P
USRE40359EExpiredUtilityPatentIndex 82

Polymer blends as biodegradable matrices for preparing biocomposites

Assignee: SURMODICS INCPriority: Jan 11, 2000Filed: Mar 8, 2006Granted: Jun 3, 2008
Est. expiryJan 11, 2020(expired)· nominal 20-yr term from priority
Inventors:KATSARAVA RAMAZALAVIDZE ZEMPHIRA
A61L 2103/05A23B 2/7295A23B 2/783A61L 2/00A01N 63/50A61L 15/225A61L 2/18A23B 7/155A61L 15/44A01N 63/40A61L 26/0066A61L 2300/404A61K 9/1641C08G 69/44A61K 47/34A61L 26/0052A61L 2/22C08L 77/12A61L 15/38A61K 9/7007A61L 2300/402A61L 15/26A61L 26/0019A23B 4/22A23G 9/30A61K 9/1694
82
PatentIndex Score
13
Cited by
46
References
66
Claims

Abstract

The present invention provides bioerodable constructs for controlled release of bioactive materials. In a preferred mode, the constructs may be utilized adjacent to a biological surface. The constructs are based on a blend of two or more poly(ester-amide) polymers (PEA). Such polymers may be prepared by polymerization of a diol (D), a dicarboxylic acid (C) and an alpha-amino acid (A) through ester and amide links in the form (DACA) n . An example of a (DACA) n polymer is shown below in formula II. Suitable amino acids include any natural or synthetic alpha-amino acid, preferably neutral amino acids.

Claims

exact text as granted — not AI-modified
1. A bioerodable construct for controlled release of bioactive materials, said construct comprising a blend of at least two poly(ester-amide) polymers (PEA) prepared by polymerizing a diol (D), wherein the diol (D) is not bisphenol; a dicarboxylic acid (C), wherein the dicarboxylic acid (C) is not phthalic acid; and an alpha-amino acid (A) through ester and amide links in the form (DACA) n . ,
 wherein the PEA polymer has the formula: 
                   
 wherein 
 k= 2 - 12 ,  
 m= 2 - 12 , and  
 R=CH 2 CH(CH 3 ) 2 , or CH 2 C 6 H 5 .  
 
 and,  
 wherein the blend comprises a first PEA polymer in which A is phenylalanine (Phe-PEA) and a second PEA polymer in which A is leucine (Leu-PEA) at a ratio of Phe-PEA to Leu-PEA is from  of 10:1 to 1:1.  
 
     
     
       2. The construct of  claim 1 , wherein k= 2 ,  3 ,  4 , and  6  and m= 4  or  8 . 
     
     
       3. The construct of  claim 1 , wherein the ratio of Phe-PEA to Leu-PEA is 5:1 to 2.5:1. 
     
     
       4. The construct according to any one of claims  1 , 2   or  3 , wherein the construct is a deformable sheet adapted to conform to a biological surface. 
     
     
       5. The construct according to  claim 4 , further comprising a bioactive agent. 
     
     
       6. The construct of  claim 5 , wherein the bioactive agent is selected from the group consisting of antiseptics, anti-infectives, such as bacteriophages, antibiotics, antibacterials, antiprotozoal agents, and antiviral agents, analgesics, anti-inflammatory agents including  selected from the group consisting of steroids and non-steroidal anti-inflammatory agents including  selected from the group consisting of COX-2 inhibitors, anti-neoplastic agents, contraceptives, CNS active drugs, hormones, and vaccines. 
     
     
       7. The construct according to  claim 5 , wherein the construct comprises an enzyme capable of hydrolytically cleaving the PEA polymer. 
     
     
       8. The construct according to  claim 7 , wherein the enzyme is α-chymotrypsin. 
     
     
       9. The construct according to  claim 7 , wherein the enzyme is adsorbed on the surface of the construct. 
     
     
       10. The construct according to  claim 7 , wherein the construct contains a bacteriophage which are  is released by action of the enzyme. 
     
     
       11. A method of treating a patient having an ulcerative wound comprising inserting into the wound or covering the wound with a bioerodable construct according to  claim 1 , wherein the bioerodable construct is a deformable sheet containing a bioactive agent. 
     
     
       12. The method of  claim 11 , wherein the bioactive agent is  comprises a bacteriophage, an antibiotic, an antiseptic, or an analgesic. 
     
     
       13. The method of  claim 11 , wherein the wound is open or infected. 
     
     
       14. The method according to  claim 12 , wherein the bacteriophage are specific for bacteria found in the wound. 
     
     
       15. The method according to any one of claim  claims  11 - 14 , wherein the construct also comprises an enzyme capable of hydrolytically clearing the PEA polymer. 
     
     
       16. The construct according to any one of claims  1 ,  2   or  3 , further comprising a bioactive agent. 
     
     
       17. The construct of  claim 16 , wherein the bioactive agent is selected from the group consisting of antiseptics, anti-infectives, such as  bacteriophages, antibiotics, antibacterials, antiprotozoal agents, and antiviral agents, analgesics, anti-inflammatory agents including  selected from the group consisting of steroids and non-steroidal anti-inflammatory agents including  selected from the group consisting of COX-2 inhibitors, anti-neoplastic agents, contraceptives, CNS active drugs, hormones, and vaccines. 
     
     
       18. The construct according to any one of claims  1 ,  2   or  3 , wherein the construct comprises an enzyme capable of hydrolytically cleaving the PEA polymer. 
     
     
       19. The construct according to  claim 18 , wherein the enzyme is α-chymotrypsin. 
     
     
       20. The construct according to  claim 18 , wherein the enzyme is adsorbed on the surface of the construct. 
     
     
       21. The construct according to  claim 18 , wherein the construct contains a bacteriophage which are  is released by action of the enzyme. 
     
     
       22. The construct according to  claim 1  wherein the blend is formed into a bioerodable coating on a support material or is formed into a bioerodable film. 
     
     
       23. The construct according to  claim 22  wherein the blend is formed into a bioerodable coating comprising bioactive material. 
     
     
       24. The construct according to  claim 1  wherein the construct is a device that can be surgically implanted. 
     
     
       25. The construct according to  claim 24  wherein the implantable device is an indwelling catheter or appliance for oral hygiene. 
     
     
       26. A bioerodable construct for controlled release of bioactive materials, said construct comprising a blend of at least two poly(ester-amide) polymers (PEA), wherein each PEA polymer has the formula: 
                   wherein 
 k= 2 - 12 ,  
 m= 2 - 12 , and  
 R=CH(CH 3   )   2   , CH   2   CH   (CH   3   )   2   , CH(CH   3   )CH   2   CH   3   , (CH   2   )   3   CH   3   , CH   2   C   6   H   5   , or (CH   2   )   2   SCH   3   ,    
   wherein the blend comprises a PEA polymer wherein R=CH 2   CH   (CH   3   )   2    or a PEA polymer wherein R=CH   2   C   6   H   5 .    
     
     
       27. The construct according to  claim 26 , wherein the blend comprises a first PEA polymer wherein R=CH 2   CH(CH   3   )   2   , and a second PEA polymer wherein R=CH   2   C   6   H   5 . 
     
     
       28. The construct of  claim 27 , wherein the first PEA polymer and second PEA polymer are present in a ratio of  10 : 1  to  1 : 1 . 
     
     
       29. The construct of  claim 28 , wherein the ratio of first PEA polymer to second PEA polymer is  5 : 1  to  2 . 5 : 1 . 
     
     
       30. The construct of  claim 26 , wherein k= 2 ,  3 ,  4 , or  6  and m= 4  or  8 . 
     
     
       31. The construct according to  claim 26 , wherein the construct is deformable sheet adapted to conform to a biological surface. 
     
     
       32. The construct according to  claim 31 , further comprising a bioactive agent. 
     
     
       33. The construct of  claim 32 , wherein the bioactive agent is selected from the group consisting of antiseptics, anti-infectives, bacteriophages, antibiotics, antibacterials, antiprotozoal agents, and antiviral agents, analgesics, anti-inflammatory agents selected from the group consisting of steroids and non-steroidal anti-inflammatory agents selected from the group consisting of COX- 2  inhibitors, anti-neoplastic agents, contraceptives, CNS active drugs, hormones, and vaccines. 
     
     
       34. The construct according to  claim 32 , wherein the construct comprises an enzyme capable of hydrolytically cleaving the PEA polymer. 
     
     
       35. The construct according to  claim 34 , wherein the enzyme is α-chymotrypsin. 
     
     
       36. The construct according to  claim 34 , wherein the enzyme is adsorbed on the surface of the construct. 
     
     
       37. The construct according to  claim 34 , wherein the construct contains a bacteriophage which is released by action of the enzyme. 
     
     
       38. A method of treating a patient having an ulcerative wound comprising inserting into the wound or covering the wound with a bioerodable construct according to  claim 26 , wherein the bioerodable construct is a deformable sheet containing a bioactive agent. 
     
     
       39. The method of  claim 38 , wherein the bioactive agent comprises a bacteriophage, an antibiotic, an antiseptic, or an analgesic. 
     
     
       40. The method of  claim 38 , wherein the wound is open or infected. 
     
     
       41. The method according to  claim 39 , wherein the bacteriophage is specific for bacteria found in the wound. 
     
     
       42. The method of  claim 38 , wherein the construct also comprises an enzyme capable of hydrolytically cleaving the PEA polymer. 
     
     
       43. The construct according to  claim 26  further comprising a bioactive agent. 
     
     
       44. The construct of  claim 43 , wherein the bioactive agent is selected from the group consisting of antiseptics, anti-infectives, bacteriophages, antibiotics, antibacterials, antiprotozoal agents, and antiviral agents, analgesics, anti-inflammatory agents selected from the group consisting of steroids and non-steroidal anti-inflammatory agents selected from the group consisting of COX- 2  inhibitors, anti-neoplastic agents, contraceptives, CNS active drugs, hormones, and vaccines. 
     
     
       45. The construct according to  claim 26 , wherein the construct comprises an enzyme capable of hydrolytically cleaving the PEA polymer. 
     
     
       46. The construct according to  claim 45 , wherein the enzyme is α-chymotrypsin. 
     
     
       47. The construct according to  claim 45 , wherein the enzyme is adsorbed on the surface of the construct. 
     
     
       48. The construct according to  claim 45 , wherein the construct contains a bacteriophage which is released by action of the enzyme. 
     
     
       49. The construct according to  claim 26  wherein the blend is formed into a bioerodable coating on a support material or is formed into a bioerodable film. 
     
     
       50. The construct according to  claim 49  wherein the blend is formed into a bioerodable coating comprising bioactive material. 
     
     
       51. The construct according to  claim 26  wherein the construct is a device that can be surgically implanted. 
     
     
       52. The construct according to  claim 51  wherein the implantable device is an indwelling catheter or appliance for oral hygiene. 
     
     
       53. A bioerodable construct for controlled release of bioactive materials, said construct comprising a blend of at least two poly(ester-amide) polymers (PEA) prepared by polymerizing a diol (D), wherein the diol (D) is not bisphenol; a dicarboxylic acid (C), wherein the dicarboxylic acid (C) is not phthalic acid; and an alpha-amino acid (A) through ester and amide links in the form (DACA) n   , wherein the alpha-amino acid (A) of each PEA polymer of the blend is selected from the group of amino acids having aliphatic side chains, amino acids having sulfur-containing side chains, and amino acids having side chains containing aromatic rings, and wherein the alpha-amino acid of at least one of the PEA polymers is phenylalanine or leucine.   
     
     
       54. The construct of  claim 53  wherein the amino acid having aliphatic side chains is selected from valine, leucine, isoleucine, and norleucine. 
     
     
       55. The construct of  claim 53 , wherein the amino acid having sulfur-containing side chains is methionine. 
     
     
       56. The construct of  claim 53 , wherein the amino acid having side chains containing aromatic rings is phenylalanine. 
     
     
       57. The construct of  claim 53  the blend comprises a first PEA polymer in which A is phenylalanine and a second PEA polymer in which A is leucine. 
     
     
       58. A bioerodable construct for controlled release of bioactive materials, said construct comprising a blend of at least two poly(ester-amide) polymers (PEA), wherein each PEA polymer has the formula: 
                   wherein 
 k= 2 - 12 ,  
 m= 2 - 12 ,  
   wherein R represents an amino acid side chain, and the amino acid side chain is selected from aliphatic side chains, sulfur-containing side chains, and side chains containing aromatic rings, and    wherein the blend comprises a PEA polymer wherein R is an amino acid side chain containing an aromatic ring or a PEA polymer wherein R is an aliphatic amino acid side chain.   
     
     
       59. The construct of  claim 58  wherein the aliphatic amino acid side chain is selected from valine, leucine, isoleucine, and norleucine side chains. 
     
     
       60. The construct of  claim 58 , wherein the sulfur-containing side chain is a methionine side chain. 
     
     
       61. The construct of  claim 58 , wherein the side chain containing aromatic rings is a phenylalanine side chain. 
     
     
       62. The construct of  claim 58  the blend comprises a first PEA polymer in which R is a phenylalanine side chain, and a second PEA polymer in which R is a leucine side chain. 
     
     
       63. The construct according to  claim 1  wherein the construct is a device for wound packing. 
     
     
       64. The construct according to  claim 63  wherein the construct is a foam. 
     
     
       65. The construct according to  claim 53  wherein the construct is a device for wound packing. 
     
     
       66. The construct according to  claim 65  wherein the construct is a foam.

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