[go: up one dir, main page]

WO2008037176A1 - Préparations transdermiques comprenant de l'artémisinine et/ou ses dérivés - Google Patents

Préparations transdermiques comprenant de l'artémisinine et/ou ses dérivés Download PDF

Info

Publication number
WO2008037176A1
WO2008037176A1 PCT/CN2007/002661 CN2007002661W WO2008037176A1 WO 2008037176 A1 WO2008037176 A1 WO 2008037176A1 CN 2007002661 W CN2007002661 W CN 2007002661W WO 2008037176 A1 WO2008037176 A1 WO 2008037176A1
Authority
WO
WIPO (PCT)
Prior art keywords
weight
artemisinin
derivative
preparation
transdermal administration
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/CN2007/002661
Other languages
English (en)
Chinese (zh)
Inventor
Zuguang Ye
Naijie Wang
Zhihui Zhang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beijing Zhongyan Tongrentang Chinese Medicine R & D Co Ltd
Original Assignee
Beijing Zhongyan Tongrentang Chinese Medicine R & D 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 Beijing Zhongyan Tongrentang Chinese Medicine R & D Co Ltd filed Critical Beijing Zhongyan Tongrentang Chinese Medicine R & D Co Ltd
Publication of WO2008037176A1 publication Critical patent/WO2008037176A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • 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
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention belongs to the field of medical technology and relates to a preparation for transdermal administration containing artemisinin and/or a derivative thereof. ⁇ Background technique ⁇
  • Artemisinin and/or its derivatives are potent antimalarial drugs commonly used in clinical practice. Artemisinin and/or its derivatives have excellent antibacterial properties when Plasmodium is highly resistant to chloroquine, fascin and other drugs. Anti-malarial effect, and has a good therapeutic effect on falciparum malaria such as cerebral malaria, and without any side effects, it is an ideal fast-acting, low-toxic malaria treatment.
  • artemisinin and/or its derivatives especially artemisinin, have a first-pass effect on the liver when administered orally in tablets or capsules.
  • the pharmacist tries to give the suppository a rectum.
  • the method of administration of drugs and injections Although rectal administration and administration can avoid the first-pass effect, since artemisinin or its derivative has a short half-life, there is still a phenomenon in which the malaria parasite is easily re-ignited.
  • the present inventors have developed a therapeutic system for the preparation of an artemisinin and/or a derivative thereof by using artemisinin and/or a derivative thereof as an active ingredient. Absorption, avoiding first-pass effects, maintaining effective blood concentration for a long time, successfully solved the re-ignition problem of malaria parasites.
  • An object of the present invention is to provide a transdermal administration preparation containing artemisinin and/or a derivative thereof, which can absorb artemisinin and/or its derivative into the blood through the skin and maintain an effective effect. Blood concentration can prevent and reduce the re-ignition rate of Plasmodium.
  • the transdermal administration preparation containing artemisinin and/or a derivative thereof of the present invention comprises artemisinin and/or a derivative thereof, a substrate, a latent solvent, a transdermal absorption enhancer, and other additives.
  • the amount of each component is:
  • the main component capable of producing Plasmodium falciparum in the present invention is artemisinin and/or a derivative thereof, and the derivative of artemisinin
  • the organism is artemether, dihydroartemisinin, artesunate or other artemisinin derivatives, which are potent antimalarials that are used orally in the clinic for a long time.
  • artemisinin and/or its derivative is used in an amount of 0.1 to 40% by weight, preferably in an amount of 5.6 to 25% by weight.
  • the transdermal therapeutic system is prepared into a ointment, a patch, an elixir, a gel, a cataplasm, a coating agent, an elixir, using a water-soluble, water-emulsion, fat-soluble matrix.
  • External preparations such as paints and aerosols, especially those prepared by acrylate pressure sensitive adhesives, are preferred.
  • Acrylate polymers, polyisobutylene, and silicone pressure sensitive adhesives have been used since the 1960s for the preparation of medical tapes. It is very irritating to the skin itself, does not require the addition of tackifiers, antioxidants, and rarely causes allergic reactions.
  • the matrix used in the present invention has been included in the Handbook of Pharmaceutical Excipients of the United States and has high safety.
  • the amount of the substrate is suitably from 0.5 to 99.4% by weight, preferably in an amount of
  • the weight of the patch is more preferably from 50 to 70% by weight, and the amount of the ointment is more preferably from 0.5 to 88.9% by weight.
  • the water-soluble matrix may be carbomer, gelatin, cellulose derivative, glycerin, polyacrylic acid, sodium polyacrylate, poloxamer, polyethylene glycol, etc.; the water emulsion 'f raw matrix may be water-based acrylate Pressure sensitive adhesive, water emulsion ointment base, etc.; fat soluble matrix may be solvent type acrylate pressure sensitive adhesive, hot melt acrylate pressure sensitive adhesive, polyisobutylene pressure sensitive adhesive, silicone pressure sensitive adhesive, petrolatum, lanolin , beeswax, mixed fatty acid glycerides, etc.
  • artemisinin and/or a derivative thereof is a main component for producing a pharmacological effect.
  • the molecular formula of artemisinin is
  • artemisinin is colorless needle crystal, melting point is 156 ⁇ 157 °C. Soluble in chloroform, acetone, ethyl acetate and benzene, soluble in ethanol, ether, slightly soluble in cold petroleum ether, almost insoluble in water.
  • Artemether is a white crystal or crystalline powder, very soluble in acetone or chloroform, soluble in ethanol or ethyl acetate, almost insoluble in water, melting point 86 ⁇ 90 °C.
  • Dihydroartemisinin is white needle crystal, molecular formula: C 15 H 24 0 5 , molecular weight:
  • the present invention designs water, ethanol, glycerin, propylene glycol, polyethylene glycol 300, polyethylene glycol 400 and the like as potential solvents, and these materials and polymers
  • the acrylate polymer, polyisobutylene, silicone pressure-sensitive adhesive, and artemisinin and/or a derivative thereof are mixed, and after coating drying, artemisinin and/or a derivative thereof is uniformly distributed in a matrix in a dissolved or dispersed state.
  • One or more latent solvents may be used in the present invention.
  • the latent solvent is used in the present invention in an amount of from 0 to 98.4% by weight, preferably from 1.5 to 81.2% by weight.
  • a transdermal absorption enhancer is preferably added.
  • the main component of the present invention artemisinin and/or its derivative, must be absorbed through the skin and enter the blood circulation.
  • the stratum corneum of the human skin is a natural barrier for the drug to enter the body through the skin. In general, the drug is difficult to penetrate the skin.
  • Transdermal enhancer can greatly improve the transdermal drug The amount of absorption produces a good therapeutic effect.
  • the transdermal absorption enhancer may be selected from the group consisting of azone, oleic acid, urea,
  • the dermal, higher fatty acid, N-methylpyrrolidone, higher fatty acid ester and other promoting substances are used in the present invention in an amount of from 0 to 50.0% by weight, preferably from 4 to 10% by weight.
  • Artemisinin and/or its derivatives are easy to precipitate crystals from the matrix.
  • the present invention designs other polymer materials such as PVP, PEG, and acrylic resin as other additives, and these polymer materials and polymer acrylates.
  • the polymer, polyisobutylene, silicone pressure-sensitive adhesive, and artemisinin and/or a derivative thereof are mixed, and after coating and drying, crystallization can be suppressed.
  • Other polymer materials such as PVP, PEG, acrylic resin and the like are used in an amount of from 0 to 30% by weight, preferably from 0 to 15% by weight, more preferably from 0 to 10% by weight.
  • the components of the transdermal formulation are: artemisinin 8% by weight, acrylate pressure sensitive adhesive 78% by weight, PEG 400 10% by weight and azone a 4% by weight.
  • the components of the transdermal formulation are 19% by weight of artemether, 76% by weight of acrylate pressure sensitive adhesive and 5% by weight of N-methylpyrrolidone.
  • the components of the transdermal formulation are: dihydroartemisinin 5.6 % by weight, polyisobutylene pressure sensitive adhesive 88.9% by weight and oleic acid 5.5 % by weight.
  • the components of the transdermal formulation are: artesunate 14.8% by weight, acrylate pressure sensitive adhesive 79.2% by weight and propylene glycol 1.5% by weight and azone 4.5% by weight.
  • the components of the transdermal formulation are: 10.6% by weight of artemisinin, 84.6% by weight of a fat-soluble ointment base and 4.5% by weight of azone.
  • the components of the transdermal formulation are: dihydroartemisinin 10% by weight, water 81.2% by weight, carbomer 4.2% by weight, and oleic acid 4.6% by weight.
  • the components of the transdermal formulation are: 12.8% by weight of artemisinin, 51.4% by weight of acrylate pressure sensitive adhesive, 25.6% by weight of PEG 400, 3.8% by weight of azone, and oleic acid. 6.4% weight
  • the components of the transdermal formulation are: artemether 25 % by weight, acrylate pressure sensitive adhesive 68% by weight and N-methylpyrrolidone 7% by weight.
  • the components of the transdermal formulation are: artesunate 25% by weight, acrylate pressure sensitive adhesive 55 % by weight, PVP K30 10% by weight and oleic acid 10% by weight.
  • the components of the transdermal formulation are: artemisinin 10% by weight, PEG 400 54.8% by weight, poloxamer 27.2% by weight, azone 3% by weight, and oleic acid 5 %weight.
  • the components of the transdermal formulation are: artemisinin 10% by weight, 66.5% by weight of water, 0.5% by weight of carbomer, 3% by weight of N-methylpyrrolidone and 20% by weight of PEG400.
  • the components of the transdermal formulation are: 16% by weight of artemether, 80% by weight of acrylate pressure sensitive adhesive, 3% by weight of propylene glycol and 1% by weight of azone.
  • the transdermal therapeutic system of artemisinin and/or its derivative of the present invention is prepared by using the main component artemisinin and/or a derivative thereof, a latent solvent such as glycerin, ethanol, polyethylene glycol 300, polyethylene glycol.
  • a latent solvent such as glycerin, ethanol, polyethylene glycol 300, polyethylene glycol.
  • water-soluble, water-milk, fat-soluble matrix and transdermal enhancers such as azone, oleic acid, urea, DMSO, higher fatty acids, N-methylpyrrolidone, higher fatty acid esters and other promoting substances
  • additives are thoroughly mixed and prepared into an ointment, a patch, an elixir, a gel, a cataplasm, a coating agent, an elixir, a coating agent, an aerosol, and the like, and the artemisinin and/or its derivative are percutaneously administered.
  • Drug preparation system such as water-soluble, water-milk, fat-soluble matrix and transdermal enhancers such as azone, oleic acid, urea, DMSO, higher fatty acids, N-methylpyrrolidone, higher fatty acid esters and other promoting substances
  • other additives are thoroughly mixed and prepared into an ointment, a patch, an elixir, a gel, a cataplasm,
  • the transdermal formulation of artemisinin and/or its derivatives of the present invention is used for the conversion of malaria parasites, prevention and reduction of re-ignition of malaria parasites, and treatment of other parasitic diseases.
  • the preparation of the artemisinin and/or its derivative prepared by the invention has been tested by pharmacodynamic test, and the result proves that the preparation for transdermal administration has excellent antimalarial effect and no adverse reaction, and the test group has malaria parasites. Both turned negative and basically solved the problem of re-ignition of malaria parasites. . ,
  • 150 g of artesunate was dissolved in 800 g of acrylate pressure-sensitive adhesive, 45 g of azone and 15 g of propylene glycol were added, mixed uniformly, coated on a backing with a coater, dried, and composited with a protective film, and punched and obtained.
  • Dissolve 150g of artesunate in 800g of acrylate pressure sensitive adhesive add 50g of oleic acid, 50g of PVP K30, mix evenly, apply it on the backing with a coater, dry, compound with protective film, punch and cut .
  • 80 g of artemisinin, 40 g of oleic acid, 24 g of azone, 440 g of PEG400, and poloxamer are dissolved in 220 g, and mixed at 60 ° C, and allowed to cool.
  • 60 g of artemether was dissolved in 800 g of acrylate pressure sensitive adhesive, 11.4 g of propylene glycol, 3.8 g of azone, and mixed, and coated on a backing with a coater, dried, and compounded with a protective film. .
  • ICR mice weighing 21-23 g, male. Randomly grouped into 9 groups according to body weight, model control group, oral artemisinin group, artemisinin transdermal drug group, oral artemether group, artemether percutaneous drug group, oral dihydroartemisinin group, double Hydrogen artemisinin transdermal drug group, oral artesunate, artesunate transdermal drug group, 10 rats in each group, depilatory hair removal on the back skin of mice one day in advance, intraperitoneal dosing in the next day Containing 10 million red blood cells infected with Plasmodium falciparum, inoculated with 0.2 ml/only, each group of artemisinin and / or its derivatives were administered transdermally, inoculated on the day of the mice Dosage of the back skin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

La présente invention concerne des préparations transdermiques pour le traitement de paludisme comprenant de l'artémisinine et/ou ses dérivés, des matrices, des cosolvants, des activateurs de pénétration et d'autres additifs.
PCT/CN2007/002661 2006-09-29 2007-09-06 Préparations transdermiques comprenant de l'artémisinine et/ou ses dérivés Ceased WO2008037176A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2006101528000A CN101152162B (zh) 2006-09-29 2006-09-29 一种含青蒿素或其衍生物的经皮给药制剂及其制药用途
CN200610152800.0 2006-09-29

Publications (1)

Publication Number Publication Date
WO2008037176A1 true WO2008037176A1 (fr) 2008-04-03

Family

ID=39229729

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2007/002661 Ceased WO2008037176A1 (fr) 2006-09-29 2007-09-06 Préparations transdermiques comprenant de l'artémisinine et/ou ses dérivés

Country Status (2)

Country Link
CN (1) CN101152162B (fr)
WO (1) WO2008037176A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220211698A1 (en) * 2020-11-17 2022-07-07 Instituto De Medicina Molecular Anti malarial compounds

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103450468B (zh) * 2012-05-30 2016-06-15 北京凯正生物工程发展有限责任公司 青蒿琥酯聚乙二醇化衍生物、其药物组合物及其用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995034262A1 (fr) * 1994-06-16 1995-12-21 Department Of The Army, Us Government Traitement transdermique du paludisme
CN1602858A (zh) * 2003-09-30 2005-04-06 昆明紫健生物技术有限公司 治疗妇科疾病的青蒿素制剂

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1186661A (zh) * 1996-12-30 1998-07-08 中国科学院上海药物研究所 青蒿素衍生物的新组合物及其应用
CN1650854A (zh) * 2004-12-08 2005-08-10 广州中生生物技术有限公司 一种含有蒿甲醚（或蒿乙醚或蒿琥酯）微乳剂的制备工艺

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995034262A1 (fr) * 1994-06-16 1995-12-21 Department Of The Army, Us Government Traitement transdermique du paludisme
CN1602858A (zh) * 2003-09-30 2005-04-06 昆明紫健生物技术有限公司 治疗妇科疾病的青蒿素制剂

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SUN GUOQING ET AL.: "Effect of Penetration Enhancers on the vitro Permeability of Artesunate through Excised Mouse Skin", JOURNAL OF CHINA PHARMACEUTICAL UNIVERSITY, vol. 27, no. 6, 1996, pages 345 - 349 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220211698A1 (en) * 2020-11-17 2022-07-07 Instituto De Medicina Molecular Anti malarial compounds

Also Published As

Publication number Publication date
CN101152162A (zh) 2008-04-02
CN101152162B (zh) 2011-05-11

Similar Documents

Publication Publication Date Title
CA2667477C (fr) Administration transdermique de derives polaires de ketoprofene
ES2785992T3 (es) Sistema de administración de fármacos transdérmico que contiene donepezil
TWI635876B (zh) 含有利凡斯的明（ｒｉｖａｓｔｉｇｍｉｎｅ）的經皮藥物傳輸系統
JP2019501215A (ja) 局所皮膜形成スプレー
WO2007120868A2 (fr) Amélioration de la biodisponibilité d'un médicament lipophile à l'aide d'un système de solvants
CN102413821A (zh) 经皮吸收型制剂
ES2504065T3 (es) Composición estable de rasagilina
WO2005077364A1 (fr) Préparation transdermique de solifénacine et procédé d'amélioration de la perméabilité transdermique de celle-ci
WO2008037176A1 (fr) Préparations transdermiques comprenant de l'artémisinine et/ou ses dérivés
CA2926146C (fr) Nouvelle formulation
JP5632577B2 (ja) 貼付剤
JPS62148422A (ja) 治療システム
JP7354242B2 (ja) イブプロフェンまたはその構造類似体を含む多層経皮薬物送達システム
KR20020068385A (ko) 소양증 치료용 외용제
JPH0572368B2 (fr)
WO2014159748A1 (fr) Système d'administration de médicament transdermique contenant du donépézil
US20070254887A1 (en) Pharmaceutical Composition for Transdermal Administration of Perospirone
KR20200006065A (ko) 루파타딘-함유 패치
JP2003119132A (ja) トラニラスト経皮吸収貼付剤
JPH0627074B2 (ja) 医薬組成物
KR100552651B1 (ko) 비스테로이드성 소염진통제 함유 플라스터
US20140370077A1 (en) Transdermal drug delivery system containing fentanyl
WO2005077380A1 (fr) Preparation externe pour traiter les plaies cutanees douloureuses
JPH0930972A (ja) オキサトミド含有経皮適用製剤
JP3203056B2 (ja) メシル酸ベタヒスチンの経皮吸収製剤用組成物および経皮吸収製剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07800877

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07800877

Country of ref document: EP

Kind code of ref document: A1