臺灣博碩士論文加值系統

連續 28 天口服投予 Sprague-Dawley (SD) 大鼠固態栽培牛樟芝子實體 (WS027)、固態培養牛樟芝菌絲體 (GS100) 或液態發酵牛樟芝菌絲體 (SB011)，藉以評估不同製程的牛樟芝產品是否對大鼠具有亞急毒性。

SD 大鼠共 80 隻，依隨機方式分為四組 (每組雄、雌各十隻)，分別為對照組、WS027、GS100 或 SB011 藥劑處理組。藥劑分別投予 3000 mg/kg/day 之 WS027、GS100 或 SB011 之0.5 % CMC 懸浮液，對照組則投予 0.5 % CMC 水溶液 (對照溶液)。3 個藥劑處理組及對照組之投予體積均為 15 mL/kg。
試驗評估項目依據衛生署藥品非臨床試驗安全性規範 (DOH, 2000)，項目包括動物外觀、臨床症狀、死亡率、體重成長/體重增加、食物攝取量、眼睛檢查、臨床病理 (尿液、血液及血清生化)、肉眼病變、臟器重量、臟器與體重比值及組織病理鏡檢。
結果顯示：WS027、GS100 或 SB011 經重複口服投予 28 天後，並不會造成任何動物的死亡；WS027、GS100 或 SB011 藥劑處理組之體重與體重成長均與對照組相似；所有組別之平均飼料攝取量、臟器重量及臟器對體重比值，均無因試驗物質處理的不同而有差異；各藥劑處理組與對照組於臨床病理學並未發現相關變化。

病理檢查除了造成十二指腸黏膜上皮極微至輕度增生與肥大外，不會造成大鼠任何與試驗物質處理相關或顯著之毒性變化或病變，惟考慮十二指腸黏膜上皮之變化尚屬輕微，不認為是顯著的毒性反應。藉由本試驗結果顯示，以劑量 3000 mg/kg 固體栽培樟芝子實體 (WS027)、固態醱酵樟芝菌絲體 (GS100) 或液態醱酵樟芝菌絲體 (SB011) 經連續投予SD大鼠 28 天，均未造成任何毒性症狀或試驗物質處理相關之變化，故以每日人體建議劑量 (2000 mg/day) 之 15倍 (物種代謝率折算)，仍不會造成動物毒性。

This study is to evaluate the sub-acute toxicity by administrating the extract of solid cultivation fruiting bodies (WS027), solid-state culture mycelium (GS100) or submerged culture mycelium (SB011) of Taiwanofungus camphoratus for consecutive 28 days via oral gavage in Sprague-Dawley (SD) rats.
Eighty Sprague-Dawley (SD) rats will be allocated randomly into four groups (ten males and females per group), including a control group and three treatment groups. Treatment group will be administrated at 3000 mg / kg / day of WS027, GS100 or SB011 suspension, and the control group will be administrated 0.5% CMC solution (control solution). Dosing volume was 15 mL / kg.
Experimental evaluation (DOH, 2000) included the results of the animal appearance, clinical signs, mortality, body weight, food consumption, clinical pathology (urine, blood, and serum biochemical), gross lesions, organ weight, relative organ weight and histopathological examination.
All animal survived to the end of the study. They are similar in body weight and weight growth between the treatment and control groups. No treatment-related changes in food consumption, organ weight, and related organ weight among all groups. No related changes were found in clinical pathology of all groups.
Necropsy and histopathological examination indicated no treatment-related gross lesions. Only minimal to mild hyperplasia and hypertrophy in duodenal mucosal epithelium was observed. However, the change in the duodenal mucosa epithelium is minor and won’t be considered toxic effect.. No toxic signs or treatment-related changes were observed by administrating the extract of solid cultivation fruiting bodies (WS027), solid-state culture mycelium (GS100) or submerged culture mycelium (SB011) of Taiwanofungus camphoratus for consecutive 28 days via oral gavage in Sprague-Dawley (SD) rats. Therefore, it will not cause animal toxicity by administrating15 times of recommended human daily dose (2000 mg / day).

謝誌 I
中文摘要 II
Abstract IV
目錄 V
表目錄 VII
圖目錄 VIII
第一章 緒論 1
1.1 前言 1
1.2 牛樟芝命名 2
1.3 牛樟芝效用 2
1.4 三萜類 3
1.5 多醣體 4
1.6 牛樟樹 4
1.7 牛樟樹復育 5
1.8 牛樟芝人工培育 5
1.9 牛樟芝的藥理作用 7
1.10 健康食品管理法 12
1.11 安全性評估 13
1.12 血清生化分析及臨床意義 13
1.13 研究動機 17
第二章 實驗材料、設備與方法 18
2.1 實驗材料、試藥 18
2.2 試驗物質 18
2.3 設備 19
2.4 試驗動物 20
2.5 方法 21
2.5.1 動物試驗設計 21
2.5.2 劑量選定 22
2.5.3 投予途徑 22
2.5.4 試驗觀察及記錄 23
2.5.5 臨床病理檢驗 24
2.5.6 動物解剖 26
2.5.7 組織切片製作與病理學評估 29
2.6 統計分析 31
第三章 結果與討論 32
3.1 動物死亡率、眼睛檢查及臨床觀察 32
3.2 體重變化 32
3.3 食物消耗量 33
3.4 臨床病理 39
3.4.1 尿液檢驗 39
3.4.2 血液檢驗 39
3.4.3 血清生化分析 44
3.5 屍體解剖與肉眼檢查 49
3.6 臟器重量 49
3.7 組織病理學 52
第四章 結論 54
第五章 參考文獻 56

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