The Development Of Shumianning Compound Antagonist And Its Evaluation Of Clinical Resuscitation And Safety

Shumianning is a kind of compound vein anesthesia preparations developed by our laboratory, which is safe and effective. The clinical application of any kind of anesthetic should have a appropriate antagonist. In this test, a compound antagonist——YF mixture was screened optimally according to the functional characteristic of several drugs in Shumianning. It was indicated that YF compound could make specific antagonism to Shumianning. It was indicated that YF compound could make specific antagonism to Shumianning, quick recovery and high safety when it was used for experiments of anesthetic resuscitation and safety.Experiment I The Experiment of Compound Antagonist Formula for ShumianningObjective:To Find the ideal specific compound antagonists for Shumianning. Methods:based on Shumianning drug ingredients, we selected Yohimbine(Y), Naloxone(N) and Flumazenil(F) for agrypnotic test. Firstly, seven dogs were used for the drug screening tests. At the beginning, four groups of agrypnotic prescriptions were established, Y was used as the first group, YN as the second group, YF as the third group, YNF as the forth group. Then, the best combination drugs were applied to agrypnotic mice anesthetized by Shumianning. Finally, various medicine proportion was optimized through orthogonal test, which made the formula achieve the most ideal state. Results:the compound using of Yohimbine and Flumazenil had the best recovery effect to dogs and the effect of Yohimbine single used was better than Flumazenil. Through orthogonal test, we concluded that the two drugs optimization ratio was 5:2. Preparatory solution contained 0.5 mg of Yohimbine and 0.2 mg of Flumazenil per mL, which was temporary named as Specific Antagonist-YF Mixture.Experiment II Effect of Specific Compound Antagonist on Resuscitation Anesthetized by Shumianning in GreyhoundsObjective:To have an objective evaluate of the recovery effectiveness of YF mixture with monitored the influence of YF on circulation, breathing, temperature in the period of Shumianning anesthesia. Methods:Nine Greyhounds were anesthetized with Shumianning of 0.06 mL·kg-1 intravenously and 10 min after that were injected with compound antagonists intravenously. Dogs were monitored in the phase of whole anesthesia and recovery at 0,1,5,10,12,15,20,25,30,35 and 40 min. Items were measured including resuscitation indexes such as awaken time, stand-up time, after-sleep reaction, wake-up level, pain reflex and muscle tone and changes of physiological parameters, such as heart rate, respiration rate, blood oxygen saturation, breath-out carbon dioxide pressure, systolic blood pressure, diastolic blood pressure and rectal temperature. Results:resuscitation effectiveness of YF mixture was indeed, the time of waking up was 2.13±0.22 min, stand-up time was 5.17±0.63 min, without Complex sleep reaction. It was not only can promote Balanced recovery from sedation, analgesia, relaxation, but also stable recovery of cardiovascular and respiratory function after dogs were anesthetized by Shumianning.Experiment Ⅲ Safety Experiment of Shumianning Specific Antagonis—YF MixtureObjective:To evaluate the safety of the Shumianning specific antagonist—YF mixture. Methods:Mice and rabbits were used as experimental animals and investigated for the safety of YF mixture, including animal spontaneous activities influence test, half of the lethal dose determination test, hemolytic test and local irritation test. Results:There were no significant differences between YF mixture and saline groups in mice spontaneous activity influence test. Half of the lethal dose was 53.292 mg-kg-1; Hemolytic test and local irritation test both conformed to the requirements. Conclusion:the test results of YF mixture showed that it was safe and reliable in clinical utilization.