CN108727387A - According to Shandong for Buddhist nun's isopropyl acetate solvent compound and preparation method thereof - Google Patents
According to Shandong for Buddhist nun's isopropyl acetate solvent compound and preparation method thereof Download PDFInfo
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- CN108727387A CN108727387A CN201810822751.XA CN201810822751A CN108727387A CN 108727387 A CN108727387 A CN 108727387A CN 201810822751 A CN201810822751 A CN 201810822751A CN 108727387 A CN108727387 A CN 108727387A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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Abstract
The present invention relates to one kind replacing Buddhist nun's isopropyl acetate solvent compound and preparation method according to Shandong, indicates there is characteristic peak at 7.3 ± 0.2 °, 7.7 ± 0.2 °, 8.9 ± 0.2 °, 10.2 ± 0.2 °, 14.6 ± 0.2 °, 15.6 ± 0.2 °, 17.1 ± 0.2 °, 18.2 ± 0.2 °, 18.9 ± 0.2 °, 20.5 ± 0.2 °, 21.2 ± 0.2 °, 21.8 ± 0.2 °, 22.6 ± 0.2 °, 24.9 ± 0.2 °, 27.0 ± 0.2 °, 27.6 ± 0.2 ° with 2 θ of X-ray powder diffraction.Product heap density is 0.6584g/mL, and angle of repose is 26 °, and preparation method is simple, and ultrasonic wave added constant temperature suspension turn crystalline substance can be used and prepare, also it can be prepared by crystallisation by cooling, products obtained therefrom crystallinity is high, and there is complete blocky crystalline substance to practise, good fluidity, heap density is high, is not easy to coalesce.
Description
Technical field
The invention belongs to medical crystallization technique fields, and in particular to replace Buddhist nun's isopropyl acetate solvent compound and its system according to Shandong
Preparation Method.
Background technology
It is by biopharmaceutical company of the U.S. (Pharmacyclics Inc) and Johnson & Johnson to replace Buddhist nun (Ibrutinib) according to Shandong
(Johnson&Johnson) develop jointly, 2013 Food and Drug Adminstration of the US on November 13, (FDA) ratify its conduct for the first time
Treat the drug listing of lymphoma mantle cell.The compound is a kind of small molecule bruton's tyrosine kinase (BTK, Bruton's
Tyrosine kinase) inhibitor, can with the cysteine residues covalent bond in the activated centres BTK, to inhibit B cell
Proliferation, existence.Its chemical name is 1-, [[4- amino -3- (4- Phenoxyphenyls) -1H- pyrazolos [3,4-D] are phonetic by (3R) -3-
Pyridine -1- bases] -1- piperidyls] -2- propylene -1- ketone, molecular formula C25H24N6O2, chemical structural formula is as follows：
Polymorphic refers to that there are different molecules aligns either conformations in its lattice for same substance, so as to cause formation
Crystal structure it is different.In drug research field, broad sense polymorphic includes the multicomponents crystal shape such as solvated compounds, hydrate
Formula.The different crystal form of same drug has aobvious in color, solubility, fusing point, dissolution rate, mobility, biological effectiveness etc.
The difference of work, and then influence stability, bioavilability and the curative effect of drug.It therefore, should be comprehensive in drug development process
Study its polymorphic problem.
According to Shandong, for Buddhist nun, there are multi-solvents compound and non-compound solid form, biopharmaceutical companys of the U.S. Yuan Yan
(Pharmacyclics Inc) is protected in 2013184572 A1 of world patent WO of its application and is replaced three kinds of non-solvents of Buddhist nun according to Shandong
Compound crystal form and three kinds of solvated compounds, wherein crystal form A, crystal form B and crystal form C are non-solvent compound crystal form, crystal form D, crystalline substance
Type E and crystal form F is respectively hexone solvated compounds, toluene solvant compound and methanol solvate compound, patent
2015081180 A1 of WO protect another to replace Buddhist nun's non-solvent compound crystal form I, Chinese patent CN according to Shandong
103923084A protect according to Shandong for Buddhist nun's non-solvent compound crystal form II, hydrate crystal forms III, tetrahydrofuran solvent compound with
And chloroform solvated compounds.The world patent WO 2015145415 A2 protections of Italian PERRIGO API LTD applications
It is a kind of to replace Buddhist nun's non-solvent compound, i.e. crystal form VI and six kinds of solvated compounds, i.e. Isosorbide-5-Nitrae-dioxane solvent chemical combination according to Shandong
Object crystal form III, glycol dimethyl ether solvated compounds crystal form IV, methanol solvate compound crystal form V, methyl phenyl ethers anisole solvated compounds are brilliant
Type VII, chlorobenzene solvent compound crystal form VIII and methyl phenyl ethers anisole solvated compounds crystal form IX.Presently commercially available replaces Buddhist nun's raw produce according to Shandong
Crystal form grinds that the crystal form A of report is consistent, and product particle size is small with original, does not have well-regulated shape, and poor fluidity, heap density is low, holds
Easily coalescence has difficulties in terms of the post-processings processing such as filtering, refined.In addition, the preparation method behaviour of crystal form A disclosed in patent
Work is complicated, time-consuming, is unfavorable for industrial production.The a variety of of existing patent report replace Buddhist nun's solvated compounds crystal form according to Shandong, are preparing
The solvent used in the process belongs to the first kind, the second class solvent, has certain toxicity, is unsuitable for being used for medicinal purpose crystal form.
Invention content
In order to overcome drawback of the existing technology, current commercial product poor fluidity, easy agglomeration problem are solved, needs to lead to
High-throughput crystal form samples screening means are crossed, different crystallization modes, ultrasonic wave added, single solvent and mixed solvent, non-equality of temperature are investigated
The influence of degree and stirring condition to final products crystal form, combining powder diffraction, single crystal diffraction, thermogravimetic analysis (TGA) and differential scanning amount
A variety of analysis test methods such as heat analysis develop simple controllable, safety and low toxicity processing technology routine, prepare and find new tool
There are the crystal form and solvated compounds of excellent performance, is conducive to Subsequent pharmacological and develops.
The present invention provides it is a kind of have it is blocky brilliant practise, be not easy to coalesce replace Buddhist nun's solvated compounds and its preparation side according to Shandong
Method.
It is provided by the invention to replace Buddhist nun's isopropyl acetate solvent compound according to Shandong, which is characterized in that be measured using Cu-K alpha rays
Obtained X-ray powder diffraction pattern is shown in attached drawing 1, with 2 θ of the angle of diffraction indicate 7.3 ± 0.2 °, 7.7 ± 0.2 °, 8.9 ± 0.2 °,
10.2±0.2°、14.6±0.2°、15.6±0.2°、17.1±0.2°、18.2±0.2°、18.9±0.2°、20.5±0.2°、
There is characteristic peak at 21.2 ± 0.2 °, 21.8 ± 0.2 °, 22.6 ± 0.2 °, 24.9 ± 0.2 °, 27.0 ± 0.2 °, 27.6 ± 0.2 °,
The relative intensity of characteristic peak is 100% at wherein 18.9 ± 0.2 °.
Provided by the invention to replace Buddhist nun's isopropyl acetate solvent compound, the crystal form according to Shandong be anorthic system, and space group is
P1, cell parameter areα=81.21 (3) °, β=69.22
(3) °, γ=69.88 (3) °, unit cell volume is
It is provided by the invention to replace Buddhist nun's isopropyl acetate solvent compound according to Shandong, according to Shandong for Buddhist nun and isopropyl acetate solvent molecule
Molar ratio be 1:1, theoretical weightlessness 18.8%, molecular formula C25H24N6O2·C5H10O2, in thermogravimetric analysis before 200 DEG C of temperature
16.9%~18.2% weightlessness is had, practical weightlessness matches with theoretical weightlessness.Specific weight loss depends on drying temperature
And drying time.
The preparation method provided by the invention that Buddhist nun's isopropyl acetate solvent compound is replaced according to Shandong is outstanding by ultrasonic wave added constant temperature
It is floating to turn brilliant realization：It will be added in 25 DEG C~40 DEG C of isopropyl acetate solvent for Buddhist nun's raw material according to Shandong, Buddhist nun's solid material replaced according to Shandong
Mass ratio with isopropyl acetate solvent is 1:Stir 20h~for 24 hours after 50~60, ultrasonic 20min~30min, filtering, dry
Buddhist nun's isopropyl acetate solvent compound is replaced to according to Shandong.
The supersonic frequency is 20~40KHz, ultrasonic power 100~300W/mL solution.
The drying condition is temperature at 20~30 DEG C, dry 7~10h under condition of normal pressure.
It is provided by the invention according to Shandong for Buddhist nun's isopropyl acetate solvent compounds process for production thereof be in external ultrasonic field and constant temperature
It suspends and turns to make crystals molecules align mode and conformation change under brilliant synergy, the cavitation generated using ultrasound
Localized hyperthermia, high pressure, the state of high shear are formed, nucleation, the growth for replacing Buddhist nun's isopropyl acetate solvent compound according to Shandong are promoted.
It suspends under turn brilliant experiment condition in conventional constant temperature, can not successfully prepare and replace Buddhist nun's isopropyl acetate solvent compound according to Shandong.
Contrast experiment illustrates that external ultrasound field is added has necessity to the preparation of novel crystal forms.
It is provided by the invention to replace Buddhist nun's isopropyl acetate solvent compound according to Shandong, the method system of crystallisation by cooling can also be passed through
It is standby, it will be dissolved in 40 DEG C~50 DEG C of isopropyl acetate solvent for Buddhist nun's solid material according to Shandong, it is different for Buddhist nun's raw material and acetic acid according to Shandong
The mass ratio of propyl ester is 1:70~90, -10 DEG C~10 DEG C are cooled to the rate of temperature fall of 1 DEG C/min~5 DEG C/min, is precipitated brilliant
Body, is obtained by filtration white solid, 5~10h of constant pressure and dry at 25~30 DEG C, obtains described replacing Buddhist nun's isopropyl acetate solvent according to Shandong
Close object.
Provided by the invention suspend for the ultrasonic wave added constant temperature of Buddhist nun's isopropyl acetate solvent compound according to Shandong turns brilliant and cooling
Crystallization preparation method, compared to other preparation processes, mild condition is easy to prepare；Selected solvent is three classes solvent acetic acid isopropyl
Ester, toxicity are low.
To being investigated for brilliant practise of Buddhist nun's isopropyl acetate solvent compound products according to Shandong, products obtained therefrom is presented the present invention
Bulk, crystalline substance is practised completely, and plane of crystal is bright and clean, and no agglomeration phenomena, scanning electron microscope (SEM) photograph is shown in attached drawing 2, the crystal form product heap density
For 0.6584g/mL, angle of repose is 26 °.Commercial product heap density is 0.5248g/mL, and angle of repose is 37 °, scanning electron microscope (SEM) photograph
See attached drawing 3.Compared to commercial product, crystal product provided by the invention improves the heap density and stream of product to a certain extent
Dynamic property.
The present invention according to Shandong for the stability of Buddhist nun's isopropyl acetate solvent compound to being investigated, by the isopropyl acetate
Ester solvent compound products are uniformly split in open culture dish, and control temperature is at 25 DEG C, and humidity 50%, thickness of sample is small
In 5mm, sealing, which is placed in drier, places 30 days, then to place 7 days, 14 days, 30 days samples carry out XRD detections respectively,
And it is compared with the 0th day testing result.Specific collection of illustrative plates is shown in attached drawing 4, and as a result showing XRD spectrum, there is no significant change, cards
Ming Yilu is preferable for Buddhist nun's isopropyl acetate solvent compound stability.
Description of the drawings
Fig. 1 present invention replaces the x-ray diffraction pattern of Buddhist nun's isopropyl acetate solvent compound according to Shandong.
Fig. 2 present invention replaces the scanning electron microscope (SEM) photograph of Buddhist nun's isopropyl acetate solvent compound according to Shandong.
The commercially available scanning electron microscope (SEM) photographs that Buddhist nun's product is replaced according to Shandong of Fig. 3.
Fig. 4 present invention according to Shandong replace Buddhist nun's isopropyl acetate solvent compound stability test trace analysis, wherein from it is lower to
On be followed successively by and place 0 day, 7 days, 14 days, the XRD spectras of 30 days samples.
What is prepared in Fig. 5 embodiments 1 replaces the thermogravimetric analysis collection of illustrative plates of Buddhist nun's isopropyl acetate solvent compound according to Shandong.
What is prepared in Fig. 6 embodiments 4 replaces the thermogravimetric analysis collection of illustrative plates of Buddhist nun's isopropyl acetate solvent compound according to Shandong.
What is prepared in Fig. 7 embodiments 6 replaces the thermogravimetric analysis collection of illustrative plates of Buddhist nun's isopropyl acetate solvent compound according to Shandong.
Specific implementation mode
Below by by the specific implementation mode of embodiment form, the above of the present invention is made further specifically
It is bright, but the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to following embodiment.It is all above-mentioned interior based on the present invention
Hold realized technology to all belong to the scope of the present invention.
Embodiment 1
It takes 0.08g to be placed in 4mL sample bottles for Buddhist nun's raw material according to Shandong, 4g isopropyl acetates is added, open Ultrasound Instrument, adjustment is super
Acoustic frequency is 20KHz, ultrasonic power 100W/mL solution, ultrasonic 20min, is made it dissolve and in supersaturated state, in 25 DEG C of conditions
Lower stirring for 24 hours, suspension is filtered, white solid is obtained, constant pressure and dry 7h obtains product at 30 DEG C.The X-ray powder of product
Diffraction pattern indicates with 2 θ, 7.3 °, 7.7 °, 8.9 °, 10.2 °, 14.6 °, 15.6 °, 17.1 °, 18.2 °, 18.9 °, 20.5 °,
There is characteristic peak at 21.2 °, 21.8 °, 22.6 °, 24.9 °, 27.0 °, 27.6 °, TGA thermogravimetric analysis is carried out to product, using Switzerland
Mei Teletuo benefit TG Α/DSC1 type thermogravimetric analyzers, atmosphere are nitrogen, and heating rate is 10 DEG C/min, and analysis result is shown in attached
Fig. 5 has apparent desolventizing peak, and it is 16.95% that desolventizing weightlessness, which compares, and product is bulk, and similar with attached drawing 2, heap density is
0.6578g/ml, angle of repose are 26.5 °.
Embodiment 2
It takes 0.24g to be placed in 20mL sample bottles for Buddhist nun's raw material according to Shandong, 14.4g isopropyl acetates is added, open Ultrasound Instrument, adjust
Whole supersonic frequency is 30KHz, ultrasonic power 200W/mL, ultrasonic 25min, makes it dissolve and is in supersaturated state, in 40 DEG C of conditions
Lower stirring 20h, suspension is filtered, and obtains white solid, and constant pressure and dry 8h obtains product at 25 DEG C.The X-ray powder of product
Diffraction pattern indicates with 2 θ, 7.3 °, 7.6 °, 8.8 °, 10.1 °, 14.5 °, 15.5 °, 17.0 °, 18.1 °, 19.0 °, 20.5 °,
There is characteristic peak at 21.2 °, 21.8 °, 22.5 °, 24.8 °, 26.9 °, 27.6 °, TGA thermogravimetric analysis is carried out to product, desolventizing loses
Again than being 17.12%, product is bulk, similar with attached drawing 2, and heap density is 0.6579g/ml, and angle of repose is 26.5 °.
Embodiment 3
Amplification test.Weigh 0.50g replaces Buddhist nun's raw material in 100mL crystallizers according to Shandong, and 28g isopropyl acetates are added, and opens
Ultrasound Instrument, adjustment supersonic frequency are 40KHz, ultrasonic power 300W/mL, ultrasonic 30min, make it dissolve and be in supersaturated state,
The use of mechanical agitation control mixing speed is 250rpm, stirs 22h under the conditions of 30 DEG C, filter, constant pressure and dry 10h is obtained at 20 DEG C
To product.The X-ray powder diffraction figure of product indicates with 2 θ, 7.3 °, 7.7 °, 8.9 °, 10.2 °, 14.4 °, 15.6 °,
There is characteristic peak at 17.2 °, 18.2 °, 18.8 °, 20.5 °, 21.2 °, 21.7 °, 22.6 °, 24.9 °, 26.9 °, 27.6 °, to product
TGA thermogravimetric analysis is carried out, it is 17.36% that desolventizing weightlessness, which compares, and product is bulk, and similar with attached drawing 2, heap density is
0.6581g/ml, angle of repose are 26 °.
Embodiment 4
It weighs 0.3g to be added in 21g isopropyl acetates for Buddhist nun's raw material according to Shandong, be stirred to clarify at 40 DEG C, with 1 DEG C/min's
Rate of temperature fall is cooled to 10 DEG C, filters, and constant pressure and dry 8h at 30 DEG C, the X-ray powder diffraction figure of product is indicated with 2 θ,
7.3°、7.8°、8.9°、10.2°、14.5°、15.5°、17.2°、18.0°、18.7°、20.4°、21.2°、21.9°、22.8°、
There is characteristic peak at 24.9 °, 26.9 °, 27.5 °, TGA thermogravimetric analysis is carried out to product, analysis result is shown in attached drawing 6, has apparent de-
Solvent peak, it is 18.15% that desolventizing weightlessness, which compares, and product is bulk, similar with attached drawing 2, and heap density is 0.6580g/ml, is stopped
Angle is 26 °.
Embodiment 5
It weighs 0.5g to be added in 40g isopropyl acetates for Buddhist nun's raw material according to Shandong, be stirred to clarify at 45 DEG C, with 5 DEG C/min's
Rate of temperature fall is cooled to 5 DEG C, filters, and constant pressure and dry 10h at 28 DEG C, the X-ray powder diffraction figure of product is indicated with 2 θ,
7.3°、7.7°、8.9°、10.2°、14.5°、15.8°、17.2°、18.2°、18.9°、20.6°、21.4°、21.8°、22.6°、
There is characteristic peak at 24.8 °, 27.0 °, 27.6 °, TGA thermogravimetric analysis is carried out to product, it is 18.20% that desolventizing weightlessness, which compares, product
Similar with attached drawing 2 for bulk, heap density is 0.6582g/ml, and angle of repose is 26 °.
Embodiment 6
It weighs 0.8g to be added in 72g isopropyl acetates for Buddhist nun's raw material according to Shandong, be stirred to clarify at 45 DEG C, with 1 DEG C/min's
Rate of temperature fall is cooled to 10 DEG C, filters, and constant pressure and dry 5h at 25 DEG C, the X-ray powder diffraction figure of product is indicated with 2 θ,
7.3°、7.7°、8.7°、10.2°、14.6°、15.6°、17.1°、18.2°、18.9°、20.5°、21.2°、21.9°、22.6°、
There is characteristic peak at 24.9 °, 26.9 °, 27.7 °, TGA thermogravimetric analysis is carried out to product, analysis result is shown in attached drawing 7, has apparent de-
Solvent peak, it is 17.74% that desolventizing weightlessness, which compares, and product is bulk, similar with attached drawing 2, and heap density is 0.6582g/ml, is stopped
Angle is 25.5 °.
Embodiment 7
It weighs 1g to be added in 85g isopropyl acetates for Buddhist nun's raw material according to Shandong, be stirred to clarify at 50 DEG C, with the drop of 2 DEG C/min
Warm rate is cooled to -10 DEG C, filters, and constant pressure and dry 7h at 25 DEG C, the X-ray powder diffraction figure of product is indicated with 2 θ,
7.3°、7.7°、8.8°、10.2°、14.6°、15.6°、17.1°、18.3°、18.9°、20.5°、21.3°、21.8°、22.6°、
There is characteristic peak at 24.8 °, 26.9 °, 27.7 °, TGA thermogravimetric analysis is carried out to product, it is 17.84% that desolventizing weightlessness, which compares, product
Similar with attached drawing 2 for bulk, heap density is 0.6584g/ml, and angle of repose is 26 °.
Claims (5)
1. a kind of replacing Buddhist nun's isopropyl acetate solvent compound according to Shandong, it is characterised in that the X- obtained using Cu-K alpha ray measurements is penetrated
The angle of diffraction that line powder diagram is indicated with 2 angles θ 7.3 ± 0.2 °, 7.7 ± 0.2 °, 8.9 ± 0.2 °, 10.2 ± 0.2 °, 14.6
±0.2°、15.6±0.2°、17.1±0.2°、18.2±0.2°、18.9±0.2°、20.5±0.2°、21.2±0.2°、21.8
There is characteristic peak at ± 0.2 °, 22.6 ± 0.2 °, 24.9 ± 0.2 °, 27.0 ± 0.2 °, 27.6 ± 0.2 °, wherein at 18.9 ± 0.2 °
The relative intensity of characteristic peak is 100%.
2. according to claim 1 replace Buddhist nun's isopropyl acetate solvent compound according to Shandong, which is characterized in that the crystal form is three
Oblique system, space group P1, cell parameter are α=81.21
(3) °, β=69.22 (3) °, γ=69.88 (3) °, unit cell volume is
3. according to claim 2 replace Buddhist nun's isopropyl acetate solvent compound according to Shandong, it is characterised in that replace Buddhist nun and second according to Shandong
The molar ratio of isopropyl propionate solvent molecule is 1:1, molecular formula C25H24N6O2·C5H10O2, the meeting before 200 DEG C in thermogravimetric analysis
There is 16.9%~18.2% weightlessness.
4. the preparation method according to claim 3 for replacing Buddhist nun's isopropyl acetate solvent compound according to Shandong, it is characterised in that logical
It crosses ultrasonic wave added constant temperature and suspends and turn brilliant preparation：According to Shandong the constant isopropyl acetate at 25 DEG C~40 DEG C of temperature will be added to for Buddhist nun's raw material
In ester solvent, it is 1 to replace the mass ratio of Buddhist nun's raw material and isopropyl acetate according to Shandong:50~60, ultrasonic wave added constant temperature, which suspends, turns the super of crystalline substance
Acoustic frequency is 20~40KHz, and ultrasonic power is 100~300W/mL solution, and ultrasonic time 20min~30min is stirred after ultrasonic
20h~for 24 hours, it filters, 7~10h of constant pressure and dry obtains replacing Buddhist nun's isopropyl acetate solvent compound according to Shandong at 20~30 DEG C.
5. the preparation method according to claim 3 for replacing Buddhist nun's isopropyl acetate solvent compound according to Shandong, it is characterised in that logical
It is prepared by the method for supercooling crystallization：It will replace Buddhist nun's dissolution of raw material in 40 DEG C~50 DEG C of isopropyl acetate solvent according to Shandong, replaced according to Shandong
The mass ratio of Buddhist nun's raw material and isopropyl acetate is 1:70~90, it is cooled to -10 DEG C with the rate of temperature fall of 1 DEG C/min~5 DEG C/min
It~10 DEG C, precipitates crystal, is obtained by filtration white solid, 5~10h of constant pressure and dry obtains described replacing Buddhist nun's acetic acid according to Shandong at 25~30 DEG C
Isopropyl ester solvated compounds.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109053738A (en) * | 2018-08-29 | 2018-12-21 | 浙江工业大学 | A kind of solvate and preparation method thereof replacing Buddhist nun according to Shandong |
| CN111138436A (en) * | 2018-11-04 | 2020-05-12 | 鲁南制药集团股份有限公司 | Ibutotinib crystal form A single crystal and preparation method thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104736178A (en) * | 2012-06-04 | 2015-06-24 | 药品循环公司 | Crystalline forms of a Bruton's tyrosine kinase inhibitor |
| CN105440040A (en) * | 2015-12-23 | 2016-03-30 | 浙江京新药业股份有限公司 | Ibrutinib purification method |
| CN105820138A (en) * | 2009-09-20 | 2016-08-03 | Abbvie 公司 | ABT-263 crystalline forms and solvates for use in treating BCL-2 protein related diseases |
| CN106008529A (en) * | 2016-08-08 | 2016-10-12 | 上海工程技术大学 | Ibrutinib solvate and preparation method thereof |
| CN106103462A (en) * | 2014-03-18 | 2016-11-09 | 赛利亚医药公司 | The new polymorphic forms of TCM B and New Solid |
| CN106117214A (en) * | 2016-06-29 | 2016-11-16 | 上海创诺医药集团有限公司 | According to Shandong for Buddhist nun's novel crystal forms and preparation method thereof |
| WO2017134588A1 (en) * | 2016-02-04 | 2017-08-10 | Shilpa Medicare Limited | Process for the preparation of ibrutinib |
| CN109053738A (en) * | 2018-08-29 | 2018-12-21 | 浙江工业大学 | A kind of solvate and preparation method thereof replacing Buddhist nun according to Shandong |
-
2018
- 2018-07-25 CN CN201810822751.XA patent/CN108727387B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105820138A (en) * | 2009-09-20 | 2016-08-03 | Abbvie 公司 | ABT-263 crystalline forms and solvates for use in treating BCL-2 protein related diseases |
| CN104736178A (en) * | 2012-06-04 | 2015-06-24 | 药品循环公司 | Crystalline forms of a Bruton's tyrosine kinase inhibitor |
| CN106103462A (en) * | 2014-03-18 | 2016-11-09 | 赛利亚医药公司 | The new polymorphic forms of TCM B and New Solid |
| CN105440040A (en) * | 2015-12-23 | 2016-03-30 | 浙江京新药业股份有限公司 | Ibrutinib purification method |
| WO2017134588A1 (en) * | 2016-02-04 | 2017-08-10 | Shilpa Medicare Limited | Process for the preparation of ibrutinib |
| CN106117214A (en) * | 2016-06-29 | 2016-11-16 | 上海创诺医药集团有限公司 | According to Shandong for Buddhist nun's novel crystal forms and preparation method thereof |
| CN106008529A (en) * | 2016-08-08 | 2016-10-12 | 上海工程技术大学 | Ibrutinib solvate and preparation method thereof |
| CN109053738A (en) * | 2018-08-29 | 2018-12-21 | 浙江工业大学 | A kind of solvate and preparation method thereof replacing Buddhist nun according to Shandong |
Non-Patent Citations (1)
| Title |
|---|
| 曾桂生等: "《砷碱渣中物质的结晶与分离》", 31 May 2016, 冶金工业出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109053738A (en) * | 2018-08-29 | 2018-12-21 | 浙江工业大学 | A kind of solvate and preparation method thereof replacing Buddhist nun according to Shandong |
| CN111138436A (en) * | 2018-11-04 | 2020-05-12 | 鲁南制药集团股份有限公司 | Ibutotinib crystal form A single crystal and preparation method thereof |
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