JP2014076960A - Hot melt-type adhesive composition and percutaneous absorption patch - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hot melt-type adhesive composition containing a medicament in a high content of the medicament, allowing retention of aggregation power of an adhesive layer and being excellent in coating suitability; and a percutaneous absorption patch comprising an adhesive layer formed from the hot melt-type adhesive composition.SOLUTION: A hot melt-type adhesive composition contains (a) 25 to 50 mass% of a thermoplastic elastomer, (b) 20 to 50 mass% of a tackifier resin, (c) 5 to 9 mass% of a softening agent, (d) 2 to 8 mass% of synthetic aluminum silicate and (e) 10 to 25 mass% of a medicament [where the total of (a) to (e) is 100 mass%]. A percutaneous absorption patch comprises a support and an adhesive layer formed from the hot melt-type adhesive composition.

Description

  The present invention relates to a hot-melt pressure-sensitive adhesive composition and a transdermal absorption patch. Specifically, a hot melt pressure-sensitive adhesive composition that is excellent in coating suitability even when a large amount of drug is blended, and a transdermal skin that includes a support and a pressure-sensitive adhesive layer formed from the hot-melt pressure-sensitive adhesive composition It relates to an absorption patch.

  As a transdermal patch, one having a pressure-sensitive adhesive layer (pressure-sensitive adhesive layer) containing a drug (active ingredient) on a support (lining material) is known. As the pressure-sensitive adhesive forming the pressure-sensitive adhesive layer, an acrylic pressure-sensitive adhesive having features such as low skin irritation is widely used. However, when an acrylic pressure-sensitive adhesive is used, a process for drying the solvent contained in the pressure-sensitive adhesive is required in the production process of the transdermal absorption patch, so that the pressure-sensitive adhesive contains a drug having a low melting point or boiling point. In this case, there is a problem that the drug flows out or volatilizes. Therefore, when obtaining a patch comprising an adhesive layer formed from an adhesive containing a drug having a low melting point or boiling point (for example, methyl salicylate that is liquid at room temperature), a calendar coating that does not require a solvent drying step is required. A rubber-based pressure-sensitive adhesive that can be applied by a construction method or a hot-melt coating method is used.

  In order to avoid latex allergy of natural rubber, and to avoid skin irritation caused by sulfur and other vulcanizing agents and cross-linking agents, rubber adhesives are mainly composed of synthetic rubber-based thermoplastic elastomers. Many rubber adhesives are used. As a synthetic rubber thermoplastic elastomer, as shown in Patent Document 1, a styrene-isoprene-styrene copolymer (hereinafter sometimes referred to as “SIS”), a styrene-butadiene-styrene copolymer (hereinafter referred to as “SIS”). Or hydrogenated products thereof, styrene-ethylene-propylene-styrene copolymer (hereinafter sometimes referred to as “SEPS”), styrene-ethylene-butylene-styrene copolymer. Various thermoplastic elastomers such as thermoplastic block copolymers such as polymers (hereinafter sometimes referred to as “SEBS”); ethylene-vinyl acetate copolymers; ethylene-α-olefin copolymers; Yes. Among these, styrenic thermoplastic elastomers that are thermoplastic block copolymers such as SIS, SBS, SEPS, and SEBS are preferably used because of their excellent adhesiveness and cohesion.

  In order to form a pressure-sensitive adhesive layer from a rubber-based pressure-sensitive adhesive by a calendar coating method, first, a material such as a thermoplastic elastomer is softened at a temperature of 100 to 150 ° C. with a pressure kneader and kneaded for 10 to 30 minutes. The temperature is lowered, the drug is added, and the mixture is further kneaded for 5 to 20 minutes to prepare a calendar-type pressure-sensitive adhesive composition in which each component is uniformly dispersed. In addition, the temperature and time at the time of the above kneading are described by way of examples, and are not limited to these ranges. The same applies hereinafter.

  The obtained calender type pressure-sensitive adhesive composition was passed between two rolls controlled at a temperature of 100 to 200 ° C. in a softened state using a calender coating machine, and a release liner (polyester treated with a silicone surface) was obtained. The film is spread on a film or the like to a thickness of 100 to 250 μm. Next, a patch is obtained by laminating a support on the upper surface of the pressure-sensitive adhesive and cutting it into a predetermined shape.

  In order to form a pressure-sensitive adhesive layer from a rubber-based pressure-sensitive adhesive by a hot melt coating method, first, a material such as a thermoplastic elastomer is heated at a temperature of 100 to 200 ° C. in a nitrogen atmosphere with a high-speed rotating mixer capable of heating control. And stirring for 20 to 100 minutes to obtain a melt. Thereafter, the drug is added to the melt, and further heated and stirred at a temperature of 100 to 190 ° C. for 2 to 30 minutes to prepare a hot melt pressure-sensitive adhesive composition in which each component is uniformly dispersed. In addition, the temperature and time at the time of stirring are described with reference to examples, and are not limited to these ranges.

  The obtained hot-melt pressure-sensitive adhesive composition was extruded with a hot-melt coating machine from a die head part whose temperature was controlled to 100 to 200 ° C., and spread on the release liner to a thickness of 100 to 250 μm. To do. Next, a patch is obtained by laminating a support on the upper surface of the pressure-sensitive adhesive and cutting it into a predetermined shape.

  As described above, the calendar coating method and the hot melt coating method do not require a solvent drying process, but the rubber adhesive is softened or the melt is spread on the release liner. Therefore, in order to obtain good coating suitability, it is required to strictly control the viscosity of the pressure-sensitive adhesive composition at the time of spreading within the optimum range. Especially for hot melt adhesive compositions that perform hot melt coating, unlike the calender coating method, the pressure applied to the adhesive composition during coating is small, so the viscosity of the adhesive composition during spreading is optimal. In order to make it within the range, the pressure-sensitive adhesive composition may be prepared at a higher temperature or the composition may need to be adjusted.

In addition to the above-mentioned thermoplastic elastomers such as SIS, the hot melt adhesive composition is often an aliphatic petroleum resin, aromatic petroleum resin, rosin resin, terpene resin, coumarone indene resin. Containing a softening agent such as a tackifier resin (also referred to as “tackifier resin”), a polyester plasticizer, a naphthenic oil, an aromatic oil, a paraffinic oil, etc., and SiO ₂ , Non-expandable inorganic hollow particles such as Al ₂ O ₃ glass balloons, silica balloons, and shirasu balloons, inorganic fillers such as calcium carbonate and talc; anti-aging agents such as bisphenol-based and triazine-based antioxidants; ultraviolet rays Absorbent; may contain a crosslinking agent or the like (see Patent Documents 2 and 3).

  The hot melt pressure-sensitive adhesive composition for forming a transdermal absorption patch further contains a drug (hereinafter sometimes referred to as “pharmacologically active substance”), and further contains a transdermal absorption enhancer and the like. May be. Examples of drugs include autonomic nervous system agonists, somatic nervous system agonists, central nervous system agonists, sympathomimetic drugs, sympathetic nerve blockers, parasympathomimetic drug drugs, parasympathetic nerve blockers, local anesthetics, systemic drugs Anesthetics, smooth muscle agonists, smooth muscle relaxants, non-steroidal anti-inflammatory drugs, steroidal anti-inflammatory drugs, anti-asthmatic drugs, uterine contractors, analgesics / hypnotics, antidepressants, anti-gout drugs, antihistamines , Antiallergic drugs, antiserotonin drugs, cardiovascular drugs, cardiovascular drugs, antiarrhythmic drugs, antihyperlipidemic drugs, diuretics, respiratory system drugs, digestive system drugs, blood and hematopoietic organ drugs , Skin / mucosal agents, imidazole antifungal agents, hormones, vitamins, anti-infective agents, antineoplastic agents, antidiabetic agents, antiemetics, and the like.

  The hot-melt pressure-sensitive adhesive composition containing a drug changes adhesive properties, cohesiveness, drug bleedability, and the like depending on the composition. Conventionally, in hot-melt pressure-sensitive adhesive compositions, the blending ratio of blending components other than thermoplastic elastomers, such as tackifier resins and softeners, tends to increase, and as a result, the temperature dependence of the adhesive properties increases. Therefore, there is a problem that the practical temperature range is narrowed, or the cohesive force is too high, and when the patch is peeled off from the application site, the application site is required to have removability, such as damaging the application site or cutting the patch There was a problem that was not suitable for.

  For example, the softening agent is blended in order to improve the low temperature characteristics, to lower the melt viscosity of the pressure-sensitive adhesive composition to increase fluidity, and to improve coating properties. However, when the amount of the softening agent is increased in order to improve the low temperature characteristics, the cohesive force, particularly the cohesive force at high temperature, is inferior and the creep resistance tends to be deteriorated. Moreover, when the melt viscosity at the time of coating is too small, a pressure-sensitive adhesive layer having a predetermined thickness may not be formed. Therefore, in order to maintain the cohesive strength of the pressure-sensitive adhesive layer, it is desired that the content of the softening agent in the pressure-sensitive adhesive composition is less than 10% by mass, preferably 9% by mass or less.

  On the other hand, in recent years, a hot-melt adhesive composition containing a drug used for forming a transdermal absorption patch has been used in order to obtain a long-lasting pharmacological activity and, if desired, a transdermal absorption patch. In order to reduce the sticking area, it may be desired to increase the content of the drug in the adhesive composition, specifically, to set the content of the drug to 10% by mass or more. In addition, in order to provide a cooling sensation effect, it may be desired to increase the content of low melting point drugs such as drugs that are liquid at room temperature. In the transdermal patch, in order to obtain a pressure-sensitive adhesive layer formed from a hot-melt pressure-sensitive adhesive composition, as described above, a material such as a thermoplastic elastomer is heated to form a melt, and the melt The product may further contain a drug, and a composition for a hot-melt pressure-sensitive adhesive containing a drug in a molten state may be extruded and spread on the release liner. When applying a composition for a hot melt adhesive that is a melt, an adhesive layer having a uniform thickness in as short a time as possible to prevent the outflow and volatilization of drugs, particularly low melting point drugs. Application suitability capable of forming a film is required. Specifically, coating suitability is required in which the melt viscosity of the pressure-sensitive adhesive composition is within an appropriate range under the coating conditions of the hot-melt pressure-sensitive adhesive composition containing a drug.

  From these circumstances, a hot-melt pressure-sensitive adhesive composition containing a drug whose content is as high as 10% by mass or more, which retains the cohesive strength of the pressure-sensitive adhesive layer and is suitable for coating. There has been a demand for an excellent hot-melt pressure-sensitive adhesive composition and a transdermal absorption patch comprising a pressure-sensitive adhesive layer formed from the hot-melt pressure-sensitive adhesive composition.

Japanese Examined Patent Publication 45-41518 JP-A-7-179836 JP-A-11-106730

  An object of the present invention is a hot melt pressure-sensitive adhesive composition containing a drug having a high drug content, which can maintain the cohesive strength of the pressure-sensitive adhesive layer and is excellent in coating suitability An object of the present invention is to provide a transdermal absorption patch comprising a composition and a pressure-sensitive adhesive layer formed from a hot-melt pressure-sensitive adhesive composition.

  As a result of diligent research on solving the above-mentioned problems, the present inventors have found that in a hot melt pressure-sensitive adhesive composition containing a predetermined amount of a thermoplastic elastomer, a tackifier resin, a softener and a drug, synthetic aluminum silicate is used. It has been found that the problem can be solved by containing a predetermined amount, and the invention has been completed.

That is, according to the present invention, the following components (a) to (e):
(A) Thermoplastic elastomer 25-50 mass%,
(B) Tackifying resin 20-50% by mass,
(C) Softener 5-9% by mass,
(D) Synthetic aluminum silicate 2-8% by mass and (e) Drug 10-25% by mass
[However, the sum of (a) to (e) is 100% by mass. ]
A hot melt pressure-sensitive adhesive composition is provided.

  Moreover, according to this invention, the hot-melt-type adhesive composition of the following (1)-(4) is provided as an aspect.

(1) The hot melt pressure-sensitive adhesive composition, wherein the thermoplastic elastomer (a) contains a styrenic thermoplastic elastomer and the drug (e) contains a drug that is liquid at room temperature. .

(2) The hot-melt pressure-sensitive adhesive composition, wherein the (b) tackifying resin contains a rosin resin, and the (c) softening agent is a naphthenic or paraffinic oil.

(3) The hot melt pressure-sensitive adhesive composition as described above, wherein (d) the synthetic aluminum silicate is light synthetic aluminum silicate.

(4) The said hot-melt-type adhesive composition obtained from the composition whose melt viscosity in 150 degreeC temperature is 250 dPa * s or less.

Moreover, according to this invention, a transdermal patch provided with a support body and the adhesive layer formed from the said hot-melt-type adhesive composition is provided. As an embodiment thereof, the transdermal absorption patch, wherein the support is a fiber substrate, is provided, and the transdermal absorption patch further comprising a release sheet is provided. The above-mentioned transdermal absorption patch, wherein the surface area of the agent layer is 4 to ²⁰ cm ² is provided.

According to the invention, the following components (a) to (e):
(A) Thermoplastic elastomer 25-50 mass%,
(B) Tackifying resin 20-50% by mass,
(C) Softener 5-9% by mass,
(D) Synthetic aluminum silicate 2-8% by mass and (e) Drug 10-25% by mass
[However, the sum of (a) to (e) is 100% by mass. ]
Is a hot melt pressure-sensitive adhesive composition having a high drug content, and can maintain the cohesive strength of the pressure-sensitive adhesive layer. The effect of being able to provide a transdermal absorption patch comprising a hot melt pressure-sensitive adhesive composition excellent in coating suitability, a support, and a pressure-sensitive adhesive layer formed from the hot-melt pressure-sensitive adhesive composition. Play.

The hot melt pressure-sensitive adhesive composition of the present invention includes the following components (a) to (e):
(A) Thermoplastic elastomer 25-50 mass%,
(B) Tackifying resin 20-50% by mass,
(C) Softener 5-9% by mass,
(D) Synthetic aluminum silicate 2-8% by mass and (e) Drug 10-25% by mass
[However, the sum of (a) to (e) is 100% by mass. ]
It is a hot-melt-type adhesive composition characterized by containing.

1. Thermoplastic Elastomer As the thermoplastic elastomer (a) contained in the hot-melt pressure-sensitive adhesive composition of the present invention, a thermoplastic elastomer conventionally contained in a hot-melt pressure-sensitive adhesive composition can be employed. That is, various thermoplastic elastomers such as the above-described SIS, SBS, or their hydrogenated products, thermoplastic block copolymers such as SEPS, SEBS; ethylene-vinyl acetate copolymer; ethylene-α-olefin copolymer; Can be used. Among these, styrenic thermoplastic elastomers that are styrenic block copolymers such as SIS, SBS, SEPS, and SEBS are preferred because of their excellent adhesiveness and cohesiveness.

  These thermoplastic elastomers such as styrenic thermoplastic elastomers may be used alone or as a mixture of two or more. Further, as long as the effects of the present invention can be obtained, other rubber-like polymers and elastomers such as natural rubber; butyl rubber, isobutylene rubber, isoprene rubber and the like, together with the thermoplastic elastomer such as the styrene-based thermoplastic elastomer described above. A synthetic rubber; a polybutadiene-based (co) polymer; a hydrogenated product thereof; or a mixture of two or more of these may be used in combination.

  The styrenic block copolymer, which is a styrenic thermoplastic elastomer preferably used, is generally represented by AB type or ABA type (A is a single aromatic vinyl such as styrene). B represents a polymer block of a conjugated diene monomer such as isoprene or butadiene.) A block copolymer.

  As the aromatic vinyl monomer, styrene, α-methylstyrene, p-methylstyrene, m-methylstyrene, o-methylstyrene, p-tert-butylstyrene, dimethylstyrene, vinylnaphthalene, and the like can be used. Styrene is preferred. Further, as the conjugated diene monomer, butadiene, isoprene, piperylene and the like can be used, and butadiene and isoprene are preferable.

  The styrene block copolymer has an aromatic vinyl portion of 5 to 45% by mass, preferably 10 to 30% by mass. When the aromatic vinyl part is less than 5% by mass, the cohesive force is lowered, and when it exceeds 45% by mass, the flexibility is lowered. The weight average molecular weight of the styrenic block copolymer is preferably 10,000 to 400,000, more preferably 50,000 to 250,000.

  Examples of such a styrene block copolymer include AB type, styrene-isoprene copolymer (SI), styrene-butadiene copolymer (SB), and ABA type, styrene-isoprene- Styrene block copolymer (SIS), styrene-butadiene-styrene block copolymer (SBS) and hydrogenated products thereof, styrene-ethylene-propylene-styrene block copolymer (SEPS), styrene-ethylene-butylene-styrene Mention may be made of thermoplastic elastomers such as block copolymers (SEBS).

  Styrenic thermoplastic elastomers preferably used include: JSR SIS manufactured by JSR Corporation; QUINTAC (registered trademark) manufactured by ZEON Corporation; Clayton (registered trademark) manufactured by Kraton Polymers, Califlex (registered trademark) TR; commercially available products such as Taffeprene (registered trademark), Asaprene (registered trademark) T manufactured by Asahi Kasei Chemicals Corporation; Denka (registered trademark) STR manufactured by Denki Kagaku Kogyo Co., Ltd. can be used.

  In the hot melt pressure-sensitive adhesive composition of the present invention, the content of the thermoplastic elastomer (a) is 25 to 50% by mass, preferably 27 to 47% by mass, more preferably 30 to 45% by mass, Preferably it is the range of 32-42 mass%. (A) When the content of the thermoplastic elastomer is less than 25% by mass or more than 50% by mass, hot melt coating without using a solvent may be difficult.

2. Tackifying resin As the (b) tackifying resin contained in the hot-melt pressure-sensitive adhesive composition of the present invention, a tackifying resin conventionally contained in a hot-melt pressure-sensitive adhesive composition can be employed. That is, (b) tackifying resins include natural products such as rosin resins and terpene resins and derivatives thereof, aliphatic petroleum resins, alicyclic petroleum resins, aromatic petroleum resins, coumarone indene resins And synthetic resins such as styrene resins, phenol resins, and xylene resins. Petroleum resins can be classified into synthetic petroleum resin (C5) series and synthetic petroleum resin (C9) series. (B) By containing tackifying resin, the self-adhesive force and adhesive force in normal temperature can be provided to an adhesive component.

  Examples of rosin resins include pine crystals and ester gums manufactured by Arakawa Chemical Co., Ltd .; Polypel Resin, Stevelite Resin, Foral AX, Pentaline (registered trademark) manufactured by Eastman Chemical Co., Ltd .; Harrier Star manufactured by Harima Chemicals Co., Ltd. (Registered trademark) T; Examples of the rosin phenol resin include Tamanol (registered trademark) manufactured by Arakawa Chemical Industries, Ltd .; Sumilite (registered trademark) resin PR manufactured by Sumitomo Durez Co., Ltd., and the like.

  As the terpene resin, YS Resin PX, YS Resin TO, YS Polyster (registered trademark) T manufactured by Yashara Chemical Co., Ltd .; Picolite (registered trademark) A manufactured by Hercules; Is mentioned.

  Examples of the aliphatic petroleum resin include Piccopal (registered trademark) manufactured by Hercules; Escorez manufactured by Tonex; Wing Tack manufactured by Goodyear; Hilets (registered trademark) manufactured by Mitsui Chemicals; Examples include Quinton (registered trademark); Marukaretsu (registered trademark) manufactured by Maruzen Petrochemical Co., Ltd .; Corporex (registered trademark) manufactured by Toho Petroleum Resin Co., Ltd., and the like.

  Examples of the alicyclic petroleum resin include Alcon (registered trademark) P and Alcon M manufactured by Arakawa Chemical Industries, Ltd. Examples of the aromatic petroleum resin include Petrogin manufactured by Mitsui Chemicals, Inc .; High Resin manufactured by Toho Petroleum Resin Co., Ltd. Examples of the coumarone indene resin include Coumarone NG manufactured by Nippon Steel Chemical Co., Ltd.

  Examples of the styrenic resin include Piccolastic (registered trademark) A manufactured by Hercules. Examples of the phenolic resin include hitanol manufactured by Hitachi Chemical Co., Ltd .; tackolol manufactured by Sumitomo Chemical Co., Ltd .; Examples of the xylene-based resin include Nicanol (registered trademark) manufactured by Mitsubishi Gas Chemical Co., Ltd.

  These resins can be used alone or in combination of two or more as (b) a tackifying resin. (B) Content of tackifying resin is 20-50 mass% in a hot-melt-type adhesive composition, Preferably it is 22-47 mass%, More preferably, it is 25-45 mass%, More preferably, it is 27. It is the range of -42 mass%. Moreover, (b) tackifying resin is 10-150 mass parts normally with respect to 100 mass parts of (a) thermoplastic elastomer, Preferably it is 30-140 mass parts, More preferably, it is a ratio of 50-130 mass parts. It may be contained in. (B) If there are too few tackifying resins, the adhesiveness of an adhesive layer will be inferior, and if there are too many (b) tackifying resins, it will become difficult to provide a low-temperature characteristic fall and removability.

3. Softening agent As the softening agent (c) contained in the hot-melt pressure-sensitive adhesive composition of the present invention, a softening agent conventionally contained in a hot-melt pressure-sensitive adhesive composition can be employed. That is, examples of the (c) softener include petroleum softeners, vegetable oil softeners, synthetic plasticizers, liquid rubbers, and liquid tackifier resins. By blending a softening agent, characteristics such as cohesion can be controlled. When the blending ratio of the softening agent is too small, the effect of the addition becomes insufficient, and when it is too large, various properties as a hot-melt pressure-sensitive adhesive composition tend to be lowered.

  Examples of petroleum softeners include paraffinic oil (including liquid paraffin), naphthenic oil, and aromatic oil. Examples of vegetable oil-based softeners include castor oil, cottonseed oil, linseed oil, rapeseed oil, soybean oil, palm oil, coconut oil, peanut oil, tall oil, and the like.

  Examples of the synthetic plasticizer include phthalic acid derivatives such as diethyl phthalate and dibutyl phthalate; isophthalic acid derivatives such as dimethyl isophthalate and diisooctyl phthalate; tetrahydrophthalic acid derivatives such as di- (2-ethylhexyl) tetrahydrophthalate; Adipic acid derivatives such as n-butyl adipate and di- (2-ethylhexyl) adipate; azelaic acid derivatives such as diisooctyl azelate; sebacic acid derivatives such as di-n-butyl sebacate; maleic acid derivatives such as dimethyl malate A fumaric acid derivative such as di-n-butyl fumarate; a trimellitic acid derivative such as triisooctyl trimellitate; a citric acid derivative such as triethyl citrate; an itaconic acid derivative such as diethyl itaconate; a glyceryl monooleate me Acid derivatives; ricinoleic acid derivatives such as butylacetylricinoleate; stearic acid derivatives such as n-butyl stearate; fatty acid derivatives such as diethylene glycol monourarate; sulfonic acid derivatives such as benzenesulfonbutyramide; phosphoric acid such as trimethyl phosphate Derivatives; Monoester plasticizers such as tetra-2-ethylhexyl pyromellate; Glycol derivatives such as diethylene glycol dibenzoate; Glycerin derivatives such as glycerol monoacetate; Paraffin derivatives such as chlorinated paraffin; Epoxy derivatives; Polyester plasticizers; Polyether plasticizers; and the like.

  (C) As the softening agent, a petroleum softening agent is preferably used, and as the paraffinic oil, High Coal (registered trademark) M manufactured by Kaneda Corporation; Lubuflex 100 manufactured by Shell Chemicals Japan Co., Ltd .; Idemitsu Kosan Co., Ltd. Dana process oil PW-90 manufactured by the company, etc., as naphthenic oil, shelf Rex (registered trademark) 371N manufactured by Shell Chemicals Japan Co., Ltd .; Sankyo Process Oil NC-100 manufactured by Sankyo Oil Chemical Co., Ltd .; Japan Examples include aromatic oils such as Sansen-450 manufactured by Sun Oil Co., Ltd., and aromatic oils such as Dutrex (registered trademark) 729UK manufactured by Shell Chemicals Japan Co., Ltd. and Diana Process Oil AC-12 manufactured by Idemitsu Kosan Co., Ltd. Can be mentioned.

  These (c) softeners are selected and used in consideration of compatibility with (a) thermoplastic elastomer and the like, and can be used alone or in combination of two or more. The hot melt pressure-sensitive adhesive composition of the present invention is characterized in that the content of the softening agent (c) is a small amount of 5 to 9% by mass, preferably 5.2 to 8.5% by mass. Preferably it is 5.3-8 mass%, More preferably, it is the range of 5.4-7.5 mass%. Moreover, (c) softener is 10-50 mass parts normally with respect to 100 mass parts of (a) thermoplastic elastomer, Preferably it is 12-45 mass parts, More preferably, it is a ratio of 15-40 mass parts. It may be contained. (C) When the content of the softening agent is less than 5% by mass, the melt viscosity becomes high and the coating property is inferior. When the content exceeds 9% by mass, the creep resistance at high temperature is deteriorated, and the melting during coating The viscosity may be too small.

  The total content of (b) tackifying resin and (c) softener in the hot-melt pressure-sensitive adhesive composition is 20 to 180 parts by mass, preferably 45 to 150 parts by mass with respect to 100 parts by mass of a) thermoplastic elastomer. Part. If it is less than 20 parts by mass, the melt viscosity becomes too high and the coating workability is deteriorated. If it exceeds 180 parts by mass, the low-temperature characteristics are deteriorated, the creep resistance characteristics at high temperatures are deteriorated, or the melting during coating In some cases, the viscosity becomes too small, or re-peelability cannot be imparted.

4). Synthetic aluminum silicate The hot-melt pressure-sensitive adhesive composition of the present invention contains (d) a synthetic aluminum silicate, thereby melting the hot-melt pressure-sensitive adhesive composition to form a pressure-sensitive adhesive layer. The coating suitability is remarkably improved. As a result, i) the coating speed can be increased, the production efficiency can be improved, and the outflow and volatilization of the drug can be reduced. Ii) the melting temperature can be lowered, and the outflow and volatilization of the drug. Iii) The content of the drug present in the pressure-sensitive adhesive layer can be strictly controlled.

(D) the synthetic aluminum silicate contained in the hot melt pressure-sensitive adhesive composition of the present invention,
Formula Al ₂ 0 ₃ · 9SiO ₂ · nH ₂ O
(In the formula, n is a number representing the water content of the compound.)
Natural silicates that are mostly insoluble by adding a sodium hydroxide solution and heating it, leaving it slightly insoluble, as defined in the 16th revision Japanese Pharmacopoeia. It can be distinguished from aluminum silicate and is characterized by fewer impurities and less variation in density and particle size compared to natural aluminum silicate. (D) As the synthetic aluminum silicate, any of special light synthetic aluminum silicate, light synthetic aluminum silicate, or heavy synthetic aluminum silicate classified by apparent specific volume can be used. (D) Particularly preferred as the synthetic aluminum silicate is light synthetic aluminum silicate from the viewpoint of dispersibility and cohesiveness. (D) The synthetic aluminum silicate is preferably a fine powder type having a total particle size distribution of 45 μm or less. The particle size is measured according to the pharmacopoeia general test method “3.04 particle size measurement method”.

  The content of (d) synthetic aluminum silicate in the hot melt pressure-sensitive adhesive composition of the present invention is 2 to 8% by mass, preferably 2.2 to 7.7% by mass, more preferably 2.5. -7.5 mass%, More preferably, it is 2.7-7.3 mass%. (D) As a synthetic aluminum silicate, what is marketed can be used, Kyodo word (trademark) by Kyowa Chemical Industry Co., Ltd., Sankei by Sankei Pharmaceutical Co., Ltd., etc. are used preferably.

5. Drug The hot-melt pressure-sensitive adhesive composition of the present invention contains (e) 10 to 25% by mass of a drug (pharmacologically active substance). (E) The drug is not particularly limited. For example, non-steroidal anti-inflammatory drug, steroidal anti-inflammatory drug, autonomic nervous system drug, somatic nervous system drug, central nervous system drug, sympathomimetic drug Sympathetic blockade, parasympathomimetic, parasympathetic blockade, local anesthetic, general anesthetic, smooth muscle agonist, smooth muscle relaxant, antiasthma, uterine contractor, analgesic / hypnotic, antidepressant , Anti-gout, antihistamine, antiallergic, antiserotonin, cardiovascular, cardiotonic, antiarrhythmic, antihyperlipidemic, diuretic, respiratory, gastrointestinal Drugs, blood / hematopoietic organ acting drugs, skin / mucosal acting drugs, imidazole antifungal drugs, hormones, vitamins, anti-infective drugs, antineoplastic drugs, antidiabetic drugs, antiemetics, and the like.

  The drug (e) contained in and preferably used in the hot melt pressure-sensitive adhesive composition of the present invention is an anti-inflammatory drug, and among them, an anti-inflammatory agent that acts locally to suppress inflammation can be contained. As a component of the anti-inflammatory agent, methyl salicylate, glycol salicylate, felbinac, indomethacin, dl-camphor and the like are preferably used. The transdermal absorption patch comprising an adhesive layer formed from the hot melt adhesive composition of the present invention can be used as an anti-inflammatory patch or a transdermal analgesic / anti-inflammatory agent, and when used as an anti-inflammatory patch Has a stimulating effect such as l-menthol, dl-menthol, dl-camphor, d-camphor, peppermint oil, eucalyptus oil, capsaicin, capsicum extract, nonyl acid vanillylamide, etc. Ingredients can be added. These can be used alone or in combination of two or more. (E) When a drug that is liquid at room temperature, for example, methyl salicylate (melting point: −8 to −7 ° C.) is used as the drug, efficacy and skin irritation are often good. (E) A hot-melt pressure-sensitive adhesive composition having a particularly preferred combination as a drug is a combination of methyl salicylate, dl-camphor, l-menthol and nonyl acid vanillylamide, and (e) a hot-melt pressure-sensitive adhesive containing as a drug A transdermal absorption patch comprising an adhesive layer formed from the composition.

  The hot-melt pressure-sensitive adhesive composition of the present invention has (e) 10 to 25% by mass of the drug (however, the total of (a) to (e) is 100% by mass) in order to improve the effectiveness. ] In large quantities. The content of the drug (e) in the pressure-sensitive adhesive composition is preferably 11 to 24% by mass, more preferably 12 to 23% by mass, and still more preferably 13 to 22% by mass.

6). Other components In addition to the components (a) to (e), the hot melt pressure-sensitive adhesive composition of the present invention can further contain other components as necessary. For example, an ultraviolet absorber, an anti-aging agent (antioxidant), a drug absorption accelerator and the like can be contained, and (d) a filler other than synthetic aluminum silicate can be contained.

  Examples of ultraviolet absorbers include salicylic acid derivatives, benzophenone compounds, benzotriazole compounds, cyanoacrylate compounds, and the like. Although the content rate in the case of using a ultraviolet absorber is not specifically limited, 0.1 to 5 mass parts normally with respect to 100 mass parts of (a) thermoplastic elastomer, Preferably it is 0.2 to 3 mass parts. Preferably it is made to contain in the ratio of 0.5-2 mass parts.

  Anti-aging agents (antioxidants) include naphthylamine compounds, diphenylamine compounds, p-phenylenediamine compounds, other amine compounds, amine compound mixtures, quinoline compounds, hydroquinone derivatives, monophenol compounds, bisphenols. Compounds, trisphenol compounds, polyphenol compounds, thiobisphenol compounds, and the like. Particularly preferably used is di-tert-butylhydroxytoluene (hereinafter sometimes referred to as “BHT”) which is a monophenol compound. Although the content rate of an anti-aging agent is not specifically limited, It is 0.1-5 mass parts normally with respect to 100 mass parts of (a) thermoplastic elastomer, Preferably it is 0.2-3 mass parts, More preferably, it is 0.00. It is a ratio of 5 to 2 parts by mass.

  Examples of drug absorption accelerators include terpene oils such as d-limonene; fatty acid esters such as glycerol monolaurate, glycerol monooleate and diethyl sebacate; fatty acids such as azone, pyrothiodecane, oleic acid, lauric acid and myristic acid; Or the derivative | guide_body etc. are mentioned. Although the content rate of a drug absorption promoter is not specifically limited, (a) It is 0.1-5 mass parts normally with respect to 100 mass parts of thermoplastic elastomers, Preferably it is 0.2-3 mass parts, More preferably, it is 0. .5 to 2 parts by mass.

  (D) As fillers other than synthetic aluminum silicate, for example, calcium carbonate, zinc white (zinc oxide), silica, talc, diatomaceous earth, silica sand, pumice powder, slate powder, mica powder, aluminum sol, alumina White, aluminum sulfate, barium sulfate, lithopone, calcium sulfate, molybdenum disulfide, graphite, glass sphere, single crystal potassium titanate, carbon fiber, activated zinc white, zinc carbonate, magnesium oxide, basic magnesium carbonate, resurge, red lead Lead white, calcium hydroxide, activated calcium hydroxide, titanium oxide and the like. Among these fillers, calcium carbonate, zinc white, silica, titanium oxide and the like are preferably used. When these fillers are blended, the cohesive strength and coating suitability of the pressure-sensitive adhesive layer may be adjusted. The average particle size of the filler is preferably 5 μm or less.

  (D) When using fillers other than a synthetic aluminum silicate, the content is 0.1-150 mass parts normally with respect to 100 mass parts of (a) thermoplastic elastomer components, Preferably it is 1-100. The amount is 3 parts by mass, more preferably 3-60 parts by mass. When the blending ratio of the filler is too large, addition becomes difficult or coating suitability and other physical properties are deteriorated. Needless to say, (d) a filler other than synthetic aluminum silicate may be omitted.

  The hot-melt pressure-sensitive adhesive composition of the present invention further has hydrophilic additives for promoting moisture permeability, such as polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), as long as the adhesive properties and stability over time are not impaired. ), Polycarboxymethylcellulose (CMC), polyethylene glycol (PEG), polypropylene glycol (PPG), diglycerin, polyglycerin, polyacrylate, polyethylene oxide (PEO), polyvinyl butyral, polyoxyethylene nonylphenyl ether, karaya gum, Natural polysaccharides such as pectin can be contained, and one or two or more of these may be used as appropriate. The content is usually 1 to 100 parts by weight, preferably 2 to 70 parts by weight, more preferably 3 to 50 parts by weight, based on 100 parts by weight of the thermoplastic elastomer component (a), but is not blended. There is no problem.

7). Hot-melt type pressure-sensitive adhesive composition The hot-melt type pressure-sensitive adhesive composition of the present invention comprises (a) a thermoplastic elastomer of 25 to 50% by mass, (b) a tackifier resin of 20 to 50% by mass, and (c) a softening agent. 9% by mass, (d) 2 to 8% by mass of synthetic aluminum silicate, and (e) 10 to 25% by mass of drug [provided that the total of (a) to (e) is 100% by mass. ] Is contained. The hot melt pressure-sensitive adhesive composition of the present invention may further contain an anti-aging agent and other components as desired. The hot melt pressure-sensitive adhesive composition of the present invention has (e) a drug content of 10 in order to improve the effectiveness of a transdermal absorption patch comprising a pressure-sensitive adhesive layer formed from the composition and a support. -25% by mass, and (c) 2 to 8% by mass of synthetic aluminum silicate while having a unique composition of 5-9% by mass of softener By doing so, the coating workability when the composition is obtained by hot-melt coating on a support while maintaining the cohesive strength of the pressure-sensitive adhesive layer is good.

  Specifically, the hot melt pressure-sensitive adhesive composition of the present invention has a melt viscosity at a temperature of 150 ° C. of preferably 250 dPa · s or less, more preferably 220 dPa · s or less, and even more preferably 200 dPa · s or less. It is obtained from things. The hot melt pressure-sensitive adhesive composition of the present invention is a composition containing (a) a thermoplastic elastomer, (b) a tackifier resin, (c) a softener, (d) a synthetic aluminum silicate, and (e) a drug. As the melt viscosity is small, the coating suitability is remarkably improved. As a result, i) the coating speed can be increased to form an adhesive layer having a predetermined uniform thickness, and the production efficiency is improved. Can reduce the outflow and volatilization of the drug, ii) can lower the melting temperature, can suppress the volatilization, decomposition and deterioration of the drug, iii) the content of the drug present in the adhesive layer is strictly It is possible to control such as that. On the other hand, if the melt viscosity at the time of application of the hot melt pressure-sensitive adhesive composition is too small, a pressure-sensitive adhesive layer having a predetermined uniform thickness may not be formed. Therefore, the temperature of the hot-melt pressure-sensitive adhesive composition of the present invention It is preferable to adjust the melt viscosity at 150 ° C. so that it is usually 50 dPa · s or more, and in many cases 100 dPa · s or more. In addition, when the drug (e) contained in the hot melt pressure-sensitive adhesive composition of the present invention is a liquid drug at room temperature or a drug that easily volatilizes when heated, (a) to (e) and optionally contained. When a hot melt adhesive composition comprising other ingredients is applied to a hot melt, a part of the drug may be lost, but the melt viscosity before and after the hot melt application is almost unchanged. Absent. The melt viscosity of the hot melt pressure-sensitive adhesive composition is a value measured using a B-type viscometer (measurement conditions are a temperature of 150 ° C., rotor No. 3, 62.5 rpm, 30 seconds).

  The hot-melt pressure-sensitive adhesive composition of the present invention comprises (a) 25 to 50% by mass of a thermoplastic elastomer, (b) 20 to 50% by mass of a tackifier resin, (c) 5 to 9% by mass of a softening agent, and (d). Synthetic aluminum silicate 2 to 8% by mass, and (e) drug 10 to 25% by mass [However, the total of (a) to (e) is 100% by mass. As a preferred composition, the (a) thermoplastic elastomer contains a styrenic thermoplastic elastomer, and the (e) drug is a liquid at room temperature. A hot-melt type pressure-sensitive adhesive composition to be contained is also mentioned. As a preferable composition, the (b) tackifying resin contains a rosin resin, and the (c) softening agent is a naphthenic resin. Or the hot-melt-type adhesive composition which is paraffin type oil is mentioned, The combination of these preferable compositions is an especially preferable hot-melt-type adhesive composition.

8). Method for preparing hot melt pressure-sensitive adhesive composition The method for preparing the hot melt pressure-sensitive adhesive composition of the present invention is not particularly limited. Usually, in a high-speed rotating mixer capable of heating control, (e) material excluding drug, that is, (a) thermoplastic elastomer, (b) tackifying resin, (c) softener, (d) synthetic aluminum silicate And, if necessary, other components contained in the atmosphere or in a nitrogen atmosphere, usually at a temperature of 100 to 200 ° C. for 20 to 120 minutes with heating and stirring to obtain a melt, and (e) a drug in the melt In a nitrogen atmosphere with the atmosphere blocked, the temperature was 100 to 190 ° C., preferably (e) at a lower temperature than before the drug was added, and the mixture was heated and stirred for 2 to 30 minutes to make each component uniform. A composition for a hot melt adhesive is obtained. As described above, the composition for a hot melt pressure-sensitive adhesive has a melt viscosity at a temperature of 150 ° C., preferably 250 dPa · s or less, more preferably 220 dPa · s or less, and further preferably 200 dPa · s or less. . (E) Among drugs added to the melt, for drugs that are liquid at room temperature or highly volatile, the temperature and time conditions during heating and stirring, the hot melt coating conditions described later, etc. The amount may be lost. In that case, an amount of the drug calculated by adding a predetermined amount determined in advance according to the amount of the drug to be lost may be added. The amount of the drug determined by pre-calibration to be added is usually 3 to 25%, in most cases 5 to 22%, most often 8 when the amount of the drug to be contained in the hot melt pressure-sensitive adhesive composition is 100%. -20% (all are based on mass). As mentioned above, since the melt viscosity before and after hot melt coating hardly changes, the “melt viscosity of the composition for hot melt pressure sensitive adhesive” is simply referred to as “hot melt pressure sensitive adhesive composition”. The “melt viscosity of the hot melt pressure-sensitive adhesive” may be simply referred to as “hot-melt pressure-sensitive adhesive composition”. Moreover, the temperature and time at the time of stirring are described with reference to examples, and are not limited to these ranges, but are adjusted according to the composition. (E) When a drug is added and then heated and stirred for a long time, (e) the drug may be decomposed or deteriorated by heat, and in some cases, an amount more than expected may flow out or volatilize. So you need to be careful.

9. Transdermal absorption patch The hot-melt adhesive composition of the present invention is suitable for obtaining a transdermal absorption patch comprising an adhesive layer formed from the hot-melt adhesive composition and a support. is there. That is, according to the present invention, a transdermal patch comprising a support and a pressure-sensitive adhesive layer formed from the hot melt pressure-sensitive adhesive composition of the present invention is provided. The thickness of the transdermal absorption patch is usually 100 to 1000 μm, preferably 200 to 800 μm, more preferably 250 to 600 μm.

[Support]
The support provided in the transdermal absorption patch of the present invention is not particularly limited as long as it has appropriate stretchability, flexibility, strength, and appropriate air permeability. For example, a polyester film, a polyethylene film, a polypropylene film, Plastic films such as polyvinyl chloride film, polycarbonate film, polyurethane film, polyvinyl alcohol film, ethylene vinyl acetate copolymer film and cellophane film; foam; nonwoven fabric made of polyester fiber, nylon fiber, polyethylene fiber, polypropylene fiber, etc. Examples thereof include fiber base materials such as cloth and knitted fabric; laminates thereof. From the viewpoint of stretchability, fiber substrates such as nonwoven fabrics, woven fabrics, and knitted fabrics are preferable, and knitted fabrics are more preferable. The thickness of the fiber base is usually 30 to 800 μm, preferably 100 to 700 μm, more preferably 200 to 600 μm, and the basis weight is usually 25 to 500 g / m ² , preferably 40 to 300 g / m ² , and more. Preferably it is the range of 50-200 g / m < ² >. In the case of using a fiber base as a support, a primer treatment may be applied for the purpose of improving the water-repellent treatment or the adhesiveness with the pressure-sensitive adhesive layer as desired.

(Adhesive layer)
The pressure-sensitive adhesive layer provided in the transdermal absorption patch of the present invention is a pressure-sensitive adhesive layer formed from the hot-melt type pressure-sensitive adhesive composition of the present invention described above. It is formed by coating on a support. The thickness of the pressure-sensitive adhesive layer is not particularly limited, but it is usually in the range of 50 to 400 μm, preferably 80 to 300 μm, more preferably 100 to 200 μm from the viewpoint of ensuring the fixation to the skin and the balance with the thickness of the support. It is. Also, the basis weight of the adhesive layer is generally 50 to 400 g / ^{m 2,} preferably in the range 80~300g / ^{m 2,} more preferably 100 to 200 g / ^{m 2.} The pressure-sensitive adhesive layer provided in the transdermal absorption patch of the present invention has a uniform thickness.

[Peeling sheet]
The transdermal patch of the present invention preferably further comprises a release sheet in addition to the support and the pressure-sensitive adhesive layer. The release sheet protects the pressure-sensitive adhesive layer until the transdermal absorption patch is applied to the adherend, and the hot-melt pressure-sensitive adhesive composition of the present invention is formed on the upper surface thereof as will be described in detail later. It can be used to apply an object to form an adhesive layer. As the release sheet, those commonly used in the field of patches can be used. For example, a paper base material such as high-quality paper or glassine paper subjected to silicone release treatment, a polyester film, or the like can be used. The thickness of the release sheet is usually 20 to 300 μm, preferably 30 to 200 μm, more preferably 50 to 100 μm. The basis weight of the release sheet include, but are not limited to, usually 50 to 150 g / ^{m 2,} preferably from 60 to 100 / ^{m 2.} Although one release sheet may be used, even if one release sheet is peeled off by providing one or two or more linear release sheet dividing portions that divide the outer shape at the substantially central portion of the release sheet. Alternatively, the other peeled body may remain, and a sticking operation can be performed without touching the pressure-sensitive adhesive layer to improve workability. For example, when the transdermal patch is in the form of a roll, it is particularly effective for facilitating peeling of the release sheet and improving the handleability. In addition, two or more release sheets may be arranged so that one release sheet is covered with the other release sheet or folded so that the release sheet is easily peeled off from the pressure-sensitive adhesive layer. Moreover, the width | variety of a peeling sheet is 0.2 mm or more from the viewpoint of the flow-out prevention of adhesive composition, productivity, handleability, economical efficiency, the ease of a manufacturing method, etc. from the application area | region of an adhesive, especially 1 It is preferable to increase it by -5 mm.

[Surface area of adhesive layer]
In the transdermal absorption patch of the present invention, the surface area of the pressure-sensitive adhesive layer may be the same as the surface area of the support or may be about 2 to 5% smaller. In particular, the pressure-sensitive adhesive composition of the present invention is preferably used for a small-sized transdermal absorption patch in terms of medicinal effects and adhesion. Specifically, the surface area of the pressure-sensitive adhesive layer in transdermal patches agent is preferably 4～20Cm ^2, more preferably 5 to 15 cm ^2. In the case of a circle, the diameter is preferably 2.3 to 5.0 cmφ, more preferably 2.6 to 4.3 cmφ.

[Adhesive strength of adhesive layer of transdermal patch (against BA-SUS plate adhesive strength)]
The adhesive layer of the transdermal absorption patch of the present invention exhibits an adhesive strength in the range of 0.1 to 3 N / 15 mm in a 180-degree peel test of a BA-SUS plate (Bright annealed stainless steel) according to JIS Z0237. More preferably, it is in the range of 0.5 to 2.7 N / 15 mm, more preferably 0.8 to 2.5 N / 15 mm. The transdermal patch of the present invention has a pressure-sensitive adhesive layer having an adhesive strength against BA-SUS plate within the above range, so that it does not easily peel off due to external force such as skin movement when applied to the skin. At the same time, there is no risk of feeling resistance or pain when peeling off the skin surface after applying the patch. If the adhesive strength to the BA-SUS plate is too large, there is a risk of feeling resistance or pain when peeling off the skin surface after applying the patch. The 180-degree peel test for BA-SUS plates measures the adhesive strength when a patch test piece cut to a width of 15 mm is attached to a BA-SUS plate and peeled in an 180-degree direction with an Instron type tensile tester. (Average value of n = 3).

[Retention force of adhesive layer of transdermal patches]
The pressure-sensitive adhesive layer of the transdermal absorption patch of the present invention preferably has a holding force measured in accordance with JIS Z0237 in the range of 10 to 30 minutes, more preferably in the range of 12 to 25 minutes. The transdermal absorption patch of the present invention, when the adhesive layer has a holding power in the above range, when applied to the skin, it is not easily peeled off by external force such as skin movement, and There is no fear of feeling resistance or pain when the patch is peeled from the skin. The holding force is from the time when a 200 g weight is attached to the adhesive layer of a transdermal patch having a width of 12 mm and a length of 12 mm until the test piece completely peels off the test plate. It is obtained by measuring the elapsed time (unit: minutes) (average value of n = 3).

[Probe tack of the adhesive layer of transdermal patches]
The pressure-sensitive adhesive layer of the transdermal absorption patch of the present invention preferably has a probe tack in the range of 1 to 5 N / 5 mmφ, more preferably in the range of 1.5 to 4 N / 5 mmφ. The transdermal absorption patch of the present invention has an adhesive layer having a probe tack in the above range, so that it is not easily peeled off by an external force such as the movement of the skin when applied to the skin, and There is no fear of feeling resistance or pain when the patch is peeled from the skin. The probe tack is a probe tack tester manufactured by Nichiban Co., Ltd. In accordance with the probe tack test method described in JIS Z0237 (1996 version), a cylindrical probe having a diameter of 5 mm is pulled vertically from the adhesive surface. It is obtained by measuring the force required for peeling (average value of n = 3).

[Ball tack of adhesive layer of transdermal patch]
The pressure-sensitive adhesive layer of the transdermal absorption patch of the present invention is a J.I. Ball tack according to the DOW method is No. It is preferably 20 or more, more preferably No. 25-No. A range of 32. Ball tuck Using a DOW ball tack tester, measurement was performed at an angle of 30 ° with an inclined plate at a temperature of 23 ° C. and an atmosphere of 50% RH. (The number of the largest steel ball that stops on the adhesive layer) (average value of n = 3). In addition, it shows that initial adhesiveness is so high that a ball tack is large.

10. Production method of transdermal absorption patch The production method of the transdermal absorption patch of the present invention is as long as the adhesive layer can be formed by the hot melt method using the hot melt adhesive composition of the present invention. There is no particular limitation. For example, a method of forming a pressure-sensitive adhesive layer by applying a hot-melt pressure-sensitive adhesive composition on the upper surface of a support such as a fiber substrate, and laminating a release sheet on the upper surface of the pressure-sensitive adhesive layer as desired. A method of forming a pressure-sensitive adhesive layer by melting and supplying a hot-melt pressure-sensitive adhesive composition between a support and a release sheet, or a hot-melt pressure-sensitive adhesive composition on a top surface of a release sheet by a hot-melt method There is a method in which a pressure-sensitive adhesive layer is formed by coating, and a support is laminated on the upper surface of the pressure-sensitive adhesive layer. From the viewpoint of efficiently forming an adhesive layer with a stable thickness, the melt of the hot-melt adhesive composition is supplied to the top surface of the release sheet that is continuously supplied and traveled, and coating is continuously performed. A method is preferably employed in which a pressure-sensitive adhesive layer is formed and then a support is laminated on the upper surface of the pressure-sensitive adhesive layer to obtain a transdermal absorption patch comprising the support, the pressure-sensitive adhesive layer and the release sheet. The transdermal patch having a support and an adhesive layer obtained by the above method is cut into a shape such as an ellipse, a circle, a square, a rectangle and the like according to the intended use. A skin-absorbing patch can be produced.

  The method for producing a transdermal absorption patch of the present invention is characterized in that an adhesive layer is formed by a hot melt method. The hot melt method does not use any dilution medium such as an organic solvent, and softens and melts rapidly at a high temperature. (A) Since the method uses the characteristics of a thermoplastic elastomer, a drying step is unnecessary and the coating speed is high. There are advantages such as no danger of explosion and fire. The hot melt method is not particularly limited as long as the hot melt pressure-sensitive adhesive composition can be supplied as a melt.

For example, in a rotary mixer capable of controlling the temperature, (a) a thermoplastic elastomer, (b) a tackifier resin, (c) a softener and (d) a synthetic sodium silicate are usually 100 to 200 in the air or in a nitrogen atmosphere. Each component is homogeneous by heating and stirring at a temperature of ° C, preferably 110 to 190 ° C, more preferably 120 to 180 ° C, usually 20 to 120 minutes, preferably 25 to 110 minutes, more preferably 30 to 100 minutes. The resulting melt is obtained. Next, (e) a drug is added, and further, under a nitrogen atmosphere in which air is blocked, preferably at a lower temperature than before (e) the drug is added, usually 100 to 190 ° C., preferably 105 to 180 ° C., More preferably, the mixture is heated and stirred at a temperature of 110 to 170 ° C. for 2 to 30 minutes, preferably 5 to 25 minutes, more preferably 7 to 20 minutes. A hot-melt pressure-sensitive adhesive composition is prepared. Next, the melt of the obtained hot melt pressure-sensitive adhesive composition is preferably heated on the upper surface of the release sheet, usually at a temperature of 130 to 180 ° C, preferably 135 to 175 ° C, more preferably 140 to 170 ° C. perform coating extruded at a melt coating machine, basis weight, usually 50 to 300 g / ^{m 2,} preferably 70~250g / ^{m 2,} more preferably spread so that the range of 100 to 200 g / ^{m 2} Then, the pressure-sensitive adhesive layer having the desired thickness is formed. As the hot melt coater, a commonly used coater can be used. Specifically, an extruder equipped with a T-type die head or the like can be used. Further, in order to spread the hot melt pressure-sensitive adhesive composition, pressure may be applied by a temperature-controlled roll. As the temperature-controlled roll, two or more rolls adjusted to different temperatures may be used, and pressure may be applied between the rolls.

  The hot melt pressure-sensitive adhesive composition of the present invention has a low melt viscosity at the time of melting, and preferably has a melt viscosity at a temperature of 150 ° C. of 250 dPa · s or less. Since it can be set and applied, in the process from the production of the hot melt adhesive composition to the production of the transdermal absorption patch, (e) the drug flows out or volatilizes. In addition, (e) it is possible to prevent the drug from being decomposed or deteriorated by heat and to increase the coating speed, which is preferable in terms of production efficiency.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples and comparative examples, but the present invention is not limited to these examples. The method for measuring the characteristics or physical properties of the hot melt pressure-sensitive adhesive composition or transdermal absorption patch of the present invention is as follows.

[Melt viscosity]
The melt viscosity of the hot-melt pressure-sensitive adhesive composition was measured using a B-type viscometer (measurement conditions were a temperature of 150 ° C., rotor No. 3, 62.5 rpm, 30 seconds).

[Adhesive strength of adhesive layer of transdermal patch (against BA-SUS plate adhesive strength)]
The adhesive strength of the adhesive layer of the transdermal patch was measured by a 180 ° peel test of a BA-SUS plate (Bright annealed stainless steel) according to JIS Z0237. Specifically, a test piece of a patch cut out to a width of 15 mm was attached to a BA-SUS plate, and the adhesive strength was measured when it was peeled off in the direction of 180 degrees with an Instron type tensile tester (average of n = 3). value).

[Retention force of adhesive layer of transdermal patches]
The holding power of the adhesive layer of the transdermal absorption patch is based on JIS Z0237, after attaching a 200 g weight to the adhesive layer of the transdermal absorption patch having a width of 12 mm and a length of 12 mm, The elapsed time (unit: minute) until the test piece completely peeled off from the test plate was measured (average value of n = 3).

[Probe tack of the adhesive layer of transdermal patches]
The probe tack of the adhesive layer of the transdermal patch is a cylindrical probe having a diameter of 5 mm using a probe tack tester manufactured by Nichiban Co., Ltd. according to the probe tack test method described in JIS Z0237 (1996 version) as a reference. It was determined by measuring the force required to peel the film from the adhesive surface in the vertical direction (average value of n = 3).

[Ball tack of adhesive layer of transdermal patch]
The ball tack of the pressure-sensitive adhesive layer of the transdermal absorption patch is determined according to J.I. Using a DOW ball tack tester, the angle of the inclined plate was measured at a temperature of 23 ° C. and a 50% RH atmosphere at an angle of 30 °. (Average value of n = 3).

[Example 1]
[Preparation of hot-melt adhesive composition]
Hot melt pressure-sensitive adhesive compositions containing (a) to (f) having the compositions shown in Table 1 below were prepared by the following method. That is, among the components (a) to (f) in the proportions shown in <Adhesive composition> below, the components (a) to (d) and (f) are blended and the temperature is 150 ° C. for 40 minutes. A melt in which each component became uniform was obtained by heating and stirring. Next, the stirring is stopped once (e) the drug is added, sealed to prevent volatilization of the drug, and the stirring is continued for 10 minutes at a temperature of 150 ° C. in a nitrogen atmosphere with the air shut off to melt the drug. A hot-melt pressure-sensitive adhesive composition in a state was prepared. The melt viscosity at a temperature of 150 ° C. of the hot melt pressure-sensitive adhesive composition (hereinafter sometimes simply referred to as “melt viscosity”) was 150 dPa · s. In addition, the drug (e) compounded in the hot melt pressure-sensitive adhesive composition has an 11% increase in each content shown in Table 1 in consideration of loss due to volatilization (addition amount determined in advance). The amount of parts by mass corresponding to the above is blended.

<Adhesive composition>
(A) Thermoplastic elastomer [(a1) SIS block copolymer (1), SIS5002 manufactured by JSR Corporation] 25.3 parts by mass (a) Thermoplastic elastomer [(a2) SIS block copolymer (2), Quintac (registered trademark) 3520 manufactured by Nippon Zeon Co., Ltd.] 10.9 parts by mass (b) Tackifying resin [(b1) Rosin resin, KE-311 manufactured by Arakawa Chemical Industries, Ltd.] 21.7 parts by mass ( b) Tackifying resin [(b2) Terpene resin manufactured by Yasuhara Chemical Co., Ltd., YS Resin PX1150N] 14.5 parts by mass (c) Softening agent [Paraffinic oil manufactured by Kaneda Co., Ltd. ) M-352] 6.0 parts by mass (d) Light synthetic aluminum silicate (Kyowa Chemical Industry Co., Ltd.) 3.0 parts by mass (e) Drug 20.6 2 parts by mass (total content)
<Breakdown of drugs>
Methyl salicylate 8.3 parts by mass l-menthol 8.3 parts by mass dl-camphor 4.0 parts by mass Nonyl acid vanillylamide 0.02 parts by mass (Note that the drug is a hot-melt adhesive composition according to this example. Since it has been confirmed that the amount equivalent to 11%, which is the added amount, is lost at the time of coating and coating, the content of the drug (e) in the pressure-sensitive adhesive layer formed from the hot-melt pressure-sensitive adhesive composition is The total amount is 18.58 parts by mass, and the mass% is shown in Table 1.)
(F) Anti-aging agent [BHT (di-tert-butylhydroxytoluene)] 0.35 parts by mass

[Manufacture of transdermal patches]
The obtained hot melt pressure-sensitive adhesive composition was supplied to a hot melt coating machine, melted at a temperature of 150 ° C., and a 75 μm thick polyester film (release sheet) treated with silicone was run on the upper surface of the film. , Hot melt type adhesion to a release sheet by melt extrusion from a T-type die head with a width of 200 mm at a feed rate of 150 g / m ² followed by clamping with a roll at a temperature of 130 ° C. and a back roll at a temperature of 60 ° C. The adhesive composition was applied to form an adhesive layer having a thickness of 150 μm. Next, a polyester knitted fabric (thickness 400 μm, basis weight 125 g / m ² ) serving as a support is laminated on the upper surface of the pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer formed from the support, the hot-melt pressure-sensitive adhesive composition, and An original fabric of a transdermal absorption patch provided with a release sheet was obtained. Subsequently, a percutaneous absorption patch comprising a support, a pressure-sensitive adhesive layer formed from a hot-melt pressure-sensitive adhesive composition, and a release sheet was produced by punching into a frame shape so as to form a circle of 28 mmφ (2.8 cmφ). . For the original fabric of the transdermal absorption patch, the adhesive strength of the adhesive layer measured by the method described above was 1.72 N / 15 mm. The holding force was 18.3 minutes, the probe tack was 2.37 N / 5 mmφ, and the ball tack was No. 31. The thickness of the pressure-sensitive adhesive layer was uniform by visual observation. The results are shown in Table 1.

[Example 2]
(D) A hot melt pressure-sensitive adhesive composition was prepared in the same manner as in Example 1 except that the synthetic aluminum silicate was changed to heavy synthetic aluminum silicate (manufactured by Kyowa Chemical Industry Co., Ltd.). The melt viscosity of the hot melt pressure-sensitive adhesive composition was 150 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. The thickness of the pressure-sensitive adhesive layer was uniform by visual observation. The results are shown in Table 1.

[Example 3]
(D) A hot-melt pressure-sensitive adhesive composition was prepared in the same manner as in Example 1 except that the synthetic aluminum silicate was changed to extra light synthetic aluminum silicate (manufactured by Kyowa Chemical Industry Co., Ltd.). The melt viscosity of the hot melt pressure-sensitive adhesive composition was 150 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. The thickness of the pressure-sensitive adhesive layer was uniform by visual observation. The results are shown in Table 1.

[Example 4]
(D) Except that the content of synthetic aluminum silicate was 5.0% by mass and the contents of (a) to (c), (e) and (f) were changed as shown in Table 1. In the same manner as in Example 1, a hot-melt pressure-sensitive adhesive composition was prepared. The melt viscosity of the hot melt pressure-sensitive adhesive composition was 150 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. The thickness of the pressure-sensitive adhesive layer was uniform by visual observation. The results are shown in Table 1.

[Example 5]
(D) Except that the content of synthetic aluminum silicate was 7.0% by mass and the contents of (a) to (c), (e) and (f) were changed as shown in Table 1. In the same manner as in Example 1, a hot-melt pressure-sensitive adhesive composition was prepared. The melt viscosity of the hot melt pressure-sensitive adhesive composition was 150 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. The thickness of the pressure-sensitive adhesive layer was uniform by visual observation. The results are shown in Table 1.

[Comparative Example 1]
(D) A hot melt pressure-sensitive adhesive composition was prepared in the same manner as in Example 1 except that zinc oxide (manufactured by Miike Smelting Co., Ltd.) was used instead of synthetic aluminum silicate. The melt viscosity of the hot melt pressure-sensitive adhesive composition was 300 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. A slight thickness unevenness was observed in the pressure-sensitive adhesive layer by visual observation. The results are shown in Table 1.

[Comparative Example 2]
(D) In the same manner as in Example 1, except that calcium carbonate [trade name: Whiten (registered trademark) P-40 manufactured by Shiroishi Kogyo Co., Ltd.] was used instead of synthetic aluminum silicate, A mold pressure-sensitive adhesive composition was prepared. The melt viscosity of the hot melt pressure-sensitive adhesive composition was 300 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. A slight thickness unevenness was observed in the pressure-sensitive adhesive layer by visual observation. The results are shown in Table 1.

[Comparative Example 3]
(D) A hot melt pressure-sensitive adhesive composition was prepared in the same manner as in Example 1 except that titanium oxide (titanium oxide A-150 manufactured by Sakai Chemical Industry Co., Ltd.) was used instead of synthetic aluminum silicate. Prepared. The melt viscosity of the hot melt pressure-sensitive adhesive composition was 300 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. A slight thickness unevenness was observed in the pressure-sensitive adhesive layer by visual observation. The results are shown in Table 1.

[Comparative Example 4]
(D) As in Example 1, except that no synthetic aluminum silicate was added and the contents of (a) to (c), (e) and (f) were changed as shown in Table 1. Thus, a hot melt pressure-sensitive adhesive composition was prepared. The melt viscosity of the hot melt pressure-sensitive adhesive composition was 450 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. A slight thickness unevenness was observed in the pressure-sensitive adhesive layer by visual observation. The results are shown in Table 1.

[Comparative Example 5]
(D) Except that the content of synthetic aluminum silicate was 1.0% by mass and the contents of (a) to (c), (e) and (f) were changed as shown in Table 1. In the same manner as in Example 1, a hot-melt pressure-sensitive adhesive composition was prepared. The melt viscosity of the hot melt pressure-sensitive adhesive composition was 300 dPa · s. The obtained hot melt pressure-sensitive adhesive composition was melted at a temperature of 150 ° C. in the same manner as in Example 1 and applied to the upper surface of the release sheet to form a pressure-sensitive adhesive layer. Next, after laminating a polyester knitted fabric as a support on the upper surface of the pressure-sensitive adhesive layer, it is punched into a frame shape so as to form a 28 mmφ circle, and the pressure-sensitive adhesive formed from the support and the hot-melt pressure-sensitive adhesive composition A transdermal absorption patch comprising an agent layer and a release sheet was produced. A slight thickness unevenness was observed in the pressure-sensitive adhesive layer by visual observation. The results are shown in Table 1.

[Comparative Example 6]
(D) Except that the content of synthetic aluminum silicate is 10.0% by mass and the contents of (a) to (c), (e) and (f) are changed as shown in Table 1. In the same manner as in Example 1, a hot-melt pressure-sensitive adhesive composition was prepared. After 10 minutes from the start of heating and stirring, the viscosity increased and the pressure-sensitive adhesive composition containing excessive air rose up to the top surface of the stirring container, so that further stirring was not continued. Measurement of melt viscosity and coating were not possible.

From Table 1, the following components (a) to (e):
(A) Thermoplastic elastomer 25-50 mass%,
(B) Tackifying resin 20-50% by mass,
(C) Softener 5-9% by mass,
(D) Synthetic aluminum silicate 2-8% by mass and (e) Drug 10-25% by mass
[However, the sum of (a) to (e) is 100% by mass. ]
The hot-melt pressure-sensitive adhesive compositions of Examples 1 to 5 that contain the melt viscosity of 250 dPa · s or less at a temperature of 150 ° C. are excellent in coating properties, and the thickness of the pressure-sensitive adhesive layer formed from the composition Was found to be uniform. In particular, for the transdermal absorption patch comprising the support of Example 1 and the adhesive layer formed from the hot melt adhesive composition, the adhesive strength of the adhesive layer is 1.72 N / 15 mm, the holding power. Is 18.3 minutes, the probe tack is 2.37 N / 5 mmφ, and the ball tack value is No. Therefore, when it is applied to the skin, it does not easily peel off due to external force such as the movement of the skin, and the patch is peeled off from the skin. It was found that there was no fear of feeling resistance or pain.

  On the other hand, instead of (d) synthetic aluminum silicate, the hot melt type of Comparative Examples 1 to 3 containing zinc oxide, calcium carbonate, or titanium oxide, which has been conventionally used as a filler contained in an adhesive. It was found that the pressure-sensitive adhesive composition had a melt viscosity of 300 dPa · s at a temperature of 150 ° C. and insufficient coatability, and a slight thickness unevenness was observed in the pressure-sensitive adhesive layer.

  Further, (d) the hot melt pressure-sensitive adhesive composition of Comparative Example 4 that does not contain synthetic aluminum silicate, and (d) 1.0 mass out of the range of 2 to 8 mass% of the synthetic aluminum silicate content. %, The hot melt pressure-sensitive adhesive composition of Comparative Example 5 has a melt viscosity of 300 to 450 dPa · s at a temperature of 150 ° C. and has insufficient coatability, and the pressure-sensitive adhesive layer exhibits a slight thickness unevenness. I found out that Furthermore, (d) the hot melt pressure-sensitive adhesive composition of Comparative Example 6 in which the content of the synthetic aluminum silicate is 10.0% by mass outside the range of 2 to 8% by mass includes the pressure-sensitive adhesive layer in the patch. I found it difficult to form.

The present invention includes the following components (a) to (e):
(A) Thermoplastic elastomer 25-50 mass%,
(B) Tackifying resin 20-50% by mass,
(C) Softener 5-9% by mass,
(D) Synthetic aluminum silicate 2-8% by mass and (e) Drug 10-25% by mass
[However, the sum of (a) to (e) is 100% by mass. ]
A hot melt pressure-sensitive adhesive composition containing a drug having a drug content of 10% by mass or more. A hot-melt pressure-sensitive adhesive composition that can retain cohesive force and is excellent in coating suitability is provided, and a transdermal device comprising a support and a pressure-sensitive adhesive layer formed from the hot-melt pressure-sensitive adhesive composition Since an absorbent patch can be provided, the industrial applicability is high.

Claims (9)

The following components (a) to (e):
(A) Thermoplastic elastomer 25-50 mass%,
(B) Tackifying resin 20-50% by mass,
(C) Softener 5-9% by mass,
(D) Synthetic aluminum silicate 2-8% by mass and (e) Drug 10-25% by mass
[However, the sum of (a) to (e) is 100% by mass. ]
A hot-melt pressure-sensitive adhesive composition comprising:   The hot melt pressure-sensitive adhesive composition according to claim 1, wherein (a) the thermoplastic elastomer contains a styrenic thermoplastic elastomer, and (e) the drug contains a drug that is liquid at room temperature. .   The hot-melt pressure-sensitive adhesive composition according to claim 1 or 2, wherein the (b) tackifying resin contains a rosin resin and the (c) softening agent is a naphthenic or paraffinic oil. .   The hot melt pressure-sensitive adhesive composition according to any one of claims 1 to 3, wherein the (d) synthetic aluminum silicate is light synthetic aluminum silicate.   The hot melt pressure-sensitive adhesive composition according to any one of claims 1 to 4, obtained from a composition having a melt viscosity of 250 dPa · s or less at a temperature of 150 ° C.   A transdermal patch comprising a support and a pressure-sensitive adhesive layer formed from the hot-melt pressure-sensitive adhesive composition according to any one of claims 1 to 5.   The transdermal patch according to claim 6, wherein the support is a fiber substrate.   The transdermal absorption patch according to claim 6 or 7, further comprising a release sheet. The transdermal patch according to any one of claims 6 to 8, wherein the adhesive layer has a surface area of 4 to ²⁰ cm2.