JP2008280271A - Agent for preventing photoaging of skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin aging prevention agent containing a new component, a food produced by using the agent, a drug for mammals including human, an external preparation for skin and a feed for mammals. <P>SOLUTION: The agent for preventing the photoaging of skin contains an extract of a plant belonging to the family Cistanche as an active component. Preferable embodiments of the invention comprises the use of a phenylethanoid glycoside as an active component, the use of at least one substance selected from echinacoside and acteoside as the phenylethanoid glycoside and the use of both of echinacoside and acteoside as the active components. The agent for preventing photoaging of skin can be used as drugs for mammals including human, external preparations for skin, foods and drinks and feeds for mammals. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a skin photoaging preventive agent using a novel component. The present invention is widely used for medicines for mammals including humans, external preparations for skin, foods and the like.

Conventionally, it has been known that fresh stalks of herbs belonging to the family Cistanche are effective in treating infertility, impotence, constipation, and the like (see Patent Document 1). In addition, preparations obtained from fresh perennial herb stems provide blood and kidney nutrition. These parasites and perennial herbs are widely cultivated in the northwestern region of China and are known in some regions as “desert ginseng”. The species of Cistanche, the most cultivated species, is the all parasitic plant [Cistanche]
tubulosa].

  Japanese scientists have systematically studied the chemical constituents and pharmacological activities of Cistanche, and found that phenylethanoid glycosides are the main active ingredients in these perennial herbs (eg, Non-patent documents 1 to 3). Such active ingredients are effective antioxidants, metabolism promoters, memory promoters, libido promoters and the like. The medical properties of various phenylethanoid glycoside compounds have been studied by many researchers.

JP 2004-250449 A SatoT., Et al. Yakugaku Zasshi, 1985, 105 (12): 1131 JimenezC., Et al. Nat Prod Rep, 1994, 11 (6): 591 CometaF., Et al. Fitoterapia, 1993, 64 (3): 195 DengMin et al. Acta Pharmacoe Sin, 2004, 25 (10) 1276-1284

On the other hand, skin aging generally refers to a physiological phenomenon that occurs when physiological aging associated with aging and photoaging due to sunlight exposure (ultraviolet rays) interact with each other. The relationship with wrinkles, rough skin, pigmentation such as spots and freckles (Gilchrest; Photodamage: Blackwell)
Science, Inc. , 1995). In other words, it is known that long-term exposure to the sun (ultraviolet rays) increases deep wrinkles on the face and neck, and also causes skin dryness and skin pigmentation such as rough skin, freckles, and freckles. Troubles in the world became a problem.

Conventionally, cosmetics containing various UV absorbing, scattering and shielding materials such as titanium oxide, zinc oxide, paramethoxycinnamic acid ester and paraaminobenzoic acid ester in order to prevent the acceleration of photoaging in the skin due to these ultraviolet rays ( Sunscreen and sun protect cosmetics) have been developed and used. However, even if these cosmetics are used, it is difficult to protect the skin from overwhelming sun exposure. In addition, as a method for improving the photoaging symptoms of the skin, it is widely known that an external application of all-trans retinoic acid is effective (by Gilchrest; Photodamage: Blackwell).
Science, Inc. , 1995, etc.), which is limited to use by doctors in Japan due to cosmetic science problems such as skin irritation and safety problems, and is highly effective and highly safe. The development of an anti-aging agent and an external preparation for skin was eagerly desired.

Under such circumstances, ingestion of echinacoside and acteoside and plants belonging to Cistanche containing them into photoaging mice (irradiating hairless mice with ultraviolet rays), effects on wrinkle formation and skin aging-related As a result of evaluating the influence on genes (hyaluronidase, collagenase), it was found that echinacoside and acteoside and plants belonging to Cistanche containing them have a skin photoaging preventive action, and the present invention was completed.
That is, an object of the present invention is to provide a novel anti-skin aging preventive agent and a food product using the same, a pharmaceutical product for mammals including humans and an external preparation for skin, and a feed for mammalian animals.

In order to solve the above problems, the present invention has the following characteristics.
1. A skin photoaging preventive agent comprising a phenylethanoid glycoside as an active ingredient.
2. The phenylethanoid glycoside includes at least one of echinacoside and acteoside. The skin photoaging preventive agent according to 1.
3. 2. The phenylethanoid glycoside includes echinacoside and acteoside. The skin photoaging preventive agent according to 1.
4). An agent for preventing skin photoaging, comprising an extract of a plant of the genus Crestaceae as an active ingredient.
5. 3. The extract according to the above item 4, wherein the extract contains phenylethanoid glycoside as an active ingredient. The skin photoaging preventive agent according to 1.
6). 4. The extract as described above, wherein the phenylethanoid glycoside contains at least one of echinacoside and acteoside. The skin photoaging preventive agent according to 1.
7). 5. The extract according to the above item 6, wherein the extract contains echinacoside and acteoside as the phenylethanoid glycoside. The skin photoaging preventive agent according to 1.
8). Above 1. To 7. above. A pharmaceutical product for mammals, including humans, comprising the skin photoaging preventive agent according to any one of the above as an active ingredient.
9. Above 1. To 7. above. A skin external preparation for mammals including humans, comprising the skin photoaging preventive agent according to any one of the above as an active ingredient.
10. Above 1. To 7. above. A food or drink comprising the skin photoaging preventive agent according to any one of the above as an active ingredient.
11. Above 1. To 7. above. A mammal animal feed comprising the skin photoaging preventive agent according to any one of the above items as an active ingredient.

Hereinafter, the present invention will be described in detail.
The skin photoaging preventive agent of the present invention comprises phenylethanoid glycoside as an active ingredient.

Here, the above “phenylethanoid glycoside” refers to a compound represented by the following chemical formula (1).

  The phenylethanoid glycoside is not particularly limited. For example, echinacoside, acteoside, 2′-acetylacetoside; campneoside I; campneoside II; (cistantubuloside) A, B1, B2, C1, C2; crenatoside; decaffeoylacteoside; isoacteoside; rhodioloside; syringalide A; 3 ' -Α-L-rhamnopyranoside, tubuloside A and the like. These may be used alone or in combination of two or more.

  The skin photoaging preventive agent preferably contains at least one of echinacoside and acteoside as a phenylethanoid glycoside, and further contains both echinacoside and acteoside. It is because it has a higher skin photoaging prevention effect.

The method for obtaining the phenylethanoid glycoside is not particularly limited, and may be obtained by synthesis or may be obtained by extraction from a plant.
Moreover, when extracting from a plant, the plant used as a raw material is not specifically limited, For example, the ground medicine which is a crude drug, the rhododendron plant chorogi, the pepper family pepper genus, the olive fruit, the herbaceous plant herbaceous plant etc. are mentioned. These may be used alone or in combination of two or more. Of these, it is most preferable to use plants of the family Amaranthaceae. In addition to echinacoside and acteoside as phenylethanoid glycosides, 2'-acetylacteoside; campneoside I; campneoside II; cistantubuloside A, B1, B2, C1, C2 Decaffeoylacteoside; isoacteoside; rhodioloside; syringalide A; 3′-α-L-rhamnopyranoside, tubuloside A, etc. This is because it contains a higher skin photoaging preventive effect.
Here, the plant of the Amaranthaceae used as a raw material is not specifically limited, For example, all parasitic plants [Cistanche tubulosa: Kankaniku Juyou], Hononiku (Cistanche salsa: Nikujuyou), Namban Giselle (Aeginetia)
indica) and Onyk (Boschniakia rossica), but are not limited thereto. These may be used alone or in combination of two or more. Of these, the whole parasitic plant [Cistanche tubulosa: kankanikujuyou] is particularly preferable.

  The relationship between the above-described components of the phenylethanoid glycoside and the chemical formula (1) is shown below. However, the structural formula of crenatoside is shown in the following chemical formula (2). Among the above components, most of the components other than echinacoside and acteoside are contained in a small amount or a trace amount in the preparation.

All the compounds shown in Table 1 can be confirmed by high performance liquid chromatography (HPLC). Under the present circumstances, the conditions of high performance liquid chromatography are as follows. The stationary phase is C18 alkylsilane silicone, the mobile phase is acetonitrile-0.05M phosphoric acid aqueous solution (elution gradient 4: 96 → 15: 85), the flow rate is 1 ml / min, and the detection wavelength is 330 nm. It is.

  The other skin photoaging preventive agent of the present invention is characterized by containing an extract extracted from a plant of the family Amaranthaceae as an active ingredient.

Here, the plant of the Amaranthaceae used as a raw material is not specifically limited, For example, all parasitic plants [Cistanche tubulosa: Kankaniku Juyou], Hononiku (Cistanche salsa: Nikujuyou), Namban Giselle (Aeginetia)
indica) and Onyk (scientific name: Boschniakia rossica), but are not limited thereto. These may be used alone or in combination of two or more.
Further, it is particularly preferable to use a total parasitic plant [Cistanche tubulosa: kankanikujuyo] among the plants of the genus Oleaceae.

Furthermore, the “extract” preferably contains a phenylethanoid glycoside. Here, the “phenylethanoid glycoside” is not particularly limited, but echinacoside, acteoside, 2′-acetylacetoside; campneoside I; campneoside II; cis Cistantubuloside A, B1, B2, C1, C2; crenatoside; decaffeoylacteoside; isoacteoside; rhodioloside; syringalide A 3′-α-L-rhamnopyranoside, tubuloside and the like. In this case, the above components may be included alone or in the form of a mixture of two or more.
Among these, it is preferable to contain at least one of echinacoside and acteoside, and further to contain both echinacoside and acteoside.

At this time, the content of echinacoside is not particularly limited, but 10 to 70 when the total mass of the extract of the plant of the family Crestaceae (for example, the total parasitic plant [Cistanche tubulosa]) is 100% by mass. It can be made into mass%, Preferably it is 15-50 mass%, More preferably, it is 20-40 mass%, More preferably, it can be 23-38 mass%.
Further, the content of acteoside is not particularly limited. However, when the total mass of the extract of the plant of the family Amaranthaceae is 100% by mass, it is 1 to 40% by mass, preferably 5 to 30% by mass, more preferably 7 to 20%. It can be made into the mass%, More preferably, it is 8-10 mass%.

  Here, the part of the plant of the Amaranthaceae extracted is not particularly limited, and may be any of leaves, roots, stems, and the like as long as a desired effect is obtained. Preferably, it is extracted from the stems of the genus Oleaceae, in particular fresh stems.

  The method for obtaining the extract from the plant of the genus Oleaceae is not particularly limited, and examples thereof include a solvent extraction method and a supercritical extraction.

Moreover, when extracting by a solvent extraction method, the solvent to be used is not specifically limited, However, It is preferable to use a polar solvent. Moreover, although the said polar solvent is not specifically limited, For example, water, methanol, ethanol, isopropanol, acetone, 1, 3- butylene glycol, ethylene glycol, propylene glycol, glycerol, acetic acid, ethyl acetate, ether etc. are mentioned. These may be used alone or in combination of two or more.
This is because it is possible to obtain an extract containing a high concentration of phenylethanoid glycoside, which is preferably subjected to further treatments such as dilution, concentration, drying and purification.
Examples of the purification method include activated carbon treatment, resin adsorption treatment, ion exchange resin, liquid-liquid countercurrent distribution, and the like.

One embodiment of a specific method for producing the extract is described in detail below. In addition, the manufacturing method of an extract is not limited to the following.
The manufacturing method of the said extract consists of two steps, extraction and refinement | purification. In the first stage, the stems of the genus Oleaceae (for example, the total parasitic plant [Cistanche tubulosa]), more preferably the fresh stems of the plant are cut into flakes, or Grind into powder. Next, the flakes, fine particles or powder thus obtained are immersed in a solvent such as water, a lower aliphatic alcohol such as ethanol or methanol, or a mixture thereof. At this time, the extraction is performed at room temperature. Next, the mixed solution is filtered, and the filtrate is concentrated under reduced pressure or in vacuo to obtain an extract. Next, as a second step, the extract is heated in water and then transferred to an adsorption column packed with D-101 type or AB-8 type macroporous adsorption resin to purify the extract. . At this time, the column is eluted using water, methanol, ethanol, a mixed solution of water and methanol, or a mixed solution of water and ethanol as an elution solvent. The elution may be carried out by using an elution solvent as described above in a solution having a constant concentration or by adding a concentration gradient to the solution. The eluate is collected and concentrated, and then dried by a known drying method. When the eluate has dried, the extract is obtained. The extract thus obtained contains a phenylethanoid glycoside.

  The skin photoaging preventive agent of the present invention can be used as a material for various foods and drinks. Examples of food and drink include edible oil (salad oil), confectionery (gum, candy, caramel, chocolate, cookie, snack, jelly, gummy, tablet confection etc.), noodles (soba, udon, ramen etc.), dairy products ( Milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports drinks, etc.) and health foods (tablets , Capsules, etc.) and nutritional supplements (nutrient drinks, etc.). It is recommended that the skin photoaging preventive agent of the present invention is appropriately blended with these foods and drinks.

These foods and drinks can be blended with various ingredients depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid. Acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used. These may be used alone or in combination of two or more.
In addition, this skin photoaging preventive with health maintenance function includes other antioxidants and health food ingredients such as antioxidants, reduced ascorbic acid (vitamin C), vitamin E, reduced Type glutatin, tocotrienol, vitamin A derivative, lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sezamin, lignans, catechins, isoflavones, chalcones, tannins , Flavonoids, coumarin, isocoumarins, blueberry extract, arbutin, tannin, anthocyanin, apple polyphenol, grape seed extract, ellagic acid, kojic acid, surge extract health food material, V. (vitamin) A, V.B1, V .B2, V.B6, V.B12, VC, VD, VE, VP Choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soy lecithin, taurine, donariella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium, potassium , Heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, turmeric, licorice, kokushi, keihi, hawthorn, ginger, ganoderma, rainbow trout extract, suppon, licorice, kokushiki, keihi, hawthorn, ginger, ganoderma , Psyllium, chamomile, chamomile, dandelion, hibiscus, honey, boren, royal jelly, lime, lavender, rosehip, rosemary, sage, bifidobacteria, faecalis, lacris, wheat germ oil, sesame oil, Soviet oil, soybean oil, medium-chain fatty acid, Agaricus, ginkgo biloba extract, turmeric, chondroitin, brown rice germ extract, litchi, onions, DHA, EPA, DPA,
甜 Tea, Cordyceps, Garlic, Bee, Papaya, Puaru, Propolis, Meguri Tree, Yabushitake, Royal Jelly, Saw Palmetto, Hyaluronic Acid, Collagen, Gabba, Harpseal Oil, Shark Cartilage, Glucosamine, Lecithin, Phosphatidylserine, Tabashi Carrot, mulberry leaf, soy extract, echinacea, sorghum, barley extract, olive leaf, olive fruit, gymnema, banaba, salacia, garcinia, chitosan, st jones wort, jujube, carrot, passion flower, broccoli, placenta, pearl barley, grape Seeds, peanut seed coat, bilberry, black cohosh, maria thistle, laurel, sage, rosemary, raffma, black vinegar, bitter gourd, maca, safflower, flax, oolong tea, flower spine, caffeine, capsaicin, xylo Ligo sugar, glucosamine, buckwheat, citrus, dietary fiber, protein, prunes, spirulina, barley young leaves, nucleic acid, yeast, shiitake, plum meat, amino acids, deep-sea cocoon extract, noni, oyster meat, suppon, champignon, plantain, acerola, Pineapple, Banana, Peach, Apricot, Melon, Strawberry, Raspberry, Orange, Fucoidan, Meshimakobu, Cranberry, Chondroitin sulfate, Zinc, Iron, Ceramide, Silk peptide, Glycine, Niacin, Chesttree, Ceramide, L-cysteine, L-Carnitine , Red wine leaf, millet, horsetail, biotin, Centella asiatica, lotus cup, pycnogenol, burdock, rhubarb, clove, rosemary, catechin, puer, citric acid, brewer's yeast, merirot, black zinger, ginger, guga Utsu, Nattokinase, Benikouji, Tocotrienol, Lactoferrin, Cinnamon, Persimmon Buckwheat, Cocoa, Yuzu Seed Extract, Perilla Seed Extract, Lychee Seed Extract, Evening Primrose Extract, Black Rice Extract, α-Lipoic Acid, Gabba, Raw Coffee Bean Extract, Fuquisa Extract Kiwi seed extract, Unshu orange extract, red ginger extract, astaxanthin) and the like can also be blended. These may be used alone or in combination of two or more.

  As a specific production method, the skin photoaging preventive agent of the present invention is spray-dried or freeze-dried as it is or with powdered dextrin, and this is easily converted into a powder, granule, tablet, or solution to produce food (instant food, etc.) ). Further, if necessary, it can be mixed with a binder such as gum arabic to form a powder or granules, and added to a solid food. Moreover, it is also possible to add to a beverage as it is or after being dispersed and dissolved in water, ethanol, glycerin or a mixture thereof.

  The skin photoaging preventive agent of the present invention may be used as a raw material for medicines (including pharmaceuticals and quasi drugs). It can be produced by appropriately blending the skin photoaging preventive agent of the present invention with a raw material for a pharmaceutical preparation. In addition, the said chemical | medical agent may be used for a human and may be used for mammals other than a human. Examples of the pharmaceutical raw material that can be blended in the skin photoaging preventive agent of the present invention include, for example, excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hydrogenated vegetable oil, kaolin, Talc, etc.), binder (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrant (sodium alginate, agar, carbonate) Sodium hydride, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers (No. Quaternary ammonium base, sodium lauryl sulfate ), Adsorbent (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, and the like) and the like. These may be used alone or in combination of two or more.

  The method for administering the skin photoaging preventive agent according to the present invention can generally be administered orally in the form of tablets, pills, soft / hard capsules, fine granules, powders, granules and the like. The water-soluble preparation can be administered orally as a liquid. Furthermore, parenteral administration may be used. When administered as a parenteral agent, the skin photoaging preventive agent of the present invention is dispersed in an appropriate solubilizing agent such as ethanol or water, and then an agent such as a poultice, lotion, ointment, tincture or cream. Can be applied in form. In addition, the water-soluble preparation of this skin photoaging preventive agent can be used as it is or with a dispersant, suspension, stabilizer, etc. added, such as a poultice, lotion, ointment, tincture or cream. Can be applied in form.

  The dosage may vary depending on the administration method, medical condition, age of the patient, etc., but for adults, it can usually be administered as an active ingredient per day from 5 to 400 mg, and for children, usually from about 0.5 to 200 mg.

The compounding ratio when using the skin photoaging preventive agent of the present invention as a drug can be appropriately changed depending on the dosage form, but is usually about 0.01 to 10 wt.% When administered orally or by mucosal absorption. %, In the case of parenteral administration, it should be about 0.01 to 20 wt%. In addition, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or it may be necessary to administer beyond the range. The pharmaceutical composition may include, in addition to the above-mentioned skin photoaging preventive agent, other known compounds commonly used in the pharmaceutical field and compounds necessary for molding into a form suitable for oral administration. Examples of such compounds include lactose, starch, hydroxypropyl cellulose, kaolin, talc, calcium carbonate and the like.

Moreover, the skin photoaging preventive agent of this invention can be contained in the animal feed for mammals. The animal feed can be contained in the same manner as the food and drink. The animal feed is not particularly limited. For example, it is used for domestic animals such as cattle and pigs, companion animals such as dogs, cats and hamsters (animals kept as pets). can do.
For example, flour, meat, etc. can be used as companion animal feed. At this time, examples of the flour include wheat flour, rice flour, rye flour, corn flour, millet flour, bubble flour, corn flour, and soybean flour, and these flours may be used in combination of two or more. By using flour, nutrients such as carbohydrates can be supplied to companion animals. Among the above flours, it is most preferable to use flour, and as flour, strong flour, medium flour, thin flour can be used alone or in combination, and even when such flour and other flour are used in combination Good. Furthermore, in order to adjust the elasticity of the animal feed after the heat treatment, wheat flour, wheat gluten, soybean protein and the like may be combined. In addition, the network structure derived from gluten contained in wheat flour can constitute a puffed tissue structure when heat-treated, which contributes to improving the texture.

  At this time, the meat to be used is not particularly limited, and chicken, pork, beef, mutton, goat meat, crab meat, turkey meat, horse meat, etc. can be used, but chicken is preferably used in terms of flavor. The The above meat is obtained by slaughtering and demolishing livestock in the usual way. In addition, since the deterioration of the quality of a product with intermediate moisture or low moisture is mainly caused by oxidation of fat, the meat used is preferably lean meat with little fat content or fat removed. In addition, the coexistence of meat can improve the palatability of companion animals as well as strengthening high quality animal proteins.

The companion animal feed can be prepared by various methods. As a preferred method, a kneaded raw material mixture (hereinafter referred to as “dough”) containing flour (preferably wheat flour) and meat is prepared and molded. Thereafter, a heat treatment method can be exemplified. The composition of flour and meat in the dough is not particularly limited, but is usually about 5 to 60% flour, preferably about 10 to 50%, about 5 to 80% meat, preferably about 20 to 50%, and the required amount. It is adjusted to consist of water. Moreover, when using Aw regulator, the said Aw regulator is added so that it may become about 5-30%, Preferably it is about 10-20%. In addition, what is necessary is just to adjust the usage-amount of water suitably according to usage-amounts, such as flour, meat, and Aw regulator, so that dough can be knead | mixed and shape | molded.
The method for preparing the dough is not particularly limited, but preferably the meat is first ground with a silent cutter, chopper, or the like. At this time, it is preferable to chop the chopped meat so that bubbles are sufficiently contained therein. Then, the flour-containing dough can be prepared by adding flour, water and, if necessary, an Aw adjusting agent to the finely ground meat and sufficiently kneading to contain bubbles. In preparing the dough, a foaming agent may be added. It is preferable to use a foaming agent, particularly when flour other than wheat flour is used as the flour. By adding the foaming agent, fine bubbles can be uniformly contained in the dough. Various foaming agents can be used as the foaming agent, but it is preferable to use a soy protein foaming agent and / or an enzyme-decomposed soybean protein foaming agent from the viewpoint of the stability of air bubbles.

The dough prepared in this manner is molded and heat-treated, whereby the companion animal feed of the present invention is obtained. The dough may be formed into an appropriate shape according to the ease of eating when the companion animal eats the companion animal feed of the present invention, the handling of the owner, etc., for example, plate shape, stick shape, Examples include a disk shape, a donut shape, and a heart shape. Also, from doughs prepared from the same formulation, dye them with pigments of different colors, or mix vegetables or fruits to prepare multiple doughs with different appearances, and combine them in a multilayer or concentric form You can also
The heating means for the molded dough is not particularly limited, and examples thereof include oven heating and microwave heating. These heating methods are known, and heat treatment may be performed according to a conventional method. The water content of the feed after the heat treatment is usually about 20 to 40%. By the above heat treatment, the dough swells due to the evaporation of water and the expansion of bubbles, and the water evaporates in a short time, so Aw is lowered and the storage stability is improved. Moreover, when wheat flour is used as the flour, the mesh structure derived from gluten contained in the wheat flour is fixed by heat treatment, and the texture is improved. In the case of oven heating, there is an advantage that a unique color tone (amber color) and aroma can be generated in the feed. On the other hand, in the case of microwave heating, it can be heated from inside the dough. There is an advantage that it can be uniformly expanded and a feed having uniform air bubbles can be obtained. In the above heat treatment, it is preferable to adjust so that the Aw of the obtained feed is in the range of 0.6 to 0.9. As described above, the storage stability of the feed can be remarkably improved by adjusting Aw to this range.

The above-mentioned companion animal feed thus obtained is a feed having a bread-like property and has a soft texture and moderate flexibility and elasticity, so that it is a companion with weak teeth such as a young dog, an old dog or a cat. Suitable as animal feed, snacks, etc. Of course, it can be used as a feed or a snack for healthy adult dogs and cats. The animal feed is produced by storing an appropriate amount in a packaging container and sealing it. As the packaging container, it is preferable to use an oxygen gas-impermeable packaging material. Examples of the packaging form include vacuum packaging, inert gas filling packaging, and the like, but it is preferable to carry out inert gas filling packaging together with an oxygen scavenger (for example, Ageless ^TM ). According to such a packaging form, it is possible to prevent quality deterioration and microorganism growth due to oxygen during the storage period.

Even if the skin photoaging preventive agent of the present invention is used as a skin external preparation (including cosmetics, pharmaceuticals and quasi drugs), it can be expected to have a skin photoaging preventive action. In addition, the said skin external preparation may be used for a human and may be used for mammals other than a human.
Examples of the external preparation for skin to which the skin photoaging preventive agent of the present invention can be formulated include, for example, emulsion, soap, facial cleanser, bath preparation, cream, emulsion, lotion, eau de cologne, shave cream, shave lotion. , Cosmetic oil, tan / sunscreen lotion, powder, foundation, perfume, pack, nail cream, enamel, enamel remover, eyebrow, blusher, eye cream, eye shadow, mascara, eyeliner, lipstick, lip balm, shampoo, Rinse, hair dye, dispersion liquid, cleaning agent and the like can be mentioned.
Examples of the form of a pharmaceutical or quasi-drug that can contain the skin photoaging preventive agent of the present invention include ointments, creams, and liquids for external use.

In addition to the skin photoaging preventive agent according to the present invention, the external preparation for skin of the above-described form includes components, oils and the like that are blended in skin external preparations such as cosmetics and quasi-drugs as long as the skin photoaging preventive action is not impaired Higher alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives, and the like.
Examples are listed below, but the present invention is not limited to these examples. Moreover, these may be used alone or in combination of two or more.

(1) Examples of oil components Ester-based oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearic acid Isocetyl, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine Diisopropyl acid, isoaralkyl neopentanoate, glyceryl tri (capryl / caprate), trimethylolpropane tri-2-ethylhexanoate, trimethylol triisostearate Propane, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isolaurate Stearyl, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl linoleate, octyldodecyl isoleate, isopropyl isostearate Cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethyleneglycol dioctanoate , Ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (capryl / capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, triisopalmitine Glyceryl acid, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyl decyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleic acid Ester, polyglycerol isostearate, dipropyl carbonate, charcoal Dialkyl (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyl decyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, Trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, olein Cholesteryl acid, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, 12-stearoyl hydroxystearate Cetyl, 12-stearoyl-hydroxystearic acid stearyl 12-stearoyl-hydroxystearic acid isostearate, and the like.
Hydrocarbon oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
Animal and vegetable oils and their hydrogenated oils, and naturally occurring waxes: beef tallow, hydrogenated beef tallow, lard, hydrogenated tallow, horse oil, hydrogenated horse oil, mink oil, orange luffy oil, fish oil, hydrogenated fish oil, egg yolk oil and other animal oils and Its hardened oil, avocado oil, almond oil, olive oil, cacao butter, kiwi seed oil, apricot oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil , Perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, hydrogenated rapeseed oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil , Vegetable oils such as sunflower oil, grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, medhome oil, cottonseed oil, hardened cottonseed oil, coconut oil, hardened coconut oil and its hardened , Beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and montan wax.
Silicone oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethyl Siloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic Examples include silicone, trimethylsiloxysilicic acid, and silicone RTV rubber.
Fluorine oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, and the like.

(2) Examples of higher alcohols Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol and the like can be mentioned.

(3) Examples of fatty acids Caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid , Erucic acid, 2-ethylhexanoic acid and the like.

(4) Examples of UV absorbers Paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, salicylic acid Octyl, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, mono 2-diparamethoxycinnamate Glyceryl ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamic acid, diisopropyl diisopropylcinnamic acid Stealth mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, Butylmethoxydibenzoylmethane, 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1,3,5-triazine, 2- (2-hydroxy-5-methylphenyl) benzotriazole , Methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, phenylbenzimidazole sulfate, 3- (4-methylbenzylidene) can Examples include full, isopropyldibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2, 5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like, polymer derivatives, silane derivatives, and the like.

(5) Examples of powders and pigments Red 104, Red 201, Yellow 4, Blue 1, Black 401 and other dyes, Yellow 4 AL lake, Yellow 203 BA lake and other lake dyes, nylon powder , Silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder, yellow iron oxide, red iron oxide, black Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide and cerium oxide, extender pigments such as talc, mica, sericite, kaolin and barium sulfate plate, titanium mica Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, metal salts such as magnesium silicate, Inorganic powders such as Rica and alumina, metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, zinc undecylenate, bentonite, smectite, boron nitride, etc. It is done. There are no particular restrictions on the shape of these powders (spherical, rod-like, needle-like, plate-like, irregular shape, flake-like, spindle-like, etc.) and particle diameter. These powders are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, The surface treatment may or may not be performed in advance by polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment or the like.

(6) Examples of surfactants Anionic surfactants: fatty acid soap, α-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate , Alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate, alkyloylalkyl taurine salt, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, alkyl sulfoacetic acid Sodium, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate, etc. are mentioned.
Cationic surfactant: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride , Behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, and the like.
Amphoteric surfactants: carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type and the like.
Nonionic surfactant: propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbitol fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE cured castor Oil, POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, and the like.
Natural surfactant: lecithin, saponin, sugar surfactant and the like.

(7) Examples of polyhydric alcohols and sugars Ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1, 3 -Butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan and the like. These chemically modified compounds can also be used.

(8) Examples of polymers Acrylic ester / methacrylic acid ester copolymer (plus size, manufactured by Kyoyo Chemical), vinyl acetate / crotonic acid copolymer (resin 28-1310, manufactured by NSC), vinyl acetate / croton Acid / vinyl neodecanate copolymer (28-2930, manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (rubymer) , BASF), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Rubicol VAP, BASF), vinyl acetate / crotonic acid copolymer (Rubiset CA, BASF), vinyl acetate / croton Acid / vinyl pyrrolidone copolymer (Rubiset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Rubiflex, BA SF), acrylate / acrylamide copolymer (Ultrahold, BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, ISP), carboxy vinyl polymer (Carbopol, BF Goodrich), anionic polymer compounds such as acrylic acid / alkyl methacrylate copolymers (Pemulene, BF Goodrich) and acetic acid amphoteric compounds of dialkylaminoethyl methacrylate polymers (Yukaformer, Mitsubishi Chemical) Amphoteric polymer compounds such as octyl acrylate acrylate / hydroxypropyl acrylate / butyl aminoethyl methacrylate copolymer (AMPHOMER, NSC), quaternized vinylpyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT, ISP) , Methyl vinyl imidazolium chloride Cationic polymer compounds such as vinyl / vinylpyrrolidone copolymer (rubicoat, manufactured by BASF), polyvinylpyrrolidone (rubiscol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (rubiscol VA, manufactured by BASF) ), Nonionic polymer compounds such as vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP), vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP), etc. There is. Cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabino Naturally derived polymer compounds such as galactan, gum karaya, gum tragacanth, alginic acid, albumin, casein, curdlan, gellan gum and dextran can also be suitably used.

(9) Examples of physiologically active ingredients Examples of physiologically active ingredients include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening ingredients, immunostimulants, anti-aging agents, UV protection agents, slimming agents, tanning agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, desiccants, A cooling sensation agent, a warming sensation agent, vitamins, an amino acid, a wound healing promoter, an irritation relaxation agent, an analgesic agent, a cell activator, an enzyme component, etc. are mentioned. Examples of these suitable ingredients include, for example, ashitaba extract, avocado extract, amateur extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, ages Extract, Echinacea leaf extract, Ogon extract, Oat extract, Oen extract, Barley extract, Hypericum extract, Oyster extract, Dutch mustard extract, Orange extract, Seawater dried product, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk , Chamomile extract, Carrot extract, Kawara mugwort extract, Licorice extract, Calcade extract, Oyster extract, Kina extract, Cucumber extract, Guanosine, Gardenia extract, Kumazasa extract, Clarae Kiss, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentian extract, tea extract, yeast extract, burdock extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, bilberry extract, saicin extract, psycho extract Extract Kizuta extract, hawthorn extract, elderberry extract, yarrow extract, mint extract, sage extract, mallow extract, senki Sue extract, assembly extract, soybean extract, tiso extract, thyme extract, tea extract, clove extract, chigaya extract, chimpi extract, touki extract, toshinsen extract, tonin extract, spruce extract, dokudami extract, tomato extract, natto extract, carrot extract, garlic extract, Novara extract, hibiscus extract, bacmond extract, parsley extract, honey, hamamelis extract, parietalia extract, toad extract, bisabolol, loquat extract, dandelion extract, burdock extract, bukuro extract, butcher bloom extract, grape extract, propolis, loofah extract, Safflower extract, peppermint extract, bodaige extract, button extract, hop extract, pine extract, marronnier extract, mizubasho Kiss, Mukuroji extract, Melissa extract, Peach extract, Cornflower extract, Eucalyptus extract, Yukinoshita extract, Yokuinin extract, Artemisia extract, Lavender extract, Apple extract, Lettuce extract, Lemon extract, Lotus root extract, Rose extract, Rosemary extract, Roman chamomile extract And royal jelly extract.
Biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate , Moisturizing ingredients such as betaine, whey, trimethylglycine, oily ingredients such as sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, Immunostimulants such as hydrocortisone, vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester Vitamins, active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoid, flavonoid, tannin, lignan, saponin, α-hydroxy acid, β-hydroxy acid, etc. Cell activators, blood circulation promoters such as γ-oryzanol and vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione, etc. Whitening agent, cephalanthin, licorice extract, red pepper tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivative, calcium pantothenate, D-pan Tothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid vanillylamide, nonanoic acid vanillylamide, pyroctone Olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormone, cantalis tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, monostearic acid Examples include hair growth agents such as polyoxyethylene sorbitan, mint oil, and Sasanishiki extract.

(10) Examples of antioxidants: sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolyl biguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxy Examples include plant extracts having an antioxidant effect such as toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoid, flavonoid, tannin, lignan, saponin, apple extract and clove extract.

(11) Examples of solvents Purified water, ethanol, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, next-generation chlorofluorocarbon and the like.

Examples of the present invention will be described, but the present invention is not limited to these examples.
Examples Preparation of skin photoaging preventive agent of the present invention Example 1 Preparation of an extract of all parasitic plants [Cistanche tubulosa] (hereinafter simply referred to as “kankanikujuyo”) <Extraction process>
A fresh stalk flake of Kankaniku Juyo was immersed in 8 times the amount of water of the flake. The flakes were soaked in water for 1 hour and then decocted with water for 2 hours. The mixture brewed in this way was filtered to obtain a first filtrate. Next, the residue of the decocted mixture was mixed with 40% ethanol of 4 times the residue, decocted for 4 hours, and the decocted mixture was filtered to obtain a second filtrate. About the residue of the 2nd filtrate, the same operation as the above was repeated twice, and the 3rd and 4th filtrate was obtained. These four kinds of filtrates were combined and concentrated in vacuo so that the specific gravity was 1.05 (50 ° C.), thereby obtaining a final extract. The final extract thus obtained weighed 6.2 kg.

<Purification process>
6 kg of the final extract was dissolved in half the amount of water of the final extract while heating. The extract solution was then placed on an adsorption column packed with pre-treated macroporous adsorption resin of D-101 type. The column is first eluted with water to obtain twice the amount of fresh water eluate, and the column is further eluted with 20% ethanol to double the amount of fresh stem first 20% ethanol eluate. Got. The water eluate was subjected to the adsorption-desorption operation again to obtain a second ethanol eluate. These two 20% ethanol eluates were combined, concentrated and dried to obtain a preparation containing phenylethanoid glycoside (Example 1). The weight of the preparation thus obtained was 0.865 kg.

  The contents of echinacoside and acteoside were measured by high performance liquid chromatography (HPLC). At this time, the HPLC conditions are as follows. The stationary phase was C18 alkylsilane silicone, the mobile phase was methanol-0.15% acetic acid aqueous solution (30:70), the flow rate was 1 ml / min, and the detection wavelength was 330 nm.

  The echinacoside and acteoside dried in vacuum at 60 ° C. for 24 hours were measured and dissolved in 50% methanol to prepare a reference solution (each 1 ml solution contains 0.1 mg of solute).

  The test solution was prepared by dissolving a preparation containing 50 mg of phenylethanoid glycoside in an appropriate amount of 50% methanol in a 25 ml graduated container while sonicating. Then, 50% methanol was added to the solution up to a 25 ml scale. Thereafter, about 1 ml of this solution was accurately taken and transferred to a container with a 10 ml scale, and 50% methanol was added to the 10 ml scale. Thereafter, this solution was filtered through a 0.45 μm membrane to obtain a test solution.

  5 μl of each of the reference solution and the test solution was taken and injected into a liquid chromatography column, and the peak areas of echinacoside and acteoside were measured. The content was calculated using these peak areas. As a result, the content of echinacoside was 29.3% by mass of the preparation (Example 1), and the content of acteoside was 10.0% of the preparation (Example 1).

Test example 1
Method:
Hairless mice were divided into the following 3 groups (n = 4).
・ No UV group ・ UV + solvent administration group ・ UV + Kanka 200 mg / kg administration group

At this time, in the “UV + kanka 200 mg / kg administration group”, hairless mice were forcibly orally administered 200 mg / kg of the aqueous solution of the preparation of Example 1 once a day for 6 consecutive weeks. In the “UV + solvent administration group”, distilled water is forcibly orally administered once a day for 6 weeks in place of the aqueous solution of the preparation of Example 1, and the “no UV group” is administered by gavage. Did not do. At this time, the UV + Kanka 200 mg / kg administration group and the UV + solvent administration group were irradiated with UV three times a week for 6 weeks (1 week: 50 mJ / cm ² ,
Week 2: 70 mJ / cm ² , 3 and 4
Week: 80 mJ / cm ² , 5 and 6 weeks: 200 mJ / cm ² ). In addition, the “no UV group” was not irradiated with UV, and the preparation of Example 1 and the forced oral administration of distilled water were not performed, and the “UV + kanka 200 mg / kg administration group” and “ The animals were reared for 6 weeks in the same environment as the “UV + solvent administration group”.

In each of the above groups, a replica of the back of the hairless mouse was collected using SKIN CAST 6 weeks after administration. After taking the collected replica under certain conditions using USB Microscope M2, image analysis software (NIH
Image) was used to measure and evaluate the wrinkle area before and after ingestion (NIH Image analysis area value). The result is shown in FIG. The “NIH Image analysis area” is a value indicating the area of wrinkles in the image analysis software used in this test example, and the larger this value, the larger the area of wrinkles in the skin. . In FIG. 1, “NO-UV” indicates the results of the no UV group, “Cont. (UV)” indicates the results of the UV + solvent administration group, and “200” indicates the results of the UV + kanka 200 mg / kg administration group.

Effect of Example in Test Example 1 According to FIG. 1, “UV + Kanka 200”
In the “mg / kg administration group”, there was a tendency to suppress wrinkle formation due to ultraviolet irradiation. Thereby, it was confirmed that the preparation of a present Example effectively prevents the production | generation of the wrinkle resulting from ultraviolet irradiation.

Test example 2
Method In the hairless mice of the group used in Test Example 1 above, the skin of each group of hairless mice 6 weeks after administration was collected, RNA of the skin was extracted, hyaluronidase and collagenase by RT-PCR after reverse transcription reaction The expression level of each gene in was compared. The results are shown in FIG. 2 (hyaluronidase gene expression) and FIG. 3 (collagenase gene expression). 2 and 3, “NO-UV” indicates the results of the no UV group, “Cont. (UV)” indicates the results of the UV + solvent administration group, and “200” indicates the results of the UV + kanka 200 mg / kg administration group.

Effect of Example in Test Example 2 According to FIG. 2 and FIG. 3, as a result of comparing the expression levels of hyaluronidase and collagenase gene by RT-PCR, hyaluronidase gene by UV irradiation in Kanka extract (200 mg / kg) (FIG. 2) And the effect | action which suppresses the expression level of a collagenase gene (FIG. 3) was recognized. This is the same tendency as the effect on wrinkle formation shown in Fig. 1. This suggests that Kanka extract suppresses wrinkle formation by suppressing the expression of skin aging genes. From the above results, it was confirmed that Kanka extract suppresses the skin aging phenomenon caused by ultraviolet irradiation.

Although the compounding example of the skin photoaging preventive agent of this invention is given to the following, the following compounding example does not limit this invention.
Formulation Example 1: Chewing gum
53.0wt% sugar
Gum base 20.0
Glucose 10.0
Minamata 16.0
Fragrance 0.5
Skin photoaging preventive agent 0.5
100.0wt%

Formulation Example 2: Gummy
Reduced water tank 40.0wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Grape juice 4.0
Grape flavor 0.6
Dye 0.02
Skin photoaging preventive agent 1.0
100.0wt%

Formulation Example 3: Candy
50.0 wt% sugar
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Skin photoaging preventive agent 0.4
100.0wt%

Formulation Example 4: Yogurt (hard / soft)
Milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Skin photoaging preventive agent 0.4
Perfume
Water residue
100.0wt%

Formulation Example 5: Soft drink
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Skin photoaging preventive agent 0.05
Perfume
Purified water residue
100.0wt%

Formulation Example 6: Tablets
76.4 wt% sugar
Glucose 19.0
Sucrose fatty acid ester 0.2
Skin photoaging preventive agent 0.5
Purified water 3.9
100.0wt%

Formulation Example 7: Soft capsule
Grape seed oil 87.0wt%
Emulsifier 12.0
Skin photoaging preventive agent 1.0
100.0wt%

Formulation Example 8: Tablet
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch degradation product 10.0
Glycerin fatty acid ester 5.0
Skin photoaging preventive agent 1.0
100.0wt%

Formulation Example 9: Oral granules (pharmaceuticals)
Skin photoaging preventive agent 1.0wt%
Lactose 30.0
Cornstarch 60.0
Crystalline cellulose 8.0
Polyvinylpyrrolidone 1.0
100.0wt%

Formulation Example 10: Cosmetic cream
Squalane 20.0wt%
Beeswax 5.0
Refined jojoba oil 5.0
Glycerin 5.0
Glycerol monostearate 2.0
Polyoxyethylene (20) sorbitan-
Monostearate 2.0
Skin photoaging preventive agent 2.0
Preservative appropriate amount
Perfume
Purified water residue
100.0wt%

Formulation Example 11: Lotion
Ethanol 5.0wt%
Glycerin 2.0
1,3-butylene glycol
2.0
Polyethylene oleyl ether 0.5
Sodium citrate 0.1
Citric acid 0.1
Skin photoaging preventive agent 0.1
Purified water residue
100.0wt%

Formulation Example 12: Body gel
Macadamia nut oil 2.0wt%
Octyldodecyl myristate 10.0
Methylphenylpolysiloxane 5.0
Behenyl alcohol 3.0
Stearic acid 3.0
Batyl alcohol 1.0
Glyceryl monostearate 1.0
Tetraoleic acid polyoxyethylene sorbit 2.0
Hydrogenated soybean phospholipid 1.0
Ceramide 0.1
Retinol palmitate 0.1
Preservative appropriate amount
Centella extract 1.0
Skin photoaging preventive agent 1.0
1,3-butylene glycol 5.0
Purified water residue
100.0wt%

Formulation Example 13: Latex
Squalane 4.0wt%
Vaseline 2.5
Cetanol 2.0
Glycerin 2.0
Lipophilic glyceryl monostearate 1.0
Stearic acid 1.0
L-Arginine 1.0
Skin photoaging preventive agent 0.5
Potassium hydroxide 0.1
Perfume
Purified water residue
100.0wt%

Formulation Example 14: Bath agent (liquid)
Propylene glycol 50.0wt%
Ethanol 20.0
Sodium sulfate 5.0
Skin photoaging preventive agent 0.5
Lanolin 0.5
Avocado oil 0.5
Dye 1.5
Fragrance 22.0
100.0wt%

Formulation Example 15: Cat food
Corn 34.0wt%
Flour 35.0
Meat meal 15.0
Beef tallow 8.9
Salt 1.0
Skipjack extract 4.0
Skin photoaging preventive agent 1.0
Taurine 0.1
Vitamins 0.5
Minerals 0.5
100.0wt%

Formulation Example 16: Dog food
Corn 30.0wt%
Meat (chicken) 15.0
Defatted soybean 10.0
Flour 25.0
Mosses 5.0
Skin photoaging preventive agent 5.0
Animal fats and oils 8.9
Oligosaccharide 0.1
Vitamin 0.5
Mineral 0.5
100.0wt%

  As described above, the present invention suppresses the formation of wrinkles in hairless mice irradiated with ultraviolet rays, and further suppresses the expression of skin aging-related genes (hyaluronidase, collagenase) in hairless mice irradiated with ultraviolet rays. Thus, it is understood that a novel skin photoaging preventive agent is provided, and further, foods using the same, pharmaceutical products for mammals including humans and external preparations for skin, and feed for mammalian animals are provided.

In a present Example, it is a graph which shows the relationship between hairless mouse ultraviolet irradiation and a wrinkle area. It is a graph which shows the influence of a hyaluronidase gene expression in a present Example. It is a graph which shows the influence of collagenase gene expression in a present Example.

Claims (11)

A skin photoaging preventive agent comprising a phenylethanoid glycoside as an active ingredient. The skin photoaging preventive agent according to claim 1, wherein the phenylethanoid glycoside contains at least one of echinacoside and acteoside. 3. The skin photoaging preventive agent according to claim 2, comprising echinacoside and acteoside as the phenylethanoid glycoside. An agent for preventing skin photoaging, comprising an extract of a plant of the genus Crestaceae as an active ingredient. 5. The skin photoaging preventive agent according to claim 4, wherein the extract contains phenylethanoid glycoside as an active ingredient. 6. The skin photoaging preventive agent according to claim 5, wherein the extract contains at least one of echinacoside and acteoside as the phenylethanoid glycoside. The skin photoaging preventive agent according to claim 6, wherein the extract contains echinacoside and acteoside as the phenylethanoid glycoside. A medicinal product for mammals including humans, comprising the skin photoaging preventive agent according to any one of claims 1 to 7 as an active ingredient. A skin external preparation for mammals including humans, comprising the skin photoaging preventive agent according to any one of claims 1 to 7 as an active ingredient. Food-drinks which use the skin photoaging preventive agent of any one of Claims 1-6 as an active ingredient. Mammal animal feed comprising the skin photoaging preventive agent according to any one of claims 1 to 7 as an active ingredient.