Bleeding gastric varices： Results of endoscopic injection with cyanoacrylate at King Chulalongkorn Memorial Hospital

AIM: To evaluate the efficacy and safety of gastric varices injection with cyanoacrylate in patients with gastric variceal bleeding. METHODS: Twenty-four patients (15 males, 9 females) with gastric variceal bleeding underwent endoscopic treatment with cyanoacrylate injection. Successful hemostasis, rebleeding rate, and complications were retrospectively reviewed. Followed up endoscopy was performed and repeat cyanoacrylate injection was given until gastric varices were obliterated. RESULTS: Seventeen patients achieved definite hemostasis. Of these, 14 patients had primary success after initial endoscopic therapy. Ten patients developed recurrent bleeding. Repeated cyanoacrylate injection stopped rebleeding in three patients. Transjugular intrahepatic portosystemic shunt (TIPS) was performed to control rebleeding in one patient which occured after repeat endoscopic therapy. Six patients died (three from uncontrolled bleeding, two from sepsis, and one from mesenteric vein thrombosis). Minor complications occurred in 11 patients (six epigastric discomfort and five post injection ulcers). Cyanoacrylate embolism developed in two patients. One of these patients died from mesenteric vein thrombosis. The other had pulmonary embolism which resolved spontaneously. Advanced cirrhosis and hepatocellular carcinoma (HCC) were major risk factors for uncontrolled bleeding. CONCLUSION: Endoscopic treatment for bleeding gastric varices with cyanoacrylate injection is effective for immediate hemostasis. Repeat cyanoacrylate injection has a lower success rate than the initial injection. Cyanoacrylate embolism is not a common serious complication.     

氰基丙烯酸正丁酯纳米载体促进紫杉醇粒抗脑胶质瘤作用的实验研究

目的:动物实验水平研究聚氰基丙烯酸正丁酯纳米载体促进紫杉醇粒抗脑胶质瘤的作用。方法:1紫杉醇-聚氰基丙烯酸正丁酯纳米粒悬液的制备。2制备胶质瘤模型,制备的胶质瘤模型随机分成四组,每组20只,Ⅰ组注射生理盐水、Ⅱ组注射紫杉醇、Ⅲ组注射PBCA+NP、Ⅳ组注射紫杉醇+PBCA+NP,15d后观察Wistar大鼠的变化,观察肿瘤病理切片,检测肿瘤细胞的凋亡率。结果:1Wistar大鼠的生存状态,Ⅳ组好于其它三组。2Ⅱ组和Ⅲ组Wistar大鼠脑胶质瘤血管的减少和坏死肿瘤组织比Ⅳ组少。3Wistar大鼠脑胶质瘤调亡率Ⅳ组高于Ⅱ组、Ⅲ组,具有统计学显著差异(P<0.05)。结论:聚氰基丙烯酸正丁酯纳米载体明显提高紫杉醇抗Wistar大鼠脑胶质瘤的作用。     

罗哌卡因乳酸羟基乙酸共聚物纳米粒的制备及体外释药研究

目的局部麻醉药体内生物半衰期短,且局部组织的高浓度极易造成药物经血管吸收入血产生中枢神经和心血管毒性反应。文中旨在制备罗哌卡因乳酸羟基乙酸共聚物纳米粒,优化工艺,并对其体外性质进行研究。方法以乳酸羟基乙酸共聚物(PLGA)为载体,采用O/W乳化溶剂挥发法制备包载罗哌卡因(RVC)的PLGA纳米粒,以纳米粒的粒径、包封率及载药量为考察指标,采用星点设计-效应面法优化制备工艺,进行体外释放研究。结果以优化处方制备的罗哌卡因乳酸羟基乙酸共聚物纳米粒(RVC-PLGA-NPS),外观光滑圆整,平均粒径为(331.21±2.11)nm,载药量、包封率分别为(13.81±1.35)%、(74.82±2.53)%。体外释药研究表示,96 h累积释药率达73%,释放曲线符合Higuchi方程。结论乳化溶剂挥发法适用于RVC-PLGA-NPS的制备,制得的纳米粒形态圆整,在体外具有明显的缓释行为。     

PLGA-PEG多孔载药微球的制备及超声波对其释药行为的影响研究

目的:以伊文思蓝为被包封物制备聚乳酸(LA)-羟基乙酸(GA)-聚乙二醇(PEG)嵌段共聚物(PLGA-PEG,PLGE)多孔载药微球,并研究超声波对药物体外释放的影响。方法:以LA-GA-PEG(63.00∶27.50∶9.50,m/m/m)为原料制备PLGE;以二氯甲烷为有机相,采用复乳法制备PLGE包封的伊文思蓝多孔载药微球。采用扫描电子显微镜对载药微球的形态进行观察;采用紫外分光光度法测定伊文思蓝的载药量和包封率;考察低频率(20 k Hz,40 W)超声波对其药物累积释放度的影响。结果:所制备的多孔载药微球成球规整,彼此不粘连,表面孔隙均匀,载药量为0.38%,包封率为89.92%;15 min时的累积释放度在超声和未超声条件下分别为2.76、0.91μg/mg。结论:PLGE可用作微球药物的载体,低频率超声波可促进微球内药物的释放。     

关节腔注射用氟比洛芬PLGA缓释微球的制备及体外释放特性研究

目的制备关节腔注射用氟比洛芬(FP)缓释微球并研究其体外释药特性。方法以聚乳酸-羟基乙酸共聚物(PLGA)为材料,采用乳化-溶剂挥发法制备微球;正交设计法优化微球的制备工艺;采用透析法研究体外释药特性,UV法测定FP的含量。结果正交试验表明,PLGA的浓度是影响微球包封率的非常显著性因素。微球粒径范围为1.5~24.3μm,平均粒径为10.6μm,载药量为7.1%(W/W),包封率为92.7%,体外释药符合Higuchi方程,释放时间显著延长。结论本法制备的FP微球粒径大小适宜,具有明显的缓释作用,符合关节腔注射给药设计要求。     

大鼠体内大脏器创伤模型涂布康派特?医用胶后生物反应观测

目的：评价康派特?医用胶对大鼠内脏创面止血后的安全性及其体内降解情况。方法：大鼠随机分为空白对照组,手术对照组和手术涂胶组,给胶组分别给予8μL或40μL康派特?医用胶。术后动物进行临床症状观察,体重、摄食量测定,血常规、血清生化学、脏器重量和组织病理学检查。结果：各项指标均未见与康派特?医用胶相关毒性反应;6个月组织病理学检查可见胶体被纤维结缔组织逐渐分割,多核巨细胞和炎症细胞参与异物降解。结论本实验条件下,未见康派特?医用胶对大鼠机体有毒性作用,胶体在大鼠体内6个月开始降解。     

乙型肝炎免疫球蛋白聚氰基丙烯酸正丁酯纳米粒抑制HBsAg、HBV DNA分泌的体外实验

Objective To investigate the inhibitive activities of hepatitis B immunoglobulin(HBIG)poly(butylcynaoacrylate)nanoparticles(HBIG-PBCA-NP)to hepatitis B surface antigen(HBsAg)and hepatitis B virus(HBV)DNA secretions using HBV infected cell model in vitro.Methods HepG 2.2.15 cells were cultured with media containing HBIG-PBCA-NP or HBIG for several days,or cultured with HBIG-PBC-NP and HBIG for 2 days and without HBIG-PBCA-NP and HBIG from day 3.The supernatants at different time points were collected for quantitative detection of HBsAg and HBV DNA.The comparisons between groups were done by variance analysis.Resalts Secretions of HBsAg and HBV DNA in supernatants of HepG2.2.15 cultured with 0.1-10.0 IU/mL of HBIG-PBCA-NP and HBIG were inhibited significantly compared with control group.HBsAg titers and HBV DNA levels in supernatants of HBIG-PBCA-NP group and HBIG group cultured with media without HBIG-PBCA-NP and HBIG kept decreasing at day 5 and 7,then rebounded at day 9 and 11.HBsAg titera in supernatants of 0.1,1.0,5.0 IU/mL HBIG-PBCA-NP group were all significantly different from those in HBIG group at day 9[(31.31±1.98)μg/L vs(40.62±2.99)μg/L,(23.79±1.31)μg/L vs(36.51±2.12)μg/L,(19.91±1.74)μg/L vs(33.03±1.65)μg/L;F=412.24,P＜0.01].Couclusion HBIG-PBCA-NP can inhibit secretions of HgsAg and HBV DNA in vitro,which is more effective than HBIG.     

乙型肝炎免疫球蛋白聚氰基丙烯酸正丁酯纳米粒抑制HBsAg、HBV DNA分泌的体外实验

Objective To investigate the inhibitive activities of hepatitis B immunoglobulin(HBIG)poly(butylcynaoacrylate)nanoparticles(HBIG-PBCA-NP)to hepatitis B surface antigen(HBsAg)and hepatitis B virus(HBV)DNA secretions using HBV infected cell model in vitro.Methods HepG 2.2.15 cells were cultured with media containing HBIG-PBCA-NP or HBIG for several days,or cultured with HBIG-PBC-NP and HBIG for 2 days and without HBIG-PBCA-NP and HBIG from day 3.The supernatants at different time points were collected for quantitative detection of HBsAg and HBV DNA.The comparisons between groups were done by variance analysis.Resalts Secretions of HBsAg and HBV DNA in supernatants of HepG2.2.15 cultured with 0.1-10.0 IU/mL of HBIG-PBCA-NP and HBIG were inhibited significantly compared with control group.HBsAg titers and HBV DNA levels in supernatants of HBIG-PBCA-NP group and HBIG group cultured with media without HBIG-PBCA-NP and HBIG kept decreasing at day 5 and 7,then rebounded at day 9 and 11.HBsAg titera in supernatants of 0.1,1.0,5.0 IU/mL HBIG-PBCA-NP group were all significantly different from those in HBIG group at day 9[(31.31±1.98)μg/L vs(40.62±2.99)μg/L,(23.79±1.31)μg/L vs(36.51±2.12)μg/L,(19.91±1.74)μg/L vs(33.03±1.65)μg/L;F=412.24,P＜0.01].Couclusion HBIG-PBCA-NP can inhibit secretions of HgsAg and HBV DNA in vitro,which is more effective than HBIG.     

葛根素磷脂复合物纳米粒的制备及体外评价

目的制备葛根素磷脂复合物,以聚氰基丙烯酸正丁酯(PBCA)为载体材料,制备葛根素磷脂复合物纳米粒,并对其进行体外评价。方法采用界面缩合聚法制备纳米粒。以复合率、包封率和载药量为评价指标,通过单因素和正交试验法优选处方和工艺。结果葛根素磷脂复合物的最佳处方及工艺:反应溶剂为无水乙醇,葛根素与磷脂的投料比为1∶2;葛根素磷脂复合物纳米粒的最佳处方及工艺:pH=3.0、α-氰基丙烯酸正丁酯(α-BCA)的浓度为0.8%、V油相∶V水相=1∶60、葛根素磷脂复合物的投药量为1.0 mg。制备的纳米粒平均粒径为(115.1±3.45)nm、包封率为(90.03±1.80)%、载药量为(11.80±0.12)%。体外释药在24 h累积释放量约为80%。结论本研究所制备的葛根素磷脂复合物纳米粒包封率和载药量高、性质稳定、体外释药具有缓释行为。     

聚乳酸⁃羟基乙酸共聚物在牙髓疾病治疗中的应用前景

材料学的发展对牙髓疾病的治疗有重要意义,聚乳酸?羟基乙酸共聚物[poly(lactic?co?glycolic acid),PLGA]是一种被广泛应用于生物医用材料制备的有机高分子化合物。近年来,作为载药/分子系统和组织再生支架在牙髓疾病治疗中展现出应用前景,本文将对PLGA在牙髓疾病治疗中的应用作一综述,为其进一步开发利用提供参考。文献复习结果表明,PLGA作为药物/分子输送系统主要应用于盖髓材料、根管消毒剂和根尖诱导成形剂的改良。PLGA改良盖髓材料能延长药物作用时间、降低毒性;改良根管消毒剂能实现药物缓释,使药物深入更细微的结构,与致病菌有更广泛的接触;改良根尖诱导成形剂能为根尖诱导提供更便捷的给药方式。PLGA作为组织工程支架主要应用于牙髓再生的研究,通过PLGA物理性能、作用环境的不断优化为种子细胞提供更适宜增殖分化的微环境。如何合理利用PLGA的优势,研制出更适宜根管内应用的材料,还需要进一步的研究。