The Preparation Of Compound Ketamine Oral Solution And The Investigation Of It's Animal And Clinical Application

Children are immature in nervous system and psychology, it is hard to quiet them through explanation and persuasion before operation . when they are taken off their parents into operation room ,they become scared and struggle to escape. This situation influences on the safety of anesthetic induction and costs medical professional energy and makes environment noisy. The dread do harm to children on psychology and nervous system especially to the children who underwent operation more than one time and their parents.Now many drugs such as Ketamine, Dormicum, ( KD) in enough dosage can make preoperation sedation . KD combinative application is a relatively ideal choice. But the route of medication is a difficult problem in concern with characteristics of children. Drug injection itself can make children cry and struggle. Medication through rectum or nose is uneasy to be accepted by children, and the dosage is inaccurate. Oral medication is a simple method and easy to accept, but drug savor is bitter . so we have to mix the drug with many sweet solution which may cause regurgitation and aspiration, children dislike taking it and ease to result in loss of drug solution and inaccurate dose of drug affect on the effect of drug.This study prepared a kind of Compound Ketamine (including Ketamine Dormicum and Atropine KDA) oral solution which have good taste and small volume and easy to be accepted. We studied the clinical feasibility from three parts: a. the best formula; b. mechanism; c. evaluation of clinical effect. From this study we could get theory support and practical experience for clinicalapplication and spread. This study consisted of three parts. The first part; the preparation of pediatric oral solution of premedication . we studied the stability of mixture of KET, DMC, AT and supplemental material with the DSC( Differential Scanning Carlorimetry ) method; selected better taste with quadrature test; determined the stability through study the changes of clarification degree, pH value and concentrations. The second part: to study the KDA oral solutions effect on the function and conformation of immature mice; to discuss the mechanism of KDAs anxiolytic effects through study of effects on behavior, gastric stimulation, GABAAR,NMDAR, and its toxicity. The third part: to investigate clinical application of KDA oral solution and determine its pharmacokinetics; to test its value of clinical application and feasibility .Experimental Materials1. Raw material and different oral solution prescription-. KET ^ DMC ^ AT and supplement material. Four different oral solution prescription; (I) KDA oral solution : Each ml contains 50mg of KET, 5mg of DMC, 0. 3mg of AT with added condiment is one dose. (2) KD oral solution; Each ml contains 50mg of KET , 5mg of DMC with added condiment. (3) KET oral solution; Each ml contains 50mg of KET with added condiment. (4) DMC oral solution; Each ml contains 5mg of DMC with added condiment which forms different oral administration products with different taste. Irrigate rat stomatch with 2ul . g-1.2. Main reagent;1) Immunohisto-chemistry; One antibody; NMDAR1, AB1516 50ug (CHEMICON American Company ) Immunohisto-chemistry dyeing reagent one set (Beijing Zhong Shan biological technique company)2) Hybrid in situ: Hybrid in situ reagent kit GABAAR MK1187 ( Wuhan Boshi De Shengwu Gongcheng company) ; GABAA R nucleic acid probe sequence :5'-GTCTG AAACG GGTCC GAAAC TGGTG ACGAA-3'3. Experiment animal ; Select Sprague-Dawley (SD) rat,age between 5 ~6 weeks, weight between 150 ~200g.4. Main equipments; DSC-60 Heat Analyizer(Japan); High-Performace Liquid Chromatography ( HPLC ) (Japan); pHS-3C acidic agent ( China); U-MCB Olympus Photographic system ( Japan) ; BX60 Olympus microscopic camera ( Japan ) ; METAMORPH/COOL SNAP + X/AX70 microscope ( fluorescence ) photograph analyzing system ( VIC/ROPER/OLYMPUS ) US/JP; CM 1800 LEICA frozen slicer (Germany) ; LKB-V type ultrathin slicer(Sweden ); H-600 Penetration ele...