蔡金川 義守大學

中西藥可否併用?如何併用藥物才會達到安全，有效降低副作用和毒性之系統分析迄目前為止尚無完整之數據可提供醫療參考。中藥配合現代醫療之輔助療法已深受世界之重視與許多研究亦發現其對疾病治療能提升疾病治癒率、緩和症狀或縮短病程，由此可提高治癒效益、改善病患疾痛及降低醫療成本。因此如何建立完善中西藥併用方法之相關安全資料，減少中西藥併用所生之毒性或造成血中藥物濃度過量之副作用，方可提升民眾就醫信心，增加癒後療效及對維護醫療品質均會有相當的助益並具正向的價值，更開啟臺灣醫療發展新頁。近年來有許多藥物中毒之報告，而將中毒怪罪於是中藥之毒性，此有待急需澄清中藥對人體之毒性印象。另民眾在慢性病及難治疾病常會接受中西醫治並同時服用中西藥或含中草藥之健康食品，令現在許多醫院也都開設中西醫聯合門診。然而其間之中西藥併用所生之毒性或副作用，迄今國內外之研究之草藥或單一之中藥，鮮有中藥方劑相關之文獻。

本計畫選擇台灣最常用之中藥方劑（衛生署公告之標準方劑100種）為準則。首期針對預防及治療血栓疾病的口服抗凝血劑（warfarin）第二年期則選定常用的消炎止痛藥（ibuprofen）為研究對象，進行中藥與人類血清蛋白結合能力之藥物定量分析。warfarin 與ibuprofen都會與血漿中之白蛋白（albumin）結合，因此，常會與競爭白蛋白結合則會使游離的warfarin與ibuprofen增加，warfarin將使得病人之凝血時間增長，進而造成出血的危險。另ibuprofen將使得藥物不良反應發生的機率提高如肝傷害。研究方式將以模擬人血清蛋白濃度於攝氏溫度37度分別將warfarin或ibuprofen及中藥方劑作用1小時，利用10 kDa 的分子篩分離游離態的warfarin（或ibuprofen）以高效能液相層析儀（HPLC）定性及定量。利用楊教授實驗室已建立多年之分析平台將可快速進行目前市售或常用之中藥方劑與西藥之交互作用分析。再選擇影響warfarin與人血清蛋白結合之中藥方劑，進一步利用螢光光譜分析探討中藥方劑影響warfarin與蛋白結合的變化。最後研究warfarin與中藥方劑併用時與蛋白質之結合能力在動物體內之吸收分佈、代謝排泄情形。及是否影響血小板功能或凝血功能，是否進而造成出血的危險產生不良影響?是否有藥物加乘、或相斥作用等反應?過量ibuprofen將造成肝傷害後續並利用動物模式研究中藥方劑與ibuprofen併用影響肝臟功能與代謝的關係。本研究結果將提供中藥方劑在臨床應用上與warfarin或ibuprofen併用所產生之交互作用和副作用資訊，將可預防或降低副作用以及減少藥害之發生。最後將實驗中選用的中藥方劑進行分類，主要分為婦科、小兒、老人與一般用藥，將實驗結果提供專業人員參考或是做為民眾的衛教手冊。

關鍵詞：中藥方劑、Wafarin、Ibuprphen、人類血清蛋白、中西藥物交互作用、快速分析平台、藥物動力學、血小板與血液凝集作用、cytochrome P450、肝功能、性別議題

Analysis of drug interaction between warfarin, ibuprofen and regular Chinese medicinal prescriptions in Taiwan (2-2)

Tsai, Chin-Chuan I-Shou University

Can we use the western drug and traditional Chinese medicinal prescriptions (TCMP) together? So far, there is not yet complete as of data can provide medical information which is efficient and reliable between western drugs and TCMP. How to arrange the different types of western drugs and concurrent with TCMP? And where can tell us it is safety, effective and low side effects and toxicity for out body systems? Chinese medicine and modern medical care has been well received adjuvant therapy can improve the treatment of diseases, alleviate symptoms or shorten the disease course, which can improve the healing benefits, reduce pain and patient’s illness medical costs. So, how to establish and improve the methods used in medicine and related safety information, and use of Chinese medicine to reduce toxic drug concentrations in blood or cause side effects overdose. To seek medical treatment only to enhance public confidence, increase efficiency and maintain good prognosis for quality of care they will have considerable help benefits and a positive value, but also open a new page in Taiwans medical development. Recent years, many reports of drug and herb interactions need to clarify the toxicity of TCMP on the body. We choose to focus on the common chronic diseases to see the impact on the human body that combined intake the TCMP and western medicine. Otherwise, the department of integrated Chinese and western medicine was established in many Hospital. The researches on the interactions between Weston drug and TCMP are rare. The studies were focus on the interaction between on one single herbal medicine and Weston drug. This project uses top-hundred of Chinese medicinal formulas (100 standard TCMP published by Department of Health, Executive Yuan, R.O.C.), and commonly used drug- warfarin and ibuprofen for analysis their drug herb interaction. In this study, we evaluated drugs interaction by carried out with human serum albumin (HSA) as our model which is a transfer protein and 90% mainly content of vascular system, drugs have to be bound with it before arrived at destination. So, a first, fast, and reliable analysis mode is setup to analyze the HSA binding capacity. It is reported that warfarin and ibuprofen could binding with HSA. If warfarin combined with TCMP which would affect human serum albumin, the concentration change of free form of wafarin would change the clotting time of patients. The side effect of ibuprofen combined with TCMP wound increase the injury of liver. Initial screening to a fixed concentration of HSA incubated at 37℃ which contained with warfarin or ibuprofen and TCMP for 1 hour, using 10 kDa molecular sieves for separation of the unbound form of warfarin or ibuprofen and determinate the qualitative and quantitative by HPLC. Therefore, the use of the laboratory analysis platform to quickly create commonly used TCMP is currently commercially available, or interaction of conditions to reduce the drugs on the human body under the unknown cause of toxicity. Besides, we use the method of fluorescence spectra to analysis the affect between warfarin and HSA. Furthermore, we choose the TCMP that affects the binding between warfarin (or ibuprofen) and HSA to analysis the absorption, distribution, and elimination of warfarin. Besides, the affect on platelet and blood coagulation function and the side effect will be analyzed. The animal model will be used to study on the injury of liver and the interaction between ibuprofen and TCMP. The results of this study will provide an information on drug interaction between warfarin or ibuprofen and TCMP and be success to determe the other criteria drugs for a better future, the detail information of medicines and other related protein binding parameters is valuable collected and referred. Finally, we will classify the TCMP into the major used of female, children, and the elderly. The data will be educated of general public and medical staff.