Influence of Bile Salts on the Permeability Through the Nasal Mucosa of Rabbits of Insulin in Comparison with Dextran Derivatives

Abstract

The nasal drug absorption and the effect of absorption promoters have been studied in rabbits. Nasal mucosa excised from rabbits was mounted as a flat sheet in an in vitro chamber. The result indicates that the change in the porosity of the membrane by pretreatment with bile salts increased the permeability coefficient of sodium chloride in the nasal membrane. The permeabilities of dextran derivatives were enhanced by pretreatment with sodium glycocholate (GC). The permeability coefficient (P) of fluorescein isothiocyanate diethylaminoethyl dextran     

Effect of Different Bile Salts on the Relative Hypoglycemia of Witepsol W35 Suppositories Containing Insulin in Diabetic Beagle Dogs

Insulin suppositories were formulated using Witepsol W35 as a base to investigate the effect of various bile salts/acids on the plasma glucose concentration of diabetic beagle dogs. Comparison of the effect of these formulations was made with that produced by insulin subcutaneous injections. Of the bile salts/acids studied, incorporation of 100 mg of deoxycholic acid (DCA), sodium cholate (NaC), or sodium deoxycholate (NaDC) with insulin (10 U/Kg) showed that suppositories containing NaDC produced the highest area under the curve (AUC) and relative hypoglycemia (RH) of 290 ± 83 mg%h and 28% ± 8.1%, respectively. To study the optimum amount of NaDC in insulin suppositories to produce the highest RH, 50-200 mg/suppository were used, and we found that 150 mg NaDC produced 35% ± 13% RH. We also studied the influence of different doses of insulin (5-20 U/kg) in the presence of NaDC (100 mg). It was found that increase of the insulin dose was accompanied by an increase in AUC and maximum reduction in plasma glucose level C_max. A combination of NaDC (100 mg) and NaC (50 mg) produced an AUC of 252 ± 13 mg% h and an RH of 49% ± 2.6%, which were higher than produced by either of its individual components (NaC 50 mg or NaDC 100 mg) when used alone or when compared with an equivalent amount of NaDC (150 mg). When the effect of sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC) was studied, it was found that an insulin suppository containing 100 mg of either NaTC or NaTDC produced an RH equivalent to that produced previously with a mixture of NaDC (100 mg) and NaC (50 mg). On the other hand, NaC (50 mg) did not improve the hypoglycemic effect of NaTC any further. In conclusion, a relative hypoglycemia of about 50% can be reached using insulin suppositories containing Witepsol W35 as a base and NaDC plus NaC (100 mg plus 50 mg, respectively), NaTDC (100 mg), or NaTC (100 mg) as rectal absorption enhancers of insulin. A desirable hypoglycemia, expressed as C_max, and/or AUC can be reached by adjusting the insulin dose in the formulation according to the degree of hyperglycemia.     

The Relationship Between the Rigidity of the Liposomal Membrane and the Absorption of Insulin After Nasal Administration of Liposomes Modified with an Enhancer Containing Insulin in Rabbits

The relationship between the rigidity of the liposomal membrane and the absorption of insulin after nasal administration of liposomes modified with an enhancer containing insulin was investigated for the nasal delivery of peptide drugs in rabbits. The rigid liposomal membrane makes liposomes stable, protecting insulin from enzymatic degradation. Soybean-derived sterol (SS) or its sterylglucoside (SG) was used as an enhancer. Dipalmitoylphosphatidylcholine (DPPC) liposomes modified with SG had increased fluidity of the hydrophobic group of the liposome bilayer compared with the liposomes modified with cholesterol (Ch) or SS, as shown by measurements of the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5,-hexatriene (DPH); however, the fluidity of the polar group of the liposome bilayer was decreased according to measurements of steady-state fluorescence anisotropy of dansylhexadecylamine (DSHA) at 37°C. These findings suggest that the fluidity of the hydrophobic group of the liposome bilayer is responsible for the increase of liposomal leakage and instability of the liposomes. When insulin was administered nasally to rabbits as a solution, no hypoglycemic effect was observed. The administration of insulin contained in DPPC/SG (7/4, mole) liposomes with high fluidity caused a high glucose reduction of long duration (8 hr). DPPC/SS and DPPC/Ch (7/4) liposomes with low fluidity caused low glucose reductions. These results demonstrated that liposomes modified with SG can be useful as carriers of insulin administered nasally.     

Influence of pH on the Permeability of p-Toluidine and Aminopyrine Through Shed Snake Skin as a Model Membrane

The influence of pH on the permeability of p-toluidine (pKa, 5.3) and aminopyrine (pKa, 5.0) through shed snake skin as a model membrane was studied. The pH was adjusted to several values, and the solubility of the drugs in each donor was measured. Flux rates and permeability coefficients were calculated from the steady-state penetration portions. The flux rates of p-toluidine decreased as the pH value in the donor solution increased. On the other hand, the flux rates of aminopyrine were constant at any pH value. The permeability coefficients of each drug increased as the pH value in the donor solution increased. The partition coefficients (octanol/buffer) of each drug were dependent on the molecular fraction of un-ionized species. From these results, it is suggested that ionized species of p-toluidine transports through shed snake skin, but the ionized species of aminopyrine does not.     

添加剂对煤沥青在喹啉不溶物滤饼中渗透性的影响

本工作研究了添加剂对煤沥青的渗透性的影响.本研究采用的添加剂是阳离子型和非离子型添加剂的混合体系.它们对煤沥青的粘度和组成的影响很小,但是渗透性却有大幅度提高,根据达西定律和渗透系数方程对煤沥青浸渍动力学进行了讨论,认为添加剂起到了凝聚QI颗粒、增大有效尺寸和增大孔隙率的作用,改变了滤饼结构.随着其含量的增加,渗透性呈现先增加后减小的规律.通过对2D炭预制体致密化发现,添加剂能够提高煤沥青对高密度的预制体的致密化效率.     

Effect of Dimethylacetamide and 2-Pyrrolidone on the Iontophoretic Permeability of LHRH Through Porcine Skin

Abstract

The effect of penetration enhancer (PE) and iontophoresis on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through porcine epidermis 3was investigated. The permeability coefficient of LHRH increased (p < 0.05) through PE (e.g., dimethylacetamide [DMAC] and 2-pyrrolidone [2–P])-treated epidermis. Iontophoresis further increased the permeability of LHRH (p < 0.05) through the PE-pretreated epidermis in comparison to the control (without PEtreated epidermis). This shows that iontophoresis can synergize with PEs such as DMAC and 2-P to provide an additional driving force to maintain and control the target flux of LHRH.     

The Effect of Keratolytic Agents on the Permeability of Three Imidazole Antimycotic Drugs Through the Human Nail

Abstract

The permeability of three imidazole antimycotics (miconazole nitrate, ketoconazole, and itraconazole) through the free edge of healthy human nail was evaluated in vitro using side-by-side diffusion cells. The influence of keratolytic substances (papain, urea, and salicylic acid) on the permeability of the antimycotics was also studied. The results suggested that the nail constituted an impermeable barrier for these antimycotics; it could be considered that the nail behaved as a hydrophilic gel membrane, through which drugs of low solubility could not permeate. The use of ethanol did not promote the passage of any of the antimycotic drugs. Although scanning electron microscopy indicated that the keratolytic substances had a significant effect on the nail surface (papain > salicylic acid > urea), the passage of the three antimycotics was not improved by pretreatment with salicylic acid alone (20% for 10 days), or by the application of the drug in a 40% urea solution. It was found that only the combined effects of papain (15% for 1 day) and salicylic acid (20% for 10 days) were capable of enhancing the permeability of the antimycotic therapeutics. It is conceivable that the enhancement effect can be attributed to the formation of pores which create transport channels, through which the antimycotics are able to permeate.     

中、下承式拱桥吊杆损伤对吊杆系力学性能影响

吊杆作为中、下承式拱桥的重要传力构件,其受力状况与拱桥的安全状况密切相关。由于吊杆只能承受拉力,当吊杆损伤后,吊杆的张力发生改变,同时桥梁的安全状态也会发生变化。基于摄动理论采用三维有限元模型研究吊杆损伤时对吊杆系张力和位移的影响,并以京港澳高速刘江大桥为算例进行证明。计算结果显示吊杆损伤后,损伤吊杆内力降低,但降低比例小于损伤程度;在同片拱肋上其他吊杆张力增加,增加比例随着该吊杆与损伤吊杆间距离的增加而迅速降低,而对侧拱肋上的吊杆内力没有明显的增加。吊杆损伤后,吊杆节点位移变化比例小于损伤程度,且变化比例随着与损伤吊杆间距离的增加而逐步降低。随着吊杆损伤程度的增大,吊杆系内力与吊杆节点位移变化率增加。     

Influence of Certain Additives on the Diffusion Rate of Aspirin, Salicylamide and Phenacetin Through the Rat's Ileum

The diffusion rate of aspirin, salicylamide and phenacetin through the rat's ileum was found to be concentration dependent. The presence of glucoseamine hydrochloride decreased the amount diffused from each drug. The higher diffusion rate of aspirin was happened in presence of 0.01% w/v Myrj 59, followed by Brij 58 and then cetrimide. While that of salicylamide increased in presence of 0.01% w/v Tween 80. The more convenient increase in the diffusion rate of phenacetin produced in presence of 0.01% w/v Tween 20 and 0.3% w/v sodium lauryl sulfate. The other tested surfactants either reduced the amounts of drugs diffused or produced insignificant effect. With regard to the effect of aliphatic acids-drugs solid dispersions, tartaric acid increased the diffusion rate of aspirin; citric, tar taric and succinic acids as well as PEG 4000 increased the diffusion rate of salicylamide while, succinic acid increased the diffusion rate of phenacetin through the rat's ileum.     

The Influence of Vibratory Treatment on the Fatigue Life of Welds: A Comparison with Thermal Stress Relief

Abstract: A comparison has been made between the fatigue lives of welded specimens a) in the as welded condition b) after heat treatment, and c) after post-weld vibration. By comparison with the as-welded specimens, the fatigue lives of the thermally relieved specimens were found to decrease by 43%, while the vibration treated specimens showed an increase of between 17% and 30%. While these findings are interesting in that they offer a way of extending the fatigue lives of welded joints, they confirm the view that the mechanism of residual stress relieving in the vibratory stress relief (VSR) method, and its relationship with fatigue life is poorly understood.     

精子干细胞转染法制备转基因兔的研究

采用直接注射的方法 ,将脂质体包裹的含人乳铁蛋白基因重组质粒 pLNCXHLF注入兔睾丸组织中 ,一个月后与正常雌兔交配。所产仔兔经PCR、Southern检测证明获得了转基因兔 ,转基因阳性率平均为 35 %。实验结果表明 ,通过注射可将外源基因导入到曲细精管中 ,进而完成对精子干细胞的转染 ,获得携带外源基因的成熟精子 ,受精后可得到转基因动物。该方法是一种简捷、有效的新途径 ,既节省时间又降低了成本 ,为利用精子载体制备转基因动物的研究提供了很有价值的参考。     

改进的Gauss-Seidel迭代法对于H-矩阵及其比较矩阵谱半径的影响

本文将改进的Gauss-Seidel迭代法应用于一类有很强应用背景的矩阵-H-矩阵及其比较矩阵,在较目前参考文献更一般的分裂条件下,得到相应的收敛结果及谱半径的比较结果,进而比较了其收敛速度的大小。所用方法不同于以往有关结论,并改进了目前已有相关结论。     

Comparison of in Vitro Release Rates of Nitroglycerin by Diffusion Through a Teflon Membrane to the USP Method

The in vitro release profile of nitroglycerin (GTN) from different transdermal patches through synthetic membranes has been determined and compared to the USP adapted release rate method. Five different nitroglycerin transdermal test formulations were compared to commercially available Nitro-Dur®. All formulations display similar release rate profiles when tested by the USP adapted release rate method. In contrast, significant differences among the tested formulations were observed by using a synthetic Teflon membrane. In these studied an attempt was made to develop a simple, reliable, and reproducible method for testing the release of GTN from different transdermal patches in vitro.     

Comparison of in Vitro Release Rates of Nitroglycerin by Diffusion Through a Teflon Membrane to the USP Method

Abstract

The in vitro release profile of nitroglycerin (GTN) from different transdermal patches through synthetic membranes has been determined and compared to the USP adapted release rate method. Five different nitroglycerin transdermal test formulations were compared to commercially available Nitro-Dur®. All formulations display similar release rate profiles when tested by the USP adapted release rate method. In contrast, significant differences among the tested formulations were observed by using a synthetic Teflon membrane. In these studied an attempt was made to develop a simple, reliable, and reproducible method for testing the release of GTN from different transdermal patches in vitro.     

Effect of Nesting in Laminates on the Through-Thickness Permeability of Woven Fabrics

The layer nesting phenomenon of multilayer fabric has a great influence on the through-thickness permeability, which is a key parameter for the simulation of the through-thickness LCM (Liquid Composite Moldling) processes. In this paper, based on the analyses of the formation reason and characterization parameters of layer nesting, the geometry models of fabric unit-cells with nesting are established. The through-thickness flow in the unit-cell is analyzed to built the governing equations of the resin flow. The inter-yarn and intra-yarn regions of the unit-cell model are discretized uniformly, then the governing equations of the through-thickness flow are numerically solved based on Adams-Bashforth scheme and Chorin projection method, so the through-thickness flow parameters is obtained and the through-thickness permeability of the fabric with nesting can be predicted. The verification of the above method is implemented by comparisons with the available experimental results. A series of simulation experiments are carried out to investigate the nesting behaviors under different layer shifts, and the effects of nesting on the total thickness and through-thickness permeability of woven fabric are researched in detail.     

Effect of Colloidal Carriers on the Disposition and Tissue Uptake of Doxorubicin: I. Conjugation with Oxidized Dextran Particles

Dextrans are water soluble polymers of glucose, with varying molecular weights. The free hydroxyl groups offer attractive sites for conjugation of drugs with the potential for altering the pharmacokinetic profile of the drug. Doxorubicin is a useful anticancer drug with cardiotoxicity as its most serious side effect. This drug was conjugated to dextran in the following manner. A Schiffs base was formed by incubating oxidized dextran (generated using sodium periodate) with doxorubicin. This mixture was then reduced using sodium borohydride. The conjugates, in the size range of 20 nm, were studied in vitro for the maximum uptake and the release of the drug. In vivo, the conjugates showed a markedly altered disposition profile from the control group. The total body clearance of the drug associated with the conjugate decreased. Additionally, lower concentrations of the drug were found in the heart of animals treated with the conjugates indicating the possibility of reduced cardiotoxicity.