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US 12,758,496 B2Granted
Polyfunctional radical scavenger hydrogel formulation
AssigneeRXOS Medical, Inc.
InventorsRichard M Millis, Jeffrey A Niezgoda, Rajagopalan Sridhar
Life of this patent
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Abstract
A polyfunctional radical scavenger hydrogel formulation providing extended protection of the extracellular space within a wound site. The polyfunctional radical scavenger hydrogel formulation is generally formed from a hydrogel, a first radical scavenger and a second radical scavenger differing from the first radical scavenger with respect to at least one property. A portion of the first radical scavenger included with the formation and/or second radical scavenger included within the formulation may be dissolved, suspended and/or bonded to a polymer of the hydrogel.
Claims20
A method comprising the step of:
- contacting a polyfunctional free radical scavenger hydrogel composition with a wounded tissue;
- and
- wherein the polyfunctional free radical scavenger hydrogel composition comprises:
- a hydrogel;
- a first free radical scavenger, and a second free radical scavenger and wherein the first free radical scavenger comprises a sterically hindered amine of the general formula:
- wherein R1-1 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R2-1 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R3-1 is selected from the group consisting of H and a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R4-1 is selected from the group consisting of H and a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein X1-1 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide,
- wherein X2-1 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide,
- wherein X3-1 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide,
- wherein X4-1 is selected from the group consisting of H, OH, {dot over (O)} and O;
- and
- the second free radical scavenger is lipid soluble and wherein the second free radical scavenger is present in an amount to provide protection against reactive oxygen species within the wounded tissue, the second free radical scavenger comprising a sterically hindered nitrone of the general formula:
- wherein R1-4 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R2-4 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R3-4 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein X1-4 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide,
- wherein X2-4 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide,
- wherein X3-4 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide, and
- wherein Y is an aromatic moiety Y comprising one or more substituents that (1) increases lipid solubility;
- (2) limits cellular uptake across at least one cellular member within a wound site;
- or (3) both increases lipid solubility and limits cellular uptake across at least one cellular member within a wound site.
21 more elements
A method of treating a wound site comprising wounded tissue in a human comprising the step of:
- applying a hydrogel composition to the wounded tissue;
- and
- wherein the hydrogel composition comprises:
- a hydrogel, a plurality of free radical scavengers comprising a hydroxylamine and a sterically hindered nitrone;
- wherein the hydroxylamine and the sterically hindered nitrone extend the protection of an extracellular space of the wound site by either:
- (1) the hydroxylamine kinetically protecting the sterically hindered nitrone from degradation or (2) the hydroxylamine and the sterically hindered nitrone are both bonded to a polymer of the hydrogel composition or another molecule such that the hydroxylamine has a zone of influence and the sterically hindered nitrone has a zone of influence and the zone of Influence of the hydroxylamine and the zone of influence of the nitrone are partially overlapping so that a first portion of the zone of influence of the sterically hindered nitrone is unaffected by the presence of the hydroxylamine while at the same time a second portion of the zone of influence of the sterically hindered nitrone is kinetically protected by the hydroxylamine from being degraded by at least one reactive oxygen species within the wound site;
- and
- wherein the sterically hindered nitrone is of the general formula:
- wherein R1-4 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R2-4 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R3-4 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein X1-4 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide,
- wherein X2-4 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide,
- wherein X3-4 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide, and
- wherein Y is an aromatic moiety Y comprising one or more substituents that (1) increases lipid solubility;
- (2) limits cellular uptake across at least one cellular member within a wound site;
- or (3) both increases lipid solubility and limits cellular uptake across at least one cellular member within a wound site.
14 more elements
A method of treating a wound comprising the step of:
- applying a polyfunctional free radical scavenger hydrogel composition to a wound;
- and
- wherein the polyfunctional free radical scavenger hydrogel composition comprises a hydrogel;
- and a plurality of free radical scavengers that provide protection against reactive oxygen species within a wound;
- wherein the plurality of free radical scavengers is suspended or dissolved in the hydrogel and comprise a first free radical scavenger and a second free radical scavenger that is a lipid soluble nitrone comprising an aromatic moiety that (1) increases lipid solubility;
- (2) limits cellular uptake across at least one cellular member within a wound site;
- or (3) both increases lipid solubility and limits cellular uptake across at least one cellular member within a wound site;
- and
- wherein the first free radical scavenger present in an amount providing protection of the wound against reactive oxygen species within the wound, the first free radical scavenger comprising a sterically hindered amine of the general formula:
- wherein R1-1 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R2-1 is a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R3-1 is selected from the group consisting of H and a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein R4-1 is selected from the group consisting of H and a carbon chain having a length of C1 to C12, wherein the carbon chain is linear, branched, cyclic, aromatic portion, or a combination thereof,
- wherein X1-1 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide;
- wherein X2-1 is selected from the group consisting of H, OH, acrylate, methacrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide;
- wherein X3-1 is selected from the group consisting of H, OH, acrylate, N-(alkylcarboxyl)-acrylamide, and N-(alkyl carboxyl)-methacrylamide;
- and
- wherein X4-1 is selected from the group consisting of H, OH, {dot over (O)} and O—.
15 more elements
Dependencies are inferred from the claim text.