CN103159690B - Crystallization form of symmetric macrocyclic amine compound - Google Patents
Crystallization form of symmetric macrocyclic amine compound Download PDFInfo
- Publication number
- CN103159690B CN103159690B CN201110415737.6A CN201110415737A CN103159690B CN 103159690 B CN103159690 B CN 103159690B CN 201110415737 A CN201110415737 A CN 201110415737A CN 103159690 B CN103159690 B CN 103159690B
- Authority
- CN
- China
- Prior art keywords
- nitrae
- isosorbide
- crystal form
- phenylene
- methylene
- 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
- -1 amine compound Chemical class 0.000 title abstract description 5
- 238000002425 crystallisation Methods 0.000 title abstract 4
- 230000008025 crystallization Effects 0.000 title abstract 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 7
- 210000000130 stem cell Anatomy 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 claims description 52
- 239000013078 crystal Substances 0.000 claims description 31
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 239000007787 solid Substances 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 9
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 8
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 claims description 7
- 229960002169 plerixafor Drugs 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 6
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 3
- 238000005259 measurement Methods 0.000 claims description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
- 229910052802 copper Inorganic materials 0.000 claims 1
- 239000010949 copper Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000000556 agonist Substances 0.000 abstract description 2
- 238000002411 thermogravimetry Methods 0.000 description 9
- 238000000113 differential scanning calorimetry Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000013112 stability test Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000011476 stem cell transplantation Methods 0.000 description 2
- 0 C(c1ccc(CN2CCNCCCNCCNCCC2)cc1)N1CCNCCC*CCNCCC1 Chemical compound C(c1ccc(CN2CCNCCCNCCNCCC2)cc1)N1CCNCCC*CCNCCC1 0.000 description 1
- 101100223811 Caenorhabditis elegans dsc-1 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102100021202 Desmocollin-1 Human genes 0.000 description 1
- 101000968043 Homo sapiens Desmocollin-1 Proteins 0.000 description 1
- 101000880960 Homo sapiens Desmocollin-3 Proteins 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a crystallization form of a symmetric macrocyclic amine compound which can be used as a stem cell agonist. The invention also relates to a pharmaceutical composition comprising the crystallization compound, and a method for preparing a crystallization form of the compound.
Description
Technical field
This invention relates to the crystal form of the large cyclic amine compound of the symmetry that can be used for stem cell agonist.The invention still further relates to the medical composition comprising described crystalline compounds, and can be used for the method preparing described compound crystal form.
Background technology
Symmetrical large cyclic amine compound (Plerixafor, 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, 8,11-tetraazacyclododecane tetradecane) treatment needs some types of cancer patient of stem cell transplantation to be a major progress.The integral part of cellular replacement therapy scheme will be become because this product is of value to patient, doctor and transplantation treatment center.In order to complete stem cell transplantation, about 2,000,000 stem cell/kg must be collected by body weight.Many patients need that 3-4 is little completes this process up to a few days.Even some patients do not transfer enough stem cell, thus can not transplant.Concerning many cancer patients, transferring stem cell is the unique hope reducing cancer or healing.
Plerixafor (Plerixafor), chemistry is by name: 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, 8,11-tetraazacyclododecane tetradecane, and its molecular structural formula is as follows:
For this compound is used as therapeutic agent effectively, needs to have can be easy to produce and have and can accept chemistry and the solid-state form of physical stability, this is conducive to the storage of crude drug and the processing stability of preparation.For the purity and the stability that strengthen the product produced, crystalline solid is generally better than amorphous forms.
Previously not yet the crystal form of formula I was reported to some extent.Therefore, need a kind of crystal form of stable formula I, it does not have hygroscopicity also can not deliquescence and show excellent heat stability.
Summary of the invention
The invention provides a kind of 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, the crystal form of 8,11-tetraazacyclododecane tetradecane.Surprisingly, found that crystal form of the present invention is being greater than at the temperature of about 200 DEG C thermally-stabilised, and when being at room temperature exposed to the RH range between 2%RH ~ 90%RH, having represented the weight being less than about 0.2% and changing.In addition,
When being at room temperature exposed to up to 90%RH relative humidity, crystal form of the present invention all can not deliquescence.
In its purposes, expect that crystal form of the present invention can be used for the medical composition for the preparation of stem cell mobilization.Therefore, about in the another aspect of its compositions, the invention provides a kind of medical composition, it comprises pharmaceutically acceptable supporting agent and 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-1, the crystal form of 4,8,11-tetraazacyclododecane tetradecane.
On the other hand, the invention provides a kind of method for the preparation of crystal form of the present invention, the method is characterized in that:
-according to the first embodiment, heat 1 under reflux, 1 '-[1,4-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, 8, the aqueous solution of 11-tetraazacyclododecane tetradecane eight hydrochlorate, regulate pH value of solution to 9.0 with sodium hydroxide solution, be quickly cooled to 0 DEG C, and after agitation by collecting by filtration gained solid.
-or according to the second embodiment, to 0-5 DEG C 1,1 '-[1,4-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, 8, in the aqueous solution of 11-tetraazacyclododecane tetradecane eight hydrochlorate, slowly dripping sodium hydroxide solution under not stopping stirring, separating out to no longer including solid, the solid obtained thus by collecting by filtration.By this solid suspension in pure water, suspension is at room temperature stirred 5-10 days, then pass through solid collected by filtration.
Accompanying drawing explanation
Fig. 1 illustrates of the present invention 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, powder x-ray diffraction (PXPD) figure of 8,11-tetraazacyclododecane tetradecane crystal form.
Fig. 2 illustrates of the present invention 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, differential scanning calorimetry (DSC) figure of 8,11-tetraazacyclododecane tetradecane crystal form.
Fig. 3 illustrates of the present invention 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, thermogravimetric analysis (TGA) figure of 8,11-tetraazacyclododecane tetradecane crystal form.
Fig. 4 illustrates of the present invention 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, dynamic moisture absorption (DMS) curve of 8,11-tetraazacyclododecane tetradecane crystal form.
Fig. 5 illustrates of the present invention 1, and 1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, 8,11-tetraazacyclododecane tetradecane crystal form such as embodiment 7 carries out the differential scanning calorimetry of stability test after 24 weeks (DSC) figure.
Fig. 6 illustrates of the present invention 1, and 1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, 8,11-tetraazacyclododecane tetradecane crystal form such as embodiment 7 carries out the thermogravimetric analysis of stability test after 24 weeks (TGA) figure.
Fig. 7 illustrates of the present invention 1, and 1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, 8,11-tetraazacyclododecane tetradecane crystal form such as embodiment 7 carries out the powder x-ray diffraction of stability test after 24 weeks (PXPD) figure.
Fig. 8 illustrates of the present invention 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, and 8,11-tetraazacyclododecane tetradecane crystal form such as embodiment 7 carries out HPLC figure when stability test starts.
Fig. 9 illustrates of the present invention 1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, and 8,11-tetraazacyclododecane tetradecane crystal form such as embodiment 7 carries out the HPLC figure of stability test after 24 weeks.
Detailed description of the invention
In embodiment below, by way of example illustrations is carried out to the present invention.It provides object and is to understand the present invention, and is not intended to and can not be interpreted as the scope of the present invention given by claim that restriction is appended by any way.
Embodiment 1:1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, the preparation of 8,11-tetraazacyclododecane tetradecane crystal form
Get 100g Plerixafor hydrochlorate (1,1 '-[1,4-phenylene two (methylene)]-two-1,4,8,11-tetraazacyclododecane tetradecane eight hydrochlorate), be dissolved in 500ml water, be heated to backflow, drip 20% sodium hydroxide and regulate pH to 9.0, this solution is cooled to 0 DEG C and stirs at temperature and spend the night.By collecting by filtration gained solid.
Embodiment 2:1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, the preparation of 8,11-tetraazacyclododecane tetradecane crystal form
Get 100g Plerixafor hydrochlorate (1,1 '-[1,4-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, 8,11-tetraazacyclododecane tetradecane eight hydrochlorate), be dissolved in 500ml water, be cooled to 0-5 DEG C, do not stop to stir lower slowly dropping 20% sodium hydroxide solution, separate out to no longer including solid, the solid obtained thus by collecting by filtration.By this solid suspension in 100ml pure water, suspension is at room temperature stirred 5-10 days, then pass through solid collected by filtration.
Embodiment 3: powder x-ray diffraction figure:
Instrument: Japanese Rigaku D/max-2550 powder x-ray diffraction
Condition determination: CuK α radiation, graphite monochromator, pipe pressure 40kV, pipe flow 150mA, 2 θ sweep limits 3-80 °, scanning speed 8 °/point, step-length 0.02 °.Slit condition: divergent slit is 1 °, limit for height slit is 10mm, and antiscatter slits is 1 °, and reception slit is 0.15mm.
1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, the crystal form of 8,11-tetraazacyclododecane tetradecane is provided by the effective rays of classifying in the following table and relative intensity (expressing with the percent of the strongest ray):
Embodiment 4: differential scanning calorimetry (DSC)
Instrument: Switzerland Mettler DSC 1 thermal analyzer
Condition determination: initial temperature is set to 30 DEG C, final temperature is set to 180 DEG C, and heating rate is set to 10K/min.
1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, the DSC collection of illustrative plates of the crystal form of 8,11-tetraazacyclododecane tetradecane is illustrated in Fig. 2.
Embodiment 5: thermogravimetric analysis (TGA)
Instrument: Switzerland Mettler TGA/DSC1 thermogravimetric analyzer
Condition determination: initial temperature is set to 30 DEG C, final temperature is set to 900 DEG C, and heating rate is set to 10K/min.
1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, the TGA collection of illustrative plates of the crystal form of 8,11-tetraazacyclododecane tetradecane is illustrated in Fig. 3.
Embodiment 6: dynamically moisture absorption evaluation
Dynamic moisture absorption (DMS) evaluation is at 25 DEG C, use large feeble QI balance SGA-100 system (VTI corp., Hialeah, FL 33016) of VTI to carry out.Using the sample of about 5-10mg, when starting to analyze, humidity being arranged on environment value.Typical DMS analyzes and is made up of three scanning: with the sweep speed of every step 5%RH relative humidity by environment RH to 2%RH, 2%RH to 90%RH, 90%RH to 5%RH.Every two minutes measurement qualities and when the sample quality of 5 continuity points keeps stablizing in 0.02%, become by RH into next value (± 5%RH).1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-Isosorbide-5-Nitrae, the DMS collection of illustrative plates of the crystal form of 8,11-tetraazacyclododecane tetradecane is illustrated in Fig. 4.
Sample represents the attached overview of reversible adsorption/desorption and is less than the weight change of 0.2% in 2% gamut to 90%RH.
Embodiment 7: solid-state stability is evaluated
Under 40 DEG C and 75%RH by crystal form sample storage of the present invention in multiple unlimited vial.At specified time interval, take out the content of representative bottle, and by DSC, TGA, PXRD and HPLC analytical chemistry purity.After storing 24 weeks, DSC (measure collection of illustrative plates after 24 weeks and see Fig. 5) or TGA (Fig. 6 was shown in by the rear collection of illustrative plates that measures in 24 weeks) collection of illustrative plates and PXRD (measure collection of illustrative plates after 24 weeks and see Fig. 7) figure detect change without any.The chemical purity of stored sample is 99.75%.HPLC during beginning setting-out and after 24 weeks analyzes collection of illustrative plates and sees Fig. 8 and Fig. 9 respectively.
Embodiment 8: pharmaceutical composition
Prepare 1000 formula containing the sterile injection powder of 24mg active component:
The compound of embodiment 1 ... ... ... ... ... ... ... ... ... ... ... ... ... 24g
Sodium chloride ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ..5.9g
Citric acid ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ..0.8g.
Claims (2)
1.1 Isosorbide-5-Nitrae-phenylene two '-[(methylene)]-two-Isosorbide-5-Nitrae, the crystal form of 8,11-tetraazacyclododecane tetradecane, it is for feature with the described peak position powder x-ray diffraction figure consistent with the peak position of figure shown in Fig. 1.
2. crystal form according to claim 1, is characterized in that it has use copper as anticathode diffractometer measurement and with interplanar distance d, Bragg angle 2 θ with the following powder x-ray diffraction figure of the relative intensity of expressing relative to the percent of the strongest ray expression.
3. prepare the method for crystal form according to claim 1, it is characterized in that getting 100g Plerixafor hydrochlorate (1,1 '-[Isosorbide-5-Nitrae-phenylene two (methylene)]-two-1,4,8,11-tetraazacyclododecane tetradecane eight hydrochlorate), be dissolved in 500ml water, be heated to backflow, drip 20% sodium hydroxide and regulate pH to 9.0, this solution is cooled to 0 DEG C and stirs at temperature and spend the night, by collecting by filtration gained solid.
4. prepare the method for crystal form according to claim 1, it is characterized in that getting 100g Plerixafor hydrochlorate (1,1 '-[1,4-phenylene two (methylene)]-two-1,4,8,11-tetraazacyclododecane tetradecane eight hydrochlorate), be dissolved in 500ml water, be cooled to 0-5 DEG C, do not stop to stir lower slowly dropping 20% sodium hydroxide solution, separate out to no longer including solid, the solid obtained thus by collecting by filtration, by this solid suspension in 100ml pure water, suspension is at room temperature stirred 5-10 days, then passes through solid collected by filtration.
5. pharmaceutical composition, comprises compound according to claim 1 as active component and one or more pharmaceutically useful inertia, non-toxic carrier.
6. pharmaceutical composition according to claim 5, for the manufacture of the medicine for stem cell mobilization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110415737.6A CN103159690B (en) | 2011-12-14 | 2011-12-14 | Crystallization form of symmetric macrocyclic amine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110415737.6A CN103159690B (en) | 2011-12-14 | 2011-12-14 | Crystallization form of symmetric macrocyclic amine compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103159690A CN103159690A (en) | 2013-06-19 |
| CN103159690B true CN103159690B (en) | 2015-03-25 |
Family
ID=48583258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110415737.6A Active CN103159690B (en) | 2011-12-14 | 2011-12-14 | Crystallization form of symmetric macrocyclic amine compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103159690B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1308617A (en) * | 1998-07-08 | 2001-08-15 | 阿诺麦德股份有限公司 | Antiviral macrocyclic compounds |
| EP0823902B1 (en) * | 1995-05-02 | 2001-10-24 | AnorMED Inc. | Process for preparing 1,1'- 1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane |
| CN101094684A (en) * | 2004-08-13 | 2007-12-26 | 阿诺麦德股份有限公司 | Chemokine combinations to mobilize progenitor/stem cells |
-
2011
- 2011-12-14 CN CN201110415737.6A patent/CN103159690B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0823902B1 (en) * | 1995-05-02 | 2001-10-24 | AnorMED Inc. | Process for preparing 1,1'- 1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane |
| CN1308617A (en) * | 1998-07-08 | 2001-08-15 | 阿诺麦德股份有限公司 | Antiviral macrocyclic compounds |
| CN101094684A (en) * | 2004-08-13 | 2007-12-26 | 阿诺麦德股份有限公司 | Chemokine combinations to mobilize progenitor/stem cells |
Non-Patent Citations (1)
| Title |
|---|
| 普乐沙福的合成工艺改进;杨尚彦等;《中国药物化学杂志》;20101231(第06期);第513页左栏6-15行 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103159690A (en) | 2013-06-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112457294B (en) | Compound serving as NaV1.8 retarder and preparation method and application thereof | |
| CN103857397B (en) | Noribogaine salt non-solvent compound | |
| ES2805534T3 (en) | 20,23-piperidinyl-5-O-mycaminosyltylonolide polymorphs | |
| ES2694675T3 (en) | Crystalline complex of 1-cyano-2- (4-cyclopropyl-benzyl) -4- (β-D-glucopyranos-1-yl) -benzene, methods for its preparation and use thereof for preparation of medicines | |
| CN110922403B (en) | Co-crystal formed by apixaban and carboxylic acid and preparation method thereof | |
| CA3060121A1 (en) | Polymorphic form of compound, preparation method and use thereof | |
| CN113527203A (en) | Novel crystal form of lenvatinib mesylate and preparation method and application thereof | |
| AU2017336889B2 (en) | Polymorphic form of kinase inhibitor compound, pharmaceutical composition containing same, and preparation method therefor and use thereof | |
| US20240199627A1 (en) | Monohydrate and crystalline forms of 6-[(3s,4s)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-tetrahydropyran-4-yl-7h-imidazo[1,5-a]pyrazin-8-one | |
| CN112142679A (en) | Gefitinib and vanillic acid eutectic methanol solvate and preparation method thereof | |
| JP2019512542A (en) | Crystalline salt form | |
| US20160046615A1 (en) | Novel Crystal Form of Dabrafenib Mesylate and Preparation Method Thereof | |
| CN103159690B (en) | Crystallization form of symmetric macrocyclic amine compound | |
| CN104961681B (en) | The rich mucate and its crystal formation for Buddhist nun of card | |
| US11820754B2 (en) | Polymorphs of an SSAO inhibitor | |
| CN108473507A (en) | The crystal form of Thienopyrimidine compound | |
| CN101347412A (en) | Amifostine trihydrate crystal lyophilized preparation and method of preparing the same | |
| CN113372331B (en) | Novel crystal form of Orientinib monohydrate | |
| WO2016150337A1 (en) | Ahu377 crystal form, preparation method and use thereof | |
| CN108264465B (en) | Dapoxetine hydrochloride monohydrate, preparation method and application thereof | |
| CN105985252B (en) | Ornithine aspartate crystal form IV and preparation method thereof | |
| CN109422723B (en) | Crystal form of intestinal 2B type sodium phosphate cotransporter inhibitor and preparation method thereof | |
| CN110804058A (en) | Novel ibrutinib crystal form and preparation method thereof | |
| CN114105888B (en) | Eutectic crystal of propylthiouracil and nutrient micromolecule with antioxidant activity and preparation method thereof | |
| CN107663193A (en) | Pazopanib hydrochloride and its production and use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| DD01 | Delivery of document by public notice |
Addressee: Zhu Jinghua Document name: Notification of Passing Examination on Formalities |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: HUNAN WUZHOUTONG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: ZHU JINGHUA Effective date: 20150608 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 102208 CHANGPING, BEIJING TO: 411228 XIANGTAN, HUNAN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20150608 Address after: 411228 Fenghuang Road, easy Town, Xiangtan County, Hunan Patentee after: HUNAN WUZHOUTONG PHARMACEUTICAL CO., LTD. Address before: 102208 Beijing city small town Changping District District 2-4-601 matrix Patentee before: Zhu Jinghua |
|
| CP03 | Change of name, title or address |
Address after: No. 219, biquantan Road, Tianyi Economic Development Zone, Xiangtan City, Hunan Province Patentee after: Hunan wuzhoutong Pharmaceutical Co., Ltd Address before: 411228 Fenghuang Road, easy Town, Xiangtan County, Hunan Patentee before: HUNAN WUZHOUTONG PHARMACEUTICAL Co.,Ltd. |
|
| CP03 | Change of name, title or address |