Fullerene compositions for ameliorating hearing loss, collateral damage of chemotherapy, or mucositis

• US 20060047003A1
• Filed: 08/29/2005
• Published: 03/02/2006
• Est. Priority Date: 09/02/2004
• Status: Abandoned Application

• Current Assignee: Luna Innovations, Inc.
• Original Assignee: Luna Innovations, Inc.
• Inventors: Lebovitz, Russ
• Application Number:
  US11/214,469
• Publication Number:
  US 20060047003A1
• Time in Patent Office: Days
• US Class Current: 514/569
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: C01B 32/15 Nano-sized carbon materials
• CPC Class Codes: C01B 32/156 After-treatment

Abstract

This patent discloses a method of ameliorating a hearing loss, collateral damage of chemotherapy, or mucositis in a mammal, comprising administering a composition comprising a substituted fullerene to the mammal afflicted with the hearing loss, collateral damage of chemotherapy, or mucositis or potentially afflicted with the hearing loss, collateral damage of chemotherapy, or mucositis wherein the substituted fullerene comprises a fullerene core (Cn) and at least one of: (i) from 1 to 3 (>CX¹X²) groups bonded to the fullerene core; (ii) from 1 to 18 —X³ groups bonded to the fullerene core; (iii) from 1 to 6 —X⁴-groups bonded to the fullerene core; or (iv) from 1 to 6 dendrons bonded to the fullerene core.

Claims

1. A method of ameliorating a hearing loss, collateral damage of chemotherapy, or mucositis in a mammal, comprising:

administering a composition comprising a substituted fullerene to the mammal afflicted with the hearing loss, collateral damage of chemotherapy, or mucositis or potentially afflicted with the hearing loss, collateral damage of chemotherapy, or mucositis, wherein the substituted fullerene comprises a fullerene core (Cn) and at least one of;

(i) from 1 to 3 (>

CX¹X²) groups bonded to the fullerene core;

(ii) from 1 to 18 —

X³ groups bonded to the fullerene core;

(iii) from 1 to 6 —

X⁴ groups bonded to the fullerene core;

or

(iv) from 1 to 6 dendrons bonded to the fullerene core.

2. The method of claim 1, wherein the substituted fullerene comprises a fullerene core (Cn) having 60 carbon atoms or 70 carbon atoms.

3. The method of claim 1, wherein each X¹ and X² is independently selected from —

H, —

COOH, —

CONH₂, —

CONHR′

, —

CONR′

₂, —

COOR′

, —

CHO, —

(CH₂)_dOH, —

R, —

RCOOH, —

RCONH₂, —

RCONHR′

, —

RCONR′

₂, —

RCOOR′

, —

RCHO, —

R(CH₂)_dOH, or a salt thereof, wherein each R is a hydrocarbon moiety having from 1 to about 6 carbon atoms and each R′

is independently (i) a hydrocarbon moiety having from 1 to about 6 carbon atoms, (ii) an aryl-containing moiety having from 6 to about 18 carbon atoms, (iii) a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or (iv) an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol, and d is an integer from 0 to about 20.

4. The method of claim 1, wherein the substituted fullerene comprises C₆₀ and 3 (>

CX¹X²) groups in the C3 orientation or the D3 orientation.

5. The method of claim 1, wherein the substituted fullerene comprises C₆₀ and 2 (>

CX¹X²) groups in the trans-2 orientation, the trans-3 orientation, the e orientation, or the cis-2 orientation.

6. The method of claim 1, wherein the substituted fullerene comprises C₇₀ and 2 (>

CX¹X²) groups in the bis orientation.

7. The method of claim 1, wherein the substituted fullerene has the structure shown in FIG. 7B.

8. The method of claim 1, wherein the substituted fullerene comprises from I to about 6 —

X³ groups and each —

X³ group is independently selected from;

—

N⁺(R²)(R³)(R⁴), wherein R², R³, and R⁴ are independently —

H or —

(CH₂)_d—

CH₃, wherein d is an integer from 0 to about 20;

—

N(R²)(R³)(R⁸), wherein R² and R³ are independently —

H or —

(CH₂)_d—

CH₃, wherein d is an integer from 0 to about 20, and each R⁸ is independently —

(CH₂)_f—

SO₃⁻

, —

(CH₂)_f—

PO₄⁻

, or —

(CH₂)_f—

COO⁻

, wherein f is an integer from 1 to about 20;

—

C(R⁵)(R⁶)(R⁷), wherein R⁵, R⁶, and R⁷ are independently —

COOH, —

H, —

CH(═

O), or —

CH₂OH;

—

C(R²)(R³)(R⁸), wherein R² and R³ are independently —

H or —

(CH₂)_d—

CH₃, wherein d is an integer from 0 to about 20, and each R⁸ is independently —

(CH₂)_f—

SO₃⁻

, —

(CH₂)_f—

PO₄⁻

, or —

(CH₂)_f—

COO²⁰, wherein f is an integer from 1 to about 20;

—

(CH₂)_e—

COOH, —

(CH₂)_e—

CONH₂, —

(CH₂)_e—

COOR′

, or a peptidyl moiety, wherein e is an integer from 1 to about 6 and each R′

is independently (i) a hydrocarbon moiety having from 1 to about 6 carbon atoms, (ii) an aryl-containing moiety having from 6 to about 18 carbon atoms, (iii) a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or (iv) an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol;

or

an aromatic heterocyclic moiety containing a cationic nitrogen.

9. The method of claim 1, wherein each —

X⁴—

group is independently

10. The method of claim 1, wherein each —

X⁴—

group is independently

11. The method of claim 1, wherein each —

X⁴—

group is independently

12. The method of claim 1, wherein the substituted fullerene has a structure selected from FIGS. 8A-8G.

13. The method of claim 1, wherein the substituted fullerene comprises an endohedral metal.

14. The method of claim 1, wherein the composition further comprises an amphiphilic fullerene having the formula (B)_b-C_n-(A)_a, wherein C_n is a fullerene moiety comprising n carbon atoms, wherein n is an integer and 60≦

n≦

240;

B is an organic moiety comprising from 1 to about 40 polar headgroup moieties;

b is an integer and 1≦

b≦

5;

each B is covalently bonded to the C_n through 1 or 2 carbon-carbon, carbon-oxygen, or carbon-nitrogen bonds;

A is an organic moiety comprising a terminus proximal to the C_n and one or more termini distal to the C_n, wherein the termini distal to the C_n each comprise —

C_xH_y, wherein x is an integer and 8≦

x≦

24, and y is an integer and 1≦

y≦

2x+1;

a is an integer, 1≦

a≦

5;

2≦

b+a≦

6; and

each A is covalently bonded to the C_n through 1 or 2 carbon-carbon, carbon-oxygen, or carbon-nitrogen bonds.

15. A composition for ameliorating a hearing loss, collateral damage of chemotherapy, or mucositis in a mammal, comprising:

a substituted fullerene; and

a carrier

wherein the substituted fullerene comprises a fullerene core (Cn) and at least one of;

(i) from 1 to 3 (>

CX¹X²) groups bonded to the fullerene core;

(ii) from 1 to 18 —

X³ groups bonded to the fullerene core;

(iii) from 1 to 6 —

X⁴—

groups bonded to the fullerene core;

or

(iv) from 1 to 6 dendrons bonded to the fullerene core.

16. The composition of claim 15, wherein each X¹ and X² is independently selected from —

H, —

COOH, —

CONH₂, —

CONHR′

, —

CONR′

₂, —

COOR′

, —

CHO, —

(CH₂)_dOH, —

R, —

RCOOH, —

RCONH₂, —

RCONHR′

, —

RCONR′

₂, —

RCOOR′

, —

RCHO, —

R(CH₂)_dOH, or a salt thereof, wherein each R is a hydrocarbon moiety having from 1 to about 6 carbon atoms and each R′

is independently (i) a hydrocarbon moiety having from 1 to about 6 carbon atoms, (ii) an aryl-containing moiety having from 6 to about 18 carbon atoms, (iii) hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or (iv) an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol, and d is an integer from 0 to about 20.

17. The composition of claim 15, wherein the substituted fullerene has the structure shown in FIG. 7B.

18. The composition of claim 15, wherein the substituted fullerene comprises from 1 to about 6 —

X³ groups and each —

X³ group is independently selected from;

—

N⁺(R²)(R³)(R⁴), wherein R², R³, and R⁴ are independently —

H or —

(CH₂)_d—

CH₃, wherein d is an integer from 0 to about 20;

—

N(R²)(R³)(R⁸), wherein R² and R³ are independently —

H or —

(CH₂)_d—

CH₃, wherein d is an integer from 0 to about 20, and each R⁸ is independently —

(CH₂)_f—

SO₃⁻

, —

(CH₂)_f—

PO₄⁻

, or —

(CH₂)_f—

COO⁻

, wherein f is an integer from 1 to about 20;

—

C(R⁵)(R⁶)(R⁷), wherein R⁵, R⁶, and R⁷ are independently —

COOH, —

H, —

CH(═

O), or —

CH₂OH;

—

C(R²)(R³)(R⁸), wherein R² and R³ are independently —

H or —

(CH₂)_d—

CH₃, wherein d is an integer from 0 to about 20, and each R⁸ is independently —

(CH₂)_f—

SO₃⁻

, —

(CH₂)_f—

PO₄⁻

, or —

(CH₂)_f—

COO⁻

, wherein f is an integer from 1 to about 20;

—

(CH₂)_e—

COOH, —

(CH₂)_e—

CONH₂, —

(CH₂)_e—

COOR′

, or a peptidyl moiety, wherein e is an integer from 1 to about 6 and each R′

is independently (i) a hydrocarbon moiety having from 1 to about 6 carbon atoms, (ii) an aryl-containing moiety having from 6 to about 18 carbon atoms, (iii) a hydrocarbon moiety having from 1 to about 6 carbon atoms and a terminal carboxylic acid or alcohol, or (iv) an aryl-containing moiety having from 6 to about 18 carbon atoms and a terminal carboxylic acid or alcohol;

or

an aromatic heterocyclic moiety containing a cationic nitrogen.

19. The composition of claim 15, wherein each —

X⁴—

group is independently

20. The composition of claim 15, wherein each —

X⁴—

group is independently

21. The composition of claim 15, wherein each —

X⁴—

group is independently

22. The composition of claim 15, wherein the substituted fullerene has a structure selected from FIGS. 8A-8G.