参葛滴丸成型工艺研究

目的:确定参葛滴丸的成型工艺条件。方法:以滴丸的丸重差异及外观(圆整度、硬度、色泽)作为评价指标,采用单因素考察法对基质、冷却剂的种类、药液温度进行了选择;采用交叉试验对两种基质的比例及药物与基质的比例进行了优选。结果:优选的最佳成型工艺条件为:以甲基硅油为冷却剂,PEF4000:PEG6000=2:3作为基质,药物与基质比例为1:1.5,滴速为25—30d/min。结论:优选出的成型工艺条件稳定可行。     

HPLC法测定抗宫炎凝胶剂中金石蚕苷含量的研究

目的:采用高效液相色谱法(HPLC)测定抗宫炎凝胶剂中金石蚕苷的含量,为制定其质量标准提供基础。方法:采用十八烷基硅烷键合胶为填充剂,乙腈-0.5%磷酸(18:82)为流动相;检测波长为332 nm;流速为1.0 ml/min,探讨HPLC测定抗宫炎凝胶剂中金石蚕苷含量的专属性、精密度、稳定性、重现性等。结果:金石蚕苷在0.104~0.468 mg/ml范围内呈良好的线性关系(r=0.9999),平均回收率为99.76%,RSD为1.56%。结论:采用HPLC测定抗宫炎凝胶剂中金石蚕苷含量的专属性、精密度、稳定性、重现性均良好,该方法简便可靠,可用于抗宫炎凝胶剂的质量标准的研究。     

复方独一味凝胶贴膏的处方优化和制备工艺研究

以初黏力、赋形性、综合感官为评价指标,采用Box-Behnken设计对基质处方进行优化,以流变性为评价指标筛选载药量,采用延压法涂布制备,考察物料添加顺序、搅拌速度与时间、干燥温度和时间等工艺参数。优选的基质处方为Viscomate~(TM) NP-700 5.0 g、甘羟铝0.14 g、甘油25 g、EDTA 0.2 g,载药量84 g浸膏。制备的复方独一味凝胶贴膏的外观光滑平整,具有适宜的黏附性,无膜残留,皮肤追随性较好,制备工艺简单、稳定、可行。     

双载体制备青蒿素速释型固体分散体工艺优化研究

对载体类型影响青蒿素固体分散体中药物溶出度进行研究及优化制备工艺。以大豆卵磷脂与PEG 6000或聚乙烯吡咯烷酮为双分散载体,采用溶剂法制备青蒿素速释型固体分散体,以溶出度为考察指标,单因素试验筛选载体类型及最佳制备工艺;并采用红外吸收光谱法(IR)、差示扫描量热法(DSC)进行物相表征,明确载体-药物存在状态。结果表明在50 min内卵磷脂-PVP K30双载体比卵磷脂-PEG 6000药物溶出度更高,制备固体分散体为速释型,50 min内总溶出度87%以上,显著高于原料药和物理混合物,且优化最佳工艺条件为卵磷脂与PVP K30比为1∶7,搅拌时间30 min,无水乙醇用量20 mL。IR及DSC结果显示在固体分散体中药物可能以无定型状态存在。双载体制备青蒿素速释型固体分散体工艺简单可行,可显著提高药物溶出度,为提高青蒿素疗效奠定重要基础。     

川归痹消巴布剂基质配方研究

目的:优选川归痹消巴布剂最佳基质配方。方法:以感官评价(膜残留、均匀性、涂展性)、初黏力、内聚力为评价指标,采用正交试验法,研究筛选基质配方中不同组分的用量,优选最佳配比。结果:优选川归痹消巴布剂最佳基质处方配比为:聚丙烯酸钠:甘油:氢氧化铝:枸橼酸:羧甲基纤维素纳=2:12.5:2:0.5:10(重量比)。结论:优选所得的基质均匀性、涂展性好,无残留,黏附性较好,制备工艺合理。     

姜黄素壳聚糖微球的制备及其在体内外释放度的研究

目的:研究响应面法优化姜黄素壳聚糖微球制备的工艺参数,提高姜黄素的溶出度.方法:采用离子交联法制备姜黄素缓释微球,以微球的载药量和包封率为考察指标,采用星点设计考察配制壳聚糖的醋酸浓度、药物载体的比例以及交联剂浓度对微球制备工艺的影响,对结果进行二次多项式拟合,并根据最佳数学模型进行预测.结果:姜黄素壳聚糖微球最优制备工艺参数为:醋酸的浓度为1％,载体药物比例为0.83,交联剂的浓度为0.15％,载药量和包封率的预测值和理论值偏差分别为0.47％和3.2％.结论:响应面法优化姜黄素壳聚糖微球制剂处方具有很好的预测性,体内外药物释放度研究表明,最优条件下制备的微球可以在提高姜黄素溶出度的前提下缓慢释放达12h.     

椒葛软胶囊溶出度的研究

目的:建立椒葛软胶囊体外溶出度及测定方法。方法:以0.1M盐酸胃蛋白酶溶液900ml为介质,转速为200r/min;采用HPLC法测定椒葛软胶囊的体外溶出度。结果:在60分钟椒葛软胶囊的溶出度均大于标示量(70%)。结论:该法测定椒葛软胶囊的溶出度,方法稳定、可行。     

盐酸奥洛他定片处方及制备工艺研究

目的:考察及筛选盐酸奥洛他定片的处方及制备工艺。方法:通过系列试验筛选崩解剂用量、片剂硬度、粉末直接压片和湿法制粒工艺、主要与辅料混合工艺等条件,确定处方及制备工艺。结果:确定了盐酸奥洛他定片的处方和制备工艺,崩解剂交联羧甲基纤维素钠用量为5%,采用等量递加法混合后湿法制粒,控制片剂硬度在40N-50N之间压片,薄膜包衣,即得。结论:盐酸奥洛他定片的处方合理、工艺可行,符合片剂的质量标准。     

Box-Behnken响应面法优化金线莲颗粒成型工艺

以填充剂种类、辅料配比、原料用量、干燥温度和黏合剂用量为考察因素,以颗粒合格率、溶化性、吸湿性和感官评价的总评归一值(OD)作为评价指标,采用单因素实验并结合响应面优化设计优选金线莲颗粒剂最佳成型工艺。结果表明,最佳成型工艺为辅料乳糖:糊精=3:1,原料药比例7.01%、干燥温度50 ℃,按此方案进行试验,预测颗粒成型率87.18%,吸湿率8.22%,溶化时间34.95 s,感官评价81分。采用响应面法优化金线莲颗粒的成型工艺结果可靠,可为金线莲颗粒剂的工业化生产提供依据。     

盐酸头孢卡品酯片溶出度试验方法的建立

目的:建立盐酸头孢卡品酯片溶出度试验方法,为本品质量控制提供参考依据。方法:依据相关文献和指导原则,用原研产品进行试验,根据实验结果确定溶出度参数。结果:确定溶出装置、转速、溶出主介质和检测波长、检测仪器,最终确定取样时间点,规定限值。结论:建立的盐酸头孢卡品酯片溶出度试验方法是可行的。     

朝鲜蓟提取物颗粒剂的制备工艺研究

以单因素试验为基础，采用正交实验设计优化制备朝鲜蓟(Cynara scolymus)提取物颗粒剂的最佳工艺条件。以原料与辅料配比、原料药比例、乙醇浓度及干燥温度为考察因素，以颗粒合格率、溶化时间作为评价指标，采用L₉(3⁴)正交试验分别对颗粒合格率、溶化时间进行直观分析及方差分析。结果表明，最佳成型工艺为乳糖:糊精=3:1，乙醇浓度60%，原料药比例7.0%，干燥温度50 ℃。按此方案进行验证实验，颗粒性状良好，颗粒合格率为91.45%，含水量4.90%，减失重量不超过2.0%，溶解时间85.67 s，均符合2020年中国药典有关规定。通过正交试验优选的颗粒剂制备工艺稳定、简便易行，为朝鲜蓟提取物的剂型开发及工业化生产颗粒剂提供理论依据。     

食用菌调味品造粒工艺研究

应用压力成型法、搅拌法和沸腾法对食用菌调味品进行造粒,并对制成的颗粒的成型率、颗粒外观、粒度分布、吸湿性和流动性等有关指标进行评价和比较。结果表明,造粒后颗粒成型率达到90%以上,临界相对湿度达到53%以上,比粉状原料防潮性能更强。压力成型法所制颗粒的成型率、吸湿性和流动性均为最好,在3种造粒方法中最适于食用菌调味品的造粒生产。     

ATP-linked monomer-polymer equilibrium of smooth muscle myosin: the free folded monomer traps ADP.Pi.

In vitro and at physiological ionic strength, unphosphorylated smooth muscle myosin filaments dissolve on addition of ATP, forming folded (10S) myosin monomers. By following the fate of ATP and the time course of filament disassembly we have established details of the mechanism of this process. Myosin filaments first bind and hydrolyse 2.0 mol/mol of ATP before significant filament dissolution occurs. Following dissolution, the hydrolysis products ADP.Pi are retained on the heads of the folded myosin monomers, and are released so slowly (half time approximately 100 min at 100 mM KCl) as to be effectively trapped. The straight (6S) conformation of myosin, stable at greater than 225 mM KCl, did not exhibit this product trapping, and neither did myosin filaments held under conditions which disfavour ATP-induced disassembly. The implications of these results for filament stability in vivo are discussed in terms of a simple, testable model for smooth muscle myosin self-assembly.     

An Optimized and Feasible Preparation Technique for the Industrial Production of Hydrogel Patches

For hydrogel patches, the laboratory tests could not fully reveal the existing problems of full scale of industrial production, and there are few studies about the preparation technique for the industrial manufacturing process of hydrogel patches. So, the purpose of this work was to elucidate the effects of mainly technological operation and its parameters on the performance of hydrogel patches at the industrial-scale production. The results revealed the following: (1) the aqueous phase was obtained by polyvinylpyrrolidone (PVP) along with tartaric acid dissolved in purified water, then feeding this into a vacuum mixer as a whole in one batch, thus extended the crosslinking reaction time of hydrogel paste (matrix) and allowed the operation of coating/cutting-off to be carried out easily, and there was no permeation of backing layer; (2) the gel strength of the hydrogel patches increased with the increase of working temperature, however, once the temperature exceeded 35 ± 2 °C, the hydrogel paste would lose water severely and the resultant physical crosslinking structure which has lower gel/cohesive strength would easily bring gelatinization/residues during application; (3) the relative humidity (RH) of the standing-workshop was dynamically controlled (namely at 35 ± 2 °C, keeping the RH at 55 ± 5% for 4 days, then 65 ± 5% for 2 days), which would make patches with satisfactory characteristics such as better flexibility, higher adhesive force, smooth flat matrix surface, and without gelatinization/residues and warped edge during the using process; (4) the aging of the packaged hydrogel patches was very sensitive to storage temperature, higher temperature, higher gel strength and lower adhesiveness. The storage temperature of 10 ± 2 °C could effectively prevent matrix aging and adhesion losing, which would also facilitate the expiration date of patches extended obviously. In conclusion, this work provides an optimized and feasible preparation technique for the industrial production of the hydrogel patches and establishes the hydrogel patches as a novel carrier for transdermal drug delivery.     

Porous Starch: a Novel Carrier for Solubility Enhancement of Carbamazepine

To circumvent the solubility-related issues associated with Biopharmaceutics Classification System class II drugs, a novel porous carrier has been developed. In the present study, a process for preparation of porous starch (PS) is demonstrated. The process briefly comprises of translucent gel preparation followed by solvent replacement, drying, and sizing. Carbamazepine (CBZ) was used as a drug candidate to exhibit solubility enhancement potential of PS. PS and CBZ-loaded PS (CBZ-PS) systems were characterized with respect to IR, DSC, XRD, SEM, and dissolution kinetic studies. PS-CBZ was found to follow a Fickian behavior during dissolution. In vivo studies conducted in mice displayed a superior performance of CBZ-PS as compared to neat CBZ.     

Fine mapping of secondary structures of fd phage DNA in the region of the replication origin.

A synthetic heptaribonucleotide, GACCCCC, which is complementary to a unique site on fd bacteriophage DNA, primes DNA synthesis of fd by T4 bacteriophage DNA polymerase. The rate of the GACCCCC-primed DNA synthesis was not uniform as reflected by the appearance of discrete DNA fragments as replication intermediates on an alkaline agarose gel. After 10 minutes of synthesis a significant fraction of the DNA product ran as a single band with a length of about 1960 nucleotides. We have isolated this DNA fragment, hybridized back to unlabeled fd DNA template, and mapped the Taq I restriction fragments by urea polyacrylamide gel electrophoresis. This fine mapping procedure has located two major pause sites at fd nucleotide positions 5575 and 5674. These sites reside in the stem of two very stable hairpin helices near the origin of DNA replication of fd. Models for the functional roles of these two hairpin helices are presented.     

Two-Step Solid Lipid Extrusion as a Process to Modify Dissolution Behavior

Extrudates based on varying ratios of the triglyceride tripalmitin and the hydrophilic polymer polyethylene glycol as matrix formers were produced as oral dosage forms with controlled release characteristics. The extrudates were processed below the melting points of the excipients and contained the hydrophobic model drug chloramphenicol. The influence of the ratio of the matrix formers on drug dissolution was investigated, with an increase in the water-soluble polymer content increasing the drug release rate. In addition, the effect of varying the extrusion process on the extrudate structure and drug dissolution was investigated. Two-step extrusion was performed, which comprised an initial extrusion step of drug and one matrix component followed by milling these extrudates and a second extrusion step for the milled extrudates mixed with the second matrix component. Initial extrusion with polyethylene glycol led to increased dissolution rates, while initial extrusion with tripalmitin led to decreased dissolution rates compared to the dissolution characteristics of extrudates containing the same composition produced by one-step extrusion. Thus, two-step solid lipid extrusion can successfully be used as a process to modify the dissolution behavior of extrudates.     

抗金黄色葡萄球菌卵黄抗体的制备及活性研究

目的:制备金黄色葡萄球菌特异性卵黄抗体并考察其活性。方法:采用灭活的金黄色葡萄球菌免疫产蛋母鸡,通过水稀释法、硫酸铵和硫酸钠盐析及凝胶过滤法分离、纯化抗体。抗体效价测定及体外抑菌试验分别采用酶联免疫吸附法(ELISA)和液体培养基比浊法。结果:纯化所得抗体纯度达95.10%,回收率为20.08%。抗体对金黄色葡萄球菌具有特异性,效价最高可达1:6400。体外抑菌试验表明,抗体抑菌活随IgY浓度的增加而增强,当特异性IgY的浓度为10mg/ml时,能完全抑制细菌生长。结论:抗体制备及纯化所述方法简便、可行,所制抗体具有特异性和抑菌活性。     

以玻璃酸钠为载体改进利福平滴眼液的配制方法

目的:改进利福平滴眼液的配制方法。方法:以计算量的盐酸溶解利福平,然后用等摩尔量的氢氧化钠中和,生成等处方量的氯化钠;并以玻璃酸钠为载体,配制利福平滴眼液。结果:该滴眼液质量稳定、可控,对眼睛无刺激性。结论:本办法设计巧妙,切实可行,既克服了的利福平的溶解困难,又解决了用乙醇作溶剂所产生的眼睛刺激性问题。     

Polyacrylamide gels copolymerized with active esters. A new medium for affinity systems.

A new and versatile method for linking biologically active ligands to a polyacrylamide matrix is reported. Active esters of acrylic acid (N-succinimicyl acrylate and N-phthalimidyl acrylate) were synthesized, then copolymerized with acrylamide and N,N'-methylenebisacrylamide. Displacement of the active ester in the gel thus formed by various ligands containing aliphatic amino groups resulted in the formation of stable amid bonds between the ligands and the polyacrylamide gel. The affinity gel thus prepared has the following advantages: (i) resistance to chemical and microbiological degradation, (ii) ease of control of ligand level and higher levels of ligand possible, (iii) ease of control of porosity, and (iv) total displacement of the active ester under suitable conditions. Efficacy of this system was tested by preparation of 6-aminohexyl 2-acetamido-2-deoxy-beta-D-glucopyranoside derivative polyacrylamide gel by the described method. It was found to be more effective for purification of wheat germ agglutinin than the previously published affinity chromatography systems and the wheat germ hemagglutinin was obtained in crystalline form.In addition, partial resolution of isolectins was obtained from the affinity gel witha pH gradient.