Study On The Sensitization Evaluation And Comparative Pharmacology Of Houttuynia Cordata Injection In Intravenous

The re-evaluation and re-research of Houttuynia Cordata injection, as the CTMI clinical adverse reactions occurred representatives, are very practical significance. The safety re-evaluation of Houttuynia Cordata injection was be carried out on comprehensive scientific assessments, such as:preparation process, quality standards, pharmacology and toxicology, clinical use and drugs economics. Systematic analysis of the clinical adverse reaction causesd by Houttuynia injection, clear the main allergens, improve production quality standards and preparation process, inhance Houttuynia injection safety, effectiveness and stability, in order to restore production and provide scientific basis for clinical applications.1, Literature ReviewIn the part of literature review, we discussed three aspects:①The reseach of Houttuynia and its preparations;②The analysis and strategy of clinical adverse reaction by Houttuynia injection;③Research for injection accessories of Tween 80 and hydroxypropyl-β-Cyclodextrin. These put forward the theoretical basis for the overall study.2, Study on evaluation of allergenicity of original, new Houttuynia injection and different auxiliariesThis study on allergenicity evaluation the original, new Houttuynia injection and different auxiliaries for used mice, Beagle dogs and rhesus macaque. Anaphylactoid experiment, with single intravenous dose of constant injection, observed changes in behavior of animals after administration and the concentration of histamine. Allergy test was carried out, through intravenous injection of three times to Beagle dogs to immunize, and inject double doses of injections to stimulate in the 9 days after the last sensitized. Observe the allergy situation of Beagle dogs and measure the concentrationns of histamine, IgE in plasma with ELISA after administration in order to determine results. The results show that Beagle dogs to anaphylactoid reactions is the best experimental animal, behavior disorders and histamine concentration as the main index, IgE as the secondary indicator. Rhesus macaque under the same conditions is not sensitive. Atypical behavior and blood indexes in mice are not occurred, its results are not for reference. Tween 80 is the representation of substance-induced anaphylactoid reactions. The results of Hydroxypropyl-β-cyclodextrin in anaphylactoid and allergic reactions are negative. The results in allergenicity evaluation from new Houttuynia cordata injection with hydroxypropyl-β-cyclodextrin as solubilizer are also negative.3, Study on comparative pharmacology of new, original Houttuynia intravenous injectionsIn this study, the model of infected mice with pneumonia influenza virus PR8 and FM1 strains in vivo, CPE in vitro and neuraminidase Fluorescence, viral load testing and death to protect experimental methods were used.The results show that the new Houttuynia injection had obvious effects of treatment and prevention for the pulmonary inflammation resuting form influenza virus infection in mice, improving the pneumonia symptoms, reducing the lung index and viral load, reducing mortality and prolong survival time; but its antiviral activity is not inhibited or killed by the virus directly, the neuraminidase activity is not inhibited. The new preparation could significantly inhibit the swelling degree of mice ear induced by dimethyl benzene and the effusion of Evans blue from capillary permeability induced by acetic acid in mice; they also could decrease the rectal temperature induced by yeast liquid in rats and LPS-induced in rabbit fever. Anti-inflammatory and antipyretic of Houttuynia injection may be inhibitied by the inflammatory cytokines TNF-α, IL-1β, IL-8 and PGE2. Anti virus, anti-inflammatory and antipyretic of new, original Houttuynia injection are quite.4, Establishment of qualitative and quantitative determination of Tween 80 in Houttuynia injectionAmmonium cobalt thiocyanate color method, thin layer chromatography and bismuth potassium iodide was used to the qualitative identification of Tween 80, the results are consistent. Quantitative analysis of Tween 80 can accurately detect the concentration of Tween 80 in TCMI. Qualitative and quantitative methods of Tween 80 can at randomly detect the samples of different manufacturers and batches of TCMI containing Tween 80 under laboratory conditions.The conclusions1, Comparison the similarities and differences between allergy and anaphylactoid reactions induced by TCMITCMI lead to serious adverse in clinical over 70%of anaphylactoid reactions, different to classical IgE-mediated antibody-antigen response. Main features of anaphylactoid reactions are:First injection, serious adverse reactions can be arised, such as anaphylactic shock, and similar syndrome with allergic reactions. It is non-antigen-antibody reaction, no significant changes in IgE and IgG, but histamine significantly increased in vivo. The allergenic substance is antigen or hapten as well as histamine-induced release substances. Obvious dose-effect relationship, it can induce serious adverse in high dose and concentrations. Combined with a variety of injections can increase the incidence and severity. Beagle dogs to anaphylactoid reactions is the best experimental animal, behavior disorders and histamine content as the main index, IgE as the secondary indicator. Therefore, assessment of sensitization in Beagle dogs should be a routine safety testing methods of TCMI in Pharmaceutical factory.2, The major allergenic substances in Houttuynia cordata injection is Tween 80, Houttuynia double-distilled liquid is no obvious side effects.The allergens triggerred adverse reactions of TCMI should account into the drug itself factors, plused accessories in preparation as well as the exogenous and endogenous contaminants in the torage process, which provide ideas in the identification of adverse drug reactions induced by TCMI.3, Tween 80 are widely used at home and abroad. Tween 80 in 134 varieties of TCMI added uncertain.If Tween 80 of all of these species will be replaced must affect the survival of hundreds of manufacturers and hundreds of thousands of industrial workers, social stability and economic impact must be carefully taken into account.4, Hydroxypropyl-β-cyclodextrin is the ideal solubilizer, which has the good solubilization effect, stability, and no significant toxicity, sensitization, hemolytic. New Houttuynia injection with Hydroxypropyl-β-cyclodextrin as solubilizer has good solubility, safety and efficacy, these provide scientific basis for restoring production and clinical applications.5, The factors of Houttuynia injection induced clinical serious adverse are not self-medication, adding Tween 80 in preparation process as well as clinical irrational drug use, but also many incidental one.This study only solve one of the factors of the safety incident of TCMI, but not the all, many studies also need in depth, which will put forward the further research ideas and methods for the comprehensive re-evaluation of CTMI.Innovation of this study1, Comparison with the differences in anaphylactoid and allergic reactions lead to by TCMI:clinical syndrome, pathogenesis, inducing substances, frequency of administration, dosage, test indicators, non-clinical evaluation methods and incompatibility;2, Using different animal experiments in the anaphylactoid research, purpose is the optimization of experimental animals, detection index and allergenicity evaluation method, which can establish the evaluation methods and indicators of anaphylactoid reactions by TCMI;3, Through a series of pharmacy, security research and comparative pharmacology, The new Houttuynia cordata injection with hydroxypropyl-β-cyclodextrin as solubilizer significantly improves the safety, the same efficacy with the original preparation, it has better prospects of development and application in the future.