������������������ϸ�۵�ҩ��ѧ�о�

??OBJECTIVE To study the pharmacokinetics of hot-melt spray-dried andrographolide granules and compare it with andrographolide bulk drug. METHODS A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the concentration of andrographolide in plasma of rats which were respectively given micronized andrographolide and hot-melt spray-dried andrographolide granules, then the pharmacokinetic parameters were calculated. RESULTS The pharmacokinetic parameters of andrographolide after a single dose administration of micronized andrographolide and hot-melt andrographolide were as following: t_1/2 were (347.33??9.32) and (390.82??8.78) min, t_max were (30.00??5.94) and (60.00??3.48) min, ??_max were (1 940.14??21.21) and (1 818.22??23.64) ng??mL^-1, AUC_0-t were (427 515.71??37 350.03) and (426 406.31??20 577.75) ng??min??mL^-1, AUC_0-inf were (545 423.14??47 969.18) and (593 569.87??30 247.35) ng??min??mL^-1, Vz/F were (43.48??4.75) and (44.96??3.81) kg??L^-1, CL/F were (86.78??3.35) and (79.74??2.89) kg??L^-1??min^-1, respectively. CONCLUSION Compared with the bulk drug, the hot-melt spray-dried andrographolide granules have a longer t_1/2, lower ??_max and delayed t_max in rats.     

�������ӻ�ѧ�ɷ��о�

??OBJECTIVE To investigate the chemical constituents of the seeds of Lepidium apetalum Willd. METHODS The compounds were isolated and purified by Diaion HP-20, Toyopearl HW-40, MCI Gel CHP-20, ODS, silica gel chromatography combined with Pre-HPLC and the structures were identified on the basis of spectral data and physiochemical properties. RESULTS Sixteen compounds were isolated and identified from the water extract as catechol(1), protocatechuic aldehyde(2), 2-phenyl acetamide(3), methyl- 5-hydroxypyridine-2-carboxlate(4), benzylcarbamic acid(5), N-benzylacetamide(6), raphanuside C(7), 1-phenyl-1,2-ethanediol(8), 2-(4-hydroxyphenyl)-ethanol(9), isorhamnetin-7-O-??-L-rhamnopyranoside(10), kaempferol(11), methyl 2,4,6-trihydroxybenzoate(12), 2-(4-hydroxyphenyl)acetonitrile(13), syringic acid(14), protocatechuic acid(15), and methyl sinapate(16). CONCLUSION Compounds 1-16 are isolated from this plant for the first time.     

����������Ƹ��ƾ����ڸ�Ů����������Ч�������о�

??OBJECTIVE To evaluate the effects of hormone replacement therapy(HRT) on the quality of life in climacteric women.METHODS The 202 patients were collected and divided into three groups according to whether or not they were treated with HRT: group 1 (not HRT), group 2 (HRT for the first time), group 3 (HRT for more than one year). All patients received follow-up visiting once per three months for one year. They were evaluated by the professionals through Kupperman index(KI), menopause-specific quality of life questionnaire(MENQOL), self-rating anxiety scale(SAS), self-rating depression scale(SDS). All patients were guided to improve the way of life.RESULTS After a year, KI, MENQOL and SAS in the three groups were improved significantly (P=0.003, 0.007, 0.014). KI and MENQOL were improved earlier than SAS. SDS was improved but not significantly(P=0.109). KI, MENQOL, SAS and SDS of patients in group 1 were improved significantly, but improved more weakly than those in group 2 and group 3. There is negative correlation between HRT and the values of every scale, and there is positive correlation between culture degree and SAS, SDS score values. CONCLUSION HRT canim prove the quality of life in climacteric women. The improvement in physical symptoms is earlier than that in mental symptoms. Anxiety and depression are more likely to occur in menopausal patients with high degree of education. Traditional Chinese medicine, exercise therapy and physical rehabilitation can be used as an auxiliary treatment for patients who are unable or unwilling to accept the HRT.     

���μ���ע���ü׻���������ͪ���й�����־Ը���е�ҩ��ѧ�о�

??OBJECTIVE To evaluate the pharmacokinetics characteristics and safety of antipsytrotic ziprasidone mesylate with single dose intramuscularly injected in healthy volunteers. METHODS A total of 12 healthy Chinese volunteers(male 6 cases and female 6 cases) were received intramuscularly single dose of ziprasidone mesylate, the dosage was 10 mg.Blood samples were collected at different time after intramuscularly injection.The concentrations of ziprasidone in serum were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated. RESULTS The concentration-time curves of ziprasidone fitted to two-compartment model.The pharmacokinetic parameters were stated as follows, ??_max was (97.85?? 29.24) ng??mL^-1;t_max was (0.56??0.30)h;MRT was (5.35??0.96) h; t_1/2 was (4.29??0.88)h; AUC_0??t was (405.6??98.68) ng??h??mL^-1,AUC_0???? was (413.3?? 100.69)ng??h??mL^-1; CL was (25.50??6.10)L??h^-1; Vd was (157.48??47.60)L; Kel was (0.168??0.035)h. There were no significant differences of the parameters between the male and female subjects. The common adverse events were somnolence, nausea and weakness with the severity of mild to moderate. CONCLUSION The pharmacokinetic parameters in 12 healthy volunteers after intramuscular injection of 10 mg ziprasidone mesylate are in line with that reported in the literature. This medicine has effect of sedation, so that it could be used to control the excited agitation.     

��������֬�����´���β���֢����ģ���о�

??OBJECTIVE To establish dose-related lung inflammatory injury in rats model with intratracheal atomization of lipopolysaccharide (lipopolysaccharides, LPS). METHODS Four groups of 4 rats were subjected to solvent or a single dose of LPS by intratracheal route using a IA-1B-2 inches-microsprayer. The male rats received 200 ??L solvent (control), LPS solutions (15, 5, 0.5 mg??kg^-1). All rats were sacrificed 24 h after dose administration, biochemical analysis and cell counts on bronchoalveolar lavage fluid (BALF) were performed on each rat. Lung, trachea and kidney were examined histologically. Serum chemistry profiles of creatinine, ALB, Na, K, Cl^- were detected. RESULTS Cell counts in BALF showed LPS groups had different degrees of inflammatory reaction. The alkaline phosphatase and total protein concentration were higher in LPS high dose group compared with other groups. In addition, the concentration of TNF-?? increased consistently with LPS dose and has statistical significance compared with the control group. Histopathology findings demonstrated that LPS produced an accumulation of foamy macrophages in the lungs and high degree of inflammation. CONCLUSION The results recommends intratracheally atomizing doses of LPS in rats model produced ranks of lung inflammatory injury.     

����ITS2���е�ҩ�øʲ���Ե��ϵ�����о�

??OBJECTIVE To obtain the genetic information of 181 domestic and foreign licorice samples by determining the internal transcribed spacer sequence 2 (ITS2) in order to clarify their phylogenetic relationships and differentiate the medicinal licorice species from the non-medicinal ones. METHODS Genomic DNA was first extracted from licorice samples of different origins and habitats. Then, the ITS2 sequences were amplified using PCR technique. Next, the ITS2 sequences were subjected to sequence analyses and neighbor-joining(NJ) tree analysis. Finally, the analytical method based on ITS2 DNA barcodes was established for the licorice species discrimination. The method was then applied to the phylogenetic analysis among the suspected domestic mutants, foreign licorice samples and domestic medicinal licorices, in addition to the discriminations of the medicinal and non-medicinal licorices. RESULTS The medicinal licorice could be explicitly separated from the two commonly encountered non-medicinal licorice species either by using ITS2 sequence analysis or NJ tree analysis; and the suspected domestic mutants and foreign licorice samples converged with the medicinal licorice to form one monophyletic branch in the NJ tree analysis, which indicated unambiguously conspecifics. CONCLUSION This study establishes a method for discrimination of medicinal and non-medicinal licorices based on ITS2 barcodes; and by the advantage of this method, the conspecific relationships among the suspected domestic mutants, foreign licorice samples and Chinese medicinal licorice are clarified. Thus a theoretical reference to the expansion of medicinal licorice resources and assurance of the safety and efficacy of the clinical licorice medications are provided.     

����ע��Һ��˳�����´��������Եı��������о�

??OBJECTIVE To investigate the protective effects of aidi injection on cisplatin (CDDP)-induced acute nephrotoxicity in rats. METHODS Forty male Sprague-Dawley rats were randomly divided into 5 groups, including the control group, CDDP group, the low, medium and high dose Aidi injection group (5, 10, 15 mL??kg^-1). Except the rats in control group, the rats of other groups were injected with CDDP on the third day. Aidi injection groups were administered to the rats once daily for 7 consecutive days. The control and CDDP groups were given corresponding regime of saline. On the eighth day, determine the content of serum creatinine (Scr) and blood urea nitrogen (BUN) in the rat, detect the level of superoxide dismutase (SOD), glutathione reductase (GSH-Px) and malondialdehyde (MDA) in the kidney tissue; observe HE staining slices of rats and find the renal pathological changes. RESULTS Compared with control group, the levels of Scr, BUN and MDA content were increased significantly in CDDP group, whereas the contents of SOD and GSH-Px were decreased significantly. There were serious, renal tubular epithelial cell apoptosis and inflammation in the kidney tissue. Kidney histopathology indicated that Aidi injection alleviated CDDP-induced tissue damage. The levels of Scr, BUN were decreased significantly in the low dose Aidi injection group, whereas the activity of SOD and GSH-Px were increased significantly. The medium dose of Aidi injection could increase the level of SOD and GSH-Px. The high dose of Aidi injection could enhance the activity of GSH-Px, without statistically significant effect on other indicators. CONCLUSION The RESULTS indicate that the low and middle dose of Aidi injection might protect the renal tissue from nephrotoxicity induced by cisplatin through anti-oxidation.     

��ͬ�����Ʊ���Ⱥ��ƽ�����ɢ������ʱȽ��о�

??OBJECTIVE To compare the properties of nitrendipine/PVP k25 solid dispersions prepared by three different technologies including spray drying, freeze-drying and co-precipitation technology. METHODS The characteristics of nitrendipine solid dispersions including micromorphology, crystalline profile and intermolecular interactions were analyzed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The dissolution and solubility characteristics were investigated by dissolution apparatus and constant temperature shaker. The crystallization inhibition effect of polymers against the drug in a supersaturated state was investigated by supersaturation crystallization experiment. RESULTS Nitrendipine existed in an amorphous form in the solid dispersion obtained by spray drying method. Compared with co-precipitation and freeze-drying method, the solid dispersion prepared by spray drying method significantly improved the dissolution and solubility of nitrendipine (P<0.05). The RESULTS of supersaturation crystallization inhibition test showed that PVP k25 could obviously inhibit the crystallization of nitrendipine in supersaturated state. CONCLUSION Based on the analysis of the above mentioned properties, nitrendipine solid dispersion prepared by spray drying technology displays the most optimal properties. Spray drying technology is more suitable for the practical production and industrial applications of nitrendipine solid dispersions.     

ҩƷ�ٴ���ֵ����ָ����ϵ�Ĺ����о�

??OBJECTIVE To analyze the connotation and composition of the clinical value of drugs, and to build the index system for the evaluation of drug's clinical value, hence to provide references for its scientific evaluation. METHODS We designed the preliminary constructs index system referencingmedicine clinical evaluation indicatorsof German and French firstly. And then the expert interview and Delphi survey were used to analysis to determine the index system and index weight of medicine clinical evaluation. RESULTS The classified index system of the clinical value was established, which was composed of 2 first-grade indexes including clinical value and innovation value and 15 grade two indexes. Experts were invited to assess the value ranking according to the background information of rosuvastatin, atorvastatin and simvastatin statin drugs by their generic names. The expert's scoring results were summarized to determine the sequence. And it were compared with the average market prices in Germany, France, Britain, the United States, South Korea, Japan and analyzed. CONCLUSION The clinical value of drugs is an international standard for determining the reasonable price of drugs. This research method is feasible to determine the drug prices sequencing by the classified clinical value of drugs in the same kind of product. The price sequencing of some generic names of statin drugs did not correspond with its clinical value sequence, and the price can not reflect its value. The integrity and authenticity of the background data directly determine the classification of the clinical value. Various parties are needed to participate in providing detailed data and information.     

阿霉素高聚物胶束的制备及其体外抗肿瘤活性研究

 目的制备阿霉素高聚物胶束并研究其体外抗肿瘤活性。方法以N-正辛基-N′-琥珀酰基壳聚糖为载体,采用透析法制备阿霉素胶束,并测定其载药量、包封率、形态、粒径、表面电位(Zeta电位),及其对K562,HepG2肿瘤细胞的细胞毒作用。结果阿霉素高聚物胶束载药量为35.8%,包封率为75.3%,粒径控制在100～200nm,药物体外释放较缓慢,对K562肿瘤细胞及HepG2细胞的细胞毒作用优于阿霉素。结论N-正辛基-N′-琥珀酰基壳聚糖不仅是阿霉素的优良载体,且可提高抗K562,HepG2肿瘤细胞的活性。     

白花蛇舌草的免疫学调节活性和抗肿瘤活性

目的：研究白花蛇舌草的免疫学调节活性和抗肿瘤活性。方法：用^3H介入法分析了白花蛇舌草提取物（Oldenlandia diffusa extract,ODE）对小鼠脾细胞的增殖活性；用^51Cr游离实验测定了小鼠和人杀伤细胞对肿瘤细胞的特异性杀伤活性，用ELISA法和生物法研究了B细胞抗体的以及单核细胞的细胞因子产生，并用^3H介入法分析了单核细胞对肿瘤细胞的吞噬功能；用层析法、蛋白酶消化法和糖分解处理（即NaIO4处理）分析了白花舌草的化学成分。结果：ODE对小鼠脾细胞的增殖活性有很强的促进作用；ODE增强小鼠和人杀伤细胞对肿瘤细胞的特异性杀伤活性，增强B细胞抗体的产生以及单核细胞的细胞因子产生，并增强单核细胞对肿瘤细胞的吞噬功能，白花蛇舌草的化学成分为90道尔顿的糖蛋白。结论：ODE对小鼠的人有免疫调节作用，并通过刺激机体的免疫系统杀伤或蚕噬肿瘤细胞，这些活性可应用于临床调节免疫功能和治疗肿瘤等疾病。     

冬凌草甲素/胆固醇甲酰-壳聚糖共聚物纳米胶束的制备及其体外抗肿瘤作用

 目的 制备冬凌草甲素/胆固醇甲酰-壳聚糖共聚物（ORI/CF-CS）纳米胶束并研究其体外抗肿瘤活性。方法 采用酰胺化反应合成胆固醇甲酰-壳聚糖共聚物（CF-CS）;以CF-CS为载体材料制备ORI/CF-CS纳米胶束,并测定其载药量、包封率、形态、粒径和ξ电位;MTT法测定其对宫颈癌Hela肿瘤细胞的细胞毒作用。结果 ORI/CF-CS纳米胶束载药量为9.16%,包封率为48.83%,粒径控制在68.10~113.8 nm内,ξ电位为-34.97~-29.19 mV,体外释药缓慢;ORI/CF-CS纳米胶束对Hela肿瘤细胞的细胞毒作用优于冬凌草甲素溶液,且IC₅₀ 值比冬凌草甲素溶液低约3倍。结论 CF-CS是冬凌草甲素的优良载体,且可提高其抗Hela肿瘤细胞的活性。     

生脉散加黄芪对LAK细胞抗肿瘤活性的正向调节作用

本文用~3H释放方法检测了生脉散加黄芪对LAK细胞活性的影响。43例LAK细胞分别对8例不同型别患者的新鲜急性白血病细胞表现了明显的杀伤活性。以最适浓度(100μg/ml)生脉散加黄芪制剂协同IL-2诱生LAK细胞,其活性明显增强。最适浓度(10μg/ml)的人参总皂甙制剂作用稍强于生脉散加黄芪制剂。     

肝动脉栓塞用吡柔比星-碘油微乳的组方筛选及细胞毒作用评价

 目的 研制肝动脉栓塞用吡柔比星-碘油微乳并对其体外抗肿瘤活性进行研究。 方法 采用伪三元相图法研究不同表面活性剂、助表面活性剂和K_m值形成微乳的能力及区域,优选微乳处方,制备吡柔比星-碘油微乳,并对微乳的物理性质、稳定性进行研究;采用MTT法对吡柔比星-碘油微乳体外抗肿瘤活性进行考察。结果 碘化油/大豆磷脂/无水乙醇/水形成的微乳粒径小、黏度低,初步稳定性实验表明,4 ℃下放置药物含量和粒径均无显著变化。MTT实验结果表明,吡柔比星-碘油微乳对人肝癌细胞有明显抑制作用,空白微乳对肝癌细胞HepG-2抑制作用弱。结论 吡柔比星-碘油微乳制备简单,工艺重复性良好,质量稳定,体外抗肿瘤活性较强,为肝动脉栓塞给药剂型的改进提供了依据。     

洛莫司汀热敏脂质体的制备及体外抗肿瘤活性研究

 目的制备洛莫司汀热敏脂质体并考察其体外抗肿瘤活性。方法以二棕榈酰-D,L-α磷脂酰胆碱(DPPC)和胆固醇为载体,采用薄膜分散法制备洛莫司汀热敏脂质体,以甘露醇为赋形剂将其制成冻干脂质体;透射电镜观察冻干前后脂质体的形态,激光散射法测定脂质体的粒径分布及Zeta电位;Sephadex G-50柱分离脂质体与未包封药物,HPLC测定脂质体包封率;并考察脂质体的体外释药特性和体外抗肿瘤活性。结果脂质体为多层圆形或椭圆型小囊,无粘连,大小均匀,冷冻干燥前后平均粒径分别为189.8和274.9 nm;ζ电位分别为-19.13和-0.83 mV,包封率分别为68.28%和60.32%(n=3)。在pH7.4 PBS介质、相变温度42℃时30 min累积释药88.64%。相同剂量洛莫司汀溶液与洛莫司汀热敏脂质体比较,37℃时肿瘤抑制率分别为33.04%和35.35%,两者无明显差异(P>0.05);加热到42℃时肿瘤抑制率明显增加,加热10 min肿瘤抑制率分别为36.75%和58.87%;加热30 min肿瘤抑制率分别为50.52%和71.69%。结论洛莫司汀热敏脂质体在相变温度时,体外释药明显增加,体外抑瘤效果明显提高。     

红豆杉细胞提取物对癌细胞的抑制作用研究

目的：了解红豆杉细胞提取物对肝癌细胞系SMMC—7721生长的影响。方法：运用MTT比色法测定癌细胞的存活率和流式细胞仪分析细胞周期。结果：红豆杉细胞二氯甲烷提取物对癌细胞SMMC—7721的抑制作用远大于甲醇提取物，IC50值分别为0．0834mgDCWW．m1^-1和0．8002mgDCW．m1^-1；流式细胞仪分析发现外加红豆杉细胞二氯甲烷提取物后肝癌细胞G2／M期含量增加。结论：红豆杉细胞提取物在体外对肝癌细胞SMMC—7721的生长通过诱导凋亡而具有抑制作用。     

叶酸靶向紫杉醇聚合物纳米囊泡的制备及其抗肿瘤活性研究

 目的 制备新型叶酸靶向紫杉醇聚合物纳米囊泡,研究其理化性质、细胞毒性和体内抗肿瘤活性。方法 以两亲性三嵌段共聚物聚己内酯-b-聚乙二醇-b-聚己内酯（PCL-b-PEG-b-PCL）、甲氧基聚乙二醇二硬脂酰磷脂酰乙醇胺（mPEG2000-DSPE）、偶联叶酸的磷脂DSPE-PEG(2000) Folate共混物为载体材料,通过薄膜-超声分散法制备出叶酸靶向紫杉醇聚合物纳米囊泡并对其进行形态、粒径及其分布、Zeta电位、载药量及包封率、体外释放等表征,用CCK-8法研究了聚合物纳米囊泡对H1299肺癌细胞的细胞毒性,并评价其在BALB/c小鼠EMT-6乳腺癌模型中的抗肿瘤效果。结果 叶酸靶向紫杉醇聚合物纳米囊泡呈球形,具有明显的核-壳结构,粒径均匀。随着紫杉醇投药量的增加,纳米囊泡的粒径增大,包封率降低。载药30%的叶酸靶向紫杉醇聚合物纳米囊泡的平均粒径为311 nm,多分散系数为0.171,Zeta电位为-30.3 mV,包封率为91.16%。体外释放研究表明,载紫杉醇聚合物纳米囊泡基本无药物突释现象,具有缓释特性。细胞毒性研究表明,当紫杉醇浓度为25 μg·mL-1时,叶酸靶向紫杉醇聚合物纳米囊泡的细胞毒性低于相应浓度的紫杉醇/聚氧乙烯蓖麻油注射剂。体内抗肿瘤活性实验研究表明,叶酸靶向紫杉醇聚合物纳米囊泡对小鼠EMT-6乳腺癌具有明显抑制作用,具有与紫杉醇/聚氧乙烯蓖麻油注射剂相似的抑制肿瘤作用。结论 叶酸靶向紫杉醇聚合物纳米囊泡具有高载药量及包封率、均匀的粒径及分布、缓释特性、低毒和较好的抗肿瘤作用,是一种有潜力的紫杉醇缓控释新剂型用于提高紫杉醇的药效并且降低不良反应。     

噻唑蓝法测定抗肿瘤复方制剂仙慈丹的体外抗肿瘤活性

 目的 分离筛选出抗肿瘤复方制剂仙慈丹（XCD）的抗肿瘤活性部位。方法 采用大孔树脂柱色谱法对抗肿瘤复方制剂XCD水提取液进行分段富集,运用噻唑蓝（MTT）比色法对分段富集得到的部位进行体外抗肿瘤活性测定。结果 抗肿瘤复方制剂XCD水提取液过AB-8型树脂纯化得到的P2（体积分数20%乙醇洗脱液）、P3（体积分数40%乙醇洗脱液）、P4（体积分数60%乙醇洗脱液）、P5（体积分数80%乙醇洗脱液）对人肝癌HepG2细胞表现出较强的抑制作用。结论 XCD水提液过大孔树脂后乙醇洗脱部位是XCD制剂的抗肿瘤活性部位。     

胸腺五肽pH-敏感壳聚糖纳米粒的制备、体外释放及生物活性

 目的为了提高胸腺五肽口服的稳定性及生物利用度,制备胸腺五肽pH-敏感壳聚糖纳米粒并考察其理化性质、体外释放及生物活性。方法采用离子胶凝法制备胸腺五肽壳聚糖纳米粒并用Eudragit S100包衣制备pH-敏感纳米粒;透射电镜和环境扫描电镜观察纳米粒形态;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;动态透析法研究载药纳米粒的体外释放特性;模拟人工消化液考察纳米粒中胸腺五肽的生物稳定性;淋巴细胞增殖反应评价制剂的生物活性。结果pH-敏感胸腺五肽壳聚糖纳米粒的平均粒径为(175.6±17)nm,Zeta电位为(28.44±0.5)mV,包封率为(76.70±2.6)%。胸腺五肽pH-敏感壳聚糖纳米粒具有良好的pH依赖性:在0.1 mol·L^-1HCl溶液中累积释放24.65%,在pH5.0 PBS溶液中累积释放41.01%,在pH7.4 PBS溶液中累积释放81.44%。pH敏感壳聚糖纳米粒制剂中的胸腺五肽在人工胃液中稳定,在人工肠液中半衰期为15 min。淋巴细胞体外转化实验表明,胸腺五肽pH-敏感壳聚糖纳米粒保留了TP5的生物活性并且具有浓度依赖性。结论pH-敏感壳聚糖纳米粒可能是口服胸腺五肽的良好载体。