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。     

分子参数对5-氟尿嘧啶-N-琥珀酰壳聚糖纳米粒理化性质的影响

目的：考察5-氟尿嘧啶-N-琥珀酰壳聚糖纳米粒（5-FU-Suc-Chi/NPs）理化性质影响因素。方法：采用乳化溶剂挥发法制备5-FU-Suc-Chi/NPs并考察其理化性质的影响因素。结果：5-FU-Suc-Chi/NPs的粒径、Zeta电位、包封率及载药量的大小与N-琥珀酰壳聚糖的取代度（DS）和分子量（Mw）有关。结论：N-琥珀酰壳聚糖的分子参数是影响5-FU-Suc-Chi/NPs理化性质的重要因素。     

卡维地洛pH敏感性N-琥珀酰壳聚糖-海藻酸钙水凝胶的制备工艺优选

目的:优选卡维地洛pH敏感性N-琥珀酰壳聚糖-海藻酸钙水凝胶的最佳制备工艺,并考察其pH敏感性。方法:以包封率和载药量为考察指标,采用L9(34)正交试验优选其制备工艺。评价水凝胶在不同pH值溶液中的pH敏感性。结果:优选的最佳工艺为2%(w/v)N-琥珀酰壳聚糖,2%(w/v)海藻酸钠,2%(w/v)氯化钙,药物与海藻酸钠的质量比为1∶4(g/g)。水凝胶在pH1.5的溶液中几乎不溶胀,在pH6.8的溶液中溶胀度最大。结论:优选的制备工艺合理可行,制备的水凝胶具有明显的pH敏感性及缓释效果。     

硝苯地平智能水凝胶的质量标准研究

<正>硝苯地平智能水凝胶是以硝苯地平为主药,N-琥珀酰壳聚糖、海藻酸钠为主要高分子载体材料,采用离子胶凝化法制备的pH敏感的智能药物。本文建立的高效液相色谱法     

口服双氯芬酸钠pH敏感性水凝胶球研究

目的：以N-琥珀酰壳聚糖、海藻酸钠为载体,制备口服双氯芬酸钠pH敏感性水凝胶小球,并考察该水凝胶小球在不同pH环境中的释放行为。方法：通过正交试验优选口服双氯芬酸钠pH敏感性水凝胶小球最佳制备工艺。采用红外光谱和电子显微镜扫描对其进行结构表征,并考察该水凝胶小球在体外不同pH环境、人工胃液及人工肠液中的释放行为,揭示其在体外不同环境中的pH敏感性释放机制。结果：该水凝胶小球最佳处方组成为：N-琥珀酰壳聚糖浓度为1％(w/v),海藻酸钠浓度为1％(w/v),氯化钙浓度为1.5％(w/v),药物与海藻酸钠质量比为3∶5(g/g);口服双氯芬酸钠pH敏感性水凝胶小球具有明显的pH敏感性,在人工胃液中3 h的累积释放度小于22%,在人工肠液中11 h的累积释放度可达98%。结论：口服双氯芬酸钠pH敏感性水凝胶小球可望成为具有时辰药理学特性的pH敏感性肠道释药系统。     

响应曲面法优化NSC/APT凝胶小球的制备工艺及其释药特性考察

目的 探索N-琥珀酰壳聚糖/凹凸棒黏土（NSC/APT）释药凝胶小球的制备工艺,考察其释药特性.方法 利用响应曲面法优化了制备工艺,采用安全无毒的氯化钙进行交联.结果 与结论通过响应曲面法优化的最佳工艺与模型拟合很好;所得凝胶小球的溶胀率和累积药物释放实验结果表明复合凝胶小球具有pH敏感性,在pH为1.2时基本不溶胀,3h药物仅释放0.66%;pH为5.8时溶胀率增加,3h药物累积释放达到62.55%;pH为6.8时溶胀率最大,药物释放速度最快,3h达到94.51%;但当pH增加至8.0时,溶胀率减小,3h释放了76.05%.琥珀酰壳聚糖的羧基在药物释放中起着关键作用.     

N-琥珀酰壳聚糖纳米粒肿瘤靶向性及抗肿瘤活性评价

目的评价N-琥珀酰壳聚糖纳米粒（Suc-Chi/NPs）肿瘤靶向性,考察5-氟尿嘧啶-N-琥珀酰壳聚糖纳米粒（5-FU-Suc-Chi/NPs）抗肿瘤活性。方法建立异硫氰基荧光素（FITC）-Suc-Chi/NPs的体内荧光分析方法,检测Suc-Chi/NPs在Sarcoma 180-荷瘤小鼠体内组织分布数量。采用荧光显微镜观察FICT-Suc-Chi/NPs在组织切片中蓄积量,评价FICT-Suc-Chi/NPs肿瘤靶向性;以Suc-Chi/NPs、5-FU注射液为对照,考察5-FU-Suc-Chi/NPs在Sarcoma 180-荷瘤小鼠体内的瘤体积抑制率及对荷瘤小鼠体重的影响,评价制剂的疗效及不良反应。结果 FICT-Suc-Chi/NPs能够长时间的滞留在血液中,在各组织及血浆中分布的数量次序依次为肾〉肿瘤〉血液〉肝〉脾〉肺。5-FU-Suc-Chi/NPs与5-FU注射液相比较,能够更有效地抑制Sarcoma 180肿瘤的生长,而且组织毒性较温和。结论研究表明N-琥珀酰壳聚糖纳米粒具有长循环特性,能够实现实体肿瘤靶向传递;以N-琥珀酰壳聚糖为载体包载抗肿瘤模型药纳米粒具有较高抗肿瘤活性及较低的毒性。     

N-正辛基-N''''-琥珀酰基壳聚糖的制备及其对4种肿瘤细胞的亲和性

目的以不同分子质量的壳聚糖为原料合成系列的N-正辛基-N'-琥珀酰基壳聚糖,考察其与肿瘤细胞的亲和性,为其作为抗肿瘤药物的靶向载体提供依据.方法用异硫氰酸荧光素(FITC)对N-正辛基-N'-琥珀酰基壳聚糖进行标记,再分别与人肝癌细胞(HepG2)、人白血病细胞(K562)、人非小细胞肺癌细胞(A549)及人胃癌细胞(BGC)共培养,通过流式细胞仪及酶联免疫检测仪测定N-正辛基-N'-琥珀酰基壳聚糖对肿瘤细胞的亲和性及抑制力.结果N-正辛基-N'-琥珀酰基壳聚糖对4种肿瘤细胞亲和性明显强于空白细胞株(P＜0.01),并具有一定的肿瘤抑制作用.结论N-正辛基-N'-琥珀酰基壳聚糖有望作为抗肿瘤药物的靶向载体.     

N-琥珀酰壳聚糖纳米粒的制备及体外评价

目的制备N-琥珀酰壳聚糖纳米粒并对其进行体外评价。方法采用乳化溶剂挥发法制备N-琥珀酰壳聚糖纳米粒;以包封率、载药量及粒径为指标,采用正交设计法对处方进行优化;考察其理化特征及体外释药行为。结果纳米粒包封率及载药量分别为62.36%和18.98%,平均粒径及zeta电位分别为(206.6±64.7)nm和(-27.2±0.2)mV;1 h药物释放达到45%,随后药物的释药行为是一个缓释过程。结论作者采用乳化溶剂挥发法成功制得N-琥珀酰壳聚糖纳米粒。该方法制得纳米粒包封率较高,制备工艺简单。     

N-正辛基-N′-琥珀酰基壳聚糖的制备及其对4种肿瘤细胞的亲和性

目的:以不同分子质量的壳聚糖为原料合成系列的N-正辛基-N′-琥珀酰基壳聚糖,考察其与肿瘤细胞的亲和性,为其作为抗肿瘤药物的靶向载体提供依据。方法:用异硫氰酸荧光素(FITC)对N-正辛基-N′-琥珀酰基壳聚糖进行标记,再分别与人肝癌细胞(HepG2)、人白血病细胞(K562)、人非小细胞肺癌细胞(A549)及人胃癌细胞(BGC)共培养,通过流式细胞仪及酶联免疫检测仪测定N-正辛基-N′-琥珀酰基壳聚糖对肿瘤细胞的亲和性及抑制力。结果:N-正辛基-N′-琥珀酰基壳聚糖对4种肿瘤细胞亲和性明显强于空白细胞株(P＜0．01),并具有一定的肿瘤抑制作用。结论:N-正辛基-N′-琥珀酰基壳聚糖有望作为抗肿瘤药物的靶向载体。     

Challenges in Determining Intrinsic Viscosity Under Low Ionic Strength Solution Conditions

Purpose

To determine the intrinsic viscosity of several monoclonal antibodies (mAbs) under varying pH and ionic strength solution conditions.

Methods

An online viscosity detector attached to HPLC (Viscotek®) was used to determine the intrinsic viscosity of mAbs. The Ross and Minton equation was used for viscosity prediction at high protein concentrations. Bulk viscosity was determined by a Cambridge viscometer.

Results

At 15 mM ionic strength, intrinsic viscosity of the mAbs determined by the single-point approach varied from 5.6 to 6.4 mL/g with changes in pH. High ionic strength did not significantly alter intrinsic viscosity, while a significant increase (up to 24.0 mL/g) was observed near zero mM. No difference in bulk viscosity of mAb3 was observed around pH 6 as a function of ionic strength. Data analysis revealed that near zero mM ionic strength limitations of the single-point technique result in erroneously high intrinsic viscosity.

Conclusions

Intrinsic viscosity is a valuable tool that can be used to model baseline viscosity at higher protein concentrations. However, it is not predictive of solution non-ideality at higher protein concentrations. Furthermore, breakdown of numerous assumptions limits the applicability of experimental techniques near zero mM ionic strength conditions. For molecules and conditions studied, the single-point approach produced reliable intrinsic viscosity results at 15 mM. However, this approach must be used with caution near zero mM ionic strength. Data analysis can be used to reveal whether determined intrinsic viscosity is reliable or erroneously high.

     

两种新型增粘剂在环丙沙星滴眼剂中的应用

目的：寻求一种能延长滴眼剂在眼球周围的附着时间、生物兼容性和稳定性好、价廉的新型增粘剂。方法：采用紫外分光光度法测定了在加速试验条件下环丙沙星在几丁糖和透明质酸钠溶液中的稳定性,用药液小滴与固体浸润角和毛细管方法分别测定了几丁糖和透明质酸钠增稠后,环丙沙星滴眼液的表面张力和粘度,并测定了增稠后的滴眼液对兔眼的刺激性。结果：环丙沙星的含量在加速试验中无明显变化表面张力接近,粘度增加,两种增粘剂加入后     

长春西汀海藻酸钠骨架片体外释药影响因素研究

目的以海藻酸钠为骨架材料 ,制备长春西汀控释骨架片 ,对影响其体外释放的多种因素进行了考察。方法以海藻酸钠为亲水骨架材料 ,粉末直接压片制备长春西汀控释片 ,采用《中华人民共和国药典》2 0 0 0年版二部收载的溶出度测定方法Ⅱ法 (桨法 ) ,测定药物在不同条件下的体外释放度 ,考察海藻酸钠用量及黏度 ,枸橼酸用量 ,释放介质离子强度和pH值对药物体外释放行为的影响。结果与结论海藻酸钠用量及黏度 ,枸橼酸用量 ,释放介质离子强度和pH值均对药物体外释放行为有显著影响。值得注意的是 ,通过调节处方中枸橼酸用量可以使释药行为达零级 ,这为制备长春西汀控释片提供指导 ,有进一步开发的价值。     

透明质酸的热降解研究

采用流通蒸汽法对透明质酸进行热降解研究。结果表明，随着热处理时间的延长，透明质酸分子量（Mr）降低，特性黏度和Mr降低速率变小，而葡糖醛酸含量基本不变。回归分析表明，Mr与热处理时间t符合对数方程Mr=-47．18Int＋154．64。说明热降解是制备特定Mr范围透明质酸的简便方法。     

Poly(N-isopropylacrylamide) copolymers for constant temperature controlled drug delivery

To assess the prolongation of epidural bupivacaine by hyaluronic acid viscous formulations we designed a cross-over study in rabbits. Different doses of bupivacaine (3 or 6 mg) either as a solution (bupivacaine hydrochloride), or as viscous formulations with hyaluronic acid (bupivacaine base and bupivacaine hydrochloride) were administered in a rabbit model of epidural anesthesia. In the first part of the study, in vitro release characteristics were determined. Then pharmacodynamic effects and pharmacokinetic profiles of each bupivacaine formulation were studied. The rank order release rate of bupivacaine in vitro was always hydrochloride solution > viscous physical mixture of bupivacaine with hyaluronic acid > viscous ionic complex of bupivacaine base with hyaluronic acid. Onset time of epidural anesthesia was similar whatever the formulation of bupivacaine used. We did not find any blockade prolongation when 3mg bupivacaine was administered, but significant blockade prolongations were observed with viscous formulations incorporating 6 mg bupivacaine. The observed reduction in the absorption rate of bupivacaine into the systemic circulation for both viscous hyaluronic formulations after 6 mg of bupivacaine may explain the prolongation of spinal effects. Drug release and duration of action were found to be viscosity controlled as linear relationships were found between pharmacodynamic effects and viscosity. Our results were in accordance with those reported with bupivacaine-cyclodextrin complex, another formulation with a molecular dispersion of the drug, resulting in a moderate prolongation of action.     

透明质酸滴眼剂制备及其临床初步应用

选用新鲜正常人脐带为原料,经蛋白水解酶酶解消化,氯代十六烷基吡啶和乙醇分次沉淀,获透明质酸粗品,精制成钠盐成品。其核酸含量为2.67%,蛋白质含量为0.50%,锥板粘度为1.87mPa·?毛细管粘度为1.79mPa·s,pH为6.9。紫外和红外吸收图谱与文献报道基本一致。理化分析结果及质量已达眼科外用要求。将成品配制成滴眼剂,经动物实验证明,无致炎及毒副作用。作为辅助治疗用药经临床试用,对干眼症等疾病治疗,收到了较好效果。     

甘草酸水溶液的凝胶化特性

目的：明确甘草酸水溶液发生凝胶化的影响因素及凝胶特性。方法：考察浓度、温度、酸度及有机溶剂对甘草酸水溶液凝胶行为的影响,并分析所得水凝胶的持水性,表征水凝胶冻干粉的形貌特征和红外图谱。结果：当甘草酸水溶液浓度达20 mg·mL^-1时经放置后可形成稳定性良好的水凝胶,该凝胶黏度随温度升高而逐渐降低;甘草酸水凝胶的形成还受到pH值及有机溶剂等的影响;所得凝胶的持水性良好,其冻干粉的红外光谱与原料基本一致。结论：甘草酸水溶液可在一定条件下形成具有较高强度和黏度的水凝胶,有望作为多功能药物载体用于新型递药系统。     

Mechanistic study of electroosmotic transport across hydrated nail plates: effects of pH and ionic strength

The objective of this study was to investigate the effects of pH and ionic strength on electroosmotic transport in transungual iontophoresis. Transungual iontophoretic transport of model neutral permeants mannitol (MA) and urea (UR) across fully hydrated human nail plates in phosphate-buffered saline of different pH and ionic strengths were investigated in vitro. Two protocols were involved in the transport experiments with each protocol divided into stages including passive and iontophoresis transport at 0.1 and/or 0.3 mA. Nail plate electrical resistance and water uptake of nail clippings were measured at various pH and ionic strengths. In the pH study, electroosmosis enhanced the anodal transport of MA at pH 9 and cathodal transport at pH 3. The Peclet numbers of MA were more than two times higher than those of UR under these conditions. No significant electroosmosis enhancement was observed for MA and UR at pH 5. In the ionic strength study, a decrease in solution ionic strength from 0.7 to 0.04 M enhanced electroosmotic transport. Nail electrical resistance increased with decreasing the ionic strength of the equilibrating solution, but reached a plateau when the ionic strength was less than approximately 0.07 M. Solution pH and ionic strength had no significant effect on nail hydration. Under the studied pH and ionic strength conditions, the effects of electroosmosis were small compared to the direct-field effects in transungual iontophoretic transport of small to moderate size permeants.     

透明质酸酶催化透明质酸水解的最适反应条件

目的确定透明质酸酶(HAase)催化透明质酸(HA)水解的最适条件。方法HAase不同条件下催化HA水解,反应结束后利用高效凝胶渗透色谱(HPGPC)法测量反应产物的相对分子质量及其分布系数。结果HAase催化HA水解受温度、pH值、酶浓度、底物浓度、反应时间等因素的影响。结论HAase催化HA水解的最适反应条件是底物浓度为10 g/L,酶浓度为150 000 U/L,pH为5.0,反应温度为50℃。     

羧甲基壳聚糖金属配合物的研制

应用水溶性的羟甲基壳聚糖与Ca^2 、Fe^2 、Zn^2 进行络合制备金属配合物,探讨反应时间、温度、羧甲基取代度、溶液离子强度、pH等反应条件对络合的影响,考察金属配合物的性质。结果表明：络合反应的最佳pH值为5－7;室温下反应10min络合量趋于饱和;羧甲基壳聚糖对各金属离子络合能力随羧甲基取代度的增大而增强,随着体系的离子强度增大而减弱。