冰片鸦胆子油纳米乳的制备及对大鼠脑胶质瘤的抑瘤作用研究

目的 筛选和优化冰片鸦胆子油纳米乳处方,制备冰片鸦胆子油纳米乳,并初步考察其对大鼠脑胶质瘤的抑瘤作用。 方法 通过柱前衍生化处理,建立GC测定鸦胆子油中油酸含量的分析方法;采用转相法制备冰片鸦胆子油纳米乳;绘制伪三元相图,筛选最佳处方;透射电子显微镜观察外观形态、激光粒度仪测定粒径分布和Zeta电位;构建大鼠脑胶质瘤模型,以瘤重和瘤体积变化为指标,初步考察冰片鸦胆子油纳米乳对大鼠脑胶肿瘤的抑瘤作用。 结果 建立了GC测定鸦胆子油中油酸含量的分析方法,筛选冰片鸦胆子油纳米乳最佳处方为油相肉豆蔻酸异丙酯35%,鸦胆子油(含1%冰片)35%,乳化剂Cremopher RH40 18%,Labrasol 12%,纳米乳外观呈圆整球形,平均粒径(47.60±0.57)nm,PDI为(0.22±0.01),Zeta电位为(-1.06±0.12)mV,载药量(0.424 1±0.005 6)mg·mL^-1。抑瘤实验显示,模型组、鸦胆子油注射剂组、鸦胆子油纳米乳组和冰片鸦胆子油纳米乳组的瘤重分别为(1.32±0.19),(0.84±0.08),(0.76±0.06)和(0.57±0.10)g,肿瘤体积分别为(72.2±9.4),(44.2±5.1),(42.3±4.9)和(27.9±2.5)mm³,鸦胆子油注射剂组、鸦胆子油纳米乳组和冰片鸦胆子油纳米组的肿瘤抑制率分别为36.49%,42.80%和56.94%。 结论 所筛选的最佳处方采用转相法制备冰片鸦胆子油纳米乳,粒径分布均匀,油酸含量较高,稳定性较好。同时冰片鸦胆子油纳米乳对大鼠胶质瘤相对具有较强的抑瘤作用,初步推断冰片可能促进鸦胆子油跨过血脑屏障来提高抑瘤作用。     

猫爪草纳米乳喷喉剂的制备及质量评价

目的研究猫爪草纳米乳喷喉剂的处方与制备工艺,并对其质量进行评价。方法通过绘制纳米乳的伪三元相图筛选制备猫爪草纳米乳喷喉剂所需的油相、乳化剂及助乳化剂,确定最佳处方,并考察其外观、形态、粒径及稳定性。结果根据载药量和空白乳的伪三元相图实验结果最终确定猫爪草纳米乳的最优处方为蓖麻油聚氧乙烯醚(EL-40)-丙三醇-肉豆蔻酸异丙酯(IPM)-水(21.72∶7.24∶10.01∶61.02)。所制得的猫爪草纳米乳喷喉剂为澄清的透明液体,离心后稳定不分层,平均粒径为84±3.12 nm,载药量为20 mg·mL^-1。结论猫爪草纳米乳喷喉剂制备工艺经验证稳定、简便、易行、预测性好,可为猫爪草纳米乳喷喉剂的进一步研发奠定基础。     

芹菜素纳米乳液的制备及其在人工胃肠液中的稳定性研究

目的：本研究以茶皂素为天然乳化剂制备芹菜素纳米乳液(AP-NE),并对其进行人工胃肠液中稳定性与降解动力学特性的考察。方法：采用高速剪切结合高压均质法制备AP-NE,以平均粒径、多分散指数(PDI)和外观为主要评价指标筛选出最优处方与工艺,对其进行理化性质表征,并通过高效液相色谱法,测定AP-NE中药物在不同介质中不同时刻的峰面积,对其在胃肠液中的稳定性进行模拟研究。结果：结果表明AP-NE的最优制备处方为芹菜素质量浓度0.40 wt%、茶皂素质量浓度2.0 mg·mL^-1、油相用量(蓖麻油：辛癸酸甘油酯为1:3)3 mL,最佳工艺参数为剪切速率19000 r·min^-1、剪切时间2 min、均质压力100·103 KPa、均质次数6次;制得的AP-NE平均粒径为(259.5±3.6) nm,PDI为0.103±0.005,Zeta电位为(-35.81±0.38) m V (n=3),溶解度为(128.12±1.35) μg·m L^-1;透射电镜观察乳滴呈大小均一的圆球状;人工胃肠液中的稳定性试验表明,纳米乳中芹...     

效应面法优化吲哚美辛纳米乳的制备工艺及其透皮性能研究

目的优化吲哚美辛(IND)纳米乳的处方工艺,并进行体外透皮性能研究。方法采用伪三元相图和星点效应面法优选IND纳米乳处方,通过改良的Franz扩散池法,考察体外渗透活性。结果 IND纳米乳最优处方:乳化剂和助乳化剂质量比为3∶1,油相比例为34.36%,聚乙二醇400比例为6.36%,平均粒径与包封率的预测结果为54.49 nm和93.57%,实测结果为56.19 nm和91.81%;IND纳米乳与普通乳的稳态渗透速率常数分别为1.318 4和0.738 1 mg·cm^-2·h^-1。结论所优化的处方工艺稳定,模型预测功能良好,制备的IND纳米乳渗透性能显著优于普通乳。     

苦杏仁苷自微乳的制备及理化性质的研究

目的 制备苦杏仁苷自微乳,并进行初步质量评价研究。方法 通过平衡溶解度的测定和伪三元相图的绘制筛选苦杏仁苷的最佳处方,并对苦杏仁苷自微乳的粒径、多分散系数、稳定性进行评价。结果 苦杏仁苷自微乳的最优处方为Peceol/MCT (1︰ 1)-乳化剂OP-1,2-丙二醇=45%︰ 40%︰ 15%,载药量为6 mg·mL^-1。所得苦杏仁苷自微乳平均粒径为(113.3±0.8) nm,多分散系数为(0.171±0.007),离心稳定性良好。结论 优选处方稳定可行,制备的苦杏仁苷自微乳粒径均匀,稳定性良好。     

基于“药辅合一”的紫杉醇-薏苡仁油微乳的制备及含量测定

目的 采用以薏苡仁油替代微乳的油相制备紫杉醇-薏苡仁油微乳,筛选紫杉醇-薏苡仁油微乳制备的最佳处方,并进行紫杉醇含量测定的方法学考察。方法 选用不同的乳化剂和助乳化剂,采用水滴定法绘制出伪三元相图,筛选出最佳乳化剂和助乳化剂,通过观察成乳状态,并以包封率和载药量为指标,筛选出最佳处方制备得到紫杉醇-薏苡仁油微乳,并测定其zeta电位以及粒度分布。结果 紫杉醇-薏苡仁油微乳处方为紫杉醇10 mg,HS 15 600 mg,PEG400 200 mg,薏苡仁油200 mg,包封率为(98.9±1.26)%,载药量为(0.56±0.05)%,紫杉醇-薏苡仁油微乳粒径为(35.23±1.20) nm,zeta电位为(–2.93±0.69)mV。结论 本研究成功制备得到了紫杉醇-薏苡仁油微乳,所得微乳外观完整均一,粒径较小,包封率高,具有一定的药物缓释功能。     

白藜芦醇纳米乳制备与体外质量评价

目的 制备白藜芦醇纳米乳并对其质量进行评价,为其深入研究奠定基础.方法 根据白藜芦醇在油相、乳化剂、助乳化剂中溶解度的测定结果,结合伪三元相图筛选出白藜芦醇纳米乳的最佳处方,并对其外观、粒径、稳定性等进行体外质量评价.结果 白藜芦醇纳米乳的最佳处方为:白藜芦醇:8.47％、聚氧乙烯氢化蓖麻油-40:16.24％、司盘-...     

特比萘芬乳凝胶的制备及质量评价

目的:制备特比萘芬乳凝胶并对其质量进行评价。方法:以溶解度为指标筛选乳化剂和油相,以不同微乳体系的三元相图筛选油相、乳化剂和助乳化剂的用量,采用直接溶胀法制备乳凝胶,并对其含量、体外经皮渗透性、皮肤刺激性、稳定性进行考察。结果:乳凝胶的最优处方(100 g)为丙二醇辛酸酯14.0 g、聚氧乙烯-35-蓖麻油40.0 g、丙二醇2.0 g。制备的特比萘芬乳凝胶含量合格,12 h的体外累积渗透量为(1 283.7±33.5)μg/cm2,皮肤刺激反应评分24 h为0.1、48 h为0(无刺激),稳定性各项指标无明显变化。结论:该制剂制备处方合理,质量可控。     

复方紫草阴道用微乳-原位凝胶的制备与评价

目的 制备复方紫草阴道用微乳-原位凝胶并进行质量评价。方法 以肉豆蔻异丙酯(IPM)为油相,分别以聚氧乙烯-35-蓖麻油(EL-35)和丙三醇为乳化剂和助乳化剂,以泊洛沙姆407(P407)和泊洛沙姆188(P188)为温敏凝胶基质,制备复方紫草微乳-原位凝胶,并对微乳及凝胶的性状、粒径、流变学性质、体外释放特性等进行考察。结果 最佳微乳-原位凝胶处方中凝胶基质组成为P407 100 mg·mL^-1,P188 20 mg·mL^-1,凝胶平均粒径(23.23±0.29)nm。体外释放实验表明,复方紫草微乳-原位凝胶释放符合零级动力学特性,药物释放由凝胶溶蚀决定。结论 复方紫草阴道用微乳-原位凝胶制备工艺简单可行,凝胶具有良好的理化性质及体外释放性能。     

来那度胺纳米水凝胶的制备及其体外透皮吸收研究

目的:制备性质稳定、质量可控的来那度胺纳米水凝胶,评价其理化性质并考察其体外透皮吸收情况。方法:通过对药物溶解度的增加程度初步筛选用于制备来那度胺纳米乳的油相、表面活性剂和助表面活性剂;通过表面活性剂对油相的乳化效果进一步筛选油相;绘制伪三元相图,优化表面活性剂与助表面活性剂的质量比(K_m)。用激光粒度测定仪测定来那度胺纳米乳的粒径。将来那度胺纳米乳分散于卡波姆940中制备来那度胺纳米水凝胶,考察来那度胺纳米乳的外观、形态、pH值、Zeta电位、稳定性以及体外透皮性能。结果:来那度胺纳米乳的最优处方为辛癸酸甘油酯/RH40/1,2-丙二醇/水=1∶4.5∶4.5∶6.95(m/m)。以此处方制备的来那度胺纳米乳澄清透明,外观透亮,pH值为5.20±0.14,平均粒径为(24.76±0.82)nm,多分散指数为0.256±0.088,粒径分布均一,Zeta电位为-47.33 mV,高速离心后无分层现象,耐寒耐热试验前后无明显差异,稳定性良好。来那度胺水凝胶的累积透过量显著高于原料药,透皮性能良好。结论:该研究制备的来那度胺纳米水凝胶处方组成合理、性质稳定、透皮性能良...     

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.

     

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.     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.