Stabilization of therapeutic microbes for inclusion in a liquid matrix for delivery to the intestines

稳定治疗微生物以包含在液体基质中以输送到肠道

• 批准号: 10603190
• 负责人: Aaron C Anselmo
• 金额: $ 29.59万
• 依托单位: VITAKEY, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603190
• 关键词: Acids; Adhesions; Alginates; Biopolymers; Carbohydrates; Carbon Dioxide; Cells; Chitosan; Clinical Research; Colloids; Colon; Complex; Critical Illness; Deglutition Disorders; Deposition; Desire for food; Dextrans; Diarrhea; Digestion; Drug Delivery Systems; Dryness; Eating; Elderly; Electrostatics; Emulsions; Encapsulated; Ensure; Enteral Feeding; Environment; Evaluation; Excipients; Fatty acid glycerol esters; Formulation; Gastrointestinal tract structure; Glycerol; Government; Growth; Health; Home; Hospitalization; Hospitals; Immune system; Immunity; Immunologics; Intestines; Inulin; Investigation; Lactobacillus casei rhamnosus; Length of Stay; Life; Liquid substance; Malignant Neoplasms; Marketing; Medical; Microbe; Micronutrients; Modernization; Nursing Homes; Nutrient; Nutritional; Oral; Oral Administration; Oxygen; Patients; Performance; Persons; Phase; Polysaccharides; Powder dose form; Probiotics; Procedures; Proteins; Recovery; Reporting; Risk; Sedimentation process; Sodium Chloride; Sterilization; Stomach; Stroke; Surface; System; Tannic Acid; Techniques; Technology; Temperature; Therapeutic; Time; Ventilator; Volatile Fatty Acids; Water; absorption; antimicrobial; beeswax; bile salts; cost; dietary supplements; disability; enteric pathogen; experience; gut colonization; gut health; gut microbiota; hazard; improved; intestinal barrier; liquid formulation; manufacture; microorganism; nutrient absorption; nutrition; pasteurization; prevent; probiotic therapy; reconstitution; sugar; technology platform

Project Summary/Abstract Enteral feeding (EF) is an essential medical procedure used to supply nutrients directly to the gastrointestinal (GI) tract of patients who are unable to eat independently. EF formula is often purchased as a ready-to-use liquid that contains carbohydrates, protein, fats, and micronutrients to ensure adequate nutritional benefit for the patient. The addition of therapeutic probiotics to EF formula has been shown to improve patient health and recovery, while reducing the cost burden to patients and hospitals. However, specific challenges remain which have prevented widespread use. These include: an instability of probiotics in nutrient rich, complex liquid mediums, including high fat, salt, or sugar liquids and biphasic systems such as emulsions and collo ids, a narrow list of compatible probiotics with marginal therapeutic benefit, a risk of cross-contamination during handling/reconstitution of powder probiotics, sedimentation/aggregation of probiotics, causing blockage of the feeding tube, inactivation of the probiotics by the acidic stomach environment, and a lack of proper adhesion and growth in the gastrointestinal tract. A platform drug delivery technology which encapsulates cells and stabilizes the compounds during storage and digestion while facilitating both mucoadhesion and direct growth on intestinal surfaces has previously been developed and will be optimized for use in liquid EF nutritional formula in this proposal. Lactobacillus rhamnosus HN001, a microbe reported to support gut health and the immune system, will be coated with the platform technology and evaluated for performance and shelf life stability in a complex liquid EF formula. Furthermore, multiple excipients with moisture barrier features will be explored in an effort to extend the liquid shelf life stability.

项目概要/摘要 肠内喂养 (EF) 是一种重要的医疗程序，用于直接向肠道提供营养 无法独立进食的胃肠道（GI）患者。 EF公式通常是 以即用型液体形式购买，含有碳水化合物、蛋白质、脂肪和微量营养素 以确保患者获得足够的营养。添加治疗性益生菌 EF 配方已被证明可以改善患者的健康和康复，同时降低成本 给患者和医院带来负担。然而，具体的挑战仍然存在，阻碍了 广泛使用。这些包括： 益生菌在营养丰富、复杂的液体培养基中不稳定，包括 高脂肪、盐或糖液体和双相系统，例如乳液和 胶体ID， 一小部分具有边际治疗效果的相容益生菌， 粉末益生菌处理/重构过程中存在交叉污染的风险， 益生菌沉淀/聚集，导致饲管堵塞， 酸性胃环境使益生菌失活，以及 胃肠道中缺乏适当的粘附和生长。 封装细胞并稳定化合物的平台药物递送技术 在储存和消化过程中，同时促进粘膜粘附和在肠道上的直接生长 表面先前已开发，并将针对液体 EF 营养品的使用进行优化 本提案中的公式。鼠李糖乳杆菌 HN001，一种据报道支持肠道的微生物 健康和免疫系统，将采用该平台技术并进行评估 复杂液体 EF 配方中的性能和保质期稳定性。此外，多个 将探索具有防潮特性的赋形剂，以延长液体保质期 生活稳定。