Impaired wound healing composition and treatments

Abstract

Connexin modulation for the treatment of wounds that do not heal at expected rates, including delayed healing wounds, incompletely healing wounds, and chronic wounds, and associated methods, compositions and articles.

1 . A method of treating a subject having a wound not healing at an expected rate, which comprises administration of an effective amount of an anticonnexin 43 polynucleotide to the wound. 
     
     
         2 . A method according to  claim 1  wherein the anticonnexin 43 polynucleotide is a connexin 43 antisense polynucleotide. 
     
     
         3 . A method according to  claim 1  wherein the anticonnexin 43 polynucleotide is a RNAi polynucleotide. 
     
     
         4 . A method according to  claim 1  wherein the anticonnexin 43 polynucleotide is a siRNA polynucleotide. 
     
     
         5 . A method according to  claim 1  wherein the anticonnexin 43 polynucleotide is administered for at least about 0.5 hours, at least about 1-2 hours, at least about 2-4 hours, at least about 4-6 hours, or at least about 6-8 hours. 
     
     
         6 . A method according to  claim 1  wherein the wound is a dehiscent wound. 
     
     
         7 . A method according to  claim 1  wherein the wound is a delayed or incompletely healing wound. 
     
     
         8 . A method according to  claim 1  wherein the wound is a chronic wound. 
     
     
         9 . A method according to  claim 1  wherein the wound is a vasculitic ulcer. 
     
     
         10 . A method according to  claim 1  wherein the wound is a venous ulcer or a venous stasis ulcer. 
     
     
         11 . A method according to  claim 1  wherein the wound is an arterial ulcer. 
     
     
         12 . A method according to  claim 1  wherein the wound is a pressure ulcer or a decubitus ucler. 
     
     
         13 . A method according to  claim 1  wherein the wound is a diabetic ulcer. 
     
     
         14 . A method according to  claim 1  wherein the wound is a skin ulcer resulting from trauma. 
     
     
         15 . A method according to  claim 1  wherein the wound is a skin ulcer resulting from a burn. 
     
     
         16 . A method according to  claim 1  wherein the subject is diabetic. 
     
     
         17 . A method according to  claim 1  wherein the subject is a human. 
     
     
         18 . A method according to  claim 1  wherein the subject is a non-human animal. 
     
     
         19 . A method according to  claim 18  wherein the animal is a horse. 
     
     
         20 . A method according to  claim 18  wherein the animal is a dog. 
     
     
         21 . A method according to  claim 18  wherein the animal is a cat. 
     
     
         22 . A method according to  claim 1 , wherein the anti-connexin 43 polynucleotide is administered in an amount ranging from about 1 to about 100 μg per square centimeter of wound size. 
     
     
         23 . A method according to  claim 22  wherein the administration of said anti-connexin 43 polynucleotide is repeated. 
     
     
         24 . A method according to  claim 22  wherein the administration of said anti-connexin 43 polynucleotide is repeated about once per week, whereby wound healing is promoted. 
     
     
         25 . A method of treating a subject having a delayed healing, incompletely healing, or chronic wound which comprises administration to the wound of a connexin 43 antisense polynucleotide whereby connexin 43 expression is downregulated over a sustained period of time. 
     
     
         26 . A method according to  claim 25  wherein connexin 43 expression is downregulated for at least about 0.5 hours, at least about 1-2 hours, at least about 2-4 hours, at least about 4-6 hours, or at least about 6-8 hours. 
     
     
         27 . A method of treating a subject having a delayed healing, incomplete healing or chronic wound which comprises administration to a wound area of a connexin 43 antisense polynucleotide whereby connexin 43 levels in the wound area are decreased for at least about 0.5 hours, at least about 1-2 hours, at least about 2-4 hours, at least about 4-6 hours, or at least about 6-8 hours. 
     
     
         28 . A method of promoting wound healing in a subject having a delayed healing, incomplete healing or chronic wound which comprises administration to the wound of a therapeutically effective amount of a connexin 43 antisense polynucleotide effective to downregulate connexin 43 expression for a sustained period of time. 
     
     
         29 . A method according to  claim 28  wherein connexin 43 expression is downregulated for at least about 0.5 hours, at least about 1-2 hours, at least about 2-4 hours, at least about 4-6 hours, or at least about 6-8 hours. 
     
     
         30 . A method of promoting wound healing in a subject having a delayed healing or chronic wound which comprises administration of a therapeutically effective amount of a connexin 43 antisense polynucleotide to a wound area effective to increase re-epithelialization rates in the wound area. 
     
     
         31 . A method according to  claim 30  wherein the antisense polynucleotide is administered in a sustained release formulation. 
     
     
         32 . A method according to  claim 30  wherein the polynucleotide is administered for a sustained period of time. 
     
     
         33 . A method according to  claim 30  wherein the antisense polynucleotide is effective to decrease connexin 43 levels for at least about 0.5 hours, at least about 1-2 hours, at least about 2-4 hours, at least about 4-6 hours, or at least about 6-8 hours. 
     
     
         34 . A method of promoting re-epithelialization of skin wounds which comprises administering to a subject having a delayed healing, incomplete healing or chronic wound an anticonnexin 43 polynucleotide in an amount effective to promote re-epithelialization. 
     
     
         35 . A method according to  claim 34  wherein the anti-connexin 43 polynucleotide is a connexin 43 antisense polynucleotide. 
     
     
         36 . A method of promoting wound healing in a subject having a delayed healing, incomplete healing or chronic wound which comprises administration of a pharmaceutical composition comprising a connexin 43 antisense polynucleotide and a connexin 31.1 antisense polynucleotide. 
     
     
         37 . A method of increasing the rate of wound healing in a diabetic subject having a wound which comprises administering to the subject an effective amount of an anticonnexin 43 polynucleotide. 
     
     
         38 . A method according to  claim 37  wherein the anticonnexin 43 polynucleotide is a RNAi polynucleotide. 
     
     
         39 . A method according to  claim 37  wherein the anticonnexin 43 polynucleotide is a siRNA polynucleotide. 
     
     
         40 . A method according to  claim 37  wherein the anticonnexin 43 polynucleotide is a connexin 43 antisense polynucleotide. 
     
     
         41 . A method according to  claim 37  wherein said polynucleotide has from about 18 to about 32 nucleotides. 
     
     
         42 . A method according to  claim 41  wherein the polynucleotide is an oligodeoxynucleotide. 
     
     
         43 . A method of increasing rate of wound healing in a diabetic subject having a wound which comprises administering to the subject an amount of an anticonnexin 43 polynucleotide effective to decrease abnormal connexin 43 regulation in the wound or a wound area. 
     
     
         44 . A method according to  claim 43  wherein the anticonnexin 43 polynucleotide is a RNAi polynucleotide. 
     
     
         45 . A method according to  claim 43  wherein the anticonnexin 43 polynucleotide is a siRNA polynucleotide. 
     
     
         46 . A method according to  claim 43  wherein the anticonnexin 43 polynucleotide is a connexin 43 antisense polynucleotide. 
     
     
         47 . A method according to  claim 46  wherein the connexin 43 antisense polynucleotide is a connexin 43 oligodeoxynucleotide. 
     
     
         48 . A method according to  claim 46  wherein the polynucleotide has from about 18 to about 32 nucleotides. 
     
     
         49 . A method of improving wound closure in a diabetic subject having a wound which comprises administering to the subject an effective amount of an anticonnexin 43 polynucleotide. 
     
     
         50 . A method according to  claim 49  wherein the anticonnexin 43 polynucleotide is a RNAi polynucleotide. 
     
     
         51 . A method according to  claim 49  wherein the anticonnexin 43 polynucleotide is a siRNA polynucleotide. 
     
     
         52 . A method according to  claim 49  wherein the anticonnexin 43 polynucleotide is a connexin 43 antisense polynucleotide. 
     
     
         53 . A method according to  claim 49  wherein the connexin 43 antisense polynucleotide has from about 18 to about 32 nucleotides. 
     
     
         54 . A method according to  claim 49  wherein the polynucleotide is an oligodeoxynucleotide. 
     
     
         55 . A method according to any of  claims 1 ,  25 ,  27 ,  28 ,  30 ,  34 ,  36 ,  37 ,  43 , and  49  wherein the antisense polynucleotide comprises a sequence selected from SEQ.ID.NOS.:1 or 
     
     
         56 . A method according to any of  claims 1 ,  25 ,  27 ,  28 ,  30 ,  34 ,  36 ,  37 ,  43 , and  49  wherein the antisense polynucleotide has at least about 70 percent homology with SEQ.ID.NOS.:1 or 2. 
     
     
         57 . A method according to any of  claims 1 ,  25 ,  27 ,  28 ,  30 ,  34 ,  36 ,  37 ,  43 , and  49  wherein the connexin 43 antisense polynucleotide hybridizes to connexin 43 mRNA under conditions of medium to high stringency. 
     
     
         58 . A synthetic or naturally occurring wound healing matrix comprising an anti-connexin polynucleotide. 
     
     
         59 . A wound healing matrix of  claim 58 , wherein the anti-connexin polynucleotide is a connexin 43 antisense polynucleotide. 
     
     
         60 . A wound healing matrix of  claim 58 , wherein the anti-connexin polynucleotide is a oligodeoxynucleotide. 
     
     
         61 . A wound healing matrix of  claim 60 , wherein the anti-connexin oligodeoxynucleotide is a connexin 43 antisense oligodeoxynucleotide.