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N-乙酰基肉碱润眼液具有 L-肉碱在水相和脂膜环境中的全效抗氧化保护作用、醛清除作用和固有白内障的糖基化作用:数据库中超过 50500 例患者的新视力保护药物 N-乙酰基肉碱滴眼治疗的临床研究。

N-acetylcarnosine lubricant eyedrops possess all-in-one universal antioxidant protective effects of L-carnosine in aqueous and lipid membrane environments, aldehyde scavenging, and transglycation activities inherent to cataracts: a clinical study of the new vision-saving drug N-acetylcarnosine eyedrop therapy in a database population of over 50,500 patients.

机构信息

Innovative Vision Products, New Castle, Delaware, USA.

出版信息

Am J Ther. 2009 Nov-Dec;16(6):517-33. doi: 10.1097/MJT.0b013e318195e327.

Abstract

The antioxidant activity of L-carnosine (beta-alanyl-L-histidine, bioactivated in ocular tissues) versus N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine, ocular-targeted small dipeptide molecules) was studied in aqueous solution and in a lipid environment, employing liposomes as a model of lipid membranes. Reactive oxygen species (ROS) were generated by an iron/ascorbate promoter system for induction of lipid peroxidation (LPO). L-carnosine, which is stabilized from enzymatic hydrolysis, operates as a universal aldehyde and ROS scavenger in both aqueous and lipid environments and is effective at preventing ROS-induced damage to biomolecules. Second-generation carnosine analogs bearing the histidyl-hydrazide moiety were synthesized and tested versus L-carnosine for their ability to reverse the glycation process, also known as the Maillard reaction, and reverse the stable intermolecular cross-links, monitored in the glucose-ethylamine Schiff base model, ultimately resulting in the formation of the advanced glycation end products (AGEs) from nonenzymatic glycation, accumulating in numerous body tissues and fluids. The obtained data demonstrate the transglycation properties of the ophthalmically stabilized L-carnosine and L-carnosine histidyl-hydrazide derivatives tested and can be used to decrease or predict the occurrence of long-term complications of AGE formation and improve therapeutically the quality of vision and length of life for diabetes mellitus patients and survivors with early aging. Scientists at Innovative Vision Products, Inc. (IVP), developed lubricant eyedrops designed as a sustained-release 1% N-acetylcarnosine prodrug of L-carnosine. The eyedrops contain a mucoadhesive cellulose-based compound combined with corneal absorption promoters and glycerine in a drug-delivery system. Anti-aging therapeutics with the ophthalmic drug eyedrop formula including N-acetylcarnosine showed efficacy in the nonsurgical treatment of age-related cataracts for enrolled participants in the prospective, randomized, double-masked, placebo-controlled crossover clinical trial after controlling for age, gender, and daily activities. In a cohort in excess of 50,500 various patients seeking cutting-edge medical care, the N-acetylcarnosine topical eyedrops target therapy was demonstrated to have significant efficacy, safety, and good tolerability for the prevention and treatment of visual impairment in this older population with relatively stable patterns of causes for blindness and visual impairment. Overall, accumulated study data demonstrate that the IVP-designed new vision-saving drugs, including N-acetylcarnosine eyedrops, promote health vision and prevent vision disability from senile cataracts, primary open-angle glaucoma, age-related macular degeneration, diabetic retinopathy, and aging. N-acetylcarnosine eyedrop therapy is the crown jewel of the anti-aging medical movement and revolutionizes early detection, treatment, and rejuvenation of aging-related eye-disabling disorders. N-acetylcarnosine, as an innovative medical science tool and component of the home medicine and alternative medicine approaches, has the potential to alleviate visual impairment and its associated social, economic, and political woes for an aging population.

摘要

L-肉碱(β-丙氨酰-L-组氨酸,在眼部组织中生物激活)与 N-乙酰-L-肉碱(N-乙酰-β-丙氨酰-L-组氨酸,靶向眼部的小二肽分子)的抗氧化活性在水溶液和脂质环境中进行了研究,使用脂质体作为脂质膜的模型。通过铁/抗坏血酸促进剂系统产生活性氧(ROS),诱导脂质过氧化(LPO)。L-肉碱在酶解作用下得到稳定,在水相和油相环境中都作为一种通用的醛和 ROS 清除剂,能够有效预防 ROS 引起的生物分子损伤。合成了带有组氨酸酰肼部分的第二代肉碱类似物,并对其进行了测试,以研究它们逆转糖化过程(也称为美拉德反应)和逆转葡萄糖-乙胺希夫碱模型中稳定的分子间交联的能力,最终导致非酶糖化形成晚期糖基化终产物(AGEs),在许多身体组织和体液中积累。所得数据表明,所测试的眼内稳定的 L-肉碱和 L-肉碱组氨酸酰肼衍生物具有转糖基化特性,可用于减少或预测 AGE 形成的长期并发症的发生,并改善糖尿病患者和早期衰老幸存者的视力和寿命质量。创新视觉产品公司(IVP)的科学家开发了一种设计用作 L-肉碱的 1% N-乙酰-L-肉碱前药的润滑滴眼剂。该滴眼剂含有一种粘弹性纤维素基化合物,与角膜吸收促进剂和甘油结合在药物输送系统中。含有眼科药物滴眼剂配方的抗衰老疗法,包括 N-乙酰-L-肉碱,在年龄、性别和日常活动因素得到控制的情况下,在一项针对年龄相关性白内障的前瞻性、随机、双盲、安慰剂对照交叉临床试验中,对入组参与者显示出治疗效果。在超过 50500 名寻求前沿医疗护理的各种患者队列中,证明 N-乙酰-L-肉碱局部滴眼剂靶向疗法具有显著的疗效、安全性和良好的耐受性,可预防和治疗该老年人群的视力障碍,该人群的失明和视力障碍的原因模式相对稳定。总体而言,累积的研究数据表明,IVP 设计的新型保眼药物,包括 N-乙酰-L-肉碱滴眼剂,可促进健康视力,并预防老年性白内障、原发性开角型青光眼、年龄相关性黄斑变性、糖尿病性视网膜病变和衰老引起的视力障碍。N-乙酰-L-肉碱滴眼剂治疗是抗衰老医学运动的皇冠上的明珠,它彻底改变了与衰老相关的致盲性眼病的早期发现、治疗和年轻化。N-乙酰-L-肉碱作为一种创新的医学科学工具和家庭医学和替代医学方法的组成部分,具有减轻视觉障碍及其相关的社会、经济和政治困境的潜力,这些问题困扰着老龄化人口。

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