Objective:To optimize the extraction process of berberine hydrochloride from Sanhuang Diyu oil by Box-Benhnken re-sponse surface methodology. Methods:The extraction process was optimized with the size of each medicine ( X1 ) , the liquid-solid ra-tio ( X2 ) and the extraction time ( X3 ) as the independent variables and berberine hydrochloride extraction amount ( Y) as the depend-ent variable, and the effects of variables and their interactions on the extraction efficiency were studied. Results:The experiment results indicated that the optimal extraction conditions were as follows:the size of each medicine was 60 meshes, the liquid-solid ratio was 18, and the extraction time was 1. 5 h. Under the above conditions, 3 batches of berberine hydrochloride from Sanhuang Diyu oil were ex-tracted. The average extraction rate of berberine hydrochloride was (16.6 ±0.6) mg·g-1(n =3). Conclusion: The extraction process of Sanhuang Diyu oil optimized by Box-Behnken response surface methodology is simple, stable and predictable.

Objective:To establish a method for the determination of atorvastatin and amlodipine in compound atorvastatin calcium and amlodipine besylate tablets. Methods:The determination was performed on a Gemini-NX C18 column (250 mm × 4. 6 mm, 5μm) with the mobile phase consisting of 20 mmol·L-1 potassium dihydrogen phosphate solution ( adjusting pH to 4 with phosphoric acid)-acetonitrile-methanol (30 ∶10 ∶60) at a flow rate of 1. 0 ml·min-1 . The detection wavelength was set at 240 nm and the column tem-perature was 30℃. The injection volume was 20μl. Results:The linear range of atorvastatine and amlodipine was 0. 4-40. 0μg·ml-1 and 0. 2-20. 0 μg·ml-1, respectively. The mean recovery of atorvastatin and amlodipine was 100. 6% and 99. 7%, and RSD was 0. 92% and 0. 85% (n=9), respectively. Conclusion:The method is special, stable and reliable, and can be used for the content determination of compound atorvastatin calcium and amlodipine besylate tablets.

Objective:To prepare and characterize the PEGylated liposomes containing total saponins of Paris Polyphylla. Meth-ods:Using the size, PDI, zeta potential and encapsulation efficiency of the liposomes as the indicators, the influencing factors in the preparation were optimized. The particle size, PDI and zeta potential were studied by a Malvern Zetasizer, the morphology was ob-served under a TEM, and the stability was studied as well. Results:The particle size, PDI, zeta potential and encapsulation efficiency of the PEGylated liposomes was (109. 4 ± 32. 7) nm, (0. 171 ± 0. 036), ( -36. 7 ± 4. 5) mV and (93. 5 ± 3. 2) %, respectively. The liposomes were small spheres with smooth surface under the TEM. The long term stability studies showed that the liposomes were stable in 3 months after stored at 4℃. Conclusion:The preparation technology of the PEGylated liposomes containing total saponins of Paris Polyphylla is feasible, which can obtain liposomal preparations with high entrapment efficiency and good stability.

Objective:To optimize the ultrasonic-assisted extraction technology of polysaccharide from Tremella by Box-Benhnken response surface methodology .Methods:The single-factor extraction tests and response surface analysis were employed to optimize the technology conditions , including ultrasonic power , ultrasonic time and liquid/solid ratio.Results:The experiment results indicated that the optimal extraction conditions were ultrasonic power of 360 W, ultrasonic time of 23 min and liquid/solid ratio of 45 ∶1 ( ml· g-1 ) . Under the conditions , 6 batches of polysaccharide from Tremella were extracted .The average extraction rate of Tremella polysaccharides was 20.4%±1.8%(n=6).Conclusion: The ultrasonic-assisted extraction process of Tremella polysaccharide using Box-Behnken response surface methodology is simple with good predictability .

Objective: To prepare the total saponins from Paris Polyphylla self-microemulsifying drug delivery system (SMEDDSs) and its solid fied granule, and investigate the in vitro release.Methods: The solubility of the total saponins from Paris Polyphylla in different excipients was investigated.The pseudo-ternary phase diagram composed of different oil phase, emulsifier and co-emulsifier was used to define the self-emulsifying area.The optimal formula of the total saponins from Paris Polyphylla SMEDDSs was prepared into granule.The appearance, morphology, particle size distribution, PdI and zeta potential of the microemulsion and the granule were determined by a dilution method.The drug release profile of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule were compared.Results: The optimal formula of SMEDDSs was as follows: propylene glycol monocaprylate as the oil phase, Tween-80 as the emulsifier and propylene glycol as the co-emulsifier with the optimum ratio of 7.0∶1.5∶1.5.After diluted by water,the total saponins from Paris PolyphyllaSMEDDSs and the granule formed a clear and transparent microemulsion solution with small homogeneous spheres as seen under a transmission electron microscope.The average particle size of the total saponins from Paris Polyphylla SMEDDSs and the granule was (58.6±16.4) nm and (68.1±12.1) nm with PdI of (0.183±0.04) and (0.209±0.05), respectively, and the zeta potential was (-20.2±1.9) mV and (-18.9±1.5) mV, respectively.The results of transmission electron microscopy showed the microemulsion was round, regular and spherical distribution.The in vitro release profile indicated that the accumulated release of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule was more than 85% in 45 min.Conclusion: The self-microemulsifying granule can significantly improve the in vitro dissolution rate of the total saponins from Paris Polyphylla, and the preparation process is simple and feasible.

Objective:To design and develop a formula of solid lipid nanoparticles containing the total saponins of Paris Polyphylla using a quality by design ( QbD) method. Methods:The target product profile of solid lipid nanoparticles was determined according to the properties of dosage form and administration. The risk assessment was carried out according to the theoretical knowledge and experi-ence to define the critical variables influencing the properties of solid lipid nanoparticles. Firstly, Plackett-Burman test was used to screen out the key variables significantly affecting the pharmacological properties of solid lipid nanoparticles, and then the Box-Behnken effect surface method was use to further optimize the selected variables. The physicochemical properties of solid lipid nanoparticles con-taining the total saponins of Paris Polyphylla were studied, such as the particle size distribution, polydispersity index ( PdI) , zeta po-tential, morphology and in vitro drug release behavior. Results: The optimum formula and preparation process were as follows: the concentration of glycerol monostearate was 5. 5％, the concentration of soybean phospholipid was 8. 0％, the number of homogenization was 6 times, the concentration of drug was 5. 0％, the surfactant was Tween 80, the mass pressure was 600 bar and the homogeneous temperature was 65℃. The mean particle size, PdI and zeta potential of the optimized solid lipid nanoparticles was (116. 5 ± 32. 1) nm, (0. 198 ± 0. 018) and ( -23. 6. 5 ± 0. 9) mV, respectively. Transmission electron microscopy showed that the solid lipid nanop-articles were spherical. The results of in vitro release showed a sustained release property, and the cumulative release was 63. 5％ in 24 h. Conclusion:It is feasible to design and develop solid lipid nanoparticles containing the total saponins of Paris Polyphylla by using the QbD method, which can ensure the product quality to meet the requirements.

The aim of this study was to prepare and characterise docetaxel lipid emulsion injection and to conduct the characterization of its pharmacokinetics in rats after tail-vein injection. High pressure homogenization method was used to prepare docetaxel lipid emulsion. 12 Wistar rats were randomly divided into docetaxel lipid emulsion injection group and docetaxel injection group, and dosed at 6 mg/kg through tail-vein injection. Docetaxel concentration in plasma was determined by HPLC. The pharmacokinetic parameters of docetaxel in rats were obtained using the 3P97 program. Particle size, polydispersion index, Zeta potential of docetaxel lipid emulsion were found to be(221. 6±13. 4)nm, (0. 092±0. 003)and -30. 3 mV, respectively. t1/2(α) of docetaxel lipid emulsion injection and docetaxel injection were(0. 072±0. 014)and(0. 066±0. 015)h; t1/2(β) were(0. 573±0. 253)and(0. 432±0. 184)h; AUC0-12 h were(7. 98±1. 25)and(6. 26±1. 83)μg ·h/mL, respectively. Docetaxel lipid emulsion injection had similar pharmacokinetic characteristics to docetaxel injection. The pharmacokinetic data obtained for both preparations fitted a two-compartment model.

Objective:To study the effects of process parameters of fluidized bed granulation on the physical properties of metform-in hydrochloride granule. Methods:The physical properties of metformin hydrochloride were used as the evaluation indices. Single fac-tor experiment was conducted to investigate the influences of equipment factors ( including the nozzle height and the nozzle orifice) and the process parameters ( including binder dosage, inlet air temperature, inlet air flow rate, spray rate and atomization pressure) on the physical prperties. Results: The influences of equipment factors on the physical properties of the granule were not significant. The binder dosage, inlet air temperature, inlet air flow rate, spray rate and atomization pressure showed significant influences on the physi-cal properties of metformin hydrochloride granule. Conclusion:The parameters of fluidized bed granulation process ( binder dosage, in-let air temperature, inlet air flow rate, spray rate and atomization pressure) have significant effects on the physical properties of met-formin hydrochloride granule, which should be controlled according to the requirements of granule properties.

Objective:To optimize the high pressure steaming processing technology for Polygonum multiflorum Thunb.by Box-Behnken response surface methodology , and compare with the traditional processing .Methods:The effects of factors such as steaming temperature, steaming time and drying temperature on polysaccharide content , stilbene glucoside content and normalized value in Po-lygonum multiflorumThunb.were studied by Box-Behnken response surface methodology .The content differences of polysaccharides and stilbene glucoside between the high pressure steaming processed product and the traditional processed product were evaluated .Re-sul ts:The best high pressure steaming processing conditions for Poyl gonumm luitlfo urm Thunb .were as follows:the steaming tempera -ture was 1254.℃ , the steaming time was3.1 h, and the drying temperature was 52℃.The contents of polysaccharides and stilbene glycosides in Polygonum multiflorum Thunb.processed by the high pressure steaming method were 1.24-fold and 5.26-fold higher than those processed by the traditional method .Conclusion:Box-Behnken response surface method can be used to optimize the high pres-sure steaming processing for Polygonum multiflorum Thunb., and the method is simple and predictable .

Objective To study the relationship of different ABO blood types with the risk of cardiovascular events and the severity of CHD.Methods A total of coronary arteriography-confirmed 3823 Chinese Han CHD patients were divided into O blood type group (n=1140) and non-O blood type group (n=2683).A total of 3654 patients who were followed up by telephone for a median period of 24.6 months were divided into cardiovascular events group (n=348) and cardiovascular events-free group (n =3306).The risk of cardiovascular events in CHD patients with different ABO blood types was assessed according to the Cox proportional hazards model.Results The incidence of left main branch lesion or 3-branch lesions was significantly higher in cardiovascular events group than in cardiovascular events-free group (15.2％ vs 8.1％,47.7％ vs 30.5％,P＜0.01).The Gensini score was significantly higher in non-O blood type group than in O blood type group (20 vs 18,P＜0.05).The incidence of cardiovascular events was higher in non-O blood type group than in O blood type group (10.3％ vs 7.8％,P=0.019).Cox proportional hazards model showed that non-O blood type was an risk factor for cardiovascular events (HR =1.318,95 ％CI:1.030-1.685).The risk of cardiovascular events was still higher in non-O blood type group than in O blood type group after adjustment for confounders (HR=1.291,95％CI:1.008-1.657,P=0.046).Conclusion Non-O blood type is closely related with cardiovascular events in Chinese Han CHD patients.