CN109731001A - The newly new application of fine jade oligosaccharides and the composition containing new fine jade oligosaccharides - Google Patents

The newly new application of fine jade oligosaccharides and the composition containing new fine jade oligosaccharides Download PDF

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CN109731001A
CN109731001A CN201910112630.0A CN201910112630A CN109731001A CN 109731001 A CN109731001 A CN 109731001A CN 201910112630 A CN201910112630 A CN 201910112630A CN 109731001 A CN109731001 A CN 109731001A
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fine jade
new fine
hair
oligosaccharides
jade oligosaccharides
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CN109731001B (en
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张春毅
曾润颖
侯艳平
王斐
曾翰庭
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Blue Brain Technology (xiamen) Co Ltd
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Blue Brain Technology (xiamen) Co Ltd
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Abstract

The present invention relates to composition of the new fine jade oligosaccharides as the new application of hair restorer or conditioner and comprising new fine jade oligosaccharides, more particularly to new fine jade oligosaccharides in preparation for improving and/or promoting hair growth, or elimination and/or alleviation and the purposes in the product of the bad related illness of hair growth state or state.New fine jade oligosaccharides understands for the mechanism of the purposes, clear efficacy, without side-effects, highly-safe, significant effect.Composition provided by the invention comprising new fine jade oligosaccharides has significant phalacrosis prevention and hair generation effect, nonirritant, without side-effects, highly-safe.

Description

The newly new application of fine jade oligosaccharides and the composition containing new fine jade oligosaccharides
Technical field
The present invention relates to the new application of new fine jade oligosaccharides, especially new fine jade oligosaccharides is as the active constituent for improving hair growth Effect is more particularly for preventing hair loss and promote the new application in terms of hair growth.
Background technique
Alopecia and its it is caused it is bald be a kind of common phenomenon, caused stress is to interpersonal relationships and society Life brings many puzzlements and obstacle.With the quickening pace of modern life, the increase of life stress, environmental pressure is now subjected to de- It feels sleepy the crowd disturbed increasingly rejuvenation, and not just male, female alopecia are also just gradually increasing, therefore has much for anticreep Therapeutic agent, the hair care exterior-applied article, hair tonic exterior-applied article of hair.
The reason of causing alopecia is complex, is the collective effect of many factors.The most common alopecia type is that " male swashs Plain source property alopecia ", or it is referred to as " alopecia of seborrhea type ", main reasons is that the secretion of sebum is adjusted by male sex hormone, When sebum abnormal secretion or generation exception sebum, hair health will affect, and then lead to alopecia.Current drug and hair care is used Product solve scalp oiliness issues generally by the methods of control or cleaning of male sex hormone.Such as take guarantor's method stop it is (non- That male amine piece, i.e. -5 α of N- (1,1- dimethyl ethyl) -3- oxygen -4- azepine--17 β of steroid -1- alkene-amide) inhibit male sex hormone water It is flat, promote natural on-off cycles of hair growth, treatment male sex hormone source alopecia with it is bald.Topical minoxidil (6- (1- piperidyl) -2,4- pyrimidine two Amine, 3- oxide) treatment male sex hormone source property alopecia.Although both drugs have apparent therapeutic effect, but simultaneously because drop The low level of male sex hormone, thus also produces corresponding side effect, such as erectile dysfunction, sexual hypoesthesia, and outer use occurs Fash, inflammation, itch etc..
Some cosmetics reach anticreep or hair-growing effects by addition plant extracts.Such as Chinese patent literature CN105640803A discloses anti-dandruff one kind, Anti-hair loss, hair products and preparation method thereof, is sterilized using plants essential oil anti- Bacterium, balance skin surface layer fat secretion;Chinese patent literature CN101810553A discloses a kind of trichomadesis-preventing hair-growing composition, including Each Plant Extracts such as Radix Angelicae Sinensis, the fleece-flower root, radix saposhnikoviae, kuh-seng, rhizoma zingiberis, Rhizoma Et Radix Notopterygii.According to theory of traditional Chinese medical science, they, which generally all have, dispels Wind, dehumidifying, promoting blood circulation, fall fire and other effects, but at being hard to tell the effect of these extracts, therefore its action principle is also unclear, and And these extracts easily cause the adverse reactions such as allergy, stimulation, dermatitis due to complicated component.Therefore new having is developed to protect The product that hair regrowth was sent out, and prevented hair loss, being promoted to head protector is still what those skilled in the art expected.
Marine algae extract has various functions, and polysaccharide is its key active ingredients.With enzymatic isolation method further from polysaccharide In the alga oligosaccharides that are prepared, molecular weight is small, solubility is good, has a variety of physiological activity.Such as prepared from red algae New fine jade oligosaccharides, has been found to all have physiological activity in different field, including moisturizing, the whitening etc. in skin care item;Agricultural is answered Regulating crop growth in, fresh-keeping etc.;Anti-oxidant, liver protecting, hypoglycemic, reducing blood lipid in health food etc..New fine jade is few Sugar is the oligosaccharides for extracting from red algae, how much is distinguished by the degree of polymerization, mainly includes new fine jade disaccharides, new fine jade tetrose, six sugar of new fine jade, new fine jade Eight sugar, Neoagarodecaose, Neoagarododecaose etc..But the new fine jade oligosaccharides of either one-component or mixed component, or from other The oligosaccharides of seaweed is used to protect hair, all there is not been reported for the function of hair-loss preventing and hair-restoring.
Summary of the invention
Effect the purpose of the present invention is to provide new fine jade oligosaccharides as the active constituent for improving hair growth, is especially used New application in terms of preventing hair loss and promoting hair growth.Present invention surprisingly has found that using new fine jade oligosaccharides or comprising The composition of new fine jade oligosaccharides can effectively improve hair growth state, can especially be effectively prevented alopecia and promote hair Growth.
For this purpose, in a first aspect, the present invention provides new fine jade oligosaccharides in preparation for improving and/or promote hair growth, or Person's elimination and/or alleviation and the purposes in the product of the bad related illness of hair growth state or state, wherein the new fine jade Oligosaccharides is as active constituent.
Further, the new fine jade oligosaccharides include new fine jade disaccharides, new fine jade tetrose, six sugar of new fine jade, Neoagarooctaose, Neoagarodecaose, One or more of Neoagarododecaose.In one embodiment, the new fine jade oligosaccharides be new fine jade disaccharides or new fine jade tetrose, Or newly six sugar of fine jade or Neoagarooctaose or Neoagarodecaose or Neoagarododecaose or new fine jade tetrose and six sugar of Xin Qiong or newly fine jade eight Sugar, Neoagarodecaose and Neoagarododecaose.
Further, described to refer to that alopecia or Hair growth rate are slow with the bad related illness of hair growth state or state Slowly.
Further, the alopecia refers to the property alopecia of male sex hormone source.
Further, the product is local application product.
Further, the product is used as the local application product of external preparation for skin.
Further, the product is drug or cosmetics.
Further, the product is in the form of solution, emulsus, paste, emulsifiable paste or gel.
Further, it is 0.01-1wt%, preferably 0.01- that the new fine jade oligosaccharides, which accounts for the percentage of the product total weight, 0.5wt%, more preferable 0.1-0.5wt%.
Further, the product includes: (1) new fine jade oligosaccharides, and the acceptable auxiliary material of (2) physiology.
Further, the acceptable auxiliary material of the physiology includes small molecule polyol and nonionic surfactant.
Further, the small molecule polyol is one or more of glycerol, propylene glycol, butanediol and pentanediol, excellent It is selected as glycerol.
Further, the nonionic surfactant is one or more of polyethylene glycol (PEG), tween and SPAN, Preferably PEG, further preferably PEG-400.
Second aspect, the present invention provide a kind of composition, which is characterized in that and the composition includes: (1) new fine jade oligosaccharides, (2) acceptable auxiliary material in drug or cosmetics, wherein the new fine jade oligosaccharides is to promote hair growth, improve hair condition Concentration is present in the composition, and the composition is drug or cosmetics.
Further, the new fine jade oligosaccharides include new fine jade disaccharides, new fine jade tetrose, six sugar of new fine jade, Neoagarooctaose, Neoagarodecaose, One or more of Neoagarododecaose.In one embodiment, the new fine jade oligosaccharides be new fine jade disaccharides or new fine jade tetrose, Or newly six sugar of fine jade or Neoagarooctaose or Neoagarodecaose or Neoagarododecaose or new fine jade tetrose and six sugar of Xin Qiong or newly fine jade eight Sugar, Neoagarodecaose and Neoagarododecaose.
Further, it is 0.01-1wt%, preferably 0.01- that the new fine jade oligosaccharides, which accounts for the percentage of the composition total weight, 0.5wt%, more preferable 0.1-0.5wt%.
Further, acceptable auxiliary material includes small molecule polyol and non-ionic surface active in the drug or cosmetics Agent.
Further, the small molecule polyol is one or more of glycerol, propylene glycol, butanediol and pentanediol, excellent It is selected as glycerol.
Further, the nonionic surfactant is one or more of PEG, tween and SPAN, preferably PEG, Further preferably PEG-400.
In a preferred embodiment, the glycerol accounts for the 1-6wt% of the composition total weight, preferably 1-4wt%;Institute State the 0.5-5wt% that PEG-400 accounts for the composition total weight, preferably 0.5-2wt%.
In a specific embodiment, the composition is made of new fine jade disaccharides, glycerol, PEG-400 and water.
Further, the composition is in the form of solution, emulsus, paste, emulsifiable paste or gel.
The third aspect, the present invention provide new fine jade oligosaccharides as hair restorer or the purposes of conditioner.
Further, the new fine jade oligosaccharides include new fine jade disaccharides, new fine jade tetrose, six sugar of new fine jade, Neoagarooctaose, Neoagarodecaose, One or more of Neoagarododecaose.In one embodiment, the new fine jade oligosaccharides be new fine jade disaccharides or new fine jade tetrose, Or newly six sugar of fine jade or Neoagarooctaose or Neoagarodecaose or Neoagarododecaose or new fine jade tetrose and six sugar of Xin Qiong or newly fine jade eight Sugar, Neoagarodecaose and Neoagarododecaose.
Further, new fine jade oligosaccharides is as the active constituent protected hair, prevent hair loss, and/or promote hair tonic.
Further, new fine jade oligosaccharides is as the active constituent for improving hair papilla cell vigor;In particular, new fine jade oligosaccharides is used for Improve the vigor of the damage hair papilla cell caused by androgen (such as dihydrotestosterone).
Further, new fine jade oligosaccharides is used to promote the ability of hair papilla cell secrete cytokines.
Further, new fine jade oligosaccharides is for promoting staple length growth, gross weight to increase.
New fine jade disaccharides, new fine jade tetrose, six sugar of new fine jade, Neoagarooctaose, Neoagarodecaose, Neoagarododecaose belong to new fine jade widow Sugar is a kind of oligosaccharides for extracting from red algae seaweed, can be prepared into and from red seaweed polysaccharide with enzymatic isolation method, now can passed through It is commercially available.New fine jade oligosaccharides can be used for the fields such as food, drug, cosmetics, be used to have moisturizing, anti-oxidant etc. to make when cosmetics With, but one-component or the new fine jade oligosaccharides of mixed component are for protecting the function of hair, hair-loss preventing and hair-restoring in the applying date of the invention Before have no and have been reported that.The present invention is respectively to the new fine jade oligosaccharides of one-component: new fine jade disaccharides, new fine jade tetrose, six sugar of new fine jade, new fine jade eight Sugar, Neoagarodecaose, Neoagarododecaose, and contain multi-component new fine jade oligosaccharides: new fine jade tetrose+six sugar of new fine jade, Neoagarooctaose+new fine jade Ten sugar+Neoagarododecaose, are tested respectively, and demonstrating new fine jade oligosaccharides with cell model has the function of hair-loss preventing and hair-restoring.
When new fine jade oligosaccharides is further applied animal model, the present invention is directed to skin environment (skin contains grease), choosing It is compounded with two kinds of small molecule polyol, surfactant ingredients with new fine jade disaccharides, using alcohol to the compatible spy of water and oil Property and surfactant dispersing characteristic, promote infiltration of the new fine jade disaccharides on natural skin, dispersion, make new fine jade disaccharides It can effectively play a role when for natural skin.
Small molecule polyol used in the present invention is that carbon chain lengths are 10 polyalcohols below.Small molecule for compounding is more The compatibility feature with water and oil can be selected in first alcohol, while having performance of keeping humidity, small point be usually used in drug or cosmetics Sub- polyalcohol, including glycerol, propylene glycol, butanediol, pentanediol etc.;Surfactant may include polyethylene glycol, tween, SPAN Deng.The combined factors such as use to consider according to safety, nonirritant, license, the present invention preferred glycerol and polyethylene glycol.Glycerol Compatibility feature with water and oil, facilitates the infiltration of new fine jade oligosaccharides, meanwhile, glycerol has moisture-keeping function, helps to increase hair Moisture needed for sending out eubolism;Third, glycerol are the very high drug of generally recognized as safe and cosmetic material.Polyethylene glycol is one The nonionic surfactant of kind safety helps to reduce surface tension, reinforces new fine jade oligosaccharides with glycerol in the contact of skin, promotees Into the infiltration of new fine jade oligosaccharides, the effect that new fine jade oligosaccharides promotees hair growth is given full play to.
The supplementary product kind that can be used for the compounding of new fine jade oligosaccharides is numerous, in order to provide a kind of composition be convenient for other auxiliary materials into One step compounding forms various products, and the present invention is preferably a kind of to have anticreep by what new fine jade disaccharides, glycerol, PEG-400 and water formed The composition for educating hair effect, can be applied to the raw material of hair products, can also use directly as hair products.
To sum up, compared with prior art, the invention has the following advantages that
(1) the present invention provides the new application of new fine jade oligosaccharides, new fine jade oligosaccharides is used for highly-safe, the nothing of hair-loss preventing and hair-restoring effect It is side effect, nonirritant.And the existing product for hair-loss preventing and hair-restoring mainly has Finasteride, minoxidil and plant extract Object, Finasteride and minoxidil side effect are strong;Plant extracts is also easy to produce irritation due to complicated component.
(2) new fine jade oligosaccharides understand for the mechanism of hair-loss preventing and hair-restoring effect, clear efficacy, confirm that new fine jade oligosaccharides can for the first time Alleviate dihydrotestosterone to the inhibiting effect of hair papilla cell, improves the vigor of hair papilla cell.It is widely used in the prior art Plant extracts complicated component, some components even have bad or negative effect to hair-growing and hair care, reduce hair-loss preventing and hair-restoring Effect, extract effect is unstable between not only resulting in different batches, and has raised cost, caused waste.
(3) the present invention provides a kind of compositions comprising new fine jade oligosaccharides, have protection hair, prevent hair loss, promote life The effect of hair, the composition be used for phalacrosis prevention and hair generation when obvious effect, nonirritant, without side-effects, safety is good.
Detailed description of the invention
By reading the following detailed description of the preferred embodiment, various other advantages and benefits are common for this field Technical staff will become clear.The drawings are only for the purpose of illustrating a preferred embodiment, and is not considered as to the present invention Limitation.And throughout the drawings, the same reference numbers will be used to refer to the same parts.In the accompanying drawings:
Fig. 1 is influence of the various concentration DHT to hair papilla cell vigor;
Fig. 2 is influence of the new fine jade oligosaccharides of different polymerization degree and various concentration to hair papilla cell vigor
When Fig. 3 is that the new fine jade oligosaccharides of different polymerization degree acts on androgens psilosis In vitro cell model, the expression to VEGF Amount influences;
Fig. 4 is DHT when acting on hair papilla cell, to DKK-1, TGF-β 2, β-catenin and AR expression quantity influence
When Fig. 5 is that new fine jade disaccharides (DP2) acts on androgens psilosis In vitro cell model, to DKK-1, TGF-β 2, β- The expression quantity of catenin and AR influences;
Fig. 6 is agartose -4, 6 (DP4-6) when acting on androgens psilosis In vitro cell model, to DKK-1, TGF-β 2, The expression quantity of β-catenin and AR influences;
Fig. 7 is that Neoagarooctaose, Neoagarodecaose and Neoagarododecaose (DP8-12) act on androgens psilosis cell in vitro mould When type, the expression quantity of DKK-1, TGF-β 2, β-catenin and AR are influenced;
Fig. 8 is the transdermal penetration result of new fine jade disaccharides and combinations thereof.
Specific embodiment
The illustrative embodiments of the disclosure are more fully described below with reference to accompanying drawings.Although showing this public affairs in attached drawing The illustrative embodiments opened, it being understood, however, that may be realized in various forms the disclosure without the reality that should be illustrated here The mode of applying is limited.It is to be able to thoroughly understand the disclosure on the contrary, providing these embodiments, and can be by this public affairs The range opened is fully disclosed to those skilled in the art.
The present invention carries out general and/or specific description to material and test method used in test, under In the embodiment in face, if without other special explanations, % indicates wt%, i.e. weight percent.Agents useful for same or instrument are not infused Bright production firm person, being can be by the conventional reagent product of commercially available acquisition.
Effect of the new fine jade oligosaccharides of embodiment 1 to androgens psilosis In vitro cell model
Using hair papilla cell as subjects, androgens psilosis body is established with certain density dihydrotestosterone (DHT) stimulation Then outer cell model passes through inspection using minoxidil as positive control with new fine jade oligosaccharides processing androgens psilosis external model Survey vascular endothelial growth factor (VEGF), DKK-1, transforming growth factor (TGF-β 2) and the β-chain of rings of hair papilla cell secretion The variation of albumen (β-catenin), androgen receptor (AR) content is come the effect of evaluating new fine jade oligosaccharides promotion hair regeneration.
The new fine jade oligosaccharides that the present embodiment is used has following three kinds: (1) new fine jade disaccharides (DP2);(2) new fine jade tetrose and Xin Qiong six Sugared (DP4-6), wherein the ratio of new fine jade tetrose is 55%, the ratio of new six sugar of fine jade is 45%;(3) Neoagarooctaose, Neoagarodecaose With Neoagarododecaose (DP8-12), wherein the ratio of Neoagarooctaose is 45%, and the ratio of Neoagarodecaose is 30%, Neoagarododecaose Ratio be 25%
Specific test procedure is as follows:
(1) androgens psilosis external model is constructed
Using hair papilla cell as research object, hair papilla cell is handled with the dihydrotestosterone (DHT) of various concentration, by thin Born of the same parents' vigor, cell factor VEGF, TGF-β 2, β-catenin, DKK1 and androgen receptor AR situation of change determine DHT Optimal stimulus concentration, wherein DHT optimal stimulus concentration be under the premise of not damaging cells (cell viability >=90%), can make The concentration of conspicuousness variation (P < 0.01) occurs for the expression quantity of several secretion factors.Specific step is as follows:
(1) by hair papilla cell with 1.5 × 105The inoculum density of/hole cell is seeded in 96 orifice plates, is placed in 37 DEG C, Containing 5%CO2Incubator is incubated for for 24 hours;
(2) cell culture fluid cultivated for 24 hours is discarded, culture solution is more renewed, while being separately added into the DHT of various concentration (0nM, 25nM, 50nM, 100nM, 200nM, 400nM, 600nM, 800nM, 1000nM), culture is for 24 hours;
(3) cell viability detects: after step (2) culture, discarding supernatant, the MTT that 200 μ L concentration are 0.5mg/mL is added Working solution, 37 DEG C are protected from light incubation.It is discarded supernatant after 4h, every hole adds 150 μ L dimethyl sulfoxides, reads OD using microplate reader490Value. With the cell OD value of blank control (0nM DHT is added) for 100% cell viability, cell viability value is calculated, through various concentration DHT Cell viability value is shown in Fig. 1 after processing.
As shown in Figure 1, when the concentration of dihydrotestosterone (DHT) is not higher than 800nM, the vigor of hair papilla cell is maintained 90% or more, when DHT concentration reaches 1000nM, cell viability is down to 82.26%.And DHT concentration be 800nM when, before can making Conspicuousness variation (P < 0.01) occurs for five kinds of expression quantity for stating secretion factor, and the best thorn of DHT is selected according to the above experimental result Swashing concentration is 800nM.
(2) cytotoxicity of the new fine jade oligosaccharides to hair papilla cell of different polymerization degree is detected
The new fine jade oligosaccharides for detecting various concentration by mtt assay filters out the peace of sample to the toxic effect of hair papilla cell Full working concentration range carries out subsequent efficacy assessment experiment.Detection method is as follows:
Table is arranged in the new fine jade oligosaccharide concentration of table 1
(1) cell culture fluid is added into 96 orifice plates, with 1.5 × 105The inoculum density of/hole cell is seeded to 96 orifice plates In, 37 DEG C are placed in, 5%CO is contained2Incubator is incubated for for 24 hours;
(2) match liquid: being prepared with cell culture fluid: experimental group: the concentration recorded according to table 1 respectively will with culture solution The new fine jade oligosaccharides (DP2, DP4-6, DP8-12) of different polymerization degree is configured to required concentration;Positive controls (PC group): it prepares Culture solution containing 4%DMSO;Blank group: it is without any processing to culture solution, for use;
(3) it is administered: discarding the cell culture fluid cultivated for 24 hours, be separately added into step (2) and prepare obtained experimental group culture Liquid, PC group culture solution, blank group culture solution continue culture for 24 hours;
(4) detect: cell incubation for 24 hours after, discard supernatant, be added 200 μ L concentration be 0.5mg/mL MTT working solution, 37 It DEG C is protected from light incubation, is discarded supernatant after being incubated for 4h, every hole adds 150 μ L dimethyl sulfoxides, reads OD with microplate reader490Value.With blank pair According to cell OD value be 100% cell viability, experiment with computing group and PC group cell viability value, cytotoxicity testing result such as table 2; Fig. 2 is shown in influence of the new fine jade oligosaccharides of various concentration to hair papilla cell vigor.
2 cytotoxicity testing result of table
From cytotoxicity result (table 2, Fig. 2) it is found that the new fine jade oligosaccharides of different polymerization degree is to the vigor shadow of hair papilla cell It rings quite, when its concentration is within the scope of 5000ppm, the vigor of hair papilla cell maintains 90% or more, when its concentration reaches When 10000ppm, cell viability is down to 90% or less.According to this as a result, maximum safety of the new fine jade oligosaccharides on hair papilla cell is given Concentration is 5000ppm, it is final determine selected in the safe administration concentration range of new fine jade oligosaccharides 200ppm, 1000ppm and These three concentration of 5000ppm are administered hair papilla cell.
(3) effect of the new fine jade oligosaccharides to androgens psilosis In vitro cell model is tested
By hair papilla cell with 1.5 × 105The inoculum density of/hole cell is seeded in 6 orifice plates, is placed in 37 DEG C, contains 5% CO2Incubator is incubated for for 24 hours.Blank control group is without any processing, and negative control group (NC) is added 800nM DHT and is stimulated, 500 μM of minoxidils are added simultaneously for positive controls (PC) and 800nM DHT and difference is added simultaneously in 800nM DHT, experimental group The new fine jade oligosaccharides of the degree of polymerization continues to be incubated for for 24 hours, supernatant and cell is collected respectively, using in ELISA method detection supernatant VEGF;Cell is collected, using RT-PCR detection DKK-1, TGF-β 2, β-catenin and AR.Make using Graph Pad Prism Figure, is as a result expressed as Mean ± SD.
The testing result of VEGF is shown in Fig. 3, and when for statistical analysis with T-Test method, NC group is compared with blank, conspicuousness It is indicated with #, P-value < 0.05 is expressed as #, and P-value < 0.01 is expressed as ##;Each experimental group and PC group compared with NC group, Conspicuousness indicates that P-value < 0.05 is expressed as * with *, and P-value < 0.01 is expressed as * *.
DKK-1, TGF-β 2, the testing result of β-catenin and AR are shown in Fig. 4-Fig. 7.Using 2-△△CTMethod carries out result meter It calculates, when for statistical analysis with T-Test method, in Fig. 4, by blank group mRNA amplification times normalization, NC group and blank Group is compared, and conspicuousness is indicated with #, and P-value < 0.05 is expressed as #, and P-value < 0.01 is expressed as ##.In Fig. 5-Fig. 7, By NC group mRNA amplification times normalization, compared with NC group, conspicuousness is indicated with * for PC group and each experimental group, P-value < 0.05 is expressed as *, and P-value < 0.01 is expressed as * *.
As can be seen from Figure 3, compared to the blank group, the VEGF secretory volume of NC group significantly reduces, and illustrates this experiment DHT incentive condition Effectively.Compared with NC group, three concentration of new fine jade oligosaccharides DP2 are obviously improved effect to the secretory volume of VEGF in experimental group, And with the raising of new fine jade disaccharides concentration, promotion effect is more significant, and when its concentration reaches 5000ppm, VEGF content is even super Minoxidil is crossed;And new fine jade oligosaccharides DP4-6 and DP8-12 does not have the secretory volume of VEGF under the conditions of low concentration (200ppm) It significantly affects, when the concentration of the two improves, the secretory volume of VEGF is also significantly improved.This illustrate new fine jade oligosaccharides DP2, DP4-6 and DP8-12 can promote the secretion of VEGF in hair papilla cell, effectively release DHT to the inhibiting effect of cell, and DP2 ratio DP4-6's and DP8-12 performs better.
As can be seen from Figure 4, compared to the blank group, the DHT of 800nM has the expression of hair papilla cell beta-catenin gene aobvious Write inhibiting effect;Effect is obviously improved to the expression of hair papilla cell TGF β 2, DKK1 and AR gene, illustrates this experiment DHT Incentive condition is effective.
As can be seen from Figure 5, new fine jade oligosaccharides DP2 can stimulate the expression and suppression of beta-catenin gene in androgens psilosis model The expression of TGF-β 2, DKK1 and AR receptor processed, expression quantity have significant difference compared with negative control group.As can be seen from Figure 6, new fine jade Oligosaccharides DP4-6 has a conspicuousness inhibiting effect to the expression of TGF-β 2, DKK1 and AR receptor, and the expression to beta-catenin gene It does not make significant difference.As can be seen from Figure 7, new fine jade oligosaccharides DP8-12 has conspicuousness inhibiting effect to the expression of DKK1 and AR receptor, and right The expression of 2 gene of β-catenin and TGF-β does not make significant difference.
In summary it analyzes, new fine jade oligosaccharides androgens psilosis model caused by DHT of three kinds of degree of polymerization has reparation to imitate The effect of fruit can improve the expression quantity of secretion factor related with alopecia in model, show hair-loss preventing and hair-restoring, wherein with new fine jade two The performance of sugared (DP2) is optimal, has a significant impact to VEGF, β-catenin, TGF-β 2, DKK1 and AR, new fine jade oligosaccharides DP4- The effect of 6 and DP8-12 takes second place (influence to part index number is not significant).Therefore it is preferred that new fine jade disaccharides is as trichomadesis-preventing hair-growing composition Main active.
The test of 2 transdermal penetration of embodiment
Transdermal penetration test is intended to investigate the permeability of new fine jade disaccharides on the skin, due to the barrier action of cell, uses The new fine jade disaccharides of high concentration guarantees the accuracy of detection with the content of new fine jade disaccharides in sample after raising infiltration.Simultaneously design to Glycerol and nonionic surface active agent (such as polyethylene glycol) are added to enhance its percutaneous absorbtion performance in new fine jade disaccharides, are promoted The selection of penetration enhancer and concentration design are as shown in table 3.
The selection of 3 penetrating agent of table and concentration design
Combination 1 1% new fine jade disaccharides
Combination 2 1% new+1% glycerol of fine jade disaccharides
Combination 3 1% new+2% glycerol of fine jade disaccharides
Combination 4 1% new fine jade disaccharides+1%PEG400
Combination 5 1% new fine jade disaccharides+2%PEG400
Combination 6 1% new+1% glycerol+1%PEG400 of fine jade disaccharides
Combination 7 1% new+2% glycerol+1%PEG400 of fine jade disaccharides
The SD rat skin handled well is fixed in the diffusion cell of transdermal diffusion apparatus (RYJ -12B type).It takes containing 1% The 500 μ L of physiological saline of new fine jade disaccharides is added dropwise on rat skin, avoiding generating bubble.On supply room plus preservative film prevents moisture from steaming Hair.6mL physiological saline is added in reception tank, recirculated water keeps 37 (± 0.5) DEG C, mixing speed 300rpm.Respectively at infiltration 0.5, extracting whole liquid when 1,2,3,4,5h from reception tank, to be placed in 4 DEG C to be measured, while supplementing equivalent etc. into reception tank again The fresh physiological salt water of temperature, three repetitions of experimental setup.By aforesaid operations process to the new fine jade disaccharides containing different penetrating agents Percutaneous absorptivity is measured.All samples to be tested are concentrated into 1mL with Rotary Evaporators, are measured using DNS method wherein new The content of fine jade disaccharides and the infiltration capacity of unit of account area.The transdermal penetration result of new fine jade disaccharides and combinations thereof is shown in Fig. 8.
As shown in Figure 8, individually new fine jade disaccharides infiltration slowly, when being separately added into glycerol and non-ionic surface active thereto After agent, mechanism is obvious, and when glycerol and PEG400 are existed simultaneously, mechanism is than individual glycerol or PEG400 It is good, wherein 7 (2% glycerol+1%PEG400) of combination show optimal mechanism, make new fine jade disaccharides rapidly and efficiently through dynamic Object skin.
3 mouse hair tonic of embodiment test
Cavy 18 are taken, is randomly divided into 3 groups (blank group tests 1 group, tests 2 groups), every group 6, wherein blank group is made a living Salt water group is managed, 1 group of new fine jade disaccharides group (containing the new fine jade disaccharides of 5000ppm) is tested, 2 groups of test are composition group (the new fine jade of 5000ppm + 2% glycerol+1%PEG400 of disaccharides).Give cavy to inject appropriate anesthetic, after its anesthesia, by every back same area 3 × 3cm2Chaeta it is cleared, be careful not to damage skin cavy is put back in cage with physiological saline wiped clean.After for 24 hours, removing Hair-fields administration, every 500 μ L are smeared uniformly, 1 time a day, continuous 30 days, and at random from cavy administration portion behind 30 days of administration Position 10 chaetas of clip, measure its length and weight, using its average value as Indexes Comparison each group cavy body hair growth situation, measure The hair-growing effects of mouse are shown in Table 4.
Hair-growing effects of the new fine jade disaccharides of table 4 and combinations thereof to mouse
As seen from the above table, compared with physiological saline, new fine jade disaccharides and combinations thereof has the hair growth of depilation mouse Apparent facilitation.And the composition containing glycerol and polyethylene glycol, hair-growing effects are more obvious, 30 days staple length growth rates Reach 53.5%, gross weight increases by 56.8%.This explanation, the substances such as glycerol and polyethylene glycol can effectively facilitate new fine jade disaccharides in skin Diffusion in tissue, the composition have significant promotion hair growth effect.
The foregoing is only a preferred embodiment of the present invention, but scope of protection of the present invention is not limited thereto, In the technical scope disclosed by the present invention, any changes or substitutions that can be easily thought of by anyone skilled in the art, It should be covered by the protection scope of the present invention.Therefore, protection scope of the present invention should be with the protection model of the claim Subject to enclosing.

Claims (10)

1. new fine jade oligosaccharides is in preparation for improving and/or promoting hair growth, or elimination and/or alleviation and hair growth state Purposes in the product of bad related illness or state, wherein the new fine jade oligosaccharides is as active constituent.
2. purposes according to claim 1, which is characterized in that described and the bad related illness of hair growth state or shape State refers to that alopecia or Hair growth rate are slow.
3. purposes according to claim 1 or 2, which is characterized in that the product is local application product.
4. purposes according to claim 1 or 2, which is characterized in that the new fine jade oligosaccharides accounts for the hundred of the product total weight Score is 0.01-1wt%.
5. purposes according to claim 1 or 2, which is characterized in that the product includes the acceptable auxiliary material of physiology, institute Stating the acceptable auxiliary material of physiology includes small molecule polyol and nonionic surfactant.
6. a kind of composition, which is characterized in that the composition includes: (1) new fine jade oligosaccharides, and can in (2) drug or cosmetics The auxiliary material of receiving, wherein the new fine jade oligosaccharides is to promote the concentration of hair growth, improvement hair condition to be present in the composition In, the composition is drug or cosmetics.
7. composition according to claim 6, which is characterized in that the new fine jade oligosaccharides accounts for the hundred of the composition total weight Score is 0.01-1wt%.
8. composition according to claim 6 or 7, which is characterized in that acceptable auxiliary material in the drug or cosmetics Including small molecule polyol and nonionic surfactant.
9. composition according to claim 8, which is characterized in that the small molecule polyol is glycerol, propylene glycol, fourth two One or more of pure and mild pentanediol;The nonionic surfactant is one or more of PEG, tween and SPAN.
10. new fine jade oligosaccharides is as hair restorer or the purposes of conditioner, wherein new fine jade oligosaccharides is for improving hair papilla cell vigor, it is special It is not that new fine jade oligosaccharides is used to improve the vigor of the damage hair papilla cell caused by androgen (such as dihydrotestosterone).
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CN112369608A (en) * 2019-12-27 2021-02-19 青岛博智汇力生物科技有限公司 A weight reducing food containing marine oligosaccharide
CN113881729A (en) * 2021-11-09 2022-01-04 蓝脑科技(厦门)有限公司 Production method of neoagarobiose
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CN110538193A (en) * 2019-09-06 2019-12-06 蓝脑科技(厦门)有限公司 Application of carrageenan oligosaccharide and composition containing carrageenan oligosaccharide
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CN111110581A (en) * 2019-12-31 2020-05-08 蓝脑科技(厦门)有限公司 Novel agaro-oligosaccharide composition with whitening function improving function and application thereof
CN111110590A (en) * 2019-12-31 2020-05-08 蓝脑科技(厦门)有限公司 Agar oligosaccharide composition for balancing scalp grease secretion, preparation method and application
CN111419748A (en) * 2019-12-31 2020-07-17 蓝脑科技(厦门)有限公司 Seaweed oligosaccharide composition with function of repairing skin after being exposed to sun, preparation method and application thereof
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CN111110581B (en) * 2019-12-31 2022-09-27 蓝脑科技(厦门)有限公司 Novel agaro-oligosaccharide composition with whitening function improving function and application thereof
CN113881729A (en) * 2021-11-09 2022-01-04 蓝脑科技(厦门)有限公司 Production method of neoagarobiose
CN113881729B (en) * 2021-11-09 2023-06-27 蓝脑科技(厦门)有限公司 Production method of neoagalloch disaccharide
CN114306197A (en) * 2022-01-17 2022-04-12 广州温雅日用化妆品有限公司 Bubble hair conditioner

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