Enterically coated cysteamine, cystamine and derivatives thereof

• US 9,925,158 B2
• Filed: 07/21/2017
• Issued: 03/27/2018
• 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
• Primary Examiner(s): AHMED, HASAN SYED
• Application Number:
  US15/656,903
• Publication Number:
  US 20170319524A1
• Time in Patent Office: 249 Days
• Field of Search: None
• 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. A dosage form comprising enterically-coated granules having a core comprising cysteamine bitartrate and cystamine or a pharmaceutically-acceptable salt thereof;

at least one pharmaceutically acceptable binder; and

an enteric coating surrounding the core, wherein the enterically-coated granules release cysteamine and cystamine or a pharmaceutically-acceptable salt thereof at a pH of 4.5-6.5.

2. 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 cystamine is about 1.35 g/m² body surface area or less.

3. A method of treating a subject with cystinosis comprising administering a composition of claim 1, wherein each administration comprises an amount of cysteamine bitartrate that would yield a dose of 100 to 1000 mg cysteamine free base.

4. 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 nmol/½

cystine/mg protein.

5. 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 nmol/½

cystine/mg protein.

6. A method of treating a subject with Huntington'"'"'s Disease comprising administering the composition of claim 1, wherein each administration comprises an amount of cysteamine bitartrate that would yield a dose of 100 to 1000 mg cysteamine free base.