海藻酸钠及其衍生物在生物医药中的应用进展

目的:总结海藻酸钠及其衍生物在生物医药中的应用进展,为其临床应用与开发提供参考。方法:以"海藻酸钠""衍生物""组织工程""介入治疗""缓释""靶向""载体""Alginate""Derivative""Tissue engineering""Intervention""Control release""Target""Delivery"等为关键词,组合查询1990年1月-2019年4月在中国知网、维普网、ScienceDirect、PubMed等数据库中的相关文献,归纳海藻酸钠衍生物的种类,并从药物递送、创面修复、组织工程、介入治疗等4个方面总结海藻酸钠及其衍生物在生物医药中的应用进展。结果与结论:共检索到相关文献13 387篇,其中有效文献63篇。海藻酸钠衍生物包括基团衍生物(乙酰化衍生物、磷酸化衍生物、硫酸化衍生物)和接枝共聚物。在药物递送方面,海藻酸钠及其衍生物可作为缓控释药物载体、生物大分子载体、靶向给药载体递送药物;在创面修复方面,海藻酸钠及其衍生物可被开发为各类医用敷料,达到止血、抗菌、促进创面愈合等效果;在组织工程方面,海藻酸钠及其衍生物可作为细胞微囊化载体或支架材料,为细胞提供生长支撑的同时还可递送生物活性分子,在软骨、硬骨、皮肤组织修复方面应用广泛;在介入治疗方面,海藻酸钠及其衍生物可将血管栓塞介入治疗和靶向药物治疗相结合,实现药物局部富集,增强疗效。临床上海藻酸钠通常被制成水凝胶进行应用,但存在机械强度差、对疏水性分子负载量低、降解不易控制等缺点,通过乙酰化、磷酸化、硫酸化等形成相应的衍生物可扩大其应用范围,但海藻酸钠及其衍生物的应用仍然存在一些问题,如其力学性能和生物相容性还有待提高、产生的细胞毒性仍需降低,因此,在后续研究中还需深入挖掘海藻酸钠及其衍生物的应用潜能和安全性,为其临床应用提供依据。     

葛根素缓释复合骨架片理化性质的研究

目的利用甲壳胺 海藻酸钠的聚合物作为新型缓控释制剂的复合骨架材料 ,并对其性质及影响因素进行研究。方法利用天然高分子材料甲壳胺 (CS) (阳离子型 )与海藻酸钠 (AL) (阴离子型 )模拟在体内条件下形成聚电解质复合物。通过DTA及IR图谱的峰值变化证明这种复合物确实存在 ,形成的关键是控制好两种电解质的比例。结果当WCS∶WAL=2∶3时 ,反应最完全。利用制成的聚电解质复合物 ,制备葛根素缓释复合骨架片 ,缓释效果符合中国药典规定。结论甲壳胺 海藻酸钠形成的复合物可以做缓、控释制剂的骨架材料。     

羟丙甲纤维素在药物制剂方面的应用与研究

目的介绍羟丙甲纤维素（HPMC）在药物制剂方面的应用及研究进展。方法查阅近年国内文献，根据HPMC的性质和特点，阐述它在片刺、缓释与控释材料、胶囊囊材和混悬型液体制剂等方面的应用。结果HPMC作为黏合剂和崩解剂能显著提高片剂的溶出度或释放度，作为包衣成膜材料可大大提高药物稳定性，作为缓控释骨架材料可阻滞药物释放而达到缓控释药物的目的，作为胶囊囊材在药物的崩解溶出和稳定性方面优于明胶囊材，作为助悬剂使混悬型液体制剂更加稳定。结论HPMC是一种优良的药用辅料，具有广阔的应用前景。     

长春西汀海藻酸钠骨架片体外释药影响因素研究

目的以海藻酸钠为骨架材料 ,制备长春西汀控释骨架片 ,对影响其体外释放的多种因素进行了考察。方法以海藻酸钠为亲水骨架材料 ,粉末直接压片制备长春西汀控释片 ,采用《中华人民共和国药典》2 0 0 0年版二部收载的溶出度测定方法Ⅱ法 (桨法 ) ,测定药物在不同条件下的体外释放度 ,考察海藻酸钠用量及黏度 ,枸橼酸用量 ,释放介质离子强度和pH值对药物体外释放行为的影响。结果与结论海藻酸钠用量及黏度 ,枸橼酸用量 ,释放介质离子强度和pH值均对药物体外释放行为有显著影响。值得注意的是 ,通过调节处方中枸橼酸用量可以使释药行为达零级 ,这为制备长春西汀控释片提供指导 ,有进一步开发的价值。     

药用高分子在缓控释制剂中的应用现状

<正>缓控释制剂的发展除与制药设备的不断发展、革新有关外,药用高分子在该类制剂中也是不可分割的重要组成部分。近年来,一些新型高分子材料的研究和应用使缓控释制剂步入了定时、定向、定位、速效、高效、长效的精密化给药阶段,出现了口服渗透泵控释制剂、脉冲式释药系统、环境敏感型定位释药系统、结肠定位给药系统等新型缓控释制剂。辅料的成分、组成与结构对药物的释放性能有很大的影响,因此在缓控释制剂中合理应用新型高分子材料,就具有重要的意义。1药用高分子作为药物载体药用高分子的广泛研究和应用,促进了缓控释制剂的快     

ZnS-壳聚糖海藻酸钠包裹布洛芬纳米微球的制备和性能研究

目的以壳聚糖-海藻酸钠为基质材料,掺杂入纳米ZnS包裹非甾体抗炎药物布洛芬,制备缓、控释性能优异的载药纳米微球;为研发四代新剂型打下基础。方法利用复凝聚法,通过调整添加基质材料速度、反应温度、搅拌速度等,制备含ZnS的壳聚糖海藻酸钠布洛芬纳米微球,透射电镜观察纳米微球的形态,测试纳米微球的载药量与包封率,拟肠液条件下测试所致纳米微球的释放特性。结果含ZnS壳聚糖海藻酸钠布洛芬纳米载药微球的粒径约为80~100nm,载药量为40.2%药物包封率78.2%,ZnS粒径3nm。在水溶液、0.9%NaCl和磷酸盐缓冲液中的吸水膨胀程度小于不含ZnS的载药纳米微球;体外拟肠条件溶出表明含ZnS的载药纳米微球具有良好的缓控释性能,药代动力学特征为被动扩散。结论掺入了ZnS的壳聚糖海藻酸钠布洛芬纳米微球,形状圆整,包封率理想,具有良好的缓控释性能。     

海藻酸钠在临床的应用

目的：对海藻酸的临床应用的纵深发展之势提起重视。方法：微机检索近几年来海藻酸临床应用的有关文献。结果：海藻酸钠可用于制备控释制剂、用作创作修复材料、治疗返流性食管炎、防治放射性损伤、恢复血容量、降血脂、降血糖、治疗习惯性便秘、增强免疫功能等，对改善水质，净化环境有一定经济价值，海藻酸钠无明显不良反应。结论：海藻酸钠的进一步开发，很有前途。     

天然高分子材料作为药物缓控释载体应用的研究进展

由天然高分子材料构成的药物缓控释载体具有调节药物释放速率、稳定药物成分、提高生物利用率和帮助药物靶向定位等优点。本文简单介绍了胶原蛋白、纤维蛋白、纤维素、壳聚糖、海藻酸及海藻酸盐和魔芋葡甘聚糖作为药物缓控释载体的研究进展。     

海藻酸钠骨架材料中药物释放的影响因素

目的以海藻酸钠为亲水骨架材料，考察药物从海藻酸钠骨架片中释放的体外影响因素。方法以茶碱为模型药物，采用直接压片法制备了茶碱海藻酸钠亲水骨架片，通过对骨架片膨胀性、吸水性以及溶蚀性的考察，研究了影响药物从海藻酸钠骨架材料中释放的体外因素。结果茶碱海藻酸钠骨架片的释药速率和释药机理与骨架片中海藻酸钠粘度、释放介质pH值、离子强度以及转速均有关。结论海藻酸钠能有效地控制骨架片中药物的释放，是一种优良的亲水骨架材料。     

药物控释制剂载体的研究进展

目的药物控释制剂载体是随着药物学、生物材料科学和临床医学的发展而新兴的给药技术。药物控制释放体系在机体内显示出被动靶向、缓释的优点。药物缓释载体材料起着关键作用。笔者重点对几类药物控释载体材料的应用及发展进行综述。方法查阅国内外相关文献并进行分析、归纳。结果了解适合不同药物的药物载体材料,有助于达到理想的药物控制释放效果。结论药物控释制剂具有很广阔的应用前景,目前药物载体的研究还主要是基于材料学的角度,应当加强其药剂学、药动学方面的研究。     

Preparation and release characteristics of polymer-coated and blended alginate microspheres

To prevent a rapid drug release from alginate microspheres in simulated intestinal media, alginate microspheres were coated or blended with polymers. Three polymers were selected and evaluated such as HPMC, Eudragit RS 30D and chitosan, as both coating materials and additive polymers for controlling the drug release. This study focused on the release characteristics of polymer-coated and blended alginate microspheres, varying the type of polymer and its concentration. The alginate microspheres were prepared by dropping the mixture of drug and sodium alginate into CaCl(2) solution using a spray-gun. Polymer-coated microspheres were prepared by adding alginate microspheres into polymer solution with mild stirring. Polymer-blended microspheres were prepared by dropping the mixture of drug, sodium alginate and additive polymer with plasticizer into CaCl(2) solution. In vitro release test was carried out to investigate the release profiles in 500 ml of phosphate buffered saline (PBS, pH 7.4). As the amount of polymer in sodium alginate or coating solution increase, the drug release generally decreased. HPMC-blended microspheres swelled but withstood the disintegration, showing an ideal linear release profiles. Chitosan-coated microspheres showed smooth and round surface and extended the release of drug. In comparison with chitosan-coated microspheres, HPMC-blended alginate microspheres can be easily made and used for controlled drug delivery systems due to convenient process and controlled drug release.     

Evaluation and preparation of controlled release lipid micropheres of sulphamethizole by a congealable disperse phase encapsulation method

A congealable disperse phase encapsulation method was used to prepare controlled release lipid microspheres of sulphamethizole as a model drug. Hydrogenated cotton seed oil (HCSO) and stearic acid were employed as the lipid matrix materials. Tween 60 was the droplet stabilizer used to form microspheres. In in vitro dissolution tests, the drug release was found to be affected by the type of lipid material depending on hydrophilicity. Generally, an initial rapid release followed by a slower release of the drug from the lipid microspheres was observed. Lipid microspheres were also compressed in the tablet form to prevent the initial rapid release of the drug. But the drug release drastically decreased. To achieve a controlled release of the drug. Eudragit L as a channeling agent was added internally to HCSO-microspheres. Although the drug release increased, the controlled release pattern was not achieved. The external addition of polyethyleneglycole 4000 to HCSO-microspheres before compressing tablets, did not produce an affirmative change in the release profile. The lipid microspheres prepared by stearic acid released all of the drug within 1 h. Upon compression, the drug release was very low. Therefore, stearic acid-microspheres were compressed in the tablet form adding disintegrating agents, sodium alginate and Ac-Di-Sol (cross-linked sodium carboxymethylcellulose). A pH-dependent drug release was obtained from the tablets containing sodium alginate. With the tablets of stearic acid-microspheres containing Ac-Di-Sol, the controlled release could be achieved due to gradual disintegration from the tablet to aggregates, and to individual microspheres. Furthermore, in vivo study on 6 healthy volunteers confirmed the controlled release pattern of this dosage form.     

海藻酸钠在盐酸二甲双胍缓释片中的应用

目的：采用海藻酸钠作为缓释材料制备盐酸二甲双胍缓释片。方法通过自制样品与原研药进行体外溶出曲线及稳定性的对比,考察海藻酸钠作为缓释材料在盐酸二甲双胍缓释片中的缓释效果。结果试验处方制得的盐酸二甲双胍缓释片与原研药对比几条关键 pH 溶出介质体外溶出曲线,相似因子（f2）达到70以上;试验处方制得的盐酸二甲双胍缓释片有关物质基本无增加;试验处方制得的盐酸二甲双胍缓释片片重约850 mg,原研药约1000 mg。结论采用海藻酸钠作为缓释材料制备的盐酸二甲双胍缓释片与原研药的体外释放相似度高;处方、工艺稳定可行,质量可控。     

Release characteristics of chitosan treated alginate beads: II. Sustained release of a low molecular drug from chitosan treated alginate beads

The aim of this paper was to investigate the possible applicability of chitosan treated alginate beads as a controlled release system of small molecular drugs with high solubility. Timolol maleate (mw 432.49) was used as a model drug. The beads were prepared by the ionotropic gelation method and the effect of various factors (alginate, chitosan, drug and calcium chloride concentrations, the volume of external and internal phases and drying methods) on bead properties were also investigated. Spherical beads with 0.78-1.16 mm diameter range and 10.8-66.5% encapsulation efficiencies were produced. Higher encapsulation efficiencies and retarded drug release were obtained with chitosan treated alginate beads. Among the different factors investigated such as alginate, drug, chitosan and CaCl2 concentrations, the volumes of the external and internal phases affected bead properties. The drying technique has an importance on the bead properties also. The release data was kinetically evaluated. It appeared that chitosan treated alginate beads may be used for a potential controlled release system of small molecular drugs with high solubility, instead of alginate beads.     

Release characteristics of chitosan treated alginate beads: II. Sustained release of a low molecular drug from chitosan treated alginate beads

The aim of this paper was to investigate the possible applicability of chitosan treated alginate beads as a controlled release system of small molecular drugs with high solubility. Timolol maleate (mw 432.49) was used as a model drug. The beads were prepared by the ionotropic gelation method and the effect of various factors (alginate, chitosan, drug and calcium chloride concentrations, the volume of external and internal phases and drying methods) on bead properties were also investigated. Spherical beads with 0.78-1.16mm diameter range and 10.8-66.5% encapsulation efficiencies were produced. Higher encapsulation efficiencies and retarded drug release were obtained with chitosan treated alginatebeads. Amongthedifferentfactors investigatedsuchas alginate, drug, chitosan and CaCl₂ concentrations, the volumes of the external and internal phases affected bead properties. The drying technique has an importance on the bead properties also. The release data was kinetically evaluated. It appeared that chitosan treated alginate beads may be used for a potential controlled release system of small molecular drugs with high solubility, instead of alginate beads.     

In vitro and in vivo evaluation of anti-inflammatory agents using nanoengineered alginate carriers: towards localized implant inflammation suppression

The aim of this research was to develop nanoengineered alginate microspheres for localized delivery of anti-inflammatory drugs (dexamethasone and diclofenac sodium) for implantable "Smart tattoo" glucose biosensor used for continuous glucose monitoring. The formulation was prepared and characterized for in vitro drug release from uncoated and polyelectrolyte-coated microparticles. Biocompatibility was then tested using L929 cell-line; pilot in vivo studies with Sprague-Dawley (SD) rat subjects were performed to test the suppression of inflammation and fibrosis associated with implantation and was analyzed using standard hematoxylin and eosin staining method. The drug-loaded microspheres were able to deliver the drug for 30 days at a controlled rate with zero-order kinetics. The layer-by-layer self-assembly technique was used to effectively limit the burst release of drug from the matrix. Cell culture studies prove that the material are not cytotoxic and showed acceptable >80% cell viability in all the tested samples. In vivo studies show that both drugs were successful in controlling the implant/tissue interface by suppressing inflammation at the implant site. It was clearly evident that the combined approach of drug loaded carriers along with implanted biosensor shows promise in improving sensor biocompatibility and functionality. Thus, suggesting potential application of alginate microspheres as "smart-tattoo" glucose sensors.     

Release characteristics of chitosan treated alginate beads: I. Sustained release of a macromolecular drug from chitosan treated alginate beads

Alginate and chitosan treated alginate beads were prepared and compared as an oral controlled release system for macromolecular drugs. Dextran (M.W. 70,000) was used as a model substance. The beads were prepared by the ionotropic gelation method and the effect of various factors (alginate, chitosan, drug and calcium chloride concentrations, the volume of external and internal phases and drying methods) on bead properties were investigated. The addition of chitosan increased the drug loading capacity of the beads, and larger beads were obtained in the presence of chitosan. On the other hand, addition of chitosan in the gel structure reduced the drug release from beads. The erosion of the beads was suppressed by chitosan treatment. The drying method was important to the properties of the chitosan-alginate beads. It is proposed that chitosan treated alginate beads may be used as a potential controlled release system of such macromolecules.     

酮洛芬果胶钙凝胶小球和海藻酸钙凝胶小球的制备及性能比较

目的酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球的制备及性能比较。方法利用果胶、海藻酸钠及二者不同比例,以酮洛芬为模型药物采用滴制法制备凝胶小球,考察2种多糖物质对药物包封率和释放行为的影响。利用大鼠肠囊外翻实验对凝胶小球的生物黏附性能进行比较,通过对释放机理的探讨和凝胶小球溶胀性的测定进一步证明2种凝胶小球释药行为的不同。结果酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球均具有良好的生物黏附性能,果胶钙凝胶小球主要通过溶胀作用缓慢释药,而海藻酸钙凝胶小球的释药与凝胶小球慢慢吸水后骨架溶蚀有关。结论酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球通过与生物黏膜的紧密结合缓慢释药,而二者的释放行为有所不同。     

红景天苷缓释微胶囊的制备及体外释放特性研究

目的:制备红景天苷微胶囊,测定其包封率,并考察其体外释药特性。方法:以生物相容性良好的壳聚糖和海藻酸钠为囊壁材料,红景天苷药物微粒为囊芯,采用静电吸引层层纳米自组装技术(LBL法)制备红景天苷微胶囊。结果:制备的微胶囊包封率较高,达到78.02±0.72%;不同包裹层数的微胶囊在体外释放速度不同。结论:用LBL法制备的红景天苷微胶囊具有较高的包封率和缓释特性,具有一定的应用前景。     

Design and evaluation of a dry coated drug delivery system with an impermeable cup, swellable top layer and pulsatile release

In this investigation a novel oral pulsatile drug delivery system based on a core-in-cup dry coated tablet, where the core tablet surrounded on the bottom and circumference wall with inactive material, is proposed. The system consists of three different parts, a core tablet, containing the active ingredient, an impermeable outer shell and a top cover layer-barrier of a soluble polymer. The core contained either diclofenac sodium or ketoprofen as model drugs. The impermeable coating cup consisted of cellulose acetate propionate and the top cover layer of hydrophilic swellable materials, such as polyethylene oxide, sodium alginate or sodium carboxymethyl cellulose. The effect of the core, the polymer characteristics and quantity at the top cover layer, on the lag time and drug release was investigated. The results show that the system release of the drug after a certain lag time generally due to the erosion of the top cover layer. The quantity of the material, its characteristics (viscosity, swelling, gel layer thickness) and the drug solubility was found to modify lag time and drug release. The lag time increased when the quantity of top layer increased, whereas drug release decreased. The use of sodium carboxymethyl cellulose resulted in the greatest swelling, gel thickness and lag time, but the lowest drug release from the system. Polyethylene oxide showed an intermediate behaviour while, the sodium alginate exhibited the smallest swelling, gel thickness and the shortest lag time, but the fastest release. These findings suggest that drug delivery can be controlled by manipulation of these formulations.