系数倍率法检测伊维菌素脂质体含量的研究

伊维菌素脂质体是伊维菌素的一种重要新剂型,为消除辅料对伊维菌素含量测定的影响,采用系数倍率法在245nm和222nm处不经分离直接测定脂质体中伊维菌素的含量。结果表明,伊维菌素在4～28μg／mL范围内呈良好的线性关系,r=0．9999,平均回收率为104．6％。说明系数倍率法能消除脂质体中卵磷脂与胆固醇对伊维菌素含量测定的影响,可作为伊维菌素脂质体质量控制的有效方法。     

伊维菌素小单室脂质体工艺配方优化及质量分析

为获得高包封率的伊维菌素小单室脂质体,本研究对其制备工艺进行了优化,并选取超声波频率、超声时间、卵磷脂与胆固醇质量比、伊维菌素与卵磷脂质量比各因素进行正交交互作用考察,同时利用反相高效液相色谱法对各工艺配方组合下伊维菌素小单室脂质体的包封率进行了测定。结果显示,伊维菌素小单室脂质体的制备最佳配方和工艺组合为超声波频率200 kHz,超声时间6 min,伊维菌素与大豆卵磷脂质量比为1:10。经过优化组合,得到了较高品质的伊维菌素小单室脂质体,平均载药量达到(92.35±0.61)%,药物品质优良,且制备工艺简单可行。     

高效液相色谱法测定伊维菌素脂质体药物的含量及包封率

本试验旨在建立伊维菌素脂质体载体药物含量及包封率测定的高效液相色谱法。Waters surfire C18柱(150 mm×2.1 mm,5 μm),流动相为乙腈—甲醇—水(62∶30∶8),流速1 mL/min,检测波长245 nm,进样量10 μL,柱温30 ℃。采用凝胶过滤法、透析法、冷冻超速离心法、超滤离心法4种方法对脂质体与药物进行分离。结果表明,在优化色谱条件下伊维菌素与辅料及溶剂峰均得到良好分离,伊维菌素在1～50 μg/mL浓度范围内线性关系良好(r=0.9998,n=5),最终采用超速冷冻离心法可将脂质体与药物很好的分离,伊维菌素脂质载体的包封率可达98.54%±1.6%。该方法准确可靠、简单快速,可用于伊维菌素脂质体载体药物含量及包封率的测定。     

伊维菌素聚酯酸酐微球的制备

将2种聚酯酸酐(P(SA∶RA 20∶80),P(SA∶RA 30∶70))分别与伊维菌素溶于三氯甲烷中作为有机相,以聚乙烯醇水溶液为水相,用乳化溶剂挥发法制备出2种伊维菌素聚酯酸酐微球。采用光学显微镜考察所制备微球的形态及粒径,紫外分光光度法测定载药量和包封率。结果显示,制备出的P(SA∶RA 30∶70)/IVM微球的平均粒径为(72.240±24.747)μm,载药量为19.67%,包封率为87.70%。P(SA∶RA 20∶80)/IVM微球的平均粒径为(64.18±26.14)μm,载药量为17.72%,包封率为87.27%。这表明采用乳化溶剂挥发法成功制备出2种伊维菌素聚酯酸酐微球。     

瑞香狼毒脂质体制备及包封率的测定

目的建立瑞香狼毒脂质体包封率的检测方法.方法:采用乙醚注入法制备脂质体,进而紫外分光光度法测出瑞香狼毒脂质体的包封率.结果凝胶柱层析法能有效分离脂质体与瑞香狼毒,柱回收率和柱加样回收率分别为99.09%和98.35%.瑞香狼毒线性范围为0.160～24.048μg·mL-1(r=0.9998),测得包封率平均值为36.12%,RSD为1.18%.结论该方法简便易行,准确可靠,可用于瑞香狼毒脂质体包封率的测定.     

伊维菌素聚酯酸酐微球的制备

将2种聚酯酸酐（P（SA：RA20：80）,P（SA：RA30：70））分别与伊维菌素溶于三氯甲烷中作为有机相,以聚乙烯醇水溶液为水相,用乳化溶剂挥发法制备出2种伊维菌素聚酯酸酐微球。采用光学显微镜考察所制备微球的形态及粒径,紫外分光光度法测定载药量和包封率。结果显示,制备出的P（SA：RA30：70）／IVM微球的平均粒径为（72．240±24．747）μm,载药量为19．67％,包封率为87．70％。P（SA：RA20：80）/IVM微球的平均粒径为（64．18±26．14）μm,载药量为17．72％,包封率为87．27％。这表明采用乳化溶剂挥发法成功制备出2种伊维菌紊聚酯酸酐微球。     

流感疫苗脂质体制备的初步研究

以包封率为依据,采用薄膜分散法制备疫苗脂质体,以Lowry检测法测定包封率.结果制备得到包封率高于84%的疫苗脂质体.制备过程中冻融处理、磷脂用量对疫苗脂质体包封率影响较大,该实验筛选得到的配方能制备得到较高包封率的疫苗脂质体.     

伊维菌素微胶囊的制备及其体外释放的研究

市售伊维菌素制剂存在生物利用度低,释药峰谷浓度差异大等问题,本文以明胶为囊材,采用单凝聚法制备伊维菌素长效注射微胶囊油混悬剂。以微胶囊的粒径、载药量和包封率为制备工艺的优化指标,采用分光光度法测定微胶囊内药物含量及包封率。结果显示：最佳工艺制备的微胶囊的平均包封率为63.2%,载药量为18.3%,微胶囊的正圆度高、表面平滑,粒径分布在20~50 μm,药物呈缓慢持续释放,体外累计释放率18 h为30.0%,44 h后仅为51.0%。伊维菌素微胶囊制剂可大大增加体内留存时间,提高生物利用度,缓释效果显著。     

伊维菌素微胶囊的制备及其性质研究

对伊维菌素微胶囊进行制备、表征及其性质研究。以辛烯基琥珀酸酯化淀粉为壁材,伊维菌素为芯材,按照一定比例混合后,进行超声乳化,冷冻干燥14h得到微胶囊。红外光谱法对微胶囊产品进行表征,高效液相色谱法对伊维菌素含量进行测定,同时研究了光照和温度对其稳定性的影响。结果表明：用冷冻干燥法制备的微胶囊的包封率可达到92．27％;连续光照5h和在30～60℃下保存24h,微胶囊性质稳定;红外图谱显示微胶囊制备成功。冷冻干燥法制备伊维菌素微胶囊包埋效果良好,且该微胶囊的光热稳定性良好。     

阿莫西林脂质体的制备及质量评价

采用薄膜分散法制备阿莫西林脂质体,以粒径和包封率为指标评价其质量.前期以正交设计优化筛选出最佳制备工艺,以最优工艺制备阿莫西林脂质体,测定其平均粒径和包封率.实验所制得的脂质体的平均粒径为114.6 nm,包封率为64.89％.结果表明,采用薄膜分散法制备阿莫西林脂质体的方法可行,阿莫西林脂质体的制备为兽药新剂型的研究与应用提供了有价值的参考.     

Anthelmintic efficacy of ivermectin in naturally parasitized cats

Ivermectin was administered per os [( PO]; n = 15) or subcutaneously [( SC]; n = 3) to naturally parasitized cats at 10 (n = 6), 100 (n = 6), or 300 (n = 6) micrograms/kg of body weight. Nontreated control cats were given sterile isotonic saline solution PO (n = 5) or SC (n = 1). Qualitative fecal examinations were performed on each cat 1 day before treatment and 14 days after treatment. Cats were euthanatized 14 days after treatment, at which time parasites from the gastrointestinal tracts were recovered, identified, and enumerated. Lungs and urinary bladders were examined histologically or by digestion (lungs only) for Capillaria spp and/or Aelurostrongylus abstrusus. Ivermectin was effective in removing Ancylostoma spp at all doses, but removal of Toxocara cati required 300 micrograms of ivermectin/kg. Efficacies against A abstrusus, Capillaria spp, and Physaloptera spp could not be determined definitively. Ivermectin had no effect on Dipylidium caninum, Hydatigera taeniaeformis, Spirometra mansonoides, or Isospora spp. Adverse reactions were not observed in cats given ivermectin PO; however, 3 cats given ivermectin SC reacted as though they experienced pain at the injection site.     

Comparison of the anthelmintic efficacy of oxfendazole or ivermectin administered orally and ivermectin administered subcutaneously to sheep during the periparturient period

The suppression of nematode egg output in faeces was measured in ewes treated just before lambing with either oxfendazole or ivermectin by oral drench or with ivermectin by subcutaneous injection. Ivermectin and oxfendazole given orally were similarly effective, whereas ivermectin given by subcutaneous injection extended the period of suppressed egg output by about one week. The more persistent anthelmintic effect of ivermectin given subcutaneously was probably due to its extended half-life in the plasma of treated sheep. Plasma pepsinogen activity was less in the sheep given anthelmintic than in the untreated controls. Ivermectin caused a significantly greater reduction in pepsinogen activity than oxfendazole and was more effective when given subcutaneously than when given orally.     

Ivermectin for the control of swine scabies: relative values of prefarrowing treatment of sows and weaning treatment of pigs

Ivermectin given in a single subcutaneous dose (300 micrograms/kg of body weight) was tested for activity against swine scabies (Sarcoptes scabiei). Efficacy was determined by recoveries of mites from ear scrapings and by observations of clinical signs. Treatment of infected sows 8 to 37 days before farrowing eliminated scabies from the sows and prevented its transmission to their offspring. Pigs farrowed by ivermectin-treated sows remained noninfected throughout the study regardless of whether they were treated with ivermectin at weaning. Placebo-treated sows remained infected and transmitted scabies to their offspring. Ivermectin treatment of pigs at weaning eliminated the infection, whereas placebo treatment did not. The placebo-treated pigs remained infected while in the nursery, but ivermectin treatment eliminated the infection when they were moved to the growing and finishing floor at 12 weeks of age. It appears that an effective control program for swine scabies using ivermectin could be based on a single treatment of the sows before farrowing. Any infection (epizootic) appearing in growing pigs could be controlled by a single treatment of all in-contact pigs.     

Persistence of ivermectin in plasma and faeces following administration of a sustained-release bolus to cattle

Six calves (weight 210 to 230 kg) were dosed with an intra-ruminal slow-release bolus prepared to deliver ivermectin at a low daily dosage for 135 days. Ivermectin concentrations in jugular blood 160 days post-treatment were determined by high performance liquid chromatography (HPLC) using fluorescence detection. Ivermectin plasma concentrations increased gradually to achieve the steady-state concentration (20 ng ml(-1)) at approximately four days post-treatment, which was maintained for 120 days. The ivermectin peak plasma concentration (28.5 ng ml(-1)) was attained at 15 days post-administration of the bolus. The faecal ivermectin concentration rose to a maximal concentration of 4.1 microg g(-1) at four days post-treatment, dropping to a steady-state concentration of around 1.18 microg g(-1) which was maintained up to 120 days post-treatment. Ivermectin was detected in both plasma (0.05 ng ml(-1)) and faeces (2.67 ng g(-1)) up to 160 days. The high levels of ivermectin recovered in faeces indicate that a large proportion of the dose released by the bolus (80 to 90 per cent) is excreted in faeces.     

不同驱虫药物对奶山羊消化道线虫驱虫效果研究

本研究旨在观察不同驱虫药物对奶山羊消化道线虫的驱虫效果,为今后寄生虫病的防治筛选更好的驱虫药物。选取奶山羊96只,分3组,每组32只,分别投喂伊维菌素注射液、芬苯达唑粉和伊维菌素芬苯达唑预混剂3种驱虫药物,采用饱和盐水漂浮法和麦克马斯特法检测驱虫前后线虫的感染情况。结果发现:伊维菌素注射液组虫卵转阴率为6.25%;芬苯达唑粉剂组虫卵转阴率为31.25%;伊维菌素芬苯达唑预混剂组虫卵转阴率为50.00%。驱虫前后感染强度伊维菌素注射液组差异显著(P<0.05),芬苯达唑粉剂组差异极显著(P<0.01),伊维菌素芬苯达唑预混剂组差异极显著(P<0.01)。因此,建议采用伊维菌素芬苯达唑预混剂作为奶山羊消化道线虫首选驱虫药物。     

伊维菌素在不同动物中安全性、药效学和药代动力学的差异性研究进展

伊维菌素是一种被广泛应用于多种畜禽线虫病和外寄生虫病防控的抗寄生虫药物。由于伊维菌素具有非常突出的优点,在不同种属动物上使用时,其安全性、药效学和药代动力学的差异更容易被人们忽略。忽略动物种属差异,可能会导致寄生虫病防治失败,甚至安全事故的发生。对伊维菌素在不同动物中的安全性、药效学和药代动力学差异做一综述,以期为伊维菌素的临床用药提供参考,保障伊维菌素在不同动物中用药的安全性和有效性。     

Ivermectin effects on motor coordination and contractions of isolated rat diaphragm

Ivermectin, the antiparasitic drug from the macrocyclic lactones class raises attention due to its high efficiency against nematodes and arthropods and very specific toxic and side effects that it may produce in host. Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality. In our study increasing intravenous doses of ivermectin, (6 or more times higher than therapeutic dose: 1.25, 2.5, 3.75, 5.0, 6.25 and 7.5 mg/kg), caused dose-dependent disturbance of motor coordination in treated rats. The median effective dose (ED50) that was able to impair the rota-rod performance in rats treated 3 min before testing was 2.52 mg/kg. This effect weakens over time, while in the rats treated 60 min before the rota-rod test, ED50 of ivermectin was 4.21 mg/kg. Whereas, all tested doses of ivermectin did not cause any other clinical symptoms of toxicity. Ivermectin has no effect on the contractions of isolated diaphragm caused by the EFS, which effectively blocked mecamylamine (100 μM) and pancuronium (1 and 2 μM). Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects.     

Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat

The tissue concentration and efficacy of ivermectin after per os and subcutaneous administration were compared in goats experimentally infected with Trichostrongylus colubriformis (ivermectin-susceptible strain, INRA). Infected goats (n = 24) were treated per os (n = 9) or subcutaneously (n = 9) with ivermectin, 0.2 mg/kg, or kept as not treated controls. The faecal egg counts and small intestine worm counts were determined. Ivermectin concentration was measured in the plasma, gastrointestinal tract, lung, skin or hair, liver and adipose tissues at 0, 2, 7 and 17 days post-treatment. The efficacy of ivermectin against T. colubriformis infection in goat was 98.7 and 99.9% for subcutaneous and oral administration, respectively. Ivermectin concentration declined with time and only residual concentration was measured at 17 days post-treatment in plasma and gastrointestinal tract. Ivermectin concentration was higher after subcutaneous compared to per os injection in most of the tissue examined. In skin, hair and subcutaneous adipose tissue ivermectin persisted at significant concentrations 17 days post-treatment for both routes of administration. In our experimental conditions, ivermectin provides similar efficacy against T. colubriformis after subcutaneous or per os administration in goat. However, the lower ivermectin levels in tissues after per os administration suggest that the lasting of efficacy may be shortened after per os compared to subcutaneous administration especially in animals with poor body condition in pasture where re-infection occurs quickly after anthelmintic treatment.     

Prophylaxis of nematode infections in cattle with an indwelling rumino-reticular ivermectin sustained release bolus

Ivermectin delivered continuously from a rumino-reticular sustained release device was prophylactically effective in preventing establishment of nine nematode parasite species in multiply-exposed cattle. Ivermectin dosages which permitted less than or equal to 1% of infected control calf worm populations to establish ranged from less than 2.5 micrograms kg-1 day-1, which totally prevented infection with Dictyocaulus viviparus and Oesophagostomum radiatum, to approximately equal to 30 micrograms kg-1 day-1 required to suppress Nematodirus helvetianus to the same extent. Between these extremes, in decreasing order of sensitivity to enterical sustained release ivermectin, were Ostertagia ostertagi, Trichostrongylus axei, Haemonchus placei, Cooperia punctata, C. oncophora and T. colubriformis which were maximally affected at less than or equal to 10 micrograms kg-1 day-1 of ivermectin.     

The Effect of Ivermectin on Convulsions in Rats Produced by Lidocaine and Strychnine

Ivermectin is one of the most commonly used drugs in pharmacotherapy of parasitic diseases in domestic and wild animals caused by parasitic nematodes and arthropods. However, ivermectin and other avermectins very often produce side-effects in hosts. The most dominant clinical symptom of ivermectin toxicity in domestic and wild animals is CNS depression. In nematodes, the target site of ivermectin’s action is glutamate-gated chloride-channel receptor and GABA receptor. The depressive effect of ivermectin in mammals might include more than one mechanism; therefore, the anticonvulsive effect of ivermectin against convulsions caused by lidocaine and strychnine was evaluated. Ivermectin antagonized lidocaine- and strychnine-induced convulsions in rats, although these have different mechanisms. In the present study, the anticonvulsive ED₅₀ of ivermectin for lidocaine-induced convulsions was 2.44 mg/kg (95% CL 1.67 to 3.57 mg/kg), whereas for convulsions induced by strychnine it was higher at 4.25 mg/kg (95% CL 2.32 to 3.78 mg/kg). At the same time, both anticonvulsive doses are significantly lower then the observed LD₅₀ of ivermectin (18.20 mg/kg). Furthermore, flumazenil (0.1 and 0.2 mg/kg), an antagonist of benzodiazepine receptors, antagonizes just one part of these anticonvulsive effects of ivermectin. Our results show the significant anticonvulsive properties of ivermectin and support the findings that ivermectin in the CNS of mammals produces multiple inhibitory effects, probably through participation in the function of GABA-sensitive and GABA-insensitive chloride channels.