紫杉醇-姜黄素介孔SiO_2/脂质复合递药系统体外释药研究

为了考察自制紫杉醇-姜黄素介孔SiO_2/脂质复合递药系统的体外释药行为,建立高效液相色谱法同时检测紫杉醇-姜黄素浓度;筛选适当增溶剂增加紫杉醇-姜黄素溶解度;反透析法考察各药物组的体外释药行为,绘制紫杉醇-姜黄素累积释药曲线并进行释药模型拟合。结果显示,不同药物组中紫杉醇-姜黄素释药行为表现出一定差异性,两种药物单药组累积释药量均高于混合组,自制递药系统累积释药量均高于裸药组。但紫杉醇不同递药系统组累积释药量由高到低分别为:MSNs>PLMSNs>LMSNs,姜黄素不同递药系统组累积释药量由高到低分别为:LMSNs>PLMSNs>MSNs。此外,PLMSNs组中紫杉醇-姜黄素释药行为均符合Hixon-Crowell释药模型。     

替米考星微丸肠溶包衣的处方筛选

采用挤出滚圆方法制备替米考星载药丸芯,以丙烯酸树脂Ⅱ和Ⅲ为材料利用离心造粒包衣设备对丸芯进行包衣。结果显示,所制备的替米考星肠溶微丸在pH=1盐酸溶液中2 h内累积释放度小于10%,用0.2 mol/L的磷酸钠溶液将溶出介质pH调至6.8,继续运转45 min后累积释放度达80%以上,符合《中国药典》对肠溶制剂的要求。     

两种液中干燥法制备盐酸多西环素微囊的比较研究

分别用水中干燥法和油中干燥法制备盐酸多西环素微囊,比较各自制得的微囊质量参数及其体外释药特性,以期为盐酸多西环素缓释制剂提供科学依据.以乙基纤维素为囊材,通过正交设计分别考察各因素对微囊质量的影响,评定微囊的大小、形态、载药量、包封率等质量指标,以释放度实验研究其释药特性.结果显示,水中干燥法所制得微囊粒径20 ～ 30 μm,包封率为87.3％;油中干燥法微囊粒径范围为200～400μm,包封率为93.7％.上述结果表明油中干燥法所得微囊粒径较大,包封率、载药量均明显高于水中干燥法制得的微囊;体外释药实验表明,微囊化大大延缓了盐酸多西环素的释放时间.     

离子色谱法测定磷酸替米考星中磷酸根含量

建立离子色谱法测定磷酸替米考星中的磷酸根含量,并考察替米考星与磷酸的成盐比率。方法:色谱柱为ASLL-HC阴离子交换柱(250 mm×4 mm),检测器为电导检测器,流动相为30 mmol/L氢氧化钠溶液,流速为1.0 m L/min,柱温为30℃,进样体积为25μL。结果:磷酸根离子的检测限与定量限分别为0.002μg/m L、0.006μg/m L,在0.1~4.0μg/m L范围内线性关系良好(R2=0.9991),精密度良好(RSD=1.04%,n=8),平均回收率为99.11%(RSD=0.33%,n=9)。磷酸替米考星中替米考星与磷酸的成盐率约为1∶1。结论:所建立的离子色谱法专属性强、精密度好、准确度高,可用于磷酸替米考星的磷酸根含量与成盐率测定,5批磷酸替米考星样品的成盐状态良好。     

阿维菌素缓释明胶微囊制备工艺及其体外释药特性

以生物可降解材料明胶为囊材,采用单凝聚法制备了阿维菌素明胶微囊,通过L9(34)正交试验设计,对微囊制备工艺进行了优选,所得微囊粒径在2～70μm,其中20～50μm的占78%.药物包封率为(87.61±1.41)%,载药量为(15.77±0.23)%.体外释药试验,微囊释药符合一级动力学特征,t1/2=9.2d,比原药提高5.4倍,表明所制备的明胶微囊具有一定的缓释药物效应.     

替米考星长效混悬剂的研制与质量评价

[目的]利用现代缓释技术,以替米考星为原料药,研制出溶解度较高、疗效强、可减少给药次数的替米考星长效混悬剂,并对其进行质量评价,为该药的批量生产提供可靠依据。[方法]通过正交优化法选择最优处方,并对最优处方进行含量测定试验、稳定性试验和药动学试验。[结果]替米考星长效混悬剂最佳处方为:替米考星原料药2.5g/100 mL,有机溶媒(1,2-丙二醇:乙醇=9:1)占比65%,润湿剂(吐温-80)0.3%,助悬剂(羟丙甲纤维素)5%,抗氧剂(无水亚硫酸钠)0.03%;含量测定结果为合格;影响因素试验发现替米考星长效混悬剂对高温和强光照敏感,对湿度不敏感;加速试验和长期试验发现替米考星长效混悬剂稳定性良好;药动学试验发现替米考星长效混悬剂和实验室自制替米考星溶液的AUC分别为43.164 9μg·h·mL~(-1)和26.206 5μg·h·mL~(-1),替米考星长效混悬剂的相对生物利用度为164.71%。[结论]本试验制得的替米考星长效混悬剂含量合格、稳定性良好、相对生物利用度高,可以批量生产,用于大型养殖场的大规模给药。     

复方替米考星可溶性粉在鸡体内的药动学研究

本研究比较了口服复方替米考星可溶性粉与单独肌注替米考星注射液和静注磺胺二甲嘧啶钠注射液在鸡体内药物代谢动力学特征和相对生物利用度。36只健康鸡,随机分为3组,给药剂量均为20 mg/kg,翼下静脉采血,高效液相色谱法检测鸡血浆中的药物浓度。采用药动学软件Win Nonlin 6.1的非房室模型分析方法,计算出药物的动力学参数。鸡口服复方替米考星可溶性粉、肌注替米考星注射液和静注磺胺二甲嘧啶钠注射液后的药时曲线下面积(AUC)分别为:9.49±3.64、37.17±10.82、12.40±4.11、61.31±11.38μg×h/m L。复方替米考星可溶性中替米考星相对于肌肉注射的替米考星的生物利用度为75.98%,复方制剂中磺胺二甲嘧啶钠的绝对生物利用度为60.63%。复方替米考星可溶性粉和单方药物相比,药动学参数经t检验,t_(1/2)、T_(max)、C_(max)、AUC、MRT等存在显著性差异(P0.05)。结果表明复方替米考星可溶性粉单剂量口服给药吸收较慢,达峰时间显著延迟,平均驻留时间显著延长,有利于抗菌作用的发挥。     

替米考星固体分散体的制备与物相鉴定

为改善替米考星的水溶性，提高其生物利用度，试验选用聚乙二醇6000和泊洛沙姆188作为载体，采用熔融法制备替米考星固体分散体。以体外累积溶出度为评价指标，通过正交试验筛选最佳制备工艺，选用X-射线衍射法、傅里叶红外光谱法、扫描电镜法进行物相鉴定。结果显示，替米考星固体分散体最佳制备工艺为联合载体PEG6000：P188=20:1、药载比1:3、搅拌时间1 h、固化时间12 h；物相鉴定表明，替米考星为非晶态，固体分散体为晶体结构，替米考星以无定形态分散于载体中；替米考星固体分散体在2 min时溶出度达到71.8%，15 min时完全溶解，显著提高了替米考星的溶出速率。该制备工艺简单，选用联合载体制备替米考星固体分散体，能够有效避免单一载体制备替米考星固体分散体出现的缺陷，有效提高溶出度，方便临床饮水用药。     

替米考星脂质体的制备及体外释放度的研究

目的 研究替米考星脂质体的制备工艺以及体外释放。方法 以pH梯度法制备替米考星脂质体,以包封率为指标优化其制备工艺,观测其形态、粒径和Zeta电位,并进行体外释放实验。结果 电子显微镜下可见多层囊状脂质体,测得三批替米考星脂质体的平均包封率为96.93％,平均粒径112.3 nm,平均Zeta电位为+9.9 mV,体外释放符合一级动力学方程释放规律。结论 替米考星脂质体制备工艺简单、包封率高、成型良好,体外释放具有明显的缓释效果。     

生物降解型吡喹酮微囊的构建及其药剂学性质的研究

以生物可降解的明胶和阿拉伯胶为囊材 ,采用复凝聚法制得适合肌肉注射的吡喹酮微囊 ;考察其形态学特征及吡喹酮微囊的体外动态与静态释药情况。建立高效液相紫外色谱测定微囊内药物含量。结果 3批生物降解型吡喹酮微囊显微镜下和电镜下外观均一、光滑 ,平均载药量为 10 .0 3%,平均包封率为 6 1.75 %,平均粒径为45 .1μm;体外释药研究结果表明微囊内的药物无突释现象。该生物降解型吡喹酮微囊可达到缓慢释放和长效制剂的基本要求。     

Phase I evaluation of CCNU (lomustine) in tumor-bearing cats

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor-bearing cats. Response data were obtained when available. Twenty-five cats were treated with CCNU at a dosage of 50-60 mg/m3 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose-limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6-week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14-21 days after treatment. The median platelet count at the nadir was 43,500 cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50-60 mg/m3 every 6 weeks.     

Furosemide continuous rate infusion in the horse: evaluation of enhanced efficacy and reduced side effects

Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically significant difference in urine volume over 24 hours between methods; however, urine volume was significantly greater after CRI compared with IA during the first 8 hours ([median 25th percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0] for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma volume, and suppressed renal concentrating ability throughout the infusion period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133 mmol [1.110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus 73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2.378] versus 1,596 mmol [1,457, 1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve was 1,285.7 and 184.2 mL x mg/mL for CRI and IA, respectively. Furosemide CRI (0.12 mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended when profound diuresis is needed acutely in horses.     

The Epidemiology of Gastrointestinal Nematodes of Dairy Cattle in Central Kenya

The epidemiology of H. placei and of other gastrointestinal nematodes in yearling dairy cattle was examined on two farms in Kiambu District, central Kenya during each of 13 one-month periods from April 1993 to April 1994. On each farm, 32 newly weaned dairy calves were given a single dose of albendazole and then placed on experimental pastures. Twelve of the animals were designated for bi-monthly slaughter (n = 2) and analysis of worm population characteristics and 20 were designated for blood and faecal collection and for weighing. Two parasite-free tracer calves were grazed alongside the weaner calves each month throughout the study period and were also slaughtered for analysis of worm populations. Faecal egg counts, haematological and serum pepsinogen determinations, herbage larval counts, and animal live weight changes were recorded monthly. The study revealed that Haemonchus placei, Trichostrongylus axei, Cooperia spp. and Oesophagostomum radiatum were responsible for parasitic gastroenteritis and that H. placei was the predominant nematode present in the young cattle on both farms. Faecal egg counts from resident cattle and necropsy worm counts revealed that pasture larval levels were directly related to the amount of rainfall. The total worm burdens in the animals were highest during the rainy season (March–June and October–December) and lowest during the dry seasons (July–September and January–February). The very low recovery of immature larvae of H. placei from the tracer calves indicated that arrested development is not a feature of the life cycle of this parasite in central Kenya. The maintenance of the parasite population depended on continuous cycling of infection between the host and the pasture. The agroclimatic conditions of the study area were such that, in general, favourable weather conditions for the development and survival of the free-living stages of gastrointestinal nematodes existed all year round.     

Diversity of Ectoparasites in Sheep Flocks in Sa~o Paulo,Brazil

The occurrence of ectoparasites in sheep flocks is frequently reported but seldom quantified. Sheep production used to be a predominantly family activity in the state of Sa~o Paulo (Brazil), but it began to become a commercial activity in the past decade. Thus, information about the ectoparasites existing in sheep flocks has become necessary. The present data were obtained by means of questionnaires sent to all sheep breeders belonging to the `Associaça~o Paulista de Criadores de Ovinos' (ASPACO; Sa~o Paulo State Association of Sheep Breeders). Response reliability was tested by means of random visits paid to 10.6% of the respondents. Most of the properties (89.5%) reported the presence of one or more ectoparasites. Screw-worm (Cochliomyia hominivorax) was the most frequent ectoparasite (72.5%), followed by bot fly larvae (Dermatobia hominis, 45.0%), ticks (Amblyomma cajennense) and Boophilus microplus, 31.3%) and finally lice (Damalinia ovis, 13.8%). Combined infestations also occurred, the most common one being screw-worm with bot fly larvae (36.0%) followed by bot fly larvae with ticks (13.9%), screw-worm with ticks (9.3%), bot fly larvae with lice (6.9%), and ticks with lice (5.0%). The most common triple combination was screw-worm, bot fly larvae and ticks (12.8%). Breeds raised for meat or wool were attacked by bot fly larvae and ticks more often than other breeds. Lice were only absent from animals of indigenous breeds. The relationships among these ectoparasites are discussed in terms of sheep breeds, flock size, seasonality and the ectoparasitic combinations on the host.     

Evaluation of biohydrogenation rate of canola vs. soya bean seeds as unsaturated fatty acids sources for ruminants in situ

An experiment was conducted to study disappearance of C14 to C18 fatty acids, lag times and biohydrogenation (BH) rates of C18 fatty acids of ground soya bean and canola seeds in situ. Three ruminally fistulated Dallagh sheep were used to determine ruminal BH of unsaturated fatty acids (UFAs). Differences in the disappearance of fatty acids through the bags and lag times were observed between the oilseeds. We saw that the longer the incubation time of the oilseeds in the rumen, the lower the content of C18:2 and C18:3. Significantly higher lag times for both C18:2 and C18:3 were observed in ground canola compared to ground soya bean. BH rates of C18:2 and C18:3 fatty acids in soya bean were three times higher than those of canola. These results suggest that the fatty acid profile of fat source can affect the BH of UFAs by rumen micro‐organisms. So that UFAs of canola had higher ability to escape from ruminal BH. It seems that fatty acid profile of ruminant products is more affected by canola seed compared to soya bean seed.     

Serum biochemical values and mineral element contents of tissues in yaks

Serum biochemical values and the wet weight to dry weight ratios of tissues were determined in yaks in Shandan county of Gansu province. The liver, kidney, heart and muscle contents of seven elements in yaks were also analysed. Most serum biochemical values were similar to those of cattle, camels and sheep, but the calcium concentration was considerably above the normal range for other ruminants. The liver contained the highest concentrations of copper, manganese and cobalt and the kidney of selenium, iron and calcium.Abbreviations Alb albumin - ALT alanine aminotransferase - AST aspartate aminotransferase - BUN blood urea nitrogen - Chol cholesterol - Glob globulin - -GT -glutamyl transpeptidase - IP inorganic phosphorus - TP total protein     

Evaluation of the Microbiological Status of Milk and Various Structures in Mammary Glands from Naturally Infected Dairy Cows

A knowledge of the microbiological status of milk and of the different structures in the mammary glands has great importance in elucidating the pathogenesis of mammary gland infections. The objective of this study was to evaluate the microbiological status of various structures in the mammary glands from naturally infected dairy cows following slaughter. A total of 94 samples of milk, 184 samples of mammary parenchyma, 168 samples of gland cisterns, and 168 samples of teat cisterns were collected for microbiological examination. Microorganisms were detected in 59.9% of all samples, 67.0% of the milk samples, 70.1% of the mammary parenchymas, 55.9% of the gland cisterns and 48.8% of the teat cistern samples. When all samples were considered, coagulase-negative Staphylococcus were the most prevalent (35.7%) followed by coagulase-positive Staphylococcus (12.2%), Corynebacterium bovis (2.4%), Prototheca sp. (1.9%), and Streptococcus dysgalactiae (1.5%). There was a significantly higher occurrence of microorganisms in the milk and mammary parenchyma compared to the gland cisterns and teat cisterns. This revised version was published online in July 2006 with corrections to the Cover Date.     

Development and survival of free-living stages of gastrointestinal nematodes of sheep and goats on pasture in the Nigerian derived savanna

Four grass plots were sequentially contaminated with goat faeces containing known numbers of unembryonated eggs of predominantly Haemonchus contortus and Trichostrongylus spp. between October 1982 and April 1983. Four other plots were similarly contaminated with sheep faeces between February and May 1987. An additional plot was repeatedly contaminated with sheep faeces from February to April 1987. Populations of free-living stages in faeces and of infective larvae (L₃) in the herbage were subsequently monitored until the end of April and June of 1983 and 1987 respectively. During February and May 1987 two control cultures of sheep faeces were incubated in the laboratory at 25°C–30°C and at a constant temperature of 50°C and the free-living development was also monitored. L₃ developed very readily in the faeces cultured at 25°C–30°C and in those spread on a grass plot in October, at the end of the wet season, but developed less on the plot contaminated in May at the start of the wet season. Worm eggs in faeces deposited on plots during the hot dry season (December to April) or incubated at 50°C died and disintegrated after 24–48 h exposure to the high environmental temperatures. The results indicate that it is unlikely that gastrointestinal nematodes of sheep and goats can develop or survive on open pasture during the dry season in the Nigerian derived savanna zone.