Histatin for Corneal Wound Healing and Ocular Surface Disease
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.
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 .