目的:N-[8-(2-羟基苯甲酰基)氨基]辛酸钠(SNAC)是广泛用于商业应用的众所周知的渗透增强剂。这项研究旨在通过将其转化为酚盐的新策略来扩大其性质。目的是研究SNAC酚盐的合成,特别是SNAC-胆碱(SNAC-CH),SNAC-钠(SNAC-Na),和SNAC-磷脂酰胆碱(SNAC-PC),并探讨其在提高司马鲁肽口服吸收方面的潜在应用。
方法:SNAC酚盐的合成通过1H-NMR确认,FTIR,和C的元素分析,H,N,进行体内测试以评估使用这些合成的SNAC酚盐口服递送司马鲁肽。测量药代动力学(PK)值以评估对药物吸收的影响。
结果:SNAC酚盐的合成(SNAC-CH,SNAC-Na,和SNAC-PC)在适当条件下成功实现,它们的结构使用分析技术如IR,NMR,和CHN元素分析。通过使用SNAC酚盐的口服药代动力学(PK)体内研究评估了它们的使用范式,这没有损害原始的SNACPK值。这表明该策略有望作为口服吸收的潜在新的有效增强剂。
结论:SNAC酚盐的利用为扩展渗透促进剂分子和性质的真实性提供了一种新颖且有前途的策略。合成酚盐代表了一种新的化学策略,可以为分子开发开辟新的途径。这种方法具有增强肽药物如斯马鲁肽的口服递送而不损害治疗功效的未来潜力。总的来说,它通过通过口服递送系统提供可注射肽的潜在替代方案,在该领域提供了重大进展。
OBJECTIVE: Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) is a well-known penetration enhancer widely used in commercial applications. This study aims to broaden its properties through a novel strategy of converting it into its phenolate salts. The objective is to investigate the synthesis of SNAC phenolate salts, specifically SNAC-choline (SNAC-CH), SNAC-sodium (SNAC-Na), and SNAC-phosphatidylcholine (SNAC-PC), and to explore their potential application in improving the oral absorption of semaglutide.
METHODS: The synthesis of SNAC phenolate salts was confirmed through 1H-NMR, FTIR, and an elemental analysis of C, H, N, and O. In vivo testing was conducted to assess the oral delivery of semaglutide using these synthesized SNAC phenolate salts. Pharmacokinetic (PK) values were measured to evaluate the impact on drug absorption.
RESULTS: The synthesis of SNAC phenolate salts (SNAC-CH, SNAC-Na, and SNAC-PC) was successfully achieved under appropriate conditions, and their structures were confirmed using analytical techniques such as IR, NMR, and CHN elemental analysis. The paradigm of their use was evaluated through an oral pharmacokinetic (PK) in vivo study using SNAC phenolate salts, which did not impair the original SNAC PK values. This suggests that this strategy holds promise as a potential new effective enhancer for oral absorption.
CONCLUSIONS: The utilization of SNAC phenolate salts presents a novel and promising strategy for extending the verity of penetration enhancers\' molecules and properties. Synthesizing phenolate salts represents a new chemical strategy that may open new avenues in molecular development. This approach holds future potential to enhance the oral delivery of peptide drugs like semaglutide without compromising therapeutic efficacy. Overall, it offers significant advancements in the field by providing a potential alternative to injectable peptides through oral delivery systems.