用三角相图法研究药用微乳的形成条件

目的　用建立的改良三角相图法制备低毒药用微乳。方法　选磷脂和聚氧乙烯辛基苯基醚(OP)为乳化剂,乙醇和正辛醇为助乳化剂,油酸乙酯和橄榄油为油相,以改良三角相图法即固定水相和助乳化剂的比值(W/A)或油相和助乳化剂的比值(O/A),对比经典三角相图法即固定乳化剂和助乳化剂的比值(K_m)制备的微乳所需乳化剂和助乳化剂的量及相体积比的大小。结果　对磷脂为乳化剂形成的微乳系统,改良三角相图法所需乳化剂的量为6%-28%,而经典三角相图法所需乳化剂的量为28%-29.6%。对OP为乳化剂形成的微乳系统,改良三角相图法所需乳化剂为23%-40%;而经典三角相图法所需乳化剂为27.6%-49.8%,以上两种系统,前者均较后者用量小。结论　用改良三角相图代替经典三角相图研究形成药用微乳的理论,对寻找低毒性的微乳有积极的指导意义。     

伪三元相图法研究芦丁自微乳化释药系统的制备工艺

摘 要 目的：应用伪三元相图法优化芦丁自微乳化释药体系的处方构成。 方法: 对油相、乳化剂、助乳化剂通过溶解度试验进行初步筛选,应用水滴定法绘制伪三元相图,考察不同配方的相图行为,确定芦丁的最佳自微乳处方构成。 结果: 优化的芦丁自微乳化释药系统的处方组成为油酸 聚氧乙烯40氢化蓖麻油 无水乙醇,质量比为23∶36∶12,制备的自微乳和载药微乳澄清透明。 结论:由伪三元相图法筛选的处方制备而成的自微乳化释药系统能显著提高芦丁的溶解度。     

胸腺五肽油包水型口服微乳的处方设计与评价

目的对胸腺五肽油包水(W/O)型口服微乳进行处方设计及评价。方法 Km值(Km=m乳化剂∶m助乳化剂)滴定法制备伪三元相图,考察油相、乳化剂、助乳化剂、Km值、温度和药物对W/O微乳区域面积和载水量的影响,求出W/O型微乳的最佳处方组合。结果物理化学性质稳定且W/O区域面积和载水量均较高的W/O型微乳的最佳处方组合为蒸馏水/豆磷脂/无水乙醇/辛癸酸三甘油酯(Km=1∶1),制备温度为室温(20±1)℃。根据最佳处方组合,将水溶性药物胸腺五肽溶于水相中,制备了含药微乳的伪三元相图。结论蒸馏水/豆磷脂/无水乙醇/辛癸酸三甘油酯(Km=1∶1)组合具有较大W/O区域面积和载水量,可成功地将水溶性肽类药物包载于水相,并可将其应用于口服药物传递载体。     

卵磷脂微乳的制备与理化性质考察

目的：对25℃各卵磷脂系统中微乳的形成区域以及微乳理化性质随系统中各组分的变化情况进行研究。方法：卵磷脂作表面活性剂,短链醇类作助表面活性剂,采用不同油相考察相图中油包水型微乳形成区域的变化;选择不同处方组分的微乳测定微乳理化性质。结果：各个系统均可形成油包水型微乳,室温下放置数月未见分层。卵磷脂/醇质量比(K_m)与水相量对微乳的粘度有显著影响;电导率随着水相含量增加而增大;微乳的粒径随着体系中水相的增加而增大。结论：K_m较大,水相含量适中的微乳体系较为适合制备药物载体。     

反相微乳制备的影响因素考察及处方优化

目的:考察油相、乳化剂和药物对反相微乳形成的影响。方法:采用伪三元相图法,考察乳化剂为司盘-80/吐温-80,模型药为胸腺五肽,油相为长链甘油酯、中链甘油酯、非甘油酯等各因素不同组成对反相微乳形成的影响,筛选最优处方。结果:以中链甘油酯为油相制得的反相微乳具有最大的W/O区域面积;确定最终处方为蒸馏水/司盘-80/吐温-80/辛癸酸三甘油酯(2∶3∶6∶9),胸腺五肽溶于水相中较宜。结论:乳化剂及油相组成、药物均对反相微乳的形成有影响,实际制备中应对各因素水平进行优化。     

棕榈氯霉素卵磷脂O/W型微乳制剂的研究

目的 棕榈氯霉素卵磷脂O/W型微乳制剂的制备与含量检测。方法 用十六酸异丙酯溶解棕榈氯霉素作油相,卵磷脂和吐温₈₀混合作为表面活性剂,乙醇为助表面活性剂,制备O/W型微乳制剂;用高效液相色谱法进行棕榈氯霉素含量的测定。色谱条件:C₁₈柱(250 mm×4.60 mm,5μm),流动相为甲醇液,柱温25℃,流量为1.0 ml·min^-1,检测波长为271 nm,进样体积20μl。结果 取得了较好的棕榈氯霉素卵磷脂O/W型微乳制剂及较好的含量检测方法。讨论 棕榈氯霉素可以制成卵磷脂O/W型微乳制剂,用高效液相色谱法进行含量测定。     

伪三元相图法优化复方丁香油微乳制备工艺

目的应用伪三元相图法优化复方丁香油微乳的处方工艺。方法以复方丁香油为油相,蒸馏水为水相,强力搅拌,借助伪三元相图,比较微乳区域大小,以选择合适的乳化剂和助乳化剂,并确定其最佳配比。结果吐温类作乳化剂的效果明显优于司盘类,且随着吐温类其分子量的增大乳化效果也增强;助乳化剂宜选用醇类;按适当配比可制得透明均一的复方丁香油微乳。结论以吐温-80为乳化剂,1,2-丙二醇为助乳化剂,复方丁香油为油相,按6∶2∶2的比例制得复方丁香油微乳的性质最好。     

以油包水型微乳为载体促进氟尿嘧啶的经皮渗透

以磺化琥珀酸二辛酯钠 (AOT) 为主要表面活性剂,制备氟尿嘧啶油包水型微乳制剂,以促进药物的经皮渗透。以伪三元相图为基础,依据微乳区域大小, 初步筛选微乳处方;用改进的Franz扩散池和离体小鼠皮肤研究氟尿嘧啶的透皮速率,以单位面积的透皮累积渗透量 (Q_n) 为指标, 考察微乳处方中助表面活性剂的种类、水相比例、混合表面活性剂比例、表面活性剂和助表面活性剂质量比和载药量对离体鼠皮透皮吸收的影响, 优化处方。结果表明,氟尿嘧啶微乳的优化处方为含药0.5%（w/v）,水30%,混合表面活性剂（AOT/Tween 85, K_m = 2）20%, 油相（IPM）49.5%,经皮渗透符合一级速率方程,12 h累积渗透量为（1 355.5 ± 41.1）μg·cm^-2, 分别为0.5%药物水溶液和2.5%（w/w）市售乳膏（O/W）的19.1和7倍。水/AOT/Tween 85/IPM微乳系统能促进5-氟尿嘧啶的透皮吸收, 可以作为氟尿嘧啶等亲水性但水溶性差和渗透性差的药物的新型经皮给药载体。

     

低毒药用微乳的研制

目的 用较少量的乳化剂和辅助乳化剂制备微乳．以减少药用微乳的毒性。方法 由花生油、水、吐温-80组成三相(油相、水相、乳化剂)．再分别加辅助剂和不加辅助剂制备O／W型微乳；通过采用改良三角相图法．比较各处方中乳化剂和辅助剂的使用量(B)。结果 单独以乳化剂吐温-80制备微乳．消耗的乳化剂量较大；而加入辅助剂制备微乳．能明显降低B值．其中以加入平平加O为辅助剂的B值最小。结论 改良三相图法对寻找低毒性的药用微乳有积极的指导意义。     

药用微乳伪三元相图的几种制备方法比较研究

目的评价目前常用的几种微乳伪三元相图制备方法的优劣。方法选择吐温-80、聚氧乙烯辛基苯基醚(OP)和大豆卵磷脂为乳化剂,乙醇为助乳化剂,肉豆蔻酸异丙酯或油酸乙酯为油相,制备伪三元相图,以相图中数据点的准确性和可靠性等为指标,评价不同方法所得微乳相图的差异。结果不同方法制备的水包油型乳化剂的伪三元相图微乳区面积差异不大,但图中不同区域数据点的准确性和可靠性差异较大;不同方法制备的油包水型乳化剂伪三元相图的各相以及相区的面积差异均较大。结论制备准确可靠的伪三元相图,应根据组分的性质及所制备的微乳类型来选择方法,并综合利用某几种方法来判断滴定终点。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.