Hydrogel materials incorporating eluting ceragenin compound

Patent metadata

Field	Value
Publication number	US-10676501-B2
Application number	US-201213554930-A
Country	US
Kind code	B2
Filing date	Jul 20, 2012
Priority date	Jul 20, 2011
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

A hydrogel polymer includes a ceragenin compound. The ceragenin compound has a hydrophobicity/hydrophilicity that produces a release rate in a range of 0.1-100 μg/ml for at least 3 days.

First claim

What is claimed is:

1. A ceragenin eluting hydrogel material, comprising
a hydrogel polymer selected from the group consisting of polyvinyl alcohol, sodium polyacrylate, acrylate polymers, poly(2-acrylamido-2-methyl-1-propanesulfonic acid (polyAMPS), polyvinylpyrrolidone, polyacrylamide, silicone, agarose, methylcellulose, hyaluronan, hydrolyzed polyacrylicnitrile, cross-linked polymers based on hydrophilic derivatives of acrylic or methacrylic acid, and cross-linked polymers based on hydrophilic vinylic monomers, and combinations of the foregoing;
at least 50% by weight water absorbed into the hydrogel polymer; and
a ceragenin compound mixed with the hydrogel polymer and non-covalently bonded thereto, the ceragenin compound comprising a hydrophobic sterol backbone, a hydrophobic substituent joined to the sterol backbone, and a plurality of hydrophilic cationic groups, wherein the ceragenin compound is anti-bacterial, anti-viral, or anti-fungal, wherein the ceragenin eluting hydrogel material forms at least an outer surface of a medical device, contact lens, or other substrate having a fixed shape and structure,
wherein hydrophobic/hydrophilic interactions between the ceragenin compound and the hydrogel polymer control the rate of elution of the ceragenin compound from the hydrogel polymer when the outer surface of the medical device, contact lens, or other substrate is exposed to water and/or microbes so that the ceragenin compound controllably elutes from the hydrogel material in excess water at a rate of 0.1-100 μg/ml at 3 days, one week, or one month and/or over a period of 3 days, one week and/or one month,
wherein at last a portion of the hydrogel material is coated on a medical device, contact lens, or other substrate of fixed shape and structure.

2. A ceragenin eluting hydrogel material as in claim 1 , wherein the ceragenin compound elutes from the hydrogel material in excess water at a rate of 1-10 μg/ml at 3 days, one week, or one month and/or over a period of 3 days, one week and/or one month.

3. A ceragenin eluting hydrogel material as in claim 1 , wherein the hydrogel material comprises at least 90% by weight water absorbed into the hydrogel polymer.

4. A ceragenin eluting hydrogel material as in claim 1 , wherein the water is a saline water.

5. A ceragenin eluting hydrogel material as in claim 1 , wherein the hydrogel polymer includes polyvinyl alcohol, sodium polyacrylate, an acrylate polymer, polyethylene oxide, polyAMPS, polyvinylpyrrolidone, polyacrylamide, silicone, agarose, methylcellulose, hyaluronan, or a combination thereof.

6. A ceragenin eluting hydrogel material as in claim 1 , wherein the hydrophobic substituent includes a carbon chain of at least 9 carbons.

7. A ceragenin eluting hydrogel material as in claim 1 , having a structure as in Formula I:

wherein,
q=0 and p=1;
R 3 , R 7 , and R 12 independently include a cationic group; and
R 17 is a hydrophobic substituent comprising one or more heteroatoms selected from O or N and at least one carbon chain of at least 9 carbons extending from the heteroatom.

8. A ceragenin eluting hydrogel material as in claim 1 , wherein a portion of the hydrogel material is formed into a structure of the medical device, contact lens, or other substrate of fixed shape and structure.

9. A ceragenin eluting hydrogel material as in claim 1 , wherein the medical device is selected from the group consisting of bone implant, bone pin, bone screw, tissue graft, endotracheal tube, coronary stent, peripheral stent, catheter, arterio-venous graft, by-pass graft, pacemaker or defibrillator lead, anastomotic clip, arterial closure device, patent foramen ovale closure device, and drug delivery balloon.

10. A ceragenin eluting hydrogel material as in claim 1 , wherein the type and concentration of the ceragenin compound is selected to provide a minimum inhibition concentration sufficient to inhibit the growth of Staphylococcus aureus type methicillin-resistant Staphylococcus aureus or vancomycin-resistant Staphylococcus aureus under physiological conditions.

11. The ceragenin eluting hydrogel material of claim 10 , wherein the hydrogel material comprises silicone.

12. A ceragenin eluting hydrogel material, comprising:
a hydrogel polymer; and
a ceragenin compound incorporated into the hydrogel polymer and non-covalently bonded thereto, the ceragenin compound comprising a hydrophobic sterol backbone, a hydrophobic substituent joined to the sterol backbone, and a plurality of hydrophilic cationic groups, wherein the ceragenin compound is anti-bacterial, anti-viral, or anti-fungal,
wherein a first portion of the ceragenin eluting hydrogel material is formed into a shape and structure of a medical device, contact lens, or other substrate of fixed shape and structure,
wherein a second portion of the ceragenin eluting hydrogel material is coated on the medical device, contact lens, or other substrate of fixed shape and structure,
wherein hydrophobic/hydrophilic interactions between the ceragenin compound and the hydrogel polymer control the rate of elution of the ceragenin compound from the hydrogel polymer when the hydrogen material is exposed to water and/or microbes so that the ceragenin compound controllably elutes from the hydrogel material in excess water at a rate of 0.1-100 μg/ml at 3 days, one week, or one month and/or over a period of 3 days, one week and/or one month.

13. The ceragenin eluting hydrogel material of claim 12 , wherein the ceragenin compound is selected from the group consisting of CSA-131, CSA-132, CSA-133, CSA-134, CSA-135, CSA-137, and CSA-138.

14. The ceragenin eluting hydrogel material as in claim 12 , wherein the hydrogel material forms the shape and structure of a contact lens.

15. The ceragenin eluting hydrogel material of claim 1 , wherein the ceragenin compound is selected from the group consisting of CSA-44, CSA-142, CSA-144, and CSA-146.

16. A ceragenin eluting hydrogel material forming a coating on an outer surface of a medical device, contact lens, or other substrate of fixed shape and structure, the ceragenin eluting hydrogel material comprising
a hydrogel polymer selected from the group consisting of polyvinyl alcohol, sodium polyacrylate, acrylate polymers, poly(2-acrylamido-2-methyl-1-propanesulfonic acid (polyAMPS), polyvinylpyrrolidone, polyacrylamide, silicone, agarose, methylcellulose, hyaluronan, hydrolyzed polyacrylicnitrile, cross-linked polymers based on hydrophilic derivatives of acrylic or methacrylic acid, cross-linked polymers based on hydrophilic vinylic monomers, and combinations of the foregoing; and
a ceragenin compound mixed with the hydrogel polymer and non-covalently bonded thereto, the ceragenin compound comprising a hydrophobic sterol backbone, a hydrophobic substituent joined to the sterol backbone, and a plurality of hydrophilic cationic groups, wherein the ceragenin compound is both anti-bacterial and anti-fungal,
wherein hydrophobic/hydrophilic interactions between the ceragenin compound and the hydrogel polymer control the rate of elution of the ceragenin compound from the hydrogel polymer when exposed to water and/or microbes so that the ceragenin compound controllably elutes from the hydrogel material in excess water at a rate of 0.1-100 μg/ml at 3 days, one week, or one month and/or over a period of 3 days, one week and/or one month.

17. The ceragenin eluting hydrogel material of claim 16 , wherein the ceragenin compound is selected from the gro

Assignees

• Savage Paul B
• Univ Brigham Young

Inventors

• Savage Paul B

Classifications

• A61L31/10

  Macromolecular materials · CPC title

• A61L2300/404

  Biocides, antimicrobial agents, antiseptic agents · CPC title

• A61L31/04

  Macromolecular materials · CPC title

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61L27/18

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title