IMPLANTS FOR THE TREATMENT OF DOPAMINE ASSOCIATED STATES
Biodegradable implants comprising dopamine modulating compounds are described.
1 . A method for treating a subject for a dopamine associated state, comprising administering to said subject a biodegradable implant, wherein said implant comprises an effective amount of a dopamine modulating compound, such that said subject is treated for said dopamine associated state.
2 . The method of claim 1 , wherein said dopamine associated state is Parkinson's to disease, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism, pervasive development disorder (PDD), Asberger's syndrome, toxin-induced parkinsonism, disease-induced parkinsonism, erectile dysfunction, restless leg syndrome, or hyperprolactinemia.
3 . The method of claim 2 , wherein said dopamine associated state is Parkinson's disease.
4 . The method of any one of claims 1 - 3 , wherein said dopamine modulating compound is a dopamine agonist.
5 . The method of claim 4 , wherein said dopamine agonist is apomorphine, lisuride, pergolide, bromocriptine, pramipexole, rotigotine, docarpamine, terguride, cabergoline, levodopa, spheramine, romergoline, carmoxirole, zelandopam, sumanirole, sibenadet a 4-alkylamino-2(3H)-indolone compound or a combination thereof.
6 . The method of claim 5 , wherein said 4-alkylamino-2(3H)-indolone compound is of formula (I):
wherein:
R is amino, alkylamino, di-alkylamino, alkenylamino, dialkenylamino, N-alkyl-N-alkenylamino, benzylamino, dibenzylamino, arylalkylamino, or diarylalkylamino;
R 1 , R 2 and R 3 are each independently hydrogen or alkyl; and
n is 1, 2, or 3, and pharmaceutically acceptable salts thereof.
7 . The method of claim 6 , wherein said dopamine modulating compound is ropinirole.
8 . The method of any one of claims 1 - 7 , wherein said effective amount results in a plasma level of said dopamine modulating compound between about 1 ng/mL and about 40 ng/mL in said subject for at least one day.
9 . The method of claim 8 , wherein said effective amount results in a plasma level to of between about 1 ng/mL and about 20 ng/mL.
10 . The method of claim 9 , wherein said effective amount results in a plasma level of between about 1 ng/mL and about 15 ng/mL.
11 . The method of any one of claims 8 - 10 , wherein said plasma level of said dopamine modulating compound in said subject is maintained for at least one week.
12 . The method of claim 11 , wherein said plasma level is maintained for at least one month.
13 . The method of claim 12 , wherein said plasma level is maintained for at least three months.
14 . The method of claim 13 , wherein said plasma level is maintained for at least six or more months.
15 . The method of anyone of claims 1 - 14 , wherein said polymer comprises poly(glycolic acid), poly-D,L-lactic acid, poly-L-lactic acid, copolymers of the foregoing, poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone, polydioxonone, poly(ortho carbonates), poly(acetals), poly(lactic acid-caprolactone), polyorthoesters, poly(glycolic acid-caprolactone), polyanhydrides, natural polymers, or mixtures thereof.
16 . The method of claim 15 , wherein said natural polymer is albumin, casein, or a wax.
17 . The method of any one of claims 1 - 16 , wherein said polymer is charged.
18 . The method of claim 15 , wherein said polymer is a polyglycolide/polylactide co polymer or polycaprolactone.
19 . The method of any one of claims 1 - 18 , wherein said implant comprises one or more sections.
20 . The method of claim 19 , wherein said implant comprises two or more sections.
21 . The method of claim 20 , wherein said sections have different rates of degradation.
22 . The method of any one of claims 1 - 21 , wherein at least one symptom of Parkinson's disease is treated.
23 . The method of any one of claims 1 - 22 , wherein said implant comprises a hydrophobic coating.
24 . The method of claim 23 , wherein said hydrophobic coating is PLA.
25 . The method of claim 15 , wherein said polymer is PLA.
26 . A biodegradable implant, comprising a dopamine modulating compound and a biodegradable polymer.
27 . The implant of claim 26 , wherein said dopamine modulating compound is a dopamine agonist.
28 . The implant of claim 27 , wherein said dopamine agonist is apomorphine, lisuride, pergolide, bromocriptine, pramipexole, rotigotine, docarpamine, terguride, cabergoline, levodopa, spheramine, romergoline, carmoxirole, zelandopam, sumanirole, sibenadet, a 4-alkylamino-2(3H)-indolone compound or a combination thereof.
29 . The implant of claim 28 , wherein said 4-alkylamino-2(3H)-indolone compound is of formula (I):
wherein:
R is amino, alkylamino, di-alkylamino, alkenylamino, dialkenylamino, N-alkyl-N-alkenylamino, benzylamino, dibenzylamino, arylalkylamino, or diarylalkylamino;
R 1 , R 2 and R 3 are each independently hydrogen or alkyl; and
n is 1, 2, or 3, and pharmaceutically acceptable salts thereof.
30 . The implant of claim 29 , wherein said dopamine modulating compound is ropinirole.
31 . The implant of anyone of claims 27 - 30 , wherein said polymer comprises poly(glycolic acid), poly-D,L-lactic acid, poly-L-lactic acid, copolymers of the foregoing, poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone, polydioxonone, poly(ortho carbonates), poly(acetals), poly(lactic acid-caprolactone), polyorthoesters, poly(glycolic acid-caprolactone), polyanhydrides, natural polymers, or mixtures thereof.
32 . The implant of claim 31 , wherein said polymer is a polyglycolide/polylactide co polymer or polycaprolactone.
33 . The implant of any one of claims 27 - 32 , wherein said dopamine modulating compound is present in an amount which is effective to treat a subject for a dopamine associated state.
34 . The implant of claim 33 , wherein said dopamine associated state is Parkinson's disease, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism, pervasive development disorder (PDD), Asberger's syndrome, toxin-induced parkinsonism, disease-induced parkinsonism, erectile dysfunction, restless leg syndrome, or hyperprolactinemia.
35 . The implant of any one of claims 27 - 34 , wherein said dopamine modulating compound is present in an amount which is effective to maintain a dopamine modulating compound level of between about 1 ng/ml and about 40 ng/ml in a subject for at least one day.
36 . The implant of claim 35 , wherein said dopamine modulating compound levels are maintained for at least one week.
37 . The implant of claim 36 , wherein said dopamine modulating compound levels are maintained for at least one month.
38 . The implant of claim 37 , wherein said dopamine modulating compound levels are maintained for at least three months.
39 . The implant of any one of claims 27 - 38 , wherein said implant comprises a hydrophobic coating.
40 . The implant of claim 39 , wherein said hydrophobic coating is PLA.
41 . The implant of claim 31 , wherein said polymer is PLA.
42 . The implant of any one of claims 27 - 41 , wherein said implant is manufactured using a melt mix procedure.
43 . A method for maintaining a plasma level of between about 1 and 40 of a dopamine modulating compound in a subject, comprising administering to said subject an implant comprising a biodegradable polymer and said dopamine modulating compound, such that the plasma level of said compound is maintained for at least one day.
44 . The method of claim 43 , wherein said plasma level is maintained for at least one month.
45 . The method of claim 44 , wherein said plasma level is maintained for at least three months.
46 . The method of any one of claims 43 - 45 , wherein said subject is suffering from a dopamine associated state selected from Parkinson's disease, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism, pervasive development disorder (PDD), Asberger's syndrome, toxin-induced parkinsonism, disease-induced parkinsonism, erectile dysfunction, restless leg syndrome, or hyperprolactinemia.
47 . The method of claim 46 , wherein said dopamine associated state is Parkinson's disease.
48 . The method of any one of claims 43 - 47 , wherein said dopamine modulating compound is a dopamine agonist.
49 . The method of claim 48 , wherein said dopamine agonist is apomorphine, lisuride, pergolide, bromocriptine, pramipexole, rotigotine, docarpamine, terguride, cabergoline, levodopa, spheramine, romergoline, carmoxirole, zelandopam, sumanirole, sibenadet, a 4-alkylamino-2(3H)-indolone compound, or a combination thereof.
50 . The method of claim 49 , wherein said a 4-alkylamino-2(3H)-indolone compound is of formula (I):
wherein:
R is amino, alkylamino, di-alkylamino, alkenylamino, dialkenylamino, N-alkyl-N-alkenylamino, benzylamino, dibenzylamino, arylalkylamino, or diarylalkylamino;
R 1 , R 2 and R 3 are each independently hydrogen or alkyl; and
n is 1, 2, or 3, and pharmaceutically acceptable salts thereof.
51 . The method of claim 50 , wherein said dopamine modulating compound is ropinirole.
52 . The method of anyone of claims 43 - 51 , wherein said polymer comprises poly(glycolic acid), poly-D,L-lactic acid, poly-L-lactic acid, copolymers of the foregoing, poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone, polydioxonone, poly(ortho carbonates), poly(acetals), poly(lactic acid-caprolactone), polyorthoesters, poly(glycolic acid-caprolactone), polyanhydrides, natural polymers, or mixtures thereof.
53 . The method of claim 52 , wherein said polymer is a polyglycolide/polylactide co polymer or polycaprolactone.
54 . The method of any one of claims 43 - 53 , wherein said implant comprises a hydrophobic coating.
55 . The method of claim 54 , wherein said hydrophobic coating comprises PLA.
56 . The implant of claim 52 , wherein said polymer is PLA.
57 . A method for treating a subject for Parkinson's disease, comprising administering to said subject a biodegradable implant, wherein said implant comprises an effective amount of ropinirole to treat Parkinson's disease.
58 . A biodegradable implant, comprising ropinirole and a biodegradable polymer.
59 . The implant of claim 58 , wherein said implant comprises a hydrophobic coating.