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WO2004112791A1 - Agent therapeutique et/ou prophylactique pour maladie pulmonaire - Google Patents

Agent therapeutique et/ou prophylactique pour maladie pulmonaire Download PDF

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Publication number
WO2004112791A1
WO2004112791A1 PCT/JP2004/009209 JP2004009209W WO2004112791A1 WO 2004112791 A1 WO2004112791 A1 WO 2004112791A1 JP 2004009209 W JP2004009209 W JP 2004009209W WO 2004112791 A1 WO2004112791 A1 WO 2004112791A1
Authority
WO
WIPO (PCT)
Prior art keywords
asthma
induced asthma
lung disease
eosinophilic
induced
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2004/009209
Other languages
English (en)
Japanese (ja)
Inventor
Kimihito Sasaki
Motoya Mie
Haruhiko Manabe
Etsuo Ohshima
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
KH Neochem Co Ltd
Original Assignee
Kyowa Hakko Kogyo Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kyowa Hakko Kogyo Co Ltd filed Critical Kyowa Hakko Kogyo Co Ltd
Priority to JP2005507317A priority Critical patent/JPWO2004112791A1/ja
Publication of WO2004112791A1 publication Critical patent/WO2004112791A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • 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.
  • 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.
  • Pulmonary disease eg, antigen-induced asthma, exercise-induced asthma, cold-induced asthma, aspirin asthma, toxicant-induced asthma, etc.
  • the present invention relates to the following (1) to (18).
  • 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.
  • 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.
  • 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:
  • 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
  • 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 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
  • compound (I) 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.
  • 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.
  • 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.
  • Test example La, J, G Inhibitory effect on antigen-induced airway eosinophil infiltration
  • ovalbumin ovalbumin
  • Amber Pure Chemical Industries 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.
  • 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.
  • 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.
  • 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 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).
  • BALF bronchoalveolar lavage fluid
  • the total white blood cell count in BALF was measured using an automatic blood cell counter (Nihon Kohden ⁇ ).
  • 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.
  • 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
  • Bronchial asthma 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.
  • 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
  • GINA Asthma
  • GINA guidelines G1 ob a1 St rat e g y f or Asthma M a n a g e me n t and
  • eosinophil pneumonia is characterized by an increase in the number of eosinophils in blood, lungs, etc. [Molecular Medicine-Toudi (Mo 1 Med.
  • 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.
  • 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.
  • 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.
  • 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.
  • a sterile aqueous preparation containing the active compound which is preferably isotonic with the blood of the recipient consist of a sterile aqueous preparation containing the active compound which is preferably isotonic with the blood of the recipient.
  • 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.
  • an inhaler such as a nebulizer can be used.
  • inhalation propellant conventionally known ones can be widely used.
  • 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.
  • 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 such as methanol, ethanol, diethylene glycol and propylene glycol; dimethyl sulfoxide, dodecyl pyrrolidone and the like.
  • Polar solvents such as methanol, ethanol, diethylene glycol and propylene glycol
  • dimethyl sulfoxide 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 modifier
  • parenteral preparations are also selected from the diluents, flavors, and excipients, disintegrants, lubricants, binders, surfactants, plasticizers, preservatives, etc. exemplified for the oral preparation.
  • 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.
  • 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.
  • the dose and the number of administrations vary depending on the various conditions described above.
  • 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.
  • RT-15 type manufactured by Kikusui Co., Ltd.
  • 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).
  • 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.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne un agent thérapeutique et/ou prophylactique ou un sel pharmaceutiquement acceptable de ce dernier. Cet agent thérapeutique et/ou prophylactique, qui contient, en tant que principe actif, du 4-[(3,5-dichloro-4-pyridiyle)-carbamyl]-7-méthoxy-2-(4-méthylpiperazin-1-ylcarbonyl)-benzofurane, est représenté par la formule générale (I). Cet agent thérapeutique et/ou prophylactique convient aux maladies pulmonaires accompagnées d'une inflammation éosinophilique (par exemple, l'asthme, notamment l'asthme induit par des antigènes, l'asthme induit par l'exercice, l'asthme induit par un refroidissement, l'asthme induit par l'aspirine et l'asthme induit par détriment ; la pneumopathie chronique idiopathique à éosinophiles et la pneumopathie aiguë idiopathique à éosinophiles).
PCT/JP2004/009209 2003-06-23 2004-06-23 Agent therapeutique et/ou prophylactique pour maladie pulmonaire Ceased WO2004112791A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2005507317A JPWO2004112791A1 (ja) 2003-06-23 2004-06-23 肺疾患の治療および／または予防剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2003177772 2003-06-23
JP2003-177772 2003-06-23

Publications (1)

Publication Number Publication Date
WO2004112791A1 true WO2004112791A1 (fr) 2004-12-29

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PCT/JP2004/009209 Ceased WO2004112791A1 (fr) 2003-06-23 2004-06-23 Agent therapeutique et/ou prophylactique pour maladie pulmonaire

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JP (1) JPWO2004112791A1 (fr)
WO (1) WO2004112791A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021528107A (ja) * 2018-07-31 2021-10-21 コリア・インスティトゥート・オブ・オリエンタル・メディスン 羅漢果抽出物を有効成分として含有する呼吸器疾患の予防、改善、または治療用組成物

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06100446A (ja) * 1990-10-15 1994-04-12 Merck & Co Inc （Ｓ）−α−フルオロメチル−ヒスチジン及びそのエステルを使用するぜん息の治療方法
WO1996036624A1 (fr) * 1995-05-19 1996-11-21 Kyowa Hakko Kogyo Co., Ltd. Composes heterocycliques contenant de l'oxygene
WO1999016768A1 (fr) * 1997-10-01 1999-04-08 Kyowa Hakko Kogyo Co., Ltd. Derives de benzofuranne
JP2001516715A (ja) * 1997-09-16 2001-10-02 セプラコール， インク． 光学的に純粋な（ｓ）−サルメテロールを用いる肺障害を治療するための方法及び組成物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06100446A (ja) * 1990-10-15 1994-04-12 Merck & Co Inc （Ｓ）−α−フルオロメチル−ヒスチジン及びそのエステルを使用するぜん息の治療方法
WO1996036624A1 (fr) * 1995-05-19 1996-11-21 Kyowa Hakko Kogyo Co., Ltd. Composes heterocycliques contenant de l'oxygene
JP2001516715A (ja) * 1997-09-16 2001-10-02 セプラコール， インク． 光学的に純粋な（ｓ）−サルメテロールを用いる肺障害を治療するための方法及び組成物
WO1999016768A1 (fr) * 1997-10-01 1999-04-08 Kyowa Hakko Kogyo Co., Ltd. Derives de benzofuranne

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHUNG K.F.: "The role of new asthma treatments", ALLERGOL. INT., vol. 47, 1998, pages 237 - 246, XP002985361 *
DUPLANTIER A.J. ET AL.: "7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase", J. MED. CHEM., vol. 41, 1998, pages 2268 - 2277, XP002938447 *
IKEMURA T. ET AL.: "Type 4 phosphodiesterase inhibitors attenuate respiratory syncytial virus-induced airway hyper-responsiveness and lung eosinophilia", J. PHARMACOL. EXP. THER., vol. 294, no. 2, 2000, pages 701 - 706, XP002985362 *
MIE M. ET AL.: "Rat zensoku model ni okeru PDE4 sogaiyaku 7 nichikan renzoku toyo no koka no kento", ALLERGY, vol. 51, no. 2/3, 2002, pages 318, XP002985363 *
TEIXEIRA M.M. ET AL.: "Phosphodiesterase (PDE)4 inhibitors: anti-inflammatory drugs of the future?", TRENDS PHARMACOL. SCI., vol. 18, 2000, pages 164 - 170, XP004094497 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021528107A (ja) * 2018-07-31 2021-10-21 コリア・インスティトゥート・オブ・オリエンタル・メディスン 羅漢果抽出物を有効成分として含有する呼吸器疾患の予防、改善、または治療用組成物

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