奥沙普秦壳聚糖-海藻酸钠缓释微球的制备

目的：目的：选择奥沙普秦作为模型药制备壳聚糖-海藻酸钠缓释微球。方法：采用滴制法制备奥沙普秦壳聚糖-海藻酸钠缓释微球，通过正交试验设计优化了处方和工艺，考察其理化特征及体外释药行为。结果：优化处方制得的微球包封率及载药量分别为98．36％和16．26％，平均粒径为（346．6±164．1）μm；1h药物释放达到36％，随后药物的释药行为是一个缓释过程。结论：制得了载药量较大，包封率较高的奥沙普秦壳聚糖-海藻酸钠缓释微球。     

阿奇霉素羧甲基壳聚糖微球的处方优化及质量评价

目的 优化阿奇霉素羧甲基壳聚糖微球的处方工艺，对其进行表征和质量评价。方法 采用乳化交联法制备阿奇霉素羧甲基壳聚糖微球；在单因素试验的基础上，采用星点设计-效应面法优化其处方工艺；采用红外光谱分析法(fourier transform infrared spectrum, FTIR)、X-射线衍射法(X-ray diffraction, XRD)和扫描电镜对其结构形态进行分析；采用透析法考察其体外释放行为；通过测定微球在模拟唾液中的释放度评价其掩味能力。结果 最优处方工艺为油水体积比4.5,载体质量浓度为36 g·L^-1,固化时间为2.8 h,制得的微球包封率为(86.32±1.52)%,载药量为(12.08±0.14)%;微球表面光滑圆整，分布均匀；FTIR和XRD结果均证实阿奇霉素被包裹于羧甲基壳聚糖中；微球在pH 6.8磷酸盐缓冲液中8 h稳定释放；在模拟唾液中30 s的释放浓度低于其苦味阈值。结论 此制备工艺可行，制得的微球载药量和包封率较高，释药稳定，口感适宜。     

鞣花酸壳聚糖-海藻酸钠微球的制备工艺

目的:优化鞣花酸壳聚糖-海藻酸钠微球的最佳制备工艺。方法:采用一步法,以壳聚糖-海藻酸钠作为载体材料制备鞣花酸微球,并以微球载药量和包封率为考察指标,通过单因素筛选及正交设计优化出鞣花酸壳聚糖-海藻酸钠微球的制备工艺。用溶出仪在900 ml释放介质(pH 6.86)和120 r·min^-1转速条件下测定释放度。结果:优化工艺为海藻酸钠与药物比为3:1,氯化钙质量分数为2%,海藻酸钠质量分数为2%,壳聚糖质量分数为0.1%,温度为60℃,pH为5,所得鞣花酸平均粒径为(980±100)μm,平均载药量为27.22%,平均包封率为97.73%,48 h释放度为74.22%。结论:本制备工艺稳定,操作简便,重现性好,可用于鞣花酸壳聚糖-海藻酸钠微球的制备。     

牛血清白蛋白阳离子微球的制备及体外评价

目的制备牛血清白蛋白（BSA）口服阳离子微球,考察天然阳离子物质壳聚糖（CHS）的加入对蛋白微球的粒径、电动电势、包封率、载药量及体外释放情况的影响。方法以乳酸／羟基乙酸共聚物（PLGA）和壳聚糖（CHS）为载体材料,采用W／O／W复乳-溶剂挥发法制备牛血清白蛋白乳酸／羟基乙酸共聚物-壳聚糖（PLGA／CHS）阳离子微球。通过正交设计优化制备工艺,确定最佳处方。建立准确而简便的蛋白含量测定方法,并对微球进行体外评价。结果最佳处方为：BSA浓度为150g·L^-1、PLGA浓度为8％、外水相体积为80mL、壳聚糖浓度为0．2％。制得的微球形态圆整,平均粒径为（6．9±5．5）μm,为表面荷正电的阳离子微球[ζ电势=00．0±0．6）mV],包封率为（75．4±4．6）％,载药量为（9．3±0．2）％。体外释放结果表明,在模拟胃液和模拟肠液中,壳聚糖的加入均能减少突释,延缓药物的释放。结论与PLGA微球相比,制得的PLGA／CHS阳离子微球表面带正电,具有较高的包封率和载药量,可以延缓药物释放,同时减少突释现象。     

壳聚糖-海藻酸钠幽门螺杆菌全菌蛋白微球的制备及表征

目的以壳聚糖、海藻酸钠为主要材料包裹幽门螺杆菌(HP)全菌超声蛋白抗原,制备新型HP疫苗制剂。方法将海藻酸钠、壳聚糖、大豆油以及HP超声全菌抗原制备成W/O/W型微球。通过扫描电镜、粒径分布仪等检测微球粒径大小;药物溶出度仪、BCA蛋白试剂盒检测微球的蛋白包封率及药物释放速率。结果所制备的微球形态规则,平均粒径3.33μm;蛋白包封率约为64.8%;微球呈显著缓释模式,缓释时间可达6d。结论壳聚糖-海藻酸钠微球包裹全菌蛋白可以作为HP疫苗的新型缓释制剂。     

胰岛素肠溶微球口服的实验研究

目的 :研制一种可供口服的胰岛素肠溶微球。方法 :采用相分离法制备胰岛素丙烯酸树脂微球 ;建立放射性免疫法测定微球包封率 ;利用体外实验法考察微球的抗酸及肠溶能力 ;将不同处方的微球给大鼠灌胃 ,测定其血糖变化。结果 :制得微球粒径分布在 2～ 7μm ;包封率 95 .17% ;在人工胃液中 2h有少于 14%的胰岛素释放 ;在人工肠液中 1h内胰岛素的释放度达 96 % ;微球可使大鼠产生明显的降血糖效果。结论 :胰岛素口服肠溶微球是一类具有发展前景的制剂。     

乳化-溶剂扩散法制备克拉霉素缓释微球

目的探讨克拉霉素缓释微球的制备工艺。方法以Eudragit RS／RL为囊材,采用乳化一溶剂扩散法制备克拉霉素缓释微球,考察对微球质量、收率、载药量和包封率有影响的处方因素。结果EudragitRS／RL与药物按4：1混合时可得到成形性较好、表面光滑、均匀圆整、分散性好的克拉霉素微球。克拉霉素微球的粒径范围为88～180μm,微球的收率为76．0％,载药量为17．8％,包封收率为67．0％。在pH=5．0的磷酸缓冲液中微球中的克拉霉素缓慢释放。结论乳化-溶剂扩散法适合于克拉霉素缓释微球制备。     

紫杉醇壳聚糖肺靶向微球的制备

目的研制具有肺靶向性的紫杉醇壳聚糖微球,并对处方工艺进行优化。方法以壳聚糖为载体,采用乳化一化学交联法制备紫杉醇壳聚糖微球。单因素试验考察了油／水体积比、紫杉醇浓度、乳化时间、乳化剂量等因素,采用正交设计优化微球制备工艺,以HPLC法测定微球载药量、包封率。结果制得的微球显微观察形态圆整、表面光滑,无黏连;平均粒径为（8．23±0．25）μm,粒径在7～12μm平均占微球总数的84．2％,载药量为16．20％±1．15％,包封率为81．29％±1．62％。结论筛选的最佳处方工艺制备的微球粒径大小适宜,可满足肺靶向微球的要求并免除过敏试剂的加入。     

载环孢素A海藻酸钙-壳聚糖微球的制备及体外释放特性

目的:针对角膜移植术后免疫抑制治疗需求,制备眼部局部给药的小粒径载环孢素A缓释微球,并进行体外释放考察。方法:以海藻酸钠、壳聚糖为载体材料,采用静电液滴工艺,通过向制备体系添加表面活性剂,制备小粒径载环孢素A微球,设计正交试验优化处方工艺,扫描电镜观察微球表面形态,动态透析法考察微球的体外释放特性。结果:所制微球形态良好,粒径分布窄,平均粒径为(12.4±0.8)μm,包封率为(82.8±1.8)%,载药量为(50.1±1.2)%,体外释放行为用Higuchi方程拟合效果最好。结论:采用静电液滴工艺,通过减小制备体系的表面张力,制备了球形度优良、粒径小、包封率和载药量较高的载环孢素A的壳聚糖-海藻酸盐缓释微球,所得制剂的体外释药规律服从扩散机制。     

响应面法优化肉苁蓉松果菊苷肠溶微球的制备

目的 制备肉苁蓉松果菊苷肠溶微球,筛选最佳制备工艺,并考察其体外释放特性。方法 用离子凝胶-干燥法制备肉苁蓉松果菊苷肠溶微球,以包封率为考察指标,用响应面法优化其制备工艺。结果 制备肉苁蓉松果菊苷肠溶微球最佳工艺参数：海藻酸钠浓度36.33 mg/ml、氯化钙浓度10.82 mg/ml、壳聚糖浓度10.93 mg/ml。结论 优选的工艺稳定、可行,制备的微球包封率高、缓释效果较好。     

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.     

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.