JP7618484B2 - Tablet Composition - Google Patents

Description

The present invention relates to an extract preparation of Eppikajutsubuto.

Eppikajutsubuto is a Kampo medicine made by adding Bushi to Eppikajutsuto, and is used in cases of severe symptoms such as edema, chills, and difficulty urinating when symptoms are due to Eppikajutsuto. Eppikajutsubuto was added to the approval standards for general-use Kampo preparations relatively recently (Non-Patent Document 1).

Eppikajutsuto contains 6g of Ephedra, 8g of Sekko, 3g of Ginger, and 2g of Licorice.
It is commercially available as a herbal medicine mixture consisting of 4 g of Atractylodes Root, 3 g of Taiso, and 1 g of Bushi, and is taken by decoction (Non-patent Document 2).

Approval Standards for General Kampo Preparations, Reference Material 2-2, Ministry of Health, Labor and Welfare, Pharmaceuticals and Food Safety Bureau, April 15, 2011 Eppikajutsubuto Easy decoction 5-day supply (15 packets) Swelling Eczema Arthritis Pharmacy preparation, [online], Akao Kampo Pharmacy, [Searched on March 20, 2021], Internet <URL: https://store.shopping.yahoo.co.jp/akaokanpou/eppikajutu-kpc5.html>

Currently, Eppikajutsubuto can only be taken by decoction of a mixture of herbs that is commercially available, and there is no extract preparation. Furthermore, the pharmaceutical properties of an Eppikajutsubuto extract preparation have not yet been investigated.

The object of the present invention is to provide an Eppikajutsubuto extract preparation with excellent formulation properties.

After extensive research, the inventors have found that tablets with excellent hardness can be produced by tableting Ekpi-ka-jutsu-to extract. Moreover, the hardness of Ekpi-ka-jutsu-to extract tablets is improved compared to Ekpi-ka-jutsu-to extract, which has the same herbal composition except for the presence or absence of 'bushi', and this effect of improving hardness was unexpected in light of the fact that no technical relationship is known between 'bushi' and tablet hardness. Furthermore, the inventors have unexpectedly found that in the herbal preparation used to extract Ekpi-ka-jutsu-to extract, by further increasing the amount of 'bushi' relative to 'ginger', it may be possible to further improve hardness and disintegration. The present invention was completed based on these findings and through further research.

That is, the present invention provides the following aspects.
Item 1. A tablet composition containing an extract of Eppikajutsubuto.
Item 2. The tablet composition according to Item 1, wherein the herbal medicine mixture used for extracting the Eppikajutsufuto extract contains 0.3 to 1 part by weight of Bupleurum per part by weight of Zingiber officinale.
Item 3. The tablet composition according to item 1, wherein the herbal medicine mixture used for extracting the Eppikajutsufuto extract contains 0.7 to 1 part by weight of Bupleurum per 1 part by weight of Zingiber officinale.
Item 4. The tablet composition according to any one of Items 1 to 3, comprising 60 to 95% by weight of the Eppikajutsubuto extract.
Item 5. The tablet composition according to any one of Items 1 to 4, comprising 5 to 40% by weight of a disintegrant.
Item 6. The tablet composition according to Item 5, wherein the disintegrant is light anhydrous silicic acid, carmellose calcium, and/or starch.

The present invention provides Eppikajutsubuto extract tablets with excellent hardness.

The tablet composition of the present invention is characterized by containing Eppikajutsufuto extract. The tablet composition of the present invention is described in detail below.

The herbal medicines that make up Eppikajutsubuto are Ephedra, Sekko, Atractylodes Root, Bushi, Zingiber officinale, Glycyrrhiza Root, and Taiso. As the Atractylodes Root, Byaku-Atractylodes Root and/or Sou-Atractylodes Root can be used, and from the viewpoint of further improving the tablet hardness or from the viewpoint of improving disintegrability as well as said viewpoint, Sou-Atractylodes Root is preferably used. As the Bushi, Bushi powder and/or processed Bushi can be used, and from the viewpoint of further improving the tablet hardness or from the viewpoint of improving disintegrability as well as said viewpoint, processed Bushi is preferably used.

The amount of each herb in the herbal preparation used in the production of the Eppikajutsufuto extract used in the present invention is not particularly limited, but the content of Bushi per part by weight of Zingiber officinale is, for example, 0.3 to 1 part by weight, and from the viewpoint of further improving tablet hardness, preferably 0.6 to 1 part by weight. Furthermore, from the viewpoint of further improving tablet hardness and disintegration, more preferably 0.7 to 1 part by weight, even more preferably 0.8 to 1 part by weight, even more preferably 0.9 to 1 part by weight, and even more preferably 0.95 to 1 part by weight.

Specific compositions of the herbal preparations used in the manufacture of the Eppikajutsubuto extract used in the present invention include, for example, 4 to 6 parts by weight of Ephedra, 8 to 10 parts by weight of Gypsum, 3 to 4 parts by weight of Atractylodes orthositae, 0.3 to 1 part by weight of Scutellaria baicalensis, 1 part by weight of Zingiber officinale, 1.5 to 2 parts by weight of Licorice Root, and 3 to 4 parts by weight of Atractylodes orthositae; from the viewpoint of further improving tablet hardness, or from the viewpoint of improving disintegrability as well as the tablet hardness, preferably, 5 to 6 parts by weight of Ephedra, 8 to 9 parts by weight of Gypsum, 3.5 to 4 parts by weight of Atractylodes orthositae, 0.6 to 1 part by weight of Scutellaria baicalensis, 1 part by weight of Zingiber officinale, 1.8 to 2 parts by weight of Licorice Root, and 3 to 3.5 parts by weight of Atractylodes orthositae; from the viewpoint of further improving tablet hardness, preferably, 5 to 6 parts by weight of Ephedra, 8 to 9 parts by weight of Gypsum, 3.5 to 4 parts by weight of Atractylodes orthositae, 0.6 to 1 part by weight of Scutellaria baicalensis, 1 part by weight of Zingiber officinale, 1.8 to 2 parts by weight of Licorice Root, and 3 to 3.5 parts by weight of Atractylodes orthositae; From the viewpoint of further improving tablet hardness and disintegrability, more preferred are 5 to 6 parts by weight of Ephedra, 8 to 9 parts by weight of Gypsum, 3.5 to 4 parts by weight of Atractylodes orbiculatus, 0.7 to 1 part by weight of Atractylodes orbiculatus, 1 part by weight of Zingiber officinale, 1.8 to 2 parts by weight of Licorice Root, and 3 to 3.5 parts by weight of Atractylodes orbiculatus; from the viewpoint of further improving tablet hardness and disintegrability, even more preferred are 6 parts by weight of Ephedra, 8 parts by weight of Gypsum, 4 parts by weight of Atractylodes orbiculatus, 0.8 to 1 part by weight of Atractylodes orbiculatus (more preferably 0.9 to 1 part by weight, even more preferably 0.95 to 1 part by weight, and particularly preferably 1 part by weight), 1 part by weight of Zingiber officinale, 2 parts by weight of Licorice Root, and 3 parts by weight of Atractylodes orbiculatus.

The Eppikajutsubuto extract used in the present invention can be obtained by extracting the herbal preparation by a known method. For example, the method of extracting the herbal preparation includes adding water in an amount of about 10 to 20 times, preferably 13 to 18 times, the amount of the herbal preparation, and stirring at about 80 to 100°C, preferably 95 to 100°C, for about 0.5 to 3 hours, preferably 0.5 to 1.5 hours for extraction. After extraction, the solid matter is removed by solid-liquid separation such as centrifugation or filtration, and if necessary, by subjecting it to concentration or drying treatment, the Eppikajutsubuto extract can be obtained.

To obtain Eppikajutsubuto extract in the form of extract powder, the extract from which the solids have been removed may be concentrated as necessary and then subjected to a drying process such as spray drying, reduced pressure concentration drying, or freeze drying. In addition, when subjecting the extract to a drying process (especially spray drying), an excipient may be added to the extract as necessary.

The content of the Eppikajutsubuto extract in the tablet composition of the present invention is not particularly limited, but may be 60 to 95% by weight. The Eppikajutsubuto extract itself in the tablet composition of the present invention is obtained from a herbal preparation containing Busi, and serves to improve tablet hardness. Therefore, unlike typical herbal extract tablets, the tablet composition of the present invention can have high hardness even if the content of the Eppikajutsubuto extract itself is high. Therefore, suitable examples of the Eppikajutsubuto extract in the tablet composition of the present invention include 70 to 95% by weight, more preferably 72 to 95% by weight, even more preferably 74 to 95% by weight, even more preferably 76 to 95% by weight, and even more preferably 78 to 95% by weight.

Other Ingredients The tablet composition of the present invention may contain additives and/or bases as ingredients other than the Eppii Ka Sutsubu To extract, as long as the effects of the present invention are not impaired.

The additives and bases are not particularly limited as long as they are pharma- ceutically acceptable, but examples thereof include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV protection agents, preservatives, flavorings, fragrances, powders, thickeners, dyes, and chelating agents. These additives may be used alone or in combination of two or more. The content of these additives and bases is appropriately set according to the type of additives and bases used, as long as they can be molded into tablets.

Among these additives and bases, preferred are disintegrants (e.g., light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, carmellose, carmellose sodium, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropylcellulose, low-substituted carboxymethyl starch, crystalline cellulose, starch, sodium starch glycolate, crospovidone, etc.), magnesium stearate, calcium stearate, calcium silicate, magnesium silicate, synthetic hydrotalcite, etc. Of these, from the viewpoint of further improving tablet hardness, or from the viewpoint of improving disintegrability in addition to the above, more preferred are light anhydrous silicic acid, carmellose calcium, starch, and magnesium stearate.

The tablet composition of the present invention can form tablets with high hardness without impairing disintegrability, and therefore can effectively form tablets with high hardness even with a small amount of disintegrant used. From this viewpoint, a suitable amount of disintegrant used is, for example, 5 to 40% by weight, preferably 5 to 30% by weight, more preferably 5 to 25% by weight, and even more preferably 5 to 20% by weight. From the viewpoint of achieving both excellent hardness and disintegrability, a more suitable amount of disintegrant used is, for example, 10 to 20% by weight, even more preferably 15 to 20% by weight, and particularly preferably 17 to 20% by weight.

Furthermore, when light anhydrous silicic acid, carmellose calcium, and starch are used as disintegrants in the tablet composition of the present invention, the blending weight ratio of these (light anhydrous silicic acid:carmellose calcium:starch) is preferably [1-3]:[0.6-1]:1, more preferably [1.5-2.5]:[0.7-0.9]:1, and even more preferably [1.8-2.2]:[0.75-0.85]:1, from the viewpoint of obtaining excellent hardness and/or disintegrability.

In addition, the tablet composition of the present invention may contain other nutritional components and pharmacological components as necessary in addition to the Eppikajutsufuto extract. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedatives, hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, and menthols. These nutritional components and pharmacological components may be used alone or in combination. The content of these components is appropriately set depending on the type of components used.

Formulation The tablet composition of the present invention is formed into a tablet. The shape and size of the tablet are not particularly limited. Examples of tablet shapes include round, oval, triangular, and rectangular. In the case of round tablets, the diameter is 6 to 12 mm, preferably 8 to 10 mm. The weight per tablet is 200 to 600 mg, preferably 300 to 400 mg.

The tablets produced from the tablet composition of the present invention may be plain tablets (bare tablets) or coated tablets with a coating applied to the surface for the purpose of stabilizing the drug and masking the taste and odor. Examples of coated tablets include sugar-coated tablets and film-coated tablets (stomach-soluble tablets, enteric-coated tablets) coated with a film containing a water-soluble, enteric-soluble or gastrosoluble polymer base. The tablet composition of the present invention has excellent tablet hardness, so that even plain tablets are physically stable. The hardness of plain tablets produced from the tablet composition of the present invention is 180N or more, preferably 185N or more, more preferably 200N or more, even more preferably 210N or more, even more preferably 220N or more, even more preferably 230N or more, and particularly preferably 235N or more. The upper limit of the hardness is not particularly limited, and examples thereof include 250N or less, 245N or less, or 240N or less.

Manufacturing method The tablet composition of the present invention can be manufactured according to a conventional formulation method adopted in the pharmaceutical field using the Eppikajutsufuto extract, and additives, base materials, and pharmacological ingredients added as necessary. Preferably, the manufacturing method of the tablet composition of the present invention includes a granulation step of granulating the Eppikajutsufuto extract or the Eppikajutsufuto extract mixture mixed with additives, base materials, other nutritional ingredients, and/or other pharmacological ingredients as necessary, and a tableting step of tableting the granulated product. The tableting pressure in the tableting step is, for example, 4 to 20 kN, preferably 6 to 20 kN, more preferably 8 to 15 kN. Since the tablet composition of the present invention has excellent tablet hardness, a tablet with high hardness can be effectively formed even with a relatively small tableting pressure. From this viewpoint, a suitable example of the tableting pressure in the tableting step is 8 to 13 kN, more preferably 8 to 11 kN, and even more preferably 8 to 10 kN.

Uses The tablet composition of the present invention is used for applications in which it is formed into tablets, and furthermore, tablets produced from the tablet composition of the present invention may be used for any application in which the efficacy of Eppikajutsufuto extract is expected.

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

Test Example
1. Manufacturing of Eppikajutsuto Extract Powder A herbal preparation with the composition shown in Table 1 (processed bush was used as bush in the table) was used as the raw herbal medicine, and extracted with 15 times the weight of normal water at about 100°C for 1 hour, followed by hot solid-liquid separation and filtration to obtain an extract. The extract was concentrated under reduced pressure and dried using a spray dryer to obtain Eppikajutsuto Extract Powder (Eppikajutsuto Extract Powder for Comparative Example 1). The drying using the spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

2. Production of tablet composition The Eppikajutsubuto extract powder obtained in 1 above was mixed with the ingredients shown in Table 2 in the composition shown in the table, granulated, and compressed with a pressure of 9 kN to prepare tablets (plain tablets, weight 360 mg, diameter 9.5 mm).

3. Hardness and disintegration The hardness (N) of the manufactured tablets (plain tablets) was measured using a load cell type tablet hardness tester (breaking speed 0.5 mm/min), and disintegration (min) was evaluated according to the disintegration test method described in the Japanese Pharmacopoeia (17th edition). The disintegration time was the average value of three tablets. The results are shown in Table 2.

As is clear from Table 2, tablets containing Eppikajutsubuto extract showed improved hardness (Examples 1 to 3). In particular, when the weight ratio of Bushi to Ginger in the herbal mixture used to manufacture Eppikajutsubuto extract was set to a specified ratio or higher, improved hardness and disintegration properties were observed (Examples 1 and 2), demonstrating that the tablets had particularly excellent tablet properties.

Claims (6)

A tablet composition containing Eppikajutsubutou extract. The tablet composition according to claim 1, wherein the herbal medicine mixture used to extract the Eppikajutsufuto extract contains 0.3 to 1 part by weight of Bushi per part by weight of Zingiber officinale. The tablet composition according to claim 1, wherein the herbal medicine mixture used to extract the Eppikajutsufuto extract contains 0.7 to 1 part by weight of Bushi per part by weight of Zingiber officinale. The tablet composition according to any one of claims 1 to 3, containing 60 to 95% by weight of the Eppikajutsufuto extract. The tablet composition according to any one of claims 1 to 4, comprising 5 to 40% by weight of a disintegrant. The tablet composition according to claim 5, wherein the disintegrant is light anhydrous silicic acid, calcium carmellose, and/or starch.