Studies On Industrial Isolation And Purification Of Spectinomycin

Spectinomycin is a aminocyclol antibiotic which is produced by Streptomyces spectabils.It is mainly used in the clinical treatment of acute gonorrhea,but also used as veterinary drugs and pesticides.With the implementation of generic drug consistency evaluation in recent years,the requirements for raw drugs have been raised to a new level.In this thesis,from the point of process control,the aim of improving the quality of raw materials is achieved by fine control of extraction process,according to the requirement of the highest quality standard(EP).Firstly,the effects of temperature,pH value and time on impurity A,D and E during fermentation broth pretreatment were investigated by means of multiple batches of parallel investigation,and the critical control points of temperature 20℃ and pH 6.61,residence time 24 h were obtained.Through the investigation of the adsorption and analysis process of D152 ion exchange resin,the change curve of related substances was obtained.The removal rates of impurity A,D and E were 21.3%,7.7%and 7.4%,respectively.Combined with the production situation,the effects of crystallization solvent,dosage and temperature on the crystallization related substances of concentrated solution were investigated,and the crystallization conditions of 3.5 times acetone at 30℃ were determined.Through The optimum technological conditions were obtained by investigating the change law of related substances.The impurities A<0.5%,D<0.5%and E<1.0%in the final product were obtained.Secondly,through the investigation of the influencing factors of activated carbon adsorption of endotoxin,1.5%addition was obtained,and more than 97%removal rate could be obtained after 20min,which solved the problem that endotoxin in abnormal batch fermentation was easy to exceed the standard.The 3～10 KD hollow fiber ultrafiltration membrane was investigated.The transmittance of the hollow fiber ultrafiltration membrane was 85～100%.The endotoxin content of the material solution after ultrafiltration was less than 0.09 EU/mL,and the removal rate was close to 100%,which provided a theoretical basis for the selection of production equipment for the removal of lipopolysaccharide by ultra-filtration.Finally,through the investigation of desalting process of nanofiltration washing water,the change curve of washing amount,conductivity and incandescent residue content is obtained.when the amount of washing is more than 4 times and the change rate of conductivity is less than 10%,the content of residue in the liquid tends to be stable.The influence factors of burning residue and heap density in crystallization process were investigated by L16(43)orthogonal experimental design.The technological parameters were determined as follows:crystallization concentration 150000 U/mL,solvent addition rate 1.5 m3/h,crystallization temperature 30℃.The products with low residue content,high heap density and good particle mobility were obtained.In this thesis,the control method of the industrial extraction process of Spectinomycin in the new policy is determined,and the production process with high quality and good stability is obtained.