????皮膚。皮膚是一個(gè)堅(jiān)實(shí)致密的組織，用來保護(hù)人體免受外物傷害。雖然理論上藥物也能通過皮膚被人體攝取，但是像分子一樣大的胰島素需要電力刺激才能穿透皮膚。因此這種方法又貴又不實(shí)用。另外也有人嘗試通過用藥物舒張毛孔的方式來給藥，但是多年來毫無進(jìn)展。

????鼻粘膜。已經(jīng)有通過鼻粘膜成功使用胰島素的先例，但是對(duì)于日常使用來說，鼻粘膜還是太脆弱了。

????口腔內(nèi)壁。它也是一種有彈性的粘膜，而且也具有吸收能力（想一想咀嚼式的煙草）。把溶解狀態(tài)的胰島素通過像哮喘噴劑一樣的工具噴入口腔，已被證實(shí)是一種可以快速將胰島素吸收到血液中的方法。這也是一種很有希望的方法，目前正在美國(guó)和印度接受試驗(yàn)。

????肺。幾年前通過肺部吸收胰島素的方法被研究了出來，但這種方法的隱患是，長(zhǎng)期使用可能導(dǎo)致肺部損傷。美國(guó)藥監(jiān)局（FDA）雖然批準(zhǔn)了這種方法，但要求患者必須定期接受肺功能檢查。不過由于經(jīng)濟(jì)上并不實(shí)惠，再加上醫(yī)生很少使用這種療法，導(dǎo)致這種療法最終退出了市場(chǎng)。另一種類似產(chǎn)品已經(jīng)研究了一段時(shí)間了，而且不久即將接受FDA的審查。

????既然這些方法都不管用，為什么不把胰島素做成口服藥呢？這聽起來是個(gè)簡(jiǎn)單的答案，但實(shí)際上卻并不這么簡(jiǎn)單。首先，就像有的人有復(fù)發(fā)燒心癥狀，有的人有腸道易激綜合癥一樣，人的胃腸系統(tǒng)存在很大的個(gè)體差異。

????其次是“漢堡包綜合癥”。人吞下胰島素藥片后，它必須先經(jīng)過胃部的酸性環(huán)境的折磨，然后再在十二指腸中被消化酶“洗禮”一遍，然后再進(jìn)入腸道，最后才能進(jìn)入血液。另外胰島素還要經(jīng)過肝臟，有可能藥物還沒接觸到血液和人體組織，就已經(jīng)被肝臟破壞和分解了。

????許多藥企都嘗試過研制胰島素片劑，但最后都以失敗告終，但現(xiàn)在仍有一些制藥公司依然在鍥而不舍地研制最終能被血液吸收的口服胰島素。但我對(duì)他們的嘗試仍然持懷疑態(tài)度。

????我們?cè)倩貋砜纯次恼麻_頭提到的機(jī)器人藥片。它基本上就是一個(gè)聚合物膠囊，里面裝著很多用糖做的微型空心針。膠囊像普通藥物一樣吞入腹中后，可以安然進(jìn)入腸道。一旦進(jìn)入小腸，人體的酸性物質(zhì)就會(huì)溶解膠囊的外層，露出的微型氣球狀結(jié)構(gòu)會(huì)不斷膨脹，輕輕地將裝滿藥物的針頭推進(jìn)腸壁。

????這是一個(gè)非常有趣的概念，很可能發(fā)展成一個(gè)有效的給藥系統(tǒng)，但它離真正投入市場(chǎng)還有很遠(yuǎn)。它在胰島素上的應(yīng)用也仍然有待觀察。（財(cái)富中文網(wǎng)）

????本文作者吉拉爾德?伯恩斯坦博士是紐約市西奈山以色列醫(yī)療中心弗里德曼糖尿病研究所糖尿病管理項(xiàng)目的主任，曾任美國(guó)糖尿病協(xié)會(huì)主席。

????譯者：樸成奎

????

????Skin.The skin is a tough, dense tissue that protects our body by keeping foreign material out. Drugs can be delivered through the skin, but a large molecule like insulin needs a supplemental electrical force to pierce the skin. This is expensive and impractical. There have been attempts to use a patch with chemicals that open the pores, but over years it has not moved forward.

????Nasal membranes.Insulin has been successfully delivered through the nasal membranes, but they are too fragile for regular use.

????Lining of the mouth.This is a resilient membrane that also has absorptive capacity (think chewing tobacco). Insulin in solution has been sprayed into the mouth using an asthma-like inhaler that enables rapid absorption into the blood stream. This is a promising avenue that is undergoing tests in the U.S. and India.

????Lungs.A few years ago delivery to and through the lungs was developed, but there are and were concerns about long-term usage and lung damage. The FDA approved it but only with regular periodic pulmonary function tests. The financial impracticality and limited prescribing led the producer to take it off the market. Another product has been under study for some time and will be reviewed by the FDA.

????So if none of these really work, why not deliver insulin in a pill? Seems like a simple answer, but it's anything but. For one thing, as anyone with recurrent heartburn, irritable bowel and the like knows, no two days in the GI tract are the same.

????Then there's the hamburger syndrome. When insulin is swallowed, it must pass through the vicious acid environment of the stomach, then through the equally vicious pool of digestive enzymes in the duodenum, then finally onto and through the lining of the intestines before it enters the bloodstream. Insulin must also pass through the liver, where it may be destroyed or sequestered before reaching the general blood flow and the body's tissues.

????Many companies have tried and failed to package insulin in a pill, and several new systems designed to protect insulin from the body are under development. I remain skeptical.

????Which brings us back to the robotic device mentioned at the start, which is basically a capsule consisting of a polymer shell and a cargo of tiny, hollow needles made of sugar. Like a typical pill, the capsule is swallowed and makes its way through the GI tract. Once it reaches the small intestine, acids in the body dissolves the outer layer of the capsule, freeing a balloonlike structure that expands and gently pushes the drug-filled needles into the wall of the intestine.

????It is an interesting concept that could have legs as a drug-delivery system, but it's a long way from market. Its application to insulin also remains to be seen.

????Dr. Gerald Bernstein is director of the Diabetes Management Program at Friedman Diabetes Institute at the Mount Sinai Beth Israel Medical Center in New York City and past president of the American Diabetes Association.