Ingestible in vivo-assembling drug release formulations and methods
AssigneesMassachusetts Institute of Technology, The Brigham and Women's Hospital, Inc.
InventorsCarlo Giovanni Traverso, Gary W. Liu, Matthew Pickett, Robert S. Langer
Life of this patent
Estimating the term…
Abstract
Systems and methods related to drug delivery are provided. In one arrangement, a fluid is administered to a subject in drinkable form, which can partially or fully solidify in the stomach or another area of the gastrointestinal tract to form a drug release article or composition.
Claims67
A composition, comprising:
- a first pharmaceutically acceptable fluid;
- and
- a second pharmaceutically acceptable fluid,
- wherein the first and second pharmaceutically acceptable fluids are configured to polymerize to form a double network hydrogel when mixed, and
- wherein the first and second pharmaceutically acceptable fluids are suitable for oral administration to a subject.
A method of forming a double network hydrogel at a location internal to a subject, comprising:
- orally administering a first pharmaceutically acceptable fluid and a second pharmaceutically acceptable fluid at a location internal of a subject.
A method of forming a double network hydrogel within a gastrointestinal tract of a subject, comprising:
- polymerizing at least a portion of first pharmaceutically acceptable fluid and at least a portion of second pharmaceutically acceptable fluid within the gastrointestinal tract the subject.
The composition, kit, or method as in any preceding claim, wherein the double network hydrogel comprises a first ionically-crosslinked polymer and a second covalently crosslinked polymer.
The composition, kit, or method as in any preceding claim, wherein the first ionically-crosslinked polymer comprises a polyanionic polymer.
The composition, kit, or method as in any preceding claim, wherein the polyanionic polymer comprises a backbone comprising carboxylic acids.
The composition, kit, or method as in any preceding claim, wherein the second covalently-crosslinked polymer comprises polyethylene glycol.
The composition, kit, or method as in any preceding claim, wherein the second covalently-crosslinked polymer comprises a maleimide and/or an azide.
The composition, kit, or method as in any preceding claim, wherein the double network hydrogel comprises alginates, karaya gum, gellan gum, and/or poly(ethylene glycols).
The composition, kit, or method as in any preceding claim, wherein the composition further comprises a therapeutic agent.
The composition, kit, or method as in any preceding claim, wherein the composition further comprises an excipient.
The composition, kit, or method as in any preceding claim, wherein the double network hydrogel is pharmaceutically acceptable.
The composition, kit, or method as in any preceding claim, wherein the first pharmaceutically acceptable fluid comprises calcium and a dithiol crosslinker.
The composition, kit, or method as in any preceding claim, wherein the second pharmaceutically acceptable fluid comprises alginate and a 4-arm poly(ethylene glycol)-maleimide.
The composition, kit, or method as in any preceding claim, wherein the dithiol crosslinker comprising poly(ethylene glycol)-dithiol and/or dimercaptosuccinic acid.
The composition, kit, or method as in any preceding claim, wherein each of the first ionically-crosslinked polymer and the second covalently crosslinked polymer polymerize in less than or equal to 30 minutes.
The composition, kit, or method as in any preceding claim, wherein each of the first ionically-crosslinked polymer and the second covalently crosslinked polymer polymerize in less than or equal to 10 minutes.
The composition, kit, or method as in any preceding claim, wherein each of the first ionically-crosslinked polymer and the second covalently crosslinked polymer polymerize in less than or equal to 5 minutes.
The composition, kit, or method as in any preceding claim, wherein the location internal to the subject is the stomach.
A composition comprising:
- a fluid drinkable by a subject, formulated to thicken to form a solid excipient when exposed to conditions similar or identical to those of at least one portion of the gastrointestinal tract of the subject.
A composition, comprising:
- a first configuration having a first, non-solid viscosity and formulated to thicken to a second configuration having a second viscosity greater than the first viscosity when exposed to conditions similar or identical to those of at least one portion of the gastrointestinal tract of a subject.
A composition as in claim B, wherein the first configuration is drinkable by a subject, and the second configuration is a spatially-segregated excipient locus internal of the gastrointestinal tract of the subject.
A method comprising:
- drinking a fluid;
- and
- allowing the fluid to at least partially harden internally of the gastrointestinal tract to form an excipient.
A method comprising:
- drinking a first fluid;
- drinking a second fluid;
- and
- allowing the first and second fluids to at least partially harden internally of the gastrointestinal tract to form an excipient.
A kit for delivery of a substance to a subject, comprising:
- a package containing a first composition and a second composition arranged so as not to be homogenously mixed prior to delivery to the subject, the package configured to deliver at least one of the first and second compositions to a subject as a fluid, wherein the first and second compositions are formulated such that when at least one composition is exposed to conditions similar or identical to those of at least one portion of the gastrointestinal tract of the subject, and at least a portion of the first composition is mixed with at least a portion of the second composition, a solid drug-release excipient is formed.
The composition, kit, or method as in any preceding claim, wherein the first and second compositions contain reactants configured to react internal to a subject and harden.
The composition, kit, or method as in any preceding claim, wherein the first and second compositions contain reactants configured to react internal to a gastrointestinal tract of a subject to form a hardened hydrogel.
The composition, kit, or method as in any preceding claim, wherein the fluid contains reactants that react internally to harden.
The composition, kit, or method as in any preceding claim, wherein the reactants are dissolved in fluid (distinguished from particulates in suspension)
The composition, kit, or method as in any preceding claim, wherein the fluid can be ingested in at least two portions separated in time or space, with potential overlap, or completely separate.
The composition, kit, or method as in any preceding claim, wherein the first fluid composition is a precursor and the second fluid/composition is a crosslinker.
The composition, kit, or method as in any preceding claim, wherein the first fluid/composition is a crosslinker and the second fluid/composition is a precursor.
The composition, kit, or method as in any preceding claim, wherein the method further comprises the ingesting the first pharmaceutically acceptable fluid and then ingesting the second pharmaceutically acceptable fluid.
The composition, kit, or method as in any preceding claim, wherein the second configuration is an excipient.
The composition, kit, or method as in any preceding claim, wherein the second configuration is a double network hydrogel.
The composition, kit, or method as in any preceding claim, wherein the first configuration is a fluid comprising a reactant and/or a crosslinker.
The composition, kit, or method as in any preceding claim, wherein a first viscosity is no more than 100,000 mPA s when measured at a temperature of 25 degrees C.
The composition, kit, or method as in any preceding claim, wherein a second viscosity is at least 1 mPA s when measured at a temperature of 25 degrees C.
The composition, kit, or method as in any preceding claim, further comprising an active agent in the first and/or second fluid.
A hydrogel that undergoes a transition from a liquid-to-solid state within the stomach and comprises two distinct polymer networks.
A kit comprising two solutions, wherein the two solutions, when mixed at a location internal to a subject, polymerize to a solid state comprising two distinct polymer networks, wherein a first polymer network comprises an ionic bond and a second polymer network comprises a covalent bond.
A method, comprising:
- ingesting a first fluid comprising a crosslinker;
- after ingesting the first fluid, ingesting a second fluid comprising a hydrogel;
- and
- forming discrete hydrogels having an average maximum dimension of less than or equal to 10 cm.
A method, comprising:
- ingesting a first fluid comprising a hydrogel precursor;
- after ingesting the first fluid, ingesting a second fluid comprising a crosslinker;
- and
- forming discrete hydrogels having an average maximum dimension of less than or equal to 10 cm.
The first fluid of any one of the preceding claims, further comprising a small molecule, a probiotic, a protein, an excipient, a multi-arm PEG functionalized with a reactive end-group, and/or divalent cation-crosslinked polymers such as alginate.
The second fluid of any one of the preceding claims, further comprising a small molecule, a probiotic, a protein, an excipient, a multi-arm PEG functionalized with a reactive end-group, and/or divalent cation-crosslinked polymers such as alginate.
The hydrogel precursor of any one of the preceding claims, wherein the multi-arm PEG comprises 2 arms, 4 arms, and/or 8 arms
The hydrogel solution of any one of the preceding claims, wherein the multi-arm PEG comprises a maleimide reactive end-group.
The hydrogels of any of the preceding claims, wherein a shape and/or size of the hydrogel is compatible with gastric clearance.
A kit, composition, or method as in any preceding claim, further comprising a delivery device comprising a first receptacle configured to contain the first fluid, a second receptacle configured to contain the second fluid, and at least one delivery pathway configured to deliver the first and second fluids to a location externally or internally of a subject.
A kit, composition, or method as in any preceding claim, wherein the composition or fluid is suitable for oral administration to the subject.
Dependencies are inferred from the claim text.