發(fā)布時(shí)間：2018-04-23 18:14

  本文選題：頭孢噻呋鈉 + 高效液相色譜法��； 參考：《山東農(nóng)業(yè)大學(xué)》2017年碩士論文

【摘要】：二十世紀(jì)八十年代,美國(guó)法瑪西亞-普強(qiáng)公司(PharmaciaUpjohn)開(kāi)發(fā)了畜禽專(zhuān)用頭孢菌素,即頭孢噻呋(Ceftiofur),又名賽得福。頭孢噻呋為第三代頭孢菌素,抗菌機(jī)理是通過(guò)抑制細(xì)菌細(xì)胞壁的合成導(dǎo)致細(xì)菌死亡,頭孢噻呋對(duì)鏈球菌的抗菌作用比氟喹諾酮類(lèi)藥物強(qiáng),抗菌活性?xún)?yōu)于氨芐西林。頭孢噻呋自誕生以來(lái),因其具有抗菌譜廣,抑制或殺滅病原微生物的能力強(qiáng),毒副作用低,殘留少等優(yōu)勢(shì),獲得世人的認(rèn)可接受,頭孢噻呋被批準(zhǔn)應(yīng)用于動(dòng)物細(xì)菌性疾病的治療。自1988年以來(lái),頭孢噻呋鈉先后被北美、歐洲一些國(guó)家及日本正式批準(zhǔn)用于豬、羊、奶牛、肉牛、馬的呼吸道疾病治療和寵物感染性疾病的防治。目前,我國(guó)家禽養(yǎng)殖已走向規(guī)�；�,養(yǎng)殖密度大、環(huán)境差,易導(dǎo)致畜禽傳染性疾病流行和爆發(fā),由此可能引發(fā)禽類(lèi)大批量出現(xiàn)疫情甚至死亡的現(xiàn)象,將會(huì)給養(yǎng)禽業(yè)造成巨大損失。頭孢噻呋鈉作為動(dòng)物專(zhuān)用的一種新抗生素,在一定程度上解決了養(yǎng)禽場(chǎng)細(xì)菌性疾病所引發(fā)的問(wèn)題。隨著國(guó)內(nèi)企業(yè)成功合成頭孢噻呋鈉并大批量生產(chǎn),其合成原料成本不斷降低,頭孢噻呋鈉在獸藥領(lǐng)域?qū)⒌玫礁訌V泛的應(yīng)用。與此同時(shí),對(duì)于頭孢噻呋鈉能否在不同種屬畜禽體內(nèi)得到科學(xué)、合理和安全的應(yīng)用,也將此藥在多種動(dòng)物體內(nèi)外的研究引向深入。通過(guò)運(yùn)用高效液相色譜法(HPLC)檢測(cè)麻雞體內(nèi)頭孢噻呋鈉的濃度,研究頭孢噻呋鈉在麻雞體內(nèi)的藥動(dòng)學(xué)行為,從而清晰的判斷和了解頭孢噻呋鈉在麻雞的機(jī)體內(nèi)ADME過(guò)程,同時(shí)能夠更加科學(xué)的確定頭孢噻呋鈉的給藥途徑、給藥時(shí)間,建立測(cè)定頭孢噻呋鈉的藥代動(dòng)力學(xué)及組織分布的研究方法,從而為臨床上安全、合理的用藥,以及制定休藥期、防止藥物殘留提供參考。試驗(yàn)分別采用口服和肌肉注射的給藥方式研究頭孢噻呋鈉在麻雞體內(nèi)的藥動(dòng)學(xué)過(guò)程,給藥后不同的時(shí)間點(diǎn)進(jìn)行麻雞翅下靜脈采血,采用HPLC對(duì)血漿樣品和組織樣品進(jìn)行頭孢噻呋鈉原型藥物的檢測(cè)分析,對(duì)頭孢噻呋鈉在麻雞體內(nèi)的藥代動(dòng)力學(xué)特點(diǎn)進(jìn)行研究、對(duì)頭孢噻呋鈉在麻雞體內(nèi)的生物利用度進(jìn)行分析。通過(guò)對(duì)頭孢噻呋鈉在麻雞體內(nèi)的藥代動(dòng)力學(xué)測(cè)定研究發(fā)現(xiàn),對(duì)麻雞經(jīng)肌注給予頭孢噻呋鈉20 mg/kg的原型藥代動(dòng)力學(xué)參數(shù):血漿達(dá)峰濃度Cmax為(6.337±3.29)μg/mL,達(dá)峰時(shí)間Tmax為(0.25±0.00)h,消除半衰期t1/2為(0.851±0.23)h,消除速率常數(shù)Ke為(0.883±0.32)h-1,AUC0-t為(5.338±2.85)μg·h·mL-1,AUC0→∞為(5.417±2.87)μg·h·mL-1,平均滯留時(shí)間MRT為(0.837±0.07)h,清除率CLtot為(72.950±28.53)m L·min-1·kg-1,表觀(guān)分布容積Vd為(5.250±2.20)L·kg-1。麻雞肌注頭孢噻呋鈉在其組織中未檢測(cè)到頭孢噻呋鈉原型藥物。通過(guò)對(duì)麻雞口服給予頭孢噻呋鈉20 mg/kg的藥動(dòng)學(xué)研究發(fā)現(xiàn):麻雞口服頭孢噻呋鈉在其血液及組織均未檢測(cè)到頭孢噻呋鈉原型藥物,表明頭孢噻呋鈉口服不吸收。
[Abstract]:In 1980s, the American The Upjohn Company (PharmaciaUpjohn) developed livestock and poultry cephalosporin, namely ceftif (Ceftiofur), also known as ceftif. Ceftif is the third generation cephalosporin. The antibacterial mechanism is to inhibit bacterial death by inhibiting the synthesis of bacterial cell wall, and the antibacterial action of ceftif to Streptococcus Fluoroquinolones are strong and antibacterial activity is superior to ampicillin. Since its birth, ceftif has been accepted by the world because of its strong antibacterial spectrum, strong ability to inhibit or kill pathogenic microbes, low toxicity and few residues. Ceftif has been approved for the treatment of bacterial diseases in animals. Since 1988, ceftif TIF sodium has been officially approved by North America, some European countries and Japan for the treatment of respiratory diseases of pigs, sheep, cows, beef cattle, horses and the prevention and treatment of infectious diseases of pets. At present, poultry breeding in China has become large-scale, the density is large and the environment is poor, which may lead to the epidemic and outbreak of infectious diseases of livestock and poultry, which may cause a large number of poultry. The occurrence of epidemic situation and even death will cause great loss to poultry industry. As a new antibiotic, ceftif sodium has solved the problems caused by bacterial disease in poultry farm to a certain extent. With the successful synthesis of ceftif sodium in domestic enterprises and mass production, the cost of synthetic raw materials is decreasing. Ceftif sodium will be more widely used in the field of veterinary medicine. At the same time, the scientific, rational and safe application of ceftif sodium in different species of livestock and poultry is used, and the study of the drug in and out of a variety of animals is also introduced. The use of high performance liquid chromatography (HPLC) for the detection of ceftif sodium in the chicken body Concentration, study the pharmacokinetics of ceftif sodium in the chicken, so as to clearly determine and understand the ADME process in the body of ceftif sodium in the body of the chicken. At the same time, it can be more scientific to determine the route of administration of ceftif sodium, the time of administration, and establish a method for the determination of the pharmacokinetics and tissue distribution of ceftif sodium, and the method of the study of the pharmacokinetics and tissue distribution of ceftif sodium. The pharmacokinetic process of ceftif sodium in hemp chicken was studied by oral and intramuscular injection, and the plasma samples and tissue samples were taken by HPLC in different time points after the administration of ceftif sodium in the chicken. The pharmacokinetic characteristics of ceftif sodium in hemp chickens were examined and analyzed. The bioavailability of ceftif sodium in hemp chickens was analyzed. The pharmacokinetics of ceftif sodium in hemp chickens showed that ceftif sodium was given 20 m of ceftif sodium to the intramuscular injection. The prototype pharmacokinetic parameters of g/kg: the plasma peak concentration Cmax is (6.337 + 3.29) mu g/mL, the peak time Tmax is (0.25 + 0) h, the elimination half life t1/2 is (0.851 + 0.23) h, the elimination rate constant Ke is (0.883 + 0.32) H-1, AUC0-t is (5.338 + 2.85) mu g, H. 7) h, the clearance rate of CLtot was (72.950 + 28.53) m L. Min-1. Kg-1, the apparent distribution volume Vd was (5.250 + 2.20) L. Kg-1. intramuscular injection of ceftif sodium in its tissue did not detect ceftif sodium prototype drug. The pharmacokinetics of ceftif sodium 20 mg/kg in the oral chicken was studied: the oral ceftif sodium in hemp chicken was in its blood and group. No cefotaxime sodium was detected in the prototypes, indicating that cefuroxime sodium was not absorbed orally.

【學(xué)位授予單位】：山東農(nóng)業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：S859.7

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