JP7296675B1 - food composition - Google Patents

Abstract

[PROBLEMS] To provide a novel food composition capable of further improving the bioavailability and bioavailability of diosgenin as compared with conventional ones. A food composition containing a diosgenin clathrate obtained by clathrating diosgenin with cyclodextrin and piperine. [Selection drawing] Fig. 1

Description

TECHNICAL FIELD The present invention relates to a food composition with improved bioavailability of diosgenin.

Diosgenin has a structure similar to that of dehydroepiandrosterone (DHEA), which is an intermediate of sex hormones, and is a lead compound of various hormone agents. In recent years, diosgenin has been reported to have various functionalities such as nutritional tonic action and fat burning action. Yams contain diostin (glycoside), which is a spirostane-type saponin. When yam is eaten, it is converted into diosgenin, the aglycone (non-sugar moiety) of diostin, mainly by gastric acid, and its functionality is enhanced in vivo. can be demonstrated.

However, diosgenin is a poorly water-soluble component and is also a component that is hardly absorbed by the body, and its low bioavailability is regarded as a problem. Unless the absorption or bioavailability of diosgenin is improved, it cannot reach parts of the body and show efficacy.

For example, Japanese Patent No. 6095591 (Patent Document 1) discloses a method for producing a yam extract containing 5 to 20% by mass of diosgenin in solid content. In addition, in Japanese Patent Application Laid-Open No. 2019-199445 (Patent Document 2), a composition that enhances the efficiency of absorption of diosgenin into the body contains diosgenin-containing powder and powdered oil containing 50% by mass or more of medium-chain fatty acids. Compositions for oral ingestion have been proposed. Also, Masaki Ogawara, "Pharmaceutical studies aimed at improving the bioavailability and tissue transfer of diosgenin, a poorly water-soluble compound," Josai University Graduate School of Pharmaceutical Sciences, Doctoral Thesis, 2014; Otsu No. 63 diosgenin clathrate with cyclodextrin (referred to as a "complex" in Non-Patent Document 1) is biologically superior to diosgenin alone and a physical mixture of diosgenin and cyclodextrin. A significant increase in availability is stated.

Patent No. 6095591 JP 2019-199445 A

Masaki Ogawara, "Pharmaceutical study aimed at improving the bioavailability and tissue migration of diosgenin, a poorly water-soluble compound," Josai University Graduate School of Pharmaceutical Sciences Doctoral Thesis 2014; B No. 63

An object of the present invention is to provide a novel food composition capable of improving the bioavailability and bioavailability of diosgenin as compared with the conventional ones.

(1) A food composition containing a diosgenin clathrate in which diosgenin is clathrated with cyclodextrin and piperine.

(2) The food composition according to (1), wherein the cyclodextrin is γ-cyclodextrin.

(3) The food composition according to (1) or (2), which contains a black pepper extract containing 90% by mass or more of piperine.

(4) The food composition according to any one of (1) to (3), wherein the daily intake of diosgenin is 25 mg or less.

(5) The food composition according to any one of (1) to (4), which contains piperine in a weight ratio of 0.04 to 0.4 relative to diosgenin.

(6) The food composition according to any one of (1) to (5), which has a bioavailability 3 to 10 times higher than that of the free diosgenin not clathrated with cyclodextrin.

(7) The food composition according to (6), which has higher bioavailability than the diosgenin educt that is not clathrated with cyclodextrin.

(8) The food composition according to any one of (1) to (7), further comprising vitamin C.

(9) The food composition according to (8), wherein the vitamin C is coated with palm oil.

(10) The food composition according to (8) or (9), which contains vitamin C in a weight ratio of 2 to 100 with respect to diosgenin.

According to the present invention, there is provided a food composition having a bioavailability 3 to 10 times higher than that of diosgenin free form, and a higher bioavailability than diosgenin free form and diosgenin clathrate. can do.

4 is a graph showing the results of Experimental Example 1. FIG. 10 is a graph showing the results of RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) of the cognitive function test in Experimental Example 2. FIG. 10 is a graph showing the results of an anti-fatigue VAS (Visual Analogue Scale) of the Japan Fatigue Society in Experimental Example 2. FIG. 10 is a graph showing results in the brain of Experimental Example 3. FIG. 10 is a graph showing the results in blood of Experimental Example 3. FIG. 7 is a graph showing the results of Experimental Example 4. FIG. 10 is a graph showing the results of RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) of the cognitive function test in Experimental Example 5. FIG. 10 is a graph showing the results of an anti-fatigue VAS (Visual Analogue Scale) of the Japan Fatigue Society in Experimental Example 5. FIG.

The present invention provides a food composition containing a diosgenin clathrate in which diosgenin is clathrated with cyclodextrin and piperine. Here, "food composition" refers to an edible composition that is routinely ingested as food by humans.

The diosgenin inclusion compound in the food composition of the present invention encloses diosgenin (guest) in the hydrophobic cavity of cyclodextrin (host). As diosgenin, commercially available ones can be used without any particular limitation. ) and the like are suitable examples.

The cyclodextrin in the food composition of the present invention includes α-cyclodextrin (n=6), β-cyclodextrin (n=7), γ-cyclodextrin, depending on the number (n) of D-glucopyranose that constitutes it. (n=8). Among these, γ-cyclodextrin or β-cyclodextrin is preferable, but β-cyclodextrin is currently not restricted in Japan, but in the United States and Europe, the World Food Additives Expert Meeting (JECFA: FAO/WHO Joint Expert) Committee on Food Additives) limits the ADI (Acceptable Daily Intake) to 5 mg/kg/day (up to 300 mg per day for a person weighing 60 kg). γ-Cyclodextrin is particularly preferred because it does not have an ADI (it has been determined by JECFA that there is no need to set an ADI).

Commercially available cyclodextrins can also be used without particular limitation, and suitable examples thereof include CAVAMAX (registered trademark) W8 Food (manufactured by Wacker Chemie) as γ-cyclodextrin.

The diosgenin inclusion complex is described, for example, in Non-Patent Document 1, Ameer Ghuzlaan et al., "Prednisone/Cyclodextrin Inclusion Complexation: Phase Solubility, Thermodynamic, Physicochemical and Computational Analysis", Journal of Solution Chemistry volume 38, pages 83- 94 (2009), adding diosgenin and cyclodextrin mixed in a desired molar ratio to water by a coprecipitation method, stirring in distilled water, filtering the resulting suspension, and drying and pulverizing the residue. can be created with

In the diosgenin clathrate in the food composition of the present invention, the molar ratio of cyclodextrin to diosgenin is preferably in the range of 0.8 to 2.0 per 1 diosgenin when γ-cyclodextrin is used. , 1.0 to 1.3. This is because when the molar ratio of diosgenin:γ-cyclodextrin is less than 1:0.8, γ-cyclodextrin cannot fully clathrate diosgenin and tends to remain as a diosgenin free form with poor absorption rate. In addition, when the diosgenin:γ-cyclodextrin ratio exceeds 1:2.0, γ-cyclodextrin completely clathrates diosgenin and cannot react. This is because there is a tendency for the absorbability to be affected (inhibition of absorption of highly effective lipid components, etc.).

In addition, in the food composition of the present invention, a commercially available diosgenin clathrate may of course be used, and a preferred example is diosgenin CD (manufactured by Anti-Aging Pro Co., Ltd.).

The intake amount of the food composition of the present invention is appropriately determined according to the subject's sex, weight, health condition, etc., but the daily intake of diosgenin is preferably 25 mg or less. When the daily intake of diosgenin exceeds 25 mg, the inclusion process increases the absorption rate by about 5 times, resulting in an intake of 125 mg in terms of free form of diosgenin. This is because there is a tendency for the possibility of an imbalance of sex hormones such as (dehydroepiandrosterone) to occur. In addition, the daily intake of diosgenin should be 5 mg or more and less than 10 mg because 25 mg or more and 50 mg in terms of diosgenin educt intake is the same as the recommended intake amount for which the safety of DHEA has been confirmed. is more preferred. The above amount of the food composition may be ingested at once or divided into several times a day.

Commercially available piperine can be used without particular limitation in the food composition of the present invention. For reasons of removal, it is preferred to include a black pepper extract containing 90% by weight or more of piperine. Suitable examples of such a black pepper extract include Bioperine (manufactured by Sabinsa Japan Corporation, 95% or more of piperine).

Here, FIG. 1 is a graph showing the results of Experimental Example 1, which will be described later. The diosgenin clathrate, the diosgenin not clathrated with cyclodextrin (diosgenin free form), and piperine (1 mg, 5 mg), respectively. ) in the blood diosgenin concentration over time (0, 3, 6 and 12 hours after ingestion). When the diosgenin clathrate is combined with piperine, as in the food composition of the present invention, the blood diosgenin concentration is markedly higher than that of the diosgenin free form alone or the combination of the diosgenin free form and piperine. Moreover, the diosgenin concentration in the blood was higher than that of the diosgenin clathrate alone. Thus, according to the food composition of the present invention, the bioavailability is 3 to 10 times (preferably 6 to 10 times) that of diosgenin free form, and diosgenin free form and diosgenin clathrate Food compositions can be provided that have greater bioavailability.

The food composition of the present invention preferably contains piperine in a weight ratio of 0.04 to 0.4 to diosgenin. This is because if the weight ratio of diosgenin:piperine is less than 1:0.04, piperine tends to be less effective in promoting absorption. This is because, if it exceeds, the problem of piperine irritation tends to occur although the absorption-enhancing effect of piperine does not change. In addition, it is preferable to contain piperine at a weight ratio of 0.1 to 0.24 with respect to diosgenin, because the problem of irritation is less likely to occur while the absorption-promoting effect of piperine is sufficiently obtained. A preferred example is a case where 0.5 to 1.2 mg of piperine is contained in 5 to 10 mg of diosgenin.

The food composition of the present invention preferably further contains vitamin C. Further inclusion of vitamin C further enhances bioavailability. Vitamin C may be either uncoated or coated, but coated vitamin C is preferred because it enhances bioavailability. Coating materials include palm oil, hydrogenated rapeseed oil, and corn protein, but corn protein dissolved in a high-temperature solution can be sprayed to reduce vitamin C. Palm oil with a melting point of about 37° C. is particularly preferred because hydrogenated rapeseed oil with a low melting point may melt in the stomach and be affected by gastric acid.

Commercially available vitamin C can be used without particular limitation, and preferred examples include ascorbic acid (L-ascorbic acid) (fine granules) (manufactured by DSM), vitamin C (L-ascorbic acid P) (manufactured by Eiken Shoji Co., Ltd.), ascorbic acid (manufactured by Nakahara Co., Ltd.), and the like.

Here, FIGS. 2 and 3 are graphs showing the results of Experimental Example 2 to be described later, diosgenin free form only (placebo), diosgenin clathrate only, diosgenin clathrate + vitamin C, diosgenin clathrate + Intake of coated vitamin C was performed for 16 weeks, and at the start of intake (0 w) and after 16 weeks of intake (16 w), cognitive function test RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) ( RBANS-Total) (Fig. 2) and the anti-fatigue VAS (Visual Analogue Scale) of the Japan Fatigue Society (Fig. 3). It can be seen that the combination of diosgenin clathrate+vitamin C with coating showed the highest values for both evaluation items.

4 and 5 are graphs showing the results of Experimental Example 3, which will be described later. Diosgenin clathrate alone, diosgenin clathrate + piperine, and diosgenin clathrate + piperine + coated vitamin C were ingested. , shows the results of measuring diosgenin concentrations in blood and brain. In particular, it can be seen that simultaneous ingestion of diosgenin clathrate + piperine + coated vitamin C showed high values in the brain.

Furthermore, FIG. 6 is a graph showing the results of Experimental Example 4, which will be described later. Diosgenin clathrate only, diosgenin clathrate + piperine + vitamin C with coating (in the case of palm oil coating, in the case of hardened rapeseed oil coating) ) and measured the blood diosgenin concentration. It can be seen that the simultaneous intake of diosgenin clathrate + piperine + vitamin C with coating (palm oil coating) (coating VC-2 in Fig. 6) showed high values.

The food composition of the present invention preferably contains vitamin C in a weight ratio of 2-100 to diosgenin. This is because when the weight ratio of diosgenin:vitamin C is less than 1:2, the effect of vitamin C tends to be less likely to be exhibited. This is because vitamin C tends to be excreted without being fully absorbed. In addition, it is preferable that vitamin C is contained in a weight ratio of 10 to 24 with respect to diosgenin for the reason that it is the optimum vitamin C intake taking into consideration the optimum intake of diosgenin. A preferred example is a case where 50-240 mg of vitamin C is contained in 5-10 mg of diosgenin.

The food composition of the present invention may contain a food-acceptable carrier and other known additives in addition to the above components. Examples of the above additives include excipients, binders, lubricants, disintegrants, coloring agents, flavoring agents, emulsifiers, surfactants, solubilizers, and suspending agents that are commonly used in foods and pharmaceuticals. , tonicity agents, buffers, preservatives, antioxidants, stabilizers, absorption enhancers, and the like, and if desired, these can be used in appropriate combination.

The food composition of the present invention may be used to produce foods that are eaten on a daily basis, and to produce functional foods such as health foods, functional foods, foods for specified health uses, supplements, and supplements. may be used for The shape of the food is also not particularly limited, and solid, liquid, powder, gel and the like can be exemplified.

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

<Experimental example 1>
The following two types of diosgenin ・ Diosgenin free form (Geopower 15, manufactured by Anti-Aging Pro Co., Ltd.) 8 mg
・ Diosgenin clathrate (Diosgenin CD, manufactured by Anti-Aging Pro Co., Ltd.) 45 mg (Diosgenin content: 8 mg, γ-cyclodextrin is used for the clathrate)
was dissolved in 790 μL (672 g) of water, and forced orally ingested to an 8-week-old mouse (dddY female, obtained from Japan SLC, Inc.). Further, for each of the same diosgenin free form and diosgenin clathrate, 1 mg or 5 mg of black pepper extract (Bioperin (manufactured by Sabinsa Japan Corporation, piperine 95% or more)) was further added, and added to 790 μL (672 g) of water. It was dissolved and similarly gavaged to another 8-week-old mouse.

200 μL of blood was collected from each mouse 3, 6, 12 hours after ingestion. Blood was centrifuged (10000×g, 4° C., 10 min centrifugation) and plasma aliquots were removed and extracted with methanol. For each obtained extract, diosgenin in the prepared sample was quantified using a liquid chromatography mass spectrometer (LCMS-9050, manufactured by Shimadzu Corporation). Table 1 shows the results.

A graph of Table 1 is shown in FIG. In FIG. 1, the vertical axis indicates the blood diosgenin concentration (μg/mL), and the horizontal axis indicates the elapsed time (unit: hour) after ingestion. When the diosgenin clathrate is combined with piperine, as in the food composition of the present invention, the blood diosgenin concentration is markedly higher than that of the diosgenin free form alone or the combination of the diosgenin free form and piperine. Moreover, the diosgenin concentration in the blood was higher than that of the diosgenin clathrate alone. Thus, according to the food composition of the present invention, the bioavailability is 3 to 10 times (preferably 6 to 10 times) that of diosgenin free form, and diosgenin free form and diosgenin clathrate Food compositions can be provided that have greater bioavailability.

<Experimental example 2>
Hard capsule containing 8 mg of diosgenin free form or 45 mg of diosgenin clathrate (diosgenin content: 8 mg) same as used in Experimental Example 1 (capsule: Coni-Snap (registered trademark) hard gelatin capsule, manufactured by Lonza Co., Ltd.) 1 The grains continued to be taken at lunch for 16 weeks. In addition, 45 mg of the same diosgenin clathrate (diosgenin content: 8 mg) was added with 100 mg of vitamin C (without coating, with coating (palm oil coating (Vitacoat C-95, manufactured by Yokohama Yushi Kogyo Co., Ltd.)), labeled as "coating VC". )) (capsule: Coni-Snap (registered trademark) hard gelatin capsule, manufactured by Lonza Co., Ltd.) was taken at every lunch for 16 weeks. Subjects were 3 healthy subjects in each group aged 55 or over and under 65 who were concerned about forgetfulness.

At the start of intake (0w) and after 16 weeks of intake (16w), cognitive function test RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) (RBANS-Total) and anti-fatigue VAS of the Japan Fatigue Society (Visual Analogue Scale) and were evaluated respectively. Table 2 shows the results of RBANS-Total, and Table 3 shows the results of anti-fatigue VAS.

Further, a graph of Table 2 is shown in FIG. 2, and a graph of Table 3 is shown in FIG. In FIG. 2, the vertical axis is the RBANS-Total score, and in FIG. 3, the horizontal axis is the anti-fatigue VAS score. In FIGS. 2 and 3, when diosgenin free form is used, "placebo" is used, when uncoated vitamin C is used, "diosgenin clathrate + vitamin C" is used, and when coated vitamin C is used, " Diosgenin clathrate + coating VC". It can be seen that the combination of diosgenin clathrate + coating VC showed the highest values for both evaluation items.

<Experimental example 3>
When only 45 mg of the same diosgenin clathrate used in Experimental Example 1 (8 mg of diosgenin content) was used, and when 1 mg of the same black pepper extract as used in Experimental Example 1 was added, When 1 mg of the same black pepper extract and 100 mg of the same coated vitamin C as used in Experimental Example 2 were added, each was dissolved in 790 μL (672 g) of water, and an 8-week-old mouse (dddY female , obtained from Japan SLC Co., Ltd.).

As in Example 1, 200 μL of blood was collected from each mouse at 3, 6, and 12 hours after ingestion. Blood was centrifuged and plasma aliquots were removed and extracted with methanol. The cerebral cortex was collected, homogenized, and extracted with methanol in the same manner. For each extract, the same liquid chromatography-mass spectrometer used in Example 1 was used to quantify diosgenin in the prepared samples. The results in brain are shown in Table 4, and the results in blood are shown in Table 5.

Further, a graph of Table 4 is shown in FIG. 4, and a graph of Table 5 is shown in FIG. In FIG. 4, the vertical axis indicates the cortical diosgenin concentration (μg/g), and the horizontal axis indicates the elapsed time (unit: hour) after ingestion. In FIG. 5, the vertical axis indicates the blood diosgenin concentration (μg/mL), and the horizontal axis indicates the elapsed time (unit: hours) after ingestion. In particular, it can be seen that simultaneous ingestion of diosgenin clathrate + piperine + coated VC showed a high value in the brain.

<Experimental example 4>
In the case of only 45 mg of the same diosgenin clathrate used in Experimental Example 1 (diosgenin content: 8 mg), 1 mg of the same black pepper extract as used in Experimental Example 1 and vitamin C with any of the following coatings:
・ Rapeseed hardened oil coating (VC-90R, manufactured by NOF Corporation) (referred to as “coating VC-1”)
・ Palm oil coating (Vitacoat C-95, manufactured by Yokohama Oil Industry Co., Ltd.) (referred to as “coating VC-2”)
100 mg was dissolved in 790 μL (672 g) of water, and 8-week-old mice (dddY female, obtained from Japan SLC, Inc.) were forcibly ingested.

As in Example 1, 200 μL of blood was collected from each mouse at 3, 6, and 12 hours after ingestion. Blood was centrifuged to remove plasma aliquots and extracted with methanol. Diosgenin in the prepared samples was quantified using the same liquid chromatography-mass spectrometer as used in Experimental Example 1. Table 6 shows the results.

A graph of Table 6 is shown in FIG. In FIG. 6, the vertical axis indicates the blood diosgenin concentration (μg/mL), and the horizontal axis indicates the elapsed time (unit: hour) after ingestion. It can be seen that simultaneous intake of diosgenin clathrate + piperine + vitamin C with coating (palm oil coating) (coating VC-2) showed high values.

<Experimental example 5>
To 8 mg of the free diosgenin or 45 mg of the diosgenin clathrate (diosgenin content: 8 mg) used in Experimental Example 1, 30 mg, 100 mg or 500 mg of vitamin C (palm oil coating (Vitacoat C-95, Yokohama Yushi Kogyo Co., Ltd.) (manufactured by the same company) and labeled as “coating VC”), one hard capsule (capsule: Coni-Snap (registered trademark) hard gelatin capsule, manufactured by Lonza Co., Ltd.) was ingested at each lunch for 16 weeks. Subjects were 3 healthy subjects in each group aged 55 or over and under 65 who were concerned about forgetfulness.

At the start of intake (0w) and after 16 weeks of intake (16w), cognitive function test RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) (RBANS-Total) and anti-fatigue VAS of the Japan Fatigue Society (Visual Analogue Scale) and were evaluated respectively. Table 7 shows the results of RBANS-Total, and Table 8 shows the results of anti-fatigue VAS.

Further, a graph of Table 7 is shown in FIG. 7, and a graph of Table 8 is shown in FIG. In FIG. 7, the vertical axis is the RBANS-Total score, and in FIG. 8, the horizontal axis is the anti-fatigue VAS score. In Figures 7 and 8, the case of using diosgenin free form is indicated as "placebo", and the case of using coated vitamin C is indicated as "diosgenin clathrate + coated VC" (30 mg, 100 mg, 500 mg). . It can be seen that the combination of diosgenin clathrate + coating VC showed the highest values for both evaluation items.

It should be considered that the embodiments disclosed this time are illustrative in all respects and not restrictive. The scope of the present invention is indicated by the scope of the claims rather than the above description, and is intended to include all modifications within the scope and meaning of equivalents of the scope of the claims.

Claims (8)

A food composition containing a diosgenin clathrate in which diosgenin is clathrated with cyclodextrin, piperine, and vitamin C coated with palm oil . A food composition according to claim 1, wherein the cyclodextrin is γ-cyclodextrin. 2. The food composition according to claim 1, comprising a black pepper extract containing 90% by mass or more of piperine. 2. The food composition according to claim 1, wherein the daily intake of diosgenin is 25 mg or less. The food composition according to claim 1, comprising piperine in a weight ratio of 0.04 to 0.4 to diosgenin. 2. The food composition according to claim 1, which has a bioavailability 3 to 10 times higher than that of free diosgenin not clathrated with cyclodextrin. 7. A food composition according to claim 6, which has a higher bioavailability than diosgenin educt without inclusion with cyclodextrin. The food composition according to claim 1 , comprising vitamin C in a weight ratio of 2-100 to diosgenin.

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