tablet

Abstract

To provide a tablet containing isoflavones that achieves both hardness and compressibility. [Solution] The tablets of the present invention contain (A) isoflavones, (B) excipients, and (C) lubricants. It is preferable that (A) isoflavones contain daidzein and genistein. It is also preferable that the mass ratio of daidzein to genistein is genistein:daidzein = 1:0.5 to 4.5. Furthermore, it is also preferable that the tablets contain (D) a fluidizing agent.

Description

Technical Field

[0001] The present invention relates to tablets containing isoflavones.

Background Art

[0002] In recent years, various health foods have been developed based on the increasing interest in health, and research has been conducted on various materials used in health foods. Isoflavone, a flavonoid contained in beans and the like, has a structure similar to estradiol, a type of female hormone, and has anti-estrogenic and estrogen-like effects. Epidemiological studies and intervention studies on soy isoflavones so far have suggested the preventive effect of hormone-dependent cancers such as breast cancer and prostate cancer due to the anti-estrogenic effect, and the improvement effect of menopausal disorders, postmenopausal osteoporosis, and hyperlipidemia due to the estrogen-like effect (Patent Documents 1 and 2).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] Tablets are one of the common dosage forms of health foods; however, there is a problem that isoflavones are not very suitable as raw materials for formulating tablets. Specifically, since isoflavones do not have excellent tableting suitability, when isoflavones are formulated into tablets together with excipients, it is likely to cause tableting problems such as deterioration of punch release. In addition, when isoflavones are formulated, the hardness of the tablets tends to be difficult to increase. If the pressure is increased to forcibly increase the hardness, it may cause deterioration of punch release.

Means for Solving the Problems

[0005] The inventors, while researching tablets containing isoflavones, discovered that by combining isoflavones with excipients and lubricants, it is possible to achieve both tablet hardness and compressibility, thus completing the present invention. In other words, the present invention provides tablets containing (A) isoflavones, (B) excipients and (C) lubricants. [Effects of the Invention]

[0006] The present invention provides a tablet containing isoflavones that achieves both hardness and compressibility. [Modes for carrying out the invention]

[0007] The present invention will be described below based on its preferred embodiments. In this specification, "tablet" means a compression-molded solid dosage form containing (A) isoflavones together with (B) excipients and (C) lubricants. Tablets can be prepared by compression of a mixture. In the present invention, "tablet" includes uncoated tablets, orally disintegrating tablets, and film-coated tablets.

[0008] The tablets of the present invention contain (A) isoflavones, (B) excipients, and (C) lubricants.

[0009] (A) Isoflavones

[0010] Isoflavones are a type of polyphenol, specifically flavonoids with isoflavone (3-phenylchromone) as their basic structure. Isoflavones are known to be abundant in leguminous plants, including soybeans and kudzu flowers.

[0011] Isoflavones contained in soybeans include non-glycosides (aglycones) such as daidzein, genistein, and glycitein, as well as their glycosides, acetylated glycosides, and malonylated glycosides. Examples of the aforementioned glycosides include daidzin, genistin, and glycitin. Examples of the aforementioned acetylated glycosides include acetylgenistin, acetyldaidzin, and acetylglycitin. Examples of malonylated soy isoflavone glycosides include malonylgenistin, malonyldaidzin, and malonylglycitin.

[0012] Furthermore, isoflavones contained in kudzu flowers include tectorigenin, a non-glycoside (aglycone), and tectorigenin-7-O-xylosyl glucoside and tectoridin, which are glycosides.

[0013] In the present invention, it is preferable to use isoflavones derived from soybeans as the isoflavone, as this can enhance the health and beauty benefits associated with soybean-derived isoflavones.

[0014] Furthermore, the fact that the agent of the present invention contains isoflavones that are non-glycosides (aglycones) is preferable because it is a material that is difficult to balance hardness, tabletability, and disintegration, thus excelling in the technical significance of the present invention. Moreover, using isoflavones that are non-glycosides (aglycones), which are in a form that can be absorbed in the intestines, makes it easier to reliably utilize isoflavones in the body, and thus makes it easier to further enhance the health and beauty effects attributed to isoflavones, which is also preferable.

[0015] The agent of the present invention preferably contains one or more isoflavones selected from daidzein, genistein, and glycitein, as this material is difficult to balance with hardness, tabletability, and disintegration, and is therefore superior in terms of the technical significance of the present invention. In particular, it is preferable to contain one or more isoflavones selected from daidzein and genistein, and among these, it is especially preferable to contain daidzein and genistein, which is superior in terms of the technical significance of the present invention. Furthermore, genistein is known to have estrogen-like effects. Daidzein is metabolized in the intestines to equol, an estrogen-like structure. Due to these estrogen-like effects, these isoflavones are known to alleviate menopausal symptoms and suppress the deterioration of tissues such as bones, skin, blood vessels, and hair, and to maintain their function. Therefore, by containing genistein and daidzein in the agent of the present invention, the estrogen-like effects of these components can be effectively exerted. In particular, the agent of the present invention is preferable in that it contains daidzein, genistein, and glycitein, as this excels in the technical significance of the present invention.

[0016] In the isoflavones used in the present invention, when daidzein and genistein are used in combination, the composition ratio is not particularly limited, and they can be used in suitable combinations. However, in order to exhibit their health effects and to have excellent disintegration properties, the mass ratio of daidzein to genistein is preferably genistein:daidzein = 1:0.5 to 4.5, more preferably 1:0.5 to 4.0, even more preferably 1:0.5 to 3.5, even more preferably 1:0.6 to 3.0, and even more preferably 1:0.7 to 2.5.

[0017] Furthermore, when daidzein and / or genistein are used in combination with glycitein, the preferred mass ratio of glycitein / daidzein is 0.001 or more and / or 10 or less, particularly 0.01 or more and / or 5 or less, and the preferred mass ratio of glycitein / genistein is 0.001 or more and / or 10 or less, particularly 0.01 or more and / or 5 or less. Furthermore, in addition to exhibiting its health benefits, it exhibits excellent disintegration properties, so the ratio of the mass of glycitein to the total amount of daidzein and genistein is more preferably 0.01 to 2.0, even more preferably 0.02 to 1.0, even more preferably 0.03 to 0.6, even more preferably 0.04 to 0.3, and even more preferably 0.05 to 0.2.

[0018] The proportion of isoflavones in the tablets of the present invention is not particularly limited, but from the viewpoint of better exhibiting the health effects of isoflavones, it is preferable to include 0.1% by mass or more, more preferably 1% by mass or more, even more preferably 1.5% by mass or more, and particularly preferably 2% by mass or more.

[0019] The proportion of isoflavones in the tablets of the present invention is not particularly limited, but from the viewpoint of ensuring sufficient excipient volume to easily achieve both hardness and tabletability, and from the viewpoint of improving disintegration, it is preferable to include them in an amount of 30% by mass or less, more preferably 20% by mass or less, even more preferably 15% by mass or less, and particularly preferably 10% by mass or less.

[0020] In the isoflavones used in this invention, in addition to exhibiting health benefits, from the viewpoint of balancing hardness and tablet properties, the total amount of daidzein, genistein, and glycysteine ​​in relation to the total amount of isoflavones is preferably 1% by mass or more, more preferably 10% by mass or more, more preferably 25% by mass or more, even more preferably 50% by mass or more, even more preferably 60% by mass or more, and most preferably 80% by mass or more. In the isoflavones used in the present invention, in addition to exerting health effects, from the perspective of the balance of hardness and tableting properties, the proportion of daidzein in the total amount of isoflavones is preferably blended in an amount of 0.1% by mass or more, preferably 1% by mass or more, more preferably 10% by mass or more, still more preferably 20% by mass or more, still more preferably 30% by mass or more, and most preferably 35% by mass or more. Further, the proportion of daidzein in the total amount of isoflavones is preferably blended in an amount of 97% by mass or less, more preferably 90% by mass or less, still more preferably 80% by mass or less, still more preferably 70% by mass or less, and particularly preferably 60% by mass or less. The proportion of genistein in the total amount of isoflavones is preferably blended in an amount of 0.1% by mass or more, preferably 1% by mass or more, more preferably 10% by mass or more, still more preferably 20% by mass or more, still more preferably 30% by mass or more, and most preferably 35% by mass or more. Further, the proportion of genistein in the total amount of isoflavones is preferably blended in an amount of 97% by mass or less, more preferably 90% by mass or less, still more preferably 80% by mass or less, still more preferably 70% by mass or less, and particularly preferably 60% by mass or less. The proportion of glycitein in the total amount of isoflavones is preferably blended in an amount of 0.1% by mass or more, preferably 0.5% by mass or more, more preferably 1% by mass or more, still more preferably 3% by mass or more, and still more preferably 5% by mass or more. Further, the proportion of genistein in the total amount of isoflavones is preferably blended in an amount of 97% by mass or less, more preferably 90% by mass or less, still more preferably 80% by mass or less, still more preferably 40% by mass or less, and particularly preferably 20% by mass or less.

[0021] When the tablet of the present invention contains daidzein, its blending ratio is not particularly limited, but preferably in the tablet, it is 0.3% by mass or more, more preferably 1% by mass or more, still more preferably 2% by mass or more, preferably 20% by mass or less, more preferably 10% by mass or less, and still more preferably 8% by mass or less.

[0022] When the tablet of the present invention contains genistein, its blending ratio is not particularly limited, but preferably it is 0.3% by mass or more, more preferably 1% by mass or more, still more preferably 2% by mass or more, preferably 20% by mass or less, more preferably 10% by mass or less, and still more preferably 8% by mass or less in the tablet.

[0023] When the tablet of the present invention contains glycysteine, its blending ratio is not particularly limited, but preferably it is 0.01% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.7% by mass or more, preferably 12% by mass or less, more preferably 8% by mass or less, and still more preferably 4% by mass or less in the tablet.

[0024] (B) Excipient The tablet of the present invention contains (B) an excipient. Examples of the excipient include cellulose, cellulose derivatives, saccharides, starch and its derivatives, dextrin, and the like.

[0025] Examples of cellulose include powdered cellulose and crystalline cellulose. Crystalline cellulose is obtained by partially depolymerizing α-cellulose obtained as pulp from fibrous plants with an acid and then purifying it. For example, it corresponds to the crystalline cellulose described in the Explanation Book of the Fifteenth Revised Japanese Pharmacopoeia (published by Hirokawa Shoten). Crystalline cellulose can be classified into crystalline cellulose powder and crystalline cellulose complex. Powdered cellulose is obtained by treating α-cellulose obtained as pulp from fibrous plants, then purifying it, and mechanically pulverizing it. For example, it corresponds to the powdered cellulose described in the Explanation Book of the Fifteenth Revised Japanese Pharmacopoeia (published by Hirokawa Shoten). From the viewpoint of achieving both tableting properties and hardness, it is particularly preferable to use crystalline cellulose as the cellulose.

[0026] Examples of cellulose derivatives include derivatives chemically modified with a carboxymethyl group, hydroxypropyl group, methoxy group, etc. to enhance water solubility, such as carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and methyl cellulose. In particular, from the viewpoint of achieving both tablet compressibility and hardness, nonionic cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose, and methylcellulose are preferred, and hydroxypropylcellulose is especially preferred.

[0027] Examples of sugars include sugar alcohols, monosaccharides, disaccharides, and oligosaccharides.

[0028] Sugar alcohols include monosaccharide alcohols, disaccharide alcohols, and alcohols of three or more sugars. Examples of monosaccharide alcohols include tetritos such as erythritol, D-threitol, and L-threitol; pentitols such as D-arabinitol and xylitol; hexitols such as D-iditol, galactitol (dalcitol), and D-glucitol (sorbitol); cyclitols such as inositol; mannitol, boremitol, ribitol, perseitol, and D-erythro-D-galacto-octitol. Examples of disaccharide alcohols include reduced maltose (maltitol), lactitol, and reduced palatinose (isomalto). Examples of alcohols of three or more sugars include maltotriitol, isomalttriitol, and panitol.

[0029] Examples of monosaccharides include glucose, galactose, fructose, and mannose. Examples of disaccharides include sucrose, maltose, lactose, trehalose, turanose, and cellobiose. Examples of oligosaccharides include those with three to twenty sugars, preferably those with three to ten sugars, and more preferably those with three to six sugars.

[0030] Among sugars, sugar alcohols are preferred, disaccharide alcohols are more preferred, and reduced maltose is particularly preferred.

[0031] When the tablets of the present invention contain reduced maltose, from the viewpoint of achieving both tabletability and hardness, the proportion of reduced maltose in the sugars is preferably 35% by mass or more, more preferably 40% by mass or more, even more preferably 50% by mass or more, and even more preferably 60% by mass or more.

[0032] Natural starch is one example of starch. Sources of starch include corn, potato, kudzu, tapioca, sweet potato, rice, wheat, barley, yam, and taro.

[0033] Examples of starch derivatives include modified starch, oxidized starch, enzyme-treated starch, pregelatinized starch, starch phosphate, distarch phosphate, starch acetate, starch octenyl succinate, glycerol distarch, carboxymethyl starch, hydroxypropyl starch, crosslinked starch, soluble starch, grafted starch, and sodium carboxymethyl starch.

[0034] As for the dextrin, one with a DE of 4 or higher is preferred, one with a DE of 6 or higher is more preferred, and one with a DE of 8 or higher is particularly preferred. Furthermore, one with a DE of 15 or lower is preferred, and one with a DE of 10 or lower is more preferred.

[0035] From the viewpoint of balancing hardness and tabletability, the tablets of the present invention preferably contain, in particular, one or more excipients selected from cellulose, sugar alcohols, and cellulose derivatives, and especially preferably contain one or more selected from cellulose, reduced maltose, and cellulose derivatives, and most preferably contain at least one selected from cellulose, reduced maltose, and hydroxypropylcellulose.

[0036] From the viewpoint of balancing the hardness, disintegration, and tabletability of the tablet, the content of (B) excipient in the tablet of the present invention is preferably 5% by mass or more, more preferably 20% by mass or more, preferably 40% by mass or more, particularly preferably 50% by mass or more, and particularly preferably 55% by mass or more.

[0037] From the viewpoint of balancing the hardness, disintegration, and tabletability of the tablet, the content of (B) excipient in the tablet of the present invention is preferably 99% by mass or less, more preferably 97% by mass or less, even more preferably 95% by mass or less, and particularly preferably 90% by mass or less.

[0038] Furthermore, from the viewpoint of balancing the hardness, disintegration, and tabletability of the tablet, the ratio of the mass of (B) excipient to the mass of (A) isoflavone in the tablet of the present invention ((B) / (A)) is preferably 0.01 or more, more preferably 1 or more, even more preferably 3 or more, and even more preferably 8 or more. Also, the above ratio ((B) / (A)) is preferably 200 or less, more preferably 120 or less, even more preferably 80 or less, and even more preferably 40 or less.

[0039] When the tablets of the present invention contain sugar alcohols, from the viewpoint of balancing disintegration, hardness, and tabletability, the amount is preferably 30% by mass or more, more preferably 45% by mass or more, even more preferably 50% by mass or more, and particularly preferably 60% by mass or more. In particular, the amount of reduced maltose is preferably above the lower limit mentioned above, that is, 30% by mass or more, more preferably 45% by mass or more, even more preferably 50% by mass or more, and particularly preferably 60% by mass or more.

[0040] Furthermore, if the tablets of the present invention contain sugar alcohols, from the viewpoint of balancing hardness, disintegration, and tabletability, the amount is preferably 95% by mass or less, more preferably 90% by mass or less, and particularly preferably 85% by mass or less. In particular, the amount of reduced maltose is less than or equal to the above upper limit, that is, 95% by mass or less is preferred, more preferably 90% by mass or less, and particularly preferably 85% by mass or less.

[0041] The tablets of the present invention can be made to have even greater hardness if they contain a cellulose derivative. When the tablets of the present invention contain a cellulose derivative, the amount is preferably 0.1% by mass or more, more preferably 1% by mass or more, and even more preferably 2% by mass or more. In the tablets of the present invention, the content of the cellulose derivative may be 25% by mass or less, 20% by mass or less, 14% by mass or less, 12% by mass or less, 10% by mass or less, or 6% by mass or less.

[0042] The tablets of the present invention can be made to have even greater hardness if they contain cellulose. When the tablets of the present invention contain cellulose, the amount is preferably 0.1% by mass or more, more preferably 1% by mass or more, and even more preferably 2% by mass or more. In the tablets of the present invention, if cellulose is included, from the viewpoint of balancing hardness and tabletability, the content of cellulose in the tablet is preferably 95% by mass or less, more preferably 90% by mass or less, and even more preferably 88% by mass or less.

[0043] The tablets of the present invention are preferable in that a high total proportion of cellulose and sugars in the excipient enhances their disintegration properties. From this viewpoint, the total proportion of cellulose and sugars in the excipient is preferably 70% by mass or more, more preferably 80% by mass or more, and particularly preferably 85% by mass or more.

[0044] (C) Lubricant The tablets of the present invention contain a (C) lubricant. A (C) lubricant is a substance added to a dosage form such as a tablet or granule after it has been compressed, in order to reduce friction or wear and thus allow it to separate from the mold or die. The present invention, by using a (C) lubricant, not only improves tablet compressibility but also improves the hardness of the tablets. Examples of (C) lubricants include metal stearate salts; stearic acid; high melting point waxes; and water-soluble lubricants, such as sodium oleate and polyethylene glycol. Examples of metal stearate salts include alkali metal salts and alkaline earth metal salts of stearic acid, such as magnesium stearate, calcium stearate, and potassium stearate. In particular, as a (C) lubricant, metal stearate salts are especially preferred, magnesium stearate or calcium stearate are more preferred, and calcium stearate is especially preferred, due to their excellent effects as described above.

[0045] (C) The amount of lubricant in the tablet is preferably 0.1% by mass or more, more preferably 0.2% by mass or more, even more preferably 0.4% by mass or more, even more preferably 0.6% by mass or more, particularly preferably 0.8% by mass or more, especially preferably 1.0% by mass or more, and most preferably 1.2% by mass or more, from the viewpoint of making it easier for the above-mentioned effects of (C) lubricant to be exerted. Furthermore, in order to facilitate the exertion of the above-mentioned effects, the content of (C) lubricant in the tablet is preferably 5% by mass or less, more preferably 4% by mass or less, even more preferably 3% by mass or less, even more preferably 2.7% by mass or less, particularly preferably 2.6% by mass or less, and especially preferably 2.5% by mass or less.

[0046] Furthermore, from the viewpoint of balancing the hardness and compressibility of the tablets, the ratio of the mass of (C) lubricant to the mass of (A) isoflavone in the tablets of the present invention ((C) / (A)) is preferably 0.001 or more, more preferably 0.005 or more, more preferably 0.01 or more, and even more preferably 0.02 or more. Also, the above ratio ((C) / (A)) is preferably 20 or less, more preferably 10 or less, more preferably 5 or less, and even more preferably 2 or less.

[0047] Other ingredients Furthermore, the tablets of the present invention preferably contain (D) a fluidizing agent. (D) A fluidizing agent is an agent added to prevent the powder from clumping together during tableting and to improve fluidity. By containing (D) a fluidizing agent, the tablets of the present invention can have their hardness further increased.

[0048] (D) Examples of fluidizing agents include silicon dioxide and magnesium aluminometasilicate. Examples of silicon dioxide include light anhydrous silicic acid, heavy anhydrous silicic acid, and hydrated silicon dioxide. In the tablets of the present invention, silicon dioxide is particularly preferred as the fluidizing agent (D) because it is easier to further increase the hardness.

[0049] (D) If a fluidizing agent is included, from the viewpoint of balancing hardness and tabletability, the amount of (D) fluidizing agent in the tablet is preferably 0.1% by mass or more, more preferably 0.2% by mass or more, even more preferably 0.4% by mass or more, even more preferably 0.6% by mass or more, and most preferably 1% by mass or more.

[0050] From the viewpoint of balancing hardness and tabletability, the amount of (D) fluidizer in the tablet is preferably 5% by mass or less, more preferably 3% by mass or less, even more preferably 2.8% by mass or less, even more preferably 2.7% by mass or less, and most preferably 2.5% by mass or less.

[0051] From the viewpoint of balancing the hardness and compressibility of the tablets, in the tablets of the present invention, the ratio of the mass of (D) fluidizer to the mass of (A) isoflavone ((D) / (A)) is preferably 0.001 or more, more preferably 0.01 or more, and even more preferably 0.1 or more. Furthermore, the above ratio ((D) / (A)) is preferably 10 or less, more preferably 4 or less, even more preferably 2 or less, and even more preferably 1 or less.

[0052] The tablets of the present invention preferably contain (E) vitamins, as this increases the hardness of the tablets and improves their disintegration properties. Furthermore, since vitamins are essential components for the body, it is preferable to include vitamins separately in addition to (A) isoflavones from the viewpoint of nutritional intake. As for the vitamins to be included, for example, a vitamin preparation containing vitamins in high purity (e.g., 80% by mass or more) may be used. Vitamins are a general term for organic compounds other than carbohydrates, proteins, and lipids that are essential nutrients for the survival and growth of living organisms but cannot be synthesized in sufficient quantities within the organism's body. They are classified into water-soluble vitamins and fat-soluble vitamins.

[0053] Examples of water-soluble vitamins include vitamins B and C. Vitamins belonging to the vitamin B group include vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxal, pyridoxine), vitamin B7 (biotin), vitamin B9 (folic acid), and vitamin B12 (cyanocobalamin). These vitamins may be the components in parentheses, or salts or derivatives of the components in parentheses. These may be used individually or in combination of two or more.

[0054] Examples of fat-soluble vitamins include vitamin A, vitamin D, vitamin E, and their salts and derivatives. These may be used individually or in combination of two or more.

[0055] Examples of derivatives include disulfide-modified and acylated compounds. Examples of salts include nitrates and hydrochlorides.

[0056] Examples of thiamine derivatives include bisthiamine, thiamine disulfide (TDS), thiamine dicetyl sulfate, benfotiamine (BTMP), prosultiamine (TPD), fursultiamine (TTFD), bisbentiamine (BTDS), sicotiamine (CCT), octotiamine (TATD), allithiamine, thiamine propyl disulfide, thiamine tetrahydrofurfuryl disulfide (TPFD), dicethiamine (DCET), bisbutiamine, bisibthiamine (DBT), thiamine monophosphate disulfide, thiamine pyrophosphate, sicotiamine, thiamine ethyl disulfide, and thiamine propyl disulfide. Examples of salts of thiamine and its derivatives include thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, dicethiamine hydrochloride, and fursultiamine hydrochloride.

[0057] Another example of a pyridoxine salt is pyridoxine hydrochloride.

[0058] When vitamins are used in the tablets of the present invention, it is preferable to use water-soluble vitamins from the viewpoint of balancing hardness, tabletability, and disintegration properties, and among these, at least one selected from vitamin B is preferred, and in particular, at least one selected from vitamin B1 and vitamin B6 is preferred.

[0059] When vitamins are used in the tablets of the present invention, from the viewpoint of balancing hardness, compressibility, and disintegration, the amount is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.4% by mass or more, even more preferably 0.6% by mass or more, particularly preferably 0.8% by mass or more, and most preferably 1% by mass or more.

[0060] Furthermore, in the tablets of the present invention, when vitamins are used, from the viewpoint of balancing hardness, compressibility, and disintegration, the amount is preferably 10% by mass or less, more preferably 8% by mass or less, even more preferably 5% by mass or less, even more preferably 4% by mass or less, and particularly preferably 3% by mass or less.

[0061] From the viewpoint of balancing the hardness, disintegration properties, and tabletability of the tablets, the ratio of the mass of (E) vitamins to the mass of (A) isoflavones in the tablets of the present invention ((E) / (A)) is preferably 0.005 or more, more preferably 0.007 or more, more preferably 0.01 or more, and even more preferably 0.05 or more. Furthermore, the above ratio ((E) / (A)) is preferably 15 or less, more preferably 8 or less, more preferably 2 or less, and even more preferably 0.5 or less.

[0062] When vitamin B1 is used in the tablets of the present invention, from the viewpoint of balancing hardness, compressibility, and disintegration, the amount is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.2% by mass or more, even more preferably 0.3% by mass or more, particularly preferably 0.4% by mass or more, especially preferably 0.5% by mass or more, most preferably 1.0% by mass or more, and most preferably 1.1% by mass or more.

[0063] When vitamin B1 is used in the tablets of the present invention, from the viewpoint of balancing hardness, compressibility, and disintegration, the amount is preferably 3% by mass or less, more preferably 2.9% by mass or less, even more preferably 2.8% by mass or less, even more preferably 2.7% by mass or less, particularly preferably 2.6% by mass or less, and especially preferably 2.5% by mass or less.

[0064] When vitamin B6 is used in the tablets of the present invention, from the viewpoint of balancing hardness, compressibility, and disintegration, the amount is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.2% by mass or more, even more preferably 0.3% by mass or more, particularly preferably 0.4% by mass or more, and particularly preferably 0.5% by mass or more.

[0065] When vitamin B6 is used in the tablets of the present invention, from the viewpoint of balancing hardness, compressibility, and disintegration, the amount is preferably 3% by mass or less, more preferably 2.9% by mass or less, even more preferably 2.8% by mass or less, even more preferably 2.7% by mass or less, particularly preferably 2.6% by mass or less, and especially preferably 2.5% by mass or less.

[0066] When vitamin B1 and B6 are used in combination in the tablets of the present invention, from the viewpoint of balancing hardness, tabletability, and disintegration, the ratio of vitamin B1:B6 is preferably 100:0.01 or higher, more preferably 100:0.1 or higher, even more preferably 100:1 or higher, particularly preferably 100:5 or higher, and most preferably 100:10 or higher. Furthermore, when vitamin B1 and B6 are used in combination, from the viewpoint of balancing hardness and tabletability, the ratio of vitamin B1:B6 is preferably 100:1000 or lower, more preferably 100:200 or lower, even more preferably 100:150 or lower, even more preferably 100:90 or lower, and most preferably 100:70 or lower.

[0067] The tablets of the present invention may contain 40% by mass or less, 20% by mass or less, 10% by mass or less, or 5% by mass or less of any component other than (A) isoflavones, (B) excipients, (C) lubricants, (D) fluidizers, and (E) vitamins.

[0068] • Dimensions, physical properties The tablets of the present invention preferably have a mass of 150 mg or more per tablet, and more preferably 200 mg or more, in order to easily achieve a balance of ease of swallowing, hardness, and tabletability. Furthermore, the tablets of the present invention preferably have a mass of 500 mg or less per tablet, more preferably 400 mg or more, even more preferably 300 mg or less, and most preferably 280 mg or less, in order to easily achieve a balance of ease of swallowing, hardness, and tabletability.

[0069] The tablets of the present invention preferably have a diameter of 5 mm or more, more preferably 5.5 mm or more, and most preferably 6 mm or more, from the viewpoint of easily achieving a balance between ease of swallowing, hardness, and compressibility. Similarly, from the viewpoint of easily achieving a balance between ease of swallowing, hardness, and compressibility, the diameter is preferably 12 mm or less, more preferably 11 mm or less, and particularly preferably 10 mm or less. Here, the diameter of the lock is, if the lock is not circular, the area-converted diameter based on the projected area when the lock is placed on a horizontal plane in such a way that the contact area is maximized, and projected from above in the vertical direction. Tablet shapes include round tablets, oval tablets, and flower-shaped tablets.

[0070] The tablets of the present invention preferably have a hardness of 6.7 kgf or more, more preferably 7.0 kgf or more, particularly preferably 7.5 kgf or more, even more preferably 8 kgf or more, and particularly preferably 8.9 kgf or more, as this allows for an easy balance between hardness and compressibility.

[0071] The tablets of the present invention preferably have a hardness of 21 kgf or less, more preferably 17 kgf or less, particularly preferably 15 kgf or less, and most preferably 12 kgf or less, as this allows for an easy balance between hardness and compressibility. Hardness can be measured by the method described in the examples.

[0072] Furthermore, the tablets of this embodiment preferably have a disintegration time of 60 minutes or less when used as a solvent, more preferably 40 minutes or less, even more preferably 35 minutes or less, and particularly preferably 30 minutes or less. The lower limit of the disintegration time is, for example, 1 minute or more, for ease of tablet manufacturing. Disintegration time refers to the time it takes for a sample in a solvent to disintegrate. The procedure for measuring the disintegration time follows the method described in item "6.09" "Disintegration Test Method" of the General Test Methods in the Seventeenth Edition of the Japanese Pharmacopoeia. When using tablets with a diameter of 3 to 15 mm, a thickness of 4 to 7 mm, and a mass of 150 to 500 mg, it is preferable to use the Toyama Sangyo Co., Ltd., model number: NT-400, as the disintegration tester.

[0073] <Procedure for measuring disintegration time> One tablet is placed in each of the six glass tubes of a disintegration tester. Each glass tube is open at both the top and bottom, and a stainless steel mesh with a mesh size of 1.8 mm to 2.2 mm is attached to the bottom of each glass tube. The glass tubes containing the tablets are placed in water at 37 ± 2°C, and the disintegration tester is activated. The glass tubes in the disintegration tester are observed, and when it is confirmed that the tablets are beginning to disintegrate, the glass tubes are lifted and the disintegration process is observed. This process is repeated until the tablets have completely disintegrated. The time from when the disintegration tester is activated until all six tablets have disintegrated is measured, and this measured time is defined as the disintegration time. The tablets are considered to have disintegrated when no tablet residue is found in the glass tube, or when any residue found is clearly a soft substance that does not retain its original shape.

[0074] ·Manufacturing method The following describes a preferred method for manufacturing the tablets of this embodiment. The method for producing tablets according to this embodiment preferably includes the steps of mixing a raw material powder containing (A) isoflavone, (B) an excipient, and (C) a lubricant, and compressing the resulting mixed powder into tablets. The preferred mass ratios and components of (A) isoflavones, (B) excipients, and (C) lubricants in the raw material powder are the same as those in the tablets described above.

[0075] The tablets may contain a nucleus or not. In the case of tablets containing a nucleus, a raw material powder containing any nucleus is compressed into tablets.

[0076] The raw material powder may be the mixture itself of (A) isoflavones, (B) excipients, (C) lubricants, and other powdered components as needed, or it may be a granulated powder obtained by granulating a mixture of a powdered gelling agent, a specific powdered excipient, and other powdered components as needed. As for the granulation method, any known granulation method used when manufacturing oral tablets by granulation compression can be used without any particular limitations.

[0077] The tablets of the present invention may be for chewing, that is, tablets that are chewed in the mouth; they may be for swallowing, tablets that are washed down with water or the like and swallowed; they may be for gargling; or they may be tablets that are licked in the mouth and gradually dissolved, specifically lozenges. The tablets of the present invention are particularly preferable to be used for swallowing due to their excellent hardness. Furthermore, the tablets of this embodiment are for oral use, i.e., internal administration. The tablets of this embodiment can be used as a food composition or pharmaceutical composition (such as a pharmaceutical or quasi-drug), and can be used as a supplement, health food, nutritional functional food, functional food, food for specified health uses, and pharmaceutical.

[0078] • Preferred embodiments of the present invention Preferred embodiments of the present invention include, for example, the following: [1] A tablet containing (A) isoflavones, (B) excipients, and (C) lubricants. [2] (A) The tablet according to [1], wherein the isoflavone contains daidzein and genistein. [3] The tablet according to [1] or [2], characterized in that the mass ratio of daidzein to genistein is genistein:daidzein = 1:0.5 to 4.5. [4] Furthermore, a tablet according to any one of items [1] to [3], which contains (D) a fluidizing agent. [5] (A) A tablet according to any one of items [1] to [4], wherein the isoflavone content is 0.1 to 30% by mass, preferably 1 to 10% by mass. [6] (B) A tablet according to any one of items [1] to [5], wherein the excipient comprises cellulose, maltitol, or hydroxypropylcellulose. [7] (B) A tablet according to any one of items [1] to [6], wherein the excipient content is 5 to 99% by mass, preferably 5 to 90% by mass. [8] (D) A tablet according to any one of items [1] to [7], wherein the fluidizing agent contains silicon dioxide. [9] (D) A tablet according to any one of items [4] to [8], wherein the content of the fluidizing agent is 0.1 to 5% by mass, preferably 0.1 to 3% by mass.

[10] Furthermore, a tablet containing (E) vitamin as described in any one of items [1] to [9].

[11] (E) A tablet as described in [9], wherein the vitamin contains either vitamin B1 or vitamin B6.

[12] The tablet according to

[10] or

[11] , wherein the content of (E) vitamin is 0.1 to 10% by mass, preferably 0.1 to 3% by mass.

[13] A tablet according to any one of items

[10] to

[12] , wherein the mass per tablet is 150 to 500 mg, preferably 200 to 500 mg.

[14] A tablet according to any one of items [1] to

[13] , wherein the hardness of the tablet is 6.7 to 21 kgf, preferably 8.9 to 21 kgf.

[15] A tablet described in any one of items [1] to

[14] , having a disintegration time of 60 minutes or less.

[16] A tablet described in any one of the items [1] to

[15] of the 17th edition of the Japanese Pharmacopoeia, having a disintegration time of 60 minutes or less in the general test method / disintegration test method. [Examples]

[0079] The present invention will be described in more detail below with reference to examples. However, the scope of the present invention is not limited to these examples.

[0080] [Isoflavones] For the daidzein used, we used commercially available daidzein powder (derived from soybeans). For the genistein used, we used commercially available genistein powder (derived from soybeans). For the glycitein used, we used commercially available glycitein powder (derived from soybeans).

[0081] Other ingredients listed in Tables 1 to 4 were commercially available products. For cellulose, crystalline cellulose was used. For silicon dioxide, fine-grained silicon dioxide was used. For vitamin B1, thiamine hydrochloride was used. For vitamin B6, pyridoxine hydrochloride was used. For dextrin, a DE of 9.0 was used.

[0082] (Test 1: Evaluation of hardness and release from the pestle) (Comparative Example 1, Examples 1-9)

[0083] [Making tablets] Mixed powders were obtained using the formulations of the comparative examples and examples listed in Table 1. The obtained mixed powders were compressed using a single-shot tablet press to produce tablets (swallowing tablets) with a tablet diameter of 8 mm and a dose of 250 mg per tablet. The compression pressure was 5 kN.

[0084] <Measuring hardness> The hardness of the tablets obtained in the comparative examples and examples was measured using a hardness tester (Okada Seikou Co., Ltd. Portable Checker PC-30), and the average value of three tablets randomly sampled for each example is shown. The results are shown in Tables 1 and 2.

[0085] <Evaluation of release from pestle (tablet compressibility)> The tablets obtained in the comparative examples and examples were evaluated for release from the pestle according to the following criteria. The results are shown in Tables 1 and 2.

[0086] (Evaluation criteria for pestle release) ○: After compression, the compressed tablets separate from the punch tip, and there is no slight clouding of the punch. △: After compression, the compressed tablets separate from the punch tip, but there is slight clouding on the punch. ×: After compression, the compressed tablets stick to the punch tip and do not detach.

[0087] [Table 1]

[0088] As shown in Table 1, each example exhibited good hardness, indicating that the hardness increased with the addition of excipients. The addition of (C) lubricant, (D) fluidizer, and (E) vitamin further increased the hardness, demonstrating that the effect of hardness improvement increased with the addition of more components. Furthermore, each example also exhibited good tablet properties.

[0089] (Evaluation of collapse time and release from the pestle) (Examples 10-14) A mixed powder was obtained using the formulations described in Table 2. The obtained mixed powder was used to manufacture tablets (swallowing tablets) with a tablet diameter of 8 mm and a dose of 250 mg per tablet using a single-shot tablet press. The compression pressure was 5 kN.

[0090] <Measurement of decay time> The disintegration time was measured for n=6 using a disintegration tester (Toyama Sangyo Co., Ltd., model number: NT-40H) according to the method described in item "6.09" "Disintegration Test Method" of the 17th edition of the Japanese Pharmacopoeia. Water was used as the solution. The results are shown in Table 2.

[0091] <Evaluation of pestle release> The same evaluation criteria as above were used for evaluation. The results are shown in Table 2.

[0092] [Table 2]

[0093] As shown in Table 2, the isoflavone composition was preferable in terms of tablet disintegration when the mass ratio of daidzein to genistein was genistein:daidzein = 1:0.5 to 4.5. It was also found that the disintegration improved with the addition of vitamin (E).

[0094] The following tablets (Examples 15-17) were manufactured in the same manner as in Example 1. All of the tablets exhibited excellent hardness, release from the punch, and disintegration properties.

[0095] [Table 3]

[0096] The following tablets (Examples 18-21) were manufactured in the same manner as in Example 1. All of the tablets exhibited excellent hardness, release from the punch, and disintegration properties.

[0097] [Table 4]

[0098] The following tablets (Examples 22-31) were manufactured in the same manner as in Example 1. All tablets exhibited excellent hardness, release from the punch, and disintegration properties. In particular, tablets with a mass ratio of daidzein to genistein of 1:0.7-2.5 were superior.

[0099] [Table 5]

[0100] The following tablets (Examples 32-39) were manufactured in the same manner as in Example 1. All tablets exhibited excellent hardness, release from the punch, and disintegration properties. In particular, a glycitein / (daidzein + genistein) mass ratio of 0.05-0.2 was excellent.

[0101] [Table 6] [Industrial applicability]

[0102] The tablets of the present invention contain isoflavones with excellent health benefits, possess both hardness and compressibility, and are highly applicable to industrial use.

Claims

1. A tablet containing (A) isoflavones, (B) excipients, and (C) lubricants.

2. (A) The tablet according to claim 1, wherein the isoflavone comprises daidzein and genistein.

3. The tablet according to claim 2, wherein the mass ratio of daidzein to genistein is genistein:daidzein = 1:0.5 to 4.

5.

4. Furthermore, the tablet according to any one of claims 1 to 3, further comprising (D) a fluidizing agent.

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