复方地西泮鼻腔给药的安全性评价

目的:考察地西泮与薄荷醇配伍鼻腔给药的鼻黏膜毒性,探讨地西泮鼻腔给药的可行性.方法:以家兔鼻黏膜为研究对象,考察地西泮单用、地西泮与薄荷醇伍用给药1周和停药1周后,对家兔鼻黏膜细胞形态结构的影响及恢复情况.结果:病理组织切片显示,地西泮单用组和地西泮与薄荷醇伍用组鼻腔给药1周后,大鼠鼻黏膜细胞上皮层厚度无明显改变.停药1周后,光学显微镜观察鼻黏膜损伤的情况有所恢复.结论:地西泮单独鼻腔给药、薄荷醇单独鼻腔给药、地西泮和薄荷醇配伍鼻腔给药后,对黏膜的毒性轻微且毒性具有可逆性.     

眼镜蛇神经毒素鼻黏膜透过性的研究

目的探讨眼镜蛇神经毒素(-αcobrotoxin,或Nt)对不同动物鼻黏膜透过性及冰片的促渗作用。方法采用体外渗透鼻黏膜实验、在体渗透鼻黏膜重循环实验等方法,将125I-Nt对几种不同动物鼻黏膜的透过性进行了比较,考察不同动物鼻黏膜的透过性及冰片对其透过性的影响。结果Nt能透过鼻黏膜而吸收,且在冰片作用下吸收明显增加。结论冰片能促进Nt的吸收,Nt可用于鼻腔给药。     

单向灌流法研究磷酸川芎嗪的大鼠在体肠吸收

目的研究磷酸川芎嗪的大鼠在体肠吸收性质。方法运用单向灌流模型、采用HPLC法对药物的质量浓度进行检测,分别研究灌流速度、药物质量浓度、pH值以及吸收部位对磷酸川芎嗪吸收的影响。结果灌流速度和pH值对磷酸川芎嗪的吸收速率常数(ka)和表观吸收系数(Papp)有显著性影响;药物质量浓度对ka和Papp无显著性影响;小肠各段间药物吸收的ka和Papp无显著性差异,但与回肠段相比吸收明显增大。结论磷酸川芎嗪的吸收速率不受药物质量浓度的影响,而与灌流速度、灌流液的pH值和肠段部位有关。药物在全肠道吸收较好,吸收窗主要在小肠,且小肠内无明显的特定吸收部位。     

川芎嗪的鼻腔吸收及冰片的促进作用

目的 :探讨川芎嗪的鼻腔吸收及冰片的促进作用。方法 :采用大鼠在体鼻腔重循环法 ,研究川芎嗪鼻腔吸收的量效关系及冰片对其鼻腔吸收的影响。结果 :循环液中川芎嗪的浓度在 0 .2 5 ,0 .75 ,1.2 5g·L- 1时 ,鼻腔的吸收速率常数分别为 0 .0 195、0 .0 2 2 7、0 .0 2 4 1min- 1;但当药液浓度为 2 .5 ,5 .0g·L- 1时 ,鼻粘膜吸收速率常数随川芎嗪浓度的增加反而减少。结论 :川芎嗪可通过鼻腔吸收 ,冰片对其鼻腔吸收具有促进作用。     

胸腹水LDH和与血清LDH比值及TP测定的临床鉴别诊断价值

目的:探讨胸腹水中的乳酸脱氢酶(LDH)和胸腹水中的LDH与血清LDH的比值及总蛋白(TP)测定的临床鉴别诊断意义.方法:分别采用乳酸法和双缩脲比色法检测73例患者不同性质胸腹水中的LDH和与血清LDH比值及TP的浓度,并对检测数据进行统计分析.结果:恶性肿瘤组和结核性胸膜炎组标本胸腹水LDH差异无显著性(P＞0.05),但均高于慢性非特异性炎症组(P＜0.05);恶性肿瘤组和慢性非特异性炎症组的胸腹水LDH与血清LDH比值差异无显著性(P＞0.05),但均高于结核性胸膜炎组(P＜0.05);恶性肿瘤组和结核性胸膜炎组标本TP差异无显著性(P＞0.05),但均高于慢性非特异性炎症组(P＜0.05).结论:联合检测胸腹水LDH和胸腹水LDH与血清LDH比值及TP对胸腹水的鉴别诊断有重要的临床参考价值.     

氢溴酸高乌甲素鼻用原位凝胶剂的制备及其处方评价

目的：制备氢溴酸高乌甲素（LH）鼻用原位凝胶剂,并进行处方考察以提高其鼻腔给药的镇痛效果。方法：采用在体蟾蜍上腭纤毛法考察不同LH处方对鼻黏膜纤毛的毒性、大鼠在体鼻腔循环实验考察处方中3种吸收促进剂（β-环糊精、吐温-80和冰片）对LH的鼻黏膜吸收的促进作用以及小鼠扭体法实验考察不同LH处方的镇痛药效,从而确定LH鼻用原位凝胶剂的最佳处方工艺。结果：处方中LH和所选用的辅料对鼻黏膜纤毛均无显著毒性;3种吸收促进剂对LH的鼻黏膜吸收速率常数无显著影响（P〉0．05）;在所有受试处方中,结冷胶和β-环糊精联用处方制剂的镇痛效果最佳,其药效与腹腔注射相同剂量的LH注射液无显著差异（P〉0．05）。结论：结冷胶和β-环糊精联用是制备LH鼻用原位凝胶剂的最佳处方组合。     

离体心肌组织灌流在评价药源性QT间期延长中的应用及影响因素

鼻黏膜给药制剂是药物制剂领域的研究热点之一,但鼻腔给药可能会对鼻黏膜造成损害,因此应重视该类制剂对鼻黏膜毒性的考察。本文综述了鼻黏膜给药制剂的局部毒性评价方法,包括鼻纤毛毒性评价、鼻黏膜形态学评价、红细胞溶血实验及生化物质释放。不同评价方法各具优缺点,在对鼻腔给药制剂进行评价时,要根据研究内容与目的合理地选择评价方法。     

胸腹水LDH和与血清LDH比值及TP测定的临床鉴别诊断价值

目的:探讨胸腹水中的乳酸脱氢酶(LDH)和胸腹水中的LDH与血清LDH的比值及总蛋白(TP)测定的临床鉴别诊断意义.方法:分别采用乳酸法和双缩脲比色法检测73例患者不同性质胸腹水中的LDH和与血清LDH比值及TP的浓度,并对检测数据进行统计分析.结果:恶性肿瘤组和结核性胸膜炎组标本胸腹水LDH差异无显著性(P＞0.05),但均高于慢性非特异性炎症组(P＜0.05);恶性肿瘤组和慢性非特异性炎症组的胸腹水LDH与血清LDH比值差异无显著性(P＞0.05),但均高于结核性胸膜炎组(P＜0.05);恶性肿瘤组和结核性胸膜炎组标本TP差异无显著性(P＞0.05),但均高于慢性非特异性炎症组(P＜0.05).结论:联合检测胸腹水LDH和胸腹水LDH与血清LDH比值及TP对胸腹水的鉴别诊断有重要的临床参考价值.     

抗动脉粥样硬化基因疫苗经鼻腔免疫黏膜毒性的初步评价

目的:考察抗动脉粥样硬化基因疫苗经鼻腔接种免疫的黏膜毒性.方法:以壳聚糖为基因载体,制备载基因疫苗的壳聚糖纳米粒.对高脂家兔模型滴鼻免疫6次,28周时取鼻黏膜及肺部组织行组织病理学检查,扫描电镜观察鼻黏膜纤毛的超微结构变化.结果:基因疫苗经鼻腔免疫可以显著诱导抗体,延缓动脉粥样硬化的发展.组织病理学检查表明,鼻黏膜及肺部组织形态正常.黏膜纤毛超微结构的扫描电镜观察表明,鼻黏膜纤毛排列有序,无断裂、脱落、倒伏等异常现象.结论:基因疫苗经鼻腔接种未致黏膜及纤毛损伤,鼻腔给药有潜力发展为一种新的接种途径.     

冰片对川芎嗪血药浓度和在脑中分布的影响

目的：探讨冰片对川芎嗪血药浓度和在脑中分布的影响。方法：经股静脉单用或复合冰片给予大鼠川芎嗪10mg／kg，采用高效液相色谱法测定不同时间的血浆和脑组织中川芎嗪药物浓度。结果：川芎嗪复合冰片后，血浆药物浓度发生明显变化，在所观察的时间里，血浆药物浓度比单用川芎嗪低；但川芎嗪复合冰片后能提高川芎嗪在脑组织中的含量。结论：冰片可促进川芎嗪在脑中的分布，川芎嗪复合冰片治疗脑血管疾病时临床显效可能更快。     

磷酸川芎嗪气雾剂急性毒性及局部刺激性试验研究

目的观察磷酸川芎嗪气雾剂的急性毒性、黏膜刺激性。方法采用最大给药量试验观察鼻腔及腹腔给药后SD大白鼠短期内出现的急性毒性反应及其程度。观察一般情况与解剖显微镜下检查呼吸道黏膜局部刺激性反应。结果鼻腔及腹腔给药后SD大鼠的最大给药量为1%磷酸川芎嗪气雾剂1 mL,短期内未出现急性毒性反应及死亡情况;局部刺激性试验中大鼠一般情况良好,未发生毒副反应,显微镜下观察鼻、喉、气管等呼吸道黏膜未见损伤性变化。结论磷酸川芎嗪气雾剂鼻腔用药无明显毒性及刺激性,可供临床使用。     

吸收促进剂对人参皂苷Rg1鼻腔吸收的促进作用及鼻腔毒性

目的考察吸收促进剂对人参皂苷Rg1鼻腔黏膜的吸收促进作用以及对鼻腔黏膜毒性。方法采用大鼠在体鼻腔循环考察人参皂苷Rg1鼻腔吸收及吸收促进剂的促吸收作用，在体蟾蜍上腭纤毛法评价药物对纤毛运动的影响；考察吸收促进剂对家兔血红细胞的溶血作用、对鼻腔循环液中总蛋白和乳酸脱氢酶的影响及对鼻腔黏膜形态学的影响。结果人参皂苷Rg1鼻腔吸收必须加入吸收促进剂。各种吸收促进剂的促进作用为：1%去氧胆酸钠作用显著；1%甘草酸二钾和1%氮酮作用中等；1% Tween-80，2% β-环糊精、0.5%冰片、0.5%壳聚糖、5%羟丙-β-环糊精和0.1% EDTA等作用微弱。吸收促进剂对鼻腔黏膜毒性影响：1%去氧胆酸钠、1%氮酮和1%甘草酸二钾毒性大；1% Tween-80，2% β-环糊精及5%羟丙-β-环糊精等毒性中等；0.5%冰片、0.5%壳聚糖和0.1% EDTA毒性小。结论0.5%冰片与0.5%壳聚糖可安全有效地促进人参皂苷Rg1的鼻腔吸收。     

冰片滴鼻对豚鼠鼻粘膜血管和脑血管通透性的影响研究

目的:研究不同浓度冰片滴鼻后对豚鼠鼻粘膜血管和脑血管通透性的影响。方法:将豚鼠随机分为系列浓度冰片(0.5%、1.0%、2.0%)组、组胺组和液体石蜡组,滴鼻给药后静脉注射2%伊文思蓝(EB),10min后处死豚鼠,取鼻粘膜和脑组织,测定并计算鼻粘膜和脑组织中EB含量。结果:与液体石蜡组比较,系列浓度冰片组鼻粘膜和脑组织中EB含量更高(P<0.05或P<0.01),并以2.0%冰片组最为明显。结论:冰片滴鼻可以明显增加豚鼠鼻粘膜血管和脑血管的通透性。     

Ligustrazine is a vasodilator of human pulmonary and bronchial arteries

We have investigated the dilator effect of ligustrazine, the semisynthetic principle of a traditional Chinese herbal remedy, on human pulmonary and bronchial arteries in vitro. Ligustrazine caused a concentration-dependent relaxation of human small pulmonary arteries, which was independent of endothelium. Although ligustrazine was equally potent in inducing dilatation of pulmonary and bronchial arteries, it was about 10 times more potent in relaxing small pulmonary arteries (300-500 microns i.d.) compared with lobar pulmonary arteries (7-8 mm i.d.). By contrast, the relaxant responses of small and lobar pulmonary arteries to sodium nitroprusside was not significantly different. Ligustrazine was equally potent in relaxing prostaglandin F2 alpha- or 5-hydroxytryptamine-precontracted pulmonary arteries, suggesting that it is not a prostaglandin F2 alpha or 5-hydroxytryptamine antagonist. Preincubating the vessels with propranolol (1 microM) or indomethacin (10 microM) had no significant effect on the ligustrazine-induced vasodilatation. However, ligustrazine caused concentration-dependent inhibition of calcium-evoked contraction when applied to rat aorta in calcium-free K(+)-depolarizing medium. We conclude that ligustrazine is a dilator of human pulmonary and bronchial arteries, which is endothelium-independent and that ligustrazine preferentially relaxes pulmonary resistance vessels rather than large conduit pulmonary arteries.     

Ligustrazine inhibits lipopolysaccharide-induced proliferation by affecting P27, Bcl-2 expression in rat mesangial cells

Ligustrazine has a renoprotective effect against nephritis. In the present study, we investigated the roles of ligustrazine on lipopolysaccharide-induced changes of proliferation, cell cycle in cultured rat mesangial cells. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that rat mesangial cells treated with lipopolysaccharide (10mg/l) underwent significant proliferation compared with control group. This effect was significantly inhibited by ligustrazine (400 to 2500 mg/l). Flow cytometric analysis revealed that cells treated with lipopolysaccharide showed significant reduction in the ratio of G0/G1 phase and significant elevation in the ratio of S+G2/M phase. The changes of cell cycle induced by lipopolysaccharide were reversed by ligustrazine. In addition, lipopolysaccharide suppressed P27 protein expression was significantly increased by ligustrazine (100, 500, 2500 mg/l). Moreover, rat mesangial cells treated with lipopolysaccharide showed scanty apoptosis with up-regulation of Bcl-2expression, while Bax protein expression was not changed. Ligustrazine (100, 500, 2500 mg/l) significantly reversed lipopolysaccharide-induced up-regulation of Bcl-2 protein and increased apoptotic cell death. In summary, ligustrazine displayed a significant inhibiting effect on lipopolysaccharide-induced proliferation through increasing P27 and decreasing Bcl-2 protein expression in rat mesangial cells.     

Ligustrazine improves the compensative effect of Akt survival signaling to protect liver Kupffer cells in trauma-hemorrhagic shock rats

Trauma-hemorrhagic shock (THS) is a medical emergency that is encountered by physicians in the emergency department. Chuan Xiong is a traditional Chinese medicine and ligustrazine is a natural compound from it. Ligustrazine improves coronary blood flow and reduces cardiac ischemia in animals through Ca²⁺ and ATP-dependent vascular relaxation. It also decreases the platelets' bioactivity and reduces reactive oxygen species formation. We hypothesized that ligustrazine could protect liver by decreasing the inflammation response, protein production, and apoptosis in THS rats. Ligustrazine at doses of 100 and 1000 μg/mL was administrated in Kupffer cells isolated from THS rats. The protein expressions were detected via western blot. The THS showed increased inflammation response proteins, mitochondria-dependent apoptosis proteins, and had a compensation effect on the Akt pathway. After ligustrazine treatment, the hemorrhagic shock Kupffer cells decreased inflammatory response and mitochondria-dependent apoptosis and promoted a more compensative effect of the Akt pathway. It suggests ligustrazine reduces inflammation response and mitochondria-dependent apoptosis induced by THS in liver Kupffer cells and promotes more survival effects by elevating the Akt pathway. These findings demonstrate the beneficial effects of ligustrazine against THS-induced hepatic injury, and ligustrazine could be a potential medication to treat the liver injury caused by THS.     

The <Emphasis Type="Italic">in situ</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> study on enhancing effect of borneol in nasal absorption of Geniposide in rats

The objective of this research was to study the in situ and in vivo nasal absorption of Geniposide (Ge) co-administered with borneol. A rat in situ nasal perfusion technique with a novel volumeadjusted calculation was used to examine the absorption rate and extent of Ge. The influence of different experimental conditions such as purity of extract, drug concentration, co-administration with synthetic borneol or natural borneol were also investigated. Results indicated nasal absorption of Ge was primarily by passive diffusion that resembled first order kinetics. Following co-administration with borenol, the drug absorption was increased by 1.4 and 1.7 folds for natural borneol and synthetic borneol, respectively. However, the effect of other factors on drug absorption was not significant. In addition, it was also observed that there is a positive correlation between the absorption of water and Ge by the nasal route. In vivo studies carried out in rats where Ge was co-administered with NB and the pharmacokinetic profile obtained following intranasal administration were compared with those after intravenous administration. The bioavailability of Ge by intranasal was 101.5% and T_max was 2.04 ± 0.64 min. MRT was 218.7 ± 74.1 min and 44.4 ± 8.9 min for intranasal and intravenous, respectively. Combined with the borneol, Ge can be promptly and thoroughly absorbed intranasally in rats.     

川芎嗪、环丙沙星对体外培养的人结膜成纤维细胞增殖抑制作用的研究

目的 :探讨川芎嗪、环丙沙星对人结膜成纤维细胞增殖的抑制作用。方法 :应用噻唑蓝法 ,观察不同浓度川芎嗪、环丙沙星对人结膜成纤维细胞增殖的影响。结果 :川芎嗪、环丙沙星对人结膜成纤维细胞均有明显的抑制作用 ,并与浓度呈正比。结论 :川芎嗪、环丙沙星可有效防治增殖性玻璃体视网膜病变。     

Protective effects of ligustrazine on TNF-α-induced endothelial dysfunction

To investigate the effects of Ligustrazine, a compound derived from chuanxiong, on tumor necrosis factor-α (TNF-α) stimulated endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α in vitro. Nitric oxide (NO) was measured as a standard of endothelial dysfunction. Two important indicators of autoimmunity, intracellular adhesion molecular-1 (ICAM-1) and heat shock protein 60 (HSP60), were selected to evaluate the influence of Ligustrazine on HUVECs. Ligustrazine (40 μg/ml) significantly reversed the decrease in NO production induced by TNF-α (5 ng/ml) in HUVECs. The expressions of ICAM-1 and HSP60 were increased by TNF-α treatment, but dramatically inhibited by treatment with ligustrazine in TNF-α-stimulated cells. Ligustrazine increased the production of NO in HUVECs and had an immunomodulatory effect on HUVECs stimulated with TNF-α by down-regulating the expression of ICAM-1 and HSP60. These results suggest that ligustrazine protects the endothelium via inhibition of immunological reactions, preventing atherosclerosis.     

注射用盐酸川芎嗪细菌内毒素检查法的研究

目的 建立注射用盐酸川芎嗪细菌内毒素检查方法.方法 参照《中国药典》2010年版二部细菌内毒素检查法进行试验.结果 将注射用盐酸川芎嗪稀释至0.06 mg· mL-1时,对细菌内毒素和鲎试剂的反应无干扰作用.结论 该品种可采用细菌内毒素检查法控制药品质量,其内毒素限值为每1 mg盐酸川芎嗪中含内毒素的量应小于2.0 EU·mg-1.