CN101081839B - Refining technique of famotidine raw material - Google Patents
Refining technique of famotidine raw material Download PDFInfo
- Publication number
- CN101081839B CN101081839B CN2006100517901A CN200610051790A CN101081839B CN 101081839 B CN101081839 B CN 101081839B CN 2006100517901 A CN2006100517901 A CN 2006100517901A CN 200610051790 A CN200610051790 A CN 200610051790A CN 101081839 B CN101081839 B CN 101081839B
- Authority
- CN
- China
- Prior art keywords
- famotidine
- raw material
- refining
- controlled
- solution
- 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
- 229960001596 famotidine Drugs 0.000 title claims abstract description 37
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title claims abstract description 22
- 238000007670 refining Methods 0.000 title claims abstract description 10
- 239000002994 raw material Substances 0.000 title claims description 20
- 238000010438 heat treatment Methods 0.000 claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000001291 vacuum drying Methods 0.000 claims abstract description 17
- 238000001816 cooling Methods 0.000 claims abstract description 14
- 239000000843 powder Substances 0.000 claims abstract description 13
- 238000010992 reflux Methods 0.000 claims abstract description 13
- 238000005303 weighing Methods 0.000 claims abstract description 13
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 238000005406 washing Methods 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims description 32
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 13
- 238000000967 suction filtration Methods 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 5
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 239000012535 impurity Substances 0.000 abstract description 7
- 238000005516 engineering process Methods 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract 4
- 231100000956 nontoxicity Toxicity 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 21
- 239000007864 aqueous solution Substances 0.000 description 8
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 6
- 229940005526 famotidine injection Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229940090044 injection Drugs 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000008399 tap water Substances 0.000 description 3
- 235000020679 tap water Nutrition 0.000 description 3
- 229910021642 ultra pure water Inorganic materials 0.000 description 3
- 239000012498 ultrapure water Substances 0.000 description 3
- 210000002249 digestive system Anatomy 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 101000939456 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 29 Proteins 0.000 description 1
- 206010020601 Hyperchlorhydria Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 102100029818 Ubiquitin carboxyl-terminal hydrolase 29 Human genes 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- GGWBHVILAJZWKJ-KJEVSKRMSA-N ranitidine hydrochloride Chemical compound [H+].[Cl-].[O-][N+](=O)\C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 GGWBHVILAJZWKJ-KJEVSKRMSA-N 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention belongs to the field of medicine producing technology, and is especially process of refining famotidine material. The technological scheme of the present invention is that the famotidine material refining process includes the following steps: weighing famotidine material in certain ratio, adding water solution of alcohol, heating reflux to form light orange solution, hot filtering, cooling to room temperature, cooling in cold storage room of refrigerator, suction filtering, washing and vacuum drying to obtain white powder. The present invention has the advantages of simple technological process, high safety, no toxicity and capacity of eliminating impurity from famotidine material effectively.
Description
Technical field
The invention belongs to field of medicine producing technology, particularly relate to a kind of process for purification of famotidine raw material.
Background technology
Famotidine (Famotidine) is a kind of antacid and gastric mucosal protection medicine, is one of digestive system medicine, is used for the gastric acid inhibitory secretion clinically and also can suppresses pepsic secretion.
Digestive system is one of common frequently-occurring disease of China, wherein based on Peptic Ulcers.Peptide ulceration is a kind of common chronic inflammatory disease, mainly because of hyperchlorhydria, smoking, drink, nervous, medicine irritation (as ASP, INDOMETHACIN, piroxicam etc.) and irregular diet cause.Show that according to domestic data the stomach ulcer sickness rate accounts for 10～12% of population.The huge market demand of anti-ulcerative drug, wherein H
2The share of market of-receptor antagonist〉30%.
Compare with Ranitidine HCL, Cimitidine Type A/AB, famotidine is considered to the H of effective high selectivity
2-receptor antagonist is one of best-selling medicine in the world, in the Digestive tract medicine, only come omeprazole after, sell and to be in second.Its lower price is used in China the very big market space.In recent years, famotidine has become bellwether for the class D medicine in China market.
Present domestic famotidine has tablet, capsule, the listing of formulations such as injection, but find that in clinical use there is bigger side effect in famotidine, particularly liquid drugs injection and freeze-drying famotidine, contained impurity has certain relevant in the existence of finding side effect after deliberation and the medicine, especially for intravenous formulation, for reducing the foreign matter content of injectable dosage forms, increase the security that injection famotidine formulation is used, so various countries are for the control of raw material impurity content and the strictness thereof of famotidine injection type, according to China's state-promulgated pharmacopoeia standard, the content of famotidine raw material impurity must be controlled at below 2%; According to USP standard USP29, the content of impurity must be controlled at below 1.0%; According to British Pharmacopoeia standard BP 2005, the content of impurity also is to be controlled at below 1.0%, and Japanese Pharmacopoeia JP-14 is controlled at below 0.5%.
Publication number is the world (China) the patent famotidine injection of CN1482910A, and this patent is also just studied for the famotidine injection raising stability of preparation, the content of famotidine composition and the content of impurity is not controlled.
Summary of the invention
The objective of the invention is to be to provide that a kind of technology is simple, safety non-toxic, can effectively reduce the process for refining of foreign matter content in the famotidine raw material.
Technical scheme of the present invention is to operate as follows:
Take by weighing famotidine raw material in proportion, add alcohol solution, heating refluxes, to molten entirely, solution is greenish orange look, and heat filtering stops heating, is cooled to room temperature, changes the cold compartment of refrigerator cooling over to, suction filtration, washing final vacuum drying, control drying temperature and vacuum tightness get the white or thick matter powder of off-white color.
The ratio of raw material and alcohol solution is preferably 1: 2～1: 200 (g/v).
The ratio of alcohol solution preferably is controlled at 0.1: 1～10: 1 (v/v).
The alcohol of alcohol solution is preferably one or more mixture of methyl alcohol, ethanol, ethylene glycol, Virahol, isopropylcarbinol.
Temperature preferably was controlled at 40～95 ℃ when raw material all dissolved.
The mixing solutions of cool to room temperature preferably continues to stir.
Vacuum drying temperature preferably is controlled at 30～80 ℃.
The vacuum drying time preferably was controlled at 2～10 hours.
The invention has the advantages that:
Technology is simple, safety non-toxic, can effectively reduce foreign matter content in the famotidine raw material, the foreign matter content in the famotidine raw material is controlled at below 1%, thereby begins to control incidence rate of adverse reaction from the raw material source.
Embodiment
Below in conjunction with embodiment the present invention is further described, but the present invention is not limited by embodiment.
Embodiment 1:
Method: famotidine: 10% methanol aqueous solution=1:2 (g/v)
Take by weighing this product in proportion, add 10% methanol aqueous solution, stirring heating, reflux, molten (75 ℃) extremely entirely, solution is greenish orange look, stop heating, naturally cool to room temperature, continue to stir 10hr, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration is used purified water Xian five times, and 95% methyl alcohol is washed five times, vacuum-drying, temperature
80 ℃, vacuum tightness (
-0.01MPa) dry 5 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 2:
Method: famotidine: 10% aqueous ethanolic solution=1:2 (g/v)
Take by weighing this product in proportion, add 10% aqueous ethanolic solution, stirring heating, reflux, molten (40 ℃) extremely entirely, solution is greenish orange look, stop heating, naturally cool to room temperature, continue to stir 90min, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration is used purified water Xian five times, and 95% ethanol is washed five times, vacuum-drying, temperature
30 ℃, vacuum tightness (
-1.00MPa) dry 10 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 3:
Method: famotidine: 10% aqueous glycol solution=1:10 (g/v)
Take by weighing this product in proportion, add 10% aqueous glycol solution, stirring heating, reflux, molten (60 ℃) extremely entirely, solution is greenish orange look, stop heating, be cooled to room temperature, continue to stir 100min with tap water, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration is used ultrapure water Xian five times, and 95% ethylene glycol is washed five times, vacuum-drying, temperature
60 ℃, vacuum tightness (
-0.5MPa) dry 5 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 4:
Method: famotidine: 10% isopropanol water solution=1:22 (g/v)
Take by weighing this product in proportion, add 10% isopropanol water solution, stirring heating, reflux, molten (55 ℃) stop heating extremely entirely, naturally cool to room temperature, continue to stir 180min, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration, with ultrapure water Xian five times, 95% Virahol is washed five times, vacuum-drying, temperature
70 ℃, vacuum tightness (
-0.22MPa) dry 6 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 5:
Method: famotidine: the 30% isopropylcarbinol aqueous solution=1:50 (g/v)
Take by weighing this product in proportion, add the 30% isopropylcarbinol aqueous solution, stirring heating, reflux, molten (56 ℃) stop heating extremely entirely, be cooled to room temperature with tap water, continue to stir 30min, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration, with distilled water Xian once, 95% isopropylcarbinol is washed once, vacuum-drying, temperature
40 ℃, vacuum tightness (
-0.19MPa) dry 8 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 6:
Method: famotidine: 40% methanol aqueous solution=1:80 (g/v)
Take by weighing this product in proportion, add 40% methanol aqueous solution, stirring heating refluxes, extremely entirely molten (70 ℃), stop heating, naturally cool to room temperature, continue to stir 300min, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration, with distilled water Xian three times, 95% methyl alcohol is given a baby a bath on the third day after its birth time, vacuum-drying, temperature
35 ℃, vacuum tightness (
-0.33MPa) dry 6 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 7:
Method: famotidine: 60% isopropanol water solution=1:100 (g/v)
Take by weighing this product in proportion, add 60% isopropanol water solution, stirring heating, reflux, molten (55 ℃) stop heating extremely entirely, be cooled to room temperature with tap water, continue to stir 50min, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration, steam water Xian five times with single, 95% Virahol is given a baby a bath on the third day after its birth inferior, vacuum-drying, temperature
35 ℃, vacuum tightness (
-0.4MPa) dry 8 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 8:
Method: famotidine: 90% aqueous ethanolic solution=1:5 (g/v)
Take by weighing this product in proportion, add 90% aqueous ethanolic solution, stirring heating refluxes, extremely entirely molten (45 ℃), stop heating, naturally cool to room temperature, continue to stir 180min, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration, steam water Xian three times with single, 95% ethanol is washed five times, vacuum-drying, temperature
65 ℃, vacuum tightness (
-0.6MPa) dry 6 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 9:
Method: famotidine: 90% methanol aqueous solution=1:150 (g/v)
Take by weighing this product in proportion, add 90% methanol aqueous solution, stirring heating refluxes, extremely entirely molten (90 ℃), stop heating, naturally cool to room temperature, continue to stir 210min, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration, with purified water Xian five times, 95% methyl alcohol is given a baby a bath on the third day after its birth time, vacuum-drying, temperature
55 ℃, vacuum tightness (
-0.7MPa) dry 8 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Embodiment 10:
Method: famotidine: 90% isopropanol water solution=1:200 (g/v)
Take by weighing this product in proportion, add 90% isopropanol water solution, stirring heating, reflux, molten (95 ℃) stop heating extremely entirely, naturally cool to room temperature, continue to stir 150min, change the cold compartment of refrigerator cooling over to more than 2 hours, suction filtration, with ultrapure water Xian three times, 95% Virahol is given a baby a bath on the third day after its birth inferior, vacuum-drying, temperature
75 ℃, vacuum tightness (
-0.8MPa) dry 2 hours (look particular case, middle stirring once), promptly get and be white or the thick matter powder of off-white color.
Claims (5)
1. the process for refining of a famotidine raw material is characterized in that operating as follows:
Take by weighing famotidine raw material in proportion, add alcohol solution, heating refluxes, to molten entirely, solution is greenish orange look, and heat filtering stops heating, is cooled to room temperature, changes the cold compartment of refrigerator cooling over to, suction filtration, washing final vacuum drying, control drying temperature and vacuum tightness get the white or thick matter powder of off-white color; Wherein the g/v ratio of raw material and alcohol solution is 1: 2～1: 200, and the volume ratio of alcohol solution was controlled at 0.1: 1～10: 1, and the alcohol of alcohol solution is one or more mixture of ethanol, ethylene glycol, Virahol, isopropylcarbinol.
2. the process for refining of famotidine raw material according to claim 1, temperature is controlled at 40～95 ℃ when it is characterized in that raw material all dissolves.
3. the process for refining of famotidine raw material according to claim 1 is characterized in that the mixing solutions of cool to room temperature continues to stir.
4. the process for refining of famotidine raw material according to claim 1 is characterized in that vacuum drying temperature is controlled at 30～80 ℃.
5. the process for refining of famotidine raw material according to claim 1 is characterized in that the vacuum drying time was controlled at 2～10 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100517901A CN101081839B (en) | 2006-06-02 | 2006-06-02 | Refining technique of famotidine raw material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100517901A CN101081839B (en) | 2006-06-02 | 2006-06-02 | Refining technique of famotidine raw material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101081839A CN101081839A (en) | 2007-12-05 |
| CN101081839B true CN101081839B (en) | 2010-12-29 |
Family
ID=38911661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006100517901A Active CN101081839B (en) | 2006-06-02 | 2006-06-02 | Refining technique of famotidine raw material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101081839B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1033521A (en) * | 1987-12-17 | 1989-06-28 | 马格拉·帕拉研究中心 | Novel 2-guanidine radicals thiazolium compounds and preparation method thereof, and the intermediate that is used as Famotidine pyridine preparation technology |
-
2006
- 2006-06-02 CN CN2006100517901A patent/CN101081839B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1033521A (en) * | 1987-12-17 | 1989-06-28 | 马格拉·帕拉研究中心 | Novel 2-guanidine radicals thiazolium compounds and preparation method thereof, and the intermediate that is used as Famotidine pyridine preparation technology |
Non-Patent Citations (2)
| Title |
|---|
| 戴祥荣等.法莫替丁的合成.医药工业18 6.1987,18(6),250-252. |
| 戴祥荣等.法莫替丁的合成.医药工业18 6.1987,18(6),250-252. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101081839A (en) | 2007-12-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2423122C2 (en) | Complex compounds of iron with carbohydrates | |
| CN103040064A (en) | Preparation method of self-heal, folium mori and chrysanthemum beverage | |
| WO2023088073A1 (en) | Multifunctional american ginseng hydrolyzed peptide, preparation method therefor, and application thereof | |
| CN101011397A (en) | Pantoprazole sodium freeze dried injection and preparation method thereof | |
| US20180008678A1 (en) | Preparation Method of the Albumin Peptide Combination and the Action of Inhibiting the Proliferation of Cancer Cells Thereof | |
| CN102140099A (en) | Novel pyridine derivative | |
| CN108524493A (en) | Application of the dihydromyricetin promotor composition in resisting alcoholic liver oxidative damage | |
| CN101081839B (en) | Refining technique of famotidine raw material | |
| CN1951424B (en) | Pharmaceutical composition for treating gynecological inflammation and preparation method thereof | |
| JP4516958B2 (en) | Anti-diabetic composition | |
| CN110054606B (en) | Dihydromyricetin-berberine hydrochloride pharmaceutical co-crystal and preparation method thereof | |
| JP2021515802A (en) | Rectal mucosa-administered preparation of anemoside B4 and its manufacturing method | |
| CN1044607C (en) | Medicine of alginic polysaccharide sulfate for treatment of nephrasthenia and angiopathy and preparation method thereof | |
| KR20100031069A (en) | Mastic extracts and preparation thereof | |
| CN1596893A (en) | Cimetidine freeze-dried powder-injection and its preparation method | |
| CN1883607B (en) | Pharmaceutical composition for treating gynecological inflammation and method for preparing same | |
| CN113004429A (en) | Refining method of carboxyl ferric maltose | |
| CN107595787A (en) | A kind of preparation method of the double meglumine lyophilized formulations of injection Fosaprepitant | |
| CN103820277B (en) | A kind of clearing heat and detoxicating wine of wintercherry and production method | |
| KR101400306B1 (en) | A Method for Preparing of Salt and Salt Prepared by the Method | |
| CN103059000A (en) | Novel omeprazole compound and pharmaceutical composition thereof | |
| CN101194972A (en) | Medicine for treating digestibility canker and preparations thereof | |
| CN100364505C (en) | Fengshining drop pill for treating rheumatism and its preparation method | |
| CN100375630C (en) | Compound drop pills with flavescent sophora root and its preparation method | |
| CN101492462B (en) | Benzimidazole derivative containing isoxazole-pyridine |
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: HAINAN PULIN PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: FAN MINHUA Effective date: 20110801 Owner name: ZHEJIANG RUIDA PHARMACEUTICAL CO., LTD. HANGZHOU S |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 310009 HANGZHOU, ZHEJIANG PROVINCE TO: 571127 HAIKOU, HAINAN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20110801 Address after: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Co-patentee after: Zhejiang Ruida Pharm Co.,Ltd. Patentee after: Hainan Poly Pharm Co.,Ltd. Co-patentee after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Address before: 310009, 6 building, Jintai business building, 571 Qing Jie street, Zhejiang, Hangzhou Patentee before: Fan Minhua |
|
| C56 | Change in the name or address of the patentee |
Owner name: HAINAN PLOY PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HAINAN PULIN PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Patentee after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Address before: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Patentee before: Hainan Poly Pharm Co.,Ltd. Patentee before: Zhejiang Ruida Pharm Co.,Ltd. Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. |
|
| DD01 | Delivery of document by public notice |
Addressee: Zhu Xulei Document name: It is deemed that no notice has been given |
|
| DD01 | Delivery of document by public notice | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230112 Address after: 571127 Guilin Ocean Economic Development Zone, Meilan District, Haikou City, Hainan Province Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Address before: 571127 Guilin Ocean Economic and Technological Development Zone, Meilan District, Haikou City, Hainan Province Patentee before: HAINAN POLY PHARM. Co.,Ltd. Patentee before: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Zhu Xulei Document name: Notification of Conformity |