Methods of generating and using procollagen

Abstract

A method of promoting wound healing, treating fibrosis and/or promoting angiogenesis is provided. The method comprises administering to a subject in need thereof a therapeutically effective amount of a procollagen, thereby promoting wound healing, treating fibrosis and/or promoting angiogenesis in the subject.

What is claimed is: 
     
         1 . A method of promoting wound healing comprising administering to a subject in need thereof a therapeutically effective amount of a human type I procollagen and an antimicrobial agent, thereby promoting wound healing. 
     
     
         2 . The method of  claim 1 , wherein the α1 chain of said procollagen comprises the collagen N propeptide having the sequence of the N propeptide of collagen type I α1 chain as set forth in SEQ ID NO: 15 and wherein the α2 chain of said procollagen comprises the collagen N propeptide having the sequence of the N propeptide of collagen type I α2 chain as set forth in SEQ ID NO: 16; wherein the α1 chain of said procollagen comprises the collagen C propeptide having the sequence of the C propeptide of said collagen type I α1 chain and wherein the α2 chain of said procollagen comprises the collagen C propeptide having the sequence of the C propeptide of said collagen type I α2 chain. 
     
     
         3 . The method of  claim 1 , wherein said administering is effected into a tissue area which comprises said wound. 
     
     
         4 . The method of  claim 1 , wherein said administering is effected prior to fibroblast recruitment to the wound. 
     
     
         5 . The method of  claim 1 , wherein said procollagen is produced in plant cells. 
     
     
         6 . The method of  claim 1 , wherein said procollagen is degradable by collagenase. 
     
     
         7 . The method of  claim 1 , wherein said wound is related to a fibrotic condition selected from the group consisting of systemic or localized scleroderma, liver fibrosis, alcoholic cirrhosis, biliary cirrhosis, hepatitis, veno-occlusive disease, idiopathic interstitial fibrosis, idiopathic pulmonary fibrosis, interstitial pulmonary fibrosis, acute pulmonary fibrosis, acute respiratory distress syndrome, perimuscular fibrosis, pericentral fibrosis, dermatofibroma, kidney fibrosis, diabetic nephropathy, glomerulonephritis, keloids, hypertrophic scars, joint adhesions, arthrosis, myelofibrosis, corneal scaring, cystic fibrosis, muscular fibrosis, Duchenne's muscular dystrophy, esophageal stricture, retroabdominal scaring, Crohn's disease, ulcerative colitis, atherosclerotic alterations, pulmonary hypertension, angiopathy of the arteries and veins, aneurysms of large vessels or are induced or initiated by scar revisions, plastic surgeries, glaucoma, cataract fibrosis, corneal scaring, graft vs. host disease, tendon surgery, nerve entrapment, Dupuytren's contracture, OB/GYN adhesions, pelvic adhesions, peridural fibrosis, diseases of the thyroid gland or the parathyroids, metastatic bone disease, multiple myeloma and restenosis. 
     
     
         8 . The method  claim 1 , wherein said wound is inflicted by diabetes. 
     
     
         9 . The method  claim 1 , wherein said wound is selected from the group consisting of an ulcer, a burn and a surgical wound. 
     
     
         10 . The method of  claim 1 , wherein said wound is a surgical wound. 
     
     
         11 . The method of  claim 1 , wherein said procollagen comprises monomeric procollagen. 
     
     
         12 . The method of  claim 1 , wherein said antimicrobial agent is formulated together with said procollagen. 
     
     
         13 . The method of  claim 1 , wherein said antimicrobial agent is selected from the group consisting of antibacterial agents, anti-yeast agents, anti-fungal agents, antiviral agents, and anti-protozal agents. 
     
     
         14 . The method of  claim 1 , wherein said antibacterial agent is an antibiotic. 
     
     
         15 . An article of manufacture comprising a packaging material which packages as active ingredients human procollagen and an antimicrobial agent. 
     
     
         16 . The article of manufacture of  claim 15 , wherein said human procollagen and said antimicrobial agent are packaged in the same packaging. 
     
     
         17 . The article of manufacture of  claim 15 , wherein said human procollagen and said antimicrobial agent are formulated in a single pharmaceutical composition. 
     
     
         18 . The article of manufacture of  claim 15 , wherein said human procollagen and said antimicrobial agent are packaged in separate packaging. 
     
     
         19 . The article of manufacture of  claim 15 , wherein the α1 chain of said procollagen comprises the collagen N propeptide having the sequence of the N propeptide of collagen type I al chain as set forth in SEQ ID NO: 15 and wherein the α2 chain of said procollagen comprises the collagen N propeptide having the sequence of the N propeptide of collagen type I α2 chain as set forth in SEQ ID NO: 16; wherein the α1 chain of said procollagen comprises the collagen C propeptide having the sequence of the C propeptide of said collagen type I al chain and wherein the α2 chain of said procollagen comprises the collagen C propeptide having the sequence of the C propeptide of said collagen type I α2 chain. 
     
     
         20 . The article of manufacture of  claim 15 , wherein said antimicrobial agent is selected from the group consisting of antibacterial agents, anti-yeast agents, anti-fungal agents, antiviral agents, and anti-protozal agents. 
     
     
         21 . The article of manufacture of  claim 15 , wherein said antibacterial agent is an antibiotic.