Methods for treating ocular conditions with cyclic lipid contraining microparticles

• US 20060182781A1
• Filed: 03/06/2006
• Published: 08/17/2006
• Est. Priority Date: 04/30/2004
• Status: Abandoned Application

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Welty, Devin F., Chang-Lin, Joan-En, Hughes, Patrick
• Application Number:
  US11/368,845
• Publication Number:
  US 20060182781A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 9/00781 Apparatus for modifying intraocular pressure, e.g. for glaucoma treatment drainage implants in general A61M27/002
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)

Abstract

Biocompatible microparticles include a ophthalmically active cyclic lipid component and a biodegradable polymer that is effective, when placed into the subconjunctival space, in facilitating release of the cyclic lipid component into the anterior and posterior segments of an eye for an extended period of time. The cyclic lipid component can be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the cyclic lipid component can be encapsulated by the polymeric component. The present microparticles include oil-in-oil emulsified microparticles. The subconjunctivally administered microparticles can be used to treat or to reduce at least one symptom of an ocular condition, such as glaucoma or age related macular degeneration.

Claims

1. A method of treating an ocular condition comprising administering subconjunctivally to an eye microparticles comprising an ophthalmically active cyclic lipid component, thereby treating the ocular condition.

2. The method of claim 1, wherein the microparticles can release the lipid component for at least about one week after the administering step.

3. The method of claim 1, wherein the microparticles can release a therapeutically effective amount of the lipid component for at least about one week after the administering step.

4. The method of claim 1, wherein the microparticles comprise a polymer matrix.

5. The method of claim 1, wherein the microparticles comprise a biodegradable polymer matrix.

6. The method of claim 1, wherein the lipid component is selected from the group consisting of prostaglandins, prostaglandin analogs, and mixtures thereof.

7. The method of claim 1 wherein the lipid component is selected from the group consisting of non-acid cyclic lipid components.

8. The method of claim 7 wherein the lipid component is selected from the group consisting of prostamides and non-acidic prostaglandin analogs, and mixtures thereof.

9. The method of claim 8 wherein the lipid component is selected from the group consisting of prostamides, prostamide analogs, and mixtures thereof.

10. The method of claim 1 wherein the lipid component is selected from the group consisting of bimatoprost, bimatoprost analogs, latanoprost, latanoprost analogs, travoprost, travoprost analogs, unoprostone, unoprostone analogs, prostaglandin E1 and prostaglandin E1 analogs, prostaglandin E2 and prostaglandin E2 analogs, and mixtures thereof.

11. The method of claim 10 wherein the lipid component is selected from the group consisting of bimatoprost, bimatoprost analogs, and mixtures thereof.

12. The method of claim 1 wherein the microparticles have an average greatest dimension in a range of from about 5 μ

m to about 1 mm.

13. The method of claim 12 wherein the microparticles comprise a polymer matrix.

14. The method of claim 4 wherein the microparticles comprise from about 1% to about 99% by weight of the polymer matrix.

15. The method of claim 4 wherein the cyclic lipid component comprises from about 0.1% to about 90% by weight of the microparticles.

16. The method of claim 1 wherein the lipid component comprises a compound having the following formula (I)

17. The method of claim 16 wherein the lipid component comprises a compound having the following formula (II)

18. The method of claim 17 wherein the lipid component comprises a compound having the following formula (III)

19. The method of claim 18 wherein the lipid component comprises a compound having the following formula (IV)

20. The method of claim 19 wherein the lipid component comprises a compound having the following formula (V)

21. The method of claim 20 wherein Z is ═

O and X is selected from the group consisting of NH₂ or OCH₃.

22. The method of claim 21 wherein Y is 0, Z is =O and X is selected from the group consisting of alkoxy and amido radicals.

23. The method of claim 1 wherein the lipid component comprises a compound selected from the group consisting of:

a) cyclopentane heptenol-5-cis-2-(3α

-hydroxy-5-phenyl-1-trans-pentenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

b) cyclopentane heptenamide-5-cis-2-(3α

-hydroxy-5-phenyl-1-trans-pentenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

c) cyclopentane N,N-dimethylheptenamide-5-cis-2-(3α

-hydroxy-5-phenyl-1-trans-penten-yl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

d) cyclopentane heptenyl methoxide-5-cis-2-(3α

-hydroxy-5-phenyl-1-trans-pentenyl)-3-,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

e) cyclopentane heptenyl ethoxide-5-cis-2-(3α

-hydroxy-4-meta-chloro-phenoxy-1-trans--butenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

f) cyclopentane heptenylamide-5-cis-2-(3α

-hydroxy-4-meta-chloro-phenox-y-1-trans-butenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

g) cyclopentane heptenylamide-5-cis-2-(3α

-hydroxy-4-meta-tr-ifluoromethyl-phenoxy-1-trans-butenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

h) cyclopentane N-isopropyl hepteneamide-5-cis-2-(3α

-hydroxy-5-phenyl-1-trans-pentenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

i) cyclopentane N-ethyl heptenamide-5-cis-2-(3α

-hydroxy-5-phenyl-1-trans-pentenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

j) cyclopentane N-methyl heptenamide-5-cis-2-(3α

-hydroxy-5-phenyl-1-trans-pentenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

k) cyclopentane heptenol-5-cis-2-(3α

-hydroxy-4-meta-chlorophenoxy-1-trans-butenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

];

l) cyclopentane heptenamide-5-cis-2-(3α

-hydroxy-4-m-chlorophenoxy-1-trans-butenyl)-3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

], and

m) cyclopentane heptenol-5-cis-2-(3α

-hydroxy-5-phenylpentyl)3,5-dihydroxy, [1α

, 2β

, 3α

, 5α

].

24. The method of claim 23 wherein the lipid component comprises cyclopentane N-ethyl heptenamide-5-cis2-cis-2-(3α

-hydroxy-5-phenyl-1-trans-pentenyl)-3,5-dihydroxy, [1α

,2β

,3α

,5α

].

25. The method of claim 1 wherein the lipid component comprises a compound having the following formula (VI)

26. The method of claim 25 wherein the lipid component comprises a compound having the following formula (VII)

27. The method of claim 26 wherein the lipid component comprises a compound having the following formula (VII)

28. The method of claim 27 wherein the lipid component comprises a compound having the following formula (VIII)

29. The method of claim 28 wherein the lipid component comprises a compound having the following formula (IX)

30. The method of claim 29 wherein the lipid component comprises a compound having the following formula (X).

31. The method of claim 30 wherein the compound comprises prostaglandin E1.

32. The method of claim 30 wherein the compound comprises prostaglandin E2.

33. The method of claim 5 wherein the polymer matrix comprises a mixture or copolymer 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.

34. The method of claim 33 wherein the polymer matrix comprises a mixture of a two different polylactic acids.

35. The method of claim 33 wherein the polymer matrix comprises a mixture of a polylactic acid and a polylactide-co-glycolide.

36. The method of claim 5 wherein the polymer matrix comprises a mixture of different biodegradable polymers, each polymer having a different inherent viscosity.

37. The method of claim 5 wherein the polymer matrix comprises a mixture of different biodegradable polymers, each polymer having different molecular weights.

38. A method of treating an ocular condition characterized by high intraocular pressure comprising the subconjunctival delivery of microparticles comprising an ophthalmically active cyclic lipid component.

39. The method of claim 38 wherein the cyclic lipid component comprises a compound selected from the group consisting of bimatoprost, latanoprost, travoprost, unoprostone, prostaglandin E1, prostaglandin E2, prostaglandin F2α

, and salts, derivatives, analogs and mixtures of these.

40. The method of claim 39 wherein the cyclic lipid comprises bimatoprost or a salt, derivative, or an analog thereof.

41. A method of treating an ocular condition characterized by neurodegeneration comprising the subconjunctival delivery of microparticles comprising an ophthalmically active cyclic lipid component.

42. The method of claim 41 wherein the cyclic lipid component comprises a compound selected from the group consisting of bimatoprost, latanoprost, travoprost, unoprostone, prostaglandin E1, prostaglandin E2, prostaglandin F2α

, and salts, derivatives, analogs and mixtures of these.

43. The method of claim 42 wherein the cyclic lipid comprises bimatoprost or a salt, derivative, or an analog thereof.

44. The method of claim 42 wherein the cyclic lipid comprises prostaglandin E1 or a salt, derivative, or an analog thereof.

45. The method of claim 42 wherein the cyclic lipid comprises prostaglandin E2 or a salt, derivative, or an analog thereof.