JPH11164878A - New medical polymer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a gel type self-adhesive agent for plaster which has sufficient self-adhesive force to stick to the skin as well as sufficient releasing easiness so as not to damage the skin when released, and is less remained. SOLUTION: This gel type self-adhesive agent is composed of a polymer containing acid group (A) containing 1 to 40 wt.% of an ethylenic unsaturated monomer containing carboxyl group, and a polymer containing basicity group (B) containing 20 to 90 wt.% of monomer which is represented by CH2=C(R1) COO(CH2CH(R2)O)nR3 (where, R1, R2 represent hydrogen or methyl group, n represents integer between 2 and 10, R3 represents alkyl group having 6 to 24 carbon), and liquid component (C) compatible with both polymers, and the ratio of total containing amount of (A) and (B) to that of (C) is 1.0:0.25 to 1.0:2.0.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel pressure-sensitive adhesive and a patch. More specifically, the present invention relates to a medical pressure-sensitive adhesive which can be used for protection of the skin surface and the like, and a patch which is stuck to the skin surface and transdermally absorbs the drug.

[0002]

2. Description of the Related Art In recent years, various transdermal absorption tapes for administering a drug into a living body through a skin surface have been developed.
Usually, it is desired that such a tape agent has not only adhesive strength required to prevent detachment from the skin-adhering surface, but also easy peeling to such an extent that the skin surface (stratum corneum) is not damaged when peeled after use. ing. 2. Description of the Related Art Conventionally, a method of preventing a stratum corneum from being damaged at the time of peeling by adding a liquid component such as liquid paraffin to a rubber-based adhesive has been performed. However, in the case of these adhesives, antioxidants,
It is essential to add low molecular components such as a stabilizer and a tackifier resin, and it is difficult to completely suppress skin irritation even if the exfoliation of the stratum corneum can be suppressed. In addition, JP 60
JP-A-208912 discloses a method for improving the stability of an adhesive by using a polyester elastomer instead of a natural rubber or a synthetic rubber. In this method, the addition of an antioxidant or a stabilizer can be eliminated, but the addition of a low molecular weight (number average molecular weight <2000) tackifier resin is essential,
Therefore, skin irritation due to them cannot be avoided. Further, JP-A-3-220120 discloses an acrylic gel pressure-sensitive adhesive comprising a crosslinked gel layer containing an acrylate polymer and a liquid component compatible with the polymer, formed on at least one surface of a support. Has been proposed. According to the proposal, the gel-like pressure-sensitive adhesive can contain a large amount of a liquid component, so that the adhesive force and the ease of peeling can be balanced as compared with the conventional non-crosslinked pressure-sensitive adhesive, and the peeling of the stratum corneum is also reduced. . However, in the above-mentioned proposed gel adhesive, in order to increase the cohesive strength of the adhesive, the acrylic acid unit contained in the acrylate-based polymer is converted to a polyvalent metal alcoholate such as Al ³⁺ or titanium or trifunctional. It is necessary to crosslink by a chemical reaction using a low molecular crosslinking agent such as isocyanate. Generally, it is difficult to achieve a reaction rate of 100% in a polymer reaction, and usually, unreacted reagent remains in the system. Therefore, in a gel pressure-sensitive adhesive obtained by chemically reacting such a cross-linking agent, the cross-linking catalyst and the cross-linking agent may remain in the pressure-sensitive adhesive, causing skin irritation and rash. In addition, a method using a polymer that forms a polyion complex can be considered instead of crosslinking by a chemical reaction using a low-molecular crosslinking agent. The dope gelled before casting the adhesive, and it was difficult to obtain a homogeneous adhesive.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to have an adhesive force necessary to prevent detachment from a skin-adhering surface and to have a peeling property that does not damage the skin surface when peeling after use. Another object of the present invention is to provide a gel-type pressure-sensitive adhesive for patches, which has a small amount of adhesive residue.

[0004] It is a further object of the present invention to provide a patch which can be used for protecting the skin, etc., using such a gel-type adhesive, or a drug containing a drug in such an adhesive, which can be effectively transdermally absorbed. An object of the present invention is to provide a patch that can be made to adhere.

The inventors of the present invention have made intensive studies to achieve such an object, and as a result, have been found that instead of the above-described chemical reaction crosslinking using a low-molecular crosslinking agent, a simple compound having a specific amphiphilic side chain is used. It has been found that by mixing a polymer comprising a monomer having a monomer and an acidic group with a polymer having a basic group and a liquid component, a gel-like pressure-sensitive adhesive free of seepage of the liquid component can be obtained. It was completed.

[0006]

That is, the present invention comprises 1 to 40% by weight of a carboxyl group-containing ethylenically unsaturated monomer and 20 to 90% by weight of a monomer represented by the following general formula (1). (A), a basic group-containing polymer (B), and a liquid component (C) compatible with both polymers, and the total content of (A) and (B) and (C) And a patch comprising the gel-like pressure-sensitive adhesive and a support having a weight ratio of 1.0: 0.25 to 1.0: 2.0. CH2 = C (R1) COO (CH2CH (R2) O) nR3 Formula (1) (where R1 and R2 are hydrogen or methyl groups, and n is 2 or more and 1
An integer of 0 or less, R3 represents an alkyl group having 6 to 24 carbon atoms. )

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION As the acidic group-containing polymer (A) used in the present invention, the monomer is a carboxyl group-containing ethylenically unsaturated monomer in an amount of 1% by weight to 40% by weight and the following formula (1) ) Is a polymer containing 20% by weight or more and 90% by weight or less of the monomer represented by the formula (1). CH2 = C (R1) COO (CH2CH (R2) O) nR3 Formula (1) (where R1 and R2 are hydrogen or methyl groups, and n is 2 or more and 1
An integer of 0 or less, R3 represents an alkyl group having 6 to 24 carbon atoms. When the content of the carboxyl group-containing ethylenically unsaturated monomer is less than 1%, or when the content of the monomer of the above formula (1) exceeds 90% by weight, the cohesive force of the adhesive decreases, and When applied to the skin, the pressure-sensitive adhesive remains on the skin surface, that is, adhesive residue is apt to occur, which is not preferable. When the amount of the monomer represented by the formula (1) is less than 20% by weight, the polymer becomes difficult to dissolve in a low-boiling-point polar solvent such as alcohol or an alcohol mixed solvent, and is mixed with a polymer solution containing a basic group. In addition, the adhesive dope gels, and it becomes difficult to coat the adhesive, which is not preferable. On the other hand, when the amount of the carboxyl group-containing ethylenically unsaturated monomer exceeds 40% by weight, the adhesive strength required for skin adhesion cannot be obtained, which is not preferable.

Specific examples of the monomer of the above formula (1) include diethylene glycol octyl ether (meth) acrylate, tetraethylene glycol octyl ether (meth) acrylate, tetraethylene glycol dodecyl ether (meth) acrylate, hexaethylene Glycol octadecyl ether (meth) acrylate,
Heptaethylene glycol octadecyl ether (meth) acrylate, octaethylene glycol hexadecyl ether (meth) acrylate, decaethylene glycol hexadecyl ether (meth) acrylate, pentapropylene glycol dodecyl ether (meth) acrylate, pentapropylene glycol octadecyl ether (meth) Acrylate, heptaethylene glycol tripropylene glycol octadecyl ether (meth) acrylate, and the like. Specific examples of the carboxyl group-containing ethylenically unsaturated monomer include acrylic acid, methacrylic acid, itaconic acid, and maleic acid. Among these, acrylic acid is particularly preferred from the viewpoint of cohesive strength, adhesive strength, and polymerizability.

In the present invention, a monomer other than the carboxyl group-containing ethylenically unsaturated monomer of the above formula (1) can be copolymerized. This monomer includes methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, pentyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, octyl (meth) acrylate Alkyl (meth) acrylates such as vinyl ethers such as butyl vinyl ether and methyl vinyl ether, vinyl acetate, vinyl propionate, vinyl pyrrolidone, vinyl imidazole, vinyl caprolactam, maleic anhydride, hydroxyethyl acrylate, hydroxypropyl acrylate, acrylamide, dimethylacrylamide, Acrylonitrile and the like. These monomers can be copolymerized within a range that does not impair the adhesive strength and cohesive strength of the adhesive.

The basic polymer (B) used in the present invention includes an amino group, an alkylamino group, a pyrrolidone group,
Examples of the polymer include a pyridine group, an imidazole group, a pyrimidine group, a piperazine group and the like. Among these, a polymer having an amino group, an alkylamino group, or a pyrrolidone group is more preferable in view of the strength of interaction with an acidic group, the cohesiveness of the pressure-sensitive adhesive, and the cost of raw materials. Examples of the polymer include condensation polymers such as polyester, polyamide, and polyether, and vinyl polymers such as polyolefin and polystyrene, and vinyl polymers are preferable in view of the solubility and flexibility of the polymer. Specifically, aminoethyl (meth) acrylate, dimethylamino
(Meth) acrylate, diethylaminomethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate, alkylamino (meth) acrylate such as dimethylaminobutyl (meth) acrylate, vinylpyrrolidone,
Homopolymers and copolymers containing vinyl monomers such as vinylpyridine and vinylimidazole can be mentioned.

In the present invention, the acidic group-containing polymer (A)
(A) and (B) such that the acidic group and the basic group of the basic group-containing polymer (B) have a gram equivalent ratio of 1.0: 0.02 to 1.0: 0.80.
It is important to mix The basic group of the polymer (B) is 0.02 in gram equivalent ratio to the acidic group of the polymer (A).
If it is less than 30, sufficient cohesive force cannot be obtained, and adhesive residue tends to be generated when the adhesive is released. On the other hand, when it exceeds 0.80, the adhesive strength required for skin adhesion cannot be obtained, which is not preferable. Further, the more preferable value of the gram equivalent ratio of the acidic group of the acidic group-containing polymer (A) and the basic group of the basic group-containing polymer (B) is 1.0: 0.05 to 1.0: 0.5.

The liquid component (C) used in the present invention is not particularly limited as long as it has compatibility with the polymer (A) and the polymer (B). Among such liquid components, those that are liquid at room temperature are preferred, and specifically,
Glycols such as propylene glycol, polyethylene glycol, polypropylene glycol, poly (oxyethylene-oxypropylene) glycol;
Alcohols such as ethanol and oleyl alcohol; glycerins such as glycerin and triacetin; oils and fats such as olive oil and castor oil; higher fatty acids such as isopropyl myristate, isooctyl palmitate, ethyl oleate and diethyl sebacate Esters; for example, linolenic acid, linoleic acid,
Higher fatty acids such as oleic acid and capric acid; fatty acid esters such as diethyl phthalate, diisopropyl adipate; aprotic polar organic substances such as dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone; lauramide, dimethyl Examples include liquid surfactants such as dodecylsulfoxide, dodecylpyrrolidone and sorbitan monocaprylate, and hydrocarbons such as liquid paraffin. These can be used alone or in combination of one type or two or more types.

Among them, the liquid component (C) of the present invention includes higher fatty acid esters such as isopropyl myristate, isooctyl palmitate and ethyl oleate, and higher fatty acids such as linolenic acid, linoleic acid and oleic acid. Is preferred from the viewpoints of improving the adhesive strength of the gel-like pressure-sensitive adhesive, the ease of peeling, and the percutaneous absorption of the drug, and glycols such as polyethylene glycol, polypropylene glycol, and poly (oxyethylene-oxypropylene) glycol are suitable for sweat absorption and moisture absorption. It is preferable from the viewpoint of suppressing skin irritation by having properties.

In the present invention, the polymer (A), the polymer (B) and the liquid component (C) are the total content of the polymer (A) and the polymer (B) and the content of the liquid component (C). The weight ratio of the quantities is 1.0: 0.25 to 1.0: 2.0, preferably 1.0: 0.4 to 1.
It is mixed at a ratio of 0: 1.2. With such an appropriate mixing ratio, it has an appropriate adhesive force required to prevent detachment from the skin-adhesive surface and an easy-to-peel property that does not damage the skin surface at the time of peeling after use, and has little adhesive residue. A safe gel-like adhesive is obtained. The adhesive residue here means 18 which will be described later.
In the 0 degree peel test, it means a degree to which the liquid component and / or the adhesive polymer do not adhere to the bakelite plate after peeling.

The gel-like pressure-sensitive adhesive of the present invention is obtained by mixing and dissolving the polymer (A), the polymer (B) and the liquid component (C) in a common solvent, for example, in the mixing ratio described in the preceding paragraph, and then dissolving the mixture in a common solvent. It is applied to one surface of the release material, and then the solvent is removed by a drying treatment to form an adhesive layer made of such a gel-like adhesive. The thickness of the completed pressure-sensitive adhesive layer depends on the drug used, for example, when a drug is contained in a gel-type pressure-sensitive adhesive, but is usually 20 μm to 150 μm.
μm, preferably about 30 μm to 80 μm.

The patch of the present invention can be obtained by directly or indirectly laminating the pressure-sensitive adhesive layer comprising the gel-like pressure-sensitive adhesive of the present invention obtained as described above and a support, The gel pressure-sensitive adhesive of the present invention can be obtained by a conventionally known method such as applying the gel pressure-sensitive adhesive directly onto the body using a coater or the like, or transferring a gel pressure-sensitive adhesive layer onto a support.

As the support used in the present invention, the above-mentioned pressure-sensitive adhesive layer can be formed, it is self-retaining, and it is applied to the skin surface to allow the drug to penetrate by percutaneous absorption and to the skin surface. There is no particular limitation as long as it can be used as a patch used for protection and the like. Polyester, polyolefin, polymer film such as cellulose ester, polyester, polyolefin, cellulose ester, polyurethane, woven or knitted fabric composed of polyamide, etc.
A porous film made of nonwoven fabric, paper, polyester, polyolefin, cellulose ester, polyurethane, polyamide, or the like, or a laminate made of one or a combination of two or more thereof can be used. The thickness of these supports is usually from 100 μm to 100
0 μm, preferably 200 μm to 500 μm.

A patch can be prepared by adding a drug to the pressure-sensitive adhesive of the present invention. The drug to be contained is not particularly limited, but specific examples include anti-inflammatory analgesics, steroids, antihypertensive diuretics, anesthetics, antihistamines, antitumor agents, antihypertensives, antidepressants, vitamins, and the like. . The content of the drug is set depending on the purpose of treatment, but is usually 0.1 to 40% by weight, preferably 1 to 30% by weight. When the content is less than 0.1% by weight, transdermal absorption of a drug usually required for treatment may not be obtained. On the other hand, when the content exceeds 40% by weight, the adhesive strength of the patch decreases and the amount of the drug remaining in the patch after use increases, which is uneconomical. In addition, as a method for containing a drug, a drug solution is preliminarily mixed with a solution-type pressure-sensitive adhesive to form a drug-containing pressure-sensitive adhesive layer, or the drug is not contained by a method such as impregnation, transfer, spraying, or the like. Conventionally known methods can be employed depending on the physical properties of the drug to be contained, for example, by allowing the pressure-sensitive adhesive layer not sufficiently containing the drug to contain the drug in an amount sufficient for transdermal absorption.

[0019]

As described above, the pressure-sensitive adhesive of the present invention can be gelled without using a low-molecular crosslinking agent, and can contain a large amount of liquid components. Less delamination. Further, transdermal absorption can be promoted depending on the type of the oily liquid to be contained.

[0020]

EXAMPLES The present invention will be described below with reference to examples. In Examples, parts and% mean parts by weight and% by weight, respectively. Further, “adhesive strength” and “cohesive strength” in the examples were measured by the following methods.

(1) Adhesive force A sample cut to a width of 12 mm and a length of 50 mm was attached to a bakelite plate, and a roller having a load of 850 g was reciprocated once, and allowed to stand in a thermostat at 37 ° C. for 30 minutes. 30
0 mm / min. At a speed of 180 degrees, and the peeling force at that time was defined as the adhesive strength.

(2) Cohesive force After measuring the adhesive force by the method of the above (1), it was visually determined whether or not the adhesive remained on the bakelite plate.

Example 1 Tetraethylene glycol dodecyl ether acrylate 45 under a nitrogen gas atmosphere
g, 50 g of vinyl acetate, 5 g of acrylic acid and 100 g of ethyl acetate, 0.374 g of azobisisobutyronitrile was added as a polymerization initiator, and nitrogen gas was passed through the solution for 1 hour. The temperature was raised to 70 ° C., and a polymerization reaction was performed for 2 hours to obtain an acrylic copolymer having an acidic group. For 60 g of solid content (33% ethyl acetate solution) of this copolymer, polypropylene glycol (number average molecular weight 2000) 40
g, 1.17 g of a dimethylaminoethyl methacrylate copolymer having a basic group (Eudraki Pitt E, manufactured by Roehm Pharma)
(5% ethanol solution) and 180 g of ethanol were added, and this mixed solution was applied onto a silicone-coated release film so that the thickness of the dried pressure-sensitive adhesive layer would be 50 μm, and then at 60 ° C. for 30 minutes. After drying, an adhesive layer was obtained. A 3.5 μm PET film was adhered to one surface of the obtained pressure-sensitive adhesive layer as a support to obtain a pressure-sensitive adhesive tape for a peel test. The tape thus obtained was cut into 12 mm x 50 mm, and the adhesive strength was measured. As shown in Table 1, the adhesive strength was good at 76 g, and no adhesive residue was observed.

Comparative Example 1 An adhesive tape was obtained in the same manner as in Example 1 except that the amount of the dimethylaminoethyl methacrylate copolymer having a basic group was changed to 0.11 g.

Comparative Example 2 An adhesive tape was obtained in the same manner as in Example 1 except that the amount of the dimethylaminoethyl methacrylate copolymer having a basic group was changed to 11.66 g.

Example 2 An adhesive tape was obtained in the same manner as in Example 1 except that the amount of polypropylene glycol was changed to 60 g.

Example 3 The procedure of Example 1 was repeated, except that 2.31 g of polyvinylpyrrolidone was used as the polymer having a basic group instead of the dimethylaminoethyl methacrylate copolymer having a basic group. In the same manner as in Example 1, an adhesive tape was obtained.

Example 4 Tetraethylene glycol dodecyl ether acrylate 30 in a nitrogen gas atmosphere
g, 2-ethylhexyl acrylate 55 g, acrylic acid 15 g, and ethyl acetate 100 g, azobisisobutyronitrile as a polymerization initiator was added in an amount of 0.285 g, and nitrogen gas was passed through the solution for 1 hour. The temperature was raised to 70 ° C., and a polymerization reaction was performed for 2 hours to obtain an acrylic copolymer having an acidic group. 60 g of solid content of this copolymer
After adding 40 g of polypropylene glycol (number average molecular weight 2000), 6.9 g of polyvinyl pyrrolidone having a basic group (5% ethanol solution) and 180 g of ethanol to (33% ethyl acetate solution), the mixed solution was coated with silicone. The resulting pressure-sensitive adhesive layer was coated on the release film so that the thickness of the dried pressure-sensitive adhesive layer was 50 μm, and dried at 60 ° C. for 30 minutes to obtain a pressure-sensitive adhesive layer. A 3.5 μm PET film was adhered to one surface of the obtained pressure-sensitive adhesive layer as a support to obtain a pressure-sensitive adhesive tape for a peel test.

Comparative Example 3 An adhesive tape was obtained in the same manner as in Example 4 except that polyvinylpyrrolidone having a basic group and ethanol were not added.

Example 5 An adhesive tape was obtained in the same manner as in Example 4, except that 2.76 g of polyvinylpyrrolidone was used, and isopropyl myristate was used instead of polypropylene glycol.

Comparative Example 4 An adhesive tape was obtained in the same manner as in Example 5 except that polyvinylpyrrolidone and ethanol were not added.

Example 6 An adhesive tape was obtained in the same manner as in Example 5, except that 2 g of ketoprofen was added as a drug to the mixed solution of the adhesive. This adhesive tape was evaluated for drug permeability as well as adhesive strength and cohesive strength. A pressure-sensitive adhesive tape obtained by laminating a PET film as a support was punched out at 16.5 mmΦ to obtain a test piece. Ethylene vinyl acetate polymer film (vinyl acetate 7 mol%, film thickness 4) between donor and acceptor of vertical diffusion cell
5 μm), and a test piece was attached to the donor side of the film. The acceptor was filled with 20 ml of a pH 7.4 phosphate buffer. The diffusion cell was set in a thermostat at 37 ° C. and stirred with a magnetic stirrer. Six hours later, the liquid on the acceptor side was sampled, the drug concentration was analyzed by liquid chromatography, and the amount of permeation of the drug was measured. The experiment was repeated four times with the same sample, and the average value was defined as the permeation amount of the sample. The permeation amount of the drug (ketoprofen) in this test piece was as good as 52 μg / cm2 / 6hr.

[0033]

[Table 1]

Claims (4)

[Claims] An acidic group-containing polymer (A) containing 1 to 40% by weight of a carboxyl group-containing ethylenically unsaturated monomer and 20 to 90% by weight of a monomer represented by the following general formula (1): It comprises a basic group-containing polymer (B) and a liquid component (C) compatible with both polymers, and the total content of (A) and (B) and the content weight ratio of (C) are 1.0: 0.25.
~ 1.0: 2.0 gel adhesive. CH2 = C (R1) COO (CH2CH (R2) O) nR3 Formula (1) (where R1 and R2 are hydrogen or methyl groups, and n is 2 or more and 1
An integer of 0 or less, R3 represents an alkyl group having 6 to 24 carbon atoms. ) 2. The gram equivalent ratio of the acidic group of the acidic group-containing polymer (A) to the basic group of the basic group-containing polymer (B).
2. The gel-like pressure-sensitive adhesive according to claim 1, wherein (A) and (B) are blended so as to be 1: 0.02 to 1: 0.80. 3. The gel-like adhesive according to claim 1, wherein the basic polymer (B) is selected from polyvinylpyrrolidone, vinylpyrrolidone copolymer, and diethylaminomethylmethacrylate copolymer. Agent. 4. A patch comprising the pressure-sensitive adhesive according to claim 1 containing a drug.