CN1318065A - 新的邦托拉唑盐 - Google Patents

新的邦托拉唑盐 Download PDF

Info

Publication number
CN1318065A
CN1318065A CN99809800A CN99809800A CN1318065A CN 1318065 A CN1318065 A CN 1318065A CN 99809800 A CN99809800 A CN 99809800A CN 99809800 A CN99809800 A CN 99809800A CN 1318065 A CN1318065 A CN 1318065A
Authority
CN
China
Prior art keywords
pantoprazole
magnesium
magnesium dihydrate
sesquialter hydrate
dihydrate
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.)
Granted
Application number
CN99809800A
Other languages
English (en)
Other versions
CN1146558C (zh
Inventor
B·科尔
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.)
Takeda GmbH
Nycomed Asset Management GmbH
Nycomed Germany Holding GmbH
Original Assignee
Byk Gulden Lomberg Chemische Fabrik GmbH
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=7881823&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN1318065(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Byk Gulden Lomberg Chemische Fabrik GmbH filed Critical Byk Gulden Lomberg Chemische Fabrik GmbH
Publication of CN1318065A publication Critical patent/CN1318065A/zh
Application granted granted Critical
Publication of CN1146558C publication Critical patent/CN1146558C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicinal Preparation (AREA)
  • Detergent Compositions (AREA)
  • Manufacture And Refinement Of Metals (AREA)
  • Drying Of Gases (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)

Abstract

本发明涉及邦托拉唑的镁盐二水合物。

Description

新的邦托拉唑盐
发明主题
本发明涉及活性化合物邦托拉唑(pantoprazole)的新盐。该新盐可用于制备药物的医药工业。
现有技术
如公开在EP-A-0005129、EP-A-0166287、EP-A-0174726和EP-A-0268956中的吡啶-2-基甲基亚磺酰基-1H-苯并咪唑类，由于其抑制H+/K+ ATP酶的作用，所以它们在治疗由胃酸分泌增多引起的疾病中具有相当大的重要性。商业上可得到的这类活性化合物的实例包括5-甲氧基-2-[(4-甲氧基-3,5-二甲基-2-吡啶基)甲基亚磺酰基]-1H-苯并咪唑(INN：奥美拉唑)、5-二氟甲氧基-2-[(3,4-二甲氧基-2-吡啶基)甲基亚磺酰基]-1H-苯并咪唑(INN：邦托拉唑)、2-{[3-甲基-4-(2,2,2-三氟乙氧基)-2-吡啶基]甲基亚磺酰基}-1H-苯并咪唑(INN：兰索拉唑)和2-{[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基亚磺酰基}-1H-苯并咪唑(INN：蜡伯拉唑)。
上述吡啶-2-基甲基亚磺酰基-1H-苯并咪唑类的共同性能在于这些活性化合物对酸敏感，这一性能对于其效力终究是必不可少的；由此可见，这些化合物在中性，特别是酸性环境下，具有强烈的分解趋势，生成明显着色的分解产物。
在过去，尽管吡啶-2-基甲基亚磺酰基-1H-苯并咪唑类具有酸敏感性，但是为了得到包含这些吡啶-2-基甲基亚磺酰基-1H-苯并咪唑类的稳定且可存放的口服剂型，人们已经付出了相当大的努力，至今不能得到这类稳定且可存放的口服剂型(如片剂或胶囊剂)。为了使得给药剂型在极端贮存条件下(如在高温和高大气湿度的热带地区)具有合适的贮存稳定性，这些口服剂型的制备是比较复杂的，而且在包装时需要采取一些措施。
国际专利申请WO97/41114公开了制备吡啶-2-基甲基亚磺酰基-1H-苯并咪唑类的镁盐的特定方法，特别是还通过实施例描述了邦托拉唑镁盐的制备方法。根据所表明的分析数据，制得的镁盐为无水形式的镁盐。
发明描述
人们现已发现邦托拉唑的镁盐二水合物具有惊人的稳定性能，这种稳定性能使得其可特别适用于固体或口服剂型。不论是与邦托拉唑本身相比，还是与邦托拉唑钠倍半水合物(自从1994年以来，这种活性化合物已出现在市场上，欧洲专利0589981)相比，或者是与邦托拉唑钠一水合物(用于工业制备的中间体形式，欧洲专利0533790)相比，吡啶-2-基甲基亚磺酰基-1H-苯并咪唑类的镁盐二水合物均显示出了显著改进的稳定性能。
邦托拉唑镁二水合物在90℃下完全稳定4天，显示出几乎没有变色或分解；而邦托拉唑钠倍半水合物和一水合物在相同时间内变成红褐色，生成了相当数量的分解产物。
本发明涉及邦托拉唑的镁盐二水合物(邦托拉唑镁二水合物)。
邦托拉唑镁二水合物可用于治疗和预防被认为通过使用吡啶-2-基甲基亚磺酰基-1H-苯并咪唑类得到治疗或缓解的所有疾病。特别地，邦托拉唑镁二水合物可用于治疗胃部疾病。
基于其溶解性能，邦托拉唑镁二水合物可应用于目前必须借助于特定药物制备的情形。因此，邦托拉唑镁二水合物特别适用于其中活性化合物在相对长时期内释放和吸收的情形(参见如欧洲专利申请0841903)。通过将邦托拉唑的镁盐与钠盐结合，可获得能够得到含所需活性化合物量的血液的溶液。
邦托拉唑镁二水合物可通过本身已知的方法制备，在水或水与极性有机溶剂(如醇，优选乙醇或异丙醇，或酮类，如丙酮或丁酮)的混合物中，将邦托拉唑或易溶解的邦托拉唑盐(如邦托拉唑钠)与镁盐反应。
可用于该方法中的合适镁盐包括，如氯化镁、溴化镁、氟化镁、碘化镁、甲酸镁、乙酸镁、3-戊酮镁、硫酸镁、葡糖酸镁或碳酸镁。镁的醇盐(如甲醇镁、乙醇镁、(异)丙醇镁、丁醇镁、己醇镁或苯酚镁)或氢氧化镁也可在水合介质中与邦托拉唑或邦托拉唑钠反应。
实施例
二[5-[二氟甲氧基]-2-[[3,4-二甲氧基-2-吡啶基]甲基]亚磺酰基]-1H-苯并咪唑烷]镁二水合物
在20-25℃下，于搅拌容器中，将3.85kg(8.9mol)邦托拉唑钠倍半水合物[[5-[二氟甲氧基]-2-[[3,4-二甲氧基-2-吡啶基]甲基]亚磺酰基]-1H-苯并咪唑烷]钠倍半水合物]溶解在38.5升纯水中。在搅拌条件下，于20-30℃下，在3至4小时内，加入于8升纯水中的1.0kg(4.90mol)二氯化镁六水合物溶液。在进一步搅拌18小时后，离心沉淀的固体，利用23升纯水洗涤，在20-30℃下，于35升纯水中搅拌1至2小时，再离心，再用30-50升水洗涤。将固体产物在50℃下真空(30-50mbar)干燥，直至得到＜4.8％的残留水含量。再研磨产物。
得到白色至米色的粉末状标题化合物，该化合物可直接用于下一步的药物制备。
收率：3.40kg(理论值为90％)；水含量：4.5-4.6％；熔点：194-196℃，分解。
CHN分析     C     H     N     S
理论值     46.58     3.91     10.19     7.77
实测值     46.33     3.89     10.04     7.83
使用有机溶剂与水的混合物，标题化合物可由另一种方法制备。为此，在50-60℃下溶解邦托拉唑钠倍半水合物。逐滴加入溶于水的0.5摩尔当量镁盐(如氯化镁六水合物)，允许在搅拌条件下冷却溶液。过滤沉淀的固体，利用对应的有机溶剂洗涤，在50℃下真空干燥至恒重。得到无色粉末状标题化合物。不同溶剂的实例如下述表1所示。
表1：
邦托拉唑钠倍半水合物 有机溶剂  水  标题化合物收率  熔点℃  水含量％
50g 异丙醇300ml  300ml  45.4g  196-197  4.4-4.5
50g 异丙醇300ml  120ml  45.9g  196-197  4.3
50g 乙醇300ml  300ml  45.8g  197-198  4.6
50g 丙酮300ml  300ml  45.6g  195-196  4.6-4.7
例如，根据下述方式，将邦托拉唑与碱式镁盐(如甲基化镁)反应，可通过另一种方法制备标题化合物：在60-70℃下，将90g邦托拉唑溶解在700ml 2-丙醇中；加入13.4g(0.5mol)固体甲基化镁，允许在搅拌条件下冷却溶液并过滤；再加入36ml水后过滤所形成的结晶固体，利用水洗涤，在50℃下真空干燥至恒重，得到熔点为194-196℃(水含量为4.8％)的米色固体标题化合物。

Claims (8)

1、邦托拉唑镁二水合物。
2、包含邦托拉唑镁二水合物及常规辅料的药物。
3、邦托拉唑镁二水合物用于治疗胃或肠疾病的用途。
4、包含邦托拉唑镁二水合物和邦托拉唑钠倍半水合物的组合药物。
5、包含邦托拉唑镁二水合物和邦托拉唑钠倍半水合物的组合药物，其中邦托拉唑镁二水合物与邦托拉唑钠倍半水合物的重量比例(基于邦托拉唑)为：10％邦托拉唑镁二水合物和90％邦托拉唑钠倍半水合物至90％邦托拉唑镁二水合物和10％邦托拉唑钠倍半水合物。
6、包含邦托拉唑镁二水合物和邦托拉唑钠倍半水合物的组合药物，其中邦托拉唑镁二水合物与邦托拉唑钠倍半水合物的重量比例(基于邦托拉唑)为：25％邦托拉唑镁二水合物和75％邦托拉唑钠倍半水合物至75％邦托拉唑镁二水合物和25％邦托拉唑钠倍半水合物。
7、包含邦托拉唑镁二水合物和邦托拉唑钠倍半水合物的组合药物，其中邦托拉唑镁二水合物与邦托拉唑钠倍半水合物的重量比例(基于邦托拉唑)为：40％邦托拉唑镁二水合物和60％邦托拉唑钠倍半水合物至60％邦托拉唑镁二水合物和40％邦托拉唑钠倍半水合物。
8、包含邦托拉唑镁二水合物和邦托拉唑钠倍半水合物的组合药物，其中邦托拉唑镁二水合物与邦托拉唑钠倍半水合物的重量比例(基于邦托拉唑)为：50％邦托拉唑镁二水合物和50％邦托拉唑钠倍半水合物。
CNB998098000A 1998-08-18 1999-08-12 新的邦托拉唑盐 Expired - Fee Related CN1146558C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19843413A DE19843413C1 (de) 1998-08-18 1998-08-18 Neue Salzform von Pantoprazol
DE19843413.8 1998-08-18

Publications (2)

Publication Number Publication Date
CN1318065A true CN1318065A (zh) 2001-10-17
CN1146558C CN1146558C (zh) 2004-04-21

Family

ID=7881823

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB998098000A Expired - Fee Related CN1146558C (zh) 1998-08-18 1999-08-12 新的邦托拉唑盐

Country Status (33)

Country Link
US (2) US6410569B1 (zh)
EP (1) EP1105386B1 (zh)
JP (1) JP2002523411A (zh)
KR (1) KR100657835B1 (zh)
CN (1) CN1146558C (zh)
AT (1) ATE219074T1 (zh)
AU (1) AU761715B2 (zh)
BG (1) BG65255B1 (zh)
BR (1) BR9914288A (zh)
CA (1) CA2341031C (zh)
CZ (1) CZ293734B6 (zh)
DE (3) DE19843413C1 (zh)
DK (1) DK1105386T3 (zh)
EA (1) EA004431B1 (zh)
EE (1) EE04278B1 (zh)
ES (1) ES2178896T3 (zh)
HK (1) HK1037616A1 (zh)
HR (1) HRP20010117B1 (zh)
HU (1) HU226618B1 (zh)
IL (3) IL141328A0 (zh)
ME (1) ME00562A (zh)
MX (1) MXPA01001758A (zh)
NO (1) NO319782B1 (zh)
NZ (1) NZ509761A (zh)
PL (1) PL198801B1 (zh)
PT (1) PT1105386E (zh)
RS (1) RS50071B (zh)
SI (1) SI1105386T1 (zh)
SK (1) SK285105B6 (zh)
TR (1) TR200100287T2 (zh)
UA (1) UA58605C2 (zh)
WO (1) WO2000010995A1 (zh)
ZA (1) ZA200100934B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100457104C (zh) * 2003-07-23 2009-02-04 尼科梅德有限责任公司 质子泵抑制剂的碱性盐

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19843413C1 (de) * 1998-08-18 2000-03-30 Byk Gulden Lomberg Chem Fab Neue Salzform von Pantoprazol
MY137726A (en) 2000-11-22 2009-03-31 Nycomed Gmbh Freeze-dried pantoprazole preparation and pantoprazole injection
TW200410955A (en) 2002-07-29 2004-07-01 Altana Pharma Ag Novel salt of (S)-PANTOPRAZOLE
DE10234617B4 (de) * 2002-07-29 2013-04-04 Nycomed Gmbh Neues Salz von (S)-Pantoprazol
CA2510849A1 (en) * 2002-12-19 2004-07-08 Teva Pharmaceutical Industries Ltd Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates
AU2004237362A1 (en) * 2003-05-06 2004-11-18 Altana Pharma Ag Proton pump inhibitors for the treatment of lower abdominal disorders
CL2004000983A1 (es) * 2003-05-08 2005-03-04 Altana Pharma Ag Composicion farmaceutica oral en forma de tableta que comprende a pantoprazol magnetico dihidratado, en donde la forma de tableta esta compuesto por un nucleo, una capa intermedia y una capa exterior; y uso de la composicion farmaceutica en ulceras y
PE20050150A1 (es) * 2003-05-08 2005-03-22 Altana Pharma Ag Una forma de dosificacion que contiene (s)-pantoprazol como ingrediente activo
CN1791406A (zh) * 2003-05-19 2006-06-21 普利瓦研究与发展有限公司 5－(二氟甲氧基)－2－[[(3,4－二甲氧基－2－吡啶基)甲基]亚硫酰基]－1h－苯并咪唑(泮托拉唑)钠水络合物的固态形式
EP1615913A2 (en) 2003-06-10 2006-01-18 Teva Pharmaceutical Industries Limited Process for preparing 2-(pyridinyl)methyl sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole
WO2005012289A1 (en) * 2003-07-17 2005-02-10 Altana Pharma Ag Novel salt of (r) - pantoprazole
DK1651217T3 (da) * 2003-07-23 2008-06-16 Nycomed Gmbh Alkalisalte af protonpumpeinhibitorer
CA2554260A1 (en) * 2004-01-28 2005-08-18 Altana Pharma Ag Calcium, potassium, zinc, lithium and aluminium salts of pantoprazole and (s)-pantoprazole
WO2005074898A2 (en) * 2004-01-28 2005-08-18 Altana Pharma Ag Composition comprising (s) pantoprazole and an antibiotic for treating helicobacter pylori
WO2005074932A1 (en) * 2004-01-28 2005-08-18 Altana Pharma Ag The use of (s) - pantoprazole magnesium for the treatment of airway disorders
WO2005074930A1 (en) * 2004-01-28 2005-08-18 Altana Pharma Ag Pharmaceutical combinations of (s) -pantoprazole with nsaid or corticosteroids
WO2005074931A1 (en) * 2004-01-28 2005-08-18 Altana Pharma Ag Pharmaceutical combinations comprising (s) -pantoprazole
EP1716136A1 (en) * 2004-02-11 2006-11-02 Ulkar Kimya Sanayii Ve Ticaret A.S. Pyridine benzimidazole sulfoxides of high purity
WO2005082888A1 (en) * 2004-03-01 2005-09-09 Milen Merkez Ilac Endustrisi A.S. Process for the preparation of magnesium salt of omeprazole
JP2007536349A (ja) * 2004-05-07 2007-12-13 ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規の医薬剤形及び製造方法
WO2007041790A1 (en) * 2005-10-14 2007-04-19 Jon Pty Limited Salts of proton pump inhibitors and process for preparing same
WO2007146341A2 (en) 2006-06-12 2007-12-21 Teva Pharmaceutical Industries Ltd. Amorphous and crystalline forms of pantoprazole magnesium salt
WO2008057559A1 (en) * 2006-11-06 2008-05-15 Teva Pharmaceutical Industries Ltd. Processes for preparing substantially pure pantoprazole magnesium
EP3187494A1 (en) * 2015-12-30 2017-07-05 KRKA, tovarna zdravil, d.d., Novo mesto Process for the preparation of pantoprazole sodium sesquihydrate
EP3397630B1 (en) * 2015-12-30 2021-05-26 KRKA, tovarna zdravil, d.d., Novo mesto Process for the preparation of pantoprazole sodium sesquihydrate

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE7804231L (sv) * 1978-04-14 1979-10-15 Haessle Ab Magsyrasekretionsmedel
IL75400A (en) * 1984-06-16 1988-10-31 Byk Gulden Lomberg Chem Fab Dialkoxypyridine methyl(sulfinyl or sulfonyl)benzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same
JPS6150978A (ja) * 1984-08-16 1986-03-13 Takeda Chem Ind Ltd ピリジン誘導体およびその製造法
FI90544C (fi) * 1986-11-13 1994-02-25 Eisai Co Ltd Menetelmä lääkeaineina käyttökelpoisten 2-pyridin-2-yyli-metyylitio- ja sulfinyyli-1H-bensimidatsolijohdannaisten valmistamiseksi
DE4018642C2 (de) * 1990-06-11 1993-11-25 Byk Gulden Lomberg Chem Fab Neue Salzform des 5-Difluormethoxy-2-[(3,4-dimethoxy-2-pyridyl) methylsulfinyl]-1H-benzimitazol-Natriumsalzes
YU48263B (sh) * 1991-06-17 1997-09-30 Byk Gulden Lomberg Chemische Fabrik Gmbh. Postupak za dobijanje farmaceutskog preparata na bazi pantoprazola
SE9302396D0 (sv) * 1993-07-09 1993-07-09 Ab Astra A novel compound form
SE9600070D0 (sv) * 1996-01-08 1996-01-08 Astra Ab New oral pharmaceutical dosage forms
SE508669C2 (sv) * 1996-04-26 1998-10-26 Astra Ab Nytt förfarande
DE19843413C1 (de) * 1998-08-18 2000-03-30 Byk Gulden Lomberg Chem Fab Neue Salzform von Pantoprazol

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100457104C (zh) * 2003-07-23 2009-02-04 尼科梅德有限责任公司 质子泵抑制剂的碱性盐

Also Published As

Publication number Publication date
BR9914288A (pt) 2001-06-19
TR200100287T2 (tr) 2001-07-23
HUP0103257A3 (en) 2003-01-28
EA200100208A1 (ru) 2001-08-27
US6686379B2 (en) 2004-02-03
CA2341031C (en) 2006-04-04
CA2341031A1 (en) 2000-03-02
KR100657835B1 (ko) 2006-12-15
BG105173A (en) 2001-11-30
ME00562B (me) 2011-12-20
DE122005000049I1 (de) 2006-12-28
HRP20010117B1 (en) 2010-07-31
DE19843413C1 (de) 2000-03-30
AU5515699A (en) 2000-03-14
SK2362001A3 (en) 2001-09-11
NO20010718L (no) 2001-02-12
US6410569B1 (en) 2002-06-25
EE200100054A (et) 2002-06-17
PT1105386E (pt) 2002-11-29
MXPA01001758A (es) 2002-04-17
RS50071B (sr) 2009-01-22
NO20010718D0 (no) 2001-02-12
EA004431B1 (ru) 2004-04-29
NO319782B1 (no) 2005-09-12
ZA200100934B (en) 2002-03-04
CN1146558C (zh) 2004-04-21
HU226618B1 (en) 2009-04-28
IL141328A0 (en) 2002-03-10
DK1105386T3 (da) 2002-09-30
WO2000010995A1 (en) 2000-03-02
EP1105386A1 (en) 2001-06-13
HUP0103257A2 (hu) 2002-02-28
IL141157A0 (en) 2002-02-10
ES2178896T3 (es) 2003-01-01
KR20010072487A (ko) 2001-07-31
US20020188008A1 (en) 2002-12-12
DE69901840D1 (de) 2002-07-18
BG65255B1 (bg) 2007-10-31
ME00562A (en) 2011-12-20
DE122005000049I2 (de) 2007-03-29
DE69901840T2 (de) 2003-05-22
NZ509761A (en) 2003-08-29
CZ293734B6 (cs) 2004-07-14
EE04278B1 (et) 2004-04-15
JP2002523411A (ja) 2002-07-30
AU761715B2 (en) 2003-06-05
ATE219074T1 (de) 2002-06-15
PL198801B1 (pl) 2008-07-31
YU11301A (sh) 2003-12-31
UA58605C2 (uk) 2003-08-15
SI1105386T1 (en) 2002-12-31
IL141157A (en) 2007-06-17
HRP20010117A2 (en) 2002-02-28
SK285105B6 (sk) 2006-06-01
HK1037616A1 (en) 2002-02-15
EP1105386B1 (en) 2002-06-12
PL345993A1 (en) 2002-01-14
CZ2001621A3 (cs) 2001-08-15

Similar Documents

Publication Publication Date Title
CN1146558C (zh) 新的邦托拉唑盐
RU2105773C1 (ru) Способ получения стабильных в кислой среде производных бензимидазола
EP0124495B1 (en) Omeprazole salts
SE445353B (sv) Inneslutningskomplex baserat pa cyklodextrin och indometacin, sett att framstella komplexet samt farmaceutisk beredning derav
CN101233111A (zh) 4-（3-氯-4-（环丙基氨基羰基）氨基苯氧基）-7-甲氧基-6-喹啉羧酸酰胺的无定形盐及其制备方法
CN104169270A (zh) 达比加群酯甲磺酸盐的固体形式以及它们的制备方法
CN110035750B (zh) 药物组合物和使用方法
WO2005040106A1 (en) Thiourea derivative-containing pharmaceutical composition having improved solubility and bioavailability
US20050272818A1 (en) Novel process for producing Ibuprofen sodium dihydrate
WO2007074996A1 (en) Stable pharmaceutical composition containing s-omeprazole and a method of manufacturing the same
HUT64979A (en) Method for producing (carboxy)-alkoxy-alkyl derivatives of cyclodextrines
EP1742667A1 (en) Stable pharmaceutical composition containing benzimidazole derivatives and method of manufacturing the same
JPS6163695A (ja) プリマイシン塩、その製造法および医薬組成物
JP3990728B2 (ja) Ｎ−［４−オキソ−２−（１ｈ−テトラゾール−５−イル）−４ｈ−１−ベンゾピラン−８−イル］−４−（４−フェニルブトキシ）ベンズアミドの塩
CN1048984C (zh) 晶形1呋喃硝胺氢氯化物的制备
CN100457104C (zh) 质子泵抑制剂的碱性盐
US8362041B2 (en) Pharmacologically active compounds containing sulfur
JP2004331646A (ja) 結晶性ｌ−アスパラギン酸カルシウムの製造方法
CN104109148A (zh) 新拉唑类化合物或其盐及其制备方法和用途
JP2006298943A (ja) 結晶性ｌ−アスパラギン酸カルシウムの製造方法

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C56 Change in the name or address of the patentee

Owner name: NICOMEDES LIMITED LIABILITY COMPANY

Free format text: FORMER NAME OR ADDRESS: OTANA MEDICINE AG

CP03 Change of name, title or address

Address after: Konstanz

Patentee after: NYCOMED GmbH

Address before: Konstanz

Patentee before: ALTANA PHARMA AG

C56 Change in the name or address of the patentee

Owner name: NYCOMED INC.

Free format text: FORMER NAME: NYCOMED GMBH

CP01 Change in the name or title of a patent holder

Address after: Konstanz

Patentee after: Nycomed GmbH

Address before: Konstanz

Patentee before: Nycomed GmbH

C56 Change in the name or address of the patentee

Owner name: TAKEDA GMBH

Free format text: FORMER NAME: NYCOMED INC.

CP01 Change in the name or title of a patent holder

Address after: Konstanz

Patentee after: TAKEDA GmbH

Address before: Konstanz

Patentee before: Nycomed GmbH

ASS Succession or assignment of patent right

Owner name: NYCOMED ASSET MANAGEMENT GMBH

Free format text: FORMER OWNER: TAKEDA GMBH

Effective date: 20150619

Owner name: NYCOMED GERMANY HOLDING GMBH

Free format text: FORMER OWNER: NYCOMED ASSET MANAGEMENT GMBH

Effective date: 20150619

C41 Transfer of patent application or patent right or utility model
C56 Change in the name or address of the patentee

Owner name: TAKEDA GMBH

Free format text: FORMER NAME: NYCOMED GERMANY HOLDING GMBH

CP01 Change in the name or title of a patent holder

Address after: Konstanz

Patentee after: TAKEDA GmbH

Address before: Konstanz

Patentee before: Nycomed Germany holding LLC

TR01 Transfer of patent right

Effective date of registration: 20150619

Address after: Konstanz

Patentee after: Nycomed Germany holding LLC

Address before: Konstanz

Patentee before: Nycomed asset management LLC

Effective date of registration: 20150619

Address after: Konstanz

Patentee after: Nycomed asset management LLC

Address before: Konstanz

Patentee before: TAKEDA GmbH

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

Granted publication date: 20040421

Termination date: 20180812

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