伊维菌素—二氧化硅纳米缓释颗粒的制备及抗球虫新制剂抗鸡球虫效力试验

发布时间：2018-04-24 17:13

本文选题：伊维菌素 + 纳米二氧化硅　；参考：《河南农业大学》2015年硕士论文

【摘要】：伊维菌素作为抗寄生虫药物有许多非常突出的特点,例如杀虫活性高,抗虫谱广,对大多数体内外寄生虫均有良好的治疗作用;能够应用于多种动物;可通过多种途径给药,包括口服、皮下注射以及肌肉注射等方式;使用安全,推荐剂量使用不会出现中毒作用,而且没有致畸和致癌作用。空心纳米SiO_2是一种多孔无机纳米材料,特点是比表面积大、生物相容性良好、抗高机械强度和高热,同时由于表面极易引进其他很多功能团的生物分子,因而在生物学方面已被用于作为催化剂载体、用于酶的固定化和生物标记等方面,尤其是被用来研究药物缓释控释、靶向、智能给药等方面。本试验将不溶于水的伊维菌素溶解到无水乙醇中,以纳米二氧化硅为载体,V乙醇:V硅溶胶的体积比分别为2.5:1和3:1的条件下制备出理论载药量分别为1%、2%和5%的三种含量伊维菌素-二氧化硅纳米载药颗粒,分别采用热重分析法和紫外分光光度计法检测三种药物的实际载药量,并通过体外缓释试验考察药物的吸附和缓释情况。结果如下:在V乙醇:V硅溶胶的体积比为2.5:1的比例下,热重分析法检测得到理论载药量为1%、2%和5%的实际载药量0.59%、1.51%和3.07%;在V乙醇:V硅溶胶的体积比为3:1的比例下,热重分析法检测得到理论载药量为1%、2%和5%的实际载药量为0.24%、1.09%和2.36%。在245nm条件下建立标准曲线方程y=34471.87631x+0.00162(R2=0.99991),使用制备伊维菌素-二氧化硅纳米缓释颗粒时保存的上清液检测得到缓释颗粒的实际载药量和包封率,在V乙醇:V硅溶胶的体积比为2.5:1的比例下,理论载药量为1%、2%和5%的实际载药量为0.63%、1.58%和3.25%,包封率分别为78.24%、96.85%和75.07%;在V乙醇:V硅溶胶的体积比为3:1的比例下,检测得到理论载药量为1%、2%和5%的实际载药量为0.24%、1.05%和2.03%,包封率分别为25.59%、55.93%和5.94%。热重分析和紫外检测结果表明V乙醇:V硅溶胶的体积比为2.5:1时的载药量和包封率均高于其体积比为3:1时。体外缓释结果表明伊维菌素原药114h达到溶解平衡,而缓释颗粒则有良好的缓释行为,理论载药量为1%、2%的缓释颗粒在150h左右达到溶解平衡,理论载药量为5%的缓释颗粒在150h的累积缓释率才达到50%左右。累积缓释率随着载药量的增大而逐渐增大,但均小于原药的释放率。说明本试验制备的伊维菌素-二氧化硅纳米缓释颗粒的可控释放是可行的,且制备简单,成本低廉,是一种有望用于临床的新制剂。鸡球虫病是由柔嫩艾美耳球虫引起的一种肠道寄生虫病,在临床上通常以发病率和死亡率高为特征,给鸡养殖业造成了巨大的经济损失。该病对15-50日龄雏鸡危害尤为严重,死亡率能达到80%以上。经治疗后病鸡即使被治愈,但是其生长发育受阻,长时间得不到恢复。地克珠利是一种具有高效、广谱、低毒的抗球虫药,但是其不溶于水,给临床用药带来不便。为测定某生物科技有限公司研制的0.5%水溶性地克珠利预混剂的抗球虫效力,应用15日龄AA+肉鸡,每只经嗉囊1次接种1×105个抗地克珠利的柔嫩艾美耳球虫(Eimeria tenella)孢子化卵囊,按每千克饲料添加0.5mg、1mg、2mg水溶性地克珠利混饲,设1mg、2mg市售地克珠利和125mg尼卡巴嗪预混剂为对照,结果6个组的ACI分别为67、96、95.74、110.53、95.61、113.97,均在160以下,表明所用三种药物对该虫株的药效均较差;新方法制备的地克珠利通过提高吸收度并不能提高该药的抗球虫效果,且增加用药量仍不能提高该药的抗球虫效果;试验用虫株对尼卡巴嗪亦存在耐药性。
[Abstract]:Ivermectin, as an anti parasite drug, has many very prominent features, such as high insecticidal activity, broad spectrum of insect resistance, good therapeutic effect for most of the parasites in the body and in vivo; it can be applied to a variety of animals; it can be administered in a variety of ways, including oral, subcutaneous, and intramuscular injection; safety and recommended doses are used. There is no toxic effect and no teratogenicity and carcinogenesis. Hollow nano SiO_2 is a porous inorganic nanomaterial characterized by large surface area, good biocompatibility, high resistance to high mechanical strength and high heat. At the same time, because the surface is very easy to introduce many other functional groups, it has been used as a biological agent in biology. Catalyst carrier, used for immobilization of enzymes and biomarkers, especially for the study of drug release, targeting, and intelligent drug delivery. The insoluble ivermectin was dissolved into anhydrous ethanol, nano silica was used as the carrier, and the volume ratio of V ethanol: V silica sol was prepared under the conditions of 2.5:1 and 3:1, respectively. 1%, 2% and 5% contents of ivermectin silica nanoparticles were obtained, respectively. The actual drug loading of three drugs was detected by thermogravimetric analysis and ultraviolet spectrophotometer respectively. The adsorption and release conditions of the drugs were investigated by the sustained release test in vitro. The results were as follows: the volume ratio of the V ethanol: V silica sol Under the proportion of 2.5:1, the theoretical drug loading of 1%, 2% and 5% was measured by thermogravimetric analysis (0.59%, 1.51% and 3.07%). Under the ratio of the volume ratio of V silica sol to 3:1, the theoretical drug loading was 1%, 2% and 5%, and 0.24%, 1.09% and 2.36%. were established under the 245nm condition to establish a standard curve. Equation y=34471.87631x+0.00162 (R2=0.99991), the actual drug loading and encapsulation efficiency of the sustained-release granules were obtained by using the supernatant preserved in the preparation of ivermectin silica nanoparticles. In the proportion of the volume ratio of V ethanol: V silica sol to 2.5:1, the theoretical drug loading of 1%, 2% and 5% was 0.63%, 1.58% and 3.25%. The encapsulation rates were 78.24%, 96.85% and 75.07%, respectively, when the volume ratio of V ethanol: V silica sol was 3:1, the actual drug loading of 1%, 2% and 5% was 0.24%, 1.05% and 2.03%, and the encapsulation efficiency was 25.59%, 55.93% and 5.94%. thermogravimetric analysis and UV detection results showed that the volume ratio of V ethanol: V silica sol was 2.5:1. The drug volume and encapsulation efficiency were higher than the volume ratio of 3:1. The in vitro release results showed that the ivermectin 114h reached the dissolution balance, while the sustained release particles had a good release behavior, the theoretical drug loading was 1%, the 2% sustained-release granules reached the dissolution balance around 150h, and the cumulative release rate of the sustained release particles with the theoretical charge of 5% was only 50% in the cumulative release rate. The cumulative release rate increases with the increase of drug loading, but it is less than the release rate of the original drug. It shows that the controlled release of ivermectin silica nanoscale nanoparticles prepared by this experiment is feasible and is simple and inexpensive. It is a promising new preparation for clinical use. Coccidiosis of chicken is induced by Eimeria tenella A kind of intestinal parasitic disease, usually characterized by high incidence and high mortality in clinic, has caused huge economic loss to the chicken breeding industry. The disease is particularly serious to 15-50 day old chicks, and the mortality rate can reach more than 80%. After treatment, the disease chicken is cured, but its growth and development are blocked for a long time and can not be recovered for a long time. Pearl is an anti coccidiosis drug with high efficiency, broad-spectrum and low toxicity, but it is insoluble in water and inconveniences the clinical use of drugs. In order to measure the anti coccidian effect of 0.5% water-soluble diurli premixture developed by a biotech limited company, 15 day old AA+ broilers were used to inoculate 1 * 105 tender eimeri balls of 1 x 105 anti dixulli by the crop. Eimeria tenella sporulation oocyst was fed with 0.5mg, 1mg, 2mg water soluble kzulli, 1mg, 1mg, 2mg city and 125mg Ni CBA premixture, the results of the 6 groups were 67,96,95.74110.53,95.61113.97, respectively, both below 160, indicating that the efficacy of the three drugs was poor. The new method can not improve the anti coccidiosis effect of the drug by increasing the absorbance, and the increase of the dosage still can not improve the anti coccidian effect of the drug; the test insect strain also has resistance to nicardizine.

【学位授予单位】：河南农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S859.795

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