Innovative Vision Products, Inc., 3511 Silverside Road, Suite 105, County of New Castle, Delaware 19810, USA.
Drug Test Anal. 2012 Jun;4(6):468-85. doi: 10.1002/dta.265. Epub 2011 Mar 18.
A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of the study document that the therapeutic benefit in clinical trials is associated with the bioactivation universal antioxidant and transglycating properties of N-acetylcarnosine acting as the ophthalmic prodrug of L-carnosine, and depends on the nature of the specific drug delivery lubricant eye-drop formulation applied as the topical solution. The research highlights findings in N-acetylcarnosine prodrug activation, transport mechanisms, drug-to-drug interactions, and formulations in order to unlock the optimization of complicated ocular pharmacology of N-acetylcarnosine. Patented N-acetylcarnosine lubricant eye-drop formula was marketed as numerous human biological brands reaching important distribution networks on over 550 000 bottles sold. Nature Does Nothing Uselessly. -Aristotle
相当多的人对 N-乙酰基肉碱眼部药物设计用于眼部健康感兴趣，这是基于通过代谢酶激活来改善眼部药物输送的临床策略。本文描述了 N-乙酰基肉碱穿过角膜到达房水的过程中的人眼生物学方面，以及二肽水解酶。通过增加生物激活的代谢物肉碱的眼内生物利用度，为眼部药物输送提供了新的途径，这成为确保药物在黏附性前角膜区域的长时间保留和促进天然二肽通过角膜促进剂穿透角膜的综合发展的重要部分。本文考虑了用于肽类药物设计、合成、纯化和生物学分析的综合技术列表：液相色谱 (LC)、高效液相色谱 (HPLC)、(1)H 和 (13)C 核磁共振 (NMR)、电喷雾电离 (ESI) 质谱和分光光度法。研究了靶向治疗的分子的抗氧化活性在水溶液和脂质膜环境中的情况。通过将糖或醛部分从席夫碱转移到组氨酸酰肼化合物或醛清除剂 L-肉碱中，开发了一种去糖基化治疗系统。临床研究包括检眼镜、视力 (VA)、眼压计眩光测试、裂隙像和反射照明摄影。N-乙酰基肉碱 1%润滑剂滴眼剂被认为是一种自动诱导前药和天然眼部氧化还原状态平衡疗法，对涉及眼组织连续氧化损伤的严重眼病（白内障、原发性开角型青光眼、年龄相关性黄斑变性）和威胁视力的糖基化过程（糖尿病性视网膜病变和随之而来的视力障碍）的预防和治疗具有重要意义，这些过程对公共健康很重要。研究结果表明，临床试验中的治疗益处与 N-乙酰基肉碱的生物激活通用抗氧化剂和转糖基化特性有关，该特性作为 L-肉碱的眼科前药，并且取决于所应用的特定药物输送润滑剂滴眼剂配方的性质。研究重点是 N-乙酰基肉碱前药激活、转运机制、药物相互作用和制剂方面的发现，以释放 N-乙酰基肉碱复杂的眼部药理学的优化。已获得专利的 N-乙酰基肉碱润滑剂滴眼剂配方已作为许多人体生物学品牌上市，通过超过 550,000 瓶的销售量进入了重要的分销网络。大自然不会做无用的事。-亚里士多德
