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.

项目概要/摘要 在美国，恶性蕈状伤口 (MFW) 影响着 5% 至 14% 的晚期癌症患者。 遗憾的是，家庭佣工的平均预期寿命为六到十二个月。恶臭是最严重的 MFW 的令人痛苦和虚弱的症状，导致作呕、呕吐、食欲不振和心理障碍 痛苦，包括社交退缩、社交孤立、焦虑、孤独和抑郁。恶臭的结果来自 挥发性物质的混合物，包括酸、多胺和硫化合物，例如二甲基三硫醚 （DMTS）。目前用于控制恶臭的方法是：(a) 减少引起异味的生物负载，(b) 掩盖气味，以及 (c) 吸收气味（例如通过木炭、绿茶袋泡茶、猫砂等）。然而， 这些策略只取得了有限的成功，而且恶臭仍然是 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 提高生活质量。为此，该项目将开发一种新型反应吸附剂方法来吸附， 固定和/或转化 MFW 产生的恶臭分子以改善气味 姑息治疗的管理。这一新策略此前从未被报道过。我们将选择性氧化 海藻酸盐（一种天然阴离子聚合物）产生共价键合的醛基，用于木炭涂层 形成多孔胺反应性吸附剂。在该设计中，木炭将吸附多胺（例如腐胺和 尸胺）以减少其含量，藻酸盐上的羧酸基团将离子固定 胺通过酸/碱反应，醛基通过共价键固定胺 形成无味的亚胺结构。此外，我们将使用壳聚糖（一种天然阳离子聚合物）来涂覆 过氧化苯甲酰 (BPO) 是一种用于治疗痤疮的温和氧化剂，在木炭上形成多孔酸/DMTS 反应性 吸附剂。木炭会吸附酸（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 会氧化 DMTS 将其转化为亚砜和硫代亚磺酸盐衍生物，其难闻气味要少得多。这些结合起来 预计行动将显着提高气味管理水平。 该项目的具体目标是：（1）制造新型反应性吸附剂，（2）体外评估气味 新型反应吸附剂的控制性能，以及（3）评估新型反应吸附剂的性能 类似伤口的体外模型中的吸附剂。反应性吸附剂的一个独特之处在于它们不仅会吸附 恶臭分子会降低分子含量，但也会与分子发生反应转化 将它们转化为非挥发性、无味（或气味少得多）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。