Effects of a New Enzymatic Debrider (SN514-066b) on Eschar Protein Digestion, Burn Wound Debridement, and Healthy Skin Irritation.

IF 5.8 3区 医学 Q1 DERMATOLOGY
Herbert B Slade, Barry T Reece, Nick D McCoy, Eric D Roche, Aleksa V Jovanovic, Lei Shi, Nasreen Jacobson
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Abstract

Objective: SN514 is a thermolysin-like enzyme under development as a debrider. Preclinical and non-clinical studies supported a first in human healthy volunteer study to predict the need for protection of periwound skin. Approach: Pharmacologic activity testing compared in vitro digestion of collagen, fibrin, and elastin with relevant enzymes. A Yorkshire pig model of burn injury was used to evaluate debridement over 10 days and effects on intact skin. A human 21-day cumulative irritation study using Webril patches taped to the backs of 38 healthy adult volunteers compared four enzyme concentrations (0.10%, 0.20%, 0.40%, and 0.80% w/w) with the hydrogel vehicle, saline (low irritant control), and 0.2% sodium lauryl sulfate (positive irritant control) using randomized placements and blinded evaluation. Results: SN514 showed excellent digestion of fibrin, elastin, and collagen in vitro. Burn wound studies in Yorkshire pigs showed efficient eschar debridement with minimal periwound erythema. Direct treatment on intact porcine skin for 5 days produced no to limited erythema. The preclinical findings of minimal irritation with SN514 were verified by a Phase 1 first-in-human 21-day cumulative skin irritation test. Irritation was observed to increase stepwise by concentration, confirming formulation accuracy. Each enzyme concentration was found to be "possibly mild in use" (Berger and Bowman method). No treatment emergent adverse events were observed during the study. Innovation: A fast-acting enzyme with a favorable irritation profile, prepared as a stable, ready to use hydrogel formulation, overcomes many recognized shortcomings of enzyme debriders. Conclusion: The overall findings support clinical dose range testing for tolerance and preliminary efficacy.

一种新型酶清创剂SN514-066b对痂蛋白消化、烧伤创面清创和健康皮肤刺激的影响
目的:SN514是一种正在开发的热溶素样酶。临床前和非临床研究支持第一项人类健康志愿者研究,以预测对创面周围皮肤的保护需求。方法:对胶原蛋白、纤维蛋白和弹性蛋白的体外消化与相关酶的药理活性进行比较。采用约克郡猪烧伤模型,评价10天内的清创及对完整皮肤的影响。一项为期21天的人体累积刺激研究使用Webril贴片贴在38名健康成年志愿者的背部,通过随机放置和盲法评估,将四种酶浓度(0.10%、0.20%、0.40%和0.80% w/w)与水凝胶载体、生理盐水(低刺激对照组)和0.2%十二烷基硫酸钠(阳性刺激对照组)进行比较。结果:SN514在体外对纤维蛋白、弹性蛋白和胶原蛋白有良好的消化能力。约克郡猪的烧伤研究显示有效的疮痂清创和最小的伤口周围红斑。在完整的猪皮肤上直接治疗5天,没有到有限的红斑。临床前研究发现,SN514对人体的刺激最小,并通过一项为期21天的人体累积皮肤刺激试验进行了验证。观察到刺激随着浓度的增加而逐渐增加,证实了配方的准确性。每一种酶的浓度都被发现“在使用中可能是温和的”(Berger和Bowman方法)。在研究期间未观察到治疗中出现的不良事件。创新:一种具有良好刺激特性的速效酶,作为一种稳定的、随时可用的水凝胶制剂,克服了许多公认的酶清毒剂的缺点。结论:本研究结果支持临床剂量范围耐受性试验和初步疗效试验。
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来源期刊
Advances in wound care
Advances in wound care Medicine-Emergency Medicine
CiteScore
12.10
自引率
4.10%
发文量
62
期刊介绍: Advances in Wound Care rapidly shares research from bench to bedside, with wound care applications for burns, major trauma, blast injuries, surgery, and diabetic ulcers. The Journal provides a critical, peer-reviewed forum for the field of tissue injury and repair, with an emphasis on acute and chronic wounds. Advances in Wound Care explores novel research approaches and practices to deliver the latest scientific discoveries and developments. Advances in Wound Care coverage includes: Skin bioengineering, Skin and tissue regeneration, Acute, chronic, and complex wounds, Dressings, Anti-scar strategies, Inflammation, Burns and healing, Biofilm, Oxygen and angiogenesis, Critical limb ischemia, Military wound care, New devices and technologies.
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