CN1706961A - Dexamethasone hormone medicine intermediate and its prepn process - Google Patents
Dexamethasone hormone medicine intermediate and its prepn process Download PDFInfo
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- CN1706961A CN1706961A CN 200410026220 CN200410026220A CN1706961A CN 1706961 A CN1706961 A CN 1706961A CN 200410026220 CN200410026220 CN 200410026220 CN 200410026220 A CN200410026220 A CN 200410026220A CN 1706961 A CN1706961 A CN 1706961A
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Abstract
The present invention relates to bioengineering medicine, and aims at producing dexamethasone hormone medicine intermediate in low cost and high production efficiency. The technological scheme includes preparing coarse dexamethasone acetate with diene alcohol ketone as initial material and through oxidation, fermentation, extraction, purification, dehydrogenation, pressurizing reduction, replacement and other steps; hydrolysis and purification to obtain dexamethasone product; and esterification and purification to obtain dexamethasone sodium phosphate. The present invention has low production cost and high production efficiency, and is suitable for industrial production.
Description
One, affiliated field: the present invention relates to the biotechnology medicine, particularly present clinical application is hormones bulk drug, pharmaceutical intermediate extremely widely.
Two, background technology: present domestic southern only a few manufacturer production, flow processs such as its technology all do not have open, can't contrast.The derived product methylprednisolone of dexamethasone series product belongs to the new variety of corticosteroids medicine, also be in blank at home, because corticosteroids medicine production technology is very complicated, existing fermentation process, the unit operation of chemosynthesis is with high content of technology in addition, need be through the complex reaction process in-30 steps of 20 steps, from initial feed, the average period of production reaches 4～6 months, just obtains the finished product.
Three, technology contents:
The present invention seeks to develop dexamethasone series hormonal medicaments intermediate, reduce cost, enhance productivity, and lay a solid foundation, realize the large-scale industrial production ability for production methylprednisolone, hormones bulk drug.
Technical solution of the present invention:
Dexamethasone series hormonal medicaments intermediate and technology thereof is characterized in that: the starting raw material diene alcohol ketone, become oxo bridge through hydrogen peroxide oxidation, and obtain the Wo Shi oxide compound through aluminum isopropylate, hexamethylene ketonize again; The Wo Shi thing obtains leaf mold through rhizopus niger microbiological oxidation fermentation, extraction, separation and purification, obtain the mould dehydrogen substance through the oxydehydrogenation of colter bacillus again,, obtain the tetraene product through the hydrogen and nitrogen gas pressure reduction, again through grignard reaction, connect 16 methyl, again 9.11 ethylene linkages are carried out epoxidation, obtain 1.4-diene-9 (11)-epoxy-16 2-methyl-pregnant steroid, go up iodine through 21 again, the Potassium ethanoate conversion, fluorine on the hydrofluoric acid promptly obtains first product dexamethasone acetate crude product.
First product dexamethasone acetate of above-mentioned acquisition through low temperature hydrolysis, is removed 21 acetic esters, obtain second finished product dexamethasone through refining purifying then.
Second finished product dexamethasone of above-mentioned acquisition formed sodium salt through the low temperature Phosphation, through refining purification process, obtain water miscible the 3rd product dexamethasone sodium phosphate again.
Dexamethasone series product comprises that dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate etc. are adrenal cortex hormones drugs.
Dexamethasone, the another name dexamethasone, dexamethasone, Dexamethasone, white fine crystallization powder, odorless, bitter, water insoluble, be dissolved in ethanol, acetone, ether or chloroform, fusing point 262-264 ℃.Being the hormonal medicaments with quick-acting, long-acting and potent effect, is one of preferred agents of treatment inflammation and allergic disease, and side effect is little.This series products has anti-inflammatory, antianaphylaxis, inhibition immunity, strengthens pharmacological actions such as stress reaction, toxinicide and antishock, the clinical thin yabbi sore of toxicaemia, endocrine disturbance, collagen disease, systematicness, rheumatism, autoimmune disorder, nephrotic syndrome, anaphylactic disease, asthma, inflammation, blood and the illness such as disease of hematopoietic system, various skin disease of punishing severely that are mainly used in are the indispensable first aid medicines of clinical rescue patient.Special curative effect height, the low new variety of side effect in recent years constantly occur, its clinical effect scope more and more widely, and forward is anticancer, anti-prostatic hyperplasia, clinical application field development such as antiviral, in global pharmaceutical production in occupation of consequence.
Dexamethasone series products such as dexamethasone acetate, dexamethasone, dexamethasone sodium phosphate are present clinical application corticosteroids medicines the most widely.
Advantage of the present invention and effect: by experimental results show that of short run, methylprednisolone and the dexamethasone series product produced, not only meet current in the world at present technical requirements (European Pharmacopoeia USP2000) fully in quality standard and performance index all respects, production cost of the present invention descends 3%～5%, and production efficiency increases.The scientific payoffs of this bleeding edge is laid a good foundation for realizing large-scale industrial production.
Four, specific embodiment: the starting raw material diene alcohol ketone, become oxo bridge through hydrogen peroxide oxidation, obtain the Wo Shi oxide compound through aluminum isopropylate, hexamethylene ketonize again; The Wo Shi thing obtains leaf mold through rhizopus niger microbiological oxidation fermentation, extraction, separation and purification, obtain the mould dehydrogen substance through the oxydehydrogenation of colter bacillus again,, obtain the tetraene product through the hydrogen and nitrogen gas pressure reduction, again through grignard reaction, connect 16 methyl, again 9.11 ethylene linkages are carried out epoxidation, obtain 1.4-diene-9 (11)-epoxy-16 2-methyl-pregnant steroid, go up iodine through 21 again, the Potassium ethanoate conversion, fluorine on the hydrofluoric acid promptly obtains first product dexamethasone acetate crude product.
First product dexamethasone acetate of above-mentioned acquisition through low temperature hydrolysis, is removed 21 acetic esters, obtain second finished product dexamethasone through refining purifying then.
Second finished product dexamethasone of above-mentioned acquisition formed sodium salt through the low temperature Phosphation, through refining purification process, obtain water miscible the 3rd product dexamethasone sodium phosphate again.
Dexamethasone series product comprises that dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate etc. are adrenal cortex hormones drugs.
Claims (3)
1. dexamethasone series hormonal medicaments intermediate and technology thereof is characterized in that: the starting raw material diene alcohol ketone, become oxo bridge through hydrogen peroxide oxidation, and obtain the Wo Shi oxide compound through aluminum isopropylate, hexamethylene ketonize again; The Wo Shi thing obtains leaf mold through rhizopus niger microbiological oxidation fermentation, extraction, separation and purification, obtain the mould dehydrogen substance through the oxydehydrogenation of colter bacillus again,, obtain the tetraene product through the hydrogen and nitrogen gas pressure reduction, again through grignard reaction, connect 16 methyl, again 9.11 ethylene linkages are carried out epoxidation, obtain 1.4-diene-9 (11)-epoxy-16 2-methyl-pregnant steroid, go up iodine through 21 again, the Potassium ethanoate conversion, fluorine on the hydrofluoric acid promptly obtains first product dexamethasone acetate crude product.
2. dexamethasone series hormonal medicaments intermediate according to claim 1 and technology thereof, it is characterized in that: with first product dexamethasone acetate of above-mentioned acquisition through low temperature hydrolysis, remove 21 acetic esters, obtain second finished product dexamethasone through refining purifying then.
3. dexamethasone series hormonal medicaments intermediate according to claim 2 and technology thereof, it is characterized in that: second finished product dexamethasone of above-mentioned acquisition formed sodium salt through the low temperature Phosphation, through refining purification process, obtain water miscible the 3rd product dexamethasone sodium phosphate again.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410026220 CN1706961A (en) | 2004-06-07 | 2004-06-07 | Dexamethasone hormone medicine intermediate and its prepn process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410026220 CN1706961A (en) | 2004-06-07 | 2004-06-07 | Dexamethasone hormone medicine intermediate and its prepn process |
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| Publication Number | Publication Date |
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| CN1706961A true CN1706961A (en) | 2005-12-14 |
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| CN 200410026220 Pending CN1706961A (en) | 2004-06-07 | 2004-06-07 | Dexamethasone hormone medicine intermediate and its prepn process |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103146793A (en) * | 2012-12-19 | 2013-06-12 | 广西万德药业股份有限公司 | 11-alpha hydroxylation reaction preparation method of steride hormone substance important intermediate |
| CN101696423B (en) * | 2009-10-27 | 2013-07-24 | 浙江天台药业有限公司 | Microorganism fermentation process |
| CN112094311A (en) * | 2020-10-16 | 2020-12-18 | 西安国康瑞金制药有限公司 | Process for preparing dexamethasone sodium phosphate by one-step method |
-
2004
- 2004-06-07 CN CN 200410026220 patent/CN1706961A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101696423B (en) * | 2009-10-27 | 2013-07-24 | 浙江天台药业有限公司 | Microorganism fermentation process |
| CN103146793A (en) * | 2012-12-19 | 2013-06-12 | 广西万德药业股份有限公司 | 11-alpha hydroxylation reaction preparation method of steride hormone substance important intermediate |
| CN103146793B (en) * | 2012-12-19 | 2014-07-16 | 广西万德药业股份有限公司 | 11-alpha hydroxylation reaction preparation method of steride hormone substance important intermediate |
| CN112094311A (en) * | 2020-10-16 | 2020-12-18 | 西安国康瑞金制药有限公司 | Process for preparing dexamethasone sodium phosphate by one-step method |
| CN112094311B (en) * | 2020-10-16 | 2022-04-08 | 西安国康瑞金制药有限公司 | Process for preparing dexamethasone sodium phosphate by one-step method |
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