Novel reactive sorbents to sorb, immobilize, and transform malodorous molecules for palliative management of malignant fungating wounds

项目摘要/摘要 在美国，5%至14%的晚期癌症患者受到恶性真菌伤口(MFW)的影响。 可悲的是，与最惠国工人一起生活的人的平均预期寿命是6到12个月。恶臭是最多的 MFW的痛苦和虚弱的症状，导致呕吐，食欲不振和心理 痛苦，包括社交退缩、社交孤立、焦虑、孤独和抑郁。恶臭由以下原因引起 一种挥发性物质的混合物，包括酸、多胺和硫化物，如二甲基三硫化物 (DMTS)。目前用于管理异味的方法是：(A)减少引起异味的生物群落，(B) (C)吸收气味(例如，通过木炭、绿茶袋、猫砂等)。然而， 这些战略只能带来有限的成功，恶臭仍然是跨国公司最糟糕的方面。 晚期癌症患者护理的目标应该包括症状管理的姑息性方法。 以提高生活质量。为此，本项目将开发一种新的反应性吸着剂方法来吸附， 固定和/或转化由MFW产生的恶臭分子以改善气味 姑息治疗中的管理。这一新策略以前从未被报道过。我们会选择性地氧化 海藻酸盐(一种天然阴离子聚合物)，生成共价键合的醛基团，用于木炭涂层 形成多孔胺反应型吸附剂。在这种设计中，木炭将吸附多胺(例如，腐胺和 为减少其含量，藻酸盐上的羧酸基团将离子固定 胺通过酸/碱反应，醛基团将通过共价方式固定胺 无味亚胺结构的形成。此外，我们将使用壳聚糖，一种天然的阳离子聚合物，来涂布 过氧化苯甲酰(BPO)，一种治疗痤疮的温和氧化剂，在木炭上形成多孔酸/DMTS反应 吸着剂。木炭将吸附酸(例如，正丁酸、正戊酸和正己酸)和DMT，即壳聚糖 将通过酸碱反应与酸反应生成无味的盐，BPO将氧化DMT 将其转化为亚硫醚和硫代亚硫酸盐的衍生物，气味不那么难闻。这些加在一起 预计这些行动将显著提高气味管理水平。 本项目的具体目标是：(1)制备新型反应性吸着剂；(2)体外评价气味 新型反应型脱硫剂的控制性能，以及(3)评价新型反应型脱硫剂的性能 伤口状体外模型中的吸着剂。反应性吸着剂的一个独特特征是，它们不仅会吸附 恶臭分子可以降低分子含量，但它们也会与分子发生反应进行转化 它们变成了非挥发性的、无臭的(或带有不那么难闻的气味)分子。反应性吸着剂可以是 单独使用或与当前的气味管理策略一起使用，以进行全面的气味管理。因此，这项工作将 对临终癌症患者的姑息治疗有重大积极影响。

Project Summary/Abstract Malignant fungating wounds (MFWs) affect 5% to 14% of advanced cancer patients in the United States. Sadly, the average life expectancy for a person living with MFWs is six to twelve months. Malodor is the most distressing and debilitating symptom of MFWs, causing gagging, vomiting, loss of appetite, and psychological distress, including social withdrawal, social isolation, anxiety, loneliness, and depression. Malodor results from a cocktail of volatile agents that includes acids, polyamines, and sulfur compounds such as dimethyl trisulfide (DMTS). The current methods used to manage malodor are: (a) reducing bioburdens that cause odor, (b) masking the odor, and (c) absorbing the odor (e.g., via charcoal, green tea teabags, cat litter, etc.). However, these strategies offer only limited success and malodor continues to be the worst aspect of MFWs. The goals of advanced cancer patient care should include a palliative approach for symptom management to improve quality of life. To this end, this project will develop a novel reactive sorbent approach to sorb, immobilize, and/or transform malodorous molecules that are generated by MFWs to improve odor management in palliative care. This new strategy has never been reported before. We will selectively oxidize alginate (a natural anionic polymer) to generate covalently bonded aldehyde groups for charcoal coating to form porous amine-reactive sorbents. In this design, the charcoal will sorb polyamines (e.g., putrescine and cadaverine) to reduce their contents, the carboxylic acid groups on the alginate will ionically immobilize the amines through acid/base reactions, and the aldehyde groups will covalently immobilize the amines through the formation of odorless imine structures. Also, we will use chitosan, a natural cationic polymer, to coat benzoyl peroxide (BPO), a mild oxidizer for acne treatment, onto charcoal to form porous acid-/DMTS-reactive sorbents. The charcoal will sorb the acids (e.g., n-butyric, n-valeric, and n-caproic) and DMTS, the chitosan will react with the acids to form odorless salts through acid/base reaction, and the BPO will oxidize the DMTS to transform it into sulfoxide and thiosulfinate derivatives with a much less unpleasant odor. These combined actions are expected to improve the level of odor management significantly. The specific aims of this project are to: (1) fabricate new reactive sorbents, (2) evaluate in vitro the odor control performance of the new reactive sorbents, and (3) evaluate the performance of the new reactive sorbents in a wound-like in vitro model. A unique feature of the reactive sorbents is that they will not only sorb malodorous molecules to reduce the molecule content, but they also will react with the molecules to transform them into non-volatile, odorless (or with a much less unpleasant odor) molecules. The reactive sorbents can be used alone or with current odor-managing strategies for comprehensive odor management. Thus, this work will have a major positive impact on the palliative care of end-of-life cancer patients.