Encapsulation of chemical compounds in fluorous-core and fluorous-inner-shell micelles formed from semifluorinated-block or fluorinated-block copolymers

• US 20050214379A1
• Filed: 01/03/2005
• Published: 09/29/2005
• Est. Priority Date: 01/02/2004
• Status: Abandoned Application

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Hoang, Khanh, Mecozzi, Sandro
• Application Number:
  US11/028,948
• Publication Number:
  US 20050214379A1
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 31/075 Ethers or acetals
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• 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 9/1273 Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances polymers grafted or coated on phosphatidyl liposomes A61K9/1271, on non-phosphatidyl liposomes A61K9/1272
• CPC Class Codes: A61K 9/1274 Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: C08F 293/005 using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent
• CPC Class Codes: C08F 297/00 Macromolecular compounds obtained by successively polymerising different monomer systems using a catalyst of the ionic or coordination type without deactivating the intermediate polymer
• CPC Class Codes: C08K 5/0008 Organic ingredients according to more than one of the "one dot" groups of C08K5/01 - C08K5/59
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 53/00 Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 53/005 Modified block copolymers

Abstract

In one embodiment of the present invention, a block copolymer with a hydrophilic region and a semifluorinated region is synthesized and mixed, below a critical micellar concentration, with a fluorinated drug, and the temperature then lowered, or the block-copolymer concentration then increased, or other solution conditions changed, in order to form fluorous-core, drug-encapsulating micelles. Alternatively, a drug may be taken up by already formed micelles in solution. A suspension of the fluorous-core, fluorinated-drug-encapsulating micelles is injected into the bloodstream to deliver the fluorinated drug to target tissues and organs. In an alternative embodiment of the present invention, a block copolymer with a hydrophilic block, a hydrophobic block, and a semifluorinated block is used to form fluorous-core, drug-encapsulating micelles. In a third embodiment, a block copolymer with a hydrophilic block, a semifluorinated block, and a hydrophobic block is used to form hydrophobic-core, drug-encapsulating micelles. In additional embodiments, block copolymers with various types of blocks are synthesized and employed to form micelles with interior shell and core regions suitable for encapsulating specific target compounds for a variety of purposes.

Claims

1. A fluorophilic-chemical-encapsulation system comprising:

a fluorophilic chemical compound; and

a supramolecular structure comprising a number of block-copolymer molecules, each block-copolymer molecule containing at least one of

a fluorinated block, and

a semifluorinated block.

2. The fluorophilic-chemical-encapsulation system of claim 1 wherein the fluorophilic chemical compound contains at least one fluorine atom.

3. The fluorophilic-chemical-encapsulation system of claim 1 wherein the fluorophilic chemical compound is a drug that contains at least one fluorine atom.

4. The fluorophilic-chemical-encapsulation system of claim 3 wherein the drug is sevoflurane.

5. The fluorophilic-chemical-encapsulation system of claim 1 wherein the supramolecular structure comprising a number of block-copolymer molecules is a fluorous-core micelle comprising one of:

polyethylene-glycol/semifluorinated-alkane block-copolymer molecules; and

polyethylene-glycol/fluorinated-alkane block-copolymer molecules.

6. The fluorophilic-chemical-encapsulation system of claim 5 wherein the block-copolymer molecules each includes a polyethylene glycol block containing between 20 and 300 ethoxy monomers.

7. The fluorophilic-chemical-encapsulation system of claim 5 wherein the block-copolymer molecules each include one of a semifluorinated alkane and fluorinated alkane having between 4 and 70 carbon atoms.

8. The fluorophilic-chemical-encapsulation system of claim 5 wherein the block-copolymer molecules are one of:

2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heneicosafluoro-1-undecanyl-poly(ethylene glycol) mono-methyl ether; and

2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-heptadecafluoro-1-nonanyl-poly(ethylene glycol).

9. The fluorophilic-chemical-encapsulation system of claim 1 wherein the supramolecular structure comprising a number of block-copolymer molecules is a fluorous-core micelle containing block-copolymer molecules each having at least one hydrophilic block, one hydrophobic block, and one fluorinated or semifluorinated block.

10. The fluorophilic-chemical-encapsulation system of claim 1 wherein the supramolecular structure comprising a number of block-copolymer molecules is a hydrophobic-core micelle containing block-copolymer molecules each having at least one hydrophilic block, one fluorinated or semifluorinated block, and one hydrophobic block.

11. The fluorophilic-chemical-encapsulation system of claim 1 wherein the supramolecular structure comprising a number of block-copolymer molecules contains a fluorous-phase region and is one of:

a micelle;

a tube-like supramolecular structure;

a vesicle;

a folded-sheet supramolecular structure;

a bilayer;

a regular film; and

a complex irregular structure.

12. A method for administering a fluorophilic drug, the method comprising:

encapsulating the fluorophilic drug into a supramolecular structure comprising a number of block-copolymer molecules, each block-copolymer molecule containing at least one of

a fluorinated block, and

a semifluorinated block; and

introducing the fluorophilic drug into a patient.

13. The method of claim 12 wherein the fluorophilic drug is introduced into the patient by one of:

injection;

dialysis; and

absorption.

14. The method of claim 12 wherein the fluorophilic drug contains at least one fluorine atom.

15. The method of claim 12 wherein the fluorophilic drug is sevoflurane.

16. The method of claim 12 wherein the supramolecular structure comprising a number of block-copolymer molecules is a fluorous-core micelle comprising one of:

polyethylene-glycol/semifluorinated-alkane block-copolymer molecules; and

polyethylene-glycol/fluorinated-alkane block-copolymer molecules.

17. The method of claim 16 wherein the block-copolymer molecules each includes a polyethylene glycol block containing between 20 and 300 ethoxy monomers.

18. The method of claim 16 wherein the block-copolymer molecules each include one of a semifluorinated alkane and fluorinated alkane having between 4 and 30 carbon atoms.

19. The method of claim 16 wherein the block-copolymer molecules are one of:

2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heneicosafluoro-1-undecanyl-poly(ethylene glycol) mono-methyl ether; and

2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-heptadecafluoro-1-nonanyl-poly(ethylene glycol).

20. The method of claim 12 wherein the supramolecular structure comprising a number of block-copolymer molecules is a fluorous-core micelle containing block-copolymer molecules each having at least one hydrophilic block, one hydrophobic block, and one fluorinated or semifluorinated block.

21. The method of claim 12 wherein the supramolecular structure comprising a number of block-copolymer molecules is a hydrophobic-core micelle containing block-copolymer molecules each having at least one hydrophilic block, one fluorinated or semifluorinated block, and one hydrophobic block.

22. The chemical-encapsulation system of claim 12 wherein the supramolecular structure comprising a number of block-copolymer molecules contains a fluorous-phase region and is one of:

a micelle;

a tube-like supramolecular structure;

a vesicle;

a folded-sheet supramolecular structure;

a bilayer;

a regular film; and

a complex irregular structure.

23. A fluorous-phase-contining micelle component compound comprising:

a polyethylene-glycol block; and

a fluorine-substituted alkane block covalently linked to the polyethylene-glycol block.

24. The fluorous-phase-contining micelle component compound of claim 23 wherein the polyethylene-glycol block includes between 20 and 300 ethoxy monomers.

25. The fluorous-phase-contining micelle component compound of claim 23 wherein the polyethylene-glycol block terminates in a methoxy group.

26. The fluorous-phase-contining micelle component compound of claim 23 wherein the fluorine-substituted alkane block is a semifluorinated alkane having between 4 and 70 carbon atoms.

27. The fluorous-phase-contining micelle component compound of claim 23 wherein the fluorine-substituted alkane block is a fluorinated alkane having between 4 and 30 carbon atoms.

28. The fluorous-phase-contining micelle component compound of claim 23 further comprising one of:

2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heneicosafluoro-1-undecanyl-poly(ethylene glycol) mono-methyl ether; and

2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-heptadecafluoro-1-nonanyl-poly(ethylene glycol).