WO2004112791A1

WO2004112791A1 - Therapeutic and/or preventive agent for lung disease

Info

Publication number: WO2004112791A1
Application number: PCT/JP2004/009209
Authority: WO
Inventors: Kimihito Sasaki; Motoya Mie; Haruhiko Manabe; Etsuo Ohshima
Original assignee: Kyowa Hakko Kogyo Co., Ltd.
Priority date: 2003-06-23
Filing date: 2004-06-23
Publication date: 2004-12-29
Also published as: JPWO2004112791A1

Abstract

A therapeutic and/or preventive agent which contains, as an active ingredient, 4-[(3,5-dichloro-4-pyridyl)carbamoyl]-7-methoxy-2-(4-methylpiperazin-1-ylcarbonyl)benzofuran, which is represented by the general formula (I): or a pharmacologically acceptable salt thereof. It is useful for lung diseases accompanied by eosinophilic inflammation (e.g., bronchial asthma such as antigen-induced asthma, exercise-induced asthma, chill-induced asthma, aspirin asthma, and detriment-induced asthma, chronic eosinophilic pneumonia, and acute eosinophilic pneumonia).

Description

. Specification

Agent for treating and / or preventing lung disease

Technical field

The present invention relates to 4-[(3,5-dichloro-4-pyridyl) caprubamoyl] -17-methoxy-1-2- (4-methylbiperazine-11-ylcarbonyl) benzofuran or a pharmaceutically acceptable salt thereof. The present invention relates to an agent for treating and / or preventing a pulmonary disease exhibiting eosinophilic inflammation, which is contained as a component.

Yutaka

In the treatment of bronchial asthma in recent years, it is important to treat not only during attacks but also when there is no attack (at remission). Drugs used during seizures (Lirino I) include tracheal dilators, and anti-inflammatory drugs are used as remedies (controllers) during remission. On the other hand, phosphodiesterase-IV (PDE-IV) inhibitors are promising as therapeutic agents for diseases such as asthma [Expert Opinion 'One Investigational' Drugs (Exp. Op in. Invest. Drugs) ), 1999, 8 volumes, p. 1301].

Conventionally, 4-[(3,5-dichloro-1-pyridyl) caprubamoyl] -17-methoxy-2- (4-methylbiperazine-11-ylcarbonyl) benzofuran or a pharmaceutically acceptable salt thereof Is known to be used as a PDE-IV inhibitor (WO 96/36624, WO 99/16768).

Disclosure of the invention

An object of the present invention is to provide 4-[(3,5-dichloro-4-pyridyl) caprubamoyl] -17-methoxy-12- (4-methylbiperazine-11-ylcarbonyl) benzofuran or a pharmacological agent thereof. Pulmonary disease (eg, antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, toxicant-induced asthma, etc.), To provide treatment and / or prophylactic agents for eosinophilic pneumonia, acute eosinophilic pneumonia, etc.).

The present invention relates to the following (1) to (18).

(1) General formula (I)

(I)

4 — [(3,5-Dichloro-1-41-pyridyl) pothambamoyl] -17-Methoxy-1-2- (4-methylpiperazine-1-ylcarbonyl) benzofuran or a 'pharmaceutically acceptable salt thereof A therapeutic and / or prophylactic agent for pulmonary disease presenting eosinophilic inflammation, comprising as an active ingredient.

(2) The therapeutic and / or prophylactic agent for pulmonary disease according to (1), wherein the pulmonary disease presenting eosinophilic inflammation is bronchial asthma or eosinophilic pneumonia.

(3) Pulmonary disease presenting eosinophilic inflammation consists of antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, toxic substance-induced asthma, chronic eosinophilic pneumonia and acute eosinophilic pneumonia The therapeutic and / or prophylactic agent for lung disease according to (1), which is a lung disease selected from the group.

(4) The therapeutic and / or prophylactic agent for pulmonary disease according to (1), wherein the pulmonary disease presenting with eosinophilic inflammation is bronchial asthma. .

(5) The lung disease exhibiting eosinophilic inflammation is a lung disease selected from the group consisting of antigen-induced asthma, rush-induced asthma, cold-induced asthma, aspirin asthma and toxic substance-induced asthma.

(1) The treatment and Z or prophylactic agent for pulmonary disease according to the above.

(6) The therapeutic and / or prophylactic agent for pulmonary disease according to any one of (1) to (5), which is an inhalant.

(7) General formula (e)

(I)

4- [(3,5-dichrolic 4-pyridyl) pothambyl] -7-methoxy-2- (4-methylbiperazine-11-ylcarbonyl) benzofuran represented by the formula or a pharmaceutically acceptable salt thereof A method for treating and / or preventing a lung disease exhibiting eosinophilic inflammation, which comprises administering an effective amount of

(8) The method for treating and / or preventing lung disease according to (7), wherein the lung disease presenting eosinophilic inflammation is bronchial asthma or eosinophilic pneumonia.

(9). Pulmonary diseases presenting eosinophilic inflammation include antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, harmful substance-induced asthma, chronic eosinophilic pneumonia and acute eosinophilic pneumonia. The method for treating and preventing or preventing lung disease according to (7), which is a lung disease selected from the group consisting of:

(10) The method for treating and / or preventing lung disease according to (7), wherein the lung disease presenting eosinophilic inflammation is bronchial asthma.

(11) The lung disease exhibiting eosinophilic inflammation is a lung disease selected from the group consisting of antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, and harmful substance-induced asthma

(7) The method for treating lung disease and Z or * prevention according to the above.

(12) The method for treating and preventing or preventing lung disease according to any one of (7) to (11), wherein the administration is inhalation administration.

(13) A general formula (I) for producing a therapeutic and / or prophylactic agent for a pulmonary disease exhibiting eosinophilic inflammation

(I)

Use of 4-[(3,5-dichloro-4-pyridyl) pothambamoyl] -7-methoxy-2- (4-methylbiperazine-11-ylcarbonyl) benzofuran or its pharmaceutically acceptable salt represented by .

(14) The use according to 13), wherein the lung disease presenting eosinophilic inflammation is bronchial asthma or eosinophilic pneumonia.

(15) Pulmonary diseases presenting eosinophilic inflammation consist of antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, toxicant-induced asthma, chronic eosinophilic pneumonia and acute eosinophilic pneumonia The use according to (13), which is a lung disease selected from the group.

(16) The use according to (13), wherein the pulmonary disease exhibiting eosinophilic inflammation is bronchial asthma.

(17) The lung disease exhibiting eosinophilic inflammation is a lung disease selected from the group consisting of antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, and harmful substance-induced asthma

(13) Use as described.

(18) The use according to any one of (13) to (17), wherein the therapeutic or Z or prophylactic agent for pulmonary disease presenting eosinophilic inflammation is an inhalant.

Hereinafter, the compound represented by the general formula (I) is referred to as compound (I).

Pharmaceutically acceptable salts of compound (I) include pharmacologically acceptable acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts and the like. , Pharmacologically acceptable acid addition salts of compound (I) include inorganic salts such as hydrochloride, sulfate, nitrate, phosphate, acetate, maleate, fumarate, and citrate Organic salts such as salts; and pharmacologically acceptable metal salts include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt and calcium salt; Aluminum salts, zinc salts, etc., and pharmacologically acceptable ammonium salts include salts such as ammonium salts and tetramethylammonium salts. Examples of the physiologically acceptable organic amine addition salts include addition salts such as morpholine and piperidine, and examples of the pharmacologically acceptable amino acid addition salts include glycine, phenylalanine, lysine, and aspartic acid. Addition salts such as glutamic acid are mentioned. Next, a method for producing the compound (I) will be described.

Compound (I) can be produced by the method described in WO 96/36624 or WO 99/16768.

Compound (I) may have stereoisomers such as tautomers, and the therapeutic and / or preventive agent for pulmonary disease presenting eosinophilic inflammation of the present invention includes all of these, including these. Possible isomers and their mixtures can be used.

When it is desired to obtain a salt of compound (I), if compound (I) is obtained in the form of a salt, purification may be carried out as it is. What is necessary is just to dissolve or suspend in a solvent, add an acid or a base, and isolate and purify.

Compound (I) and its pharmacologically acceptable salts may exist in the form of adducts with water or various solvents, and these adducts also cause the eosinophilic inflammation of the present invention. It can be used as a therapeutic and / or prophylactic agent for the presenting lung disease.

Next, the pharmacological action of compound (I) will be described with reference to test examples.

Test example: La, J, G Inhibitory effect on antigen-induced airway eosinophil infiltration

The following tests were performed using the known method [Palmanary '

(Pulmonary Phaririacology), 1995, Vol. 8, p. 83. '

Six-week-old male BN rats (Charles River Japan) were used for the experiment. The lights are housed in a breeding room with a room temperature of 19-25 ° C, humidity of 3'0-70%, and 12 hours of lighting (7 am-7 pm). They were fed with commercially available solid feed and water ad libitum.

1 mg of ovalbumin (OVA, manufactured by Sigma) and 10 Omg of aluminum hydroxide (manufactured by Wako Pure Chemical Industries) suspended in 1 mL of physiological saline (Otsuka Pharmaceutical Factory) were added subcutaneously to the plate. after administration, killed Bordetella pertussis suspension 0. 5mL (2 x 10 ¹ ° pieces 1 mL saline, manufactured by Wako Pure Chemical Industries, Ltd.) were actively sensitized by intraperitoneally. 14 days after active sensitization, put a light in a plastic chamber (30x50x30cm), 1 Antigen exposure was performed by inhaling physiological saline at a weight / volume% of OVA for 30 minutes. An ultrasonic nebulizer (Omron) was used for inhalation. According to a conventional method, the compound (I) is suspended in 0.125% by weight / vol% tyloxapol (Arevel: registered) ^ mark, manufactured by Azur Corporation so that the concentration of the compound (I) becomes 5 mg / mL, and the compound (I) is suspended. A suspension for administration of I) was prepared. At 60 minutes before the antigen exposure, the administration solvent (0.125 wt.% Z volume% tioxaxole) or the suspension for administration of the compound (I) was placed in the left and right bronchi of the rats, 100 bronchi and 20 bronchi in total. Was administered internally.

A group in which a suspension for administration of the compound (I) was intrabronchially administered to the sensitized rats, and a physiological diet containing 1% (w / v) OVA was inhaled was treated with the compound (I) -added group. Intrabronchial administration of 1 wt% volumetric saline 0 VA inhaled saline was administered to the group treated with solvent, and sensitized rats were administered bronchial administration of the administered solvent intrabronchially and only saline was inhaled. The group was a physiological saline solution group. '

Bronchoalveolar lavage (BAL) was performed 24 hours after antigen exposure. That is, the rat was anesthetized, and the alveolar cavity was washed with a physiological saline solution via a tracheal force neura to obtain a bronchoalveolar lavage fluid (BALF).

The total white blood cell count in BALF was measured using an automatic blood cell counter (Nihon Kohden ^). In addition, a smear of cells was prepared, stained with Giemsa, observed under an optical microscope, and the number of eosinophil cells was counted to calculate the ratio. The eosinophil count was calculated by multiplying the total leukocyte count by the eosinophil cell count ratio. The inhibition rate (%) against the increase in the number of eosinophils in BALF was calculated according to the following.

Number of eosinophils in solvent-administered group-Number of eosinophils in compound (I) -added group

Inhibition rate (%) = X 100 number of eosinophils in vehicle-administered group / number of eosinophils in physiological saline group

Table 1 shows the results. In addition, each value of the eosinophil count is shown by the standard error of the mean value. Treatment group Dose Eosinophil count suppression rate

(g / animal) (IOVBALF) (%) Saline 0

Solvent 0.9 ± 0.2 ^A

Compound (I) 1000 0.2 ± 0.1 86

*: P <0.001 compared with saline group, Aspin-Welch test) * ■ P <0.05 (Comparison with solvent group, Steel test) The results of the above test show that administration of compound (I) suppresses eosinophil infiltration into the lung.

Bronchial asthma, on the other hand, is a disease characterized by eosinophilic airway inflammation [Clinical-Experimental Allergy (Cl in. Exp. All.) 2002, 32 volumes, p: 162], It is known that marked eosinophil infiltration into lung tissue and BALF is observed in this disease. In addition, non-steroidal anti-inflammatory drugs such as aspirin, harmful substances such as diesel exhaust, antigens, exercise, and cold air are considered to be factors that induce or exacerbate symptoms such as inflammation in asthma [Global Initiative] G 1 oba 1 Init iat ive f or

Asthma (GINA)), GINA guidelines (G1 ob a1 St rat e g y f or Asthma M a n a g e me n t and

Prevention) _N 2002, p. 39].

Furthermore, it is known that eosinophil pneumonia is characterized by an increase in the number of eosinophils in blood, lungs, etc. [Molecular Medicine-Toudi (Mo 1 Med.

Today), 2000, vol. 6, p. 20].

Based on the above, compound (I) or a pharmacologically acceptable salt thereof includes, for example, bronchial asthma such as antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, and harmful substance-induced asthma, It is considered to be effective as a therapeutic and / or prophylactic agent for pulmonary diseases exhibiting eosinophilic inflammation such as atopic pneumonia and acute eosinophilic pneumonia.

Compound (I) or a pharmacologically acceptable salt thereof can be administered alone as it is, but it is usually desirable to provide it as various pharmaceutical preparations. These pharmaceutical preparations are used for animals and humans.

The pharmaceutical preparation according to the present invention can contain Compound (I) or a pharmacologically acceptable salt thereof alone or as a mixture with any other active ingredient for treatment as an active ingredient. . In addition, such pharmaceutical preparations are produced by mixing the active ingredient with one or more pharmacologically acceptable carriers and by any method well known in the technical field of pharmaceuticals.

As the administration route, it is desirable to use the most effective one for treatment, and it can be oral or parenteral such as intravenous, intratracheal, or transdermal. Examples of the administration form include tablets, injections, inhalants, and external preparations. Sustained release indications are also available.

Suitable for oral administration, for example, tablets are excipients such as lactose and mannitol, disintegrants such as starch, lubricants such as magnesium stearate, binders such as hydroxypropylcellulose, and interfaces such as fatty acid esters. It can be produced using an activator, a plasticizer such as glycerin, or a preservative such as benzoic acid or P-hydroxybenzoic acid esters.

Suitable for parenteral administration, eg injection, consist of a sterile aqueous preparation containing the active compound which is preferably isotonic with the blood of the recipient. For example, a solution for injection can be prepared using a carrier such as a salt solution, a glucose solution, or a mixture of water and a glucose solution. Inhalants are prepared by making the active ingredient into a powder or liquid form, blending it into an inhalation propellant or carrier, and filling it in an appropriate inhalation container such as a metered dose inhaler or dry powder inhaler. When the active ingredient is a powder, a conventional mechanical powder inhaler can be used, and when the active ingredient is a liquid, an inhaler such as a nebulizer can be used. As the inhalation propellant, conventionally known ones can be widely used. For example, CFC-11, CFC-12, CFC-12, CFC-12, CFC-11, CFC-11 4, 1-fluorocarbons, 1-fluorocarbons, 1-fluorocarbons, 1-fluorocarbons, 1-fluorocarbons, etc. Gas, HFC-227, HFA-134a and other alternative chlorofluorocarbons, propane, isobutane, n-butane and other hydrocarbon gases, getyl ether ', nitrogen gas, carbon dioxide gas, etc. . As the carrier, conventionally known carriers can be widely used, and examples thereof include sugars, sugar alcohols, and amino acids, and lactose and D-mannitol are preferred.

The dosage form suitable for the external preparation is not particularly limited, and the active ingredient is dissolved or mixed and dispersed in the base to form a cream, paste, jelly, gel, emulsion, liquid, or the like. What is done (ointment, liniment, lotion, etc.), base or active ingredient and percutaneous absorption enhancer dissolved or mixed and dispersed in, for example, polyethylene, polyester, polyethylene terephthalate, etc. Products spread on top (such as cataplasms, tapes, etc.). As the base, any pharmacologically acceptable base may be used. Conventionally known bases such as ointments, liniments, lotions and the like can be used, for example, sodium alginate; gelatin, Koichi Starch, tragacanth gum, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, xanthan gum, dextrin, carboxymethylstarch, polyvinyl alcohol, sodium polyacrylate, methoxyethylene-maleic anhydride copolymer, polyvinylether, polyvinylpyrrolidone Oils such as beeswax, olive oil, cocoa oil, sesame oil, soybean oil, bakaki oil, laccase oil, beef oil, pork oil, lanolin; oils and fats such as white serine, yellow serine; paraffin; Carbon gel ointment (for example, Plastibase, manufactured by Taisho Pharmaceutical Co., Ltd.); higher fatty acids such as stearic acid; higher alcohols such as cetyl alcohol and stearyl alcohol; polyethylene Glycol; and water, and the like. The above-mentioned percutaneous absorption enhancer may be any pharmacologically acceptable agent, for example, alcohols such as methanol, ethanol, diethylene glycol and propylene glycol; dimethyl sulfoxide, dodecyl pyrrolidone and the like. Polar solvents; urea; esters such as ethyl laurate, isopropyl myristate, and cetyl octanoate; azones; If necessary, inorganic fillers such as kaolin, bentonite, zinc oxide and titanium oxide; viscosity modifiers; antioxidants; pH regulators; humectants such as glycerin and propylene glycol may be added. Good.

In addition, these parenteral preparations are also selected from the diluents, flavors, and excipients, disintegrants, lubricants, binders, surfactants, plasticizers, preservatives, etc. exemplified for the oral preparation. One or more auxiliary components can also be added. '

The dose and frequency of compound (I) or a pharmacologically acceptable salt thereof will vary depending on the mode of administration, age and weight of the patient, and the nature or severity of the condition to be treated. 0.0 lmg per adult: L g, preferably 0.05 to 50 mg, is administered once or several times a day. In the case of parenteral administration such as intravenous administration, 0.001 to 10 Omg, preferably 0.01 to 5 Omg per adult is administered once or several times a day. For intratracheal administration (inhalation), 0.001 mg to lg, preferably 0.01 to: L 00 mg, more preferably 0.5 mg to 2 Omg once a day per adult Dosing once. However, the dose and the number of administrations vary depending on the various conditions described above.

Hereinafter, embodiments of the present invention will be described with reference to examples. BEST MODE FOR CARRYING OUT THE INVENTION

Example 1: Tablet

A tablet having the following composition is prepared by a conventional method. 40 g of compound (I), 286.8 g of lactose and 60 g of potato starch are mixed, and 120 g of a 10% aqueous solution of hydroxypropyl cell mouth is added thereto. The mixture is kneaded by a conventional method, granulated and dried, and then sized to obtain granules for tableting. 1.2 g of magnesium stearate was mixed with the calorie, and the mixture was compressed with a tablet machine (RT-15 type, manufactured by Kikusui Co., Ltd.) equipped with an 8 mm-diameter punch. Is obtained.

Prescription compound (I) 20 mg

Lactose143 4 mg

30 mg

Hydroxypropyl cellulose 6 mg

Magnesium stearate 0 6 mg.

200 mg

Example 2: Injection

An injection having the following composition is prepared by a conventional method. 1 g of Compound (I) and 5 g of D-mannitol are added to and mixed with distilled water for injection, and the pH is adjusted to 6 by adding an aqueous solution of hydrochloric acid and an aqueous solution of sodium hydroxide. Make the total volume 1000 mL. The obtained mixture is aseptically filled into glass vials in an amount of 2 mL each to give an injection (containing 2 mg of active ingredient per vial).

Prescription compound (I) 2 mg

D—mannitol 0 mg

Hydrochloric acid aqueous solution

Sodium hydroxide aqueous solution

Distilled water for injection

2.00 mL

Example 3: Dry powder inhalant

10 g of compound (I) was prepared using a jet mill (A-O JET; Seishin Enterprise). Grind with air pressure SkgZcm ² at a feed rate of 1.5 minutes. The resulting ground compound (I) and lactose (Pharmatose 325M; manufactured by DMV) are mixed at a weight ratio of 1: 5 to obtain a dry powder preparation.

Formulation Compound (I) 16.7 mg

'M: 83.3 mg

100 mg

Τ Noh 'I, cow

According to the present invention, 4-[(3,5-dichloro-4-pyridyl) caprubamoyl] 7-methoxy-12- (4-methylbiperazine-11-ylcarbonyl) benzofuran or a pharmaceutically acceptable salt thereof is used as an active ingredient. Pulmonary diseases presenting with eosinophilic inflammation (eg, bronchial asthma such as antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, toxicant-induced asthma, chronic eosinophilic pneumonia, acute And / or a prophylactic and / or prophylactic agent for acidophilic pneumonia).

Claims

1. General formula (I)

Mouth I)

4 — [(3,5-dichloro-4-pyridyl) caprubamoyl] -17-methoxy-2--2- (4-methylbiperazine-11-ylcarbonyl) benzofuran or a pharmaceutically acceptable salt thereof An agent for treating and / or preventing a pulmonary disease exhibiting eosinophilic inflammation, which is contained as an active ingredient. '

Enclosure

2. The therapeutic and / or Z-prophylactic agent for pulmonary disease according to claim 1, wherein the pulmonary disease presenting eosinophilic inflammation is bronchial asthma or eosinophilic pneumonia.

3. Pulmonary diseases presenting eosinophilic inflammation include antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, harmful substance-induced asthma, chronic eosinophilic pneumonia and acute eosinophilic pneumonia 2. The therapeutic and / or prophylactic agent for a lung disease according to claim 1, which is a lung disease selected from the group consisting of:

4. The therapeutic and / or prophylactic agent for pulmonary disease according to claim 1, wherein the pulmonary disease presenting eosinophilic inflammation is bronchial asthma.

5. The lung disease exhibiting eosinophilic inflammation is a lung disease selected from the group consisting of antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma and toxic substance-induced asthma. The therapeutic and / or prophylactic agent for the pulmonary disease according to the above.

6. The therapeutic and / or prophylactic agent for pulmonary disease according to any one of claims 1 to 5, which is an inhalant. '

7. General formula (I)

(I)

4-[(3,5-dichloro-1-b-ridyl))-rubamoyl] -7-methoxy-2- (4-methylbiperazine-1-ylcarbonyl) benzofuran represented by the formula: or a pharmaceutically acceptable salt thereof For treating and / or preventing lung disease exhibiting eosinophilic inflammation, characterized by administering an effective amount of

8. The method for treating and / or preventing a lung disease according to claim 7, wherein the lung disease presenting eosinophilic inflammation is bronchial asthma or eosinophilic pneumonia.

9. Pulmonary diseases presenting with eosinophilic inflammation include antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, toxicant-induced asthma, chronic eosinophilic pneumonia and acute eosinophilic pneumonia. The method for treating and / or preventing lung disease according to claim 7, which is a lung disease selected from the group consisting of:

10. The method for treating and / or preventing lung disease according to claim 7, wherein the lung disease presenting eosinophilic inflammation is bronchial asthma. '

1 1. The lung disease exhibiting eosinophilic inflammation is a lung disease selected from the group consisting of antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma and toxic substance-induced asthma. 7. The method for treating and / or preventing a lung disease according to claim 7.

12. The method for treating and / or preventing a pulmonary disease according to any one of claims 7 to 11, wherein the administration is inhalation administration.

13. General formula (I) for the treatment of pulmonary disease with eosinophilic inflammation and for the manufacture of Z or prophylactic agent

(I)

The use of 4-[(3,5-dichloro-1-pyridyl) pothambamoyl] -17-methoxy-2- (4-methylbiperazine-1-ylcarbonyl) pentozofran or a pharmaceutically acceptable salt thereof represented by the formula:

14. The use according to claim 13, wherein the lung disease exhibiting eosinophilic inflammation is bronchial asthma or eosinophilic pneumonia. , '

1 5. Lung diseases presenting eosinophilic inflammation consist of antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, toxicant-induced asthma, chronic eosinophilic pneumonia and acute eosinophilic pneumonia. The use according to claim 13, which is a lung disease selected from the group.

16. The use according to claim 13, wherein the lung disease exhibiting eosinophilic inflammation is bronchial asthma.

17. Claims in which the lung disease exhibiting eosinophilic inflammation is a lung disease selected from the group consisting of antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma and toxic substance-induced asthma. Use according to clause 3.

18. The use according to any one of claims 13 to 17, wherein the therapeutic and / or Z-prophylactic agent for pulmonary disease presenting eosinophilic inflammation is an inhalant.