Dendrimer as nanocarrier for drug delivery

Dendrimers are novel three dimensional, hyperbranched globular nanopolymeric architectures. Attractive features like nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery and cavities in the interior distinguish them amongst the available polymers. Applications of dendrimers in a large variety of fields have been explored. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Terminal functionalities provide a platform for conjugation of the drug and targeting moieties. In addition, these peripheral functional groups can be employed to tailor-make the properties of dendrimers, enhancing their versatility. The present review highlights the contribution of dendrimers in the field of nanotechnology with intent to aid the researchers in exploring dendrimers in the field of drug delivery.     

Investigating the chlorination of acidic pharmaceuticals and by-product formation aided by an experimental design methodology

The degradation of seven acidic drugs and two metabolites during chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). A triple-quadrupole (QqQ) system was used to follow the time course of the pharmaceuticals and by-products, while a quadrupole time-of-flight (Q-TOF) system was also used for the identification of the by-products. Under strong chlorination conditions (10 mg/L Cl₂, 24 h), only four of the target compounds were significantly degraded: salicylic acid, naproxen, diclofenac and indomethacine. The degradation kinetics of these four compounds were investigated at different concentrations of chlorine, bromide and pH by means of a Box-Behnken experimental design. Depending on these factors, measured pseudo-first order half-lives were in the ranges: 23-573 h for salicylic acid, 13-446 min for naproxen, 5-328 min for diclofenac and 0.4-13.4 min for indomethacine. Also, it was observed that chlorine concentration was the overall most significant factor, followed by the bromide concentration (except for indomethacine), resulting in increased degradation kinetics as they are increased. The degradation path of salicylic acid, naproxen and diclofenac consisted of aromatic substitution of one or two hydrogens by chlorine and/or bromide. Moreover, for diclofenac, two other by-products corresponding to a decarboxylation/hydroxylation pathway from the monohalogenated products were also identified. On the other hand, indomethacine degradation did not lead to halogenation products but to oxidation ones. The investigation of these by-products in real samples by LC-MS/MS (QqQ) showed that the halogenated derivates of salicylic acid occurred in all the drinking water and wastewater samples analysed.     

舒林酸的合成工艺研究

非甾体抗炎药舒林酸在治疗结肠性息肉和抑制早期癌症方面有良好效果.今介绍舒林酸的改进合成工艺:以对氟氯苄为起始原料,与甲基丙二酸二乙酯缩合,碱性水解,脱羧,SOCl2酰氯化,分子内Friedel-Crafts酰基化、与氰乙酸缩合,水解,与对甲硫基苯甲醛缩合以及氧化反应,制得舒林酸.反应过程中,考察了反应温度,催化剂用量,投料比等对收率的影响,得出最佳反应条件.脱羧反应,温度控制在130～140℃;Friedel-Crafts反应,催化剂无水AlCl3与2-(4-氟苯基)-2-甲基丙二酸的质量比为0.6:1;6-氟-2-甲基茚酮与氰乙酸的缩合反应,催化剂乙酸铵与6-氟-2-甲基茚酮的质量比为0.1:1;5-氟-2-甲基-3-茚乙酸与对甲硫基苯甲醛的缩合反应,5-氟-2-甲基-3-茚乙酸、对甲硫基苯甲醛、甲醇钠的摩尔比为1:1:2.5～4.0;氧化反应,5-氟-2-甲基-1-(4-甲硫基苯亚甲基)-3-茚乙酸与H2O2的质量比为1:0.15.中间体和产品的纯度和结构经气相色谱,气质联用仪,红外光谱及核磁共振仪确定.     

Novel Applications of NSAIDs: Insight and Future Perspectives in Cardiovascular,Neurodegenerative, Diabetes and Cancer Disease Therapy

Once it became clear that inflammation takes place in the modulation of different degenerative disease including neurodegenerative, cardiovascular, diabetes and cancer the researchers has started intensive programs evaluating potential role of non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention or therapy of these diseases. This review discusses the novel mechanism of action of NSAIDs and its potential use in the pharmacotherapy of neurodegenerative, cardiovascular, diabetes and cancer diseases. Many different molecular and cellular factors which are not yet fully understood play an important role in the pathogenesis of inflammation, axonal damage, demyelination, atherosclerosis, carcinogenesis thus further NSAID studies for a new potential indications based on precise pharmacotherapy model are warranted since NSAIDs are a heterogeneous group of medicines with relative different pharmacokinetics and pharmacodynamics profiles. Hopefully the new data from studies will fill in the gap between experimental and clinical results and translate our knowledge into successful disease therapy.     

枕大神经卡压症的临床研究

目的观察药物或局部封闭治疗枕大神经卡压症的疗效。方法对86例枕大神经卡压症的患者先给予药物治疗,疗效差的病例再给予封闭治疗。结果单纯药物治疗的疗效为40.7%,而局部封闭治疗的疗效为90.2%。结论枕大神经卡压症容易误诊,本组病例的误诊率为53.5%;枕大神经卡压症先给予药物治疗,疗效差者给予局部封闭治疗可以获得满意的疗效。     

替普瑞酮对预防非甾体抗炎药相关性溃疡复发的临床研究

目的: 比较长期单独使用替普瑞酮、米索前列醇与奥美拉唑预防非甾体抗炎药(NSAIDs)相关性溃疡复发的疗效和安全性。 方法: 选取107例长期应用NSAIDs所致消化性溃疡的患者,经6～8周的治疗溃疡愈合后,随机分为:替普瑞酮组(38例),长期服用替普瑞酮50 mg/次,3次/d;奥美拉唑组(35例),长期服用奥美拉唑 20 mg/次,2次/d;米索前列醇组(34例),长期服用米索前列醇 200 μg/次,2次/d;疗程共52周,分别观察和比较3组患者第0～26、27～52周期间溃疡的复发率和不良反应的发生率。 结果: 第0～26周期间替普瑞酮组、米索前列醇组与奥美拉唑组患者溃疡复发人数分别为5(13.2%)、5(14.3%)、4(11.8%)例,经比较各组间差异无统计学意义(P＞0.05);第27～52周期间3组患者溃疡复发人数分别为6(18.2%)、3(10.0%)、4(13.3%)例,经比较各组间差异无统计学意义(P＞0.05)。第0～26周期间3组患者发生不良反应的人数分别为5(13.2%)、4(11.4%)、12(35.3%)例,经比较替普瑞酮与奥美拉唑组组间差异无统计学意义(P＞0.05),米索前列醇组显著高于其它两组 (P＜0.05);第27～52周期间3组发生不良反应的人数分别为3(9.1%)、9(30.0%)、10(33.3%)例,经比较奥美拉唑与米索前列醇组显著高于替普瑞酮组(P＜0.05)。 结论: 应用替普瑞酮可显著降低NSAIDs相关性溃疡复发,与长期使用米索前列醇和质子泵抑制剂(PPI)类药物的疗效相同,但相关药物并发症的发生显著减少。     

普拉洛芬的合成研究改进

以2-氯烟酸为原料,在强碱环境下与苯酚缩合,然后通过多聚磷酸脱水,硼氢化钾还原,再经过酸性水解,最后与氯乙酰氯进行酰化反应后,在碱性条件下发生水解反应,经磺酰氯酰化,最终通过重排得到普拉洛芬。此工艺不仅避免使用氯化锌和氰化钾,同时也减少了副反应,总收率23．7％,工艺稳定可行。     

Potential Targets for Colorectal Cancer Prevention

The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.