Absorbable polyurethanes and methods of use thereof

Abstract

Disclosed are novel bioabsorbable and biodegradable monomer compounds, bioabsorbable and biodegradable polymers therefrom, and methods of making such monomers and polymers, which are useful in pharmaceutical delivery systems, tissue engineering applications, tissue adhesives products, implantable medical devices, foams and reticulated foams for wound healing and drug delivery, bone hemostats and bone void fillers, adhesion prevention barriers, meshes, filters, stents, medical device coatings, pharmaceutical drug formulations, consumer product and cosmetic and pharmaceutical packaging, apparel, infusion devices, blood collection tubes and devices, other medical tubes, skin care products, and transdermal drug delivery materials.

1 - 20 . (canceled) 
     
     
         21 . A diisocyanate or diamine selected from the group consisting of the structures having formulas (8)-(15) and (23)-(30): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein: 
       each X independently is selected from:
 —CH 2 COO—; 
 —CH(CH 3 )COO—; 
 —CH 2 CH 2 OCH 2 COO—; 
 —CH 2 CH 2 CH 2 CH 2 CH 2 COO—; 
 —(CH 2 ) y COO—, where y is an integer selected from 2, 3, 4, and 6-24 inclusive; and 
 —(CH 2 CH 2 O) z ′CH 2 COO—, where z′ is an integer between 2-24, inclusive; 
 
       each X′ independently is selected from:
 —OOCCH 2 —; 
 —OOC(CH 3 )CH—; 
 —OOCCH 2 OCH 2 CH 2 —; 
 —OOCCH 2 CH 2 CH 2 CH 2 CH 2 —; 
 —OOC(CH 2 )y-, where y is an integer selected from 2, 3, 4, and 6-24 inclusive; and 
 —OOCCH 2 (OCH 2 CH 2 )z′- where z′ is an integer between 2-24, inclusive; 
 
       each X″ independently is selected from:
 —OCH 2 CO—; 
 —OCH(CH 3 )CO—; 
 —OCH 2 CH 2 OCH 2 CO—; 
 —OCH 2 CH 2 CH 2 CH 2 CH 2 CO—; 
 —O(CH 2 ) y CO—, where y is an integer selected from 2, 3, 4, and 6-24 inclusive; and 
 —O(CH 2 CH 2 O) z ′CH 2 CO—, where z′ is an integer between 2-24, inclusive; 
 
       each Y independently is selected from:
 —COCH 2 O—; 
 —COCH(CH 3 )O—; 
 —COCH 2 OCH 2 CH 2 O—; 
 —COCH 2 CH 2 CH 2 CH 2 CH 2 O—; 
 —CO(CH 2 ) m O—, where m is an integer selected from 2, 3, 4, and 6-24 inclusive; and 
 —COCH 2 O(CH 2 CH 2 O) n — where n is an integer between 2-24, inclusive; 
 
       each Y′ independently is selected from:
 —OCH 2 OC—; 
 —O(CH 3 )CHOC—; 
 —OCH 2 CH 2 OCH 2 OC—; 
 —OCH 2 CH 2 CH 2 CH 2 CH 2 OC—; 
 —O(CH 2 ) m OC— where m is an integer selected from 2, 3, 4, and 6-24 inclusive; and 
 —(OCH 2 CH 2 ) n OCH 2 OC— where n is an integer between 2-24 inclusive; 
 
       each Z independently is selected from: —O—, —S—, and —NH—; 
       each R independently is a phenylene group or a straight-chained or branched alkylene group, these groups optionally contain one or more oxygen atoms, sulfur atoms, halogen atoms, ester groups, or aromatic groups; 
       each Rn is independently selected from one or more members selected from: H, alkoxy, benzyloxy, aldehyde, halogen, carboxylic acid, and —NO 2 ; and, 
       Rn is attached directly to the aliphatic ring or attached through an alkylene chain. 
     
     
         22 . The diisocyanate or diamine of  claim 21 , wherein:
 each X independently is selected from: —CH 2 COO—; —CH(CH 3 )COO—; —CH 2 CH 2 OCH 2 COO—; and, —CH 2 CH 2 CH 2 CH 2 CH 2 COO—;   each X′ independently is selected from: —OOCCH 2 —; —OOC(CH 3 )CH—; —OOCCH 2 OCH 2 CH 2 —; and, —OOCCH 2 CH 2 CH 2 CH 2 CH 2 —;   each X″ independently is selected from: —OCH 2 CO—; —OCH(CH 3 )CO—; —OCH 2 CH 2 OCH 2 CO—; and —OCH 2 CH 2 CH 2 CH 2 CH 2 CO—;   each Y independently is selected from: —COCH 2 O—; —COCH(CH 3 )O—; —COCH 2 OCH 2 CH 2 O—;   and —COCH 2 CH 2 CH 2 CH 2 CH 2 O—;   each Y′ independently is selected from: —OCH 2 CO—; —OCH(CH 3 )CO—; —OCH 2 CH 2 OCH 2 CO—; and —OCH 2 CH 2 CH 2 CH 2 CH 2 CO—;   each Z independently is selected from: —O—, —S—, and —NH—;   each R is independently a straight-chained or branched alkylene containing 1-24 carbon atoms and optionally containing one or more moieties selected from: an oxygen atom, a sulfur atom, an ester group, an aromatic group, and a halogen atom;   each p is independently an integer between 0 and 4, inclusive; and,   each Rn is independently selected from one or more members selected from: H, alkoxy, benzyloxy, aldehyde, halogen, carboxylic acid, and —NO 2 ;   Rn is attached directly to the aliphatic ring or attached through an alkylene chain.   
     
     
         23 . An absorbable polymer prepared from at least one diisocyanate or diamine compound of  claim 21 . 
     
     
         24 . The absorbable polymer of  claim 23 , comprising a polymer selected from the group consisting of polyurethanes, polyamides, polyester urethanes and polyesteramides. 
     
     
         25 . An article comprising a metal or polymeric substrate having thereon a coating comprising: at least one polymer according to  claim 23 , wherein said article contacts mammalian tissue. 
     
     
         26 . The article of  claim 25 , wherein said article is an implantable medical device. 
     
     
         27 . A controlled drug delivery system comprising:
 (1) one or more polymers according to  claim 23 , and   (2) one or more biologically or pharmacologically active agents.   
     
     
         28 . The controlled drug delivery system of  claim 27 , wherein said one or more biologically or pharmacologically active agents are physically embedded or dispersed in a polymeric matrix comprising said one or more polymers. 
     
     
         29 . A tissue scaffold comprising one or more polymers according to  claim 23 , wherein said tissue scaffold has a porous structure for the attachment and proliferation of cells, either in vitro or in vivo. 
     
     
         30 . The polymer according to  claim 23 , wherein said polymer is further polymerized on at least one end with polyesters of at least one lactone monomer selected from the group consisting of glycolide, lactide, p-dioxanone, trimethylene carbonate and caprolactone. 
     
     
         31 . An article comprising a metal or polymeric substrate wherein said article is used in
 (a) medicinal, medical device, therapeutic, consumer product, cosmetic or tissue engineering applications, or   (b) wound healing and/or controlled drug delivery, and comprises a foam, or   (c) sutures, bone hemostats, bone fillers, bone void fillers, bone cements, tissue adhesives, tissue sealants, adhesion prevention barriers, meshes, or filters, or   (d) stents, medical device coatings, pharmaceutical drug formulations, cosmetic packaging, pharmaceutical packaging, apparel, infusion devices, blood collection devices, tubes, skin care products or transdermal drug delivery materials, and   wherein said article comprises at least one polymer according to  claim 23 .   
     
     
         32 . The article of  claim 31 (b), wherein said foam comprises a reticulated foam.