Solid pharmaceutical composition

Abstract

To provide a solid preparation of Reitakutsukitokashini extract with suppressed discoloration.SOLUTION: A solid pharmaceutical composition comprising (A) Reitakutsukitokashini extract and (B) a predetermined compound selected from the group consisting of (B1) a cellulose compound, (B2) a stearate, and (B3) a silicate compound exhibits suppressed discoloration.SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to a solid pharmaceutical composition having excellent discoloration inhibitory properties.

Background Art

[0002] Reitaku Tsuki Kito plus Xin Yi is a Chinese herbal medicine based on "Wanbing Huichun" and is applicable to the following various symptoms in persons of moderate physical strength: olfactory disorder, olfactory abnormality, nasal congestion, allergic rhinitis, chronic rhinitis, and empyema (sinusitis). Non-Patent Document 1 reports a case where Reitaku Tsuki Kito plus Xin Yi was applied to sinusitis, and it is described that Reitaku Tsuki Kito plus Xin Yi using as the constituent crude drugs Ougi, Soushutsu, Kyoukatsu, Dokkatsu, Bofu, Shouma, Kakkon, Kanzou, Sanshou, Maoou, Byakushi, Shoukyou, Taisou, and Shin Yi was used.

[0003] On the other hand, generally, a solid pharmaceutical preparation containing a Chinese herbal extract requires a formulation design considering the hygroscopicity of the Chinese herbal extract in order to satisfy a predetermined formulation stability. For example, Patent Document 1 discloses a formulation in which an aqueous solution obtained by adding 1 / 20 to 1 / 2 part by weight of gelatin to a Chinese herbal extract is spray-dried to obtain a powder for preventing moisture absorption.

[0004] Furthermore, when the Chinese herbal extract formulated in a solid pharmaceutical preparation causes significant discoloration due to hygroscopicity, a more stringent formulation design is required to suppress discoloration. For example, Patent Document 2 discloses a formulation in which polyvinyl acetate is blended with a Chinese herbal extract.

Prior Art Documents

Non-Patent Documents

[0005]

Non-Patent Document 1

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0007] When the present inventor tested the formulation stability of Lizawa Tongqi Decoction plus Magnolia Flower Extract, a problem of significant discoloration occurred. Therefore, an object of the present invention is to provide a solid preparation of Lizawa Tongqi Decoction plus Magnolia Flower Extract with suppressed discoloration.

Means for Solving the Problems

[0008] As a result of intensive studies, the present inventors have found that discoloration can be suppressed by blending a predetermined compound selected from the group consisting of a cellulose compound, a stearate, and a silicate compound into Lizawa Tongqi Decoction plus Magnolia Flower Extract. The present invention has been completed by further studies based on this finding.

[0009] That is, the present disclosure provides an invention in the following aspects. Item 1. A solid pharmaceutical composition comprising (A) Lizawa Tongqi Decoction plus Magnolia Flower Extract, and (B) a predetermined compound selected from the group consisting of (B1) a cellulose compound, (B2) a stearate, and (B3) a silicate compound. Item 2. The solid pharmaceutical composition according to Item 1, wherein the component (B1) is selected from the group consisting of cellulose, crystalline cellulose, calcium carmellose, croscarmellose calcium, and hydroxypropyl cellulose. Item 3. The solid pharmaceutical composition according to Item 1 or 2, wherein the component (B3) is selected from the group consisting of silicon dioxide, aluminum silicate, magnesium aluminometasilicate, and talc. Item 4. The solid pharmaceutical composition according to any one of Items 1 to 3, wherein the content of the component (B) per 100 parts by weight of the component (A) is 0.05 to 70 parts by weight in total. Item 5. The solid pharmaceutical composition according to any one of Items 1 to 4, wherein the content of the component (A) is 50 to 95% by weight. Item 6. The solid pharmaceutical composition according to any one of Items 1 to 5, wherein the content of the component (B) is 0.05 to 50% by weight in total. Item 7. The solid pharmaceutical composition according to any one of Items 1 to 6, further comprising (C) starch and / or lactose.

Effects of the Invention

[0010] According to the solid pharmaceutical composition of the present disclosure, a solid preparation of Lize Tongqi Decoction plus Magnolia Flower Extract with suppressed discoloration can be provided.

Modes for Carrying Out the Invention

[0011] 1. Solid pharmaceutical composition The solid pharmaceutical composition of the present disclosure comprises (A) Lize Tongqi Decoction plus Magnolia Flower Extract (hereinafter also referred to as the “component (A)”), and (B) a predetermined compound selected from the group consisting of (B1) a cellulose compound (hereinafter also referred to as the “component (B1)”), (B2) a stearate (hereinafter also referred to as the “component (B2)”), and (B3) a silicate compound (hereinafter also referred to as the “component (B3)”) (hereinafter, the components (B1) to (B3) are collectively also referred to as the “component (B)”). Hereinafter, the solid pharmaceutical composition of the present disclosure will be described in detail. In this specification, a numerical range indicated by two numerical values and “~” shall include those two numerical values as the lower limit value and the upper limit value. For example, the notation of 2 to 15% by weight means 2% by weight or more and 15% by weight or less.

[0012] (A) Lizetongqi Decoction plus Flos Magnoliae Extract The solid pharmaceutical composition of the present disclosure contains Lize Tongqi Decoction plus Magnolia Flower Extract as component (A). The crude drugs constituting Lize Tongqi Decoction plus Magnolia Flower are Angelica dahurica, Zanthoxylum schinifolium, Bupleurum falcatum, Ephedra sinica, Pueraria lobata, Paeonia lactiflora, Cnidium officinale, Zingiber officinale, Bupleurum chinense, Glycyrrhiza uralensis, Asarum sieboldii, and Magnolia biondii (Saposhnikovia divaricata may be further added. Preferably, it does not contain Saposhnikovia divaricata.). The crude drug preparation used for the production of Lize Tongqi Decoction plus Magnolia Flower Extract consists of Angelica dahurica, Zanthoxylum schinifolium, Bupleurum falcatum, Ephedra sinica, Pueraria lobata, Paeonia lactiflora, Cnidium officinale, Zingiber officinale, Bupleurum chinense, Glycyrrhiza uralensis, Asarum sieboldii, and Magnolia biondii (Saposhnikovia divaricata may be further added. Preferably, it does not contain Saposhnikovia divaricata.). Preferred examples of the amounts of these crude drugs are 2 to 4 parts by weight of Angelica dahurica, 0.5 to 1 part by weight of Zanthoxylum schinifolium, 1.5 to 3 parts by weight of Bupleurum falcatum, 0.5 to 1 part by weight of Ephedra sinica, 1.5 to 3 parts by weight of Pueraria lobata, 2 to 4 parts by weight of Paeonia lactiflora, 1.5 to 3 parts by weight of Cnidium officinale, 0.5 to 1 part by weight of Zingiber officinale, 1.5 to 3 parts by weight of Bupleurum chinense, 0.5 to 1 part by weight of Glycyrrhiza uralensis, 0.5 to 1 part by weight of Asarum sieboldii, and 1.5 to 3 parts by weight of Magnolia biondii.

[0013] The Lize Tongqi Decoction plus Magnolia Flower Extract used in the present disclosure can be obtained by extracting the above crude drug preparation by a known method. Although the extraction solvent used in the extraction treatment is not particularly limited, examples include water or aqueous ethanol, and preferably water. Regarding the method for extracting the above crude drug preparation, for example, about 10 to 20 times the amount, preferably 10 to 15 times the amount of the extraction solvent is added to the crude drug preparation, and it is stirred and extracted at about 80 to 100°C, preferably 95 to 100°C for about 20 minutes to 3 hours, preferably 30 minutes to 1 hour. After extraction, it is subjected to solid-liquid separation such as centrifugation and filtration to remove solids, and then subjected to a drying treatment to obtain Lize Tongqi Decoction plus Magnolia Flower Extract powder.

[0014] Although the specific method of the drying treatment is not particularly limited, the extract from which the solid content has been removed may be concentrated as necessary and then subjected to a drying treatment such as spray drying, vacuum concentration drying, freeze drying, or the like. Further, when subjecting to the drying treatment (particularly, the drying treatment by spray drying), an excipient may be added to the extract as necessary.

[0015] The content of the component (A) in the solid pharmaceutical composition of the present disclosure (which refers to the amount in terms of dry extract; the same applies hereinafter) is not particularly limited, and examples thereof include 50 to 95% by weight, preferably 52 to 80% by weight, more preferably 55 to 75% by weight, and still more preferably 60 to 70% by weight.

[0016] Note that the amount in terms of dry extract is the amount itself when dry extract (extract powder) is used, and when an extract solution or soft extract is used, it is the amount converted to the remaining amount after removing the solvent. Further, when the dry extract powder contains additives such as excipients added during production, it is the amount excluding the additive.

[0017] (B) Predetermined compound The solid pharmaceutical composition of the present disclosure contains, as the component (B), a predetermined compound selected from the group consisting of (B1) a cellulose compound, (B2) a stearate, and (B3) a silicate compound. The component (B) suppresses discoloration during storage in the solid pharmaceutical composition containing the component (A). In the present disclosure, as the component (B), the component (B1) or the component (B2) may be used alone, or the component (B1) and the component (B2) may be used in combination.

[0018] In the present disclosure, the cellulose compound as the component (B1) refers to cellulose, a partial depolymerization product of cellulose, or a cellulose derivative. Examples of the partial depolymerization product of cellulose include crystalline cellulose. A cellulose derivative is a compound in which a functional group is introduced via a hydroxyl group of cellulose. Specifically, examples include cellulose ethers in which a functional group is introduced by an ether bond and cellulose esters in which a functional group is introduced by an ester bond. Among these, from the viewpoint of improving the discoloration suppression effect, cellulose ethers are preferably mentioned. Examples of cellulose ethers include carmellose (i.e., carboxymethyl cellulose), carmellose salts (more specifically, alkali metal salts of carmellose and alkaline earth metal salts of carmellose), crosscarmellose salts (i.e., crosslinked carmellose salts; more specifically, alkali metal salts of crosscarmellose, alkaline earth metal salts of crosscarmellose), hydroxypropyl cellulose, and the like.

[0019] These components (B1) may be used alone or in combination of two or more. Among these components (B1), from the viewpoint of enhancing the discoloration suppression effect, preferably, carmellose salts, cellulose, crosscarmellose salts, hydroxypropyl cellulose, and crystalline cellulose are mentioned; more preferably, carmellose salts, cellulose, crosscarmellose salts, and hydroxypropyl cellulose are mentioned; still more preferably, carmellose salts, cellulose, crosscarmellose salts (preferably, alkali metal salts of crosscarmellose, alkaline earth metal salts of crosscarmellose, more preferably, alkali metal salts of crosscarmellose, still more preferably, sodium crosscarmellose) are mentioned; even more preferably, crosscarmellose salts and cellulose are mentioned; particularly preferably, crosscarmellose salts (preferably, alkali metal salts of carmellose, alkaline earth metal salts of carmellose, more preferably, alkaline earth metal salts of carmellose, still more preferably calcium carmellose) are mentioned.

[0020] Specific examples of the stearate which is the (B2) component include magnesium stearate, calcium stearate, barium stearate, and zinc stearate.

[0021] These (B2) components may be used individually or in combination of two or more. Among these (B2) components, magnesium stearate is preferably used from the viewpoint of improving the discoloration suppressing effect.

[0022] In the present disclosure, the silicic acid compound which is the (B3) component refers to silicon dioxide or silicate. Examples of the silicon dioxide include light anhydrous silicic acid and hydrous silicon dioxide. Examples of the silicate include aluminum silicate, magnesium aluminometasilicate, and talc.

[0023] These (B3) components may be used individually or in combination of two or more. Among these (B3) components, talc and magnesium aluminometasilicate are preferably used from the viewpoint of efficiently obtaining the discoloration suppressing effect; more preferably, talc is used. Further, when selecting hydrous silicon dioxide, aluminum silicate, and / or light anhydrous silicic acid as the (B3) component, among these, hydrous silicon dioxide and aluminum silicate are preferably used from the viewpoint of efficiently obtaining the discoloration suppressing effect with a smaller amount; more preferably, hydrous silicon dioxide is used.

[0024] The content of the (B) component in the solid pharmaceutical composition of the present disclosure is not particularly limited as long as the effects of the present disclosure are exhibited, but the ratio of the content per 100 parts by weight of the (A) component is 0.05 to 70 parts by weight in total.

[0025] (B1) component content is as follows. As the ratio of the content per 100 parts by weight of component (A), the total amount is 0.1 to 70 parts by weight, 0.5 to 70 parts by weight, 1 to 70 parts by weight, 5 to 70 parts by weight, 7 to 70 parts by weight, 10 to 70 parts by weight, 13 to 70 parts by weight, 14 to 70 parts by weight, 15 to 70 parts by weight, 18 to 70 parts by weight, 19 to 70 parts by weight, 20 to 70 parts by weight, 24 to 70 parts by weight, 25 to 70 parts by weight, 26 to 70 parts by weight, 28 to 70 parts by weight, 0.1 to 60 parts by weight, 0.1 to 55 parts by weight, 0.1 to 50 parts by weight, 0.1 to 45 parts by weight, 0.1 to 40 parts by weight, 0.1 to 36 parts by weight, 0.1 to 35 parts by weight, 0.1 to 34 parts by weight, 0.1 to 33 parts by weight, 0.1 to 30 parts by weight, 0.1 to 25 parts by weight, 0.1 to 24 parts by weight, 0.1 to 23 parts by weight, 0.1 to 18 parts by weight, or 0.1 to 16 parts by weight.

[0026] More preferably, according to the type of component (B1), the following contents can be selected as the ratio of the content per 100 parts by weight of component (A). · In the case of carmellose salt: 0.1 to 70 parts by weight, or 1 to 60 parts by weight, more preferably 5 to 50 parts by weight, or 15 to 40 parts by weight, still more preferably 25 to 36 parts by weight, or 28 to 34 parts by weight · In the case of cellulose: 1 to 70 parts by weight, or 5 to 50 parts by weight, more preferably 10 to 45 parts by weight, or 15 to 40 parts by weight, still more preferably 24 to 35 parts by weight, or 26 to 33 parts by weight · In the case of crosscarmellose salt: 1 to 55 parts by weight, or 5 to 45 parts by weight, more preferably 13 to 35 parts by weight, still more preferably 19 to 25 parts by weight, or 20 to 24 parts by weight · In the case of hydroxypropyl cellulose: 0.5 to 40 parts by weight, or 1 to 30 parts by weight, more preferably 7 to 25 parts by weight, or 10 to 23 parts by weight, still more preferably 13 to 18 parts by weight, or 14 to 16 parts by weight · In the case of crystalline cellulose: 5 to 60 parts by weight, or 7 to 55 parts by weight, more preferably 13 to 50 parts by weight, or 18 to 40 parts by weight, still more preferably 24 to 36 parts by weight, or 26 to 34 parts by weight

[0027] Regarding the content of component (B2), as the ratio of the content per 100 parts by weight of component (A), for example, it is 0.2 to 5 parts by weight, or 0.4 to 4.5 parts by weight, 0.6 to 4 parts by weight, preferably 0.75 to 3.5 parts by weight, 0.8 to 3.2 parts by weight, or 1 to 2.5 parts by weight, more preferably 1.3 to 2 parts by weight, 1.3 to 1.8 parts by weight, 1.3 to 1.7 parts by weight, or 1.4 to 1.6 parts by weight.

[0028] Regarding the content of component (B3), as the ratio of the content per 100 parts by weight of component (A), for example, it is 0.05 to 55 parts by weight, 0.1 to 55 parts by weight, 0.12 to 55 parts by weight, 0.14 to 55 parts by weight, 0.15 to 55 parts by weight, 0.2 to 55 parts by weight, 0.28 to 55 parts by weight, 0.3 to 55 parts by weight, 0.35 to 55 parts by weight, 0.5 to 55 parts by weight, 0.6 to 55 parts by weight, 0.9 to 55 parts by weight, 1 to 55 parts by weight, 1.2 to 55 parts by weight, 1.3 to 55 parts by weight, 1.4 to 55 parts by weight, 3 to 55 parts by weight, 4 to 55 parts by weight, 5 to 55 parts by weight, 5.5 to 55 parts by weight, 6 to 55 parts by weight, 6.5 to 55 parts by weight, 7 to 55 parts by weight, 10 to 55 parts by weight, 13 to 55 parts by weight, 14 to 55 parts by weight, 20 to 55 parts by weight, 26 to 55 parts by weight, 32 to 55 parts by weight, 35 to 55 parts by weight, 0.05 to 55 parts by weight, 0.05 to 52 parts by weight, 0.05 to 50 parts by weight, 0.05 to 46 parts by weight, 0.05 to 40 parts by weight, 0.05 to 35 parts by weight, 0.05 to 32 parts by weight, 0.05 to 30 parts by weight, 0.05 to 26 parts by weight, 0.05 to 25 parts by weight, 0.05 to 24 parts by weight, 0.05 to 20 parts by weight, 0.05 to 17 parts by weight, 0.05 to 16 parts by weight, 0.05 to 15 parts by weight, 0.05 to 13 parts by weight, 0.05 to 12 parts by weight, 0.05 to 10 parts by weight, 0.05 to 9.5 parts by weight, 0.05 to 9 parts by weight, 0.05 to 8.5 parts by weight, 0.05 to 8 parts by weight, 0.05 to 6 parts by weight, 0.05 to 5 parts by weight, 0.05 to 4 parts by weight, 0.05 to 3 parts by weight, 0.05 to 2.5 parts by weight, 0.05 to 2 parts by weight, 0.05 to 1.5 parts by weight, 0.05 to 1.3 parts by weight, 0.05 to 0.9 parts by weight, 0.05 to 0.85 parts by weight, or 0.05 to 0.8 parts by weight.

[0029] More preferably, depending on the type of component (B3), the following content can be selected as the content ratio per 100 parts by weight of component (A). · In the case of talc: 0.05 to 10 parts by weight, or 0.1 to 5 parts by weight, more preferably 0.1 to 3 parts by weight, 0.12 to 2 parts by weight, 0.14 to 1.5 parts by weight, or 0.2 to 1.3 parts by weight, still more preferably 0.28 to 0.9 parts by weight, 0.3 to 0.85 parts by weight, or 0.35 to 0.8 parts by weight · In the case of magnesium aluminometasilicate: 0.15 to 40 parts by weight, 0.15 to 30 parts by weight, or 0.6 to 25 parts by weight, more preferably 0.9 to 20 parts by weight, 1.2 to 17 parts by weight, or 1.2 to 13 parts by weight, still more preferably 1.2 to 10 parts by weight, 1.3 to 8.5 parts by weight, or 1.3 to 6 parts by weight, even more preferably 1.3 to 4 parts by weight, 1.4 to 3 parts by weight, 1.4 to 2.5 parts by weight, or 1.4 to 2 parts by weight · In the case of hydrous silicon dioxide: 0.5 to 35 parts by weight, 1 to 32 parts by weight, 1.2 to 30 parts by weight, 1.3 to 25 parts by weight, 1.4 to 20 parts by weight, 1.4 to 15 parts by weight, or 1.4 to 12 parts by weight, more preferably 1.4 to 10 parts by weight, 3 to 10 parts by weight, or 4 to 10 parts by weight, still more preferably 5 to 10 parts by weight, 5.5 to 9.5 parts by weight, 6 to 9 parts by weight, 6.5 to 8.5 parts by weight, or 7 to 8 parts by weight · In the case of aluminum silicate: 5 to 30 parts by weight, 6 to 26 parts by weight, 7 to 24 parts by weight, or 10 to 20 parts by weight, more preferably 14 to 18 parts by weight, or 15 to 17 parts by weight · In the case of light anhydrous silicic acid: 13 to 55 parts by weight, more preferably 20 to 52 parts by weight, or 26 to 52 parts by weight, still more preferably 32 to 50 parts by weight, or 35 to 46 parts by weight

[0030] The specific content of component (B) in the solid pharmaceutical composition of the present disclosure is determined according to the content of component (A) and the content ratio of component (B) per 100 parts by weight of component (A) described above, and preferably ranges from 0.05 to 50% by weight.

[0031] (B1) component's specific content is determined according to the content of the above (A) component and the ratio of the content of the (B1) component per 100 parts by weight of the (B1) component. Preferably, it is 0.1 to 50% by weight, 0.5 to 50% by weight, 0.8 to 50% by weight, 3 to 50% by weight, 4 to 50% by weight, 4.5 to 50% by weight, 5 to 50% by weight, 7 to 50% by weight, 9 to 50% by weight, 10 to 50% by weight, 12 to 50% by weight, 14 to 50% by weight, 15 to 50% by weight, 18 to 50% by weight, 20 to 50% by weight, 0.1 to 40% by weight, 0.1 to 45% by weight, 0.1 to 30% by weight, 0.1 to 25% by weight, 0.1 to 23% by weight, 0.1 to 22% by weight, 0.1 to 20% by weight, 0.1 to 17% by weight, 0.1 to 16% by weight, 0.1 to 15% by weight, 0.1 to 13% by weight, or 0.1 to 12% by weight in total.

[0032] (B2) component's specific content is determined according to the content of the above (A) component and the ratio of the content of the (B2) component per 100 parts by weight of the (B2) component. Preferably, it is 0.1 to 10% by weight, 0.2 to 10% by weight, 0.25 to 10% by weight, 0.3 to 10% by weight, 0.45 to 10% by weight, 0.5 to 10% by weight, 0.6 to 10% by weight, 0.85 to 10% by weight, 0.9 to 10% by weight, 1 to 10% by weight, 0.1 to 5% by weight, 0.1 to 3% by weight, 0.1 to 2.5% by weight, 0.1 to 2% by weight, 0.1 to 1.4% by weight, or 0.1 to 1.2% by weight.

[0033] (B3) component's specific content is determined according to the content of the above (A) component and the ratio of the content of the (B3) component per 100 parts by weight of the (B3) component. Preferably, in total, it is 0.05 to 50% by weight, 0.08 to 50% by weight, 0.1 to 50% by weight, 0.25 to 50% by weight, 0.28 to 50% by weight, 0.5 to 50% by weight, 0.7 to 50% by weight, 0.8 to 50% by weight, 0.9 to 50% by weight, 1 to 50% by weight, 3 to 50% by weight, 4 to 50% by weight, 4.5 to 50% by weight, 5 to 50% by weight, 5.2 to 50% by weight, 7 to 50% by weight, 8 to 50% by weight, 9 to 50% by weight, 10 to 50% by weight, 13 to 50% by weight, 14 to 50% by weight, 15 to 50% by weight, 20 to 50% by weight, 23 to 50% by weight, 24 to 50% by weight, 0.05 to 50% by weight, 0.05 to 40% by weight, 0.05 to 35% by weight, 0.05 to 30% by weight, 0.05 to 26% by weight, 0.05 to 20% by weight, 0.05 to 16% by weight, 0.05 to 12% by weight, 0.05 to 11% by weight, 0.05 to 7% by weight, 0.05 to 6% by weight, 0.05 to 5% by weight, 0.05 to 2.5% by weight, 0.05 to 2% by weight, 0.05 to 1.5% by weight, 0.05 to 1% by weight, 0.05 to 0.9% by weight, 0.05 to 0.6% by weight, or 0.05 to 0.35% by weight.

[0034] (C) Starch and / or lactose The solid pharmaceutical composition of the present disclosure can further contain starch and / or lactose as the (C) component (hereinafter also referred to as the "(C) component").

[0035] The starch is not particularly limited, and examples thereof include corn starch and potato starch, and preferably corn starch.

[0036] The content of the (C) component in the solid pharmaceutical composition of the present disclosure is, in total, for example, 3 to 40% by weight, preferably 10 to 35% by weight.

[0037] Other components The solid pharmaceutical composition of the present disclosure may contain additives and / or bases as other components in addition to the above components, as long as the effects of the present disclosure are not impaired.

[0038] The additives and bases are not particularly limited as long as they are pharmaceutically acceptable. Examples include excipients (such as lactose, etc.), binders (such as sodium alginate, polyvinylpyrrolidone, etc.), disintegrants (such as agar, etc.), lubricants (such as sucrose fatty acid esters, etc.), coloring agents (such as caramel, gardenia pigment, titanium oxide, iron oxide, etc.), preservatives (such as L-ascorbic acid, etc.), antiseptics (such as benzoates, paraoxybenzoic acid esters, etc.), pH adjusters (such as potassium carbonate, sodium bicarbonate, etc.), surfactants (such as saponin, lecithin, sucrose fatty acid esters, etc.), coating agents (such as shellac, macrogol, carnauba wax, etc.). These additives and bases may be used alone or in combination of multiple types. Also, the content of these additives and bases is appropriately set according to the type of additives and bases used, etc., as long as it can be formulated as a solid pharmaceutical composition.

[0039] In addition to Lizawa Ventilation Decoction plus Flos Magnoliae Extract, the solid pharmaceutical composition of the present disclosure may also contain other nutritional components and / or pharmacological components as needed. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable. Examples include antacids, stomachics, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, caffeine compounds, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drug extracts, vitamins, menthols, etc. These nutritional components and pharmacological components may be used alone or in combination of multiple types. Also, the content of these components is appropriately set according to the type of components used, etc.

[0040] Form of preparation Regarding the dosage form of the solid pharmaceutical composition of the present disclosure, there is no particular limitation as long as it is a solid preparation. Specifically, tablets, pills, powders, fine granules, granules (including granules filled in capsules), etc. can be mentioned. Since the solid pharmaceutical composition of the present disclosure is excellent in discoloration suppression, even powders, fine granules, and granules with a large specific surface area can effectively suppress discoloration.

[0041] The tablets produced from the solid pharmaceutical composition of the present disclosure may be plain tablets (naked tablets) or coated tablets with a coating applied to the surface for the purposes of stabilizing the drug and flavoring and / or masking odors, etc. Since the solid pharmaceutical composition of the present disclosure is excellent in discoloration suppression, even plain tablets without a coating on the surface can effectively suppress discoloration.

[0042] Manufacturing method The solid pharmaceutical composition of the present disclosure can be produced according to the usual formulation methods employed in the pharmaceutical field using the above-mentioned component (A) and component (B), and component (C) and / or other components formulated as necessary.

Examples

[0043] Hereinafter, the present disclosure will be specifically described by way of examples, but the present disclosure is not limited to these examples.

[0044] Test examples 1. Preparation of Lizetongqi Decoction plus Flos Magnoliae Extract powder As raw crude drugs, 4.0 parts by weight of mugwort (the same applies hereinafter), 1.0 part of Japanese pepper, 3.0 parts of sophora flavescens, 1.0 part of peony, 3.0 parts of cinnamon bark, 4.0 parts of white peony, 3.0 parts of aconite, 1.0 part of ginger, 3.0 parts of angelica, 1.0 part of ginseng, 1.0 part of zingiber officinale, 3.0 parts of cardamom, and 1.0 part of licorice, 3.0 parts of cinnabar were used. After these were ground, 10 times the weight of water was used for extraction at about 95°C for 30 minutes, and centrifuged to obtain an extract. The extract was concentrated under reduced pressure and dried using a spray dryer to obtain a powdered extract of Lize Tongqi Decoction plus magnolia flower. The drying by the spray dryer was performed by dropping the extract onto an atomizer rotating at 10,000 rpm and supplying hot air of 140°C air.

[0045] 2. Preparation of solid pharmaceutical composition Solid pharmaceutical compositions having the compositions shown in Tables 1 to 4 were prepared. Specifically, the powdered extract of Lize Tongqi Decoction plus magnolia flower and the predetermined components shown in Tables 1 to 4 were mixed in a plastic bag, and then passed through a sieve to prepare a powdered solid pharmaceutical composition (powder).

[0046] 3. Discoloration inhibition test 3.0 g of the solid pharmaceutical composition was evenly spread into a circular shape with a diameter of 10 cm and stored under the conditions of 40°C and 75% RH for 24 hours. Regarding immediately after the preparation and after storage of the solid pharmaceutical composition, the color was measured with a spectrophotometer (CM-700d), and based on the following formula, the color change amount (ΔE*ab) after storage was measured. The results are shown in Tables 1 to 4.

[0047]

Equation

[0048] Furthermore, when the ΔE*ab of Comparative Example 1 (when containing corn starch as component (C)) and Comparative Example 5 (when containing lactose as component (C)) was set to 100%, the ratio (%) of ΔE*ab of each Example and each Comparative Example was derived as the "discoloration index". When the discoloration index is less than 100%, it indicates that discoloration is suppressed, and the smaller the discoloration index, the higher the discoloration suppression effect. The results are shown in Tables 1 to 4.

[0049]

Table 1A

[0050]

Table 1B

[0051]

Table 2A

[0052]

Table 2B

[0053]

Table 3

[0054]

Table 4

[0055] As shown in Comparative Examples 1 and 5, discoloration was observed in the solid pharmaceutical composition containing Lizawa Ventilation Decoction plus Flos Magnoliae Extract after storage. Also, as shown in Comparative Examples 2 to 4 and 6, even when dextrin was blended with Lizawa Ventilation Decoction plus Flos Magnoliae Extract, no discoloration inhibitory effect was observed, and rather, it deteriorated. In contrast, as shown in Examples 1 to 57, it was confirmed that by blending a predetermined compound such as a cellulose compound, a stearate, or a silicate compound in addition to Lizawa Ventilation Decoction plus Flos Magnoliae Extract, the discoloration inhibitory property can be improved.

[0056] Formulation examples Granules having the formulation shown in Table 5 were prepared. For any of the formulations of the granules, by blending a predetermined compound such as a cellulose compound, a stearate, and / or a silicate compound in addition to Lizetongqi Decoction plus Magnolia Flower Extract, the discoloration inhibitory property could be improved.

[0057]

Table 5

Claims

1. A solid pharmaceutical composition comprising (A) Lizawa Ventilation Decoction plus magnolia flower extract, and (B) a predetermined compound selected from the group consisting of (B1) a cellulose compound, (B2) a stearate, and (B3) a silicate compound.

2. The solid pharmaceutical composition according to Claim 1, wherein the component (B1) is selected from the group consisting of cellulose, crystalline cellulose, calcium carboxymethylcellulose, croscarmellose calcium, and hydroxypropylcellulose.

3. The solid pharmaceutical composition according to Claim 1 or 2, wherein the component (B3) is selected from the group consisting of silicon dioxide, aluminum silicate, magnesium aluminometasilicate, and talc.

4. The solid pharmaceutical composition according to Claim 1 or 2, wherein the content of the component (B) per 100 parts by weight of the component (A) is 0.05 to 70 parts by weight in total.

5. The solid pharmaceutical composition according to Claim 1 or 2, wherein the content of the component (A) is 50 to 95% by weight.

6. The solid pharmaceutical composition according to Claim 1 or 2, wherein the content of the component (B) is 0.05 to 50% by weight in total.

7. The solid pharmaceutical composition according to Claim 1 or 2, further comprising (C) starch and / or lactose.

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