WO2015083554A1

WO2015083554A1 - 4G-O-α-D-GLUCOPYRANOSYLRUTIN CRYSTAL AND APPLICATION THEREOF

Info

Publication number: WO2015083554A1
Application number: PCT/JP2014/080777
Authority: WO
Inventors: 渋谷　孝; 章子三宅
Original assignee: 株式会社林原
Priority date: 2013-12-02
Filing date: 2014-11-20
Publication date: 2015-06-11
Also published as: JPWO2015083554A1

Abstract

The problem addressed by the present invention is to provide a 4^G-α-glucosylrutin crystal, a 4^G-α-glucosylrutin crystal-containing powder, an application of same as a drug starting material, and applications as a cosmetic product starting material and a food product starting material. The problem is solved by providing a 4^G-α-glucosylrutin crystal configured from a ratio of one molecule of 4^G-α-glucosylrutin, one molecule of ethanol, and 8 molecules of water.

Description

Crystal of 4G-O-α-D-glucopyranosylrutin and its use

The present invention relates to a novel crystal of 4 ^G -O-α-D-glucopyranosylrutin, a crystal-containing powder containing the crystal, and use thereof.

Rutin is a glycoside having a structure in which β-rutinose (6-O-α-L-rhamnosyl-β-D-glucose) is bonded to the hydroxyl group at the 3-position of quercetin, which is one of flavonoids. Rutin is contained in flower buds of leguminous Enju, buckwheat buckwheat, and the like, and it is known that a large amount is contained in buckwheat seeds of varieties (see Patent Document 1). As a food containing rutin, buckwheat tea is widely used due to its health and palatability (see Patent Document 2). Rutin is also used in foods, pharmaceuticals, cosmetics and the like as a so-called vitamin P-like substance having physiological actions such as strengthening of capillaries, bleeding prevention, and blood pressure adjustment because rutin has a capillary contraction action. Furthermore, rutin is not just a vitamin P enhancer, but is involved in immune enhancement by increasing white blood cells, and plays an important role in maintaining and promoting the health of the body, so it can be used alone or in combination with other vitamins. It is used in foods and drinks as a yellow colorant and an antioxidant, and in cosmetics as a skin beautifier such as an ultraviolet absorber. Rutin is also used as a drug for the treatment of cerebral hemorrhage, hypertension, retinal hemorrhage, gastric pulmonary hemorrhage, hereditary telangiectasia, purpura, etc. as an anti-sensitive disease agent such as cardiovascular disease . However, rutin itself has a low solubility in water of about 10 mg / 100 ml (Non-patent Document 1) and is poorly water-soluble. It has been a problem for some time.

The present applicant has previously examined a derivative of rutin, and one molecule of glucose is bonded to the hydroxyl group at the 4-position of the glucose residue constituting β-rutinose in the rutin molecule through the following chemical formula: ⁴ G ^-O-α-D- glucopyranosyl rutin having the structure shown in 1 (hereinafter, abbreviated as ^"4 G-.alpha.-glucosyl rutin".) to create a such ⁴ G-.alpha.-glucosyl rutin Was found to be extremely water-soluble compared with rutin, and 4 ^G -α-glucosylrutin, its crystalline powder and its use were disclosed in Patent Document 3. This 4 ^G -α-glucosyl rutin is gradually decomposed by the action of a degradation enzyme (α-glucosidase) originally present in the living body, and finally is completely decomposed and metabolized to D-glucose and rutin. Therefore, it is considered safe to apply to humans.

Chemical formula 1:

However, at the time of Patent Document 3, a single crystal of 4 ^G -α-glucosyl rutin having properties sufficient to analyze the crystal structure has not been obtained yet, and disclosed in Patent Document 3 At most, the crystalline powder of 4 ^G -α-glucosyl rutin stops at the main diffraction angle (2θ) shown in powder X-ray diffraction. Non-patent document 2 also mentions a crystalline powder of 4 ^G -α-glucosyl rutin, but only the decomposition point has been reported. Thus, the crystal of 4 ^G -α-glucosylrutin whose crystal structure has been elucidated has not yet been reported as far as the applicant knows.

In general, a crystal of an organic compound is a group of molecules due to relatively weak intermolecular forces such as dispersion force and electrostatic interaction, and can take many metastable structures. Is conventionally known. Furthermore, it has been reported that organic compounds having a plurality of partial chemical structures tend to be polymorphic because the manner in which molecules are regularly arranged three-dimensionally tends to be one or more (Non-Patent Document 3). reference). In addition, if a solvated crystal (pseudocrystalline polymorph) in which a solvent is incorporated in the crystal is included, the combination becomes enormous, and therefore the number of crystal polymorphs discovered was spent on time and its search. It is said to be proportional to labor (see Non-Patent Document 4).

On the other hand, when viewed as a pharmaceutical material, the crystal structure of an organic compound is said to affect its solubility, absorbability, pharmacokinetics, physiological activity, and pharmacological effect. Even with the same organic compound, the crystal structure is different. The pharmacological effects, etc. are considered to differ greatly in suitability as a pharmaceutical material. Therefore, when considering the use of organic compounds as pharmaceutical materials, it is essential to elucidate the crystal structure. Conventionally, crystal polymorphism of the same compound has been studied and reported a lot (for example, non- (See Patent Document 5).

In this respect, 4 ^G -α-glucosylrutin is no exception, and in particular, 4 ^G -α-glucosylrutin is an organic compound having a plurality of partial chemical structures of quercetin, β-lutinose and glucose as described above. is naturally expected presence of crystalline polymorph, 4 to open up application as pharmaceutical raw material of ^{G-.alpha.-glucosyl} rutin, essential establishment of crystals of 4 ^{G-.alpha.-glucosyl} rutin crystal structure has been elucidated It is.

Japanese Patent Publication No. 5-63133 JP-A-60-262585 Japanese Patent No. 3194145

The present invention was made to solve the above-mentioned problems when 4 ^G -α-glucosyl rutin is used as a pharmaceutical material, and to pioneer the use of 4 ^G -α-glucosyl rutin as a pharmaceutical material. Novel crystals of 4 ^G -α-glucosylrutin whose structure has been elucidated, powders containing 4 ^G -α-glucosylrutin crystals containing the crystals, their use as pharmaceutical materials, cosmetic materials and food materials It is an object of the present invention to provide the use as

In order to solve the above problems, the present inventors first attempted to obtain 4 ^G -α-glucosyl rutin crystals by the method described in Patent Document 3. That is, in Patent Document 3, an 80% (v / v) ethanol solution is added to a freeze-dried solid (amorphous powder) of 4 ^G -α-glucosylrutin purified to 93%, heated and dissolved, and then seeded. 4 ^G -α-glucosyl rutin was added by a method of adding 0.5% (w / w) of crystals and allowing to stand at room temperature for 2 days to precipitate crystals, washing with 80% (v / v) ethanol solution and drying. Crystal powder is produced, and then vacuum-dried overnight at 80 ° C. to produce high-purity 4 ^G -α-glucosyl rutin powder (purity about 98%). However, when the crystallization method described in Patent Document 3 was reproduced, 4 ^G -α-glucosyl rutin crystallized only as a crystal in which minute needle-like crystals were fixed to each other as shown in FIG. Even if the crystals consist of a single crystal form, it was impossible to identify, and it was impossible to analyze the crystal structure of 4 ^G -α-glucosyl rutin using such crystals. .

Accordingly, as a result of further research efforts and repeated trial and error, the present inventors dissolved an amorphous powder having a purity of 4 ^G -α-glucosyl rutin of 95% or more in an ethanol aqueous solution of 70% (v / v) or less. Then, it was found that 4 ^G -α-glucosyl rutin crystals were precipitated when kept at low temperature, and the crystals were composed of a ratio of 1 molecule of 4 ^G -α-glucosyl rutin, 1 molecule of ethanol and 8 molecules of water. The present invention was completed by determining that the crystal was a completely unknown 4 ^G -α-glucosylrutin crystal that had not been previously known. Incidentally, the crystals of 4 ^G -α-glucosylrutin that have been successfully obtained by the present inventors have a diffraction angle different from the diffraction angle described in Patent Document 3 in powder X-ray diffraction, for example, as described later. It shows a main peak and is judged to be a crystal different from the crystal of 4 ^G -α-glucosyl rutin disclosed in Patent Document 3.

That is, the present invention solves the above problems by providing a 4 ^G -α-glucosyl rutin crystal composed of a ratio of one molecule of 4 ^G -α-glucosyl rutin, one molecule of ethanol and eight molecules of water. . A 4 ^G -α-glucosyl rutin crystal composed of at least such a molecular ratio has not been known before the filing of the present application, and the crystal is a novel crystal. Note that 4 ^G -α-glucosyl rutin crystals containing 4 ^G -α-glucosyl rutin molecules, ethanol molecules and water molecules in the above ratio are strictly called 4 ^G -α-glucosyl rutin solvate crystals. Although it may be, hereinafter, for the sake of convenience in this specification, it will be referred to as “4 ^G -α-glucosyl rutin crystal”, and the single crystal will be referred to as “4 ^G -α-glucosyl rutin single crystal”.

In addition, the 4 ^G -α-glucosyl rutin crystal of the present invention is, in detail, in powder X-ray diffractometry, the main characteristic diffraction angle (2θ) is 7.3 ° (Miller index (hkl): 020), It is a crystal showing 7.6 ° (Miller index: 021), 13.1 ° (Miller index: 025), 17.5 ° (Miller index: 008) and 18.3 ° (Miller index: 135).

The 4 ^G -α-glucosyl rutin crystal of the present invention more specifically has a crystal space group of C222 ₁ and unit cell lattice constants of a = 8.8337Å, b = 24.5552Å, c = It is a crystal belonging to orthorhombic system of 40.3391 and α = β = γ = 90 °.

In addition, crystals of 4 ^{G-.alpha.-glucosyl} rutin of the invention, 4 ^{G-.alpha.-glucosyl} rutin molecules, ethanol molecules, Table 2 or Table 3 carbon atoms, and oxygen atoms present specification constituting the water molecule A crystal having the atomic coordinates shown in FIG.

The 4 ^G -α-glucosyl rutin crystal of the present invention is, in one preferred embodiment, a crystal in the form of a single crystal.

The present invention also solves the above problem by providing a 4 ^G -α-glucosyl rutin crystal-containing powder.

Furthermore, the present invention solves the above problems by providing the 4 ^G -α-glucosyl rutin crystal of the present invention as a pharmaceutical material. That is, the 4 ^G -α-glucosylrutin crystals of the present invention, whose crystal structure has been elucidated, are easier to confirm the effectiveness and safety than the amorphous powders of 4 ^G -α-glucosylrutin, It is extremely useful as a pharmaceutical material.

In addition, the 4 ^G -α-glucosylrutin crystal-containing powder of the present invention can be obtained from a 4 ^G -α-glucosylrutin-containing solution by using the 4 ^G -α-glucosylrutin crystal of the present invention as a seed crystal. It can be obtained relatively easily without going through a recrystallization step. The 4 ^G -α-glucosylrutin crystal-containing powder of the present invention is relatively low in purity, but can be obtained without the need for a recrystallization step, and thus can be easily mass-produced. Therefore, the crystal-containing powder of 4 ^G -α-glucosyl rutin can be used as a cosmetic or food material as an inexpensive crystal-containing powder.

According to the 4 ^G -α-glucosyl rutin crystal of the present invention, since the crystal structure is clear, the physical and chemical properties of 4 ^G -α-glucosyl rutin necessary for use as a pharmaceutical material can be elucidated, There is an advantage that elucidation of polymorphism including the presence or absence of crystal polymorphism becomes extremely easy. In addition, when the 4 ^G -α-glucosyl rutin crystal of the present invention is used as a pharmaceutical material, it is safe because it is completely decomposed and metabolized into D-glucose and rutin in vivo. Therefore, the 4 ^G -α-glucosyl rutin crystal of the present invention is expected to have a pharmacological effect similar to that inherent to rutin, so that it can be used as a pharmaceutical material with extremely high water solubility compared to rutin. The advantage is that it can be used advantageously.

In addition, the 4 ^G -α-glucosylrutin crystal-containing powder of the present invention is necessary for high purity by using the 4 ^G -α-glucosylrutin crystal or single crystal of the present invention as a seed crystal as described above. It can be manufactured by omitting a plurality of recrystallization steps. Therefore, the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention has the same function as the 4 ^G -α-glucosyl rutin crystal of the present invention, and yield loss and process cost increase due to recrystallization. And can be manufactured relatively inexpensively. Therefore, in the fields of cosmetics manufacturing and food manufacturing using manufacturing plants designed on the assumption that powder raw materials are handled, other single or multiple powdered cosmetic materials, food materials, etc. fall under the pharmaceutical class The crystal of the present invention has an excellent advantage that it can be contained at a relatively low cost.

2 is an example of a micrograph of 4 ^G -α-glucosyl rutin crystals of the present invention obtained by crystallization using a 55% (v / v) aqueous ethanol solution. 2 is an example of a powder X-ray diffraction pattern of 4 ^G -α-glucosyl rutin crystals of the present invention. 3 is a stereomicrograph of 4 ^G -α-glucosyl rutin crystals (0.20 × 0.20 × 0.15 mm) used for X-ray crystal structure analysis. 2 is an example of a single crystal X-ray diffraction pattern of 4 ^G -α-glucosyl rutin crystals of the present invention. FIG. 4 is an ORTEP diagram of 4 ^G -α-glucosyl rutin excluding a hydrogen atom. FIG. 3 is a crystal structure diagram showing packing of 4 ^G -α-glucosyl rutin molecules in a crystal unit cell (a-axis direction). 2 is an example of a micrograph of 4 ^G -α-glucosyl rutin crystals obtained by a known method (the method described in Example A-6 of Patent Document 3).

1.4 ^G -α-glucosylrutin crystals The present invention is a novel crystal of 4 ^G -α-glucosylrutin composed of a ratio of 1 molecule of 4 ^G -α-glucosylrutin, 1 molecule of ethanol and 8 molecules of water, details In the powder X-ray diffraction method, the main characteristic diffraction angles (2θ) are 7.3 ° (Miller index (hkl): 020), 7.6 ° (Miller index: 021), 13.1 ° ( Miller index: 025), showing 17.5 ° (Miller index: 008) and 18.3 ° (Miller index: 135), more specifically, having a space group, lattice constant, and crystal system to be described later, The carbon atoms and oxygen atoms relate to crystals having atomic coordinates shown in Tables 2 to 3 below.

Unless 4 ^{G-.alpha.-glucosyl} rutin crystals of the present invention is a 4 ^{G-.alpha.-glucosyl} rutin crystals composed of 4 ^{G-.alpha.-glucosyl} rutin 1 molecule of ethanol per molecule and the ratio of water 8 molecules, the crystal Although it is not limited by the purity of 4 ^G -α-glucosyl rutin, it is usually 95% (w / w) or more, preferably 98% (w / w) or more, more preferably 99% (w / w). w) Those having a purity of 4 ^G -α-glucosyl rutin above are preferred. Unless otherwise specified, “%” represents mass percent (w / w).

As used herein, “4 ^G -α-glucosylrutin purity” means that a 4 ^G -α-glucosylrutin sample in the form of a solution, amorphous powder, crystal-containing powder, crystal, etc. is purified with purified water. Diluted or dissolved to 0.01% (w / v), filtered through a 0.45 μm membrane filter, subjected to HPLC analysis under the following conditions, and calculated from the total area of peaks appearing in the chromatogram at UV 255 nm. Means the area ratio (percentage) of 4 ^G -α-glucosyl rutin.

<HPLC analysis conditions>
HPLC device: “LC-20AD” (manufactured by Shimadzu Corporation)
Degasser: “DGU-20A3” (manufactured by Shimadzu Corporation)
Column: “CAPCELL PAK C18 UG120” (manufactured by Shiseido Co., Ltd.)
Sample injection volume: 10 μl
Eluent: water / acetonitrile / acetic acid (80/20 / 0.01 (volume ratio))
Flow rate: 0.7 ml / min Temperature: 40 ° C
Detection: UV detector “SPD-20A” (manufactured by Shimadzu Corporation)
Measurement wavelength: 255 nm
Data processing: “Chromatopack C-R7A” (manufactured by Shimadzu Corporation)

The 4 ^G -α-glucosylrutin single crystal of the present invention is directly analyzed by X-ray crystal structure analysis, that is, single crystal structure analysis by X-ray diffraction known to those skilled in the art (for example, Toshio Sakurai, “Guide for X-ray structure analysis”). ”, Published by Tokabo (1983), etc.), a single crystal X-ray diffraction pattern (diffraction spot) as illustrated in FIG. 4 to be described later can be obtained. Can do. For the single crystal structure analysis, a commercially available single crystal X-ray diffractometer, for example, an imaging plate single crystal automatic X-ray structure analyzer “R-AXIS RAPID” manufactured by Rigaku Corporation may be used. The X-ray diffractometer is preinstalled with computer software for structural analysis.

In the 4 ^G -α-glucosylrutin crystal of the present invention, the crystallographic parameters in the crystal are determined by the X-ray crystal structure analysis described above, and the atomic coordinates of each 4 ^G -α-glucosylrutin molecule (for each atom) And a three-dimensional structure model can be obtained. Specifically, the atomic coordinates of 4 ^G -α-glucosyl rutin are
(1) A step of irradiating a monochromatic X-ray onto the 4 ^G -α-glucosyl rutin crystal of the present invention to obtain an X-ray diffraction pattern;
(2) obtaining X-ray diffraction intensity data from the X-ray diffraction pattern;
(3) Direct method (program “SIR92”, A. Altomare et al., Journal of Applied Crystallography (J. Appl. Cryst.), 27, 435, (1994)) Obtaining an initial structure (electron density diagram) by:
(4) Based on the chemical structure of 4 ^G -α-glucosyl rutin, carbon atoms, oxygen atoms, and hydrogen atoms are assigned to the electron density map, and the structure is refined by the least square method so that the R value is minimized. The step of:
Can be obtained by a procedure comprising:

Incidentally, with respect to hydrogen atoms, if the size of the single crystal is relatively small and the X-ray diffraction intensity is weak, the atomic coordinates may not be determined. Even in such a case, 4 ^G -α-glucosyl rutin molecules can be obtained by molecular modeling based on the atomic coordinates of only non-hydrogen atoms (in the case of 4 ^G -α-glucosyl rutin, oxygen atoms and carbon atoms). The basic three-dimensional structure can be clarified.

Crystals of the invention, the space group of the crystals is C222 _1, the lattice constants of the unit cell a = 8.8337Å, b = 24.5552Å, a c = 40.3391Å, and, α = β = γ = It is a 90 ° orthorhombic crystal. The crystal of the present invention is not necessarily limited to a single crystal form as long as the crystal has the above space group, lattice constant, and crystal system.

More specifically, the 4 ^G -α-glucosyl rutin crystal of the present invention is more specifically the atomic coordinates shown in Tables 2 to 3 described below for each oxygen atom and each carbon atom of the 4 ^G -α-glucosyl rutin molecule in the crystal. And gives the ORTEP diagram shown in FIG.

2.4 from the 4 ^{G-.alpha.-glucosyl} rutin as a raw material for producing a 4 ^{G-.alpha.-glucosyl} rutin crystals TECHNICAL FIELD The present invention ^{G-.alpha.-glucosyl} rutin crystals is not particularly limited, obtained by organic synthesis Or obtained by an enzymatic synthesis method. Usually, a glycosyltransferase such as cyclomaltodextrin / glucanotransferase (hereinafter abbreviated as “CGTase”) is allowed to act on a partially degraded starch in the presence of rutin, followed by glucoamylase, followed by purification. Is suitable for the production of high purity 4 ^G -α-glucosyl rutin. The origin of CGTase is not particularly limited. For example, the genus Paenibacillus, Thermococcus, Thermoanaerobacter, Brevibacterium, Pyrococcus, Pyrococcus, Pyrococcus And CGTase derived from the genus Klebsiella, the genus Brevibacillus, the genus Saccharomyces, the genus Bacillus and the genus Geobacillus. Due to the high production rate of 4 ^G -α-glucosyl rutin, CGTase derived from Geobacillus stearothermophilus Tc-91 strain (National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center accession number FERM BP-11273) Is more preferable. 4 ^G -α-glucosyl rutin obtained by this enzyme synthesis method contains impurities derived from the production method.

The “contaminant derived from the production method” as used in the present specification refers to saccharides or rutin decomposed by dextrin as a production raw material, rutin glycosides other than 4 ^G -α-glucosylrutin, rutin degradation products, and rutin. It means other flavonoids. Contaminants can be separated by appropriately using a general purification method, that is, filtration, centrifugation, gel filtration, adsorption or ion exchange chromatography, and the like. Specifically, when producing purified 4 ^G -α-glucosyl rutin, 4 ^G -α-glucosyl rutin is separated from the above contaminants by utilizing the difference in adsorptivity by the porous synthetic adsorbent. And purified. The porous synthetic resin referred to in the present invention is a synthetic resin such as a nonionic styrene-divinylbenzene polymer, a phenol-formalin resin, an acrylate resin, and a methacrylate resin that is porous and has a wide adsorption surface area. For example, commercially available brand names manufactured by Rohm & Haas Amberlite XAD-1, Amberlite XAD-2, Amberlite XAD-4, Amberlite XAD-7, Amberlite XAD-8, Amberlite XAD-11, Amber Light XAD-12, trade names manufactured by Mitsubishi Kasei Kogyo Co., Ltd. Diaion HP-10, Diaion HP-20, Diaion HP-30, Diaion HP-40, Diaion HP-50, trade names manufactured by IMACTI Imakti Syn-42, Imakti Syn-44, There is such Makuti Syn-46.

In the method for purifying a reaction solution in which 4 ^G -α-glucosylrutin of the present invention is produced, when the reaction solution is passed through, for example, a column filled with a porous synthetic adsorbent, 4 ^G -α-glucosylrutin and comparison A small amount of unreacted rutin is adsorbed on the porous synthetic adsorbent, whereas a large amount of coexisting rutin glycoside and water-soluble saccharide flow out without being adsorbed. If necessary, after completion of the reaction of glycosyltransferase and before contacting with the porous synthetic adsorbent, for example, the reaction solution is heated to remove insoluble matter, or magnesium aluminate silicate, Treat with magnesium aluminate to adsorb and remove proteinaceous substances in the reaction solution, or treat with strongly acidic ion exchange resin (H type), medium basic or weakly basic ion exchange resin (OH type), etc. It is also optional to use a combination of purification methods such as desalting.

The high purity 4 ^G -α-glucosyl rutin used in the preparation of the 4 ^G -α-glucosyl rutin crystal of the present invention may be sufficiently pure to form crystals. The purity of 4 ^G -α-glucosyl rutin can be confirmed by the HPLC analysis described above. ⁴ G-.alpha.-glucosyl rutin purity as a raw material for producing the crystal is usually 95% or more, those preferably, 98% or more, more preferably having ⁴ G-.alpha.-glucosyl rutin purity of greater than 99% Is preferred.

Crystallization of an organic compound is usually performed based on the property that a solution containing the organic compound is brought into a supersaturated state to change from a dissolved state to an insoluble state and precipitate as crystals when a specific condition is satisfied. . The crystallization of 4 ^G -α-glucosyl rutin is specifically
(1) Add an aqueous ethanol solution to 4 ^G -α-glucosylrutin and dissolve at room temperature;
(2) Reduce the temperature of the solution in which 4 ^G -α-glucosyl rutin is dissolved to bring it into a supersaturated state;
(3) The supersaturated 4 ^G -α-glucosyl rutin solution is maintained at a constant temperature (eg, 4 ° C.) to precipitate crystals;
It can be done by the operation. Moreover, crystallization can also be accelerated | stimulated by adding a seed crystal as needed.

As the solvent used for preparing the crystal of the present invention, it is preferable to use an aqueous ethanol solution in which ethanol and water are mixed. When an ethanol aqueous solution is used as a solvent, the ethanol concentration is usually 70% (v / v) or less, preferably 60% (v / v) or less, more preferably 50 to 55% (v / v). . When the ethanol concentration is 80% (v / v) or more, although depending on the solid content concentration of the solution, it is preferable because crystals rapidly precipitate and crystals having a shape in which fine needle crystals are fixed to each other are preferable. Absent. Further, if the alcohol concentration is too low, there is a disadvantage that crystals do not precipitate or even if they are precipitated, it takes a long time for growth.

The temperature condition for crystallization is usually 0 to 40 ° C., preferably 0 to 30 ° C., more preferably 4 to 10 ° C., although it depends on the concentration of 4 ^G -α-glucosyl rutin and the ethanol concentration of the solvent. It is preferable.

The solid content concentration of the solution at the time of crystallization depends on the crystallization temperature and the ethanol concentration of the solvent, but is usually 40% (w / w) or less, preferably 30% (w / w) or less. Is preferably 15 to 20% (w / w).

3.4 ^G -α-Glucosylrutin Crystal-Containing Powder As used herein, “4 ^G -α-glucosylrutin crystal-containing powder” refers to a powder containing the 4 ^G -α-glucosylrutin crystal of the present invention described above. This means that the purity of 4 ^G -α-glucosyl rutin in such a crystal-containing powder can be appropriately selected according to the use of food, cosmetics, etc. as long as 4 ^G -α-glucosyl rutin crystals are included, Usually, 80% or more, more desirably 85.0% or more and less than 95.0% can be suitably used. Further, by powder X-ray diffraction, 7.3 ° (Miller index (hkl): 020), 7.6 ° (Miller index: 021), 13.1 ° (Miller index) as main characteristic diffraction angles (2θ). : 025) ^4G -α-glucosyl rutin crystal-containing powder showing 17.5 ° (Miller index: 008) and 18.3 ° (Miller index: 135).

4.4 ^{^G -α-} 4 ^{G -α-} glucosyl rutin as a raw material for producing a 4 ^{G-.alpha.-glucosyl} rutin crystal-containing powder the glucosyl rutin crystal-containing powder the manufacturing method of the present invention, the crystal-containing powder is formed minimum may be any purity deemed necessary, 4 ^{G-.alpha.-glucosyl} rutin content solution of the raw materials to 80% or more, it desirably those having 90% or more of 4 ^{G-.alpha.-glucosyl} rutin purity For example, the target 4 ^G -α-glucosyl rutin crystal-containing powder can be produced in a high yield with respect to the raw material.

The 4 ^G -α-glucosylrutin crystal-containing powder of the present invention is obtained by adding the 4 ^G -α-glucosylrutin crystal of the present invention as a seed crystal to a 4 ^G -α-glucosylrutin-containing solution that is not relatively high in purity. Can be obtained in high yield. Therefore, the 4 ^G -α-glucosyl rutin crystal-containing powder can omit a plurality of recrystallization steps required for the production process of a normal crystal product. Therefore, the 4 ^G -α-glucosylrutin crystal-containing powder of the present invention can be produced without loss of yield and increase in process cost due to recrystallization while having the same function as the crystal of the present invention. Therefore, in each field of food production including beverages using cosmetics designed to handle powder raw materials and cosmetic production, other single or multiple powdered food materials, cosmetic materials etc. It has an excellent advantage that it can be contained relatively inexpensively with respect to the corresponding crystal of the present invention.

5.4 4 ^{G-.alpha.-glucosyl} rutin crystal applications present invention as a medicament material ^{G-.alpha.-glucosyl} rutin crystals, similar to a conventional 4 ^{G-.alpha.-glucosyl} rutin, pharmaceutical material or quasi-drugs material Can be used as Examples of pharmaceuticals or quasi drugs include, for example, drinks, extracts, elixirs, capsules, granules, pills, eye ointments, oral mucosa patches, suspensions, emulsions, plasters, suppositories. Agents, powders, spirits, tablets, syrups, injections, tinctures, eye drops, ear drops, nasal drops, troches, ointments, fragrances, nasal sprays, limonades, liniments, Examples include flow extract, lotion, poultice, spray, coating agent, bath agent, patch, pasta agent, poultice. Moreover, it can also be set as the dosage form suitable for administration methods, such as rectal administration and injection, as needed. Furthermore, a pharmaceutical product or the like can be produced by using a general means on a pharmaceutical preparation in combination with a non-toxic pharmaceutical carrier.

Examples of the non-toxic pharmaceutical carrier include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, Examples include albumin, water, and physiological saline. In addition to non-toxic pharmaceutical carriers, conventional additives such as stabilizers, wetting agents, emulsifiers, binders, tonicity agents and the like can be appropriately added as necessary. The 4 ^G -α-glucosyl rutin crystal of the present invention has a clear crystal structure and extremely high purity. Therefore, the effectiveness and safety can be easily confirmed, and the hygroscopic property is low and the storage stability is good, so that it can be administered on a daily basis. Therefore, it is useful as a pharmaceutical material or a quasi-drug material.

When the 4 ^G -α-glucosyl rutin crystal of the present invention is used as a blood circulation improving agent, it may be used alone or in other physiology such as tocopherol, retinol acetate, pyridoxine hydrochloride, glycine, ethanol, nicotinic acid amide, licorice extract, or toki extract. It can be used as a composition with one or more of the active substances. In addition, when used as a nerve function regulator, alone or as necessary, a neuropsychiatric agent, an autonomic nerve agent, a sensory organ agent, fatty acids, vitamins, It can be used as a composition with one or more selected from minerals, herbal medicines, and interferons including interferon-α.

6.4 Use of ^G -α-glucosylrutin crystal-containing powder as a cosmetic material In recent years, aging proteins are generated and accumulated in the skin (dermis) due to aging, and skin troubles such as wrinkles, sagging, and yellowing are observed. What happens is reported. Usually, the skin is kept healthy by repeated decomposition and synthesis of proteins such as keratin and collagen (turnover), but aging proteins are modified (metabolized) because they are modified. It is hard to be done and will accumulate in the skin with aging. It is said that aging proteins are formed in the body mainly by two modification reactions. One is “Glycation” in which a sugar reacts with a protein, and the other is “carbonylation” in which a lipid peroxide reacts with a protein. It is known that active oxygen in the living body is deeply involved in these reactions.

“Saccharification” is also called Maillard reaction (brown change reaction), and means that reducing sugars such as glucose are non-enzymatically combined with dermal collagen and keratin of the stratum corneum to produce glycated protein. The produced glycated protein is also called advanced glycation end products (AGEs). In the AGE generation process, collagen and keratin are cross-linked intramolecularly and / or intermolecularly, resulting in physical and physiological changes (denaturation). Is caused.

“Carbonylation” means that lipid peroxides generated by lipid oxidation are further decomposed, resulting in highly reactive aldehydes (carbonyl compounds) such as acrolein, 4-hydroxy-2-nonenal, and malondialdehyde. It means that collagen, keratin and the like are non-specifically and non-enzymatically modified with a carbonyl compound to produce a carbonylated protein. The produced carbonylated proteins are also called lipid peroxidation end products (Advanced products: ALEs), and in the process of generating ALEs, collagen and keratin are cross-linked intramolecularly and / or intermolecularly, and physical and physiological changes ( Degeneration) is caused.

Here, 4 ^G -α-glucosyl rutin has a phenolic hydroxyl group, similarly to rutin, which is a kind of polyphenol. Since the phenolic hydroxyl group has radical scavenging activity, it exhibits an antioxidant effect by eliminating active oxygen, and thus suppresses the generation of active oxygen that is the cause of the above-mentioned “saccharification” reaction and “carbonylation” reaction.

The 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention can suppress a “saccharification” reaction or a “carbonylation” reaction by itself, but is not limited to known plant components having an inhibitory action on these reactions. Use in combination is also advantageous.

Known plant components having a saccharification reaction and a carbonylation reaction inhibitory effect include, for example, artichoke, ibrite, aomiz, akigumi, agrimony, agni fruit, akebi, acai fruit, ashwagandha, asunaro, asenyakunoki, abemakaki, amachiru, anise, American witch hazel, aristin, licorice, licorice, ginkgo, ichiyakusou, strawberry, yellow-bellied, white-necked turtle, dogbiwa, ipe bark, white-bellied maple, sardine-lily, fennel, witch hazel, wintergreen, turmeric, ume, vulgaricus, epimedium eboli Ezoukogi, Enishida, El Campule, Elder, Elba Mate, Pea, Syringa, Oubak, Auren, Milk Thistle, Oat, Oo Seaweed, Okahijiki, Otomeyuri, Onita, Oniyuri, olive, oregano, orange, pumpkin seeds, bonito bark, citrus lily, guarana, calcade, canaoi Ghetto, cowberry, snapper, salamander, pomegranate, sweet potato, salsaparilla, hawthorn, salamander, perilla, winged bean, shimotake, peonies, shrimp, white birch, birch, white cherry, white spruce, red sand , Red spider, dabira rugosa, tamoto lily, chadebugure, clove, chanoki, clove, cinneberry senna, clover, Izzy, dill, devil crow, swab, teppo lily, devil's claw root, tencha, tonin, dokudami, togenashi, tochu tea leaf, tomato, tormentilla, nagabishigishi, elderberry, nosenharen, nokongiku, mint, hakatayuri, hagi, flower Fruit, paffia root, rose, jackfruit, sunflower, sunflower, cornflower, sunflower, billaco, areca, buffalo, wisteria bean, grapes, black cohosh, safflower, mica, matababi, matils, pine, matebashi, mate tea Thistle's fruit, Maronier, Honeybee, Mobe, Mozuku, Yashajitsu, Willow, Yabukanzo, Yamatogebanreishi, Yamayuri, Yukinoshita, Yosai, Yomena Lychee seed, legal lily, ryukyuchiku, ryukyubara strawberry, apple immature, linden flower, rooibos, lettuce, lemon, lemongrass, lemon thyme, lemon verbena, lemon balm, rosehip, rose pink butts, rosemary, Plant extracts such as rose red, roman chamomile, laurel, rosea, logwood, walrus, lotus root, camellia leaf, licorice leaf, black soybean seed coat, black rice seed, moon peach leaf, fine leaf lily, western willow, cormorant leaf, tomorrow leaf leaf Things.

Also, as a skin problem, the occurrence of spots and freckles due to photoaging of the skin (dermis) has been attracting attention as a major problem for many years. Such photoaging symptoms are caused by repeated exposure to ultraviolet rays and infrared rays contained in sunlight for many years. Especially, stains develop the earliest, and the Japanese begin to appear on the face when they are over 40 years old.

The mechanism of the onset of spots and freckles is thought to be due to mutations in genes involved in melanin production in epidermal keratinocytes and pigment cells. Although the details of this mutation mechanism have not yet been clarified, it is considered that a mutation of a transcription factor that promotes expression of a keratinocyte gene (SCF) or a mutation of an SCF receptor in a pigment cell is involved. It is said.

Since 4 ^G -α-glucosyl rutin has an antioxidant action as described above, and also has an ultraviolet absorption property, it is effective against the gene mutation phenomenon as described above. Specifically, by preventing DNA damage of keratinocytes due to ultraviolet rays, it is expected to suppress the photoaging phenomenon (stains and freckles) of the skin as a result.

In other words, the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention suppresses the production of aging proteins that cause skin wrinkles, sagging, yellowing, and the like, and further causes horns and freckles. Since it exhibits the effect of preventing DNA damage of cells, it is extremely useful as an active ingredient of an anti-aging skin external preparation.

When the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention is used as an external preparation for skin, conventional auxiliary agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate are used as external preparations for skin. Sequestering agents such as sodium metaphosphate, gluconic acid, caffeine, tannin, verabamil, tranexamic acid and its derivatives, licorice extract, grabrizine, hot water extract of carin fruit, various herbal medicines, tocopherol acetate, glycyrrhizic acid and Drugs such as derivatives thereof or salts thereof, vitamin C, whitening agent such as magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid, sugars such as glucose, fructose, mannose, sucrose, trehalose, retinoic acid, retinol, Retinol acetate, palmi Vitamin A such as retinol tinate can be appropriately blended.

The 4 ^G -α-glucosylrutin-containing powder of the present invention can also be used as a cosmetic material in the same manner as conventional 4 ^G -α-glucosylrutin. The final product using the 4 ^G -α-glucosylrutin crystal-containing powder of the present invention as a cosmetic material is, for example, in the form of lotion, cream, emulsion, gel, powder, paste, block, soap, cosmetic soap, Chinese medicine Cleansing cosmetics such as soap, skin cleansing powder, facial cleansing cream, facial cleansing foam, facial rinse, body shampoo, body rinse, shampoo, rinse, hair wash powder, set lotion, hair blow, tic, hair cream, pomade, hair spray, hair liquid, Hair tonic, hair lotion, hair nourishing, hair dye, scalp hair treatment, lotion, vanishing cream, emollient cream, emollient lotion, pack cosmetic (jelly peel-off type, jelly-like wipe, paste-like wash , Cleansing cream, cold cream, hand cream, hand lotion, emulsion, moisturizer, after shaving lotion, shaving lotion, pre-shave lotion, after shaving cream, after shaving foam, pre-shave cream, cosmetic oil, Basic cosmetics such as baby oil, foundations (liquid, cream, solid, etc.), talcum powder, baby powder, body powder, perfume powder, make-up base, funny (cream, paste, liquid, solid, powder, etc.) ), Eyeshadow, eye cream, mascara, eyebrows, eyelash cosmetics, blusher, buccal lotion, and other makeup cosmetics, perfumes, perfumes, powdered perfumes, eau de cologne, perfume cologne, au Aromatic cosmetics such as toiletries, sun cream, sun lotion, sun oil, sun cream, sunscreen lotion, sunscreen oil, manicure, pedicure, nail color, nail lacquer, enamel remover, nail cream, nail makeup Nail cosmetics such as cosmetics, eyeliner cosmetics, lip cosmetics such as lipstick, lip balm, lipstick, lip gloss, oral cosmetics such as mouth odor inhibitor, toothpaste, mouthwash, bath salt, bath oil, bath cosmetics, etc. Examples include bath cosmetics. These cosmetics using the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention can be used on a daily basis because they are relatively pure and safe substances.

Further, the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention can be used in the form of a powder composition with other powdery cosmetic materials. Other powdery cosmetic materials to be mixed include, for example, white powder (talent), talc, kaolin, mica, sericite, starch, bentonite, silk powder, cellulose powder, nylon powder, bath salt, soap chips, titanium dioxide, Examples thereof include silicon dioxide (silica) and zinc oxide.

7.4 Use of ^G -α-glucosylrutin crystal-containing powder as food material The 4 ^G -α-glucosylrutin crystal-containing powder of the present invention is used as a food material in the same manner as conventional 4 ^G -α-glucosylrutin. be able to. The 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention is well harmonized with various substances having tastes such as sourness, salt to taste, astringency, umami, and bitterness, and has high acid resistance and heat resistance. It can be used as a general food or drink. For example, soy sauce, powdered soy sauce, miso, powdered miso, moromi, horsetail, flicker, mayonnaise, dressing, vinegar, three cups of vinegar, powdered sushi vinegar, Chinese food, tentsuyu, noodle soup, sauce, ketchup, grilled meat sauce, curry roux, stew Various types of seasonings such as nomoto, soup, dashi, composite seasoning, mirin, new mirin, table sugar, coffee sugar, potato chips, french fries, fried onion, corn chips, banana chips, vegetable chips, fried rice crackers , Fried confectionery such as university candy, kaki kempi, carinto, snacks, croquettes, cutlets, fried, tempura, fried chicken, fried satsuma, fried balls, fried chicken, spring rolls, fried noodles (instant noodles), rice crackers, arabe, dora Grilled, in the middle, bun, grilled octopus, takoyaki, wheat koshi, okoshi, carinto Various fermented Japanese sweets such as fertilizer, cocoons, manju, sea bream, sweet potatoes, water rams, brocade, jelly, castella, candy, biscuits, crackers, cookies, pie, pudding, pretzel, cereal, popcorn, cream puff , Waffles, sponge cakes, donuts, chocolate, chewing gum, caramel, candy and other Western confectionery, snack foods, bread, pizza, pie, sponge cake, waffles, castella, donuts and other processed wheat products, ice cream, sherbet and other ice confections , Fruit syrup pickles, ice syrups, butter cream, custard cream, flower paste, peanut paste, fruit paste spreads, pastes, jam, marmalade, syrup pickles, fructose fruit, vegetable processing Processed cereals such as goods, bread, noodles, cooked rice, artificial meat, grilled meat, yakitori, grilled pork, grilled fish, grilled rice balls, grilled rice cakes, fried rice, hamburger, dumplings, gratin, hayashi rice, curry rice, risotto, quiche, etc. Ready-made foods, salad oil, oils and fats such as margarine, pickles such as Fukujinzuke, bedara-zuke, Senkage-zuke, ryakyou-zuke, pickles such as takuan-zuke and Chinese cabbage, and meat products such as ham and sausage , Roasted eggs, fried eggs, broiled eggs, boiled eggs and other processed egg products, fish meat ham, fish sausage, fish products such as sea cucumber, chikuwa, hanpen, sea urchin, squid salted salt, vinegared kombu, suki-meme, fugu mirin Various delicacies such as dried, paste, wild vegetables, sea urchin, small fish, shellfish, etc., boiled beans, boiled beans, potato salad, kombu roll, heaven Salad foods such as pla, eggs such as tinsel eggs, milk drinks, butter, cheese, dairy products, fish, livestock meat, fruits, vegetables, bottles, canned foods, synthetic sake, brewed sake, fruit liquor, Western liquor, etc. Alcoholic beverages, amino acid beverages, peptide beverages, soy milk beverages, milk beverages, lactic acid beverages, fruit juice beverages, carbonated beverages, vegetable beverages, cocoa beverages, coffee beverages, juices, amazake, shiruko beverages, barley tea, hojicha, Chinese tea, tea, etc. Processed tea products and tea beverages, sweet chestnuts, peanuts, almonds, chocolate powder, coffee powder, coffee, cocoa, curry powder, rice balls, rice balls, rice barley, rice cakes, rice flour, roasted wheat germ food, roasted rice Roasted processed foods such as embryo foods, seasoned processed agricultural products, processed meat products, processed egg products, processed fishery products, foods and beverages such as bottles, canned foods, pudding mixes, hot cakes Health foods (functional foods), special-purpose foods (food for the sick, food for the elderly, food for childcare), specific health Foods for processing, processed materials such as gelling agents and swelling agents, preserved foods, emergency foods, space foods and the like. These foods and drinks mixed with the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention can be advantageously used for the purposes of vitamin P strengthening action, yellow coloring action, antioxidant action, quality improvement and the like.

Furthermore, the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention is used for the purpose of preventing discoloration or discoloration of natural pigments derived from fruits and the like, fruit juice beverages, powder beverages, boiled fruits, jams, jellies, It can be used to prevent deterioration of coffee flavors, citrus flavors and the like for bottles such as pastes and for the purpose of preventing oxidation. In addition, the 4 ^G -α-glucosylrutin crystal-containing powder of the present invention is used to prevent photodegradation and oxidation of vitamins, prevent deterioration of fat-containing foods such as confectionery and butter, increase the color of anthocyanin pigments, citrus juice It can be used for the purpose of preventing flavor deterioration of lactic acid bacteria beverages, preventing milk protein deterioration, preventing milk protein deterioration, preventing the sun odor of milk, preventing the deterioration of the flavor (flavor) of natural fruit juices and extracts, and improving shelf life.

In addition, the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention is composed of a conventionally known water-soluble antioxidant such as ascorbic acid, sodium ascorbate, catechin, chlorogenic acid, ferulic acid, carotenoid substances and vitamin E. When used in combination with oil-soluble antioxidants such as these, additive and synergistic antioxidant ability can be exhibited. Furthermore, the composition containing the 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention is suitable for functional foods and drinks for the purpose of improving lipid metabolism, suppressing blood sugar level increase, suppressing glycation, suppressing uric acid level increase, and strengthening blood vessels. Used.

The 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention can also be used in the form of a powdery composition with other powdery food materials. Other powdered food materials to be mixed include, for example, stevia extract, enzyme-treated stevia, Rahan fruit extract, L-aspartylphenyalanine methyl ester, acesulfame K, sucralose and other high-sweetness sweetener powders, sugar, Glucose, starch syrup, maltose, palatinose, trehalose, erythritol, sorbitol, maltitol, palatinit and other sugar powder and flour, starch, powdered sugar, powder seasoning, powder spice, powdered fruit juice, powdered fat, powdered peptide, powdered egg yolk, Examples include powdered milk, skim milk powder, powdered coffee, powdered cocoa, powdered miso, powdered soy sauce, and vegetable powder.

The 4 ^G -α-glucosyl rutin crystal-containing powder of the present invention is used for other purposes such as feeds and feeds for domestic animals such as livestock, poultry, bees, carp and fish, specifically cat foods and dog foods. It can also be used by blending with food for ornamental fish, food for farmed fish, etc. for the purpose of enhancing vitamin P, antioxidants, and palatability. Furthermore, it can be advantageously carried out by blending it into a plastic product or the like as an ultraviolet absorber or a deterioration preventing agent.

Hereinafter, the present invention will be described in more detail based on reference examples and examples. However, the following examples are given as preferred examples for carrying out the present invention, and the present invention should not be limited at all by these.

<Reference Example 1: Preparation of 4 ^G -α-glucosyl rutin amorphous powder>
5 parts by weight of rutin (special grade reagent, sold by Wako Pure Chemical Industries, Ltd.) is dissolved in a 6N sodium hydroxide solution, and dextrin (trade name “Paindex # 1”, sold by Matsutani Chemical Co., Ltd., moisture 7. 7%) was added, and each was added to ₂ mM CaCl ₂ aqueous solution so that the concentration was 15% (w / v), heated to 50 ° C., and stirred to completely dissolve. . After adjusting the pH of the solution to 9.0 using hydrochloric acid, it was derived from Geobacillus stearothermophilus Tc-91 strain (National Institute of Advanced Industrial Science and Technology, Patent Biodeposition Center accession number FERM BP-11273) 100 units of CGTase was added per 1 g of dextrin, and the enzyme reaction was carried out at 50 ° C. for 24 hours. Next, the enzyme was inactivated by heat treatment at 100 ° C. for 10 minutes, adjusted to pH 4.0 using 6N hydrochloric acid, and glucoamylase (trade name “XL-4”, sold by Nagase ChemteX Corporation) was added thereto. Then, 20 units per 1 g of solid content of dextrin was added and reacted at 50 ° C. for 24 hours. After the reaction, the enzyme reaction was stopped by treatment at 100 ° C. for 10 minutes. Activated carbon was added to the reaction solution, treated at 60 ° C. for 1 hour, and then filtered through diatomaceous earth. The obtained filtrate was applied to a column packed with an adsorption resin (“HP-20”, manufactured by Mitsubishi Chemical), adsorbed rutin and rutin glucoside on the resin, washed with water, and then washed with 50% (v / v ) Rutin and rutin glucoside were eluted using an aqueous ethanol solution. The eluate was concentrated, purified using activated carbon and an ion exchange resin, and then spray-dried to prepare 300 g of 4 ^G -α-glucosylrutin-containing amorphous powder. This product contained about 88% of 4 ^G -α-glucosyl rutin.

Reference Example 2: Preparation of high purity 4 ^G -α-glucosyl rutin crystalline powder
It was added 150g of 80% (v / v) aqueous ethanol solution in ⁴ G-.alpha.-glucosyl rutin containing amorphous powder ⁽⁴ G-.alpha.-glucosyl rutin purity 88%) 100 g prepared in Reference Example 1, dissolved by heating, Stored at 25 ° C. for 2 days. The produced crystal was recovered by filtering the crystal suspension, and vacuum dried at room temperature for 2 hours to prepare 70 g of crystalline powder. Such a crystallization step was repeated several times to prepare about 21 g of high purity 4 ^G -α-glucosyl rutin crystalline powder (purity 97.4%).

<Preparation of 4 ^G -α-glucosyl rutin crystals>
70 g of 60% (v / v) aqueous ethanol solution was added to 10 g of 4 ^G -α-glucosyl rutin crystalline powder prepared in Reference Example 2 and dissolved, and then allowed to stand at 4 ° C. for 1 week for crystallization. The crystallized crystals were collected by a glass filter, washed with a small amount of 75% aqueous ethanol, and then vacuum-dried at room temperature for 2 hours. By this series of operations, 59.6 g of ^4G -α-glucosyl rutin crystals having a purity of 99.6% were obtained in a yield of 52% based on the raw material. The obtained crystal was designated as test sample 1.

<Preparation of 4 ^G -α-glucosyl rutin crystal-containing powder>
To ⁴ G-.alpha.-glucosyl rutin containing amorphous powder ⁽⁴ G-.alpha.-glucosyl rutin purity 88%) 100 g prepared in Reference Example 1, 70% (v / v ) aqueous ethanol solution 150g was added, dissolved by heating Further, 1.0 g of the test sample 1 prepared in Example 1 was added and mixed as a seed crystal, and then allowed to stand at 25 ° C. for 48 hours for crystallization. The crystallized crystals were recovered by filtering the crystal suspension, washed with a small amount of 75% aqueous ethanol solution, and then vacuum-dried at room temperature for 2 hours to obtain 4 ^G -α-glucosylrutin crystal-containing powder (purity 93. 4%) was prepared in an amount of 62 g. The obtained crystal-containing powder was used as test sample 2.

<Various analyzes of 4 ^G -α-glucosyl rutin crystals>
Using the test sample 1 prepared in Example 1, the physical properties shown below were measured and analyzed.

(1) Crystal photograph A photograph of the test sample 1 taken using an inverted microscope (“TMS-F type”, manufactured by JASCO Corporation) is shown in FIG. As can be seen from FIG. 1, the crystals prepared in Example 1 were compared with crystals prepared by a known method (the method described in Example A-6 of Patent Document 3) (see FIG. 7). It can be seen that many large columnar crystals are included.

(2) Powder X-ray diffraction Using a powder X-ray diffractometer (“X'Pert Pro MPD”, manufactured by Spectris Co., Ltd.), about 50 mg of the test sample 1 was placed on a silicon non-reflective plate and rotated while facing the Cu counter cathode. A powder X-ray diffraction pattern was determined by a reflection method using CuKα rays (X-ray tube current 40 mA, X-ray tube voltage 45 kv, wavelength 1.5405 mm), which is characteristic X-rays radiated from the X-ray tube. The powder X-ray diffraction pattern of the test sample 1 is shown in FIG. As shown in FIG. 2, test sample 1 has 7.3 ° (Miller index (hkl): 020), 7.6 ° (Miller index: 021), 13.1 ° (main characteristic diffraction angle (2θ)). The diffraction peaks were shown at Miller index: 025), 17.5 ° (Miller index: 008) and 18.3 ° (Miller index: 135). The main characteristic diffraction angles (2θ) of the crystal described in Patent Document 3 are 4.4 °, 8.4 °, 11.5 °, 18.2 ° (Example A- of Patent Document 3). 4), or 6.8 °, 8.1 °, 15.4 °, 17.8 ° (Example A-6 of Patent Document 3), and the 4 ^G -α-glucosylrutin crystals of the present invention The diffraction angle of the main peak is clearly different. Therefore, the 4 ^G -α-glucosyl rutin crystal of the present invention is a novel crystal different from the crystalline 4 ^G -α-glucosyl rutin obtained in Patent Document 3. In addition, when the powder X-ray diffraction pattern was similarly obtained for test sample 2, the same main characteristic diffraction angle (2θ) as test sample 1 was shown.

<Preparation of 4 ^G -α-glucosyl rutin single crystal>
11 g of 55.0% (v / v) ethanol aqueous solution was added to 2 g of 4 ^G -α-glucosyl rutin crystals (test sample 1) prepared in Example 1, stirred and dissolved, and this was kept at 4 ° C. for 20 days. It crystallized out.

Under a stereomicroscope connected with a digital microscope (“GBX100”, manufactured by Nakaden Co., Ltd.), crystals of appropriate size were collected from the crystallized 4 ^G -α-glucosylrutin crystals and immediately coated with Palaton oil. After that, it was mounted on a sample holder and used as a sample for X-ray crystal structure analysis (test sample 3).

From the remaining crystal suspension from which the crystals for X-ray crystal structure analysis were collected, the crystals collected by the glass filter were dried to obtain about 0.45 ^g of 4 ^G -α-glucosyl rutin crystals. The purity of 4 ^G -α-glucosyl rutin of the crystals was 100%. Thereby, it is predicted that the test sample 3 is a single crystal having a very high purity. Moreover, when powder X-ray diffraction of the crystal was performed, the X-ray diffraction pattern showed the same diffraction pattern as that of the test sample 1.

<X-ray crystal structure analysis of single crystal of 4 ^G -α-glucosyl rutin>
The test sample 3 prepared in Example 4 was mounted on a sample holder and then set in a single crystal X-ray diffractometer (“R-AXIS RAPID-R”, manufactured by Rigaku Corporation), and a nitrogen gas (−170 ° C.) atmosphere Below, the X-ray diffraction pattern of the crystal was measured by vibration photography under the following conditions.

<X-ray diffraction pattern measurement conditions>
X-ray source: Cu
Output: 50kV, 100mA
Incident X-ray: CuKα ray (λ = 1.54187Å)
Incident X-ray size: about 0.5mmφ
Crystal size: 0.20 × 0.20 × 0.15mm
Detector: Imaging plate Measurement temperature: Approximately -170 ° C (nitrogen gas blowing method)

A stereoscopic micrograph of a single crystal of 4 ^G -α-glucosylrutin used for X-ray crystal structure analysis is shown in FIG. 3, and an example of the X-ray diffraction pattern is shown in FIG.

In the X-ray diffraction pattern, many diffraction spots (spots) were confirmed, and it was confirmed that the crystal was a single crystal. Although the shape of the X-ray diffraction spot was relatively good, its intensity was weak. Of the 60,575 reflections (diffraction) observed, there were 8,388 unique reflections.

Based on the X-ray diffraction intensity of the X-ray diffraction pattern, the initial structure is obtained by a direct method, and a structural model is created with reference to the structural formula of 4 ^G -α-glucosylrutin, and further, based on 3,691 reflections. Refined by least squares method. As analysis software, “Crystal Structure Ver.” Manufactured by Rigaku Corporation. 4.0.1 "was used. Table 1 summarizes the crystallographic data of 4 ^G -α-glucosylrutin obtained by X-ray crystal structure analysis.

As shown in Table 1, from the obtained X-ray diffraction intensity data, crystal system belongs crystals, orthorhombic (orthorhombic), space group is C222 _1, the lattice constants, a = 8.8337Å, b = 24.5552Å, a c = 40.3391Å, α = β = γ = 90 °, was determined to V = 8750.1Å ^3. Further, Z value representing the number of molecules of 4 ^{G-.alpha.-glucosyl} rutin per unit cell of the crystal becomes 8, in the present crystals, contains 4 ^{G-.alpha.-glucosyl} rutin 8 molecules per unit cell of the crystal It has been found.

<Analysis of molecular structure and crystal structure>
As a result of analysis by the direct method, the hydrogen atom in the 4 ^G -α-glucosyl rutin molecule could not be identified, but the basic skeleton of the non-hydrogen atom (carbon atom and oxygen atom) was 4 ^G -α-glucosyl. Based on the structural information of rutin, elements could be arranged at each atomic position. The atomic coordinates (x, y, z) of each oxygen atom and carbon atom in the 4 ^G -α-glucosyl rutin molecule obtained by refining the coordinate data and the values of the respective isotropic temperature factors (Beq) are shown in Table 2 and The results are shown in Table 3 (continuation of Table 2).

Further, FIG. 5 shows an ORTEP diagram of the 4 ^G -α-glucosyl rutin crystal molecule of the present invention calculated and displayed from the refined coordinate data. In addition, the packing structure of the 4 ^G -α-glucosyl rutin crystal molecules of the present invention per unit cell of the crystal is shown in FIG. 6 as a crystal structure diagram when viewed from the a-axis direction. The numbers of oxygen atoms and carbon atoms in Tables 2 and 3 respectively correspond to the numbers of oxygen atoms and carbon atoms described in the ORTEP diagram of the 4 ^G -α-glucosylrutin crystal molecule of the present invention in FIG. Yes. Moreover, the numerical value in the parenthesis of each numerical value in Table 2 and Table 3 means a standard deviation.

In the ORTEP diagram shown in FIG. 5, carbon numbers C1 to C15 and oxygen numbers O1 to O7 represent the structure of quercetin in the 4 ^G -α-glucosylrutin molecule, carbon numbers C16 to C27 represent the structure of β-lutinose, Carbon numbers C28 to C33 represent the structure of glucose bonded via the α-glucoside bond to the hydroxyl group at the 4-position of the glucose residue constituting the β-lutinose structure. Further, the carbon numbers C34 to C35 and the oxygen number O22 represent that one molecule of ethanol is contained, and the oxygen numbers O23 to O30 represent that eight molecules of water are contained. That is the crystalline 4 ^{G-.alpha.-glucosyl} rutin 1 molecule of ethanol 1 molecules and 4 ^{G-.alpha.-glucosyl} rutin formed by the ratio of water 8 molecular crystal. On the other hand, from the crystal structure diagram shown in FIG. 6, it can be well understood that in this crystal, 8 molecules of 4 ^G -α-glucosyl rutin are packed per unit cell. In addition, in the crystal structure diagram of FIG. 6, there are apparently many 4 ^G -α-glucosyl rutin molecules because molecules packed in other unit cells adjacent to the unit cell are also displayed. is there.

<Acute toxicity test>
The test sample 1 prepared in Example 1 was orally administered once to a 5-week-old ddy mouse that had been fasted for 4 hours before the test, once per mouse weight, and the onset of toxic symptoms The degree was observed over time. As a result, no abnormality was observed in all mice for 14 days, and the result of dissection was not abnormal. Therefore, LD ₅₀ was determined to be 1,500 mg / kg or more. Therefore, it can be said that 4 ^G -α-glucosyl rutin of the present invention has extremely low toxicity and can be safely administered to mammals.

<Melting point measurement>
Using 4 ^G -α-glucosylrutin crystal powder (test sample 1) and 4 ^G -α-glucosylrutin amorphous powder (control) prepared in Reference Example 1, the melting point and decomposition point were measured under the following conditions. did.

Melting point and decomposition point were measured using a melting point measuring instrument (“Model MP-21”, manufactured by Yamato Chemical Co., Ltd.). After filling the sample with a capillary (φ1.0 × 1.55 × 80 mm, cantilevered type, manufactured by Nihon Riken Kikai Co., Ltd.) with about 3 mg, the temperature is gradually raised from room temperature at a heating rate (5 ° C./min). Yuki, the state of the powder sample was observed with the naked eye. The temperature at which melting of the solid powder was clearly recognized was taken as the melting point, and the temperature at which it was carbonized black by heating was taken as the decomposition point. Table 4 shows melting points and decomposition points of both samples.

The control amorphous powder did not show a clear melting point, began to blacken at around 232 ° C., and completely carbonized and decomposed at 235 ° C. On the other hand, test sample 1 melted at around 93-95 ° C., and when further heated, it carbonized black and decomposed at around 239-241 ° C. Note that the decomposition point of crystalline 4 ^G -α-glucosyl rutin described in Non-Patent Document 2 is 232 to 235 ° C., which is different from the decomposition point of the 4 ^G -α-glucosyl rutin crystal according to the present invention. As described above, the 4 ^G -α-glucosylrutin crystal of the present invention is a novel crystal clearly distinguished from the conventionally known 4 ^G -α-glucosylrutin powder even from the viewpoint of the decomposition point.

<Dynamic moisture adsorption amount>
For 4 ^G -α-glucosylrutin crystal powder (test sample 1) and 4 ^G -α-glucosylrutin amorphous powder (control) prepared in Reference Example 1, the dynamic water adsorption amount was measured under the following conditions. .

The measurement of the dynamic moisture adsorption amount was performed using a moisture adsorption / desorption measuring device (“IGAsorp”, manufactured by HEIDEN). In the apparatus, a powder sample (about 20 mg) filled in a mesh holder was allowed to flow with 99.9% purity nitrogen gas at a flow rate of 250 ml / min for 1 hour, and then the dry weight of the sample was measured. The weight of the sample adsorbed with water was measured by increasing and changing the temperature stepwise (60.0, 75.2, 84.2 and 90.1) starting from 6 ° C. and a relative humidity of 60.0%. The humidity condition was set so that the sample was held for a minimum of 1 hour under each relative humidity condition and then reached the next relative humidity when the sample weight reached equilibrium at a constant weight or after 24 hours. .

Table 5 shows the results of calculating the weight increase rate under each relative humidity condition based on the weight under the condition of 60.0% relative humidity. Further, Table 5 also shows the form of the powder after being held at a relative humidity (RH) of 90.1% at the final stage.

As shown in Table 5, the weight increase rate of the 4 ^G -α-glucosyl rutin amorphous powder after the dynamic moisture adsorption test was about 14%, whereas the 4 ^G -α-glucosyl rutin of the present invention was about 14%. That of the crystals was as low as less than 7%. In addition, the 4 ^G -α-glucosylrutin amorphous powder after the test showed a viscous liquid form, whereas the 4 ^G -α-glucosylrutin crystals of the present invention still maintained the powder form. It was. This result shows that the control 4 ^G -α-glucosylrutin amorphous powder absorbs moisture and deliquesces, whereas the 4 ^G -α-glucosylrutin crystals of the present invention are crystals. Therefore, it shows relatively low hygroscopicity and is stable as a powder.

<Tablets>
Ascorbic acid 2-glucoside (Hayashibara registered trademark “AA2G”) 20 parts by mass of crystalline β-maltose 13 parts by mass, corn starch 4 parts by mass and 4 ^G -α-glucosylrutin crystals 3 prepared by the method of Example 1 After mass parts were mixed uniformly, tableting was performed to obtain tablets.

This product is a complex vitamin preparation of 4 ^G -α-glucosylrutin and ascorbic acid 2-glucoside, and it is a tablet that has good ascorbic acid stability and is easy to drink.

<Liquid>
6 parts by weight of sodium chloride, 0.3 parts by weight of potassium chloride, 0. 2 parts by mass, 3.1 parts by mass of sodium lactate, 44 parts by mass of trehalose (registered trademark “Treha”, Hayashibara Co., Ltd.), 2 parts by mass of 4 ^G -α-glucosylrutin crystals prepared by the method of Example 1 and ascorbic acid 2 -0.5 part by weight of glucoside (Hayashibara registered trademark “AA2G”) is dissolved in 1,000 parts by weight of purified water, filtered through a membrane according to a conventional method, and then filled in 30 ml sterilized plastic containers. A solution containing 4 ^G -α-glucosyl rutin was obtained.

This product combines vitamins, calories, and minerals, and is useful as eye drops and injections for treating diseases associated with eye strain and severe muscle stiffness.

<Capsule>
10 parts by mass of calcium acetate / monohydrate, 50 parts by mass of L-magnesium lactate / trihydrate, 57 parts by mass of maltose, 20 parts by mass of 4 ^G -α-glucosylrutin crystals prepared by the method of Example 1 and eicosapentaenoic acid 12 parts by mass of 20% -containing γ-cyclodextrin inclusion compound was uniformly mixed and granulated by a granulator, and then encapsulated in a gelatin capsule according to a conventional method to produce a capsule containing 150 mg per capsule. .

This product can be advantageously used as a high-quality blood cholesterol lowering agent, immunostimulant, skin beautifier, sensitive disease preventive agent, therapeutic agent, food for health promotion, and the like.

<Injection solution for use>
1 part by mass of a single crystal of 4 ^G -α-glucosyl rutin prepared by the method of Example 4 and 99 parts by mass of glucose as an extender were dissolved in water, purified and filtered according to a conventional method to make pyrogen-free, and this solution Was dispensed to a 20 mL ampoule to give 100 mg of 4 ^G -α-glucosylrutin, freeze-dried and sealed to produce an injection.

The injection can be administered alone or mixed with other vitamins, minerals, etc., intramuscularly or intravenously. In addition, this product does not need to be stored at a low temperature and has extremely good solubility in physiological saline and the like when used. This product is effective not only as vitamin P supplement, but also as an antioxidant to remove active oxygen and suppress the formation of lipid peroxide, and various other diseases such as viral diseases, bacterial diseases, cardiovascular diseases, malignant tumors, etc. It can be advantageously used as a prophylactic or therapeutic agent for diseases.

<Solid formulation>
To 20 parts by mass of 4 ^G -α-glucosyl rutin crystals prepared by the method of Example 1, 70 parts by mass of sucrose, 10 parts by mass of dextrin, and an appropriate amount of flavoring were added, and the mixture was stirred and mixed using a mixer. ^{A G} -α-glucosyl rutin solid preparation was prepared.

This product is a rutin solid preparation that can be easily mixed with other food ingredients and is less susceptible to browning or consolidation even after long-term storage. Since this product or a composition containing the same exhibits the physiological function of rutin in vivo, it can be taken orally as a nutritional food preparation. Furthermore, this product is a solid preparation that also has an inhibitory action on the formation of glycation end products (AGEs) that cause diabetic vascular disorders.

<Oral tube feeding agent>
Crystalline α-maltose 20 parts by mass, glycine 1.1 parts by mass, sodium glutamate 0.18 parts by mass, sodium chloride 1.2 parts by mass, citric acid 1 part by mass, calcium lactate 0.4 parts by mass, magnesium carbonate 0.1 A formulation comprising 0.1 part by mass of 4 ^G -α-glucosylrutin single crystal prepared by the method of Example 4, 0.01 part by mass of thiamine and 0.01 part by mass of riboflavin was prepared. Each 24 g of this blend was filled into a laminated aluminum sachet and heat sealed to prepare an oral tube feeding.

This oral tube feeding agent is dissolved in about 300 to 500 ml of sterile water in a bag, and can be advantageously used as an oral feeding solution or a tube feeding solution for the nasal cavity, stomach, intestine and the like.

<Ointment>
1 part by mass of sodium acetate / trihydrate and 4 parts by mass of calcium lactate were mixed uniformly with 10 parts by mass of glycerin, and this mixture was mixed with 50 parts by mass of petroleum jelly, 10 parts by mass of wax, 10 parts by mass of lanolin, and 14.5 of sesame oil. In addition to a mixture of 1 part by mass of 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2 and 0.5 part by mass of mint oil, the mixture was further uniformly mixed to produce an ointment.

This product has anti-oxidant properties, high stability, and can be advantageously used as a high-quality sunscreen, skin beautifier, whitening agent, and further as a healing accelerator for wounds and burns.

<Bath agent>
21 parts by mass of DL-sodium lactate, 8 parts by mass of sodium pyruvate, 5 parts by mass of 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2 and 40 parts by mass of ethanol, 26 parts by mass of purified water and coloring A bath preparation was prepared by mixing with appropriate amounts of fragrance and fragrance.

This product can be diluted 100-10,000 times in hot water for bathing and used as a bathing agent. Furthermore, this product has a beautifying skin and fair skin effect, and can be used by appropriately diluting it with water for washing face, lotion and the like.

<Emulsion>
0.5 parts by mass of polyoxyethylene behenyl ether, 1 part by mass of polyoxyethylene sorbitol tetraoleate, 1 part by mass of lipophilic glyceryl monostearate, 0.5 parts by mass of pyruvic acid, 0.5 parts by mass of behenyl alcohol, avocado oil 1 part by weight, 1 part by weight of 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2, vitamin E and appropriate amounts of preservatives were dissolved by heating in accordance with a conventional method, and 1 part by weight of L-sodium lactate was added thereto. 1,5 parts by weight of 1,3-butylene glycol, 0.1 part by weight of carboxyvinyl polymer and 85.3 parts by weight of purified water were added and emulsified with a homogenizer. Further, an appropriate amount of a perfume was added and mixed with stirring to produce an emulsion. .

This product can be used advantageously as an emulsion for sunscreen, spots and freckles, beautiful skin and fair skin, and also inhibits the generation of AGEs and ALEs and should be used as an emulsion for preventing wrinkles, sagging and dullness. Can do.

2 parts by weight of polyoxyethylene glycol monostearate, 5 parts by weight of self-emulsifying glyceryl monostearate, 2 parts by weight of powder containing 4 ^G -α-glucosyl rutin crystals obtained by the method of Example 2, 1 part by weight of liquid paraffin, 10 parts by mass of glyceryl trioctanoate and an appropriate amount of an antiseptic are dissolved by heating according to a conventional method, and 2 parts by mass of L-lactic acid, 5 parts by mass of 1,3-butylene glycol and 66 parts by mass of purified water are added to the homogenizer and emulsified. Further, an appropriate amount of a fragrance was added and mixed with stirring to produce a cream.

This product has antioxidant properties, high stability, can be advantageously used as a high-quality sunscreen, stain / freckle-preventive, beautiful skin, fair skin cream, and also inhibits the generation of AGEs and ALEs. It can be advantageously used as a cosmetic cream for preventing wrinkles, sagging and dullness.

<Lemon flavor>
After adding 500 g of 65% (v / v) ethanol to 50 g of lemon oil and stirring the mixture at room temperature for 10 minutes, the upper terpene layer separated by allowing to stand is removed, and the ethanol layer is filtered through a filter paper to give 495 g of lemon flavor. Got. 0.04% by mass of the 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2 was added and dissolved in the obtained lemon flavor to prepare a lemon flavor excellent in storage stability.

Since this product contains 4 ^G -α-glucosylrutin, it has enhanced vitamin P-like action, no deterioration of the flavor and off-flavor of lemon, and excellent storage stability. Lemon flavor.

<Chewing gum>
3 parts by weight of gum base is melted by heating until soft, 7 parts by weight of powdered green-yellow vegetable having a trehalose content of about 50% (w / w) is added thereto, and together with appropriate amounts of coloring and flavoring, the method of Example 2 4 ^G -α-glucosylrutin containing powder obtained in 1 above was added to a solid content of 0.1%, and then kneaded, molded and packaged by a conventional method to contain 4 ^G -α-glucosylrutin A chewing gum was obtained.

This product with good texture and taste is useful as a chewing gum to improve and maintain blood circulation and to relieve or prevent muscle stiffness associated with stiff shoulders, low back pain, and muscle pain.

<Health food>
4 ^G obtained by the method of Example 2 as skim milk 85 parts by weight, skim milk powder 3 parts by weight, trehalose (Hayashibara registered trademark “Treha”) 6 parts by weight, agar 0.1 parts by weight, glycosylated vitamin Ps -3 parts by weight of α-glucosyl rutin crystal-containing powder, 4 parts by weight of powdered sugar-transferred hesperidin, 1 part by weight of blueberry extract and 2 parts by weight of purified water are placed in a preparation tank and heated to 55 ° C with stirring to completely dissolve. did. Next, the mixture is homogenized according to a conventional method, sterilized by a sterilization cooler, inoculated with 3% (w / w) starter, filled in a plastic container, and then fermented at 37 ° C. for 5 hours to give sugar-transfer vitamin P. The yogurt type health food contained was obtained.

This product with good flavor and taste is useful as a health food to improve and maintain blood circulation and to relieve or prevent muscle stiffness associated with stiff shoulders, low back pain, and muscle pain. In addition, this product is a yogurt-type health food that has the function of preventing the degradation of milk protein, preventing the fading of natural pigments derived from blueberries.

<Lactic acid bacteria beverage>
175 parts by weight of skim milk powder, 30 parts by weight of 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2 and lactosucrose-rich powder (Hayashibara Co., Ltd., “milk oligo”) were added to 1,500 water Dissolve in parts by mass, sterilize at 65 ° C. for 30 minutes, cool to 40 ° C., inoculate 30 parts by mass of a starter of lactic acid bacteria, and then incubate at 37 ° C. for 8 hours to obtain a lactic acid bacteria beverage It was.

This product contains 4 ^G -α-glucosylrutin and oligosaccharides that have vitamin P-like action, and it not only keeps lactic acid bacteria stable, but also has bifidobacterial growth-promoting action and intestinal regulation action, and milk protein It is a lactic acid bacteria beverage in which the flavor is well maintained for a long time.

<Health supplement>
1 part by mass of 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2 and 99 parts by mass of trehalose (Tradeha, Hayashibara, registered trademark) were mixed uniformly, and 50 g each was filled into a glass bottle. The product.

This product with excellent solubility and handling is useful as a health supplement to improve and maintain blood circulation and to relieve or prevent muscle stiffness associated with stiff shoulders, low back pain, and muscle pain.

<Boiled buffalo>
Peel off the Japanese cypress, cut it into an appropriate length, and immerse it in a thin saline solution for several hours. This is mixed with 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2 and Blue No. 1. Then, it was boiled with a liquid containing a green colorant prepared to obtain a boiled green brilliant buffalo.

This product adds color as a material for various Japanese dishes and also exhibits physiological effects as dietary fiber.

<Fertilization>
1.2 parts by weight of water is mixed with 1 part by weight of glutinous seed starch and gelatinized by heating, and 1.5 parts by weight of sugar and 0.7 parts by weight of crystalline β-maltose (Hayashibara Co., Ltd., “Sun Malt”) Part, 0.3 part by weight of starch syrup, and 0.2 part by weight of 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2, and thereafter molding and packaging according to conventional methods to produce fertilizer did.

This product is a Kibidango-style Japanese confectionery with good fertilization and good taste and taste.

<Mixed sweetener>
100 parts by weight of honey, 50 parts by weight of isomerized sugar, 2 parts by weight of brown sugar and 1 part by weight of 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2 were mixed to obtain a mixed sweetener.

This product is a sweetener with enhanced vitamin P-like action and is suitable as a health food.

<Hard candy>
1,500 parts by weight of reduced maltose starch syrup is heated and concentrated under reduced pressure to a water content of about 2% or less. To this, 15 parts by weight of citric acid and 4 ^G -α-glucosyl rutin crystals obtained by the method of Example 2 are added. 1 part by mass of the contained powder and a small amount of lemon flavor were mixed, and then molded and packaged according to a conventional method to obtain a hard candy.

This product is a yellow lemon candy with enhanced vitamin P-like action, low caries and low calories.

<Acetic acid beverage>
10 parts by weight of apple vinegar, 6 parts by weight of rice vinegar, 2 parts by weight of citric acid, 2 parts by weight of malic acid, 38 parts by weight of isomerized sugar, 0.7 parts by weight of enzyme-treated stevia, 1 part by weight of sorbit, 0.5 parts of apple essen Purified water was added to 100 parts by mass of purified water to 0.1 parts by mass of powder, apple fruit juice (1/5 concentrated) 2 parts by mass, and 4 ^G -α-glucosylrutin crystal-containing powder obtained by the method of Example 2. An acetic acid beverage was prepared.

This product is an acetic acid beverage with enhanced vitamin P-like action, and it can be expected that the physiological function of rutin is immediately effective and sustained.

<Orange juice>
Orange fruit juice 50 parts by weight, citric acid 0.1 part by weight, sugar 5 parts by weight, 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2, 0.1 part by weight, L-ascorbic acid (vitamin C ) 0.1 parts by mass, a proper amount of fragrance, and 46 parts by mass of water were mixed, and then the container was filled and sterilized according to a conventional method to obtain an orange juice product.

This product is fortified with vitamin P and vitamin C and contains ^4G -α-glucosylrutin, so the color of orange-derived natural pigments and the flavor of orange are not easily deteriorated, and they are not decomposed by light. It is difficult orange juice.

<Grapefruit jelly>
6 parts by weight of maltitol, 1.2 parts by weight of stabilizer, 1 part by weight of grapefruit sandbag, 0.9 part by weight of pH adjuster, grapefruit juice (1/6 concentrated), 4 ^G obtained by the method of Example 2 A grapefruit jelly was prepared by adding purified water to 0.1 parts by mass of α-glucosylrutin crystal-containing powder, 0.04 parts by mass of enzyme-treated stevia, and 0.01 parts by mass of safflower yellow to make 100 parts by mass as a whole.

This product is a jelly with enhanced vitamin P-like action, and by taking it, it can be expected that the physiological function of rutin is immediately effective and sustained. Further, since it contains 4 ^G -α-glucosyl rutin, it is a jelly in which the flavor of grapefruit juice is prevented from deteriorating.

<Sand cream>
1,200 parts by weight of crystalline maltose, 1,000 parts by weight of shortening, 10 parts by weight of 4 ^G -α-glucosyl rutin crystal-containing powder obtained by the method of Example 2, 1 part by weight of lecithin, 1 part by weight of lemon oil, vanilla 1 part by mass of oil was mixed by a conventional method to produce a sand cream.

This product is a yellow-colored sand cream with enhanced vitamin P-like action, which prevents the oxidation of fats and oils, and has a good mouthfeel, melting condition and flavor.

<Antioxidant>
10 parts by mass of 4 ^G -α-glucosyl rutin crystal-containing powder prepared by the method of Example 2 and 0.2 part by mass of sodium citrate were mixed to obtain an antioxidant.

Since this product has a strong antioxidant action, it can be advantageously used as an antioxidant, stabilizer, anti-fading agent, quality improver and the like. Specifically, oily foods such as margarine and putter cream, anti-sensitive disease agents such as unsaturated fatty acids, oily vitamins and oily hormones, cosmetics such as emulsions and creams, and foods and drinks containing natural pigments that easily fade. The above-mentioned functions are exhibited by mixing them appropriately.

The present invention relates to a novel crystal of 4 ^G -α-glucosyl rutin composed of a ratio of one molecule of 4 ^G -α-glucosyl rutin, one molecule of ethanol and eight molecules of water, the crystal-containing powder, pharmaceutical materials thereof, and cosmetics. The use as a raw material and food material is provided. The 4 ^G -α-glucosyl rutin crystal according to the present invention is itself an effective, safe and stable pharmaceutical material, like rutin, circulatory disease, retinal hemorrhage, gastric weak lung Not only can it be used as a preventive or therapeutic agent for various diseases such as bleeding, hereditary telangiectasia, purpura, allergies, lifestyle-related diseases, but also solubility and stability of 4 ^G -α-glucosylrutin It is also extremely useful as a reagent for elucidating the solid physical properties, the presence or absence of crystal polymorphism, and the transition phenomenon.

In addition, the 4 ^G -α-glucosylrutin crystal-containing powder according to the present invention can be used as a cosmetic material for collagen denaturation inhibitors, sunscreen agents, oral hair restorers, swelling improvers, slimming agents, and the like. Further, as food materials, it can be used as a fading inhibitor, a photodegradation inhibitor, a solubilizing agent for hardly water-soluble substances, an antioxidant for fats and oils, and the like. The present invention greatly opens up the use of 4 ^G -α-glucosyl rutin as a pharmaceutical material, cosmetics, and food material, and its industrial utility is extremely large.

In FIG. 2, a: peak at 7.3 ° (Miller index (hkl): 020) b: peak at 7.6 ° (Miller index: 021) c: peak at 13.1 ° (Miller index: 025) d: Peak at 17.5 ° (Miller index: 008) e: Peak at 18.3 ° (Miller index: 135)

Claims

4 G -α- 4 G -α- glucosyl rutin crystals composed of a ratio of glucosyl rutin 1 molecule of ethanol per molecule and water 8 molecules.
In the powder X-ray diffraction method, the main characteristic diffraction angles (2θ) are 7.3 ° (Miller index (hkl): 020), 7.6 ° (Miller index: 021), 13.1 ° (Miller index: The 4 G -α-glucosyl rutin crystal according to claim 1, which shows 17.5 ° (Miller index: 008) and 18.3 ° (Miller index: 135).
Space group of the crystal is C222 1, the lattice constants a = 8.8337Å unit cell, b = 24.5552Å, a c = 40.3391Å, and, α = β = γ = 90 ° orthorhombic The 4 G -α-glucosyl rutin crystal according to claim 1 or 2, which is an orthohombic system.
4 4 G-.alpha.-glucosyl rutin crystal according to any one of claims 1 to 3 carbon atoms and oxygen atoms have an atomic coordinates shown in the specification in Table 2 to Table 3 constituting the G-.alpha.-glucosyl rutin molecule.
The 4 G -α-glucosyl rutin crystal according to any one of claims 1 to 4, which is in the form of a single crystal.
The 4 G -α-glucosyl rutin crystal-containing powder according to any one of claims 1 to 5.
A pharmaceutical material comprising the 4 G -α-glucosyl rutin crystal according to any one of claims 1 to 5.
A cosmetic or food material containing the 4 G -α-glucosyl rutin crystal-containing powder according to claim 6.
That allowed to crystallize 4 G-.alpha.-glucosyl rutin crystals 4 G-.alpha.-glucosyl rutin crystals from 4 G-.alpha.-glucosyl rutin content solution by using as seed crystals according to any one of claims 1 to 4 A method for producing a 4 G -α-glucosyl rutin crystal-containing powder, which is characterized.