Khellactone ester compound-containing solid composition and production method thereof, quality improvement method of khellactone ester compound-containing solid composition and oral composition

Abstract

To provide a khellactone ester compound-containing solid composition excellent in leachability of a khellactone ester compound in the khellactone ester compound-containing solid composition and a production method thereof, a quality improvement method of a khellactone ester compound-containing solid composition and an oral composition.SOLUTION: A khellactone ester compound-containing solid composition includes a khellactone ester compound and an excipient. If a content of the khellactone ester compound in the khellactone ester compound-containing solid composition calculated from a sample solution prepared in a treatment 1 is 100 mass%, a content of the khellactone ester compound in the khellactone ester compound-containing solid composition calculated from a sample solution prepared in a treatment 2 is 85 mass% or more.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a solid composition containing a kellactone ester compound and a method for producing the same, a method for improving the quality of a solid composition containing a kellactone ester compound, and an oral composition. [Background technology]

[0002] Kerlactone ester compounds are components contained in plant extracts, etc. Known examples of such plants include the longevity plant Peucedanum japonicum (also known as Peucedanum japonicum Thunb.), which belongs to the Apiaceae family and the genus Peucedanum.

[0003] Chomeisou is a food ingredient that has long been used in cooking and as a folk medicine in Okinawa Prefecture and other areas, and its extracts have been reported to have various effects, such as bone strengthening effects (see, for example, Patent Document 1), gout alleviation effects, liver function improvement effects, immunostimulating effects, anti-aging effects, anti-inflammatory effects, hair growth effects, antioxidant effects (see, for example, Patent Document 2), and anti-dental caries effects (see, for example, Patent Document 3). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2023-073564 [Patent Document 2] Japanese Patent Application Publication No. 2023-008538 [Patent Document 3] Japanese Patent Application Laid-Open No. 2003-119117 Summary of the Invention [Problem to be solved by the invention]

[0005] As described above, plant extracts containing kerulactone ester compounds are very useful materials and are incorporated into foods, beverages, etc. Furthermore, in order to enhance the functionality of the incorporated kerulactone ester compounds, it is important to improve their elution. On the other hand, in functional food products, it is necessary to guarantee the content of functional ingredients and to properly control the quality, and therefore, when quantifying the content of the incorporated functional ingredients, it is also necessary for the incorporated functional ingredients to be sufficiently eluted. Therefore, there is a demand for a technology to improve the elution of the compounded keralactone ester compounds, but at present no such technology has been provided.

[0006] The present invention aims to solve the above-mentioned conventional problems and achieve the following objects: That is, the present invention aims to provide a solid composition containing a kellactone ester compound that is excellent in the elution property of the kellactone ester compound, a method for producing the same, a method for improving the quality of a solid composition containing a kellactone ester compound, and an oral composition. [Means for solving the problem]

[0007] As a result of intensive research conducted by the present inventors to solve the above problems, they discovered that in the production of a solid composition containing a kellactone ester compound, by heating a liquid composition containing a kellactone ester compound and an excipient at a temperature of 85°C or higher and then drying it, the elution property of the kellactone ester compound can be increased, and furthermore, the solubility of the solid composition containing a kellactone ester compound in water can also be increased.

[0008] The present invention is based on the above findings of the present inventors, and the means for solving the above problems are as follows: <1> A solid composition containing a kellactone ester compound, which contains a kellactone ester compound and an excipient, The solid composition containing a kellactone ester compound is characterized in that the content of the kellactone ester compound in the solid composition containing a kellactone ester compound, calculated from the sample solution prepared in the following process 2, is 85 mass% or more, when the content of the kellactone ester compound in the solid composition containing a kellactone ester compound, calculated from the sample solution prepared in the following process 1, is taken as 100 mass%. <Process 1> Weigh out 250 to 750 mg of the solid composition containing the kellactone ester compound, add 8 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 12 mL of methanol, and stir at 40°C for 5 minutes to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is mixed with 4 mL of water and adjusted to a final volume of 50 mL with 50% by volume methanol to prepare a sample solution. <Process 2> Weigh out 250 to 750 mg of the solid composition containing the kellactone ester compound, add 10 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 10 mL of methanol, and stir at room temperature to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is adjusted to a constant volume of 50 mL with 50% by volume methanol to prepare a sample solution. <2> The above-mentioned compound is at least one selected from the group consisting of hyuganin D, cis-3'-acetyl-4'-tigloyl quellactone, poisedanocoumarin III, isosamidin, trans-3'-acetyl-4'-senecioyl quellactone, and pteryxin. <1> 1. A solid composition containing the keralactone ester compound described in 1. <3> The above-mentioned keralactone ester compound is contained in a plant extract. <1> or <2> 1. A solid composition containing the keralactone ester compound described in 1. <4> The plant is Chou-mei-sou. <3> 1. A solid composition containing the keralactone ester compound described in 1. <5> A method for producing a solid composition containing a kellactone ester compound, the solid composition containing a kellactone ester compound and an excipient, comprising: preparing a liquid composition containing the kerulactone ester compound and the excipient; heating the liquid composition to a temperature of 85°C or greater; and drying the liquid composition after the heating. <6> The above-mentioned compound is at least one selected from the group consisting of hyuganin D, cis-3'-acetyl-4'-tigloyl quellactone, poisedanocoumarin III, isosamidin, trans-3'-acetyl-4'-senecioyl quellactone, and pteryxin. <5> 1. A method for producing a solid composition containing a kerulactone ester compound according to claim 1. <7> The above-mentioned keralactone ester compound is contained in a plant extract. <5> or <6> 1. A method for producing a solid composition containing a kerulactone ester compound according to claim 1. <8> The plant is Chou-mei-sou. <7> 1. A method for producing a solid composition containing a kerulactone ester compound according to claim 1. <9> The content of the kellactone ester compound in the solid composition containing the kellactone ester compound, calculated from the sample solution prepared in the following process 2, is 85% by mass or more when the content of the kellactone ester compound in the solid composition containing the kellactone ester compound, calculated from the sample solution prepared in the following process 1, is taken as 100% by mass. <5> from <8> 1. A method for producing a solid composition containing a kellactone ester compound according to any one of the above. <Process 1> Weigh out 250 to 750 mg of the solid composition containing the kellactone ester compound, add 8 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 12 mL of methanol, and stir at 40°C for 5 minutes to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is mixed with 4 mL of water and adjusted to a final volume of 50 mL with 50% by volume methanol to prepare a sample solution. <Process 2> Weigh out 250 to 750 mg of the solid composition containing the kellactone ester compound, add 10 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 10 mL of methanol, and stir at room temperature to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is adjusted to a constant volume of 50 mL with 50% by volume methanol to prepare a sample solution. <10> A method for improving the quality of a solid composition containing a kellactone ester compound, the solid composition containing a kellactone ester compound and an excipient, comprising: preparing a liquid composition containing the kerulactone ester compound and the excipient; heating the liquid composition to a temperature of 85°C or greater; and drying the liquid composition after the heating. The method for improving the quality of a solid composition containing a kellactone ester compound is characterized in that the improvement in the quality of the solid composition containing a kellactone ester compound includes improving the elution property of the kellactone ester compound. <11> The above-mentioned compound is at least one selected from the group consisting of hyuganin D, cis-3'-acetyl-4'-tigloyl quellactone, poisedanocoumarin III, isosamidin, trans-3'-acetyl-4'-senecioyl quellactone, and pteryxin. <10> 2. A method for improving the quality of a solid composition containing a kerulactone ester compound according to claim 1. <12> The above-mentioned keralactone ester compound is contained in a plant extract. <10> or <11> 2. A method for improving the quality of a solid composition containing a kerulactone ester compound according to claim 1. <13> The plant is Chou-mei-sou. <12> 2. A method for improving the quality of a solid composition containing a kerulactone ester compound according to claim 1. <14> The improvement in quality of the solid composition containing a kellactone ester compound includes improving the solubility of the solid composition containing a kellactone ester compound in water. <10> from <13> 1. A method for improving the quality of a solid composition containing a kellactone ester compound according to any one of the above. <15> The content of the kellactone ester compound in the solid composition containing the kellactone ester compound, calculated from the sample solution prepared in the following process 2, is 85% by mass or more when the content of the kellactone ester compound in the solid composition containing the kellactone ester compound, calculated from the sample solution prepared in the following process 1, is taken as 100% by mass. <10> from <14> 1. A method for improving the quality of a solid composition containing a kellactone ester compound according to any one of the above. <Process 1> Weigh out 250 to 750 mg of the solid composition containing the kellactone ester compound, add 8 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 12 mL of methanol, and stir at 40°C for 5 minutes to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is mixed with 4 mL of water and adjusted to a final volume of 50 mL with 50% by volume methanol to prepare a sample solution. <Process 2> Weigh out 250 to 750 mg of the solid composition containing the kellactone ester compound, add 10 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 10 mL of methanol, and stir at room temperature to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is adjusted to a constant volume of 50 mL with 50% by volume methanol to prepare a sample solution. <16> The aforementioned <1> from <4> 1. A composition for oral administration, characterized by containing the solid composition containing a kellactone ester compound according to any one of the above. [Effects of the Invention]

[0009] According to the present invention, the above-mentioned problems of the prior art can be solved and the above-mentioned object can be achieved, and it is possible to provide a solid composition containing a kellactone ester compound that has excellent elution properties of the kellactone ester compound in the solid composition containing a kellactone ester compound, a method for producing the same, a method for improving the quality of a solid composition containing a kellactone ester compound, and an oral composition. DETAILED DESCRIPTION OF THE INVENTION

[0010] (Solid composition containing kellactone ester compound and method for producing the solid composition containing kellactone ester compound) The solid composition containing a kellactone ester compound of the present invention contains at least a kellactone ester compound and an excipient, and may further contain other components as required. The method for producing the solid composition containing a kellactone ester compound of the present invention is not particularly limited and can be selected appropriately depending on the purpose, but the solid composition can be preferably produced by the method for producing the solid composition containing a kellactone ester compound of the present invention. The method for producing the solid composition containing a kellactone ester compound of the present invention will be explained below, along with the solid composition containing a kellactone ester compound of the present invention.

[0011] [Method of producing a solid composition containing a kellactone ester compound] The method for producing a solid composition containing a kellactone ester compound of the present invention is a method for producing a solid composition containing a kellactone ester compound, which contains a kellactone ester compound and an excipient, and includes at least a liquid composition preparation step, a heating step, and a drying step, and may further include other steps as necessary. According to the method for producing a solid composition containing a kellactone ester compound of the present invention, the solid composition containing a kellactone ester compound of the present invention can be suitably produced, but the solid composition containing a kellactone ester compound produced by the method for producing a solid composition containing a kellactone ester compound of the present invention is not limited to the solid composition containing a kellactone ester compound of the present invention.

[0012] <Liquid composition preparation process> The liquid composition preparation step is a step of preparing a liquid composition containing a kerulactone ester compound and an excipient.

[0013] <<Liquid composition>> The liquid composition (hereinafter sometimes referred to as "prepared liquid") contains at least a kerulactone ester compound and an excipient, and may further contain other components as required.

[0014] -solvent- The solvent for the liquid composition is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent of water and a hydrophilic solvent.

[0015] The water is not particularly limited and can be appropriately selected depending on the purpose. Examples include pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, and water obtained by various treatments. Examples of treatments for water include purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, etc. Water that can be used as the extraction solvent also includes purified water, hot water, ion-exchanged water, saline, phosphate buffer, phosphate-buffered saline, etc. The water may be used alone or in combination of two or more types.

[0016] The hydrophilic solvent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include lower alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones, such as acetone and methyl ethyl ketone; and polyhydric alcohols having 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin. These may be used alone or in combination of two or more.

[0017] The amount of the hydrophilic solvent used relative to the amount of water in the mixed solvent is not particularly limited and can be appropriately selected depending on the purpose.

[0018] -Kerlactone ester compounds- The kerulactone ester compound is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include hyuganin D, cis-3'-acetyl-4'-tigloylkhellactone, peucedanocoumarin III, isosamidin, trans-3'-acetyl-4'-senecioylkhellactone, pteryxin, etc. These may be used alone or in combination of two or more.

[0019] The above-mentioned Hyuganin D is a compound represented by the following structural formula. [ka]

[0020] The cis-3'-acetyl-4'-tigloyl kerulactone is a compound represented by the following structural formula. [ka]

[0021] The poisedanocoumarin III is a compound represented by the following structural formula: [ka]

[0022] The isosamidin is a compound represented by the following structural formula: [ka]

[0023] The trans-3'-acetyl-4'-senecioyl kerulactone is a compound represented by the following structural formula. [ka]

[0024] The pteryxin is a compound represented by the following structural formula: [ka]

[0025] The kerulactone ester compounds may be synthetic products or may be those contained in plant extracts, but those contained in plant extracts are preferred.

[0026] The plant is not particularly limited as long as it contains the kerulactone ester compound and can be appropriately selected depending on the purpose, and examples thereof include plants belonging to the Apiaceae, Rubiaceae, and Sarcocarpaceae families. Among these, plants belonging to the Apiaceae family, the genus Peucedanum, are preferred, and Chou-mei-sou (also known as Peucedanum japonicum, Thunb.) is more preferred. The chomeisou is a perennial plant that grows on the coast and is distributed in areas west of Kanto, Shikoku, Kyushu, Okinawa, Korea, mainland China, the Philippines, etc., and is easily available in these areas.

[0027] The plant extract containing the kerulactone ester compounds may be prepared from the part of the plant used as the raw material for extraction, or may be a commercially available product.

[0028] For example, in the case of Chomeisou, the raw material for extraction (extraction part) is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include fruit, leaves, stems, flowers, underground parts, etc. The underground parts include roots and rhizomes. The extraction site may be one site only, or two or more sites. The shape, structure, and size of the extraction raw material are not particularly limited and can be appropriately selected depending on the purpose.

[0029] The method for preparing the raw material for extraction is not particularly limited and can be selected appropriately depending on the purpose. For example, the extracted part can be dried and then crushed directly or using a crusher. The dried material can be subjected to solvent extraction either directly or after crushing. The drying can be performed in the sun or using a commonly used dryer.

[0030] The plant extract containing the kellactone ester compound can be easily obtained by a method generally used for plant extraction. The form of the plant extract is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include the extract itself, a diluted extract, a concentrated extract, a dried product thereof, a roughly purified product thereof, and a purified product thereof.

[0031] The extraction method is not particularly limited and can be selected appropriately depending on the purpose, and examples include a method of extracting using any extraction device at room temperature or under reflux heating, and more specifically, a method of adding the extraction material to a treatment tank filled with an extraction solvent, leaving it to stand for, for example, 30 minutes to 4 hours while stirring as necessary to elute the soluble components, and then filtering to remove the extraction residue to obtain an extract. The extract may be further dried after distilling off the extraction solvent. Alternatively, the extract may be used as a raw material for extraction after pre-treatment such as degreasing with a non-polar solvent such as hexane. Pre-treatment such as degreasing allows for efficient extraction with a polar solvent.

[0032] The extraction conditions (extraction time and extraction temperature), extraction solvent, and amount of extraction solvent used are not particularly limited and can be appropriately selected depending on the purpose.

[0033] The extraction solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent of water and a hydrophilic solvent. Examples of the water, hydrophilic solvent, or mixed solvent of water and a hydrophilic solvent include the same solvents as those of the liquid composition described above.

[0034] The amount of the hydrophilic solvent used relative to the water in the mixed solvent is not particularly limited and can be appropriately selected depending on the purpose. However, when a lower alcohol is used, it is preferable to add 1 to 90 parts by volume relative to 10 parts by volume of water, when a lower aliphatic ketone is used, it is preferable to add 1 to 40 parts by volume relative to 10 parts by volume of water, and when a polyhydric alcohol is used, it is preferable to add 1 to 90 parts by volume relative to 10 parts by volume of water.

[0035] The temperature of the extraction solvent is not particularly limited and can be appropriately selected depending on the purpose, but it is preferably used at a temperature between room temperature and the boiling point of the solvent.

[0036] The obtained plant extract may be subjected to treatments such as dilution, concentration, drying, purification, etc. according to conventional methods to obtain a diluted product, concentrate, dried product, roughly purified product, purified product, etc. of the plant extract.

[0037] The method for purifying the plant extract is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, etc. Purification by the above purification methods can increase the concentration of active ingredients and remove unnecessary substances.

[0038] The total content of the kellactone ester compounds in the plant extract is not particularly limited and can be appropriately selected depending on the purpose.

[0039] The content of the kellactone ester compound in the liquid composition can be appropriately selected depending on the content in the kellactone ester compound-containing solid composition. The content of the kellactone ester compounds in the kellactone ester compound-containing solid composition is not particularly limited and can be selected appropriately depending on the purpose, but the total content of the kellactone ester compounds is preferably 0.0001% by mass to 70% by mass, more preferably 0.001% by mass to 30% by mass, and particularly preferably 0.01% by mass to 15% by mass.

[0040] -Excipients- The excipient is not particularly limited as long as it can be used in foods, beverages, and pharmaceuticals, and can be appropriately selected depending on the purpose, and examples thereof include dextrin, etc. These may be used alone or in combination of two or more.

[0041] The dextrin is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include dextrins with a linear structure, dextrins with a branched structure, a mixture of dextrins with a linear structure and dextrins with a branched structure, dextrins with a cyclic structure (e.g., α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, Cluster Dextrin (registered trademark)), etc. These may be used alone or in combination of two or more.

[0042] The excipients used may be those produced by known methods or commercially available products.

[0043] The content of the excipient in the liquid composition can be appropriately selected depending on the content in the solid composition containing the kellactone ester compound. The content of the excipient in the solid composition containing the keratinocyte ester compound is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 40% by mass or more, more preferably 50% by mass or more, even more preferably 70% by mass or more, and particularly preferably 80% by mass or more. The upper limit of the content of the excipient in the solid composition containing the kerulactone ester compound is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include 99% by mass or less.

[0044] -Other ingredients- The other components in the liquid composition are not particularly limited as long as they do not impair the effects of the present invention and can be appropriately selected depending on the purpose, and examples include components other than the kellactone ester compounds contained in the above-mentioned plant extracts, auxiliary raw materials or additives used in the production of ordinary oral compositions, etc. The other components may be used alone or in combination of two or more.

[0045] The auxiliary raw materials or additives used in the production of the above-mentioned conventional oral compositions are not particularly limited and can be selected appropriately depending on the purpose, and examples include various additives such as pH adjusters, glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, corn syrup, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorants, flavorings, preservatives, solvents, stabilizers, and antioxidants.

[0046] The content of other components in the liquid composition or the solid composition containing a kellactone ester compound is not particularly limited in the present invention and can be appropriately selected depending on the purpose.

[0047] The method for producing the liquid composition is not particularly limited and can be appropriately selected depending on the purpose. For example, a method in which the excipient is added to a liquid containing the kellactone ester compound and the mixture is stirred can be mentioned. The stirring conditions are not particularly limited and can be appropriately selected depending on the purpose. During the stirring, the mixture may be heated as needed to dissolve the excipient. The heating temperature is not particularly limited and can be appropriately selected depending on the purpose.

[0048] <Heating process> The heating step is a step of heating the liquid composition to a temperature of 85°C or higher.

[0049] The temperature to which the liquid composition is heated is not particularly limited as long as it is 85° C. or higher, and can be appropriately selected depending on the purpose.

[0050] The time for which the liquid composition is heated is not particularly limited and can be appropriately selected depending on the purpose.

[0051] The combination of temperature and time for heating the liquid composition is not particularly limited and can be appropriately selected depending on the purpose, and examples include heating at 125 to 135°C for 10 to 30 seconds, heating at 85 to 95°C for 10 to 60 minutes, heating at 121°C for 0.5 to 5 minutes (autoclave treatment), etc. Among these, heating at 125 to 135°C for 10 to 30 seconds is preferred.

[0052] The heating method is not particularly limited, and any known heating device can be appropriately selected.

[0053] <Drying process> The drying step is a step of drying the liquid composition after heating to form a solid composition.

[0054] The drying method is not particularly limited and may be appropriately selected from known methods, such as freeze drying, spray drying, hot air drying, etc. Among these, spray drying is preferred.

[0055] The drying conditions are not particularly limited and can be appropriately selected depending on the purpose.

[0056] The dried product obtained by the drying process can be pulverized into powder by a known pulverization method, for example, using a mortar, an impact pulverizer, etc. If necessary, the powder can be sieved to obtain a powder with a uniform particle size.

[0057] The form of the solid composition is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include powder, etc. The powder can also be used to form granules or tablets.

[0058] <Other processes> The other steps are not particularly limited as long as they do not impair the effects of the present invention, and can be selected appropriately depending on the purpose. For example, they may include a step of preparing a plant extract containing the above-mentioned kerulactone ester compounds.

[0059] [Solid composition containing kellactone ester compound] The solid composition containing the kellactone ester compound (hereinafter, sometimes referred to as "solid preparation") is excellent in the dissolution property of the kellactone ester compound.

[0060] The content of the kellactone ester compound in the solid composition containing the kellactone ester compound, calculated from the sample solution prepared in the following treatment 2 (hereinafter sometimes referred to as "treatment 2 / treatment 1"), is 85 mass% or more when the content of the kellactone ester compound in the solid composition containing the kellactone ester compound, calculated from the sample solution prepared in the following treatment 1, is taken as 100 mass%.

[0061] <Process 1> Weigh out 250 to 750 mg of the solid composition containing the kellactone ester compound, add 8 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 12 mL of methanol, and stir at 40°C for 5 minutes to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is mixed with 4 mL of water and adjusted to a final volume of 50 mL with 50% by volume methanol to prepare a sample solution.

[0062] According to the method of treatment 1, the kellactone ester compound is easily eluted regardless of the type of the solid composition containing the kellactone ester compound.

[0063] <Process 2> Weigh out 250 to 750 mg of the solid composition containing the kellactone ester compound, add 10 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 10 mL of methanol, and stir at room temperature to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is adjusted to a constant volume of 50 mL with 50% by volume methanol to prepare a sample solution. The room temperature refers to a temperature of 20°C to 25°C. The amount of the solid composition containing the kellactone ester compound weighed in the second treatment is the same as that in the first treatment.

[0064] According to the method of treatment 2, the elution property of the kellactone ester compound varies depending on the type of the solid composition containing the kellactone ester compound.

[0065] The amount of the solid composition containing the kellactone ester compound weighed in the treatment 1 and the treatment 2 is within a range of 250 to 750 mg. By keeping it within this range, there are no problems with the pretreatment operation such as dispersibility, and the evaluation can be performed under conditions with excellent quantitative accuracy. The amount of the kellactone ester compound contained in the kellactone ester compound-containing solid composition is not particularly limited and can be appropriately selected depending on the purpose. For example, the amount of each kellactone ester compound may be in the range of 2.6 μmol to 509 μmol.

[0066] There are no particular limitations on the method for calculating the content of the kellactone ester compound in the kellactone ester compound-containing solid composition from the sample solutions prepared by the process 1 and the process 2, and it can be appropriately selected depending on the purpose. For example, as described in the section [Examples] below, the content of the kellactone ester compound in the sample solution is measured by high performance liquid chromatography, and the content of the kellactone ester compound in the kellactone ester compound-containing solid composition is calculated from the measurement results.

[0067] The ratio of treatment 2 / treatment 1 is not particularly limited as long as it is 85% by mass or more and can be appropriately selected depending on the purpose, but it is preferably 90% by mass or more, and more preferably 95% by mass or more.

[0068] As shown in the Examples section below, the solid composition containing the kellactone ester compound has excellent solubility in water, and therefore can be easily incorporated into oral compositions such as foods and beverages. The degree of solubility in water of the solid composition containing the kellactone ester compound is not particularly limited and can be appropriately selected depending on the purpose.

[0069] There are no particular restrictions on the dosage, administration site, administration period, and administration interval (hereinafter referred to as "usage amount, administration site, administration period, and administration interval") of the solid composition containing the keralactone ester compound, and these can be selected appropriately depending on the purpose.

[0070] The amount of the solid composition containing the kellactone ester compound to be used (hereinafter sometimes referred to as "intake amount") is not particularly limited and can be selected appropriately depending on the purpose. For example, it can be 0.01 mg to 20 mg per day, calculated as the total amount of the kellactone ester compound.

[0071] The solid composition containing the kerulactone ester compound is highly safe and can be used on a daily basis, and therefore can be used continuously, for example, once or more times a day.

[0072] The solid composition containing the kellactone ester compound can exhibit the various excellent effects of the kellactone ester compound, and can be used in all applications where it is meaningful to exhibit the various excellent effects of the kellactone ester compound.

[0073] The solid composition containing the kellactone ester compound can be widely used in a variety of fields, including food and beverages, pharmaceuticals, etc. It can also be suitably used in oral compositions, which will be described later.

[0074] The solid composition containing the keralactone ester compound is suitable for use in humans, but can also be used in animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as its functional effects are maintained.

[0075] (Method for improving the quality of a solid composition containing a keralactone ester compound) The method for improving the quality of a solid composition containing a kellactone ester compound of the present invention (hereinafter sometimes referred to as the "quality improvement method") is a method for improving the quality of a solid composition containing a kellactone ester compound, which contains a kellactone ester compound and an excipient, and includes at least a liquid composition preparation step, a heating step, and a drying step, and may further include other steps as necessary.

[0076] The improvement in quality of the solid composition containing a kellactone ester compound includes at least an improvement in the elution property of the kellactone ester compound, and preferably further includes an improvement in the solubility of the solid composition containing a kellactone ester compound in water.

[0077] In this specification, improving the elution property of the kellactone ester compound means increasing the elution property of the kellactone ester compound. Furthermore, improving the solubility of the solid composition containing a kellactone ester compound in water means increasing the solubility of the solid composition containing a kellactone ester compound in water.

[0078] <Liquid composition preparation process> The liquid composition preparation step is a step of preparing a liquid composition containing the kellactone ester compound and the excipient, and is the same as the liquid composition preparation step in the above-mentioned method for producing a solid composition containing a kellactone ester compound, and the preferred aspects are also the same.

[0079] <Heating process> The heating step is a step of heating the liquid composition at a temperature of 85° C. or higher, and is the same as the heating step in the above-mentioned method for producing a solid composition containing a kellactone ester compound, and the preferred embodiments are also the same.

[0080] <Drying process> The drying step is a step of drying the liquid composition after the heating, and is the same as the drying step in the method for producing a solid composition containing a kellactone ester compound described above, and the preferred embodiments are also the same.

[0081] <Other processes> The other steps in the quality improvement method are not particularly limited as long as they do not impair the effects of the present invention, and can be selected appropriately depending on the purpose. For example, they may be the same as the other steps in the above-mentioned method for producing a solid composition containing a kerulactone ester compound.

[0082] (Oral composition) The oral composition of the present invention contains the solid composition containing the kellactone ester compound of the present invention, and may further contain other ingredients as required.

[0083] The oral composition of the present invention contains the above-mentioned solid composition containing a kellactone ester compound, and therefore, due to the action of the kellactone ester compound contained in the solid composition containing a kellactone ester compound, it can be used for various purposes such as bone strengthening, gout relief, liver function improvement, immune activation, anti-aging, anti-inflammation, hair growth, and antioxidant properties.

[0084] The oral composition refers to a composition that is unlikely to be harmful to human health and is taken orally or by administration through the gastrointestinal tract in normal social life, and is not limited to administrative classifications such as food, medicine, quasi-drug, etc. Therefore, the oral composition broadly includes orally taken general foods, health foods (functional food and drink), health functional foods (foods for specified health uses, foods with nutrient functions, foods with functional claims), quasi-drugs, medicines, etc.

[0085] The type of the oral composition is not particularly limited and can be appropriately selected depending on the purpose. Examples of the oral composition include beverages such as tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, alcoholic drinks, coffee drinks, and coffee-containing soft drinks (including concentrated liquids and powders for adjusting these beverages); frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba noodles, udon noodles, vermicelli noodles, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; confectioneries such as candy, candy, gum, chocolate, candy tablets, snacks, biscuits, jelly, jam, cream, baked goods, and bread; seafood such as crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oysters, saury, squid, ark shells, scallops, abalone, sea urchin, salmon roe, and tokobushi sea bass; and fish products such as kamaboko (fish paste), hamachi (fish paste), and the like. processed seafood and livestock foods such as cheese, sausages, etc.; dairy products such as processed milk and fermented milk; oils and fats and oil-processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressings, etc.; condiments such as sauces and dressings; retort pouch foods such as curry, stew, oyakodon, rice porridge, rice porridge, Chinese rice bowl, katsudon, tempura bowl, unadon, hayashi rice, oden, mabo dolph, beef bowl, meat sauce, egg soup, omelet rice, gyoza, shumai, hamburger steak, meatballs, etc.; side dishes such as salads and pickles; health, beauty, and nutritional supplements in various forms; pharmaceuticals and quasi-drugs such as tablets, powders, granules, capsules, extracts, syrups, drinks, lozenges, mouthwash, etc.; oral fresheners used in the mouth such as mouth fresheners and anti-halitants, and toothpaste.

[0086] <Solid composition containing kellactone ester compound> The solid composition containing a kellactone ester compound is the above-mentioned solid composition containing a kellactone ester compound of the present invention.

[0087] The content of the solid composition containing the kellactone ester compound in the oral composition is not particularly limited and can be adjusted appropriately depending on the form of the oral composition and the amount of the kellactone ester compound, etc., but is preferably 0.0001% by mass to 20% by mass, and more preferably 0.0001% by mass to 10% by mass, calculated as the total amount of the kellactone ester compound.

[0088] <Other ingredients> The other components in the oral composition are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include the same components as those in the liquid composition described above. The other components may be used alone or in combination of two or more.

[0089] The content of the other components in the oral composition is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

[0090] The method for producing the oral composition is not particularly limited and can be appropriately selected depending on the form of the oral composition.

[0091] The amount of the oral composition to be used, the period of use, the interval between uses, etc. are not particularly limited and can be appropriately selected depending on the purpose.

[0092] The oral compositions are suitable for use in humans, but can also be used in animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as the respective effects are achieved. [Example]

[0093] Test examples and formulation examples of the present invention will be explained below, but the present invention is not limited to these test examples and formulation examples.

[0094] (Test Example 1) [Preparation of prepared solution] 1,000 mL of 50% ethanol (volume) was added to 100 g of the roots of Choumeisou, and extraction was carried out at 90°C using a reflux condenser for 1 hour, after which the mixture was filtered through a 200-mesh sieve to obtain Extract No. 1. 1,000 mL of 50% ethanol (volume) was added to the extraction residue, and the mixture was similarly reflux-extracted, after which it was filtered through a 200-mesh sieve to obtain Extract No. 2. The obtained No. 1 extract and No. 2 extract were filtered through diatomaceous earth and concentrated (solvent removal) to obtain concentrated solutions. An excipient (Cluster Dextrin (registered trademark), Glico Nutrition Foods Co., Ltd.) was added to the concentrated solution, and the mixture was heated (60±5°C) and stirred until the excipient was dissolved, to obtain a prepared solution.

[0095] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 80% by mass.

[0096] <Untreated product> The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0097] <Instant heating product> The prepared solution was heated for 20 seconds at 130±3° C. The heated prepared solution was freeze-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as a “flash-heated product”).

[0098] <Heated product 75> The preparation was heated for 30 minutes at 75° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 75”).

[0099] <Heated product 85> The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0100] <Autoclave product> The preparation was autoclaved (121°C, 1 minute). The autoclaved preparation was freeze-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "autoclaved product").

[0101] [evaluation] <Dissolution> The dissolution properties of the following six types of kerulactone ester compounds contained in each of the preparations obtained above were examined as follows. (1) Hyuganin D (2) cis-3'-acetyl-4'-tigloyl querlactone (3) Poisedanocoumarin III (4) Isosamidin (5) trans-3'-acetyl-4'-senecioyl kerulactone (6) Pteryxin

[0102] Specifically, sample solutions for treatments 1 and 2 were prepared as follows, and the content of the kellactone ester compound in the solid formulation calculated from the sample solution prepared in treatment 2 was calculated as a percentage of the content of the kellactone ester compound in the solid formulation calculated from the sample solution prepared in treatment 1 (hereinafter sometimes referred to as "content of the kellactone ester compound"), which was taken as 100% by mass, to evaluate the dissolution properties of the formulation.

[0103] <<Preparation of sample solution>> -Process 1- 500 mg of the powder formulation obtained above was weighed and placed in a No. 8 (110 mL) screw cap. 8 mL of water was added, and the mixture was thoroughly suspended by ultrasonic irradiation while stirring with a spatula. 1 g of diatomaceous earth (Diatomaceous Earth Celite 545 (Fujifilm Wako Pure Chemical Industries)) was added, and the suspension was further suspended by ultrasonic irradiation. Next, 12 mL of methanol was added, and the mixture was heated and stirred (40°C, 5 minutes, stirring until uniformly suspended) to obtain a powder suspension. Separately, a No. 6 filter paper was soaked in 50% by volume methanol and placed in a Kiriyama funnel (φ40 mm) and prepared by suction. Next, approximately 10 mL of 50% by volume methanol was added to 1 g of diatomaceous earth (Diatomaceous Earth Celite 545 (Fujifilm Wako Pure Chemical Industries)), and the mixture was suspended by ultrasonic irradiation. The suspension was then filtered by suction using the Kiriyama funnel prepared earlier, and the filtrate was discarded. Using this Kiriyama funnel loaded with diatomaceous earth, the powder suspension prepared earlier was suction filtered while being gently shaken by hand to make it uniform, and the filtrate was collected in a new No. 8 screw cap. The container containing the powder suspension was washed with 8 mL of 50% by volume methanol, followed by suction filtration twice, and the filtrate was collected together with the previous filtrate. All of the filtrate was transferred to a 50 mL volumetric flask containing 4 mL of water, and the filtrate was diluted to 50 mL while the equipment containing the filtrate was washed with 50% by volume methanol to obtain a powder extract. The powder extract was filtered through a 0.2 μm membrane filter (PTFE membrane filter), and the initial flow was discarded. The filtrate was used as the sample solution.

[0104] -Process 2- 500 mg of the powder formulation obtained above was weighed and placed in a No. 8 (110 mL) screw cap. 10 mL of water was added and thoroughly suspended by ultrasonic irradiation while stirring with a spatula. 1 g of diatomaceous earth (Diatomaceous Earth Celite 545 (Fujifilm Wako Pure Chemical Industries)) was added and further suspended by ultrasonic irradiation. Next, 10 mL of methanol was added and the mixture was shaken and stirred at room temperature (20°C to 25°C) (to achieve a uniform suspension) to obtain a powder suspension. Separately, a No. 6 filter paper was soaked in 50% by volume methanol and placed in a Kiriyama funnel (φ40 mm) and prepared by suction. Next, approximately 10 mL of 50% by volume methanol was added to 1 g of diatomaceous earth (Diatomaceous Earth Celite 545 (Fujifilm Wako Pure Chemical Industries)), and the mixture was suspended by ultrasonic irradiation. The suspension was then filtered by suction using the Kiriyama funnel prepared earlier, and the filtrate was discarded. Using this Kiriyama funnel loaded with diatomaceous earth, the previously prepared powder suspension was suction filtered while being gently shaken by hand to make it uniform, and the filtrate was collected in a new No. 8 screw cap. The container containing the powder suspension was washed with 10 mL of 50% by volume methanol, followed by suction filtration twice, and the filtrate was collected together with the previous filtrate. All of the filtrate was transferred to a 50 mL measuring flask, and the equipment containing the filtrate was washed with 50% by volume methanol while the volume was increased to 50 mL to obtain a powder extract. The powder extract was filtered through a 0.2 μm membrane filter (PTFE membrane filter), and the initial flow was discarded. The filtrate was used as the sample solution.

[0105] <<Calculation of the content of kerulactone ester compounds in solid dosage forms>> Using the following standard solutions, the content of the kellactone ester compound in the sample solution was measured by high performance liquid chromatography, and the content of the kellactone ester compound in the solid preparation was calculated from the measurement results.

[0106] - Preparation of standard solutions - The standard solution was prepared as follows: 7-ethoxy-4-methylcoumarin (7-ethoxy-4-methylcoumarin) was precisely weighed in an amount equivalent to 2.6 μmol to 516 μmol, dissolved in methanol, and made up to 10 mL, creating solution (1). 2 mL of this solution (1) was collected using a volumetric pipette and made up to 20 mL with methanol, creating solution (2). 2 mL of this solution (2) was further collected using a volumetric pipette, mixed with 2 mL of purified water, and then made up to 25 mL with 50% by volume methanol, creating solution (3). This solution (3) was filtered through a 0.2 μm polytetrafluoroethylene (PTFE) membrane filter, and the initial flow was discarded. The filtrate was placed in a vial and used as the standard solution.

[0107] -High-performance liquid chromatography operating conditions- Column: SunShell C30 (2.6 μm, 3.0 × 100 mm, Chromanic Technologies) Mobile phase: (A) H2O:TFA:methanol:THF =400:0.2:50:55 (B) Acetonitrile Mobile phase conditions; 0-50 minutes Mobile phase (B) 0%, 50.1-55 minutes Mobile phase (B) 95%, 55.1-70 minutes Mobile phase (B) 0% Flow rate; 1.0mL / min Column temperature: 40℃ Injection volume: 15μL Detector: UV 320nm

[0108] -Quantitative- The quantification was carried out as follows. The amount of 7-ethoxy-4-methylcoumarin used to prepare the standard solution (W std ) and the molar concentration of the standard substance in the standard solution (C std ) is found.

number

[0109] From the results of high performance liquid chromatography analysis of the standard substance, the peak area value (a std ) is obtained. In addition, from the results of high performance liquid chromatography analysis of the sample solution, the peak area value (a 1~6 The molar concentration (C 1~6 ) was calculated, and the content of the kerulactone ester compound in the preparation (Ct 1~6 ) is found.

number

number

[0110] The relative molar sensitivity (RMS) and molecular weight (Mw) of the kerulactone ester compounds are as follows: (1) Hyuganin D RMS: 0.930, Mw: 374.38 (2) cis-3'-acetyl-4'-tigloyl querlactone RMS: 0.927, Mw: 386.40 (3) Poisedanocoumarin III RMS: 0.921, Mw: 386.40 (4) Isosamidin RMS: 0.915, Mw: 386.40 (5) trans-3'-acetyl-4'-senecioyl kerulactone RMS: 0.922, Mw: 386.40 (6) Pteryxin RMS: 0.912, Mw: 386.40

[0111] The content of kerulactone ester compounds in the solid preparation calculated from the sample solution obtained in Treatment 2 was calculated as a percentage of the content of kerulactone ester compounds in the solid preparation calculated from the sample solution obtained in Treatment 1, which was set to 100% by mass. The results are shown in Table 1.

[0112] [Table 1] In Table 1, (1) to (6) in the column of the content of kerulactone ester compounds represent the following compounds. (1): Hyuganin D (2) : cis-3'-acetyl-4'-tigloyl kerlactone (3) : Poisedanocoumarin III (4) : Isosamidin (5) : trans-3'-acetyl-4'-senecioyl keratinone (6): Pteryxin

[0113] As shown in Table 1, among the preparations that were heated before freeze-drying, the instantaneous heating product, the heated product 85, and the autoclave product showed increased elution of kerulactone ester compounds.

[0114] <Solubility> Each of the preparations obtained above was added to water to prepare an aqueous solution with a preparation concentration of 0.4% by mass. The transmittance of the aqueous solution at a wavelength of 600 nm was measured using an ultraviolet-visible spectrophotometer (model number: UV-1900i, manufactured by Shimadzu Corporation). The transmittance of each sample was calculated based on the transmittance of distilled water at a wavelength of 600 nm being 100%. The results are shown in Table 2.

[0115] [Table 2]

[0116] As shown in Table 2, the solubility of the solid formulation in water was increased by heat-treating the preparation before freeze-drying.

[0117] (Test Example 2) [Preparation of prepared solution] A preparation solution was produced in the same manner as in Test Example 1, except that the amount of excipient used was changed so that the content of the excipient in the preparation was 80% by mass or 70% by mass.

[0118] [Production of formulations] Each formulation was prepared as follows.

[0119] <Untreated product> The prepared solution was spray-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "untreated product"). The content of the excipient in the preparation was 80% by mass.

[0120] <Instant heating product> The preparation was heated at 130±3°C for 20 seconds. The heated preparation was spray-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "flash-heated product"). The content of excipients in the preparation was 80% by mass.

[0121] <Heated product 85-1> The preparation solution was heated at 85°C for 30 minutes. The heated preparation solution was spray-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "heated product 85-1"). The content of excipients in the preparation was 80% by mass.

[0122] <Heated product 85-2> The preparation solution was heated at 85°C for 30 minutes. The heated preparation solution was spray-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "heated product 85-2"). The content of excipients in the preparation was 70% by mass.

[0123] [evaluation] The dissolution and solubility of each preparation obtained in Test Example 2 were evaluated in the same manner as in Test Example 1. The results of dissolution are shown in Table 3, and the results of solubility are shown in Table 4. In Table 3, (1) to (6) in the column of kerulactone ester compound content represent the same compounds as in Table 1.

[0124] [Table 3]

[0125] [Table 4]

[0126] From the results in Tables 3 and 4, it was confirmed that even when drying was carried out by spray drying, the dissolution of the keralactone ester compounds was improved and the solubility of the solid formulation in water was also increased by heat-treating the preparation before drying.

[0127] (Test Example 3) [Preparation of prepared solution] A preparation solution was produced in the same manner as in Test Example 1, except that the excipient in Test Example 1 was changed to Pinedex #2 (Matsutani Chemical Industry Co., Ltd.).

[0128] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 80% by mass.

[0129] <Untreated product> The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0130] <Heated product 85> The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0131] <Autoclave product> The preparation was autoclaved (121°C, 1 minute). The autoclaved preparation was freeze-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "autoclaved product").

[0132] [evaluation] The dissolution and solubility of each preparation obtained in Test Example 3 were evaluated in the same manner as in Test Example 1. The results of dissolution are shown in Table 5, and the results of solubility are shown in Table 6. In Table 5, (1) to (6) in the column of kellactone ester compound content represent the same compounds as in Table 1.

[0133] [Table 5]

[0134] [Table 6]

[0135] From the results in Tables 5 and 6, it was confirmed that even when the type of excipient was changed, the dissolution of the keratinone ester compounds was improved and the solubility of the solid formulation in water was increased by heating the preparation solution before drying.

[0136] (Test Example 4) [Preparation of prepared solution] A preparation solution was produced in the same manner as in Test Example 1, except that the amount of excipient used was changed so that the content of the excipient in the preparation was 50% by mass or 60% by mass.

[0137] [Production of formulations] Each formulation was prepared as follows.

[0138] <Untreated product-A> The prepared solution was spray-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "untreated product-A"). The content of the excipient in the preparation was 50% by mass.

[0139] <Heated product 85-A> The preparation solution was heated at 85°C for 30 minutes. The heated preparation solution was spray-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "heated product 85-A"). The content of excipients in the preparation was 50% by mass.

[0140] <Untreated product-B> The prepared solution was spray-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "untreated product-B"). The content of the excipient in the preparation was 60% by mass.

[0141] <Heated product 85-B> The preparation was heated at 85°C for 30 minutes. The heated preparation was spray-dried to obtain a powdered solid preparation (hereinafter, sometimes referred to as "heated product 85-B"). The content of excipients in the preparation was 60% by mass.

[0142] [evaluation] The dissolution properties of each preparation obtained in Test Example 4 were evaluated in the same manner as in Test Example 1. The results are shown in Table 7. In Table 7, (1) to (6) in the column for the content of kerulactone ester compounds represent the same compounds as in Table 1.

[0143] [Table 7]

[0144] The results in Table 7 confirm that even when the amount of excipient is changed, the effects of the present invention can be obtained by heat-treating the preparation solution before drying.

[0145] (Test Example 5) <Test Example 5-1> [Preparation of prepared solution] 0.055 g of Hyuganin D and 4.945 g of an excipient (Cluster Dextrin (registered trademark), Glico Nutrition Foods Co., Ltd.) were dissolved in water to obtain a preparation solution.

[0146] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 99% by mass.

[0147] -Untreated- The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0148] -Heated product 85- The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0149] <Test Example 5-2> [Preparation of prepared solution] 0.07 g of cis-3'-acetyl-4'-tigloyl kerulactone and 4.93 g of an excipient (Cluster Dextrin (registered trademark), Glico Nutrition Foods Co., Ltd.) were dissolved in water to obtain a preparation solution.

[0150] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 99% by mass.

[0151] -Untreated- The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0152] -Heated product 85- The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0153] <Test Example 5-3> [Preparation of prepared solution] 0.25 g of poisedanocoumarin III and 4.75 g of an excipient (Cluster Dextrin (registered trademark), Glico Nutrition Foods Co., Ltd.) were dissolved in water to obtain a preparation solution.

[0154] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 95% by mass.

[0155] -Untreated- The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0156] -Heated product 85- The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0157] <Test Example 5-4> [Preparation of prepared solution] 0.095 g of isosamidin and 4.905 g of an excipient (Cluster Dextrin (registered trademark), Glico Nutrition Foods Co., Ltd.) were dissolved in water to obtain a preparation solution.

[0158] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 98% by mass.

[0159] -Untreated- The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0160] -Heated product 85- The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0161] <Test Example 5-5> [Preparation of prepared solution] 0.4 g of trans-3'-acetyl-4'-senecioyl kerulactone and 4.6 g of an excipient (cluster dextrin (registered trademark), Glico Nutrition Foods Co., Ltd.) were dissolved in water to obtain a preparation solution.

[0162] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 92% by mass.

[0163] -Untreated- The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0164] -Heated product 85- The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0165] <Test Example 5-6> [Preparation of prepared solution] 0.665 g of pteryxin and 4.335 g of an excipient (Cluster Dextrin (registered trademark), Glico Nutrition Foods Co., Ltd.) were dissolved in water to obtain a preparation solution.

[0166] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 87% by mass.

[0167] -Untreated- The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0168] -Heated product 85- The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0169] <Test Example 5-7> [Preparation of prepared solution] A total of 0.8 g of Hyuganin D, cis-3'-acetyl-4'-tigloylquellactone, poisedanocoumarin III, isosamidin, trans-3'-acetyl-4'-senecioylquellactone, and pteryxin, and 4.2 g of excipient (cluster dextrin (registered trademark), Glico Nutrition Foods Co., Ltd.) were dissolved in water to obtain a preparation solution.

[0170] [Production of formulations] Each formulation was produced as follows: The content of the excipient in each formulation was 84% ​​by mass.

[0171] -Untreated- The prepared solution was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as "untreated product").

[0172] -Heated product 85- The preparation was heated for 30 minutes at 85° C. The heated preparation was freeze-dried to obtain a powdery solid preparation (hereinafter, sometimes referred to as “heated product 85”).

[0173] <Evaluation> The dissolution properties of each preparation obtained in Test Example 5 were evaluated in the same manner as in Test Example 1. The results are shown in Tables 8 and 9. In Tables 8 and 9, (1) to (6) in the column for the content of kerulactone ester compounds represent the same compounds as in Table 1.

[0174] [Table 8]

[0175] [Table 9]

[0176] The results in Tables 8 and 9 also confirm that the effects of the present invention can be obtained by heat-treating the preparation liquid before drying.

[0177] (Combination example 1) Tablets having the following composition were prepared by a conventional method. Test Example 1 heated product 85 5.0mg Dolomite 83.4mg (Contains 20% calcium and 10% magnesium) Casein phosphopeptide 16.7mg Vitamin C 33.4mg Maltitol 136.8mg Collagen 12.7mg Sucrose fatty acid esters 12.0mg

[0178] (Combination example 2) An oral liquid preparation having the following composition was prepared by a conventional method. <Composition in 1 ampoule (100 mL)> Instantaneous heating product of Test Example 2 0.3% by mass Sorbitol 12.0% by mass Sodium benzoate 0.1% by mass · Fragrance 1.0% by mass Calcium sulfate 0.5% by mass · Purified water remainder

[0179] (Combination example 3) Granules having the following composition were produced by a conventional method. Autoclave product of Test Example 3 150.0 parts by mass Calcium 680.0 parts by mass Iron 6.8 parts by mass Beet oligosaccharides 1000.0 parts by mass Stevia extract 10.0 parts by mass

[0180] (Combination example 4) Soft capsules having the following composition were produced by a conventional method. 30 parts by weight of heated product 85-A from Test Example 4 200 parts by weight of olive oil Glycerin fatty acid ester 24 parts by mass Beeswax 24 parts by weight

[0181] (Combination example 5) Chocolate having the following composition was produced by a conventional method. 0.15 parts by mass of heated product 85-B of Test Example 4 Chocolate 45.0 parts by weight Sucrose 15.0 parts by mass Cocoa butter 20.0 parts by weight · Whole milk powder 25.0 parts by mass

[0182] (Combination example 6) A soft drink having the following composition was produced by a conventional method. Heated product 85 of Test Examples 5-7 0.3% by mass Royal jelly 1.0% by mass Water-soluble collagen 10.0% by mass Job's tears extract 1.0% by mass Korean ginseng extract 1.0% by mass Oligosaccharides 5.0% by mass Sucrose 10.0% by mass Prune juice 2.0% by mass Pomegranate juice 5.0% by mass Grapefruit juice 10.0% by mass Grapefruit flavor 0.7% by mass · Water remainder · Total 100.0% by mass

Claims

1. A solid composition containing a kellactone ester compound, which contains a kellactone ester compound and an excipient, A solid composition containing a kellactone ester compound, characterized in that the content of the kellactone ester compound in the solid composition containing a kellactone ester compound, calculated from the sample solution prepared in the following process 2, is 85 mass% or more, when the content of the kellactone ester compound in the solid composition containing a kellactone ester compound, calculated from the sample solution prepared in the following process 1, is taken as 100 mass%. <Process 1> 250 to 750 mg of the solid composition containing kellactone ester compounds is weighed out and suspended in 8 mL of water. 1 g of diatomaceous earth is added as a filter aid and suspended in the suspension. 12 mL of methanol is then added and the mixture is stirred at 40°C for 5 minutes to form a suspension. The suspension is filtered through diatomaceous earth, the resulting filtrate is mixed with 4 mL of water, and the volume is adjusted to 50 mL with 50% by volume of methanol to prepare a sample solution. <Process 2> Weigh out 250 to 750 mg of the solid composition containing kellactone ester compounds, add 10 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 10 mL of methanol, and stir at room temperature to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is adjusted to a constant volume of 50 mL with 50% by volume methanol to prepare a sample solution.

2. The solid composition containing a kellactone ester compound according to claim 1, wherein the kellactone ester compound is at least one selected from the group consisting of hyuganin D, cis-3'-acetyl-4'-tigloyl kellactone, poisedanocoumarin III, isosamidin, trans-3'-acetyl-4'-senecioyl kellactone, and pteryxin.

3. 3. The solid composition containing kellactone ester compounds according to claim 1, wherein the kellactone ester compounds are contained in a plant extract.

4. 4. The solid composition containing kellactone ester compounds according to claim 3, wherein the plant is Choumeisou.

5. A method for producing a solid composition containing a kellactone ester compound, the solid composition containing a kellactone ester compound and an excipient, comprising: preparing a liquid composition containing the kerulactone ester compound and the excipient; heating the liquid composition to a temperature of 85°C or higher; and drying the liquid composition after heating.

6. The method for producing a solid composition containing a kellactone ester compound according to claim 5, wherein the kellactone ester compound is at least one selected from the group consisting of hyuganin D, cis-3'-acetyl-4'-tigloyl kellactone, poisedanocoumarin III, isosamidin, trans-3'-acetyl-4'-senecioyl kellactone, and pteryxin.

7. 7. The method for producing a solid composition containing a kellactone ester compound according to claim 5, wherein the kellactone ester compound is contained in a plant extract.

8. 8. The method for producing a solid composition containing a kerulactone ester compound according to claim 7, wherein the plant is Choumeisou.

9. 7. The method for producing a solid composition containing a kellactone ester compound according to claim 5 or 6, wherein the content of the kellactone ester compound in the solid composition containing a kellactone ester compound, calculated from the sample solution prepared in the following process 2, is 85% by mass or more, when the content of the kellactone ester compound in the solid composition containing a kellactone ester compound, calculated from the sample solution prepared in the following process 1, is taken as 100% by mass. <Process 1> 250 to 750 mg of the solid composition containing kellactone ester compounds is weighed out and suspended in 8 mL of water. 1 g of diatomaceous earth is added as a filter aid and suspended in the suspension. 12 mL of methanol is then added and the mixture is stirred at 40°C for 5 minutes to form a suspension. The suspension is filtered through diatomaceous earth, the resulting filtrate is mixed with 4 mL of water, and the volume is adjusted to 50 mL with 50% by volume of methanol to prepare a sample solution. <Process 2> Weigh out 250 to 750 mg of the solid composition containing kellactone ester compounds, add 10 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 10 mL of methanol, and stir at room temperature to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is adjusted to a constant volume of 50 mL with 50% by volume methanol to prepare a sample solution.

10. A method for improving the quality of a solid composition containing a kellactone ester compound, the solid composition containing a kellactone ester compound and an excipient, comprising: preparing a liquid composition containing the kerulactone ester compound and the excipient; heating the liquid composition to a temperature of 85°C or higher; and drying the liquid composition after the heating. A method for improving the quality of a solid composition containing a kellactone ester compound, wherein the quality improvement of the solid composition containing a kellactone ester compound comprises improving the elution property of the kellactone ester compound.

11. The method for improving the quality of a solid composition containing a kellactone ester compound according to claim 10, wherein the kellactone ester compound is at least one selected from the group consisting of hyuganin D, cis-3'-acetyl-4'-tigloyl kellactone, poisedanocoumarin III, isosamidin, trans-3'-acetyl-4'-senecioyl kellactone, and pteryxin.

12. 12. The method for improving the quality of a solid composition containing a kellactone ester compound according to claim 10 or 11, wherein the kellactone ester compound is contained in a plant extract.

13. 13. The method for improving the quality of a solid composition containing a kerulactone ester compound according to claim 12, wherein the plant is Choumeisou.

14. 12. The method for improving the quality of a solid composition containing a kellactone ester compound according to claim 10 or 11, wherein the quality improvement of the solid composition containing a kellactone ester compound includes improving the solubility of the solid composition containing a kellactone ester compound in water.

15. 12. A method for improving the quality of a solid composition containing a kellactone ester compound according to claim 10 or 11, wherein the content of the kellactone ester compound in the solid composition containing a kellactone ester compound, calculated from a sample solution prepared in the following process 2, is 85% by mass or more, when the content of the kellactone ester compound in the solid composition containing a kellactone ester compound, calculated from a sample solution prepared in the following process 1, is taken as 100% by mass. <Process 1> 250 to 750 mg of the solid composition containing kellactone ester compounds is weighed out and suspended in 8 mL of water. 1 g of diatomaceous earth is added as a filter aid and suspended in the suspension. 12 mL of methanol is then added and the mixture is stirred at 40°C for 5 minutes to form a suspension. The suspension is filtered through diatomaceous earth, the resulting filtrate is mixed with 4 mL of water, and the volume is adjusted to 50 mL with 50% by volume of methanol to prepare a sample solution. <Process 2> Weigh out 250 to 750 mg of the solid composition containing kellactone ester compounds, add 10 mL of water, and suspend. Add 1 g of diatomaceous earth as a filter aid, and suspend. Next, add 10 mL of methanol, and stir at room temperature to form a suspension. The suspension is filtered through diatomaceous earth, and the resulting filtrate is adjusted to a constant volume of 50 mL with 50% by volume methanol to prepare a sample solution.

16. 3. An oral composition comprising the solid composition containing a kerulactone ester compound according to claim 1.

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