新型选择性环氧合酶-2抑制剂的研究及临床应用

目的:对新型选择性环氧合酶-2抑制剂的研究及临床应用进行谈论分析。方法:将100只大鼠根据体重分为溶剂对照组、美洛昔康高剂量组、美洛昔康中剂量组、美洛昔康低剂量组及吡罗昔康对照组,对美洛昔康抗炎镇痛的效果进行讨论分析。结果:美洛昔康低剂量组、美洛昔康中剂量组、美洛昔康高剂量组、吡罗昔康对照组和溶液对照组在给药后1.5小时、3小时及6小时痛阀有明显的升高,数据差异具有统计学意义(P0.05)。结论:美洛昔康具有很好的抗炎镇痛效果。     

玻璃酸钠联合美洛昔康治疗类风湿性关节炎

目的观察玻璃酸钠(SH)联合美洛昔康治疗类风湿关节炎的疗效。方法将120例类风湿性关节炎患者随机分为SH组、美洛昔康组、SH+美洛昔康联合用药组,每组40例。SH组仅关节腔内注射SH;美洛昔康组仅服用美洛昔康;联合用药组关节腔内注射SH,并服用美洛昔康。美洛昔康口服7.5 mg/次,2次/d;SH关节腔内注入,2 mL/次,1次/周。对治疗前及治疗5周后结果进行比较。结果经5周治疗后,3组患者的临床指标和血沉均显著改善(P<0.05)。联合用药组的临床指标及血沉、CRP改善值均优于SH组和美洛昔康组(P<0.05)。联合用药组的疗效较SH组及美洛昔康组有显著性差异(P<0.05)。结论 SH联合美洛昔康治疗类风湿关节炎疗效明显优于单用美洛昔康和单用SH,且安全性较好。     

美洛昔康治疗骨关节炎的临床疗效

目的：评价美洛昔康治疗骨关节炎的疗效和安全。方法：120例骨关节炎患者随机分成2组，试验组60例，给予美洛昔康胶囊7．5mg，po，qd；对照组60例给予萘普生胶囊500mg，po，bid。疗程均为4wk。结果：美洛昔康胶囊和萘普生胶囊的有效率分别为85％和65％；药物不良反应发生率分别为11．3％和26．7％，但程度均比较轻微。结论：美洛昔康是治疗骨关节炎有效和比较安全的药物。     

美洛昔康β-环糊精包合物的研制

目的 增加难溶性药物美洛昔康的溶解度,为其进一步制成适宜剂型打下实验基础。方法 采用溶液-搅拌法制备美洛昔康β-环糊精包合物,并采用显微镜法和红外光谱法进行鉴定。结果 美洛昔康β-环糊精包合物包合成功。其包合优化工艺条件为X1=60℃;X2=1．2：1;X3=90min。美洛昔康β-环糊精包合物的溶解度是美洛昔康的15倍。结论 包合物可明显提高美洛昔康的溶解度。     

两种新的选择性环氧合酶-2抑制剂

选择性环氧合酶 2 (COX 2 )抑制剂已成为寻找副作用小的、非甾体类抗炎药的研究方向。美洛昔康与氯诺昔康是两种结构不同的昔康类非甾体抗炎药 ,所具有的消炎镇痛作用及良好的胃肠道耐受性与它们对COX 2的选择性抑制作用有关。本文报道了美洛昔康和氯诺昔康对COX 2的选择性抑制作用及相应的药效学和药动学性质。     

美洛昔康抗炎作用的实验研究

目的观察美洛昔康的抗炎作用。方法采用大鼠急性、亚急性及免疫性炎症模型,观察美洛昔康对角叉菜胶致大鼠足跖肿胀和大鼠棉球肉芽肿的影响以及美洛昔康对大鼠佐剂性关节炎的预防和治疗作用。结果美洛昔康对多种致炎剂引起的炎性水肿均具有明显的抑制作用,1.0和3.0mg     

美洛昔康合成工艺改进

目的改进关洛昔康的合成工艺，提高美洛昔康的收率。方法通过工业丙醇为原料合成2-氨基-5-甲基噻唑，提高了收率。美洛昔康的合成采用二甲基甲酰胺和二甲苯混合作溶剂，减少溶剂用量。结果收率从40．7％提高到52．5%。结论美洛昔康的改进工艺提高了工业化生产的批生产量。     

美洛昔康对人肝癌HepG_2细胞增殖的抑制作用

目的:研究环氧合酶(COX)-2抑制剂美洛昔康对肝癌细胞HepG2的生长抑制作用及其作用机制。方法:MTT法观察美洛昔康在不同浓度和作用时间下对细胞增殖的抑制作用;免疫细胞化学染色检测细胞增殖核抗原(PCNA)的表达;DNA原位末端标记(TUNEL)法和流式细胞术(FCM)检测细胞凋亡。结果:美洛昔康可抑制人肝癌细胞HepG2增殖;TUNEL及FCM检测结果均显示美洛昔康可诱导HepG2细胞凋亡。结论:美洛昔康可通过抑制细胞增殖和诱导凋亡2种途径抑制人肝癌细胞HepG2的生长。     

美洛昔康片剂溶出度的考察

对美洛昔康片剂的溶出条件和方法进行了考察,并用分光光度法测定了美洛昔康片剂的溶出度,结果表明本法简便,准确性高,美洛昔康片剂溶出性能良好。     

四厂家美洛昔康片溶出度考察

目的考察不同厂家生产的美洛昔康片的体外溶出度,为药品采购及临床用药提供参考。方法采用转篮法进行体外溶出度实验,以HPLC-UV进行含量测定,计算累积溶出百分率。以威布尔方程拟合溶出参数T50、Td、T80、m,再对参数进行方差分析。结果 4个厂家美洛昔康片的溶出度体外均符合2005版《中国药典》规定,而美洛昔康片B与美洛昔康片A与其他产家的美洛昔康片的T50、Td、T80、m间差有统计学意义(P<0.01)。结论不同厂家的美洛昔康片的内在质量存在差异。     

应用微渗析技术在大鼠中考察2种促渗剂对美洛昔康的渗透促进作用

目的考察薄荷油(MO)和azone 2种促渗剂对美洛昔康的渗透促进作用。方法用大鼠为实验动物,采用微渗析技术进行在体取样,以HPLC法测定样品中的药物浓度;应用反向渗析法测定探针的在体回收率,以计算药物在皮肤中的浓度。结果在实验条件下微渗析探针的体外回收率主要受灌注液流速的影响,为(50.16±2.34)%;反向渗析法测得探针的在体回收率为(14.096±0.58)%;MO的体积分数为3%和5%时,增渗倍数分别为3.8、17.6;azone的体积分数为3%和5%,增渗倍数分别为9.2、24.8。结论不同体积分数的MO和azone均可显著增加美洛昔康经皮渗透稳态流量,azone的体积分数为5%时,大鼠角质层的屏障作用可能受到了较大程度的破坏。     

血液微渗析技术研究酮洛芬在大鼠体内的药代动力学

目的考察酮洛芬微渗析体内外回收率及影响因素，研究酮洛芬静脉给药后非结合型药物在大鼠体内的药代动力学。方法大鼠颈静脉插入探针后，依次用不同浓度的灌注液对探针进行灌注，测定酮洛芬体内回收率及非结合型酮洛芬在大鼠体内的药代动力学。以高效液相色谱法测定微渗析液中药物浓度。体外回收率的测定采用浓差法。结果增量法及减量法测定的回收率一致。以浓差法测定的体外回收率为28.75%；反渗析法测定体内回收率为(40.3±2.7)%。酮洛芬静脉给药后非结合型药物的T_1/2，AUC和CL分别为(181±16) min，(112±27) μg·min·mL^-1和(0.22±0.05) min^-1。结论血液微渗析技术可用于研究非结合型酮洛芬在大鼠体内的药代动力学。     

用高效液相色谱方法测定人血浆中美洛昔康浓度

建立了测定人血浆中美洛昔康浓度的HPLC UV检测法 .以吡罗昔康为内标物 ,血浆样品经液 液萃取处理后进行HPLC检测 .线性范围为 2 0 0～ 2 0 0 0 0ng/mL ,最低定量限为 2 0 0ng/mL     

Effect of fatty acids on the transdermal delivery of donepezil: in vitro and in vivo evaluation

The effect of fatty acids on the skin permeation of donepezil base (DPB) and its hydrochloride salt (DPH) were studied in vitro using hairless mouse and human cadaver skin. DPB and DPH were solubilized in propylene glycol (PG) containing 1% (w/v) fatty acid, after which the in vitro permeation through hairless mouse skin and human cadaver skin were evaluated using Keshary-Chien diffusion cells. The optimized formulation obtained from the in vitro study was then tested in rats for an in vivo pharmacokinetic study. The relative in vitro skin permeation rate of donepezil (DP) through the hairless mouse skin showed a parabolic relationship with increased carbon length of the fatty acid enhancers. Among the fatty acids tested, oleic acid for DPB and palmitoleic acid for DPH showed the highest enhancing effect, respectively. Both the permeation rates of DPB and DPH evaluated in human cadaver skin were in good correlation with those in hairless mouse skin, regardless of the presence of fatty acids. This suggests that the mouse skin model serves as a useful in vitro system that satisfactorily represents the characteristics of the human skin. Moreover, based on the in vitro results, the optimal formulation that could maintain the human plasma concentration of 50 ng/mL was determined to be 10mg DP with 1% (w/v) enhancer. When the DP transdermal formulations were applied to the abdominal skin of rats (2.14 cm(2)), the C(ss) was maintained for 48 h, among which the highest value of 52.21 ± 2.09 ng/mL was achieved with the DPB formulation using oleic acid. These results showed that fatty acids could enhance the transdermal delivery of DP and suggested the feasibility of developing a novel transdermal delivery system for clinical use.     

Transdermal drug delivery systems of albuterol: in vitro and in vivo studies.

In vitro and in vivo experiments were conducted with double- and single-layer albuterol transdermal pads designed for once-a-day application. In the in vitro experiments, dissolution of albuterol from pads and permeation of albuterol through hairless mouse skin were monitored. In the in vivo experiments, pads were applied to the chest area of four female rhesus monkeys (Macaca mulata), and an albuterol aqueous solution was injected into the saphenous vein of the same animals in a crossover design. The amount lost from pads applied to monkeys was monitored by analysis of pad residue. Blood samples were withdrawn at regular intervals and analyzed by a high-performance liquid chromatography-fluorescence method. Skin irritation due to the pad was measured by a modified Draize score test. The amounts released from the two formulations were similar. The amount released was, however, dependent on the technique used and decreased in the following manner: pad dissolution greater than in vivo amount lost from pads applied to monkeys greater than in vitro permeation through hairless mouse skin. The pharmacokinetic parameters determined after intravenous and transdermal administration were as follows: terminal half-life, 2.26 +/- 0.45 h; apparent volume of distribution, 1935 +/- 37.2 mL.kg-1; and total body clearance, 612.0 +/- 118 mL.h-1.kg-1. The average concentrations in serum after application of single- and double-layer pads were 44.60 +/- 16.40 and 62.50 +/- 8.00 ng/mL, respectively. Further, the amount lost from pads applied to monkeys correlated with the respective amount absorbed in monkeys, as calculated from the average concentration in serum and clearance.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of meloxicam/ethanolamine salt formation on percutaneous absorption of meloxicam

This study was undertaken to prepare meloxicam-ethanolamine salts (MX-EAs) that enhance the transdermal delivery of meloxicam. The physicochemical properties of MX-EAs were investigated by solubility measurements, Differential Scanning Calorimetry (DSC), and Infrared Spectroscopy (FT-IR). The DSC thermogram and FTIR spectra indicated that meloxicam formed salts with ethanolamines. The effects of various vehicles on the percutaneous absorption of meloxicam and of its salts across hairless mouse skin were evaluated using a flow-through diffusion cell system at 37°C. Salt formation lowered the melting point of meloxicam and slightly reduced its octanol/water partition coefficient. Meloxicam-monoethanolamine salt (MX-MEA) and meloxicam-diethanolamine salt (MX-DEA) had greater solubilities and trans-dermal permeation rates across hairless mouse skin than meloxicam alone in various vehicles. Moreover, although the solubility of meloxicam-triethanolamine salt (MX-TEA) was generally lower than that of meloxicam, its permeation rate across the skin was higher. The fluxes of meloxicam and its salts were generally lower than those of piroxicam.     

氮酮对喃氟啶透皮吸收的影响

本文研究了喃氟啶软膏剂对小白鼠和裸鼠离体皮肤的透皮吸收。比较了小白鼠和裸鼠皮肤渗透性、药物浓度和透皮吸收促进剂对喃氟啶透皮吸收的影响。实验结果表明，小白鼠皮肤对喃氟啶渗透性大于裸鼠皮肤，采用透皮吸收促进剂和提高药物浓度可大大提高药物的透皮吸收速率。本研究为临床用药和配制喃氟啶软膏剂选择适宜药物浓度和促进剂浓度提供了依据。     

Pharmacokinetics of Huperzine A after transdermal and oral administration in beagle dogs

Comparison of single and multiple dose pharmacokinetics between patches and conventional tablets of Huperzine A (Hup-A) was performed in beagle dogs to evaluate the patches' controlled drug release characteristics in vivo, a newly developed transdermal system for treatment of Alzheimer disease. Results showed that transdermal administration of Hup-A prolonged T(max) value (24h vs. 3h, P<0.01), lowered C(max) value (3.4+/-0.2 ng mL(-1) vs. 9.8+/-1.0 ng mL(-1), P<0.01), and produced a relatively constant serum concentration within 84 h after a single transdermal dose of 4 mg/20 cm(2) Hup-A patches. Following application of the patches, Hup-A serum concentrations increased for approximately 12-24h, reaching an average C(max) of 3.4+/-0.2 ng mL(-1). Thereafter, a serum concentration of at least 2.1 ng mL(-1) was maintained for up to 84 h. The serum concentration was maintained within the range of 2.4-4.3 ng mL(-1) during 2-week wearing period after multiple dosing, and the degree of fluctuation at the steady state of td and po administration was significantly different (0.51 vs. 1.99, P<0.01). This study indicates that Hup-A patches exhibited good controlled-release properties in vivo, maintained a relatively constant serum concentration within 3.5 d after wearing, and are suitable for twice-weekly application.     

Formulation optimization of meloxicam sodium gel using response surface methodology

The influences of a combination of different mechanisms of penetration enhancers on the penetration absorption properties of meloxicam sodium formulations through rat skin were investigated using response surface methodology. A uniform design was applied to prepare model formulations systematically that were composed of four independent variables: the content of ethanol (x(1)), propylene glycol (x(2)), menthol (x(3)), and azone (x(4)). The penetration rate (flux) of meloxicam sodium gel through rat skin was chosen as the response which had to be higher than 400microg/hcm(2) the required flux of meloxicam gel to maintain a therapeutic concentration. The result showed optimal formulation could be obtained from this response surface methodology. Menthol had the greatest potential influence on the penetration absorption of meloxicam sodium, followed by azone, ethanol and PG, respectively. By in vivo study, meloxicam could be determined 1h after topical administration and reached steady-state concentration at about 12h. The bioavailability (%) of the optimal meloxicam sodium gel was about 50.1%.     

微渗析结合RP-HPLC研究盐酸平阳霉素在家兔血中的药代动力学

采用微渗析技术研究盐酸平阳霉素在体药代动力学，用Supelco RP-amide C₁₆柱进行样品的HPLC分析，盐酸平阳霉素的血药浓度用3P87程序处理。结果表明，家兔静注盐酸平阳霉素后，渗析液中的药物浓度在1.04～66.56 μg·mL^-1时，浓度与峰面积有良好的线性关系(R²=0.999 4)。微渗析探针的在体回收率为(42.8±3.4)%(n =6)。所测血药浓度经3P87程序拟合后，药-时曲线符合二室模型，T_1/2α及T_1/2β分别为14.9及60.3 min。因此，该方法可用于盐酸平阳霉素药代动力学研究。