酮洛芬缓释片人体药动学和生物等效性研究

目的:评价受试酮洛芬缓释片与参比酮洛芬片的生物等效性。方法:采用反相高效液相色谱法测定24名健康男性志愿受试者交叉单剂量口服受试酮洛芬缓释片与参比酮洛芬片150mg后血浆中酮洛芬的浓度,用3p97程序进行数据处理。结果:口服受试和参比酮洛芬制荆后的AUC_(0-(?))分别是38.94±9.15μg·h·ml~(-1)、38.04±6.90μg·h·ml~(-1);AUC_(0-(?))分别是44.50±8.09μg·h·ml~(-1)、42.99±8.36μg·h·ml~(-1);T_(max)分别是3.87±0.55 h、1.96±0.60h;C_(max)分别是5.78±1.11μg·ml~(-1)、11.62±2.10μg·ml~(-1);t_(1/2)(Ke)分别是5.88±1.16h、1.70±1.40h。结论:受试酮洛芬缓释片与参比酮洛芬片具有生物等效性。     

盐酸氯苯胍在美国红鱼体内的药代动力学和残留消除规律研究

在水温(28±2)℃、盐度28条件下,盐酸氯苯胍(robenidine hydrochloride,ROBH)按30 mg/kg的剂量口灌实验鱼,用HPLC-MS/MS法研究盐酸氯苯胍在美国红鱼体内的药代动力学和残留消除规律。结果显示,单剂量口灌给药后,美国红鱼血浆中ROBH的药时数据符合一级吸收二室模型,药物在血浆中的达峰时间(tp)、血药浓度峰值(Cmax)、药时曲线下面积(AUC_(0-∞))和消除半衰期(t_(1/2β))分别为2.39 h、958.78μg/L、33 247.57μg/(L·h)和19.24 h;ROBH在肌肉、肝脏和肾脏的Cmax分别为156.72μg/kg、227.68μg/kg和553.44μg/kg,tp分别为2.0 h、1.5 h、2.0 h;AUC_(0-∞)分别4 664.04μg/(kg·h)、4 897.74μg/(kg·h)、17 228.19μg/(kg·h);t_(1/2β)分别为19.68 h、24.33 h和22.81 h。按30 mg/kg剂量连续5 d口灌给药后,美国红鱼肌肉、肝脏、肾脏中的药物消除半衰期(t1/2):24.46 h、35.39 h、39.60 h和33.94 h。若以10μg/kg为最高残留限量,肌肉作为食用靶组织,在本试验条件下,建议休药期不少于7 d。     

双斑长跗萤叶甲对棉花和玉米七种挥发物的EAG及行为反应

【目的】为筛选适合配制双斑长跗萤叶甲Monolepta hieroglyphica(Motschulsky)引诱剂的有效成分。【方法】本试验采用昆虫触角电位反应仪和"Y"型嗅觉仪测定了双斑长跗萤叶甲雌、雄成虫对棉花和玉米7种挥发物的电生理反应和行为反应。【结果】双斑长跗萤叶甲雌、雄成虫均对10μg·mL~(-1)和1μg·mL~(-1)的γ-萜品烯、10μg·mL~(-1)的D-柠檬烯、10μg·mL~(-1)的β-紫罗酮的EAG反应较明显,对10μg·mL~(-1)和10~(-2)μg·mL~(-1)的α-石竹烯和10μg·mL~(-1)、1μg·mL~(-1)和10-2μg·mL~(-1)的氧化石竹烯的反应次之,对十二烷、十三烷的反应较不明显。t-检验表明,雌、雄成虫对挥发性物部分浓度的EAG反应存在显著差异。行为反应测定结果表明,在10μg·mL~(-1)刺激剂量条件下,β-紫罗酮对雌虫表现出明显的引诱作用,γ-萜品烯和氧化石竹烯对其有显著的驱避作用;γ-萜品烯和D-柠檬烯对雄虫具有显著的引诱作用,β-紫罗酮对其具有显著的驱避作用。【结论】该研究结果可为双斑长跗萤叶甲田间引诱剂的研发提供借鉴。     

绒盖牛肝菌酸HPLC检测方法的建立及在大鼠体内的药代动力学

为建立绒盖牛肝菌酸血药浓度和各主要组织的HPLC检测方法,考察绒盖牛肝菌酸在大鼠体内的药代动力学和组织分布特点。采用Agilent ZORBAX Eclipse XDB-C18 column色谱柱(4.6 mm×250 mm,0.5μm)分离,以V(甲醇)∶V(水)=75∶25为流动相,流速1.0 m L/min,柱温25℃,检测波长243 nm。研究结果表明大鼠血浆及肝组织中的内源性物质均不干扰样品的测定,线性关系良好,大鼠灌胃绒盖牛肝菌酸符合一室模型,主要药代动力学参数Tmax为(0.76±0.21)h,Cmax为(8.76±0.81)μg/m L,t1/2为(0.18±0.28)h,AUC0-inf为(102.95±0.78)μg/(m L·h),大鼠尾静脉注射绒盖牛肝菌酸符合二室模型,主要药代动力学参数t1/2为(0.33±0.71)h,AUC_(0-inf)为(34.14±2.38)μg/(m L·h)。该方法简单快速,准确可靠,符合生物样品的测定要求,并明确了绒盖牛肝菌酸在大鼠体内的药代动力学和组织分布特征。     

当归中藁本内酯在大鼠体内的药代动力学研究

采用超高效液相色谱(UPLC-PDA)法测定大鼠灌胃当归石油醚萃取物后藁本内酯的血药浓度。色谱条件:色谱柱BEH C18(2.1 mm×100 mm,1.7μm);流动相:乙腈-水(0.03%三氟乙酸)(45∶55,v/v);流速:0.5mL/min;检测波长:320 nm。并运用DAS 3.0药动学软件计算药动学参数,研究当归石油醚萃取物中藁本内酯在大鼠体内的药代动力学。结果显示藁本内酯在大鼠体内较符合二室模型,主要的药动参数:高、中剂量组的Cmax分别为0.38±0.04、0.33±0.02(μg/mL);t1/2β分别为4.08±0.25、3.06±0.82(h),低剂量组含量过低,无法进行定量。实验结果表明UPLC-PDA法能够较准确、灵敏的测定藁本内酯在大鼠体内的血药浓度,经比较高、中剂量组的药动参数得知,该物质呈非剂量依赖型。     

RP-HPLC法测定阿托伐他汀在新西兰兔体内的药代动力学

目的:研究阿托伐他汀片在新西兰兔体内的药代动力学.方法:18只成年健康雄性新西兰兔.随机分为正常对照组、10mg/kg·d阿托伐他汀片组与15 mg/kg·d阿托伐他汀片组,每组6只,采用RP-HPLC法测定血药浓度,计算药代动力学参数.结果:10mg/kg·d组与15 mg/kg·d组的主要药代动力学参数分别为:AUC0～t/μ g·L-1·h为(619.58±215.45)与(1138.34±422.32)、AUC0～∞/μ g·L-1·h为(655.68±242.83)与(1216.57±353.64)、Cmax/μ g·L-1为(455.81±168.52)和(896.53±168.5.8)、MRT0～t/h为(3.68±0.75)与(5.73±0.56)、MRT0～∞/h为(3.83±0.91)与(5.25±0.48)、Tmax/h为(2.51±0.82)与(3.68±0.33)、T1/2/h为(4.22±0.55)与(9.51±0.67).结论:RP-HPLC法适用于阿托伐他汀片动物药代动力学的研究.     

绒毛崖豆藤中一种查尔酮提取物的体内外代谢及药代动力学研究CSCD

采用UPLC-QE-Orbitrap-MS检测方法,通过比较2,5-二甲氧基呋喃[4″,5″:3,4]查耳酮(1)在体外大鼠、小鼠、恒河猴、Beagle犬和人五个种属肝微粒体体系中孵育0 min和60 min的样品,以及比较静脉注射该化合物及空白的C57小鼠的血浆、粪便、尿液样品,研究其在体内外代谢产物。初步推断孵育后体外代谢产物有M1、M2共2种,体内代谢产物M1、M2、M3、M4、M5共5种,并且M5为M1进一步代谢而来,采用化学合成方法制得代谢产物M1。将大鼠随机分组并给药,于设定的系列时间点取血,采用超高速液相色谱质谱联用(UFLC-MS/MS)检测方法,测定1及M1血药浓度,定量研究该化合物及M1在大鼠体内的变化趋势并计算药代参数。用DAS 2.0软件计算药代动力学参数,1的C_(max)=405.96μg/L,Tmax=0.083 h,AUC_(0-t)=190.64μg/(L·h),T_(1/2)=3.74 h,M1的C_(max)=281.291μg/L,T_(max)=0.083 h,AUC_(0-t)=561.30μg/(L·h),T_(1/2)=3.01 h。研究结果表明,2,5-二甲氧基呋喃[4″,5″:3,4]查耳酮在体内代谢过程中主要发生了还原、去甲基、开环、加羟基等反应,其中主要代谢产物为M1,并且M1进一步代谢为M5,本研究为揭示其药理药效作用奠定了物质基础。     

孟鲁斯特钠咀嚼片在健康人体内药动学和生物等效性

目的:研究两种(仿制新药与市售)孟鲁司特钠咀嚼片在人体内生物等效性。方法:采用单中心、随机、开放、双周期自身交叉试验设计,20名健康男性志愿者分2周期分别口服受试制剂和参比制剂各10 mg,HPLC法测定血浆中孟鲁司特钠咀嚼片的浓度,用DAS2.1.1软件计算人体药动学参数并进行生物等效性评价。结果:受试制剂和参比制剂两药的主要药代动力学参数AUC0-t分别为(17.94±6.19)μg h/ml和(17.37±4.73)μg h/ml,AUC0-∞分别为(18.26±6.16)μg h/ml和(17.64±4.66)μg h/ml,Cmax分别为(5.58±1.95)μg/ml和(5.54±1.65)μg/ml,Tmax分别为(2.03±0.97)h和(1.93±0.69)h,t1/2分别为(1.20±0.17)h和(1.19±0.13)h。受试制剂的平均相对生物利用度为(101.5±6.56)%。结论:受试制剂和参比制剂具有生物等效性。     

头孢氨苄胶囊制剂人体生物等效性研究

目的:研究新仿制的头孢羟氨苄胶囊制剂与市场在售的同类制剂在健康人体内的生物等效性。方法:采用随机交叉试验设计,20名健康男性志愿者分别口服受试制剂与参比制剂500 mg,HPLC法测定血浆中头孢氨苄的浓度,用DAS 2.0软件计算药动学参数并进行生物等效性评价。结果:受试制剂和参比制剂两药的主要药代动力学参数,Cmax分别为(18.12±3.17)μg/ml和(21.28±3.77)μg/ml,Tmax分别为(1.09±0.37)h和(1.04±0.33)h,t1/2分别为(1.15±0.22)h和(1.14±0.20)h,AUC0-t分别为(35.43±5.39)μg h/ml和(37.27±4.76)μg h/ml,AUC0-∞分别为(36.68±6.06)μg h/ml和(38.62±5.48)μg h/ml,受试制剂的平均相对生物利用度为(96.50±7.2)%。结论:受试制剂和参比制剂具有良好的生物等效性。     

对羟基苯甲酸及其钠盐在小鼠和食蟹猴体内药代动力学及组织分布研究CSCD

前期研究表明对羟基苯甲酸(p-HBA)及其钠盐对羟基苯甲酸钠(s-HBA)均为治疗溃疡性结肠炎的潜在药物。本文研究p-HBA及s-HBA单次给药在正常小鼠体内药代动力学及组织分布特征,以及单次给药s-HBA后食蟹猴体内药代动力学特征。小鼠灌胃给予20 mg/kg的p-HBA和20、50、100 mg/kg的s-HBA,以及食蟹猴灌胃给予4、10、20 mg/kg的s-HBA。LC-MS/MS测定p-HBA和s-HBA在小鼠血浆和组织中的浓度,以及s-HBA在食蟹猴血浆中的浓度。所有血浆和组织均使用乙腈沉淀蛋白法处理。p-HBA及s-HBA在20 mg/kg的剂量下,血浆达峰时间T_(max)分别为0.08、0.08 h,达峰浓度C_(max)分别为20453.98、30683.33 ng/kg,时间曲线下面积AUC_(0-t)分别为7180.27、12008.42 ng·h/mL,半衰期t_(1/2)分别为0.57、0.59 h。s-HBA在小鼠和食蟹猴体内,C_(max)和AUC_(0-t)与剂量均呈良好的线性关系。分别给药p-HBA及s-HBA后,在小鼠的心,肝,脾,肺,肾,脑和结肠组织中均能检测到较高浓度的p-HBA。结果表明,p-HBA及s-HBA灌胃给药后在小鼠和食蟹猴体内吸收和消除均较快,在小鼠体内组织分布广泛,以肾和肝浓度最高,推测其对肾和肝有一定的靶向性,所有组织均无明显蓄积,提示安全性良好。     

六种藓类植物茎的比较解剖学研究

通过对6种藓类植物,即褶叶青藓(Brachythecium salebrosum(Web.et Mohr.)B.S.G.)、湿地匐灯藓(Plagiomnium acutum(Lindb.)Kop.)、侧枝匐灯藓(Plagiomnium maximoviczii(Lindb.)Kop.)、大凤尾藓(Fissidensnobilis Griff.)、大羽藓(Thuidium cymbifolium(Doz.et Molk.)B.S.G.)和大灰藓(Hypnum plumaeforme Wils.)嫩茎和老茎的石蜡切片和显微观察发现,同一藓类植株的嫩茎和老茎,茎结构稳定,不同种藓类植物茎横切面具有不同特征.植物体茎横切面形状、表层细胞的层数、细胞大小和细胞壁厚薄、皮层细胞大小和形状、中轴的有无以及比例等特征可以作为藓类植物的分科分类依据之一.     

Photoregulation of seed germination of wild-type and of an aurea-mutant of tomato

Seed germination of an aurea mutant of tomato ( Lycopersicon esculentum Mill.) is promoted by continuous irradiation with red, far-red or long-wavelength far-red (758 nm) light as well as by cyclic irradiations (5 min red or 5 min far-red/25 min darkness). Far-red light applied immediately after each red does not change the germination behaviour. Seed germination of the isogenic wild-type, cv. UC-105, is promoted by continuous and cyclic red light while it is inhibited by continuous and cyclic far-red light and by continious 758 nm irradiation. Far-red irradiation reverses almost completely the promoting effect of red light. The promoting effect (in the aurea mutant) and the inhibitory effect (in the wild-type) of continuous far-red light do not show photon fluence rate dependency above 20 nmol m⁻² s⁻¹. It is concluded that phytochrome controls tomato seed germination throgh low energy responses in both the wild type and the au mutant. The promoting effect of continuous and cyclic far-red light in the au mutant can be attributed to a greater sensitivity to P_fr.     

Cause of Senescence of Nine Sorts of Flowers

The levels of endogenous phytohormones and respiratory rate in nine sorts of flowers such as Cymbidium faberi Rolfe, Nopalxochia ackermannii Kunth and others were investigated both at full bloom and senescence and meanwhile the effect of exogenous phytohormones on prolonging the blossoms and promoting ethylene production were tested. There is a high content of endogenous ethylene in all the long-lived flowere, about 3–16 folds higer than the short-lived ones. There is a high level of ABA at full blooming flowers of short-lived flowers, in which there is no or only some cytokinins in it, but the ratio of CTK (6BA+zeatin)/ABA is smaller(l.7). The endogenous ABA reached a much higher level at senescence in all nine sorts of flowers, so it is reasonable to consider that it is ABA which plays an important role of regulation in controlling flower's senescence. There is a much higher level of GA3 and zeatin in the long-lived flowers which is not demonstrated in the shortlived ones. The respiratory rate is one of the factors controtling the longevity of flowers, but it does not play a decided role. Application of 6BA and zeatin prolongs distinctly orchid’s longevity, however exogenous IAA through the promotive action on ethylene production, evidently extends the longevity of the flowers of the Nopalxochia ackermannii Kunth.     

真菌类遗传学分析的知识结构教学

本文以认知结构理论为指导,讨论了真菌类遗传分析与高等动植物遗传分析的内在联系,认为利用这种内在联系进行教学可收到好的效果并说明了作者的具体教学过程。 Abstract:In the paper, the relationship between genetic analysis of Fungi and genetic analysis of high animal and plant was discussed.A good results were obtained when we adopted this method in the teaching.     

龙胆科药用植物化学成分的研究现状

龙胆科植物在我国的分布范围很广,且多数为药用植物,其多数种属的药用植物,至今其化学成分尚未被系统研究。综述了目前龙胆科药用植物的化学成分的研究现状及一般提取方法,对近年来发现的环烯醚萜及裂环烯醚萜类化合物进行了总结,为本科药用植物的更深入研究提供了参考。     

Interconnection of parameters of regulation system of lipid peroxidation and of morphophysiological parameters of mouse liver

A complex analysis of seasonal fluctuations of the mean group parameters of the system of regulation of lipid peroxidation has been performed in liver of Balb/c mice. Association of lipid characteristics and morphophysiological parameters is studied in the Balb/c mouse liver. An inter-connection is revealed between the liver index and the amount of lysoforms of phospholipids, the scale and character of the interconnection differing essentially depending on proportion of phos-phatidylcholine in mouse liver phospholipids.     

The effects of glutamine of the maintenance of embryogenic cultures of Cryptomeria japonica

Summary Embryogenic tissues of sugi (Cryptomeria japonica) were induced on a modified Campbell and Durzan (CD) medium containing 1 μM 2,4-dichlorophenoxyacetic acid (2,4-D) and 600 mg l⁻¹ glutamine, and subcultured in the medium of the same composition for over 1 yr. This resulted in a mixed culture of embryogenic and non-embryogenic cells. When embryogenic cells were isolated and cultured independently, their capacity to form embryogenic aggregates was lost. Thus, the non-embryogenic cells present within a mixed culture system were essential to the formation of embryogenic aggregates. When embryogenic tissues were isolated and cultured independently on a high glutamine-containing (2400 mg l⁻¹) medium, dry weights and endogenous levels of glutamine increased, and the tissue could generate a large number of embryogenic aggregates. Amino acid analysis of embryogenic and non-embryogenic cells from the maintenance culture indicated a higher level of glutamine was present in the latter. The high endogenous level of glutamine in the non-embryogenic portion of mixed cell masses may be the supplier of glutamine for maintaining the embryogenic property of the tissues.     

Specificity of action of piperidylcholine derivatives as substrates of cholinesterases of various origin

The review deals with study of enzymologic properties of a novel highly specific acetylcholinesterase substrate, N-(β-acetoxyethyl) piperidinium iodomethylate (“piperidylcholine”), and its 30 derivatives that were tested as effectors of cholinesterases of mammals and various species of Pacific squids. It was proven for the first time that responsible for specificity of action was structure of cyclic ammonium grouping of the alcohol part of molecule of the ester substrate. Analysis of specificity is performed based on enzymatic hydrolysis parameters—activity of catalytic center of cholinesterases and bimolecular constant of the reaction rate that are determined at optimal and low substrate concentrations. Among the specially synthesized group of thioester compounds there is revealed one more highly specific acetylcholinesterase substrate—N-(β-acetoxyethyl) piperidinium.