CN107304190A - A kind of preparation method of crystalline form of Valsartan - Google Patents
A kind of preparation method of crystalline form of Valsartan Download PDFInfo
- Publication number
- CN107304190A CN107304190A CN201610250332.4A CN201610250332A CN107304190A CN 107304190 A CN107304190 A CN 107304190A CN 201610250332 A CN201610250332 A CN 201610250332A CN 107304190 A CN107304190 A CN 107304190A
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- Prior art keywords
- valsartan
- crystal formations
- crystal
- preparation
- solvent
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to field of pharmaceutical chemistry technology.Disclose crystalline form of Valsartan F and preparation method thereof, it is found that new crystal formation has more excellent physical chemistry and patent medicine performance.Novel valsartan crystal form preparation method of the present invention is simple, is easily controlled, favorable reproducibility, can stablize and obtain target crystal formation.
Description
Technical field
It is related to a kind of preparation method of crystalline form of Valsartan the invention belongs to field of pharmaceutical chemistry technology.
Technical background
In drug research field, polymorphic includes the multicomponent crystal form such as organic solvate, hydrate.Medicine polymorphism is in drug development
During be widely present, be the intrinsic characteristic of organic micromolecule compound.Small-molecule drug can have infinite number of crystal accumulation mode-many in theory
Crystal formation, research shows, the time for the research that discovery quantity and its of polymorph in pharmaceuticals are put into and resource are in direct ratio；Will using DSC, TGA,
DVS, HPLC etc. carry out physical and chemical performance research to crystal formation, compare the hygroscopicity of different crystal forms, chemically stable, physical state stability, can process
Property etc. is studied.Highly preferred solid forms are finally selected to develop；Different crystal forms have different colors, fusing point, dissolving, stripping property
Energy, chemical stability, reactivity, mechanical stability etc., these physical and chemical performances or processability directly influence sometimes medicine safety,
Effective performance.Therefore crystal formation research and control turn into the important research content in drug development process.
Valsartan (Valsartan) it is chemical entitled：(S)-N- (1- valeryls)-N- [[2 '-(1H-TETRAZOLE -5- bases) [1,1 '-biphenyl] -4- bases] first
Base]-Valine, its chemical structural formula is as follows：
The content of the invention
Valsartan is a kind of small-molecule drug with specific blood vessels angiotensin II antagonistic agent activity for acting on AT1 receptor subtypes, is faced at present
Treatment hypertension is widely used on bed.Valsartan has polymorphism, it was reported that have amorphous and 20 kinds of crystal formations so far.
The present invention is intended to provide stable novel valsartan crystal form figured silk fabrics ethanolates F crystalline structure formulas are as follows：
The preparation method of the ethanolates F crystal formations of Valsartan, comprises the following steps：
(1) it is suspended：Under room temperature to solvent boiling point temperature conditionss, the mass volume ratio by Valsartan and solvent suspension wherein Valsartan and solvent is
(gram/L) 10: 1-100: 1
(2) stir：Above-mentioned suspension is stirred with magnetic stir bar, rotating speed is 60-550rpm, mixing time is 3-6 days
(3) dry：Above-mentioned suspension is filtered, after being washed with a small amount of solvent used that is suspended, figured silk fabrics is produced in room temperature to 100 DEG C of decompression dryings
Sha Tan ethanolates F crystal formations crystallization；
Wherein, the solvent is the organic solvents such as methanol or ethanol and methanol, acetone, acetonitrile, ether, tetrahydrofuran, n-hexane, normal heptane
Or the mixture of water formation
Novel crystal forms crystallinity is high, hygroscopicity is small, and forms regular crystal kenel, is conducive to the PROCESS FOR TREATMENT of medicine and the improvement of physical and chemical performance, carries
High patent medicine performance
Embodiment 1
10.0g Valsartans are placed in conical flask, suspension is mixed to form with ethanol/water (volume ratio 2: 1) mixed solvent 150mL.Add
Magnetic stir bar is stirred, and rotating speed is 150rpm, keeps stirring 2 days at ambient temperature.Suspension is filtered, with a small amount of ethanol/water (body
Product ratio 2: 1) after mixed solvent washing, in reduced pressure at room temperature.White crystalline powder (F types) 7.5g is obtained, yield is 75%.
Embodiment 2
10.0g Valsartans and ethanol/water (volume ratio 1: 1) mixed solvent 150mL are mixed to form suspension.Magnetic stir bar stirring is added,
Rotating speed is 200rpm, keeps stirring 3 days at ambient temperature.Suspension is filtered, and is washed with a small amount of ethanol/water (volume ratio 1: 1) mixed solvent
Afterwards, in reduced pressure at room temperature.White crystalline powder (F types) 8.1g is obtained, yield is 81%.
Claims (6)
1. a kind of ethanolates F crystal formations of Valsartan, it is characterised in that the X-ray powder diffraction represented with 2 θ angles is about：8.22,8.84,9.80,
11.15,12.97,12.42,14.22,14.52,14.94,15.86,16.93,17.33,18.01,18.61,19.30,19.70,21.08,
22.51,23.12,23.71,24.10,24.76,26.17,27.28,26.57,30.46,35.29 ° have characteristic absorption peak.
2. F crystal formations according to claim 1, it is characterised in that differential scanning calorimetric analysis have feature endothermic peak at about 103.1 DEG C.
3. F crystal formations according to claim 1, it is characterised in that the type crystal is orthorhombic system, space
Group is P2 (1) 2 (1) 2 (1), and cell parameter is：
α=β=γ=90 °, unit cell volume is：
4. the preparation method of F crystal formations according to claim 1, it is characterized in that this method comprises the following steps：
(1) it is suspended：Under room temperature to solvent boiling point temperature conditionss, Valsartan and solvent are suspended；
(2) stir：Above-mentioned suspension is stirred with magnetic stir bar, rotating speed is 55-550rpm, mixing time is 3-6 days；
(3) dry：Above-mentioned suspension is filtered, after being washed with solvent, in the ethanolates F crystal formations crystallization of room temperature to 100 DEG C of normal pressure drying Valsartans.
5. the preparation method of F crystal formations according to claim 4, wherein it is described be made into Valsartan it is molten used in suspension
Agent is methanol；Or, ethanol and methanol, acetone, acetonitrile, ether, tetrahydrofuran, n-hexane, normal heptane or the mixture of water formation.
6. purposes of the F crystal formations according to claim 1 in the medicine as angiotensin-ii antagonist is prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610250332.4A CN107304190A (en) | 2016-04-18 | 2016-04-18 | A kind of preparation method of crystalline form of Valsartan |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610250332.4A CN107304190A (en) | 2016-04-18 | 2016-04-18 | A kind of preparation method of crystalline form of Valsartan |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107304190A true CN107304190A (en) | 2017-10-31 |
Family
ID=60151798
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610250332.4A Pending CN107304190A (en) | 2016-04-18 | 2016-04-18 | A kind of preparation method of crystalline form of Valsartan |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107304190A (en) |
-
2016
- 2016-04-18 CN CN201610250332.4A patent/CN107304190A/en active Pending
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20171031 |