Compositions and methods for treating eye infections and disease
The present invention provides compositions and methods for identifying subjects suffering from dry eye that can be treated by topical administration of a composition comprising lacritin or a bioactive fragment thereof. The application discloses in part that a ˜90 KDa deglycanated form of syndecan-1 is abundant in tears of normal individuals but not individuals suffering from dry eye, whereas a ˜25 kDa syndecan-1 fragment is detectable in dry, but not normal tears.
1. A sterile, aqueous pharmaceutical composition for topical administration to an ocular surface, the composition comprising:
a peptide, or a pharmaceutically acceptable salt thereof,
wherein the peptide, or a pharmaceutically acceptable salt thereof, has an amino acid sequence consisting of SEQ ID NO: 5,
wherein the C-terminus of the peptide is amidated,
wherein the N-terminus of the peptide is acetylated, and a pharmaceutically acceptable aqueous carrier,
wherein the sterile, aqueous pharmaceutical composition is suitable for topical administration to an ocular surface of a subject, and
wherein the sterile, aqueous pharmaceutical composition is free of any type of enzymatic, chemical or biochemical molecule capable of breakdown of the peptide at its termini that is sequential degradation of the peptide at a terminal end thereof in the absence of the C-terminus amidation and the N-terminus acetylation.
2. The sterile, aqueous pharmaceutical composition of claim 1 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.001% to 1% (w/w).
3. The sterile, aqueous pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier comprises a buffer.
4. The sterile, aqueous pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a tonicity agent.
5. The sterile, aqueous pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a viscosity building agent.
6. The sterile, aqueous pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises one or more salts.
7. The sterile, aqueous pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a lubricating agent.
8. The sterile, aqueous pharmaceutical composition of claim 1 ,
wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.001% to 1% (w/w),
wherein the pharmaceutically acceptable aqueous carrier comprises a buffer, and
wherein the sterile, aqueous pharmaceutical composition further comprises,
a tonicity agent, and
a surfactant.
9. A method of treating dry eye, the method comprising:
topically administering a therapeutically effective amount of a sterile, aqueous, topical pharmaceutical composition to an ocular surface,
wherein the sterile aqueous topical pharmaceutical composition comprises:
a peptide, or a pharmaceutically acceptable salt thereof,
wherein the peptide, or pharmaceutically acceptable salt thereof, has an amino acid sequence consisting of SEQ ID NO: 5,
wherein the C-terminus of the peptide is amidated,
wherein the N-terminus of the peptide is acetylated, and
a pharmaceutically acceptable aqueous carrier,
wherein the sterile, aqueous pharmaceutical composition is suitable for topical administration to an ocular surface of a subject, and
wherein the sterile, aqueous pharmaceutical composition is free of any type of enzymatic, chemical or biochemical molecule capable of breakdown of the peptide at its termini that is sequential degradation of the peptide at a terminal end thereof in the absence of the C-terminus amidation and the N-terminus acetylation.
10. The method of claim 9 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.001% to 1% (w/w).
11. The method of claim 9 , wherein the pharmaceutically acceptable aqueous carrier comprises a buffer.
12. The method of claim 9 , wherein the sterile, aqueous, topical pharmaceutical composition further comprises a tonicity agent.
13. The method of claim 9 , wherein the sterile, aqueous, topical pharmaceutical composition further comprises a viscosity building agent.
14. The method of claim 9 , wherein the ocular surface is the ocular surface of a subject that has Sjogren's Syndrome.
15. The method of claim 9 , wherein the ocular surface is the ocular surface of a subject that is recovering from photorefractive keratectomy or laser-assisted in situ keratomileusis.
16. The method of claim 9 , wherein the ocular surface is the ocular surface of a subject that has Sjogren's Syndrome,
wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.001% to 1% (w/w),
wherein the pharmaceutically acceptable aqueous carrier comprises a buffer, and
wherein the sterile, aqueous, topical pharmaceutical composition further comprises,
a tonicity agent, and
a surfactant.
17. The method of claim 10 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.005% (w/w).
18. The method of claim 16 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.005% (w/w).
19. The sterile, aqueous pharmaceutical composition of claim 2 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.005% (w/w).
20. The sterile, aqueous pharmaceutical composition of claim 8 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.005% (w/w).
21. A method of treating dry eye, the method comprising:
topically administering a therapeutically effective amount of the pharmaceutical composition of claim 1 to an ocular surface of a subject suffering from dry eye.
22. The method of claim 21 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.001% to 1% (w/w).
23. The method of claim 21 , wherein the pharmaceutically acceptable aqueous carrier comprises a buffer.
24. The method of claim 21 , wherein the sterile, aqueous, topical pharmaceutical composition further comprises a tonicity agent.
25. The method of claim 21 , wherein the sterile, aqueous, topical pharmaceutical composition further comprises a viscosity building agent.
26. The method of claim 21 , wherein the subject has Sjogren's Syndrome.
27. The method of claim 21 , wherein the subject is recovering from photorefractive keratectomy or laser-assisted in situ keratomileusis.
28. The method of claim 21 , wherein the subject has Sjogren's Syndrome,
wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.001% to 1% (w/w),
wherein the pharmaceutically acceptable aqueous carrier comprises a buffer, and
wherein the sterile, aqueous, topical pharmaceutical composition further comprises,
a tonicity agent, and
a surfactant.
29. The method of claim 22 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.005% (w/w).
30. The method of claim 28 , wherein the peptide, or pharmaceutically acceptable salt thereof, is at a concentration of 0.005% (w/w).