肌膚保養的另一課題 -- 漫談經皮吸收的概念-1 @

肌膚保養的另一課題 -- 漫談經皮吸收的概念-1

許多的消費群眾在採購肌膚保養品的時候，最重視的焦點都放在產品的成分與功效上，但是對於保養品能否良好的滲透進皮膚裡頭往往並不是那麼注意，其實，日常肌膚保養品的效果除了取決於產品的組成分以外，還有一個重要命題，就是經皮滲透的比率，換成肌膚保養上常見的說法，就是成分被皮膚吸收的程度。

經常做肌膚保養的人都知道，皮膚的角質層是一個很緻密的組織，除了能阻擋外界環境對皮膚的傷害(包括一些不良化學成分的刺激與損傷)，達到保護皮膚的功能外，它還有防止皮膚水份散失的功能。但是，相對而言，想要讓保養品能夠滲透過皮膚的角質層以增加產品的皮膚吸收率，其實並不容易，這時候除了成份本身的分子大小以外，其他像成分的溶解度、環境的溫度、溼度、皮膚的狀況(皮膚是否有相當的損傷)等因素都會影響產品對皮膚的滲透性。

有人一定會問到，到底多大的分子是比較容易滲透過皮膚角質層？根據一些研究指出分子量在500 Dalton以下的分子是很容易通過角質層間隙的(這就是所謂的500 Dalton Rule)。那麼分子量大於500的成份是不是就無法滲入皮膚組織呢？我的答案是“這樣的分子大小的確比較不容易通過角質層”，但是並不是不能被皮膚所吸收利用，因為影響分子通過角質層的因素如上所述有很多，以皮膚損傷來說就是一個很常見的因素，因為許多的皮膚損傷往往是不自覺的(最明顯的例子就是陽光紫外線的傷害與物理性去角質產品的皮膚損傷)，而這些皮膚損傷就會造成角質層的間隙擴大，成份分子的滲入性就會增加。另外，像一些皮膚附屬器官(毛孔、汗腺等)也能提供較大分子進入皮膚組織的通透管道，即使通過的量不是很多。

在過去數十年來，關於經皮傳輸的研究相當的蓬勃，主要發展的目的是希望能提供更安全有效的藥物給予方式，就這樣在保養品的吸收研究上，也跟著得到一些啟發與成果，例如超音波導入與離子導入的概念，都是源發於經皮輸藥的研究上。在進入更深入的說明以前，我還是先提供我看過的一些論文資料的摘要給大家，當然，如果諸位對這方面有興趣的話，相當歡迎提出來一同討論。

Curr Med Chem. 2000 Jun;7(6):593-608.

Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery.

(經皮輸藥方面化學性滲透輔助劑的結構與活性關係)

Kanikkannan N, Kandimalla K, Lamba SS, Singh M.

College of Pharmacy, Florida A & M University , Tallahassee , FL 32307 , USA .

Transdermal drug delivery (TDD) is the administration of therapeutic agents through intact skin for systemic effect. TDD offers several advantages over the conventional dosage forms such as tablets, capsules and injections. Currently there are about eight drugs marketed as transdermal patches. Examples of such products include nitroglycerin (angina pectoris), clonidine (hypertension), scopolamine (motion sickness), nicotine (smoking cessation), fentanil (pain) and estradiol (estrogen deficiency). Since skin is an excellent barrier for drug transport, only potent drugs with appropriate physicochemical properties (low molecular weight, adequate solubility in aqueous and non-aqueous solvents, etc) are suitable candidates for transdermal delivery. Penetration enhancement technology is a challenging development that would increase significantly the number of drugs available for transdermal administration. The permeation of drugs through skin can be enhanced by physical methods such as iontophoresis (application of low level electric current) and phonophoresis (use of ultra sound energy) and by chemical penetration enhancers (CPE). In this review, we have discussed about the CPE which have been investigated for TDD. CPE are compounds that enhance the permeation of drugs across the skin. The CPE increase skin permeability by reversibly altering the physicochemical nature of the stratum corneum, the outer most layer of skin, to reduce its diffusional resistance. These compounds increase skin permeability also by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle. This review compiles the various CPE used for the enhancement of TDD, the mechanism of action of different chemical enhancers and the structure-activity relationship of selected and extensively studied enhancers such as fatty acids, fatty alcohols and terpenes. Based on the chemical structure of penetration enhancers (such as chain length, polarity, level of unsaturation and presence of some special groups such as ketones), the interaction between the stratum corneum and penetration enhancers may vary which will result in significant differences in penetration enhancement. Our review also discusses the various factors to be considered in the selection of an appropriate penetration enhancer for the development of transdermal delivery systems.

這一篇文章是2000年美國佛羅里達A & M大學的研究報告，文章中指出[The permeation of drugs through skin can be enhanced by physical methods such as iontophoresis (application of low level electric current) and phonophoresis (use of ultra sound energy) and by chemical penetration enhancers (CPE)].(藥物經由皮膚的滲透性可以藉由物理的方法像離子導入法及超音波導入法，以及化學性滲透輔助劑CPE來加強。[CPE are compounds that enhance the permeation of drugs across the skin. The CPE increase skin permeability by reversibly altering the physicochemical nature of the stratum corneum, the outer most layer of skin, to reduce its diffusional resistance. These compounds increase skin permeability also by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle.](化學性滲透輔助劑是一群可以幫助藥物通過皮膚的組成物，這些化學性滲透輔助劑藉由可逆性的改變角質層的物理化學性質來增加皮膚的通透性，降低滲透阻力。另外，這興化學性滲透輔助劑還可以藉由增加藥物進入皮膚的分離係數以及增加藥物在這些媒介物中的熱動力活性來增加皮膚的通透性。