CN101805310A - 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazolyl formic acid of delta-crystal form, as well as preparation method and medicine composite thereof - Google Patents
2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazolyl formic acid of delta-crystal form, as well as preparation method and medicine composite thereof Download PDFInfo
- Publication number
- CN101805310A CN101805310A CN200910058344A CN200910058344A CN101805310A CN 101805310 A CN101805310 A CN 101805310A CN 200910058344 A CN200910058344 A CN 200910058344A CN 200910058344 A CN200910058344 A CN 200910058344A CN 101805310 A CN101805310 A CN 101805310A
- Authority
- CN
- China
- Prior art keywords
- preparation
- crystal form
- compound
- methyl
- crystal formation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The invention discloses 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazolyl formic acid of a new delta-crystal form and a preparation method thereof. The method comprises the steps of: heating a mixture of Febuxostat and absolute ethanol till completely dissolving, and then filtering to obtain an alcoholate; putting the alcoholate in a 80 DEG C baking oven for baking for 2 hours under 2mmHg vacuum decompression to obtain crystals of the delta-crystal form, which has excellent temperature and humidity stability, no any organic solvents or water and is suitable for preparation process and long-term storage. A medicine composite which takes the compound of the crystal form can be used for reducing uric acid in blood and treating all clinical hyperlithic situations, such as uarthritis.
Description
Technical field
The present invention relates to the δ-crystal formation, its preparation method of 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazole formic acid and be the pharmaceutical composition of activeconstituents with this compound.
Background technology
2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazole formic acid is commonly called as Febuxostat (Febuxostat), and structural formula (I) is:
Febuxostat has very valuable pharmacological and treatment characteristic, especially suppresses the activity of XOD, thereby makes this compound can be used for treatment and hyperlithic disease, as gout, is used for reducing the uric acid of blood.
The preparation and the therepic use of Febuxostat have been described among the international patent specification WO92/09279.But not mentioned compound crystal formation phenomenon, so the crystal formation situation of this compound is unclear.From the experimental implementation of wherein describing, can be speculated as ethylate, and the form of ethylate has been brought very big restriction to its conduct application pharmaceutically.
What Chinese patent CN1275126 had put down in writing the invention of Supreme Being people company relates to multiple crystal form A, B, C, D, G and indefiniteness of this compound and preparation method thereof, and Chinese patent CN1970547 has put down in writing multiple crystal formation H, I, J and preparation method thereof of relating to this compound of Chongqing Medicine Industry Academe 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 as the uric acid that reduces in the blood, treats hyperlithic various clinical setting such as gout.
More specifically, the present invention relates to the δ-crystal formation of Febuxostat, it is characterized in that following x-ray diffractogram of powder, use instrument: PANalytical X ' Pert Pro diffractometer and X ' Celerator detector detect and obtain, 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 δ-crystal formation of Febuxostat of the present invention, its method is filtered then and is obtained ethylate for the mixture heating up of Febuxostat and dehydrated alcohol is dissolved fully, and this ethylate places 80 ℃ of baking ovens, the 2mmHg vacuum decompression toasted 2 hours down, obtained δ-crystal formation xln.
Febuxostat can pass through the Febuxostat that the preparation method described in the international monopoly WO92/09279 obtains in the method for the invention.
Pharmaceutical composition of the present invention, comprise δ-crystal formation and one or more pharmaceutically acceptable inert non-toxic carriers as the Febuxostat of activeconstituents, in the pharmaceutical composition in the present invention, what more specifically can mention is to be suitable for oral, injection and external preparation, oral preparations can be tablet, capsule, particle, control slow releasing tablet or capsule, intraoral disintegration, dissolving and dispersive tablet.
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 2-(x-ray diffractogram of powder of the δ-crystal formation of 3-cyano-4-isobutoxy phenyl-4-methyl-5-thiazole formic acid (Febuxostat).
Embodiment
Embodiment 1: the δ-crystal formation of Febuxostat preparation
To be added in the 200ml dehydrated alcohol according to the 20 gram Febuxostats that the described method of international patent specification WO92/0927920 obtains, reflux stirs simultaneously, until dissolving fully.The settled solution of gained was refluxed 1 hour again, and cooling is then filtered.The solid of gained is placed 80 ℃ of baking ovens, 2mmHg vacuum decompression dry 2 hours down.Demonstration has generated δ-crystal formation according to XRD.
Embodiment 2: pharmaceutical composition
Prepare 1000 prescriptions that contain the tablet of 120mg Febuxostat separately:
The compound 120g of embodiment 1
Pregelatinized Starch 110g
PVP 11.5g
Magnesium Stearate 0.8g
Claims (4)
1.2-(3-cyano group-
The base phenyl)-and the 4-methyl-5-thiazole formic acid, structural formula (I) is:
It is characterized in that crystal formation is δ-crystal formation.
2. according to the described compound of claim 1, it is characterized in that this crystalline X ray powder diffractogram is 6.76,7.17,8.13,9.51 at reflection angle 2 θ, 11.51,12.79,17.07,19.12,19.80,21.76,23.51,23.83,24.36,25.17,25.94,26.76,28.31,29.23,30.12,31.24,33.48,34.44,35.31,36.23,37.25,38.89,40.58,44.90,46.22,47.30,48.23,49.07.
3. the preparation method of the crystal formation of the compound of claim 1, it is characterized in that the mixture heating up of compound and dehydrated alcohol is dissolved fully, filter then and obtain ethylate, this ethylate places 80 ℃ of baking ovens, the 2mmHg vacuum decompression toasted 2 hours down, obtained xln.
4. be used for the treatment of hyperlithic pharmaceutical composition, 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 |
|---|---|---|---|
| CN200910058344A CN101805310A (en) | 2009-02-17 | 2009-02-17 | 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazolyl formic acid of delta-crystal form, as well as preparation method and medicine composite thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910058344A CN101805310A (en) | 2009-02-17 | 2009-02-17 | 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazolyl formic acid of delta-crystal form, as well as preparation method and medicine composite thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101805310A true CN101805310A (en) | 2010-08-18 |
Family
ID=42607279
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910058344A Pending CN101805310A (en) | 2009-02-17 | 2009-02-17 | 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazolyl formic acid of delta-crystal form, as well as preparation method and medicine composite thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101805310A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8415481B2 (en) | 2009-06-10 | 2013-04-09 | Teva Pharmaceuticals Usa, Inc. | Crystalline form of febuxostat |
| CN103396378A (en) * | 2013-07-29 | 2013-11-20 | 杭州朱养心药业有限公司 | Stable febuxostat crystal |
| WO2016091230A1 (en) | 2014-12-12 | 2016-06-16 | Zentiva, K.S. | Formulations containing a solid solution of febuxostat |
-
2009
- 2009-02-17 CN CN200910058344A patent/CN101805310A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8415481B2 (en) | 2009-06-10 | 2013-04-09 | Teva Pharmaceuticals Usa, Inc. | Crystalline form of febuxostat |
| US8609856B2 (en) | 2009-06-10 | 2013-12-17 | Teva Pharmaceuticals Usa, Inc. | Crystalline forms of Febuxostat |
| US8742129B2 (en) | 2009-06-10 | 2014-06-03 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of febuxostat |
| CN103396378A (en) * | 2013-07-29 | 2013-11-20 | 杭州朱养心药业有限公司 | Stable febuxostat crystal |
| CN103396378B (en) * | 2013-07-29 | 2015-06-10 | 杭州朱养心药业有限公司 | Stable febuxostat crystal |
| WO2016091230A1 (en) | 2014-12-12 | 2016-06-16 | Zentiva, K.S. | Formulations containing a solid solution of febuxostat |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1910154B (en) | Quinoline derivatives for use as mycobacterial inhibitors | |
| EP3594214A1 (en) | Polymorph of compound, preparation method therefor and use thereof | |
| JP2009506014A5 (en) | ||
| US6858644B2 (en) | Paclitaxel solvates | |
| CN1970547B (en) | Novel febuxostat crystal form and its preparation method | |
| CN101203211B (en) | Pharmaceutical composition | |
| CN101955440B (en) | Crystal form of agomelatine and preparation method thereof | |
| JP2011068653A5 (en) | ||
| JP2004256555A (en) | Aripiprazole anhydride crystal, method for producing the same and medicinal preparation containing the same | |
| KR20070050967A (en) | 4-[[(7R) -8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-4-6-oxo-2-pteridinyl] amino] -3-meth Hydrates and polymorphs of oxy-N- (1-methyl-4-piperidinyl) benzamide, methods for their preparation, and their use as medicaments | |
| CA2597632A1 (en) | Substituted sulfoxide compounds, methods for preparing the same and use thereof | |
| CN107840830A (en) | Ozamod Hydrochloride Anhydrous Form I | |
| CN104744445A (en) | Crystal form of tyrosine kinase inhibitor | |
| CN101805310A (en) | 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazolyl formic acid of delta-crystal form, as well as preparation method and medicine composite thereof | |
| JP2009143954A (en) | Thiazolidinedione derivative and its use as antidiabetic drug | |
| CN101805289A (en) | Omega-crystal form, preparation method and medicine composite of ivabradine hydrochloride | |
| CN103360298A (en) | Preparation method of beta type silodosin crystal | |
| WO2014056396A1 (en) | Flumatinib mesylate crystal form and preparation method and use thereof | |
| WO2011140858A1 (en) | Aildenafil citrate crystal form o, preparation method and use thereof | |
| EP4025208A1 (en) | Cannabigerol proline cocrystals | |
| CN104496994B (en) | A kind of novel crystal forms of acetylenic heteroaryl compounds | |
| CN110483478B (en) | A kind of crystalline trelagliptin, preparation method and application thereof, trelagliptin succinate crystal and preparation method thereof | |
| CN107129502A (en) | EOC315 Mod.I crystal compound and preparation method thereof | |
| CN1913897A (en) | Novel compound, corresponding compositions, preparation and/or treatment methods | |
| CN105106221B (en) | A kind of medical application of genistein chromic compound in treatment diabetes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20100818 |