CN103450119B - Cabazitaxel with crystal form W and method for preparing same - Google Patents
Cabazitaxel with crystal form W and method for preparing same Download PDFInfo
- Publication number
- CN103450119B CN103450119B CN201310440458.4A CN201310440458A CN103450119B CN 103450119 B CN103450119 B CN 103450119B CN 201310440458 A CN201310440458 A CN 201310440458A CN 103450119 B CN103450119 B CN 103450119B
- Authority
- CN
- China
- Prior art keywords
- degrees
- cabazitaxel
- crystal form
- crystal formation
- water
- 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 63
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 title claims abstract description 48
- 229960001573 cabazitaxel Drugs 0.000 title claims abstract description 48
- 238000000034 method Methods 0.000 title abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract description 4
- 239000008367 deionised water Substances 0.000 claims abstract description 3
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 3
- 238000005406 washing Methods 0.000 claims abstract description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 238000004140 cleaning Methods 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 abstract description 5
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract 5
- 230000007613 environmental effect Effects 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000001953 recrystallisation Methods 0.000 abstract 1
- 238000005755 formation reaction Methods 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- 238000002441 X-ray diffraction Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000000967 suction filtration Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 230000035800 maturation Effects 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910017488 Cu K Inorganic materials 0.000 description 1
- 229910017541 Cu-K Inorganic materials 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001946 anti-microtubular Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 229960003328 benzoyl peroxide Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 230000012106 negative regulation of microtubule depolymerization Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a cabazitaxel with a crystal form W and a method for preparing the cabazitaxel with the crystal form W. Characteristic peaks 2theta of an X-ray powder diffraction pattern of the cabazitaxel with the crystal form W is 4.4 degrees+/-0.2 degrees, 7.8 degrees+/-0.2 degrees, 8.5 degrees+/-0.2 degrees, 11.4 degrees +/-0.2 degrees, 12.8 degrees +/-0.2 degrees, 15.3 degrees +/-0.2 degrees, 17.0 degrees +/-0.2 degrees, 20.4 degrees +/-0.2 degrees, 21.4 degrees +/-0.2 degrees, 22.5 degrees +/-0.2 degrees, 23.4 degrees +/-0.2 degrees, 27.8 degrees +/-0.2 degrees, 29.7 degrees +/-0.2 degrees, 29.9 degrees +/-0.2 degrees, 33.3 degrees +/-0.2 degrees and 34.3 degrees +/-0.2 degrees. The method for preparing the cabazitaxel with the crystal form W includes the steps of dissolving cabazitaxel with any crystal form into a proper amount of organic solvents, then, slowly adding deionized water to the mixture while stirring the mixture, then, lowering the temperature of the mixture to the environmental temperature, standing the mixture till recrystallization, and filtering, washing and drying the mixture to obtain the cabazitaxel with the crystal form W. Compared with cabazitaxel with a crystal form reported in a known patent document, the cabazitaxel with the crystal form W has the great advantages of being stable in crystal form, simpler in preparing process, free of the harsh requirements on the environment and devices and strong in repeatability, and thereby being beneficial to industrial production.
Description
Technical field
The invention belongs to medical art, particularly relate to a kind of Cabazitaxel (cabazitaxel) crystal formation W and preparation method thereof.
Background technology
Cabazitaxel (cabazitaxel) belongs to yew alkanes antitumour drug, its chemistry 4-acetoxyl group-2 α-benzoyloxy-5 β by name, 20 epoxy-1-hydroxyl-7 β, 10 β-dimethoxy-9-oxo-11-Japanese yew alkene-13 α-Ji alcohol-(2R, 3S)-3-t-butoxycarbonyl amino-PLA ester.Structural formula is as shown in the formula shown in (I):
The mechanism of anticancer action of Cabazitaxel is similar to docetaxel with feature, belongs to anti-microtubule class medicine.With tubulin binding, it is by promoting that it is assembled into microtubule, the microtubule that simultaneously these can be stoped to have assembled disintegrates, and makes microtubule stabilization, and then the performance of the mitotic division of T suppression cell and Interphase cells function.
Crystal formation is one of important factor affecting drug quality, curative effect and preparation processing performance.In view of the curative effect that Cabazitaxel is good, people have carried out a lot of research to it, and have developed a lot of crystal formation.The Cabazitaxel crystal formation of existing bibliographical information is summed up roughly following a few class: solvate, anhydride, hydrate and amorphous article etc.In the crystal formation that Cabazitaxel is known, WO2005028462 reports crystal form A the earliest, and it is the acetone solvate form of Cabazitaxel, and the shortcoming of this crystal formation is unstable, easy partial removal acetone; Report crystal form B, C, D, E, F in Chinese patent CN101918385 subsequently, all can be transformed by crystal form A.Wherein B crystal form sample be A crystal form samples at high temperature de-acetone obtain, C crystal form sample is that A or B crystal form sample are carried out maturation process in water, then under maintenance low humidity 0-5%RH condition, obtains in 50 DEG C of heat dryings; Form D sample be A crystal form samples in oil (particularly neutral oil, as: median chain triglyceride oil Miglyol) turn crystal formation gained through heat treated; Crystal form E sample is A crystal form samples maturation process in ethanol/water, then high temperature removal solvation gained; F crystal form samples be by A crystal form samples in ethanol/water equal solvent through maturation process, then dryly under low moisture conditions remove that solvent obtains.There was reported the solvate of ethanol in Chinese patent CN101918385, B, D, E, F Cabazitaxel of different crystal forms simultaneously, in the saturated environment of alcohol vapour, through process, obtain B, D, E, F new crystal of alcohol solvent respectively; This patent there was reported the Cabazitaxel of monohydrate and dihydrate, obtains under different ambient moisturies by C crystal form sample.Unformed Cabazitaxel is reported by Chinese patent CN102659722, describes according to this patent, and unformed Cabazitaxel can be obtained by the method conversion of dissolving crystallization by the Cabazitaxel of any crystal formation.
In sum, we can find out that the preparation of all crystal formations of Cabazitaxel all needs specific environment to realize, be unfavorable for industrialization prepared by crystal formation like this, and the operation such as the such as high temperature desolventizing adopted in the preparation process of some crystal formation can cause the decline of product purity, and some crystal formation is not inherently very stable, be easy to occur polymorphism, thus directly can affect the preparation processing performance of medicine, and affect the solubleness of medicine, stability and bioavailability, and then have influence on the quality of medicine, security, validity and application.
Summary of the invention
In order to solve the problem, the object of the present invention is to provide a kind of good stability and Cabazitaxel crystal formation W being beneficial to suitability for industrialized production and preparation method thereof.
In order to achieve the above object, X-ray powder diffraction characteristic peak 2 θ of Cabazitaxel crystal formation W provided by the invention is 4.4,7.8,8.5,11.4,12.8,15.3,17.0,20.4,21.4,22.5,23.4,27.8,29.7,29.9,33.3 and 34.3 ± 0.2 °.
The preparation method of Cabazitaxel crystal formation W provided by the invention comprises the following step carried out in order:
1) Cabazitaxel of any crystal formation is dissolved in appropriate organic solvent, then slowly deionized water is added wherein while stirring, organic solvent is selected from least one in methyl alcohol, ethanol, Virahol or acetonitrile, the volume ratio of organic solvent and water is 55:45-85:15, then be down to envrionment temperature, leave standstill crystallization;
2) above-mentioned mixed solution is filtered, washing is also dry and obtain Cabazitaxel crystal formation W.
Described step 2) in cleaning solvent be the mixed solvent of water or water and alcohol, drying temperature is 40-50 DEG C.
Have great advantage in stability of crystal form compared with the crystal formation that Cabazitaxel crystal formation W provided by the invention and known patent document are reported, and the preparation process of this crystal formation is fairly simple, harsh requirement is not had to environment and equipment, repeatable strong, be therefore beneficial to suitability for industrialized production.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction of Cabazitaxel crystal formation W provided by the invention.
Fig. 2 is the DSC collection of illustrative plates of Cabazitaxel crystal formation W provided by the invention.
Embodiment
Below with reference to explanation the present invention that example is detailed, embodiments of the invention are only for illustration of technology bill of the present invention, and non-limiting the spirit and scope of the invention.
Test testing tool used:
1, x-ray diffraction pattern
INSTRUMENT MODEL: Bruker D8 type X-ray powder diffractometer
Ray: Cu-K α
1(λ=1.54056)
Scan mode: 2 θ=2-40 °, 0.01 °/1sec
Voltage: 40KV-40mA
2, DCS instrument
INSTRUMENT MODEL: TA instrument differential scanning calorimeter
Purging device: platinum dish, constant nitrogen gas stream
Temperature rise rate: 5 DEG C/min
Temperature range: 30-300 DEG C
Embodiment 1:
Taking Cabazitaxel pressed powder 500mg is dissolved in 10mL methyl alcohol, 5mL water is dropwise added wherein under stirring, then envrionment temperature is cooled to, leave standstill 24 hours crystallize outs, suction filtration, washes filter cake with water, obtains solid sample 490mg afterwards at the temperature of 40 DEG C after vacuum-drying, purity 99.7%, yield 95.6%.The X-ray of above-mentioned testing tool to this sample is utilized to test, X-ray diffraction spectrogram is shown in Fig. 1, the display of PXRD spectral characterization is positioned at the characteristic peak of 4.4,7.8,8.5,11.4,12.8,15.3,17.0,20.4,21.4,22.5,23.4,27.8,29.7,29.9,33.3 and 34.3 ± 0.2 ° of 2 θ, is judged as that this compound is Cabazitaxel crystal formation W.Its fusing point adopts DSC instrument to measure, and DSC spectrogram is shown in Fig. 2, and its fusing point is 153.78 DEG C.
Embodiment 2:
Taking Cabazitaxel pressed powder 500mg is dissolved in 10mL ethanol, 5mL water is dropwise added wherein under stirring, then envrionment temperature is cooled to, leave standstill 24 hours crystallize outs, suction filtration, washes filter cake with water, obtains solid sample 492mg afterwards at the temperature of 45 DEG C after vacuum-drying, purity 99.2%, yield 98.4%.The X-ray diffraction spectrogram of this sample and DSC spectrogram, through comparative study, determine that this compound is Cabazitaxel crystal formation W.
Embodiment 3:
Taking Cabazitaxel pressed powder 500mg is dissolved in 10mL Virahol, 5mL water is dropwise added wherein under stirring, then envrionment temperature is cooled to, leave standstill 24 hours crystallize outs, suction filtration, washes filter cake with water, obtains solid sample 460mg afterwards at the temperature of 50 DEG C after vacuum-drying, purity 99.3%, yield 92.0%.The X-ray diffraction spectrogram of this sample and DSC spectrogram, through comparative study, determine that this compound is Cabazitaxel crystal formation W.
Embodiment 4:
Taking Cabazitaxel pressed powder 500mg is dissolved in 10mL acetonitrile, 5mL water is dropwise added wherein at 50 DEG C, then envrionment temperature is cooled to, leave standstill 24 hours crystallize outs, suction filtration, washes filter cake with water, obtains solid sample 482mg afterwards at the temperature of 40 DEG C after vacuum-drying, purity 98.9%, yield 96.4%.The X-ray diffraction spectrogram of this sample and DSC spectrogram, through comparative study, determine that this compound is Cabazitaxel crystal formation W.
The Cabazitaxel crystal formation W outward appearance obtained by above-described embodiment is water white acicular crystals, and chemical stability is good, and after heat treated, physical and chemical states and the X-diffracting spectrum of crystal have no considerable change.This Cabazitaxel crystal formation W and known patent document report that table 1 is below shown in the X-diffracting spectrum characteristic peak of crystal formation and fusing point comparison.
Table 1
Claims (3)
1. a Cabazitaxel crystal formation W, is characterized in that: X-ray powder diffraction characteristic peak 2 θ of described Cabazitaxel crystal formation W is 4.4,7.8,8.5,11.4,12.8,15.3,17.0,20.4,21.4,22.5,23.4,27.8,29.7,29.9,33.3 and 34.3 ± 0.2 °.
2. a preparation method of Cabazitaxel crystal formation W according to claim 1, is characterized in that: described preparation method comprises the following step carried out in order:
1) Cabazitaxel of any crystal formation is dissolved in appropriate organic solvent, then slowly deionized water is added wherein while stirring, organic solvent is selected from least one in methyl alcohol, ethanol, Virahol or acetonitrile, the volume ratio of organic solvent and water is 55:45-85:15, then be down to envrionment temperature, leave standstill crystallization;
2) above-mentioned mixed solution is filtered, washing is also dry and obtain Cabazitaxel crystal formation W.
3. preparation method according to claim 2, is characterized in that: described step 2) in cleaning solvent be the mixed solvent of water or water and alcohol, drying temperature is 40-50 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310440458.4A CN103450119B (en) | 2013-09-24 | 2013-09-24 | Cabazitaxel with crystal form W and method for preparing same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310440458.4A CN103450119B (en) | 2013-09-24 | 2013-09-24 | Cabazitaxel with crystal form W and method for preparing same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103450119A CN103450119A (en) | 2013-12-18 |
| CN103450119B true CN103450119B (en) | 2015-06-17 |
Family
ID=49733010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310440458.4A Active CN103450119B (en) | 2013-09-24 | 2013-09-24 | Cabazitaxel with crystal form W and method for preparing same |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103450119B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105461664A (en) * | 2014-08-21 | 2016-04-06 | 中国医学科学院药物研究所 | Cabazitaxel N5 crystal form substance, and preparation method, composition and use thereof |
| CN105461665A (en) * | 2014-08-21 | 2016-04-06 | 中国医学科学院药物研究所 | Cabazitaxel N6 crystal form substance, and preparation method, composition and use thereof |
| CN105367521A (en) * | 2014-08-21 | 2016-03-02 | 中国医学科学院药物研究所 | Cabazitaxel N4 crystal form substance, and preparation method, composition and use thereof |
| CN108409691A (en) * | 2018-02-12 | 2018-08-17 | 江苏红豆杉药业有限公司 | A kind of Cabazitaxel crystal form HDC-1 and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101918385A (en) * | 2008-01-17 | 2010-12-15 | 安万特医药股份有限公司 | Crystalline forms of dimethoxy docetaxel and methods for preparing same |
| CN102746258A (en) * | 2012-07-25 | 2012-10-24 | 重庆泰濠制药有限公司 | Crystal forms of cabazitaxel and preparation method thereof |
| CN102898406A (en) * | 2012-11-02 | 2013-01-30 | 上海金和生物技术有限公司 | Cabazitaxel crystal and preparation method thereof |
| CN103058960A (en) * | 2012-12-12 | 2013-04-24 | 江苏奥赛康药业股份有限公司 | Cabazitaxel polymorphic form and preparation method thereof |
-
2013
- 2013-09-24 CN CN201310440458.4A patent/CN103450119B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101918385A (en) * | 2008-01-17 | 2010-12-15 | 安万特医药股份有限公司 | Crystalline forms of dimethoxy docetaxel and methods for preparing same |
| CN102746258A (en) * | 2012-07-25 | 2012-10-24 | 重庆泰濠制药有限公司 | Crystal forms of cabazitaxel and preparation method thereof |
| CN102898406A (en) * | 2012-11-02 | 2013-01-30 | 上海金和生物技术有限公司 | Cabazitaxel crystal and preparation method thereof |
| CN103058960A (en) * | 2012-12-12 | 2013-04-24 | 江苏奥赛康药业股份有限公司 | Cabazitaxel polymorphic form and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103450119A (en) | 2013-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103450119B (en) | Cabazitaxel with crystal form W and method for preparing same | |
| CN103880892B (en) | Acyl Ferrocene contracting S-methyldi-thiocarbazate Schiff and preparation method thereof | |
| EP2697236A1 (en) | Stannyl derivatives of naphthalene diimides and related compositions and methods | |
| EP2822932A2 (en) | Solid state forms of cabazitaxel and processes for preparation thereof | |
| CN108003149A (en) | A kind of canagliflozin crystal form I and preparation method thereof | |
| Chen et al. | A highly selective fluorescent sensor for Fe 3+ ion based on coumarin derivatives | |
| CN102250039A (en) | Ionic liquid of N-methyl piperazine salt and preparation method thereof | |
| CN104130192B (en) | Imidazolyl-benzaldehyde p-phenylenediamine bis-Schiff base and preparation method thereof | |
| CN107721839B (en) | Curcumin-4-aminophenol eutectic crystal and preparation method thereof | |
| CN103509031B (en) | Prepare the method for Prezista amorphous substance | |
| CN105294721B (en) | The synthesis of Yi Zhong perylene diimide derivatives and micro wire preparation method | |
| CN115385946B (en) | Iminoborates and methods of synthesis and use thereof | |
| CN106854203A (en) | Novel crystal forms of sufentanil citrate and preparation method thereof | |
| JP6929769B2 (en) | Crystals of 6-arylaminopyridone carboxamide compound and its production method | |
| CN114716503A (en) | Preparation method of wilfordii chlorine lactonic alcohol | |
| Xiao et al. | Self-assembly and optical properties of hydrogen bonded nanostructures containing C60 and pyrene | |
| CN108558690A (en) | The crystal form and preparation method thereof of seromycin carboxylate hydrochloride | |
| CN102321141B (en) | Amorphous substance of 17alpha-acetoxy-11beta-(4-N,N-dimethylaminophenyl)-19-norpregn-4,9-diene-3,20-diketone and preparation method thereof | |
| CN108409691A (en) | A kind of Cabazitaxel crystal form HDC-1 and preparation method thereof | |
| WO2015123801A1 (en) | Preparation method for polymorphic 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine and use thereof | |
| CN103012246B (en) | Double-branched chain aromatic amine and derivative and preparation method thereof | |
| CN102584570B (en) | Alpha-ketone-benzol lactamine calcium- hydrate crystal and preparation method thereof | |
| CN114591394B (en) | Nemactetvir crystal form and preparation method thereof | |
| CN105461686A (en) | Preparation method of high purity Pradaxa crystal form | |
| CN109320459A (en) | A kind of phenanthro- imidazole derivative containing fluorenes, crystal and the preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Cabazitaxel with crystal form W and method for preparing same Effective date of registration: 20151021 Granted publication date: 20150617 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2015990000906 |
|
| PLDC | Enforcement, change and cancellation of contracts on pledge of patent right or utility model | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20161017 Granted publication date: 20150617 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2015990000906 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Cabazitaxel with crystal form W and method for preparing same Effective date of registration: 20161017 Granted publication date: 20150617 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2016990000880 |
|
| PLDC | Enforcement, change and cancellation of contracts on pledge of patent right or utility model | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20171018 Granted publication date: 20150617 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2016990000880 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Cabazitaxel with crystal form W and method for preparing same Effective date of registration: 20171018 Granted publication date: 20150617 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2017990000966 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20181018 Granted publication date: 20150617 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2017990000966 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Cabazitaxel with crystal form W and method for preparing same Effective date of registration: 20181018 Granted publication date: 20150617 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2018990000977 |
|
| PM01 | Change of the registration of the contract for pledge of patent right |
Change date: 20210930 Registration number: 2018990000977 Pledgee after: Bank of Tianjin Co.,Ltd. second center sub branch Pledgee before: Bank of Tianjin Limited by Share Ltd. Tianma subbranch |
|
| PM01 | Change of the registration of the contract for pledge of patent right |