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Oral composition comprising a TNF antagonist and use thereof

a technology of oral composition and tnf receptor, which is applied in the direction of antibody mimetics/scaffolds, receptors for cytokines/lymphoines/interferons, animals/human proteins, etc., can solve the problem of no oral tnf antagonist or anti-tnf alpha receptor in the market, and achieve the effect of reducing or preventing the effect, constant weight, and weight loss

Inactive Publication Date: 2014-09-11
HADASIT MEDICAL RES SERVICES & DEVMENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method of treating or reducing the effects of medicines that can damage the liver, such as acetaminophen (also known as paracetamol). This is done by giving the person a substance called a TNF antagonist. The technical effect is that this method can protect the liver from damage caused by these medicines.

Problems solved by technology

Currently, there is no oral TNF antagonist or anti TNF alpha receptor in the market due to the high acidity and enzymatic degradation in the stomach that inactivates or destroys the molecule before reaching the blood circulation.

Method used

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  • Oral composition comprising a TNF antagonist and use thereof
  • Oral composition comprising a TNF antagonist and use thereof
  • Oral composition comprising a TNF antagonist and use thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0086]Measurement of the effect of ENBREL® (ETANERCEPT) on weight loss

Methods:

[0087]Medicine preparation: One ampoule of ETANERCEPT containing 25 mg was dissolved with 1 ml of vehicle (=25 mg / ml, 2500 μg / 1000 μl) according to the manufacturer's instructions.

[0088]Animals: Male C57BL / 6 (B6) mice (12-13 weeks old) were purchased from Harlan Laboratories (Jerusalem, Israel). All mice were maintained in specific pathogen-free conditions. Mice were maintained in the Animal Core of the Hadassah-Hebrew University Medical School. All mice were administered standard laboratory chow and water ad libitum and kept in a 12-hour light / dark cycle.

[0089]Experiment protocol: Four groups (six mice per group) were included in the following experiment.

Group A: Control mice, per oz. administration of 30 μl water.

Group B: Per oz. (PO) administrations of 1 mg of ETANERCEPT.

Group C: PO administrations of 0.1 mg of ETANERCEPT.

Group D: i.p administrations of 0.1 mg of ETANERCEPT.

[0090]Treatment was for six c...

example 2

Effect of ENBREL® (ETANERCEPT) in Concanvalin A (ConA) Model

Introduction:

[0092]Several animal models mimicking human liver injury are known to be applied for exploring the immunopathogenesis in liver diseases. However, an acceptable in vivo model for hepatitis C virus HCV does not exist, as HCV is a non cytopathic virus and its liver damage is immune mediated.

[0093]ConA induced hepatitis. The Concanvalin A (ConA) model is a widely utilized mouse model that mimics many aspects of human autoimmune hepatitis. ConA is a bean lectin, which when injected intravenously to mice, induces activation of lymphocytes in the liver. ConA induces massive liver necrosis in mice, simultaneously with the lymphocyte infiltration in the liver, high level of apoptotic hepatocytes and elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The activated lymphocytes in the liver injury were later on confirmed to be Natural Killer T (NKT) cells. Together with Kupffer cells, NKT c...

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PUM

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Abstract

This application describes a method of delivering a TNF antagonist molecule, in a biologically active form, to a subject in need thereof, the method comprising, orally or mucosally administering to the subject a therapeutically effective amount of a TNF antagonist molecule.This application further describes a method of treating, preventing or reducing the severity of obesity, the method comprising, administering to the subject a therapeutically effective amount of a TNF antagonist molecule.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Patent Application No. 61 / 773,314, filed Mar. 6, 2013, which is hereby incorporated by reference.BACKGROUND OF THE INVENTION[0002]Tumor necrosis factor (TNF), a naturally occurring cytokine, plays a central role in the inflammatory response and in immune injury. TNF is formed by the cleavage of a precursor transmembrane protein, forming soluble molecules, which aggregate to form trimolecular complexes. These complexes bind to receptors found on a variety of cells. The binding of TNF causes many pro-inflammatory effects, including release of other pro-inflammatory cytokines, such as interleukin IL-6, IL-8, and IL-1; release of matrix metalloproteinases; and upregulation of the expression of endothelial adhesion molecules, further amplifying the inflammatory and immune cascade by attracting leukocytes into extravascular tissues. TNF was found to have a main role in the pathogenesis of ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/715
CPCC07K14/7151A61K31/00A61K38/1793C07K2319/30Y02A50/30
Inventor ILAN, YARON
Owner HADASIT MEDICAL RES SERVICES & DEVMENT
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