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。     

O 羧甲基壳聚糖抑菌作用研究

目的考察自制O 羧甲基壳聚糖（O CMC）的抑菌活性及其影响因素。方法以金黄色葡萄球菌、枯草芽孢杆菌、大肠埃希菌、铜绿假单胞菌为标准菌株,采用菌落计数法计算抑菌率,比较羧甲基不同取代位置、不同浓度、不同pH对O CMC抑菌效果的影响。结果O CMC抑菌作用强于N, O 羧甲基壳聚糖和N 羧甲基壳聚糖;O CMC的抑菌作用与浓度、pH和供试菌种类有关。在一定范围内,其抑菌效果随浓度增大而加强,随pH增加而减弱;O CMC对革兰阳性菌的抑制作用强于革兰阴性菌。结论该O CMC具有广谱抗菌活性。     

壳聚糖及其衍生物体外抗幽门螺杆菌作用及影响因素

目的研究壳聚糖及其衍生物在体外对幽门螺杆菌(Hp)的抑菌作用及其影响因素。方法采用打孔法检测了不同浓度、pH值、脱乙酰度壳聚糖及羧甲基壳聚糖在体外对Hp的抑菌作用。结果①壳聚糖和羧甲基壳聚糖在体外对3株Hp标准菌株具有普遍的抑菌作用;②在pH 6~4范围内,随pH值降低,抗菌作用增强,差异有显著性(P<0.01),最佳pH值为4;③70%、88.5%脱乙酰度壳聚糖及羧甲基壳聚糖的抗Hp作用差异有显著性(P<0.01~0.05),抑菌强度依次为DD70壳聚糖、DD88.5壳聚糖和羧甲基壳聚糖;④在质量浓度为10 g.L-1~50 g.L-1范围内羧甲基壳聚糖抗Hp作用差异无显著性;在质量浓度为5 g.L-1~20 g.L-1范围内70%、88.5%脱乙酰度壳聚糖抗Hp作用差异也无显著性(P>0.05)。结论①壳聚糖和其衍生物对Hp有普遍的抑菌作用;②壳聚糖及其衍生物的抗Hp作用受多种因素影响,其中pH值对壳聚糖抗菌作用的影响最为明显,在pH值6~4范围内,壳聚糖的抗菌活性随着pH值的下降而增强;③壳聚糖的脱乙酰度、结构(化学修饰)及分子量也影响壳聚糖的抗菌活性,不同的细菌所要求的脱乙酰度、修饰基团和分子量有着明显的差异。     

羧甲基-β-环糊精取代度对毛细管电泳手性拆分的影响

目的:研究羧甲基-β-环糊精取代度对毛细管电泳手性拆分影响。方法:以氯醋酸为羧甲基化试剂,通过调整物料比例合成了3种不同取代度的羧甲基-β-环糊精,并通过核磁共振直接对它们的平均取代度和取代位置进行表征;以萘哌地尔和吲哒帕胺为模型化合物,考察了不同取代度的羧甲基-β-环糊精对毛细管电泳手性拆分的影响。结果:随着羧甲基-β-环糊精取代度的增大,萘哌地尔分离随之改善;相反,吲哒帕胺对映体在较低取代度的羧甲基-β-环糊精条件下获得良好分离。结论:羧甲基-β-环糊精的取代度对毛细管电泳手性拆分和运行缓冲液的离子强度有重要影响,因此在手性分离中使用表征清晰的环糊精衍生物是至关重要的。     

O-羧甲基壳聚糖制备工艺研究

本文以壳聚糖为原料,运用苯甲醛与氨基的席夫碱反应来保护壳聚糖C₂位氨基的方法制备了O-羧甲基壳聚糖(O-CMC)。以产品的收率、取代度为指标,通过单因素实验研究了碱浓度,氯乙酸与苯甲醛化的壳聚糖的质量比,温度对羧甲基反应的影响。结果显示,其最佳反应条件为：25%的NaOH溶液,氯乙酸/苯甲醛化的壳聚糖的质量比为2.8,反应温度为70℃。     

不同取代羧甲基壳聚糖体外酶降解的研究

目的:研究不同取代羧甲基壳聚糖(CMC)的生物降解性.方法:通过体外酶解试验,用粘度测定法研究了在溶菌酶作用下CMC的分子量.结果:溶菌酶作为催化CMC降解的非专一性酶,能有效地催化CMC降解;酶解反应程度与酶浓度成线性关系;随着羧甲基壳聚糖取代度的增加,CMC的降解速度加快.结论:通过控制取代度,可以得到不同生物降解要求的羧甲基壳聚糖.     

羧甲基壳聚糖-Co(II)配合物与鲱鱼精DNA的相互作用

目的 研究了羧甲基壳聚糖-Co(II)配合物与鲱鱼精DNA之间的作用方式。方法 采用循环伏安法和光谱法研究了羧甲基壳聚糖-Co(II)配合物与鲱鱼精DNA之间的作用机制。结果 (1) 羧甲基壳聚糖-Co(II)的存在导致Fe(CN)63-/4-探针分子氧化还原峰电流下降,峰值电位正移,显示羧甲基壳聚糖-Co(II)和Fe(CN)63-/4-与DNA之间存在竞争性作用。(2) 随着DNA的不断加入,羧甲基壳聚糖-Co(II)的特征吸收峰强度逐渐降低,峰位红移;同时,中性红的加入导致羧甲基壳聚糖-Co(II)/DNA体系的特征吸收峰发生增色效应、峰位红移并伴有等吸收点出现,表明羧甲基壳聚糖-Co(II)、DNA与中性红三者存在新的共平衡体系,中性红对羧甲基壳聚糖-Co(II)与DNA的作用有竞争抑制作用。结论 羧甲基壳聚糖-Co(II)能够以嵌插方式与鲱鱼精DNA发生相互作用。     

O-羧甲基壳聚糖稳定性研究

目的考察自制O 羧甲基壳聚糖（O CMC）的稳定性。方法采用旋转黏度计测定O CMC的特性,黏度作为稳定性考察指标,比较O CMC在不同pH、不同离子强度、紫外线照射、温度等条件下的稳定性。结果O CMC的特性黏度随pH的降低而降低;溶液离子强度越大,O CMC特性黏度越小;随紫外线照射时间的延长,O CMC的特性黏度逐渐变小;随37 ℃培养条件下应用时间延长,O CMC特性黏度逐渐降低。结论酸碱度、离子强度、紫外线照射、温度对O CMC的稳定性均有较大影响。     

添加羧甲基壳聚糖的藻酸盐印模材料抗菌性能研究

目的对添加羧甲基壳聚糖的藻酸盐印模材料的抗菌性进行测试,为口腔抗菌印模材的研究提供参考。方法分别以不同的添加比将不同取代位置、取代度、相对分子质量和脱乙酰度的羧甲基壳聚糖加入藻酸盐印模材料中,采用薄膜密着法,分别测试添加抗菌成分后印模材料对大肠杆菌、金黄色葡萄球菌的抗菌活性。结果O-羧甲基壳聚糖的抗菌性较好,O-羧甲基壳聚糖分别以1%和1.4%的添加比添加到藻酸盐印模材料中,对大肠杆菌和金黄色葡萄球菌有最好的抗菌性。随着脱乙酰度的提高,抑菌率均可达到99.99%。结论添加羧甲基壳聚糖的藻酸盐印模材料具有良好的抗菌效果。     

水溶性O-羧甲基壳聚糖的制备及结构表征

目的:以甲壳素为原料制备水溶性O-羧甲基壳聚糖(O-CMC),并进行结构表征.方法:通过羧甲基化和脱乙酰化两步反应合成O-CMC,采用胶体滴定法测定产物的取代度和脱乙酰度,一点法测定黏均分子量,利用红外谱图确定羧甲基的取代位置.结果:甲壳素与氯乙酸在50℃进行羧甲基化反应4h,然后于50℃碱性条件下进行脱乙酰化反应30 min,即得产物.经超声纯化,制得水溶性O-CMC,产率为78.14％.红外光谱分析表明,合成产物的羧甲基仅局限于C6伯羟基取代,取代度为0.64,脱乙酰度为44.53％,黏均分子量为1.42×104.O-CMC在中性和碱性条件下水溶性好,等电点为4.46,0.5％水溶液pH为7.52.结论:本法制得的O-CMC结构表征明确,脱乙酰度和取代度符合设计要求,水溶性佳.     

Counter-ion binding to mucus glycoproteins

The affinity of pig gastric mucus glycoprotein for counter ions of various valencies was examined. Ions of higher valency were bound with increasing avidity, but the degree of binding was apparently not influenced by the ionic radius. The affinity of the glycoprotein for the ions studied may be ranked: Fe3+ greater than Al3+ greater than Ca2+ greater than Cs+ congruent to Na+. The binding of calcium was inhibited by high ionic strength and was sensitive to the pH of the environment. Enzymatic removal of sialic acid slightly reduced the calcium binding capacity.     

Gastric resistant microbeads of metal ion cross-linked carboxymethyl guar gum for oral drug delivery

Ionic cross-linking of sodium carboxymethyl guar gum as a mild method for microencapsulation of sensitive drugs, like proteins, is presented. When a solution of sodium salt of carboxymethyl guar gum, containing BSA as a model drug, is added, as droplets, to different multivalent metal ion solutions, they get cross-linked to form insoluble microbeads. The amount of protein retained, morphology of the resulting beads and the subsequent release of the retained protein is simulated intestinal fluids varied with the type of metal ion as well as it's concentration. Trivalent metal ions like Al+++ and Fe+++ were found to be superior to divalent metal ions like Ba+ +, Ca++, Cu++ and Cd++. The optimum concentration around which these ions provide maximum drug retention was found to be much lower for trivalent ions. Beads cross-linked with them released the protein over a longer duration in enzyme free simulated intestinal fluid, than those cross-linked with divalent ions. Mg++, Sr++, Co++ and Zn++ failed to form isolable beads.     

Kinetics and mechanism of chlorambucil hydrolysis.

The kinetics and mechanism of hydrolysis of the cytotoxic drug chlorambucil were investigated. A study of the reaction order and of the pH, dielectric constant, and ionic strength effects on the reaction rate revealed that the hydrolysis was a limiting unimolecular nucleophilic substitution, the rate-determining step being the ionization of the first 2-chloroethylamine chlorine. The hydrolysis rate was markedly dependent on the protonation degree of the chlorambucil basic group. indicating that a cyclic ethyleneimmonium ion may be involved in the rate-determining step.     

人工肾透析液中氯化钙和氯化镁含量的连续测定

目的 建立人工肾透析液中氯化钙和氯化镁含量的连续测定方法。方法 根据Ca^2＋和Mg^2＋在不同pH值条件下与乙二胺四乙酸二钠（EDTA-Na2）能定量发生络合反应的原理，选择酸性酪蓝K和萘酚绿B为混合络合指示剂（K-B络合指示剂），同时为避免Fe^3＋和Al^3＋金属离子的干扰，加入三乙醇胺和酒石酸联合掩蔽。分别在pH〉12和pH=10的条件下测定高、中、低3种浓度样品溶液中氯化钙、氯化镁的含量。结果 氯化钙和氯化镁平均加样回收率分别为99．7％和99．4％，RSD分别为0．45％和0．44％。结论 该方法简便、灵敏、准确、可靠，可满足临床需要。     

Activation of calmodulin by various metal cations as a function of ionic radius

The active form of calmodulin is a Ca2+ . calmodulin complex. The purpose of this investigation was to determine whether other metal cations substitute for Ca2+ to activate calmodulin. Binding of Ca2+ resulted in an altered conformation of calmodulin with an increased quantum yield in its tyrosine fluorescence. Qualitatively similar results were obtained with Zn2+, Mn2+, Cd2+, Hg2+, Sr2+, Pb2+, Tb3+, Sm3+, and La3+. The relative extents of fluorescence enhancement by these cations were related to their ionic radii: all cations with ionic radii close to Ca2+ (0.99 A) increased tyrosine fluorescence, whereas those with different ionic radii were not effective, or much less so. The change in calmodulin conformation by the cations was confirmed by its altered electrophoretic mobility on polyacrylamide gels. Cations that change the conformation of calmodulin allow it to stimulate phosphodiesterase. The relative extents of stimulation of phosphodiesterase by cations were also related to their ionic radii. Finally, the ability of metal cations to inhibit Ca2+ binding was similarly related to their ionic radii. In general, the closer the radius of a metal cation was to that of Ca2+, the more effective was the cation to substitute for Ca2+. The range of effective ionic radii was approximately 1 +/- 0.2 A. Calmodulin-stimulated phosphodiesterase activity by the cations was reversed by trifluoperazine, an antagonist of calmodulin.     

Gastric resistant microbeads of metal ion cross-linked carboxymethyl guar gum for oral drug delivery

Ionic cross-linking of sodium carboxymethyl guar gum as a mild method for microencapsulation of sensitive drugs, like proteins, is presented. When a solution of sodium salt of carboxymethyl guar gum, containing BSA as a model drug, is added, as droplets, to different multivalent metal ion solutions, they get cross-linked to form insoluble microbeads. The amount of protein retained, morphology of the resulting beads and the subsequent release of the retained protein is simulated intestinal fluids varied with the type of metal ion as well as it's concentration. Trivalent metal ions like Al +++ and Fe +++ were found to be superior to divalent metal ions like Ba ++, Ca ++, Cu ++ and Cd ++ . The optimum concentration around which these ions provide maximum drug retention was found to be much lower for trivalent ions. Beads cross-linked with them released the protein over a longer duration in enzyme free simulated intestinal fluid, than those cross-linked with divalent ions. Mg ++, Sr ++, Co ++ and Zn ++ failed to form isolable beads.     

The development and in-vitro evaluation of novel mixed metal hydroxy-carbonate compounds as phosphate binders

The currently available phosphate binders are relatively inefficient and suffer from clinical side-effects of increased absorption of calcium and aluminium and the diarrhoea-inducing effects of magnesium. A new class of compounds based on mixed metal hydroxides has been developed and evaluated for their potential as phosphate binders. The mixed metal hydroxides were prepared using a standard procedure for hydrotalcite (Al2Mg6(OH)16.CO3.4H2O) by substituting Fe3+ for Al3+, with Mg2+ or Ca2+ as the divalent metal ion. Phosphate precipitation (binding) was examined at different pH values in aqueous solution and in various food mixtures in comparison with hydrotalcite, Al(OH)3, CaCO3 and Mg(OH)2 on the same weight-to-weight basis. A series of compounds with differing ratios of metal ions (Fe:Mg/Ca 1:2 or 1:3) gave analytically similar ratios to those predicted from the initial amounts added. CTFeCa bound > 90% phosphate in aqueous solution compared with 65% binding with CTFeMg, 85% binding with Mg(OH)2, and less than 30% binding for CaCO3 and Al(OH)3. The mixed metal compounds also bound up to 80% phosphate in various food matrices, which was relatively independent of changes in pH, compared with Mg(OH)2, where binding decreased from 85% at pH 3.0 to 25% at pH 8.0. Al(OH)3 and CaCO3 were relatively ineffective phosphate binders under all the conditions tested. The mixed metal hydroxides compounds show considerable promise as phosphate binders over those currently available and warrant further patient-based in-vivo testing.     

复方土金颗粒既驱汞又防止微量元素丢失

目的：统计分析复方土金颗粒驱汞后尿中必需微量元素Ca^2 、Mg^2 、Zn^2 、Fe^3 和Cu^2 的变化。方法：应用冷原子吸收光谱法．测定二巯基丙磺酸钠(DMPS)组(100名病人)、复方土金颗粒组(99名病人)治疗前后尿中微量元素和汞值情况，测定复方土金颗粒组用药前后病人体内电解质情况，并均与对照组比较。观察临床症状和体征。结果：DMPS组除Cu^2 外，其余4种微量元素用药前后均有显著性差异；复方土金颗粒组5种微量元素、电解质在用药前后无显著性差异。结论：复方土金颗粒保护了人体必需微量元素，克服了DMPS组金属络合征等不良反应，可作为一线作业现场的慢性中毒的治疗用药和预防用药。     

Transport Properties of Ionic Drugs in the Ammonio Methacrylate Copolymer Membranes

Purpose. Ammonio methacrylate copolymer is a pharmaceutical excipient widely used as a coating material for encapsulation of pellet and tablet dosage forms. Because of the charged ammonio function groups within the polymer, ionic drugs may interact with the coating film while transporting through it. The kinetic swelling and drug permeation properties of the ammonio methacrylate copolymer membranes were studied to delineate the effect of ionic interaction between the ionic drugs and the membranes. Methods. The pH and ionic strength of the solutions and the charged properties of drugs were varied to study the effects on the transport properties through the membranes. Ambroxol was chosen as a model cationic drug and aspirin as a model anionic drug. Results. The degree of membrane swelling in the drug-free solution decreases as the ionic strength increases but it is irrelevant to the pH. With the presence of ionic drugs, the degree of membrane swelling is affected by the drug species as well as the pH of the solutions in addition to the effect of ionic strength. The degree of swelling for a membrane in a solution containing aspirin is higher at a lower pH and ambroxol is lower at a lower pH. Aspirin experiences a three-stage permeation and ambroxol a two-stage one. The ion-exchange reaction between the anionic carboxylic groups in aspirin and the cationic ammonio groups in the membranes results in a slow permeation stage during the transient state. The pseudo steady-state permeability for each drug follows the trend as the degree of membrane swelling in the drug media at various pH and ionic strengths. However, it is much higher for aspirin than ambroxol although the degree of membrane swelling is higher in an ambroxol solution than that in an aspirin solution. The permeability of ambroxol through the membrane is largely reduced because of the Donnan exclusion effect. Conclusions. The interaction between ionic drugs with the cationic groups in the membranes affects the ionic strength of the solutions and results in a pH-dependent degree of swelling. The ionic interaction also determines the drug permeation rates as well as the transient permeation behaviors.