CN100391956C - α晶形的雷奈酸锶、其制备方法和含有它的药物组合物 - Google Patents

α晶形的雷奈酸锶、其制备方法和含有它的药物组合物 Download PDF

Info

Publication number
CN100391956C
CN100391956C CNB2005100753929A CN200510075392A CN100391956C CN 100391956 C CN100391956 C CN 100391956C CN B2005100753929 A CNB2005100753929 A CN B2005100753929A CN 200510075392 A CN200510075392 A CN 200510075392A CN 100391956 C CN100391956 C CN 100391956C
Authority
CN
China
Prior art keywords
strontium ranelate
crystalline form
preparation
alpha crystalline
diffraction peak
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
Application number
CNB2005100753929A
Other languages
English (en)
Other versions
CN1754878A (zh
Inventor
S·霍瓦特
I·德米恩克
G·达米安
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.)
Laboratoires Servier SAS
Original Assignee
Laboratoires Servier SAS
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34942420&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN100391956(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Laboratoires Servier SAS filed Critical Laboratoires Servier SAS
Publication of CN1754878A publication Critical patent/CN1754878A/zh
Application granted granted Critical
Publication of CN100391956C publication Critical patent/CN100391956C/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Rheumatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Fodder In General (AREA)
  • Steroid Compounds (AREA)

Abstract

本发明涉及α晶形的式(I)的雷奈酸锶：其特征在于其X射线粉末衍射图谱和水含量为22至24%。本发明还涉及药物。

Description

α晶形的雷奈酸锶、其制备方法和含有它的药物组合物
本发明涉及α晶形的雷奈酸锶(strontium ranelate)、其制备方法以及含有它的药物组合物。
式(I)所示的雷奈酸锶：
Figure C20051007539200041
或5-[二(羧甲基)氨基]-3-羧甲基-4-氰基-2-噻吩甲酸的二锶盐及其水合物具有非常有价值的药理学和治疗特性，尤其是显著的抗骨质疏松特性，使得这些化合物可用于治疗和预防骨病。
雷奈酸锶及其水合物还具有使它们可用于治疗和预防关节病的特性。
在欧洲专利说明书EP0415850中已经描述了雷奈酸锶及其四水合物、七水合物和八水合物的制备和治疗用途。
在欧洲专利说明书EP 0813869中已经描述了雷奈酸锶在预防和治疗关节病中的用途。
本申请人现已发现雷奈酸锶可以以一种确定的晶形被获得，该晶形重现性良好，并且鉴于这一事实，该晶形在过滤和制剂制备容易性方面具有有价值的性质。
更具体而言，本发明涉及α晶形的雷奈酸锶，其特征在于水含量为22至24％和以下的X射线粉末衍射图谱，该衍射图谱用PANalytical X’Pert Pro衍射计和X’Celerator检测器测定并且以衍射峰位置(布拉格角2θ，以度表示)、衍射峰高(以计数表示)、衍射峰面积(以计数×度表示)、衍射峰半高宽(“FWHM”，以度表示)和晶面间距d(以
Figure C20051007539200042
表示)表示：
Figure C20051007539200051
Figure C20051007539200061
本发明还涉及制备α晶形的雷奈酸锶的方法，其特征在于将雷奈酸锶或其水合物在水中的溶液加热至回流，然后冷却直至结晶完全，并通过过滤收集产物。
●在本发明的制备方法中，可以使用通过任何方法获得的雷奈酸锶或其水合物，例如通过专利说明书EP 0415850中所述的制备方法获得的雷奈酸锶八水合物。
●获得所述晶形的一个优势是使得过滤非常迅速且有效，并且还使得可制备具有一致的且可重现的组成的药物制剂，当制剂用于口服施用时尤其有利。
●由此获得的晶形十分稳定，使得其在对温度、光、湿度或氧水平无特殊要求的条件下也可以贮存相当长的时间。
本发明还涉及包含作为活性成分的α晶形的雷奈酸锶以及一种或多种适宜的、惰性且无毒的赋形剂的药物细合物。在本发明的药物细合物中，可更特别地提及的是那些适于口服、胃肠外(静脉内或皮下)或鼻腔施用的药物组合物，如片剂或糖衣丸、颗粒剂、舌下片剂、胶囊剂、锭剂、栓剂、乳膏剂、软膏剂、皮肤凝胶剂、注射用制剂、可口服的混悬剂和口香糖。
有效剂量可根据病症的性质和严重程度、施用途径以及患者的年龄和体重而变化。剂量可以为每天0.2g至10g，一次或多次施用。
以下实施例对本发明进行了举例说明。
X射线粉末衍射图谱在以下实验条件下测定：
-PANalytical X’Pert Pro衍射计，X’Celerator检测器，
-电压45kV，电流强度40mA，
-支架(mounting)θ-θ，
-Kβ(Ni)滤波器，
-入射光和衍射光Soller狭缝：0.04rad，
-发散狭缝：自动，照射长度：10mm，
-掩膜(mask)：10mm，
-防散射狭缝：1/2°，
-测定模式：连续，从3°至34°，增量0.017°，
-每步测定时间：31.1秒，
-总时间：8分07秒，
-测定速度：0.068°/秒，
-旋转器：以1周/秒的速度旋转，
-测定温度：环境温度。
实施例1：α晶形的雷奈酸锶
将200g根据专利说明书EP 0415850中所述的方法获得的雷奈酸锶八水合物与2升水混合并加热至回流。然后将混合物冷却至20℃。通过过滤收集所获得的固体。
通过干燥失重法测得的所获得的产物的水含量为22至24％，相当于每分子雷奈酸锶含有8.1至9分子水。
X射线粉末衍射图谱：
α晶形的雷奈酸锶的X射线粉末衍射图谱(衍射角)以汇总在下表中的重要衍射峰给出：
Figure C20051007539200091
实施例2：药物组合物
制备1000片每片含有0.5g活性成分的片剂的处方：
实施例1的化合物............................................................658g
羧甲基淀粉钠..............................................................25.5g
微晶纤维素...............................................................119.4g
聚乙烯吡咯烷酮..............................................................38g
无水胶态二氧化硅...........................................................1.5g
硬脂酸镁...................................................................7.6g。

Claims (5)

1.α晶形的式(I)的雷奈酸锶：
其特征在于水含量为22至24％(重量)和以下的X射线粉末衍射图谱，该衍射图谱用PANalytical X’Pert Pro衍射计和X’Celerator检测器测定并且以采用度表示的衍射峰位置2θ、以计数表示的衍射峰高、以计数×度表示的衍射峰面积、以度表示的衍射峰半高宽和以
Figure C2005100753920002C2
表示的晶面间距d表示：
Figure C2005100753920003C1
2.制备权利要求1的α晶形的雷奈酸锶的方法，其特征在于将雷奈酸锶或其水合物在水中的溶液加热至回流，然后冷却至20℃，随后通过过滤收集产物。
3.包含作为活性成分的权利要求1的α晶形的雷奈酸锶以及与之组合的一种或多种可药用的、惰性且无毒的载体的药物组合物。
4.权利要求1的α晶形的雷奈酸锶在制备用于治疗或预防骨质疏松的药物中的用途。
5.权利要求1的α晶形的雷奈酸锶在制备用于治疗或预防关节病的药物中的用途。
CNB2005100753929A 2004-09-30 2005-06-16 α晶形的雷奈酸锶、其制备方法和含有它的药物组合物 Expired - Fee Related CN100391956C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0410335 2004-09-30
FR0410335A FR2875807B1 (fr) 2004-09-30 2004-09-30 Forme cristalline alpha du ranelate de strontium, son procede de preparation, et les compositions pharmaceutiques qui la contiennent

Publications (2)

Publication Number Publication Date
CN1754878A CN1754878A (zh) 2006-04-05
CN100391956C true CN100391956C (zh) 2008-06-04

Family

ID=34942420

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB2005100753929A Expired - Fee Related CN100391956C (zh) 2004-09-30 2005-06-16 α晶形的雷奈酸锶、其制备方法和含有它的药物组合物

Country Status (42)

Country Link
US (2) US7459568B2 (zh)
EP (2) EP1944302A1 (zh)
JP (2) JP2006104184A (zh)
KR (1) KR100816590B1 (zh)
CN (1) CN100391956C (zh)
AP (1) AP1930A (zh)
AR (1) AR049395A1 (zh)
AT (1) ATE411308T1 (zh)
AU (1) AU2005202718B2 (zh)
BR (1) BRPI0502228A (zh)
CA (1) CA2508824C (zh)
CO (1) CO5710195A1 (zh)
CR (1) CR7876A (zh)
CY (1) CY1108797T1 (zh)
DE (1) DE602005010359D1 (zh)
DK (1) DK1642897T3 (zh)
EA (1) EA008474B1 (zh)
EC (1) ECSP055859A (zh)
ES (1) ES2314593T3 (zh)
FR (1) FR2875807B1 (zh)
GE (1) GEP20074106B (zh)
GT (1) GT200500130A (zh)
HK (1) HK1086260A1 (zh)
HR (1) HRP20080652T3 (zh)
IL (1) IL169237A (zh)
MA (1) MA27815A1 (zh)
MX (1) MXPA05006407A (zh)
NO (1) NO333948B1 (zh)
NZ (1) NZ540802A (zh)
OA (1) OA13013A (zh)
PA (1) PA8638201A1 (zh)
PE (1) PE20060364A1 (zh)
PL (1) PL1642897T3 (zh)
PT (1) PT1642897E (zh)
RS (1) RS51110B (zh)
SA (1) SA05260168B1 (zh)
SG (1) SG121035A1 (zh)
SI (1) SI1642897T1 (zh)
TW (1) TWI367881B (zh)
UA (1) UA80008C2 (zh)
WO (1) WO2006035122A1 (zh)
ZA (1) ZA200504937B (zh)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2875807B1 (fr) * 2004-09-30 2006-11-17 Servier Lab Forme cristalline alpha du ranelate de strontium, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
US20070292529A1 (en) * 2006-06-19 2007-12-20 Tabbiner Philip S Strontium compositions and methods of treating osteoporotic conditions
US20070292535A1 (en) * 2006-06-19 2007-12-20 Tabbiner Philip S Strontium compositions and methods of treating arthritic and or osteoporitic conditions
CN101206208B (zh) * 2006-12-19 2011-08-10 北京德众万全药物技术开发有限公司 一种用hplc法分析雷尼酸锶原料及其制剂的方法
EP2346846A1 (en) 2008-09-29 2011-07-27 Ratiopharm GmbH Anhydrate and hydrate forms of strontium ranelate
IT1398542B1 (it) 2010-03-05 2013-03-01 Chemelectiva S R L Processo per la preparazione di un polimorfo
CN102241663B (zh) * 2010-05-10 2013-02-13 山东方明药业集团股份有限公司 一种雷奈酸锶八水合物的制备方法
WO2012143932A1 (en) * 2011-04-21 2012-10-26 Shilpa Medicare Limited Crystalline strontium ranelate form-s
CZ2011320A3 (cs) 2011-05-30 2012-12-12 Zentiva, K.S. Stabilní krystalická forma X stroncium ranelátu
EP2530068A1 (en) 2011-05-31 2012-12-05 Lacer, S.A. New strontium salts, synthesis and use thereof in the treatment of osteoporosis
US9301945B2 (en) 2011-07-21 2016-04-05 Emory University Methods for treating inflammatory conditions and states, and cancers by antagonizing NF-κB activation
CN102503931A (zh) * 2011-09-20 2012-06-20 浙江华海药业股份有限公司 一种雷尼酸锶晶形h的制备方法
WO2013113319A1 (en) * 2012-01-31 2013-08-08 Pharmathen S.A. Process for the preparation of strontium ranelate, intermediate or hydrates thereof
EP2641905A1 (en) 2012-03-23 2013-09-25 Urquima S.A. Solid forms of strontium ranelate and processes for their preparation
US8569514B1 (en) 2012-05-17 2013-10-29 Divi's Laboratories, Ltd. Process for the preparation of strontium ranelate

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5128367A (en) * 1989-09-01 1992-07-07 Adir Et Compagnie Divalent metal salts of 2-[N-N-di(carboxymethyl)amino]-3-cyano-4-carboxymethylthiophene-5-carboxylic acid
US5856356A (en) * 1996-06-17 1999-01-05 Adir Et Compagnie Use of strontium salts and pharmaceutical compositions thereof for the treatment of arthrosis
CN1496986A (zh) * 2002-09-24 2004-05-19 瑟维尔实验室 工业合成雷尼酸锶盐及其水合物的新方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL181304B1 (pl) 1994-07-22 2001-07-31 Lilly Co Eli Preparat farmaceutyczny do hamowania zmniejszania masy kosci PL PL PL PL PL PL PL PL PL PL
DE19642451A1 (de) 1996-10-15 1998-04-16 Merck Patent Gmbh Aminothiophencarbonsäureamide
IL161164A0 (en) * 2001-10-03 2004-08-31 Teva Pharma Preparation of levofloxacin and forms thereof
EP2272501B1 (en) * 2002-01-09 2013-03-20 Emisphere Technologies, Inc. Polymorphs of sodium 4-((4-chloro-2-hydroxybenzoyl) amino) butanoate
JP2006508909A (ja) * 2002-08-06 2006-03-16 テバ ファーマシューティカル インダストリーズ リミティド ガチフロキサシンの新規な結晶形
FR2844797B1 (fr) * 2002-09-24 2004-10-22 Servier Lab Nouveau procede de synthese industriel des tetraesters de l'acide 5-[bis (carboxymethyl)]-3-carboxymethyl-4-cyano-2- thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates
FR2844796A1 (fr) * 2002-09-24 2004-03-26 Servier Lab Nouveau procede de synthese industrielle du diester methylique de l'acide 5-amino-3-carboxymethyl-4-cyano-2- thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates
FR2875807B1 (fr) * 2004-09-30 2006-11-17 Servier Lab Forme cristalline alpha du ranelate de strontium, son procede de preparation, et les compositions pharmaceutiques qui la contiennent

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5128367A (en) * 1989-09-01 1992-07-07 Adir Et Compagnie Divalent metal salts of 2-[N-N-di(carboxymethyl)amino]-3-cyano-4-carboxymethylthiophene-5-carboxylic acid
US5856356A (en) * 1996-06-17 1999-01-05 Adir Et Compagnie Use of strontium salts and pharmaceutical compositions thereof for the treatment of arthrosis
CN1496986A (zh) * 2002-09-24 2004-05-19 瑟维尔实验室 工业合成雷尼酸锶盐及其水合物的新方法

Also Published As

Publication number Publication date
KR20060049966A (ko) 2006-05-19
AR049395A1 (es) 2006-07-26
BRPI0502228A (pt) 2006-05-09
EP1642897B9 (fr) 2009-08-12
JP2006104184A (ja) 2006-04-20
HK1086260A1 (en) 2006-09-15
EP1642897B1 (fr) 2008-10-15
GEP20074106B (en) 2007-05-10
ECSP055859A (es) 2006-09-18
US7459568B2 (en) 2008-12-02
WO2006035122A1 (fr) 2006-04-06
ZA200504937B (en) 2006-04-26
TWI367881B (en) 2012-07-11
AU2005202718A1 (en) 2006-04-13
CY1108797T1 (el) 2014-04-09
MA27815A1 (fr) 2006-04-03
DK1642897T3 (da) 2009-01-26
ES2314593T3 (es) 2009-03-16
GT200500130A (es) 2005-12-20
FR2875807A1 (fr) 2006-03-31
RS51110B (sr) 2010-10-31
IL169237A (en) 2010-12-30
JP2010132669A (ja) 2010-06-17
CR7876A (es) 2007-12-10
PA8638201A1 (es) 2006-05-16
US7745482B2 (en) 2010-06-29
NO20052998L (no) 2006-03-31
DE602005010359D1 (de) 2008-11-27
OA13013A (fr) 2006-11-10
AU2005202718B2 (en) 2010-09-16
NZ540802A (en) 2006-11-30
HRP20080652T3 (en) 2009-01-31
SI1642897T1 (sl) 2009-02-28
TW200610758A (en) 2006-04-01
US20080312314A1 (en) 2008-12-18
CA2508824A1 (fr) 2006-03-30
CN1754878A (zh) 2006-04-05
PT1642897E (pt) 2008-11-27
FR2875807B1 (fr) 2006-11-17
US20060069271A1 (en) 2006-03-30
PE20060364A1 (es) 2006-06-17
SG121035A1 (en) 2006-04-26
CO5710195A1 (es) 2006-12-29
SA05260168B1 (ar) 2009-02-25
NO333948B1 (no) 2013-10-28
PL1642897T3 (pl) 2009-04-30
EA008474B1 (ru) 2007-06-29
ATE411308T1 (de) 2008-10-15
EP1642897A1 (fr) 2006-04-05
EA200500842A1 (ru) 2006-04-28
NO20052998D0 (no) 2005-06-17
AP1930A (en) 2008-12-15
UA80008C2 (uk) 2007-08-10
EP1944302A1 (fr) 2008-07-16
CA2508824C (fr) 2009-03-24
AP2005003323A0 (en) 2005-06-30
MXPA05006407A (es) 2006-04-05
KR100816590B1 (ko) 2008-03-24

Similar Documents

Publication Publication Date Title
CN100391956C (zh) α晶形的雷奈酸锶、其制备方法和含有它的药物组合物
CN100402502C (zh) 盐酸伊伐布雷定的γ-晶形、其制备方法和含有它的药物组合物
CN100404512C (zh) 盐酸伊伐布雷定的βd-晶形、其制备方法和含有它的药物组合物
TW386081B (en) Opioid compounds
CN110049987A (zh) 制备(s)-n-(5-((r)-2-(2，5-二氟苯基)吡咯烷-1-基)-吡唑并[1，5-a]嘧啶-3-基)-3-羟基吡咯烷-1-甲酰胺及其盐的方法
EP0158532A2 (en) Use of 4-amino-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chloro-2-methoxybenzamide for the manufacture of a medicament having anti-emetic activity.
BRPI0609962B1 (pt) Composição farmacêutica oral
CN101955440B (zh) 一种阿戈美拉汀新晶型及其制备方法
CA1284953C (en) 2-alkoxy-n-(1-azabicyclo[2.2.2] oct-3-yl) benzamides and thiobenzamides in amethod for alleviating emesis caused by non-platinum anticancer drugs
CN101805289A (zh) 伊伐布雷定盐酸盐的ω-晶型、其制备方法和药物组合物
JP6826993B2 (ja) 複素環化合物およびその使用方法
AU2007215363A1 (en) Use of gallium(III) complexes for the treatment of melanomas
TWI285204B (en) Polymorphs of a crystalline azabicyclo[2,2.2]octan-3-amine citrate and their pharmaceutical compositions
AU742544B2 (en) Basic aluminum magnesium carbonate, method for the preparation thereof and its use as a pharmaceutical composition for treating stomach acidity
CN115671107B (zh) 用于解酒的复方药物组合物
US5091547A (en) Phenylacetic acid derivative and process for making same
JPH1112191A (ja) エタノール吸収阻害剤
KR0143994B1 (ko) 페닐아세트산 유도체 및 그의 제조방법
RU2008125299A (ru) Кристаллические f-, g-, h-, i- и к-формы иматинибмезилата
EP2266948A1 (en) Salts of tramadol and diflunisal and their crystal form in the treatment of pain
JPH06271467A (ja) ロキサチジン−アルギン酸配合体を有効成分とする抗潰瘍薬
JPH0826999A (ja) 消化器不定愁訴の予防または治療薬
JPH02221257A (ja) トリプトファン誘導体の製造方法
CN1183274A (zh) 乳酸铋类络合物及抗组胺药构成的复合的制备及制剂

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: 1086260

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: 1086260

Country of ref document: HK

C56 Change in the name or address of the patentee

Owner name: FRENCH SERVIER PHARMACEUTICAL FACTORY

Free format text: FORMER NAME: SERVIER LAB

CP01 Change in the name or title of a patent holder

Address after: Kolb tile

Patentee after: LES LABORATOIRES SERVIER

Address before: Kolb tile

Patentee before: Laboratoires Therwill

CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20080604

Termination date: 20170616