CN109956915B - 乙胺嗪晶型α及其制备方法 - Google Patents
乙胺嗪晶型α及其制备方法 Download PDFInfo
- Publication number
- CN109956915B CN109956915B CN201711404435.2A CN201711404435A CN109956915B CN 109956915 B CN109956915 B CN 109956915B CN 201711404435 A CN201711404435 A CN 201711404435A CN 109956915 B CN109956915 B CN 109956915B
- Authority
- CN
- China
- Prior art keywords
- degrees
- crystal form
- ethanamine
- ethazine
- ray powder
- 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.)
- Active
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 36
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 7
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000002844 melting Methods 0.000 claims description 5
- 230000008018 melting Effects 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000012360 testing method Methods 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 230000001133 acceleration Effects 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RMGHERXMTMUMMV-UHFFFAOYSA-N 2-methoxypropane Chemical compound COC(C)C RMGHERXMTMUMMV-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940043232 butyl acetate Drugs 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- OIIDNJKABGVNPQ-UHFFFAOYSA-N ethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound CCN.OC(=O)CC(O)(C(O)=O)CC(O)=O OIIDNJKABGVNPQ-UHFFFAOYSA-N 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 1
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了乙胺嗪晶型α及其制备方法，所述晶型的X射线粉末衍射中，2θ衍射角度在8.5±0.2°、12.7±0.2°、12.9±0.2°、13.2±0.2°、16.7±0.2°、17.2±0.2°、20.3±0.2°、25.8±0.2°、26.4±0.2°处有特征峰。与现有技术相比，本发明制备得到的乙胺嗪晶型α纯度更高，稳定性更好。
Description
技术领域
本发明涉及乙胺嗪晶型α及其制备方法。
背景技术
乙胺嗪即1-二乙胺基甲酰基-4-甲基哌嗪，是合成抗寄生虫病药——枸橼酸乙胺嗪的关键中间体。
DE923967C公开了乙胺嗪的结晶方法，用低沸点石油醚作为重结晶溶剂，乙胺嗪熔点为49-50℃，收率为62％。
SU1031963A1公开了乙胺嗪的结晶方法，使用丙酮作为重结晶溶剂，乙胺嗪熔点约为51-52℃。
目前，现有技术制备得到的乙胺嗪产品收率及纯度较低，稳定性较差。
因此，现在急需开发出一种收率和纯度更高，稳定性更好的乙胺嗪晶体。
发明内容
为了解决上述技术问题，本发明提供了乙胺嗪晶型α及其制备方法。
本发明首先提供了乙胺嗪晶型α，所述晶型的X射线粉末衍射中，2θ衍射角度在8.5±0.2°、12.7±0.2°、12.9±0.2°、13.2±0.2°、16.7±0.2°、17.2±0.2°、20.3±0.2°、25.8±0.2°、26.4±0.2°处有特征峰。
进一步地，所述X射线粉末衍射中，2θ衍射角度还在14.0±0.2°、17.9±0.2°、18.9±0.2°、22.0±0.2°、23.2±0.2°、23.9±0.2°、25.5±0.2°、28.5±0.2°处有特征峰。
进一步地，该晶型的X射线粉末衍射中，2θ衍射角度特征峰的相对强度值为：
进一步地，该晶型的熔点为49-50℃。
本发明还提供了制备乙胺嗪晶型α的方法，它包括以下步骤：
(1)将乙胺嗪溶解于有机溶剂中，所述有机溶剂不选自石油醚或丙酮中的任一种或其组合；
(2)于-20～20℃结晶；
(3)分离出晶体，干燥即得。
进一步地，步骤(1)中的溶解过程中，温度为10℃至溶剂的回流温度。
进一步地，步骤(1)中，所述溶剂选自正戊烷、正己烷、正庚烷、环戊烷、环己烷、环庚烷、丙醚、甲乙醚、异丙醚、甲基异丙基醚、甲基叔丁基醚、四氢呋喃、2-甲基四氢呋喃、四氢吡喃、甲基异丙基酮、甲基异丁基酮、1,4-二氧六环、甲酸乙酯、乙酸乙酯、乙酸丙酯、乙酸异丙酯、乙酸丁酯、乙酸异丁酯、乙酸叔丁酯、乙腈中的任一种或其组合；
进一步地，所述溶剂与乙胺嗪的体积重量比为0.5～5mL/g。
试验结果证明，本发明制备得到的乙胺嗪晶型α比现有的乙胺嗪晶型具有更高的纯度以及更好的稳定性。
显然，根据本发明的上述内容，按照本领域的普通技术知识和惯用手段，在不脱离本发明上述基本技术思想前提下，还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1为本发明乙胺嗪晶型α的XRPD图。
图2为对比例1中乙胺嗪对照晶型的XRPD图。
具体实施方式
实施例1、本发明晶型α的制备
取10.0g乙胺嗪粗品加入到50mL环己烷中，加热搅拌溶清。降温至-20℃析晶。过滤，固体于35℃真空干燥，得到8.4g乙胺嗪晶型α。收率84.0％，化学纯度99.98％，XRPD图谱如图1所示，XRPD数据如表1所示。
表1本发明乙胺嗪晶型α的XRPD数据
实施例2、本发明晶型α的制备
取15.5g乙胺嗪粗品加入8mL甲基叔丁基醚中，加热搅拌溶清。降温至-10℃，析晶。过滤，固体于30℃真空干燥，得到12.8g乙胺嗪晶型α。收率82.6％，化学纯度99.96％。
实施例3、本发明晶型α的制备
取20.4g乙胺嗪粗品加入到50mL甲基异丙基酮中，加热搅拌溶清。降温至10℃，析晶。过滤，固体于25℃真空干燥，得到16.4g乙胺嗪晶型α。收率80.4％，化学纯度99.97％。
实施例4、本发明晶型α的制备
取27.6g乙胺嗪粗品加入到30mL乙酸乙酯中，加热搅拌溶清。降温至0℃，析晶。过滤，固体于20℃真空干燥，得到22.6g乙胺嗪晶型α。收率81.9％，化学纯度99.99％。
以下通过试验例的方式来具体说明本发明的有益效果。
对比例1
取将10.0g乙胺嗪粗品用石油醚重结晶，得到6.7g乙胺嗪对照晶型，熔点48-50℃。收率67.0％，化学纯度99.55％(参考DE923967C)，其XRPD图谱如图2所示，XRPD数据如表2所示。
表2乙胺嗪对照晶型的XRPD数据
试验例1、晶型的稳定性评价
1)实验材料
实施例4制备的乙胺嗪晶型α；对比例制备的乙胺嗪晶型。
2)实验方法与结果
试验方法参见《中国药典(2015)》第四部9001《原料药物与制剂稳定性试验指导原则》。
影响因素试验：
①高温试验：取乙胺嗪对照晶型以及实施例4乙胺嗪晶型α，于40℃温度下放置10天，于第5天和第10天取样，测定各项指标与0天样品进行比较(HPLC法)，试验结果见表3。
②强光照射试验：取乙胺嗪对照晶型以及实施例4乙胺嗪晶型α，于照度为(4500±500)lx的条件下放置10天，于第5天和第10天取样，测定各项指标与0天样品进行比较(HPLC法)，试验结果见表3。
表3乙胺嗪晶型影响因素试验结果
加速试验：
将制得的乙胺嗪对照晶型以及实施例4乙胺嗪晶型α在恒温恒湿箱中进行6个月的加速试验。试验条件是：(25±2)℃/RH(60±5)％，分别于0、1、2、3、6个月取样，进行化学纯度和杂质检验(HPLC法)，结果见表4。
表4乙胺嗪晶型加速试验结果
从表3和表4可知，本发明乙胺嗪晶型α的稳定性比对照晶型好，特别是在光照条件下，本发明乙胺嗪晶型α的稳定性与对照晶型相比有明显的提高。
综上，本发明制备得到了纯度更高，稳定性更好的乙胺嗪新晶型。
Claims (5)
1.乙胺嗪晶型α，其特征在于：所述晶型的X射线粉末衍射中，2θ衍射角度在8.5±0.2°、12.7±0.2°、12.9±0.2°、13.2±0.2°、16.7±0.2°、17.2±0.2°、20.3±0.2°、25.8±0.2°、26.4±0.2°处有特征峰；所述X射线粉末衍射中，2θ衍射角度还在14.0±0.2°、17.9±0.2°、18.9±0.2°、22.0±0.2°、23.2±0.2°、23.9±0.2°、25.5±0.2°、28.5±0.2°处有特征峰；该晶型的X射线粉末衍射中，2θ衍射角度特征峰的相对强度值为：
2.根据权利要求1所述的乙胺嗪晶型α，其特征在于：该晶型的熔点为49-50℃。
3.一种制备权利要求1或2所述乙胺嗪晶型α的方法，其特征在于：它包括以下步骤：
(1)将乙胺嗪溶解于有机溶剂中，所述有机溶剂为环己烷、甲基叔丁基醚、甲基异丙基酮、乙酸乙酯；
(2)于-20～20℃结晶；
(3)分离出晶体，干燥即得。
4.根据权利要求3所述的方法，其特征在于：步骤(1)中的溶解过程中，温度为10℃至溶剂的回流温度。
5.根据权利要求3或4所述的方法，其特征在于：步骤(1)中，所述溶剂与乙胺嗪的体积重量比为0.5～5mL/g。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711404435.2A CN109956915B (zh) | 2017-12-22 | 2017-12-22 | 乙胺嗪晶型α及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711404435.2A CN109956915B (zh) | 2017-12-22 | 2017-12-22 | 乙胺嗪晶型α及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109956915A CN109956915A (zh) | 2019-07-02 |
| CN109956915B true CN109956915B (zh) | 2023-10-24 |
Family
ID=67019386
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711404435.2A Active CN109956915B (zh) | 2017-12-22 | 2017-12-22 | 乙胺嗪晶型α及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109956915B (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2643255A (en) * | 1948-10-30 | 1953-06-23 | Union Chimique Belge Sa | Method of preparing piperazine compounds and a new type of compound produced thereby |
| DE923967C (de) * | 1951-06-14 | 1955-02-24 | Bayer Ag | Verfahren zur Herstellung von tetrasubstituierten Harnstoffen |
| SU1031963A1 (ru) * | 1981-08-06 | 1983-07-30 | Rutman Iosif M | Способ получени 1-диэтилкарбамил-4-метилпиперазина |
-
2017
- 2017-12-22 CN CN201711404435.2A patent/CN109956915B/zh active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2643255A (en) * | 1948-10-30 | 1953-06-23 | Union Chimique Belge Sa | Method of preparing piperazine compounds and a new type of compound produced thereby |
| DE923967C (de) * | 1951-06-14 | 1955-02-24 | Bayer Ag | Verfahren zur Herstellung von tetrasubstituierten Harnstoffen |
| SU1031963A1 (ru) * | 1981-08-06 | 1983-07-30 | Rutman Iosif M | Способ получени 1-диэтилкарбамил-4-метилпиперазина |
Non-Patent Citations (1)
| Title |
|---|
| S. KUSHNER et al.."EXPERIMENTAL CHEMOTHERAPY OF FILARIASIS. V. THE PREPARATION OF DERIVATIVES OF PIPERAZINE".《Journal of Organic Chemistry》.1948,第第13卷卷第144-149页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109956915A (zh) | 2019-07-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2722496C (en) | Crystalline minocycline base and processes for its preparation | |
| EP3248983B1 (en) | Crystal form a of obeticholic acid and preparation method therefor | |
| WO2012077138A1 (en) | Methods of crystallizing (r) -1- (3 -hydroxypropyl) -5- [2- [2- [2- ( 2, 2, 2 - trifluoroethoxy) phenoxy] ethylamino] propyl] indoline-7 -carboxamide | |
| EP2612855A1 (en) | Novel crystal of erlotinib base and the preparation method thereof | |
| US20060074059A1 (en) | Isomorphic crystalline habits of 3alpha-hydroxy-21-(1'-imidazolyl)-3beta-methoxymethyl-5alpha-pregnane-20-one | |
| CN109956915B (zh) | 乙胺嗪晶型α及其制备方法 | |
| CN108440626B (zh) | 阿糖胞苷5′-o-l-缬氨酸酯盐酸盐的晶型及其制备方法 | |
| CN103596927A (zh) | 用于合成7-氯-4-(哌嗪-1-基)-喹啉的新方法 | |
| CN115925654A (zh) | 一种替马他赛化合物晶型及其制备方法和用途 | |
| WO2008089556A1 (en) | A novel crystalline mycophenolate sodium polymorph and processes to manufacture same | |
| US9127018B2 (en) | Solid forms of ortataxel | |
| CN108570045B (zh) | 氢溴酸山莨菪碱的晶型、其制备方法、药物组合物 | |
| CN108558690B (zh) | 环丝氨酸酯化物盐酸盐的晶型及其制备方法 | |
| KR20120096200A (ko) | 결정형 도세탁셀 및 이의 제조방법 | |
| CN114315944A (zh) | 泼尼松龙二水合物及其制备方法和应用 | |
| US20080182998A1 (en) | Novel crystalline mycophenolate sodium polymorph and processes to manufacture same | |
| EP3473623B1 (en) | Crystal forms of nbi-98854, preparation method therefor and use thereof | |
| WO2018054270A1 (zh) | 一种维帕他韦新晶型及其制备方法 | |
| CN115745913B (zh) | 曲法罗汀多晶型及其制备方法 | |
| WO2018198101A2 (en) | Processes for the preparation of crystalline form of eluxadoline | |
| CN111217781B (zh) | 贝前列素-314d晶体和其制备方法 | |
| CN110818676A (zh) | 一种环己烷衍生物的晶型 | |
| CN111533704B (zh) | 冷却结晶调控申嗪霉素晶型的方法 | |
| CN108558654B (zh) | 吉非罗齐晶型ⅰ的制备方法 | |
| WO2008110357A1 (en) | Method for preparing a flupirtine maleate of a crystal modification b |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 646100 Industrial Park, Fu Zhen Town, Luzhou, Sichuan, Luxian County Applicant after: Luzhou kered Pharmaceutical Co.,Ltd. Address before: 646106 Industrial Park, Fu Zhen Town, Luzhou, Sichuan, Luxian County Applicant before: SICHUAN CREDIT CHEMWERTH PHARMACEUTICAL Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20211018 Address after: 200000 floor 20, No. 1326, Yan'an west road, Changning District, Shanghai Applicant after: Kemus medical technology (Shanghai) Co.,Ltd. Address before: 646100 Industrial Park, Fu Zhen Town, Luzhou, Sichuan, Luxian County Applicant before: Luzhou kered Pharmaceutical Co.,Ltd. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |