Methods for ameliorating and preventing central nervous system inflammation

Patent metadata

Field	Value
Publication number	US-9944583-B2
Application number	US-201615136787-A
Country	US
Kind code	B2
Filing date	Apr 22, 2016
Priority date	Oct 19, 2007
Publication date	Apr 17, 2018
Grant date	Apr 17, 2018

Abstract

The invention provides compositions and methods for ameliorating, treating, reversing or preventing pathology or inflammation in the central nervous system (CNS), or the brain, caused or mediated by NFkB, IL-6, IL-6-R, NADPH oxidase (Nox), and/or superoxide and/or hydrogen peroxide production by a NADPH oxidase, including for example ameliorating, treating, reversing or preventing schizophrenia, psychosis, delirium, e.g., post-operative delirium, drug-induced psychosis, psychotic features associated with frailty syndrome (FS), aging, depression, dementias; traumatic war neurosis, post traumatic stress disorder (PTSD) or post-traumatic stress syndrome (PTSS), Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's Disease), and/or Multiple Sclerosis (MS). The invention also provides methods for purifying a C60 fullerene, C 3 (tris malonic acid C60) or malonic acid derivatives.

First claim

What is claimed is:

1. A method for purifying a C60 malonic acid (propanedioic acid) derivative, the method comprising:
(a) dissolving an impure powder form of a C60 malonic acid derivative in a dilute sodium hydroxide (NaOH) solution at a concentration of between about 1 mM to 400 mM at about 4 degrees C. with stirring;
(b) adding a second solution of NaOH more concentrated than the dilute NaOH solution in step (a) drop-wise to the solution of step (a) to achieve an approximately neutral pH;
(c) incubating the solution of step (b) at 4 degrees C. in the dark for approximately 0.5 to 3 hours;
(d) centrifuging the solution after the incubating of step (c) to produce a clear dark red supernatant and a solid light pink pellet;
(e) removing the supernatant to a different container;
(f) incubating the supernatant removed in step (e) at 4 degrees C. for an additional about 3 to 4 hours; and
(g)
(1) re-centrifuging to remove substantially all or all undissolved material to generate a pellet and a solution comprising purified C 3 , wherein the pellet comprises an insoluble waxy material containing contaminant and small amounts of residual C 3 , or
(2) filtering the sample through a filter which allows only aqueous solutions to pass, thereby removing an insoluble waxy contaminant after solubilization in dilute NaOH, thereby generating a solution comprising purified C 3 .

2. A method for purifying a C60 malonic acid (propanedioic acid) derivative, the method comprising:
(a) providing a solution comprising an impure powder form of a C60 malonic acid derivative;
(b) providing an antibody directed against a C60 fullerene or a C60 malonic acid derivative;
and
(c) isolating the C60 fullerene or the C60 malonic acid derivative by incubating the antibody with the C60 fullerene or the C60 malonic acid derivative under conditions wherein the antibody specifically binds to the C60 fullerene, or the C60 malonic acid derivative.

3. The method of claim 1 , wherein the purified C 3 solution is further treated to remove a minor amount of volatile contaminant by vaccum distillation or by bubbling an inert gas through the solution.

4. The method of claim 1 , wherein the C60 malonic acid derivative comprises a C 3 (tris malonic acid C60 macrocyclic malonate derivative.

5. The method of claim 4 , wherein the malonate is fuctionalized with a halide atom.

6. The method of claim 4 , wherein a malonate ester group is replaced by an alkyne group,
and optionally the alkyne group comprises a dialkynylmethanofullerene.

7. The method of claim 2 , wherein an antibody-C60 fullerene complex or an anitbody-C 3 (tris malonic acid C60) or antibody-malonic acid derivative complex is purified by gel electrophoresis purification, HPLC, immunoprecipitation, column chromatography, differential centrifugation or affinity column chromatography.

8. The method of claim 2 , wherein the C60 malonic acid derivative is or comprises a C 3 (tris molanic acid C60 fullerene) or a C60 macrocyclic malonate derivative.

9. The method of claim 8 , wherein the malonate is functionalized with a halide atom.

10. The method of claim 8 , wherein a malonate ester group is replaced by an alkyne group,
and optionally the alkyne group comprises a dialkynylmethanofullerene,
and optionally the malonate is functionalized with halide atom, or malonate ester groups are replaced by alkyne groups, optionally as a dialkynylmethanofullerene.

11. The method of claim 2 , wherein, the C60 malonic acid derivative is a C 3 (tris malonic acid C60 fullerene).

Assignees

• Univ California

Inventors

• Dugan Laura L
• Behrens Marie Margarita
• Ali Sameh

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07C2604/00

  Fullerenes, e.g. C60 buckminsterfullerene or C70 · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07C51/47 Primary

  by solid-liquid treatment; by chemisorption · CPC title

• A61K31/194

  having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid · CPC title