Study on the Percutaneous Absorption Behavior of Compound Nanxing Zhitong Plaster Based on Different Skin Model
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摘要:
目的 制备复合磷脂脂质体人工皮肤膜(Composite phospholipid liposome-based artificial skin membrane, CPLASM)以评价复方南星止痛膏(Compound Nanxing Zhitong Plaster, CNZP)的透皮吸收行为。 方法 建立同时测定CNZP中5种活性成分(桂皮醛、丹皮酚、丁香酚、水杨酸甲酯和欧前胡素)的HPLC分析方法。制备CPLASM并与市售人工皮肤膜Strat-MTM、真实皮肤(猪耳皮和大鼠皮)一起用于考察CNZP体外透皮吸收行为, 通过透皮吸收参数分析, 比较不同人工皮肤膜与真实皮肤之间的相似度。 结果 HPLC法能同时测定CNZP中5种活性成分的含量。在活性成分中, 桂皮醛和丁香酚的透皮吸收能力最强。CPLASM、Strat-MTM与猪耳皮测定的5种活性成分表观渗透系数相关系数分别为0.965 8和0.943 3, 与大鼠皮测定的5种活性成分表观渗透系数相关系数分别为0.949 3和0.946 0。 结论 应用CPLASM能够有效表征CNZP中活性成分体外透皮吸收行为。 -
关键词:
- 复方南星止痛膏 /
- 透皮吸收 /
- 复合磷脂脂质体人工皮肤膜 /
- 猪耳皮
Abstract:OBJECTIVE To evaluate the biopharmaceutical properties of five active ingredients in Compound Nanxing Zhitong Plaster (CNZP)by composite phospholipid liposome-based artificial skin membrane (CPLASM). METHODS The HPLC analysis method was established to simultaneously determine five active ingredients (cinnamic aldehyde, paeonol, eugenol, methyl salicylate and imperatorin) in CNZP. CPLASM were prepared and used to measure the in vitro transdermal absorption parameters of the five active ingredients from CNZP in comparison with Strat-MTM, the marketed artificial skin membrane. The obtained parameters were further compared with those obtained by rat skin and porcine ear skin. RESULTS The five active components can be simultaneously measured by HPLC analysis. Among the five active ingredients, eugenol and methyl salicylate were found to possess the best permeability. The apparent permeability coefficient correlation between CPLASM and porcine ear skin was determined to be 0.965 8 and 0.943 3 while that between Strat-MTM and porcine ear skin was found to be 0.949 3 and 0.946 0, respectively. CONCLUSION CPLASM can be used to evaluate the permeation behavior of plasters of Chinese medicine such as CNZP. -
图 1 CNZP 5种活性成分的HPLC色谱图
注：A.混合对照品溶液; B.CNZP供试品溶液; C.透皮接收液 1.桂皮醛; 2.丹皮酚; 3.丁香酚; 4.水杨酸甲酯; 5.欧前胡素
Figure 1. HPLC chromatogram of five active ingredients from CNZP
图 2 CNZP 5种活性成分体外透皮行为(x±s, n=6)
Figure 2. In vitro transdermal behavior of five active ingredients from CNZP (x±s, n=6)
图 3 CNZP 5种活性成分在不同皮肤模型中的透皮参数相关性
Figure 3. Percutaneous parameter correlation of five active ingredients from CNZP among different skin models
表 1 梯度洗脱条件
Table 1. Gradient elution conditions
时间/min 乙腈/% 超纯水/% 0~8 20~40 80~60 8~20 40~50 60~50 20~25 50~60 50~40 25~27 60~80 40~20 
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表 2 CNZP中5种活性成分采用Strat-MTM、猪耳皮、CPLASM及大鼠皮评价得到的透皮参数(x±s, n=6)
Table 2. The transdermal parameters of five active ingredients from CNZP obtained by Strat-MTM, porcine ear skin, CPLASM and rat skin (x±s, n=6)
成分 Jss/(μg·cm-2·h-1) Papp/(cm·s·10-7) 猪耳皮 大鼠皮 Strat-MTM CPLASM 猪耳皮 大鼠皮 Strat-MTM CPLASM 桂皮醛 0.52±0.01 1.06±0.07 0.84±0.09 0.95±0.10 43.19±1.27 86.83±6.25 68.63±7.69 77.65±8.42 丹皮酚 0.31±0.01 0.69±0.08 0.52±0.02 0.62±0.02 11.37±0.62 24.60±2.93 18.67±0.93 22.20±0.96 丁香酚 5.17±0.24 13.50±0.90 10.90±0.82 10.50±0.26 23.02±1.07 60.35±4.05 48.53±3.67 46.92±1.17 水杨酸甲酯 2.25±0.19 4.10±0.76 12.10±0.80 12.90±0.34 3.86±0.33 7.04±1.32 20.87±1.37 22.15±0.6 欧前胡素 0.03±0.00 0.10±0.01 0.00±0.00 0.02±0.01 4.90±0.47 13.07±2.29 1.19±0.75 3.54±1.97
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