| ObjectiveAfter early screening,the combination of YN and TV1 was used to prepare YNT plastics for transdermal absorption preparation.The antithrombotic and anti-inflammatory effects of YNT plastics were preliminarily discussed,and the effect of YNT coating agent was investigated.The transdermal absorption characteristics of YN plastics and TV1 plastics were studied,and the theoretical basis and method reference were provided for the transdermal absorption experiment of YNT plastics and the study of percutaneous drug delivery.MethodThe effects of YNT plastics on experimental of cerebral thrombosis in rats were divided into sham operation group,model group,YN plastics(10 mg/kg),TV1 plastics group(3.33 mg/kg),YNT high(TV1:YN 6.67:10 mg/kg),YNT medium(TV1:YN 3.33:10 mg/kg)and YNT low(TV1:YN 1.67:10 mg/kg)dose groups.The behavioral score,blood rheology,blood coagulation and fibrinolysis system function,and the content of inflammatory cytokines IL-6,IL-10,IL-1? andTNF-? in brain tissue were used as test indexes to investigate the effect of YNT plastics on cerebral thrombosis in rats.The effect of YNT plastics on thrombosis in mice was induced by the injection of collagen adrenaline compound inducer in the tail vein to induce the mouse hemiplegia model,which was divided into normal group,model group,YN plastics group(20 mg/kg),TV1 plastics group(18.88 mg/kg),YNT high(TV1:YN 37.75:20mg/kg),medium(TV1:YN 18.88:20 mg/kg)and YNT low(TV1:YN 9.44:20mg/kg)dose groups.taking the thrombosis in mice and the pathological changes of lung tissue of hemiplegic mice as the test index,to investigate the effect of YNT plastics on thrombosis in mice.\The effect of YNT plastics on the anti-inflammatory effect of mice in vivo was divided into normal group,model group,aspirin group(200mg/kg),YN plastics group(20 mg/kg),TV1 plastics group(18.88 mg/kg),YNT high(TV1:YN 37.75:20mg/kg),medium(TV1:YN 18.88:20 mg/kg)and YNT low(TV1:YN 9.44:20mg/kg)dose groups,induced mouse ear swelling,carrageenan induced foot swelling and mouse peritoneal capillary permeability hyperactivity model.TV1:YN 18.88:20mg/kg and YNT low(TV1:YN 9.44:20 mg/kg)dose group.The effect of YNT plastics on the anti-inflammatory effect of mice was observed by using the difference between the mouse ear foot swelling and the abdominal capillary permeability.Experimental study on YNT plastics transdermal absorption characteristics: To investigate the transdermal absorption characteristics of YN plastics in vitro,using improved TPY-2 type transdermal diffusion test instrument and HPLC method to determinate the YN content;Using ADP to induce platelet aggregation in vivo to form a thrombus model,and turbidimetry to determinate the platelet aggregation rate,to investigate the effect of YN on platelet aggregation,detecting the blood concentration of YN in vivo by HPLC;Using improved TPY-2 type transdermal diffusion test instrument to establish the experimental method of transdermal absorption of TV1 plastics in vitro.The experimental study on the transdermal absorption of YN plastics and TV1 plastics provided a reference and experimental basis for the transdermal absorption experiment of the subsequent YNT plastics.Result1 Preliminary antithrombotic and anti-inflammatory activities study of YNT plastics1.1 Effect of YNT plastics on cerebral thrombosis in ratsThe experimental results showed that: Sham operation group had noabnormality in neurobehavioral;Model group had obvious loss of nerve function;Compared with the model group,YNT(TV1:YN)plastics high,medium and low(6.67:10 mg/kg.BW,3.33:10 mg/kg.BW,1.67:10 mg/kg.BW)dose group,the neurological function had recovery trend,the 24 h nerve function scores in the TV1 group and the high dose group decreased significantly(P<0.05);High,medium and low(6.67:10 mg/kg.BW,3.33:10 mg/kg.BW,1.67:10 mg/kg.BW)dose group had lower the whole blood viscosity shear rate in 10/s,60/s,150/s,200/s and the Casson viscosity trend;High dose group could significantly reduce whole blood viscosity1/s,the erythrocyte aggregation index(P<0.05);hinted that YNT plastics could improve nerve function deficiency,blood viscosity,blood flow,so then inhibiting cerebral thrombus formation and development.Compared with the model group,the content of IL-6 in YNT high(6.67:10mg/kg.BW)dose group increased significantly(P<0.05),YNT plastics high and low(6.67:10 mg/kg.BW,1.67:10 mg/kg.BW)dose group IL-10 content of brain tissue had increased trend;low(1.67:10 mg/kg.BW)dose group TNF-? of brain tissue was significantly lower(P<0.05),high,medium dose group TNF-? content of brain tissue had decreased trend,hinted that the protective mechanism of YNT plastics may be related to the expression of inflammatory cytokines in the brain.Compared with the TV1 plastics group,YNT plastics had no significant difference in inhibiting the formation and development of experimental cerebral thrombosis in rats,the addition of YN did not increase the efficacy of YNT plastics.1.2 Effect of YNT plastics on internal thrombosis in miceThe experimental results showed that the YNT(TV1:YN)plastics in high(37.75:20 mg/kg.BW)dose group could significantly prolong the formation time of mice hemiplegia(P<0.05),the pathological results showed that lung tissue of mice in high dose group had mild congestion,no obvious hemorrhage,it indicated that YNT plastics maybe has certain inhibit the formation and development of internal thrombosis in mice;Compared with the TV1 plastics group,YNT plastics had no significant difference in inhibiting thrombosis in mice,the addition of YN did not increase the efficacy of YNT plastics.1.3 Effect of YNT plastics on the anti-inflammatory effect of miceThe experimental results showed that: YNT(TV1:YN)plastics high,medium and low(37.75: 20 mg/kg.BW,18.88:20 mg/kg.BW,9.44:20 mg/kg.BW)dose groups had the trend of inhibiting the hyperpermeability of peritoneal hypercapillaries,and the low(9.44:20 mg/kg.BW)dose group had the trend of inhibiting the ear swelling,it indicated that YNT plastics maybe had anti acute inflammation effect,and its anti-inflammatory mechanism needs further study;Compared with TV1 plastics,YNT plastics had no significant difference in anti-inflammatory effect,the addition of YN did not increase the efficacy of YNT plastics..2 Preliminary study on transdermal absorption characteristics of YNT plastics2.1 Experiment of transdermal absorption of YN plasticsThe experimental results showed that the established method of YN content determination had good results.The method was scientific and reliable,and was suitable for the transdermal absorption experiment of YN plastics.2.2 The establishment of anti platelet aggregation of YN plastics and the determination of blood drug concentration in vivoThe experimental results showed that YN plastics had certain inhibitory effect on platelet aggregation induced by ADP in rats,the maximal inhibition rate and the highest blood concentration were found at 30 min.2.3 Exploration of the method of transdermal absorption of TV1 plastics in vitroIt preliminarily discovered that in the transdermal absorption experiment of TV1,the B peak of TV1 began to penetrate the skin into the receiving liquid at 2 h,after transdermal absorption of 72 h,the B peak of TV1 in the receiving liquid could still be detected,and the rest of the peak was not detected for the time being in the receiving liquid.ConclusionIn summary,YNT plastics could improve the loss of nerve function,improve blood viscosity in rats,so then had a certain effect on the inhibition of experimentalrats with cerebral thrombosis,and to a certain extent,the formation and development of thrombus in mice may be effective,may also had anti-inflammation effect,the addition of YN did not increase the efficacy of YNT plastics in antithrombotic and anti-inflammatory effects,it provided experimental basis and new ideas for the further research into YNT combined use of drugs;Exploration of the method of TV1 plastics transdermal absorption and the determination method of YN content for subsequent YNT transdermal experiments in vitro and in vivo,provided useful reference for research and development. |
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