JPH0278618A - Antiallergic agent - Google Patents

Abstract

PURPOSE:To obtain an antiallergic agent having low toxicity, suppressing the fit of asthma caused by prostaglandin D2 at a low dose and useful as an antiasthmatic agent by using a specific compound as an active component. CONSTITUTION:The objective agent contains a compound of formula I (n is 2-6, preferably 3-5), e.g., 7-phenyl-7-(3-pyridyl)-6-heptenoic acid or its pharmacologically allowable salt as an active component. The compound of formula I can be produced by reacting the compound of formula II with a compound of formula III (X<-> is halogen ion). The active component may be used as it is or mixed with a carrier or an adjuvant and is safely administered to mammals including human by oral or parenteral administration in the form of capsule, liquid, injection, suppository, inhalant, etc. In the case of oral administration, the agent is preferably administered once or twice a day at a dose of 0.1-100mg of the active component per 1kg of body-weight per dose.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an antiallergic agent that has therapeutic and preventive effects on bronchial asthma, endotoxic shock caused by immediate allergies, and the like.

[Prior art] Recently, prostagranges generated from arachidonic acid:/
(PG'S), thromboxanes (TX's), leukotrienes (LT's), hydroxyeicosaben citrate (HETE'8), etc. and platelet activating factor (PAF) are important chemicals in respiratory diseases. It is becoming clear that, as a mediator, it is deeply involved in the onset, progression, and exacerbation of pathological conditions such as asthma (Nakano and Akimasa Miyamoto: Clinical Immunology, Vol. 20).

5upp1. , pl-10, 1988). These chemical mediators can be used to treat hypoxic/hyperoxic conditions, trauma,
It is believed that chemicals are released from cell groups, mainly white blood cells, when the immune system responds excessively due to inflammation or contact with pathogenic antigens (allergens).In fact, chemicals in the body fluids of asthma patients It has been reported that the content of mediator is increasing (M, C,
Liu, E., and R. Bleecker.

D, Proud, T, L, McLemore,
f, C, Ilubbard Prostagland
ins, vol, 35, p67-79, 19
88). Imidazole compounds are known as drugs that suppress asthma-inducing effects caused by chemical mediators such as LT'5SHETE's and PAF [JP-A-57-131769. Special Publication No. 60-50190, Special Publication No. 62-2587, etc.], Prostaglandin D! (
There is no known substance that suppresses the asthma-inducing effect caused by PGDJ.

[Problems to be Solved by the Invention] The present invention provides an antiallergic agent that can suppress asthma induction caused by PGDt.

[Means for Solving the Problems] The present invention is an antiallergic agent containing a compound represented by the general formula (wherein n represents an integer of 2 to 6) as an active ingredient.

The compound represented by the general formula (1) according to the present invention can be produced by the following method described in JP-A-58-219162.

(In the formula, n has the same meaning as in the previous description, and X″″ represents a halogen ion.)
The airway constriction reaction induced by PGD t) is suppressed at low doses. Among the compounds (+) used as active ingredients in the present invention, those in which n is an integer of 3 to 5 are preferred.

Compound (1) used as an active ingredient in the present invention
has low toxicity (e.g. LD of 7-phenyl-7-(3-pyridyl)-6-heptenoic acid in rats (male)).
so is 4590 mg/kg), as it is or mixed with known pharmaceutically acceptable carriers, excipients, etc. Pharmaceutical compositions [e.g., tablets, capsules (including soft capsules and microcapsules), liquid preparations, injections, suppositories,
It can be safely administered to mammals including humans orally or parenterally as an inhalant. The dosage varies somewhat depending on the subject, administration route, symptoms, etc., but for example, when orally administered to adult patients, a single dose is usually about 0.1 mg/kg to 100 D/kg body weight, preferably about 1 mg/kg-100 D/kg body weight. 5 mg/kg-50mg/kg
It is convenient to administer about the same amount as body weight once or twice a day.

Next, the present invention will be specifically explained with reference to Examples and Experimental Examples.

Example 1 (Tablet) 7-phenyl-7-(3-pyridyl)-6-hebutenoic acid 30 mg lactose
74 mg starch
15.6 mg starch (for paste production) 5 mg magnesium stearate 5 mg calcium salt of 0.4D carboquinomethyl cellulose Total 150 mg The above components were mixed and made into tablets according to a conventional method.

Example 2 (Dragage-coated tablet) Tablet (Example 1) 150 m
g talc 30 mg
Gum arabic 6 mg Sucrose 74 mg Total 26
0 mg The tablets produced in Example 1 were coated with the above ingredients in a conventional manner to make sugar-coated tablets.

Example 3 (Capsule) 7-phenyl-7-(3-pyridyl)-6~heptenoic acid 10 mg Microcrystalline cellulose 30 mg Lactose
57 mg total 100 m
g The above ingredients were mixed according to a conventional method and filled into gelatin capsules to prepare capsules.

Example 4 (Injection) (1) (E)-7-phenyl-7-(3-pyridyl)-
6-hebutanoic acid 2 mg (2)
Sodium chloride 8.45mg (3
) l/ION sodium hydroxide appropriate amount (4
)Water total amount 1dl)H8
, 5-9.0 Experimental Example I Effect of PCD on guinea pig airway constriction reaction PGD in guinea pigs (200 μg/kg intravenous injection)
The airway constriction reaction caused by Konzetto Ressler (Kon
It was measured according to the Zett-R'6ssler) method.

Urethane (1.5 g/kg, intraperitoneal administration) for guinea pigs
The trachea was fixed in the anterior position under anesthesia, and the incised trachea was placed on a ventilator (Harvard apparatus) via a cannula.
rodentrespirator).

In addition, the side branch of the tracheal cannula was connected to an airway constriction transducer (model 7020, manufactured by Ugobasile). Air supply per time 15-7 ml, number of air supply 70 times/n+
The load pressure on the lungs was set to 10 cm 4,0, and the amount of overflowing air was recorded via a transducer.

The airway constriction response induced by intravenous administration of 200 μg/kg of PGDt was recorded for 15 minutes. The drug was suspended in a 5% gum arabic solution, and P GD was orally administered 1 hour before administration. The results are shown in the table.

Table Suppressive effect on guinea pig airway constriction reaction administration m
Suppression rate (ff1g/kg oral administration) (%) PGD,
30 89 [Effect of the invention] By using the antiallergic agent according to the present invention, P G
Allergies such as asthma caused by Dt can be prevented and treated.

Agent: Patent Attorney Iwa 1) Hiroshi

Claims (2)

[Claims] (1) Contains a compound represented by the general formula ▲ mathematical formula, chemical formula, table, etc. ▼ (in the formula, n represents an integer from 2 to 6) or a pharmacologically acceptable salt thereof as an active ingredient. An anti-allergy agent. (2) The anti-allergic agent according to claim (1), which is an anti-asthma agent.