羧甲基壳聚糖体外抗幽门螺杆菌作用的研究

目的研究羧甲基壳聚糖体外对Hp的抑菌作用,为其体内应用提供理论和实验依据。方法①将羧甲基壳聚糖溶于不同浓度乙酸溶液中,得到不同pH值和浓度的溶液。②采用打孔法检测羧甲基壳聚糖溶液对Hp菌株的抑菌作用,并分别做对照。结果①羧甲基纤维素及乙酸对照液对Hp无抗菌作用。②羧甲基壳聚糖在pH值为6和5时无抗Hp作用,只在pH为4时有抗Hp作用,相比之下差异显著（P〈0.01）;羧甲基壳聚糖抗Hp作用存在菌株间差异（P〈0.01或P〈0.05）。③在1%～5%浓度范围内羧甲基壳聚糖抗Hp作用无显著差异。结论①羧甲基壳聚糖对Hp有普遍抑菌作用,可望成为一种新型的抗Hp药物。②其抗Hp作用受pH值影响最为明显。     

壳聚糖抗幽门螺杆菌的实验研究

目的研究壳聚糖在不同浓度和不同pH条件下对幽门螺杆菌 (Hp)的抑菌作用 ,为壳聚糖的临床应用提供实验依据。方法采用打孔法检测不同浓度和不同pH值壳聚糖对Hp标准菌株SS1和两株患者体内分离出的Hp菌株的抑菌作用。结果壳聚糖对 3种Hp菌株均有抑菌作用 ,且在 3株不同Hp菌株间无差异 (P >0 .0 5 ) ;在pH8.5～ 5 .5范围内 ,随着pH值降低 ,壳聚糖的抗Hp作用增强 (P <0 .0 1 ) ;不同浓度的壳聚糖对Hp的抑菌作用有非常显著差异 (P <0 .0 1 ) ,在 4 %时达高峰。结论壳聚糖在体外对Hp有抑菌作用 ,并且此作用在酸性条件下明显加强 ,这尤为适应胃内的酸性环境     

壳聚糖衍生物对异丙肾上腺素诱导的H9c2心肌损伤的保护作用

目的 探究5种壳聚糖衍生物对大鼠心肌细胞的保护作用。方法 在5种壳聚糖衍生物对大鼠心肌细胞H9c2的细胞形态学和生长增值研究基础上,通过建立H9c2细胞异丙肾上腺素损伤模型,研究5种壳聚糖衍生物对损伤H9c2细胞的保护作用。结果 N-乙酰氨基葡萄糖、磺酸化壳寡糖、低脱乙酰度壳寡糖、高脱乙酰度壳寡糖、羧甲基壳聚糖均能不同程度地促进H9c2细胞的生长,对损伤H9c2细胞均有保护和增殖促进作用,N-乙酰氨基葡萄糖、磺酸化壳寡糖、低脱乙酰度壳寡糖、高脱乙酰度壳寡糖的最佳作用浓度均为50 μg?mL-1,羧甲基壳聚糖的最佳作用浓度为100 μg?mL-1。     

鼻用氟脲嘧啶壳聚糖微球的体外释放及溶胀影响因素

目的考察壳聚糖脱乙酰度、壳聚糖浓度、固化剂用量、固化时间以及介质pH值对氟脲嘧啶壳聚糖微球的体外释放与溶胀的影响。方法乳化化学交联法制备氟脲嘧啶鼻用微球,动态透析法检测微球的体外释放特性;根据微球吸水前后质量变化测定微球的溶胀率。结果壳聚糖的脱乙酰度越高、固化剂用量越大、固化时间越长则微球的溶胀越慢,微球的体外释放越慢;壳聚糖浓度的增加则使微球的溶胀度增加,体外释放量减少;释放介质的pH值对微球的溶胀性能影响很大,在酸性条件下微球溶胀度高且释药加快。结论影响壳聚糖微球溶胀的因素顺序为介质的pH值>固化剂用量>固化时间>壳聚糖浓度≈壳聚糖脱乙酰度;影响壳聚糖微球体外释放的因素顺序为固化剂用量>壳聚糖脱乙酰度>壳聚糖浓度,而固化时间和介质的pH值对体外释放无显著性影响。     

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。     

复方大青叶注射液体外抑菌作用及抗内毒素作用的研究

目的研究复方大青叶注射液体外抑菌作用及抗内毒素作用。方法体外抑菌作用采用液体培养基连续稀释法测定复方大青叶的最小抑菌浓度(MIC);抗内毒素作用采用细菌内毒素检查法。结果体外抑菌实验结果表明复方大青叶注射液对被测微生物的最小抑菌浓度为:金黄色葡萄球菌,MIC62 g.L-1;藤黄微球菌,MIC62 g.L-1;枯草芽孢杆菌,MIC62 g.L-1;大肠埃希菌,MIC125 g.L-1;变形杆菌,MIC125 g.L-1;新型隐球菌,MIC62 g.L-1;白假丝酵母菌,MIC125 g.L-1;啤酒酵母菌,MIC125 g.L-1。抗内毒素结果:复方大青叶注射液62 g.L-1即具有抗内毒素作用。结论复方大青叶注射液体外具有广谱抗菌作用,不仅对革兰阳性细菌有较强的抑菌作用,而且对某些真菌也有较强的抑菌作用;复方大青叶注射液有较强的抗内毒素活性。     

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。     

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.     

不同分子量和脱乙酰度壳聚糖用作组织工程材料的性质评价

目的对不同相对分子质量(Mr)和脱乙酰度的壳聚糖用于组织再生修复的前景进行评价。方法MTT法测定Mr为5万,20万,50万,100万,脱乙酰度分别为85%和95%的8种壳聚糖对骨髓间充质干细胞的亲和性,测定它们在体外、体内的降解特性,并通过检测接触角考察了它们的亲水性。结果在所研究的8种壳聚糖中,Mr为50万和100万,脱乙酰度为95%的壳聚糖更利于骨髓间充质干细胞的黏附生长,亲水性较强,在体内埋植8~16周后仍能保持形态完整,利于种子细胞生存。结论Mr为50万和100万,脱乙酰度为95%的壳聚糖能够与骨髓间充质干细胞复合用于组织再生修复。     

低分子量壳聚糖衍生物促胰岛细胞增殖作用的研究

目的探讨低分子量壳聚糖衍生物对胰岛β细胞的促增殖作用。方法在细胞水平上,通过细胞形态学观察和MTT法,研究3种低分子量壳聚糖衍生物对胰岛β细胞系RIN-m5f的促增殖作用。结果低分子量50%D.D.壳聚糖(LM-50%D.D.CTS)、低分子量羧甲基甲壳素(LM-CMC)、低分子量磺酸化壳聚糖(LM-SCTS)对于胰岛β细胞具有明显促增殖作用,其最适作用浓度分别为500,250,500mg.L-1。结论3种低分子量壳聚糖衍生物对于胰岛β细胞系体外增殖具有明显的促进作用。     

Chitosan and its derivatives in mucosal drug and vaccine delivery.

Numerous studies have demonstrated that chitosan and their derivatives (N-trimethyl chitosan, mono-N-carboxymethyl chitosan) are effective and safe absorption enhancers to improve mucosal (nasal, peroral) delivery of hydrophylic macromolecules such as peptide and protein drugs and heparins. This absorption enhancing effect of chitosans is caused by opening of the intercellular tight junctions, thereby favouring the paracellular transport of macromolecular drugs. Chitosan nano- and microparticles are also suitable for controlled drug release. Association of vaccines to some of these particulate systems has shown to enhance the antigen uptake by mucosal lymphoid tissues, thereby inducing strong systemtic and mucosal immune responses against the antigens. The aspecific adjuvant activity of chitosans seems to be dependent on the degree of deacetylation and the type of formulation. From the studies reviewed it is concluded that chitosan and chitosan derivatives are promising polymeric excipients for mucosal drug and vaccine delivery.     

羧甲基壳聚糖银的合成及抑菌实验的研究

目的研究羧甲基壳聚糖银的合成方法及其对金黄色葡萄球菌、铜绿假单胞菌、大肠埃希菌、肺炎克雷伯菌和变形杆菌的抑菌作用。方法对壳聚糖经化学修饰后的衍生物进行红外吸收光谱分析。用稀释法和凹环法对烧伤常见的病原菌进行抑菌实验。结果修饰后的衍生物经红外图谱分析表明 ,壳聚糖已被氯乙酸所修饰。羧甲基壳聚糖银对浓度均为 10 4 CFU/ml的金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌的抑菌率分别为 88%、80 .2 %和 75 .3%。羧甲基壳聚糖银和AgNO3 对金黄色葡萄球菌、铜绿假单胞菌的最低抑菌浓度相同 ,对大肠埃希菌的最低抑菌浓度则前者低于后者。结论羧甲基壳聚糖银对烧伤感染常见致病菌有抑制作用 ,它可作为一种新型的预防、治疗烧伤感染的药物。     

Synthesis and anti-Helicobacter pylori activity of pyloricidin derivatives I. Structure-activity relationships on the terminal peptidic moiety

The novel natural antibiotics pyloricidin A, B and C possess potent and highly selective antibacterial activity against Helicobacter pylori. In order to investigate the structure activity relationships for the terminal peptidic moiety, a series of pyloricidin B and pyloricidin C derivatives, bearing various amino acids in the moiety, were prepared and evaluated for their anti-H. pylori activity. The derivatives bearing alpha-D-, beta- and gamma-amino acids or peptidemimetics showed drastically decreased activity. On the other hand, the derivatives with a-L-amino acids were found to maintain the activity. Among the derivatives prepared in this work, the allylglycine derivative 2s showed the most potent anti-H. pylori activity, with an MIC value of less than 0.006 microg/ml against H. pylori NCTC11637, which is 60-fold greater than the activity of the lead compound pyloricidin C.     

HPLC法测定银杏达莫氯化钠注射液的含量

目的建立HPLC法测定银杏达莫氯化钠注射液中银杏总黄酮和双嘧达莫含量的方法。方法色谱柱:Diamonsil C18柱(4.6 mm×200.0 mm,5μm),流动相:甲醇-乙腈-30 mmol.L-1磷酸二氢钠溶液(体积比为20∶20∶80),检测波长:360 nm,测定3种黄酮苷元(槲皮素、山柰酚和异鼠李素);流动相:质量分数为0.1%的磷酸二氢钠溶液-甲醇(体积比为30∶70),检测波长:290 nm,测定双嘧达莫。结果槲皮素在0.01~0.09 g.L-1(r=0.999 3)、双嘧达莫在0.005~0.035 g.L-1(r=0.999 4)内呈良好的线性关系,平均回收率分别为102.5%(RSD=1.6%)、100.6%(RSD=1.1%)。结论本法可用于银杏达莫氯化钠注射液的质量控制。     

Characterization of chitosan and its derivatives using asymmetrical flow field-flow-fractionation: a comparison with traditional methods

Chitosan and its derivatives are an important group of polymers used extensively in pharmaceutics. Thus, their physicochemical properties are of considerable interest and need to be characterized carefully. The most important feature to determine is their molecular weight and molecular weight distribution while the molecular weight of polymers plays an important role as pharmaceutical excipients. In this study, the feasibility of using asymmetrical flow field-flow-fractionation (AF4) connected online to a multi-angle light scattering (MALS) detector to measure the molecular weight of chitosans, trimethyl chitosans were studied and compared with the results from some traditional measurement methods. It was found that the influence of trimethyl chitosan synthesis process on the resulting molecular weight decrease depends on the initial molecular weight of chitosan. Significant molecular weight decrease was observed when chitosan molecular weight was larger than 100 kDa. In contrast, the influence was marginal when the molecular weight of chitosan was less than 50 kDa. The AF4-MALS was found to be a suitable method for the characterization of pure chitosans and trimethyl chitosans.     

HPLC/MS法测定人血浆中氯雷他定的浓度及人体生物等效性

目的建立测定人血浆中氯雷他定的LC/MS方法,并应用于药物制剂生物等效性研究。方法18名健康受试者单剂量口服氯雷他定20 mg后,血浆样品经液液萃取,通过液相色谱质谱联用法测定其质量浓度,并计算药动学参数。结果氯雷他定测定方法的线性为0.5~20.0μg.L-1,定量下限为0.5μg.L-1;参比制剂的主要药动学参数tmax为(0.94±0.21)h,ρmax为(16.41±2.83)μg.L-1,t1/2为(9.56±4.21)h,用梯形法计算,AUC0~t为(38.70±6.93)μg.h.L-1;受试制剂的主要药动学参数tmax为(0.94±0.21)h,ρmax为(16.45±2.42)μg.L-1,t1/2为(8.89±4.06)h,用梯形法计算,AUC0~t为(43.67±9.55)μg.h.L-1,以AUC0-t计算,受试制剂相对生物利用度为(113.4±19.0)%。结论该法适用于氯雷他定制剂的生物等效性评价。     

RPHPLC法测定盐酸曲美他嗪片的含量和有关物质

目的建立测定盐酸曲美他嗪片的含量和有关物质的RP HPLC法。方法色谱柱为Diamon-silTMC18柱(200 mm×4.6 mm,5μm),以甲醇0.03 mol.L-1磷酸二氢钾溶液(体积比为15∶85,pH=3.0)为流动相,流速为1.0 mL.min-1,检测波长为225 nm。结果盐酸曲美他嗪在5~50 mg.L-1内线性关系良好,r=0.999 9;平均回收率为100.4%,RSD为1.6%;检出限为25μg.L-1;有关物质各杂质峰与主峰之间的分离良好。结论该测定方法可作为盐酸曲美他嗪的含量测定方法,以控制其原料及制剂的质量。     

Anti-Helicobacter pylori agents. 5. 2-(Substituted guanidino)-4-arylthiazoles and aryloxazole analogues.

To extend the SAR study of guanidinothiazoles as a structurally novel class of anti-H. pylori agents, a series of 2-(substituted guanidino)-4-arylthiazoles and some 4-aryloxazole analogues were synthesized and evaluated for antimicrobial activity against H. pylori. Some of them were also subjected to H2 antagonist and gastric antisecretory assays. Several arylthiazoles were identified as potent anti-H. pylori agents, and of these, thienylthiazole derivative 44 exhibited the strongest activity (MIC = 0.0065 microg/mL) among the compounds obtained in our guanidinothiazole studies. Although 44 was void of H2 antagonist activity, pyridylthiazole derivative 39 had both potent anti-H. pylori and H2 antagonist activities. Thiazolylthiazole derivative 46 also showed potent anti-H. pylori activity, but the H2 antagonist activity was weak. On the other hand, no attractive activities were found in pyrimidyl, oxazolyl, isoxazolyl, imidazolyl, and oxadiazolylthiazole derivatives. The anti-H. pylori activity of the aryloxazole analogues was weaker than those of the corresponding arylthiazole derivatives, though they had potent H2 antagonist activity.