Use of gastrointestinally administered porous enteron sorbent polymers to prevent or treat radiation induced mucositis, esophagitis, enteritis, colitis, and gastrointestinal acute radiation syndrome
Inventors
Ali, Humayra Begum • Golobish, Thomas D. • Capponi, Vincent J. • Chan, Phillip P. • Young, Wei Tai • SCHEIRER, Andrew Robert
Assignees
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Publication Number
US-10314859-B2
Publication Date
2019-06-11
Expiration Date
Abstract
Disclosed herein are compositions and methods for preventing or treating acute or chronic oral mucositis, esophagitis, enteritis, colitis, or gastrointestinal acute radiation syndrome (GI-ARS) caused by radiation exposure, using one or more enteron sorbent polymers administered gastrointestinally (e.g. orally, via feeding or gastric tube, via ostomy, or rectally).
Core Innovation
The invention relates to porous enteron sorbent polymer compositions and their gastrointestinal administration to a subject exposed to radiation, including radiation-induced gastrointestinal toxicities. The polymers are described as non-absorbable and highly porous, and are characterized by a pore structure with a total pore volume in a defined range of pore sizes and specified pore-volume ratios across pore diameter ranges. The pore structure and porosity are used to sequester intraluminal inflammatory mediators and bacterial toxins via pore capture/surface adsorption.
The enteron sorbent polymers are described as gamma-stable and radio-lucent to avoid interference with radiotherapy. In this context, the polymers are formed as cross-linked polymeric materials derived from polymerizable monomers and cross-linkers. The document further describes physical attributes of the polymeric material including bead/particle size ranges and biocompatible coatings/dispersants for the enteron sorbent polymers.
A proof-of-concept is described using a mouse partial-body irradiation model to evaluate gastrointestinal toxicity outcomes, including diarrhea severity/duration and survival-related metrics. The administered porous enteron sorbent polymer is reported to show trends toward improved survival metrics and reduced diarrhea compared to vehicle. The document additionally reports no observed residual beads in intestine/colon at days 7-9.
Claims Coverage
Two independent claims are provided: one method for administration after radiation exposure and one method for administration prior to radiation exposure. Both independent claims require gastrointestinal administration of one or more enteron sorbent polymers with specific pore-structure total pore volume and pore-volume ratio limitations across defined pore diameter ranges.
Radiation-exposed subject gastrointestinal administration with specified pore-volume distribution
A method comprising gastrointestinal administration of one or more enteron sorbent polymers to a subject that was exposed to radiation, wherein the enteron sorbent polymer has a pore structure with a total volume of pore sizes from 10 Å to 250,000 Å greater than 0.3 cc/g to 3.0 cc/g dry polymer, and wherein the ratio of pore volume between 10 Å to 250,000 Å in diameter to pore volume between 250 Å to 250,000 Å in diameter is smaller than 7:1 and the ratio of pore volume between 10 Å to 250,000 Å in diameter to pore volume between 50 Å to 250,000 Å in diameter is less than 2:1.
Radiation-preexposure gastrointestinal administration with specified pore-volume distribution
A method comprising gastrointestinal administration of one or more enteron sorbent polymers to a subject prior to exposure to radiation, wherein the enteron sorbent polymer has a pore structure with a total volume of pore sizes from 10 Å to 250,000 Å greater than 0.3 cc/g to 3.0 cc/g dry polymer, and wherein the ratio of pore volume between 10 Å to 250,000 Å in diameter to pore volume between 250 Å to 250,000 Å in diameter is smaller than 7:1 and the ratio of pore volume between 10 Å to 250,000 Å in diameter to pore volume between 50 Å to 250,000 Å in diameter is less than 2:1.
Across both independent claims, the claim coverage is centered on gastrointestinal administration of enteron sorbent polymers characterized by a defined pore structure: a total pore volume within a specified range for pore sizes 10 Å to 250,000 Å, and pore-volume ratio limits (<7:1 and <2:1) between defined pore diameter ranges of the cross-linked polymeric material.
Stated Advantages
Sequesters intraluminal inflammatory mediators and bacterial toxins via pore capture/surface adsorption.
Gamma-stable and radio-lucent to avoid interference with radiotherapy.
Reduces diarrhea severity/duration and shows trends toward improved survival metrics (time to 25% weight loss and higher day-8 survival proportion).
No observed residual beads in intestine/colon at days 7-9.
Documented Applications
Prevent or treat radiation-induced gastrointestinal toxicities, including oral mucositis, esophagitis, enteritis, colitis, and gastrointestinal acute radiation syndrome (GI-ARS).
A proof-of-concept evaluation in a mouse partial-body irradiation model for gastrointestinal toxicity outcomes including diarrhea severity/duration and survival-related metrics.
Use in a radiation context that includes radiotherapy, as reflected by the described avoidance of interference with radiotherapy.
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