Bioresorbable microparticles

Patent metadata

Field	Value
Publication number	US-9919052-B2
Application number	US-201214128487-A
Country	US
Kind code	B2
Filing date	Jun 20, 2012
Priority date	Jun 23, 2011
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

Polyurethane microparticles are derived from structural units comprising poly(alkylene oxide) moieties, caprolactone moieties and urethane moieties. The microparticles may include an active agent and have a particle size from 0.1 to 100 microns. Microparticles for injection have a particle size of 15 to 80 microns; for use as a aerosol 1 to 3 microns; and for intraocular use 0.02 to 2 microns. Dispersivity is in the range 1 to 3.

First claim

The invention claimed is:

1. Polymer microparticles, the polymer being a polyurethane obtainable by reacting together:
(a) a prepolymer comprising co-polymerised units of a caprolactone and poly(alkylene oxide) moieties;
(b) a polycaprolactone diol comprising co-polymerised units of a caprolactone and a C 2 -C 6 diol; and
(c) a diisocyanate;
wherein the microparticles have a particle size of from 0.01 to 100 microns, and
wherein the microparticles have a dispersivity span in the range from 1 to 3;
wherein the dispersivity span is the width of particle size distribution as defined by the formula:

Span
=

D
⁡

[

v
,
0.9

]

-

D
⁡

[

v
,
0.1

]

D
⁡

[

v
,
0.5

]

wherein:
D(v, 0.5) is the median volume diameter wherein 50% of the particle size distribution has a volume-based diameter above the D(v,0.5) value and 50% is below;
D(v, 0.9) is the value wherein 90% of the particle size distribution has a volume-based diameter below the D(v, 0.9) value; and
D(v, 0.1) is the value wherein 10% of the particle size distribution has a volume-based diameter below the D(v,0.1) value.

2. The microparticles to claim 1 , which further comprise an active agent.

3. The microparticles to claim 2 , wherein the active agent is a protein or peptide.

4. The microparticles of claim 1 , in a formulation suitable for injection, having a particle size of 15 to 80 microns.

5. The microparticles of claim 1 , in an aerosolizable formulation that upon aerosolization provides an aerosol having an apparent aerodynamic diameter in the range 1 to 3 microns.

6. The microparticles of claim 1 , in a formulation suitable for intraocular use, having a particle size of 0.02 to 2 microns.

7. The microparticles of claim 1 , wherein after 1 month at 50° C. in phosphate buffered saline the reduction in average molecular weight of the polymer is 60 to 90%.

8. The microparticles of claim 1 , wherein after 6 months at 37° C. in phosphate buffered saline the reduction in average molecular weight of the polymer is 30 to 80%.

9. The microparticles of claim 1 , wherein the swellability in phosphate buffered saline at 37° C. is 10-100%.

10. The microparticles of claim 2 , wherein the active agent is released by 30 days nominally.

11. The microparticles of claim 1 , which become completely resorbed in the body of a human or animal patient.

12. A method for delivering an active agent to a patient comprising administering microparticles according to claim 2 to the patient.

13. The microparticles of claim 8 , wherein after 6 months at 37° C. in phosphate buffered saline the reduction in average molecular weight of the polymer is 40 to 70%.

14. The microparticles of claim 1 , wherein the dispersivity span is in the range 1.1-2.5.

15. The microparticles of claim 1 , wherein the dispersivity span is in the range 1.2-2.0.

16. The microparticles of claim 7 , wherein after 1 month at 50° C. in phosphate buffered saline the reduction in average molecular weight of the polymer is 70 to 85%.

17. The microparticles of claim 2 , wherein the active agent is released by 60 days nominally.

18. The microparticles of claim 2 , wherein the active agent is released by 90 days nominally.

19. The microparticles of claim 2 , wherein the active agent is released by 120 days nominally.

20. The microparticles of claim 1 , wherein the microparticles degrade in the physiological environment of animals.

21. The microparticles of claim 20 , wherein the time taken for the polymer to fully degrade is in the order of from 1 day to 250 weeks.

22. The microparticles of claim 1 , wherein the swellability in phosphate buffered saline at 37° C. is in the range from 1 to 500%.

23. The microparticles of claim 2 , wherein the overall time to release the active agent is in the order of hours.

24. The microparticles of claim 2 , wherein the overall time to release the active agent is in the order of days.

25. The microparticles of claim 2 , wherein the overall time to release the active agent is in the order of weeks.

26. The microparticles of claim 2 , wherein the overall time to release the active agent is in the order of months.

27. The microparticles of claim 2 , wherein the overall time to release the active agent is in the order of years.

28. The microparticles of claim 1 , wherein the poly(alkylene oxide) moieties are selected from a poly(C 2 -alkylene oxide), a poly(C 3 -alkylene oxide), and mixtures thereof.

29. The microparticles to claim 1 , wherein the C 2 -C 6 diol is selected from ethylene glycol and diethylene glycol.

Assignees

• Ross Alistair
• Law Jennifer S
• Mcinnes Fiona E
• Ferring Bv

Inventors

• Ross Alistair
• Law Jennifer S
• Mcinnes Fiona E

Classifications

• A61P5/10

  of the posterior pituitary hormones, e.g. oxytocin, ADH · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P27/02

  Ophthalmic agents · CPC title