CN103694306B - A kind of method of budesonide S isomers ofthe R isomer - Google Patents
A kind of method of budesonide S isomers ofthe R isomer Download PDFInfo
- Publication number
- CN103694306B CN103694306B CN201410006875.2A CN201410006875A CN103694306B CN 103694306 B CN103694306 B CN 103694306B CN 201410006875 A CN201410006875 A CN 201410006875A CN 103694306 B CN103694306 B CN 103694306B
- Authority
- CN
- China
- Prior art keywords
- budesonide
- acetic ester
- isomer
- obtains
- add
- 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 - Fee Related
Links
- 229960004436 budesonide Drugs 0.000 title claims abstract description 44
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 title claims abstract description 42
- 238000000034 method Methods 0.000 title claims abstract description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 69
- 235000019439 ethyl acetate Nutrition 0.000 claims abstract description 23
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 13
- VOVIALXJUBGFJZ-VXKMTNQYSA-N Dexbudesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3O[C@@H](CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-VXKMTNQYSA-N 0.000 claims abstract description 12
- 229950003658 dexbudesonide Drugs 0.000 claims abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 239000007800 oxidant agent Substances 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 238000009413 insulation Methods 0.000 claims description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
- 239000012286 potassium permanganate Substances 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
- 235000019253 formic acid Nutrition 0.000 claims description 5
- 235000019441 ethanol Nutrition 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000007248 oxidative elimination reaction Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- -1 and filter Substances 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 229940117975 chromium trioxide Drugs 0.000 claims description 3
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 3
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims description 3
- 239000012065 filter cake Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 150000008065 acid anhydrides Chemical class 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- 238000007142 ring opening reaction Methods 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 3
- 230000032050 esterification Effects 0.000 abstract description 3
- 238000005886 esterification reaction Methods 0.000 abstract description 3
- 230000007062 hydrolysis Effects 0.000 abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 3
- 238000009833 condensation Methods 0.000 abstract description 2
- 230000005494 condensation Effects 0.000 abstract description 2
- 238000011084 recovery Methods 0.000 abstract description 2
- 230000009466 transformation Effects 0.000 abstract description 2
- 239000003862 glucocorticoid Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229960003957 dexamethasone Drugs 0.000 description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 3
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229960004544 cortisone Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
Abstract
The invention discloses a kind of method by budesonide S isomers ofthe R isomer, get budesonide, carry out esterification with acetic anhydride and obtain budesonide acetic ester, then under the effect of strong oxidizer, be oxidized open loop, obtain 16-α hydroxy prednisonlone acetic ester; Butyraldehyde-n and the condensation of 16-α hydroxy prednisonlone acetic ester obtain budesonide acetic ester, and hydrolysis, obtains dexbudesonide.The inventive method transformation efficiency is high, and the rate of recovery is good, effectively the S isomer of budesonide can be converted into R isomer.
Description
Technical field
The present invention relates to a kind of method utilizing budesonide S isomers ofthe high reactivity R isomer.
Background technology
Budesonide is a kind of glucocorticosteroid with efficient local anti-inflammatory effect that Sweden ABBofors researchs and develops.Budesonide, by two kinds of racemies formed with the ratio of about 1:1 with position isomer 22R and 22S of C-22 position, is locally used for the treatment of the skin caused by inflammation and allergy or respiratory symptom (as tetter, asthma and rhinitis) etc. clinically.
Dexbudesonide (R isomer) belongs to adrenal cortex hormones drug, it is the individual isomer of the budesonide C-22 position obtained by the method for chemosynthesis, 1.4 ~ 1.7 times that its local anti-inflammatory activity (rat auricle edema method) is budesonide, for 1.6 ~ 2 times of left budesonide (S isomer), be 13 times of dexamethasone; 1.5 times that local glucocorticoid effect (human vas contraction test) is budesonide, be 1.8 times of left budesonide; 2.0 times that the whole body glucocorticoid efficiency (involution of thymus test) of its subcutaneous administration is budesonide, be 6.7 times of left budesonide, be 1.7 times of dexamethasone, be 80 times of cortisone.This stronger glucocorticoid efficiency of dexbudesonide ascribes it to and glucocorticoid receptor has higher avidity, and its receptor affinity is about 1.4 times of budesonide, 11.2 times of dexamethasone, 280 times of cortisone.The budesonide now gone on the market by two kinds of racemies formed with the ratio of about 1:1 with position isomer 22R and 22S of C-22 position,
In existing document and patented method, prepare in the process of dexbudesonide and inevitably produce the left budesonide of a large amount of by products, as patent WO87/05028, WO92/11280 etc.In the method for bibliographical information, produce the S isomer of 15 ~ 20% to I haven't seen you for ages, and in refining process, have a large amount of R isomer discarded in the lump with S isomer.
Summary of the invention
The object of the invention is to overcome when to prepare dexbudesonide existing in prior art and produce a large amount of S isomer, affect the yield problem of product, a kind of method utilizing budesonide S isomers ofthe high reactivity R isomer is provided.
In order to realize foregoing invention object, the invention provides following technical scheme:
By a method for budesonide S isomers ofthe R isomer, get budesonide, carry out esterification with acetic anhydride and obtain budesonide acetic ester, formula II, then under the effect of strong oxidizer, be oxidized open loop, obtain 16-α hydroxy prednisonlone acetic ester, formula III; Butyraldehyde-n and the condensation of 16-α hydroxy prednisonlone acetic ester obtain budesonide acetic ester, formula IV, and hydrolysis, obtains dexbudesonide, formula I.
Contriver researches and develops discovery, and the R/S isomer mixture discarded can continue the raw material as preparing dexbudesonide by certain method.By recycling, improve the rate of utilization of raw material, reducing cost, and to environmental benefits.
Further, the esterification of budesonide is carried out in aprotic polar solvent.Preferably, one of following solvent or mixture is selected: methylene dichloride, chloroform, more preferably methylene dichloride.
Further, oxidative cleavage, carries out ring-opening reaction with strong oxidizer, and described strong oxidizer is selected from one of potassium permanganate, potassium bichromate, chromium trioxide or mixture.Preferably, oxidative cleavage low mass molecule alcohol, as solvent, adds Catalyzed by Formic Acid reaction.
Further, the method for budesonide S isomers ofthe R isomer, concrete operations are as follows: get the main mixing budesonide containing S-budesonide reclaimed in budesonide production process, be dissolved in methylene dichloride, be cooled to less than 0 DEG C, drip acetic anhydride, insulation reaction 10 ~ 60 minutes; Add the unreacted acid anhydrides of sodium bicarbonate aqueous solution washing removing, layering, organic layer is evaporated to dry, obtains budesonide acetic ester.
Then, budesonide acetic ester is dissolved in methyl alcohol, adds formic acid, and dissolve completely, be cooled to 5-13 DEG C, drip potassium permanganate solution, insulation reaction 1 ~ 2 is little, collecting by filtration filtrate, is concentrated into dry, obtains 16-α hydroxy prednisonlone acetic ester.
Using perchloric acid as solvent, nitrogen protection ,-30 ~-10 DEG C add butyraldehyde-n, are mixed, and add 16-α hydroxy prednisonlone acetic ester, insulation reaction 1 ~ 4 hour, after completion of the reaction, adds water, and filter, filter cake ethyl alcohol recrystallization, obtains dexbudesonide.
Compared with prior art, beneficial effect of the present invention: the inventive method transformation efficiency is high, the rate of recovery is good, effectively the S isomer of budesonide can be converted into R isomer.
Embodiment
Below in conjunction with test example and embodiment, the present invention is described in further detail.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following embodiment, all technology realized based on content of the present invention all belong to scope of the present invention.Per-cent not specified in the present invention is all weight percentage.
Embodiment 1
Drop in a kettle. and reclaim budesonide (R/S=20/80) 50g, add methylene dichloride 200ml, stirring and dissolving is complete.Then be cooled to 0 DEG C, drip diacetyl oxide 15ml.Drip complete insulation reaction 30 minutes.Then with sodium bicarbonate aqueous solution washing, layering.Dichloromethane layer is evaporated to dry, obtains budesonide acetic ester, formula II, yield.
Embodiment 2
Drop into the budesonide acetic ester 57g obtained in embodiment 1 in a kettle., add methyl alcohol 900ml, formic acid 10ml, heating for dissolving is complete.Then be cooled to 10 DEG C, drip 10% potassium permanganate solution 220ml, drip and finish, insulation reaction 1.5 hours.React completely, filter, filtrate reduced in volume, to dry, obtains 16-α hydroxy prednisonlone acetic ester, formula III, yield 85%.
Use potassium bichromate, chromium trioxide to replace potassium permanganate respectively, at identical conditions, carry out oxidative cleavage, yield is respectively 76% simultaneously, and 81%.
Embodiment 3
Drop into perchloric acid 600ml in a kettle., logical nitrogen, stirs.Be cooled to-20 DEG C and add butyraldehyde-n 23ml, then keep temperature to add the budesonide intermediate 48.7g obtained in embodiment 2.Insulation reaction 3 hours.React completely, poured into by reaction solution in 5L water, filter, filter cake ethyl alcohol recrystallization, obtains dexbudesonide acetic ester 32.4g, yield 64.8%.
R isomer: 99.2%
S isomer: 0.8%
Embodiment 4
According to patent WO92/11280 method, the hydrolysis of dexbudesonide acetic ester obtains dexbudesonide, yield 92.4%.
R isomer: 99.2%
S isomer: 0.8%
Embodiment 5
Drop into the budesonide acetic ester 50g obtained in embodiment 1 in a kettle., add methyl alcohol 900ml, formic acid 10ml, heating for dissolving is complete.Then be cooled to 10 DEG C, drip 20% potassium permanganate solution 200ml, drip and finish, insulation reaction 1.5 hours.React completely, filter, filtrate reduced in volume, to dry, obtains 16-α hydroxy prednisonlone acetic ester, formula III.
Claims (1)
1., by a method for budesonide S isomers ofthe R isomer, it is characterized in that,
Get the main mixing budesonide containing S-budesonide reclaimed in budesonide production process, be dissolved in methylene dichloride, be cooled to less than 0 DEG C, drip acetic anhydride, insulation reaction 10 ~ 60 minutes; Add the unreacted acid anhydrides of sodium bicarbonate aqueous solution washing removing, layering, organic layer is evaporated to dry, obtains budesonide acetic ester, formula II,
Budesonide acetic ester is dissolved in methyl alcohol, adds formic acid, dissolve completely, be cooled to 5-13 DEG C, drip strong oxidizer, insulation reaction oxidation open loop in 1 ~ 2 hour, collecting by filtration filtrate, is concentrated into dry, obtains 16-α hydroxy prednisonlone acetic ester, formula III;
Using perchloric acid as solvent, nitrogen protection ,-30 ~-10 DEG C add butyraldehyde-n, are mixed, and add 16-α hydroxy prednisonlone acetic ester, insulation reaction 1 ~ 4 hour, after completion of the reaction, adds water, and filter, filter cake ethyl alcohol recrystallization, obtains dexbudesonide, formula I;
Oxidative cleavage, carries out ring-opening reaction with strong oxidizer, and described strong oxidizer is selected from one of potassium permanganate, potassium bichromate, chromium trioxide or mixture
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410006875.2A CN103694306B (en) | 2014-01-07 | 2014-01-07 | A kind of method of budesonide S isomers ofthe R isomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410006875.2A CN103694306B (en) | 2014-01-07 | 2014-01-07 | A kind of method of budesonide S isomers ofthe R isomer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103694306A CN103694306A (en) | 2014-04-02 |
| CN103694306B true CN103694306B (en) | 2016-03-23 |
Family
ID=50355991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410006875.2A Expired - Fee Related CN103694306B (en) | 2014-01-07 | 2014-01-07 | A kind of method of budesonide S isomers ofthe R isomer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103694306B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105111273B (en) * | 2015-08-28 | 2017-10-27 | 湖南玉新药业有限公司 | The preparation method of budesonide |
| CN109575095A (en) * | 2019-01-20 | 2019-04-05 | 湖南科瑞生物制药股份有限公司 | A kind of preparation method of 16a- hydroxacetic acid prednisolone |
| CN109734763A (en) * | 2019-01-20 | 2019-05-10 | 湖南科瑞生物制药股份有限公司 | A kind of preparation method of 16a- hydroxacetic acid prednisolone product |
| CN109575097A (en) * | 2019-01-20 | 2019-04-05 | 湖南科瑞生物制药股份有限公司 | A kind of new preparation method of 16a- hydroxy prednisonlone product |
| CN109651474A (en) * | 2019-01-20 | 2019-04-19 | 湖南科瑞生物制药股份有限公司 | A kind of new preparation method of 16a- hydroxy prednisonlone |
| CN115785188A (en) * | 2022-12-20 | 2023-03-14 | 湖南醇健制药科技有限公司 | Preparation method of budesonide |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2990401A (en) * | 1958-06-18 | 1961-06-27 | American Cyanamid Co | 11-substituted 16alpha, 17alpha-substituted methylenedioxy steroids |
| WO1992011280A1 (en) * | 1990-12-20 | 1992-07-09 | Instytut Farmaceutyczny | Method of obtaining (22r) diastereoisomer of budesonide |
| CN102099368A (en) * | 2007-12-21 | 2011-06-15 | 先灵公司 | C-21 thioethers as glucocorticoid receptor agonists |
-
2014
- 2014-01-07 CN CN201410006875.2A patent/CN103694306B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2990401A (en) * | 1958-06-18 | 1961-06-27 | American Cyanamid Co | 11-substituted 16alpha, 17alpha-substituted methylenedioxy steroids |
| WO1992011280A1 (en) * | 1990-12-20 | 1992-07-09 | Instytut Farmaceutyczny | Method of obtaining (22r) diastereoisomer of budesonide |
| CN102099368A (en) * | 2007-12-21 | 2011-06-15 | 先灵公司 | C-21 thioethers as glucocorticoid receptor agonists |
Non-Patent Citations (1)
| Title |
|---|
| 16a,17a一二羟基甾体缩醛反应的立体选择性研究;徐黎颖;《中国优秀博硕士学位论文全文数据库 (硕士) 医药卫生科技辑》;20060715(第2006年第7期);第19页2.3.1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103694306A (en) | 2014-04-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103694306B (en) | A kind of method of budesonide S isomers ofthe R isomer | |
| Fieser et al. | Selective oxidation with N-bromosuccinimide. I. Cholic acid | |
| CN103724396A (en) | Preparation method of R-budesonide | |
| CN103910775A (en) | Synthesis method of 17alpha-hydroxyl progesterone | |
| CN104109183A (en) | New technique for synthesizing progesterone | |
| CN102603843B (en) | Preparation method of dexamethasone intermediate | |
| CN103497230A (en) | Method of preparing high-purity tanshinone IIA sodium sulfonate | |
| WO2009146619A1 (en) | A method for producing betulinic acid | |
| CN103804453B (en) | The method preparing ursodesoxycholic acid for raw material with Fel Sus domestica | |
| CN104086619B (en) | The preparation method of danazol | |
| CN105017365A (en) | Method for synthesizing 6-methyl-17alpha- hydroxyl-19-nor-pregnene-4,6-diene-3,20-diketone | |
| CN101979399A (en) | Method for producing important steroid hormone dexamethasone methyl tetraenes intermediate | |
| CN101812107B (en) | Method for synthesizing clobetasol propionate intermediate | |
| CN115611962B (en) | Method for synthesizing cholic acid | |
| CN103665078B (en) | A kind of preparation method of 17 Alpha-hydroxy steroidal esters | |
| CN115466300A (en) | Cholic acid intermediate A7 and synthesis method thereof | |
| CN114276406B (en) | Preparation method of intermediate of deoxomilpine | |
| CN114213496B (en) | Method for separating lanosterol and dihydro lanosterol | |
| CN105367618A (en) | Method for preparing hydrocortisone | |
| CN104119414A (en) | Preparation method of high-quality progesterone | |
| CN103421070A (en) | Improved pregnane alkene compound C21-acetoxylation method | |
| US20170158729A1 (en) | Method of synthesizing 25-hydroxy cholesterol | |
| CN102603844B (en) | Preparation method of betamethasone intermediate | |
| CN103923133A (en) | Method for preparing alpha-arbutin | |
| CN103665093A (en) | Preparation method of (R)-budesonide |
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 | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170518 Address after: 610041, Sichuan, Chengdu province Wuhou District 9 Bridge Street wash two district Patentee after: Chengdu Jingqin Excellent Drug Development Co.,Ltd. Address before: Science Park high tech Zone of Chengdu South Road, No. 88 610041 Sichuan province Tianfu Life Science Park building B6 No. 9 Patentee before: CHENGDU YILUKANG MEDICAL TECHNOLOGY & SERVICE Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20180309 Address after: 610000 floor, building B6, Tianfu Life Science & Technology Park, No. 88, South Park Road, high tech Zone, Sichuan, Chengdu, China Patentee after: CHENGDU YILUKANG MEDICAL TECHNOLOGY & SERVICE Co.,Ltd. Address before: 610041, Sichuan, Chengdu province Wuhou District 9 Bridge Street wash two district Patentee before: Chengdu Jingqin Excellent Drug Development Co.,Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160323 |