氟苯尼考肠溶缓释包衣微粒的制备及体外评价

采用湿法制粒、流化床包衣制备肠溶缓释微粒,正交法进行微粒处方、工艺参数的筛选,通过溶出度试验对其释放特性进行考察,筛选最佳工艺处方。在此优选处方和工艺条件下制得的微粒体外释放特性良好,在人工胃液中几乎不溶,而在人工肠液中释放达80％以上。本品处方合理,制备工艺简单,达到了肠溶缓释的目的,为氟苯尼考制剂的优化提供了依据。     

替米考星肠溶微丸的制备及其评价

采用挤出滚圆法制备含药微丸,药物以固体分散体的形式存在微丸中,流化床进行肠溶包衣,制得替米考星肠溶微丸。通过不同的工艺处方筛选,考察其理化性质及体外释放特性。分别采用紫外分光光度计测定替米考星的含量,电子显微镜、红外分光光度法和差示扫描量热法确证微丸的特性。结果显示,微晶纤维素在一定程度上对微丸骨架的成型有影响,而包衣的厚度影响微丸的体外释放行为。释放度实验表明替米考星肠溶微丸能达到肠溶制剂的效果。     

小檗碱肠溶微囊的研制

为提高小檗碱生物利用度,并改善其对动物的适口性,采用醇提法从黄连中提取出小檗碱成分,以液中干燥法制备小檗碱成分肠溶微囊,并通过单因素试验对影响微囊形成的几个关键条件进行筛选。结果显示,小檗碱成分肠溶微囊制备的最佳工艺条件为：小檗碱∶羟丙基甲基纤维素邻苯二甲酸酯（HPMCP）=1∶7,HPMCP∶丙酮乙醇混合液=1∶20,丙酮乙醇混合液∶液体石蜡=1∶5,司班80∶液体石蜡=6∶100。以此工艺制备3批微囊,其平均包封率为93.32%,微囊外观规整,呈现均匀的流动性和分散性,粒径大小在5～55μm,平均粒径为30.54μm;微囊在人工胃液中2h内溶出少于2%,而在人工肠液中2h释放达到97.343%,几乎达到完全释放,符合中华人民共和国药典的要求。     

替米考星肠溶微丸的质量评价

采用高效液相色谱法和体外溶出度试验测定替米考星肠溶微丸的载药量和溶出度,对自行研制的替米考星肠溶微丸进行初步质量评价。结果显示,制剂含量平均在20%,在人工胃液中不溶出,在人工肠液中溶出度达90%以上,达到了肠溶效果。     

布拉酵母菌活菌制剂制备方法的比较研究

通过对布拉酵母菌生长特性的试验,确定了制备布拉酵母菌活菌制剂的最佳生长条件,并进行了活菌制剂的制备,与喷雾干燥法相比,确定了冷冻干燥法为最佳工艺。在此工艺基础上,做了3批次冻干试验,菌种存活率达到85%以上,室温及37℃贮存3个月存活率分别为78%、54%,其肠衣微囊在模拟肠环境中50min达到完全释放。     

熔融法制备包被纳米氧化锌工艺方法的研究

以纳米氧化锌与二氧化硅作为芯材,硬脂酸作为包被壁材,采用熔融分散-冷却法制备包被纳米氧化锌,以包被纳米氧化锌在人工胃液中的溶出率作为评价指标,得到最佳工艺条件:氧化锌、二氧化硅、硬脂酸的物料配比为50.3.3。在此工艺条件下,纳米氧化锌在人工胃液中3 h后的溶出率为1.87%,在人工肠液中6 h后的释放率为92.35%。该产品能够在仔猪的胃环境中保护纳米氧化锌,并且在仔猪的肠道环境中将纳米氧化锌释放出去,达到使纳米氧化锌发挥最大作用的目的。     

复方肉桂醛微囊的制备及质量评价

试验旨在优化复方肉桂醛微囊的制备工艺，评价复方肉桂醛微囊的质量。试验以乙基纤维素为壁材，采用单凝聚法制备复方肉桂醛微囊，单因素试验探讨芯壁比、加水量、搅拌速度对微囊形成的影响，以包埋率与微囊产率为评价指标，通过正交试验，筛选最优工艺参数，并对正交试验结果进行验证。结果显示，最优工艺为芯壁比4∶5、加水量为每克乙基纤维素使用25 mL的蒸馏水、搅拌速度800 r/min，获得最佳包埋率为30.73%，对应产率为69.03%。微观形态观察结果显示有新构象形成，表明微囊制备成功。溶出度试验结果表明，在溶液中药物未达到一定质量浓度时，微囊会快速释放；当溶液中药物达到一定质量浓度时，药物释放速率将会减慢并逐渐趋于稳定。研究表明，试验通过复方肉桂醛的特殊微囊包被处理技术，筛选出了复方肉桂醛微囊的最优制备工艺，为植物精油产品进一步研究提供参考。     

肠溶淀粉酶的开发与评估

本研究旨在开发一种肠溶性淀粉酶并评估其效果。利用流化床技术对普通淀粉酶进行包被以制备肠溶淀粉酶。采用体外三步法评估肠溶淀粉酶的释放曲线:将肠溶淀粉酶分别在pH 7.0、3.0和7.0的缓冲液中培养5 min、1 h和2 h,模拟单胃动物的口腔/食道、胃和小肠环境。结果表明所制备的肠溶淀粉酶在口腔/食道和胃环境中高度稳定,进入小肠后能得到完全的释放。利用成年公鸡的代谢试验研究了肠溶淀粉酶与普通淀粉酶比例对表观代谢能(AME)的影响。结果发现:总酶活不变,当肠溶淀粉酶与普通淀粉酶按75:25进行饲喂时,AME的提高幅度最大(P<0.05)。本研究表明,通过对淀粉酶的肠溶化处理,并与普通淀粉酶进行合理的配比后,在口腔/食道和小肠中均能提高淀粉酶的消化率,效果优于单独使用肠溶淀粉酶或普通淀粉酶。     

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。     

多西环素肠溶微丸的释放度测定

采用紫外分光光度法测定多西环素肠溶微丸的释放度。制剂在酸性介质中释药量符合中国药典对肠溶制剂的要求,在缓冲液介质中快速释药满足多西环素主要在小肠上段吸收的生理特性。     

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.