WO2016111276A1 - Sphingolipid absorption promoter - Google Patents
Sphingolipid absorption promoter Download PDFInfo
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- WO2016111276A1 WO2016111276A1 PCT/JP2016/050071 JP2016050071W WO2016111276A1 WO 2016111276 A1 WO2016111276 A1 WO 2016111276A1 JP 2016050071 W JP2016050071 W JP 2016050071W WO 2016111276 A1 WO2016111276 A1 WO 2016111276A1
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- sphingolipid
- sphingomyelin
- absorption
- lactic acid
- milk
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
Definitions
- the present invention relates to a sphingolipid absorption promoter (Absorption Promoter of Sphingolipid).
- the present invention also relates to a composition for oral ingestion or enteral administration comprising a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria and an additional sphingolipid.
- Sphingolipid is a component that constitutes eukaryotic cell membranes, and is a generic name for lipids having sphingoid bases. It has been clarified that the effect of improving the barrier function of the skin based on oral ingestion.
- Sphingomyelin is one of milk-derived sphingolipids.
- preventive and improving effects on skin conditions decrease in skin barrier function, dryness and roughness of skin, decrease in water content of stratum corneum, atopic dermatitis, etc.
- ingestion Etc. have been revealed.
- Sphingomyelin is a substance composed of ceramide and phosphocholine and is hydrolyzed to ceramide and phosphocholine by sphingomyelinase. Furthermore, ceramide is hydrolyzed by ceramidase into sphingoid bases and fatty acids, many of which are absorbed as fatty acids by epithelial cells of the small intestine, and some sphingoid bases are converted into sphingomyelin, ceramide, etc. Recombined. It has been suggested that sphingomyelin is degraded by enteric bacteria.
- Glucosylceramide is a substance in which glucose is bound to ceramide composed of sphingo base and fatty acid. It is hydrolyzed to ceramide and glucose by glucoceramide-degrading enzyme.
- Galactosylceramide is a substance in which galactose is bound to ceramide composed of a sphingo base and a fatty acid.
- lipids when taken orally, they are emulsified by bile acids, decomposed into fatty acids and monoglycerides by lipase, and absorbed in the small intestine. Furthermore, monoglycerides are re-synthesized into triacylglycerol in the epithelial cells of the small intestine, converted into chylomicrons, sent to the lymphatic vessels, pass through the thoracic duct, and then enter the systemic circulation.
- sphingomyelin and ceramide have low digestibility and absorption. Possible causes include the low activity of sphingomyelinase in the gastrointestinal tract and the elimination of sphingoid bases once absorbed by the transporter expressed there.
- Patent No. 3920969 proposes a nutritional composition containing bile acids and bile salts in order to improve the digestion and absorption of lipids.
- sphingolipids it does not describe sphingolipids here, and bile acids themselves are bitter, and their effects must be taken into account when used as food.
- Fermented milk is a fermented food prepared by mixing lactic acid bacteria and yeast in milk and fermenting it, and is widely eaten from the viewpoint of its deliciousness, beauty and health.
- Japanese Patent Application Laid-Open No. 7-327633 discloses a chitosan processed food in which chitosan, wheat and wheat yogurt are mixed.
- powdered yogurt has a function of assisting in digestion and absorption of chitosan.
- the digestive absorption function here focuses on the action of active lecithin in powdered yogurt, and there is no disclosure or suggestion about the promotion of digestive absorption of sphingolipids.
- the present inventors have unexpectedly found that when fermented milk (yogurt) is ingested simultaneously with sphingomyelin, the amount of sphingomyelin absorbed can be increased, that is, the absorption of sphingomyelin is improved unexpectedly. I also found. At this time, the present inventors have also found that absorption of ceramide is improved. From these facts, the present inventors have found that absorption of sphingolipids can be promoted by ingestion of fermentation products and / or cultures of lactic acid bacteria and / or bifidobacteria.
- the skin barrier function expected with the absorption of sphingolipids is improved, and various beneficial effects and effects are improved.
- the present inventors actually improved the amount of sphingomyelin absorbed into the living body by preparing an oral or enteral composition containing yogurt and sphingomyelin exceeding the yogurt content. confirmed.
- the present invention is based on these findings.
- the present invention is a means capable of improving or promoting the absorption of sphingolipids when ingesting sphingolipids, which is safe, simple and economical (or efficient).
- the purpose is to provide.
- a sphingolipid absorption promoter comprising as an active ingredient a fermentation product and / or culture product of lactic acid bacteria and / or bifidobacteria.
- the sphingolipid is sphingomyelin, and it is preferable to promote absorption of the sphingomyelin into the living body.
- sphingolipid absorption promoter of ⁇ 2> it is preferable to promote absorption of milk-derived sphingomyelin into the living body.
- the sphingolipid may be any one or more of ceramide, glucosylceramide, and galactosylceramide.
- the fermented product and / or culture product of lactic acid bacteria and / or bifidobacteria is a milk fermented product of lactic acid bacteria and / or bifidobacteria and / or Or it may be a milk culture.
- a sphingolipid absorption promoter comprising a polysaccharide as an active ingredient.
- a composition for oral ingestion or enteral administration comprising the sphingolipid absorption promoter according to any one of ⁇ 1> to ⁇ 6> above and a sphingolipid.
- a composition for oral ingestion or enteral administration comprising a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria and an additional sphingolipid.
- composition for oral ingestion or enteral administration according to ⁇ 7> or ⁇ 8> above, wherein the blending ratio of the lactic acid bacteria and / or bifidobacteria fermented product and / or culture product to the sphingolipid is a sphingolipid.
- 1 mg of lactic acid bacteria and / or bifidobacteria fermented and / or cultured may be included at 1 to 10,000 mg.
- the blending ratio of the lactic acid bacteria and / or bifidobacteria fermented product and / or culture product to the sphingolipid is determined as a sphingolipid.
- 1 mg of lactic acid bacteria and / or bifidobacteria fermented and / or cultured (wet weight) may be included in an amount of 0.01 to 100 g.
- the sphingolipid may be sphingomyelin.
- composition for oral intake or enteral administration according to any one of the above ⁇ 7> to ⁇ 11> is used for an in vivo action induced by absorption of sphingomyelin into the living body. Good.
- the in vivo action of ⁇ 7> is prevention or improvement of skin condition deterioration, cancer suppression action, skin beautification, infant brain It is preferable to be selected from the group consisting of a development promoting action, a mitochondrial function improving action, a motor function improving action, a visceral fat accumulation suppressing action and a blood adiponectin concentration raising promoting action, and an infectious disease preventing action.
- composition for oral intake or enteral administration according to any one of the above ⁇ 7> to ⁇ 11> may be used for prevention, suppression or improvement of skin condition deterioration.
- the deterioration of the skin state may be a deterioration of the skin barrier function.
- a food or drink comprising the sphingolipid absorption promoter of any one of ⁇ 1> to ⁇ 6> or the composition of any one of ⁇ 7> to ⁇ 15>.
- the food and drink according to ⁇ 16> may be a functional food, a health nutrition food, a supplement, a food for specified health use, a functional display food, or a food with a disease risk reduction display.
- the sphingolipid may be sphingomyelin.
- the absorption of sphingomyelin can be improved or promoted, and further, safe, simple and economical (or efficient) sphingomyelin. Can be absorbed.
- the yogurt used in the absorption enhancer and composition of the present invention has experience in use as a conventional food, so it is highly safe, simple in actual consumption, and economically advantageous. is there.
- FIG. 5 is a graph showing the results of Example 4 (area under the time curve of the amount of ceramide molecular species in serum) (in the figure, * means that there is a significant difference (P ⁇ 0.05) from the MPL group). , # Means that there is a significant difference (P ⁇ 0.05) with respect to the unfermented milk group).
- the sphingolipid absorption enhancer of the present invention contains a fermentation product and / or culture product of lactic acid bacteria and / or bifidobacteria as an active ingredient.
- active ingredient means that the absorption promoter according to the present invention is used in a sufficient amount (ie, effective amount) of lactic acid bacteria and / or sufficient to exert the action of promoting the absorption of sphingolipids in vivo. It means containing a fermented product and / or culture product of bifidobacteria.
- “absorption promotion” of sphingolipid means promoting absorption of the sphingolipid into the living body.
- the term “absorption” as used herein typically refers to a sphingolipid that has been orally or enterally administered simultaneously or sequentially with the absorption enhancer of the present invention, or a sphingolipid that has already been ingested into the body. It is taken up into the circulatory organs (vascular system and lymphatic system) in the living body through the biological membrane in the digestive tract and the absorption tract, etc., so that the actually absorbed sphingolipid is sphingolipid or its induction. As a substance, it is possible to exert various actions on the living body.
- promotion means that the absorption of sphingolipids is promoted compared to the case where no absorption enhancer is used.
- the amount of absorption increases and the rate of absorption is increased. Includes improving, improving reduced absorption and the like.
- promotion is used in the sense of increasing the amount of sphingolipid absorbed into the living body.
- sphingolipids are naturally derived, such as those derived from milk such as cow's milk, goat milk, sheep milk, and horse milk, those derived from egg yolk, those derived from soybeans, rice, corn, and grains. , Derived from konjac, beet-derived and the like, preferably derived from milk, more preferably derived from milk. Sphingolipids include sphingomyelin, glucosylceramide, and galactosylceramide. The sphingolipid is preferably a sphingophospholipid, more preferably a sphingomyelin. These can be prepared from natural raw materials by a conventional method, but commercially available products may be used.
- the sphingomyelin that can be used is one of sphingolipids and, like the sphingolipids described above, is naturally derived, preferably milk-derived, more preferably milk-derived. belongs to. Sphingomyelin can be prepared from natural raw materials by a conventional method, but a commercially available product may be used.
- absorption of milk-derived sphingomyelin into the living body is promoted in the sphingolipid absorption promoter.
- the absorption of sphingolipid can be evaluated by measuring the amount of sphingolipid into the living body.
- the absorption of sphingomyelin may be evaluated by paying attention to a certain molecular species of sphingomyelin and measuring the amount of the molecular species taken into the living body.
- the absorption of sphingomyelin can be evaluated by measuring the amount of a sphingomyelin inducer, for example, ceramide produced by hydrolysis of sphingomyelin, taken into the living body.
- examples of molecular species contained in sphingomyelin, particularly milk-derived sphingomyelin include the following: That is, it is a sphingomyelin molecular species in which phosphocholine or phosphoethanolamine is bound to a ceramide structure in which sphingosine or dihydrosphingosine having a carbon chain number of 16 to 18 and a fatty acid having a carbon chain of 14 to 26 are amide-bonded respectively.
- the absorption of sphingomyelin can be evaluated by focusing on one or a combination of a plurality of these molecular species and measuring the amount or the amount of the inducer.
- sphingomyelin is a substance composed of ceramide and phosphocholine, and is hydrolyzed into ceramide and phosphocholine by sphingomyelinase. Ceramide is further hydrolyzed to sphingoid base and fatty acid by ceramidase.
- the sphingolipid absorption promoter promotes the absorption of sphingomyelin and also promotes the absorption of ceramide into the living body.
- absorption of ceramide into the living body is also promoted.
- an absorption promoter for ceramide, glucosylceramide, and / or galactosylsalamide containing a fermentation product and / or culture product of lactic acid bacteria and / or bifidobacteria as an active ingredient.
- a ceramide, glucosylceramide, and / or galactosylsalamide lipid absorption enhancer according to the present invention, absorption of ceramide, glucosylceramide, galactosylsalamide, or a combination of two or more thereof into a living body is also promoted.
- examples of the molecular species contained in ceramide, glucosylceramide, and galactosylceramide include the following: That is, ceramide molecular species in which sphingosine, dihydrosphingosine, sphingadienin, phytosphingosine or hydroxysphingenin having 16 to 18 carbon chains and amide bonds of fatty acids or hydroxy fatty acids having 14 to 26 carbon chains, respectively.
- the “fermented product and / or culture of lactic acid bacteria and / or bifidobacteria” means a fermented product of lactic acid bacteria and bifidobacteria, a fermented product of lactic acid bacteria, a fermented product of bifidobacteria, a cultured product of lactic acid bacteria and bifidobacteria, Used to include lactic acid bacteria cultures, bifidobacteria cultures, and combinations thereof.
- lactic acid bacteria is a general term for microorganisms that assimilate glucose and produce lactic acid with a yield of sugar of 50% or more. It has characteristics such as lack of spore formation and negative catalase. Lactic acid bacteria have been eaten from around the world through fermented milk since ancient times, and can be said to be extremely safe microorganisms. To date, lactic acid bacteria have been classified into 11 genera of Lactococcus, Lactobacillus, Leuconostoc, Pediococcus, Streptococcus, Wissella, Tetragenococcus, Oenococcus, Enterococcus, Vagococcus, and Carnobacterium.
- Lactobacillus includes, for example, Lactobacillus genus, that is, Lactobacillus eckdelbrueckii subsp. Bulgaricus, Streptococcus thermophilus, Lactobacillus lactis, Lactobacillus gasseri and the like. In particular, it is preferable to use a mixed starter of Lactobacillus delbrueckii subsp. Bulgaricus and Streptococcus thermophilus.
- Bifidobacterium is a microorganism that assimilates glucose to produce acetic acid and lactic acid, and belongs to the genus Bifidobacterium. Examples include Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium adolescentis, Bifidobacterium breve and the like.
- the lactic acid bacteria include a combination of Bulgarian bacteria and thermophilus bacteria, and more preferably a combination of Bulgarian bacteria and thermophilus bacteria.
- the “fermented product” refers to a culture itself obtained by fermentation with lactic acid bacteria and / or bifidobacteria.
- “fermented product” refers to a fermented product of lactic acid bacteria and / or bifidobacteria and a processed product thereof, for example, the culture (lactic acid bacteria and / or bifidobacteria fermented product) removed by filtration, centrifugation, membrane separation, or the like.
- the culture filtrate or culture supernatant obtained by fungi the culture filtrate / culture supernatant, lactic acid bacteria and / or bifidobacteria fermentation product, etc. Heat, reduced pressure, etc.
- the above-described processing steps such as sterilization treatment such as filtration, centrifugation, and membrane separation, precipitation, concentration, pasting, dilution, and drying are combined. Can be used.
- examples of the culture medium include nonfat dry milk medium and MRS medium supplemented with yeast extract.
- the “fermented product and / or culture of lactic acid bacteria and / or bifidobacteria” is a fermented milk and / or milk culture of lactic acid bacteria and / or bifidobacteria.
- the “fermented product and / or culture product of lactic acid bacteria and / or bifidobacteria” is fermented milk (yogurt).
- the yogurt may be a supernatant thereof.
- the “fermented product and / or culture of lactic acid bacteria and / or bifidobacteria” is a polysaccharide.
- the polysaccharide is preferably derived from a fermentation product and / or a culture product.
- a sphingolipid absorption promoter comprising a polysaccharide as an active ingredient is provided.
- milk fermented product and / or milk culture refers to a product obtained by fermenting or culturing a raw material containing milk.
- milk include animal milk such as cow milk and processed products thereof (eg, skim milk, whole milk powder, skim milk powder, spinach, casein, whey, fresh cream, compound cream, butter, buttermilk powder, etc.) And vegetable milk such as soybean milk derived from soybean.
- fermented milk raw material mix As a raw material of fermented milk, what is called fermented milk raw material mix is mentioned, for example.
- the fermented milk raw material mix is a mixture containing raw milk and other ingredients, such as raw milk, water, and other optional ingredients (for example, sugar, sugar, sweetener, acidulant, mineral, vitamin, flavor, etc.) It can obtain by heating, melt
- Fermented milk can use thickeners and gelling agents such as pectin, guar gum, xanthan gum, carrageenan, and processed starch in culture solutions such as skim milk powder and whey degradation products. Milk includes those before sterilization and those after sterilization.
- raw milk Specific ingredients (materials) of raw milk include water, raw milk, pasteurized milk, skim milk, whole milk powder, skim milk powder, whole fat concentrated milk, skim concentrated milk, butter milk, butter, cream, etc. Also good. Further, whey protein concentrate (WPC), whey protein isolate (WPI), ⁇ -lactalbumin ( ⁇ -La), ⁇ -lactoglobulin ( ⁇ -Lg) and the like may be included.
- WPC whey protein concentrate
- WPI whey protein isolate
- ⁇ -La ⁇ -lactalbumin
- ⁇ -Lg ⁇ -lactoglobulin
- the method for producing fermented milk includes a raw material mix preparation step in which raw materials are mixed (prepared). What is necessary is just to employ
- a medium usually used can be used as a medium for culturing lactic acid bacteria and the like. That is, any medium can be used as long as it contains a nitrogen source, inorganic substances and other nutrients in addition to the main carbon source.
- the carbon source lactose, glucose, sucrose, fructose, starch hydrolyzate, waste molasses and the like can be used according to the assimilation ability of the bacteria used.
- the nitrogen source organic nitrogen-containing substances such as casein hydrolyzate, whey protein hydrolyzate, ⁇ -lactalbumin, ⁇ -lactoglobulin, glycomacropeptide, and soy protein hydrolyzate can be used.
- the growth promoter meat extract, fish extract, yeast extract and the like can be used as the growth promoter.
- an anaerobic state is preferable, but a microaerobic state by liquid stationary culture ordinarily used may be used.
- a known method such as a method of culturing in a carbon gas gas layer can be applied, but other methods may be used.
- the culture temperature is preferably 30 to 47 ° C, more preferably 35 to 46 ° C, and still more preferably 37 ° C to 45 ° C.
- the pH of the medium in which lactic acid bacteria and the like are cultured is preferably maintained at 6 to 7, but other pH conditions may be used as long as the temperature allows the bacteria to grow.
- the culture time for lactic acid bacteria and the like is usually preferably 1 to 48 hours, more preferably 8 to 36 hours, still more preferably 10 to 24 hours.
- the solid content of non-fat milk is 8% by weight or more, and the number of lactic acid bacteria or the number of yeasts is 10 million / ml or more. For example, it is 10 11 pieces / ml or less.
- the fermented product and / or culture of lactic acid bacteria and / or bifidobacteria which are active ingredients of the present invention, have sphingolipid absorption promoting activity (Examples 1 and 2 to be described later), and usually ceramide absorption promoting activity. Also have. Therefore, the use of the sphingolipid absorption promoter of the present invention can improve the absorption of the sphingolipid in the living body, and thus various effects exhibited by the presence of the sphingolipid or its derivative in the living body. Can be further improved.
- sphingolipid is sphingomyelin
- sphingomyelin absorption promoter of the present invention it is possible to improve the absorption of sphingomyelin in vivo, Various actions exhibited by the presence of sphingomyelin or a derivative thereof in a living body can be further improved.
- the sphingolipid is ceramide, glycosyl ceramide, or galactosyl ceramide
- the ceramide, glycosyl ceramide, or galactosyl ceramide absorption enhancer of the present invention by using the ceramide, glycosyl ceramide, or galactosyl ceramide absorption enhancer of the present invention, in vivo ceramide, glycosyl ceramide, or Absorption of galactosylceramide can be improved. For this reason, various actions exhibited by the presence of ceramide, glycosylceramide, or galactosylceramide and their derivatives in vivo can be further improved.
- Deterioration of skin condition due to increased presence of sphingomyelin or its inducer in the body (decreased skin barrier function, dry skin and skin, decreased moisture content of stratum corneum, atopic dermatitis, etc. ) Can be improved, improved, enhanced, and improved in preventive effect.
- visceral fat accumulation suppression and blood adiponectin concentration increase promoting action (anti-hyperglycemic action, anti-hyperlipidemic action) (JP 2007) -320900), infectious disease prevention action (Japanese Patent Laid-Open No. 2008-037788), and the like.
- the skin barrier function can be further improved in the state where the skin barrier function is lowered by ultraviolet rays.
- the deterioration of the skin condition includes, for example, a reduction in skin barrier function, skin drying, skin roughness, a decrease in the amount of water in the stratum corneum, and atopic dermatitis.
- Reduction of the barrier function of the skin includes maintenance of the barrier function.
- the reduction in the skin barrier function is preferably a reduction in the skin barrier function under the irradiation of ultraviolet rays.
- prevention, suppression or improvement of an exacerbated state is used in a sense encompassing adjustment, delay of progression, mitigation, prevention of onset, prevention of recurrence, etc. of such a state.
- the present invention it is possible to increase the amount of sphingolipid absorbed in the living body by promoting the absorption of the sphingolipid, and as a result, the in vivo action (function) induced by the absorption of the sphingolipid into the living body. , Efficacy) can be improved, improved and enhanced.
- the in vivo action referred to here is induced by absorption of sphingolipid into the living body, and specifically has various effects as described above. Therefore, according to the present invention, it is also possible to provide an enhancer of an action (function) in vivo induced by absorption of sphingolipid (an enhancer of function accompanying absorption (ingestion) of sphingolipid).
- composition for Oral Intake or Enteral Administration As described above, according to the present invention, the active ingredient of the present invention, that is, a fermented and / or cultured product of lactic acid bacteria and / or bifidobacteria, and a sphingolipid.
- a composition for oral ingestion or enteral administration is provided. It can also be said that this composition comprises the sphingolipid absorption promoter of the present invention as such an active ingredient.
- Lactic acid bacteria and / or bifidobacteria fermentations and / or cultures often already contain sphingolipids themselves, but in a preferred embodiment of the invention the composition of the invention comprises lactic acid bacteria and And / or bifidobacteria fermentation and / or culture and additional sphingolipids.
- the composition of the present invention can be distinguished from a fermentation product and / or culture product of lactic acid bacteria and / or bifidobacteria such as conventional yogurt.
- additional sphingolipid refers to a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria when a sphingolipid is contained in the fermented product and / or culture of lactic acid bacteria and / or bifidobacteria. It means a sphingolipid that is additionally present in the composition beyond the amount of the sphingolipid itself contained in the product.
- the sphingolipid itself may be used as it is, and examples thereof include a high content phospholipid concentrate (MPL) of milk-derived sphingomyelin. It can also be obtained as an insoluble fraction of acetone (solvent) and / or ethanol from cream or butter or from butter ram which is a by-product in producing butter oil.
- MPL high content phospholipid concentrate
- Bataselam is also used in the city milk field and is available (for example, manufactured by Tatua, New Zealand). Bataselam is rich in MFGM in which sphingomyelin is localized, and is suitable as a raw material.
- the total lipid was extracted from chicken skin powder, and the dried total lipid was dried and extracted with a mixed solvent of an aliphatic hydrocarbon solvent and a water-soluble ketone solvent, and an insoluble portion mainly composed of sphingomyelin was removed.
- a method for extracting sphingomyelin by extraction with a mixed solvent of water and a water-soluble ketone solvent and removing non-lipid components contained in the soluble part Existing methods such as extraction methods from seafood and animal birds can be used. From the viewpoint of flavor, milk-derived sphingomyelin is preferred.
- fermented products and / or cultures of lactic acid bacteria and / or bifidobacteria are set type yogurt (solid fermented milk), soft type yogurt (pasted fermented milk), drink yogurt (liquid fermented milk).
- Various forms of yogurt such as cereals, fruits, vegetables, and nutrient ingredients may also be used.
- composition for oral ingestion or enteral administration of the present invention is preferably one in which the absorption of sphingolipids into the living body is enhanced, more preferably the absorption of sphingomyelin into the living body is enhanced. It is a thing. That is, the composition for oral ingestion or enteral administration of the present invention can be referred to as a “sphingolipid superabsorbent”, preferably a “sphingomyelin superabsorbent” composition for oral ingestion or enteral administration.
- a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria, and sphingo is preferably 1 to 10000 mg, more preferably 5 to 5000 mg of lactic acid bacteria and / or bifidobacteria fermentation and / or culture (dry weight (powder)) per 1 mg of sphingolipid. More preferably, it is contained in an amount of 10 to 750 mg.
- the fermented product and / or culture of lactic acid bacteria and / or bifidobacteria in the composition for oral consumption or enteral administration of the present invention And the ratio of sphingolipid to 1 mg of sphingolipid, preferably 0.01 to 100 g, more preferably 0.05 to lactic acid bacteria and / or bifidobacteria fermented product and / or culture (wet weight). To 50 g, more preferably 0.1 to 7.5 g.
- composition for oral ingestion or enteral administration of the present invention is preferably used for in vivo action induced by absorption of sphingomyelin into the living body.
- the composition for oral ingestion or enteral administration according to the present invention is more preferably such that the action in the living body is prevention or improvement of skin condition deterioration, cancer suppression action, skin beautification, infant brain development promotion. It is used for an action selected from the group consisting of an action, an action to improve mitochondrial function, an action to improve motor function, an action to suppress visceral fat accumulation and an increase in blood adiponectin concentration, and an action to prevent infection.
- the composition for oral intake or enteral administration of the present invention is preferably used for preventing, suppressing or improving the deterioration of the skin condition.
- the deterioration of the skin condition is preferably a deterioration of the barrier function of the skin.
- the deterioration of the barrier function of the skin is due to the irradiation of ultraviolet rays.
- the composition of this invention can be a pharmaceutical composition as one preferable aspect.
- the pharmaceutical composition is prepared as an oral preparation or a parenteral preparation according to a conventional method using additives that are acceptable for formulation. From the viewpoint of simplicity, an oral preparation is preferable.
- oral preparations take the form of solid preparations such as tablets, powders, fine granules, granules, capsules, pills, sustained-release preparations, and liquid preparations such as solutions, suspensions, and emulsions. Can do.
- Additives that are acceptable for formulation include, for example, excipients, stabilizers, preservatives, wetting agents, emulsifiers, lubricants, sweeteners, colorants, fragrances, buffers, antioxidants, pH Examples thereof include regulators.
- a food or drink comprising the sphingolipid absorption promoter of the present invention or the composition for oral intake or enteral administration described above.
- compositions and food / beverage products of this invention are manufactured by the manufacturing method which comprises adding the absorption promoter of this invention, or its active ingredient to the composition and the material component of food / beverage products, for example. Can do.
- Arbitrary ingredients can be added to the food and drink of the present invention as required.
- optional components that can be added there are no particular restrictions, but usually ingredients to be blended in foods and drinks, sweeteners, acidulants, vegetable and fruit juices and their extracts, vitamins, minerals, Nutrients such as amino acids, useful microorganisms such as lactic acid bacteria, bifidobacteria and propionic acid bacteria and their cultures, functional sugars such as oligosaccharides, royal jelly, collagen, ceramide, glucosamine, astaxanthin and polyphenols
- filler, a sour agent, a coloring agent, an emulsifier, a preservative, etc. can be mix
- the food and drink are other than the pharmaceutical composition and are not particularly limited as long as they are ingestible forms such as solutions, suspensions, emulsions, powders, and solid molded products.
- dairy products such as milk drinks, yogurts, lactic acid bacteria drinks, fermented milk, ice creams, creams, cheeses; soft drinks, fruit juice drinks, vegetable drinks, soy milk drinks, coffee drinks, tea drinks Jelly drinks, cocoa, smoothie powdered drinks and sports powdered drinks, nutrition-enriched powdered drinks, cosmetic powdered foods, powdered soup, steamed bread, concentrated drinks, alcoholic drinks, etc .
- bread, pasta , Flour products such as noodles, cake mix, fried flour, bread crumbs
- confectionery such as chocolate, gum, candy, cookies, gummi, snacks, Japanese confectionery, jelly, pudding, etc .
- the food and drink are milk drinks (which may include processed milk), fermented milk, soft drinks, jelly drinks, tablets, cosmetic powdered foods, powdered drinks, liquid foods, liquids.
- the food and drink is a milk beverage, fermented milk, soft drink, jelly beverage, prepared milk powder tablet, cosmetic powdered food, and according to a more preferred embodiment, the food and drink The product is a milk beverage (which may include processed milk), fermented milk.
- the food or drink is a functional food, a health nutrition food, a supplement, a food for specified health use, a functional display food, or a food with a disease risk reduction display.
- the indication of disease risk reduction is the indication of food and drink that may reduce the disease risk, and is based on the standards established by the FAO / WHO Joint Food Standards Committee (Codex Committee). , Or with reference to the standard, it can be a defined or recognized display.
- the food and drink of the present invention are, for example, foods suitable for consumers who expect improvement or alleviation of skin condition deterioration, foods suitable for improvement of skin condition deterioration, that is, so-called foods for specific health use or functions It can be provided as a sex indication food.
- the content of sphingomyelin in the food and drink and the composition within a predetermined range.
- the specific content can be changed depending on the type and form of the food or drink or the composition, the purpose of prevention / improvement, etc., and thus it is difficult to define it uniformly, but in the composition of the present invention, the adult ( (Weight: 60 kg) per day, milk-derived sphingomyelin can be adjusted to an effective amount that can be ingested at 0.5 to 1500 mg, preferably 1 to 1000 mg, more preferably 5 to 500 mg.
- the content of sphingolipid for example, sphingomyelin, can be measured by a conventional method, but may be measured, for example, according to the description in Examples 1 and 2 described later. Moreover, for example, it can measure using liquid chromatography and using AQUASIL SP100 (4.6X250mm, Senshu Scientific Co., Ltd.) as a column.
- the mobile phase for example, a solution in which 0.5 mM phosphate-citrate buffer (pH: 3.0) and methanol are mixed at a ratio of 5 to 95 may be used.
- the measurement time can be set to 20 minutes
- the flow rate of the mobile phase can be set to 0.6 mL / min
- the column temperature can be set to 40 ° C.
- the absorbance can be detected at 205 nm.
- sphingomyelin derived from milk, Nagara Science Co., Ltd.
- it can be quantified by the area ratio.
- the content of the active ingredient in foods and drinks and compositions can be defined per packaging form.
- the content of sphingolipids is preferably 5 to 1500 mg. 6 to 1000 mg, more preferably 7 to 500 mg, and in the case of a composition, the content of sphingolipid is 0.5 to 1500 mg, preferably 1 to 1000 mg, more preferably 5 to 500 mg. be able to.
- the amount (content) per packaging form is not limited to a single intake, and may include intakes for multiple doses or multiple days (for example, for 30 days).
- the content of sphingolipid is 5 to 45000 mg, preferably 6 to 30000 mg, more preferably 7 to 15000 mg.
- the content of sphingolipid is 0.5 to 45000 mg, preferably 1 It can be contained in an amount of ⁇ 30000 mg, more preferably 5 to 15000 mg.
- the conventional general milk drink and fermented milk contain 20 mg of phospholipid per gram of lipid, whereas the milk drink and fermented milk of the present invention contain 25 to 3000 mg of phospholipid per gram of lipid. , Preferably 30 to 2500 mg, more preferably 40 to 2000 mg, and still more preferably 50 to 1500 mg.
- the conventional general milk drink and fermented milk contain 6 mg of sphingomyelin per gram of lipid, but the food or drink or composition of the present invention contains 7 to 1500 mg of sphingomyelin per gram of lipid. Contained, preferably 8 to 1250 mg, more preferably 9 to 1000 mg, and still more preferably 10 to 750 mg. That is, in one preferred embodiment of the present invention, those having an intentionally increased sphingomyelin content are used.
- phospholipid is contained at 1 to 300 mg / g, preferably 1.5 to 250 mg / g. More preferably 2 to 200 mg / g, still more preferably 2.5 to 150 mg / g.
- sphingomyelin is contained at 0.2 to 60 mg / g, preferably 0.25 to 50 mg / g, more preferably 0.3. It can be contained at -40 mg / g, more preferably 0.35-30 mg / g.
- the conventional general milk drink and fermented milk contain 20 mg of phospholipid per gram of lipid, but the milk drink and fermented milk of the present invention contain 25 to 3000 mg of phospholipid per 1 g of lipid. It is preferably contained in an amount of 30 to 2500 mg, more preferably 40 to 2000 mg, and still more preferably 50 to 1500 mg.
- sphingomyelin is contained at 0.05 to 60 mg / g, preferably 0.1 to 50 mg / g, more preferably 0.15 to It can be contained at 40 mg / g, more preferably 0.2 to 30 mg / g.
- the conventional general milk drink and fermented milk contain 20 mg of phospholipid per gram of lipid, but the milk drink and fermented milk of the present invention contain 25 to 3000 mg of phospholipid per 1 g of lipid. It is preferably contained in an amount of 30 to 2500 mg, more preferably 40 to 2000 mg, and still more preferably 50 to 1500 mg.
- sphingomyelin when containing almost no lipid (non-fat), is contained at 0.02 to 60 mg / g.
- it can be contained at 0.04 to 50 mg / g, more preferably 0.06 to 40 mg / g, and still more preferably 0.08 to 30 mg / g.
- a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria is orally administered or enterally administered to a subject who wants to take the sphingolipid simultaneously with the sphingolipid.
- a method for promoting the absorption of sphingolipids is preferably, the sphingolipid is sphingomyelin.
- a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria is orally administered or enterally administered to a subject who wants to take sphingolipids simultaneously with sphingolipids.
- a method for promoting absorption of ceramide is provided.
- the above method excludes medical use.
- the subject is preferably a human or a non-human mammal.
- the method is preferably used for a subject in whom intake of sphingolipid is desired, wherein a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria are continuously orally ingested for 2 days or more, or enterally administered. Therefore, it is possible to provide a method for promoting absorption of sphingolipids and a method for promoting absorption of ceramides for subjects in whom intake of sphingolipids is desired.
- Example 1 Evaluation test of absorbability of sphingomyelin in simultaneous administration of yogurt and sphingomyelin To rats, only milk-derived sphingomyelin is administered, or powdered yogurt and milk-derived sphingomyelin are administered simultaneously, lymph The amount of sphingomyelin absorbed was evaluated.
- test solution (A), (B) and (C) as will be described later, the rats are divided into 3 groups (a, b, c), and these test solutions are administered into the stomach. From 1 hour before, lymph fluid was collected in Spitz tubes treated with EDTA for 3 groups (a, b, c).
- each test solution (A), (B), and (C) was sent into the stomach in 1 minute using a syringe pump (flow rate: 3 mL / min), and then the syringe pump was used.
- the buffer solution was fed into the stomach in 6 hours (flow rate: 3 mL / min).
- lymph fluid was collected in Spitz tubes treated with EDTA for three groups (a, b, c).
- Test Solution Each test solution (A), (B) and (C) was prepared as follows.
- Triolein 195 mg, bovine serum albumin: 50 mg, and sodium taurocholate: 200 mg were mixed with milk-derived sphingomyelin (SM, purity 98%, Nagara Science Co., Ltd.): 5 mg ultrasonically emulsified. It was.
- SM milk-derived sphingomyelin
- Triolein 192 mg, bovine serum albumin: 50 mg, and sodium taurocholate 200 mg were mixed with milk-derived sphingomyelin (SM, purity 98%, Nagara Science): 4.75 mg was emulsified with ultrasound. I let you. Along with this, 250 mg of powdered yogurt (YG, fat: about 0%, Meiji Bulgaria yogurt fat, obtained from Meiji Co., Ltd.) was prepared.
- SM milk-derived sphingomyelin
- ceramide (d18: 1-C16: 0, obtained from Avanti Polar Lipids) and sphingomyelin (d18: 1-C16: 0 SM, obtained from Avanti Polar Lipids) were used. Using these standard products as equivalents, ceramide (d16: 1-C16: 0), sphingomyelin (d16: 1-C16: 0 SM) using LC / MS / MS (ACQUITY premier XE (Waters)) was quantified.
- mobile phase A was started from 100%, and after 30 minutes, mobile phase B was gradiented to 100%, then mobile phase B was made 100% and held for 2 minutes, and after another 3 minutes, The mobile phase A was switched to 100%.
- the measurement time of one sample in LC / MS / MS is set to 35 minutes
- the flow rate of the mobile phase is set to 0.4 mL / min
- the temperature of the column is set to 40 ° C.
- electrospray ionization is used. Detected with.
- capillary voltage is 3000V
- source temperature is 120 ° C
- solvent removal temperature is 400 ° C
- solvent removal gas flow rate is 850L / hour
- cone gas flow rate is 50L / hour
- cone The voltage was set at 40V / hour.
- FIG. 1 shows the transition of the amount of ceramide molecular species (d16: 1-C16: 0).
- the ceramide molecular species amount was higher in the SM + YG group than in the SM group.
- FIG. 2 shows changes in the amount of sphingomyelin molecular species (d16: 1-C16: 0 SM).
- 3, 4, 5, and 6 hours after oral administration of each test solution the amount of sphingomyelin molecular species was higher in the SM + YG group than in the SM group.
- Example 2 Evaluation test of absorbability of sphingomyelin in simultaneous intake of yogurt and milk-derived sphingomyelin-rich phospholipid concentrate (MPL) Oral administration of MPL alone or oral administration of yogurt and MPL simultaneously to rats Thus, the amount of ceramide in the blood was evaluated.
- MPL milk-derived sphingomyelin-rich phospholipid concentrate
- MPL Group Test Solution
- D MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
- E MPL + YG group: Test solution
- E Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight was administered.
- ceramide (d18: 1-C16: 0, d18: 1-C22: 0, d18: 1-C23: 0, d18: 1-C24: 0, obtained from Avanti Polar Lipids) was used. Using these standard products as equivalents, LC / MS / MS (ACQUITY premier XE (manufactured by Waters)) was used and ceramide (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0).
- mobile phase A was started from 100%, and after 30 minutes, mobile phase B was gradiented to 100%, then mobile phase B was made 100% and held for 2 minutes, and after another 3 minutes, The mobile phase A was switched to 100%.
- the measurement time of one sample in LC / MS / MS is set to 35 minutes
- the flow rate of the mobile phase is set to 0.4 mL / min
- the temperature of the column is set to 40 ° C.
- electrospray ionization is used. Detected with.
- capillary voltage is 3000V
- source temperature is 120 ° C
- solvent removal temperature is 400 ° C
- solvent removal gas flow rate is 850L / hour
- cone gas flow rate is 50L / hour
- cone The voltage was set at 40V / hour.
- FIG. 3 shows changes in serum ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0).
- ceramide molecular species (d16: 1-C16: 0) 90 and 180 minutes after administration of the test solution, and for ceramide molecular species (d16: 1-C22: 0, d16: 1-C23: 0), At 90, 180, and 270 minutes after administration, ceramide molecular species (d16: 1-C24: 0) were significantly more significant in the MPL + YG group than in the MLP group at 90, 180, 270, and 360 minutes after administration of the test solution. It was overpriced.
- FIG. 4 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species were significantly higher in the MPL + YG group in the area under the time curve than in the MPL group.
- Example 3 Effect of yogurt and sphingolipid on deterioration of skin barrier function under irradiation of ultraviolet rays
- Hairless mice whose skin barrier function was deteriorated by irradiation with ultraviolet rays were treated with sphingomyelin or sphingomyelin and yogurt. It was orally ingested for 3 days, and the influence on the skin barrier function (the amount of stratum corneum moisture, the amount of transdermal moisture transpiration (TEWL)) was evaluated.
- sphingolipid milk-derived sphingomyelin (SM, purity 98%, Nagara Science) was used.
- Control group group in which normal feed is ingested
- SM group group in which sphingomyelin is orally administered at 10 mg / kg / day
- SM + YG group sphingomyelin and yoghurt in 10 mg / kg / day, 11.3 g / kg /
- a group to be orally administered on day (however, in the SM group and SM + YG group, collagen is further orally administered at a rate of 1000 mg / kg / day in addition to sphingomyelin and yogurt).
- Transdermal moisture transpiration (TEWL) Transcutaneous moisture transpiration (TEWL) was measured with a tevameter (Tewemeter MPA580, Curage and Khazaka Electronic GmbH) using a probe kept at 29 ° C. for 20 seconds. About the obtained measurement result, the average of 3 times was employ
- TEWL Transdermal moisture transpiration
- Example 4 Evaluation test of absorption of sphingomyelin in simultaneous intake of unfermented milk and MPL When rats were orally administered with MPL alone, when yogurt and MPL were orally administered simultaneously, and with unfermented milk and MPL The amount of ceramide in the blood was evaluated for each case of simultaneous oral administration.
- Rats SD strain, male, body weight: about 270 g
- test solutions F), (G) and (H) shown below were orally administered.
- blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after administration, and serum was obtained according to a conventional method.
- MPL group Test solution (F): MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
- MPL + YG group Test solution (G): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight was administered.
- FIG. 7 shows the area under the time curve of the amount of ceramide molecular species in serum.
- the area under the time curve was significantly higher in the order of the MPL group, the MPL + unfermented milk group, and the MPL + YG group in comparison with the MPL group.
- Absorption of sphingomyelin is promoted by simultaneous ingestion of milk-derived phospholipid concentrate and non-fermented milk at a high content of sphingomyelin, but milk-derived phospholipid concentrate at a high content of sphingomyelin It was found that the simultaneous intake of yogurt and yogurt further promotes the absorption of sphingomyelin.
- Example 5 Evaluation test of absorption of sphingomyelin in simultaneous intake of yogurt fraction and MPL When rats were orally administered with MPL alone, yogurt and MPL were orally administered simultaneously, yogurt fraction supernatant and The amount of ceramide in blood was evaluated when MPL was orally administered at the same time and when yogurt fraction precipitate and MPL were orally administered at the same time.
- Rats SD strain, male, body weight: about 270 g
- test solutions I), (J), (K) and (L) shown below were orally administered.
- blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after administration, and serum was obtained according to a conventional method.
- MPL Group Test Solution (I): MPL: 540 mg (100 mg as sphingomyelin) was administered per 1 kg of body weight.
- MPL + YG group Test solution (J): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight Was administered.
- K MPL + YG supernatant group: Test solution (J): Yogurt supernatant: 743 mg and MPL: 539 mg (100 mg as the total amount of sphingomyelin) were administered per kg of body weight.
- MPL + YG precipitation group Test solution (K): Yogurt precipitation: 455 mg and MPL: 536 mg (100 mg as the total amount of sphingomyelin) were administered per 1 kg of body weight.
- FIG. 8 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species had significantly higher areas under the time curve in the MPL + YG group and MPL + YG supernatant group than in the MPL group, but there was a significant difference between the MPL group and the MPL + YG precipitation group. There wasn't.
- Example 6 Evaluation test of absorption of sphingomyelin in simultaneous intake of lactic acid and MPL When MPL alone was orally administered to rats, yogurt and MPL were orally administered simultaneously, and lactic acid and MPL were orally administered simultaneously For each of these, the amount of ceramide in the blood was evaluated.
- Rats SD strain, male, body weight: about 270 g
- test solutions L), (M) and (N) shown below were orally administered.
- blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after administration, and serum was obtained according to a conventional method.
- MPL Group Test solution (L): MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
- MPL + YG group Test solution (M): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight was administered.
- N MPL + lactic acid group: Test solution (N): Lactic acid (obtained from Wako Pure Chemical Industries, Ltd.) per kg of body weight: 109 mg (the amount of lactic acid in yogurt was equal to the pH), and MPL: 540 mg (sphingo A dose of 100 mg) was administered as myelin.
- FIG. 9 shows the area under the time curve of the amount of ceramide molecular species in serum.
- the area under the time curve was significantly higher in the MPL + YG group than in the MPL group, but no significant difference was observed between the MPL group and the MPL + lactic acid group.
- Example 7 Evaluation test of absorption of sphingomyelin in simultaneous intake of whey protein and MPL When rats were orally administered MPL alone, yogurt and MPL were orally administered simultaneously, and whey protein and MPL were orally administered simultaneously In each case, the amount of ceramide in the blood was evaluated.
- Rats SD strain, male, body weight: about 270 g
- test solutions O), (P) and (Q) shown below were orally administered.
- blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after administration, and serum was obtained according to a conventional method.
- MPL Group Test Solution
- O MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
- MPL + YG group Test solution
- P Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight was administered.
- FIG. 10 shows the area under the time curve of the amount of ceramide molecular species in serum.
- the area under the time curve was significantly higher in the MPL + YG group than in the MPL group, but there was no significant difference between the MPL group and the MPL + whey protein group.
- Example 8 Evaluation Test of Sphingomyelin Absorption by Simultaneous Intake of Polysaccharide and MPL When rats are orally administered with MPL alone, yogurt and MPL are orally administered simultaneously, and polysaccharide and MPL are orally administered simultaneously In each case, the amount of ceramide in the blood was evaluated.
- Rats SD strain, male, body weight: about 270 g
- Rats were acclimated and bred in one week. Then, after the rats were fasted for 16 hours, they were divided into 3 groups, and the test solutions (R), (S) and (T) shown below were orally administered. Subsequently, blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after the administration, and serum was obtained according to a conventional method.
- MPL group Test solution (R): MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
- S MPL + YG group: Test solution (S): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as the total amount of sphingomyelin) per kg of body weight was administered.
- T MPL + polysaccharide group: Test solution (T): administration of polysaccharide: 52.5 mg (equal to polysaccharide in yogurt) and MPL: 540 mg (100 mg as sphingomyelin) per kg body weight did.
- FIG. 11 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species were significantly higher in the area under the time curve in the MPL + YG group and the MPL + polysaccharide group than in the MPL group.
- Example 9 Evaluation test of absorption of sphingomyelin in simultaneous intake of yogurt and MPL prepared by lactic acid bacteria and / or bifidobacteria When MPL alone was orally administered to rats, it was prepared by lactic acid bacteria and / or bifidobacteria The amount of ceramide in blood was evaluated for each of the cases where yogurt and MPL were orally administered simultaneously.
- Rats SD strain, male, body weight: about 270 g
- Rats were acclimated and bred in one week. Then, after the rats were fasted for 16 hours, the rats were divided into 3 groups, and the test solutions (U), (V), (W), (X) and (Y) shown below were orally administered. Subsequently, blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after the administration, and serum was obtained according to a conventional method.
- MPL Group Test Solution (U): MPL: 540 mg (100 mg as sphingomyelin) was administered per 1 kg of body weight.
- V MPL + YG (1) group: Test solution (V): Yogurt per kg of body weight (1) (prepared by lactic acid bacteria Lactobacillus Gasseri and Streptococcus thermophilus, Meiji Probio Yogurt LG21 Fat Zero, obtained from Meiji Co., Ltd.): A dose of 3 g and MPL: 535 mg (100 mg as the total amount of sphingomyelin) was administered.
- (Y) MPL + YG (4) group Test solution (Y): Yogurt per kg of body weight (4) (prepared by Bifidobacterium longum, bihidas BB536 plain yogurt fat zero, obtained from Morinaga Milk Industry Co., Ltd.): 11.3 g , And MPL: 535 mg (100 mg total sphingomyelin) was administered.
- FIG. 12 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species had significantly higher areas in the MPL + YG (1) group, the MPL + YG (2) group, the MPL + YG (3) group, and the MPL + YG (4) group as compared to the MPL group.
- Example 10 Evaluation test of absorption of glucosylceramide in simultaneous intake of yogurt and glucosylceramide When glucosylceramide (GC) alone was orally administered to a rat, each of cases where yogurt and glucosylceramide L were orally administered simultaneously, The amount of ceramide in the blood was evaluated.
- glucosylceramide GC
- GC Group Test Solution
- Y A dose of GC: 1613 mg (100 mg as glucosylceramide, obtained from Nipunceramide RPS, Nippon Flour) was administered per kg of body weight.
- Z GC + YG group: Test solution (Z): A dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and GC: 1613 mg per kg of body weight was administered.
- FIG. 13 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species were significantly higher in the GC + YG group in terms of the area under the time curve than in the GC group.
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Abstract
Description
本願は、先行する日本国特許出願である特願2015-000745号(出願日:2015年1月6日)に基づくものであって、その優先権の利益を主張するものであり、その開示内容全体は参照することによりここに組み込まれる。 This application is based on Japanese Patent Application No. 2015-000745 (filing date: January 6, 2015), which is a prior Japanese patent application, and claims the benefit of its priority. The entirety is hereby incorporated by reference.
本発明は、スフィンゴ脂質吸収促進剤(Absorption Promoter of Sphingolipid)に関する。また、本発明は、乳酸菌および/またはビフィズス菌の発酵物および/または培養物と、追加のスフィンゴ脂質とを含んでなる、経口摂取用または経腸投与用組成物に関する。 The present invention relates to a sphingolipid absorption promoter (Absorption Promoter of Sphingolipid). The present invention also relates to a composition for oral ingestion or enteral administration comprising a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria and an additional sphingolipid.
スフィンゴ脂質は、真核生物の細胞膜を構成する成分であり、スフィンゴイド塩基を持つ脂質の総称であり、経口摂取に基づく、皮膚のバリア機能の改善効果などが明らかにされている。 Sphingolipid is a component that constitutes eukaryotic cell membranes, and is a generic name for lipids having sphingoid bases. It has been clarified that the effect of improving the barrier function of the skin based on oral ingestion.
スフィンゴミエリンは、乳由来のスフィンゴ脂質の一つである。スフィンゴミエリンについては、経口摂取に基づく、皮膚の状態の悪化(皮膚のバリア機能の低下、皮膚の乾燥・かさつき、角層の水分量の低下、アトピー性皮膚炎など)の予防効果や改善効果などが明らかにされている。 Sphingomyelin is one of milk-derived sphingolipids. For sphingomyelin, preventive and improving effects on skin conditions (decrease in skin barrier function, dryness and roughness of skin, decrease in water content of stratum corneum, atopic dermatitis, etc.) based on ingestion Etc. have been revealed.
さらに、スフィンゴミエリンについては、ガン(大腸がん)抑制作用(菅原達也、「食品機能性成分としてのスフィンゴ脂質の消化と吸収」、日本栄養・食糧学会誌、第66巻4号、pp.177-183 (2013))、美肌作用(特開2008-184428号公報)、乳幼児脳発達促進作用(特許第3203485号)、ミトコンドリア機能向上作用(特開2011-157329号公報)、運動機能向上作用(特開2014-141496号公報)、内臓脂肪蓄積抑制および血中アディポネクチン濃度上昇促進作用(抗高血糖作用、抗高脂血症作用)(特開2007-320900号公報)、感染症予防作用(特開2008-037788号公報)などがあることが知られている。 Furthermore, about sphingomyelin, cancer (colon cancer) inhibitory action (Tatsuya Sugawara, “Digestion and absorption of sphingolipid as a functional food ingredient”, Journal of Japanese Society of Nutrition and Food, Vol. 66, No. 4, pp.177 -183 (2013)), skin beautification (Japanese Patent Laid-Open No. 2008-184428), infant brain development promoting action (Patent No. 3203485), mitochondrial function improving action (Japanese Patent Laid-Open No. 2011-157329), motor function improving action ( JP-A-2014-14196), visceral fat accumulation suppression and blood adiponectin concentration increase promoting action (anti-hyperglycemic action, anti-hyperlipidemic action) (JP-A 2007-320900), infectious disease preventing action (special No. 2008-037788) is known.
スフィンゴミエリンは、セラミドとホスホコリンで構成される物質であり、スフィンゴミエリナーゼによって、セラミドとホスホコリンとに加水分解される。さらに、セラミドは、セラミダーゼによって、スフィンゴイド塩基と脂肪酸とに加水分解され、その多くは、脂肪酸として、小腸の上皮細胞に吸収されると共に、一部のスフィンゴイド塩基は、スフィンゴミエリンやセラミドなどに再合成される。なお、スフィンゴミエリンは、腸内細菌によって分解されることが示唆されている。 Sphingomyelin is a substance composed of ceramide and phosphocholine and is hydrolyzed to ceramide and phosphocholine by sphingomyelinase. Furthermore, ceramide is hydrolyzed by ceramidase into sphingoid bases and fatty acids, many of which are absorbed as fatty acids by epithelial cells of the small intestine, and some sphingoid bases are converted into sphingomyelin, ceramide, etc. Recombined. It has been suggested that sphingomyelin is degraded by enteric bacteria.
グルコシルセラミドは、スフィンゴ塩基と脂肪酸からなるセラミドにグルコースが結合された物質である。グルコセラミド分解酵素によって、セラミドとグルコースに加水分解される。ガラクトシルセラミドは、スフィンゴ塩基と脂肪酸からなるセラミドにガラクトースが結合された物質である。 Glucosylceramide is a substance in which glucose is bound to ceramide composed of sphingo base and fatty acid. It is hydrolyzed to ceramide and glucose by glucoceramide-degrading enzyme. Galactosylceramide is a substance in which galactose is bound to ceramide composed of a sphingo base and a fatty acid.
一般的に、脂質を経口摂取すると、胆汁酸によって、乳化され、リパーゼによって、脂肪酸とモノグリセリドへ分解されて、小腸で吸収される。さらに、モノグリセリドは、小腸の上皮細胞内で、トリアシルグリセロールに再合成され、カイロミクロンとなって、リンパ管に送られて、胸管を経てから、全身循環へと移行する。 Generally, when lipids are taken orally, they are emulsified by bile acids, decomposed into fatty acids and monoglycerides by lipase, and absorbed in the small intestine. Furthermore, monoglycerides are re-synthesized into triacylglycerol in the epithelial cells of the small intestine, converted into chylomicrons, sent to the lymphatic vessels, pass through the thoracic duct, and then enter the systemic circulation.
ところが、スフィンゴミエリンやセラミドは、その消化・吸収性が低いことが明らかになっている。その原因として、消化管内のスフィンゴミエリナーゼの活性が低いことや、そこに発現したトランスポーターによって、いったん吸収したスフィンゴイド塩基が排出されることなどが考えられている。 However, it has been clarified that sphingomyelin and ceramide have low digestibility and absorption. Possible causes include the low activity of sphingomyelinase in the gastrointestinal tract and the elimination of sphingoid bases once absorbed by the transporter expressed there.
したがって、上記のような様々な作用が期待されるスフィンゴミエリンを含むスフィンゴ脂質を経口摂取した場合に、スフィンゴ脂質の吸収性を高めることができ、かつ、安全で、簡便かつ効率的な摂取手段が望まれていた。 Therefore, when a sphingolipid containing sphingomyelin, which is expected to have various effects as described above, is orally ingested, it is possible to increase the absorbability of the sphingolipid, and there is a safe, simple and efficient ingestion means. It was desired.
脂質の消化吸収を向上させることに関しては、例えば、特許第3920969号には、脂質の消化吸収を向上させるために、胆汁酸や胆汁酸塩を配合した栄養組成物が提案されている。しかしながら、ここには、スフィンゴ脂質について記載されておらず、また胆汁酸自体は苦みがあり、食品として使用する場合には、その影響を考慮しなければならない。 Regarding improving the digestion and absorption of lipids, for example, Patent No. 3920969 proposes a nutritional composition containing bile acids and bile salts in order to improve the digestion and absorption of lipids. However, it does not describe sphingolipids here, and bile acids themselves are bitter, and their effects must be taken into account when used as food.
発酵乳(ヨーグルト)は、乳に乳酸菌や酵母を混ぜて発酵することによって調製される発酵食品であり、その美味しさと、美容や健康面から幅広く食されている。 Fermented milk (yogurt) is a fermented food prepared by mixing lactic acid bacteria and yeast in milk and fermenting it, and is widely eaten from the viewpoint of its deliciousness, beauty and health.
例えば、特開平7-327633号公報には、キトサン、はと麦、粉末ヨーグルトを混合したキトサン加工食品が開示されている。ここで、粉末ヨーグルトは、キトサンの消化吸収を助ける働きがあることが記載されている。しかしながら、ここでの消化吸収機能は、粉末ヨーグルト中の活性レシチンの作用に着目したものであり、ここには、スフィンゴ脂質の消化吸収の促進については開示も示唆もされていない。 For example, Japanese Patent Application Laid-Open No. 7-327633 discloses a chitosan processed food in which chitosan, wheat and wheat yogurt are mixed. Here, it is described that powdered yogurt has a function of assisting in digestion and absorption of chitosan. However, the digestive absorption function here focuses on the action of active lecithin in powdered yogurt, and there is no disclosure or suggestion about the promotion of digestive absorption of sphingolipids.
本発明者らは今般、発酵乳(ヨーグルト)をスフィンゴミエリンと同時に摂取すると、スフィンゴミエリンの生体内への吸収量を増加させることができること、すなわち、スフィンゴミエリンの吸収が向上することを予想外にも見出した。このとき、本発明者らは、セラミドの吸収が向上することも見出している。そして、これらのことから、本発明者らは、乳酸菌および/またはビフィズス菌の発酵物および/または培養物の摂取によって、スフィンゴ脂質の吸収が促進できることを発見した。さらにスフィンゴミエリンを含むスフィンゴ脂質の生体内への吸収量が向上することで、スフィンゴ脂質の吸収に伴って期待される、皮膚のバリア機能の改善の他、様々な有益な作用や効果の向上を図ることができる。そして、本発明者らは、ヨーグルトと、ヨーグルトの含量を超えたスフィンゴミエリンとを含む経口用もしくは経腸用組成物を調製することで、スフィンゴミエリンの生体内への吸収量の向上を実際に確認した。本発明は、これら知見に基づくものである。 The present inventors have unexpectedly found that when fermented milk (yogurt) is ingested simultaneously with sphingomyelin, the amount of sphingomyelin absorbed can be increased, that is, the absorption of sphingomyelin is improved unexpectedly. I also found. At this time, the present inventors have also found that absorption of ceramide is improved. From these facts, the present inventors have found that absorption of sphingolipids can be promoted by ingestion of fermentation products and / or cultures of lactic acid bacteria and / or bifidobacteria. Furthermore, by improving the amount of sphingolipids, including sphingomyelin, absorbed in the body, the skin barrier function expected with the absorption of sphingolipids is improved, and various beneficial effects and effects are improved. Can be planned. And the present inventors actually improved the amount of sphingomyelin absorbed into the living body by preparing an oral or enteral composition containing yogurt and sphingomyelin exceeding the yogurt content. confirmed. The present invention is based on these findings.
よって、本発明は、スフィンゴ脂質を摂取した場合に、スフィンゴ脂質の吸収を向上や促進することができる手段であって、安全かつ簡便で、経済的(もしくは効率的)に吸収することができる手段を提供することを目的とする。 Therefore, the present invention is a means capable of improving or promoting the absorption of sphingolipids when ingesting sphingolipids, which is safe, simple and economical (or efficient). The purpose is to provide.
すなわち、本発明によれば、以下の発明が提供される。 That is, according to the present invention, the following inventions are provided.
<1> 乳酸菌および/またはビフィズス菌の発酵物および/または培養物を有効成分とする、スフィンゴ脂質吸収促進剤。 <1> A sphingolipid absorption promoter comprising as an active ingredient a fermentation product and / or culture product of lactic acid bacteria and / or bifidobacteria.
<2> 前記<1>のスフィンゴ脂質吸収促進剤において、スフィンゴ脂質がスフィンゴミエリンであり、スフィンゴミエリンの生体内への吸収を促進するのがよい。 <2> In the sphingolipid absorption promoter according to <1>, the sphingolipid is sphingomyelin, and it is preferable to promote absorption of the sphingomyelin into the living body.
<3> 前記<2>のスフィンゴ脂質吸収促進剤において、乳由来のスフィンゴミエリンの生体内への吸収を促進するのがよい。 <3> In the sphingolipid absorption promoter of <2>, it is preferable to promote absorption of milk-derived sphingomyelin into the living body.
<4> 前記<1>~<3>のいずれかのスフィンゴ脂質吸収促進剤において、スフィンゴ脂質がセラミド、グルコシルセラミド、ガラクトシルセラミドのいずれか1つ以上であるのがよい。 <4> In the sphingolipid absorption promoter according to any one of <1> to <3>, the sphingolipid may be any one or more of ceramide, glucosylceramide, and galactosylceramide.
<5> 前記<1>~<4>のいずれかのスフィンゴ脂質吸収促進剤において、乳酸菌および/またはビフィズス菌の発酵物および/または培養物が、乳酸菌および/またはビフィズス菌の乳発酵物および/または乳培養物であるのがよい。 <5> In the sphingolipid absorption promoter according to any one of <1> to <4>, the fermented product and / or culture product of lactic acid bacteria and / or bifidobacteria is a milk fermented product of lactic acid bacteria and / or bifidobacteria and / or Or it may be a milk culture.
<6> 多糖類を有効成分とする、スフィンゴ脂質吸収促進剤。 <6> A sphingolipid absorption promoter comprising a polysaccharide as an active ingredient.
<7> 前記<1>~<6>のいずれかのスフィンゴ脂質吸収促進剤と、スフィンゴ脂質とを含んでなる、経口摂取用または経腸投与用組成物。 <7> A composition for oral ingestion or enteral administration, comprising the sphingolipid absorption promoter according to any one of <1> to <6> above and a sphingolipid.
<8> 乳酸菌および/またはビフィズス菌の発酵物および/または培養物と、追加のスフィンゴ脂質とを含んでなる、経口摂取用または経腸投与用組成物。 <8> A composition for oral ingestion or enteral administration, comprising a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria and an additional sphingolipid.
<9> 前記<7>または<8>の経口摂取用または経腸投与用組成物において、乳酸菌および/またはビフィズス菌の発酵物および/または培養物と、スフィンゴ脂質との配合比が、スフィンゴ脂質の1mgに対して、乳酸菌および/またはビフィズス菌の発酵物および/または培養物(乾重量(粉末))を1~10000mgで含んでなるのがよい。 <9> The composition for oral ingestion or enteral administration according to <7> or <8> above, wherein the blending ratio of the lactic acid bacteria and / or bifidobacteria fermented product and / or culture product to the sphingolipid is a sphingolipid. 1 mg of lactic acid bacteria and / or bifidobacteria fermented and / or cultured (dry weight (powder)) may be included at 1 to 10,000 mg.
<10> 前記<7>または<8>の経口摂取用または経腸投与用組成物において、乳酸菌および/またはビフィズス菌の発酵物および/または培養物と、スフィンゴ脂質との配合比が、スフィンゴ脂質の1mgに対して、乳酸菌および/またはビフィズス菌の発酵物および/または培養物(湿重量)を0.01~100gで含んでなるのがよい。 <10> In the composition for oral ingestion or enteral administration described in <7> or <8> above, the blending ratio of the lactic acid bacteria and / or bifidobacteria fermented product and / or culture product to the sphingolipid is determined as a sphingolipid. 1 mg of lactic acid bacteria and / or bifidobacteria fermented and / or cultured (wet weight) may be included in an amount of 0.01 to 100 g.
<11> 前記<7>~<10>のいずれかの経口摂取用または経腸投与用組成物において、スフィンゴ脂質はスフィンゴミエリンであるのがよい。 <11> In the composition for oral ingestion or enteral administration according to any one of <7> to <10>, the sphingolipid may be sphingomyelin.
<12> 前記<7>~<11>のいずれかの経口摂取用または経腸投与用組成物は、スフィンゴミエリンの生体内への吸収によって誘発される生体内の作用のために用いられるのがよい。 <12> The composition for oral intake or enteral administration according to any one of the above <7> to <11> is used for an in vivo action induced by absorption of sphingomyelin into the living body. Good.
<13> 前記<12>の経口摂取用または経腸投与用組成物において、前記<7>の生体内の作用が、皮膚の状態の悪化の予防もしくは改善、ガン抑制作用、美肌作用、乳幼児脳発達促進作用、ミトコンドリア機能向上作用、運動機能向上作用、内臓脂肪蓄積抑制および血中アディポネクチン濃度上昇促進作用、および、感染症予防作用からなる群より選択されるものであるのがよい。 <13> In the composition for ingestion or enteral administration according to <12> above, the in vivo action of <7> is prevention or improvement of skin condition deterioration, cancer suppression action, skin beautification, infant brain It is preferable to be selected from the group consisting of a development promoting action, a mitochondrial function improving action, a motor function improving action, a visceral fat accumulation suppressing action and a blood adiponectin concentration raising promoting action, and an infectious disease preventing action.
<14> 前記<7>~<11>のいずれかの経口摂取用または経腸投与用組成物は、皮膚の状態の悪化の予防、抑制または改善用であるのがよい。 <14> The composition for oral intake or enteral administration according to any one of the above <7> to <11> may be used for prevention, suppression or improvement of skin condition deterioration.
<15> 前記<14>の組成物において、皮膚の状態の悪化が、皮膚のバリア機能の悪化であるのがよい。 <15> In the composition according to <14>, the deterioration of the skin state may be a deterioration of the skin barrier function.
<16> 前記<1>~<6>のいずれかのスフィンゴ脂質吸収促進剤、または前記<7>~<15>のいずれかの組成物を含む、飲食品。 <16> A food or drink comprising the sphingolipid absorption promoter of any one of <1> to <6> or the composition of any one of <7> to <15>.
<17> 前記<16>の飲食品において、機能性食品、健康栄養食品、サプリメント、特定保健用食品、機能性表示食品、または疾病リスク低減表示付き食品であるのがよい。 <17> The food and drink according to <16> may be a functional food, a health nutrition food, a supplement, a food for specified health use, a functional display food, or a food with a disease risk reduction display.
<18> 乳酸菌および/またはビフィズス菌の発酵物および/または培養物をスフィンゴ脂質と同時に、スフィンゴ脂質の摂取が望まれる対象に、経口摂取させるか、または経腸投与することを含む、スフィンゴ脂質の吸収促進方法。 <18> Fermented and / or cultured lactic acid bacteria and / or bifidobacteria simultaneously with sphingolipids, or ingested or enterally administered to a subject in whom sphingolipids are desired. Absorption promotion method.
<19>前記<18>の吸収促進方法において、スフィンゴ脂質はスフィンゴミエリンであるのがよい。 <19> In the absorption promotion method according to <18>, the sphingolipid may be sphingomyelin.
本発明のスフィンゴ脂質吸収促進剤によれば、スフィンゴミエリンを摂取した場合に、スフィンゴミエリンの吸収を向上や促進することができ、さらに、安全かつ簡便で、経済的(もしくは効率的)にスフィンゴミエリンを吸収することができる。本発明の吸収促進剤および組成物において使用するヨーグルトは、従来食品として使用の経験があるものであることから、安全性が高く、実際の摂取にあたって簡易であり、経済的にも有利なものである。 According to the sphingolipid absorption enhancer of the present invention, when sphingomyelin is ingested, the absorption of sphingomyelin can be improved or promoted, and further, safe, simple and economical (or efficient) sphingomyelin. Can be absorbed. The yogurt used in the absorption enhancer and composition of the present invention has experience in use as a conventional food, so it is highly safe, simple in actual consumption, and economically advantageous. is there.
以下、本発明の実施形態について説明する。 Hereinafter, embodiments of the present invention will be described.
スフィンゴ脂質吸収促進剤
本発明のスフィンゴ脂質吸収促進剤は、前記したように、乳酸菌および/またはビフィズス菌の発酵物および/または培養物を有効成分とする。ここで、「有効成分とする」とは、本発明による吸収促進剤が、スフィンゴ脂質の吸収を促進する作用を生体内で奏するのに充分な使用量(すなわち、有効量)の乳酸菌および/またはビフィズス菌の発酵物および/または培養物を含有することをいう。
Sphingolipid absorption enhancer As described above, the sphingolipid absorption enhancer of the present invention contains a fermentation product and / or culture product of lactic acid bacteria and / or bifidobacteria as an active ingredient. Here, the term “active ingredient” means that the absorption promoter according to the present invention is used in a sufficient amount (ie, effective amount) of lactic acid bacteria and / or sufficient to exert the action of promoting the absorption of sphingolipids in vivo. It means containing a fermented product and / or culture product of bifidobacteria.
また、ここで、スフィンゴ脂質の「吸収促進」とは、スフィンゴ脂質の生体内への吸収を促進することを意味する。そして、ここでいう「吸収」とは、典型的には、本発明の吸収促進剤と同時または逐次的に経口摂取や経腸投与されたスフィンゴ脂質、または既に体内へ摂取済のスフィンゴ脂質を、消化管や吸収管などにおける生体膜を介して、生体内の循環器(血管系やリンパ系)など中に取り込むことをいい、これにより、実際に吸収されたスフィンゴ脂質は、スフィンゴ脂質もしくはその誘導物質として、生体内への様々な作用を及ぼすことが可能となる。 In addition, here, “absorption promotion” of sphingolipid means promoting absorption of the sphingolipid into the living body. The term “absorption” as used herein typically refers to a sphingolipid that has been orally or enterally administered simultaneously or sequentially with the absorption enhancer of the present invention, or a sphingolipid that has already been ingested into the body. It is taken up into the circulatory organs (vascular system and lymphatic system) in the living body through the biological membrane in the digestive tract and the absorption tract, etc., so that the actually absorbed sphingolipid is sphingolipid or its induction. As a substance, it is possible to exert various actions on the living body.
また、ここでいう「促進」とは、吸収促進剤を使用しない場合に比べて、スフィンゴ脂質の吸収が促進されることを意味し、ここには、吸収量が増加すること、吸収する速度が向上すること、低下した吸収能の改善などを包含する。なお、本発明の好ましい態様において「促進」とは、スフィンゴ脂質の生体内への吸収量が増加する意味で使用される。 The term “promotion” as used herein means that the absorption of sphingolipids is promoted compared to the case where no absorption enhancer is used. Here, the amount of absorption increases and the rate of absorption is increased. Includes improving, improving reduced absorption and the like. In the preferred embodiment of the present invention, “promotion” is used in the sense of increasing the amount of sphingolipid absorbed into the living body.
本明細書において、スフィンゴ脂質は、天然由来のものであり、例えば、牛乳、ヤギ乳、羊乳、馬乳などの乳由来のもの、卵黄由来のもの、大豆、米、トウモロコシ、穀物由来のもの、コンニャク由来、ビート由来などが挙げられ、好ましくは、乳由来のものであり、より好ましくは牛乳由来のものである。スフィンゴ脂質には、スフィンゴミエリン、グルコシルセラミド、ガラクトシルセラミドが包含される。スフィンゴ脂質は、好ましくはスフィンゴリン脂質であり、より好ましくは、スフィンゴミエリンである。これらは、天然原料より慣用の方法により調製することもできるが、市販品を使用しても良い。 In the present specification, sphingolipids are naturally derived, such as those derived from milk such as cow's milk, goat milk, sheep milk, and horse milk, those derived from egg yolk, those derived from soybeans, rice, corn, and grains. , Derived from konjac, beet-derived and the like, preferably derived from milk, more preferably derived from milk. Sphingolipids include sphingomyelin, glucosylceramide, and galactosylceramide. The sphingolipid is preferably a sphingophospholipid, more preferably a sphingomyelin. These can be prepared from natural raw materials by a conventional method, but commercially available products may be used.
本発明において、使用可能なスフィンゴミエリンは、スフィンゴ脂質の一つであり、前記したスフィンゴ脂質と同様に、天然由来のものであり、好ましくは、乳由来のものであり、より好ましくは、牛乳由来のものである。スフィンゴミエリンは、天然原料から慣用の方法によって調製することもできるが、市販品を使用しても良い。 In the present invention, the sphingomyelin that can be used is one of sphingolipids and, like the sphingolipids described above, is naturally derived, preferably milk-derived, more preferably milk-derived. belongs to. Sphingomyelin can be prepared from natural raw materials by a conventional method, but a commercially available product may be used.
本発明の好ましい態様によれば、スフィンゴ脂質吸収促進剤において、乳由来のスフィンゴミエリンの生体内への吸収が促進される。 According to a preferred embodiment of the present invention, absorption of milk-derived sphingomyelin into the living body is promoted in the sphingolipid absorption promoter.
本発明において、スフィンゴ脂質(例えば、スフィンゴミエリン)の吸収は、生体内へのスフィンゴ脂質量を測定することで評価することができる。このとき、例えば、スフィンゴミエリンの一定の分子種に着目し、その分子種が生体内に取り込まれた量を測定することで、スフィンゴミエリンの吸収を評価してもよい。あるいは、スフィンゴミエリンの誘導物質、例えば、スフィンゴミエリンの加水分解により生ずるセラミドが生体内に取り込まれた量を測定することで、スフィンゴミエリンの吸収を評価することもできる。 In the present invention, the absorption of sphingolipid (for example, sphingomyelin) can be evaluated by measuring the amount of sphingolipid into the living body. At this time, for example, the absorption of sphingomyelin may be evaluated by paying attention to a certain molecular species of sphingomyelin and measuring the amount of the molecular species taken into the living body. Alternatively, the absorption of sphingomyelin can be evaluated by measuring the amount of a sphingomyelin inducer, for example, ceramide produced by hydrolysis of sphingomyelin, taken into the living body.
一般的に、スフィンゴミエリン、特に、乳由来のスフィンゴミエリンに含まれる分子種としては、例えば、以下のようなものを挙げることができる:
すなわち、炭素鎖数が16~18であるスフィンゴシンまたはジヒドロスフィンゴシンと炭素鎖が14~26である脂肪酸がそれぞれアミド結合したセラミド構造に、ホスホコリンまたはホスホエタノールアミンが結合したスフィンゴミエリン分子種である。
In general, examples of molecular species contained in sphingomyelin, particularly milk-derived sphingomyelin, include the following:
That is, it is a sphingomyelin molecular species in which phosphocholine or phosphoethanolamine is bound to a ceramide structure in which sphingosine or dihydrosphingosine having a carbon chain number of 16 to 18 and a fatty acid having a carbon chain of 14 to 26 are amide-bonded respectively.
スフィンゴミエリンの吸収では、これら分子種のいずれか、または複数を組み合わせたものに着目して、その量またはその誘導物質の量を測定することによって評価することができる。 The absorption of sphingomyelin can be evaluated by focusing on one or a combination of a plurality of these molecular species and measuring the amount or the amount of the inducer.
前記したように、スフィンゴミエリンは、セラミドとホスホコリンで構成される物質であり、スフィンゴミエリナーゼによって、セラミドとホスホコリンとに加水分解される。セラミドはさらに、セラミダーゼによってスフィンゴイド塩基と脂肪酸とに加水分解される。このため、スフィンゴ脂質吸収促進剤によって、スフィンゴミエリンの吸収が促進される他、セラミドの生体内への吸収も促進される。
このため、本発明のスフィンゴ脂質吸収促進剤によれば、セラミドの生体内への吸収も促進される。
As described above, sphingomyelin is a substance composed of ceramide and phosphocholine, and is hydrolyzed into ceramide and phosphocholine by sphingomyelinase. Ceramide is further hydrolyzed to sphingoid base and fatty acid by ceramidase. For this reason, the sphingolipid absorption promoter promotes the absorption of sphingomyelin and also promotes the absorption of ceramide into the living body.
For this reason, according to the sphingolipid absorption enhancer of the present invention, absorption of ceramide into the living body is also promoted.
本発明の別の態様によれば、乳酸菌および/またはビフィズス菌の発酵物および/または培養物を有効成分とする、セラミド、グルコシルセラミド、および/またはガラクトシルサラミドの吸収促進剤も提供される。このような本発明によるセラミド、グルコシルセラミド、および/またはガラクトシルサラミド脂質吸収促進剤によれば、セラミド、グルコシルセラミド、ガラクトシルサラミド、またはそれらの2以上の組み合わせの生体内への吸収も促進される。 According to another aspect of the present invention, there is also provided an absorption promoter for ceramide, glucosylceramide, and / or galactosylsalamide containing a fermentation product and / or culture product of lactic acid bacteria and / or bifidobacteria as an active ingredient. According to such a ceramide, glucosylceramide, and / or galactosylsalamide lipid absorption enhancer according to the present invention, absorption of ceramide, glucosylceramide, galactosylsalamide, or a combination of two or more thereof into a living body is also promoted. The
本発明において、セラミド、グルコシルセラミド、ガラクトシルセラミドに含まれる分子種としては、例えば、以下のようなものを挙げることができる:
すなわち、炭素鎖数が16~18であるスフィンゴシン、ジヒドロスフィンゴシン、スフィンガジエニン、フィトスフィンゴシンまたはヒドロキシスフィンゲニンと炭素鎖が14~26である脂肪酸またはヒドロキシ脂肪酸がそれぞれアミド結合したセラミド分子種。上記のセラミド分子種にグルコースが結合したグルコシルセラミド分子種。上記のセラミド分子種にガラクトースが結合したガラクトシルセラミド分子種である。
In the present invention, examples of the molecular species contained in ceramide, glucosylceramide, and galactosylceramide include the following:
That is, ceramide molecular species in which sphingosine, dihydrosphingosine, sphingadienin, phytosphingosine or hydroxysphingenin having 16 to 18 carbon chains and amide bonds of fatty acids or hydroxy fatty acids having 14 to 26 carbon chains, respectively. Glucosylceramide molecular species in which glucose is bound to the above ceramide molecular species. This is a galactosylceramide molecular species in which galactose is bound to the above ceramide molecular species.
本発明において、「乳酸菌および/またはビフィズス菌の発酵物および/または培養物」とは、乳酸菌とビフィズス菌の発酵物、乳酸菌の発酵物、ビフィズス菌の発酵物、乳酸菌とビフィズス菌の培養物、乳酸菌の培養物、ビフィズス菌の培養物、およびそれらの組合せを含む意味で使用される。 In the present invention, the “fermented product and / or culture of lactic acid bacteria and / or bifidobacteria” means a fermented product of lactic acid bacteria and bifidobacteria, a fermented product of lactic acid bacteria, a fermented product of bifidobacteria, a cultured product of lactic acid bacteria and bifidobacteria, Used to include lactic acid bacteria cultures, bifidobacteria cultures, and combinations thereof.
本発明において、「乳酸菌」とは、ブドウ糖を資化して対糖収率で50%以上の乳酸を生産する微生物の総称で、生理学的性質としてグラム陽性菌の球菌または桿菌で、運動性なし、胞子形成能なし、カタラーゼ陰性などの特徴を有しているものである。乳酸菌は古来から、発酵乳等を介して世界各地で食されており、極めて安全性の高い微生物と言える。乳酸菌は現在までに、Lactococcus属、Lactobacillus属、Leuconostoc属、Pediococcus属、Streptococcus属、Wissella属、Tetragenococcus属、Oenococcus属、Enterococcus属、Vagococcus属、Carnobacterium属の11属に分類されている。本発明において、これらの乳酸菌を用いることができる。これらの中でも、好適な乳酸菌として、Lactobacillus属、すなわち、Lactobacillus delbrueckii subsp. bulgaricus、Streptococcus thermophilus、Lactobacillus lactis、Lactobacillus gasseriなどが挙げられる。とくに、Lactobacillus delbrueckii subsp. bulgaricusおよびStreptococcus thermophilusの混合スターターを用いることが好ましい。 In the present invention, the term “lactic acid bacteria” is a general term for microorganisms that assimilate glucose and produce lactic acid with a yield of sugar of 50% or more. It has characteristics such as lack of spore formation and negative catalase. Lactic acid bacteria have been eaten from around the world through fermented milk since ancient times, and can be said to be extremely safe microorganisms. To date, lactic acid bacteria have been classified into 11 genera of Lactococcus, Lactobacillus, Leuconostoc, Pediococcus, Streptococcus, Wissella, Tetragenococcus, Oenococcus, Enterococcus, Vagococcus, and Carnobacterium. In the present invention, these lactic acid bacteria can be used. Among these, preferable Lactobacillus includes, for example, Lactobacillus genus, that is, Lactobacillus eckdelbrueckii subsp. Bulgaricus, Streptococcus thermophilus, Lactobacillus lactis, Lactobacillus gasseri and the like. In particular, it is preferable to use a mixed starter of Lactobacillus delbrueckii subsp. Bulgaricus and Streptococcus thermophilus.
本発明において、「ビフィズス菌」とは、ブドウ糖を資化して酢酸や乳酸を生成する微生物であり、Bifidobacterium属に属する微生物である。例えば、Bifidobacterium longum、Bifidobacterium infantis、Bifidobacterium adolescentis、Bifidobacterium breveなどが例示できる。 In the present invention, “Bifidobacterium” is a microorganism that assimilates glucose to produce acetic acid and lactic acid, and belongs to the genus Bifidobacterium. Examples include Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium adolescentis, Bifidobacterium breve and the like.
本発明の一つの好ましい態様によれば、乳酸菌は、ブルガリア菌とサーモフィラス菌の組合せを含むものであり、より好ましくは、ブルガリア菌とサーモフィラス菌の組合せである。 According to one preferred embodiment of the present invention, the lactic acid bacteria include a combination of Bulgarian bacteria and thermophilus bacteria, and more preferably a combination of Bulgarian bacteria and thermophilus bacteria.
また本発明において「発酵物」とは、乳酸菌および/またはビフィズス菌による発酵によって得られた培養物自体をいう。本発明において「発酵物」には、乳酸菌および/またはビフィズス菌の発酵物およびその処理物、例えば、前記培養物(乳酸菌および/またはビフィズス菌発酵物)をろ過・遠心分離もしくは膜分離等で除菌して得られた培養濾液や培養上清液、前記培養濾液・培養上清液や乳酸菌および/またはビフィズス菌発酵物等をエバポレーター等により濃縮した濃縮物、ペースト化物、希釈物又は(凍結、加熱、減圧など)乾燥物が含まれる。
さらに、本発明において、処理物の作成の際は、ろ過、遠心分離、膜分離等の除菌処理、沈殿、濃縮、ペースト化、希釈、乾燥などの前述の処理工程の1つ又は複数を組み合わせて用いることができる。
In the present invention, the “fermented product” refers to a culture itself obtained by fermentation with lactic acid bacteria and / or bifidobacteria. In the present invention, “fermented product” refers to a fermented product of lactic acid bacteria and / or bifidobacteria and a processed product thereof, for example, the culture (lactic acid bacteria and / or bifidobacteria fermented product) removed by filtration, centrifugation, membrane separation, or the like. Concentrated, pasted, diluted or (frozen, concentrated or concentrated, etc.) the culture filtrate or culture supernatant obtained by fungi, the culture filtrate / culture supernatant, lactic acid bacteria and / or bifidobacteria fermentation product, etc. Heat, reduced pressure, etc.) include dried products.
Furthermore, in the present invention, when creating a processed product, one or more of the above-described processing steps such as sterilization treatment such as filtration, centrifugation, and membrane separation, precipitation, concentration, pasting, dilution, and drying are combined. Can be used.
また、本発明において「培養物」の培地としては、例えば、酵母エキスを添加した脱脂粉乳培地、MRS培地などが挙げられる。 In the present invention, examples of the culture medium include nonfat dry milk medium and MRS medium supplemented with yeast extract.
本発明の一つの好ましい態様によれば、「乳酸菌および/またはビフィズス菌の発酵物および/または培養物」は、乳酸菌および/またはビフィズス菌の乳発酵物および/または乳培養物である。さらに本発明の一つのより好ましい態様によれば、「乳酸菌および/またはビフィズス菌の発酵物および/または培養物」は、発酵乳(ヨーグルト)である。ここで、前記ヨーグルトは、好ましくはその上清であることができる。本発明の一つのさらに好ましい態様によれば、「乳酸菌および/またはビフィズス菌の発酵物および/または培養物」は、多糖類である。ここで、前記多糖類は、発酵物および/または培養物由来のものであることが好ましい。 According to one preferred embodiment of the present invention, the “fermented product and / or culture of lactic acid bacteria and / or bifidobacteria” is a fermented milk and / or milk culture of lactic acid bacteria and / or bifidobacteria. Furthermore, according to one more preferable aspect of the present invention, the “fermented product and / or culture product of lactic acid bacteria and / or bifidobacteria” is fermented milk (yogurt). Here, the yogurt may be a supernatant thereof. According to one more preferred embodiment of the present invention, the “fermented product and / or culture of lactic acid bacteria and / or bifidobacteria” is a polysaccharide. Here, the polysaccharide is preferably derived from a fermentation product and / or a culture product.
よって、本発明の別の態様によれば、多糖類を有効成分とするスフィンゴ脂質吸収促進剤が提供される。 Therefore, according to another aspect of the present invention, a sphingolipid absorption promoter comprising a polysaccharide as an active ingredient is provided.
本発明において、「乳発酵物および/または乳培養物」、すなわち、「乳の発酵物および/または乳の培養物」は、乳を含む原料を発酵や培養させてなるものをいう。乳の例としては、牛乳等の獣乳や、その加工品(例えば、脱脂乳、全脂粉乳、脱脂粉乳、れん乳、カゼイン、乳清、生クリーム、コンパウンドクリーム、バター、バターミルクパウダー等)や、大豆由来の豆乳等の植物性乳等が挙げられる。 In the present invention, “milk fermented product and / or milk culture”, that is, “milk fermented product and / or milk cultured product” refers to a product obtained by fermenting or culturing a raw material containing milk. Examples of milk include animal milk such as cow milk and processed products thereof (eg, skim milk, whole milk powder, skim milk powder, spinach, casein, whey, fresh cream, compound cream, butter, buttermilk powder, etc.) And vegetable milk such as soybean milk derived from soybean.
発酵乳の原料として、例えば、発酵乳原料ミックスと呼ばれるものが挙げられる。
発酵乳原料ミックスとは、原料乳および他の成分を含む混合物であり、例えば、原料乳、水、他の任意成分(例えば、砂糖、糖類、甘味料、酸味料、ミネラル、ビタミン、香料等)等の発酵乳の製造に常用される原料を加温して溶解し、混合することによって得ることができる。また、発酵乳は、脱脂粉乳やホエイ分解物などの培養液にペクチン、グアーガム、キサンタンガム、カラギーナン、加工でんぶんなどの増粘剤やゲル化剤を使用できる。乳には、殺菌前のものも、殺菌後のものも含まれる。原料乳の具体的な素材(材料)には、水、生乳、殺菌乳、脱脂乳、全脂粉乳、脱脂粉乳、全脂濃縮乳、脱脂濃縮乳、バターミルク、バター、クリームなどが含まれてもよい。また、ホエイタンパク質濃縮物(WPC)、ホエイタンパク質単離物(WPI)、α-ラクトアルブミン(α-La)、β-ラクトグロブリン(β-Lg)などが含まれてもよい。
As a raw material of fermented milk, what is called fermented milk raw material mix is mentioned, for example.
The fermented milk raw material mix is a mixture containing raw milk and other ingredients, such as raw milk, water, and other optional ingredients (for example, sugar, sugar, sweetener, acidulant, mineral, vitamin, flavor, etc.) It can obtain by heating, melt | dissolving, and mixing the raw material normally used for manufacture of fermented milk. Fermented milk can use thickeners and gelling agents such as pectin, guar gum, xanthan gum, carrageenan, and processed starch in culture solutions such as skim milk powder and whey degradation products. Milk includes those before sterilization and those after sterilization. Specific ingredients (materials) of raw milk include water, raw milk, pasteurized milk, skim milk, whole milk powder, skim milk powder, whole fat concentrated milk, skim concentrated milk, butter milk, butter, cream, etc. Also good. Further, whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin (α-La), β-lactoglobulin (β-Lg) and the like may be included.
発酵乳の製造方法は、原材料を混合(調合)する、原料ミックスの調合工程を含む。原料ミックスの調合工程では、発酵乳を製造する際に用いられる通常の条件を適宜採用すればよい。さらに、本発明の発酵乳の製造方法は、従来の方法と同様に、原料ミックスの(加熱)殺菌工程、原料ミックスの冷却工程、スターターの添加工程、発酵工程、発酵乳の冷却工程を含み、この順番で含むことが望ましい。なお、これらの工程では、発酵乳を製造する際に用いられる通常の条件を適宜採用すればよい。 The method for producing fermented milk includes a raw material mix preparation step in which raw materials are mixed (prepared). What is necessary is just to employ | adopt suitably the normal conditions used when manufacturing fermented milk in the preparation process of a raw material mix. Furthermore, the method for producing fermented milk of the present invention includes a raw material mix (heating) sterilization step, a raw material mix cooling step, a starter addition step, a fermentation step, and a fermented milk cooling step, as in the conventional method. It is desirable to include in this order. In addition, what is necessary is just to employ | adopt suitably the normal conditions used when manufacturing fermented milk in these processes.
乳酸菌等を培養するための培地としては通常で用いられる培地を使用できる。すなわち、主炭素源のほか窒素源、無機物その他の栄養素を程良く含有する培地ならば、いずれの培地も使用可能である。炭素源としてはラクトース、グルコース、スクロース、フラクトース、澱粉加水分解物、廃糖蜜などが使用菌の資化性に応じて使用できる。窒素源としてはカゼインの加水分解物、ホエイタンパク質加水分解物、α-ラクトアルブミン、β-ラクトグロブリン、グリコマクロペプチド、大豆タンパク質加水分解物等の有機窒素含有物が使用できる。ほかに増殖促進剤としては、肉エキス、魚肉エキス、酵母エキス等を使用いることができる。 As a medium for culturing lactic acid bacteria and the like, a medium usually used can be used. That is, any medium can be used as long as it contains a nitrogen source, inorganic substances and other nutrients in addition to the main carbon source. As the carbon source, lactose, glucose, sucrose, fructose, starch hydrolyzate, waste molasses and the like can be used according to the assimilation ability of the bacteria used. As the nitrogen source, organic nitrogen-containing substances such as casein hydrolyzate, whey protein hydrolyzate, α-lactalbumin, β-lactoglobulin, glycomacropeptide, and soy protein hydrolyzate can be used. In addition, as the growth promoter, meat extract, fish extract, yeast extract and the like can be used.
乳酸菌等を培養するための条件としては、嫌気状態が好ましいが、通常で用いられる液体静置培養などによる微好気状態でもよい。この嫌気状態の培養には、炭素ガス気層下で培養する方法などの公知の手法を適用することができるが、他の方法でもかまわない。培養温度は一般に30~47℃が好ましく、より好ましくは35~46℃、さらに好ましくは37℃~45℃である。乳酸菌等を培養中の培地のpHとしては、6~7に維持することが好ましいが、菌が生育する温度であれば他のpH条件でもよい。乳酸菌等の培養時間としては、通常で1~48時間が好ましく、より好ましくは8~36時間、さらに好ましくは10~24時間が好ましい。 As conditions for culturing lactic acid bacteria and the like, an anaerobic state is preferable, but a microaerobic state by liquid stationary culture ordinarily used may be used. For this anaerobic culture, a known method such as a method of culturing in a carbon gas gas layer can be applied, but other methods may be used. In general, the culture temperature is preferably 30 to 47 ° C, more preferably 35 to 46 ° C, and still more preferably 37 ° C to 45 ° C. The pH of the medium in which lactic acid bacteria and the like are cultured is preferably maintained at 6 to 7, but other pH conditions may be used as long as the temperature allows the bacteria to grow. The culture time for lactic acid bacteria and the like is usually preferably 1 to 48 hours, more preferably 8 to 36 hours, still more preferably 10 to 24 hours.
本発明における発酵乳(ヨーグルト)の典型例としては、無脂乳固形分が8重量%以上であり、乳酸菌数又は酵母数が1000万/ml以上である。例えば、1011個/ml以下である。 As a typical example of fermented milk (yogurt) in the present invention, the solid content of non-fat milk is 8% by weight or more, and the number of lactic acid bacteria or the number of yeasts is 10 million / ml or more. For example, it is 10 11 pieces / ml or less.
用途
本発明の有効成分である乳酸菌および/またはビフィズス菌の発酵物および/または培養物は、スフィンゴ脂質の吸収促進活性を有し(後述する実施例1および2)、通常、セラミドの吸収促進活性も有する。したがって、本発明のスフィンゴ脂質吸収促進剤を使用することで、生体内でのスフィンゴ脂質の吸収を向上させることができるため、生体内でスフィンゴ脂質またはその誘導物質の存在により奏される種々の作用を、より一層向上させることができる。この点は、スフィンゴ脂質がスフィンゴミエリンである場合も当然同様のことが言え、本発明のスフィンゴミエリン吸収促進剤を使用することで、生体内でのスフィンゴミエリンの吸収を向上させることができるため、生体内でスフィンゴミエリンまたはその誘導物質の存在により奏される種々の作用を、より一層向上させることができる。
Use The fermented product and / or culture of lactic acid bacteria and / or bifidobacteria, which are active ingredients of the present invention, have sphingolipid absorption promoting activity (Examples 1 and 2 to be described later), and usually ceramide absorption promoting activity. Also have. Therefore, the use of the sphingolipid absorption promoter of the present invention can improve the absorption of the sphingolipid in the living body, and thus various effects exhibited by the presence of the sphingolipid or its derivative in the living body. Can be further improved. This point is naturally the same when the sphingolipid is sphingomyelin, and by using the sphingomyelin absorption promoter of the present invention, it is possible to improve the absorption of sphingomyelin in vivo, Various actions exhibited by the presence of sphingomyelin or a derivative thereof in a living body can be further improved.
さらに同様に、スフィンゴ脂質がセラミド、グリコシルセラミド、またはガラクトシルセラミドである場合、本発明のセラミド、グリコシルセラミド、またはガラクトシルセラミドの吸収促進剤を使用することで、生体内でのセラミド、グリコシルセラミド、またはガラクトシルセラミドの吸収を向上させることができる。このため、生体内でセラミド、グリコシルセラミド、またはガラクトシルセラミド、さらにそれらの誘導物質の存在により奏される種々の作用を、より一層向上させることもできる。 Furthermore, similarly, when the sphingolipid is ceramide, glycosyl ceramide, or galactosyl ceramide, by using the ceramide, glycosyl ceramide, or galactosyl ceramide absorption enhancer of the present invention, in vivo ceramide, glycosyl ceramide, or Absorption of galactosylceramide can be improved. For this reason, various actions exhibited by the presence of ceramide, glycosylceramide, or galactosylceramide and their derivatives in vivo can be further improved.
生体内でのスフィンゴミエリンまたはその誘導物質の存在量の増加によって、皮膚の状態の悪化(皮膚のバリア機能の低下、皮膚の乾燥・かさつき、角層の水分量の低下、アトピー性皮膚炎など)の向上、改善、増強、予防効果の向上が奏されうる。 Deterioration of skin condition due to increased presence of sphingomyelin or its inducer in the body (decreased skin barrier function, dry skin and skin, decreased moisture content of stratum corneum, atopic dermatitis, etc. ) Can be improved, improved, enhanced, and improved in preventive effect.
また、生体内でのスフィンゴミエリンまたはその誘導物質の存在量の増加によって、ガン(大腸がん)抑制作用(菅原達也、「食品機能性成分としてのスフィンゴ脂質の消化と吸収」、日本栄養・食糧学会誌、第66巻4号、pp.177-183 (2013))、美肌作用(特開2008-184428号公報)、乳幼児脳発達促進作用(特許第3203485号)、ミトコンドリア機能向上作用(特開2011-157329号公報)、運動機能向上作用(特開2014-141496号公報)、内臓脂肪蓄積抑制および血中アディポネクチン濃度上昇促進作用(抗高血糖作用、抗高脂血症作用)(特開2007-320900号公報)、感染症予防作用(特開2008-037788号公報)などが発揮されうる。 In addition, by increasing the amount of sphingomyelin or its inducer in vivo, cancer (colon cancer) inhibitory action (Tatsuya Sugawara, “Digestion and absorption of sphingolipid as a food functional ingredient”, Japanese nutrition and food Academic Journal, Vol. 66, No. 4, pp. 177-183 (2013)), skin beautification (JP 2008-184428), infant brain development promotion (Patent No. 3203485), mitochondrial function improvement (JP 2011-157329), motor function improving action (Japanese Patent Laid-Open No. 2014-14196), visceral fat accumulation suppression and blood adiponectin concentration increase promoting action (anti-hyperglycemic action, anti-hyperlipidemic action) (JP 2007) -320900), infectious disease prevention action (Japanese Patent Laid-Open No. 2008-037788), and the like.
よって、本発明のスフィンゴ脂質吸収促進剤により、スフィンゴ脂質の吸収が促進されることで、これらの効果が得られる。 Therefore, these effects can be obtained by promoting the absorption of sphingolipids by the sphingolipid absorption promoter of the present invention.
さらに、後述する実施例3で示したように、スフィンゴ脂質の吸収促進により、紫外線による皮膚バリア機能の低下状態において、皮膚バリア機能をより一層改善することができる。 Furthermore, as shown in Example 3 to be described later, by promoting the absorption of sphingolipid, the skin barrier function can be further improved in the state where the skin barrier function is lowered by ultraviolet rays.
本発明において、皮膚の状態の悪化とは、例えば、皮膚のバリア機能の低下、皮膚の乾燥、皮膚のかさつき、角層の水分量の低下、アトピー性皮膚炎などが包含される。皮膚のバリア機能の低下には、バリア機能の維持も包含される。また、皮膚のバリア機能の低下は、好ましくは、紫外線の照射下における皮膚のバリア機能の低下である。 In the present invention, the deterioration of the skin condition includes, for example, a reduction in skin barrier function, skin drying, skin roughness, a decrease in the amount of water in the stratum corneum, and atopic dermatitis. Reduction of the barrier function of the skin includes maintenance of the barrier function. Further, the reduction in the skin barrier function is preferably a reduction in the skin barrier function under the irradiation of ultraviolet rays.
また、ここで、悪化した状態の「予防、抑制または改善」は、そのような状態の、調節、進行の遅延、緩和、発症予防、再発予防などを包含する意味で使用される。 Also, here, “prevention, suppression or improvement” of an exacerbated state is used in a sense encompassing adjustment, delay of progression, mitigation, prevention of onset, prevention of recurrence, etc. of such a state.
よって、本発明によれば、スフィンゴ脂質の吸収促進により、生体内吸収されるスフィンゴ脂質を増やすことができるため、その結果、スフィンゴ脂質の生体内への吸収によって誘発される生体内の作用(機能、効能)の向上、改善、増強を図ることができる。なお、ここでいう生体内の作用とは、スフィンゴ脂質の生体内への吸収によって誘発されるものであって、具体的には、前記したように、種々の効果のものが上げられる。したがって、本発明によれば、スフィンゴ脂質吸収により誘発される生体内の作用(機能)の増強剤(スフィンゴ脂質吸収(摂取)に伴う機能の強化剤)を提供することもできる。 Therefore, according to the present invention, it is possible to increase the amount of sphingolipid absorbed in the living body by promoting the absorption of the sphingolipid, and as a result, the in vivo action (function) induced by the absorption of the sphingolipid into the living body. , Efficacy) can be improved, improved and enhanced. The in vivo action referred to here is induced by absorption of sphingolipid into the living body, and specifically has various effects as described above. Therefore, according to the present invention, it is also possible to provide an enhancer of an action (function) in vivo induced by absorption of sphingolipid (an enhancer of function accompanying absorption (ingestion) of sphingolipid).
経口摂取用または経腸投与用組成物
前記したように、本発明によれば、本発明の有効成分、すなわち乳酸菌および/またはビフィズス菌の発酵物および/または培養物と、スフィンゴ脂質とを含んでなる、経口摂取用または経腸投与用組成物が提供される。この組成物は、そのような有効成分として、本発明のスフィンゴ脂質吸収促進剤を含んでなるということもできる。
Composition for Oral Intake or Enteral Administration As described above, according to the present invention, the active ingredient of the present invention, that is, a fermented and / or cultured product of lactic acid bacteria and / or bifidobacteria, and a sphingolipid. A composition for oral ingestion or enteral administration is provided. It can also be said that this composition comprises the sphingolipid absorption promoter of the present invention as such an active ingredient.
乳酸菌および/またはビフィズス菌の発酵物および/または培養物では、多くの場合に、それ自体にスフィンゴ脂質が既に含まれているが、本発明の好ましい態様において、本発明の組成物は、乳酸菌および/またはビフィズス菌の発酵物および/または培養物と、追加のスフィンゴ脂質とを含んでなる。このため、本発明の組成物は、従来のヨーグルトなどのような、乳酸菌および/またはビフィズス菌の発酵物および/または培養物とは区別されうるものである。
ここで、「追加のスフィンゴ脂質」とは、乳酸菌および/またはビフィズス菌の発酵物および/または培養物にスフィンゴ脂質が含まれている場合に、乳酸菌および/またはビフィズス菌の発酵物および/または培養物に含まれているスフィンゴ脂質自体の量を超えて、追加的に組成物中に存在するスフィンゴ脂質のことを意味する。
Lactic acid bacteria and / or bifidobacteria fermentations and / or cultures often already contain sphingolipids themselves, but in a preferred embodiment of the invention the composition of the invention comprises lactic acid bacteria and And / or bifidobacteria fermentation and / or culture and additional sphingolipids. For this reason, the composition of the present invention can be distinguished from a fermentation product and / or culture product of lactic acid bacteria and / or bifidobacteria such as conventional yogurt.
Here, “additional sphingolipid” refers to a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria when a sphingolipid is contained in the fermented product and / or culture of lactic acid bacteria and / or bifidobacteria. It means a sphingolipid that is additionally present in the composition beyond the amount of the sphingolipid itself contained in the product.
追加のスフィンゴ脂質は、スフィンゴ脂質自体をそのまま使用してもよいが、例えば、乳由来のスフィンゴミエリンの高含有のリン脂質濃厚物(MPL)が挙げられる。クリーム又はバターから、あるいはバターオイルを製造する際の副産物であるバターゼラムから、アセトン(溶媒)および/またはエタノールの不溶画分として得ることもできる。バターゼラムは、市乳分野でも利用されており、入手可能である(例えば、ニュージーランド、Tatua社製)。バターゼラムには、スフィンゴミエリンが局在するMFGMが多く含まれており、原料として好適である。 As the additional sphingolipid, the sphingolipid itself may be used as it is, and examples thereof include a high content phospholipid concentrate (MPL) of milk-derived sphingomyelin. It can also be obtained as an insoluble fraction of acetone (solvent) and / or ethanol from cream or butter or from butter ram which is a by-product in producing butter oil. Bataselam is also used in the city milk field and is available (for example, manufactured by Tatua, New Zealand). Bataselam is rich in MFGM in which sphingomyelin is localized, and is suitable as a raw material.
バターゼラムからスフィンゴミエリンが局在するリン脂質の分画を分離するには、リン脂質がアセトンおよび/またはエタノールに不溶性であるという性質を利用する。複数回のアセトンの抽出により、中性脂質を含むアセトン可溶性画分を除去し、リン脂質が濃縮されたアセトン不溶性画分を得る。このアセトン不溶性画分を減圧濃縮してアセトンを除去し、この濃縮物を殺菌後に凍結乾燥してから、この乾燥物を粉砕して、乳由来のリン脂質画分を得るなどの形態で組成物に対して使用してもよい。 In order to separate the fraction of phospholipids where sphingomyelin is localized from Bataselam, the property that phospholipids are insoluble in acetone and / or ethanol is used. Acetone-soluble fraction containing neutral lipid is removed by multiple extractions of acetone to obtain an acetone-insoluble fraction enriched in phospholipid. The acetone-insoluble fraction is concentrated under reduced pressure to remove acetone, and the concentrate is freeze-dried after sterilization, and then the dried product is crushed to obtain a milk-derived phospholipid fraction. May be used against.
また、鶏皮粉末から総脂質を抽出し、乾燥処理した乾燥総脂質を、脂肪族炭化水素系溶剤と水溶性ケトン系溶剤との混合溶剤で抽出処理し、スフィンゴミエリンを主体とする不溶部を、水と水溶性ケトン系溶剤との混合溶剤で抽出処理し、可溶部に含まれる非脂質成分を除去したスフィンゴミエリンの抽出方法が挙げられる。魚介類、獣鳥類からの抽出方法などの既存の方法を用いることができる。風味の観点からは、乳由来のスフィンゴミエリンが好ましい。 In addition, the total lipid was extracted from chicken skin powder, and the dried total lipid was dried and extracted with a mixed solvent of an aliphatic hydrocarbon solvent and a water-soluble ketone solvent, and an insoluble portion mainly composed of sphingomyelin was removed. And a method for extracting sphingomyelin by extraction with a mixed solvent of water and a water-soluble ketone solvent and removing non-lipid components contained in the soluble part. Existing methods such as extraction methods from seafood and animal birds can be used. From the viewpoint of flavor, milk-derived sphingomyelin is preferred.
本発明の組成物において、乳酸菌および/またはビフィズス菌の発酵物および/または培養物は、セットタイプヨーグルト(固形状発酵乳)、ソフトタイプヨーグルト(糊状発酵乳)、ドリンクヨーグルト(液状発酵乳)などの各種形態のヨーグルトであってもよく、また、穀物や果物、野菜、栄養成分などを含むヨーグルトであってもよい。 In the composition of the present invention, fermented products and / or cultures of lactic acid bacteria and / or bifidobacteria are set type yogurt (solid fermented milk), soft type yogurt (pasted fermented milk), drink yogurt (liquid fermented milk). Various forms of yogurt such as cereals, fruits, vegetables, and nutrient ingredients may also be used.
本発明の経口摂取用または経腸投与用組成物は、好ましくは、スフィンゴ脂質の生体内への吸収性が高められたものであり、より好ましくはスフィンゴミエリンの生体内への吸収性が高められたものである。すなわち、本発明の経口摂取用または経腸投与用組成物は、「スフィンゴ脂質高吸収性」、好ましくは「スフィンゴミエリン高吸収性」の経口摂取用または経腸投与用組成物ということができる。なお、「スフィンゴ脂質高吸収性」または「スフィンゴミエリン高吸収性」であることは、例えば、後述する実施例1または2のように、既存のヨーグルトなどの場合におけるスフィンゴミエリン吸収量と比較することで確認することができる。 The composition for oral ingestion or enteral administration of the present invention is preferably one in which the absorption of sphingolipids into the living body is enhanced, more preferably the absorption of sphingomyelin into the living body is enhanced. It is a thing. That is, the composition for oral ingestion or enteral administration of the present invention can be referred to as a “sphingolipid superabsorbent”, preferably a “sphingomyelin superabsorbent” composition for oral ingestion or enteral administration. Note that “high sphingolipid absorbency” or “high sphingomyelin high absorbency” is to be compared with the amount of sphingomyelin absorbed in the case of an existing yogurt or the like as in Example 1 or 2 described later, for example. Can be confirmed.
スフィンゴ脂質の高吸収性またはスフィンゴミエリンの高吸収性の観点からは、本発明の経口摂取用または経腸投与用組成物において、乳酸菌および/またはビフィズス菌の発酵物および/または培養物と、スフィンゴ脂質との配合比が、スフィンゴ脂質の1mgに対して、乳酸菌および/またはビフィズス菌の発酵物および/または培養物(乾重量(粉末))を好ましくは1~10000mg、より好ましくは5~5000mg、さらに好ましくは10~750mgで含んでなることとなる。 From the viewpoint of superabsorbency of sphingolipid or superabsorbency of sphingomyelin, in the composition for oral intake or enteral administration of the present invention, a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria, and sphingo The blending ratio with lipid is preferably 1 to 10000 mg, more preferably 5 to 5000 mg of lactic acid bacteria and / or bifidobacteria fermentation and / or culture (dry weight (powder)) per 1 mg of sphingolipid. More preferably, it is contained in an amount of 10 to 750 mg.
同様に、スフィンゴ脂質の高吸収性またはスフィンゴミエリンの高吸収性の観点からは、本発明の経口摂取用または経腸投与用組成物において、乳酸菌および/またはビフィズス菌の発酵物および/または培養物と、スフィンゴ脂質の配合比が、スフィンゴ脂質の1mgに対して、乳酸菌および/またはビフィズス菌の発酵物および/または培養物(湿重量)を好ましくは0.01~100g、より好ましくは0.05~50g、さらに好ましくは0.1~7.5gで含んでなることとなる。 Similarly, from the viewpoint of the high absorbability of sphingolipid or the high absorbability of sphingomyelin, the fermented product and / or culture of lactic acid bacteria and / or bifidobacteria in the composition for oral consumption or enteral administration of the present invention And the ratio of sphingolipid to 1 mg of sphingolipid, preferably 0.01 to 100 g, more preferably 0.05 to lactic acid bacteria and / or bifidobacteria fermented product and / or culture (wet weight). To 50 g, more preferably 0.1 to 7.5 g.
本発明の経口摂取用または経腸投与用組成物は、好ましくは、スフィンゴミエリンの生体内への吸収によって誘発される生体内の作用のために用いられる。そして、本発明の経口摂取用または経腸投与用組成物は、より好ましくは,前記の生体内の作用が、皮膚の状態の悪化の予防もしくは改善、ガン抑制作用、美肌作用、乳幼児脳発達促進作用、ミトコンドリア機能向上作用、運動機能向上作用、内臓脂肪蓄積抑制および血中アディポネクチン濃度上昇促進作用、および、感染症予防作用からなる群より選択される作用のために用いられる。 The composition for oral ingestion or enteral administration of the present invention is preferably used for in vivo action induced by absorption of sphingomyelin into the living body. The composition for oral ingestion or enteral administration according to the present invention is more preferably such that the action in the living body is prevention or improvement of skin condition deterioration, cancer suppression action, skin beautification, infant brain development promotion. It is used for an action selected from the group consisting of an action, an action to improve mitochondrial function, an action to improve motor function, an action to suppress visceral fat accumulation and an increase in blood adiponectin concentration, and an action to prevent infection.
本発明の経口摂取用または経腸投与用組成物は、好ましくは、皮膚の状態の悪化の予防、抑制または改善作用のために用いられる。ここで、皮膚の状態の悪化は、皮膚のバリア機能の悪化であることが好ましい。そして、皮膚のバリア機能の悪化は、紫外線の照射によるものであることが好ましい。 The composition for oral intake or enteral administration of the present invention is preferably used for preventing, suppressing or improving the deterioration of the skin condition. Here, the deterioration of the skin condition is preferably a deterioration of the barrier function of the skin. And it is preferable that the deterioration of the barrier function of the skin is due to the irradiation of ultraviolet rays.
本発明の組成物は、一つの好ましい態様として、医薬組成物であることができる。
本発明において、医薬組成物とは、製剤化のために許容されうる添加剤を併用して、常法に従い、経口製剤または非経口製剤として調製したものである。簡易性の点からは、経口製剤であることが好ましい。経口製剤の場合には、錠剤、散剤、細粒剤、顆粒剤、カプセル剤、丸剤、徐放剤などの固形製剤、溶液、懸濁液、乳濁液などの液状製剤の形態をとることができる。製剤化のために許容されうる添加剤としては、例えば、賦形剤、安定剤、防腐剤、湿潤剤、乳化剤、滑沢剤、甘味料、着色料、香料、緩衝剤、酸化防止剤、pH調整剤などが挙げられる。
The composition of this invention can be a pharmaceutical composition as one preferable aspect.
In the present invention, the pharmaceutical composition is prepared as an oral preparation or a parenteral preparation according to a conventional method using additives that are acceptable for formulation. From the viewpoint of simplicity, an oral preparation is preferable. For oral preparations, take the form of solid preparations such as tablets, powders, fine granules, granules, capsules, pills, sustained-release preparations, and liquid preparations such as solutions, suspensions, and emulsions. Can do. Additives that are acceptable for formulation include, for example, excipients, stabilizers, preservatives, wetting agents, emulsifiers, lubricants, sweeteners, colorants, fragrances, buffers, antioxidants, pH Examples thereof include regulators.
また、本発明によれば、本発明のスフィンゴ脂質吸収促進剤、または前記した経口摂取用または経腸投与用組成物を含んでなる、飲食品が提供される。 Also, according to the present invention, there is provided a food or drink comprising the sphingolipid absorption promoter of the present invention or the composition for oral intake or enteral administration described above.
このような本発明の組成物および飲食品は、例えば、本発明の吸収促進剤またはその有効成分を、その組成物および飲食品の材料成分に添加することを含んでなる製造方法によって製造することができる。 Such a composition and food / beverage products of this invention are manufactured by the manufacturing method which comprises adding the absorption promoter of this invention, or its active ingredient to the composition and the material component of food / beverage products, for example. Can do.
本発明の飲食品には、必要に応じて、任意の成分を加えることができる。このような任意の添加可能な成分としては、特段の制限はないが、通常、飲食品に配合される成分、甘味料、酸味料、野菜や果物や種実の汁やそのエキス、ビタミン、ミネラル、アミノ酸などの栄養素、乳酸菌、ビフィズス菌、プロピオン酸菌などの有用な微生物やその培養物、オリゴ糖などの機能性をもつ糖類、ローヤルゼリー、コラーゲン、セラミド、グルコサミン、アスタキサンチン、ポリフェノールなどの既存の機能性素材、香料、pH調整剤、賦形剤、酸味料、着色料、乳化剤、保存料などを配合することができる。 Arbitrary ingredients can be added to the food and drink of the present invention as required. As such optional components that can be added, there are no particular restrictions, but usually ingredients to be blended in foods and drinks, sweeteners, acidulants, vegetable and fruit juices and their extracts, vitamins, minerals, Nutrients such as amino acids, useful microorganisms such as lactic acid bacteria, bifidobacteria and propionic acid bacteria and their cultures, functional sugars such as oligosaccharides, royal jelly, collagen, ceramide, glucosamine, astaxanthin and polyphenols A raw material, a fragrance | flavor, a pH adjuster, an excipient | filler, a sour agent, a coloring agent, an emulsifier, a preservative, etc. can be mix | blended.
本発明において、飲食品とは、医薬組成物以外のものであって、溶液、懸濁液、乳濁液、粉末、固体成形物など、経口摂取可能な形態であればよく特に限定されない。具体的には、例えば、乳飲料、ヨーグルト類、乳酸菌飲料、発酵乳、アイスクリーム類、クリーム類、チーズ類などの乳製品;清涼飲料、果汁飲料、野菜飲料、豆乳飲料、コーヒー飲料、茶飲料、ゼリー飲料、ココア、スムージーなどの粉末飲料やスポーツ粉末飲料、栄養強化の粉末飲料、美容用の粉末食品、粉末スープ、蒸しパンのもと、濃縮飲料、アルコール飲料などの飲料類;パン、パスタ、麺、ケーキミックス、唐揚げ粉、パン粉などの小麦粉製品;チョコレート、ガム、飴、クッキー、グミ、スナック、和菓子、ゼリー、プリンなどのデザート菓子などの菓子類;加工調味料、風味調味料、調理ミックスなどの調味料;カレー、バスタソース、ポトフ、シチュー、和風食品のレトルト食品;加工油脂、バター、マーガリン、スプレッド、マヨネーズなどの油脂類;フリーズドライ食品などの即席食品類;農産缶詰、ジャム・マーマレード類、漬け物、煮豆、シリアル、雑炊などの農産加工品;水産加工品;畜産加工品;ピッツア、ドリア、グラタン、惣菜、フライなど冷凍食品;流動食、さらには動物の飼料、タブレット、口腔内に使用する化粧品などが挙げられる。 In the present invention, the food and drink are other than the pharmaceutical composition and are not particularly limited as long as they are ingestible forms such as solutions, suspensions, emulsions, powders, and solid molded products. Specifically, for example, dairy products such as milk drinks, yogurts, lactic acid bacteria drinks, fermented milk, ice creams, creams, cheeses; soft drinks, fruit juice drinks, vegetable drinks, soy milk drinks, coffee drinks, tea drinks Jelly drinks, cocoa, smoothie powdered drinks and sports powdered drinks, nutrition-enriched powdered drinks, cosmetic powdered foods, powdered soup, steamed bread, concentrated drinks, alcoholic drinks, etc .; bread, pasta , Flour products such as noodles, cake mix, fried flour, bread crumbs; confectionery such as chocolate, gum, candy, cookies, gummi, snacks, Japanese confectionery, jelly, pudding, etc .; processed seasonings, flavor seasonings, Seasoning such as cooking mix; curry, busta sauce, potof, stew, Japanese food retort food; processed oil, butter, margarine, spray Oils and fats such as dough and mayonnaise; Instant foods such as freeze-dried foods; Agricultural processed products such as canned agricultural products, jams and marmalades, pickles, boiled beans, cereals, miscellaneous foods; processed marine products; processed livestock products; Frozen foods such as gratin, sugar beet, and fries; liquid foods, animal feeds, tablets, and cosmetics used in the oral cavity.
本発明の一つの好ましい態様によれば、飲食品は、乳飲料(加工乳を含んでもよい)、発酵乳、清涼飲料、ゼリー飲料、タブレット、美容用の粉末食品、粉末飲料、流動食、液状の調製粉乳であり、より好ましい態様によれば、飲食品は、乳飲料、発酵乳、清涼飲料、ゼリー飲料、調製粉乳のタブレット、美容用の粉末食品であり、さらに好ましい態様によれば、飲食品は、乳飲料(加工乳を含んでもよい)、発酵乳である。 According to one preferred embodiment of the present invention, the food and drink are milk drinks (which may include processed milk), fermented milk, soft drinks, jelly drinks, tablets, cosmetic powdered foods, powdered drinks, liquid foods, liquids. According to a more preferred embodiment, the food and drink is a milk beverage, fermented milk, soft drink, jelly beverage, prepared milk powder tablet, cosmetic powdered food, and according to a more preferred embodiment, the food and drink The product is a milk beverage (which may include processed milk), fermented milk.
また、飲食品には、機能性食品、健康栄養食品、サプリメント、健康食品、特定保健用食品、機能性表示食品、栄養機能食品、病者用食品、乳幼児用調製粉乳、妊産婦もしくは授乳婦用粉乳、または疾病リスク低減表示を付した飲食品のような分類のものも包含される。本発明の一つの好ましい態様によれば、飲食品は、機能性食品、健康栄養食品、サプリメント、特定保健用食品、機能性表示食品、または疾病リスク低減表示付き食品である。 In addition, functional foods, health nutrition foods, supplements, health foods, foods for specified health use, functional indication foods, nutritional functional foods, foods for the sick, infant formulas, milk powders for pregnant and lactating women Or foods and beverages with a disease risk reduction label are included. According to one preferred embodiment of the present invention, the food or drink is a functional food, a health nutrition food, a supplement, a food for specified health use, a functional display food, or a food with a disease risk reduction display.
なお、ここで、疾病リスク低減の表示とは、疾病リスクを低減する可能性のある飲食品の表示であって、FAO/WHO合同食品規格委員会(コーデックス委員会)の定める規格に基づいて、またはその規格を参考にして、定められた表示または認められた表示であることができる。 Here, the indication of disease risk reduction is the indication of food and drink that may reduce the disease risk, and is based on the standards established by the FAO / WHO Joint Food Standards Committee (Codex Committee). , Or with reference to the standard, it can be a defined or recognized display.
よって、本発明の飲食品は、例えば、皮膚状態の悪化の改善または緩和を期待する消費者に適した食品、皮膚の状態悪化の改善に適した食品、すなわち、所謂、特定保健用食品もしくは機能性表示食品、として提供することができる。 Therefore, the food and drink of the present invention are, for example, foods suitable for consumers who expect improvement or alleviation of skin condition deterioration, foods suitable for improvement of skin condition deterioration, that is, so-called foods for specific health use or functions It can be provided as a sex indication food.
本発明の飲食品および組成物において、スフィンゴミエリンの吸収に伴う所望の効果を得るためには、飲食品および組成物におけるスフィンゴミエリンの含有量を、所定の範囲に設定することが望ましい。具体的な含有量は、飲食品もしくは組成物の種類、形態や、予防・改善の目的などによって変化させることができるため、一律に規定することは難しいが、本発明の組成物では、成人(体重:60kg)が1日当たり、乳由来のスフィンゴミエリンを、0.5~1500mg、好ましくは1~1000mg、より好ましくは5~500mgで摂取可能な有効量に調整されたものであることができる。 In the food and drink and composition of the present invention, in order to obtain a desired effect associated with the absorption of sphingomyelin, it is desirable to set the content of sphingomyelin in the food and drink and the composition within a predetermined range. The specific content can be changed depending on the type and form of the food or drink or the composition, the purpose of prevention / improvement, etc., and thus it is difficult to define it uniformly, but in the composition of the present invention, the adult ( (Weight: 60 kg) per day, milk-derived sphingomyelin can be adjusted to an effective amount that can be ingested at 0.5 to 1500 mg, preferably 1 to 1000 mg, more preferably 5 to 500 mg.
スフィンゴ脂質、例えば、スフィンゴミエリンの含量では、慣用の方法によって測定することができるが、例えば、後述する実施例1および2の記載に従って測定してもよい。また、例えば、液体クロマトグラフィーを用い、カラムとして、AQUASIL SP100(4.6X250mm、センシュー科学社)を用いて測定することができる。 The content of sphingolipid, for example, sphingomyelin, can be measured by a conventional method, but may be measured, for example, according to the description in Examples 1 and 2 described later. Moreover, for example, it can measure using liquid chromatography and using AQUASIL SP100 (4.6X250mm, Senshu Scientific Co., Ltd.) as a column.
このとき、移動相として、例えば、0.5mM リン酸-クエン酸緩衝液(pH:3.0)とメタノールを5対95の割合で混合させた溶液を用いるとよい。測定時間を20分間に設定し、移動相の流速を0.6mL/分、カラム温度を40℃に設定し、吸光度を205nmとして検出することができる。標準物質として、例えば、スフィンゴミエリン(乳由来、長良サイエンス社)を用いることができ、面積比により定量することができる。 At this time, as the mobile phase, for example, a solution in which 0.5 mM phosphate-citrate buffer (pH: 3.0) and methanol are mixed at a ratio of 5 to 95 may be used. The measurement time can be set to 20 minutes, the flow rate of the mobile phase can be set to 0.6 mL / min, the column temperature can be set to 40 ° C., and the absorbance can be detected at 205 nm. As a standard substance, for example, sphingomyelin (derived from milk, Nagara Science Co., Ltd.) can be used, and it can be quantified by the area ratio.
本発明の別の態様によれば、飲食品および組成物における有効成分の含量は、一包装形態当たりで規定することもでき、例えば、飲食品の場合、スフィンゴ脂質の含量は5~1500mg、好ましくは6~1000mg、より好ましくは7~500mgで含むものであり、また、組成物の場合、スフィンゴ脂質の含量は0.5~1500mg、好ましくは1~1000mg、より好ましくは5~500mgで含むものであることができる。また、一包装形態当たりの量(含量)は、1回の摂取量に限らず、複数回分または複数日分(例えば、30日分)の摂取量を包括してもよく、例えば、飲食品の場合、スフィンゴ脂質の含量は5~45000mg、好ましくは6~30000mg、より好ましくは7~15000mgで含むものであり、また、組成物の場合、スフィンゴ脂質の含量は0.5~45000mg、好ましくは1~30000mg、より好ましくは5~15000mgで含むものであることができる。 According to another aspect of the present invention, the content of the active ingredient in foods and drinks and compositions can be defined per packaging form. For example, in the case of foods and drinks, the content of sphingolipids is preferably 5 to 1500 mg. 6 to 1000 mg, more preferably 7 to 500 mg, and in the case of a composition, the content of sphingolipid is 0.5 to 1500 mg, preferably 1 to 1000 mg, more preferably 5 to 500 mg. be able to. In addition, the amount (content) per packaging form is not limited to a single intake, and may include intakes for multiple doses or multiple days (for example, for 30 days). In this case, the content of sphingolipid is 5 to 45000 mg, preferably 6 to 30000 mg, more preferably 7 to 15000 mg. In the case of the composition, the content of sphingolipid is 0.5 to 45000 mg, preferably 1 It can be contained in an amount of ˜30000 mg, more preferably 5 to 15000 mg.
従来の一般的な乳飲料、発酵乳では、脂質の1g当たり、リン脂質が20mgで含まれるが、本発明の乳飲料、発酵乳では、脂質の1g当たり、リン脂質が25~3000mgで含まれ、好ましくは30~2500mg、より好ましくは40~2000mg、さらに好ましくは、50~1500mgで含まれるものであることができる。また、従来の一般的な乳飲料、発酵乳では、脂質の1g当たり、スフィンゴミエリンが6mgで含まれるが、本発明の飲食品または組成物では、脂質の1g当たり、スフィンゴミエリンが7~1500mgで含まれ、好ましくは8~1250mg、より好ましくは9~1000mg、さらに好ましくは、10~750mgで含まれるものであることができる。すなわち、本発明の一つの好ましい態様においては、スフィンゴミエリン含量が意図的に高められたものを使用する。 The conventional general milk drink and fermented milk contain 20 mg of phospholipid per gram of lipid, whereas the milk drink and fermented milk of the present invention contain 25 to 3000 mg of phospholipid per gram of lipid. , Preferably 30 to 2500 mg, more preferably 40 to 2000 mg, and still more preferably 50 to 1500 mg. The conventional general milk drink and fermented milk contain 6 mg of sphingomyelin per gram of lipid, but the food or drink or composition of the present invention contains 7 to 1500 mg of sphingomyelin per gram of lipid. Contained, preferably 8 to 1250 mg, more preferably 9 to 1000 mg, and still more preferably 10 to 750 mg. That is, in one preferred embodiment of the present invention, those having an intentionally increased sphingomyelin content are used.
本発明の乳飲料、発酵乳では、脂質を通常量で含む(例えば、脂質を3重量%で含む)場合、リン脂質が1~300mg/gで含まれ、好ましくは1.5~250mg/g、より好ましくは2~200mg/g、さらに好ましくは、2.5~150mg/gで含まれるものであることができる。また、本発明の飲食品または組成物では、脂質を通常量で含む場合、スフィンゴミエリンが0.2~60mg/gで含まれ、好ましくは0.25~50mg/g、より好ましくは0.3~40mg/g、さらに好ましくは、0.35~30mg/gで含まれるものであることができる。 In the milk beverage and fermented milk of the present invention, when lipid is contained in a normal amount (for example, 3% by weight of lipid), phospholipid is contained at 1 to 300 mg / g, preferably 1.5 to 250 mg / g. More preferably 2 to 200 mg / g, still more preferably 2.5 to 150 mg / g. In the food or drink or composition of the present invention, when lipid is contained in a normal amount, sphingomyelin is contained at 0.2 to 60 mg / g, preferably 0.25 to 50 mg / g, more preferably 0.3. It can be contained at -40 mg / g, more preferably 0.35-30 mg / g.
一方、従来の一般的な乳飲料、発酵乳では、脂質の1g当たり、リン脂質が20mgで含まれるが、本発明の乳飲料、発酵乳では、脂質の1g当たり、リン脂質が25~3000mgで含まれ、好ましくは30~2500mg、より好ましくは40~2000mg、さらに好ましくは、50~1500mgで含まれるものであることができる。また、本発明の飲食品または組成物では、脂質を少量で含む場合、スフィンゴミエリンが0.05~60mg/gで含まれ、好ましくは0.1~50mg/g、より好ましくは0.15~40mg/g、さらに好ましくは、0.2~30mg/gで含まれるものであることができる。 On the other hand, the conventional general milk drink and fermented milk contain 20 mg of phospholipid per gram of lipid, but the milk drink and fermented milk of the present invention contain 25 to 3000 mg of phospholipid per 1 g of lipid. It is preferably contained in an amount of 30 to 2500 mg, more preferably 40 to 2000 mg, and still more preferably 50 to 1500 mg. In addition, in the food or drink or composition of the present invention, when lipid is contained in a small amount, sphingomyelin is contained at 0.05 to 60 mg / g, preferably 0.1 to 50 mg / g, more preferably 0.15 to It can be contained at 40 mg / g, more preferably 0.2 to 30 mg / g.
そして、従来の一般的な乳飲料、発酵乳では、脂質の1g当たり、リン脂質が20mgで含まれるが、本発明の乳飲料、発酵乳では、脂質の1g当たり、リン脂質が25~3000mgで含まれ、好ましくは30~2500mg、より好ましくは40~2000mg、さらに好ましくは、50~1500mgで含まれるものであることができる。また、本発明の乳飲料、発酵乳、清涼飲料、ゼリー飲料、タブレット、美容用の粉末食品では、脂質を殆ど含まない(無脂肪の)場合、スフィンゴミエリンが0.02~60mg/gで含まれ、好ましくは0.04~50mg/g、より好ましくは0.06~40mg/g、さらに好ましくは、0.08~30mg/gで含まれるものであることができる。 The conventional general milk drink and fermented milk contain 20 mg of phospholipid per gram of lipid, but the milk drink and fermented milk of the present invention contain 25 to 3000 mg of phospholipid per 1 g of lipid. It is preferably contained in an amount of 30 to 2500 mg, more preferably 40 to 2000 mg, and still more preferably 50 to 1500 mg. In addition, in the milk beverage, fermented milk, soft drink, jelly beverage, tablet, and cosmetic powder food of the present invention, when containing almost no lipid (non-fat), sphingomyelin is contained at 0.02 to 60 mg / g. Preferably, it can be contained at 0.04 to 50 mg / g, more preferably 0.06 to 40 mg / g, and still more preferably 0.08 to 30 mg / g.
本発明の別の態様によれば、乳酸菌および/またはビフィズス菌の発酵物および/または培養物をスフィンゴ脂質と同時に、スフィンゴ脂質の摂取が望まれる対象に、経口摂取させるか、または経腸投与することを含む、スフィンゴ脂質の吸収促進方法が提供される。ここで、このましくは、スフィンゴ脂質はスフィンゴミエリンである。 According to another aspect of the present invention, a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria is orally administered or enterally administered to a subject who wants to take the sphingolipid simultaneously with the sphingolipid. A method for promoting the absorption of sphingolipids. Here, preferably, the sphingolipid is sphingomyelin.
本発明のさらに別の態様によれば、乳酸菌および/またはビフィズス菌の発酵物および/または培養物をスフィンゴ脂質と同時に、スフィンゴ脂質の摂取が望まれる対象に、経口摂取させるか、または経腸投与することを含む、セラミドの吸収促進方法が提供される。 According to still another aspect of the present invention, a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria is orally administered or enterally administered to a subject who wants to take sphingolipids simultaneously with sphingolipids. A method for promoting absorption of ceramide is provided.
なお、ここで、好ましくは、前記方法は、医療用途を除いたものである。また、前記の対象とは、好ましくは、ヒト、またはヒト以外の哺乳類である。 Note that, preferably, the above method excludes medical use. The subject is preferably a human or a non-human mammal.
そして、前記方法は、好ましくは乳酸菌および/またはビフィズス菌の発酵物および/または培養物を2日以上で継続して経口摂取させるか、または経腸投与する、スフィンゴ脂質の摂取が望まれる対象のためのスフィンゴ脂質の吸収促進方法、スフィンゴ脂質の摂取が望まれる対象のためのセラミドの吸収促進方法であることができる。 The method is preferably used for a subject in whom intake of sphingolipid is desired, wherein a fermented product and / or culture of lactic acid bacteria and / or bifidobacteria are continuously orally ingested for 2 days or more, or enterally administered. Therefore, it is possible to provide a method for promoting absorption of sphingolipids and a method for promoting absorption of ceramides for subjects in whom intake of sphingolipids is desired.
以下において、本発明を下記の実施例によって詳細に説明するが、本発明は、これらに限定されるものではない。 Hereinafter, the present invention will be described in detail with reference to the following examples, but the present invention is not limited thereto.
実施例1: ヨーグルトとスフィンゴミエリンの同時投与におけるスフィンゴミエリンの吸収性の評価試験
ラットに、乳由来のスフィンゴミエリンのみを投与するか、粉末のヨーグルトと乳由来のスフィンゴミエリンを同時に投与して、リンパ液中に取り込まれたスフィンゴミエリンの吸収量を評価した。
Example 1: Evaluation test of absorbability of sphingomyelin in simultaneous administration of yogurt and sphingomyelin To rats, only milk-derived sphingomyelin is administered, or powdered yogurt and milk-derived sphingomyelin are administered simultaneously, lymph The amount of sphingomyelin absorbed was evaluated.
[実験方法]
Sugawaraらの方法(J. Lipid Res. 2010, 51, 1761-1769)に従って実験した。具体的には、下記の通りであった。
[experimental method]
The experiment was conducted according to the method of Sugawara et al. (J. Lipid Res. 2010, 51, 1761-1769). Specifically, it was as follows.
(1-1) スフィンゴミエリンの投与およびリンパ液の回収
ラット(SD系、雄、体重:約350g)を1週間で馴化飼育した後に、胸管リンパと胃にカニュレを処置し、シリンジポンプを用いて、緩衝液(グルコース:139mM、塩化ナトリウム:85mM)を胃内へ一晩で(約12時間で)送液(流速:3mL/min)した。
(1-1) Administration of sphingomyelin and collection of lymph fluid Rats (SD strain, male, body weight: about 350 g) were acclimated and bred in 1 week, and then treated with cannula in the thoracic lymph and stomach using a syringe pump. Then, a buffer solution (glucose: 139 mM, sodium chloride: 85 mM) was fed into the stomach overnight (in about 12 hours) (flow rate: 3 mL / min).
そして、後述するような各試験溶液(A)、(B)および(C)に対応して、ラットを3群(a、b、c)に群分けし、これら各試験溶液を胃内に投与する1時間前から、3群(a、b、c)について、EDTA処理したスピッツ管にリンパ液を回収した。 Then, corresponding to each test solution (A), (B) and (C) as will be described later, the rats are divided into 3 groups (a, b, c), and these test solutions are administered into the stomach. From 1 hour before, lymph fluid was collected in Spitz tubes treated with EDTA for 3 groups (a, b, c).
さらに、シリンジポンプを用いて、各試験溶液(A)、(B)および(C)(各3mL)を胃内へ1分間で送液(流速:3mL/min)した後に、シリンジポンプを用いて、緩衝液を胃内へ6時間で送液(流速:3mL/min)した。 Furthermore, each test solution (A), (B), and (C) (each 3 mL) was sent into the stomach in 1 minute using a syringe pump (flow rate: 3 mL / min), and then the syringe pump was used. The buffer solution was fed into the stomach in 6 hours (flow rate: 3 mL / min).
そして、この1時間毎で、3群(a、b、c)について、EDTA処理したスピッツ管にリンパ液を回収した。 Then, every hour, lymph fluid was collected in Spitz tubes treated with EDTA for three groups (a, b, c).
(1-2) 試験溶液
各試験溶液(A)、(B)および(C)を下記のようにして調製した。
(A) トリオレイン:200mg、牛血清アルブミン:50mg、およびタウロコール酸ナトリウム:200mgを混合した。
(1-2) Test Solution Each test solution (A), (B) and (C) was prepared as follows.
(A) Triolein: 200 mg, bovine serum albumin: 50 mg, and sodium taurocholate: 200 mg were mixed.
(B) トリオレイン:195mg、牛血清アルブミン:50mg、およびタウロコール酸ナトリウム:200mgを混合した液体に、乳由来のスフィンゴミエリン(SM、純度98%、長良サイエンス社):5mgを超音波で乳化させた。 (B) Triolein: 195 mg, bovine serum albumin: 50 mg, and sodium taurocholate: 200 mg were mixed with milk-derived sphingomyelin (SM, purity 98%, Nagara Science Co., Ltd.): 5 mg ultrasonically emulsified. It was.
(C) トリオレイン:192mg、牛血清アルブミン:50mg、およびタウロコール酸ナトリウム200mgを混合した液体に、乳由来のスフィンゴミエリン(SM、純度98%、長良サイエンス社):4.75mgを超音波で乳化させた。これと合わせて、粉末のヨーグルト(YG、脂肪:約0%、明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手):250mgを用意した。
(C) Triolein: 192 mg, bovine serum albumin: 50 mg, and
(1-3) 評価群の構成
試験溶液(A)、(B)および(C)に対応した3群(a、b、c)を次に示し、それらの内容を表1に示した。なお、各群のラットを5匹ずつとした。
(a) 対照群: 試験溶液(A):3mL/rat(SM:0mg/rat)で胃内投与した。
(b) SM群: 試験溶液(B):3mL/rat(SM:5mg/rat)で胃内投与した。
(c) SM+YG群: 試験溶液(C):3mL/rat(SM:4.75mg/rat)と合わせて、YG:250mg/ratで胃内投与した。
(1-3) Structure of Evaluation Group Three groups (a, b, c) corresponding to the test solutions (A), (B), and (C) are shown below, and the contents thereof are shown in Table 1. The number of rats in each group was 5.
(A) Control group: Test solution (A): Intragastric administration at 3 mL / rat (SM: 0 mg / rat).
(B) SM group: Test solution (B): Intragastric administration at 3 mL / rat (SM: 5 mg / rat).
(C) SM + YG group: Test solution (C): 3 mL / rat (SM: 4.75 mg / rat) and YG: 250 mg / rat were intragastrically administered.
(1-4) 評価指標
試験溶液を投与した後に、ラットのリンパ液のスフィンゴミエリンの吸収量を評価した。具体的には、ラットのリンパ液には存在せず、乳由来のスフィンゴミエリンに特異的に存在するセラミド分子種(d16:1-C16:0)、スフィンゴミエリン分子種(d16:1-C16:0 SM)の動態を指標として、吸収性の違いを比較した。
(1-4) Evaluation index After administration of the test solution, the amount of sphingomyelin absorbed in the lymph of the rat was evaluated. Specifically, a ceramide molecular species (d16: 1-C16: 0) and a sphingomyelin molecular species (d16: 1-C16: 0) that are not present in rat lymph and are specifically present in milk-derived sphingomyelin. The difference in absorbability was compared using the kinetics of SM) as an index.
(1-5) 分析方法
ラットから採取したリンパ液の脂質の抽出は、Folchらの方法(J. Biol. Chem., 1957, 226, 497-509)に従った。
具体的には、リンパ液:200μL(リンパ液を2.5mL/hで回収した場合)に、生理食塩水:800μLを加えて、クロロホルム-メタノールの混合液(2:1(v/v)):4mLを加え、振とう(200rpm、15分間)した。次いで、遠心分離(2000rpm、10分間)した後に、下層を別のチューブに移し、遠心濃縮してから、メタノール:500μLを加えて、セラミドの分析用の試料を調製した。さらに、メタノールで10倍に希釈して、スフィンゴミエリンの分析用の試料を調製した。
(1-5) Analytical Method Extraction of lipids from lymph collected from rats was performed according to the method of Folch et al. (J. Biol. Chem., 1957, 226, 497-509).
Specifically, lymph: 200 μL (when lymph is collected at 2.5 mL / h), physiological saline: 800 μL is added, and a chloroform-methanol mixture (2: 1 (v / v)): 4 mL And shaken (200 rpm, 15 minutes). Next, after centrifugation (2000 rpm, 10 minutes), the lower layer was transferred to another tube and concentrated by centrifugation, and then 500 μL of methanol was added to prepare a sample for ceramide analysis. Furthermore, the sample for analysis of sphingomyelin was prepared by diluting 10 times with methanol.
標準品には、セラミド(d18:1-C16:0、Avanti polar lipids社より入手)、スフィンゴミエリン(d18:1-C16:0 SM、Avanti polar lipids社より入手)を用いた。これらの標準品を当量として、LC/MS/MS(ACQUITY premier XE (Waters社製))を用いて、セラミド(d16:1-C16:0)、スフィンゴミエリン(d16:1-C16:0 SM)を定量した。このとき、カラムには、ACQUITY UPLC BEH C18(2mm×100mm、Waters社製)を用い、移動相Aには、酢酸アンモニウム(5mM)/メタノール(95%)を、移動相Bには、酢酸アンモニウム(5mM)/メタノールを用いた。 As standard products, ceramide (d18: 1-C16: 0, obtained from Avanti Polar Lipids) and sphingomyelin (d18: 1-C16: 0 SM, obtained from Avanti Polar Lipids) were used. Using these standard products as equivalents, ceramide (d16: 1-C16: 0), sphingomyelin (d16: 1-C16: 0 SM) using LC / MS / MS (ACQUITY premier XE (Waters)) Was quantified. At this time, ACQUITY UPLC BEH C18 (2 mm × 100 mm, manufactured by Waters) was used for the column, ammonium acetate (5 mM) / methanol (95%) was used for mobile phase A, and ammonium acetate was used for mobile phase B. (5 mM) / methanol was used.
そして、移動相Aを100%から開始し、30分後に、移動相Bを100%になるようにグラジエントしてから、移動相Bを100%にして2分間で保持し、さらに3分後に、移動相Aが100%になるように切り替えた。ここで、LC/MS/MSにおける1試料の測定時間を35分間、移動相の流速を0.4mL/分、カラムの温度を40℃に設定し、エレクトロ・スプレー・イオン化を用いて、ポジティブモードで検出した。LC/MS/MSの分析変数として、キャピラリーの電圧を3000V、ソースの温度を120℃、脱溶媒の温度を400℃、脱溶媒ガスの流速を850L/時間、コーンガスの流速を50L/時間、コーン電圧を40V/時間に設定した。 Then, mobile phase A was started from 100%, and after 30 minutes, mobile phase B was gradiented to 100%, then mobile phase B was made 100% and held for 2 minutes, and after another 3 minutes, The mobile phase A was switched to 100%. Here, the measurement time of one sample in LC / MS / MS is set to 35 minutes, the flow rate of the mobile phase is set to 0.4 mL / min, the temperature of the column is set to 40 ° C., and electrospray ionization is used. Detected with. As analytical variables of LC / MS / MS, capillary voltage is 3000V, source temperature is 120 ° C, solvent removal temperature is 400 ° C, solvent removal gas flow rate is 850L / hour, cone gas flow rate is 50L / hour, cone The voltage was set at 40V / hour.
[結果]
結果は図1および図2に示されるとおりであった。
[result]
The results were as shown in FIG. 1 and FIG.
図1には、セラミド分子種(d16:1-C16:0)量の推移を示した。ここで、各試験溶液を経口投与してから4、5、6時間後に、SM群に比べて、SM+YG群において、セラミド分子種量は高値であった。
図2には、スフィンゴミエリン分子種(d16:1-C16:0 SM)量の推移を示した。ここで、各試験溶液を経口投与してから3、4、5、6時間後に、SM群に比べて、SM+YG群において、スフィンゴミエリン分子種量は高値であった。
FIG. 1 shows the transition of the amount of ceramide molecular species (d16: 1-C16: 0). Here, 4, 5, and 6 hours after oral administration of each test solution, the ceramide molecular species amount was higher in the SM + YG group than in the SM group.
FIG. 2 shows changes in the amount of sphingomyelin molecular species (d16: 1-C16: 0 SM). Here, 3, 4, 5, and 6 hours after oral administration of each test solution, the amount of sphingomyelin molecular species was higher in the SM + YG group than in the SM group.
これらの結果から、スフィンゴミエリンとヨーグルトを同時に経口摂取することにより、セラミドの吸収が促進されると共に、スフィンゴミエリンの吸収が促進されることがわかった。 From these results, it was found that simultaneous intake of sphingomyelin and yoghurt promotes absorption of ceramide and sphingomyelin.
実施例2: ヨーグルトと乳由来スフィンゴミエリン高含有リン脂質濃縮物(MPL)の同時摂取におけるスフィンゴミエリンの吸収性の評価試験
ラットに、MPLのみを経口投与するか、ヨーグルトとMPLを同時に経口投与するかして、血中のセラミド量を評価した。
Example 2: Evaluation test of absorbability of sphingomyelin in simultaneous intake of yogurt and milk-derived sphingomyelin-rich phospholipid concentrate (MPL) Oral administration of MPL alone or oral administration of yogurt and MPL simultaneously to rats Thus, the amount of ceramide in the blood was evaluated.
[実験方法]
(2-1) MPLの経口投与および採血
ラット(SD系、雄、体重:約300g)を1週間で馴化飼育した。そして、ラットを16時間で絶食させた後に、2群に群分けし、下記に示す各試験溶液(D)および(E)を経口投与し、その投与前、その投与の90分後、180分後、270分後、360分後に、尾静脈より採血した。そして、常法に従い、血清を得た。
[experimental method]
(2-1) Oral administration of MPL and blood collection Rats (SD strain, male, body weight: about 300 g) were bred and bred in one week. Then, after the rats were fasted for 16 hours, they were divided into two groups, and each of the test solutions (D) and (E) shown below was orally administered. Before the administration, 90 minutes after the administration, 180 minutes After 270 minutes and 360 minutes, blood was collected from the tail vein. Then, serum was obtained according to a conventional method.
(2-2) 評価群の構成
(d) MPL群: 試験溶液(D):体重の1kgあたり、MPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(e) MPL+YG群: 試験溶液(E):体重の1kgあたり、ヨーグルト(明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(2-2) Composition of Evaluation Group (d) MPL Group: Test Solution (D): MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
(E) MPL + YG group: Test solution (E): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight Was administered.
(2-3) 評価指標
試験溶液を経口投与した後に、ラット血清中のセラミド量を評価した。
具体的には、ラットの血清には存在せず、乳由来のスフィンゴミエリンに特異的に存在するセラミド分子種(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)の動態を指標として、血清濃度の違いを比較した。
(2-3) Evaluation index After the test solution was orally administered, the amount of ceramide in rat serum was evaluated.
Specifically, ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23) that are not present in rat serum but are specifically present in milk-derived sphingomyelin. : 0, d16: 1-C24: 0), and the difference in serum concentration was compared.
(2-4) 分析方法
ラットから採取した血清脂質の抽出は、Folchらの方法(J. Biol. Chem., 1957, 226, 497-509)に従った。
具体的には、血清:50μLに、生理食塩水:200μLを加えてから、クロロホルム-メタノールの混合液(2:1(v/v)):1mLを加え、抽出した。次いで、遠心分離(2000rpm、10分間)した後に、下層を別のチューブに移し、遠心濃縮してから、メタノール:200μLを加えて、セラミドの分析用の試料を調製した。
(2-4) Analytical method Extraction of serum lipids collected from rats was according to the method of Folch et al. (J. Biol. Chem., 1957, 226, 497-509).
Specifically, physiological saline: 200 μL was added to serum: 50 μL, followed by extraction with a chloroform-methanol mixture (2: 1 (v / v)): 1 mL. Next, after centrifugation (2000 rpm, 10 minutes), the lower layer was transferred to another tube and concentrated by centrifugation, and then methanol: 200 μL was added to prepare a sample for ceramide analysis.
標準品には、セラミド(d18:1-C16:0、d18:1-C22:0、d18:1-C23:0、d18:1-C24:0、Avanti polar lipids社より入手)を用いた。これらの標準品を当量として、LC/MS/MS(ACQUITY premier XE(Waters社製))を用い、セラミド(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)を定量した。このとき、カラムには、ACQUITY UPLC BEH C18(2mm×100mm、Waters社製)を用い、移動相Aには、酢酸アンモニウム(5mM)/メタノール(95%)を、移動相Bには、酢酸アンモニウム(5mM)/メタノールを用いた。 As a standard product, ceramide (d18: 1-C16: 0, d18: 1-C22: 0, d18: 1-C23: 0, d18: 1-C24: 0, obtained from Avanti Polar Lipids) was used. Using these standard products as equivalents, LC / MS / MS (ACQUITY premier XE (manufactured by Waters)) was used and ceramide (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0). At this time, ACQUITY UPLC BEH C18 (2 mm × 100 mm, manufactured by Waters) was used for the column, ammonium acetate (5 mM) / methanol (95%) was used for mobile phase A, and ammonium acetate was used for mobile phase B. (5 mM) / methanol was used.
そして、移動相Aを100%から開始し、30分後に、移動相Bを100%になるようにグラジエントしてから、移動相Bを100%にして2分間で保持し、さらに3分後に、移動相Aが100%になるように切り替えた。ここで、LC/MS/MSにおける1試料の測定時間を35分間、移動相の流速を0.4mL/分、カラムの温度を40℃に設定し、エレクトロ・スプレー・イオン化を用いて、ポジティブモードで検出した。LC/MS/MSの分析変数として、キャピラリーの電圧を3000V、ソースの温度を120℃、脱溶媒の温度を400℃、脱溶媒ガスの流速を850L/時間、コーンガスの流速を50L/時間、コーン電圧を40V/時間に設定した。 Then, mobile phase A was started from 100%, and after 30 minutes, mobile phase B was gradiented to 100%, then mobile phase B was made 100% and held for 2 minutes, and after another 3 minutes, The mobile phase A was switched to 100%. Here, the measurement time of one sample in LC / MS / MS is set to 35 minutes, the flow rate of the mobile phase is set to 0.4 mL / min, the temperature of the column is set to 40 ° C., and electrospray ionization is used. Detected with. As analytical variables of LC / MS / MS, capillary voltage is 3000V, source temperature is 120 ° C, solvent removal temperature is 400 ° C, solvent removal gas flow rate is 850L / hour, cone gas flow rate is 50L / hour, cone The voltage was set at 40V / hour.
[結果]
結果は図3および図4に示されるとおりであった。
[result]
The results were as shown in FIG. 3 and FIG.
図3には、血清セラミド分子種(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)量の変化を示した。セラミド分子種(d16:1-C16:0)では、試験溶液の投与後90、180分後、セラミド分子種(d16:1-C22:0、d16:1-C23:0)では、試験溶液の投与後90、180、270分後、セラミド分子種(d16:1-C24:0)では、試験溶液の投与後90、180、270、360分後に、MLP群に比べて、MPL+YG群において、有意に高値であった。 FIG. 3 shows changes in serum ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0). For ceramide molecular species (d16: 1-C16: 0), 90 and 180 minutes after administration of the test solution, and for ceramide molecular species (d16: 1-C22: 0, d16: 1-C23: 0), At 90, 180, and 270 minutes after administration, ceramide molecular species (d16: 1-C24: 0) were significantly more significant in the MPL + YG group than in the MLP group at 90, 180, 270, and 360 minutes after administration of the test solution. It was overpriced.
図4には、血清中のセラミド分子種量の時間曲線下面積を示した。いずれのセラミド分子種も、時間曲線下面積がMPL群に比べて、MPL+YG群において、有意に高値であった。 FIG. 4 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species were significantly higher in the MPL + YG group in the area under the time curve than in the MPL group.
スフィンゴミエリンを高含有に含む乳由来のリン脂質濃縮物とヨーグルトを同時に経口摂取することにより、スフィンゴミエリンの吸収が促進されることがわかった。 It was found that the absorption of sphingomyelin was promoted by simultaneously ingesting a milk-derived phospholipid concentrate and yogurt containing a high content of sphingomyelin.
実施例3: 紫外線の照射下における皮膚のバリア機能の悪化に対するヨーグルトとスフィンゴ脂質の影響
紫外線を照射することによって、皮膚のバリア機能を悪化させたヘアレスマウスに、スフィンゴミエリンまたは、スフィンゴミエリンとヨーグルトを3日間経口摂取させて、皮膚バリア機能(角層水分量、経皮水分蒸散量(TEWL))への影響を評価した。
スフィンゴ脂質として、乳由来のスフィンゴミエリン(SM、純度98%、長良サイエンス社)を使用した。
Example 3: Effect of yogurt and sphingolipid on deterioration of skin barrier function under irradiation of ultraviolet rays Hairless mice whose skin barrier function was deteriorated by irradiation with ultraviolet rays were treated with sphingomyelin or sphingomyelin and yogurt. It was orally ingested for 3 days, and the influence on the skin barrier function (the amount of stratum corneum moisture, the amount of transdermal moisture transpiration (TEWL)) was evaluated.
As the sphingolipid, milk-derived sphingomyelin (SM, purity 98%, Nagara Science) was used.
[実験方法]
(3-1) 紫外線の照射による皮膚のバリア機能悪化状態の誘導
ヘアレスマウス(Hos:HR-1、雌、4週齢 星野試験動物飼育所)を1週間で馴化させた後に、20mJ/cm2の条件で、紫外線(UV-B(GL20SE、三共電気株式会社))を照射した。
[experimental method]
(3-1) Induction of deterioration of skin barrier function by ultraviolet irradiation Hairless mice (Hos: HR-1, female, 4 weeks old Hoshino Test Animal Breeding) were acclimatized for 1 week, and then 20 mJ / cm 2 Under the conditions, ultraviolet rays (UV-B (GL20SE, Sankyo Electric Co., Ltd.)) were irradiated.
(3-2) 評価群の構成
皮膚のバリア機能悪化の試験系を用いて、スフィンゴミエリンまたはスフィンゴミエリンとヨーグルトの経口投与による皮膚の状態への影響を評価した。各群の試験系を8匹ずつとした。動物実験の群構成(評価群の構成)とスフィンゴミエリンとヨーグルトの含量の関係を、下記に示した。
(3-2) Composition of Evaluation Group Using a test system for deterioration of the skin barrier function, the effect of sphingomyelin or sphingomyelin and yogurt on the skin condition was evaluated. There were 8 test systems in each group. The relationship between the group configuration of the animal experiment (configuration of the evaluation group) and the contents of sphingomyelin and yogurt is shown below.
Control群(対照群): 通常飼料を摂取する群
SM群: スフィンゴミエリンを10mg/kg/dayで経口投与する群
SM+YG群: スフィンゴミエリンとヨーグルトをそれぞれ10mg/kg/day、11.3g/kg/dayで経口投与する群
(ただし、前記SM群とSM+YG群では共に、スフィンゴミエリンやヨーグルトに加えて、さらにコラーゲンを1000mg/kg/dayの割合で経口投与している)。
Control group (control group): group in which normal feed is ingested SM group: group in which sphingomyelin is orally administered at 10 mg / kg / day SM + YG group: sphingomyelin and yoghurt in 10 mg / kg / day, 11.3 g / kg / A group to be orally administered on day (however, in the SM group and SM + YG group, collagen is further orally administered at a rate of 1000 mg / kg / day in addition to sphingomyelin and yogurt).
(3-3) 評価試験方法
各試験群について、角層水分量およびTEWLを測定し、これらより、皮膚のバリア機能を評価した。
(3-3) Evaluation Test Method For each test group, the stratum corneum water content and TEWL were measured, and the barrier function of the skin was evaluated from these.
(3-3-1) 角層水分量
角層水分量は、コルネオメーター(Corneometer,Courage and Khazaka Electronic GmbH社)を用いて、5回/匹で測定した。このうち、最大値と最小値を除いた3回の測定値の平均を採用し、角層水分量とした。
(3-3-1) Water content of the stratum corneum The water content of the stratum corneum was measured 5 times / animal using a Corneometer (Corneometer, Curage and Khazaka Electronic GmbH). Among these, the average of three measurement values excluding the maximum value and the minimum value was adopted to obtain the stratum corneum moisture content.
(3-3-2) 経皮水分蒸散量(TEWL)
経皮水分蒸散量(TEWL)は、テヴァメーター(Tewemeter MPA580,Courage and Khazaka Electronic GmbH社)に、29℃に保温したプローブを20秒間で用いて測定した。これら得られた測定結果について、3回の平均を採用、経皮水分蒸散量とした。
(3-3-2) Transdermal moisture transpiration (TEWL)
Transcutaneous moisture transpiration (TEWL) was measured with a tevameter (Tewemeter MPA580, Curage and Khazaka Electronic GmbH) using a probe kept at 29 ° C. for 20 seconds. About the obtained measurement result, the average of 3 times was employ | adopted and it was set as the amount of transdermal moisture transpiration.
[評価結果]
(角層水分量)
結果は、図5に示した通りであった。
図5において、Control群の角層水分量に比べて、SM群およびSM+YG群の角層水分量は高値であった。さらに、SM+YG群はSM群に比べ、高値であった。このことから、SM+YG群は、SM群に比べて皮膚のバリア機能の悪化がより抑制(改善)されたと考えられた。
[Evaluation results]
(Corn layer moisture content)
The result was as shown in FIG.
In FIG. 5, the stratum corneum moisture content of the SM group and the SM + YG group was higher than the stratum corneum moisture content of the Control group. Furthermore, the SM + YG group was higher than the SM group. From this, it was considered that the SM + YG group suppressed (improved) the deterioration of the skin barrier function more than the SM group.
(経皮水分蒸散量(TEWL))
結果は、図6に示した通りであった。
図6において、Control群のTEWLに比べて、SM群のTEWLは低値であった。さらに、SM+YG群はSM群に比べ、低値であった。これらから、SM+YG群は、SM群に比べて皮膚のバリア機能の悪化がより抑制(改善)されたと考えられた。
(Transdermal moisture transpiration (TEWL))
The result was as shown in FIG.
In FIG. 6, the TE group's TEWL was lower than the control group's TEWL. Further, the SM + YG group was lower than the SM group. From these, it was considered that in the SM + YG group, the deterioration of the skin barrier function was further suppressed (improved) compared to the SM group.
スフィンゴ脂質とヨーグルト(発酵乳)を経口摂取することで、紫外線に基づく皮膚のバリア機能の悪化がより抑制(改善)されることが示唆された。さらに、スフィンゴミエリンとヨーグルト(発酵乳)を3日間以上で継続して摂取する程、皮膚のバリア機能の悪化が抑制(改善)されやすいことが示唆された。 It was suggested that oral intake of sphingolipid and yogurt (fermented milk) further suppresses (improves) the deterioration of the skin barrier function based on ultraviolet rays. Furthermore, it was suggested that the deterioration of the barrier function of the skin is more likely to be suppressed (improved) as the sphingomyelin and yoghurt (fermented milk) are continuously ingested over 3 days.
実施例4: 未発酵乳とMPLの同時摂取におけるスフィンゴミエリンの吸収性の評価試験
ラットに、MPLのみを経口投与した場合、ヨーグルトとMPLを同時に経口投与した場合、および、未発酵乳とMPLを同時に経口投与した場合のそれぞれについて、血中のセラミド量を評価した。
Example 4: Evaluation test of absorption of sphingomyelin in simultaneous intake of unfermented milk and MPL When rats were orally administered with MPL alone, when yogurt and MPL were orally administered simultaneously, and with unfermented milk and MPL The amount of ceramide in the blood was evaluated for each case of simultaneous oral administration.
[実験方法]
(4-1)
ラット(SD系、雄、体重:約270g)を1週間で馴化飼育した。そして、ラットを16時間で絶食させた後に、3群に群分けし、下記に示す試験溶液(F)、(G)および(H)を経口投与した。次いで、投与前、投与の90分後、180分後、270分後、および360分後の各タイミングに、尾静脈より採血を行い、常法に従い、血清を得た。
[experimental method]
(4-1)
Rats (SD strain, male, body weight: about 270 g) were acclimated and bred in one week. Then, after the rats were fasted for 16 hours, they were divided into three groups, and the test solutions (F), (G) and (H) shown below were orally administered. Next, blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after administration, and serum was obtained according to a conventional method.
(4-2)評価群の構成
(f)MPL群: 試験溶液(F):体重の1kgあたり、MPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(g)MPL+YG群: 試験溶液(G):体重の1kgあたり、ヨーグルト(明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(h)MPL+未発酵乳群: 試験溶液(H):体重の1kgあたり、脱脂粉乳(明治脱脂粉乳、株式会社明治より入手):1.3g、およびMPL:537mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(4-2) Composition of evaluation group (f) MPL group: Test solution (F): MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
(G) MPL + YG group: Test solution (G): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight Was administered.
(H) MPL + unfermented milk group: Test solution (H): skim milk powder (Meiji skim milk powder, obtained from Meiji Co., Ltd.): 1.3 g and MPL: 537 mg (100 mg as the total amount of sphingomyelin) per kg of body weight The dose of was administered.
(4―3)評価指標
試験溶液を経口投与した後に、ラット血清中のセラミド量を評価した。
具体的には、セラミド分子種(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)を指標とした。
(4-3) Evaluation index After the test solution was orally administered, the amount of ceramide in rat serum was evaluated.
Specifically, ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0) were used as indices.
[結果]
結果は、図7に示されるとおりであった。
[result]
The result was as shown in FIG.
図7では、血清中のセラミド分子種量の時間曲線下面積を示した。いずれのセラミド分子種も、時間曲線下面積がMPL群に比べて、MPL群、MPL+未発酵乳群、MPL+YG群の順に有意に高値になった。 FIG. 7 shows the area under the time curve of the amount of ceramide molecular species in serum. As for any ceramide molecular species, the area under the time curve was significantly higher in the order of the MPL group, the MPL + unfermented milk group, and the MPL + YG group in comparison with the MPL group.
スフィンゴミエリンを高含有に含む乳由来のリン脂質濃縮物と未発酵乳を同時に経口摂取することにより、スフィンゴミエリンの吸収が促進されるが、スフィンゴミエリンを高含有に含む乳由来のリン脂質濃縮物とヨーグルトを同時に経口摂取することにより、さらにスフィンゴミエリンの吸収が促進されることがわかった。 Absorption of sphingomyelin is promoted by simultaneous ingestion of milk-derived phospholipid concentrate and non-fermented milk at a high content of sphingomyelin, but milk-derived phospholipid concentrate at a high content of sphingomyelin It was found that the simultaneous intake of yogurt and yogurt further promotes the absorption of sphingomyelin.
実施例5: ヨーグルト分画物とMPLの同時摂取におけるスフィンゴミエリンの吸収性の評価試験
ラットに、MPLのみを経口投与した場合、ヨーグルトとMPLを同時に経口投与した場合、ヨーグルト分画上清物とMPLを同時に経口投与した場合、およびヨーグルト分画沈殿物とMPLを同時に経口投与した場合のそれぞれについて、血中のセラミド量を評価した。
Example 5: Evaluation test of absorption of sphingomyelin in simultaneous intake of yogurt fraction and MPL When rats were orally administered with MPL alone, yogurt and MPL were orally administered simultaneously, yogurt fraction supernatant and The amount of ceramide in blood was evaluated when MPL was orally administered at the same time and when yogurt fraction precipitate and MPL were orally administered at the same time.
[実験方法]
(5-1)ヨーグルト分画物の調製方法
ヨーグルト(明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手)を6000rpmで10分間遠心分離し、ヨーグルト分画上清物およびヨーグルト分画沈殿物を得た。
[experimental method]
(5-1) Preparation Method of Yogurt Fraction Yogurt (Meiji Bulgaria Yogurt Fat Zero, obtained from Meiji Co., Ltd.) was centrifuged at 6000 rpm for 10 minutes to obtain a yogurt fraction supernatant and a yogurt fraction precipitate. .
(5-2)
ラット(SD系、雄、体重:約270g)を1週間で馴化飼育した。そして、ラットを16時間で絶食させた後に、3群に群分けし、下記に示す試験溶液(I)、(J)および(K)および(L)を経口投与した。次いで、投与前、投与の90分後、180分後、270分後、および360分後の各タイミングに、尾静脈より採血を行い、常法に従い、血清を得た。
(5-2)
Rats (SD strain, male, body weight: about 270 g) were acclimated and bred in one week. Then, after the rats were fasted for 16 hours, they were divided into 3 groups, and test solutions (I), (J), (K) and (L) shown below were orally administered. Next, blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after administration, and serum was obtained according to a conventional method.
(5-3)評価群の構成
(i)MPL群: 試験溶液(I):体重の1kgあたり、MPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(j)MPL+YG群: 試験溶液(J):体重の1kgあたり、ヨーグルト(明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(k)MPL+YG上清群: 試験溶液(J):体重の1kgあたり、ヨーグルト上清:743mg、およびMPL:539mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(l)MPL+YG沈殿群: 試験溶液(K):体重の1kgあたり、ヨーグルト沈殿:455mg、およびMPL:536mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(5-3) Composition of Evaluation Group (i) MPL Group: Test Solution (I): MPL: 540 mg (100 mg as sphingomyelin) was administered per 1 kg of body weight.
(J) MPL + YG group: Test solution (J): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight Was administered.
(K) MPL + YG supernatant group: Test solution (J): Yogurt supernatant: 743 mg and MPL: 539 mg (100 mg as the total amount of sphingomyelin) were administered per kg of body weight.
(L) MPL + YG precipitation group: Test solution (K): Yogurt precipitation: 455 mg and MPL: 536 mg (100 mg as the total amount of sphingomyelin) were administered per 1 kg of body weight.
(5―4)評価指標
試験溶液を経口投与した後に、ラット血清中のセラミド量を評価した。
具体的には、セラミド分子種(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)を指標とした。
(5-4) Evaluation index After the test solution was orally administered, the amount of ceramide in rat serum was evaluated.
Specifically, ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0) were used as indices.
[結果]
結果は、図8に示されるとおりであった。
[result]
The result was as shown in FIG.
図8では、血清中のセラミド分子種量の時間曲線下面積を示した。いずれのセラミド分子種も、時間曲線下面積がMPL群に比べて、MPL+YG群およびMPL+YG上清群において、有意に高値であったが、MPL群とMPL+YG沈殿群の間に有意な差はみられなかった。 FIG. 8 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species had significantly higher areas under the time curve in the MPL + YG group and MPL + YG supernatant group than in the MPL group, but there was a significant difference between the MPL group and the MPL + YG precipitation group. There wasn't.
スフィンゴミエリンを高含有に含む乳由来のリン脂質濃縮物とヨーグルトの上清画分を同時に経口摂取することにより、スフィンゴミエリンの吸収が促進されることがわかった。これらの結果は、ヨーグルトの上清画分にスフィンゴミエリンの吸収を促進させる成分が含まれていることを示していると考えられた。 It was found that absorption of sphingomyelin was promoted by orally ingesting a milk-derived phospholipid concentrate containing a high content of sphingomyelin and a supernatant fraction of yogurt at the same time. These results were considered to indicate that the yogurt supernatant fraction contains a component that promotes the absorption of sphingomyelin.
実施例6: 乳酸とMPLの同時摂取におけるスフィンゴミエリンの吸収性の評価試験
ラットに、MPLのみを経口投与した場合、ヨーグルトとMPLを同時に経口投与した場合、および乳酸とMPLを同時に経口投与した場合のそれぞれについて、血中のセラミド量を評価した。
Example 6: Evaluation test of absorption of sphingomyelin in simultaneous intake of lactic acid and MPL When MPL alone was orally administered to rats, yogurt and MPL were orally administered simultaneously, and lactic acid and MPL were orally administered simultaneously For each of these, the amount of ceramide in the blood was evaluated.
[実験方法]
(6-1)
ラット(SD系、雄、体重:約270g)を1週間で馴化飼育した。そして、ラットを16時間で絶食させた後に、3群に群分けし、下記に示す試験溶液(L)、(M)および(N)を経口投与した。次いで、投与前、投与の90分後、180分後、270分後、および360分後の各タイミングに、尾静脈より採血を行い、常法に従い、血清を得た。
[experimental method]
(6-1)
Rats (SD strain, male, body weight: about 270 g) were acclimated and bred in one week. Then, after the rats were fasted for 16 hours, they were divided into 3 groups, and the test solutions (L), (M) and (N) shown below were orally administered. Next, blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after administration, and serum was obtained according to a conventional method.
(6-2)評価群の構成
(l)MPL群: 試験溶液(L):体重の1kgあたり、MPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(m)MPL+YG群: 試験溶液(M):体重の1kgあたり、ヨーグルト(明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(n)MPL+乳酸群: 試験溶液(N):体重の1kgあたり、乳酸(和光純薬工業株式会社より入手):109mg(ヨーグルト中の乳酸量とpHを等しくした)、およびMPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(6-2) Composition of Evaluation Group (l) MPL Group: Test solution (L): MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
(M) MPL + YG group: Test solution (M): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight Was administered.
(N) MPL + lactic acid group: Test solution (N): Lactic acid (obtained from Wako Pure Chemical Industries, Ltd.) per kg of body weight: 109 mg (the amount of lactic acid in yogurt was equal to the pH), and MPL: 540 mg (sphingo A dose of 100 mg) was administered as myelin.
(6―3)評価指標
試験溶液を経口投与した後に、ラット血清中のセラミド量を評価した。
具体的には、セラミド分子種(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)を指標とした。
(6-3) Evaluation index After the test solution was orally administered, the amount of ceramide in rat serum was evaluated.
Specifically, ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0) were used as indices.
[結果]
結果は、図9に示されるとおりであった。
[result]
The result was as shown in FIG.
図9では、血清中のセラミド分子種量の時間曲線下面積を示した。いずれのセラミド分子種も、時間曲線下面積がMPL群に比べて、MPL+YG群において、有意に高値であったが、MPL群とMPL+乳酸群の間に有意な差が見られなかった。 FIG. 9 shows the area under the time curve of the amount of ceramide molecular species in serum. For all ceramide molecular species, the area under the time curve was significantly higher in the MPL + YG group than in the MPL group, but no significant difference was observed between the MPL group and the MPL + lactic acid group.
これらの結果は、ヨーグルト中の乳酸はスフィンゴミエリンの吸収を促進させる成分でないことを示していると考えられた。 These results were considered to indicate that lactic acid in yogurt is not a component that promotes the absorption of sphingomyelin.
実施例7: ホエイたんぱく質とMPLの同時摂取におけるスフィンゴミエリンの吸収性の評価試験
ラットに、MPLのみを経口投与した場合、ヨーグルトとMPLを同時に経口投与した場合、およびホエイたんぱく質とMPLを同時に経口投与した場合のそれぞれについて、血中のセラミド量を評価した。
Example 7: Evaluation test of absorption of sphingomyelin in simultaneous intake of whey protein and MPL When rats were orally administered MPL alone, yogurt and MPL were orally administered simultaneously, and whey protein and MPL were orally administered simultaneously In each case, the amount of ceramide in the blood was evaluated.
[実験方法]
(7-1)
ラット(SD系、雄、体重:約270g)を1週間で馴化飼育した。そして、ラットを16時間で絶食させた後に、3群に群分けし、下記に示す試験溶液(O)、(P)および(Q)を経口投与た。次いで、投与前、投与の90分後、180分後、270分後、および360分後の各タイミングに、尾静脈より採血を行い、常法に従い、血清を得た。
[experimental method]
(7-1)
Rats (SD strain, male, body weight: about 270 g) were acclimated and bred in one week. Then, after the rats were fasted for 16 hours, they were divided into 3 groups, and test solutions (O), (P) and (Q) shown below were orally administered. Next, blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after administration, and serum was obtained according to a conventional method.
(7-2)評価群の構成
(o)MPL群: 試験溶液(O):体重の1kgあたり、MPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(p)MPL+YG群: 試験溶液(P):体重の1kgあたり、ヨーグルト(明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(q)MPL+ホエイたんぱく質群: 試験溶液(Q):体重の1kgあたり、ホエイたんぱく質(アラセン8899、フォンテラ社より入手):109mg(ヨーグルト中のホエイたんぱく質量と等しくした)、およびMPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(7-2) Composition of Evaluation Group (o) MPL Group: Test Solution (O): MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
(P) MPL + YG group: Test solution (P): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as total amount of sphingomyelin) per kg of body weight Was administered.
(Q) MPL + whey protein group: Test solution (Q): Whey protein (Aracene 8899, obtained from Fontera) per kg of body weight: 109 mg (equal to the weight of whey protein in yogurt), and MPL: 540 mg (sphingo A dose of 100 mg) was administered as myelin.
(7―3)評価指標
試験溶液を経口投与した後に、ラット血清中のセラミド量を評価した。
具体的には、セラミド分子種(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)を指標とした。
(7-3) Evaluation index After the test solution was orally administered, the amount of ceramide in rat serum was evaluated.
Specifically, ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0) were used as indices.
[結果]
結果は、図10に示されるとおりであった。
[result]
The result was as shown in FIG.
図10では、血清中のセラミド分子種量の時間曲線下面積を示した。いずれのセラミド分子種も、時間曲線下面積がMPL群に比べて、MPL+YG群において、有意に高値であったが、MPL群とMPL+ホエイたんぱく質群の間に有意な差はみられなかった。 FIG. 10 shows the area under the time curve of the amount of ceramide molecular species in serum. For all ceramide molecular species, the area under the time curve was significantly higher in the MPL + YG group than in the MPL group, but there was no significant difference between the MPL group and the MPL + whey protein group.
これらの結果は、ヨーグルト中のホエイたんぱく質はスフィンゴミエリンの吸収を促進させる成分でないことを示していると考えられた。 These results were considered to indicate that the whey protein in yogurt is not a component that promotes the absorption of sphingomyelin.
実施例8: 多糖類とMPLの同時摂取におけるスフィンゴミエリンの吸収性の評価試験
ラットに、MPLのみを経口投与した場合、ヨーグルトとMPLを同時に経口投与した場合、および多糖類とMPLを同時に経口投与した場合のそれぞれについて、血中のセラミド量を評価した。
Example 8 Evaluation Test of Sphingomyelin Absorption by Simultaneous Intake of Polysaccharide and MPL When rats are orally administered with MPL alone, yogurt and MPL are orally administered simultaneously, and polysaccharide and MPL are orally administered simultaneously In each case, the amount of ceramide in the blood was evaluated.
[実験方法]
(8-1)多糖類の精製
多糖類の精製はCerningらの方法(J. Dairy Sci., 1992, 75, 692-699)に従った。ヨーグルト上清画分をプロナーゼ(ロシュ製)処理し、たんぱく質を加水分解した。3倍量のエタノールを添加し、一晩冷凍し、遠心分離により多糖類を含む沈殿物を得た。沈殿物を限外ろ過膜(Merck Millipore, Centriprep Ultracel YM-3)により、たんぱく質加水分解物を除去し、多糖類を精製した。
[experimental method]
(8-1) Purification of polysaccharides Purification of polysaccharides was according to the method of Cerning et al. (J. Dairy Sci., 1992, 75, 692-699). The yogurt supernatant fraction was treated with pronase (Roche) to hydrolyze the protein. Three times the amount of ethanol was added, frozen overnight, and a precipitate containing polysaccharides was obtained by centrifugation. Protein precipitate was removed from the precipitate with an ultrafiltration membrane (Merck Millipore, Centriprep Ultracel YM-3), and the polysaccharide was purified.
(8-2)
ラット(SD系、雄、体重:約270g)を1週間で馴化飼育した。そして、ラットを16時間で絶食させた後に、3群に群分けし、下記に示す試験溶液(R)、(S)および(T)を経口投与した。次いで、投与前、その投与の90分後、180分後、270分後、および360分後の各タイミングに、尾静脈より採血を行い、常法に従い、血清を得た。
(8-2)
Rats (SD strain, male, body weight: about 270 g) were acclimated and bred in one week. Then, after the rats were fasted for 16 hours, they were divided into 3 groups, and the test solutions (R), (S) and (T) shown below were orally administered. Subsequently, blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after the administration, and serum was obtained according to a conventional method.
(8-3)評価群の構成
(r)MPL群: 試験溶液(R):体重の1kgあたり、MPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(s)MPL+YG群: 試験溶液(S):体重の1kgあたり、ヨーグルト(明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(t)MPL+多糖類群: 試験溶液(T):体重の1kgあたり、多糖類:52.5mg(ヨーグルト中の多糖類と等しくした)、およびMPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(8-3) Composition of evaluation group (r) MPL group: Test solution (R): MPL: 540 mg (100 mg as sphingomyelin) was administered per kg of body weight.
(S) MPL + YG group: Test solution (S): Dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and MPL: 535 mg (100 mg as the total amount of sphingomyelin) per kg of body weight Was administered.
(T) MPL + polysaccharide group: Test solution (T): administration of polysaccharide: 52.5 mg (equal to polysaccharide in yogurt) and MPL: 540 mg (100 mg as sphingomyelin) per kg body weight did.
(8―4)評価指標
試験溶液を経口投与した後に、ラット血清中のセラミド量を評価した。
具体的には、セラミド分子種(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)を指標とした。
(8-4) Evaluation index After the test solution was orally administered, the amount of ceramide in rat serum was evaluated.
Specifically, ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0) were used as indices.
[結果]
結果は、図11に示されるとおりであった。
[result]
The result was as shown in FIG.
図11には、血清中のセラミド分子種量の時間曲線下面積を示した。いずれのセラミド分子種も、時間曲線下面積がMPL群に比べて、MPL+YG群およびMPL+多糖類群において、有意に高値であった。 FIG. 11 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species were significantly higher in the area under the time curve in the MPL + YG group and the MPL + polysaccharide group than in the MPL group.
スフィンゴミエリンを高含有に含む乳由来のリン脂質濃縮物とヨーグルト中の多糖類を同時に経口摂取することにより、スフィンゴミエリンの吸収が促進され、ヨーグルト中の多糖類がスフィンゴミエリンの吸収を促進させる成分の一つであることを示していると考えられた。 A component that promotes absorption of sphingomyelin by simultaneously ingesting a phospholipid concentrate derived from milk containing a high content of sphingomyelin and a polysaccharide in yogurt, and the polysaccharide in yogurt promotes the absorption of sphingomyelin It was thought that it was one of.
実施例9: 乳酸菌および/またはビフィズス菌により調製されたヨーグルトとMPLの同時摂取におけるスフィンゴミエリンの吸収性の評価試験
ラットに、MPLのみを経口投与した場合、乳酸菌および/またはビフィズス菌により調製されたヨーグルトとMPLを同時に経口投与した場合のそれぞれについて、血中のセラミド量を評価した。
Example 9: Evaluation test of absorption of sphingomyelin in simultaneous intake of yogurt and MPL prepared by lactic acid bacteria and / or bifidobacteria When MPL alone was orally administered to rats, it was prepared by lactic acid bacteria and / or bifidobacteria The amount of ceramide in blood was evaluated for each of the cases where yogurt and MPL were orally administered simultaneously.
(9-1)
ラット(SD系、雄、体重:約270g)を1週間で馴化飼育した。そして、ラットを16時間で絶食させた後に、3群に群分けし、下記に示す試験溶液(U)、(V)、(W)、(X)および(Y)を経口投与した。次いで、投与前、その投与の90分後、180分後、270分後、および360分後の各タイミングに、尾静脈より採血を行い、常法に従い、血清を得た。
(9-1)
Rats (SD strain, male, body weight: about 270 g) were acclimated and bred in one week. Then, after the rats were fasted for 16 hours, the rats were divided into 3 groups, and the test solutions (U), (V), (W), (X) and (Y) shown below were orally administered. Subsequently, blood was collected from the tail vein at each timing before administration, 90 minutes, 180 minutes, 270 minutes, and 360 minutes after the administration, and serum was obtained according to a conventional method.
(9-2)評価群の構成
(u)MPL群: 試験溶液(U):体重の1kgあたり、MPL:540mg(スフィンゴミエリンとして100mg)の用量を投与した。
(v)MPL+YG(1)群: 試験溶液(V):体重の1kgあたり、ヨーグルト(1)(乳酸菌Lactobacillus GasseriおよびStreptococcus thermophilusにより調製、明治プロビオヨーグルトLG21脂肪ゼロ、株式会社明治より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(w)MPL+YG(2)群: 試験溶液(W):体重の1kgあたり、ヨーグルト(2)(乳酸菌Lactobacillus delbrueckii subsp. bulgaricusおよびStreptococcus thermophilusにより調製、明治プロビオヨーグルトR-1脂肪ゼロ、株式会社明治より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(x)MPL+YG(3)群: 試験溶液(W):体重の1kgあたり、ヨーグルト(3)(乳酸菌Lactobacillus Gasseri、ビフィズス菌Bifidobacterium longumにより調製、ナチュレ恵 megumi脂肪0(ゼロ)、雪印メグミルク株式会社より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(y)MPL+YG(4)群: 試験溶液(Y):体重の1kgあたり、ヨーグルト(4)(ビフィズス菌 Bifidobacterium longumにより調製、ビヒダスBB536プレーンヨーグルト脂肪ゼロ、森永乳業株式会社より入手):11.3g、およびMPL:535mg(スフィンゴミエリンの総量として100mg)の用量を投与した。
(9-2) Composition of Evaluation Group (u) MPL Group: Test Solution (U): MPL: 540 mg (100 mg as sphingomyelin) was administered per 1 kg of body weight.
(V) MPL + YG (1) group: Test solution (V): Yogurt per kg of body weight (1) (prepared by lactic acid bacteria Lactobacillus Gasseri and Streptococcus thermophilus, Meiji Probio Yogurt LG21 Fat Zero, obtained from Meiji Co., Ltd.): A dose of 3 g and MPL: 535 mg (100 mg as the total amount of sphingomyelin) was administered.
(W) MPL + YG (2) group: Test solution (W): per 1 kg of body weight, yogurt (2) (prepared by lactic acid bacteria Lactobacillus delbrueckii subsp. Bulgaricus and Streptococcus thermophilus, Meiji Probio Yogurt R-1 Fat Zero, Meiji Co., Ltd. Obtained): A dose of 11.3 g and MPL: 535 mg (100 mg total sphingomyelin) was administered.
(X) MPL + YG (3) group: Test solution (W): Yogurt per kg of body weight (3) (prepared by lactic acid bacteria Lactobacillus Gasseri, bifidobacteria Bifidobacterium longum, from Nature Megumi fat 0 (zero), Snow Brand Megmilk Co., Ltd. Obtained): A dose of 11.3 g and MPL: 535 mg (100 mg total sphingomyelin) was administered.
(Y) MPL + YG (4) group: Test solution (Y): Yogurt per kg of body weight (4) (prepared by Bifidobacterium longum, bihidas BB536 plain yogurt fat zero, obtained from Morinaga Milk Industry Co., Ltd.): 11.3 g , And MPL: 535 mg (100 mg total sphingomyelin) was administered.
(9―3)評価指標
試験溶液を経口投与した後に、ラット血清中のセラミド量を評価した。
具体的には、セラミド分子種(d16:1-C16:0、d16:1-C22:0、d16:1-C23:0、d16:1-C24:0)を指標とした。
(9-3) Evaluation index After the test solution was orally administered, the amount of ceramide in rat serum was evaluated.
Specifically, ceramide molecular species (d16: 1-C16: 0, d16: 1-C22: 0, d16: 1-C23: 0, d16: 1-C24: 0) were used as indices.
[結果]
結果は、図12に示されるとおりであった。
[result]
The result was as shown in FIG.
図12では、血清中のセラミド分子種量の時間曲線下面積を示した。いずれのセラミド分子種も、時間曲線下面積がMPL群に比べて、MPL+YG(1)群、MPL+YG(2)群、MPL+YG(3)群、MPL+YG(4)群において、有意に高値であった。 FIG. 12 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species had significantly higher areas in the MPL + YG (1) group, the MPL + YG (2) group, the MPL + YG (3) group, and the MPL + YG (4) group as compared to the MPL group.
スフィンゴミエリンを高含有に含む乳由来のリン脂質濃縮物と様々な乳酸菌および/またはビフィズス菌によって調製されたヨーグルトを同時に経口摂取することにより、スフィンゴミエリンの吸収が促進されることを示していると考えられた。 Ingestion of milk-containing phospholipid concentrate with high content of sphingomyelin and yogurt prepared by various lactic acid bacteria and / or bifidobacteria simultaneously indicates that absorption of sphingomyelin is promoted it was thought.
実施例10: ヨーグルトとグルコシルセラミドの同時摂取におけるグルコシルセラミドの吸収性の評価試験
ラットに、グルコシルセラミド(GC)のみを経口投与した場合、ヨーグルトとグルコシルセラミドLを同時に経口投与した場合のそれぞれについて、血中のセラミド量を評価した。
Example 10: Evaluation test of absorption of glucosylceramide in simultaneous intake of yogurt and glucosylceramide When glucosylceramide (GC) alone was orally administered to a rat, each of cases where yogurt and glucosylceramide L were orally administered simultaneously, The amount of ceramide in the blood was evaluated.
[実験方法]
(10-1)
ラット(SD系、雄、体重:約270g)を1週間で馴化飼育した。そして、ラットを16時間で絶食させた後に、3群に群分けし、下記に示す試験溶液(Y)および(Z)を経口投与した場合、投与前、投与の90分後、180分後、270分後、および360分後の各タイミングに、尾静脈より採血を行い、常法に従い、血清を得た。
[experimental method]
(10-1)
Rats (SD strain, male, body weight: about 270 g) were acclimated and bred in one week. And after fasting the rats for 16 hours, the rats were divided into 3 groups, and when the test solutions (Y) and (Z) shown below were orally administered, before administration, 90 minutes after administration, 180 minutes later, Blood was collected from the tail vein at each timing after 270 minutes and 360 minutes, and serum was obtained according to a conventional method.
(10-2)評価群の構成
(y)GC群: 試験溶液(Y):体重の1kgあたり、GC:1613mg(グルコシルセラミドとして100mg、ニップンセラミドRPS、日本製粉より入手)の用量を投与した。
(z)GC+YG群: 試験溶液(Z):体重の1kgあたり、ヨーグルト(明治ブルガリアヨーグルト脂肪ゼロ、株式会社明治より入手):11.3g、およびGC:1613mgの用量を投与した。
(10-2) Configuration of Evaluation Group (y) GC Group: Test Solution (Y): A dose of GC: 1613 mg (100 mg as glucosylceramide, obtained from Nipunceramide RPS, Nippon Flour) was administered per kg of body weight.
(Z) GC + YG group: Test solution (Z): A dose of yogurt (Meiji Bulgaria yogurt fat zero, obtained from Meiji Co., Ltd.): 11.3 g and GC: 1613 mg per kg of body weight was administered.
(10―3)評価指標
試験溶液を携行した後に、ラット血清中のセラミド量を評価した。
具体的には、Sugawaraらの報告(J. Lipid Res., 2010, 51, 1761-1769)により、グルコシルセラミド投与後に増加することが知られている血清セラミド分子種(d18:2-C16:0、d18:2-C23:0)を指標とした。
(10-3) Evaluation index After carrying the test solution, the amount of ceramide in the rat serum was evaluated.
Specifically, a serum ceramide molecular species (d18: 2-C16: 0) known to increase after glucosylceramide administration according to a report by Sugawara et al. (J. Lipid Res., 2010, 51, 1761-1769). , D18: 2-C23: 0) was used as an index.
[結果]
結果は、図13に示されるとおりであった。
[result]
The result was as shown in FIG.
図13では、血清中のセラミド分子種量の時間曲線下面積を示した。いずれのセラミド分子種も、時間曲線下面積がGC群に比べて、GC+YG群において、有意に高値であった。 FIG. 13 shows the area under the time curve of the amount of ceramide molecular species in serum. All ceramide molecular species were significantly higher in the GC + YG group in terms of the area under the time curve than in the GC group.
グルコシルセラミドとヨーグルトを同時に経口摂取することにより、グルコシルセラミドの吸収が促進されることがわかった。
It was found that the simultaneous absorption of glucosylceramide and yogurt promotes absorption of glucosylceramide.
Claims (19)
The absorption promotion method according to claim 18, wherein the sphingolipid is sphingomyelin.
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| SG11201704736QA SG11201704736QA (en) | 2015-01-06 | 2016-01-05 | Absorption promoter of sphingolipid |
| JP2016568379A JP6773562B2 (en) | 2015-01-06 | 2016-01-05 | Sphingolipid absorption promoter |
| CN201680004953.2A CN107106618B (en) | 2015-01-06 | 2016-01-05 | Sphingolipid absorption enhancer |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2017164298A1 (en) * | 2016-03-24 | 2017-09-28 | 株式会社 明治 | Composition for inhibiting erythema, method of using same, method for preparing same, method for inhibiting erythema, and lactic acid bacteria product |
| WO2018169027A1 (en) * | 2017-03-16 | 2018-09-20 | 株式会社明治 | Phytochemical absorption promoter |
| JP2019099528A (en) * | 2017-12-06 | 2019-06-24 | 株式会社ユーグレナ | Method for producing sphingolipid, composition, moisturizing agent, anti-inflammatory agent and skin barrier function improving agent |
| JPWO2020032100A1 (en) * | 2018-08-08 | 2021-08-10 | 株式会社明治 | Composition for promoting absorption of phytochemicals |
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| JP2001505201A (en) * | 1996-11-22 | 2001-04-17 | デ・シモーネ,クラウディオ | Sphingomyelinase compositions and uses thereof |
| JP2012040015A (en) * | 1999-06-09 | 2012-03-01 | Actial Farmaceutica Soc Por Quotas De Responsabilidade Ltda | Composition containing alkaline sphingomyelinase for use as dietetic preparation, food supplement or pharmaceutical product |
| JP2013181024A (en) * | 2012-03-05 | 2013-09-12 | Snow Brand Milk Products Co Ltd | Fatty acid composition improver |
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| WO2008078387A1 (en) * | 2006-12-26 | 2008-07-03 | Meiji Dairies Corporation | Fermented milk for improving and/or treating skin and method for producing the same |
| CN101301316B (en) * | 2008-06-26 | 2011-06-15 | 福建杨振华851生物科技股份有限公司 | Compound formulation containing lactobacillus leavening and preparation and use thereof |
| JP5876214B2 (en) * | 2010-07-15 | 2016-03-02 | 康友 荒島 | Method for producing lactic acid bacteria symbiotic culture extract |
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| JP2001505201A (en) * | 1996-11-22 | 2001-04-17 | デ・シモーネ,クラウディオ | Sphingomyelinase compositions and uses thereof |
| JP2012040015A (en) * | 1999-06-09 | 2012-03-01 | Actial Farmaceutica Soc Por Quotas De Responsabilidade Ltda | Composition containing alkaline sphingomyelinase for use as dietetic preparation, food supplement or pharmaceutical product |
| JP2013181024A (en) * | 2012-03-05 | 2013-09-12 | Snow Brand Milk Products Co Ltd | Fatty acid composition improver |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017164298A1 (en) * | 2016-03-24 | 2017-09-28 | 株式会社 明治 | Composition for inhibiting erythema, method of using same, method for preparing same, method for inhibiting erythema, and lactic acid bacteria product |
| WO2018169027A1 (en) * | 2017-03-16 | 2018-09-20 | 株式会社明治 | Phytochemical absorption promoter |
| JPWO2018169027A1 (en) * | 2017-03-16 | 2020-01-16 | 株式会社明治 | Phytochemical absorption enhancer |
| JP7177039B2 (en) | 2017-03-16 | 2022-11-22 | 株式会社明治 | Phytochemical absorption enhancer |
| JP2019099528A (en) * | 2017-12-06 | 2019-06-24 | 株式会社ユーグレナ | Method for producing sphingolipid, composition, moisturizing agent, anti-inflammatory agent and skin barrier function improving agent |
| JP7001450B2 (en) | 2017-12-06 | 2022-01-19 | 株式会社ユーグレナ | Compositions and anti-inflammatory agents |
| JPWO2020032100A1 (en) * | 2018-08-08 | 2021-08-10 | 株式会社明治 | Composition for promoting absorption of phytochemicals |
| JP7385572B2 (en) | 2018-08-08 | 2023-11-22 | 株式会社明治 | Composition for promoting phytochemical absorption |
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| CN107106618A (en) | 2017-08-29 |
| TW201630596A (en) | 2016-09-01 |
| JPWO2016111276A1 (en) | 2017-10-12 |
| SG11201704736QA (en) | 2017-07-28 |
| JP6773562B2 (en) | 2020-10-21 |
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