RU2002127782A

RU2002127782A - COMPOSITIONS CONTAINING L-DOPA TRANSFER BLOCKS IN KIDNEY CELLS, AND THEIR APPLICATION FOR TREATMENT OF PARKINSON'S DISEASE

Info

Publication number: RU2002127782A
Application number: RU2002127782/15A
Authority: RU
Inventors: Патрисью СУАРЕС-ДА-СИЛВА
Original assignee: Портела Энд Компанья С.А.
Priority date: 2000-03-14
Filing date: 2001-03-13
Publication date: 2004-04-20

Claims

1. Pharmacological composition for the treatment of Parkinson's disease, containing L-dopa, and at least one compound selected from phenylbenzopyran derivatives, trans-stilbene derivatives or 3- (4-hydroxyphenyl) -1- (2,4,6- trihydroxyphenyl) -1-propanone (phloretin).

2. The composition according to claim 1, characterized in that the phenylbenzopyran derivative is a flavonoid.

3. The composition according to claim 2, characterized in that the flavonoid has the General formula

in which groups X are the same or different and are selected from H and OH;

the Y groups are the same or different and are selected from H and OR, where R is H, CH ₃ and CH ₂ -Ph, including the corresponding 3-C ₆ H ₅ (Y ₄ ) derivatives.

4. The composition according to claim 1, characterized in that the trans-stilbene derivative has the general formula

in which the X groups are the same or different and represent H or OH.

5. The composition according to claim 1, characterized in that the blockers are selected from the group consisting of

5,7-dihydroxy-2- (4-methoxyphenyl) -4H-1-benzopyran-4-one (acacetin),

5,7-dihydroxy-2- (4-hydroxyphenyl) -4H-1-benzopyran-4-one (apigenin),

5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baikalein),

5,7-dihydroxy-2-phenyl-4H-1-benzopyran-4-one (chrysin),

([2R, 3R]) - 2- [3,4-dihydroxyphenyl] -3,4-dihydro-1 [2H] benzopyran-3,5,7-triol ((-) - epicatechin),

2- (3,4-dihydroxyphenyl) -3,7-dihydroxy-4H-1-benzopyran-4-one (fisetin),

5,7-dihydroxy-3- (4-hydroxyphenyl) -4H-1-benzopyran-4-one (genistein),

3,5,7-trihydroxy-2- (4-hydroxyphenyl) -4H-1-benzopyran-4-one (camferol),

2- (2,4-dihydroxyphenyl) -3,5,7-trihydroxy-4H-1-benzopyran-4-one (morin),

3,5,7-trihydroxy-2- (3,4,5-trihydroxyphenyl) -4H-1-benzopyran-4-one (myricetin),

3- (4-hydroxyphenyl) -1- (2,4,6-trihydroxyphenyl) propanone (phloretin),

2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-4H-1-benzopyran-4-one (quercetin),

2- (3,4-dihydroxyphenyl) -3,5,6,7-tetrahydroxy-4H-1-benzopyran-4-one (quercetagetin),

4’-benzyloxy-3 ’, 5’-dimethoxy-3,5,7-trihydroxyflavone,

3,7-dihydroxy-3 ’, 4’, 5’-trimethoxy flavone, 3 ’, 4’, 7,8-tetrahydroxy flavone,

3,5,7-trihydroxy-3 ’, 4’, 5’-trimethoxy flavone,

3.3 ’, 4,5’-tetrahydroxy-trans-stilbene (pizetannol), trans-4-styrylphenol and

3.4 ’, 5’-trihydroxy-trans-stilbene (resveratrol).

6. The composition according to any one of claims 1, 4 or 5, characterized in that the blocker is resveratrol.

7. The composition according to any one of claims 1 to 6, characterized in that it further comprises an amino acid decarboxylase enzyme inhibitor and / or a catechol-o-methyl transferase enzyme inhibitor.

8. The composition according to claim 7, characterized in that said decarboxylase inhibitor is benserazide or carbidofu, and said catechol-o-methyltransferase inhibitor is entacapone or tolcapone.

9. The composition according to any one of claims 1 to 8, characterized in that it further comprises inert, pharmaceutically acceptable excipients.

10. The use of a composition according to any one of claims 1 to 9 for the preparation of a preparation for treating or preventing the progression of any form of Parkinson's disease.

11. L-DOPA external transfer blocker in renal cells selected from the group consisting of phenylbenzopyran derivatives, trans-stilbene derivatives or 3- (4-hydroxyphenyl) -1- (2,4,6-trihydroxyphenyl) -1-propanone ( phloretin), in combination with L-DOPA for use in therapy with sequential or simultaneous administration.

12. The blocker according to claim 11, characterized in that it is selected from blockers according to claims 2-6.

13. The use of at least one L-DOPA external transfer blocker in renal cells selected from the group consisting of phenylbenzopyran derivatives, trans-stilbene derivatives or 3- (4-hydroxyphenyl) -1- (2,4,6- trihydroxyphenyl) -1-propanone (phloretin), for the preparation of a drug for the treatment or prevention of the progression of any form of Parkinson's disease by sequential or simultaneous administration with L-DOPA.

14. The use of at least one blocker of external L-dopa transfer in renal cells selected from the group consisting of phenylbenzopyran derivatives, trans-stilbene derivatives or 3- (4-hydroxyphenyl) -1- (2,4,6- trihydroxyphenyl) -1-propanone (phloretin), for the preparation of a drug for the treatment of motor disorders by modifying the dopaminergic activity of the cellular structure of the tract connecting the black substance with the striatum, and by sequential or simultaneous administration with L-dopa.

15. The use according to claims 13 or 14, characterized in that at least one blocker is selected from blockers according to any one of claims 2 to 6.

16. The use according to any one of paragraphs.13-15, characterized in that the blocker is present in an amount that provides approximately 40-30000 μg / kg per dose.

17. The use according to any one of paragraphs.13-16, characterized in that the treatment also includes simultaneous or sequential administration of an amino acid decarboxylase inhibitor or a catechol-o-methyltransferase inhibitor.

18. The use according to claim 17, wherein the decarboxylase inhibitor is benserazide or carbidofu, and the methyltransferase inhibitor is entacapone or tolcapone.

19. The use of the composition of claims 1-6, for the preparation of a drug for the treatment of Parkinson's disease by blocking peripheral decarboxylation sequentially or simultaneously administered L-DOPA.

20. A method of treating Parkinson's disease, comprising administering to a subject in need of such treatment, simultaneously or sequentially with L-DOPA, a therapeutically effective amount of at least one blocker of external L-DOPA transfer in renal cells selected from the group consisting of derivatives phenylbenzopyran derivatives of trans-stilbene or 3- (4-hydroxyphenyl) -1- (2,4,6-trihydroxyphenyl) -1-propanone (phloretin).

21. A method for regulating motor disorders by modifying the dopaminergic activity of the cellular structure of a pathway that binds a black substance with a striatum, which consists in administering to a subject in need of such regulation, in consecutive or simultaneous combination with L-DOPA, a therapeutically effective amount of at least one blocker external transport of L-dopa in renal cells selected from the group consisting of phenylbenzopyran derivatives, trans-stilbene derivatives or 3- (4-hydroxyphenyl) -1- (2,4,6-trihydride oxyphenyl) -1-propanone (phloretin).

22. A method of increasing the levels of introduced L-DOPA in the bloodstream of a subject, comprising administering to the subject an effective amount of at least one blocker of external L-DOPA transfer in renal cells selected from the group consisting of phenylbenzopyran derivatives, trans-stilbene derivatives, or 3 - (4-hydroxyphenyl) -1- (2,4,6-trihydroxyphenyl) -1-propanone (phloretin).

23. A method for increasing the bioavailability of administered L-DOPA in brain tissues of a subject, comprising administering to the subject an effective amount of at least one blocker of external L-DOPA transfer in renal cells selected from the group consisting of phenylbenzopyran derivatives, trans-stilbene derivatives or 3- (4-hydroxyphenyl) -1- (2,4,6-trihydroxyphenyl) -1-propanone (phloretin).

24. The method according to any one of claims 20 to 23, characterized in that it further comprises administering an aromatic L-amino acid decarboxylase inhibitor or a catechol-o-methyl transferase inhibitor.