JPH03127727A - Pasting agent - Google Patents

Abstract

PURPOSE:To obtain pasting agent having excellent pasting property to skin and good balance of adhesive property and cohesive property comprising an adhesive mass layer of non-acrylic compound containing abundant dissolved drug and exhibiting high releasability and a backing supporter layer. CONSTITUTION:Reinforcing filler (e.g. fine powdered silicic anhydride) and a drug are contained in non-acrylic compound having a glass transition temperature (Tg) below -71 deg.C (e.g. polybutadiene rubber or beta-pinene) as an adhesive mass. Then, an age resistor and stabilizer, etc., are added to said composition, as necessary, to obtain an adhesive mass layer. Thus, a backing supporter layer composed of supporter such as nonwoven cloth and said adhesive mass layer are used as principal components and releasabilityprotecting paper or sheet is adhered on the surface of said adhesive mass layer to afford the aimed article. Besides, value of holding force (H) and value of adhesive force (F) of said adhesive mass layer satisfy the relation of H/F>0.3(sec/g) and F>200(g).

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a patch in which a large amount of a drug is dissolved and is provided with an adhesive layer that has a high drug release property. The adhesive layer of this patch has excellent adhesion to the skin and has a good balance of adhesiveness and cohesiveness.

(Prior Art) Many patches have been proposed for a long time, which are applied to the skin by utilizing the adhesive properties of an adhesive containing a drug to exert the medicinal effects of the drug. ``This type of patch generally consists of a backing support layer and an adhesive layer containing an adhesive and a drug. The drug exists in the adhesive layer in a dissolved state, a dispersed state, a dispersed state in microcapsules, a state enclosed in a septum container, or the like. Examples of such patches include:
A skin disease treatment patch consisting of an adhesive layer and a base material containing an anti-inflammatory corticosteroid and a specific acrylic copolymer (Japanese Patent Publication No. 52-18813, Teijinsha), an anti-inflammatory steroid and an acrylic copolymer An adhesive tape comprising a pressure-sensitive adhesive material containing a copolymer formed on an impermeable support film (Japanese Patent Publication No. 52-31405, Eli Lilly & Co.), a backing member and a pressure-sensitive adhesive layer. death,
Furthermore, a medical bandage with a drug storage layer (Special Publication Act, 1973-
16566, Stephen David Goldby), a pharmaceutical component comprising a carrier and a drug-containing adhesive layer mainly composed of a specific acrylic acid ester copolymer (Japanese Unexamined Patent Publication No. 56-4)
No. 5412, Nitto Denko Corporation), and glass transition temperature (T
g) A pharmaceutical preparation formed by forming a base containing a polymer having a temperature of -70°C to -io'c and propyl nitrate on a carrier (Japanese Unexamined Patent Publication No. 57-183714, Nitto Denko Corporation) is mentioned. It will be done.

However, the physical properties of the adhesives used in these patches are different from those of other conventional adhesive tapes (e.g., general stationery tape, packaging tape, plastic tape such as insulating vinyl, industrial tape). It is no different from the adhesive used. For example, the glass transition temperature (Tg) of this type of adhesive is in the range of -70°C to -15°C. Adhesives with glass transition temperatures (Tg) outside this range are considered to be unsuitable for practical use in terms of adhesiveness, retention, and the like. However, adhesives having a Tg in this range generally have poor compatibility with drugs and cannot contain a sufficient amount of drugs. Even when attempts are made to incorporate a large amount of drug into an adhesive, the adhesive cannot sufficiently dissolve the drug. Even a small amount of dissolved drug is difficult to migrate and diffuse into the adhesive. Therefore, the drug release property of the adhesive layer is low, and the rate at which the drug reaches the skin surface and is absorbed into the skin is small. Therefore, even if a patch having such an adhesive layer is applied to the skin, sufficient medicinal efficacy cannot be obtained.

(Problems to be Solved by the Invention) The present invention solves the above-mentioned conventional problems, and its purpose is to provide a patch that dissolves a large amount of drug and has an adhesive layer with high drug release properties. Our goal is to provide the following. Another object of the present invention is to provide a patch that is well adapted to the skin and has excellent adhesion. Still another object of the present invention is to provide a patch with a good balance between adhesiveness and cohesiveness.

(Means for Solving the Problems) The present invention improves the compatibility between the adhesive and the drug by using an adhesive with a glass transition temperature (Tg) of -71'C or less, which has not been used until now. A large amount of drug can be dissolved in the adhesive layer because of the remarkable improvement; the drug dissolved in the adhesive layer has high release properties because it is easy to migrate and diffuse; It has good adhesion and adhesion (for example, the patch does not slip easily even when the skin is stretched and shrunk); and by adding a reinforcing filler to this adhesive, it is possible to create an adhesive with a low Tg. This was completed based on the inventor's knowledge that the disadvantages of using the adhesive were improved and the balance between the adhesive and cohesive properties of the adhesive layer was maintained.

The adhesive patch of the present invention has a backing support layer and an adhesive layer, and the adhesive layer has a glass transition temperature (Tg
) contains an adhesive, a reinforcing filler, and a drug whose temperature is -71°C or less, the adhesive is mainly composed of a non-acrylic compound, and the adhesive layer has a holding force value (H) and an adhesive force value of (F) satisfies the following relationships of formulas a and b, thereby achieving the above object.

H/F>0.3 (sec/g) ... aF>20
0 (g) ... b. (In the adhesive patch of the invention, a large amount of Drugs can be dissolved in adhesives.Drugs dissolved in adhesives migrate and diffuse easily, so they also have high release properties.This is because drug molecules are free and actively move in adhesives with a low Tg. The adhesive layer containing such a low Tg adhesive also has excellent adhesion to the skin.

It is presumed that this is because the polymer molecules that mainly constitute this adhesive tend to move in segment units. Furthermore, since the cohesive force of the adhesive decreases as the Tg decreases, a reinforcing filler is contained in this adhesive layer in order to maintain the cohesive force.

This improves various defects that occur in the adhesive layer due to a decrease in cohesive force (for example, oozing, shearing, stringiness, and adhesive remaining on the skin). As a result, a patch having an adhesive layer with a well-balanced adhesiveness and cohesiveness can be obtained. This adhesive has good adhesion to the skin,
It also has excellent adhesion.

Furthermore, by selecting the composition and content of the adhesive, reinforcing filler, and drug, patches with various physical properties depending on the purpose can be provided.

In order to obtain an adhesive with a glass transition temperature (Tg) of -71"C or lower, it is first thought to use a non-acrylic compound with a Tg of -71"C or lower.However, in reality, the Tg is -71"C or lower. By adding a softener or the like that has a 7g lowering effect (7g lowering agent) to a non-acrylic compound that exceeds Therefore, in order to reduce the amount of the 7g lowering agent added, a non-acrylic compound whose Tg is close to -71°C is used even if it is 171°C or higher.

The adhesive used in the patch of the present invention is mainly composed of non-acrylic compounds. Examples of the non-acrylic compound include a rubber compound having a repeating unit of butadiene or isoprene in the main chain, a polyisobutylene compound, a polyvinyl ether compound, a polyurethane compound, or a mixture thereof. Acrylic compounds are generally used as adhesives for patches because of their low or non-irritating properties, adhesion to the skin, resistance to deterioration, compatibility with many drugs, and ease of molding. is considered optimal. However, these non-acrylic compounds also have excellent hypoallergenic or non-irritating properties and adhesion to the skin comparable to acrylic compounds, and can be applied without solvent or at high concentration. Furthermore, non-acrylic compounds are less expensive than acrylic compounds.

Rubber compounds having butadiene or isoprene repeating units in the main chain include, for example, natural or synthetic polyisoprene rubber, styrene-isoprene random copolymer rubber, styrene-butadiene block copolymer rubber, and styrene-isoprene block copolymer rubber. Included are rubber, polybutadiene rubber, etc., and mixtures thereof. Among these compounds, diene rubber (in the above example, a rubber having butadiene as a constituent unit) is preferred because it has the lowest Tg. Such a mixture of diene rubber and other rubber has a Tgl of -71'C or less or a Tg close to -71'C even if it is 71'C or higher, so the amount of 7g lowering agent added is small. Good and desirable. This rubber compound is usually blended with the following resin components and used as a rubber-resin compound. This resin component includes, for example, a tackifier for rubber. The softening temperature of this rubber tackifier is in the range of 25°C to 150°C. Examples of rubber tackifiers include rosin resins such as ester gum, α-pinene and β-
Terpene resins obtained by polymerizing terpenes such as pinene, polymer resins obtained from various fractions from petroleum refining (this includes aliphatic hydrocarbon resins, alicyclic hydrocarbon resins, and aromatic hydrocarbon resins) ). Other additives added to the rubber compound include a liquid 7g-lowering agent, a rubber anti-aging agent, and a crosslinking agent.

Polyisobutylene compounds are compounds mainly composed of inbutylene polymers. This compound is prepared, for example, by mixing a rubbery polymer having a molecular weight of about 50,000 or more with a semi-liquid or liquid polymer having a molecular weight of about 10,000 or less. If necessary, isobutylene-isoprene copolymer rubber may be added to this compound. To this compound, if necessary, rubber tackifier-1 liquid 7g-lowering agent, anti-aging agent, cross-linking agent, etc. may be added.

Polyvinyl ether compounds include polyvinylethyl ether compounds and polyvinyl isobutyl ether compounds. Both compounds are prepared by mixing an elastomeric polymer and a viscous liquid polymer. This compound can also be used with rubber tackifiers if necessary.
One-part 7g-lowering agents, anti-aging agents, cross-linking agents, etc. may be added.

Although various compounds are used as polyurethane compounds, for example, a liquid prepolymer whose main chain is 1,4-butadiene and has hydroxyl groups at both ends, and a liquid prepolymer whose main chain is 1.4-butadiene and hydroxyl groups at both ends.
4-butadiene and a liquid prepolymer having isocyanate groups at both ends in an appropriate ratio (-〇H group nee NCO
It is obtained by reacting with group=1:OJ~1:1.2). A liquid 7g-lowering agent, a crosslinking accelerator, etc. may be added to this compound as well. This polyurethane compound is preferred because it can be coated onto the backing support in a solvent-free system.

A compound compatible with non-acrylic compounds is used as the 7g lowering agent added to adjust the Tg of the adhesive to -71°C or less. Examples of the 7g lowering agent include phthalate ester plasticizers such as dibutyl phthalate and dioctyl phthalate; sebacate ester plasticizers such as dibutyl sebacate; adipic acid ester plasticizers such as dioctyl adipate; Phosphate ester plasticizers such as phosphate and trioctyl phosphate; Naturally derived glycerol triester plasticizers such as castor oil; Vegetable oils such as olive turquoise; and enoate ester plasticizers such as triethyl citrate. ; Liquid plasticizers such as liquid polyethers; Ester compounds such as isopropyl myristate, triethyl citrate, glycerin triacetate, polypropylene (generally polyalkylene), uricol dialkyl esters; polyalkylene glycol dialkyl ethers; aliphatic or alicyclic hydrocarbon oil; branched bolib-1-tadiene; and liquid polyisoprene. These 7
G-lowering agents are typically included up to 70% depending on the composition of the non-acrylic compound. If the amount of the 7g-lowering agent added is too large, the resulting adhesive layer will become too soft and sufficient cohesiveness will not be obtained.

The reinforcing filler is organic or inorganic.

This reinforcing filler may be fibrous or non-fibrous.

Examples of inorganic fibrous fillers include glass fibers and asbestos fibers. Inorganic, non-fibrous fillers include, for example, finely powdered silicic anhydride (usually called finely powdered Noriyoku or white capon), finely powdered diatomaceous earth, finely powdered carunium carbonate, zinc white, carbon black, etc. There is. Organic fillers include fibrous fillers and non-fibrous fillers, such as cellulose, cellulose derivatives (cellulose acetate, ethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, etc.)
, polyvinyl chloride, polymethyl poly(meth)acrylate, poly(meth)acrylonitrile, poly(meth)acrylamide, polystyrene, polyvinyl acetate, polypropylene, polyethylene, polyvinylidene chloride, polyester, polyamide, and the like. Natural organic non-fibrous fillers such as micronized polysaccharide compounds such as diquitin, chitosan, pectin, starches, gum arabic, konjac mannan, etc. may also be used. Preferably, the fibrous reinforcing filler has an average diameter of 20 μm or less (desirably 10 μm or less) and an average fiber length of 1 mm to 25 mm. Further, the non-fibrous reinforcing filler has an average diameter of 30 μm or less, preferably 10 μm or less.

The surface of these reinforcing fillers may be subjected to various treatments, if necessary, in order to improve their surface activity (eg, adhesion). These treatments include, for example, surface electron beam irradiation, surface ion blating, surface chemical treatment, or surface coating.

Drugs added to the adhesive include, for example, analgesic anti-inflammatory agents, steroid hormones, anti-allergy agents, antihistamines, coronary vasodilators, calcium antagonists, anti-bacterial agents, antibiotics, antidotes, antitussives, and antipruritic agents. drugs, hypnotics, mental vitality agents, sei-sei stabilizers, blood pressure regulators, diuretics, asthmatics, antiepileptics, hormone secretagogues, antiulcer agents, stone dissolvers, anticancer agents, vitamins, blood circulation promoters, Examples include anesthetics.

The adhesive layer of the patch of the present invention may contain antioxidants, antioxidants, tackiness improvers, drug absorption promoters, stabilizers, surfactants, dyes, pigments, etc., as necessary. You can. Antiaging agents and stabilizers are used in appropriate amounts to prevent aging and stabilize adhesives, drugs, and additives. Since the adhesive used in the present invention has a Tg of 171° C. or less, it has excellent drug transfer and absorption effects, but in order to further enhance these effects, a drug transfer and absorption enhancer is added. In addition, a surfactant is used in an appropriate amount to promote wetting of the skin by the drug. Furthermore, although the adhesive layer is mainly composed of a non-(meth)acrylic acid alkyl ester polymer, approximately 30% of the total polymer component is
Other polymers, such as poly(meth)acrylate components, may be added to this polymer in the following amounts.

The support of the backing support layer includes all conventionally known and used materials. Particularly preferred are plastic films or sponge sheets having flexibility and extensibility, flexible woven fabrics, knitted fabrics, nonwoven fabrics, or laminates thereof. For example, materials for the support include polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer (E
VA), polyethylene (especially low density polyethylene),
Polybutadiene, styrene-butadiene or styrene-isoprene-based block copolymer resins, butadiene-styrene-methyl methacrylate (MMA) copolymer resins, nylon, polyurethane, alkoxyalkyl (
meth)acrylate copolymer, polyvinyl acecool,
Used are cellulose derivatives such as plasticized cellulose acetate and ethyl cellulose, polyamino acids, and water-insoluble water-soluble polymers (eg, pululane, polyvinylpyrrolidone). The thickness of the support is 30 to 300 μm in the case of a film.

For sponge sheets, woven fabrics, knitted fabrics, and non-woven fabrics, OJ ~ 3m
It is assumed that m.

The adhesive patch of the present invention mainly includes a backing support layer and an adhesive layer, and is provided with a releasable protective paper or sheet attached to the surface of the adhesive layer. The removable protective paper or sheet is sterilized.

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

(i) An adhesive solution (or liquid adhesive) is applied onto the backing support and dried to form an adhesive layer. In this case, this adhesive layer may or may not contain a drug. A drug solution is sprayed or applied onto this adhesive layer. After drying the adhesive layer again, removable protective paper is attached to the surface of the adhesive layer, and the product is cut and packaged for use. However, if the adhesive solution contains a drug in advance, the steps of spraying or applying the drug solution and redrying the adhesive layer are not necessary.

6 (if) An adhesive solution (or liquid adhesive) is applied on the releasable side of the releasable protective paper and dried to form an adhesive layer. A drug solution is sprayed or applied onto this adhesive layer. After drying the adhesive layer again, a backing support is laminated and pressed onto the surface of the adhesive layer, and the product is cut and packaged for use. However, if the adhesive solution contains a drug in advance, the steps of spraying or applying the drug solution and redrying the adhesive layer are not necessary.

In the patch of the present invention thus obtained, an adhesive,
As described above, the holding force value (H) and adhesive force value (F) of the adhesive layer containing a reinforcing filler and a drug have the following relationships of formulas a and b.

H/F>OJ (sec/g) ... aF>200g
... b Here, formula a indicates that cohesive failure does not occur in the adhesive layer, and formula s indicates that the adhesive layer has sufficient adhesive strength. Retention force value of adhesive layer (
H) and adhesive force value (F) are measured as follows.

7- (a) Holding force value (H) JIS-Z-0237 (
The holding force value (H) of the adhesive layer was tested according to the holding force).

Size of sample: Width 25 ± 0.5 mm Area of sample attached to test plate: 25 mm x 25 mm Suspended load: 1000 g Temperature during test: 30 ± 1°C (heated) Measured value: After applying the load, The part where the sample is pasted is “misaligned”
time (seconds) until it comes off and the load falls.
is the holding force value (H). However, the measurement is limited to 18,000 seconds (5 hours).

(b) Adhesive force value (F) JIS-Z-0237 (
The adhesive force value (F) of the adhesive layer was tested according to the 180 degree peeling method (adhesion force).

Sample size: 25 ± 0.5 mm in width Temperature during test: 23 ± 2°C (room temperature) Measured value: Displayed in g (duram) of the load at which peeling occurs.

=18= The above-mentioned holding force value (H) and adhesive force value (F) serve as standards for the cohesive force and adhesive force of the adhesive layer, respectively. For example, if the holding force value (H) is low, the adhesive layer is likely to cause cohesive failure, and if the adhesive force value (F) is low, the adhesive layer has the necessary and sufficient adhesive force for application to the skin. I won't. However, since the cohesive force and the adhesive force are correlated with each other, even if the holding force value (H) and adhesive force value (F) of the adhesive layer are -values on the windowsill, it is not necessarily suitable for practical use. Not necessarily. For example, the holding force value (r-r) of the adhesive layer
Even if it shows a high value, it will show an even higher adhesive force value (F)
If it has, the adhesive will undergo cohesive failure. Conversely, even if the cohesive force value (H) of the adhesive layer is low, if the adhesive force value (F) is similarly low, the adhesive will not cause cohesive failure. For this reason, the above conditions are set so that the adhesive layer has a certain level of adhesive strength, and the balance between the adhesive and cohesive properties of the adhesive layer is maintained to the extent that the adhesive does not cause cohesive failure. In order to achieve this, the above condition a was set. Here, the numerical values of the above conditions a and b do not mean that the physical properties of the adhesive patch change significantly beyond these values. However, a patch that meets at least conditions a and b above has sufficient adhesive strength and does not cause cohesive failure that cannot be used in practical use (i.e., has an excellent balance between adhesiveness and cohesiveness). ).

Further, whether or not a cohesive failure phenomenon occurs in the adhesive layer when the adhesive patch of the present invention is applied and then peeled off is determined as follows.

First, when measuring the adhesive strength of a patch as mentioned above,
Visually observe whether the adhesive remains on the peeled test surface in a layered or partial manner.

The degree of cohesive failure of the adhesive layer is determined based on the degree of residual adhesive. If cohesive failure of the adhesive layer cannot be determined by this method, the following chalk powder test is used.

That is, chalk powder (
In particular, sprinkle colored chalk powder) and observe how the powder adheres. If chalk powder adheres significantly to the test surface, it is recognized that the adhesive layer of the patch has suffered cohesive failure.

(Example) 0- Examples of the present invention will be described below.

Cis-1,4-polybutadiene (97% purity: JSR
-BR-01) 70
Parts by weight Natural rubber (grade: pale crepe) 30 parts by weight Poly-β-pinene resin (Piccolite S-100: Softening point (00°C) 60 parts by weight Squalane (liquid plasticizer) 20 parts by weight 2.5-di- t-Amylhydroquinone (anti-aging agent)
1.5 parts by weight of the above formulation was added to cyclohexane and stirred and mixed to prepare a 30% cyclohexane solution. Here, the rubber component and resin component were cut or crushed to a suitable size or less before use. The Tg (after drying) of the resulting adhesive solution was 112°C.

1-2 To the adhesive solution obtained in 1-1>, fine powder 21 silicic anhydride (average particle size; 2 μm or less) and 24 parts by weight of acetylsalicylic acid (analgesic) as a drug were added, and the mixture was stirred and mixed to prepare a viscous adhesive paste.

■-3lI After applying corona treatment to one side of a soft polyethylene film with a thickness of 70 μm, the adhesive paste obtained in step (1-2) was applied to the treated side and dried, resulting in a film with a thickness of approx. A 50 μm adhesive layer was formed. A silicone release paper was applied to the surface of this adhesive layer.

1-4 Shellfish/Fish ・From the patch obtained in test (1-3), 20mm
A square test piece of mm size was cut out and attached to the outside of the upper arm of a human body. After 24 hours, the condition of the attached test piece was observed. As a result, approximately 1 mm at the periphery of the test piece
Although oozing of the adhesive plaster from the front and back was observed, no natural peeling was observed. When this test piece was peeled off from one end, there was a moderate peeling sensation (feeling of adhesion) to the human body.
I felt no pain. Further, when the test piece was peeled off, there was no stringing phenomenon, and no sticky paste was observed to remain on the human skin after the test piece was peeled off.

A circular test piece with a diameter of 60 mmφ was cut from the patch obtained in the release test (1-3) in Section 1-5. The peelable sheet was peeled off from this test piece, and a mixed solvent of ethyl alcohol and water (weight ratio; 50:50) was added.
It was soaked in 100ml by standing at 35℃ for 6 hours (
At this time, turn the adhesive layer side up).

Thereafter, the test piece was taken out from the mixed solvent, and the amount of drug extracted into the solvent was determined by liquid chromatography. The drug release property of the adhesive was evaluated as the ratio (%) of the released drug amount to the drug amount calculated to be contained in the test piece.The ratio of the released drug amount was 45%.
%Met. These results are shown in Table 1.

From the patch obtained in test (1-3) marked 1-6, width 25 ± 0.5 m +
J except that samples of n were cut and the following conditions were used:
The holding force 3 value (H) of the adhesive layer was tested according to IS-Z-0237 (holding force). However, if the sample stretches easily,
A PET tape was attached to the backing support side of the sample to prevent the sample from stretching easily (reinforcing the back surface), and the sample was subjected to the test.

Area of the sample pasted on the test plate: 25mm x 25mm Hanging load: 1000 g Temperature during test = 30±1℃ (heated) Measured value: After applying the load, the part of the sample pasted “slips”
time (seconds) until it comes off and the load falls.
is the holding force value (H). The holding force value was 662 (seconds).

1-7 From the patch obtained in the trial (1-3), a width of 25 ± 0.5 mm was obtained.
JI except that the sample was cut out and the following conditions were used.
The adhesive strength value (F) of the adhesive layer was tested according to S-Z-0237 (180 degree peeling method adhesive strength). However, if necessary, the back surface of the sample was reinforced in the same manner as in (1-6).

Temperature during test = 23 ± 2°C (room temperature) Measured value: Displayed in grams (durham) of the load at which peeling occurs. The adhesive strength value was 276 (g725mm).

The value of H/F was calculated based on the holding force value (H) and adhesive force value (F) obtained in the holding force test of 24-(1-6) and this adhesive force test, respectively. H/F is 2.40 seconds/g
Met. In addition, when the cohesive failure of the adhesive was visually observed after being peeled off in this adhesive strength test, no cohesive failure of the adhesive was observed. These results are shown in Table 2.

Salt Comparison I Uni An adhesive solution was prepared in the same manner as in Example 1 (1-1). An adhesive plaster was prepared and a patch was prepared in the same manner as in Example 1 (1-2) and (1-3) except that no reinforcing filler was added to this adhesive solution. . This patch was subjected to an adhesion test in the same manner as in Example 1 (1-4). As a result, the adhesive plaster exuded around the test piece by an average of 3 mm at the application site on the human body. Furthermore, after the test piece was peeled off, the adhesive plaster remained on the human skin, resulting in stains.

Further, a drug release test was conducted on this patch using the same method as in Example 1 (1-5). The percentage of drug released was 48%. The results are shown in Table 1.

Furthermore, the holding force value (H) and adhesion force value (F) of the adhesive layer of this patch were measured using the same methods as in Example 1 (1-6) and (1-7), respectively. The value of H/F was calculated. The holding force value was 59 (seconds), the adhesive force value was 390 to 780 (g/25+++n+), and the H/F was 0.15 seconds/g. The reason for the observed variation in adhesive force values is the tendency for cohesive failure of the adhesive layer. Further, when the cohesive failure state of the adhesive after being peeled off in this adhesive force test was visually observed, a slight tendency for cohesive failure of the adhesive was observed. These results are shown in Table 2.

A 30% cyclohexane solution was prepared by adding the following compounds to cyclohexane and stirring and mixing as an adhesive composition with a salt-free Tg exceeding 171°C.

Natural rubber (Bale crepe) 100 parts by weight Poly-β-pinene resin (softening point 100°C) 80 parts by weight = 26 Squalane 10 parts by weight 2.6
- D-t-amylhydroquinone 1.5 parts by weight This adhesive solution was used, except that the amount of acetylsalicylic acid as a drug added to this solution was 12 parts by weight per 100 parts by weight of the adhesive component in the solution. In the same manner as in Example 1, an adhesive paste was prepared and a patch was produced. For this patch, the (
An adhesion test was conducted in the same manner as in 1-4). As a result, the periphery of the test piece rose by about 1 mm at the point where it was applied on the human body, indicating that the adhesive did not fully adapt to the skin. When this test piece was peeled off, sufficient adhesive force was not felt on the human body.

In addition, a drug release test was conducted on this patch using the same method as in Example 1 (1-5>).The ratio of the released drug amount was 32%.The results are shown in Table 1. show.

Furthermore, the holding force value (H) and adhesive force value (F) of the adhesive layer of this patch were measured by the same method as in Example 1 (I6) and (1-7), respectively. The value of H/F was calculated. The holding force value was 641 (seconds), the adhesive force value was 433 (g/25mm), and the H/F was 1.48 seconds/g. In addition, when the cohesive failure of the adhesive was visually observed after being peeled off in this adhesive strength test, no cohesive failure of the adhesive was observed. These results are shown in Table 2.

Rubber elastic polyisobutylene (molecular ffi: 106 or more, Vistanex MML-100; manufactured by Exxon) 35
Parts by weight Styrene-isoprene-styrene block copolymer (EX-2359; manufactured by Sumira Chemical Co., Ltd.) 5 parts by weight Liquid polybutene (Molecular It: 1000 or less, Opanol B-1; manufactured by BASF) 60 parts by weight Liquid paraffin 10 parts by weight Part 2.6-Gt
-Butyl-p-cresol (anti-aging agent) 15 parts by weight The above formulation was added to cyclohexane and mixed with stirring to prepare a 50% cyclohexane solution. The Tg (after drying) of the resulting adhesive solution was 881°C.

2-2 -,' To the adhesive solution obtained in (2-1), polypropylene short fibers (average fiber diameter: 11 μm, average fiber length) were added as a reinforcing filler per 100 parts by weight of the adhesive component in the solution. ;15
A sticky paste was prepared by adding 25 parts by weight of 20 mm) and prednisolone (anti-inflammatory agent) 3 as a drug and ONN Koribe and stirring and mixing.

2-3.1 15 μm thick PET (polyethylene terephthalate) film and 35 μm thick EVA (ethylene-terephthalate) film
EV of laminate film of (hinyl acetate copolymer) film
The adhesive paste obtained in (2-2) was applied and transferred onto the A side surface by a transfer method using silicone release paper so that the thickness after drying was 40 μm. Thereby, a patch having an adhesive layer on the laminate film was produced.

2-4It--Egg - Patch Adhesiveness Test 9 was conducted in the same manner as in Example 1, except that the patch obtained in the live test (2-3) was used. As a result, a maximum of approximately 2 mm at the periphery of the test piece
Although some oozing of the adhesive plaster was observed, no natural peeling was observed. When this test piece was peeled off from one end, it felt like a moderate peeling feeling (adhesion) to the human body.
I felt no pain. Furthermore, no adhesive plaster remained on the human skin after the test piece was peeled off.

A circular test piece with a diameter of 60 mm was punched out from the patch obtained in 2-5 (2-3). The releasable sheet was peeled off from this test piece, and a mixed solvent of ethyl alcohol and water (weight ratio;
70: 30) 100ml was allowed to stand and soak at 35°C for 6 hours. Thereafter, the test piece was taken out from the mixed solvent, and the amount of drug extracted into the solvent was determined by liquid chromatography. Ratio (%) of the amount of drug released to the amount of drug calculated to be contained in the test piece
was used to evaluate the drug release properties of the adhesive. The percentage of drug amount released was 88%. These results are shown in Table 1.

30 The holding force value (H) of the adhesive layer was measured in the same manner as in Example 1, except that the patch obtained in (2-3) of 2-6 was used. The holding force value was 226 (seconds).

The adhesive force value (H) of the adhesive layer was measured in the same manner as in Example 1, except that the patch obtained in 2-7 (2-3) was used. The adhesive force value was 462 (g725mm>).

The value of H/F was calculated based on the holding force value (H) and adhesive force value (F) obtained in the holding force test (2-7) and this adhesive force test, respectively. H/F is 0.49 seconds/g
Met. In addition, when the cohesive failure of the adhesive was visually observed after being peeled off in this adhesive strength test, no cohesive failure of the adhesive was observed. These results are shown in Table 2.

An adhesive solution was prepared in the same manner as in Example 2 (2-1). An adhesive plaster was prepared in the same manner as in Example 2 (2-2) and (2-3), except that no reinforcing filler was added to this adhesive solution, and adhesive patch 31- Created. For this patch, (l-4) of Example 1
An adhesion test was conducted in the same manner as above. the result,
The test piece was misaligned by about 8 inches at the point where it was applied on the human body, and adhesive plaster remained in the misplaced area. Furthermore, a stringing phenomenon occurred when the test piece was peeled off, and a thin adhesive paste remained on the human skin after the test piece was peeled off, resulting in stains.

Further, a drug release test was conducted on this patch using the same method as in Example 1 (1-5). The percentage of drug amount released was 92%. The results are shown in Table 1.

Furthermore, the holding force value (H) and adhesion force value (F) of the adhesive layer of this patch were measured using the same methods as in Example 1 (1-6) and (1-7), respectively. The value of H/F was calculated. The holding force value was 91 (seconds), the adhesive force value was 507 (g/25mm), and the H/F was 0.18 seconds/g. In addition, when the cohesive failure state of the adhesive was visually observed after being peeled off in this adhesive force test, the cohesive failure of the adhesive was barely noticeable. These results are shown in Table 2.

As the adhesive having a Tg exceeding -71'C, an acrylic polymer adhesive prepared by polymerizing the following compound was used.

2-Ethylhexyl acrylate 70 parts by weight Vinyl acetate 25 parts by weight Methacrylic acid 5 parts A 30% solution of ethyl acetate with the above formulation was charged into a reaction vessel, heated at 60°C for 10 hours, and then heated to the reflux temperature of the system (74-75°C). Each reaction was polymerized for 14 hours.

In the reaction vessel, 0.5% by weight of lauroyl peroxide based on the total amount of the above monomers was added as a polymerization catalyst in 8 portions, 18
Added within hours.

An adhesive plaster was prepared and a patch was produced in the same manner as in Example 2, except that this adhesive was used. This patch was subjected to an adhesion test in the same manner as in Example 1 (1-4). As a result, at the application site on the human body, the portion where the test piece rose from the skin (that is, the peeled portion) reached approximately 25% of the area of the entire test piece 33-. In addition, when this test piece was peeled off, the human body did not feel sufficient adhesive force.
Low familiarity and adhesion to the skin were observed. However, no adhesive plaster remained on the human skin after the test piece was peeled off.

Further, a drug release test was conducted on this patch using the same method as in Example 1 (1-5). The percentage of drug amount released was 14%. The results are shown in Table 1.

Furthermore, the holding force value (H) and adhesive force value (F) of the adhesive layer of this patch were measured and monitored using the same method as in Example 1 (1-6> and (1-7)). The holding force value was 247 (seconds) and the adhesive force value was 412 (g/25mm).
was 0.6 seconds/g. In addition, when the cohesive failure of the adhesive was visually observed after being peeled off in this adhesive strength test, no cohesive failure of the adhesive was observed. These results are shown in Table 2.

=34- Rubber elastic polyvinyl inbutyl ether (manufactured by Lutonal lcHBASP) 40 parts by weight Liquid polyvinyl isobutyl ether (Lutonal T-30 manufactured by HBASF) 6
0 parts by weight BPBG (plasticizer)
A 45% ethyl acetate solution was prepared by adding 20 parts by weight of the above formulation to ethyl acetate and stirring and mixing.

Here, the rubber component and resin component were cut or crushed to a suitable size or less before use.

The Tg (after drying) of the resulting adhesive solution was -78°C.

3-2 -,1 To the adhesive solution obtained in (3-1), short glass fibers (average diameter: 8 to 10 μm 1 average fiber length) were added as a reinforcing filler per 100 parts by weight of the adhesive component in the solution. ;12-15
A sticky paste was prepared by adding 20 parts by weight of 2-nitric acid insorbitol (coronary vasodilator) and 14 parts by weight of 2-nitric acid insorbitol (coronary vasodilator) as a drug and stirring and mixing.

3-3 affixed/marked 1 5- On the EVA surface of the same laminate film as in Example 2, (3
The adhesive paste obtained in -2) was applied and transferred in the same manner as in Example 2 so that the average thickness after drying was 60 μm. Thereby, a patch having an adhesive layer on the laminate film was produced.

3-4> Patch/Mark R'/Raw Test A patch adhesion test was conducted in the same manner as in Example 1, except that the patch obtained in (3-3) was used. As a result, although oozing of the adhesive plaster up to about 2 mm was observed at the periphery of the test piece, no natural peeling was observed at all. When this test piece was peeled off from one end, the human body felt only a moderate peeling sensation (adhesion) and no pain was felt. Furthermore, no adhesive plaster remained on the human skin after the test piece was peeled off.

Using the patch obtained in the release test (2-3) of Section 3-5, the drug release properties of the patch were tested in the same manner as in Example 1.

As a result, the percentage of released drug amount was 79% and 6 It was. These results are shown in Table 1.

3-6, The holding force value (H) of the adhesive layer was measured in the same manner as in Example 1, except that the patch obtained in (3-3) was used.The holding force value was 651. (seconds).

The adhesive force value (H) of the adhesive layer was measured in the same manner as in Example 1, except that the patch obtained in Test (3-3) marked with 3-7 was used. The adhesive force value was 529 (g/25 mm).

The value of H/F was calculated based on the holding force value (H) and adhesive force value (F) obtained in the holding force test (3-7) and this adhesive force test, respectively. H/F was 1.23. In addition, when the cohesive failure of the adhesive was visually observed after being peeled off in this adhesive strength test, no cohesive failure of the adhesive was observed. These results are shown in Table 2.

Prepare an adhesive solution in the same manner as in Example 3 (3-1).1. Ta. (3-2) and (3-3) of Example 3 except that the reinforcing filler was added to this adhesive solution.
) An adhesive plaster was prepared and a patch was produced in the same manner as in 7. This patch was subjected to an adhesion test in the same manner as in Example 1 (1-4). As a result, at the application site on the human body, the oozing of the adhesive plaster around the test piece was 3 mm on average, and 5 mm in the direction. In addition, the position of the test piece was shifted due to misalignment. After the test piece was peeled off, the adhesive plaster remained on the human skin, resulting in a stain.

Further, a drug release test was conducted on this patch using the same method as in Example 1 (i-s). The percentage of drug amount released was 81%. The results are shown in Table 1.

Furthermore, the holding force value (H) and adhesion force value (F) of the adhesive layer of this patch were measured using the same methods as in Example 1 (16) and (1-7), respectively. H
/F value was calculated. Although the holding force value was 21 (seconds), the adhesive force value could not be measured due to cohesive failure of the adhesive. As a result, H/F is estimated to be less than O1. In addition, when the cohesive failure of the adhesive was visually observed after being peeled off in this 8-adhesion test, the cohesive failure of the adhesive was significant. These results are shown in Table 2.

An adhesive plaster was prepared in the same manner as in Example 1, except that an adhesive with the following composition was used as the adhesive with a Tg exceeding 171°C. Created.

Lutonal IC 60 parts by weight Lutonal I-30 40 parts by weight The adhesive composition according to the above composition was a 30% ethyl acetate solution. (Tg of the solid content: = 33°C) An adhesion test was conducted on this adhesive patch in the same manner as in Example 1 (1-4). As a result, the adhesive paste oozed out around the test piece at the application site on the human body, which was about 1 mm on average, but there were about 4 areas where the test piece rose from the skin (i.e., A peeled part) was visible. In addition, after peeling off this test piece, while a stringing phenomenon occurred,
Adhesive paste remains on the skin surface of the human body and becomes dirty.
- There was.

Further, a drug release test was conducted on this patch using the same method as in Example 1 (1-5). The percentage of drug amount released was 53%. The results are shown in Table 1.

Furthermore, for this patch, the holding force value (H) and adhesive force value (F) of the adhesive layer were measured and monitored using the same method as in Example 1 (1-6) and (t-7). The value of H/F was calculated. The holding force value was 109 (seconds), the adhesive force value was 390-1560 (g/25 mm), and the H/F was 0.28. The reason for the observed variation in adhesive force values is the tendency for cohesive failure of the adhesive layer. In addition, when the cohesive failure state of the adhesive was visually observed after being peeled off in this adhesive force test, a slight tendency for cohesive failure of the adhesive was observed. These results are shown in Table 2.

Liquid polybutadiene containing hydroxyl groups at both ends (polybd R-45D; manufactured by Idemitsu Petrochemical Co., Ltd.) 4
0- (Component A) 94 parts by weight Polyfunctional (2 to 2.5 functional) N at positions including both ends
Liquid polybutadiene (polybd) containing GO groups
HTP-9; manufactured by Idemitsu Petrochemical Co., Ltd. H component B) 6 parts by weight dibutyltin acetate (crosslinking catalyst H component C) o,
oos parts by weight or less of a reinforcing filler mixture (component D) 25 parts by weight 10 parts by weight of finely ground alumina with an average particle size of 5 μm or less, 10 parts by weight of polyvinyl chloride with an average particle size of 5 μm or less, based on an average particle size of 5 μm 10 weight of the following finely ground zinc oxide Among the above formulations, component A and component D, and component B and component C are mixed in advance. Both mixtures are mixed through a mixing head approximately 30 minutes before coating on the siliconized release paper in the following adhesive sheet preparation process. The Tg of this adhesive after crosslinking reaction (curing) was about -78°C.

41-4-2 Sheet 1: Apply the mixture of recipe (4-1) on the surface of silicone release paper whose surface has been smoothed with polylaminate to a thickness of about 100 mm.
A pressure-sensitive adhesive layer was formed by coating to a thickness of μm. After cooling the coated release paper through a curing zone at 100°C for about 1 minute, an adhesive layer is laminated and pressure-bonded on the surface of the soft vinyl chloride film, and 3
An adhesive sheet with a sandwich structure of layers was prepared. This adhesive sheet can be made by peeling off the silicone release paper.
Used for pasting. This adhesive sheet is made into a patch by first peeling off the silicone release paper, coating or spraying the drug itself or its solution on the surface of the adhesive layer, and then attaching the silicone release paper again.

4-3 Sheet, except that the adhesive sheet obtained in (4-2) was used.
The adhesion test of the pressure-sensitive adhesive sheet was conducted in the same manner as in Example 1. As a result, although oozing of the adhesive within 3 mm was observed at the periphery of the test piece, no natural peeling was observed. When this test piece was peeled off from one end, although the adhesive was slightly stretched, it recovered elastically and no adhesive remained on the human skin.

Except for using the adhesive sheet obtained in 4-4 (4-2),
In the same manner as in Example 1, the holding force value (H) of the adhesive layer was measured. The holding force value was 370 (seconds).

4-5 = [The adhesive force value (H) of the adhesive layer was measured in the same manner as in Example 1 except that the adhesive sheet obtained in (4-2) was used. The adhesive force value was 421 (g/25mm).

The value of H/F was calculated based on the holding force value (H) and adhesive force value (F) obtained in the holding force test (4-4) and this adhesive force test, respectively. H/F was 0.88. In addition, when the cohesive failure of the adhesive was visually observed after being peeled off in this adhesive strength test, no cohesive failure of the adhesive was observed. These results are shown in Table 2.

Salt Mosquito Plate Work 3 - Same as in Example 4 except that no reinforcing filler was added.
4-1> and (4-2), an adhesive solution was prepared and an adhesive sheet was produced. This pressure-sensitive adhesive sheet was subjected to an adhesion test in the same manner as in Example 1 (1-4). As a result, oozing of the adhesive within an average of about 4 mm was observed at the periphery of the test piece. Furthermore, when the test piece was peeled off, a long stringing phenomenon occurred, and after the test piece was peeled off, a total amount of about 173% of the adhesive remained on the human skin.

Furthermore, regarding this adhesive sheet, (1-6
) and (1-7), the holding force value (H) and adhesive force value (F) of the adhesive layer were measured, respectively, and the value of H/F was calculated. The holding force value was 123 (seconds), the adhesive force value was 559 (g/25 mm), and the H/F was 0.22. When the cohesive failure state of the adhesive was visually observed, no cohesive failure of the adhesive was observed.These results are shown in Table 2.

(Margin below) 4 5 Table 2 “Cohesive failure (for Koromaki, Adhesion values vary.

6. As is clear from the Examples and Comparative Examples, the patch of the present invention contains a reinforcing fibrous filler in the adhesive layer, so
Excellent balance of adhesiveness and cohesiveness. This means that
The adhesive force value (F) of the patch is 2°08 or more, and
Ratio of holding force value (H) and adhesive force value (F): H/F>0.3
This is proven because it is sec/g. Therefore, no stringing phenomenon or adhesive residue on the skin was observed even in the finger pressure adhesion/repeel test of the adhesive. Furthermore, even when this patch is applied to the human body, there is little oozing of the adhesive. Moreover, no adhesive remains on the human skin after the patch is peeled off. The patch of the present invention further has a glass transition temperature (Tg)
Since the adhesive layer is composed of an adhesive whose temperature is -71℃ or less,
A large amount of drug can be contained in the adhesive layer, and the drug has excellent release properties.

A patch that does not contain a reinforcing filler in the adhesive layer has a poor balance between adhesiveness and cohesiveness, and although its adhesive strength is 200 g or more, the retention strength (H) and adhesive strength (F) are Ratio: H/F≦0.3 seconds/g. Therefore, when this patch is applied to the human body, the adhesive oozes out around the patch, causing the patch to shift significantly. Furthermore, after the patch is peeled off, the adhesive remains on the human skin and becomes a stain. A patch whose adhesive layer is made of an adhesive whose glass transition temperature (Tg) exceeds -71°C cannot contain a large amount of drug in the adhesive layer. Furthermore, the release properties of the drug from the adhesive layer are also poor. In addition, this adhesive patch has poor adhesion because it is poorly compatible with the skin. Therefore, when this patch is applied, a lifting phenomenon (i.e.,
peeling) occurs.

(Effects of the Invention) As described above, the adhesive patch of the present invention uses a novel acrylic acid ester polymer with a glass transition temperature (Tg) of -71°C or less as an adhesive, so the adhesive layer is A large amount of drug is dissolved and drug release is also high. Moreover, since this adhesive patch contains a reinforcing filler in the adhesive layer, it has an excellent balance between adhesiveness and cohesiveness. Therefore, if this patch is used, the efficacy of the drug will be increased and the utilization efficiency of the drug will be increased. It is also economical because a large amount of drug can be contained in one patch. Furthermore, even when this patch is applied to the skin of a human body, there is little oozing of the adhesive or slippage of the patch. The patch will not slip even if the skin stretches and shrinks. The human body does not feel pain when the patch is removed from the skin. No adhesive remains on the skin after the patch is removed. Therefore, with this patch, the patient will not feel any pain or discomfort. By combining the Tg value of the adhesive in the patch and the reinforcing filler, the selection range of substances used as the material for the adhesive can be expanded.

that's all

Claims (1)

[Scope of Claims] 1. A patch having a backing support layer and an adhesive layer, the adhesive layer comprising: an adhesive having a glass transition temperature (Tg) of -71°C or less; a reinforcing filler; and a drug, the adhesive is mainly composed of a non-acrylic compound, and the holding force value (H) and adhesive force value (F) of the adhesive layer satisfy the following relationships of formulas a and b. patch. H/F>0
．． 3 (sec/g)...a F>200(g)...b