CN102827153B - Crystal formation of Azilsartan and preparation method thereof - Google Patents

Crystal formation of Azilsartan and preparation method thereof Download PDF

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Publication number
CN102827153B
CN102827153B CN201110158635.0A CN201110158635A CN102827153B CN 102827153 B CN102827153 B CN 102827153B CN 201110158635 A CN201110158635 A CN 201110158635A CN 102827153 B CN102827153 B CN 102827153B
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crystal formation
azilsartan
crystal
compound
medicine
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CN102827153A (en
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潘必高
杨宝海
黄龙彬
吕爱锋
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Jiangsu Hansoh Pharmaceuticals Co Ltd
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Jiangsu Hansoh Pharmaceuticals Co Ltd
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Abstract

The present invention relates to crystal formation of Azilsartan shown in formula (I) and preparation method thereof, and comprise the pharmaceutical composition of this crystal formation, and this crystal formation or pharmaceutical composition are for preparing the application in drug for hypertension.

Description

Crystal formation of Azilsartan and preparation method thereof
Technical field
Crystal formation that the present invention relates to Azilsartan and preparation method thereof, comprises the medicine group of this crystal formation Compound, and this crystal formation or purposes in preparing drug for hypertension for its pharmaceutical composition.
Background technology
Azilsartan (English name Azilsartan) is that a kind for the treatment of being in research and development is high The angiotensin II receptor antagonist medicine of blood pressure disease, by selective exclusion vasotonia The combination of element II and vascular smooth muscle AT1 acceptor and the vasoconstriction that blocks Angiotensin II Effect, is used for treating vascular hypertension, is also the currently the only vasotonia being in late-stage clinical Element II receptor antagonist (husky smooth class) medicine.
Disclose the preparation of a kind of Azilsartan in patent CN1040755C specification page 60 Method, is directed to the separation method of its crystal formation, will after product distributes in water and chloroform, Wash organic layer with water, after solvent evaporated, use re-crystallizing in ethyl acetate again.But, Azilsartan exists Dissolubility difference in ethyl acetate, the crystal formation utilizing the method to obtain yields poorly, purity difference, stable Property is not good, is not suitable for the demand of industrial production and medicine preparation.
Content of the invention
It is an object of the invention to provide a kind of novel crystal forms being more suitable for pharmaceutical production requirement, and A kind of productivity and purity higher crystal formation preparation method are provided.
It is an object of the invention to provide the crystalline structure of Azilsartan shown in formula (I), described The characteristic peak of crystal formation X-ray powder diffraction figure represent with 2 θ (± 0.2 ° of 2 θ) be positioned at 9.01 °, 12.60°、18.21°;Preferably, characteristic peak be positioned at 9.01 °, 12.60 °, 18.21 °, 19.21 °, 21.37°、23.42°、25.25°、26.58°;It is highly preferred that the crystal formation X of described Azilsartan The characteristic peak of ray powder diffraction pattern as it is shown in figure 1,
It is a further object of the present invention to provide a kind of method preparing above-mentioned crystal formation, including Azilsartan is dissolved, then reactant liquor is heated to reflux, at ambient temperature crystallization.
Preferably, Azilsartan dissolves in organic solvent, it is further preferred that described organic molten Agent is ethanol.
Another object of the present invention also resides in, and provides a kind of described A Qi containing therapeutically effective amount Husky smooth crystal formation is as the pharmaceutical composition of active ingredient and pharmaceutically acceptable carrier.
Another object of the present invention also resides in, and provides described Azilsartan crystal formation or described medicine group Purposes in preparing drug for hypertension for the compound.
Crystalline structure stability provided by the present invention is more preferable, and its physico-chemical property is more suitable for medicine system The demand of agent, and productivity and the purity of the obtained product of preparation method of crystal formation of the present invention are higher, Be suitable to industrialized production.
Brief description
Fig. 1 is the X-ray diffractogram of Azilsartan crystal formation.
Fig. 2 is Azilsartan 25 DEG C, 400MHz's1HNMR collection of illustrative plates.
Fig. 3 is Azilsartan 25 DEG C, 400MHz's13CNMR collection of illustrative plates.
Detailed description of the invention
By 2-ethyoxyl-1-([2 '-(2,5-dihydro-5-oxygen-1,2,4-diazole-3-bases) biphenyl-4-base] Methyl)-benzimidazole-7-carboxylate methyl ester (10g) is dissolved in methyl alcohol (727.3ml), then adds 2N's LiOH aqueous solution 62ml, is then heated to reflux 3 hours, with the hydrochloric acid of 2N by solution PH Value is adjusted to 3, solvent evaporated.Gained residue is carried out in water (1.2L) and chloroform (3L) Distribution, then washes organic layer and is dried, solvent evaporated, products therefrom is joined 220ml In ethanol, under stirring, reactant liquor is heated to backflow, after solid is completely dissolved, cooling To crystallization is stirred at room temperature, obtain off-white color solid 8g.
May determine that this white solid is Azilsartan in conjunction with Fig. 2, Fig. 3.
In conjunction with the crystal formation X-ray diffractogram of Fig. 1, contrast with the crystal formation collection of illustrative plates of prior art, It appeared that the crystal formation of the present invention is a kind of new crystal formation.

Claims (4)

1. the crystalline structure of formula (I) compound,
It is characterized in that, the characteristic peak such as accompanying drawing 1 of described crystal formation X-ray powder diffraction figure Shown in.
2. the method preparing crystal formation as claimed in claim 1, including by Azilsartan Dissolve, crystallization at ambient temperature, it is characterised in that described Azilsartan is dissolved in organic molten In agent, described organic solvent is ethanol.
3. contain the compound crystal form as claimed in claim 1 of therapeutically effective amount as effectively Composition and the pharmaceutical composition of pharmaceutically acceptable carrier.
4. compound crystal form as claimed in claim 1 or medicine as claimed in claim 3 Purposes in preparing drug for hypertension for the composition.
CN201110158635.0A 2011-06-14 2011-06-14 Crystal formation of Azilsartan and preparation method thereof Active CN102827153B (en)

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Application Number Priority Date Filing Date Title
CN201110158635.0A CN102827153B (en) 2011-06-14 2011-06-14 Crystal formation of Azilsartan and preparation method thereof

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CN102827153B true CN102827153B (en) 2016-10-05

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Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013044816A1 (en) * 2011-09-30 2013-04-04 Sunshine Lake Pharma Co., Ltd. Crystalline forms of azilsartan and preparation and uses thereof
CN102766139B (en) * 2012-08-14 2014-09-17 江苏先声药物研究有限公司 Azilsartan polymorphic substance and preparation method thereof
CN103044412B (en) * 2012-12-26 2016-04-06 华润赛科药业有限责任公司 Polymorphic of a kind of Azilsartan and preparation method thereof
CN103319473A (en) * 2013-07-02 2013-09-25 合肥医工医药有限公司 Two crystal forms of azilsartan and preparation method thereof
CN104341408A (en) * 2013-08-02 2015-02-11 江苏柯菲平医药股份有限公司 Novel crystal form of azilsartan and preparation method thereof
CN103664921B (en) * 2013-11-27 2016-08-24 湖南千金湘江药业股份有限公司 A kind of Azilsartan crystal formation A and preparation method thereof
CN104262334A (en) * 2014-09-16 2015-01-07 常州大学 Azilsartan crystal and preparation method thereof
CN104557899B (en) * 2014-11-17 2018-05-22 江苏中邦制药有限公司 A kind of preparation method of Azilsartan I crystal crystal
CN106749217A (en) * 2017-01-22 2017-05-31 鲁南制药集团股份有限公司 A kind of Azilsartan I crystal
CN110041320B (en) * 2019-04-24 2020-11-20 浙江天宇药业股份有限公司 Preparation method of azilsartan crystals

Citations (3)

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Publication number Priority date Publication date Assignee Title
CN1067890A (en) * 1991-06-27 1993-01-13 武田药品工业株式会社 Heterogeneous ring compound, its preparation and application
WO2006107062A2 (en) * 2005-03-30 2006-10-12 Takeda Pharmaceutical Company Limited Benzimidazole derivative and use as angiotensin ii antagonist
US7157584B2 (en) * 2004-02-25 2007-01-02 Takeda Pharmaceutical Company Limited Benzimidazole derivative and use thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1067890A (en) * 1991-06-27 1993-01-13 武田药品工业株式会社 Heterogeneous ring compound, its preparation and application
US7157584B2 (en) * 2004-02-25 2007-01-02 Takeda Pharmaceutical Company Limited Benzimidazole derivative and use thereof
WO2006107062A2 (en) * 2005-03-30 2006-10-12 Takeda Pharmaceutical Company Limited Benzimidazole derivative and use as angiotensin ii antagonist

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
阿奇沙坦的合成;束蓓艳,等;《中国医药工业杂志》;20101231;第41卷(第12期);第881-883页 *

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