CN105622499A - New crystal of apatinib sulfate - Google Patents
New crystal of apatinib sulfate Download PDFInfo
- Publication number
- CN105622499A CN105622499A CN201410583111.XA CN201410583111A CN105622499A CN 105622499 A CN105622499 A CN 105622499A CN 201410583111 A CN201410583111 A CN 201410583111A CN 105622499 A CN105622499 A CN 105622499A
- Authority
- CN
- China
- Prior art keywords
- handkerchief
- sulphuric acid
- buddhist nun
- crystal forms
- novel crystal
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a new crystal of apatinib sulfate; the new crystal has an XRPD pattern having diffraction peaks at 2 theta values approximately: 6.32, 7.222, 12.139, 12.659, 13.581, 14.499, 15.479, 16.062, 16.682, 17.36, 17.815, 18.318, 18.659, 19.24, 19.66, 20.42, 21.178, 22.203, 22.877, 23.897, 24.42, 25.261, 26.661, 27.841, 30.061 and 30.859, wherein a 2 theta value error range is 0.2. The new crystal C has the advantages that the obtained crystal C of apatinib sulfate is a hydrate, has the stability superior to that of an amorphous form, and has good solubility.
Description
Technical field
The present invention relates to a kind of sulphuric acid Ah handkerchief novel crystal forms for Buddhist nun.
Background technology
A Pa is N-[4-(1-cyan cyclopentyl) phenyl]-2-(4-picolyl) amino-Niacinamide for Buddhist nun's chemical name, it it is a kind of molecular targeted antitumor drug, by a kind new medicine of Hengrui Medicine Co., Ltd., Jiangsu Prov.'s independent research, have the little molecule VEGF tyrosine kinase inhibitor of independent intellectual property right.
Result of study shows, the existence of material, i.e. the crystal formation of medicine, is the key factor affecting curative effect of medication. Same medicine, crystal formation is different, and its bioavailability is likely to can exist difference, and additionally its stability, mobility, compressibility are likely to meeting difference, and the application of medicine is produced important impact by these physicochemical properties. It is true that several times even Different therapeutical effect of decades of times can be produced when the medicine of different crystal forms uses clinically, such as chloromycetin.
Patent CN101676267B discloses the salt of a kind of N-[4-(1-cyan cyclopentyl) phenyl]-2-(4-picolyl) amino-Niacinamide, especially its hydrochlorate and mesylate.
Patent CN1502608A discloses has the six Yuans amino amides analog derivatives suppressing angiogenic activity, the preparation method that it discloses N-[4-(1-cyan cyclopentyl) phenyl]-2-(4-picolyl) amino-3-pyridine carboxamides, can become salt with sulphuric acid further.
Although above-mentioned patent has related to sulphuric acid Ah handkerchief for Buddhist nun, but have referred only compound itself, it does not have disclose its crystal formation, characterize also without collection of illustrative plates, and present patent application proposes the sulphuric acid Ah handkerchief novel crystal forms for Buddhist nun's compound. Yet there are no the sulphuric acid Ah handkerchief Patents for Buddhist nun's crystal formation.
Summary of the invention
It is an object of the invention to provide a kind of sulphuric acid Ah handkerchief novel crystal forms for Buddhist nun, crystal C.
The technical scheme realizing the object of the invention is: a kind of sulphuric acid Ah handkerchief is for the novel crystal forms of Buddhist nun, it is characterized in that: XRPD collection of illustrative plates is approximately 6.32,7.222,12.139,12.659,13.581,14.499,15.479,16.062,16.682,17.36,17.815,18.318,18.659,19.24,19.66,20.42,21.178,22.203,22.877,23.897,24.42,25.261,26.661,27.841,30.061,30.859 places in 2 �� values diffraction maximum, wherein 2 �� value range of error are 0.2.
The present invention a kind of sulphuric acid Ah handkerchief, for the preparation method of Buddhist nun's novel crystal forms, concretely comprises the following steps: weigh 500mg sulphuric acid Ah handkerchief for Buddhist nun in container, addition 100mL dichloromethane solvent, and 35 DEG C of suspension 48h obtain white powder after filtration, vacuum drying.
Weighing 500mg sulphuric acid Ah handkerchief replaces Buddhist nun in container, add the single solvent in 100mL tetramethyl tert-butyl group butyl ether and hexamethylene or mixed solvent, adopt ultrasonic echography 30min, after static 10min, continue ultrasonic 30min, after filtration, vacuum drying, obtain white powder.
It is an advantage of the current invention that: the sulphuric acid Ah handkerchief that the present invention obtains is monohydrate for Buddhist nun's crystal C, and its stability is better than unformed, and dissolubility is good. Experiments show that: unformed meeting is converted into crystal C under certain conditions.
Accompanying drawing explanation
Fig. 1 is the crystal C sulphuric acid Ah handkerchief XRPD collection of illustrative plates for Buddhist nun.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further described.
Embodiment 1. sulphuric acid Ah handkerchief is for the preparation of Buddhist nun's novel crystal forms
Weigh 500mg sulphuric acid Ah handkerchief for Buddhist nun in container, addition 100mL dichloromethane solvent, 35 DEG C of suspension 48h, obtain white powder after filtration, vacuum drying, detect through XRPD, collection of illustrative plates is Fig. 1 such as, and this novel crystal forms is crystal C.
Embodiment 2. sulphuric acid Ah handkerchief is for the preparation of Buddhist nun's novel crystal forms
Weighing 500mg sulphuric acid Ah handkerchief replaces Buddhist nun in container, add the single solvent in 100mL tetramethyl tert-butyl group butyl ether and hexamethylene or mixed solvent, adopt ultrasonic echography 30min, ultrasonic 30min is continued after static 10min, white powder is obtained after filtration, vacuum drying, detecting through XRPD, collection of illustrative plates is Fig. 1 such as, and this novel crystal forms is crystal C.
From XRPD collection of illustrative plates, diffraction maximum is approximately 6.32,7.222,12.139,12.659,13.581,14.499,15.479,16.062,16.682,17.36,17.815,18.318,18.659,19.24,19.66,20.42,21.178,22.203,22.877,23.897,24.42,25.261,26.661,27.841,30.061,30.859 places in 2 �� values, and wherein 2 �� value range of error are 0.2.
Embodiment 3.C crystal formation sulphuric acid Ah handkerchief investigates for Buddhist nun's high-temperature stability
C crystal form sulphuric acid Ah handkerchief is placed in 60 for Buddhist nun's sampleoIn C baking oven, after 5 days, sample is taken out and carry out XRPD test, to investigate the sample stability of crystal form to temperature. It is shown that C crystal form sample is stable under this condition.
Embodiment 4.C crystal formation sulphuric acid Ah handkerchief replaces Buddhist nun's high humidity study on the stability
C crystal form sulphuric acid Ah handkerchief is placed under 92.5% damp condition for Buddhist nun's sample, after 5 days, sample is taken out and carry out XRPD test, to investigate the sample stability of crystal form to temperature. It is shown that C crystal form sample is stable under this condition.
Embodiment 5.C crystal formation sulphuric acid Ah handkerchief investigates for Buddhist nun's light durability
C crystal form sulphuric acid Ah handkerchief is placed under 4500lux intensity of illumination for Buddhist nun's sample, after 5 days, sample is taken out and carry out XRPD test, to investigate the sample stability of crystal form to temperature. It is shown that C crystal form sample is stable under this condition.
Claims (6)
1. a sulphuric acid Ah handkerchief is for the novel crystal forms of Buddhist nun, it is characterized in that: XRPD collection of illustrative plates is approximately 6.32,7.222,12.139,12.659,13.581,14.499,15.479,16.062,16.682,17.36,17.815,18.318,18.659,19.24,19.66,20.42,21.178,22.203,22.877,23.897,24.42,25.261,26.661,27.841,30.061,30.859 places in 2 �� values diffraction maximum, wherein 2 �� value range of error are 0.2.
2. a kind of sulphuric acid Ah handkerchief according to claim 1 is for the novel crystal forms of Buddhist nun, it is characterised in that: the sulphuric acid Ah handkerchief of novel crystal forms is placed in 60 for Buddhist nun's sampleoIn C baking oven, after 5 days, sample is taken out and carry out XRPD test.
3. a kind of sulphuric acid Ah handkerchief according to claim 1 is for the novel crystal forms of Buddhist nun, it is characterised in that: the sulphuric acid Ah handkerchief of novel crystal forms is placed under 92.5% damp condition for Buddhist nun's sample, after 5 days, sample is taken out and carry out XRPD test.
4. a kind of sulphuric acid Ah handkerchief according to claim 1 is for the novel crystal forms of Buddhist nun, it is characterised in that: the sulphuric acid Ah handkerchief of novel crystal forms is placed under 4500lux intensity of illumination for Buddhist nun's sample, after 5 days, sample is taken out and carry out XRPD test.
5. prepare the sulphuric acid Ah handkerchief as claimed in claim 1 method for the novel crystal forms of Buddhist nun, it is characterised in that: weigh 500mg sulphuric acid Ah handkerchief for Buddhist nun in container, addition 100mL dichloromethane solvent, 35 DEG C of suspension 48h, obtain white powder after filtration, vacuum drying.
6. prepare the sulphuric acid Ah handkerchief as claimed in claim 1 method for the novel crystal forms of Buddhist nun, it is characterized in that: weigh 500mg sulphuric acid Ah handkerchief and replace Buddhist nun in container, add the single solvent in 100mL tetramethyl tert-butyl group butyl ether and hexamethylene or mixed solvent, adopt ultrasonic echography 30min, continue ultrasonic 30min after static 10min, after filtration, vacuum drying, obtain white powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410583111.XA CN105622499A (en) | 2014-10-28 | 2014-10-28 | New crystal of apatinib sulfate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410583111.XA CN105622499A (en) | 2014-10-28 | 2014-10-28 | New crystal of apatinib sulfate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105622499A true CN105622499A (en) | 2016-06-01 |
Family
ID=56037884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410583111.XA Pending CN105622499A (en) | 2014-10-28 | 2014-10-28 | New crystal of apatinib sulfate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105622499A (en) |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020147198A1 (en) * | 2001-01-12 | 2002-10-10 | Guoqing Chen | Substituted arylamine derivatives and methods of use |
| WO2003048158A1 (en) * | 2001-12-04 | 2003-06-12 | Bristol-Myers Squibb Company | Glycinamides as factor xa inhibitors |
| CN1502608A (en) * | 2002-11-27 | 2004-06-09 | 南京凯衡科贸有限公司 | Hexavalent amino amidate derivative with function of inhibiting blood vessel growth activity |
| US20040259916A1 (en) * | 2003-06-16 | 2004-12-23 | Chen Guoqing P. | Six membered amino-amide derivatives an angiogenisis inhibitors |
| CN1671666A (en) * | 2002-07-31 | 2005-09-21 | 舍林股份公司 | Vegfr-2 and vegfr-3 inhibitory anthranylamidopyridines |
| CN101676267A (en) * | 2008-09-16 | 2010-03-24 | 江苏恒瑞医药股份有限公司 | N-4-(1-cyan cyclopentyl) phenyl-2-(4-picolyl) amidogen-3-pyridinecarboxamide salt |
| CN101675930A (en) * | 2008-09-16 | 2010-03-24 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treating hyperplasia diseases |
| CN102048737A (en) * | 2009-10-28 | 2011-05-11 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treating tumor diseases |
| CN104072411A (en) * | 2014-07-08 | 2014-10-01 | 上海宣创生物科技有限公司 | Mesylate C crystal form of amide derivatives as well as preparation method and application thereof |
| CN104086484A (en) * | 2014-07-08 | 2014-10-08 | 上海宣创生物科技有限公司 | Mesylate solvate crystal of nicotinamide derivatives and preparation method and application of mesylate solvate crystal |
-
2014
- 2014-10-28 CN CN201410583111.XA patent/CN105622499A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020147198A1 (en) * | 2001-01-12 | 2002-10-10 | Guoqing Chen | Substituted arylamine derivatives and methods of use |
| WO2003048158A1 (en) * | 2001-12-04 | 2003-06-12 | Bristol-Myers Squibb Company | Glycinamides as factor xa inhibitors |
| CN1671666A (en) * | 2002-07-31 | 2005-09-21 | 舍林股份公司 | Vegfr-2 and vegfr-3 inhibitory anthranylamidopyridines |
| CN1502608A (en) * | 2002-11-27 | 2004-06-09 | 南京凯衡科贸有限公司 | Hexavalent amino amidate derivative with function of inhibiting blood vessel growth activity |
| US20040259916A1 (en) * | 2003-06-16 | 2004-12-23 | Chen Guoqing P. | Six membered amino-amide derivatives an angiogenisis inhibitors |
| CN101676267A (en) * | 2008-09-16 | 2010-03-24 | 江苏恒瑞医药股份有限公司 | N-4-(1-cyan cyclopentyl) phenyl-2-(4-picolyl) amidogen-3-pyridinecarboxamide salt |
| CN101675930A (en) * | 2008-09-16 | 2010-03-24 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treating hyperplasia diseases |
| CN102048737A (en) * | 2009-10-28 | 2011-05-11 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition for treating tumor diseases |
| CN104072411A (en) * | 2014-07-08 | 2014-10-01 | 上海宣创生物科技有限公司 | Mesylate C crystal form of amide derivatives as well as preparation method and application thereof |
| CN104086484A (en) * | 2014-07-08 | 2014-10-08 | 上海宣创生物科技有限公司 | Mesylate solvate crystal of nicotinamide derivatives and preparation method and application of mesylate solvate crystal |
Non-Patent Citations (4)
| Title |
|---|
| 宋国胜等: "功率超声在结晶过程中应用的进展", 《应用声学》 * |
| 杜春华等: "物理场强化溶液结晶研究进展", 《现代化工》 * |
| 杜秋江,等: "紫外分光光度法测定原料药中阿帕替尼的含量", 《淮海工学院学报(自然科学版)》 * |
| 胡爱军等: "超声场强化溶液结晶研究进展", 《应用声学》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK1993360T3 (en) | SOLID FORMS OF N- [2,4-BIS (1,1-DIMETHYLETHYL) -5-HYDROXYPHENYL] -1,4-DIHYDRO-4-OXOQUINOLIN-3-CARBOXAMIDE | |
| IL258253A (en) | Pyrrolo[3,2-d]pyrimidine derivatives for the treatment of viral infections and other diseases | |
| JP2017222671A5 (en) | ||
| Tabarrini et al. | Structure− activity relationship study on anti-HIV 6-desfluoroquinolones | |
| WO2016119505A1 (en) | Pyrrole sulfonyl derivative, and preparation method and medical use thereof | |
| EA201201664A1 (en) | 6-CYCLOALKYL-1,5-DIHYDROPIPAZOLO [3,4-D] PYRIMIDIN-4-SHE DERIVATIVES AND THEIR APPLICATION AS PDE9A Inhibitors | |
| Mitra et al. | Nano indium oxide catalyzed tandem cyclization of amidine with nitroolefin | |
| MX2011007444A (en) | Quinazolinone derivatives useful as vanilloid antagonists. | |
| CN104072411A (en) | Mesylate C crystal form of amide derivatives as well as preparation method and application thereof | |
| EA201600113A1 (en) | NEW AZABENZIMIDAZOLES DERIVATIVES | |
| CN105622498A (en) | New crystal of apatinib sulfate | |
| Capdevila et al. | Coupling of tyrosine deprotonation and axial ligand exchange in nitrocytochrome c | |
| CN105541708A (en) | New crystal form of apatinib sulfate | |
| CN105622499A (en) | New crystal of apatinib sulfate | |
| JP2013530948A5 (en) | ||
| WO2011066864A1 (en) | Method and compositions for inhibition of macrophage migration inhibitory factor (mif) | |
| CN104072410A (en) | Mesylate D crystal form of nicotinamide derivatives and preparation method and application thereof | |
| CN108250138A (en) | A Pa is for Buddhist nun's A crystal forms and its preparation method and application | |
| CN104072412A (en) | Mesylate B crystal form of nicotinamide derivative, preparation method and application of mesylate B crystal form | |
| JP2017535562A (en) | Novel 1,3,5-triazine-based PI3K inhibitor as anticancer agent and method for producing the same | |
| CN114014824B (en) | Application of heterocyclic compound | |
| KR101372840B1 (en) | Process for preparing anhydrous aripiprazole crystal | |
| CN104193745B (en) | A kind of imidazopyrimidine carboxylic acid compound and preparation method thereof | |
| Machado et al. | 1-(7-Chloro-1, 4-dihydroquinolin-4-ylidene) thiosemicarbazide and its hydrochloride: evidence for the existence of a stable imine tautomer in the solid state of 4-aminoquinoline free bases, an anomalous case in nitrogen heterocycles | |
| CN108250139A (en) | A Pa is for Buddhist nun's B crystal form and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160601 |