Carbocyclic and oxacarbocyclic fumaric acid oligomers
View Patent ↗The present invention relates to certain carbocyclic and oxacarbocyclic fumaric acid oligomers and the use thereof for preparing a pharmaceutical preparation as well of pharmaceutical preparations containing these compounds.
1. An oxacarbocyclic fumaric acid oligomer of the following formula (IV)
wherein the radicals R 1 and R 2 are the same or different and are independently chosen from amine radicals (—NR 3 R 4 ), amino acid radicals (—NH—CH(COOH)-R 6 ), peptide radicals having 2 to 100 amino acids, alcohol radicals (—OR 5 ) and a hydroxyl radical,
n is an integer from 2 to 10,
the radicals R 3 and R 4 are the same or different and are independently chosen from hydrogen, C 1-24 alkyl radicals, a phenyl radical and C 6-10 aralkyl radicals,
the radical R 5 is chosen from hydrogen, C 1-24 alkyl radicals, a phenyl radical and C 6-10 aralkyl radicals,
and the radical R 6 represents a side chain of a natural or synthetic amino acid.
2. An oligomer according to claim 1 , wherein the radicals R 3 , R 4 , and R 5 are the same or different and are independently chosen from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, t-butyl, pentyl, cyclopentyl, 2-ethyl hexyl, hexyl, cyclohexyl, heptyl, cycloheptyl, octyl, vinyl, allyl, 2-hydroxyethyl, 2- or 3-hydroxypropyl, 2,3-dihydroxypropyl, 2-methoxyethyl, methoxymethyl and 2- or 3-methoxypropyl.
3. An oligomer according to claim 1 , wherein R 1 represents an amine radical and R 2 is chosen from alkoxy radicals (—OR 5 ) and —OH.
4. An oligomer according to claim 1 , wherein R 1 and R 2 are independently chosen from alkoxy radicals (—OR 5 ) and a hydroxyl radical.
5. An oligomer according to claim 4 , wherein R 1 and R 2 are independently chosen from methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, phenoxy, and pentoxy.
6. An oligomer according to claim 4 wherein R 1 and R 2 are both methoxy.
7. An oxacarbocyclic oligomer according to claim 1 represented by the formula (V)
8. An oxacarbocyclic oligomer according to claim 1 represented by the formula (IV)
wherein R 1 and R 2 are as defined in claim 1 .
9. A pharmaceutical preparation comprising an oligomer of formula (IV):
wherein the radicals R 1 and R 2 are the same or different and are independently chosen from amine radicals (—NR 3 R 4 ), amino acid radicals (—NH—CH(COOH)-R 6 ), peptide radicals having 2 to 100 amino acids, alcohol radicals (—OR 5 ) and a hydroxyl radical,
n is an integer from 2 to 10,
the radicals R 3 and R 4 are the same or different and are independently chosen from hydrogen, C 1-24 alkyl radicals, a phenyl radical and C 6-10 aralkyl radicals,
the radical R 5 is chosen from hydrogen, C 1-24 alkyl radicals, a phenyl radical and C 6-10 aralkyl radicals,
and the radical R 6 represents a side chain of a natural or synthetic amino acid;
and at least one excipient.
10. A pharmaceutical preparation according to claim 9 , said pharmaceutical preparation being available in a form suitable for oral, rectal, transdermal, dermal, ophthalmological, nasal, pulmonary or parenteral application.
11. A pharmaceutical preparation according to claim 9 , said pharmaceutical preparation being present in the form of tablets, coated tablets, capsules, granulate, solutions for drinking, liposomes, nano-particles, nano-capsules, micro-capsules, micro-tablets, pellets, powders, granulate filled in capsules, micro-tablets filled in capsules, pellets filled in capsules, nano-particles filled in capsules or powder filled in capsules.
12. A pharmaceutical preparation according to claim 11 , said pharmaceutical preparation being present in the form of nano-particles, micro-pellets or micro-tablets.
13. A pharmaceutical preparation according to claim 11 further comprising an enteric coating.
14. A pharmaceutical preparation according to claim 9 , comprising an amount of fumaric acid oligomer corresponding to 10 to 500 mg of fumaric acid.
15. A method for preparing a pharmaceutical preparation comprising admixing an oligomer of formula (IV):
wherein the radicals R 1 and R 2 are the same or different and are independently chosen from amine radicals (—NR 3 R 4 ), amino acid radicals (—NH—CH(COOH)-R 6 ), peptide radicals having 2 to 100 amino acids, alcohol radicals (—OR 5 ) and a hydroxyl radical,
n is an integer from 2 to 10,
the radicals R 3 and R 4 are the same or different and are independently chosen from hydrogen, C 1-24 alkyl radicals, a phenyl radical and C 6-10 aralkyl radicals,
the radical R 5 is chosen from hydrogen, C 1-24 alkyl radicals, a phenyl radical and C 6-10 aralkyl radicals,
and the radical R 6 represents a side chain of a natural or synthetic amino acid,
with at least one excipient.
16. A method for preparing a pharmaceutical preparation according to claim 15 further comprising subjecting the admixture to tabletting, direct compression, melt methods, or spray drying to form tablets, granulates, nano-particles, nano-capsules, micro-capsules, micro-tablets, pellets, or powders.
17. A method for preparing a pharmaceutical preparation according to claim 16 , wherein said tablets, granulates, nano-particles, nano-capsules, micro-capsules, micro-tablets, pellets, or powders are enterically coated.
18. A method for preparing a pharmaceutical preparation according to claim 15 , wherein said nano-particles, nano-capsules, micro-capsules, micro-tablets, pellets, or powders are put into capsules.