Safety evaluation method for local use of medicament mucosa

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ABSTRACT:The invention belongs to the field of drug safety evaluation for infectious diseases prevention and mucosa pharmacy, relates to a safety evaluation method for local use of a medicament mucosa, in particular to a safety evaluation method of a medicament based on a mucosa of a cell factor. In the evaluation method, the use safety of the medicament mucosa can be judged by measuring the expression level of the cell factor in an irrigating solution of the mucosa at the medicament-administrating part. Based on the complexity of immunocompetent and cell factor regulated and controlled network, a series of cell factors are used as a measuring and analyzing index, so that the mucosa toxicity of the medicament for the mucosa can be accurately measured, the condition that the medicament induces the mucosa to generate the inflammation can be quickly and sensitively reflected and the dysimmunity activation of local part of the mucosa can be reflected. The evaluation method can be used for preclinical evaluation of a candidate medicament for the mucosa.

Technical Field:The present invention belongs to the field of safety assessment of mucosal disease prevention and treatment, involving a drug safety assessment of mucosal topical, especially based security mucosal drug Thl7 like cytokines mucosal inflammation rating technology.

Background:sexually transmitted diseases has always been a serious threat to human health, it has made unremitting efforts to develop microbicides, including prevention and treatment, including a variety of health drugs to combat these infections by genital tract mucosa viruses or other pathogens. For the problem with these drugs, in addition to considering the effectiveness, its safety must be concerned also.

Any include microbicides, including reproductive tract medication drug candidates before the formal entry into the clinical trial to test the safety of the test must be carried out on animals. Although there are limited animal resources, expensive, heavy workload and other shortcomings, but the animal model can be used to evaluate the complete pharmaceutical dosage form, can be observed from the whole organ level of response to external stimuli, the system can be dynamically observed induced inflammation and the immune response. Therefore animal model to evaluate researchers often viewed as proceeds to step preclinical must do.

The present evaluation include microbicides, including genital or rectal administration in animal models are mainly three types: rabbit vaginal irritation model (Rabbit vaginal irritation, RVI), mice and non-human primate model. Detection index focused on histopathological observations and bacteria detection. Although non-human primate model as one of the safety evaluation, but because of scarce resources and expensive, because it can be coupled with SIV or SHIV infection, and therefore more likely to be non-human primate model for the kill Evaluation of microbial agents of drug candidates and less drug safety evaluation are used.

The rabbit model was used to evaluate the drug's safety vaginal classical model. Rabbit vaginal epithelium by a simple columnar epithelial cells, and therefore has a high sensitivity to external stimuli, but also conducive to the drug safety evaluation. RVI is a standard model with a candidate drug on the cervix and vagina mucosa irritation (once a day for 10 days), the qualitative assessment of anatomy and histopathology both, with a slight (minimal), mild (mild), moderate ( moderate), severe (severe) four levels to represent the severity of the irritation, to assess whether the drug can be used in humans. But in recent years, it was found that the traditional model can not be sensitive RVI reflect an accurate picture of drug safety. For example, the first generation of microbicides N-9 with RVI model when administered to a concentration of 4%, the survey results show safety, but in human clinical trials to prove that it has caused a significant mucosal injury, increased HIV, etc. pathogen infection rates. This is because the traditional model can not RVI sensitively reflect the degree of pathological damage after mucosal administration to mucosal tissue may cause, and these different levels of mucosal injury is critical to enhancing mucosal HIV infection and other pathogenic microorganisms. Hence the need for improvements in the traditional RVI model, not only to the local mucosal drug delivery were observed histopathology, but also found to predict pathological mucosal injury biomarkers improve drug safety evaluation of mucosal sensitivity.