丝裂霉素C-聚氰基丙烯酸正丁酯磁性纳米球的制备方法及性质研究

 目的优化pH>6的乳化聚合法制备丝裂霉素C-聚氰基丙烯酸正丁酯磁性纳米球的处方工艺。方法通过正交实验设计考察乳化聚合法制备丝裂霉素C-聚氰基丙烯酸正丁酯磁性纳米球的工艺条件对纳米球粒径、包封率和载药量的影响,并考察了冷冻和温湿条件下对制剂稳定性的影响。结果优化的乳化聚合法制备的丝裂霉素C-聚氰基丙烯酸正丁酯磁性纳米球的数均粒径、包封率、载药量和饱和磁化强度分别为:(122.4±2.3)nm,(85.51±0.74)%,(8.61±0.04)%,(0.31±0.01)kA·m^-1。丝裂霉素C-聚氰基丙烯酸正丁酯磁性纳米球胶体溶液具有良好的抗寒和抗湿热性。结论在pH>6条件下乳化聚合制备丝裂霉素C-聚氰基丙烯酸正丁酯磁性纳米球具有粒径小、包封率和载药量高,质量稳定的特点。     

吸附法制备阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒的研究

 以胶粒动电位为指标，采用正交设计方法对聚氰基丙烯醚异丁酯毫微粒的制各条件进行了优化。根据阿克拉霉素Ａ在聚氰基丙烯酸异丁酯毫微粒上的吸附机理，以载药量与载药毫微粒动电位为指标，采用均匀设计方法优化了制备肝靶向阿克拉霉素Ａ聚氰基丙烯酸异丁酯毫微粒的工艺条件，在优化工艺条件下制得的载药毫檄粒粒径分布在４０～１２０ｎｍ范围，胶粒动电位为－１５．４７ｍＶ，载药量为４８．７６％，药物载带率为９８．８３％。粒径分布与动电位值均满足肝靶向要求，载物量与药物载带率均高于同类材料报道值。ＨＰＬＣ法证明了吸附法工艺制得的载药毫微粒中药物的稳定性。体外释药试验结果表明，载药毫微粒中药物的释放具缓择性。与一步法制得的载药毫微粒比较表明，阿克拉霉素Ａ聚氰基丙烯酸异丁酯毫微粒的载药机理主要是吸附。     

丝裂霉素C聚氰基丙烯酸正丁酯纳米粒细胞毒性的研究

 目的 研究丝裂霉素聚氰基丙烯酸正丁酯纳米粒及其载体对正常肝细胞株生长的毒性及其作用浓度与细胞抑制程度的关系。方法　采用MTT染色,乳酸脱氢酶释放量的测定,分析药物对正常肝细胞的毒性。结果　在低于28.56μg·mL^-1的浓度内聚氰基丙烯酸正丁酯纳米粒无细胞毒性,丝裂霉素聚氰基丙烯酸正丁酯纳米粒的细胞毒性低于丝裂霉素。结论　聚氰基丙烯酸正丁酯纳米粒可作为抗癌药物丝裂霉素的载体,载药后可降低丝裂霉素的细胞毒性。     

阿苯哒唑纳米球载药特征及物理稳定性考察

 目的考察阿苯哒唑氰基丙烯酸正丁酯纳米球的载药机制和物理稳定性。方法 等温吸附法考察氰基丙烯酸酯载体浓度、药物浓度和溶液pH等因素的载药特性;电导法考察阿苯哒唑纳米球的物理稳定性。同时,考察了以PVP,CMC-Na和HPMC作助悬剂对纳米球稳定性的影响。结果 阿苯哒唑纳米球以表面吸附载药为主,且药物的吸附遵循Langmuir方程。电导法加速试验结果显示,载药纳米球具有热力学不稳定性,加入4％的PVP作助悬剂可显著增加药物的物理稳定性。结论阿苯哒唑纳米球以表面吸附方式载药,有自发性凝聚沉降趋势,亲水性胶体可增加其物理稳定性。     

阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒动物体内分布研究

 分别对￣３Ｈ－阿克霉素Ａ聚氰基丙烯酸异丁酯毫微粒尾静脉ｉｖ给药和ｐｏ给药后小鼠体内分布特点及其与￣３Ｈ－阿克拉霉素Ａ水溶液的比较进行了研究。毫微粒制剂在小鼠各脏器中相对放射性强度以肝脏最高，尾静脉ｉｖ与ｐｏ给药分别达给予量的７１．２１％与５３．７６％，分别是￣３Ｈ－阿克拉霉素Ａ水溶液分布量的３．６２倍和３．９５倍。常位移植人肝癌模型裸小鼠尾静脉ｉｖ￣３Ｈ－阿克拉霉素Ａ聚氰基丙烯酸异丁酯毫微粒后各脏器分布特点与正常小鼠相似，肝癌组织中相对放射性强度达给予量的８．７９％，是￣３Ｈ－阿克拉霉素Ａ水溶液的９．３９倍。电镜观察发现载药毫微粒可进入肝脏实质细胞浆与肝脏枯否氏细胞浆中，也可进入肝脏瘤组织中。     

负载芍药苷-聚氰基丙烯酸正丁酯微球的制备及体外缓释性能研究

目的:运用改良的乳液聚合法制备芍药苷-聚氰基丙烯酸正丁酯微球,并测定载药微球的各项理化性质,绘制释放度曲线.方法:运用改良的乳液聚合法制备芍药苷-聚氰基丙烯酸正丁酯微球,在扫描电镜下观察其形状形态,利用公式计算其包封率及载药量.将微球溶解于PBS缓冲液及生理盐水后,运用分光光度法测定不同时间微球释放的药物浓度,绘制释放...     

庆大霉素毫微球的体内抗菌活性研究

 目的：观察庆大霉素与聚氰基丙烯酸正丁酯毫微球结合以后，其体内抗菌活性(特别是对细胞内感染)是否有所增加。方法：以鼠伤寒沙门杆菌感染的C57BL/6j小鼠为细胞内感染的动物模型，以小鼠存活率和器官组织中的活菌计数为指标，对庆大霉素聚氰基丙烯酸正丁酯毫微球的体内抗菌活性进行评价。结果：从存活率评价其治疗指数提高了10倍。肝、脾、肾中活菌计数最低可降至庆大霉素溶液组的1/426，1/141和1/30。结论：与庆大霉素溶液相比，庆大霉素毫微球明显提高了对伤寒沙门杆菌感染小鼠的治疗效果。     

β-榄香烯聚氰基丙烯酸正丁酯纳米粒的制备工艺研究

目的优化β-榄香烯聚氰基丙烯酸正丁酯纳米粒的制备工艺。方法以聚氰基丙烯酸正丁酯(polybutylcyanoacrylate,PBCA)为载药材料,采用界面缩聚法,以包封率为考察指标,通过单因素试验及正交试验设计优化制备工艺。结果该工艺条件下制得的纳米粒,形态规整,无黏连,大小较为均匀,平均粒径254 nm,平均包封率90.17%。结论本实验优化的制备工艺稳定可行。     

苦参碱毫微粒的制备及体外释药动力学研究

 目的制备肝靶向性苦参碱聚氰基丙烯酸正丁酯毫微粒并进行体外形态学及释药动力学研究。方法采用乳化聚合法制备,以毫微粒包封率为考察指标,均匀设计优化处方与工艺,高效液相色谱法测定含量,透析法考察其体外释药动力学特征。结果制得的毫微粒均匀圆整,算术平均粒径为(157.4±22.4)nm,包封率为(84.91±1.76)%,载药量为(16.98±0.35)%,体外释药具有双相动力学特征。结论该制备工艺稳定可行,可用于肝靶向苦参碱聚氰基丙烯酸正丁酯毫微粒的制备。     

阿苯达唑纳米球体外释药及大鼠在体吸收动力学相关性研究

 目的考察阿苯达唑纳米球在不同介质中体外释药；大鼠在体胃、肠吸收以及体内外相关性。方法以阿苯达唑混悬液为对照，分别考察了阿苯达唑聚氰基丙烯酸正丁酯纳米球(ABZ-PBCA-NP)，阿苯达唑-PVP-聚氰基丙烯酸纳米球(AZB-PVP-PBCA-NP)在0.1 mol·L^-1盐酸和pH为3.5，5.5和6.8的磷酸缓冲液中的累积释药百分数，并进行了大鼠在体胃和小肠吸收实验。结果阿苯达唑混悬液、ABZ-PBCA-NP和AZB-PVP-PBCA-NP在盐酸和磷酸缓冲液中的释药分别遵循Weibull函数，二项指数函数和Higuch方程。阿苯达唑混悬液和AZB-PVP-PBCA-NP 6 h内小肠内的吸收分别为21.40%和43.23％(P＜0.05)，胃中吸收随介质pH值增大而减小。结论纳米球具有缓释和长效作用，可显著地增大阿苯达唑溶解性和胃肠吸收，体外释药与在体吸收有良好相关性。     

微柱离心-HPLC测定胰岛素脂质体的包封率

目的使用微柱凝胶离心分离结合高效液相色谱法(HPLC)定量的方法,建立胰岛素脂质体包封率的测定方法。方法采用了改良的薄膜分散法来制备胰岛素脂质体。使用Sephadex G-50填充凝胶离心微柱,分别使用去离子水及磷酸缓冲液作为洗脱液,分离载药脂质体和游离胰岛素后,经HPLC测定胰岛素浓度并计算包封率。结果通过洗脱曲线确定了洗脱方式,上样体积为600μL,使用去离子水洗脱5次(每次600μL)可将载药脂质体完全洗脱,再使用pH 7.4磷酸盐缓冲液洗脱6次可将其中的游离药物完全洗脱。实现了完全分离载药脂质体与外水相游离药物,经HPLC测定并计算得出3批胰岛素脂质体的平均包封率为36.03%。结论对于亲水性多肽药物脂质体,微柱离心可以实现有效分离脂质体与游离药物的目的,结合HPLC测定其中胰岛素的含量,可以作为测定胰岛素脂质体包封率的有效方法。     

微柱离心-HPLC测定胰岛素脂质体的包封率

目的使用微柱凝胶离心分离结合高效液相色谱法(HPLC)定量的方法,建立胰岛素脂质体包封率的测定方法。方法采用了改良的薄膜分散法来制备胰岛素脂质体。使用Sephadex G-50填充凝胶离心微柱,分别使用去离子水及磷酸缓冲液作为洗脱液,分离载药脂质体和游离胰岛素后,经HPLC测定胰岛素浓度并计算包封率。结果通过洗脱曲线确定了洗脱方式,上样体积为600μL,使用去离子水洗脱5次(每次600μL)可将载药脂质体完全洗脱,再使用pH 7.4磷酸盐缓冲液洗脱6次可将其中的游离药物完全洗脱。实现了完全分离载药脂质体与外水相游离药物,经HPLC测定并计算得出3批胰岛素脂质体的平均包封率为36.03%。结论对于亲水性多肽药物脂质体,微柱离心可以实现有效分离脂质体与游离药物的目的,结合HPLC测定其中胰岛素的含量,可以作为测定胰岛素脂质体包封率的有效方法。     

壳聚糖修饰的载胰岛素聚乳酸-羟基乙酸共聚物纳米粒的生物黏附性及毒性评价

 目的 探讨壳聚糖修饰的聚乳酸-羟基乙酸共聚物（PLGA）纳米粒的生物黏附性，阐明其促吸收机制，并考察纳米粒的细胞毒性以评价其安全性。方法 以胰岛素为模型药物，采用FITC标记胰岛素，复乳法制备普通PLGA纳米粒，壳聚糖包裹制备生物黏附性PLGA纳米粒。粒度及表面电位分析仪测量纳米粒的粒径及Zeta 电位，超速离心法测定载药纳米粒的包封率，通过测定胃肠道中胰岛素的总量评价纳米粒的生物黏附性，并采用MTT法评价PLGA纳米粒的细胞毒作用。结果 纳米粒粒径均一，PLGA普通纳米粒及生物黏附性纳米粒的平均粒径分别为（124.7±11）和（136.6±13）nm，粒径差别不大，但壳聚糖包衣显著地增强了纳米粒的正电性，使得Zeta电位由负值（-1.67±0.05） mV逆转为正值（42.6±0.3）mV，并且提高了药物的包封率，由（46.67±1.82）%增至（52.73±2.96）%。生物黏附性纳米粒口服后胃肠道中胰岛素的总量显著高于普通纳米粒，3 h达到1.31倍。MTT法显示生物黏附性PLGA纳米粒及普通PLGA纳米粒在所考察的剂量范围内（≤25 mg·mL-1），均对细胞无特殊毒性。结论 壳聚糖修饰的PLGA生物黏附性纳米粒是蛋白多肽类药物口服给药的良好载体。     

胰岛素海藻酸钠纳米粒的制备及体内外评价

 目的制备具有较高药物包封率的胰岛素海藻酸钠纳米粒(insulin-loaded sodium alginate nanoparticles,INS-SA-NP),考察其对糖尿病模型大鼠的降血糖作用。方法以胰岛素为模型药物,采用溶剂扩散法制备胰岛素海藻酸钠纳米粒,考察制备工艺对纳米粒粒径和电位的影响,测定药物包封率。采用糖尿病模型大鼠经呼吸道插入给药,评价胰岛素海藻酸钠纳米粒的降血糖作用。结果胰岛素海藻酸钠纳米粒的平均粒径416.4 nm,Zeta电位值(-92.6±1.8)mV,平均包封率(89.72±3.90)%;该纳米粒经呼吸道插入给药后,以皮下注射胰岛素溶液1 u·kg^-1为对照,其相对生物利用度达到61.64%,维持降血糖作用的时间明显延长。结论以溶剂扩散法制备得到的胰岛素海藻酸钠纳米粒,具有较高的药物包封率,该纳米粒经大鼠呼吸道插入给药后,降血糖作用显著延长。     

Box-Behnken效应面法优化大黄素/小檗碱-壳聚糖双载药纳米粒的处方工艺研究

目的优化大黄素(Emo)与小檗碱(Ber)壳聚糖双载药纳米粒的制备工艺和处方,并考察其稳定性及溶出度。方法以壳聚糖(CS)为载体,三聚磷酸钠(TPP)为交联剂,采用离子交联法包载大黄素/羟丙基-β-环糊精(HP-β-CD)和小檗碱,得到载药纳米粒(Emo/HP-β-CD-Ber-CS NPs),以粒径和多分散指数(PDI)为自变量,运用总评归一值(OD)法进行数据处理,采用Box-Behnken效应面法优化处方并进行验证。最后对纳米粒的最佳冻干条件进行筛选,考察保护剂种类和用量。并对制剂进行表征和溶出度考察。结果优化得到的最佳制备工艺为壳聚糖与TPP质量比为3∶1,小檗碱与载体质量比为0.166∶1,Emo/HP-β-CD与载体质量比为0.2∶1。测得Emo/HP-β-CD-Ber-CS NPs的平均粒径为(178.0±2.0)nm,PDI为0.187±0.006,平均OD值为0.9536,实测值与预测值接近。大黄素和小檗碱的载药量分别为0.34%和0.95%。稳定性考察结果表明,纳米粒胶体溶液在9 d内以4℃储存物理性质稳定,以6%葡萄糖为保护剂制得的冻干制剂效果较好,复溶迅速,再分散后的平均粒径为(161.8±4.8)nm,PDI为0.263±0.047。体外释放研究表明载药纳米粒冻干粉溶解度和溶出度显著提高。结论Box-Behnken效应面法所建立的模型能较好的用于Emo/HP-β-CD-Ber-CS NPs制剂的处方优化,精度高,预测效果较好,且Emo/HP-β-CD-Ber-CS NPs制备工艺稳定可行。     

Abelmoschus moschatus (Malvaceae), an aromatic plant,suitable for medical or food uses to improve insulin sensitivity

Abelmoschus moschatus (Malvaceae) is an aromatic and medicinal plant, distributed in many parts of Asia, including south Taiwan. The present study was undertaken to clarify whether the herb is effective in improving insulin resistance. Insulin resistance in rats was induced by a diet containing 60% fructose for 6 weeks. The degree of insulin resistance was measured by homeostasis model assessment of basal insulin resistance (HOMA‐IR). Insulin sensitivity was calculated using the composite whole body insulin sensitivity index (ISIcomp) during the oral glucose tolerance test. Insulin receptor‐related signaling mediators in soleus muscles of rats were evaluated by immunoprecipitation or immunoblotting. The extract of A. moschatus had a higher level of polyphenolic flavonoids. A. moschatus extract (200 mg/kg per day) displayed the characteristics of rosiglitazone (4 mg/kg per day) in reducing the higher HOMA‐IR index as well as elevating ISIcomp in fructose chow‐fed rats after a 2‐week treatment. Treatment with moschatus extract for 2 weeks increased post‐receptor insulin signaling mediated by enhancements in insulin receptor substrate‐1‐associated phosphatidylinositol 3‐kinase step and glucose transporter subtype 4 translocation in insulin‐resistant soleus muscles. A. moschatus is therefore proposed as potentially useful adjuvant therapy for patients with insulin resistance and/or the subjects wishing to increase insulin sensitivity. Copyright © 2009 John Wiley & Sons, Ltd.     

Anti-diabetic effects of linarin from Chrysanthemi Indici Flos via AMPK activation

Objective: The purpose of this study is to investigate the anti-diabetic effects of linarin, a flavonoid extracted from Chrysanthemi Indici Flos (CIF), and its potential mechanisms. Methods: The effects of linarin on cell viability and glucose consumption in HepG2 cells were measured. Meanwhile, monosodium glutamate (MSG) mouse model was constructed to monitor the changes of insulin tolerance, glucose tolerance, triglyceride and cholesterol. The protein expression levels of p-AMPK, p-ACC, PEPCK and p-GS were detected by Western blot. Results: Linarin could increase the relative glucose consumption of HepG2 cells, improve insulin tolerance and glucose tolerance, and decrease the levels of triglyceride and cholesterol of MSG mice. Simultaneously, the expression levels of p-AMPK and p-ACC in HepG2 cells and the liver tissue of MSG mice were increased, while the expression levels of PEPCK and p-GS were decreased after treatment with linarin. Conclusion: Insulin resistance could be ameliorated by linarin in type 2 diabetes, and its mechanism may be related to AMPK signaling pathway.     

牛心柿叶多糖对链脲佐菌素致糖尿病小鼠的影响

目的:研究牛心柿叶多糖对链脲佐菌素(STZ)致糖尿病小鼠的影响.方法:SPF级昆明种小鼠50只腹腔注射STZ 150 mg·kg-1建立糖尿病小鼠模型.检测空腹血糖(FBG)指数确定成模后,随机分成模型组、二甲双胍阳性组及牛心柿叶多糖低、中、高剂量组,每组10只.ig给与牛心柿叶多糖0.3,0.6,1.2 g·kg-1,阳性组给予二甲双胍0.32 g·kg-1,正常对照组及模型组给予等量生理盐水,连续灌胃15 d.在第15天给药前禁食12h,给药1h后取血,葡萄糖氧化酶法测定空腹血糖(FBG),放射免疫测定法测定胰岛素指标的空腹胰岛素(FNS)、胰岛素敏感指数(ISI)及胰岛素抵抗(IR),生化法测定甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)等指标.结果:与模型组比较,给药组有效缓解糖尿病小鼠病情,牛心柿叶多糖明显降低糖尿病小鼠的血糖和血脂水平(P ＜0.05或P＜0.01),并有效提高胰岛素水平(P ＜0.05或P＜0.01),改善胰岛胰岛素抵抗能力.结论:牛心柿叶多糖具有有效降血糖和降血脂作用,机制可能与其能恢复小鼠胰岛功能以及增强机体抗氧化能力有关.     

The effect of medicinal plants of Islamabad and Murree region of Pakistan on insulin secretion from INS-1 cells

In vitro testing of the extracts of medicinal plants collected from Islamabad and the Murree region on insulin secretagogue activity was carried out. Dried ethanol extracts of all plants (ZH1-ZH19) were dissolved in ethanol and DMSO, and tested at various concentrations (between 1 and 40 microg/mL) for insulin release from INS-1 cells in the presence of 5.5 mM glucose. Glibenclamide was used as a control. Promising insulin secretagogue activity in various plant extracts at 1, 10, 20 and 40 microg/mL was found, while in some cases a decrease in insulin secretion was also observed. Artemisia roxburghiana, Salvia coccinia and Monstera deliciosa showed insulin secretagogue activity at 1 microg/mL (p < 0.05) while Abies pindrow, Centaurea iberica and Euphorbia helioscopia were active at 10 microg/mL (p < 0.05). Extracts of Bauhinia variegata and Bergenia himalacia showed effects at 20 microg/mL (p < 0.05), and Taraxacum officinale and Viburnum foetens at 40 microg/mL (p < 0.05). Insulin secretagogue activity could not be detected in the extracts of Adhatoda vasica, Cassia fistula, Chrysanthemum leucanthemum, Morus alba, Plectranthus rugosus, Peganum harmala and Olea ferruginea. The results suggest that medicinal plants of Islamabad and the Murree region of Pakistan may be potential natural resources for antidiabetic compounds.     

Effect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice

Insulin resistance, which precedes type 2 diabetes mellitus (T2DM), is a widespread pathology associated with the metabolic syndrome, myocardial ischemia, and hypertension. Finding an adequate treatment for this pathology is an important goal in medicine. The purpose of the present research was to investigate the effect of an extract from Aloe vera gel containing a high concentration of polyphenols on experimentally induced insulin resistance in mice. A polyphenol-rich Aloe vera extract (350 mg/kg) with known concentrations of aloin (181.7 mg/g) and aloe-emodin (3.6 mg/g) was administered orally for a period of 4 weeks to insulin resistant ICR mice. Pioglitazone (50 mg/kg) and bi-distilled water were used as positive and negative controls respectively. Body weight, food intake, and plasma concentrations of insulin and glucose were measured and insulin tolerance tests were performed. The insulin resistance value was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. Results showed that the polyphenol-rich extract from Aloe vera was able to decrease significantly both body weight (p < 0.008) and blood glucose levels (p < 0.005) and to protect animals against unfavorable results on HOMA-IR, which was observed in the negative control group. The highest glucose levels during the insulin tolerance curve test were in the negative control group when compared to the Aloe vera extract and pioglitazone treated mice (p < 0.05). In conclusion, Aloe vera gel could be effective for the control of insulin resistance.