壳聚糖包覆的人参皂苷Rg3脂质体的制备及质量评价

目的制备壳聚糖包覆的人参皂苷Rg3脂质体,并进行质量评价。方法采用薄膜分散法、逆相蒸发法、注入法制备脂质体,用壳聚糖包覆;以形态、粒径、包封率为指标筛选制备方法。结果薄膜分散法制备的脂质体外形规则、光滑、平均粒径为10.4μm,包封率为46.96%;壳聚糖包覆后外形圆整,平均粒径为11.1μm,包封率为54.79%。结论采用薄膜分散法制备脂质体并用壳聚糖包覆,质量合格。     

紫杉醇纳米脂质体凝胶剂的制备及体外透皮研究

目的制备紫杉醇纳米脂质体凝胶剂,考察其粒径、粒径分布、包封率、体外释放度及透皮特性。方法采用薄膜蒸发高压微射流法制备紫杉醇纳米脂质体,以卡波姆为凝胶基质,研制紫杉醇纳米脂质体凝胶剂,采用正交试验探索最佳工艺。用粒径测定仪测定脂质体的粒径及其粒径分布,低速-超速相结合法测定包封率,透析膜扩散法进行体外释放试验,以离体小鼠皮结合改良Franz扩散装置考察其体外透皮特性。结果紫杉醇纳米脂质体的最佳工艺:卵磷脂的含量为2%,药物与磷脂质量比为1∶30,磷脂与胆固醇的质量比为10∶1。测得的粒径为81.8 nm;粒径分布系数为0.180;平均包封率73.2%。纳米脂质体凝胶剂72 h累积释放百分率为79.04%;48 h的单位面积累积渗透量为429.68μg·cm?2。结论该制剂制备工艺简单,易于涂布,具有较高的包封率,粒径较小且分布均匀,体外释放缓慢。纳米脂质体能促进脂溶性药物紫杉醇透过皮肤。     

卡巴他赛白蛋白纳米粒的制备及其体外生物相容性评价

目的 制备卡巴他赛白蛋白纳米粒（CBZ-BSA-Gd-NP）以降低药物毒性,并评价其体外生物相容性。方法 采用生物矿化法制备CBZ-BSA-Gd-NP,对其处方工艺进行优化,对粒径、Zeta电位、载药量等性质进行表征,并采用体外溶血试验考察其体外血液相容性。结果 制得的纳米粒包封率为63.04%,载药量为10.51%,平均粒径为（166.1±4.7） nm,粒径的多分散系数（PDI）为0.256,Zeta电位为（-18.14±1.16） mV,与卡巴他赛-吐温溶液相比,体外溶血作用显著降低。结论 该方法操作简便,制备的CBZ-BSA-Gd-NP载药量高,粒径均匀,体外血液相容性好,增加了药物使用的安全性。     

氟比洛芬脂质体的制备及其理化特性

目的:制备氟比洛芬乙醇脂质体并对其理化特性进行评价。方法:采用注入法工艺制备氟比洛芬乙醇脂质体,正交设计法筛 选处方;用粒度分析仪测定粒径大小与分布;用HPLC法测定乙醇脂质体中氟比洛芬的含量及其包封率。结果:制备的脂质体粒径分 布集中,平均粒径为153nm,最大粒径1.3μm,300nm以下占78.1%;包封率为36.28%,25℃条件下贮存3个月,粒径分布无显著变 化,渗漏率小于5%,表明本品稳定性良好。结论:注入法制备乙醇脂质体简便可行,质量控制方法简便、快速、准确、重现性好。     

双氯芬酸钠脂质体的制备及包封率测定

目的:制备双氯芬酸钠脂质体并测定其包封率。方法:以pH梯度法制备脂质体,透射电子显微镜考察其形态与粒径;采用高效液相色谱法测定双氯芬酸钠的包封率。结果:制备的脂质体粒径大小均匀,粒径范围为150～175nm;双氯芬酸钠检测浓度的线性范围为0.01～1mg·mL-1(r=0.9990,n=6),平均回收率为100.05%(RSD=1.21%,n=6);包封率最高可达85.8%,最低52.4%。结论:本方法可制备得到包封率较高的双氯芬酸钠脂质体。     

布洛芬传递体的制备及性质的研究

采用正交设计优化布洛芬传递体处方,制得的布洛芬传递体粒径分布为(122.3±31.9)nm,并以水-甲醇(20∶80,0.1%三氟乙酸)为流动相,HPLC测其平均包封率为48.92%。初步稳定性考察表明,在低温(4℃)贮存7d,制品平均粒径及分布变化小,药物泄漏少于3%,性质较稳定,为布洛芬新的给药技术提供了依据。     

一种稀释法制备脂质体的方法考察

介绍了一种简单的直接稀释制备脂质体的方法,并考察了工艺因素对空白脂质体平均粒径的影响.结果表明,磷脂在乙醇及水化介质中的浓度越低,得到的脂质体粒径越小;水化介质的离子强度越大,得到的脂质体粒径越大.采用本法以多西他赛为模型药物试制得到的脂质体平均粒径为(110±10)nm,包封率为(99.2±1.4)%.     

光敏性多西他赛脂质体的制备、处方优化和体外释放度研究

目的：以富勒烯丙二酸衍生物（DMA-C60）-多西他赛为模型药物,构建光敏性脂质体,增强抗肿瘤效果。系统研究脂质体（LP）的制备工艺、理化性质、处方优化和体外释放特性。方法：采用Bingle环加成反应和酯水解反应合成了DMA-C60,采用傅立叶变换红外光谱（FT-IR）对产物表征定性;采用薄膜法制备DMA-C60-DTX脂质体;超滤离心法测量DTX包封率和载药量;采用激光纳米粒度测定仪测定粒径、粒径分布和Zeta电位;透射电镜测定脂质体外观形态;利用差示扫描量热法（DSC）考察LP中原料药DTX及脂质材料的晶形存在状态;采用透析袋法测量体外释放度并拟合释放模型。结果：采用FT-IR表征定性DMA-C60合成成功。最优处方得到的DMA-C60-DTX-LP,平均粒径约为170 nm,Zeta电位约为-30 mV,DTX包封率（85.76±2.60）%,DMA-C60包封率约为89%;透射电镜观察DMA-C60-DTX-LP呈类球形,粒径大小约为170 nm,分布均匀且与所测粒径大小相符;DSC显示DTX原料药几乎以无定型的状态存在于脂质内核中;DMA-C60的加入并不影响DTX的释放,60 h内累计释放百分数为80%,DTX在LP中体外释放行为可用Ritger-Peppas释放动力学方程进行描述。结论：光敏性多西他赛脂质体载药量和包封率较高、脂质体外观呈类球形,粒径较小且分布均匀,体外释放具有一定的缓释作用。     

冬凌草甲素纳米粒制备及其体外抗肿瘤作用

目的制备冬凌草甲素纳米粒(ORI-Nps),考察其体外抗肿瘤作用.方法采用界面沉淀法制备ORFNps,并对其形态、粒径、ξ电位、包封率、载药量、体外释药特征和抗肿瘤作用进行研究.结果制备的ORI-Nps为类球形,粒径分布均匀,平均粒径为101.5 nm;ξ电位为-29.8 mV;载药量和包封率分别为6.84%和92.25%;体外释药缓慢;对Eta-109细胞具有较强的毒性作用.结论制备的ORI-Nps包封率和载药量高,粒径均匀,体外释药具有缓释特点,体外抗肿瘤作用强.     

兰索拉唑脂质体的制备及性质考察

目的研究兰索拉唑阳离子脂质体的制备方法并考察其体外释放行为及稳定性等。方法采用正交设计筛选处方;采用乙醇注入法制备兰索拉唑脂质体;采用超滤法测定其包封率;采用透射电镜观察脂质体的外观形态;采用粒径分析仪和Zeta电位仪分别测定脂质体的粒径和Zeta电位;采用透析法考察脂质体的释放规律。结果制得的脂质体包封率约为(80±1.23)%(n=3);脂质体的形态为粒径均匀的球形和类球形;粒径为(184±21)nm(n=3),Zeta电位为(36.1±5)mV(n=3);脂质体的体外释放符合一级方程,具有较好的稳定性。结论优选得到的脂质体处方和制备工艺合理,制剂性质稳定,其体外释放具有缓释特点。     

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.     

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.