Preparation Of Compound Gastrodin Dripping Pills And Its Pharmacodynamics Evaluation

ObjectiveTo prepare Compound Gastrodin Dripping Pills (CGDP) composed ofgastrodin and melatonin as active ingredients, and to evaluate the quality,electro-pharmacology and pharmacodynamics of the compound preparation, thisinvestigation was performed.MethodAn orthogonal experiment was designed to investigate the preparingconditions associated with prescription composition such as the ratio betweenactive ingredients and matrix, material temperature, velocity of dripping, and soon. High performance liquid chromatography(HPLC) was employed to determ-ine the contents of gastrodin and melatonin in CGDP. Sodium dithionite wasutilized to set up an anoxia cell model in cultured hippocampal neurons ofneonatal Wistar rats, and MTT agent was used to test the effect of dithionite onneurons survival rates due to anoxia. Patch clamp technique in whole-cellmanner was employed to investigate the effects gastrodin on amplitudes ofvoltage-dependent potassium currents, sodium currents and calcium currents dueto anoxia in presence of dithionite. The characters of currents steady stateactivating and inactivating were also investigated by patch clamp. As forpharmacodynamics, a single-blind experiment with positive control in random-ized manner was designed to compare the effective rate between CGDP and thecontrol. Athens insomnia scale was utilized to evaluate insomnia in66patientsadministrated with CGDP once daily and in51patients administrated withdiazepam tablets orally5-10mg once daily as control.ResultsA qualified dripping pill preparation was obtained with preparingconditions as follows: a ratio between active ingredients and matrix being1:3, material temperature being60℃and velocity of dripping being70/min.Working curves with satisfying precision and recovery rate were establishedaccording to the relationship between peaks area and contents of gastrodin (inrange of1~5μg/mL) or melatonin (in range of14~140μg/mL) using HPLC. Thestability of CGDP was qualified since the contents of gatrodin and melatoninremained invariably in a six-month determining period.Hippocampal neurons were injured by dithionite2.0mmol/L for5min due toanoxia according to the result of MTT method. Amplitudes of transient outwardpotassium currents in hippocampal neurons were depressed due to anoxiainduced by dithionite. Fitted with Boltzmann Equation, the course of steadystate activating of outward rectifier potassium currents shifted to right along themembrane potential axis in the presence of anoxia, and the course of steady stateinactivating of sodium currents altered to left, which indicated that neuronsbecame excitable because of anoxia, but with a less depolarizing ability.Gastrodin antagonized the effect of anoxia on outward rectifier potassium inhippocampal neurons.In elderly patients with insomnia, insomnia was alleviated in experimentgroup66patients administrated with CGDP15pills once daily. Comparing withcontrol group51patients administrated with diazepam tablets5-10mg oncedaily, the effective rate (33%) in experiment group was less than that (88.2%) incontrol group（P<0.05）.ConclusionThe preparation of CGDP was practicable because of its stability andrepeatability. Gastrodin depressed the increased excitability of neurons inpresence of dithionite. CGDP was effective in dealing with insomnia in elderlypatients, but not equal to diazepam.