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

Preparation method of M2 crystal mycophenolate sodium

A technology of mycophenolate sodium and mycophenolic acid, applied in organic chemical methods, medical preparations containing active ingredients, pharmaceutical formulas, etc., can solve the problem of purity not meeting the requirements of the Pharmacopoeia, high content of mycophenolate sodium impurities, and It is suitable for the production of preparations and other issues, and achieves the effects of easy industrial scale promotion and application, suitable crystal size and low cost

Active Publication Date: 2020-03-27
GUANGDONG BLUE TREASURE PHARMA
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But, prepare mycophenolate sodium with the C1-C4 alcohol solution of mycophenolic acid to obtain M1 crystal form easily, and yield is low; The bulk density of the mycophenolate sodium prepared with the C3-C8 ester solution of mycophenolic acid is lower than 0.3g / ml, not suitable for the production of preparations; the mycophenolate sodium prepared by the C3-C8 ketone solution of mycophenolic acid has high impurity content, and the purity does not meet the requirements of the Pharmacopoeia

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
  • Preparation method of M2 crystal mycophenolate sodium
  • Preparation method of M2 crystal mycophenolate sodium
  • Preparation method of M2 crystal mycophenolate sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1, a kind of preparation method of M2 crystal form mycophenolate sodium

[0029] Include the following steps:

[0030] S1) Dissolve 60g of mycophenolic acid with 1200ml of methyl isobutyl ketone at 50°C, add 1 molar equivalent of dicyclohexylamine, cool down to 10°C, precipitate and filter to obtain solid mycophenolic acid dicyclohexylamine salt , and washed with cold methyl isobutyl ketone to give a wet salt solid;

[0031] S2) Dissolve the wet salt solid in step S1 with 20 times (g:ml) methyl isobutyl ketone at 50°C, add phosphate buffer and wash with stirring for 2h, separate and discard the water layer to obtain mycophenolate The methyl isobutyl ketone solution of acid, the methyl isobutyl ketone solution of mycophenolic acid is divided into mycophenolic acid solution A and mycophenolic acid solution B 30ml;

[0032] S3) Add 35% sodium hydroxide solution dropwise to the mycophenolic acid solution A in step S2 until the pH reaches 10.5 to obtain mycoph...

Embodiment 2

[0035] Embodiment 2, a kind of preparation method of M2 crystal form mycophenolate sodium

[0036] Include the following steps:

[0037] S1) Dissolve 43g of mycophenolic acid with 860ml of methyl isobutyl ketone at 60°C, add 1 molar equivalent of dicyclohexylamine, cool down to 10°C, precipitate and filter to obtain solid mycophenolic acid dicyclohexylamine salt , and washed with cold methyl isobutyl ketone to give a wet salt solid;

[0038] S2) Dissolve the wet salt solid in step S1 with 20 times (g:ml) methyl isobutyl ketone at 60°C, add phosphate buffer and wash with stirring for 2 hours, separate and discard the water layer to obtain mycophenolate The methyl isobutyl ketone solution of acid, the methyl isobutyl ketone solution of mycophenolic acid is divided into mycophenolic acid solution A and mycophenolic acid solution B 20ml;

[0039] S3) Add dropwise 30% sodium hydroxide solution to the mycophenolic acid solution A in step S2 until the pH reaches 9.8 to obtain myc...

Embodiment 3

[0042] Embodiment 3, a kind of preparation method of M2 crystal form mycophenolate sodium

[0043] Include the following steps:

[0044] S1) Dissolve 100g of mycophenolic acid with 1800ml of methyl isobutyl ketone at 50°C, add 1 molar equivalent of dicyclohexylamine, cool down to 10°C, precipitate and filter to obtain solid mycophenolic acid dicyclohexylamine salt , and washed with cold methyl isobutyl ketone to give a wet salt solid;

[0045] S2) Dissolve the wet salt solid in step S1 with 20 times (g:ml) methyl isobutyl ketone at 60°C, add phosphate buffer and wash with stirring for 2 hours, separate and discard the water layer to obtain mycophenolate The methyl isobutyl ketone solution of acid, the methyl isobutyl ketone solution of mycophenolic acid is divided into mycophenolic acid solution A and mycophenolic acid solution B 40ml;

[0046] S3) Add 40% sodium hydroxide solution dropwise to the mycophenolic acid solution A in step S2 until the pH reaches 10.2 to obtain my...

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 belongs to the technical field of drug preparation, in particular to a preparation method of M2 crystal mycophenolate sodium. The preparation method of the M2 crystal mycophenolate sodium comprises the following steps: dissolving mycophenolate acid with methyl isobutyl ketone, adding dicyclohexylamine, cooling, precipitating and filtering to obtain solid mycophenolate acid dicyclohexylamine salt, and washing with cold methyl isobutyl ketone to obtain wet salt solid; dissolving the wet salt solid with methyl isobutyl ketone, adding phosphate buffer solution, washing under stirring, separating the discarded water layer to obtain methyl ethyl butyl ketone solution of mycophenolic acid, and dividing the methyl isobutyl ketone solution of mycophenolic acid into a mycophenolic acidsolution A and a mycophenolic acid solution B; and the mycophenolic acid solution A is dropwise added with sodium hydroxide solution, and the mycophenolic acid solution B is added, cooled, precipitated, filtered, washed and dried to obtain the product. The M2 crystal mycophenolate sodium can be prepared, the yield is high, bulk density is suitable for preparation production, impurity content is low and industrial scale popularization and application can be facilitated.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a preparation method of M2 crystal form mycophenolate sodium. Background technique [0002] Mycophenolate Sodium (trade name of the original drug "Miff") is another drug with mycophenolic acid (also known as mycophenolic acid) as the active drug after mycophenolate mofetil (trade name of the original drug "Xiexi") Component of immunosuppressant, which is metabolized in the body to produce mycophenolic acid (MPA). [0003] Xiaoxi was approved by the US FDA for kidney transplantation in May 1995, and has been approved for heart transplantation and liver transplantation successively. In 1997, it was approved by the Chinese SFDA for listing, and has entered the National Medical Insurance List (Class A) and the Essential Drug List. The listed dosage forms include injections, capsules, tablets, suspensions and dispersible tablets. [0004] Mifu was approved f...

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): C07D307/88A61K31/365A61P37/06
CPCA61P37/06C07B2200/13C07D307/88
Inventor 潘京陈继敏程晓东黄频乐方锐旋
Owner GUANGDONG BLUE TREASURE PHARMA
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