JP2000038337A - New plaster - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new plaster and a plaster pharmaceutical preparation without requiring a support good in homogeneity of the surface of a tacky agent in the plaster and plaster pharmaceutical preparation comprising a new tacky agent different in tack strength of the tacky agent between the front and back sides and having substantially no tack strength in either one of the front and back sides. SOLUTION: This plaster comprises a tacky agent obtained by adding a poor solvent for a perfluoroalkyl (meth)acrylate copolymer (B) prepared by copolymerizing 25-85 wt.% of a perfluoroalkyl (meth)acrylate with 10-75 wt.% of at least one ingredient contained in a tacky polymer (A) to a polymer solution obtained by blending (1) the tacky polymer (A) with (2) the copolymer (B) in (7:3) to (1:9) ratio of the tacky polymer A: copolymer B and forming a film.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a patch comprising a pressure-sensitive adhesive blended with perfluoroalkyl (meth) acrylate. More specifically, the present invention relates to a patch and a patch which do not necessarily require a support because the pressure-sensitive adhesive has different adhesive strengths on the front and back sides and has substantially no adhesive strength.

[0002]

2. Description of the Related Art In recent years, various transdermal patches have been developed for administering drugs into the living body through the skin surface. These transdermal patches comprise a pressure-sensitive adhesive layer and a support, and a non-woven fabric or a polymer film is used as the support. However, conventional percutaneous absorption patches using these supports have problems in that the patch is peeled off and skin irritation is likely to occur due to the ability to follow the expansion and contraction of the skin.

[0003] In order to improve these, a method using a flexible support is disclosed in Japanese Patent Application Laid-Open Nos. Hei 5-38931 and Hei 6-142178, but the elastic modulus of the polymer used for the support is disclosed. Is larger than the pressure-sensitive adhesive layer, so the problem of skin irritation has not been solved.

[0004] In addition, as an adhesive which does not require a support, an incompatible blend is formed by using an acrylic polymer and an acrylic polymer and an incompatible fluorine polymer, whereby a gradient structure is developed, and the adhesive is adhered on both sides of the adhesive. It is known that pressure sensitive adhesives with different properties can be obtained (Abstracts of the 35th Annual Meeting of the Adhesive Society of Japan, p5-8 (1997)).

[0005]

However, the formation of a gradient structure using the above incompatible polymer blend is greatly limited by the type of polymer used and the film forming conditions, and the formation of the gradient structure is not easy. was there.

Further, Japanese Patent Publication No. 60-56686 discloses a pressure-sensitive adhesive in which a perfluoroalkyl (meth) acrylate is blended, but does not show that the pressure-sensitive adhesive has different tackiness on the front and back sides. JP-B-60-56686 also discloses and suggests a pressure-sensitive adhesive obtained by blending the pressure-sensitive adhesive polymer (A) of the present invention with a perfluoroalkyl (meth) acrylate copolymer (B). Not.

[0007] That is, an object of the present invention is to provide a patch and a patch preparation comprising a novel pressure-sensitive adhesive having different pressure-sensitive adhesive forces on the front and back, and substantially no pressure on one of the front and back.

Another object of the present invention is to provide a patch and a patch preparation comprising a novel pressure-sensitive adhesive having different adhesive strengths on the front and back sides and substantially no adhesive strength on one side, and requiring no support. To provide.

It is a further object of the present invention to provide a novel patch and adhesive which can be easily obtained, having different adhesive strengths on the front and back sides of the pressure-sensitive adhesive and having substantially no adhesive strength on one of the front and back sides and requiring no support. It is to provide a formulation.

[0010] Still another object of the present invention is to provide a patch and a patch comprising a novel pressure-sensitive adhesive having different pressure-sensitive adhesive forces on the front and back, and substantially no pressure on one of the front and back.
An object of the present invention is to provide a patch and a patch preparation which do not require a support having good uniformity on the surface of the pressure-sensitive adhesive.

The inventors of the present invention have conducted intensive studies to achieve such an object, and as a result, have found that a perfluoro (meth) acrylate obtained by copolymerizing an adhesive polymer and at least one component contained in the adhesive polymer. It was found that the object of the present invention was achieved by adding a poor solvent of perfluoro (meth) acrylate copolymer to a polymer solution obtained by blending with a copolymer and forming a film, thereby completing the present invention. I came to.

[0012]

That is, the present invention provides:
(1) adhesive polymer (A) and (2) perfluoro
25% to 85% by weight of (meth) acrylate and at least one component 1 of the components contained in the adhesive polymer (A)
A perfluoroalkyl (meth) acrylate copolymer (B) copolymerized with 0 to 75% by weight,
In a polymer solution blended in a ratio of 7: 3 to 1: 9,
It is intended to provide a patch comprising an adhesive formed into a film by adding a poor solvent for the copolymer (B), and a patch preparation comprising a drug in the adhesive.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The adhesive polymer (A) used in the present invention can be basically used without any limitation as long as it has adhesiveness to the skin. Specifically, for example, a polyacrylate-based adhesive polymer,
Examples thereof include a polyvinyl acetate-based adhesive polymer and a rubber-based adhesive polymer.

Preferred specific examples include, for example, polyacrylic ester-based adhesive polymers and polyvinyl acetate-based adhesive polymers, and one or more selected from such adhesive polymers. Things can be used.

Here, the polyacrylate-based adhesive polymer is an alkyl (meth) acrylate containing as a main component an alkyl (meth) acrylate having 1 to 20 carbon atoms and containing 10% by weight or less of acrylic acid. Ester copolymers are preferred. Among them, a copolymer containing 2-ethylhexyl acrylate as a main component is particularly preferable from the viewpoint of adhesive strength.

As the polyvinyl acetate-based adhesive polymer, a copolymer containing vinyl acetate as a main component and containing 10% by weight or less of acrylic acid is preferable from the viewpoint of adhesive strength and cohesive strength.

The perfluoroalkyl (meth) acrylate copolymer (B) used in the present invention contains 25% by weight (hereinafter, referred to as perfluoroalkyl (meth) acrylate).
% May be described as “wt”) to 85% by weight (wt)
%, At least one of the components contained in the following adhesive polymer is copolymerized with 10% by weight (wt)% to 75% by weight (wt)%.

In the perfluoroalkyl (meth) acrylate copolymer (B), if the perfluoroalkyl (meth) acrylate is less than 25% by weight, it is not possible to substantially eliminate the adhesive force of one of the front and back of the pressure-sensitive adhesive,
It is difficult to obtain adhesives having different adhesive strengths on the front and back.
On the other hand, the perfluoroalkyl (meth) acrylate
If the content is more than wt%, the solubility or compatibility of the perfluoroalkyl (meth) acrylate copolymer with the adhesive polymer dope becomes poor, and it is difficult to obtain a homogeneous adhesive polymer dope, which is not preferable.

In the perfluoroalkyl (meth) acrylate copolymer (B) of the present invention, at least one of the components contained in the following tacky polymer (A) contains 1
It is important that the copolymer is copolymerized at a ratio of 0 wt% to 75 wt%. If the copolymerization ratio is less than 10% by weight, the compatibility between the perfluoroalkyl (meth) acrylate copolymer (B) and the adhesive polymer (A) becomes poor, and it becomes difficult to obtain adhesives having different adhesive strengths on the front and back. In addition, the cohesive force of the pressure-sensitive adhesive is reduced, and adhesive residue is likely to be generated, which is not preferable. On the other hand, if the copolymerization ratio exceeds 75% by weight, the difference in the adhesive strength between the front and back of the pressure-sensitive adhesive is less likely to appear.

The perfluoroalkyl (meth) acrylate used in the present invention is, for example, 2-perfluorooctylethyl (meth) acrylate, 2-perfluorohexylethyl (meth) acrylate, 2-perfluorodecylethyl (meth) acrylate , 2-perfluorododecylethyl (meth) acrylate, perfluoroheptylmethyl (meth) acrylate, 1,1,1,3,3,3-hexafluoroisopropyl (meth) acrylate and the like.

Among these, the perfluoroalkyl (meth) acrylate of the present invention is preferably a compound having 2 to 18 carbon atoms.
Perfluoroalkyl (meth) acrylate comprising an alkyl group of the above is preferred, and perfluoroalkyl (meth) acrylate comprising an alkyl group having 6 to 12 carbon atoms is particularly preferred.

Further, at least one of the components contained in the adhesive polymer (A) used in the perfluoroalkyl (meth) acrylate copolymer (B) of the present invention is, for example, a (meth) acrylate having 1 to 20 carbon atoms. ) Acrylic acid alkyl esters, vinyl acetate, etc., of which 2-ethylhexyl acrylate is particularly preferred.

Accordingly, the perfluoroalkyl of the present invention
Perfluoro constituting (meth) acrylate copolymer
As a preferred combination of the (meth) acrylate and at least one component contained in the adhesive polymer (A), the former is a perfluoroalkyl (meth) acrylate comprising an alkyl group having 2 to 18 carbon atoms, and the latter is a Carbon number 1
-20 (meth) acrylic acid alkyl ester, vinyl acetate, etc., in particular, the former is a perfluoroalkyl (meth) acrylate comprising an alkyl group having 6 to 12 carbon atoms, and the latter is 2-ethylhexyl acrylate. Particularly preferred combinations can be mentioned.

In this case, the mixing ratio of the perfluoro (meth) acrylate to at least one of the components contained in the adhesive polymer (A) is from 25% by weight to 8%.
It is preferred that the latter is copolymerized at 5% by weight and the latter at 10% to 75% by weight.

In the present invention, it is important that the adhesive polymer (A) and the perfluoroalkyl (meth) acrylate copolymer (B) are blended in a ratio of A: B = 7: 3 to 1: 9. . If the ratio of the adhesive polymer exceeds 70% by weight, the difference in adhesive strength between the front and back of the pressure-sensitive adhesive layer is less likely to be exhibited, and it is difficult to obtain a pressure-sensitive adhesive having substantially no adhesive strength between the front and back. . On the other hand, if the amount of the adhesive polymer is less than 10% by weight, sufficient adhesive strength to the skin cannot be obtained, which is not practical.

In the present invention, a poor solvent for the copolymer (B) is added to a polymer solution in which the adhesive polymer (A) and the perfluoro (meth) acrylate copolymer (B) are blended to form a film. It is important to. The perfluoro
By adding a poor solvent for the (meth) acrylate copolymer to the polymer solution in which the adhesive polymer and the perfluoro (meth) acrylate copolymer are blended, the adhesive has different adhesive properties on the front and back of the adhesive. An adhesive having good surface uniformity can be obtained. Although the mechanism is not clear, the addition of a poor solvent of perfluoro (meth) acrylate copolymer increases the phase separation rate of the blended polymer, and the phase homogenization is achieved by spinodal decomposition from nucleus growth. It is estimated that a pressure-sensitive adhesive having good properties can be obtained. Examples of the solvent of the polymer solution in which the adhesive polymer (A) and the perfluoro (meth) acrylate copolymer (B) are blended include ethyl acetate, tetrahydrofuran, methyl ethyl ketone, and N-methylpyrrolidone. The poor solvent for the perfluoro (meth) acrylate copolymer is defined as the perfluoro (meth) acrylate when 2 g of the liquid component is added to 1 g of the perfluoro (meth) acrylate copolymer solution at 10% by weight. The copolymer is a liquid component that precipitates and precipitates, for example, hexane, cyclohexane, heptane, toluene,
Xylene and the like can be mentioned.

The amount of the perfluoro (meth) acrylate copolymer poor solvent to be added depends on the copolymer composition of the perfluoro (meth) acrylate copolymer and the blending ratio with the tacky polymer. Although it cannot be determined, the adhesive polymer and the perfluoro (meth) acrylate copolymer blended in a polymer solution of 15 to
It is preferable to add so as to be 70 wt%. When the amount of the poor solvent is less than 15% by weight, it is difficult to obtain a pressure-sensitive adhesive having characteristics that the pressure-sensitive adhesive has different adhesive properties on the front and back surfaces and has good surface uniformity. If it exceeds 70% by weight, the viscosity of the polymer solution decreases, and it becomes difficult to control the thickness of the pressure-sensitive adhesive at the time of forming the pressure-sensitive adhesive, which is not preferable.

The patch of the present invention comprises the above-mentioned adhesive polymer (A), 25% to 85% by weight of perfluoroalkyl (meth) acrylate, and components contained in the adhesive polymer (A). 10% by weight of at least one component of
A: B = 7: 3 with a perfluoroalkyl (meth) acrylate copolymer (B) obtained by copolymerizing the polymer with a polymer having a ratio of
It can be obtained by blending at a ratio of 例 え ば 1: 9, for example, applying this adhesive solution onto a silicone-coated release film and drying. The pressure-sensitive adhesive of the present invention thus obtained has a substantially different pressure-sensitive adhesive force between the front and back sides of the pressure-sensitive adhesive, and the pressure-sensitive adhesive of the present invention can be used without providing a support as it is. it can.

As described above, the pressure-sensitive adhesive of the present invention has different pressure-sensitive adhesive strength between the front and back surfaces, but the pressure-sensitive adhesive force on the surface opposite to the surface having substantially no pressure-sensitive adhesive force is preferably 40 g or more and 500 g or less.

If necessary, such a patch may be provided with, for example, a protective layer or the like for assisting the simplicity of handling, and the pressure-sensitive adhesive layer of the present invention and / or other pressure-sensitive adhesive layers or drugs. A plurality of pressure-sensitive adhesive layers using a release control layer or the like may be used.

The adhesive preparation of the present invention can be prepared by incorporating a drug into the 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 the treatment, and is usually 0.1 to 40 wt%, preferably 1 to 30 wt%.
t%. If the content is less than 0.1 wt%, transdermal absorption of the drug in an amount 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, such as by allowing the pressure-sensitive adhesive layer not sufficiently containing to contain the drug in an amount sufficient for transdermal absorption.

Further, conventionally known drug dissolution aids, absorption promoters, stabilizers, antioxidants, fragrances, preservatives, pH adjusters, and the like can be added to the pressure-sensitive adhesive of the present invention, if necessary. . Specifically, for example, polyhydric alcohols such as propylene glycol, hexanetriol, glycerin, polyethylene glycol, polypropylene glycol, and poly (oxyethylene-oxypropylene) glycol; for example, monoacetin, triacetin, glycerin triisooctanoate, and sorbitan monocaprylate And polyhydric alcohol derivatives such as sorbitan monooleate; oils and fats such as olive oil and castor oil; higher fatty acid esters such as isopropyl myristate, isooctyl palmitate, ethyl oleate and diethyl sebacate; Higher fatty acids such as linoleic acid, oleic acid and capric acid; fatty acid esters such as diethyl phthalate and diisopropyl adipate; Aprotic polar organic substances such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone; absorption promoters and solubilizers such as hydrocarbons such as liquid paraffin; and magnesium stearate, zinc stearate and citric anhydride. Stabilizers such as, for example, ascorbic acid,
Antioxidants such as tocopherol acetate and vitamin E, for example, fragrances such as menthol, camphor, peppermint oil and lemon oil, for example, preservatives such as dibutylhydroxytoluene, isobutyl parahydroxybenzoate, for example, sodium citrate, dihydrogen citrate PH adjusters such as sodium, sodium hydrogen phosphate, sodium hydrogen phosphate and the like can be mentioned. These may be used alone or in combination of two or more.
Mixtures of more than one species can also be used.

[0033]

As described above, a polymer solution obtained by blending a tacky polymer and a perfluoro (meth) acrylate copolymer obtained by copolymerizing at least one of the components contained in the tacky polymer is added to the perfluoro (meth) acrylate solution. By adding a poor solvent of (meth) acrylate copolymer to form a film, it is easy to obtain an adhesive with different adhesive strength on the front and back and good uniformity of the adhesive surface, and unnecessary adhesion of the support And patch preparations.

[0034]

EXAMPLES The present invention will be described below with reference to examples. In Examples, parts and% mean parts by weight and% by weight, respectively. In the examples, "adhesive strength" and "surface uniformity" were measured by the following methods.

(1) Adhesive Strength A sample cut to a width of 12 mm and a length of 50 mm was attached to a bakelite plate, 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 (1), it was visually determined whether or not the adhesive remained on the Bakelite plate.

(3) Surface homogeneity The pressure-sensitive adhesive layer was attached to a glass plate, and the transmittance of light transmitted from the back surface of the pressure-sensitive adhesive layer to the surface was visually determined. If the intensity of the transmitted light was not uneven on the surface of the pressure-sensitive adhesive, the surface was judged to be homogeneous.

Example 1 Under a nitrogen gas atmosphere, azobisisobutyronitrile was used as a polymerization initiator in a solution of 40 g of 2-perfluorooctylethyl methacrylate, 45 g of 2-ethylhexyl acrylate, 15 g of acrylic acid, and 100 g of ethyl acetate. After adding 0.4 mol% of the total monomer, nitrogen gas was passed through the solution for 1 hour.
Polymerization was performed for a period of time to obtain a perfluoroalkyl methacrylate copolymer. Similarly, a polyacrylic acid alkyl ester copolymer comprising 90 parts of 2-ethylhexyl acrylate, 7 parts of methyl methacrylate, and 3 parts of acrylic acid was obtained. 23.4 g of a 28.5% perfluoroalkyl methacrylate copolymer in ethyl acetate solution, 10% polyalkyl acrylate copolymer in ethyl acetate solution 6
A solution containing 0 g and 73.3 g of toluene as a poor solvent was applied to a silicone-coated release film with a thickness of 50 mil and dried at 60 ° C. for 30 minutes to obtain an adhesive layer.

Comparative Example 1 An adhesive layer was obtained in the same manner as in Example 1, except that ethyl acetate was used instead of toluene. The adhesive force on the front side (air side) is practically nil, and the adhesive force on the back side (release film side) is 214 g /
It was 12 mm. However, the light transmittance of the obtained pressure-sensitive adhesive layer was not uniform.

Comparative Example 2 An adhesive layer was obtained in the same manner as in Example 1 except that toluene was not added. The surface side (air side) had substantially no adhesive force, and the back side (release film side) had an adhesive force of 221 g / 12 mm. However, the light transmittance of the obtained pressure-sensitive adhesive layer was not uniform.

Comparative Example 3 Example 1 was repeated except that tetrahydrofuran was used instead of toluene.
In the same manner as in the above, an adhesive layer was obtained. The adhesive force on the front side (air side) is practically nil, and the adhesive force on the back side (release film side) is 2
It was 34 g / 12 mm. However, the light transmittance of the obtained pressure-sensitive adhesive layer was not uniform.

Example 2 In a nitrogen gas atmosphere, azobisisobutyronitrile was added to a solution of 60 g of 2-perfluorooctylethyl methacrylate, 25 g of 2-ethylhexyl acrylate, 15 g of acrylic acid and 100 g of ethyl acetate to initiate polymerization by adding After adding 0.5 mol% of the total of the monomers, nitrogen gas was passed through the solution for 1 hour, and then polymerization was carried out at 70 ° C. for 5 hours to obtain a perfluoroalkyl methacrylate copolymer. It contains 23.4 g of an ethyl acetate solution of a 28.5% perfluoroalkyl methacrylate copolymer, 60 g of an ethyl acetate solution of a 10% alkyl polyacrylate copolymer used in Example 1, and 73.3 g of cyclohexane as a poor solvent. The solution is applied on a silicone-coated release film to a thickness of 50 mils,
After drying for a minute, an adhesive layer was obtained. The obtained pressure-sensitive adhesive was cut into a width of 12 mm and a length of 50 mm to obtain a sample for measuring the adhesive strength. The surface side (air side) was affixed to a bakelite plate to measure the adhesive strength, but no measurement was possible due to lack of adhesive strength. When the back side was adhered to a bakelite plate and the adhesive strength was measured, it was 291 g /
It was as good as 12 mm and the cohesion was good. In other words, a pressure-sensitive adhesive having no support was obtained, since the adhesive force was different between the front and back surfaces of the pressure-sensitive adhesive. In addition, the obtained adhesive layer had a uniform light transmittance, and the surface of the adhesive layer was uniform.

[0043]

[Table 1]

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Takeyuki Kawaguchi 2-1 Hinodemachi, Iwakuni-shi, Yamaguchi F-term in Iwakuni Research Center Teijin Limited 4C076 AA74 BB31 DD34 DD45 DD48 DD64 EE07A EE09A EE10A EE12A EE48A FF67 4C081 AA03 AA12 BB04 BC02 CA051 CA081 CC01 DA02 DC12

Claims (5)

[Claims] 1. An adhesive polymer (A) and (2)
A perfluoroalkyl (meth) acrylate obtained by copolymerizing 25% to 85% by weight of perfluoro (meth) acrylate and 10% to 75% by weight of at least one component contained in the adhesive polymer (A). An adhesive formed by adding a poor solvent of the copolymer (B) to a polymer solution obtained by blending the polymer (B) with A: B at a ratio of 7: 3 to 1: 9. Patch. 2. The pressure-sensitive adhesive polymer (A) has 1 to 1 carbon atoms.
The patch according to claim 1, which is an acrylic polymer mainly composed of an alkyl (meth) acrylate 20 or a vinyl acetate polymer mainly composed of vinyl acetate. 3. The adhesive patch according to claim 1, wherein the adhesive has substantially no adhesive strength on one side and an adhesive strength on the other side of 40 g or more and 500 g or less. 4. The patch according to any one of claims 1 to 3, which does not have a support and consists essentially of the pressure-sensitive adhesive. 5. The patch preparation according to claim 1, wherein the adhesive contains a drug.