Proteins and peptides(PPs)have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy,but fewer side effects.Owing to the poor stability and limite...Proteins and peptides(PPs)have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy,but fewer side effects.Owing to the poor stability and limited permeability through gastrointestinal(GI)tract and epithelia,the therapeutic PPs are usually administered by parenteral route.Given the big demand for oral administration in clinical use,a variety of researches focused on developing new technologies to overcome GI barriers of PPs,such as enteric coating,enzyme inhibitors,permeation enhancers,nanoparticles,as well as intestinal microdevices.Some new technologies have been developed under clinical trials and even on the market.This review summarizes the history,the physiological barriers and the overcoming approaches,current clinical and preclinical technologies,and future prospects of oral delivery of PPs.展开更多
Dual-phase membranes of 60 wt% Ce0.8Gd0.2O2-δ-40 wt% Pr Ba Co2exFexO3 d（0 x 2） were prepared by a combined citrate and ethylene diamine tetraacetic acid（EDTA） complexing method. X-ray diffraction（XRD）results re...Dual-phase membranes of 60 wt% Ce0.8Gd0.2O2-δ-40 wt% Pr Ba Co2exFexO3 d（0 x 2） were prepared by a combined citrate and ethylene diamine tetraacetic acid（EDTA） complexing method. X-ray diffraction（XRD）results revealed the good chemical compatibility between ion-conducting phase CGO and electron-conducting phases PBC2 xFxO after sintering in air. The Fe ionic dopant had a significant effect on the phase structure stability and oxygen permeability under CO2 atmosphere, which was confirmed by XRD, thermogravimetrye differential scanning calorimetry（TGeD SC）, scanning electron microscopy（SEM） and oxygen permeation experiments. CGOeP BC0.5F1.5O dual-phase membrane demonstrated a stable oxygen permeation flux of2.71x10-7mol cm 2s 1with 50 mol% He/CO2 as the sweep gas at 925 C, and this value was much higher than that of perovskite-type membranes. The rate-limiting step in the oxygen permeation process changed from the bulk diffusion to the surface oxygen exchange when the CGOeP BC0.5F1.5O membrane thickness decreased to 0.8 mm or less. Due to the high oxygen permeation fluxes and the excellent structural stability under CO2 atmosphere, the CGOeP BC0.5F1.5O membrane is a great potential candidate material for separating oxygen from air in the oxy-fuel combustion techniques.展开更多
Mixed oxygen-ionic and electronic conducting membranes of SrFe（Cu）O3-δ were prepared by solid-state reaction method. The crystal structure, oxygen nonstoichiometry, and phase stability of the materials were studied...Mixed oxygen-ionic and electronic conducting membranes of SrFe（Cu）O3-δ were prepared by solid-state reaction method. The crystal structure, oxygen nonstoichiometry, and phase stability of the materials were studied by TGA and XRD. Oxygen permeation fluxes through these membranes were studied at operating temperature ranging from 750 to 950 ℃. Results showed that doping Cu in SrFeO3-δ compound had a significant effect on the formation of single-phased perovskite structure. For SrFe1-xCu2O3-δ series materials, the oxygen nonstoichiometry and the oxygen permeation flux increased considerably with the increase of Cu-doping content （x = 0.1-0.3）. The sintering property of the membrane decreased significantly when the Cu substitution amount reached 40%. SrFe0.7Cu0.3O3-δ showed high oxygen permeation flux, but SrCuO2 and Sr2Fe2O5 phases formed in the compound after oxygen permeation test induced cracks in the membrane.展开更多
Ba0.9R0.1Co0.TFe0.225Ta0.07503-δ （BRCFT, R = Ca, La or Sr） membranes were synthesized by a solid-state reaction. Metal cation Ca2＋, La3＋ or Sr2＋ doping on A-site partially substituted Ba2＋ in BaCoo.TFe0.225Ta0....Ba0.9R0.1Co0.TFe0.225Ta0.07503-δ （BRCFT, R = Ca, La or Sr） membranes were synthesized by a solid-state reaction. Metal cation Ca2＋, La3＋ or Sr2＋ doping on A-site partially substituted Ba2＋ in BaCoo.TFe0.225Ta0.07503-δ oxides, and its subsequent effects on phase structure stability, oxygen permeability and oxygen desorption were systematically investigated by XRD, TG-DSC, Hz-TPR, O2-TPD techniques and oxygen permeation experiments. The partial substitution with Ca2＋, La3＋ or Sr2＋, whose ionic radii are smaller than that of Ba2＋, succeeded in stabilizing the cubic perovskite structure without formation of impurity phases, as revealed by XRD analysis. Oxygen-involving experi- ments showed that BRCFT with A-site fully occupied by Ba2＋ exhibited good oxygen permeation flux under He flow, reaching about 2.3 mL.min-l .cm-2 at 900 with I mm thickness. Of all the membranes, BLCFT membrane showed better chemical stability in CO2, owing to the reduction in alkalinity of the mixed conductor oxide by La doping. In addition, we also found the stability of the perovskite structure under reducing atmospheres was strengthened by increasing the size of A-site cation （Ba2＋〉La3＋〉SrZ＋〉Ca2＋）.展开更多
Perovskite type SrCo0.4Fe0.6O3-δ(SCF) membrane and a novel perovskite-related ZrO2 doped SrCo0.4Fe0.6O3-δ(SCFZ) membrane were successfully prepared by isostatic pressing. The sintered membranes were characterized b...Perovskite type SrCo0.4Fe0.6O3-δ(SCF) membrane and a novel perovskite-related ZrO2 doped SrCo0.4Fe0.6O3-δ(SCFZ) membrane were successfully prepared by isostatic pressing. The sintered membranes were characterized by high-temperature X-ray diffraction (HTXRD) and energy dispersive spectroscopy (EDS). The oxygen permeabilities of membranes have been measured in the temperature range of 923 K to 1243 K. The oxygen permeation flux at 1123K and activation energy of SCFZ membrane with the thickness of 2mm are respectively 2.68×10^-7 mol·cm^-2·min^-1 and 97.76 kJ·mol^-1. The results of HTXRD in argon atmosphere and the oxygen permeation experiment indicate that the SCFZ membrane is stable at elevated temperature and low oxygen partial pressure.展开更多
SrxBi1-xFeO3- (SBF) series mixed conductors were synthesized using Standard ceramic method. The properties of such materials were characterized by XRD, O2-TPD techniques. Ab-normal crystal phenomena were found and exp...SrxBi1-xFeO3- (SBF) series mixed conductors were synthesized using Standard ceramic method. The properties of such materials were characterized by XRD, O2-TPD techniques. Ab-normal crystal phenomena were found and explained and correlated with the oxygen permeation results. By analysis of the critical radius (rc), the degree of openness of the lattice (Fv) and the average metal-oxygen bonding energy of the perovskite lattice (ABE), it was proposed that the oxygen permeation flux is determined mainly by the oxygen diffusion rate in bulk when 1-x≤0.5, and by the concentration of oxygen vacancy when 1-x≥ 0.5. The stability of Sr0.5Bi0.5FeO3- was also investigated, and the high stability of it was attributed to the stable BO6 octahedra.展开更多
For the production of reactive polyurethane cross-linkinger and curing agents, 2, 4-diisocyanate toluene （TDI） terpolymer, which possesses the rigid structures of hexatomic ring and three reactive functional groups,...For the production of reactive polyurethane cross-linkinger and curing agents, 2, 4-diisocyanate toluene （TDI） terpolymer, which possesses the rigid structures of hexatomic ring and three reactive functional groups, was synthesized and characterized by the Fourier transform infrared （FFIR）, the gel permeation chromatography （GPC） and the chemical analysis methods. The reaction conditions were studied and optimized. A tracking research on the polymerization process of TDI was taken by using the GPC. The formation processes of the terpolymer, oligomers and higher-polymers were also dealt with. Results show that the TDI terpolymer can be prepared in the presence of Cat-3 catalyst and at the reaction temperature of （60 ±2）℃. The reaction time is short, its outcomes have narrow molecular weights distribution, namely molecular weights from 530 to 550, Mw/Mn =1.10, and the mass fraction of NCO is （25. 0 ± 0. 5）%. With the reaction time prolonging, however, TDI can be further higher-polymedzed to form higher-polymers. Benzoyl chloride （0. 4%, mass fraction）, as the stabilizing agent, can effectively inhibit the occurrence of higher-polymerization. The obtained TDI terpolymer can be stable for more than half a year.展开更多
基金financially supported by National Natural Science Foundation of China(No.s 81872815,81872826 and 82073801)Science and Technology Commission of Shanghai Municipality(No.18ZR1404100,China)+1 种基金Shanghai Pujiang Program(No.18PJD001,China)Key Subject of Shanghai Skin Disease Hospital(No.2019ZDXK03,China)
文摘Proteins and peptides(PPs)have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy,but fewer side effects.Owing to the poor stability and limited permeability through gastrointestinal(GI)tract and epithelia,the therapeutic PPs are usually administered by parenteral route.Given the big demand for oral administration in clinical use,a variety of researches focused on developing new technologies to overcome GI barriers of PPs,such as enteric coating,enzyme inhibitors,permeation enhancers,nanoparticles,as well as intestinal microdevices.Some new technologies have been developed under clinical trials and even on the market.This review summarizes the history,the physiological barriers and the overcoming approaches,current clinical and preclinical technologies,and future prospects of oral delivery of PPs.
基金supported by the National Natural Science Foundation of China (Nos. 51004069 and 51474145)the National Science Fund for Distinguished Young Scholars (No. 51225401)the Innovation Program of Shanghai Municipal Education Commission and Shanghai University (Nos. 14YZ013 and SDCX2012002)
文摘Dual-phase membranes of 60 wt% Ce0.8Gd0.2O2-δ-40 wt% Pr Ba Co2exFexO3 d（0 x 2） were prepared by a combined citrate and ethylene diamine tetraacetic acid（EDTA） complexing method. X-ray diffraction（XRD）results revealed the good chemical compatibility between ion-conducting phase CGO and electron-conducting phases PBC2 xFxO after sintering in air. The Fe ionic dopant had a significant effect on the phase structure stability and oxygen permeability under CO2 atmosphere, which was confirmed by XRD, thermogravimetrye differential scanning calorimetry（TGeD SC）, scanning electron microscopy（SEM） and oxygen permeation experiments. CGOeP BC0.5F1.5O dual-phase membrane demonstrated a stable oxygen permeation flux of2.71x10-7mol cm 2s 1with 50 mol% He/CO2 as the sweep gas at 925 C, and this value was much higher than that of perovskite-type membranes. The rate-limiting step in the oxygen permeation process changed from the bulk diffusion to the surface oxygen exchange when the CGOeP BC0.5F1.5O membrane thickness decreased to 0.8 mm or less. Due to the high oxygen permeation fluxes and the excellent structural stability under CO2 atmosphere, the CGOeP BC0.5F1.5O membrane is a great potential candidate material for separating oxygen from air in the oxy-fuel combustion techniques.
基金Natural Science Foundation of Guangdong Province (No. 030514)the Science and Technology Program of Guangdong Province(No. 2004B33401006)
文摘Mixed oxygen-ionic and electronic conducting membranes of SrFe（Cu）O3-δ were prepared by solid-state reaction method. The crystal structure, oxygen nonstoichiometry, and phase stability of the materials were studied by TGA and XRD. Oxygen permeation fluxes through these membranes were studied at operating temperature ranging from 750 to 950 ℃. Results showed that doping Cu in SrFeO3-δ compound had a significant effect on the formation of single-phased perovskite structure. For SrFe1-xCu2O3-δ series materials, the oxygen nonstoichiometry and the oxygen permeation flux increased considerably with the increase of Cu-doping content （x = 0.1-0.3）. The sintering property of the membrane decreased significantly when the Cu substitution amount reached 40%. SrFe0.7Cu0.3O3-δ showed high oxygen permeation flux, but SrCuO2 and Sr2Fe2O5 phases formed in the compound after oxygen permeation test induced cracks in the membrane.
基金supported by the National Natural Science Foundation of China(51004069)the National Science Fund for Distinguished Young Scholars(51225401)+1 种基金China Postdoctoral Science Foundation(201104254)the Innovation Program of Shanghai Municipal Education Commission and Shanghai University(14YZ013 and SDCX2012002)
文摘Ba0.9R0.1Co0.TFe0.225Ta0.07503-δ （BRCFT, R = Ca, La or Sr） membranes were synthesized by a solid-state reaction. Metal cation Ca2＋, La3＋ or Sr2＋ doping on A-site partially substituted Ba2＋ in BaCoo.TFe0.225Ta0.07503-δ oxides, and its subsequent effects on phase structure stability, oxygen permeability and oxygen desorption were systematically investigated by XRD, TG-DSC, Hz-TPR, O2-TPD techniques and oxygen permeation experiments. The partial substitution with Ca2＋, La3＋ or Sr2＋, whose ionic radii are smaller than that of Ba2＋, succeeded in stabilizing the cubic perovskite structure without formation of impurity phases, as revealed by XRD analysis. Oxygen-involving experi- ments showed that BRCFT with A-site fully occupied by Ba2＋ exhibited good oxygen permeation flux under He flow, reaching about 2.3 mL.min-l .cm-2 at 900 with I mm thickness. Of all the membranes, BLCFT membrane showed better chemical stability in CO2, owing to the reduction in alkalinity of the mixed conductor oxide by La doping. In addition, we also found the stability of the perovskite structure under reducing atmospheres was strengthened by increasing the size of A-site cation （Ba2＋〉La3＋〉SrZ＋〉Ca2＋）.
基金Supported by the National Advanced Materials Committee of China(No.715-006-0120)and the National Natural Science Foundation of China(No.59789201).
文摘Perovskite type SrCo0.4Fe0.6O3-δ(SCF) membrane and a novel perovskite-related ZrO2 doped SrCo0.4Fe0.6O3-δ(SCFZ) membrane were successfully prepared by isostatic pressing. The sintered membranes were characterized by high-temperature X-ray diffraction (HTXRD) and energy dispersive spectroscopy (EDS). The oxygen permeabilities of membranes have been measured in the temperature range of 923 K to 1243 K. The oxygen permeation flux at 1123K and activation energy of SCFZ membrane with the thickness of 2mm are respectively 2.68×10^-7 mol·cm^-2·min^-1 and 97.76 kJ·mol^-1. The results of HTXRD in argon atmosphere and the oxygen permeation experiment indicate that the SCFZ membrane is stable at elevated temperature and low oxygen partial pressure.
文摘SrxBi1-xFeO3- (SBF) series mixed conductors were synthesized using Standard ceramic method. The properties of such materials were characterized by XRD, O2-TPD techniques. Ab-normal crystal phenomena were found and explained and correlated with the oxygen permeation results. By analysis of the critical radius (rc), the degree of openness of the lattice (Fv) and the average metal-oxygen bonding energy of the perovskite lattice (ABE), it was proposed that the oxygen permeation flux is determined mainly by the oxygen diffusion rate in bulk when 1-x≤0.5, and by the concentration of oxygen vacancy when 1-x≥ 0.5. The stability of Sr0.5Bi0.5FeO3- was also investigated, and the high stability of it was attributed to the stable BO6 octahedra.
文摘For the production of reactive polyurethane cross-linkinger and curing agents, 2, 4-diisocyanate toluene （TDI） terpolymer, which possesses the rigid structures of hexatomic ring and three reactive functional groups, was synthesized and characterized by the Fourier transform infrared （FFIR）, the gel permeation chromatography （GPC） and the chemical analysis methods. The reaction conditions were studied and optimized. A tracking research on the polymerization process of TDI was taken by using the GPC. The formation processes of the terpolymer, oligomers and higher-polymers were also dealt with. Results show that the TDI terpolymer can be prepared in the presence of Cat-3 catalyst and at the reaction temperature of （60 ±2）℃. The reaction time is short, its outcomes have narrow molecular weights distribution, namely molecular weights from 530 to 550, Mw/Mn =1.10, and the mass fraction of NCO is （25. 0 ± 0. 5）%. With the reaction time prolonging, however, TDI can be further higher-polymedzed to form higher-polymers. Benzoyl chloride （0. 4%, mass fraction）, as the stabilizing agent, can effectively inhibit the occurrence of higher-polymerization. The obtained TDI terpolymer can be stable for more than half a year.
