Mucosal formulation
View Patent ↗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.
1. A vaginal formulation comprising a dehydrated vesicle that consists of a phospholipid, a pharmaceutical agent, and a protecting sugar, the phospholipid being formed from an alkyl phosphocholine that comprises hexadecyl thiophosphocholine, tetradecyl phosphocholine, hexadecyl phosphocholine, docosanoyl phosphocholine, or a combination thereof, and the pharmaceutical agent including estradiol or an ester thereof.
2. The vaginal formulation of claim 1 , wherein the alkyl phosphocholine is hexadecyl phosphocholine.
3. The vaginal formulation of claim 1 , wherein phospholipids constitute from about 001 to about 1000 micrograms per milliliter of the vaginal formulation.
4. The vaginal formulation of claim 1 , wherein phospholipids constitute from about 0.1 to about 100 micrograms per milliliter of the vaginal formulation.
5. The vaginal formulation of claim 1 , wherein the pharmaceutical agent is a non-androgenic steroid selected from the group consisting of progestins, estrogens, and combinations thereof.
6. The vaginal formulation of claim 1 , wherein the molar ratio of the phospholipid to the pharmaceutical agent is from about 3:1 to about 100:1.
7. A method for moisturizing and inhibiting the growth of microorganisms in a vagina of a female, the method comprising intravaginally administering a vaginal formulation so that the formulation is placed into contact with vaginal fluid in the vagina, the formulation comprising a vesicle that has been dehydrated in the presence of a protecting sugar, wherein the vesicle consists of the protecting sugar and a complex that inhibits the growth of Candida albicans , wherein the complex consists of a phospholipid and pharmaceutical agent, wherein the phospholipid is formed from an alkyl phosphocholine having the following structure:
R 1 , R 2 , and R 3 are independently selected from the group consisting of hydrogen or C 1 to C 6 alkyl groups that are linear or branched, saturated or unsaturated, substituted or unsubstituted;
R 4 is an unsubstituted C 1 to C 40 alkyl group;
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,
wherein the pharmaceutical agent s released upon contacting the formulation with the vaginal fluid.
8. The method of claim 7 , wherein n is from 4 to 24.
9. The method of claim 7 , wherein the alkyl phosphocholine is selected from the group consisting of hexadecyl thiophosphocholine, tetradecyl phosphocholine, hexadecyl phosphocholine, docosanoyl phosphocholine, and combinations thereof.
10. The method of claim 7 , wherein the alkyl phosphocholine is hexadecyl phosphocholine.
11. The method of claim 7 , wherein phospholipids constitute from about 0.01 to about 1000 micrograms per milliliter of the formulation.
12. The method of claim 7 , wherein phospholipids constitute from about 0.1 to about 100 micrograms per milliliter of the formulation.
13. The method of claim 7 , wherein phospholipids constitute from about 0.2 to about 10 micrograms per milliliter of the formulation.
14. The method of claim 7 , wherein phospholipids constitute from about 0.5 to about 5 micrograms per milliliter of the formulation.
15. The method of claim 7 , wherein the complex also inhibits the growth of Staphylococcus aureus.
16. The method of claim 7 , wherein the complex also inhibits the growth of Gardnerella vaginale.
17. The method of claim 7 , wherein the complex inhibits the growth of Candida albicans, Staphylococcus aureus, Gardnerella vaginale , or combinations thereof without substantially inhibiting the growth of Lactobacillus acidophilus.
18. The method of claim 7 , wherein the pharmaceutical agent is a non-androgenic steroid selected from the group consisting of progestins, estrogens, and combinations thereof.
19. The method of claim 18 , wherein the pharmaceutical agent is estradiol or an ester thereof.
20. The method of claim 7 , wherein the vesicle is a liposome or micelle.
21. The method of claim 7 , wherein the pharmaceutical agent is controllably or sustainably delivered over a period of time of from about 2 to about 240 hours.
22. The method of claim 7 , wherein the complex becomes hydrated upon administration.