US2007202178A1PendingUtilityA1

Drug delivery matrices to enhance wound healing

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Assignee: UNIV ZUERICHPriority: Apr 25, 2001Filed: Apr 24, 2007Published: Aug 30, 2007
Est. expiryApr 25, 2021(expired)· nominal 20-yr term from priority
Inventors:Jason SchenseHugo SchmoekelJeffrey A. HubbellFranz Weber
A61L 27/225A61L 24/0015A61L 2300/236A61L 2300/414A61L 2300/252A61L 2300/45A61P 19/00A61L 24/106A61P 17/02A61P 17/00A61L 27/227A61P 19/08A61L 31/046A61L 27/54A61L 2300/412
57
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Claims

Abstract

Bioactive molecules are entrapped within a matrix for the controlled delivery of these compounds for therapeutic healing applications. The matrix may be formed of natural or synthetic compounds. The primary method of entrapment of the bioactive molecule is through precipitation of the bioactive molecule during gelation of the matrix, either in vitro or in vivo. The bioactive molecule may be modified to reduce its effective solubility in the matrix to retain it more effectively within the matrix, such as through the deglycosylation of members within the cystine knot growth factor superfamily and particularly within the TGFβ superfamily. The matrix may be modified to include sites with binding affinity for different bioactive molecules, for example, for heparin binding.

Claims

exact text as granted — not AI-modified
1 . A composition for wound healing comprising: 
 a polymeric matrix consisting of fibrin or formed from synthetic polymers, and    a bioactive molecule, wherein the bioactive molecule is a deglycosylated member of the TGFβ superfamily,    and wherein the molecule is physically entrapped in the polymeric matrix.    
   
   
       2 . (canceled)  
   
   
       3 . The composition of  claim 1 , wherein the bioactive molecule is a deglycosylated bone morphogenetic protein.  
   
   
       4 . (canceled)  
   
   
       5 . The composition of  claim 1 , wherein the synthetic polymers are selected from the group consisting of poly(ethylene oxide) (PEO), poly(ethylene glycol) (PEG) and copolymers with poly(propylene) oxide (PEG-co-PPG), poly(vinyl alcohol) (PVA), poly(vinylpyrrolidone) (PVP), poly(ethyloxazoline) (PEOX), polyaminoacids, and pseudopolyamino acids, and copolymers of these polymers.  
   
   
       6 . (canceled)  
   
   
       7 . (canceled)  
   
   
       8 . The composition of  claim 1 , wherein the matrix is fibrin and the bioactive molecule is rh-BMP-2.  
   
   
       9 . (canceled)  
   
   
       10 . (canceled)  
   
   
       11 . (canceled)  
   
   
       12 . (canceled)  
   
   
       13 . (canceled)  
   
   
       14 . (canceled)  
   
   
       15 . A kit for wound healing comprising at least a first and a second composition separated from each other, wherein the first composition comprises a first three dimensional network precursor component, the second composition comprises a second three dimensional network precursor component, 
 wherein the precursor components form a three dimensional synthetic network or form a three dimensional fibrin network upon mixing under conditions that allow polymerization of the precursor components, and    wherein at least one of the first or second composition comprises a bioactive molecule wherein the bioactive molecule is a deglycosylated member of the TGFβ superfamily.    
   
   
       16 . The kit of  claim 15  wherein the first composition comprises fibrinogen.  
   
   
       17 . The kit of  claim 15  wherein the second composition comprises thrombin.  
   
   
       18 . (canceled)  
   
   
       19 . The kit of  claim 15  wherein at least one of the first or second composition further comprises a calcium source.  
   
   
       20 . The kit of  claim 15  wherein the first composition comprises fibrinogen and thrombin and the second composition comprises a calcium source.  
   
   
       21 . The kit of  claim 15  wherein the first composition comprises at least one component having n nucleophilic groups wherein n is at least two, 
 and the second composition comprises at least one component having m conjugated unsaturated groups wherein m is at least two,    and wherein the sum of n and m is at least five.    
   
   
       22 . The kit of  claim 21  wherein the nucleophilic groups and the conjugated unsaturated groups are capable of reacting with each other in a base catalysed Michael-type addition reaction.  
   
   
       23 . The kit of  claim 22  wherein the nucleophilic group is a thiol.  
   
   
       24 . The kit of  claim 22  wherein the conjugated unsaturated group is selected from the group consisting of vinylsulfone and acrylate.  
   
   
       25 . The kit of  claim 23  wherein the component comprising the thiol group is selected from the group consisting of polyethylene glycol, enzymatically degradable peptides and enzymatically degradable proteins.  
   
   
       26 . The kit of  claim 24  wherein the component comprising the conjugated unsaturated group is a synthetic polymer.  
   
   
       27 . The kit of  claim 21  wherein at least one of the first and second compositions further comprises a base.  
   
   
       28 . The kit of  claim 15  wherein the first composition comprises at least one component having n nucleophilic groups wherein n is at least two, 
 and at least one component having m conjugated unsaturated groups wherein m is at least two,    and wherein the sum on m and n is at least five,    and wherein the second composition comprises at least one base.    
   
   
       29 . The kit of  claim 28  wherein the nucleophilic groups and the conjugated unsaturated groups are capable of reacting with each other in a base catalyzed Michael-type addition reaction.  
   
   
       30 . The kit of  claim 29  wherein the nucleophilic group is a thiol.  
   
   
       31 . The kit of  claim 29  wherein the conjugated unsaturated group is selected from the group consisting of vinylsulfone and acrylate.  
   
   
       32 . The kit of  claim 30  wherein the component comprising the thiol groups is selected from the group consisting of polyethylene glycol, enzymatically degradable peptides and enzymatically degradable proteins.  
   
   
       33 . The kit of  claim 31  wherein the component comprising the conjugated unsaturated group is a synthetic polymer.  
   
   
       34 . (canceled)  
   
   
       35 . The kit of  claim 15  wherein the bioactive molecule is a deglycosylated bone morphogenetic protein.  
   
   
       36 . The kit of  claim 35  wherein the bioactive molecule is deglycosylated rh-BMP-2.  
   
   
       37 . (canceled)  
   
   
       38 . The kit of  claim 15  wherein the kit is in the from of a two compartment syringe wherein the first compartment comprises the first composition and the second compartment comprises the second composition and the two compartments are combined by a two way connector.  
   
   
       39 . (canceled)  
   
   
       40 . (canceled)  
   
   
       41 . (canceled)  
   
   
       42 . (canceled)  
   
   
       43 . (canceled)  
   
   
       44 . The kit of  claim 15 , wherein the conditions under which the components form a three dimensional matrix are physiological conditions in the human or animal body.  
   
   
       45 . The kit of  claim 38  wherein the two compartments are bipartite and separated by an adjustable partition perpendicular to the compartment wall.  
   
   
       46 . The composition of  claim 1 , wherein the synthetic polymers are functionalized such that they react in a Michael type addition reaction.  
   
   
       47 . The composition of  claim 1 , wherein the synthetic polymers are polyalkylene oxides.  
   
   
       48 . The kit of  claim 26 , wherein the synthetic polymers are polyalkylene oxides.

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