CN104829572B - 达格列净新晶型及其制备方法 - Google Patents

达格列净新晶型及其制备方法 Download PDF

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CN104829572B
CN104829572B CN201410046371.3A CN201410046371A CN104829572B CN 104829572 B CN104829572 B CN 104829572B CN 201410046371 A CN201410046371 A CN 201410046371A CN 104829572 B CN104829572 B CN 104829572B
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dapagliflozin
crystal forms
novel crystal
preparation
drying
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CN104829572A (zh
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朱希风
李孝壁
张添程
袁阜平
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Jiangsu Hansoh Pharmaceutical Group Co Ltd
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Priority to PCT/CN2015/071009 priority patent/WO2015117538A1/zh
Priority to US15/117,533 priority patent/US9550747B2/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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
    • C07D309/10—Oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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Abstract

本发明涉及达格列净新晶型及其制备方法。具体而言，本发明涉及式（I）的达格列净的新晶型，这种晶型在以2θ角度和晶面间距（d值）表示的X‑射线粉末衍射图谱中在约4.318（20.45）处具有特征吸收峰，可以通过将达格列净溶解在良性有机溶剂中，再加入不良溶剂搅拌析晶，过滤，干燥而制得。本发明的达格列净新晶型具有以下优良特性：溶解性好，引湿性小，稳定性高，制备可重现性好。

Description

达格列净新晶型及其制备方法
技术领域
本发明属于多晶型药物制备技术领域，具体涉及一种达格列净的新晶型及其制备方法。
背景技术
达格列净（Dapagliflozin）是由Bristol-Myers Squibb/AstraZeneca开发的，用于治疗II型糖尿病的药物（钠-葡萄糖协同转运蛋白-2（SGLT-2）抑制剂）。
2010年12月，Bristol-Myers Squibb/AstraZeneca向EMA提交申请。2012年4月，欧洲人用药务委员会推荐批准达格列净用于治疗II型糖尿病的申请。
2010年12月，同样向FDA提交申请。2012年1月，FDA发出回应函，要求增加临床数据。
达格列净（Dapagliflozin），化学名为2-氯-5-(β-D-吡喃葡萄糖-1-基)-4’-乙氧基二苯甲烷，其化学结构如下：
到目前为止，在有关达格列净晶型方面的报道中，仅有原研晶型专利（CN101479287）报道了9种晶型：其为达格列净溶剂化物和达格列净氨基酸络合物，均被保护。具体内容如下：
发明内容
本发明的目的在于提供一种新的、特异的达格列净晶型。
本发明的如式（I）所示的达格列净的新晶型的XRPD图谱如图1所示，
该晶型在以2θ角度和晶面间距（d值）表示的X-射线粉末衍射图谱中在约4.318（20.45）处具有特征吸收峰。
本发明的另一目的在于提供一种本发明所述的达格列净的新晶型的制备方法，包括在0℃～30℃温度下，达格列净在有机溶剂体系中制得。
优选的，将达格列净溶解在良性有机溶剂中，加入不良溶剂，然后搅拌析晶，过滤，于0～30℃干燥，即得目标晶型。
更优选的，所述良性有机溶剂选自醚类溶剂，优选乙醚或甲基叔丁基醚。
更优选的，所述不良有机溶剂选自烷烃类溶剂，优选正己烷或正庚烷。
优选的，反应温度为10～20℃。
优选的，搅拌析晶时间为1.5～2小时。
优选的，干燥温度为10～30℃。
优选的，所述干燥为真空干燥。
进一步地，制备达格列净无定型晶型的方法为：将达格列净溶解良性有机溶剂中，再加入达格列净不良溶剂，搅拌析晶，经过滤、干燥，制得达格列净无定型晶型。
进一步地，采取的具体方案如下：将达格列净溶解在良性有机溶剂中，再加入达格列净不良溶剂，加完后在30℃以下继续搅拌析晶1.5～2小时，过滤，0～30℃真空干燥，即得达格列净无定型晶型样品。
本发明提供了一种制备达格列净无定型晶型的新方法，该方法具有溶解性好、引湿性小、工艺稳定、可操作性强、收率高、制备可重现性好等优点。
附图说明
图1为达格列净新晶型的X-射线粉末衍射谱图。
具体实施方式
实施例1：达格列净新晶型的制备
称取达格列净（0.5g），加入乙醚（4.5ml）中，搅拌溶清，加入正己烷（20ml），瓶壁有白色油状物粘附，继续搅拌，1.5h后过滤、抽干，得0.42g产物（白色粉末状固体）。经XRPD测定，图谱如图1所示。
实施例2：达格列净新晶型的制备
称取达格列净（0.5g），加入甲基叔丁基醚（3ml）中，搅拌溶清，加入正己烷（10ml），瓶壁有白色油状物粘附，继续搅拌，2h后过滤、抽干，得0.33g产物（白色粉末状固体）。经XRPD测定，图谱如图1所示。
实施例3：达格列净新晶型的制备
称取达格列净（0.5g），加入甲基叔丁基醚（3ml）中，搅拌溶清，加入正庚烷（10ml），瓶壁有白色油状物粘附，继续搅拌，2h后过滤、抽干，得0.35g产物（白色粉末状固体）。经XRPD测定，图谱如图1所示。

Claims (6)

1.制备达格列净新晶型的方法，其特征在于：在0℃～30℃温度下，将达格列净溶解在乙醚中，加入正己烷，然后搅拌析晶，1.5小时后过滤，0～30℃干燥，即得，其中达格列净新晶型的XRPD图谱如图1所示。
2.制备达格列净新晶型的方法，其特征在于：在0℃～30℃温度下，将达格列净溶解在甲基叔丁基醚中，加入正己烷，然后搅拌析晶，2小时后过滤，0～30℃干燥，即得，其中达格列净新晶型的XRPD图谱如图1所示。
3.制备达格列净新晶型的方法，其特征在于：在0℃～30℃温度下，将达格列净溶解在甲基叔丁基醚中，加入正庚烷，然后搅拌析晶，2小时后过滤，0～30℃干燥，即得，其中达格列净新晶型的XRPD图谱如图1所示。
4.根据权利要求1-3任意一项所述的制备方法，其特征在于：反应温度为10～20℃。
5.根据权利要求1-3任意一项所述的制备方法，其特征在于：干燥温度为10～30℃。
6.根据权利要求1-3任意一项所述的制备方法，其特征在于：所述干燥为真空干燥。
CN201410046371.3A 2014-02-10 2014-02-10 达格列净新晶型及其制备方法 Active CN104829572B (zh)

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CN201580006892.9A CN106170482B (zh) 2014-02-10 2015-01-19 达格列净新特晶型及其制备方法
PCT/CN2015/071009 WO2015117538A1 (zh) 2014-02-10 2015-01-19 达格列净新特晶型及其制备方法
US15/117,533 US9550747B2 (en) 2014-02-10 2015-01-19 Dapagliflozin crystalline form and preparation method thereof
TW104104348A TWI711626B (zh) 2014-02-10 2015-02-10 達格列淨新穎特別晶型及其製備方法

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US7919598B2 (en) 2006-06-28 2011-04-05 Bristol-Myers Squibb Company Crystal structures of SGLT2 inhibitors and processes for preparing same
AR065809A1 (es) 2007-03-22 2009-07-01 Bristol Myers Squibb Co Formulaciones farmaceuticas que contienen un inhibidor sglt2
US9845303B2 (en) 2015-10-19 2017-12-19 Cadila Healthcare Limited Process for the preparation of dapagliflozin
JP7007300B2 (ja) * 2016-05-24 2022-01-24 江▲蘇▼豪森▲薬▼▲業▼集▲団▼有限公司 ダパグリフロジンの新規な結晶形並びにその製造方法および用途
CN107445932A (zh) * 2016-05-30 2017-12-08 上海医药工业研究院 达格列净共晶物的制备工艺
US11427555B2 (en) * 2016-08-09 2022-08-30 Laurus Labs Limited Processes for preparation of dapagliflozin or its solvates or co-crystals thereof
KR20180058510A (ko) * 2016-11-24 2018-06-01 한미약품 주식회사 다파글리플로진 l-프롤린을 포함하는 약제학적 제제
WO2018124497A1 (ko) * 2016-12-30 2018-07-05 한미약품 주식회사 다파글리플로진 l-프롤린과 항당뇨병제를 포함하는 약제학적 복합 제제
US11020412B2 (en) 2017-03-16 2021-06-01 Inventia Healthcare Limited Pharmaceutical composition comprising dapagliflozin
CN108516966A (zh) * 2017-10-19 2018-09-11 浙江海正药业股份有限公司 达格列净的晶型及其制备方法和用途
CN110790735A (zh) * 2018-08-03 2020-02-14 北京海晶生物医药科技有限公司 一种达格列净新晶型n及其制备方法
CN111559997A (zh) * 2019-02-13 2020-08-21 罗欣药业(上海)有限公司 一种达格列净新晶型及其制备方法
CN111689936A (zh) * 2019-03-15 2020-09-22 罗欣药业(上海)有限公司 达格列净新晶型及其制备方法

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US6515117B2 (en) * 1999-10-12 2003-02-04 Bristol-Myers Squibb Company C-aryl glucoside SGLT2 inhibitors and method
US7919598B2 (en) * 2006-06-28 2011-04-05 Bristol-Myers Squibb Company Crystal structures of SGLT2 inhibitors and processes for preparing same
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CA2837232A1 (en) * 2011-06-03 2012-12-06 Ratiopharm Gmbh Pharmaceutical composition comprising dapagliflozin and cyclodextrin
EP2597090A1 (en) * 2011-11-28 2013-05-29 Sandoz AG Crystalline dapagliflozin hydrate

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