Pharmaceutical composition and method of intranasal administration

• US 5,112,804 A
• Filed: 09/14/1989
• Issued: 05/12/1992
• Est. Priority Date: 04/01/1987
• Status: Expired due to Term

• Current Assignee: Temple University of The Commonwealth System of Higher Education
• Original Assignee: Temple University of The Commonwealth System of Higher Education
• Inventors: Kowarski, Hanna R.
• Primary Examiner(s): Moezie, F. T.
• Application Number:
  US07/407,373
• Time in Patent Office: 971 Days
• Field of Search: 514/3, 514/4, 514/12-15, 514/947, 514/970, 424/434
• US Class Current: 514/5.9
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/28 Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• CPC Class Codes: A61K 9/0043 Nose

Abstract

A composition and method for nasal administration of pharmaceuticals utilizes glycyrrhetinic acid as an absorption enhancer. The composition comprises an effective amount of the pharmaceutically active substance, glycyrrhetinic acid, in an amount effective for enhancing permeation of the active substance across the nasal membrane, and a basic salt of an amino acid as an adjuvant. The composition may be administered to the nasal cavity in the form of a spray by using an atomizer, nebulizer, spayer, dropper or other device which ensures contact of the composition with the nasal mucus membrane.

Claims

1. In a composition for the intranasal administration of a pharmaceutically active substance containing an effective amount of said pharmaceutically active substance, the improvement comprising the inclusion of glycyrrhetinic acid in an amount effective for enhancing permeation of said active substance across the nasal membrane, and a basic salt of an amino acid as an adjuvant,

2. A composition according to claim 1 wherein the glycyrrhetinic acid comprises 18α

-glycyrrhetinic acid, 18β

-glycyrrhetinic acid, or mixtures thereof.

3. A composition according to claim 2 wherein the amino acid basic salt is selected from the group consisting of sodium and potassium salts of glycine, aspartic acid and glutamic acid.

4. A compound according to claim 2 further containing a polyhydric alcohol.

5. A composition according to claim 4 wherein the polyhydric alcohol comprises glycerin.

6. A composition according to claim 4 wherein the polyhydric alcohol comprises propylene glycol.

7. A composition according to claim 2 containing from about 0.25% (w/v) to about 1.5% (w/v) glycyrrhetinic acid.

8. A composition according to claim 7 containing from about 0.5% (w/v) to about 1.0% (w/v) glycyrrhetinic acid.

9. A composition according to claim 2 containing from about 1 to about 5 moles of amino acid basic salt per mole of glycyrrhetinic acid.

10. A composition according to claim 2 wherein the pharmaceutically active substance comprises a peptide or a polypeptide.

11. A composition according to claim 10 wherein the pharmaceutically active substance comprises insulin.

12. A composition according to claim 10 wherein the pharmaceutically active substance comprises growth hormone.

13. A composition according to claim 10 wherein the pharmaceutically active substance comprises glucagon.

14. A composition according to claim 10 wherein the pharmaceutically active substance comprises adrenocorticotropic hormone.

15. A composition according to claim 10 wherein the pharmaceutically active substance comprises chorionic gonadotropin.

16. A composition-according to claim 2 wherein the pharmaceutically active substance comprises vitamin B-12.

17. An aqueous insulin solution for intranasal administration comprising an effective amount of insulin, glycyrrhetinic acid in an amount effective for enhancing permeation of said insulin across the nasal mucosa, and a basic salt of an amino acid as an adjuvant for dissolving said glycyrrhetinic acid.

18. An aqueous insulin solution according to claim 17 wherein the glycyrrhetinic acid comprises 18α

-glycyrrhetinic acid or 18β

-glycyrrhetinic acid, or mixtures thereof.

19. An aqueous insulin solution according to claim 18 wherein the concentration of glycyrrhetinic acid is from about 0.25% (w/v) to about 1.5% (w/v).

20. An aqueous insulin solution according to claim 19 wherein the concentration of glycyrrhetinic acid is from about 0.5% (w/v) to about 1.0% (w/v).

21. An aqueous insulin solution according to claim 20 wherein the glycyrrhetinic acid is 18β

-glycyrrhetinic acid.

22. An aqueous insulin solution according to claim 21 additionally containing a polyhydric alcohol in an amount effective to increase the solubility of glycyrrhetinic acid in said composition.

23. An aqueous insulin solution according to claim 22 wherein the amino acid basic salt is selected from the group consisting of sodium and potassium salts of glycine, aspartic acid and glutamic acid.

24. A method for treatment of diabetes mellitus which comprises administering through the nasal mucous membrane of a patient suffering from diabetes an aqueous insulin solution according to claim 17.

25. A method for administering a pharmaceutically active agent which comprises administering such agent by permeation across the nasal membrane of an animal or human in combination with a permeation-enhancing amount of glycyrrhetinic and a basic salt of an amino acid acid.

26. A method according to claim 25 wherein the glycyrrhetinic acid comprises 18α

-glycyrrhetinic acid, 18β

-glycyrrhetinic acid, or mixtures thereof.

27. A method according to claim 26 for administering insulin.

28. A method according to claim 26 for administering growth hormone.

29. A method according to claim 26 for administering glucagon.

30. A method according to claim 26 for administering adrenocorticotropic hormone.

31. A method according to claim 26 for administering chorionic gonadotropin.

32. A method according to claim 26 for administering vitamin B-12.