WO2002040031A1 - Adhesive preparation containing estradiol - Google Patents

Adhesive preparation containing estradiol Download PDF

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Publication number
WO2002040031A1
WO2002040031A1 PCT/JP2001/009915 JP0109915W WO0240031A1 WO 2002040031 A1 WO2002040031 A1 WO 2002040031A1 JP 0109915 W JP0109915 W JP 0109915W WO 0240031 A1 WO0240031 A1 WO 0240031A1
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WO
WIPO (PCT)
Prior art keywords
patch
estradiol
drug
sensitive adhesive
liquid
Prior art date
Application number
PCT/JP2001/009915
Other languages
French (fr)
Japanese (ja)
Inventor
Susumu Maruo
Hiroyuki Waseda
Nobuaki Hanajima
Original Assignee
Teijin Limited
Teysan Pharmaceuticals Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Teijin Limited, Teysan Pharmaceuticals Co., Ltd. filed Critical Teijin Limited
Priority to KR10-2003-7006318A priority Critical patent/KR100533493B1/en
Priority to JP2002542404A priority patent/JP3935839B2/en
Priority to AU2002212763A priority patent/AU2002212763A1/en
Publication of WO2002040031A1 publication Critical patent/WO2002040031A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30—Oestrogens

Definitions

  • the present invention relates to a patch containing extradiol. Background art
  • the estrogen, estradiol is also disclosed in, for example, Japanese Patent Application Publication No. 3-520925 and Japanese Patent Application Publication No. 6-5303756, in which Absorption enhancers have been proposed to improve the absorption.
  • Absorption enhancers have been proposed to improve the absorption.
  • An object of the present invention is to provide a patch which is excellent in skin permeability of estradiol, maintains the skin permeability for a long time, and is excellent in safety and economy.
  • the present inventors have conducted intensive studies to achieve such an object, and have found that a specific absorption promoter is used in a patch provided with an adhesive layer containing estradiol, an absorption accelerator, and an adhesive. As a result, it has been found that the object of the present invention is achieved, and the present invention has been completed. Disclosure of the invention
  • the present invention provides a patch in which an adhesive layer containing a drug, an absorption promoter and an adhesive is provided on one surface of a flexible support,
  • the drug is estradiol
  • the absorption enhancer comprises at least one selected from sorbitan monolaurate and polyethylene glycol monolaurate, and at least one selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature;
  • the pressure-sensitive adhesive is an acrylic pressure-sensitive adhesive
  • the absorption promoter used in the present invention is selected from sorbitan monolaurate and polyethylene glycol monolaurate-and one selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature. It is important that this is a mixture of the above. Only when this mixture is used, it is possible to obtain a patch having excellent transdermal absorbability and long-lasting skin permeability of estradiol.
  • the absorption promoter is at least one selected from sorbitan monolaurate and polyethylene glycol monolaurate, a patch having the above properties cannot be obtained. Similarly, even when only one or more selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature, such patches cannot be obtained.
  • At least one selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature is preferably a mixture of higher fatty acid esters and hydrocarbons. This is because it is effective not only in improving and sustaining the absorption of estradiol, but also in terms of skin adhesion and economics.
  • the mixing ratio is preferably 0.1: 0.9 force, and 0.8: 0.2.
  • the absorption enhancer of the present invention is preferably sorbitan monolaurate from the viewpoints of improving the absorption of estradiol, continuously improving the absorption, adhesion to the skin, economy, and water resistance to bathing. It is particularly preferred that the mixture is a mixture of carboxylic acids, higher fatty acid esters, and hydrocarbons.
  • Examples include isopropyl succinate, isopropyl palmitate, isostearyl palmitate, ethyl oleate, oleyl oleate, decyl oleate, getyl sebacate, and hexyl laurate.
  • isopropyl myristate, isopropyl palmitate, or ethyl oleate are preferred from the viewpoints of improving the absorption of estradiol, maintaining the effect over a long period of time, and irritating the skin.
  • isopropyl myristate can be mentioned as a particularly preferred one.
  • hydrocarbons according to the present invention examples include liquid paraffin, squalane, squalene, gelled hydrocarbons, and petrolatum. Liquid paraffin and / or squalane are preferred from the viewpoints of improvement, sustained absorption, economy and adhesive strength.
  • the content of one or more selected from sorbitan monolaurate and polyethylene glycol monolaurate in the pressure-sensitive adhesive layer is preferably 2 wt% or more and 10 wt% or less.
  • the content is less than 2 wt%, it is difficult to improve the sufficient skin permeability of the drug, and when the content exceeds 1 wt%, the effect of improving the skin permeability of the drug is leveled off. Therefore, it is not preferable in terms of safety and economy.
  • the content in one or more pressure-sensitive adhesive layers selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature is preferably 5 wt% or more and 35 wt% or less. If the content is less than 5 wt%, it is difficult to maintain sufficient skin permeability of the drug and long-term skin permeability. On the other hand, if it exceeds 35 wt%, the effect of improving the skin permeability of the drug is improved. As the fruits peak, they are less favorable from an economic point of view. In addition, when the patch is applied to the skin and peeled off, glue residue easily forms on the skin.
  • the acryl-based pressure-sensitive adhesive in the present invention contains an alkyl (meth) acrylate having 2 to 20 carbon atoms as a main component, and has an (meth) acrylate of 10% or less. ) Acrylic acid-containing (meth) alkyl acrylate copolymers are preferred.
  • the alkyl (meth) acrylate having 2 to 20 carbon atoms include ethyl (meth) acrylate, butyl (meth) acrylate, and pentyl (meta).
  • (meth) alkyl acrylate means an alkyl acrylate or an alkyl methacrylate.
  • an acrylic adhesive may be mixed with a vinyl acetate adhesive or a silicone adhesive in an amount less than the equivalent amount of the acrylic adhesive.
  • estradiol of the present invention refers to natural estrogen, synthetic estrogen, and derivatives thereof, for example, estradiol benzoate, estradiol benzoate, estradiol dipropionate, Estradiol valerate, ethynyl estradiol, and the like. Among them, estradiol is preferred.
  • the content of the estradionil of the present invention in the patch is preferably 0.4 wt% or more and 2.5 wt% or less, particularly preferably 0.6 wt% or more and 2.01% or less. . If the content is less than 0.4 wt%, it is difficult to obtain a sufficient amount of the drug through the skin. On the other hand, if the content exceeds 2.5 wt%, it is uneconomical because the amount of residual drug in the patch after use increases.
  • a conventionally known method can be employed as a method for incorporating a drug into the pressure-sensitive adhesive layer.
  • a method for incorporating a drug into the pressure-sensitive adhesive layer a conventionally known method can be employed.
  • a method in which a drug solution is preliminarily mixed with a solution-type pressure-sensitive adhesive to form a drug-containing pressure-sensitive adhesive layer, or a pressure-sensitive adhesive layer that does not contain a drug or does not sufficiently contain a drug is impregnated, inverted, or This is a method in which the drug is contained in a sufficient amount for transdermal absorption by wearing or spraying.
  • Crosslinking may be performed in the pressure-sensitive adhesive layer of the present invention for the purpose of improving the cohesive strength of the pressure-sensitive adhesive layer.
  • a cross-linking method include cross-linking by ultraviolet rays or ultraviolet rays, or the use of a polymer such as a caustic anhydride, a polyisocyanate compound, an organic metal salt, a metal chelate compound, or a polymer capable of forming a polyion complex.
  • a method of adding a crosslinking agent to perform crosslinking can be used.
  • stabilizers such as magnesium stearate, zinc stearate, and citric anhydride; for example, ascorbic acid, toco acetate Antioxidants such as ferol and vitamin E; fragrances such as menthol, potato fulness, oil, lemon oil; preservatives such as dibutylhydroxytoluene and isobutyl paraoxybenzoate;
  • pH adjusters such as sodium citrate, sodium dihydrogen citrate, sodium hydrogen phosphite, sodium hydrogen phosphite and the like can be mentioned. These can be used alone or in combination of one or more.
  • the support used in the present invention is not particularly limited as long as it can adhere an adhesive layer and has a self-shape retention property.
  • the material and shape are not particularly limited. Absent.
  • polymer films such as polyester, polyolefin, polyvinyl chloride, polyurethane, and cellulose ester; fibers such as polyester, polyolefin, polyurethane, cellulose ester, and polyamide.
  • the thickness of the support is not particularly limited, but is preferably 50 to 100 m from the viewpoint of handleability.
  • the thickness of the pressure-sensitive adhesive layer in the present invention is not particularly limited, but is preferably from 10 to 300 m, and particularly preferably from 40 to 200 m.
  • sorbitan monolaurate and polyethylene are used as absorption accelerators.
  • Polyacrylic acid alkyl ester copolymer solution consisting of 90% 2-ethylhexyl acrylate, 7% methyl methacrylate, and 3% acrylic acid as an acrylic adhesive (Solid content: 15%) 24.3 parts: 1.2 parts of a 5% solution of estradiol in acetate, 0.2 part: sorbitan monolaurate: 0.25 parts, isopropyl myristate: 1.0 Parts, 0.05 parts of polyvinylpyrrolidone, 19 parts of ethyl acetate and 13 parts of ethanol were added as a crosslinking agent.
  • a patch was obtained in the same manner as in Example 1 except that the composition shown in Table 1 was changed.
  • Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Comparative Example 1 Comparative Example 2 Estradiol 1.2 1.2 0.8 1.2 1.2 1.8 1.2 1.2 1.2 1.2 Acrylic adhesive 72.8 85.3 74.1 73.7 73.7 82.7 72.8 78.3 72.8 92.8 Sorbitan monolaurate 5 2.5 5 5 5 5 5 5 Poly-polykishetylene monolaurate 5 5
  • Crosslinker 1 1 0.1 0.1 0.1 0.5 1 0.5 1 1 1 Blood drug concentration: 7 hours after application 4168 3802 3959 4103 3756 6432 3929 4005 2183 1343 (pg / ml): 24 hours after application 1938 1462 2505 2342 1625 2362 1618 2156 960 812

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Abstract

An adhesive preparation which comprises a flexible support and formed on one side thereof a pressure-sensitive adhesive layer comprising a drug, an absorption accelerator, and a pressure-sensitive adhesive, wherein (i) the drug is estradiol, (ii) the absorption accelerator comprises a combination of at least either of sorbitan monolaurate and polyethylene glycol monolaurate and at least one member selected among higher fatty acid esters which are liquid at room temperature and hydrocarbons which are liquid at room temperature, and (iii) the pressure-sensitive adhesive is an acrylic one.

Description

明 細 書 エス トラジオール含有貼付剤 技術分野  Description Technical patch containing estradiol
本発明はエス 卜ラジオールを含有する貼付剤に関する。 背景技術  The present invention relates to a patch containing extradiol. Background art
閉経後の女性に観察される更年期障害、 骨粗しょ う症、 アルッハ イマ一痴呆症等の原因として、 閉経に伴う卵胞ホルモンの減少が指 摘されている。 現在、 上記の症状に対して経口剤等による補充療法 が行われている。  Menstrual disorders, osteoporosis, and Alheima dementia, which are observed in postmenopausal women, have been pointed out by decreased menstrual estrogen. At present, replacement therapy with oral preparations is being performed for the above symptoms.
しかしながら、 経口剤の場合、 消化管及び肝臓ですみやかに代謝 されてしまうため、 多量の投与が必要となる。 近年、 肝臓での代謝 (初回通過効果） を回避する方法として、 薬物を皮膚面を通して体 内に投与する経皮吸収テープが開発されている。  However, in the case of oral preparations, it is rapidly metabolized in the gastrointestinal tract and liver, so large doses are required. In recent years, as a method of avoiding metabolism (first-pass effect) in the liver, transdermal absorption tapes that administer drugs into the body through the skin surface have been developed.
一般に、 皮膚からの薬物の透過は低いために、 薬物の皮膚からの 吸収性を向上させる方法が提案されている （例えば、 特開平 1 — 2 3 3 2 1 3号公報、 特開平 5 — 1 7 8 7 6 3号公報、 及び特開平 6 一 2 0 5 8 3 9号公報） 。  In general, because the permeation of a drug from the skin is low, a method for improving the absorbability of the drug from the skin has been proposed (for example, Japanese Patent Application Laid-Open Nos. 1-233, 55-1). Japanese Patent Application Laid-Open No. 787663 and Japanese Patent Application Laid-Open No. Hei 6-205 839).
また、 卵胞ホルモンであるエス ト ラジオールに関しても、 例えば 特表平 3 — 5 0 2 9 2 5号公報、 及び特表平 6 — 5 0 3 5 7 6号公 報でエス ト ラジオールの皮膚吸収性を向上させるための吸収促進剤 が提案されている。 しかしながら これらの技術においては、 薬物の皮膚透過性を向上 させることは可能だが、 効果が不十分である、 皮膚透過性向上が持 続しない、 また、 安全性や経済性の点でいまだ満足できるものが得 られていない。 The estrogen, estradiol, is also disclosed in, for example, Japanese Patent Application Publication No. 3-520925 and Japanese Patent Application Publication No. 6-5303756, in which Absorption enhancers have been proposed to improve the absorption. However, with these technologies, it is possible to improve the skin permeability of drugs, but the effect is insufficient, skin permeability improvement is not sustained, and safety and economy are still satisfactory. Has not been obtained.
本発明の目的は、 エス ト ラジオールの皮膚透過性に優れ、 かつ長 時間にわたって皮膚透過性の向上が持続し、 また安全性や経済性に 優れた貼付剤を提供する こ とである。  An object of the present invention is to provide a patch which is excellent in skin permeability of estradiol, maintains the skin permeability for a long time, and is excellent in safety and economy.
本発明者らは、 かかる目的を達成するために鋭意研究した結果、 エス トラジオールと吸収促進剤及び粘着剤を含有する粘着剤層が設 けられた貼付剤において、 特定の吸収促進剤を用いる ことによ り、 上記本発明の目的が達成される ことを見出し本発明を完成した。 発明の開示  The present inventors have conducted intensive studies to achieve such an object, and have found that a specific absorption promoter is used in a patch provided with an adhesive layer containing estradiol, an absorption accelerator, and an adhesive. As a result, it has been found that the object of the present invention is achieved, and the present invention has been completed. Disclosure of the invention
すなわち本発明は、 柔軟な支持体の片面に薬物と吸収促進剤及び 粘着剤を含有する粘着剤層が設けられた貼付剤において、  That is, the present invention provides a patch in which an adhesive layer containing a drug, an absorption promoter and an adhesive is provided on one surface of a flexible support,
( 1 ) 該薬物が、 エス ト ラジオールであり、  (1) the drug is estradiol,
( i i ) 該吸収促進剤が、 ソルビタンモノ ラウレー ト及びポリェ チレングリ コールモノ ラウ レー 卜から選ばれる一以上と、 室温で液 状の高級脂肪酸エステル及び炭化水素類から選ばれる一種以上とか らなり、  (ii) the absorption enhancer comprises at least one selected from sorbitan monolaurate and polyethylene glycol monolaurate, and at least one selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature;
( i i i ) 該粘着剤が、 アク リル系粘着剤である  (iii) the pressure-sensitive adhesive is an acrylic pressure-sensitive adhesive
貼付剤を提供するものである。 発明を実施するための最良の形態 本発明において用いられる吸収促進剤は、 ソルビタンモノ ラウ レ 一卜及びポリ エチレングリ コールモノ ラウ レー トか ら選ばれるー以 上と、 室温で液状の高級脂肪酸エステル及び炭化水素類から選ばれ る一種以上との混合物である こ とが重要である。 こ の混合物を用い た場合のみ、 優れた経皮吸収性及びエス ト ラジオールの皮膚透過性 が長時間持続する貼付剤を得る ことができる。 It is intended to provide a patch. BEST MODE FOR CARRYING OUT THE INVENTION The absorption promoter used in the present invention is selected from sorbitan monolaurate and polyethylene glycol monolaurate-and one selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature. It is important that this is a mixture of the above. Only when this mixture is used, it is possible to obtain a patch having excellent transdermal absorbability and long-lasting skin permeability of estradiol.
該吸収促進剤が、 ソルビ夕 ンモノ ラウレー ト及びポリ エチレング リ コールモノ ラウ レー 卜から選ばれる一以上だけの場合は上記特性 を有する貼付剤は得られない。 同様に、 室温で液状の高級脂肪酸ェ ステル及び炭化水素類から選ばれる一種以上だけの場合でも、 かか る貼付剤は得られない。  When the absorption promoter is at least one selected from sorbitan monolaurate and polyethylene glycol monolaurate, a patch having the above properties cannot be obtained. Similarly, even when only one or more selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature, such patches cannot be obtained.
本発明において、 室温で液状の高級脂肪酸エステル及び炭化水素 類よ り選ばれる一種以上は、 高級脂肪酸エステルと炭化水素類の混 合物である ことが好ましい。 なぜなら、 エス ト ラジオールの吸収性 向上や持続性の点だけでなく 、 皮膚に対する粘着力、 経済性の点で 効果的だからである。  In the present invention, at least one selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature is preferably a mixture of higher fatty acid esters and hydrocarbons. This is because it is effective not only in improving and sustaining the absorption of estradiol, but also in terms of skin adhesion and economics.
上記高級脂肪酸エステルと炭化水素類との混合物を用いる場合、 その混合比は、 0 . 1 : 0 . 9 力、ら 0 . 8 : 0 . 2 が好ましい。 更に、 本発明における吸収促進剤は、 エス ト ラジオールの吸収性 向上、 持続的な吸収性の向上、 皮膚に対する粘着力、 経済性、 また は入浴等に対する耐水性の点か ら、 ソルビタンモノ ラウ レー ト、 高 級脂肪酸エステル、 及び炭化水素類の混合物である こ とが特に好ま しい。  When a mixture of the above-mentioned higher fatty acid ester and hydrocarbons is used, the mixing ratio is preferably 0.1: 0.9 force, and 0.8: 0.2. Furthermore, the absorption enhancer of the present invention is preferably sorbitan monolaurate from the viewpoints of improving the absorption of estradiol, continuously improving the absorption, adhesion to the skin, economy, and water resistance to bathing. It is particularly preferred that the mixture is a mixture of carboxylic acids, higher fatty acid esters, and hydrocarbons.
本発明における室温で液状の高級脂肪酸エステルと しては、 ミ リ スチン酸イ ソプロ ピル、 パルミチン酸イ ソプロ ピル、 パルミチン酸 イ ソステア リ ル、 ォレイ ン酸ェチル、 ォレイ ン酸ォレイル、 ォレイ ン酸デシル、 セバシン酸ジェチル、 及びラウ リ ン酸へキシルなどが あげられる。 これらの中でも、 エス ト ラジオールの吸収性の向上、 長時間にわたる効果の持続性や皮膚刺激性の点から ミ リ スチン酸ィ ソプロ ピル、 パルミチン酸イ ソプロ ピル、 またはォレイ ン酸ェチル が好ま しい。 さ ら に、 ミ リスチン酸イ ソプロ ピルを特に好ま しいも のとして挙げることができる。 As the higher fatty acid ester liquid at room temperature in the present invention, Examples include isopropyl succinate, isopropyl palmitate, isostearyl palmitate, ethyl oleate, oleyl oleate, decyl oleate, getyl sebacate, and hexyl laurate. Among these, isopropyl myristate, isopropyl palmitate, or ethyl oleate are preferred from the viewpoints of improving the absorption of estradiol, maintaining the effect over a long period of time, and irritating the skin. In addition, isopropyl myristate can be mentioned as a particularly preferred one.
本発明におはる炭化水素類と しては、 流動パラフィ ン、 スク ワ ラ ン、 スク ワ レン、 ゲル化炭化水素、 及びワセリ ンなどがあげられる これらの中でも、 エス ト ラジオールの吸収性の向上、 持続的な吸収 性の向上、 経済性及び粘着力の点から流動パラフィ ン及び/ ^又はス クヮランが好ましい。  Examples of the hydrocarbons according to the present invention include liquid paraffin, squalane, squalene, gelled hydrocarbons, and petrolatum. Liquid paraffin and / or squalane are preferred from the viewpoints of improvement, sustained absorption, economy and adhesive strength.
本発明において、 粘着剤層中のソルビタ ンモノ ラウレ一 卜及びポ リ エチレングリ コールモノ ラウレー トから選ばれる一以上の含有量 は、 2 w t %以上 1 0 w t %以下である こ とが好ま しい。 含有量が 2 w t %未満では、 薬物の十分な皮膚透過性を向上させる こ とが困 難とな り、 また 1 O w t %を超える と薬物の皮膚透過性の向上の効 果が頭打ちになるので、 安全性や経済性の点から好ましく ない。  In the present invention, the content of one or more selected from sorbitan monolaurate and polyethylene glycol monolaurate in the pressure-sensitive adhesive layer is preferably 2 wt% or more and 10 wt% or less. When the content is less than 2 wt%, it is difficult to improve the sufficient skin permeability of the drug, and when the content exceeds 1 wt%, the effect of improving the skin permeability of the drug is leveled off. Therefore, it is not preferable in terms of safety and economy.
また、 室温で液状の高級脂肪酸エステル及び炭化水素類よ り選ば れる一種以上の粘着剤層中での含有量は 5 w t %以上 3 5 w t %以 下である こ とが好ま しい。 含有量が 5 w t %未満では、 十分な薬物 の皮膚透過性及び長時間にわたる皮膚透過性を持続性する こ とが難 しい。 また、 3 5 w t %を超える と、 薬物の皮膚透過性の向上の効 果が頭打ち になるため、 経済性の点か ら好ま し く な く なる。 加えて 貼付剤を皮膚に適用 した後それを剥がす際に皮膚に糊残 り が生 じや すく なる。 Further, the content in one or more pressure-sensitive adhesive layers selected from higher fatty acid esters and hydrocarbons which are liquid at room temperature is preferably 5 wt% or more and 35 wt% or less. If the content is less than 5 wt%, it is difficult to maintain sufficient skin permeability of the drug and long-term skin permeability. On the other hand, if it exceeds 35 wt%, the effect of improving the skin permeability of the drug is improved. As the fruits peak, they are less favorable from an economic point of view. In addition, when the patch is applied to the skin and peeled off, glue residue easily forms on the skin.
本発明 にお ける ア ク リ ル系粘着剤 と しては、 炭素数 2 〜 2 0 の (メ タ） ア ク リ ル酸アルキルエステルを主成分と し、 1 0 ％以 下の （メ タ） ア ク リ ル酸を含有する （メ タ） ア ク リ ル酸アルキルェ ステル共重合体が好ま しい。 かかる炭素数 2 〜 2 0 の （メ タ） ァ ク リ ル酸アルキルエステルと しては、 ェチル （メ タ） ァ ク リ レー ト 、 ブチル （メ タ） ァク リ レー ト 、 ペンチル （メ タ） ァ ク リ レー ト 、 へ キシル （メ タ） ァク リ レー ト 、 ヘプチル （メ タ） ァ ク リ レー ト 、 ォ クチル （メ タ） ァク リ レー ト 、 2 —ェチルへキシル （メ タ） ァ ク リ レー ト 、 ノ ニル （メ タ） ァ ク リ レー ト 、 へキサデシル （メ タ） ァ ク リ レー ト 、 及び ドデシル （メ タ） ァ ク リ レー ト な どがあげられる。 これ ら のなかで も、 特に 2 —ェチルへキシルァク リ レー ト を主成分 とする共重合体が粘着力の点か ら好ま しい。  The acryl-based pressure-sensitive adhesive in the present invention contains an alkyl (meth) acrylate having 2 to 20 carbon atoms as a main component, and has an (meth) acrylate of 10% or less. ) Acrylic acid-containing (meth) alkyl acrylate copolymers are preferred. Examples of the alkyl (meth) acrylate having 2 to 20 carbon atoms include ethyl (meth) acrylate, butyl (meth) acrylate, and pentyl (meta). ) Acrylate, hexyl (meta) acrylate, heptyl (meta) acrylate, octyl (meta) acrylate, 2-ethylhexyl (meta) ) Acrylate, nonyl (meta) acrylate, hexadecyl (meta) acrylate, and dodecyl (meta) acrylate. Among these, a copolymer containing 2-ethylhexyl acrylate as a main component is particularly preferred from the viewpoint of adhesive strength.
本発明において、 例えば上記の 「 （メ タ） ア ク リ ル酸アルキルェ ステル」 は、 ア ク リ ル酸アルキルエステルまたはメ タ ク リ ル酸アル キルエステルを意味する。  In the present invention, for example, the above-mentioned “(meth) alkyl acrylate” means an alkyl acrylate or an alkyl methacrylate.
また、 粘着力 を調整する 目 的で、 ア ク リ ル系粘着剤に酢酸 ビニル 系粘着剤、 シ リ コーン系粘着剤をア ク リ ル系粘着剤の等量未満で混 合してもよい。  In addition, for the purpose of adjusting the adhesive strength, an acrylic adhesive may be mixed with a vinyl acetate adhesive or a silicone adhesive in an amount less than the equivalent amount of the acrylic adhesive. .
本発明のエス ト ラ ジオールとは、 天然型卵胞ホルモンと合成卵胞 ホルモンおよびそれ ら の誘導体をいい、 例えば、 エス ト ラ ジオール 安息香酸エス 卜 ラ ジオール、 ジプロ ピオン酸エス ト ラ ジオール、 吉 草酸エス ト ラジオール、 及びェチニルエス トラジオール等があげら れる。 中でもエス ト ラジオールが好ましい。 The estradiol of the present invention refers to natural estrogen, synthetic estrogen, and derivatives thereof, for example, estradiol benzoate, estradiol benzoate, estradiol dipropionate, Estradiol valerate, ethynyl estradiol, and the like. Among them, estradiol is preferred.
本発明のェス ト ラジオニルの貼付剤中における含有量は、 0 . 4 w t %以上 2 . 5 w t %以下が好ま しく 、 特に好ま しく は 0 . 6 w t %以上 2 . 0 1 %以下である。 含有量が 0 . 4 w t %未満では 十分な量の薬物の皮膚透過性が得られにく い。 また、 含有量が 2 . 5 w t %を超える場合、 使用後の貼付剤の残存薬物量が増えるため 不経済である。  The content of the estradionil of the present invention in the patch is preferably 0.4 wt% or more and 2.5 wt% or less, particularly preferably 0.6 wt% or more and 2.01% or less. . If the content is less than 0.4 wt%, it is difficult to obtain a sufficient amount of the drug through the skin. On the other hand, if the content exceeds 2.5 wt%, it is uneconomical because the amount of residual drug in the patch after use increases.
薬物を該粘着剤層に含有させる方法と しては、 従来公知の方法を 採用する こ とができる。 例えば、 溶液状の粘着剤に薬物溶液をあ ら かじめ混合して薬物含有粘着剤層とする方法、 または薬物を含有し ないか又は薬物を十分には含有しない粘着剤層に、 含浸、 転着、 ま たはスプレー等によ り薬物を経皮吸収に十分な量含有させる方法等 である。  As a method for incorporating a drug into the pressure-sensitive adhesive layer, a conventionally known method can be employed. For example, a method in which a drug solution is preliminarily mixed with a solution-type pressure-sensitive adhesive to form a drug-containing pressure-sensitive adhesive layer, or a pressure-sensitive adhesive layer that does not contain a drug or does not sufficiently contain a drug is impregnated, inverted, or This is a method in which the drug is contained in a sufficient amount for transdermal absorption by wearing or spraying.
また本発明の粘着剤層中に、 粘着剤層の凝集力を向上させる 目的 で架橋を行う こ ともできる。 かかる架橋の方法と しては、 紫外線や ァ線などによる架橋、 あるいは無水ケィ酸、 ポリイ ソシァネー ト化 合物、 有機金属塩、 金属キレー ト化合物、 ポリ イオンコ ンプレッ ク ス形成可能な高分子などの架橋剤を添加して架橋する方法などを用 いる ことができる。  Crosslinking may be performed in the pressure-sensitive adhesive layer of the present invention for the purpose of improving the cohesive strength of the pressure-sensitive adhesive layer. Examples of such a cross-linking method include cross-linking by ultraviolet rays or ultraviolet rays, or the use of a polymer such as a caustic anhydride, a polyisocyanate compound, an organic metal salt, a metal chelate compound, or a polymer capable of forming a polyion complex. For example, a method of adding a crosslinking agent to perform crosslinking can be used.
更に本発明の粘着剤中に従来既知の安定化剤、 抗酸化剤、 香料、 防腐剤や P H調整剤などを必要に応じて添加する こ ともできる。 具 体的には、 例えばステア リ ン酸マグネシウム、 ステア リ ン酸亜鉛、 無水クェン酸などの安定化剤 ； 例えば、 ァスコルビン酸、 酢酸 ト コ フエロール、 ビタ ミ ン Eなどの抗酸化剤 ； 例えば、 メ ン トール、 力 ンフル、 ノヽッ力油、 レモン油などの香料 ； 例えば、 ジブチルヒ ド ロ キシ トルエン、 パラォキシ安息香酸イ ソブチルなどの防腐剤 ； 例え ばクェン酸ナ ト リ ウム、 クェン酸二水素ナ ト リ ウム、 リ ン酸水素ナ ト リ ウム、 リ ン酸水素ナ ト リ ウムなどの p H調整剤などをあげる こ とができる。 これらは単独でも、 1 種または 2種以上の混合系でも 使用できる。 Further, conventionally known stabilizers, antioxidants, fragrances, preservatives, pH adjusters, and the like can be added to the pressure-sensitive adhesive of the present invention as needed. Specifically, stabilizers such as magnesium stearate, zinc stearate, and citric anhydride; for example, ascorbic acid, toco acetate Antioxidants such as ferol and vitamin E; fragrances such as menthol, potato fulness, oil, lemon oil; preservatives such as dibutylhydroxytoluene and isobutyl paraoxybenzoate; For example, pH adjusters such as sodium citrate, sodium dihydrogen citrate, sodium hydrogen phosphite, sodium hydrogen phosphite and the like can be mentioned. These can be used alone or in combination of one or more.
本発明において用いられる支持体と しては、 粘着剤層を貼 り あわ せる こ とができ、 自己形状保持性を有しているものであればよ く 、 その材質や形状等に特に制限はない。 例えば、 ポリ エステル、 ポ リ ォレフィ ン、 ポリ塩化ビニル、 ポリ ウ レタ ン及びセルロースエステ ルなどのポリ マーフィ ルム ； ポリ エステル、 ポリ オレフイ ン、 ポリ ウ レタ ン、 セルロースエステル及びポリ アミ ド等,の繊維からなる織 物 · 編物 ' 不織布及び紙 ； ポリ エステル、 ポリ オレフイ ン、 セル口 —スエステル、 ポリ ウ レタ ン及びポリ アミ ド等からなる多孔性膜 ； 及びこれらの 2 種以上の組み合わせからなる積層体などから選ぶこ とができる。 該支持体の厚さは特に制限はないが、 5 0〜 1 0 0 0 mが取り扱い性の点から好ましい。  The support used in the present invention is not particularly limited as long as it can adhere an adhesive layer and has a self-shape retention property. The material and shape are not particularly limited. Absent. For example, polymer films such as polyester, polyolefin, polyvinyl chloride, polyurethane, and cellulose ester; fibers such as polyester, polyolefin, polyurethane, cellulose ester, and polyamide. Nonwoven fabrics and papers; porous membranes composed of polyester, polyolefin, cell mouth, polyester, polyurethane, polyamide, etc .; and laminates composed of a combination of two or more of these You can choose from such as. The thickness of the support is not particularly limited, but is preferably 50 to 100 m from the viewpoint of handleability.
本発明における粘着剤層の厚みは特に制限はないが、 1 0〜 3 0 0 mが好ましく 、 4 0〜 2 0 0 ΓΠが特に好ましい。  The thickness of the pressure-sensitive adhesive layer in the present invention is not particularly limited, but is preferably from 10 to 300 m, and particularly preferably from 40 to 200 m.
上述したよう に、 エス ト ラジオールとァク リ ル系粘着剤及び吸収 促進剤からなる粘着剤層が設けられた貼付剤において、 吸収促進剤 と して、 ソルビ夕 ンモノ ラウ レー ト及びポ リ エチレングリ コールモ ノ ラウ レー トか ら選ばれる一以上と、 室温で液状の高級脂肪酸エス テル及び炭化水素類から選ばれる一種以上との混合物を用いる こ と によ り 、 エス ト ラジオールの皮膚透過性に優れ、 かつ長時間にわた つて皮膚透過性が持続され、 また安全性や経済性にも優れた貼付剤 が得られる。 実施例 As described above, in a patch provided with an adhesive layer composed of estradiol, an acryl-based adhesive, and an absorption accelerator, sorbitan monolaurate and polyethylene are used as absorption accelerators. One or more selected from glycol monolaurate and higher fatty acid esters that are liquid at room temperature. By using a mixture with at least one selected from the group consisting of ether and hydrocarbons, it is possible to achieve excellent skin permeability of estradiol, maintain skin permeability for a long period of time, and be safe and economical. An excellent patch can be obtained. Example
以下に本発明を実施例によ り説明する。 なお、 実施例中、 部およ び％は、 それぞれ重量部および重量％を意味する。 また、 実施例中 の血液中薬物濃度は、 ヘラ レスラ ッ トに貼付剤を貼付し、 貼付後 7 時間、 2 4時間後に採血を行い、 血液中のエス ト ラジオールをラジ オイムノ アッセィにて定量した。 実施例 1  Hereinafter, the present invention will be described with reference to examples. In the examples, parts and% mean parts by weight and% by weight, respectively. The drug concentration in the blood in the examples was determined by applying a patch to a spatula plate, collecting blood 7 hours and 24 hours after application, and quantifying the amount of estradiol in the blood by radioimmunoassay. . Example 1
アク リ ル系粘着剤と して、 2 —ェチルへキシルァク リ レー ト 9 0 %、 メタアク リ ル酸メチル 7 %、 アク リ ル酸 3 %からなるポ リ ア ク リル酸アルキルエステル共重合体溶液 （固形分 1 5 % ) 2 4 . 3 部にエス ト ラジオールの 5 %アセ ト ン溶液 1 . 2 部、 ソルビタ ンモ ノ ラウ レー ト 0 . 2 5部、 ミ リ スチン酸イ ソプロ ピル 1 . 0 部、 架 橋剤と してポリ ビニルピロ リ ド ン 0 . 0 5 部、 酢酸ェチル 1 9 部、 エタノール 1 3 部を加えた。 次いでこれをシリ コーンコー ト した離 型フィ ルム上に乾燥後の粘着剤層の厚みが 7 0 となるよう に塗 ェし、 6 O t:で 3 0 分乾燥し、 次いで粘着剤層の片面に 1 2 mの P E Tフィ ルムを貼 り あわせて貼付剤を得た。 得られた貼付剤を Φ (直径） 2 7 m mに打ち抜いたものを体重約 1 4 0 gの除毛したへ アレスラ ッ トの背部に貼付した。 貼付後 7 時間、 2 4時間後に採血 を行い、 ラジオィムノ アッセィ にて血液中の薬物濃度を定量した。 結果を表 1 に示す。 表 1 に示すよ う に、 得られた貼付剤は高い薬物 吸収性を示した。 実施例 2 〜 8、 比較例 1 〜 2 Polyacrylic acid alkyl ester copolymer solution consisting of 90% 2-ethylhexyl acrylate, 7% methyl methacrylate, and 3% acrylic acid as an acrylic adhesive (Solid content: 15%) 24.3 parts: 1.2 parts of a 5% solution of estradiol in acetate, 0.2 part: sorbitan monolaurate: 0.25 parts, isopropyl myristate: 1.0 Parts, 0.05 parts of polyvinylpyrrolidone, 19 parts of ethyl acetate and 13 parts of ethanol were added as a crosslinking agent. Then, this is coated on a silicone-coated release film so that the dried adhesive layer has a thickness of 70, dried at 60 Ot: for 30 minutes, and then applied on one side of the adhesive layer. A 12 m PET film was stuck together to obtain a patch. The resulting patch was punched out to a diameter of 27 mm to remove hair with a weight of about 140 g. Affixed to the back of the Areslat. Blood was collected 7 hours and 24 hours after application, and the drug concentration in the blood was quantified by Radioimno Assay. Table 1 shows the results. As shown in Table 1, the obtained patch showed high drug absorption. Examples 2-8, Comparative Examples 1-2
表 1 に示す配合組成に変えた以外は実施例 1 と同様にして貼付剤 を得た。  A patch was obtained in the same manner as in Example 1 except that the composition shown in Table 1 was changed.
表 1 に示すよう に実施例 2 ~ 8 の貼付剤は長時間にわたって高い 薬物吸収性を示した。 これに対して、 比較例 1 、 2 のよう に、 吸収 促進剤と してソルビタンモノ ラウ レ一 トあるいはミ リ スチン酸ィ ソ プロ ピルを単独で用いた貼付剤は、 薬物の経皮吸収性が不十分であ つた。 As shown in Table 1, the patches of Examples 2 to 8 exhibited high drug absorption over a long period of time. On the other hand, as in Comparative Examples 1 and 2, patches using sorbitan monolaurate or isoisopropyl myristate alone as an absorption enhancer are not suitable for percutaneous absorption of drugs. Was insufficient.
実施例 1 実施例 2実施例 3実施例 4実施例 5実施例 6実施例 7実施例 8比較例 1 比較例 2 エストラジオール 1.2 1.2 0.8 1.2 1.2 1.8 1.2 1.2 1.2 1.2 アクリル系粘着剤 72.8 85.3 74.1 73.7 73.7 82.7 72.8 78.3 72.8 92.8 ソルビタンモノラウレー卜 5 2.5 5 5 5 5 5 ポリ才キシェチレンモノラウレー卜 5 5 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Comparative Example 1 Comparative Example 2 Estradiol 1.2 1.2 0.8 1.2 1.2 1.8 1.2 1.2 1.2 1.2 Acrylic adhesive 72.8 85.3 74.1 73.7 73.7 82.7 72.8 78.3 72.8 92.8 Sorbitan monolaurate 5 2.5 5 5 5 5 5 Poly-polykishetylene monolaurate 5 5
ミリスチン酸イソプロピル 20 10 5 5 10 5 25 Isopropyl myristate 20 10 5 5 10 5 25
才レイン酸ェチル 10 Ethyl oleate 10
スクヮラン 15 20 10 10 Squalane 15 20 10 10
流動パラフィン 15 Liquid paraffin 15
架橋剤 1 1 0.1 0.1 0.1 0.5 1 0.5 1 1 血液中薬物濃度 ： 貼付 7時間後 4168 3802 3959 4103 3756 6432 3929 4005 2183 1343 (pg/ml) ： 貼付 24時間後 1938 1462 2505 2342 1625 2362 1618 2156 960 812 Crosslinker 1 1 0.1 0.1 0.1 0.5 1 0.5 1 1 Blood drug concentration: 7 hours after application 4168 3802 3959 4103 3756 6432 3929 4005 2183 1343 (pg / ml): 24 hours after application 1938 1462 2505 2342 1625 2362 1618 2156 960 812

Claims

請求の範囲 The scope of the claims
1 . 柔軟な支持体の片面に薬物と吸収促進剤及び粘着剤を含有 する粘着剤層が設けられた貼付剤において、 1. In a patch in which an adhesive layer containing a drug, an absorption enhancer and an adhesive is provided on one side of a flexible support,
( 1 ) 該薬物が、 エス 卜ラジオールであ り、  (1) the drug is estradiol,
( i i ) 該吸収促進剤が、 ソルビ夕ンモノ ラウレー ト及びポリェ チレングリ コールモノ ラウレー 卜から選ばれる一以上と、 室温で液 状の高級脂肪酸エステル及び炭化水素類から選ばれる一種以上とか らなり、  (ii) the absorption enhancer comprises at least one selected from sorbitan monolaurate and polyethylene glycol monolaurate, and at least one selected from liquid higher fatty acid esters and hydrocarbons at room temperature;
( i i i ) 該粘着剤が、 アク リル系粘着剤である  (iii) the pressure-sensitive adhesive is an acrylic pressure-sensitive adhesive
貼付剤。 Patch.
2 . 該吸収促進剤において、 ソルビ夕ンモノ ラウレー ト及びポリ エチレングリ コールモノ ラウレ一 卜から選ばれる一以上の濃度が 2 w t %以上 1 0 ％以下であ り、 室温で液状の嵩級脂肪酸エステ ル及び炭化水素類から選ばれる一種以上の濃度が 5 w t %以上 3 5 w t %以下である請求の範囲第 1 項に記載の貼付剤。  2. In the absorption enhancer, the concentration of at least one selected from sorbitan monolaurate and polyethylene glycol monolaurate is 2 wt% to 10%, and the bulk fatty acid ester which is liquid at room temperature. 2. The patch according to claim 1, wherein the concentration of at least one selected from petroleum and hydrocarbons is 5 wt% or more and 35 wt% or less.
3 . 該室温で液状の高級脂肪酸エステルがミ リ スチン酸イ ソプロ ピルであり、 該炭化水素類が流動パラフィ ン及び Z又はスクヮラン である請求の範囲第 1 項または第 2項に記載の貼付剤。  3. The patch according to claim 1, wherein the higher fatty acid ester liquid at room temperature is isopropyl myristate, and the hydrocarbons are liquid paraffin and Z or squalane. .
4 . 該貼付剤中のエス ト ラジオールの濃度が 0 . 4 w t %以上 2 5 w t %以下であることを特徴とする請求の範囲第 1 項〜第 3項の いずれか一項に記載の貼付剤。 4. The patch according to any one of claims 1 to 3, wherein the concentration of estradiol in the patch is 0.4 wt% or more and 25 wt% or less. Agent.
PCT/JP2001/009915 2000-11-17 2001-11-13 Adhesive preparation containing estradiol WO2002040031A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
KR10-2003-7006318A KR100533493B1 (en) 2000-11-17 2001-11-13 Adhesive preparation containing estradiol
JP2002542404A JP3935839B2 (en) 2000-11-17 2001-11-13 Estradiol-containing patch
AU2002212763A AU2002212763A1 (en) 2000-11-17 2001-11-13 Adhesive preparation containing estradiol

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000-350657 2000-11-17
JP2000350657 2000-11-17

Publications (1)

Publication Number Publication Date
WO2002040031A1 true WO2002040031A1 (en) 2002-05-23

Family

ID=18823846

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Application Number Title Priority Date Filing Date
PCT/JP2001/009915 WO2002040031A1 (en) 2000-11-17 2001-11-13 Adhesive preparation containing estradiol

Country Status (5)

Country Link
JP (1) JP3935839B2 (en)
KR (1) KR100533493B1 (en)
CN (1) CN1198621C (en)
AU (1) AU2002212763A1 (en)
WO (1) WO2002040031A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006515617A (en) * 2003-01-03 2006-06-01 ディーピーシー プロダクツ， インコーポレイテッド Gilsonite-derived pharmaceutical delivery compositions and methods
JP2019210440A (en) * 2018-06-08 2019-12-12 株式会社日本触媒 Adhesive composition and use thereof

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0344326A (en) * 1989-07-10 1991-02-26 Sekisui Chem Co Ltd Percutaneous absorption preparation
JPH0344327A (en) * 1989-07-10 1991-02-26 Sekisui Chem Co Ltd Percutaneous absorption preparation
WO1996003131A1 (en) * 1994-07-22 1996-02-08 Sekisui Kagaku Kogyo Kabushiki Kaisha Percutaneously absorbable preparation
JPH09100227A (en) * 1989-09-08 1997-04-15 Cygnus Inc Solid matrix system for percutaneous drug delivery
JPH09315957A (en) * 1996-05-28 1997-12-09 Hisamitsu Pharmaceut Co Inc Device for percutaneous therapy
WO2000064418A2 (en) * 1999-04-22 2000-11-02 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system with neutralized acrylic adhesive patch

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0344326A (en) * 1989-07-10 1991-02-26 Sekisui Chem Co Ltd Percutaneous absorption preparation
JPH0344327A (en) * 1989-07-10 1991-02-26 Sekisui Chem Co Ltd Percutaneous absorption preparation
JPH09100227A (en) * 1989-09-08 1997-04-15 Cygnus Inc Solid matrix system for percutaneous drug delivery
WO1996003131A1 (en) * 1994-07-22 1996-02-08 Sekisui Kagaku Kogyo Kabushiki Kaisha Percutaneously absorbable preparation
JPH09315957A (en) * 1996-05-28 1997-12-09 Hisamitsu Pharmaceut Co Inc Device for percutaneous therapy
WO2000064418A2 (en) * 1999-04-22 2000-11-02 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system with neutralized acrylic adhesive patch

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006515617A (en) * 2003-01-03 2006-06-01 ディーピーシー プロダクツ， インコーポレイテッド Gilsonite-derived pharmaceutical delivery compositions and methods
JP2019210440A (en) * 2018-06-08 2019-12-12 株式会社日本触媒 Adhesive composition and use thereof
JP7112256B2 (en) 2018-06-08 2022-08-03 株式会社日本触媒 Adhesive composition and its use

Also Published As

Publication number Publication date
KR100533493B1 (en) 2005-12-06
JP3935839B2 (en) 2007-06-27
CN1198621C (en) 2005-04-27
JPWO2002040031A1 (en) 2004-03-18
CN1474695A (en) 2004-02-11
AU2002212763A1 (en) 2002-05-27
KR20040011430A (en) 2004-02-05

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