WO2009090976A1 - Préparation thérapeutique transmucosale pour une obstruction nasale - Google Patents

Préparation thérapeutique transmucosale pour une obstruction nasale Download PDF

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Publication number
WO2009090976A1
WO2009090976A1 PCT/JP2009/050421 JP2009050421W WO2009090976A1 WO 2009090976 A1 WO2009090976 A1 WO 2009090976A1 JP 2009050421 W JP2009050421 W JP 2009050421W WO 2009090976 A1 WO2009090976 A1 WO 2009090976A1
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Prior art keywords
nasal
preparation
transmucosal
transmucosal preparation
mucosa
Prior art date
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PCT/JP2009/050421
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English (en)
Japanese (ja)
Inventor
Masakazu Ishimura
Masahiro Suda
Sayuri Kataoka
Toshiaki Okuda
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Kaken Pharmaceutical Co., Ltd.
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Publication of WO2009090976A1 publication Critical patent/WO2009090976A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/24—Radicals substituted by oxygen atoms
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to 2- ⁇ N- [4- (4-chlorobenzenesulfonyl), which exhibits an inhibitory effect on nasal congestion (nasal congestion) among nasal inflammation caused by cold, hay fever, hay fever, allergic rhinitis and the like.
  • the present invention relates to a preparation for administration, particularly to a transmucosal preparation for treatment of nasal atresia that exhibits immediate action.
  • sneezing is a reflex movement that instantly expels foreign matter by releasing expiratory air, followed by an increase in secretory glands Mucus secretion occurs and physically removes invading foreign bodies. Furthermore, due to increased vascular permeability and infiltration of eosinophils into tissues, a biological reaction that removes infection and allergens at the cellular level occurs, forming an inflammatory pathology, resulting in swelling of the nasal mucosa, mainly in the lower turbinates Occurs and a decrease in nasal air permeability due to stenosis, ie nasal congestion, appears. This nasal congestion lasts for several hours to a day.
  • nasal obstruction obstructs nasal breathing for a long time, so that concentration and attention are distracted, and it also interferes with nighttime sleep, reducing the quality of daily life (QOL: Quality of Life).
  • QOL Quality of Life
  • mouth breathing can cause dryness and pain in the throat, and coughing can be caused by foreign objects entering the airways. Therefore, the reduction / removal of nasal inflammation is an important therapeutic point.
  • Drugs used to treat allergic rhinitis include chemical mediator release inhibitors such as sodium cromoglycate, tranilast, amlexanox, and pemirolast potassium; d-chlorpheniramine maleate, clemastine fumarate, ketotifen fumarate Acid salt, azelastine hydrochloride, oxatomide, mequitazine, emedastine fumarate, epinastine hydrochloride, ebastine, cetirizine hydrochloride, levocabastine hydrochloride, bepotastine besylate, fexofenadine hydrochloride, olopatadine hydrochloride, loratadine histamine H 1 receptor antagonists, such as; pranlukast hydrate, leukotriene receptor antagonists, such as montelukast sodium; prostaglandin D 2 ⁇ thromboxane a 2 receptor antagonists such as ramatroban; Th2
  • leukotriene receptor antagonists In patients with perennial allergic rhinitis and strong nasal congestion, leukotriene receptor antagonists, prostaglandin D 2 / thromboxane A 2 receptor antagonists and nasal spray steroids alone, or leukotriene receptor antagonists or Treatment using a prostaglandin D 2 / thromboxane A 2 receptor antagonist in combination with a nasal spray steroid has been performed. In cases of hay fever and strong nasal congestion, leukotriene receptor antagonists or prostaglandin D 2 / thromboxane A 2 receptor antagonists are used for initial therapy. Treatments that combine nasal vasoconstrictors, nasal spray steroids, leukotriene receptor antagonists, and antihistamines have been performed (Non-Patent Documents 1 and 2).
  • Non-patent Documents 1 and 2 show that Non-Patent Document 2 is published after the date of filing of the present application, and is not a prior art document for the present application, but merely shows the transition of technology in this technical field after the filing date of the present application. Is.
  • KP-496 2- ⁇ N- [4- (4-chlorobenzenesulfonylamino) butyl] -N- ⁇ 3-[(4-isopropyl-2-thiazolyl) methoxy] benzyl ⁇ sulfamoylbenzoic acid (hereinafter abbreviated as KP-496). sometimes it is) is leukotriene D 4 receptor combines the antagonism and thromboxane a 2 receptor antagonism, are useful in the treatment of asthma and chronic inflammatory pulmonary disease (Patent documents 1 and 2).
  • the present invention provides an immediate improvement of nasal obstruction for nasal obstruction symptoms that are therapeutic points as described above among nasal inflammation symptoms caused by cold, hay fever, hay fever, allergic rhinitis, etc. It is an object of the present invention to provide a transmucosal preparation for treating nasal atrophy having an action.
  • the present inventors have contributed to the onset of nasal obstruction reaction by cysteinyl leukotriene and thromboxane A 2, so that the point of KP-496 having an antagonistic action on the receptors of both substances. Nasal administration was studied. As a result, compared with conventional leukotriene receptor antagonists, the nasal preparation of KP-496 exhibits an excellent effect of promptly reducing and eliminating nasal congestion caused by inflammatory lesions of the nasal mucosa. I found it.
  • the present invention which is a means for solving the above problems is as follows (1) to (10).
  • a transmucosal preparation for the treatment of nasal atresia containing a possible salt as active ingredient (2) The transmucosal preparation for treating nasal atrophy according to the above (1), wherein the mucosa is a nasal mucosa or ocular mucosa; (3) The transmucosal preparation for treating nasal atrophy according to (1) or (2) above, wherein the mucosa is a nasal mucosa; (4) The transmucosal administration preparation for treating nasal atrophy according to any one of (1) to (3) above, in order to immediately reduce or eliminate nasal congestion symptoms; (5) The
  • KP-496 which is an active ingredient of the transmucosal preparation for the treatment of nasal congestion of the present invention, is dosed against the delayed nasal obstruction reaction in the guinea pig allergic rhinitis model.
  • Dependent inhibitory action was shown.
  • KP-496 suppresses the increase in vascular permeability induced immediately after transmucosal administration in a guinea pig conjunctival vascular permeability enhancement reaction model, and unlike conventional oral leukotriene receptor antagonists, KP-496 administered transmucosally.
  • KP-496 administered transmucosally.
  • KP-496 used as an active ingredient in the transmucosal preparation for treatment of nasal atrophy according to the present invention can be produced by a chemical synthesis method described in International Publication No. 98/57935 pamphlet.
  • the pharmaceutically acceptable salt of KP-496 include metal salts such as sodium, potassium, magnesium and calcium, trimethylamine, triethylamine, pyridine, picoline, N-methylpyrrolidine, N-methylpiperidine, N- An organic salt such as methylmorpholine can be mentioned.
  • KP-496 or a pharmaceutically acceptable salt thereof may be a solvate such as a hydrate.
  • the transmucosal preparation for treatment of nasal congestion of the present invention can be produced as a solution or suspension by a conventional method. Moreover, it can be triturated with an appropriate excipient such as lactose to form a powder preparation.
  • purified water, ethanol, ethylene glycol, propylene glycol, a mixture thereof, or the like can be used as a base.
  • bases include KP-496 or a pharmaceutically acceptable salt thereof, and if necessary, a pH adjuster, a buffer, an isotonic agent, a suspending agent, a preservative (preservative), and a stabilization.
  • An agent, a solubilizing agent, a cooling agent, etc. may be added and dissolved or suspended so as to obtain a predetermined concentration.
  • As the pH adjuster sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, hydrochloric acid, sulfuric acid and the like are used.
  • pH adjusters such as sodium hydrogen phosphate, sodium dihydrogen phosphate, disodium phosphate, boric acid, borax, sodium carbonate, sodium L-glutamate, citric acid, etc.
  • the pH of the dissolution agent or suspension for nasal mucosa or ocular mucosa administration is preferably 5 to 8, more preferably 5 to 7, and even more preferably 5 to 6.
  • the osmotic pressure is preferably isotonic, and is preferably adjusted to be isotonic using an isotonic agent such as glycerin, sodium chloride, mannitol, glucose and the like.
  • the transmucosal administration preparation for treatment of nasal atrophy according to the present invention is in the form of the above-mentioned solution or suspension, 0.003% to 3% (w) of KP-496 or a pharmaceutically acceptable salt thereof is used. / V), preferably 0.01% to 2% (w / v), more preferably 0.03% to 1% (w / v).
  • Examples of the stabilizer used in the solution or suspension include sodium sulfite, sodium bisulfite, sodium metabisulfite, sodium thiosulfate, Rongalite, thioglycerol, thioglycolic acid, thiolactic acid, thioacetic acid, cysteine, and methionine.
  • Sulfur compounds such as glutathione, thiosorbitol, thioglucose, thiourea, or inorganic acids such as boric acid, borax, phosphoric acid, metaphosphoric acid, sodium carbonate, sodium bicarbonate, and salts thereof, or formic acid, oxalic acid , Organic acids such as tartaric acid, citric acid, edetic acid and their salts, or acid amides such as acetamide, diethylacetamide, nicotinic acid amide, urea, barbital, or glycol, propylene glycol, glycerin, polyethylene glycol Polyhydric alcohols and sugars such as glucose and ascorbic acid, phenols such as phenol, thymol, quinone, coumarone, and isocoumarone, or amino acids and proteins such as dibutylhydroxytoluene, glycine, glutamic acid, lysine, phenylalanine, casein, and
  • preservatives examples include paraoxybenzoates such as propyl paraoxybenzoate and butyl paraoxybenzoate, or parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, or benzalkco chloride.
  • Inverse soaps such as nium, benzethonium chloride, chlorhexidine gluconate, cetylpyridium chloride, or alcohol derivatives such as chlorobutanol, phenylethyl alcohol, benzyl alcohol, or sodium dehydroacetate, sorbic acid, sodium sorbate, etc.
  • Organic acids and their salts or phenols such as parachloromethoxyphenol and parachlormethcresol, or thimerosal, phenolmercuric nitrate, phenylmercuric borate, acetic acid Eniru mercury, organic mercurials such Nitoromezoru, or the like polymyxin B sulfate is used.
  • solubilizer for example, polyvinylpyrrolidone, polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, triethanolamine, sodium carbonate, sodium citrate and the like are used.
  • the refreshing agent for example, 1-menthol, dl-camphor and the like are used.
  • the transmucosal administration preparation for treating nasal acupuncture as a powder preparation, for example, in a solution in which an excipient is dissolved in purified water, ethanol, ethylene glycol, propylene glycol or a mixture thereof, KP- 496 or a pharmaceutically acceptable salt thereof can be mixed and spray dried to obtain a powder.
  • excipient examples include sugars such as hydroxypropylmethylcellulose, hydroxypropylcellulose, xylitol, fructose, sorbitol, lactose, inositol, sucrose, mannitol; starches such as corn starch, wheat starch, potato starch; magnesium carbonate, chloride Examples thereof include inorganic substances such as sodium and calcium sulfate. Further, if necessary, lubricants such as magnesium stearate, stearic acid, talc, etc., preservatives (preservatives), stabilizers, cooling agents, etc. used in the solution or suspension can be used. .
  • sugars such as hydroxypropylmethylcellulose, hydroxypropylcellulose, xylitol, fructose, sorbitol, lactose, inositol, sucrose, mannitol
  • starches such as corn starch, wheat starch, potato starch
  • magnesium carbonate examples thereof include inorganic substances such
  • the transmucosal administration preparation for the treatment of nasal congestion of the present invention is in the form of the powder preparation described above, 0.01% to 30% (w / w) of KP-496 or a pharmaceutically acceptable salt thereof is contained. It is preferably contained at a concentration, particularly preferably 0.03% to 20% (w / w), especially 0.1% to 10% (w / w).
  • the transmucosal preparation for the treatment of nasal disease comprising the active ingredient KP-496 of the present invention or a pharmaceutically acceptable salt thereof has a nasal inflammation state caused by cold, hay fever, hay fever, allergic rhinitis and the like. Among them, it shows an inhibitory effect on nasal congestion (nasal congestion) symptoms. In particular, it has the feature of producing an effect immediately. In particular, it has the effect of suppressing delayed nasal congestion of allergic rhinitis and suppressing the increase in nasal mucosal vascular permeability.
  • the transmucosal preparation for treatment of nasal acupuncture according to the present invention is divided into 1 to several times a day using a commonly used device for nasal mucosa administration or ocular mucosa administration device as a solution, suspension or powder.
  • Nasal mucosa or ocular mucosa can be administered.
  • the dose and the number of doses can be appropriately increased or decreased according to age, weight and symptoms.
  • concentration of an active ingredient per adult is 0.003 to 3% (w / v) in the form of a solution or suspension.
  • a preparation once to three times a day, more preferably a preparation in the form of a solution or suspension in which the concentration of the active ingredient is 0.03-1% (w / v). It is preferable to administer once or twice a day.
  • the preparation in the form of a solution or suspension contains the active ingredient 1 to 3 times a day in an amount of the active ingredient of 0.0001 to 0.3 mg / kg / day, preferably 1 to 2 times a day.
  • the patient may be administered in an amount of 0.001 to 0.07 mg / kg / day.
  • a powder preparation when administered, for example, in the nasal mucosa, a capsule containing the powder preparation is set in a small sprayer (Pubizer (registered trademark)), a hole is made in the capsule, and a nozzle is inserted into the nostril.
  • the powder preparation may be sprayed into the nasal cavity by holding a rubber ball while inhaling through the nose.
  • the powder formulation is from 0.001 to 0.3 mg / kg / day, in an amount of active ingredient 1 to 3 times a day, preferably 1 to 2 times a day, preferably 0.001 to 0.07 mg / kg. / Day in a dose.
  • transmucosal preparation for treatment of nasal congestion of the present invention includes oral and nasal antihistamines, oral and nasal antiallergic agents, oral and nasal steroids, nasal vasoconstrictors, etc. It is also possible to use together in any combination.
  • Example 1 A preparation having the following formulation was prepared as a preparation in the form of a solution containing KP-496 using a conventional method. Formulation:
  • Example 2 Inhibitory effect of KP-496 on delayed nasal obstruction in a guinea pig allergic rhinitis model
  • a preparation in the form of a solution containing KP-496 was prepared as follows. An appropriate amount of KP-496 was weighed, and 2.8-fold molar amount of 1 mol / L sodium hydroxide (hereinafter referred to as NaOH) of KP-496 was added to dissolve KP-496. After dissolution, this solution was transferred to a beaker, and Japanese Pharmacopoeia physiological saline (hereinafter referred to as physiological saline) of about 3/4 of the final preparation volume was added.
  • physiological saline Japanese Pharmacopoeia physiological saline
  • HCl 1 mol / L hydrochloric acid
  • 0.1 mol / L HCl 1 mol / L hydrochloric acid
  • physiological saline was added to make a predetermined volume.
  • the solution was filtered through a membrane filter (0.22 ⁇ m) to obtain a 0.3% KP-496 preparation.
  • a preparation medium not containing KP-496 was prepared.
  • the 0.003-0.03% KP-496 formulation was prepared by serial dilution of 0.3% KP-496 formulation with formulation media. KP-496 formulation (0.003-0.03%) and its vehicle were used as nasal test drug and nasal vehicle.
  • the content of one capsule of ONON (registered trademark) (containing 112.5 mg of pranlukast hydrate in one capsule) was finely ground in an agate mortar and then used as an oral medium. % Methylcellulose was added to prepare a 3 mg / mL pranlukast suspension.
  • ovalbumin physiological saline solution was intraperitoneally administered (initial sensitization). Two more days later, 0.2% ovalbumin physiological saline solution was injected into 0.5 mL of guinea pigs. It was administered internally. 17, 19, 22, 26, 31, 36 and 41 days after the first sensitization, 0.1, 0.2, 0.4, 0.8, 1.0, 2.0 and 4.0% ovalbumin, respectively.
  • the physiological saline solution was administered nasally into each nasal cavity of guinea pigs in an amount of 20 ⁇ L to prepare an allergic rhinitis model.
  • the test group was divided into a control group (Group A), a test drug group 3 (Groups B, C and D), and a control drug group 1 (Group E).
  • the results are shown in FIGS. KP-496 was used as the test drug and pranlukast hydrate was used as the control drug.
  • the test drug, control drug and vehicle were administered 1 hour before and 2 hours after nasal administration of 4.0% ovalbumin physiological saline solution.
  • a nasal medium and an oral medium were respectively administered, and in the test drug group, the test drug was administered nasally and an oral medium was administered.
  • the nasal medium was administered and the control drug was orally administered.
  • the increase in nasal resistance value is a dose-dependent low value in the test drug group (groups B, C, and D), and the test drug can significantly reduce the nasal obstruction reaction. It became clear.
  • Example 3 Immediate Inhibitory Action of KP-496 on Conjunctival Vascular Permeability Response
  • KP-496 and its medium prepared according to the method shown in Example 2 were used as an eye drop test drug and an eye drop medium.
  • a pranlukast suspension prepared in the same manner as in Example 2 was used.
  • Table 2 3.5 vol% ethanol-containing physiological saline solution was similarly injected into the animals of the non-induced group.
  • the guinea pig was anesthetized with ether, lethal to death, and then the conjunctiva of both eyes was removed. After excision of the conjunctiva, 1 mL of the dye extract was added and sealed, and left to stand immersed for 5 days at room temperature in the dark. Thereafter, centrifugation (1500 rpm, 10 minutes, room temperature) was performed, the supernatant was collected, and the absorbance at a wavelength of 620 nm was measured. At the same time, the absorbance of the Evans blue standard solution was also measured, and a calibration curve was prepared to calculate the dye concentration ( ⁇ g / mL) and the total leakage dye amount ( ⁇ g / site) of each specimen.
  • the control group (group A), the test drug 1 group (group B), the control drug 1 group (group C) and the non-induced group (group D) were divided into 8 groups. went. 20 ⁇ L of the test drug or eye drop medium was dropped into both eyes of the guinea pig. After dropping, the posture during dropping was maintained for 60 seconds to prevent the test substance from flowing out. Immediately thereafter, pranlukast suspension or oral medium was administered orally.
  • FIG. 3 shows that, compared with the control group, the amount of total leaked pigment was significantly decreased in the test drug group, whereas no significant decrease was observed in the control group. Since the hyperpermeability reaction of the conjunctival blood vessel was induced 5 minutes after administration of the test substance, it was found that the test drug action was immediately and immediately exerted by transmucosal administration of the test drug.
  • KP-496 that permeated through the multi-layered squamous epithelium is thought to exert its action, but in the nasal mucosa of allergic rhinitis patients, a metaplasia phenomenon that changes from multi-columnar columnar epithelium to stratified squamous epithelium occurs and resembles the conjunctiva From the Mygin N, Sorensen H, Pedersen C.B: The nasal mucosa burning long-term treatment with the belomethasone dipropionate aol. The immediate effect of KP-496 on nasal mucosal blood vessels can be analogized.
  • transmucosal preparation for treating nasal congestion that is effective for immediate reduction / removal of nasal congestion. It can also be used in combination with other drugs for cold syndrome or rhinitis with nasal congestion.

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Abstract

L'invention porte sur une préparation thérapeutique transmucosale pour une obstruction nasale qui contient de l'acide 2-{N-[4-(4-chlorobenzènesulfonylamino)butyl]-N-{3-[(4-isopropyl-2-thiazolyl)méthoxy]benzyl}}sulfamoyl-benzoïque en tant que principe actif. Cette préparation a un effet de soulagement immédiat d'une obstruction nasale parmi les symptômes de la rhinite provoqués par un rhume, un pollinose, un rhume des foins, une rhinite allergique, etc.
PCT/JP2009/050421 2008-01-16 2009-01-15 Préparation thérapeutique transmucosale pour une obstruction nasale WO2009090976A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2008-006358 2008-01-16
JP2008006358A JP2011088825A (ja) 2008-01-16 2008-01-16 鼻閉症治療用経粘膜投与製剤

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WO2009090976A1 true WO2009090976A1 (fr) 2009-07-23

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Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04154766A (ja) * 1990-10-16 1992-05-27 Terumo Corp フェノキシ酢酸誘導体及びこれを含有する医薬製剤
JPH04154757A (ja) * 1990-10-16 1992-05-27 Terumo Corp フェノキシ酢酸誘導体及びこれを含有する医薬製剤
JPH05262736A (ja) * 1992-03-23 1993-10-12 Terumo Corp フェノキシ酢酸誘導体
JPH05279336A (ja) * 1992-03-23 1993-10-26 Terumo Corp フェノキシ酢酸誘導体
JPH0812569A (ja) * 1994-06-24 1996-01-16 Takeda Chem Ind Ltd 塩化カルニチン吸着固形物
JPH0912554A (ja) * 1995-06-30 1997-01-14 Terumo Corp フェノキシ酢酸誘導体及びこれを含有する医薬製剤
WO1997021691A1 (fr) * 1995-12-14 1997-06-19 Kaken Pharmaceutical Co., Ltd. Derives thiazole
WO1998008820A1 (fr) * 1996-08-26 1998-03-05 Yamanouchi Pharmaceutical Co., Ltd. Composes de benzenesulfone et sels de ces derniers
JPH10195038A (ja) * 1996-11-13 1998-07-28 Hokuriku Seiyaku Co Ltd ベンゼンスルホンアミド誘導体及びそれを含有する医薬
WO1998057935A1 (fr) * 1997-06-17 1998-12-23 Kaken Pharmaceutical Co., Ltd. Derives d'acide 2-sulfamoylbenzoique
WO2006009209A1 (fr) * 2004-07-22 2006-01-26 Kaken Pharmaceutical Co., Ltd. Agent préventif ou thérapeutique pour les maladies inflammatoires chroniques des poumons

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04154766A (ja) * 1990-10-16 1992-05-27 Terumo Corp フェノキシ酢酸誘導体及びこれを含有する医薬製剤
JPH04154757A (ja) * 1990-10-16 1992-05-27 Terumo Corp フェノキシ酢酸誘導体及びこれを含有する医薬製剤
JPH05262736A (ja) * 1992-03-23 1993-10-12 Terumo Corp フェノキシ酢酸誘導体
JPH05279336A (ja) * 1992-03-23 1993-10-26 Terumo Corp フェノキシ酢酸誘導体
JPH0812569A (ja) * 1994-06-24 1996-01-16 Takeda Chem Ind Ltd 塩化カルニチン吸着固形物
JPH0912554A (ja) * 1995-06-30 1997-01-14 Terumo Corp フェノキシ酢酸誘導体及びこれを含有する医薬製剤
WO1997021691A1 (fr) * 1995-12-14 1997-06-19 Kaken Pharmaceutical Co., Ltd. Derives thiazole
WO1998008820A1 (fr) * 1996-08-26 1998-03-05 Yamanouchi Pharmaceutical Co., Ltd. Composes de benzenesulfone et sels de ces derniers
JPH10195038A (ja) * 1996-11-13 1998-07-28 Hokuriku Seiyaku Co Ltd ベンゼンスルホンアミド誘導体及びそれを含有する医薬
WO1998057935A1 (fr) * 1997-06-17 1998-12-23 Kaken Pharmaceutical Co., Ltd. Derives d'acide 2-sulfamoylbenzoique
WO2006009209A1 (fr) * 2004-07-22 2006-01-26 Kaken Pharmaceutical Co., Ltd. Agent préventif ou thérapeutique pour les maladies inflammatoires chroniques des poumons

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MIZUTANI N. ET AL.: "Effects of KP-496, a novel dual antagonist of leukotriene D4 and thromboxane A2 receptors on nasal blockage in guinea pig models of allergic rhinitis", INFLAMMATION RESEARCH, vol. 57, no. 6, 2 July 2008 (2008-07-02), pages 247 - 251 *

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