JP6049381B2 - Gnetsum composition containing beekeeping products - Google Patents

Description

  The present invention relates to a composition comprising gnetum having excellent antioxidant action, a processed product thereof or an extract thereof. Furthermore, the present invention provides an antioxidant, a peroxisome proliferator activated receptor (PPAR) α and / or a PPARβ / δ activator, an angiotensin converting enzyme (ACE) inhibitor, a food, a cosmetic, and the like comprising the composition. It relates to a pharmaceutical composition.

  Gnetsum (aka Melinjo, scientific name Gnetum gnemon L., English name Gnemon tree, Indonesian name Melinjo, Belinjo) is a plant belonging to the family Gnetsum and is cultivated in Southeast Asia. In particular, Indonesia has traditionally used gnetsum leaves, flowers, and fruits as food. Gnetsum seeds are crushed and dried, then fried in oil and made into confectionery (emping). As a method of using such a gnetsum, a gnetsum extract extracted from a gnetsum seed, a fermented food of a gnetsum fruit, and the like have been reported (Patent Documents 1 to 7).

  Patent Document 1 describes gnetsum foods using gnetsum seeds, which are safe, have antibacterial action and radical scavenging action, can be eaten with peace of mind, and have a long-lasting life of various processed foods. It is described that improvement is expected.

  Patent Document 2 describes a gnetsum extract characterized by containing a extract obtained by using water and / or an organic solvent of gnetsum seeds as an extractant. The gnetsum extract suppresses lipid oxidation in foods and organisms. It describes that it has effects such as an antioxidant action that protects against oxidative damage and a tyrosinase inhibitory action.

  Moreover, in patent document 2, the main useful components in the aging gnetum extract are gnetin C (gnetin C), gnemonoside A (gnemonoside A), gnemonoside C (gnemonoside C), gnemonoside D (gnemonoside D), These four compounds are all polyphenols belonging to stilbenoids, and the antibacterial action of gnetin C is not pH-dependent from acidic to alkaline, and is neutral, especially not found in other antibacterial substances. It is described that it is characteristic to show also in the area.

  Patent Document 3 describes a fermented food characterized by causing useful microorganisms to act on gnetsum fruit, and the fermented food contains a stilbenoid which is a kind of polyphenol that is safe and has an antibacterial action and a radical scavenging action. Therefore, it is described that the growth of miscellaneous bacteria is suppressed, there is no miscellaneous taste, it is not easy to eat because there is no decrease in flavor due to air oxidation, and prevention of heart disease etc. is expected as a functional food. .

  Patent Document 4 discloses a health drink containing gnetsum-derived stilbenoid as an active ingredient, Patent Document 5 discloses a health maintenance agent containing a gnetsum resveratrol dimer as an active ingredient, and Patent Document 6 discloses Gnetum. An immunostimulant containing an extract as an active ingredient is disclosed in Patent Document 7, and an obesity / diabetes mellitus improving agent containing a gnetsum extract as an active ingredient is described.

  Further, Patent Document 8 describes a novel compound that is isolated from merinjo's internal milk and has an excellent antibacterial action, antioxidant action, and antilipase action.

  On the other hand, beekeeping products are widely used today for health foods, pharmaceuticals, cosmetics, and the like, and various pharmacological and nutritional physiological effects such as vasodilation, blood pressure lowering, and antibacterial action have been reported.

  For example, propolis, a kind of beekeeping product, has been used for people's lives for a long time. In Europe, it is used as an apitherapy (treatment with beekeeping products) along with other beekeeping products such as royal jelly, honey and pollen. It is still used for people's health. Propolis is composed of a wide variety of natural ingredients such as flavonoids, terpenoids, organic acids, amino acids, polysaccharides, minerals, and so far, with antibacterial activity, anti-inflammatory activity, analgesic activity, antipruritic activity, immunostimulatory activity, anti-stimulant activity, It has been reported to have various biological activities such as tumor activity and antioxidant activity (Patent Document 9).

  Similarly, royal jelly, a kind of beekeeping product, contains a good balance of protein, vitamins and minerals, increasing blood flow, lowering blood pressure, promoting growth, sex hormone-like action, lipid-lowering action, antibacterial action, Tumor action, wound healing promoting action, autonomic dysfunction healing action, etc. have been reported (Non-Patent Document 1). There is also a report of anti-stress action (Non-Patent Document 2). Therefore, it is used for quasi-drugs, health foods, cosmetics and the like. In particular, as for the protease-treated product of royal jelly protein, calcium absorption promoting action (Non-patent Document 3) and blood glucose level-lowering action (Non-Patent Document 4) are known, and anti-oxidation action has also been reported (Non-Patent Document). 5) The effect was weaker than vitamin E.

JP 2006-81405 A International Publication No. 2006/030771 JP 2008-22726 A JP 2009-247254 A JP 2009-13123 A JP 2009-44646 A JP 2009-249320 A JP 2010-184886 A JP 2003-55297 A

Akira Fujii, Bee Science, 16 (3), 97 (1995) Ikeda, Yugo et al., Bee Science, 17 (3), 103 (1996) Teruko Nakasa, Food and Development, 34.5 (1999) Shuichiro Ueda, Food Style 21, 6, 5 (2002) Japan Royal Jelly Fair Trade Council "Study on Royal Jelly" 2001 Research Report

  An object of this invention is to provide the composition containing the gnetum which has the outstanding antioxidant effect, its processed material, or those extracts. Furthermore, this invention aims at providing the antioxidant, PPAR (alpha) and / or PPAR (beta) / delta activator, angiotensin converting enzyme inhibitor, foodstuffs, cosmetics, and pharmaceutical composition containing this composition.

  The present inventors have used a beekeeping product such as royal jelly, propolis, pollen load, honey, honey and a gnetsum seed extract in combination, thereby forming an antioxidation by preparing a mixed composition of the beekeeping product and the gnetsum seed extract. The knowledge that power could be improved from the expected value was obtained. Moreover, the knowledge that the said mixed composition can further improve PPAR (alpha) and PPAR (beta) / (delta) agonist activity, and angiotensin converting enzyme inhibitory activity from the expected value was also acquired.

  Based on these findings, the present invention has been completed through further studies. The following composition, an antioxidant containing the composition, PPARα and / or PPARβ / δ activator, angiotensin converting enzyme inhibition An agent, food, cosmetics and pharmaceutical composition are provided.

  Item 1. A composition comprising gnetsum, a processed product thereof or an extract thereof, and a beekeeping product.

  Item 2. Item 2. The composition according to Item 1, wherein the beekeeping product is at least one selected from the group consisting of royal jelly, propolis, pollen load, bee cub, and honey.

  Item 3. Item 3. The composition according to Item 1 or 2, wherein the gnetsum, a processed product thereof, or an extract thereof is a gnetsum seed extract.

  Item 4. Item 4. The composition according to Item 3, wherein the beekeeping product is royal jelly, and 0.1 to 20 parts by weight of the gnetsum seed extract is contained per 1 part by weight of the royal jelly.

  Item 5. Item 4. The composition according to Item 3, wherein the beekeeping product is propolis and contains 0.01 to 20 parts by weight of the gnetsum seed extract with respect to 1 part by weight of the propolis.

  Item 6. Item 4. The composition according to Item 3, wherein the beekeeping product is a pollen product, and 0.01 to 20 parts by weight of the gnetsum seed extract is contained per 1 part by weight of the pollen product.

  Item 7. Item 4. The composition according to Item 3, wherein the beekeeping product is a bee cub and 0.01 to 20 parts by weight of the gnetsum seed extract is added to 1 part by weight of the bee cub.

  Item 8. Item 4. The composition according to Item 3, wherein the beekeeping product is honey, and 0.1 to 20 parts by weight of the gnetsum seed extract per 1 part by weight of the honey.

  Item 9. Item 9. An antioxidant comprising the composition according to any one of Items 1 to 8.

  Item 10. Item 7. A PPARα and / or PPARβ / δ activator comprising the composition according to any one of Items 1 to 3 and 6.

  Item 11. Item 6. An angiotensin converting enzyme inhibitor comprising the composition according to any one of Items 1 to 3 and 5.

  Item 12. Item 10. A food comprising the composition according to any one of Items 1 to 8.

  Item 13. Cosmetics containing the composition in any one of claim | item 1 -8.

  Item 14. Item 9. A pharmaceutical composition comprising the composition according to any one of Items 1 to 8.

  The composition of the present invention has an excellent antioxidant power due to the synergistic effect of gnetsum and beekeeping products. Furthermore, the composition of the present invention has excellent PPARα and / or PPARβ / δ agonist activity and ACE inhibitory activity due to the synergistic effect of gnetsum and beekeeping products. Therefore, the composition of the present invention is useful as a component of foods, cosmetics and pharmaceutical compositions.

  Moreover, since the composition of this invention uses the gnetum conventionally used as a foodstuff material, its safety is high.

FIG. 6 is a graph showing an increase rate (%) of an actual measurement value with respect to an expected value of an ORAC value corresponding to each blending ratio of a royal jelly enzymatic degradation product and a gnetsum seed extract. 3 is a graph showing the rate of increase (%) in measured values with respect to the expected value of ORAC values corresponding to the blending ratios of propolis ethanol extract and gnetsum seed extract. It is a graph which shows the increase rate (%) of the measured value with respect to the expected value of ORAC value corresponding to each compounding ratio of pollen load and gnetsum seed extract. It is a graph which shows the increase rate (%) of the measured value with respect to the expected value of the ORAC value corresponding to each compounding ratio of the bee enzyme degradation product and the gnetsum seed extract. It is a graph which shows the increase rate (%) of the measured value with respect to the expected value of the ORAC value corresponding to each mixing ratio of honey and gnetsum seed extract. FIG. 5 is a graph showing the rate of increase (%) in measured values with respect to the expected value of DPPH radical scavenging activity corresponding to each blending ratio of bee enzyme digest and gnetsum seed extract. 3 is a graph showing the rate of increase (%) in measured values with respect to the expected value of PPARα agonist activity corresponding to each blending ratio of pollen cargo and gnetsum seed extract. 3 is a graph showing the rate of increase (%) in measured values with respect to the expected value of PPARβ / δ agonist activity corresponding to each blending ratio of pollen cargo and gnetsum seed extract. 3 is a graph showing the rate of increase (%) in measured values with respect to the expected value of ACE inhibitory activity corresponding to each blending ratio of propolis ethanol extract and gnetsum seed extract.

  Hereinafter, the present invention will be described in detail.

Gnetum , processed product thereof or extract thereof In the present invention, the site used by gnetum (scientific name Gnetum gnemon L.) is not limited to a part such as a fruit (or seed), a flower or a leaf, but is preferably a seed. The gnetum may be processed, and examples of such processing include drying, heat drying, cutting, and pulverization.

  In the present invention, an extract of gnetum or a processed product thereof can also be used. The extraction method for producing such an extract is not particularly limited, and examples thereof include a method of extraction using a polar solvent and a method of extraction using a supercritical extraction method using carbon dioxide or the like.

  In the present invention, the gnetsum seed is composed of seed coat, thin skin, and embryo / endosperm (inner milk). The shape and form of the gnetsum seed used in the present invention may be any shape or form as long as the effects of the present invention can be obtained, but the major axis: about 1.3 to 2.3 cm, the minor axis : About 0.6 to 1.3 cm, preferably peanut-shaped. The gnetsum seeds can be used in the present invention as long as the gnetsum seeds are contained in the form. For example, the gnetsum seeds may be in the form of a gnetsum fruit having a skin on the gnetsum seeds.

  The gnetsum seeds used in the present invention may be processed, and the processed products of such gnetsum seeds are in an undried raw state, in a dried state (by sun-dried, etc.) Any of the thing of the thing of the thing or the heat-dried state may be sufficient. In addition, the gnetsum seed can be used as a raw material in an original state that has not been cut or crushed, but may be a processed product of sliced or crushed gnetsum seed. In the present invention, it is also possible to use a processed product of gnetsum seed embryo / endosperm (endosperm) or seed coat only.

  In the present invention, it is desirable to use an extract of gnetsum seed, and the extract may be extracted from the gnetsum seed by any method, but preferably by immersing the gnetsum seed in an immersion liquid. It is obtained.

  As the immersion liquid, water, an organic solvent, or a water-containing organic solvent can be used, and the organic solvent is preferably one that is freely miscible with water, such as methanol, ethanol, 1-propanol. , 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, 2-methyl-2-propanol, 1-pentanol, 2-pentanol, 3-pentanol, etc. Lower alcohols, ethers such as diethyl ether, esters such as methyl acetate and ethyl acetate, ketones such as acetone, organic acids such as acetic acid, glacial acetic acid, and propionic acid. The organic solvent is preferably a lower alcohol.

  The temperature of the immersion liquid at the time of immersion can be appropriately set depending on the amount of the gnetsum seed and the immersion liquid, and is, for example, 10 to 50 ° C, preferably 20 to 40 ° C. The time for soaking may be appropriately set depending on the amount of the gnetsum seed and the soaking solution, but is preferably 3 days or more, more preferably 3 to 7 days.

The extract of gnetsum seeds of the present invention can also be obtained by a method comprising the following steps (A) and (B).
(A) a step of immersing gnetsum seeds in an immersion liquid which is water or a water-containing organic solvent, performing solid-liquid separation on the immersion liquid, and collecting a solid matter; and
(B) A step of immersing the solid obtained in the step (A) in an immersion liquid having an organic solvent content of 10 vol% or more higher than the immersion liquid in the step (A), and collecting the immersion liquid.

  The collected immersion liquid can be used as it is, but if necessary, ultrafiltration, molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange chromatography, affinity chromatography, high performance liquid chromatography (HPLC), Purification may be performed by a dialysis method, a combination thereof, or the like.

  The extract of the gnetsum seeds according to the present invention includes a recovered immersion liquid (including those further purified as necessary), a concentrated liquid obtained by concentrating the immersion liquid, or freeze-drying, spray drying, or the like. Any state of the solid from which the solvent has been removed may be used. Here, the concentration of the immersion liquid, lyophilization, and spray drying can be performed according to a conventional method. The form of the seed extract of the present invention is preferably in the form of a powder.

Beekeeping product In the present invention, the beekeeping product means a product obtained by breeding bees, such as honey, royal jelly, propolis, beeswax, bee bread, pollen load, bee pupa. These processed products (such as extract extracts) can be mentioned. In the present invention, royal jelly, propolis, pollen, honey and honey are preferably used.

(Royal Jelly)
Royal jelly (hereinafter also referred to as RJ) is a milky white jelly-like substance made by mixing secretions secreted from the hypopharyngeal gland and the greater vagina by 3 to 12-day-old worker bees. The main physiologically active components in RJ include, for example, organic acids such as 10-hydroxydecenoic acid, which are unique to RJ, and vitamins such as proteins, lipids, saccharides, vitamin Bs, folic acid, nicotinic acid, pantothenic acid, etc. And various minerals.

  The RJ in the present invention includes raw RJ, dried RJ, dried RJ powder, enzymatic degradation products thereof, extracts from organic solvents, fermented products, and the like. The production area of RJ may be any of Japan, China, Brazil, European countries, Oceania countries, the United States, etc.

  The RJ enzyme degradation product can be produced by treating the RJ raw material with at least an enzyme having an endopeptidase action, at least an enzyme having an exopeptidase action, and / or an enzyme having an endopeptidase action and an exopeptidase action.

  Proteolytic enzymes having at least endopeptidase activity include animal origin (eg, trypsin, chymotrypsin, etc.), plant origin (eg, papain, etc.), microorganism origin (eg, lactic acid bacteria, yeast, mold, Bacillus subtilis, actinomycetes, etc.) And endopeptidase.

  Examples of proteolytic enzymes having at least exopeptidase activity include carboxypeptidase, aminopeptidase, microorganism-derived (for example, lactic acid bacteria, Aspergillus spp., Rhizopus spp. Is mentioned.

  Among these various enzymes, those having both exopeptidase activity and endopeptidase activity are preferably Streptomyces griseus-produced peptidase (trade name: actinase AS), Aspergillus oryzae (Aspergillus oryzae). ) Produced peptidase (trade name: Protease A, flavorzyme), Aspergillus melleus produced peptidase (trade name: Protease P), and preferred examples of enzymes having exoprotease activity include Aspergillus oryzae (Aspergillus oryzae) orizae) production peptidase (trade name: Ummamizyme G, Promod 192P, Promod 194P, Sumiteam FLAP), Aspergillus sojae production peptidase (trade name: Sternzyme B15024), Aspergillus genus production peptidase (trade name: Coclase P) And Rhizopus oryzae-producing peptidase (trade name: peptidase R). Further, preferred examples of the enzyme having endoprotease action include Bacillus subtilis producing peptidase (trade name: orientase 22BF, nucleicin), Bacillus licheniformis producing peptidase (trade name: Alcalase) ), Bacillus stearothermophilus produced peptidase (trade name: Protease S), Bacillus amyloliquefaciens produced peptidase (trade name: Neutase), Bacillus genus produced peptidase (trade name) : Protamex).

  Enzyme treatment for reducing RJ allergenicity can be carried out, for example, as described in JP 2007-295919 A and JP 2007-295920 A.

  The organic solvent used for extraction of RJ with an organic solvent is preferably ethanol. The fermented product of RJ can be produced by a conventional method using microorganisms such as yeast and lactic acid bacteria.

(Propolis)
Propolis is a resinous or waxy substance that forms the nest wall of a honeybee's nest. In the present invention, the propolis may be derived from any origin / plant such as Brazil, China, European countries, Oceania, USA, and the like. Accordingly, any propolis such as Aleklin, Super Green, Eucalyptus, and Ultra Green can be used.

  The propolis in the present invention includes, for example, a propolis bulk, a pulverized product thereof, a supercritical extract, an extract with water or a hydrophilic organic solvent, a powder obtained by pulverizing the extract, a granule form obtained by granulating the powder, and the like Is included. Among them, the hydrophilic organic solvent extract is preferable because an active ingredient of propolis is efficiently extracted in a short time in a well-balanced manner, and a large-scale facility is not required for scale-up. As the hydrophilic organic solvent used for extraction, ethanol is preferred.

(Pollen load)
A pollen load is a bee made by bees hardened with nectar, also known as pollen dumpling. The pollen load is stored in the nest along with the honey, and this pollen load can be easily recovered.

  Examples of the plant from which the pollen load is derived in the present invention can include the Brassicaceae, Tadeidae, camelliaceae, Hannichidaceae, Azaleas, Petrelaceae, Gramineae, Willowaceae, Citrus, Cucurbitaceae, Rosaceae, etc. Specific examples include cistus, tea, rapeseed, buckwheat, watermelon, corn, jallah, mari, blueberry, raspberry, apple, pear, cherry, willow, orange, caruna and the like.

  The pollen load in the present invention includes the form of an extract prepared with an appropriate solvent in addition to the form as it is. Here, the pollen load can be extracted with a solvent such as water, a water-containing solvent, or an organic solvent. Moreover, the said extract can also be made into dried products, such as a liquid (concentrated liquid) obtained by concentrating an extract as needed, or a freeze-dried product of the extract, or a spray-dried product.

(Bees)
Bee puppy means bee larvae and pupae. The type of bee is not particularly limited, and a wide range of known bees such as native bees, non-conventional bees such as western bees, African bees, hornets (including cross-bees), wasps, bumblebees, etc. are widely used. be able to. A bee other than a native species or a native species is preferable, and a western bee is more preferable because of availability. It should be noted that males and females may be distinguished, but males are preferable.

  Larva and pupae are not particularly limited as long as they are hatched from eggs, but preferably bee larvae and pupae that have passed 16 to 23 days after hatching, more preferably bee larvae and pupae that have passed 18 to 21 days after hatching. Is used.

  In the present invention, a bee is used in a state in which a raw bee and a raw bee are processed. As processed products of bees, concretely, pulverized bees (raw or dried), dried bees (raw or crushed), and bees (raw, dried) Or a product obtained by heat-treating a pulverized product), or a product obtained by extracting a honey bean with water, hydrous ethanol or the like. Preferably, a dried powder of honey mushroom prepared by pulverizing after drying a bee (raw) can be mentioned.

  The term `` bee '' in the present invention, unless otherwise specified, in addition to a raw bee, a processed product obtained by subjecting the bee to drying, pulverization, or heating, a bee ( (Including raw, dried and pulverized products) extracted with water or water-containing ethanol, and those obtained by treating bees and processed products with proteolytic enzymes (peptidases).

  The bees and their processed products are treated with proteolytic enzymes to reduce the molecular weight of the protein contained in the bees and their processed products, so that allergic reactions caused by the proteins are suppressed ( It is expected that a product with reduced allergenase will be obtained.

  Peptidases can be preferably used as the proteolytic enzymes used for enzyme treatment of bees and processed products thereof. Specific examples of peptidases include those described in the above item “Royal Jelly”. .

(honey)
Honey is a natural sweetener that bees make from nectar collected from flowers and store it in their nests. Depending on the type of flower, honey is also classified into astragalus honey, clover honey, acacia honey, and the like, but any honey can be used in the present invention without any particular limitation. Two or more kinds of honey can be mixed and used.

Composition The composition of the present invention is characterized in that it contains gnetum, a processed product thereof or an extract thereof (hereinafter also referred to as gnetum or the like), and a beekeeping product.

  Thus, the combined use of gnetsum or the like and a beekeeping product can improve the antioxidant power by a synergistic effect. Furthermore, PPARα and / or PPARβ / δ agonist activity and ACE inhibitory activity can be improved by a synergistic effect.

  The ratio of the gnetum and the like and the beekeeping product contained in the composition of the present invention is not particularly limited as long as the effect of the present invention is obtained, but can be appropriately adjusted according to the final form and the like. Can be appropriately selected from the range of 0.01 to 100% by weight.

The ratio of gnetum and the like to the beekeeping product in the composition of the present invention is not particularly limited as long as the effect of the present invention is obtained, and can be set as appropriate. Describe.
The amount of gnetsum seed extract is preferably 0.1 to 20 parts by weight, more preferably 0.1 to 10 parts by weight, and still more preferably 0.1 to 1 part by weight with respect to 1 part by weight of royal jelly. Here, the royal jelly is preferably a royal jelly enzymatic degradation product.
The amount of the gnetsum seed extract is preferably 0.01 to 20 parts by weight, more preferably 0.01 to 1 part by weight, and still more preferably 0.1 to 1 part by weight with respect to 1 part by weight of propolis. Here, the propolis is preferably a propolis extract.
-The amount of gnetsum seed extract is preferably 0.01 to 20 parts by weight, more preferably 0.01 to 1, 10 to 20 parts by weight, and still more preferably 0.01 to 1 part by weight with respect to 1 part by weight of pollen.
The amount of the gnetsum seed extract is preferably 0.01 to 20 parts by weight, more preferably 0.01 to 0.2 parts by weight, and still more preferably 0.01 to 0.1 parts by weight with respect to 1 part by weight of the bee. Here, the bees are preferably bee enzyme degradation products.
The amount of the gnetsum seed extract is preferably 0.1 to 20 parts by weight, more preferably 0.1 to 2 parts by weight, and still more preferably 0.5 to 1 part by weight with respect to 1 part by weight of honey.

  In the composition of the present invention, known components other than those described above can be appropriately blended within a range not impeding the effects of the present invention.

Antioxidant The antioxidant of the present invention is characterized by containing a composition containing gnetsum, a processed product thereof or an extract thereof, and a beekeeping product.

  Since the composition of the present invention has an antioxidant action, it can be suitably used as an antioxidant.

  The antioxidant of the present invention can be suitably used, for example, in the fields of foods, cosmetics, pharmaceuticals, and the like, and by blending with these, it is possible to prevent product oxidation and suppress quality deterioration. The antioxidant of the present invention can have any form depending on the shape of the target product. Moreover, another component can be mix | blended suitably as needed.

  The content of the gnetum and the beekeeping product contained in the antioxidant of the present invention is not particularly limited because the final content when contained in foods, cosmetics, pharmaceuticals, etc. is important, but the total amount is 0.01 to It is possible to appropriately select from the range of 100% by weight.

PPARα and / or PPARβ / δ activator The PPARα and / or PPARβ / δ activator of the present invention comprises a composition containing gnetsum, a processed product thereof or an extract thereof, and a beekeeping product. To do. As a beekeeping product, a pollen load can be preferably used.

  Since the composition of the present invention has PPARα and / or PPARβ / δ agonist activity, it can be suitably used as a PPARα and / or PPARβ / δ activator.

  The PPARα and / or PPARβ / δ activator of the present invention can be suitably used in the fields of foods, cosmetics, pharmaceuticals and the like. The PPARα and / or PPARβ / δ activator of the present invention can have any form depending on the shape of the target product. Moreover, another component can be mix | blended suitably as needed.

  The content of gnetum, etc. and beekeeping products contained in the PPARα and / or PPARβ / δ activator of the present invention is particularly limited because the final content when contained in foods, cosmetics, pharmaceuticals, etc. is important. However, the total amount can be appropriately selected from the range of 0.01 to 100% by weight.

Angiotensin converting enzyme inhibitor The angiotensin converting enzyme inhibitor of the present invention is characterized by containing a composition containing gnetsum, a processed product thereof or an extract thereof, and a beekeeping product. Propolis can be suitably used as the beekeeping product.

  Since the composition of the present invention has ACE inhibitory activity, it can be suitably used as an angiotensin converting enzyme inhibitor.

  The angiotensin converting enzyme inhibitor of the present invention can be suitably used, for example, in the fields of food, medicine and the like. The angiotensin converting enzyme inhibitor of the present invention can have any form depending on the shape of the target product. Moreover, another component can be mix | blended suitably as needed.

  The content of the gnetum and the beekeeping product contained in the angiotensin converting enzyme inhibitor of the present invention is not particularly limited because the final content when contained in foods, pharmaceuticals and the like is important, but the total amount is 0.01 to 100 It is possible to select appropriately from the range of wt%.

Foodstuff The foodstuff of this invention contains the composition containing gnetsum, its processed material, or those extracts, and beekeeping products.

  Since the food of the present invention has an antioxidant action, it can improve and / or prevent diseases or symptoms caused by active oxygen, unsaturated fatty acid oxides, lipid peroxides, etc., and The gut microbiota can be improved by inhibiting fat absorption and inhibiting the growth of harmful gut bacteria. Furthermore, since the food of the present invention has PPARα and / or PPARβ / δ activation action and ACE inhibitory action, it activates fatty acid metabolism, prevents and / or improves dyslipidemia, prevents and / or improves obesity, Hypertension can be prevented and / or ameliorated, and arteriosclerosis prevented and / or ameliorated.

  Food includes all foods that animals (including humans) can consume.

  The contents of the gnetsum and the beekeeping product contained in the food of the present invention can be appropriately selected from the range of 0.01 to 100% by weight in total.

  In the food of the present invention, as necessary, minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, Colorants, fragrances, stabilizers, preservatives, sustained release regulators, surfactants, solubilizers, wetting agents and the like can be blended.

  The type of the food of the present invention is not particularly limited. For example, beverages (soft drinks such as coffee, juice, tea drinks, milk drinks, lactic acid bacteria drinks, yogurt drinks, carbonated drinks, sake, western liquor, fruit seeds, honey Liquors such as sake); Spreads (such as custard cream); Pastes (such as fruit paste); Pastry (chocolate, donut, pie, cream puff, gum, jelly, candy, cookies, cakes, pudding, etc.); Japanese confectionery Kinds (Daifuku, salmon, buns, castella, anmitsu, mutton, etc.); Ice confectionery (ice cream, popsicle, sherbet, etc.); , Honey, propolis, etc.); seasonings (dressing, sprinkles, umami seasonings, soup ingredients, etc.).

  Further, the food of the present invention improves and / or prevents diseases or symptoms caused by active oxygen, unsaturated fatty acid oxides, lipid peroxides, etc., suppresses fat absorption, and is harmful. Suppresses the growth of intestinal bacteria, improves intestinal flora, activates fatty acid metabolism, prevents and / or improves dyslipidemia, prevents and / or improves obesity, prevents hypertension and / or Or it can be used as a health food, functional food, dietary supplement, supplement, or food for specified health use that can be improved and prevented and / or improved atherosclerosis. The dosage unit form for use as a supplement is not particularly limited and may be appropriately selected. Examples thereof include tablets, capsules, granules, liquids, and powders.

  The production method of the food of the present invention is not particularly limited, and can be appropriately followed by a known method. For example, the above-mentioned gnetsum and beekeeping products can be mixed or sprayed with the intermediate product or the final product in the food production process as described above to obtain a food used for the above purpose.

Cosmetics The cosmetics of the present invention are characterized by containing a composition containing the above gnetsum, a processed product thereof or an extract thereof, and a beekeeping product.

  Since the cosmetic of the present invention has an antioxidant action, it whitens the skin and prevents skin aging, and thus is useful as a whitening cosmetic, an anti-aging cosmetic (anti-aging cosmetic), and the like. Furthermore, since the cosmetic of the present invention has a PPARα and / or PPARβ / δ activation action, it can improve skin barrier function by maturation of epidermal barrier, activation and differentiation of sebocytes, pre-differentiation of keratinocytes, etc. .

  The cosmetics of the present invention include all cosmetics applied to the skin, mucous membranes, body hair, head hair, scalp, nails, teeth, face skin, lips, etc. of animals (including humans).

  The contents of gnetsum and the like and the beekeeping product in the cosmetic of the present invention can be appropriately selected from the range of 0.0001 to 60% by weight in the total amount of the cosmetic.

  In the cosmetics of the present invention, in addition to gnetsum and beekeeping products, components usually used in cosmetics, such as whitening agents, moisturizers, antioxidants, oily components, ultraviolet absorbers, surfactants, thickeners, Alcohols, powder components, color materials, aqueous components, water, various skin nutrients, and the like can be appropriately blended as necessary.

  The cosmetic dosage form of the present invention includes an aqueous solution system, a solubilization system, an emulsification system, a powder system, an oil liquid system, a gel system, an ointment system, an aerosol system, a water-oil two-layer system, and a water-oil-powder three-layer system. A wide range of dosage forms can be adopted.

  The use of the cosmetics of the present invention is also optional. For example, if it is a basic cosmetic, examples include face wash, lotion, milky lotion, cream, gel, essence, cosmetic liquid, pack, mask, etc. , Foundation, lipstick, blusher, eye shadow, eyeliner, mascara, etc., nail cosmetics include nail polish, base coat, top coat, remover, etc. Examples include cleansing agents, after-shave lotions, pre-shave lotions, shaving creams, body soaps, soaps, shampoos, rinses, hair treatments, hair styling agents, hair styling agents, hair restorers, antiperspirants, and bathing agents.

Pharmaceutical composition The pharmaceutical composition of the present invention is characterized by containing a composition comprising gnetsum, a processed product thereof or an extract thereof, and a beekeeping product.

  Since the pharmaceutical composition of the present invention has an antioxidant action, it can improve and / or prevent diseases or symptoms caused by active oxygen, unsaturated fatty acid oxides, lipid peroxides, and the like. . Furthermore, since the pharmaceutical composition of the present invention has PPARα and / or PPARβ / δ activation action and ACE inhibitory action, it activates fatty acid metabolism, prevents and / or improves dyslipidemia, prevents obesity and / or Or may improve, prevent and / or improve hypertension, and prevent and / or improve arteriosclerosis.

  When preparing as a pharmaceutical composition, Gnetsum etc. and beekeeping products together with non-toxic carriers, diluents or excipients acceptable in pharmaceuticals, tablets (plain tablets, dragees, effervescent tablets, film-coated tablets, chewable tablets, (Including lozenges), capsules, pills, powders (powder), fine granules, granules, solutions, suspensions, emulsions, syrups, pastes, etc. It can be made into a formulation.

  The contents of gnetsum and the like and the beekeeping product contained in the pharmaceutical composition of the present invention can be appropriately selected from the range of 0.01 to 100% by weight in total.

  The amount of intake of the composition of the present invention can be appropriately selected according to the age, weight, symptom, etc. of the intake person or intake animal.

  Examples are given below to illustrate the present invention in more detail. However, the present invention is not limited to these examples.

[material]
In the following test examples and formulation examples, the following were used.

Gnetsum Seed Extract As a gnetsum seed extract powder, a raw material (Lot YMP-M-100109) manufactured by Yamada Apiary Co., Ltd. was used.

According to Example 1 of Patent No. 3994120 of a royal jelly enzymatic degradation product, a royal jelly enzymatic degradation product was prepared.

Preparation of Propolis Ethanol Extract Extract A proline ethanol extract was prepared by concentrating the ethanol extract of Alecrin propolis bulk (from Minas Gerais State) to a solid content of 55%.

Pollen-loaded Mali pollen-loaded from Australia was crushed in a mortar.

Enzymatic degradation product of bees was obtained in accordance with Experimental Example 2 <Preparation of Sample> of JP 2009-159997 A, using actinase AS as an enzyme.

Honey Romanian acacia honey was used.

[Test Example 1]
Antioxidant power measurement test The ORAC method was used to measure the antioxidant power. The test samples used were gnetsum seed extract, royal jelly enzyme digest, propolis ethanol extract, pollen load, bee enzyme digest, and honey. The supernatant obtained by adding 1,000 parts by weight of 50% ethanol aqueous solution to 1 part by weight of the test sample, stirring, and removing the precipitate by centrifugation was used. Each test sample was used alone or after each test sample was mixed at a predetermined blending ratio, a dilution series was prepared with a phosphate buffer and used in the antioxidant activity measurement test (ORAC method).

Inject 96 μl of blank (phosphate buffer only), Trolox ((±) -6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid / standard) and 20 μl sample into 96-well plate did. Then, 200 μl of 94.4 nmol / L fluorescein solution (FL solution) was dispensed into each well, and the fluorescence intensity was measured. Furthermore, 75 μL of 17.2 mg / mL AAPH (2,2′-Azobis (2-amidinopropane) dihydrochloride) solution was added, and the change in fluorescence intensity with time was measured. Based on the obtained fluorescence intensity value, an ORAC value was calculated and used as an actual measurement value. The ORAC value was calculated according to the report ¹⁾ of XIANLI WU et al.

  In addition, the expected value was calculated from the ORAC value obtained when each sample was used alone by the following formula.

Expected value =
(ORA value of A) × (A blending ratio) / {(B blending ratio) + (A blending ratio)}
+ (ORA value of B) × (B blending ratio) / {(B blending ratio) + (A blending ratio)}
(Here, A indicates a gnetsum seed extract, and B indicates other samples.)

  Tables 1 to 5 show expected values, measured values, and rate of increase in measured values (%) with respect to the expected values for each mixture ratio of the sample of the gnetsum seed extract and each of the beekeeping products. The increase rate (%) of the actual measurement value with respect to the value is shown in FIGS.

これらの結果から、グネツム種子の抽出物と各養蜂産品の混合物について抗酸化力を示すORAC値は、実測値が期待値よりも高くなっていた。このことから、グネツム種子の抽出物と各養蜂産品を組み合わせることによって、相乗効果が得られることが分かった。
1) XIANLI WU et al., “Lipophilic and Hydrophilic Antioxidant Capacities of Common Foods in the United States,” J. Agric. Food Chem. 2004, 52, 4026-403

From these results, the actual value of the ORAC value indicating the antioxidant power of the mixture of the gnetsum seed extract and each beekeeping product was higher than the expected value. From this, it was found that a synergistic effect was obtained by combining the extract of gnetsum seeds and each beekeeping product.
1) XIANLI WU et al., “Lipophilic and Hydrophilic Antioxidant Capacities of Common Foods in the United States,” J. Agric. Food Chem. 2004, 52, 4026-403

[Test Example 2]
Antioxidant power measurement test DPPH method was used to measure antioxidant power. The test samples used were an extract of gnetsum seeds and an enzyme degradation product of bees. A 50% ethanol aqueous solution corresponding to 1,000 parts by weight with respect to 10 parts by weight of the test sample was added and stirred. A test sample prepared in a dilution series with a 50% aqueous ethanol solution or a mixture of them in a predetermined blending ratio was used for the antioxidant power measurement test (DPPH method).

  50 μl of 200 mM MES buffer solution and 50 μl of 800 μM DPPH solution were added to and mixed with 100 μl of the control (50% EtOH only) and each test sample, reacted at room temperature for 20 minutes, and the absorbance at 540 nm was measured. The absorbance at 540 nm was measured in the same manner for a mixture of 50% ethanol aqueous solution (for color correction) instead of DPPH solution. DPPH radical scavenging activity was determined from the following formula.

DPPH radical scavenging activity (%) = {(Ac−As) / Ac} × 100
Ac: absorbance at 540 nm of control As: (absorbance at 540 nm of DPPH ethanol sample solution)-(absorbance at 540 nm of sample solution for color correction)

  In addition, the expected value was calculated as the sum of actual values obtained by testing independently at the final concentration of each component in the formulation.

  Table 6 shows the expected value, actual value, and rate of increase (%) of the actual value with respect to the expected value for each mixture ratio of the sample of the gnetsum seed extract and each sample of the bees. The increase rate (%) of the value is shown in FIG.

表６に示されるように、グネツム種子の抽出物と蜂の子の混合物のDPPHラジカル消去能は、期待値よりも高くなっていた。このことから、グネツム種子の抽出物と蜂の子を組み合わせることによって、ラジカル消去能が高まることが明らかになった。

As shown in Table 6, the DPPH radical scavenging ability of the mixture of gnetsum seed extract and bee pup was higher than expected. From this, it was clarified that the radical scavenging ability is enhanced by combining the extract of gnetsum seeds with bees.

[Test Example 3]
PPARs agonist activity measurement test
A reporter gene assay system using cultured animal cells (COS-1 cells) was used to evaluate PPARs agonist activity. The test samples used were gnetsum seed extract and pollen load. As the test sample, DMSO was added and stirred. The test samples were prepared in dilution series with DMSO, and each was used alone, or each test sample was mixed at a predetermined blending ratio and used for a PPARs agonist activity measurement test.

COS-1 cells were cultured using Dulbecco's modified MEM medium containing 10% fetal bovine serum in the presence of 5% CO _{2 at} 37 ° C.

The COS-1 cells were transfected with 3 types of plasmids (pPPARα and δ-Gal, pGal4-Luc and pSEAP-control) and used for PPARα and PPARβ / δ activation tests. Transfected COS-1 cells were collected, seeded in 96-well microplates at 0.6 × 10 ⁴ cells / well (125 μl / well), added with 1.25 μl of the test solution, and cultured for 24 hours. 25 μl of the culture solution was collected in another 96-well microplate, and secreted alkaline phosphatase activity was measured. Also, 100 μl of luciferase activity measurement solution (60 mM Tricine pH7.8, 16 mM basic MgCO ₃ , 0.4 mM EDTA, 1% Triton X-100, 0.5 mM luciferin, 1.5 mM ATP, 0.5 mM CoA, 0.1 mM β -mercaptoethanol) was added and incubated in a dark room for a certain period of time, and then the luminescence intensity was measured. In the activity evaluation, luciferase activity was corrected with secretory alkaline phosphatase activity. As positive controls for PPARa and PPARβ / δ, 0.5 mM Wy14643 and 10 nM GW0742 were used, respectively, and the activities of the samples were compared when the positive control activity was 1.

  PPARs agonist activity was determined from the following equation. The results are shown in Tables 7 and 8.

PPARs agonist activity (%) = (As−Ab) / (Ac−Ab)
Ac: Activity of positive control (Wy14643 or GW0742) Ab: Activity of DMSO As: Activity of sample

  In addition, the expected value was calculated as the sum of actual values obtained by testing independently at the final concentration of each component in the formulation.

  Tables 7 and 8 show the expected value, actual value, and the rate of increase of the actual value relative to the expected value (%) in Tables 7 and 8 for the mixture of the sample of gnetsum seed extract and each sample of pollen cargo. 7 and 8.

表７及び表８に示されるように、グネツム種子の抽出物と花粉荷の混合物のPPARα及びPPARβ/δアゴニスト活性は、期待値よりも高くなっていた。このことから、グネツム種子の抽出物と花粉荷を組み合わせることによって、PPARα及びPPARβ/δアゴニスト活性が高まることが明らかになった。

As shown in Tables 7 and 8, the PPARα and PPARβ / δ agonist activities of the mixture of the gnetsum seed extract and the pollen load were higher than expected. From this, it became clear that the PPARα and PPARβ / δ agonist activities are enhanced by combining the extract of gnetsum seeds and pollen load.

[Test Example 4]
ACE inhibition test
For the ACE inhibitory activity test, ACE Kit-WST (ACE inhibitory activity measurement kit, manufactured by Dojindo Laboratories) was used. The test samples used were an extract of gnetsum seeds and a propolis ethanol extract. The test sample used was DMSO added and stirred. The test samples were prepared in dilution series with DMSO, and each was used alone, or each test sample was mixed at a predetermined blending ratio and used for the ACE inhibitory activity measurement test.

  The test was conducted according to the method of using the kit. That is, 20 μl of ACE and aminoacylase mixture prepared in ultrapure water in each well of a 96-well microplate, substrate solution (3-Hydroxybutyl-Gly-Gly-Gly, (3) HB-GGG) 20 μl, sample dilution 20 μl Were mixed and reacted at 37 ° C. for 1 hour. To this, 200 μl of a mixed solution of 3-hydroxybutyrate dehydrogenase and coenzyme was added and allowed to react at room temperature for 10 minutes. After the reaction, absorbance at 450 nm was measured, and the inhibition rate was calculated based on the obtained data. The inhibition rate was calculated by the following formula described in the instruction manual of the kit.

Inhibition rate = [(Ac-As) / (Ac-Ab)] × 100
Ac: Absorbance at 540 nm of control (no ACE inhibition)
Ab: Absorbance of reagent blank at 540 nm (no ACE activity)
As: Absorbance of the sample at 540 nm

  In addition, the expected value was calculated as the sum of actual values obtained by testing independently at the final concentration of each component in the formulation.

  Table 9 shows the expected value at each blending ratio, the actual measurement value, and the increase rate (%) of the actual measurement value with respect to the expected value for the mixture of the sample of gnetsum seed extract and each sample of propolis ethanol extract. The increase rate (%) of the actually measured value is shown in FIG.

表９に示されるように、グネツム種子の抽出物とプロポリスエタノール抽出エキスの混合物のACE阻害活性は、期待値よりも高くなっていた。このことから、グネツム種子の抽出物とプロポリスエタノール抽出エキスを組み合わせることによって、高血圧予防及び改善効果が高まることが明らかになった。

As shown in Table 9, the ACE inhibitory activity of the mixture of the gnetsum seed extract and the propolis ethanol extract was higher than expected. From this, it was clarified that the effect of preventing and improving hypertension is enhanced by combining the extract of gnetsum seed and the extract of propolis ethanol.

[Prescription example]
Hereinafter, formulation examples of foods, cosmetics and pharmaceutical compositions of the present invention will be shown.

Formulation Example 1 Tablet gnetsum seed extract powder 30 mg, royal jelly enzyme degradation product 5 mg, sucrose fatty acid ester 3 mg, crystalline cellulose 120 mg and dextrin 250 mg were mixed and compressed to obtain tablets.

Formulation Example 2 Capsules Gnetsum seed extract powder 20 mg, propolis ethanol extract 50 mg, sucrose fatty acid ester 4 mg and dextrin 180 mg were mixed and filled into a capsule to obtain a capsule preparation.

Formulation Example 3 Tablet gnetsum seed extract powder 60 mg, Australian mari pollen 3 mg, sucrose fatty acid ester 3 mg, crystalline cellulose 100 mg and dextrin 210 mg were mixed and compressed to obtain tablets.

Formulation Example 4 Tablet gnetsum seed extract powder 75 mg, bee enzyme degradation product 4 mg, sucrose fatty acid ester 4 mg, crystalline cellulose 115 mg and dextrin 197 mg were mixed and tableted to obtain tablets.

Formulation Example 5 Capsules Gnetsum seed extract powder 55 mg, Romanian acacia honey 20 mg, sucrose fatty acid ester 5 mg and dextrin 220 mg were mixed and filled into a capsule to obtain a capsule preparation.

Formulation Example 6 Lotion Toner lotion was prepared according to a conventional method using each component shown in Table 10 below. However, the beekeeping product extract is prepared by extracting royal jelly, propolis, pollen cargo or bee buds with 50% aqueous ethanol, removing ethanol by concentration under reduced pressure, and adding equal amounts of 1,3-butylene glycol and purified water to add solid content. Was prepared to 2%.

Formulation Example 7 Emulsion An emulsion was prepared according to a conventional method using each component displayed in Table 11 below.

Claims (7)

A composition comprising a gnetsum seed extract and a beekeeping product ,
The beekeeping product is royal jelly, propolis, pollen load, bee or honey;
When the beekeeping product is royal jelly, 0.1-1 part by weight of the gnetsum seed extract is included with respect to 1 part by weight of the royal jelly,
When the beekeeping product is propolis, 0.1-1 part by weight of the gnetsum seed extract is included with respect to 1 part by weight of the propolis,
When the beekeeping product is a pollen load, 10 to 20 parts by weight of the gnetsum seed extract with respect to 1 part by weight of the pollen load,
When the beekeeping product is a bee, 0.01 to 0.1 parts by weight of the gnetsum seed extract with respect to 1 part by weight of the bee,
When the beekeeping product is honey, 0.1 to 2 parts by weight of the gnetsum seed extract per 1 part by weight of the honey,
Composition . A composition comprising gnetsum seed extract and pollen load,
0.01 to 1 part by weight of the gnetsum seed extract per 1 part by weight of the pollen load,
Composition. An antioxidant comprising the composition of claim 1 . A PPARα and / or PPARβ / δ activator comprising the composition according to claim 2 . A food comprising the composition according to claim 1 or 2 . Cosmetics containing the composition of Claim 1 or 2 . A pharmaceutical composition comprising the composition according to claim 1 or 2 .

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