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Chemical-based Nitric Oxide Gas-generating Drug Device for the Treatment of Pulmonary Hypertension

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HL152921-01
Agency Tracking Number: R41HL152921
Amount: $465,219.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA19-270
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-08-10
Award End Date (Contract End Date): 2021-07-31
Small Business Information
Birmingham, AL 35242-2509
United States
DUNS: 081040477
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 (205) 934-7707
Business Contact
Phone: (205) 579-0183
Research Institution
1720 2ND AVE SOUTH, AB 1170
BIRMINGHAM, AL 35294-0001
United States

 Nonprofit College or University

Pulmonary hypertension (PH) is a highly debilitating disease that affects about 1% of the global
population, which increases up to 10% in individuals aged more than 65 years. The life
expectancy for these patients is less than 10 years after diagnosis, and no specific drugs are
available for pharmacologic treatment. Despite the introduction PDE5, prostacyclin analogs, and
endothelin antagonists, mortality remains high and quality of life poor. Therefore, inhalation and
aerosolization are the best options for administering drugs to treat/manage PH. In this context,
inhaled nitric oxide (iNO), a pulmonary-specific vasodilator, has been shown to be the best option
for treating PH without compromising systemic blood pressure. Current iNO therapy requires a
complex and expensive (approximately $180/hour) system of gaseous NO storage cylinders,
transportation, and devices to monitor and regulate the dilution and delivery of NO, O2, and
nitrogen dioxide (NO2). Therefore, this therapy is only in intensive care units and operating rooms
of established hospitals in developed countries. Consequently, the demand is high and the
opportunity large for new, inexpensive technologies that are less complex and portable for use in
and out of hospitals. Since 1999, when the FDA approved the use of iNO therapy, several start-
up companies have worked to develop such devices, but none has yet reached the market. We
intend to fill this gap with our technology. Low molecular weight S-nitrosothiols (SNO) can be
generated easily by reacting acidified nitrite with thiols in the laboratory. These SNO are not stable
and spontaneously decompose to NO and corresponding disulfides. Hence these SNO have
special ability to store and release NO. Our idea is to use this NO as a source of iNO therapy.
Our preliminary studies indicate that NO released from S-nitrosothiols can be removed
successfully from the reaction vessel and then introduced into carrier gas. Manipulating the
reaction conditions can sustain this NO for over 10 hours. The main goal of the phase 1 study is
to build prototype portable devices and then evaluate the purity of NO gas, as these are major
hindrance to developing any novel inhaled technologies and FDA approval. Nitrogen dioxide
(NO2) that forms as result of NO reaction with carrier gas, oxygen is a major toxic contaminant,
especially in noninvasive iNO therapy. This NO2 formation will be minimized by generating desired
levels of NO (NO2 formation is favored at higher NO concentrations) under anaerobic conditions
and deliver to patients without storage. NO2 formation will be measured at the pre-set and lung
level by direct and indirect methods via chemiluminescence assay and electrochemical sensors,
respectively. A benchtop noninvasive iNO delivery system that simulates iNO delivery to patients
will be used to evaluate the purity of gas and function of devices. Establishing the purity of gas
and prototype device functions are an imperative before investing time and money in developing
a final full-scale product. In summary our technology will deliver sustained, tunable levels of iNO
with portability, increased safety (minimum or none toxic gases), less expensively, without the
use of bulky cylinders.PROJECT NARRATIVE
Inhaled nitric oxide (iNO) therapy, a pulmonary specific vasodilator is a lifesaving drug for hypoxic lung failure
associated with pulmonary hypertension (PH) and life-threatening PH and right heart failure. This treatment
currently requires a complex iNO delivery system and is available only in the intensive care units and operating
rooms in the major hospitals of developed countries. The goal of this investigation is to develop portable devices
that use chemical reactions to generate NO locally for delivery to wider population of PH patients in and out of
hospitals whenever and wherever it is needed.

* Information listed above is at the time of submission. *

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