Nanoparticulate and macroparticulate formulations

Patent metadata

Field	Value
Publication number	US-10201506-B2
Application number	US-201715425421-A
Country	US
Kind code	B2
Filing date	Feb 6, 2017
Priority date	Mar 12, 2013
Publication date	Feb 12, 2019
Grant date	Feb 12, 2019

Abstract

The present invention is directed to particles prepared via the polymerization of at least one surfactant and an isocyanate-containing compound. Pharmaceutical compositions prepared using these particles are also described.

First claim

What is claimed:

1. Particles comprising
a core comprising a therapeutic agent; and
a shell surrounding the core and comprising a polymer polymerized from
a compound comprising at least two isocyanate moieties; and
at least one polyhydric alcohol surfactant that is derived from a polyethoxylated sorbitan and oleic acid, a polyoxyethylene derivative of sorbitan monolaurate, a sorbitan ester, or a mixture thereof,
wherein the particles have an average diameter of between about 20 nm to about 800 nm.

2. The particles of claim 1 , wherein the therapeutic agent is water soluble.

3. The particles of claim 1 , wherein the therapeutic agent is a peptide or protein.

4. The particles of claim 1 , wherein the therapeutic agent is a polynucleotide.

5. The particles of claim 1 , wherein the therapeutic agent is a small molecule drug compound.

6. The particles of claim 1 , wherein the particles have an average diameter of between about 50 nm and about 300 nm, about 60 nm to about 600 nm, or about 20 nm to about 600 nm.

7. The particles of claim 1 , wherein the compound comprising at least two isocyanate moieties further comprises at least one pH-sensitive moiety.

8. The particles of claim 1 , wherein the compound comprising at least two isocyanate moieties further comprises at least one maleimide moiety.

9. The particles of claim 8 , wherein the at least one maleimide moiety serves as a linker to connect at least one pH-sensitive moiety to the compound.

10. The particles of claim 7 , wherein the pH-sensitive moiety is a tetrahydropyran moiety.

11. The particles of claim 1 , wherein the compound comprising at least two isocyanate moieties further comprises at least one water-solubilizing moiety.

12. The particles of claim 11 , wherein the at least one maleimide moiety serves as a linker to connect at least one water-solubilizing moiety to the compound.

13. The particles of claim 11 , wherein the at least one water-solubilizing moiety is a PEG moiety, a functionalized PEG moiety, or a mixture thereof.

14. The particles of claim 1 , wherein the compound comprising at least two isocyanate moieties has between four and ten isocyanate moieties.

15. The particles of claim 1 , wherein the compound comprising at least two isocyanate moieties is a diisocyanate.

16. The particles of claim 15 , wherein the compound comprising at least two isocyanate moieties is an alkyldiisocyanate.

17. The particles of claim 16 , wherein the compound comprising at least two isocyanate moieties is 1,6-hexyl diisocyanate.

18. The particles of claim 1 , wherein the particles are nanoparticles.

19. The particles of claim 1 , wherein the particles are nanocapsules.

20. The particles of claim 1 , wherein the polymeric shell comprises at least one targeting ligand.

21. A pharmaceutical composition comprising the particles of claim 1 and a pharmaceutically acceptable diluent or excipient.

22. A method of treatment comprising administering to a patient in need thereof, the pharmaceutical composition of claim 21 .

Assignees

• Cephalon Inc

Inventors

• Brown Peter D
• Drager Anthony S

Classifications

• C07D235/16

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• A61K9/145 Primary

  with organic compounds · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4184

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title