Compositions for prevention of adhesions and other barrier applications
A method has been developed of preventing or limiting formation of adhesions by administering to a site in need thereof, in the absence of or after bleeding or leakage of fluid has been substantially stopped, a self-assembling material which forms a barrier to formation of adhesions. In certain embodiments, the self assembling materials are peptidomimetics, nucleotidomimetics, di- and triblock copolymers, N-alkylacrylamides, or dendimers. These materials are also useful in a method for regeneration or repair of tissue or cells forming tissue.
1. A method of treating a patient at risk of forming adhesions at a wound or surgery site or a site of inflammation comprising:
administering to tissue at risk of forming adhesions an effective amount of a self-assembling material to reduce the formation of adhesions at the site of administration relative to an untreated control, wherein the self-assembling material comprises a concentration of ions of less than 5 mM and self-assembling peptides having a sequence of amino acids comprising one or more of Formulae MV:
((Xaa neu −Xaa + ) x (Xaa neu −Xaa − ) y ) n (I)
((Xaa neu −Xaa − ) x (Xaa neu −Xaa + ) y ) n (II)
((Xaa + −Xaa neu ) x (Xaa − -Xaa neu ) y ) n (III)
((Xaa − −Xaa neu ) x (Xaa + -Xaa nue ) y ) n (IV)
wherein: Xaa neu is an amino acid residue having a neutral charge; Xaa + is an amino acid residue having a positive charge; Xaa − is an amino acid residue having a negative charge; x and y are integers having a value of 1, 2 or 4, independently;
and n is an integer having a value of 1-5, and wherein the self-assembling material does not include cells.
2. The method of claim 1 , wherein Xaa neu is alanine, leucine or isoleucine; Xaa + is arginine or lysine; and Xaa − is aspartic acid or glutamic acid.
3. The method of claim 1 , wherein the amino acids include naturally occurring amino acid residues.
4. The method of claim 1 , wherein the amino acids are non-naturally occurring amino acid residues.
5. The method of claim 1 further comprising providing with the self assembling materials a pharmaceutically acceptable carrier or matrix or support material for administration onto or into the body.
6. The method of claim 5 wherein the materials are administered as a dry powder, wafer, disk, tablet, capsule, liquid, gel, cream, foam, ointment, emulsion, suspension, solution, as a coating on a medical device or implant, or incorporated into microparticles, polymeric matrices, hydrogels, textile, suture, or sponges.
7. The method of claim 6 , wherein the self-assembling materials are administered as a liquid containing about 0.1% inclusive to about 5% inclusive weight to volume of self-assembling peptides.
8. The method of claim 1 , wherein the self-assembling material is administered in an amount effective to reduce formation of adhesions at the site of administration for at least 8 weeks relative to an untreated control.