JP6868972B2 - Anti-allergic composition - Google Patents

Description

The present invention relates to an antiallergic composition comprising fexofenadine hydrochloride, olopatadine hydrochloride, and one selected from the group consisting of loratadine, and glycyrrhizic acid and / or a salt thereof.

Fexofenadine Hydrochloride, Chemical Name 2- (4- {(1RS) -1-Hydroxy-4- [4- (hydroxydiphenylmethyl) piperidin-1-yl] butyl} phenyl) -2-methylpropanoic acid histamine In addition to receptor antagonism, it has various chemical mediator release inhibitory effects, inflammatory cytokine release inhibitory activity, and eosinophil migration inhibitory activity. Due to these effects, preparations containing fexophenazine hydrochloride include allergic rhinitis, urticaria, and pruritus associated with skin diseases such as eczema / dermatitis, pruritus dermatitis, and atopic dermatitis. It has already been put into practical use as a therapeutic agent for various allergic diseases.

Similarly, olopatadine hydrochloride {11-[(1Z) -3- (Dimethylamino) propylidene] -6,11-dihydrodibenzo [b, e] oxepin-2-yl} acetic acid monohydrochlide also has an antihistamine effect. It has been put to practical use as an anti-allergic drug, an antihistamine drug, and an ophthalmic drug.

In addition, loratadine Ethyl 4- (8-chloro-5,6-dihydr-11H-benzo [5,6] cyclohepta [1,2-b] pyridin-11-ylidene) -1-piperidinecarboxylate is a persistent selection histamine H1. It is used as a receptor antagonist for allergic rhinitis and skin eczema.

A technique has been proposed for the purpose of improving the stability of fexofenadine by granulating particles containing fexofenadine and a binder and preparing them as tablets, and by selecting the binder thereof (Patent Documents). However, it is not known what the granulation property is.

On the other hand, ethanol-insoluble saccharides and polysaccharides, their reduced products, and one or more kinds of gums are commonly used by heating and mixing and dissolving them together with glycyrrhizin (glycyrrhizic acid or a mixture of glycyrrhizic acid and a salt of glycyrrhizic acid). A technique has been proposed that can provide a glycyrrhizin preparation that is easily soluble in water, can be easily granulated or granulated, and does not precipitate even on the acidic side by being dried and powdered by a drying means. (Patent Document 2). However, in the example, in a test using a small granulation tester, it is described that glycyrrhizin alone caused clogging immediately after operation and could not granulate, and glycyrrhizin itself was produced. It was known as a difficult ingredient.

Japanese Unexamined Patent Publication No. 2013-119540 Japanese Unexamined Patent Publication No. 3-14519

There is a need for the development of a drug having good properties as an anti-allergic composition that can be satisfactorily granulated as needed.

The present invention has found for the first time that fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine have poor granulation properties, and as a result of diligent studies focusing on this, surprisingly, fexofenadine hydrochloride and It was found that the granulation property is improved by making a composition containing glycyrrhizic acid and / or a salt thereof, which is considered to be difficult to granulate, and that such a composition has an excellent effect on allergic diseases. , The present invention has been completed.

That is, the present invention
[1]
An antiallergic composition containing (B) glycyrrhizinic acid and / or a salt thereof, which is one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride and loratadine. Stuff;
[2]
The antiallergic composition according to the above [1], which contains (B) glycyrrhizinic acid and / or a salt thereof in a proportion of 0.06 to 2.0 parts by mass with respect to 1 part by mass of (A) fexofenadine hydrochloride. Stuff;
[3]
(A) The antiallergic composition according to the above [1] or the above [2], which contains 60 to 120 mg of fexofenadine hydrochloride as a daily dose;
[4]
(A) The antiallergic composition according to the above [1] or the above [2], which contains 5 to 10 mg of olopatadine hydrochloride as a daily dose;
[5]
(A) The antiallergic composition according to the above [1] or the above [2], which contains 5 to 12 mg of loratadine as a daily dose;
[6]
The antiallergic composition according to any one of the above [1] to [5], wherein the glycyrrhizic acid and / or a salt thereof is derived from a licorice extract or licorice powder.
[7]
(B) The antiallergic composition according to any one of the above [1] to [6], which contains 2 to 220 mg of glycyrrhizic acid and / or a salt thereof as a daily dose;
[8]
The antiallergic composition according to any one of the above [1] to [7], which is a solid agent;
[9]
(B) A method for improving the granulation property of (A) fexofenadine hydrochloride by using glycyrrhizic acid and / or a salt thereof;
[10]
Provided is a method for producing a solid preparation, which comprises blending (A) fexofenadine hydrochloride and (B) glycyrrhizic acid and / or a salt thereof to granulate.

The anti-allergic composition of the present invention has good granulation properties even when made into a solid agent.

FIG. 1 is a diagram showing the distribution of particles obtained by granulating the antiallergic composition of the present invention for each particle size range together with the distribution of particles of a comparative example for each particle size range.

[Anti-allergic composition]
The antiallergic composition of the present invention is an antiallergic agent selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine, and (B) glycyrrhizinic acid and / or a salt thereof. And contains.

(A) Fexofenadine Hydrochloride is a known antiallergic agent, and has an antihistamine action, a mediator release inhibitory action, an inflammatory cytokine release inhibitory action, and an eosinophil migration inhibitory action. Olopatadine hydrochloride and loratazi are also known antiallergic agents with antihistamine activity.
On the other hand, (B) glycyrrhizic acid and / or a salt thereof (hereinafter, glycyrrhizic acid and / or a salt thereof are collectively referred to as glycyrrhizic acids) is known to be effective as a peptic ulcer and an expectorant. It can be obtained as a commercially available product or manufactured by a known manufacturing method. Here, glycyrrhizic acid and / or a salt thereof may be derived from a crude drug. Therefore, the antiallergic composition of the present invention is an antiallergic agent and (B) glycyrrhizinic acid and / or one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine. It may contain a crude drug containing the salt.

In the antiallergic composition of the present invention, (B) glycyrrhizinic acid and / or a salt thereof is an allergic disease having one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine. At the same time, it improves the granulation property of fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine, which are poorly granulated by themselves, and one selected from the group consisting of loratadine and glycyrrhizic acids. You can also let them.

The dose (dose) of (A) fexofenadine hydrochloride according to the antiallergic composition of the present invention depends on the patient's condition (weight, age, symptom, physical condition, etc.) and the agent of the antiallergic composition of the present invention. Although it may vary depending on the shape, etc., it tends to be preferable that the amount is large from the viewpoint of exerting a sufficient effect on allergic diseases, while it tends to be preferable that the amount is small from the viewpoint of suppressing the occurrence of side effects. is there. From the viewpoint of exerting the effect of the present invention more remarkably, the antiallergic composition of the present invention contains fexofenadine hydrochloride, preferably 30 to 240 mg, more preferably 60 to 120 mg, as a daily dose. , More preferably 80 to 120 mg, and particularly preferably 120 mg.

The dose (dose) of (A) olopatadine hydrochloride according to the antiallergic composition of the present invention is the patient's condition (weight, age, symptom, physical condition, etc.), the dosage form of the antiallergic composition of the present invention, etc. Although it may differ depending on the type, a large amount tends to be preferable from the viewpoint of exerting a sufficient effect on allergic diseases, while a small amount tends to be preferable from the viewpoint of suppressing the occurrence of side effects. From the viewpoint of exerting the effect of the present invention more remarkably, the antiallergic composition of the present invention contains olopatadine hydrochloride as a daily dose, preferably 1 to 20 mg, more preferably 2 to 15 mg, and further. It preferably contains 5 to 10 mg, particularly preferably 10 mg.

The dose (dose) of (A) loratadine according to the antiallergic composition of the present invention varies depending on the patient's condition (weight, age, symptom, physical condition, etc.), the dosage form of the antiallergic composition of the present invention, and the like. However, from the viewpoint of exerting a sufficient effect on allergic diseases, the larger amount tends to be preferable, while from the viewpoint of suppressing the occurrence of side effects, the smaller amount tends to be preferable. From the viewpoint of exerting the effect of the present invention more remarkably, the antiallergic composition of the present invention contains loratadine in a daily dose of preferably 1 to 20 mg, more preferably 5 to 15 mg, still more preferably. It contains 5 to 12 mg, particularly preferably 10 mg.

The salt of (B) glycyrrhizic acid is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include sodium salt, ammonium salt, potassium salt, monoammonium salt and the like, and among them, glycyrrhizic acid and Dipotassium glycyrrhizinate is more preferred, and dipotassium glycyrrhizinate is particularly preferred.

(B) Glycyrrhizic acid and / or a salt thereof may be the component itself, or may be contained in crude drugs or Chinese herbal medicines. (B) When glycyrrhizic acid and / or a salt thereof is contained as a crude drug containing them, the crude drug is preferably one or more selected from the group consisting of licorice (licorice) extract and licorice powder. When glycyrrhizic acid and / or its salt is contained as a Chinese herbal medicine containing them, Shoseiryuto, Kakkonto Kagawa Kyushinto, Ryokan Ginger Mishin Natsujinto, Ginger Rensuiyu, Gokoto, Bakumondoto, It is preferable that it is at least one selected from the group consisting of Kakkonto, Maoyu, and Toki-drinking children, and is preferably Shoseiryuto, Kakkonto Kagawa Kyushinto, Ryokan Ginger Mishin Natsujinto, and Gokotoren. It is more preferable that the number is one or more selected from the group consisting of Gokoto, and Shoseiryuto is particularly preferable.

The dose (dose) of (B) glycyrrhizinic acid and / or a salt thereof according to the antiallergic composition of the present invention is the patient's condition (weight, age, symptom, physical condition, etc.) and the antiallergic composition of the present invention. Although it may differ depending on the dosage form of (A), a large amount tends to be preferable from the viewpoint of sufficiently enhancing the effect of the component (A) on allergic diseases, while it is preferable from the viewpoint of suppressing the occurrence of side effects. The smaller the amount, the more preferable.

From the viewpoint of exerting the effect of the present invention more remarkably, the antiallergic composition of the present invention has a total amount of (B) glycyrrhizic acid and / or a salt thereof contained in the composition as a daily dose. , Glycyrrhizic acid is preferably contained in an amount of 2 to 220 mg, more preferably 8.5 to 180 mg, and even more preferably 20 to 100 mg. The amount and ratio of glycyrrhizic acid and / or a salt thereof in the present invention refers to the amount and ratio when converted to glycyrrhizic acid even when it is contained as a salt of glycyrrhizic acid.

The anti-allergic composition of the present invention contains (B) glycyrrhizic acid and / or a salt thereof as a daily dose, and (B) glycyrrhizic acid as a daily dose. And / or a salt thereof, as glycyrrhizic acid, preferably 2 to 220 mg, more preferably 20 to 180 mg, still more preferably 30 to 100 mg, and particularly preferably 40 to 70 mg. When the composition for anti-allergy of the present invention contains a crude drug or a Chinese herbal medicine containing (B) glycyrrhizic acid and / or a salt thereof, (B) glycyrrhizic acid and / or a salt thereof is used as a daily dose. The glycyrrhizic acid is preferably contained in an amount of 2 to 55 mg, more preferably 3 to 30 mg, still more preferably 5 to 26 mg.

When the composition for anti-allergy of the present invention contains licorice powder as a crude drug containing glycyrrhizic acid and / or a salt thereof, the daily dose is preferably 200 as the crude drug equivalent amount of licorice powder. It may contain ~ 2000 mg, more preferably 150-1500 mg, still more preferably 150-820 mg. When licorice extract is included as a crude drug containing glycyrrhizic acid and / or a salt thereof, the daily dose is preferably 500 to 5000 mg, more preferably 600 to 2800 mg, and further preferably 600 to 2800 mg in terms of the crude drug equivalent of licorice. Contains 650 to 2400 mg, particularly preferably 700 to 1500 mg. When a herbal medicine containing glycyrrhizic acid and / or a salt thereof is blended with a herbal medicine containing licorice as a constituent crude drug, the daily dose is preferably 100 to 3500 mg, more preferably 100 to 3500 mg in terms of the crude drug equivalent of licorice. Contains 200 to 3200 mg, more preferably 350 to 3000 mg, and particularly preferably 500 mg.

When the antiallergic composition of the present invention contains licorice extract as a crude drug containing glycyrrhizic acid and / or a salt thereof, the daily dose is preferably 10 to 3000 mg, more preferably 10 to 3000 mg of licorice extract. It may contain 50 to 1500 mg, more preferably 100 to 1000 mg. When a herbal medicine containing glycyrrhizic acid and / or a salt thereof is blended with a herbal medicine containing licorice, the herbal medicine is preferably 100 to 5000 mg, more preferably 300 to 4000 mg, and further preferably 500 to 3000 mg. , Particularly preferably 600 to 2000 mg.

The antiallergic composition of the present invention can be usually administered 1 to 6 times a day, preferably 1 to 3 times a day, most preferably twice a day. Therefore, the anti-allergic composition of the present invention for a single administration preferably contains the above-mentioned daily dose divided by the number of daily administrations. Since the antiallergic composition of the present invention also has a long-lasting effect, a high effect is maintained even if it is administered once or twice a day.

The anti-allergic composition of the present invention has a viewpoint of exerting more remarkable effects of the present invention such as (A) a viewpoint of sufficiently enhancing the effect of fexofenadine hydrochloride on allergic diseases and a viewpoint of improving granulation property. From the viewpoint of cost effectiveness, (B) glycyrrhizinic acid and / or a salt thereof is preferably 0.06 to 2.0 parts by mass, more preferably, with respect to 1 part by mass of (A) fexofenadine hydrochloride. Is contained in an amount of 0.15 to 1.7 parts by mass, more preferably 0.2 to 1.5 parts by mass, and particularly preferably 0.3 to 0.6 parts by mass.

Further, the antiallergic composition of the present invention is a book from the viewpoint of (A) sufficiently enhancing the effect on one allergic disease selected from the group consisting of olopatadine hydrochloride and loratadine, and improving the granulation property. From the viewpoint of exerting the effect of the present invention more remarkably and from the viewpoint of cost effectiveness, (B) glycyrrhizic acid and (B) glycyrrhizinic acid and 1 part by mass selected from the group consisting of (A) olopatadine hydrochloride and loratadine. / Or a salt thereof, preferably 0.6 to 30.0 parts by mass, more preferably 1.5 to 20.0 parts by mass, still more preferably 2.0 to 15.0 parts by mass, particularly preferably 3.0. Contains ~ 10.0 parts by mass.

(B) When citrus powder or kanzo extract is contained as a crude drug containing glycyrrhizic acid and / or a salt thereof, or when a herbal medicine containing glycyrrhizic acid and / or a salt thereof is added to a constituent crude drug. The anti-allergic composition of the present invention exerts the effects of the present invention more remarkably from the viewpoint of (A) sufficiently enhancing the effect of fexofenadine hydrochloride on allergic diseases and improving the granulation property. From the viewpoint of (A) fexofenadine hydrochloride and 1 part by mass of (B) glycyrrhizic acid and / or a salt thereof, a crude drug or a Chinese herbal medicine containing (B) glycyrrhizic acid and / or a salt thereof is preferably 0.5 to 50 mass by mass. Parts, more preferably 0.8 to 35 parts by mass, still more preferably 2 to 15 parts by mass. Alternatively, the amount of licorice in terms of crude drug is preferably 1 to 100 parts by mass, more preferably 3 to 50 parts by mass, and further preferably 6 to 20 parts by mass.

(B) When licorice powder or licorice extract is contained as a crude drug containing glycyrrhizic acid and / or a salt thereof, or when a herbal medicine containing glycyrrhizic acid and / or a salt thereof is added to a constituent crude drug. The anti-allergic composition of the present invention has (A) a viewpoint of sufficiently enhancing the effect on one kind of allergic disease selected from the group consisting of olopatadine hydrochloride and loratadine, a viewpoint of improving granulation property, and the like. From the viewpoint of exerting the effect of the present invention more remarkably and from the viewpoint of cost effectiveness, (B) glycyrrhizic acid and / / with respect to 1 part by mass of one selected from the group consisting of (A) olopatadine hydrochloride and loratazine. Alternatively, a crude drug or a Chinese herbal medicine containing a salt thereof is preferably contained in an amount of 5 to 1000 parts by mass, more preferably 10 to 500 parts by mass, and further preferably 20 to 100 parts by mass. Alternatively, the amount of licorice in terms of crude drug is preferably 5 to 1000 parts by mass, more preferably 20 to 500 parts by mass, and further preferably 50 to 200 parts by mass.

The anti-allergic composition of the present invention contains fexofenadine hydrochloride (30-240 mg) and glycyrrhizic acid as daily doses from the viewpoint of high effect on allergic diseases and low side effects (eg, drowsiness). And / or a salt thereof is preferably contained in an amount of 2 to 220 mg, fexofenadine hydrochloride is preferably contained in an amount of 60 to 120 mg, and fexofenadine hydrochloride and / or a salt thereof is preferably contained in an amount of 8.5 to 180 mg. It is more preferable to contain 80 to 120 mg of salt and 20 to 100 mg of glycyrrhizic acid and / or a salt thereof.

From the viewpoint of high effect on allergic diseases and low side effects (eg, drowsiness, etc.), the antiallergic composition of the present invention contains 1 to 20 mg of olopatadine hydrochloride and glycyrrhizic acid and / / as the daily dose. Alternatively, it preferably contains 2 to 220 mg of olopatadine hydrochloride, more preferably 2 to 15 mg of olopatadine hydrochloride, and 8.5 to 180 mg of glycyrrhizic acid and / or a salt thereof, and 5 to 10 mg of olopatadine hydrochloride. And it is more preferable to contain 20 to 100 mg of glycyrrhizic acid and / or a salt thereof.

From the viewpoint of high effect on allergic diseases and low side effects (eg, drowsiness, etc.), the antiallergic composition of the present invention contains 1 to 20 mg of loratadine and / or glycyrrhizic acid as a daily dose. It preferably contains 2 to 220 mg of salt, 5 to 15 mg of loratadine, and 8.5 to 180 mg of glycyrrhizic acid and / or a salt thereof, 5 to 12 mg of loratadine, and glycyrrhizic acid and / or. It is more preferable to contain 20 to 100 mg of the salt.

The anti-allergic composition of the present invention preferably further contains the following (C) binder from the viewpoint of exerting the effect of the present invention of satisfactorily granulating. The (C) binder that can be contained in the anti-allergic composition of the present invention is not limited, and may be a poorly water-soluble binder (crystalline cellulose, low-degree-of-substitution hydroxypropyl cellulose), etc. preferable. In particular, when the anti-allergic composition of the present invention is a composition that has undergone a granulation process, a water-soluble binder is preferable. The water-soluble binder that can be contained in the anti-allergic composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically or physiologically acceptable, and is a polysaccharide, a protein, or a water-soluble cellulose. It may be any of a polymer, starch, water-soluble vinyl polymer, polyether, and saccharide. Here, specific examples of the polysaccharide include arabic gum, agar, traganth gum, sodium alginate, carrageenan, xanthan gum, guar gum, dextran, pullulan, pectin, chitosan, hemilose and the like. Specific examples of the protein include gelatin, purified gelatin and the like. Specific examples of the water-soluble cellulose-based polymer include carmellose or a salt thereof, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, hydroxyethyl cellulose and the like. Specific examples of starches include starch (wheat starch, corn starch, potato starch, etc.), pregelatinized starch, dextrin, cyclodextrin, carboxymethyl starch, hydroxypropyl starch, hydroxyethyl starch, partially pregelatinized starch, and the like. Be done. Specific examples of the water-soluble vinyl polymer include polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, and copolydone. Examples of the acrylic polymer include sodium polyacrylate and the like. Specific examples of the polyethers include macrogol and the like. Specific examples of the sugar include syrup starch syrup, fructose, sugar alcohols (for example, xylitol and sorbitol), glucose and the like. The pharmaceutical use of these components (C) may be other than the binder. Among the above binders, cellulosic polymers such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose and methyl cellulose; starches such as potato starch, corn starch and pregelatinized starch; and vinyl polymers composed of polyvinylpyrrolidone and polyvinyl alcohol. It is preferable that the binder is a water-soluble polymer (also referred to as a water-soluble binder in the present specification), and hydroxypropyl cellulose and polyvinylpyrrolidone are more preferable.

When the antiallergic composition of the present invention contains (C) a binder, the effect on one allergic disease selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine. (A) Fexofenadine Hydrochloride, Olopatadine Hydrochloride, and The binder (C) is preferably 0.03 to 2.0 parts by mass, more preferably 0.05 to 1.7 parts by mass, still more preferably, with respect to 1 part by mass of 1 type selected from the group consisting of loratadine. Contains 0.08 to 1.5 parts by mass. Since the anti-allergic composition of the present invention has improved granulation properties, it has good granulation properties even with a small amount of binder.

The anti-allergic composition of the present invention is optionally selected from the group consisting of fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine, and glycyrrhizinic acid and / or a salt thereof, as well as other physiological activities. Ingredients may be included.
Examples of such physiologically active components include (1) parasympathetic blockers (eg, atropine, scopolamine, belladonna total alkaloids, isopropamide iodide, datura extract, scopolia extract, etc.), and (2) sympathetic excitatory components (eg, pseudoephedrine). , Methylephedrine, phenilefrine, phenylpropanolamine, ephedrine, etilefrine, methoxamine, midodrine, methoxyphenamine, etc.),
(3) Anti-inflammatory enzymes (for example, lysozyme, serratiopeptidase, bromelain, pronase, etc.)
(4) Crude drugs and ingredients derived from crude drugs (for example, ginger, carrot, maou, keihi, schizonepeta, saishin, shinii, nantenjitsu, ohi, biakushi, zenko, kikyo, shazenshi, goou, zedoary, biakujutsu, sojutsu, gentiana, fennel , Onji, Oubaku, Coptis chinensis, Phellodendron amur, Chinpi, Chouji, Senega, Ginger, Shajin, etc.),
(5) Xanthine derivatives (for example, caffeine, theophylline, aminophylline, theobromine, diprofayrin, proxifylline, pentoxifylline, etc.),
(6) Antitussive analgesic ingredients (eg, aspirin, aspirin aluminum, acetaminophen, ethenzamide, sazapyrin, salicylamide, sodium salicylate, lactylphenetidine, ibuprofen, ketoprofen, etc.), (7) Antitussive ingredients (eg, achloramide, Cloperastin, pentoxiberin (carbetapentan), tipepidin, dibunate, dextrometolphan, codeine, dihydrocodeine, noscapin, etc.),
(8) Expectorants (eg, potassium guaiacol sulfonate, guaifenesin, etc.),
(9) Vitamins (for example, vitamin A [for example, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene, etc.], vitamin Bs [for example, thiamine, thiamine disulfide, disetiamine, octothiamine, sicothamine, bisive Thiamine, Bisbenchamine, Prosultiamine, Benfothamine, Flusultiamine, Riboflavin, Flavin Adenin Dinucleotide, Pyridoxin, Pyridoxal, Hydroxokobalamine, Cyanocobalamine, Methylcobalamine, Deoxyadecobalamine, Folic acid, Tetrahydrofolic acid, Dihydrofolic acid, Nicotin Acids, nicotinic acid amide, nicotinyl alcohol, pantothenic acid, pantenol, biotin, choline, inositol, etc.], vitamin Cs [eg, ascorbic acid, erythorbic acid, or derivatives thereof], vitamin Ds [eg, ergocalci Ferrol, chorecalciferol, hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotaxterol, etc.], vitamin Es [eg, tocopherol and its derivatives, ubiquinone derivatives, etc.], and other vitamins [eg, hesperidin, carnitine, ferula, etc.] Acids, γ-orizanol, orotic acid, rutin, eriocitrin, etc.], and (10) Mucosal protective components (eg, aminoacetic acid, dry aluminum hydroxide gel, aluminum-based mucosal protective agents such as dihydroxyaluminum / aminoacetate) ; Magnesium aluminometasilicate, aluminum silicate, hydrotalcite, aluminum hydroxide magnesium hydroxide, aluminum hydroxide gel, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, aluminum hydroxide / magnesium carbonate mixed dry gel, hydroxide Co-precipitated products of aluminum / calcium carbonate / magnesium carbonate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium silicate, magnesium hydroxide-based mucosal protective agents such as co-precipitated products of magnesium hydroxide / aluminum potassium sulfate) Can be mentioned.
These bioactive ingredients may be free or salts.

The anti-allergic composition of the present invention is preferably an orally administered composition. Its dosage form includes tablets (including quick-disintegrating tablets in the oral cavity, chewable tablets, effervescent tablets, jelly-like drop agents, etc.), troches, granules, pills, dry syrups, and powders (including fine granules). ), Capsules (including hard capsules and soft capsules), as well as liquids, suspending agents, emulsions, syrups, elixirs, limonades, tinctures, extracts, jellies, gels. Examples thereof include agents and liposome agents. Among them, one selected from the group consisting of fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine from the viewpoint of further exerting the effect of the present invention and versatility, glycyrrhizic acid and / or its A solid agent containing a salt is preferable, and a solid agent prepared through granulation is particularly preferable. Solid preparations prepared through granulation include granules, tablets, lozenges, hard capsules, dry syrups and the like. Of these, tablets or granules prepared through granulation are particularly preferable.

When the anti-allergic composition of the present invention is a tablet, granule, or hard capsule, the content of fexofenadine hydrochloride with respect to the total amount of the solid preparation is determined from the viewpoint of exerting the effect of the present invention more remarkably. , Usually 2.5 to 35 w / w%, preferably 10 to 25 w / w%, preferably 13 to 20 w / w%, and even more preferably 13 to 18 w / w%. Further, when the antiallergic composition of the present invention is a tablet, granule, or hard capsule, from the viewpoint of exerting the effect of the present invention more remarkably, from olopatadine hydrochloride and loratadine with respect to the total amount of the solid preparation. The content of one selected from the group is usually 0.05 to 3.5 w / w%, preferably 0.1 to 2.0 w / w%, and more preferably 0.3 to 1.5 w / w. %.

When the anti-allergic composition of the present invention is a tablet, granule, or hard capsule, the content of glycyrrhizic acid and / or a salt thereof with respect to the total amount of the solid preparation is contained from the viewpoint of exerting the effect of the present invention more remarkably. The amount is usually 0.03 to 57.0 w / w%, preferably 0.5 to 30 w / w%, and more preferably 1 to 20 w / w%. When a crude drug or a Chinese herbal extract is used as the glycyrrhizic acid and / or its salt, the content of the glycyrrhizic acid and / or its salt with respect to the total amount of the solid preparation is preferably 15 to 50 w / w%.

When the anti-allergic composition of the present invention is a tablet, granule, or hard capsule, the solid content of the (C) binder with respect to the total amount of the solid agent is contained from the viewpoint of exerting the effect of the present invention more remarkably. The amount is preferably 0.5 w / w% to 90 w / w%, more preferably 0.5 to 50 w / w%, further preferably 1 to 30 w / w%, and most preferably 10 to 20 w / w%. Is.

The (C) binder here is not limited, but is preferably (C) a water-soluble binder. The anti-allergic composition of the present invention remarkably exerts the effect of the present invention by containing (C) a water-soluble binder having an appropriate mass with respect to the total mass of the granulated product or the composition.

Further, the anti-allergic composition of the present invention may contain an appropriate additive depending on its dosage form. Such additives include, in the case of solid preparations (eg, tablets, capsules, powders, etc.), excipients (eg, sucrose, lactose, crystalline cellulose, light anhydrous silicic acid, etc.), lubricants (eg, sucrose anhydride, etc.). , Sucrose fatty acid ester, magnesium stearate, talc, etc.), disintegrant (eg, low-substituted hydroxypropyl cellulose, crospovidone, croscarmellose sodium, etc.), foaming agent (eg, sodium hydrogen carbonate, etc.), fluidizing agent (For example, sodium aluminate metasilicate, light anhydrous silicic acid, etc.), and the like. The pharmaceutical uses of these additives may be other than the above. In the case of liquid preparations (for example, syrups, liquids, suspending agents, soft capsule contents, hard capsule contents such as liquid ones), oil-based bases (for example, olive oil, corn oil, etc.) Vegetable oils such as soybean oil, sesame oil, cottonseed oil; medium chain fatty acid triglycerides, etc.), aqueous bases (eg, Macrogol 400, water), gel bases (eg, carboxyvinyl polymers, gums, etc.), surfactants (eg, carboxyvinyl polymers, gums, etc.) , Polysolvate 80, hardened castor oil, glycerin fatty acid ester, sorbitan sesquioleate, etc.), suspending agents (eg, sala mitsuro, various surfactants, soy lecithin, etc.), dispersants, emulsifiers, stabilizers, buffers , Dissolving aids, pH adjusters, preservatives (preservatives) and the like. Further, in any case, antioxidants, sweeteners, acidulants, colorants, flavors, flavoring agents and the like may be appropriately added to these compositions.

The anti-allergic composition of the present invention comprises fexofenadine hydrochloride, glycyrrhizic acid and / or a salt thereof, and other physiologically active ingredients and additives used as desired, depending on the dosage form. Can be obtained by formulating.

In addition, the anti-allergic composition of the present invention has allergic rhinitis (perennial allergic rhinitis and seasonal allergic rhinitis) caused by allergens such as mites, house dust, and pollen as symptoms. (Including symptoms)) or urticaria, and pruritus associated with skin diseases such as eczema / dermatitis, pruritus dermatitis, and atopic dermatitis are highly effective. The anti-allergic composition of the present invention is particularly useful for reducing allergic symptoms in patients with allergic rhinitis. In particular, by containing one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine and (B) glycyrrhizinic acid and / or a salt thereof, sneezing, runny nose, nasal congestion, etc. Relieves allergic symptoms of the nose.

The antiallergic composition of the present invention is obtained by simultaneously formulating one selected from the group consisting of fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine with glycyrrhizic acid and / or a salt thereof. It may be a preparation, or it may be a combination of two kinds of preparations obtained by separately formulating, but it is preferably prepared as a single preparation.

The present invention is an antiallergic composition containing (B) glycyrrhizic acid and / or a salt thereof and one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine. Regarding things.

The anti-allergic composition contains (A) fexofenadine hydrochloride, olopatadine hydrochloride, and one selected from the group consisting of loratadine, and (B) glycyrrhizinic acid and / or a salt thereof. The anti-allergic effect is enhanced, and it has a remarkable therapeutic and / or preventive effect on allergic diseases and symptoms. In particular, allergic rhinitis caused by allergens such as mites, house dust, and pollen (including perennial allergic rhinitis and seasonal allergic rhinitis (such as nasal inflammation of pollinosis)) or urticaria, and It is effective for pruritus associated with skin diseases such as eczema / dermatitis, pruritus dermatitis, and atopic dermatitis.

The antiallergic composition preferably contains (B) glycyrrhizinic acid and / or a salt thereof in a ratio of 0.06 to 2.0 parts by mass with respect to 1 part by mass of (A) fexofenadine hydrochloride. , Particularly preferably, it is contained in a proportion of 0.07 to 1.5 parts by weight.

The antiallergic composition contains 0.6 to 30 parts by mass of (B) glycyrrhizinic acid and / or a salt thereof with respect to 1 part by mass of one selected from the group consisting of (A) olopatadine hydrochloride and loratadine. It is preferable to contain it in a proportion of 1.5 to 20 parts by weight, and it is particularly preferable to contain it in a proportion of 1.5 to 20 parts by weight.

The anti-allergic composition may contain (A) fexofenadine hydrochloride in a daily dose of 60 to 120 mg.

The anti-allergic composition may contain (A) olopatadine hydrochloride in an amount of 5 to 10 mg per day.

The anti-allergic composition may contain (A) loratadine in a daily dose of 5-12 mg.

The anti-allergic composition may contain (B) glycyrrhizic acid and / or a salt thereof in an amount of 2 to 220 mg per day.

The anti-allergic composition preferably further contains (C) a binder.

The binder (C) is one or more water-soluble binders selected from polysaccharides, proteins, water-soluble cellulosic polymers, starches, water-soluble vinyl polymers, polyethers, and saccharides. Is preferable.

Among the above binders, cellulosic polymers such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose and methyl cellulose; starches such as potato starch, corn starch and pregelatinized starch; and vinyl polymers composed of polyvinylpyrrolidone and polyvinyl alcohol. It is preferable to contain a more selected water-soluble polymer binder.

The anti-allergic composition can be a solid agent.

The solid agent is particularly preferably a solid agent prepared through granulation.

The solid preparation is preferably a tablet, granule, or hard capsule prepared through granulation.
[A method for improving granulation property of one selected from the group consisting of fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine]
The present invention is also a method for improving the granulation property of one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine by (B) glycyrrhizinic acid and / or a salt thereof. Also related. For example, the antiallergic composition of the present invention coexists with (B) glycyrrhizinic acid and / or a salt thereof and one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine. By doing so, good granulation property can be imparted to the antiallergic composition. Here, "improving granulation property" and "providing good granulation property" can be used in the same meaning, and are composed of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine. It means that it is better than the granulation property of one kind selected from the group alone. For example, the proportion of fine particles in the whole is smaller and the value of median diameter D50 is higher than when granulated by one selected from the group consisting of fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine alone. It means things such as. Although not particularly limited, it can be said that the smaller the ratio of the weight of the fine particles to the total weight, the better, but it is preferably at least 20% or less of the total weight. Also in this method, the amount of (B) glycyrrhizinic acid and / or a salt thereof, the amount of one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine, and the optional component (C). ) The amount of binders and their component ratios are the same as in the case of antiallergic compositions.

[Manufacturing method of solid preparation]
The present invention also comprises blending (B) glycyrrhizic acid and / or a salt thereof with one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine, and granulating. It depends on the method for producing a characteristic solid preparation. Also in this method, the amount of (B) glycyrrhizinic acid and / or a salt thereof, the amount of one selected from the group consisting of (A) fexofenadine hydrochloride, olopatadine hydrochloride, and loratadine, and the optional component (C). ) The amount of binders and their component ratios are the same as in the case of antiallergic compositions.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto.

Example 1
Based on the formulation table shown in Table 1, 144 g of fexofenadine hydrochloride, 60 g of dipotassium glycyrrhizinate, 264 g of lactose hydrate, 108 g of partially pregelatinized starch, and crystalline cellulose were added to a fluidized bed granulator (LAB-1, Paulec). 96 g of the mixture was charged. Under the conditions of an intake air temperature setting of 75 ° C. and an air volume of 30 to 50 m ³ / h, 600 g of a 5% polyvinylpyrrolidone aqueous solution was sprayed therein, and the mixture was dried to obtain granules. 10 g of the obtained granules were classified using sieves of six different sieves of 500, 355, 250, 150, 106 and 75 μm, and the weight remaining on the sieve was measured. From each weight, the ratio of the weight of the amount of fine powder of 106 μm or less to the whole was calculated. Further, the median diameter D50, which is the diameter corresponding to the 50% cumulative value of these cumulative distribution curves, was calculated based on a fixed method.

Comparative Example 1
Based on the formulation table shown in Table 1, a mixture of fexofenadine hydrochloride 144 g, lactose hydrate 324 g, partially pregelatinized starch 108 g, and crystalline cellulose 96 g was charged into a fluidized bed granulator (LAB-1, Paulec). .. Under the condition that the intake air temperature was set to 75 ° C. and the air volume was 30 to 50 m ³ / h, 600 g of a 5% polyvinylpyrrolidone aqueous solution was sprayed therein, and the mixture was dried to obtain granules. By the same method as in Example 1, the weight ratio of the amount of fine powder of 106 μm or less and the median diameter D50 were determined.

Table 1 shows the results of studies on improving the granulation properties of Example 1 and Comparative Example 1 (reducing the proportion of fine powder and increasing the median diameter D50).

In Comparative Example 1, the amount of powder (fine powder) of 106 μm or less accounted for 38.7% of the total, whereas in Example 1, the amount of powder of 106 μm or less was 18.6% of the total. That is, it can be seen that by blending glycyrrhizic acids with fexofenadine hydrochloride, the amount of fine powder is reduced to less than half even though the entire composition contains the same amount of water-soluble binder. It was also obvious that the granules prepared in Comparative Example 1 were more scattered to the surroundings and adhered to the equipment than the granules prepared in Example 1.

Further, in Comparative Example 1, the median diameter D50 was 108.6 μm, whereas in Example 1, the median diameter D50 was 150.2 μm. From this, it was shown that the median diameter of the granules surely obtained by granulating with fexofenadine hydrochloride and glycyrrhizic acid was large, and there was an effect of increasing the particle size.

Further, the distribution for each particle size range is shown in FIG. It is clear that the proportion of particles having a particle size of 150 μm or less is larger in Comparative Example 1 than in Example 1, and in particular, it can be seen that the amount of fine particles of 106 μm or less in the formulation of Comparative Example 1 is larger than that in Example 1.

Example 2
Based on the formulation table shown in Table 2, fexofenadine hydrochloride 144 g, dipotassium glycyrrhizinate 24 g, lactose hydrate 324 g, partially pregelatinized starch 108 g, crystalline cellulose was added to a fluidized bed granulator (LAB-1, Paulec). 96 g of the mixture was charged. Under the conditions of an intake air temperature setting of 75 ° C. and an air volume of 30 to 50 m ³ / h, 600 g of a 5% polyvinylpyrrolidone aqueous solution was sprayed therein, and the mixture was dried to obtain granules. By the same method as in Example 1, the weight ratio of the amount of fine powder of 106 μm or less and the median diameter D50 were determined.

Example 3
Based on the formulation table shown in Table 2, fexofenadine hydrochloride 144 g, dipotassium glycyrrhizinate 216 g, lactose hydrate 324 g, partially pregelatinized starch 108 g, crystalline cellulose was added to a fluidized bed granulator (LAB-1, Paulec). 96 g of the mixture was charged. Under the conditions of an intake air temperature setting of 75 ° C. and an air volume of 30 to 50 m ³ / h, 600 g of a 5% polyvinylpyrrolidone aqueous solution was sprayed therein, and the mixture was dried to obtain granules. By the same method as in Example 1, the weight ratio of the amount of fine powder of 106 μm or less and the median diameter D50 were determined.

As shown in Table 2, as a result of granulating in the same manner as in Example 1 by changing the amount of glycyrrhizic acid added, the median diameter D50 was 172.5 μm in Example 2 and 165.0 μm in Example 3. It was clarified that a small amount of glycyrrhizic acid has almost the same effect regardless of the amount of glycyrrhizic acid added.

Comparing the results of Example 3 in Table 2 and Comparative Example 1 in Table 1, it was possible to realize better granulation in Example 3 even though the ratio of the water-soluble binder to the whole was smaller. In view of the above, it can be interpreted that the addition of glycyrrhizic acid promotes the progress of granulation and enables granulation even with a small amount of binder.

Example 4
Based on the prescription table shown in Table 3, 192 g of fexofenadine hydrochloride, 160 g of licorice extract (700 mg of licorice crude drug equivalent), 24 g of light anhydrous silicic acid, D in a fluidized layer granulator (MP-01D, Paulec). -A mixture of 160 g of mannitol and 320 g of crystalline cellulose was added. 180 g of a 5% hydroxypropyl cellulose aqueous solution was sprayed therein under the conditions of an intake air temperature setting of 70 ° C. and an air volume of 0.2 to 0.6 m ^{3 / min, and dried to obtain granules.} 10 g of the obtained granules were classified using sieves of six different sieves of 500, 355, 250, 150, 106 and 75 μm, and the weight remaining on the sieve was measured. From each weight, the ratio of the weight of the amount of fine powder of 106 μm or less to the whole was calculated. Further, the median diameter D50, which is the diameter corresponding to the 50% cumulative value of these cumulative distribution curves, was calculated based on a fixed method.

Comparative Example 2
Based on the formulation table shown in Table 3, a mixture of fexofenadine hydrochloride 228 g, light anhydrous silicic acid 28.5 g, D-mannitol 190 g, and crystalline cellulose 380 g was added to a fluidized bed granulator (MP-01D, Paulec). did. Under the conditions of an intake air temperature setting of 70 ° C. and an air volume of 0.2 to 0.6 m ³ / min, 184 g of a 5% hydroxypropyl cellulose aqueous solution was sprayed therein, and the mixture was dried to obtain granules. 10 g of the obtained granules were classified using sieves of six different sieves of 500, 355, 250, 150, 106 and 75 μm, and the weight remaining on the sieve was measured. From each weight, the ratio of the weight of the amount of fine powder of 106 μm or less to the whole was calculated. Further, the median diameter D50, which is the diameter corresponding to the 50% cumulative value of these cumulative distribution curves, was calculated based on a fixed method.

Table 3 shows the results of studies on improving the granulation property of Example 4 (reducing the proportion of fine powder and increasing the median diameter D50).

In Comparative Example 2, the amount of powder (fine powder) of 106 μm or less accounted for 88.8% of the total, whereas in Example 4, the amount of powder of 106 μm or less was 18.6% of the total. In other words, it can be seen that the amount of fine powder is reduced to less than half by adding licorice extract to fexofenadine hydrochloride. It was also obvious that the granules prepared in Comparative Example 2 were more scattered to the surroundings and adhered to the equipment than the granules prepared in Examples 4 to 6.

Further, in Comparative Example 2, the median diameter D50 was 55.4 μm, whereas in Examples 4 to 6, the median diameter D50 was 153.2 μm. From this, it was shown that the median diameter of the granules surely obtained by granulating with fexofenadine hydrochloride and licorice was increased, and that there was an effect of increasing the particle size.

Example 5
Based on the prescription table shown in Table 4, a fluidized bed granulator (MP-01D, Paulec) contains 74.4 g of fexofenadine hydrochloride, 496 g of shoseiryuto extract (615 mg of licorice crude drug equivalent), and metasilicic acid. A mixture of 135 g of magnesium aluminate, 62.0 g of lactose hydrate, and 124 g of crystalline cellulose was added. Under the conditions of an intake air temperature setting of 65 ° C. and an air volume of 0.1 to 0.5 m ³ / min, 210 g of a 7% hydroxypropyl cellulose aqueous solution was sprayed therein, and the mixture was dried to obtain granules. A median having a diameter corresponding to 50% of the cumulative distribution curve using a laser diffraction type particle size distribution measuring device (LDSA-3400A particle size distribution measuring device, manufactured by Tonichi Computer Applications Co., Ltd., measuring range: 0.5 to 355 μm). The diameter D50 was determined.

Comparative Example 3
Based on the formulation table shown in Table 4, a mixture of fexofenadine hydrochloride 180 g, magnesium aluminometasilicate 203 g, lactose hydrate 150 g, and crystalline cellulose 300 g was added to a fluidized bed granulator (MP-01D, Paulec). did. Under the conditions of an intake air temperature setting of 65 ° C. and an air volume of 0.1 to 0.5 m ³ / min, 313 g of a 7% hydroxypropyl cellulose aqueous solution was sprayed therein, and the mixture was dried to obtain a powder. A median having a diameter corresponding to 50% of the cumulative distribution curve using a laser diffraction type particle size distribution measuring device (LDSA-3400A particle size distribution measuring device, manufactured by Tonichi Computer Applications Co., Ltd., measuring range: 0.5 to 355 μm). The diameter D50 was determined.

Table 4 shows the results of examination for improving the granulation property of Example 5 (increasing the median diameter D50).

In Comparative Example 3, the median diameter D50 was 15.5 μm, whereas in Example 5, the median diameter D50 was 126.5 μm. From this, it was shown that the median diameter of the granules surely obtained by granulating with fexofenadine hydrochloride and shoseiryuto was large, and that there was an effect of increasing the particle size.

Example 6
Based on the formulation table shown in Table 5, olopatadine hydrochloride 7.5 g, dipotassium glycyrrhizinate 75.0 g, lactose hydrate 330 g, partially pregelatinized starch 135 g, in a fluidized bed granulator (MP-01D, Paulec), A mixture of 120 g of crystalline cellulose was added. 180 g of a 5% polyvinylpyrrolidone aqueous solution was sprayed therein under the conditions of an intake air temperature setting of 75 ° C. and an air volume of 0.1 to 0.7 m ^{3 / min, and dried to obtain granules.} 10 g of the obtained granules were classified using sieves of six different sieves of 500, 355, 250, 150, 106 and 75 μm, and the weight remaining on the sieve was measured. From each weight, the ratio of the weight of the amount of fine powder of 106 μm or less to the whole was calculated. Further, the median diameter D50, which is the diameter corresponding to the 50% cumulative value of these cumulative distribution curves, was calculated based on a fixed method.

Comparative Example 4
Based on the formulation table shown in Table 5, a mixture of 7.5 g of olopatadine hydrochloride, 405 g of lactose hydrate, 135 g of partially pregelatinized starch, and 120 g of crystalline cellulose was added to a fluidized bed granulator (MP-01D, Paulec). .. 180 g of a 5% polyvinylpyrrolidone aqueous solution was sprayed therein under the conditions of an intake air temperature setting of 75 ° C. and an air volume of 0.1 to 0.7 m ^{3 / min, and dried to obtain granules.} 10 g of the obtained granules were classified using sieves of six different sieves of 500, 355, 250, 150, 106 and 75 μm, and the weight remaining on the sieve was measured. From each weight, the ratio of the weight of the amount of fine powder of 106 μm or less to the whole was calculated. Further, the median diameter D50, which is the diameter corresponding to the 50% cumulative value of these cumulative distribution curves, was calculated based on a fixed method.

Table 5 shows the results of studies on improving the granulation property of Example 6 (reducing the proportion of fine powder and increasing the median diameter D50).

In Comparative Example 4, the amount of powder (fine powder) of 106 μm or less accounted for 26.4% of the total, whereas in Example 6, the amount of powder of 106 μm or less was 16.2% of the total. That is, it can be seen that the amount of fine powder is reduced by adding dipotassium glycyrrhizinate to olopatadine hydrochloride. It was also obvious that the granules prepared in Comparative Example 4 were more scattered around and adhered to the equipment than the granules prepared in Example 6.

Further, in Comparative Example 4, the median diameter D50 was 123.5 μm, whereas in Example 6, the median diameter D50 was 180.8 μm. From this, it was shown that the median diameter of the granules surely obtained by granulating both olopatadine hydrochloride and dipotassium glycyrrhizinate was large, and that there was an effect of increasing the particle size.

(Formulation Example) Based on the amounts of Formulation Examples 1 and 2, wet granulation and then tableting were performed to prepare 165 mg tablets per tablet, and 2 tablets were taken per day. Based on the amounts of Formulation Examples 3 to 9, wet granulation and then tableting were performed to prepare 330 mg tablets per tablet, and 2 tablets were taken per day. In addition, 165 mg tablets per tablet were also prepared, and 4 tablets were taken per day. Based on the amounts of Formulation Examples 10 to 12, wet granulation and then tableting were performed to prepare 420 mg tablets per tablet, and 2 tablets were taken per day. In addition, 210 mg tablets per tablet were also prepared, and 4 tablets were taken per day.

Based on the amount of Formulation Example 13, the tablets were directly tableted to prepare 150 mg tablets per tablet, and 2 tablets were taken per day. Based on the amount of Formulation Example 14, the tablets were directly tableted to prepare 165 mg tablets per tablet, and 2 tablets were taken per day. Based on the doses of Formulation Examples 15 to 16, direct tableting was performed to prepare 330 mg tablets per tablet, and 2 tablets were taken per day. Based on the amount of Formulation Example 17, the tablets were directly tableted to prepare 420 mg tablets per tablet, and 2 tablets were taken per day. Based on the amount of Formulation Example 18, dry granulation and then tableting were performed to prepare 150 mg tablets per tablet, and 2 tablets were taken per day. Based on the amount of Formulation Example 19, dry granulation and then tableting were performed to prepare 165 mg tablets per tablet, and 2 tablets were taken per day. Based on the amounts of Formulation Examples 20 to 21, dry granulation and then tableting were performed to prepare 330 mg tablets per tablet, and 2 tablets were taken per day. Based on the amount of Formulation Example 22, dry granulation and then tableting were performed to prepare 420 mg tablets per tablet, and 2 tablets were taken per day.

Based on the amounts of Formulation Examples 23, 24, 26, and 30, 410 mg tablets were prepared per tablet, and 4 tablets were taken per day. Based on the amounts of Formulation Examples 27 and 31, 410 mg tablets were prepared per tablet, and 6 tablets were taken per day. Based on the amounts of Formulation Examples 25, 28, and 29, 410 mg tablets were prepared per tablet, and 8 tablets were taken per day. Based on the amounts of Formulation Examples 32 and 33, 410 mg tablets per tablet were prepared, and 10 tablets were taken per day. Based on the amount of Formulation Example 34, 410 mg tablets per tablet were prepared, and 12 tablets were taken per day. In Formulation Examples 23 to 25, licorice extract having a yield of 15% was used. In Formulation Examples 30 to 34, in order to obtain 1 g of Shoseiryuto extract, Shoseiryuto extract using 750 mg of licorice in terms of crude drug was used.

Based on the amount of Formulation Examples 35-40, 350 mg of granules were prepared per packet, and 2 packets were taken per day. Based on the amount of Formulation Examples 41 to 45, 400 mg of granules were prepared per packet, and 2 packets were taken per day. Based on the amount of Formulation Example 46, 450 mg of granules were prepared per packet, and 2 packets were taken per day. Based on the amount of Formulation Examples 35 to 46, the obtained granules were encapsulated in a hard capsule in the same amount as the amount per packet according to a conventional method, and 2 capsules were taken per day.

Based on the amounts of Formulation Examples 47 to 51, wet granulation and then tableting were performed to prepare a chewable agent of 400 mg per tablet, and 2 tablets were taken per day. In addition, 200 mg of chewable agent was prepared per tablet, and 4 tablets were taken per day.

Based on the doses of Formulation Examples 52 to 54, 260 mg of soft capsules were prepared per tablet, and 2 tablets were taken per day. Based on the amount of Formulation Examples 55 to 59, 260 mg of soft capsules were prepared per tablet, and 4 tablets were taken per day.

(Formulation Example) Based on the amounts of Formulation Examples 60 to 61, wet granulation and then tableting were performed to prepare 165 mg tablets per tablet, and 2 tablets were taken per day. Based on the amounts of Formulation Examples 62 to 68, wet granulation and then tableting were performed to prepare 330 mg tablets per tablet, and 2 tablets were taken per day. In addition, 165 mg tablets per tablet were also prepared, and 4 tablets were taken per day. Based on the amounts of Formulation Examples 69 to 71, wet granulation and then tableting were performed to prepare 420 mg tablets per tablet, and 2 tablets were taken per day. In addition, 210 mg tablets per tablet were also prepared, and 4 tablets were taken per day.

Based on the amounts of Formulation Examples 72, 73, 75, and 79, 410 mg tablets per tablet were prepared, and 4 tablets were taken per day. Based on the amounts of Formulation Examples 76 and 80, 410 mg tablets per tablet were prepared, and 6 tablets were taken per day. Based on the amounts of Formulation Examples 74, 77, and 78, 410 mg tablets per tablet were prepared, and 8 tablets were taken per day. Based on the amounts of Formulation Examples 81 and 82, 410 mg tablets per tablet were prepared, and 10 tablets were taken per day. Based on the amount of Formulation Example 83, 410 mg tablets per tablet were prepared, and 12 tablets were taken per day. In Formulation Examples 72 to 74, licorice extract obtained from the crude drug in a yield of 15% was used. In Formulation Examples 79 to 83, in order to obtain 1 g of Shoseiryuto extract, Shoseiryuto extract using 750 mg of licorice in terms of crude drug was used.

(Formulation Example) Based on the amounts of Formulation Examples 84 to 85, wet granulation and then tableting were performed to prepare 165 mg tablets per tablet, and 2 tablets were taken per day. Based on the amounts of Formulation Examples 86 to 92, wet granulation and then tableting were performed to prepare 330 mg tablets per tablet, and 2 tablets were taken per day. In addition, 165 mg tablets per tablet were also prepared, and 4 tablets were taken per day. Based on the amounts of Formulation Examples 93 to 95, wet granulation and then tableting were performed to prepare 420 mg tablets per tablet, and 2 tablets were taken per day. In addition, 210 mg tablets per tablet were also prepared, and 4 tablets were taken per day.

Based on the amounts of Formulation Examples 96, 97, 99, and 103, 410 mg tablets per tablet were prepared, and 4 tablets were taken per day. Based on the amounts of Formulation Examples 100 and 104, 410 mg tablets per tablet were prepared, and 6 tablets were taken per day. Based on the amounts of Formulation Examples 98, 101, and 102, 410 mg tablets per tablet were prepared, and 8 tablets were taken per day. Based on the amounts of Formulation Examples 105 and 106, 410 mg tablets per tablet were prepared, and 10 tablets were taken per day. Based on the amount of Formulation Example 107, 410 mg tablets per tablet were prepared, and 12 tablets were taken per day. In Formulation Examples 96 to 97, licorice extract obtained from the crude drug in a yield of 15% was used. In Formulation Examples 103 to 107, in order to obtain 1 g of Shoseiryuto extract, Shoseiryuto extract using 750 mg of licorice in terms of crude drug was used.

Claims (12)

It contains fexofenadine hydrochloride, glycyrrhizinic acid and / or a salt thereof, and a water-soluble binder, and the amount of fexofenadine hydrochloride and / or a salt thereof is 0.15 to 1. A solid preparation for anti-allergy obtained by wet granulation in a proportion of 5 parts by mass. The solid preparation for anti-allergy according to claim 1, which contains 60 to 120 mg of fexofenadine hydrochloride as a daily dose. It contains olopatadine hydrochloride, glycyrrhizinic acid and / or a salt thereof, and a water-soluble binder, and the ratio of glycyrrhizic acid and / or a salt thereof is 2 to 15 parts by mass with respect to 1 part by mass of the olopatadine hydrochloride. A solid preparation for anti-allergy obtained by wet granulation. The solid preparation for anti-allergy according to claim 3, which contains 5 to 10 mg of olopatadine hydrochloride as a daily dose. The solid preparation for anti-allergy according to any one of claims 1 to 4, wherein the glycyrrhizic acid and / or a salt thereof is derived from licorice extract or licorice powder. The solid preparation for anti-allergy according to any one of claims 1 to 5, which contains 2 to 220 mg of glycyrrhizic acid and / or a salt thereof as a daily dose. The anti-antibody according to any one of claims 1 to 6, wherein the water-soluble binder is hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, potato starch, corn starch, pregelatinized starch, polyvinylpyrrolidone, or polyvinyl alcohol. Solid preparation for allergies. The solid preparation for anti-allergy according to any one of claims 1 to 7, wherein 0.03 to 2 parts by mass of the water-soluble binder is contained in 1 part by mass of the fexofenadine hydrochloride or olopatadine hydrochloride. .. A method for improving the granulation property of fexofenadine hydrochloride in wet granulation by coexisting fexofenadine hydrochloride, glycyrrhizinic acid and / or a salt thereof, and a water-soluble binder, wherein the fexofenadine hydrochloride is used. A method in which the ratio of glycyrrhizic acid and / or a salt thereof is 0.15 to 1.5 parts by mass with respect to 1 part by mass of hydrochloride. A method for improving the granulation property of olopatadine hydrochloride in wet granulation by coexisting olopatadine hydrochloride, glycyrrhizinic acid and / or a salt thereof, and a water-soluble binder, wherein 1 part by mass of the olopatadine hydrochloride is used. A method in which the glycyrrhizinic acid and / or a salt thereof is in a proportion of 2 to 15 parts by mass. A method for producing a solid preparation, which comprises blending fexofenadine hydrochloride, glycyrrhizinic acid and / or a salt thereof, and a water-soluble binder and performing wet granulation, wherein 1 part by mass of the fexofenadine hydrochloride. The method, wherein the glycyrrhizinic acid and / or a salt thereof is in a proportion of 0.15 to 1.5 parts by mass. A method for producing a solid preparation, which comprises blending olopatadine hydrochloride, glycyrrhizinic acid and / or a salt thereof, and a water-soluble binder and performing wet granulation. A method in which glycyrrhizic acid and / or a salt thereof is in a proportion of 2 to 15 parts by mass.

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