JP7629895B2 - Oral Compositions - Google Patents

Description

The present invention relates to an oral composition.

The function of the stomach and intestines is regulated by balancing the sympathetic and parasympathetic autonomic nervous systems. The stomach and intestines are affected by various external factors such as stress and diet, and if the balance of the autonomic nervous system is disrupted, the stomach and intestinal muscles may contract excessively, causing pain, or excess stomach acid may cause inflammation of the gastric mucosa, resulting in stomach pain. Stomach pain can also be caused by indigestion and loss of appetite.

For such gastrointestinal pain, various gastrointestinal medicines, including herbal medicines, are used depending on the symptoms and cause. Among herbal medicines, some gastrointestinal herbal medicines promote metabolism by stimulating gastrointestinal motility, while others relieve pain through their anti-inflammatory and analgesic effects (Patent Document 1). Other gastrointestinal medicines are also effective in protecting the gastric mucosa.

Capsules, a type of pharmaceutical product or health food, are highly portable and popular with users. Soft capsules have a smooth surface and are easy to swallow, making them popular with users. Common methods for manufacturing soft capsules include the flat plate method, rotary method, and seamless method.

In the rotary method (punching method), a sheet-like capsule shell sandwiches the flowing filling contents and forms a capsule shape along the holes of a rotating cylindrical die. On the other hand, in the seamless method (dropping method), the capsule shell composition and contents are simultaneously ejected from multiple concentric nozzles to form a seamless capsule shape.

Japanese Patent Application Publication No. 8-99890

Regardless of the manufacturing method, capsules, especially soft capsules, may experience uneven filling, foaming, and leakage if the liquids do not mix well when the contents are enclosed in the capsule shell. This can lead to reduced manufacturing efficiency and loss of uniformity in the effects and quality of the pharmaceutical product.

Therefore, the present invention aims to provide an oral composition that has good liquid compatibility between the capsule shell and the filling contents, is efficient to manufacture, and has consistent quality.

The present inventors have found a new problem that a composition containing (A) a gastrointestinal herbal medicine and/or a gastrointestinal anti-inflammatory and repairing component (hereinafter also referred to as (A) component in this specification) and (C) a hydrophobic base (hereinafter also referred to as (C) component in this specification) increases the dynamic contact angle with the capsule shell, resulting in poor liquid compatibility. The present inventors have also found that when (B) a nonionic surfactant (hereinafter also referred to as (B) component in this specification) and (C) a hydrophobic base coexist, the dynamic contact angle increases, and this combination also results in poor liquid compatibility. Focusing on these problems, the present inventors have conducted extensive research and found that the coexistence of the above (A), (B), and (C) components effectively improves liquid compatibility, leading to the completion of the present invention.

That is, the present invention provides an oral composition comprising: [1] (A) a gastrointestinal herbal medicine and/or a gastrointestinal anti-inflammatory repair component; (B) a nonionic surfactant; and (C) a hydrophobic base; [2] the oral composition according to [1], in which the gastrointestinal herbal medicine is at least one selected from the group consisting of magnolia bark, sophora rhizome, tangerine peel, fennel, cinnamon bark, turmeric, rhubarb, phellodendron bark, coptis rhizome, onji, gennoshoko, juglans japonica, swertia japonica, coix seed, and belladonna; [3] the oral composition according to [1], in which the gastrointestinal anti-inflammatory repair component is at least one selected from the group consisting of teprenone, rebamipide, aldioxa, azulene sulfonic acid, loxoprofen, trimebutine, pirenzepine, sucralfate, and salts thereof; and [4] The oral composition according to any one of [1] to [3], in which the hydrophobic base (C) is fats and/or waxes; [5] the oral composition according to any one of [1] to [4], which is a liquid oral composition; [6] a capsule in which the oral composition according to any one of [1] to [5] is filled in a capsule shell; [7] the oral composition according to [1] to [6], which is fast-dissolving and/or fast-releasing; [8] a method for imparting to the oral composition an effect of improving liquid compatibility with the capsule shell, comprising causing (A) a gastrointestinal herbal medicine and/or a gastrointestinal anti-inflammatory repair component, (B) a nonionic surfactant, and (C) a hydrophobic base to coexist in the oral composition; and the like.

In another embodiment, the present invention can also provide a method for producing a solid preparation, characterized in that (A) a gastrointestinal herbal medicine and/or a gastrointestinal anti-inflammatory repair component, (B) a nonionic surfactant, and (C) a hydrophobic base are present together in an oral composition.

The oral composition of the present invention contains (A) a gastrointestinal herbal medicine and/or a gastrointestinal anti-inflammatory repair component, (B) a nonionic surfactant, and (C) a hydrophobic base, which effectively improves compatibility with the capsule shell. In addition, the oral composition of the present invention has excellent rapid dissolution and rapid release of the drug due to improved dispersibility in water caused by the coexistence of the above-mentioned (A), (B), and (C) components.

[Oral composition] The oral composition of the present invention contains (A) a gastrointestinal herbal medicine and/or a gastrointestinal anti-inflammatory repair component, (B) a nonionic surfactant, and (C) a hydrophobic base.

[Component (A)] In this specification, gastrointestinal herbal medicine refers to a herbal medicine that has the function of improving gastrointestinal disorders or promoting gastrointestinal health. There are no limitations on gastrointestinal herbal medicines, so long as they have such functions.

In this specification, gastrointestinal herbal medicines may be any part of a specific herbal medicine (whole plant, flower, inflorescence, flower bud, inflorescence, leaf, branch, branch and leaf, rhizome, root bark, root, fruit, pericarp, legume, seed, etc.) that is used as is, dried, crushed, crushed and squeezed, or extracted with an extraction solvent. Herbal medicines derived from bark include Mallotus japonicus, Phellodendron bark, Phellodendron bark, Cinnamon bark, Magnolia bark, and Condurango. Examples of medicinal herbs derived from roots (rhizomes, tubers, root bark, roots) include turmeric, Uymma Root, Corydalis Root, Astragalus Root, Scutellaria Root, Coptis Rhizome, Zedoary, Kankyo, Licorice, Platycodon Root, Sophora Root, Gentian, Red Ginseng, Magnolia Root, Colombo, Bupleurum Root, Dioscorea Root, Peony Root, Ginger Root, Citrus Rhizome, Senega, Atractylodes Root, Sophora Root, Rhubarb, Angelica Root, Carrot Root, White Root, Saussurea Root, Rhubarb, Scopolia Root, Onji, Belladonna (Belladonna Root), and Tianma. Herbal medicines derived from aboveground parts (whole plant, aboveground stems, leaves, branches, flowers) include Asarum, Aloe, Cuckoo, Geranium, Spiraea, Swertia japonica, Perilla japonica, Clove, Bitter melon, Poria columbine, Geranium herb, Swertia japonica, and Uva-ursi. Herbal medicines derived from fruits (fruit, pericarp, and pseudocarp) include Fennel, Pheasant's Ginger, Crataegus crenata, Zanthoxylum chinensis, Chinese pepper, Chinese ginger, Chinese chili pepper, Japanese spruce, Yakuchi, and Citrine. Herbal medicines derived from seeds include Cassia japonica, Cassia japonica, Cardamomum aralia, Myristica fragrans, Areca nut, Job's tears, and Cassia japonica. Gastrointestinal herbal medicines may be used alone or in appropriate combinations of multiple types.

In this specification, gastrointestinal herbal medicines may have an upper limit of ash content as stated in the Japanese Pharmacopoeia and the Japanese Pharmacopoeia Standards for Herbal Medicines of "5% or less", "5% or more but not more than 7%, "7% or more but not more than 9%, "more than 9%, or no mention". Herbal medicines with an ash content of "5% or less" include aloe, scutellaria, Corydalis chinensis, Astragalus membranaceus, Coptis chinensis, Platycodon grandiflorum, cinnamon bark, Cassia chinensis, Kobushi berry, Japanese hawthorn, Senega, Chinese hawthorn, Chinese chimpanzee, Bitter melon, Myrrhizae fragrans, Carrot, Pinellia arvensis, Areca nut, Poria cocos, Saussurea arvensis, Coix seed, Uva-ursi, Cassia chinensis, and Tenma. Examples of herbal medicines with a "higher than 5% and lower than 7%" include Acacia Root, Scutellaria Baicalensis, Scutellaria Baicalensis, Onji, Zedoary, Kankyo, Licorice, Pheasant's Root, Sophora Root, Gentian, Magnolia Root, Bupleurum Root, Japanese Peony, Spiraea Root, Cardamom Root, Swertia Root, Atractylodes Root, Clove, Angelica Root, Spruce, Atractylodes Root, Belladonna, Rhus Root, and Scopolia Root. Examples of herbal medicines with a "higher than 7% and lower than 9%" include Turmeric, Phellodendron Bark, Euonymus Root, Colombo, Shitei, Scutellaria Baicalensis, Ginger, Citrus Rhizome, Capsicum Root, and Ryokyou. Examples of herbal medicines with a "higher than 9%" include Mallotus Japonicus, Fennel, Cuckoo Root, Gennoshoko, Kondurango, Spiraea Root, Jelly Herb, Sophora Herb, Perilla Herb, Rhubarb, and Yakuchi.

From the viewpoint of significantly achieving the effects of the present invention, the gastrointestinal herbal medicine is preferably a stomach-strengthening herbal medicine or an anti-inflammatory and analgesic herbal medicine, and more preferably at least one selected from the group consisting of Magnolia Root, Atractylodes Root, Citrus Unshiu, Fennel, Cinnamon Bark, Turmeric, Rhubarb, Phellodendron Bark, Coptis Rhizome, Onji, Gennoshoko, Jyu Myrrhizae, Swertia japonica, Coix Seed, and Belladonna. Examples of herbal medicines for stomachic purposes include Kouboku (thick bark), Soujutsu (atractylostridium tsargassum), Chinpi (citrus peel), Fennel (fennel), Cinnamon (cinnamon bark), Turmeric (turmeric), Gennoshoko (gen no shoko), Swertia britannica (this medicine), and Job's tears (▲yoku▼coix seed). Examples of herbal medicines for anti-inflammatory and analgesic purposes include Rhubarb (rhubarb), Phellodendron bark (huangbai), Coptis japonica (canthaceae), Onji (canthus officinalis), Belladonna, and Juyaku (ten medicine).

Among gastrointestinal herbal medicines, magnolia is obtained from the dried bark and root bark of Magnoliaceae plants, including but not limited to magnolia arborescens, magnolia obovata, and magnolia tree, and contains ingredients such as magnolol.

Among gastrointestinal herbal medicines, soujutsu is obtained from the dried rhizomes of the Asteraceae plant, including but not limited to, β-eudesmol, hinesol, and other ingredients.

Among gastrointestinal herbal medicines, chinpi is obtained from the dried peel of the Unshu mandarin fruit of the Rutaceae family, and contains ingredients such as hesperidin, nobiletin, and naringin.

Among gastrointestinal herbal medicines, fennel is obtained from the dried fruit of the Foeniculum vulgare, which is a member of the Umbelliferae family, and contains ingredients such as fennel, anethole, and estagole.

Among gastrointestinal herbal medicines, cinnamon is obtained from the dried bark of Lauraceae plants, including but not limited to Cinnamon Bark, Cinnamon Bark, and Ceylon Cinnamon, and contains ingredients such as cinnamaldehyde, cinnamyl acetate, and coumarin.

Among gastrointestinal herbal medicines, turmeric is made from the dried tuberous roots of plants of the ginger family, including, but not limited to, turmeric and yellow turmeric, and contains ingredients such as curcumin, turmerone, zingiberene, and cineole.

Among gastrointestinal herbal medicines, rhubarb is obtained from the dried roots and rhizomes of the Polygonaceae family Rheum genus plant, and contains ingredients such as sennosides A to F, aloe-emodin, rhein, and chrysophanol.

Among gastrointestinal herbal medicines, Phellodendron bark is obtained from the dried bark of plants of the genus Phellodendron of the Rutaceae family, including, but not limited to, Phellodendron amplexicaule and Phellodendron chinensis, and contains ingredients such as berberine, palmatine, magnoflorine, phellodendrin, and yateolidine.

Among gastrointestinal herbal medicines, Coptis japonica is obtained from the dried rhizomes of plants in the Ranunculaceae family, Coptis japonica, Coptis chinensis, Coptis umbellata ...

Among gastrointestinal herbal medicines, onji is obtained from the dried roots or root bark of Polygalaceae plants, including, but not limited to, Polygala tenuifoline, onjisaponins (A to G), cinnamic acid, xanthone derivatives, prosapogenin, polygalitol, and other ingredients.

Among gastrointestinal herbal medicines, geranium herb is obtained from the dried above-ground parts of Geraniaceae plants such as, but not limited to, geranium herb, and contains ingredients such as geraniin, quercetin, kaempferithrin, tannin, kaempferol, gallic acid, succinic acid, protocatechuic acid, pyrogallol, ellagic acid, kaempferol monorhamnoside, brevifoline, corilagin undecaacetate, and nonamethylcorilagin.

Among gastrointestinal herbal medicines, Houttuynia cordata is obtained from the dried above-ground parts of plants of the Houttuynia family, including, but not limited to, Houttuynia cordata, and contains ingredients such as quercetin, quercitrin, isoquercitrin, decanoyl acetaldehyde, alpha-pinene, limonene, 2-undecanone, dodecyl aldehyde, potassium salts, flavonoid glycosides, benzamide derivatives, lauric aldehyde, methyl-n-nonyl ketone methyl lauryl sulfide, and myrcene.

Among gastrointestinal herbal medicines, Swertia japonica is obtained by drying the whole flowering plant of Gentianaceae plants such as Swertia japonica, but is not limited to this, and contains ingredients such as swertiamarin, sweroside, gentiopicroside, amarogentin, amaroswellin, swertianin, swertianolin, veridifolin, norswertianin, methylswertianin, swertianolin, oleanolic acid, swertsin, swertiajaponin, isovitexin, desmethylveridifolin, methylveridifolin, and homoorientin.

Among the gastrointestinal herbal medicines, coix seed is obtained from the dried seeds of grasses such as, but not limited to, Job's tears, with the seed coat removed, and contains ingredients such as koixinden A, koixinden B, koixenolide, palmitic acid, and benzoxazinone.

Among gastrointestinal herbal medicines, belladonna is obtained from the dried roots of nightshade plants such as, but not limited to, belladonna, and contains ingredients such as hyoscyamine, atropine, norhyoscyamine, and scopolamine.

When gastrointestinal herbal medicines are used as extracts, the extraction solvent may be water (including hot water), alcohols such as methanol, ethanol, isopropanol, ethylene glycol, and glycerin, esters such as ethyl acetate, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, saturated hydrocarbons such as pentane, hexane, cyclopentane, and cyclohexane, aromatic hydrocarbons such as toluene, halogenated hydrocarbons such as dichloromethane and chloroform, and organic solvents such as dimethylformamide and dimethyl sulfoxide (which may all contain water), or a mixture of one or two of these solvents. Of these solvents, water, ethanol, or a mixture of these is preferred from the viewpoint of safety.

The extract of gastrointestinal herbal medicine may be a crude extract extracted from the whole plant or from a necessary part of the plant, or may be a product obtained by further purification or concentration, or may be obtained by synthesis, or a commercially available product may be used. There are no particular limitations on the method for obtaining the extract of gastrointestinal herbal medicine, and conventional extraction methods, purification methods, concentration methods, synthesis methods, dry powder methods, etc. may be used. In addition, the extract of gastrointestinal herbal medicine may satisfy the items listed in the 17th revised edition of the Japanese Pharmacopoeia.

Extracts of gastrointestinal herbal medicines may be used in liquid form, but if necessary, they may be used in concentrated liquid, semi-solid, solid, or powder form by reducing or removing the liquid content through drying processes such as vacuum drying, freeze drying, and spray drying.

In this specification, the gastrointestinal anti-inflammatory repair component refers to a component that has the function of improving inflammation in the gastrointestinal mucosa, etc., and/or the function of repairing damage to the gastrointestinal mucosa, etc. The gastrointestinal anti-inflammatory repair component is not limited as long as it is a herbal medicine having such a function, but from the viewpoint of significantly achieving the effects of the present invention, a gastrointestinal mucosa protecting component, an anti-inflammatory analgesic component, or a stomach health component is preferable, and at least one selected from the group consisting of teprenone, rebamipide, aldioxa, sucralfate, methylmethionine sulfonium chloride, sofalcone, cetraxate, troxipide, azulene sulfonic acid, loxoprofen, L-glutamine, berberine tannate, trimebutine, pirenzepine, and salts thereof is preferable. As the gastrointestinal mucosa protecting component, teprenone, rebamipide, aldioxa, sucralfate, etc., or their salts are more preferable, as the anti-inflammatory analgesic component, azulene sulfonic acid, loxoprofen, etc., or their salts are more preferable, and as the stomach health component, pirenzepine, trimebutine, etc., or their salts are more preferable.

Among the gastrointestinal anti-inflammatory repair ingredients, teprenone, rebamipide, aldioxa, sucralfate, methylmethionine sulfonium chloride, sofalcone, cetraxate, troxipide, azulene sulfonic acid, loxoprofen, L-glutamine, berberine tannate, trimebutine, or salts of pirenzepine are not particularly limited as long as they are medicamentarily, pharmacologically, or physiologically acceptable salts. Among at least one selected from the group consisting of teprenone, rebamipide, aldioxa, sucralfate, methylmethionine sulfonium chloride, sofalcone, cetraxate, troxipide, azulene sulfonic acid, loxoprofen, L-glutamine, berberine tannate, trimebutine, pirenzepine, and salts thereof, compounds that have optical isomers may be either the R-form or the S-form, and optically separated or racemic forms may be used.

In the present specification, examples of medicamentously, pharmacologically, or physiologically acceptable salts include organic acid salts, inorganic acid salts, salts with organic bases, and salts with inorganic bases. Examples of organic acid salts include monocarboxylates such as acetates, trifluoroacetates, butyrates, palmitates, and stearates; polycarboxylates such as fumarates, maleates, succinates, and malonates; oxycarboxylates such as lactates, tartrates, and citrates; and organic sulfonates such as methanesulfonates, toluenesulfonates, and tosylates. Examples of inorganic acid salts include hydrochlorides, sulfates, nitrates, hydrobromides, and phosphates. Examples of salts with organic bases include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, and ethylenediamine. Examples of salts with inorganic bases include ammonium salts; salts with alkali metals such as sodium or potassium, alkaline earth metals such as calcium or magnesium, and metals such as aluminum. These salts of teprenone, rebamipide, aldioxa, azulene sulfonic acid, loxoprofen, trimebutine, pirenzepine, or sucralfate may be used alone or in any combination of two or more. These salts may include solvates or hydrates of the salts. Although not limited, preferred medicamentarily, pharmacologically, or physiologically acceptable salts of azulene sulfonic acid or loxoprofen are sodium salts, known as azulene sulfonate sodium and loxoprofen sodium. Although not limited, preferred medicamentarily, pharmacologically, or physiologically acceptable salts of trimebutine are maleates, known as trimebutine maleates. Although not limited thereto, a preferred medicamentously, pharmacologically or physiologically acceptable salt of pirenzepine is the hydrochloride salt, known as pirenzepine hydrochloride. Although not limited thereto, a preferred medicamentously, pharmacologically or physiologically acceptable salt of sucralfate is sucrose sulfate aluminum salt.

The dose (administration amount) of component (A) in the oral composition of the present invention can be appropriately set depending on the types and amounts of components (B) and (C), the types and amounts of other components, the condition of the user (body weight, age, sex, symptoms, physical condition, etc.), and the dosage form of the oral composition of the present invention, and is not limited thereto. From the viewpoint of more significantly exerting the effects of the present invention, the daily oral administration amount of Magnolia Bark, expressed in terms of the amount of raw herbal medicine, can usually be about 0.1 to about 5000 mg, more preferably about 1 to about 4000 mg, even more preferably about 5 to about 3000 mg, particularly preferably about 10 to about 2500 mg, and most preferably about 20 to about 2000 mg. The daily oral dose of Magnolia bark extract, expressed in terms of the amount of raw herbal medicine, can be 10 to 8000 mg, more preferably 30 to 7000 mg, even more preferably 50 to 6000 mg, particularly preferably 80 to 5500 mg, and most preferably 100 to 5000 mg. The daily oral dose of Atractylodes rhizome, expressed in terms of the amount of raw herbal medicine, can be about 0.1 to about 5000 mg, more preferably about 1 to about 4000 mg, even more preferably about 5 to about 3000 mg, particularly preferably about 10 to about 2500 mg, and most preferably about 20 to about 2000 mg. The daily oral dose of Atractylodes rhizome extract, expressed in terms of the amount of raw herbal medicine, can be 10 to 8000 mg, more preferably 30 to 7000 mg, even more preferably 50 to 6000 mg, particularly preferably 80 to 5500 mg, and most preferably 100 to 5000 mg. The daily oral dose of Chinpi, expressed in terms of the amount of raw herbal medicine, can be about 0.1 to about 5000 mg, more preferably about 1 to about 4000 mg, even more preferably about 5 to about 3000 mg, particularly preferably about 10 to about 2500 mg, and most preferably about 20 to about 2000 mg. The daily oral dose of the chinpi extract, expressed in terms of the amount of the raw herb, can be 10 to 7000 mg, more preferably 30 to 6000 mg, even more preferably 50 to 5000 mg, particularly preferably 80 to 4500 mg, and most preferably 100 to 4000 mg. The daily oral dose of cinnamon, expressed in terms of the amount of the raw herb, can be about 0.1 to about 5000 mg, more preferably about 1 to about 4000 mg, even more preferably about 5 to about 3000 mg, particularly preferably about 10 to about 2500 mg, and most preferably about 20 to about 2000 mg. The daily oral dose of cinnamon extract, expressed in terms of the amount of raw herbal medicine, can be 10 to 8000 mg, more preferably 30 to 7000 mg, even more preferably 50 to 6000 mg, particularly preferably 80 to 5500 mg, and most preferably 100 to 5000 mg. The daily oral dose of turmeric, expressed in terms of the amount of raw herbal medicine, can be about 40 to about 4000 mg, more preferably about 80 to about 3000 mg, even more preferably about 180 to about 2500 mg, particularly preferably about 250 to about 1800 mg, and most preferably about 300 to about 1500 mg. The daily oral dose of turmeric extract, expressed in terms of the amount of raw herbal medicine, can be 200 to 8000 mg, more preferably 400 to 7000 mg, even more preferably 600 to 6000 mg, particularly preferably 700 to 5500 mg, and most preferably 800 to 5000 mg. The daily oral dose of Phellodendron Bark, expressed in terms of the amount of raw herbal medicine, can be about 0.1 to about 5000 mg, more preferably about 1 to about 4000 mg, even more preferably about 5 to about 3000 mg, particularly preferably about 10 to about 2500 mg, and most preferably about 20 to about 2000 mg. The daily oral dose of Phellodendron Bark extract, expressed in terms of the amount of raw herbal medicine, can be 10 to 7000 mg, more preferably 30 to 6000 mg, even more preferably 50 to 5000 mg, particularly preferably 80 to 4500 mg, and most preferably 100 to 4000 mg. The daily oral dose of Coptis Rhizome, expressed in terms of the amount of raw herbal medicine, can be about 0.1 to about 5000 mg, more preferably about 1 to about 4000 mg, even more preferably about 5 to about 3000 mg, particularly preferably about 10 to about 2500 mg, and most preferably about 20 to about 2000 mg. The daily oral dose of Coptis japonica extract, expressed in terms of the amount of crude drug, can be about 0.1 to about 5000 mg, more preferably about 1 to about 4000 mg, even more preferably about 5 to about 3000 mg, particularly preferably about 10 to about 2500 mg, and most preferably about 20 to about 2000 mg. The daily oral dose of Fennel, expressed in terms of the amount of crude drug, can be about 0.1 to about 5000 mg, more preferably about 1 to about 4000 mg, even more preferably about 5 to about 2500 mg, particularly preferably about 10 to about 1200 mg, and most preferably about 20 to about 800 mg. The daily oral dose of the fennel extract, expressed in terms of the amount of the original herbal medicine, can be 50 to 5000 mg, more preferably 150 to 4000 mg, even more preferably 300 to 3000 mg, particularly preferably 350 to 2500 mg, and most preferably 400 to 2000 mg. The daily oral dose of the rhubarb, expressed in terms of the amount of the original herbal medicine, can be about 0.01 to about 6500 mg, more preferably about 0.05 to about 1000 mg, even more preferably about 0.1 to about 500 mg, particularly preferably about 0.3 to about 300 mg, and most preferably about 0.5 to about 120 mg. The daily oral dose of the rhubarb extract, expressed in terms of the amount of the original herbal medicine, can be about 0.01 to about 500 mg, more preferably about 0.05 to about 400 mg, even more preferably about 0.1 to about 300 mg, particularly preferably about 0.3 to about 250 mg, and most preferably about 0.5 to about 200 mg. The daily oral dose of onji, expressed in terms of the amount of the original herbal medicine, can be about 100 to about 10,000 mg, more preferably about 150 to about 7,500 mg, even more preferably about 200 to about 5,000 mg, particularly preferably about 250 to about 3,000 mg, and most preferably about 300 to about 1,500 mg. The daily oral dose of the Onji extract, expressed in terms of the amount of the original herbal medicine, can be about 500 to about 5000 mg, more preferably about 650 to about 4500 mg, even more preferably about 800 to about 4000 mg, particularly preferably about 1000 to about 3000 mg, and most preferably about 1200 to about 2500 mg. The daily oral dose of Geranium Herb, expressed in terms of the amount of the original herbal medicine, can be about 10 to about 10000 mg, more preferably about 30 to about 7500 mg, even more preferably about 50 to about 5000 mg, particularly preferably about 80 to about 3000 mg, and most preferably about 100 to about 1000 mg. The daily oral dose of the Geranium Herb extract, expressed in terms of the amount of the original herbal medicine, can be about 100 to about 30,000 mg, more preferably about 400 to about 15,000 mg, even more preferably about 800 to about 10,000 mg, particularly preferably about 1,000 to about 8,000 mg, and most preferably about 1,500 to about 6,000 mg. The daily oral dose of the Herb Japonicus, expressed in terms of the amount of the original herbal medicine, can be about 20 to about 20,000 mg, more preferably about 30 to about 15,000 mg, even more preferably about 40 to about 8,000 mg, particularly preferably about 50 to about 5,000 mg, and most preferably about 70 to about 4,000 mg. The daily oral dose of the extract of Judas Herb, expressed in terms of the amount of the original herbal medicine, can be about 100 to about 25,000 mg, more preferably about 200 to about 20,000 mg, even more preferably about 400 to about 15,000 mg, particularly preferably about 800 to about 8,000 mg, and most preferably about 1,000 to about 5,000 mg. The daily oral dose of Swertia japonica, expressed in terms of the amount of the original herbal medicine, can be about 0.1 to about 1,500 mg, more preferably about 1 to about 700 mg, even more preferably about 3 to about 100 mg, particularly preferably about 5 to about 50 mg, and most preferably about 8 to about 20 mg. The daily oral dose of Swertia japonica extract, expressed in terms of the amount of raw herbal medicine, can be about 50 to about 3000 mg, more preferably about 100 to about 2000 mg, even more preferably about 120 to about 1500 mg, particularly preferably about 150 to about 1200 mg, and most preferably about 180 to about 1000 mg. The daily oral dose of Coix seed, expressed in terms of the amount of raw herbal medicine, can be about 200 to about 8000 mg, more preferably about 300 to about 7000 mg, even more preferably about 400 to about 5000 mg, particularly preferably about 500 to about 4000 mg, and most preferably about 600 to about 2500 mg. The daily oral dose of the coix seed extract, expressed in terms of the amount of the original herbal medicine, can be about 100 to about 30,000 mg, more preferably about 400 to about 20,000 mg, even more preferably about 800 to about 10,000 mg, particularly preferably about 1,000 to about 6,000 mg, and most preferably about 1,500 to about 3,000 mg. The daily oral dose of belladonna, expressed in terms of the amount of the original herbal medicine, can be about 1 to about 70 mg, more preferably about 1.5 to about 60 mg, even more preferably about 2 to about 40 mg, particularly preferably about 2.5 to about 20 mg, and most preferably about 3 to about 10 mg. The daily oral dose of the belladonna extract, expressed in terms of the amount of raw herbal medicine, can be about 1 to about 90 mg, more preferably about 2 to about 70 mg, even more preferably about 3 to about 40 mg, particularly preferably about 4 to about 20 mg, and most preferably about 5 to about 10 mg. In this specification, the term "rough herbal medicine equivalent" means the weight (dry weight) of the raw herbal medicine (herbal medicine mixture) required to obtain the amount of the ingredient. When an extract is used as a herbal medicine, the dry weight of the raw herbal medicine required to obtain the amount of the extract is the raw herbal medicine equivalent. The daily dose (dosage) may be taken in 1 to 3 divided doses.

The daily oral dose of teprenone can be 10 to 250 mg, more preferably 30 to 230 mg, even more preferably 50 to 200 mg, particularly preferably 80 to 180 mg, and most preferably 100 to 150 mg. The daily oral dose of rebamipide can be 10 to 380 mg, more preferably 20 to 370 mg, even more preferably 30 to 360 mg, particularly preferably 50 to 350 mg, and most preferably 100 to 300 mg. The daily oral dose of aldioxa can be 10 to 380 mg, more preferably 20 to 360 mg, even more preferably 30 to 340 mg, particularly preferably 50 to 320 mg, and most preferably 60 to 300 mg. The daily oral dose of sodium azulene sulfonate can be 0.05 to 100 mg, more preferably 0.1 to 60 mg, even more preferably 0.3 to 20 mg, particularly preferably 0.5 to 10 mg, and most preferably 1 to 6 mg. The daily oral dose of sodium loxoprofen can be 10 to 380 mg, more preferably 20 to 360 mg, even more preferably 30 to 340 mg, particularly preferably 50 to 320 mg, and most preferably 60 to 300 mg. The daily oral dose of trimebutine maleate can be 30 to 600 mg, more preferably 50 to 500 mg, even more preferably 80 to 400 mg, particularly preferably 100 to 300 mg, and most preferably 110 to 250 mg. The daily oral dose of pirenzepine hydrochloride can be 5 to 400 mg, more preferably 10 to 300 mg, even more preferably 15 to 200 mg, particularly preferably 26 to 150 mg, and most preferably 45 to 100 mg. The daily oral dose of sucralfate can be 200 to 2700 mg, more preferably 300 to 2000 mg, even more preferably 400 to 1500 mg, particularly preferably 500 to 900 mg, and most preferably 600 to 750 mg. The daily dose (dosage) may be taken in 1 to 3 divided doses.

The oral dose of Magnolia bark per dose, expressed in terms of the amount of raw herbal medicine, can be about 0.1 to about 1500 mg, more preferably about 1 to about 1000 mg, even more preferably about 5 to about 750 mg, particularly preferably about 8 to about 500 mg, and most preferably about 10 to about 50 mg. The oral dose of Magnolia bark extract per dose, expressed in terms of the amount of raw herbal medicine, can be 10 to 5000 mg, more preferably 25 to 3000 mg, even more preferably 50 to 2500 mg, particularly preferably 100 to 2000 mg, and most preferably 160 to 1700 mg. The oral dose of Atractylodes rhizome per administration, expressed in terms of the amount of raw herbal medicine, can be about 10 to about 3000 mg, more preferably about 20 to about 2000 mg, even more preferably about 30 to about 1500 mg, particularly preferably about 50 to about 1000 mg, and most preferably about 70 to about 700 mg. The oral dose of Atractylodes rhizome per administration, expressed in terms of the amount of raw herbal medicine, can be about 10 to 5000 mg, more preferably 25 to 3000 mg, even more preferably 50 to 2500 mg, particularly preferably 100 to 2000 mg, and most preferably 160 to 1700 mg. The oral dose of Chinpi, expressed in terms of the amount of the original herbal medicine, can be about 5 to about 5000 mg, more preferably about 10 to about 4000 mg, even more preferably about 20 to about 3000 mg, particularly preferably about 50 to about 1500 mg, and most preferably about 100 to about 1000 mg. The oral dose of Chinpi extract, expressed in terms of the amount of the original herbal medicine, can be 10 to 5000 mg, more preferably 25 to 3000 mg, even more preferably 50 to 2500 mg, particularly preferably 100 to 2000 mg, and most preferably 160 to 1700 mg. The oral dose of cinnamon per dose, expressed in terms of the amount of raw herbal medicine, can be about 0.5 to about 1500 mg, more preferably about 1 to about 1000 mg, even more preferably about 10 to about 800 mg, particularly preferably about 20 to about 500 mg, and most preferably about 30 to about 300 mg. The oral dose of cinnamon extract per dose, expressed in terms of the amount of raw herbal medicine, can be 10 to 5000 mg, more preferably 25 to 3000 mg, even more preferably 50 to 2500 mg, particularly preferably 100 to 2000 mg, and most preferably 160 to 1700 mg. The oral dose of turmeric, expressed in terms of the amount of raw herbal medicine, can be about 10 to about 3000 mg, more preferably about 20 to about 2000 mg, even more preferably about 30 to about 1500 mg, particularly preferably about 50 to about 1000 mg, and most preferably about 70 to about 700 mg. The oral dose of turmeric extract, expressed in terms of the amount of raw herbal medicine, can be 10 to 7000 mg, more preferably 50 to 6000 mg, even more preferably 100 to 4000 mg, particularly preferably 150 to 3000 mg, and most preferably 200 to 2000 mg. The oral dose of Phellodendron Bark per dose, expressed in terms of the amount of raw herbal medicine, can be about 5 to about 5000 mg, more preferably about 10 to about 4000 mg, even more preferably about 20 to about 3000 mg, particularly preferably about 50 to about 1500 mg, and most preferably about 100 to about 1000 mg. The oral dose of Phellodendron Bark extract per dose, expressed in terms of the amount of raw herbal medicine, can be 10 to 3000 mg, more preferably 30 to 2500 mg, even more preferably 50 to 2000 mg, particularly preferably 80 to 1500 mg, and most preferably 100 to 1000 mg. The oral dose of Coptis japonica per administration, expressed in terms of the amount of the original herbal medicine, can be about 0.1 to about 1500 mg, more preferably about 1 to about 1000 mg, even more preferably about 5 to about 750 mg, particularly preferably about 8 to about 500 mg, and most preferably about 10 to about 50 mg. The oral dose of Coptis japonica per administration, expressed in terms of the amount of the original herbal medicine, can be about 10 to about 3000 mg, more preferably about 30 to about 2500 mg, even more preferably about 50 to about 2000 mg, particularly preferably about 80 to about 1500 mg, and most preferably about 100 to about 1000 mg. The oral dose of fennel per administration, expressed in terms of the amount of the crude drug, can be about 0.1 to about 1000 mg, more preferably about 1 to about 850 mg, even more preferably about 5 to about 700 mg, particularly preferably about 20 to about 500 mg, and most preferably about 35 to about 350 mg. The oral dose of fennel extract per administration, expressed in terms of the amount of the crude drug, can be 10 to 3000 mg, more preferably 30 to 2500 mg, even more preferably 50 to 2000 mg, particularly preferably 80 to 1500 mg, and most preferably 100 to 1000 mg. The oral dose of Rhubarb, expressed in terms of the amount of the crude drug, can be about 0.01 to about 2000 mg, more preferably about 0.03 to about 1500 mg, even more preferably about 0.3 to about 1000 mg, particularly preferably about 3 to about 500 mg, and most preferably about 30 to about 100 mg. The oral dose of Rhubarb extract, expressed in terms of the amount of the crude drug, can be about 1 to about 300 mg, more preferably about 2 to about 250 mg, even more preferably about 4 to about 200 mg, particularly preferably about 6 to about 150 mg, and most preferably about 8 to about 100 mg. The oral dose of onji per dose, expressed in terms of the amount of the original herbal medicine, can be about 20 to about 7000 mg, more preferably about 40 to about 5000 mg, even more preferably about 60 to about 3000 mg, particularly preferably about 80 to about 1500 mg, and most preferably about 100 to about 1000 mg. The oral dose of onji extract per dose, expressed in terms of the amount of the original herbal medicine, can be about 20 to about 5000 mg, more preferably about 40 to about 4000 mg, even more preferably about 60 to about 3000 mg, particularly preferably about 80 to about 2000 mg, and most preferably about 100 to about 1000 mg. The oral dose of Geranium Herb, expressed in terms of the amount of the original herbal medicine, can be about 10 to about 3000 mg, more preferably about 30 to about 2000 mg, even more preferably about 50 to about 1500 mg, particularly preferably about 80 to about 1000 mg, and most preferably about 100 to about 800 mg. The oral dose of Geranium Herb, expressed in terms of the amount of the original herbal medicine, can be about 100 to about 7000 mg, more preferably about 150 to about 6000 mg, even more preferably about 200 to about 5000 mg, particularly preferably about 250 to about 4000 mg, and most preferably about 300 to about 3500 mg. The oral dose of Judas Herb, expressed in terms of the amount of raw herbal medicine, can be about 4 to about 7000 mg, more preferably about 8 to about 6000 mg, even more preferably about 12 to about 5000 mg, particularly preferably about 16 to about 3500 mg, and most preferably about 20 to about 2000 mg. The oral dose of Judas Herb extract, expressed in terms of the amount of raw herbal medicine, can be about 100 to about 11000 mg, more preferably about 200 to about 10000 mg, even more preferably about 300 to about 9000 mg, particularly preferably about 400 to about 7500 mg, and most preferably about 500 to about 5000 mg. The oral dose of Swertia japonica per administration, expressed in terms of the amount of the original herbal medicine, can be about 0.1 to about 300 mg, more preferably about 0.2 to about 200 mg, even more preferably about 0.3 to about 100 mg, particularly preferably about 0.4 to about 40 mg, and most preferably about 0.5 to about 20 mg. The oral dose of Swertia japonica extract per administration, expressed in terms of the amount of the original herbal medicine, can be about 10 to about 1000 mg, more preferably about 20 to about 800 mg, even more preferably about 30 to about 500 mg, particularly preferably about 40 to about 200 mg, and most preferably about 50 to about 100 mg. The oral dose of coix seed per dose, expressed in terms of the amount of the original herbal medicine, can be about 10 to about 6000 mg, more preferably about 30 to about 4500 mg, even more preferably about 50 to about 3000 mg, particularly preferably about 100 to about 1000 mg, and most preferably about 200 to about 7000 mg. The oral dose of coix seed per dose, expressed in terms of the amount of the original herbal medicine, can be about 100 to about 20000 mg, more preferably about 200 to about 11000 mg, even more preferably about 300 to about 9500 mg, particularly preferably about 500 to about 8000 mg, and most preferably about 700 to about 6500 mg. The oral dose of belladonna per administration, expressed in terms of the amount of the original herbal medicine, can be about 1 to about 50 mg, more preferably about 1.5 to about 40 mg, even more preferably about 2 to about 30 mg, particularly preferably about 2.5 to about 20 mg, and most preferably about 3 to about 10 mg. The oral dose of belladonna extract per administration, expressed in terms of the amount of the original herbal medicine, can be about 0.1 to about 40 mg, more preferably about 1 to about 30 mg, even more preferably about 2 to about 20 mg, particularly preferably about 3 to about 15 mg, and most preferably about 4 to about 10 mg. The dosage per administration (dosage) can be divided into 1 to 3 capsules depending on the dosage form, for example, in the case of capsules, it can be taken in portions.

The oral dose of teprenone can be 15 to 150 mg, more preferably 20 to 120 mg, even more preferably 25 to 90 mg, particularly preferably 30 to 75 mg, and most preferably 35 to 50 mg. The oral dose of rebamipide can be 1 to 300 mg, more preferably 5 to 200 mg, even more preferably 10 to 150 mg, particularly preferably 20 to 100 mg, and most preferably 30 to 50 mg. The oral dose of aldioxa can be 1 to 300 mg, more preferably 5 to 250 mg, even more preferably 10 to 200 mg, particularly preferably 15 to 150 mg, and most preferably 20 to 100 mg. The oral dose of sodium azulene sulfonate per administration can be 0.05 to 30 mg, more preferably 0.1 to 20 mg, even more preferably 0.2 to 10 mg, particularly preferably 0.3 to 7 mg, and most preferably 0.4 to 2 mg. The oral dose of sodium loxoprofen per administration can be 5 to 300 mg, more preferably 10 to 250 mg, even more preferably 20 to 200 mg, particularly preferably 30 to 150 mg, and most preferably 40 to 120 mg. The oral dose of trimebutine maleate per administration can be 10 to 500 mg, more preferably 30 to 400 mg, even more preferably 50 to 300 mg, particularly preferably 80 to 200 mg, and most preferably 100 to 150 mg. The oral dose of pirenzepine hydrochloride can be 0.1 to 150 mg, more preferably 1 to 100 mg, even more preferably 5 to 70 mg, particularly preferably 10 to 45 mg, and most preferably 15 to 26 mg. The oral dose of sucralfate can be 30 to 2000 mg, more preferably 50 to 1500 mg, even more preferably 100 to 1200 mg, particularly preferably 150 to 900 mg, and most preferably 200 to 500 mg. The dosage (administration) per administration can be determined according to the dosage form, for example, in the case of capsules, it can be divided into 1 to 3 capsules.

The content of component (A) in the oral composition of the present invention can be appropriately set depending on the dosage form and the number of doses to be administered so as to achieve the above-mentioned dosage amount, and is not limited to, for example, based on the total amount of the oral composition, it can be 90% by mass or less (less), 80% by mass or less (less), 70% by mass or less (less), 60% by mass or less (less), 50% by mass or less (less), 45% by mass or less (less), 40% by mass or less (less), 30% by mass or less (less), 20% by mass or less (less), 15% by mass or less, 10% by mass or less, or 5% by mass or less. The content of the component (A) in the oral composition of the present invention is not limited, but may be, for example, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, or 0.5% by mass or more, based on the total amount of the oral composition. The content of the component (A) in the oral composition of the present invention is not limited, but may be, for example, 0.001 to 90% by mass, preferably 0.005 to 80% by mass, more preferably 0.01 to 70% by mass, even more preferably 0.05 to 60% by mass, and even more preferably 0.1 to 50% by mass, based on the total amount of the oral composition.

[Component (B)] The nonionic surfactant (B) in the oral composition of the present invention, when coexisting with the component (C) described below, causes a problem of reducing the liquid compatibility of the oral composition with the capsule shell. On the other hand, the component (B) is a component that can improve the liquid compatibility of the oral composition with the capsule shell when coexisting with the components (A) and (C).

Among the components (B) in the oral composition of the present invention, the nonionic surfactant is not particularly limited, as long as it is medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable.

In the present invention, any nonionic surfactant can be used as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable, for example, polyoxyethylene (hereinafter also referred to as POE)-polyoxypropylene (hereinafter also referred to as POP) block copolymers (e.g., poloxamers such as poloxamer 407, poloxamer 235, and poloxamer 188); POE-POP block copolymer adducts of ethylenediamine such as poloxamine; monolaurate; POE sorbitan fatty acid esters such as POE (20) sorbitan monooleate (polysorbate 20), POE (20) sorbitan monooleate (polysorbate 80), POE sorbitan monostearate (polysorbate 60), and POE sorbitan tristearate (polysorbate 65); propylene glycol fatty acid esters such as propylene glycol monostearate; POE (5) hydrogenated castor oil, POE (10) hydrogenated castor oil, and POE (20) hydrogenated castor oil. POE castor oils such as POE (40) hydrogenated castor oil, POE (50) hydrogenated castor oil, POE (60) hydrogenated castor oil, POE (100) hydrogenated castor oil, POE (3) castor oil, POE (10) castor oil, and POE (35) castor oil; POE alkyl ethers such as POE (9) lauryl ether; POE/POP alkyl ethers such as POE (20) POP (4) cetyl ether; POE alkyl ethers such as POE (10) nonylphenyl ether. alkylphenyl ether, polyethylene glycol monostearate such as polyoxyl 40 stearate, propylene glycol fatty acid esters such as propylene glycol monostearate, sucrose fatty acid esters, glycerin fatty acid esters such as glyceryl monostearate, sorbitan sesquioleate, sorbitan monostearate, sorbitan monooleate, sorbitan trioleate, and the like. The numbers in parentheses indicate the average number of moles of POP or POE added. Although not limited thereto, among these nonionic surfactants, from the viewpoint of more significantly exerting the effects of the present invention, at least one selected from the group consisting of POE castor oil, propylene glycol fatty acid ester, glycerin fatty acid ester, sucrose fatty acid ester, and sorbitan fatty acid ester is preferred, at least one selected from the group consisting of POE hydrogenated castor oil, propylene glycol monostearate, glyceryl monostearate, sucrose fatty acid ester, POE sorbitan fatty acid ester, and sorbitan fatty acid ester is more preferred, at least one selected from the group consisting of POE (60) hydrogenated castor oil, propylene glycol monostearate, glyceryl monostearate, sucrose stearate, polysorbate 80, and sorbitan sesquioleate is more preferred, and glycerin fatty acid ester, propylene glycol fatty acid ester, and/or polysorbate 80 are even more preferred. These nonionic surfactants may be synthesized by a known method and used, or may be commercially available products and used. The nonionic surfactants may be used alone or in combination of two or more kinds.

In the present invention, the HLB value of the nonionic surfactant is not particularly limited, but can be 7 or more from the viewpoint of more significantly exerting the effects of the present invention. Preferably, the HLB value is 10 to 20, more preferably 12 to 19.5, and even more preferably 13 to 18. In addition, the HLB value of the nonionic surfactant used in the present invention is not particularly limited, but can be less than 7 from a different viewpoint, and in this case, the HLB value is preferably 1.5 to 6.5, more preferably 2 to 6.5, and even more preferably 2.5 to 6. The HLB value is a value generally used in the field to evaluate the properties of nonionic surfactants, and is also called the hydrophilic-lipophilic balance. The HLB value is generally calculated as the ratio of the hydrophilic portion to the entire molecule, and a small HLB value tends to be highly lipophilic, while a high HLB value tends to be highly hydrophilic.

In the oral composition of the present invention, the content of component (B) can be appropriately set depending on the types and amounts of components (A) and (C), the types and amounts of other components, the patient's condition (body weight, age, sex, symptoms, physical condition, etc.), and the dosage form of the oral composition of the present invention, and is not limited thereto. From the viewpoint of more significantly exerting the effects of the present invention, the total amount of component (B) can be 0.1 to 80% by mass, preferably 1 to 60% by mass, more preferably 2 to 40% by mass, and particularly preferably 4 to 20% by mass, based on the total amount of the oral composition.

The blending ratio of component (A) to component (B) in the oral composition of the present invention can be appropriately set depending on the types of component (A) and component (B), the types and amounts of other components, and the dosage form of the oral composition of the present invention, but from the viewpoint of more significantly exerting the effects of the present invention, the total amount of component (B) per part by mass of component (A) can be 0.001 to 150 parts by mass, preferably 0.003 to 100 parts by mass, more preferably 0.005 to 60 parts by mass, even more preferably 0.008 to 20 parts by mass, and most preferably 0.01 to 10 parts by mass.

[Component (C)] The hydrophobic base (C) in the oral composition of the present invention, when coexisting with component (A), causes a problem of reducing the liquid compatibility of the oral composition with the capsule shell. In addition, when coexisting with component (B), the hydrophobic base (C) can also reduce the liquid compatibility of the oral composition with the capsule shell. On the other hand, component (C) is a component that can improve the liquid compatibility of the oral composition with the capsule shell by coexisting with components (A) and (B). In addition, when components (A), (B) and (C) coexist in the oral composition, the dispersibility in water can be improved. By exhibiting high dispersibility in water, the active ingredient is quickly dissolved (fast dissolution effect) and/or quickly released (fast release effect) from the oral composition in the body. Therefore, the drug absorbability in the body is improved, and it is possible to provide an oral composition that is highly effective against diseases, symptoms and conditions for which a therapeutic effect or health promotion effect is expected based on the pharmacological action of component (A).

The hydrophobic base is a hydrophobic base that disperses at least one of the components (A) and (B), and preferably all of the components (A) and (B). Here, "hydrophobic" specifically means that the water solubility of the "hydrophobic base" is 10 g/100 g or less, preferably 1 g/100 g or less, and more preferably 0.1 g/100 g or less. This solubility can be measured in accordance with the solubility test described in the General Rules of the Japanese Pharmacopoeia, 16th Edition.

The hydrophobic base in the present invention is not particularly limited, but any base that is liquid at 60°C (preferably 37°C, more preferably 20°C) is preferred as a hydrophobic base that is typically used in the filling solution for soft capsules.

In the present invention, any hydrophobic base can be used as long as it is medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable, such as fats and oils, waxes, and hydrocarbons.

In this specification, fats and oils refer to compounds in which fatty acids are ester-bonded to a glycerin skeleton, i.e., fats and oils whose main component is glyceride. Fat and oils include, but are not limited to, vegetable fats and oils such as castor oil, cottonseed oil, soybean oil, camellia oil, olive oil, sesame oil, peanut oil, corn oil, coconut oil, rapeseed oil, wheat germ oil, safflower oil, sunflower oil, safflower oil, perilla oil, hardened oil, and cacao butter; animal fats and oils such as lard, beef tallow, milk fat, and liver oil stabilized by hydrogenating coconut oil; mineral fats and oils such as silicone oil; and functional fats and oils such as medium-chain fatty acid triglycerides and long-chain fatty acid triglycerides. From the viewpoint of achieving the effects of the present invention, vegetable fats and oils preferably have an oleic acid content of 50% or more. From another viewpoint, vegetable fats and oils preferably have an oleic acid content of less than 50%.

Functional oils and fats include, but are not limited to, compounds in which short-chain fatty acids with 2 to 4 carbon atoms, medium-chain fatty acids with 5 to 12 carbon atoms, or fatty acids with a chain length of more than 12 carbon atoms are ester-bonded to mono- to decaglycerin. Short-chain fatty acids include butyric acid, etc., medium-chain fatty acids include valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, lauric acid, etc., and long-chain fatty acids include myristic acid, pentadecylic acid, palmitic acid, palmitoleic acid, margaric acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid, lignoceric acid, nervonic acid, cerotic acid, montanic acid, melissic acid, etc.

In this specification, wax refers to an ester of a higher fatty acid and a higher alcohol. Examples of waxes include, but are not limited to, beeswax, white beeswax, spermaceti, carnauba wax, lanolin, etc.

Hydrocarbons include, but are not limited to, squalene, squalane, yellow petrolatum, white petrolatum, heavy liquid paraffin, light liquid paraffin, semi-liquid paraffin, liquid isoparaffin, etc.

Among these (C) components, from the viewpoint of more significantly exerting the effect of improving the liquid compatibility of the oral composition with the capsule shell by coexisting with the (A) and (B) components, fats and/or oils are preferred, and as fats and oils, functional fats and/or vegetable fats are more preferred, fats and oils containing triglycerides are more preferred, and at least one selected from the group consisting of medium-chain fatty acid triglycerides, corn oil, soybean oil, safflower oil and olive oil is even more preferred, and medium-chain fatty acid triglycerides, soybean oil and/or safflower oil are particularly preferred. In this specification, medium-chain fatty acid triglycerides refer to glycerin triesters of fatty acids having 4 to 12 carbon atoms, and include mixtures consisting mostly of fatty acid triglycerides having these carbon numbers. Examples include, but are not limited to, fatty acid triglycerides mainly consisting of fatty acid triglycerides having 8 carbon atoms (caprylic acid) or 10 carbon atoms (capric acid). These can be obtained by hydrolyzing coconut oil, palm kernel oil, etc., refining it, and then compounding it again, or they can be synthetic products. From another perspective, component (C) is preferably a wax, and white beeswax is more preferable.

Specific examples of medium-chain triglyceride products (trade names) include Miglyol (manufactured by Mitsuba Trading Co., Ltd.), Coconard (registered trademark) (manufactured by Kao Corporation), ODO (manufactured by Nisshin Oillio Co., Ltd.), Panaceate (registered trademark) (manufactured by Nippon Oil & Fats Co., Ltd.), TCG-M (manufactured by Kokyu Alcohol Kogyo Co., Ltd.), Actor (manufactured by Riken Vitamin Co., Ltd.), and PALMESTER (manufactured by PALM-OLEO Co., Ltd.).

These (C) components may be synthesized by known methods or may be obtained commercially and used. (C) components may be used alone or in combination of two or more.

In the oral composition of the present invention, component (C) is preferably a clear liquid at 60°C.

In the present invention, the content of component (C) can be appropriately set depending on the types and amounts of components (A) and (B), the types and amounts of other components, the patient's condition (body weight, age, sex, symptoms, physical condition, etc.), and the dosage form of the oral composition of the present invention. The content of component (C) is not limited, but from the viewpoint of more significantly exerting the effects of the present invention, the total amount of component (C) can be 15 to 99% by mass, preferably 25 to 98% by mass, more preferably 30 to 97% by mass, even more preferably 40 to 96% by mass, and particularly preferably 50 to 95% by mass, based on the total amount of the oral composition.

The blending ratio of component (A) to component (C) in the oral composition of the present invention can be set appropriately depending on the type of component (A), the types and amounts of other components, the use of the oral composition, etc., but for example, the total amount of component (C) per part by mass of component (A) can be 0.01 to 300 parts by mass, preferably 0.01 to 200 parts by mass, more preferably 0.01 to 150 parts by mass, even more preferably 0.01 to 100 parts by mass, even more preferably 0.05 to 80 parts by mass, and particularly preferably 0.1 to 50 parts by mass.

The blending ratio of the (B) component and the (C) component in the oral composition of the present invention can be appropriately set depending on the type of the (B) component, the types and amounts of the other components, the use of the oral composition, etc., but from the viewpoint of more significantly exerting the effects of the present invention, the total amount of the (C) component can be 0.01 to 300 parts by mass, preferably 0.1 to 200 parts by mass, more preferably 0.5 to 150 parts by mass, and even more preferably 1 to 100 parts by mass per part by mass of the total amount of the (B) component.

[Biologically active ingredients] In the present invention, the oral composition may contain other ingredients (biologically active ingredients) as long as the effects of the present invention are sufficiently achieved.

Such ingredients include, for example, antihistamine ingredients (e.g., isothipendyl hydrochloride, iproheptine hydrochloride, difeterol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, triprolidine hydrochloride hydrate, tripelennamine hydrochloride, thonzylamine hydrochloride, promethazine hydrochloride, methdilazine hydrochloride, diphenhydramine salicylate, diphenyldisulfonate carbinoxamine, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline theoclate, carbinoxamine maleate, chlorpheniramine maleate, promethazine methylenedisalicylate), parasympathetic nerve blocking ingredients (e.g., atropine, scopolamine, belladonna total alkaloids, isopropamide iodide, Datura extract, Scopolia extract, etc.), Sympathomimetic components (e.g., methylephedrine, pseudoephedrine, phenylephrine, phenylpropanolamine, ephedrine, etilefrine, methoxamine, midodrine, methoxyphenamine, or salts thereof), anti-inflammatory enzymes (e.g., lysozyme, serrapeptase, bromelain, pronase, lipase AP6, etc.), herbal medicines and herbal medicine-derived components (e.g., ginger, licorice, ginseng, ephedra, kettle, saishin, nandina, oak, angelica, zenko, bellflower, schizophyllum, bezoar, zedoary, byadenioides, gentiana, ginseng, clove, senega, schizophyllum, schizophyllum, glycine ... Xanthine derivatives (e.g., caffeine such as sodium caffeine benzoate, caffeine hydrate, anhydrous caffeine, theophylline, aminophylline, theobromine, diprofeiline, proxyphylline, pentoxifylline, etc.), antipyretic analgesic ingredients (e.g., aspirin, aluminum aspirin, acetaminophen, ethenzamide, sazapirine, salicylamide, sodium salicylate, lactylphenetidine, ibuprofen, ketoprofen, tiaramide, aluminoprofen, etc.), leukotriene antagonist ingredients (montelukast, pranlukast, zafirlukast, etc.), antitussive ingredients (e.g., achloramide, cloperastine, pentoxyverine (carbetapentane), tipepidine, dibunate, dextromethorphan, codeine, dihydrocodeine, noscapine, etc.), expectorant (e.g., potassium guaiacolsulfonate, guaifenesin, etc.), Mucous membrane repair components (e.g., sodium copper chlorophyllin, etc.), vitamins (e.g., vitamin A [e.g., retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene, etc.], vitamin B [e.g., thiamine, thiamine disulfide, dicethiamine, octotiamine, shikotiamine, bis-ibuthiamine, bis-bentiamine, prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adenine dinucleotide, pyridoxine, pyridoxal, hydroxocobalamin, cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folic acid, tetrahydrofolic acid, dihydrofolic acid, nicotinic acid, nicotinamide , nicotinyl alcohol, pantothenic acid, panthenol, biotin, choline, inositol, etc.], vitamin C [for example, ascorbic acid, erythorbic acid, or derivatives thereof, etc.], vitamin D [for example, ergocalciferol, cholecalciferol, hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotachysterol, etc.], vitamin E [for example, tocopherol and its derivatives, ubiquinone derivatives, etc.], other vitamins [for example, hesperidin, carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin, eriocitrin, etc.], etc.], and Mucosal protective ingredients (for example, aluminum-based mucosal protective agents such as aminoacetic acid, dried aluminum hydroxide gel, and dihydroxyaluminum aminoacetate; magnesium-based mucosal protective agents such as magnesium aluminometasilicate, aluminum silicate, hydrotalcite, magnesium alumina hydroxide, aluminum hydroxide gel, co-precipitation product of aluminum hydroxide and sodium hydrogen carbonate, mixed dried gel of aluminum hydroxide and magnesium carbonate, co-precipitation product of aluminum hydroxide, calcium carbonate, and magnesium carbonate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium silicate, and co-precipitation product of magnesium hydroxide and aluminum potassium sulfate, sodium hydrogen carbonate, precipitated calcium carbonate, etc.), etc.

These components may be in the free form or as salts.

[Additives] In the present invention, the oral composition may contain additives that are commonly used in soft capsules, etc., as long as the effects of the present invention are sufficiently achieved.

As such additives, any component that can be normally used in medicines, quasi-drugs, and foods may be appropriately blended. The components that can be blended are not particularly limited, but examples include carrier components or additives, and examples of carrier components or additives in solid preparations include excipients, disintegrants, binders, lubricants, antioxidants, coating agents, colorants, flavoring agents, surfactants other than component (B), plasticizers, sweeteners, flavoring agents, disintegration aids, foaming agents, adsorbents, preservatives, wetting agents, and antistatic agents. Examples of carrier components or additives in liquid preparations include solvents, pH adjusters, refreshing agents, suspending agents, antifoaming agents, thickening agents, dissolution aids, the above-mentioned surfactants, antioxidants, colorants, sweeteners, and flavoring agents, as well as preservatives/antibacterial agents, chelating agents, solubilizers or dissolution aids, stabilizers, fluidizing agents, emulsifiers, thickeners, buffers, isotonicity agents, and dispersants. Specific examples of ingredients that can be optionally blended are given below, but are not limited to these ingredients. Although not limited, it is preferable to blend ingredients so as not to create a composition that reduces the fluidity of the oral composition, which would interfere with the effects of the present invention. For example, crospovidone (polyvinylpolypyrrolidone) is not preferable because blending it in an amount exceeding 5% reduces the fluidity of the oral composition. The oral composition of the present invention preferably contains less than 5% polyvinylpolypyrrolidone, and more preferably 4.5% or less.

Excipients: sugar alcohols such as D-sorbitol, mannitol, and xylitol; sugars such as glucose, sucrose, lactose, and fructose; crystalline cellulose, carmellose sodium, croscarmellose sodium, calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titanium oxide, magnesium aluminometasilicate, calcium silicate, talc, kaolin, etc. Excipients are preferably mannitol, croscarmellose sodium, and light anhydrous silicic acid, but are not particularly limited thereto.

Disintegrants: low-substituted hydroxypropyl cellulose, calcium carboxymethylcellulose, croscarmellose sodium, hydroxypropyl starch, partially pregelatinized starch, etc.

Binders: Cellulose derivatives such as methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic acid polymers, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol alginate, etc.

Lubricant: stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, dimethylpolysiloxane, etc.). As a lubricant, magnesium stearate is preferred, but is not particularly limited. When the oral composition of the present invention is used as a liquid oral composition, it is not preferred to contain 1% by mass or more, 2% by mass or more, 3% by mass or more, or 4% by mass or more of a stearate salt as a lubricant, from the viewpoint of fully achieving the effects of the present invention.

Antioxidants: dibutylhydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), tocopherol, citric acid, etc.

Coating agents: Hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethylcellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxymethyl ethylcellulose, cellulose acetate phthalate, polyvinyl acetal diethylamino acetate, aminoalkyl methacrylate copolymer, hydroxypropyl methylcellulose acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylamino acetate, shellac, etc.

Coloring agents: Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Red No. 106, Food Yellow No. 4, Food Yellow No. 5, Food Blue No. 1, Food Yellow No. 4 metal lake, riboflavin, carotene liquid, etc.

Flavoring agents: aspartame, ascorbic acid, stevia, menthol, crude licorice extract, simple syrup, etc.

Surfactants other than component (B): amphoteric surfactants, cationic surfactants, anionic surfactants, etc. Specific examples of amphoteric surfactants include lecithin such as soybean lecithin and egg yolk lecithin, alkyldiaminoethylglycine or its salts (e.g., hydrochloride, etc.). Specific examples of cationic surfactants include benzalkonium chloride and benzethonium chloride. Specific examples of anionic surfactants include alkylbenzenesulfonates, alkyl sulfates, polyoxyethylene alkyl sulfates, aliphatic α-sulfomethyl esters, α-olefin sulfonic acid, etc.

Plasticizers: triethyl citrate, polyethylene glycol, triacetin, cetanol, etc.

Sweeteners: Natural or synthetic sweeteners such as sucrose, mannitol, aspartame, etc.

Flavoring agents: menthol, camphor, borneol, cinnamaldehyde, lemon oil, etc.

Solvents: Water, ethanol, isopropanol, lauryl alcohol, cetearyl alcohol, stearyl alcohol, oleyl alcohol, lanolin alcohol, behenyl alcohol, 2-hexyldecanol, isostearyl alcohol, 2-octyldodecanol, etc.

pH adjusters: citric acid, malic acid, sodium hydrogen phosphate, dipotassium phosphate, etc.

Refreshing agents: l-menthol, peppermint water, etc.

Suspending agents: kaolin, sodium carmellose, xanthan gum, methylcellulose, tragacanth, etc.

Antifoaming agents: dimethylpolysiloxane, silicone antifoaming agents, etc.

Thickening agents: xanthan gum, tragacanth, methylcellulose, dextrin, etc.

Solubilizers: Ethanol, Macrogol (Macrogol 300, Macrogol 400, Macrogol 1500, Macrogol 4000, Macrogol 6000), etc.

In the present invention, the oral composition may or may not contain water, as long as the effects of the present invention are sufficiently achieved. In this specification, the water content refers to the total amount of water, including the water contained in the raw materials themselves, such as herbal medicines. The water content can be set appropriately depending on the type and amount of other ingredients, the use of the oral composition, etc., and can be, for example, 20% by mass or less (less) based on the total amount of the oral composition, preferably 15% by mass or less (less), more preferably 10% by mass or less (less), even more preferably 8% by mass or less (less), even more preferably 6% by mass or less (less), even more preferably 4% by mass or less (less), even more preferably 2% by mass or less (less), and even more preferably 1% by mass or less (less). The water content can be, for example, 0.00001% by mass or more, preferably 0.00005% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.0005% by mass or more, even more preferably 0.001% by mass or more, even more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, and even more preferably 0.05% by mass or more, based on the total amount of the oral composition.

In the present invention, the water used in the oral composition may be physiologically or pharma- ceutical acceptable. Examples of such water include distilled water, tap water, purified water, sterile purified water, water for injection, and distilled water for injection. These definitions are based on the 16th Edition of the Japanese Pharmacopoeia.

[Dosage form] The oral composition of the present invention can be prepared in various dosage forms as a solid preparation according to a method known to those skilled in the art. There is no particular limitation on the shape or size of the solid preparation, and examples of solid preparations for oral administration include tablets [including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets, film-coated tablets, plain tablets, sugar-coated tablets, etc.], capsules [including hard capsules and soft capsules, etc.], granules [including effervescent granules], powders, powders, fine granules, pills, oral tablets [including lozenges, sublingual tablets, buccal tablets, adhesive tablets, gums, etc.], films, dry syrups, jellies, oral semisolid preparations, confectionery preparations [including candies, gummies, nougat, etc.], and the like. Among these solid preparations, in order to more significantly exert the effects of the present invention, the oral composition of the present invention is preferably used in a capsule formulation, and more preferably in a soft capsule formulation, in order to make it easier to take because components with unpleasant tastes and odors are effectively masked in the mouth.

When the oral composition of the present invention is made into a capsule, it can be prepared by filling the oral composition of the present invention into a capsule shell, and the oral composition to be filled is preferably liquid. In this specification, liquid means having fluidity. Although not limited, such fluidity may be present in a temperature range that occurs in a known manufacturing method when filling into a capsule shell, etc., and fluidity may be lost after filling into the capsule shell, etc. Furthermore, although not limited, from the viewpoint of rapid dissolution and rapid release of a drug, it is sufficient that the composition has fluidity at body temperature. Although not limited, for example, a gel that does not flow continuously and uniformly when filled into a capsule shell, etc. is not preferable in terms of fluidity. In another embodiment, the oral composition of the present invention can be used for filling into a capsule shell. In this specification, the capsule shell refers to a membrane that has a space inside and can hold the contents such as an active ingredient while being confined inside. The liquid nature of the oral composition to be filled is not particularly limited, but is preferably aqueous or oily, and more preferably oily.

The capsule shell that can be used in the present invention is not particularly limited, but from the viewpoint of effectively achieving liquid compatibility of the oral composition with the capsule shell, a soft capsule shell is preferred. The base of the soft capsule shell is not particularly limited, but starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin, etc. can be used, with starch, gelatin, and succinated gelatin being preferred, and gelatin and succinated gelatin being more preferred. These may be used alone or in combination of two or more types.

When gelatin is contained in the capsule shell, the gelatin content is not particularly limited, but is preferably 20 to 99.5% by mass, more preferably 25 to 95% by mass, even more preferably 30 to 90% by mass, and particularly preferably 33 to 85% by mass, based on the total amount of the capsule shell.

The capsule shell may contain a plasticizer, a gelling agent, a gelling aid, a coloring agent, a preservative, a fragrance, a pH adjuster, a surfactant, etc., within a range that does not impair the effects of the present invention. As the plasticizer, glycerin, mannitol, sorbitol, sucrose, fructose, propylene glycol, macrogol, polyvinylpyrrolidone, etc. can be used. As the gelling agent, gum arabic, alginic acid, carrageenan, agar, xanthan gum, guar gum, glucomannan, gellan gum, tamarind gum, furcellaran, pectin, etc. can be used. As the gelling promoter, ammonium chloride, potassium chloride, calcium chloride, sodium chloride, potassium citrate, sodium citrate, magnesium sulfate, potassium phosphate, calcium lactate, etc. can be used. As the coloring agent, titanium oxide, tar dyes, caramel, etc. can be used. As the preservative, methylparaben, ethylparaben, propylparaben, etc. can be used. As the fragrance, menthol, etc. can be used. Surfactants that can be used include polysorbate 80, polyoxyl 35 castor oil, etc. These may be used alone or in combination of two or more.

The content ratio of the base material constituting the soft capsule shell is not limited as long as the effects of the present invention are achieved, but for example, the plasticizer may be contained in an amount of 1 to 70 parts by mass per 100 parts by mass of the base material, with 5 to 60 parts by mass being preferred, and 10 to 50 parts by mass being more preferred.

From the viewpoint of effectively achieving liquid compatibility with the capsule shell of the oral composition, the capsule shell is preferably one whose main component is gelatin, and more preferably one containing gelatin and glycerin.

The thickness of the soft capsule shell is not limited as long as it achieves the effects of the present invention, but can be, for example, 0.001 to 2 mm, preferably 0.005 to 1.8 mm, more preferably 0.01 to 1.5 mm, even more preferably 0.05 to 1.2 mm, and particularly preferably 0.05 to 0.9 mm.

[Method of manufacturing a solid preparation] In another embodiment of the present invention, a method of manufacturing a solid preparation can be provided, which is characterized by coexisting (A) gastrointestinal herbal medicine and/or gastrointestinal anti-inflammatory repair component, (B) nonionic surfactant, and (C) hydrophobic base. The type and amount of the (A) component, the type and amount of the (B) component, and the type and amount of the (C) component are the same as those described in the [Oral composition] above. In addition, the type, etc. of the solid preparation are the same as those described in the [Dosage form] above.

The oral composition of the present invention is produced, for example, by mixing and stirring the components (A), (B), and (C), other components that are added as desired, and additives that are added as desired, by a method conventional in the art.

The device for mixing and stirring is not particularly limited, and for example, a commercially available biomixer, homojetter, or other high-speed stirrer or high-speed grinder can be used.

The oral composition of the present invention is produced by filling a capsule shell with an oral composition containing components (A), (B), and (C). The filling method is not particularly limited, and known methods such as the rotary method and the seamless method can be adopted. According to the present invention, the oral composition to be filled has more effective liquid compatibility with the capsule shell, so that the filling process can be highly controlled. For example, in the case of the rotary method, in the process of discharging the oral composition between two sheet-like capsule shells, the oral composition has good liquid compatibility, so that the oral composition is less likely to be biased, foamed, or leak. In addition, the present invention can be suitably used when designing a thin capsule shell or when designing a capsule of a micro size.

[Method for imparting an effect of improving liquid compatibility to a capsule shell] The present invention also relates to a method for imparting an effect of improving liquid compatibility to a capsule shell to an oral composition by causing (A) a gastrointestinal herbal medicine and/or a gastrointestinal anti-inflammatory repair component, (B) a nonionic surfactant, and (C) a hydrophobic base to coexist in the oral composition. The type and amount of the (A) component, the type and amount of the (B) component, and the type and amount of the (C) component are the same as those in the above-mentioned [Oral composition]. In this specification, the liquid compatibility to the capsule shell refers to the wetness at the contact surface between the capsule shell and the filled content. As an index of the liquid compatibility to the capsule shell, for example, the wetness of a droplet dropped on the capsule shell can be expressed by the magnitude of the dynamic contact angle (advancing angle). The larger the dynamic contact angle, the lower the wetness of the flowing liquid and the lower the liquid compatibility. The smaller the dynamic contact angle, the higher the wetness of the liquid flowing in contact with the capsule shell and the higher the liquid compatibility. By improving the "liquid compatibility with the capsule shell," it becomes possible to highly control the process of filling the capsule shell with the contents, which has the effect of, for example, reducing uneven filling, foaming, and liquid leakage.

[Applications] The oral composition of the present invention is suitable for use as a therapeutic, preventive, or improving agent for diseases, symptoms, and conditions for which a therapeutic effect or health-promoting effect is expected based on the pharmacological action of component (A). Examples of therapeutic and health-promoting effects based on the pharmacological action of component (A) include, but are not limited to, stomachic, anti-inflammatory, analgesic, antispasmodic, sedative, muscle relaxant, central nervous system suppressant, gastric motility promotion, intestinal motility suppressant, antibacterial, antiulcer, carminative, intestinal regulation, diuretic, choleretic, expectorant, antivomiting, antiemetic, sweating, antitussive, digestive enhancement, antipyretic, astringent, expellant, menstrual, bowel movement improvement, intestinal environment improvement, and mental stabilization. Diseases, symptoms, and conditions for which such effects are expected include, but are not limited to, stomach upset, abdominal pain, acute gastritis, chronic gastritis, acute exacerbation of chronic gastritis, diarrhea, peptic ulcers (gastric and duodenal ulcers), gastric mucosal lesions (erosions, bleeding, redness, edema), abdominal distension (abdominal bloating), upper respiratory tract inflammation such as the common cold, bronchitis, eczema (sores), allergic conjunctivitis, acute conjunctivitis, chronic conjunctivitis, keratitis, blepharitis, tonsillitis, glossitis, stomatitis, oral wounds, dysmenorrhea, constipation, joint pain, arthritis, neuralgia, neuritis, pain after surgery or trauma, etc. These diseases, symptoms, and conditions also include those that occur as side effects of ingredients used to treat, prevent, or improve another disease, symptom, or condition.

The oral composition of the present invention can be used as, for example, a pharmaceutical agent,
It can be widely used in quasi-drugs, foods, etc. The oral composition of the present invention can be provided as, but is not limited to, a specific health food, a functional food, a nutritional functional food, a food for the elderly, a special purpose food, a functional food, a dietary supplement (balanced nutritional food, supplement), or a confectionery tablet. The oral composition of the present invention also includes foods that include a package, container, package insert, instruction manual, etc. that display pharmaceutical efficacy or functionality related to health promotion. It also includes foods and beverages that display pharmaceutical efficacy or functionality related to health promotion in an application to the government, etc.

The dosage of the oral composition of the present invention is not fixed and is set appropriately depending on the form, administration method, administration purpose, and the age, weight, symptoms, and physical condition of the person to whom the composition is to be administered. Furthermore, the oral composition of the present invention may be administered once or in several divided doses per day within the desired dosage range, and may be administered before, between, or after meals, or simultaneously with meals. Note that the term "administration" is used herein with the intention of including "taking the medicine."

The oral composition of the present invention can usually be administered 1 to 6 times a day, preferably 1 to 3 times a day. Therefore, it is preferable that the oral composition of the present invention for one administration contains the amount obtained by dividing the above-mentioned daily dose by the number of times of administration per day.

Next, the present invention will be specifically explained using examples, but the present invention is not limited to the following examples.

[Test method 1: Measurement method for dynamic contact angle (advancing angle)] Using a contact angle meter DM-501 (manufactured by Kyowa Interface Science Co., Ltd.), the dynamic contact angle (advancing angle) of each liquid composition of Test Examples 1-1 to 1-13 described below was measured according to the measurement procedure of the expansion method of the contact angle meter.

Specifically, the capsule film was placed on the stage of the contact angle meter with the seamless surface facing upward. The test liquid was set in the dispenser of the contact angle meter. At room temperature, 1 μL of the test liquid was dropped onto the capsule film and allowed to settle in a hemispherical shape. Next, the tip of the liquid discharge part of the dispenser was quickly placed in the center of the upper part of the hemisphere of the test liquid. In this state, the test liquid was continuously discharged at a discharge speed of 6 μL/sec, and the shape of the droplet was photographed from the side 20 times every 0.1 seconds. If necessary, the liquid temperature was set to quickly discharge the droplet. In order to match the measurement conditions, the test liquid paired with the calculation of the liquid compatibility improvement rate was measured continuously under the same temperature conditions.

Then, the captured images were analyzed using the analysis software FAMAS of the contact angle meter, and the contact angle was obtained for each image. Here, the contact angle means the angle on the side including the test liquid, among the angle formed by the tangent drawn from the contact point P of the capsule shell surface, the test liquid, and the air to the test liquid, and the tangent drawn to the capsule shell surface. There are two contact points P, one on the left and one on the right, for each droplet. The contact angle changes due to the discharge of the test liquid, and as the droplet expands, the change in the contact angle becomes smaller. Therefore, the average value of the left and right contact angles of the droplet for each image was calculated, and the average values were arranged in the order in which the images were taken, and five consecutive contact angles were selected. The first average value when the standard deviation of the five average values first became 2.0° or less (the average value of the left and right contact angles in the image taken first out of the five average values) was used as the measured value of the dynamic contact angle in the same measurement. Note that for all test liquids, no standard deviation greater than 2.0° was observed after the standard deviation first became 2.0° or less. Even if the contact angle did not change during the droplet expansion process, the dynamic contact angle measurement was obtained according to the above criteria.

The above procedure was repeated three times for each test liquid, and the average of the three measured values was taken as the dynamic contact angle of the test liquid. The standard deviation of the three measured values was 2.0° or less for all test liquids.

[Capsule shell] The capsule shell used in test method 1 is as shown in Table 1 below. In the table for each test example, the type of capsule shell is indicated by the alphabetic symbols (a to d) shown in Table 1.

In Table 1, capsule shell a (Colgen Kowa Rhinitis Soft Mini Capsule) is a gelatin shell containing gelatin, glycerin, titanium oxide, paraben, and polysorbate 80. Capsule shell b (Rohto Alguard Rhinitis Soft Capsule EX) is a gelatin shell containing gelatin, glycerin, and titanium oxide. Capsule shell c (Daytona S) is a gelatin shell containing succinylated gelatin, concentrated glycerin, titanium oxide, and yellow ferric oxide. Capsule shell d (Estac Rhinitis Soft Varnish Cap) is a gelatin shell containing gelatin, glycerin, Blue No. 1, etc.

[Test Example 1-1] Evaluation of dynamic contact angle (advancing angle) 1 For each liquid composition shown in Table 2, the test liquid was prepared according to the procedure shown in Test Method 1 above, and immediately thereafter, the dynamic contact angle (advancing angle) was measured (average of three measured values). Of the (B) components, Poem S-100 (Riken Vitamin Co., Ltd.) was used as the glycerin fatty acid ester (same below). For the propylene glycol fatty acid ester, PMS-1CV (manufactured by Nikko Chemicals Co., Ltd.) was used (same below). For the polysorbate 80, TO-10MV (manufactured by Nikko Chemicals Co., Ltd.) was used (same below). Of the (C) components, Panacea 810 (manufactured by NOF Corporation) was used as the medium-chain fatty acid triglyceride (same below). For the soybean oil, olive oil, wheat germ oil, and camellia oil, those that fulfilled the respective items listed in the 17th Revised Japanese Pharmacopoeia or Pharmaceutical Additives Standards 2013 (same below). The liquid compatibility improvement rate of each test liquid relative to the liquid consisting only of component (C) used in each test liquid was calculated using the following [Formula 1]. The calculation results are also shown in Table 2. [Formula 1] Liquid compatibility improvement rate (%) relative to the liquid consisting only of component (C) used in each test liquid = {1 - (dynamic contact angle of each test liquid / dynamic contact angle of liquid consisting only of component (C))} x 100

As shown in Table 2, when components (B) and (C) are combined, a new problem of poor liquid compatibility was found in various combinations (Comparative Examples 1-1 to 1-14).

[Test Example 1-2] Evaluation of dynamic contact angle (advancing angle) 2 Each liquid composition was prepared according to the formulation described in Table 3. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. Of the (A) components, Magnolia Bark Powder, Atractylodes Rhizome Powder, and Citrus Thunbergii Powder were used that fulfilled the respective items of Magnolia Bark, Atractylodes Rhizome, and Citrus Thunbergii listed in the Japanese Pharmacopoeia 17th Edition or the Japanese Pharmacopoeia Standards for Crude Drugs 2015 (same below). The calculated results are also shown in Table 3.

As shown in Table 3, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Examples 2-1 to 2-6). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 2-1 to 2-6).

[Test Example 1-3] Evaluation of dynamic contact angle (advancing angle) 3 Each liquid composition was prepared according to the formulation described in Table 4. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. Of the (A) components, the fennel powder or cinnamon powder used met the respective items for fennel or cinnamon listed in the 17th Revised Japanese Pharmacopoeia or the Japanese Pharmacopoeia Standards for Crude Drugs 2015 (same below). The calculated results are also shown in Table 4.

As shown in Table 4, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Examples 3-1 to 3-4). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 3-1 to 3-4).

[Test Example 1-4] Evaluation of dynamic contact angle (advancing angle) 4 Each liquid composition was prepared according to the formulation described in Table 5. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. Of the (A) components, turmeric powder was used that met the turmeric items listed in the 17th Revised Japanese Pharmacopoeia or the Japanese Pharmacopoeia Standards for Crude Drugs 2015 (same below). The calculated results are also shown in Table 5.

As shown in Table 5, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Examples 4-1 to 4-3). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 4-1 to 4-3).

[Test Example 1-5] Evaluation of dynamic contact angle (advancing angle) 5 Each liquid composition was prepared according to the formulation shown in Table 6. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. The calculated results are also shown in Table 6.

As shown in Table 6, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Example 5-1). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 5-1 to 5-7).

[Test Example 1-6] Evaluation of dynamic contact angle (advancing angle) 6 Each liquid composition was prepared according to the formulation described in Table 7. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. Of the (A) components, rhubarb powder was used that satisfied the items for rhubarb listed in the 17th Revised Japanese Pharmacopoeia or the Japanese Pharmacopoeia Standards for Crude Drugs 2015 (same below). The calculated results are also shown in Table 7.

As shown in Table 7, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Examples 6-1 to 6-5). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 6-1 to 6-5).

[Test Example 1-7] Evaluation of dynamic contact angle (advancing angle) 7 Each liquid composition was prepared according to the formulation described in Table 8. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. Among the components (A), Phellodendron bark powder was used that satisfied the items for Phellodendron bark listed in the 17th Revised Japanese Pharmacopoeia or the Japanese Pharmacopoeia Standards for Crude Drugs 2015 (same below). The calculated results are also shown in Table 8.

As shown in Table 8, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Examples 7-1 to 7-2). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 7-1 to 7-2).

[Test Example 1-8] Evaluation of dynamic contact angle (advancing angle) 8 According to the formulation described in Table 9, each liquid composition was prepared. Among the (A) components, the dried extract of Atractylodes monadelpharma or Magnolia bark extract used was one that satisfied the items of Atractylodes monadelpharma or Magnolia bark listed in the 17th Revised Japanese Pharmacopoeia or the Japanese Pharmacopoeia Extra-Chinese Herbal Medicine Standards 2015 (hereinafter the same). The dried extract of Atractylodes monadelpharma in Table 9 is 1500 mg in terms of the amount of Atractylodes monadelpharma in raw herbal medicine, and the dried extract of Magnolia bark in Table 9 is 1000 mg in terms of the amount of Magnolia bark in raw herbal medicine. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. The calculated results are also shown in Table 9.

As shown in Table 9, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Example 8-1). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 8-1 to 8-5).

[Test Example 1-9] Evaluation of dynamic contact angle (advancing angle) 9 Each liquid composition was prepared according to the formulation shown in Table 10. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. The calculated results are also shown in Table 10.

As shown in Table 10, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Examples 9-1 to 9-3). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 9-1-1 to 9-3-2).

[Test Example 1-10] Evaluation of dynamic contact angle (advancing angle) 10 Each liquid composition was prepared according to the formulation shown in Table 11. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. The calculated results are also shown in Table 11.

As shown in Table 11, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Examples 10-1 to 10-2). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 10-1-1 to 10-2-3).

[Test Example 1-11] Evaluation of dynamic contact angle (advancing angle) 11 Each liquid composition was prepared according to the formulation shown in Table 12. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. The calculated results are also shown in Table 12.

As shown in Table 12, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Example 11-1). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 11-1 to 11-6).

[Test Example 1-12] Evaluation of dynamic contact angle (advancing angle) 12 Each liquid composition was prepared according to the formulation shown in Table 13. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. The calculated results are also shown in Table 13.

As shown in Table 13, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Example 12-1). On the other hand, quite unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 12-1 to 12-4).

[Test Example 1-13] Evaluation of dynamic contact angle (advancing angle) 13 According to the formulations shown in Tables 14 to 18, each liquid composition was prepared. The dynamic contact angle (advancing angle) was determined in the same manner as in Test Example 1-1. Among the (A) components, the onji extract, gennoshoko powder, junipera herb dried extract, swertia japonica powder, coix seed dried extract, and belladonna extract were used that fulfilled the respective items of onji, gennoshoko powder, junipera herb, swertia japonica powder, coix seed powder, or belladonna extract listed in the 17th Revised Japanese Pharmacopoeia or the Japanese Pharmacopoeia Non-Chinese Herbal Medicine Standards 2015 (same below). When the amount of the coix seed dried extract in Table 15 is expressed in terms of the amount of raw coix seed, it is 2000 mg for Comparative Example 13-5 and Example 13-5, and 6000 mg for Comparative Example 13-6 and Example 13-6. When the dried extract of Herbaceae in Table 16 is expressed in terms of the amount of Herbaceae raw herb, Comparative Example 13-11 and Example 13-11 have a content of 1500 mg, and Comparative Example 13-12 and Example 13-12 have a content of 15,000 mg. The onji extracts of Comparative Example 13-9 and Example 13-9 in Table 16 are made from 300 mg of onji. The onji extracts of Comparative Example 13-10, Example 3-10-1 and Example 3-10-2 in Table 16 are made from 3,000 mg of onji. The content of pirenzepine hydrochloride hydrate in Table 17 is the content as pirenzepine hydrochloride anhydrate. The calculated results are also shown in Tables 14 to 18.

As shown in Tables 14 to 18, it was found that when components (A) and (C) were combined, a new problem arose in that liquid compatibility deteriorated (Comparative Examples 13-1 to 13-18). On the other hand, completely unexpectedly, it was confirmed that when components (A), (B), and (C) were combined, the dynamic contact angle decreased, i.e., liquid compatibility with the capsule shell improved (Examples 13-1 to 13-18).

[Test Example 2-1] Drug release test 1 Each liquid composition was prepared according to the formulations shown in Tables 19 and 20. 7 mL of purified water was placed in a test tube, and 0.7 g of each test liquid was dropped into the tube, followed by stirring and shaking 10 times up and down. After leaving the tube to stand for 1 minute, the tube was visually observed. The evaluation criteria were as follows: × for "insoluble in water, and water and test liquid are separated", △ for "almost insoluble in water, nearly transparent, and very slightly cloudy", ○ for "part of the test liquid is dispersed, but not uniform", and ◎ for "the test liquid is uniformly dispersed and uniformly cloudy". The evaluation results are shown in Tables 19 and 20.

As shown in Tables 19 and 20, when the components (A) and (C) were combined, the liquid composition did not dissolve in water and separated (Comparative Examples 2-1-1, 2-2-1, and 2-3-1). When the components (A) and (B) were combined, the liquid composition was hardly mixed with water (Comparative Examples 2-1-2, 2-2-2, and 2-3-2). In contrast, when the components (A), (B), and (C) were combined, the liquid composition showed significantly high dispersibility (Examples 2-1-1 to 2-1-5 and Examples 2-2-1 to 2-3-1). In these examples, it was revealed that the compositions were easily mixed and dispersed in water (fast dissolution effect), had excellent drug release properties in the body (fast release effect), and were easily absorbed in the body.

[Test Example 3-1] Drug release test 2 Each liquid composition was prepared according to the formulations shown in Tables 21 to 23. The content of pirenzepine hydrochloride hydrate in Table 22 is the content as pirenzepine hydrochloride anhydrate. 7 mL of purified water was placed in a test tube, and 0.7 g of each test liquid was dropped into the test tube, and the test liquid was stirred and shaken up and down 10 times. After leaving the test liquid to stand for 1 minute, the test liquid was visually observed. The evaluation criteria were as follows: × for "insoluble in water, and water and the test liquid are separated", △ for "almost insoluble in water, almost transparent or opaque, and very slightly cloudy", ○ for "part of the test liquid is dispersed, but not uniform", and ◎ for "the test liquid is uniformly dispersed and uniformly cloudy". The evaluation results are also shown in Tables 21 to 23.

As shown in Tables 21 to 23, when the components (A) and (C) were combined, the liquid composition did not dissolve in water and separated (Comparative Examples 3-1-3, 3-1-4, 3-1-6, and 3-1-8), or the liquid composition was hardly mixed with water (Comparative Examples 3-1-1, 3-1-2, 3-1-5, 3-1-7, 3-1-9, and 3-1-10). In contrast, when the components (A), (B), and (C) were combined, the liquid composition showed significantly high dispersibility (Examples 3-1-1 to 3-1-10). In these examples, it was revealed that the compositions were easily mixed and dispersed in water (fast dissolution effect), had excellent drug release properties in the body (fast release effect), and were easily absorbed in the body.

[Manufacturing Example] Using known techniques, liquid compositions are prepared for the formulation examples shown in Tables 24 to 30, and soft capsules are manufactured. The masses in the tables are the daily doses.

Claims (9)

A capsule in which an oral composition (excluding a turmeric extract-containing composition that contains more than 40% by weight of turmeric extract and is characterized in that it is composed of medium-chain fatty acid triglycerides and/or oils and fats and/or lipophilic emulsifiers with an HLB value of 8.5 or less) containing (A) turmeric, (B) at least one nonionic surfactant selected from the group consisting of glycerin fatty acid esters, propylene glycol fatty acid esters, and POE sorbitan fatty acid esters, and (C) at least one hydrophobic base selected from the group consisting of medium-chain fatty acid triglycerides, wheat germ oil, soybean oil, camellia oil, and white beeswax (however, when component (C) is white beeswax, medium-chain fatty acid triglycerides are used in combination) is filled in a capsule shell containing gelatin. The capsule according to claim 1, wherein the content of component (A) is 0.001% by mass or more and 90% by mass or less based on the total amount of the oral composition. The capsule according to claim 1 or 2, wherein the content of component (B) is 0.1 to 80% by mass, as the total amount of component (B), based on the total amount of the oral composition. The capsule formulation according to any one of claims 1 to 3, wherein the total amount of component (B) is 0.001 to 150 parts by mass per part by mass of component (A). The capsule according to any one of claims 1 to 4, wherein the content of component (C) is 15 to 99% by mass, as the total amount of component (C), relative to the total amount of the oral composition. The capsule formulation according to any one of claims 1 to 5, wherein the total amount of component (C) is 0.01 to 300 parts by mass per part by mass of component (A). The capsule formulation according to any one of claims 1 to 6, wherein the total amount of the (C) component is 0.01 to 300 parts by mass per 1 part by mass of the total amount of the (B) component. The capsule according to any one of claims 1 to 7, wherein the daily oral dose of turmeric is 40 to 4,000 mg in terms of raw herbal drug. The capsule according to any one of claims 1 to 8, wherein the turmeric is administered orally in a single dose in an amount of 10 to 3000 mg in terms of the raw herbal drug.