胰岛素口腔喷剂临床试验取得成功

由我校药物研究所徐辉碧教授主持研究的治疗糖尿病药物“胰岛素非注射吸收新剂型”——胰岛素口腔喷剂日前在北京协和医院的一期临床试验取得圆满成功.试验证实：胰岛素口腔喷剂不仅适合I型糖尿病患者，对大多数Ⅱ型糖尿病患者也有着非同寻常的意义. 糖尿病的发生主要是由于体内胰岛素绝对缺乏或相对不足引起的.目前，治疗糖尿病最有效最基本的药物就是胰岛素，为提高胰岛素透过率必须选用合适的吸收促进剂，以徐辉碧教授为首的研发人员从化学的角度出发，研究了多肽类大分子透过口腔黏膜的机理，在几十个处方之间进行精心筛选和比较，最终选用了一种无毒、安全、有效的促进剂，研制出了胰岛素口腔喷剂的最佳处方.药品处方经过动物试验阶段，初步试验结果表明，该制剂的生物利用度已达到25％～30％左右，降糖率超过55％. 专家认为，在人体上进行的一期临床试验进一步证明了这种新剂型的效果，胰岛素口腔喷剂正式投入规模生产后，可望为国内糖尿病患者带来福音.     

不同促透剂对马钱子中士的宁透皮吸收的影响

研究不同透皮促进剂对中药马钱子贴剂中士的宁透皮吸收的影响.采用改良Franz扩散池装置,运用HPLC法对士的宁进行含量测定,对不同透皮促进剂的促渗效果进行考察.应用不同质量分数的氮酮、丙二醇、氮酮加丙二醇、冰片为透皮促进剂,士的宁的透皮速率与空白对照组比较,均有提高.对士的宁经皮渗透的促进效果为:5%氮酮丙二醇氮酮+丙二醇冰片.     

鼻粘膜吸收胰岛素的实验研究

胰岛素是胰岛素依赖性糖尿病必不可缺的胰腺激素。数十年来，除了传统的皮下注射或静脉给药途径外，人们还研究了其他给药途径，如口腔、气管、直肠及眼内粘膜给药，以期消除传统途径的弊端。但这些方法用药剂量大而且体内吸收范围波动大，尚无实用价值。近１０几年来，人们发现大分子多肽胰岛素在粘膜吸收促进剂的作用下可经鼻吸收，发挥较好的降血糖作用。对此作者用家兔鼻粘膜进行了胰岛素吸收试验，现报告如下。１　材料和方法　　（１）药物及配制：胰岛素标准品，００２７Ｕ／ｇ，吉林大学分子生物系提供；甘氨胆酸钠，美国Ｓｉｇｍ…     

胰岛素通过电致孔的经皮传输特性

为强化胰岛素在电致孔下的经皮渗透,采用在胰岛素溶液中添加表面活性剂十六烷基三甲基溴化铵(CTAB)的方法,得到了不同聚集程度的胰岛素,研究了胰岛素的聚集程度及供给液的pH值对胰岛素在电致孔下的传质通量和经皮渗透效率的影响。结果表明,胰岛素分子的聚集和其在皮肤中的滞留,是限制胰岛素经皮渗透量提高的主要因素。单体胰岛素分子在脉冲的时间常数为6～8ms时,经皮渗透通量较聚合度接近6的胰岛素提高了3～5倍,且将近70%的胰岛素透过了皮肤。当溶液的pH在4.0～5.0时,胰岛素的经皮渗透通量相对较高。     

尼群地平透皮吸收的研究

利用自制Franz扩散池,测定了含不同透皮吸收促进剂的尼群地平乙醇混悬液离体鼠皮透皮作用,提出了尼群地平的可逆透皮机理,求得了透皮速率常数.实验发现,使用丙三醇、丙二醇作透皮促进剂,使尼群地平的透皮速率常数分别提高了3.73和2.62倍.     

尼莫地平透皮吸收实验中渗透屏障的对比

利用自制Franz扩散池、合成壳聚糖膜及离体鼠皮,测定了含不同透皮吸收促进剂的尼莫地平乙醇混悬液透皮作用,研究了透皮实验初期1 h内的透皮吸收规律,结果表明以合成壳聚糖膜为渗透屏障的实验结果与以离体鼠皮为渗透屏障的实验结果相近似但并不完全相同,壳聚糖膜的结构有待进一步改进.     

右旋布洛芬透皮贴剂的制备

描述了右旋布洛芬透皮贴剂的制备方法,验证了透皮吸收促进剂对右旋布洛芬从贴剂中透皮递送的增强作用,探讨了开发面向骨关节疾病的右旋布洛芬透皮贴剂的可行性.以Eudragit E100为基质制备了右旋布洛芬贴剂,利用HPLC-UV建立并验证了右旋布洛芬及其贴剂的分析方法和质量控制方法.通过SD大鼠腹部皮肤的透皮实验,验证了右旋布洛芬贴剂的透皮递送效果,并对肉豆蔻酸异丙酯、氮酮、异丙醇和油酸等渗透促进剂进行了筛选.结果表明:右旋布洛芬贴剂质量稳定,含量均一度高,可在12 h内实现零级缓释;加入渗透促进剂可增强右旋布洛芬从贴剂中透皮递送能力,其中加入质量分数为2.5%的IPM后,12 h右旋布洛芬累积透过量达(212.37±41.49)μg/cm~2,药物透皮稳态流达(17.70±3.26)μg/(cm~2·h),显著增大了右旋布洛芬的透皮吸收,并优于加入其他促渗剂组(t检验).     

多孔SiO2减反射薄膜的低温制备及光伏应用

采用溶胶凝胶法,使用氨水催化前驱物正硅酸乙酯(TEOS)水解制备SiO2胶体.通过改变溶液浓度调节胶体粒子大小,旋涂低温制备不同折射率纳米多孔SiO2薄膜.使用激光粒度仪和透射电镜分析胶粒大小及分布,粒子分布均匀且在几十纳米范围;使用椭圆偏振仪、紫外/可见分光光度计、扫描电子显微镜表征减反射薄膜的光学性质和表面形貌,发现薄膜表面呈颗粒状且折射率较低,在400nm至800nm波段的透过率平均提高了4%.将溶胶涂在CdS/CdTe太阳电池基底背面,测试结果发现,使用减反射薄膜后电池吸收波段内量子效率(QE)提高,短路电流密度提高了4.45%;光电转换效率由11.50%提高到11.94%.     

不同助剂对铁元素在苹果角质膜渗透的影响

助剂能够促进和提高植物对保护剂、生长调节剂和叶面肥的吸收.为了探讨不同助剂的使用效果,筛选出高效复合型助剂,在25℃和30℃条件下选用磷酸三丁酯(TBP)、癸二酸二乙酯(DES)和辛二酸二乙酯(DESU)三种不同浓度助剂及其不同配方的复合型助剂,进行离体苹果角质膜渗透实验,研究了不同助剂对Fe在角质膜渗透吸收的影响.结果表明:1单一使用不同助剂对Fe的渗透均有促进作用.25℃和30℃时,TBP、DES、DESU的最佳使用质量浓度分别为60、100、300 mg/L和90、120、300 mg/L,其Fe的渗透性大小顺序为DESUTBPDES.2不同配方的复合型助剂对于铁元素在苹果角质膜的渗透作用是不一致的,在25℃和30℃条件下,对Fe的渗透促进作用最佳的分别是TBP(60 mg/L)+DESU(300 mg/L)和TBP(90 mg/L)+DESU(300 mg/L),36 h时Fe的渗透量分别是对照组的4.30和3.19倍.     

促进剂对金属/EPDM黏接的影响

研究了黏合剂中所使用的N 环己基 2 苯并噻唑基次磺酰胺(CZ),N,N 二环己基 2 苯并噻唑基次磺酰胺(DZ),二硫化二苯并噻唑(DM),N,N 间苯撑双马来酰亚胺(PDM)四种不同类型促进剂对黏合剂的影响,以及各促进剂不同用量对黏合剂的影响·实验结果表明,在本实验的黏合剂体系中,促进剂对EPDM橡胶与金属的黏接强度有提高作用,噻唑类促进剂的作用强于酰胺类,最佳促进剂为DM;噻唑类促进剂的最佳质量分数为0 5%,最大剪切强度为1 059MPa·     

冰片对胰岛素透粘膜吸收的促进作用研究

考察冰片对胰岛素透口腔粘膜吸收的促进作用.以SD大鼠为对象,以血糖浓度为指标,研究不同浓度的冰片对胰岛素透口腔粘膜吸收的促进作用.研究发现,一定浓度的冰片(0.12%)能显著促进胰岛素透口腔粘膜的吸收(P<0.05),但由于冰片水溶性极差,其剂量依赖性不很明显,即增加冰片的量不一定能成比例地促进药物的吸收.冰片对胰岛素透口腔粘膜吸收有显著促进作用.     

Lanthanides' enhancing absorption of insulin and reduction of blood glucose of rat by pulmonary administration

To explore the possibility of lanthanides as the enhancer of insulin absorption, the promoting effects of lanthanide ions on the absorption of intrapulmonary delivered insulin and reduction of blood glucose were investigated by means of two approaches, preadministration and coadministration of lanthanide ions with insulin. The results indicate that, compared with the results of those given insulin only, lanthanide ions can effectively enhance the level of insulin and the reduction of glucose level in blood. These effects are dependent on lanthanide species and their concentrations. The mechanism was discussed.     

Lanthanides’ enhancing absorption of insulin and reduction of blood glucose of rat by pulmonary administration

To explore the possibility of lanthanides as the enhancer of insulin absorption, the promoting effects of lanthanide ions on the absorption of intrapulmonary delivered insulin and reduction of blood glucose were investigated by means of two approaches, preadministration and coadministration of lanthanide ions with insulin. The results indicate that, compared with the results of those given insulin only, lanthanide ions can effectively enhance the level of insulin and the reduction of glucose level in blood. These effects are dependent on lanthanide species and their concentrations. The mechanism was discussed.     

猪血及水解母液中氨基酸含量的高效液相色谱分析

以Pico·Tag氨基酸分析法测定了猪血及水解母液中氨基酸含量，猪血中必需氨基酸含量占44．3％，支／芳比值为2.79，有很高的营养价值，其母液中必需氨基酸含量为37．8％，且品种齐全，具有一定的应用价值。样品测定相对标准偏差小于4％。     

胰岛素舌下滴剂促吸收剂的研究

以平均血糖降低百分率和刺激性为参考指标 ,通过SD大鼠分别对 0 .0 7%胰岛素经舌下给药的促吸收剂氮酮、胆酸钠、脱氧胆酸钠和蛋黄卵磷脂进行了实验筛选 .结果表明 ,5 %蛋黄卵磷脂促胰岛素经舌下吸收作用较好 ,且无刺激性     

构造Dn—最优确切设计的偏移调整算法

给出了构造Ｄｎ－最优确切设计的一个新的算法－－偏移调整算法，简称ＥＡＡ算法，并同时给出与Ｗｙｎｎ－Ｍｉｃｈｅｌｌ算法的Ｄ－最优性的比较，证明ＥＡＡ算法有较好的设计效果。     

中国对虾配合饵料化学评价法的研究

本文对中国对虾配合饵料营养价值的化学评价法进行了研究。评价内容包括必需氨基酸指数(EAAI)、蛋白价(PS)、必需氨基酸比例和必需氨基酸供求比。通过各种分析结果及实际投喂试验的比较,认为利用几个化学指标综合评价,能反映饵料的营养价值,而且具有显著的应用价值,方法较简单,省工省时。     

Acetoacetylation of Hydroxyethyl Cellulose

IntroductionSuperabsorbent resin is one of the most importantresins[1] ,but its flexibility is not very good.Somegrafting processes were used to improve theflexibility of superabsorbent resin,for example,acrylate polymer was grafted to hydroxyethylcellulose(HEC) [2 4 ] .Increasing the grafting chainlength increases the flexibility of superabsorbentresin. However,the hydroxyethyl group ofhydroxyethyl cellulose is not very active[5] andwould be more likely to graft if the acetoacetylgroup repl…     

Monomeric insulins obtained by protein engineering and their medical implications

The use of insulin as an injected therapeutic agent for the treatment of diabetes has been one of the outstanding successes of modern medicine. The therapy has, however, had its associated problems, not least because injection of insulin does not lead to normal diurnal concentrations of insulin in the blood. This is especially true at meal times when absorption from subcutaneous tissue is too slow to mimic the normal rapid increments of insulin in the blood. In the neutral solutions used for therapy, insulin is mostly assembled as zinc-containing hexamers and this self-association, which under normal physiological circumstances functions to facilitate proinsulin transport, conversion and intracellular storage, may limit the rate of absorption. We now report that it is possible, by single amino-acid substitutions, to make insulins which are essentially monomeric at pharmaceutical concentrations (0.6 mM) and which have largely preserved their biological activity. These monomeric insulins are absorbed two to three times faster after subcutaneous injection than the present rapid-acting insulins. They are therefore capable of giving diabetic patients a more physiological plasma insulin profile at the time of meal consumption.     

Release of endogenous excitatory amino acids from turtle photoreceptors

Responses to light are transmitted from photoreceptors to second-order retinal neurons by chemical synapses that may use an excitatory amino acid (EAA) as the neurotransmitter. This hypothesis is based primarily on the pharmacological actions of EAA agonists and antagonists on the membrane potentials and light responses of second-order neurons. But the release of endogenous EAAs, which is a critical criterion for the identification of EAAs as transmitters, has not been demonstrated. Here we report the use of outside-out membrane patches excised from rat hippocampal neurons to detect the release of EAAs from synaptic terminals of isolated turtle photoreceptors. Electrical stimulation of or application of lanthanum chloride to photoreceptors induced an increase in the frequency of opening of 50-pS channels in the patches. These channels were identified as the class of glutamate-activated channels that are also gated by aspartate and NMDA (N-methyl-D-aspartate). In several photoreceptor-patch pairs, spontaneous channel activity was observed near the synaptic terminals. These results provide strong evidence to support the hypothesis that both rods and cones of the turtle use an EAA as their neurotransmitter.