本文選題：伊維菌素 + 納米二氧化硅　； 參考：《河南農(nóng)業(yè)大學(xué)》2015年碩士論文

【摘要】：伊維菌素作為抗寄生蟲藥物有許多非常突出的特點(diǎn),例如殺蟲活性高,抗蟲譜廣,對(duì)大多數(shù)體內(nèi)外寄生蟲均有良好的治療作用;能夠應(yīng)用于多種動(dòng)物;可通過多種途徑給藥,包括口服、皮下注射以及肌肉注射等方式;使用安全,推薦劑量使用不會(huì)出現(xiàn)中毒作用,而且沒有致畸和致癌作用�？招募{米SiO_2是一種多孔無機(jī)納米材料,特點(diǎn)是比表面積大、生物相容性良好、抗高機(jī)械強(qiáng)度和高熱,同時(shí)由于表面極易引進(jìn)其他很多功能團(tuán)的生物分子,因而在生物學(xué)方面已被用于作為催化劑載體、用于酶的固定化和生物標(biāo)記等方面,尤其是被用來研究藥物緩釋控釋、靶向、智能給藥等方面。本試驗(yàn)將不溶于水的伊維菌素溶解到無水乙醇中,以納米二氧化硅為載體,V乙醇:V硅溶膠的體積比分別為2.5:1和3:1的條件下制備出理論載藥量分別為1%、2%和5%的三種含量伊維菌素-二氧化硅納米載藥顆粒,分別采用熱重分析法和紫外分光光度計(jì)法檢測(cè)三種藥物的實(shí)際載藥量,并通過體外緩釋試驗(yàn)考察藥物的吸附和緩釋情況。結(jié)果如下:在V乙醇:V硅溶膠的體積比為2.5:1的比例下,熱重分析法檢測(cè)得到理論載藥量為1%、2%和5%的實(shí)際載藥量0.59%、1.51%和3.07%;在V乙醇:V硅溶膠的體積比為3:1的比例下,熱重分析法檢測(cè)得到理論載藥量為1%、2%和5%的實(shí)際載藥量為0.24%、1.09%和2.36%。在245nm條件下建立標(biāo)準(zhǔn)曲線方程y=34471.87631x+0.00162(R2=0.99991),使用制備伊維菌素-二氧化硅納米緩釋顆粒時(shí)保存的上清液檢測(cè)得到緩釋顆粒的實(shí)際載藥量和包封率,在V乙醇:V硅溶膠的體積比為2.5:1的比例下,理論載藥量為1%、2%和5%的實(shí)際載藥量為0.63%、1.58%和3.25%,包封率分別為78.24%、96.85%和75.07%;在V乙醇:V硅溶膠的體積比為3:1的比例下,檢測(cè)得到理論載藥量為1%、2%和5%的實(shí)際載藥量為0.24%、1.05%和2.03%,包封率分別為25.59%、55.93%和5.94%。熱重分析和紫外檢測(cè)結(jié)果表明V乙醇:V硅溶膠的體積比為2.5:1時(shí)的載藥量和包封率均高于其體積比為3:1時(shí)。體外緩釋結(jié)果表明伊維菌素原藥114h達(dá)到溶解平衡,而緩釋顆粒則有良好的緩釋行為,理論載藥量為1%、2%的緩釋顆粒在150h左右達(dá)到溶解平衡,理論載藥量為5%的緩釋顆粒在150h的累積緩釋率才達(dá)到50%左右。累積緩釋率隨著載藥量的增大而逐漸增大,但均小于原藥的釋放率。說明本試驗(yàn)制備的伊維菌素-二氧化硅納米緩釋顆粒的可控釋放是可行的,且制備簡(jiǎn)單,成本低廉,是一種有望用于臨床的新制劑。雞球蟲病是由柔嫩艾美耳球蟲引起的一種腸道寄生蟲病,在臨床上通常以發(fā)病率和死亡率高為特征,給雞養(yǎng)殖業(yè)造成了巨大的經(jīng)濟(jì)損失。該病對(duì)15-50日齡雛雞危害尤為嚴(yán)重,死亡率能達(dá)到80%以上。經(jīng)治療后病雞即使被治愈,但是其生長(zhǎng)發(fā)育受阻,長(zhǎng)時(shí)間得不到恢復(fù)。地克珠利是一種具有高效、廣譜、低毒的抗球蟲藥,但是其不溶于水,給臨床用藥帶來不便。為測(cè)定某生物科技有限公司研制的0.5%水溶性地克珠利預(yù)混劑的抗球蟲效力,應(yīng)用15日齡AA+肉雞,每只經(jīng)嗉囊1次接種1×105個(gè)抗地克珠利的柔嫩艾美耳球蟲(Eimeria tenella)孢子化卵囊,按每千克飼料添加0.5mg、1mg、2mg水溶性地克珠利混飼,設(shè)1mg、2mg市售地克珠利和125mg尼卡巴嗪預(yù)混劑為對(duì)照,結(jié)果6個(gè)組的ACI分別為67、96、95.74、110.53、95.61、113.97,均在160以下,表明所用三種藥物對(duì)該蟲株的藥效均較差;新方法制備的地克珠利通過提高吸收度并不能提高該藥的抗球蟲效果,且增加用藥量仍不能提高該藥的抗球蟲效果;試驗(yàn)用蟲株對(duì)尼卡巴嗪亦存在耐藥性。
[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.

【學(xué)位授予單位】：河南農(nóng)業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：S859.795

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