FULLERENE THERAPIES FOR INFLAMMATION AND INHIBITION OF BUILD-UP OF ARTERIAL PLAQUE
Described herein are methods for treating inflammatory disorders or for inhibiting the build-up of arterial plaque. The methods comprise administering to a subject in need thereof a therapeutically effective amount of a synthetically modified fullerene.
1 . A method for treating an inflammatory disease, comprising administering to a subject in need thereof a therapeutically effective amount of a synthetically modified fullerene of the formula
Z m —F—Y n
wherein F is a fullerene of formula C p or X@C p , the fullerene having two opposing poles and an equatorial region;
C p represents a fullerene cage having p carbon atoms, and X@C p represents such a fullerene cage having a chemical group X within the cage;
Z and Y are positioned near respective opposite poles of C p ;
m is an integer of from 1 to 5 and Z is a hydrophilic, lipophilic, or amphiphilic moiety;
n is an integer of from 1 to 5 and Y is a hydrophilic moiety;
p is an even number between 60 and 200; and
X, if present, represents one or more metal atoms within the fullerene (F), optionally in the form of a trinitride of formula G i=1-3 H k=3-i N in which G and H are metal atoms.
2 . The method of claim 1 , wherein p is an even number between 60 and 96.
3 . The method of claim 2 , wherein p is 60 or 70.
4 . The method of claim 1 , wherein said synthetically modified fullerene is a prolate ellipsoid shaped fullerene having a major axis such that said poles are located at opposing ends of the major axis of the prolate ellipsoid fullerene.
5 . The method of claim 1 , wherein said synthetically modified fullerene is spheroid with opposing poles defined by an axis through opposing carbon rings.
6 . A method for treating an inflammatory disease, comprising administering to a subject in need thereof a therapeutically effective amount of a synthetically modified fullerene of the formula
Z(C p )Y
wherein p is an even number between 60 and 200; Y is a hydrophilic moiety covalently connected to C p , optionally through a linking group, at or near a pole thereof; and Z is a hydrophilic, lipophilic, or amphiphilic moiety covalently connected to C p , optionally through a linking group, at or near a pole opposite to said Y.
7 . The method of claim 6 , wherein C p is C 70 .
8 . The method of claim 6 , wherein Z comprises at least one —(CH 2 ) q CH 3 or —(OCH 2 CH 2 ) w OCH 3 moiety, wherein q is an integer of from 5 to 17 and w is an integer of from 1 to 6.
9 . The method of claim 6 , wherein: (a) Z comprises at least one niacin moiety at a free end thereof; (b) Z comprises at least one —C(O)O— moiety; (c) Y comprises at least one niacin moiety at a free end thereof; or (d) Y comprises at least one —C(O)O— moiety.
10 . The method of claim 6 , wherein: (a) Z comprises two niacin moieties at two free ends thereof; (b) Z comprises two —C(O)O— moieties; (c) Y comprises two niacin moieties at two free ends thereof; or (d) Y comprises at least two —C(O)O— moieties.
11 . The method of claim 6 , wherein the synthetically modified fullerene is selected from the group consisting of
12 . The method of claim 6 , wherein the inflammatory disease is inflammatory arthritis or an allergic disease.
13 . A method of inhibiting build-up of arterial plaque, comprising administering a therapeutically effective amount of one or more fullerenes to a subject in need thereof.
14 . The method of claim 13 , wherein said fullerenes inhibit accumulation of LDL in foam cells of the subject.
15 . The method of claim 13 , wherein said fullerenes are delivered directly to the foam cells of the subject.
16 . The method of claim 13 , wherein said subject is a human.
17 . The method of claim 13 , wherein at least one of said one or more fullerenes is a synthetically modified fullerene of the formula
Z m —F—Y n
wherein F is a fullerene of formula C p or X@C p , the fullerene having two opposing poles and an equatorial region;
C p represents a fullerene cage having p carbon atoms, and X@C p represents such a fullerene cage having a chemical group X within the cage;
Z and Y are positioned near respective opposite poles of C p ;
m is an integer of from 1 to 5 and Z is a hydrophilic, lipophilic, or amphiphilic moiety;
n is an integer of from 1 to 5 and Y is a hydrophilic moiety;
p is an even number between 60 and 200; and
X, if present, represents one or more metal atoms within the fullerene (F), optionally in the form of a trinitride of formula G i=1-3 H k=3-i N in which G and H are metal atoms.
18 . The method of claim 17 , wherein p is 60 or 70.
19 . The method of claim 17 , wherein at least one of said one or more fullerenes is a synthetically modified fullerene of the formula
Z(C p )Y
wherein p is an even number between 60 and 200; Y is a hydrophilic moiety covalently connected to C p , optionally through a linking group, at or near a pole thereof, and wherein Z is a hydrophilic, lipophilic, or amphiphilic moiety covalently connected to C p , optionally through a linking group, at or near a pole opposite to said Y.
20 . The method of claim 19 , wherein C p is C 70 .
21 . The method of claim 19 , wherein Z comprises at least one —(CH 2 ) q CH 3 or —(OCH 2 CH 2 ) w OCH 3 moiety, wherein q is an integer of from 5 to 17 and w is an integer of from 1 to 6.
22 . The method of claim 19 , wherein: (a) Z comprises at least one niacin moiety at a free end thereof; (b) Z comprises at least one —C(O)O— moiety; (c) Y comprises at least one niacin moiety at a free end thereof; or (d) Y comprises at least one —C(O)O— moiety.
23 . The method of claim 19 , wherein: (a) Z comprises two niacin moieties at two free ends thereof; (b) Z comprises two —C(O)O— moieties; (c) Y comprises two niacin moieties at two free ends thereof; or (d) Y comprises at least two —C(O)O— moieties.
24 . The method of claim 19 , wherein the synthetically modified fullerene is selected from the group consisting of
25 . A synthetically modified fullerene of the formula
Z m —F—Y n
wherein F is a fullerene of formula C p or X@C p , the fullerene having two opposing poles and an equatorial region;
C p represents a fullerene cage having p carbon atoms, and X@C p represents such a fullerene cage having a chemical group X within the cage.
Z and Y are positioned near respective opposite poles of C p ;
m is an integer of from 1 to 5 and Z is a hydrophilic, lipophilic, or amphiphilic moiety;
n is an integer of from 1 to 5 and Y is a hydrophilic moiety;
p is an even number between 60 and 200; and
X, if present, represents one or more metal atoms within the fullerene (F), optionally in the form of a trinitride of formula G i=1-3 H k=3-i N in which G and H are metal atoms,
wherein: (a) Z comprises at least one niacin moiety at a free end thereof; (b) Z comprises at least one —C(O)O— moiety; (c) Y comprises at least one niacin moiety at a free end thereof; or (d) Y comprises at least one —C(O)O— moiety.
26 . The method of claim 25 , wherein: (a) Z comprises two niacin moieties at two free ends thereof; (b) Z comprises two —C(O)O— moieties; (c) Y comprises two niacin moieties at two free ends thereof; or (d) Y comprises at least two —C(O)O— moieties.
27 . A compound selected from the group consisting of is selected from the group consisting of