University of Michigan

Respira Therapeutics, Inc.

Histosonics, Inc.

The United States Government As Represented by the Department of Veterans Affairs

Zhen Xu

Charles A Cain

Adam D Maxwell

Martin J Donovan

Robert Curtis

Hugh Smyth

Hitinder S Gurm

Revati Shreeniwas

Timothy L Hall

Dan Deaton

James Hannon

Aileen Gibbons

Jeffry G Weers

J Brian Fowlkes

William W Roberts

Alain Romero

Adaani Frost

Pravin L Soni

Jonathan Sukovich

Kuang-Wei Lin

Stephen Lermer

Aditya S Pandey

Thomas W Davison

Dejan Teofilovic

Ryan M Miller

Michael Thomas Kusner, Jr

Yohan Kim

Tzu-Yin Wang

Simone Park

Clifford Suhyun Cho

Jonathan Jenner Macoskey

Novel dry powder compositions comprising and methods relating thereto are provided. The dry powder compositions comprise PDE5 inhibitors, such as vardenafil, or pharmaceutically acceptable salts or esters thereof. The dry powder compositions may optionally include an carrier/excipient. The concentration of active agent may be at least about 2% by weight. Methods of aerosolizing the dry powder compositions and using them to treat various diseases are also disclosed.

PDE5 inhibitor powder formulations and methods relating thereto

Apparatus and methods are provided for applying ultrasound pulses into tissue or a medium in which the peak negative pressure (P−) of one or more negative half cycle(s) of the ultrasound pulses exceed(s) an intrinsic threshold of the tissue or medium, to directly form a dense bubble cloud in the tissue or medium without shock-scattering. In one embodiment, a microtripsy method of Histotripsy therapy comprises delivering an ultrasound pulse from an ultrasound therapy transducer into tissue, the ultrasound pulse having at least a portion of a peak negative pressure half-cycle that exceeds an intrinsic threshold in the tissue to produce a bubble cloud of at least one bubble in the tissue, and generating a lesion in the tissue with the bubble cloud. The intrinsic threshold can vary depending on the type of tissue to be treated. In some embodiments, the intrinsic threshold in tissue can range from 15-30 MPa.

Histotripsy using very short ultrasound pulses

A histotripsy therapy system configured for the treatment of tissue is provided, which may include any number of features. Provided herein are systems and methods that provide efficacious non-invasive and minimally invasive therapeutic, diagnostic and research procedures. In particular, provided herein are optimized systems and methods that provide targeted, efficacious histotripsy in a variety of different regions and under a variety of different conditions without causing undesired tissue damage to intervening/non-target tissues or structures.

Ultrasound transducer with transmit-receive capability for histotripsy

Methods for performing non-invasive thrombolysis with ultrasound using, in some embodiments, one or more ultrasound transducers to focus or place a high intensity ultrasound beam onto a blood clot (thrombus) or other vascular inclusion or occlusion (e.g., clot in the dialysis graft, deep vein thrombosis, superficial vein thrombosis, arterial embolus, bypass graft thrombosis or embolization, pulmonary embolus) which would be ablated (eroded, mechanically fractionated, liquefied, or dissolved) by ultrasound energy. The process can employ one or more mechanisms, such as of cavitational, sonochemical, mechanical fractionation, or thermal processes depending on the acoustic parameters selected. This general process, including the examples of application set forth herein, is henceforth referred to as 'Thrombolysis.'

Histotripsy for thrombolysis

Provided herein are methods for treating pulmonary hypertension. The methods include administering to a subject in need thereof an effective amount of a vasodilator, wherein the vasodilator is administered to the subject via inhalation pro re nata using a portable inhaler. In some embodiments, the vasodilator is a PDE5 inhibitor. Pharmaceutical compositions for pro re nata administration of vasodilators are also described.

Methods and compositions for treatment of pulmonary hypertension and other lung disorders

A histotripsy therapy system configured for the treatment of brain tissue is provided, which may include any number of features. In one embodiment, the system includes an ultrasound therapy transducer, a drainage catheter, and a plurality of piezoelectric sensors disposed in the drainage catheter. The ultrasound therapy is configured to transmit ultrasound pulses into the brain to generate cavitation that liquefies a target tissue in the brain. The drainage catheter is configured to detect the ultrasound pulses. An aberration correction algorithm can be executed by the system based on the ultrasound pulses measured by the drainage catheter to automatically correct for an aberration effect caused by the ultrasound pulses passing through a skullcap of the patient.

Histotripsy therapy systems and methods for the treatment of brain tissue

Apparatus and methods are provided for applying ultrasound pulses into tissue or a medium in which the peak negative pressure (P&#x2212;) of one or more negative half cycle(s) of the ultrasound pulses exceed(s) an intrinsic threshold of the tissue or medium, to directly form a dense bubble cloud in the tissue or medium without shock-scattering. In one embodiment, a microtripsy method of Histotripsy therapy comprises delivering an ultrasound pulse from an ultrasound therapy transducer into tissue, the ultrasound pulse having at least a portion of a peak negative pressure half-cycle that exceeds an intrinsic threshold in the tissue to produce a bubble cloud of at least one bubble in the tissue, and generating a lesion in the tissue with the bubble cloud. The intrinsic threshold can vary depending on the type of tissue to be treated. In some embodiments, the intrinsic threshold in tissue can range from 15-30 MPa.

Systems and methods for histotripsy and immunotherapy are provided. In some embodiments, histotripsy can be applied to a target tissue volume to lyse and solubilize the target tissue volume to release tumor antigens. In some embodiments, an immune response of the treatment can be evaluated. In other embodiments, an immune therapy can be applied after applying the histotripsy. In one embodiment, the lysed and solubilized cells can be extracted from the tissue. The extracted cells can be used to create immune therapies, including vaccines.

Systems and methods for histotripsy immunosensitization

A dry powder inhaler includes a powder storage element configured to hold a powdered medicament and an inlet channel receives powdered medicament from the powder storage element that is entrained in an airflow. The inlet channel has a first diameter and defines an opening. The inhaler includes a dispersion chamber that receives the airflow and the powdered medicament from the opening. The dispersion chamber has a second diameter. The inhaler includes an actuator housed within the dispersion chamber. The actuator oscillates within the dispersion chamber when exposed to the airflow to deaggregate the powdered medicament entrained by the airflow passing through the dispersion chamber. A ratio between the first diameter and the second diameter is between about 0.40 and 0.60 such that an audible sound is produced as the actuator oscillates. The inhaler includes an outlet channel through which the airflow and powdered medicament exit the inhaler.

Powder dispersion methods and devices

Growing community of inventors

Ann Arbor, MI, United States of America

Zhen Xu