Method for extracting a macrolide from biomatter
AssigneeTEVA Gyógyszergyár Zártkörüen MüködöRészvénytársaság
InventorsVilmos Keri, Lajos Deak, Csaba Szabo
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Abstract
Provided is a method for obtaining a macrolide, especially tacrolimus, from biomatter.
Claims30
A method for obtaining a macrolide comprising the step of extracting macrolide-containing biomatter with a hydrophobic extraction solvent to obtain a solution of the macrolide in the hydrophobic extraction solvent, wherein the pH of the macrolide-containing biomatter being extracted is between about 5.5 and about 13.
A method of obtaining tacrolimus from tacrolimus-containing biomatter comprising the steps of:
- a) extracting tacrolimus-containing biomatter that is whole fermentation broth obtained by fermentation of a microorganism selected from the group consisting of Streptomyces tsukubaensis, Streptomyces hygroscopicus, and Streptomyces lividans with a hydrophobic extraction solvent selected form the group consisting of n-butanol, iso-butanol, n-butyl acetate, iso-butyl acetate, t-butyl acetate, ethyl acetate, propyl acetate, ethyl formate, butyl methyl ketone, dichloromethane, chloroform, tetrachloromethane, dichloroethane and toluene to obtain a solution of tacrolimus in hydrophobic extraction solvent at a temperature between about 2° C. and about 70° C. and a pH between about 5.5 and about 13,
- b) separating the tacrolimus-containing solution from the extracted tacrolimus-containing biomatter,
- c) concentrating the tacrolimus-containing solution,
- d) loading the concentrated tacrolimus-containing solution onto a silica gel chromatography column and eluting the column with an eluent to obtain at least one tacrolimus-containing fraction that is a tacrolimus-containing solution,
- d) crystallizing the tacrolimus from at least one tacrolimus-containing fraction whereby a precipitate of crystallized tacrolimus is formed, and
- e) separating crystallized tacrolimus.
The method of clam 20 wherein the crystallization is effected by concentrating the at least one tacrolimus-containing fraction and cooling the concentrated fraction to a temperature of about 25° C. or less.
In a process for obtaining tacrolimus from tacrolimus-containing biomatter, the step of extracting tacrolimus-containing biomatter that is whole fermentation broth with a hydrophobic extraction solvent selected from the group consisting of n-butyl acetate, isobutyl acetate, t-butyl acetate, ethyl acetate, propyl acetate, ethyl formate, butyl methyl ketone, dichloromethane, chloroform, tetrachloromethane, and toluene, wherein the pH of the tacrolimus-containing biomatter is between about 5.5 and about 13.
A method of obtaining tacrolimus from tacrolimus-containing biomatter comprising the steps of:
- a) extracting tacrolimus-containing biomatter that is whole fermentation broth obtained by fermentation of a microorganism selected from the group consisting of Streptomyces tsukubaensis, Streptomyces hygroscopicus, and Streptomyces lividans with iso-butyl acetate to obtain a solution of tacrolimus in iso-butyl acetate at a temperature between about 2° C. and about 70° C.,
- b) separating the tacrolimus-containing solution from the extracted tacrolimus-containing biomatter,
- c) concentrating the tacrolimus-containing solution,
- d) loading the concentrated tacrolimus-containing solution onto a silica gel chromatography column and eluting with an eluent to obtain at least one tacrolimus-containing fraction that is a tacrolimus-containing solution,
- e) concentrating at least one tacrolimus-containing fraction,
- d) crystallizing the tacrolimus from the concentrated fraction, whereby a precipitate of crystallized tacrolimus is formed, and
- d) separating crystallized tacrolimus.
Dependencies are inferred from the claim text.