NOVEL BIOMATERIALS AND A METHOD FOR MAKING AND USING SAME

• US 20080207561A1
• Filed: 01/31/2008
• Published: 08/28/2008
• Est. Priority Date: 01/31/2007
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Chang, James N., Kloster, Kaia L., Utecht, Ronald E., Haberer, Barbara R., Downey, Therese M., Youso, Patrick D.
• Granted Patent: US 8,252,771 B2
• Time in Patent Office: Days
• US Class Current: 514/55
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• 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 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 27/20 Polysaccharides
• 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: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

A novel biomaterial is disclosed having unique properties that make it useful in ocular drug delivery applications, where the drugs selected from the group consisting of a prostaglandin, a prostamide, a non-steroidal anti-inflammatory drug (NSAID), and a corticosteroid, and mixtures, derivatives, salts and esters thereof.

Claims

1. A pharmaceutical composition for treating an ocular disease or condition, the composition comprising:

a chitosan composition comprising a treated chitosan, a modified chitosan, a modified and treated chitosan, or a mixture thereof, where each chitosan exhibit changes in chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan, and

a therapeutic agent selected from the group consisting of a prostaglandin, a prostamide and a mixture thereof, a non-steroidal anti-inflammatory drug (NSAID) and a mixture of NSAIDs, and a corticosteroid and a mixture of corticosteroids,

where the chitosan composition is adapted to release a therapeutically effective amount of the therapeutical agent over a period of time.

2. The composition of claim 1, further comprising a preservative.

3. The composition of claim 2, wherein the preservative is selected from the group consisting of benzalkonium chloride, chlorhexidine, PHMB (polyhexamethylene biguanide), methyl and ethyl parabens, hexetidine, chlorite components, other ophthalmically acceptable preservatives and mixtures thereof in a concentration range of about 0.00001% to about 0.05% or about 0.1% (w/v) of the composition.

4. The composition of claim 1, further comprising an excipient.

5. The composition of claim 4, wherein the excipient an ophthalmically compatible excipient.

6. The composition of claim 1, further comprising a buffer.

7. The composition of claim 6, wherein the buffer is selected from the group consisting of acetate buffers, citrate buffers, phosphate buffers, borate buffers and mixtures thereof.

8. The composition of claim 1, further comprising a vehicle.

9. The composition of claim 8, wherein the vehicle is an ophthalmically compatible vehicle.

10. The composition of claim 1, wherein the therapeutic agent is covalently bonded to sites on the chitosan.

11. The composition of claim 1, wherein the therapeutic agent is covalently bonded to sites on the chitosan via a linker.

12. A process for making a pharmaceutical composition for treating an ocular condition comprising:

contacting a chitosan composition comprising a treated chitosan, a modified chitosan, a modified and treated chitosan, or a mixture thereof and a therapeutically effective amount of a pharmaceutical agent to form a substantially uniform composition,

where each chitosan exhibits changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan, and

where each modified chitosan is prepared by forming covalent linkages between the chitosan and one functional group or a plurality of functional groups, by forming non-covalent associations between the chitosan and one atomic or molecular agent or a plurality of atomic and/or molecular agents, or by forming mixtures between the chitosan and one atomic or molecular agent or a plurality of atomic and/or molecular agents altering the chitosan through covalent attachments of one functional group or a plurality of functional groups, non-covalent associations with one atomic or molecular agent or a plurality of atomic and/or molecular agents, and/or coadditions of one atomic or molecular agent or a plurality of atomic and/or molecular agents and

where the pharmaceutical agent is selected from the group consisting of a prostaglandin, a prostamide and a mixture thereof, a non-steroidal anti-inflammatory drug (NSAID) and a mixture of NSAIDs, and a corticosteroid and a mixture of corticosteroids.

13. The process of claim 12, further comprising a preservative.

14. The process of claim 13, wherein the preservative is selected from the group consisting of benzalkonium chloride, chlorhexidine, PHMB (polyhexamethylene biguanide), methyl and ethyl parabens, hexetidine, chlorite components, other ophthalmically acceptable preservatives and mixtures thereof in a concentration range of about 0.00001% to about 0.05% or about 0.1% (w/v) of the composition.

15. The process of claim 12, further comprising an excipient.

16. The process of claim 15, wherein the excipient is an ophthalmically compatible excipient.

17. The process of claim 12, further comprising a buffer.

18. The process of claim 17, wherein the buffer is selected from the group consisting of acetate buffers, citrate buffers, phosphate buffers, borate buffers and mixtures thereof.

19. The process of claim 12, further comprising a vehicle.

20. The process of claim 19, wherein the vehicle is an ophthalmically compatible vehicle.

21. The process of claim 12, wherein the therapeutic agent is covalently bonded to sites on the chitosan.

22. The process of claim 12, wherein the therapeutic agent is covalently bonded to sites on the chitosan via a linker.

23. A pharmaceutical composition made by the process of claim 12.

24. A process for making a pharmaceutical composition for treating an ocular condition comprising:

contacting a chitosan composition comprising a treated chitosan, a modified chitosan, a modified and treated chitosan, or a mixture thereof and a therapeutically effective amount of pharmaceutical agent under conditions to covalently bond the agent to sites on the chitosan,

where each chitosan exhibits changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan, and

where each modified chitosan is prepared by forming covalent linkages between the chitosan and one functional group or a plurality of functional groups, by forming non-covalent associations between the chitosan and one atomic or molecular agent or a plurality of atomic and/or molecular agents, or by forming mixtures between the chitosan and one atomic or molecular agent or a plurality of atomic and/or molecular agents altering the chitosan through covalent attachments of one functional group or a plurality of functional groups, non-covalent associations with one atomic or molecular agent or a plurality of atomic and/or molecular agents, and/or coadditions of one atomic or molecular agent or a plurality of atomic and/or molecular agents and

where the pharmaceutical agent is selected from the group consisting of a prostaglandin, a prostamide and a mixture thereof, a non-steroidal anti-inflammatory drug (NSAID) and a mixture of NSAIDs, and a corticosteroid and a mixture of corticosteroids.

25. The process of claim 24, further comprising a preservative.

26. The process of claim 25, wherein the preservative is selected from the group consisting of benzalkonium chloride, chlorhexidine, PHMB (polyhexamethylene biguanide), methyl and ethyl parabens, hexetidine, chlorite components, other ophthalmically acceptable preservatives and mixtures thereof in a concentration range of about 0.00001% to about 0.05% or about 0.1% (w/v) of the composition.

27. The process of claim 24, further comprising an excipient.

28. The process of claim 27, wherein the excipient is an ophthalmically compatible excipient.

29. The process of claim 24, further comprising a buffer.

30. The process of claim 29, wherein the buffer is selected from the group consisting of acetate buffers, citrate buffers, phosphate buffers, borate buffers and mixtures thereof.

31. The process of claim 24, further comprising a vehicle.

32. The process of claim 31, wherein the vehicle is an ophthalmically compatible vehicle.

33. The process of claim 24, wherein the therapeutic agent is covalently bonded to sites on the chitosan.

34. The process of claim 24, wherein the therapeutic agent is covalently bonded to sites on the chitosan via a linker.

35. A pharmaceutical composition made by the process of claim 24.

36. A method for treating an ocular disease or condition, the method comprising the following steps:

administering to a patient a pharmaceutical composition comprising a chitosan composition comprising a treated chitosan, a modified chitosan, a modified and treated chitosan, or a mixture thereof and a pharmaceutical agent selected from the group consisting of a prostaglandin, a prostamide and a mixture thereof, a non-steroidal anti-inflammatory drug (NSAID) and a mixture of NSAIDs, and a corticosteroid and a mixture of corticosteroids,

where each chitosan exhibits changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan,

where each modified chitosan is prepared by forming covalent linkages between the chitosan and one functional group or a plurality of functional groups, by forming non-covalent associations between the chitosan and one atomic or molecular agent or a plurality of atomic and/or molecular agents, or by forming mixtures between the chitosan and one atomic or molecular agent or a plurality of atomic and/or molecular agents altering the chitosan through covalent attachments of one functional group or a plurality of functional groups, non-covalent associations with one atomic or molecular agent or a plurality of atomic and/or molecular agents, and/or coadditions of one atomic or molecular agent or a plurality of atomic and/or molecular agents and

where the pharmaceutical composition is adapted to release a therapeutically effective amount of the pharmaceutical agent over a period of time and where the therapeutically effective amount is adapted to treat or cure an ocular disease or condition or ameliorate symptoms of an ocular disease or condition.

37. An ocular drug delivery composition comprising a chitosan matrix and a pharmaceutically effective amount of an ocular drug, where the ocular drug is selected from the group consisting of a prostaglandin, a prostamide or a mixture thereof, or a non-steroidal anti-inflammatory drug (NSAID) or a mixture of NSAIDs or a corticosteroid or a mixture of corticosteroids, where the chitosan matrix comprises a treated chitosan, a modified chitosan, a treated and modified chitosan, or a mixture thereof, where each chitosan exhibits changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan, and where the composition is adapted to release a therapeutically effective amount of the ocular drug over a period of time.

38. The composition of claim 37, wherein the period of time for a composition including a prostaglandin, a prostamide or a mixture thereof is between a day and about 1 year.

39. The composition of claim 37, wherein the period of time for a composition including a prostaglandin, a prostamide or a mixture thereof is between about a month and about six months.

40. The composition of claim 37, wherein the period of time for a composition including a prostaglandin, a prostamide or a mixture thereof is between about a month and about four months.

41. The composition of claim 37, wherein the period of time for a composition including a prostaglandin, a prostamide or a mixture thereof is at least three months.

42. The composition of claim 37, wherein the period of time for a composition including a prostaglandin, a prostamide or a mixture thereof is at least two months.

43. The composition of claim 37, wherein the period of time for a composition including a prostaglandin, a prostamide or a mixture thereof is at least one month.

44. The composition of claim 37, wherein the period of time for a composition including a non-steroidal anti-inflammatory drug (NSAID) or a mixture of NSAIDs or a corticosteroid or a mixture of corticosteroids is between about 0.5 hours and about 36 hours.

45. The composition of claim 37, wherein the period of time for a composition including a non-steroidal anti-inflammatory drug (NSAID) or a mixture of NSAIDs or a corticosteroid or a mixture of corticosteroids is between about 1 hour and about 36 hours.

46. The composition of claim 37, wherein the period of time for a composition including a non-steroidal anti-inflammatory drug (NSAID) or a mixture of NSAIDs or a corticosteroid or a mixture of corticosteroids is at least 16 hours.

47. The composition of claim 37, wherein the period of time for a composition including a non-steroidal anti-inflammatory drug (NSAID) or a mixture of NSAIDs or a corticosteroid or a mixture of corticosteroids is at least 8 hours.

48. The composition of claim 37, wherein the period of time for a composition including a non-steroidal anti-inflammatory drug (NSAID) or a mixture of NSAIDs or a corticosteroid or a mixture of corticosteroids is at least 4 hours.

49. A method for administering an ocular drug delivery composition comprising:

administering an effective amount of the composition via injection to an eye, or tissue surrounding the eye, of an animal including a human,

where the composition comprises;

a treated chitosan, a modified chitosan, a treated and modified chitosan, or a mixture thereof, where each chitosan exhibits changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan and

a prostaglandin, a prostamide or a mixture thereof.

50. A method for administering an ocular drug delivery composition comprising:

administering an effective amount of the composition topically to an eye of an animal including a human,

where the composition comprises;

a treated chitosan, a modified chitosan, a treated and modified chitosan, or a mixture thereof, where each chitosan exhibits changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan and

and a non-steroidal anti-inflammatory drug (NSAID) or a mixture of NSAIDs or a corticosteroid or a mixture of corticosteroids.

51. A pharmaceutical composition for treating an ocular disease or condition, the composition comprising:

a treated chitosan, a modified chitosan, a treated and modified chitosan, or a mixture thereof, and;

a therapeutic agent selected from the group consisting of a prostaglandin, a prostamide, a non-steroidal anti-inflammatory drug (NSAID), and a corticosteroid, and mixtures, derivatives, salts and esters thereof.

52. A process for making a pharmaceutical composition for treating an ocular condition, the process comprising the steps of:

contacting a modified chitosan and a therapeutic agent, wherein the therapeutic agent is selected from the group consisting of a prostaglandin, a prostamide, a non-steroidal anti-inflammatory drug (NSAID), and a corticosteroid, and mixtures, derivatives, salts and esters thereof.

53. A method for treating an ocular disease or condition, the method comprising the step of:

administering to an eye of a patient a pharmaceutical composition comprising a treated chitosan, a modified chitosan, a treated and modified chitosan, or a mixture thereof, and a therapeutic agent selected from the group consisting of a prostaglandin, a prostamide, a non-steroidal anti-inflammatory drug (NSAID), and a corticosteroid, and mixtures, derivatives, salts and esters thereof, thereby treating the ocular disease or condition.

54. An ocular drug delivery composition comprising a chitosan matrix and a pharmaceutically effective amount of an ocular drug,

where the ocular drug is selected from the group consisting of a non-steroidal anti-inflammatory drug (NSAID) or a mixture of an NSAID or a corticosteroid or a mixture of corticosteroids,

where the chitosan matrix comprises a treated chitosan, a modified chitosan, a modified and treated chitosan, or a mixture thereof, where each chitosan exhibits changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan, and

where each treated chitosan is prepared by dialyzing a solubilized chitosan against water, a salt solution and/or an anionic solution,

where each modified chitosan is prepared by forming covalent linkages between the chitosan and one functional group or a plurality of functional groups, by forming non-covalent associations between the chitosan and one atomic or molecular agent or a plurality of atomic and/or molecular agents, or by forming mixtures between the chitosan and one atomic or molecular agent or a plurality of atomic and/or molecular agents altering the chitosan through covalent attachments of one functional group or a plurality of functional groups, non-covalent associations with one atomic or molecular agent or a plurality of atomic and/or molecular agents, and/or coadditions of one atomic or molecular agent or a plurality of atomic and/or molecular agents and

where the composition increases a tissue drug concentration compared to a composition in the absence of the chitosan matrix affording a lower pharmaceutically effective amount of the drug compared to the composition in the absence of the chitosan matrix.

55. The composition of claim 54, wherein the lower pharmaceutically effective amount is at least 10% less than an amount of the drug in a comparable composition in the absence of the chitosan matrix.

56. The composition of claim 54, wherein the lower pharmaceutically effective amount is at least 20% less than an amount of the drug in a comparable composition in the absence of the chitosan matrix.

57. The composition of claim 54, wherein the lower pharmaceutically effective amount is at least 30% less than an amount of the drug in a comparable composition in the absence of the chitosan matrix.

58. The composition of claim 54, wherein the lower pharmaceutically effective amount is at least 40% less than an amount of the drug in a comparable composition in the absence of the chitosan matrix.

59. The composition of claim 54, wherein the lower pharmaceutically effective amount is at least 50% less than an amount of the drug in a comparable composition in the absence of the chitosan matrix.