SLOW RELEASE MAGNESIUM COMPOSITION AND USES THEREOF

• US 20110020443A1
• Filed: 07/01/2010
• Published: 01/27/2011
• Est. Priority Date: 07/01/2009
• Status: Active Grant

• Current Assignee: Neurocentria, Inc.
• Original Assignee: Magceutics, Inc.
• Inventors: Liu, Guosong, Mao, Fei
• Granted Patent: US 8,377,473 B2
• Time in Patent Office: Days
• US Class Current: 424/464
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/191 having two or more hydroxy groups, e.g. gluconic acid
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/28 Compounds containing heavy metals
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/14 Alkali metal chlorides; Alkaline earth metal chlorides
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2027 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: 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 3/02 Nutrients, e.g. vitamins, minerals

Abstract

The present invention provides compositions that contain magnesium and threonate, or a threonate precursor molecule, formulated for extended or modified release to provide physiological concentrations over a desired time period. The extended release or modified release form is particularly useful in providing Mg to a subject while avoiding adverse side effects such as diarrhea.

Claims

1. An oral dosage form comprising magnesium (Mg) and threonate (T), wherein said threonate comprises one or more of a threonate salt or a threonate precursor, wherein said oral dosage form has an in vitro dissolution profile in a dissolution medium, and wherein said dissolution profile ranges between less than or equal to 5% in about 2 hours, less than 10% in about 4 hours, less than 40% in about 6 hours, greater than or equal to 60% in about 10 hours, and greater than or equal to 80% in about 12 hours as measured using a USP type II (paddle) dissolution system at 75 rpm, at a temperature of 37°

C.

2. The oral dosage form of claim 1, wherein said magnesium and threonate in said oral dose form are encapsulated in a tablet.

3. The oral dosage form of claim 1, wherein at least a portion of said magnesium (Mg) and threonate (T) are complexed in a salt form of MgT₂.

4. The oral dosage form of claim 1, wherein at least a portion of said magnesium (Mg) and threonate (T) are complexed in a salt form of MgT₂ present in an amount equal to at least about 20 mg of Mg by weight.

6. The oral dosage form of claim 1, wherein said threonate precursor comprises a threonic acid, a threonate ester, or a threonate lactone.

7. The oral dosage form of claim 1, wherein said magnesium (Mg) is present in an amount greater than about 1% by weight.

10. The oral dosage form of claim 1, wherein said magnesium (Mg) is complexed with an anion selected from the group consisting of chloride, taurinate, lactate, gluconate, citrate, malate, succinate, sulfate, propionate, hydroxide, oxide, orotate, phosphate, borate, salicylate, carbonate, bromide, stearate, an amino acid, butyrate, aspartate, ascorbate, picolinate, pantothenate, nicotinate, benzoate, phytate, caseinate, palmitate, pyruvate, and threonate.

11. The oral dosage form of claim 1, further comprising a metal ion selected from the group consisting of calcium, potassium, sodium, chromium, iron, selenium, zinc, manganese, molybdenum, vanadium, and lithium.

12. The oral dosage form of claim 1, further comprising one or more antioxidants selected from the group consisting of resveratrol, ellagic acid, quecertin, lipoic acid and vitamin C.

13. The oral dosage form of claim 1, wherein said dissolution profile ranges between less than 5% in about 2 hours, less than 10% in about 4 hours, less than 40% in about 6 hours, greater than or equal to 60% in about 10 hours, and greater than or equal to 80% in about 12 hours as measured using a USP type II (paddle) dissolution system at 75 rpm, at a temperature of 37°

C.

14. The oral dosage form of claim 1, wherein 75% to 100% of said magnesium (Mg) and threonate (T) in said oral dose form are provided in a controlled release dosage form.

27. The oral dosage form of claim 1 or 23, wherein said oral dosage form is effective in increasing the life span of a subject on a high calorie diet.

31. The oral dosage form of claim 27, wherein said oral dosage form is administered to a human subject at a dose between about 1 mg elemental magnesium/kg/day to about 16 mg elemental magnesium/kg/day.

32. The oral dosage form of claim 27, wherein the oral dosage form increases survival rate by at least about 40% in subjects who are on a high calorie diet for at least about 60 weeks.

39. A method of treating a condition related to magnesium deficiency comprising administering to a subject in need thereof an oral dosage form of any of claims 1, 23, and 33.

5. (canceled)

8. (canceled)

9. (canceled)

15-22. -22. (canceled)

23. An oral dosage form comprising between about 10 mg to 500 mg elemental magnesium (Mg), wherein said oral dosage form is a controlled release formulation, and wherein upon administering said oral dosage form to a Sprague-Dawley rat at a dosage of equal to or less than 75 mg/kg/day yields an incidence of diarrhea of less than 20%.

24. The oral dosage form of claim 23, wherein the incidence of diarrhea is less than 20% when administered at a dosage of equal to or less than 75 mg/kg/day for at least about 3 days.

26. The oral dosage form of claim 23, wherein said oral dosage form provides for an incidence of diarrhea of less than 50% when administered at a dosage of equal to or less than about 130 mg/kg/day.

25. (canceled)

28-30. -30. (canceled)

33. An oral dosage form comprising magnesium (Mg) and threonate (T), wherein said threonate comprises one or more of a threonate salt or a threonate precursor, wherein said oral dosage form is readily absorbed or retained upon administering said oral dosage form to a subject at least about 50% of said administered magnesium is absorbed in said subject, or that at least 30% of the magnesium administered to the subject is retained over a period of at least two days when said oral dosage form is administered at a dose of 20 mg/kg/day or higher.

34-38. -38. (canceled)

40-46. -46. (canceled)