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6-姜烯酚自微乳给药系统对模型大鼠的降血尿酸作用:制剂设计与评价。

Anti-hyperuricemic property of 6-shogaol via self-micro emulsifying drug delivery system in model rats: formulation design, and evaluation.

机构信息

a Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering , Jiangsu University , Zhenjiang , China.

b Department of Biochemistry and Biotechnology, College of Science , KwameNkrumah University of Science and Technology , Kumasi , Ghana.

出版信息

Drug Dev Ind Pharm. 2019 Aug;45(8):1265-1276. doi: 10.1080/03639045.2019.1594885. Epub 2019 May 17.

DOI:10.1080/03639045.2019.1594885
PMID:30990749
Abstract

The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger ( Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00 ± 0.26 nm and 0.18 ± 0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.

摘要

高尿酸血症在全球范围内的患病率相对较高,有大量患者正在遭受其并发症的困扰。6-姜酚,一种从生姜(Roscoe)根部提取的烷基酚化合物,已被证明具有多种药理活性。然而,其较差的水溶性通常导致其生物利用度较低,进一步的临床应用将大大折扣。本研究旨在通过制备 6-姜酚负载自微乳给药系统(SMEDDS)来改善其口服低水溶性和生物利用度,并增强 6-姜酚的降尿酸活性。SMEDDS 是通过在两个系统成分(即 18.62%W/W 乙基油酸(油相)和吐温 80(表面活性剂)与聚乙二醇 400(助表面活性剂)的比例(1.73:1,W/W)的中心复合设计建立的。基于二次模型,设计空间的导航可以生成具有各自平均粒径、多分散性和 20.00±0.26nm 和 0.18±0.02 的球形和均匀液滴。与游离 6-姜酚相比,6-姜酚-SMEDDS 显示出显著增加的累积释放,更重要的是,药物的相对口服生物利用度增加了 571.18%。6-姜酚-SMEDDS 在肝脏中的主要积累表明该药物具有肝靶向潜力。在高尿酸血症大鼠中口服给予 6-姜酚-SMEDDS 也显著降低了尿酸水平和黄嘌呤氧化酶活性。组织学研究证实,配方组确实可以为肾脏提供比游离药物组更好的保护。总之,这些发现表明 SMEDDS 在增强 6-姜酚的口服递送和治疗效果方面具有很大的潜力。

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