Histatin for Corneal Wound Healing and Ocular Surface Disease

Abstract

Histatins may be used for corneal wound healing and as a treatment for ocular surface disease in humans and other animals. For example, histatins could be included in eye drops, eye gels, ointment, glue, or embedded in (polymer) contact lenses.

What is claimed is: 
     
         1 . A method of treating corneal wounds, comprising the step of administering a therapeutic amount of at least a peptide fragment of at least one histatin at a site of a corneal wound. 
     
     
         2 . The method of  claim 1 , wherein the histatin is administered using eye drops, gels, or ointments including histatin. 
     
     
         3 . The method of  claim 1 , wherein the histatin is administered using tissue glue. 
     
     
         4 . The method of  claim 1 , wherein the histatin is continually administered by incorporating histatin into a contact lens worn by a patient. 
     
     
         5 . The method of  claim 1 , wherein humans are treated by the method. 
     
     
         6 . The method of  claim 1 , wherein a histatin concentration is between approximately 0.1 μg/ml and approximately 1000 mg/ml. 
     
     
         7 . The method of  claim 6 , wherein a histatin concentration is between approximately 0.1 μg/ml and 10 μg/ml. 
     
     
         8 . The method of  claim 1 , wherein the step is repeated at least one time a day for a plurality of days. 
     
     
         9 . The method of  claim 1 , wherein the step is repeated chronically at least one time a day. 
     
     
         10 . The method of  claim 1 , wherein the step is repeated up to hourly for a plurality of days. 
     
     
         11 . The method of  claim 1 , wherein the step is repeated at least two times a day for a plurality of days. 
     
     
         12 . The method of  claim 1 , wherein the step is repeated at least three times a day for a plurality of days. 
     
     
         13 . The method of  claim 1 , wherein the step is repeated three times a day for seven days. 
     
     
         14 . The method of  claim 1 , wherein the step is repeated four times a day for five days. 
     
     
         15 . The method of  claim 1 , wherein the therapeutic amount of histatin accelerates wound healing compared to corneal wounds not treated with histatin. 
     
     
         16 . The method of  claim 1 , wherein the histatin comprises an amino acid sequence selected from the group consisting of: SEQ. ID. NO. 1; SEQ. ID. NO. 2; SEQ. ID. NO. 3; SEQ. ID. NO. 4; SEQ. ID. NO. 5; SEQ. ID. NO. 6; SEQ. ID. NO. 7; SEQ. ID. NO. 8; SEQ. ID. NO. 9; SEQ. ID. NO. 10; SEQ. ID. NO. 11; SEQ. ID. NO. 12; SEQ. ID. NO. 13; SEQ. ID. NO. 14; SEQ. ID. NO. 15; SEQ. ID. NO. 16; SEQ. ID. NO. 17; SEQ. ID. NO. 18; SEQ. ID. NO. 19; SEQ. ID. NO. 20; SEQ. ID. NO. 21; SEQ. ID. NO. 22; SEQ. ID. NO. 23; SEQ. ID. NO. 24; SEQ. ID. NO. 25; SEQ. ID. NO. 26; SEQ. ID. NO. 27; SEQ. ID. NO. 28; SEQ. ID. NO. 29; SEQ. ID. NO. 30; SEQ. ID. NO. 31; SEQ. ID. NO. 32; SEQ. ID. NO. 33; and any combination of SEQ. ID. NO. 1 through SEQ. ID. NO. 33. 
     
     
         17 . The method according to  claim 1 , wherein the histatin comprises a peptide comprising 8 to 44 amino acids. 
     
     
         18 . The method according to  claim 1 , wherein the histatin includes an L peptide. 
     
     
         19 . The method according to  claim 1 , wherein the histatin includes a cyclic peptide. 
     
     
         20 . The method of  claim 1 , wherein the histatin is selected from the group consisting of:
 a) at least a peptide fragment of histatin 1;   b) at least a peptide fragment of histatin 2;   c) at least a peptide fragment of histatin 5; and   d) any combination of a) through c).   
     
     
         21 . The method of  claim 1 , wherein the histatin comprises:
 a) at least a peptide fragment of histatin 1, at least a peptide fragment of histatin 2 or a combination of at least a peptide fragment of histatin 1 and at least a peptide fragment of histatin 2; and   b) at least a peptide fragment of histatin 5.   
     
     
         22 . The method of  claim 21 , wherein the peptide fragment of histatin 5 is selected from the group consisting of SEQ. ID. NO. 30 and SEQ. ID. NO. 31. 
     
     
         23 . The method of  claim 21 , wherein the peptide fragments of histatin 1 or histatin 2 are selected from the group consisting of SEQ. ID. NO. 4; SEQ. ID. NO. 5; SEQ. ID. NO. 8; SEQ. ID. NO. 9; SEQ. ID. NO. 13; SEQ. ID. NO. 29; and SEQ. ID. NO. 
     
     
         24 . The method of  claim 1 , wherein the histatin is selected from the group consisting of:
 a) histatin 1;   b) histatin 2;   c) histatin 5; and   d) any combination of a) through c).   
     
     
         25 . The method of  claim 1 , wherein the histatin comprises:
 a) histatin 1, histatin 2 or a combination of histatin 1 and histatin 2; and   b) histatin 5.   
     
     
         26 . The method of  claim 25 , wherein the histatin comprises an amino acid sequence of histatin 5 selected from the group consisting of SEQ. ID. NO. 30 and SEQ. ID. NO. 31. 
     
     
         27 . The method of  claim 25 , wherein the histatin comprises an amino acid sequence of histatin 1 or histatin 2 selected from the group consisting of SEQ. ID. NO. 4; SEQ. ID. NO. 5; SEQ. ID. NO. 8; SEQ. ID. NO. 9; SEQ. ID. NO. 13; SEQ. ID. NO. 29;
 and SEQ. ID. NO. 33.   
     
     
         28 . The method of  claim 1 , wherein the histatin comprises at least a first histatin and a second histatin, wherein:
 a) the first histatin is selected from the group consisting of: i) at least a peptide fragment of histatin 1 and ii) at least a peptide fragment of histatin 2; and   b) the second histatin comprises at least a peptide fragment of histatin 5.   
     
     
         29 . The method of  claim 28 , wherein the second histatin comprises an amino acid sequence selected from the group consisting of SEQ. ID. NO. 30 and SEQ. ID. NO. 31. 
     
     
         30 . The method of  claim 28 , wherein the first histatin comprises an amino acid sequence selected from the group consisting of SEQ. ID. NO. 4; SEQ. ID. NO. 5; SEQ. ID. NO. 8; SEQ. ID. NO. 9; SEQ. ID. NO. 13; SEQ. ID. NO. 29; and SEQ. ID. NO.  33 .