Methods for treating inflammatory conditions of the lungs

An inflammatory disease, lung technology, applied in chemical instruments and methods, anti-inflammatory agents, pharmaceutical formulations, etc.

Pending Publication Date: 2019-09-27
NOVOZYMES AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The concept of treating asthma by targeting a single cytokine such as anti-IL-4, anti-IL-5, anti-TNF-α has limited success

Method used

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  • Methods for treating inflammatory conditions of the lungs
  • Methods for treating inflammatory conditions of the lungs
  • Methods for treating inflammatory conditions of the lungs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0222] To identify and evaluate the efficacy of mammalian β-defensins in a murine infection-induced asthma model of severe steroid insensitivity, neutrophilic, allergic airway disease ( figure 1 ).

[0223] Materials and methods

[0224] treatment plan :

[0225]Female 6-8 week old BALB / c mice were sensitized intraperitoneally (IP) with 50 μg ovalbumin in 200 μL 0.9% saline with 1 mg adjuvant alum. Mice were challenged intranasally (IN) with Ova (10 μg Ova in 50 μL sterile saline) on days 12-13 and 33-34. On day 14, mice were inoculated intranasally with the natural mouse pathogen Chlamydia muridarum (Cmu: 100 inclusion body forming units, ATCC VR-123, 30 μL sucrose phosphate glutamate buffer (SPG)). Dexamethasone (DEX) (2 mg / kg; 50 μL phosphate-buffered saline (PBS)) was administered intranasally on days 32-34 of the challenge with Ova. hBD-2 (5 mg / kg; 50 μL phosphate-buffered saline) was administered intranasally on days 30, 32 and 34.

[0226] Drugs administered to m...

Embodiment 2

[0235] To determine and evaluate the efficacy of intranasally and orally administered mammalian β-defensins in a murine house dust mite / Freund's complete adjuvant-driven model of allergic asthma ( figure 2 ).

[0236] Materials and methods

[0237] treat Protocol: Female 7-10 week-old BALB / c mice were randomly assigned to 7 study groups one day before the start of the study and were infested with house dust mites (100 μg HDM in 200 μL saline plus Freund’s in 0.9% saline complete adjuvant) subcutaneous (SC) sensitization. Mice were then challenged intranasally (IN) on day 14 with HDM (25 μg HDM in 50 μL saline). On day 14, dexamethasone (1 mg / kg twice daily; 50 μL phosphate buffered saline (PBS)) was administered orally. hBD-2 was administered intranasally or orally on day 14 (1.7 mg / kg three times a day, intranasal; 0.4 mg / kg three times a day, intranasal; 0.4 mg / kg three times a day, orally, 50 μL phosphate-buffered saline ). The initial dose was administered 60 minut...

Embodiment 3

[0248] To identify and evaluate the efficacy of intranasal and oral mammalian β-defensins in a murine house dust mite / Freund's complete adjuvant-driven model of allergic asthma ( figure 2 ).

[0249] Materials and methods

[0250] treatment plan : Female 7-10 week-old BALB / c mice randomly assigned to one of the 4 study groups on the day before the start of the study were infected with house dust mites (100 μg HDM in 200 μL saline plus Freund’s complete adjuvant in 0.9% saline ) subcutaneous (SC) sensitization. Mice were challenged intranasally (IN) with HDM (25 μg HDM in 50 μL saline) on day 14. On day 14, hBD-2 was administered intranasally or orally (0.4 mg / kg three times a day intranasal; orally 0.4 mg / kg three times a day in 50 μL phosphate-buffered saline). The initial dose was administered 60 minutes prior to challenge, and subsequent doses were spaced approximately 6 hours apart.

[0251] test:

[0252] Lung Tissue Sampling: Lungs were removed from the chest c...

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Abstract

The present invention relates to methods for treatment or prevention of asthma, mild intermittent asthma, mild persistent asthma, moderate persistent asthma, severe persistent asthma, eosinophilic asthma, neutrophilic asthma, steroid refractory asthma, status asthmaticus, pneumonia, bronchiectasis, COPD, sarcoidosis, and lung cancer based on reducing airway hyper responsiveness, increasing pulmonary compliance, reducing lung inflammation, reducing inflammatory cell count in bronchoalveolar fluid and reducing cytokine production by administration of a mammalian alpha- and/or beta-defensin.

Description

technical field [0001] The present invention relates to a method for reducing airway hyperresponsiveness, increasing lung compliance, reducing lung inflammation, reducing perivascular or peribronchial inflammation, reducing bronchoalveolar fluid Inflammatory cell counts in and methods of treating or preventing pulmonary inflammatory conditions including asthma, mild intermittent asthma, Mild persistent asthma, moderate persistent asthma, severe persistent asthma, eosinophilic asthma, neutrophilic asthma, steroid-refractory asthma, status asthmaticus, pneumonia, bronchiectasis, COPD, and lung cancer . Background technique [0002] Asthma is a heterogeneous inflammatory disorder of the airways characterized by chronic inflammation, airway hyperresponsiveness, and symptoms of recurrent wheezing, coughing, and shortness of breath. Asthma is a major public health problem affecting 300 million people worldwide and its prevalence has increased substantially over the past three de...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P31/04A61P29/00A61P11/06
CPCA61K38/1729A61P31/04A61P29/00A61P11/06A61K47/64A61K9/0053A61K9/007A61K45/06C07K14/4723A61K38/38
Inventor P·诺德基尔德S·基亚罗夫
Owner NOVOZYMES AS
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