Mucosal formulation

• US 20070264206A1
• Filed: 05/11/2006
• Published: 11/15/2007
• Est. Priority Date: 05/11/2006
• Status: Active Grant

• Current Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Original Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Inventors: Boga, Rameshbabu, Johnson, Robert
• Granted Patent: US 8,703,179 B2
• Time in Patent Office: Days
• US Class Current: 424/57
• 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 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

A mucosal formulation for administration to mucosal membranes, such as in the mouth, nasal passage, stomach, vagina, etc., is disclosed. The mucosal formulation contains a lipid-pharmaceutical agent complex formed from phospholipids possessing a hydrophobic moiety that orients into a hydrophobic phase and a polar head moiety that orients towards the aqueous phase (i.e., “amphipathic” lipids). When placed in an aqueous medium (e.g., vaginal fluid), the phospholipids form liposomes or other small lipid vesicles (e.g., micelles) that may then be used to deliver pharmaceutical agents into a living organism.

Claims

1. A method for promoting mucosal health, the method comprising administering a mucosal formulation to a mucosal membrane, the mucosal formulation comprising a complex that includes a phospholipid and pharmaceutical agent, wherein the phospholipid is formed from an alkyl phosphocholine.

2. The method of claim 1, wherein the alkyl phosphocholine has the following structure:

R₁, R₂, and R₃ are independently selected from the group consisting of hydrogen or C₁ to C₆ alkyl groups that are linear or branched, saturated or unsaturated, substituted or unsubstituted;

R₄ is selected from the group consisting of C₁ to C₄₀ alkyl groups that are linear or branched, saturated or unsaturated, substituted or unsubstituted;

X is O, S, or NH;

y is from 1 to 10;

z is from 0 to 40; and

n is from 1 to 40.

3. The method of claim 2, wherein n is from 4 to 24.

4. The method of claim 1, wherein the alkyl phosphocholine is selected from the group consisting of hexadecyl thiophosphocholine, tetradecyl phosphocholine, hexadecyl phosphocholine, docosanoyl phosphocholine, 1,2-dihexadecyl-rac-glycero-3-phosphocholine, and DL-α

-lysophosphatidylcholine-r-o-hexadecyl.

5. The method of claim 4, wherein the alkyl phosphocholine is hexadecyl phosphocholine.

6. The method of claim 1, wherein phospholipids constitute from about 0.01 to about 1000 micrograms per milliliter of the mucosal formulation.

7. The method of claim 1, wherein phospholipids constitute from about 0.1 to about 100 micrograms per milliliter of the mucosal formulation.

8. The method of claim 1, wherein phospholipids constitute from about 0.2 to about 10 micrograms per milliliter of the mucosal formulation.

9. The method of claim 1, wherein phospholipids constitute from about 0.5 to about 5 micrograms per milliliter of the mucosal formulation.

10. The method of claim 1, wherein the phospholipid inhibits the growth of Candida albicans.

11. The method of claim 1, wherein the phospholipid inhibits the growth of Staphyloccus aureus.

12. The method of claim 1, wherein the phospholipid inhibits the growth of Gardnerella vaginale.

13. The method of claim 1, wherein the phospholipid inhibits the growth of Candida albicans, Staphyloccus aureus, Gardnerella vaginale, or combinations thereof without substantially inhibiting the growth of Lactobacillus acidophilus.

14. The method of claim 1, wherein the pharmaceutical agent is a non-androgenic steroid selected from the group consisting of progestins, estrogens, and combinations thereof.

15. The method of claim 14, wherein the pharmaceutical agent is estradiol or an ester thereof.

16. The method of claim 1, wherein the complex is in the form of a vesicle.

17. The method of claim 16, wherein the vesicle is a liposome or micelle.

18. The method of claim 1, wherein the pharmaceutical agent is controllably or sustainably delivered over a period of time of from about 2 to about 240 hours.

19. The method of claim 1, wherein the vaginal formulation comprises a pharmaceutically acceptable excipient.

20. The method of claim 1, wherein the complex becomes hydrated upon administration.

21. The method of claim 1, wherein the mucosal membrane is located in the vagina of a female.

22. A mucosal formulation comprising a vesicle that includes a phospholipid and pharmaceutical agent, the phospholipid being formed from an alkyl phosphocholine having the following structure:

R₁, R₂, and R₃ are independently selected from the group consisting of hydrogen or C₁ to C₆ alkyl groups that are linear or branched, saturated or unsaturated, substituted or unsubstituted;

R₄ is selected from the group consisting of C₁ to C₄₀ alkyl groups that are linear or branched, saturated or unsaturated, substituted or unsubstituted;

X is O, S, or NH;

y is from 2 to 4;

z is from 0 to 40; and

n is from 4 to 24.

23. The mucosal formulation of claim 22, wherein the alkyl phosphocholine is selected from the group consisting of hexadecyl thiophosphocholine, tetradecyl phosphocholine, hexadecyl phosphocholine, docosanoyl phosphocholine, 1,2-dihexadecyl-rac-glycero-3-phosphocholine, and DL-α

-lysophosphatidylcholine-r-o-hexadecyl.

24. The mucosal formulation of claim 22, wherein the alkyl phosphocholine is hexadecyl phosphocholine.

25. The mucosal formulation of claim 22, wherein phospholipids constitute from about 0.01 to about 1000 micrograms per milliliter of the mucosal formulation.

26. The mucosal formulation of claim 22, wherein phospholipids constitute from about 0.1 to about 100 micrograms per milliliter of the mucosal formulation.

27. The mucosal formulation of claim 22, wherein the pharmaceutical agent is a non-androgenic steroid selected from the group consisting of progestins, estrogens, and combinations thereof.

28. The mucosal formulation of claim 22, wherein the vesicle is dehydrated.

29. The mucosal formulation of claim 22, wherein the formulation is in the form of a gel.