Check patentability & draft patents in minutes with Patsnap Eureka AI!

Synthesis process of hydrocortisone hemisuccinate

A technology of hydrocortisone and succinate, applied in steroids, organic chemistry, etc., can solve the problem of triethylamine catalytic reaction activity, low selectivity, large amount of succinic anhydride and reaction solvent, pine hemisuccinic acid, etc. The problem of low ester yield is to achieve the effect of process optimization, simple post-processing operation and reduction of processing cost.

Inactive Publication Date: 2021-01-15
安徽海洋药业有限公司
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The defects that exist in several existing synthetic techniques: the one, a large amount of use of pyridine is more toxic; the other is the use of mixed solvents, which is not conducive to solvent recovery, and the cost is high; the third is that triethylamine has low catalytic activity and selectivity, and impurities Fourth, the amount of succinic anhydride and reaction solvent in the ingredients is too large, and a large amount of water needs to be added for dilution to precipitate the product. At the same time, the crystallization equipment needs to be too large, and the waste water discharge is also large, and the finished product hydrocortisone semi-amber The yield of acid ester is not high

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis process of hydrocortisone hemisuccinate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Put 130g of dimethylformamide (DMF), 100g of hydrocortisone, 30g of succinic anhydride, and 3g of DMAP into the reaction kettle, and stir at the same time; heat to dissolve, and keep it warm for 3 hours; cool down to 40°C, slowly Add 200g of water, and at the same time lower the temperature to below 10°C, heat and crystallize for 1 hour; centrifuge, filter and wash with water twice; dry for 6 hours at 100°C and a vacuum of 0.095MPa or more to obtain half of hydrocortisone 126.2 g of white crystalline solid of succinate, yield 98.9%.

Embodiment 2

[0030] Put 135g of dimethylacetamide (DMAC), 100g of hydrocortisone, 32g of succinic anhydride, and 6g of pyridine into the reaction kettle, and stir at the same time; heat and dissolve to 45°C, and keep the reaction for 6 hours; Slowly add 200g of water, and at the same time lower the temperature to below 10°C, heat and crystallize for 1.5 hours; centrifugally filter, and wash with water twice, put the washed crystals in a vacuum drying oven, at 105°C, vacuum degree above 0.095MPa , and dried for 6 hours to obtain 125.8 g of hydrocortisone hemisuccinate white crystalline solid with a yield of 98.6%.

Embodiment 3

[0032] Put 130g of dimethylformamide (DMF), 100g of hydrocortisone, 33g of succinic anhydride, and 4g of DMAP into the reaction kettle, and stir at the same time; heat to dissolve, and keep it warm for 4 hours; cool down to 40°C, slowly Add 200g of water, and at the same time lower the temperature to below 10°C, heat and crystallize for 1 hour; centrifuge, filter and wash with water twice; dry for 8 hours at 95°C and a vacuum of 0.095MPa or more to obtain half of hydrocortisone 126.8 g of white crystalline solid of succinate, yield 99.2%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a synthesis process of hydrocortisone hemisuccinate, which comprises the steps of: sequentially adding a solvent, hydrocortisone, succinic anhydride and a catalyst to a reactionkettle according to a feeding ratio, heating the reaction system, starting stirring, carrying out thermal insulation, carrying out a sufficient reaction, cooling, adding purified water, carrying outcrystal precipitation, and carrying out centrifugal filtration, and finally, drying the product in vacuum. Through solvent and catalyst selection and proportion optimization, a single solvent is adopted, the reaction selectivity is high, almost quantitative completion is achieved, the yield reaches 98-99%, and the impurity content is far lower than the limit of BP2013 (British Pharmacopoeia 2013 edition).

Description

technical field [0001] The invention relates to the field of chemical drug synthesis, in particular to a synthesis process of hydrocortisone hemisuccinate. Background technique [0002] Hydrocortisone hemisuccinate is an esterification product of hydrocortisone, which belongs to adrenal glucocorticoid drugs, and has anti-inflammatory, anti-shock and anti-allergic effects. Clinically, it is mainly used for adrenal glucocorticoid insufficiency, allergic diseases such as acute bronchial asthma, bronchitis, and acute ophthalmia, etc. It is also used for high fever caused by some serious infections. Compared with hydrocortisone, its Longer half-life, longer duration of curative effect. In addition, hydrocortisone hemisuccinate can also be used for the preparation of clinical water-soluble corticosteroid hydrocortisone sodium succinate except supplying clinical application, so successfully synthesized hydrocortisone hemisuccinate and improve its output namely appears to be parti...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07J5/00
CPCC07J5/0053
Inventor 吴延柱谢延吴鹏吴楠
Owner 安徽海洋药业有限公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com