Drug-containing implants and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2019105396-A1
Application number	US-201816174083-A
Country	US
Kind code	A1
Filing date	Oct 29, 2018
Priority date	Jan 12, 2004
Publication date	Apr 11, 2019
Grant date	—

Abstract

The present invention provides implants comprising a therapeutic drug and a polymer containing polylactic acid (PLA) and optionally polyglycolic acid (PGA). The present invention also provides methods of maintaining a therapeutic level of a drug in a subject, releasing a therapeutic drug at a substantially linear rate, and treating schizophrenia and other diseases and disorders, utilizing implants of the present invention.

First claim

What is claimed is:

1 . An implantable, long term delivery system for improving medication adherence in disorders associated with a likelihood of non-compliance, comprising: a therapeutic drug in an implantable, rod-shaped structure, wherein said rod-shaped structure further comprises a polymer, said polymer comprising polylactic acid (PLA) and optionally polyglycolic acid (PGA) in a PLA:PGA molar ratio between 50:50 and 100:0, thereby forming a long term delivery system for improving medication adherence in subjects having disorders associated with a likelihood of non-compliance.

2 . The implantable, long term delivery system of claim 1 , wherein said rod-shaped structure is removable throughout the period of drug delivery.

3 . The implantable, long term delivery system of claim 1 , wherein said therapeutic drug is present in an amount of 30%-60% of the mass of said implant.

4 . The implantable, long term delivery system of claim 1 , wherein said therapeutic drug exhibits enhanced solubility in a reduced pH environment.

5 . The implantable, long term delivery system of claim 1 , wherein said therapeutic drug is risperidone, 9-OH-risperidone, or an active metabolite thereof.

6 . The implantable, long term delivery system of claim 1 , wherein therapeutic drug is thiothixene, haloperidol, hydrochlorothiazide (HCTZ), corticosterone, ibuprofen, aspirin, or an active metabolite thereof.

7 . The implantable, long term delivery system of claim 1 , wherein said PLA:PGA molar ratio is between 75:25 and 100:0.

8 . The implantable, long term delivery system of claim 1 , wherein said therapeutic drug is an anti-depressant.

9 . The implantable, long term delivery system of claim 1 , wherein said therapeutic drug is an anti-anxiety agent.

10 . The implantable, long term delivery system of claim 1 , wherein said therapeutic drug is an anti-psychotic agent.

11 . The implantable, long term delivery system of claim 1 , wherein said therapeutic drug is a birth control drug.

12 . The implantable, long term delivery system of claim 1 , wherein said implant has a surface area to volume ratio between 1 and 4 (millimeters [mm]) 2 /mm 3 .

13 . The implantable, long term delivery system of claim 1 , wherein said implant has a length between 1-3 centimeters.

14 . The implantable, long term delivery system of claim 1 , wherein said implant has a diameter between 2-4 millimeters.

15 . A biodegradable implant comprising a therapeutic drug and a polymer, said polymer comprising polylactic acid (PLA) and optionally polyglycolic acid (PGA) in a PLA:PGA molar ratio between 50:50 and 100:0, wherein said therapeutic drug is present in an amount of 10%-60% of the mass of said implant, and said polymer is present in an amount of 40%-90% of the mass of said implant.

16 . The biodegradable implant of claim 15 , wherein said implant is rod-shaped.

17 . The biodegradable implant of claim 15 , wherein said implant has a substantially circular cross-section.

18 . The biodegradable implant of claim 15 , wherein said implant has a substantially elliptical cross-section.

19 . The biodegradable implant of claim 15 , wherein said implant has a surface area to volume ratio between 1 and 4 (millimeters [mm]) 2 /mm 3 .

20 . The biodegradable implant of claim 15 , wherein said implant has a length between 1-3 centimeters.

21 . The biodegradable implant of claim 15 , wherein said implant has a diameter between 2-4 millimeters.

22 . The biodegradable implant of claim 15 , wherein said PLA:PGA molar ratio is between 75:25 and 100:0.

23 . The biodegradable implant of claim 15 , wherein said implant is removable throughout the period of drug delivery.

24 . The biodegradable implant of claim 15 , wherein said implant exhibits a reduced pH internal environment.

25 . The biodegradable implant of claim 24 , wherein said reduced pH internal environment facilitates the release of a drug with enhanced solubility at reduced pH.

26 . The biodegradable implant of claim 15 , wherein said implant is manufactured by a process comprising a step selected from solvent casting, melt-mixing, or a melt mix extrusion method that does not require use of a surfactant or an emulsion.

27 . The biodegradable implant of claim 15 , wherein said therapeutic drug is present in an amount of 30%-60% of the mass of said implant

28 . The biodegradable implant of claim 15 , wherein said therapeutic drug is risperidone, 9-OH-risperidone, or an active metabolite thereof.

29 . The biodegradable implant of claim 15 , wherein therapeutic drug is thiothixene, haloperidol, hydrochlorothiazide (HCTZ), corticosterone, ibuprofen, aspirin, or an active metabolite thereof.

30 . The biodegradable implant of claim 15 , wherein said therapeutic drug is an anti-depressant.

31 . The biodegradable implant of claim 15 , wherein said therapeutic drug is an anti-anxiety agent.

32 . The biodegradable implant of claim 15 , wherein said therapeutic drug is an anti-psychotic agent.

33 . The biodegradable implant of claim 15 , wherein said therapeutic drug is a birth control drug.

34 . A method for treating a schizophrenia in a human, comprising administering the biodegradable implant of claim 14 to said human, thereby treating a schizophrenia in a human.

35 . A method for treating a bipolar disorder, dementia, delirium, agitation, impulse control disorder, or psychotic depression in a human, comprising administering the biodegradable implant of claim 14 5 o said human, thereby treating a bipolar disorder, dementia, delirium, agitation, impulse control disorder, or psychotic depression in a human.

36 . A method for treating a subject for a disorder associated with a likelihood of non-compliance, comprising administering to said subject a therapeutic drug in a long term delivery system, wherein said long term delivery system comprises an implantable, rod-shaped structure, said implantable, rod-shaped structure comprising the target therapeutic drug and a polymer, said polymer comprising polylactic acid (PLA) and optionally polyglycolic acid (PGA) in a PLA:PGA molar ratio between 50:50 and 100:0, such that said subject is treated for said disorder associated with a likelihood of non-compliance.

37 . The method of claim 36 , wherein said subject is human.

38 . The method of claim 36 , wherein said step of administering is reversible throughout the period of drug delivery.

39 . The method of claim 36 , wherein said therapeutic drug is present in an amount of 30%-60% of the mass of said individual biodegradable implants

40 . The method of claim 36 , wherein said therapeutic drug is risperidone, 9-OH-risperidone, or an active metabolite thereof.

41 . The method of claim 36 , wherein said PLA:PGA molar ratio is between 85:15 and 100:0.

42 . The method of claim 36 , wherein said rod-shaped structure has a surface area to volume ratio between 1 and 4 (millimeters [mm]) 2 /mm 3 .

43 . The method of claim 36 , wherein said rod-shaped structure has a length between 1-3 centimeters.

44 .

Assignees

• Univ Pennsylvania

Inventors

• Siegel Steven
• Winey Karen

Classifications

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/4515

  having a butyrophenone group in position 1, e.g. haloperidol (pipamperone A61K31/4545) · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K9/1647

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title