Use of fatty acid esters as bioadhesive substances

• US 6,228,383 B1
• Filed: 06/05/1995
• Issued: 05/08/2001
• Est. Priority Date: 03/30/1994
• Status: Expired due to Term

• Current Assignee: GS Development AB (Per Gunnar Sandberg,)
• Original Assignee: GS Development AB (Per Gunnar Sandberg,)
• Inventors: Hansen, Jens, Nielsen, Lise Sylvest, Norling, Tomas
• Primary Examiner(s): MacMillan, Keith D.
• Application Number:
  US08/462,222
• Time in Patent Office: 2,164 Days
• Field of Search: 424/649, 424/407, 514/558, 514/559, 514/560
• US Class Current: 424/407
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/1274 Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5078 with drug-free core

Abstract

Use of fatty acid esters as bioadhesive substances. The fatty acid esters have molecular weights below about 1000 dalton and the fatty acid component of the fatty acid ester is a saturated or unsaturated fatty acid having a total number of carbon atoms of from C₈ to C₂₂. Particularly suitable fatty acid esters for use according to the invention are fatty acid esters which are selected from the group consisting of fatty acid esters of polyhydric alcohols, fatty acid esters of hydroxycarboxylic acids, fatty acid esters of monosaccharides, fatty acid esters of glycerylphosphate derivatives, fatty acid esters of glycerylsulfate derivative, and mixtures thereof. Excellent bioadhesive properties have been observed for fatty acid esters are glyceryl monooleate, glyceryl monolinoleate or glyceryl monolinolenate. Methods are described for administering an active or protective substance to undamaged or damaged skin or mucosa of an animal such as a human by combining the active or protective substance with a bioadhesive fatty acid ester. The mucosa may be the oral, aural, nasal, lung, gastrointestinal, vaginal, or rectal mucosa. The administration may also be to body cavities such as the oral cavity, e.g. via buccal administration.

Claims

1. A method of using fatty acid esters as bioadhesive substances for administering substances selected from the group consisting of active substances, protective substances, and mixtures thereof, the method comprising applying a bioadhesive composition to a portion of an animal or human body selected from the group consisting of oral, nasal, rectal, aural and vaginal mucosa, said bioadhesive composition comprising at least one substance selected from the group consisting of active substances, protective substances, and mixtures thereof, and at least 6% w/w, calculated on the composition, of at least one bioadhesive substance selected from the group consisting of fatty acid esters and mixtures of fatty acid esters.

2. A method according to claim 1, wherein the composition is applied to a mucosal site of the animal or human body at which it is subject to at least one of mechanical clearance or fluid clearance influence.

3. A method according to claim 1, wherein said bioadhesive composition is applied to one of a damaged or inflamed mucosa of the animal or human body.

4. A method according to claim 1, wherein the fatty acid component of the fatty acid ester is a fatty acid selected from the group consisting of a saturated and unsaturated fatty acid having a total number of carbon atoms of from C₈ to C₂₂.

5. A method according to claim 4, wherein the fatty acid component of said fatty acid ester is a saturated fatty acid moiety selected from the group consisting of caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, and behenic acid.

6. A method according to claim 4, wherein the fatty acid component of said fatty acid ester is an unsaturated fatty acid moiety selected from the group consisting of palmitoleic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid.

7. A method according to claim 1, wherein the fatty acid ester is selected from the group consisting of fatty acid esters of polyhydric alcohols, fatty acid esters of hydroxycarboxylic acids, fatty acid esters of monosaccharides, fatty acid esters of glycerylphosphate derivatives, fatty acid esters of glycerylsulfate derivatives, and mixtures thereof.

8. A method according to claim 7, wherein the polyhydric alcohol is selected from the group consisting of glycerol, 1,2-propanediol, 1,3-propanediol, diacylgalactosylglycerol, diacyldigalactosylglycerol, erythritol, xylitol, adonitol, arabitol, mannitol, and sorbitol.

9. A method according to claim 7, wherein the fatty acid ester is selected from the group consisting of glycerylmonooleate, glycerylmonolinoleate, glycerolmonolinolenate, and mixtures thereof.

10. A method according to claim 7, wherein the hydroxycarboxylic acid is selected from the group consisting of malic acid, tartaric acid, citric acid, and lactic acid.

11. A method according to claim 7, wherein the fatty acid ester is a fatty acid monoester of citric acid.

12. A method according to claim 7, wherein the monosaccharide is selected from the group consisting of glucose, mannose, fructose, threose, gulose, arabinose, ribose, erythrose, lyxose, galactose, sorbose, altrose, tallose, idose, rhamnose, and allose.

13. A method according to claim 7, wherein the fatty acid ester is a fatty acid monoester of a monosaccharide selected from the group consisting of sorbose, galactose, ribose, and rhamnose.

14. A method according to claim 7, wherein the glycerylphosphate derivative is a phospholipid selected from the group consisting of phospatidic acid, phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositole, and diphosphatidylglycerol.

15. A method according to claim 7, wherein the fatty acid ester is a fatty acid ester of a glycerylphosphate derivative or a glycerylsulfate derivative, and the fatty acid component is selected from the group consisting of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and behenic acid.

16. A method according to claim 7, wherein the fatty acid ester is selected form the group consisting of dioleoyl phosphatidylcholin, dilauroyl phosphatidylcholin, dimyristoyl phosphatidylcholin, dipalmitoyl phosphatidylcholin, distearoyl phosphatidylcholin, dibehenoyl phosphatidylcholin, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, dioleoyl phosphatidylglycerol, dilauroyl phosphatidylglycerol, dimyristoyl phosphatidylglycerol, dipalmitoyl phosphatidylglycerol, distearoyl phosphatidylglycerol, dipalmitoyl phosphatidic acid and mixtures thereof.

17. A method according to claim 1, wherein said fatty acid ester or mixture of fatty acid esters forms a fluid crystalline phase when contacted with an aqueous medium.

18. A method according to claim 1, wherein the composition is adapted for use as one of a pharmaceutical, cosmetic, veterinary, or agrochemical composition.

19. A method according to claim 1, wherein said fatty acid ester or mixture of fatty acid esters is present in a concentration of at least about 15% w/w, calculated on the composition.

20. A method according to claim 1, wherein said fatty acid ester or mixture of fatty acid esters is present in a concentration of at the most 95% w/w, calculated on the composition.

21. A method according to claim 1, wherein said fatty acid ester or mixture of fatty acid esters is present in a concentration of at the most 80% w/w, calculated on the composition.

22. A method according to claim 1, wherein contact of the composition with an aqueous medium results in formation of a fluid crystalline phase.

23. A method according to claim 1, wherein the composition further comprises a pharmaceutically acceptable excipient.

24. A method according to claim 1, wherein the composition is in the form of a spray.