褪黑素对大鼠电针镇痛效应的影响

本实验以 5 0℃热水刺激引起的大鼠甩尾反应为痛反应指标 ,观察腹腔注射 (i p )不同剂量褪黑素 (MEL) 3 0、60、1 2 0mg/kg的镇痛效应 ,及MEL 60mg/kg对电针镇痛效应的影响。结果显示 ,i p MEL 3 0mg/kg对大鼠甩尾潜伏期无影响 ;i p MEL 60、1 2 0mg/kg均能显著延长大鼠甩尾潜伏期 ,作用随着剂量增大而增强 ;i p MEL 60mg/kg 3 0分钟后给予电针刺激 3 0分钟 ,大鼠甩尾潜伏期显著长于单纯给药组和单纯电针组 ,提示褪黑素具有镇痛作用 ,并能加强电针镇痛效应。     

艾灸对实验性类风湿性关节炎大鼠海马GR、MEL1B表达影响的研究

目的:探索艾灸治疗实验性类风湿性关节炎(RA)大鼠海马中枢的功能机制。方法:将SD大鼠随机分为空白对照组、RA模型组、艾灸组,用弗氏完全佐剂制造实验性RA病理模型,艾灸"肾俞"、"足三里"穴治疗,用免疫组化法测定大鼠海马糖皮质激素受体(GR)表达,用原位杂交法检测海马褪黑激素受体1B(MEL1B)表达。结果:模型组与空白组比较,GR表达有增高趋势(P>0.05),艾灸组显著低于模型组(P<0.01)。模型组与空白组比较,MEL1B光密度值显著增高(P<0.01),艾灸组明显低于模型组(P<0.05)。结论:艾灸对实验性RA海马中枢有良性调整作用,海马GR、MEL1B在艾灸治疗实验性RA大鼠抗炎效应中具有重要作用。     

干旱和温度胁迫对广州相思子种子萌发的影响

目的研究低温和干旱胁迫对药用植物广州相思子(Abrus cantoniensis)种子萌发和幼苗生长的影响。方法以聚乙二醇(PEG6000)模拟干旱,测定发芽率、发芽势、发芽指数等指标。结果低温(15℃、20℃)和干旱(PEG浓度5%～30%)相互作用时,发芽率随PEG浓度的增加而逐渐降低。较高温(25℃、30℃、35℃)和干旱(PEG浓度5%～30%)相互作用时,发芽率随PEG浓度的增加呈现先升高后降低的趋势,5%和10%的PEG可显著提高广州相思子种子发芽率。结论低温条件下广州相思子种子抗旱能力差,适宜温度条件下种子具有较强的抗旱能力。     

多指标正交试验优化儿黄缓释双层栓处方

目的优化儿黄缓释双层栓的处方。方法选择聚乙二醇(PEG)400、PEG4000、羟丙基甲基纤维素(HPMC)的用量为影响因素,采用L9(34)正交试验,以3个不同时间点的累积释放度作为指标,进行综合评分,分别对儿黄缓释双层栓的内层和外层进行优化设计。结果优选出内层的最优处方为HPMC∶PEG4000∶PEG400=1.5∶10∶4,外层的最优处方为HPMC∶PEG4000∶PEG400=0.5∶10∶4。结论根据本试验优化处方制备的儿黄缓释双层栓成型性好,并具有良好的缓释作用,对中药栓剂的研究开发具有一定的参考价值。     

温度和干旱胁迫对3种大黄种子萌发和幼苗生长的影响

目的 研究不同温度和聚乙二醇(PEG)模拟干旱胁迫对大黄种子萌发的影响,探讨大黄种子萌发的最适温度和对干旱胁迫的耐性。方法 用6个温度(10、15、20、25、30、35℃)和6个聚乙二醇(PEG-6000,以下简称PEG)浓度(0、5%、10%、15%、20%、25%)模拟温度胁迫与干旱胁迫对大黄种子进行处理,置人工培养箱培育,借助SPSS24.0单因素方差分析法对其发芽势、发芽率、胚根、胚轴和子叶等指标统计分析。结果 温度与干旱胁迫对3种大黄种子萌发及幼苗生长有显著影响(P<0.05);同一温度下,3种大黄的种子萌发指标随PEG浓度的升高而降低,掌叶大黄和唐古特大黄幼苗各指标亦是随PEG浓度的升高而降低,而药用大黄幼苗各指标随着PEG浓度的升高先增加后减小,在低浓度PEG(5%)达到最大,25%PEG重度干旱时严重抑制掌叶大黄和唐古特大黄萌发(P<0.05),完全抑制药用大黄萌发;20℃或25℃下,各PEG浓度处理的3种大黄种子萌发及幼苗生长指标均达到最大值;在低于20℃或者高于25℃时,各PEG浓度下的指标呈下降趋势,35℃高温下种子萌发和幼苗生长指标随着PEG浓度的...     

不同聚乙二醇相对分子质量对包载羟基喜树碱的PEG-PHDCA纳米囊泡体外释放和体内药动学行为的影响

 目的探讨不同聚乙二醇(PEG)相对分子质量对包载羟基喜树碱的聚乙二醇化聚十六烷基氰基丙烯酸酯(PEG-PHDCA)纳米囊泡体内外行为的影响。方法采用薄膜分散-水化超声法制备了羟基喜树碱的PEG-PHDCA纳米囊泡,在研究该纳米囊泡的形态、粒径、载药量、包封率、冷冻干燥工艺后对其体外释药特征及体内药动学参数进行测定。结果纳米囊泡的载药量、体外释药、体内药动学行为等与不同PEG相对分子质量有关。随着PEG相对分子质量从2000上升到10000,囊泡的载药量从3.04%下降到1.99%;体外释药符合Higuchi方程,随PEG相对分子质量的上升,囊泡的释药速率加快;在SD大鼠的药动学实验中,血药浓度-时间曲线符合二室开放药动学模型,PEG相对分子质量为2000,5000,10000的PEG-PHDCA纳米囊泡可分别将HCPT的血浆半衰期从0.72h延长到7.17,11.46,6.39h(P<0.001),AUC分别为HCPF的8.40,24.50,6.24倍(P<0.001)。结论在本实验范围内,PEG相对分子质量为5000的PEG-PHDCA载药纳米囊泡体外具有一定的缓释作用,体内具有最佳的长循环效果。     

聚乙二醇化葛根素对大鼠心肌缺血再灌注损伤的保护作用

目的 探讨聚乙二醇(PEG)化葛根素对大鼠心肌缺血再灌注损伤(MIRI)的保护作用.方法 将SD大鼠随机分为6组(每组10只):假手术组,MIRI模型组,葛根素注射剂(20 mg/kg)对照组,PEG化葛根素低、中、高剂量(244、488、976 mg/kg)组.阻断大鼠升主动脉造成心肌缺血30 min,再灌注120 min,造成大鼠MIRI模型,在结扎后5 min各给药组尾iv给药.心电图监测心律失常情况,再灌注结束后腹主动脉采血,测定血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、天冬氨酸转氨酶(AST)和丙二醛(MDA)水平,并测量心肌梗死面积.结果 葛根素注射剂和PEG化葛根素均具有抗心律失常,降低血清中CK、LDH、AST和MDA水平的作用,减少心肌梗死面积;其中PEG化葛根素中、高剂量组的药效明显强于葛根素注射剂组.结论 PEG化葛根素对大鼠MIRI引起的损伤具有保护作用.     

聚乙二醇修饰的聚酰胺-胺-甲氨蝶呤分子复合物的制备及体外释药研究

 目的分别制备了聚乙二醇(PEG)修饰的第四代(G4)和第五代(G5)聚酰胺-胺(PAMAM)树枝状大分子-甲氨蝶呤(MTX)复合物,考察其体外释药特性。方法通过酰胺键将功能化PEG与PAMAM表面氨基连接,考察PEG化PAMAM的溶血毒性;制备PAMAM-PEG/MTX复合物,测定最大复合量;考察复合物在不同缓冲溶液及血浆中的体外释药行为及不同储存条件下的稳定性。结果通过PEG化修饰,每分子G4 PAMAM分别连接了11,21和29个PEG分子;每分子G5 PAMAM分别连接了16,30和37个PEG分子。随着PAMAM的PEG化程度提高,其溶血毒性显著减小,复合MTX的量增多。PAMAM-PEG/MTX在10和1mmol·L^-1(pH 7.4)的Tris-HCl缓冲溶液中表现出缓释效果,但加入Nacl后释放加快。放置3个月后,复合物中MTX含量略有下降,药物释放未发生变化。结论与PAMAM相比,PAMAM-PEG的溶血毒性显著降低,并具有一定缓释效果,有望成为一种新型给药载体材料。     

聚乙二醇化葛根素化学结构初步鉴定

采用紫外、红外、氢核磁、碳核磁光谱联用技术对聚乙二醇(PEG)化葛根素的化学结构进行初步鉴定,结果推测2个PEG高分子(分子量:4700 Da)分别与葛根素葡萄糖基上的3″-OH和6″-OH仲羟基酯键结合。首次采用光谱联用技术对PEG高分子修饰物进行化学结构的初步鉴定。     

PEG修饰介孔硅纳米粒子负载丹参素的体外控制释放研究

目的设计制备一系列PEG修饰的介孔硅纳米粒子(MSNs-PEG),用于负载丹参素的药物传输载体。方法通过与硅烷偶联剂共水解缩合的方法,在介孔硅纳米粒子(MSNs)中引入数量可控的叠氮基,然后通过点击化学的方法,在MSNs表面引入数量可控的PEG链段,并通过傅里叶转换红外线光谱(FTIR)、X射线粉末衍射(XRD)、Zeta电位和透射电子显微镜(TEM)等方法表征MSNs-PEG,通过MTT法对MSNs-PEG载体的安全性进行初步评价,体外释放实验考察MSNs-PEG负载丹参素的释放规律。结果 PEG能够有效、可控地接枝到MSNs上,使MSNs-PEG具有良好的水分散性和稳定性。通过负载丹参素实验发现,MSNs-PEG对丹参素的负载率较高,其载药量和包封率分别为6.8%和22.8%。体外释放规律发现,PEG的接枝改变了药物的释放规律,能够有效延长丹参素的释放时间;随着PEG接枝量(质量分数)的提高,能够有效控制丹参素的释放速率。结论点击化学法能够有效地控制PEG接枝量(质量分数),并有效地控制丹参素的释放速度,方法简单易行。     

伊马替尼胶束的制备与体外克服肿瘤耐药性的研究

目的 伊马替尼(imatinib,IMN)包埋于托可索仑(tocofersolan,TPGS)胶束中,以提高其水溶性,并对其理化性质进行表征,及与人源耐药细胞株MCF-7/ADR的作用效果。通过TPGS胶束运输IMN进入细胞,可克服肿瘤细胞的多药耐药性,提高抗肿瘤效果,为进一步体内药效研究提供基础。方法 采用薄膜分散法制备IMN-TPGS胶束,对其粒径、电位、形态、载药量和包封率及体外释放行为进行表征,考察该胶束对MCF-7/ADR细胞的抗肿瘤效果。结果 IMN-TPGS胶束平均粒径为(22.69±2.39)nm,表面呈电中性,外观圆整,载药量为(1.55±0.06)%,包封率为(63.49±2.42)%;具有较高的耐稀释性,血清稳定性和冻干-复溶稳定性;在体外释放72 h后,累积释放度近100%,释放速率缓慢;IMN-TPGS胶束对MCF-7/ADR的IC₅₀为12.27 μmol·L^-1,细胞毒性大,细胞内药物含量高,可诱导近半数细胞凋亡。结论 IMN-TPGS胶束粒径均一,分散性良好,稳定性高,具有较强抗稀释性,有利于体液长循环,对耐药细胞株有明显的抗肿瘤效果,在一定程度上可以克服其多药耐药性。     

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??OBJECTIVE To prepare heparan sulfate-vitamin E succinate (HDV) amphipathic copolymers and explore the pharmaceutical properties of doxorubicin (DOX)-loaded HDV copolymer micelles (DOX/HDV). METHODS HDV copolymers were prepared by amide reaction and its structure was confirmed by ¹H-NMR. DOX/HDV micelles were prepared by ultrasonic method. The particle size, morphology, Zeta potential, drug loading, entrapment efficiency, and in vitro drug release and cytotoxicity were evaluated. RESULTS HDV amphipathic copolymers were synthesized successfully. The particle size, PDI value and Zeta potential of drug-loaded micelles were (105.0??7.3) nm, (0.239??0.484) and (-21.4??2.6) mV, respectively. The encapsulation and drug loading rate were (76.22??0.76)% and (9.53?? 0.58)%, respectively. The results of drug release test in vitro showed that DOX was released slowly from the micelles. Cytotoxicity experiments indicated that blank micelles had no apparent toxicity against both tumor cells and normal cells. However, DOX/HDV micelles could inhibit the tumor cells growth obviously. CONCLUSION HDV copolymers can effectively load DOX with properties of drug sustained release and enhanced cytotoxicity against tumor cells in vitro, which indicates that HDV may be a potential candidate for cancer therapy.     

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??OBJECTIVE To enhance the anticancer activity of doxorubicin(DOX) by conjugating DOX and vitamin E succinate (VES) and loading the conjugate into hyaluronic acid-octadecylamine (HA-C₁₈) copolymer micelles.METHODS DOX and VES were conjugated by amide reaction.DOX-VES/HA-C₁₈micelles were prepared via a probe-type ultrasonication technique.The morphology of the micelles was determined using a transmission electron microscopy (TEM).Dynamic light scattering (DLS) technique was used to determine the particle size distribution, hydrodynamic diameters, and stability of the micelles.Ultracentrifugation was exploited for measuring the drug loading (DL) and encapsulation efficiency (EE), and the in vitro release was investigated using a dialysis tubing.The cellular uptake and cellular distribution of drug-loaded micelles in MCF-7 cells were observed by fluorescence microscope, and the fluorescence intensity of DOX was evaluated by flow cytometer.The cytotoxicity of free DOX and drug-loaded micelles was tested by MTT assay against MCF-7 cells.RESULTS DOX-VES/HA-C₁₈ showed a nearly spherical morphology and good stability in PBS (pH 7.4) and 10% FBS.The particle size and zeta potential were (184.6??9.42) nm and (-20.7??1.23) mV, respectively.The DL and EE were (15.8??2.85)% and (94.2??1.32)%, respectively.DOX-VES/HA-C₁₈had a good controlled drug release property.Furthermore,DOX-VES/HA-C₁₈with accumulation in nucleipresented higher anti-tumor activity than free DOX and DOX/HA-C₁₈. CONCLUSION DOX-VES conjugate has synergistic anti-tumor effect and good application prospects.     

PLGA-PEG-PLGA温敏水凝胶包载多柔比星脂质体用于治疗小鼠骨肉瘤的研究

目的 制备聚乳酸乙醇酸-聚乙二醇-聚乳酸乙醇酸共聚物(PLGA-PEG-PLGA)水凝胶包载的多柔比星(Doxorubicin,DOX)脂质体的复合载体,并考察其体外性质和抑瘤效果。方法 采用水化薄膜法制备DOX脂质体,考察其粒径分布和包封率,再利用PLGA-PEG-PLGA水凝胶包载制备得到的DOX脂质体得到DOX-Lip-Gel复合载体,考察其体外释放、黏性测试以及对荷瘤小鼠的治疗效果。结果 制备得到的DOX-Lip的粒径约为(89.3±4.7) nm,包封率约为(85.3±2.6)%,PLGA-PEG-PLGA水凝胶在25 ℃处于溶液状态,而在37 ℃时可凝固成胶,黏性测试结果表明水凝胶的相变温度约为30 ℃。并且水凝胶聚合物具有良好的生物相容性,在体内可以缓慢的降解。与对照组相比,DOX-Lip-Gel可以缓慢的释放药物,且释放期长达200 h。体内抑瘤实验表明DOX-Lip-Gel具有更好的抗肿瘤效果。结论 制备得到的DOX-Lip-Gel对荷瘤小鼠进行瘤周给药,对抑制骨肉瘤在小鼠体内的增长具有显著的抑制作用。     

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??OBJECTIVE To prepare paclitaxel / oleyl chitosan nanoparticles (PTX / OCS-NPs) and to examine its physicochemical properties and acute lung toxicity. METHODS The morphology and size were determined by transmission electron microscope (TEM). The average diameters and polydispersity index were evaluated by dynamic light scattering (DLS). Encapsulation efficiency (EE) and in vitro release were determined by high performance liquid chromatography (HPLC). RESULTS The RESULTS of PTX/OCS-NPs were spherical in shape, uniform particle size and dispersed uniformly. The diameters of NPs were(292.4??20)nm, PDI less than 0.246 and Zeta potential was about 25 mV. The drug loading of PTX was 15.06%. The encapsulation efficiency of PTX was 48.96%. In vitro release study showed that the cumulative release of PTX from NPs were 41.41% and 56.23% respectively, within 48 h in phosphate buffered saline (PBS) pH 7.4 and pH 4.5. Acute toxicity showed that there was no change in the number of white blood cells in the blood, and the content of LDH in the bronchoalveolar lavage fluid was not changed. The RESULTS indicated that the drug delivery system has a good biosafety and biocompatibility. CONCLUSION PTX / OCS-NPs have excellent physicochemical properties, high drug loading, with sustained release, no acute lung toxicity, that is expected to be a good delivery of paclitaxel and other difficult anti-cancer drug delivery system.     

聚(2-乙基-2-噁唑啉)-胆固醇碳酸甲酯修饰的多西紫杉醇pH-敏感胶束的构建与性质考察

目的 利用聚(2-乙基-2-噁唑啉)-胆固醇碳酸甲酯[poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate,PEOz-CHMC,简称PC]构建多西紫杉醇(docetaxel,DOC)纳米胶束,并对其进行性质考察。方法 利用芘荧光探针法测定PC的临界胶束浓度。利用薄膜分散法制备DOC-PC胶束(DOC-PC micelles,DOC-M),对DOC-M的粒径、形态、包封率等进行表征。采用透析法考察DOC-M的药物释放,并模拟肿瘤微环境考察DOC-M的稳定性和pH敏感性。通过MTT法评价DOC-M对体外HeLa细胞的抑制作用。利用流式细胞仪定量观察胶束对HeLa细胞的摄取情况。结果 PC的临界胶束质量浓度为9.26 μg·mL^-1(4.63×10^-6mol·L^-1)。DOC-M的粒径小于130 nm,外观呈类球形,分布均匀,Zeta电位为(-7.32±0.98)mV。X-射线粉末衍射(XRD)和红外光谱(IR)结果表明,DOC被成功包封于胶束中,DOC-M的包封率为(80.55±2.44)%。体外药物释放和胎牛血清稳定性结果实验表明,DOC-M的pH敏感性和稳定性良好。细胞抑制实验结果表明,在微酸条件下DOC-M的细胞抑制作用更强。细胞摄取实验分析,DOC-M具有较低的毒性,显著地促进药物的细胞摄取。结论 DOC-M表现出良好的稳定性和pH敏感性,以及较低毒性和较好的载药能力,有望成为药物递送的良好载体。     

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??OBJECTIVE To synthesize hyaluronic acid-octadecene (HOY) copolymers by terminal thiolation modification of hyaluronic acid (HA), prepare doxorubicin-loaded micelles and investigate its pharmaceutical characteristics. METHODS HOY copolymers were synthesized through Michael addition reaction. The doxorubicin-loaded copolymer micelles were prepared with ultrasonic method, then the particle size, Zeta potential, encapsulation efficiency, drug loading efficiency and in vitro release behavior were studied. RESULTS HOY copolymers were synthesized successfully. The particle size and Zeta potential of the drug-loaded micelles were (237.2??2.7) nm and (-22.37??0.38) mV, and the encapsulation efficiency and drug loading rate were (89.8??0.011)% and (5.4??0.007)%, respectively. Moreover, the accumulative release of doxorubicin in vitro was about 70% in 48 h, indicating that the drug was released slowly from the micelles. CONCLUSION This study develops a new micellar system based on terminal modified HA, and provides a reference for the study of HA nanocarrier.
     

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??OBJECTIVE To prepare atorvastatin-loaded tetracycline-PEG-PLGA(TC-PEG-PLGA/ATO) polymeric micelles, and investigate its pharmaceutical characteristics and targeting function in vitro. METHODS The amphiphilic TC-PEG-PLGA conjugate was synthesized via an esterification reaction and identified by the ¹H-NMR. Water insoluble atorvastatin was loaded on TC-PEG-PLGA conjugate micelles via dialysis method. The morphology of TC-PEG-PLGA/ATO micelles was observed under transmission electron microscope. The particle size distribution and Zeta potential of TC-PEG-PLGA/ATO micelles were determined by dynamic light scattering method. The drug loading and encapsulation efficiency were measured by HPLC, and in vitro release behavior was investigated via dialysis method. In vitro cytotoxicity was assessed via MTT assay, and bone-targeting activity was investigated via binding to the hydroxyapatite powder. RESULTS TC-PEG-PLGA/ATO micelle was prepared successfully, and its particle size and Zeta potential were (47.2??4.7) nm and (-14.25??0.31) mV. The encapsulation efficiency and drug loading rate were(98.2??1.51)% and (8.71??0.23)%, respectively. Moreover, the accumulative release of ATO in vitro was about 70% in 48 h, which indicated that the drug was released slowly from the micelles. In vitro cell evaluation showed that TC-PEG-PLGA conjugate micelles were great biocompatibility with MC3T3-E1 cells within the concentration range of 100-500 ??g??mL^-1. In vitro targeting performance indicated that the proportion of the TC-PLGA NPs bound to Hap(87.94%) was greater than the bound proportion of PLGA NPs(18.59%). CONCLUSION The TC-PEG-PLGA/ATO micelles exhibit small partical size and good stability, and significantly increased ATO content in aqueous solution. TC-PEG-PLGA/ATO micelles have good delayed release behavior, safety and binding efficacy to the hydroxyapatite powder.     

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??OBJECTIVE To prepare aziditaxel-loaded mPEG-PLA polymeric micelles, investigate its pharmaceutical characteristics and study its anti-tumor effects in vitro. METHODS Aziditaxel-loaded polymeric micelles were prepared by thin-film dispersion method. The morphology of aziditaxel-loaded micelles was observed under transmission electron microscope. The particle size distribution and Zeta potential of aziditaxel-loaded micelles were determined by dynamic light scattering method using a Malvern Zetasizer Nano ZS90 analyzer. The technical reproducibility and reconstitution stability of aziditaxel-loaded micelles were also checked. The drug loading and encapsulation efficiency were measured by HPLC. Dialysis method was used to investigate the in vitro release of aziditaxel-loaded micelles, and the release manner was fitted using the mathematic models. The in vitro anti-tumor activities were evaluated by proliferation inhibition and cycle block experiment. RESULTS Aziditaxel-loaded polymeric micelles were prepared successfully. Aziditaxel-loaded polymeric micelles showed spherical shape with a mean particle size of 24.50 nm, polydispersity index of 0.117 and Zeta potential of -10.06 mV. The mean drug loading and entrapment efficiency were (16.00??0.15)% and (95.80??0.10)%, respectively. The preparation reproducibility was fine, and the reconstitution solution of lyophilized preparation of aziditaxel-loaded polymeric micelles maintained stable within 6 h. The release behavior of aziditaxel-loaded micelles conformed to the ambiexponent model. Drug-loaded micelles could obviously inhibit the proliferation of MCF-7 breast cancer cell lines in vitro, and induce significant G₂/M cycle arrest and apoptosis on MCF-7 cancer cells. CONCLUSION Aziditaxel-loaded mPEG-PLA polymeric micelles are successfully prepared. The preparation method is simple, and the pharmaceutical properties of the products conform to the requirements of the subsequent study. The prepared aziditaxel-loaded polymeric micelles exhibit good application prospect with favourable in vitro anti-tumor activities.