Study On New Type Compound Amino Acids(19) And N(2)-L-alany-L-glutamine Injection Tolerance On Health Volunteers

1ObjectiveTo investigate the tolerance and safety of administration rate and dose with new type compound amino acids(19) and N(2)-L-alany-L-glutamine injection in healthy volunteers, and proposed Phase Ⅱ clinical trial of dose regimens.2MethodsThe clinical trial was divided into three parts, including rate tolerant test,dose tolerant test and total parenteral nutrition infusion test.Dropping rate tolerance test:The test was divided into three groups according to droping rates.The droping speed were respectively1mL/min,1.5mL/min,2mL/min,and the dose is250mL.Each group includes eight healthy volunteers (half meales and half females),every volunteer was administrated once.Single peripheral intravenous infusion for different doses of tolerance test:The test was divided into three groups according to doses.The doses were respectively500mL,750mL,1000mL,and the driping speed is2mL/min.Each group includes six healthy volunteers (half meales and half females).Intravenous nutrition infusion and comprehensive test:Six healthy volunteers (half meales and half females) participated in the test.They are all administrated in the same formulation and doses of total nutrient admixture mixed with compound amino acids. The formula of total nutrient admixture were new type compound amino acids(19) and N(2)-L-alany-L-glutamine injection(for wounds),20%fat emulsion, vitamins,glucose,insulin and trace elements.Care:All subjects received ECG monitoring during the entire drug treatment. Observation Indexes:demographic characteristics, vital signs, electrocardiogram, blood routine, urine routine, hepatic and renal function,, coagulation function, adverse events.Evaluation methods:Statistics and analysis of Vital signs,electrocardiogram and laboratory examination before and after administration,and adverse effects were recorded.Describing the occurrence frequency, Severity of adverse events, and analysis the relationship between adverse events and dosage.Analysis the clinical significance of adverse events.3Results(1)The compliance in the test48healthy volunteers who Participated in the test completed in the test,they all have good compliance..(2) Safety tolerance before and after administration,the vital signs (blood pressure, heart rate, body temperature and respiratory rate) ofmost subjects were among the normal ranges, blood pressure, electrocardiogram, blood routine, urine routine, hepatic and renal function, coagulation function, blood glucose and blood lipid indexes before and after administration were normal,No abnormal clinical significance was founded.(3) Adverse eventsIn the test,a small amount of individuals had minor vascular irritation symptoms.No nausea, headache, palpitations and other symptoms were founded, and there was no dose dependent.4ConclusionIt is safe for healthy volunteers to take10%of new type compound amino acids(19) and N(2)-L-alany-L-glutamine injection(for wounds) when infusion rate below2ml/min and the dose was under1000mL or nitrogen≤0.25g/(kg·d). When the dose of total nutrient admixture mixed with compound amino acids under1720mL and average infusion time less than11h, droping rate among2.73+0.32mL.min-1, the human can safely tolerate the total nutrient admixture mixed with compound amino acids.Recommendations for phase Ⅱ clinical trial:It is safe for healthy volunteers to take new compound amino acid (19AA) alanyl-L-glutamine dipeptide injection(trauma used in) when infusion rate below2ml.min-1,dosage at250～1000ml.Total nutrient admixtures is safe at a dose of500～1750ml and andinfusion rate below3ml.min-1The formula of total nutrient admixture were new type compound amino acids(19) and N(2)-L-alany-L-glutamine injection(for wounds),20%fat emulsion, vitamins,glucose,insulin and trace elements and so on.