Studies On Pharmacodynamics And Pharmacokinetics Of The Lentinan Liposome

Lentinan,a kind ofβ-(1→3) polyglucosan,is isolated from fruiting body of lentinusedodes.As a immunoenhancer, The Lentinan is offen used in many clinical applications with the antineoplastic agents. Through enhancing phagocytic capacity, T lymphocytes and NK cells, the Lentinan leads to a wide range of pharmacological effects such as anti-tumor, anti-virus, enhance immune function and stimulate the interferon formation and so on. However, because the half-life of the Lentinan in the body is short, its clinical application is limited. Therefore, Daan Pharmaceutical in Wuhan , liposomes modified formulations is conducted with a view to further enhance its effects, prolong the extension time of Lentinan in vivo, improve efficacy of Lentinan, enhance its clinical application. This experiment is based on transforming formulations, studying the pharmacodynamics and pharmacokinetics of lentinan liposome to find out its Pharmacodynamic effects,Metabolism,Mechanism and provide data of the route of administration and a valuable reference dose.1 Studies on pharmacodynamics of the lentinan liposome1.1 Studies on pharmacodynamics of the lentinan liposome in normal miceThe experimental mouse was injected with high, middle, and low dosages of Lentinan Liposome (0.5,1,3 mg·kg^-1·d^-1) in the abdomen(i.p.), Lentinan Injection (1mg·kg^-1·d^-1) and the comparison group was given the same volume of glucose i.p.once a day. After treatment for 10 consecutive days,carbon granular clearance, the weight of immune organ , the ability of the spleen lymphocytes proliferation and the hemolysin production test were used to evaluate the influence of the Lentinan liposome on immunity in normal mice.The results are that the Lentinan liposome can promote the carbon granular clearante; accelerate the proliferation of T lymphocyte in blood and spleen; enhance the hemolysin production ,and the effect is correlated with dosage.The Lentinan injection still can improve the immune regulatory effect ,but it is weeker than liposome when it dealed with statistics.1.2 Studies on pharmacodynamics of the Lentinan liposome in tumor-bearing miceH22-bearing mouce were used as animal mode.The efects on tumor weight and immune function were investigated, the Antitumor rate is used to evaluate the influence of Lentinan liposomes conjunction with the cyclophosphamide in the tumor-bearing mouce, Determinations such as phagocytic phagocytosis in liver, transformation rate of T lymphocyte in spleen and anti-functional of NK cells in spleen were used to illuminate the pharmacodynamic action and mechanism of Lentinan liposomes. The results are that Lentinan liposomes conjunction with the cyclophosphamide can promote the Antitumor rate; Lentinan liposomes can not affect Antitumor;Lentinan liposomes conjunction with the cyclophosphamide or separate both can promote phagocytic phagocytosis in liver,enhance the proliferation of T lymphocyte in spleen,and accelerate the NK cells of anti-functional in spleen.1.3 Studies on pharmacokinetics of the Lentinan liposomeTo study pharmacokinetics of the Lentinan liposome in Beagle dogs serum. The LAL method is used in quantitative detection of Lentinan. This method is sensitive and accurate, quicker and good repeatability in detection of Lentinan in serum of Beagle dogs were bolused Lentinan liposome and Lentinan injection in vein,DAS software used to calculate pharmacokinetic parameters.The Tmax;Cmax,AUC0-∞and t1/2 of Lentinan liposome after 0.15 mg·kg^-1 administration in dogs were 0.115±0.075(h) , 117.04±10.18 (ng·ml^-1),1344.67±214.40 (ng·h·ml^-1) and 9.54±1.78(h). The Tmax;Cmax,AUC and t1/2 of Lentinan injection after 0.5mg·kg^-1 administration in dogswere0.104±0.101(h), 87.71±14.57(ng·ml^-1),123.64±53.26(ng·h·ml^-1),0.92±0.33(h).