Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Tokitae LLC

Dean Liang Glettig

Robert Samuel Langer

Carlo Giovanni Traverso

Andrew Bellinger

Shiyi Zhang

Lowell L Wood, Jr

Philip Andrew Eckhoff

Angela DiCiccio

Stacy Mo

Tyler Grant

Mousa Jafari

Robert S Langer, Jr

Robert S Langer

Philip A Eckhoff

Lowell L Jr Wood

Ameya R Kirtane

Jiaqi Lin

Omar Abouzid

Angela Diciccio

Certain embodiments comprise administering a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance, and, optionally, a linker. In some such embodiments, the linker may be configured to degrade.

Residence structures and related methods

Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.g., ingestion of a solution that induces rapid dissolution/degradation). In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance (e.g., a therapeutic agent), and, optionally, a linker. In some such embodiments, the linker may be configured to degrade such that the residence structure breaks apart and is released from the location internally of the subject after a predetermined amount of time.

Enteric elastomers and related methods are generally provided. In some embodiments, the enteric elastomer is a polymer composite. Certain embodiments comprise a polymer composite in which hydrogen bonds within two carboxyl group-containing polymers cross-link the polymer networks into an elastic and pH-responsive polymer composite. Advantageously, this polymer composite has the capacity of being stable and elastic in an acidic environment such as that of the stomach but can be dissolved in a neutral pH environment such as that of the small and large intestines. In some embodiments, the polymer composites described herein comprise a mixture of two or more polymers with carboxyl functionality such that the two or more polymers form hydrogen bonds. In certain embodiments, the polymer composite has both enteric and elastic properties.

Enteric elastomers

Residence devices as well as their related methods of manufacture and use are generally provided. In some embodiments, a residence device includes a plurality of self-assembling structures that assemble in vivo to form an aggregate structure. Each structure of the plurality of structures includes a first side and a first attachment point that attaches to a second attachment point on another structure of the plurality of structures. The aggregate structure may be sized and shaped to maintain an in vivo position relative to an internal orifice of a subject. The attachment between the first and second attachment points may degrade after a period of time.

Self-assembled residence devices and related methods

Certain embodiments involve gastric residence structures which can be administered to a subject (e.g., a patient) in a configuration constrained by a retaining element, and configured to mediate a change in shape when unconstrained by the retaining element to assume a configuration in the stomach in which is retained and unable to pass through the gastric pyloric orifice of the subject under gastrointestinal physiological conditions. The residence structures can be loaded with an agent for release in the stomach.

Certain embodiments involve administering a residence structure to a subject (e.g., a patient) in a constrained configuration, then unconstraining the structure such that it is retained at a location internally of the subject for a period of time. The structure includes a loadable component that can carry an active substance for release internally of the subject.

Described are gastric residence structures that include an active substance. The gastric residence structures may include one or more arms that include a loadable polymeric component, an elastic polymeric component, and a separate linker component. The linker may connect the one or more arms with the elastic polymeric component. The gastric residence structures may be configured to be folded and physically constrained during administration and may be configured to assume an open retention shape upon removal of a constraint. The change between the folded shape and the open retention shape may be mediated by the elastic polymeric component that undergoes elastic deformation when the residence structure is in the folded shape and recoils when the gastric residence structure assumes the open retention shape.

Described are methods of making a gastric residence structure including an active substance. The methods may include forming one or more arms comprising a loadable polymeric component, wherein the loadable polymeric component includes one or more polymeric materials and at least one active substance. The methods may also include connecting the one or more arms to an elastic polymeric component using a separate linker component. The gastric residence structures may be configured to be folded and physically constrained during administration and may be configured to assume an open retention shape upon removal of a constraint. The change between the folded shape and the open retention shape may be mediated by the elastic polymeric component that undergoes elastic deformation when the residence structure is in the folded shape and recoils when the gastric residence structure assumes the open retention shape.

Growing community of inventors

Cambridge, MA, United States of America

Dean Liang Glettig