[Study on mechanism and method of membrane preparation and membrane process optimization based on molecular structure analysis of noneffective common macromolecules].

The molecular weight of the effective components of traditional Chinese medicine( TCM) is usually less than 1 000.However, " noneffective common macromolecules"( starch,pectin and other macromolecules commonly present in the water extract of TCM) generally have no physiological activity,which restricts the overall advantages of membrane technology to obtain small molecular pharmacodynamic substances,and such macromolecules are the main influence factor of membrane fouling. Therefore,in order to obtain the total pharmacological efficacy of TCM,based on the molecular structure analysis of noneffective common macromolecules,aimed at the key scientific problems in correlation between the molecular structure of noneffective common macromolecules and the pore structure of membrane material,and by referring to the material science theory and molecular simulation method,the correlations between noneffective common macromolecules' molecular structure-solution environment-membrane antagonism were investigated. Multidisciplinary approaches could be integrated to: ① optimize the spatial form of membrane surface and improve the membrane's antifouling ability; ② accurately control the pore structure and the size distribution of membranes,aimed at the innovative preparation technology of special membrane used for TCM; ③ adjust solution environment based on the analysis of molecular structure,and establish the pretreatment method based on the optimization of solution environment. Furthermore,the technical bottleneck on how to obtain the pharmacodynamic micromolecules effectively might be solved,and the theory and technology about TCM pharmaceutical engineering could be developed based on the concept of multivariate and integration.

[Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles].

PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration.

[Adsorption characteristics of proteins on membrane surface and effect of protein solution environment on permeation behavior of berberine].

In order to explore the adsorption characteristics of proteins on the membrane surface and the effect of protein solution environment on the permeation behavior of berberine, berberine and proteins were used as the research object to prepare simulated solution. Low field NMR, static adsorption experiment and membrane separation experiment were used to study the interaction between the proteins and ceramic membrane or between the proteins and berberine. The static adsorption capacity of proteins, membrane relative flux, rejection rate of proteins, transmittance rate of berberine and the adsorption rate of proteins and berberine were used as the evaluation index. Meanwhile, the membrane resistance distribution, the particle size distribution and the scanning electron microscope (SEM) were determined to investigate the adsorption characteristics of proteins on ceramic membrane and the effect on membrane separation process of berberine. The results showed that the ceramic membrane could adsorb the proteins and the adsorption model was consistent with Langmuir adsorption model. In simulating the membrane separation process, proteins were the main factor to cause membrane fouling. However, when the concentration of proteins was 1 g•L⁻¹, the proteins had no significant effect on membrane separation process of berberine.

[Preparation and release behaviour of mPEG-PLA α-asarone nanoparticles designed for nasal administration].

Taking α-asarone as model drug, mono methoxy polyethylene glycol-polylactic acid copolymer (mPEG-PLA) as the drug carrier material to prepare drug-loading nanoparticles by premix membrane emulsification for nasal administration. The prepared nanoparticles were spherical with smooth surface and average particle size of 360 nm. Polydispersity index (PDI) was 0. 030, average drug loading of (11.5 ± 0.045) % (n = 3), and the encapsulation efficiency of (86.34 ± 0.11) % (n = 3). X-ray diffraction and differential scanning calorimetry results showed that, α-asarone existed in mPEG-PLA carrier in amorphous or molecular state, different from simple physical mixture. In the in vitro release test in simulated human nasal cavity, α-asarone apis can be released quickly at close to 94% at 102 h, in line with the first-order kinetics (R² = 0.981 9). mPEG-PLA drug-loading nanoparticles release only 54%, with slow release effect, in line with Riger-Peppas model (R² = 0.967 9, n = 0.630 2), for non-fick diffusion, released by the spread of drugs and skeleton dissolution dual control. This provided the foundation for nasal drug delivery in vivo pharmacokinetic study.

[Studies on preparation by SPG membrane emulsification method and in vitro characterization of tetradrine-tashionone II(A)-PLGA composite microspheres].

Tetradrine-tashionone II(A)-PLGA composite microspheres were prepared by the SPG membrane emulsification method, and the characterization of tetradrine-tashionone II(A) -PLGA composite microspheres were studied in this experiment. The results of IR, DSC and XRD showed that teradrine and tashionone II(A) in composite microspheres were highly dispersed in the PLGA with amorphous form. The results of tetradrine-tashionone II(A) -PLGA composite microspheres in vitro release experiment showed that the cumulative release amounts of tetradrine and tashionone II(A) were 6.44% and 3.60% in 24 h, and the cumulative release amounts of tetradrine and tashionone II(A) were 89.02% and 21.24% in 17 d. The process of drug in vitro release accorded with the model of Riger-Peppas. Tetradrine-tashionone II(A) -PLGA composite microspheres had slow-release effect, and it could significantly reduce the burst release, prolong the therapeutic time, decrease the dosage of drugs and provide a new idea and method to prepare traditional Chinese medicine compound.

[Preparation and characterization of tetrandrine-loaded PLGA nanocomposite particles by premix membrane emulsification coupled with spray-drying method].

For effective inhalable dry-powder drug delivery, tetrandrine-PLGA (polylactic-co-glycolic acid) nanocomposite particles have been developed to overcome the disadvantages of nanoparticles and microparticles. The primary nanoparticles were prepared by using premix membrane emulsification method. To prepare second particles, they were spray dried. The final particles were characterized by scanning electron microscopy (SEM), dry laser particle size analysis, high performance liquid chromatography (HPLC), X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared analysis (IR) and confocal laser scanning microscope (CLSM). The average size of the primary particles was (337.5 ± 6.2) nm, while that second particles was (3.675 ± 0.16) µm which can be decomposed into primary nanoparticles in water. And the second particles were solid sphere-like with the drug dispersed as armorphous form in them. It is a reference for components delivery to lung in a new form.

[In vitro and in vivo study of fluorescent probe PLGA particles prepared by premix membrane emulsification method].

Relatively uniform-sized nanoparticles made of poly (lactic-co-glycolic acid) (PLGA) were prepared by premix membrane emulsification method. After the drug loading property was completed, the dynamic tissue distribution of nanoparticles was recorded. With the average particle size and span as indexes, membrane pore size, number of passing membrane times, membrane pressure, volume ratio of oil-water phase and the concentration of poly(vinyl alcohol) (PVA) in external water phase were investigated by single factor test, the optimum preparation technology of blank PLGA nanlparticles was as following: pore size of SPG membrane was 1 µm, membrane pressure was 1. 15 MPa, the number of passing membrane time was 3, the mass fraction of PVA of 2%, volume ratio of oil-water phase of 1 : 5. Prepared nanoparticles were round with smooth surface, the mean diameter was 332.6 nm, span was 0.010, the confocal laser scanning microscope (CLSM) concluded that fluorescent substance is uniform composizion in PLGA nanoparticle, and the in vivo imaging technology in mice include that the nanoparticles show good liver and spleen targeting property.

[Studies on baicalin ethylcellulose microspheres for intranasal administration].

In this study, solvent evaporation method was used to preparing baicalin ethylcellulose microspheres for intranasal administration. The prepared microspheres were round with certain rough surface. The average drug loading and entrapment efficiency was (33. 31 ± 0. 045)% , (63. 34 ± 0. 11)% , respectively. As the characteristic crystalline peaks of baicalin were observed in the microspheres sample, the result of X-ray diffractometric analysis indicated that the baicalin was present in crystalline form after its entrapment in ethylcellulose matrix. By investigating the thermogram of microspheres sample, it was found that endothermic peak of baicalin was shifted from 211. 8 °C to 244. 2 °C and associated with the first broad endothermic peak of ethylcellulose. This could confirm that baicalin was loaded into ethylcellulose, nor simply physical mixture. The powder flowability test exhibited that the specific energy of microspheres was 3. 57 mJ . g-1 and the pressure drop was 2. 22 mBar when air kept the speed of 2 mm . s-1 through the powder bed with the force was 15 kPa. The consequence of the baicalin in vitro released from microspheres showed that the pure baicalin sample displayed faster (90%) release than microspheres sample (75%) in 7 h. Fitting model for release curve before 7 h, the results showed that the pure baicalin sample and the microsphere sample accorded with first order model (R2 = 0. 990 4) and Riger-Peppas model(R2 = 0. 961 2), respectively. Ex vivo rabbit nasal mucosa permeability experiment revealed that the value of cumulative release rate per unit area of the microsphere sample was 1. 56 times that of the pure baicalin sample. This provided the foundation for the in vivo pharmacokinetic study.

[Study of pretreatment on microfiltration of huanglian jiedu decoction with ceramic membranes based on solution environment regulation theory].

To optimize the pretreatment of Huanglian Jiedu decoction before ceramic membranes and verify the effect of different pretreatments in multiple model system existed in Chinese herb aqueous extract. The solution environment of Huanglian Jiedu decoction was adjusted by different pretreatments. The flux of microfiltration, transmittance of the ingredients and removal rate of common polymers were as indicators to study the effect of different solution environment It was found that flocculation had higher stable permeate flux, followed by vacuuming filtration and adjusting pH to 9. The removal rate of common polymers was comparatively high. The removal rate of protein was slightly lower than the simulated solution. The transmittance of index components were higher when adjust pH and flocculation. Membrane blocking resistance was the major factor in membrane fouling. Based on the above indicators, the effect of flocculation was comparatively significant, followed by adjusting pH to 9.

[Optimization theory and practical application of membrane science technology based on resource of traditional Chinese medicine residue].

Resource of traditional Chinese medicine residue is an inevitable choice to form new industries characterized of modem, environmental protection and intensive in the Chinese medicine industry. Based on the analysis of source and the main chemical composition of the herb residue, and for the advantages of membrane science and technology used in the pharmaceutical industry, especially membrane separation technology used in improvement technical reserves of traditional extraction and separation process in the pharmaceutical industry, it is proposed that membrane science and technology is one of the most important choices in technological design of traditional Chinese medicine resource industrialization. Traditional Chinese medicine residue is a very complex material system in composition and character, and scientific and effective "separation" process is the key areas of technology to re-use it. Integrated process can improve the productivity of the target product, enhance the purity of the product in the separation process, and solve many tasks which conventional separation is difficult to achieve. As integrated separation technology has the advantages of simplified process and reduced consumption, which are in line with the trend of the modern pharmaceutical industry, the membrane separation technology can provide a broad platform for integrated process, and membrane separation technology with its integrated technology have broad application prospects in achieving resource and industrialization process of traditional Chinese medicine residue. We discuss the principles, methods and applications practice of effective component resources in herb residue using membrane separation and integrated technology, describe the extraction, separation, concentration and purification application of membrane technology in traditional Chinese medicine residue, and systematically discourse suitability and feasibility of membrane technology in the process of traditional Chinese medicine resource industrialization in this paper.

[Comparative study on four membrane modules in membrane filtration process of Huanglian Jiedu decoction].

OBJECTIVE: To compare the membrane filtration process of four membrane modules namely, FMX rotating disk flat membrane module, hollow fiber membrane module, tubular membrane module and filter cup membrane module, with traditional Chinese medicine compound Huanglian Jiedu decoction as the experimental subject. METHOD: Under the same experimental operating conditions, the four membrane modules in membrane filtration process of Huanglian Jiedu decoction were compared in terms flux, resistance distribution, transmittance of index components and membrane fouling. RESULT AND CONCLUSION: Three membrane modules in the dynamic filtration form--FMX rotating disk flat membrane module, hollow fiber membrane module and tubular membrane module had more advantages than filter cup membrane module in the static dead-end filtration form in terms of permeate flux, transmittance of index components and membrane fouling. However, FMX membrane module that made the fluid in a strong vortex status had better performance than hollow fiber membrane and tubular membrane module in permeate flux and membrane fouling.

[Pollution prevention and control of aqueous extract of astragali radix processed with ZrO2 inorganic ceramic membrane micro-filtration].

OBJECTIVE: To study the measures for preventing and controlling the pollution of aqueous extract of Astragali Radix proceeded with inorganic ceramic membrane micro-filtration, in order to find effective measures for preventing and controlling the membrane pollution. METHOD: The resistance distribution, polymer removal and changes in physical and chemical parameters of the zirconium oxide film of different pore diameters were determined to analyze the state or location of pollutants as well as the regularity of formation. Meanwhile, recoil and ultrasonic physical measures were adopted to strengthen the membrane process, in order to explore the methods for preventing and controlling the membrane pollution. RESULT: When 0.2 microm of ZrO2 micro-filtrated aqueous extract of Astragali Radix, the rate of pollution was as high as 44.9%. The hole blocking resistance and the concentration polarization resistance were the main filtration resistances, while the surface deposit resistance decreased with the increase in the membrane's hold diameter; after micro-filtration, the liquid turbidity significantly reduced, with slight changes in both pH and viscosity. The 0.2 microm ZrO2 micro-filtration membrane performed better than the 0.05 microm pore size membrane in terms of conductivity. The 0. 2 microm and 0.05 microm pore diameter membranes showed better performance in the removal of pectin. The ultrasonic measure to strengthen membranes is more suitable to this system, with a flux rate up by 41.7%. CONCLUSION: The membrane optimization process adopts appropriate measures for preventing and controlling the membrane pollution, in order to reduce the membrane pollution, recover membrane performance and increase filtration efficiency.

[Preparation conditions optimization of Epimedium polysaccharide liposome].

OBJECTIVE: To optimize the preparation conditions of Epimedium polysaccharide liposome (EPSL). METHODS: EPSL was prepared by membrane distribution-supersound method. In preparation of EPSL test, an orthogonal L9 (3(4)) test was used to optimize the preparation conditions, with four factors of ratio of drug to lipid, ratio of lecithin to cholesterol, ultrasonic time and water bath temperature and two indexes of encapsulation efficiency and drug-loading rate. The encapsulation efficiency of EPSL was determined by protamine method. RESULTS: Optimal preparation condition of EPSL was that ratio of drug to lipid, ratio of lecithin to cholesterol, ultrasonic time and water bath temperature were 1: 30, 4: 1,10 min and 40 degrees C respectively. CONCLUSION: EPSL prepared under Optimal conditions has the property of high encapsulation efficiency and drug-loading rate.