High capacity diketopiperazine microparticles and methods

Patent metadata

Field	Value
Publication number	US-11433135-B2
Application number	US-202016739506-A
Country	US
Kind code	B2
Filing date	Jan 10, 2020
Priority date	Jun 17, 2011
Publication date	Sep 6, 2022
Grant date	Sep 6, 2022

Abstract

Disclosed herein are diketopiperazine microparticles having high capacity for adsorbing a drug or active agent. In particular, the diketopiperazine microparticle are formed using fumaryl diketopiperazine and can comprise a drug in large doses for the treatment of disease or disorders by pulmonary delivery via oral inhalation.

First claim

What is claimed is:

1. A drug deliverable agent for pulmonary inhalation for treating disease, the drug deliverable agent comprising:
diketopiperazine microparticles; wherein said diketopiperazine microparticles comprise
a specific surface area greater than about 70 m 2 /g,
a mass-weighted average particle size of about 33,000 to about 216,000 voxels measured by X-ray tomography for particle size measuring about 0.5 μm to about 4 μm in geometric diameter,
a plurality of structural domains having one or more cores surrounded by layers of a porous crystalline material, and
a concentration of an active ingredient, or analog thereof, of about 18% to about 25% by weight of said microparticle.

2. The drug deliverable agent of claim 1 , wherein said diketopiperazine microparticles comprise a voxel-weighted average domain size of about 300 nm to about 400 nm.

3. The drug deliverable agent of claim 1 , wherein said diketopiperazine is fumaryl diketopiperazine (3,6-bis(N-fumaryl-4-aminobutyl)-2,5-diketopiperazine; or salt thereof.

4. The drug deliverable agent of claim 1 , wherein said active ingredient is a small organic molecule.

5. The drug deliverable agent of claim 1 , wherein said active ingredient is a neurotransmitter, pain relief agent, vasoactive agent, immunosuppressing agent, anti-cancer agent, vaccine, nucleic acid molecule or prophalactive agent.

6. The drug deliverable agent of claim 1 , wherein said active ingredient is a triptan selected from sumatriptan, rizatriptan and salts thereof.

7. The drug deliverable agent of claim 1 , wherein said active ingredient is a peptide wherein the peptide is insulin, glucagon, glucagon-like peptide-1, oxyntomodulin, peptide YY(3-36), ghrelin, vasoactive intestinal peptide, oxytocin or CCK.

8. The drug deliverable agent of claim 1 , wherein said active ingredient is insulin.

9. The drug deliverable agent of claim 8 , wherein said fumaryl diketopiperazine comprises an insulin content greater than about 4 U/mg.

10. The drug deliverable agent of claim 1 , wherein the diketopiperazine microparticles comprise structural domains ranging in number-weighted size from about 250 voxels to about 1,400 voxels.

11. The drug deliverable agent of claim 1 , wherein the diketopiperazine microparticles comprise structural domains ranging in voxel-weighted size from about 500 voxels to about 2,000 voxels.

12. The drug deliverable agent of claim 1 , wherein the plurality of structural domains have an average size from about 300 nm to about 450 nm as measured by radius of gyration.

13. The drug deliverable agent of claim 1 , further comprising a surfactant.

14. The drug deliverable agent of claim 13 , wherein the surfactant is polysorbate 80.

15. The drug deliverable agent of claim 1 , wherein the deliverable agent is in an inhalable dry powder form.

16. The drug deliverable agent of claim 15 , wherein the deliverable agent is capable of delivery to a patient in a single inhalation to the deep lung using a dry powder inhaler.

Assignees

• Mannkind Corp

Inventors

• Grant Marshall
• Menkin Paul
• Stowell Grayson W

Classifications

• Y10T428/2982

  Particulate matter [e.g., sphere, flake, etc.] · CPC title

• A61P5/18

  of the parathyroid hormones · CPC title

• A61K9/50

  Microcapsules {having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals (A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167)} · CPC title

• A61K9/00

  Medicinal preparations characterised by special physical form {(nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12)} · CPC title

• A61K38/28

  Insulins · CPC title