Process beneficial for quality control of polysaccharide-SPH derivative

Abstract

The invention discloses a process beneficial for quality control of a polysaccharide-SPH derivative. The process comprises the steps of culture, fermentation and purification of an epidemic cerebrospinal meningitis A-group strain and activation and derivation of epidemic cerebrospinal meningitis A-group capsular polysaccharide, wherein culture, fermentation and purification of the epidemic cerebrospinal meningitis A-group strain specifically comprise the steps that the epidemic cerebrospinal meningitis A-group strain is opened and passed to a hemin epidemic cerebrospinal meningitis semi-synthetic medium, and the medium is placed in a carbon dioxide cell culture box to be cultured at the temperature of 36.5 DEG C with 8% CO2; epidemic cerebrospinal meningitis A-group seeds obtained through culture are put in a seed tank in an inoculation mode and then put in a fermentation tank in an inoculation mode after constant-temperature stirring and aerobic culture, the constant temperature is 36.5 DEG C, deep-layer aeration is carried out for stirring culture at 240 rpm, epidemic cerebrospinal meningitis A-group bacteria are cultured till the later period of the logarithmic phase or the early period of the stationary phase, thalli are removed after formaldehyde sterilization, and supernate is collected; polysaccharide is obtained after purification, and the dosage of phenol is 3 / 4 (v / v) that of raw sugar. According to the optimized process, on the one hand, the component content of nucleic acid, protein and other impurities in epidemic cerebrospinal meningitis A-group fermentation liquor is controlled to be low, and on the other hand, the dosage of phenol is lowered.

Description

technical field [0001] The invention belongs to the field of preparation of meningitis group A vaccines, and in particular relates to a process beneficial to the quality control of polysaccharide-SPH derivatives. Background technique [0002] Neisseria meningitidis (N. meningitidis), referred to as meningococcus (meningococcus), is the pathogenic bacteria of epidemic cerebrospinal meningitis (referred to as meningitis). For more than 100 years, ECM has been prevalent or sporadic all over the world, and it is one of the main acute respiratory infectious diseases of human beings. After long-term epidemiological monitoring in many countries, it was found that the disease has the characteristics of periodic epidemics. Italy found three epidemics in its country during 1915-1934. There have also been five national pandemics in my country. In 1938, 1949, 1959, 1967 and 1977, epidemic peaks appeared about every 8-10 years. According to the WHO report, the average incidence rate i...

AI Technical Summary

Problems solved by technology

[0004] To prepare the meningococcal group A conjugate vaccine, the polysaccharide-SPH derivative produced from the meningococcal meningitis group A capsular polysaccharide must first be obtained. However, the current traditional production method needs to first pass the meningococcal meningitis group A capsular polysaccharide through the After culturing and fermentation, the supernatant is obtained, and then the supernatant is purified. However, the ECM A group fermentation broth produced by this traditional method contains more impurities such as nucleic acid and protein. On the one hand, it affects the polysaccharide- The quality of SPH derivatives, on the other hand, increases the difficulty of subsequent purification

And usually need to use more phenol in the above-mentioned purification treatment, and phenol is as a kind of toxic substance, a large amount of use can cause environmental pollution and influence the quality of polysaccharide