CN1183723A - 睾酮的经皮给药治疗系统 - Google Patents

睾酮的经皮给药治疗系统 Download PDF

Info

Publication number
CN1183723A
CN1183723A CN96193748A CN96193748A CN1183723A CN 1183723 A CN1183723 A CN 1183723A CN 96193748 A CN96193748 A CN 96193748A CN 96193748 A CN96193748 A CN 96193748A CN 1183723 A CN1183723 A CN 1183723A
Authority
CN
China
Prior art keywords
active component
testosterone
carrier
reservoir
adhesive phase
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.)
Pending
Application number
CN96193748A
Other languages
English (en)
Inventor
维尔弗里德·费舍尔
丹尼尔·布拉赫尔
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.)
Hexal AG
Original Assignee
Hexal AG
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 Hexal AG filed Critical Hexal AG
Publication of CN1183723A publication Critical patent/CN1183723A/zh
Pending 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
    • A61K31/56—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
    • A61K31/568—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • 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
    • 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
    • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
    • 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
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • 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
    • A61P5/26—Androgens
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Reproductive Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Endocrinology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Gynecology & Obstetrics (AREA)
  • Nanotechnology (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Pregnancy & Childbirth (AREA)
  • Diabetes (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)

Abstract

本发明涉及睾酮或睾酮衍生物作为活性组分给药的经皮治疗系统。

Description

睾酮的经皮给药治疗系统
根据本领域目前的情况，睾酮和睾酮衍生物主要用于男性的激素替代治疗。除了原发的和继发的性机能减退之外，其他的适应症是精子减少、交媾不能和早泄。其用于男性骨质疏松的试验目前也有进展；参见，例如，Rapads et al.，Trends in Osteoporosis(骨质疏松的发展方向)，1(1989)1-9。
由于睾酮的一次通过效应(first-pass effect)很高，当它被口服给药时，效能大大降低。因此，在替代治疗中，要么以口服有效的酯给药，例如睾酮十一烷酸酯，要么以可注射的贮存制剂给药，例如睾酮庚酸酯和睾酮丙酸酯。
那些结果产生了数个有意义的研制开发经皮治疗系统(TTS)的出发点。使用这种系统，可以避免在口服给药方式中活性组分的高剂量，阻止了疼痛的注射并且其血液水平可以较好地得到调节，并能很好地与约一天的生理节律相匹配。
例如，US-A-4704282描述了一种具有一个载体薄膜(增强装置)，活性组分储蓄器和可除去的覆盖薄膜(释放衬垫)的经皮治疗系统。活性组分储蓄器可以是含水的或不含水的凝胶或聚合物材料的形式，其中的活性组分以一种浓度溶解于其中，这种浓度不高于活性组分在基体材料中的饱和浓度。该基体可以包括渗透增强剂。要给药的活性组分可以例如是睾酮。当然，如果在经皮治疗系统中的睾酮以少于饱和溶液的形式存在，要获得令人满意的血液水平，渗透增强剂的存在就是不可避免的了，参见WO-A-9210231，11页，33行。
US-A-4849224提议一种其活性组分储蓄器由载体薄膜(支承箔)和多孔膜形成的经皮治疗系统。该活性组分可以是睾酮或睾酮酯。除活性组分外，可提供渗透增强剂。当然，该已知系统的使用性主要是在活性组分储蓄器的限度内来考虑的，该储蓄器由载体薄膜的叠片和膜形成，借助粘合环粘附在皮肤上。由于粘合剂是以环状形式提供的，实际上是提供了一个窗口，通过该窗口，活性组分和渗透增强剂能经膜渗透到皮肤而渗透增强剂不与粘合剂进行不必要的接触，这是因为还提供了额外的环状密封元件用于保护该粘合剂。由于仅能在环状粘合剂区域获得有限的粘合，所以已知区域的尺寸受到了限制。
WO-A-9210231＝EP-A-0562041是基于US-A-4849224之现有技术的基础之上的，根据该发明，在皮肤上提供一粘合环用于经皮治疗系统的粘合；参见WO-A-9210231，13页，18/19行。或者，推荐一种位于储蓄器下方的底部粘合层(在储蓄器下方不相连的底部粘合层)和也有的储蓄器粘合剂涂层(储蓄器的粘合剂表层)。但是，由于根据现有技术，渗透增强剂的使用对睾酮的给药方式是不可缺少的，所以，如果粘合剂不是以环状形式提供的话，不清楚WO-A-9210231是如何防止渗透增强剂所不需要的渗透的。
WO-A-9503764，WO-A-9423707和US-A-5152997也描述了用于睾酮给药的经皮治疗系统，那些系统是储蓄器系统，其中，活性组分以低于饱和的形式存在，并且其中还提供了渗透加速剂。那些已知的教导对应于如WO-A-9210231(11页，33行)所讨论的现有技术。
基于本发明的问题是提供用于睾酮或睾酮衍生物给药的经皮治疗系统，该系统不需要使用渗透增强剂并能保证活性组分在血液中令人满意的水平。
为此目的，按本发明提议一种用于睾酮或睾酮衍生物作为活性组分给药的经皮治疗系统(TTS)，它具有
-载体薄膜(支承箔)，
-储蓄器，
-用于活性组分的醇类载体，
-用于使该系统与皮肤接触的粘合剂层，以及
-可除去的覆盖薄膜(释放衬垫)，其中
-该系统不包含渗透增强剂，
-活性组分以饱和的形式存在于活性组分的载体中，并且
-在储蓄器和粘合剂层之间提供了一层膜
-该膜不控制活性组分的释放，但粘合剂层控制活性组分的释放。
本发明是基于如下惊奇的观察结果的基础之上的，即，当活性组分以饱和的形式存在于活性组分的载体中时，活性组分在血液中令人满意的水平能够或者尤其能够达到，而WO-A-9210231要求活性组分处于不饱和状态。
按照本发明，作为睾酮衍生物使用的可以是睾酮酯，尤其是睾酮庚酸酯，睾酮环戊丙酸酯、睾酮丙酸酯或睾酮十一烷酸酯，或低烷基睾酮，尤其是甲基睾酮。
活性组分可以以与环糊精或环糊精衍生物、尤其是β-环糊精的复合物的形式存在。
所说的膜可以是聚乙烯或聚丙烯膜。
根据优选的实施方案，储蓄器由载体薄膜和膜形成。
根据本发明，用于活性组分的醇类载体可以是乙醇或低分子量一元醇，如异丙醇，或低分子量多元醇，例如丙二醇，或其混合物。
对于根据本发明的粘合剂层，可选用基于例如聚氨酯、异丁烯、聚乙烯醚、硅氧烷或丙烯酸酯的压敏耐醇类的粘合剂。
基于硅氧烷的粘合剂可以是基于两种主要组分的硅氧烷粘合剂：一种聚合物或粘合剂，尤其是聚硅氧烷，和粘性树脂。聚硅氧烷粘合剂通常与用于粘合剂的交联剂配制在一起，典型的是高分子量聚二有机硅氧烷，并且采用合适的有机溶剂与树脂一起产生一种三维的硅酸酯结构。该树脂与聚合物的混合物是改变聚硅氧烷粘合剂物理性质的最重要的因素；参见，例如，Sobieski et al.，″Silicone Pressure Sensitive Adhesives(硅氧烷压敏粘合剂)″，Handbook of Pressure Sensitive Adhesive Technology(压敏粘合技术手册)，2nd ed.，pp.508-517(D.Satas，ed.)，Van Nostrand Reinhold，NewYork(1989)。
合适的压敏硅氧烷粘合剂可以以商标BIO-PSA X7通过商业途径获得。
基于硅氧烷的压敏粘合剂进一步的实例是三甲基化的二氧化硅，它是经具有端基为三甲基甲硅烷氧基的聚二甲基硅氧烷处理过的。
基于丙烯酸酯的粘合剂可以是由各种丙烯酸衍生物组成的均聚物、共聚物或三元共聚物。
例如，该丙烯酸酯聚合物可以是丙烯酸和其他可共聚单体的一种或多种单体的聚合物。该丙烯酸酯聚合物也可以包含丙烯酸和/或甲基丙烯酸烷基酯和/或可共聚二级单体或具有官能团的单体的共聚物。所得到的丙烯酸酯聚合物的粘结性可通过改变加入作为单体的各种典型的单体的量而加以改变。通常情况下，该丙烯酸酯聚合物由至少50％(重量)的丙烯酸酯、甲基丙烯酸酯、丙烯酸烷基酯或甲基丙烯酸烷基酯、0-20％的与丙烯酸酯可共聚的官能化单体、和0-40％不同的单体组成。
以下给出的是丙烯酸酯单体，它们可以与丙烯酸、甲基丙烯酸、丙烯酸丁酯、甲基丙烯酸丁酯、丙烯酸己酯、甲基丙烯酸己酯、丙烯酸异辛酯、甲基丙烯酸异辛酯、丙烯酸2-乙基己酯、甲基丙烯酸2-乙基己酯、丙烯酸癸酯、甲基丙烯酸癸酯、丙烯酸十二烷基酯、甲基丙烯酸十二烷基酯、丙烯酸十三烷基酯和甲基丙烯酸十三烷基酯一起使用。
例如，可使用的与上述丙烯酸酯、甲基丙烯酸酯、丙烯酸烷基酯或甲基丙烯酸烷基酯可共聚合的官能化单体为，例如，丙烯酸、甲基丙烯酸、马来酸、马来酸酐、丙烯酸羟乙基酯、丙烯酸羟丙基酯、丙烯酰胺、二甲基丙烯酰胺、丙烯腈、丙烯酸二甲基氨基乙酯、甲基丙烯酸二甲基氨基乙酯、丙烯酸叔丁基氨基乙酯和甲基丙烯酸叔丁基氨基乙酯、丙烯酸甲氧基乙酯和甲基丙烯酸甲氧基乙酯。
适用于本发明的压敏丙烯酸酯的其他细节和实例描述在SatasHandbook of Pressure Sensitive Adhesive Technology″Acrylic Adhesive″(Satas压敏粘合技术手册″丙烯酸粘合剂″)，2nd ed.，pp.396-456(D.Satas，ed.)，Van Nostrand Reinhold，New York(1989)中。
合适的压敏丙烯酸酯可以通过商业途径获得。
本发明的经皮治疗系统可以另外包含α-生育酚或α-生育酚衍生物和/或增粘剂，如羟丙基纤维素。
下面通过附图和实施例对本发明进行更详细的说明。
根据图1，本发明的经皮治疗系统可以包括载体薄膜(支承箔)(1)，它可以是略微凸形的，并与膜(3)一起形成储蓄器(2)，膜(3)不控制活性组分的释放。按图1，涂于膜(3)的是一粘合剂层(5)，粘合剂层(5)控制活性组分的释放。该粘合剂层(5)再被覆盖薄膜(释放衬垫)(6)覆盖，在给药前除去该覆盖薄膜。根据该图，载体薄膜(1)可以提供一个位于粘合剂层(5)周缘区域的环形沿口(4)，并在接触区域密封膜(3)。
实施例
对于粘合剂层，所用的是基于硅氧烷的压敏粘合剂(已用具有端基为三甲基甲硅烷氧基的聚二甲基硅氧烷处理的三甲基化二氧化硅；干燥时，层的厚度约为35-45μm；单位表面积重量约为50-60g/m2)。用涂敷装置将PET覆盖薄膜(厚度约75μm；单位表面积重量约100g/m2)涂敷于硅氧烷粘合剂上。然后，在该涂敷的覆盖薄膜上层压一微孔聚乙烯膜或微孔聚丙烯膜(可热封的；厚度约50μm；单位表面积重量约为10g/m2)，以形成覆盖薄膜、粘合剂和膜的层压件。然后，用封合机(有熔接环)将该层压件熔接在聚酯的载体薄膜上(铝与聚烯烃密封层(可热封的)一起蒸汽化；厚度约为70μm)，熔接的方式是使得引入活性组分的缝隙得以保留。装填可装填的经皮治疗系统(TTS)，例如，使用Hamilton注射器或装有插管的管式泵(tube pump)，装填如下活性组分溶液：
每一个TTS的活性组分溶液的组成：
               mg/TTS睾酮               60.5696％乙醇           157.18丙二醇             48.11α-生育酚          56.78羟丙基纤维素       5.98共计               328.61储蓄器的装填体积   360μl活性组分溶液的密度 0.91285g/cm2储蓄器的装填量     328.6mg
装填后，熔接装填缝隙。借助一个打孔器，装填的经皮治疗系统穿孔输出。

Claims (8)

1、一种用于睾酮或睾酮衍生物作为活性组分给药的经皮治疗系统(TTS)，它具有
-载体薄膜(支承箔)，
-储蓄器，
-用于活性组分的醇类载体，
-用于使该系统与皮肤接触的粘合剂层，以及
-可除去的覆盖薄膜(释放衬垫)，其中
-该系统不包含渗透增强剂，
-活性组分以饱和的形式存在于活性组分的载体中，并且
-在储蓄器和粘合剂层之间提供了一层膜，该膜不控制活性组分的释放，但粘合剂层控制活性组分的释放。
2、如权利要求1的系统，其特征在于，睾酮酯，尤其是睾酮庚酸酯，睾酮环戊丙酸酯、睾酮丙酸酯或睾酮十一烷酸酯，或低烷基睾酮，尤其是甲基睾酮作为睾酮衍生物。
3、如权利要求1或2的系统，其特征在于，所述的活性组分以与环糊精或环糊精衍生物，尤其是β-环糊精的复合物的形式存在。
4、如前述任何一项权利要求的系统，其特征在于，该储蓄器是由载体薄膜和膜形成的。
5、如前述任何一项权利要求的系统，其特征在于，乙醇或低分子量的一元醇或多元醇，尤其是丙二醇，或其混合物，作为活性组分的醇类载体。
6、如前述任何一项权利要求的系统，其特征在于，粘合剂层的粘合剂是压敏的、耐醇类的、基于聚氨酯、异丁烯、聚乙烯醚、硅氧烷或丙烯酸酯的粘合剂。
7、如前述任何一项权利要求的系统，其特征在于，活性组成的载体还包含α-生育酚或α-生育酚衍生物。
8、如前述任何一项权利要求的系统，其特征在于，活性组分的载体还包含增粘剂，如羟丙基纤维素。
CN96193748A 1995-05-10 1996-05-10 睾酮的经皮给药治疗系统 Pending CN1183723A (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19517145.4 1995-05-10
DE19517145A DE19517145C2 (de) 1995-05-10 1995-05-10 Transdermales therapeutisches System (TTS) zur Verabreichung von Testosteron

Publications (1)

Publication Number Publication Date
CN1183723A true CN1183723A (zh) 1998-06-03

Family

ID=7761562

Family Applications (1)

Application Number Title Priority Date Filing Date
CN96193748A Pending CN1183723A (zh) 1995-05-10 1996-05-10 睾酮的经皮给药治疗系统

Country Status (17)

Country Link
EP (1) EP0825865B1 (zh)
JP (1) JPH11504643A (zh)
CN (1) CN1183723A (zh)
AT (1) ATE208200T1 (zh)
AU (1) AU702710B2 (zh)
BR (1) BR9608255A (zh)
CA (1) CA2220358A1 (zh)
CZ (1) CZ287678B6 (zh)
DE (2) DE19517145C2 (zh)
DK (1) DK0825865T3 (zh)
HU (1) HUP9801130A3 (zh)
NO (1) NO975140L (zh)
NZ (1) NZ308516A (zh)
PL (1) PL323145A1 (zh)
SK (1) SK149797A3 (zh)
WO (1) WO1996035427A1 (zh)
ZA (1) ZA963743B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101480399B (zh) * 2008-09-25 2011-10-05 宋博 睾酮在制备治疗弱精子症的药物中的应用

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU1429697A (en) * 1995-12-29 1997-07-28 Cygnus, Inc. Systems and methods for the transdermal administration of androgenic agents
CA2259407C (en) * 1996-07-03 2006-04-04 Alza Corporation Drug delivery devices and process of manufacture
US6007837A (en) * 1996-07-03 1999-12-28 Alza Corporation Drug delivery devices and process of manufacture
DE19646050A1 (de) * 1996-11-08 1998-05-14 Labtec Gmbh Transdermales System mit einem speziellen Süßstoff zur Erhöhung der transdermalen Bioverfügbarkeit
US6174545B1 (en) 1997-07-01 2001-01-16 Alza Corporation Drug delivery devices and process of manufacture
EP1079815B1 (de) * 1998-05-22 2004-10-20 Novosis AG Zeitgesteuert freisetzende wirkstoffhaltige transdermalsysteme
FR2793689B1 (fr) * 1999-05-19 2001-08-24 Pf Medicament Dispositif transdermique pour l'administration de testosterone ou d'un de ses derives
US6503894B1 (en) 2000-08-30 2003-01-07 Unimed Pharmaceuticals, Inc. Pharmaceutical composition and method for treating hypogonadism
EP1611882B1 (en) 2004-06-01 2010-04-07 Hisamitsu Pharmaceutical Co., Inc. Adhesive patch
SI1937276T1 (sl) 2005-10-12 2013-04-30 Unimed Pharmaceuticals, Llc C/O Abbott Laboratoires 100 Abbott Park Road Izboljšani testosteronski gel in postopek uporabe
FR2895679B1 (fr) * 2005-12-29 2012-06-08 Pf Medicament Stabilisation de testosterone au sein de dispositifs transdermiques
DE102011012712A1 (de) 2011-03-01 2012-09-06 Frank Lehmann-Horn Verwendung von Aldosteron-Rezeptor-Antagonisten zur Behandlung von weiblicher sexueller Dysfunktion

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4286592A (en) * 1980-02-04 1981-09-01 Alza Corporation Therapeutic system for administering drugs to the skin
US4725439A (en) * 1984-06-29 1988-02-16 Alza Corporation Transdermal drug delivery device
US4704282A (en) * 1984-06-29 1987-11-03 Alza Corporation Transdermal therapeutic system having improved delivery characteristics
US4849224A (en) * 1987-11-12 1989-07-18 Theratech Inc. Device for administering an active agent to the skin or mucosa
GB8804164D0 (en) * 1988-02-23 1988-03-23 Tucker J M Bandage for administering physiologically active compound
US5474783A (en) * 1988-03-04 1995-12-12 Noven Pharmaceuticals, Inc. Solubility parameter based drug delivery system and method for altering drug saturation concentration
US5152997A (en) * 1990-12-11 1992-10-06 Theratech, Inc. Method and device for transdermally administering testosterone across nonscrotal skin at therapeutically effective levels
MX9202350A (es) * 1991-05-20 1992-11-01 Alza Corp Composiciones de incrementador de penetracion a la piel que usan monolinoleato de glicerol.
CA2075517C (en) * 1992-04-01 1997-03-11 John Wick Transdermal patch incorporating a polymer film incorporated with an active agent
AU677206B2 (en) * 1992-06-11 1997-04-17 Theratech, Inc. The use of glycerin in moderating transdermal drug delivery
EP0695177B1 (de) * 1993-04-20 1998-02-18 Hexal Ag Wirkstoffplaster
DE4313402A1 (de) * 1993-04-23 1994-10-27 Hexal Pharma Gmbh Transdermale Wirkstoffzubereitung
US5460820B1 (en) * 1993-08-03 1999-08-03 Theratech Inc Method for providing testosterone and optionally estrogen replacement therapy to women

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101480399B (zh) * 2008-09-25 2011-10-05 宋博 睾酮在制备治疗弱精子症的药物中的应用

Also Published As

Publication number Publication date
PL323145A1 (en) 1998-03-16
CA2220358A1 (en) 1996-11-14
AU702710B2 (en) 1999-03-04
JPH11504643A (ja) 1999-04-27
SK149797A3 (en) 1998-05-06
AU5805096A (en) 1996-11-29
HUP9801130A3 (en) 2001-03-28
DE19517145C2 (de) 2000-02-24
NZ308516A (en) 1999-05-28
NO975140L (no) 1997-11-10
HUP9801130A2 (hu) 1998-08-28
CZ287678B6 (en) 2001-01-17
DK0825865T3 (da) 2002-02-18
EP0825865B1 (de) 2001-11-07
ATE208200T1 (de) 2001-11-15
EP0825865A1 (de) 1998-03-04
DE19517145C1 (de) 1996-11-28
DE59608150D1 (de) 2001-12-13
ZA963743B (en) 1996-11-18
NO975140D0 (no) 1997-11-07
CZ351297A3 (cs) 1998-03-18
BR9608255A (pt) 1999-02-02
WO1996035427A1 (de) 1996-11-14

Similar Documents

Publication Publication Date Title
US10709669B2 (en) Microreservoir system based on polysiloxanes and ambiphilic solvents
CN1183723A (zh) 睾酮的经皮给药治疗系统
AU714798B2 (en) Drug delivery device
EP1163902B1 (en) Transdermal preparation containing hydrophilic or salt-form drug
JP5016309B2 (ja) 医療用テープ剤
US20150246006A1 (en) Transdermal systems having control delivery system
JPH07138153A (ja) 有効薬剤の経皮供給
KR20090049597A (ko) 첩부제
KR101942677B1 (ko) 첩부제
JP2004010525A (ja) 経皮吸収型製剤およびその製造方法
JP2003313122A (ja) ビソプロロール含有貼付剤
KR950014444B1 (ko) 니트로글리세린의 경피 투여형 약제
JP4081139B2 (ja) 酸に不安定な薬物の経皮送達のための組成物および方法
US7964213B2 (en) Patch and production method thereof
EP1802665A1 (en) Method for the manufacture of pressure sensitive adhesives
JPH09500129A (ja) 経皮メラトニン・デリバリー・システム
US5614210A (en) Transdermal device for the delivery of alfuzosin
KR20090051191A (ko) 첩부제
JPH0543457A (ja) 経皮吸収製剤
JPH07309755A (ja) 抗真菌薬貼付剤
JP2003073263A (ja) 安定性が改良された貼付剤
JP3233705B2 (ja) 貼付剤
JP2681375B2 (ja) 治療用接着製剤
JPH05148141A (ja) 経皮吸収製剤
JPS61221118A (ja) 医薬製剤

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication
REG Reference to a national code

Ref country code: HK

Ref legal event code: WD

Ref document number: 1018200

Country of ref document: HK