KR20060120204A - Preventive and/or remedy for exudative otitis media - Google Patents

Abstract

A preventive and/or a remedy for exudative otitis media containing pranlukast hydrate as the active ingredient. The pranlukast hydrate contained in the above preventive and/or remedy for exudative otitis media has an effect of reducing middle ear exudate and, therefore, is useful as a drug for ameliorating various symptoms such as hearing disorder, ringing in the ear and ear obstruction.

Description

Prevention and / or treatment of exudative otitis media {PREVENTIVE AND / OR REMEDY FOR EXUDATIVE OTITIS MEDIA}

The present invention relates to a prophylactic and / or therapeutic agent for exudative otitis media containing franlukast hydrate as an active ingredient.

The number of patients with otitis media (medical care) is 30.5 million (Ministry of Health, Labor and Welfare: 2001), and about 40-50% of them are exudative otitis media.

Exudative otitis media is a type of otitis media in children and the elderly, and when the ear canal functioning to connect the middle ear and the nose worsens, the pressure regulation inside and outside the eardrum becomes poor, and the middle ear becomes negative pressure, so fluid leaks from the mucous membrane. Trouble me Therefore, symptoms such as hearing loss and ear obstruction are shown. If acute upper respiratory tract, chronic sinusitis, allergic rhinitis and adenoid hypertrophy are present in the patient's background, inflammation of the nose or throat always affects the middle ear through the ear canal, and thus is easily naturalized and refractory. When exudative otitis media is refractory, early treatment is important because aftereffects such as hearing loss remain and necessity of surgery occurs. In children, it is difficult to frequently perform surgical procedures such as tympanic dissection and tympanic tube indwelling, and a drug for minimizing surgical treatment is required.

In general, the therapeutic drug for exudative otitis media mainly includes expectorant drugs (e.g. carbocysteine) or macrolide antibiotics (e.g. ethyl succinate erythromycin, kurarithromycin, etc.), but sufficient effect Since no was obtained, the development of a highly effective oral agent was urgently desired.

Meanwhile, 4-oxo-8- [4- (4-phenylbutoxy) benzoylamino] -2- (tetrazol-5-yl) -4H-1-benzopyran 1/2 hydrate (general name: franlukast Hydrate; trade name Onon) is used as a therapeutic agent for bronchial asthma or allergic rhinitis, and is a drug having sufficient safety. In addition, although the franlukast hydrate has been reported (refer nonpatent literature 1) which shows the efficacy in the model of the condition of a rat exudative otitis media, the literature does not describe the efficacy in humans at all.

Non-Patent Document 1: Auris Nasus Larynx, (Netherlands), 2002, p. 127-132

Disclosure of the Invention

Problems to be Solved by the Invention

An object of the present invention is to provide an agent for preventing and / or treating otitis media or otitis media which is excellent in efficacy and can be orally administered to human patients. ·

Means to solve the problem

In view of the above problems, the inventors of the present invention have conducted extensive studies, and as a result, the franlukast hydrate surprisingly reduces middle ear storage and improves hearing, ear obstruction, and the like. Clinically discovered for the first time useful as a prophylactic and / or therapeutic agent, the present invention has been completed.

That is, the present invention

(1) a prophylactic and / or therapeutic agent for otitis media or otitis media, characterized by containing franlukast hydrate,

(2) the prophylactic and / or therapeutic agent according to the preceding item (1), wherein the otitis media is an exudative otitis media;

(3) the prophylactic and / or therapeutic agent according to the preceding item (1), which improves one or more symptoms selected from deafness, tinnitus and ear obstruction.

(4) the prophylactic and / or therapeutic agent according to item (1), which is a reducing agent for exudate,

(5) a prophylactic and / or therapeutic agent for deafness, tinnitus or ear obstruction, characterized by containing franlukast hydrate,

(6) the prophylactic and / or therapeutic agent according to the preceding item (1) or (5), wherein the dose per day of the franlukast hydrate is 50 to 450 mg,

(7) the prophylactic and / or therapeutic agent according to the preceding item (6), wherein the daily dose of franlukast hydrate is 112.5 mg, 225 mg or 450 mg,

(8) the prophylactic and / or therapeutic agent according to the preceding item (7), wherein the dosage per day of the franlukast hydrate is 450 mg, and 225 mg is administered twice a day;

(9) The dosage per day of a patient of franlukast hydrate is 450 mg, and the capsule containing 112.5 mg of franlukast hydrate is administered 2 capsules per time, l twice a day, as described in the preceding paragraph (8). Prophylactic and / or therapeutic agents,

(10) The prophylactic and / or therapeutic agent according to the preceding item (1) or (5), wherein the daily dose of franlukast hydrate is 2 to 10 mg per 1 kg of body weight of the patient,

(11) The prophylactic and / or therapeutic agent according to the preceding item (10), wherein the daily dose of franlukast hydrate is 7 mg per 1 kg of body weight of the patient,

(12) the prophylactic and / or therapeutic agent according to the preceding item (6), wherein the daily dose of the franlukast hydrate is 50 mg, 70 mg, 100 mg, 140 mg, 200 mg, or 280 mg;

(13) a combination of franlukast hydrate, one or two or more selected from expectorant, antibiotic, antihistamine, antiallergic, steroid, nonsteroidal anti-inflammatory drug, anti-inflammatory enzyme, and herbal medicine Medicine,

(14) A method for preventing and / or treating exudative otitis media in a mammal, wherein the franlukast hydrate is administered to the mammal at 2 to 10 mg / kg per day,

(15) A prophylactic and / or therapeutic agent for deafness, tinnitus or ear obstruction in a mammal, characterized by administering 2 to 10 mg / kg of franlukast hydrate to a mammal per day,

(16) 1 per day of franlukast hydrate selected from expectorants, antibiotics, antihistamines, antiallergic drugs, steroid drugs, nonsteroidal anti-inflammatory drugs, anti-inflammatory enzymes, and herbal medicines A method for preventing and / or treating exudative otitis media in a mammal, comprising administering a species or two or more species to a mammal,

(17) 1 per day of franlukast hydrate, selected from expectorant, antibiotic, antihistamine, antiallergic, steroid, nonsteroidal anti-inflammatory drug, anti-inflammatory enzyme, and herbal medicine A method for preventing and / or treating hearing loss, tinnitus, or ear obstruction in a mammal, comprising administering a species or two or more species to the mammal, and

(18) the use of franlukast hydrates for the manufacture of agents for the prevention and / or treatment of hearing loss, tinnitus or ear obstruction;

It is about.

Effects of the Invention

According to the present invention, an effective otitis media or otitis media, in particular an exudative otitis media, is provided to prevent and / or treat various symptoms of otitis media or otitis media, in particular otitis media. In addition, the present invention can improve the hearing loss, tinnitus, and ear obstruction associated with exudative otitis media.

To practice the invention  Best form for

Franlukast hydrate used in the present invention is formula (A)

4-oxo-8- [4- (4-phenylbutoxy) benzoylamino] -2- (tetrazol-5-yl) -4H-1-benzopyran 1/2 hydrate represented by

[Method for Preparing Compound of the Invention]

The production of francaste hydrate can be carried out according to the method described in, for example, Japanese Patent Laid-Open No. 61-050977. ·

[toxicity]

The toxicity of franlukast hydrate is very low and it has been confirmed that it is safe enough for use as a medicine. For example, as acute toxicity of franlukast hydrate, the minimum lethal dose was 2000 mg / kg or more when administered orally or subcutaneously to rats or rats (all males).

[Application to Drugs]

Franlukast hydrate is useful as a medicament for the prevention and / or treatment of otitis media or otitis media, especially exudative otitis media. Franlukast hydrate is also useful as a medicament for the prevention and / or treatment of hearing loss, tinnitus and ear obstruction because it improves various symptoms such as hearing loss or tinnitus associated with exudative otitis media.

 Medicines containing franlukast hydrate as an active ingredient can be used systemically or locally.

 Although the dosage of franlukast hydrate depends on age, weight, a symptom, a therapeutic effect, an administration method, or a treatment time, what is necessary is just to administer individually, so that the desired effect of this invention may be acquired. For example, the dosage per day of human patient is preferably about 25 mg to about 2500 mg, more preferably about 112.5 mg to about 450 mg, more preferably 225 mg to 450 mg.

In addition, the dosage per day in the case of administering franlukast hydrate to a child is preferably about 2 to l0 mg, more preferably about 5 mg to about 8 mg, and more preferably per kg of pediatric patient. Is about 7 mg. In the case of administration to pediatric patients weighing more than l2 kg and less than 18 kg, the daily dose is preferably about 50 to 100 mg per day, more preferably about 50 mg or about 100 mg per day of lancastast hydrate. to be. As for the daily dose when administering to the pediatric patient whose body weight is 18 kg or more and less than 25 kg, about 70-140 mg per day of franlukast hydrate is preferable, More preferably, it is about 70 mg or about 140 mg. In the case of administration to a pediatric patient weighing 25 kg or more and less than 35 kg, the daily dose is preferably about 100 mg to about 200 mg per day, more preferably about 100 mg or about 200 mg of franlukast hydrate. . As for the daily dose when administering to the pediatric patient whose body weight is 35 kg or more and less than 45 kg, about 140-280 mg of franlucast hydrate is preferable per day, More preferably, it is about 140 mg or about 280 mg.

As the administration method, either oral administration or parenteral administration is preferably used, but oral administration is more preferable. In addition, the administration is, for example, in the case of oral administration, the dosage is once to several times a day, preferably once to about four times a day, more preferably once to about two times a day. It is desirable to divide.

Of course, as mentioned above, since a dose, an administration method, or the frequency of administration vary with various conditions, the dosage per patient per day may be less than the said range, and may exceed a range.

When franlukast hydrate is prepared as the medicament, it can be made into a formulation known per se. The preparation may be an oral solid preparation or an oral solution for oral administration, or an injection, external preparation, suppository or inhalant for parenteral administration.

As an oral solid preparation for oral administration, a tablet, a pill, a capsule, a powder, a granule, etc. are mentioned.

In such an oral solid agent, the franlukast hydrate is mixed as it is or with an additive or granulated (for example, stirring granulation method, fluidized bed granulation method, dry granulation method, electric stirring fluidized bed granulation method, etc.), and a conventional method. (For example, capsule filling in the case of capsules, tableting in the case of tablets, etc.). The said additive may mix | blend suitably 1 type, or 2 or more types. As the additive, for example, excipients (for example, lactose, mannitol, glucose, microcrystalline cellulose, corn starch, etc.), binders (for example, hydroxypropyl cellulose, polyvinylpyrrolidone, magnesium metasilicate, etc.) , Dispersants (e.g., corn starch, etc.), disintegrants (e.g., calcium cellulose glycolate, etc.), glidants (e.g., magnesium stearate, etc.), stabilizers, dissolution aids (e.g., glutamic acid) , Aspartic acid, etc.), water-soluble polymers [for example, celluloses (for example, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, etc.), synthetic polymers (for example, polyethylene glycol, polyvinylpi Or a sweetener (for example, white sugar, powdered sugar, sucrose, fructose, glucose, lactose, reduced maltose syrup, powdered reduced maltose syrup, glucose fructose liquid) Sugar, fructose glucose liquid sugar, honey, sorbitol, maltitol, mannitol, xylitol, erythritol, aspartame, saccharin, sodium saccharin, and the like). In addition, granules or tablets may be coated with a coating agent (for example, white sugar, gelatin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose phthalate, etc.), etc. as needed, and the said coating may be two or more layers. In the case of preparation as a capsule, the above excipient is appropriately selected, and the capsule is filled with a coating agent appropriately mixed with, or granulated with, or granulated with franlukast hydrate, or filled with a suitable capsule base (gelatin, etc.). Glycerin or sorbitol or the like may be added to the capsule base to increase plasticity. If necessary, coloring agents or preservatives [sulfur dioxide, parabens (methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate)] and the like can be added to these capsule bases. Capsules include hard capsules or soft capsules.

In addition, it is preferable that one or several tablets or capsules are administered once, preferably 1 to about 2 tablets per time. For this reason, it is preferable that tablets or capsules are manufactured so that about 50-250 mg, preferably about 100-120 mg, especially about 112.5 mg of francaste hydrate is contained per tablet or capsule.

Examples of the oral solution for oral administration include water, suspensions, emulsions, syrups, dissolution-type preparations (for example, dry syrups), elixirs, and the like. In such an oral solution, the franlukast hydrate is dissolved, suspended or emulsified in a diluent (for example, purified water, ethanol or a mixture thereof, etc.) generally used as an internal solution. In addition, this liquid may contain a humectant, a suspending agent, an emulsifier, a sweetener, a flavoring agent, a fragrance, a preservative or a buffer. In addition, the dry syrup can be produced by, for example, mixing lanucast hydrate with white sugar, powdered sugar, sucrose, fructose, glucose or lactose. The dry syrup may be granulated according to a conventional method.

Formulations for parenteral administration include external preparations or injections. Examples of the formulation of the external preparation include an ointment, a gel, a cream, a poultice, a patch, a linen, a spray, an inhalant, or a spray.

Ointments are prepared by known methods. Ointments are prepared, for example, by blending or melting franlukast hydrate in a base. The ointment is selected from those known or commonly used. As the ointment base, for example, higher fatty acids or higher fatty acid esters (adipic acid, myristic acid, palmitic acid, stearic acid, oleic acid, adipic acid ester, myristic acid ester, palmitic acid ester, stearic acid ester) , Oleic acid esters, etc.), lead (such as beeswax, spermaceti, ceresin, etc.), surfactants (polyoxyethylene alkyl ether phosphate esters, etc.), higher alcohols (cetanol, stearyl alcohol, setstearyl alcohol, etc.), silicone oil (dimethyl Polysiloxanes), hydrocarbons (hydrophilic petrolatum, white petrolatum, purified lanolin, liquid paraffin, etc.), glycols (ethylene glycol, diethylene glycol, propylene glycol, polyethylene glycol, macrogol, etc.), vegetable oils (castor oil, olive oil, sesame oil) , Terpene oil, etc.), animal oil (mink oil, egg yolk oil, squalane, squalene, etc.), water, absorption accelerators or anti-inflammatory agents, and the like, 1 type or in mixture of 2 or more types is used. In addition, the ointment may contain a moisturizer, a preservative, a stabilizer, an antioxidant or a flavoring agent.

Gels are prepared by known methods. Gels are prepared, for example, by melting franlukast hydrate in a gel base. The gel base can be selected from those known or commonly used. As the gel base, for example, lower alcohols (ethanol, isopropyl alcohol, etc.), gelling agents (carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, etc.), neutralizing agents (triethanolamine, diisopropa) Nolamine etc.), surfactant (polyethyleneglycol monostearate etc.), gum, water, an absorption promoter, or an anti-inflammatory agent, etc. are mentioned, It is used 1 type or in mixture of 2 or more types. In addition, the gel agent may contain a preservative, an antioxidant, or a flavoring agent. ·

Creams are prepared by known methods. Creams are prepared, for example, by melting or emulsifying franlukast hydrate in a base. The cream base is selected from those known or commonly used. As the cream base, for example, higher fatty acid esters, lower alcohols, hydrocarbons, polyhydric alcohols (propylene glycol, 1,3-butylene glycol, etc.), higher alcohols (2-hexyldecanol, cetanol, etc.), emulsifiers (Polyoxyethylene alkyl ethers, fatty acid esters, etc.), water, an absorption accelerator, or an anti-inflammatory agent, etc. are mentioned, 1 type, or 2 or more types selected from these are mixed and used. In addition, the cream may contain a preservative, an antioxidant or a flavoring agent.

Poultice agents are prepared by known methods. A poultice agent is prepared by melting, for example, franlukast hydrate in a base, and applying it as a softener on the support. The coating base is selected from those known or commonly used. Examples of the base material include thickeners (polyacrylic acid, polyvinylpyrrolidone, gum arabic, starch, gelatin, methylcellulose, etc.), wetting agents (urea, glycerin, propylene glycol, etc.), fillers (kaolin, zinc oxide, talc). , Calcium, magnesium, and the like), water, a dissolution aid, a tackifier or an anti-inflammatory agent, and the like, and one or two or more selected from these may be used. In addition, the poultice agent may contain a preservative, an antioxidant, or a flavoring agent.

The patch is produced by a known method. The patch is prepared by, for example, melting the lanukast hydrate in a base for patching and applying it to the support substrate. The base for patch is selected from those known or commonly used. As a base for patching, a polymer base, fats and oils, a higher fatty acid, a tackifier, or an anti-inflammatory agent is mentioned, for example, 1 type or 2 or more types selected from these are mixed and used.

The lining agent is produced by a known method. For example, the lining agent is dissolved, suspended, or dissolved in francacast hydrate in one or two or more selected from water, alcohols (ethanol, polyethylene glycol, etc.), higher fatty acids, glycerin, soaps, emulsifiers, suspending agents, and the like. It is prepared by emulsification. In addition, the lining agent may contain a preservative, an antioxidant, or a flavoring agent.

Examples of injections for parenteral administration include solid injections used by dissolving or suspending them in a solution, suspension, emulsion, or solvent when taken. Injectables are used by dissolving, suspending or emulsifying franlukast hydrate in a solvent. Examples of the solvent include distilled water for injection, saline solution, vegetable oil, propylene glycol, polyethylene glycol, alcohols such as ethanol, and the like. These solvents are used 1 type or in combination of 2 or more types. In addition, the injection may contain a stabilizer, a dissolution aid (glutamic acid, aspartic acid, polysorbate 80 (registered trademark), etc.), a suspending agent, an emulsifying agent, a painless agent, a buffer, a preservative, and the like. They are preferably sterilized in the final process or prepared by aseptic operation. In addition, a sterile solid agent, for example, a freeze-dried product, may be prepared and dissolved in sterile or sterile distilled water or other solvent before use.

Other formulations for parenteral administration include, for example, sprays, inhalants or sprays. These preparations may contain, in addition to the diluents generally used, stabilizers such as sodium bisulfite and buffers which impart isotonicity, for example, isotonic agents such as sodium chloride, sodium citrate or citric acid. Methods of making sprays are described in detail, for example, in US Pat. Nos. 2,868,691 and 3,095,355.

Examples of inhalants include aerosols, powders for inhalation or liquids for inhalation. The inhalant may be in the form of dissolving or suspending in water or other suitable medium for use. These inhalants are prepared according to known methods.

Inhalants, for example, in the case of inhaled liquids, preservatives (benzalkonium chloride, parabens, etc.), colorants, buffering agents (sodium phosphate, sodium acetate, etc.), isotonic agents (sodium chloride, concentrated glycerin, etc.), thickeners (carboxy) Vinyl polymers) or absorption accelerators and the like as appropriate.

Powders for inhalation require lubricants (stearic acid and salts thereof), binders (starch, dextrin, etc.), excipients (lactose, cellulose, etc.), colorants, preservatives (benzalkonium chloride, parabens, etc.) or absorption accelerators. It selects suitably according to the manufacture.

When administering a liquid for inhalation, a nebulizer (atomizer, a nebulizer) is normally used, and when administering a powder for inhalation, a powder inhalation injector is usually used.

Other compositions for parenteral administration include franlukast hydrates, suppositories for rectal administration prescribed by conventional methods, pessaries for intravaginal administration, and the like.

In addition, the prophylactic and / or therapeutic agent for otitis media or otitis media, especially exudative otitis media, or the prophylactic and / or therapeutic agent for hearing loss, tinnitus, and ear obstruction (hereinafter, abbreviated as the prophylactic or therapeutic agent of the present invention) is another. It can also be used as a combination with a drug. When used in combination with other drugs, other drugs may be used to: 1) supplement and / or enhance the therapeutic effect of franlukast hydrates, 2) improve the dynamics and absorption of franlukast hydrates, reduce dosages, and / or 3) fran It is preferably used to alleviate the side effects of lucast hydrate.

The combination of the prophylactic or therapeutic agent of this invention, and another drug may be a form of the compounding agent which mix | blended both components in one formulation, and the form used as each formulation may be sufficient as it. The administration method in the case of using each of these preparations may be administered simultaneously, or may be administered with a time difference in the administration time of both preparations. In addition, administration by time difference may administer a franlukast hydrate first, may administer another medicament later, may administer another medicament first, and may administer a franlukast hydrate later, and each administration method is the same. It may be different. ·

The other drug may be a low molecular compound, or may be a polymer protein, polypeptide, polynucleotide (DNA, RNA, gene), antisense, decoy or antibody, vaccine or the like. The dosage of another drug can be suitably selected based on the dose used clinically. In addition, the compounding ratio of franlukast hydrate and other drugs can be appropriately selected depending on the age and weight of the subject to be administered, the method of administration, the time of administration, the target disease, the symptom or the kind of other drugs, and the like. For example, 0.01-100 weight part of other drugs may be used with respect to 1 weight part of franlukast hydrates. You may administer another drug combining the 1 type (s) or 2 or more types in combination at an appropriate ratio from the same group and the hetero group shown below.

Examples of other drugs include expectorants, antibiotics, antihistamines, antiallergic drugs, steroid drugs, nonsteroidal anti-inflammatory drugs, anti-inflammatory enzymes, and herbal medicines.

As the expectorant, for example, carbocysteine, ammonia fennel tablet, sodium hydrogencarbonate, bromine hexane hydrochloride, ammonium hydrochloride, sustained release ammonium hydrochloride, methylcysteine hydrochloride, acetylcysteine, L-ethylcysteine hydrochloride Etc. can be mentioned.

As an antibiotic, for example, penicillin antibiotics (for example, amoxicillin, etc.), cefem antibiotics (for example, Sephaclo, etc.) or microlide antibiotics (for example, ethyl succinate erythromycin, etc.) Etc. can be mentioned.

As antihistamine drugs, for example, cyproheptazine hydrochloride, d-maleic penfenarimin, mequitazine, azelastine, oxatomide, terfenadine, emedin fumarate, efinastin hydrochloride, astemizol, evastin , Cetirizine hydrochloride, bepotastine, fexofenadine, loratadine, desloratadine, olopatadine hydrochloride, TAK-427, ZCR-2060, NIP-530, mometazone fluorate, mizolastine, BP-294 , And last, oranoffin, or acrivastin.

Examples of anti-allergic agents include fumaric acid ketotifen and the like.

As a steroid drug, propionate clobetasol, diflorazone acetate, fluorinide, furan carboxylic acid metazone, dipropionate beta metazone, butyric acid beta metazone, valeric acid beta metazone, difluprenate, for example , Valeric acid Flucortolon, Amcinoid, Halcinoid, Dexamethasone, Propionate dexamethasone, Valeric acid dexamethasone, Dexamethasone acetate, Hydrocortisone acetate, Butyric acid hydrocortisone, Butyric acid hydrocortisone , Depropionate propionate, prednisolone valeric acid, prednisolone, fluorinolone acetonide, beclomethasone propionate, triamcinolone acetonide, pivalate flumezone, propionate alclomethazone, butyric acid clobetazone, prednisolone, Hydroxycortide, cortizone acetate, hydrocortisone, phosphate hydrocortisone nat Succinic acid hydrocortisone sodium, fluorocortizone acetate, prednisolone acetate, prednisolone succinate, prednisolone butyl acetate, sodium prednisolone phosphate, halopredone acetate, methyl prednisolone, methyl acetate Nizolone, Methylprednisolone sodium succinate, triamcinolone, triamcinolone acetate, dexamethasone phosphate, dexamethasone phosphate, paramethazone acetate, beta metazone, fluticasone propionate, budesonide, flunisolide, ST-126P , Ciclesonide, dexamethasonepalomithionate, mometazonefuran carbonnet, prasteronesulfonate, deplazacoat, methylprednisolone streptanate or methylprednisolone sodium succinate, etc. may be mentioned. .

As nonsteroidal anti-inflammatory drugs, for example, lion pyrine, sodium salicylate, aspirin, aspirin-dialuminate formulation, diflunisal, indomethacin, sprophene, upenamat, dimethylisopropylazulene, bupexamac, Pelbinac, Diclofenac Sodium, Tolmetin Sodium, Clinolyl, Penbufen, Navmethone, Proglumetacin, Indomethacin Farnesyl, Acemetasin, Pro maleemate maleic acid, Mofenzolac, Etodolac , Yvprofen, Yvprofenpiconol, naproxen, flurbiprofen, flurbiprofen accetyl, ketoprofen, phenopropene calcium, thiapropene oxaprozin, pranoprofen, roxof Lofen sodium, alminopropene, zaltoprofen, mefenamic acid, aluminum mefenamic acid, tolpenoic acid, flocfenin, ketophenylbutazone, oxyphenbutazone, pyricampam, tenoxycampa, ampicoxycampa, epi Resol, Tiaramid Hydrochloride, Tino Hydrochloride Dean, emol may be mentioned pajon, alcohol porphyrin, MIG renin, solbon, acetaminophen, phenacetin, such as the mesylate Totti dimethoxy triazine, Symmetry de formulation.

As an anti-inflammatory enzyme, a lysozyme chloride, a bromeline, a pronase, a cerapeptase, a streptokinase, a streptodonase compound, etc. are mentioned, for example.

Examples of the herbal medicines include Sojahotang, Hyangso Mountain, Younggyesulgamtang, Hwangrogunjungtang, Socheongryongtang, Maenggamtang, Wolbigaiseultang, Army Jar Tang, Maheung Bujasesintang, Jaryeongtang, and the like.

In addition, other medicaments include those not only discovered so far but also discovered in the future based on the above mechanisms.

Hereinafter, although an Example (clinical pharmacological test) and a manufacture example demonstrate this invention in detail, an Example is for understanding this invention well, and this invention is not limited to these.

For 21 cases of exudative otitis media in children, Franlukast hydrate (trade name: Onon dry syrup) was 7.0 mg / kg / day (70 mg / kg / day as dry syrup) for 4 weeks or more (up to 14 weeks). Administration was confirmed for effectiveness. Effectiveness (medical efficacy) evaluation was comprehensively judged by referring to eardrum findings and subjective symptoms (such as hearing loss, tinnitus, ear obstruction, etc.) mainly on the hearing test and the timpanogram. As a result, efficacy was observed in 13 cases (61.9%) among 21 cases of exudative otitis media in children. The effectiveness of Franlukast hydrate against exudative otitis media in children is based on the efficacy of existing drugs (combination of anti-inflammatory enzymes and antihistamines, anti-allergic drugs, herbal medicines, antibiotics, etc.) (E. clinic., 85, 5, 713-720 ( As compared to 1992). Franlukast hydrate has also been shown to be effective in patients who are not effective in the antibiotic succinic acid erythromycin (trade name: erythrosine dry syrup) or those who have been long-term natural.

From the above results, it has been clarified that the administration of franlukast hydrate improves hearing, tympanic findings, and the like, and therefore, franlukast hydrate is effective as a therapeutic drug for otitis media.

[Example]

Formulation Example l Preparation of Capsule

Franlukast hydrate (40 kg), lactose (19 kg), and an additive (suitable quantity) were spray-dried and granulated according to the conventional method, and granules containing 625 mg of franlukast hydrate were obtained in 1 g of granulated material. The obtained granulated product was filled in No. 3 capsules according to a conventional method such that the content of franlukast hydrate was 112.5 mg in one capsule, thereby obtaining a capsule containing franlukast hydrate.

Formulation Example 2 Preparation of Dry Syrup

Granule hydrate (10 kg), white sugar (80 kg), and an additive (suitable amount) were prepared according to a conventional method, and a dry syrup containing 100 mg of franlukast hydrate was obtained in 1 g of granules.

Franlukast hydrate is very useful as a prophylactic and / or therapeutic agent for exudative otitis media.

Claims (18)

A prophylactic and / or therapeutic agent for otitis media or otitis media, characterized by containing franlukast hydrate. The method of claim 1, An otitis media is an exudative otitis media. The method of claim 1, Prophylactic and / or therapeutic agents that ameliorate one or more symptoms selected from hearing loss, tinnitus, and ear obstruction. The method of claim 1, Prophylactic and / or therapeutic agent which is a reducing agent of exudate. An agent for the prevention and / or treatment of hearing loss, tinnitus, or ear obstruction, which contains franlukast hydrate. The method according to claim 1 or 5, A prophylactic and / or therapeutic agent, characterized in that the dose per day of franlukast hydrate is 50 to 450 mg. The method of claim 6, A prophylactic and / or therapeutic agent, characterized in that the daily dose of franlukast hydrate is 112.5 mg, 225 mg or 450 mg. The method of claim 7, wherein A prophylactic and / or therapeutic agent, characterized in that 450 mg of the daily dose of franlukast hydrate is administered, and 225 mg is administered twice daily. The method of claim 7, wherein A prophylactic and / or therapeutic agent characterized by administering a capsule containing 450 mg of frangicast hydrate per day, and twice a day, two capsules per day, containing 112.5 mg of franlukast hydrate. The method according to claim 1 or 5, A prophylactic and / or therapeutic agent, characterized in that the dosage per day of the patient's body weight is 2 to 10 mg of franlukast hydrate. The method of claim 10, A prophylactic and / or therapeutic agent, characterized in that the daily dose of franlukast hydrate is 7 mg per kilogram of body weight of the patient. The method of claim 5, A prophylactic and / or therapeutic agent, characterized in that the daily dose of franlukast hydrate is 50 mg, 70 mg, 100 mg, 140 mg, 200 mg, or 280 mg. A medicament comprising a combination of franlukast hydrates, expectorants, antibiotics, antihistamines, antiallergic drugs, steroid drugs, nonsteroidal anti-inflammatory drugs, anti-inflammatory enzymes, and one or more selected from herbal medicines . A method for preventing and / or treating exudative otitis media in a mammal, wherein the lanukast hydrate is administered to the mammal at 2 to 10 mg / kg per day. An agent for preventing and / or treating hearing loss, tinnitus, or ear obstruction in a mammal, wherein the lanukast hydrate is administered to the mammal at 2 to 10 mg / kg per day. 1 to 2 kinds of franlukast hydrate per day selected from 2-l0mg / kg, expectorant, antibiotic, antihistamine, antiallergic, steroid, nonsteroidal anti-inflammatory, anti-inflammatory enzyme, and herbal medicine The above method is administered to a mammal, The method for preventing and / or treating otitis media in a mammal. 1 to 2 selected from frangicast hydrate per day, 2-10 mg / kg, expectorant, antibiotic, antihistamine, antiallergic, steroid, nonsteroidal anti-inflammatory, anti-inflammatory enzyme, and herbal medicine A method for preventing and / or treating hearing loss, tinnitus, or ear obstruction in a mammal, characterized by administering more than one species to the mammal. Use of franlukast hydrate to prepare a prophylactic and / or therapeutic agent for hearing loss, tinnitus or ear obstruction.