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Compositions and methods for treating thymic stromal lymphopoietin (tslp)-mediated conditions

A technology of mediation and disease, applied in the direction of biochemical equipment and methods, microorganisms, drug combinations, etc.

Inactive Publication Date: 2011-11-23
REVALESIO CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Conversely, however, mice lacking TSLPR failed to develop asthma in response to inhaled antigens (Zhou et al., supra, and Al-Shami et al., J. Exp. Med., 202:829-839, 2005)

Method used

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  • Compositions and methods for treating thymic stromal lymphopoietin (tslp)-mediated conditions
  • Compositions and methods for treating thymic stromal lymphopoietin (tslp)-mediated conditions
  • Compositions and methods for treating thymic stromal lymphopoietin (tslp)-mediated conditions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0170] (Demonstrating the synergistic effect of the electrokinetic fluid of the present invention and albuterol)

[0171] review. In an art-recognized animal model of human bronchoconstriction (human asthma model), the electrokinetic-altered fluids of the present invention and albuterol provide a synergistic prolongation in vivo (e.g., inhibition of bronchoconstriction), thereby reducing the patient's response to Albuterol use. The results disclosed in this example are also disclosed in the applicant's WO 2009 / 055729.

[0172] First test. In the first experiment, the effect of bronchodilators on airway function in sixteen guinea pigs was assessed in combination with methacholine-induced bronchoconstriction. After determining optimal dosing, each animal was dosed at 50 μg / mL to deliver a target dose of 12.5 μg of albuterol sulfate per animal in 250 μL. The study was a randomized block design for weight and baseline PenH values. Two groups (A and B) received an intratrachea...

Embodiment 2

[0183] (Determining the Effect of the Electrokinetic Altered Fluids of the Invention on Cytokine Expression)

[0184] review. When compared to control fluids, the electrokinetic altered fluids of the present invention reduced pro-inflammatory cytokines (IL-1β, TNF-α, IL-6 and GM-CSF), chemokines (IL-8, MIP- 1α, RANTES and Eotaxin), inflammatory enzymes (iNOS, COX-2 and MMP-9), allergen response (MHC class II, CD23, B7-1 and B7-2) and production of Th2 cytokines (IL-4, IL-13, and IL-5); and increased anti-inflammatory cytokines (eg, IL1R-α, TIMP) compared to control fluids. The results disclosed in this example are also disclosed in the applicant's WO 2009 / 055729.

[0185] In specific aspects, human mixed lymphocytes were stimulated with T3 antigen or PHA in Revalesio oxygen-enriched fluid or control fluid, and IL-1β, IL-2, IL-4, IL-5, IL-6 were assessed , IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-17, eotaxin, IFN-γ, GM-CSF , MIP-1β, MCP-1, G-CSF, FGFb, VEGF, TNF...

Embodiment 3

[0204] (Determining the Effect of the Inventive Electrokinetic Altered Fluids on Modulating T Cell Proliferation)

[0205] review. The electrokinetic-altered fluids of the present invention improved regulatory T cell function as shown by relatively reduced proliferation. The results disclosed in this example are also disclosed in the applicant's WO 2009 / 055729.

[0206] The ability of specific embodiments disclosed herein to modulate T cells was investigated by irradiating antigen presenting cells and introducing antigen and T cells. Typically, these stimulated T cells proliferate. However, normal T cell proliferation was suppressed when regulatory T cells were introduced.

[0207] method. Briefly, FITC-conjugated anti-CD25 (ACT-1 ) antibody used in sorting was purchased from DakoCytomation (Chicago, IL). Other antibodies used were as follows: CD3 (HIT3a in soluble condition), GITR (PE conjugated), CD4 (Cy-5 and FITC conjugated), CD25 (APC conjugated), CD28 (CD28.2 clone ...

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Abstract

Provided are methods for treating a TSLP-mediated or TSLPR-mediated disease or condition, comprising administration of an electrokinetically altered aqueous fluid comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures substantially having an average diameter of less than about 100 nanometers and stably configured in the ionic aqueous fluid in an amount sufficient for treating a TSLP-mediated or TSLPR-mediated disease or condition. The charge-stabilized oxygen-containing nanostructures are preferably stably configured in the fluid in an amount sufficient to provide for modulation of cellular membrane potential and / or conductivity. Certain aspects comprising modulation or down-regulation of TSLP expression and / or activity have utility for treating TSLP-mediated or TSLPR-mediated diseases or conditions as disclosed herein (e.g., disorders of the immune system, allergic inflammation, allergic airway inflammation, DC-mediated inflammatory Th2 responses, atopic dermatitis, atopic eczema, asthma, obstructive airways disease, chronic obstructive pulmonary disease, and food allergies, inflammatory arthritis, rheumatoid arthritis, psoriasis, IgE-mediated disorders, and rhino-conjunctivitis).

Description

field of invention [0001] The present invention relates generally to thymic stromal lymphopoietin (TSLP) and TSLP-mediated disorders, and more particularly, the present invention relates to TSLP and TSLP receptor-mediated disorders (e.g., disorders of the immune system, allergic Inflammation (allergic inflammation), allergic airway inflammation (allergic airway inflammation), DC-mediated inflammatory Th2 response, atopic dermatitis, atopic eczema, allergic asthma (allergic asthma), asthma, obstructive airway disease, chronic obstructive pulmonary disease and food allergies, inflammatory arthritis, rheumatoid arthritis, psoriasis, IgE-mediated disorders and rhinoconjunctivitis). Particularly preferred aspects relate to therapeutic compositions comprising at least one electrokinetically generated fluid as disclosed herein, including gas-enriched (e.g., oxygen-enriched) electrokinetically generated fluids, and in further combination therapy aspects Modulation (eg, treatment) of ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/00C12N5/02
CPCA61K9/0078A61K31/00A61K45/06A61P11/00A61P11/02A61P11/06A61P17/00A61P17/02A61P17/04A61P17/06A61P19/02A61P21/02A61P25/00A61P25/06A61P25/14A61P25/16A61P25/28A61P27/14A61P29/00A61P31/00A61P31/18A61P35/00A61P37/08A61P43/00A61P9/00A61P9/10
Inventor 理查德·L·华森安东尼·B·伍德格雷戈里·J·阿咸宾
Owner REVALESIO CORP
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