Method for purifying lincomycin

Abstract

The invention belongs to the technical field of medicine products and relates to a method for purifying lincomycin. The method mainly comprises the following steps: after acid regulation, fermentation broth undergoes filter pressing and then undergoes alkali regulation and ultrafiltration membrane filtration; after undergoing nanofiltration concentration, filtrate is extracted through a binary extraction agent composed of benzyl alcohol and dichloromethane, purified water is added into an organic phase obtained through separation to perform back extraction, finally back extraction liquid undergoes vacuum concentration and then acetone is added to perform crystallization, and finished lincomycin is obtained after drying. According to the method, an extraction effect is good, particularly an effect of removing a byproduct component B is excellent, the process cost is low, and the method has very high feasibility for large-scale industrial production of lincomycin.

Description

technical field

[0001] The invention belongs to the technical field of pharmaceutical products, and relates to a method for purifying lincomycin, in particular to a method for extracting lincomycin with a binary mixed extractant. Background technique

[0002] Lincomycin is an alkaline broad-spectrum antibiotic that is effective against most Gram-positive bacteria and is clinically used for the treatment of infections caused by Staphylococcus aureus, Streptococcus viridans, and Streptococcus pneumoniae. Clindamycin, developed with lincomycin as the raw material drug, is commonly used in the treatment of various diseases such as sepsis, respiratory system infection, and skin and soft tissue infection.

[0003] Lincomycin is an antibiotic isolated mainly through microbial fermentation and culture. There are multiple chiral centers in its molecular structure and multiple isomers. Lincomycin mainly produces lincomycin A during the fermentation process. In addition to the compone...

Examples

Embodiment 1

[0035] Take 300Kg of lincomycin fermentation broth, add oxalic acid to adjust the pH to 3, and filter through plate and frame to obtain the filtrate;

[0036] Use NaOH to adjust the pH of the filtrate to 11, pass the alkalized solution through a ceramic ultrafiltration membrane for ultrafiltration, the pore size of the ultrafiltration membrane is 0.1 μm, the reflux valve controls the membrane inlet pressure ≤ 1.0Mpa, and the temperature is controlled at 10 ° C ~ 35 ° C, Obtain ceramic membrane permeate;

[0037] The permeate is concentrated 10 times through the nanofiltration membrane, the pore size of the nanofiltration membrane is 0.001 μm, and the concentrated nanofiltration solution is obtained;

[0038] NaOH adjusts the pH of the nanofiltration concentrated solution to 12, adds 1 / 10 times of concentrated solution volume benzyl alcohol and dichloromethane binary extractant to the concentrated solution, the ratio of benzyl alcohol is 60%, stirs for 30min, the material in th...

Embodiment 2

[0045] Take 350Kg of lincomycin fermentation broth, add hydrochloric acid to adjust the pH to 5, and filter through plate and frame to obtain the filtrate;

[0046] Use NaOH to adjust the pH of the filtrate to 9, pass the alkaline solution through the ceramic ultrafiltration membrane for ultrafiltration, the pore size of the ultrafiltration membrane is 0.1 μm, the backflow valve controls the membrane inlet pressure ≤ 1.0Mpa, and the temperature is controlled at 10 ° C ~ 35 ° C, Obtain ceramic membrane permeate;

[0047] The permeate is concentrated 10 times through the nanofiltration membrane, the pore size of the nanofiltration membrane is 0.001 μm, and the concentrated nanofiltration solution is obtained;

[0048] Use NaOH to adjust the pH of the nanofiltration concentrate to 10, and add 1 / 5 times the volume of the concentrate to the lincomycin concentrate at one time. Stir for 30 minutes, control the temperature of the feed liquid at 10°C during the extraction process, separ...

Embodiment 3

[0053] Take 310Kg of lincomycin fermentation broth, add oxalic acid to adjust the pH to 3, and filter through plate and frame to obtain the filtrate;

[0054] Use NaOH to adjust the pH of the filtrate to 11, pass the alkalized solution through a ceramic ultrafiltration membrane for ultrafiltration, the pore size of the ultrafiltration membrane is 0.1 μm, the reflux valve controls the membrane inlet pressure ≤ 1.0Mpa, and the temperature is controlled at 10 ° C ~ 35 ° C, Obtain ceramic membrane permeate;

[0055] The permeate is concentrated 5 times through the nanofiltration membrane, the pore size of the nanofiltration membrane is 0.001 μm, and the concentrated nanofiltration solution is obtained;

[0056] Adjust the pH of the nanofiltration concentrated solution to 12 with NaOH, add 1 / 4 times the volume of the concentrated solution to the concentrated solution, benzyl alcohol and dichloromethane binary extractant, the ratio of benzyl alcohol is 80%, stir for 30min, the mater...

technical field

[0001] The invention belongs to the technical field of pharmaceutical products, and relates to a method for purifying lincomycin, in particular to a method for extracting lincomycin with a binary mixed extractant. Background technique

[0002] Lincomycin is an alkaline broad-spectrum antibiotic that is effective against most Gram-positive bacteria and is clinically used for the treatment of infections caused by Staphylococcus aureus, Streptococcus viridans, and Streptococcus pneumoniae. Clindamycin, developed with lincomycin as the raw material drug, is commonly used in the treatment of various diseases such as sepsis, respiratory system infection, and skin and soft tissue infection.

[0003] Lincomycin is an antibiotic isolated mainly through microbial fermentation and culture. There are multiple chiral centers in its molecular structure and multiple isomers. Lincomycin mainly produces lincomycin A during the fermentation process. In addition to the compone...

Examples

Embodiment 1

[0035] Take 300Kg of lincomycin fermentation broth, add oxalic acid to adjust the pH to 3, and filter through plate and frame to obtain the filtrate;

[0036] Use NaOH to adjust the pH of the filtrate to 11, pass the alkalized solution through a ceramic ultrafiltration membrane for ultrafiltration, the pore size of the ultrafiltration membrane is 0.1 μm, the reflux valve controls the membrane inlet pressure ≤ 1.0Mpa, and the temperature is controlled at 10 ° C ~ 35 ° C, Obtain ceramic membrane permeate;

[0037] The permeate is concentrated 10 times through the nanofiltration membrane, the pore size of the nanofiltration membrane is 0.001 μm, and the concentrated nanofiltration solution is obtained;

[0038] NaOH adjusts the pH of the nanofiltration concentrated solution to 12, adds 1 / 10 times of concentrated solution volume benzyl alcohol and dichloromethane binary extractant to the concentrated solution, the ratio of benzyl alcohol is 60%, stirs for 30min, the material in th...

Embodiment 2

[0045] Take 350Kg of lincomycin fermentation broth, add hydrochloric acid to adjust the pH to 5, and filter through plate and frame to obtain the filtrate;

[0046] Use NaOH to adjust the pH of the filtrate to 9, pass the alkaline solution through the ceramic ultrafiltration membrane for ultrafiltration, the pore size of the ultrafiltration membrane is 0.1 μm, the backflow valve controls the membrane inlet pressure ≤ 1.0Mpa, and the temperature is controlled at 10 ° C ~ 35 ° C, Obtain ceramic membrane permeate;

[0047] The permeate is concentrated 10 times through the nanofiltration membrane, the pore size of the nanofiltration membrane is 0.001 μm, and the concentrated nanofiltration solution is obtained;

[0048] Use NaOH to adjust the pH of the nanofiltration concentrate to 10, and add 1 / 5 times the volume of the concentrate to the lincomycin concentrate at one time. Stir for 30 minutes, control the temperature of the feed liquid at 10°C during the extraction process, separ...

Embodiment 3

[0053] Take 310Kg of lincomycin fermentation broth, add oxalic acid to adjust the pH to 3, and filter through plate and frame to obtain the filtrate;

[0054] Use NaOH to adjust the pH of the filtrate to 11, pass the alkalized solution through a ceramic ultrafiltration membrane for ultrafiltration, the pore size of the ultrafiltration membrane is 0.1 μm, the reflux valve controls the membrane inlet pressure ≤ 1.0Mpa, and the temperature is controlled at 10 ° C ~ 35 ° C, Obtain ceramic membrane permeate;

[0055] The permeate is concentrated 5 times through the nanofiltration membrane, the pore size of the nanofiltration membrane is 0.001 μm, and the concentrated nanofiltration solution is obtained;

[0056] Adjust the pH of the nanofiltration concentrated solution to 12 with NaOH, add 1 / 4 times the volume of the concentrated solution to the concentrated solution, benzyl alcohol and dichloromethane binary extractant, the ratio of benzyl alcohol is 80%, stir for 30min, the mater...

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