應用中藥治療骨骼肌損傷之研究

Studies on the Remedy of Skeletal Muscle Injuries Treated with Chinese Medicine

肌肉損傷，包括：肌肉拉傷、勞傷、肌肉挫傷、遲發型肌肉酸痛、及血腫等，皆是運動員與勞動者時常發生的肌肉傷痛問題。西方醫學對肌肉損傷常使用非固醇類消炎止痛劑與皮質類固醇或同化類固醇治療，然而也常因嚴重的副作用導致更嚴重的併發症。在中國傳統醫學中，利用中藥調合之膏劑及洗劑早被使用於跌打損傷之治療並且有一定的療效。然而此類傳統製劑因缺乏科學驗證，且因不良的外觀、色澤及異臭而不被西方人士接受。本研究以藥劑學技術將傳統用於治療肌肉損傷的方劑製備成現代穿皮吸收劑型，經由「挫傷動物模式」以藥理學、生理學、病理組織學等科學方法驗證其藥效，以期開發能廣被接受的新劑型。方法：首將由傳統醫療業者提供之有效驗方（含黃連、黃柏、黃苓、白芷、紅花、生地、骨碎補、乳香、沒藥）以酒精－－水混合溶劑萃取，經低溫減壓濃縮及冷凍乾燥成粉末，再以藥劑學技術將之調製成Simpleointement, W/O cream, FAPG base, Gel base等四種型態之經皮吸收軟膏劑型(1% w/w)。採用Yie W. Chien裝置以評估此四種型態軟膏劑型之體外穿皮吸收之能力，選用吸收最佳之劑型進行動物實驗。實驗動物模式採用Crisco開發之重鎚落下技術(Drop-mass technique)之挫傷模式，引起大白鼠腓腸肌損傷，經塗抹藥膏一定時間（一天一次共一星期）後，以測量浮腫體積、Laser droppler血流測定儀及組織切片等科學方法驗證治療前後之差異。由研究結果顯示，原計畫所擬調製之各種製劑之經皮穿透效果並不理想，另以精製芝麻油為基劑所調製之乳霜劑型則有較佳之穿透度。經上述各種方法實驗結果，雖然中藥製劑能有效減輕受挫傷動物之症狀，然而其療效仍不及市售已知具有消炎止痛療效之Indomethacin cream，因此，如擬以中藥處方製成西藥劑型應用於治療挫傷，仍有待在劑型之設計與有效成分之萃取定量上多加努力。

Muscle injuries, including stretch-induced muscle injuries, strains, muscle contusion, delayed-onset muscle soreness (DOMS) and hematomas, are muscle traumatic problems which often occurred to athletes and labors. In the western medicine, NSAIDs and corticoids or anabolic steroids are frequently used for the treatment of muscle injuries. However, severe side effects can also lead to the intolerant complications. As to the traditional Chinese medicine, some paste, ointment or lotions prepared from Chinese herbs have been used topically for the remedy of the related syndromes for millennia and proved to be effective. Nevertheless, they are not frilly accepted by the western people or even the Chinese people, due to the ugly appearances and unpleasant odors, and also, lack of scientific evidences. The present study has prepared four transdermal dosage forms of traditional Chinese herbs with modern pharmaceutical techniques to treat skeletal muscle injuries. Furthermore, the effectiveness will be validated with pharmacological, physiological and histopathological, using ”Drop-mass technique” published by Crisco, et. al. as the animal model. The aim of this study is to develop a new transdermal dosage form of Chinese medicine, expecting to be widely accepted in the international market. Methods: Initially, an effective experienced formula that consists of Coptidis rhizoma, Phellodendri cortex, Scutellariae radix, Pai-chi radix, Carthami fibs, Rehmanniae radix, Olibanum, Myrrha and Drynaria fortunei will be extracted with alcohol-water (1:1), the extract will be concentrated under reduced pressure at low temperature and then lyophilized. The lyophilized powder will be prepared to be simple ointment, W/O cream, FAPG base, and Gel base transdermal dosage forms. The transdermal delivery capacities will be evaluated with the Franz diffuse cell, and the best one among the four formularies will be selected as the target sample for the animal experiments: 1.0 gm of the dosage will be applied topically once a day for one week on the posterior surface of the gastrocnemius muscle in one limb of Wistar rats, where is the site that a single impact has been delivered from an instrumented drop-mass technique (mass, 171 g; height, 102 cm; spherical radius, 6.4 mm) and injured. The effectiveness on healing of injured tissue will be evaluated by measuring the edema volumes, microvascular circulation by Laser Doppler Perfusion Analyzer, as well as tissue histological examinations. The results of evaluating the transdermal capacities showed that the four preparations designed as in the protocol did not penetrate well through skin, and another cream based on purified sesame oil was then prepared and showed better penetrating ability. This preparation was used for the tests during this study. The results of therapeutic evaluation indicated that, although the sesame oil-based cream of Chinese herbs formula could fairly reduce the contused syndromes, however, it was not superior than that of Indomethacin cream, a well known anti-inflammatory agent, in the therapeutic efficacy. Therefore, in conclusion, the attempt to prepare a transdermal preparation to replace the ”western drugs” for the treatment of contusion syndromes, a lot of works should be done in the coming days, including formula design, the extraction techniques and quantitative analysis of efficacious components from herbs.