Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of purifying method of 20,23-dipiperidinyl-5-o-mycaminosyl-tylonolide crude drug

A technology of mycaminosyl and dipiperidinyl, which is applied in the field of refining macrolide drug raw materials, can solve the problems of difficulty in obtaining qualified solid products, obstacles, and serious oil formation, and achieve clarification Good degree, lower production cost, low total impurity effect

Active Publication Date: 2017-03-08
武汉回盛生物科技股份有限公司
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Both of the above methods use hydrochloric acid and sodium hydroxide to adjust the pH value, and the product is refined according to the acidity and alkalinity by dissolving between the aqueous phase and the organic phase, without taking out 20,23-dipiperidinyl-5-O- In the process of mycaminosyl-tylonolide hydrochloride, the obtained crude product of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide is difficult to obtain qualified solid The product has a serious oil-forming phenomenon, which seriously hinders the feasibility of the preparation and production of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide

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
  • A kind of purifying method of 20,23-dipiperidinyl-5-o-mycaminosyl-tylonolide crude drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] A method for refining 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide raw material, the steps are as follows:

[0028] Add 10 g of crude 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide into a three-necked flask, add 40 ml of acetone, stir to dissolve, add 5 g of fumaric acid, and stir at room temperature for 1 hour. After the reaction is completed, pour it into 100ml ethyl acetate, a lot of solids appear, filter to get 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide fumarate, 40°C , -0.098Mpa vacuum drying for 5 hours.

[0029] Dissolve the dried 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide fumarate in 50ml of water, stir to dissolve, add 100ml of ethyl acetate, and add 6mol / L The sodium hydroxide solution adjusted pH=8.0-8.5, left to separate layers, separated the water layer, and evaporated the organic layer to dryness to obtain 9.5 g of powdery crude solid, and added 9.5 ml of acetonitrile to recrystallize once to obtain a solid with a purity higher than 99%. .

[...

Embodiment 2

[0033] A method for refining 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide raw material, the steps are as follows:

[0034] Add 10 g of crude 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide into a three-necked flask, add 40 ml of butanone, stir to dissolve, add 5 g of tartaric acid, stir at room temperature for 1 hour, and react After completion, pour into 100ml of ethyl acetate, a large amount of solid appeared, filtered to obtain 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide tartrate, 40°C, -0.098 Mpa was vacuum dried for 5 hours.

[0035] Dissolve the dried 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide tartrate in 50ml of water, stir to dissolve, add 100ml of ethyl acetate, add 6mol / L hydrogen The sodium oxide solution was used to adjust the pH to 8.0-8.5, and the layers were allowed to stand, the water layer was separated, and the organic layer was evaporated to dryness to obtain 9.0 g of a powdery crude solid, which was recrystallized once by adding 9.0 ml of acetonitr...

Embodiment 3

[0038] A method for refining 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide raw material, the steps are as follows:

[0039] Add 10g of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide crude product into a three-necked flask, add 40ml of absolute ethanol, stir to dissolve, add 5g of fumaric acid, and stir at room temperature for 1 hour, after the completion of the reaction, poured into 100ml ethyl acetate, a large amount of solids occurred, filtered to obtain 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide fumarate, 40°C, -0.098Mpa vacuum drying for 5 hours.

[0040] Dissolve the dried 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide fumarate in 50ml of water, stir to dissolve, add 100ml of ethyl acetate, and add 6mol / L The sodium hydroxide solution was used to adjust pH=8.0-8.5, and the layers were left to stand, the water layer was separated, and the organic layer was evaporated to dryness to obtain 9.3 g of powdery crude solid, which was recrystallized once by adding 9.3 ml of ...

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 relates to the technical field of a refining method of macrolides bulk drugs, and in particular discloses a refining method of 20,23-dipiperidinyl-5-O-mycaminose-tylonolide bulk drug. The method comprises the following step: dissolving 20,23-dipiperidinyl-5-O-mycaminose-tylonolide crude product (oil-containing state / oil state) serving as initial raw material in a solvent, adding an organic acid, stirring to form salt, suction-filtering, dissolving the salt by using pure water, adding ethyl acetate, regulating pH to be alkaline, removing a water layer, distilling up an organic layer, recrystallizing the obtained solids by using acetonitrile to obtain 20,23-dipiperidinyl-5-O-mycaminose-tylonolide finished product. The preparation method disclosed by the invention is simple, the refined 20,23-dipiperidinyl-5-O-mycaminose-tylonolide is low in total impurity and high in refining yield, and the injection made from the refined 20,23-dipiperidinyl-5-O-mycaminose-tylonolide is good in clarity.

Description

technical field [0001] The present invention relates to the technical field of refining methods of macrolide drug raw materials, in particular to a refining method of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide raw materials. Background technique [0002] 20,23-Dipiperidinyl-5-O-mycaminosyl-tylosin (Tildipirosin), alias: Tildirosin, is a semi-synthetic macrolide antibiotic, which is the derivative of tylosin derivative. The structural formula is as follows: [0003] [0004] Tildipirosin is the latest macrolide semi-synthetic antibiotic specially developed by Merck for animals. It is a derivative of tylosin. It is more effective than tylosin and tilmicosin, and it has the advantages of special use for animals, less dosage, full treatment with one administration, super long elimination half-life, high bioavailability, and low residue. [0005] Regarding the chemical synthesis method of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide, various synthetic routes have been...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07H17/08C07H1/06A61K9/08A61K31/706
CPCC07H1/06C07H17/08
Inventor 张卫元沈华刘洁薛克友张靖葛健王线郑春红阮夏冰
Owner 武汉回盛生物科技股份有限公司