CN101049290B - 阿戈美拉汀在制备用于治疗广泛性焦虑症的药物中的用途 - Google Patents
阿戈美拉汀在制备用于治疗广泛性焦虑症的药物中的用途 Download PDFInfo
- Publication number
- CN101049290B CN101049290B CN2007100910721A CN200710091072A CN101049290B CN 101049290 B CN101049290 B CN 101049290B CN 2007100910721 A CN2007100910721 A CN 2007100910721A CN 200710091072 A CN200710091072 A CN 200710091072A CN 101049290 B CN101049290 B CN 101049290B
- Authority
- CN
- China
- Prior art keywords
- agomelatine
- anxiety disorder
- generalized anxiety
- application
- treating
- 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.)
- Active
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
- A61K31/04—Nitro compounds
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及阿戈美拉汀或N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺在制备用于治疗广泛性焦虑症的药物中的用途。
Description
技术领域
本发明涉及式(I)的阿戈美拉汀或N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺和其水合物、晶体形式和可药用酸或碱的加成盐在制备用于治疗广泛性焦虑症或GAD的药物中的用途,
背景技术:
阿戈美拉汀,或N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺,具有双重特性,一方面它是褪黑激素能系统受体激动剂,另一方面它是5-HT2C受体拮抗剂。这些性质使得它在中枢神经系统中具有活性,尤其是在重症抑郁、季节性情感障碍、睡眠障碍、心血管疾病、消化系统疾病、由时差导致的失眠和疲劳、食欲障碍和肥胖症的治疗中有活性。
欧洲专利说明书EP 0447285和EP 1564202中已经描述了阿戈美拉汀、其制备方法和在治疗中的用途。
发明内容:
本申请人现已发现阿戈美拉汀或N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺和其水合物、晶体形式和可药用酸或碱的加成盐具有有价值的性质,该性质使其可用于治疗广泛性焦虑症。
广泛性焦虑症符合充分定义的标准并构成一完全的病情实体(300.02-DSM IV-Mental Troubles Diagnostic and Statistic handbook,第4版,American Psychiatric Association),其特征在于深度的和没有理由的焦虑。这种慢性疾病导致了众多相关的问题,特别是认知功能障碍,更特别地涉及思想和精神的表现、在思维和判断上的改变并因而造成行为的改变,并且还导致了精神性运动的问题,这是反应笨拙、反应能力低下或甚至于没有反应能力的根源(Wittchen HU等人,Arch Gen Psychiatry,1994,51(5),355-364)。
美国和欧洲的卫生当局已经意识到了该病症的独特性,他们颁布了特别针对该适应症的药物的开发的指导原则(Committee for ProprietaryMedicinal Products(CPMP)/EWP/4284/02/伦敦-2005年1月20日-用于治疗广泛性焦虑症的医药产品的临床研究指导原则)。
近来的流行病学研究表明该疾病的全球人口发病率为5%至6%,在大于40岁的妇女中的发病率高至10%。所以从健康和经济两个方面来看该病症的影响是重大的。
最近,推荐施用例如万拉法新、帕罗西汀或西酞普兰(escitalopram)。但是对于这些不同的治疗已经列出了大量的副反应,被报道的频率最高的副反应为镇静、药物依赖、酒精相互作用和不可忽略的对心血管和/或性方面的影响等。除此之外,在大多数情况下,治疗的停止可导致停药综合征,这对患者来说是不能接受的。
所以,正如在CPMP指导原则中所强调的那样,努力开发对于这种疾病的新的治疗是必要的。
具有新的药理学性质的新化学实体阿戈美拉汀在重症抑郁症中在对照的临床研究中与安慰剂相比显示了高的有效性。本申请人现已发现由于它的药理学性质阿戈美拉汀可用于广泛性焦虑症中。
在患有广泛性焦虑症的患者中进行的与安慰剂对照的临床研究充分表明了阿戈美拉汀真正适合于该障碍的治疗。
此外,除了观察到的在治疗广泛性焦虑症中的有效性外,对于患者而言阿戈美拉汀也具有良好的可接受性:特别地,阿戈美拉汀没有通常与精神药物有关的副作用。在这些副作用中,典型精神药物停止治疗时观察到的停药综合征,用阿戈美拉汀时没有观察到,这使得其在该疾病中成为治疗选择。
因此,本发明也涉及阿戈美拉汀和其水合物、晶体形式和可药用酸或碱的加成盐在制备用于治疗广泛性焦虑症的药物组合物中的用途。
特别地,本发明涉及如专利说明书EP 1564202所述的以晶体II形式获得的阿戈美拉汀在制备用于治疗广泛性焦虑症的药物组合物中的用途。
药物组合物将以适于经口服、胃肠道外、经皮、经鼻、直肠或经舌途径施用的形式存在,特别是以可注射的制剂、片剂、舌下片、glossettes、明胶胶囊、胶囊、锭剂、栓剂、乳膏剂、软膏剂、皮肤凝胶等等。
除了阿戈美拉汀和任选与其组合的情绪稳定剂之外,本发明的药物组合物还包含一种或多种选自稀释剂、润滑剂、粘合剂、崩解剂、吸收剂、着色剂、甜味剂等等的赋形剂或载体。
可被提及的非限制性的实例有:
◆稀释剂:乳糖、葡萄糖、蔗糖、甘露醇、山梨醇、纤维素、甘油,
◆润滑剂:二氧化硅、滑石粉、硬脂酸及其镁盐和钙盐、聚乙二醇,
◆粘合剂:硅酸镁铝、淀粉、明胶、西黄蓍胶、甲基纤维素、羧甲基纤维素钠和聚乙烯吡咯烷酮,
◆崩解剂:琼脂、海藻酸及其钠盐、泡腾混合物。
可用的剂量根据患者的性别、年龄及体重、施用途径、障碍的性质以及任何有关的治疗的不同而不同,范围为每24小时1mg至50mg阿戈美拉汀。
阿戈美拉汀的日剂量优选为每天25mg,存在着增加至每天50mg的可能性。
具体实施方式:
药物组合物:
制备1000片片剂的配方,每片包含25mg活性成分:
N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺.....................25g
乳糖一水合物..........................................62g
硬脂酸镁..............................................1.3g
聚维酮................................................9g
无水胶态二氧化硅......................................0.3g
羧甲基纤维素钠........................................30g
硬脂酸................................................2.6g
临床研究:
在121名患者中进行了与安慰剂对照的临床研究。将121名患者随机分入两个平行组,并接受每天25mg的阿戈美拉汀或安慰剂。
在治疗两周后,在低反应的情况下,在用IVRS系统(交互语音响应系统)接受阿戈美拉汀的患者的双盲研究中将剂量增加至每天50mg。进行12周的治疗。
用卫生当局推荐的评价工具例如Hamilton Anxiety Scale(HamiltonM.,J.Neurol.Neurosurg.Psychiat.,1959,23,56-62),或Sheehan DisabilityScale(International Clinical Psychopharmacology,1966,11,89-95)进行有效性的评价。也评价了可接受性。
获得的结果表明,在Hamilton评分表的总得分(评价的第一标准)中,阿戈美拉汀治疗组和安慰剂组之间的差别为-3.28(p=0.040),对应于临床和统计上的显著差别。
本研究也显示了患者的良好可接受性,并且当停止治疗时也不存在停药综合征。
Claims (2)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR06/03083 | 2006-04-07 | ||
FR0603083A FR2899472B1 (fr) | 2006-04-07 | 2006-04-07 | Utilisation de l'agomelatine pour l'obtention de medicaments destines au traitement du trouble anxiete generalisee |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101049290A CN101049290A (zh) | 2007-10-10 |
CN101049290B true CN101049290B (zh) | 2012-10-31 |
Family
ID=37308935
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2007100910721A Active CN101049290B (zh) | 2006-04-07 | 2007-04-06 | 阿戈美拉汀在制备用于治疗广泛性焦虑症的药物中的用途 |
Country Status (44)
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101481321B (zh) * | 2009-02-27 | 2012-04-18 | 上海医药工业研究院 | 阿戈美拉汀卤化氢复合物及其制备方法 |
CN101585779B (zh) * | 2009-03-10 | 2014-04-02 | 上海医药工业研究院 | 阿戈美拉汀的晶型vi及其制备方法和应用 |
FR2956031B1 (fr) * | 2010-02-11 | 2012-03-02 | Servier Lab | Utilisation de l'agomelatine pour l'obtention de medicaments destines au traitement du trouble obsessionnel compulsif (toc) |
CN102190595A (zh) * | 2010-03-17 | 2011-09-21 | 上海医药工业研究院 | 阿戈美拉汀溴化氢水合物及其制备方法 |
CN102190594A (zh) * | 2010-03-17 | 2011-09-21 | 上海医药工业研究院 | 阿戈美拉汀氯化氢水合物及其制备方法 |
PH12012000132A1 (en) * | 2011-06-09 | 2014-10-20 | Servier Lab | New co-crystals of agomelatine, a process for their preparation and pharmaceutical compositions containing them |
FR2978916B1 (fr) * | 2011-08-10 | 2013-07-26 | Servier Lab | Composition pharmaceutique solide pour administration buccale d'agomelatine |
EP2810647A1 (en) | 2013-06-06 | 2014-12-10 | Zentiva, a.s. | Pharmaceutical formulations comprising agomelatine in the form of agomelatine co-crystal with an organic acid |
EP2810656B1 (en) | 2013-06-06 | 2017-08-02 | Zentiva, a.s. | Agomelatine formulations comprising agomelatine in the form of co-crystals |
IT201900002913A1 (it) | 2019-03-01 | 2020-09-01 | Nicola Pescosolido | Composto utile per il trattamento del glaucoma |
CN110867197A (zh) * | 2019-10-23 | 2020-03-06 | 吴杰 | 语音交互过程中实时打断语音机器人的方法及设备 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1680284A (zh) * | 2004-02-13 | 2005-10-12 | 瑟维尔实验室 | 阿戈美拉汀的新合成方法、新晶型及其药物组合物 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2658818B1 (fr) * | 1990-02-27 | 1993-12-31 | Adir Cie | Nouveaux derives a structure naphtalenique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
SG45100A1 (en) * | 1994-03-07 | 1998-01-16 | Ibm | Improvements in image processing |
DE19532842C1 (de) * | 1995-09-05 | 1996-12-19 | Ibm | Bildaufnahmesystem |
AR047553A1 (es) * | 2003-07-04 | 2006-01-25 | Lundbeck & Co As H | La combinacion de un inhibidor de reabsorcion de serotonina y agomelatina |
AU2004308962A1 (en) * | 2003-12-24 | 2005-07-14 | Sepracor Inc. | Melatonin combination therapy for improving sleep quality |
JP2008531714A (ja) * | 2005-03-04 | 2008-08-14 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 不安障害の治療用及び/又は予防用の医薬組成物 |
US7358395B2 (en) * | 2005-08-03 | 2008-04-15 | Les Laboratories Servier | Crystalline form V of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
US7635721B2 (en) * | 2005-08-03 | 2009-12-22 | Les Laboratoires Servier | Crystalline form III of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
TW200735878A (en) * | 2005-11-18 | 2007-10-01 | Astrazeneca Ab | Pharmaceutical compositions |
-
2006
- 2006-04-07 FR FR0603083A patent/FR2899472B1/fr active Active
-
2007
- 2007-03-26 PE PE2007000340A patent/PE20080174A1/es not_active Application Discontinuation
- 2007-03-26 AP AP2007003953A patent/AP2488A/xx active
- 2007-03-28 CR CR9019A patent/CR9019A/es not_active Application Discontinuation
- 2007-03-28 TN TNP2007000118A patent/TNSN07118A1/fr unknown
- 2007-03-28 GT GT200700032A patent/GT200700032A/es unknown
- 2007-03-29 NI NI200700084A patent/NI200700084A/es unknown
- 2007-04-03 MA MA29798A patent/MA28987B1/fr unknown
- 2007-04-03 NO NO20071774A patent/NO20071774L/no not_active Application Discontinuation
- 2007-04-03 CO CO07033655A patent/CO5840252A1/es not_active Application Discontinuation
- 2007-04-04 US US11/732,762 patent/US7960438B2/en active Active
- 2007-04-04 MX MX2007004100A patent/MX2007004100A/es active IP Right Grant
- 2007-04-04 AR ARP070101420A patent/AR060349A1/es unknown
- 2007-04-04 TW TW096112141A patent/TWI374736B/zh active
- 2007-04-05 NZ NZ554347A patent/NZ554347A/en unknown
- 2007-04-05 JO JOP/2007/0119A patent/JO3440B1/ar active
- 2007-04-05 ZA ZA200702865A patent/ZA200702865B/xx unknown
- 2007-04-05 SG SG200702552-1A patent/SG136881A1/en unknown
- 2007-04-05 AU AU2007201527A patent/AU2007201527B2/en active Active
- 2007-04-05 BR BRPI0701601-8A patent/BRPI0701601A/pt not_active Application Discontinuation
- 2007-04-05 GE GEAP20079966A patent/GEP20094743B/en unknown
- 2007-04-05 MY MYPI20070536A patent/MY143269A/en unknown
- 2007-04-06 EP EP07290420A patent/EP1842535B1/fr not_active Revoked
- 2007-04-06 PT PT07290420T patent/PT1842535E/pt unknown
- 2007-04-06 ES ES07290420T patent/ES2351062T3/es active Active
- 2007-04-06 DK DK07290420.4T patent/DK1842535T3/da active
- 2007-04-06 ME MEP-2010-497A patent/ME01865B/me unknown
- 2007-04-06 KR KR1020070034003A patent/KR20070100657A/ko active Search and Examination
- 2007-04-06 WO PCT/FR2007/000586 patent/WO2007116136A1/fr active Application Filing
- 2007-04-06 RS RSP-2010/0497A patent/RS51485B/en unknown
- 2007-04-06 DE DE602007008494T patent/DE602007008494D1/de active Active
- 2007-04-06 JP JP2009503617A patent/JP4880031B2/ja active Active
- 2007-04-06 AT AT07290420T patent/ATE477798T1/de active
- 2007-04-06 EA EA200700574A patent/EA012608B1/ru unknown
- 2007-04-06 PL PL07290420T patent/PL1842535T3/pl unknown
- 2007-04-06 CN CN2007100910721A patent/CN101049290B/zh active Active
- 2007-04-06 SI SI200730345T patent/SI1842535T1/sl unknown
- 2007-04-07 SA SA07280161A patent/SA07280161B1/ar unknown
- 2007-04-09 UY UY30262A patent/UY30262A1/es not_active Application Discontinuation
- 2007-04-10 IL IL182407A patent/IL182407A/en active IP Right Grant
- 2007-04-10 CA CA2584060A patent/CA2584060C/fr active Active
- 2007-12-13 HK HK07113624.0A patent/HK1108367A1/xx unknown
-
2010
- 2010-10-07 CY CY20101100897T patent/CY1111287T1/el unknown
- 2010-10-21 HR HR20100577T patent/HRP20100577T1/hr unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1680284A (zh) * | 2004-02-13 | 2005-10-12 | 瑟维尔实验室 | 阿戈美拉汀的新合成方法、新晶型及其药物组合物 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101049290B (zh) | 阿戈美拉汀在制备用于治疗广泛性焦虑症的药物中的用途 | |
JPS6143112A (ja) | 精神性欲機能障害治療剤 | |
CN1853619B (zh) | 阿戈美拉汀在获得用于治疗双相性精神障碍的药物中的用途 | |
JP5634529B2 (ja) | 強迫性障害(ocd)処置用の薬剤の製造のためのアゴメラチンの使用 | |
CN101194901A (zh) | 阿戈美拉汀在制备用于治疗Smith-Magenis综合征的药物中的用途 | |
US20190224208A1 (en) | Pharmaceutical composition for treating premature ejaculation and method for treating premature ejaculation | |
TW202317101A (zh) | 治療抑鬱狀態之方法 | |
Hirakawa et al. | A case of facial pain in somatic symptom disorder responding to duloxetine | |
US8716347B2 (en) | Tramadol for the treatment of functional gastrointestinal disorders | |
US20110065749A1 (en) | Method and pharmaceutical composition for treatment of mental disorders | |
CN1927205A (zh) | 阿戈美拉汀与去甲肾上腺素重摄取抑制剂的新联合以及包含该联合的药物组合物 | |
JP2009013074A (ja) | 全般性不安障害の処置を目的とする医薬を得るためのアゴメラチンの使用 | |
WO2023086433A1 (en) | Methods and compositions for treating conditions associated with central hypoventilation | |
Milanov et al. | National consensus on the diagnosis and treatment of myasthenia gravis | |
WO2023034265A1 (en) | Methods and compositions for treating sleep apnea | |
WO2021146425A1 (en) | Methods of treating acute muscle spasms | |
US20220071976A1 (en) | Domperidone compositions and methods for treating depression | |
Barthold et al. | Harwood-Nuss' Clinical Practice of Emergency Medicine |
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: 1108367 Country of ref document: HK |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1108367 Country of ref document: HK |