Abstract:
OBJECTIVE To investigate the causes of inter-batch safety issues of Danshen injections during the production process.
METHODS A two-dimensional evaluation system was adopted: firstly, the macromolecular substance contents of total polysaccharides, proteins, tannins and other macromolecular substances were used as the core detection indexes to determine the effects of the subtle changes of process parameters on the macromolecular substance removal rate of Danshen injections during the refining process; secondly, the safety evaluation model of pyrogenic reaction, allergic reaction, hemolysis and coagulation reaction, and abnormal toxic reaction was used to verify the safety of samples with different levels of macromolecular content, and to explore the correlation between macromolecular residue and product safety risk.
RESULTS Among the refining process parameters of Danshen injections, the changes of the concentration of primary alcoholic immersion paste, concentration of secondary alcoholic immersion paste, pH of alkaline adjusted by alcoholic immersion and pH of acid adjusted by water immersion had a great influence on the macromolecular residues. The samples with low macromolecular residue showed better safety than those with high macromolecular residue in hemolysis and coagulation, abnormal toxicity, allergic reaction, and pyrogenic reaction experiments.
CONCLUSION Differences in macromolecular content between batches of Danshen injections are the key factors leading to the safety problems of Danshen injections.
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