褐藻胶肠溶胶丸在胃肠中的崩解应用

药物治疗中，口服法是最常使用的投药方法。由于有许多药物对胃肠粘膜有刺激作用，易被胃液破坏，有的药物须在肠道中起作用，才能发挥药物疗效。多年来人们致力于肠溶性和胃不溶性新型胶丸的研制。目前国内外普遍采用的肠港材料[1~3]：如苯二甲酸醋酸纤维、丙烯酸树酯、羟丙基纤维苯二甲酸酯、其肠溶性能不稳定、易老化。为此国家医药总局给厦门鱼肝油厂下达褐藻胶肠溶胶丸（以下简称胶丸）的研制任务，我们就其研制出的胶丸，内置碘油，经口服法经过X线电视录相、定时追踪摄片，进行观察。结果证实胶丸100％于小肠崩解而在胃不崩解，性能…     

海藻多糖褐藻胶生物活性及其应用研究新进展

综述近年来海藻多糖褐藻胶及其修饰产物的生物活性研究及其在医药等领域的应用研究新进展，展望褐藻胶降解产物褐藻胶寡糖的应用前景。     

一株产褐藻酸多糖的海洋假单胞细菌 Pseudomonass P．QDA的筛选和鉴定

根据已获褐藻酸多糖生物合成基因簇中褐藻胶裂解酸基因(algL)的序列设计特异性引物，利用PCR技术从海洋微生物中筛选到1株能够分泌胞外多糖的细菌。采用形态学观察和DNA序列分析鉴定该菌株，结果为假单胞属细菌，命名为Pseudomonassp．QDA；系统发育树显示该菌株与P.purida亲缘关系最近。菌株产生的胞外多糖可被褐藻胶裂解酶(AlgL)降解，并在紫外234nm处检测到特征性吸收，初步证明含有褐藻酸多糖。     

羧甲基茯苓多糖的制备及抗肿瘤活性研究

目的 提取茯苓药材中的多糖,测定其总糖含量,并进行羧甲基化改性,考察茯苓多糖与修饰后的羧甲基茯苓多糖的抗肿瘤活性。方法 采用稀碱浸提法提取茯苓多糖,苯酚-硫酸显色法测定茯苓多糖中总糖含量,通过羧甲基化反应得到羧甲基茯苓多糖。并采用MTT法检测茯苓多糖与羧甲基茯苓多糖对人肝癌细胞HepG-2的毒性反应。结果 苯酚-硫酸法测得茯苓多糖中总糖含量为95.96%,羧甲基茯苓多糖与茯苓多糖对HepG-2细胞的增殖均具有一定的抑制作用,其中羧甲基茯苓多糖活性更强。结论 经过修饰后的羧甲基茯苓多糖具有更好的抗肿瘤活性。     

羧甲基壳聚糖对锌离子的吸附作用研究

本文对羧甲基壳聚糖与Ｚｎ＾２＋的吸附作用进行了研究,探讨了反应时间、离子强度、溶液的ｐＨ值、羧甲基取代度、温度等因素对吸附性能的影响。与水溶性低聚壳聚糖相比。羧甲基壳聚糖具有更强的络合能力。羧甲基壳聚糖－锌络合物可用于生物活性研究,为开发生物多糖型补锌剂提供理论依据。     

褐藻胶作肠溶胶囊材料初步探讨

肠溶胶囊是指在胃中不溶或不崩解,而在肠中可溶或崩解的胶囊。它用来包裹要求不在胃中释放,而到小肠溶解释放的药物。这类药物很多,应用很广。因此,寻找理想的肠溶胶囊材料,是药物制剂研究课题之一。我们在用褐藻胶代明胶制无缝鱼肝油丸胶囊实验中发现,褐藻胶可作肠溶胶囊材料,由它制得的褐藻酸钙胶囊,肠溶性稳定,不论胶囊厚薄,在人工胃液中停留多长时间都不崩解,而在人工肠液中均能很快崩解;久贮不变质;无毒副作用;制备工艺简单,常温下便可滴丸烘干,无需冷房;原材料消耗少,来源丰富,成本低。同时还     

苯酚硫酸法测定兔血浆羧甲基茯苓多糖含量

目的建立兔血浆羧甲基茯苓多糖浓度测定方法。方法对兔血浆样品进行预处理，并用苯酚硫酸法测定羧甲基茯苓多糖的含量，测定波长为488.2 nm。 结果兔血浆羧甲基茯苓多糖血药浓度线性范围为2～64 μg·mL^-1，回归方程为C ＝ 76.667 6A＋0.850 8，r＝0.999 8，回收率≥96.54%，日内精密度RSD≤1.56%，日间精密度RSD≤2.53%。结论该方法操作简便，测定结果准确可靠，可用于羧甲基茯苓多糖的血药浓度测定。     

茯苓碱溶性多糖的理化性质评价及其在双氯芬酸钠缓释片中的应用研究

本研究从茯苓残渣中提取得到茯苓碱溶性多糖,采用傅里叶变换红外光谱法(FTIR)、X-射线粉末衍射法(XRD)、差示扫描量热法分析(DSC)等方法对茯苓碱溶性多糖进行了结构表征,采用电子扫描显微镜(SEM)考察了茯苓碱溶性多糖和乙基纤维素(EC)的物理形貌,并重点考察休止角、松密度、振实密度、卡尔指数、颗粒间孔隙率、内聚力指数、豪斯纳比等指标,绘制粉末物理指纹图谱,采用多元分析法进行粉体学性能评价。采用直接压片法,分别使用茯苓碱溶性多糖和EC为不溶性骨架材料,制备双氯芬酸钠缓释片,评价缓释片的基本性能,考察体外释药行为,并研究其释放机制。结果表明,茯苓碱溶性多糖是一种呈光滑片状结构的半结晶聚合物,堆积性、可压性均强于EC;体外释放实验表明,茯苓碱溶性多糖缓释性能强于EC,其所制备的缓释片释药行为符合Higuchi模型,释放过程中片剂内部形成了孔隙结构,释放方式为孔道扩散释药。该研究结果对新型缓释材料的开发和资源的合理利用具有重要意义。     

3种海藻多糖调血脂作用比较研究

进行了3种工业海藻多糖调血脂作用的比较研究。实验结果证明，3种海藻多糖均具有程度不同的降低受试动物血浆中TC，TG和LDL—C和升高HDL—C的作用，而且与剂量相关。在本实验范围内，降低胆固醇作用卡拉胶效佳(P＜0．001)，降甘油三酯作用褐藻胶效佳(P＜0．001)，升高高密度脂蛋白作用卡拉胶效佳(P＜0．001)，降低低密度脂蛋白作用卡拉胶和褐藻胶均有明显效果(P＜0．001)。     

海洋弧菌QY105中褐藻胶寡糖酶OalA的基因克隆、重组表达与性质研究?

目的 褐藻胶寡糖酶可将褐藻胶多糖和寡糖降解为单糖,但现有的褐藻胶寡糖酶数量极少且活力较差。本文旨在从海洋弧菌QY105中克隆寡糖酶OalA的编码基因,重组表达并研究其酶学性质。方法 利用简并PCR和SiteFinding-PCR从海洋弧菌QY105中克隆得到褐藻胶寡糖酶OalA的编码基因,在大肠杆菌中进行重组表达,对重组酶进行分离纯化及酶学性质研究。结果 褐藻胶寡糖酶OalA基因全长2082 bp,编码一条含有693个氨基酸残基的多肽链,理论分子量为79.17 kDa,理论等电点为4.98,属于多糖裂解酶第15家族（PL-15）。重组OalA比活力为9.2 U?mg?1,最适温度30 ℃,在10 ℃的酶活力达到最高酶活的45%,最适pH7.6,在低于30 ℃和pH6~10范围内稳定,偏好降解polyM。结论 OalA具有低温酶的特点,且对polyM具有偏好性,可用于褐藻胶单糖制备、PL-15家族结构与功能相互关系研究等领域。     

多肋藻(Costaria costata)多糖的提取分离及理化性质分析

目的 从多肋藻(Costaria costata)中提取分离多糖并对其进行理化性质分析.方法 采用水和2%碳酸钠水溶液于85℃提取多糖,采用高效凝胶渗透色谱法(HPGPC)分析多糖相对分子质量,用核磁共振氢谱(<'1>H-NMR)法分析褐藻胶中M/G比,用高效液相色谱法(HPLC)分析褐藻糖胶单糖组成.结果 从多肋藻中...     

羧氨基葡聚多糖钠生物胶体液无菌检查法的建立

目的:建立羧氨基葡聚多糖钠生物胶体液的无菌检查方法。方法:采用薄膜过滤法,对样品中金黄色葡萄球菌、大肠埃希菌、枯草芽孢杆菌、生孢梭菌、白色念珠菌、黑曲霉生长情况进行考察;对受抑制的试验菌(生孢梭菌、白色念珠菌)采用加热冲洗液的方法消除样品对其的抑制作用并进行验证。结果:羧氨基葡聚多糖钠生物胶体液对生孢梭菌的抑菌作用最强;采用加热至45℃的0.1%无菌蛋白胨水溶液500mL(每膜)冲洗可消除其抑菌作用,验证试验中试验菌生长良好。结论:所建立的方法可用于羧氨基葡聚多糖钠生物胶体液的无菌检查,且结果准确、可靠。     

苯酚滴耳液微生物限度检查方法的建立与验证

目的建立苯酚滴耳液微生物限度检查方法,并进行验证。方法按中国药典2010年版,采用常规法、薄膜过滤法和中和法对苯酚滴耳液进行抑菌活性试验,计算每次试验的回收率。结果采用薄膜过滤法联合中和剂,且冲洗量为500 m L时,可使大肠埃希菌、枯草芽孢杆菌和金黄色葡萄球菌的回收率均>70%;采用常规法联合中和剂,可使白色念珠菌和黑曲霉的回收率均>70%。结论苯酚滴耳液具有抑菌活性,薄膜过滤法联合中和剂适用于苯酚滴耳液细菌计数检验;常规法联合中和剂适用于苯酚滴耳液霉菌和酵母菌计数检验以及控制菌检查。     

The antimicrobial activity of vancomycin in the presence and absence of sodium carboxymethyl starch

The purpose of this work was to determine any effects the presence of sodium carboxymethyl starch may have on the antimicrobial activity of vancomycin given a previously described interaction between vancomycin and sodium carboxymethyl starch. In particular, the in-vitro activity of vancomycin against two clinically relevant bacteria, Staphylococcus aureus and Enterococcus faecalis, was studied in the presence of varying concentrations of sodium carboxymethyl starch. From two independent studies conducted using an agar dilution method, it appeared that the binding of vancomycin to sodium carboxymethyl starch had no effect on the in-vitro antimicrobial activity of vancomycin. The minimum inhibitory concentration of vancomycin against S. aureus in the presence of as much as 1 mg mL(-1) sodium carboxymethyl starch was similar to that of the control where no sodium carboxymethyl starch was added (1-4 microg mL(-1) vs 1-2 microg mL(-1), respectively). Likewise, the minimum inhibitory concentration of vancomycin against E. faecalis in the presence of 1 mg mL(-1) sodium carboxymethyl starch was also similar to that of the control where no sodium carboxymethyl starch was added (1-4 microg mL(-1) vs 1-4 microg mL(-1), respectively). However, there may be factors in the in-vitro method, such as high ionic strength, that could disrupt the interaction between vancomycin and sodium carboxymethyl starch. Therefore, the possibility of diminished vancomycin activity in-vivo cannot be ruled out. A small percentage (8-10%) of vancomycin was determined to be bound to sodium carboxymethyl starch in broth media. Given these results, the impact of sodium carboxymethyl starch on the in-vitro antimicrobial activity of vancomycin is expected to be minimal. Binding studies could not be conducted with gelled agar due to its semi-solid state.     

Enantiomer separation by capillary electrophoresis utilizing carboxymethyl derivatives of polysaccharides as chiral selectors.

Enantiomer separations of various drugs by capillary electrophoresis (CE) were investigated utilizing carboxymethyl (CM) derivatives of some polysaccharides. Three types of CM-polysaccharides, namely CM-dextran, -amylose and -cellulose were employed as chiral selectors in the CE enantiomer separation. Capability of enantiomer separation by these CM-polysaccharides was compared with that by polysaccharides without CM residues (i.e. native or neutral polysaccharides). Among three selectors employed, CM-dextran and -cellulose showed a relatively wide capability of enantiomer separation. Modification of polysaccharides seems to lead to the enhancement of the capability of enantiomer separation. Degree of substitution greatly affected the capability of enantiomer separation of these polysaccharide derivatives as in the beta-cyclodextrins derivatives.     

Method for testing the sterility of total nutrient admixtures

A test for determining the sterility of a total nutrient admixture (TNA) containing equal quantities of 10% fat emulsion (Liposyn II), 8.5% amino acids injection, and 50% dextrose injection using the USP membrane filtration procedure was developed and evaluated. Membrane filter selection was determined by analysis of flow rates, membrane fluid compatibility, bubble point stability, and rinse fluid requirements. Microbial challenges employing five organisms (Bacillus subtilis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) and both soybean casein digest and fluid thioglycollate media were used to confirm the ability of the test to detect low-level microbial contamination. A polyvinylidene fluoride membrane was determined to be the most appropriate of the membrane types studied because of its superior flow rate and membrane-fluid compatibility. Bubble point testing revealed no detrimental effects on the membrane. The potential problem of haziness caused by retention of the TNA by the membrane with subsequent release in the culture media (which could result in false-positive growth determinations) was diminished by using a sterile 0.1% peptone solution rinse and careful observation techniques. Performance of the sterility test by six hospital pharmacists required an average of 14.2 minutes. Sterility testing of alternate TNAs compounded with Intralipid and Nutralipid was not feasible because of prolonged filtration times. The basic USP membrane filtration procedure for large-volume injections can be used by hospital pharmacists for testing the sterility of TNAs. When fat emulsions are used in compounding, sterility-testing procedures specific to the emulsion product used should be developed and evaluated.     

NMR imaging of chitosan and carboxymethyl starch tablets: swelling and hydration of the polyelectrolyte complex

The hydration and swelling properties of the tablets made of chitosan, carboxymethyl starch, and a polyelectrolyte complex of these two polysaccharides have been studied by NMR imaging. We studied the effect of pH and ionic strength on the swelling of the tablets and on the diffusion of fluid into the tablets in water and simulated physiological fluids. The pH value of the fluids exerts a more significant effect than their ionic strengths on the swelling of the tablets. The tablets are compared also with those made of cross-linked high amylose starch. The formation of complex helps to keep the integrity of the tablets in various media and render a slow and restricted swelling similar to that of the tablets of the cross-linked high amylase starch, which is significantly lower than the swelling of chitosan and of carboxymethyl starch. The capacities to modulate the release rate of drugs in different media are discussed by comparing the matrices and evaluating the preparation process of the complex. A sustained release of less soluble drugs such as aspirin in gastrointestinal fluids can be provided by the complex, due to the ionic interaction and hydrogen bonding between the drug and the biopolymer complex.     

褐藻胶对大鼠实验性肝纤维化的防治作用

褐藻胶是海藻的提取物，本文研究了四氯化碳诱导的大鼠肝纤维化模用褐藻胶后肝脏组织学和血清ＰＣⅢ和ＨＡ水平变化。结果表明，褐藻胶对实验性肝纤维化有一定的防治作用。     

几种海洋类肝素多糖的制备及抗乙肝病毒活性初步研究D

目的　制备具有类肝素结构的海洋硫酸多糖,采用HepG2.2.15细胞模型评价它们的体外抗HBV活性。方法 以聚甘露糖醛酸(PM)、聚古罗糖醛酸(PG)和壳寡糖(COS)、甲壳素(CTN)及羧甲基壳聚糖(CMC)为原料,采用氯磺酸-甲酰胺法制备相应的多糖硫酸酯PMS、PGS、SCOS、SCTN和SCMC,并对其硫酸根含量、分子量等理化性质进行测定。以HepG2.2.15细胞为模型,采用MTT法检测多糖的细胞毒性,采用ELISA法检测培养上清中的HBsAg和HBeAg。结果 几种海洋类肝素多糖在30,60,125,250 μg/mL浓度下,对HepG2.2.15细胞作用9d后,均能明显抑制HBsAg和HBeAg的分泌,其中 PGS和PMS的抗HBV活性优于3种壳聚糖硫酸酯衍生物。结论　不同结构的海洋类肝素多糖对HBV抗原具有不同程度的抑制作用,PGS和PMS在抗HBV方面具有潜在的应用前景。