Hydrogel implants with varying degrees of crosslinking

Patent metadata

Field	Value
Publication number	US-9468684-B2
Application number	US-201514614813-A
Country	US
Kind code	B2
Filing date	Feb 5, 2015
Priority date	May 27, 2010
Publication date	Oct 18, 2016
Grant date	Oct 18, 2016

Abstract

The present disclosure relates to a hydrogel composition and methods of using the same. The hydrogel composition may include precursors that react with each other upon contact as well as precursors that react upon contact with an initiator. In embodiments, the resulting hydrogels may have varying levels of crosslinking with both denser and less dense regions.

First claim

What is claimed:

1. A hydrogel composition comprising:
a first hydrogel comprising a first reactive precursor comprising a multi-arm polyether possessing electrophilic groups, a second reactive precursor comprising nucleophilic groups, and at least one bioactive agent; and
a barrier layer on an external surface of the first hydrogel, the barrier layer comprising at least one initiated precursor selected from the group consisting of phosphorylcholine containing monomers, furanone functional vinyl monomers, N-vinyl pyrrolidone, siloxane functional vinyl compounds, polyethylene glycol-silicone co-monomers having vinyl groups, pyrrole, liquid crystalline vinyl monomers, liquid crystalline vinyl polymers, and combinations thereof,
wherein the barrier layer directs delivery of the bioactive agent from the first hydrogel in a direction opposite the barrier layer.

2. The hydrogel composition of claim 1 , wherein the first reactive precursor is reactive with the second reactive precursor to form the first hydrogel possessing the bioactive agent, and the initiated precursor forms the barrier layer on the external surface of the first hydrogel upon exposure with an initiator.

3. The hydrogel composition of claim 1 , wherein the first reactive precursor comprises a core selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, and combinations thereof, and wherein the second reactive precursor comprises a core comprising a component selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, polyvinyl alcohol, poly(vinyl pyrrolidinone), poly(amino acids), dextran, chitosan, alginates, carboxymethylcellulose, oxidized cellulose, hydroxyethylcellulose, hydroxymethylcellulose, hyaluronic acid, albumin, collagen, casein, gelatin, and combinations thereof.

4. The hydrogel composition of claim 1 , wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.

5. The hydrogel composition of claim 2 , wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, and combinations thereof.

6. The hydrogel composition of claim 1 , wherein the initiated precursor comprises from about 5% to about 30% by weight of the hydrogel composition.

7. The hydrogel composition of claim 1 , wherein the first hydrogel has a modulus of from about 5 kPa to about 90 kPa, and the barrier layer has a modulus of from about 50 kPa to about 5,000 kPa.

8. The hydrogel composition of claim 1 , wherein the first hydrogel degrades over a period of from about 1 week to about 12 weeks, and the barrier layer degrades over a period of at least about 2 weeks.

9. The hydrogel composition of claim 1 , wherein the first hydrogel is a component of a composition selected from the group consisting of adhesives, hemostats, sealants, implants, protective barriers, drug delivery devices, and combinations thereof.

10. The hydrogel composition of claim 1 , further comprising a visualization agent.

11. The hydrogel composition of claim 1 , wherein the bioactive agent is selected from the group consisting of anti-adhesives, antimicrobials, analgesics, antipyretics, anesthetics, antiepileptics, antihistamines, anti-inflammatories, cardiovascular drugs, diagnostic agents, sympathomimetics, cholinomimetics, antimuscarinics, antispasmodics, hormones, growth factors, muscle relaxants, adrenergic neuron blockers, antineoplastics, immunogenic agents, immunosuppressants, gastrointestinal drugs, diuretics, steroids, lipids, lipopolysaccharides, polysaccharides, platelet activating drugs, clotting factors, enzymes, and combinations thereof.

12. The hydrogel composition of claim 1 , wherein the bioactive agent is selected from the group consisting of local anesthetics, non-steroidal antifertility agents, parasympathomimetic agents, psychotherapeutic agents, tranquilizers, decongestants, sedative hypnotics, steroids, sulfonamides, sympathomimetic agents, vaccines, vitamins, antimalarials, anti-migraine agents, anti-parkinson agents, anti-spasmodics, anticholinergic agents, antitussives, bronchodilators, coronary vasodilators, nitroglycerin, alkaloids, analgesics, narcotics, non-narcotics, opioid receptor antagonists, anti-cancer agents, anti-convulsants, anti-emetics, antihistamines, anti-inflammatory agents, prostaglandins, cytotoxic drugs, chemotherapeutics, estrogens, antibacterials, antibiotics, anti-fungals, anti-virals, anticoagulants, anticonvulsants, antidepressants, antihistamines, immunological agents, and combinations thereof.

13. The hydrogel composition of claim 1 , wherein the bioactive agent is selected from the group consisting of viruses, cells, peptides, polypeptides, proteins, immunoglobulins, antibodies, cytokines, blood clotting factors, hemopoietic factors, interleukins, interferons, erythropoietin, nucleases, tumor necrosis factor, colony stimulating factors, insulin, anti-tumor agents, tumor suppressors, blood proteins, gonadotropins, hormones, hormone analogs, vaccines, somatostatin, antigens, blood coagulation factors, growth factors, bone morphogenic proteins, transforming growth factor beta, protein inhibitors, protein antagonists, protein agonists, nucleic acids, antisense molecules, deoxyribonucleic acid, ribonucleic acid, oligonucleotides, polynucleotides, ribozymes, and combinations thereof.

Assignees

• Covidien Lp

Inventors

• Bennett Steven
• Mast Nathaniel
• Lavigne Kevin
• Skalla Walter

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title