Enterically coated cysteamine, cystamine and derivatives thereof
The disclosure provides oral cysteamine and cystamine formulations useful for treating cystinosis and neurodegenerative diseases and disorders. The formulations provide controlled release compositions that improve quality of life and reduced side-effects.
1. A composition comprising:
delayed and extended release enterically coated cysteamine bitartrate granules, each of the cysteamine bitartrate granules comprising:
a core granule comprising cysteamine bitartrate and a binder; and
an enteric coating surrounding the core granule,
wherein the enteric coating releases the cysteamine bitartrate at a pH of 4.5 or greater and provides a time to C max of between 2-4 hours after administration.
2. The composition of claim 1 , wherein the enteric coating is selected from the group consisting of polymerized gelatin, shellac, methacrylic acid copolymer type C NF, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose proprionate phthalate, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose (CMEC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and acrylic acid polymers and copolymers, typically formed from methyl acrylate, ethyl acrylate, methyl methacrylate and/or ethyl methacrylate with copolymers of acrylic and methacrylic acid esters.
3. The composition of claim 1 , wherein the delayed and extended release enterically coated cysteamine bitartrate granules are loaded in a capsule.
4. The composition of claim 1 , wherein the composition is formulated for oral administration.
5. The composition of claim 1 , wherein the composition comprises a dose of cysteamine bitartrate of about 0.5-1.0 g/m 2 body surface area.
6. The composition of claim 1 , wherein the composition comprises a dose of cysteamine bitartrate of about 0.7-0.8 g/m 2 body surface area.
7. The composition of claim 1 , wherein the enteric coating begins dissolution in the small intestine.
8. The composition of claim 1 , wherein the cysteamine bitartrate is released during transit in the small intestine.
9. The composition of claim 1 , wherein the composition further comprises a stabilizer.
10. A method of treating a subject with cystinosis comprising administering a composition of claim 1 less than 4 times per day, wherein the total daily dose of cysteamine bitartrate is about 1.35 g/m 2 body surface area or less.
11. A method of treating a subject with cystinosis comprising administering a composition of claim 1 at a dose of cysteamine bitartrate of about 0.5-1.0 g/m 2 body surface area.
12. A method of treating a subject with cystinosis comprising administering a composition of claim 1 less than 4 times per day in an amount to provide white blood cell cystine suppression with a 12 hour level below 1 nm/½ cystine/mg protein.
13. A method of treating a subject with cystinosis comprising administering a composition of claim 1 twice per day in an amount to provide white blood cell cystine suppression with a 12 hour level below 1 nm/½ cystine/mg protein.
14. A method of treating a subject with Huntington's Disease comprising administering the composition of claim 1 comprising a dose of about 100 mg to 1000 mg of cysteamine bitartrate.