肌膚保養的另一課題 -- 漫談經皮吸收的概念-2

看過上一篇文章的人一定會問，那些所謂的化學性滲透輔助劑CPE包括哪些東西呢？這篇文章主要在告訴大家一些相關資訊。

我們都知道，皮膚角質層細胞間的間隙是由雙層脂質的屏障(Barrier lipid bilayers)所構成，而所有的藥物或肌膚保養成分想要通過這個脂質屏障，需要考量的因素包括上篇文章所提到的像分子大小、溫溼度、皮膚損傷程度等等之外，另外一個重要因素就是所含親油基的程度。

其實在我以前的一些文章中都提到過，許多的合成酯類、酯醇類都可以當作所謂的助滲透劑，就是因為這類成份中的多屬親油性成份，但是在長期使用下，這些成分對肌膚的刺激性會因累積而增加，所以我非常反對使用過多合成酯類成份的肌膚保養品。但是，因為這類產品通常都有著優越的皮膚滲透性，在使用上的舒適性也不錯(因為親膚性佳的關係)，因此常常被一般消費者認為是優良的產品。然而請記住，像這些合成酯類的成份很容易通過皮膚，也因此它所造成肌膚危害的可能性當然也就比較大，尤其不同產品中的這些成份如果被相加(詳見部落格文章” 從產品設計的觀點(以EGF強效時空保濕復妍因子為例)談肌膚保養程序的簡化”)使用，那麼進入到皮膚內的濃度可能就會增加，長期使用後對皮膚的刺激性也會跟著加大。(在此再度提醒大家可以對照部落格文章” 肌膚保養成分的致痘性與刺激性”中的列表來確認成份的安全性)

這一篇研究報告是由以色列的Hebrew University of Jerusalem在2006年所發表的，在此將論文摘要提供給大家參考。

Adv Colloid Interface Sci. 2006 Nov 16;123-126:369-85.

Microemulsions as transdermal drug delivery vehicles.

(微乳化劑作為經皮輸藥媒介物)

Kogan A, Garti N.

Casali Institute of Applied Chemistry, The Institute of Chemistry, Givat Ram Campus, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.

Microemulsions are clear, stable, isotropic mixtures of oil, water, and surfactant, frequently in combination with a cosurfactant. Microemulsions have been intensively studied during the last decades by many scientists and technologists because of their great potential in many food and pharmaceutical applications. The use of microemulsions is advantageous not only due to the facile and low cost preparation, but also because of the improved bioavailability. The increased absorption of drugs in topical applications is attributed to enhancement of penetration through the skin by the carrier. Saturated and unsaturated fatty acids serving as an oil phase are frequently used as penetration enhancers. The most popular enhancer is oleic acid. Other permeation enhancers commonly used in transdermal formulations are isopropyl myristate, isopropyl palmitate, triacetin, isostearylic isostearate, R(+)-limonene and medium chain triglycerides. The most popular among the enhancing permeability surfactants are phospholipids that have been shown to enhance drug permeation in a different mode. l-alpha-phosphatidylcholine from egg yolk, l-alpha-phosphatidylcholine 60%, from soybean and dioleylphosphatidyl ethanolamine which are in a fluid state may diffuse into the stratum corneum and enhance dermal and transdermal drug penetration, while distearoylphosphatidyl choline which is in a gel-state has no such capability. Other very commonly used surfactants are Tween 20, Tween 80, Span 20, Azone, Plurol Isostearique and Plurol Oleique. As cosurfactants commonly serve short-chain alkanols such as ethanol and propylene glycol. Long-chain alcohols, especially 1-butanol, are known for their enhancing activity as well. Decanol was found to be an optimum enhancer among other saturated fatty alcohols that were examined (from octanol to myristyl alcohol). Many enhancers are concentration-dependent; therefore, optimal concentration for effective promotion should be determined. The delivery rate is dependent on the type of the drug, the structure and ingredients of the carrier, and on the character of the membrane in use. Each formulation should be examined very carefully, because every membrane alters the mechanism of penetration and can turn an enhancer to a retarder. Various potential mechanisms to enhance drug penetration through the skin include directly affecting the skin and modifying the formulation so the partition, diffusion, or solubility is altered. The combination of several enhancement techniques such as the use of iontophoresis with fatty acids leads to synergetic drug penetration and to decrease in skin toxicity. Selected studies of various microemulsions containing certain drugs including retinoic acid, 5-fluorouracil, triptolide, ascorbic acid, diclofenac, lidocaine, and prilocaine hydrochloride in transdermal formulations are presented in this review. In conclusion, microemulsions were found as an effective vehicle of the solubilization of certain drugs and as protecting medium for the entrapped of drugs from degradation, hydrolysis, and oxidation. It can also provide prolonged release of the drug and prevent irritation despite the toxicity of the drug. Yet, in spite of all the advantages the present formulations lack several key important characteristics such as cosmetic-permitted surfactants, free dilution in water capabilities, stability in the digestive tracts and sufficient solubilization capacity.

文章中的一些重點我將它敘述出來；[Microemulsions are clear, stable, isotropic mixtures of oil, water, and surfactant, frequently in combination with a cosurfactant.]微乳化劑是由油、水及界面活性劑所形成的清澈、穩定且等向的混合物，通常合併有多種聯合的界面活性劑。[The use of microemulsions is advantageous not only due to the facile and low cost preparation, but also because of the improved bioavailability. The increased absorption of drugs in topical applications is attributed to enhancement of penetration through the skin by the carrier.]使用微乳化劑的好處不只因為它容易控制及低的成本，還包括它可以改善生物學上的利用性，藉由這些微乳化劑對皮膚的加強滲透可以增加局部藥物的吸收。[Each formulation should be examined very carefully, because every membrane alters the mechanism of penetration and can turn an enhancer to a retarder.]每個微乳化劑的成分都必須經過小心的測試，因為每一個膜通透機轉的改變都可能將原本輔助滲透的作用轉變成阻礙的作用。[The combination of several enhancement techniques such as the use of iontophoresis with fatty acids leads to synergetic drug penetration and to decrease in skin toxicity.]合併其他加強滲透的方法像脂肪酸離子導入法可以協同加強藥物的滲透，並且減少皮膚所受的毒性。

介紹完本文後，相信大家對皮膚吸收的概念應該已經稍稍建立，我手上還有一些文章以後有機會再慢慢介紹給各位，但是在這裡，還是提一些許多文章中的建議給大家先參考一下。主要的建議在於，假如可能的話，合併使用經皮傳輸方式(例如簡單且濃度低的化學性滲透輔助劑加上超音波導入或離子導入)可以將皮膚吸收的比率大大增加，並且可以減少化學性皮膚滲透劑對肌膚的刺激性。

所以我的準則是，選擇含簡單成份組合但是有效調理成份豐富的產品，加上良好的超音波導入，就可以增加皮膚對產品的吸收度，達到良好的肌膚保養效果。

Dr. Hsieh 2007/1/12 於高雄市