| [Objective]Dragon's blood is a kind of renowned traditional Chinese medicine which has many pharmacological activities,but its solubility is low.This project was aimed to improve the solubility components in Longxuejie(Chinese dragon's blood,CDB),increase the use of multicomponent biological CDB in order to improve the solubility.The final inspection is to investigate the effect of CDB on the blood pressure and blood biochemical parameters in the cynomolgus monkeys,and compare the data before and after the solubility improved.This project was a modified release of insoluble components of traditional Chinese medicine(TCM),which provided the basis for the two development of CDB,including the new use,and had important research value and significance.[method]1.first,cyclodextrin(P-CD),hydroxypropyl beta cyclodextrin(HP-beta-CD)and polyvinylpyrrolidone K30(PVPk30)was used as carrier materials and preparation to make Longxuejie beta-CD clathrate(CDB-beta CD),Longxuejie(HP-beta-CD clathrate CDB-HP)and blood PVPk30 solid dispersion(CDB-PVP)by solvent method.Then,the content of B CDB in blood index components was determined by HPLC method,and to determined CDB inclusion complexes,CDB-PVP solubility and in vitro dissolution,render the dissolution curve;Fu Liye infrared spectroscopy,differential scanning calorimetry and X-ray diffraction were used tocharacterize the structures.2.by Na NO2-Al(NO3)3-Na OH solubility colorimetric determination of total flavonoids in Resina Draconis and total flavonoids in different solvent conditions;in simulated gastric conditions(p H=1.2)determination of solubility of CDB-beta CD,CDB-HP and CDB-PVP of the proportion of total flavonoids.3.screening of hypertension in cynomolgus monkeys 20 rats were randomly divided into CDB group(high dose was 4 times that of the low dose group of0.72g/kg),CDB(low dose group according to the body weight is converted into the monkey dose,0.18g/kg),CDB-PVP group(including CDB and CDB low dose group,1.39g/kg),positive control group,according to the body weight converted into macaques dose,7.52mg/kg),model group,and normal blood pressure in cynomolgus monkeys into blank control group,4 rats in each group,except the blank group and model group,intragastric administration with corresponding drugs,each d gavage 1 times a week,6D the rest,1D,for 1 courses,4 courses.Blood pressure is measured the next day.On the last day before and after intragastric administration,fasting blood was taken to examine the routine blood routine,liver and kidney function,and blood coagulation four items.[results]1.Preparation of CDB-,CDB-HP and CD beta CDB-PVP,solubility and in vitro dissolution of Loureirin B was significantly increased compared with raw materials.(1)in the experiment of measuring the solubility and CDB of Loureirin B in solubility as evaluation index,CDB raw materials and physical mixture were not detected in Loureirin B,the solubility is 0;CDB-beta CD(1:6,1:12,1:18,w/w)the equilibrium solubility were 11.16 g/ml,16.28 g/ml,22.07 g/ml(CDB-HP;1:6,1:12,1:18,w/w)the equilibrium solubility were34.53 g/ml,57.74 g/ml,58.03 g/ml;CDB-PVP(1:2,1:4,1:6.5,1:9,w/w)the equilibrium solubility were 0.51 g/ml,38.34 g/ml,95.34 g/ml,101.29 g/ml.(2)in the experiment of measuring the dissolution rate,CDB-beta CD(1:6,1:12,1:18,w/w)were not detected in Loureirin B,the dissolution rate is 0;CDB-HP(1:6,1:12,1:18,w/w)in 5min,10 min in the cumulative dissolution percentage were 2.2%,7.5%,11.7% and 6.9% in 25.2%,15.3%,and 120 min cumulative dissolution percentage were 73.1%,75.4%,88.9%,compared with the raw materials CDB were significant difference(P<0.01),and the dissolution and the dissolution rate increased with the amount of-CD beta HP-(1:6,1:12,1:18 and t test group,P <0.05 CDB-PVP);Loureirin B in the dissolution and dissolution rate,also has the very big promotion,CDB-PVP(1:9)in the 5min and 10 min cumulative dissolution were 4.3% and 14.6%,compared with the raw materials of CDB have significant difference(P<0.01),1:6.5 and 1:9 solid dispersion in 120 min Loureirin B tired Product dissolution percentage is as high as 73%,and the dissolution percentage is proportional to the amount of PVP more(1:6,1:12,1:18 and t test group,P <0.05);CDB-HP and CDB-PVP were compared in vitro,and CDB-HP was more advantageous in improving dissolution(P<0.05).2.The crystal structure of CDB changed significantly under the action of HPbeta-CD and PVP.(1)the results of IR showed that the peak of CDB-HP and CDB-PVP have shifted,the intensity is dramatically reduced,and the absorption peak has a Obvious change in the corresponding scanning range.(2)the results of DSC showed that the thermal stability of CDB-HP and CDB-PVP is good,and the exothermic peak decreases with the increase of the ratio of carrier materials.(3)the results of X ray diffraction showed that the characteristic peaks of CDB-HP and CDB-PVP were weakened or even disappeared in different degrees,which proved that the combination ofdragon's blood and carrier meterial forms a complex.3.The solubility of total flavonoids in dragon's blood is different under different solvent conditions(p H1.2,2,4,6.8,7.4 and water).(1)the content of total flavonoids in dragon's blood was 341.271mg/g.(2)the solubility of total flavonoids in p H1.2,2,4,6.8,7.4 and water was 1.481,1.181,2.712,1.444,1.152 and 2.106mg/m L,respectively.(3)CDB-beta CD(1:6,1:12,1:18)solubility of total flavonoids were 1.414,0.997,1.187mg/m L;CDB-HP(1:6,1:12,1:18)solubility of total flavonoids were 0.844,3.369,2.194mg/m L;CDB-PVP(1:2,1:4,1:6.5,1:9)the solubility of total flavonoids in different0.540,0.722,5.622,4.023mg/m L.4.The effects of CDB and CDB-PVP on the systolic blood pressure,diastolic blood pressure,platelet and activated prothrombin time(APTT)were observed in cynomolgus monkeys.(1)systolic blood pressure of high dose CDB group in cynomolgus monkeys significantly reduced weekly after administration(P<0.01),in CDB-PVP group had the effect of lowering the systolic blood pressure on cynomolgus monkey in the third week(P<0.05),CDB low dose group showed no decrease systolic pressure(P>0.05);CDB dose group also had the effect on the cynomolgus monkey of lowering the diastolic blood pressure weekly after administration(P<0.05),low dose CDB group,CDB-PVP group had lower diastolic blood pressure(P>0.05).(2)in terms of platelet count,CDB group showed a platelet inhibition(P<0.05)after the administration in the third and forth week,and CDB-PVP showed it in the forth week,and the other groups did not show the inhibition of platelet function(P>0.05).(3)activated partial thromboplastin time(APTT),CDB high and low dose group,CDB-PVP group had shorter effect on APTT(P<0.05).[Conclusion]1.through the use of cyclodextrins and solid dispersion technology,it was to improve the success of CDB as the representative of Loureirin B in solubility and in vitro dissolution of components.2.effective in improving CDB Loureirin B solubility,solid dispersion had more obvious advantages,but the inclusion of technology to improve the dissolution effect was better.3.The solubility of flavonoids increased after the dragon's blood was inexhaustible in the preparation of the dragon's blood in the form of beta-cd,dragon blood,and the hp-beta-cd and dragon blood.Dragon blood is dissolute in different solvents(p H1.2,2.0,4.0,6.8,7.4 and water).4.CDB could reduce blood pressure in essential hypertension,inhibit platelet aggregation in hypertension,and shorten APTT.5.Improving the solubility of CDB can improve the above-mentioned efficacy,and positively correlated with the dosage. |
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