CN101643432B - 获得v晶形阿戈美拉汀的新方法 - Google Patents
获得v晶形阿戈美拉汀的新方法 Download PDFInfo
- Publication number
- CN101643432B CN101643432B CN2009101603077A CN200910160307A CN101643432B CN 101643432 B CN101643432 B CN 101643432B CN 2009101603077 A CN2009101603077 A CN 2009101603077A CN 200910160307 A CN200910160307 A CN 200910160307A CN 101643432 B CN101643432 B CN 101643432B
- Authority
- CN
- China
- Prior art keywords
- crystalline form
- agomelatine
- compound
- obtaining
- preparation formula
- 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.)
- Expired - Fee Related
Links
- YJYPHIXNFHFHND-UHFFFAOYSA-N agomelatine Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(OC)=CC=C21 YJYPHIXNFHFHND-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 229960002629 agomelatine Drugs 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000007789 gas Substances 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052802 copper Inorganic materials 0.000 claims description 3
- 239000010949 copper Substances 0.000 claims description 3
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 238000000889 atomisation Methods 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 description 7
- 238000005507 spraying Methods 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 0 COc1ccc(cccc2CC*)c2c1 Chemical compound COc1ccc(cccc2CC*)c2c1 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/08—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Pregnancy & Childbirth (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Gynecology & Obstetrics (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Battery Electrode And Active Subsutance (AREA)
- Manufacture Of Metal Powder And Suspensions Thereof (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
Abstract
本发明涉及获得V晶形阿戈美拉汀的新方法。更具体地讲,本发明涉及获得式(I)化合物的V晶形的方法。
Description
技术领域
本发明涉及获得式(I)的阿戈美拉汀或N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺的V晶形的新方法:
背景技术:
阿戈美拉汀或N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺具有有价值的药理学性质。
实际上,其具有双重特性,其一方面是褪黑激素能系统受体的激动剂,另一方面,其又是5-HT2C受体的拮抗剂。这些性质使其具有中枢神经系统活性,并且更尤其是使其具有治疗重症抑郁、季节性情感障碍、睡眠障碍、心血管病状、消化系统病状、由于时差导致的失眠和疲劳、食欲障碍和肥胖的活性。
已经在欧洲专利EP 0 447 285中对阿戈美拉汀、其制备以及其在治疗中的应用进行了描述。
鉴于这种化合物的药用价值,以极佳的纯度获得这种化合物,并且尤其是以具有使其可在对温度、光照、湿度或氧气水平没有特殊要求的情况下长期储存的有价值特性的可充分再现形式获得这种化合物是很重要的。
专利申请EP 1 752 443描述了一种定义明确的阿戈美拉汀结晶形式-V晶形,其特征在于下面的X-射线粉末衍射图,该衍射图是用SiemensD5005衍射仪(铜对阴极)进行测量的,并且以晶面间距d、Bragg′s角2θ和相对强度(表示为相对于最强线的百分比)进行表达:
这种以可再现方式获得的明确定义的晶形具有很有价值的形态学性质,尤其是具有远远高于所述其它形式的比表面积。然而,其储存稳定期很短,并且在所有的情况中,都低于6个月。
发明内容
申请人现在研制了一种以可充分再现的方式获得V晶形形式的阿戈美拉汀的新方法,籍此增加了其随着时间的流逝的稳定性。因此,这种新方法使得可以获得具有与其药学应用相容的性质的V晶形形式的阿戈美拉汀。过去仅能通过所谓的“高能”研磨或通过用已经用研磨获得的结构纯净的形式进行种晶来获得V晶形。
申请人现在令人吃惊地发现,可以用喷雾干燥来获得这种形式。事实上,喷雾干燥是一种用于获得小粒度固体颗粒的常用技术。所得物质常常是无定形的(药学工业中的无定形状态,多晶型现象(Amorphous state,Polymorphism in pharmaceutical industry),R.Hilfiker编辑,Wiley-VCHWeinheim 2006,第X章,第259-285页,S.Petit和G.Coquerel)。与其相反,在本发明中,可以用喷雾干燥来获得一种定义明确的晶形-V型,并且该晶形具有更好的随着时间的流逝的稳定性。
更具体地讲,本发明涉及一种获得V晶形形式的式(I)的阿戈美拉汀的新方法,该方法的特征在于在喷雾干燥器中将溶解于一种或两种可以以任意比例混溶并且沸点低于120℃的溶剂中的阿戈美拉汀溶液雾化。
喷雾干燥是一种在农业、食品和药学领域中常用的技术,用其来对被喷洒穿越热气体的溶液进行干燥。在实践中,用于干燥溶液的气体是空气,但一些使用有机溶剂的制药方法需要用惰性气体作为干燥气体以避免某些分解过程。
本发明的结晶操作优选地是用喷雾干燥器来进行的。本发明的雾化更优选地是根据使用具有平行流并且更优选地具有并向流(即,喷雾的溶液和干燥气流处于同一个方向上)的喷嘴的雾化原理来进行的。
所用气体有利地是压缩空气或惰性气体,例如氮气。
用于本发明方法的优选溶剂有乙醇、水、异丙醚、甲醇、乙酸乙酯或丙酮。
所用阿戈美拉汀溶液的最小浓度为5g/l,并且更优选使用10g/l的溶液。
本发明方法的入口温度有利地为70℃至120℃。
在本发明的结晶方法中,可以使用用任何方法获得的式(I)的阿戈美拉汀。
具体实施方式
用下文的实施例对本发明进行非限制性说明。
实施例1:N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺的V晶形
将阿戈美拉汀在乙醇/异丙醚混合物(50/50:v/v)中的10g/l的溶液引入到BUCHI 190小型喷雾干燥器的雾化器中。干燥室的入口温度为90℃,出口温度为66℃。在收集碗中回收被雾化了的粉末并用下面的晶体学数据对其进行鉴定:
1)用Siemens D5005衍射仪获得的图谱,使用3°-30 °的2θ角范围,0.04°的跨距且每个跨距4秒:
-晶胞的晶体结构:单斜晶,
-空间群:P21/n
-晶胞中分子的数目:8(Z’=2)
2)下面的X-射线粉末衍射图,其是用Siemens D5005衍射仪(铜对阴极)测得的,并且以晶面间距d、Bragg′s角2θ和相对强度(表示为相对于最强线的百分比)进行表达:
实施例2:通过雾化获得的N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺的V晶形随着时间的流逝的稳定性
将1g实施例1获得的化合物的样品放置在常规储存条件下:环境压力和温度。在21个月后,所得样品的衍射图没有发生变化,其仍然具有所得V晶形的特性。
Claims (4)
2.如权利要求1所述的制备式(I)化合物的V晶形的方法,其特征在于所用溶剂是乙醇和异丙醚。
3.如权利要求1所述的制备式(I)化合物的V晶形的方法,其特征在于所用气体是氮气。
4.如权利要求1所述的制备式(I)化合物的V晶形的方法,其特征在于所用阿戈美拉汀溶液的最小浓度为5g/l。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR08/04466 | 2008-08-05 | ||
FR0804466A FR2934856B1 (fr) | 2008-08-05 | 2008-08-05 | Nouveau procede d'obtention de la forme cristalline v de l'agomelatine |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101643432A CN101643432A (zh) | 2010-02-10 |
CN101643432B true CN101643432B (zh) | 2012-12-12 |
Family
ID=40418877
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2009101603077A Expired - Fee Related CN101643432B (zh) | 2008-08-05 | 2009-08-05 | 获得v晶形阿戈美拉汀的新方法 |
Country Status (46)
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101781226B (zh) * | 2009-12-23 | 2012-03-28 | 天津泰普药品科技发展有限公司 | 阿戈美拉汀及其药物组合物 |
WO2012093402A1 (en) * | 2011-01-04 | 2012-07-12 | Symed Labs Limited | Processes for the preparation of n-[2-(7-methoxy-1-naphthyl)ethyl]acetamide |
WO2012130837A1 (en) | 2011-03-28 | 2012-10-04 | Ratiopharm Gmbh | Solid agomelatine in non-crystalline form |
CA2877410A1 (en) | 2012-07-16 | 2014-01-23 | Ratiopharm Gmbh | Complex of agomelatine and cyclodextrin |
WO2015124496A1 (en) | 2014-02-19 | 2015-08-27 | Synthon B.V. | Pharmaceutical composition comprising amorphous agomelatine |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5194614A (en) * | 1990-02-27 | 1993-03-16 | Adir Et Compagnie | Compounds having a naphthalene structure |
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 |
CN1907957A (zh) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | 阿戈美拉汀的新晶形ⅳ、它的制备方法和包含它的药物组合物 |
CN1907959A (zh) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | 阿戈美拉汀的新晶形ⅲ、它的制备方法和包含它的药物组合物 |
CN1907958A (zh) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | 阿戈美拉汀的新晶形ⅴ、它的制备方法和包含它的药物组合物 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SU1703641A1 (ru) * | 1988-02-23 | 1992-01-07 | Ростовский государственный университет | Способ получени 3,5-ди-трет.бутил-4-оксиацетанилида |
YU48420B (sh) * | 1991-03-25 | 1998-07-10 | Hoechst Aktiengesellschaft | Postupak za dobijanje biološki razgradljivih mikročestica sa dugotrajnim delovanjem |
US20080280991A1 (en) * | 2007-05-08 | 2008-11-13 | Auspex Pharmaceuticals, Inc. | Substituted naphthalenes |
FR2923482B1 (fr) * | 2007-11-09 | 2010-01-29 | Servier Lab | Nouvelle forme cristalline vi de l'agomelatine, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
-
2008
- 2008-08-05 FR FR0804466A patent/FR2934856B1/fr not_active Expired - Fee Related
-
2009
- 2009-07-23 SG SG200904973-5A patent/SG158830A1/en unknown
- 2009-07-23 PE PE2009000980A patent/PE20100153A1/es not_active Application Discontinuation
- 2009-07-24 CR CR10952A patent/CR10952A/es unknown
- 2009-07-27 AU AU2009203071A patent/AU2009203071B2/en not_active Ceased
- 2009-07-27 AP AP2009004936A patent/AP3196A/xx active
- 2009-07-28 UY UY0001032014A patent/UY32014A/es not_active Application Discontinuation
- 2009-07-28 IL IL200126A patent/IL200126A/en active IP Right Grant
- 2009-07-29 MY MYPI20093144 patent/MY151042A/en unknown
- 2009-07-29 SV SV2009003345A patent/SV2009003345A/es active IP Right Grant
- 2009-07-29 MX MX2009008046A patent/MX2009008046A/es active IP Right Grant
- 2009-07-30 NI NI200900154A patent/NI200900154A/es unknown
- 2009-07-30 ZA ZA200905334A patent/ZA200905334B/en unknown
- 2009-07-31 MA MA32130A patent/MA31223B1/fr unknown
- 2009-07-31 CO CO09080220A patent/CO6120151A1/es active IP Right Grant
- 2009-07-31 GT GT200900215A patent/GT200900215A/es unknown
- 2009-08-02 SA SA109300499A patent/SA109300499B1/ar unknown
- 2009-08-02 JO JO2009286A patent/JO2812B1/en active
- 2009-08-03 EC EC2009009554A patent/ECSP099554A/es unknown
- 2009-08-03 CL CL2009001685A patent/CL2009001685A1/es unknown
- 2009-08-03 ME MEP-2009-258A patent/ME00929B/me unknown
- 2009-08-03 NZ NZ578826A patent/NZ578826A/en not_active IP Right Cessation
- 2009-08-03 CA CA2674770A patent/CA2674770C/fr not_active Expired - Fee Related
- 2009-08-03 GE GEAP200911402A patent/GEP20125408B/en unknown
- 2009-08-04 PT PT09290608T patent/PT2151430E/pt unknown
- 2009-08-04 AT AT09290608T patent/ATE518825T1/de active
- 2009-08-04 ES ES09290608T patent/ES2371047T3/es active Active
- 2009-08-04 KR KR1020090071644A patent/KR101118335B1/ko active IP Right Grant
- 2009-08-04 AR ARP090102984A patent/AR074889A1/es unknown
- 2009-08-04 WO PCT/FR2009/000974 patent/WO2010015747A1/fr active Application Filing
- 2009-08-04 SI SI200930075T patent/SI2151430T1/sl unknown
- 2009-08-04 RS RS20110403A patent/RS52002B/en unknown
- 2009-08-04 UA UAA200908223A patent/UA102816C2/ru unknown
- 2009-08-04 PL PL09290608T patent/PL2151430T3/pl unknown
- 2009-08-04 DK DK09290608.0T patent/DK2151430T3/da active
- 2009-08-04 EP EP09290608A patent/EP2151430B1/fr active Active
- 2009-08-04 TW TW098126203A patent/TW201008901A/zh unknown
- 2009-08-04 BR BRPI0903058-1A patent/BRPI0903058A2/pt not_active Application Discontinuation
- 2009-08-04 US US12/462,470 patent/US8252957B2/en active Active
- 2009-08-04 EA EA200900944A patent/EA016896B1/ru not_active IP Right Cessation
- 2009-08-05 HN HN2009001437A patent/HN2009001437A/es unknown
- 2009-08-05 CN CN2009101603077A patent/CN101643432B/zh not_active Expired - Fee Related
- 2009-08-05 JP JP2009182090A patent/JP5047240B2/ja not_active Expired - Fee Related
-
2010
- 2010-08-09 HK HK10107580.9A patent/HK1141005A1/xx not_active IP Right Cessation
-
2011
- 2011-08-04 CY CY20111100751T patent/CY1111873T1/el unknown
- 2011-10-05 HR HR20110712T patent/HRP20110712T1/hr unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5194614A (en) * | 1990-02-27 | 1993-03-16 | Adir Et Compagnie | Compounds having a naphthalene structure |
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 |
CN101041629A (zh) * | 2004-02-13 | 2007-09-26 | 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 |
CN1907957A (zh) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | 阿戈美拉汀的新晶形ⅳ、它的制备方法和包含它的药物组合物 |
CN1907959A (zh) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | 阿戈美拉汀的新晶形ⅲ、它的制备方法和包含它的药物组合物 |
CN1907958A (zh) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | 阿戈美拉汀的新晶形ⅴ、它的制备方法和包含它的药物组合物 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101643432B (zh) | 获得v晶形阿戈美拉汀的新方法 | |
Veverka et al. | Cocrystals of quercetin: synthesis, characterization, and screening of biological activity | |
CN109734690B (zh) | 新abexinostate盐、相关的晶体形式、其制备方法以及含有其的药物组合物 | |
JP2015044844A (ja) | エルトロンボパグ及びエルトロンボパグ塩の多形体、並びにその調製方法 | |
Shi et al. | Improving the Solubility and Dissolution of Ibrutinib by preparing Solvates | |
JP2011105685A (ja) | フェネチルアミン化合物の結晶 | |
CN103833755A (zh) | 阿哌沙班晶型b及其制备方法 | |
CN103864690B (zh) | 伊伐布雷定盐酸盐的s晶型、其制备方法和药物组合物 | |
WO2010081341A1 (zh) | N-正丙基-3-(4-甲基苯基)-4-(4-甲磺酰基苯基)-2,5-二氢吡咯-2-酮的i型结晶及其制造方法 | |
CN106831524B (zh) | 一种手性吡咯烷酮乙酰胺衍生物及其制备方法和用途 | |
KR20220120638A (ko) | (s)-1-(1-아크릴로일피롤리딘-3-일)-3-((3,5-디메톡시페닐)에티닐)-5-(메틸아미노)-1h-피라졸-4-카르복사미드의 결정질 형태 | |
AU2010344330B2 (en) | Novel polymorph of the hydrochloride of the (4-hydroxycarbamoyl-phenyl)-carbamic acid (6-diethylamino methyl-2-naphtalenyl) ester | |
WO2021129651A1 (zh) | 2-[4-[(e)-(2-酮环己烯基)甲基]苯基]丙酸的晶型及其制备方法 | |
CN105669476A (zh) | 一种盐酸多巴酚丁胺晶型及其制备方法和应用 | |
Veverka et al. | Crystal habit modifications of imatinib mesylate under various precipitation conditions | |
WO2010084502A1 (en) | A crystalline form of orlistat and a process thereof | |
FR2541996A1 (fr) | Derives de benzamide | |
CN109796400B (zh) | 一种甲苯磺酸索拉菲尼晶型及其制备方法 | |
Patel et al. | Antimicrobial screening of synthesized some novel azomethines via organic base | |
Zhong et al. | Trapping of Isocyanates with Benzotriazole in situ-Preparation of Carbamoyl Benzotriazoles as an Isocyanate Alternative via Curtius Rearrangement | |
WO2021038590A1 (en) | Novel polymorph of ribociclib succinate | |
Rather et al. | N-Methyl-N-arylformamides: Synthesis and Interaction of with Carbonic Anhydrase (PDB: 3FW3) and Nuclease (PDB: 6O70) Enzymes via In Silico Molecular Docking | |
Chu et al. | Novel phenylamino acetamide derivatives as potent and selective κ opioid receptor agonists | |
CN111454170A (zh) | 一种乙酰苯胺类化合物及其制备方法和应用 | |
CN111423363A (zh) | 一种1/10水马来酸氯苯那敏化合物及其药物组合物 |
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: 1141005 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: 1141005 Country of ref document: HK |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121212 Termination date: 20210805 |
|
CF01 | Termination of patent right due to non-payment of annual fee |