TW201842934A - Antiallergic agent - Google Patents

Abstract

An object of the present invention is to provide a novel antiallergic agent. The present invention provides an antiallergic agent containing a quinolone antibacterial drug.

Description

 Antiallergic agent  

The present invention relates to an antiallergic agent which has a β-hexosaminidase free inhibitory activity and can alleviate allergy symptoms.

In recent years, people who have caused allergic symptoms such as pollen and food have become social problems, and anti-allergic agents and foods that alleviate the allergic symptoms of seizures are being developed.

In the treatment of allergy symptoms, it can be broadly classified into steroid therapy such as administration of steroid hormones and non-steroidal therapy such as antihistamine. Steroid therapy is very effective in alleviating allergy symptoms, but when it is administered for a long period of time, side effects such as osteoporosis, cataract, and thrombosis may occur.

In the mechanism of allergic symptoms, various chemical mediators such as histamine exist in particles present in cells such as basophilic cells and obese cells, and antigens are stimulated at specific sites on the surface of such cells. Degranulation is caused and the chemical medium is released outside the cell. It is known that due to the release of chemical mediators, allergic symptoms such as sneezing, runny nose, tearing, dermatitis, and asthma are caused.

The mechanism of allergic symptoms has been clarified, and in addition to reducing the amount of IgE, natural extracts and the like have also been explored to study non-steroidal therapies, which inhibit IgE and on the cell surface of obese cells and basophils. After the high-affinity IgE receptor (FcεRI) is expressed, degranulation of obese cells or basophilic balls occurs by antigen bridge.

For example, α- or γ-scorpionin (α- or γ-mangostin) of a peel extract of mangosteen (refer to Patent Document 1), and a strain of Oompora which is a kind of mildew can be produced. The sulochrin of the diphenyl ketone derivative (see Patent Document 2) and the forskolin of one of the dipterpene extracted from the Labiatae (refer to Patent Document 3) )Wait.

 [Previous Technical Literature]    [Patent Literature]  

[Patent Document 1] Japanese Patent Laid-Open Publication No. 2000-116356

[Patent Document 2] Japanese Patent Laid-Open No. Hei 8-92082

[Patent Document 3] Japanese Patent Laid-Open Publication No. 2003-252786

It is an object of the present invention to provide novel anti-allergic agents.

When the antibody IgE can inhibit degranulation of obese cells and basophilic balls after binding to FcεRI, it can directly cause alleviation of allergy symptoms. As an indicator of degranulation of a suppressor cell line, β-hexosaminidase (LB Schwartz, KF Austen, and SI Wasserman, Immunologic release of beta-hexosaminidase and beta-glucuronidase from purified rat serosal mast cells, J. Immunol., (1979) 123: p. 1445-1450), the present inventors, and the results of the inhibition of β-hexosaminidase release inhibition activity by using degranulation inhibition of basophilic spheroid cells as an index, and found that: Although it has not been used for the treatment of allergic diseases in the past, the quinolinone-based antibacterial agent having a degranulation promoting effect (Furuhata et al., Biol. Pharm. Bull. 21 (5) 461-464 (1998)) has an antiallergic effect. Function to complete the present invention.

That is, the present invention includes the following [1] to [4].

[1] An antiallergic agent containing a quinolinone antibacterial agent.

[2] The antiallergic agent according to [1], wherein the allergic disease is caused by spring catarrh, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, urticaria, and bronchial asthma. At least one selected from the group.

[3] The antiallergic agent according to [1] or [2], wherein the component of the quinolinone-based antibacterial agent is gatifloxacin, moxifloxacin, and tosufloxacin ( Tosufloxacin), sparfloxacin, sitafloxacin, fleroxacin, garenoxacin, levofloxacin, lomefloxacin hydrochloride, hydrochloric acid One or more selected from the group consisting of ciprofloxacin hydrochloride, enoxacin, ofloxacin, norfloxacin, and nadifloxacin.

[4] The antiallergic agent according to any one of [1] to [3], which is in the form of an internal preparation, an ointment, a cream, a liquid, a nasal spray, or an eye drop.

Furthermore, the present invention encompasses the following [5] to [8-4].

[5] A quinolinone-based antibacterial agent for use in the treatment of allergic diseases.

[6] A method for treating an allergic disease by administering a quinolinone-based antibacterial agent to a human-containing animal.

[7] The use of a quinolinone-based antibacterial agent for the treatment of allergic diseases.

[8] The use of a quinolinone-based antibacterial agent for the manufacture of a medicament for treating allergic diseases.

[5-2] The quinolinone-based antibacterial agent for use according to [5], wherein the allergic disease is caused by spring mucositis, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, urticaria And at least one selected from the group consisting of bronchial asthma.

[5-3] The quinolinone-based antibacterial agent to be used according to [5] or [5-2], wherein the component of the quinolinone-based antibacterial agent is gatifloxacin, moxifloxacin, and tofu Sand star, sparfloxacin, sitafloxacin, fleroxacin, galesacin, levofloxacin, lomefloxacin hydrochloride, ciprofloxacin hydrochloride, enoxacin, ofloxacin, norfloxacin And one or more selected from the group of nafloxacin.

[5-4] The quinolinone-based antibacterial agent to be used according to any one of [5], [5-2], or [5-3], wherein the quinolinone antibacterial agent is contained in the internal medicine. In a dose, ointment, cream, liquid, nose, or eye drop.

[6-2] The method for treating an allergic disease according to [6], wherein the allergic disease is caused by spring mucositis, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, urticaria, and bronchial asthma. At least one selected from the group.

[6-3] The method for treating an allergic disease according to [6] or [6-2], wherein the component of the quinolinone-based antibacterial agent is gatifloxacin, moxifloxacin, and tosufloxacin. , sparfloxacin, sitafloxacin, fleroxacin, galesacin, levofloxacin, lomefloxacin hydrochloride, ciprofloxacin hydrochloride, enoxacin, unfloxacin, norfloxacin and One or more selected from the group consisting of flatoxacin.

[6-4] The method for treating an allergic disease according to any one of [6], wherein the quinolinone-based antibacterial agent is an internal medicine or an ointment. In a lotion, cream, liquid, nose, or eye drop.

[7-2] The use of the quinolinone-based antibacterial agent according to [7], wherein the allergic disease is caused by spring mucositis, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, urticaria and At least one selected from the group consisting of bronchial asthma.

[7-3] The use of the quinolinone-based antibacterial agent according to [7] or [7-2], wherein the component of the quinolinone-based antibacterial agent is gatifloxacin, moxifloxacin, and toluene Sand star, sparfloxacin, sitafloxacin, fleroxacin, galesacin, levofloxacin, lomefloxacin hydrochloride, ciprofloxacin hydrochloride, enoxacin, eurfloxacin, norfloxacin And one or more selected from the group of nafloxacin.

[7-4] The use of the quinolinone-based antibacterial agent according to any one of [7], wherein the quinolinone-based antibacterial agent is an internal drug. , ointments, creams, liquids, nose drops, or eye drops.

[8-2] The use of the quinolinone antibacterial agent according to [8], wherein the allergic disease is caused by spring mucositis, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, urticaria and bronchus At least one selected from the group consisting of asthma.

[8-3] The use of the quinolinone-based antibacterial agent according to [8] or [8-2], wherein the component of the quinolinone-based antibacterial agent is gatifloxacin, moxifloxacin, and toxin Sand star, sparfloxacin, sitafloxacin, fleroxacin, galesacin, levofloxacin, lomefloxacin hydrochloride, ciprofloxacin hydrochloride, enoxacin, eurfloxacin, norfloxacin And one or more selected from the group of nafloxacin.

[8-4] The use of the quinolinone-based antibacterial agent according to any one of [8], [8-2], and [8-3], wherein the dosage form of the medicine for treating allergic diseases is oral administration Agent, ointment, cream, liquid, nasal spray, or eye drop.

The quinolinone-based antibacterial agent in the present invention is used as an antiallergic agent because it has a degranulation inhibitory action.

[Fig. 1] Fig. 1 is a graph showing the effect of suppressing the release of β-hexosaminidase from gatifloxacin.

[Fig. 2] Fig. 2 is a graph showing the release inhibitory effect of β-hexosaminidase of enfloxacin.

[Fig. 3] Fig. 3 is a graph showing the antiallergic effect of gatifloxacin in the experimental rat model of allergic conjunctivitis in the present invention.

[Fig. 4] Fig. 4 is a view showing the antiallergic effect of enfloxacin in the experimental rat model of allergic conjunctivitis of the present invention.

 [Formation of the Invention]  

The present invention includes an antiallergic agent containing a quinolinone-based antibacterial agent.

The quinolinone-based antibacterial agent of the present invention is one of a series of synthetic antibacterial agents, and is an agent which produces an antibacterial or bactericidal action by inhibiting DNA gyrase. The quinolinone-based antibacterial agent of the present invention contains a narrowly defined quinolinone-based antibacterial agent and a novel quinolinone-based antibacterial agent. Examples of the quinolinone-based antibacterial agent include gatifloxacin, moxifloxacin, tosufloxacin, sparfloxacin, sitafloxacin, fleroxacin, galaxacin, levofloxacin, and lomeisa hydrochloride. Star, ciprofloxacin hydrochloride, enoxacin, enfloxacin, norfloxacin, or nalfloxacin, or a salt thereof, especially gatifloxacin or ofloxacin, or Its salt is preferred. The salt is preferably a pharmaceutically acceptable salt or hydrate. For example, a salt of an alkali metal such as sodium, potassium or lithium, a salt of an alkaline earth metal such as calcium, magnesium or manganese, or an acid addition salt such as hydrochloric acid or sulfuric acid may be mentioned. The quinolinone-based antibacterial agent is not particularly limited, but the drug recognized in Japan is levofloxacin (trade name: Cravit), and ofloxacin (trade name: Tarivid) ), cinoxafloxacin (trade name: Gracevit), ciprofloxacin (trade name: Ciproxan), or gatifloxacin (trade name: Gatiflo) as a representative of the new quinolinone is particularly good.

The quinolinone-based antibacterial agent has a strong anti-granulation inhibitory effect and is useful as an anti-allergic agent. For allergic symptoms or allergic diseases to be the object of the present invention, spring mucositis, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, urticaria, bronchial asthma, sneezing, runny nose, tearing, Or itching and so on. Antiallergic agents can also be referred to as prophylactic or therapeutic agents for allergic diseases.

The content ratio of the quinolinone-based antibacterial agent may be, for example, 0.01 to 100% by mass, may be 0.1 to 10% by mass, or may be 0.1 to 5% by mass based on the antiallergic agent.

The present invention is a pharmaceutical product comprising the anti-allergic agent of the present invention. The content ratio of the antiallergic agent may be, for example, 0.01 to 100% by mass, may be 0.1 to 10% by mass, or may be 0.1 to 5% by mass based on the pharmaceutical.

The anti-allergic agent of the present invention may be a quinolinone-based antibacterial agent alone or in combination with other medicines (for example, ketotifen or a salt thereof), an optional carrier for a preparation, or a diluent to form an arbitrary dosage form. And as a medicine. The content of the above-mentioned ingredients in the pharmaceutical product is not particularly limited, but is preferably from 0.01 to 5% by mass, more preferably from 0.05 to 3% by mass, still more preferably from 0.1 to 2% by mass. The mass ratio of the quinolinone-based antibacterial agent to other medicines (quinolinone-based antibacterial agent: other medicines) may be about 1: (0.1 to 10) or about 1: (0.9 to 1.1). The antiallergic agent of the present invention may contain ketotifen or a salt thereof or other pharmaceutical ingredients, and may or may not be included.

Examples of the dosage form of the anti-allergic agent or the pharmaceutical of the present invention include an internal preparation, an ointment, a cream, a liquid, a nasal spray, or an eye drop.

The anti-allergic agent or the pharmaceutical product of the present invention can be directly mixed and dispersed by a quinolinone-based antibacterial agent, a carrier for a preparation, a diluent, or other medicines by a general method for producing a pharmaceutical product, and then processed into a desired one. The form is available. Specifically, for example, a known solvent, a solubilizing agent, an isotonic agent, a preservative, an antioxidant, an excipient, a binder, a lubricant, an emulsifier or a stabilizer, which are acceptable for a pharmaceutical product, may be added.

In the form of the anti-allergic agent or the pharmaceutical preparation of the present invention, when it is an internal preparation, for example, a tablet, a granule, a fine granule, a hard capsule, a soft capsule, a powder, a buccal tablet, In the case of an external preparation, for example, a skin external preparation such as an eye drop, an injection, an ointment or a cream, or a suppository can be mentioned.

In the dosage form of the anti-allergic agent or the pharmaceutical of the present invention, a carrier or a diluent which is acceptable for the pharmaceutical product may be separately added. In the internal preparation, for example, an excipient, a disintegrating agent, a disintegration adjuvant, a binder, a lubricant, a fluidizing agent, a buffering agent, a curing agent, a stabilizer, an antioxidant, a reducing agent, and a cooling agent may be added. A chemical, a sweetener, a flavoring agent, a flavoring agent, a coloring agent, a surfactant, a plasticizer, a solubilizing agent, a suspending agent, a dispersing agent, an emulsifier, a dissolution adjuvant, a glossing agent, or a coating agent. Further, as the external preparation, for example, a solvent, a dissolution adjuvant, an emulsifier, an isotonic agent, a buffer, a pH adjuster, or the like may be added. A stabilizer, a preservative, or an antioxidant may be added as needed.

In the present invention, among the aforementioned dosage forms, eye drops are particularly preferred. A carrier or a diluent which can be allowed to be added to the eyedrops can be added, and a buffering agent, an isotonic agent, a dissolution adjuvant, a preservative, a thickener, and a chelate can be added as long as the problem of the present invention can be solved. Various additives such as a mixture or a pH adjuster.

The pH of the eye drop of the present invention is not particularly limited as long as it is within the allowable range of ophthalmology, and the pH is preferably from 3 to 12, more preferably from 4 to 11, and even more preferably from 5 to 10. The best is 5 to 9, and the better is 6 to 8.

The osmotic pressure ratio of the eye drop agent of the present invention is preferably a pressure ratio of 0.5 to 5, more preferably a pressure ratio of 0.7 to 2, and still more preferably a pressure ratio of 0.9 to 1.5.

The pH adjuster is not particularly limited, and examples thereof include hydrochloric acid or sodium hydroxide, and the pH adjuster can be added in an appropriate amount within the above range.

The isotonic agent is not particularly limited, and examples thereof include glucose, D-sorbitol, sodium chloride, D-mannitol, and glycerin, and glycerin is preferred. The content of glycerin is determined by calculating the amount of the eye drops to be equal.

The solvent is not particularly limited, and examples thereof include purified water, ethanol, propylene glycol, polyethylene glycol, Macrogol, or edible oil (sesame oil, corn oil, olive oil, etc.). The dissolution adjuvant is not particularly limited, and examples thereof include propylene glycol, D-mannitol, benzyl benzoate, ethanol, triethanolamine, sodium carbonate, or sodium citrate.

The emulsifier is not particularly limited, and examples thereof include carboxymethylcellulose (carboxylose), hydroxypropylcellulose, propylene glycol, polyvinylpyrrolidone, methylcellulose, glyceryl monostearate, and polyvinyl alcohol. , lecithin (egg lecithin, soy lecithin), deoxycholic acid, polyoxyethylene castor seed oil, polyoxyethylene hardened castor seed oil, polyoxyethylene ethyl polyoxypropyl propyl Glycol, monooleic acid polyoxyethylene ethyl sorbitan ester (polysorbate 80), or monolauric acid polyoxyethylene ethyl sorbitan ester, etc., and lecithin is preferred, egg yolk lecithin Better. The content of the emulsifier may be from 0.1 to 3.0% by mass based on the total anti-allergic agent or pharmaceutical product.

The buffering agent is not particularly limited, and examples thereof include citrate (trisodium citrate dihydrate, sodium citrate, disodium citrate, etc.), and phosphate (sodium dihydrogen phosphate, sodium phosphate, disodium hydrogen phosphate). , potassium dihydrogen phosphate, potassium phosphate, dipotassium hydrogen phosphate, etc.), borate (sodium borate, potassium borate), acetate (sodium acetate trihydrate, sodium acetate, potassium acetate, etc.), or carbonate (sodium carbonate, Sodium bicarbonate, etc.). The content of the buffer may be 0.001 to 3.0% by mass based on the total anti-allergic agent or pharmaceutical product.

The stabilizer is not particularly limited, and examples thereof include EDTA, sodium oleate, casein, or casein sodium salt. EDTA includes EDTA-2Na, or EDTA-4Na, and the like. The content of EDTA may be 0.001 to 0.1% by mass based on the total anti-allergic agent or pharmaceutical product.

The preservative is not particularly limited, and examples thereof include a 4-grade ammonium salt (benzalkonium chloride, benzothonium chloride, etc.), p-hydroxybenzoic acid. An acid ester (ethyl p-hydroxybenzoate, methyl p-oxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate), chlorobutanol, benzyl alcohol, sodium dehydroacetate, or sorbic acid. The antioxidant is not particularly limited, and examples thereof include sodium sulfite and ascorbic acid. The content of the preservative may be 0.001 to 3.0% by mass based on the total amount of the antiallergic agent or the pharmaceutical.

The thickener is not particularly limited, and examples thereof include a carboxyvinyl polymer, sodium chondroitin sulfate, refined lanolin, sodium hyaluronate, hydroxyethyl cellulose, or hypromellose. The content of the thickener may be 0.001 to 3.0% by mass based on the total amount of the antiallergic agent or the pharmaceutical.

Examples of the antioxidant include polyphenol, ascorbic acid, tertiary butyl hydroquinone, butyl hydroxyanisole, butylhydroxytoluene, L-cysteine hydrochloride, sodium hydrogen sulfite, or α- Tocopherol, etc., or such derivatives. The antioxidant may be contained in an amount of 0.001 to 3.0% by mass based on the total anti-allergic agent or pharmaceutical product.

The anti-allergic agent or the pharmaceutical of the present invention may be administered to an animal other than a human or a human. Animals other than humans are not particularly limited, and examples thereof include cows, horses, pigs, sheep, goats, llamas, alpacas, camels, rabbits, lynx, foxes, chinchilla, and geese. Chicken, duck, dog, cat, or hamster.

The administration amount of the anti-allergic agent or the pharmaceutical of the present invention is appropriately selected depending on the dosage form, the administration route, the administration target, the age, the body weight, the administration interval, and the like. For oral administration, for example, an adult (60 kg) of the anti-allergic agent or pharmaceutical of the present invention may be administered in an amount of from about 0.0001 mg to about 100 g, from about 0.001 mg to about 50 g, and from about 0.01 mg to about 20 g per day. , about 0.1 mg to about 5 g, and the like. The administration interval of the anti-allergic agent or the pharmaceutical of the present invention is appropriately selected depending on the dosage form, the subject to be administered, and the like, and may be, for example, about 1 to 3 times per day, but about 1 to 3 times per 2 or 3 months. can. The number of administrations is appropriately selected depending on the dosage form, the target of administration, and the like. For example, it may be administered once, but it may be administered continuously at regular intervals.

[Examples]

Hereinafter, the present invention will be described in more detail by way of examples, but the invention is not limited thereto. Further, in the examples, the "%" of the concentration means "mass/capacity%" unless otherwise specified.

 [Example 1 Degranulation inhibition test]  

In this example, degranulation of cells was assessed by measuring the activity of β-hexosaminidase. Methods as below.

In the present specification, M means mol/L, and mM means mmol/L.

<Modulation of the substance to be tested>

Gatifloxacin (LKT Laboratories, Inc.) and ofloxacin (LKT Laboratories, Inc.) are HEPES Tyrode BSA Buffer (140 mM NaCl, 2.7 mM KCl, 1.8 mM CaCl ₂ ‧2H ₂ O, 12.1 mM NaHCO ₃ , 0.4 mM NaH ₂ PO ₄ ‧2H ₂ O, 0.5 mM MgCl ₂ ‧6H ₂ O, 5.7 mM glucose, 25 mM HEPES, 0.1% BSA) were dissolved and each became 0.05 w/v%, 0.3 w/ v% and 0.145w/v%, and then diluted to the desired concentration for use. Further, the positive control used Trullilast (Dawa Pharmaceutical Industry Co., Ltd.).

<Pharmaceutical and reagent preparation>

The minimal medium was Dulbecco's Modified Eagle's Medium (hereinafter DMEM, trade name: GIBCO, Thermo Fisher Scientific Co., Ltd.). A23187 (SIGMA-ALDRICH), which is a degranulation-inducing substance, was dissolved in dimethyl sulfoxide (DMSO, Wako Pure Chemical Industries, Ltd.), and a final concentration of 10 μM of A23187 solution was prepared with HEPES Tyrode BSA Buffer. The matrix solution was prepared by dissolving 4-nitrophenyl N-acetyl-β-D-glucosaminide (SIGMA-ALDRICH) in 0.4 M citrate buffer ( The pH 4.5) was 2 mM, and the reaction stop solution was a 0.2 M glycine buffer (pH 10.7).

<Test method>

The basophilic spheroid cell line (RBL-2H3 cells) was adjusted to 3×10 ⁵ cells/mL in DMEM containing 10 v/v% fetal fetal serum (FCS; Fetal calf serum), and seeded in 96-well microplates. 200 μL/well was incubated overnight at 37 ° C in a 5 v/v% CO ₂ incubator. On the next day, the medium was removed by suction, washed with DMEM, and then MEM 200 μL/well was added thereto, and cultured at 37 ° C in a 5 v/v% CO ₂ incubator for 3 to 4 hours. After the culture, the DMEM was removed by suction, and the A23187 solution was added at 100 μL/well. The test substance was added to the concentration of the first and second tables simultaneously with the addition of the A23187 solution, and the temperature was constant at 37 ° C, 5 v/v% CO _{2 .} Incubate for 30 minutes. After the incubation, the 96-well microplate was ice-cooled for 10 minutes to stop the reaction, and in the other 96-well microplate, the culture supernatant was collected at 40 μL × 2 in each well, and the residue was removed by suction. Next, 0.1w/v% Triton X-100 was added to the 96-well microplate, 100 μL/well, and after ultrasonic treatment for 1 minute, the culture supernatant was also similarly applied to each well of the corresponding 96-well microplate. The cell lysate was recovered by 40 μL × 2. The 96-well microplate of the recovered culture supernatant and cell lysate was preincubated at 37 ° C for 5 minutes, and a matrix solution of 100 μL/well was added thereto, and after mixing, the mixture was incubated at 37 ° C for 30 minutes. Then, 200 μL/well of the reaction stop solution was added and mixed, and the absorbance at 405 nm was measured with a microplate reader (Power Scan MX, DS Pharma BioMedical Co., Ltd.).

<calculation method>

The liberation rate (%) of β-hexosaminidase was calculated by the following formula.

[Number 1] β-hexosaminidase free rate (%) = 100 × [(S-Sc) / {(S-Sc) + (CL-CLc)}]

S: absorbance of the culture supernatant

Sc: absorbance of the culture supernatant when added in the order of the reaction stop solution → matrix solution

CL: absorbance of cell lysate

CLc: absorbance of cell lysate when added in the order of reaction stop solution → matrix solution

<Result>

The results are shown in Tables 1 and 2. Gatifloxacin and ofloxacin showed excellent inhibitory effects on the degranulation reaction (*: p < 0.05, corresponding buffer group 2 or 7, Dunnett multiple comparison assay).

 [Example 2 Allergic conjunctivitis inhibition test]  

In this example, an experimental rat model of allergic conjunctivitis was used to evaluate quinolinone-based antibacterials (gatifloxacin or ofloxacin) and antihistamines of ketotifen fumaric acid. The combined use of salt. Methods as below.

<sample modulation>

As the test solution, the following three groups were prepared.

1. Control group (physiological saline)

2. Separate group (Zaditen (registered trademark) eye drops 0.05w/v% (ketotifen 0.05w/v%), made by Alcon, Japan)

3. Combined with group (each quinolinone antibacterial medical eye drops (in gatifloxacin (0.3w / v%) or ofloxacin (0.3w / v%)) dissolved or suspended meperidin The ketone is made to be 0.05w/v%)

<Pharmaceutical and reagent preparation>

1w/v% egg albumin (Grade V, manufactured by Sigma Aldrich) / physiological salt solution (manufactured by Otsuka Pharmaceutical Co., Ltd.) and 1w/v% Evans Blue (manufactured by Wako Pure Chemical Industries, Ltd.) / physiological saline solution An equal amount of the mixture.

An acetone (manufactured by Wako Pure Chemical Industries, Ltd.) / 0.5 w/v% sodium sulfate (manufactured by Wako Pure Chemical Industries, Ltd.) aqueous solution (7:3) was used as the extract.

<Test method>

Rats (Wistar, male, 5 weeks old at the time of purchase, purchased from SLC, Japan) were inhaled and anesthetized with diethyl ether, and the previously prepared ovalbumin antiserum (antibody price 4) was placed in both eyes. Subconjunctival injection and passive sensitization (20 μL/eye, n=4 to 6/group). After 48 hours, 1 mL of the initiation solution was administered intravenously to induce an allergic reaction locally in the conjunctiva. The test solution was administered to the eye 15 minutes before the initiation of the allergy and before the initiation of the test (2 times). After the reaction was initiated for 30 minutes, the rats were euthanized, and the lower eyelid conjunctiva was taken out along the conjunctival dome, and the tissue weight was measured, and the extract was added for extraction overnight. The extract was separated by centrifugation overnight, and the absorbance at 620 nm of the supernatant was measured.

Due to an allergic reaction, Evans Blue leaks when the blood vessels are permeable, and the less the amount of the leaked pigment, that is, the more the vascular permeability is inhibited, the more anti-allergic effect can be judged. The amount of leaked pigment per unit tissue (μg/g) was determined from a standard curve prepared in advance as an index of the inhibitory effect.

<Result>

The results are shown in Tables 3 and 4. It was confirmed that the anti-allergic effect of gatifloxacin and ofloxacin showed an additive anti-allergic effect when combined with meperidone-fumarate (*: p<0.05, corresponding control group, no corresponding t-test) (Independent sample t-test)).

 [Industry use possibility]  

The present invention is useful in the field of medicine such as the treatment of allergies.

Claims (8)

 An anti-allergic agent containing a quinolinone-based antibacterial agent.    The anti-allergic agent according to claim 1, wherein the allergic disease is caused by spring catarrh, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, urticaria and bronchial asthma. At least one selected from the group.    The anti-allergic agent according to claim 1 or 2, wherein the quinolinone-based antibacterial agent is composed of gatifloxacin, moxifloxacin, and tosufloxacin. , sparfloxacin, sitafloxacin, fleroxacin, garenoxacin, levofloxacin, lomefloxacin hydrochloride, cyclopropane hydrochloride One or more selected from the group consisting of ciprofloxacin hydrochloride, enoxacin, ofloxacin, norfloxacin, and nadifloxacin.    The anti-allergic agent according to any one of claims 1 to 3, which is in the form of an internal preparation, an ointment, a cream, a liquid, a nasal spray, or an eye drop.    A quinolinone-based antibacterial agent is used for the manufacture of a medicament for treating allergic diseases.    The use of the quinolinone-based antibacterial agent according to claim 5, wherein the allergic disease is caused by spring mucositis, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, urticaria and bronchial asthma. At least one selected from the group.    The use of the quinolinone-based antibacterial agent as described in claim 5 or 6, wherein the quinolinone-based antibacterial agent is composed of gatifloxacin, moxifloxacin, and tosufloxacin. Sparfloxacin, statabofloxacin, fleroxacin, galesacin, levofloxacin, lomefloxacin hydrochloride, ciprofloxacin hydrochloride, enoxacin, eurfloxacin, norfloxacin, and fluoro One or more selected by Shaxing.    The use of the quinolinone-based antibacterial agent according to any one of the items 5 to 7, wherein the pharmaceutical preparation for the treatment of allergic diseases is an internal preparation, an ointment, a cream, or a liquid preparation. , nose drops, or eye drops.