Preparation of aqueous clear solution dosage forms with bile acids

• US 7,303,768 B2
• Filed: 02/05/2001
• Issued: 12/04/2007
• Est. Priority Date: 07/24/1998
• Status: Expired due to Fees

• Current Assignee: Seo Hong Yoo
• Original Assignee: Seo Hong Yoo
• Inventors: Yoo, Seo Hong
• Primary Examiner(s): SHIBUYA, MARK LANCE
• Application Number:
  US09/778,154
• Publication Number:
  US 20020031558A1
• Time in Patent Office: 2,493 Days
• Field of Search: 514/169, 514/60, 514/58, 514/59, 424/455, 424/456, 424/479, 424/435, 424/528
• US Class Current: 424/528
• 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 47/28 Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• 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 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Abstract

Compositions for pharmaceutical and other uses comprising clear aqueous solutions of bile acids which do not form any detectable precipitates over selected ranges of pH values of the aqueous solution and methods of making such solutions. The compositions of the invention comprise water; a bile acid in the form of a bile acid, bile acid salt, or a bile acid conjugated with an amine by an amide linkage; and either or both an aqueous soluble starch conversion product and an aqueous soluble non-starch polysaccharide. The composition remains in solution without forming a precipitate over a range of pH values and, according to one embodiment, remains in solution for all pH values obtainable in an aqueous system. The composition, according to some embodiments, may further contain a pharmaceutical compound in a pharmaceutically effective amount. Non-limiting examples of pharmaceutical compounds include insulin, heparin, bismuth compounds, amantadine and rimantadine.

Claims

1. An aqueous solution free of precipitates or particles comprising:

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

(ii) a second material selected from the group consisting of maltodextrin, dextrin, corn syrup, corn syrup solid, soluble starch, and dextrans, and combinations thereof;

(iii) at least one alkali, and

(iv) water,

wherein the first and second materials both remain in solution for all pH values obtainable in an aqueous system.

2. The solution of claim 1, wherein the solution is selected from the group consisting of a syrup and a thick syrup.

3. The solution of claim 1, wherein the bile acid portion of said first material is selected from the group consisting of ursodeoxycholic acid, chenodeoxycholic acid, cholic acid, hyodeoxycholic acid, deoxycholic acid, 7-oxolithocholic acid, lithocholic acid, iododeoxycholic acid, iocholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid, taurodeoxcycholic acid, glycoursodeoxycholie acid, tauroeholic acid, and glycocholic acid.

4. The solution of claim 1, wherein the solution comprises one or more additional bile acid salts and amine-conjugated bile acids conjugated by an amide linkage.

5. The solution of claim 1 further comprising an agent having anti-inflammatory activity.

6. The solution of claim 1 further comprising an agent having analgesic activity.

7. The solution of claim 1 further comprising an agent having anticonvulsant activity.

8. The solution of claim 1 further comprising an agent capable of prolonging survival time in hypoxic conditions.

9. The solution of claim 1 further comprising an agent capable of alleviating or ameliorating a condition selected from the group consisting of stomatitis, gingivoglossitis and toothache.

10. The solution of claim 1, wherein the aqueous solution is free of all precipitates or particles.

11. An aqueous solution free of precipitates or particles comprising:

(a) a first material selected from the group consisting of an ursodeoxycholic acid salt, an ursodeoxycholic acid conjugated with an amine by an amide linkage, and combinations thereof;

(b) a second material which is maltodextrin;

(c) at least one alkali, and

(d) water,

wherein the first and second materials both remain in solution for all pH values obtainable in an aqueous system and wherein the weight ratio of the second material to the first material is about 25;

1.

12. The solution of claim 11, wherein the aqueous solution is free of all precipitates or particles.

13. An aqueous solution free of precipitates or particles comprising:

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

(ii) a second material selected from the group consisting of maltodextrin, dextrin, corn syrup, corn syrup solid, soluble starch, and dextrans, and combinations thereof; and

(iii) water,

wherein the first and second materials both remain in solution for all pH values obtainable in an aqueous system.

14. The solution of claim 13, wherein the aqueous solution is free of all precipitates or particles.