CN1674907A - 瑞波西汀在治疗热潮红中的用途 - Google Patents
瑞波西汀在治疗热潮红中的用途 Download PDFInfo
- Publication number
- CN1674907A CN1674907A CNA038188341A CN03818834A CN1674907A CN 1674907 A CN1674907 A CN 1674907A CN A038188341 A CNA038188341 A CN A038188341A CN 03818834 A CN03818834 A CN 03818834A CN 1674907 A CN1674907 A CN 1674907A
- Authority
- CN
- China
- Prior art keywords
- patient
- reboxetine
- hot flush
- treatment
- day
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Reproductive Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Toxicology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
本申请描述了在受其困扰的患者中治疗或预防热潮红的方法,该方法包括对所述患者施用治疗有效剂量的选自瑞波西汀、S,S-瑞波西汀或其可药用盐的化合物。
Description
发明领域
本发明描述了热潮红(hot flashes)的新疗法。该疗法包括对需要其的患者施用药物瑞波西汀、其可药用盐、其衍生物或其前体药物。
发明背景
热潮红是一种常见病。患者出现突然发热,所述发热通常从面部开始,然后可发展到颈部、胸部和身体的其余部位。通常该发作伴有皮肤潮红和/或大量出汗。这些发作每天可出现数次,使经历它们的人非常不适。
尽管不知道引起热潮红的确切原因,但它们通常被归因于患者的激素系统失衡。一大类经历热潮红的患者是绝经期女性。迄今为止,这类患者经常接受雌激素或激素替代治疗来缓解或预防包括热潮红在内的绝经期症状(B.Daly等人,Br.Med.J.1993;307:836-840)。然而,一些女性不愿意接受激素治疗。已经倡导使用一系列基于草药的“天然”治疗包括黑升麻、植物雌激素、亚麻籽、红三叶草、维生素E(D.L.Barton等人,J.Clin.Oncol.1998,16:495-500)、人参和月见草油作为可能的药物治疗(Wisconsin大学医学院,网络课程,“用于绝经期症状的可供选择的方法:证据综述”;www.cme.wisc.edu/online/menopause)。然而,这些疗法并非全部有效(K.I.Pritchard,The Oncologist,2001,6(4),353-362)。
已经被建议使用的其它药物治疗有选择性5-羟色胺重摄取抑制剂(SSRI)如盐酸氟西汀(Prozac;C.Loprinzi;
www.medicine-news.com/ articles/pharma/misc/hotflashes.html)和盐酸帕罗西汀(Paxil;V.Stearns等人,Ann.Oncol.,2000,11:17-22)以及盐酸文拉法辛(Effexor,C.L.Loprinzi等人,J.Clin.Oncol.,1998,16:2377-2381),其是5-羟色胺和去甲肾上腺素重摄取抑制剂。
还已证明低剂量的醋酸甲地孕酮可降低男性和女性中热潮红的频率(Loprinzi等人,N.Engl.J.Med.1994,331:347-351)。其可能的副作用是慢性肾上腺功能不全和体重增加。透皮可乐定也已被用于降低热潮红的频率和严重程度(R.M.Goldberg等人,J.Clin.Onc.1994,12:155-158;R.M.Goldberg等人,J.Clin.Oncol.1994,12:155-158;L.R.Laufer,Obstet.Gynecol.1982,60:583-586)。然而,在一些患者中观察到有副作用如困倦、疲劳和低血压症状。
作为癌症治疗的副作用,男性和女性均可患有热潮红。某些药物如用于治疗乳腺癌的他莫昔芬(枸橼酸他莫昔芬)以及用于治疗前列腺癌的亮丙瑞林(醋酸亮丙瑞林)和醋酸性瑞林(性瑞林)均可导致热觉。针对前列腺癌或睾丸癌的双侧睾丸切除术也影响激素系统以至于患者可继发热潮红。尤其是对于癌症患者,通常不建议使用激素替代治疗,因为顾忌到会刺激癌症再生长。
由于现有技术的缺点,仍然需要能降低热潮红的次数和/或严重程度的其它药物治疗。现已发现瑞波西汀可有效治疗这些发作。
发明简述
本发明提供了在受其困扰的患者中治疗和/或预防热潮红的方法,该方法包括对所述患者施用治疗有效剂量的选自瑞波西汀、其可药用盐、其衍生物或其前体药物的化合物。
在另一个实施方案中,公开了选自瑞波西汀、其可药用盐、其衍生物或其前体药物的化合物在制备治疗和/或预防热潮红的药物中的用途。
本发明还涉及在受其困扰的患者中治疗和/或预防激素变化的症状的方法,该方法包括对所述患者施用治疗有效剂量的选自瑞波西汀、其对映体或非对映体、其可药用盐、其衍生物或其前体药物的化合物。
发明详述
瑞波西汀是化学名为2-[α-(2-乙氧基)苯氧基苄基]吗啉的药用物质及其可药用盐的通用名。瑞波西汀还以商标名VESTRA、EDRONAX、PROLIFT、INTEGREX和NOREBOX被公知。除了R,R-和S,S-对映体的外消旋混合物外,还可优选将纯S,S-对映体用于本发明。
瑞波西汀被用作抗抑郁药。抗抑郁药通常划分为类或“代”。第一代抗抑郁药通常是三环类抗抑郁药如影响多种神经递质系统并与多种不希望的副作用有关的马普替林。第二代抗抑郁药如米安舍林、米氮平和曲唑酮基本没有抗胆碱能作用,并且它们的抗肾上腺素作用和抗组胺作用更弱。这些与仅介导造成抑郁的三种主要神经递质系统(5-HT、去甲肾上腺素、多巴胺)之一的第三代抗抑郁药(例如SSRI、依沙匹隆、维洛沙嗪、瑞波西汀、丁氨苯丙酮)不同,它们不影响毒蕈碱、组胺和肾上腺素能脑系统。J.Svestka.“第三、四和五代抗抑郁药”,Cesk-Psychiatr.1994年2月;90(1):3-19(捷克语)。
然而瑞波西汀与大多数抗抑郁药的作用方式不同。与三环类抗抑郁药和甚至是选择性5-羟色胺重摄取抑制剂(SSRI)不同,瑞波西汀在8-OH-DPAT低温试验中无效,这表明瑞波西汀不是选择性5-羟色胺重摄取抑制剂,而是对去甲肾上腺素能系统有选择性。因此,瑞波西汀不是SSRI,而被认为是一种新的选择性去甲肾上腺素重摄取抑制剂(NARI)。B.E.Leonard,“抑郁基础模型中的去甲肾上腺素”。European-Neuropsychopharmacol.1997年4月;7增刊1:S11-6;讨论S71-3。与大多数药物不同,瑞波西汀是一种高度选择性的去甲肾上腺素重摄取抑制剂,仅有微弱的5-羟色胺重摄取抑制活性且没有多巴胺重摄取抑制活性。该化合物在不同的动物模型中仅表现出弱的抗胆碱能活性或无抗胆碱能活性,并且没有单胺氧化酶(MAO)抑制活性。
瑞波西汀高度有效且迅速起效。我们的研究表明瑞波西汀具有有效的抗利血平活性,并且还具有经典三环类抗抑郁药对去甲肾上腺素重摄取的抑制性质,能使J-肾上腺素能受体功能脱敏而不表现出任何明显的与毒蕈碱胆碱能和I-肾上腺素能受体的相互作用。此外,瑞波西汀还表现出较其它三环类抗抑郁药更低的消除迷走神经作用的活性。
发明人已发现:由于其独特的性质,瑞波西汀特别可用于治疗或预防热潮红。另外,发明人还已发现瑞波西汀可用于治疗或预防患者的激素改变的症状。
在本发明中,瑞波西汀可以以其游离碱形式使用。另外,还可以使用瑞波西汀甲磺酸盐(也称为甲磺酸瑞波西汀)或任何其它不显著影响该物质药学活性的可药用盐如其琥珀酸盐或富马酸盐。使用瑞波西汀的可药用衍生物和可药用的前体药物也是可能的。表述“前体药物”是指已知的直接起作用的药物的衍生物,与该药物相比,该衍生物具有改进的递送特性和治疗价值,并且可通过酶促过程、例如通过在血液中的水解作用或化学过程被转化为活性药物[参见H.Bundgaard,“前体药物设计:各种官能团和化学个体的生物可逆的衍生物”,Design of Prodrugs(H.Bundgaard编辑),Elsevier,N.Y.(1985)]。
瑞波西汀和其各种衍生物以及它们的合成方法在U.S.4,229,449(Melloni等人)中有描述,在此将其引入作为参考。制备瑞波西汀的方法在US 5,068,433(Melloni等人)和US 5,391,735(Melloni等人)中也有描述,将两者均引入作为参考。
瑞波西汀可通过减少发作的次数和/或严重程度而用于治疗或预防热潮红。本发明所治疗的热潮红可由多种原因引起。瑞波西汀可用于治疗或预防作为绝经后期的症状出现的热潮红,而且如果热潮红有其它起因,瑞波西汀也是有效的。特别是各种医学治疗可使女性和男性患者的激素系统失衡,从而导致热潮红发作。
具有低水平雌激素的女性患者易于患有热潮红。这种缺乏可由能过早地导致绝经的放射治疗引起,或者可由特定的药物治疗如抗雌激素治疗或某些药物(例如他莫昔芬(枸橼酸他莫昔芬))引起。
雄激素丧失是男性热潮红的一种原因。激素系统失衡也可以由药物(例如亮丙瑞林(醋酸亮丙瑞林)和醋酸性瑞林(性瑞林))诱发或由放射诱发。手术如针对前列腺癌或睾丸癌的双侧睾丸切除术是另一种可能的原因。
瑞波西汀可以以药物组合物形式施用于患者。可用于本发明的药物组合物和施用方法例如在US 4,229,449第18栏第33-66行中有描述。在此将该文献特别引入作为参考。可药用的载体和赋形剂以及其它辅剂是本领域中已知的,并且可根据预期的施用途径进行选择。
瑞波西汀可以以约1至超过20mg/kg活性成分的剂量施用。更通常的是以每名患者每天1至20mg的剂量提供。该化合物可以以包括常规口服剂型在内的任何适宜的方法施用。优选的方法是每天两次口服给药。优选的剂量范围为每名患者每天4至10mg,最优选的剂量为每名患者每天6至8mg或8至10mg,这根据患者而定,每天两次(b.i.d.)进行递送。还可以以每名患者每天2、4、6、8、10或12mg的剂量或其部分进行给药。例如,适宜的施用可以是早上4mg和晚上2或4mg,或者早上6mg和晚上4mg。在一些患者中,理想的剂量是早上3-5mg和晚上3-5mg。熟练的执业人员可确定精确的剂量水平。理想的剂量可通过临床试验评价和患者的需要来常规确定。
瑞波西汀可有效治疗热潮红。其特别可用于治疗正在形成或已经患有癌症、因此不应当接受激素替代治疗的患者。本发明现在提供了一种治疗这些不希望的发作的新的且安全的方法。
Claims (22)
1.在需要其的患者中治疗或预防热潮红的方法,该方法包括对所述患者施用治疗有效剂量的选自瑞波西汀或S,S-瑞波西汀、其可药用盐、其衍生物或其前体药物的化合物。
2.权利要求1的方法,其中患者为女性。
3.权利要求2的方法,其中热潮红为绝经期或绝经后期的症状。
4.权利要求2的方法,其中热潮红由医学治疗引起。
5.权利要求2的方法,其中热潮红由放射治疗引起。
6.权利要求2的方法,其中热潮红由药物诱发。
7.权利要求2的方法,其中患者正在接受抗雌激素治疗。
8.权利要求2的方法,其中患者正在形成或已经患有癌症。
9.权利要求5的方法,其中癌症为乳腺癌。
10.权利要求1的方法,其中患者为男性。
11.权利要求10的方法,其中热潮红由放射治疗引起。
12.权利要求10的方法,其中热潮红由药物诱发。
13.权利要求10的方法,其中患者有雄激素丧失。
14.权利要求10的方法,其中患者正在形成或已经患有癌症。
15.权利要求14的方法,其中癌症为前列腺癌或睾丸癌。
16.权利要求1的方法,其中瑞波西汀的剂量范围为每名患者每天4至10mg。
17.权利要求1的方法,其中瑞波西汀的剂量范围为每名患者每天6至8mg。
18.权利要求1的方法,其中化合物以还包含可药用载体或赋形剂的药物组合物形式施用。
19.选自瑞波西汀或S,S-瑞波西汀或其可药用盐、其衍生物或其前体药物的化合物在制备治疗或预防热潮红的药物中的用途。
20.权利要求19的用途,其中瑞波西汀的剂量范围为每名患者每天4至10mg。
21.权利要求19的用途,其中瑞波西汀的剂量范围为每名患者每天6至8mg。
22.在受其困扰的患者中治疗或预防激素改变的症状的方法,该方法包括对所述患者施用治疗有效剂量的选自瑞波西汀、其可药用盐、其衍生物或其前体药物的化合物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US40354902P | 2002-08-14 | 2002-08-14 | |
US60/403,549 | 2002-08-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1674907A true CN1674907A (zh) | 2005-09-28 |
Family
ID=31888245
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA038188341A Pending CN1674907A (zh) | 2002-08-14 | 2003-08-04 | 瑞波西汀在治疗热潮红中的用途 |
Country Status (14)
Country | Link |
---|---|
US (1) | US20040092519A1 (zh) |
EP (1) | EP1530476A1 (zh) |
JP (1) | JP2005537307A (zh) |
KR (1) | KR20050049476A (zh) |
CN (1) | CN1674907A (zh) |
AU (1) | AU2003261185A1 (zh) |
BR (1) | BR0313411A (zh) |
CA (1) | CA2495452A1 (zh) |
IL (1) | IL166266A0 (zh) |
MX (1) | MXPA05001705A (zh) |
NZ (1) | NZ537521A (zh) |
PL (1) | PL373956A1 (zh) |
WO (1) | WO2004016272A1 (zh) |
ZA (1) | ZA200500152B (zh) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050080143A1 (en) * | 2001-11-29 | 2005-04-14 | Steiner Mitchell S. | Treatment of androgen-deprivation induced osteoporosis |
US7365076B2 (en) | 2003-10-14 | 2008-04-29 | Wyeth | Substituted aryl cycloalkanol derivatives and methods of their use |
US7491723B2 (en) | 2003-10-14 | 2009-02-17 | Wyeth | Alkanol and cycloalkanol-amine derivatives and methods of their use |
US7550485B2 (en) | 2003-10-14 | 2009-06-23 | Wyeth | Substituted N-heterocycle derivatives and methods of their use |
US7402698B2 (en) | 2003-10-14 | 2008-07-22 | Wyeth | Secondary amino-and cycloamino-cycloalkanol derivatives and methods of their use |
US7524846B2 (en) | 2003-10-14 | 2009-04-28 | Wyeth | Arylalkyl- and cycloalkylalkyl-piperazine derivatives and methods of their use |
US7419980B2 (en) | 2003-10-14 | 2008-09-02 | Wyeth | Fused-aryl and heteroaryl derivatives and methods of their use |
US7531543B2 (en) | 2003-10-14 | 2009-05-12 | Wyeth | Phenylpiperazine cycloalkanol derivatives and methods of their use |
US7517899B2 (en) | 2004-03-30 | 2009-04-14 | Wyeth | Phenylaminopropanol derivatives and methods of their use |
US7414052B2 (en) | 2004-03-30 | 2008-08-19 | Wyeth | Phenylaminopropanol derivatives and methods of their use |
US20080033050A1 (en) | 2006-08-04 | 2008-02-07 | Richards Patricia Allison Tewe | Method of treating thermoregulatory disfunction with paroxetine |
US20100069389A1 (en) * | 2008-09-06 | 2010-03-18 | Bionevia Pharmaceuticals, Inc. | Novel forms of reboxetine |
WO2013185024A1 (en) | 2012-06-08 | 2013-12-12 | The Ohio State University | Treating burn and scar injury using tocotrienol |
CA2980990A1 (en) * | 2015-04-07 | 2016-10-13 | Meiji Co., Ltd. | Hot flash-suppressing agent |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL56369A (en) * | 1978-01-20 | 1984-05-31 | Erba Farmitalia | Alpha-phenoxybenzyl propanolamine derivatives,their preparation and pharmaceutical compositions comprising them |
GB8419683D0 (en) * | 1984-08-02 | 1984-09-05 | Erba Farmitalia | 3-substituted derivatives of 1-amino-2-hydroxy-propane |
US5464854A (en) * | 1993-11-11 | 1995-11-07 | Depadova; Anathony S. | Method of modifying ovarian hormone-regulated AT1 receptor activity as treatment of incapacitating symptom(s) of P.M.S. |
EA011094B1 (ru) * | 1999-07-01 | 2008-12-30 | Фармация Энд Апджон Компани | Высокоселективные ингибиторы обратного захвата норэпинефрина и способы их применения |
ES2287021T3 (es) * | 1999-07-22 | 2007-12-16 | University Of Rochester | Metodo para el tratamiento de sintomas de variacines hormonales que incluyen el fogaje. |
AU6634000A (en) * | 1999-08-13 | 2001-03-13 | Vela Pharmaceuticals Inc. | Cyclobenzaprine for treating generalized anxiety disorder and compositions thereof |
SK5422003A3 (en) * | 2000-11-15 | 2003-12-02 | Lilly Co Eli | Treatment of anxiety disorders |
WO2002078691A1 (en) * | 2001-03-29 | 2002-10-10 | Eli Lilly And Company | Duloxetine for treatment of hot flashes |
DE10130020A1 (de) * | 2001-06-25 | 2003-12-04 | Gruenenthal Gmbh | Substituierte 1-Oxa-2,8-diaza-spiro[4.5]dec-2-en-derivate |
US6635675B2 (en) * | 2001-11-05 | 2003-10-21 | Cypress Bioscience, Inc. | Method of treating chronic fatigue syndrome |
AU2002352625A1 (en) * | 2001-12-11 | 2003-06-23 | Eli Lilly And Company | Use of norepinephrine reuptake inhibitors for the treatment of cognitive failure |
-
2003
- 2003-08-04 NZ NZ537521A patent/NZ537521A/en unknown
- 2003-08-04 WO PCT/US2003/022491 patent/WO2004016272A1/en not_active Application Discontinuation
- 2003-08-04 AU AU2003261185A patent/AU2003261185A1/en not_active Abandoned
- 2003-08-04 US US10/633,762 patent/US20040092519A1/en not_active Abandoned
- 2003-08-04 BR BR0313411-3A patent/BR0313411A/pt not_active IP Right Cessation
- 2003-08-04 CA CA002495452A patent/CA2495452A1/en not_active Abandoned
- 2003-08-04 EP EP03788249A patent/EP1530476A1/en not_active Withdrawn
- 2003-08-04 KR KR1020057002435A patent/KR20050049476A/ko not_active Application Discontinuation
- 2003-08-04 MX MXPA05001705A patent/MXPA05001705A/es unknown
- 2003-08-04 PL PL03373956A patent/PL373956A1/xx not_active Application Discontinuation
- 2003-08-04 CN CNA038188341A patent/CN1674907A/zh active Pending
- 2003-08-04 JP JP2004529097A patent/JP2005537307A/ja active Pending
-
2005
- 2005-01-07 ZA ZA200500152A patent/ZA200500152B/en unknown
- 2005-01-12 IL IL16626605A patent/IL166266A0/xx unknown
Also Published As
Publication number | Publication date |
---|---|
MXPA05001705A (es) | 2005-04-19 |
PL373956A1 (en) | 2005-09-19 |
ZA200500152B (en) | 2006-07-26 |
NZ537521A (en) | 2007-05-31 |
IL166266A0 (en) | 2006-01-15 |
EP1530476A1 (en) | 2005-05-18 |
CA2495452A1 (en) | 2004-02-26 |
WO2004016272A1 (en) | 2004-02-26 |
KR20050049476A (ko) | 2005-05-25 |
BR0313411A (pt) | 2005-06-28 |
JP2005537307A (ja) | 2005-12-08 |
US20040092519A1 (en) | 2004-05-13 |
AU2003261185A1 (en) | 2004-03-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI330083B (en) | Methods for treating or preventing symptoms of hormonal variations | |
ZA200500152B (en) | Use of reboxetine for the treatment of hot flashes | |
JP2003520817A (ja) | エストロゲンと組み合わせた選択的エストロゲン受容体モジュレータ | |
EA003142B1 (ru) | Лекарственное средство, обладающее антидепрессивным действием, его применение и способ лечения | |
JPS59193821A (ja) | 抗不安薬としてのフルオキセチンの使用法 | |
WO1997025037A1 (en) | Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of prostatic carcinoma | |
US6835728B2 (en) | Drug combination for the treatment of depression and related disorders comprising mirtazapine | |
CN103520725B (zh) | 一种治疗呕吐的药物组合物 | |
CN1142767A (zh) | 2,3-二芳基-1-苯丙吡喃衍生物在生产治疗和预防骨损失和骨质疏松症药物中的用途 | |
JP2004525940A (ja) | 火照りの処置のためのデュロキセチン | |
RU2560840C2 (ru) | Способ лечения бессонницы | |
TW200307553A (en) | Treatment of post-menopausal complaints in breast cancer patients | |
EP0873119A1 (en) | Use of the l-enantiomer of centchroman for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of breast cancer | |
MXPA02008659A (es) | Tratamiento de la psoriasis. | |
KR20140098865A (ko) | 파록세틴으로 체온 조절 기능 이상을 치료하는 방법 | |
US5780502A (en) | Use of 3,4-diphenyl chromans for the manufacture of a pharmaceutical composition for inhibiting one or more symptoms of premenstrual syndrome | |
JP2008513430A (ja) | 月経前症候群および月経前不快気分障害の処置のためのピンドロール | |
CZ20023025A3 (cs) | Léčba chorob vztahujících se k serotonergnímu systému | |
EP1345599A1 (en) | Treatment of obsessive compulsive disorder | |
SK3272001A3 (en) | A new composition | |
JP2000514441A (ja) | 月経前症候群の1又は複数の症状を抑制するための医薬組成物の製造のための3,4―ジフェニルクロマンの使用 | |
Sood et al. | Allopathic and complementary alternatives to hormone replacement therapy | |
Sutton et al. | Pharmacological Interventions: Addressing Residuals and Outcomes | |
Al-Doghether | An overview of pharmacological aids available to enhance smoking cessation. | |
CN108883083A (zh) | 两种氯米芬异构体的口服剂型及使用其治疗继发性腺功能减退症的方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1078778 Country of ref document: HK |
|
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: 1078778 Country of ref document: HK |