Composition for granule or tablet

Abstract

To provide a formulation technique that suppresses friability of solid preparations containing a Kampo extract.SOLUTION: By blending menthol with a Kampo extract preparation, the Kampo extract preparation exhibits reduced friability when formulated as granules or tablets, where the Kampo extract preparation contains a Kampo extract selected from the group consisting of Kakkontokasenkyushin'i extract and Reitakutsukitokashin'i extract.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a composition for granules or tablets containing a Chinese herbal extract.

Background Art

[0002] Generally, solid preparations such as granules and tablets are dosage forms that are granulated and / or molded, and thus require additives for forming the dosage form. Similarly, Chinese herbal extract preparations also require additives for formulating into the dosage form. On the other hand, since the daily dosage of the active ingredient in Chinese herbal extract preparations is large, the single-dose amount is very large compared to ordinary synthetic pharmaceuticals. Therefore, due to the need to incorporate an effective amount of Chinese herbal extract while ensuring ease of administration, there is a limit to the proportion of additives that can be incorporated into Chinese herbal extract preparations. Among the additives incorporated into granules and tablets, there are those that impart desired mechanical properties to the preparation. However, in the case of Chinese herbal extract preparations, it is difficult to sufficiently possess the desired mechanical properties due to the limit of the blending amount of the additives.

[0003] One of such mechanical properties is suppression of wear. Patent Document 1 describes that in order to suppress wear of a solid preparation containing a Chinese herbal extract, saccharides, crystalline cellulose, and a disintegrant are blended in predetermined amounts together with the Chinese herbal medicine extract.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, the technology of Patent Document 1 has a large total amount of components contributing to the improvement of wear resistance and significant compositional limitations. Also, considering that the granulated product is prone to production loss due to wear during sieving, it is desirable that wear be suppressed not only in tablets formed with a strong tableting pressure but also at the granulated product stage. For this reason, a new formulation technology for suppressing wear of solid preparations containing crude herbal extracts is desired.

[0006] Therefore, an object of the present invention is to provide a formulation technology for suppressing wear of solid preparations containing crude herbal extracts.

Means for Solving the Problems

[0007] As a result of intensive studies, the present inventor has found that by blending menthol into a crude herbal extract preparation containing Gegen Decoction plus Japanese wild ginger and / or Magnolia officinalis extract and / or Lizawa Ventilation Decoction plus Magnolia officinalis extract, the wear degree when formulated into granules or tablets is reduced. The present invention has been completed through further studies based on these findings.

[0008] That is, the present invention provides inventions in the following aspects. Item 1. A composition for granules or tablets, comprising a crude herbal extract selected from the group consisting of Gegen Decoction plus Japanese wild ginger and Magnolia officinalis extract and Lizawa Ventilation Decoction plus Magnolia officinalis extract, and menthol. Item 2. The composition according to Item 1, wherein the menthol is contained in an amount of 0.01 parts by weight or more per 100 parts by weight of the total amount of the crude herbal extract. Item 3. The composition according to Item 1 or 2, wherein the content of the menthol is 0.01% by weight or more. Item 4. The composition according to any one of Items 1 to 3, wherein the total amount of the crude herbal extract is 30% by weight or more. Item 5. The composition according to any one of Items 1 to 4, further comprising saccharides.

Effects of the Invention

[0009] According to the present invention, a formulation technology for suppressing wear of solid preparations containing crude herbal extracts is provided.

Modes for Carrying Out the Invention

[0010] The composition for granules or tablets of the present disclosure is characterized by containing a Chinese herbal extract (hereinafter also referred to as "predetermined Chinese herbal extract") selected from the group consisting of Gegen Decoction plus Kawakyu Magnolia Flower Extract and Lizhong Tongqi Decoction plus Magnolia Flower Extract, and menthol. Hereinafter, the composition of the present disclosure will be described in detail. In this specification, a numerical range indicated by two numerical values and "~" shall include these 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.

[0011] Kakkotō plus Magnolia officinalis Rehder et Wilson extract and Bupleuri Decoction for Ventilating the Lung plus Magnolia officinalis Rehder et Wilson extract As Gegen Decoction plus Kawakyu Magnolia Flower, the Chinese herbal prescription described in "New Guide to General Chinese Herbal Prescriptions" (supervised by Yukihiro Goda and Takashi Hakozuka, edited by the Japan Society of Chinese Herbal Medicine Manufacturers, published by Jihou Co., Ltd.) is preferable, and it includes a mixed crude drug consisting of Puerariae Radix, Ephedrae Herba, Cinnamomi Ramulus, Glycyrrhizae Radix, Paeoniae Radix Alba, Glycyrrhizae Radix, Zingiberis Rhizoma, Scutellariae Radix, and Magnoliae Flos.

[0012] As the preferable component ratio of each crude drug constituting Gegen Decoction plus Kawakyu Magnolia Flower, there may be mentioned 2 to 8 parts by weight of Puerariae Radix, 1.5 to 4 parts by weight of Ephedrae Herba, 1.5 to 4 parts by weight of Cinnamomi Ramulus, 1 to 3 parts by weight of Glycyrrhizae Radix, 1 to 3 parts by weight of Paeoniae Radix Alba, 1 to 2 parts by weight of Glycyrrhizae Radix, 0.5 to 1.5 parts by weight of Zingiberis Rhizoma, 1 to 3 parts by weight of Scutellariae Radix, and 1 to 3 parts by weight of Magnoliae Flos.

[0013] As Lizhong Tongqi Decoction plus Magnolia Flower, the Chinese herbal prescription described in "Standards for the Manufacture and Sale of Approved General Chinese Herbal Preparations (Ministry of Health, Labour and Welfare, Pharmaceutical and Life Hygiene Bureau, April 1, 2017)" is preferable, and it includes a mixed crude drug consisting of Alpiniae Oxyphyllae Fructus, Zanthoxyli Pericarpium, Bupleuri Radix, Ephedrae Herba, Cinnamomi Ramulus, Paeoniae Radix Alba, Glycyrrhizae Radix, Zingiberis Rhizoma, Puerariae Radix, Zingiberis Rhizoma Recens, Puerariae Radix, and Magnoliae Flos (Paeoniae Radix Alba may be omitted), more preferably a mixed crude drug consisting of Alpiniae Oxyphyllae Fructus, Zanthoxyli Pericarpium, Bupleuri Radix, Ephedrae Herba, Cinnamomi Ramulus, Paeoniae Radix Alba, Glycyrrhizae Radix, Zingiberis Rhizoma, Puerariae Radix, Zingiberis Rhizoma Recens, and Magnoliae Flos.

[0014] As the preferable component ratio of each crude drug constituting the Lizawa Ventilation Decoction plus Magnolia Flower, there may be mentioned 2 to 4 parts by weight of Alpinia officinarum, 0.5 to 1 part by weight of Zanthoxylum piperitum, 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 Cinnamomum cassia, 2 to 4 parts by weight of Paeonia lactiflora, 1.5 to 3 parts by weight of Glycyrrhiza glabra, 0.5 to 1 part by weight of Zingiber officinale, 1.5 to 3 parts by weight of Pueraria lobata, 0.5 to 1 part by weight of Atractylodes lancea, 0.5 to 1 part by weight of Asarum sieboldii, 1.5 to 3 parts by weight of Aucklandia lappa, 0.5 to 1 part by weight of Glycyrrhiza uralensis, and 1.5 to 3 parts by weight of Magnolia flower.

[0015] The Gegen Decoction plus Chuanxiong and Magnolia Flower Extract and the Lizawa Ventilation Decoction plus Magnolia Flower Extract may each be obtained as an extract solution by subjecting the above-mentioned mixed crude drugs to an extraction treatment and concentrating the obtained extract solution as necessary, or may be obtained as an extract powder by subjecting the extract solution to a drying treatment.

[0016] In the production of each of the Gegen Decoction plus Chuanxiong and Magnolia Flower Extract and the Lizawa Ventilation Decoction plus Magnolia Flower Extract, although the extraction solvent used for the extraction treatment is not particularly limited, examples thereof include water or aqueous ethanol, and preferably water. Also, the drying treatment is not particularly limited, and known methods such as a spray drying method, a method of adding a suitable adsorbent (for example, anhydrous silicic acid, starch, etc.) to a soft extract with an increased concentration of the extract solution to obtain an adsorbed powder, etc. may be mentioned.

[0017] In the composition of the present disclosure, the total amount of a predetermined Kampo extract (referring to the amount converted to a dry extract; the same applies hereinafter) is not particularly limited, but examples thereof include 30% by weight or more, specifically 30 to 99% by weight. The composition of the present disclosure can contain a large amount of Kampo extract in order to suppress the abrasion degree when menthol blended together with the predetermined Kampo extract is formulated as granules or tablets. From such a viewpoint, the total content of the predetermined Kampo extract in the composition of the present disclosure is preferably 30 to 99% by weight, more preferably 40 to 99% by weight, still more preferably 50 to 99% by weight, even more preferably 55 to 99% by weight, 58 to 99% by weight, 58 to 90% by weight, 58 to 80% by weight, 58 to 70% by weight, or 58 to 65% by weight.

[0018] Note that the amount in terms of dry extract is the amount itself when dry extract (powdered extract) is used, and when 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 adsorbents added during production, it is the amount excluding such additives.

[0019] Menthol As menthol, any of the d-form, l-form, and dl-form may be used. Among these menthols, preferably the l-form and dl-form are mentioned, and more preferably the l-form is mentioned. Also, as the compounding material of menthol, either purified menthol or essential oil containing menthol may be used, and preferably purified menthol is mentioned.

[0020] The content of menthol in the composition of the present disclosure is not particularly limited and can be appropriately set according to the degree required for the effect of suppressing the abrasion degree when formulated as granules or tablets. For example, the content of menthol in the composition of the present disclosure is, per 100 parts by weight of the total amount of a predetermined crude drug extract, 0.01 part by weight or more. From the viewpoint of further enhancing the effect of suppressing the abrasion degree when formulated as granules or tablets, the content of menthol per 100 parts by weight of the total amount of a predetermined crude drug extract is preferably 0.15 part by weight or more, or 0.5 part by weight or more, more preferably 1 part by weight or more, 1.5 parts by weight or more, 3 parts by weight or more, 5 parts by weight or more, 7 parts by weight or more, 9 parts by weight or more, 11 parts by weight or more, 13 parts by weight or more, or 15 parts by weight or more. The content of menthol in the composition of the present disclosure is not particularly limited even at its upper limit, but as the content of menthol per 100 parts by weight of the total amount of a predetermined crude drug extract, for example, 30 parts by weight or less, 26 parts by weight or less, 22 parts by weight or less, 18 parts by weight or less, 16 parts by weight or less, 14 parts by weight or less, 12 parts by weight or less, 10 parts by weight or less, 8 parts by weight or less, 6 parts by weight or less, 4 parts by weight or less, or 2 parts by weight or less is mentioned.

[0021] When the specified Chinese herbal extract is Gegen Decoction plus Japanese wild ginger and magnolia flower extract, the content of menthol per 100 parts by weight of Gegen Decoction plus Japanese wild ginger and magnolia flower extract is 0.01 part by weight or more, preferably 0.05 part by weight or more, 0.1 part by weight or more, more preferably 0.5 part by weight or more, 1 part by weight or more, 1.5 parts by weight or more, 3 parts by weight or more, 5 parts by weight or more, 7 parts by weight or more, 9 parts by weight or more, still more preferably 11 parts by weight or more, 13 parts by weight or more, or 15 parts by weight or more. For example, 30 parts by weight or less, 26 parts by weight or less, 22 parts by weight or less, 18 parts by weight or less, 16 parts by weight or less, 14 parts by weight or less, 12 parts by weight or less, 10 parts by weight or less, 8 parts by weight or less, 6 parts by weight or less, 4 parts by weight or less, or 2 parts by weight or less.

[0022] When the specified Chinese herbal extract is Lizawa Ventilating Decoction plus magnolia flower extract, the content of menthol per 100 parts by weight of Lizawa Ventilating Decoction plus magnolia flower extract is 0.01 part by weight or more, preferably 0.05 part by weight or more, 0.1 part by weight or more, more preferably 0.15 part by weight or more, 0.5 part by weight or more, still more preferably 1 part by weight or more, or 1.5 parts by weight or more. For example, 14 parts by weight or less, 12 parts by weight or less, or 10 parts by weight or less, preferably 8 parts by weight or less, 6 parts by weight or less, 4 parts by weight or less, or 2 parts by weight or less.

[0023] The specific content of menthol in the composition of the present disclosure is not particularly limited either, and can be appropriately set according to the degree required for the effect of suppressing the abrasion degree when formulated as granules or tablets. For example, the specific content of menthol in the composition of the present disclosure is 0.01% by weight or more, preferably 0.08% by weight or more, 0.5% by weight or more, 0.8% by weight or more, 2% by weight or more, 3% by weight or more, 4% by weight or more, 5% by weight or more, 6% by weight or more, 7% by weight or more, or 8% by weight or more. The specific content of menthol in the composition of the present disclosure is not particularly limited even in terms of its upper limit. For example, 10% by weight or less, 7.5% by weight or less, 4.5% by weight or less, 2.5% by weight or less, 1.5% by weight or less, or 1.3% by weight or less.

[0024] When the predetermined Chinese herbal extract is Gegen Decoction plus Japanese wild ginger and magnolia flower extract, the specific content of menthol in the composition of the present disclosure is 0.01% by weight or more, preferably 0.08% by weight or more, 0.5% by weight or more, 0.8% by weight or more, 2% by weight or more, 3% by weight or more, 4% by weight or more, or 5% by weight or more, preferably 6% by weight or more, 7% by weight or more, or 8% by weight or more, and for example, 10% by weight or less, 7.5% by weight or less, 4.5% by weight or less, 2.5% by weight or less, 1.5% by weight or less, or 1.3% by weight or less.

[0025] When the predetermined Chinese herbal extract is Lizawa Ventilating Decoction plus magnolia flower extract, the specific content of menthol in the composition of the present disclosure is 0.01% by weight or more, preferably 0.08% by weight or more, 0.5% by weight or more, or 0.8% by weight or more, and for example, 7.5% by weight or less, preferably 4.5% by weight or less, 2.5% by weight or less, 1.5% by weight or less, or 1.3% by weight or less.

[0026] Note that the content of menthol represents its own content when purified menthol is used, and represents the amount of menthol contained in the essential oil blended when an essential oil containing menthol is used as a blending material for menthol.

[0027] Other active ingredients In addition to the above-mentioned predetermined Chinese herbal extract and menthol, the composition of the present disclosure may or may not contain one or more additives and / or bases according to the dosage form. Additives and bases, regardless of whether they are contained or not, are not particularly limited as long as they are pharmaceutically acceptable. Examples include excipients, binders, disintegrants, lubricants, plasticizers, dispersants, emulsifiers, wetting agents, stabilizers, coating agents, brightening agents, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, ultraviolet light protectants, preservatives, flavoring agents, fragrances, powders, pigments, chelating agents, and the like. When the composition of the present disclosure contains additives and / or bases, these additives and bases may be used alone or in combination of two or more. Also, the content of these additives and bases is appropriately set according to the types of additives and bases used, the dosage form of the composition, and the like.

[0028] In a preferred embodiment, the composition of the present disclosure can contain saccharides used as excipients and / or binders, etc. Such saccharides include starches such as corn starch, potato starch, wheat starch, and rice starch; celluloses such as crystalline cellulose, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, carboxymethylcellulose calcium, hydroxypropylcellulose (such as low-substitution hydroxypropylcellulose); monosaccharides or disaccharides such as glucose, fructose, lactose, and sucrose.

[0029] When the composition of the present disclosure contains an excipient, it may also contain excipients other than the above-mentioned saccharides. Such excipients include aluminum silicate, magnesium aluminometasilicate, talc, silicon dioxide, light anhydrous silicic acid, hydrous silicon dioxide, synthetic aluminum silicate, magnesium stearate, and the like.

[0030] In addition to the above-mentioned predetermined herbal extract and menthol, the composition of the present disclosure may or may not contain other pharmacological components and / or nutritional components. The types of pharmacological components and nutritional components, regardless of whether they are contained or not, are not particularly limited. For example, antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, caffeine, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drugs, crude drug extract powders, vitamins, etc. may be mentioned. When the composition of the present disclosure contains other pharmacological components and / or nutritional components, these pharmacological components and nutritional components may be used alone or in combination of two or more. Also, the content of these pharmacological components and / or nutritional components may be appropriately set from known ones according to the types of pharmacological components and / or nutritional components to be used, etc.

[0031] Form of preparation The dosage form of the composition of the present disclosure is not particularly limited, provided that it is for granules or tablets. For example, powders (non-granulated substances) intended to be formulated as granules or tablets; granules intended to be formulated as tablets; granules as the final form; tablets, etc. may be mentioned. Also, when the composition of the present disclosure is a tablet, it may be a coated tablet or an uncoated tablet.

[0032] To prepare the composition of the present disclosure in the above dosage form, the above-mentioned predetermined herbal extract and menthol, as well as additives, bases, pharmacological components, and / or nutritional components added as necessary, may be used to formulate according to the usual formulation methods employed in the pharmaceutical field.

Examples

[0033] Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited to these examples.

[0034] [Test example] Preparation of Kakkotō plus Magnolia officinalis Rehder et Wilson extract powder As crude drugs, 4.0 parts by weight (the same hereinafter) of Angelica dahurica, 4.0 parts of Cinnamon Twig, 3.0 parts of Bupleurum Root, 2.0 parts of Coptis Rhizome, 2.0 parts of Paeonia Root, 2.0 parts of Licorice Root, 1.0 part of Ginger, 3.0 parts of Ginseng, and 3.0 parts of Asarum were weighed out. Approximately 10 times the total weight of the crude drugs was added with water, and extraction was carried out at about 95°C for 30 minutes. After centrifugation, an extract was obtained. The extract was concentrated under reduced pressure and dried using a spray dryer. The drying by the spray dryer was carried out by dropping the extract onto an atomizer with a rotation speed of 13,000 rpm and supplying hot air of 140°C air.

[0035] Preparation of Bupleuri Decoction for Ventilating the Lung plus Magnolia officinalis Rehder et Wilson extract powder As crude drugs, 4.0 parts by weight (the same hereinafter) of Atractylodes lancea, 1.0 part of Prickly Ash, 3.0 parts of Polygonum bistorta, 1.0 part of Cinnamon Twig, 3.0 parts of Aucklandia lappa, 4.0 parts of Bupleurum falcatum, 3.0 parts of Phellodendron amurense, 1.0 part of Ginger, 3.0 parts of Ledebouriella seseloides, 1.0 part of Bupleurum Root, 1.0 part of Zingiber mioga, 3.0 parts of Angelica dahurica, 1.0 part of Licorice Root, and 3.0 parts of Asarum were weighed out. 10 times the total weight of the crude drugs was added with water, and extraction was carried out at about 95°C for 30 minutes. After centrifugation, an extract was obtained. The extract was concentrated under reduced pressure and dried using a spray dryer. The drying by the spray dryer was carried out by dropping the extract onto an atomizer with a rotation speed of 13,000 rpm and supplying hot air of 140°C air.

[0036] Manufacture of granules The granules shown in Table 1 and Table 2 were prepared. Specifically, pulverized purified menthol and saccharides (corn starch or lactose) were added to and mixed with Gegen Decoction plus Japanese wild ginger extract powder or Lizawa Tongqi Decoction plus Japanese wild ginger extract powder, and after sieving through a stainless steel mesh (mesh size: 500 μm), granules were prepared by the wet granulation method.

[0037] Abrasion test The obtained granules were sieved through a stainless steel mesh with an opening of 355 μm, and the granules with a particle size of 180 μm on and 355 μm passing were classified. Approximately 3 g of the classified granules were put into the drum of a wear test apparatus (Tsutsui Rikagaku Kikai Co., Ltd., model number TFF-03) and rotated 300 times, and then the granules were taken out. The taken-out granules were sieved through a stainless steel mesh with an opening of 180 μm, and the weight A of the granules on 180 μm and the weight B of the granules passing 180 μm were measured. The wear rate (%) was derived by the calculation formula B / (A + B)×100. The results are shown in Table 1 and Table 2.

[0038]

Table 1

[0039]

Table 2

[0040] As shown in Tables 1 and 2, by blending menthol into a predetermined herbal extract, the wear was suppressed in a concentration-dependent manner of menthol.

[0041] [Prescription example] Granules with the formulations shown in Tables 3 and 4 were prepared. The wear of all the granules was suppressed by the blending of menthol.

[0042]

Table 3

[0043]

Table 4

Claims

1. A composition for granules or tablets, comprising a Kampo extract selected from the group consisting of Kakkonto-ka-Senkyu-Shin'i extract and Reizei-tsuuki-to-ka-Shin'i extract, and menthol.

2. The composition according to claim 1, comprising 0.01 part by weight or more of said menthol per 100 parts by weight of the total amount of said herbal extract.

3. The composition according to claim 1 or 2, wherein the menthol content is 0.01% by weight or more.

4. The composition according to claim 1 or 2, wherein the total amount of the herbal extract is 30% by weight or more.

5. The composition according to claim 1 or 2, further comprising a sugar.

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