Dry powder inhaler and system for drug delivery

• US 9,446,133 B2
• Filed: 10/21/2014
• Issued: 09/20/2016
• Est. Priority Date: 06/13/2008
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Smutney, Chad C., Kinsey, P. Spencer, Sahi, Carl R., Adamo, Benoit, Polidoro, John M., McLean, Scott, Overfield, Dennis, Kraft, Kelly S., Somerville, Karla
• Primary Examiner(s): FISHER, ABIGAIL L
• Application Number:
  US14/520,185
• Publication Number:
  US 20150045295A1
• Time in Patent Office: 700 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/186 Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0023 retractable
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 15/0043 Non-destructive separation of the package, e.g. peeling
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/0048 the dosages being arranged in a plane, e.g. on diskettes
• CPC Class Codes: A61M 15/0086 Inhalation chambers
• CPC Class Codes: A61M 15/0091 mechanically breath-triggered
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/6081 Colour codes
• CPC Class Codes: A61M 2206/20 having means for promoting or enhancing the flow, actively or passively

Abstract

A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.

Claims

1. Fumaryl diketopiperazine (FDKP) microparticles comprising a trans isomer content of about 45% to 59% and further comprising an active agent.

2. The FDKP microparticles according to claim 1, wherein said trans isomer content is from about 49% to 58%.

3. The FDKP microparticles according to claim 1, wherein said trans isomer content is from about 53% to 56%.

4. The FDKP microparticles of claim 1 wherein the active agent comprises at least one of a protein, polypeptide, or peptide;

a nucleic acid;

a synthetic organic compound;

an inorganic compound;

a polysaccharide or other sugar;

a fatty acid;

a lipid;

heparin;

felbamate;

sumatriptan;

argatroban;

azidothymidine (AZT);

didanosine (DDI);

lamotrigine;

or an antibody or fragment thereof.

5. The FDKP microparticles of claim 4, wherein the active agent comprises a protein, polypeptide, or peptide.

6. The FDKP microparticles of claim 4, wherein the active agent comprises an antibody or fragment thereof.

7. The FDKP microparticles of claim 1 wherein the active agent comprises at least one of a vasoactive agent, a neuroactive agent, a hormone, an anticoagulant, an immunomodulating agent, a vaccine, an antibiotic, an anesthetic or sedative, a decongestant, antisense, a cytotoxic agent, an antiviral agent, or an antigen.

8. The FDKP microparticles of claim 7 wherein the active agent is a hormone.

9. The FDKP microparticles of claim 7 wherein the active agent is a vasoactive agent.

10. The FDKP microparticles of claim 1 wherein the active agent comprises at least one of a protein or peptide, or analogs, active fragments, or O-glycosylated forms thereof, wherein said protein or peptide is insulin erythropoietin, chorionic gonadotropin releasing factor, luteinizing releasing hormone, β

-galactosidase, exendin, anti-SSX-2_41-49 (synovial sarcoma, X breakpoint

     2), anti-NY-ESO-1 (esophageal tumor associated antigen), anti-PRAME (preferentially expressed antigen of melanoma), anti-PSMA (prostate-specific membrane antigen), anti-Melan-A (melanoma tumor associated antigen), anti-tyrosinase (melanoma tumor associated antigen), follicle stimulating hormone (FSH), Bruton'"'"'s tyrosine kinase (BTK), inositol-requiring kinase 1 (IRE1), a growth hormone, parathyroid hormone (PTH), parathyroid hormone related peptide (PTHrP), granulocyte macrophage colony stimulating factor (GM-CSF), glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXN), peptide YY(3-36) (PYY), calcitonin, or vasoactive intestinal peptide.

11. The FDKP microparticles of claim 10 wherein the active agent is oxyntomodulin.

12. The FDKP microparticles of claim 10 wherein the active agent is GLP-1.

13. The FDKP microparticles of claim 10 wherein the active agent is PYY.

14. A method of delivering an active agent comprising administering the microparticles of claim 10 to a person in need thereof.

15. The method of claim 14 wherein said microparticles are administered using an inhalation system for delivering a dry powder medicament to a pulmonary tract, the system comprising a dry powder inhaler configured to have at least two inlet apertures, wherein a first inlet aperture is in fluid communication with a first air flow pathway and a second inlet aperture is in fluid communication with a second air flow pathway, the second air flow pathway configured to bypass a container area, and wherein the first airflow pathway and the second air flow pathway converge in a substantially perpendicular manner;

and wherein the air flow pathway configured to bypass the container area delivers 30% to 90% of a total flow going through the inhaler during an inhalation.

16. The method of claim 15, said inhaler further comprising a container comprising a dry powder medicament mounted to the container area such that the container is in fluid communication with the first inlet aperture such that the first air flow pathway passes through the container before the first air flow pathway and the second air flow pathway converge.

17. The method of claim 15 wherein 10% to 70% of the total flow going through the inhaler during an inhalation transits through the container prior to merging with the second air flow pathway.