CN1665516A - 使用依西美坦治疗不孕症 - Google Patents
使用依西美坦治疗不孕症 Download PDFInfo
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- CN1665516A CN1665516A CN038157306A CN03815730A CN1665516A CN 1665516 A CN1665516 A CN 1665516A CN 038157306 A CN038157306 A CN 038157306A CN 03815730 A CN03815730 A CN 03815730A CN 1665516 A CN1665516 A CN 1665516A
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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
- 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
- A61K31/5685—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 having an oxo group in position 17, e.g. androsterone
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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
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- 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
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- 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
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Abstract
本发明提供一种治疗雌性宿主不孕症的方法,其包含施用刺激卵巢卵泡有效量的依西美坦。
Description
发明领域
本发明涉及一种治疗有此治疗需求的雌性宿主中不孕症的方法,包含给雌性宿主施用对卵巢卵泡刺激有效量的依美西坦(exemestane)。
发明背景
依据Harrison字典,人类不孕症被定义为在非保护性性交12个月后不具备受孕的能力。从减少的受孕几率或医疗介入的需要到导致不孕症的不可逆因素,存在一系列的不孕症。不孕症主要归因于配偶中男性因素的有25%,女性因素有58%,约17%的原因不明。
排卵是一个卵子(ovum)或卵蛋白(ova)从卵巢中释放的过程。月经周期内的排卵时期对受精来说是最重要的。公知的是卵泡在受到垂体促性腺激素刺激生长和成熟之后获得了排卵能力。诱导排卵是通常对不孕症患者采用的一种治疗过程。尤其为了以下两种目的应采取诱导排卵:1)治疗患有低促性腺素功能减退症(hypogonadotropic hypogonadism)、多囊性卵巢综合征(polycystic ovary syndrome)和其他月经周期紊乱的患者中的不排卵,和2)刺激准备接受辅助生殖技术的患者(大部分具有正常的月经周期)中的多重卵泡的发生(multiple folliculogenesis)。这些方法也被称之为受控卵巢刺激或过度刺激。然而存在几种由诱导排卵引起的并发症,包括例如多胎妊娠和卵巢过度刺激综合症。这些并发症大部分发生在多囊性卵巢综合征患者和/或应用足量促性腺素疗法中。
本发明的发明人已经发现依西美坦能够被安全地应用于卵巢卵泡刺激,以治疗有此治疗需求的宿主中的不孕症,即不产生上述副作用。
US专利4,808,616中首先教导了依西美坦,其目前在治疗绝经后妇女的乳腺癌中以25mg/天的剂量口服给药。依西美坦被赋予了一种芳香酶抑制的特殊机理。该芳香酶(450arom)是细胞色素P450血红素蛋白的一种特殊形式,由P450(亚铁血红素)部分和肽部分组成。这种酶催化导致雄激素底物(主要是雄甾烯二酮)的A环转为雌激素酮的芳香化的多级反应,这需要存在辅助因子NADPH。在酶反应之后,该酶分子再次得到以进行一次新的芳香化。现已对依西美坦的芳香酶抑制机理做了广泛研究,并已发现该化合物导致了酶失活。事实上,依西美坦在结构上与天然底物雄甾烯二酮相关,最初被认为是芳香酶的假底物,因此它与雄甾烯二酮竞争该酶的活性位点。该化合物随即被转化为(通过NADPH依赖性机理)中间物,该中间物与酶不可逆结合导致其失活(也称之为自杀抵制)。因此酶无疑已被灭活,新生酶的合成需要雌激素的产生。
事实上,新发现的依西美坦的治疗用途确实令人惊讶。从药理学观点看,在几种共存因素中可以发现依西美坦对卵巢卵泡刺激的活性,包括它特殊的芳香酶失活机理,剂量及其治疗方案。
发明内容
本发明的第一个目的是提供一种治疗有此治疗需求的雌性宿主中不孕症的方法,包含给所述宿主施用对治疗上刺激卵泡有效量的依美西坦。
根据本发明的一个优选的实施方案,提供一种在有此治疗需求的雌性宿主中诱导卵巢卵泡刺激的方法,包含对所述的宿主施用随后消除的治疗上卵泡刺激有效量和/或抑制量的依美西坦。
根据本发明,雌性宿主是,例如雌性哺乳动物,尤其是女人。这种宿主的优选实例为患有低促性腺素功能减退症、多囊性卵巢综合征和其他月经周期紊乱的患者,要不然则为准备接受辅助生殖技术的患者。
此处所用的临床术语具有它们在本领域公知的全部意义。
无论如何,不排卵当然指的是缺乏排卵。卵巢卵泡刺激是指用依西美坦引起否则不排卵的雌性宿主排卵,结果产生诱导卵泡破裂和可受精卵母细胞排卵的过程。
此处使用的术语“治疗上刺激卵泡有效量”指的是在治疗不孕症中,对患者单剂量或多剂量施用的有效量,例如当被服用时或在其停用后通过诱导卵巢卵泡刺激引起卵巢的再次过度刺激(rebound hyperstimulation)。
根据本发明的一个进一步优选的实施方案,提供了一种用于患有低促性腺素功能减退症、多囊性卵巢综合征的雌性宿主中和其他月经周期紊乱者,或准备接受辅助生殖技术的候选人的诱导卵巢卵泡刺激的方法,其包含对所述的患者施用治疗上刺激卵泡有效量的依美西坦。
本发明另一个目的是依美西坦在制备用于治疗雌性宿主不孕症的药物中的应用。
本发明还提供了依美西坦在制备用于诱导雌性宿主卵巢卵泡刺激的药物中的应用。
依西美坦在刺激卵巢卵泡上的作用可以在例如动物模型中看到,一旦停止给药即可导致卵泡发育和破裂的增加。
依据本发明的有效治疗,依西美坦可以按照任何在治疗有效量时使该化合物生物上可利用的形式或模式给药。例如,给药途径包括口服给药,舌下给药,鼻内给药,皮下给药,皮内给药,腹膜给药,肌内给药,静脉给药,经皮给药,阴道给药,直肠给药和相似途径等。通常优选口服或肌内给药。制剂领域的技术人员可根据个体情况容易地选择适当的给药形式和模式。例如,适当的口服形式的例子有片剂,胶囊,糖包衣和薄膜包衣片剂。当然,使用的依西美坦的剂量取决于多种因素,例如治疗对象(例如年龄,体重和健康的一般状况)和治疗方案。
依西美坦可例如以约5mg/天-约200mg/天的剂量,以分剂量例如从2至3或4的形式口服施用于女人。
根据一个优选的治疗方案,在月经周期的早期(第5天-第7天)施用依西美坦,然后停止,或在整个周期内给药然后中断,以达到预期的有效的血液卵泡刺激激素水平。
Claims (13)
1.一种治疗有此需求的雌性宿主不孕症的方法,其包含对所述的宿主施用治疗上刺激卵泡有效量的依西美坦。
2.一种诱导有此需求的雌性宿主卵巢卵泡刺激的方法,其包含对所述宿主施用治疗上刺激卵泡有效量的依西美坦。
3.权利要求1或2中所述的方法,其中雌性宿主是雌性哺乳动物。
4.权利要求1或2中所述的方法,其中雌性宿主是女人。
5.权利要求1或2中所述的方法,其中雌性宿主患有低促性腺素功能减退症。
6.权利要求1或2中所述的方法,其中雌性宿主患有多囊性卵巢综合征。
7.权利要求1或2中所述的方法,其中雌性宿主是接受辅助生殖技术的候选人。
8.权利要求1或2中所述的方法,其中依西美坦按照约5mg/天-约200mg/天的剂量给药。
9.权利要求8中所述的方法,其中依西美坦以分剂量形式给药。
10.权利要求1或2中所述的方法,其中依西美坦在月经周期早期给药,然后停止。
11.权利要求1或2中所述的方法,其中依西美坦在整个周期中给药,然后中断。
12.依西美坦在制备用于治疗雌性宿主不孕症的药物中的应用。
13.依西美坦在制备用于诱导雌性宿主卵巢卵泡刺激的药物中的应用。
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US39332002P | 2002-07-02 | 2002-07-02 | |
US60/393,320 | 2002-07-02 |
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CN1665516A true CN1665516A (zh) | 2005-09-07 |
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CN038157306A Pending CN1665516A (zh) | 2002-07-02 | 2003-07-02 | 使用依西美坦治疗不孕症 |
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EP (1) | EP1531829A2 (zh) |
JP (1) | JP2005536490A (zh) |
KR (1) | KR20050077045A (zh) |
CN (1) | CN1665516A (zh) |
AU (1) | AU2003247404A1 (zh) |
BR (1) | BR0312393A (zh) |
CA (1) | CA2491372A1 (zh) |
IL (1) | IL165813A0 (zh) |
MX (1) | MXPA05000251A (zh) |
PL (1) | PL373219A1 (zh) |
WO (1) | WO2004004634A2 (zh) |
ZA (1) | ZA200410135B (zh) |
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KR102432156B1 (ko) * | 2020-05-18 | 2022-08-11 | 제주대학교 산학협력단 | 화학물질을 포함하는 어류의 성 성숙 제어용 조성물 및 이를 이용한 어류의 성 성숙 제어방법 |
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PT1383578E (pt) * | 2001-04-17 | 2008-10-08 | Ares Trading Sa | Inibidor da aromatase em dose única para tratamento da infertilidade |
NZ528501A (en) * | 2001-04-17 | 2008-04-30 | Ares Trading Sa | Aromatase inhibition to enhance assisted reproduction |
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- 2003-07-02 CN CN038157306A patent/CN1665516A/zh active Pending
- 2003-07-02 JP JP2004519563A patent/JP2005536490A/ja active Pending
- 2003-07-02 KR KR1020057000051A patent/KR20050077045A/ko not_active Application Discontinuation
- 2003-07-02 WO PCT/US2003/016252 patent/WO2004004634A2/en active Application Filing
- 2003-07-02 PL PL03373219A patent/PL373219A1/xx not_active Application Discontinuation
- 2003-07-02 EP EP03762980A patent/EP1531829A2/en not_active Withdrawn
- 2003-07-02 AU AU2003247404A patent/AU2003247404A1/en not_active Abandoned
- 2003-07-02 MX MXPA05000251A patent/MXPA05000251A/es unknown
- 2003-07-02 BR BR0312393-6A patent/BR0312393A/pt not_active IP Right Cessation
- 2003-07-02 CA CA002491372A patent/CA2491372A1/en not_active Abandoned
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2004
- 2004-12-16 IL IL16581304A patent/IL165813A0/xx unknown
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- 2005-12-15 ZA ZA200410135A patent/ZA200410135B/en unknown
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Publication number | Publication date |
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AU2003247404A1 (en) | 2004-01-23 |
EP1531829A2 (en) | 2005-05-25 |
JP2005536490A (ja) | 2005-12-02 |
WO2004004634A2 (en) | 2004-01-15 |
KR20050077045A (ko) | 2005-07-29 |
IL165813A0 (en) | 2006-01-15 |
ZA200410135B (en) | 2006-07-26 |
BR0312393A (pt) | 2005-04-12 |
CA2491372A1 (en) | 2004-01-15 |
PL373219A1 (en) | 2005-08-22 |
MXPA05000251A (es) | 2005-07-15 |
WO2004004634A3 (en) | 2004-04-08 |
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