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-9931357-B2
Publication Date
2018-04-03
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 gastrointestinally administering one or more enteron sorbent polymers for treating acute or chronic oral mucositis, esophagitis, enteritis, colitis, or gastrointestinal acute radiation syndrome (GI-ARS) caused by radiation exposure. The enteron sorbent polymer is a non-absorbable, highly porous, cross-linked polymeric material with a defined pore-structure profile.
The pore structure includes 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. The pore-structure profile further constrains the relative pore-volume distributions in which 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.
The described mechanism is pore capture and surface adsorption of intra-luminal inflammatory mediators, followed by excretion of such mediators. The mediators include cytokines and bacterial toxins and endotoxins. By capturing and adsorbing intra-luminal inflammatory mediators and excreting them, the invention is described as reducing intestinal inflammation and gut permeability, and reducing bacterial/toxin translocation.
The polymer strategy is described in the context of radiation mitigation during radiotherapy, including gamma radiation stability and radiolucence. In documented examples, the approach is described as improving clinical outcomes such as weight loss and diarrhea severity and duration following partial-body irradiation.
Claims Coverage
Independent claim clm-00001 covers a method of treating radiation-induced acute or chronic oral mucositis, esophagitis, enteritis, colitis, or GI-ARS by gastrointestinal administration of an enteron sorbent polymer with a defined pore-volume profile. The claim contains multiple inventive features including the specific pore-volume ranges and pore-volume ratio constraints.
Gastrointestinal administration of enteron sorbent polymer for radiation-induced GI conditions
Gastrointestinal administration of one or more enteron sorbent polymers for treating acute or chronic oral mucositis, esophagitis, enteritis, colitis, or gastrointestinal acute radiation syndrome (GI-ARS) caused by radiation exposure.
Pore-volume range for total pore sizes (10 Å to 250,000 Å)
The enteron sorbent polymer has a pore structure with a total volume of pore sizes in the range of from 10 Å to 250,000 Å greater than 0.3 cc/g to 3.0 cc/g dry polymer.
Low pore-volume ratio for 10 Å–250,000 Å vs 250 Å–250,000 Å
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 of the cross-linked polymeric material is smaller than 7:1.
Low pore-volume ratio for 10 Å–250,000 Å vs 50 Å–250,000 Å
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 of the cross-linked polymeric material is less than 2:1.
Across the independent claim coverage, the method is defined by gastrointestinal administration of enteron sorbent polymers with constrained pore structure, specifically by total pore-volume range for 10 Å to 250,000 Å and ratio limits comparing pore volumes across specified diameter ranges. The claim scope is therefore tied to a defined porous, cross-linked polymer pore-volume distribution profile.
Stated Advantages
Reducing intestinal inflammation and gut permeability.
Reducing bacterial/toxin translocation and systemic inflammatory response syndrome (SIRS), including reduction of sepsis.
Reducing diarrhea severity and duration.
Improving clinical outcomes after partial-body irradiation, including reduced weight loss and increased time to 25% weight loss.
Documented Applications
Treating acute or chronic oral mucositis, esophagitis, enteritis, colitis, or gastrointestinal acute radiation syndrome (GI-ARS) caused by radiation exposure using gastrointestinal administration of enteron sorbent polymers.
Use in radiotherapy contexts described as benefiting from gamma radiation stability and radiolucence, including documented proof-of-concept after partial-body irradiation in C57BL/6 mice.
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