# US 11,439,609 B2 · Nitric oxide releasing PLGA microspheres for biomedical applications > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,609 B2 - Document ID: US11439609B2 - Status: Granted - Kind: B2 - Application number: 15/735,122 - Filed: 2016-06-10 - Published: 2019-10-10 - Granted: 2022-09-13 - Earliest claimed: 2015-06-11 - Assignees: The Regents of the University of Michigan - Applicants: The Regents of the University of Michigan - Inventors: Gergely Lautner; Steven P. Schwendeman; Mark E. Meyerhoff - Web page: https://patentgrep.com/patent/US11439609B2 ## CPC - A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)} - A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin - A61L 15/28: Polysaccharides or their derivatives {(A61L15/225 takes precedence)} - A61L 15/52: Water-repellants - A61L 2300/114: Nitric oxide, i.e. NO - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) ## Abstract A polymeric composition includes poly(lactide-co-glycolide) (PLGA) microspheres; and at least one of a discrete RSNO adduct or a polymeric RSNO encapsulated within the microspheres, with the at least one of the discrete RSNO adduct or the polymeric RSNO adduct capable of releasing nitric oxide (NO). The polymeric composition exhibits stability under dry conditions at 37° C. and prolonged and controllable NO release rates, when exposed to light capable of photolyzing an RSNO bond, or when exposed to moisture, for a predetermined amount of time from the at least one of the discrete RSNO adduct or the polymeric RSNO adduct. ## Claims ### Claim 1 A polymeric composition, consisting of: poly(lactide-co-glycolide) microspheres or poly(lactic-co-glycolic acid) microspheres; and S-nitroso-N-acetylpenicillamine (SNAP) or a biodegradable polymer possessing an appended SNAP encapsulated within the poly(lactide-co-glycolide) microspheres or poly(lactic-co-glycolic acid) microspheres by a solid-in-oil-in-water emulsion and solvent evaporation method, wherein the SNAP or the biodegradable polymer possessing the appended SNAP is capable of spontaneously releasing nitric oxide (NO) when exposed to light capable of photolyzing an S-nitrosothiol (RSNO) bond or when exposed to moisture; the polymeric composition to exhibit stability under dry conditions at 37° C., and prolonged and controllable NO release rates, when exposed to the light or the moisture, for a predetermined amount of time. ### Claim 2 (depends on 1) The polymeric composition as defined in claim 1 wherein the poly(lactide-co-glycolide) microspheres consist of at least one of: ester capped poly(lactide-co-glycolide) having a 50:50 ratio of lactic acid monomer to glycolic acid monomer; and acid terminated poly(lactide-co-glycolide) having a 50:50 ratio of lactic acid monomer to glycolic acid monomer. ### Claim 3 (depends on 2) The polymeric composition as defined in claim 2 wherein the polymeric composition exhibits sustained NO release under physiological conditions for an amount of time ranging from about 10 days to about 4 weeks. ### Claim 4 (depends on 1) The polymeric composition as defined in claim 1 wherein the poly(lactide-co-glycolide) microspheres or poly(lactic-co-glycolic acid) microspheres each have an average diameter ranging from about 20 μm to about 125 μm. ### Claim 5 A method for making an NO-releasing polymeric composition, comprising: encapsulating S-nitroso-N-acetylpenicillamine (SNAP) or a biodegradable polymer possessing an appended SNAP within poly(lactide-co-glycolide) microspheres or poly(lactic-co-glycolic acid) microspheres by a solid-in-oil-in-water emulsion and solvent evaporation method, wherein the SNAP or the biodegradable polymer possessing the appended SNAP is capable of spontaneously releasing nitric oxide (NO) when exposed to light capable of photolyzing an S-nitrosothiol (RSNO) bond or when exposed to moisture; the polymeric composition to exhibit stability under dry conditions at 37° C., and prolonged and controllable NO release rates, when exposed to the light or the moisture, for a predetermined amount of time. ### Claim 6 (depends on 5) The method as defined in claim 5 wherein: the SNAP is encapsulated in the poly(lactide-co-glycolide) microspheres; and the poly(lactide-co-glycolide) microspheres comprise at least one of: ester capped poly(lactide-co-glycolide) having a 50:50 ratio of lactic acid monomer to glycolic acid monomer; and acid terminated poly(lactide-co-glycolide having a 50:50 ratio of lactic acid monomer to glycolic acid monomer. ### Claim 7 (depends on 6) The method as defined in claim 6 wherein the polymeric composition exhibits sustained NO release under physiological conditions for an amount of time ranging from about 10 days to about 4 weeks. ### Claim 8 (depends on 1) An NO releasing wound dressing, comprising: a hydrogel film; and the polymeric composition of claim 1 incorporated into the hydrogel film. ### Claim 9 (depends on 1) An NO releasing ointment, comprising: a hydrophobic ointment; and the polymeric composition of claim 1 dispersed within the hydrophobic ointment. ### Claim 10 (depends on 1) An NO releasing fluid, comprising: the fluid including a vehicle, the fluid to be incorporated into a depot injection; and the polymeric composition of claim 1 incorporated into the vehicle. ### Claim 11 (depends on 1) A method for making an NO releasing wound dressing, comprising: dispersing the polymeric composition of claim 1 in an alginate solution to form a dispersion; casting the dispersion into a mold; and drying the cast dispersion to form a layer of a polymer microsphere-alginate composite film; and crosslinking the composite film to form a hydrogel wound dressing material. ### Claim 12 (depends on 1) The polymeric composition as defined in claim 1 wherein the SNAP is encapsulated within the poly(lactide-co-glycolide) microspheres or poly(lactic-co-glycolic acid) microspheres, and wherein an amount of encapsulated SNAP ranges from about 0.3 μmol per mg microsphere to about 0.6 μmol per mg microsphere. ### Claim 13 (depends on 1) The polymeric composition as defined in claim 1 wherein the SNAP is encapsulated within the poly(lactide-co-glycolide) microspheres or poly(lactic-co-glycolic acid) microspheres. ### Claim 14 (depends on 1) The polymeric composition as defined in claim 1 wherein the biodegradable polymer possessing the appended SNAP is encapsulated within the poly(lactide-co-glycolide) microspheres or poly(lactic-co-glycolic acid) microspheres, and wherein the biodegradable polymer is selected from the group consisting of polylactide, polyglycolide (PGA), polycaprolactone, copolymers thereof, and mixtures thereof. ### Claim 15 (depends on 13) The polymeric composition as defined in claim 13 wherein the SNAP is non-dissolved, crystalline SNAP. ### Claim 16 (depends on 15) The polymeric composition as defined in claim 15 wherein a loading of the SNAP does not decrease below 90% after a one-month storage period in dark conditions at room temperature. ### Claim 17 (depends on 15) The polymeric composition as defined in claim 15 wherein a loading of the SNAP does not decrease below 70% after a one year storage period in dark conditions at 37° C.