Methods for treating wounds

Abstract

Novel compositions for treating wounds and promoting the healing thereof are described, including composition containing novel combinations of a carrier and recombinant platelet derived grown factor having fewer isoforms and enhanced biostability. Methods of treating wounds with novel therapeutic composition using dosing procedures leading to effective results with a minimal number of treatment applications are also described.

What is claimed is: 
     
         1 . A method of treating a wound, wherein said method comprises:
 (1) forming a therapeutic composition consisting essentially of sterile recombinant human PDGF-BB (rhPDGF-BB) in a physiologic solution and a sterile porous biocompatible carrier, wherein the porous biocompatible carrier is a polysaccharide, collagen, gelatin, fibrin, alginate, cellulose, or fibronectin, or combinations thereof, and said therapeutic composition is free from an enzyme inhibitor;   (2) applying the therapeutic composition to the wound surface in an amount that is at least about 10 μg rhPDGF-BB per cm 2  of treated wound surface area or in an amount that is from about 1.2 μg PDGF/cm 3  of carrier to about 12 mg PDGF/cm 3  of carrier, wherein the carrier provides a substrate for cell attachment and vascular ingrowth as the wound heals;   (3) monitoring the healing of the wound during a treatment period and repeating step (2) to retreat the wound at treatment intervals of 7 or more days,   (4) wherein the wound is retreated from 0 to 20 times, and wherein each retreatment comprises applying the therapeutic composition to the wound surface in an amount that is at least 10 μg rhPDGF-BB/cm 2  treated wound surface area up to 100 μg rhPDGF-BB/cm 2  treated wound surface area or in an amount that is from about 1.2 μg PDGF/cm 3  of carrier to about 12 mg PDGF/cm 3  of carrier.   
     
     
         2 . The method of  claim 1  wherein the wound is retreated from 1 to 8 times at least about every 30 days. 
     
     
         3 . The method of  claim 1  wherein the wound is a dermal wound, diabetic ulcer, venous stasis ulcers, pressure ulcers, burn, traumatic injury, acute wound, superficial wound, or surgical wound. 
     
     
         4 . The method of  claim 1 , wherein the method is applied to heal a wound following plastic or reconstructive surgery. 
     
     
         5 . The method of  claim 1 , wherein the method is applied to heal an injury that has been intentionally created to improve appearance or aesthetics in a human being. 
     
     
         6 . The method of  claim 1 , wherein the method is applied to enhance collagen production and tissue volume with the goal to improve function or appearance or aesthetic outcomes in a human being. 
     
     
         7 . The method of  claim 1  wherein carrier is a polysaccharide, the wound is a wound following plastic or reconstructive surgery, and the wound is retreated from 1 to 8 times at least about every 30 days. 
     
     
         8 . The method of  claim 1  wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:
 (i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB; and 
 (ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml/cm 3  carrier to about 1 ml/cm 3 . 
 
     
     
         9 . The method of  claim 1  wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:
 (i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and 
 (ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm 3  of carrier to about 10 ml solution/cm 3  of carrier, or the ratio of rhPDGF-BB to the carrier is between about 1.2 μg rhPDGF-BB/cm 3  of carrier to about 750 μg rhPDGF-BB/cm 3  of carrier. 
 
     
     
         10 . The method of  claim 1  wherein at least about 80% of the rhPDGF-BB on a weight basis is unclipped rhPDGF-BB. 
     
     
         11 . The method of  claim 1  wherein the porous biocompatible carrier is a polysaccharide. 
     
     
         12 . The method of  claim 1  wherein the porous biocompatible carrier is a gelatin. 
     
     
         13 . The method of  claim 1  wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB. 
     
     
         14 . The method of  claim 1  wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 25 mg of rhPDGF-BB. 
       The method of  claim 1  wherein the wound is retreated from 1 to 20 times over a maximum treatment period of 2 to 20 weeks. 
     
     
         15 . The method of  claim 1  wherein step (2) is repeated to retreat the wound at a retreatment frequency of at least every 8 days. 
     
     
         16 . The method of  claim 1  wherein step (2) is repeated to retreat the wound at a retreatment frequency of at least every 10 days. 
     
     
         17 . The method of  claim 1  wherein the wound is retreated a maximum of 10 times. 
     
     
         18 . The method of  claim 1  wherein:
 (A) the wound is a dermal wound, diabetic ulcer, venous stasis ulcers, pressure ulcers, burn, traumatic injury, acute wound, superficial wound, or surgical wound, or the method is applied to heal a wound following plastic or reconstructive surgery; 
 (B) the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:
 (i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, wherein at least about 80% of the rhPDGF-BB on a weight basis is unclipped rhPDGF-BB, and 
 (ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm 3  of carrier to about 1 ml solution/cm 3  of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μg rhPDGF-BB/cm 3  of carrier to about 225 μg rhPDGF-BB/cm 3  of carrier; 
 
 (C) the wound is retreated from 2 to 20 times over a maximum treatment period of 2 to 20 weeks at a retreatment frequency of at least every 8 days; and 
 (D) the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB. 
 
     
     
         19 . The method of  claim 1  wherein the method further includes the initial step of debriding the wound to remove necrotic or infected tissue. 
     
     
         20 . The method of  claim 1  further comprising the step of covering the wound with a dressing following the application of the therapeutic composition. 
     
     
         21 . A method of treating a wound, wherein said method comprises:
 (1) forming a therapeutic composition consisting essentially of sterile recombinant human PDGF-BB (rhPDGF-BB) in a physiologic solution and a sterile porous biocompatible carrier, wherein the porous biocompatible carrier is a polysaccharide, collagen, gelatin, fibrin, alginate, cellulose, or fibronectin;   (2) applying the therapeutic composition to the wound surface in an amount that is at least about 10 μg rhPDGF-BB per cm 2  of treated wound surface area or in an amount that is from about 1.2 μg PDGF/cm 3  of carrier to about 12 mg PDGF/cm 3  of carrier, wherein the carrier provides a substrate for cell attachment and vascular ingrowth as the wound heals;   (4) covering the wound with a dressing; and   (5) monitoring the healing of the wound during a treatment period and repeating step (2) to retreat the wound at treatment intervals of 3 to 42 days;   wherein the wound is retreated from 2 to 20 times, and wherein each retreatment comprises applying the therapeutic composition to the wound surface in an amount that is at least 10 μg rhPDGF-BB/cm 2  treated wound surface area up to 100 μg rhPDGF-BB/cm 2  treated wound surface area or in an amount that is from about 1.2 μg PDGF/cm 3  of carrier to about 12 mg PDGF/cm 3  of carrier.   
     
     
         22 . The method of  claim 21  wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:
 (i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and 
 (ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm 3  of carrier to about 1 ml solution/cm 3  of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μg rhPDGF-BB/cm 3  of carrier to about 225 μg rhPDGF-BB/cm 3  of carrier. 
 
     
     
         23 . The method of  claim 21  wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:
 (i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and 
 (ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.25 ml solution/cm 3  of carrier to about 5 ml solution/cm 3  of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μg rhPDGF-BB/cm 3  of carrier to about 750 μg rhPDGF-BB/cm 3  of carrier. 
 
     
     
         24 . The method of  claim 21  wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB. 
     
     
         25 . The method of  claim 21  wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 25 mg of rhPDGF-BB. 
     
     
         26 . The method of  claim 21  wherein step 2 is repeated to retreat the wound at a retreatment frequency of at least every 10 days. 
     
     
         27 . The method of  claim 21  wherein the wound is retreated a maximum of 10 times. 
     
     
         28 . The method of  claim 21  wherein:
 (A) the wound is a dermal wound, diabetic ulcer, venous stasis ulcers, pressure ulcers, burn, traumatic injury, acute wound, superficial wound, or surgical wound, or the method is applied to heal a wound following plastic or reconstructive surgery; 
 (B) the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:
 (i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, wherein at least about 80% of the rhPDGF-BB on a weight basis is unclipped rhPDGF-BB, and 
 (ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm 3  of carrier to about 1 ml solution/cm 3  of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μg rhPDGF-BB/cm 3  of carrier to about 225 μg rhPDGF-BB/cm 3  of carrier; and 
 
 (C) the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB. 
 
     
     
         29 . A method of treating a wound, wherein said method comprises:
 (1) debriding the wound to remove necrotic or infected tissue, if present;   (2) forming a therapeutic composition consisting essentially of sterile recombinant human PDGF-BB (rhPDGF-BB) in a physiologic solution and a sterile porous biocompatible carrier, wherein the porous biocompatible carrier is a polysaccharide, collagen, gelatin, fibrin, alginate, cellulose, or fibronectin;   (3) applying the therapeutic composition to the wound surface in an amount that is at least about 10 μg rhPDGF-BB per cm 2  of treated wound surface area or in an amount that is from about 1.2 μg PDGF/cm 3  of carrier to about 12 mg PDGF/cm 3  of carrier, wherein the carrier provides a substrate for cell attachment and vascular ingrowth as the wound heals;   (4) covering the wound with a dressing; and   (5) monitoring the healing of the wound during a treatment period and repeating steps (1)-(4) to retreat the wound at treatment intervals of 10 or more days,   wherein the wound is retreated from 2 to 20 times, and wherein each retreatment comprises applying the therapeutic composition to the wound surface in an amount that is at least 10 μg rhPDGF-BB/cm 2  treated wound surface area up to 100 μg rhPDGF-BB/cm 2  treated wound surface area or in an amount that is from about 1.2 μg PDGF/cm 3  of carrier to about 12 mg PDGF/cm 3  of carrier.   
     
     
         30 . The method of  claim 29  wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:
 (i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and 
 (ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm 3  of carrier to about 1 ml solution/cm 3  of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μg rhPDGF-BB/cm 3  of carrier to about 225 μg rhPDGF-BB/cm 3  of carrier. 
 
     
     
         31 . The method of  claim 29  wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:
 (i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and 
 (ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.25 ml solution/cm 3  of carrier to about 5 ml solution/cm 3  of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μg rhPDGF-BB/cm 3  of carrier to about 750 μg rhPDGF-BB/cm 3  of carrier. 
 
     
     
         32 . The method of  claim 29  wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB. 
     
     
         33 . The method of  claim 29  wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 25 mg of rhPDGF-BB. 
     
     
         34 . The method of  claim 29  wherein the wound is retreated from 2 to 20 times over a maximum treatment period of 2 to 20 weeks. 
     
     
         35 . The method of  claim 1  wherein when the rhPDGF-BB and the porous carrier are combined, the carrier is capable of entrapping the rhPDGF-BB within its pores such that the rhPDGF-BB is released over time as the carrier is absorbed by the patient's body, thereby providing controlled delivery of rhPDGF-BB at the wound over an extended period of time and simultaneously providing a matrix for new cell and tissue ingrowth.