鸦胆子油乳协同周剂量TX方案治疗晚期胃癌的疗效研究

摘 要 目的：评价鸦胆子油乳注射液协同周剂量TX方案治疗晚期胃癌的临床疗效。方法：42例晚期胃癌患者随机分为观察组（给予鸦胆子油乳注射液联合周剂量用剂量TX方案）19例和对照组（给予单纯周剂量TX方案化疗）23例。入组患者均至少接受2个周期以上的化疗。观察比较两组近期疗效、生活质量和生存期。结果：观察组近期有效率为63.2%,显著高于对照组的8.7%(P<0.05);观察组疾病控制率为94.7%,对照组为87.0%,差异无统计学意义( P>0.05)。观察组中位生存时间为741 d,显著高于对照组的359 d( P<0.05)。 结论：鸦胆子油乳注射液联合周剂量TX方案治疗晚期胃癌可明显提高患者化疗的近期疗效,延长患者的生存期。     

紫杉醇-油酸和鸦胆子油分子配型组装纳米乳给药系统研究

目的优化紫杉醇-油酸(PTX-OA)和鸦胆子油(BJO)分子配型组装纳米乳给药系统(PTX-OA/BJO CMNEs)的处方及制备工艺。方法通过酯化反应制备得PTX-OA并建立检测PTX-OA的HPLC方法。采用超声乳化法制备PTX-OA/BJO CMNEs。单因素实验选出对PTX-OA/BJO CMNEs粒径影响较大的3个因素,L16(43)正交试验以这3个因素油相质量浓度(A)、聚山梨酯-80用量(B)和超声功率(C)为考察因素,以平均粒径为评价标准,优选PTX-OA/BJO CMNEs的处方及制备工艺。对优选条件制备的PTX-OA/BJO CMNEs进行制剂学评价及体外细胞毒实验。结果 HPLC法检测PTX-OA在5~25μg/m L线性关系良好,回归方程Y=12.709 X+6.252 0,r=0.999 5。最优处方为油相质量浓度为6.50 mg/m L,聚山梨酯-80-油相比例为3.5∶6.5,超声乳化功率为120 W。制备的PTX-OA/BJO CMNEs外观良好,平均包封率为(100.6±1.9)%,平均粒径(108.7±2.3)nm,多分散系数(PDI)为0.232±0.038。透射电子显微镜(TEM)形态观察表明PTX-OA/BJO CMNEs粒径接近100 nm,分布较均一;其体外释放度在48 h达到67%。PTX-OA/BJO CMNEs溶液置于4℃,避光环境下保存60d,包封率、粒径基本保持不变,稳定性较好。体外细胞毒实验显示,BJO与PTX-OA联用对Hep G-2细胞生长抑制具有一定的协同作用。结论优化后的PTX-OA/BJO CMNEs制备工艺简单易行,且药物之间具有增强细胞毒作用,为PTX和BJO联合用药的抗肿瘤作用机制的研究奠定了基础。     

鸦胆子油乳联合阿帕替尼及替莫唑胺治疗复发性恶性脑胶质瘤

目的探讨鸦胆子油乳联合阿帕替尼及替莫唑胺治疗复发性恶性脑胶质瘤患者的临床疗效、免疫功能影响及不良反应。方法选取2016年6月至2018年12月期间郑州大学第一附属医院复发性恶性脑胶质瘤患者52例,随机分为2组,A组26例应用阿帕替尼及替莫唑胺治疗,B组26例应用鸦胆子油乳联合阿帕替尼及替莫唑胺治疗,比较2组临床疗效、免疫功能及不良反应。结果治疗后,B组客观缓解率为69.23%,高于A组的38.46%(P<0.05)。治疗后,A组CD3+T细胞、CD4+辅助性T细胞、CD4+/CD8+较治疗前显著降低(P均<0.05),而B组上述指标较治疗前显著升高(P均<0.05),且均显著高于A组(P<0.05)。治疗后,B组KPS评分高于治疗前,且高于A组(P均<0.05)。B组不良反应发生率低于A组,但差异无统计学意义(P>0.05),且不良反应轻微可耐受,对症处理后消失。B组6个月疾病无进展生存率65.4%、中位疾病无进展生存期7.56个月(95%CI:5.72~9.40个月)、中位总生存期10.14个月(95%CI:8.59~11.70个月),均明显高于A组的46.2%、5.78个月(95%CI:4.64~6.92个月)、8.73个月(95%CI:8.22~9.25个月)(P均<0.05)。结论鸦胆子油乳联合阿帕替尼及替莫唑胺治疗复发性恶性脑胶质瘤可提高近期临床治疗效果,调节患者免疫功能,改善其生活质量和生存,且安全性良好,值得临床应用推广。     

鸦胆子油乳注射液及配置后静脉输液的室温稳定性研究

目的 考察说明书中贮存条件要求冷藏,且须临用前即配即用的鸦胆子油乳注射液的原液和稀释后的静脉输液在室温(25 ℃)下的稳定性,为该药品的临床管理与使用提供依据。方法 模拟临床给药剂量和给药时间,考察性状、pH、渗透压、颗粒细度和油酸含量在室温下放置不同时间点的变化。结果 在室温下,鸦胆子油乳注射液原液放置72 h质量稳定,配置后静脉输液(30 mL∶250 mL 0.9%生理盐水)在24 h内各项理化指标均无明显变化。结论 鸦胆子油乳注射液在医院内部的短时间药物配送无需严格实施冷链管理;配置后静脉输液室温放置24 h稳定,无需“即配即用”。     

TUR-Bt术后膀胱内灌注鸦胆子油乳预防浅表性膀胱癌复发

目的观察鸦胆子油乳膀胱灌注预防浅表性膀胱癌经尿道膀胱肿瘤电切术(TUR-Bt)术后复发的疗效。方法187例浅表性膀胱癌TUR-Bt术后患者随机分为A组(85例)和B组(102例),A组应用鸦胆子油乳膀胱灌注,B组灌注丝裂霉素预防肿瘤复发。对两组患者随访3年,观察肿瘤复发及药物副作用情况。结果A组复发11例,复发率12.94%,较B组的34.31%显著降低(P<0.001),且副作用小(P<0.001)。结论TUR-Bt术后灌注鸦胆子油乳预防膀胱癌复发有良好效果。     

Antimalarial and cytotoxic quassinoids from the roots of Brucea javanica

Two new quassinoids, brujavanol A (1) and brujavanol B (2), along with five known quassinoids (3–7), were isolated from the roots of Brucea javanica. Their structures were elucidated by spectroscopic methods. The antimalarial and cytotoxic activities of the isolated compounds were also assessed. Compounds 1 and 2 exhibited significant in vitro cytotoxicity against human oral cavity cancer (KB) cells with IC₅₀ values of 1.30 and 2.36 μg/ml, respectively, whereas compound 3 showed excellent antiplasmodial activity against the Plasmodium falciparum strains, K1 (IC₅₀ = 0.58 μg/ml).     

Suppression of human hepatocellular cancer cell proliferation by Brucea javanica oil-loaded liposomes via induction of apoptosis

Introduction

Hepatocellular carcinoma (HCC) is a type of malignancy with high incidence and poor prognosis. Brucea javanica is extracted from Simaroubaceae plants. It is found to have low toxicity but high anti-cancer efficiency. The aim of this study is to determine the effects of Brucea javanica oil-loaded liposomes (BJOL) on human hepatocellular cancer cell line HepG2. The related molecular mechanisms were determined.

Material and methods

Morphologic changes of HepG2 cells were observed by transmission electron microscope after treatment with BJOL in vitro. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after cell treatment with different doses of BJOL. Flow cytometry was performed. Nude mice were divided into 4 groups randomly and treated with different doses of BJOL. The apoptosis hepatocellular carcinoma was detected by TUNEL.

Results

Proliferation of HepG2 was inhibited significantly by BJOL in a dose-dependent manner (2.5 mg/l or 5 mg/l). Compared with the animal models treated with the negative control, the animal models in the BJOL group had higher weight and lower metastasis rates (p < 0.01). The rate of apoptosis in hepatocellular carcinoma tissue of the BJOL groups was increased when compared with the control group (p < 0.05).

Conclusions

Brucea javanica oil-loaded liposomes inhibits proliferation of HepG2. The effect appears to be dose-dependent, possibly by inducing apoptosis of cancer cells.     

A new triterpenoid from <Emphasis Type="Italic">Brucea javanica</Emphasis>

A new triterpenoid, bruceajavanin C (1), together with bruceosides A and B (2 and 3), bruceines D and E (4 and 5), yadanziosides A and G (6 and 7), (20R)-O-(3)-α-L-arabinopyranosylpregn-5-ene-3β,20-diol (8), and α-D-glucopyranoside, (3β, 20R)-3-hydroxypregn-5-en-20-yl (9) were isolated from the aerial parts of Brucea javanica. The structure of 1 was elucidated on the basis of 2D-NMR spectroscopic analysis. In addition, compounds 1, 3, 4, 5, and 6 exhibited mild inhibitory effect on NO production in LPS-stimulated RAW264.7 cells.     

Inhibitory effects of Ixora javanica extract on skin chemical carcinogenesis in mice and its antitumour activity.

Topical application of 100 mg/kg body weight of Ixora javanica flower extract inhibited the growth and delayed the onset of papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil. The extract at the same dose, when administered orally inhibited the growth of subcutaneously injected 20-methylcholanthrene (MCA)-induced soft tissue fibrosarcomas significantly. Oral administration of 200 mg/kg of the extract inhibited the growth of intraperitoneally transplanted sarcoma-180 and Ehrlich ascites carcinoma tumours besides showing an increase in the life span of the treated mice. Toxicity studies showed that the blood urea nitrogen levels were elevated post treatment. The active compounds responsible for the above inhibitory effects on tumour growth were identified as ferulic acid (4-hydroxy-3-methoxy cinnamic acid) and its regionmer 3-hydroxy-4-methoxy cinnamic acid.     

鸦胆子油治疗乳头状瘤远期疗效观察

中药鸦胆子别名苦参子,老鸦胆,为苦木科鸦胆子植物Brucea jauanica(L.)Merr,的果实,性味苦寒,杀虫,止痢,止疟,外用除疣,鸡眼。我们从鸦胆子种子中提取鸦胆子油,治疗乳头状瘤71例,并进行临床远期疗效观察,无一例复发,取得满意效果,现将制剂和临床治疗介绍如下: