胡椒碱对中枢神经系统功能的影响

 目的研究胡椒碱对动物睡眠的影响及其抗惊厥作用。方法小鼠开野实验；戊巴比妥钠诱导的小鼠睡眠实验；家兔睡眠时相分析；最大电休克发作实验；戊四唑发作阈值实验；鼠脑单胺类递质的测定。结果胡椒碱可明显减少小鼠的自主活动，并明显的延长戊巴比妥钠诱导的小鼠睡眠时间，还能显著增加家兔的深睡眠。胡椒碱有很强的抗小鼠MES和对抗戊四唑引起的小鼠阵挛性发作的作用，并可明显增加小鼠脑内单胺类神经递质5-HT的含量。结论胡椒碱延长家兔的深睡眠和抗惊厥作用可能与其增加脑内5-羟色胺含量有关。     

Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy

Piperine, the active principle of Piper longum, Piper nigrum and Zingiber officinalis, has been reported to enhance the oral bioavailability of phenytoin in human volunteers. The objective of this study was to explore the effect of a single dose of piperine in patients with uncontrolled epilepsy on the steady-state pharmacokinetics of phenytoin. Two groups of 10 patients each receiving either a 150 mg or 200 mg twice daily dose of phenytoin were selected. Twelve hours after the night dose, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h after administration of phenytoin. On the next study day, piperine 20 mg was administered along with phenytoin and samples were collected similarly. The mean plasma drug concentrations at different time points and the pharmacokinetic parameters before and after piperine administration were compared by Student's t-test. Piperine increased significantly the mean plasma concentration of phenytoin at most of the time points in both dose groups. There was a significant increase in AUC((0-12h)) (p < 0.01), C(max) (p < 0.001) and K(a) (p < 0.05) whereas the changes in K(el) and t(max) were not significant. The results showed that piperine enhanced the bioavailability of phenytoin significantly, possibly by increasing the absorption.     

Pharmacokinetic interaction of single dose of piperine with steady‐state carbamazepine in epilepsy patients

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability‐enhancer. The present study aimed at evaluating the effect of piperine on the steady‐state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t‐test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC_0‐12hr (p < 0.001), average C_ss (p < 0.001), t_1\2el (p < 0.05) and a decrease in K_el (p < 0.05), in both the dose groups, whereas changes in K_a and t_1\2a were not significant. Cmax (p < 0.01) and t_max (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption. Copyright © 2009 John Wiley & Sons, Ltd.     

HPLC测定血浆中尼美舒利浓度

 目的：建立测定血浆中尼美舒利(Nim)的反相高效液相色谱法。方法：血浆样品用甲醇沉淀蛋白，经酸化后加甲苯提取，氮气挥干，加流动相溶解进样。以YWG-C₁₈柱，甲醇-0.05mol·L^-1磷酸二氢钾(55∶45)为流动相,pH5.02，甲苯磺丁脲为内标，在波长230nm处检测。结果：在0.26μg·ml^-1～10.8μg·ml^-1浓度范围内，峰面积比与浓度呈良好线性关系，r=0.9995。最低检测限为0.2μg·ml^-1，方法重现性好，方法回收率为86.0%～92.2%，萃取回收率为72.2%～88.4%。结论：用本方法测定8例单剂量po100mg Nim的血药浓度，结果满意。     

儿泻康贴膜中胡椒碱的透皮吸收研究

目的:通过研究儿泻康贴膜中的有效成分——胡椒碱的离体透皮吸收的行为及其定量分析,探讨儿泻康贴膜中的胡椒碱体外透皮的可行性,为中药内病外治提供理论依据。方法:采用Franz扩散池法,用高效液相色谱法测定胡椒碱不同时间对小鼠离体皮肤透皮吸收率。结果:胡椒碱经离体小鼠皮肤的透皮率随时间的增加而增加,52 h后胡椒碱的渗透率为78.51%,且保持基本不变。结论:胡椒碱能透皮吸收,且本方法简单,稳定易行,可控性强,重复性好,可用于儿泻康贴膜中胡椒碱的透皮吸收的测定。     

姜黄素-胡椒碱固体分散体的制备与生物利用度研究

目的将姜黄素(CUR)和胡椒碱(PIP)组合物制成固体分散体(SD),提高CUR、PIP口服吸收率。方法采用溶剂挥发法,以溶出度为指标,利用X射线衍射(XRD)和差示扫描量热分析(DSC)对姜黄素-胡椒碱固体分散体(CUR-PIP SD)进行表征,并运用体外超饱和溶出法对制得的SD进行体外评价。同时应用UPLC-MS/MS研究大鼠ig给药后CUR和PIP的药动学行为。结果体外溶出实验显示,与原料药相比,SD中CUR和PIP溶出度均得到较大提高。大鼠药动学实验结果显示,与原料药相比,SD中CUR的生物利用度提高至2.71倍(P0.05),PIP提高至2.68倍(P0.05)。结论以PVP K30为载体制备的SD能够有效地改善CUR和PIP的体外溶出度以及生物利用度。     

胡椒碱的抗抑郁及神经保护作用研究

目的:观察胡椒碱的抗抑郁及细胞保护作用.方法:利用小鼠强制游泳实验、悬尾实验考察胡椒碱抗抑郁作用;采用皮质酮损伤SH-SY5Y神经细胞和分离培养新生大鼠海马神经前体细胞两种体外模型,测定细胞存活率(MTT法),观察胡椒碱对神经细胞增殖的影响,并初步探讨其抗抑郁的作用机制.结果:胡椒碱(10,20 mg·kg~(-1))给药后,能明显缩短小鼠在行为学实验中的不动状态时间,并且该作用随剂量增大效应逐渐降低;胡椒碱(1.4,7,35μmol·L~(-1))可对抗皮质酮对SH-SY5Y的损伤作用,且对所培养具有神经前体细胞特性的细胞,具有促进神经前体细胞增殖的作用.结论:胡椒碱具有较好的抗抑郁作用,其作用可能是通过调控神经干细胞的增殖、迁移和分化及对功能性神经再生的保护和促进作用实现的.     

RP-HPLC测定六味木香散中胡椒碱含量

 目的:建立六味木香散中胡椒碱含重测定方法。方法:反相液相色谱法。采用Shim-Pack CLC-ODS(15 cm X6 mm)分析柱;ODS保护柱;流动相:甲醇-水(67:33);流速:1.0 ml · min^-1;色语柱温度35℃;检测波长:343 nm;进样体积10μl;外标法计算含量。结果:理论板数按胡椒碱峰计算为3 600;分离度为2.5;胡椒碱浓度在3～48μg·ml^-1范围与色谱峰面积呈线性关系，r = 0.999 9;回收率及RSD分别是98.6%和2.1%。结论:方法简便准确，可用于六味木香散中胡椒碱含量测定。     

荜茇中胡椒碱在大鼠体内的药动学研究

目的:建立大鼠灌胃荜茇提取溶液后血浆中胡椒碱的HPLC测定方法,进行大鼠药动学研究。方法:大鼠灌胃给药(荜茇提取溶液)后,通过尾静脉取血获得血浆样品,以胡椒碱为指标,采取甲醇-水(77:23,v:v)为流动相,HypersilC18柱(250mm×4.6mm,10μm)为固定相,紫外检测波长为343nm进行测定。采用药代动力学软件DAS(ver2.0)处理,得到胡椒碱的药代动力学参数。结果:胡椒碱1.75～8.72g/ml范围内呈良好的线性关系,胡椒碱的三种浓度的平均回收率及相对标准偏差分别为88.4%(3.5%)、90.4%(2.8%)、85.9%(5.2%)。胡椒碱在大鼠体内的药代动力学过程符合一室吸收模型,主要药动学参数为tmax1/2=60min,高低剂量分别t1/2=138.78min和t1/2=125.87min,Cmax=0.46和0.27mg/L,AUC(0-t)=42.45和66.47mg/L.min,AUMC(0-t)=5355.17和7811.02。结论:荜茇在大鼠血浆中胡椒碱浓度的测定和临床前药代动力学研究。     

蒙药荜茇三味胶囊提取工艺的研究

目的:优选蒙药荜茇三味胶囊的提取条件。方法:采取正交实验法,用高效液相色谱法,以测定提取物中胡椒碱的含量为指标,考察乙醇浓度(A)、乙醇用量(B)、提取时间(C)、提取次数(D)等4个条件对提取效果的影响;进行四因素三水平试验。结果:实验设计因素中乙醇用量的影响最为显著。结论:荜茇三味胶囊的最佳提取工艺条件为A_1B_1C_1D_2,即每次加入药材6倍量的65%乙醇,提取2次,每次提取60min。     

HPLC法测定蒙药当玛-5中胡椒碱的含量

目的：建立蒙药当玛-5中胡椒碱的高效液相含量测定方法。方法：采用高效液相色谱法,用C18色谱柱（150×4.6mm）,以甲醇-水（77：23）为流动相,流速为0.6m l/m in,检测波长为343nm,定量法为外标法。结果：胡椒碱的线性范围为0.0345μg~0.0805μg（r=0.9998）,平均加样回收率为99.50%,RSD=1.09%。结论：该方法灵敏、准确、重复性好,可用于蒙药当玛-5的质量控制指标。     

用药效学试验筛选尼美舒利新剂型

 目的通过比较尼美舒利栓剂、搽剂、口服水混悬液的药效学试验结果，为尼美舒利新制剂的开发和剂型选择提供依据。方法采用二甲苯引起小鼠耳壳肿胀炎症模型，观察尼美舒利新制剂的抗炎作用；采用醋酸扭体法，观察尼美舒利新制剂的镇痛作用；采用伤寒Vi多糖疫苗引起家兔发热模型，观察尼美舒利新制剂的解热作用；比较尼美舒利直肠栓剂和尼美舒利口服片剂的生物利用度；进行生物等效性分析。结果尼美舒利栓剂、搽剂、口服水混悬液均可明显减轻小鼠耳壳肿胀度、减少扭体次数、有明显的解热作用。尼美舒利栓剂的相对生物利用度为84.75%；尼美舒利栓剂与尼美舒利片剂生物不等效。结论尼美舒利栓剂具有良好的解热、镇痛、抗炎作用；尼美舒利栓剂的吸收速度快于片剂。     

The effect of topical piperine combined with narrowband UVB on vitiligo treatment: A clinical trial study

Vitiligo is the most common acquired hypopigmentary disease in the community. Piperine as an herbal extract derived from black pepper has strong impact on the melanocyte proliferation and adverse side effects less than synthetic drugs such as corticosteroids. For the first time, this study was aimed to evaluate the effect of topical piperine combined with narrowband ultraviolet B (NB‐UVB) on vitiligo treatment. In this double‐blind clinical trial, 63 patients with facial vitiligo were randomly divided into 2 groups: treated with piperine (case) and placebo (control). Also, both groups received NB‐UVB phototherapy every other day for 3 months. In the case group, 10 patients have burning sensation on their skin areas (p value = .002). Also, redness of the treated areas was observed in 6 patients (p value = .028). Both side effects were temporary. Regarding repigmentation at time intervals of 1, 2, and 3 months after treatment, its level in the case group was significantly higher than the control group (p value < .001). Based on our findings, the combination therapy with NB‐UVB/topical piperine has more influence on facial vitiligo than that of NB‐UVB alone. It could be concluded that the simultaneous use of NB‐UVB and topical piperine has a remarkable effect on treatment of vitiligo.     

荜茇有效部位群的调血脂研究

研究荜茇有效部位群对高脂血症的影响.将SD大鼠、金黄地鼠及昆明小鼠均分为空白组、模型组、阳性组和受试组,空白组饲喂普通饲料,其他组饲喂高脂饲料(小鼠实验腹腔注射蛋黄乳),每天依次灌胃给予相应浓度的赋形剂、赋形剂、辛伐他汀、荜茇有效部位群乳剂,一定时期后测定动物血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)及肝脏TC,TG的含量,以反映荜茇有效部位群的调血脂功能.结束后,与空白组比较,成功造成SD大鼠(TC升高)、小鼠(TC,TG,LDL升高),地鼠(TC,TG,LDL升高,HDL降低)高脂血症模型(P＜0.05,P＜0.001);与模型组比较,荜茇有效部位群既能降低血清TC,TG,LDL(P＜0.05,P＜0.001)和肝脏TC,TG含量,又能升高血清HDL含量(P ＜0.05,P＜0.001).从而证明荜茇有效部位群具有显著调节血脂功能,金黄地鼠为造高脂血症模型较理想的动物.     

丹皮酚、丁香酚、胡椒碱经皮微透析体内外回收率的研究

建立活血止痛膏中有效成分丹皮酚、丁香酚、胡椒碱微透析体内外回收率校正方法,为其经皮药动学研究提供依据。利用高效液相色谱法测定透析液中丹皮酚、丁香酚、胡椒碱的浓度,并计算微透析探针回收率;研究浓度、校正方法对3种成分微透析探针回收率的影响,并考察探针吸附性、体内外回收率的稳定性和重复性。结果表明,以30%乙醇生理盐水作为灌流液时,探针对3种成分均无明显的吸附,短时间内即可从探针上被完全洗脱下来;在8 h内,3种成分体内外回收率均能保持稳定;交替用含药溶液和空白灌流液灌流探针3次,3种成分体内外回收率基本不变。不同质量浓度丹皮酚(2.46~53.64 mg·L~(-1))、丁香酚(4.26~32.15 mg·L~(-1))和胡椒碱(5.75~45.87 mg·L~(-1))体外回收率分别为(45.7±4.66)%,(41.3±3.96)%,(27.82±2.95)%,即3种成分的探针回收率对浓度没有依赖性;在相同条件下,零净通量法、透析法和反透析法所测得的探针体外回收率几乎相等。因此,采集部位药物的浓度可用体外测得的回收率或在体回收率进行校正。同时也证明了该研究建立的微透析方法可用于活血止痛膏的经皮药动学研究。     

尼美舒利随机对照治疗类风湿关节炎171例

 目的：比较研究尼美舒利(Nim)和萘普生(Nap)治疗类风湿关节炎的疗效和安全性。方法：试验设计为随机、对照、平行性和多中心的比较研究。试验组病例数为171例，其中双盲试验60例，单盲试验111例，每次poNim100mg·，bid，疗程2周，累积用药4周者78例，12周者50例；对照组病例数为112例，其中双盲试验61例，单盲试验51例，每次poNap250mg·，bid，疗程2周，累积用药4周者62例，12周者51例。结果：2，4，8周时Nim的总有效率分别为63.61%，67.95%和98.00%，Nap的总有效率分别为53.87%，59.68%和76.47%。两药均能显著改善患者的症状和体征，降低血沉、C反应蛋白水平。经安全性评价：Nim和Nap的耐受性相似，2，4，12周时Nim的不良反应发生率分别为27.49％，3.77%，28.00%；Nap的不良反应发生率分别为32.14%，35.48%，43.13%。结论：Nim治疗类风湿关节炎的疗效在2，4周时与Nap相近，在12周时好于Nap；Nim的不良反应发生率稍低于Nim，但无显著性差别。     

A systematic review and meta-analysis of randomized controlled trials investigating the effect of the curcumin and piperine combination on lipid profile in patients with metabolic syndrome and related disorders

Metabolic syndrome is characterized by multiple metabolic disorders. Several studies indicated that curcumin plus piperine could affect lipids profiles in various diseases. The present meta-analysis aims to assess the effect of curcumin plus piperine on lipid profiles in patients with MetS and associated disorders using a systematic review and meta-analysis of randomized controlled trials. Trials were searched by several electronic databases up to May 2022. The Comprehensive Meta-Analysis (CMA) version3 software carried out this systematic review and meta-analysis. Random-effects model and the inverse variance method were used to conduct the meta-analysis. We evaluated the publication bias and heterogeneity of all eligible studies. In addition, subgroup analyses and sensitivity assessments were performed to assess potential sources of heterogeneity. The combined results by the random-effects model demonstrated that curcumin plus piperine significantly decreased total cholesterol and LDL-C in patients suffering from metabolic syndrome. In comparison, the results of the overall effect size did not show any significant change in triglyceride concentrations. Our results were robust in sensitivity analysis and were not dependent on the dose of curcumin, the dose of piperine, and the duration of treatment. Our results showed that co-administration of piperine and curcumin supplementation improves the lipid profile in metabolic syndrome. However, further long-term RCTs are required to ascertain their clinical benefit.     

苯唑青霉素对丁胺卡那毒素药动学的影响

 采用微量微生物法对丁胺卡那霉素（AMK）单用及AMK与苯唑青霉素（OXA）合用后，兔体内AMK血药浓度进行测定；药时数据用MCPKP软件经IBM计算机处理，并对两组药动学参数进行了统计学处理，结果表明OXA对AMK的药动学有显著的影响。     

Piperine Inhibits Lipopolysaccharide‐induced Maturation of Bone‐marrow‐derived Dendritic Cells Through Inhibition of ERK and JNK Activation

Piperine, one of the main components of Piper longum Linn. and P. nigrum Linn., is a plant alkaloid with a long history of medicinal use. Piperine has been shown to modulate the immune response, but the mechanism underlying this modulation remains unknown. Here, we examined the effects of piperine on lipopolysaccharide (LPS)‐induced inflammatory responses in bone‐marrow‐derived dendritic cells (BMDCs). Piperine significantly inhibited the expression of major histocompatibility complex class II, CD40 and CD86 in BMDCs in a dose‐dependent manner. Furthermore, piperine treatment led to an increase in fluorescein‐isothiocyanate–dextran uptake in LPS‐treated dendritic cells and inhibited the production of tumour necrosis factor alpha and interleukin (IL)‐12, but not IL‐6. The inhibitory effects of piperine were mediated via suppression of extracellular signal‐regulated kinases and c‐Jun N‐terminal kinases activation, but not p38 or nuclear factor‐κB activation. These findings provide insight into the immunopharmacological role of piperine. Copyright © 2012 John Wiley & Sons, Ltd.     

联合用药对阿霉素兔体内药动学的影响

目的：讨论单独使用阿霉素及阿霉素与其他药物配伍应用时的药动学参数变化。方法：采用荧光分光光度法，测定家兔体内阿霉素血药浓度。结果：阿霉素分别与顺铂、丝裂霉素、 甲氨喋呤配伍，阿霉素与顺铂、丝裂霉素，阿霉素与顺铂、甲氨蝶呤联合应用时，在家兔体内的消除速度较单一用药快。顺铂能明显减小阿霉素从中央室向周边室的转运速度，丝裂霉素可提高阿霉素的生物利用度。结论：阿霉素与顺铂（或丝裂霉素）联用时, 应适当减少阿霉素的使用剂量，以避免阿霉素可能产生的不良反应。