摘要

本研究目的在研發新的SACCHACHITIN劑型以方便使用於寵物皮膚外傷。我們以5%的CMC為基質加入10%的SACCHACHITIN製成軟膏狀的成品SAP10。動物實驗亦證實SAP10具有促進傷口癒合的功效。在大白鼠的皮膚生檢傷口癒合實驗以及燙傷實驗，傷口的組織病理變化、傷口面積、生長因子以及基質金屬型蛋白水解酶 (Matrix metalloproteinease, MMPs) 作為評估的項目。從組織病理以及傷口面積的改變，顯示SA P-10可以在癒合各期刺激分泌生長因子包括PDGF、TGF-β1以及VEGF的表現，同時也能抑制MMP-9以及依據分子量推測為MMP-2的表現。
另外在犬的燙傷實驗，由組織病理變化以及MMPs的表現分析，同時支持SAP10具有促進傷口癒合的功效。由於具有犬專一性的生長因子檢驗無法購得或製成而無法分析生長因子的表現。
在犬隻及大白鼠實驗中MMPs的表現呈現不一致的情況或許和動物種的差異有關，而生長因子不同的表現於大白鼠全層皮膚切除以及燙傷實驗或許和傷口形成的原因有關。
SAP10具有外型可塑性以及延展性的特性，無論毛髮的干擾均可與傷口充份接觸，也容易以繃帶包紮使敷料穩固於動物傷口，達到治療的目的。
本研究結論為SAP10對於全層皮膚切除以及全層皮膚燙傷之傷口具有良好的傷癒合口促進的功效以及臨床使用的方便性。

Summary

The aim of the present study was to develop a new type wound dressing derived from SACCHACHITIN to meet the demands of pets. SACCHACHITIN P10 was composed of 10% SACCHACHITIN and 5% Carboxymethyl cellulose sodium salt (CMC). Animal models were employed to confirm the effectiveness of wound healing enhancement of SAP10. Skin biopsy full thickness excision and full thickness thermal burn were created on the back of Wistar rats and size of wound area, histopathological changes, growth factors matrix metalloproteinases (MMPs) contents were measured in the wound areas. The histopathological change and wound area revealed that SAP10 promote growth factors including PDGF, TGF-β1 and VEGF expression and that in good agreement with the healing process of inflammation, proliferation and remodeling in the model of full thickness excision. In the same time the activities of MMP-9 and presumed MMP-2 were found to be suppressed.
In dog, experiment on thermal burn trauma was also carried out. Histopathological and wound area changes support that SAP10 was effective in accelerating wound healing. Zymographic results demonstrated that SAP10 suppressed MMP-9 and MMP-2 during the whole process of healing. However, growth factors specific for canine were unavailable that this part of data was devoid.
The different expression of MMPs in rat and dog might be because of species difference. The wound type also affected the expression of growth factors in the wound area.
SAP10 was in a viscous and amorphous paste form and it was able to be applied onto the wound of any animal surface with any shape for a stable bandage no matter with hair or not.
In conclusion, SAP10 is an effective wound healing formulation to meet the special demands of pets for full thickness excision and full thickness thermal wound.

目 錄

中文摘要....................................... i
Abstract ..................................... ii
第壹章、緒論.................................... 1
壹、背景..................................... 1
貳、目的..................................... 1
叁、前人研究 ................................ 2
ㄧ、寵物皮膚生理 ......................... 2
二、寵物皮膚創傷生理 ...................... 3
三、皮膚癒合過程.......................... 4
(一) 急性炎症期 ...................... 4
1、急性炎症期早期 .................. 5
2、急性炎症期晚期 .................. 6
(二) 增生或肉芽組織形成期 ............. 6
1、纖維增生 ........................ 7
2、創口收縮 ........................ 7
3、血管新生 ........................ 7
4、表皮新生 ........................ 8
(三) 組織重組期 ....................... 8
肆、寵物燙傷................................... 9
ㄧ、引起燙傷的原因 ........................ 9
二、臨床症狀 ............................ 10
三、組織病理 ............................. 11
四、治療 ................................. 11
伍、獸醫傷口癒合學............................ 11
陸、SACCHACHITIN ............................ 13
一、敷料原料SACCHACHITIN的來源 ............. 13
二、利用SACCHACHITIN作為生物醫學材料 ........ 13
三、靈芝萃取物促進傷口之癒合................. 14
四、CHITIN的特性 .......................... 14
(一) 生物相容性 .......................... 14
(二) 生物降解性 .......................... 14
(三) 免疫刺激作用 ........................ 14
(四) 加速傷口的癒合 ...................... 15
五、研究傷口癒合的評估方式 .................. 15
(一) 基質金屬型蛋白水解酶.................. 16
(二) 生長因子 ............................ 18
柒、本研究的評估方式選擇........................ 20
一、MMPs ................................. 20
二、生長因子 ............................. 20
三、皮膚組織病理 ......................... 20
四、傷口面積的計測 ........................ 21
捌、SACCHACHITIN對寵物之先期研究............... 21
玖、實驗假說.................................. 22
第貳章、材料與方法............................... 25
壹、實驗架構................................... 25
貳、材料...................................... 26
一、原料 ..................................... 26
二、實驗動物 .................................. 26
三、麻醉劑 ................................... 26
四、化學試劑 ................................. 26
五、敷料 ..................................... 26
叁、設備...................................... 27
肆、敷料製備方法............................... 27
一、粉末SACCHACHITIN傷口敷料的製備 .........27
二、SACCHACHITIN P-10的製作............... 28
伍、動物實驗................................... 28
一、實驗動物 .................................. 28
二、麻醉藥 .................................. 29
三、麻醉劑劑量及給藥法 ........................ 29
四、傷口製造 ................................. 30
五、觀察及取樣 ............................... 31
陸、臨床病例治療與觀察......................... 36
第參章、結果與討論 ............................. 38
壹、SACCHACHITIN P-10 (SAP10) ............... 38
貳、大白鼠皮膚傷口癒合實驗 ..................... 39
叁、大白鼠燙傷實驗............................. 55
肆、犬燙傷實驗................................ 67
伍、犬臨床病例................................ 76
第肆章、結論.................................... 82
參考文獻....................................... 84

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