IP Library Granted Patent US 8,475,829
Granted Patent B2
US 8,475,829 · App. 11/784,526 · Granted Jul 2, 2013

Implants for the treatment of dopamine associated states

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Quick Facts
Patent No.
US 8,475,829
App. No.
11/784,526
Granted
Jul 2, 2013
Kind
B2
Abstract

Biodegradable implants comprising dopamine modulating compounds are described.

Claims (42)

1. A method for treating a subject for a dopamine associated state, comprising administering to said subject a biodegradable implant, wherein said implant comprises a homogenous mixture of at least one biodegradable polymer and an effective amount of a dopamine modulating compound, such that said subject is treated for said dopamine associated state, wherein said implant comprises a biodegradable hydrophobic coating disposed about the homogenous mixture, such that the drug is delivered gradually rather than with an initial burst and is effective to maintain an effective plasma level for at least a desired delivery period.

2. The method of claim 1 , 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.

3. The method of claim 2 , wherein said dopamine associated state is Parkinson's disease.

4. The method of claim 1 , 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 claim 1 , 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 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 claim 8 , 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 claim 1 , 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 claim 1 , 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 claim 1 , 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 claim 1 , wherein at least one symptom of Parkinson's disease is treated.

23. The method of claim 1 , wherein said hydrophobic coating is PLA.

24. The method of claim 15 , wherein said polymer is PLA.

25. A method for treating a subject for Parkinson's disease, comprising administering to said subject a biodegradable implant, wherein said implant comprises a homogenous mixture of at least one biodegradable polymer and an effective amount of ropinirole, such that said subject is treated for Parkinson's disease, wherein said implant comprises a biodegradable hydrophobic coating disposed about the homogenous mixture, and wherein said implant releases ropinirole after implantation such that a plasma level of between about 1 ng/mL and about 40 ng/mL in said subject is maintained for at least three months.

26. The method of claim 25 , wherein said hydrophobic coating is polycaprolactone.

27. A method for treating a subject for a dopamine associated state, comprising administering to said subject a biodegradable implant, wherein said implant comprises a homogenous mixture of at least one biodegradable polymer and an effective amount of a dopamine modulating compound, such that said subject is treated for said dopamine associated state, wherein said implant comprises a biodegradable hydrophobic coating disposed about the homogenous mixture, wherein said dopamine modulating 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, and 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 week.

28. The method of claim 27 , wherein said implant releases about 0.3% of said dopamine modulating compound per day.

29. The method of claim 28 , wherein said plasma level is maintained for at least nine months.

30. The method of claim 28 , wherein said hydrophobic coating comprises polycaprolactone (PCL).

31. The method of claim 27 , wherein said implant releases about 0.4% of said dopamine modulating compound per day.

32. The method of claim 31 , wherein said plasma level is maintained for at least six months.

33. The method of claim 31 , wherein said hydrophobic coating comprises polyglycolide/polylactide co polymer (PLGA).

34. The method of claim 27 , wherein said dopamine modulating compound of formula (I) is ropinirole.

Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNOR'S EXECUTION DATE PREVIOUSLY RECORDED AT REEL: 035391 FRAME: 0471. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Aug 28, 2015
From: TEVA PHARMACEUTICALS INTERNATIONAL GMBH
To: NUPATHE INC.
Reel/Frame 036503/0154 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 13, 2015
From: TEVA PHARMACEUTICALS INTERNATIONAL GMBH
To: NUPATHE INC.
Reel/Frame 035391/0471 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 6, 2015
From: NUPATHE INC.
To: TEVA PHARMACEUTICALS INTERNATIONAL GMBH
Reel/Frame 035338/0416 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 24, 2008
From: SEBREE, TERRI B.
To: NUPATHE INC.
Reel/Frame 021579/0678 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 24, 2008
From: SIEGEL, STEVEN J.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 021579/0696 →