Methods of treating chronic dry eye disease using C16:1n7-palmitoleate and derivatives thereof
The present technology provides methods for preventing or treating dry eyes in a subject in need thereof. The methods include administering to the subject an effective amount of a composition comprising C16:1n7-palmitoleate, its derivatives, pharmaceutically acceptable salts thereof, or a combination thereof.
1. A method for treating dry eyes in a subject in need thereof comprising administering to the subject an effective amount of a composition comprising a C16:1n7-palmitoleate derivative and a palmitate derivative, wherein the composition has a ratio of the C16:1n7-palmitoleate derivative to the palmitate derivative of 1.5:1 to 100:1;
(a) wherein the C16:1n7-palmitoleate derivative is palmitoleic acid, a pharmaceutically acceptable salt of palmitoleate, a (C 1 -C 4 )alkyl ester of palmitoleate, a monoglyceride of palmitoleic acid, a diglyceride of palmitoleic acid, or a triglyceride of palmitoleic acid;
(b) wherein the palmitate derivative is palmitic acid, a pharmaceutically acceptable salt of palmitate, a (C 1 -C 4 )alkyl ester of palmitate, a monoglyceride of palmitic acid, a diglyceride of palmitic acid, or a triglyceride of palmitic acid; and
(c) wherein administration of the composition results in an increase in meibomian gland secretion in the subject relative to that observed prior to administration, thereby treating dry eyes in the subject.
2. The method of claim 1 , wherein the composition further comprises at least 20wt % of the C16:1n7-palmitoleate derivative.
3. The method of claim 1 , wherein the composition further comprises a C18:1n9-oleate derivative, wherein the C18:1n9-oleate derivative is oleic acid, a pharmaceutically acceptable salt of oleate, a (C 1 -C 4 )alkyl ester of oleate, a monoglyceride of oleic acid, a diglyceride of oleic acid, or a triglyceride of oleic acid.
4. The method of claim 1 , wherein the subject has been diagnosed with dry eyes or dry eye syndrome.
5. The method of claim 1 , wherein the subject is human.
6. The method of claim 1 , further comprising simultaneously, sequentially, or separately administrating at least one additional therapeutic agent, wherein the at least one additional therapeutic agent, is selected from the group consisting of cyclosporine ophthalmic emulsion, antibiotics, and hydroxypropyl cellulose insert.
7. The method of claim 1 , wherein administration of the composition treats, or ameliorates one or more signs and/or symptoms of dry eyes.
8. The method of claim 7 , wherein the signs and/or symptoms are selected from the group consisting of stinging, burning, or scratchy sensation in the eyes, stringy mucus in or around the eyes, increased eye irritation from smoke or wind, eye fatigue, sensitivity to light, eye redness, sensation of foreign object in eyes, difficulty wearing contact lenses, periods of excessive tearing, swollen eyes, eye discomfort, eye pain, and blurred vision.
9. The method of claim 1 , wherein the subject displays tear osmolarity less than 308mOsms/L after administration of the composition.
10. The method of claim 1 , wherein the composition is administered daily for 4weeks or more.
11. The method of claim 1 , wherein administration of the composition results in at least a 5% reduction in tear osmolarity values in the subject relative to that observed prior to administration.
12. A method for increasing meibomian gland secretion in a subject in need thereof comprising administering to the subject an effective amount of a composition comprising a C16:1n7-palmitoleate derivative and a palmitate derivative, wherein the ratio of the C16:1n7-palmitoleate derivative to the palmitate derivative is 1.5:1to 100:1;
wherein the C16:1n7-palmitoleate derivative is palmitoleic acid, a pharmaceutically acceptable salt of palmitoleate, a (C 1 -C 4 )alkyl ester of palmitoleate, a monoglyceride of palmitoleic acid, a diglyceride of palmitoleic acid, or a triglyceride of palmitoleic acid; and
wherein the palmitate derivative is palmitic acid, a pharmaceutically acceptable salt of palmitate, a (C 1 -C 4 )alkyl ester of palmitate, a monoglyceride of palmitic acid, a diglyceride of palmitic acid, or a triglyceride of palmitic acid.
13. The method of claim 12 , wherein the subject has been diagnosed with dry eyes or dry eye syndrome.
14. The method of claim 1 , wherein the composition is administered orally, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.
15. The method of claim 1 , wherein the composition has a ratio of the C16:1n7-palmitoleate derivative to the palmitate derivative of 1.8:1to 100:1.
16. The method of claim 12 , wherein the ratio of the C16:1n7-palmitoleate derivative to the palmitate derivative is 1.8:1to 100:1.