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Use of cyclo tyrosine-valine and analog compounds to treat asthma and airway allergy

A technology of tyrosine and valine, applied in allergic diseases, respiratory diseases, drug combinations, etc., can solve problems such as adverse side effects

Active Publication Date: 2019-06-25
CHANG GUNG BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although many drugs are currently available to treat pulmonary allergy symptoms, such as anti-histamines, epinephrine, glucocorticoids, and anti-leukotriene drugs, these drugs only reduce symptoms severity and may have adverse side effects

Method used

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  • Use of cyclo tyrosine-valine and analog compounds to treat asthma and airway allergy
  • Use of cyclo tyrosine-valine and analog compounds to treat asthma and airway allergy
  • Use of cyclo tyrosine-valine and analog compounds to treat asthma and airway allergy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Cyclic tyrosine-valine inhibits Th2 cells from secreting inflammatory precursor hormones

[0036] In view of the immunological effects of Th2 cells regulating asthma in humans and animals, the effect of cyclic tyrosine-valine on Th2 cells in culture was tested in this example. First, naive T cells were isolated from BALB / c mice cultured on a culture medium containing anti-CD3 antibody (2 μg / ml), anti-CD28 antibody (2 μg / ml), anti-interferon-γ (IFN-γ) antibody (10 μg / ml), and IL-4 (10ng / ml) medium to induce T cells to differentiate into Th2 cells. The Th2 cells were treated with 2.3 μM cyclic tyrosine-valine (Cyclo Tyr-Val for short), cyclic alanine-isoleucine (Cyclo Ala-Ile), cyclic alanine-leucine (Cyclo Ala-Leu), cyclic tyrosine-leucine (Cyclo Tyr-Leu), cyclic alanine-phenylalanine (Cyclo Ala-Phe for short), or cyclic tyrosine-isoleucine Tyr-Ile (Cyclo Tyr-Ile) was treated for three days, and then the protein content of IL-4 was determined by enzyme-linked immunoso...

Embodiment 2

[0041] Cyclic tyrosine-valine inhibits airway hyperresponse (AHR) in mice

[0042] In view of the fact that one of the characteristics of asthma is the excessive response of the respiratory tract to irritants, this embodiment takes ovalbumin as an example of an allergen, and tests the effect of cyclic tyrosine-valine on stimulation by methacholine (Mch). Effects of Ovalbumin-Induced Airway Hyperresponse in Asthmatic Mice. First, BALB / c mice were given 50 μg of ovalbumin (Sigma, USA) and 0.8 mg of aluminum hydroxide (Thermo Fischer Scientific, USA) by intraperitoneal injection (intraperitoneal injection) on days 0, 1, 2, and 14. mixture, and on days 14, 17, 21, 24, and 27, the mice were given 2% ovalbumin with a nebulizer (Plumo-Aide 5650; Devilbiss, USA) for 20 minutes. Thereafter, on days 21 to 27, the vehicle (normal saline containing 0.5% DMSO) or cyclic tyrosine-valine at a dose of 0.11304, 1.1304, 11.304, or 113.04 nmol / kg body weight was injected intraperitoneally. The...

Embodiment 3

[0044] Cyclic tyrosine-valine reduces cellular infiltration, proinflammatory hormone secretion, and antibody production in mouse lungs

[0045] In view of the fact that one of the characteristics of asthma is the accumulation of immune cells including eosinophilic leukocytes in the lung tissue, this example detects the effect of cyclic tyrosine-valine on the number of cells in the lung washing fluid, and at the same time explores its effect on inflammation Effects of precursor hormone secretion and antibody production. First, ovalbumin-induced asthmatic mice (BALB / c mice) were established according to the method in Example 2. Vehicle (normal saline containing 0.5% DMSO) or cyclic tyrosine-valine at doses of 0.11304, 1.1304, 11.304, or 113.04 nmol / kg body weight were administered intraperitoneally daily on days 21 to 27 The ovalbumin-induced asthmatic mice were collected, and the lung washing fluid and serum of the mice or mice treated with saline (control group) were collecte...

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Abstract

The present invention provides a method to treat asthma and airway allergy by administering the dipeptide cyclo tyrosine-valine or a related cyclodipeptide compound to a subject in need thereof. Cyclotyrosine-valine or the related cyclodipeptide compound reduces Th2 cell activation, airway hyperresponsiveness, accumulation of immune cells in bronchoalveolar fluid, and allergen-specific antibody production in an animal or human subject. The compound can therefore be used to treat asthma and airway allergy.

Description

technical field [0001] The present invention relates to the use of a compound for treating asthma. In particular, it relates to the use of cyclic tyrosine-valine and its analogs for treating asthma and respiratory allergy. Background technique [0002] Asthma is a common disease state in which an inflammatory response occurs in the airways and lungs. Asthma is estimated to affect 235 to 330 million people worldwide and is responsible for 250,000 to 345,000 deaths each year. Notably, asthma is more prevalent in developed countries including the UK, New Zealand, the US, Canada, and Australia. Asthma patients often have symptoms such as coughing, wheezing, and shortness of breath, which greatly affect their quality of life and may even lead to complications and death. [0003] Asthma is characterized by the accumulation and activation of innate immune cells in the airway mucosa, including eosinophils, neutrophils, macrophages, and T cells, which Secretes a variety of immune...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/495A61P11/06A61P11/00A61P37/08
CPCA61K38/05A61P11/06
Inventor 柯云飞马奕安廖建清邱振尧林诠盛安路益谢珮文陈俞利张志荣吴宗儒欧大卫陆嘉真赖信志杨定一
Owner CHANG GUNG BIOTECH
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