Biodegradable ocular implant

Patent metadata

Field	Value
Publication number	US-9782346-B2
Application number	US-201514862963-A
Country	US
Kind code	B2
Filing date	Sep 23, 2015
Priority date	Aug 12, 2010
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

Provided is a biodegradable ocular implant for sustained drug delivery, including a first layer comprising a first biodegradable polymer, wherein the first layer contains a drug dispersed or dissolved therein. A multi-layered biodegradable ocular implant is also disclosed.

First claim

The invention claimed is:

1. A biodegradable ocular implant for sustained drug delivery, comprising a first layer comprising a first biodegradable polymer, wherein the first layer contains a drug dispersed or dissolved therein.

2. The biodegradable ocular implant of claim 1 , further comprising at least one top layer comprising a second biodegradable polymer, wherein the at least one top layer is arranged on top of the first layer.

3. The biodegradable ocular implant of claim 2 , further comprising at least one bottom layer comprising a third biodegradable polymer, wherein the first layer is arranged on top of the at least one bottom layer to thereby form a sandwich assembly having the first layer arranged between the at least one top layer and the at least one bottom layer.

4. The biodegradable ocular implant of claim 3 , wherein the at least one top layer, or the at least one bottom layer, or both, contains a drug dispersed or dissolved in the respective layer.

5. The biodegradable ocular implant of claim 1 , wherein the drug is uniformly dissolved in the polymer matrix of the respective layer.

6. The biodegradable ocular implant of claim 1 , wherein the drug is dispersed at the surface of the respective layer.

7. The biodegradable ocular implant of claim 3 , wherein the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer are the same.

8. The biodegradable ocular implant of claim 3 , wherein the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer are different.

9. The biodegradable ocular implant of claim 1 , wherein each biodegradable polymer is independently selected from the group consisting of polylactide (PLA), poly-L-lactide (PLLA), poly-D-lactide (PDLA), poly(L-lactide-co-glycolide) (PLGA), polyethylene glycol (PEG), polypropylene glycol (PPG), polycaprolactone (PCL), polyesteramide (PEA), a PLLA copolymer, a PLGA copolymer, a PDLA copolymer, a PCL copolymer, a PEA copolymer, a PEG copolymer, a PPG copolymer, and mixtures thereof.

10. The biodegradable ocular implant of claim 9 , wherein the biodegradable polymer is a copolymer of PLA and PCL.

11. The biodegradable ocular implant of claim 10 , wherein the molar ratio PLA:PCL is between about 90:10 and about 10:90.

12. The biodegradable ocular implant of claim 11 , wherein the molar ratio PLA:PCL is 70:30.

13. The biodegradable ocular implant of claim 9 , wherein the biodegradable polymer is a triblock copolymer comprising PLA as end-blocks and a middle block selected from the group consisting of PCL, a copolymer of PCL and trimethylene carbonate (TMC), a copolymer of PCL and PLGA.

14. The biodegradable ocular implant of claim 9 , wherein the biodegradable polymer is a multiblock copolymer of polylactide-caprolactone (PLC) and PLA.

15. The biodegradable ocular implant of claim 9 , wherein the biodegradable polymer is a polyurethane type copolymer formed from di-isocyanates and butanediol, and soft segments selected from PCL/PLA and PCL/TMC.

16. The biodegradable ocular implant of claim 3 , wherein the at least one top layer or the at least one bottom layer is impermeable for the drug to provide for a directional release of the drug.

17. The biodegradable ocular implant of claim 2 , wherein each of the biodegradable polymers of the different layers has a different degradation rate.

18. The biodegradable ocular implant of claim 1 , wherein the drug comprises an ocular drug.

19. The biodegradable ocular implant of claim 1 , wherein the drug is selected from the group consisting of an immunosuppressant agent, an antibiotic, an anti-inflammatory agent, an anti-scarring agent, an anti-glaucoma medication, a prostaglandin analogue, an anti-steroidal agents, an antimicrobial agent, an anti-fibrotic antibody, and a small interfering ribonucleic acid (siRNA) molecule against fibrosis.

20. The biodegradable ocular implant of claim 19 , wherein the drug is betamethasone, prednisolone, dexmethasone, cyclosporine, latanoprost and derivates, timolol maleate, valproic acid, or ciproflaxin.

21. The biodegradable ocular implant of claim 1 , wherein each respective layer comprises 70-98 wt % (based on total weight of the layer) of the polymer matrix and 2-30 wt % of the drug.

22. The biodegradable ocular implant of claim 1 , wherein the modulus of the biodegradable ocular implant is between about 0.1 MPa and about 1,000 MPa.

23. The biodegradable ocular implant of claim 1 , wherein the elongation-to-break point of the biodegradable ocular implant is at least 300%.

24. The biodegradable ocular implant of claim 1 , further comprising an excipient or plasticizer.

25. The biodegradable ocular implant of claim 24 , wherein the excipient or plasticizer is PG, triethyl citrate (TEC) or glycerol.

26. The biodegradable ocular implant of claim 1 , wherein the biodegradable ocular implant is a multi-layer film comprising the first layer, the multi-layer film being configured to be implanted within a subconjunctival space of an eye of a subject.

27. The biodegradable ocular implant of claim 26 , wherein the biodegradable ocular implant is configured to resume a desired shape after insertion into the subconjunctival space of the eye of the subject.

28. The biodegradable ocular implant of claim 27 , wherein the desired shape comprises a curved shape or a convex shape.

29. The biodegradable ocular implant of claim 27 , wherein the biodegradable ocular implant is configured to resume the desired shape when exposed to a temperature of about 37° C.

30. The biodegradable ocular implant of claim 1 , wherein each of the layers has a thickness of about 0.1 micron to about 10 microns.

31. The biodegradable ocular implant of claim 1 , wherein the biodegradable ocular implant has an overall thickness of about 1 mm to about 2 mm.

32. A method of forming a biodegradable ocular implant for sustained drug delivery, comprising:
(a) providing a first layer comprising a first biodegradable polymer; and
(b) loading the first biodegradable polymer with a drug.

33. The method of claim 32 , wherein providing the first layer comprises:
(a) dissolving the first biodegradable polymer in a suitable solvent to form a first solution; and
(b) evaporating the solvent to obtain the first layer.

34. The method of claim 33 , wherein loading comprises adding the drug to the first solution prior to evaporating the solvent.

35. The method of claim 32 , wherein loading comprises immersing the first layer in a solution containing the drug.

36. The method of claim 33 , wherein loading comprises simultaneously dissolving the drug and the first biodegradable polymer in the solvent prior to evaporating the solvent.

37. The method of claim 32 , further comprising:
(a) dissolving a second biodegradable polymer with a suitable solvent to form a second solution;
(b) casting the second solution on top of the first layer; and
(c) evaporating the solvent to form a top layer.

38. The method of claim 32 , further comprises forming a bottom layer on which the first layer is arranged, comprising:
(a) dissolving a third biodegradable polymer with a suitable solvent to form a third solution;

Assignees

• Univ Nanyang Tech
• Singapore Health Serv Pte Ltd

Inventors

• Venkatraman Subramanian
• Boey Yin Chiang Freddy
• Wong Tina
• Metha Jodhbir

Classifications

• B29K2995/006

  Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible · CPC title

• A61F9/0017

  implantable in, or in contact with, the eye, e.g. ocular inserts · CPC title

• A61L31/125

  having a macromolecular matrix · CPC title

• B29K2105/0035

  Medical or pharmaceutical agents · CPC title

• A61K31/5575

  having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha · CPC title