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Methods and reagents for the treatment of immunoinflammatory disorders

a technology for immunoinflammatory disorders and reagents, applied in the field of immunoinflammatory disorders, can solve the problems of adverse side effects of their use, and achieve the effects of less toxic, convenient use, and improved efficacy

Inactive Publication Date: 2005-06-02
ZALICUS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0045] The invention also features a method for inhibiting proinflammatory cytokine activity in a patient suffering from or at risk of suffering from a disorder associated with at least one immunoinflammatory disorder mediated by the cytokine by administering to the patient a unit dose of a tetra-substituted pyrimidopyrimidine in an amount effective to inhibit or decrease the cytokine activity in the patient, wherein when the tetra-substituted pyrimidopyrimidine is dipyridamole, the unit dose is suitable for systemic administration. The cytokine is desirably selected from TNFα, IL-1, IL-2, IL-6, IL-12, IL-15, and IFN-γ, and The methods and compositions of the invention desirably have increased effectiveness, safety, tolerability, or satisfaction of treatment of a patient suffering from or at risk of suffering from immunoinflammatory disorder, as compared to methods and compositions using each component of the combination individually.
[0061] By “more effective” is meant that a method, composition, or kit exhibits greater efficacy, is less toxic, safer, more convenient, better tolerated, or less expensive, or provides more treatment satisfaction than another method, composition, or kit with which it is being compared. Efficacy may be measured by a skilled practitioner using any standard method that is appropriate for a given indication.

Problems solved by technology

The effectiveness of these agents can vary and their use is often accompanied by adverse side effects.

Method used

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  • Methods and reagents for the treatment of immunoinflammatory disorders
  • Methods and reagents for the treatment of immunoinflammatory disorders
  • Methods and reagents for the treatment of immunoinflammatory disorders

Examples

Experimental program
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Effect test

example

[0319] The following example is to illustrate the invention, and is not meant to limit the invention in any way.

Methods

[0320] TNFα Secretion Assay

[0321] The effects of test compound combinations on TNFα secretion were assayed in white blood cells from human buffy coat stimulated with LPS or phorbol 12-myristate 13-acetateand ionomycin as follows. Human white blood cells from buffy coat were diluted 1:50 in media (RPMI; Gibco BRL, #11875-085), 10% fetal bovine serum (Gibco BRL, #25140-097), 2% penicillin / streptomycin (Gibco BRL, #15140-122)) and 50 μL of the diluted white blood cells was placed in each well of the assay plate. Drugs were added to the indicated concentration. After 16-18 hours of incubation at 37° C. with 5% CO2 in a humidified incubator, the plate was centrifuged and the supernatant transferred to a white opaque polystyrene 384-well plate (NalgeNunc, Maxisorb) coated with an anti-TNFα antibody (PharMingen, #551220). After a two-hour incubation, the plate was wash...

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Abstract

The invention features a method for treating a patient diagnosed with, or at risk of developing, an immunoinflammatory disorder by administering to the patient a tetra-substituted pyrimidopyrimidine, either alone or in combination with one or more additional agents. The invention also features a composition containing a tetra-substituted pyrimidopyrimidine in combination with one or more additional agents.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims benefit from U.S. Provisional Application No. 60 / 512,415, filed on Oct. 15, 2003, hereby incorporated by reference.BACKGROUND OF THE INVENTION [0002] The invention relates to the treatment of immunoinflammatory disorders. [0003] Immunoinflammatory conditions are characterized by the inappropriate activation of the body's immune defenses. Rather than targeting infectious invaders, the immune response targets and damages the body's own tissues or transplanted tissues. The tissue targeted by the immune system varies with the disorder. For example, in multiple sclerosis, the immune response is directed against the neuronal tissue, while in Crohn's disease the digestive tract is targeted. Immunoinflammatory disorders affect millions of individuals and include conditions such as asthma, allergic intraocular inflammatory diseases, arthritis, atopic dermatitis, atopic eczema, diabetes, hemolytic anaemia, inflammatory der...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K9/20A61K31/415A61K31/519A61K31/525A61K31/5415A61K31/551A61K31/565A61K31/59A61K31/60A61K38/00A61K38/13A61K45/06
CPCA61K9/0073A61K9/209A61K31/519A61K31/565A61K38/13A61K45/06A61K2300/00A61P1/04A61P1/16A61P11/00A61P11/06A61P17/00A61P17/06A61P19/02A61P21/04A61P25/00A61P29/00A61P37/00A61P37/02A61P37/06A61P37/08A61P43/00A61P9/14
Inventor KEITH, CURTISBORISY, ALEXISZIMMERMANN, GRANT R.JOST-PRICE, EDWARD ROYDONMANIVASAKAM, PALANIYANDIHURST, NICOLEFOLEY, MICHAEL A.SLAVONIC, MICHAEL S.SMITH, BRENDANAUSPITZ, BENJAMIN A.
Owner ZALICUS INC
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