JP4803969B2 - Method for producing granules containing plant extract - Google Patents

Description

  The present invention relates to a method for producing granules, and more particularly to a method for producing powders, granules or fine granules containing a plant extract. Furthermore, this invention relates to the various preparations using the granule obtained by the said manufacturing method, and the said granule.

  In general, granulation operations used for the manufacture of granules (including powders, granules and fine granules) in the pharmaceutical field mainly include “extrusion granulation method”, “fluidized bed granulation method”, and “ There are three methods of “agitation granulation”. Among them, the “extrusion granulation method” that is most widely used is usually performed through steps of blending, mixing, kneading, granulating, drying, granulating, and sieving as shown in the flowchart of FIG.

Of these steps, water is usually used as a solvent in the kneading liquid used in kneading, but since a small amount of water is used (usually several percent with respect to the mixed powder). ), It is not uniformly dispersed throughout the kneaded product, and the viscosity of water is strong, so the resistance to the granulator (granulator) increases with time during granulation, or it generates heat. There's a problem. When this tendency is strong, there are cases where the granulator stops operating or the cylinder (or disk) of the granulator is damaged and production is stopped. For this reason, as a method for reducing the viscosity of water and improving the dispersibility of water, a method of using a mixed solution obtained by adding ethanol to water as a kneaded solution has been proposed (see Non-Patent Document 1). ).
PHARM TECH JAPAN, Vol.16, No.6, May, 2000, pp.40-49

  The present inventors used the above-mentioned mixed liquid of water and ethanol as a kneading liquid when granulating using a highly viscous raw material such as an extract of a plant using an extrusion granulation method. Even in this case, it has been found that there is a problem that the increase in viscosity and mechanical resistance during kneading and granulation cannot be eliminated.

  An object of the present invention is to provide a method for eliminating an increase in viscosity and mechanical resistance during kneading or granulation in the production of a granule containing a plant extract as a raw material using an extrusion granulation method. That is. Another object of the present invention is to provide a method for efficiently producing a granule containing a plant extract by eliminating an increase in viscosity and mechanical resistance during kneading or granulation. is there. Furthermore, this invention aims at providing the formulation of the various forms prepared using the granule obtained by this method, and the said granule.

  The inventors of the present invention have been diligently studied to solve the above problems, and by using water, ethanol and menthol as a kneading liquid used for kneading, a viscous plant extract was used as a raw material. Even in this case, it was found that thickening over time at the time of kneading is suppressed, and granules having a desired size can be granulated stably and continuously.

The present invention has been developed based on such findings, and has the following aspects:
Item 1. The manufacturing method of the plant extract containing granule which has the process of granulating by extrusion granulation, after adding water, ethanol, and menthol as a kneading liquid to the mixed powder containing a plant extract and kneading.
Item 2. Item 2. The method for producing a plant extract-containing granule according to Item 1, wherein ethanol containing water and menthol is used as the kneading liquid.
Item 3. The plant extract is Akamegashiwa, Fennel, Uyaku, Ages, Ezoukogi, Engosaku, Enmeiso, Ogon, Ouaku, Spruce, Ouren, Onji, Ganju, Licorice, Oyster, Pheasant, Kyonin, Kokushi, Keihi, Gentiana, Genko , Gomin, Psycho, Saishin, Sankirai, Hawthorn, Sanshishi, Salamander, Elephant, Peonies, Shazenso, Zyuyaku, Shoyo, Senega, Senkyu, Assembly, Sojitsu, Soyo, Daiou, Taiso, Chimpi, Toki, Tokon, Nantenjitsu, Carrot An extract of at least one botanical herbal medicine selected from the group consisting of Bakmondo, Bakkujutsu, Buttonpi, Hop, Maou, Mokko, Yokuinin, Ryutan, and Rotokon That method of plant extract-containing granules as described in claim 1 or 2.
Item 4. Item 3. A method for producing a plant extract-containing granule according to Item 1 or 2, wherein the plant extract is an extract of peony.
Item 5. Item 5. A plant extract-containing granule produced by the method according to any one of Items 1 to 4.
Item 6. Akamegashiwa, Fennel, Uyaku, Ages, Ezoukogi, Engosaku, Enmeiso, Ogon, Oubak, Spruce, Ouren, Onji, Gakutsu, Licorice, Oyster, Pheasant, Kyonin, Kokushi, Keihi, Gentiana, Ginseng, Kojin, Kojin, Kojin Sankirai, Hawthorn, Saishin, Sanshishi, Salamander, Giant, Peonies, Shazenso, Zyuyaku, Shoyo, Senega, Senkyu, Assembly, Suzutsu, Yoyo, Daiou, Taiso, Chimpi, Toki, Tokon, Nantenjitsu, Carrot, Bakumondo, Syrup At least 2 weights of at least one botanical herbal extract selected from the group consisting of Buttonpi, Hop, Maoh, Mokko, Yokuinin, Ryutan and Rotokon Wherein a ratio of, and proper amount of water a plant extract-containing granules is 0.5 to 10 wt%.
Item 7. A plant extract-containing granule having an appropriate water content of 0.5 to 10% by weight, which is prepared by using, as a raw material, mixed powder containing peonies extract at a ratio of at least 2% by weight, water, ethanol, and menthol .
Item 8. Item 8. A capsule or coated granule containing the plant extract-containing granule according to any one of Items 5 to 7 therein.
Item 9. Item 8. A tablet prepared using the plant extract-containing granule according to any one of Items 5 to 7.

The present invention is described in detail below.
(1) The manufacturing method of a plant extract containing granule, and the granule obtained by this The present invention provides the manufacturing method by extrusion granulation of the granule containing a plant extract.

  Here, the granules targeted by the present invention include powders, granules, fine granules, and dry syrups. Granules and fine granules are preferred.

  In addition, the granules of the present invention can be used as they are in the form of granules (for example, granules or fine granules) (use as “preparations” themselves), sugar-coated granules, enteric granules, etc. Used as core particles of coated granules whose surface is coated with sugar or other coating agent as in (Use of coated granules as core particles: granules for coating), capsule base material Used as a raw material granule for filling into tablets (use as a “capsule raw material”: granule for capsule production), and used as a raw material granule in tablet production (for example, wet granule compression method) (Use as “tablet raw material”: granules for tableting).

  When the granules are used as preparations, especially as granules, the final granules should be tested using the following particle size tests using No. 10 (1700 μm), No. 12 (1400 μm) and No. 42 (355 μm) sieves. When done, the entire volume of No. 10 (1700μm) sieve is passed through, the remaining amount of No. 12 (1400μm) sieve is 5% or less of the total volume, and the passing volume of No. 42 (355μm) sieve is 15% or less of the total volume. It is preferable that More preferably, it is a granule that passes through a No. 10 (1700 μm) sieve and a No. 12 (1400 μm) sieve in total, and the No. 42 (355 μm) sieve passes through 5% or less of the total quantity. Particularly preferably, when a particle size test is performed using a No. 30 (500 μm) sieve, the residue of the No. 30 (500 μm) sieve is almost 100% of the total amount (that is, the No. 30 (500 μm) sieve passes through the sieve). 0).

  In addition, when using granules, especially as powders, the following particle size tests were conducted using granules No. 18 (850 μm), No. 30 (500 μm) and No. 200 (75 μm) sieves. In this case, it is preferable that the total amount of No. 18 (850 μm) sieve passes through, and the residual amount of No. 30 (500 μm) sieve is 5% or less of the total amount (in this case, it passes through No. 200 (75 μm) sieve) However, granules with 10% or less of the total amount can be called fine granules). More preferably, it is a granule that passes through the No. 18 (850 μm) sieve and No. 30 (500 μm) sieve for powders, and the No. 18 (850 μm) sieve and No. 30 (500 μm) sieve for fine granules. It is a granule that passes through the No. 200 (75 μm) sieve and is less than 5% of the total amount.

<Particle size test> (From the Japanese Pharmacopoeia, General Formulation “7. Granules”)
Accurately measure this product (20.0 g for granules, 10.0 g for powders), place it in the upper sieve of the device with the above sieve and receiver stacked, cover the top and leave for 3 minutes After swirling occasionally while shaking, weigh each sieve and receiver residue. However, the inner diameter of the sieve frame used in this test shall be 75 mm.

  In addition, the plant extract used in the present invention is particularly used as a component for pharmaceutical use, food use, cosmetic use or feed use, and is preferably processed as a granule by the method of the present invention. There is no particular limitation.

  Suitable examples of such plant extracts include Akamegashiwa, Fennel, Uyaku, Ages, Ezokogi, Engosaku, Enmeiso, Ogon, Ouaku, Ouhi, Ouren, Onji, Gajutsu, Licorice, Oyster, Pheasant, Kyonin, Kokushi, Keihi, Gentian, Gennoshouko, Kojin, Koboku, Gomin, Psycho, Saishin, Sankirai, Hawthorn, Sanshishi, Salamander, Giant, Peonies, Shazenso, Juyaku, Shoyo, Senega, Senkyu, Senburi, Suzutsu, Soyo, Daio, Taiso, Chichi, Toki Name extracts of herbal medicines such as Tokon, Nantenjitsu, Carrot, Bacmond, Sandalwood, Buttonpi, Hops, Maoh, Mokko, Yokuinin, Ryutan, or Rotokon It can be. In the present invention, as the plant extract, one kind of plant extract may be used alone, or two or more plant extracts may be used in combination.

  Here, Akamegasiwa is the bark of the fallen leaves of Euphorbiaceae (Euphorbiaceae) and Akamegasiwa (Mallotus japonicus (Thunb.) Muell. Arg.). Used for improving treatment of duodenal ulcer. Akamegasiwa is both a herbal medicine (Japanese Pharmacopoeia) and a plant name.

  Fennel (Umbell) is a perennial herb of Umbelliferae, a fruit of Feniculum vulgare Muller, and is mainly used as a herbal medicine (Japanese Pharmacopoeia) for aromatic healthy stomach. In addition, fennel is both a herbal medicine name (Japanese Pharmacopoeia) and a plant name.

  Uyaku is the root of the evergreen shrub of the Lauraceae family, Lindera strychnifolia (Sieb. Et Zucc.) F. Vill., And is a herbal medicine (Japanese pharmacopoeia exogenous drug standard) with an aromatic healthy stomach and analgesia. As well as for the treatment of improving excitement, abdominal pain, anti-gastric nausea, frequent urination and headache.

  Ages are false fruits (including flower beds, fruit stalks and appendages of fruits, etc.) or fruits (true nuts) of roses (Rosa multiflora Tbunberg) or other related plants (Rosaceae), It is mainly used as a crude drug (Japanese Pharmacopoeia) for laxatives.

  Ezoukogi is the root bark of Acanthopanax senticosus Harms (Eleutherococcus senticocus Maxim), a deciduous shrub of the family Argiaceae, and is also called “Gokahi”, mainly for anti-fatigue, anti-stress, blood circulation promotion, etc. Used for applications.

  Engosaku is a tuber of the poppy family (Corydalis turtschaninovii Besser forma yanhusuo YH / Chou et CC Hsu,) or its related plant (Papaveranceae), and is mainly used as a crude drug (Japanese Pharmacopoeia) as an analgesic and antispasmodic ( Used for gastrointestinal). Anchusan is the main drug.

  Enmezo (prolonged herb) is a terrestrial part of the family Lamiaceae (Plectranthus japonicus Koidzumi) or Kurobanahikokushi (Plectranthus tricharpus Maximowicz (Labiatae)), and is mainly used for bitter and healthy stomach as a crude drug (Japanese Pharmacopoeia exogenous drug standard) used. In addition, antitumor effects, vasodilatory effects, bacterial growth inhibitory effects, and blood circulation promoting effects are known.

  Ougon is a root excluding the pericarp of Labiatae's Scutellaria baicalensis Georgi, and is mainly used as a crude drug (Japanese Pharmacopoeia) for stomachic medicine.

  Oubak (bark) is a bark excluding the pericarp of Pellodendoron amurense Ruprecht or other homologous plants (Rutaceae) of the citrus family (Rutaceae), and is mainly used as a crude drug (Japanese pharmacopoeia) for stomachic and antipruritic drugs. Used for applications.

  Spruce (cherry bark) is a bark excluding the cork skin (pereskin) of the wild cherry (Prusus jamasakura Sieboid of Rosaceae (Rosaceae) or other related plants (Rosaceae). Used for antitussive, expectorant, antidote for food poisoning, etc.

  Ouren is a rhizome excluding the roots of Coptis japonica Makino or other related plant (Ranunculaceae), and is mainly used for stomachic medicine and antipruritics as a crude drug (Japanese Pharmacopoeia). used.

  Onji is the root of the Polygalaceae Polygala tenuifolia Willdenow, and is mainly used as an expectorant as a crude drug (Japanese Pharmacopoeia).

  Gadju is a rhizome of Curcuma zedoaria Roscoe belonging to the genus Curcuma of Zingiberaceae, and is mainly used as a crude drug (Japanese Pharmacopoeia) for stomachic medicine. In addition, gadju is a plant name at the same time as a crude drug name (Japanese Pharmacopoeia).

  Licorice is a root and stron of Glycyrrhiza uralensis Fischer, Glycyrrhiza glabra Linne or other related plants of the leguminous family (Leguminosae) (sometimes excluding pericarp: peeled licorice), mainly as a crude drug (Japanese Pharmacopoeia) Used for analgesic antispasmodic drugs (gastrointestinal drugs) and expectorants.

  Kyokyo (Kikkyo) is the root of Platycodon grandiflorum A. DC. Belonging to Campanulaceae and Platycodon grandiflorum A. DC. It is mainly used as a herbal medicine (Japanese pharmacopoeia) for expectoration. The Kyoki is a herbal medicine (Japanese pharmacopoeia) and a plant name.

  A pheasant is a fruit of the Rutaceae daidai (Citrus aurantium L. var. Daidai Makino), a jujube (Citrus natsudaidai Hayata), or an immature fruit of a related plant, either as it is or cut in half. Yes, it is mainly used for stomachic medicine as a crude drug (Japanese Pharmacopoeia).

  Kyonin (Anjin) is a seed of Prunus armeniaca L., apricot (Prunus armeniaca L. var. Ansu Maximowicz) or other related plant of Rosaceae, and is mainly used as a crude drug (Japanese Pharmacopoeia). Used for expectorants.

  Kukosi is a fruit of Solanaceae's Lycium chinense Miller or Lycium barbarum L. It is mainly used as a herbal medicine (Japanese pharmacopoeia exogenous drug standard) for prosthetic kidney, live semen blood, and clear eye Is done.

  Keihi (Cinnamon) is a bark of the Cinnamomum cassia Blume of Lauraceae or other related genera, or part of the pericarp. It is mainly used as a crude drug (Japanese Pharmacopoeia) for stomachic medicine. Is done.

  Gentian is the root or rhizome of Gentianaceae's Gentianaceae (Gentiana lutea LINNE), and is mainly used as a herbal medicine (Japanese pharmacopoeia) for stomachic medicine. In addition, gentian is a plant name as well as a crude drug name (Japanese Pharmacopoeia).

  Gennoshouko is a perennial plant of Geraniaceae, an aerial part of Geranium thunbergii Sieb. Et Zucc., And is mainly used as a crude drug (Japanese Pharmacopoeia) for intestinal and antipruritic drugs. Genokosho is a herbal medicine name (Japanese Pharmacopoeia) and a plant name.

  Koujin (Red Ginseng) is dried from steamed roots of Panax Ginseng CA Meyer (Araliaceae) and is mainly used as a crude drug (Japanese Pharmacopoeia) for stomachic medicine and health tonic Is done.

  Koboku is a bark of Magnolia obovata Thunberg, Magnolia officinalis Rehder et Wilson or Magnolia officinalis Rehder et Wilson var. Biloba Rehder et Wilson (Magnoliaceae), a herbal medicine (Japanese Pharmacopoeia) Mainly used for stomachic medicine and analgesic / antispasmodic (gastrointestinal).

  Gomin is a fruit of Schisandra chinensis Baillon of Schisandraceae and is used as a crude drug (Japanese Pharmacopoeia). In addition to uses such as tonics, antioxidant and liver protecting effects are known.

  Psycho (Saiko) is the root of the Bupleurum falcatum L. or its variant (Umbelliferae) in the family Umbelliferae, and is used as a crude drug (Japanese Pharmacopoeia). In addition to its antipyretic action, it is used as the main agent of Sho-saiko-to and is used in “Saiko-ka-ryukotsu-oyster-to”, which is often prescribed for autonomic dysfunction.

  Saishin is a root and rhizome of Aristolochiaceae's Athasolocyaceae, Asiasarum sieboldi F. Maekawa or Keirinsaicin Asiasarum heterotropoides F. Maekawa var. Mandshuricum F. Maekawa, and is used as a crude drug (Japanese Pharmacopoeia). The Antipyretic action, antibacterial action, analgesic action, and sedative action are known.

  Sankirai is a tuber of the liliaceae, Sanilax glabra Roxburgh, and is used as a herbal medicine (Japanese Pharmacopoeia). Sankirai is not only a plant name but also a crude drug name (Japanese Pharmacopoeia).

  Hawthorn is a product of the Rosaceae hawthorn Crataegus cuneata Siebold et Zuccarini or the fruit crab Crataegus pinnatifida Bunge var. Major NE Brown. ) Is used to improve indigestion. Hawthorn is a herbal medicine name (Japanese Pharmacopoeia exogenous medicine regulation) and a plant name.

  Sanshishi is the fruit of Gardenia jasminoides Ellis or other related plants of the Rubiaceae family, and is used as a crude drug (Japanese Pharmacopoeia). It is formulated as an anti-inflammatory, hemostatic, antipyretic, and analgesic for diseases involving mental anxiety, hyperemia, vomiting, hematuria, melena, and jaundice.

  The salamander is the mature pericarp of the Rutaceae salamander Zanthoxylum piperitum De Candolle or other related genera, excluding seeds separated from the pericarp as much as possible. Used for medicinal purposes. Salamander is both a herbal medicine (Japanese Pharmacopoeia) and a plant name.

  Jiou (jio) is the root of Rehmannia glutinosa Liboschitz var. Purpurea Makino or Rehmannia glutinosa Liboschitz from Scrophulariaceae or steamed from it, and is used mainly as a health tonic as a crude drug (Japanese Pharmacopoeia) Is done.

  Peonies are the roots of Paeonia lactiflora Pallas from Paeoniaceae or other related plants, and are mainly analgesic antispasmodic drugs (gastrointestinal drugs), gynecological drugs, cold medicines, colds as crude drugs (Japanese Pharmacopoeia) Used for medicine and other purposes. Peonies are both herbal medicines (Japanese Pharmacopoeia) and plant names.

  Shazensou (Plant inaceae) is a whole plant of the plant of Plantago asiatica L. of Plantaginaceae and is mainly used for expectoration as a crude drug (Japanese Pharmacopoeia).

  Juyaku (ten drugs) is the flowering ground part of Houttuynia cordata Thunberg of Sauruaceae, and is mainly used as a herbal medicine (Japanese Pharmacopoeia) as a stool medicine or for diuresis / anti-inflammatory purposes in chronic skin diseases .

  Ginger is a rhizome of Zingiber officinale Roscoe from Zingiberaceae, and is mainly used as a crude drug (Japanese pharmacopoeia) for stomachic medicine.

  Senega is the root of Senega Polygala senega L. or Polygala senega L. var latifolia Torrer et Gray (Polygalaceae), and is mainly used as a herbal medicine (Japanese pharmacopoeia) for expectoration. In addition, Senega is a plant name as well as a crude drug name (Japanese Pharmacopoeia).

  Senkyu is a rhizome of Umbelliferae's nematode Cnidium officinale Makino, usually boiled and used as a herbal medicine (Japanese Pharmacopoeia) mainly for use in gynecological and cold medicines. Senkyu is a herbal medicine name (Japanese Pharmacopoeia) and a plant name.

  The assembly is the whole flower of the Gentianaceae assembly (Swertia japonica Makino) in the flowering period, and is mainly used as a herbal medicine (Japanese Pharmacopoeia) for bitter stomachic medicine and intestinal medicine. The assembly is a herbal medicine name (Japanese Pharmacopoeia) and a plant name.

  Sojutsu is a rhizome of Atractylodes lancea De Candolle or Atractylodes chinensis Koidzumi of Compositae and is mainly used as a crude drug (Japanese Pharmacopoeia) for stomachic medicine.

  Soyo is the leaf and branch tip of Labiatae perilla frutescens Britton var. Acuta Kudo or other related plants, and is mainly used as a crude drug (Japanese Pharmacopoeia) for stomachic medicine.

  Daioh is a common rhizome of Rheum palmatum L., Rheum tanguticum Maximowicz, Rheum officinale Baillon, Rheum coreanum Nakai or their interspecific hybrids (Polygonaceae), mainly as a herbal medicine (Japanese Pharmacopoeia) Used for stomachic and laxatives.

  Taisou is the fruit of the Rhamnaceae jujuba Zizyphus jujuba Miller var. Inermis Rehder or other related plants, and herbal medicines (Japanese Pharmacopoeia) include cold medicines, analgesic antispasmodic drugs, stomach digestive drugs, Used in combination with prescriptions such as hemorrhoids.

  Chimpi is a mature pericarp of the Rutaceae citrus unshiu Markovich or other related plants, and is mainly used as a crude drug (Japanese pharmacopoeia) for stomachic medicine.

  Toki (Toki) is usually boiled in the root of Angelica acutiloba Kitagawa or other related plants of the Umbelliferae family, and herbal medicine (Japanese Pharmacopoeia) includes gynecology, cold medicine, health tonic Used in prescriptions such as drugs, psychiatric and urinary tract diseases.

  Tocon is the root and rhizome of Cephaelis ipecacuanha (Broterol) A. Richard or Cephaelis acuminata Karsten (Rubiaceae) and is mainly used in expectorants as a crude drug (Japanese Pharmacopoeia).

  Nantenjitsu (Nami Tenji) is a fruit of the barberry family Nandina domestica Thumb. Var. Leucocar pa Makino or Nanten Nandina domestica Thumb., And is mainly used as an antitussive drug as a crude drug (Japanese Pharmacopoeia exogenous drug standard).

  Carrots are roots of Panax ginseng, Panax ginseng (Panax schinseng Nees) from the Araliaceae family, or lightly boiled, and are mainly used as health tonics and stomach medicines as crude drugs (Japanese Pharmacopoeia). Used for.

  Bakumondou is a huge part of the root of the Liiliaceae Ophiopogon japonicus Ker-Gawler or other related plants, and is mainly used in antitussive expectorant as a crude drug (Japanese Pharmacopoeia) .

  The peanut is a rhizome of Compositae's Okera Atractylodes japonica Koidzumi ex Kitamura or Ochana Okera Atractylodes ovata De Candolle, and is mainly used as a crude drug (Japanese Pharmacopoeia) for stomachic medicine.

  Button pi (peony skin) is the root bark of the button Paeonia suffruticosa Andrews (Paeonia moutan Sims) of the Paeoniaceae, and is mainly used in gynecological drugs as a crude drug (Japanese Pharmacopoeia).

  The hop is a vine perennial hop (Humulus lupulus Linn.) From Moraceae, and its premature female hops (Hops) have a bitter taste, diuresis, anti-insomnia, anti-neuroses since ancient times. It is used as a medicinal herb for sedation, menstruation, etc.

  Maou is the ground stem of Ephedra sinica Stapf of the family Ephedraceae or other related genera, and is mainly used for antitussive expectorant as a crude drug (Japanese pharmacopoeia).

  Mokko is the root of the compositae Saussurea lappa Clarke, and is mainly used as a crude drug (Japanese pharmacopoeia) for stomachic medicine.

  Yokuinin is a seed excluding the seed coat of Gramineae pearl barley Coix lacryma-jobi L. var. Ma-yuen Stapf, and it is used internally to improve warts and rough skin mainly as a crude drug (Japanese Pharmacopoeia). Used in medicine.

  Ryutan is the root and rhizome of Gentianaceae's Gentianaceae Gentiana scabra Bunge or other related plants, and is mainly used as a crude drug (Japanese Pharmacopoeia) for stomachic medicine.

  Rotcon is a rhizome and root of the scopolia japonica Maximowicz or other related plant (Solanaceae), and is mainly used for analgesics and antispasmodics as a crude drug (Japanese Pharmacopoeia).

  The plant extract used in the present invention uses the whole plant or a part thereof (for example, above-ground part, leaf, flower, stem, wood part, bark, bark part, root, rhizome, root bark, seed, etc.) as an extraction solvent. Can be obtained by extraction. Moreover, when a plant extract is derived from the above-mentioned plant crude drug, it can be obtained by extracting the crude drug with an extraction solvent. The plant (all or part) to be extracted may be (raw) or raw crushed or pulverized product, or may be crushed or pulverized as necessary after drying.

  Examples of the extraction solvent include water, an organic solvent, or a mixed solvent of water and an organic solvent (hydrous organic solvent). Water or a water-containing organic solvent is preferable.

  Here, the organic solvent is not particularly limited as long as it meets the above-mentioned purpose, and a lower aliphatic alcohol and a polar solvent can be widely used. More specifically, examples of the lower aliphatic alcohol include alcohols having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms such as methanol, ethanol, propanol and isopropyl alcohol and butanol; examples of polar solvents include acetone, ethyl acetate, Methyl acetate or the like is used. Preferred are lower aliphatic alcohols such as methanol, ethanol, propanol and isopropyl alcohol, and acetone, and more preferred is ethanol from the viewpoint that it can be applied orally to humans.

  In addition, these organic solvents may be used independently and can also be used in combination of 2 or more type. The mixing ratio of water and the organic solvent is not particularly limited and can be conventionally used.

  The extraction method is not limited, and a method generally used for plant extraction can be employed. Although it is not limited, for example, a method of immersing a plant (as it is, crushed or pulverized product or dried product thereof) by cold immersion, digestion, etc., a method of extracting with heating and stirring (heating reflux method) And a percolation method.

  After the extraction, the solid is separated by solid-liquid separation by a conventional method such as filtration or centrifugation. The obtained extract may be used as it is as the extract of the present invention, or may be concentrated or dried as necessary. Although the degree of concentration is not particularly limited, it is preferable to adjust the concentration so as to comply with pharmacopoeia standards or crude drug standards. For example, taking a peonies as an example, it is preferable to adjust so that the peoniflorin which is the specific component may be contained in the peonies extract in the ratio of 2% or more.

  The method of the present invention is a method for producing a plant extract-containing granule by extrusion granulation, wherein water, ethanol and menthol are used as a kneading liquid used in the kneading step. It is. Here, menthol is not particularly limited, and may be either l-form or d-form. L-menthol is preferable.

  Hereinafter, the method of the present invention will be described with reference to FIG. 1 showing a flowchart of a conventional extrusion granulation method. The method of the present invention is characterized in that water, ethanol and menthol are used as the kneading liquid used in the kneading step as described above, and as long as the other steps in the extrusion granulation method are used. And the specific operation is not limited at all. That is, FIG. 1 is only a diagram used for convenience of description of the present invention, and the method of the present invention is not limited to the extrusion granulation method described in FIG. 1 and widely applied to the extrusion granulation method. It can be done.

(1) “Preparation” and “Mixing” Steps The above-mentioned plant extract (corresponding to “drug” in FIG. 1) and other raw material components (corresponding to “other raw materials” in FIG. 1) are prepared to prepare a powder. And then mixing with a kneader for a predetermined time to prepare a mixed powder.

  In addition, as another raw material component used in combination with a plant extract here, the carrier and additive normally used for a pharmaceutical formulation can be mentioned. Also, other drugs can be added as long as they do not interfere with the effects of the plant extract to be added. In addition, it is preferable that the raw material component mix | blended here is prepared in the powder form.

  In this case, the content ratio of the plant extract in the above-mentioned compounded powder or mixed powder is not particularly limited, but usually the plant extract is in the range of 0.1 to 50 g, more preferably 1 to 100 g in the powdered compound or mixed powder. A range of 30 g, more preferably a range of 2 to 20 g can be mentioned. Although 1 g of plant extract varies depending on the type of raw material plant, it usually corresponds to 0.01 to 60 g, preferably 0.02 to 50 g, more preferably 2 to 40 g of the raw material plant.

  In this step, the preparation or mixing of the plant extract and other raw material components can be performed by adding water. In the water used at this time, a part of the kneading liquid described later can be used. The ratio of water used for blending or mixing is not particularly limited as long as it is less than the amount of water used as a kneading liquid described later. Usually, it can be used in the range of 50% or less, preferably 1 to 50% of the water used as the kneading liquid.

  Carriers and additives include corn starch, potato starch, sucrose, lactose, talc, kaolin, calcium sulfate, calcium carbonate, and crystalline cellulose; lubricants such as magnesium stearate and calcium stearate; carboxy Disintegrants such as methylcellulose calcium and low-substituted hydroxymethylcellulose: binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, cellulose polymer, acrylic polymer, methylcellulose, gum arabic, and polyvinyl alcohol; , Minerals, vitamins, amino acids, sweeteners, flavoring agents, coloring agents, flavoring agents, antioxidants, adsorbents, preservatives, wetting agents, and antistatic agents.

  Other drugs include, but are not limited to, central nervous stimulants, antihistamines / antiallergic drugs, parasympathetic blockers, sympathomimetic drugs (vasoconstrictors), anti-inflammatory enzymes, anti-inflammatory drugs, herbal medicines, antitussives, expectorants Examples include drugs, vaginal solubilizers, antipruritics, antipyretic analgesics, antacids, mucosal repair agents, intestinal preparations, gastric agents, digestives, analgesic antispasmodics, antipruritics and the like.

  Specifically, caffeine is exemplified as the central nervous stimulant, and specific examples include anhydrous caffeine, caffeine, sodium benzoate caffeine and the like. Antihistamines and antiallergic agents include isothipentyl hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, carbinoxamine, astemizole, clemastine fumarate, mequitazine, chlorpheniramine maleate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tanninate, diphenhydramine, Examples include amlexanox, cyproheptadine, ketotifen fumarate, alimemazine tartrate, tranilast, pemirolast potassium, azelastine hydrochloride, oxatomide, emedastine fumarate, epinastine hydrochloride, and salts thereof.

  Examples of parasympathetic nerve blockers include datsura extract, belladonna alkaloid, belladonna total alkaloid, belladonna extract, funnel extract, and isopropamide iodide. Sympathomimetic drugs include phenylpropanolamine hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, ephedrine hydrochloride, methoxyphenamine hydrochloride, norepinephrine, naphazoline nitrate, gyrometazoline, middolin, methoxamine, tetrahydrozoline, etc., or salts thereof It is done.

Antitussives include dextromethorphan hydrobromide, dextromethorphan, noscapine hydrochloride, noscapine, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, methoxyphenamine hydrochloride, and the like. Examples of expectorants include bromhexine hydrochloride and ambroxol hydrochloride. Examples of antipyretic analgesics include aspirin, aspirin aluminum, acetaminophen, etenzamide, salicylamide, ibuprofen, phenacetin, diclofenac sodium, pranoprofen and the like. Antacids include H ₂ receptor antagonists such as cimetidine, ranitidine, and famotidine; inorganic salts such as magnesium aluminate metasilicate, synthetic hydrotalcite, magnesium oxide, aluminum hydroxide, sodium bicarbonate, and calcium carbonate Etc.

  The above drugs are merely examples, and can be appropriately selected and adjusted within the scope of the object of the present invention.

(2) “Kneading” step This is a step of kneading the mixed powder obtained in the above (1) “preparation” and “mixing” steps. This kneading can be performed by adding a kneading liquid to the mixed powder prepared above and kneading (kneading) the mixture using a kneader or the like.

  Water, ethanol and menthol are used as the kneading liquid. In addition, the quantity of the water used as a kneading liquid can be selected from the range of 5-30 weight part with respect to 100 weight part of mixed powder. Preferably it is 10-18 weight part, More preferably, it is 12-16 weight part. A part of the water can also be used in the preparation or mixing step, which is a pre-step of the kneading step as described above.

  The amount of ethanol used as the kneading liquid can be determined based on the proportion of water used in the kneading liquid. Usually, 1-100 weight part can be mentioned as a ratio of ethanol with respect to 100 weight part of water. Preferably it is 5-50 weight part, More preferably, it is 10-30 weight part. The amount of menthol used as the kneading liquid can be determined based on the proportion of ethanol used in the kneading liquid. Usually, the ratio of menthol to 100 parts by weight of ethanol includes 1 to 50 parts by weight. Preferably it is 3-30 weight part, More preferably, it is 5-20 weight part.

  The kneading liquid may be used as a mixed liquid containing these three components, or may be used separately, or one component and two components may be used separately as the kneading liquid. Preferably, menthol is blended with ethanol and used as menthol-containing ethanol. That is, as the kneading liquid, it is desirable to use two kinds of water and ethanol containing menthol. In this case, the order of addition to the mixed powder is not particularly limited.

  The kneading step can be completed when the kneading liquid has spread throughout the mixed powder and becomes uniform.

(3) “Granulation” step In this step, the kneaded product obtained in the above-mentioned (2) “kneading” step is put in a granulator (granulator) and granulated (granulated). The granulation may be performed by an “extrusion granulation” mechanism, and the type of granulator (granulator) is not limited. For example, a so-called “extrusion granulator” that forcibly extrudes a kneaded material from a punching plate on a disk by rotating a screw also presses the kneaded material from a cylindrical punching plate by rotating an extrusion blade. Since all of the “granulators” of the dispensing system basically have a mechanism for extruding the kneaded material from the punching plate, they can be used as a granulator (granulator) in the present invention.

  The hole diameter of a punching board can be suitably selected according to the particle size of the granule to prepare. Usually, it can be selected from the range of 0.3 to 2 mm, preferably 0.5 to 1.5 mm.

  The granulation conditions employed in the “granulation” step can be appropriately selected and adjusted based on the common general technical knowledge in the industry.

(4) “Drying” step In this step, the raw granule obtained in the above-mentioned (3) “granulation” step is dried. Specifically, the drying step can be performed by a method of spreading the raw granule obtained in the above step on a plurality of trays and using a ventilation dryer or a method using a fluidized bed dryer. However, it is not limited to this method.

(5) “Granulation” and “Sieving” Step This is a step of adjusting the particle size of the dry granule obtained in the above (4) “drying” step. Specifically, the granulation step may be performed by regulating the dry granule obtained in the above step with a crusher such as a speed mill and collecting particles in a desired particle size range with a sieving machine. it can.

  The granules obtained in the above series of steps can be used as they are as preparations (powder, fine granules, granules, or dry syrup), or they are filled into a capsule base material to prepare hard capsules. Can be used as a “tablet granule” and as a core tablet for preparing a tablet (“tablet granule”). Furthermore, the above-mentioned granules can also be used as core particles (“granule for film formation”) of coated granules formed by coating with various coating agents including sugar.

  Therefore, the present invention provides a plant extract-containing granule prepared by the above method as a powder, granule, fine granule, dry syrup or the like itself, and a capsule formulation in which it is filled. Provided are tablets prepared through further steps using a plant extract-containing granule as a core tablet, and coated granules whose periphery is coated with various coating agents using a plant extract-containing granule as a core It is.

  Here, examples of the coating agent include gelatin, sugar (sucrose), and various films (water-soluble film, enteric film, sustained-release film) and the like. The coating granules formed by using sugar (sucrose), a water-soluble film, an enteric film, and a sustained-release film as a coating agent are sugar-coated granules, water-soluble granules, enteric granules, And called sustained release granules.

  In addition, the preparation method of a capsule formulation and the kind of capsule base material used for it, and the preparation method of a film granule and the kind of coating agent used for it can follow the technical common sense of those skilled in the art (for example, "development of pharmaceutical products "Volume 11" unit operation and machine of preparation, Yodogawa Shoten: "Pharmaceutical Development Vol.12" Formulation Material I, Yodogawa Shoten, pp. 198-227).

  In addition, a tablet having a plant extract-containing granule as a core tablet is, according to a conventional method, a mixed powder obtained by adding an excipient, a binder, a disintegrant and other additives to a plant extract and mixing them uniformly. After making into granules (granules) by the above method, it can be produced by adding a lubricant and compression molding (granule compression method, indirect compression method).

(2) Plant extract-containing granule The present invention also comprises a plant extract-containing granule containing the above-mentioned plant extract in a proportion of at least 2% by weight and having an appropriate water content of 0.5 to 10% by weight. provide.

  Here, as the plant extract, the above-mentioned Akamegashiwa, Fennel, Uyaku, Ages, Ezocogi, Engosac, Enmezou, Ogon, Ouaku, Ouhi, Ouren, Onji, Gajutsu, Licorice, Oyster, Pheasant, Kyonin, Kokushi, Keihi, Gentian, Gennoshouko, Kojin, Koboku, Gomin, Psycho, Saishin, Sankirai, Hawthorn, Sanshishi, Salamander, Giant, Peonies, Shazenso, Juyaku, Shoyo, Senega, Senkyu, Senburi, Suzutsu, Soyo, Daio, Taiso, Chichi, Toki Name extracts of herbal medicines such as Tokon, Nantenjitsu, Carrot, Bacmond, Sandalwood, Buttonpi, Hops, Maoh, Mokko, Yokuinin, Ryutan, or Rotokon It can be. Here, as the plant extract, one kind of plant extract may be used alone, or two or more plant extracts may be used in combination.

  The plant extract-containing granule contains 2% by weight or more of the plant extract as described above, preferably 2 to 20% by weight, more preferably 4 to 18% by weight, and still more preferably 6 to 16% by weight. % Is desirable. In addition, although 1g of plant extracts differ also with the kind of raw material plant, it is 0.01-60g normally, Preferably it is 0.02-50g, More preferably, it corresponds to 2-40g.

  The appropriate water content of the plant extract-containing granule means the amount of water and crystal water adhering to the granule, and can be specifically measured by the Karl Fischer method prescribed by the Japanese Pharmacopoeia. . As described above, the plant extract-containing granule of the present invention has an appropriate water content in the range of 0.5 to 10% by weight, preferably 1 to 8% by weight, more preferably 1.5 to 1.5%. It is in the range of 6% by weight. The appropriate amount of water is 0.025 to 5 parts by weight, preferably 0.05 to 2 parts by weight, and more preferably 0.05 parts by weight when converted to a ratio with respect to 1 part by weight of the plant extract contained in the plant extract-containing granule. It is desirable to be in the range of 1 to 1 part by weight.

  As long as said plant extract containing granule has the said composition, the carrier and additive normally used for a pharmaceutical formulation other than a plant extract may be mix | blended. In addition, other drugs can be included as long as they do not interfere with the effect of the plant extract to be blended. As specific carriers and additives, and other drugs, those described above can be used similarly.

  The plant extract-containing granule of the present invention is not particularly limited in its production method as long as it is a method capable of preparing the above composition. For example, it may be obtained by the extrusion granulation method described above in (1) or may be obtained by another granulation method. The granulation method can be roughly divided into wet granulation method and dry granulation method, but preferably wet granulation method (for example, extrusion granulation method, fluidized bed granulation method, stirring granulation method etc. are included) Can be mentioned. In this case, the kneading liquid used for kneading the mixed powder containing the plant extract is not limited, but it is desirable to use the kneading liquid described above, that is, a kneading liquid composed of water, ethanol and menthol. When using this kneading liquid, each component can be used in the ratio mentioned above.

  In addition, the present invention provides a plant having an appropriate water content of 0.5 to 10% by weight, which is prepared using a mixed powder containing a plant extract in a proportion of at least 2% by weight, water, ethanol, and menthol as raw materials. An extract-containing granule is provided.

  Examples of such plant extracts include the above-described extracts of plant herbal medicines, but peony extracts are preferred.

  Here, the mixed powder can include carriers and additives usually used in pharmaceutical preparations in addition to the above plant extract. Moreover, another drug can be mix | blended as long as it does not prevent the effect of the plant extract to mix | blend. For specific carriers and additives, and other drugs, those described above in (1) can be used as well. The proportion of the plant extract contained in the mixed powder may be at least 2% by weight as described above, but is preferably 2 to 20% by weight, more preferably 4 to 18% by weight, and further preferably 6 to 16%. % By weight. As described above, 1 g of the plant extract corresponds to 0.01 to 60 g, preferably 0.02 to 50 g, more preferably 2 to 40 g of a normal plant.

  Although it does not restrict | limit especially as a ratio of the water used for preparation, It can select from the range of 5-30 weight part with respect to 100 weight part of the said mixed powder. Preferably it is 10-18 weight part, More preferably, it is 12-16 weight part. The amount of ethanol used is not particularly limited, but can be 1 to 100 parts by weight with respect to 100 parts by weight of water. Preferably it is 5-50 weight part, More preferably, it is 10-30 weight part. Furthermore, although the usage-amount of menthol is not restrict | limited, 1-50 weight part can be mentioned with respect to 100 weight part of said ethanol usage-amounts. Preferably it is 3-30 weight part, More preferably, it is 5-20 weight part.

  The plant extract-containing granule of the present invention may finally have an appropriate water content in the range of 0.5 to 10% by weight. Preferably it is 1 to 8 weight%, More preferably, it is 1.5 to 6 weight%.

  Even if the plant extract-containing granule of the present invention described above is used as it is as a preparation (powder, fine granule, granule, or dry syrup), it is filled into a capsule base material to form a hard capsule. It may be used as a “capsule granule” for preparation or as a core tablet (“tablet granule”) for preparing a tablet. Further, the above granule may be used as a core particle (“granule for film formation”) of a film granule coated with various coating agents including sugar.

  Therefore, the present invention provides a plant extract-containing granule prepared by the above method as a powder, granule, fine granule, dry syrup or the like itself, and a capsule formulation in which it is filled. Provided are tablets prepared through further steps using a plant extract-containing granule as a core tablet, and coated granules whose periphery is coated with various coating agents using a plant extract-containing granule as a core It is.

  According to the extrusion granulation method of the present invention in which kneading is performed using three components of water, ethanol and menthol as a kneading liquid, even when a viscous plant extract is contained as a raw material, it is usually kneaded. It is possible to suppress the thickening over time of the mixed powder that occurs at the time of granulation or granulation (granulation), and as a result, continuously and stably preparing a granule having a desired particle size Can do.

  Hereinafter, the present invention will be described with reference to test examples and examples, but the present invention is not limited to these examples.

Test example 1
Granules having the following formulation were prepared by extrusion granulation according to the flowchart shown in FIG. In addition, as the following peonies extract, a soft extract obtained by extracting a dry cut of peonies (shape root) with water and concentrating the extract (1 g of peonies extract is peonies (root)) Equivalent to 4 g) was used.
<Prescription>
Peonies extract 0.325 kg (6.5%)
Magnesium aluminate metasilicate 1.000 (20.0%)
Lactose 3.675 (73.5%)
Total 5.000 kg (100.0%).

  Specifically, first, water (equivalent to “water (pre-addition)” in Table 1) was added in advance to 0.325 kg of peony extract (1.3 kg in terms of dried peony (root)) to form an aqueous solution. This was dropped into 1 kg of magnesium aluminate metasilicate (powder) and mixed for 15 seconds using a vertical granulator (manufactured by Paulette Co., Ltd.). Next, 3.675 kg of lactose (powder) was added thereto, and further mixed for 1 minute using a vertical granulator (manufactured by Paulette Co., Ltd.). A kneading liquid having a formulation described in Table 1 was dropped into the obtained mixed powder. In addition, about the test bodies 4 and 5, water and ethanol were dripped separately, and the menthol was previously mixed with ethanol and used as the menthol containing ethanol about the test body 5.

  This was further kneaded for 1 minute using a vertical granulator (manufactured by Paulette Co., Ltd.) (“kneading”). Next, the obtained kneaded product was transferred to a basket granulator (manufactured by Kikusui Seisakusho Co., Ltd.) equipped with a punching plate having a hole diameter of 1 mm and granulated (hereinafter, “granulation”). The obtained raw granules were dried with a fluid bed dryer (“drying” step), and the obtained dried granules were sieved with a sieve to obtain granules.

  In addition, the kneading degree in the kneading step shown in FIG. 2, the particle size after drying, and the temporary specific gravity, the yield, and the powdering rate after sieving were determined according to the following methods, respectively.

・Kneading degree :
100 g of the kneaded mass is placed on a 840 μm sieve and tapped 40 times by hand, and the remaining amount (xg) is calculated as a percentage (x%).

・Granularity :
20 g of the dried granule, 12 [1400 μm], 18 [850 μm], 30 [500 μm], 42 [355 μm], 60 [250 μm], 83 [180 μm], 100 [150 μm], 140 [140] 106 μm] sieves (each sieve diameter 75 mm) and receivers are placed in the top sieve of the apparatus and sieved for 5 minutes on a shaker to measure the amount (g) of dry granules remaining on each sieve. Divide the total amount of dry granules (g) remaining on the No. 30 [500 μm] and No. 42 [355 μm] sieves by the total amount of dry granules (about 20 g) remaining in each sieve and receiver, and calculate the percentage. Evaluate according to criteria.
◎: 75% to 100%, ○: 50% to less than 75%, △: 25% to less than 50%,
X: 0% or more and less than 25%.

・Provisional specific gravity :
The dry granules remaining on the No. 30 [500 μm] sieve by the above particle size measurement are placed in a 100 mL container, the amount (weight and volume) is measured, and the specific gravity (g / mL) is calculated.

・Yield :
Put all the dried granules produced into No. 18 [850μm], No. 30 [500μm], No. 42 [355μm] sieves (each sieve diameter 30cm) and receiver on the upper sieve, and shake with a shaker. Sift for 5 minutes to determine the amount (g) of dry granules remaining on each sieve. Divide the total amount (kg) of dry granules remaining on the No. 30 [500 μm] and No. 42 [355 μm] sieves by the weight of the raw material (kg) to calculate the percentage.

・Powdering rate
After 100 g of dry granules remaining on the No. 30 [500 μm] sieve are worn by rotating for 10 minutes with a rotary strength tester, the amount remaining on the 500 μm sieve is determined and displayed as a percentage.

  Furthermore, according to the following reference | standard, granulation property was evaluated about each test body.

・Granulation property ○: The granulator does not stop halfway.

Δ: Initial granulation was possible, but the granulator stopped halfway. ×: No granulation was possible.

  The results are shown in Table 1.

試験例２
表２の処方からなる顆粒剤を、試験例１と同様に、図２に示すフローチャートに従って押出し造粒法により作成した。そして、試験例１と同様にして、各試験体の造粒性を評価し、また粒度（％）と得率（％）を求めた。結果を表３に合わせて示す。

Test example 2
Granules having the formulation shown in Table 2 were prepared by extrusion granulation according to the flowchart shown in FIG. And it carried out similarly to Test Example 1, evaluated the granulation property of each test body, and calculated | required the particle size (%) and the yield (%). The results are shown in Table 3.

以上、試験例１と試験例２の結果から、練合液として、水に加えて、l-メントールとエタノールの混合液を用いることによって、練合時や製粒時の増粘が抑制でき、所望の粒度を有する顆粒が製造できることがわかった。

As described above, from the results of Test Example 1 and Test Example 2, in addition to water as a kneading liquid, by using a mixed liquid of l-menthol and ethanol, thickening at the time of kneading and granulation can be suppressed. It has been found that granules having the desired particle size can be produced.

Formulation Example 1 Cold Medicine (Fine Granules) Daily Amount (g)
Methylephedrine hydrochloride 0.6
Chlorpheniramine maleate 0.0075
Noscapine 0.048
Acetaminophen 0.45
Ethenzamid 0.75
Caffeine 0.075
Licorice extract 0.4 (1.6 g in terms of active ingredient)
Kyokyo Extract 0.2 (0.8g in terms of active ingredient)
Lactose residue
Total 5.0 g.

Formulation Example 2 Gastrointestinal (powder) daily dose (g)
Sodium bicarbonate 2.0
Magnesium oxide 0.6
Assembly extract 0.3 (1.2 g of raw drug equivalent)
Gentian extract 0.3 (1.5g in terms of active ingredient)
Lactose residue
Total 4.0 g.

It is a figure which shows the flowchart of the conventional extrusion granulation method. It is a figure which shows the flowchart of the extrusion granulation method used by the test example of this invention.

Claims (7)

A method for producing a plant extract-containing granule comprising a step of granulating by extrusion granulation after adding water, ethanol and menthol as a kneading liquid to a mixed powder containing a plant extract and kneading. Nerigoeki as, water, and menthol containing claim 1 method for producing a plant extract-containing granules according to, characterized by using the ethanol. The plant extract is Akamegashiwa, Fennel, Uyaku, Ages, Ezoukogi, Engosaku, Enmeiso, Ogon, Ouaku, Spruce, Ouren, Onji, Ganju, Licorice, Oyster, Pheasant, Kyonin, Kokushi, Keihi, Gentiana, Genko , Gomin, Psycho, Sankirai, Hawthorn, Saishin, Sanshishi, Salamander, Elephant, Peonies, Shazenso, Zyuyaku, Shoyo, Senega, Senkyu, Assembly, Sojitsu, Soyo, Daio, Taiso, Chimp, Toki, Tokon, Nantenjitsu, Carrot An extract of at least one herbal medicine selected from the group consisting of: Bacmondow, Sandalwood, Buttonpi, Hop, Maou, Mokko, Yokuinin, Ryutan and Rotokon The method of plant extract-containing granules according to claim 1 or 2. The method for producing a crude drug / plant extract-containing granule according to claim 1 or 2, wherein the plant extract is an extract of peony. The manufacturing method of the hard capsule which has the process of filling a capsule base material with the plant extract containing granule obtained by the granulation process in addition to the granulation process in any one of Claims 1 thru | or 4. The manufacturing method of the coated granule which has the process of coat | covering the plant extract containing granule obtained by the granulation process with a coating agent in addition to the granulation process in any one of Claims 1 thru | or 4. In addition to the granulation process described in any one of Claims 1 thru | or 4, the manufacturing method of the tablet which has the process of adding a lubricant to the plant extract containing granule obtained at the granulation process, and compression-molding.

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