CN106714808A - Agent for promoting production of ceramide covalently bonded to horny cell - Google Patents
Agent for promoting production of ceramide covalently bonded to horny cell Download PDFInfo
- Publication number
- CN106714808A CN106714808A CN201580053481.5A CN201580053481A CN106714808A CN 106714808 A CN106714808 A CN 106714808A CN 201580053481 A CN201580053481 A CN 201580053481A CN 106714808 A CN106714808 A CN 106714808A
- Authority
- CN
- China
- Prior art keywords
- ceramide
- corneocyte
- covalent bonding
- food
- skin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 229940106189 ceramide Drugs 0.000 title claims abstract description 129
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 title claims abstract description 125
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 title claims abstract description 125
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 title claims abstract description 125
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 title claims abstract description 124
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- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013547 stew Nutrition 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 210000000498 stratum granulosum Anatomy 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 210000003684 theca cell Anatomy 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 230000005068 transpiration Effects 0.000 description 1
- 125000002469 tricosyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/688—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols both hydroxy compounds having nitrogen atoms, e.g. sphingomyelins
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Dairy Products (AREA)
Abstract
The present invention relates to an agent for promoting the production of ceramide covalently bonded to a horny cell, which contains a sphingolipid as an active ingredient. The present invention provides: a production promoter which can promote the production of ceramide covalently bonded to a horny cell, and which can safely, simply and economically prevent, inhibit or improve the deterioration of a barrier function of skin; a composition; and a food or beverage.
Description
Related application reference
The application is based on the first No. 2014-158811 (applying date of Japanese patent application Japanese Patent Application：August 4 in 2014
Day) advocate its priority, the entire disclosure is introduced herein as reference.
Technical field
The present invention relates to the generation accelerator with the ceramide of corneocyte covalent bonding.More specifically, this hair
The bright generation accelerator being related to the ceramide of corneocyte covalent bonding, it includes the sphingomyelins matter from milk
(sphingophospholipid).They deteriorate useful to prevention, suppression or improvement skin condition.
Background technology
The cuticula of epidermis is by the corneocyte of epidermal keratinocytes (keratinocyte) terminal differentiation and around it
Corneocyte between lipid constitute.The intercellular lipid is made up of ceramide, cholesterol, aliphatic acid etc., by lipid
Layer forms Rotating fields with water molecule layer.Thus playing prevents from invading the screen with moisture transpiration ex vivo from outside foreign matter
Hinder the effect of function.
Epidermal keratinocytes to outside while entered successively with substrate theca cell, squamous cell, granular cell, corneocyte
Row angling, while forming each layer.Then, hornification coating (cornified is constituted to stratum granulosum synthesis from squamous layer upper strata
Envelope, CE) protein.During cuticula is reached, by transglutaminase, by involucrin, lorica
The cell membrane of the substrate protein such as albumen, cystatin white matter and epidermal keratinocytes combines to form thawless
CE.The thawless CE of the covalent bonds such as ceramide, forms the mating type ceramide (nerve with corneocyte covalent bonding
Acid amides).It is consequently formed the basis of stratum corneum barrier function.
There is cuticula ceramide aliphatic acid the structure of amido link is formed with the sphingosine of long-chain, according to the sphingol
The species of alkali and aliphatic acid, can at least be categorized into 12 kinds (J Lipid Res 2008 1466-1476 pages of volume 49).With cutin
The ceramide of confluent monolayer cells covalent bonding be in these cuticula ceramides ω hydroxyls ceramide and CE covalent bondings that
A little ceramides, refer to the Rotating fields formed by lipid layer and water molecule layer in cuticula ceramide in, especially with
The ceramide of corneocyte film combination.
For the barrier function of skin, it is known that the amount of the ceramide of cuticula is participated in as key factor.Thus, for example
Disclosed in Japanese Unexamined Patent Publication 9-208419 publications with coarse skin-improving benefits, cutin improvement, beautification skin effect
For the purpose of, using the composition for external application comprising mevalonic acid and ceramide type, have studied in the prior art by skin
Skin directly smears ceramide and ceramide is supplied into cuticula.
Although however, the amount of the ceramide of cuticula is normal, observing the skin under ultraviolet irradiation
The low phenomenon of barrier function (such as embodiments herein).The present inventors think, in order to keep the barrier function of skin,
Not only the amount of whole ceramides of cuticula is important, and is also weight with the amount of the ceramide of corneocyte covalent bonding
Want.From from the viewpoint of the formation maturation for promoting hornification coating, such as disclosed in Japanese Unexamined Patent Publication 2008-303185 publications
Specific pyrrolidinone derivatives are used, but according to known to the present inventors, by improving and corneocyte covalent bonding
Ceramide and improve the research of the barrier function of skin and be in progress without what.Then, according to known to the present inventors, wherein at present
Untill do not know sheath lipid orally ingestible still for this purpose.
Disclosed in Japanese Unexamined Patent Publication 2005-281257 publications with sphingomyelins (sphingomyelin) as active ingredient
Beautification skin agent, is disclosed and moisturizing skin is obtained by orally ingestible sphingomyelins, is beautified skin, is prevented that skin is coarse, prevents
The cosmetic results such as wrinkle.In addition, being also disclosed with comprising sphingomyelins in International Publication publication WO2008/093657A pamphlets
The Phospholipids from milk for active ingredient beautification skin agent.
However, in these documents, the sheath lipid on being derived from milk by orally ingestible is covalent with corneocyte to promote
The generation of the ceramide of bonding and can to improve skin barrier function by it low, both without recording or without enlightenment.
Summary of the invention
The present inventors' this is had surprisingly been found that and can be promoted and cutin by orally ingestible sheath lipid, particularly sphingomyelins
The generation of the ceramide of confluent monolayer cells covalent bonding.Then, thus it has also been found that the state of cutaneous malignancies can be improved, enable in particular to
The skin barrier function suppressed under ultraviolet irradiation is low.The present invention is based on these opinions.
Therefore, it is an object of the present invention to provide promoting and the generation of the ceramide of corneocyte covalent bonding
Produce accelerator.In addition, the purpose of the present invention lies also in, there is provided for safety and simplicity, economically prevent, suppress or improve by
The low composition of skin barrier function and diet product caused by ultraviolet irradiation is inferior.
That is, according to the present invention, there is provided invent below.
The generation accelerator of the ceramide of the ＞ of ＜ 1 and corneocyte covalent bonding, it is with sheath lipid as active ingredient.
Generation accelerator of the ＞ of ＜ 2 according to the ＞ of foregoing ＜ 1, sheath lipid is preferably the sphingomyelins matter from milk.
Generation accelerator of the ＞ of ＜ 3 according to the ＞ of foregoing ＜ 1 or the ＞ of ＜ 2, sphingomyelins matter is preferably sphingomyelins.
Generation accelerator of the ＞ of ＜ 4 according to any one of the foregoing ＞ of 1 ＞ of ＜~＜ 3, with corneocyte covalent bond
The ceramide of conjunction is preferably included selected from ω hydroxyls d18:1-C28:0、d18:1-C30:1、d18:1-C30:0、d18:1-C32:0、
d18:1-C32:1、d18:1-C34:0、d18:1-C34:1、d18:1-C36:1、d17:1-C32:0、d17:1-C32:1、d17:
1-C34:0、d17:1-C34:1 and d17:1-C36:One or more of 1 molecular species.
Generation accelerator of the ＞ of ＜ 5 according to any one of the foregoing ＞ of 1 ＞ of ＜~＜ 4, preferably orally ingestible are used or intestines
Grant use in road.
Prevention, suppression or improvement composition that the ＞ skin conditions of ＜ 6 deteriorate, it appoints in including the foregoing ＞ of 1 ＞ of ＜~＜ 5
Active ingredient described in one.
Compositions of the ＞ of ＜ 7 according to the ＞ of foregoing ＜ 6, it is low that the deterioration of skin condition is preferably skin barrier function.
Compositions of the ＞ of ＜ 8 according to the ＞ of foregoing ＜ 7, skin barrier function lowly preferably due in cuticula with angle
Caused by the generation of the ceramide of matter confluent monolayer cells covalent bonding is low.
Compositions of the ＞ of ＜ 9 according to the ＞ of foregoing ＜ 7 or the ＞ of ＜ 8, skin barrier function is lowly preferably shone by ultraviolet
Caused by penetrating.
Compositions of the ＞ of ＜ 10 according to any one of the foregoing ＞ of 6 ＞ of ＜~＜ 9, preferably comprising daily 0.5~1500mg
Can intake sheath lipid.
The ＞ diet products of ＜ 11, its include any one of the foregoing ＞ of 1 ＞ of ＜~＜ 5 with corneocyte covalent bonding
Ceramide generation accelerator.
The ＞ diet products of ＜ 12, its include the prevention that skin condition any one of the foregoing ＞ of 6 ＞ of ＜~＜ 9 deteriorates,
Suppress or improvement composition.
Diet products of the ＞ of ＜ 13 according to the ＞ of foregoing ＜ 11 or the ＞ of ＜ 12, preferably comprising each packaged form 0.2~
45000mg can intake sheath lipid.
Diet products of the ＞ of ＜ 14 according to any one of the foregoing ＞ of 11 ＞ of ＜~＜ 13, it is functional food, health
Nutraceutical, accesary foods, display functionality food, specific health food or display have the food for reducing disease risks.
The ＞ Yoghourts of ＜ 15, its include any one of the foregoing ＞ of 1 ＞ of ＜~＜ 5 with corneocyte covalent bonding
The generation accelerator of ceramide.
The ＞ of ＜ 16 have the Yoghourt for promoting to produce with the ceramide of corneocyte covalent bonding, and it includes additional sheath
Lipid.
Yoghourts of the ＞ of ＜ 17 according to the ＞ of foregoing ＜ 15 or the ＞ of ＜ 16, preferably further comprising collagen.
Yoghourts of the ＞ of ＜ 18 according to any one of the foregoing ＞ of 15 ＞ of ＜~＜ 17, sphingomyelins matter is preferably sphingomyelins.
Diet products of the ＜ 15B ＞ according to any one of the foregoing ＞ of 11 ＞ of ＜~＜ 14, preferred diet product are Yoghourts.
Diet products of the ＜ 16B ＞ according to any one of ＞ the and ＜ 15B ＞ of foregoing 11 ＞ of ＜~＜ 14, preferably further
Comprising collagen.
Diet products of the ＜ 17B ＞ according to any one of foregoing 11 ＞ of ＜~＜ 14 ＞, ＜ 15B ＞ and ＜ 16B ＞, it is excellent
It is sphingomyelins to select sphingomyelins matter.
The ＞ orally ingestibles of ＜ 19 are used or enteron aisle is granted and uses composition, and it is included any one of the foregoing ＞ of 1 ＞ of ＜~＜ 5
With the generation accelerator of the ceramide of corneocyte covalent bonding and Yoghourt.
The ＞ orally ingestibles of ＜ 20 are used or enteron aisle is granted and uses composition, and it includes additional sheath lipid and Yoghourt.
Orally ingestibles of the ＞ of ＜ 21 according to the ＞ of foregoing ＜ 19 or the ＞ of ＜ 20 is used or enteron aisle is granted and uses composition, preferably enters
One step includes collagen.
Orally ingestibles of the ＞ of ＜ 22 according to any one of the foregoing ＞ of 19 ＞ of ＜~＜ 21 is used or enteron aisle is granted and uses group
Compound, preferably sphingomyelins matter are sphingomyelins.
Orally ingestibles of the ＞ of ＜ 23 according to any one of the foregoing ＞ of 19 ＞ of ＜~＜ 22 is used or enteron aisle is granted with combination
Thing, is preferably used for promoting the generation with the ceramide of corneocyte covalent bonding.
The ＞ sheath lipids of ＜ 24, it is used to promote to be produced with the ceramide of corneocyte covalent bonding.
The ＞ of ＜ 25 promote the method produced with the ceramide of corneocyte covalent bonding, including pair and corneocyte
The low object of generation of the ceramide of covalent bonding, orally ingestible or enteron aisle grant sheath lipid.
The ＞ of ＜ 26 prevention, suppress or improve skin condition deteriorate method, including pair with corneocyte covalent bonding
Ceramide produces low object, and orally ingestible or enteron aisle grant sheath lipid.
The purposes of the ＞ sheath lipids of ＜ 27, for promoting to be produced with the ceramide of corneocyte covalent bonding.Preferably,
The purposes is the purposes of sheath lipid, promotes orally to be taken the photograph with what the ceramide of corneocyte covalent bonding was produced for manufacturing
Take or enteron aisle is granted and uses composition.In addition, purposes herein can be the purposes of non-treatment.
The purposes of the ＞ sheath lipids of ＜ 28, the prevention deteriorated for skin condition, suppression or improvement.Preferably, the purposes
It is the purposes of sheath lipid, for manufacturing, the orally ingestible of prevention, suppression or improvement of skin condition deterioration is used or enteron aisle is granted
Use composition.In addition, purposes herein can be the purposes of non-treatment.
The effect of invention
Can promote to be produced with the ceramide of corneocyte covalent bonding using generation accelerator of the invention, especially
It is that can promote thin with cuticula in the epidermis of the state low with the generation of the ceramide of corneocyte covalent bonding
The ceramide of born of the same parents' covalent bonding is produced.Can be effective with the generation of the ceramide of corneocyte covalent bonding by promotion
Ground prevention, suppression improve skin condition deterioration.Particularly it is of the invention generation accelerator and composition can effectively prevent,
Suppress or improve barrier function of the skin under ultraviolet irradiation low.Also, generation accelerator of the invention and composition are
By oral administration or enteral routes intake, further, since raw material be using the thing with the use experience as existing food for originate
, therefore safety and simplicity, it is also excellent in economy.
Brief description
Fig. 1：It is that the figure for showing the passage for testing 1 mesocuticle amount of moisture (has conspicuousness poor between different alphanumerics
Different (p ＜ 0.05)).
Fig. 2：It is to show that the figure for testing the passage of percutaneous moisture evapotranspiration in 1 (has conspicuousness between different alphanumerics
Difference (p ＜ 0.05)).
Fig. 3：It is that the figure of the passage for showing 1 mesocuticle ceramide amount of experiment (exists notable between different alphanumerics
Sex differernce (p ＜ 0.05)).
Fig. 4：It is the figure (* has significant difference (p ＜ 0.05)) of the passage for showing 2 mesocuticle amounts of moisture of experiment.
Fig. 5：It is the figure (* has significant difference (p ＜ 0.05)) of the passage for showing percutaneous moisture evapotranspiration in experiment 2.
Fig. 6：It is to show that (* has aobvious with the figure of the passage of the ceramide amount of corneocyte covalent bonding in experiment 2
Write sex differernce (p ＜ 0.05)).
Fig. 7：It is the figure (there was no significant difference) of the passage for showing 2 mesocuticle ceramide amounts of experiment.
Fig. 8：It is that (* has aobvious for the figure of the passage (each molecular species) for showing the cuticula ceramide amount in experiment 3
Write sex differernce (p ＜ 0.05)).
Fig. 9:It is the figure of the passage (aggregate value of the every value of molecular species) of the cuticula ceramide amount in experiment 3 that shows
Table (* has significant difference (p ＜ 0.05)).
The mode for carrying out an invention
Below, illustrated for embodiments of the present invention.
With the generation accelerator of the ceramide of corneocyte covalent bonding
As described above, the generation accelerator of the ceramide with corneocyte covalent bonding of the invention is with sheath
Lipid is active ingredient.
In this manual, with the ceramide of corneocyte covalent bonding it is ω hydroxyls god in cuticula ceramide
Refer to by lipid layer and hydrone in cuticula through acid amides and those ceramides of hornification coating (CE) covalent bonding
In the ceramide of the Rotating fields that layer is formed, the ceramide with corneocyte film combination.With corneocyte covalent bonding
Ceramide be otherwise referred to as mating type ceramide.
According to currently preferred mode, included with the ceramide of corneocyte covalent bonding and be selected from ω hydroxyls d18:
1-C28:0、d18:1-C30:1、d18:1-C30:0、d18:1-C32:0、d18:1-C32:1、d18:1-C34:0、d18:1-
C34:1、d18:1-C36:1、d17:1-C32:0、d17:1-C32:1、d17:1-C34:0、d17:1-C34:1 and d17:1-C36:
One or more of 1 molecular species.The ceramide with corneocyte covalent bonding is more preferably included and is selected from described group
In more than 3 kinds molecular species, still more preferably comprising selected from more than 5 kinds molecular species in described group.
Sheath lipid
The sheath lipid that can be used in the present invention is derived from natural, for example, can enumerate from milk, Goat Milk, sheep
The sheath lipid of the milk such as milk, mare's milk, from yolk, from rice, from corn, cereal, from konjaku, the sphingolipid from beet etc.
Matter, preferably originates from milk, the sheath lipid more preferably from milk.Sphingolipid is of fine quality to elect sphingomyelins matter, more preferably sphingomyelins as
(sphingomyelin).They can also be prepared by natural material by customary way, it is also possible to use commercially available product.
The sphingomyelins from milk that can be used in the present invention is preferably comprised selected from myristyl sphingosylphosphocholine
(d18:1-C14:0), tricosyl sphingosylphosphocholine (d18:1-C23:0), cetyl sphingosylphosphocholine
(d18:1-C16:0), tricosene base sphingosylphosphocholine (d18:1-C23:1), octadecyl sphingosylphosphocholine
(d18:1-C18:0), tetracosyl sphingosylphosphocholine (d18:1-C24:0), eicosyl sphingosylphosphocholine
(d18:1-C20:0), two tetradecene base sphingosylphosphocholine (d18:1-C24:1), docosyl sphingosylphosphocholine
(d18:1-C22:0) with cerul sphingosylphosphocholine (d18:1-C26:One or more of 0) molecular species.It is described
Sphingomyelins from milk is more preferably included selected from more than three kinds molecular species in described group, still more preferably comprising selected from institute
State more than five kinds molecular species in group.
Preferred mode of the invention, the sphingomyelins from milk is comprised at least and is selected from tricosyl sphingol phosphorus
Sour choline (d18:1-C23:0), cetyl sphingosylphosphocholine (d18:1-C16:0), tetracosyl sphingol phosphoric acid
Choline (d18:1-C24:0), eicosyl sphingosylphosphocholine (d18:1-C20:0) with docosyl sphingol phosphoric acid courage
Alkali (d18:1-C22:One or more of 0) molecular species.The further preferably described sphingomyelins from milk is comprising selected from described
Two or more molecular species in group, it is especially excellent still more preferably comprising selected from more than three kinds molecular species in described group
Choosing comprises at least all five kinds of molecular species in described group.Further preferred mode of the invention, the sheath from milk
Phosphatide comprises at least cetyl sphingosylphosphocholine (d18:1-C16:And/or docosyl sphingosylphosphocholine 0)
(d18:1-C22:0) molecular species.
According to currently preferred mode, generation accelerator of the invention is orally ingestible (i.e. orally ingestible agent) or intestines
Grant use in road (i.e. enteron aisle grants agent).
Generation accelerator of the invention is preferred for the low skin of the skin of state deteriorating, barrier function or and angle
The low skin of generation of the ceramide of matter confluent monolayer cells covalent bonding.
Shown in embodiment as be described hereinafter, according to the present invention, the ceramide amount of cuticula is constant or ceramide amount
Under the increased low state of skin barrier function, can promote to be produced with the ceramide of corneocyte covalent bonding, keep
Or improve skin barrier function.Therefore, it is of the invention to produce accelerator to be more preferably used for the ceramide amount of cuticula not
Become or the low skin of the skin of the increased state deteriorating of ceramide amount, barrier function or with corneocyte covalent bonding
The low skin of generation of ceramide.
Can as described later using the generation accelerator of the ceramide with corneocyte covalent bonding of the invention
Expect to keep or increase cuticlar water component, keep or reduce percutaneous moisture evapotranspiration, therefore, the present invention is also provided with sheath lipid
It is the retention agent or dose of the cuticlar water component of active ingredient, percutaneous moisture evapotranspiration with sheath lipid as active ingredient
Retention agent reduces agent.
Purposes
There is the ceramide promoted with corneocyte covalent bonding as the sheath lipid of the active ingredient in the present invention
The activity (embodiment described later) of generation, prevention, suppression or the improvement for deteriorating with skin condition in addition.
Here, promoting to include and corneocyte covalent bonding with the generation of the ceramide of corneocyte covalent bonding
The ceramide promotion for producing, the maintenance that produces, gentrify produce low state.
Here, so-called skin condition deteriorates referring to, such as barrier function comprising skin is low, dry skin, skin are thick
Rough, cuticula amount of moisture reduction, atopic dermatitis etc..Skin barrier function is lowly also comprising maintenance barrier function.In addition, skin
It is low that skin barrier function is lowly preferably barrier function of the skin under ultraviolet irradiation.
In addition, here, " prevention, suppress or improve " of degradation mode be postponed with the regulation comprising this state, development,
Relax, morbidity prevention, again send out prevention etc. the meaning use.
Another way of the invention, attempts by promoting to be produced with the ceramide of corneocyte covalent bonding,
Can realize treating, prevent or improving the state that can be treated, prevent or improve.
Composition and diet product
As described above, according to the present invention, there is provided prevention, suppression or improvement composition that skin condition deteriorates, its
Comprising active ingredient of the invention, i.e. sheath lipid.Said composition also can be comprising of the invention and corneocyte covalent bonding
Ceramide generation accelerator.In addition, according to the present invention, there is provided diet product, it includes of the invention thin with cuticula
The generation accelerator of the ceramide of born of the same parents' covalent bonding.
Such composition and diet product can for example be manufactured by manufacture method, methods described be included in composition and
Generation accelerator of the invention is added in the material composition of diet product.
Used as a preferred mode, prevention, suppression or the improvement composition that skin condition of the invention deteriorates are medicines
Compositions.
In the present invention, pharmaceutical composition refer to and use may be allowed to for formulation additive, according to well-established law with oral
Preparation or non-oral formulation form and prepare.Tablet, powder, granula subtilis, particle can be taken in the case of oral formulations
The mode of the liquid preparation such as the solid pharmaceutical preparations such as agent, capsule, pill, sustained release agent, solution, suspension, emulsion.In addition, non-
The mode of injection, suppository can be taken in the case of oral formulations.From from the viewpoint of simplification, preferably oral formulations.
As may be allowed to for formulation additive, can for example enumerate excipient, stabilizer, preservative, wetting agent, emulsifying agent,
Lubricant, sweetener, colouring agent, spices, buffer, antioxidant, pH adjusting agent etc..
Any condition can be as needed added in diet product of the invention.As it is such can arbitrarily add into
Point, it is not particularly limited, composition, sweetener, acid, veterinary antibiotics, seed fruit in diet product usually can be coordinated
Juice or useful micro- such as nutrient, lactic acid bacteria, Bifidobacterium, the bacterium acidi propionici such as its extract, vitamin, mineral matter, amino acid
Biological or its culture, oligosaccharides etc. have functional carbohydrate, royal jelly, collagen, ceramide, Glucosamine, astaxanthin,
The existing functional material such as polyphenol, spices, pH adjusting agent, excipient, acid, colouring agent, emulsifying agent, preservative agent etc..
In a preferred embodiment of the invention, using collagen as be added in diet product (preferably Yoghourt) it is any into
Point.
In the present invention, so-called diet product refers to the material in addition to pharmaceutical composition, can be solution, suspension, breast
The mode of the orally available intakes such as turbid liquid, powder, shaped solid thing, is not particularly limited.Specifically, newborn drink can for example be enumerated
The dairy produce such as material, Yoghourt class, sour milk beverage, acidified milk, ice cream, milk oils, cheese class；Cold drink, fruit drink,
The powder drinks such as vegetable beverage, soyabean milk beverage, coffee beverage, tea beverage, fruit syrup, cocoa, Sorbet, motion powder drink,
The drink such as the powder drink of fortification, powdered food product cosmetically, powder soup, material, beverage concentrate, the alcoholic beverage of steaming dessert
Material class；The wheat powder products such as bread, pasta, noodles, cake premixed powder, fried flour, bread flour；Chocolate, chewing gum,
The snack categories such as the dessert dessert such as sugar, biscuit, soft sweets, snacks, Japanese dessert, jelly, pudding；Processing and seasoning material, flavoring,
The flavorings such as premix culinary art material；Curry, pasta sauce, thick soup, stew, the soft canned food of Japanese flavor food；Processing
The grease types such as grease, butter, margarine, daub sauce, mayonnaise；The fast food class such as frozen dried food；Agricultural production can, fruit
The agricultural production processed goods such as sauce marmalade orange class, pickles, cooked beans, cereal product, dish congee；Fishery technology；Livestock products；Pizza,
Fish shellfish chicken rice, milk dry junket and iron the frozen food such as dish, home cooking, Orly；Spoon meat and animal feed, small pieces, mouth
Cosmetics used in chamber etc..
A preferred embodiment of the invention, diet product is milk beverage (can be comprising processing milk), acidified milk, refrigerant drink
Material, fruit syrup, small pieces, the formula milk of cosmetically powdered food product, powder drink, spoon meat, liquid, according to preferred
Mode, diet product is milk beverage, acidified milk, cold drink, fruit syrup, small pieces, powdered food product cosmetically, according to further
Preferred mode, diet product is milk beverage (can be comprising processing milk), acidified milk (Yoghourt).
In addition, diet product also includes functional food, health-nutrition food, accesary foods, healthy food, display functionality
Food, specific health food, trophic function food, patient with food, baby formula milk powder, pregnant and lying-in women or nursing period woman
Lady's milk powder or display have the food of the diet product so classification for reducing disease risks.One of the invention preferred side
Formula, diet product be functional food, health-nutrition food, accesary foods, the food of display functionality, specific health food or
Display has the food for reducing disease risks.
Additionally, here, display reduce disease risks be show with reduce disease risks possibility diet product, can
Based on the FAO/WHO combination food specifications committee (Codex Committee on Food) formulate specification or with its specification be with reference to determine
Display or the display of accreditation.
Therefore, diet product of the invention can for example be suitable for expecting to improve or relax the consumption that skin condition deteriorates
The food of person, the form offer for being suitable to improve food, i.e. so-called specific health food that skin condition deteriorates.
Another way of the invention, there is provided show by the product with the ceramide of corneocyte covalent bonding
The raw prevention for promoting to bring, the diet product for suppressing or improving the function that skin condition deteriorates.
Content of the active ingredient in diet product and composition can improve according to the species of composition, mode, prevention
Purpose etc. and change, accordingly, it is difficult to specify without exception, can be adjusted to be grown up (body weight 60kg) for composition of the invention
Daily 0.5~1500mg, preferably 1~1000mg, more preferably 5~500mg sheaths lipid (preferably originate from the sheath lipid of milk, more preferably
Sphingomyelins from milk) it is ingestible effective dose.
The assay method of sheath lipid can be carried out by customary way, and AQUASIL is used for example with liquid chromatography
SP100 (4.6X250mm, セ Application シ ュ ー science society) is determined as post.
Now, as mobile phase, such as preferably using making 0.5mM phosphoric acid-citrate buffer solution (pH3.0) and methyl alcohol with 5 ratios
The solution that 95 ratio is obtained by mixing.Can by minute be set as 20 minutes, the flow velocity of mobile phase be 0.6mL/ minutes, post
Temperature is 40 DEG C, is detected with absorbance 205nm.As standard substance, for example, (milk, the good サ イ エ of length can be derived from using sphingomyelins
Application ス societies manufacture), can be quantified by area ratio.
In another way of the invention, content of the active ingredient in diet product and composition can also be packed with each
Mode specifies, such as in the case of diet product, the content of sheath lipid be with 5~1500mg, preferably 6~1000mg, more preferably 7~
500mg includes sheath lipid, in addition, in the case of composition, the content of sheath lipid be can with 0.5~1500mg, preferably 1~
1000mg, more preferably 5~500mg include sheath lipid.In addition, the amount of each manner of packing is not limited to intake once,
In the case of being the amount of the intake for including multiple part or many gifts (such as 30 gifts), such as diet product, sheath lipid
Content is can to include sheath lipid with 5~45000mg, preferably 6~30000mg, more preferably 7~15000mg, in addition, composition
In the case of, the content of sheath lipid is can be included with 0.5~45000mg, preferably 1~30000mg, more preferably 5~15000mg
Sheath lipid.
In existing common milk beverage, acidified milk, Phospholipids 20mg is included per 1g lipids, and milk beverage of the invention, hair
In kefir milk, 25~3000mg of Phospholipids, more preferably preferably 30~2500mg, 40~2000mg can be included per 1g lipids, enter one
Step preferably 50~1500mg.In addition, in existing common milk beverage, acidified milk, sphingomyelins 6mg is included per 1g lipids, and this hair
In bright milk beverage, acidified milk, per 1g lipids can comprising 7~1500mg of sphingomyelins, preferably 8~1250mg, more preferably 9~
1000mg, further preferred 10~750mg.That is, in a preferred embodiment of the invention, using intentionally improve Phospholipids
The milk beverage or acidified milk of the content (preferably sphingomyelin content) of (particularly sheath lipid).
Therefore, a preferred embodiment of the invention, there is provided with the god promoted with corneocyte covalent bonding
Through the Yoghourt that acid amides is produced, it includes additional sheath lipid." additional sheath lipid " said here is the sphingolipid that it is possible to additionally incorporate
Matter, is not sheath lipid that Yoghourt was included originally, and refers to that sheath lipid is it is possible to additionally incorporate in Yoghourt, and sheath is intentionally improve making
Added during the Yoghourt of lipid concentration.
In milk beverage of the invention, acidified milk, with situation of the amount commonly comprising lipid (such as including lipid with 3 weight %)
Under can include 1~300mg/g of Phospholipids, more preferably preferably 1.5~250mg/g, 2~200mg/g, further preferred 2.5~
150mg/g.In addition, in milk beverage of the invention, acidified milk, sphingomyelins can be included in the case of including lipid with amount commonly
0.2~60mg/g, preferably 0.25~50mg/g, more preferably 0.3~40mg/g, further preferred 0.35~30mg/g.
On the other hand, in milk beverage of the invention, acidified milk, (lipid is for example being included with 1 weight % comprising lipid on a small quantity
It is low-fat) in the case of can comprising 0.5~300mg/g of Phospholipids, preferably 0.6~250mg/g, more preferably 0.7~
200mg/g, further preferred 0.8~150mg/g.In addition, in milk beverage of the invention, acidified milk, lipid is being included on a small quantity
In the case of, 0.05~60mg/g of sphingomyelins, more preferably preferably 0.1~50mg/g, 0.15~40mg/g can be included, it is further excellent
Select 0.2~30mg/g.
Then, in milk beverage of the invention, acidified milk, cold drink, fruit syrup, small pieces, powdered food product cosmetically,
0.2~300mg/g of Phospholipids, preferably 0.3~250mg/g can be included in the case where lipid (fat-free) is practically free of,
More preferably 0.4~200mg/g, further preferred 0.5~150mg/g.In addition, in milk beverage of the invention, acidified milk, almost
0.02~60mg/g of sphingomyelins, more preferably preferably 0.04~50mg/g, 0.06~40mg/ can be included in the case of without lipid
G, further preferred 0.08~30mg/g.
Another correspondence of the invention, there is provided the generation promotion side with the ceramide of corneocyte covalent bonding
Method, including grant sphingolipid to the oral intake low with the generation of the ceramide of corneocyte covalent bonding or enteron aisle
Matter.
Additionally, here, it is preferred that methods described is the method in addition to medical application.In addition, as the object, preferably
People or the mammality in addition to people.
Then, methods described can be preferably used to pair to be reduced with the generation of the ceramide of corneocyte covalent bonding
Object, to make within more than 2 days, sheath lipid continues orally ingestible or enteron aisle is granted, and promotes the nerve with corneocyte covalent bonding
The method that acid amides is produced.
Embodiment
Below, it is described in detail by following embodiments for the present invention, but the present invention is not limited to this.
The sheath lipid for using
As sheath lipid, use with Phospholipids concentrate (PC700, Off of the 16.0 weight % comprising the sphingomyelins from milk
ォ Application テ ラ societies).
The composition of the sphingomyelin molecular species of actually used Phospholipids concentrate is shown in table 1 below.
Additionally, carrying out the measure of sphingomyelin molecular species composition in the following manner.
The measure of sphingomyelin molecular species composition
Phospholipids concentrate is dissolved in the Tris buffer solutions (pH7.4) for adding 2%Triton X-100.Add 1U
Sphingomyelinase (シ グ マ societies), makes its reaction 2 hours, by sphingomyelin hydrolysis into ceramide at 37 DEG C.Use chloroform methanol
Mixed liquor (2:1, v/v) the ceramide molecular species for having hydrolyzed is extracted.
For the ceramide molecular species for extracting, using liquid chromatography quality analysis apparatus LC/MS/MS (Quatro
Premier XE (Waters societies)), use ACQUITY UPLC BEH C18 (2mm × 100mm, 1.7 μm of particle diameter, Waters societies)
It is measured as post.
Now, using ammonium acetate (5mM)/acetonitrile as mobile phase A, ammonium acetate (5mM)/methyl alcohol (95%) is used as mobile phase
B.Then, the mobile phase A since 100%, Mobile phase B becomes 100% after gradient is entered to exercise 30 minutes, is 100% by Mobile phase B
Kept for 2 minutes, and then after 3 minutes, be replaced with mobile phase A and become 100%.Namely by a survey for sample of LC/MS/MS
Fix time and be set to 35 minutes.Additionally, by the flow rate set of mobile phase be 0.4mL/ minute, column temperature be 40 DEG C, with cation
Pattern is detected using electro-spray ionization.As the situational variables of LC/MS/MS, the voltage of capillary is set as
3000V, the temperature in source are 120 DEG C, the temperature of desolventizing is 400 DEG C, the flow velocity of desolvation gas is 850L/h, the stream of taper hole gas
Speed is 50L/h, taper hole voltage is 30eV/h.
The amount of sphingomyelin molecular species is calculated by the molar concentration of the ceramide molecular species for obtaining.
[table 1]
Table 1：The composition of sphingomyelin molecular species
| Molecular species | Content [mg/g] | Molecular species | Content [mg/g] |
| d18:1-C14:0 | 1.14 | d16:1-C16:0 | 3.62 |
| d18:1-C16:0 | 15.10 | d16:1-C22:0 | 10.07 |
| d18:1-C18:0 | 1.06 | d16:1-C23:0 | 15.85 |
| d18:1-C20:0 | 0.31 | d16:1-C24:0 | 10.15 |
| d18:1-C22:0 | 7.43 | d17:1-C16:0 | 2.60 |
| d18:1-C23:0 | 12.05 | d17:1-C22:0 | 2.01 |
| d18:1-C23:1 | 2.31 | d17:1-C23:0 | 3.04 |
| d18:1-C24:0 | 7.80 | d17:1-C24:0 | 2.06 |
| d18:1-C24:1 | 2.15 | ||
| d18:1-C25:0 | 0.38 | ||
| d18:1-C26:0 | 0.14 |
Experiment 1：The influence of sphingolipid confrontation dry skin (Dry)
Allow hairless mouse to absorb the feed of induction dry skin (Dry), investigate the orally ingestible of Phospholipids concentrate
Influence.
The induction of (1-1) Dry
Make hairless mouse (Hos：HR-1, female, 4 week old) after domestication 1 week, allow it freely to absorb and induce Dry
Feed (special feed HR-AD, the manufacture of Japanese agricultural production industry society) 8 weeks.
The composition of (1-2) evaluation group
Using the test system of Dry animal pattern, evaluate by the orally ingestible band of Phospholipids concentrate (PC700)
The influence to skin condition for coming.Now, the mouse of each group is respectively 10.
The group of zoopery is constituted into (composition of evaluation group) and is shown in table 2 below with the relation of the content of sphingomyelins.
[table 2]
Table 2：The group of zoopery constitutes the relation with the content of sphingomyelins
(1-3) evaluation test method
For each experimental animal group, cuticlar water component, percutaneous moisture evapotranspiration (TEWL) and and corneocyte are determined
The ceramide amount of covalent bonding, thus evaluates the barrier function of skin.
(a) cuticlar water component
Using Corneometer (Corneometer, Courage and Khazaka Electronic GmbH manufactures),
Cuticlar water component is determined with 5 times/.Wherein, using three average out to of measured value after eliminating maximum and minimum value
Cuticlar water component.
(b) percutaneous moisture evapotranspiration (TEWL)
Use Tewemeter (Tewemeter MPA580, Courage and Khazaka Electronic GmbH systems
Make) percutaneous moisture evapotranspiration is determined, it uses 29 DEG C of probe assays of insulation 20 seconds.For the measurement result that these are obtained,
Using the percutaneous moisture evapotranspiration of the average out to of 3 times.
The ceramide amount of (c) and corneocyte covalent bonding
For the ceramide amount with corneocyte covalent bonding, using liquid chromatography quality analysis apparatus LC/MS/
MS (Quatro premier XE (Waters societies)), uses ACQUITY UPLC BEH C18 (2mm × 100mm, the μ of particle diameter 1.7
M, Waters society) it is measured as post.
Now, using ammonium acetate (5mM)/acetonitrile as mobile phase A, ammonium acetate (5mM)/methyl alcohol (95%) is used as mobile phase
B.Then, the mobile phase A since 100%, Mobile phase B becomes 100% after gradient is entered to exercise 30 minutes, is 100% by Mobile phase B
Kept for 2 minutes, and then after 3 minutes, be replaced with mobile phase A and become 100%.Namely by a survey for sample of LC/MS/MS
Fix time and be set to 35 minutes.Additionally, by the flow rate set of mobile phase be 0.4mL/ minute, column temperature be 40 DEG C, with cation
Pattern is detected using electro-spray ionization.As the situational variables of LC/MS/MS, the voltage of capillary is set as
3000V, the temperature in source are 120 DEG C, the temperature of desolventizing is 400 DEG C, the flow velocity of desolvation gas is 850L/h, the stream of taper hole gas
Speed is 50L/h, taper hole voltage is 30eV/h.
(d) cuticula ceramide amount
For cuticula ceramide amount, using liquid chromatography quality analysis apparatus LC/MS/MS (Quatro
Premier XE (Waters societies)), use ACQUITY UPLC BEH C18 (2mm × 100mm, 1.7 μm of particle diameter, Waters societies)
It is measured as post.
Now, using ammonium acetate (5mM)/acetonitrile as mobile phase A, ammonium acetate (5mM)/methyl alcohol (95%) is used as mobile phase
B.Then, the mobile phase A since 100%, Mobile phase B becomes 100% after gradient is entered to exercise 30 minutes, is 100% by Mobile phase B
Kept for 2 minutes, and then after 3 minutes, be replaced with mobile phase A and become 100%.Namely by a survey for sample of LC/MS/MS
Fix time and be set to 35 minutes.Additionally, by the flow rate set of mobile phase be 0.4mL/ minute, column temperature be 40 DEG C, with cation
Pattern is detected using electro-spray ionization.As the situational variables of LC/MS/MS, the voltage of capillary is set as
3000V, the temperature in source are 120 DEG C, the temperature of desolventizing is 400 DEG C, the flow velocity of desolvation gas is 850L/h, the stream of taper hole gas
Speed is 50L/h, taper hole voltage is 30eV/h.
For cuticula ceramide amount, cetyl sphingol (d18 is sought:1-C16:0), octadecyl sphingol
(d18:1-C18:0), eicosyl sphingol (d18:1-C20:0), docosyl sphingol (d18:1-C22:0), 20
Tri-alkylshpingosines (d18:1-C23:0), tricosene base sphingol (d18:1-C23:1), tetracosyl sphingol (d18:
1-C24:0), two tetradecene base sphingol (d18:1-C24:1) with cerul sphingol (d18:1-C26:0) summation.
The standard substance that the standard substance of each ceramide is manufactured using Avanti Polar Lipids societies, is determined by area ratio
Amount.
(1-4) evaluation result
Result is as described below.
(a) cuticlar water component
Result is as shown in Figure 1.
In Fig. 1, compared with the cuticlar water component of normal group, the cuticlar water component of HD-AD groups is low value.The opposing party
Face, compared with the cuticlar water component of HD-AD groups, L-MPL groups are high level with the cuticlar water component of H-MPL groups.Thus, it is possible to
Say in L-MPL groups and H-MPL groups, the deterioration of skin barrier function is suppressed.
(b) percutaneous moisture evapotranspiration (TEWL)
Result is as shown in Figure 2.
In fig. 2, compared with the TEWL of normal group, the TEWL of HD-AD groups is high level.On the other hand, with HD-AD groups
TEWL is compared, and L-MPL groups are low values with the TEWL of H-MPL groups.Thus, it is possible to say in L-MPL groups and H-MPL groups, skin screen
The deterioration for hindering function is suppressed.
The ceramide amount of (c) and corneocyte covalent bonding
Result is as described in Table 3.
[table 3]
Table 3：With the content ratio [weight %] of the ceramide amount of corneocyte covalent bonding
The content ratio with the ceramide of corneocyte covalent bonding is shown in table 3.It is common for corneocyte
The content ratio of the ceramide that valence link is closed, with each and cuticula of the normal group in off-test (after test food is absorbed 8 weeks)
The ceramide amount of cell covalent bonding be 100, with relative value represent other respectively with the neural acyl of corneocyte covalent bonding
Amine amount.
Here, compared with the content ratio of the ceramide with corneocyte covalent bonding of normal group, HD-AD groups it is each
Content ratio with the ceramide of corneocyte covalent bonding is low value.On the other hand, each and cuticula with HD-AD groups is thin
The content ratio of the ceramide of born of the same parents' covalent bonding is compared, the ceramide of each and corneocyte covalent bonding of H-MPL groups
Content ratio is high level.Thus, it is possible to say in L-MPL groups and H-MPL groups, the deterioration of skin barrier function is suppressed.
(d) cuticula ceramide amount
Result is as shown in Figure 3.
From result, compared with the cuticula ceramide amount of normal group, each cuticula ceramide amount of HD-AD groups
It is constant or increase on the contrary.On the other hand, as described above, the ceramide with corneocyte covalent bonding with normal group
Content ratio compare, the content of the ceramide of each and corneocyte covalent bonding of HD-AD groups is than reducing.
Understand, even if skin condition deteriorates, will not also cause the reduction of cuticula ceramide amount, but cuticula is neural
Acid amides amount is normal value or increases on the contrary, on the other hand, can be observed and the ceramide of corneocyte covalent bonding
Amount and the tendency of cuticula ceramide amount independence, deteriorate concomitantly with skin condition, and its amount is reduced.
(e) other
Skin surface to each group mouse is visually observed, and as a result substantially observes that HD-AD groups are caused by Dry
Pachylosis state, and H-MPL groups are the good skin conditions with normal group phase same level.
In addition, carrying out the histological institute that HD dyeing is observed by microscope according to the surface skin member for taking each group
See, H-MPL groups are the good skin conditions with normal group phase same level.
Experiment 2：The influence that barrier function of the sphingolipid confrontation skin under ultraviolet irradiation deteriorates
By to hairless mouse irradiation ultraviolet radiation, making the barrier function of skin low, the oral of Phospholipids concentrate is investigated
Absorb the influence to the state.
(2-1) is irradiated the induction of the low state of caused skin barrier function by ultraviolet
Make hairless mouse (Hos：HR-1, female, 4 week old) domestication 1 week after, in 20mJ/cm2Under conditions of, irradiate ultraviolet
Line (UV-B (GL20SE, the manufacture of three common-battery gas Co., Ltd.)).
The composition of (2-2) evaluation group
Using the test system of Dry animal pattern, evaluate by sphingomyelins (purity：98%, the good サ イ エ Application ス of length
Society manufactures) influence to skin condition that brings of orally ingestible (orally granting).Now, each group mouse is respectively 10.By animal
Group composition (composition of evaluation group) of experiment is shown in following with the relation of sphingomyelin content.
Control group：Absorb the group of usual feed
SM groups：With 146mg/kg/ days by sphingomyelins (purity：98%) the oral group granted
(2-3) evaluation test method
Carried out in the same manner as (1-3) item of experiment 1, for each experimental animal group, determine cuticlar water component, percutaneous moisture
The ceramide amount and cuticula ceramide amount of evapotranspiration (TEWL) and corneocyte covalent bonding, thus evaluate skin
Barrier function.
(2-4) evaluation result
Result is as described below.
(a) cuticlar water component
Result is as shown in Figure 4.
The 2nd day and the 3rd day of experiment, compared with the cuticlar water component of control group, the cuticlar water component of SM groups is high
Value.
(b) percutaneous moisture evapotranspiration (TEWL)
Result is as shown in Figure 5.
Here, the 2nd day and the 3rd day of experiment, compared with the TEWL of control group, the TEWL of SM groups is low value.
The ceramide amount of (c) and corneocyte covalent bonding
Result is as shown in Figure 6.
Here, showing the ceramide amount (d18 with corneocyte covalent bonding：1-C34：1) passage.For with
The ceramide amount of corneocyte covalent bonding, the god with corneocyte covalent bonding during with on-test in control group
It is 100 through acid amides amount, other ceramide amounts with corneocyte covalent bonding is represented with relative value.Here, and control group
Compared with the ceramide amount of corneocyte covalent bonding, the ceramide amount with corneocyte covalent bonding of SM groups
It is high level.
(d) cuticula ceramide amount
Result is as shown in Figure 7.
Even if under understanding to be irradiated by ultraviolet, will not also cause the reduction of cuticula ceramide amount, cuticula nerve acyl
Amine amount is normal value or increased on the contrary, on the other hand, can be observed and the ceramide of corneocyte covalent bonding
Amount and this independent tendency, deteriorate concomitantly with skin condition, and its amount is reduced.
Imply that by orally ingestible sphingomyelins, the skin barrier function based on ultraviolet can be suppressed and deteriorated.And imply
Continue to absorb more than 2 days sphingomyelins journeys, it is easy to suppress the deterioration of skin barrier function.
Experiment 3：The influence of the people of sphingolipid confrontation dry skin
Investigation food of the intake containing Phospholipids concentrate is to the influence for feeling the women for drying symptom.
The preparation of (3-1) test meal
8.8 parts of allotment skimmed milk milk, 5.3 parts of granulated sugar, 1.7 parts of milk proem matter, 1.7 parts of collagen peptide, 0.2 part of producing starch,
0.1 part of polysaccharide of thickening, 0.04 part of Phospholipids concentrate, 0.05 part of spices, 0.01 part of acid, 0.01 part of arginine, sweet taste
82.0 parts of 0.0001 part of agent and water, it is sterilized with the condition of 1 minute at 95 DEG C.Then, protected with 0.15% addition in the raw material milk
Plus Leah lactobacillus (Lactobacillus bulgaricus) and streptococcus thermophilus (Streptococcus
Thermophilus mixing bottle opener), in 37 DEG C~45 DEG C fermentations, is manufactured as the Yoghourt of test meal as Yoghourt bottle opener.
Test meal 75g includes collagen 1000mg (new field ゼ ラ チ Application society) and Phospholipids concentrate (PC700, Off ォ
Application テ ラ societies) (including sphingomyelins 10mg).
(3-2) evaluation test method
Allow with conscious 32 women (forum participant) for drying symptom, absorb the test meal 4 containing sphingomyelins
Week, daily 75g (being 10mg as sphingomyelins).
(3-3) evaluation index
The past wrist inside portion is taken with PPS adhesive tapes (PPS film adhesive tapes, temple ridge makes institute) from same position before and after intake
Add up to 3 pieces of cuticula, evaluate the ceramide amount (d18 with corneocyte covalent bonding:1-C28:0、d18:1-C30:0、
d18:1-C30:1、d18:1-C32:0、d18:1-C32:1、d18:1-C34:0、d18:1-C34:1、d18:1-C36:0、d18:
1-C36:1 and its summation).
(3-4) evaluation result
Result is as described below.
With the ceramide amount of corneocyte covalent bonding
Result is as can be seen from figures 8 and 9.
With the summation of the ceramide amount of corneocyte covalent bonding be high level compared with before intake, after intake.In addition,
It is also for high level after intake compared with before intake in ceramide amount respectively with corneocyte covalent bonding.Thus, show
Show that, by continuing to absorb the food comprising sphingomyelins, the ceramide with corneocyte covalent bonding increases.
Claims (18)
1., with the generation accelerator of the ceramide of corneocyte covalent bonding, it is with sheath lipid as active ingredient.
2. generation accelerator according to claim 1, wherein the sphingolipid matter is the sphingomyelins matter from milk.
3. generation accelerator according to claim 1 and 2, its sphingomyelin matter is sphingomyelins.
4. the generation accelerator according to any one of claims 1 to 3, wherein the nerve with corneocyte covalent bonding
Acid amides is comprising selected from ω hydroxyls d18:1-C28:0、d18:1-C30:1、d18:1-C30:0、d18:1-C32:0、d18:1-C32:
1、d18:1-C34:0、d18:1-C34:1、d18:1-C36:1、d17:1-C32:0、d17:1-C32:1、d17:1-C34:0、
d17:1-C34:1 and d17:1-C36:One or more of 1 molecular species.
5. the generation accelerator according to any one of Claims 1 to 4, it is that orally ingestible is used or enteron aisle grants use.
6. skin condition deteriorates prevention, suppression or improvement composition, it is included any one of Claims 1 to 5
Active ingredient.
7. composition according to claim 6, the wherein deterioration of skin condition are that skin barrier function is low.
8. composition according to claim 7, wherein skin barrier function be lowly by with corneocyte covalent bonding
Generation of the ceramide in cuticula it is low caused by.
9. the composition according to claim 7 or 8, wherein skin barrier function are lowly by caused by ultraviolet irradiation.
10. the composition according to any one of claim 6~9, its include daily 0.5~1500mg can intake sheath
Lipid.
11. diet products, it includes the ceramide with corneocyte covalent bonding any one of Claims 1 to 5
Generation accelerator.
12. diet products, it includes prevention, suppression or the improvement use that the skin condition any one of claim 6~9 deteriorates
Composition.
13. diet product according to claim 11 or 12, it includes each 0.2~45000mg of packaged form can intake
Sheath lipid.
14. diet product according to any one of claim 11~13, it is functional food, health-nutrition food, auxiliary
Helping food, display functionality food, specific health food or display has the food for reducing disease risks.
15. Yoghourts, its include any one of Claims 1 to 5 with the ceramide of corneocyte covalent bonding
Produce accelerator.
16. have the Yoghourt for promoting to produce with the ceramide of corneocyte covalent bonding, and it includes additional sheath lipid.
17. Yoghourt according to claim 15 or 16, it further includes collagen.
18. Yoghourt according to any one of claim 15~17, its sphingomyelin matter is sphingomyelins.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014158811 | 2014-08-04 | ||
| JP2014-158811 | 2014-08-04 | ||
| PCT/JP2015/072030 WO2016021573A1 (en) | 2014-08-04 | 2015-08-04 | Agent for promoting production of ceramide covalently bonded to horny cell |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106714808A true CN106714808A (en) | 2017-05-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580053481.5A Pending CN106714808A (en) | 2014-08-04 | 2015-08-04 | Agent for promoting production of ceramide covalently bonded to horny cell |
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| Country | Link |
|---|---|
| JP (1) | JPWO2016021573A1 (en) |
| CN (1) | CN106714808A (en) |
| SG (2) | SG11201700758SA (en) |
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| WO (1) | WO2016021573A1 (en) |
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| JP7061560B2 (en) * | 2016-03-24 | 2022-04-28 | 株式会社明治 | Fermented milk for promoting absorption of sphingomyelin and suppressing the formation of erythema, its use and its production method, a method for promoting the absorption of sphingomyelin and suppressing the formation of erythema, fermented milk containing lactic acid bacteria product and sphingomyelin. |
| WO2019193037A1 (en) * | 2018-04-03 | 2019-10-10 | N.V. Nutricia | Nutritional composition for use in the prevention of dry skin |
| WO2024100919A1 (en) * | 2022-11-11 | 2024-05-16 | 一丸ファルコス株式会社 | Agent containing sphingoid base for use in prevention of pruritus, and use thereof |
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| JP2011111434A (en) * | 2009-11-30 | 2011-06-09 | Obihiro Univ Of Agriculture & Veterinary Medicine | Skin function-improving agent, and food and drink containing the same |
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2015
- 2015-08-04 SG SG11201700758SA patent/SG11201700758SA/en unknown
- 2015-08-04 CN CN201580053481.5A patent/CN106714808A/en active Pending
- 2015-08-04 WO PCT/JP2015/072030 patent/WO2016021573A1/en active Application Filing
- 2015-08-04 SG SG10201900961PA patent/SG10201900961PA/en unknown
- 2015-08-04 TW TW104125237A patent/TW201618789A/en unknown
- 2015-08-04 JP JP2016540234A patent/JPWO2016021573A1/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1374078A (en) * | 2001-03-06 | 2002-10-16 | 花王株式会社 | Composition for external use |
| CN1694684A (en) * | 2002-11-19 | 2005-11-09 | 金伯利-克拉克环球有限公司 | Products and methods for maintaining or increasing ceramide levels in skin |
| US20070270382A1 (en) * | 2003-10-02 | 2007-11-22 | Changseo Park | Composition for Protecting Skin |
| CN1997376A (en) * | 2004-03-30 | 2007-07-11 | 雪印乳业株式会社 | Skin conditioning agent |
| CN101466352A (en) * | 2006-06-14 | 2009-06-24 | 株式会社夏洛美 | Cosmetic and method of producing the same |
| CN101653561A (en) * | 2008-08-18 | 2010-02-24 | 复旦大学附属中山医院 | Ceramide production accelerant |
| CN103876956A (en) * | 2012-12-20 | 2014-06-25 | 赵翠 | Moisture-retention skin-care composition |
Also Published As
| Publication number | Publication date |
|---|---|
| SG11201700758SA (en) | 2017-02-27 |
| WO2016021573A1 (en) | 2016-02-11 |
| TW201618789A (en) | 2016-06-01 |
| SG10201900961PA (en) | 2019-02-27 |
| JPWO2016021573A1 (en) | 2017-05-25 |
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