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. A pharmaceutical preparation comprising an oligomer of formula (I)
wherein
n is 2 or 3, R 1 is hydroxyl, R 2 is an alcohol radical (—OR 5 ), and R 5 is a C 1-24 alkyl radical, with the proviso that when n is 2, R 5 is not methyl; or
n is 3, R 1 is hydroxyl, R 2 is an amine radical (—NR 3 R 4 ) wherein 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; or
n is 2 or 3, R 1 is an alcohol radical (—OR 5 ), R 5 is a C 1-24 alkyl radical, and R 2 is an amine radical (—NR 3 R 4 ) wherein 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, or
n is 2 or 3, R 1 and R 2 are independently chosen from alcohol radicals (—OR 5 ), wherein R 5 is a C 1-24 alkyl radical and wherein R 1 and R 2 are different
and at least one excipient.
2. A pharmaceutical preparation according to claim 1 wherein the carbonyl groups carrying the radicals R 1 and R 2 are arranged as substituents in the trans position to each adjacent substituent.
3. A pharmaceutical preparation according to claim 1 wherein the oligomer of formula (I) is represented by formula (II)
4. A pharmaceutical preparation according to claim 1 wherein the oligomer of formula (I) is represented by formula (III)
5. A pharmaceutical preparation according to claim 1 , said pharmaceutical preparation being available in a form suitable for oral, rectal, transdermal, dermal, opthalmological, nasal, pulmonary or parenteral application.
6. A pharmaceutical preparation according to claim 1 , 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.
7. A pharmaceutical preparation according to claim 6 , said pharmaceutical preparation being present in the form of nano-particles, micro-pellets or micro-tablets.
8. A pharmaceutical preparation according to claim 6 wherein the solid oral dosage forms further comprise an enteric coating.
9. A pharmaceutical preparation according to any of the claims 1 to 8 which contains an amount of an oligomer corresponding to 10 to 500 mg of fumaric acid.
10. A method for preparing a pharmaceutical preparation comprising admixing an oligomer of formula (I)
wherein
n is 2 or 3, R 1 is hydroxyl, R 2 is an alcohol radical (—OR 5 ), and R 5 is a C 1-24 alkyl radical, with the proviso that when n is 2, R 5 is not methyl; or
n is 3, R 1 is hydroxyl, R 2 is an amine radical (—NR 3 R 4 ) wherein 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; or
n is 2 or 3, R 1 is an alcohol radical (—OR 5 ), R 5 is a C 1-24 alkyl radical, and R 2 is an amine radical (—NR 3 R 4 ) wherein 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, or
n is 2 or 3, R 1 and R 2 are independently chosen from alcohol radicals (—OR 5 ), wherein R 5 is a C 1-24 alkyl radical and wherein R 1 and R 2 are different
with at least one excipient.
11. A pharmaceutical preparation according to claim 7 , wherein said nano-particles, micro-pellets or micro-tablets are filled in sachets or capsules.
12. A method for preparing a pharmaceutical preparation according to claim 10 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.
13. A method for preparing a pharmaceutical preparation according to claim 12 , wherein said tablets, granulates, nano-particles, nano-capsules, micro-capsules, micro-tablets, pellets, or powders are enterically coated.
14. A method for preparing a pharmaceutical preparation according to claim 12 , wherein said nano-particles, nano-capsules, micro-capsules, micro-tablets, pellets, or powders are put into capsules.
15. A pharmaceutical preparation comprising an oligomer of formula (I)
wherein n is 2 or 3, R 1 is hydroxyl, R 2 is an alcohol radical (—OR 5 ), and R 5 is a C 1-24 alkyl radical, with the proviso that when n is 2, R 5 is not methyl
and at least one excipient.
16. A pharmaceutical preparation comprising an oligomer of formula (I)
wherein n is 3, R 1 is hydroxyl, R 2 is an amine radical (—NR 3 R 4 ), and 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,
and at least one excipient.
17. A pharmaceutical preparation comprising an oligomer of formula (I)
wherein n is 2 or 3, R 1 is an alcohol radical (—OR 5 ), R 5 is a C 1-24 alkyl radical, and R 2 is an amine radical (—NR 3 R 4 ), wherein 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,
and at least one excipient.