1，2-丙二醇，月桂氮蕈酮—胰岛素传递体经糖尿病小鼠透皮吸收降糖效果研究

目的:研究1,2-丙二醇,月桂氮芯卓酮—胰岛素传递体经皮给药系统对小鼠血糖水平的影响。方法:用超声法制备1,2-丙二醇,月桂氮卓芯酮—胰岛素传递体经皮给药系统,用血糖仪测定血糖含量。对小鼠分别进行了胰岛素传递体和1,2-丙二醇,月桂氮卓芯酮—胰岛素传递体药效学比较。结果:1,2-丙二醇,月桂氮卓芯酮—胰岛素传递体经皮给药系统与胰岛素传递体相比,是其透皮吸收效率的2~3倍,体内药效持续时间也相应延长。2%和6%月桂氮卓芯酮,1,2-丙二醇,—胰岛素传递体经皮给药3h后,小鼠血糖水平分别降为初始值的29.7%和27.9%,5h分别为26.6%和23.7%;腹腔注射胰岛素3h后,小鼠血糖水平降为20.6%,5h后降为33.3%。胰岛素传递体对照组经皮给药3h后,小鼠血糖水平降为75.0%,5h后降为70.3%。结论:1,2-丙二醇,月桂氮卓芯酮—胰岛素传递体经皮给药系统可进一步提高胰岛素传递体的透皮吸收效率,降低血糖。     

月桂氮(艹卓)酮对13种中药的促进透皮吸收作用

目的:讨论月桂氮(艹卓)酮对13种中药的促透皮吸收作用.方法:采用仪器法测定药物在实验模型中的透皮吸收情况及其影响因素.结果:月桂氮(艹卓)酮对13种中药均有显著的促透皮吸收作用.结论:提示月桂氮(艹卓)酮对中药的促透皮吸收作用对中药经皮吸收制剂的开发研究具有重要意义.     

气相色谱法测定月桂氮(艹卓)酮含量

以正廿四烷为内标,在10％SE-30填充柱上直接进行分离,FID检测。本法操作简速,定量准确。     

不同浓度的月桂氮(艹卓)酮对双氯芬酸钠凝胶剂透皮吸收的影响

目的通过动物离体透皮吸收试验,选择双氯芬酸钠凝胶剂中最佳浓度的月桂氮(艹卓)酮(氮酮,Azone)作为渗透促进剂.方法采用改良的Franz扩散装置,以离体鼠皮为屏障、生理盐水为接受介质,研究了不同浓度的月桂氮(艹卓)酮(0%、1%、2%、3%、5%Azone)对双氯芬酸钠凝胶剂透皮吸收的影响.结果双氯芬酸钠凝胶剂12h累积透皮释药百分率依次为38.42%、62.35%、72.80%、32.10%、55.36%.结论 Azone促进双氯芬酸钠凝胶剂透皮释药的最大浓度为2%,筛选出2%月桂氮(艹卓)酮作为促进剂,制备了具有良好经皮吸收性能的双氯芬酸钠凝胶剂.     

月桂氮卓酮促进胰岛素舌下粘膜吸收的研究

研究月桂氮卓酮作为胰岛素舌下粘膜吸收促进剂对正常家兔的降血糖作用,并探讨丙二醇及微晶纤维素的增强促进作用。方法：家兔麻醉后舌下给予 ７Ｕ／ｋｇ胰岛素舌下滴剂,测定给药后 ０、３０、６０、９０、１２０、１５０、１８０、２１０．２４０ｍｉｎ时血糖。结果：与空白对照组相比,含有促进剂的各舌下给药Ⅱ、Ⅲ、Ⅳ组动物血糖的降低率有显著性差异（Ｐ＜０／０５）,其最大降低率分别为３２．６±７．２％、４９．２±４．３％及６５．０±１５．２％,结论：月桂氮卓酮是一种有效的胰岛素舌下粘膜吸收促进剂,在丙二醇和微晶纤维浆的协助下,其促进吸收能力有所增强。     

月桂氮酮促羟乙桂胺透皮吸收的作用

研究了不同浓度的月桂氮(艹卓)酮对肌松药羟乙桂胺大鼠皮肤渗透性的影响。药物累积释放量(Q)、稳态流量(J)、渗透系数(k_p)的计算,表明含不同浓度月桂氮(艹卓)酮的羟乙桂胺乳剂均能增加药物的皮肤渗透性。其 Q 和 J 值与前者的浓度呈正相关。     

月桂氮芯卓酮对青藤碱凝胶剂的透皮吸收作用

目的:考察不同浓度月桂氮(艹卓)酮(azone)对青藤碱凝胶透皮作用的影响,为青藤碱凝胶剂的处方筛选提供依据。方法:采用改良Franz扩散池,以离体大白鼠皮肤为透皮屏障,配制含不同浓度月桂氮(廿卓)酮的青藤碱凝胶,用HPLC法测定青藤碱的透皮吸收量,结果:青藤碱凝胶含2％azone时透皮吸收最好,其体外累积渗透量及促造速率最大。青藤碱凝胶剂的体外渗透药动学符合Higuchi方程。结论:选择2％azone作为青藤碱凝胶剂的促透剂。     

丙二醇,月桂氮Zhou酮对硝酸甘油透皮吸收的影响

采用正交实验设计法研究了不同深度的丙二醇、月桂氮Ｚｈｏｕ酮对到甘油透过兔皮的影响。结果表明,２％丙二醇,１％月桂氮Ｚｈｏｕ酮对硝酸甘油的促进释放作用最好,硝酸甘油累积透皮量与时间呈良好的线性关系。     

月桂氮(艹卓)酮对灭痤乳膏中螺内酯透皮作用研究

目的：研究不同浓度的月桂氮卓酮对灭痤乳膏中螺内酯小鼠离体皮肤渗透性的影响。方法：用改良的Franz扩散池，不同浓度月桂氮卓酮(0、1％、2％和5％)作促渗性试验，采用HPLC法测定和计算药物累积释放量(Q)，稳态流量（J），渗透系数(Kp)。结果：含1％～5％月桂氮卓酮的灭痤乳膏中螺内酯的Q值，较不含月桂氮卓酮者增加了73.66％～74.61％，但各浓度间Q值无显著性差异。结论：1％～5％月桂氮卓酮对灭痤乳膏中螺内酯有明显促渗作用。     

月桂氮(艹卓)酮对替硝唑透皮吸收的作用

目的：本文的研究为临床用药和配制替硝唑（ＴＮＺ）外用药选择适宜药物浓度和促进剂浓度提供依据。方法：观察ＴＮＺ对小白鼠离体皮肤的透皮吸收，比较不同药物浓度的透皮吸收量及月桂氮酮（Ａｚｏｎｅ）不同浓度的促渗作用。结果：０．２％，０．４％，１．０％ＴＮＺ，１２ｈ透皮吸收量分别为１．４１，２．８２，７．１２ｍｇ·（５０ｍｌ）－１，渗透系数分别为１２．９８×１０－６，１３．６８×１０－６，１３．７７×１０－６。促渗剂Ａｚｏｎｅ含量在５％以下时，ＴＮＺ透皮吸收百分率随着Ａｚｏｎｅ浓度的提高而增加；当Ａｚｏｎｅ含量达８％时，透皮吸收率反而下降。结论：ＴＮＺ可透过离体小白鼠皮肤，提高药物浓度可增加药物的透皮吸收量。促渗剂Ａｚｏｎｅ用量以２％～５％为最佳     

Acute, Subchronic, and Chronic Toxicity Studies with Felbamate, 2-Phenyl-1,3-propanediol Dicarbamate

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novelanticonvulsant that is effective against both chemically andelectrically induced seizures in laboratory animals. Acute,subchronic, and chronic studies were conducted in mice, rats,and dogs to establish a preclinical safety profile for thisdrug. Clinical signs following single intraperitoneal dosesincluded hypoactivity, tremors, decreased muscle tone, ataxia,prostration, and labored breathing. Death was observed afterintraperitoneal but not oral administration. A consistent drug-relatedeffect noted in al multiple-dose studies with this compoundwas decreased body weight and food consumption. The only otherconsistent change noted in multiple-dose studies with felbamatewas an increase in liver weight (relative and absolute) in therat and dog which was accompanied in some cases by increasesin serum enzyme levels. No histopathological changes were observedin the liver that could explain these elevated serum enzymelevels. Based on the results of these studies it was concludedthat long-term administration of felbamate in himan clinicaltrials was warranted.     

氮酮和薄荷醇对联苯苄唑体外经皮渗透性的影响

目的：研究透皮促进剂氮酮和薄荷醇对外用抗真菌药联苯苄唑体外经皮渗透性影响。方法：在离体透皮实验装置上进行透皮吸收试验和贮库效应的研究，采用正交函数分光光度法消除皮肤浸出物的吸收干扰。结果：1％氮酮明显促进联苯苄唑经皮渗透作用，并可明显缩短时滞而增加贮库效应。结论：氮酮对亲脂性极强的药物联苯苄唑的促透皮吸收作用较强，而薄荷醇无明显的促透作用，但可增加贮库效应。     

薄荷醇和氮酮对促进甲硝唑透皮吸收作用的比较

通过薄荷醇和氮酮对甲硝唑透皮作用比较,进一步证明薄荷醇确实是一种很有价值的助渗剂,同时也证明甲硝唑在氮酮和薄荷醇助渗下,明显透过离体皮肤,对临床应用甲硝唑作为外用制剂提供依据。     

薄荷醇和氮酮对促进甲硝唑透皮吸收作用的比较

通过薄荷醇和氮酮对甲硝唑透皮作用比较,进一步证明薄荷醇确实是一种很有价值的助渗剂,同时也证明甲硝唑在氮酮和薄荷醇助渗下,明显透过离体皮肤,对临床应用甲硝唑作为外用制剂提供依据。     

Hyperactivity of the dopaminergic system in NTS1 and NTS2 null mice

Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors, NTS1 and NTS2. The functional–anatomical interactions between NT, the mesotelencephalic dopamine system, and structures targeted by dopaminergic projections have been studied. The present study was conducted to determine the effects of NT receptor subtypes on dopaminergic function with the use of mice lacking either NTS1 (NTS1^?/?) or NTS2 (NTS2^?/?). Basal and amphetamine-stimulated locomotor activity was determined. In vivo microdialysis in freely moving mice, coupled with HPLC-ECD, was used to detect basal and d-amphetamine-stimulated striatal extracellular dopamine levels. In vitro radioligand binding and synaptosomal uptake assays for the dopamine transporters were conducted to test for the expression and function of the striatal pre-synaptic dopamine transporter. NTS1^?/? and NTS2^?/? mice had higher baseline locomotor activity and higher basal extracellular dopamine levels in striatum. NTS1^?/? mice showed higher locomotor activity and exaggerated dopamine release in response to d-amphetamine. Both NTS1^?/? and NTS2^?/? mice exhibited lower dopamine D₁ receptor mRNA expression in the striatum relative to wild type mice. Dopamine transporter binding and dopamine reuptake in striatum were not altered. Therefore, lack of either NTS1 or NTS2 alters the dopaminergic system. The possibility that the dysregulation of dopamine transmission might stem from a deficiency in glutamate neurotransmission is discussed. The data strengthen the hypothesis that NT receptors are involved in the pathogenesis of schizophrenia and provide a potential model for the biochemical changes of the disease.     

2-苯基-1,3-丙二醇的制备

2-苯基-1,3-丙醇(1)可用于合成抗癲痫药非氨酯(felbamate)等~([1]).1的合成方法报道很多~([2-5]).其中文献~([2])用2-苯基丙二酸二乙酯(2)经硼氢化钠还原制得1,操作简便,但收率仅48.6%.