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Treatment of macrophage-related disorders

a macrophage and disorder technology, applied in the field of treatment of macrophage-related disorders, can solve the problems of inflammation that can dismantle tissues to the point of inflicting serious injury

Inactive Publication Date: 2012-05-31
RGT UNIV OF CALIFORNIA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0020]In some embodiments, modulating of macrophage activation or accumulation according to the invention comprises modulating one or more molecules involved in one or more cellular pathways selected from the group consisting of NFkB, toll-like receptor (TLR)-2, TLR-4, Tie-2/Ang-2, TRIF/TBK1/IRF3, NFAT, and hypoxia-induced pathways, lipopolysaccharide (LPS), prostaglandin E2 (PGE2), interferon (IFN)-α, IFN-β, IFN-γ, interleukin (IL)-1, IL-4, IL-6, sIL1Ra, IL-8, IL-10, IL-12, IL-12p40, IL-13, IP10, MHCII, TNF-α, macrophage inflammatory protein 1 alpha (MIP1-α), IFN-gamma-inducing factor (IGIF), macrophage-stimulating protein (MSP), inter-cellular adhesion molecule 1(ICAM-1), colony

Problems solved by technology

These actions can result in inflammation that can dismantle tissues to the point of inflicting serious injury.

Method used

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  • Treatment of macrophage-related disorders
  • Treatment of macrophage-related disorders
  • Treatment of macrophage-related disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

Purification of Chlorite

[0513]This procedure was performed in diminished light, e.g., with overhead lights off, and out of direct sunlight.

[0514]Sodium Chlorite (80 wt %, Sigma-Aldrich lot #09911CD) was dissolved in 1000 mL of distilled water. The flask was mounted to a rotary evaporator, and the bath temperature set to 70° C. Vacuum was applied, and increased until the water began to distill over in a controlled manner. The vacuum was applied until the mixture put down a load of solids, and 550 mL of water had distilled over. Using a coarse sintered glass funnel, the solids were removed by suction filtration of the hot solution. These solids were mostly sodium chloride.

[0515]The filtrate was stored at −25° C. for a period of time sufficient to precipitate the chlorite (approximately 24 hours). The entire mixture froze solid. The frozen mixture was broken up and centrifugally filtered while cold. Purified sodium chlorite was collected as the frozen solid melted. The centrifuge had a...

example 2

Purification of Chlorite

[0516]The method described in Example 1 was performed, but using coarse sintered glass suction filtration rather than centrifugal filtration for the cold filtration. After the first filtration, chlorite purity after the first crystallization was 91.9%. The crystallization step was repeated a second time. After the second recrystallization / suction filtration, the chlorite was 99.5% pure.

[0517]In one method, a suspension of NaClO2 (technical grade, 80% purity) is triturated with water at 17-25° C., the suspension is stored at −25° C. to −5° C., and the cold mixture is filtered. The series of steps is repeated until the sodium chlorite assay shows ≧99.0% area under the curve the ion chromatography.

[0518]FIG. 5 shows a Thermo-Gravimetric Analysis (TGA) of a sample of sodium chlorite purified according to the invention. The thermogram shows the loss of a total of 40.0% weight from ambient temperature to about 160° C. FIG. 6 shows an X-ray powder diffraction (XRPD)...

example 3

Adjustment of Chlorite Formulation pH

[0519]To prepare a chlorite formulation at a lower pH, sodium chlorite purified by the method of Example 2 was dissolved in distilled water and stirred using a magnetic stirrer. A calibrated pH probe was put in the solution. Small amounts of monosodium phosphate monohydrate were added, until the pH reached and stabilized at 7.62. In the event of the pH drifting lower than the target pH, the pH can be adjusted back with 0.1 N NaOH.

[0520]This solution was sampled, and assayed for sodium chlorite content by HPLC. Column: Novosep A-2 Alltech 250×4 mm; eluant: 3.6 mM sodium carbonate. Rate: 0.8 mL / min. Detected with a suppressed Alltech 650 conductivity detector. Quantitation was performed by standard iodimetry. See Inorganic Syntheses, section under Chlorine (IV) Oxide; Sodium Chlorite analysis, p. 156. The concentration was determined to be 1.36 M. To prepare a 4.25 wt % solution (0.47 M), 200 mL were diluted to 580 mL.

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Abstract

The present invention provides a method of treating a macrophage related disease comprising administering to a subject in need thereof an effective amount of an oxidative agent or an immunosuppressive agent. The present invention also provides a method of modulating macrophage accumulation or activation comprising administering to a subject in need thereof an effective amount of an oxidative agent or an immunosuppressive agent. The oxidative agent can be chlorite or a chlorite containing compound.

Description

[0001]This application claims benefit under 35 U.S.C. §119(e) to Provisional Application Nos. U.S. 61 / 231,989, filed Aug. 6, 2009, U.S. 61 / 232,678, filed Aug. 10, 2009, and U.S. 61 / 238,609, filed Aug. 31, 2009, each of which is herein incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Macrophages are white blood cells produced by the division of monocytes. Monocytes and macrophages are phagocytes, and play a role in innate immunity (non-specific immune defenses) as well as helping to initiate adaptive immunity (specific defense mechanisms). These cells phagocytose (engulf and then digest) cellular debris and pathogens either as stationary or as mobile cells. When activated by pathogens or by other mechanisms, macrophages stimulate and recruit lymphocytes and other immune cells to respond to the insult.[0003]Although macrophages play a vital role in host immune defenses, activated macrophages are also involved in the progression of a number of diseases and dis...

Claims

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Application Information

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IPC IPC(8): A61K33/00A61K31/18G01N33/53A61P3/10A61P25/28A61P25/16A61K31/4166A61K49/00A61K33/243
CPCA61K31/10C07K16/2839A61K31/327A61K33/00A61K33/04A61K33/16A61K33/18A61K33/20A61K33/24A61K33/32A61K33/38A61K33/40A61K45/06G01N2333/70596A61K31/185A61K39/3955A61K31/7076A61K31/137A61K2300/00A61P1/02A61P11/00A61P11/06A61P21/00A61P25/00A61P25/16A61P25/28A61P29/00A61P3/04A61P31/00A61P33/02A61P35/00A61P37/06A61P43/00A61P7/00A61P9/10A61P9/12A61P3/10Y02A50/30A61K33/243
Inventor MCGRATH, MICHAEL S.AZHIR, ARASTEH ARI
Owner RGT UNIV OF CALIFORNIA
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