傳統硬膏劑安全性評估：黃丹（Pb3O4）鉛之釋出及穿皮吸收之研究

Safety Evaluation of Traditional Chinese Hard Plaster Studies on the Release and the Transdermal Absorption of Lead from Minium (Pb3O4)

傳統中藥硬膏劑在華人世界已廣被使用超過千年，惟此傳統製劑之製程中常需使用麻油與黃丹（成分以Pb3O4為主）一起加熱熬煮多時。本研究旨在探討貼敷由黃丹所熬煮製成之硬膏劑，是否可能因鉛之釋出經皮膚吸收進入血液循環，進而導致鉛中毒的危險。
本研究首先以溶離度試驗法觀測鉛自硬膏劑中釋離之情形，結果發現在24小時內並無任何鉛的釋出，顯示傳統上熬製硬膏劑所添加之黃丹以穩定的狀態結合在膏體內。隨後以紐西蘭兔為實驗動物，將硬膏劑貼於其腹部，在貼敷硬膏劑之前、後，於一定時間點採血，進行血中鉛濃度之分析。結果發現受試之紐西蘭兔在未貼硬膏劑前，全血中鉛之平均濃度為85.48 ± 24.72 ppb，而於貼硬膏劑後1小時，全血中鉛之平均濃度即上升至173.51 ± 36.81 ppb，至第30小時仍維持在78.52~171.94 ppb。
根據美國ACGIH的推薦，人體血中鉛濃度應小於300 ppb，一般認為超過400 ppb即會造成貧血等臨床症狀。雖然本研究觀察到貼敷硬膏劑後並未導致動物全血鉛濃度超過400 ppb，但以Paired t-test 統計分析，貼敷後之血中濃度皆呈現有意義的增加（P<0.05）。在實驗中觀察到此硬膏劑與皮膚之黏著非常牢固，對於需要重複貼敷的使用者而言，將可能在撕離貼布時傷及表皮角質層，而導致穿皮吸收量增加。

The traditional Chinese hard plasters have been widely used for millenniums. According to the traditional preparation process, yellow minium （Pb3O4） is often used to heat up with the sesame oil for a long period to form the hard plaster. The objective of this research is to explore the releasing behavior of lead and the possibility of lead poisoning due to transdermal absorption of lead from the hard plaster.No lead was detected in the dissolution media during 24 hours, which indicates the lead derived from yellow minium in the hard plaster must be incorporated firmly within the matrix of plaster. The average plasma lead concentration from New Zealand rabbits before applying the hard plasters was 85.48±24.72 ppb and that of one hour after applying was raised to 173.51± 36.81 ppb, then maintained at near levels thereafter until 30 hours.Although the lead levels in the blood samples post patching were below 300 ppb （recommended by ACGIH） and the systemic lead poisoning were not induced, they are statistically significant higher than those of pre-patching （paired t-test; p＜0.05）. It was also observed that the plaster was firmly adhered to the skin. The stratum corneum and epidermal layers of skin could be damaged by repeated tearing actions; thereby the penetrated amount of lead could be thus increased for patients who need repeated uses.