Macromolecular prodrugs for light-emitting diodes and uses thereof
Inventors
Kohane, Daniel S. • Zhang, Wei
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12427196-B2
Publication Date
2025-09-30
Expiration Date
Abstract
Provided herein are compositions comprising macromolecular photocleavable prodrug compounds of Formula (I), and pharmaceutically acceptable salts, co-crystals, tautomers, stereoisomers, solvates, hydrates, polymorphs, and isotopically enriched derivatives thereof. Also provided are methods, uses, pharmaceutical compositions, and kits involving the inventive compounds or compositions for treating and/or preventing a disease and/or condition (e.g., inflammatory disease, infectious disease, pain) in a subject, optionally comprising illumination of the compound, composition, or pharmaceutical composition with light of an absorption wavelength sufficient to cleave the bonds between each instance of L and each instance of X upon illumination with the light (e.g., light between approximately 200 nm to 500 nm).
Core Innovation
The invention relates to a composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or isotopically enriched derivative thereof. The compound includes anesthetic moieties X, each instance of L being independently a photocleavable linker, and at least one instance of L comprising coumarin, o-nitrobenzyl, benzoin, 7-nitroindoline, or p-hydroxyphenacyl. The composition further includes a block copolymer P comprising at least one polyether.
The disclosed compounds are macromolecular photocleavable prodrug compositions for on-demand drug release. Cleavage of the L–X bond is triggered by illumination with light having an absorption wavelength approximately 200 nm to 500 nm, and the light-triggered cleavage releases active anesthetic/local anesthetic. The polymer-linked scaffold is described in forms including P-(L-X)n and X-L-P-L-X.
The composition is implemented using polymer scaffolds that include hydrophilic/amphiphilic block copolymers such as poloxamers, including poloxamer P407. The disclosure further frames the approach as combining gelation and injectability with light-controlled activation, producing inactivity without irradiation and repeatable triggering, while reducing unwanted initial nerve block and basal drug release.
Claims Coverage
The independent claim scope centers on a Formula (I) composition with anesthetic moieties X, photocleavable linkers L, and a block copolymer P comprising at least one polyether. The combined claim set includes 5 inventive features covering the scaffold, light-cleavage condition, polymer component, a Formula (I-a) variant, and pain-treatment use.
Photocleavable anesthetic-linked polymer scaffold
A composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or isotopically enriched derivative, where each instance of X is independently an anesthetic compound, each instance of L is independently a photocleavable linker, and at least one instance of L comprises coumarin, o-nitrobenzyl, benzoin, 7-nitroindoline, or p-hydroxyphenacyl.
Light-cleavable L–X bond by specified absorption wavelength range
The bond between each instance of L and each instance of X is cleaved when illuminated with light having an absorption wavelength of approximately 200 nm to 500 nm.
Polyether-containing block copolymer
P is a block copolymer comprising at least one polyether.
Specific Formula (I-a) variant with defined substituent and integer constraints
The composition includes a Formula (I-a) sub-formula with defined substituent options for R3 and Rb and integer parameters q, r, and s, each constrained as an integer between 0 and 200 with a sum of at least 1.
Pain treatment by administration
A method for treating pain in a subject by administering a therapeutically effective amount of the composition.
The claim scope centers on a Formula (I) scaffold that combines anesthetic moieties X with photocleavable linkers L bearing specified photolabile groups and a polyether-containing block copolymer P. The claims further refine the light-absorption cleavage range, specify poloxamer-based embodiments, add a Formula (I-a) variant, and include treatment of pain by administration.
Stated Advantages
Reduces unwanted initial nerve block and basal drug release by macromolecular conjugation, while enabling light-triggered on-demand drug release.
Provides inactivity without irradiation and enables repeatable triggering.
Documented Applications
Treating and preventing pain, including inflammatory pain, infectious disease pain, ear disease/otitis media pain, dental procedure pain, trauma/injury pain, and sustained pain.
Treating pain in a subject by administering a therapeutically effective amount of the composition.
Combination therapies are described.
Interested in licensing this patent?