Development and clinical application of hydrogel formulations containing papain and urea for wound healing

Abstract Hydrogels are used for wound treatment, as they may contain one or more active components and protect the wound bed. Papain is one of the active substances that have been used with this purpose, alongside urea. In this paper, carboxypolymethylene hydrogels containing papain (2% and 10% concentrations) and urea (5% concentration) were produced. Physical-chemical stability was performed at 0, 7, 15 and 30 days at 2-8ºC, 25ºC and 40ºC, as well as the rheological aspects and proteolytic activity of papain by gel electrophoresis. Clinical efficacy of the formulations in patients with lower limb ulcers was also evaluated in a prospective, single-center, randomized, double-blind and comparative clinical trial. The results showed 7-day stability for the formulations under 25ºC, in addition to approximately 100% and 15% of protein activity for 10% and 2% papain hydrogel, respectively. The rheological profile was non-Newtonian for the 10% papain hydrogel tested. There were no significant differences regarding the mean time for healing of the lesions, although 10% papain presented a better approach to be used in all types of tissue present in the wound bed.摘要 水凝胶（Hydrogels）可应用于伤口治疗，因其可承载一种或多种活性成分并对创面床起到保护作用。木瓜蛋白酶（Papain）是已与尿素（Urea）一同用于该治疗用途的活性物质之一。本文制备了负载木瓜蛋白酶（浓度分别为2%与10%）及尿素（浓度为5%）的羧基聚亚甲基水凝胶（carboxypolymethylene hydrogels）。研究人员分别在2~8℃、25℃及40℃的储存条件下，于第0、7、15、30天对该制剂开展理化稳定性（Physical-chemical stability）测试，并通过凝胶电泳（gel electrophoresis）检测木瓜蛋白酶的流变学特性（rheological aspects）与蛋白水解活性（proteolytic activity）。此外，本研究通过一项前瞻性、单中心、随机双盲对照临床试验（prospective, single-center, randomized, double-blind and comparative clinical trial），评估了该制剂对下肢溃疡（lower limb ulcers）患者的临床疗效。结果显示，受试制剂在25℃条件下可稳定保存7天；浓度10%与2%的木瓜蛋白酶水凝胶的蛋白活性分别保留约100%与15%。受试的10%木瓜蛋白酶水凝胶的流变学特征表现为非牛顿型（non-Newtonian）流体。尽管10%浓度的木瓜蛋白酶对创面床内各类组织的适配性更佳，但两组患者的病灶平均愈合时间无统计学显著差异。