Processing

Please wait...

Settings

Settings

Goto Application

1. WO2020110100 - DEVICES FOR TOPICAL DELIVERY OF ACTIVE AGENTS TO A TARGET SITE

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

CLAIMS:

1. A flexible device for topical delivery of at least one active agent to a target site, the device comprises a flexible substrate for placing onto a skin portion and having a plurality of spaced-apart cells, each cell in said plurality containing at least one active agent and having at least one wall portion made of a film of at least one polymeric material that is at least partially disintegrable upon contact with an aqueous fluid to thereby release the active agent to the target site.

2. The device of claim 1, wherein said aqueous fluid is perspiration.

3. The device of claim 1, wherein said aqueous fluid is exudate.

4. The device of claim 1, wherein said aqueous fluid is lacrimal fluid.

5. The device of claim 1, wherein aqueous fluid is a water-based fluid applied externally onto the device during and/or after application to the skin portion.

6. The device of any one of claims 1 to 5, wherein the cells in said plurality of cells are configured for selective disintegration upon contact with said aqueous fluid.

7. The device of claim 6, wherein at least one portion of cells being different in at least one property from at least another portion of cells in said plurality of cells.

8. The device of claim 7, wherein said property being at least one property selected from film thickness, molecular weight of the polymeric material, composition of the polymeric material, film texture, water solubility of the film, volume of cell, geometry of cell, size of disintegrable wall portion, and type of active agent contained therein.

9. The device of any one of claims 1 to 8, wherein said polymeric material is selected from polysaccharide, polyethyleneoxide (PEO), polyvinyl-pyrrolidone (PVP), polyvinyl-alcohol (PVA), polyacrylic acid (PAA), polyacryloamides, polyoxazoline, cellulose ethers (e.g. HPMC, HPC).

10. The device of claim 9, wherein said polymeric material is PVA.

11. The device of claim 9 or 10, wherein said polymeric material has a molecular weight of at least about 50,000 g/mole.

12. The device of claim 11, wherein said polymeric material has a molecular weight of between about 10,000 and about 200,000 g/mole.

13. The device of any one of claims 1 to 12, wherein said at least one active agent is selected from an anti-inflammatory agent, a pain-relief agent, wound healing promoting agents, an analgesic, an antihistamine, an opioid or opioid derivative, growth hormone, a cannabinoid, an antifungal agent, an antiviral agent, an antiseptic, an antimicrobial agent, an antibiotic, and a disinfectant.

14. The device of claim 13, wherein the cannabinoid is at least one cannabinoid selected from cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerovarinic acid (CBGVA), cannabigerovarin (CBGV), cannabichromenic acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), cannabichromevarin (CBCV), cannabidiolic acid (CBDA), cannabidiol (CDB), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD-C4), cannabidivarinic acid (CBDVA), cannabidiorcol (CBD-Ci), delta-9-tetrahydrocannabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9-tetrahydrocannabinol (THC), delta-9-tetrahydrocannabinolic acid-C4 (THCA-C4), delta-9-tetrahydrocannabinol-C4 (THCA-C4), delta-9-tetrahydrocannabivarinic acid (THCVA), delta-9-tetrahydrocannabivarin (THCV), delta-9-tetrahydrocannabiorcolic acid (THCA-Ci), delta-9-tetrahydrocannabiorcol (THC-Ci), delta-7-cis-iso-tetrahydrocannabivarin, delta-8-tetrahydrocannabinolic acid A (A8-THCA), delta-8-tetrahydrocannabinol (A8-THC), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabivarin (CBV), cannabinol-C2 (CBN-C2), cannabiorcol (CBN-Ci), cannabinodiol (CBND), cannabinodivarin (CBVD), cannabitriol (CBT), 10-ethoxy-9-hydroxy-delta-6a-tetrahydrocannabinol, 8,9-dihydroxy-delta-6a-tetrahydrocannabinol, cannabitriolvarin (CBTV), ethoxy-cannabitriolvarin (CBTVE), dehydrocannabifuran (DCBF), cannabifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), delta-9-cis-tetrahydrocannabinol (cis-THC), 3,4,5,6-tetrahtdro-7-hydroxy-a-a-2-trimethyl-9-n-propyl-2,6-methano-2H- l-benzoxocin-5-methanol (OH-iso-HHCV), cannabiripsol (CBR), trihydroxy-delta-9-tetrahydroxycannabinol (triOH-THC), and any other cannabinoid.

15. The device of claim 14, wherein the cannabinoid is selected from CBD, CBDA, THC, and mixtures thereof.

16. The device of any one of claims 1 to 15, wherein all of the cells in said plurality of cells contain the same active agent.

17. The device of claim 16, wherein the cells differ in their disintegration rate, such that the difference in the integration rate forms a sequence of disintegration of the cells with a defined time interval between disintegration of subsequent cells in said sequence, the time interval being defined by the difference in disintegration rate.

18. The device of claim 17, wherein each cell comprises said active agent in a therapeutically effective dose.

19. The device of any one of claims 1 to 15, wherein at least one portion of the cells containing an active agent differing from the active agent contained in at least another portion of cells in said plurality of cells.

20. The device of any one of claims 1 to 19, wherein said at least one portion of cells and at least another portion of cells being configured to have different disintegration rates to release said active agents therefrom at different rates.

21. The device of any one of claims 1 to 20, wherein said polymeric material is fully disintegrable within between about 5 second and 30 minutes from contact with said perspiration or exudate.

22. The device of claim 21, wherein said polymeric material is fully disintegrable within between about 5 second and 10 minutes from contact with said aqueous fluid.

23. The device of claim 22, wherein said polymeric material is fully disintegrable within between about 5 second and 2 minutes from contact with said aqueous fluid.

24. The device of any one of claims 1 to 23, wherein at least a portion of cells further contain a decomposable agent capable of forming a gaseous decomposition product upon contact with said aqueous fluid.

25. The device of claim 24, wherein said decomposable material is calcium bicarbonate.

26. The device of any one of claims 1 to 25, wherein said flexible substrate being made of a material substantially non-disintegrable upon contact with aqueous fluid.

27. The device of any one of claims 1 to 26, wherein the cells are spaced apart by substantially non-disintegrable segments.

28. The device of claim 27, wherein said segments being non-uniform in thickness and/or density to permit flexibility and/or foldability of said segments.

29. The device of any one of claims 1 to 28, being a bandage, a dressing, or a sleeve.

30. The device of claim 29, further comprising an adhesive on at least a portion of the device's perimeter.

31. The device of claim 30, being a plaster or adhesive bandage.

32. The device of any one of claims 1 to 28, being configured for insertion into a body cavity or lumen.

33. The device of any one of claims 1 to 32, wherein said at least one active agent is formulated into a pharmaceutical composition comprising said active agent and at least one pharmaceutically acceptable excipient or carrier.

34. The device of claim 33, wherein said pharmaceutical composition is in a form selected from a gel, a cream, an oil, an ointment, a non-aqueous liquid, a non-aqueous solution, an emulsion, a microemulsion, a powder, a flake, a granule, a microparticle, a microcapsule, a nanoparticle, a nanocapsule, or a liposome.

35. A method of manufacturing a flexible device for topical delivery of at least one active agent to a target site, the method comprising:

- forming a plurality of spaced-apart cells each cell having at least one wall portion made of a film of at least one polymeric material that is at least partially disintegrable upon contact with an aqueous fluid;

- filling said cells with said at least one active material; and

- sealing the cells with a flexible substrate to form the device.

36. The method of claim 35, for producing the device of any one of claims 1 to 34.

37. A method of manufacturing a device of any one of claims 1 to 34, the method comprising:

(a) bringing a flexible substrate and a film of at least one aqueous fluid-disintegrable polymeric material in proximity one to the other;

(b) integrating said flexible substrate with said film to form a plurality of spaced-apart pre-cells, the pre-cells having a portion of their perimeter non-integrated,

(c) introducing at least one active agent into said pre-cells through the non-integrated portion, and

(d) sealing said pre-cells by integrating said flexible substrate with said film along said portion to thereby form said spaced-apart cells.

38. The method of claim 37, wherein steps (a) to (d) are repeated to manufacture a device comprising an array of spaced-apart cells.

39. The method of claim 37 or 38, wherein said integrating is carried out by welding, heat sealing, contact welding, high frequency welding, ultrasonic welding, laser welding, solvent welding.

40. The method of any one of claims 37 to 39, wherein said integrating forms a plurality of cells that are spaced apart by substantially non-disintegrable segments.

41. The method of claim 40, wherein said segments being non-uniform in thickness and/or density to permit flexibility and/or foldability of said segments after integration.

42. The method of any one of claims 37 to 41, wherein said film having cell-forming sections and seal-forming sections, such that integrating is carried out by welding said film to said substrate along said seal-forming sections.

43. The method of claim 42, wherein said cell-forming sections are formed from a disintegrable polymeric material.

44. The method of claim 42 or 43, wherein said seal-forming sections comprise or formed of a non-disintegrable polymeric material.

45. The method of claim 42 or 43, wherein said seal-forming sections comprise a laminate of polymeric layers having different disintegration properties.

46. The method of any one of claims 37 to 45, wherein the cells are spaced apart by substantially non-disintegrable segments constituted by integrated seal-forming sections.

47. The method of claim 46, wherein said segments being non-uniform in thickness and/or density to permit flexibility and/or foldability of said segments after integration.

48. The method of any one of claims 37 to 47, further comprising a step prior to (a) of texturing said film or cell-forming sections of said film.

49. The method of claim 48, wherein said texturing is carried out by embossing.

50. The method of any one of claims 37 to 49, further comprising associating the device with at least one fabric layer.

51. The method of claim 50, wherein said fabric layer is an elastic fabric layer.

52. A method of topically delivering at least one active agent to a target site, comprising contacting a flexible device of any one of claims 1 to 34 with a skin portion of a patient, such that at least a portion of the plurality of cells comes into contact with an aqueous fluid to cause selective disintegration of cells for topically releasing said active agent to said target site.

53. The method of claim 52, wherein contacting with said aqueous fluid (i) a portion of said cells to disintegrate and release a first active agent to the target site, followed by (ii) disintegration of another portion of cells for releasing a second active agent to the target site.

54. A method of treating a skin infection, comprising contacting a flexible device of any one of claims 1 to 34 with infected skin portion of a patient, at least a portion of cells in the device comprise at least one active agent for treating said skin infection, said cells being selectively disintegrable upon contact an aqueous fluid to release said active agent to said infected skin portion.

55. A method of treating a skin bum, comprising contacting a flexible device of any one of claims 1 to 34 with said skin burn, at least a portion of cells in the device comprise at least one active agent, said cells being selectively disintegrable upon contact with an aqueous fluid to release said active agent to said skin burn.

56. A method of topically delivering an anti-inflammatory agent to a target site, comprising contacting a flexible device of any one of claims 1 to 34 with a skin portion of a patient, at least a portion of cells in the device comprise at least anti-inflammatory agent, said cells being selectively disintegrable upon contact with an aqueous fluid to release said anti-inflammatory agent to said skin portion.

57. A method of managing pain by topical delivery of at least one active agent (e.g. an analgesic), comprising contacting a flexible device of any one of claims 1 to 34 with a skin portion of a patient, at least a portion of cells in the device comprise at least one active agent, said cells being selectively disintegrable upon contact with an aqueous fluid to release said active agent to said skin portion.

58. A method of treating a skin ulcer or a pressure ulcer, comprising contacting a flexible device of any one of claims 1 to 34 with said ulcer, at least a portion of cells in the device comprise at least one active agent, said cells being selectively disintegrable upon contact with an aqueous fluid to release said active agent to said skin ulcer.

59. The method of any one of claims 52 to 58, wherein the aqueous fluid is selected from perspiration, exudate, lacrimal fluid and externally- applied water-based fluid.

60. A method of delivering an active agent to the eye, comprising contacting a flexible device of any one of claims 1 to 34 with an eye or a skin area surrounding the eye of a patient, at least a portion of cells in the device comprise said at least one active agent, said cells being selectively disintegrable upon contact with perspiration, exudate, lacrimal fluid or an externally-applied water-based fluid to release said active agent to the eye.

61. A flexible device for topical delivery of a sequence of doses of at least one active agent to a target site, the device comprises a flexible substrate for placing onto a skin portion and having a plurality of spaced-apart cells, each cell in said plurality containing an effective dose of said at least one active agent and having at least one wall portion made of a film of at least one polymeric material that is at least partially disintegrable upon contact with an aqueous fluid to thereby release the active agent to the target site, wherein the cells differ in their disintegration rate, such that the difference in the disintegration rate forms a sequence of disintegration of the cells with a defined time interval between disintegration of subsequent cells in said sequence, the time interval being defined by the difference in disintegration rate.

62. A method of topically delivering a sequence of doses of at least one active agent to a target site, comprising contacting a flexible device of claim 61 with a skin portion of a patient, such that the plurality of cells come into contact with an aqueous fluid to cause the cells to disintegrate in a sequence of disintegration with a defined time interval between disintegration of subsequent cells in said sequence, the time interval being defined by the difference in disintegration rate, for topically releasing a sequence of doses of said active agent to said target site.

63. The method of claim 62, wherein the aqueous fluid is selected from perspiration, exudate, lacrimal fluid and externally- applied water-based fluid.