CN1317293C - Technique for synthesizing the exemestane - Google Patents
Technique for synthesizing the exemestane Download PDFInfo
- Publication number
- CN1317293C CN1317293C CNB021384894A CN02138489A CN1317293C CN 1317293 C CN1317293 C CN 1317293C CN B021384894 A CNB021384894 A CN B021384894A CN 02138489 A CN02138489 A CN 02138489A CN 1317293 C CN1317293 C CN 1317293C
- Authority
- CN
- China
- Prior art keywords
- exemestane
- crude product
- alkene
- diketone
- androstane
- 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.)
- Expired - Lifetime
Links
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 title claims abstract description 22
- 229960000255 exemestane Drugs 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 8
- 230000002194 synthesizing effect Effects 0.000 title abstract description 6
- 238000007670 refining Methods 0.000 claims abstract description 5
- 239000012043 crude product Substances 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 238000001953 recrystallisation Methods 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 238000000967 suction filtration Methods 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 claims description 3
- 229960005471 androstenedione Drugs 0.000 claims description 3
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 claims description 3
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical class O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000005516 engineering process Methods 0.000 description 6
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 238000006356 dehydrogenation reaction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005822 methylenation reaction Methods 0.000 description 3
- AQZMINLSVARCSL-UHFFFAOYSA-N 4-chloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile Chemical class ClC1=CC(=O)C(C#N)=C(C#N)C1=O AQZMINLSVARCSL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- VYWYYJYRVSBHJQ-UHFFFAOYSA-N 3,5-dinitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 VYWYYJYRVSBHJQ-UHFFFAOYSA-N 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- 238000003457 Shi epoxidation reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000007256 debromination reaction Methods 0.000 description 1
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Inorganic materials Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
Abstract
The present invention relates to a technique for synthesizing exemestane, which comprises the steps of synthesizing 6-methylene-and rest-4-alkene 3, 17-diketone, synthesizing crude exemestane and refining. The present invention has the advantages of simple technical line, easy raw material acquirement and high yield, and is suitable for home industrial production.
Description
Technical field
The present invention relates to a kind of synthesis technique of Exemestane.
Background technology
At present, the synthesis technique of Exemestane mainly contains following three kinds:
1. with androstane-4-alkene-3, the 17-diketone is a raw material, at methylal, heating reflux reaction was 6 hours under phosphorus oxychloride existed, and got androstane-6-methylene radical-4-alkene-3, the 17-diketone, yield 36%, again through DDQ (2,3-two chloro-5,6-dicyano-1, the 4-benzoquinones, abbreviation DDQ) dehydrogenation gets product, two step total recovery 10-20% (K-Afmen et al.Tetrahedron 20:597,1964).
The starting raw material androstane-4-alkene-3 of this technology, the 17-diketone can be made through the Wo Shi oxidation by dehydroepiandros-sterone, but this operational path total recovery is on the low side, and prediction industrialization cost is higher, and is unfavorable in producing.
2. with androstane-4-alkene-3, the 17-diketone is a raw material, behind 6 methylenations again through bromo, secondary debrominate and get (US4873223.1989)
The starting raw material of this technology is identical with technology 1, and 6-methylenation yield is higher, and is about 70%, and we once explored this route, finds bromo, and the debromination condition should not be controlled, and bromine water liquid is bigger to equipment corrosion, is unfavorable for suitability for industrialized production.
3, with 1,2-dehydrogenation Testosterone is a raw material, through 6 methylenations, and Jones reagent oxidation and get total recovery about 25% (K-Annen, Synthesis, 34,1982).
The advantage of this technology is that reaction is simple, and total recovery is than technology 1 height, but starting raw material 1,2-dehydrogenation Testosterone is domestic not to be sold, if by the traditional method preparation, certainly will increase reactions steps and production cost.
Summary of the invention
The technical problem to be solved in the present invention is exactly the not high and industrialization cost problem of higher of prior art yield.
The present invention includes 6-methylene radical-androstane-4-alkene 3, refining three steps of synthesizing, synthesizing crude product Exemestane and crude product Exemestane of 17-diketone with above-mentioned intermediate:
(1) 6-methylene radical one androstane-4-alkene 3, the synthetic of 17-diketone comprises the steps:
A. Androstenedione, the tetrahydrochysene furan food in one's mouth, dehydrated alcohol, triethyl orthoformate, tosic acid are added in the reactor successively, 40-45 ℃ of stirring reaction added tosic acid after 1 hour, reacted 1 hour;
B. add methylphenylamine, 37% formaldehyde, and kept this thermotonus 2 hours, be chilled to below 20 ℃, drip concentrated hydrochloric acid, finish, continue reaction 1 hour, be chilled to 0-5 ℃;
C. add water, restir reaction 1 hour, suction filtration is washed, and gets the 6-methylene radical-androstane-4-alkene 3 of yellow solid shape after the drying, the 17-diketone;
(2) the synthetic of Exemestane comprises the steps:
A. with 6-methylene radical-androstane-4-alkene 3,17-diketone, toluene, 3, the 5-dinitrobenzoic acid is heated to backflow;
B. add 2 in batches, 3-two chloro-5,6-dicyano-1,4-benzoquinones (DDQ) continues to reflux 5 hours, is chilled to room temperature, suction filtration;
C. filtrate is successively used 5% sodium hydroxide solution, 10% sulphuric acid soln, and solvent is reclaimed in saturated sodium bicarbonate liquid and saturated nacl aqueous solution washing, promptly gets the crude product Exemestane;
(3) the refining of crude product Exemestane comprises the steps:
A. in the Exemestane crude product, add acetone, add water 100ml again, use activated carbon decolorizing, filter;
B. behind reclaim under reduced pressure part acetone-water, separate out faint yellow solid, collect solid;
C. use the alcohol-water recrystallization, ethyl acetate-sherwood oil recrystallization is used in the gained crystallization once more, gets white or off-white color crystalloid finished product Exemestane.
Operational path of the present invention is simple, and raw material is easy to get, and the yield height is fit to domestic industry production.
Be process flow sheet of the present invention below:
Embodiment
L, 6-methylene radical-androstane-4-alkene 3,17-diketone synthetic
Androstenedione 40g (0.14mol), tetrahydrofuran (THF) 260ml, dehydrated alcohol 40ml, triethyl orthoformate 40ml (0.24mol), tosic acid 1.04g (6.04mmol), add in the reactor successively, 40-45 ℃ adds tosic acid 1.04g after stirring reaction l hour, reacts 1 hour, adds methylphenylamine 15.6ml (0.14mol) subsequently, 37% formaldehyde 18ml (0.22mol), and kept this thermotonus 2 hours, and be chilled to below 20 ℃, drip concentrated hydrochloric acid 100ml, finish, continue reaction l hour, be chilled to 0-5 ℃, add water 700ml, restir reaction 1 hour, suction filtration, washing gets yellow solid 28.6g after the drying, yield 68.6%, m.p.159-162 ℃ (literature value 160-163 ℃)
2, Exemestane is synthetic
6-methylene radical-androstane-4-alkene 3,17-diketone 40g (0.13mol), toluene 1600ml, 3,5-dinitrobenzoic acid 20g is heated to backflow, add DDQ 60g (0.26mol) in batches, continue to reflux 5 hours, be chilled to room temperature, suction filtration, filtrate are successively used 5% sodium hydroxide solution, 10% sulphuric acid soln, saturated sodium bicarbonate liquid and saturated nacl aqueous solution washing, reclaim solvent, get crude product 21.3g, yield 53.6%.
3, product is refining:
Crude product 21.3g adds acetone 240ml and makes moltenly, adds water 100ml, activated carbon decolorizing, filter, behind reclaim under reduced pressure part acetone one water, separate out faint yellow solid, collect solid, with alcohol-water (1: 1) recrystallization, ethyl acetate-sherwood oil (1: 1) recrystallization is used in the gained crystallization once more, gets white or off-white color crystallization 16.2g, recrystallization yield 76.1%, m.p.193 ℃.
Simultaneously, we have carried out high performance liquid chromatography (HPLC) analysis to the sample purity before and after the recrystallization: content in crude product is about 97.4%, recrystallization content and is about 98.5%, and finished product content is about 99.6%.
Claims (1)
1, a kind of synthesis technique of Exemestane comprises 6-methylene radical-androstane-4-alkene 3, the 17-diketone synthetic, synthesize three steps made from extra care of crude product Exemestane and crude product Exemestane with above-mentioned intermediate, it is characterized in that:
(1) 6-methylene radical-androstane-4-alkene 3, the synthetic of 17-diketone comprises the steps:
A. Androstenedione, tetrahydrofuran (THF), dehydrated alcohol, triethyl orthoformate, tosic acid are added in the reactor successively, 40-45 ℃ of stirring reaction added tosic acid after 1 hour, reacted 1 hour;
B. add methylphenylamine, 37% formaldehyde, and kept this thermotonus 2 hours, be chilled to below 20 ℃, drip concentrated hydrochloric acid, finish, continue reaction 1 hour, be chilled to 0-5 ℃;
C. add water, restir reaction 1 hour, suction filtration is washed, and gets the 6-methylene radical-androstane-4-alkene 3 of yellow solid shape after the drying, the 17-diketone;
(2) the synthetic of Exemestane comprises the steps:
A. with 6-methylene radical-androstane-4-alkene 3,17-diketone, toluene, 3, the 5-dinitrobenzoic acid is heated to backflow;
B. add 2 in batches, 3-two chloro-5,6-dicyano-1, the 4-benzoquinones continues to reflux 5 hours, is chilled to room temperature, suction filtration;
C. filtrate is successively used 5%NaOH solution, 10%H
2SO
4Solution, saturated NaHCO
3Liquid and saturated NaCl solution washing reclaim solvent, promptly get the crude product Exemestane;
(3) the refining of crude product Exemestane comprises the steps:
A. in the Exemestane crude product, add acetone, add water again, use activated carbon decolorizing, filter;
B. behind reclaim under reduced pressure part acetone-water, separate out faint yellow solid, collect solid;
C. use the alcohol-water recrystallization, ethyl acetate-sherwood oil recrystallization is used in the gained crystallization once more, gets white or off-white color crystalloid finished product Exemestane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021384894A CN1317293C (en) | 2002-10-24 | 2002-10-24 | Technique for synthesizing the exemestane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021384894A CN1317293C (en) | 2002-10-24 | 2002-10-24 | Technique for synthesizing the exemestane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1415624A CN1415624A (en) | 2003-05-07 |
| CN1317293C true CN1317293C (en) | 2007-05-23 |
Family
ID=4749515
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021384894A Expired - Lifetime CN1317293C (en) | 2002-10-24 | 2002-10-24 | Technique for synthesizing the exemestane |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1317293C (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080275259A1 (en) * | 2007-05-04 | 2008-11-06 | Scinopharm Taiwan, Ltd | Process for preparing aromatase inhibitors |
| WO2009002510A2 (en) * | 2007-06-25 | 2008-12-31 | Scinopharm Taiwan Ltd. | Crystalline polymorph of exemestane |
| WO2010076811A2 (en) * | 2008-12-30 | 2010-07-08 | Ind-Swift Laboratories Limited | Process for the preparation of exemestane |
| CN103360449B (en) * | 2013-07-24 | 2015-03-25 | 江苏久吾高科技股份有限公司 | Method for extracting androstenedione by use of membrane method |
| CN105407499B (en) * | 2015-10-26 | 2019-01-15 | 珠海格力电器股份有限公司 | Information processing method, device and electronic equipment |
| CN106243179B (en) * | 2016-07-31 | 2018-09-11 | 南京臣功制药股份有限公司 | A kind of Exemestane industrialized preparing process |
| CN112409432B (en) * | 2020-11-16 | 2023-07-07 | 陕西理工大学 | Synthesis method of exemestane |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4808616A (en) * | 1985-07-09 | 1989-02-28 | Farmitalia Carlo Erba S.R.L. | 6-substituted androsta-1,4-diene-3,17-diones |
| US4990635A (en) * | 1988-01-26 | 1991-02-05 | Farmitalia Carlo Erba S.R.L. | Synthesis of 6-methylene derivatives of androsta-1,4-diene-3,17-dione |
-
2002
- 2002-10-24 CN CNB021384894A patent/CN1317293C/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4808616A (en) * | 1985-07-09 | 1989-02-28 | Farmitalia Carlo Erba S.R.L. | 6-substituted androsta-1,4-diene-3,17-diones |
| US4990635A (en) * | 1988-01-26 | 1991-02-05 | Farmitalia Carlo Erba S.R.L. | Synthesis of 6-methylene derivatives of androsta-1,4-diene-3,17-dione |
Non-Patent Citations (1)
| Title |
|---|
| 依西美坦的合成 邵颖等，中国医药工业杂志，第32卷第8期 2001 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1415624A (en) | 2003-05-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101230084B (en) | Chemical synthesis method of methylprednisolone | |
| EP2360135B1 (en) | Method for manufacturing neuraminic acid derivatives | |
| CN1317293C (en) | Technique for synthesizing the exemestane | |
| CN104844593A (en) | Synthetic method for Apixaban drug intermediate | |
| CN103665084A (en) | Method for preparing abiraterone acetate | |
| CN114262278B (en) | Method for preparing oseltamivir phosphate | |
| CA1280426C (en) | 4-benzyloxy-3-pyrrolin-2-on-1-yl acetamide, its production and use | |
| CN111018928B (en) | Synthetic method and application of gastrodin hemihydrate | |
| JP4226681B2 (en) | Method for producing pyridinium compound and compound therefor | |
| CN1323071C (en) | Process for the production of 9-cis retinoic acid. | |
| CN109942397B (en) | Preparation method of royal jelly acid | |
| WO2019159871A1 (en) | Production method for cyclopentenone derivative | |
| US5008449A (en) | Method of synthesis of hydroxy-substituted-4-alkoxyphenylacetic acids | |
| JP3918120B2 (en) | Method for producing 3,7-dimethyl-2,6-octadiene-4-olide | |
| CN113773223B (en) | Method for purifying 2-amino-4-acetamino anisole by precipitation method | |
| JP3638644B2 (en) | Method for producing optically active chroman compound | |
| CN115677639B (en) | Preparation method of tetrahydro-3-oxo-2H-pyran-4-carboxylic acid methyl ester intermediate | |
| CN110452097B (en) | Preparation method of 1-hydroxypyrene | |
| CN1019484B (en) | Synthesizing 4,4' diphenyl ether diformic acid from p-nitrophenyl formic acid | |
| JP2008511582A (en) | Process for producing [2- (4-fluoro-benzyl) -phenyl] -acetic acid | |
| CN117903218A (en) | Preparation method of neohesperidin | |
| CH636850A5 (en) | PROCEDURE FOR THE MANUFACTURE OF D, 1-BETA-BENZOYLAMINE-ISOBUTYRIC ACID. | |
| CN106749053B (en) | The preparation method of Lormetazepam rearrangement product | |
| CN1148354C (en) | Process for synthesizing (imidazole-1-radical) acetic acid derivative | |
| CN1122325A (en) | Process for production of phenyllatic acid derivative |
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: NANJING CHANG AO PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: CHANG'AO PHARMACY TECHNOLOGY CO., LTD., NANJING CITY Effective date: 20081031 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20081031 Address after: No. eight hundred, No. 2, Liuhe District, Jiangsu, Nanjing Patentee after: CHANG'AO PHARMACEUTICAL TECHNOLOGY (HOLDINGS) LTD. Address before: Jiangsu province Nanjing city Qinhuai District dajiaochang No. 30 Patentee before: NANJING CHANGAO PHARMACEUTICAL SCIENCE & TECHNOLOGY Co.,Ltd. |
|
| C56 | Change in the name or address of the patentee | ||
| CP02 | Change in the address of a patent holder |
Address after: Kexinlu Liuhe District of Nanjing City, Jiangsu Province, No. 63 211500 Patentee after: CHANG'AO PHARMACEUTICAL TECHNOLOGY (HOLDINGS) LTD. Address before: 211500 No. eight hundred, No. 2, Liuhe District, Jiangsu, Nanjing Patentee before: CHANG'AO PHARMACEUTICAL TECHNOLOGY (HOLDINGS) LTD. |
|
| CP02 | Change in the address of a patent holder |
Address after: No. 63 Kexin Road, Jiangbei New District, Nanjing City, Jiangsu Province, 210000 Patentee after: CHANG'AO PHARMACEUTICAL TECHNOLOGY (HOLDINGS) LTD. Address before: Kexinlu Liuhe District of Nanjing City, Jiangsu Province, No. 63 211500 Patentee before: CHANG'AO PHARMACEUTICAL TECHNOLOGY (HOLDINGS) LTD. |
|
| CP02 | Change in the address of a patent holder | ||
| CX01 | Expiry of patent term |
Granted publication date: 20070523 |
|
| CX01 | Expiry of patent term |