Methods for the systemic delivery of therapeutic agents to the pulmonary system using a droplet delivery device

Patent metadata

Field	Value
Publication number	US-2019125986-A1
Application number	US-201716098802-A
Country	US
Kind code	A1
Filing date	May 3, 2017
Priority date	May 3, 2016
Publication date	May 2, 2019
Grant date	—

Abstract

A droplet delivery device and related methods for delivering precise and repeatable dosages to a subject for pulmonary use is disclosed. The droplet delivery device includes a housing, a reservoir, and ejector mechanism, and at least one differential pressure sensor. The droplet delivery device is automatically breath actuated by the user when the differential pressure sensor senses a predetermined pressure change within housing. The droplet delivery device is then actuated to generate a stream of droplets having an average ejected droplet diameter within the respirable size range, e.g, less than about 5 μm, so as to target the pulmonary system of the user.

First claim

What is claimed:

1 . A method for the systemic delivery of a therapeutic agent as an ejected stream of droplets in a respirable range to the pulmonary system of a subject for the treatment of a disease, disorder or condition, the method comprising:
(a) generating an ejected stream of droplets via a piezoelectric actuated droplet delivery device, wherein at least about 70% of the ejected stream of droplets have an average ejected droplet diameter of less than about 5 μm; and (b) delivering the ejected stream of droplets to the pulmonary system of the subject such that at least about 70% of the mass of the ejected stream of droplets is delivered in a respirable range to the pulmonary system of a subject during use to thereby systemically delivery the therapeutic agent to the subject to treat the disease, disorder or condition.

2 . The method of claim 1 , wherein disease, disorder or condition is selected from diabetes mellitus, rheumatoid arthritis, plaque psoriasis, Crohn's disease, hormone replacement therapy, neutropenia, nausea, and influenza.

3 . The method of claim 1 , wherein the therapeutic agent is a therapeutic peptide, protein, antibody, or other bioengineered molecule.

4 . The method of claim 1 , wherein the therapeutic agent is selected from growth factors, insulin, vaccines, antibodies, Fc-fusion protein, hormones, enzymes, gene therapies and RNAi cell therapies, antibody-drug conjugates, cytokines, anti-infective agents, polynucleotides, oligonucleotides, or any combination thereof.

5 . The method of claim 1 , wherein the therapeutic agent is delivered to the pulmonary system of the subject at a reduced dosage, as compared to oral or intravenous dosages.

6 . The method of claim 1 , wherein the ejected stream of droplets are subjected to an approximate 90 degree change of trajectory within the piezoelectric actuated droplet delivery device such that droplets having a diameter greater than about 5 μm are filtered from the ejected stream of droplets due to inertial forces, without being carried in entrained airflow through and out of the piezoelectric actuated droplet delivery device to the pulmonary system of the subject.

7 . The method of claim 6 , wherein the filtering of droplets having a diameter greater than about 5 μm increases the mass of the ejected stream of droplets delivered to the pulmonary system of the subject during use.

8 . The method of claim 1 , wherein the ejected stream of droplets is delivered over a period of time less than about 2 seconds.

9 . The method of claim 1 , wherein the piezoelectric actuated droplet delivery device comprises:
a housing; a reservoir disposed within or in fluid communication with the housing for receiving a volume of fluid; an ejector mechanism in fluid communication with the reservoir, the ejector mechanism comprising a piezoelectric actuator and an aperture plate, the aperture plate having a plurality of openings formed through its thickness and the piezoelectric actuator operable to oscillate the aperture plate at a frequency to thereby generate an ejected stream of droplets; at least one differential pressure sensor positioned within the housing, the at least one differential pressure sensor configured to activate the ejector mechanism upon sensing a pre-determined pressure change within the housing to thereby generate an ejected stream of droplets.

10 . The method of claim 9 , wherein the aperture plate of the piezoelectric actuated droplet delivery device comprises a domed shape.

11 . The method of claim 9 , wherein the piezoelectric actuated droplet delivery device further comprising a laminar flow element located at the airflow entrance side of the housing and configured to facilitate laminar airflow across the exit side of aperture plate and to provide sufficient airflow to ensure that the ejected stream of droplets flows through the droplet delivery device during use.

Assignees

• Pneuma Respiratory Inc

Inventors

• Germinario Louis Thomas
• Hebrank John H
• Hunter Charles Eric
• Stern Thomas P

Classifications

• B05B7/0012

  Apparatus for achieving spraying before discharge from the apparatus · CPC title

• A61M2205/276

  preventing unwanted use · CPC title

• A61M2016/0036

  in the breathing tube and used in both inspiratory and expiratory phase · CPC title

• A61M2230/06

  Heartbeat rate only · CPC title

• A61M2205/8206

  battery-operated · CPC title