CN1228702A - 具有其中包括雌三醇的活性化合物联用的经皮治疗体系 - Google Patents
具有其中包括雌三醇的活性化合物联用的经皮治疗体系 Download PDFInfo
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- CN1228702A CN1228702A CN97197615A CN97197615A CN1228702A CN 1228702 A CN1228702 A CN 1228702A CN 97197615 A CN97197615 A CN 97197615A CN 97197615 A CN97197615 A CN 97197615A CN 1228702 A CN1228702 A CN 1228702A
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- Prior art keywords
- estriol
- transdermal therapeutic
- coupling
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- reactive compound
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- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
-
- 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
-
- 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
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
Abstract
本发明公开了一种将雌三醇作为活性物质的经皮治疗方法,其特征在于雌三醇与一种或多种活性物质联合使用。
Description
本发明涉及一种具有活性化合物联用(combination)的经皮治疗体系,在上述联用中包括雌三醇。
雌激素是甾族激素,可以四环C18-甾族雌烷得到。在天然雌激素中,雌酮、雌二醇和雌三醇是与众不同的,其中雌酮和雌三醇在生理学中被视为最重要的雌激素。雌三醇是雌二醇代谢的代谢终产物之一。
它具有一系列区别于其它雌激素的药物学和生物学特征:
即使在吸收前,其基本上已被完全结合。只有大约1-2%的雌三醇以在环境中游离的雌三醇形式出现。游离和结合雌三醇的比是1∶500。
当以2mg的剂量口服时,由于其与细胞核的受体结合仅会持续一小段时间,所以它在子宫内膜上不起增殖作用。但是只有当雌激素物质存留在核中相对较长的时间时,才会触发雌激素作用。只有当一天给服几次雌三醇时,这才是可能的。
雌三醇的另一个特殊的特征在于:连续服用雌三醇几个月时,雌激素的作用会增强。
阴道给药后,由于不发生肠代谢,所以血清中未结合的雌三醇高于口服给药后相应量的10到20倍。当以0.5mg的剂量阴道给药2小时后,可达到100-500pg/m的高血清浓度。作为对照,口服100mg的剂量时,才能达到同一样的效果。
从上述实验可以推断出:对于雌三醇,一种经皮治疗体系(TTS)是药物学上可选择的体系。通过该体系,可保证雌三醇在一段时间内,例如七天,连续地传递到身体各处。
到目前为止,人们认为活性化合物在替代治疗(HRT)方面的治疗活性不够。特别地,这种说法适用于雌三醇在预防骨质疏松症方面的应用。因此,在德国内分泌学学会的官方陈述中,特别强调了雌三醇不具有预防骨质疏松症的活性(参看:Deutsches Arzteblatt-Arztliche Mitteilungen,85,1322-1325,(1988))。
雌三醇在骨中不具有活性,这种概念已被引入相关课本中,成为标准常识(Freimut A.Leidenberger,“Klinische Endokrinologie fur Frauenarzte”Springer Verlag 1992,356页)。
雌三醇自身不具有在骨质疏松症治疗方面的活性还在产品制备信息中进一步被描出,在该制备信息中包括作为活性化合物的雌三醇(例如Jenapharm Medicaments:Range and Prices of 01.07.1991,67页)。
与此相反,以经皮治疗体系形式,单独使用雌三醇用于治疗骨质疏松症被披露于PCT申请WO93/18774中。据此,已有结果支持雌三醇可用作雌激素的选择,用于连续激素替代治疗,特别是用于治疗更年期骨质疏松症。一方面,连续给药可特别有效地治疗或预防骨质疏松症,另一方面没有出现常规雌激素的致癌作用,并且还期望其具有抗癌作用。
基于该有关医学知识的叙述,本发明的目的是说明显著改善的经皮治疗体系,该体系具有含雌三醇的活性化合物联用,该体系没有危险和有害的负作用,其在用于预防骨质疏松症、动脉硬化和/或老年心机能不全方面具有特别高的治疗功效和接受性(acceptance)。
令人惊奇的是,还发现经皮给药的雌三醇对经皮给药的二膦酸酯(biphosphonate)、β-阻滞剂和钙拮抗剂的效果有辅助作用,并且经皮给药的雌三醇与β-阻滞剂和钙拮抗剂联合使用时,可优选用于治疗动脉硬化或老年心机能不全。当与二膦酸酯联合时,适于通过经皮给药治疗骨质疏松症。
在其它应用中,还发现在治疗骨质疏松时,二膦酸酯与雌三醇联用通过经皮给药比单独使用雌三醇更有利。优选每个经皮治疗体系能在24小时内释放8-16mg雌三醇和3-7mg二膦酸酯的剂型。
根据本发明,适合于此的所有的经皮治疗体系都具有包括雌三醇的活性化合物,其能保证在至少24小时内连续释放活性化合物。使用合适的单个物质生产这种体系对本领域普通技术人员而言是已知的,并且在相关文献中有详细叙述。
Claims (7)
1.具有活性化合物雌三醇的经皮治疗体系,其特征在于它包括雌三醇与一种或多种其它活性化合物的联用。
2.根据权利要求1的经皮治疗体系,特征在于与雌三醇的联用中包括选自β-阻滞剂类或钙拮抗剂类的活性化合物。
3.根据权利要求1的经皮治疗体系,特征在于与雌三醇的联用中优选包含氨氯地平、卡维地洛、匹莫苯丹、噻吗洛尔、甲吲咯尔、维拉帕米、硝苯地平或尼莫地平。
4.根据权利要求1的经皮治疗体系,特征在于与雌三醇的联用中包含二膦酸酯。
5.根据权利要求4的雌三醇与二膦酸酯的经皮治疗体系中的活性化合物联用用于治疗骨质疏松症的应用。
6.根据权利要求2的雌三醇与选自β-阻滞剂类或钙拮抗剂类的经皮治疗体系中的活性化合物联用用于治疗老年心机能不全的应用。
7.根据权利要求2的雌三醇与选自β-阻滞剂类或钙拮抗剂结合的经皮治疗体系中的活性化合物联用用于治疗动脉硬化的应用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19635883.3 | 1996-09-04 | ||
DE19635883A DE19635883A1 (de) | 1996-09-04 | 1996-09-04 | Transdermales therapeutisches System mit einer Östriol enthaltenden Wirkstoffkombination |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1228702A true CN1228702A (zh) | 1999-09-15 |
Family
ID=7804611
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN97197615A Pending CN1228702A (zh) | 1996-09-04 | 1997-08-13 | 具有其中包括雌三醇的活性化合物联用的经皮治疗体系 |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP0927036B9 (zh) |
JP (1) | JP2000517324A (zh) |
KR (1) | KR20010029451A (zh) |
CN (1) | CN1228702A (zh) |
AT (1) | ATE289818T1 (zh) |
AU (1) | AU729898B2 (zh) |
CA (1) | CA2261655A1 (zh) |
CZ (1) | CZ70099A3 (zh) |
DE (2) | DE19635883A1 (zh) |
ES (1) | ES2239362T3 (zh) |
IL (1) | IL128768A0 (zh) |
NO (1) | NO991047D0 (zh) |
NZ (1) | NZ334443A (zh) |
PL (1) | PL332035A1 (zh) |
SK (1) | SK25299A3 (zh) |
WO (1) | WO1998009631A1 (zh) |
ZA (1) | ZA977895B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009075258A1 (ja) | 2007-12-10 | 2009-06-18 | Cosmed Pharmaceutical Co., Ltd. | 経皮吸収製剤 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5474783A (en) * | 1988-03-04 | 1995-12-12 | Noven Pharmaceuticals, Inc. | Solubility parameter based drug delivery system and method for altering drug saturation concentration |
US5656286A (en) * | 1988-03-04 | 1997-08-12 | Noven Pharmaceuticals, Inc. | Solubility parameter based drug delivery system and method for altering drug saturation concentration |
ATE119777T1 (de) * | 1991-02-26 | 1995-04-15 | Procter & Gamble Pharma | Behandlungsmethoden für osteoporose. |
ES2123666T3 (es) * | 1992-03-21 | 1999-01-16 | Entec | Aplicacion de estriol para la preparacion de un sistema terapeutico transdermico para tratar la osteoporosis climaterica. |
JPH0679002A (ja) * | 1993-12-14 | 1994-03-22 | Hisamitsu Pharmaceut Co Inc | 経皮投与用パッチシステム |
DE4405898A1 (de) * | 1994-02-18 | 1995-08-24 | Schering Ag | Transdermale therapeutische Systeme enthaltend Sexualsteroide |
-
1996
- 1996-09-04 DE DE19635883A patent/DE19635883A1/de not_active Withdrawn
-
1997
- 1997-08-13 EP EP97937573A patent/EP0927036B9/de not_active Expired - Lifetime
- 1997-08-13 JP JP10512160A patent/JP2000517324A/ja active Pending
- 1997-08-13 CZ CZ99700A patent/CZ70099A3/cs unknown
- 1997-08-13 PL PL97332035A patent/PL332035A1/xx unknown
- 1997-08-13 ES ES97937573T patent/ES2239362T3/es not_active Expired - Lifetime
- 1997-08-13 SK SK252-99A patent/SK25299A3/sk unknown
- 1997-08-13 NZ NZ334443A patent/NZ334443A/xx unknown
- 1997-08-13 KR KR1019997001714A patent/KR20010029451A/ko not_active Application Discontinuation
- 1997-08-13 AU AU40150/97A patent/AU729898B2/en not_active Ceased
- 1997-08-13 CN CN97197615A patent/CN1228702A/zh active Pending
- 1997-08-13 CA CA002261655A patent/CA2261655A1/en not_active Abandoned
- 1997-08-13 WO PCT/EP1997/004392 patent/WO1998009631A1/de not_active Application Discontinuation
- 1997-08-13 IL IL12876897A patent/IL128768A0/xx unknown
- 1997-08-13 DE DE59712215T patent/DE59712215D1/de not_active Expired - Lifetime
- 1997-08-13 AT AT97937573T patent/ATE289818T1/de not_active IP Right Cessation
- 1997-09-03 ZA ZA9707895A patent/ZA977895B/xx unknown
-
1999
- 1999-03-03 NO NO991047A patent/NO991047D0/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
NZ334443A (en) | 1999-08-30 |
ES2239362T3 (es) | 2005-09-16 |
EP0927036A1 (de) | 1999-07-07 |
KR20010029451A (ko) | 2001-04-06 |
ZA977895B (en) | 1998-03-02 |
EP0927036B1 (de) | 2005-03-02 |
DE19635883A1 (de) | 1998-03-05 |
ATE289818T1 (de) | 2005-03-15 |
IL128768A0 (en) | 2000-01-31 |
AU729898B2 (en) | 2001-02-15 |
DE59712215D1 (de) | 2005-04-07 |
NO991047L (no) | 1999-03-03 |
NO991047D0 (no) | 1999-03-03 |
JP2000517324A (ja) | 2000-12-26 |
CZ70099A3 (cs) | 1999-07-14 |
CA2261655A1 (en) | 1998-03-12 |
EP0927036B9 (de) | 2005-08-10 |
PL332035A1 (en) | 1999-08-16 |
AU4015097A (en) | 1998-03-26 |
SK25299A3 (en) | 2000-08-14 |
WO1998009631A1 (de) | 1998-03-12 |
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