COMPOSTIONS AND METHODS FOR IONTOPHORESIS DELIVERY OF ACTIVE INGREDIENTS THROUGH HAIR FOLLICLES

• US 20080193514A1
• Filed: 10/30/2007
• Published: 08/14/2008
• Est. Priority Date: 11/02/2006
• Status: Abandoned Application

• Current Assignee: Hokkaido University, Transcu Ltd.
• Original Assignee: Hokkaido University, Transcu Ltd.
• Inventors: Yamamoto, Masahiko, Kogure, Kentaro, Harashima, Hideyoshi
• Application Number:
  US11/929,451
• Publication Number:
  US 20080193514A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/0448 Drug reservoir

Abstract

Systems, devices, and methods for delivering one or more active ingredients to deep regions of hair follicles and intradermal tissues in the vicinity of hair follicles. In some embodiments, a composition is provided including an active ingredient carried in a liposome. The liposome includes a cationic lipid and an amphiphilic glycerophospholipid having a saturated fatty acid moiety and unsaturated fatty acid moiety.

Claims

1. A composition for administering an active ingredient through a hair follicle to a living body by iontophoresis, comprising:

a plurality of liposomes comprising;

a cationic lipid, and

an amphiphilic glycerophospholipid, the amphiphilic glycerophospholipid having a saturated fatty acid moiety and an unsaturated fatty acid moiety; and

an active ingredient carried by the liposome.

2. The composition according to claim 1 wherein the cationic lipid is a C_1-20 alkane substituted with a C_1-22 acyloxy group and a triC_1-6 alkylammonium group.

3. The composition according to claim 1 wherein the cationic lipid comprises two C_1-22 acyloxy groups and one triC_1-6 alkylammonium group.

4. The composition according to claim 1 wherein the cationic lipid is 1,2-dioleoyloxy-3-(trimethylammonium)propane.

5. The composition according to claim 1 wherein the amphiphilic glycerophospholipid is phosphatidylcholine or an egg-yolk phosphatidylcholine.

6. The composition according to claim 1, wherein the saturated fatty acid moiety is a C_12-22 saturated fatty acid.

7. The composition according to claim 1 wherein the unsaturated fatty acid moiety is selected from the group consisting of palmitic acid, lauric acid, myristic acid, pentadecanoic acid, margaric acid, stearic acid, tuberculostearic acid, arachidic acid, and behenic acid.

8. The composition according to claim 1 wherein the unsaturated fatty acid moiety comprises 1, 2, 3, 4, 5 or 6 carbon-carbon unsaturated double bonds.

9. The composition according to claim 1 wherein the unsaturated fatty acid moiety is C_14-22 unsaturated fatty acid.

10. The composition according to claim 1 wherein the unsaturated fatty acid moiety is selected from the group consisting of oleic acid, myristoleic acid, palmitoleic acid, elaidic acid, vaccenic acid, gadoleic acid, erucic acid, nervonic acid, linolic acid, α

-linoleic acid, eleostearic acid, stearidonic acid, arachidonic acid, eicosapentaenoic acid, clupanodonic acid, and docosahexaenoic acid.

11. The composition according to claim 1, wherein a molar ratio of the cationic lipid to the amphiphilic glycerophospholipid is from about 3:

7 to about 7;

3.

12. The composition according to claim 1, wherein the liposome further comprises a sterol, the sterol present in a molar ratio of the cationic lipid to the sterol of from about 3:

7 to about 7;

3.

13. The composition according to claim 12 wherein the sterol is selected from the group consisting of cholesterol, C_12-31 cholesteryl fatty acid, C_12-31 dihydrocholesteryl fatty acid, polyoxyethylene cholesteryl ether, and polyoxyethylene dihydrocholesteryl ether.

14. The composition according to claim 12 wherein the sterol is selected from the group consisting of cholesterol, cholesteryl lanolate, cholesteryl oleate, cholesteryl nonanate, cholesteryl macadaminate, and polyoxyethylene dihydrocholesteryl ether.

15. The composition according to claim 12 wherein the sterol is cholesterol.

16. The composition according to claim 12 wherein a molar ratio of the amphiphilic glycerophospholipid to the sterol is from about 3:

7 to about 7;

3.

17. The composition according to claim 12 wherein a molar ratio of the cationic lipid to the total of the amphiphilic glycerophospholipid and the sterol is from about 3:

7 to about 7;

3.

18. The composition according to claim 12 wherein a molar ratio of the cationic lipid, to the amphiphilic glycerophospholipid, and to the sterol is about 2:

1;

1.

19. The composition according to claim 1 wherein an average particle diameter of the liposome is about 400 nm or more.

20. The composition according to claim 1 wherein an average particle diameter of the liposome ranges from about 400 nm to about 1000 nm.

21. The composition according to claim 1 wherein the active ingredient is selected from the group consisting of a drug, a colorant, a nucleic acid, a protein, an enzyme, a peptide, a lipopolysaccharide, and a cell component.

22. A method for iontophoretically administering one or more active ingredients to deep regions of hair follicles and/or intradermal tissues in the vicinity of hair follicles by iontophoresis, comprising:

providing a composition comprising a plurality of liposomes having an average liposome diameter ranging from about 400 to about 1000 nm, the plurality of liposomes comprising a cationic lipid, an amphiphilic glycerophospholipid, and the one or more active ingredients, the amphiphilic glycerophospholipid having a saturated fatty acid moiety and an unsaturated fatty acid moiety, and the cationic lipid present in a molar ratio of the cationic lipid to the amphiphilic glycerophospholipid of about 3;

7 to about 7;

3; and

iontophoretically administering the composition to a living body by iontophoresis using a current ranging from about 0.1 mA/cm² to about 0.6 mA/cm².

23. The method according to claim 22, wherein providing a composition comprising the plurality of liposomes includes providing the amphiphilic glycerophospholipid having a C_12-22 saturated fatty acid moiety and a moiety is C_14-22 unsaturated fatty acid moiety.

24. The method according to claim 22, wherein the plurality of liposomes further comprise a sterol;

and wherein providing a composition comprising the plurality of liposomes includes providing the plurality of liposomes having the sterol present in a molar ratio of the cationic lipid to the sterol of about 3;

7 to about 7;

3.

25. The method according to claim 22, wherein the plurality of liposomes further comprise a sterol selected from the group consisting of cholesterol, C_12-31 cholesteryl fatty acid, C_12-31 dihydrocholesteryl fatty acid, polyoxyethylene cholesteryl ether, and polyoxyethylene dihydrocholesteryl ether;

and

wherein providing a composition comprising the plurality of liposomes includes providing the plurality of liposomes including the sterol present in a molar ratio of the cationic lipid to the sterol of about 3;

7 to about 7;

3.