Pharmacokinetic study of an injectable long-acting parenteral formulation of doxycycline hyclate in calves

Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically sound. A poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its s.c. injection to calves. Serum concentrations profiles for such a prepartion were compared to the corresponding profiles obtained with an aqueous formulation of DOX-h injected either i.m. or i.v. in 10 calves in a crossover study at dose of 10mg/kg, with washout periods. DOX-h-LA showed the greatest values for bioavailability (602%); maximum serum concentration (C(max)) value was 1.99microg/mL with a time to reach C(max) (T(max)) of 25h and an elimination half-life of 40.81h. Considering minimum effective serum concentration of 0.5microg/mL a dose-interval of 80h can be achieved for DOX-h-LA, and only 9.7h and 17h after the i.v. or i.m. administration of DOX-h, respectively.     

葡萄糖基聚合物的酶催化合成及其在制备缓释微球中的应用

以脂肪酶Novozym-435催化葡萄糖和10- 十一碳烯酸合成了6-O-（10- 十一碳烯酸）-葡萄糖酯，在K2S2O8引发下合成了葡萄糖基聚合物。采用复凝聚法以葡萄糖基聚合物和海藻酸钠为基质材料，将非诺洛芬钙包裹制成缓释微球。通过L9（3^4）正交实验得出微球的最佳制备工艺条件，结果是葡萄糖基聚合物：海藻酸钠质量比=1：2，pH3.0，搅拌速度400r／min，反应成球温度45℃。在最佳工艺条件下制备的非诺洛芬钙缓释微球，粒径范围是10-20μm，平均药物包封率（73.74±3.12）％。同时，体外溶出试验表明，该微球具有较好的缓释作用。     

Experimental study of 5-fluorouracil loaded polylactic acid nanoparticles control-releasing preparation on tumor

AIM: To investigate the preparation techniques and anti-tumor effects both in vitro and in vivo of a novel nanoparticles control-releasing preparation of 5-fluorouracil (5-FU) by intravenous injection.METHODS: With polylactic acid (PLA) as marix materials,we adopted ultrasound emulsification method to prepare PLA enveloped 5-FU nanoparticles (5-FU-NPs).Scanning electricity microscopy was used to observe the morphology of 5-FU-NPs and laser optical scattering experiment was conducted to determine its diameter distribution.The drug-carrying capacity (ratio) of the nanoparticles was determined by means of high-power liquid chromatography(HPLC) and MTT test was used to observe cytotoxicity in vitro.The anti-tumor effects were determined at different dosages,frequencies of taking drugs in vivo.RESULTS: Scanning electron microscopy showed that the 5-FU-NPs were globular particles with smooth surface in an average particle diameter of 191.9 nm with a normal distribution,and the drug-carrying capacity of 5-FU-NPs was 15.2%.5-FU-NPs had the same anti-cancer effect as unenveloped drug in vitro and showed typical dose-effect relationship.Compared to naked 5-FU,5-FU-NPs presented significant difference (P<0.05) in anti-cancer effect.CONCLUSION: Nanoparticles may serve as effective carrier for controlled release of 5-FU,which lead to reasonable administration of 5-FU with less toxicity.     

猪用生长激素脂质体对小鼠的促生长作用

[目的]研究猪用生长激素（porcine somatotropin,PST）脂质体对小鼠的促生长作用与缓释效果。[方法]将试验小鼠随机分组,试验组小鼠分别腹腔注射PST纯品和PST脂质体,对照组腹腔注射生理盐水。分别于7、14和28 d后称重,计算小鼠增重率。[结果]试验组小鼠增重与对照组差异显著（P〈0.05）,表明PST和PST脂质体对小鼠有促生长作用,且PST脂质体具有明显的缓释效果。[结论]PST脂质体缓释期长达7 d以上,具有显著的促生长效果。     

替米考星微囊的体外释放特性考察

采用篮法考察替米考星微囊在磷酸盐缓冲液(pH=6.8)中的释放特性,并与市售制剂进行比较;进而对替米考星微囊的释药模型进行拟合。结果表明,1 h时,市售替米考星微囊中的药物几近释放完全,而自制替米考星微囊样品1、2和3的药物累积释放率分别为35％、50％和26％。4 h时,样品1和样品2的药物也已经基本释放完全(约90％);而样品3的药物累积释放率才达到50％。模型拟合结果表明,自制替米考星微囊的体外释药曲线与Ritger-Peppas方程拟合度最好,样品1和样品3的拟合方程分别为lnQ = 0.543 6lnt-0.949 4(R2=0.9991)和lnQ = 0.539 1lnt-1.387 6(R2 =0.997 3)。由此可见,自制的替米考星微囊表现出一定的缓释作用,而且药物释放符合Ritger-Peppas方程。     

黄芩苷缓释微囊的研制研究

[目的]制备黄芩苷缓释微囊,设计并优化处方,初步制定该制剂的质量标准。[方法]采用复凝聚法,以明胶和阿拉伯胶为囊材,黄芩苷为囊心物,吐温-80为润湿剂制备缓释微囊。以包封率作为主要质量判定指标,通过单因素考察和正交试验优化处方工艺。借助显微镜和电镜观察微囊形态;采用紫外分光光度法进行含量测定;以水为溶出介质考察该制剂的体外溶出情况;。[结果]最优处方是明胶和阿拉伯胶浓度皆为13.3 mg/ml,反应温度为50℃,pH为3.90,材药比为5∶1。按该处方制得的微囊囊形圆整光滑,载药量较高。[结论]复凝聚法可成功制备出包封率较高的黄芩苷缓释微囊,且产品稳定性良好。该法可操作性强,重复性好,有一定的实用价值。     

微胶囊技术在缓释香味刨花板制备中的应用

制备薰衣草、茉莉花及迷迭香精油香精微胶囊,采用SEM观察表面形貌并测定香精微胶囊的包埋率及100℃焙烘留香期,发现选用薰衣草精油制备的微胶囊呈现流动性均匀粉状,具有良好的形貌特征,有更高的包埋率和更长的留香期,较茉莉花及迷迭香更适合制备芳香型刨花板。确定薰衣草微胶囊刨花板制造优化工艺参数为:施香量4.5%、施胶量15%、热压温度170℃、热压时间11min,制备出具有缓释芳香气味刨花板,其物理力学性能满足GB/T4897.3—2003规定要求。     

海藻酸钠-HCG制剂对雌性金鱼(Carassius auratus)生殖激素水平的影响

采用海藻酸钠(Na Alg)-HCG缓释制剂进行激素埋植实验。实验开始时,雌性金鱼(Carassius auratus)卵母细胞处于Ⅲ期。实验期间记录雌性金鱼性腺发育、放免(RIA)法测定血清性激素含量并且通过RT-PCR检测激素相关基因表达。结果表明,埋植Na Alg-HCG缓释激素后,雌性金鱼性成熟系数(GSI)在6-21 d显著高于对照组,血清睾酮(T)和雌二醇(E2)水平在6-30 d显著高于对照组;性腺芳香化酶基因(CYP19A基因)和雌激素受体基因(ERα基因)m RNA相对表达量分别在2-21 d、14-30 d内显著高于对照组,其性腺GH基因m RNA相对表达量变化不显著。研究结果显示,一次性埋植Na Alg-HCG缓释制剂,与雌性金鱼繁殖相关的生物学指标、激素水平、基因表达量较对照组产生明显变化,同时这种缓释制剂可以作为埋植激素的载体。     

Self-assembly,Mixed System and Drug-loading Research of Rosin-based Tertiary Amine Salt北大核心CSCD

A novel maleic rosin-based ester tertiary amine salt surfactant (RETAS) with three hydrophilic groups was synthesized through D-A addition reaction, acyl chlorination, esterification reaction and salt forming reaction with rosin acid as raw material. The critical micelle concentration (CCMC) of RETAS was 0.73 mmol/L (0.50 g /L), and the corresponding surface tension at CMC (γCMC) was 38.58 mN/m. The RETAS was mixed with natural soapnut saponin. The best compound proportion of mixed system was obtained by determining the surface tension, emulsification property and foam property to study the synergistic effect. And the self-assembly behavior and micelle morphology of the composite system was characterized by transmission electron microscopy (TEM) and the micelle formation mechanism was speculated in detail. The results showed that the γCMC and CCMC of mixtures were 37.57 mN/m and 0.40 g/L when the optimum mass ratio of RETAS/soapnut saponin was 5:5. The emulsifying properties of RETAS and saponin were only 292 s and 310 s respectively, but the emulsifying properties increased to 373 s in the optimum mass ratio. Finally, the cytotoxicity of RETAS on human colon adenocarcinoma cells (Caco-2) was investigated and it was found that it had non-toxic or low toxicity and was applied to study the drug loading properties of anticancer drug doxorubicin (DOX). The release rates of DOX on RETAS were 67 % and close to 100 % in pH value 7.4 and 5.0, respectively. While the release rates of DOX on the mixture were 68 % and close to 90 % in pH value 7.4 and 5.0. The results showed that both RETAS and mixed product could be used as the target carrier of DOX. Under simulated tumor conditions, DOX was still slowly released after 24 hours in pH=5.0. © 2018, Editorial Board of «Chemistry and Industry of Forest Products». All right reserved.     

Pharmacokinetics of Tramadol and its Metabolites M1, M2 and M5 in Horses Following Intravenous, Immediate Release (Fasted/Fed) and Sustained Release Single Dose Administration

Tramadol (T) is a centrally acting analgesic structurally related to codeine and morphine. This drug displays a weak affinity for the μ and δ-opioid receptors, and weaker affinity for the κ-subtype; it also interferes with the neuronal release and reuptake of serotonin and noradrenaline in the descending inhibitory pathways. The metabolism of this drug has been investigated in different animals (rats, mice, Syrian hamsters, guinea pigs, rabbits, and dogs) and humans; similar metabolites are produced but in different amounts. The major metabolic pathways involved in phase I metabolite production (M1–M5) are O-demethylation, N-demethylation, and N,N-demethylation. The aim of the current study is to evaluate the pharmacokinetic profile of T in the horse, and its M1, M2, and M5 metabolites after single-dose administration (5 mg/kg body weight [BW]) by intravenous, sustained-release tablets and immediate-release capsules. We also will investigate the potential effects of fasting and feeding on bioavailability of immediate-release capsules. The study design was divided into four randomized phases. Twenty-four gelding Italian trotter race horses were divided into four groups (6 animals each) and administered T intravenously, with T immediate-release capsules in a fasting status, T immediate-release capsules in a feeding status, and T sustained-release in fasting status. Blood samples were collected at different times and analyzed by high-pressure liquid chromatography (HPLC) with fluorimetric detection. The limit of quantification was 5 ng/ml for T, M1, and M2, and 10 ng/ml for M5. A one-compartment model best fit the plasma concentrations of T and M2 after all treatments. Unfortunately, for M1 and M5, it was not always possible to fit plasma curves because of very low and variable concentrations. M2 was the main metabolite produced in the four different treatments and its concentration was higher than the concentration of T after sustained-release administration. Conversely, M1, the main metabolite in humans, and M5 seemed to be only marginally produced in the horse. When T was administered in both fasted and fed states, variations in some pharmacokinetic parameters were not considered clinically significant. We concluded that T could be administered in either a fasted or a fed condition.