| Houttuynia Cordata injection is the representative example of the traditional Chinese medicine injections caused clinical adverse reactions(ADRS), the re-research and re-evaluation works of it have very important practical and demonstration significance. A large number of studies found that the material cause of ADRS was the solubilizer used in the Houttuynia Cordata injection. Optimizing the solubilizer is an important point of the re-evaluation works of Houttuynia Cordata injection, that will affect the development direction of the entire TCMI industry.1. Literature ReviewIn this part, we discussed three aspects systematically:①The research situation of intravenous Houttuynia Cordata injection;②The research situation of Tween80 used in injections;③The acute allergic and anaphylactoid reactions of TCMI. These reviews laid the theoretical basis of the overall research paper.2. Experimental StudyThis part included four aspects:①The comparative study on hemolytic effect of different Tween80 and Houttuynia Cordata injection. Through in vitro hemolysis test, combined with macroscopic observation and spectrophotometry, the differences of hemolytic effect on rabbit red blood cells caused by different source and concentration Tween80 and Houttuynia Cordata injection were compared, in order to evaluate the influence of product quality and using concentration of Tween80.②The comparative study on sensitizations of different Tween80 and Houttuynia Cordata injection.Different manufacturers and concentration Tween80 and Houttuynia Cordata injection were selected, through guinea allergic reaction tests, Beagle dogs and food crab monkeys anaphylactoid reaction experiments, the optimum quality and safety concentration range of Tween80 were founded, to ensure the safety of Houttuynia Cordata injection and provide pre-clinical studies basis.③Tween80 cADRiovascular system influence on Beagle dogs. Multiple Tween80 were selected, the blood pressure and heart rate of awake Beagle dogs, the hemodynamics indexes and oxygen intake of anesthesia dog were observed, in order to further validate the safety of Tween80. ④Tween80 pharmic research. United high performance liquid chromatography (HPLC) and evaporation light detector(ELSD), a preliminary inspection of Tween80 from different manufacturers were carried in composition and composition.The conclusions:1.Anaphylactoid reactions characteristics and allergic reaction (anaphylactic shock) performance is very similar, according to the current research and our prophase work, we initially think that anaphylactoid reactions is a kind of comprehensive syndrome which is similar to allergic reaction (anaphylactic shock) performance. The main characteristic of anaphylactoid reactions includes:①High incidence in TCMI, induced in the anaphylactic shock of 2/3;②A variety of material (antigen, half antigen or non-antigen substance), a variety of mechanisms (the complement system activation, directly stimulate target cells to release histamine within a short time, etc.) can induce;③Multiple systems (breathing, cADRiovascular, digestion, skin and mucous membrane)can appear symptoms;④First medication can fast appear symptoms; reaction intensity, symptoms and induce content have obvious concentration-response relations;⑤Contact many times that, reaction induced after symptoms can reduce or disappear, appear tolerance phenomenon.However, at present, the definition, scope, induce substances, pathogenesis, symptoms, diagnosis and differential diagnosis standADR, and the correct method of prevention and treatment of anaphylactoid reactions remain to be further researched. Correct understanding of anaphylactoid reactions has important meaning for TCMI and other drug adverse reactions, especially acute fatal reaction prevention.2. For acute TCMI allergic and anaphylactoid reactions, given its sudden and severity, the key lies in scientific forecast, accurate judgment, and reasonable prevention. TCMI has complicated ingredients, even contains some unknown components.At present, the sensitization research of TCMI still lacks recognized animal models and judgment standADRs. In pre-clinical evaluation on drugs, the false negatie rate of traditional guinea pigs allergy test is high, especially in anaphylactoid reactions.In this research, we suggest, the evaluation of TCMI sensitizations should undertake 2 experiments:①Type I allergic reaction experiment, choose guinea pigs, with symptoms as major decision criteria, IgE rise as auxiliary indicator; ②Anaphylactoid reactions test, choose Beagle dog, with symptoms and histamine rise as the main judgment standADR, the trypsin, complement component testing can be used as auxiliary indexes.3. Tween80 in China at present is the only solubilizer of TCMI, has well increase solution effect to many kinds of dissolved traditional Chinese medicine composition. The use Tween80 in TCMI is an important measures to increase drug solubility and maintain transparent degrees. Because Tween80 itself is a mixture of complicated composition and has certain pharmacological activity and adverse reaction, in clinical application, especially vein, must strictly control the concentration, quality and dosage of Tween80, to ensure safety.Through the series of Tween 80 selection research, we think, improve the Tween80 quality, limite the concentration below 0.3% in TCMI, can ensure the solution effect and avoid the haemolysis, allergic and anaphylactoid reactions occur. Consider the clinical elderly patients and the existence of special circumstances, when use drugs containing Tween80, some risk still exist, need to be vigilant, not careless.4. Tween80 has complicated ingredients, pharmaceutical analysis are promoted, in order to formulate intravenous use Tween80 quality standADRs, and eventually find and remove the Tween80 pre-sensitized ingredients or impurity, which guarantee the safety of intravenous drug useTween80 essentially.Innovation of this research:1. Establish and perfect TCMI sensitization evaluation system. Improve active systemic anaphylaxis in guinea pigs and anaphylactoid reaction in Beagle dogs.For allergic reaction, active systemic anaphylaxis in guinea pigs is preferred; For anaphylactoid reaction, Beagle dog is the preferred, when necessary, monkey is needed.2. Explore the influence of Tween80 on anesthesia dogs hemodynamic indexes and oxygen metabolism. The finding is, Tween80 can cause anesthesia dogs physiological arterial blood pressure, cerebral blood flow and oxygen intake rate decreased obviously, but its influence of cADRiac functions is short. Anesthesia hemodynamic tests can evaluate the influence of Tween80 on cerebrovascular system, kidney and other important viscera, in order to provide reference for the safety of Tween80.3. The preliminary pharmacy analysis on compositions of Tween80.Establish high-performance liquid chromatography and evaporation photodetectors coupled experiment method, preliminary inspectionTween80 for the compositions of the contents and impurities, to evaluate the purity of Tween80. But this method can difficultly segment the chemical composition of each peak, still needs further exploration, so as to provide technical support for improving the quality of Tween80, finding and removing sensitization ingredients.4. Through a series of comparative studies, preferably the quality of Tween80 in TCMI, looking for safe concentration range.
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