JPS59164714A - Remedial adhesive tape or sheet - Google Patents

Abstract

PURPOSE:The titled tape, containing a specific chemical and an organic acid salt or inorganic acid salt of Mg, Ca, Zn or Al in a pressure-sensitive adhesive layer provided on a base material, capable of dissolving a large amount of the chemical therein without deterioration thereof, and having stable dissolution state with time. CONSTITUTION:A remedial adhesive tape containing a hydrophilic chemical, e.g. a nonsteroid anti-inflammatory agent such as ''Indomethacin'' or ''Diclofenac'', having carboxyl groups or alkali metal salts thereof in the molecule thereof, and slightly soluble or insoluble in an ester (1g or less amount of dissolved chemical in 100g ester such as ethyl acetate at 20 deg.C and 10-100wt%, based on the amount of the chemical, organic acid or inorganic acid salt of a metal selected from Mg, Ca, Zn or Al, in a pressure-sensitive adhesive layer, preferably a pressure-sensitive adhesive layer containing an alkyl acrylate or methacrylate as a polymerization component, provided in a base material. EFFECT:A high chemical effect can be obtained since a large amount of the chemical can be contained.

Description

[Detailed description of the invention] The present invention relates to therapeutic adhesive tapes or sheets.

A therapeutic adhesive tape or sheet, which has a thin layer of a pressure-sensitive adhesive layer mixed with a therapeutic agent on a base material, is applied to the skin of the adherend, and the adhesive oozes out from the pressure-sensitive adhesive layer. Treatment is often carried out with drugs.

As a therapeutic adhesive tape or a sheet, a therapeutic agent with good solubility is added to a pressure-sensitive adhesive layer containing acrylic acid ester or #-i (and) methacrylic acid ester as a polymerization component. things are used.

However, as a drug, non-steroidal anti-inflammatory drugs such as indomethacin, dichloro-7enac sodium, and amfenac natrichum have a carboxyl group or an alkali metal salt thereof in the molecule, and are hydrophilic and ester. When a drug is used that is insoluble or poorly soluble, it may be difficult to dissolve in the pressure-sensitive adhesive, or the compatibility may be unstable, making it difficult to formulate it into a tape, sheet, etc. There were drawbacks.

This is hydrophilic and insoluble in esters.
< i. - A soluble drug means a drug that is woody and dissolves well in water, methanol, etc., but is substantially insoluble in esters such as ethyl acetate. do.

Also, ``dissolution'' refers to the mixing of the drug with the pressure-sensitive adhesive to form a homogeneous state, and compatibility refers to the property that the drug and the pressure-sensitive adhesive dissolve into each other.

In order to increase the solubility of the drug, the composition of the pressure-sensitive adhesive can be modified to increase its hydrophilicity by increasing the amount of polar components such as methacrylic acid, acrylonitrile, butoxyethyl (meth)acrylate, etc. However, in this case, the pressure-sensitive adhesive loses its tackiness, and has the disadvantage of causing other problems such as increased toxicity and skin irritation.

The present invention solves the drawbacks of the conventional pressure-sensitive adhesive tapes or sheets, and uses drugs such as indomethacin, diclo-7enac sodium, amfenac sodium, etc., which have a carboxyl group or an alkali metal group in the molecule.
1 salt and is hydrophilic and is insoluble or poorly soluble in esters, it exhibits a stable compatibility state in pressure-sensitive adhesives and maintains a high level of compatibility over a long period of time. The purpose of the present invention is to provide a therapeutic adhesive tape or sheet that can exhibit medicinal efficacy.

The gist of the present invention is that a pressure-sensitive adhesive layer is provided on a base material,
The l & pressure bonding adhesive layer has a carboxyl group or an alkali metal salt thereof in one molecule, and a drug that is wood-philic and 11 bud-like or insoluble in esters, and an organic or inorganic acid such as magnesium, calcium, The therapeutic adhesive tape also consists in a sheet, characterized in that a salt of a metal selected from aluminum is present.

Next, I will further explain about the therapeutic adhesive tape and sheet of the present invention.

The base material used in the present invention is preferably made of a flexible material such as polyethylene, polypropylene, ethylene-vinyl acetate copolymer, soft polyvinyl chloride, cellophane, or the like. The thickness of the base material is preferably in the range of a02 to (115 sm).

The base material is subjected to corona discharge treatment, plasma treatment, primer coating, etc., if necessary, in order to increase the adhesion with the pressure-sensitive adhesive layer.

A pressure adhesive layer is formed on the base material. Examples of pressure-sensitive adhesives include synthetic resin-based adhesives, synthetic Go5-based adhesives,
Natural rubber systems, natural rubber-synthetic rubber mixture systems, etc. are used, but particularly preferred are polymers or copolymers of alkyl acrylates, polymers or copolymers of alkyl methacrylates, and acrylic acid alkyl esters. It is a copolymer system of alkyl ester and methacrylic acid alkyl ester.

In addition, examples of ester residues in acrylic acid alkyl esters and methacrylic acid alkyl esters as polymerization components include methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, n-pentyl group, isoben 5 - thyl group, 2-methylbutyl group, n-hexyl group, 2-methylpentyl group, 3-methylpentyl group, "2-ethylbutyl group, n-octyl group, inoctyl group, 2-ethylhexyl group, nonyl group, n -f sil group, lacryl group, etc.

Particularly preferred acrylic acid alkyl esters include ethyl acrylate, n-butyl acrylate, inbutyl acrylate, isoamyl acrylate, 2-ethylhexyl acrylate, n-octyl acrylate, lacryl acrylate, and methacrylic acid. Examples of the ester include methyl methacrylate, butyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, and lacryl methacrylate.

Examples of other polymerizable monomers and bodies that can be copolymerized with acrylic acid alkyl esters and methacrylic acid alkyl esters include vinyl esters such as vinyl acetate; styrene, α
-Methylstyrene, a91Ju nitrile, vinyl j41; ethylene, α-olefins such as pro6-pyrene; diene monomers such as butadiene and isoprene, diacetone acrylamide, polypropylene glycol monoacrylate or polypropylene glycol methacrylate Shun ester etc.

The copolymerization content of the monomers in such polymerization examples is preferably in the range of 0.1 mol% to 30 mol%, and a1 mol%
If the amount is less than 30% by mole, the drug will not be compatible, and if it is more than 30% by mole, the water resistance of the polymer will decrease and the adhesion to the substrate will decrease.

The pressure-sensitive adhesives containing acrylic acid alkyl esters and methacrylic acid alkyl esters as polymerization components as described above are suitable because they are resistant to deterioration and deterioration, and have little toxicity and irritation to the skin. This is due to its excellent adhesion to the skin and excellent drug solubility.

However, in the invention, the compatibility between the pressure-sensitive adhesive and the drug and the compatibility of the drug can be achieved by using a metal salt of an organic acid or an inorganic acid, which will be described later. Those containing no ester or alkyl methacrylate as a polymerization component can be used.

The pressure-sensitive adhesive layer contains a drug that has a carboxyl group or an alkali metal salt thereof in its molecule, is hydrophilic, and is sparingly soluble or insoluble in esters. The degree of poor solubility or insolubility specifically refers to the amount dissolved in 100p of an ester such as ethyl acetate at 20°C of 15F or less.

As the alkali metal salt, a sodium salt or a potassium salt is suitable.

In order to exhibit medicinal efficacy, such a drug is required to be contained in an extremely large amount in the adhesive layer on the pressure contact side, that is, several times to several tens of times the amount of a normal drug.

In addition, if a normally used amount of Ktf is added to the pressure-sensitive adhesive layer as it is, good medicinal effects cannot be obtained.On the other hand, if a large amount of Ktf is added, it is not well dissolved in the pressure-sensitive adhesive. .

Representative examples of such drugs include non-steroid F-based anti-inflammatory drugs, such as indomethacin, acemethacin, sulindac, diclonac sodium (or carithum), 7-ene, tolmetin, mefenamic acid, and turmeric. 7 enamic acid, flufenamic acid sodium, aspirin or its derivatives, ibuprofen, naproquilon,
Ketopro7ene, fenoprofen, fenoprofen, etc. are al.

Even if it is attempted to mix the above-mentioned drug as it is with the pressure-sensitive adhesive, the solubility of the drug is not good. Furthermore, it is necessary to dissolve a large amount of a drug in order to obtain a medicinal effect.17 In order to dissolve a large amount of a drug, K must make the pressure-sensitive adhesive hydrophilic.

As the hydrophilicity of the pressure-sensitive adhesive increases, its adhesive performance decreases;
The skin irritation increases, and if the drug is not sufficiently dissolved, it tends to cause splitting, precipitation, crystallization, etc. of the drug due to changes over time, accelerated aging, etc.

9- Therefore, in the present invention, a salt of a metal selected from organic or inorganic acids such as magnesium, calcium, zinc, or aluminum is present in the pressure-sensitive adhesive layer together with the above-mentioned drug.

It has become clear that when the metal salt of an organic or inorganic acid is used, a large amount of the drug is dissolved in the pressure-sensitive adhesive without deterioration, and the dissolved state becomes stable over time. The reason for this effect is presumed to be that a weak ionic bond is formed between the carboxyl group or carboxylic acid base in the drug and the metal salt of the coexisting organic or inorganic acid. be done.

Examples of the metal salts of organic acids or inorganic acids include magnesium acetate, magnesium chloride, magnesium nitrate, lucium acetate, lucium chloride, lucium nitrate, zinc acetate, zinc chloride, zinc sulfate, aluminum chloride, aluminum sulfate, etc. be. The amount of these metal salts to be used is preferably 5 to 300% by weight, and most preferably 10 to 100% by weight based on the pharmaceutical cost.

-１〇- And the pressure adhesive is acrylic acid alkyl ester,
In the case of a copolymer of methacrylic acid alkyl ester and diacetone acrylamide, polypropylene glycol monoacrylate, polypropylene glycol methacrylate, etc., the pressure-sensitive adhesive will have high hydrophilicity, so Even if the amount of the metal salt of an inorganic acid is reduced, the solubility of the drug can be increased.

According to the therapeutic adhesive tape and sheet of the present invention, a large amount of drug can be contained in the pressure-sensitive adhesive, thereby achieving high drug efficacy, stabilizing the compatibility of the drug, and preventing separation and precipitation. The medicinal effect can be maintained over the flowering period.

Example 1 2-ethylhexyl methacrylate 79,29 (0.4 mol) Butyl acrylate 204.8y (16 mol) 1.6-hexane gelicol dimethacrylate Q51y
(0,0 (102 mol)) The above components were dissolved in ethyl acetate and charged into a reaction vessel as a 70 wt% solution, and under a nitrogen stream while stirring [
The reaction was carried out at 70°C for 20 hours. During this time, 143 f (0,008 mol) of azobisisobutynitrile (0,008 mol) was added in five portions, and for the viscosity -1, a concentration reduction method was used by adding ethyl acetate. The adhesive solution thus obtained has a 24-fold vertical non-volatile content. was.

Indomethacin zs y and magnesium acetate tetrahydrate tOy were added to the adhesive solution 509 thus obtained. In this case, indomethacin is a 10% by weight solution of methyl ethyl ketone to methanol (1:1), and magnesium acetate tetrahydrate is 5% by weight in methanol.
Mixed as a solution.

The above mixed solution was applied onto silicone release paper using a knife adjusted to a thickness of 40 μm after drying, dried, and then one side of polyethylene was treated with corona discharge to improve its adhesion properties. lI of terephthalate film (thickness 20 μm)! Lay them on top of each other on the surface and press them together.
A therapeutic adhesive sheet was obtained.

Next, this therapeutic adhesive sheet was tested for drug compatibility, adhesive strength, and drug release properties in the following manner.

Drug compatibility: The degree of compatibility is divided into the following four levels by visual inspection.

A: No drug precipitation observed.

B: The drug is deposited in sparse dots.

C: The drug is deposited in dots at a fairly high density.

D: The drug is completely deposited.

In accordance with Adhesive Crab J I 5-Z-1522, it was cut into a 15-inch tape, folded back at 180°, and measured as the peeling force.

Drug release properties: A sample was punched into a 60 mm diameter circle, the release paper was peeled off, and the sample was immersed in 50% methanol. It was measured and determined by a comparative quantitative method, and expressed as λd relative to the total content.

The measurement results of the above drug compatibility, adhesive strength, and drug release properties are shown in the Example 10 column of Table 1.

Examples 2 to 4 In Example 1, magnesium acetate tetrahydrate LOy
Instead, magnesium chloride hexahydrate LOy (Example 2), calcium nitrate tetrahydrate 10 (Example 3),
Acetic acid 111! Using lead o, sy (Example 4) 1.
A therapeutic adhesive sheet was prepared in the same manner as in Example 1 except for the above, and then the same performance test as in Example 1 was conducted. The results are shown in the columns of Examples 2 to 4 in Table 1.

Comparative Example 1 In Example 1, a therapeutic adhesive sheet was prepared without using magnesium acetate tetrahydrate.1. , then Example 1
A similar performance test was conducted.

The results are shown in mK of Comparative Example 1 in Table 1.

=14- Example 2 Lacryl methacrylate 127M (15 mol) 2-
Ethylhexyl acrylate 55,2 f (0.3 mol) n-butyl acrylate 14al' (11 mol) diacetone acrylamide F 16. 'l' (0,1 mol) polyethylene glycol diacrylate 0.093
y (0,0003 mol) One minute of the above solution was dissolved in ethyl ff acid, and a 70% by weight solution was charged into a reaction vessel, and the reaction was carried out at 65° C. under a nitrogen stream for 20 hours with stirring. During this time, Lafuroyl peroxide 2.4F (0,003 mol) was added in 5 portions, and the concentration was gradually reduced by adding ethyl acetate to prevent an increase in viscosity. The adhesive solution thus obtained was 26
It had a non-volatile content of % by weight.

Diclofenac natrichum L3y and magnesium chloride hexahydrate Q,8y were added to 50y of the adhesive solution thus obtained.

In this case, diclofenac sodium and magnesium chloride hexahydrate were both mixed as 5% by weight methanol solutions.

A therapeutic adhesive sheet was obtained in the same manner as in Example 1 using the above mixed solution.

Next, this therapeutic adhesive sheet was tested for drug compatibility, adhesive strength, and drug release properties in the following manner.

Drug compatibility: The degree of compatibility is divided into the following four levels by visual inspection.

A: No drug precipitation observed.

B: Drug crystals are precipitated in small patches.

C: Drug crystals precipitate at a fairly high density.

D=Drug crystals precipitate over the entire surface.

sticky crab Same as Example 1.

Drug release properties: Water-methanol mixture as extraction solvent (mixing volume ratio, water:
Using methanol = 95:5), extract the
℃ for 24 hours. Further, the extracted drug IT was measured by a comparative quantitative method using wave body chromatography, and expressed as a percentage of the total content.

The measurement results of the drug compatibility, adhesive strength, and drug release properties are shown in the Example 5 column of Table 2.

Examples 6 to 8 In Example 5, magnesium chloride hexahydrate 0.8
Treatment was carried out in the same manner as in Example 5, except that lucium chloride dihydrate α82 (Example 6), zinc acetate (L5y (Example 7), and aluminum sulfate (Example 8) were used instead). An adhesive sheet for use was prepared, and then a performance test similar to that in Example 5 was conducted.The results are shown in Examples 6 to 8 in Table 2.
Shown in the column.

Comparative Example 2 In Example 5, a therapeutic adhesive sheet was prepared without using magnesium chloride hexahydrate, and then the same performance test as in Example 5 was conducted.

The results are shown in the Comparative Example 2 column of Table 2.

17- Table 1 18- Table 2 patent applicant Sekisui Chemical Co., Ltd. Representative: Mototoshi Fujinuma 19- 122-

Claims (1)

[Scope of Claims] L A base material is provided with a pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer has a carboxyl group or an alkali metal salt thereof in the molecule and is hydrophilic and ester-resistant. A therapeutic adhesive tape or sheet 'L' characterized in that a poorly soluble or insoluble drug and a salt of an organic or inorganic acid of a metal selected from magnesium, calcium, zinc, or aluminum are present. Therapeutic adhesive tape and sheet turtle according to claim 1, characterized in that the polymerization component is a WB pressure bonding adhesive, an acrylic acid alkyl ester or a methacrylic acid alkyl ester.The drug is a non-steroidal anti-inflammatory agent. Claim 1, which is characterized by:
Therapeutic adhesive tape and sheet as described in item 2