Triamcinolone compositions for intravitreal administration to treat ocular conditions

• US 20060141049A1
• Filed: 02/14/2006
• Published: 06/29/2006
• Est. Priority Date: 11/12/2003
• Status: Abandoned Application

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Whitcup, Scott M., Chang, James N., Trogden, John T., Lyons, Robert T.
• Application Number:
  US11/354,415
• Publication Number:
  US 20060141049A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears

Abstract

Triamcinolone compositions, and methods of using such compositions, useful for injection into the vitreous of human eyes are provided. Such compositions can include triamcinolone particles present in a therapeutically effective amount, a viscosity inducing component, and an aqueous carrier component. The compositions have viscosities of at least about 10 cps or about 100 cps at a shear rate of 0.1/second. In a preferred embodiment, the viscosity is in the range of from about 80,000 cps to about 300,000 cps. The compositions advantageously suspend the triamcinolone particles for prolonged periods of time.

Claims

1. A pharmaceutical composition for treating a posterior ocular condition, the composition comprising:

(a) a triamcinolone present in a therapeutically effective amount as a plurality of particles;

(b) a viscosity inducing component in an amount effective to increase the viscosity of the composition, and;

(c) an aqueous carrier component,

wherein the composition has a viscosity of at least about 10 cps at a shear rate of about 0.1/second and is injectable into the vitreous of a human eye.

2. The pharmaceutical composition of claim 1 injectable through a 27 gauge needle into the vitreous of a human eye.

3. The pharmaceutical composition of claim 1 wherein the triamcinolone particles are substantially uniformly suspended in the composition.

4. The pharmaceutical composition of claim 1, wherein the viscosity inducing component is a polymeric hyaluronate.

25. A method for treating a posterior ocular condition, the method comprising the step of administering the pharmaceutical composition of claim 1 to the vitreous of a human or animal, thereby treating the posterior ocular condition.

33. The pharmaceutical composition of claim 1 injectable through a 28 gauge needle into the vitreous of a human eye.

34. The pharmaceutical composition of claim 1 injectable through a 29 gauge needle into the vitreous of a human eye.

35. The pharmaceutical composition of claim 1 wherein the composition has a viscosity of at least about 300,000 cps at a shear rate of about 0.1/second and is injectable through a 30 gauge needle into the vitreous of a human eye.

5. A pharmaceutical composition for treating a posterior ocular condition, comprising:

(a) triamcinolone particles;

(b) polymeric hyaluronate, in which the triamcinolone particles are suspended;

(c) sodium chloride;

(d) sodium phosphate, and;

(e) water,

wherein the pharmaceutical composition has a viscosity at a shear rate of about 0.1/second of between about 128,000 cps and about 225,000 cps.

6. The pharmaceutical composition of claim 5, wherein the sodium phosphate present in the pharmaceutical composition comprises both monobasic sodium phosphate and dibasic sodium phosphate.

7. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises between about 2% w/v triamcinolone and about 8% w/v triamcinolone.

8. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises between about 2% w/v hyaluronate and about 3% w/v hyaluronate.

9. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises about 0.6% w/v sodium chloride.

10. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises between about 0.03% w/v sodium phosphate and about 0.04% w/v sodium phosphate.

38. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises between about 0.5% w/v hyaluronate and about 6% w/v hyaluronate.

39. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises between about 0.6% w/v sodium chloride to about 0.9% w/v sodium chloride.

40. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises between about 0.0% w/v sodium phosphate and about 0.1% w/v sodium phosphate.

11. A pharmaceutical composition for treating a posterior ocular condition, the pharmaceutical composition consisting essentially of:

(a) triamcinolone particles;

(b) polymeric hyaluronate, in which polymeric hyaluronate the triamcinolone particles are suspended;

(c) sodium chloride;

(d) sodium phosphate, and;

(e) water,

wherein the pharmaceutical composition has a viscosity at a shear rate 0.1/second of between about 128,000 cps and about 225,000 cps.

12. The pharmaceutical composition of claim 11, wherein the sodium phosphate present in the pharmaceutical composition is present as both monobasic sodium phosphate and dibasic sodium phosphate.

13. The pharmaceutical composition of claim 11, wherein the pharmaceutical composition has between about 2% w/v triamcinolone and about 8% w/v triamcinolone.

14. The pharmaceutical composition of claim 11, wherein the pharmaceutical composition has between about 2% w/v hyaluronate and about 3% w/v hyaluronate.

15. The pharmaceutical composition of claim 11, wherein the pharmaceutical composition has about 0.6% w/v sodium chloride.

16. The pharmaceutical composition of claim 11, wherein the pharmaceutical composition has about 0.3% w/v sodium phosphate.

17. The pharmaceutical composition of claim 11, wherein the pharmaceutical composition has between about 0.03% w/v sodium phosphate and about 0.04% w/v sodium phosphate.

18. A triamcinolone suspension for treating a posterior ocular condition, consisting of:

(a) triamcinolone particles;

(b) polymeric hyaluronate, in which the triamcinolone particles are suspended;

(c) sodium chloride;

(d) dibasic sodium phosphate heptahydrate;

(e) monobasic sodium phosphate monohydrate, and;

(f) water,

wherein the composition has a viscosity at a shear rate 0.1/second of between about 128,000 cps and about 225,000 cps.

19. The suspension of claim 18, wherein the sodium phosphate present in the suspension is present as both monobasic sodium phosphate and dibasic sodium phosphate.

20. The suspension of claim 18, wherein the suspension has between about 2% w/v triamcinolone and about 8% w/v triamcinolone.

21. The suspension of claim 18, wherein the suspension has between about 2% w/v hyaluronate and about 3% w/v hyaluronate.

22. The suspension of claim 18, wherein the suspension has between about 0.6% w/v sodium chloride.

23. The suspension of claim 18, wherein the suspension has about 0.3% w/v sodium phosphate.

24. The suspension of claim 18, wherein the suspension has between about 0.03% w/v sodium phosphate and about 0.04% w/v sodium phosphate.

26. The method of claim 26 wherein the administering step comprises intravitreal injecting.

27. A method for treating macula edema, the method comprising the step of administering to the vitreous of a human eye a pharmaceutical composition comprising:

(a) a triamcinolone, and;

(b) a hyaluronate,

wherein the pharmaceutical composition having a viscosity at a shear rate 0.1/second of between about 128,000 cps and about 225,000 cps.

28. A pharmaceutical composition for treating a posterior ocular condition, the composition comprising:

(a) a triamcinolone present in a therapeutically effective amount as a plurality of particles;

(b) a viscosity inducing component in an amount effective to increase the viscosity of the composition, and;

(c) an aqueous carrier component,

wherein the composition has a viscosity of at least about 10 cps at a shear rate of 0.1/second and is injectable into the vitreous of a human eye and wherein the pharmaceutical composition releases the triamcinolone with substantially first order release kinetics over a period of at least about 45 days after the intravitreal injection.

29. The pharmaceutical composition of claim 28, wherein the pharmaceutical composition exhibits:

(a) reduced generation of intraocular inflammation;

(b) no plume effect, and;

(c) cohesiveness, upon intravitreal injection of the pharmaceutical composition.

30. A method for treating a posterior ocular condition, the method comprising the step of intravitreal administration of a sustained release pharmaceutical composition implant comprising:

(a) a triamcinolone present in a therapeutically effective amount as a plurality of particles;

(b) a viscosity inducing component in an amount effective to increase the viscosity of the composition, and;

(c) an aqueous carrier component,

wherein the composition has a viscosity of at least about 10 cps at a shear rate of 0.1/second and is injectable into the vitreous of a human eye, and wherein the posterior ocular condition is treated for up to about 30 weeks by the triamcinolone released from the implant.

31. The method of claim 30, wherein:

(a) the pharmaceutical composition comprises triamcinolone particles, polymeric hyaluronate, in which the triamcinolone particles are suspended, sodium chloride, sodium phosphate, and water;

(b) the intravitreal administration is by injection through a 27 gauge needle into the vitreous of a human eye, and;

(c) in an aggregate number of patients practise of the method results in less intraocular inflammation that does practise of the same method with a second pharmaceutical composition which is a saline solution or suspension of a triamcinolone.

32. A process for making a pharmaceutical composition, the process comprising the steps of:

(a) mixing triamcinolone particles about 4 microns to about 8 microns in diameter with sodium chloride;

(b) heating the triamcinolone and sodium chloride mixture to a temperature between about 120°

C. and about 140°

C., thereby preparing a first part;

(c) mixing a sodium phosphate and water, thereby preparing a second part;

(d) dissolving sodium hyaluronate with a molecular weight between about 1.0 million Daltons and about 1.9 million Daltons in water;

(e) lyophilization of the dissolved sodium hyaluronate;

(f) reconstitution of the lyophilized sodium hyaluronate, thereby preparing a third part, and;

(g) combining the first, second and third parts, thereby making a sterile, uniform triamcinolone pharmaceutical composition which is, an opaque white gel suspension suitable for intravitreal injection to treat an ocular condition.

36. A pharmaceutical composition for treating a posterior ocular condition, comprising:

(a) triamcinolone particles;

(b) polymeric hyaluronate, in which the triamcinolone particles are suspended;

(c) sodium chloride;

(d) sodium phosphate, and;

(e) water,

wherein the pharmaceutical composition has a viscosity at a shear rate of about 0.1/second of between about 80,000 cps and about 300,000 cps.

37. A pharmaceutical composition for treating a posterior ocular condition, comprising:

(a) triamcinolone particles;

(b) polymeric hyaluronate, in which the triamcinolone particles are suspended;

(c) sodium chloride;

(d) sodium phosphate, and;

(e) water, wherein the pharmaceutical composition has a viscosity at a shear rate of about 0.1/second of between about 100,000 cps and about 150,000 cps, and wherein the composition is injected into the vitreous through a 30 gauge needle.