CN102070691B - Metacavir crystal form, preparation method thereof and medicinal composition containing metacavir crystal form - Google Patents
Metacavir crystal form, preparation method thereof and medicinal composition containing metacavir crystal form Download PDFInfo
- Publication number
- CN102070691B CN102070691B CN201010602866A CN201010602866A CN102070691B CN 102070691 B CN102070691 B CN 102070691B CN 201010602866 A CN201010602866 A CN 201010602866A CN 201010602866 A CN201010602866 A CN 201010602866A CN 102070691 B CN102070691 B CN 102070691B
- Authority
- CN
- China
- Prior art keywords
- crystal form
- metacavir
- mei takawei
- takawei
- preparation
- 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 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- FJAOCNGVPLTSLD-NKWVEPMBSA-N [(2s,5r)-5-(2-amino-6-methoxypurin-9-yl)oxolan-2-yl]methanol Chemical compound C1=NC=2C(OC)=NC(N)=NC=2N1[C@H]1CC[C@@H](CO)O1 FJAOCNGVPLTSLD-NKWVEPMBSA-N 0.000 title abstract 4
- 239000003814 drug Substances 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 238000002425 crystallisation Methods 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 11
- 230000008025 crystallization Effects 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 5
- 238000012360 testing method Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 3
- 208000002672 hepatitis B Diseases 0.000 abstract description 8
- 238000000634 powder X-ray diffraction Methods 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 5
- 238000001291 vacuum drying Methods 0.000 description 5
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 238000011010 flushing procedure Methods 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 2
- YKBGVTZYEHREMT-UHFFFAOYSA-N 2-amino-9-[4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 108700024845 Hepatitis B virus P Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- HDRRAMINWIWTNU-NTSWFWBYSA-N [[(2s,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1CC[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HDRRAMINWIWTNU-NTSWFWBYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 208000037890 multiple organ injury Diseases 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 229940048102 triphosphoric acid Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Images
Abstract
The invention belongs to the field of medicines, and relates to a novel specific crystal form of metacavir, and a preparation method thereof. The novel specific crystal form of metacavir is characterized by a powder X-ray diffraction map. The invention also relates to a medicinal preparation consisting of the crystal form and pharmaceutically acceptable auxiliary materials, and application of the crystal form in preparing anti-hepatitis B medicines.
Description
Technical field
The present invention relates to a kind of specific crystal formation of Mei Takawei and preparation method thereof; The pharmaceutical prepn that this crystal formation and acceptable accessories are combined into and preparation reduce in the heart rate medicine and preparation treatment or prevention angina drug in application.
Background technology
Hepatitis B (hepatitis B) is called for short hepatitis B, is caused, is the main communicable disease that also can cause multiple organ injury with the hepatic disease by hepatitis B virus (HBV).The whole world has 500,000 people of surpassing die from primary hepatocarcinoma every year, and wherein nearly 80% primary hepatocarcinoma cause by chronic viral hepatitis B.In 400,000,000 chronic viral hepatitis B patients, have 75% to live in the Asia, and China is the highest country of hepatitis B sickness rate.Latest data shows, China every year because of the dead number of hepatopathy near 500,000, the loss that causes to society is up to 1,000 hundred million yuan.
Mei Takawei (6-methocy bideoxy bideoxy guanosine) is a kind of hepatitis B virus resisting nucleoside medicine of novelty, and by Chang'ao Pharmacy technology Co., Ltd., Nanjing city's research and development, its structural formula is following:
Mei Takawei is 2, the verivate of 3-dideoxyguanosine, and 2, in the 3-dideoxyguanosine class medicine, base is all existing list marketing of the medicine of VITAMIN B4, uridylic and cytosine(Cyt), not having base only is the ddG class medicine listing of guanine.Mainly owing to the physico-chemical property of ddG, ddG's is water-soluble very poor for this, extremely unstable to temperature, generally needs-20 ℃ of preservations, also is easy in vivo be degraded, so be difficult to become a kind of medicine.And Mei Takawei then has the metastable characteristics of temperature as the verivate of ddG, and while degraded in vivo is also gentle a lot of than ddG, and drug effect is suitable with lamivudine.Therefore Mei Takawei has than ddG good water solubility and more stable characteristics.
Mei Takawei is as nucleoside medicine; As the prodrug of ddG, metabolism is 2 rapidly in blood plasma, 3-dideoxyguanosine (ddG); Then in cell, be phosphorylated to active triphosphate ddGTP; Through combining to suppress duplicating of DNA, cause the synthetic termination of DNA chain, thereby suppress the protein translation and the dna replication dna of virus with the natural substrate triphosphoric acid NSC 22837 competition of HBV polymerase.Mei Takawei has overcome the defective of interferons curative effect of medication with general tolerance difference, and " resistance " problem of nucleoside medicine long-term treatment and " drug withdrawal knock-on " phenomenon, will become the new force on the anti-hbv drug market.
One Chinese patent application CN101220071 discloses a kind of crystal formation of Mei Takawei.Document (J.Org.Chem.1995,60 (24), 7902-7908) disclose through the water recrystallization and obtained the Mei Takawei solid, but do not disclosed crystal formation.
The inventor is in the crystal formation research process of Mei Takawei; Found the specific crystal formation of a kind of new Mei Takawei unexpectedly, it is different from water is the crystal formation that recrystallization solvent obtains, and it is in the preparation process; Recrystallization is few with the solvent usage quantity; Yield is high, and good stability is more suitable in pharmaceutical industry production and use.
Summary of the invention
The purpose of this invention is to provide the specific crystal formation of a kind of Mei Takawei, and this specific crystal formation is applied to be used for the preparation of anti-hbv drug in the preparation of pharmaceutical composition.
Specifically, the new crystal formation of Mei Takawei involved in the present invention is characterized in that following powder X-ray-diffractogram, and wherein the instrument of test use is the ARL-9800X x ray diffractometer x, and the target type is Cu:
Preparation side's method of Mei Takawei crystal formation of the present invention is characterized in that in ethanol, adding Mei Takawei, is heated to dissolving fully, and 10-20 ℃ leaves standstill, and crystallization filters, washing, and dry.Dwell temperature is preferably 15 ℃.
According in the crystallization method of the present invention, can use the Mei Takawei that obtains by any method, for example by document (J.Org.Chem.1995,60 (24), the Mei Takawei that the preparation method described in 7902-7908) obtains.
At the Mei Takawei of existing bibliographical information, its purification process obtains for the water recrystallization, and the inventor finds; With water is recrystallization; Comprise temperature at various crystallization conditions, under the speed of separating out etc., the crystalline powder X-ray-diffractogram of separating out is all disclosed consistent with one Chinese patent application CN101220071.
The invention still further relates to pharmaceutical composition, said pharmaceutical composition comprises with the crystal formation of the Mei Takawei of gained of the present invention as activeconstituents and one or more acceptable accessories.
Described pharmaceutical composition can be used for the treatment of hepatitis B.Doses available is because of the character of disease, severity, and one footpath, administration way and patient's age body weight are and different, and the dosage of every day is at 1 to 500 milligram.In single or divided doses.
Prepare the Mei Takawei of specific crystal formation through the present invention, the recrystallization solvent amount of using when it is refining is few, and yield is high, good stability.
Description of drawings
Powder X-ray-diffractogram of the Mei Takawei that Fig. 1 embodiment 1 makes.
Powder X-ray-diffractogram of the Mei Takawei that Fig. 2 embodiment 4 makes.
Embodiment
Below with concrete embodiment technical scheme of the present invention is described, but protection scope of the present invention is not limited thereto:
Embodiment 1: the preparation of Mei Takawei
11 Ke Meitakawei (moisture 2.1%) product adds 80ml ethanol, 40 ℃ of heating for dissolving, heat filter, 15 ℃ of following crystallizations 24 hours.Filter, an amount of cold alcohol flushing, vacuum-drying, the monitoring water cut is pulverized, and gets white powder Mei Takawei 7.8 grams, moisture 2.0%.Under following experiment condition, measure powder X-ray-diffracting spectrum (Fig. 1):
The XTRA X-ray diffractometer;
Initial angle: 2 end angles: 40 step-lengths: 0.2
Sweep velocity: 10 target type: Cu
Guan Liuguan presses: 40KV 40mA slit: 2/4/0.5/0.2
Following table is powder X-ray-diffraction spectrogram data of the Mei Takawei that uses present method and make
Embodiment 2: the preparation of Mei Takawei
Add 750ml ethanol at 110 Ke Meitakawei (moisture 2.1%) product, 40 ℃ of heating for dissolving, heat filter, 12 ℃ of following crystallizations 24 hours.Filter, an amount of cold alcohol flushing, vacuum-drying, the monitoring water cut is pulverized, and gets white powder Mei Takawei 80 grams, moisture 1.8%.Its powder X-ray-diffraction spectrogram is consistent with embodiment 1.
Embodiment 3: the preparation of Mei Takawei
Add 4000ml ethanol at 550 Ke Meitakawei (moisture 2.1%) product, 40 ℃ of heating for dissolving, heat filter, 18 ℃ of following crystallizations 24 hours.Filter, an amount of cold alcohol flushing, vacuum-drying, the monitoring water cut is pulverized, and gets white powder Mei Takawei 410 grams, moisture 1.6%.Its powder X-ray-diffraction spectrogram is consistent with embodiment 1.
Embodiment 4: the comparative example
11 Ke Meitakawei (moisture 2.1%) product adds the 90ml deionized water, and 40 ℃ of heating for dissolving add gac and stir 5min, heat filter, 5 ℃ of following crystallizations 24 hours.Filter, an amount of cold purified rinse water, vacuum-drying, the monitoring water cut is pulverized, and gets white powder Mei Takawei 6.8 grams, moisture 1.8%.Powder X-ray-diffracting spectrum is seen accompanying drawing 2
Embodiment 5: the comparative example
11 Ke Meitakawei (moisture 2.1%) product adds 100ml acetone, and 40 ℃ of heating for dissolving add gac and stir 5min, heat filter, 5 ℃ of following crystallizations 24 hours.Filter, vacuum-drying gets blocks of solid Mei Takawei 4.3 grams, moisture 1.6%.
Embodiment 5: pharmaceutical composition
Be used to prepare 1000, wherein every prescription that contains 5mg activeconstituents (calculating) with S 16257-2
The compound of embodiment 1 ... ... ... ... ... ... ... ..5.2g
CMS-Na?....................................................8g
Micropowder silica gel ... ... ... ... ... ... ... ... ... 1g
Starch ... ... ... ... ... ... ... ... ... 20g
PVP?K30?...................................................5g
Magnesium stearate ... ... ... ... ... ... ... ... ... ..1g
Granulate, compressing tablet promptly gets.
Embodiment 6: proterties is investigated test
Is 30 ℃ with the Mei Takawei of embodiment 1 and embodiment 4 in temperature, and humidity is to carry out the proterties test in 60% the environment to investigate, and in the 15th, 30,60 day, takes a sample and investigates contrast, and the result is following:
This shows that the Mei Takawei that the embodiment of the invention prepares is than the Pickering that obtains with water crystallization.
Claims (5)
1. the crystal formation of Yi Zhong Mei Takawei is characterized in that following powder X-ray-diffractogram, and the instrument that test is used is the ARL-9800X x ray diffractometer x, and the target type is Cu:
2. the method for the crystal formation of a Mei Takawei who prepares claim 1 is characterized in that in ethanol, adding Mei Takawei, is heated to dissolving fully, and 10-20 ℃ leaves standstill, and crystallization filters, washing, and dry.
3. according to the preparation method of claim 2, in ethanol, add Mei Takawei, be heated to dissolving fully, 15 ℃ leave standstill, and crystallization filters, washing, and dry.
4. a pharmaceutical composition is characterized in that comprising the described Mei Takawei of claim 1 and one or more acceptable accessories.
5. the application of the described Mei Takawei of claim 1 in making anti-hbv drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010602866A CN102070691B (en) | 2010-12-22 | 2010-12-22 | Metacavir crystal form, preparation method thereof and medicinal composition containing metacavir crystal form |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010602866A CN102070691B (en) | 2010-12-22 | 2010-12-22 | Metacavir crystal form, preparation method thereof and medicinal composition containing metacavir crystal form |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102070691A CN102070691A (en) | 2011-05-25 |
| CN102070691B true CN102070691B (en) | 2012-09-19 |
Family
ID=44029468
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010602866A Active CN102070691B (en) | 2010-12-22 | 2010-12-22 | Metacavir crystal form, preparation method thereof and medicinal composition containing metacavir crystal form |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102070691B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103360448A (en) * | 2012-04-09 | 2013-10-23 | 南京长澳医药科技有限公司 | Single crystal form of metacavir ethanol solvent compound and preparation method thereof |
| CN103364498B (en) * | 2012-04-10 | 2016-12-21 | 广州一品红制药有限公司 | Biological specimen Sino-U.S. Ta Kawei and the detection method of Metabolites Concentration thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988009332A1 (en) * | 1987-05-29 | 1988-12-01 | The Wellcome Foundation Limited | Therapeutic nucleosides |
| CN1493301A (en) * | 2002-10-29 | 2004-05-05 | 刘晓宇 | Application of 6-methocy bideoxy bideoxy guanosine in preparation of antihepatitis B medicine |
| CN101220071A (en) * | 2008-01-17 | 2008-07-16 | 南京长澳医药科技有限公司 | Stable 6-methoxy-2',3'-dideoxy guanine nucleoside, method for preparing the same and medicament composition containing the same |
-
2010
- 2010-12-22 CN CN201010602866A patent/CN102070691B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988009332A1 (en) * | 1987-05-29 | 1988-12-01 | The Wellcome Foundation Limited | Therapeutic nucleosides |
| CN1493301A (en) * | 2002-10-29 | 2004-05-05 | 刘晓宇 | Application of 6-methocy bideoxy bideoxy guanosine in preparation of antihepatitis B medicine |
| CN101220071A (en) * | 2008-01-17 | 2008-07-16 | 南京长澳医药科技有限公司 | Stable 6-methoxy-2',3'-dideoxy guanine nucleoside, method for preparing the same and medicament composition containing the same |
Non-Patent Citations (1)
| Title |
|---|
| Morris J. Robins et al.《Nucleic Acid Related Compounds. 114. Synthesis of 2,6-(Disubstituted)purine 2",3"-Dideoxynucleosides and Selected Cytotoxic, Anti-Hepatitis B, and Adenosine Deaminase Substrate Activities》.《J.heterocylic Chem.》.2001,第38卷1297-1306. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102070691A (en) | 2011-05-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW201268B (en) | ||
| CN107428792A (en) | For treating the phosphamide of hepatitis type B virus | |
| WO2009026790A1 (en) | Crystal entecavir fomulation and the preparation method thereof | |
| WO2013004171A1 (en) | Use of c15-substituted andrographolide derivatives in preparation of anti-hepatitis b virus medicament | |
| CN102070691B (en) | Metacavir crystal form, preparation method thereof and medicinal composition containing metacavir crystal form | |
| CN1872853A (en) | Derivative of purine | |
| CN103058972B (en) | Phenyl C-glucoside derivatives containing cyclohexane structure as well as preparation method and application thereof | |
| CN101220071B (en) | Stable 6-methoxy-2',3'-dideoxy guanine nucleoside, method for preparing the same and medicament composition containing the same | |
| CN107540710A (en) | Liver delivers antivirus medicine nucleosides cyclic phosphate compound and application | |
| WO2014056396A1 (en) | Flumatinib mesylate crystal form and preparation method and use thereof | |
| CN101054393B (en) | Adefovir dipivoxil anhydrous crystal, preparation method and medicine composition thereof | |
| CA2044125A1 (en) | Anti-hbv pyrimidine nucleoside | |
| CN103360448A (en) | Single crystal form of metacavir ethanol solvent compound and preparation method thereof | |
| CN102485229B (en) | antiviral drugs | |
| CN101732316A (en) | Lamivudine preparation and preparation method thereof | |
| CN103845345A (en) | Hepatitis treatment medicament | |
| CN103690552A (en) | Pharmaceutical composition and application thereof to preparing pharmaceutical preparation for treating hepatitis B | |
| CN100516078C (en) | Adefovir dipivoxil CHARIOTEER crystallographic form and preparation method thereof | |
| WO2014129884A2 (en) | Composition with inhibitory effect on viral integrase activity | |
| CN107849074A (en) | A kind of alkoxyalkyl ester prodrugs of nucleoside analog and its application | |
| CN115403571B (en) | Arctigenin derivative, preparation method and application | |
| WO1999045917A1 (en) | Remedies for aids | |
| CN102643257B (en) | Preparation method for glycal | |
| CN110372765B (en) | Tenofovir derivative and preparation method and application thereof | |
| CN104644576A (en) | Telbivudine orally-disintegrating tablet 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 | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: GUANGZHOU VANKING PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: CHANG'AO SCIENCE AND TECHNOLOGY OF MEDICAL INDUSTRY CO LTD, NANJING Effective date: 20141021 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 210038 NANJING, JIANGSU PROVINCE TO: 510760 GUANGZHOU, GUANGDONG PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20141021 Address after: 510760 Guangdong city of Guangzhou province Guangzhou economic and Technological Development Zone East Road No. 6 self building Patentee after: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. Address before: 210038 Nanjing economic and Technological Development Zone, Jiangsu Province, No. Wing Road, No. 1 Patentee before: NANJING CHANGAO PHARMACEUTICAL SCIENCE & TECHNOLOGY Co.,Ltd. |
|
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Li Hanxiong Inventor after: Liu Cailian Inventor before: Liu Cailian |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221110 Address after: No.6 Dongbo Road, East District, Guangzhou Economic and Technological Development Zone, Guangdong 510000 Patentee after: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. Patentee after: GUANGDONG ZERUI PHARMACEUTICAL Co.,Ltd. Patentee after: Guangzhou Lianrui Pharmaceutical Co.,Ltd. Patentee after: Guangzhou Runlin Pharmaceutical Technology Co.,Ltd. Patentee after: Euphorbia Biological Medicine Co.,Ltd. Address before: 510760 Building 1, No.6 Dongbo Road, Guangzhou Economic and Technological Development Zone, Guangzhou City, Guangdong Province Patentee before: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221220 Address after: No.6 Dongbo Road, East District, Guangzhou Economic and Technological Development Zone, Guangdong 510000 Patentee after: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. Patentee after: GUANGDONG ZERUI PHARMACEUTICAL Co.,Ltd. Patentee after: Guangzhou Lianrui Pharmaceutical Co.,Ltd. Patentee after: Guangzhou Runlin Pharmaceutical Technology Co.,Ltd. Patentee after: Euphorbia Biological Medicine Co.,Ltd. Patentee after: Guangdong Ruishi Pharmaceutical Technology Co.,Ltd. Address before: No.6 Dongbo Road, East District, Guangzhou Economic and Technological Development Zone, Guangdong 510000 Patentee before: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. Patentee before: GUANGDONG ZERUI PHARMACEUTICAL Co.,Ltd. Patentee before: Guangzhou Lianrui Pharmaceutical Co.,Ltd. Patentee before: Guangzhou Runlin Pharmaceutical Technology Co.,Ltd. Patentee before: Euphorbia Biological Medicine Co.,Ltd. |