Biomimetic boundary lubricants for articular cartilage

Patent metadata

Field	Value
Publication number	US-10344243-B2
Application number	US-201314436677-A
Country	US
Kind code	B2
Filing date	Oct 18, 2013
Priority date	Oct 19, 2012
Publication date	Jul 9, 2019
Grant date	Jul 9, 2019

Abstract

This invention relates to methods of lubrication for biological tissue, especially joint and cartilage surfaces, and to methods of treating osteoarthritis using high molecular weight, hydrophilic polymer brushes, which mimic the structure and activity of lubricin. These synthetic lubricin analog polymer brushes (termed herein graft brush polymers), include poly(acrylic acid) backbones grafted with polyethylene glycol.

First claim

We claim:

1. A graft brush polymer comprising (i) a polyacrylic (PAA) backbone having a polydispersity index ranging from 1.0 to about 1.5 and a molecular weight of about 60 kDa, (ii) polyethylene glycol (PEG) brush segments having a molecular weight of about 2 kDa, and (iii) at least one functionalizable group, selected from thiol and amine groups, located on at least one of the two terminal ends of the PAA backbone, wherein said graft brush polymer has a PEG:AA grafting ratio of about 2, wherein the grafting ratio is defined as the moles of PEG grafted to the PAA backbone divided by the moles of acrylic acid (AA) monomers in the PAA backbone.

2. The polymer of claim 1 , wherein said functionalizable terminal group is a thiol group.

3. The polymer of claim 2 , wherein a cartilage binding domain is attached to said polymer via said thiol group.

4. The polymer of claim 3 , wherein said cartilage binding domain is a peptide moiety selected from the group consisting of TKKTLRT (SEQ ID NO: 1), SQNPVQP (SEQ ID NO: 2), WYRGRL (SEQ ID NO: 3), SYIRIADTN (SEQ ID NO: 4) and CQDSETRFY (SEQ ID NO: 5).

5. The polymer of claim 1 , wherein said graft brush copolymer further comprises at least one binding agent that can bind the graft brush copolymer to a biological tissue.

6. The polymer of claim 5 , wherein said binding agent is a hydrophobic alkane chain or a sterol.

7. A pharmaceutical composition comprising the graft brush copolymer of claim 1 and a pharmaceutically-acceptable carrier.

Assignees

• Univ Cornell

Inventors

• Putnam David
• Tan Mingchee
• Samaroo Kirk J
• Bonassar Lawrence J

Classifications

• A61F2002/30673

  Lubricating means, e.g. synovial pocket · CPC title

• A61F2/30756

  Cartilage endoprostheses (A61F2/3603 takes precedence) · CPC title

• A61K47/66

  the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells · CPC title

• C10M107/28 Primary

  containing monomers having an unsaturated radical bound to a carboxyl radical, e.g. acrylate · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title