Bile preparations for gastrointestinal disorders

• US 20060188530A1
• Filed: 03/10/2006
• Published: 08/24/2006
• Est. Priority Date: 07/24/1998
• Status: Active Grant

• Current Assignee: Seo Hong Yoo
• Original Assignee: Seo Hong Yoo
• Inventors: Yoo, Seo Hong
• Granted Patent: US 7,932,243 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• 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 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/554 the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present disclosure relates to methods and compositions to offset, ameliorate and/or alleviate one or more unwanted and/or adverse gastrointestinal effects. For example, in some embodiments, the present disclosure relates to compositions that include a bile acid, a carbohydrate and/or a pharmaceutical compound, wherein the pharmaceutical is associated with an adverse gastrointestinal effect in a subject (e.g., mammal or human). Non-limiting examples of pharmaceutical compounds may include a nonsteroidal anti-inflammatory drug, a gastric irritating drug (e.g., an antibiotic, an adrenal cortocoid steroid and an anti-cancer drug) and combinations thereof. The disclosure further relates to methods of ameliorating or eliminating at least one adverse gastrointestinal effects of a composition, comprising administering to a subject an aqueous solution comprising a bile acid and a carbohydrate.

Claims

1. A method of ameliorating or eliminating in a subject at least one adverse gastrointestinal effect of a composition, said method comprising:

administering the composition to the subject; and

administering to the subject an aqueous solution substantially free of precipitates or particles comprising;

(a) a first material selected from the group consisting of a bile acid, an aqueous soluble derivative of a bile acid, a bile acid salt, and a bile acid conjugated with an amine by an amide linkage;

(b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product or an aqueous soluble non-starch polysaccharide; and

(c) water, wherein the first material and the carbohydrate both remain in solution for all pH values obtainable in an aqueous system.

2. A method according to claim 1, wherein the composition comprises a compound selected from the group consisting of an alcohol, a non-steroidal anti-inflammatory drug, a gastric irritating drug, and combinations thereof.

3. A method according to claim 2, wherein the gastric irritating drug is selected from the group consisting of an antibiotic, an adrenal corticoid steroid, an anti-cancer drug, and combinations thereof.

4. A method according to claim 2, wherein the composition comprises a compound selected from the group consisting of ethanol, aspirin, methyl salicylate, diflunisal, indomethacin, sulindac, diclofenac, ibuprofen, ketoprofen, naproxen, ketorolac, mefenamic acid, piroxicam, meloxicam, coxibscelecoxib rofecoxib, valdecoxib, parecoxib, etoricoxib, nimesulide, aminoglutethimide, anastrazole, bicalutamide, chlorambucil, cyclophosphamide, cytarabine, diethyldithiocarbamate, dacarbazine, flutamide, letrozole, lomustine, mercaptopurine, methotrexate, nilutamide, plicamycin, procarbazine HCl, tacrolimus hydrate, cortisol, cortisone, prednisone, prednisolone, methylprednisolone, triamcinolone, fluprednisolone, bethamethasone, dexamethasone, fludrocortisone, desoxycorticosterone acetate, and combinations thereof.

5. A method according to claim 4, wherein the composition comprises up to 100% ethanol (w/w).

6. A method according to claim 4, wherein the composition comprises over about 20% ethanol (w/w).

7. A method according to claim 4, wherein the composition comprises less than about 20% ethanol (w/w).

8. A method according to claim 1, wherein the subject is a mammal.

9. A method according to claim 8, wherein the subject is a human.

10. A method according to claim 1, wherein the first material is present in a therapeutically effective amount.

11. A method according to claim 1, wherein the first material is selected from the group consisting of chenodeoxycholic acid, cholic acid, hyodeoxycholic acid, deoxycholic acid, 7-oxolithocholic acid, lithocholic acid, iododeoxycholic acid, iocholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycoursodeoxycholic acid, taurocholic acid, glycocholic acid, their derivatives at a hydroxyl or carboxylic acid group on the steroid nucleus, their salts, or their conjugates with amines.

12. A method according to claim 1, wherein the aqueous soluble starch conversion product is selected from the group consisting of maltodextrin, dextrin, liquid glucose, corn syrup solid, and soluble starch.

13. A method according to claim 1, wherein the pH is between about 1 and about 10.

14. A method according to claim 1, wherein the first material is ursodeoxycholic acid or a sodium salt of ursodeoxycholic acid.

15. A method according to claim 1, wherein the aqueous soluble starch conversion product comprises maltodextrin.

16. A method according to claim 1, wherein the aqueous soluble starch conversion product comprises corn syrup solid.

17. A method according to claim 1, wherein the aqueous soluble non-starch polysaccharide is selected from the group consisting of dextran, guar gum, pectin, indigestible soluble fiber.

18. A method according to claim 1, wherein said administering the composition follows said administering to the subject an aqueous solution.

19. A method according to claim 18, wherein said method further comprises preventing at least one adverse gastrointestinal effect of the composition.

20. A method according to claim 1, wherein said administering the composition precedes said administering to the subject an aqueous solution.

21. A method according to claim 1, wherein said administering the composition comprises administering the composition in a plurality of doses.

22. A method according to claim 21, wherein said administering the composition in a plurality of doses comprises administering at least one dose of the composition following said administering to the subject an aqueous solution.

23. A method according to claim 21, wherein said administering the composition in a plurality of doses comprises administering at least one dose of the composition before said administering to the subject an aqueous solution.

24. A method according to claim 1, wherein said administering to the subject an aqueous solution comprises administering the aqueous solution in a plurality of doses.

25. A method according to claim 24, wherein said administering to the subject an aqueous solution in a plurality of doses comprises administering at least one dose of the aqueous solution following said administering the composition.

26. A method according to claim 24, wherein said administering to the subject an aqueous solution in a plurality of doses comprises administering at least one dose of the aqueous solution before said administering the composition.

27. A method according to claim 1, wherein said administering the composition and said administering to the subject an aqueous solution are concurrently executed.

28. A method according to claim 1, wherein the adverse gastrointestinal effect comprises an adverse effect on the gastro duodenum.

29. A method according to claim 1, wherein the adverse gastrointestinal effect comprises an effect selected from the group consisting of gastroduodenal mucosal cell death, gastrointestinal necrosis, gastrointestinal apoptosis, gastroduodenal mucosal lesion, gastroduodenal mucosal erosion, gastroduodenal ulcer, gastrointestinal cancer, gastrointestinal bleeding, epigastralgia, gastritis, gastrointestinal redness, gastrointestinal edema, and combinations thereof.

30. An aqueous solution substantially free of precipitates or particles comprising:

(a) a first material selected from the group consisting of a bile acid, an aqueous soluble derivative of a bile acid, a bile acid salt, and a bile acid conjugated with an amine by an amide linkage;

(b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product or an aqueous soluble non-starch polysaccharide;

(c) a pharmaceutically effective amount of a pharmaceutical compound; and

(d) water,

wherein the first material and the carbohydrate both remain in solution for all pH values obtainable in an aqueous system and wherein the pharmaceutical compound has at least one adverse gastrointestinal effect when administered to a subject.

31. An aqueous solution according to claim 30, wherein the pharmaceutical compound is selected from the group consisting of an alcohol, a non-steroidal anti-inflammatory drug, a gastric irritating drug, and combinations thereof.

32. A method according to claim 31, wherein the gastric irritating drug is selected from the group consisting of an antibiotic, an adrenal corticoid steroid, an anti-cancer drug, and combinations thereof.

33. An aqueous solution according to claim 31, wherein the pharmaceutical compound is selected from the group consisting of ethanol, aspirin, methyl salicylate, diflunisal, indomethacin, sulindac, diclofenac, ibuprofen, ketoprofen, naproxen, ketorolac, mefenamic acid, piroxicam, meloxicam, coxibscelecoxib rofecoxib, valdecoxib, parecoxib, etoricoxib, nimesulide, aminoglutethimide, anastrazole, bicalutamide, chlorambucil, cyclophosphamide, cytarabine, diethyldithiocarbamate, dacarbazine, flutamide, letrozole, lomustine, mercaptopurine, methotrexate, nilutamide, plicamycin, procarbazine HCl, tacrolimus hydrate, cortisol, cortisone, prednisone, prednisolone, methylprednisolone, triamcinolone, fluprednisolone, bethamethasone, dexamethasone, fludrocortisone, desoxycorticosterone acetate, and combinations thereof.

34. An aqueous solution according to claim 30, wherein the subject is a mammal.

35. An aqueous solution according to claim 30, wherein the subject is a human.

36. An aqueous solution according to claim 30, wherein the first material is present in a therapeutically effective amount.

37. An aqueous solution according to claim 30, wherein the first material is selected from the group consisting of chenodeoxycholic acid, cholic acid, hyodeoxycholic acid, deoxycholic acid, 7-oxolithocholic acid, lithocholic acid, iododeoxycholic acid, iocholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycoursodeoxycholic acid, taurocholic acid, glycocholic acid, their derivatives at a hydroxyl or carboxylic acid group on the steroid nucleus, their salts, or their conjugates with amines.

38. An aqueous solution according to claim 30, wherein the aqueous soluble starch conversion product is selected from the group consisting of maltodextrin, dextrin, liquid glucose, corn syrup solid, and soluble starch.

39. An aqueous solution according to claim 30, wherein the first material is ursodeoxycholic acid or a sodium salt of ursodeoxycholic acid.

40. An aqueous solution according to claim 30, wherein the aqueous soluble starch conversion product comprises maltodextrin.

41. An aqueous solution according to claim 30, wherein the aqueous soluble starch conversion product comprises corn syrup solid.

42. An aqueous solution according to claim 30, wherein the aqueous soluble non-starch polysaccharide is selected from the group consisting of dextran, guar gum, pectin, indigestible soluble fiber.

43. An aqueous solution according to claim 30, wherein the aqueous solution is substantially free of cyclodextrin.

44. An aqueous solution according to claim 30, wherein the aqueous solution is substantially free of alcohol.

45. A method of ameliorating or eliminating in a subject at least one adverse gastrointestinal effect of a composition that is associated with at least one adverse gastrointestinal effect, said method comprising:

administering to the subject an aqueous solution substantially free of precipitates or particles comprising;

(a) a first material selected from the group consisting of a bile acid, an aqueous soluble derivative of a bile acid, a bile acid salt, and a bile acid conjugated with an amine by an amide linkage;

(b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product or an aqueous soluble non-starch polysaccharide; and

(c) water, wherein the first material and the carbohydrate both remain in solution for all pH values obtainable in an aqueous system,

wherein the subject has received or is likely to receive the composition that is associated with at least one adverse gastrointestinal effect.