Compounds and compositions comprising such compounds for the prevention or treatment of dyslipidaemias

Patent metadata

Field	Value
Publication number	US-2016256429-A1
Application number	US-201415028139-A
Country	US
Kind code	A1
Filing date	Oct 8, 2014
Priority date	Oct 8, 2013
Publication date	Sep 8, 2016
Grant date	—

Abstract

The present invention relates to the field of medicine. It more particularly relates to the use of compounds for preventing and/or treating dyslipidemia in a subject, said dyslipidemia typically being linked to the excess presence in the biological membranes, including in the biological membranes of non-adipocyte cells, of fatty acids, in particular of saturated long-chain fatty acids, and/or of sterols. The invention also relates to compositions, in particular pharmaceutical compositions and food supplements or complements, comprising such compounds, and to the uses thereof for preventing and/or treating dyslipidemia. The compounds and compositions according to the invention can in particular be advantageously used for preventing and/or treating a pathological condition selected from metabolic syndrome and/or a symptom or abnormality characteristic of metabolic syndrome, preferably for preventing or treating type 2 diabetes mellitus or hepatic steatosis.

First claim

1 - 12 . (canceled)

13 . A method for treating or reducing the risk of dyslipidemia linked to the excess presence in biological membranes in a subject comprising a step of administering to the subject a compound comprising a polar head comprising at least one hydroxyl residue on which is grafted a single unsaturated fatty acid comprising between 16 and 24 carbon atoms and having 1 to 6 unsaturation(s) in the cis configuration, and wherein said compound i) does not allow the production of diunsaturated phospholipids in the membrane of the treated cells and ii) does not constitute a source of oleic acid for the treated cell.

14 . The method according to claim 13 , characterized in that dyslipidemia is responsible for the intoxication (lipointoxication) of non-adipocyte cells at the origin of the dysfunction or of the apoptosis of said non-adipocyte cells by decreasing or suppressing the fluidity of the plasma membrane thereof and/or of the organelle membranes thereof.

15 . The method according to claim 13 , characterized in that the compound is nontoxic to cells unable to synthesize neutral lipids, typically triglycerides and/or esterified sterols.

16 . The method according to claim 13 , characterized in that the polar head of the compound is of formula (1):

wherein:
A is an oxygen atom or an NR 1 group, with R 1 =H, or a C 1 -C 6 alkyl optionally substituted with OH,
n=2 or 3, and
R is any chemical group and can be different from one (CHR) group to another.

17 . The method according to claim 13 , characterized in that the compound is selected from the group consisting of mannide monooleate, 3-hydroxy-2,2-bis(hydroxymethyl)propyl oleate and N,N-diethanololeamide.

18 . The method according to claim 13 , characterized in that by restoring biological membrane fluidity, the compound treats or reduces the risk of dyslipidemia.

19 . The method according to claim 13 , where dyslipidemia is associated with the presence in said subject of metabolic syndrome.

20 . The method according to claim 19 , wherein said method treats or reduces the risk of at least one symptom of metabolic syndrome selected from insulin resistance, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, hypertension, heart failure and hepatic steatosis.

21 . The method according to claim 13 , wherein the method reduces the risk of developing or treats type 2 diabetes mellitus.

22 . The method according to claim 21 , wherein the method comprises administering said compound in combination with a biguanide, glitazone, sulfonamide-based hypoglycemic, glinide, DPP-4 inhibitor, incretin mimetic or α-glucosidase inhibitor.

23 . The method according to claim 13 , wherein said subject is an animal or human being.

24 . The method according to claim 13 , wherein said compound i) does not allow the production of diunsaturated phospholipids in the membrane of the treated cells, ii) does not constitute a source of oleic acid for the treated cell and iii) does not induce intracellular calcium mobilization and/or is not degraded by lipases.

25 . A composition comprising a compound comprising a polar head comprising at least one hydroxyl residue on which is grafted a single unsaturated fatty acid comprising between 16 and 24 carbon atoms and having 1 to 6 unsaturation(s) in the cis configuration, wherein said compound i) does not allow the production of diunsaturated phospholipids in the membrane of the treated cells and ii) does not constitute a source of oleic acid for the treated cell, said composition being selected from a pharmaceutical composition and a functional food or food supplement.

26 . The composition according to claim 25 , wherein said compound i) does not allow the production of diunsaturated phospholipids in the membrane of the treated cells, ii) does not constitute a source of oleic acid for the treated cell and iii) does not induce intracellular calcium mobilization and/or is not degraded by lipases.

Assignees

• Centre Nat Rech Scient
• Univ Poitiers
• Univ Exeter

Inventors

• Spanova Miroslava
• Ferreira Thierry
• Clement Romain
• Dhayal Shalinee
• Morgan Noël

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title