That Such As -3 Cataplasm Toxicological And Their Relative Biological Utilization Research

Objective:To change the Mongolian medicine-Naru-3 water pills into cataplasma, that is to change oral administration preparation form into percutaneous administation preparation form; to determine the reasonable preparation technology and to establish scientific quality control standard; to compare the difference of blood concentration between two kinds of preparation forms: Naru-3 water pills and Naru-3 cataplasma. Methods:1.The preparation technology of Naru-3 cataplasma: radix aconitum kusnezoffii extract was boiled in water, and then separated with macroporous resins; fructus piperis longi was extracted by using ethanol extraction method; fructus chebulae was boiled and filtered to prepare extract; according to cataplasma preparation requirements, parameters of manufacture process were ascertained and preparation technology was established.2.Quality standard of Naru-3 cataplasma: determined the content of meaconitine in Naru-3 cataplasma by high performance liquid chromatography (HPLC); according to cataplasma requirements in appendix of Chinese Pharmacopoeia, testing items were determined.3.Stability experiment of Naru-3 cataplasm: according to scheming quality standard, every test was fufiled by observing remained sample.4.The experiment of pharmacokinetics of Naru-3 cataplasma in rabbit body: rabbits were administrated drugs through oral administration or percutaneous administration; to collect blood of rabbits in different time, and observed the change of plasma concentration between two kinds of preparation forms: Naru-3 water pills and Naru-3 cataplasma and computed the relative bioavailability.5.Toxicological experiment of Naru-3 cataplasma: according to methodology of pharmacological experiment, acute toxicity experiment and long-term toxicity experiment of drugs were fufiled; pertinent items were tested.and pathological condition of tissues was observed. Results:1.The preparation technology of Naru-3 cataplasma: the preparation technology was determined according to each medicine's nature, and then produced Naru-3 cataplasma sample.Naru-3 cataplasma prepared by the method conformed to the regulations.2.The quality standards of Naru-3 cataplasma:defined the HPLC method,inspection item,content limitation of mesaconitine in the preparation,there should be no less than 0.95mg in each cataplasma. Preparation experimental methodologies are complying with inspection requirements.3.Initial stability experiment of Naru-3 cataplasma: observed some samples in the laboratory for three months, examined these samples strictly according to the items in quality standard, including appearance, identification, examination and determination, they all conform to the regulations.4.The experiment of pharmacokinetics of Naru-3 cataplasma in rabbit body: meaconitine can be measured within 1 hour in rabbit plasma by oral administration; plasma concentration of meaconitine was 0.1096μg/ml; plasma concentration of meaconitine was 1.061μg/ml at peak level,and then dropped rapidly, at the 24th hour it reduced to 0.17543μg/ml.Plasma concentration of meaconitine of Naru-3 cataplasma could not be detected when it was given after 1h,at the 3th hour the plasma concentration of meaconitine was 0.1332μg/ml, at the 6th hour it was 0.2098μg/ml, at the 18th hour, it reached the peak level—1.224μg/ml, then the plasma concentration of meaconitine fell slowly, it dropped to 0.1721μg/ml at the 48th hours. And the relative bioavailability reached 183.761%5.The result of toxicology tests showed that there were no obvious pathological changes in the organs of each dose of Naru-3 cataplasma; so it could be regarded as nonpoisonous. Conclusion:Summing up two experimental results, Naru-3 cataplasma can achieve the request of modern preparation of taditonal Chinese medicine by the extraction of radix aconitum kusnezoffii bulleyacontitin, fructus piperis longi, fructus chebulae;Naru-3 cataplasma have effect on expelling wind and removing dampness,promoting blood circulation to stop pain,it can be used to cure wind-damp lumbago,arthralgia,myalgia, sprain and so on.Percutaneous administration can avoid the influence of first pass effect and boost bioavailability significantly.