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N-乙酰基肉碱持续药物递送眼药水控制不老视力的迹象:眩光敏感性,白内障改善和视觉质量目前针对 50000 名患者人群的挑战性治疗方法。

N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population.

机构信息

Innovative Vision Products, Inc., County of New Castle, Delaware, USA.

出版信息

Clin Interv Aging. 2009;4:31-50. Epub 2009 May 14.

Abstract

BACKGROUND

Innovative Vision Products, Inc. (IVP)'s scientists developed the lubricant eye drops (Can-C) designed as 1% N-acetylcarnosine (NAC) prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C eye drops.

OBJECTIVE AND STUDY DESIGN

In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years.

SETTING

Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients' glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision.

PATIENTS OR OTHER PARTICIPANTS

The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C eye drops since December 2001.

INTERVENTION

Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the patients' compliance rate to self-administer NAC eye-drops.

MAIN OUTCOME MEASURE AND RESULTS

The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital-statistics and will be reported inherent in next N-acetylcarnosine ophthalmic drug studies.

CONCLUSION

The authors present evidence, about why only a certain kind of NAC is safe, and why only certain formulas designed by IVP for drug discovery are efficacious in the prevention and treatment of senile cataract for long-term use. Overall cumulated studies demonstrate that the designed by IVP new vision-saving drug NAC eye drops help the aging eye to recover by improving its clarity, glare sensitivity, color perception and overall vision.

摘要

背景

创新视觉产品公司(IVP)的科学家开发了这种润滑滴眼液(Can-C),它被设计为 1% N-乙酰基肉碱(NAC)前体药物,含有角膜吸收促进剂的黏附纤维素化合物,在持续药物输送系统中。只有天然 L-异构体形式的 NAC 原料是在 cGMP 设施中专门合成的,并用于制造 Can-C 滴眼液。

目的和研究设计

在目前的临床研究中,作者评估了 75 名有症状的年龄相关性单纯性白内障患者在 9 个月的眼部局部使用 NAC 润眼液或安慰剂后的视力,这些患者一眼的视力为 20/40 或更差(最佳矫正距离),并且两眼均未接受过白内障手术,也没有其他眼部异常,72 名非白内障受试者年龄在 54 岁至 78 岁之间。

地点

这些亚组患者曾抱怨畏光,希望滴用眼药水来快速缓解眼部不适,提高日常活动(包括驾驶和电脑工作)的视力。在使用 NAC 润眼液治疗 9 个月后,大多数患者的眩光评分在 Halometer DG 残疾眩光测试中得到改善或恢复正常。残疾眩光的改善伴随着视力的独立改善。此外,治疗前视力最差的患者在接受 N-乙酰基肉碱润眼液治疗 9 个月后,恢复一定更好的视力功能的可能性与治疗前视力较好的患者一样大。

患者或其他参与者

作者参考了自 2001 年 12 月以来产品销售给患者的电子记录,这些患者已经重新购买了 Can-C 滴眼液。

干预措施

基于对库存调整的分析,在继续购买行为计划中分析了各种参数,包括买家的证词。根据这些数据,研究人员根据患者对 NAC 眼药水的自我管理依从率进行了判断。

主要结果和测量

在控制年龄、性别和日常活动以及基于 5 万多名各种队列幸存者的重复购买行为报告的综合基础上,该眼科药物显示出了对年龄相关性白内障的非手术治疗潜力,已被证明对老年人具有较高的疗效和良好的耐受性,相对稳定的致盲和视力损害原因模式。研究人员考虑了 NAC 眼科药物预防和逆转白内障的机制,包括眼内释放的肉碱防止自由基诱导的专有晶状体抗氧化酶(超氧化物歧化酶)失活;预防碳水化合物和金属催化的抗坏血酸诱导的晶状体蛋白交联糖化反应;肉碱的转糖化特性,使其能够与糖化剂竞争,保护蛋白质(晶状体蛋白)免受修饰;对脂质过氧化物、醛和氧自由基具有通用的抗氧化和清除活性;激活晶状体中的蛋白酶体活性;晶状体蛋白的伴侣样解聚活性。失明发病率随年龄增长而增加,如白内障和青光眼,这些是目前样本中以及所有年龄组中最常见的失明原因,青光眼神经退行性变可以用开发的 NAC 自动诱导前体药物滴眼剂治疗,该滴眼剂配备了角膜吸收促进剂。在我们目前的生命统计数据总结中,发达国家常见的致盲疾病,如老年性黄斑变性、遗传性脉络膜视网膜营养不良、糖尿病性视网膜病变,代表性不足,在下一个 N-乙酰基肉碱眼科药物研究中,将报告这些疾病。

结论

作者提出了证据,解释了为什么只有特定种类的 NAC 是安全的,以及为什么只有 IVP 设计的特定配方在预防和治疗老年性白内障方面是有效的,可以长期使用。总的累积研究表明,由 IVP 设计的新的视觉保护药物 NAC 眼药水可以帮助老化的眼睛恢复清晰度、眩光敏感性、颜色感知和整体视力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d6c/2685223/cf7046f2dad4/cia-4-031f1.jpg

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