Higher fullerenes useful as radical scavengers

• US 7,825,161 B2
• Filed: 12/15/2004
• Issued: 11/02/2010
• Est. Priority Date: 12/15/2003
• Status: Active Grant

• Current Assignee: Nano-C, Inc.
• Original Assignee: Nano-C, Inc.
• Inventors: Hummelen, Jan C., Sieval, Alexander B., Kronholm, David F.
• Primary Examiner(s): Puttlitz; Karl J
• Application Number:
  US11/014,207
• Publication Number:
  US 20050239717A1
• Time in Patent Office: 2,148 Days
• Field of Search: None
• US Class Current: 514/577
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07C 2604/00 Fullerenes, e.g. C60 buckminsterfullerene or C70
• CPC Class Codes: C07C 69/00 Esters of carboxylic acids; Esters of carbonic or haloformic acids ortho esters, see the relevant groups, e.g. C07C43/32
• CPC Class Codes: C07C 69/616 polycyclic

Abstract

Chemically functionalized fullerenes are useful in various applications as radical scavengers. These chemically functionalized fullerenes offer the advantages of preservation of the high innate radical scavenging efficiency of the fullerene cage and ease of synthesis of fullerene derivatives of desirably altered chemical and physical properties and single isomers. Further, they are based on a common intermediate chemistry and intermediates can be easily functionalized and tailored to various requirements.

Claims

1. A method of scavenging free radicals, the method comprising:

administering one or more free radical scavenging compounds to a dermal substrate, and

reducing the levels of free radicals without significantly increasing pro-oxidant activity while the one or more free radical scavenging compounds is on the dermal substrate and is exposed to irradiation,

wherein the one or more free radical scavenging compounds are selected from the group consisting of C₈₄ fullerene and C₈₄(Y)_m, where C₈₄ is a fullerene, Y is a moiety attached, directly or indirectly, to the C₈₄ fullerene, where m is in the range of 1 to 30, and Y is selected from the group consisting of lipophilic moieties, hydrophilic moieties, amphiphilic moieties, free radical scavenging moieties, or bio-site specific moieties.

2. The method of claim 1, wherein the one or more free radical scavenging compounds do not significantly increase pro-oxidant activity due to triplet excited states of the one or more free radical scavenging compounds.

3. The method of claim 1, wherein the one or more free radical scavenging compounds do not generate singlet oxygen.

4. The method of claim 1, wherein Y comprises a lipophilic moiety and the lipophilic moiety is selected from the group consisting of alkanes, fatty acid, fatty esteramine, fatty alcohols, and fatty amine moieties.

5. The method of claim 1, wherein Y comprises a lipophilic moiety and the compound is capable of transport through or solubilization in lipid phases in a biological system.

6. The method of claim 1, wherein Y comprises a hydrophilic moiety.

7. The method of claim 6, wherein the hydrophilic moiety is selected from the group consisting of poly-(ethylene oxide)s, mono-, di- or poly-hydroxylated alkanes, mono-, di- or poly-hydroxylated cycloalkanes, amino alkanes, diamino alkanes, mono-, di-, or poly-saccharides, hydroxides, ammonium groups, alkylated ammonium groups, phosphates, alkylphosphates, sulfonates, and alkylsulfonates, phosphonium groups, carboxylate groups, sulfonic acid groups, iminium groups, imidine groups, and imidinium groups.

8. The method of claim 6, wherein Y comprises a hydrophilic moiety and the compound is capable of transport through or solubilization in aqueous phases in a biological system.

9. The method of claim 1, wherein Y comprises a chemical moiety that is independently effective as a free radical scavenger.

10. The method of claim 1, wherein Y comprises an amphiphilic moiety.

11. The method of claim 10, wherein the amphiphilic moiety is selected from the group consisting of polyethylene glycol, poly(ethylene oxide)s, propylene glycol, polypropylene glycol), hexylene glycol, diethylene glycol, propylene glycol n-alkanols, and glycol moieties.

12. The method of claim 1, wherein Y comprises a moiety which addresses a biological target such as [monoclonal] antibodies, proteins, enzymes, protein hormones, membrane proteins, steroids, coenzymes, co-factors, [oligo] DNA, RNA, enzyme inhibitors, enzyme substrates, specific cells or organs, tissues.

25. The method of claim 1 or 13, further comprising:

exposing the target to at least one additional radical scavenging compound.

26. The method of claim 1 or 13, wherein the compound further comprises:

an additive selected to enhance or preserve the efficacy of the compound.

13. A method of scavenging free radicals, comprising:

administering to a dermal substrate a compound having the formula,

14. The method of claim 13, wherein the compound does not significantly increase pro-oxidant activity due to triplet excited states of the compound.

15. The method of claim 13, wherein the lipophilic moiety is selected from the group consisting of alkanes, fatty acid, fatty esteramine, fatty alcohol, and fatty amine moieties.

16. The method of claim 15, wherein one or more of X and Z comprises a lipophilic moiety and the compound is capable of transport through or solubilization in lipid phases in a biological system.

17. The method of claim 13, wherein X or Z comprises a hydrophilic moiety.

18. The method of claim 16, wherein the hydrophilic moiety is selected from the group consisting of poly-(ethylene oxide)s, mono-, di- or poly-hydroxylated alkanes, mono-, di- or poly-hydroxylated cycloalkanes, amino alkanes, diamino alkanes, mono-, di-, or poly-saccharides, hydroxides, ammonium groups, alkylated ammonium groups, phosphates, alkylphosphates, sulfonates, and alkylsulfonates, phosphonium groups, carboxylate groups, sulfonic acid groups, iminium groups, imidine groups, and imidinium groups.

19. The method of claim 17, wherein one or more of X and Z comprises a hydrophilic moiety and the compound is capable of transport through or solubilization in aqueous phases in a biological system.

20. The method of claim 13, one or more of X and Z comprises a chemical moiety that is independently effective as a free radical scavenger.

21. The method of claim 13, wherein one or more of X and Z comprises an amphiphilic moiety.

22. The method of claim 21, wherein the amphiphilic compound is selected from the group consisting of polyethylene glycol, poly(ethylene oxide)s, propylene glycol, polypropylene glycol), hexylene glycol, diethylene glycol, propylene glycol n-alkanols, and glycol moieties.

23. The method of claim 13, wherein one or more of X and Z is a non-electron withdrawing group.

24. The method of claim 23, wherein the non-electron withdrawing group is selected from the group consisting of alkyls, cyclic alkyls, substituted alkyls, alkylaryls, alkyl ethers, alkylaryl ethers, alkyl thioethers, alkylaryl thioethers, alkyl esters, alkylaryl esters, alkyl thioesters, alkylaryl thioesters, alkyl amides, alkylaryl amides, alkyl amines, alkylaryl amines, alkyl anhydrides, alkylaryl anhydrides, alkyl carbonates (or carboxylic acids), alkylaryl carbonates, arylalkyls, aryl ethers, arylalkyl ethers, aryl thioethers, arylalkyl thioethers, aryl esters, arylalkyl esters, aryl thioesters, arylalkyl thioesters, aryl amides, arylalkyl amides, aryl amines, arylalkyl amines, aryl anhydrides, arylalkyl anhydrides, aryl carbonates (or carboxylic acids) and arylalkyl carbonates.