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Novel use of cannabinoid receptor agonist

An inhibitory and irritative technology, applied in the direction of anti-inflammatory agents, medical preparations containing active ingredients, non-central analgesics, etc., can solve the problem of no description of inhibitory active mucus secretion inhibitory activity

Inactive Publication Date: 2006-11-22
SHIONOGI & CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the inhibitory activity against the infiltration of inflammatory cells in the respiratory tract and the mucus secretion inhibitory activity are not described in these documents

Method used

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  • Novel use of cannabinoid receptor agonist
  • Novel use of cannabinoid receptor agonist
  • Novel use of cannabinoid receptor agonist

Examples

Experimental program
Comparison scheme
Effect test

experiment Embodiment 1、2 and 3

[0277] Experimental Examples 1, 2 and 3: Effects on antigen-induced bronchial hyper-irritability, inflammatory cell infiltration and mucus secretion (acute model) in BN rats

[0278] Antigen-induced bronchial hyper-irritability in BN rats: Brown Norway (BN) rats (Charles River) were injected intraperitoneally with 1 mL of a mixture containing aluminum hydroxide gel (1 mg) and egg white protein (0.1 mg, OVA). Japan) was actively sensitized. Ten days later, the antigen challenge was performed by inhaling the atomized 1% OVA solution using an ultrasonic nebulizer for 30 minutes. 24h after antigen challenge, under pentobarbital sodium anesthesia (80mg / kg, intraperitoneal injection), rats were injected intravenously with ACh by increasing the dose of ACh every 5min, and then by Konzett&Rssler with some modifications The method measures the bronchoconstrictor response observed immediately after each ACh injection. Briefly, the rat’s trachea was cut and a cannula was connected to the lu...

experiment Embodiment 4、5 and 6

[0286] Experimental Examples 4, 5, and 6: Effects on antigen-induced bronchial hyper-irritability, inflammatory cell infiltration and mucus secretion (chronic model) in BN rats

[0287] Antigen-induced bronchial hyper-irritability in BN rats: BN rats are actively sensitized by intraperitoneal injection of a mixture containing aluminum hydroxide gel and egg white protein. Twelve days later, the antigen challenge was performed by using an ultrasonic nebulizer (NE-U12, Omron) to inhale a nebulized 1% OVA solution or physiological saline for 30 minutes. In order to establish a model of chronic bronchial hyperstress, the procedure was repeated 3 times at 1 week intervals. From the day of the third antigen challenge, the test compound was orally administered for 8 days. On the day of the third antigen challenge, 1 h before the challenge, the test compound was administered. One hour after the last administration of the test compound, a fourth antigen challenge was performed. 24 hours aft...

experiment Embodiment 7、8 and 9

[0294] Experimental Examples 7, 8 and 9: Effects on antigen-induced bronchial hyper-irritability, inflammatory cell infiltration and mucus secretion (acute model) in guinea pigs

[0295]Excessive bronchial irritability induced by antigen in guinea pigs: At 1 week intervals, the guinea pigs trapped in the aeration chamber ( Charles River Japan) was actively sensitized. One week later, antigen challenge was performed by inhaling atomized 1% OVA generated by an ultrasonic nebulizer for 5 minutes. One hour before antigen challenge, the test compound was administered orally. In addition, guinea pigs were treated with diphenhydramine (10 mg / kg, intraperitoneal injection) and antihistamines 10 min before antigen challenge to prevent allergic death of the animals. 24h after antigen challenge, under urethane anesthesia (1.4g / kg, peritoneal injection), guinea pigs were injected intravenously with ACh by increasing the dose of ACh every 5min, and then by the Konzett & Rssler method with som...

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Abstract

An inhibitor for inflammatory cellular infiltration in the respiratory tract, inhibitor for hyperirritability in the respiratory tract, muciparous inhibitor, or bronchodilator which contains as an active ingredient a compound selected from the group of compounds represented by the formulae (I) and (II).

Description

Technical field [0001] The present invention relates to an airway inflammatory cell infiltration inhibitor, an airway hyperirritability inhibitor, a mucus secretion inhibitor or a bronchodilator containing a compound having cannabinoid receptor antagonistic activity as an active ingredient. Background technique [0002] In Patent 1 and Non-Patent 1, it is described that (R)-methandamide is a cannabinoid receptor modulator and a cannabinoid receptor antagonist, which shows an inhibitory activity against excessive respiratory tract stress. In addition, in Non-Patents 1, 2, 3, 4, and 5, it is described that cannabinoids, anandamide, nabilone, and CP55, 940 as cannabinoid receptor antagonists exhibit inhibitory activity on bronchial smooth muscle contraction. However, these documents do not describe the inhibitory activity against inflammatory cell infiltration of the respiratory tract and the mucus secretion inhibitory activity. In Patent 2, it is described that a cannabinoid recept...

Claims

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Application Information

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IPC IPC(8): A61K31/5415A61K31/435A61P11/04A61P11/08A61P29/00A61P43/00C07D279/06
CPCA61K31/435A61K31/5415A61P11/04A61P11/08A61P11/10A61P11/12A61P11/14A61P29/00A61P43/00C07D279/06
Inventor 有村昭典
Owner SHIONOGI & CO LTD
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