JP2012017322A - Method of producing hesperidin composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hesperidin composition that has high hesperidin content and is excellent in solubility, and to provide a method of producing the hesperidin composition.SOLUTION: The method of producing the hesperidin composition includes a step of heating hesperidin and a hesperidin sugar adduct at 100-180°C in the presence of an aqueous medium.

Description

  The present invention relates to a method for producing a hesperidin composition.

Hesperidin, a kind of flavonoid, is also called vitamin P and is a substance known to be contained in a large amount in citrus peels. Hesperidin has various physiological actions such as strengthening of capillaries, prevention of bleeding, and adjustment of blood pressure, and is widely used in foods, pharmaceuticals and the like. However, hesperidin dissolves in an alkaline aqueous solution, but hardly dissolves in a neutral to acidic aqueous solution. For example, the solubility in water at 25 ° C. is only 0.02 mg / g.
Then, the technique which improves this is examined, for example, the alpha-glucosyl hesperidin which made glucose couple | bond with hesperidin is proposed (patent document 1). α-Glucosyl hesperidin has an advantage that the solubility in water at 25 ° C. is as high as 200 mg / g or more and the same function as hesperidin is exhibited.

  On the other hand, studies for solubilizing hesperidin have also been conducted. For example, a method in which hesperidin glycoside is added to citrus juice and fruit juice and heated to dissolve flavonoid compounds such as hesperidin (Patent Document 2); poorly water-soluble flavoids such as hesperidin and β-cyclodextrin A heat-treated flavonoid is included in β-cyclodextrin after heat treatment, and α-glucosyl hesperidin is allowed to coexist (Patent Document 3); flavonoids such as hesperidin and soybean saponin and / or malonyl A method of solubilizing flavonoids by coexisting isoflavone glycosides and heat treatment (Patent Document 4) has been proposed. In these methods, the heat treatment of hesperidin is performed at around 70 ° C to 90 ° C.

Japanese Patent No. 3549436 JP 2000-236856 A JP 2008-271839 A International Publication No. 2005/003112

Although hesperidin glycosides such as α-glucosyl hesperidin have high solubility in water, the cost is high because the production process is complicated. For this reason, it is economically not preferable to use hesperidin glycoside instead of hesperidin. On the other hand, although a method for increasing the solubility of hesperidin using the above-mentioned specific glycoside is known, only a hesperidin composition having a low hesperidin content is obtained, and a method capable of sufficiently dissolving hesperidin Was not known.
Accordingly, an object of the present invention is to provide a hesperidin composition having a high hesperidin content and excellent solubility, and a method for producing the hesperidin composition.

  As a result of various studies on the solubilization technology of hesperidin, the present inventors have found that the concentration of hesperidin can be dramatically increased by heat-treating hesperidin and hesperidin sugar adduct at 100 ° C. or higher in the presence of an aqueous medium. Furthermore, it has been found that in the composition subjected to such treatment, precipitation of hesperidin is suppressed even at room temperature and high solubility of hesperidin is maintained.

  That is, this invention provides the manufacturing method of a hesperidin composition including the process of heat-processing hesperidin and a hesperidin sugar adduct at 100-180 degreeC in presence of an aqueous medium.

The use of α-glucosyl hesperidin as a solubilizing agent for hesperidin is conventionally known. However, as described in Patent Document 3, the solubilizing action by α-glucosyl hesperidin is limited. It was. Therefore, it can be said that the above-mentioned effect due to the heat treatment at 100 ° C. or higher is an unexpected effect that cannot be predicted from the prior art.
The reason why the above problem can be solved by heat-treating hesperidin and hesperidin sugar adduct at 100 ° C. or higher is not clear, but is estimated as follows from UV spectrum analysis. Although hesperidin and hesperidin sugar adducts differ in solubility, each molecule is considered to be dissolved in water by self-association of each other, laminating the hydrophobic part, and taking the structure with the hydrophilic part outward . Here, when both components coexist in an aqueous medium and heat of 100 ° C. or higher is applied, the layered structure collapses and falls apart, and an interaction occurs between hesperidin and hesperidin sugar adduct, resulting in hesperidin and hesperidin. It is thought that the solubility of hesperidin is drastically improved by creating a new laminated structure in which sugar adducts are mixed and maintaining this laminated structure even after cooling.

  According to the present invention, it is possible to increase the concentration of hesperidin dissolved in water or the like, and it is possible to provide a hesperidin composition having excellent solubility despite a high hesperidin content.

  In the production method of the present invention, a step of heat-treating hesperidin and hesperidin sugar adduct at 100 to 180 ° C. in the presence of an aqueous medium is performed.

Hesperidin is a compound in which rutinose (L-rhamnosyl- (α1 → 6) -D-glucose) is β-bonded to the hydroxyl group at position 7 of hesperetin (5,7,3′-trihydroxy-4′-methoxyflavanone). .

  Hesperidin sugar adduct is a compound in which 1 to 10 sugars are further bound to hesperidin. Examples of the sugar include glucose, maltose, fructose, rhamnose, lactose and the like. Among these, from the viewpoint of solubility and solubilizing power, glucosyl hesperidin in which 1 to 10 glucoses are bonded to hesperidin is preferable, and monoglucosyl hesperidin in which 1 glucose is further bonded is preferable. Moreover, the addition number of glucose may have distribution, and the average addition mole number of glucose with respect to 1 mol of hesperidins is 1-10. As described above, hesperidin itself is a glycoside in which hesperetin is used as an aglycone and a sugar is bound thereto. In the present invention, in order to distinguish from this, a substance in which a sugar is further bonded to hesperidin is referred to as a hesperidin sugar adduct.

  These hesperidins and hesperidin sugar adducts can be industrially produced by a known method using chemical synthesis or enzymatic reaction. Hesperidin can also be obtained by extraction from natural products containing it, preferably from plants. These substances are also manufactured and sold as reagents and the like. As an example of commercially available hesperidin, hesperidin “Hamari” manufactured by Hamari Pharmaceutical Co., Ltd. may be mentioned. Examples of commercially available hesperidin sugar adducts include “Hayashibara Hesperidin S” from Hayashibara Bioscience Institute.

The aqueous medium used in the present invention refers to water and an aqueous solution of an organic solvent. Examples of water include tap water, distilled water, ion exchange water, and purified water. The organic solvent is not particularly limited as long as it is uniformly mixed with water. As the organic solvent, alcohol having 4 or less carbon atoms is preferable, methanol and ethanol are more preferable, and ethanol is more preferable from the viewpoint of being applicable to foods.
It is preferable to use an aqueous solution of an organic solvent as the aqueous medium because the content of hesperidin in the resulting hesperidin composition can be increased. The concentration of the organic solvent in the aqueous solution is preferably 0.1 to 80% by mass, more preferably 1 to 70% by mass, and still more preferably 5 to 60% by mass.
The aqueous medium used in the present invention may contain a solute. The solute is not particularly limited, and examples thereof include acids such as amino acids, inorganic salts, organic salts, and sugars. Soy sauce, ponzu, sauce, fruit juice, vegetable juice, coffee, tea, etc. may be used.

Since hesperidin has low solubility in water, it is preferably dispersed in an aqueous medium and present in the form of a slurry. The content of hesperidin in the aqueous medium is preferably 0.1 to 100 g / L, more preferably 0.5 to 50 g / L, and still more preferably 1 to 20 g / L from the viewpoint of fluidity.
The hesperidin sugar adduct is preferably dissolved in an aqueous medium. The content of the hesperidin sugar adduct in the aqueous medium is preferably from 0.1 to 200 g / L, more preferably from 0.5 to 100 g / L, still more preferably from 1 to 50 g / L, from the viewpoint of fluidity.

  In the aqueous medium, the mass ratio of hesperidin to the hesperidin sugar adduct is preferably from 0.1 to 20, more preferably from 0.2 to 10, and even more preferably from the viewpoint of the solubility of the hesperidin composition obtained after heat treatment and cooling. 3-5 are preferable.

The method for heat-treating hesperidin and hesperidin sugar adduct in the presence of an aqueous medium is not particularly limited, and a known method can be applied.
The temperature of the heat treatment is preferably from 100 to 180 ° C, more preferably from 110 to 170 ° C, further preferably from 120 to 160 ° C, and further preferably from 120 to 150 ° C, from the viewpoint of improving the solubility of hesperidin and thermal stability. Examples of the heating means include water vapor and electricity.

  The pressure during the heat treatment is preferably 0 to 10 MPa, more preferably 0.1 to 8 MPa, further preferably 0.1 to 6 MPa, further preferably 0.2 to 6 MPa, and further preferably 0.2 to 4 MPa in terms of gauge pressure. Preferably, 0.25 to 2 MPa is more preferable, 0.3 to 1.5 MPa is further preferable, and 0.3 to 0.6 MPa is further preferable. Moreover, it is preferable to set it more than the saturated vapor pressure of water. Gas may be used for pressurization, and examples of the gas used include inert gas, water vapor, nitrogen gas, helium gas, and the like. The pressurization may be adjusted by a back pressure valve without using gas.

  The heat treatment can be performed by any method such as a batch method, a semi-batch method, or a flow reaction method. Among these, the flow-type reaction method is preferable in that the reaction time can be easily controlled.

The heat treatment time is preferably from 0.1 to 30 minutes after the aqueous medium reaches the set temperature, more preferably from 0.2 to 15 minutes, and further from 0.5 to 0.5, from the viewpoint of improving the solubility and heat stability of hesperidin. 8 minutes is preferred.
In the case of the flow reaction method, the heat treatment time is an average residence time calculated by dividing the volume of the high-temperature and high-pressure part of the reactor by the supply rate of the aqueous medium.

  The flow rate of the aqueous medium in the case of the flow reaction method varies depending on the volume of the reactor. For example, when the reactor volume is 100 mL, 3.3 to 200 mL / min is preferable, and further 6.7 to 150 mL / min. Is preferred.

After the heat treatment, it is preferable to perform a step of cooling the reaction solution obtained by the heat treatment to 90 ° C. or lower, preferably 50 ° C. or lower, more preferably 30 ° C. or lower. The lower limit of cooling is not required to be frozen, but is preferably 0 ° C or higher, and more preferably 10 ° C or higher. During cooling, the reaction solution may be mixed and stirred for 0.5 to 5 days, preferably 1 to 3 days.
The cooling rate of the reaction solution calculated from the time required to decrease from the heat treatment temperature to 90 ° C is 0.1 ° C / s or more, further 0.2 ° C / s or more, further 0.5 ° C / s or more, It is preferably 1 ° C./s or more, more preferably 3 ° C./s or more, and further preferably 5 ° C./s or more. The greater the cooling rate, the better the solubility. For this reason, the upper limit of the cooling rate is not particularly defined, but is preferably 100 ° C./s or less, and more preferably 50 ° C./s or less.

  Furthermore, it is preferable to perform the step of removing the solid part from the reaction solution from the viewpoint of increasing the solubility of the resulting hesperidin composition. The method for removing the solid part is not particularly limited, and can be performed, for example, by centrifugation or decantation.

The hesperidin composition thus obtained is excellent in solubility because the deposition of hesperidin is suppressed even at room temperature despite the high hesperidin content.
The amount of hesperidin dissolved in the hesperidin composition is preferably 1.3 g / L or more, more preferably 2 g / L or more, still more preferably 3 g / L or more, and still more preferably 5 g / L or more. The amount dissolved in this specification is the amount dissolved in water at 25 ° C.
The hesperidin composition of the present invention may be in the form of an aqueous solution, or the amount of water can be adjusted to form a paste. Moreover, it can also be made into the form of solid substances, such as a powder form, a granular form, and a solid form, by removing a water | moisture content. Examples of means for removing moisture include freeze drying, evaporation to dryness, and spray drying.

  The mass ratio of hesperidin to hesperidin sugar adduct in the hesperidin composition of the present invention is 0.3 to 10, more preferably 0.4 to 8, still more preferably 0.5 to 8, and still more preferably 1 to 5. It is.

<Quantification of hesperidin and hesperidin sugar adduct>
Hesperidin and hesperidin sugar adducts are quantified using a high-performance liquid chromatograph manufactured by Hitachi, equipped with an intact column Cadenza CD-C18 (4.6 mmφ × 150 mm, 3 μm) and a gradient method at a column temperature of 40 ° C. It was. The mobile phase A solution was 0.05 mol / L acetic acid aqueous solution, the B solution was acetonitrile, and the solution was fed at 1.0 mL / min. The gradient conditions are as follows.
Time (min) A liquid (%) B liquid (%)
0 85 15
20 80 20
35 10 90
50 10 90
40.1 85 15
60 85 15
The sample injection amount was 10 μL, and detection was quantified by absorbance at a wavelength of 283 nm.

Example 1
Hesperidin preparation (Hesperidin “Hamari” (trade name), manufactured by Hamari Pharmaceutical Co., Ltd., hesperidin content 90 mass%, the same applies hereinafter) and monoglucosyl hesperidin preparation (Hayashibara Hesperidin S (trade name), Hayashibara Biological Co., Ltd.) Chemical Research Laboratory, hesperidin content 17% by mass, monoglucosyl hesperidin content 74% by mass, the same applies hereinafter) dispersed in distilled water at 10.0 g / L and dissolved at 4.3 g / L in the slurry supply tank And stirred uniformly. The liquid in the slurry supply tank was supplied at 100 mL / min to a stainless-steel flow reactor (made by Nitto Koatsu Co., Ltd.) having an internal volume of 100 mL, and the reaction was carried out at 120 ° C. (average residence time 1 minute). The pressure was adjusted to 1.5 MPa with an outlet valve. The reaction liquid was extracted from the outlet of the reactor, cooled to room temperature (25 ° C.), and recovered in a reaction liquid recovery tank. Cooling was performed by continuously exchanging heat with the cooling water of the reaction liquid extracted from the outlet of the flow reactor using a double tube cooler.
The collected reaction solution was stirred at room temperature for 3 days, and then the solid part was filtered off to obtain a hesperidin composition as a hesperidin-containing aqueous solution. The reaction conditions and the results of measuring the concentration of hesperidin (HES) and monoglucosyl hesperidin (mGHES) in the composition are shown in Table 1 (hereinafter the same).

Example 2
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that the reaction temperature was 150 ° C. Furthermore, water was removed by freeze-drying to obtain a powdered hesperidin composition. When the powdered hesperidin composition was redissolved in water (25 ° C.), it was confirmed that it was dissolved even at 10 g / L.

Example 3
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that the reaction temperature was 180 ° C.

Example 4
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 2 except that the concentration of the monoglucosyl hesperidin preparation in distilled water was 1.1 g / L.

Example 5
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 2 except that the concentration of the hesperidin preparation in distilled water was 20 g / L.

Comparative Example 1
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that the reaction temperature was 25 ° C.

Comparative Example 2
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that the reaction temperature was 90 ° C.

Example 6
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that the concentration of the monoglucosyl hesperidin preparation in distilled water was 10 g / L.

Example 7
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 6 except that the reaction temperature was 150 ° C.

Example 8
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 6 except that the reaction temperature was 180 ° C.

Comparative Example 3
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 6 except that the reaction temperature was 90 ° C.

  Table 1 shows the mass ratio of HES to mGHES of the hesperidin compositions obtained in Examples 1 to 8 and Comparative Examples 1 to 3.

  As is apparent from Table 1, by heat-treating hesperidin and hesperidin sugar adduct at 100 to 180 ° C., a hesperidin composition having a high hesperidin content can be obtained, and the solubility of hesperidin is remarkably increased. I was able to.

Example 9
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 2, except that the hesperidin preparation was dispersed and the aqueous medium for dissolving the monoglucosyl hesperidin preparation was changed from distilled water to a 50 vol% ethanol aqueous solution. The results of measuring HES and mGHES in the composition are shown in Table 2 (hereinafter the same).

Comparative Example 4
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 9 except that the reaction temperature was 25 ° C.

  Table 2 shows the mass ratio of HES to mGHES in the hesperidin compositions obtained in Example 9 and Comparative Example 4.

  As is apparent from Table 2, a hesperidin composition having a high hesperidin content could be obtained by using an aqueous solution containing an organic solvent as the aqueous medium for the reaction.

Example 10
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that soy sauce (Yamasa soy sauce, pH 4.9, manufactured by Yamasa Soy Sauce Co., Ltd.) was used instead of distilled water. The results of measuring HES and mGHES in the composition are shown in Table 3 (hereinafter the same).

Example 11
Hesperidin composition as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that reduced salt soy sauce (Yamasa reduced salt soy sauce, pH 4.7, manufactured by Yamasa Soy Sauce Co., Ltd.) was used instead of distilled water, and the pressure was 0.3 MPa. I got a thing.

Example 12
A hesperidin composition was prepared as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that seasoned ponzu (Taste Pon, pH 2.0, manufactured by Mitsukan Group Inc.) was used instead of distilled water, and the pressure was 0.3 MPa. Obtained.

  As is apparent from Table 3, a hesperidin composition having a high hesperidin content could be obtained even using an aqueous medium containing an amino acid, a salt, or the like.

Example 13
A hesperidin composition was obtained as a hesperidin-containing aqueous solution in the same manner as in Example 1 except that the pressure was 0.3 MPa. The cooling rate obtained from the cooling time from 120 ° C. to 90 ° C. was 7.06 ° C./s.

Example 14
The hesperidin composition was prepared as a hesperidin-containing aqueous solution in the same manner as in Example 13 except that the cooling water temperature and flow rate were changed and the cooling rate obtained from the cooling time from 120 ° C. to 90 ° C. was 0.52 ° C./s. Obtained.

Claims (11)

  The manufacturing method of a hesperidin composition including the process of heat-processing hesperidin and a hesperidin sugar adduct at 100-180 degreeC in presence of an aqueous medium.   The method for producing a hesperidin composition according to claim 1, wherein the hesperidin sugar adduct is glucosyl hesperidin.   The method for producing a hesperidin composition according to claim 1, wherein the hesperidin sugar adduct is monoglucosyl hesperidin.   The method for producing a hesperidin composition according to any one of claims 1 to 3, wherein a mass ratio of hesperidin to hesperidin sugar adduct is 0.1 to 20 in the heat treatment step.   The method for producing a hesperidin composition according to any one of claims 1 to 4, wherein the aqueous medium is water or an aqueous solution containing an alcohol having 4 or less carbon atoms.   Furthermore, the manufacturing method of the hesperidin composition of any one of Claims 1-5 including the process of cooling the reaction liquid obtained by heat processing, and the process of removing a solid part from the cooled reaction liquid. .   The method for producing a speridine composition according to claim 6, wherein in the step of cooling the reaction solution, the cooling rate from the heat treatment temperature to 90 ° C is 0.1 ° C / s or more.   The method for producing a speridine composition according to any one of claims 1 to 7, wherein the form of the hesperidin composition is an aqueous solution or a powder.   A hesperidin composition having a mass ratio of hesperidin to hesperidin sugar adduct of 0.3 to 10.   The hesperidin composition according to claim 9, wherein the amount of hesperidin dissolved in water at 25 ° C is 1.3 g / L or more.   The hesperidin composition obtained by the production method according to any one of claims 1 to 8, wherein the mass ratio of hesperidin to hesperidin sugar adduct is 0.3 to 10.