多肽蛋白质类药物聚乙二醇化修饰研究进展

综述多肽蛋白质类药物聚乙二醇化修饰的优势、方法、鉴定与检测及局限性等.     

蛋白质、多肽类药物制剂的研究现状

目的：综述蛋白质、多肽类药物制剂的研究现状。方法：依据国内外文献进行综述,包括蛋白质、多肽类药物性能特点、已开发剂型及其制备方法,临床应用效果和发展前景内容。结果：蛋白质、多肽类药物制剂的研究是目前蛋白质、多肽类药物发展的迫切要求,但目前研究工作较少,理论基础研究则更少。结论：蛋白质、多肽类药物将成为21世纪的重要药品,我们应该加强蛋白质、多肽类药物制剂的的研究,使其更适合于临床应用的要求。     

蛋白质多肽类药物非注射制剂研究现状

由于大分子物质具有相对分子质量大、不易透过细胞膜、易在体内酶解、降解代谢途径多样等特点,其临床应用的主要剂型为注射用溶液剂和冻干粉针剂。因而,通过制剂学方法来改变蛋白质多肽类药物的给药形式已成为现代药剂学的研究热点。此文就蛋白质多肽类药物非注射制剂的研究现状进行综述性介绍。     

蛋白质、多肽类药物新型释药系统的研究

现代生物技术的飞速发展,使蛋白质、多肽类药物在临床上的应用越来越广泛。与此同时,蛋白质、多肽类药物递送系统的研究也日益成为现代药剂学的热点之一。本文综述了近年来国内外蛋白质、多肽类药物新型释药系统的发展概况,为蛋白质、多肽类药物制剂的研究和临床应用、开发提供借鉴。     

多肽及蛋白质类药物的研究进展

介绍了目前多肽多蛋白质类药物口服液制的研究概况。     

蛋白多肽类药物聚乙二醇化修饰研究进展

近年来,越来越多具有生物活性的蛋白多肽类药物被发现,因其生理功能上的高效性及专一性而广泛用于治疗各种疾病。但由于其在体内易被降解,且生物半衰期短,使其应用受到了限制。通过化学修饰的方法,可以延长蛋白肽类药物的生物半衰期,提高药效,降低副作用。聚乙二醇能有效增加蛋白多肽类药物在体内的稳定性,本文就聚乙二醇共价连接修饰蛋白质及多肽类药物做一综述。     

蛋白质、多肽类药物新剂型与新技术发展动态

现代生物技术的飞速发展 ,使蛋白质、多肽类药物在临床上的应用日益广泛。与此同时 ,蛋白质、多肽类药物递送系统的研究也成为现代药剂学的一个热点。此文综述了近年来国内外蛋白质、多肽类药物的新剂型和制剂新技术的发展概况 ,希望为蛋白质、多肽类药物制剂的研究和临床应用、开发提供借鉴。     

蛋白质和多肽药物聚乙二醇化的问题与对策

20世纪 70年代Ｄａｖｉｓ等[1] 的开拓性工作 ,使得聚乙二醇化的蛋白质和多肽在生物医学和生物技术等诸多领域得到越来越广泛的应用。蛋白质或多肽药物被适当地聚乙二醇化后 ,其主要的生物学功能保持不变 ,并可获得下述有利性质[2 ,3 ] :(1)溶解度提高 ;(2 )免疫原性降低或消除 ;(3)被水解酶降解的可能性减小 ;(4)被肾脏清除的速率降低 ;(5 )药物体内分布和动力学行为改变 ;(6 )贮存稳定性提高。因此 ,蛋白质和多肽药物的聚乙二醇化一直是药学领域的研究热点。本文就聚乙二醇化过程中所遇到的一些共性问题及其解决办法进行综述。1　聚乙二醇…     

一种新型的蛋白质及多肽胍基的聚乙二醇化试剂的合成

合成了一种新型的蛋白质及多肽胍基的PEG化试剂,其化学本质为mPEG单取代的乙酰丙酮,用于改造蛋白质及多肽的溶解性、稳定性、免疫原性和蛋白质多肽药物的体内循环时间。该方法提供的PEG化试剂主要针对蛋白质及多肽中精氨酸的胍基,具有广阔的应用前景。     

蛋白质和多肽类药物分子化学修饰的研究进展

目的蛋白质、多肽等药物分子免疫原性和毒副反应的存在及体内作用时间短等问题限制了其应用 ,这可以通过化学修饰部分或全部加以克服。随着生物大分子构效关系逐步得到揭示 ,生物大分子化学修饰的研究迅速发展。此文对蛋白质、多肽等药物分子化学修饰的国内外研究现状和发展动态加以评述 ,包括化学修饰原理、化学修饰方法、修饰后药物分子的应用等     

Solvent Exchange Method: A Novel Microencapsulation Technique Using Dual Microdispensers

PURPOSE: A new microencapsulation method called the "solvent exchange method" was developed using a dual microdispenser system. The objective of this research is to demonstrate the new method and understand how the microcapsule size is controlled by different instrumental parameters. METHOD: The solvent exchange method was carried out using a dual microdispenser system consisting of two ink-jet nozzles. Reservoir-type microcapsules were generated by collision of microdrops of an aqueous and a polymer solution and subsequent formation of polymer films at the interface between the two solutions. The prepared microcapsules were characterized by microscopic methods. RESULTS: The ink-jet nozzles produced drops of different sizes with high accuracy according to orifice size of a nozzle, flow rate of the jetted solutions, and forcing frequency of the piezoelectric transducers. In an individual microcapsule, an aqueous core was surrounded by a thin polymer membrane; thus, the size of the collected microcapsules was equivalent to that of single drops. CONCLUSIONS: The solvent exchange method based on a dual microdispenser system produces reservoir-type microcapsules in a homogeneous and predictable manner. Given the unique geometry of the microcapsules and mildness of the encapsulation process, this method is expected to provide a useful alternative to existing techniques in protein microencapsulation.     

药检所仪器设备的质量控制

仪器设备是检测过程中影响数据质量的重要因素之一.因此,必须对仪器设备进行质量控制,使其以良好的技术状态为检验服务,最大限度地发挥投资效益,有效地保证检测数据的准确、可靠.本文以北京市药检所为例,具体介绍了仪器设备的质量控制流程和措施.     

Microencapsulation of mildronate in biodegradable and non-biodegradable polymers

Abstract

The extremely high hygroscopicity (solubility in water ≥2?g/ml) of the pharmaceutical preparation mildronate defines specific requirements to both packaging material and storage conditions. To overcome the above mentioned inconveniences, microencapsulated form of mildronate was developed using polystyrene (PS) and poly (lactic acid) (PLA) as watertight coating materials. Drug/polymer interaction as well as influence of the microencapsulation process variables on microparticle properties was studied in detail. Water-in-oil-in-water double emulsion technique was adapted and applied for the preparation of PS/mildronate microparticles with total drug load up to 77 %wt and PLA/mildronate microparticles with total drug load up to 80 %wt. The repeatability of the microencapsulation process was ±4% and the encapsulation efficiency of the active ingredient reached 60 %wt. The drug release kinetics from the obtained microparticles was evaluated and it was found that drug release in vivo could be successfully sustained if polystyrene matrix has been used.     

Microencapsulation of higher hydrocarbon phase change materials by in situ polymerization

Three higher hydrocarbon phase change materials (PCMs) with melting points of 25, 40 and 50°C were microencapsulated by in situ polymerization of amino-aldehyde resins. Trimethylolmelamine (TMM) and hexamethoxymethylolmelamine (HMMM) were studied as amino-aldehyde pre-polymers for microcapsule wall formation, in combination with emulsifying/modifying agents based on styrene-malein anhydride copolymers (SMA) of different molecular weights and different styrene-maleic acid anhydride ratios. Microcapsule sizes, size distribution and wall permeability were analysed. A mathematical model was developed for comparing the mechanical resistance of different batches of microcapsules, produced at different TMM-SMA ratios. Larger microcapsules with thicker walls and larger pores (M_LAR) expressed lower resistance to breakage than slightly smaller microcapsules with thinner walls and finer pore structure (M_SMA). Mathematical data were confirmed by a smudging colouration test. Laboratory microencapsulation process parameters were optimized to obtain impermeable microcapsules with improved mechanical stability. The process was transferred into a 10?l pilot reactor for two PCMs with melting points of 25 and 40°C. Dry powder of microencapsulated PCMs was obtained by spray drying of aqueous microcapsule suspensions.     

Microencapsulation of Solid Dispersions: Release of Griseofulvin from Griseofulvin:Phospholipid Coprecipitates in Microspheres

The preparation, characteristics, and behavior of microspheres of poly(L-lactic acid) (PLA) containing griseofulvin (Gris) or Gris:phospholipid coprecipitates are described. Microspheres were spherical and increased in size from 17 µm (empty) to 30 µm, containing 22% Gris. The release of coprecipitated Gris after 60 min from 146,000 MW PLA microspheres in pH 2.0 buffer at 37°C was twofold greater than that from microspheres containing pure Gris. Also, the release profile from pure Gris microspheres was 25% lower than its dissolution profile, whereas the dissolution and mi-crosphere release profiles of Gris coprecipitate were the same. Microspheres of Gris coprecipitate suspended in PEG 600 in hard gelatin capsules for 1 week released Gris at levels comparable to the dissolution of coprecipitate. Decreasing the MW of PLA substantially increased the release of Gris from microspheres of coprecipitate after 20 min but insignificantly from microspheres of pure Gris. These findings suggest that microsphere formulation offers some new opportunities in the development of solid dispersions which normally encounter processing difficulties.     

Microencapsulation of Clostridium acetobutylicum ATCC 824 spores in gellan gum microspheres for the production of biobutanol

Abstract

The purpose of the present study was to provide further insights on the applicability of microencapsulation using emulsification method, to immobilise Clostridium acetobutylicum ATCC 824 spores, for biobutanol production. The encapsulated spores were revived using heat shock treatment and the fermentation efficiency of the resultant encapsulated cells was compared with that of the free (non-encapsulated) cells. The microspheres were easily recovered from the fermentation medium by filtration and reused up to five cycles of fermentation. In contrast, the free (non-encapsulated) cells could be reused for two cycles only. The microspheres remained intact throughout repeated use. Although significant cell leakage was observed during the course of fermentation, the microspheres could be reused with relatively high butanol yield, demonstrating their role as microbial cell nurseries. Both encapsulated and liberated cells contributed to butanol production.     

Microencapsulation of Lactobacillus plantarum (mtcc 5422) by spray-freeze-drying method and evaluation of survival in simulated gastrointestinal conditions

Spray-drying (SD) and freeze-drying (FD) are widely used methods for microencapsulation of heat-sensitive materials like probiotics for long-term preservation and transport. Spray-freeze-drying (SFD) is relatively a new technique that involves spraying a solution into a cold medium and removal of solvent (water) by conventional vacuum FD method. In this study, the SFD microencapsulated Lactobacillus plantarum powder (1:1 and 1:1.5 core-to-wall ratios of whey protein) is compared with the microencapsulated powders produced by FD and SD methods. The SFD and FD processed microencapsulated powder show 20% higher cell viability than the SD samples. In simulated gastrointestinal conditions, the SFD and FD cells show up to 4?h better tolerance than SD samples and unencapsulated cells in acidic and pepsin condition. The morphology of SFD samples shows particles almost in spherical shape with numerous fine pores, which in turn results in good rehydration behaviour of the powdered product.     

Microencapsulation in genipin cross-linked gelatine-maltodextrin improves survival of Bifidobacterium adolescentis during exposure to in vitro gastrointestinal conditions

To improve survival during exposure to adverse conditions, probiotic Bifidobacterium adolescentis 15703T cells were encapsulated in novel mono-core and multi-core phase-separated gelatine-maltodextrin (GMD) microspheres where the gelatine (G) phase was cross-linked with genipin (GP). Microscopy showed that encapsulated cells were exclusively associated with maltodextrin (MD) core(s). Small (average diameter 37 µm) and large (70 µm) GMD and G microspheres were produced by modulating factors (e.g. mixing speed, surfactant, GP and G concentrations) affecting the size, structural stability and phase-separation. In vitro sequential gastro-intestinal (GI) juice challenge experiments revealed increased survival of cells encapsulated in GMD (～10^6–7 cfu mL^?1) and G (～10⁵ cfu mL^?1) microspheres as compared to free cells (～10⁴ cfu mL^?1). In GMD microspheres, the bacteria derive energy from MD to survive during exposure to acid and bile salts. In conclusion, the novel food grade GMD microencapsulation formulation was shown to protect probiotic bifidobacteria from adverse conditions.     

微囊化法制备润肠片及其药效学实验研究

目的研究润肠片的制备工艺及其润肠通便功效。方法用微囊化法制备润肠片,考察制剂的形态、片重差异、崩解时限。用肠水分实验、小肠推进实验、排便实验研究了润肠片对在体小鼠肠功能的影响,探讨了润肠片的药理作用。结果所制制剂为淡黄色片剂,检查符合2010年版中国药典中相关规定。润肠片4g.kg-1能极显著增加小鼠肠水分、小肠推进率和排便数(P<0.01),并且作用强于润肠丸(P<0.05)。润肠片2g.kg-1能极显著增加小鼠肠水分与小肠推进率(P<0.01),显著增加小鼠排便数(P<0.05),并且增加肠水分与小肠推进率的作用强于润肠丸(P<0.05)。结论润肠片具有较润肠丸更显著的润肠通便功效,说明本文设计的润肠片的制备工艺合理、有效。     

国外医疗器械研究开发新趋向

近１０年来，世界上发达国家医疗器械工业发展迅猛，新技术、新产品不断涌现。本文就近１０年来，国外发达国家医疗器械研究开发的总趋势作了介绍，并对主要品种今后的发展趋向作了科学的分析预测。