JP2512564B2 - Patch - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a patch in which a large amount of a drug is dissolved and a pressure-sensitive adhesive layer having a high drug release property is provided. The pressure-sensitive adhesive layer of this patch has excellent sticking properties to the skin, and has a good balance between tackiness and cohesiveness.

(Prior Art) Patches that are applied to the skin by utilizing the adhesiveness of an adhesive containing a drug and exhibit the medicinal properties of the drug have been proposed in many cases. This type of patch is generally composed of a backing support layer and a pressure-sensitive adhesive layer containing a pressure-sensitive adhesive and a drug. The drug exists in the adhesive layer in a dissolved state, a dispersed state, a microencapsulated dispersed state, a state sealed in a partition container, and the like. Examples of such patches include:
Patch for skin disease treatment comprising an adhesive layer containing an anti-inflammatory corticosteroid and a specific acrylic copolymer and a substrate (Japanese Patent Publication No. 52-18813, Teijin Ltd.), anti-inflammatory steroid and acrylic With a pressure-sensitive adhesive material containing a copolymer formed on an impermeable support film (Japanese Examined Patent Publication No. Sho 52-31405, Eli Lilly), a backing member and a pressure-sensitive adhesive layer. In addition, a medicine bandage further provided with a drug storage layer (Japanese Patent Publication No. 54-16566, Stephen David Goldby), a drug-containing patch layer mainly composed of a specific acrylate copolymer and a carrier And a pharmaceutical member comprising
No. 412, Nitto Denko Co., Ltd.), and a pharmaceutical preparation formed by forming a base material containing a polymer having a glass transition temperature (Tg) of −70 ° C. to −10 ° C. and propatil nitrate on a support (Japanese Patent Application Laid-Open No. S60-187242) 57
No. 183714, Nitto Denko Corporation).

However, the physical properties of the pressure-sensitive adhesive used in these adhesives can be measured using other normal pressure-sensitive adhesive tapes (eg, general stationery tapes, packaging tapes, plastic tapes such as insulating vinyl, and industrial tapes). It is no different from the adhesive that is used. For example, the glass transition temperature (Tg) of this type of adhesive is in the range of approximately -70 ° C to -15 ° C. It is considered that a pressure-sensitive adhesive having a glass transition temperature (Tg) outside this range cannot be put to practical use in terms of tackiness and retention. However, pressure-sensitive adhesives having a Tg in this range cannot generally contain a sufficient amount of drug because of poor compatibility with the drug. Even if an attempt is made to include a large amount of the drug in the adhesive, the adhesive cannot sufficiently dissolve the drug. Even a small amount of dissolved drug is less likely to migrate and diffuse into the adhesive.
Therefore, the drug release of the pressure-sensitive adhesive layer is low, and the rate at which the drug reaches the skin surface and is absorbed by the skin is small. Therefore, even when a patch having such an adhesive layer is applied to the skin,
Sufficient efficacy cannot be obtained.

(Problems to be Solved by the Invention) The present invention is to solve the above-mentioned conventional problems, and an object of the present invention is to provide a patch having a pressure-sensitive adhesive layer in which a large amount of drug is dissolved and the drug is highly released. Is to provide.
Another object of the present invention is to provide a patch which has good adhesion to the skin and has excellent adhesion. Still another object of the present invention is to provide a patch having a good balance between tackiness and cohesiveness.

(Means for Solving the Problems) The present invention uses an adhesive having a glass transition temperature (Tg) of -71 ° C. or lower, which has not been used before.
Since the compatibility between the adhesive and the drug is remarkably improved, a large amount of the drug can be dissolved in the adhesive layer; the drug dissolved in the adhesive layer has high release property because it easily migrates and diffuses; The adhesive layer has good compatibility with the skin and is excellent in adhesiveness and adhesiveness (for example, even if the skin stretches and spreads, the patch does not easily slip); and this adhesive is filled with reinforcing fiber. The drawbacks of using an adhesive having a low Tg are improved by adding the agent, and the balance between the adhesiveness and cohesiveness of the adhesive layer is maintained;

The patch of the present invention is a patch having a backing support layer and an adhesive layer, wherein the adhesive layer has a glass transition temperature (T
g) an adhesive having a temperature of −71 ° C. or lower, a reinforcing fibrous filler,
And a drug, and the pressure-sensitive adhesive is mainly composed of a (meth) acrylic acid ester polymer, and the coercive force value (H) and the cohesive force value (F) of the pressure-sensitive adhesive layer are expressed by the following formulas a and b. Which satisfies the above-mentioned object.

H / F> 0.3 (sec / g) ... a F> 200 (g) ... b In the patch of the present invention, the glass transition temperature (Tg) is −
By using the adhesive at 71 ° C. or less, a large amount of drug can be dissolved in the adhesive. The drug dissolved in the adhesive has a high release property because it easily migrates and diffuses. This is Tg
It is considered that in a low-adhesive adhesive, drug molecules can move freely and actively. The pressure-sensitive adhesive layer containing such a low Tg pressure-sensitive adhesive has excellent adhesiveness to the skin. This is because the polymer molecule that mainly constitutes this adhesive is
It is presumed that this is because it becomes easy to move in segment units. Further, since the cohesive force of the pressure-sensitive adhesive decreases with a decrease in Tg, a reinforcing fibrous filler is contained in this pressure-sensitive adhesive layer in order to maintain the cohesive force. As a result, various defects (for example, exudation, slippage, stringing, and sticking of the adhesive on the skin) that occur in the adhesive layer due to the decrease in cohesive force are improved. As a result, a patch having an adhesive layer in which the balance between adhesiveness and cohesiveness is maintained can be obtained. In addition, adhesive,
By selecting the composition and the content of the reinforcing fibrous filler and the drug, a patch having various different physical properties depending on the purpose is provided.

In order to obtain a pressure-sensitive adhesive having a glass transition temperature (Tg) of −71 ° C. or lower, it is conceivable to use the above alkyl (meth) acrylate polymer having a Tg of −71 ° C. or lower. However, in practice, by adding a softening agent having a Tg lowering effect (Tg lowering agent) or the like to the above (meth) acrylic acid alkyl ester polymer having a Tg of more than -71 ° C, the Tg becomes −
It is prepared as an adhesive of 71 ℃ or less. In order to maintain the physical properties of the obtained pressure-sensitive adhesive, in order to reduce the addition amount of this Tg lowering agent, even if Tg is -71 ° C or more, it is close to -71 ° C (meta).
An alkyl acrylate polymer is used. The Tg specified in the present invention is measured by the DSC method based on JIS K-7121-1987.

The pressure-sensitive adhesive used in the patch of the present invention is mainly composed of an acrylic acid ester polymer, a methacrylic acid ester polymer, a copolymer of acrylic acid ester and methacrylic acid ester, and a mixture thereof.
Since these acrylic polymers are excellent in hypoallergenic or non-irritant properties, adhesion to skin, deterioration resistance, compatibility with many drugs, and ease of molding, they are widely used as adhesives for patches. Has been. Acrylic ester polymers have a lower Tg than methacrylic acid ester polymers,
preferable. However, methacrylic acid ester polymers can also be used.

The acrylic ester polymer to be used is, as an ester residue, an ester having a linear alkyl group having 4 to 9 carbon atoms and a non-tertiary branched chain alkyl group having 6 to 9 carbon atoms. It is formed from an ester or the like. These alkyl groups include n-butyl group, n-hexyl group, n-heptyl group, n-octyl group, n-nonyl group, isooctyl group, 2-ethylhexyl group and the like. Examples of the methacrylic acid ester polymer include an ester having an n-decyl group or an n-dodecyl group as an ester residue. As the methacrylic acid alkyl ester, an ester having a linear alkyl group having 10 to 12 carbon atoms is preferable. These alkyl acrylates and alkyl methacrylates desirably constitute at least 70% by weight of the entire polymer. In addition, the Tg of the polymer composed only of this acrylic acid alkyl ester and methacrylic acid alkyl ester
Is preferably at least −50 ° C. or lower.

It is added to adjust the Tg of the adhesive below -71 ° C
As the Tg lowering agent, a softening agent (or resinous tackifier) compatible with the (meth) acrylic acid ester polymer, a liquid plasticizer, or the like is used. Examples of the Tg lowering agent include phthalate ester plasticizers such as dibutyl phthalate and dioctyl phthalate; sebacate ester plasticizers such as dibutyl sebacate; adipate ester plasticizers such as dioctyl adipate; tributyl. Phosphate plasticizers such as phosphates;
Naturally derived glycerin triester plasticizers such as castor oil; vegetable oils such as olive oil; citrate ester plasticizers such as triethyl citrate; liquid plasticizers such as liquid polyethers; ester gums Examples include rosin ester-based derivatives (resinous tackifiers); compounds such as isopropyl myristate and Azone, which have a drug transfer promoting effect. These Tg lowering agents are usually the above-mentioned (meth) acrylic acid ester polymers 10
It is added in an amount of 50 parts by weight or less per 0 parts by weight. If the addition amount of this Tg lowering agent is too large, the obtained pressure-sensitive adhesive layer becomes too soft and sufficient cohesiveness cannot be obtained.

The reinforcing fibrous filler is an organic and / or inorganic staple fiber. The filler preferably has an average diameter of 100 μm or less and an average fiber length of 25 mm or less (desirably 1 mm or more). The filler is contained in the pressure-sensitive adhesive layer in a proportion of preferably 5 to 60% by weight.
If it is less than 5% by weight, the effect of adding the filler cannot be sufficiently obtained. When it exceeds 60% by weight, the tackiness of the obtained pressure-sensitive adhesive layer decreases. Examples of the inorganic filler include glass fiber, asbestos fiber, carbon fiber and the like. Examples of the organic filler include natural or synthetic cellulose, polyvinyl chloride, polyester, polyacrylonitrile, polyamide (for example, nylon), polyvinyl acetal, polyethylene, polypropylene and the like. It is preferable that two or more kinds of these organic and / or inorganic fillers are mixed and used in order to obtain a high addition effect. If necessary, the surface of the filler is chemically treated (mainly coating) in order to improve the affinity with the adhesive. For example, when the filler is glass fiber, its surface is subjected to borane treatment or the like.

Drugs added to the patch of the present invention include, for example, analgesic and anti-inflammatory agents, steroid hormones, antiallergic agents, antihistamines, coronary vasodilators, calcium antagonists, antibacterial agents, antibiotics, antidotes and antitussives. , Antipruritic, hypnotic,
Psychoactive agents, tranquilizers, blood pressure regulators, diuretics, asthma agents, antiepileptic agents, hormone secretagogues, antiulcer agents,
Examples include stone dissolving agents, carcinostatic agents, vitamin agents, blood circulation promoters, anesthetics, and the like.

Although the pressure-sensitive adhesive of the patch of the present invention is mainly composed of an acrylic acid ester polymer, a methacrylic acid ester polymer, a copolymer of an acrylic acid ester and a methacrylic acid ester, and a mixture thereof, they are within the skeleton of these polymers. Thus, one or more of the following monofunctional monomer units may be copolymerized in a small amount (for example, 30% or less): acrylic acid, methacrylic acid, an ester residue is an alkoxy group or a terminal. (Meth) acrylic acid esters having a polyoxyalkylene group which is an alkyl group, alkylated acrylamide, alkylated methacrylamide, alkoxyalkyl (meth) acrylamide, aliphatic vinyl esters such as vinyl acetate, crotonic acid, vinylpyrrolidone, alkyl Vinyl ether, (meth) ac Ronitoriru, maleic acid anhydride,
Fumaric acid or its ester, diacetone acrylamide, methyl vinyl ketone. Polyfunctional monomers such as the following may also be added at 0.5% or less in order to enable the polymer to be finely crosslinked: hexanediol diacrylate, polyalkylene glycol dimethacrylate, glycerine triacrylate. These monomers have a glass transition temperature, mechanical strength,
It is added for fine adjustment of flexibility, hydrophilicity, affinity with drugs, adhesiveness, polymerizability with essential monomers, and the like.

In the adhesive layer of the patch of the present invention, if necessary, an antioxidant, an antioxidant, a tackiness improver, a drug absorption promoter,
Stabilizers, surfactants, dyes or pigments and the like may be added. Anti-aging agents and stabilizers are used in appropriate amounts for the purpose of preventing and stabilizing the adhesives, drugs and additives. Since the pressure-sensitive adhesive used in the present invention has an excellent drug transfer effect and absorption effect because the Tg is -71 ° C or less, a drug transfer and absorption promoter is added to further enhance these effects. In order to promote the wetting of the skin by the drug, a surfactant is used in an appropriate amount. Further, although the pressure-sensitive adhesive layer is mainly composed of a (meth) acrylic acid alkyl ester polymer, in order to adjust its physical properties, the polymer is mixed with another polymer (for example, rubber) in an amount of about 30% or less of the total polymer component. Component) may be added.

The support of the backing support layer includes any material conventionally known and used. In particular, a plastic film or a sponge sheet having flexibility and extensibility, a flexible woven fabric, a knitted fabric, a non-woven fabric, or a laminated body thereof is preferable. For example, the material of the support is polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer (EV
A), polyethylene (especially low density polyethylene), polybutadiene, styrene-butadiene or styrene-
Of isoprene-based block copolymer resin, butadiene-styrene-methyl methacrylate (MMA) copolymer resin, nylon, polyurethane, alkoxyalkyl (meth) acrylate copolymer, polyvinyl acetal, plasticized cellulose acetate and ethyl cellulose Such fibrin derivatives, polyamino acids, water-insolubilized water-soluble polymers (eg pullulan, polyvinylpyrrolidone) and the like are used. The thickness of the support is 30 to 30 for film.
0 μm, 0.3 for sponge sheets, woven fabrics, knitted fabrics, and non-woven fabrics
~ 3mm.

The patch of the present invention is mainly provided with a backing support layer and a pressure-sensitive adhesive layer, and is provided with a peelable protective paper or sheet attached to the surface of the pressure-sensitive adhesive layer. The releasable protective paper or sheet is sterilized.

There are, for example, the following two methods for obtaining the patch of the present invention.

(I) A pressure-sensitive adhesive solution (or liquid pressure-sensitive adhesive) is applied onto the backing support and dried to form a pressure-sensitive adhesive layer. In this case, the pressure-sensitive adhesive layer may or may not contain a drug. In that case, a drug solution is sprayed or applied to this adhesive layer. After drying the pressure-sensitive adhesive layer again, a peelable protective paper is attached to the surface of the pressure-sensitive adhesive layer, cut and packaged, and then used. However, when the drug is contained in the pressure-sensitive adhesive solution in advance, the steps of spraying or applying the drug solution and drying the pressure-sensitive adhesive layer are not necessary.

(Ii) Releasability A pressure-sensitive adhesive solution (or liquid pressure-sensitive adhesive) is applied on the releasable surface of the protective paper and dried to form a pressure-sensitive adhesive layer. The drug solution is sprayed or applied to this adhesive layer. After drying the pressure-sensitive adhesive layer again, a backing support is laminated on the surface of the pressure-sensitive adhesive layer and pressure-bonded, and cut and packaged for use. However, when the drug is contained in the pressure-sensitive adhesive solution in advance, the steps of spraying or applying the drug solution and drying the pressure-sensitive adhesive layer are not necessary.

In the thus obtained patch of the present invention, the coercive force value (H) and the cohesive force value (F) of the pressure-sensitive adhesive layer containing the pressure-sensitive adhesive, the reinforcing fibrous filler and the drug are as described above. , H / F> 0.3 (sec / g) ... a F> 200g ... b where equation a is that cohesive failure does not occur in the adhesive layer, and Formula b shows that the pressure-sensitive adhesive layer has sufficient adhesive force. The coercive force value (H) and the cohesive force value (F) of the adhesive layer are measured as follows: (a) Coercive force value (H) JIS-Z except that the following conditions were used. The holding force value (H) of the pressure-sensitive adhesive layer was tested according to −0237 (holding force).

Sample size: width 25 ± 0.5mm Attached area of sample to test plate: 25mm × 25mm Hanging load: 1000g Temperature during test: 30 ± 1 ℃ (heating) Measured value: sample after applying load "Slip" is attached part of
Time until the load comes off (in seconds)
Is the holding force value (H). However, the measurement is 18000 seconds (5
Hours).

(B) Adhesive force value (F) The adhesive force value (F) of the adhesive layer was tested according to JIS-Z-0237 (180 degree peeling method adhesive force) except that the following conditions were used.

Sample size: width 25 ± 0.5 mm Temperature during test: 23 ± 2 ° C (room temperature) Measured value: Expressed in g (gram) of the load to be peeled off.

The holding force value (H) and the adhesive force value (F) serve as a reference for the cohesive force and the adhesive force of the adhesive layer, respectively. For example, if the holding power value (H) is low, the pressure-sensitive adhesive layer is liable to cause cohesive failure, and if the adhesive force value (F) is low, the pressure-sensitive adhesive has a necessary and sufficient adhesive force for application to the skin. No longer. However, since the cohesive force and the adhesive force are correlated with each other, the cohesive force value (H) and the adhesive force value (F) of the adhesive layer are
Is not always suitable for practical use. For example, even if the holding power value (H) of the pressure-sensitive adhesive layer shows a high value, if it has a higher pressure value (F), the pressure-sensitive adhesive causes cohesive failure. Conversely, even if the holding force value (H) of the pressure-sensitive adhesive layer is low, if the pressure-sensitive adhesive value (F) is similarly low, the pressure-sensitive adhesive does not cause cohesive failure. Because of this, in order for the pressure-sensitive adhesive layer to have a certain adhesive strength,
The above condition b was set, and the above condition a was set so as to maintain the balance between the adhesiveness and the cohesiveness of the adhesive layer to the extent that the adhesive does not cause cohesive failure. Here, the numerical values of the above-mentioned conditions a and b do not mean that the physical properties of the patch significantly change from the values. However, a patch that meets at least the above conditions a and b has sufficient adhesive strength and does not cause cohesive failure that cannot be put to practical use (that is, it has an excellent balance between adhesiveness and cohesiveness). ).

In addition, whether the cohesive failure phenomenon occurs in the pressure-sensitive adhesive layer when the patch of the present invention is applied and then peeled off is determined as follows.

First, when the adhesive strength of the patch is measured as described above, it is visually observed whether or not the adhesive is partially or partially left on the peeled test surface. The degree of cohesive failure of the pressure-sensitive adhesive layer is determined by the degree of residual pressure-sensitive adhesive. When the cohesive failure of the pressure-sensitive adhesive layer cannot be determined by this method, the following chalk powder test is employed. That is, chalk powder (particularly, colored chalk powder) is sprinkled on the test surface from which the patch has been peeled, and the state of powder adhesion is observed. When chalk powder adheres significantly to the test surface, it is recognized that the adhesive layer of the patch has undergone cohesive failure.

(Examples) Examples of the present invention will be described below.

Example 1 (1-1) Synthesis of Polymer 2-Ethylenehexyl Acrylate (Main Monomer) 18
4.0 parts by weight Methacrylic acid (auxiliary monomer) 6.0 parts by weight Ethyl acetate 170 parts by weight n-Hexane 10 parts by weight The above formulation was charged into a reaction vessel, and in a N ₂ gas stream at 60 ° C. for 8 hours and at 70 ° C. for 8 hours, And the reflux temperature of the system (about 73 ℃)
Each reaction was allowed to polymerize at 8 hours. In the reaction vessel, as a polymerization catalyst, 0.4 mol% of the total amount of the above monomers
Of azobisisobutyronitrile was added in 8 portions within 18 hours. In the final 6 hours of the total reaction time of 24 hours, stirring and reflux were performed to sufficiently decompose the catalyst and complete the reaction. After the polymerization reaction, a viscous polymer solution was obtained. The intrinsic viscosity (30 ° C., toluene solvent system) of this polymer solution was 1.684. The glass transition temperature (Tg) of the obtained polymer was about -53 ° C by the DSC method.

(1-2) Preparation of pressure-sensitive adhesive solution Additional ethyl acetate was added to the polymer solution obtained in (1-1) to prepare a 40% ethyl acetate solution. This solution 10
Dioctyl phthalate 1 as a Tg lowering agent per 0 part by weight
An adhesive solution was prepared by adding 6 parts by weight so that Tg (after drying) was about −83 ° C.

(1-3) Preparation of adhesive layer forming liquid Polymer component 100 of the adhesive solution obtained in (1-2)
An adhesive layer forming liquid was prepared by adding 8 parts by weight of a staple fiber (average diameter; about 12 μm: average fiber length about 25 mm) as a reinforcing fibrous filler per part by weight, and stirring and mixing. A desired patch can be obtained by adding a drug to this solution and coating it on the backing support.

(1-4) Preparation of pressure-sensitive adhesive sheet and its reinforcing property test The pressure-sensitive adhesive layer-forming liquid obtained in (1-3) was dried on a sheet-like backing support (EVA film; thickness 60 μm). A pressure-sensitive adhesive sheet was produced by casting and drying so that the thickness was about 55 μm or more. About 30mm x 30 from this adhesive sheet
Two mm samples were cut out, and each sample was attached to the chest of the human body at symmetrical positions. After 24 hours, when the state of the attached sample was observed, almost no seepage of the adhesive around the sample was observed. In addition, even though this pressure-sensitive adhesive sheet had a pressure-sensitive adhesive layer that was thick enough to cause a slight pain to the human body during peeling, no pressure-sensitive adhesive remained on the skin of the human body after peeling the sample. .

(1-5) Drug content test of adhesive agent Prepare a plurality of adhesive solution obtained in (1-2), and 1 part by weight, 2 parts by weight, 3 parts by weight of indomethacin as a drug per 100 parts by weight of each polymer component. Parts by weight and 1 part by weight were added and mixed at intervals of 1 part by weight. This mixture was cast on a transparent film such as a PET film, dried, and allowed to stand at 40 ° C. for 7 days, and the state of precipitation of drug crystals was examined by a microscope or the like. Then, the maximum number of parts to which the drug crystal was not added was determined. The maximum number of copies was 22 parts by weight. This numerical value is shown in Table 1 as the maximum drug content.

(1-6) Drug release test of adhesive agent Polymer component 100 of adhesive agent solution obtained in (1-2)
Indomethacin having the maximum drug content determined in (1-5) was added and mixed per part by weight. This mixture was evenly coated on a peelable sheet to a thickness of 70 μm and dried, and then a PET (polyethylene terephthalate) film was laminated and pressure-bonded. A circular test piece with a diameter of 6 cm was cut out from this laminate. The peelable sheet was peeled from this test piece, and the test piece was immersed in 100 ml of a mixed solvent of acetone-water (weight ratio: 50:50) at 30 ° C. for 6 hours for immersion. Then, the test piece was taken out from the mixed solvent, and the amount of the drug extracted in the solvent was quantified by the liquid chromatography method. The ratio (%) of the amount of the extracted drug to the amount of the drug calculated to be contained in the test piece was evaluated as the drug release property of the adhesive. The ratio of the extracted drug amount is
It was 71%. Table 2 shows the results.

(1-7) Adhesive holding force test From the adhesive sheet obtained in (1-4), width 25 ± 0.5 mm
JIS samples were cut out and the following conditions were used.
The holding power value (H) of the pressure-sensitive adhesive layer was tested according to -Z-0237 (holding power). However, when the sample was liable to stretch, a PET tape was attached to the backing support side of the sample to prevent easiness of stretching (rear surface reinforcement), and the test was performed.

Attached area of sample to test plate: 25mm x 25mm Hanging load: 1000g Temperature during test: 30 ± 1 ° C (heating) Measured value: After applying the load, the affixed part of the sample was “deviation”
Time until the load comes off (in seconds)
Is the holding force value (H). The holding power value was 964 (seconds).

(1-8) Adhesive strength test of adhesive From the adhesive sheet obtained in (1-4), width 25 ± 0.5 mm
JIS samples were cut out and the following conditions were used.
The adhesive strength value (F) of the adhesive layer was tested according to -Z-0237 (180 degree peeling adhesion). However, if necessary, the back surface of the sample was reinforced as in (1-7).

Temperature during the test: 23 ± 2 ° C (room temperature) Measured value: It is displayed in g (gram) of the load to be peeled off. The adhesive strength value was 287 (g / 25 mm).

The value of H / F was calculated based on the holding power value (H) and the adhesive power value (F) obtained in the holding power test (1-7) and the adhesive power test, respectively. H / F was 3.36. In this adhesive strength test, the cohesive failure of the pressure-sensitive adhesive after peeling was visually observed, and no cohesive failure of the pressure-sensitive adhesive was observed. Table 3 shows the results.

Comparative Example 1-1 A polymer solution was synthesized and an adhesive solution was prepared in the same manner as in (1-1) and (1-2) of Example 1. (1-3) and (1-4) of Example 1 except that no reinforcing fibrous filler was added to this adhesive solution.
A pressure-sensitive adhesive layer forming liquid was prepared and a pressure-sensitive adhesive sheet was prepared in the same manner as in. For this pressure-sensitive adhesive sheet, (1
A reinforcing property test was conducted in the same manner as in (4). As a result, the bleeding width of the adhesive around the sample was 3 mm or more on the part where the human body was attached. Further, after the sample was peeled off, the adhesive layer remained on the skin of the human body due to cohesive failure of the adhesive layer, resulting in stains.

Comparative Example 1-2 A polymer solution was synthesized in the same manner as in (1-1) of Example 1. With respect to this polymer solution (Tg lowering agent and reinforcing fibrous filler were not added: Tg was about −53 ° C.), a drug content test of an adhesive was conducted by the same method as in (1-5) of Example 1. I went. The maximum number of parts in which drug crystals did not precipitate was 10 parts by weight. This numerical value is shown in Table 1 as the maximum drug content.

Comparative Example 1-3 A polymer solution was synthesized in the same manner as in Example 1. With respect to this polymer solution, a drug release test of the pressure-sensitive adhesive was carried out by the same method as in (1-6) of Example 1 with reference to the maximum drug content calculated in Comparative Example 1-2. The ratio of the extracted drug amount was 49%. The results are shown in Table 2.

Comparative Example 1-4 A polymer solution was synthesized and a pressure-sensitive adhesive solution was prepared in the same manner as in (1-1) and (1-2) of Example 1. (1-3) and (1-4) of Example 1 except that no reinforcing fibrous filler was added to this adhesive solution.
A pressure-sensitive adhesive layer forming liquid was prepared and a pressure-sensitive adhesive sheet was prepared in the same manner as in. For this pressure-sensitive adhesive sheet, (1
By the same method as -7) and (1-8), the coercive force value (H) and the cohesive force value (F) of the adhesive layer were measured, and the H / F value was calculated. Holding power value is 75 (sec), adhesive strength value is 325-780 (g / 25mm), and H / F is 0.23
Met. The variation in the adhesive strength value is recognized because of the tendency of the adhesive layer to undergo cohesive failure. Further, the cohesive failure of the pressure-sensitive adhesive after being peeled off in this adhesive strength test was visually observed, and a slight cohesive failure of the pressure-sensitive adhesive was observed. Table 3 shows the results.

Example 2 (2-1) Synthesis of polymer 92.0 parts by weight of acrylic acid-n-octyl (main monomer-1) 99.0 parts by weight of acrylic acid-n-nonyl (main monomer-2) Acrylic acid (auxiliary monomer) 5.0 parts by weight Ethyl acetate 140 parts by weight n-Hexane 20 parts by weight The above formulation was charged into a reaction vessel, and in a N ₂ stream, at 60 ° C for 8 hours, 70 ° C for 8 hours, and the reflux temperature of the system (about 74 ° C).
Each reaction was allowed to polymerize at 8 hours. In the reaction vessel, as a polymerization catalyst, 0.3 mol% of the total amount of the above monomers
Lauroyl peroxide was added in 8 portions within 18 hours. In the final 6 hours of the total reaction time of 24 hours, stirring and reflux were performed to sufficiently decompose the catalyst and complete the reaction. After the polymerization reaction, a viscous polymer solution was obtained. The intrinsic viscosity (toluene solvent system) of this polymer solution is 1.711.
And Tg was about -62 ° C.

(2-2) Preparation of adhesive solution Additional ethyl acetate was added to the polymer solution obtained in (2-1) to prepare a 40% ethyl acetate solution. This solution 10
18 parts by weight of olive oil was added as a Tg lowering agent per 0 parts by weight to prepare an adhesive solution so that Tg (after drying) was −88 ° C.

(2-3) Preparation of adhesive layer forming liquid Polymer component 100 of the adhesive solution obtained in (2-2)
As the reinforcing fibrous filler, 12 parts by weight of borane-treated glass short fibers (average diameter; 8 μm, average fiber length; 30 μm) were added per part by weight, and the mixture was stirred and mixed to form an adhesive layer. A forming liquid was prepared. A desired patch can be obtained by adding a drug to this solution and coating it on the backing support.

(2-4) Production of pressure-sensitive adhesive sheet and its reinforcing property test A pressure-sensitive adhesive sheet was produced in the same manner as in Example 1 except that the pressure-sensitive adhesive layer-forming liquid obtained in (2-3) was used, The reinforcing property test was conducted. As a result, the exudation of the adhesive to the periphery of the sample was hardly seen. In addition, even though this adhesive sheet has an adhesive layer with a thickness (about 55 μm or more) that causes a slight pain to the human body during peeling, the adhesive remains on the human skin after peeling the sample. Was not recognized.

(2-5) Adhesive drug content test The maximum number of parts in which drug crystals did not precipitate was determined by the same method as in Example 1 except that the adhesive solution obtained in (2-2) was used. . The maximum number of copies was 24 parts by weight.
This numerical value is shown in Table 1 as the maximum drug content.

(2-6) Drug release test of pressure sensitive adhesive For the pressure sensitive adhesive solution obtained in (2-2), (2-5)
The drug releasing property of the pressure-sensitive adhesive was evaluated by the same method as in Example 1 except that the maximum drug content of indomethacin calculated in 1. was added. The ratio of the extracted drug amount is 78%
Met. Table 2 shows the results.

(2-7) Retention force test of pressure-sensitive adhesive Retention force value (H) of pressure-sensitive adhesive layer in the same manner as in Example 1 except that the pressure-sensitive adhesive sheet obtained in (2-4) was used.
Was measured. The holding power value was 1196 (seconds).

(2-8) Adhesive Strength Test of Adhesive Adhesive strength value (H) of adhesive layer in the same manner as in Example 1 except that the adhesive sheet obtained in (2-4) was used.
Was measured. The adhesive strength value was 335 (g / 25 mm).

The value of H / F was calculated based on the holding force value (H) and the adhesive force value (F) obtained in the holding force test (2-7) and the adhesive force test, respectively. H / F was 3.57. In this adhesive strength test, the cohesive failure of the pressure-sensitive adhesive after peeling was visually observed, and no cohesive failure of the pressure-sensitive adhesive was observed. Table 3 shows the results.

Comparative Example 2-1 A polymer solution was synthesized and an adhesive solution was prepared in the same manner as in (2-1) and (2-2) of Example 2. (2-3) and (2-4) of Example 2 except that no reinforcing fibrous filler was added to this adhesive solution.
A pressure-sensitive adhesive layer forming liquid was prepared and a pressure-sensitive adhesive sheet was prepared in the same manner as in. For this pressure-sensitive adhesive sheet, (1
A reinforcing property test was conducted in the same manner as in (4). As a result, the adhesive vigorously exuded around the sample at the attachment site on the human body. In addition, after the sample was peeled off, the adhesive layer remained on the skin of the human body due to cohesive failure of the adhesive layer, resulting in stains.

Comparative Example 2-2 A polymer solution was synthesized in the same manner as in Example 2 (2-1). For this polymer solution (Tg lowering agent and reinforcing fibrous filler were not added: Tg was about −62 ° C.), the adhesive content of the adhesive was tested by the same method as in (1-5) of Example 1. I went. The maximum number of parts in which drug crystals did not precipitate was 12 parts by weight. This value is shown in Table 1 as the maximum drug content.

Comparative Example 2-3 A polymer solution was synthesized in the same manner as in (2-1) of Example 2. Regarding this polymer solution, (1 in Example 1)
In the same manner as in (6), a drug release test of the pressure-sensitive adhesive was performed with reference to the maximum drug content calculated in Comparative Example 2-2. The ratio of the extracted drug amount was 52%. The results are shown in Table 2.

Comparative Example 2-4 A polymer solution was synthesized and an adhesive solution was prepared in the same manner as in (2-1) and (2-2) of Example 2. (2-3) and (2-4) of Example 2 except that no reinforcing fibrous filler was added to this adhesive solution.
A pressure-sensitive adhesive layer forming liquid was prepared and a pressure-sensitive adhesive sheet was prepared in the same manner as in. For this pressure-sensitive adhesive sheet, (1
By the same method as -7) and (1-8), the coercive force value (H) and the cohesive force value (F) of the adhesive layer were measured, and the H / F value was calculated. Holding power value is 76 (sec), adhesive strength value is 364-1040 (g / 25mm), and H / F is 0.21
Met. The variation in the adhesive strength value is recognized because of the tendency of the adhesive layer to undergo cohesive failure. Further, the cohesive failure of the pressure-sensitive adhesive after being peeled off in this adhesive strength test was visually observed, and a slight cohesive failure of the pressure-sensitive adhesive was observed. Table 3 shows the results.

Example 3 (3-1) Synthesis of polymer 92 parts by weight of acrylic acid-n-octyl (main monomer-1) 106 parts by weight of n-decyl methacrylate (main monomer-2) hexanediol dimethacrylate (auxiliary monomer)
0.01 parts by weight Ethyl acetate 100 parts by weight n-Hexane 20 parts by weight The above formulation was charged into a reaction vessel, and in a stream of N ₂ at 60 ° C. for 8 hours, 70 ° C. for 8 hours, and the system reflux temperature (about 75 ° C.). )
Each reaction was allowed to polymerize at 8 hours. In the reaction vessel, as a polymerization catalyst, 0.25 mol% of the total amount of the above monomers
Benzoyl peroxide was added in 8 portions over 18 hours. In the final 6 hours of the total reaction time of 24 hours, stirring and reflux were performed to sufficiently decompose the catalyst and complete the reaction. After the polymerization reaction, a viscous polymer solution was obtained.
The intrinsic viscosity (toluene solvent system) of this polymer solution is 1.79.
7 and Tg was about -67 ° C.

(3-2) Preparation of adhesive solution Additional ethyl acetate was added to the polymer solution obtained in (3-1) to prepare a 40% ethyl acetate solution. This solution 10
Dioctyl sebacate 1 as a Tg lowering agent per 0 parts by weight
An adhesive solution was prepared by adding 2 parts by weight so that Tg (after drying) would be −85 ° C.

(3-3) Preparation of adhesive layer forming liquid Polymer component 100 of the adhesive solution obtained in (3-2)
Per part by weight, as a reinforcing fibrous filler, polyacrylonitrile short fibers (average diameter; 15 μm, average fiber length; 15 m
18 parts by weight of m) was added, and the mixture was stirred and mixed to prepare an adhesive layer forming liquid. Add the drug to this solution,
When applied on a backing support, the desired patch is obtained.

(3-4) Production of pressure-sensitive adhesive sheet and its reinforcing property test A pressure-sensitive adhesive sheet was produced in the same manner as in Example 1 except that the pressure-sensitive adhesive layer-forming liquid obtained in (3-3) was used. The reinforcing property test was conducted. As a result, no displacement of the patch or exudation of the adhesive around the sample was observed. In addition, it was not observed that the adhesive remained on the skin of the human body after peeling the sample.

(3-5) Drug content test of adhesive agent The maximum number of copies in which drug crystals did not precipitate was determined by the same method as in Example 1 except that the adhesive solution obtained in (3-2) was used. . The maximum number of copies was 21 parts by weight.
This numerical value is shown in Table 1 as the maximum drug content.

(3-6) Adhesive drug release test For the adhesive solution obtained in (3-2), (3-5)
The drug releasing property of the pressure-sensitive adhesive was evaluated by the same method as in Example 1 except that the maximum drug content of indomethacin calculated in 1. was added. 74% of the extracted drug amount
Met. Table 2 shows the results.

(3-7) Retention force test of pressure-sensitive adhesive Retention force value (H) of pressure-sensitive adhesive layer in the same manner as in Example 1 except that the pressure-sensitive adhesive sheet obtained in (3-4) was used.
Was measured. The holding power value was 1057 (seconds).

(3-8) Pressure-sensitive adhesive strength test of pressure-sensitive adhesive The pressure-sensitive adhesive strength value (H) of the pressure-sensitive adhesive layer in the same manner as in Example 1 except that the pressure-sensitive adhesive sheet obtained in (3-4) was used.
Was measured. The adhesive strength value was 341 (g / 25 mm).

The value of H / F was calculated based on the holding force value (H) and the adhesive force value (F) obtained in the holding force test (3-7) and the adhesive force test, respectively. The H / F was 3.10. In this adhesive strength test, the cohesive failure of the pressure-sensitive adhesive after peeling was visually observed, and no cohesive failure of the pressure-sensitive adhesive was observed. Table 3 shows the results.

Comparative Example 3-1 A polymer solution was synthesized and an adhesive solution was prepared in the same manner as in Example 3 (3-1) and (3-2). (3-3) and (3-4) of Example 3 except that no reinforcing fibrous filler was added to this adhesive solution.
A pressure-sensitive adhesive layer forming liquid was prepared and a pressure-sensitive adhesive sheet was prepared in the same manner as in. For this pressure-sensitive adhesive sheet, (1
A reinforcing property test was conducted in the same manner as in (4). As a result, at the location where the human body was stuck, due to insufficient cohesive strength of the pressure sensitive adhesive, slippage of the pressure sensitive adhesive and bleeding of the pressure sensitive adhesive around the sample were observed. After the sample was peeled off, the adhesive remained on the skin of the human body and became dirty.

Comparative Example 3-2 A polymer solution was synthesized in the same manner as in Example 3 (3-1). With respect to this polymer solution (Tg lowering agent and reinforcing fibrous filler were not added: Tg was about -67 ° C), a drug content test of an adhesive was conducted by the same method as in (1-5) of Example 1. I went. The maximum number of parts in which drug crystals did not precipitate was 14 parts by weight. This numerical value is shown in Table 1 as the maximum drug content.

Comparative Example 3-3 A polymer solution was synthesized in the same manner as in (3-1) of Example 3. Regarding this polymer solution, (1 in Example 1)
By the same method as in (6), a drug release test of the pressure-sensitive adhesive was performed with reference to the maximum drug content calculated in Comparative Example 3-2. The ratio of the extracted drug amount was 58%. The results are shown in Table 2.

Comparative Example 3-4 A polymer solution was synthesized and a pressure-sensitive adhesive solution was prepared in the same manner as in (3-1) and (3-2) of Example 3. (3-3) and (3-4) of Example 3 except that no reinforcing fibrous filler was added to this adhesive solution.
A pressure-sensitive adhesive layer forming liquid was prepared and a pressure-sensitive adhesive sheet was prepared in the same manner as in. For this pressure-sensitive adhesive sheet, (1
By the same method as -7) and (1-8), the coercive force value (H) and the cohesive force value (F) of the adhesive layer were measured, and the H / F value was calculated. Holding force value is 102 (sec), adhesive force value is 360-715 (g / 25mm), and H / F is 0.28
Met. The variation in the adhesive strength value is recognized because of the tendency of the adhesive layer to undergo cohesive failure. In addition, the state of cohesive failure of the pressure-sensitive adhesive after being peeled off in this pressure-sensitive adhesive strength test was visually observed, but cohesive failure of the pressure-sensitive adhesive was recognized, although it was very slight. Table 3 shows the results.

As is clear from the examples and comparative examples, the patch of the present invention contains a reinforcing fibrous filler in the pressure-sensitive adhesive layer, and therefore has an excellent balance between tackiness and cohesiveness. This means that the adhesive strength value (F) of the patch is 200 g or more,
It is proved from the ratio of holding force value (H) to adhesive force value (F): H / F> 0.3 sec / g. Therefore, even if this patch is applied to a human body, the exudation of the adhesive is small. Moreover, the adhesive does not remain on the skin of the human body after the patch is peeled off. The patch of the present invention further has a glass transition temperature (Tg)
Since the pressure-sensitive adhesive layer is composed of a pressure-sensitive adhesive having a temperature of −71 ° C. or less, a large amount of the drug can be contained in the pressure-sensitive adhesive layer and the drug release is excellent.

An adhesive patch that does not contain a reinforcing fiber filler in the adhesive layer has a poor balance between adhesiveness and cohesiveness, and its adhesive strength is 20
Retention force value (H) and adhesive force value (F) even though it is 0 g or more
Ratio: H / F ≦ 0.3 sec / g. Therefore, when this patch is applied to a human body, the adhesive oozes out to the peripheral portion, and the patch remarkably shifts. Moreover, after peeling off the patch, the adhesive remains on the skin of the human body and becomes dirty. Glass transition temperature (T
A patch having a pressure-sensitive adhesive layer composed of a pressure-sensitive adhesive whose g) exceeds -71 ° C cannot contain a large amount of drug in the pressure-sensitive adhesive layer. Moreover, the release of the drug from the adhesive layer is also poor.

(Effect of the invention) In the patch of the present invention, since the novel acrylic acid ester-based polymer having a glass transition temperature (Tg) of −71 ° C. or less is used as the pressure-sensitive adhesive, the pressure-sensitive adhesive layer is A large amount of the drug is dissolved, and the drug is highly released. Moreover, since this patch contains a reinforcing fibrous filler in the pressure-sensitive adhesive layer, it has an excellent balance of tackiness and cohesiveness.
Therefore, if this patch is used, the drug efficacy is increased and the drug utilization efficiency is increased. It is economical because a large amount of drug can be contained in one patch. Furthermore, even when the patch is applied to the skin of the human body, the exudation of the adhesive and the displacement of the patch are small. Even if the skin is bent or stretched, the patch will not be displaced. The adhesive does not remain on the skin after peeling the patch. Therefore, according to this patch, the patient
No pain or discomfort. By combining the Tg value of the pressure-sensitive adhesive in the patch and the reinforcing fibrous filler, the selection range of the substance used as the material of the pressure-sensitive adhesive can be expanded.

Claims (1)

(57) [Claims] 1. A patch having a backing support layer and a pressure-sensitive adhesive layer, wherein the pressure-sensitive adhesive layer has a glass transition temperature (Tg) of -71 ° C. or less, a reinforcing fibrous filler, and Contains the drug,
The adhesive is mainly composed of a (meth) acrylic acid ester polymer, and the adhesive strength value (H) and the adhesive strength value (F) of the adhesive layer satisfy the following a formula and b formula. H / F> 0.3 (sec / g)… a F> 200 (g)… b