CYCLOSPORIN COMPOSITIONS
Disclosed herein are therapeutic methods, compositions, and medicaments related to cyclosporine.
1 . A composition comprising cyclosporin A at a concentration of from about 0.0001% (w/v) to less than about 0.05% (w/v).
2 . The composition of claim 1 which is an aqueous solution.
3 . The concentration of claim 1 wherein the concentration of cyclosporin A is from about 0.02% (w/v) to about 0.04% (w/v).
4 . The composition of claim 2 wherein the concentration of cyclosporin A is from about 0.02% (w/v) to about 0.04% (w/v).
5 . The composition of claim 2 containing no ethanol.
6 . The composition of claim 2 containing no hyaluronic acid.
7 . The composition of claim 2 containing no cyclodextrin A.
8 . The composition of claim 6 containing no cyclodextrin.
9 . The composition of claim 8 containing no ethanol.
10 . The composition of claim 9 containing no vitamin E TPGS.
11 . The composition of claim 9 containing no hyaluronic acid.
12 . The composition claim 1 wherein topical administration of one 35 μL drop of said composition to each eye of a female New Zealand white rabbit provides to the corneas of said rabbit at least about 500 ng of cyclosporin A per gram of cornea of said rabbit at 30 minutes after said topical administration.
13 . The composition of claim 1 wherein topical administration of one 35 μL drop of said composition to each eye of a female New Zealand white rabbit provides to the corneas of said rabbit at least about 1000 ng of cyclosporin A per gram of cornea of said rabbit at 30 minutes after said topical administration.
14 . The composition of claim 1 wherein topical administration of one 35 μL drop of said composition to each eye of a female New Zealand white rabbit provides to the corneas of said rabbit at least about 1400 ng of cyclosporin A per gram of cornea of said rabbit at 30 minutes after said topical administration.
15 . The composition of claim 1 wherein topical administration of one 35 μL drop of said composition to each eye of a female New Zealand white rabbit provides to the corneas of said rabbit at least about 17000 ng·hr of cyclosporin A per gram of cornea of said rabbit over a period of 24 hours after said topical administration.
16 . The composition of claim 2 wherein topical administration of one 35 μL drop of said composition to each eye of a female New Zealand white rabbit provides to the conjunctivas of said rabbit at least about 3300 ng·hr of cyclosporin A per gram of conjunctiva of said rabbit over a period of 24 hours after said topical administration.
17 . The composition of claim 2 wherein said composition is an aqueous solution containing from 0.005% (w/v) to about 0.04% (w/v) cyclosporin A, wherein topical administration of one 35 μL drop of said composition to each eye of a New Zealand rabbit provides at least about 17000 ng·hr of cyclosporin A per gram of cornea to the corneas of said rabbit as determined by:
topically administering said composition to each eye of each of 15 female New Zealand white rabbit test subjects; and
determining the amount of cyclosporin A in the corneas of three subjects at times of about 0.5 hours, about 2 hours, about 6 hours, about 12 hours, and about 24 after administration to said subject;
wherein the amount of cyclosporin A in the cornea is determined only once for each subject.
18 . The composition of claim 2 wherein said composition is an aqueous solution containing from 0.005% (w/v) to about 0.04% (w/v) cyclosporin A, wherein topical administration of one 35 μL drop of said composition to each eye of a New Zealand rabbit provides at least about 6000 ng of cyclosporin A per gram of conjunctiva to the conjunctivas of said rabbit as determined by:
topically administering said composition to each eye of each of 15 female New Zealand white rabbit test subjects; and
determining the amount of cyclosporin A in the conjunctivas of three subjects at times of about 0.5 hours, about 2 hours, about 6 hours, about 12 hours, and about 24 after administration to said subject;
wherein the amount of cyclosporin A in the conjunctiva is determined only a single time for each subject.
19 . The composition of claim 1 further comprising a surfactant.
20 . The composition of claim 1 further comprising a preservative.
21 . A method comprising topically administering a composition according to claim 1 to an eye of a mammal in need thereof to enhance or restore lacrimal gland tearing.
22 . The method of claim 21 , wherein said method increases tear production in a tear-deficient eye.
23 . The method of claim 21 , wherein said method is effective in treating keratoconjunctivitis sicca.
24 . The method of claim 21 , wherein said method is effective in treating dry eye disease.
25 . The method of claim 21 wherein the mammal is a human patient, and wherein less than 10% of human patients suffer burning or stinging when said composition is administered only once a day for a period of three months.
26 . The method of claim 21 wherein the mammal is a human patient, and wherein less than 10% of human patients suffer ocular burning when said composition is administered only once a day for a period of three months.
27 . The method of claim 21 wherein the composition is administered only once a day.
28 . An aqueous solution comprising cyclosporin A at a concentration of from 0.01% (w/v) to 0.019% (w/v).
29 . The composition of claim 28 wherein the concentration of cyclosporin A is about 0.015% (w/v).
30 . An aqueous solution comprising cyclosporin A at a concentration of from 0.01% (w/v) to 0.02% (w/v) and more than 95% (w/w) water.
31 . An aqueous solution comprising cyclosporin A at a concentration of from 0.01% (w/v) to 0.02% (w/v) and does not contain sodium hyaluronate at a concentration of 0.05% (w/v).
32 . The aqueous solution of claim 31 which contains no sodium hyaluronate.
33 . An aqueous solution comprising cyclosporin A at a concentration of from 0.01% (w/v) to 0.02% (w/v) and does not contain polysorbate 80 at a concentration of 0.05% (w/v).
34 . The aqueous solution of claim 31 which contains from 0.1% to 1% polysorbate 80.
35 . An kit comprising a container comprising an aqueous solution comprising cyclosporin A at a concentration of from 0.005% (w/v) to 0.03% (w/v), wherein said container is capable of dispensing eye drops, and wherein said composition has been stored in said container for at least two months.
36 . A composition comprising cyclosporin A at a concentration of from 0.01% (w/v) to 0.02% (w/v) and a preservative.
37 . The composition of claim 36 wherein the concentration of cyclosporin A is about 0.015% (w/v).
38 . The composition of claim 2 wherein the cyclosporin A concentration is about 0.04% (w/v).
39 . The composition of claim 2 wherein the cyclosporin A concentration is about 0.005% (w/v).