本文選題：AC4 + 雞�。� 參考：《中國(guó)農(nóng)業(yè)科學(xué)院》2015年碩士論文

【摘要】：雞球蟲病是一種常見的原蟲寄生蟲病,以柔嫩艾美爾球蟲和毒害艾美耳球蟲危害最大,臨床上會(huì)造成雞體重下降、抵抗力下降、高死亡率,每年給養(yǎng)禽業(yè)帶來(lái)巨大損失。AC4是中國(guó)農(nóng)業(yè)科學(xué)院上海獸研究醫(yī)所在地克珠利的結(jié)構(gòu)基礎(chǔ)上合成并篩選出的一種新型三嗪類抗球蟲化合物,臨床前研究表明其抗球蟲效果優(yōu)異,具有廣譜、低毒的特點(diǎn)。本研究的目的是建立檢測(cè)雞和SD大鼠血漿內(nèi)AC4的分析方法,考察高、中、低三個(gè)劑量的AC4在這兩種動(dòng)物的藥代動(dòng)力學(xué)和1.33mg/kg bw劑量下AC4在雞體內(nèi)的口服生物利用度,獲得主要的藥代動(dòng)力學(xué)參數(shù)。在檢測(cè)SD大鼠血漿內(nèi)AC4含量的UPLC-UV方法中:使用乙酸乙酯作為提取溶劑,妥曲珠利亞砜作為內(nèi)標(biāo),BEH C18色譜柱,采用梯度洗脫方式,每個(gè)樣品進(jìn)樣時(shí)間為20 min;方法專屬性良好,檢測(cè)限和定量限分別為0.04、0.08μg/m L;標(biāo)準(zhǔn)曲線定量范圍0.08-80μg/m L,線性方程y=0.091x+0.001,R2=1,線性關(guān)系良好;加標(biāo)樣品提取回收率在97.56-106.2%之間,日內(nèi)、日間精密度均小于6.36%;樣品至少在室溫放置8 h或者反復(fù)凍融三次后穩(wěn)定;該方法靈敏、準(zhǔn)確,可以用于檢測(cè)SD大鼠血漿內(nèi)AC4含量。AC4在SD大鼠體內(nèi)的藥動(dòng)學(xué)實(shí)驗(yàn)中,本文考察了1、2、10 mg/kg bw三個(gè)給藥劑量分別在雌雄SD大鼠的藥代動(dòng)力學(xué),結(jié)果表明:藥時(shí)曲線下面積和最大血藥濃度存在劑量依賴關(guān)系;給藥后4-5 h達(dá)到最大血藥濃度;生物消除半衰期在不同性別、不同劑量組之間存在較大差異;AC4在SD大鼠的藥動(dòng)學(xué)存在較為明顯的性別和個(gè)體差異。在檢測(cè)雞血漿內(nèi)AC4含量的UPLC-UV方法中:使用乙酸乙酯作為提取溶劑,妥曲珠利亞砜作為內(nèi)標(biāo),BEH C18色譜柱,采用梯度洗脫方式,每個(gè)樣品進(jìn)樣時(shí)間為10 min;方法專屬性良好,檢測(cè)限和定量限分別為0.02、0.04μg/m L;標(biāo)準(zhǔn)曲線定量范圍0.04-50μg/m L,線性方程y=0.094x+0.002,R2=0.999,線性關(guān)系良好;加標(biāo)樣品提取回收率在92.97-109.5%之間,日內(nèi)、日間精密度均小于7.84%;樣品至少在室溫放置8h或者反復(fù)凍融三次后穩(wěn)定;該方法靈敏、準(zhǔn)確,可以用于檢測(cè)雞血漿內(nèi)AC4含量。AC4在雞的藥動(dòng)學(xué)實(shí)驗(yàn)中,本文考察了0.45、0.9、4.5 mg/kg bw三個(gè)給藥劑量,結(jié)果表明:藥時(shí)曲線下面積和最大血藥濃度存在劑量依賴關(guān)系;給藥后平均4 h達(dá)到最大血藥濃度;生物消除半衰期與給藥劑量間無(wú)明顯關(guān)系,平均消除半衰期為18.5 h,屬于慢消除類藥物。在AC4的生物利用度實(shí)驗(yàn)中,在給藥劑量為1.33 mg/kg bw下:口服組AUC(0-t)為53.836mg/l*h,靜注組AUC(0-t)為68.068 mg/l*h,由絕對(duì)生物利用度計(jì)算公式F=AUCpo/AUCiv×100%,得到AC4的口服生物利用度為79.1%。綜上所述,本研究分別建立了檢測(cè)雞和SD大鼠血漿內(nèi)AC4含量的UPLC-UV方法學(xué),也分別對(duì)AC4在雞、雌雄SD大鼠體內(nèi)的藥代動(dòng)力學(xué)和AC4在雞體內(nèi)的口服生物利用度進(jìn)行了研究,獲得了AC4在雞和SD大鼠體內(nèi)的主要藥動(dòng)學(xué)參數(shù),為AC4后續(xù)研究打下了基礎(chǔ)。
[Abstract]:Chicken coccidiosis is a common parasite disease, especially Eimeria tenella and Eimeria poisoning, which will cause weight loss, resistance decline and high mortality. AC4 is a new type of triazine anti-coccidiosis compound synthesized and screened on the basis of the structure of the animal medicine in Shanghai, China Academy of Agricultural Sciences. Preclinical studies have shown that its anti-coccidiosis effect is excellent. It has broad spectrum and low toxicity. The aim of this study was to establish an analytical method for the determination of AC4 in plasma of chicken and SD rats, and to investigate the pharmacokinetics of high, medium and low doses of AC4 in both animals and the oral bioavailability of AC4 in chicken at 1.33mg/kg BW dose. The main pharmacokinetic parameters were obtained. In the UPLC-UV method for the determination of AC4 content in plasma of SD rats, ethyl acetate was used as the extraction solvent and totrezhulide sulfoxide as the internal standard. The gradient elution method was used, and the injection time of each sample was 20 min, the specificity of the method was good. The detection limit and the quantitative limit were 0.04 ~ 0.08 渭 g / mL, respectively, and the quantitative range of the standard curve was 0.08-80 渭 g / mL, and the linear equation was 0.091 x 0.001 ~ (-1) C ~ (2 +), the linear relationship was good, the recovery rate of the added standard sample was between 97.56-106.2%, within a day, The precision of day was less than 6.36; the samples were stable after at least 8 h at room temperature or three times of repeated freezing and thawing. The method was sensitive and accurate, and could be used to detect the AC4 content. AC4 in SD rats' plasma in pharmacokinetic experiments. The pharmacokinetics of three doses of 10 mg/kg BW in male and female Sprague-Dawley rats was investigated. The results showed that there was a dose-dependent relationship between the area under the drug time curve and the maximum blood drug concentration, and the maximum blood drug concentration was reached at 4-5 hours after administration. There were significant differences in pharmacokinetics of AC4 in SD rats with different sex and different dosage groups in biological elimination half-life, and there were obvious gender and individual differences in pharmacokinetics of AC4 in SD rats. In the UPLC-UV method for the determination of AC4 content in chicken plasma, ethyl acetate was used as the extraction solvent and totrezoli sulfoxide was used as the internal standard. The gradient elution method was used. The injection time of each sample was 10 min, the specificity of the method was good. The detection limit and quantification limit were 0.02n 0.04 渭 g / mL and 0.04-50 渭 g / mL, respectively. The linear equation was 0.094 x 0.002 渭 g / mL, and the linear relationship was good. The recovery rate of the added standard sample was 92.97-109.5%. The precision between day and day was less than 7.84. The samples were stable after at least 8 hours at room temperature or three times of repeated freezing and thawing. The method was sensitive and accurate, and could be used to detect the content of AC4. AC4 in chicken plasma in pharmacokinetic experiments. In this paper, the dose-dependent relationship between the area under the drug time curve and the maximum blood drug concentration was found, and the drug concentration reached the maximum concentration in the average of 4 hours after administration. There was no significant relationship between the half-life of biological elimination and the dosage of the drug, and the average half-life of elimination was 18.5 h, which was a slow elimination drug. In the bioavailability test of AC4, under the dosage of 1.33 mg/kg BW, the oral dose of AUC 0-t was 53.836 mg / L ~ (-1) h, and that of the intravenous group was 68.068 mg / L ~ (-1) h. The bioavailability of AC4 was 79.1 mg 路L ~ (-1) by calculating the absolute bioavailability formula F=AUCpo/AUCiv 脳 100. To sum up, the UPLC-UV methodology for the determination of AC4 in plasma of chicken and SD rats was established, and the pharmacokinetics of AC4 in chicken, male and female SD rats and the oral bioavailability of AC4 in chicken were also studied. The main pharmacokinetic parameters of AC4 in chicken and SD rats were obtained, which laid a foundation for further study of AC4.
【學(xué)位授予單位】：中國(guó)農(nóng)業(yè)科學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：S859.795

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 薛飛群;;抗寄生蟲藥物研究進(jìn)展[J];獸醫(yī)導(dǎo)刊;2007年09期

2 姜云云,范國(guó)榮,劉皋林;組合給藥在藥代動(dòng)力學(xué)高通量篩選中的應(yīng)用[J];國(guó)外醫(yī)學(xué).藥學(xué)分冊(cè);2005年01期

3 侯瑛倩;楊文嬌;吳振;江建梅;魯蕾;;酵母細(xì)胞壁多糖在養(yǎng)殖業(yè)上的研究應(yīng)用[J];北方牧業(yè);2013年18期

4 李佩國(guó);李蘊(yùn)玉;賈青輝;張艷英;張香齋;張文香;;抗雞球蟲病藥物及其耐藥性現(xiàn)狀[J];河北科技師范學(xué)院學(xué)報(bào);2011年04期

5 王t熈，

本文編號(hào)：1990693