Glycyrrhizic acid-containing composition

Abstract

To develop materials that effectively produce anti-inflammatory effects. [Solution] A composition containing glycyrrhizic acid, liquiritin, and isoliquiritin, The mass ratio of glycyrrhizic acid to liquiritin (glycyrrhizic acid:liquiritin) is 1:0.3 to 2. The mass ratio of glycyrrhizic acid to isoliquiritin (glycyrrhizic acid:isoliquiritin) is 1:0.5 to 3. composition.

Description

Technical Field

[0001] The present disclosure relates to a composition containing components such as glycyrrhizic acid, and more particularly to a composition containing glycyrrhizic acid, liquiritin, and isoliquiritin. Note that the content of all documents described in this specification is incorporated herein by reference.

Background Art

[0002] Inflammation suppression is an effect required in various fields. Many components and compositions have been developed as materials for inflammation suppression. For example, licorice (Glycyrrhiza genus), a perennial plant of the legume family, is known to have an anti-inflammatory effect.

[0003] Licorice is a perennial plant of the legume family that grows wild in arid regions such as southern Russia, Mongolia, northern to western China, and Europe. Licorice is particularly known as an important raw material in traditional Chinese medicine and has been used since ancient times as an analgesic, antispasmodic, antitussive, and expectorant.

[0004] In addition to glycyrrhizic acid, licorice contains licorice flavonoids such as liquiritin and isoliquiritin. Extracts from licorice containing these components are used in various applications in addition to pharmaceutical additives.

[0005] For example, Patent Document 1 describes using a licorice extract containing glycyrrhizic acid, liquiritin, licuritigenin, etc. as a feed additive for livestock. Further, Patent Document 2 describes using a hydroalcoholic extract of licorice containing these three components, etc. as a melanogenesis inhibitor and an MMP1 inhibitor.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

[0007] [Non-Patent Document 1] Tokyo University of Agriculture, Journal of Agriculture, Vol. 55, No. 1, pp. 63-72, "Vegetation Survey and Soil Moisture Estimation Using Pattern Development Method in Mongolian Grasslands" [Non-Patent Document 2] Shi et al., Afr J Tradit Complement Altern Med. (2014) 11(2):334-338 [Non-Patent Document 3] Biochemical and Biophysical Research Communications 467 (2015) 447-450 [Non-Patent Document 4] C.-j. Ma et al. / J. Chromatogr. A 1078 (2005) 188-192 [Non-Patent Document 5] Int. J. Mol. Sci. 2021, 22, 876 [Overview of the project] [Problems that the invention aims to solve]

[0008] The inventors of this invention conducted research with the aim of developing a material that effectively exhibits anti-inflammatory effects. [Means for solving the problem]

[0009] While diligently studying licorice extract, the inventors discovered the possibility that a composition containing specific components in specific proportions may have particularly excellent anti-inflammatory effects, and further refined the composition.

[0010] This disclosure includes, for example, the following subjects: Section 1. A composition containing glycyrrhizic acid, liquiritin, and isoliquiritin, The mass ratio of glycyrrhizic acid to liquiritin (glycyrrhizic acid:liquiritin) is 1:0.3 to 2. The mass ratio of glycyrrhizic acid to isoliquiritin (glycyrrhizic acid:isoliquiritin) is 1:0.5 to 3. composition. Section 2. The mass ratio of glycyrrhizic acid to isoliquiritin (glycyrrhizic acid:isoliquiritin) is 1:1.4 to 3. The composition described in item 1. Section 3. When the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, the total amount of glycyrrhizic acid, liquiritin, and isoliquiritin is 75 to 95 parts by mass. The composition described in item 1 or 2. Section 4. When the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, the amount of glycyrrhizic acid is 1 to 50 parts by mass (preferably 15 to 35 parts by mass). A composition as described in any of items 1 to 3. Section 5. When the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, isoliquiritin is present in 37 to 50 parts by mass. A composition as described in any of items 1 to 4. Section 6. Furthermore, the composition according to any one of claims 1 to 5 contains ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicumarin. Section 7. A composition according to any one of items 1 to 6, which is water or aqueous ethanol extract of licorice. Item 8. The composition according to any one of Items 1 to 7, which is a composition for anti - inflammation. Item 9. The composition according to any one of Items 1 to 7, which is a composition for anti - allergy. Item 10. An external preparation containing the composition according to any one of Claims 1 to 9. Item 11. The external preparation according to Item 10, which is a cosmetic or an external medicine. [[ID=???]]

Advantages of the Invention

[0011] A novel composition having an excellent anti - inflammatory effect is provided. Further, the novel composition can also exhibit an excellent anti - allergy effect.

Brief Description of the Drawings

[0012] [Figure 1] Examples of the variation of the soil moisture content (moisture ratio [volume%]) when the soil moisture content in the field is managed in licorice cultivation are shown.

Modes for Carrying Out the Invention

[0013] Hereinafter, each embodiment included in the present disclosure will be described in more detail. The present disclosure preferably includes, but is not limited to, compositions containing glycyrrhizic acid, liquiritin, and isoliquiritin in specific ratios, their uses, and their manufacturing methods, etc. The present disclosure includes all that is disclosed in this specification and can be recognized by those skilled in the art.

[0014] <; The composition included in the present disclosure contains glycyrrhizic acid, liquiritin, and isoliquiritin. This composition may be referred to as the composition of the present disclosure.

[0015] In the compositions of this disclosure, glycyrrhizic acid and liquiritin are contained in a mass ratio (glycyrrhizic acid:liquiritin) of 1:0.3 to 2. The upper or lower limit of this range (0.3 to 2) may be, for example, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, or 1.9. For example, the range may be 0.4 to 1.7 or 0.5 to 1.5.

[0016] In the compositions of this disclosure, glycyrrhizic acid and isoliquiritin are contained in a mass ratio (glycyrrhizic acid:isoliquiritin) of 1:0.5 to 3. The upper or lower limit of this range (0.5 to 3) may be, for example, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, or 2.9. For example, the range may be 0.8 to 2.7 or 1 to 2.5. In particular, the range is more preferably 1.4 to 3, even more preferably 1.5 to 2.7, and still more preferably 1.5 to 2.5.

[0017] The compositions of the present disclosure preferably further contain at least one selected from the group consisting of ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicumarin, more preferably two, three, or four of these, and even more preferably all of these.

[0018] If the composition of this disclosure contains ononine, it is preferable that glycyrrhizic acid and ononine are contained in a mass ratio (glycyrrhizic acid:ononine) of 1:0.05 to 0.5. The upper or lower limit of this range (0.05 to 0.5) may be, for example, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, or 0.45. For example, it is more preferable that the range be 0.1 to 0.4.

[0019] If the composition of this disclosure contains liquiritigenin, it is preferable that glycyrrhizic acid and liquiritigenin are contained in a mass ratio (glycyrrhizic acid:liquiritigenin) of 1:0.01 to 0.3. The upper or lower limit of this range (0.01 to 0.3) may be, for example, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, or 0.29. For example, it is more preferable that the range is 0.02 to 0.25.

[0020] If the composition of this disclosure contains isoliquiritigenin, it is preferable that glycyrrhizic acid and isoliquiritigenin are contained in a mass ratio (glycyrrhizic acid:isoliquiritigenin) of 1:0.005 to 0.2. The upper or lower limit of this range (0.005 to 0.2) may be, for example, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, or 0.19. For example, it is more preferable that the range is 0.006 to 0.1.

[0021] If the composition of this disclosure contains formononetin, it is preferable that glycyrrhizic acid and formononetin are contained in a mass ratio (glycyrrhizic acid:formononetin) of 1:0.005 to 0.2. The upper or lower limit of this range (0.005 to 0.2) may be, for example, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, or 0.19. For example, it is more preferable that the range is 0.006 to 0.1.

[0022] If the composition of this disclosure contains glycicoumarin, it is preferable that glycyrrhizic acid and glycicoumarin are contained in a mass ratio (glycyrrhizic acid:glycicoumarin) of 1:0.005 to 0.2. The upper or lower limit of this range (0.005 to 0.2) may be, for example, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, or 0.19. For example, it is more preferable that the range be 0.006 to 0.15.

[0023] Furthermore, in the composition of this disclosure, when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, it is preferable that the total amount of glycyrrhizic acid, liquiritin, and isoliquiritin is 75 to 95 parts by mass. The upper or lower limit of this range may be, for example, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, or 94 parts by mass. The range may be, for example, 80 to 95 parts by mass, 85 to 95 parts by mass, or 85 to 94 parts by mass.

[0024] Furthermore, in the compositions of this disclosure, it is preferable that the amount of glycyrrhizic acid is 1 to 50 parts by mass when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass. The upper or lower limit of this range may be, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, or 49 parts by mass. The range may be, for example, 5 to 45 parts by mass or 10 to 40 parts by mass. Furthermore, the range is particularly preferably 15 to 35 parts by mass, but may also be 16 to 34 parts by mass, 18 to 32 parts by mass, or 20 to 30 parts by mass.

[0025] Furthermore, in the composition of this disclosure, when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, it is preferable that liquiritin is present in an amount of 15 to 35 parts by mass. The upper or lower limit of this range may be, for example, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, or 34 parts by mass. The range may be, for example, 16 to 34 parts by mass, 18 to 32 parts by mass, or 20 to 30 parts by mass.

[0026] Furthermore, in the composition of this disclosure, when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, isoliquiritin is preferably 30 to 50 parts by mass. The upper or lower limit of this range may be, for example, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, or 49 parts by mass. The range may be, for example, 31 to 49 parts by mass, or 12 to 48 parts by mass. It is more preferable that the range be 37 to 50 parts by mass, and even more preferable that be 40 to 50 parts by mass.

[0027] Furthermore, in the composition of this disclosure, when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, it is preferable that ononine is 1 to 10 parts by mass. The upper or lower limit of this range may be, for example, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, or 9.5 parts by mass. The range may be, for example, 2 to 9 parts by mass or 3 to 7 parts by mass.

[0028] Furthermore, in the composition of this disclosure, when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, it is preferable that liquiritigenin is present in an amount of 0.5 to 5 parts by mass. The upper or lower limit of this range may be, for example, 1, 1.5, 2, 2.5, 3, 3.5, 4, or 4.5 parts by mass. The range may also be, for example, 1 to 4 parts by mass.

[0029] Furthermore, in the composition of this disclosure, when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, isoliquiritigenin is preferably 0.05 to 1 part by mass. The upper or lower limit of this range may be, for example, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, or 0.95 parts by mass. The range may be, for example, 0.1 to 0.9 parts by mass, or 0.15 to 0.5 parts by mass.

[0030] Furthermore, in the composition of this disclosure, when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, it is preferable that formononetin is present in an amount of 0.05 to 2 parts by mass. The upper or lower limit of the range may be, for example, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, or 1.95 parts by mass. The range may also be, for example, 0.1 to 1.8 parts by mass, or 0.2 to 1.5 parts by mass.

[0031] Furthermore, in the composition of this disclosure, it is preferable that when the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin contained is 100 parts by mass, the amount of glycicoumarin is 0.05 to 5 parts by mass. The upper or lower limit of the range may be, for example, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, or 4.9 parts by mass. The range may be, for example, 0.1 to 4.5 parts by mass, or 0.2 to 4 parts by mass.

[0032] In the compositions of this disclosure, the total amount of glycyrrhizic acid, liquiritin, and isoliquiritin is preferably, for example, 0.2 to 95% by mass. The upper or lower limit of this range is, for example, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 4 The mass percentages may be 8, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, or 94%. The range may be, for example, 0.5 to 90% by mass.

[0033] In the compositions of this disclosure, glycyrrhizic acid is preferably contained in an amount of 0.1 to 50% by mass, although this is not particularly limited. The upper or lower limit of this range may be, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, or 49% by mass. The range may be, for example, 0.2 to 49 mass%, 0.5 to 48 mass%, 1 to 47 mass%, 5 to 45 mass%, or 10 to 40 mass%. Alternatively, the range may be 15 to 35 mass%, 16 to 34 mass%, 18 to 32 mass%, or 20 to 30 mass%. For example, if the range is 0.1 to 4 mass%, the upper or lower limit of the range (0.1 to 4 mass%) may be, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, or 3.9 mass%. The range (0.1 to 4 mass%) may also be, for example, 1 to 4 mass% or 1.2 to 3.8 mass%, 1.5 to 3.5 mass%, or 1.8 to 3.2 mass%. It should be noted, though obvious, that glycyrrhizic acid is particularly preferable to satisfy the above-mentioned mass ratio range and content (mass%). It is also preferable that all of the requirements described herein are met when combined. The same applies to the other components (liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicumarin).

[0034] In the compositions of this disclosure, although not particularly limited, liquiritin is preferably contained in an amount of 0.03 to 15% by mass, and more preferably in an amount of 0.03 to 4% by mass. The upper or lower limits of the range may be, for example, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14% by mass. The range may be, for example, 1 to 4% by mass, or 1.2 to 3.8% by mass, or 1.5 to 3.5% by mass, or 1.7 to 3.2% by mass.

[0035] In the compositions of this disclosure, isoliquiritin is preferably contained in an amount of 0.05 to 25% by mass, and more preferably in an amount of 0.05 to 7% by mass. The upper or lower limits of this range are, for example, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, The mass may be 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24%. The range may be, for example, 1.5 to 7% by mass, or 1.7 to 6.8% by mass, or 1.5 to 6.5% by mass, or 2 to 6.5% by mass.

[0036] In the compositions of this disclosure, although not particularly limited, ononine is preferably contained in an amount of 0 to 1% by mass. That is, it is preferable that ononine is not contained or is contained in an amount of 1% by mass or less. The lower limit when ononine is contained is not particularly limited, but for example, 0.01% by mass is an example. The upper or lower limit of this range (0 to 1% by mass) may be, for example, 0.01, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, or 0.95% by mass. This range may be, for example, 0.1 to 0.9% by mass, or 0.2 to 0.8% by mass.

[0037] In the compositions of this disclosure, liquiritigenin is preferably contained in an amount of 0 to 0.5% by mass, although this is not particularly limited. That is, it is preferable that liquiritigenin is not contained or is contained in an amount of 0.5% by mass or less. The lower limit when liquiritigenin is contained is not particularly limited, but for example, it is 0.01% by mass. The upper or lower limit of this range (0 to 0.5% by mass) may be, for example, 0.01, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, or 0.45% by mass. This range may be, for example, 0.1 to 0.4% by mass.

[0038] In the compositions of this disclosure, isoliquiritigenin is preferably contained in an amount of 0 to 0.1% by mass, although this is not particularly limited. That is, isoliquiritigenin is preferably not contained or contained in an amount of 0.1% by mass or less. The lower limit when it is contained is not particularly limited, but for example, it is 0.001% by mass. The upper or lower limit of this range (0 to 0.1% by mass) may be, for example, 0.001, 0.005, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, or 0.09% by mass. This range may be, for example, 0.001 to 0.09% by mass, or 0.005 to 0.08% by mass. In particular, 0.03 to 0.09% by mass or 0.04 to 0.08% by mass are more preferred.

[0039] In the compositions of this disclosure, formononetin is preferably contained in an amount of 0 to 0.5% by mass, although this is not particularly limited. That is, formononetin is preferably not contained or contained in an amount of 0.5% by mass or less. The lower limit when formononetin is contained is not particularly limited, but for example, it is 0.01% by mass. The upper or lower limit of this range (0 to 0.5% by mass) may be, for example, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, or 0.45% by mass. This range may be, for example, 0.01 to 0.3% by mass.

[0040] In the compositions of this disclosure, glycicoumarin is preferably contained in an amount of 0 to 0.5% by mass, although this is not particularly limited. That is, it is preferable that glycicoumarin is not contained or is contained in an amount of 0.5% by mass or less. The lower limit when it is contained is not particularly limited, but for example, it is 0.01% by mass. The upper or lower limit of this range (0 to 0.5% by mass) may be, for example, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, or 0.45% by mass. This range may be, for example, 0.01 to 0.4% by mass.

[0041] The content and proportion of each component in the composition of this disclosure are measured by HPLC (High Performance Liquid Chromatography) using an ODS column (after dissolving them in water or a suitable solvent such as an organic solvent, if necessary). More specifically, they are measured by HPLC under the following conditions.

[0042] [Device] Waters Alliance 2695 HPLC System [column] Tosoh TSKgel ODS-100V (4.6 x 150 mm, 3 μm) [Mobile phase] Solution A: 28% acetonitrile aqueous solution (containing 50 mM ammonium acetate and 0.5% acetic acid) Solution B: Acetonitrile [mode] Gradient (16 minutes → 22 minutes, and 27 minutes → 27.5 minutes)

[0043] [Table 1A]

[0044] [Flow rate] 1.3 mL / min [Column temperature] 40℃ [Injection amount] 10 μL [measurement] 254nm, 350nm Glycyrrhizic acid, liquiritin, ononine, liquiritigenin, and formononetin are detected at 254 nm, while isoliquiritin, isoliquiritigenin, and glycicoumarin are detected at 350 nm. However, since the peak of formononetin overlaps with that of isoliquiritigenin at 254 nm detection, the area value corrected using the following correction formula is used.

[0045] Correction formula Formononetin-corrected area value = Formononetin-peak area value -(Isoliquiritigenin peak area value) (*Isoliquiritigenin area ratio) *Isoliquiritigenin area ratio: Area values ​​at 254 nm / 350 nm for isoliquiritigenin preparations

[0046] The compositions of this disclosure can be prepared, for example, by mixing each component with a solvent as needed. Each component may be, for example, a synthetic product, or may be extracted from plants or animals (especially licorice) and, if necessary, purified. Synthesis can be carried out by known methods or methods that can be easily conceived from known methods. In addition, each component may be purchased commercially and used. As a solvent, water or aqueous alcohol (especially aqueous ethanol) is preferred. As aqueous ethanol, for example, 0 to 50% by mass ethanol (preferably 10 to 40% by mass ethanol, more preferably 20 to 40% by mass ethanol) can be used. In addition, when using licorice, either Glycyrrhiza uralensis Fisher or Glycyrrhiza glabra Linne can be used. In particular, licorice grown in Hokkaido is preferred. In addition, it is preferable to use the root portion of licorice in particular.

[0047] Furthermore, when using licorice for extraction, it is preferable that the licorice be grown in soil where the soil moisture content of the field is preferably 5-60% by volume, more preferably 10-50% by volume, during the period of abundant above-ground growth (especially July to September). It is also preferable to artificially manage the soil moisture content to achieve this level. When grown in soil with such a soil moisture content, the composition of each component contained in the resulting licorice extract may be particularly preferable for use in the compositions of this disclosure.

[0048] Furthermore, since each component contained in the composition of this disclosure is contained in licorice extract, it is also preferable to use licorice extract, or a licorice extract prepared by, for example, concentrating it, or removing or adding components to adjust the amount of each component as appropriate, as the composition of this disclosure. As the licorice extract, a water or aqueous alcohol (particularly aqueous ethanol) extract of licorice is preferred. As the aqueous ethanol, for example, there is ethanol with a concentration of more than 0 to 50% by mass (preferably 10 to 40% by mass, more preferably 20 to 40% by mass).

[0049] For extraction, known extraction methods can be used. For example, licorice (especially the roots) can be ground while adding water, and then extracted with a solvent. Heating may be used as appropriate during extraction.

[0050] The compositions of this disclosure are not particularly limited, but preferably have a Brix value of 25 or higher. The upper limit is not particularly limited, but for example, it is 30. The range (25-30) may be, for example, 25-27 or 25-26. If the composition of this disclosure is a licorice extract, it is also preferable that it is concentrated until the Brix value reaches 25 or higher.

[0051] The compositions disclosed herein preferably exhibit excellent anti-inflammatory effects. In particular, the compositions disclosed herein preferably have the effect of suppressing nitric oxide (NO) production in cells, thereby exhibiting excellent anti-inflammatory effects.

[0052] Furthermore, the compositions of this disclosure also preferably exhibit excellent anti-allergic effects. In particular, the compositions of this disclosure preferably have the effect of suppressing granule release, i.e., degranulation (especially degranulation caused by cross-linking of IgE by an antigen) in granule-releasing cells (e.g., basophils, neutrophils, eosinophils, mast cells), thereby exhibiting excellent anti-allergic effects.

[0053] Because these effects are desirable, the compositions of this disclosure can be preferably used, for example, as anti-inflammatory or anti-allergic compositions.

[0054] Furthermore, the compositions of this disclosure can preferably be used by adding them to topical preparations. Topical preparations containing the compositions of this disclosure are also preferably included in this disclosure. Such topical preparations are not particularly limited, but preferably include cosmetics or topical pharmaceuticals. Such topical preparations may further contain known components used in topical preparations. Examples of such components include water, oils, surfactants, humectants, higher alcohols, metal ion chelating agents, natural and synthetic polymers, water-soluble and oil-soluble polymers, UV shielding agents, various extracts, colorants such as organic dyes, preservatives, antioxidants, pigments, thickeners, pH adjusters, fragrances, cooling agents, antiperspirants, bactericides, skin activators, and various powders. The amounts of these components can also be appropriately set based on information on the amounts used in known topical preparations. There are no particular limitations, but for example, the amounts may be about 1 to 99.9% by mass, or about 50 to 99.9% by mass.

[0055] In this specification, the term "comprising" includes both "consisting essentially of" and "consisting of." Furthermore, this disclosure encompasses all combinations of the constituent elements described herein.

[0056] Furthermore, the various characteristics (properties, structure, function, etc.) described in each embodiment of this disclosure above may be combined in any way to identify the subject matter covered by this disclosure. In other words, this disclosure covers all subject matter consisting of any combination of the combinable characteristics described herein. [Examples]

[0057] The embodiments of this disclosure will be described in more detail below with examples, but the embodiments of this disclosure are not limited to the examples below.

[0058] Cultivation of licorice In a field in Hokkaido, licorice was planted in July and harvested in October of the following year. In this cultivation, soil moisture content was managed from July to September, when the above-ground parts were lush. The field's soil moisture content was managed to be between 5.0% by volume and 60.0% by volume (preferably between 10.0% by volume and 50.0% by volume). Specifically, when soil moisture content became low, irrigation was carried out using irrigation tubes to suppress the decrease in soil moisture. When soil moisture content became high, agricultural paper mulch was installed to reduce water infiltration into the soil while ensuring water evaporation from the soil, thereby suppressing the rise in soil moisture. Furthermore, to manage soil moisture content, open ditches were installed around the field in advance to prevent the soil moisture content from rising.

[0059] Figure 1 shows an example of soil moisture content (moisture percentage [volume %]) fluctuations when the soil moisture content of a field was actually managed. (Figure 1 shows the soil moisture content of two fields, Field A and Field B.) In this example, the soil moisture content was managed to be between 10.2 volume% and 46.7 volume%. The soil moisture content was measured using a METER 5TE soil moisture, temperature, and EC sensor.

[0060] Manufacturing of licorice extract Extracts were prepared using licorice cultivated as described above (see Production Examples 1 and 2 below). Extracts were also prepared using licorice purchased from China (see Production Examples 3 and 4 below). In Mongolia, the native habitat of licorice, soil moisture content is often between 0% and 10%, and in most places it is reported to be below 15% (see Non-Patent Literature 1 above: Tokyo University of Agriculture Agricultural Bulletin, Vol. 55, No. 1, pp. 63-72). Assuming a soil specific gravity of 1.2 g / mL, when soil moisture content is calculated, a moisture content of 10% corresponds to approximately 7 volume%, indicating that the soil is very dry. It is presumed that the purchased licorice from China was cultivated in soil with a similar soil moisture content.

[0061] (Manufacturing Example 1) Production of licorice extract from Hokkaido (hot water extraction) Licorice roots, planted in July in a field in Hokkaido and harvested in October of the following year, were washed, dried, and cut into 5mm wide strips. 3kg of the resulting licorice root strips were ground in a muscoloider (stone mill) with added water (3000rpm, stone clearance 1mm). The ground material was placed in a 100L jacketed beaker, and extracted by stirring for 30 minutes with 60L of water while steam heating. After extraction, the extract was packed into a filter cloth and pressed using a press until the filtrate was completely drained. 58L of the obtained filtrate was concentrated under reduced pressure using a small evaporator until the Brix reached 25 or higher to obtain licorice extract. This is sometimes referred to as extract 1.

[0062] The components of extract 1 were quantified by high-performance liquid chromatography (HPLC). The results showed that it contained 21.05 mg / g of glycyrrhizic acid, 19.05 mg / g of liquiritin, and 25.38 mg / g of isoliquiritin. (See Table 2 for the content of other flavonoids measured.)

[0063] (Manufacturing Example 2) Production of licorice extract from Hokkaido (30% ethanol extraction) Licorice roots, planted in July in a field in Hokkaido and harvested in October of the following year, were washed, dried, and cut into 5mm wide strips. The resulting licorice root strips were ground in a muscoloider (stone mill) with added water (3000 rpm, stone clearance 1mm). The ground material was placed in a 100L jacketed beaker, and 18.9L of 95% ethanol was added to 41.0L of water. The mixture was stirred and extracted for 30 minutes while being heated with steam. After the extraction process, the extract was packed into a filter cloth and pressed using a press until the filtrate was completely drained. The obtained 56L of filtrate was concentrated under reduced pressure in a small evaporator until the Brix reached 25 or higher to obtain licorice extract. This is sometimes referred to as extract 2.

[0064] HPLC analysis of the components of extract 2 revealed that it contained 28.08 mg / g of glycyrrhizic acid, 28.32 mg / g of liquiritin, and 60.86 mg / g of isoliquiritin. (See Table 2 for the measured flavonoid content.)

[0065] (Manufacturing Example 3) Manufacturing of licorice extract (hot water extraction) from overseas Purchased Chinese licorice root fragments were ground in a muscoloider with added water (3000 rpm, 1 mm stone clearance). The ground material was placed in a 100 L jacketed beaker, and 60 L of water was added. The material was stirred and extracted for 30 minutes while being heated with steam. After extraction, the extract was packed into a filter cloth and pressed using a press until the filtrate was completely drained. The obtained 60 L of filtrate was concentrated under reduced pressure in a small evaporator until the Brix reached 25 or higher to obtain licorice extract. This is sometimes referred to as extract 3.

[0066] HPLC analysis of the components of extract 3 revealed that it contained 72.44 mg / g of glycyrrhizic acid, 5.00 mg / g of liquiritin, and 5.94 mg / g of isoliquiritin. (See Table 2 for the content of other flavonoids measured.)

[0067] (Manufacturing Example 4) Manufacturing of licorice extract from overseas (30% ethanol extraction) Purchased Chinese licorice root flakes were ground in a muscoloider with added water (3000 rpm, stone clearance 1 mm). The ground material was placed in a 100 L jacketed beaker, and 18.9 L of 95% ethanol was added to 41.0 L of water. The mixture was stirred and extracted for 30 minutes while being heated with steam. After extraction, the extract was packed into a filter cloth and pressed using a press until the filtrate was completely drained. The obtained 55 L of filtrate was concentrated under reduced pressure in a small evaporator until the Brix reached 25 or higher to obtain licorice extract. This is sometimes referred to as extract 4.

[0068] HPLC analysis of the components of extract 4 revealed that it contained 96.88 mg / g of glycyrrhizic acid, 4.38 mg / g of liquiritin, and 6.62 mg / g of isoliquiritin. (See Table 2 for the content of other flavonoids measured.)

[0069] Quantitative analysis by HPLC was performed as follows: Approximately 50 mg of the obtained licorice extract (extract 1, 2, 3, or 4) was accurately weighed, 7 mL of 50% ethanol was added, and extraction was performed at 45°C for 30 minutes with appropriate stirring. The supernatant was collected by centrifugation, and 5 mL of 50% ethanol was added again for extraction. After centrifugation, the supernatants were combined, made up to 15 mL, and filtered to obtain the quantitative analysis sample. The substances to be quantified were eight components: glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoiquiritigenin, formononetin, and glycicoumarin. All eight components were quantified using a single-check counting curve. Glycyrrhizic acid, liquiritin, ononine, liquiritigenin, and formononetin were detected at 254 nm, while isoliquiritin, isoliquiritigenin, and glycicoumarin were detected at 350 nm. Since formononetin's peak overlaps with isoliquiritigenin's peak at 254nm detection, the area value corrected using the following correction formula was used.

[0070] Correction formula Formononetin-corrected area value = Formononetin-peak area value -(Isoliquiritigenin peak area value) (*Isoliquiritigenin area ratio) *Isoliquiritigenin area ratio: Area values ​​at 254 nm / 350 nm for isoliquiritigenin preparations

[0071] The analysis was performed using the following equipment and conditions. [Device] Waters Alliance 2695 HPLC System [column] Tosoh TSKgel ODS-100V (4.6 x 150 mm, 3 μm) [Mobile phase] Solution A: 28% acetonitrile aqueous solution (containing 50 mM ammonium acetate and 0.5% acetic acid) Solution B: Acetonitrile [mode] Gradient (16 minutes → 22 minutes, and 27 minutes → 27.5 minutes)

[0072] [Table 1B]

[0073] [Flow rate] 1.3 mL / min [Column temperature] 40℃ [Injection amount] 10 μL [measurement] 254nm, 350nm

[0074] The results are summarized in the table below.

[0075] [Table 2]

[0076] Measurement of the anti-inflammatory effect of licorice extract The anti-inflammatory effects of the prepared licorice extracts 1-4 were measured. The nitric oxide (NO) production rate (%) was measured, and the anti-inflammatory effect was evaluated by its inhibitory effect. More specifically, the procedure was as follows. (Test method) Mouse macrophage-like cell line RAW264 (hereinafter abbreviated as "RAW264 cells") was seeded in 96-well plates, and a culture medium containing lipopolysaccharide (LPS) (final concentration 0.1 μg / mL) was added. Each licorice extract was then added to a final concentration of 1000 μg / mL. A control group was prepared by adding only the culture medium and performing the same procedure. A sample blank was prepared by adding culture medium without RAW264 cells and performing the same procedure. After incubating overnight at 37°C, the cell supernatant was separated into another plate. Griess reagent was added to the cell supernatant and incubated at 37°C for 20 minutes. (Measurement method) The absorbance of azo compounds produced by the diazo coupling reaction of NO2 ions and Griess reagent was measured using a microplate reader. (Measurement wavelength: 540 nm, n=3) (Calculation method) Absorbance was measured using a NaNO2 solution as a standard solution, and a calibration curve was created. The NO2 concentration (μmol / L) was calculated from the absorbance of each well using the calibration curve. In this calculation, the absorbance used in the calibration curve was the absorbance of the measurement well minus the absorbance of the sample blank well.

[0077] The NO production rate was calculated using the following formula.

[0078] NO production rate (%) = {(Average NO2 concentration [Sa]) / (Average NO2 concentration [CN])} × 100 NO2 concentration [Sa]: NO2 concentration of each test solution NO2 concentration [CN]: NO2 degree of comparison

[0079] (Test results) The NO production rate (%) for each licorice extract is shown in the table below.

[0080] [Table 3]

[0081] All extracts were found to suppress NO production. In particular, the extracts obtained using 30% ethanol showed a strong tendency to suppress NO production, and among the extracts obtained using 30% ethanol, extract 2 was found to suppress NO production significantly more than extract 4.

[0082] Measurement of the anti-allergic effect of licorice extract The anti-allergic effects of the prepared licorice extracts 1-4 were measured. The relative amount of granulocytes released when IgE is cross-linked by an antigen was measured, and the anti-allergic effect was evaluated by its inhibitory effect. More specifically, the procedure was as follows. (Test method) Rat basophilic leukemia cells RBL-2H3 (hereinafter abbreviated as "RBL-2H3 cells") were seeded in 96-well plates and cultured overnight. Medium containing anti-DNP-IgE antibody was added, and after reacting at 37°C for 2 hours, the cells were washed with buffer solution. Licorice extracts were added to final concentrations of 500 μg / mL and 250 μg / mL, and after reacting at 37°C for 10 minutes, DNP (2,4-dinitrophenol)-labeled human serum albumin was added, and the cells were reacted at 37°C for 3 hours. Cells with only buffer solution added were used as an untreated control and were tested similarly. Cells with medium without anti-DNP-IgE antibody added, followed by sequential addition of buffer solution and DNP-labeled human serum albumin, were used as an unstimulated antigen control. After transferring the entire cell supernatant to empty wells, lysis buffer was added to the cells, and the cells were allowed to stand at room temperature for 10 minutes to obtain cell lysates. The cell supernatant and cell lysate were mixed with the substrate solution and reacted at 37°C for 25 minutes, after which the reaction was stopped by adding Glycine buffer. Additionally, a sample blank was prepared by adding Glycine buffer to the cell supernatant and cell lysate, reacting at 37°C for 25 minutes, and then adding the substrate solution. (Measurement method) Using a microplate reader, the absorbance of p-nitrophenol, produced by the reaction of β-hexosamidase (abundantly present in granules) with the substrate, was measured. (Measurement wavelength: 405 nm, reference wavelength: 650 nm) (Calculation method) The degranulation rate was calculated from the absorbance of each test solution relative to the absorbance of the untreated control using the following formula.

[0083] Release rate (%)= Absorbance of the cell supernatant ※ / ( Absorbance of the cell supernatant side) ※ + Absorbance on the cell lysate side ※ ) *: Value after subtracting the sample blank. Degranulation rate (%)= (Release rate of test solution - Release rate of unstimulated antigen control) / (Release rate in untreated control - Release rate in antigen-unstimulated control) × 100

[0084] Test results The degranulation rate (%) of each licorice extract is shown in the table below.

[0085] [Table 4]

[0086] All extracts were found to suppress degranulation. In particular, extract 2, obtained by extracting licorice from Hokkaido with 30% ethanol, showed a strong tendency to suppress degranulation, and was found to suppress degranulation significantly more effectively than extract 4.

Claims

1. A composition containing glycyrrhizic acid, liquiritin, and isoliquiritin, The mass ratio of glycyrrhizic acid to liquiritin (glycyrrhizic acid:liquiritin) is 1:0.3 to 2. The mass ratio of glycyrrhizic acid to isoliquiritin (glycyrrhizic acid:isoliquiritin) is 1:0.5 to 3. composition.

2. The mass ratio of glycyrrhizic acid to isoliquiritin (glycyrrhizic acid:isoliquiritin) is 1:1.4 to 3. The composition according to claim 1.

3. When the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, the total amount of glycyrrhizic acid, liquiritin, and isoliquiritin is 75 to 95 parts by mass. The composition according to claim 1 or 2.

4. When the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, the amount of glycyrrhizic acid is 1 to 50 parts by mass. The composition according to claim 1 or 2.

5. When the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, the amount of glycyrrhizic acid is 15 to 35 parts by mass. The composition according to claim 1 or 2.

6. When the total amount of glycyrrhizic acid, liquiritin, isoliquiritin, ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin is 100 parts by mass, isoliquiritin is present in 37 to 50 parts by mass. The composition according to claim 3.

7. The composition according to claim 1 or 2, further comprising ononine, liquiritigenin, isoliquiritigenin, formononetin, and glycicoumarin.

8. The composition according to claim 1 or 2, wherein the composition is water or aqueous ethanol extract of licorice.

9. The composition according to claim 1 or 2, which is an anti-inflammatory composition.

10. The composition according to claim 1 or 2, which is an anti-allergic composition.

11. A topical preparation comprising the composition described in claim 1 or 2.

12. The topical preparation according to claim 10, which is a cosmetic or a topical pharmaceutical.

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