ENTERICALLY COATED CYSTEAMINE, CYSTAMINE AND DERIVATIVES THEREOF

• US 20170319522A1
• Filed: 07/21/2017
• Published: 11/09/2017
• Est. Priority Date: 01/27/2006
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Dohil, Ranjan, Schneider, Jerry
• Granted Patent: US 9,925,156 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/1605 Excipients; Inactive ingredients
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2873 Proteins, e.g. gelatin
• CPC Class Codes: A61K 9/288 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/282
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5005 Wall or coating material
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5057 Gelatin
• CPC Class Codes: A61K 9/5063 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/5015
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

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.

Claims

1. An enterically-coated composition comprising a core of cysteamine bitartrate and cystamine or a pharmaceutically-acceptable salt thereof mixed with one or more pharmaceutically-acceptable binders, wherein the enteric coating begins to dissolve in an aqueous solution at a pH between about 4.5 to about 5.5.

2. The composition of claim 1, wherein the composition is in the form of a tablet or granules.

3. The composition of claim 2, wherein the granules are loaded into a capsule.

4. The composition of claim 1, wherein the enteric coating comprises a compound selected from the group consisting of polymerized gelatin, shellac, methacrylic acid copolymer type CNF, 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 formed from methyl acrylate, ethyl acrylate, methyl methacrylate and/or ethyl methacrylate with copolymers of acrylic and methacrylic acid esters.

5. The composition of claim 4, wherein the enteric coating comprises a methacrylic acid ester.

6. The composition of claim 1, wherein the composition is formulated for oral administration.

7. A method of treating a subject with nephropathic cystinosis comprising administering a composition of claim 1 twice per day.

8. The method of claim 7, wherein each administration comprises an amount of cysteamine bitartrate that would yield a dose of 100 to 1000 mg cysteamine free base.

9. The method of claim 7, wherein administration maintains white blood-cell cysteine concentration at less than 1 nmol ½

cystine/mg protein.

10. The method of claim 8, wherein the total daily dose of cysteamine free base is about 1.35 g/m² body surface area.

11. A method of lowering the cystine content of cells in patients having nephropathic cystinosis comprising administering a composition of claim 1.

12. The method of claim 11, wherein each administration comprises an amount of cysteamine bitartrate that would yield a dose of 100 to 1000 mg cysteamine free base.

13. The method of claim 11, wherein administration maintains white blood-cell cysteine concentration at less than 1 nmol ½

cystine/mg protein.

14. The method of claim 12, wherein the total daily dose of cysteamine free base is about 1.35 g/m² body surface area.