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題名 | 建立臺灣常用中藥方劑與阿司匹靈交互作用快速分析平臺=High-throughput Analysis of Drug Interaction between Aspirin and 100 Regular Chinese Medicinal Prescriptions in Taiwan |
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作者 | 蔡金川; 楊玲玲; Tsai, Chin-chuan; Yang, Ling Ling; |
期刊 | 行政院衛生署中醫藥年報 |
出版日期 | 20141200 |
卷期 | 光碟版3 2014.12[民103.12] |
頁次 | 頁(43)1-(43)43 |
分類號 | 413.4 |
語文 | chi |
關鍵詞 | 中藥方劑; 水楊酸; 中西藥合併; 血清蛋白; 藥物定量; 快速平臺; Chinese prescription; Salicylic acid; Drug and herb; Serum albumin; Binding dose; High-throughput platform; |
中文摘要 | 中西藥可否併用?如何併用藥物才會達到安全,及有效降低副作用和毒性之系統分析迄目前為止尚並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證實對疾病治療能有助於提升治癒率、緩和症狀或縮短病程,同時亦可提高治癒效益、改善病患疾痛及降低醫療成本,但是中西藥併用時造成血中藥物濃度過量之副作用是目前臨床最常發生之問題。臨床中醫治病用藥以方劑為主,目前由文獻搜尋未發現有相關論文報告,為增加癒後良效及維護醫療品質及增加民眾就醫信心,則有待建立中西藥併用交互作用之快速藥物分析平台,並架於中藥用藥安全網以提供並維護給世界上使用中醫藥之安全醫療資訊,更開啟臺灣中醫藥醫療安全實證醫學發展之新頁。 建立快速藥物分析平台是本計畫之首要目的,選擇以慢性疾病常用西藥與中藥併用對人體之影響為目標,利用人類血清運輸蛋白結合能力分析臨床中西藥物併用是否影響血清濃度之改變。本研究計畫採用行政院衛生署中醫藥委員會公佈之 100種基準中藥方劑(如:常用之加味消遙散、六味地黃丸、香砂六君子湯、葛根湯等),將透過健保局醫療資料來分析中西藥併用之頻率,研究對象以西藥水楊酸類藥物 aspirin,其為經常使用之止痛藥,並且異常被使用作為預防心臟病發生。本計畫進行 100種基準中藥方劑影響 aspirin與人類血清蛋白結合能力之藥物定量分析。 口服 aspirin經過人體吸收時,代謝成為水楊酸 (salicylic acid, SA),並迅速分佈至全身組織及體液,包括胎兒組織,乳汁及中樞神經。本計畫利用共同主持人楊玲玲教授實驗室建立多年之分析平台,已進行 aspirin經由動物體內代謝之生化變化以及高效能液相層析儀 (HPLC)定性及定量的試驗。同時本計畫則確立體外試驗之條件,體外試驗以特定濃度的血清蛋白於攝氏溫度 37度與 aspirin代謝物 SA及 100種基礎中藥方劑作用,利用 10 kDa的分子篩分離 SA,再以高效能液相層析儀 (HPLC)定性及定量,佐以熱力學偵測儀 (isothermal calorimeter, ITC)偵測結合物與血清蛋白之結合率再次驗證實驗結果。 依中醫藥委員會公布之 100種基準中藥方劑進行各處方之調劑、煎煮、冷凍乾燥及以 UV-VIS spectrum建立各方劑之標準指紋圖譜。接著建立快速分析平台,本實驗以 aspirin代謝物 SA進行分析。以 HPLC定量分析 100種基礎中藥方劑影響 SA與血清蛋白結合能力,發現成分不同之中藥方劑組成分會影響 aspirin與血清蛋白之結合率,結果增加結合率 20%以上的方劑有 6種,而增加 20%以下的方劑有 37種;有 54種方劑會減少 SA與血清蛋白結合,減少 20%以上的方劑有 5種,其餘皆為減少低於 20%的方劑。選擇常用方劑四物湯為例進行血清蛋白結構螢光變化與 ITC之分析,在螢光變化與 ITC結果發現中藥方劑可影響 SA與血清蛋白之結合,其結果與經 HPLC分析結果相符合。 以上結果證實本分析平台之可行性,將可作為快速分析參考,同時分析中藥方劑影響 SA與血清蛋白結合能力之數據亦可提供給臨床用藥參考以降低藥物多重及多樣性使用,減少對人體在未知下造成的毒性與副作用之產生。特別是中藥方劑改變藥物對血清吸收影響之機制分析,將可解析 aspirin與中藥方劑併用時在臨床醫療效果上是否產生不良影響 ?是否有藥物加乘、或相斥作用等反應?本研究結果對中藥方劑在臨床應用上將可預防或降低副作用以及減少藥害之發生。另外,具有改變藥物對血清吸收影響之中藥方劑,未來將逐一進行藥物動力及藥效之研究。 |
英文摘要 | Can we use the western drug and traditional Chinese medicinal prescriptions together? So far, there is not yet complete as of data can provide medical information which is efficient and reliable between western drugs and Chinese medicinal prescriptions. How to arrange the different types of western drugs and concurrent with Chinese medicinal prescriptions? 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 HSA 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 Taiwan's medical development. Recent years, many reports of drug interactions need to clarify the toxicity of traditional Chinese medicine on the body. We choose to focus on the common chronic diseases to see the impact on the human body that combined intake the traditional Chinese medicine and western medicine. To use of human serum albumin binding capacity of transport system, and its change of drug dose would be the observed point to concern the free form drug concentration in the serum, and to establish a rapid analysis platform is our goal. Firstly, selected the program used on patients who with chronic cardiovascular problems, thrombosis, inflammation and pain in “aspirin” medication and discuss this drug used with the commonly Chinese medicinal prescription interactions and possible mechanisms to provide Chinese and western medicine uses of security information. Therefore, to setup a rapid drug analysis platform is the primary aim of this project. This project uses the last three years prior to outpatient prescriptions which top-hundred of Chinese medicinal formulas (such as: Pingwei, Xiangsha Liujunzi soup, flavored Xiaoyaosan, Chaihuguizhi Tang, Xiao Chai Hu Tang, etc. a total of 100 species) together with NHI and medical information to understand and use the frequency with western medicine is our concerned cross-interaction prescriptions. Therefore, we focus on people who got chronic cardiovascular disease in the begining and we realized the salicylic acid (Aspirin) drug used in common. 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. Aspirin is often by oral medication, and it is the rapid and complete absorption after oral administration of about 80-100%, it will be decomposed and hydrolysed into salicylic acid form when it is in the absorption part. It is reported that aspirin could rapidly distributed to body tissue and body fluids, including fetal tissue, breast milk, and central nervous system. The protein binding ratio of salicylic acid salts is regard on the concentration dependent, such as almost 100 μg/mL HSA when 90%, 400 μg/mL HSA when 76%. The salicylic acid poisoning happened when symptoms occur, such as tinnitus, the plasma concentration raised and dose over 200 μg/mL, if the dose goes to 400 μg/mL, there will be more severe toxicity. Initial screening to a fixed concentration of HSA incubated at 37℃ which contained with aspirin and Chinese medicinal prescriptions (200 μg/mL) for 1 hour, using 10 kDa molecular sieves for separation of the unbound form of aspirin and determinate the qualitative and quantitative by HPLC. Therefore, the use of the laboratory analysis platform to quickly create commonly used Chinese medicinal prescription is currently commercially available, or interaction of conditions to reduce the drugs on the human body under the unknown cause of toxicity. It will be success to determine the other criteria drugs for a better future, the detail information of medicines and other related protein binding parameters is valuable collected and referred. View of the result, we foumd some of the Chinese Medicinal prescriptions and aspirin interactions manners. In the future, we will more study the PK and PD of each teraction priscriptions. |
本系統之摘要資訊系依該期刊論文摘要之資訊為主。