發炎性腸道疾病 (Inflammatory bowel disease, IBD) 是一種成因複雜的自體免疫疾病，主要症狀有嘔吐、腹痛、腹瀉以及直腸出血等。目前 IBD的常規治療有手術以及藥物治療，然而前者往往會在切口處復發炎症；後者由於IBD病灶區域廣泛，所以難以確保藥物在炎症處可有效釋放。為此，本研究利用肛門塞劑給藥的方式，設計了一個產氣系統，藉由在腸道產生CO2氣體來對給藥環境進行擾動，因而形成藥物氣泡 (drug bubble)，可以有效地增大藥物與腸壁的接觸面積 (contact area)，以及增加藥物在腸道內的分散能力 (diffusion ability)。近年來硫化氫 (hydrogen sulfide, H2S) 氣體在生物體內作為信息傳遞物質的作用機制逐漸被解開，文獻指出H2S具有抑制發炎基因表達的能力,曾被用於胃炎、心肌炎、關節炎等炎症治療。在本研究中，我們選用可以產生H2S的疏水有機硫化物diallyl trisulfide (DATS) 作為減緩IBD發炎反應的治療藥物，並利用上述之膠囊產氣系統來達到有效分散DATS至腸道病灶部位之效果。在 in vitro 實驗中，我們分析了本系統產氣過程和氣泡結構，並發現氣泡可以增加DATS在腸道環境中的分散，且產氣系統可以提高其釋放藥物的細胞利用效率。在 in vivo 實驗中，我們建構了大鼠IBD模型，並發現相較於未治療及使用無產氣效果膠囊之組別，使用本膠囊產氣系統可以顯著地改善 IBD病徵，從腸道切片分析也可觀察到較良好的組織復原情形，對促發炎因子也有更好的抑制效果。此結果證實本系統能夠有效分散DATS並提高其細胞利用率，有助於緩和IBD發炎反應及達到良好的恢復結果。

Inflammatory bowel disease (IBD) is a group of inflammatory syndromes for the gastro-intestinal tract with the symptoms of abdominal pain, vomiting, diarrhea and rectal bleeding. Surgical and medical treatments are the principle therapies for IBD. However, inflammation often recurs at the resection site by surgical treatment. Furthermore, refers to the inflammatory area may occur in any position of the intestinal system, it’s difficult to release the drug at the specific targets. To deal with this problem, we had designed a foaming system via suppository delivery. The produced CO2 gas gave rise to create drug bubbles to extent the contact area between drug and bowel wall, and lead to increase drug diffusion in the intestinal tract. In recent studies, H2S was reported to mitigate inflammation by down-regulation of some pre-inflammatory genes, and was used in treating several kinds of inflammation. In this research, the hydrophobic H2S precursor diallyl trisulfide (DATS) was applied with the foaming system for IBD treatment. In the in vitro studies, it shows that the better DATS diffusion, the data also showed better cell utilization ability for the foaming group, compared to the w/o foaming group that cause a better anti-inflammation effects. In the in vivo studies of rat IBD model, it shows that the better recovery was observed for the foaming group than the no treatment and w/o foaming group by both the results of disease index record and histological H&E stain, along with a better down-regulation of some pre-inflammatory cytokines. These results validate our foaming system is benefit for DATS diffusion and cell utilization, which helps to anti-inflammatory and leads to good recovery of IBD.

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