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

新型反应性吸附剂可吸附、固定和转化恶臭分子，用于恶性真菌伤口的姑息治疗

• 批准号: 10544741
• 负责人: YUYU SUN
• 金额: $ 19.11万
• 依托单位: UNIVERSITY OF MASSACHUSETTS LOWELL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-30 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544741
• 关键词: Acids; Acne; Activated Charcoal; Advanced Malignant Neoplasm; Aerobic Bacteria; Affect; Aldehydes; Alginates; Amines; Anaerobic Bacteria; Anxiety; Benzoyl Peroxide; Biopolymers; Cadaverine; Cancer Patient; Carboxylic Acids; Caring; Charcoal; Chitosan; Distress; Environment; Equilibrium; Evaluation; Felis catus; Future; Gagging; General Practices; Goals; Green tea; Honey; Human; Imines; Immobilization; In Vitro; Iodine; Knowledge; Life Expectancy; Loneliness; Malignant - descriptor; Managed Care; Masks; Mental Depression; Methods; Metronidazole; Microbial Biofilms; Odors; Outcome; Palliative Care; Patient Care; Patients; Performance; Persons; Pilot Projects; Polyamines; Polymers; Population; Porosity; Putrescine; Quality of life; Reaction; Reporting; Salts; Side; Silver; Site; Social isolation; Sterile coverings; Structure; Sulfides; Sulfoxide; Sulfur Compounds; Symptoms; Technology; Temperature; Topical application; United States; Volatile Oils; Volatilization; Vomiting; Withdrawal; Work; Wound models; absorption; appetite loss; base; biomaterial compatibility; chemical reaction; chronic wound; covalent bond; design; disabling symptom; end of life; healing; improved; in vitro Model; new technology; novel; novel strategies; organic acid; palliative; preference; psychologic; psychological distress; social; success; sugar; symptom management; wound; wound dressing

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.

项目总结/摘要 在美国，恶性真菌伤口（MFW）影响5%至14%的晚期癌症患者。 不幸的是，与MFW一起生活的人的平均预期寿命是6至12个月。Malodor是世界上 MFW的令人痛苦和虚弱的症状，导致作呕，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。恶臭产生于 一种挥发性物质的混合物，包括酸、多胺和硫化合物，如二甲基三硫 （DMTS）。目前用于治理恶臭的方法是：（a）减少引起恶臭的二聚体，（B） 掩蔽气味，和（c）吸收气味（例如，通过木炭、绿色茶茶包、猫砂等）。然而，在这方面， 这些策略仅提供有限的成功，并且恶臭仍然是MFW最糟糕的方面。 晚期癌症患者护理的目标应包括症状管理的姑息方法 来提高生活质量。为此，本项目将开发一种新的反应吸附剂方法来吸附， 除臭，和/或转化由MFW产生的恶臭分子以改善气味 姑息治疗的管理。这种新策略以前从未报道过。我们会选择性地氧化 藻酸盐（天然阴离子聚合物）以产生用于木炭涂层的共价键合的醛基， 形成多孔胺反应性吸附剂。在这种设计中，木炭将吸附多胺（例如，腐胺和 尸胺）以减少它们的含量，藻酸盐上的羧酸基团将离子地取代藻酸盐。 胺通过酸/碱反应，并且醛基将共价地取代胺， 形成无味的亚胺结构。此外，我们将使用壳聚糖，一种天然的阳离子聚合物， 过氧化苯甲酰（BPO）是一种用于治疗痤疮的温和氧化剂，将其作用于木炭上，形成多孔酸/DMTS反应性物质 吸附剂。木炭将吸附酸（例如，正丁酸、正戊酸和正己酸）和DMTS（壳聚糖 通过酸碱反应与酸反应生成无味盐，BPO氧化DMTS 将其转化为具有更少令人不快的气味的亚砜和硫代亚磺酸酯衍生物。这些组合 预计这些行动将显著提高气味管理水平。 本课题的具体目标是：（1）制备新型反应性吸附剂，（2）对恶臭气体进行体外评价 控制新的反应吸附剂的性能，和（3）评价新的反应吸附剂的性能， 吸附剂在伤口样体外模型中。反应性吸附剂的一个独特特征是它们不仅可以吸附 恶臭分子减少了分子含量，但它们也会与分子发生反应而转化 将它们转化为非挥发性、无味（或具有更少令人不快的气味）的分子。反应性吸附剂可以是 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产生重大积极影响。