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Composition comprising at least to compounds which induces indolamine 2,3 - dioxygenase (IDO), for the treatment of an autoimmune disorder or suffering from immune rejection of organs

a technology of dioxygenase and indolamine, which is applied in the field of compound comprising at least two compounds, can solve problems such as inconvenient us

Inactive Publication Date: 2013-11-21
IDOGEN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent relates to a combination of different compounds that can induce IDO, which is an enzyme that has beneficial effects in treating various diseases. By using a mixture of these compounds, the amount of IDO is increased more than the sum of what each compound alone would have achieved. This combination can be used to produce a pharmaceutical composition for treating mammals, including humans, with IDO-induced diseases. The patent also describes a method for treating mammals with this combination and a method for inducing IDO in cell cultures. Overall, this patent provides a novel approach for creating effective treatments for IDO-related diseases.

Problems solved by technology

However, many of these substances increase the amount of IDO to levels which are too low to be suitable in pharmaceutical composition, and will thus require, to induce effective IDO levels, high doses that are not suitable for reasons of toxicology, compliance or costs.

Method used

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  • Composition comprising at least to compounds which induces indolamine 2,3 - dioxygenase (IDO), for the treatment of an autoimmune disorder or suffering from immune rejection of organs
  • Composition comprising at least to compounds which induces indolamine 2,3 - dioxygenase (IDO), for the treatment of an autoimmune disorder or suffering from immune rejection of organs
  • Composition comprising at least to compounds which induces indolamine 2,3 - dioxygenase (IDO), for the treatment of an autoimmune disorder or suffering from immune rejection of organs

Examples

Experimental program
Comparison scheme
Effect test

example 1

Synergistic Effect on IDO Expression by Zebularine and Interferon Gamma

Materials and Methods

[0063]THP-1 (ATCC: TIB-202) is a human monocytic cell line that originates from an acute monocytic leukemia. It has the phenotype of monocytes but can be differentiated to a more dendritic phenotype. In the current study, the THP-1 cells were in vitro passaged in RPMI 1640 medium supplemented with 5% or 10% FCS, 10 mM Hepes, 1 mM Sodium pyruvate, and 50 ug / ml gentamicin (R5 or R10 medium respectively). The cell density was adjusted to 200 000 cells per ml, and the cultures were incubated for four to seven days at 37° C. with 10% CO2 in a humidified incubator. The substance, or combination of substances, being studied, were added to the medium at specified time points and in the case of IFN-gamma removed from medium as indicated. 96-168 hours after initiation of treatment, the IDO expression was assessed by PCR or by Quantitative PCR (Roche). RNA was extracted from cells cultured in flasks or ...

example 2

Synergistic Effect on IDO Expression by Interferon Gamma and Valproic Acid

[0068]Materials and methods used were the same as described in Example 1 above. Cells of the human monocytic cell line THP-1 were non-exposed (medium control), exposed to interferon gamma alone (200 IU / ml), valproic acid (Sigma) alone (1 mM) or to the combination (FIG. 2A). The results of THP-1 cells exposed to the combination demonstrate a synergistic effect. Similar experiments but with the valproic acid concentration reduced to 0.5 mM was also performed (FIG. 2B). A synergistic effect on IDO1 expression was demonstrated also with this combination.

example 3

Synergistic Effect on IDO Expression by Zebularine, Interferon Gamma and Valproic Acid

[0069]Materials and methods used were the same as described in Example 1 above. Cells of the human monocytic cell line THP-1 were non-exposed (medium control), exposed to zebularine alone (100 uM), to interferon gamma alone (200 IU / ml) or valproic acid alone (1 mM) (FIG. 3). The THP-1 cells were exposed to the three substances pairwise and also with all three substances in combination. The scale is logaritmic and the relative values are given for each bar. The result clearly demonstrates a synergistic effect of all the three substances on the IDO1 expression in THP-1 cells.

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Abstract

A composition and method for using a composition, the composition having at least two compounds, each of which induces indolamine 2,3-dioxygenase, for the treatment of an autoimmune disorder or disease or immune rejection of transplants or gene therapeutically modified cells, wherein the inducers have different mechanism of action and wherein the composition gives rise to a synergistic effect on the IDO levels.

Description

FIELD OF INVENTION[0001]The invention relates to the use of a composition comprising at least two compounds, each of which induces indolamine 2,3-dioxygenase, for the treatment of an autoimmune disorder or disease or immune rejection of transplants or gene therapeutically modified cells, wherein said inducers have different mechanism of action and wherein the composition gives rise to a synergistic effect on the IDO levels.BACKGROUND OF INVENTION[0002]Indoleamine dioxygenase (IDO) degrades the indole moiety of tryptophan and initiates the production of neuroactive and immunoregulatory metabolites, collectively known as kynurenines. The functional expression of IDO by dendritic cells has emerged in recent years as a major mechanism of peripheral tolerance. IDO contributes to maternal tolerance in pregnancy, control of allograft rejection, and protection against autoimmunity, inflammatory pathology and allergy. IDO expression also serves a physiological mechanism by which malignancies...

Claims

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Application Information

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IPC IPC(8): A61K38/24A61K38/18A61K31/19A61K38/21A61K31/7068
CPCA61K31/19A61K38/24A61K31/593A61K31/7068A61K45/06A61K31/56A61K38/212A61K38/1841A61K38/217A61K2300/00A61P1/04A61P1/16A61P1/18A61P3/10A61P3/12A61P5/14A61P5/50A61P7/06A61P9/00A61P9/10A61P15/00A61P15/08A61P17/00A61P17/04A61P17/06A61P17/14A61P19/02A61P21/04A61P25/00A61P25/02A61P25/28A61P27/16A61P29/00A61P31/10A61P37/00A61P37/06A61P37/08A61P43/00Y02A50/30
Inventor SALFORD, LEIFSJOGREN, HANS OLOVWIDEGREN, BENGT
Owner IDOGEN