US2019194564A1PendingUtilityA1

Biomimetic boundary lubricants for articular cartilage

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Assignee: UNIV CORNELLPriority: Oct 19, 2012Filed: Dec 27, 2018Published: Jun 27, 2019
Est. expiryOct 19, 2032(~6.3 yrs left)· nominal 20-yr term from priority
Inventors:David PutnamMingchee TanKirk J. SamarooLawrence Bonassar
A61K 31/795A61L 2430/24A61K 47/66A61F 2002/30754A61F 2002/30673C10M 107/28A61L 27/3604A61K 31/728A61L 2400/06A61L 27/3695A61F 2/30756A61P 19/02
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Claims

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.

Claims

exact text as granted — not AI-modified
1 . A method for imparting a suitable level of lubricity to a biological tissue which comprises contacting said biological tissue with an sufficient amount of a composition to impart suitable lubricity, said composition comprising a graft brush copolymer with a pAA backbone or a graft brush copolymer comprising (i) a polyanionic backbone having a polydispersity index ranging from 1.0 to about 1.5 and a molecular weight ranging from about 50 kDa to about 200 kDa, (ii) brush segments having a molecular weight ranging from about 1 kDa to about 20 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 polyanionic backbone. 
     
     
         2 . The method of  claim 1 , wherein contacting is by injecting, infusing, implanting, coating or spraying. 
     
     
         3 . The method of  claim 1 , wherein said biological tissue is selected from joints and cartilage. 
     
     
         4 . The method of  claim 1 , wherein said biological tissue is a joint. 
     
     
         5 . The method of  claim 4 , wherein said joint is an injured joint or an arthritic joint. 
     
     
         6 . The method of  claim 4 , wherein said biological tissue is ocular, nasal, a tendon, a tendon capsule or vaginal tissue. 
     
     
         7 . The method of  claim 1 , wherein said polyanionic backbone has a molecular weight ranging from about 50 kDa to about 150 kDa. 
     
     
         8 . The method of  claim 7 , wherein said polyanionic backbone has a molecular weight range ranging from about 50 kDa to about 100 kDa. 
     
     
         9 . The method of  claim 7 , wherein said polyanionic backbone has a molecular weight range ranging from about 50 kDa to about 75 kDa. 
     
     
         10 . The method of  claim 1 , wherein said polymer is a poly(acrylic acid)-graft-poly(ethylene glycol) brush polymer. 
     
     
         11 . A method for treating osteoarthritis which comprises administering to an arthritic or an injured joint of a patient a therapeutically-effective amount of a graft brush copolymer to impart a suitable level of lubricity to said arthritic or injured joint, said graft brush copolymer comprising a pAA backbone or a graft brush copolymer comprising (i) a polyanionic backbone having a polydispersity index ranging from 1.0 to about 1.5 and a molecular weight ranging from about 50 kDa to about 200 kDa, (ii) brush segments having a molecular weight ranging from about 1 kDa to about 20 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 polyanionic backbone. 
     
     
         12 . The method of  claim 11 , which comprises simultaneously or sequentially administering hyaluronic acid to said joint. 
     
     
         13 . The method of  claim 11 , wherein administering is by injecting or infusing. 
     
     
         14 . The method of  claim 11 , wherein said polyanionic backbone is polyacrylic acid. 
     
     
         15 . The method of  claim 11 , wherein said polyanionic backbone has a molecular weight ranging from about 50 kDa to about 150 kDa. 
     
     
         16 . The method of  claim 11 , wherein said brush segments are polyethylene glycol or dextran. 
     
     
         17 . The method of  claim 16 , wherein said brush segments are polyethylene glycol. 
     
     
         18 . The method of  claim 17 , wherein said polyethylene glycol has a molecular weight selected from the group consisting of about 1 kDa, about 2 kDa, about 5 kDa or about 10 kDa. 
     
     
         19 . The method of  claim 11 , wherein said functionalizable terminal group is a thiol group. 
     
     
         20 . The method of  claim 19 , wherein a cartilage binding domain is attached to said polymer via said thiol group. 
     
     
         21 . The method of  claim 11 , wherein said copolymer is a poly(acrylic acid)-graft-poly(ethylene glycol) brush polymer. 
     
     
         22 .- 38 . (canceled) 
     
     
         39 . The method of  claim 11 , wherein said polyanionic backbone has a molecular weight range ranging from about 50 kDa to about 100 kDa. 
     
     
         40 . The method of  claim 11 , wherein said polyanionic backbone has a molecular weight range ranging from about 50 kDa to about 75 kDa.

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