Pharmaceutical compositions and production methods thereof

Abstract

To provide peony-containing pharmaceutical composition capable of preventing solidification of peony for a certain period of time due to the presence of an aluminum-containing silicon compound, as well as methods of making the same.SOLUTION: Disclosed is a pharmaceutical composition comprising peony (root of Paeonia lactiflora Pallas) and an aluminum-containing silicon compound, where the aluminum-containing silicon compound has a volume average diameter of 60 μm or less, has an apparent specific volume of 4 mL / g or more, and is contained in the composition at a content of 3 mass% or more of the total of the peony and the aluminum-containing silicon compound.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a pharmaceutical composition and a method for producing the same. More specifically, the present invention relates to a pharmaceutical composition comprising peony and a caking regulator that prevents caking of peony for a certain period of time, and a method for producing the pharmaceutical composition that contains the caking regulator and thereby prevents caking of peony for a certain period of time. [Background technology]

[0002] The Japanese Pharmacopoeia defines peony as a herbal medicine as the root of the peony root (Paeonia lactiflora Pallas), which is prepared by drying the root after scraping off the fine roots and the cork layer, and is stipulated to contain 2% or more paeoniflorin based on the dry matter of the herbal medicine. Peony root is mainly used as a Chinese herbal medicine, and is frequently mixed into prescriptions considered to be analgesics, antispasmodics, women's medicines, medicines for poor circulation, cold medicines, medicines for skin diseases, anti-inflammatory and pus-draining medicines, and other prescriptions. For example, it is prescribed in many Chinese herbal medicines such as Toki-shakuyakusan, Shimotsu-to, Keishi-bukuryo-gan, Shakuyaku-kanzo-to, and Juzen-taiho-to (see, for example, Non-Patent Document 1).

[0003] Also, in the field of pharmaceuticals, for example, sodium bicarbonate, precipitated calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium oxide, magnesium silicate, magnesium aluminosilicate, magnesium aluminometasilicate, synthetic hydrotalcite, dried aluminum hydroxide gel, synthetic aluminum silicate, magnesium alumina hydroxide, aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate co-precipitation product, aluminum hydroxide-magnesium carbonate mixed dried gel, aluminum hydroxide-magnesium carbonate-calcium carbonate co-precipitation product, borey and the like are known to be used as antacids (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 4203170 [Non-patent literature]

[0005] [Non-Patent Document 1] 17th Revised Japanese Pharmacopoeia Commentary (Hirokawa Shoten) Summary of the Invention [Problem to be solved by the invention]

[0006] When a pharmaceutical composition containing peony is produced, the peony may caking, which may make the production of the pharmaceutical composition containing peony difficult. As a result of extensive research by the inventors, it has become apparent that it is possible to prevent caking of peonies by contacting them with an aluminum-containing silicon compound having certain properties as an additive. That is, the object of the present invention is to clarify the effect of additives on preventing caking of peonies. Another object of the present invention is to provide a pharmaceutical composition containing peony, which can prevent caking of the peony for a certain period of time by including an aluminum-containing silicon compound during the production of the pharmaceutical composition, and a method for producing the same. [Means for solving the problem]

[0007] As a result of intensive research conducted by the inventors to solve the above problems, they discovered that by adding an aluminum-containing silicon compound having a certain volumetric particle size and a certain apparent specific volume to peony, it is possible to prevent caking of peony during the production of a pharmaceutical composition and to easily produce a pharmaceutical composition containing peony, and thus completed the present invention.

[0008] That is, the aspects of the present invention are as follows. (1) A pharmaceutical composition comprising peony root and an aluminum-containing silicon compound, The aluminum-containing silicon compound has a volume average diameter of 60 μm or less, The aluminum-containing silicon compound has an apparent specific volume of 4 mL / g or more; The aluminum-containing silicon compound is contained in an amount of 3 mass% or more based on the total amount of the peony and the aluminum-containing silicon compound. Pharmaceutical compositions. (2) The pharmaceutical composition according to (1), wherein the aluminum-containing silicon compound comprises at least one of magnesium aluminometasilicate and synthetic aluminum silicate. (3) The pharmaceutical composition according to (1) or (2), wherein the volume average diameter of the aluminum-containing silicon compound is 30 μm or less. (4) The pharmaceutical composition according to (3), wherein the volume average diameter of the aluminum-containing silicon compound is 0.01 μm to 20 μm. (5) The pharmaceutical composition according to any one of (1) to (4), wherein the aluminum-containing silicon compound has an apparent specific volume of 8 mL / g or more. (6) The pharmaceutical composition according to any one of (1) to (5), which comprises a mixture of the peony and the aluminum-containing silicon compound. (7) A pharmaceutical composition according to any one of (1) to (6), comprising 5% by mass or more and 85% by mass or less of the aluminum-containing silicon compound relative to the total amount of the peony and the aluminum-containing silicon compound. (8) The pharmaceutical composition according to any one of (1) to (7), which is in the form of a tablet, a fine granule, or a capsule. (9) preparing a peony and an aluminum-containing silicon compound having a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more; a contacting step of contacting the peony with 3% by mass or more of the aluminum-containing silicon compound based on the total amount of the peony and the aluminum-containing silicon compound; A method for producing a pharmaceutical composition comprising the steps of: (10) The method for producing a pharmaceutical composition according to (9), wherein the aluminum-containing silicon compound comprises at least one of magnesium aluminometasilicate and synthetic aluminum silicate. (11) The method for producing a pharmaceutical composition according to (9) or (10), wherein the volume average diameter of the aluminum-containing silicon compound is 30 μm or less. (12) The method for producing a pharmaceutical composition according to any one of (9) to (11), wherein the aluminum-containing silicon compound has an apparent specific volume of 8 mL / g or more. (13) A method for producing a pharmaceutical composition according to any one of (9) to (12), wherein in the contacting step, the peony is contacted with the aluminum-containing silicon compound in an amount of 5% by mass or more and 85% by mass or less based on the total amount of the peony and the aluminum-containing silicon compound. (14) A pharmaceutical composition produced by the method for producing a pharmaceutical composition according to any one of (9) to (13). Effect of the Invention

[0009] According to the pharmaceutical composition and the production method thereof of the present invention, a peony-containing pharmaceutical composition can be obtained that can prevent caking of the peony for a certain period of time during the production of the pharmaceutical composition, and the peony-containing pharmaceutical composition can be easily produced. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The pharmaceutical composition of the present invention comprises peony and an aluminum-containing silicon compound, wherein the volume average diameter of the aluminum-containing silicon compound is 60 μm or less, the apparent specific volume of the aluminum-containing silicon compound is 4 mL / g or more, and the aluminum-containing silicon compound is contained in an amount of 3 mass% or more relative to the total amount of the peony and the aluminum-containing silicon compound.

[0011] The method for producing the pharmaceutical composition of the present invention includes a preparation step of preparing a peony and an aluminum-containing silicon compound having a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more, and a contact step of contacting the peony with at least 3 mass% of the aluminum-containing silicon compound relative to the total amount of the peony and the aluminum-containing silicon compound.

[0012] <Peony> "Peony" is the root of the peony (Paeonia lactiflora Pallas), prepared by drying the root after scraping off the fine roots and the cork layer, and is stipulated to contain 2% or more paeoniflorin based on the dry matter of the herb. "Shakuyaku (peony)" is listed in the 17th revised edition of the Japanese Pharmacopoeia. Shakuyaku is both the name of a herbal medicine (Japanese Pharmacopoeia) and the name of a plant.

[0013] As the peony, those listed in the 17th revised edition of the Japanese Pharmacopoeia can be preferably used. Other peonies than those mentioned above are also available commercially and are easily available.

[0014] Peony has been used medicinally since ancient times as a single ingredient or as a traditional Chinese medicine, and the herbal powder or extract obtained according to a conventional method can be used as it is. The powdered herbs or extracts may be in the form of ordinary commercially available products or processed products thereof. For example, dried, chopped, processed herbal powders may be further pulverized into powder form (fine powder form) to be used as the powdered herbs. The form of the component extracted from the crude drug is not particularly limited, and any form such as a dry extract, extract powder, soft extract, liquid extract, tincture containing ethanol or ethanol and water can be used.

[0015] Preferred herbal medicines include extract components that have a high degree of freedom in formulation, such as dried extract powders. The extract components can be obtained by conventional methods, such as extracting active ingredients having antibacterial activity from the herbal medicines using an extraction solvent. As the extraction solvent, for example, a hydrophilic solvent such as water or ethanol, or a mixture thereof, may be used.

[0016] In the present invention, the peony is exemplified by the case where "dried peony extract (ratio of raw herb equivalent: 7:1 (7 times concentrated peony))" is used. In other words, "containing 3% or more by mass of the aluminum-containing silicon compound relative to the total amount of the peony and the aluminum-containing silicon compound" means "containing 3% or more by mass of the aluminum-containing silicon compound relative to the total amount of the dried peony extract and the aluminum-containing silicon compound."

[0017] For example, when converting the amount of peony dry extract into the amount of peony in terms of raw herbal medicine, a coefficient corresponding to the concentration rate of the extract may be multiplied. For example, if peony dry extract is equivalent to a 7-fold concentrated peony, then 7 times the amount of peony dry extract is equivalent to the amount of peony raw herb.

[0018] Although the example in which a dried peony extract is used as the peony has been shown, the above-mentioned herbal powder or extract component may also be used, for example, a soft peony extract may also be used. When using a herbal powder or extract component other than dried peony extract as the peony, appropriate conditions can be set to prevent the peony from caking (for example, changing the ratio of peony to aluminum-containing silicon compound depending on the concentration of the peony in terms of its original herbal drug), and the peony in this invention is not limited to "dried peony extract."

[0019] In this specification, the "equivalent amount of raw herbal medicine" refers to the mass (dry mass) of raw herbal medicine required to obtain the amount of the ingredient. In the case of peony itself, the mass of peony to be mixed is the equivalent amount of raw herbal medicine, and in the case of peony extract (dried peony extract, soft peony extract, etc.), the dry mass of raw herbal medicine (peony) required to obtain the amount of peony extract to be mixed is the equivalent amount of raw herbal medicine. Although there is no particular limitation on the type of peony dried extract, examples of commercially available peony dried extract include Peony Dried Extract manufactured by Nippon Powder Pharmaceutical Co., Ltd. (product name: Peony Dried Extract-Q, extraction solvent: water, crude drug equivalent ratio of 7:1 (peony concentrated 7 times)) and Peony Dried Extract manufactured by Alps Pharmaceutical Co., Ltd. (extraction solvent: water, crude drug equivalent ratio of 5:1 (peony concentrated 5 times)). Furthermore, the peony soft extract is not particularly limited, but examples of commercially available peony soft extracts include peony soft extract manufactured by Nippon Powder Pharmaceutical Co., Ltd. (product name: Peony Dried Extract-A, extraction solvent: water, raw drug equivalent ratio 4:1 (peony is four times concentrated)) and peony extract manufactured by Alps Pharmaceutical Co., Ltd. (extraction solvent: water, raw drug equivalent ratio 4:1 (peony is four times concentrated)).

[0020] <Aluminum-containing silicon compounds> The aluminum-containing silicon compound in the present invention is a compound containing aluminum and silicon. As the aluminum-containing silicon compound in the present invention, for example, magnesium aluminometasilicate, aluminum silicate, synthetic aluminum silicate, magnesium aluminometasilicate, magnesium aluminum silicate, and bentonite may be used. The aluminum-containing silicon compound in the present invention preferably contains at least one of magnesium aluminometasilicate and synthetic aluminum silicate. The aluminum-containing silicon compound in the present invention has a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more. In the present invention, by using the above-mentioned "aluminum-containing silicon compound having a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more" as a caking regulator, it is possible to prevent caking of the peony for a certain period of time during the production process of the peony-containing pharmaceutical composition, and when the pharmaceutical product such as a tablet is produced, a stable pharmaceutical product can be obtained. The aluminum-containing silicon compound of the present invention may be used as an additive in a pharmaceutical composition, or may be used as an antacid (first antacid) as described below. In addition, the caking control agent in the present invention refers to "an aluminum-containing silicon compound having a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more," and is capable of preventing caking of peonies for a certain period of time, for example, during the production process of a peony-containing pharmaceutical composition. Furthermore, at least one type of aluminum-containing silicon compound may satisfy the above-mentioned characteristic "volume average diameter is 60 μm or less and apparent specific volume is 4 mL / g or more." In other words, even when multiple types of aluminum-containing silicon compounds are present in the pharmaceutical composition, at least one type may satisfy the above-mentioned characteristic "volume average diameter is 60 μm or less and apparent specific volume is 4 mL / g or more."

[0021] [Average particle size (volume average diameter)] The average particle size in this specification is a result of measurement by a laser diffraction / scattering method, and is defined as a volume average size. Specifically, as described in the Examples section below, the volume average diameters described in this specification are values ​​evaluated by dry measurement using an MT3300EXII manufactured by Microtrac-Bell Corporation. In addition, the average particle diameter (volume average diameter) in this specification indicates, as an example, a value obtained by a laser diffraction / scattering method, but may be a value measured by any other known particle diameter measuring method or particle diameter measuring device.

[0022] [Apparent specific volume (static specific volume)] In this specification, the apparent specific volume is a value calculated by putting a sample into a 100 mL measuring cylinder with a funnel to make the volume 90 to 100 mL, and flattening the surface of the sample, and calculating V / W as the volume (V mL) and the mass (W g) of the sample.

[0023] The aluminum-containing silicon compound as the caking regulator preferably contains at least one of magnesium aluminometasilicate and synthetic aluminum silicate. In other words, it is preferable that the aluminum-containing silicon compound serving as the caking regulator contains at least one of magnesium aluminometasilicate and synthetic aluminum silicate, which satisfy the requirements of a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more.

[0024] As the caking control agent, magnesium aluminometasilicate having a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more is more preferable. When magnesium aluminometasilicate with a volume mean diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more was used as a caking agent, the caking of peonies was prevented for a longer period of time than when synthetic aluminum silicate was used.

[0025] In the pharmaceutical composition of the present invention, the volume average diameter of the aluminum-containing silicon compound is 60 μm or less, preferably 30 μm or less, more preferably 0.01 μm to 20 μm, and even more preferably 1 μm to 15 μm. When the volume average diameter of the aluminum-containing silicon compound is 60 μm or less, the aluminum-containing silicon compound adheres uniformly to the surfaces of the peony particles, and contact between the peony particles is suppressed.

[0026] In the present invention, the apparent specific volume of the aluminum-containing silicon compound is 4 mL / g or more, preferably 8 mL / g or more, and more preferably 8 mL / g to 30 mL / g. If the aluminum-containing silicon compound has a bulkiness with an apparent specific volume of 4 mL / g or more, when the aluminum-containing silicon compound is mixed with peony, contact between the peony particles is suppressed.

[0027] The aluminum-containing silicon compound is preferably one whose surface has been neutralized. When the surface of the aluminum-containing silicon compound has been neutralized, for example, a slurry of the aluminum-containing silicon compound (e.g., a 4% slurry of the aluminum-containing silicon compound) is prepared, and the slurry exhibits neutrality (e.g., pH 6 to 8). If the surface of the aluminum-containing silicon compound has been neutralized, the aluminum-containing silicon compound can preferably prevent caking of the peony when mixed with the peony.

[0028] The aluminum-containing silicon compound has a specific surface area (BET specific surface area) of 250 m 2 / g or more, and 280m 2 / g or more is more preferable, and 280 to 700m 2 It is more preferable that the molecular weight is / g. The aluminum-containing silicon compound has a specific surface area (BET specific surface area) of 250 m 2 When the aluminium-containing silicon compound is more than 1 / g, the anti-caking effect of the peony can be suitably obtained when the peony is mixed with the aluminium-containing silicon compound.

[0029] Furthermore, the aluminum-containing silicon compound preferably has a moisture content of 12 wt % or less, more preferably 10 wt % or less, further preferably 8 wt % or less, and particularly preferably 7 wt % or less. If the moisture content of the aluminum-containing silicon compound is 12 wt % or less, the effect of preventing caking of the peony can be suitably obtained when the aluminum-containing silicon compound is mixed with the peony.

[0030] <Peony-containing pharmaceutical composition and method for producing peony-containing pharmaceutical composition> The pharmaceutical composition of the present invention comprises peony and an aluminum-containing silicon compound, wherein the aluminum-containing silicon compound has a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more, and contains 3 mass% or more of the aluminum-containing silicon compound relative to the total amount of the peony and the aluminum-containing silicon compound. In addition, the method for producing the pharmaceutical composition of the present invention includes a preparation step of preparing peony and an aluminum-containing silicon compound having a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more, and a contact step of contacting the peony with at least 3 mass% of the aluminum-containing silicon compound relative to the total amount of the peony and the aluminum-containing silicon compound. In addition, as for peony, a case where a dried extract of peony is used is exemplified. In other words, in the present invention, "containing 3% or more by mass of the aluminum-containing silicon compound relative to the total amount of the peony and the aluminum-containing silicon compound" means "containing 3% or more by mass of the aluminum-containing silicon compound relative to the total amount of the dried peony extract and the aluminum-containing silicon compound."

[0031] According to the pharmaceutical composition having the above-mentioned configuration and the method for producing the pharmaceutical composition, caking of the peony can be prevented for a certain period of time during the production of the peony-containing pharmaceutical composition.

[0032] Specifically, when peony (e.g., dried peony extract) is left exposed to the air, the peony will harden in less than about 1.5 hours due to factors such as absorption of moisture in the air. If the peony hardens, it will form clumps during the production of medicines and other products using the peony as a raw material, resulting in uneven distribution of the peony in the medicine. Furthermore, the peony content in the pharmaceutical product varies, making it virtually impossible to obtain the desired pharmaceutical product.

[0033] On the other hand, in the present invention, caking of the peony is prevented by preparing a pharmaceutical composition so that it contains 3% by mass or more of "aluminum-containing silicon compound having a volume average diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more" relative to the total amount of the peony and the aluminum-containing silicon compound.

[0034] Specifically, in the present invention, by satisfying "characteristic (1): the volume average diameter of the aluminum-containing silicon compound is 60 μm or less" and "characteristic (2): the apparent specific volume of the aluminum-containing silicon compound is 4 mL / g or more", the particle size of the aluminum-containing silicon compound is fine, and the mixture of the aluminum-containing silicon compound and peony is likely to be bulky, and the particle size of the aluminum-containing silicon compound is fine, so that the number of particles adhering to the peony is increased, and the contact area between the peonies is reduced. As a result, the pharmaceutical composition of the present invention, by satisfying both "characteristic (1)" and "characteristic (2)", can obtain a suitable caking suppression effect on the peony. Specifically, the pharmaceutical composition of the present invention containing peony and a caking regulator can prevent caking of peony for 1.5 hours or more when exposed to the air.

[0035] Furthermore, the pharmaceutical composition of the present invention can prevent caking of peony for 1.5 hours or more, which allows sufficient time to be secured in pharmaceutical production and prevents peony from being unevenly distributed in the desired drug or pharmaceutical product, facilitating the production of further pharmaceutical compositions, pharmaceutical products, etc. using the peony-containing pharmaceutical composition as a raw material.

[0036] In the present invention, the peony may be in contact with at least a part of the aluminum-containing silicon compound, and it is preferable that the peony and the aluminum-containing silicon compound are mixed together. In other words, when producing a pharmaceutical composition containing peony root and an aluminum-containing silicon compound, it is preferable to prepare the pharmaceutical composition so as to mix peony root and the aluminum-containing silicon compound. By having a composition in which peonies and an aluminum-containing silicon compound are mixed, the aluminum-containing silicon compound adheres uniformly to the surfaces of the peony particles, and caking of the peonies is suitably prevented.

[0037] In the present invention, the aluminum-containing silicon compound is preferably contained in an amount of 5 mass% or more and 85 mass% or less of the total amount of the peony and the aluminum-containing silicon compound, more preferably 5 mass% or more and 80 mass% or less of the aluminum-containing silicon compound, may be contained in an amount of 5 mass% or more and 70 mass% or less of the aluminum-containing silicon compound, may be contained in an amount of 5 mass% or more and 60 mass% or less of the aluminum-containing silicon compound, or may be contained in an amount of 5 mass% or more and 50 mass% or less of the aluminum-containing silicon compound, based on the total amount of the peony and the aluminum-containing silicon compound. By including 5% by mass or more and 85% by mass or less of the aluminum-containing silicon compound relative to the total amount of the peony and the aluminum-containing silicon compound, caking of the peony is prevented, and a more sufficient time, for example, 2 hours or more, can be secured when manufacturing a pharmaceutical product using a pharmaceutical composition containing the peony. Furthermore, according to a pharmaceutical composition containing 5% by mass or more and 85% by mass or less of an aluminum-containing silicon compound relative to the total amount of peony and the aluminum-containing silicon compound, when a pharmaceutical product such as a tablet is manufactured using the pharmaceutical composition, the tablet is preferably formed. In other words, according to the present invention, caking of peonies is appropriately prevented when a pharmaceutical composition is produced, and when a pharmaceutical product is produced using the pharmaceutical composition, the pharmaceutical product can be appropriately produced.

[0038] The pharmaceutical composition of the present invention contains peony root and an aluminum-containing silicon compound, and may further contain other ingredients.

[0039] The pharmaceutical composition of the present invention may be used, for example, as a herbal medicine, an analgesic and antispasmodic drug, a medicine for women, a medicine for poor circulation, a medicine for colds, a medicine for skin diseases, or an anti-inflammatory and draining drug. Paeoniflorin, the main component of peony, is known to have analgesic, antispasmodic, anti-inflammatory, peripheral vasodilator, and muscle contraction inhibitory effects. Peony is used in Chinese herbal medicines such as Shakuyaku-kanzo-to, Toki-shakuyaku-san, Keishi-to, and Bofu-tsusho-san to treat symptoms such as lower back pain, cramps, heavy head, and menstrual pain, and is also sometimes used as an ingredient in Western medicine combinations. The pharmaceutical composition of the present invention may also be used, for example, as an antipyretic, analgesic, or cold remedy. Furthermore, the pharmaceutical composition of the present invention may be, for example, a tablet, fine granule, or capsule. A pharmaceutical composition containing peony and an aluminum-containing silicon compound may be used to prepare, for example, a pharmaceutical composition as shown below.

[0040] There is also no particular limitation on the amount of peony contained in the pharmaceutical composition of the present invention, but the amount of the ingredient contained in the pharmaceutical composition per dosage unit (daily dosage) for adults may be 100 to 5000 mg, preferably 150 to 2000 mg, more preferably 200 to 1660 mg, and even more preferably 200 to 900 mg, in terms of the amount of raw herbal medicine, and the frequency of administration is 1 to 3 times a day.

[0041] The pharmaceutical composition of the present invention may be used in Shakuyaku-kanzo-to, which contains peony extract (eg, dried peony extract) and licorice extract (eg, dried licorice extract) as medicinal ingredients. In addition, the present invention also makes it possible to make Shakuyaku-kanzo-to, which is generally in the form of fine granules or granules, into tablets.

[0042] The pharmaceutical composition of the present invention may be used for the purpose of suppressing fever, pain, and inflammation. It is preferably used for pain relief from headache, menstrual pain (period pain), toothache, pain after tooth extraction, sore throat, lower back pain, joint pain, muscle pain, stiff shoulder pain, earache, bruise pain, bone fracture pain, sprain pain, trauma pain, etc., and for fever reduction during chills and fever. In addition, an analgesic component and an antipyretic component (antipyretic analgesic) may be added to the pharmaceutical composition of the present invention as a cold treatment agent for the purpose of relieving various cold symptoms (runny nose, stuffy nose, cough, phlegm, sore throat, fever, chills, headache, sneezing, joint pain, muscle pain).

[0043] Specifically, the pharmaceutical composition of the present invention can contain one or more antipyretic and analgesic ingredients selected from the group consisting of aspirin, aspirin aluminum, acetaminophen, ethenzamide, sazapirin, salicylamide, lactylphenetidine, ibuprofen, isopropylantipyrine, rofecoxib sodium hydrate, prazolam, diclofenac sodium, mefenamic acid, indomethacin farnesyl, acemetacin, etodolac, naproxen, meloxicam, celecoxib, and tiaramide hydrochloride.

[0044] The pharmaceutical composition of the present invention may be in the dosage form described in the General Provisions for Preparations of the Japanese Pharmacopoeia, 17th Edition, etc., such as solid preparations such as tablets (including chewable tablets, effervescent tablets, orally disintegrating tablets, etc.), troches, drops, hard capsules, soft capsules, granules, fine granules, powders, pills, dry syrup, suppositories, poultices, and plasters; semi-solid preparations such as lozenges, chewing gums, jellies, jelly-like drops, whipped creams, ointments, creams, foams, inhalers, and nasal gels; and liquid preparations such as syrups, drinks, suspensions, spirits, liquids, eye drops, aerosols, sprays, and sprays.

[0045] From the viewpoints of ease of administration and manufacturing aspects, the pharmaceutical composition of the present invention is preferably a solid preparation, more preferably an oral pharmaceutical composition selected from the group consisting of tablets, capsules, pills, granules, powders and fine granules, and particularly preferably a tablet or capsule.

[0046] The pharmaceutical composition of the present invention may further contain other active ingredients, as necessary, such as antitussives / expectorants, antihistamines, anti-inflammatory agents, gastrointestinal ingredients, antacids, anticholinergic agents, sedatives, other vitamins, and xanthine derivatives within the scope of the present invention. If there are any contraindications for inclusion of these ingredients, the composition may be formulated by dividing the ingredients into granules or the like.

[0047] The antitussive / expectorant may contain one or more components selected from, for example, codeine, codeine phosphate hydrate, dihydrocodeine, dihydrocodeine phosphate, dibunate sodium, dimemorphan phosphate, tipepidine citrate, tipepidine hibenzate, dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthaline salt, noscapine hydrochloride, trimetoquinol hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, ambroxol hydrochloride, bromhexine hydrochloride, and the like.

[0048] As the antihistamine, for example, one or more components selected from azelastine hydrochloride, alimemazine tartrate, ebastine, epinastine hydrochloride, emedastine fumarate, oxatomide, olopatadine hydrochloride, carbinoxamine, clemastine fumarate, diphenyl disulfonate, carbinoxamine maleate, d-chlorpheniramine maleate, dl-chlorpheniramine maleate, ketotifen fumarate, diphenylpyraline hydrochloride, diphenylpyraline theoclate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, triprolidine hydrochloride, tripelennamine hydrochloride, thonzylamine hydrochloride, fexofenadine, fenethazine hydrochloride, promethazine hydrochloride, promethazine, mequitazine, methdilazine hydrochloride, loratadine, etc. may be blended.

[0049] As the anti-inflammatory agent, one or more components selected from glycyrrhizinic acid and its derivatives and salts thereof (eg, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.), tranexamic acid, etc. may be blended.

[0050] As the gastrointestinal drug component, one or more components selected from gefarnate, cetraxate hydrochloride, sofalcone, teprenone, methylmethionine sulfonium chloride, etc. can be blended.

[0051] As for the antacid, the above-mentioned aluminum-containing silicon compound (caking regulator) may be used as the first antacid. As for the antacid, in addition to the first antacid (the aluminum-containing silicon compound), an antacid different from the aluminum-containing silicon compound may be used separately as a second antacid. For example, the antacid in the pharmaceutical composition of the present invention may consist solely of the first antacid (the above aluminum-containing silicon compound). Furthermore, when a first antacid (the above aluminum-containing silicon compound) and a second antacid are used in combination as antacids in the pharmaceutical composition of the present invention, the ratio of the first antacid to the second antacid is not particularly limited, and for example, the "ratio of first antacid:second antacid" may be, in mass ratio, 1:99 to 99:1, 3:97 to 97:3, or 4:96 to 96:4. For example, in the pharmaceutical composition of the present invention, an aluminum-containing silicon compound (caking regulator) may be used as an additive, and a second antacid may be used as the antacid.

[0052] The antacid of the present invention may be appropriately selected taking into consideration the prevention of caking of the peony, its function as an antacid, manufacturability, and the like. For example, by using a first antacid (the above-mentioned aluminum-containing silicon compound) in combination with a second antacid, it is possible to reduce the burden caused by caking during the production of a peony-containing pharmaceutical composition while maintaining its function as an antacid in tablets.

[0053] The second antacid is an antacid different from the aluminum-containing silicon compound (caking regulator). Examples of the second antacid include inorganic salts of metals selected from magnesium, aluminum, and calcium, such as magnesium silicate, magnesium aluminate silicate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, co-precipitation product of magnesium hydroxide and aluminum potassium sulfate, magnesium carbonate, synthetic hydrotalcite, magnesium aluminate metasilicate, dried aluminum hydroxide gel, synthetic aluminum silicate, 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, magnesium carbonate, and calcium carbonate, bentonite, calcium silicate, calcium carbonate, precipitated calcium carbonate, calcium hydrogen phosphate, and anhydrous calcium hydrogen phosphate. Examples of the alkali metal basic inorganic compound include inorganic salts of metals selected from sodium and potassium, such as dry sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium carbonate hydrate, sodium hydrogen phosphate hydrate, anhydrous sodium monohydrogen phosphate, potassium hydroxide, potassium bicarbonate, potassium carbonate, and others include borax and glycine, etc. The second antacid can contain one or more components selected from these.

[0054] Among these, magnesium oxide, magnesium aluminometasilicate, synthetic aluminum silicate, precipitated calcium carbonate and glycine are particularly preferred as the second antacid.

[0055] In the present invention, for example, magnesium aluminometasilicate and synthetic aluminum silicate are treated as the first antacid when they satisfy both of the conditions of "property (1): the volume average diameter is 60 μm or less" and "property (2): the aluminum-containing silicon compound has an apparent specific volume of 4 mL / g or more" in "the above aluminum-containing silicon compound." In addition, in the present invention, for example, when magnesium aluminometasilicate and synthetic aluminum silicate do not satisfy at least one of the conditions of "property (1): the volume average diameter is 60 μm or less" and "property (2): the aluminum-containing silicon compound has an apparent specific volume of 4 mL / g or more" in "the above aluminum-containing silicon compound," they are treated as a second antacid.

[0056] As the anticholinergic agent, one or more ingredients selected from scopolamine hydrobromide, Datura extract, methylscopolamine bromide, methyl-l-hyoscyamine bromide, pirenzepine hydrochloride, butylscopolamine bromide, belladonna alkaloids, belladonna extract, belladonna total alkaloids, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, Scolytsum extract, Scolytsum root, and Scolytsum root total alkaloid citrate may be blended.

[0057] As the sedative, one or more components selected from bromvalerylurea, allylisopropylacetylurea, etc. may be blended.

[0058] As for vitamins, one or more ingredients selected from vitamin A, vitamin C, vitamin B1, vitamin B2, vitamin B6, vitamin B5, vitamin B12, vitamin P, hesperidin, vitamin D, vitamin E, nicotinic acid, nicotinamide, panthenol, calcium pantothenate, sodium pantothenate, biotin, a mixture of equal parts of potassium and magnesium aspartate, inositol hexanicotinate, ursodeoxycholic acid, L-cysteine, L-cysteine ​​hydrochloride, orotin, gamma-oryzanol, calcium glycerophosphate, calcium gluconate, gluconolactone, glucuronic acid amide, sodium chondroitin sulfate, carrot, and coix seed can be blended.

[0059] As the xanthine derivative, one or more components selected from caffeine hydrate, anhydrous caffeine, sodium caffeine benzoate, and caffeine citrate can be blended.

[0060] The pharmaceutical composition of the present invention can be formulated in accordance with conventional methods. The method for producing the pharmaceutical composition of the present invention is not limited to the method shown below. For example, Shakuyaku-kanzo-to and antipyretic analgesics can be produced by the method shown below.

[0061] <Shakuyaku-kanzoto> For example, when the pharmaceutical composition is Shakuyaku-kanzo-to, plain tablets of Shakuyaku-kanzo-to can be produced by the following methods of Step 1A and Step 2A. [Step 1A]: Peony (for example, dried peony extract) and an aluminum-containing silicon compound are mixed to obtain a triturated product. [Step 2A]: The triturated product prepared in Step 1A, the dried licorice extract, and any additives required for forming uncoated tablets are taken and prepared into uncoated tablets according to the tablet manufacturing method prescribed in the General Provisions of Preparations of the Japanese Pharmacopoeia.

[0062] <Antipyretics and analgesics> For example, when the pharmaceutical composition is an antipyretic analgesic, uncoated tablets of the antipyretic analgesic can be produced by the following methods of Step 1B and Step 2B. In addition, optionally, the uncoated tablets obtained in step 2B can be subjected to the method of step 3B to produce film-coated tablets of the antipyretic analgesic drug. [Step 1B]: Peony (for example, dried peony extract) and an aluminum-containing silicon compound are mixed to obtain a triturated product. [Step 2B]: The triturated product prepared in Step 1B, any active ingredient (e.g., an antipyretic analgesic ingredient), and any additives required for forming uncoated tablets are taken and prepared into uncoated tablets according to the General Provisions for Preparations of the Japanese Pharmacopoeia and the tablet manufacturing method. [Step 3B]: The plain tablets obtained in step 2B are coated with a coating component (e.g., hypromellose, titanium oxide, macrogol, etc.) and then polished with carnauba wax to produce film-coated tablets.

[0063] The formulation can be prepared by using known methods and additives as appropriate. Additives may be added as appropriate within the range that does not impair the effects of the present invention. Examples of additives include excipients, disintegrants, lubricants, coating agents, binders, flow agents, plasticizers, sugar-coating agents, gloss agents, solvents, pH regulators, colorants, flavorings, sweeteners, flavorings, flavorings, and flavorings.

[0064] Examples of excipients include crystalline cellulose, powdered cellulose, potato starch, light anhydrous silicic acid, hydrated silicon dioxide, silicon dioxide, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, magnesium oxide, calcium lactate, calcium silicate, magnesium aluminometasilicate, synthetic hydrotalcite, synthetic aluminum silicate, lactose, sucrose, D-mannitol, erythritol, glucose, fructose, and the like.

[0065] Examples of disintegrants include carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropylcellulose, crospovidone, alginic acid, partially pregelatinized starch, bentonite, and the like.

[0066] Examples of lubricants include magnesium stearate, calcium stearate, talc, sucrose fatty acid esters, glycerin fatty acid esters, polyethylene glycol, and hardened oils.

[0067] Examples of coating agents include aminoalkyl methacrylate copolymers, gum arabic, ethyl cellulose, carnauba wax, carboxyvinyl polymers, magnesium stearate, shellac, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, pullulan, povidone, polyvinyl alcohol, and macrogol.

[0068] The binder may be, for example, one or more components selected from gum arabic, powdered gum arabic, agar, powdered agar, plum powder, gelatin, shellac, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, pullulan, povidone, polyvinyl alcohol, methacrylic acid copolymer L, methacrylic acid copolymer, butyl methacrylate-methyl methacrylate copolymer, methyl cellulose, etc.

[0069] The fluidizing agent may be, for example, one or more components selected from hydrous silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, heavy anhydrous silicic acid, magnesium alumina hydroxide, calcium triphosphate, talc, magnesium aluminometasilicate, calcium hydrogen phosphate granules, etc.

[0070] As the plasticizer, one or more components selected from triethyl citrate, glycerin, glycerin fatty acid esters, medium-chain fatty acid triglycerides, triacetin, concentrated glycerin, castor oil, propylene glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polysorbate 80, macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, glycerin monostearate, isopropyl linoleate, liquid paraffin, etc. can be blended.

[0071] The sugar-coating agent may be one or more components selected from gum arabic, powdered gum arabic, ethyl cellulose, carnauba wax, carmellose sodium, titanium oxide, stearic acid, polyoxyl 40 stearate, purified gelatin, purified shellac, refined white sugar, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, white sugar, hydroxypropyl cellulose, hypromellose, pullulan, povidone, polyoxyethylene, polyvinyl alcohol, macrogol, etc.

[0072] As the glossing agent, one or more components selected from carnauba wax, refined shellac, macrogol, beeswax, etc. can be blended.

[0073] As the solvent, one or more components selected from isopropanol, ethanol, glycerin, 1,3-butylene glycol, propylene glycol, macrogol, and the like can be blended.

[0074] The pH adjuster may be one or more components selected from hydrochloric acid, acetic acid, phosphoric acid, lactic acid, citric acid, succinic acid, tartaric acid, sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, triethanolamine, etc.

[0075] As colorants, one or more components selected from yellow iron oxide, brown iron oxide, carbon black, caramel, β-carotene, licorice extract, black iron oxide, titanium oxide, yellow ferric oxide, ferric oxide, ferric oxide-glycerin suspension, food blue No. 2 aluminum lake, food yellow No. 4 aluminum lake, sodium copper chlorophyllin, riboflavin, riboflavin butyrate, riboflavin sodium phosphate, green tea powder, rose oil, etc. may be blended.

[0076] Flavoring agents include sodium chloride, Phellodendron bark powder, Phellodendron extract, Coptis chinensis, Coptis chinensis powder, orange, orange oil, cocoa powder, fructose, caramel, licorice, licorice extract, licorice powder, xylitol, calcium citrate, citric acid hydrate, sodium citrate hydrate, L-glutamic acid, sodium L-glutamate, grapefruit extract, brown sugar, cinnamon powder, cinnamon oil, saccharin, sodium saccharin hydrate, Japanese pepper powder, tartaric acid, D-tartaric acid, potassium hydrogen tartrate, DL-sodium tartrate, and ginger. It can contain one or more ingredients selected from the following: sucralose, stevia extract, purified stevia extract, Swertia jasmine, D-sorbitol, tannic acid, clove oil, tincture, chili pepper, chili pepper powder, spruce powder, trehalose hydrate, bittern powder, plum extract, fructooligosaccharides, powdered sugar, peppermint powder, D-mannitol, dl-menthol, l-menthol, menthol powder, ryunou, ryunou powder, green tea powder, DL-malic acid, DL-sodium malate, lemon oil, rose oil, etc.

[0077] As sweeteners, one or more ingredients selected from aspartame, acesulfame potassium, amacha, amacha powder, reduced maltose syrup, licorice, licorice extract, licorice powder, xylitol, dipotassium glycyrrhizinate, disodium glycyrrhizinate, saccharin, sodium saccharin hydrate, sucralose, stevia extract, purified stevia extract, refined white sugar, fructose, white sugar, maltitol, D-mannitol, erythritol, etc. may be blended.

[0078] The flavoring may be one or more ingredients selected from orange flavor, guarana extract, sweet orange, strawberry, brown sugar flavor, strawberry flavor, cherry flavor, banana powder flavor, peach essence, fruit essence, peppermint, melon powder flavor, l-menthol, peppermint oil, etc.

[0079] Flavoring agents and fragrances include: fennel powder, fennel oil, ethyl vanillin, orange, orange extract, orange essence, orange oil, chamomile oil, caramel, licorice powder, d-camphor, dl-camphor, cinnamon powder, cinnamon oil, citronella oil, sugar flavor, spearmint oil, cherry flavor, clove oil, chili flavor, spruce tincture, spruce oil, pine oil, peppermint oil, vanilla flavor, vanillin, bitter essence, and Vitabase. It can contain one or more ingredients selected from the following: Himalayan cedar oil, fruit flavor, flavor G1, hesperidin peppermint essence, bergamot oil, vermouth flavor, d-borneol, dl-borneol, matcha, mixed flavor, mint flavor, dl-menthol, l-menthol, eucalyptus oil, lavender oil, ryunou, ryunou powder, lemon powder, lemon oil, rose water, rose oil, and peppermint oil.

[0080] These additives are not limited to those listed above, and one of these may be used alone or two or more of them may be used in combination.

[0081] The pharmaceutical composition of the present invention may be once packaged in SP packaging, PTP packaging, stick packaging, bottle packaging, etc. and then stored airtight. These may then be pillow-packaged, or stored in a box or the like. The material used for the pillow packaging is not particularly limited, and may be, for example, a resin film such as a polypropylene film, a polyethylene terephthalate film, or a polyethylene film, or a resin film with aluminum foil attached thereto. If hygroscopicity is a concern, a desiccant or the like may be stored simultaneously in the bottle packaging or pillow packaging.

[0082] The present invention will be described in more detail below with reference to examples and formulation examples, but the present invention is not limited to these examples. EXAMPLES

[0083] <Experiment 1: Examination of the anti-caking effect of aluminum-containing silicon compounds on peony root> [Example 1] As the aluminum-containing silicon compound, magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd.: product name Neusilin UFL2, apparent specific volume (catalog value): 9.0 to 18.0 mL / g) was used. The particle size of the magnesium aluminometasilicate (Neusilin UFL2) used in Example 1 was measured. The particle size of the magnesium aluminometasilicate (Neusilin UFL2) used in Example 1 was measured using an MT3300EXII manufactured by Microtrack Bell Corporation, and evaluation was performed by dry measurement. As a result, the volume mean diameter (MV) of the magnesium aluminometasilicate (Neusilin UFL2) used in Example 1 was 6.73 μm. The apparent specific volume of magnesium aluminometasilicate (Neusilin UFL2) according to Example 1 was measured by putting a sample into a 100 mL measuring cylinder using a funnel so that the volume was 90 to 100 mL, and the volume (V mL) when the surface of the sample was flattened and the mass (W g) of the sample was defined as V / W. The apparent specific volume of the magnesium aluminometasilicate (Neusilin UFL2) used in this Example 1 was measured and found to be 10.2 mL / g. The peony used was dried peony extract manufactured by Nippon Powder Pharmaceutical Co., Ltd. (product name: dried peony extract-Q, an extract of peony concentrated 7 times). 0.3 g of magnesium aluminometasilicate (Neusilin UFL2) and 9.7 g of dried peony extract were mixed to prepare a mixed powder. In addition, each mixed powder obtained was stored for 1.5 hours under hygroscopic conditions at 25°C and 75% RH. Furthermore, the presence or absence of caking in the mixed powder at the time point of 1.5 hours was determined by visual inspection and by shaking the mixture. In addition, when the peonies were caking, it was judged that the peonies were caking when the mixture did not move even when shaken, in addition to visual judgment.

[0084] [Example 2] The mixed powder in Example 2 was examined for the presence or absence of caking in the mixed powder in the same manner as in Example 1, except that 0.5 g of magnesium aluminometasilicate (Neusilin UFL2) and 9.5 g of dried peony extract were mixed to prepare a mixed powder.

[0085] [Comparative Example 1] The mixed powder in Comparative Example 1 was examined for the presence or absence of caking in the mixed powder in the same manner as in Example 1, except that 0.1 g of magnesium aluminometasilicate (Neusilin UFL2) and 9.9 g of dried peony extract were mixed to prepare a mixed powder.

[0086] [Comparative Example 2] As the aluminum-containing silicon compound in Comparative Example 2, magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd.: product name Neusilin S1, apparent specific volume (catalog value): 2.7 to 3.3 mL / g) was used. The magnesium aluminometasilicate (Neusilin S1) used in Comparative Example 2 was subjected to particle size measurement and particle size distribution measurement. The particle size of the magnesium aluminometasilicate (Neusilin S1) used in Comparative Example 2 was measured using the MT3300EXII manufactured by Microtrack Bell Corporation in the same manner as in Example 1, and evaluation was performed by dry measurement. As a result, the volume mean diameter (MV) of magnesium aluminometasilicate (Neusilin S1) used in Comparative Example 2 was 66.85 μm. In addition, the apparent specific volume of the magnesium aluminometasilicate (Neusilin S1) used in Comparative Example 2 was measured using a method similar to that used in Example 1, and the apparent specific volume of the magnesium aluminometasilicate (Neusilin S1) used in Comparative Example 2 was 3.0 mL / g. In Comparative Example 2, 0.1 g of magnesium aluminometasilicate (Neusilin S1) and 9.9 g of dried peony extract were mixed to prepare a mixed powder. The procedure was otherwise the same as in Example 1, and the presence or absence of caking of the mixed powder in Comparative Example 2 was confirmed.

[0087] [Comparative Example 3] In Comparative Example 3, 0.3 g of magnesium aluminometasilicate (Neusilin S1) and 9.7 g of dried peony extract were mixed to prepare a mixed powder. The procedure was otherwise the same as in Comparative Example 2, and the presence or absence of caking of the mixed powder in Comparative Example 3 was confirmed.

[0088] [Comparative Example 4] In Comparative Example 4, 0.5 g of magnesium aluminometasilicate (Neusilin S1) and 9.5 g of dried peony extract were mixed to prepare a mixed powder. The procedure was otherwise the same as in Comparative Example 2, and the presence or absence of caking of the mixed powder in Comparative Example 4 was confirmed.

[0089] [Comparative Example 5] As the aluminum-containing silicon compound in Comparative Example 5, magnesium aluminometasilicate (manufactured by Fuji Chemical Industry Co., Ltd.: product name Neusilin US2, apparent specific volume (catalog value) 5.5 to 7.5 mL / g) was used. The magnesium aluminometasilicate (Neusilin US2) used in Comparative Example 5 was subjected to particle size measurement and particle size distribution measurement. The particle size of the magnesium aluminometasilicate (Neusilin US2) used in Comparative Example 5 was measured using the MT3300EXII manufactured by Microtrack Bell Corporation in the same manner as in Example 1, and evaluation was performed by dry measurement. As a result, the volume mean diameter (MV) of magnesium aluminometasilicate (Neusilin US2) used in Comparative Example 5 was 62.96 μm. In addition, the apparent specific volume of the magnesium aluminometasilicate (Neusilin US2) used in Comparative Example 5 was measured using a method similar to that used in Example 1, and the apparent specific volume of the magnesium aluminometasilicate (Neusilin US2) used in Comparative Example 5 was 5.8 mL / g. In Comparative Example 5, 0.1 g of magnesium aluminometasilicate (Neusilin US2) and 9.9 g of dried peony extract were mixed to prepare a mixed powder. The procedure was otherwise the same as in Example 1, and the presence or absence of caking of the mixed powder in Comparative Example 5 was confirmed.

[0090] [Comparative Example 6] In Comparative Example 6, 0.3 g of magnesium aluminometasilicate (Neusilin US2) and 9.7 g of dried peony extract were mixed to prepare a mixed powder. The procedure was the same as in Comparative Example 5, and the presence or absence of caking of the mixed powder in Comparative Example 6 was confirmed.

[0091] [Comparative Example 7] In Comparative Example 7, 0.5 g of magnesium aluminometasilicate (Neusilin US2) and 9.5 g of dried peony extract were mixed to prepare a mixed powder. The procedure was the same as in Comparative Example 5, and the presence or absence of caking of the mixed powder in Comparative Example 7 was confirmed.

[0092] [Judgment results for the presence or absence of caking of peonies] The results of Examples 1 and 2 and Comparative Examples 1 to 7 are shown in Table 1. The evaluation criteria for the evaluation results in Table 1 are as follows: A: Caking of peonies was effectively prevented. B: Most of the caking of peonies was prevented, and some caking occurred. C: The caking of peonies could not be prevented.

[0093] [Table 1]

[0094] As shown in Table 1, from the results of Examples 1 and 2 and Comparative Example 1, which used magnesium aluminometasilicate (Neusilin UFL2) with an apparent specific volume (actual value) of 10.2 mL / g (apparent specific volume (catalog value): 9.0 to 18.0 mL / g) and a volume mean diameter (MV) of 6.73 μm, it was observed that when the amount of magnesium aluminometasilicate (Neusilin UFL2) was 0.1 g per 9.9 g of dried peony extract, caking of the peony did not tend to be sufficiently prevented. In addition, when the amount of magnesium aluminometasilicate (Neusilin UFL2) per 9.7 g of dried peony extract is 0.3 g or more, caking of the peony tends to be prevented. In other words, when the amount of magnesium aluminometasilicate (Neusilin UFL2) is 3 mass% or more based on the total amount of dried peony extract and magnesium aluminometasilicate (Neusilin UFL2), caking of the peony tends to be prevented. In addition, it was confirmed that the mixed powder of magnesium aluminometasilicate (Neusilin UFL2) and peony dried extract in Example 2, which contains a higher amount of magnesium aluminometasilicate (Neusilin UFL2), tends to be better prevented from caking than the mixed powder in Example 1.

[0095] When magnesium aluminometasilicate (Neusilin S1) having an apparent specific volume (actual value) of 3.0 mL / g (apparent specific volume (catalog value): 2.7 to 3.3 mL / g) and a volume mean diameter (MV) of 66.85 μm was used as in Comparative Examples 2 to 4, the caking of the peony was not prevented for any of the mixed powders in which 1 to 5 mass% of magnesium aluminometasilicate (Neusilin S1) was mixed with respect to the total amount of dried peony extract and magnesium aluminometasilicate (Neusilin S1). Furthermore, when magnesium aluminometasilicate (Neusilin US2) with an apparent specific volume (actual value) of 5.8 mL / g (apparent specific volume (catalog value): 5.5 to 7.5 mL / g) and a volume mean diameter (MV) of 62.96 μm was used as in Comparative Examples 5 to 7, the mixed powders in which 1 to 5 mass% of magnesium aluminometasilicate (Neusilin US2) was mixed with respect to the total amount of dried peony extract and magnesium aluminometasilicate (Neusilin US2) were unable to prevent caking of the peony.

[0096] According to the results of Experiment 1, caking of the peony tended to be prevented when magnesium aluminometasilicate having an average volume diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more was mixed in an amount of 3 mass% or more relative to the total amount of peony dried extract and magnesium aluminometasilicate.

[0097] <Experiment 2: Examination of the types of additives in the anti-caking effect of peony root> Next, in order to examine the anti-caking effect of additives on peony in more detail, the additives were changed in type and their effects on peony were confirmed. The additives used in Experiment 2 were compounds used as antacid ingredients in pharmaceutical compositions, or compounds used as flow agents or excipients, similar to magnesium aluminometasilicate. The additives used in Experiment 2 are shown in Table 2.

[0098] [Table 2]

[0099] [Example 3] As in Example 1, the additive in Example 3 was magnesium aluminometasilicate sample No. 1, an aluminum-containing silicon compound (manufactured by Fuji Chemical Industry Co., Ltd.: product name Neusilin UFL2, apparent specific volume (catalog value) 9.0 to 18.0 mL / g, apparent specific volume (actual value) 10.2 mL / g, volume mean diameter (MV): 6.73 μm). As in Example 1, dried peony extract (product name: dried peony extract-Q, an extract of peony concentrated 7 times) manufactured by Nippon Powder Pharmaceutical Co., Ltd. was used as the peony. 0.1 g (equivalent to 5% by mass based on the total mass of peony and additive) of sample No. 1 additive was added to 1.9 g of peony dry extract, and the peony dry extract and sample No. 1 additive were mixed. The obtained mixture was allowed to stand in an environment of 25°C and 60% RH, and the presence or absence of caking was judged by visual observation and shaking the mixture at 1 hour, 1.5 hours, and 2 hours after the start of the test. The caking of the peonies was judged to be determined by visual inspection and when the mixture did not move even when shaken. In this example, the following examples, and the comparative examples, the following indices were used for the anti-caking effect of peony. A: Prevention of caking of peonies was confirmed up to 2 hours after the start of the test. B: Prevention of caking of peonies was confirmed up to 1.5 hours after the start of the test. C: Caking of the peonies was confirmed 1.5 hours after the start of the test. The results of Example 3 are shown in Table 3. In Table 3 below, "-" indicates that the data was not measured.

[0100] [Example 4] The additive used in sample No. 2 was synthetic aluminum silicate (Kyowa Chemical Industry Co., Ltd.: grade characteristics). The particle size of the synthetic aluminum silicate used in Example 4 was measured. The particle size of the synthetic aluminum silicate (specialty) used in Example 4 was measured using the MT3300EXII manufactured by Microtrack Bell Corporation in the same manner as in Example 1, and evaluation was performed by dry measurement. As a result, the volume mean diameter (MV) of the synthetic aluminum silicate (specialty) used in Example 4 was 11.04 μm. Furthermore, the apparent specific volume of synthetic aluminum silicate was measured using the same procedure as in Example 1, and the apparent specific volume of "Sample No. 2: synthetic aluminum silicate" used in Example 4 was 5.4 mL / g. An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 2 was used, and the anti-caking effect of the mixed powder in Example 4 was confirmed. The results of Example 4 are shown in Table 3.

[0101] [Comparative Example 8] The additive for sample No. 3 was magnesium aluminometasilicate similar to that used in Comparative Example 5 (manufactured by Fuji Chemical Industry Co., Ltd.: product name Neusilin US2, apparent specific volume (catalog value) 5.5 to 7.5 mL / g, apparent specific volume (actual value) 5.8 mL / g, volume mean diameter (MV): 62.96 μm). An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 3 was used, and the anti-caking effect of the mixed powder in Comparative Example 8 was confirmed. The results of Comparative Example 8 are shown in Table 3.

[0102] [Comparative Example 9] The additive for sample No. 4 was magnesium aluminometasilicate similar to that used in Comparative Example 2 (manufactured by Fuji Chemical Industry Co., Ltd.: product name Neusilin S1, apparent specific volume (catalog value): 2.7 to 3.3 mL / g, apparent specific volume (actual value): 3.0 mL / g, volume mean diameter (MV): 66.85 μm). An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 4 was used, and the anti-caking effect of the mixed powder in Comparative Example 9 was confirmed. The results of Comparative Example 9 are shown in Table 3.

[0103] [Comparative Example 10] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 5 was used, and the anti-caking effect of the mixed powder in Comparative Example 10 was confirmed. The results of Comparative Example 10 are shown in Table 3.

[0104] [Comparative Example 11] An experiment was conducted in the same manner as in Example 3, except that the additive of Sample No. 6 (magnesium aluminosilicate, Neusilin A AS manufactured by Fuji Chemical Industry Co., Ltd., apparent specific volume (catalog value) 2.3 to 3.3 mL / g) was used, and the anti-caking effect of the mixed powder in Comparative Example 11 was confirmed. In addition, the volume mean diameter (MV) of the additive of sample No. 6 (magnesium aluminosilicate, Neusilin A AS manufactured by Fuji Chemical Industry Co., Ltd.) was measured in the same manner as in Example 1, and the volume mean diameter (MV) of the additive of sample No. 6 (magnesium aluminosilicate, Neusilin A AS manufactured by Fuji Chemical Industry Co., Ltd.) was 35.68 μm. The apparent specific volume of the additive of sample No. 6 (magnesium aluminosilicate, Neusilin A AS manufactured by Fuji Chemical Industry Co., Ltd.) was measured in the same manner as in Example 1. The apparent specific volume of the additive of sample No. 6 (magnesium aluminosilicate, Neusilin A AS manufactured by Fuji Chemical Industry Co., Ltd.) used in Comparative Example 11 was 2.6 mL / g. The results of Comparative Example 11 are shown in Table 3.

[0105] [Comparative Example 12] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 7 was used, and the anti-caking effect of the mixed powder in Comparative Example 12 was confirmed. The results of Comparative Example 12 are shown in Table 3.

[0106] [Comparative Example 13] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 8 was used, and the anti-caking effect of the mixed powder in Comparative Example 13 was confirmed. The results of Comparative Example 13 are shown in Table 3.

[0107] [Comparative Example 14] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 9 was used, and the anti-caking effect of the mixed powder in Comparative Example 14 was confirmed. The results of Comparative Example 14 are shown in Table 3.

[0108] [Comparative Example 15] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 10 was used, and the anti-caking effect of the mixed powder in Comparative Example 15 was confirmed. The results of Comparative Example 15 are shown in Table 3.

[0109] [Comparative Example 16] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 11 was used, and the anti-caking effect of the mixed powder in Comparative Example 16 was confirmed. The results of Comparative Example 16 are shown in Table 3.

[0110] [Comparative Example 17] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 12 was used, and the anti-caking effect of the mixed powder in Comparative Example 17 was confirmed. The results of Comparative Example 17 are shown in Table 3.

[0111] [Comparative Example 18] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 13 was used, and the anti-caking effect of the mixed powder in Comparative Example 18 was confirmed. The results of Comparative Example 18 are shown in Table 3.

[0112] [Comparative Example 19] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 14 was used, and the anti-caking effect of the mixed powder in Comparative Example 19 was confirmed. The results of Comparative Example 19 are shown in Table 3.

[0113] [Comparative Example 20] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 15 was used, and the anti-caking effect of the mixed powder in Comparative Example 20 was confirmed. The results of Comparative Example 20 are shown in Table 3.

[0114] [Comparative Example 21] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 16 was used, and the anti-caking effect of the mixed powder in Comparative Example 21 was confirmed. The results of Comparative Example 21 are shown in Table 3.

[0115] [Comparative Example 22] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 17 was used, and the anti-caking effect of the mixed powder in Comparative Example 22 was confirmed. The results of Comparative Example 22 are shown in Table 3.

[0116] [Comparative Example 23] An experiment was carried out in the same manner as in Example 3, except that the additive of Sample No. 18 was used, and the anti-caking effect of the mixed powder in Comparative Example 23 was confirmed. The results of Comparative Example 23 are shown in Table 3. In Table 3, the apparent specific volume and the volume average diameter are shown when they were actually measured, and the catalogue values ​​are shown when they were not actually measured.

[0117] [Table 3]

[0118] In addition, Examples 3 and 4 and Comparative Examples 8 to 23 shown in Table 3 all show the results of preparing mixed powders so that the additives shown in each example were 5 mass% relative to the total mass of peony and additives.

[0119] As shown in Table 3, in Example 3, which used additive No. 1 magnesium aluminometasilicate (Neusilin UFL2) with an apparent specific volume (actual value) of 10.2 mL / g (apparent specific volume (catalog value): 9.0 to 18.0 mL / g) and a volume mean diameter (MV) of 6.73 μm, caking of peonies was prevented for up to 2 hours from the start of the test, and an excellent caking prevention effect was obtained. In addition, in Example 4, which used additive No. 2, synthetic aluminum silicate (extra light), which had an apparent specific volume (actual measured value) of 5.4 mL / g and a volume mean diameter (MV) of 11.04 μm, caking of the peonies was prevented for 1.5 hours from the start of the test, and a caking prevention effect second only to Example 3 was obtained.

[0120] On the other hand, when magnesium aluminometasilicate (Neusilin US2) with an apparent specific volume greater than 4 mL / g but a volume mean diameter (MV) greater than 60 μm was used, as in Comparative Example 8, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test. Furthermore, when magnesium aluminometasilicate (Neusilin S1) with an apparent specific volume less than 4 mL / g and a volume mean diameter (MV) greater than 60 μm was used, as in Comparative Example 9, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0121] When dry aluminum hydroxide gel (sample No. 5), a compound not containing silicon, was used as in Comparative Example 10, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0122] When magnesium aluminosilicate (sample No. 6) having a volume average diameter of 60 μm or less but an apparent specific volume of less than 4 mL / g was used as in Comparative Example 11, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0123] When magnesium silicate (sample No. 7), a compound not containing aluminum, was used as in Comparative Example 12, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0124] When synthetic hydrotalcite (sample No. 8), a compound that does not contain silicon but contains aluminum and magnesium, was used as in Comparative Example 13, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0125] When magnesium oxide (sample No. 9), a compound not containing silicon or aluminum, was used as in Comparative Example 14, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0126] When magnesium hydroxide (sample No. 10), a compound not containing silicon or aluminum, was used as in Comparative Example 15, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0127] In the cases of Comparative Examples 16 and 17 in which precipitated calcium carbonate (Sample No. 11) and anhydrous calcium hydrogen phosphate (Sample No. 12), which are not aluminum-containing silicon compounds, were used, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0128] When light anhydrous silicic acid (samples Nos. 13 to 16), which is a silicon compound that does not contain aluminum, was used as in Comparative Examples 18 to 21, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0129] When cyclodextrin (sample No. 17) was used as in Comparative Example 22, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0130] When talc (sample No. 18), a compound containing magnesium and silicon but not aluminum, was used as in Comparative Example 23, caking of the mixed powder containing peony was confirmed 1.5 hours after the start of the test.

[0131] From the above results, the results of Experiment 2 clarified that caking of peonies tends to be prevented by mixing peonies with an aluminum-containing silicon compound having an average volume diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more. Furthermore, the results of Comparative Examples 8 to 23 revealed that when the average volume diameter was greater than 60 μm and the apparent specific volume was less than 4 mL / g, even silicon compounds containing aluminum tended not to prevent caking of peonies. Furthermore, the results of Comparative Examples 8 to 23 revealed that when a compound not containing both silicon and aluminum was used as an additive, caking of peonies tended not to be prevented.

[0132] <Experiment 3> In experiment 3, we also investigated the case where the amount of additive was greater than that of peony.

[0133] [Example 5] The mixed powder in Example 5 was examined for the presence or absence of caking in the mixed powder in the same manner as in Example 1, except that 7.37 g of magnesium aluminometasilicate (Neusilin UFL2) and 2.63 g of dried peony extract were mixed to prepare a mixed powder.

[0134] [Comparative Example 24] The mixed powder in Comparative Example 24 was examined for the presence or absence of caking in the mixed powder in Comparative Example 24, except that 7.37 g of magnesium aluminometasilicate (Neusilin S1) and 2.63 g of dried peony extract were mixed to prepare a mixed powder, in the same manner as in Comparative Example 2.

[0135] [Judgment results for the presence or absence of caking of peonies] The results of Example 5 and Comparative Example 24 are shown in Table 4. The criteria for judging the evaluation results in Table 4 are as follows: A: Caking of peonies was effectively prevented. B: Most of the caking of peonies was prevented, and some caking occurred. C: The caking of peonies could not be prevented.

[0136] [Table 4]

[0137] According to the results of Experiment 3, even when magnesium aluminometasilicate (Neusilin UFL2), which is a magnesium aluminometasilicate with an average volume diameter of 60 μm or less and an apparent specific volume of 4 mL / g or more, was mixed at 73.7 mass% of the total amount of peony dried extract and magnesium aluminometasilicate (Neusilin UFL2), caking of the peony tended to be prevented. On the other hand, when magnesium aluminometasilicate (Neusilin S1) with an apparent specific volume (actual value) of 3.0 mL / g (apparent specific volume (catalog value): 2.7 to 3.3 mL / g) and a volume mean diameter (MV) of 66.85 μm was used as in Comparative Example 24, even the mixed powder mixed at 73.7 mass% of the total amount of peony dried extract and magnesium aluminometasilicate (Neusilin S1) could not prevent caking of the peony.

[0138] (Formulation Examples 1-6 (Shakuyaku-kanzo-to)) [Process 1A] The dried peony extract is mixed with magnesium aluminometasilicate and triturated to obtain the composition shown in Table 5. [Process 2A] The triturated product prepared in Step 1A and the six components listed in Table 5, from the licorice dried extract to magnesium stearate, are prepared into the uncoated tablets of Formulation Example 1 according to the General Provisions for Preparations of the Japanese Pharmacopoeia and the tablet manufacturing method, so as to have the composition shown in Table 5. In addition, uncoated tablets according to Formulation Examples 2 and 3 are prepared in the same manner as in Formulation Example 1 so as to have the compositions shown in Table 5. In addition, uncoated tablets according to Formulation Examples 4 to 6 are prepared to have the compositions shown in Table 5 in the same manner as in Formulation Example 1, except that magnesium aluminometasilicate is replaced with synthetic aluminum silicate.

[0139] (Formulation Examples 7 to 12 (Antipyretic Analgesic)) [Process 1B] The dried peony extract is mixed with magnesium aluminometasilicate or synthetic aluminium silicate to obtain the composition shown in Table 5, and then triturated. [Process 2B] Take the triturated product prepared in step 1B and each of the components listed in Table 5, from ibuprofen to calcium stearate, and prepare uncoated tablets according to the General Provisions of Preparations in the Japanese Pharmacopoeia and the tablet manufacturing method so as to have the composition shown in Table 5. [Process 3B] Furthermore, the plain tablets obtained in step 2B are coated with the three components from hypromellose to macrogol 400, and then polished with carnauba wax to produce film-coated tablets according to Formulation Example 7 having the composition shown in Table 5. In addition, film-coated tablets according to Formulation Examples 8 to 12 are prepared in the same manner as in Formulation Example 7 so as to have the compositions shown in Table 5.

[0140] [Table 5] JPEG2025074264000006.jpg206170

[0141] Although the preferred embodiments and examples of the present invention have been described above, the present invention is not limited to these. Addition, omission, substitution, and other modifications of the configuration are possible without departing from the spirit of the present invention. [Industrial Applicability]

[0142] The pharmaceutical composition containing peony and aluminum-containing silicon compound of the present invention is extremely useful since it can prevent caking of peony for a certain period of time and therefore can prevent caking of peony during pharmaceutical production. Furthermore, the pharmaceutical composition containing the peony and the aluminum-containing silicon compound of the present invention can be used, for example, as an analgesic and antispasmodic drug, a women's drug, a drug for poor circulation, a cold medicine, a drug for skin diseases, an anti-inflammatory and draining drug, an antipyretic, an analgesic, or a cold treatment drug. As an antipyretic or an analgesic drug, it is particularly suitable for use in relieving pain from headaches, menstrual pain (period pain), toothache, pain after tooth extraction, sore throat, lower back pain, joint pain, muscle pain, stiff shoulders, earache, bruises, bone fracture pain, sprains, and trauma pain, and for reducing fever during chills and fever. It can also be used as a cold treatment drug in medicines that are preferably used to relieve various cold symptoms (runny nose, stuffy nose, cough, phlegm, sore throat, fever, chills, headache, sneezing, joint pain, and muscle pain).

Claims

1. A method for preventing caking of peonies, comprising contacting peonies with an aluminum-containing silicon compound in an amount of 3 mass% or more relative to the total amount of the peony and the aluminum-containing silicon compound, wherein the aluminum-containing silicon compound has a volume average diameter of 60 μm or less and an apparent specific volume of 8 mL / g or more.

2. 2. The method for preventing caking of peonies according to claim 1, wherein caking of peonies is prevented for 1.5 hours or more when exposed to the atmosphere.

3. 3. The method for preventing caking of peonies according to claim 1 or 2, wherein the aluminum-containing silicon compound comprises at least one of magnesium aluminometasilicate and synthetic aluminum silicate.

4. 4. The method for preventing caking of peonies according to claim 1, wherein the volume average diameter of the aluminum-containing silicon compound is 30 μm or less.

5. 5. The method for preventing caking of peonies according to claim 4, wherein the volume average diameter of the aluminum-containing silicon compound is 0.01 μm to 20 μm.

6. 6. A method for preventing caking of peonies according to claim 1, wherein the aluminum-containing silicon compound is contacted with the peony in an amount of 5% by mass or more and 85% by mass or less based on the total amount of the peony and the aluminum-containing silicon compound.

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