Formulations Including Monovalent Alginate to Enhance Effectiveness of Administered Digestive Enzymes

• US 20080145355A1
• Filed: 12/14/2007
• Published: 06/19/2008
• Est. Priority Date: 12/14/2006
• Status: Active Grant

• Current Assignee: Master Supplements, Inc.
• Original Assignee: Master Supplements, Inc.
• Inventors: Porubcan, Randolph S.
• Granted Patent: US 9,011,843 B2
• Time in Patent Office: Days
• US Class Current: 424/94.21
• 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 31/733 Fructosans, e.g. inulin
• CPC Class Codes: A61K 31/734 Alginic acid
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 38/48 acting on peptide bonds (3.4)
• CPC Class Codes: A61K 38/4873 Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system

Abstract

Disclosed are alginate formulations that help protect digestive enzymes in the formulations from denaturation during passage through the acidic stomach environment, and from other sources, following ingestion. The formulation changes consistency to permit release of the enzymes in the less-acidic gut. They contain monovalent alginate salts (sodium, potassium and ammonium alginate) but are designed to not include significant quantities of compounds which would generate divalent ions and thereby convert the monovalent alginate to a divalent alginate when exposed to aqueous solution. A buffering agent that does not react with the digestive enzymes or the monovalent alginate, and which does not generate divalent ions on exposure to aqueous solution, can be included. A chelating agent which binds divalent ions may be administered with the formulation. Additionally, the formulation may be admixed with inert excipients suitable for oral delivery. It is preferable that the ingredients are dried before formulation.

Claims

1. A formulation for administration to aid in digestion, comprising:

a capsule containing digestive enzymes, a monovalent alginate, and wherein the formulation does not include quantities of compounds which would generate significant divalent ions and thereby convert significant quantities of the monovalent alginate to an insoluble divalent alginate, when exposed to aqueous solution.

2. The formulation of claim 1 wherein the monovalent alginate is sodium alginate, potassium alginate or ammonium alginate.

3. The formulation of claim 1 wherein the divalent ions include calcium and magnesium ions.

4. The formulation of claim 1 wherein the capsule is composed of HPMC, cellulose or gelatin.

5. The formulation of claim 1 wherein the digestive enzymes are selected from the group consisting of:

Alpha Galactosidase;

Amyloglucosidase;

Bacterial Alpha Amylase;

Beta Glucanase;

Cellulase;

Cellulase AN;

Amylase;

Fungal Lactase;

Yeast Lactas;

Hemicellulase;

Invertase;

Pectinase;

Xylanase;

Bromelain Protease;

Fungal Protease;

Neutral Protease;

Papain Protease;

Peptidase Aspergillus oryza;

Lipase;

Lipase AN;

Phytase;

Pancreatin;

nattokinase; and

serrapeptase.

6. The formulation of claim 1 wherein the monovalent alginate is Algin-900 (TIC Gums) or Keltone HV (ISP).

7. The formulation of claim 1 wherein in the monovalent alginate the ratio of mannuronic acid to guluronic acid (M:

G ratio) is less than 1.

8. The formulation of claim 1 further including one or more of:

microcrystalline cellulose, silica, resistant starches and prebiotic carbohydrate.

9. The formulation of claim 8 wherein the prebiotic carbohydrate is inulin.

10. The formulation of claim 8 wherein the microcrystalline cellulose is Avicel PH112 (FMC).

11. The formulation of claim 8 wherein the silica is in the form of Syloid 63 FP (WR Grace).

12. The formulation of claim 1 wherein the Syloid 63 FP is 1-2% of the formulation.

13. The formulation of claim 8 further including magnesium stearate.

14. The formulation of claim 13 wherein the magnesium stearate is 1-2% of the formulation.

21. The formulation of claim 1 or 15, wherein the monovalent alginates have total moisture contents in the range of 8-15%.

22. The formulation of claim 21 wherein the monovalent alginates are dried, before adding them to the formulation, to below 6% total moisture content.

23. The formulation of claim 22 wherein the monovalent alginates are dried without denaturing the alginate polymeric structure.

24. The formulation of claim 23 wherein the monovalent alginates are dried using vacuum drying, at a temperature below that causing denaturation, or infrared convection drying.

25. The formulation of claim 1 or 15, packaged in amber glass bottles or hermetically sealed foil packages.

26. The formulation of claim 25 wherein the packaging further includes moisture and oxygen absorption packets.

15. A formulation for administration to aid in digestion, comprising:

a capsule containing digestive enzymes, a monovalent alginate, and a buffering agent that does not react with the digestive enzymes or the monovalent alginate.

16. The formulation of claim 15 wherein the buffers do not generate significant quantities of divalent ions on exposure to aqueous solution.

17. The formulation of claim 16 wherein the buffers do not include salts of calcium or magnesium.

18. The formulation of claim 16 wherein the buffers do not generate significant quantities of carbonate or bicarbonate ions on exposure to aqueous solution.

19. The formulation of claim 15 wherein the buffers include sodium, potassium or ammonium salts of glycerol phosphate, including Glycerol phosphate disodium salt from Sigma.

20. The formulation of claim 19 wherein the sodium, potassium or ammonium salts of glycerol phosphate are mixed with the digestive enzymes and the monovalent alginate.

27. A kit comprising:

a capsule containing digestive enzymes, a monovalent alginate, and wherein the capsule is designed to not include compounds which would generate significant quantities of divalent ions, and thereby convert the monovalent alginate to significant quantities of a divalent alginate, when exposed to aqueous solution; and

a chelating agent which binds divalent ions in a tablet or secondary capsule.

28. The kit of claim 27 wherein the secondary capsule or tablet includes 250-1500 mg of chelating agent.

29. The kit of claim 28 wherein the chelating agent is EDTA, sodium hexametaphosphate, tetrasodium pyrophosphate or sodium citrate 19.

30. The kit of claim 27 wherein the monovalent alginate is sodium alginate, potassium alginate or ammonium alginate.

31. The kit of claim 27 wherein the divalent ions include calcium and magnesium ions.

32. The kit of claim 27 wherein the capsule is composed of HPMC, cellulose or gelatin.

33. The kit of claim 27 wherein the digestive enzymes are selected from the group consisting of:

Alpha Galactosidase;

Amyloglucosidase;

Bacterial Alpha Amylase;

Beta Glucanase;

Cellulase;

Cellulase AN;

Amylase;

Fungal Lactase;

Yeast Lactas;

Hemicellulase;

Invertase;

Pectinase;

Xylanase;

Bromelain Protease;

Fungal Protease;

Neutral Protease;

Papain Protease;

Peptidase Aspergillus oryza;

Lipase;

Lipase AN;

Phytase;

Pancreatin;

nattokinase; and

serrapeptase.

34. The kit of claim 27 wherein the monovalent alginate is Algin-900 (TIC Gums) or Keltone HV (ISP).

35. The kit of claim 27 wherein in the monovalent alginate the ratio of mannuronic acid to guluronic acid (M:

G ratio) is less than 1.

36. The kit of claim 27 further including one or more of:

microcrystalline cellulose, silica, resistant starches and prebiotic carbohydrate.

37. The kit of claim 36 wherein the prebiotic carbohydrate is inulin.

38. The kit of claim 36 wherein the microcrystalline cellulose is Avicel PH212 (FMC).

39. The kit of claim 36 wherein the silica is in the form of Syloid 63 FP (WR Grace).

40. The formulation of claim 39 wherein the Syloid 63 FP is 1-2% of the formulation.

41. The kit of claim 27 further including magnesium stearate.

42. The kit of claim 41 wherein the magnesium stearate is 1-2% of the formulation.

43. The kit of claim 27 further including a buffering agent that does not react with the digestive enzymes or the monovalent alginate.

44. The kit of claim 43 wherein the buffering agents do not generate significant quantities of divalent ions on exposure to aqueous solution.

45. The kit of claim 44 wherein the buffering agents do not include significant quantities of salts of calcium or magnesium.

46. The kit of claim 45 wherein the buffering agents do not generate significant quantities of carbonate or bicarbonate ions on exposure to aqueous solution.

47. The kit of claim 46 wherein the buffering agents include sodium, potassium or ammonium salts of glycerol phosphate.

48. The kit of claim 47 wherein the sodium, potassium or ammonium salts of glycerol phosphate are mixed with the digestive enzymes and the monovalent alginate.

49. The kit of claim 27, wherein the monovalent alginates have total moisture contents in the range of 8-15%.

50. The kit of claim 49 wherein the monovalent alginates are dried, before adding them to the formulation, to below 6% total moisture content.

51. The kit of claim 50 wherein the monovalent alginates are dried without denaturing the alginate polymeric structure.

52. The kit of claim 51 wherein the monovalent alginates are dried using vacuum drying, at a temperature below that causing denaturation, or infrared convection drying.

53. The kit of claim 27 packaged in amber glass bottles or hermetically sealed foil packages.

54. The kit of claim 27 wherein the packaging further includes moisture and oxygen absorption packets.