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 liquid oral pharmaceutical formulation suitable for treating a human subject with an endogenous 11-cis-retinal deficiency consisting essentially of 9-cis-retinyl acetate in soybean oil and an anti-oxidant, wherein the soybean oil is U.S.P. grade soybean oil.
2. The formulation of claim 1 , wherein said formulation is not in the form of a capsule.
3. The formulation of claim 1 , wherein the 9-cis-retinyl acetate is present up to 30% by weight of the formulation.
4. The formulation of claim 1 , wherein the 9-cis-retinyl acetate is present up to 25% by weight of the formulation.
5. The formulation of claim 1 , wherein the 9-cis-retinyl acetate is present up to 10% by weight of the formulation.
6. The formulation of claim 1 , wherein the 9-cis-retinyl acetate is present up to 5% by weight of the formulation.
7. The formulation of claim 1 , wherein the 9-cis-retinyl acetate is present from about 1.25 to 20 mg/mL in the formulation.
8. The formulation of claim 1 , wherein the 9-cis-retinyl acetate is present at about 20 mg/mL in the formulation.
9. The formulation of claim 1 , wherein the anti-oxidant comprises a-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbyl palmitate, propyl gallate, tert-butyl hydroquinone (TBHQ), or a chelating agent, or a combination thereof.
10. The formulation of claim 1 , wherein the anti-oxidant comprises butylated hydroxyanisole (BHA).
11. The formulation of claim 1 , wherein the formulation comprises about 0.1% by weight to volume of the anti-oxidant.
12. The formulation of claim 1 , wherein the 11-cis-retinal deficiency is due to an RPE65 mutation.
13. The formulation of claim 1 , wherein the 11-cis-retinal deficiency is due to an LRAT mutation.
14. The formulation of claim 1 , wherein the human subject has Leber congenital amaurosis (LCA).
15. The formulation of claim 1 , wherein the human subject has Retinitis Pigmentosa (RP).
16. The formulation of claim 1 , wherein the formulation is configured to provide a dosage of about 1.25-40 mg/m 2 of the 9-cis-retinyl acetate by body surface area to the subject.
17. The formulation of claim 1 , wherein the formulation is configured to provide a dosage of about 40 mg/m 2 of the 9-cis-retinyl acetate by body surface area to the subject.
18. The formulation of claim 1 , wherein the formulation is in the form of an oil-in-water emulsion.
19. The formulation of claim 1 , wherein the formulation is configured for single dosing, intermittent dosing or daily dosing.
20. The formulation of claim 1 , wherein the formulation is packaged in an amber container.