Tablet composition

Abstract

To provide a new formulation technique that can improve the hardness, disintegrability, and wear resistance of a tablet including bofu-tsusho-san extract.SOLUTION: A tablet composition includes bofu-tsusho-san extract. A herbal blend used for the extraction of the bofu-tsusho-san extract includes 3-22 pts.wt. of raw ginger relative to 100 pts.wt. of the herbal blend. Such a tablet composition makes it possible to improve the hardness, disintegrability, and wear resistance after tabletting.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a tablet composition containing Saposhnikoviae and Gardeniae Formula Extract. More specifically, the present invention relates to a tablet composition containing Saposhnikoviae and Gardeniae Formula Extract, which can improve the hardness, disintegration property and abrasion resistance after tabletting.

Background Art

[0002] Saposhnikoviae and Gardeniae Formula is a Chinese herbal medicine taken for the purpose of improving obesity and metabolic syndrome. Since the extract preparations of Saposhnikoviae and Gardeniae Formula are not only prescribed in hospitals but also commercially available, due to their easy availability, commercially available drugs are particularly widely used.

[0003] Saposhnikoviae and Gardeniae Formula extract preparations are often provided in tablet form from the viewpoint of making taking easier. For this reason, various formulations for improving tablet properties such as hardness and disintegration property have been studied for tablets containing Saposhnikoviae and Gardeniae Formula Extract.

[0004] For example, Patent Document 1 describes blending pantethine into an extract obtained from Saposhnikoviae and Gardeniae Formula consisting of 1.2 parts by weight (the same hereinafter) of Ledebouriella seseloides, 1.2 parts of Paeonia lactiflora, 1.2 parts of Gentiana scabra, 1.2 parts of Schizonepeta tenuifolia, 1.2 parts of Rheum officinale, 1.2 parts of Mentha haplocalyx, 1.2 parts of Zingiber officinale, 1.2 parts of Cnidium officinale, 1.2 parts of Saposhnikovia divaricata, 1.2 parts of Ephedra sinica, 1.5 parts of Gypsum fibrosum, 1.5 parts of Atractylodes lancea, 2.0 parts of Anemarrhena asphodeloides, 2.0 parts of Platycodon grandiflorum, 2.0 parts of Curcuma longa, 2.0 parts of Glycyrrhiza glabra, 2.0 parts of Gypsum rubrum and 3.0 parts of Haliotis diversicolor for the purpose of providing a tablet containing a Chinese herbal medicine having excellent effects in terms of mechanical strength and disintegration property.

[0005] Patent Document 2 describes blending saccharides, crystalline cellulose and a disintegrant into Saposhnikoviae and Gardeniae Formula Extract-F manufactured by Alps Pharmaceutical Industry Co., Ltd. so that each component has a predetermined ratio for the purpose of providing a solid preparation having practical hardness and abrasion degree, being non-sticky and having excellent disintegration property.

[0006] Patent Document 3 describes a formulation containing crude drugs that exhibits excellent tableting properties, ensures sufficient formulation hardness, and does not experience delays in disintegration time, even when containing a high concentration of crude drug dried extract. This formulation is described as being formulated by combining a dried extract of Bofu-tsusho-san (manufactured by Alps Pharmaceutical Co., Ltd., crude drug ratio: Platycodon grandiflorus 2 parts, Angelica dahurica 2 parts, Licorice 2 parts, Scutellaria baicalensis 2 parts, Gypsum 2 parts, Rhubarb 2 parts, Angelica acutiloba 1.2 parts, Paeonia lactiflora 1.2 parts, Cnidium officinale 1.2 parts, Gardenia fruit 1.2 parts, Forsythia suspensa 1.2 parts, Mentha arvensis 1.2 parts, Schizonepeta tenuifolia 1.2 parts, Saposhnikovia divaricata 1.2 parts, Ephedra sinica 1.2 parts, Zingiber officinale 0.4 parts, Talc 3 parts, Sodium sulfate 1.5 parts) with a plant-derived hard wax, magnesium aluminometasilicate, and sodium salt of a polyvalent carboxymethyl ether crosslinked product of cellulose. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] International Publication No. 2009 / 093736 [Patent Document 2] Japanese Patent Publication No. 2012-001473 [Patent Document 3] Japanese Patent Publication No. 2012-87055 [Overview of the project] [Problems that the invention aims to solve]

[0008] To date, improvements in properties such as hardness, disintegration, and / or abrasion resistance of tablets containing Bofu-tsusho-san extract have focused on selecting specific additives and their combinations, as well as optimizing the ratio of tablet composition components. However, the improvement of tablet properties using these methods is limited, and new approaches are needed to further enhance these properties.

[0009] Therefore, the object of the present invention is to provide a new formulation technology that can improve the hardness, disintegration, and abrasion resistance of tablets containing Bofu-tsusho-san extract. [Means for solving the problem]

[0010] As a result of diligent research, the inventors unexpectedly discovered that using fresh ginger as one of the constituent herbs of Bofu-tsusho-san, and using 3 to 22 parts by weight of fresh ginger per 100 parts by weight of the mixture of all constituent herbs of Bofu-tsusho-san (herbal preparation), can improve the hardness, disintegration, and abrasion resistance of the Bofu-tsusho-san extract after tablet manufacturing. This invention was completed by further research based on this finding.

[0011] In other words, the present invention provides inventions in the following embodiments. Item 1. A tablet composition containing Bofu-tsusho-san extract, A tablet composition wherein the crude drug preparation used to extract the Bofu-tsusho-san extract contains 3 to 22 parts by weight of fresh ginger per 100 parts by weight of the crude drug preparation. Item 2. The tablet composition according to Item 1, comprising 65% by weight or more of the Bofu-tsusho-san extract. Item 3. A tablet comprising the tablet composition described in Item 1 or 2. Item 4. A tablet as described in Item 3, which is an uncoated tablet. [Effects of the Invention]

[0012] The present invention provides a novel formulation technology that can improve the hardness, disintegration, and abrasion resistance of tablets containing Bofu-tsusho-san extract. [Modes for carrying out the invention]

[0013] The tablet composition of the present invention is a tablet composition containing Bofu-tsusho-san extract, characterized in that the herbal preparation used to extract the Bofu-tsusho-san extract contains 3 to 22 parts by weight of fresh ginger per 100 parts by weight of the herbal preparation. This improves the hardness, disintegration, and abrasion resistance after tablet manufacturing. The tablet composition of the present invention will be described in detail below.

[0014] The tablet composition of the present invention contains a predetermined Bofu-tsusho-san extract. The crude drug formulation constituting the predetermined Bofu-tsusho-san used in the present invention contains at least fresh ginger in the above predetermined ratio. In the present invention, "fresh ginger" refers to fresh mature ginger and is different from "ginger" as defined in the Japanese Pharmacopoeia as dried ginger. In other words, the crude drug formulation constituting the predetermined Bofu-tsusho-san used in the present invention differs from the crude drug formulation constituting ordinary Bofu-tsusho-san that contains "ginger" but does not contain "fresh ginger," in that it contains "fresh ginger" in the above predetermined ratio.

[0015] The crude drug formulation constituting Bofu Tsusho San in the present invention can be similar to the crude drug formulation constituting ordinary Bofu Tsusho San, except that it contains raw ginger in the above-mentioned predetermined ratio. According to the "Guide to General Use Kampo Prescriptions" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Kampo Expert Committee of the Japan Pharmaceutical Association, published by Yakugyo Jihosha), the ordinary Bofu Tsusho San consists of Angelica acutiloba, Paeonia lactiflora, Ligusticum chuanxiong, Gardenia jasminoides, Forsythia suspensa, Mentha arvensis, Zingiber officinale, Schizonepeta tenuifolia, Saposhnikovia divaricata, Ephedra sinica, Rheum palmatum, Sodium moniliforme, Atractylodes macrocephala, Platycodon grandiflorus, Scutellaria baicalensis, Glycyrrhiza uralensis, Gypsum, and Talc. Some of the aforementioned crude drugs do not include Atractylodes macrocephala (for example, "Collection of Dosages for Experienced Kampo Prescriptions," edited by Keisetsu Otsuka and Michiaki Yakazu, published by Ido no Nippon Sha), or do not include Scutellaria baicalensis (for example, "Continued Kampo Miscellany," edited by Osaka Yomiuri Shimbun, published by Naniwa Sha). The Bofu Tsusho San extract used in the present invention may be similar to any of these Bofu Tsusho San, and some or all of the "Ginger" is replaced with "Fresh Ginger" in the above-mentioned predetermined ratio.

[0016] The crude drug preparation used in the production of the Bofu-tsusho-san extract in the present invention contains 3 to 22 parts by weight of fresh ginger per 100 parts by weight of the total amount of the crude drug preparation. From the viewpoint of further improving hardness, disintegration and / or abrasion resistance after tableting, the ratio of fresh ginger is preferably 10 to 22 parts by weight, more preferably 15 to 22 parts by weight, even more preferably 18 to 22 parts by weight, and even more preferably 20 to 22 parts by weight.

[0017] Furthermore, the specific amounts of each crude drug constituting Bofu Tsusho San in this invention are not limited as long as the amount of fresh ginger is within the above range, but for example, in accordance with the "Guide to General Use Kampo Prescriptions" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Kampo Expert Committee of the Japan Pharmaceutical Association, published by Yakugyo Jiho Co., Ltd.) and the "17th Revised Japanese Pharmacopoeia", the amounts are 1.2 parts by weight of Angelica root, 1.2 parts by weight of Paeonia lactiflora, 1.2 parts by weight of Ligusticum chuanxiong, 1.2 parts by weight of Gardenia fruit, and Forsythia suspensa. Examples include 1.2 parts by weight of scutellaria root, 1.2 parts by weight of mint, 3 to 22 parts by weight of fresh ginger, 1.2 parts by weight of schizonepeta, 1.2 parts by weight of Saposhnikovia divaricata or 1.2 parts by weight of sea saposhnikovia divaricata, 1.2 parts by weight of ephedra, 1.5 parts by weight of rhubarb, 0.6 to 1.5 parts by weight of sodium sulfate or anhydrous sodium sulfate, 2 parts by weight of Atractylodes macrocephala, 2 parts by weight of Platycodon grandiflorus, 2 parts by weight of Scutellaria baicalensis, 2 parts by weight of licorice, 2 to 3 parts by weight of gypsum, and 3 to 5 parts by weight of talc. Alternatively, in accordance with another book (for example, "Clear Explanation of Kampo Prescriptions," co-authored by Kazuo Nishioka and Shintaro Takahashi, published by Naniwa-sha), all 1.2 parts by weight in the above quantities may be replaced with 1.5 parts by weight.

[0018] A suitable example of the proportions of each crude drug constituting the crude drug formulation used in the production of the Bofu-tsusho-san extract used in the present invention is 1.2 parts by weight of Angelica acutiloba, 1.2 parts by weight of Paeonia lactiflora, 1.2 parts by weight of Ligusticum chuanxiong, 1.2 parts by weight of Gardenia jasminoides, 1.2 parts by weight of Forsythia suspensa, 1.2 parts by weight of Mentha arvensis, 1.2 parts by weight of Schizonepeta tenuifolia, 1.2 parts by weight of Saposhnikovia divaricata, 1.2 parts by weight of Ephedra sinica, 1.5 parts by weight of Rheum palmatum, 0.6 to 1.5 parts by weight of Sodium moniliforme or anhydrous Sodium moniliforme, 2 parts by weight of Atractylodes macrocephala, 2 parts by weight of Platycodon grandiflorus, 2 parts by weight of Scutellaria baicalensis, 2 parts by weight of Glycyrrhiza uralensis, 2 parts by weight of Gypsum, and 3 parts by weight of Talc, with 3 to 22 parts by weight of Zingiber officinale, preferably 10 to 22 parts by weight, more preferably 15 to 22 parts by weight, even more preferably 18 to 22 parts by weight, and even more preferably 20 to 22 parts by weight.

[0019] The Siler and Gypsum Decoction extract used in the present invention can be obtained by extracting the crude drug preparation by a known method. The method for extracting the crude drug preparation may be the same as the conventional method for extracting the Siler and Gypsum Decoction extract. For example, about 10 to 20 times the amount of water is added to the crude drug preparation, and it is stirred and extracted at about 80 to 100 °C for about 1 to 3 hours. After extraction, it is subjected to solid-liquid separation such as centrifugation and filtration to remove solids, and if necessary, it is subjected to concentration treatment or drying treatment to obtain the Siler and Gypsum Decoction extract.

[0020] To obtain the Siler and Gypsum Decoction extract as an extract powder, the extract from which solids have been removed may be concentrated as necessary and then subjected to a drying treatment such as spray drying, vacuum concentration drying, or freeze drying. Also, when subjecting it to a drying treatment (especially drying treatment by spray drying), an excipient may be added to the extract as necessary. By adding an excipient in this way, it becomes possible to shorten the drying time. The type and amount of the excipient added are the same as in the case of producing a general crude drug extract powder.

[0021] The content (in terms of dry weight conversion) of the Siler and Gypsum Decoction extract contained in the tablet composition of the present invention may be, for example, 65% by weight or more. Since the tablet composition of the present invention has an excellent effect of improving tablet properties such as hardness, disintegration property, and abrasion resistance, even if the amount of additives is relatively small, that is, even if the amount of the Siler and Gypsum Decoction extract is relatively large, the tablet properties can be effectively improved. From such a viewpoint, preferred examples of the content of the Siler and Gypsum Decoction extract contained in the tablet composition of the present invention are preferably 68% by weight or more, more preferably 69% by weight or more. The upper limit of the content of the Siler and Gypsum Decoction extract contained in the tablet composition of the present invention is not particularly limited, and for example, 90% by weight or less may be mentioned. From the viewpoint of further enhancing hardness, disintegration property, and / or abrasion resistance, preferably 80% by weight or less, more preferably 75% by weight or less, and still more preferably 72% by weight or less may be mentioned.

[0022] Other ingredients In addition to the above-mentioned predetermined Saposhnikoviae and Ledebouriellae Decoction extract, the tablet composition of the present invention may contain other additives and / or bases suitable for forming into tablets.

[0023] The additives and bases are not particularly limited as long as they are pharmaceutically acceptable. Examples include excipients, binders, disintegrants, lubricants, isotonic agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, polishing agents, water, 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 ray protectants, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents, and the like. These additives 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 type of additives and bases used, etc., as long as it can be formed into tablets.

[0024] Specific examples of the additives and bases include starch (such as potato starch, corn starch, etc.), magnesium stearate, silicate compounds (such as silicon dioxide (light anhydrous silicic acid, etc.), synthetic aluminum silicate, magnesium aluminometasilicate, calcium silicate, magnesium silicate, etc.), synthetic hydrotalcite, anhydrous calcium hydrogen phosphate, carmellose, carmellose calcium, croscarmellose sodium, sodium starch glycolate, crospovidone, etc. From the viewpoint of further improving the hardness, disintegration property and / or wear resistance after tableting, starch (more preferably corn starch), magnesium stearate, and silicate compounds (preferably silicon dioxide, more preferably light anhydrous silicic acid, hydrous silicon dioxide) are preferably mentioned.

[0025] When the tablet composition of the present invention contains starch, the starch content is, for example, 10 to 25% by weight, preferably 15 to 23% by weight, and more preferably 18 to 21% by weight. When the tablet composition of the present invention contains magnesium stearate, the magnesium stearate content is, for example, 0.2 to 2% by weight, preferably 0.5 to 1.5% by weight, and more preferably 0.8 to 1.2% by weight. When the tablet composition of the present invention contains a silicate compound, the silicate compound content is, for example, 2 to 20% by weight, preferably 4 to 17% by weight, and more preferably 7 to 13% by weight. Other additives and base materials are also appropriately set depending on the type of additive and base material used.

[0026] Furthermore, the tablet composition of the present invention may contain other nutritional components and pharmacological components in addition to the Bofu-tsusho-san extract, as needed. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, but examples include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives and hypnotics, antihistamines, caffeines, cardiotonic and diuretic agents, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, menthols, and the like. These nutritional components and pharmacological components may be used individually or in combination of two or more. The content of these components may be appropriately determined depending on the type of component used.

[0027] Formulation The formulation of the tablet composition of the present invention is arbitrary in itself, and is usually prepared as a solid composition. More specifically, the formulations of the tablet composition of the present invention include powders and granules (e.g., granules).

[0028] Manufacturing method The tablet composition of the present invention can be manufactured using Bofu-tsusho-san extract, and optionally added additives, bases, and / or pharmacological components, in accordance with conventional formulation methods used in the pharmaceutical field.

[0029] Purpose The tablet composition of the present invention is used for applications in which it is formed into tablets. The shape and size of tablets produced from the tablet composition of the present invention (tablets containing the tablet composition of the present invention) are not particularly limited. Examples of tablet shapes include round, oval, triangular, and square. In the case of round tablets, the diameter is 6 to 12 mm, preferably 8 to 10 mm. The thickness of the tablet is 3 to 8 mm, preferably 4 to 7 mm. The weight per tablet is 200 to 800 mg, preferably 300 to 600 mg. Because the tablet composition of the present invention has excellent hardness, disintegrability, and abrasion resistance, it is possible to make the thickness of the tablet relatively thin relative to its weight per tablet.

[0030] Tablets produced from the tablet composition of the present invention may be uncoated tablets (unwrapped tablets) or coated tablets with a coating applied to the surface for purposes such as drug stabilization, flavoring, and odor masking. Examples of coated tablets include sugar-coated tablets and film-coated tablets (gastric-coated tablets, enteric-coated tablets) coated with a film containing a water-soluble, enteric-coated, or gastric-coated polymer base. The tablet composition of the present invention has excellent hardness and abrasion resistance, and is therefore physically stable even as an uncoated tablet. The hardness of an uncoated tablet produced from the tablet composition of the present invention can be, for example, 90N or higher, preferably 95N or higher, more preferably 100N or higher, even more preferably 110N or higher, even more preferably 120N or higher, even more preferably 125N or higher, and particularly preferably 130N or higher.

[0031] A method for manufacturing tablets using the tablet composition of the present invention includes, for example, a tableting step of compressing tablets using the tablet composition of the present invention, and may optionally include a mixing step of mixing any components prior to the tableting step, and / or (if the tablet composition is not a granule) a granulation step. The tableting pressure in the tableting step is, for example, 4 to 20 kN, preferably 5 to 15 kN, when manufacturing tablets of 200 to 490 mg / tablet. Since the tablet composition of the present invention has excellent hardness, excellent hardness can be achieved even when manufactured at a low tableting pressure, and therefore, the lifespan of the tablet press can be extended by reducing the load on the tablet press. From the viewpoint of reducing the load on the tablet press, the tableting pressure may be even lower, 4 to 12 kN.

[0032] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[0033] Test example (1) Preparation of Bofu-tsusho-san extract powder Raw herbal medicine formulations with the compositions shown in Table 1 were prepared, extracted with 20 times the weight of water at approximately 100°C for 1 hour, centrifuged to obtain the extract, concentrated under reduced pressure, and dried using a spray dryer to obtain each of the Bofu-tsusho-san extract powders (extracts a-d, extracts A-D). For drying with the spray dryer, the extract was dropped into an atomizer rotating at 10,000 rpm, and hot air at 150°C was supplied.

[0034] (2) Preparation of the tablet composition of Bofu-tsusho-san extract The Bofu-tsusho-san extract powder (extracts a-d, extracts A-D) prepared in (1) above and the additives shown in Table 2 were mixed in the indicated ratios and granulated to obtain a granular tablet composition. (3) Preparation of tablets containing Bofu-tsusho-san extract The tablet composition prepared in (2) above was compressed with a pressure of 12 kN to produce uncoated tablets (300 mg per tablet).

[0035] (4) Tablet characteristics evaluation The tablets manufactured as described in (3) above were evaluated as follows. The results are shown in Table 2.

[0036] (4-1)Hardness The hardness (N) was measured using a load cell type tablet hardness tester at a breaking speed of 0.5 mm / min. (4-2) Disintegration Disintegration was evaluated according to the disintegration test method described in the Japanese Pharmacopoeia (17th edition). Disintegration time (minutes) was derived as the average of the disintegration times (minutes) obtained for six tablets. (4-3) degree of wear Six tablets were placed in a 15 mL tube (outer diameter 17 mm) and shaken for 30 minutes (shaking amplitude 40 mm, shaking speed 150 rpm). Afterwards, the tablets were removed, the weight of the powder adhering to the inner wall of the tube was measured, and the degree of abrasion (%) was derived based on the following formula. Abrasion degree (%) = Weight of powder adhering to the inner wall of the tube (g) / Weight of 6 tablets before shaking (g) × 100

[0037] [Table 1]

[0038] [Table 2]

[0039] As is clear from Tables 1 and 2, tablet compositions containing an extract obtained from a Bofu-tsusho-san herbal medicine preparation containing 3 to 22 parts by weight of fresh ginger per 100 parts by weight were found to significantly improve hardness, disintegration, and abrasion resistance after tableting (Examples 1-4). On the other hand, when the amount of fresh ginger per 100 parts by weight of the Bofu-tsusho-san herbal medicine preparation was 1.1 parts by weight (Comparative Example 3) and when the amount of fresh ginger was 30.9 parts by weight (Comparative Example 4), the significant improvement in tablet properties observed in Examples 1-4 was not observed.

[0040] Furthermore, while a significant improvement in tablet properties was observed when the amount of fresh ginger per 100 parts by weight of the Bofu-tsusho-san crude drug formulation was 4.3 parts by weight (Example 2) compared to 1.1 parts by weight (Comparative Example 3), no improvement in tablet properties was observed when the amount of ginger per 100 parts by weight of the Bofu-tsusho-san crude drug formulation was 4.3 parts by weight (Comparative Example 2) compared to 1.1 parts by weight (Comparative Example 1). Considering this, it was found that the significant improvement in tablet properties observed in Examples 1 to 4 is a unique effect of using fresh ginger in the Bofu-tsusho-san crude drug formulation, and using an amount of 3 to 22 parts by weight per 100 parts by weight.

[0041] Prescription examples Using the Bofu-tsusho-san extract powder (Extract C) prepared in Test Example 1, tablet compositions of the formulations shown in Tables 3-6 were prepared and tablets were manufactured using the same method as in the above Test Example. In all cases, the hardness, disintegration, and abrasion resistance of the tablets were improved compared to cases containing an extract obtained from a Bofu-tsusho-san crude drug formulation in which the amount of fresh ginger per 100 parts by weight was not 3 to 22 parts by weight. Furthermore, in all cases where the Bofu-tsusho-san extract powder was changed to extracts A, B, and D, the hardness, disintegration, and abrasion resistance were improved compared to cases containing an extract obtained from a Bofu-tsusho-san crude drug formulation in which the amount of fresh ginger per 100 parts by weight was not 3 to 22 parts by weight.

[0042] [Table 3]

[0043] [Table 4]

[0044] [Table 5]

[0045] [Table 6]

Claims

1. Bofu Tsusho San extract, Magnesium stearate and Silicate compounds and, Starch, lactose, hydroxypropyl cellulose, and crystalline cellulose, and A tablet composition comprising, A tablet composition wherein the crude drug preparation used to extract the Bofu-tsusho-san extract contains 3 to 22 parts by weight of fresh ginger per 100 parts by weight of the crude drug preparation.

2. The tablet composition according to claim 1, comprising 65% by weight or more of the Bofu-tsusho-san extract.

3. A tablet comprising the tablet composition according to claim 1 or 2.

4. The tablet according to claim 3, which is a plain tablet.

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