JPH05279251A - Patch using a breathable support - Google Patents

Abstract

(57) [Summary] [Purpose] To provide a patch having an appropriate moisture permeability by forming through-holes having a controlled pore size and pore density in a support. A patch having a drug-containing pressure-sensitive adhesive layer formed on one surface of a synthetic resin film support, wherein the support is preliminarily laser-processed with through holes having a pore size of 0.1 to 60 μm. A large number of holes are formed to have a pore density of 1 to 50%, and the moisture permeability of the entire patch is 100 to 500 g / m ² · 2.
It is said to be 4 hours.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a patch using a moisture-permeable support.

[0002]

2. Description of the Related Art A patch having a drug-containing pressure-sensitive adhesive layer provided on one side of a support or a drug matrix layer and a pressure-sensitive adhesive layer formed on one side of a support for the purpose of local or systemic effect of the drug. The applied patch is used.

Nonwoven fabrics, synthetic resin films and the like are used as the support for such patches. Since the support made of a synthetic resin film does not allow water vapor and a drug to pass therethrough, a occlusive bandage therapy effect can be obtained and the drug can be effectively absorbed. However, when a support made of such a material is used, skin damage due to stuffiness is also likely to occur. Therefore, a support made of a material having relatively high moisture permeability such as polyurethane is used, or the support is made thin by making the support thin or making a hole.

However, in the case of polyurethane or a thin film, there is a drawback that the adhesives stick to each other during application, or they are not evenly applied and wrinkle because they are not elastic (not self-supporting).

A patch using a support having a hole in the film is disclosed in, for example, Japanese Patent Application Laid-Open No. 2-221218 and Japanese Patent Application Laid-Open No. 57-64613.
However, among the methods of porosity used for the above-mentioned patch, the method by melt drawing has a wide distribution in the size of voids, and it is difficult to adjust the porosity. Therefore, it is difficult to control the water vapor transmission rate of the film, and if the voids are too large, the pressure-sensitive adhesive will exude.

Further, synthetic resins which can be made porous by stretching are mainly of polyolefin type, and other synthetic resins are not suitable for making porous by stretching. A method of adding a filler or a foaming agent to a synthetic resin in advance to form a film, and then performing a treatment such as stretching, extraction, and heat foaming to make it porous is a method of making the pore diameter and the pore density higher than that made by only stretching. Easy to control. However, for that purpose, it is necessary to uniformly disperse the additives in the synthetic resin using a surfactant, which cannot be controlled without know-how and technology, and complicated pretreatment and posttreatment are required. Become.

Further, the film made porous by each of the above methods has not only through holes but also holes that do not penetrate, that is, do not contribute to moisture permeability, so that the strength of the film is weakened. In addition, it is difficult to make holes having a diameter of several μm or less by the method of making holes by using a needle to make them porous.

On the other hand, a patch using a non-woven fabric as a support is
Although it has very good moisture permeability, it has a drawback in that the effect of occlusive bandage therapy cannot be obtained.

[0009]

SUMMARY OF THE INVENTION The present invention is intended to solve the above-mentioned conventional drawbacks, and its object is to:
The purpose of the present invention is to provide a patch having an appropriate moisture permeability by forming through holes in the support, the through holes of which the pore diameter and the pore density are controlled. Thereby, it is possible to effectively evaporate the water generated by perspiration, prevent skin damage from occurring, and effectively use the drug due to the effect of the occlusive bandage therapy.

[0010]

The present invention consists of the following two. The patch using the moisture-permeable support according to claim 1 is a patch in which a drug-containing pressure-sensitive adhesive layer is formed on one surface of a synthetic resin film support, and the support is preliminarily laser-processed. Therefore, a large number of through holes having a pore diameter of 0.1 to 60 μm are formed so that the pore density is 1 to 50%, and the moisture permeability of the entire patch is 100 to 500 g / m ² · 24 hr. And The patch using the moisture-permeable support according to claim 2, wherein a laminated body of a synthetic resin film and a non-woven fabric or a woven fabric is used as a support, and a drug-containing pressure-sensitive adhesive layer is formed on the synthetic resin film side of the support. The prepared patch, which has a pore size of 0.1 to 6 by laser processing in advance.
A large number of 0 μm through-holes are provided so that the hole density is 1 to 50%, and the moisture permeability of the entire patch is 100 to 500 g / m.
Made with ² · 24 hr or wherein the are.

The above objects are achieved by the above. The invention described in claim 1 will be described below. As the synthetic resin film used for the support of the patch of the present invention,
For example, polyethylene, polybutene, polypropylene,
Olefin-based synthetic resins such as polyisoprene and polybutadiene, styrene-isoprene-styrene block (SI
S) copolymer, styrene-butadiene-styrene block copolymer, styrene-ethylene-butadiene-styrene block copolymer, (meth) acrylic acid alkyl ester, cellulose acetate, ethyl cellulose, polyethylene terephthalate (PET), plasticized acetic acid Examples of the film include vinyl-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane, polyvinylidene chloride, and silicone resin.

As the support used in the present invention, for example, a single layer of the above-mentioned synthetic resin film or a film laminate of two or more sheets, which is preliminarily perforated with a large number of through holes by laser processing, is used. To be done. The pore diameter of the through-hole is limited to the range of 0.1 to 60 μm, because if the pore diameter is small, sufficient moisture permeability cannot be obtained, and if it is large, the pressure-sensitive adhesive exudes. Further, if the pore density of the through-holes is small, sufficient moisture permeability cannot be obtained, and if it is large, the moisture permeability becomes large and the effect of occlusive bandage therapy cannot be obtained.
Is limited to the range of 50%.

The term "pore density" as used herein is a numerical value indicating the proportion (%) of the pore volume in the total volume of the support. The pore diameter and the pore density are measured with a porosity meter by a mercury porosimetry method (a method of measuring porosity and pore diameter by press-fitting amount of mercury and press-fitting pressure).

By using laser processing as a method for making the support porous, it is possible to open cylindrical through-holes having a uniform pore diameter so as to have a predetermined pore density, so that it is possible to control the moisture permeability. It is easy, and the film strength does not decrease as compared with the conventional porosity processing method. Further, the laser processing has an advantage that it is not necessary to perform complicated pretreatment and posttreatment on an object to be processed, and any kind of synthetic resin can be made porous, and no special know-how is required.

Depending on the purpose, various adhesives such as a synthetic resin film having good adhesion with an adhesive, a synthetic resin film made of a material having no drug migration, and a synthetic resin film made of a material having good drug stability can be used as a support. The moisture permeability can be controlled by selecting a film suitable for the composition and drug composition and making it porous by laser processing.

Examples of the pressure-sensitive adhesive used in the present invention include (meth) acrylic acid alkyl ester (co) polymers; styrene-isoprene-styrene block copolymers, styrene-butadiene rubber, polybutene, polyisoprene, butyl rubber, Examples thereof include rubber-based polymers such as natural rubber; and those containing a silicone-based polymer as a main component.
Examples of the monomer capable of forming the (meth) acrylic acid alkyl ester (co) polymer include (meth) acrylic acid alkyl ester and a polymerizable monomer copolymerizable therewith.

Examples of the (meth) acrylic acid alkyl ester include (meth) acrylic acid alkyl esters having an alkyl group with 1 to 18 carbon atoms, such as methyl (meth) acrylate, ethyl (meth) acrylate, and the like.
Butyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, dodecyl (meth) acrylate and the like can be used.

Examples of the polymerizable monomer include (meth) acrylic acid, vinylpyrrolidone, diacetone acrylamide, (poly) ethylene glycol (meth) acrylate, (poly) propylene glycol (meth) acrylate, and 2-hydroxy. Ethyl (meth) acrylate, vinyl acetate, styrene, etc. can be used. The (meth) acrylic acid alkyl ester (co) polymer is prepared by a usual polymerization method such as solution polymerization or bulk polymerization.

If desired, tackifiers, antioxidants, liquid rubbers, softeners, antioxidants, colorants, fillers and the like may be added to the above-mentioned pressure-sensitive adhesives.

The drug contained in the pressure-sensitive adhesive layer in the present invention is not particularly limited as long as it is a drug that can be absorbed through the skin. For example, a non-steroidal anti-inflammatory agent,
Examples include corticosteroids, antihistamines, antipruritic agents, antihypertensive agents, anesthetics, antifungal agents, antiepileptic agents, coronary vasodilators, hormones, muscle relaxants, antiphlogistic / analgesics and local stimulants.

Examples of the above-mentioned non-steroidal anti-inflammatory agents include piroxicam, phenylbutazone, acetylsalicylic acid, flufenamic acid, ibuprofen, ketoprofen, flurbiprofen, sulindac, indomethacin, diclofenac, amphenac, fenbufen, tinolidine, and emorfazone. Is mentioned. Examples of corticosteroids include pretonisolone and clobetasol propionate.

Examples of the antihistamine include diphenhydramine, diphenylimidazole, chlorpheniramine and the like.

Antipruritic agents include, for example, crotamiton, and antihypertensive agents include, for example, clonidine, nifedipine, propranol, and the like.

The anesthetics include lidocaine, benzocaine and the like, the antifungal agents include clotrimazole, pentamycin and the like, and the antiepileptic agents include nitrozebam, meprobamate and the like.

Examples of coronary vasodilators include nitroglycerin, isosorbide dinitrate and the like, and examples of hormone agents include estradiol and the like.

Examples of the muscle relaxant include eperisone hydrochloride and the like, and examples of the anti-inflammatory / analgesic include methyl salicylate, glycol salicylate, glycyrrhizinic acid, glycyrrhetinic acid, borneol, abacus powder and berberyl hydrochloride.

Examples of the topical stimulants include capsicum (capsicum, extract, tincture), capsaicin, nonyl acid vanillyl amide, turpentine oil, dl-camphor, benzyl nicotinate, β-butoxyethyl nicotinate, and peppermint oil,
1-menthol, eucalyptus oil and the like.

The patch of the present invention is prepared, for example, by the following method. First, a large number of through holes are previously formed in the synthetic resin film by laser processing to form a support.

Next, a solution or dispersion containing a pressure-sensitive adhesive, a drug, and, if necessary, an absorption aid, is prepared, and the solution or dispersion is applied to one surface of the above-mentioned support and dried to apply the patch of the present invention. An agent is obtained. A suitable organic solvent or water is used as the solvent of the solution or dispersion.

Further, instead of using the solution or dispersion, a method of heating and melting a mixture of the above-mentioned pressure-sensitive adhesive, drug and absorption aid, and coating this on a support is also adopted. Furthermore, a method may be used in which the above solution, dispersion or melt is applied onto a suitable release paper, dried and then a support is brought into close contact with it. The release paper is used for the purpose of protecting the pressure-sensitive adhesive layer, and a polyester film, a polyethylene-coated high-quality paper, a polyolefin-coated glassine paper, a polypropylene film, or the like on one side of which a silicone release treatment is performed can be used.

The drug is uniformly dispersed or dissolved in the pressure-sensitive adhesive layer, and the thickness thereof is usually about 30 μm-2.
The range of mm is preferred.

When the patch of the present invention has a low moisture permeability, it tends to cause rash and redness of the skin due to stuffiness when the patch is applied to the skin surface. 500 g / m ² · 24 hr
It is limited to the range of. The materials of the support and the pressure-sensitive adhesive are selected so that the moisture permeability of the obtained patch is within the above range, and the thickness of the support and the pressure-sensitive adhesive are further determined.

The above-mentioned moisture permeability is a value measured in accordance with the moisture permeability test method (cup method) of the moisture-proof packaging material of JIS Z0208.

A specific example of the patch of the present invention is S
IS film (styrene-isoprene-styrene block copolymer film, thickness 60 μm) made porous by laser processing (pore diameter 2-3 μm, pore density 20%,
A moisture permeability of 1400 g / m ² · 24 hr) is used as a support, and an acrylic pressure-sensitive adhesive layer having a thickness of 50 μm is formed on one side of this support to obtain a moisture permeability of 300 g / m ² · 24.
It can be adjusted to hr.

Next, the invention according to claim 2 will be described. As the support used in the present invention, a single layer of a synthetic resin film, or a laminated body in which a nonwoven fabric or a woven fabric is laminated with a synthetic resin film laminate of two or more layers is used. As the synthetic resin film, the one used in the invention described in claim 1 is suitable, and the film used is one which has been preliminarily perforated with a large number of through holes by laser processing.

The through hole formed by laser processing has a hole diameter of 0.1 to 60 μm for the same reason as in the first aspect of the invention.
The holes are formed to have a hole density in the range of 1 to 50%.

The above-mentioned non-woven fabric or woven fabric is not particularly limited, and, for example, those made of synthetic fibers such as polypropylene and polyester and those made of natural fibers such as cotton can be used.

The synthetic resin film which has been made porous by the laser processing is, for example, an acrylic or rubber adhesive,
Alternatively, a laminate is obtained by laminating with a non-woven fabric or a woven fabric by adhesion with a solvent-based, curing-based or hot-melt-based adhesive, or heat fusion. When a laminate is obtained by adhesion or heat fusion, it is possible to prevent the through hole from being blocked by laminating the synthetic resin film in a spot shape rather than laminating a non-woven fabric or a woven fabric over the entire surface. Therefore, it is preferable. Further, in the case of heat fusion, it is preferable to heat the non-woven fabric side or the woven fabric side. As the pressure-sensitive adhesive in the present invention, the one used in the invention of claim 1 is preferably used.

Examples of the drug contained in the pressure-sensitive adhesive layer in the present invention include those used in the invention of claim 1. In the present invention, a solution or dispersion containing an adhesive, a drug and, if necessary, an absorption aid and the like is prepared by the same method as in the invention of claim 1, and the solution or dispersion is prepared and the synthetic resin film surface of the support is prepared. Then, the patch of the present invention is obtained by coating and drying. The moisture permeability of the patch is 100 to 100 for the same reason as that of the invention according to claim 1.
It is adjusted to the range of 500 g / m ² · 24 hr.

[0040]

According to the patch of the invention described in claim 1 and claim 2, since the through-holes having a uniform pore diameter can be formed in the support by changing the hole density by laser processing, the patch can be formed. It becomes easy to control the water vapor transmission rate, and by adjusting to give a specific water vapor transmission rate, it is possible to effectively evaporate the water generated by perspiration, improve the absorbability of drugs, and prevent skin damage. Hard to happen. Such a patch is suitably used for treatment or prevention of various diseases by containing various drugs according to the purpose. Also,
The absorption amount can be adjusted by the drug. Also,
The patch of the invention according to claim 2 strengthens the support to prevent the adhesives from sticking to each other during sticking and wrinkles from occurring during sticking.

[0041]

EXAMPLES The present invention will be described below with reference to examples.

(Example 1) Acrylic pressure-sensitive adhesive [Copolymer of methacrylic acid and butyl acrylate (molar ratio 3: 9
7), "Primal N-580" manufactured by Nippon Acrylic Chemical Co., Ltd.
(NF-22) ”], 100 g, indomethacin 2 g, and crotamiton 2 g were uniformly dissolved in 300 g of ethyl acetate to prepare a mixed solution. This compounded solution has a thickness of 5 when dried.
The film was spread on polyethylene-coated glassine paper so as to have a thickness of 0 μm, dried at 60 ° C., and then SIS film porousized by laser processing [“Califlex TR1101” manufactured by Shell Kagaku Co., Ltd. was heated and melted to form a film The thickness of 60 μm) is made porous by laser processing. The porous film has a pore size of 2 to 3 μm, a pore density of 20%, and a water vapor transmission rate of 1400 g / m ² · 24.
It was hr. When the shape of this hole was observed with a microscope, it was found to be a substantially cylindrical through hole. ] Was brought into close contact to obtain a patch. The moisture permeability of the obtained patch was measured according to JIS Z
0208 Moisture Permeability Testing Method for Moisture-Proof Packaging (Cup Method)
300g / m ² · 24hr
Met. With respect to the obtained patch, a human patch test and a drug permeability test using the skin of nude mice were conducted by the following methods, and the results are shown in Table 1.

<Person test for patching> The patch 2 × 2 cm obtained by the above method was stuck on the upper arm of the test subjects (10 healthy males), the sticking property (ease of sticking), the sticking feeling after sticking,
And the degree of skin irritation by the test piece after being applied for 24 hours was tested, and the results are shown in Table 1. 1) In the section of adhesiveness, ◯ indicates that the patch has an appropriate elasticity and can be applied uniformly during application. 2) In the section of feeling of sticking, ○ means that the patch does not feel uncomfortable because it fits on the skin surface, and △ means that the skin feels uncomfortable such as the skin being stretched at the flexion / extension part such as a joint. Are shown respectively. 3) In the section of skin irritation, + indicates that clear erythema was observed, ± indicates that slight erythema was observed, and − indicates that there was no abnormality.

<Nude Mouse Skin Permeability of Drug> The skin extracted from the back of a nude mouse was set in a Franz diffusion cell, and the patch (area: 2 cmφ = 3.14) was placed on this skin.
cm ² ) is attached. A phosphate buffer (pH 7.2) was used as the receptor solution, the amount of indomethacin transferred from the patch to the receptor solution through the skin was measured by HPLC after 24 hours, and the skin permeability of indomecitane was calculated by the following formula. This test was repeated 3 times, and the skin permeability was determined by the average value thereof.

(Comparative Example 1) A SIS film (thickness 150 μm) in which a support was not made porous by laser processing
A patch was obtained in the same manner as in Example 1 except that m) was used. The obtained patch was subjected to a moisture permeability measurement, a human patch test and a drug permeability test using nude mouse skin in the same manner as in Example 1, and the results are shown in Table 1.

(Comparative Example 2) SIS film (thickness 60 μm) in which the support is not made porous by laser processing.
A patch was obtained in the same manner as in Example 1 except that The obtained patch was subjected to a moisture permeability measurement, a human patch test and a drug permeability test using the skin of nude mice in the same manner as in Example 1, and the results are shown in Table 1.
It was shown to.

(Example 2) The SIS film was changed to a polyethylene film (thickness 30 μm), and it was perforated by laser processing (the perforated film had a pore diameter of 30 μm and a pore density of 5%). Non-woven polypropylene (manufactured by Japan Vilene Co., Ltd., basis weight: 70 g / m
^A patch was obtained in the same manner as in Example 1 except that a laminate obtained by thermal fusion bonding of ² ) was used as a support, and the adhesive layer was adhered to the polyethylene film side. The obtained patch was subjected to a moisture permeability measurement, a human patch test and a drug permeability test using nude mouse skin in the same manner as in Example 1, and the results are shown in Table 1.

Comparative Example 3 A patch was obtained in the same manner as in Example 1, except that the polypropylene nonwoven fabric used in Example 2 was used as the support. The obtained patch was subjected to a moisture permeability measurement, a human patch test and a drug permeability test using nude mouse skin in the same manner as in Example 1, and the results are shown in Table 1.

[0049]

[Table 1]

From the comparison between Example 1 and Comparative Example 1 in Table 1,
Since the patch of the present invention is excellent in patchiness and patch feeling and has appropriate moisture permeability, it shows that even when it is patched for a long time, erythema due to irritation does not occur on the skin. On the other hand, the patch using a support which has not been made porous by laser processing has a problem in the feeling of sticking and lacks moisture permeability, and therefore erythema is caused by skin irritation. In Comparative Example 3, a nonwoven fabric is used as the support, but since the moisture permeability is too large, the drug permeability is low. However, by adhering a non-woven fabric to the polyethylene film that has been made porous by laser processing as in Example 2, it is possible to adjust the moisture permeability to an appropriate level, and it is possible to improve the drug utilization rate due to the effect of occlusive bandage therapy. it can.

(Example 3) 100 g of a rubber-based adhesive was added to 15
Melt at 0 ° C, add 3 g of glycol salicylate, 3 g of l-menthol and 20 mg of β-butoxyel nicotinate, mix, and add polyethylene terephthalate (PET) film with silicone treatment to make it releasable.
The thickness of the drug-containing pressure-sensitive adhesive layer is 30μ by the hot melt method.
After being coated so as to have a thickness of m, a polyurethane film (having a thickness of 60 μm) is made porous by laser processing (the pore diameter of the porous film is 0.2 to 0.3 μm,
The pore density was 48%), and the patch was obtained. The moisture permeability of this patch was 240 g / m ² · 24 hr. still,
The rubber-based pressure-sensitive adhesive is 20 parts by weight of a SIS block copolymer (“Califlex TR1107” manufactured by Shell Chemical Co., Ltd.),
Alicyclic saturated hydrocarbon resin (Arakawa Chemical Co., Ltd. "Alcon P-
90 ") 40 parts by weight, liquid paraffin 40 parts by weight and polybutene (" 300H "manufactured by Idemitsu Co., average molecular weight 145).
0) A mixture of 10 parts by weight was used.

<Preservation test> The above patch was cut into a piece of 5 cm x 5 cm to give a test piece, and the test piece was sealed in an aluminum packaging material (manufactured by Fujimori Industry Co., Ltd.) with the release film attached.
After storing at 0 ° C for 2 weeks, the external appearance of the patch was observed, and the test piece was extracted with an organic solvent and then subjected to high performance liquid chromatography to measure the drug content in the drug-containing pressure-sensitive adhesive layer and start storage. The residual rate (%) of the drug after storage with respect to the previous drug content was determined, and the results are shown in Table 2. The aluminum packaging material is PET film (12 μm
Thickness), a low density polyethylene film (13 μm thickness), a soft aluminum (9 μm thickness) and a low density polyethylene film (40 μm thickness).

(Comparative Example 4) A patch was obtained in the same manner as in Example 3 except that a polyurethane film (thickness 60 μm) which was not subjected to laser processing was used as the support.
The moisture permeability of this patch was measured in the same manner as in Example 1, and it was 60 g / m ² · 24 hr. A storage test was conducted on the above-mentioned patch in the same manner as in Example 3, and the results are shown in Table 2.

(Comparative Example 5) A patch was prepared in the same manner as in Example 3 except that a polypropylene resin was melt-cast into a film and then uniaxially stretched to make it porous (thickness: 60 μm). Obtained. The moisture permeability of this patch was measured in the same manner as in Example 1, and it was 390 g / m ² · 2.
It was 4 hours. A storage test was conducted on the above-mentioned patch in the same manner as in Example 3, and the results are shown in Table 2.

[0055]

[Table 2]

In the patch of Comparative Example 5, after the storage test, the pressure-sensitive adhesive was exuded from the back surface of the support and felt sticky. No exudation was found on the other test pieces.
From these results, it is expected that in the film made porous by stretching, it is difficult to control the size of voids, and extremely large voids are opened, and the pressure-sensitive adhesive exudes from there. On the other hand, the film made porous by laser processing is
Since the pore size is small, the adhesive does not seep out. 6
The residual ratio of the drug after storage to the drug content before storage at 0 ° C. for 2 weeks was 95% or more.

[0057]

According to the first and second aspects of the present invention, as described above, by applying the laser processing to the support, a patch having an appropriate moisture permeability can be obtained. Therefore, a drug-containing patch can be obtained in which the drug is effectively absorbed into the skin without causing skin disorders, has excellent adhesiveness, and is well adapted to the skin. Moreover, such a patch is suitably used for treatment or prevention of various diseases by containing various drugs. According to the invention described in claim 2, since the support of the obtained patch has a strong elasticity, the adhesives do not stick to each other and wrinkles do not occur on the support during application.

Claims (2)

[Claims] 1. A patch comprising a synthetic resin film support having a drug-containing pressure-sensitive adhesive layer formed on one surface thereof, the support having a through-hole having a pore size of 0.1 to 60 μm, which has been previously laser-processed. However, a large number of holes are formed to have a pore density of 1 to 50%, and the moisture permeability of the entire patch is 100 to 500 g / m ² · 2.
A patch using a moisture-permeable support, which is characterized in that it is 4 hours. 2. A patch comprising a laminate comprising a synthetic resin film and a non-woven fabric or a woven fabric as a support, and a pressure-sensitive adhesive layer containing a drug formed on the synthetic resin film surface of the support, the support comprising: Has a hole diameter of 0.1-60μ by laser processing beforehand.
A large number of m through holes are provided to have a hole density of 1 to 50%, and the moisture permeability of the entire patch is 100 to 500 g / m ² ·.
An adhesive patch using a moisture-permeable support, which is characterized by being set for 24 hours.