CN102827153A - Crystal form of azilsartan and preparation method thereof - Google Patents
Crystal form of azilsartan and preparation method thereof Download PDFInfo
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- CN102827153A CN102827153A CN2011101586350A CN201110158635A CN102827153A CN 102827153 A CN102827153 A CN 102827153A CN 2011101586350 A CN2011101586350 A CN 2011101586350A CN 201110158635 A CN201110158635 A CN 201110158635A CN 102827153 A CN102827153 A CN 102827153A
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Abstract
The invention relates to a crystal form of azilsartan shown in formula (I) and a preparation method thereof, a pharmaceutical composition containing the crystal form, and an application of the crystal form or the pharmaceutical composition in preparing anti-hypertension medicaments.
Description
Technical field
The present invention relates to crystal formation of A Qishatan and preparation method thereof, comprise the pharmaceutical composition of this crystal formation, and this crystal formation or the purposes of its pharmaceutical composition in the preparation antihypertensive drug.
Background technology
A Qishatan (English name Azilsartan) is a kind of angiotensin ii receptor antagonist medicine that is in the treatment vascular hypertension in the research and development; Through of the vasoconstriction effect that combine block Angiotensin II of selective exclusion Angiotensin II with vascular smooth muscle AT1 acceptor; Be used to treat vascular hypertension, also be at present unique clinical angiotensin ii receptor antagonist in latter stage (husky smooth type) medicine that is in more.
In the 60th page of preparation method who discloses a kind of A Qishatan of patent CN1040755C specification sheets, wherein relate to the separation method of its crystal formation, after soon product distributes,, use re-crystallizing in ethyl acetate after the solvent evaporated again with the washing organic layer in water and chloroform.But A Qishatan is poorly soluble in ETHYLE ACETATE, and the crystal formation that utilizes this method to obtain yields poorly, purity difference, and stability is not good, is not suitable for the demand of industrial production and medicine preparation.
Summary of the invention
The object of the present invention is to provide a kind of being more suitable for, and a kind of productive rate and the higher crystal formation preparation method of purity are provided in the new crystal of pharmaceutical production requirement.
The object of the present invention is to provide the crystalline structure of A Qishatan shown in the formula I, the characteristic peak of described crystal form X ray powder diffraction pattern is positioned at 9.01 °, 12.60 °, 18.21 ° with 2 θ (± 0.2 ° of 2 θ) expression; Preferably, characteristic peak is positioned at 9.01 °, 12.60 °, 18.21 °, 19.21 °, 21.37 °, 23.42 °, 25.25 °, 26.58 °; More preferably, the characteristic peak of the crystal form X ray powder diffraction pattern of said A Qishatan is as shown in Figure 1,
Another purpose of the present invention is, a kind of method for preparing above-mentioned crystal formation is provided, and comprises the dissolving with A Qishatan, then with reaction solution reflux, crystallization at ambient temperature.
Preferably, A Qishatan is dissolved in the organic solvent, and more preferably, said organic solvent is an ethanol.
Another object of the present invention also is, a kind of pharmaceutical composition that contains the said A Qishatan crystal formation of treating significant quantity as effective constituent and pharmaceutically acceptable carrier is provided.
Another object of the present invention also is, said A Qishatan crystal formation or the said pharmaceutical composition purposes in the preparation antihypertensive drug is provided.
Crystalline structure stability provided by the present invention is better, and its physico-chemical property is more suitable for the demand of medicine preparation, and the productive rate and the purity of the product that the preparation method obtains of crystal formation of the present invention are higher, are suitable for suitability for industrialized production.
Description of drawings
Fig. 1 is the X-ray diffractogram of A Qishatan crystal formation.
Fig. 2 is 25 ℃ of A Qishatan, 400MHz's
1The HNMR collection of illustrative plates.
Fig. 3 is 25 ℃ of A Qishatan, 400MHz's
13The CNMR collection of illustrative plates.
Embodiment
With 2-oxyethyl group-1-([2 '-(2; 5-dihydro-5-oxygen-1,2,4-oxadiazole-3-yl) biphenyl-4-yl] methyl)-benzimidazolyl-7-carboxylate methyl ester (10g) is dissolved in methyl alcohol (727.3ml); The LiOH aqueous solution 62ml that adds 2N again; Reflux is 3 hours then, the solution pH value is transferred to 3, solvent evaporated with the hydrochloric acid of 2N.The gained resistates distributes in water (1.2L) and chloroform (3L); Wash organic layer and dry then, solvent evaporated joins products therefrom in the 220ml ethanol; Under the whipped state reaction solution is heated to backflow; After treating that solid dissolves fully, be cooled to the stirring at room crystallization, get off-white color solid 8g.
Can confirm that in conjunction with Fig. 2, Fig. 3 this white solid is A Qishatan.
In conjunction with the crystal form X x ray diffration pattern x of Fig. 1,, can find that crystal formation of the present invention is a kind of new crystal formation with the crystal formation collection of illustrative plates contrast of prior art.
Claims (9)
1. the crystalline structure of A Qishatan shown in the formula I,
2. crystalline structure as claimed in claim 1 is characterized in that, the characteristic peak of described crystal form X ray powder diffraction pattern is positioned at 9.01 °, 12.60 °, 18.21 ° with 2 θ (± 0.2 ° of 2 θ) expression.
3. crystalline structure as claimed in claim 2; It is characterized in that the characteristic peak of described crystal form X ray powder diffraction pattern is positioned at 9.01 °, 12.60 °, 18.21 °, 19.21 °, 21.37 °, 23.42 °, 25.25 °, 26.58 ° with 2 θ (± 0.2 ° of 2 θ) expression.
4. crystalline structure as claimed in claim 3 is characterized in that the characteristic peak of described crystal form X ray powder diffraction pattern is as shown in Figure 1.
5. a method for preparing like any described crystal formation of claim 1-4 comprises the dissolving with A Qishatan, at ambient temperature crystallization.
6. preparation method as claimed in claim 5 is characterized in that said A Qishatan is dissolved in the organic solvent.
7. preparation method as claimed in claim 6 is characterized in that said organic solvent is an ethanol.
8. contain the treatment significant quantity like the pharmaceutical composition of any described A Qishatan crystal formation of claim 1-4 as effective constituent and pharmaceutically acceptable carrier.
9. like any described A Qishatan crystal formation of claim 1-4 or the purposes of pharmaceutical composition as claimed in claim 8 in the preparation antihypertensive drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201110158635.0A CN102827153B (en) | 2011-06-14 | 2011-06-14 | Crystal formation of Azilsartan and preparation method thereof |
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| CN201110158635.0A CN102827153B (en) | 2011-06-14 | 2011-06-14 | Crystal formation of Azilsartan and preparation method thereof |
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| CN102827153A true CN102827153A (en) | 2012-12-19 |
| CN102827153B CN102827153B (en) | 2016-10-05 |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102766139A (en) * | 2012-08-14 | 2012-11-07 | 江苏先声药物研究有限公司 | Azilsartan polymorphic substance and preparation method thereof |
| CN103044412A (en) * | 2012-12-26 | 2013-04-17 | 华润赛科药业有限责任公司 | Azilsartan polymorph 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 |
| CN103664921A (en) * | 2013-11-27 | 2014-03-26 | 湖南千金湘江药业股份有限公司 | Azilsartan of crystal form A, and preparation method thereof |
| CN103930419A (en) * | 2011-09-30 | 2014-07-16 | 广东东阳光药业有限公司 | Crystalline forms of azilsartan and preparation and uses thereof |
| CN104262334A (en) * | 2014-09-16 | 2015-01-07 | 常州大学 | Azilsartan crystal 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 |
| CN104557899A (en) * | 2014-11-17 | 2015-04-29 | 江苏中邦制药有限公司 | Preparation method of azilsartan I-form 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 |
| CN110041320A (en) * | 2019-04-24 | 2019-07-23 | 浙江天宇药业股份有限公司 | A kind of preparation method of the crystallization of Azilsartan |
Citations (3)
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|---|---|---|---|---|
| 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 |
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2011
- 2011-06-14 CN CN201110158635.0A patent/CN102827153B/en active Active
Patent Citations (3)
| 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)
| Title |
|---|
| 束蓓艳，等: "阿奇沙坦的合成", 《中国医药工业杂志》, vol. 41, no. 12, 31 December 2010 (2010-12-31), pages 881 - 883 * |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103930419A (en) * | 2011-09-30 | 2014-07-16 | 广东东阳光药业有限公司 | Crystalline forms of azilsartan and preparation and uses thereof |
| US9174973B2 (en) | 2011-09-30 | 2015-11-03 | Sunshine Lake Pharma Co., Ltd. | Crystalline forms of azilsartan and preparation and uses thereof |
| CN102766139A (en) * | 2012-08-14 | 2012-11-07 | 江苏先声药物研究有限公司 | Azilsartan polymorphic substance and preparation method thereof |
| CN103044412A (en) * | 2012-12-26 | 2013-04-17 | 华润赛科药业有限责任公司 | Azilsartan polymorph 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 |
| CN103664921A (en) * | 2013-11-27 | 2014-03-26 | 湖南千金湘江药业股份有限公司 | Azilsartan of crystal form A, 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 |
| CN104557899A (en) * | 2014-11-17 | 2015-04-29 | 江苏中邦制药有限公司 | Preparation method of azilsartan I-form crystal |
| 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 |
| CN110041320A (en) * | 2019-04-24 | 2019-07-23 | 浙江天宇药业股份有限公司 | A kind of preparation method of the crystallization of Azilsartan |
| 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 |
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| CN102827153B (en) | 2016-10-05 |
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Address after: Tenth Industrial Zone, Lianyungang, Jiangsu, China, 222047 Applicant after: JIANGSU HANSOH PHARMACEUTICAL Co.,Ltd. Applicant after: Lianyungang Hongchuang Pharmaceutical Co.,Ltd. Address before: Tenth Industrial Zone, Lianyungang, Jiangsu, China, 222047 Applicant before: JIANGSU HANSOH PHARMACEUTICAL Co.,Ltd. Applicant before: JIANGSU HANSOH PHARMACEUTICAL GROUP LIANYUNGANG HONGCHUANG PHARMACEUTICAL Co.,Ltd. |
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Address after: Tenth Industrial Zone, Lianyungang, Jiangsu, China, 222047 Applicant after: Jiangsu best Pharmaceutical Co.,Ltd. Applicant after: Lianyungang Hongchuang Pharmaceutical Co.,Ltd. Address before: Tenth Industrial Zone, Lianyungang, Jiangsu, China, 222047 Applicant before: JIANGSU HANSOH PHARMACEUTICAL Co.,Ltd. Applicant before: Lianyungang Hongchuang Pharmaceutical Co.,Ltd. Address after: Tenth Industrial Zone, Lianyungang, Jiangsu, China, 222047 Applicant after: JIANGSU HANSOH PHARMACEUTICAL GROUP Co.,Ltd. Applicant after: Lianyungang Hongchuang Pharmaceutical Co.,Ltd. Address before: Tenth Industrial Zone, Lianyungang, Jiangsu, China, 222047 Applicant before: Jiangsu best Pharmaceutical Co.,Ltd. Applicant before: Lianyungang Hongchuang Pharmaceutical Co.,Ltd. |
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Effective date of registration: 20160318 Address after: Tenth Industrial Zone, Lianyungang, Jiangsu, China, 222047 Applicant after: JIANGSU HANSOH PHARMACEUTICAL GROUP Co.,Ltd. Address before: Tenth Industrial Zone, Lianyungang, Jiangsu, China, 222047 Applicant before: JIANGSU HANSOH PHARMACEUTICAL GROUP Co.,Ltd. Applicant before: Lianyungang Hongchuang Pharmaceutical Co.,Ltd. |
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Application publication date: 20121219 Assignee: JIANGXI SYNERGY PHARMACEUTICAL CO.,LTD. Assignor: JIANGSU HANSOH PHARMACEUTICAL GROUP Co.,Ltd. Contract record no.: X2023980034034 Denomination of invention: The crystal form of azilsartan and its preparation method Granted publication date: 20161005 License type: Common License Record date: 20230324 |