疯草解毒复方中药制剂的药代动力学研究

本试验旨在探讨疯草解毒用复方中药制剂在大鼠体内的药代动力学特性。在确定制剂中有效成分的基础上,采用紫外分光光度法检测大鼠经口服药物制剂后体内有效成分的吸收情况,并计算相应的药代动力学参数。本试验建立了适用于检测8种成分的紫外光谱分析法;制剂经口服给药后能在胃肠道被快速吸收,1 h左右大鼠体内各组分的血药浓度达到最大,药效发挥迅速;党参皂甙、多糖和阿魏酸代谢速度快,甘草酸、柴胡皂苷、黄芪甲苷、升麻素苷的代谢产物在体内作用时间较长。复方中药制剂在试验大鼠体内的药代动力学过程基本符合二室模型(陈皮苷除外)。所选用的测定方法简便、准确度和稳定性较高,适用于该制剂的药代动力学研究。     

新型兽用纳米乳载药系统在大鼠体内的药代动力学研究

为了解氟苯尼考纳米乳(FFNE)在大鼠体内药代动力学行为,本试验以氟苯尼考溶液(FFSol)为参比制剂,以30 mg/kg剂量给大鼠灌胃和肌内注射给药,分别于给药后0.5、1、2、4、8、12、24、36、48、72 h采血,利用高效液相色谱法测定血浆中氟苯尼考含量,利用DAS 2.0软件计算房室模型与非房室模型条件下药代动力学参数。结果显示,在两种给药方式下,FFNE与FFSol在大鼠体内均符合二室模型。灌胃给药后,FFNE与FFSol在房室模型条件下AUC_(0-∞)分别为1 085.047和2 176.490 mg/L·h,半衰期分别为10.566和13.687 h,FFNE的相对生物利用度为187.4%。肌内注射给药后,FFNE与FFSol在房室模型条件下AUC_(0-∞)分别为1 530.55和3 243.338 mg/L·h,半衰期分别为7.533和13.335 h,FFNE的相对生物利用度为211.9%。结果表明,FFNE通过灌胃和肌内注射给药在大鼠体内分布较广,灌胃相对肌内注射吸收差,消除快。将氟苯尼考制成纳米乳剂后促进了氟苯尼考的吸收,氟苯尼考的生物利用度显著提高。     

乳酸菌发酵中药制剂防制鸡球虫病条件的优化及应用

本试验旨在摸索乳酸菌发酵抗鸡球虫中药制剂的最佳制备条件,研究其对鸡球虫病的防制效果。首先对乳酸菌发酵中药制剂的最佳菌株、接菌量、时间、温度、pH条件进行摸索,制得乳酸菌发酵中药制剂,然后选取150只AA+肉鸡进行效果试验。试验随机分为对照组、感染组、乳酸菌发酵组、西药组和纯中药组,21日龄时计算各试验组鸡生长性能及免疫细胞因子IgG、IL-12、IFN-γ、IL-10的含量。结果显示,3.0%戊糖片球菌PP培养于浓度1.0 g/mL的中药培养基,在pH 6.0、37℃的温度下培养12 h,戊糖片球菌PP的活性最高,生长良好;且乳酸菌发酵组鸡的平均日增重显著高于感染组(P<0.05),高于纯中药组及西药组,但差异不显著(P>0.05),与对照组增重效果相当(P>0.05);其料重比(F/G)显著低于感染组(P<0.05),低于纯中药组、西药组,但差异不显著(P>0.05);其IL-12、IFN-γ的表达均显著高于感染组(P<0.05),高于纯中药组和西药组,但差异不显著(P>0.05);其IL-10、IgG显著高于感染组(P<0.05),稍高于纯中药组及西药组(P>0.05)。结果表明经优化的乳酸菌发酵中药制剂可提高感染球虫鸡的生长性能,且能增强机体免疫水平。     

速康解毒口服液在试验大鼠体内药代动力学研究

In order to compare the concentration of each component of Sukang detoxification oral liquid in rat plasma after administrated by oral and intramuscular, and ascertain pharmacokinetic characteristics of Sukang detoxification oral liquid in trials rats, 28 rats were randomly divided into seven groups, using UV spectrophotometry to measure plasma concentration of each component at different times after administrated by oral and intramuscular, calculated pharmacokinetics parameters of various components of detoxification agent. The results showed that plasma concentration-time process of each component of detoxification agent in rats could be described as two-compartment model tools with absorption. After oral administration the maximum plasma concentrations of each component were sodium 8039.455 μg/mL, yeast mannan 129.932 μg/mL, magnesium 3358.328 μg/mL, rhamnose 2296.330 μg/mL.Tp(h) by oral administration of sodium,sulfate,yeast mannan,L-rhamnose were 1.2816,1.4201,1.1337,0.9469 h;by intramuscular administration they were 1.2856,1.4684,1.1079,1.1671 h. Experimental studies had shown that each component of Sukang detoxification oral liquid was quickly absorbed into the blood after administration, there was little difference between oral and intramuscular administrations,but oral administration had long function and more convenient on administration than intramuscular.     

肠炎沙门氏杆菌感染雏鸭脾脏过氧化氢酶及过氧化物酶活性的变化

通过肠炎沙门氏杆菌人工感染雏鸭,探讨肠炎沙门氏杆菌对禽类引发疾病的机理,测定了脾脏组织中POD及CAT活性。结果表明:POD活性较不稳定, 12h显著升高 (P<0.05), 36h、60h呈下降趋势并显著或极显著降低(P<0.05或P<0.01),84h后显著升高(P<0.05);CAT活性呈升高趋势,于 84h时显著高于健康对照组 (P<0.05);用氟苯尼考或中草药复方制剂治疗均可相应增强脾脏POD、CAT的活性。脾脏中CAT和POD参与了抵御肠炎沙门氏杆菌的过程。     

4味中药复方治疗鸡大肠杆菌病效果的研究

为了评价由小鱼眼草、凉粉草、圆穗蓼、梁王茶4味中药组成的方剂抗鸡致病性大肠杆菌的效果，首先对病料进行分离鉴定，然后采用药敏试验测定药物抑菌圈直径，通过小鼠测定中药安全性，最后人工诱发大肠杆菌病模型治疗试验，并应用中药分别以高、中、低3个剂量（1、0.5和0.25 g/mL）对试验鸡进行灌服治疗。结果显示，麦康凯培养基上呈现红色菌落，革兰氏染色镜检见红色短小杆菌；生化鉴定结果显示，葡萄糖、麦芽糖、乳糖、蔗糖、甘露醇、吲哚和MR显阳性，三糖铁产酸产气，枸橼酸盐、VP和硫化氢显阴性。对分离细菌进行PCR检测，检测基因与对照基因均得到大小为1 466 bp的特异性条带。中药、西药环丙沙星抑菌圈直径分别为15.2和18.3 mm。小鼠灌服中药后全部存活，各试验组小鼠平均增重和空白对照组差异不显著（P>0.05），未见不良反应。中药高、中、低3个剂量组、环丙沙星组、感染对照组、空白对照组的存活率分别为96.7%、93.3%、63.3%、93.3%、50.0%和100%，中药高、中、低3个剂量组和环丙沙星组治愈率分别为96.7%、93.3%、63.3%和93.3%。中药高、中剂量组平均增重及胸腺重差异不显著（P>0.05），但显著高于中药低剂量组（P<0.05）；中药高、中剂量组和环丙沙星组脾脏重差异不显著（P>0.05），但显著高于中药低剂量组和感染对照组（P<0.05）。结果表明，1和0.5 g/mL中药口服液抗菌效果明显，与环丙沙星效果相似，中药低剂量效果不明显。     

1株鲤鱼源植物乳杆菌的分离鉴定及其生物学特性分析

【目的】筛选具有优良益生特性的鲤源乳酸菌作为水产养殖用微生态制剂候选菌株。【方法】以鲤鱼肠道内容物及黏膜为菌株的分离来源，采用MRS培养基进行菌株分离纯化，经16S rRNA测序鉴定后，对分离菌株生长特性、产酸能力、耐酸、耐胆盐、抑菌特性、药物敏感性及安全性等生物学特性进行分析。【结果】试验成功分离到1株植物乳杆菌，将其命名为YY001，该分离株在MRS培养基上菌落形态为圆形、表面光滑、边缘整齐、呈乳白色，革兰氏染色为阳性、无芽孢、两端钝圆的短小杆菌；4 h后进入对数期生长，12 h后生长达到稳定期；具有较强的产酸能力，产酸曲线显示，0~12 h pH迅速下降，培养16 h的菌液pH达3.8；在pH 3.0和0.3%胆盐的条件下具有一定耐受性；该分离株对水产常见致病菌柱状黄杆菌、维气氏单胞菌和嗜水气单胞菌均具抑菌效果，且对柱状黄杆菌的抑菌效果最显著，抑菌圈直径达34.19 mm；药物敏感性试验结果显示，分离株对卡那霉素、链霉素和万古霉素耐药；每天一次连续1周灌胃10⁸CFU分离菌株对小鼠无毒害作用。【结论】本研究分离到的菌株YY001具有优良的生物学特性，可作为水产养殖用微生态制剂候选菌株，为后续制备鲤鱼用微生态制剂奠定基础。     

基于网络药理学研究丹参-川芎抗脑缺血再灌注损伤作用机制及试验验证

【目的】 通过网络药理学研究丹参-川芎药对治疗缺血性脑卒中的有效性成分及相应基因靶标，探讨其作用机制。【方法】 应用中药系统药理学计数平台（TCMSP）、GeneCards、OMIM数据库，筛选出丹参-川芎药对治疗缺血性脑卒中的潜在靶点并进行GO功能和KEGG通路富集分析。分别设置假手术组、模型组、丹参-川芎低、中、高剂量组，采用预防和治疗给药方式对线栓制备的脑缺血再灌注模型大鼠进行干预，采用Zea-longa评分法对脑缺血再灌注24 h模型大鼠进行神经功能评分，苏木素-伊红（HE）染色法观察脑组织病理学变化进行初步验证。【结果】 本研究共筛选到丹参-川芎药对主要有效活性成分共72个，其中川芎7个，丹参65个，缺血性脑卒中的靶点基因1 972个，有效活性成分与缺血性脑卒中共同作用靶标94个，包括IL6、IL10、TNF、MMP9、VEGFA、CASP3等；GO功能和KEGG通路富集结果提示，丹参-川芎药对治疗缺血性脑卒中与PI3K-Akt、cGMP-PKG、VEGF等多个信号通路有关。动物试验结果表明，丹参-川芎可减轻脑组织病理改变，减轻神经功能缺损，改善脑缺血再灌注损伤。【结论】 丹参-川芎药对可能是通过PI3K/Akt信号通路改善脑缺血再灌注损伤，发挥抗细胞凋亡的作用。     

Pharmacokinetics of voriconazole after single dose intravenous and oral administration to alpacas

Voriconazole is a new antifungal drug that has shown effectiveness in treating serious fungal infections and has the potential for being used in large animal veterinary medicine. The objective of this study was to determine the plasma concentrations and pharmacokinetic parameters of voriconazole after single-dose intravenous (i.v.) and oral administration to alpacas. Four alpacas were treated with single 4 mg/kg i.v. and oral administrations of voriconazole. Plasma voriconazole concentrations were measured by a high-performance liquid chromatography method. The terminal half-lives following i.v. and oral administration were 8.01 ± 2.88 and 8.75 ± 4.31 h, respectively; observed maximum plasma concentrations were 5.93 ± 1.13 and 1.70 ± 2.71 μg/mL, respectively; and areas under the plasma concentration vs. time curve were 38.5 ± 11.1 and 9.48 ± 6.98 mg·h/L, respectively. The apparent systemic oral availability was low with a value of 22.7 ± 9.5%. The drug plasma concentrations remained above 0.1 μg/mL for at least 24 h after single i.v. dosing. The i.v. administration of 4 mg/kg/day voriconazole may be a safe and appropriate option for antifungal treatment of alpacas. Due to the low extent of absorption in alpacas, oral voriconazole doses of 20.4 to 33.9 mg/kg/day may be needed.     

益母黄丹口服液的制备工艺研究

确定益母黄丹口服液的制备工艺条件并建立质量标准。采用正交试验法,对益母黄丹口服液的提取制备工艺条件进行优化,并采用紫外分光光度法,以盐酸益母草碱为对照品,在277 nm处测定按照不同工艺制备的口服液中盐酸益母草碱含量,再采用薄层色谱法对口服中益母草、黄精进行定性鉴别进行质量控制。结果表明,口服液最佳制备工艺为煎煮时间1.5 h,煎煮3次,醇沉分数50%;紫外分光光度法能测定口服液中益母草碱含量、薄层色谱中益母草、黄精斑点清晰,阴性对照无干扰。本试验制备工艺的方法简单可行,建立的质量标准适用于益母黄丹口服液的质量控制。     

双黄连可溶性粉不同组分抗菌抗病毒活性研究

为了深度开发双黄连可溶性粉（金银花、连翘、黄芩，1：1：2），并为家禽、家畜合理选择用药提供科学依据，本研究以双黄连口服液生产工艺生产的双黄连可溶性粉及其醇沉物（多糖组分）、滤液（黄酮组分）作为研究材料，以哺乳动物牦牛源轮状病毒、鸡新城疫病毒，牦牛源致病性大肠杆菌、沙门氏菌、金黄色葡萄球菌为研究对象，采用牛津杯结合平板二倍稀释法，探讨其体外抗菌活性；以牦牛MA-104细胞株、鸡胚成纤维细胞株UMNSAH/DF-1为宿主细胞，采用噻唑蓝比色法（MTT）和细胞病变（CPE）检测法，探讨其体外抗病毒活性。研究结果表明，双黄连可溶性粉对革兰氏阴性菌（牦牛源大肠杆菌、牦牛源沙门氏菌、大肠杆菌质控菌株）的抑菌效果优于对革兰氏阳性菌（牦牛源金黄色葡萄球菌、金黄色葡萄球质控菌株）的抑菌效果，从双黄连可溶性粉中分离的黄酮组分可能是双黄连可溶性粉抑菌的主要成分，而多糖组分则无抑菌活性；黄酮组分对革兰氏阳性菌的抑菌效果优于对革兰氏阴性菌的抑菌效果；双黄连可溶性粉及其黄酮组分和多糖组分对鸡胚胎成纤维细胞UMNSAH/DF-1的最小无毒浓度（TC₀）分别为：2.58、1.17和1.56 μg/mL，对牦牛细胞MA-104的TC₀分别为：1.290、0.585和0.780 μg/mL，对牦牛轮状病毒均具有良好的抗病毒效果，双黄连可溶性粉对鸡新城疫病毒的抗病毒效果优于黄酮和多糖组分。研究结果为双黄连可溶性粉深度开发和对畜禽合理选择用药提供了科学依据。     

Disposition of flunixin meglumine injectable preparation administered orally to healthy horses

An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.     

牛至油博落回口服液的研制及体外抑菌活性测定

【目的】 研制牛至油博落回口服液, 并测定其体外抑菌活性及其主要成分的联合抑菌效果, 为临床用药提供理论依据。【方法】 通过预试验和Box-Behnken响应面法优化处方; 采用高效液相色谱法测定口服液主要成分含量; 采用滤纸片法测定口服液对大肠杆菌、沙门氏菌、金黄色葡萄球菌和粪链球菌的抑菌圈直径; 采用试管二倍稀释法测定口服液、5%牛至油溶液及1%博落回溶液对4种细菌的最小抑菌浓度(MIC)和最小杀菌浓度(MBC); 采用微量棋盘稀释法对5%牛至油溶液与1%博落回溶液进行体外联合药敏试验。【结果】 牛至油博落回口服液最优配方为: 5%牛至油, 1%博落回提取物, 25%增溶剂聚氧乙烯(40)氢化蓖麻油, 0.02%抗氧化剂2, 6-二叔丁基对甲酚(BHT), 余量为水。口服液中香芹酚的含量为42.59 mg/mL, 血根碱含量为6.51 mg/mL。口服液对4种菌的抑菌圈直径分别为16.9、16.4、23.7和17.0 mm, MIC分别为3.125、3.125、1.5625和1.5625 μL/mL, MBC分别为12.5、6.25、3.125和3.125 μL/mL; 5%牛至油溶液对4种菌的MIC分别为25、12.5、6.25和100 μL/mL, MBC分别为100、50、25和>200 μL/mL; 1%博落回溶液对4种菌的MIC分别为6.25、12.5、3.125和6.25 μL/mL, MBC分别为50、25、6.25和25 μL/mL。联合药敏试验表明, 二者联合用药对大肠杆菌、沙门氏菌起相加作用, 对金黄色葡萄球菌无作用, 对粪链球菌为协同作用。【结论】 试验制备了牛至油博落回口服溶液剂, 该制剂对大肠杆菌、沙门氏菌、金黄色葡萄球菌和粪链球菌具有良好抑制作用。     

Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and oral administration in goats

Summary

The intravenous and oral pharmacokinetics of an amoxicillin and clavulanic acid combination (20 mg/kg of sodium amoxicillin and 5 mg/kg of potassium clavulanate) were studied in six goats. After intravenous administration the pharmacokinetics of both drugs could be described by an open two‐compartment model. Amoxicillin had a greater distribution volume (0.19 ± 0.01 l/kg) than clavulanic acid (0.15 ± 0.01 l/kg), whereas the distribution and elimination constants were higher for the latter, which was eliminated more quickly than amoxicillin. After oral administration of both drugs their pharmacokinetic behaviour was best described by an open one‐compartment model with first‐order absorption. Elimination half‐lives were twice as long after oral (2.15 ± 0.20 h and 1.94 ± 0.16 h for amoxicillin and clavulanic acid respectively) than after intravenous administration (1.20 ± 0.16 h and 0.86 ± 0.09, respectively). An apparent ‘flip‐flop’ situation was evident in this study. Bioavailability was 27% for amoxicillin and 50% for clavulanic acid.     

植物乳杆菌和短乳杆菌复合添加对高丹草青贮效果的影响

为研究不同乳酸菌互作对高丹草(Sorghum bicolor×Sorghum sudanense)青贮效果的影响,将前期筛选的植物乳杆菌(Lactobacillus plantarum)和短乳杆菌(L.brevis)按不同比例(1 ∶ 0(LP06),0 ∶ 1(LBR02),4 ∶ 1(F-1),3 ∶ 2(F-2)...     

银黄颗粒中黄芩甙在大鼠体内的测定及药代动力学

目的：考察银黄制剂的药动学特征。方法：建立测定大鼠血浆中黄芩甙的高效液相色谱法（HPLC）,并以银黄颗粒为代表进行药代动力学研究。结果：黄芩甙经直肠灌注比灌胃血药浓度高、消除速率慢;黄芩甙经灌胃会产生首过代谢作用,同时在用药后约600min出现双峰现象;银黄颗粒中的黄芩甙受其它成分的影响不明显,在大鼠体内的药动学过程与单体黄芩甙基本一致。结论：用建立的HPLC法进行银黄颗粒的药代动力学研究,方法简单、准确、快速。并且获得的药代动学参数具有一定临床应用价值。     

The pharmacokinetics and bioavailability of acepromazine in the plasma of dogs]

Acepromazine is extensively used in veterinary practice. In dogs, it is used mainly as a preanaesthetic and sedative agent, without the knowledge of pharmacokinetic data in this species. We studied the disposition both after oral and intravenous administration. It was shown, that the sedative effect after an oral dose of 1.3-1.5 mg/kg lasted for about 4 hours. The elimination was slower after oral administration (half-life 15.9 h) than after i. v. injection (half-life 7.1 h). The bioavailability of the orally administered drug formulation averaged 20%. The calculation of the pharmacokinetic parameters was performed computer-aided, using conventional compartmental analysis and non-compartmental statistical moment analysis and the results were compared.     

喹烯酮在鸡体内的代谢及药物动力学研究

以HPLC-MS/MS为定量手段,研究了喹烯酮经静脉注射(2.5 mg/kg)、口服(30 mg/kg)两种给药途径在鸡体内的代谢及药物动力学特征.鸡静脉注射喹烯酮后,血浆中检测到喹烯酮原药和1-脱氧喹烯酮;口服灌注喹烯酮后,血浆中检测到喹烯酮原药和3-甲基喹噁啉-2-羧酸(MQCA).喹烯酮在鸡体内的药动学数据采用统...     

Effect of dietary fat on oral bioavailability of tepoxalin in dogs

A pharmacokinetic study was conducted to compare the oral bioavailability of tepoxalin and its pharmacologically active acid metabolite in fasted dogs and dogs fed either a low-fat or high-fat commercial diet. Using a cross-over design, six beagles were administered tepoxalin (10 mg/kg) intravenously (i.v.) and orally (p.o.) after being fed one of three diets (fasted, low-fat, or high-fat). Thereafter, blood samples were collected at frequent intervals, concentrations of tepoxalin and acid metabolite in plasma were determined by high performance liquid chromatography, and pharmacokinetic parameters were estimated. After i.v. dosing, the mean (+/-SD) half-life of elimination (t(1/2(beta))) was 2.45 +/- 1.47 h. After p.o. administration, plasma concentrations of acid metabolite were consistently higher than corresponding concentrations of the parent tepoxalin, indicating that tepoxalin is subject to a substantial first-pass effect. Mean (+/-SD) peak concentrations of tepoxalin were significantly higher after feeding of low-fat (1.08 +/- 0.37 microg/mL) and high-fat (1.19 +/- 0.29 microg/mL) diets than in fasted dogs (0.53 +/- 0.20 microg/mL), suggesting that feeding improves oral bioavailability.     

Effect of Fermented Traditional Chinese Medicine on Preventing and Treating Colibacillosis and Immune Regulation in Broilers

This study was aimed to evaluate the efficacy of the fermented traditional Chinese medicine on treating colibacillosis and immune regulation in chickens.240 healthy 1-day-old AA White-feathered broilers were selected to carry out the control test of Escherichia coli O78 LD₅₀ and compound Chinese medicine fermentation broth on colibacillosis.The therapeutic effect was evaluated at 28 days old,and the immune organ index,antioxidant index and intestinal flora were measured at 28 and 42 days old.The results showed that the infection time of Escherichia coli was delayed from 4 to 24 h after the treatment of fermentation liquid of traditional Chinese medicine fermented by Lactobacillus plantarum and Bacillus subtilis.The effective rates of high dose group (1.0 g/mL),medium dose group (0.5 g/mL) and antibiotic group (neomycin sulfate) were 80.0%,76.7% and 80.0%,and the cure rates were 80.0%,70.0% and 70.0%,respectively.Compared with infection and antibiotic groups,the thymus index and bursa index in high dose group at 28 days old were increased by 165.6%(P<0.05),25.4%(P>0.05) and 82.6%(P<0.05),94.3% (P<0.05),respectively.The thymus index and bursa index at 42 days old were increased by 97.4%,82.0% and 43.4%,27.5% (P<0.05),respectively.The T-AOC,TP,GSH-Px and T-SOD antioxidant indexes were significant difference (P<0.05),and significantly increased the content of lactic acid bacteria in intestine and reduced the content of Escherichia coli at 28 and 42 days old (P<0.05).In conclusion,the medium dose group of fermented traditional Chinese medicine (0.5 g/mL) had obvious antibacterial effect and provided substitute for antibiotics,the high dose group of fermented traditional Chinese medicine (1.0 g/mL) was significantly better than antibiotics for broilers.