Compositions comprising 15-hepe and/or 15-hetre and methods of treating or preventing cardiometabolic disease, metabolic syndrome, and/or related diseases

A 15-HEPE, metabolic syndrome technology, applied in metabolic diseases, drug combinations, urinary system diseases, etc., can solve problems such as increased risk of heart disease

Inactive Publication Date: 2021-06-08
AFIMMUNE LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These conditions increase the risk of heart disease

Method used

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  • Compositions comprising 15-hepe and/or 15-hetre and methods of treating or preventing cardiometabolic disease, metabolic syndrome, and/or related diseases
  • Compositions comprising 15-hepe and/or 15-hetre and methods of treating or preventing cardiometabolic disease, metabolic syndrome, and/or related diseases
  • Compositions comprising 15-hepe and/or 15-hetre and methods of treating or preventing cardiometabolic disease, metabolic syndrome, and/or related diseases

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0358] Example 1: Renal interstitial fibrosis caused by unilateral ureteral obstruction

[0359] The purpose of this study was to examine the effects of DS109(15-HETrE) and DS102(15-HEPE) on UUO-induced renal interstitial fibrosis.

[0360] figure 1 The study design is depicted from surgery and treatment to study day 14.

[0361] 1.1 Materials and methods

[0362] Test substances: The test substances in this study are DS109 (15-HETrE) and DS102 (15-HEPE). To prepare dosing solutions for each substance, DS109 was first weighed and then dissolved in a vehicle of 0.5% hydroxypropylmethylcellulose (HPMC), and DS102 was diluted in a vehicle of 0.5% HPMC.

[0363] UUO surgery: On study day 0, mice underwent UUO surgery under pentobarbital sodium anesthesia. The mice were first shaved, and then the abdomen was incised to remove the mouse's left ureter from the abdomen. Using 4-0 nylon sutures, the ureter was ligated at two points. The peritoneum and skin of the mouse were then...

example 2

[0413] Example 2: Biliary Ligation (BDL) Study in Cholestatic Liver Disease and / or Hepatic Fibrosis

[0414] The aim of this study was to examine the effect of DS012 on BDL-induced cholestasis.

[0415] Figure 9 The study design is depicted from surgery and treatment to study day 14.

[0416] 1.1 Materials and methods

[0417] Test substance: The test substance in this study is DS102. To prepare dosing solutions for each substance, DS102 was diluted in a vehicle of 0.5% hydroxypropylmethylcellulose (HPMC).

[0418] BDL surgery: On study day 0, BDL surgery was performed under pentobarbital (Kyoritsu Seiyaku, Japan) anesthesia. Firstly, the mouse hair was shaved, the abdominal cavity was cut open, and the common bile duct was ligated twice with 7-0 surgical silk. The peritoneum and skin of the mouse are closed with sutures, and the mouse is transferred to a clean cage (eg, a rest cage) until recovery from anesthesia. The common bile ducts of sham-operated mice were expose...

example 3

[0466] Example 3: Effect of DS102 on TGF-beta receptor, signaling and induced fibrotic proteins

[0467] The aim of this study was to investigate the effects of 15-HEPE and 15-HEPE EE on TGF-β receptor expression, TGF-β-induced intracellular signaling, and pro-fibrotic epithelial-mesenchymal transition proteins.

[0468] 1.1 Materials and methods

[0469] Cytotoxicity test: The cytotoxicity of 15-HEPE free acid and ethyl ester was tested in different liver (hepatocarcinoma) cell lines to understand the concentration range in the test system.

[0470]Transcriptional activity: A promoter (luciferase) assay was performed to measure TGFβ-induced transcriptional activation following 15-HEPE administration.

[0471] Identification of sucrose-induced 15-HEPE-induced microdomain translocation of TGF-β receptors using sucrose gradient ultracentrifugation and confocal microscopy. TGF-β receptor activation was performed in the plasma membrane of Mv1Lu cells (mink lung epithelial cells)...

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Abstract

The present disclosure relates to methods of treating or preventing metabolic syndrome and / or cardiometabolic disease by administration of 15-HEPE, 15-HETrE, or compositions thereof.

Description

[0001] priority claim [0002] This application claims priority to U.S. Provisional Application No. 62 / 848,222, filed May 15, 2019, the entire contents of which are hereby incorporated by reference. technical field [0003] The present application generally relates to compositions comprising 15-HEPE and / or 15-HETrE, and to methods of using the same. Background technique [0004] Cardiometabolic disease, also known as metabolic syndrome, is a group of conditions including elevated blood pressure, high blood sugar, impaired glucose tolerance, excess body fat and abnormal lipid levels that occur together and increase heart disease , stroke and diabetes risks. These conditions lead to an increased risk of heart disease. Contents of the invention [0005] The present application relates to compositions comprising 15-HEPE and / or 15-HETrE and methods of using such compositions to treat various diseases and conditions. [0006] In some aspects, the present disclosure provides ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P3/10A61K31/202
CPCA61P3/10A61K31/202A61P1/16A61P13/02
Inventor J·克莱麦克斯D·考夫兰
Owner AFIMMUNE LTD
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