131I-c(RGD)2在原位荷脑胶质瘤裸鼠模型中的靶向定位研究

目的 对131I-c(RGD)2在原位荷脑胶质瘤动物模型中的靶向定位作用进行研究,以探讨其应用于脑胶质瘤诊断与治疗的可能性.方法 采用U87-MG人脑胶质瘤细胞接种在裸鼠右脑尾状核内,建立了原位荷脑胶质瘤动物模型;采用氯氨T法将131I标记c(RGD)2,于原位荷脑胶质瘤裸鼠中进行生物分布研究,计算131I-c(RGD...     

氟嗪酸的药代动力学

氟嗪酸为第三代哆诺酮类药物，对Ｇ，Ｇ菌均有效，口服片剂吸收良好。血浆蛋白结合率为２５．０±５．７％，ｌｈ～２ｈ后达到最大血药浓度，绝对生物利用度接近１００％，分布容积为１。３～１．７Ｌ／ｋｇ，半衰期为４．９ｈ～５．５ｈ，组织液体穿透率高，肾清除率高，并且主要以原形尿排．     

全身振动对中药轻粉(Hg2Cl2)在小鼠体内的药代动力学的影响

本文研究了小鼠单次轻粉灌胃给药后全身振动对小鼠体内血液、肝、肾、脑组织中含汞量分布的影响，发现50 Hz组的全身振动血液、肝、肾、脑组织吸收峰值均比对照组提前，20 Hz组的全身振动血液、肾、脑组织吸收峰值比对照组提前，且50 Hz组的血液、脑组织中吸收峰值显著高于20 Hz组；小鼠连续灌胃给药5天后进行测定，发现50 Hz振动组肝、肾、脑组织的含汞量显著低于对照组。结果表明：全身振动能加快小鼠对轻粉的吸收和消除，抑制汞在各组织中的蓄积。     

甲磺酸齐拉西酮注射液人体药代动力学

齐拉西酮通过抵抗多巴胺D2和5HT2受体而显现治疗精神病的疗效。文献报道单剂肌注齐拉西酮的生物利用度为100％．达峰时间为60min。t1／2为2～5h。本实验研究了重庆圣华日曦药业有限公司研制甲磺酸齐拉西酮注射液人体药代动力学。     

中华眼镜蛇毒组份Ⅲ的药代动力学及组织分布研究

目的:观察中华眼镜蛇(Najanajaatra)蛇毒组份Ⅲ在兔体内的药代动力学过程和在小鼠体内的分布状况。方法:用氯胺-T法对眼镜蛇毒组份Ⅲ进行碘化标记,用放射性核素示踪动力法检测血液中的药物浓度,以放射性参与量(脏器与血液放射比)的比值作为组份Ⅲ在组织中分布的依据。结果:兔静脉注射眼镜蛇毒组份Ⅲ75、150和300μg／kg3个剂量后,快分布相半衰期T_1/2α为39.6-42.5min,慢分布相半衰期T_1/2β为16.8-17.3h,消除相半衰期T_1/2γ为21.7-22.1h。小鼠尾静脉注射[¹²⁵Ⅰ]-组份Ⅲ后,2h及4h放射性参与量大于1的器官为肝脏、肾脏、肺脏、心脏和肌肉,其中以肾脏分布最高,且4h放射性参与量高于2h。结论:兔静脉注射组份Ⅲ3个剂量后,血药-时间曲线经3P87药动学程序拟合符合三房室模型特征,3个时相的半衰期各剂量组之间无显著差异,曲线下面积(AUC)与剂量成正比,表明药物在兔体内的分布和消除为一级线性动力学过程。小鼠静注组份Ⅲ后2h,以肾脏分布最高,肝脏与肺脏的放射性参与量也较高,尿中含量很高。     

盐酸西替利嗪片的人体药代动力学研究

目的 建立测定盐酸西替利嗪片的人体药代动力学研究.方法 采用高效液相色谱法,测定20名健康男性志愿者口服盐酸西替利嗪片的血浆药物浓度:结果盐酸西替利嗪半衰期为(7.42±1.50)h,达峰时间为(1.06±0.42)h,峰浓度为(0.46±0.10)μg/mL,滞后时间为(1.25±0.47)h.结论 高效液相色谱方法结果准确,灵敏度高,能满足盐酸西替利嗪人体药代动力学研究的需要,可广泛应用于临床.     

局麻药药代动力学研究进展

药物对映体结构特异性对局麻药药代动力学的各个过程都有着很大影响,包括药物的吸收、蛋白结合率、代谢等。近年研究较多的罗哌卡因和左旋布比卡因作为单一的左旋对映异构体,因其良好的局麻效应和较小的全身毒性正引起广泛的关注。     

法莫替丁颗粒、片剂药代动力学及生物利用度研究

本文报道8名成年男性健康受试者单剂口服法莫替丁颗粒、片剂药代动力学及相对生物利用度比较。8名受试者接受单剂量(40mg)交叉给药(颗粒剂和片剂)后所得药时曲线符合一室模型。其颗粒剂和片剂的平均药代动力学参数分别为:血浆药物峰浓度:110.29±23.59与112.95±23.36μg/L,药物达峰时间:1.66±0.59与1.97±0.53h,消除半衰期:3.53±0.33与3.18±0.53h,药—时曲线下面积:737.11±147.09与721.42+100.94μg/L·h。其相对生物利用度以片剂为100％,颗粒剂的相对生物利用度为102.96±20.05％。     

药代动力学与血友病的个体化预防治疗

血友病是一种由基因突变导致凝血因子缺乏引起的出血性疾病.由于血友病管理理念的不断发展,现在首选的治疗方案是预防治疗.凝血因子在不同患者体内的药代动力学以及不同患者的出血类型存在明显差异,可以根据患者药代动力学相关数据为其量身定做治疗方案,尽量减少患者的不便、不适以及尽可能避免高昂的治疗费用.因此,个体化预防是重要的.它...     

民族药广枣有效部位健康家兔体内药代动力学研究

目的：明确广枣有效部位(CEE)的药代动力学特征。为指导临床合理用药和初步揭示药效物质基础提供数据支持。方法：以恒流反相离子对色谱法同时测定给药后健康家兔血清中出现的三个特异性成分(没食子酸GC、原儿茶酸PC和一特异性色谱峰所代表的物质)。结果：GC和PC药代动力学行为分别符合二室开放模型和一室开放模型。特异性色谱峰所代表物质药代动力学行为符合二室开放模型。     

Acute and Subchronic Toxicity Study of Tud-Rak-Ka-Sai-Puu Recipe in Rats

Acute and subchronic toxicities of Tud-Rak-Ka-Sai-Puu (TR) recipe were studied in male and female rats. After 14 days of a single oral administration of test substance (5,000 mg/kg body weight), measurement of the body and organs weights, necropsy and health monitoring were performed. No signs and differences in the weights and behavior were observed relative to the control rats, suggesting that TR recipe in the dose of 5,000 mg/kg body weight does not produce acute toxicity. The subchronic toxicity was determined by oral feeding in male and female rats daily with the test substance at 2, 20, 200 and 2,000 mg/kg body weight for 90 days. No defects of animal behavior were observed in the test groups. Both test and control groups (on the 90^th day) as well as the satellite group (on the 118^th day) were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry, and microanatomy. These results together with the information of signs, behavior and health monitoring can lead to a conclusion that an oral administration of TR recipe at 2, 20, 200 and 2,000 mg/kg body weight for 90 days did not cause subchronic toxicity.     

RGD肽表面修饰聚苯乙烯及其细胞相容性研究

目的以聚苯乙烯二维平面为模板研究了蛋白表面修饰技术,构建具有生物活性的生物材料表面。方法采用物理包被法依靠疏水作用在PS表面架构明胶、胶原和RGD（精氨酸-甘氨酸-天冬氨酸）多肽的生物活性层。通过光电子能谱（XPS）分析修饰表面的元素含量变化,N元素含量显著提高,说明蛋白分子在表面存在。Bradford方法定量分析明胶、胶原和RGD多肽的表面吸附量。结果XPS证实了表面N原子的引入,存在酰胺键,确定蛋白分子存在于PS表面。结论动态接触角下降显著,证明修饰表面的亲水性得到提高。并在明胶、胶原和RGD多肽修饰表面接种人表皮细胞,对比考察其对细胞行为的影响,提高了细胞的黏附和增殖能力。     

Acute and Subchronic Toxicity of Chantaleela Recipe in Rats

Acute and subchronic toxicities of Chantaleela recipe were studied in both male and female rats. Oral administration of the extract at a single dose of 5,000 mg/kg body weight (5 females, 5 males) did not produce signs of toxicity, behavioral changes, mortality or differences on gross appearance of internal organs. The subchronic toxicity was determined by oral feeding the test substance at the doses of 600, 1,200 and 2,400 mg/kg body weight for 90 days (10 females, 10 males). No signs of abnormalities were observed in the test groups as compared to the controls. The test and control groups (on the 90^th day) and the satellite group (on the 118^th day) were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematological parameters, blood clinical chemistry and histopathology features. The results suggest that Chantaleela recipe did not cause acute or subchronic oral toxicities to female and male rats.     

人工合成RGD小肽对肝星状细胞分泌细胞外基质的影响

目的 :探讨精氨酰甘氨酰天冬氨酸肽 (Arg -Gly -Asp ,RGD)对肝星状细胞分泌细胞外基质 (extra cellularmatrix ,ECM)的影响。方法 :利用化学方法合成RGD ;应用胶原酶原位灌注法分离SD大鼠原代肝星状细胞 (hepaticstallatecell,HSC) ,接种培养 4 8h后 ,随机分成 4组 :①空白对照组 ;②转化生长因子 β1(transform inggrowthfactorβ1,TGFβ1)组 :只加TGFβ1(终浓度 5ng/ml) ;③RGD组 :只加RGD(终浓度 10 0 μg/ml) ;④联合加药组 :加RGD(终浓度 10 0 μg/ml)同时加TGFβ1(终浓度 5ng/ml)。连续培养 3d后 ,放射免疫分析细胞上清液各项ECM含量变化。结果 :与空白对照组相比 ,TGF β1组和联合加药组细胞上清液中透明质酸(hyaluronicacid ,HA)、层粘连蛋白 (laminin ,LN)和Ⅲ型前胶原 (procollagenⅢ ,PCⅢ )水平均显著增高 ,RGD组细胞上清中各项ECM水平则无明显改变 ;与TGFβ1组相比 ,联合用药组HSC细胞上清LN和PCⅢ水平明显降低。结论 :RGD明显降低HSC培养上清中LN和PCⅢ含量 ,表明RGD能抑制原代HSC合成及分泌ECM ,其机制可能与竞争性结合整合素有关。     

RGD-蜘蛛拖丝蛋白聚合物的生物合成与纯化

蜘蛛拖丝是自然界性能最好的蛋白质纤维之一 ,其独特的机械性能 ,良好的生物相容性和缓慢的可降解性 ,作为生物材料在组织工程领域有着潜在的应用前景。本文根据蜘蛛拖丝蛋白序列高度重复的特点 ,引入与细胞黏附有关的精氨酸 甘氨酸 天冬氨酸 (RGD)三肽 ,化学合成RGD 蜘蛛拖丝蛋白基因单体 ,通过头尾相连倍加构建策略 ,首次得到RGD 蜘蛛拖丝蛋白基因 8聚体和 16聚体。分别将这两种多聚体与原核高效表达载体 pET 30a( )连接 ,转化大肠杆菌BL2 1(DE3) pLysS ,用IPTG诱导表达。SDS PAGE图谱显示表达产物分子量分别为 35KD和 6 0KD ,与理论值基本相吻合 ;蛋白质印迹分析这两种表达产物均显示特异性。文中对表达产物的纯化方法进行了初步的摸索。     

RGD多肽化学修饰聚苯乙烯培养板的细胞相容性研究

目的 考察RGD多肽化学修饰聚苯乙烯培养板细胞相容性研究.方法 采用高锰酸钾硫酸溶液对聚苯乙烯表面进行氧化反应,生成羧基位点;水溶性碳二亚胺活化羧基,接枝明胶、胶原和RGD多肽.用红外光谱、X-射线光电子能谱(XPS)、动态接触角等研究了RGD化学修饰聚苯乙烯的变化,并考察了RGD化学修饰聚苯乙烯后细胞相容性的变化.结果 XPS结果证实了聚苯乙烯表面N原子的引入,RGD是共价键合在聚苯乙烯表面的.动态接触角下降显著,证明修饰表面的亲水性能提高.在修饰后的聚苯乙烯培养板种植入表皮细胞,结果显示提高了细胞的黏附和增殖能力.结论 聚苯乙烯表面进行RGD化学修饰,有利于提高细胞在其表面的黏附和增殖能力,有望为免疫磁珠分离得到的高纯度内皮祖细胞提供良好的培养介质.     

cRGD肽二聚体对B16黑色素瘤细胞的体外抑制作用及在荷瘤鼠体内分布及显像研究

目的 探讨cRGD肽二聚体对B16黑色素瘤细胞的体外抑制作用及其在荷B16黑色素瘤细胞小鼠动物模型体内的分布及显像研究.方法 用MTT法检测不同浓度及作用时间cRGD肽二聚体对B16黑色素瘤细胞体外增殖能力的影响.采用直接标记法标记99 Tcm-c(RGD)2.建立荷B16黑色素瘤株动物模型,待肿瘤体积为1.0 ～ 1.5cm3左右时,分别于30min、1h、2h、3h、4h、5h及6h时,进行荷瘤鼠体内生物分布及动态显像研究.结果 cRGD肽二聚体浓度为500mg/L、作用48h时,对B16黑色素瘤细胞的增殖具有明显的抑制作用.室温下、ρ(SnCl2·2H20)=1 g/L、反应时间为30 min时,99Tcm-c(RGD)2的标记率可达(87.42±3.21)％,标记产物经Sephadex G10分离纯化后放射化学纯度大于95％;静脉注射后30min行小鼠全身SPECT显像,肿瘤部位可见明显显像剂聚集,但肿瘤与周围组织的对比度较低;延迟至6小时肿瘤仍清晰可见,且随时间延迟肿瘤与周围组织的对比度增高,此时肿瘤/血液为2.15±0.24,肿瘤/肌肉为5.07 ±0.03.结论 该结构cRGD肽二聚体对B16黑色素瘤细胞株具有一定的体外抑制作用,且动物体内肿瘤组织摄取率高,显像清晰,证明其可进一步应用于聚合物多肽靶向药物的研发.     

Synthesis of a novel polyurethane co-polymer containing covalently attached RGD peptide

The synthesis of a novel polyurethane block co-polymer containing a covalently attached, well-oriented RGD (Arg-Gly-Asp) peptide was explored. A poly(tetramethylene oxide) (PTMO)-based polyurethane was synthesized, and a bimolecular nucleophilic substitution reaction was then employed to incorporate ethyl carboxylate groups onto the polymer backbone (i.e. carboxylated polyurethane). Elemental analysis was used to determine the extent of carboxylation. The hexapeptide H-Gly-Arg-Gly-Asp-Ser-Tyr-OH was coupled to the carboxylated polyurethane via the formation of an amide bond. The attachment of the peptide was controlled by a protection-deprotection scheme. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopies were used to monitor the reactions. Sakaguchi assay and amino acid analysis confirmed that the RGD-containing peptide was successfully grafted onto the carboxylated polyurethane. This reaction scheme provides a new route for grafting end-linked, bioactive peptides onto polyurethanes.     

Acute Toxicity Study and Antipyretic Effect of the Brown Alga Turbinaria Conoides (J. Agardh) Kuetz

The active principles of brown alga, Turbinaria conoides (J.Agardh) Kuetz. (Sargassaceae) was extracted with n-hexane, cyclohexane, methanol and ethanol-water (1:1) and investigated for acute toxicity and antipyretic activity. Phytochemical analysis of the extracts revealed the presence of steroids, flavonoids and reducing sugars. Acute toxicity study was performed in Wistar rats after administration of extracts orally. No mortality was observed up to the dose of 5g/kg for methanol and ethanol-water (1:1) extracts whereas n-hexane and cyclohexane extracts were found to be toxic at the dose levels of 1g/kg and 2 g/kg respectively. In biochemical analysis, n-hexane, cyclohexane and ethanol-water (1:1) extracts caused a significant (P<0.01) increase in serum cholesterol, protein and alkaline phosphatase levels. In haematological studies, a significant difference was observed for cyclohexane and ethanol-water (1:1) extracts in polymorphs, lymphocytes and eosinophils when compared to the control. Antipyretic activity of extracts (100–400 mg/kg doses) was carried out on yeast-induced pyrexia in rats. Cyclohexane extract exhibited more significant antipyretic activity (P<0.01) than the other extracts at a dose of 200mg/kg (54.43%), which was comparable to that of paracetamol at a dose of 33 mg/kg. The findings validated the use of this brown alga in traditional cure of children''s fever.