臺灣博碩士論文加值系統

本研究在比較健康的白肉雞與有色雞(黑羽土雞)單劑量口服（20 mg/kg bw）脫氧羥四環黴素(DC)配方藥粉的組織殘留分析。連續給藥5天後於六個時間點連續採集腦、心臟、肝臟、肌胃、腎臟、胸肉、血液、骨髓、腿肉等九種樣本，參照93年01月14日署授食字第0939300627號公告之「食品中動物用藥殘留量檢驗方法－四環黴素類抗生素之檢驗」檢測各組織中脫氧羥四環黴素濃度。
因此本研究目的在了解脫氧羥四環黴素於有色雞的組織殘留情形，並與白肉雞作比較。分析結果發現連續5天口服DC 20 mg/kg/day，於最後一次給藥12小時後，雞隻在肝臟、腎臟組織的DC濃度明顯較高於血漿中DC濃度，其餘腦、心臟、肌胃、胸肉、骨髓、和腿肉組織的DC濃度低於血漿中DC濃度；於各採樣時間點所測得組織中脫氧羥四環黴素濃度，普遍白肉雞濃度較黑羽土雞高。在停藥後，無論白肉雞或有色雞，組織中藥物殘留均明顯逐日下降，雖然停藥1-3天後，兩組的腦、肝、腎、骨髓之殘留濃度均較血漿高，但到第五天時，僅剩肝臟與骨髓測得殘留藥劑。進一步分析脫氧羥四環黴素在有色雞與白肉雞各組織殘留情形，在統計學上並無顯著的差異。
本研究結果顯示白肉雞及有色雞於腦、心臟、肌胃、腎臟、胸肉、血液、和腿肉等臟器通常於停藥後第3~4天即檢測不到DC之殘留、而在停藥後第5天，肝臟、骨髓仍可檢測出DC殘留，故在公共衛生上與現行停藥期之規定是相符的。
按行政院農業委員會動植物防疫檢疫局「動物用藥品使用手冊」脫氧羥四環黴素為核准使用之動物用藥品，但衛生署公告之「動物用藥殘留標準」，脫氧羥四環黴素於97年3月17日修正，增列在魚的肌肉部位殘留容許0.01ppm，其餘畜禽仍維持「不得檢出」。因脫氧羥四環黴素抗菌範圍廣、價格便宜及投藥的方便性，顯示其在家禽飼養階段被農戶廣泛使用且造成肉品及組織藥物殘留問題應當受到重視。

In this study we performed tissue residue analyses of Doxycycline, which are administered orally as powder formulae at a single dose of 20 mg/kg/day for consecutive 5 days on healthy broiler chickens and Taiwan native chickens, respectively. Tissue samples from 9 various sites, including the brain, heart, liver, gizzard, kidney, breast muscles, blood, bone morrow and thigh muscles were collected 12 hrs after Doxycycline withdrawal initially and then sampled every 24 hours for 5 days, concentrations of Doxycycline in these samples were measured, following the standardized procedures declared on 01-04-2004 by Food and Drug Administration(FDA), Department of Health, Executive Yuan.
The results reveal that, after oral administration of Doxyclcline at 20 mg/kg/day dose for 5 consecutive days, in both groups the tissue residue levels in liver and kidney recorded 12 hours after withdrawal were consistently higher than blood serum and those in brain, heart, gizzard, breast muscle, bone morrow and thigh muscles were lower than plasma level. The results of the sampling time points measured tissue Doxyclcline concentration, the concentration of the more common higher doxycycline tissue concentration in Broiler chicken than Taiwan native chicken.
After withdrawal, tissue residual level of Doxycycline are observed to decline rapidly: for the first 3 days, those in brain, liver, kidney and bone morrow remained higher than serum level, yet on the fifth days after withdrawal only liver and bone morrow have detectable residues.
In our study, although 5 days after withdrawal tissue residues in liver and bone morrow remained detectable, those in brain, heart, muscular stomach, kidney, blood and thigh muscles of both broiler and Taiwan native chickens have declined to a barely detectable level 3-4 days after its withdrawal, thus current regulation for a 5-day withdrawal is feasible from the viewpoint of public health concern.
In the “Manual of animal drug use”, published by Bureau of Animal and Plant Health Inspection and Quarantine, the use of Doxycycline is permitted in animal husbandry, yet in the”Criteria of animal drug residue”, Department of Health dictates no detectable residual Doxycycline for nearly all kinds of meat products on the market, with the exception of fish, of which the accepted concentration is 0.01 ppm in muscle tissue (amended on 03-17-2008).
Because of its broad antibacterial spectrum, low price and convenience to apply, Doxycycline is extensively used in animal husbandry, and the ensuing problems of drug residue deserve attention.

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誌謝………………………………………………………………i
中文摘要…………………………………………………………ii
摘要(英文)………………………………………………………iii
目次………………………………………………………………v
表目次……………………………………………………………viii
圖目次……………………………………………………………ix
第一章 前言……………………………………………………1
第一節 研究背景…………………… ………………………1
一、家禽產業之重要性……………………………………1
二、台灣的家禽產業………………………………………1
三、台灣土雞簡介…………………………………………2
(一)何謂台灣土雞………………………………………2
(二)台灣土雞分類………………………………………2
(三)台灣土雞經濟效益…………………………………2
四、土雞與白肉雞比較……………………………………3
五、市售畜禽產品之藥物殘留問題………………………4
第二節 畜禽產品藥物殘留原因及影響……………………5
一、藥物殘留定義……………………… ………………5
二、畜禽產品藥物殘留原因……………… ……………6
三、藥物殘留對人體之危害…………… ………………6
第三節 研究目的……………………………………………7
第四節 國內畜禽水產品藥物殘留之監測制度……………8
一、相關法規訂定……………………… ………………8
二、加強動物用藥品抽查取締…………… ……………8
三、強化畜牧場用藥品質監測…………… …………9
第二章 文獻探討……………………………………………10
第一節 抗菌藥物之發展、分類及抗藥性………… ……10
一、 抗生素發展…………………………………… …10
二、 抗生素分類……………………………… ………10
三、 抗生素抗藥性…………………………… ………10
第二節 四環徽素抗生素簡介……… ……………………11
一、 作用機制…………………………………… ……11
二、 藥物動力學……………………………………… 12
三、 副作用及毒性……………………………… ……12
四、 發展與應用…………………………… …………13
第三節 畜禽產品中藥物殘留檢驗技術之簡介…… ……15
一、 微生物抑制法………………………… …………15
二、 酵素連結免疫反應法………… …………………15
三、 高效液相層析法……………… …………………15
(一)高效液相層析之歷史…………………………………16
(二)高效液相層析之原理…………………………………16
(三)高效液相層析之分類…………………………………16
(四)高效液相層析系統主要裝置簡介…………………18
第四節 歷年國內畜禽產品藥物殘留與健康風險…… …20
第三章 材料與方法……………………… …………………22
第一節 實驗設計…………………………………………22
第二節 實驗動物及藥劑…………………………………22
第三節 藥物分析及儀器設備………………………… 22
一、 檢驗方法………………………… ………………22
二、 儀器設備及試劑配製………… …………………23
三、 標準溶液之配製…………………………… ……24
四、 C18 固相萃取匣之活化…………………… ……24
五、 檢液之調製……………………… ………………24
六、 鑑別試驗及含量測定……………………… ……25
七、 標準曲線之製作………………………… ………25
八、 添加回收率之試驗……………………… ………25
九、 偵測極限與定量極限之試驗…………… ………25
第四章 結果…………………… ……………………………26
第一節 脫氧羥四環黴素在白肉雞組織殘留……… ……26
第二節 脫氧羥四環黴素在黑羽土雞組織殘留……… …27
第三節 脫氧羥四環黴素在白肉雞與黑羽土雞組織殘留比較 27
第五章 討論…………………… ……………………………29
第一節 高效液相層析法之殘留分析……………… ……29
第二節 脫氧羥四環黴素在白肉雞與黑羽土雞組織殘留情形探 30
第三節 養殖牧場管理與藥物殘留之關聯性分析…… …………31
第四節 畜禽水產品藥物殘留與公共衛生之探討……… ………32
第六章 結論……… ………………………………………………34
第七章 參考文獻……………… ……………………………………64
第八章 附錄…………… ……………………………………………69

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