Hypotensive lipid-containing biodegradable intraocular implants and related methods

• US 20050244464A1
• Filed: 04/30/2004
• Published: 11/03/2005
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Hughes, Patrick M.
• Granted Patent: US 7,799,336 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

Biocompatible intraocular implants include a prostamide component and a biodegradable polymer that is effective in facilitating release of the prostamide component into an eye for an extended period of time. The prostamide component may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. The implants may be placed in an eye to treat or reduce a at least one symptom of an ocular condition, such as glaucoma.

Claims

1. A biodegradable intraocular implant comprising:

a prostamide component and a biodegradable polymer matrix that releases drug at a rate effective to sustain release of a therapeutically effective amount of the prostamide component for at least about one week after the implant is placed in an eye.

2. The implant of claim 1, wherein the prostamide component comprises a single type of a prostamide derivative.

3. The implant of claim 1, wherein the prostamide component comprises at least one prostamide derivative selected from the group consisting of bimatoprost, salts thereof, and mixtures thereof.

4. The implant of claim 1, wherein the prostamide component consists essentially of bimatoprost.

5. The implant of claim 1, wherein the prostamide component comprises a combination of two or more different prostamide derivatives.

6. The implant of claim 5, wherein the prostamide component comprises a combination of bimatoprost and iatanoprost.

7. The implant of claim 5, wherein the prostamide component comprises a combination of bimatoprost and travoprost.

8. The implant of claim 1, wherein the prostamide component comprises bimatoprost, and the implant further comprises a beta-adrenergic receptor antagonist.

9. The implant of claim 8, wherein the beta-adrenergic receptor antagonist is timolol.

10. The implant of claim 1, wherein the prostamide component comprises bimatoprost and the implant further comprises a carbonic anhydrase inhibitor.

11. The implant of claim 10, wherein the carbonic anhydrase inhibitor is dorzolamide.

12. The implant of claim 1, wherein the prostamide component is dispersed within the biodegradable polymer matrix.

13. The implant of claim 1, wherein the prostamide component comprises bimatoprost provided in an amount of about 0.1% to about 90% by weight of the implant.

14. The implant of claim 1, wherein the prostamide component comprises a compound having the formula (I)

15. The implant of claim 14, wherein the compound of the prostamide component has the following formula (II)

16. The implant of claim 15, wherein the compound has the following formula (III)

17. The implant of claim 16, wherein the compound has the following formula (IV)

18. The implant of claim 17, wherein the compound has the following formula (V)

19. The implant of claim 1, wherein the matrix comprises a mixture of two different biodegradable polymers, each polymer selected from the group consisting of polylactic acid, polyglycolic acid, polylactide-co-glycolide, derivatives thereof, and mixtures thereof.

20. The implant of claim 19, wherein the matrix comprises a mixture of two different polylactic acids.

21. The implant of claim 19, wherein the matrix comprises a mixture of a polylactic acid and a polylactide-co-glycolide.

22. The implant of claim 1, wherein the matrix comprises a mixture of different biodegradable polymers, each biodegradable polymer having a different inherent viscosity.

23. The implant of claim 1, wherein the matrix comprises a mixture of different biodegradable polymers, each polymer having a different molecular weight.

24. The implant of claim 1, wherein the matrix releases drug at a rate effective to sustain release of an amount of the prostamide component from the implant for more than one month from the time the implant is placed in the vitreous of the eye.

25. The implant of claim 1, wherein the prostamide component comprises bimatoprost, and the matrix releases drug at a rate effective to sustain release of a therapeutically effective amount of bimatoprost for about three months.

26. The implant of claim 1, wherein the therapeutically effective amount of the prostamide component is an amount effective to stimulate aqueous humor outflow in the eye in which the implant is placed.

27. The implant of claim 1, further comprising a prostaglandin analog.

28. The implant of claim 27, wherein the prostaglandin analog is unoprostone.

29. The implant of claim 1, further comprising an intraocular pressure lowering drug other than a prostamide derivative.

30. The implant of claim 1, wherein the implant is structured to be placed in the vitreous of the eye.

31. The implant of claim 1 which is formed by an extrusion process.

32. A method of making a biodegradable intraocular implant, comprising the step of:

extruding a mixture of a prostamide component and a biodegradable polymer component to form a biodegradable material that releases drug at a rate effective to sustain release of an amount of the prostamide component from the implant in an eye in which the implant is placed.

33. The method of claim 32, wherein the prostamide component comprises at least one prostamide derivative selected from the group consisting of bimatoprost, salts thereof, and mixtures thereof.

34. The method of claim 32, wherein the prostamide component consists essentially of bimatoprost.

35. The method of claim 32, further comprising a step of mixing the prostamide component with the polymer component before the extrusion step.

36. The method of claim 32, wherein the prostamide component and the polymer component are in a powder form.

37. The method of claim 32, wherein the polymer component comprises a mixture of two different biodegradable polymers, each polymer selected from the group consisting of polylactic acid, polyglycolic acid, polylactide-co-glycolide, derivatives thereof, and mixtures thereof.

38. The method of claim 32, wherein the polymer component comprises a mixture of two different biodegradable polymers, each biodegradable polymer having a different inherent viscosity.

39. A method of treating an ocular condition in an eye of a patient, comprising the step of placing a biodegradable intraocular implant in an eye of the patient, the implant comprising a prostamide component and a biodegradable polymer matrix that releases drug at a rate effective to sustain release of an amount of the prostamide component from the implant to provide an amount of the prostamide component effective to prevent or reduce a symptom of the ocular condition of the eye.

40. The method of claim 39, wherein the method is effective to treat glaucoma.

41. The method of claim 39, wherein the placement of the implant in the eye is effective in reducing intraocular pressure in the eye.

42. The method of claim 39, wherein the implant is placed in the posterior of the eye.

43. The method of claim 39, wherein the implant is placed in the eye using a trocar.

44. The method of claim 39, wherein the implant is placed in the eye using a syringe.

45. The method of claim 39, further comprising a step of administering a therapeutic agent in addition to the prostamide component to the patient.

46. The method of claim 39, wherein the prostamide component comprises at least one prostamide selected from the group consisting of bimatoprost, a derivative thereof, salts thereof, and mixtures thereof.

47. The method of claim 39, wherein the placement of the implant in the eye is effective in increasing aqueous humor outflow.

48. The method of claim 47, wherein the release of the prostamide component is effective for at least two weeks after placement in the eye.