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51.
The kinetic equivalency of propylene glycol monomethyl ether (PGME), derived from propylene glycol monomethyl ether acetate (PGMEA), as well as the parent compound (PGME) following intravenous administration to Fischer 344 rats was evaluated. In addition, in vitro hydrolysis rates of PGMEA in blood and liver tissue from rats and humans were determined. The blood kinetics were determined following iv administration to rats of PGME and PGMEA of low [10 and 14.7 mg/kg body weight (bw)] or high (100 and 147 mg/kg) equimolar dosages of PGME and PGMEA, respectively. The blood time courses of PGME elimination for both dosages of both compounds were identical. Half-lives of PGMEA elimination following iv administration of 14.7 or 147 mg PGMEA/kg bw were calculated to be 1.6 and 2.3 min, respectively. Rat and human in vitro hydrolysis rates of PGMEA were determined by incubation of 5 or 50 microg PGMEA/ml in whole blood or liver homogenate. The rate of loss of PGMEA was more rapid in rat blood than in human blood, with hydrolysis half-lives of 36 and 34 min in human blood and 16 and 15 min in rat blood for the 5 and 50 microg/ml concentrations of PGMEA, respectively. In contrast the rate of loss of PGMEA in human and rat liver homogenate incubations was similar, 27-30 min and 34 min, respectively. These data demonstrate the rapid hydrolysis of PGMEA in vivo to its parent glycol ether, PGME and that, once hydrolyzed, the kinetics for PGME derived from PGMEA are identical to that for PGME. This study supports the use of the toxicological database on PGME as a surrogate for PGMEA. 相似文献
52.
Ylva Y. Grams Soile Alaruikka Lisa Lashley Julia Caussin Lynne Whitehead Joke A. Bouwstra 《European journal of pharmaceutical sciences》2003,18(5):329-336
In skin and hair research drug targeting to the hair follicle is of great interest. Therefore the influence of permeant lipophilicity and vehicle composition on local accumulation has been examined using confocal laser scanning microscopy (CLSM). Formulations saturated with either Oregon Green® 488, Bodipy® FL C5 or Bodipy® 564/570 C5 were prepared. The dyes were applied in citric acid buffer, 8% (w/v) surfactants in citric acid buffer or 8% (w/v) surfactants/20% (w/v) propylene glycol in citric acid buffer. Flow-through diffusion experiments were performed with fresh human scalp skin, after which the skin was imaged using CLSM. Diffusion studies showed for Oregon Green® 488 (low lipophilicity) a higher flux when applied in citric acid buffer compared to surfactants. In contrast the fluxes of the more lipophilic dyes (Bodipy® FL C5 and Bodipy® 564/570 C5) are highest when applied in surfactants/propylene glycol. CLSM studies revealed that follicular accumulation increased with (i) a lipophilic dye and (ii) application of lipophilic dyes in surfactants–propylene glycol. Therefore we conclude that targeting to the hair follicle can be increased by the use of lipophilic drugs in combination with surfactant solutions and propylene glycol. 相似文献
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54.
聚乙二醇4000治疗出口梗阻型便秘的临床疗效观察 总被引:1,自引:0,他引:1
目的 评价聚乙二醇 4 0 0 0 (PEG 4 0 0 0 )治疗出口梗阻型便秘 (OOC)的临床疗效。方法 采用随机对照试验方法 ,选择OOC 6 9例 ,随机分为治疗组 (36例 )和对照组 (33例 ) ,分别接受PEG 4 0 0 0和乳果糖治疗 ,疗程 4周并评估其疗效。总体疗效评估采用模拟视觉梯度的评分方法 (1 0 0mmVAS)。结果 治疗 2周和 4周后 ,二组每周排便次数较治疗前均显著增加 ,大便性状、排便困难和直肠排空感均也比治疗前明显改善 (P <0 .0 1 ) ,但二组间差异无显著性 (P <0 .0 5 ) ,其中大便性状改善PEG 4 0 0 0明显优于乳果糖 (P <0 .0 5 )。大便性状恢复正常比例治疗组大于对照组 (治疗 2周和 4周后 ,分别为 75 .0 %和 83.3%比 5 1 .5 %和 6 0 .6 % ,P <0 .0 5 )。PEG 4 0 0 0组 1 0 0mmVAS评分为75 .3,显著高于乳果糖组的 5 4 .8(P <0 .0 5 )。结论 聚乙二醇 4 0 0 0治疗出口梗阻型便秘安全有效 相似文献
55.
开发了二次球磨湿法制备锑掺杂纳米二氧化锡(ATO)/乙二醇(EG)稳定体系的新方法;选用硅烷偶联剂KH 570,实现了ATO颗粒在EG溶液中的均匀分散和稳定性控制;研究了分散工艺参数对体系的影响,探讨了ATO颗粒的表面包覆改性机理。研究表明:分散剂KH 570的含量和体系的pH显著影响ATO在EG中的分散稳定性,在KH 570含量为1.5%,体系pH为8.5时,ATO/EG浆料的分散性能最佳。KH 570与ATO颗粒表面羟基发生的化学键结合,提高了颗粒表面的疏水性,改善了ATO颗粒与有机极性溶剂及高聚物之间的亲和力。 相似文献
56.
57.
分别以单甲氧基聚乙二醇和4臂聚乙二醇引发己酸内酯开环聚合制得线型和星型聚乙二醇-聚己酸内酯(PEG-PCL)两亲嵌段共聚物。IR1、H-NMR和GPC测试结果表明所合成的共聚物具有预期的结构。该PEG-PCL两亲嵌段共聚物中PEG组分具有结晶性。共聚物在水相中自组装形成聚集体,聚集体的水合直径小于50 nm。高浓度共聚物在水性介质中会发生凝胶-溶胶转变,在凝胶-溶胶转变温度以下,共聚物形成凝胶网状结构。共聚物中PEG组分的结晶性、在水相中生成的聚集体的水合直径以及凝胶-溶胶转变行为均与聚合物的组成以及分子形状密切相关。 相似文献
58.
重组L-门冬酰胺酶的聚乙二醇化学修饰及修饰后酶的稳定性研究 总被引:1,自引:0,他引:1
目的单甲氧基聚乙二醇 (mPEG)化学修饰大肠杆菌重组L 门冬酰胺酶 (L ASP) ,考察经过修饰的酶的稳定性。方法N 羟基琥珀酰亚胺 (NHS)活化酯法活化mPEG ,生成的单甲氧基聚乙二醇琥珀酰琥珀酸亚胺酯 (SS mPEG)按不同摩尔比例与L ASP偶联 ,确定适合的反应时间和反应pH值。通过聚乙二醇化学修饰后的酶 (L ASP PEG) ,酶活力和纯度通过奈氏法和丙烯酰胺凝胶电泳 (SDS PAGE)检测 ,高效液相色谱检测L ASP PEG相对分子质量并考察了L ASP PEG体外稳定性等。结果SDS PAGE显示mPEG已经偶联到L ASP分子上 ,以两者摩尔比 1 0∶1为最佳 ,反应pH条件为 8.5 ,获得的L ASP PEG平均比活单位为 6 4 .8IU/mg ,相对分子质量为 30 1 80 0 ,体外稳定性高于L ASP。结论此实验确定了mPEG化学修饰L ASP最佳反应条件为 2 5℃反应 30min ,两者投料摩尔比为 1 0∶1 ,获得的L ASP PEG比L ASP稳定性高 相似文献
59.
George Cruzan Richard A Corley Gordon C Hard Jos J W M Mertens Kenneth E McMartin William M Snellings Ralph Gingell James A Deyo 《Toxicological sciences》2004,81(2):502-511
Ethylene glycol (CAS RN 107-21-1) can cause kidney toxicity via the formation of calcium oxalate crystals in a variety of species, including humans. Numerous repeated dose studies conducted in rats have indicated that male rats are more susceptible than female rats. Furthermore, subchronic and chronic studies using different dietary exposure regimens have indicated that male Wistar rats may be more sensitive to renal toxicity than male Fischer-344 (F-344) rats. This study was conducted to compare the toxicity of ethylene glycol in the two strains of rats under identical exposure conditions and to evaluate the potential contribution of toxicokinetic differences to strain sensitivity. Ethylene glycol was mixed in the diet at concentrations to deliver constant target dosage levels of 0, 50, 150, 500, or 1000 mg/kg/day for 16 weeks to groups of 10 male Wistar and 10 male F-344 rats based on weekly group mean body weights and feed consumption. Kidneys were examined histologically for calcium oxalate crystals and pathology. Samples of blood, urine, and kidneys from satellite animals exposed to 0, 150, 500, or 1000 mg/kg/day for 1 or 16 weeks were analyzed for ethylene glycol, glycolic acid, and oxalic acid. Treatment of Wistar rats at 1000 mg/kg/day resulted in the death of two rats; in addition, at 500 and 1000 mg/kg/day, group mean body weights were decreased compared to control throughout the 16 weeks. In F-344 rats exposed at 1000 mg/kg/day and in Wistar rats receiving 500 and 1000 mg/kg/day, there were lower urine specific gravities, higher urine volumes, and increased absolute and relative kidney weights. In both strains of rats treated at 500 and 1000 mg/kg/day, some or all treated animals had increased calcium oxalate crystals in the kidney tubules and crystal nephropathy. The effect was more severe in Wistar rats than in F-344 rats. Accumulation of oxalic acid in the kidneys of both strains of rats was consistent with the dose-dependent and strain-dependent toxicity. As the nephrotoxicity progressed over the 16 weeks, the clearance of ethylene glycol and its metabolites decreased, exacerbating the toxicity. Benchmark dose analysis indicated a BMDL05 for kidney toxicity in Wistar rats of 71.5 mg/kg/day; nearly fourfold lower than in F-344 rats (285 mg/kg/day). This study confirms that the Wistar rat is more sensitive to ethylene glycol-induced renal toxicity than the F-344 rat and indicates that metabolism or clearance plays a role in the strain differences. 相似文献
60.
Zhi-Yuan Chen He-Song Shen Ming-Yue Luo Chai-Jie Duan Wen-Li Cai Hong-Bing Lu Guo-Peng Zhang Yang Liu Jerome Z Liang 《World journal of gastroenterology : WJG》2013,19(4):561-568
AIM:To evaluate the efficacy of reduced cathartic bowel preparation with 2 L polyethylene glycol(PEG)-4000 electrolyte solution and 10 mg bisacodyl enteric-coated tablets for computed tomographic colonography(CTC).METHODS:Sixty subjects who gave informed consent were randomly assigned to study group A,study group B or the control group.On the day prior to CTC,subjects in study group A were given 20 mL 40% wt/vol barium sulfate suspension before 3 mealtimes,60 mL 60% diatrizoate meglumine diluted in 250 mL water after supper,and 10 mg bisacodyl enteric-coated tablets 1 h before oral administration of 2 L PEG-4000 electrolyte solution.Subjects in study group B were treated identically to those in study group A,with the exception of bisacodyl which was given 1 h after oral PEG-4000.Subjects in the control group were managed using the same strategy as the subjects in study group A,but without administration of bisacodyl.Residual stool and fluid scores,the attenuation value of residual fluid,and discomfort during bowel preparation in the three groups were analyzed statistically.RESULTS:The mean scores for residual stool and fluid in study group A were lower than those in study group B,but the differences were not statistically significant.Subjects in study group A showed greater stool and fluid cleansing ability than the subjects in study group B.The mean scores for residual stool and fluid in study groups A and B were lower than those in the control group,and were significantly different.There was no significant difference in the mean attenuation value of residual fluid between study group A,study group B and the control group.The total discomfort index during bowel preparation was 46,45 and 45 in the three groups,respectively,with no significant difference.CONCLUSION:Administration of 10 mg bisacodyl enteric-coated tablets prior to or after oral administration of 2 L PEG-4000 electrolyte solution enhances stool and fluid cleansing ability,and has no impact on the attenuation value of residual fluid or the discomfor 相似文献