Hyperbranched polymeric micelles for encapsulation and delivery of hydrophobic molecules

• US 6,497,895 B2
• Filed: 10/09/2001
• Issued: 12/24/2002
• Est. Priority Date: 04/23/1999
• Status: Expired due to Fees

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Uhrich, Kathryn E.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/974,218
• Publication Number:
  US 20020035217A1
• Time in Patent Office: 441 Days
• Field of Search: 424/422, 424/450, 424/451, 424/78.08, 514/937, 514/969
• US Class Current: 424/422
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: C08G 83/005 Hyperbranched macromolecules
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: G03C 1/04 with macromolecular additives; with layer-forming substances
• CPC Class Codes: G03C 5/3056 Macromolecular additives G03C5/261 takes precedence

Abstract

Polymeric micelles for encapsulation of hydrophobic molecules are provided. Methods and formulations for delivering hydrophobic molecules to a host via these micelles are also provided. Methods of stabilizing liposomes or lipid based formulations by addition of polymeric micelles are also provided.

Claims

1. A transdermal device for the controlled release of a biologically or pharmaceutically active agent to the skin or mucosa of an animal, said device comprising a laminate of:

a. a reservoir layer having a first surface and a second surface, and having an encapsulate of a hydrophobic molecule encapsulated in a polymer, said polymer having a structure selected from the group consisting of;

2. The device of claim 1, wherein said backing layer comprises one or more layers of an occlusive material.

3. The device of claim 1, wherein R(—

O—

)_x is obtained from an aliphatic polyol having from 1 to 10 carbon atoms.

4. The device of claim 1, wherein R(—

O—

)_x is obtained from a cycloaliphatic polyol.

5. The device of claim 4, wherein the cycloaliphatic polyol is a sugar.

6. The device of claim 1, wherein R(—

O—

)_x is obtained from an aromatic polyol.

7. The device of claim 6, wherein the aromatic polyol is 1,1,1-tris(4′

-hydroxyphenyl)ethane, (1,3-adamantanediyl)diphenol, 2,6-bis(hydroxyalkyl)cresol, 2,2′

-alkylene-bis(6-tert-butyl-4-alkylphenol), 2-2′

-alkylene-bis(t-butylphenol), catechol, an alkylcatechol, pyrogallol, fluoroglycinol, 1,2,4-benzenetriol, resorcinol, an alkylresorcinol, a dialkylresorcinol, orcinol monohydrate, olivetol, hydroquinone, an alkylhydroquinone, 1,1-bi-2-naphthol, a phenyl hydroquinone, a dihydroxynaphthalene, 4,4′

-(9-fluorenylidene)-diphenol, anthrarobin, dithranol, bis(hydroxyphenyl) methane a biphenol, a dialkylstilbesterol, a bis(hydroxyphenyl) alkane, or bisphenol-A.

8. The device of claim 1, wherein R(—

O—

)_x is obtained from a hydroxylated crown ether, a cyclodextrin, or a dextrin.

9. The device of claim 1, wherein the polymer has a number average molecular weight between about 1,000 and about 100,000 daltons.

10. The device of claim 1, wherein the polymer has a number average molecular weight between about 2,500 and about 25,000 daltons.

11. A method of stabilizing a liposome or lipid-based formulation comprising adding to the liposome or lipid-based formulation a polymer, said polymer having a structure selected from the group consisting of:

12. The method of claim 11, wherein R(—

O—

)_x is obtained from an aliphatic polyol having from 1 to 10 carbon atoms.

13. The method of claim 11, wherein R(—

O—

)_x is obtained from a cycloaliphatic polyol.

14. The method of claim 13, wherein the cycloaliphatic polyol is a sugar.

15. The method of claim 11, wherein R(—

O—

)_x is obtained from an aromatic polyol.

16. The method of claim 15, wherein the aromatic polyol is 1,1,1-tris(4′

-hydroxyphenyl)ethane, (1,3-adamantanediyl)diphenol, 2,6-bis(hydroxyalkyl)cresol, 2,2′

-alkylene-bis(6-tert-butyl-4-alkylphenol), 2-2′

-alkylene-bis(t-butylphenol), catechol, an alkylcatechol, pyrogallol, fluoroglycinol, 1,2,4-benzenetriol, resorcinol, an alkylresorcinol, a dialkylresorcinol, orcinol monohydrate, olivetol, hydroquinone, an alkylhydroquinone, 1,1-bi-2-naphthol, a phenyl hydroquinone, a dihydroxynaphthalene, 4,4′

-(9-fluorenylidene)-diphenol, anthrarobin, dithranol, bis(hydroxyphenyl) methane a biphenol, a dialkylstilbesterol, a bis(hydroxyphenyl) alkane, or bisphenol-A.

17. The method of claim 11, wherein R(—

O—

)_x is obtained from a hydroxylated crown ether, a cyclodextrin, or a dextrin.

18. The method of claim 11, wherein the polymer has a number average molecular weight between about 1,000 and about 100,000 daltons.

19. The method of claim 11, wherein the polymer has a number average molecular weight between about 2,500 and about 25,000 daltons.