Methods for treating retinopathy with extended therapeutic effect

• US 20060233859A1
• Filed: 12/02/2005
• Published: 10/19/2006
• Est. Priority Date: 04/30/2004
• Status: Abandoned Application

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Whitcup, Scott M., Weber, David A.
• Application Number:
  US11/292,544
• Publication Number:
  US 20060233859A1
• 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 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• 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: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators

Abstract

Methods for treating and preventing retinopathic conditions by administering a glucocorticoid to the vitreous chamber of a patient at risk of, or suffering from, the retinopathy.

Claims

17. A method of preventing the presentation of at least one symptom of a retinopathy comprising administering to the vitreous of a mammal at risk of such presentation a glucocorticoid at a dosage effective to reduce the severity of such symptom in a different patient suffering from the retinopathy, comprising administering the dosage to the vitreous of a patient'"'"'s eye before the presentation of the at least one symptom.

1. A method for treating a retinopathy, the method comprising the steps of:

a) administering to the posterior chamber of an eye of a patient having a retinopathy a glucocorticoid capable of reducing the severity or progression of at least one symptom of the retinopathy;

b) permitting substantially all of the glucocorticoid to dissolve in the vitreous of the eye, and;

c) obtaining a continued reduction in the severity or progression of the at least one symptom at a time after a therapeutic amount of the glucocorticoid has ceased to be present in the posterior chamber.

2. The method of claim 1 wherein the at least one symptom is selected from the group consisting of increased anterior chamber flare, increased retinal vascular leakage, increased retinal vascular dilation, increased foveal thickness, a changed optic nerve cup volume, and a decreased electroretinography (ERG) value.

3. The method of claim 1 wherein the glucocorticoid is selected from the group consisting of dexamethasone, betamethasone, triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone hexacetonide, beclomethasone, dipropionate, beclomethasone dipropionate monohydrate, flumethasone pivalate, diflorasone diacetate, fluocinolone acetonide, fluorometholone, fluorometholone acetate, clobetasol propionate, desoximethasone, fluoxymesterone, fluprednisolone, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone cypionate, hydrocortisone probutate, hydrocortisone valerate, cortisone acetate, paramethasone acetate, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, prednisolone, prednisolone acetate, prednisolone sodium phosphate, prednisolone tebutate, clocortolone pivalate, flucinolone, dexamethasone 21-acetate, betamethasone 17-valerate, isoflupredone, 9-fluorocortisone, 6-hydroxydexamethasone, dichlorisone, meclorisone, flupredidene, doxibetasol, halopredone, halometasone, clobetasone, diflucortolone, isoflupredone acetate, fluorohydroxyandrostenedione, beclomethasone, flumethasone, diflorasone, clobetasol, cortisone, paramethasone, clocortolone, prednisolone 21-hemisuccinate free acid, prednisolone metasulphobenzoate, prednisolone terbutate, triamcinolone acetonide 21-palmitate, prednisolone, flurometholone, medrysone, loteprednol, fluazacort, betamethasone, prednisone, methylprednisolone, triamcinolone hexacatonide, paramethasone acetate, diflorasone, fluocinolone and fluocinonide, derivatives thereof, salts thereof, and mixtures thereof.

4. The method of claim 3 wherein said glucocorticoid is selected from the group consisting of dexamethasone and triamcinolone, derivatives thereof, salts thereof, and mixtures thereof.

5. The method of claim 1 wherein the glucocorticoid is administered in conjunction with a biodegradable implant comprising the glucocorticoid and a biodegradable polymer associated therewith.

6. The method of claim 5 wherein substantially all therapeutically effective amounts of the glucocorticoid are released from the implant within 30 days following the administration.

7. The method of claim 5 wherein substantially all therapeutically effective amounts of the glucocorticoid are released from the implant within 45 days following the administration.

8. The method of claim 5 wherein substantially all therapeutically effective amounts of the glucocorticoid are released from said implant within 60 days following the administration.

9. The method of claim 1 wherein a continued reduction in the severity or progression of the at least one symptom continues for at least 45 days following the administration of the glucocorticoid.

10. The method of claim 1 wherein a continued reduction in the severity or progression of the at least one symptom continues for at least 60 days following the administration of the glucocorticoid.

11. The method of claim 1 wherein a continued reduction in the severity or progression of the at least one symptom continues for at least 90 days following the administration of the glucocorticoid.

12. The method of claim 1 wherein a continued reduction in the severity or progression of the at least one symptom continues for at least 120 days following the administration of the glucocorticoid.

13. The method of claim 1 wherein the glucocorticoid is injected directly into the vitreous chamber of the eye.

14. The method of claim 13 wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 30 days following the administration.

15. The method of claim 13 wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of said eye within 45 days following the administration.

16. The method of claim 13 wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 60 days following the administration.

18. The method of claim 17 wherein the at least one symptom is selected from the group consisting of increased anterior chamber flare, increased retinal vascular leakage, increased retinal vascular dilation, increased foveal thickness, an altered optic nerve cup volume, and decreased ERG values.

19. The method of claim 17 wherein the glucocorticoid is selected from the group consisting of dexamethasone, betamethasone, triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone hexacetonide, beclomethasone, dipropionate, beclomethasone dipropionate monohydrate, flumethasone pivalate, diflorasone diacetate, fluocinolone acetonide, fluorometholone, fluorometholone acetate, clobetasol propionate, desoximethasone, fluoxymesterone, fluprednisolone, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone cypionate, hydrocortisone probutate, hydrocortisone valerate, cortisone acetate, paramethasone acetate, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, prednisolone, prednisolone acetate, prednisolone sodium phosphate, prednisolone tebutate, clocortolone pivalate, flucinolone, dexamethasone 21-acetate, betamethasone 17-valerate, isoflupredone, 9-fluorocortisone, 6-hydroxydexamethasone, dichlorisone, meclorisone, flupredidene, doxibetasol, halopredone, halometasone, clobetasone, diflucortolone, isoflupredone acetate, fluorohydroxyandrostenedione, beclomethasone, flumethasone, diflorasone, clobetasol, cortisone, paramethasone, clocortolone, prednisolone 21-hemisuccinate free acid, prednisolone metasulphobenzoate, prednisolone terbutate, triamcinolone acetonide 21-palmitate, prednisolone, flurometholone, medrysone, loteprednol, fluazacort, betamethasone, prednisone, methylprednisolone, triamcinolone hexacatonide, paramethasone acetate, diflorasone, fluocinolone and fluocinonide, derivatives thereof, salts thereof, and mixtures thereof.

20. The method of claim 19 wherein the glucocorticoid is selected from the group consisting of dexamethasone and triamcinolone, derivatives thereof, salts thereof, and mixtures thereof.

21. The method of claim 17 wherein said glucocorticoid is administered in conjunction with a biodegradable implant comprising the glucocorticoid and a biodegradable polymer associated therewith.

22. The method of claim 21 wherein substantially all therapeutically effective amounts of the glucocorticoid are released from said implant within 30 days following the administration.

23. The method of claim 21 wherein substantially all therapeutically effective amounts of the glucocorticoid are released from said implant within 45 days following the administration.

25. The method of claim 21 wherein substantially all therapeutically effective amounts of the glucocorticoid are released from said implant within 60 days following the administration.

26. The method of claim 17 wherein a significant presentation of the at least one symptom does not occur for at least 60 days following the administration of the glucocorticoid.

27. The method of claim 17 wherein a significant presentation of the at least one symptom does not occur for at least 90 days following the administration of the glucocorticoid.

28. The method of claim 17 wherein a significant presentation of the at least one symptom does not occur for at least 120 days following the administration of the glucocorticoid.

29. The method of claim 17 wherein the glucocorticoid is injected directly into the vitreous chamber of the eye.

30. The method of claim 29 wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 30 days following the administration.

31. The method of claim 29 wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 45 days following the administration.

32. The method of claim 29 wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 60 days following the administration.

25-1. The method of claim 17 wherein a significant presentation of the at least one symptom does not occur for at least 45 days following the administration of the glucocorticoid.