Reverse micelle system comprising metal ions and use thereof
The present invention relates to reverse micelle system based on sterols, acylglycerols, phospholipids or sphingolipids and metal ions. Reverse micelle system of the invention is able to cross mucosa and cellular membranes. It thus allows vectorization of metal ions to target sites. It is advantageously useful in the pharmaceutical and dietetic fields.
1. A reverse micelle system comprising 150-1500 μg/ml of at least one metal ion, a sterol, an acylglycerol, lecithin, an alcohol and water, wherein the weight ratio of lecithin to acylglycerol is from 0.05 to 0.40.
2. The reverse micelle system according to claim 1 , wherein the micelles have aqueous cores of: a) 4 nm; b) from 3 to 5 nm; c) from 3.5 to 5 nm; or d) from 3.7 to 4.5 nm.
3. The reverse micelle system according to claim 1 , obtainable by the following method:
(a) contacting (i) a sterol, (ii) an acylglycerol, (iii) lecithin, (iv) an alcohol, (v) water, and (vi) at least one metal ion, and
(b) stirring the mixture obtained in (a) at 40° C. or less for a time sufficient to obtain formation of reverse micelles.
4. The reverse micelle system according to claim 1 , wherein the weight ratio of sterol/acylglycerol ranges from 0.015 to 0.05 or from 0.03 to 0.04.
5. The reverse micelle system according to claim 3 , wherein the stirring of step (b) is carried out at a temperature ranging from 15° C. to 40° C., from 25° C. to 40° C., or from 30° C. to 37° C.
6. The reverse micelle system according to claim 1 , wherein the acylglycerol is selected from the group consisting of 1,2-diolein and 1-oleoyl-2-acetyl glycerol.
7. The reverse micelle system according to claim 1 , wherein the sterol is sitosterol or cholesterol.
8. The reverse micelle system according to claim 1 , wherein the metal ion is selected from the group consisting of lithium, zinc, niobium, vanadium, selenium, molybdenum, chromium, antimony, tin, gold, ruthenium, palladium, platinum, strontium, arsenic, manganese and mixtures thereof.
9. A pharmaceutical composition comprising a reverse micelle system according to claim 1 and at least a pharmaceutically acceptable carrier, excipient or support.
10. The pharmaceutical composition according to claim 9 , wherein the metal ion is lithium.
11. The pharmaceutical composition according to claim 9 , wherein the metal ion is vanadium.
12. The pharmaceutical composition according to claim 9 , wherein the metal ion is strontium.
13. The pharmaceutical composition according to claim 9 , wherein the metal ion is manganese.
14. The pharmaceutical composition according to claim 9 , wherein the metal ions in the reverse micelle system cross the blood brain barrier.
15. A method for the delivery of at least one metal ion to a mammal, wherein said method comprises mucosal administration to said mammal of the pharmaceutical composition according to claim 9 .
16. A method for the treatment or improvement of the symptoms of a disease or disorder selected from pathologies of the central nervous system (CNS), neurodegenerative diseases, autoimmune diseases, type 2 diabetes, insulin resistance, metabolic syndrome, cancers, respiratory tumors, acute promyelocytic leukemia, acquired immunodeficiency syndromes, osteoporosis, diseases linked to oxidative stress, bipolar disorders, depression, and inflammatory disorders, wherein said method comprises administration to a mammal in need of such treatment and/or improvement of the pharmaceutical composition according to claim 9 .
17. The method according to claim 16 , wherein the disease or disorder is selected from pathologies of the CNS and neurodegenerative diseases.
18. The method according to claim 16 , wherein the disease or disorder is selected from type 2 diabetes, insulin resistance and metabolic syndrome.
19. The method according to claim 16 , wherein the disease or disorder is osteoporosis.
20. The method according to claim 16 , wherein the disease or disorder is selected from disorders linked to oxidative stress.
21. The method according to claim 16 , wherein the disease or disorder is selected from genetic, tumoral, viral and degenerative diseases in the central nervous system.
22. The reverse micelle system according to claim 8 , wherein the metal ion is arsenic.
23. The reverse micelle system according to claim 1 , said reverse micelle system consisting of 150-1500 μg/ml of at least one metal ion, a sterol, an acylglycerol, lecithin, an alcohol and water, wherein the weight ratio of lecithin to acylglycerol is from 0.05 to 0.40.
24. The reverse micelle system according to claim 1 , wherein the water is present in an amount, by weight, ranging from 5 g to 15 g per 100 ml total volume of said system.
25. The reverse micelle system according to claim 1 , wherein the alcohol is present in an amount, by weight, ranging from 5 g to 12 g per 100 ml total volume of said system.
26. The reverse micelle system according to claim 1 , wherein the water is present in an amount, by weight, ranging from 5 g to 15 g per 100 ml total volume of said system and the alcohol is present in an amount, by weight, ranging from 5 g to 12 g per 100 ml total volume of said system.
27. The reverse micelle system of claim 1 , wherein the system comprises 180 μg/ml of at least one metal ion.
28. The reverse micelle system of claim 1 , wherein the system comprises 300 μg/ml of at least one metal ion.
29. The reverse micelle system of claim 1 , wherein the system comprises 600 μg/ml of at least one metal ion.
30. The pharmaceutical composition according to claim 10 , wherein the composition comprises 150-1200 μg/ml of lithium.
31. The pharmaceutical composition according to claim 30 , wherein the composition comprises 600 μg/ml of lithium.
32. The reverse micelle system of claim 1 , wherein the acylglycerol has the following formula (I):
in which:
R 1 is an acyl residue of a linear or branched, saturated or unsaturated fatty acid having between 14 and 24 carbon atoms, a hydrogen atom, or a mono-, di- or tri-galactose or glucose;
R 2 is an acyl residue of a linear or branched, saturated or unsaturated fatty acid having between 2 and 18 carbon atoms; and
R 3 is an acyl residue of a linear or branched, saturated or unsaturated fatty acid having between 14 and 24 carbon atoms, or a hydrogen atom.
33. The reverse micelle system of claim 1 , wherein the acylglycerol has the following formula (I):
in which:
R 1 is an acyl residue of a linear or branched, saturated or unsaturated fatty acid having between 14 and 24 carbon atoms or a hydrogen atom;
R 2 is an acyl residue of a linear or branched, saturated or unsaturated fatty acid having between 2 and 18 carbon atoms; and
R 3 is a hydrogen atom.