氟比洛芬酯脂微球制剂在止痛领域的研究概况

Research overview of flurbiprofen axetil injecction for analgesia

氟比洛芬酯脂微球注射液（商品名凯纷）是依据药物传递系统概念研究开发的以脂质微球为药物载体,包封氟比洛芬酯的新型非类固醇制剂,是目前惟一可静脉注射的非类固醇制剂。氟比洛芬酯是氟比洛芬脂化制备的前体药物,具有亲脂性。氟比洛芬酯脂微球注射液的特点主要有以下几方面：1）靶向性,使包裹的药物在病灶部位聚集增强药效;2）控制包裹药物的释放,使药效持续时间延长;3）易于跨膜转运,促进药物的吸收,进一步缩短起效时间;4）可静脉注射,避免了口服对消化道黏膜的损伤。作用机制主要是抑制花生四烯酸级联瀑布中环氧合酶的活性,从而抑制引起疼痛和炎症反应的前列腺素的合成,起到止痛作用。静脉注射后能迅速水解为活性物质氟比洛芬,其镇痛疗效强于阿司匹林,甚至超过了镇痛新;药物半衰期为5-8h,48h内排泄85%,主要以羟化合物和结合物的形式经肾脏排泄。氟比洛芬酯脂微球注射液除可单独应用外,还可与阿片类药物合用,在不加重阿片类药物不良反应的情况下,能增强镇痛效果且无中枢抑制作用。

Developed on the basis of the concept of drug delivery system, flurbiprofen axetil injection （trade name is Kaifen） is a new non-steroid preparation that enveloping flurbiprofen ester in the drug carrier of lipid microsphere. It is the only non-steroid preparation at present that can be administered intravenously. Flurbiprofen ester is the prodrug precipitated by flurbiprofen estrification which has lipophilicify. The main features of flurbiprofen axetil injection are as following： 1） Target tropism, which makes the packaged drug assemble in the focus of infection, and enhances drug action. 2） Controlled drug release, which can extend the drug action time. 3） Easy transmembrane transport, which can promote drug absorption to shorten the pre-effective time. 4） Intravenous administration, which can avoid damaging digestive tract membrane otherwise for oral use. Its mechanism of action is mainly to inhibit the activity of cyclooxygenase in the arachidonic acid cascade chute, which can inhibit the synthesis of prostaglandin that can cause pain and inflammatory reac tion. Then, it can take analgesic effect. By intravenous injection it can be hydrolyzed to active compound of flurbiprofen. Its analgesic action is higher than acenterine, even pentazocine. Its half life is 5-8 hours and 85% of it would be excreted through the kidney within 48 hours in the form of hydroxyl compound and conjugate. Except for the sole administration, flurbiprofen axetil injecction can be coadministered with opioid without adverse effect aggravation, which can enhance the analgesic effect with no central inhibitory action.