Unit dosage forms for treatment of vasoconstriction and related conditions

• US 5,849,338 A
• Filed: 08/26/1997
• Issued: 12/15/1998
• Est. Priority Date: 04/10/1996
• Status: Expired due to Fees

• Current Assignee: ChronoRX, LLC
• Original Assignee: ChronoRX, LLC
• Inventors: Richardson, Kenneth T., Pearson, Don C.
• Primary Examiner(s): JORDAN, KIMBERLY R
• Application Number:
  US08/849,068
• Time in Patent Office: 476 Days
• Field of Search: 424/682, 424/702, 514/249, 514/419, 514/458, 514/474, 514/929
• US Class Current: 424/682
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 33/04 Sulfur, selenium or tellurium; Compounds thereof
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof

Abstract

Magnesium is formulated in combination with vitamin E, vitamin C, folate, selenium, and optionally melatonin in a unit dosage form for oral administration, for the treatment of vasoconstriction and the physiological and pathological conditions giving rise to vasoconstriction. These active agents complement each other in suppressing these conditions, using a variety of mechanisms operating in conjunction with one another. The inclusion of magnesium in a plurality of forms provides additional advantages in terms of controlling and sustaining the release of magnesium in locations along the digestive tract where the magnesium will have its greatest effectiveness as a therapeutic agent, thus improving control over thge clinical bioavailability of magnesium and in improving the selection of appropriate therapeutic ranges.

Claims

1. A unit dosage form for treatment of vasoconstriction and physiological conditions giving rise thereto, said dosage form comprising a combination of the following components in therapeutically effective amounts:

(i) magnesium;

(ii) a member selected from the group consisting of α

-tocopherol, β

-tocopherol, and esters thereof;

(iii) a member selected from the group consisting of ascorbic acid and ascorbate ion;

(iv) a member selected from the group consisting of folic acid and folate ion;

(v) selenium; and

(vi) melatonin.

2. A unit dosage form in accordance with claim 1 in which said components are included in the following ranges of amounts:

(i) about 20 mg to about 700 mg;

(ii) about 15 IU to about 1,000 IU;

(iii) about 30 mg to about 1,000 mg;

(iv) about 0.05 mg to about 0.225 mg;

(v) about 0.005 mg to about 0.15 mg; and

(vi) about 0.10 mg to about 40 mg.

3. A unit dosage form in accordance with claim 1 in which said components are included in the following ranges of amounts:

(i) about 40 mg to about 180 mg;

(ii) about 20 IU to about 400 IU;

(iii) about 40 mg to about 500 mg;

(iv) about 0.10 mg to about 0.20 mg;

(v) about 0.005 to about 0.035 mg; and

(vi) about 0.5 mg to about 30 mg.

4. A unit dosage form in accordance with claim 1 in which the weight ratios of components (ii), (iii), and (iv) relative to component (i) are in the following ranges:

(ii) about 0.2;

1 to about 2;

1;

(iii) about 0.2;

1 to about 2;

1; and

(iv) about 0.0003;

1 to about 0.0030;

1.

5. A unit dosage form in accordance with claim 1 in which the weight ratios of components (ii), (iii), and (iv) relative to component (i) are in the following ranges:

(ii) about 0.5;

1 to about 1;

1;

(iii) about 0.5;

1 to about 1;

1; and

(iv) about 0.00075;

1 to about 0.0020;

1.

6. A unit dosage form in accordance with claim 1 in which said magnesium is supplied in the form of a member selected from the group consisting of magnesium lactate, magnesium citrate, magnesium stearate, magnesium acetate, magnesium ascorbate, magnesium malate, magnesium orotate, magnesium diglycinate, and magnesium oxide.

7. A unit dosage form in accordance with claim 1 in which said magnesium is supplied as a combination of magnesium compounds comprising magnesium citrate and magnesium ascorbate.

8. A unit dosage form in accordance with claim 1 in which said magnesium is supplied as a combination of magnesium compounds comprising magnesium acetate, magnesium citrate, and magnesium oxide.

9. A unit dosage form in accordance with claim 1 in which said magnesium is supplied as a combination of magnesium compounds comprising magnesium lactate, magnesium acetate, magnesium citrate, magnesium ascorbate, and magnesium oxide.

10. A unit dosage form in accordance with claim 1 in which component (ii) is a member selected from the group consisting of a-tocopherol, a-tocopherol acid succinate, and α

-tocopherol acetate.

11. A unit dosage form in accordance with claim 1 in which said components are formulated as a member selected from the group consisting of a tablet, a gelatin capsule, a solution, a suspension, and a powder.

12. A unit dosage form in accordance with claim 1 in which said components are formulated as a substantially homogeneous tablet that releases all of said components into the stomach upon ingestion for contact with gastric fluid.

13. A unit dosage form in accordance with claim 12 in which said components comprise:

(a) magnesium oxide,

(b) magnesium acetate,

(c) magnesium ascorbate,

(d) α

-tocopherol succinate,

(e) folic acids

(f) selenium, and

(g) melatonin.

14. A unit dosage form in accordance with claim 13 in which said components further comprise magnesium citrate.

15. A unit dosage form in accordance with claim 13 in which components (a) through (g) are present in the following ranges of amounts:

(a) about 50 mg to about 100 mg,

(b) about 40 mg to about 100 mg,

(c) about 150 mg to about 250 mg,

(d) about 50 IU to about 100 IU,

(e) about 0.03 mg to about 0.3 mg,

(f) about 0.007 mg to about 0.02 mg, and

(g) about 0.5 to about 30 mg.

16. A unit dosage form in accordance with claim 13 in which said components further comprise:

magnesium citrate.

17. A unit dosage form in accordance with claim 16 in which component (h) is present in the amount of about 50 mg to about 100 mg.

18. A unit dosage form in accordance with claim 1 in which said components are formulated as a combination tablet in which said components are present as first and second portions separately formulated such that said first portion is released into the stomach upon ingestion for contact with gastric fluid, and said second portion is protected from release until reaching the intestine.

19. A unit dosage form in accordance with claim 18 in which the components of said second portion are coated with an acid-resistant protective coating that substantially prevents penetration thereof by gastric fluid but is penetrable by intestinal fluid.

20. A unit dosage form in accordance with claim 18 in which said components of said first portion comprise:

(a) a member selected from the group consisting of α

-tocopherol, β

-tocopherol, and esters thereof,

(b) a member selected from the group consisting of folic acid and folate ion,

(c) selenium, and

(d) magnesium compounds;

and said components of said second portion comprise further magnesium compounds.

21. A unit dosage form in accordance with claim 18 in which said components of said first portion comprise:

(a) α

-tocopherol succinate,

(b) folic acid,

(c) selenium,

(d) magnesium oxide,

(e) magnesium diglycinate, and

(f) magnesium ascorbate,

and said components of said second portion comprise;

(g) magnesium citrate,

(h) magnesium acetate, and

(i) melatonin.

22. A unit dosage form in accordance with claim 21 in which components (a) through (i) are present in the following ranges of amounts:

(a) about 50 IU to about 100 IU,

(b) about 0.03 mg to about 0.3 mg,

(c) about 0.007 mg to about 0.20 mg,

(d) about 50 mg to about 100 mg,

(e) about 50 mg to about 200 mg,

(f) about 150 mg to about 250 mg,

(g) about 50 mg to about 100 mg,

(h) about 40 mg to about 100 mg,

(i) about 0.5 mg to about 30 mg.