CN104292153B - Pyrrole Lun Panai crystal formation A and preparation method thereof - Google Patents
Pyrrole Lun Panai crystal formation A and preparation method thereof Download PDFInfo
- Publication number
- CN104292153B CN104292153B CN201410468289.XA CN201410468289A CN104292153B CN 104292153 B CN104292153 B CN 104292153B CN 201410468289 A CN201410468289 A CN 201410468289A CN 104292153 B CN104292153 B CN 104292153B
- Authority
- CN
- China
- Prior art keywords
- crystal formation
- lun panai
- pyrrole lun
- preparation
- acetic acid
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
Abstract
The present invention relates to a kind of be named as crystal formation of pyrrole Lun Panai of crystal formation A and preparation method thereof.Described crystal formation A it is characterised in that X-ray powder diffraction figure 2theta value be 7.4 ° ± 0.2 °, 9.6 ° ± 0.2 °, 19.2 ° ± 0.2 °, 17.4 ° ± 0.2 °, 15.2 ° ± 0.2 °, there is characteristic peak at 8.8 ° ± 0.2 °.This crystal formation, compared with pyrrole Lun Panai final industrialization crystal formation, improves a lot on dissolubility, and prepares this crystal formation technological operation simply, with low cost, and the optimization for this medicine following and exploitation provide important references and be worth.
Description
Technical field
The present invention relates to chemical medicine, more particularly to crystal formation of pyrrole Lun Panai and preparation method thereof.
Background technology
Pyrrole Lun Panai (compound shown in formula I) is to be researched and developed by Japanese Wei Cai company (Eisai), on December 22nd, 2012
Obtain FDA and ratify the auxiliary treatment for 12 years old age and above epileptic's partial seizures.Pyrrole Lun Panai is alpha-amido -3- hydroxyl
Base -5 methyl -4- isoxazole propanoic acid (AMPA) receptor antagonist, it passes through to suppress postsynaptic AMPA receptors glutamate activity, reduces god
It is overexcited through unit.This is the first antiepileptic with this mechanism of action of FDA approval.Its structure is as follows:
Polymorphism is widely present in medicine.The different crystal forms of same medicine are in dissolubility, fusing point, density, stable
Property etc. aspect have significant difference, thus to some extent the impact stability of medicine, homogeneity, bioavailability, curative effect and
Safety.Therefore, carry out comprehensive and systematic screening polymorph in medicament research and development, select the crystal formation being best suitable for developing, be to neglect
Depending on one of important research content.
WO2013102897A1 and disclose the anhydrous crystal forms I of pyrrole Lun Panai, anhydrous crystal forms III, anhydrous crystal forms V and anhydrous
Crystal form VII, WO2007072868 discloses the anhydrous crystal forms IV of pyrrole Lun Panai.During preparing these anhydrous crystal forms, employ third
The organic solvents such as ketone, methyl ethyl ketone, dichloromethane, methyl tertiary butyl ether(MTBE), 2- methyltetrahydrofuran, are respectively provided with certain poison
Property, different degrees of environmental pollution can be caused.
CN1942443B discloses the hydrate crystal forms of pyrrole Lun Panai, and its X-ray powder diffraction figure in 2theta value is
7.780°、8.700°、9.520°、12.450°、14.590°、15.240°、15.600°、16.180°、17.540°、19.980°、
21.040 °, 21.420 °, 23.260 °, 24.190 °, 25.440 °, 25.820 °, 26.430 °, 27.310 °, 27.860 ° and
28.870 having characteristic peak at °.
One kind that US7803818 discloses pyrrole Lun Panai is amorphous.
US7718807 discloses the hydrochlorate of pyrrole Lun Panai, hydrobromate, sulfate, mesylate, p-methyl benzenesulfonic acid
Salt, benzene sulfonate, fumarate, tartrate, succinate, benzoate.
As described above, only proposing the anhydrous crystal forms of pyrrole Lun Panai, hydrate crystal forms and salt, for other kinds of crystalline substance
Type presence or absence had both no been recorded and had no been enlightened.
The present inventor, in research process, finds that pyrrole Lun Panai also has another crystal formation, different from above-mentioned patent
Disclosed crystal formation.It is surprising that hydrate crystal forms (the patent of the final industrialization of crystal formation A and pyrrole Lun Panai of the present invention
In CN1942443B) to compare, dissolubility is improved, and prepares this crystal formation technological operation simply, with low cost, chooses solvent
Usual non-toxic, the optimization for this medicine following and exploitation provide important references and are worth.
Content of the invention
The invention provides a kind of crystal formation not being reported, hydrate (in the patent CN1942443B) phase with industrialization
Dissolubility is improved ratio, and prepares this crystal formation technological operation simply, with low cost, solvent usual non-toxic, for this medicine following
The optimization of thing and exploitation provide important references and are worth.
It is an object of the present invention to provide a kind of crystal formation of pyrrole Lun Panai, it is named as crystal formation A.
On the one hand, the crystal formation A of the pyrrole Lun Panai that the present invention provides is it is characterised in that its X-ray powder diffraction figure exists
2theta value is 7.4 ° ± 0.2 °, 9.6 ° ± 0.2 °, 19.2 ° ± 0.2 °, 17.4 ° ± 0.2 °, 15.2 ° ± 0.2 °, 8.8 ° ±
At 0.2 °, there is characteristic peak.
Further, the crystal formation A of the pyrrole Lun Panai that the present invention provides, is further characterized in that, its X-ray powder diffraction figure
2theta value be 12.0 ° ± 0.2 °, 22.9 ° ± 0.2 °, there is characteristic peak at 14.2 ° ± 0.2 °
Further, the crystal formation A of the pyrrole Lun Panai that the present invention provides, is further characterized in that, its X-ray powder diffraction figure
Basic consistent with Fig. 1.
Further, the crystal formation A of the pyrrole Lun Panai that the present invention provides is acetic acid solvate.
On the other hand, the present invention provide pyrrole Lun Panai crystal formation A it is characterised in that being heated to 30.1 DEG C, 133.4
DEG C and 173.7 DEG C nearby endothermic peak occurs, its differential scanning calorimetric thermogram is substantially consistent with Fig. 2.
On the other hand, the crystal formation A of pyrrole Lun Panai disclosed by the invention, when being heated to 135 DEG C, has about 8.3% weight
Amount loss gradient, its thermogravimetric analysis figure is substantially consistent with Fig. 3.
It is a further object to provide the preparation method of pyrrole Lun Panai crystal formation A, its preparation method includes walking as follows
Suddenly:The powder of pyrrole Lun Panai is dissolved in acetic acid and the mixed solvent system of water, passes through slow volatilization at ambient temperature, delay
The method crystallize of slow cooling, obtains crystal formation A.
Further, the mixed solvent of described acetic acid and water, the volume ratio of acetic acid and water is between 1:1 to 10:1, more excellent
Select volume ratio between 1:1 to 5:2.
It is a further object to provide a kind of pyrrole Lun Panai crystal formation A comprising effective therapeutic dose and pharmaceutic adjuvant
Pharmaceutical composition.It is usually the pyrrole Lun Panai crystal formation A of therapeutically effective amount to be mixed with one or more pharmaceutic adjuvant or contacts system
Become pharmaceutical composition or preparation, this pharmaceutical composition or preparation be known in pharmaceutical field in the way of be prepared.
In pharmaceutical composition of the present invention, pyrrole Lun Panai crystal formation A, can be used for preparing the use in antiepileptic preparation
On the way.
Beneficial effects of the present invention are:
The present invention provide crystal formation A preparation process is simple, with low cost, solvent be only acetic acid and water, safety non-toxic and
Routine is easy to get, suitable industrialized production.
The crystal formation A that the present invention provides is than the CN1942443B hydrate dissolution Du Genggao of final industrialization.Be conducive to improving
The bioavailability of medicine, the raising for curative effect of medication and safety is significant.
Brief description
Fig. 1 is the X-ray powder diffraction figure of pyrrole Lun Panai crystal formation A
Fig. 2 is the differential scanning calorimetric thermogram of pyrrole Lun Panai crystal formation A
Fig. 3 is the thermogravimetric analysis figure of pyrrole Lun Panai crystal formation A
Specific embodiment
In the present invention, used abbreviation is explained as follows:
XRPD:X-ray powder diffraction
DSC:Differential scanning calorimetric analysis
TGA:Thermogravimetric analysiss
X-ray powder diffraction figure of the present invention is adopted on Panalytical Empyrean x-ray powder diffraction instrument
Collection.The method parameter of X-ray powder diffraction of the present invention is as follows:
X ray reflection parameter:Cu,Kα
Kα11.540598;Kα21.544426
K α 2/K α 1 intensity:0.50
Voltage:45 KVs (kV)
Electric current:40 milliamperes (mA)
Divergent slit:Automatically
Scan pattern:Continuously
Sweep limitss:From 3.0 to 40.0 degree
Sampling step length:0.013 degree
Differential scanning calorimetric thermogram of the present invention gathers on TA Q2000.Differential scanning amount of the present invention
Thermoanalytical method parameter is as follows:
Temperature range:- 200 DEG C of room temperature
Sweep speed:10℃/min
Protective gas:Nitrogen 50mL/min
Thermogravimetric analysis figure of the present invention gathers on TA Q5000.The method parameter of thermogravimetric analysiss of the present invention
As follows:
Temperature range:- 300 DEG C of room temperature
Sweep speed:10℃/min
Protective gas:Nitrogen 25mL/min
Embodiment 1:
The preparation method of pyrrole Lun Panai crystal formation A:
It is 1 that the powder of 50.1mg pyrrole Lun Panai is added to 2.0mL acetic acid and water volume ratio:In 1 mixed solvent, obtain
Settled solution, at ambient temperature, suspends and stirs this solution 1 day, and centrifugation solid, after being vacuum dried 24 hours, is collected solid
Body obtains final product crystal formation A.The X-ray powder diffraction data of the crystal formation A that the present embodiment obtains is as shown in table 1.After testing its XRPD figure with
Fig. 1 is consistent, and its DSC figure is consistent with Fig. 2, and its TGA figure is consistent with Fig. 3.
The X-ray powder diffraction data of table 1 crystal formation A
2theta | D is spaced | Intensity % |
7.44 | 11.89 | 100.00 |
8.79 | 10.07 | 10.25 |
9.55 | 9.27 | 24.10 |
12.01 | 7.37 | 9.72 |
14.23 | 6.22 | 5.24 |
15.18 | 5.84 | 16.74 |
15.56 | 5.70 | 3.24 |
17.35 | 5.11 | 17.50 |
19.20 | 4.62 | 18.09 |
20.70 | 4.29 | 2.96 |
22.93 | 3.88 | 6.99 |
34.31 | 2.61 | 2.19 |
35.15 | 2.55 | 2.62 |
38.21 | 2.36 | 1.81 |
39.03 | 2.31 | 1.21 |
Embodiment 2:
The preparation method of pyrrole Lun Panai crystal formation A:
It is 5 that the powder of 10.3mg pyrrole Lun Panai is dissolved in 0.7mL acetic acid and water volume ratio:In 2 mixed solvent, obtain clear
Clear solution, this solution is heated to 50 DEG C, then slow cooling, to 5 DEG C, has solid to separate out, and after being vacuum dried 24 hours, collects solid
Body obtains final product crystal formation A.The X-ray powder diffraction data of the crystal formation A that the present embodiment obtains is as shown in table 2.
The X-ray powder diffraction data of table 2 crystal formation A
2theta | D is spaced | Intensity % |
7.43 | 11.90 | 100.00 |
8.78 | 10.07 | 16.11 |
9.54 | 9.27 | 30.15 |
12.00 | 7.38 | 9.62 |
14.23 | 6.22 | 5.86 |
15.18 | 5.84 | 20.60 |
17.33 | 5.12 | 15.66 |
19.19 | 4.62 | 15.89 |
20.84 | 4.26 | 2.05 |
22.91 | 3.88 | 6.45 |
24.29 | 3.66 | 1.86 |
34.31 | 2.61 | 1.65 |
35.14 | 2.55 | 1.79 |
38.20 | 2.36 | 1.68 |
Embodiment 3:
The preparation method of pyrrole Lun Panai crystal formation A:
It is 1 that the powder of 10.0mg pyrrole Lun Panai is added to 0.5mL acetic acid and water volume ratio:In 1 mixed solvent, obtain
Suspension solution, at ambient temperature, suspends and stirs this solution 1 day, and centrifugation solid, after being vacuum dried 12 hours, is collected solid
Body obtains final product crystal formation A.The X-ray powder diffraction data of the crystal formation A that the present embodiment obtains is as shown in table 3.
The X-ray powder diffraction data of table 3 crystal formation A
2theta | D is spaced | Intensity % |
7.46 | 11.85 | 100.00 |
8.82 | 10.03 | 17.28 |
9.57 | 9.24 | 39.80 |
12.03 | 7.35 | 11.21 |
14.29 | 6.20 | 6.83 |
15.21 | 5.82 | 24.87 |
15.58 | 5.69 | 4.06 |
17.36 | 5.11 | 22.06 |
19.21 | 4.62 | 20.94 |
20.71 | 4.29 | 2.71 |
20.98 | 4.23 | 4.44 |
22.93 | 3.88 | 8.29 |
33.05 | 2.71 | 1.71 |
34.30 | 2.61 | 2.38 |
35.14 | 2.55 | 3.06 |
38.18 | 2.36 | 2.31 |
39.04 | 2.31 | 1.41 |
Embodiment 4:
Crystal formation A and hydrate crystal forms (patent CN1942443B) dissolubility contrast experiment in water
Weigh 30mg crystal formation A and CN1942443B hydrate respectively in 12mL centrifuge tube, each addition 6mL water, capping, put
On rotary incubator, 25 revs/min are done Stirring, respectively at 1 hour, 2 hours, each sampling in 4 hours and 24 hours
1.5mL, centrifugation, filter, take clear liquid, survey its dissolubility content with high performance liquid chromatograph (HPLC).Solubility results in water
As shown in table 4.
Table 4 crystal formation A and hydrate crystal forms (CN1942443B) dissolubility comparing result in water
As shown by data, in water, crystal formation A dissolubility is superior to CN1942443B hydrate crystal forms.
Embodiment 5:
Dissolubility in simulated intestinal fluid (FeSSIF) under crystal formation A and hydrate crystal forms (patent CN1942443B) fed conditions
Contrast experiment
Weigh 30mg crystal formation A and CN1942443B hydrate respectively in 12mL centrifuge tube, respectively add 6 milliliters of FeSSIF,
Capping, is placed on rotary incubator, 25 revs/min are done Stirring, respectively at 1 hour, 2 hours, respectively takes within 4 hours and 24 hours
1.5 milliliters of sample, centrifugation, filter, take clear liquid, survey its dissolubility content with high performance liquid chromatograph (HPLC).Molten in FeSSIF
Solution degree result is as shown in table 5.
Table 5 crystal formation A and hydrate (CN1942443B) dissolubility comparing result in FeSSIF
As shown by data, in FeSSIF, crystal formation A dissolubility is superior to CN1942443B hydrate.
Claims (7)
1. a kind of acetic acid solvate crystal formation A of pyrrole Lun Panai is it is characterised in that its X-ray diffraction in figure in 2theta value is
7.4°±0.2°、9.6°±0.2°、19.2°±0.2°、17.4°±0.2°、15.2°±0.2°、8.8°±0.2°、12.0°±
0.2 °, 22.9 ° ± 0.2 °, there is characteristic peak at 14.2 ° ± 0.2 °.
2. crystal formation A according to claim 1 is it is characterised in that its X-ray powder diffraction figure is substantially consistent with Fig. 1.
3. crystal formation A according to claim 1 it is characterised in that its differential scanning calorimetric thermogram substantially with Fig. 2 mono-
Cause.
4. crystal formation A according to claim 1 is it is characterised in that its thermogravimetric analysis figure is substantially consistent with Fig. 3.
5. a kind of preparation method of the pyrrole Lun Panai crystal formation A of claim 1 is it is characterised in that solid dissolving by pyrrole Lun Panai
In the mixed solvent system of acetic acid and water, lead to the method crystallize of slow volatilization or slow cooling at ambient temperature, obtain crystalline substance
Type A.
6. preparation method according to claim 5, the volume ratio of described acetic acid and water is between 1:1 to 10:Between 1.
7. the volume ratio of preparation method according to claim 6, wherein acetic acid and water is between 1:1 to 5:Between 2.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410468289.XA CN104292153B (en) | 2013-11-26 | 2014-09-15 | Pyrrole Lun Panai crystal formation A and preparation method thereof |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310606707.2A CN103664756A (en) | 2013-11-26 | 2013-11-26 | Perampanel new type crystal A and preparation method thereof |
CN2013106067072 | 2013-11-26 | ||
CN201310606707.2 | 2013-11-26 | ||
CN201410468289.XA CN104292153B (en) | 2013-11-26 | 2014-09-15 | Pyrrole Lun Panai crystal formation A and preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104292153A CN104292153A (en) | 2015-01-21 |
CN104292153B true CN104292153B (en) | 2017-03-01 |
Family
ID=50303636
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310606707.2A Pending CN103664756A (en) | 2013-11-26 | 2013-11-26 | Perampanel new type crystal A and preparation method thereof |
CN201410468289.XA Active CN104292153B (en) | 2013-11-26 | 2014-09-15 | Pyrrole Lun Panai crystal formation A and preparation method thereof |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310606707.2A Pending CN103664756A (en) | 2013-11-26 | 2013-11-26 | Perampanel new type crystal A and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (2) | CN103664756A (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016172333A1 (en) | 2015-04-21 | 2016-10-27 | Teva Pharmaceuticals International Gmbh | A solid state form of perampanel |
CN107304183A (en) * | 2016-04-20 | 2017-10-31 | 扬子江药业集团上海海尼药业有限公司 | Pyrrole Lun Panai crystal formations and its production and use |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6949571B2 (en) * | 2000-06-12 | 2005-09-27 | Eisai Co., Ltd. | 1,2-dihydropyridine compounds, process for preparation of the same and use thereof |
MY148809A (en) * | 2004-07-06 | 2013-05-31 | Eisai R&D Man Co Ltd | Crystals of 1,2-dihydropyridine compound and their production process |
CN101304970A (en) * | 2005-12-21 | 2008-11-12 | 卫材R&D管理有限公司 | Amorphous form of 1,2-dihydropyridine compound |
US20090088574A1 (en) * | 2005-12-21 | 2009-04-02 | Eisai R&D Management Co., Ltd. | Crystal of 1,2-dihydropyridine compound (type iv) |
WO2007126060A1 (en) * | 2006-04-28 | 2007-11-08 | Eisai R & D Management Co., Ltd | Salt of 1,2-dihydropyridine compound |
EP2800747A4 (en) * | 2012-01-03 | 2015-12-09 | Mapi Pharma Ltd | Polymorphs of perampanel |
-
2013
- 2013-11-26 CN CN201310606707.2A patent/CN103664756A/en active Pending
-
2014
- 2014-09-15 CN CN201410468289.XA patent/CN104292153B/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN104292153A (en) | 2015-01-21 |
CN103664756A (en) | 2014-03-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2022088564A (en) | Process for synthesizing 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)-pyridin-3-yl)methoxy)benzaldehyde | |
EP3248983B1 (en) | Crystal form a of obeticholic acid and preparation method therefor | |
US20090209757A1 (en) | Processes for the preparation and purification of paliperidone palmitate | |
CN107848979A (en) | Pleasure is cut down for novel crystal forms of Buddhist nun's mesylate and preparation method thereof | |
KR20210054546A (en) | Salts and crystal forms of GABAA positive allosteric modulators | |
US20200157100A1 (en) | Novel salts and crystals | |
CN105111215A (en) | Crystal form and preparation method of cyclin-dependent kinase inhibitor | |
US10626135B2 (en) | Crystal forms of sodium-glucose co-transporter inhibitor, processes for preparation and use thereof | |
EP3256474B1 (en) | Ibrutinib sulphate salt | |
CN112010809A (en) | Crystal form I of olaparib and preparation method thereof | |
CN101595099B (en) | Crystalline duloxetine hydrochloride | |
CN104292153B (en) | Pyrrole Lun Panai crystal formation A and preparation method thereof | |
WO2020244349A1 (en) | Method for synthesizing furoimidazopyridine compound, polymorphic substance and polymorphic substance of salt | |
CN115427397B (en) | Crystal form of nitroquinoline prodrug, pharmaceutical composition containing crystal form, preparation method and application of pharmaceutical composition | |
US11034653B2 (en) | Crystal form of estrogen receptor inhibitor and preparation method therefor | |
CN104130207A (en) | Acotiamide hydrobromide hydrate and preparation method of crystal form thereof | |
CN111606816A (en) | Dezocine crystal form and preparation method thereof | |
CN104974146A (en) | Crystal form E and crystal form F of canagliflozin and preparation method thereof | |
CN110536888B (en) | Salt of benzopiperidine derivative, crystal form thereof, salt and preparation method of crystal form thereof | |
US10815232B2 (en) | Crystalline forms of viral-protein inhibitor drug VX-787, processes for preparation thereof and use thereof | |
TWI824626B (en) | Crystal forms of RIPK1 inhibitors and their acid salts and crystal forms of their acid salts | |
CN113135893B (en) | Benzocycloheptapyridine compounds, process for their preparation and their use | |
CN113135899B (en) | Benzocycloheptapyridine compounds, process for their preparation and their use | |
CN106794179A (en) | Novel crystal forms of Masitinib mesylate and preparation method thereof | |
CN114644615B (en) | Crystal form of indazole derivative and preparation method 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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CP01 | Change in the name or title of a patent holder |
Address after: 215123 Biological Park B4-101, No. 218 Xing Hu Street, Suzhou Industrial Park, Jiangsu Patentee after: Suzhou crystal cloud medicine Polytron Technologies Inc Address before: 215123 Biological Park B4-101, No. 218 Xing Hu Street, Suzhou Industrial Park, Jiangsu Patentee before: Crystal Pharmatech Co., Ltd. |
|
CP01 | Change in the name or title of a patent holder |