JPH05139960A - Plaster material and plaster preparation - Google Patents

Abstract

PURPOSE:To provide a plaster material useful for plaster preparation, etc., having a tacky adhesive layer composed of a cross-linked polymer on the surface of a substrate, exhibiting an adhesiveness falling within a specific range, smoothly peelable without causing pain and exhibiting the adhesiveness, plastering property and adhesive property over a long period. CONSTITUTION:A tacky adhesive composition composed of 100 pts.wt. of an acrylic polymer, 25-200 pts.wt. of a liquid component compatible with the polymer, e.g. a glycerol ester and 0.05-1.0 pt.wt. of a cross, linking agent is applied in an amount of preferably 8-20g/m<2> to a surface of a substrate such as a polyester film and the coating film is crosslinked to obtain a tacky adhesive layer. The adhesiveness of the tacky adhesive layer is 20-180g/12mm width, preferably 40-150g/12mm width measured by attaching the tacky adhesive faces to each other and peeling at a definite speed at a peeling angle of 180 deg.. A plaster preparation is obtained by incorporating 1-40wt.% of an agent to 100 pts.wt. of the tacky adhesive composition.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a patch and a patch preparation for sticking to a skin surface to protect a wound and absorb a drug through the skin.

[0002]

2. Description of the Related Art Heretofore, in this type of patch and patch preparation, it is known that a polymer alone forms a pressure-sensitive adhesive layer, and the presence of this pressure-sensitive adhesive layer improves the adhesion to the skin. It was possible to fix the patch and patch preparation on the skin.

However, the above patch and patch preparation are
Since it is necessary to securely fix it on the skin surface for a long time, the skin adhesive force is too strong, and when peeling and removing it from the skin surface after use, it causes pain due to physical irritation due to exfoliation of the skin surface, and sometimes In some cases, significant pain occurred. In order to solve this problem, the present applicant has previously made a polymer layer in which an acrylic acid ester-based polymer contains an excess amount of a liquid component compatible with the polymer in excess of a usual amount to crosslink and gel the polymer layer. It has been found that, by virtue of this, it is possible to prevent the above-mentioned decrease in cohesive force, relax and disperse the stress applied to the skin surface at the time of peeling the preparation, and a good balance between skin adhesiveness and skin irritation is filed. See JP-A-3-220120).

[0004]

However, the patch and patch preparation of the invention described above are excellent ones capable of solving the problems of the conventional patch and patch preparation, but do not always exhibit the above effects, Pain and exfoliation of the skin may still occur when peeling off the skin surface after use. It is an object of the present invention to provide a patch and a patch preparation that can solve the above problems, have excellent long-term adhesion to the skin, and can be smoothly peeled without physical skin irritation (pain) at the time of peeling. To do.

[0005]

Means for Solving the Problems As a result of further intensive studies by the present inventors in order to achieve the above object, the skin adhesiveness and skin irritation of the patch and patch preparation are determined to be the crosslinked state of the adhesive layer. They found that they correlate and completed the present invention. That is, the patch according to claim 1 is a patch having a pressure-sensitive adhesive layer made of a crosslinked polymer on one surface of a support, and the pressure-sensitive adhesive layer surfaces are bonded to each other to obtain a 180-degree constant-angle peel strength. When tested, the adhesive strength is 20-180g / 12
It indicates the mm width. Moreover, the patch preparation according to claim 2,
A drug is mixed in the pressure-sensitive adhesive layer.

[0006]

The patch and patch preparation of the present invention form a pressure-sensitive adhesive layer exhibiting a specific adhesive force when the above-mentioned cross-linked pressure-sensitive adhesive layers are pasted together and subjected to a 180-degree angle constant speed peel strength test. Therefore, it has excellent adhesion to the skin for a long period of time, and exhibits suitable adhesion to the skin, good adhesion (adhesion), and physical skin irritation (pain) with no exfoliation of keratinocytes. Does not occur.

Explaining the present invention in more detail, the support used in the patch and patch preparation of the present invention is not particularly limited, but the liquid component or drug contained in the crosslinked adhesive layer is contained in the support. Those which do not pass through the sheet and are lost from the back surface without causing a decrease in content, that is, those in which these pressure-sensitive adhesive layer constituent components are made of an impermeable material are preferable.

Examples of such impermeable supports include polyester, nylon, saran, polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyvinyl chloride, ethylene-ethyl acrylate copolymer, polytetrafluoroethylene, A single film such as Surlyn or a metal foil, or a laminated film thereof may be used.

As this support, one having a thickness that does not impair the soft feeling of the patch and patch preparation, specifically, 1 to 25 μm, preferably 1 to 15 μm, is used.

Further, it is preferable to use a laminate of the above support and a porous film, since the anchoring effect improves the adhesive force between the pressure-sensitive adhesive layer and the support. As the porous film, specifically, paper, woven cloth, non-woven cloth, mechanically perforated sheet, or the like can be used.

The thickness of the porous film is 10 to 500 μm in consideration of the improvement of the anchoring property and the flexibility of the patch and the patch preparation as a whole, and in the case of a thin preparation such as a plaster type or an adhesive tape type. , 10-200
It is preferably in the range of μm.

When a woven fabric or a non-woven fabric is used as the porous film, the basis weight of the pressure-sensitive adhesive layer is 5 to 30 g / m.
² , preferably 8 to 20 g / m ² is preferable because the anchoring property is improved.

Further, in order to control the drug release of the patch preparation, the support can be made relatively breathable.

In the present invention, since a pressure-sensitive adhesive layer made of a crosslinked polymer is formed on one surface of the support of the patch or patch preparation, it has appropriate skin adhesiveness and cohesive force. .. The adhesive force of this adhesive layer surface is obtained by bringing the adhesive layer surfaces of the patch or patch preparation into close contact with each other, applying a load to them, and then bonding the bonded product with a 180 degree angle constant speed peel strength test. Those having an adhesive strength of 20 to 180 g / 12 mm width as measured, preferably 30 to 165 g / 12 mm width, more preferably 40
Those having a width of up to 150 g / 12 mm are suitable.

When a patch or patch preparation having a pressure-sensitive adhesive layer showing the above-mentioned adhesive strength is used, it has excellent adhesiveness and adhesion to the skin, and when it is peeled and removed after application to the skin, keratinocytes on the skin surface It is possible to peel smoothly without causing physical skin irritation (pain) due to peeling. Further, the pressure-sensitive adhesive layer has appropriate cohesiveness due to the cross-linking treatment, and is excellent in sticking property to skin and peeling property (no adhesive remains).

The polymer which is a film-forming component of the pressure-sensitive adhesive layer is not particularly limited, but rubber-based, acrylic-based, silicone-based, and other polymers can be used, and the acrylic-based polymer is particularly preferable. ..

Examples of the acrylic polymer include (meth) acrylic acid alkyl ester polymers having a linear alkyl group or a branched alkyl group. As the (meth) acrylic acid alkyl ester-based polymer,
A polymer obtained by polymerizing a (meth) acrylic acid alkyl ester having an alkyl group with 4 or more carbon atoms, especially because the (meth) acrylic acid alkyl ester is the main component and is copolymerized with other copolymerizable monomers because of ease of crosslinking reaction. Preference is given to using polymerized copolymers.

As the copolymerizable monomer to be copolymerized with the above-mentioned (meth) acrylic acid alkyl ester, a carboxyl group-containing monomer, a sulfoxyl group-containing monomer, a hydroxyl group-containing monomer, an amide-containing monomer, an alkylaminoalkyl group-containing monomer, (meth ) Acrylic acid alkoxyalkyl ester, alkoxy group (or ether bond in the side chain) -containing (meth) acrylic acid ester,
Examples thereof include vinyl-based monomers, and these can be used alone or in combination of two or more kinds for copolymerization.

The above-mentioned copolymerizable monomer is used for adjusting the cohesive force of the pressure-sensitive adhesive layer and for improving the solubility of the drug compounded in the pressure-sensitive adhesive layer. The type and amount of the monomer to be used depend on the purpose. It may be arbitrarily selected.

The liquid component used in the present invention has a property of being compatible with the above-mentioned polymer, and when it is contained in the pressure-sensitive adhesive layer, the pressure-sensitive adhesive layer is plasticized to give a soft feeling, and It has good adhesiveness to the skin and also has a role of reducing pain and skin irritation caused by the skin adhesive force when peeling the crosslinked adhesive layer from the skin surface.

The liquid component may be any one having a plasticizing action, but it is preferable to use one having an absorption promoting action in order to improve the transdermal absorbability of the drug to be coexisted.

The liquid component is not particularly limited as long as it is compatible with the polymer, but glycols, oils and fats, organic solvents, liquid surfactants, plasticizers, hydrocarbons, ethoxylated compounds. Stearyl alcohol, glycerin ester, isopropyl myristate, isotridecyl myristate, ethyl laurate, N-methylpyrrolidone ethyl oleate, oleic acid, diisopropyl adipate, isopropyl palmitate, octyl palmitate, 1,3-butanediol and the like. Be done.

The amount of the above liquid component is 100 parts by weight of the polymer in consideration of the cohesiveness of the pressure-sensitive adhesive layer, the flexibility, the adhesiveness to the skin, the adhesiveness (paste residue), the skin irritation and the like. On the other hand, it is 20 to 200 parts by weight, preferably 40 to 180 parts by weight. If it exceeds 200 parts by weight, cohesive failure occurs in the adhesive layer, and if the patch or patch preparation is peeled from the skin, a significant amount of the adhesive remains on the skin, which is not preferable. On the other hand, if the amount is less than 20 parts by weight, the plasticizing effect cannot be obtained and the adhesion to the skin is deteriorated, which is not preferable.

The above-mentioned pressure-sensitive adhesive layer is formed by directly applying the above-mentioned pressure-sensitive adhesive composition onto a support material by a suitable method, for example, a roll coater, a reverse coater, a doctor blade, a bar or the like.
Alternatively, a dry film thickness of the adhesive is 30 to 1 on the release liner.
After coating so as to have a thickness of 20 μm, this pressure-sensitive adhesive layer is adhered to a support material.

In the present invention, the adhesive layer is subjected to a crosslinking treatment in order to exhibit appropriate adhesiveness to the skin and reduce physical skin irritation (pain) due to exfoliation of keratinocytes when peeling after application. Is an essential requirement.

The cross-linking treatment is carried out by physical cross-linking by irradiation with radiation such as UV irradiation or electron beam irradiation, or chemistry using a cross-linking agent such as polyisocyanate compound, organic peroxide, organic metal salt, metal alcoholate or metal chelate compound. Crosslinking treatment is performed. However, in the patch preparation of the present invention, since the drug is mixed in the adhesive layer, it is necessary to select a crosslinking treatment method that does not decompose or react the drug.

When the pressure-sensitive adhesive layer is cross-linked by the above method, the liquid component contained in the pressure-sensitive adhesive layer can be prevented from flowing out, and the pressure-sensitive adhesive layer can be provided with an appropriate cohesive force as a patch.

The amount of the above-mentioned cross-linking agent added is such that the adhesiveness (sticking) to the skin is good without impairing the flexibility required for the patch or patch preparation, and the physical skin irritation (pain) upon peeling. ) Need to be adjusted.
Specifically, it is 0.05 to 1 with respect to 100 parts by weight of the polymer.
It is preferable to add parts by weight. If it is less than 0.05 parts by weight, the adhesive force on the surface of the pressure-sensitive adhesive layer exceeds 180 g / 12 mm width, and physical skin irritation (pain) is severe when peeling the patch from the skin, which may cause significant damage to the skin. There is. When it exceeds 1 part by weight, the adhesive force on the surface of the pressure-sensitive adhesive layer becomes less than 20 g / 12 mm width, the pressure-sensitive adhesive layer becomes inflexible and lacks adhesiveness to the skin, and can be used as a patch or patch preparation. Disappear.

Even when the polymer of the pressure-sensitive adhesive does not have a functional group capable of reacting with the above-mentioned crosslinking agent, it can be modified into a structure capable of crosslinking treatment by subjecting the substance to be crosslinked to alkali treatment or the like. ..

In the present invention, a medicated patch is prepared by incorporating a drug into the adhesive layer of the medicated patch. The drug to be contained is arbitrarily selected according to the purpose of treatment, for example, corticosteroids, analgesic and anti-inflammatory agents, hypnotics, tranquilizers, antihypertensive agents, antihypertensive diuretics, antibiotics, Percutaneous absorption of anesthetics, antibacterial agents, antifungal agents, vitamins, coronary vasodilators, antihistamines, antitussives, sex hormones, antidepressants, cerebral circulation improvers, antiemetics, antitumor agents, biopharmaceuticals, etc. Those can be used, and if necessary, two or more kinds can be used in combination.

The content of the above-mentioned drug is appropriately set depending on the kind of the drug and the purpose of administration, but is generally 1 to 40% by weight, preferably 3 to 30% by weight of the pressure-sensitive adhesive composition. It is a degree. If the content is less than 1% by weight, the amount of drug absorbed into the body is small and no therapeutic effect is observed.
If it exceeds 40% by weight, the therapeutic effect is limited and it is economically disadvantageous, which is not preferable.

[0032]

EXAMPLES Examples will be shown below for further detailed description. In the following, parts and% mean parts by weight and% by weight. Example 1 An acrylic acid ester-based polymer solution was prepared by copolymerizing 95 parts of 2-ethylhexyl acrylate and 5 parts of acrylic acid in 50 parts of ethyl acetate under an inert gas atmosphere. To 100 parts of the polymer of this solution, 0.14 parts of trifunctional isocyanate (trade name Coronate HL, manufactured by Nippon Polyurethane Industry Co., Ltd.) was added to obtain a viscous solution. This viscous solution was coated on a 75 μm thick polyester release liner with a doctor blade so that the thickness after drying was 60 μm, and dried at 100 ° C. for 5 minutes, and then a polyester nonwoven fabric (12 g / m ² ) A support having a 2 μm polyester film laminated thereon was attached to obtain a patch.

Comparative Example 1 A patch was obtained in the same manner as in Example 1 except that the trifunctional isocyanate was not added and the pressure-sensitive adhesive layer was formed by the acrylic ester polymer solution alone.

Example 2 The same as Example 1 except that 48.2 parts of isopropyl myristate and 0.07 part of trifunctional isocyanate were mixed with 51.8 parts of the polymer of the acrylic ester polymer solution. Then, the patch was obtained.

Comparative Example 2 A patch was obtained in the same manner as in Example 2, except that the pressure-sensitive adhesive layer was formed without adding the trifunctional isocyanate. This patch was markedly cohesively broken and could not be subjected to all the tests described below.

Example 3 In Example 1, 40 parts of isopropyl myristate was added to 43 parts of the polymer of the acrylate polymer solution.
Parts, isosorbitodinitrate 17 parts, and trifunctional isocyanate 0.06 parts were all mixed in the same manner to obtain a patch preparation.

Example 4 A patch preparation was obtained in the same manner as in Example 3, except that 0.06 part of ethyl acetoacetate aluminum diisopropylate was used instead of 0.06 part of the trifunctional isocyanate.

Example 5 In an inert gas atmosphere, 75 parts of 2-ethylhexyl acrylate, 22 parts of N-vinyl-2-pyrrolidone and 3 parts of acrylic acid were copolymerized in 150 parts of ethyl acetate to form an acrylate ester system. A polymer solution was prepared. 0.2 part of a trifunctional isocyanate was added to 100 parts of a polymer of this solution to obtain a viscous solution. Then, the same operation as in Example 1 was performed to obtain a patch.

Example 6 The same as Example 1 except that 40 parts of octyl palmitate and 0.12 parts of trifunctional isocyanate were added to 60 parts of the polymer of the acrylic acid ester-based polymer solution. The operation was performed to obtain a patch.

Comparative Example 3 A patch was obtained in the same manner as in Example 6, except that the compounding amount of the trifunctional isocyanate was changed to 0.6 part.

Comparative Example 4 A patch was obtained in the same manner as in Example 6, except that the compounding amount of the trifunctional isocyanate was changed to 0.03 part.

Example 7 In Example 5, with respect to 57.5 parts of the polymer of the acrylic acid ester-based polymer solution, 4 octyl palmitate was added.
A patch preparation was obtained by the same procedure except that 0 part, 2.5 parts of estradiol and 0.115 part of a trifunctional isocyanate were added.

Experimental Example The samples obtained in Examples 1 to 7 and Comparative Examples 1 to 4 were stored at 70 ° C. for 2 days, and then the following tests were conducted. [Adhesive strength of pressure-sensitive adhesive layer] After cutting each sample into a width of 12 mm and peeling off the liner, the two pressure-sensitive adhesive layer surfaces of each sample are brought into close contact with each other, and then a roller having a load of 850 g is made to reciprocate once to be bonded. It was Then 1 piece of this laminated product
It was peeled off at a speed of 300 mm / min. In the direction of 80 degrees, and the adhesive force was measured. In addition, the said adhesive force was measured using the Shopper tension tester (made by Ueshima Seisakusho).

[Skin patch (adhesion)] Each sample was stuck on the inner side of the upper arm of 6 volunteers, and the skin patch (adhesion) after 24 hours was visually evaluated. The best adhesion (good adhesion) was rated as 5, and the marked peeling was rated as 1.

[Skin irritation (pain) at the time of peeling] After measuring the skin adhesiveness, the degree of skin irritation (pain) at the time of peeling the sample was measured in 5 steps. The average value was calculated by setting 1 as one having no skin irritation. As a reference, Comparative Example 1
Was evaluated as 5.

[0046]

[Table 1]

As is clear from Table 1, the patch and patch preparation of the present invention have good skin patchability and
It has almost no physical irritation (pain) when peeled from the skin.

[0048]

EFFECTS OF THE INVENTION The patch and patch preparation of the present invention are such that when the pressure-sensitive adhesive layers made of the above-mentioned cross-linked polymer are stuck together, the adhesive strength is 20 to 180 g / 12 mm width. As the blending ratio of the components of the layer is adjusted, it has excellent long-term adhesiveness to the skin and adhesiveness (adhesion). Furthermore, physical skin irritation (pain) due to exfoliation of keratinocytes when exfoliating after application is achieved. Does not happen.

Further, the cross-linking treatment allows the pressure-sensitive adhesive layer to have good shape retention and cohesiveness, and the pressure-sensitive adhesive does not remain on the skin during peeling.

Further, the patch preparation containing the drug can release the drug to the skin surface appropriately, and the drug is transdermally administered to the living body through the skin surface to treat or prevent various diseases. It is effective.

Front page continuation (72) Inventor Saburo Otsuka 1-2-2 Shimohozumi, Ibaraki City, Osaka Prefecture Nitto Denko Corporation (72) Inventor Takamitsu Muraoka 1-21-2 Shimohozumi, Ibaraki City, Osaka Nitto Denko Stock In the company

Claims (4)

[Claims] 1. A patch having a pressure-sensitive adhesive layer made of a cross-linked polymer on one surface of a support, wherein the pressure-sensitive adhesive layer surfaces are bonded to each other and subjected to a 180-degree constant-angle peel strength test. An adhesive material having an adhesive strength of 20 to 180 g / 12 mm width. 2. A pressure-sensitive adhesive layer, wherein the pressure-sensitive adhesive layer is composed of 25 to 200 parts by weight of a liquid component compatible with the polymer and 100 to 100 parts by weight of the polymer, and 0.05 to 1.0 parts by weight of a crosslinking agent. The patch according to claim 1, wherein the composition is formed into a film and crosslinked. 3. A patch preparation in which a drug is contained in the pressure-sensitive adhesive layer according to claim 1. 4. The adhesive preparation according to claim 3, wherein the drug is contained in the range of 1 to 40% by weight based on 100 parts by weight of the pressure-sensitive adhesive composition.