CN100422143C - 那格列奈b型结晶的制造方法 - Google Patents

那格列奈b型结晶的制造方法 Download PDF

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CN100422143C
CN100422143C CNB018212999A CN01821299A CN100422143C CN 100422143 C CN100422143 C CN 100422143C CN B018212999 A CNB018212999 A CN B018212999A CN 01821299 A CN01821299 A CN 01821299A CN 100422143 C CN100422143 C CN 100422143C
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nateglinide
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澄川通人
丸尾诚
宫崎和雄
仁科重宏
松泽由纪子
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    • C07—ORGANIC CHEMISTRY
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Abstract

提供包括在低温下将那格列奈(nateglinide)的溶剂化物湿润结晶干燥到溶剂消失之后使之结晶转变的工序的、制造实质上不含有H型结晶的那格列奈B型结晶的方法。根据此方法可以在工业规模上制造那格列奈B型结晶的单一结晶。

Description

那格列奈B型结晶的制造方法
发明领域
本发明涉及有效的糖尿病药物那格列奈(nateglinide)[化学名：N-(反式-4-异丙基环己基羰基)-D-苯基丙氨酸；N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine]的制造方法。更详细说，本发明涉及实质上不含有H型结晶的那格列奈B型结晶的制造方法。
背景技术
已经知道，那格列奈是一种有效的糖尿病治疗药物，口服显示优异的降血糖作用(特公平4-15221号公报)。
又，已经知道，那格列奈具有多种结晶形态，其中的H型结晶是有用的。然而，为了离析出H型结晶，就必须严格地控制晶析条件，很谨慎地进行晶析，存在难以晶析操作的问题(参见专利第2508949号)。
另一方面，其它结晶形态之一的B型结晶，具有在晶析时通过进行冷却晶析而可容易地制造的优点。然而，此B型结晶在制造阶段有可能转变成H型结晶，事实在工业规模制造那格列奈时，判明所得到的B型结晶中混入有H型结晶。作为药品使用的那格列奈，尽可能避免结晶多形的混入为好，如果可能的话，单一晶形为最好，因此希望开发可以提供只含有此B型结晶的医药制剂的、没有结晶多形混入的那格列奈B型结晶的制造方法。
发明内容
本发明的目的在于提供工业制造没有混入其它晶形的那格列奈B型结晶的方法。
本发明人以有效利用那格列奈B型结晶为目的进行研究的结果，发现通过选择那格列奈制造阶段的条件就可以以工业规模制造单一晶形的那格列奈B型结晶，至此完成了本发明。
即，本发明提供包括在低温下将那格列奈的溶剂化物湿润结晶干燥到溶剂消失之后使之结晶转变的工序的、实质上不含有H型结晶的那格列奈B型结晶的制造方法。
本发明提供，理想情况是，将含有由含那格列奈的溶液通过冷却晶析而析出得到的那格列奈水合物的溶剂化物在50℃以下的温度干燥到溶剂消失、溶剂化物实质上消除之后，加热至60℃～110℃，使之向B型结晶结晶转变的工序的、制造实质上不含有H型结晶的那格列奈B型结晶的方法。
实施发明的最佳方案
作为本发明所使用的那格列奈的溶剂化物湿润结晶，列举有，甲醇、乙醇和异丙醇等醇类、乙酸甲酯或乙酸乙酯等乙酸酯类、或水的溶剂化物。作为那格列奈的溶剂化物湿润结晶，通常使用醇合物和水合物等。在用乙醇合物的场合，例如通过在60％乙醇水中加入那格列奈并使其达到5重量％的浓度，在30℃左右溶解之后，把它冷却到10℃以下而可制备。
其中，水合物由于是在那格列奈的醇溶液、优选乙醇溶液中加入水，冷却到10℃以下而晶析出，所以通过分离它就可以容易得到，因此优选。
所得到的溶剂化物的湿润结晶，使之干燥到溶剂消失。此时的温度根据附着在结晶上的溶剂的种类和数量的不同而不同，但通常在60℃以下，优选在50℃以下为。温度的下限没有特别的限制，但是从经济观点考虑，通常在20℃以上进行。干燥通常在减压下为好，工业上尽可能提高减压度时以短时间完成干燥。
在低温的干燥继续到溶剂实质上消失为止，但没有必要完全消失，即使残留5重量％左右的溶剂，由于在结晶转变时也消失所以也没有问题。
所得到的干燥结晶通过加热到60℃～110℃、优选70℃～100℃，使其转变成B型结晶。结晶转变通常进行0.5～48小时为好，更优选1～24小时。
B型结晶中的H型结晶通过使用DSC而可分析。那格列奈B型结晶在用DSC测定时，检测不到H型结晶为好。
湿润状态的那格列奈溶剂化物结晶干燥的场合，在实验室规模的小规模的情况下，由于分离结晶时的残留溶剂量少，并且达到干燥器的最高减压的速度快，所以即使从初期阶段提高干燥温度也没有大的问题，但在工业规模下，例如，平均1次制造5kg以上的情况下，在从晶析液分离的结晶中残留的溶剂量多，并且干燥时到达最高减压度的时间比较长，因此，通过使用本发明的方法制造不含有H型结晶的B型结晶成为可能。
下面通过实施例来更具体地说明本发明，但是本发明并不限于这些实施例。
实施例1
把24.5kg的那格列奈H型结晶加入到360L乙醇中，在室温下搅拌使之溶解。向其中加入240L水，在确认溶解之后，冷却到5℃，再在5℃下熟化1小时。分离析出的结晶，得到湿结晶43.0kg。把它放在盘式干燥器中，于45℃干燥24小时(水分含量约1重量％)，再在90℃加热12小时，使之结晶转变，得到干燥结晶13.3kg。测定此结晶的DSC的结果，检测出了B型结晶特有的峰(熔点约130℃)，但没有检测出H型结晶特有的峰(熔点约139℃)，因此结论是所得到的结晶只是B型结晶，实质上不含有H型结晶。
比较例1
把37.0kg的那格列奈H型结晶加入到540L乙醇中，在室温下搅拌使之溶解。向其中加入360L水，在确认溶解之后，冷却到5℃，再在5℃下熟化1小时。分离析出的结晶，得到湿结晶46.7kg。把它放在锥形干燥器中，于30℃干燥3小时(水分含量约10重量％)，再在90℃加热12小时，使之结晶转变，得到干燥结晶25.9kg。测定此结晶的DSC的结果，除了B型结晶之外，还观察到H型结晶的峰。
比较例2
把37.0kg的那格列奈H型结晶加入到540L乙醇中，在室温下搅拌使之溶解，向其中加入360L水，在确认溶解之后，冷却到5℃，再在5℃下熟化1小时。分离析出的结晶，得到湿结晶44.5kg。把它放在锥形干燥器中，于30℃干燥3小时(水分含量约10重量％)，再在90℃加热15小时，使之结晶转变，得到干燥B型结晶26.6kg。测定此结晶的DSC的结果，除了B型结晶之外，还观察到H型结晶的峰。
通过使用本发明的条件，以工业规模制造不存在其它晶型的那格列奈B型结晶成为可能，廉价地提供以单一那格列奈结晶的形式含有那格列奈B型结晶的医药制剂成为可能。

Claims (7)

1. 一种实质上不含有H型结晶的那格列奈B型结晶的制造方法，包括在60℃以下的温度干燥那格列奈溶剂化物湿润结晶，直至其中含有5重量％以下的溶剂，再通过将其加热到60～110℃来进行结晶转变。
2. 根据权利要求1所述的那格列奈B型结晶的制造方法，其中在50℃或以下的温度进行干燥。
3. 根据权利要求1所述的那格列奈B型结晶的制造方法，其中进行干燥直到实质上溶剂消失为止。
4. 根据权利要求1所述的那格列奈B型结晶的制造方法，其中前述溶剂化物湿润结晶是水合物.
5. 根据权利要求1所述的那格列奈B型结晶的制造方法，其中加热到70～110℃来进行结晶转变。
6. 根据权利要求1所述的那格列奈B型结晶的制造方法，其中，那格列奈溶剂化物湿润结晶的低温干燥和结晶转变这两个工序是在工业规模下进行的工序.
7. 如权利要求1-6中任一项所述的实质上不含有H型结晶的那格列奈B型结晶的制造方法，其中起始的溶剂化物湿润结晶含有那格列奈水合物并且是在冷却的条件下由含那格列奈的溶液晶析出而获得的.
CNB018212999A 2000-10-24 2001-10-23 那格列奈b型结晶的制造方法 Expired - Fee Related CN100422143C (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104402756A (zh) * 2014-11-27 2015-03-11 天方药业有限公司 一种高纯度那格列奈的制备方法

Families Citing this family (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2001241168B2 (en) * 2000-03-17 2005-06-16 Ajinomoto Co., Inc. Drugs for complications of diabetes and neuropathy and utilization thereof
KR100783306B1 (ko) * 2000-10-18 2007-12-10 아지노모토 가부시키가이샤 아실페닐알라닌의 제조방법
CN1232502C (zh) * 2000-10-18 2005-12-21 味之素株式会社 那格列胺结晶的制备方法
MXPA03003685A (es) * 2000-10-24 2004-01-26 Ajinomoto Kk Preparaciones que contienen nateglinida.
KR100829410B1 (ko) * 2000-10-24 2008-05-15 아지노모토 가부시키가이샤 나테글리니드 함유 친수성 의약 제제
WO2003087039A1 (fr) * 2002-04-15 2003-10-23 Ajinomoto Co., Inc. Nouveau cristal de nateglinide
US7411089B2 (en) 2002-04-15 2008-08-12 Ajinomoto Co., Inc. Nateglinide crystals
US6861553B2 (en) 2002-07-03 2005-03-01 Teva Pharmaceuticals Industries Ltd. Process for preparing nateglinide and intermediates thereof
US7534913B2 (en) 2002-07-18 2009-05-19 Teva Pharmaceutica Industries Ltd. Crystalline form of nateglinide
CA2492644A1 (en) * 2002-07-18 2004-01-29 Teva Pharmaceutical Industries Ltd. Polymorphic forms of nateglinide
US7358390B2 (en) 2002-07-18 2008-04-15 Teva Pharmaceutical Industries Ltd. Polymorphic forms of nateglinide
US7420084B2 (en) 2002-07-18 2008-09-02 Teva Pharmaceutical Industries Ltd. Polymorphic forms of nateglinide
US7148376B2 (en) 2002-07-18 2006-12-12 Teva Pharmaceutical Industries Ltd. Polymorphic forms of nateglinide
DE60310734T2 (de) * 2003-11-26 2007-10-11 A.M.S.A. Anonima Matèrie Sintètiche e Affini S.p.A. Verfahren zur Herstellung von Nateglinid in der B-Form
CA2563793A1 (en) * 2004-05-07 2005-11-24 Teva Pharmaceutical Industries Ltd. Polymorphic forms of nateglinide
WO2005110395A1 (en) * 2004-05-19 2005-11-24 University Of South Carolina System and device for magnetic drug targeting with magnetic drug carrier particles
WO2005113485A2 (en) * 2004-05-20 2005-12-01 Dr. Reddy's Laboratories Ltd. Stable nateglinide form b compositions
US7425648B2 (en) 2005-01-03 2008-09-16 A.M.S.A. Anonima Materie Sintetiche E. Affini S.P.A. Process for the preparation of nateglinide, preferably in B-form
WO2006080524A1 (ja) * 2005-01-31 2006-08-03 Ajinomoto Co., Inc. 血糖降下剤を含有する、耐糖能異常、境界型糖尿病、インスリン抵抗性及び高インスリン血症の改善ないし治療用医薬組成物
WO2007135533A1 (en) * 2006-05-23 2007-11-29 Aurobindo Pharma Limited Process for preparing nateglinide b-type crystals
KR100837843B1 (ko) * 2006-12-26 2008-06-13 씨제이제일제당 (주) 나테글리나이드 결정형, 그 제조방법, 및 그를 포함하는약제학적 조성물
US9150499B2 (en) 2010-06-14 2015-10-06 Cipla Limited Process for the preparation of nateglinide
WO2014037832A2 (en) 2012-09-06 2014-03-13 Mahesh Kandula Compositions and methods for the treatment of epilepsy and neurological diseases
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US9321716B1 (en) 2014-11-05 2016-04-26 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic syndrome
US9290486B1 (en) 2014-11-05 2016-03-22 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy
US9175008B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Prodrugs of anti-platelet agents
US9173877B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Compositions and methods for the treatment of local pain
US9932294B2 (en) 2014-12-01 2018-04-03 Cellix Bio Private Limited Compositions and methods for the treatment of multiple sclerosis
US9206111B1 (en) 2014-12-17 2015-12-08 Cellix Bio Private Limited Compositions and methods for the treatment of neurological diseases
CN109369443A (zh) * 2018-11-05 2019-02-22 扬子江药业集团江苏海慈生物药业有限公司 一种新的那格列奈h晶型的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5463116A (en) * 1991-07-30 1995-10-31 Ajinomoto Co., Inc. Crystals of N- (trans-4-isopropylcyclohexlycarbonyl)-D-phenylalanine and methods for preparing them

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6354321A (ja) * 1985-03-27 1988-03-08 Ajinomoto Co Inc 血糖降下剤
JP2508949B2 (ja) * 1991-07-30 1996-06-19 味の素株式会社 Ｎ−（トランス−４−イソプロピルシクロヘキシルカルボニル）−ｄ−フェニルアラニンの結晶及びその製造法
EP2277517A1 (en) * 1996-11-15 2011-01-26 Ajinomoto Co., Inc. Nateglinide tablet composition
US6844006B1 (en) * 1999-07-09 2005-01-18 Pennfield Oil Company Process and apparatus for the preparation of chlortetracycline-containing animal feed compositions
PL356300A1 (en) * 1999-12-28 2004-06-28 Ajinomoto Co, Inc. Oral preparations for diabetes
AU2001241168B2 (en) * 2000-03-17 2005-06-16 Ajinomoto Co., Inc. Drugs for complications of diabetes and neuropathy and utilization thereof
CN1232502C (zh) * 2000-10-18 2005-12-21 味之素株式会社 那格列胺结晶的制备方法
KR100783306B1 (ko) * 2000-10-18 2007-12-10 아지노모토 가부시키가이샤 아실페닐알라닌의 제조방법
MXPA03003685A (es) * 2000-10-24 2004-01-26 Ajinomoto Kk Preparaciones que contienen nateglinida.
US7411089B2 (en) * 2002-04-15 2008-08-12 Ajinomoto Co., Inc. Nateglinide crystals

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5463116A (en) * 1991-07-30 1995-10-31 Ajinomoto Co., Inc. Crystals of N- (trans-4-isopropylcyclohexlycarbonyl)-D-phenylalanine and methods for preparing them

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104402756A (zh) * 2014-11-27 2015-03-11 天方药业有限公司 一种高纯度那格列奈的制备方法
CN104402756B (zh) * 2014-11-27 2016-08-31 天方药业有限公司 一种高纯度那格列奈的制备方法

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