional monomer in the molar ratio of the component A/the component B/the component C of (0.1-10):(10-40):(5-20) and in the molar ratio of the component D to the total of the component A to the component C of 1:(100-3200). The tacky agent, for example, can be obtained by polymerizing 2-glycosyloxyethyl (meth)acrylate with 2-hydroxyethyl (meth)acrylate, n-butyl (meth)acrylate and ethylene glycol di(meth)acrylate.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention contains a cross-linked polymer obtained by polymerizing a specific monomer and exhibits excellent adhesiveness to the skin, and is useful as a patch, a medical pad, an external preparation for skin and the like. A sticky base.

[0002]

2. Description of the Related Art Heretofore, as a pressure-sensitive adhesive to be used by sticking to the skin, there has been known one in which a hydrophilic pressure-sensitive adhesive gel is adhered to a ready-made support (Japanese Patent Laid-Open No. 62-111918, Japanese Patent Laid-Open No. 111918/1987). JP-A-63-225314, JP-A-63-246323.
No.). Examples of the support used here include plastic sheets such as polyethylene, polypropylene, ethylene-vinyl acetate copolymer, vinylon, polyester, polyurethane and nylon; non-woven fabrics such as rayon and polyester; polyester, acrylic, silk and cotton. Woven cloth and the like can be mentioned. However, among these supports, the plastic sheet is peeled off because of poor adhesion with the gel, and the non-woven fabric and woven fabric are poor in flexibility,
Moreover, there were problems such as insufficient astringency.

As the pressure-sensitive adhesive impregnated with a water-soluble drug, a water-soluble polymer or a water-soluble polymer having a cross-linked gel structure is used. For example, polyacrylic acid, polyacrylic acid salt, polyvinyl Alcohol, polyvinylpyrrolidone, carboxymethylcellulose sodium salt,
Gelatin, starch, etc. are used. Among these, polyacrylic acid and polyacrylic acid salts are used in which a gel body obtained by crosslinking these with a polyvalent metal salt is impregnated with a drug (JP-A-53-15413). However, this cross-linked gel has a problem that it becomes a non-uniform gel because the cross-linking reaction is fast.

In order to solve such a problem, attempts have been made to delay the reaction rate by using a polyvalent metal salt which is poorly soluble in water (Japanese Patent Laid-Open No. 57-42617), but the reaction is remarkably slow. If the amount of the polyvalent metal salt is increased in order to accelerate the reaction rate, the swelling property of the gel is lowered and the drug absorbability is also lowered.

Therefore, in order to increase the crosslinking reaction rate of the poorly water-soluble polyvalent metal salt, ethylenediaminetetraacetic acid (EDT
A), an attempt was made to add a sequestering agent such as citric acid and lactic acid (JP-A-54-106598, JP-A-59-11614, JP-A-59-110617, etc.) There was a problem that the sequestration of the metal ions was not sufficient, the crosslinking reaction rate did not remarkably increase, and the swelling property of the gel was also reduced by the unsealed polyvalent metal ions.

As an adhesive in which a poorly water-soluble drug such as indomethacin is impregnated, an acrylic adhesive impregnated with indomethacin and a percutaneous absorption enhancer is known (Japanese Patent Publication No. 58-43368). , Japanese Patent Sho 59-76
No. 88), the solubility of the drug in the adhesive was small, and a clinically necessary amount could not be incorporated. Therefore, a monomer having an acid amide bond in the molecule and (meth)
Using a copolymer of acrylic acid ester (Japanese Patent Laid-Open No. 58-138426) or a method of co-pulverizing a water-soluble polymer and a poorly water-soluble drug and mixing with a carboxyvinyl polymer, a basic substance and water (special Kaihei 3-135924) and the like have also been attempted, but none of them were sufficiently satisfactory in terms of drug solubility, crosslinking reaction rate, control of swelling degree, and the like.

[0007]

Therefore, an object of the present invention is to provide an adhesive base having good swelling property, capable of uniformly swelling, and exhibiting excellent adhesiveness to the skin. To do.

[0008]

Under such circumstances, as a result of intensive studies by the present inventors, when a polymer obtained by polymerizing four specific types of monomers is used, excellent adhesiveness to skin is obtained. The present invention has been completed by finding that an adhesive base having good swelling property can be obtained.

That is, the present invention contains a polymer obtained by polymerizing a (meth) acrylic acid glucosyloxyalkyl ester, a (meth) acrylic acid hydroxyalkyl ester, a (meth) acrylic acid alkyl ester and a polyfunctional monomer. An adhesive base is provided.

The present invention also provides a skin external preparation containing the adhesive base and the drug.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The polymer used in the present invention is
(Meth) acrylic acid glucosyloxyalkyl ester (a), (meth) acrylic acid hydroxyalkyl ester (b), (meth) acrylic acid alkyl ester (c)
And a polyfunctional monomer (d) are polymerized. As the (meth) acrylic acid glucosyloxyalkyl ester (a) used here, for example, the following general formula (1) is used.

[0012]

Embedded image

(In the formula, R represents a hydrogen atom or a methyl group, G-O- represents a sugar residue having no protecting group, and n represents 2
Or 3) is included.

In the general formula (1), the sugar residue represented by G-O- is preferably one derived from a monosaccharide or oligosaccharide having 1 to 10, particularly 1 to 5 sugar units. Here, specific examples of the monosaccharide include hexoses such as glucose, mannose, galactose, glucosamine, mannosamine, and galactosamine, and pentoses such as arabinose, xylose, and ribose. Further, specific examples of oligosaccharides include maltose, lactose, trehalose, cellipose, isomaltose, gentiobiose, melibiose, laminaribiose, chitobiose, xylobiose, mannobiose, sophorose and other disaccharides, maltotriose, isomalttriose, Maltotetraose, maltopentaose, mannotriose, manninotriose, etc., and hydrolysates of starch, cellulose, chitin, chitosan, mannan (eg, pharmacopoeial dextrin, acrodextrin, British gum, cellodextrin, etc.), etc. Is mentioned.

It is preferable that R is a methyl group and n is 2. Particularly preferred monomers (a) include 2-glucosyloxyethyl methacrylate, 2-mannosyloxyethyl methacrylate and 2-galactosyloxyethyl methacrylate.

Examples of the (meth) acrylic acid hydroxyalkyl ester (b) include (meth) acrylic acid 2-hydroxyethyl (2-hydroxyethyl (meth) acrylate) and (meth) acrylic acid hydroxypropyl. To be Of these, 2-hydroxyethyl methacrylate is particularly preferable from the viewpoint of safety for living bodies.

Examples of the alkyl (meth) acrylate (c) include ethyl (meth) acrylate,
N-Butyl (meth) acrylate, isobutyl (meth) acrylate, hexyl (meth) acrylate, octyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, isooctyl (meth) acrylate, (meth) acrylic Decyl acid, isodecyl (meth) acrylate, (meth)
Examples thereof include lauryl acrylate and stearyl (meth) acrylate. Among these, n-butyl acrylate (n-butyl acrylate) and 2-ethylhexyl acrylate, which have been widely used as the adhesive layer component of poultices, are particularly preferable.

The mixing ratio of these (meth) acrylic acid glucosyloxyalkyl ester (a), (meth) acrylic acid hydroxyalkyl ester (b) and (meth) acrylic acid alkyl ester (c) is 0. 1 to
It is preferably 10:10 to 40: 5 to 20, particularly 0.1 to 10:19:10, and further 0.1 to 2: 19: 1.
0 is preferred.

The polyfunctional monomer (d) may be any as long as it has two or more functional groups in one molecule, and examples thereof include ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate and triethylene. Glycol di (meth) acrylate, polyethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate, polypropylene glycol di (meth) acrylate, 1,4-butylene glycol di (meth) acrylate, 1,6-hexanediol di Those having two or more vinyl groups in one molecule such as (meth) acrylate and 1,10-decanediol di (meth) acrylate; diallyl phthalate, diallyl malate, diallyl adipate, triallyl isocyanate, diethylene group Those having two or more allyl groups in one molecule, such as a call bisallylcarbonate; N,
N'-methylene bis acrylamide etc. are mentioned. Of these, particularly highly safe ethylene glycol dimethacrylate (EGDMA) and triethylene glycol dimethacrylate (TEGDMA) are preferable.

Of these polyfunctional monomers (d) with (meth) acrylic acid glucosyloxyalkyl ester (a), (meth) acrylic acid hydroxyalkyl ester (b) and (meth) acrylic acid alkyl ester (c) The molar ratio to the total amount is preferably 1: 100 to 3200, and particularly preferably 1: 200 to 800.
The smaller the molar ratio of the polyfunctional monomer is, the higher the swelling rate is, but on the other hand, the mechanical strength is lowered. Therefore, the molar ratio is preferably within the above range.

Further, the polymer used in the present invention may be polymerized with a monomer other than the monomers (a) to (d). Examples of such other monomers include those having a carboxyl group, those having an amide group, those having an amino group, and the like. Examples of the monomer having a carboxyl group include unsaturated carboxylic acids such as (meth) acrylic acid, maleic acid, fumaric acid, crotonic acid, etc .;
For example, (meth) acrylamide, dimethyl (meth) acrylamide, diethyl (meth) acrylamide, butoxymethyl (meth) acrylamide, ethoxyethyl (meth) acrylamide, diacetone (meth) acrylamide, vinylpyrrolidone, and the like; a monomer having an amino group Examples thereof include dimethylamino (meth) acrylate, diethylamino (meth) acrylate and the like; further, vinyl acetate, styrene, vinyl chloride,
Acrylonitrile, ethylene, propylene, butadiene, etc. can be mentioned.

Polymerization of (meth) acrylic acid glucosyloxyalkyl ester (a), (meth) acrylic acid hydroxyalkyl ester (b), (meth) acrylic acid alkyl ester (c) and polyfunctional monomer (d) is It may be carried out according to a usual method, and the polymerization method is not particularly limited.

The polymerization initiator used in the case of radical polymerization is not particularly limited and can be appropriately selected depending on the monomer, reaction solvent and the like. For example, when water or a solvent containing water is used as a reaction solvent, a persulfate such as ammonium persulfate or potassium persulfate is used, and an organic solvent is used as the hydrophobic monomer or reaction solvent. In the case, peroxides such as benzoyl peroxide, di-tert-butyl peroxide, acetyl peroxide; 2,2'-azobisisobutyronitrile, 2,
2'-azobis (2-methylbutyronitrile), 2,
Examples thereof include azo compounds such as 2'-azobis- (2,4-dimethylvaleronitrile) and dimethyl-2,2'-azobis (2-methylpropionate). The polymerization initiator is 0.01 to 10% by weight based on the total amount of monomers.
It is preferred to add.

Examples of the solvent used when carrying out the polymerization by solution polymerization include water, methanol, isopropyl alcohol, dioxane, tetrahydrofuran, acetone, acetonitrile, dimethylformamide, dimethylsulfoxide, etc. These may be used alone or in combination of two kinds. The above combinations can be used.

The polymerization reaction is preferably carried out at 25 to 100 ° C. for 2 to 72 hours, for example, when an ordinary radical polymerization initiator is used. In particular, in order to decompose the polymerization initiator and increase the degree of polymerization, it is preferable to carry out the reaction for a certain period of time and then further raise the temperature for polymerization.

Further, without using a polymerization initiator, radiation,
It is also possible to irradiate the monomer with light, ultraviolet rays, low-temperature plasma or the like to generate a polymerization active species and then perform polymerization. Here, as radiation, α rays, β rays, γ rays, accelerated electrons,
High-energy ionizing radiation such as X-rays can be used, and of these, γ-rays and accelerated electrons are preferably used. For light and ultraviolet rays, a mercury lamp is generally used, and a filter is preferably used, and a wavelength of 300 nm or more is preferably used. The low temperature plasma is preferably glow discharge or corona discharge. These reactions are preferably performed by adding an oxygen scavenger. By not using the polymerization initiator, the toxicity of the polymerization initiator can be eliminated. Further, the polymer obtained after the polymerization reaction can be purified according to a usual method.

Among the polymers obtained by carrying out the polymerization reaction as described above, 2-glucosyloxyethyl (meth) is particularly preferable.
Those obtained by polymerizing acrylate, 2-hydroxyethyl (meth) acrylate, n-butyl (meth) acrylate and ethylene glycol di (meth) acrylate are preferable.

The polymer thus obtained can be swollen as it is or by pulverizing it and impregnating it with a solvent. As the solvent used here,
Water; polyhydric alcohols such as ethylene glycol, propylene glycol, diethylene glycol, glycerin, polyethylene glycol, triethylene glycol, ethylene glycol, monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, polypropylene glycol, batyl alcohol, pentaerythritol, sorbitol Ethanol, isopropyl alcohol, lauryl alcohol,
Examples thereof include monohydric alcohols such as cetanol, stearyl alcohol, oleyl alcohol, and lanolin alcohol, and it is preferable to use one type or a combination of two or more types. Among these solvents, an alcohol-water mixed solvent, particularly a polyhydric alcohol-monohydric alcohol-water mixed solvent, is preferable, the polyhydric alcohol is polyethylene glycol, and the monohydric alcohol is isopropyl alcohol. When polyhydric alcohol, monohydric alcohol and water are mixed and used, the mixing ratio is
Polyhydric alcohol: Monohydric alcohol: Water = 0.5-5:
It is preferably 0.1 to 2: 1.

The polymer can be used as it is or in the form of a plate, but if it is used by finely pulverizing it, the adhesive force can be further increased. By pulverizing, the solvent can be uniformly impregnated in the polymer,
Further, the surface area per unit weight can be increased, and the swelling rate and the swelling degree can be increased. It is known that the swelling time of the gel is proportional to the square of the length of the gel, and it is preferable to make the particle size of the gel as small as possible in order to increase the swelling property in a short time. In the present invention, The finely pulverized polymer preferably has a particle size of 200 to 50 mesh.

When used as an adhesive base, the plate polymer is swollen in an alcohol-water mixed solvent and cut into an arbitrary area, and the fine powder polymer is mixed with the alcohol-water mixed solvent in a ratio of 1: 1. -10, preferably 1: 3 to 7 (weight ratio), and then spread over any area between surface-inert resin or rubber such as silicone or Teflon containing spacers of any thickness. It can be produced by

Further, the polymer used in the present invention has a swelling ratio of 300% or more when impregnated with a solvent,
The adhesiveness to the skin is further enhanced, which is preferable. In order to increase the swelling rate, the crosslinking density may be lowered, or a crosslinking agent having a long chain length may be used, and the crosslinking agent may be appropriately selected within a range not impairing the mechanical strength. The swelling ratio is preferably set appropriately according to the application of the adhesive base of the present invention.

The swelling ratio can be calculated by the following equation.

[0033]

[Equation 1]

Further, the polymer swollen by impregnating with a solvent preferably has a peel strength against glass of 80 g / cm ² or more, and particularly when it is 100 g / cm ² or more, excellent adhesion to the skin is obtained. It is preferable because it can be obtained.

The peel strength can be calculated by the following equation.

[0036]

[Equation 2]

The adhesive base of the present invention can be used by adhering it to a ready-made support. Examples of the support used here include polyethylene, polypropylene,
Examples thereof include ethylene-vinyl acetate copolymer, plastic sheets such as vinylon, polyester, polyurethane and nylon, non-woven fabrics such as rayon and polyester, and woven fabrics such as polyester, acrylic, silk and cotton.

The adhesive base of the present invention can be applied as a skin external preparation by dissolving various drugs and the like in a solvent and impregnating the solution with a polymer, and the transdermal absorbability of the drug is also good. Can be The drug used here is not particularly limited as long as it is a drug that can be absorbed transdermally, and examples thereof include antipyretic and anti-inflammatory analgesics, steroidal anti-inflammatory agents, vasodilators, antihypertensive / arrhythmic agents, antihypertensive agents, antitussive expectorants. Agents, antitumor agents, local anesthetics, hormone agents, antiasthma / allergic agents, antihistamines, anticoagulants, antispasmodics,
Cerebral circulation and metabolism improver, antidepressant / anxiolytic, vitamin D
Agents, hypoglycemic agents, anti-ulcer agents, hypnotics, antibiotics and the like.

Examples of the antipyretic and antiphlogistic analgesic include indomethacin, salicylic acid, aspirin, acetaminophen, diclofenac sodium, ibuprofen, sulindac, naproxen, ketoprofen, flufenamic acid, ibufenac, fenbufen, alclofenac, phenylbutazone, mefenamic acid, Examples include bendazac, piroxicam, flurbiprofen, pentazocine, buprenophine hydrochloride, butorphanol tartrate and the like.

Examples of the steroidal anti-inflammatory agent include hydrocortisone, prednisolone, fluocinolone acetonide, fludroxycortide, methylprednisolone, hydrocortisone acetate, triamcinolone acetonide, dexamethasone, betamethasone acetate, diflucortron valerate, and propionate. Examples include clobetasol and fluocinonide.

Examples of vasodilators include diltiazem, verapamil, pentaerythritol tetranitrate, dipyridamole, isosorbide dinitrate, nifedipine and the like.

Examples of the antihypertensive / arrhythmic agent include proparanolol, atenolol, pindolol, quinidine sulfate, azimarin, alprenolol hydrochloride, metoprolol tartrate, nadolol, timolol maleate, disopyramide and the like.

Examples of the antihypertensive agent include clonidine hydrochloride, captopril, prazosin hydrochloride, penbutol sulfate sulfate, guanabenz acetate, guanfacine hydrochloride, bunazosin hydrochloride, enalapril maleate, arotinolol hydrochloride, benitrolol hydrochloride and the like.

Examples of the antitussive expectorant include procaterol hydrochloride, terbutaline sulfate, fenoterol hydrobromide, tulobuterol hydrochloride, ambroxol hydrochloride, pirbuterol hydrochloride, mabuterol hydrochloride, clenbuterol hydrochloride, trimetoquinol hydrochloride and formoterol fumarate. Can be mentioned.

Examples of the antitumor agent include glycopyrronium bromide and the like.

Examples of the local anesthetic include benzocaine, procaine, lidocaine and tetracaine.

Examples of the hormonal agents include steroid hormones such as estrogen, estradiol, testosterone, progesterone and prostaglandins, and peptide hormones such as insulin.

Examples of the anti-asthma / allergic agent include ketotifen fumarate, azelastine hydrochloride, sodium cromoglycate and the like.

Examples of the antihistamine include cycloheptazine hydrochloride, diphenhydramine hydrochloride, phenbenzamine, mequitazine and the like.

Examples of the anticoagulant include heparin, urokinase, tPA and the like. Examples of the antispasmodic include scopolamine, clofluperol and the like.

Examples of the agents for improving cerebral circulation and metabolism include vinpocetine, flunarizine hydrochloride, nicardipine hydrochloride, brovincamin fumarate, dihydroergotoxine mesylate, ifenprodil tartrate, isoxuprine hydrochloride and the like.

Examples of the antidepressant / anxiolytic agents include maprotiline hydrochloride, etizolam, diazepam, promazepam,
Amitriptyline hydrochloride, mianserin hydrochloride and the like can be mentioned. Examples of the vitamin D agent include alfacalcidol, ergocalciferol and the like.

Examples of the hypoglycemic agent include glibenclamide, gliclazide and the like. Examples of the anti-ulcer agent include clevoprid malate, famotidine, glycopyrronium bromide and the like.

Examples of the sleeping agent include phenobarbital, amobarbital and the like. Examples of antibiotics include tetracycline and chloramphenicol.

The blending amount of these drugs varies depending on the clinically required amount, the dose per administration, etc., but is preferably 0.1 to 10% by weight with respect to the alcohol-water mixed solvent. In addition, if necessary, components such as a skin stimulant, a percutaneous absorption enhancer, a stabilizer, an antiaging agent, an ultraviolet absorber, an antioxidant, etc., which are used in ordinary skin external preparations, may be added. The pH can be adjusted by the acid and alkali.

When the drug is mixed, it can be used as a pad for iontophoresis, phonophoresis, etc., in addition to the usual patch.

[0057]

EFFECTS OF THE INVENTION The adhesive base of the present invention has good swelling property, can swell uniformly, and exhibits excellent adhesiveness to the skin. Therefore, the adhesive layer of the patch and various medical pads It is also useful as an external preparation for skin impregnated with a drug. In particular, in the case of a skin external preparation containing a drug, transdermal absorbability of the drug is also good.

[0058]

EXAMPLES Next, the present invention will be further described with reference to examples, but the present invention is not limited to these examples.

Example 1 2-Glucosyloxyethyl methacrylate (hereinafter referred to as
GEMA: H of 2-hydroxyethyl methacrylate (hereinafter referred to as “HEMA”) and n-butyl acrylate (hereinafter referred to as “BA”)
Ethylene glycol dimethacrylate (hereinafter referred to as “EGDMA”) was added at a ratio of 800: 1 (molar ratio) to the mixed monomer of EMA: BA = 0.1 to 10:19:10 (molar ratio). 0.1% by weight of 2,2'-azobisisobutyronitrile was added to the total amount of this monomer, and after nitrogen substitution and deaeration, polymerization reaction was carried out at 65 ° C for 5 hours and further at 75 ° C for 1 hour. I went. After the completion of the polymerization reaction, the procedure of (swelling with isopropyl alcohol-washing with water-vacuum drying-pulverization) was repeated twice for purification. The purified polymer was pulverized with a pulverizer and passed through a 80 mesh sieve to obtain a fine powder polymer. Fine powder polymer and polyethylene glycol-isopropyl alcohol-water (2:
1: 1) The mixed solution is mixed in a weight ratio of 1: 5, and 0.4 g of the mixed solution is spread on a 2 × 2 cm area between silicone sheets containing a spacer having a thickness of 0.5 mm to form a pad. It was made.

Example 2 Between slide glasses containing 0.5 mm spacers,
A polymerization reaction was carried out in the same manner as in Example 1. After completion of the polymerization reaction,
The procedure of (swelling with isopropyl alcohol-washing with water-drying) was repeated twice for purification to obtain a plate-like polymer.

Example 3 GEMA: HEMA: BA = 1: 19: 10 (molar ratio)
EGDMA was added to the mixed monomer of 1: 1 to 1600: 1 (molar ratio) to obtain a fine powder polymer in the same manner as in Example 1, and further a pad was prepared.

Example 4 Between slide glasses containing 0.5 mm spacers,
A polymerization reaction was carried out in the same manner as in Example 3. After completion of the polymerization reaction,
Purification was carried out in the same manner as in Example 2 to obtain a plate polymer.

Example 5 GEMA: HEMA: BA = 1: 19: 10 (molar ratio)
800: 1 (molar ratio) to the mixed monomer of EGD
MA or triethylene glycol dimethacrylate (T
EGDMA) was added, a fine powder polymer was obtained in the same manner as in Example 1, and a pad was prepared.

Example 6 Between slide glasses containing 0.5 mm spacers,
A polymerization reaction was carried out in the same manner as in Example 5. After completion of the polymerization reaction,
Purification was carried out in the same manner as in Example 2 to obtain a plate polymer.

Test Example 1 Among the polymers obtained in Examples 1 to 6, a plate-like polymer was cut into 1 × 1 cm and dried in vacuum to obtain indomethacin 1
It was swollen by immersing it in a mixed solution of 49 parts by weight of PEG400, 25 parts by weight of isopropyl alcohol and 25 parts by weight of water. Further, 1 part by weight of the polymer obtained by pulverizing the plate-shaped polymer with a pulverizer and passing through a 80-mesh sieve or the fine powder polymer obtained in the example was mixed with the same mixed solution 5
It was mixed with a part by weight, spread, and swollen. When the state after swelling was visually observed, the solvent was uniformly impregnated in all cases. Further, among the plate polymer and the fine powder polymer, the fine powder polymer was more uniform.

Test Example 2 The plate-like polymer obtained in the example was cut into 1 × 1 cm, vacuum dried, and immersed in PEG400 and PEG400 aqueous solution. Measure the weight at the time of saturated swelling before and after one week,
The swelling ratio was calculated according to the formula (1).

FIG. 1 shows a comparison of the swelling ratios of the plate-like polymers obtained by changing the mixing ratio of GEMA obtained in Example 2.
The swelling ratio became maximum when the water content was 20%.

A comparison of the swelling ratios of the plate-like polymers obtained by changing the crosslinking density of the crosslinking agent EGDMA obtained in Example 4 is shown in FIG. It was confirmed that the lower the crosslink density, the higher the swelling rate, especially when the water content is low.

A comparison of the swelling ratios of the plate-like polymers having different lengths of the cross-linking agent obtained in Example 6 is shown in FIG. The swelling ratio was higher when TEGDMA, which had a longer chain length, had a lower water content.

Test Example 3 A pad made of the plate-like polymer or fine powder polymer obtained in the example was saturated and swollen in a mixed solvent of 50 parts by weight of PEG400, 25 parts by weight of isopropyl alcohol and 25 parts by weight of water. After that, it was cut into 1 × 1 cm, and the peeling load when peeling at a constant speed of 2 cm / min with the device configuration shown in FIG. 4 was measured, and the peel strength was calculated from the above formula (2).

FIG. 5 shows the peel strength of the fine powder polymer pad and the plate-like polymer in which the mixing ratio of GEMA was varied. The adhesive strength of the pad was stronger irrespective of the blending amount of GEMA, and the maximum was shown at the GEMA blending amount of 3.3 mol% (mixing molar ratio; GEMA: HEMA: BA = 1: 19: 10).

FIG. 6 shows the peel strength of the fine powder polymer pad and the plate-like polymer having different crosslink densities of EGDMA. The lower the crosslink density, the higher the peel strength, and there was almost no change when the blending amount of EGDMA was 0.125 mol% (crosslink density 800: 1) or less. Moreover, the pad showed higher adhesive strength.

FIG. 7 shows the peel strength of the pad prepared from the fine powder polymer having different lengths of the cross-linking agent obtained in Example 5.
It was shown to. The use of TEGDM had stronger adhesive strength and higher swelling rate.

Example 7 A skin external preparation (pad) containing indomethacin was produced, and the blood concentration of indomethacin when it was applied was measured. (1) Production of pad: An indomethacin solution having the composition shown in Table 1 was prepared.

[0075]

Table 1 Indomethacin 1.2 (wt%) Polyethylene glycol 400 50.0 Isopropyl alcohol 24.4 Purified water 24.4

Next, GEMA: HEMA: BA = 1: 1.
EGDMA for a mixed monomer of 9:10 (molar ratio)
Was added at a ratio of 800: 1 (molar ratio), and a fine powder polymer was obtained in the same manner as in Example 1. After mixing 1 part by weight of the finely divided polymer and 5 parts by weight of the indomethacin solution, 0.5
4.9 between silicone sheets with mm spacers
g was taken and spread to 7 cm × 7 cm to obtain a pad.

(2) Test method: The abdominal skin of a JW rabbit (average weight 2.5 kg, male) was hair-removed, and then a pad was attached to the center. At 2, 4, and 6 hours after application, 1 ml of blood was collected from the heart, and the concentration of indomethacin contained in plasma was measured by the HPLC method.

(3) Results: The time course of blood concentration of indomethacin is shown in FIG. From this result, it was confirmed that after 2 hours or more, indomethacin was absorbed and the absorbability was good.

[Brief description of drawings]

FIG. 1 is a diagram showing a comparison of a swelling ratio depending on a mixing ratio of GEMA.

FIG. 2 is a diagram showing a comparison of swelling rates according to crosslink densities.

FIG. 3 is a diagram showing a comparison of swelling ratios depending on chain lengths of crosslinking agents.

FIG. 4 is a diagram showing an apparatus configuration for measuring peel strength in Test Example 3.

FIG. 5 is a diagram showing a comparison of peel strength depending on a mixing ratio of GEMA.

FIG. 6 is a diagram showing a comparison of peel strength according to crosslink density.

FIG. 7 is a diagram showing a comparison of peel strength depending on the chain length of a crosslinking agent.

FIG. 8 is a graph showing a time course of blood concentration of indomethacin in Example 7.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 45/00 AAE A61K 45/00 AAE AAG AAG AAM AAH AAK AAK AAM AAM AAQ AAQ AA BAY AA ABP ABR ABR ABU ABU ACB ACB ACF ACF ACG ACG ACH ACH ACL ACL ADF ADF ADP ADP ADU ADU AEE AEE AEE AEE AEE AEM AEM A61L 15/58 C0J13 C08J8C8JC8F8C8F20 / 28C0F8C8F20C28F8 06

Claims (13)

[Claims] 1. An adhesive base containing a polymer obtained by polymerizing a (meth) acrylic acid glucosyloxyalkyl ester, a (meth) acrylic acid hydroxyalkyl ester, a (meth) acrylic acid alkyl ester and a polyfunctional monomer. . 2. The molar ratio of (meth) acrylic acid glucosyloxyalkyl ester, (meth) acrylic acid hydroxyalkyl ester and (meth) acrylic acid alkyl ester is from 0.1 to 10:10 to 40: 5 to 20. The adhesive base according to claim 1. 3. The molar ratio of the polyfunctional monomer to the total amount of (meth) acrylic acid glucosyloxyalkyl ester, (meth) acrylic acid hydroxyalkyl ester and (meth) acrylic acid alkyl ester is 1: 100 to.
The adhesive base according to claim 1, which is 3200. 4. An adhesive containing a polymer obtained by polymerizing 2-glucosyloxyethyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, n-butyl (meth) acrylate and ethylene glycol di (meth) acrylate. Nature base. 5. The adhesive base material according to claim 1, wherein the polymer is impregnated with a mixed solvent of alcohol and water. 6. The polymer is impregnated in a mixed solvent of polyhydric alcohol-monohydric alcohol-water.
The adhesive base described. 7. The adhesive base according to claim 6, wherein the weight ratio of polyhydric alcohol-monohydric alcohol-water is 0.5 to 5: 0.1 to 2: 1. 8. The adhesive base according to claim 5, wherein the polymer is finely pulverized. 9. The adhesive base according to claim 8, wherein the weight ratio of the polymer to the mixed solvent of alcohol and water is 1: 1 to 10. 10. The adhesive base according to claim 5, wherein the polymer swollen by impregnating with a solvent has a swelling ratio of 300% or more. 11. The adhesive base according to claim 10, wherein the peel strength of the polymer with respect to glass is 80 g / cm ² or more. 12. A skin external preparation containing the adhesive base according to any one of claims 1 to 11 and a drug. 13. The drug is an antipyretic anti-inflammatory drug, a steroidal anti-inflammatory drug, a vasodilator, an antihypertensive / arrhythmic drug, an antihypertensive drug, an antitussive expectorant, an antitumor drug, a local anesthetic, a hormone drug, and an antiasthma.・ Allergic agents, antihistamines, anticoagulants, antispasmodics, cerebral circulation / metabolic agents, antidepressants / anxiety agents,
The external preparation for skin according to claim 12, which is a vitamin D agent, a hypoglycemic agent, an anti-ulcer agent, a sleeping agent or an antibiotic.