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Inhalation of nitric oxide for treating respiratory diseases

a technology of nitric oxide and respiratory diseases, applied in the field of therapy, can solve the problems of reduced oxygen transport and limited treatment of adults' respiratory diseases, and achieve the effect of safe

Inactive Publication Date: 2015-02-05
ADVANCED INHILATION THERAPIES AIT LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a safe and effective method for administering gaseous nitric oxide (gNO) to human subjects without causing significant changes in various physiological parameters. The method involves intermittent inhalation of gNO at a concentration of at least 160 ppm for at least one off-site parameter, such as methemoglobin level, end-tidal CO2 level, or inflammatory markers' level. The method can be used to treat and prevent various medical conditions in which nitric oxide inhalation has been shown to have therapeutic effects. The invention also provides a method for monitoring various parameters, such as methemoglobin level, oxygen saturation level, or urine nitrite level, in real-time during the intermittent inhalation of gNO. The method is safe and effective, and can be easily adapted for use in various settings.

Problems solved by technology

Potential side effects of high dose NO treatment hence include the binding of NO to hemoglobin and the formation of MetHb, which could lead to decreased oxygen transport, and the capacity of NO to act as a nitrosylating agent on proteins and other cell constituents.
However, other studies have shown that at such low concentration of inhaled gNO, treatment of adults' respiratory diseases is limited, and the use of higher doses of gNO for treating various medical conditions by inhalation requires in-depth safety studies in humans.

Method used

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  • Inhalation of nitric oxide for treating respiratory diseases
  • Inhalation of nitric oxide for treating respiratory diseases
  • Inhalation of nitric oxide for treating respiratory diseases

Examples

Experimental program
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Effect test

example 1 (

Background Art)

Determination of Effective Antimicrobial Level of gNO

[0323]The direct effect of gNO on bacteria was studied by determining the concentration of gNO which is lethal for microbes. Once an optimal dose was estimated, timing study was conducted to optimize the duration of exposure of the microbes to gNO.

[0324]For these initial studies, highly dense inoculums of P. aeruginosa and S. aureus suspensions (108 chum) were plated onto agar plates. These plates were then exposed to various concentrations of gNO in an exposure device in order to evaluate the effect on colony growth.

[0325]FIGS. 1A-B present bar-plot showing the gNO dosage curve on as measured for S. aureus (FIG. 1A) and P. aeruginosa (FIG. 1B) grown on solid media, wherein relative percentage of growth of colony forming units (CFU) at 50, 80, 120 and 160 parts per million (ppm) of gaseous nitric oxide (gNO) compared with growth of CFU in medical air (100%).

[0326]As can be seen in FIGS. 1A-B, the results confirmed t...

example 2

Determination of Effective Antiviral Level of gNO

[0335]The efficacy of treating human influenza A with gNO has been studied. Two strains (H3N2 and H7N3) of the virus were studied and showed that treating influenza virions or incubated cells with 160 ppm exogenous gNO reduced not only viral replication but also their infectivity in a Madin-Darby Canine Kidney (MDCK) cell to model of infection. gNO has been demonstrated as an effective anti-viral agent in both human Influenza A and highly pathogenic avian influenza.

[0336]The viruses used for the following experiments were from freezer stocks containing 1×106-1×107 pfu's / ml.

[0337]A standard plaque assay was used for the study. Frozen stock solutions of virions were diluted 1:10 in PBS and 3 ml were placed in each well of six well trays. The samples were either exposed to 160 ppm gNO or medical air at 37° C. Following exposure 0.5 ml was inoculated onto confluent MDCK cells, grown in six well trays, and incubated at 37° C. for 1 hour. ...

example 3

Administration of gNO to Healthy Human Subjects

[0344]Cohort:

[0345]10 healthy adult volunteer subjects (5 males, 5 females), aged 20 to 62 years, were enrolled in the study after screening their medical history, a physical examination, pulmonary function tests and blood values. Exclusion criteria included individuals less than 19 years of age, pregnant females and unwilling to practice birth control during the study, diagnosed with pulmonary disease, epistaxis, hemoptysis, methemoglobinemia, organ transplant recipient or receiving antibiotic therapy.

[0346]Regimen and Post-Treatment:

[0347]After obtaining informed consent, treatment was initiated within 5 days of enrollment. Subjects were housed in a hospital ward and received 160 ppm gNO for 30 minutes every four hours (Q4h), five times a day, for five consecutive days by inhalation. Subjects returned for follow-up evaluations 3, 7 and 21 days after the final gNO administration. Subject safety was determined by monitoring vital signs,...

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PUM

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Abstract

A method of treating a human subject which is effected by intermittent inhalation of gaseous nitric oxide at a concentration of at least 160 ppm is disclosed. The method can be utilized for treating a human subject suffering from, or prone to suffer from, a disease or disorder that is manifested in the respiratory tract, or from a disease or disorder that can be treated via the respiratory tract. The disclosed method can be effected while monitoring one or more of on-site and off-site parameters such as vital signs, methemoglobin levels, pulmonary function parameters, blood chemistry and hematological parameters, blood coagulation parameters, inflammatory marker levels, liver and kidney function parameters and vascular endothelial activation parameters, such that no substantial deviation from a baseline in seen in one or more of the monitored parameters.

Description

FIELD AND BACKGROUND OF THE INVENTION[0001]The present invention, in some embodiments thereof, relates to therapy, and more particularly, but not exclusively, to methods and devices for treating respiratory diseases by inhalation of gaseous nitric oxide.[0002]Nitric oxide (NO) is a small lipophilic signaling molecule with a small stokes radius and a molecular weight of 30 grams / mol that enables it to cross the glycolipid cell plasma membrane into the cytosol readily and rapidly. NO has an unpaired electron available in its outer orbit that characterizes it as a free radical. NO has been shown to play a critical role in various bodily functions, including the vasodilatation of smooth muscle, neurotransmission, regulation of wound healing and immune responses to infections such as caused by bactericidal action directed toward various organisms. NO has been demonstrated to play an important role in wound healing through vasodilatation, angiogenesis, anti-inflammatory and antimicrobial ...

Claims

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Application Information

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IPC IPC(8): A61M16/12A61M16/00
CPCA61M16/12A61M16/0003A61M2202/0275A61M2230/207A61M2230/205A61M2230/432A61M2205/3303A61M2202/0007A61K33/00A61P11/00A61P11/08A61P31/00A61M1/00A61K9/007A61M16/122A61B5/0833A61B5/0836A61B5/14507A61B5/14542A61B5/4244A61M2230/202
Inventor AV-GAY, YOSSEFMILLER, CHRISTOPHER C.GREENBERG, DAVID
Owner ADVANCED INHILATION THERAPIES AIT LTD
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