Pharmaceutical formulations comprising 9-cis-retinyl esters in a lipid vehicle
Pharmaceutical formulations comprising 9-cis-retinyl esters in a lipid vehicle are described as retinoid replacement therapies for treating retinal degenerations in humans.
1. A method of treating a human subject with an endogenous 11-cis-retinal deficiency, comprising administering a liquid oral pharmaceutical formulation suitable for ophthalmologic use consisting essentially of: 9-cis-retinyl acetate in soybean oil and an anti-oxidant, wherein said formulation is not in the form of a capsule.
2. The method of claim 1 , wherein said soybean oil is highly refined soybean oil.
3. The method of claim 1 , wherein said soybean oil is U.S.P. grade soybean oil.
4. The method of claim 1 , wherein said formulation comprises up to 30% by weight of the 9-cis-retinyl acetate.
5. The method of claim 1 , wherein said formulation comprises up to 25% by weight of the 9-cis-retinyl acetate.
6. The method of claim 1 , wherein said formulation comprises up to 10% by weight of the 9-cis-retinyl acetate.
7. The method of claim 1 , wherein said formulation comprises up to 5% by weight of the 9-cis-retinyl acetate.
8. The method of claim 1 , wherein said formulation comprises about 1.25-20 mg/mL of the 9-cis-retinyl acetate.
9. The method of claim 1 , wherein said formulation comprises about 20 mg/mL of the 9-cis-retinyl acetate.
10. The method of claim 1 , wherein said anti-oxidant comprises α-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbyl palmitate, propyl gallate, tert-butyl hydroquinone (TBHQ), or a chelating agent, or a combination thereof.
11. The method of claim 10 , wherein said anti-oxidant comprises butylated hydroxyanisole (BHA).
12. The method of claim 1 , wherein said formulation comprises about 0.1% by weight to volume of the anti-oxidant.
13. The method of claim 1 , wherein said formulation provides a peak plasma concentration of active metabolites of said 9-cis-retinyl acetate at about 3-6 hours after administration.
14. The method of claim 13 , wherein said active metabolites comprise 9-cis-retinol and 9-cis-retinyl esters.
15. The method of claim 1 , wherein said 11-cis-retinal deficiency is due to an RPE65 mutation.
16. The method of claim 1 , wherein said 11-cis-retinal deficiency is due to an LRAT mutation.
17. The method of claim 1 , wherein said subject has Leber congenital amaurosis (LCA).
18. The method of claim 1 , wherein said subject has Retinitis Pigmentosa (RP).
19. The method of claim 1 , wherein said administration of said formulation provides a dosage of about 1.25-40 mg/m 2 of said 9-cis-retinyl acetate by body surface area to said subject.
20. The method of claim 19 , wherein said administration of said formulation provides a dosage of about 40 mg/m 2 of said 9-cis-retinyl acetate by body surface area to said subject.
21. The method of claim 1 , wherein said formulation is in the form of an oil-in-water emulsion.
22. The method of claim 1 , wherein said formulation is suitable for single dosing, intermittent dosing or daily dosing.
23. The method of claim 1 , wherein said formulation is packaged in an amber container.