Novel methods of treatment and deliver modes

• US 20050106128A1
• Filed: 11/01/2002
• Published: 05/19/2005
• Est. Priority Date: 11/07/2001
• Status: Abandoned Application

• Current Assignee: Living Cell Products Pty., Limited
• Original Assignee: Living Cell Products Pty., Limited
• Inventors: Elliott, Robert Bartlett, Skinner, Stephen John Martin
• Application Number:
  US10/494,820
• Publication Number:
  US 20050106128A1
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/42 Respiratory system, e.g. lungs, bronchi or lung cells
• CPC Class Codes: A61K 38/4886 Metalloendopeptidases (3.4.24), e.g. collagenase
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• 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 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: C12Y 304/24017 Stromelysin 1 (3.4.24.17)

Abstract

The invention relates to a novel method of administration, and device employed in the method, for administering a treatment species to the lungs of a recipient patient. The method involves introducing the device of the invention to the venous system of the patient, the size of the treatment species being such that, upon introduction to the venous system of the patient, the device will impact in a region of a lung capillary of the patient. The treatment species gains access to the lung and/or lung epithelia due to proteases associated with the treatments species. The application of the method to the treatment of cystic fibrosis is also claimed.

Claims

1. A biological device capable, upon impaction in a lung capillary of a patient suffering from cystic fibrosis, of treating the patient comprising or including:

i) one or more cells exhibiting substantially normal CFTR production;

ii) one or more coatings of a suitable biocompatible material around the one of more cells;

iii) one or more proteases associated with the one or more coatings;

wherein the size of the biological device is such that, upon introduction to the venous system of the patient the device will impact substantially in the region of a lung capillary of the patient, and wherein, upon impaction, by disruption of the outer surface of the device or otherwise, the one or more proteases are able to act upon a wall of the lung capillary, thereby allowing access (directly or indirectly) of the one or more cells to the lung epithelia.

2. A device as claimed in claim 1 wherein the diameter of the biological device is substantially within the range 20-80 micrometers.

3. A device as claimed in claim 2 wherein the one or more proteases are distributed substantially uniformly in the one or more coatings, whether it is uniformly through all of the one or more coatings or uniformly within one or more of the one or more coatings.

4. A device as claimed in claim 2 wherein the one or more proteases are distributed throughout the one or more coatings in clusters.

5. A device as claimed in claim 3 or 4 wherein the one or more proteases have the characteristics of proteases secreted by the Ascaris roundworm.

6. A device as claimed in claim 5 wherein the one or more proteases are neutral proteinases.

7. A device as claimed in claim 6 wherein the one or more proteases are collagenases or proteo glycanases.

8. A device as claimed in claim 7 wherein the cells may include human lung cells and/or porcine lung cells and/or human lung stem cells.

9. A device as claimed in claim 8 wherein the one or more coatings around the cells provide(s) a protective coating to the cells and is/are permeable to nutrients, including one or more of water, salts and glucose.

10. A device as claimed in claim 9 wherein the one or more coatings is/are or include alginate.

11. A device as claimed in claim 10 wherein the one or more coatings comprise the following:

i) an inner layer of alginate,

ii) polyornithine,

iii) an outer layer of alginate.

12. A device as claimed in claim 11 wherein the proteases are in clusters, contained within a microcapsule, and are held in or on the outer layer of alginate.

13. A device as claimed in claim 12 wherein the microcapsule is of a suitable water absorbing material.

14. A device as claimed in claim 13 wherein the suitable water absorbing material is gelatin.

15. A device as claimed in claim 14 wherein the one or more cells have been obtained according to a process of isolation from a donor.

16. A device as claimed in claim 15 wherein the process of isolation includes exposure of the one or more cells to a liquid medium containing one or more of:

1. Nicotinamide,

2. Liberase/Collagenase,

3. Lignocaine.

17. A device as claimed in claim 16 wherein the biological device is contained within or supported by a pharmaceutically acceptable intravenous carrier.

36. An intravenous preparation for administration to a patient suffering from cystic fibrosis comprising or including:

(a) a biological device as claimed in claim 1, and

(b) a pharmaceutically acceptable intravenous carrier.

37. A preparation as claimed in claim 36 wherein the intravenous preparation may be stored at a range of temperatures not less that 2 C. and not exceeding 30 C. without destabilisation and/or decomposition.

18. A method of preparing a biological device capable, upon impaction in a lung capillary of a patient suffering from cystic fibrosis, of treating the patient comprising or including the steps of:

i) isolation of one or more cells exhibiting substantially normal CFTR production;

ii) a step of coating the one or more cells with one or more coatings of a suitable biocompatible material;

iii) attaching or otherwise associating one or more proteases with the one or more coatings;

wherein the size of the biological device is such that, upon introduction to the venous system of the patient the device will impact substantially in the region of a lung capillary of the patient.

19. A method as claimed in claim 18 wherein the diameter of the biological device is substantially in the range 20-80 micrometers.

20. A method as claimed in claim 19 wherein the one or more cells are human lung cells and/or porcine lung cells and/or human lung stem cells.

21. A method as claimed in claim 20 wherein nicotinamide and/or Lignocaine is/are introduced to the one or more cells prior to coating, or at any one or more stages of the procedure.

22. A method as claimed in claim 21 wherein the coating step includes the following substeps:

(a) encapsulation or encasement of the one or more cells in a suitable biocompatible material,

(b) coating the encapsulated one or more cells with a positively charged material,

(c) providing an outer coat of a suitable biocompatible material.

23. A method as claimed in claim 22 wherein the biocompatible material employed in (a) and (c) is a suitable alginate.

24. A method as claimed in claim 23 wherein the encapsulation provides a surround which prevents, once implanted, direct tissue contact with the one or more cells.

25. A method as claimed in claim 24 wherein each encapsulation involves presenting the one or more cells and a suitable alginate solution into a source of compatible cations thereby to entrap the one or more cells in a cation-alginate gel.

26. A method as claimed in claim 25 wherein the cation alginate gel is calcium-alginate gel, the alginate used in the solution is sodium alginate, and the islet and sodium alginate solution is presented as a droplet into a bath of suitable cations.

27. A method as claimed in claim 26 wherein the second layer of the capsule will be of a positively charged polymer material.

28. A method as claimed in claim 27 wherein the positively charged polymer material is poly-L-ornithine.

29. A method as claimed in claim 28 wherein the coatings comprise the following:

i) an inner layer of alginate,

ii) polyornithine,

iii) an outer layer of alginate.

30. A method as claimed in claim 29 wherein step iii) includes substantially uniform distribution of the one or more proteases in the one or more coatings (by mixing with the outer coating before application for example).

31. A method as claimed in claim 29 wherein step iii) includes distributing the one or more proteases throughout the outer coating in clusters (by mixing the clusters with the outer coating before application for example).

32. A method as claimed in claim 30 or 31 wherein the one or more proteases have the characteristics of proteases secreted by migrating parasitic nematodes.

33. A method as claimed in claim 32 wherein the nematodes are Ascaris suum, or stercoralis.

34. A method as claimed in claim 33 wherein the one or more proteases are neutral proteinases.

35. A method as claimed in claim 34 wherein the one or more proteases may be collagenases or proteoglycanases.

38. A method of treating a patient suffering from cystic fibrosis comprising or including the step of:

Intravenous administration to the patient of an intravenous preparation comprising

or including;

(a) a pharmaceutically acceptable intravenous carrier, and

(b) a biological device, wherein the biological device is capable, upon impaction in a lung capillary of a patient suffering from cystic fibrosis, of treating the patient.

39. A method as claimed in claim 38 wherein the biological device comprises or includes:

i) one or more cells exhibiting substantially normal CFTR production;

ii) one or more coatings of a suitable biocompatible material around the one of more cells;

iii) one or more proteases associated with the one or more coatings;

 

and wherein the size of the biological device is such that, upon introduction to the venous system of the patient the device will impact substantially in the region of a lung capillary of the patient, and wherein, upon impaction, by disruption of the outer surface of the device or otherwise, the one or more proteases are able to act upon a wall of the lung capillary, thereby allowing access (directly or indirectly) of the one or more cells to the lung epithelia.

40. A method as claimed in claim 39 wherein the diameter of the biological device is substantially within the range 20-80 micrometers.

41. A method as claimed in claim 40 wherein the one or more proteases are distributed substantially uniformly in the one or more coatings, whether it is uniformly though all of the one or more coatings or uniformly within one or more of the one or more coatings.

42. A method as claimed in claim 40 wherein the one or more proteases are distributed throughout the one or more coatings in clusters.

43. A method as claimed in claim 41 or 42 wherein the one or more proteases have the characteristics of proteases secreted by migrating parasitic nematodes.

44. A method as claimed in claim 43 wherein the nematodes are Ascaris suum, or stercoralis.

45. A method as claimed in claim 44 wherein the one or more proteases are neutral proteinases.

46. A method as claimed in claim 45 wherein the one or more proteases may be collagenases or proteo glycanases.

47. A method as claimed in claim 46 wherein the cells may include human lung cells and/or porcine lung cells and/or human lung stem cells.

48. A method as claimed in claim 47 wherein the one or more coatings around the cells provide a protective coating to the cells and are permeable to nutrients, including one or more of water, salts, glucose and amino acids.

49. A method as claimed in claim 48 wherein the one or more coatings are, or include alginate.

50. A method as claimed in claim 49 wherein the coatings comprise the following:

i) an inner layer of alginate,

ii) polyornithine,

iii) an outer layer of alginate.

51. A method as claimed in claim 50 wherein the proteases are in clusters, contained within a microcapsule, and are held in or on the outer layer of alginate.

52. A method as claimed in claim 51 wherein the microcapsule gelatin.

53. A method as claimed in claim 52 wherein the one or more cells have been obtained according to a process of isolation from a donor.

54. A method as claimed in claim 53 wherein the process of isolation includes exposure of the one or more cells to a medium containing one or more of:

Nicotinamide,

Liberase/Collagenase,

Lignocaine.

55. A method as claimed in claim 54 wherein the patient prior to and/or during and/or after administration of the intravenous preparation is treated with an oral dose of nicotinamide.

56. A biological device capable upon impaction in a lung capillary of a patient suffering from a condition or illness (“

the condition”

) of the lung or lung region, of treating the condition, comprising or including;

iii) one or more treatment species capable of treating the condition,

iv) One or more proteases associated with the one ore more treatment species,

 

wherein the size of the treatment species is such that, upon introduction to the venous system of the patient, the device will impact substantially in a region of a lung capillary of the patient, and wherein, upon impaction by disruption of the outer surface of the device or otherwise, the one or more proteases are able to act upon a wall of the lung capillary, thereby allowing access (directly or indirectly) of the one or more treatment species to the lung epithelia.

57. A biological device as claimed in claim 56 wherein the device includes one ore more external coatings of a biocompatible material around the one or more treatment species, the one or more proteases being distributed within the one ore more external coatings, and the diameter of the device is substantially within the range 20-80 micrometers.

58. A device as claimed in claim 57 wherein the one or more proteases have the characteristics of proteases secreted by the Ascaris roundworm, and are neutral proteinases.

61. An intravenous preparation for administration to a patient suffering from a condition or illness of the lung or lung region comprising or including:

(c) a biological device as claimed in any one of claims 56 to 58, and

(d) a pharmaceutically acceptable intravenous carrier.

64. A method as claimed in claim 63 wherein the biological device is as claimed in any one of claims 56 to 58.

59. A method of preparing a biological device capable, upon impaction in a lung capillary of a patient suffering from a condition or illness (“

the condition”

) of the lung or lung region of treating the condition comprising or including the steps of;

i) isolation of one or more treatment species capable of treating the condition;

a step of coating the one or more cells with one or more coatings of a suitable biocompatible material;

ii) attaching or otherwise associating one or more proteases with the one or more coatings;

 

wherein the size of the biological device is such that, upon introduction to the venous system of the patient the device will impact substantially in the region of a lung capillary of the patient.

60. A method as claimed in claim 59 wherein the diameter of the biological device is substantially in the range 20-80 micrometers.

62. A method of treating a patient suffering from a condition or illness (“

the condition”

) of the lung or lung region comprising or including the step of;

Intravenous administration to the patient of an intravenous preparation comprising or including;

(c) a pharmaceutically acceptable intravenous carrier, and

(d) a biological device,

 

wherein the biological device is capable, upon impaction in a lung capillary of a patient suffering from the condition, of treating the patient.

63. A method as claimed in claim 62 wherein the diameter of the biological device is substantially within the range 20-80 micrometers.