CN101805289A - Omega-crystal form, preparation method and medicine composite of ivabradine hydrochloride - Google Patents
Omega-crystal form, preparation method and medicine composite of ivabradine hydrochloride Download PDFInfo
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- CN101805289A CN101805289A CN200910058345A CN200910058345A CN101805289A CN 101805289 A CN101805289 A CN 101805289A CN 200910058345 A CN200910058345 A CN 200910058345A CN 200910058345 A CN200910058345 A CN 200910058345A CN 101805289 A CN101805289 A CN 101805289A
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- ivabradine hydrochloride
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Abstract
The invention discloses a new crystal form omega-crystal form of ivabradine hydrochloride and preparation method thereof. The mixture of the ivabradine hydrochloride and water is heated and dissolved completely and then is frozen and dried to obtain delta-crystal form crystal. The crystal form has stable temperature and humidity, does not contain any organic solvent and moisture and is applicable to preparation technical process and a long period of storage. The medicine composite taking the crystal form composite as active ingredient can be used to treat or prevent angina, myocardial infarction and relative arhythmicity.
Description
Technical field
The present invention relates to the ω-crystal formation, its preparation method of Ivabradine hydrochloride and be the pharmaceutical composition of activeconstituents with this compound.
Background technology
Its chemistry of S 16257-2 3-{3-[{[(7S by name)-3,4-dimethoxy dicyclo [4.2.0] hot-1,3,5-triolefin-7-yl]-methyl } (methyl)-amino] propyl group }-7,8-dimethoxy-1,3,4,5-tetrahydrochysene-2H-3-phenylpropyl alcohol azatropylidene-2-ketone, the general formula (I) of Ivabradine hydrochloride (Ivabradine hydrochloride) is:
Ivabradine hydrochloride has very valuable pharmacological and treatment characteristic, especially decreasing heart rate (bradycardic) characteristic, thereby make this compound can be used for treating or preventing various clinical settings such as stenocardia, myocardial infarction and the relevant arhythmicity of scarce of cardiac muscle, and relate to the various case situations of arhythmicity, especially supraventricular arhythmicity and heart failure.
The preparation and the therepic use of additive salt, the especially hydrochloride of having described S 16257-2 among the European patent specification EP0534859 and having formed with pharmaceutically acceptable acid.
Described the method for synthesis of ivabradine and hydrochloride thereof among the patent specification EP0534859, but but given the special condition that is used for showing the S 16257-2 formation of those features that describes in detail in the document with the playback system acquisition.
Chinese patent CN1683341, CN1827599, CN1827600, CN1827601, CN1827602, CN1948292, CN1948293 have put down in writing the multiple crystal formation that relates to this compound of Servier Lab's invention such as α, β, β
d, γ, γ
d, δ, δ
dAnd the preparation method, Chinese patent CN101353325 has put down in writing the stable crystal formation that relates to this compound and each method of system of Shanghai UTopharm Co., Ltd.'s invention.
Summary of the invention
The object of the present invention is to provide the new crystal formation of a kind of this compound, this crystal formation is different from aforesaid any, and it has good temperature, humidity stability, and does not contain any organic solvent and moisture, is fit to preparation technical process and standing storage.
Another object of the present invention be to provide the new crystal formation of a kind of this compound the preparation method.
It is the pharmaceutical composition of activeconstituents with this compound that further purpose of the present invention is to provide a kind of, can be used for treating or preventing the medicine of stenocardia, myocardial infarction and relevant arhythmicity.
The present invention relates to the ω-crystal formation of Ivabradine hydrochloride, it is characterized in that following powder X-ray ray shoots figure, use instrument PANalytical X ' Pert Pro diffractometer and X ' Celerator detector and detect acquisition, with position of spectral line (Bragg ' s 2 θ angles, show), height of spectral line (with the counting expression), relative abundance (representing) and spacing d with per-cent with kilsyth basalt (with
Expression) expression:
The preparation method of the ω-crystal formation of Ivabradine hydrochloride of the present invention, its method are that the mixture heating up of Ivabradine hydrochloride and water is dissolved fully, and lyophilize obtains crystal then.
In the method for the invention, may use the Ivabradine hydrochloride that obtains by any means, for example the Ivabradine hydrochloride that obtains by the preparation method described in the European patent EP 0534859.
The invention still further relates to pharmaceutical composition, comprise ω-crystal formation and one or more pharmaceutically acceptable inert non-toxic carriers as the Ivabradine hydrochloride of activeconstituents, in the pharmaceutical composition in the present invention, what more specifically can mention is to be suitable for those of oral, parenteral (intravenously or subcutaneous) or nasal administration, tablet or drageeing, Sublingual tablet, gelatine capsule, tincture, suppository, creme, ointment, skin gel, injectable formulation, drinkable suspensoid.
Useful dosage can change according to the character of disease and severity, route of administration and patient's age and body weight.This dosage changed between 1-500mg/ days, in single or divided doses.
Description of drawings
Fig. 1 is the x-ray diffractogram of powder of the ω-crystal formation of Ivabradine hydrochloride.
Embodiment
Embodiment 1: the ω-crystal formation of Ivabradine hydrochloride
To be added in the 30ml purified water according to the 20 gram Ivabradine hydrochlorides that the described method of European patent specification EP0534859 obtains, heating is stirred simultaneously, until dissolving fully.Cooling then, lyophilize.Demonstration has generated ω-crystal formation according to XRD.
Embodiment 2: pharmaceutical composition
Prepare 1000 prescriptions that contain the tablet of 7.5mg Febuxostat separately:
The compound 8.085g of embodiment 1
W-Gum 30g
Mannitol 85g
PVP 11.5g
Magnesium Stearate 0.8g.
Claims (4)
1. the Ivabradine hydrochloride of general formula (I):
It is characterized in that ω-crystal formation that crystal formation is.
2. according to the described compound of claim 1, it is characterized in that this crystalline X ray powder diffractogram is 6.69,8.09,9,12 at reflection angle 2 θ, 9,68,9.95,12.13,13.19,14.25,14.78,15.65,16.80,18.17,18.37,18.74,19.59,20.43,20.77,21.18,21.47,22.53,23.10,23.71,25.30,26.13,26.60,27.37,27.76,28.06,28.78,29.20,30.25,31.21,32.04,32.50,33.26,33.84,34.31,34.98,36.20,36.80,37.86,39.60,40.71,41.39,43.01,44.44,46.00,47.06,48.13.
3. the preparation method of the crystal formation of the compound of claim 1 is characterized in that the mixture heating up of Ivabradine hydrochloride and water is dissolved fully, and lyophilize obtains ω-crystal formation crystal then.
4. be used for the treatment of or prevent the pharmaceutical composition of stenocardia, myocardial infarction and relevant arhythmicity, it is characterized in that, wherein contain compound and one or more pharmaceutically acceptable inert non-toxic carriers of the claim 1 for the treatment of significant quantity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910058345A CN101805289A (en) | 2009-02-17 | 2009-02-17 | Omega-crystal form, preparation method and medicine composite of ivabradine hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910058345A CN101805289A (en) | 2009-02-17 | 2009-02-17 | Omega-crystal form, preparation method and medicine composite of ivabradine hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101805289A true CN101805289A (en) | 2010-08-18 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN200910058345A Pending CN101805289A (en) | 2009-02-17 | 2009-02-17 | Omega-crystal form, preparation method and medicine composite of ivabradine hydrochloride |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102304088A (en) * | 2011-07-07 | 2012-01-04 | 石药集团欧意药业有限公司 | Ivabradine compound, preparation method and pharmaceutical composition thereof |
| WO2012025940A1 (en) * | 2010-08-25 | 2012-03-01 | Cadila Healthcare Limited | Polymorphic form of ivabradine hydrochloride and process for preparation thereof |
| EP2589594A1 (en) | 2011-11-04 | 2013-05-08 | Urquima S.A. | Ivabradine hydrochloride Form IV |
| WO2013102919A1 (en) * | 2011-11-14 | 2013-07-11 | Cadila Healthcare Limited | Polymorphic forms of ivabradine hydrochloride |
| WO2015101072A1 (en) * | 2014-01-06 | 2015-07-09 | 北京莱瑞森医药科技有限公司 | S crystal form of ivabradine hydrochloride, and preparation method and pharmaceutical composition thereof |
| WO2020088480A1 (en) * | 2018-10-30 | 2020-05-07 | 中国科学院化学研究所 | Method for preparing single crystal or amorphous substance via solution freezing |
-
2009
- 2009-02-17 CN CN200910058345A patent/CN101805289A/en active Pending
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012025940A1 (en) * | 2010-08-25 | 2012-03-01 | Cadila Healthcare Limited | Polymorphic form of ivabradine hydrochloride and process for preparation thereof |
| CN102304088B (en) * | 2011-07-07 | 2013-06-19 | 石药集团欧意药业有限公司 | Ivabradine compound, preparation method and pharmaceutical composition thereof |
| CN102304088A (en) * | 2011-07-07 | 2012-01-04 | 石药集团欧意药业有限公司 | Ivabradine compound, preparation method and pharmaceutical composition thereof |
| JP2017178965A (en) * | 2011-11-04 | 2017-10-05 | ウルキマ，ソシエダッド アノニマ | Ivabradine hydrochloride form iv |
| US9309201B2 (en) | 2011-11-04 | 2016-04-12 | Urquima, S.A. | Process for preparating ivabradine hydrochloride form IV and methods of treatment of disease using ivabradine hydrochloride form IV |
| EP3263556A1 (en) | 2011-11-04 | 2018-01-03 | Urquima, S.A. | Ivabradine hydrochloride form iv |
| JP2014532673A (en) * | 2011-11-04 | 2014-12-08 | ウルキマ，ソシエダッド アノニマ | Ivabradine hydrochloride Form IV |
| EP2589594A1 (en) | 2011-11-04 | 2013-05-08 | Urquima S.A. | Ivabradine hydrochloride Form IV |
| WO2013064307A1 (en) | 2011-11-04 | 2013-05-10 | Urquima, S. A. | Ivabradine hydrochloride form iv |
| US9139531B2 (en) | 2011-11-04 | 2015-09-22 | Urquima, S.A. | Ivabradine hydrochloride form IV |
| EP3156399A1 (en) * | 2011-11-14 | 2017-04-19 | Cadila Healthcare Limited | Polymorphic forms of ivabradine hydrochloride |
| US9382209B2 (en) | 2011-11-14 | 2016-07-05 | Cadila Healthcare Limited | Polymorphic forms of ivabradine hydrochloride |
| US9120755B2 (en) | 2011-11-14 | 2015-09-01 | Cadila Healthcare Limited | Polymorphic forms of ivabradine hydrochloride |
| US9650344B2 (en) | 2011-11-14 | 2017-05-16 | Cadila Healthcare Limited | Polymorphic forms of ivabradine hydrochloride |
| US9840469B2 (en) | 2011-11-14 | 2017-12-12 | Cadila Healthcare Limited | Polymorphic forms of ivabradine hydrochloride |
| WO2013102919A1 (en) * | 2011-11-14 | 2013-07-11 | Cadila Healthcare Limited | Polymorphic forms of ivabradine hydrochloride |
| US9676725B2 (en) | 2014-01-06 | 2017-06-13 | Beijing Lunarsun Pharmaceutical Co., Ltd. | S-crystal form of ivabradine hydrochloride, and preparation method and pharmaceutical composition thereof |
| WO2015101072A1 (en) * | 2014-01-06 | 2015-07-09 | 北京莱瑞森医药科技有限公司 | S crystal form of ivabradine hydrochloride, and preparation method and pharmaceutical composition thereof |
| RU2658824C2 (en) * | 2014-01-06 | 2018-06-25 | Бейджинг Лунарсан Фармасьютикал Ко., Лтд. | S-crystal form of ivabradine hydrochloride, preparation method and pharmaceutical composition thereof |
| WO2020088480A1 (en) * | 2018-10-30 | 2020-05-07 | 中国科学院化学研究所 | Method for preparing single crystal or amorphous substance via solution freezing |
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Application publication date: 20100818 |