CN102994558B - Manufacturing method of ceramide production promoter - Google Patents

Manufacturing method of ceramide production promoter Download PDF

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Publication number
CN102994558B
CN102994558B CN201110289082.2A CN201110289082A CN102994558B CN 102994558 B CN102994558 B CN 102994558B CN 201110289082 A CN201110289082 A CN 201110289082A CN 102994558 B CN102994558 B CN 102994558B
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ceramide
schizosaccharomyces
glucose
production accelerant
ceramide production
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CN201110289082.2A
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CN102994558A (en
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孔凡旗
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Kao Corp
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Kao Corp
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Priority to JP2013522070A priority patent/JP5639713B2/en
Priority to PCT/CN2011/001877 priority patent/WO2012062043A1/en
Publication of CN102994558A publication Critical patent/CN102994558A/en
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Abstract

The invention provides a manufacturing method of a ceramide production promoter and/or a glucose ceramide production promoter, wherein the ceramide production promoter and/or the glucose ceramide production promoter is obtained from supernatant fluid of a microorganism of Schizosaccharomyces, which is cultured in a culture medium containing bean dregs and saccharides. According to the manufacturing method disclosed by the invention, substances which are easy to obtain can be used as the culture medium, the specific microorganism can be further utilized, and then the ceramide production promoter and/or the glucose ceramide production promoter can be obtained at a low cost with high efficiency.

Description

The manufacture method of ceramide production accelerant
Technical field
The present invention relates to promote skin to produce ceramide and/or the ceramide production accelerant of glucose ceramide and/or the manufacture method of glucose ceramide production accelerant.
Background technology
Skin has the ability of generation ceramide (ceramide) and glucose ceramide (glucosylceramide).In skin, particularly assembling the ceramide being obtained by epidermic cell synthesis secretion in horny layer of epidermis, it is the main component of intercellular lipid.And be temporarily stored with the form of glucose ceramide or sphingomyelin (sphingomyelin) by the synthetic ceramide obtaining of epidermic cell; Be discharged to afterwards extracellular, under the effect of glucose cerebrosidase (glucocerebrosidase) and sphingomyelinase (sphingomyelinase), again form ceramide, thereby performance is as the function of intercellular lipid.Ceramide in skin and glucose ceramide have the physiological action that improves the moisture-keeping functions of skin and the barrier function of skin etc.
But recently, due to the impact of environment, weather etc., it is dry that skin easily becomes, therefore produce by skin self moisture-keeping functions that ceramide etc. improves skin and just seem not enough.
Thereby people have attempted supplementing to skin from outside the method for ceramide.For example, in patent documentation 1, record microorganism that cultivation candiyeast (Candida) belongs to and manufactured the method for glucose ceramide, by this glucose ceramide being coated on to the moisture-keeping functions that can improve skin on the drying property skin of human body.The method is directly from the thalline cultivation, to obtain the glucose ceramide of a large amount of existence, therefore the ceramide skeleton of the glucose ceramide of synthesized is different with the ceramide skeleton of the ceramide type existing in human body, and it has carbon-carbon double bond and have side chain at Liang Chu.Therefore, this glucose ceramide obtaining that directly extracts from microorganism is coated on human body skin, likely can not adapts with human body skin and produce the problem of safety in utilization aspect.
In addition, from outside to the same inadequate problem of persistence that has humidity-holding effect such as the method for the supplementary ceramide of skin and the wetting Agent for Printing Inks of use in the past, and the skin of some state is insufficient to the absorption of ceramide from extraneous supply etc., thereby cause giving full play to humidity-holding effect.
And on the other hand, if can strengthen or promote the generation ability of ceramide or the glucose ceramide of skin itself, without from external complement ceramide or glucose ceramide, and can improve by promoting skin self to produce ceramide and/or glucose ceramide barrier function and the moisture-keeping functions of skin.Like this, because being produces ceramide or glucose ceramide by skin self, synthesized be the ceramide etc. of the conventional structure that has of skin, thereby there is not the safety issue bad etc. with the adaptability of skin in it.
Therefore recently quite popular about the research of material that produces the generation that promotes epidermis ceramide etc. in keratoderma.Wherein, as the material that can promote that ceramide generates, that has reported has a ceramide production accelerant (patent documentation 2~4) taking the extract of glossy ganoderma, bee pollen (Bee Pollen), Ligusticum wallichii etc. as effective constituent.But because these ceramide production accelerants are all to extract and obtain from plant material, it extracts and operates the length that expends time in, and restricted aspect the utilizability of natural resource, thereby its manufacturing cost is high.
In addition, in patent documentation 5, a kind of synthetic ceramide synthesis accelerators of ceramide of the epidermic cell self that can activate skin surface inside is disclosed, it is taking the bacterium culture that contains nicotinic acid and/or niacinamide as effective constituent, and this bacterium culture can be lactic acid bacteria culture, bifidobacterium culture, mushroom thalline culture or Yeast culture.But the substratum using in the preparation process of this promotor is in fact using nicotinic acid and/or niacinamide as effective constituent, therefore the preparation cost of this ceramide synthesis accelerators is higher.
In addition, Schizosaccharomyces (Schizosaccharomyces) yeast is used in food-processing all the time, and its fermentation produces ethanol, and is also used as biological research material.
But, also do not utilize fission yeast to prepare the report of ceramide production accelerant or glucose ceramide production accelerant at present.
Patent documentation 1: TOHKEMY 2010-22217 communique
Patent documentation 2: TOHKEMY 2005-194240 communique
Patent documentation 3: TOHKEMY 2010-70499 communique
Patent documentation 4: TOHKEMY 2010-150237 communique
Patent documentation 5: Japanese kokai publication hei 9-194383 communique
Summary of the invention
The present invention makes in order to solve the technical problem existing in above-mentioned prior art, and object is to provide a kind of low cost and manufactures efficiently ceramide production accelerant and/or the method for glucose ceramide production accelerant.
The inventor has carried out wholwe-hearted research in order to solve the problems of the technologies described above, found that: in the substratum that contains bean dregs and carbohydrate, cultivate the microorganism of Schizosaccharomyces (Schizosaccharomyces), can obtain efficiently ceramide production accelerant and/or glucose ceramide production accelerant; Thereby complete the present invention.
The invention provides the manufacture method of a kind of ceramide production accelerant and/or glucose ceramide production accelerant, wherein, in the substratum that contains bean dregs and carbohydrate, cultivate the microorganism of Schizosaccharomyces (Schizosaccharomyces), in clear liquid, obtain from it ceramide production accelerant and/or glucose ceramide production accelerant.
Manufacturing method according to the invention, can use specific microorganism and utilize the material of the so easy acquisition of bean dregs as the main raw material of substratum, thereby can be cheap and obtain efficiently ceramide production accelerant and/or glucose ceramide production accelerant, this promotor can effectively be improved the ability of generation ceramide/glucose ceramide that skin has, thereby effectively improves the moisture-retaining capacity of skin.
Embodiment
Manufacture method of the present invention is in the substratum that contains bean dregs and carbohydrate, to cultivate the microorganism of Schizosaccharomyces, and in clear liquid, obtains ceramide production accelerant and/or glucose ceramide production accelerant from it.
As the microorganism of the Schizosaccharomyces (Schizosaccharomyces) that use in the present invention, can list eight spore fission yeasts (Schizosaccharomyces octoporus), schizosaccharomyces pombe (Schizosaccharomycespombe) etc. conventional in field of food industry.
Wherein, the viewpoint from obtained product with higher ceramide generation facilitation effect and/or glucose ceramide generation facilitation effect is considered, preferably eight spore fission yeasts (Schizosaccharomyces octoporus).
The microorganism of Schizosaccharomyces (Schizosaccharomyces) involved in the present invention can be bought and obtain from commercial channel such as Chinese common micro-organisms preservation administrative center (CGMCC), Chinese Typical Representative culture collection center (CCTCC), Chinese Universities ' industrial microorganism resource and information centers (CICIM:Culture & Information Center of Industrial Microorganism of China Universities).
In manufacture method of the present invention, can use separately a kind of mentioned microorganism, also can combine mentioned microorganism of more than two kinds and use.
The substratum using in the present invention is the substratum that contains bean dregs and carbohydrate.Bean dregs and carbohydrate are all the materials easily obtaining, thereby substratum of the present invention has advantages of that cost is low.And, in addition, also can suitably add for example 1% peptone, 0.5% yeast powder etc.
Wherein, bean dregs refer to, pulverize after soybeans soaking being made in water it fully absorb moisture, more after filtration, the material that dewaters, drain and obtain.Also can use residual Soybeanresidue in the bean product manufacturing process of squeezing soya-bean milk etc. in food industries.
Carbohydrate can be glucose, sucrose, maltose etc., and they can use separately arbitrarily or mix use.And the viewpoint that produces facilitation effect and glucose ceramide generation facilitation effect from improving ceramide is considered, wherein preferred glucose.
The viewpoint that produces facilitation effect and glucose ceramide generation facilitation effect from improving ceramide is considered, medium optimization of the present invention is made up of bean dregs, glucose and water, further in preferred culture medium, the content of bean dregs is 5~20w/v%, more preferably 8~12w/v%, and the content of glucose is 0.2~2w/v%, more preferably 0.8~1.2w/v%.
Above-mentioned cultivation is preferably carried out in the viewpoint consideration that produces facilitation effect and glucose ceramide generation facilitation effect from physiological property and the raising ceramide of Schizosaccharomyces (Schizosaccharomyces) microorganism at 27~35 DEG C.
The viewpoint consideration that produces facilitation effect and glucose ceramide generation facilitation effect from physiological property and the raising ceramide of Schizosaccharomyces (Schizosaccharomyces) microorganism, above-mentioned incubation time is preferably 1~7 day, more preferably 48~96 hours, more preferably 68~76 hours.
From obtaining the viewpoint of purer product, thereby preferably the culture obtaining by described cultivation is further refined and obtained supernatant liquor.As refining method, the appropriately combined conventional operation with filtration, centrifugation, ion-exchange or adsorption chromatography, solvent extraction, crystallization etc. is carried out as required.Preferably obtain supernatant liquor by centrifugation, the speed of this centrifugation is preferably 2000~4000rpm, 2500~3500rpm more preferably, and centrifugation time is preferably 0~20 minute, more preferably 5~15 minutes.
Can in the above-mentioned supernatant liquor of centrifugal rear acquisition, add ethanol, be used for carrying out sterilizing, and will add the supernatant liquor of ethanol as ceramide production accelerant and/or glucose ceramide production accelerant.
Also can from nutrient solution, remove by centrifugation thalline, then ultrasonication, centrifugation, reclaims supernatant liquor.Then, then by reclaim after supernatant liquid filtering remove impurity etc., under vacuum after drying treatment as ceramide of the present invention and/or glucose ceramide production accelerant.
By the Soybeanresidue fermented product extract of cultivating Schizosaccharomyces of the present invention (Schizosaccharomyces) microorganism and obtaining, there is the effect that makes the amount of ceramide and/or glucose ceramide increase in normal human's keratinocyte from culture supernatant.
Therefore, the Soybeanresidue fermented product extract obtaining from culture supernatant by cultivating Schizosaccharomyces of the present invention (Schizosaccharomyces) microorganism, can be for promoting ceramide and/or the therapeutic purpose of glucose ceramide generation or the use of non-therapeutic purpose, the ceramide production accelerant and/or the glucose ceramide production accelerant that also can be used as therapeutic purpose or non-therapeutic purpose use.The use of non-therapeutic purpose is that to improve looks be the use of object, or for maintaining the use etc. of state of health.And the use of described therapeutic purpose and the use of non-therapeutic purpose can completely be carried out with distinguishing.
By the Soybeanresidue fermented product extract of cultivating Schizosaccharomyces of the present invention (Schizosaccharomyces) microorganism and obtaining from culture supernatant, also can be for the manufacture of ceramide production accelerant and/or glucose ceramide production accelerant.
Ceramide production accelerant of the present invention and/or glucose ceramide production accelerant can be used as the ceramide that makes in stratum corneum and/or glucose ceramide to be increased and recovers and improve the uses such as the barrier function of skin and the pharmaceuticals of moisture-keeping functions, accurate pharmaceuticals, makeup.In addition, this ceramide production accelerant or glucose ceramide production accelerant also can be used as taking ceramide generation promotion or glucose ceramide and produce promotion as accurate pharmaceuticals concept, that also indicate as required this concept, makeup use.
As the use form of ceramide production accelerant of the present invention and/or glucose ceramide production accelerant, can be the additive for adding to culturing cell, can be to be also coupled in the external composition for skin such as skin cleaning agent, makeup to use.For example, can enumerate the various forms such as astringent, emulsion, gel, frost, ointment.And as the base of external preparation, as long as known external application base, be not particularly limited.In the time of the various external composition for skin of preparation, can use individually ceramide production accelerant of the present invention and/or glucose ceramide production accelerant, or with appropriately combined use the such as the oiliness composition conventionally coordinating in the external composition for skin such as skin cleaning agent and makeup, wetting Agent for Printing Inks, powder, pigment, emulsifying agent, solubilizing agent, UV light absorber, thickening material, effective component, spices, fungi-proofing mould inhibitor, plant milk extract, alcohols.
Ceramide production accelerant of the present invention and/or glucose ceramide production accelerant are added in the epidermic cell of cultivation and promote in the situation of ceramide and/or glucose ceramide, addition as the dry thing of this promotor is preferably 0.0001~10w/v%, more preferably 0.001~5w/v%.When addition is 0.0001w/v% when above, can obtain sufficient facilitation effect; And when addition be below 10w/v% time, less to the pungency of epidermic cell.
When ceramide production accelerant of the present invention and/or glucose ceramide production accelerant are engaged in to external composition for skin and use, thereby effectively improve the moisture-retaining capacity of skin and be difficult for demonstrating the color of culture and the viewpoint of smell from the generation of effective promotion ceramide and/or glucose ceramide, its use level is preferably 0.01~20w/v% of external composition for skin total amount, more preferably 0.1~10w/v%.
Embodiment
Below, based on embodiment, the present invention will be described in more detail, but the present invention is not limited thereto.
Embodiment 1
Preparation (fermentation liquor treatment) > of < ceramide/glucose ceramide production accelerant
First, prepare in accordance with the following methods substratum: soybean is put into water and soaks 12 hours, make soybean fully absorb moisture, then will absorb the soybean of moisture grind brokenly, by its filtration and remove liquid component, residual residue drains, and obtains bean dregs.These bean dregs are mixed with glucose and water, and make bean dregs and the glucose concentration in mixture reach respectively 10w/v% and 1w/v%, using this mixture as substratum.
Then, the above-mentioned substratum of 100ml is added in Erlenmeyer flask, inoculate a certain amount of eight spore fission yeasts (Schizosaccharomyces octoporus) and (be preserved in Chinese Universities ' industrial microorganism resource and the CICIM of information center, numbering CICIM Y0123), at 30 DEG C, cultivate 3 days.
Then by obtained culture centrifugation (3000rpm, 10 minutes).Residue supernatant liquor adds the dehydrated alcohol dilution of 2.5 times, mixed solution after this dehydrated alcohol dilution is carried out to supersound process 10 minutes, centrifugal (3000rpm) 30 minutes, collect supernatant liquor (about 70ml), supernatant liquor obtains filtrate with filter paper filtering, filtrate is dried to constant weight in Vacuumdrier, using this dry product as ceramide of the present invention and/or sample A, the B of glucose ceramide production accelerant, the solution that sample A, B is mixed with respectively to 1%, 0.1% concentration with 50% dissolve with ethanol, is stored in 4 DEG C of refrigerators as cell cultures additive.
The evaluation > of < ceramide/glucose ceramide production accelerant
(cell cultures)
First the activation keratinocyte (Cascade Co., Ltd) of, getting normal people is as primary cell, in 75cm 2in culturing bottle (the substratum 2ml that contains somatomedin), 37 DEG C, CO 2concentration is culturing cell to 80~90% concentration under 5% condition.Go down to posterity, passage cell is to 175cm 2in square vase, continue culturing cell to 80~90% concentration.Then the human epidermal cell after going down to posterity is inoculated in 12 orifice plates, every pore volume is 2ml, and cell concn is 1 × 10 5individual cell/ml, continues culturing cell to 80~90% concentration.
Then, in above-mentioned 12 orifice plates, change the substratum that does not contain somatomedin, sample A, B and reference substance (aqueous ethanolic solution that concentration is 50v/v%) are added respectively in above-mentioned 12 orifice plates (n=2), under same culture conditions, cultivate 3 days.
After within 3 days, cultivating, supernatant discarded nutrient solution, with 2ml PBS (phosphate buffered saline buffer), cell being carried out to 2 times cleans, add again the PBS of 1ml to plate hole, to test tube, prepare against follow-up ceramide/glucose ceramide and protein analysis with cell harvestor (cell shovel) collecting cell.
(ceramide/glucose ceramide produces the confirmation of facilitation effect)
The solvent that adds methyl alcohol: chloroform=2.5ml: 1.25ml in the PBS solution that contains cell obtaining in recovery, vibrates 20 minutes, carries out centrifugal (3000rpm, 5 minutes) and separates, thereby obtain supernatant liquor a and precipitation b.Supernatant liquor a, for the quantitative analysis of ceramide/glucose ceramide, is used for precipitation b to the analysis of protein content.
(1) ceramide/glucose ceramide quantitative analysis
The solvent that adds PBS: chloroform=1.25ml: 1.25ml in the supernatant liquor a obtaining thus, vibrates 20 minutes, carries out centrifugal (3000rpm, 5 minutes) and separates, and obtains upper and lower two-phase.Reclaim lower phase, and be dried 40 minutes under 30 DEG C, nitrogen protection.In the dry product obtaining, add the chloroform of 100 μ l: the solvent of methyl alcohol=2ml: 1ml dissolves, and it is carried out to the parsing of the amount (be designated as respectively Cer and GlyCer, unit is μ g/ml) of ceramide and glucose ceramide by following thin plate chromatography (TLC) method.
By on ceramide (or glucose ceramide) standard substance and the extremely dry TLC plate of sample solution point, carry out thin plate chromatography taking CHCl3: CH3OH: CH3COOH (190: 9: 1v/v/v) as developing agent, treat that developing agent walks to thin plate top, dries up developing agent with blower; Repeat above step once.Then taking CHCl3: CH3OH: C3H6O (76: 20: 4v/v/v), as developing agent carries out thin plate chromatography, treats that developing agent walks to apart from 2.5cm place, thin plate bottom, stop exhibition layer, dry up with blower.Spray, with copper sulfate phosphoric acid solution, dries up, and chromatoplate is positioned over and in 180 DEG C of bake plate, toasts colour developing in 7 minutes.Scanning colour developing TLC plate also carries out ceramide (or glucose ceramide) analysis.
(2) analysis of protein content
For the ceramide/glucose ceramide amount in characterize cells, carry out protein content analysis.In above-mentioned precipitation b, add SDS (sodium laurylsulfonate) solution of 90 μ l and mix, at 60 DEG C, heat and within 2 hours, make protein denaturation degraded, after cooling, add therein the HCl solution of the 2N of 100 μ l, measure the wherein amount of protein (be designated as Pro, unit is μ g/ml) according to BCAKit (Protein quantitative analysis test kit) method.
(3) analytical results
For the sample of product of the present invention and reference substance, measure respectively Cer/Pro and GlyCer/Pro (seeing following formula).Taking the Cer/Pro of reference substance and GlyCer/Pro as 1, in table 1, represent the relative value of Cer/Pro and the GlyCer/Pro of product of the present invention.In addition, taking the amount of the protein in the every hole of reference substance as 100, obtain the relative value (Pro. (%)) of the amount of the protein in every hole of product of the present invention, and obtain accordingly the amount (with respect to the relative quantity of reference substance) of ceramide and the glucose ceramide in every hole,, Cer/Well=Cer/Pro × Pro. (%), GlyCer/Well=GlyCer/Pro × Pro. (%).In table 1, represent in the lump.
If Cer/Pro (or Cer/Well) is greater than 1 (value of reference substance), show that this sample has ceramide and produces facilitation effect; If GlyCer/Pro (or GlyCer/Well) is greater than 1 (value of reference substance), show that this sample has glucose ceramide and produces facilitation effect.
As shown in table 1, confirm that product A of the present invention, B have ceramide and produce facilitation effect and/or glucose ceramide generation facilitation effect.
Table 1
In addition, for sample A~B, do not joined and above-mentionedly directly carry out the quantitative analysis of ceramide/glucose ceramide containing (that is, not carrying out above-mentioned cell cultures) in 12 orifice plates of keratinocyte, operation is in addition same with above-described embodiment 1 to be carried out.Results verification in sample A~B itself, there is no ceramide or glucose ceramide.
Show thus, in product of the present invention itself, there is not ceramide or glucose ceramide, but product of the present invention have ceramide produces facilitation effect and/or glucose ceramide generation facilitation effect, can be used as ceramide and/or glucose ceramide production accelerant and uses.

Claims (12)

1. a manufacture method for ceramide and/or glucose ceramide production accelerant, wherein,
In the substratum that contains bean dregs and carbohydrate, cultivate the microorganism of Schizosaccharomyces (Schizosaccharomyces), in clear liquid, obtain from it ceramide production accelerant and/or glucose ceramide production accelerant,
The microorganism of described Schizosaccharomyces (Schizosaccharomyces) is eight spore fission yeasts (Schizosaccharomyces octoporus).
2. the manufacture method of ceramide as claimed in claim 1 and/or glucose ceramide production accelerant, wherein,
Described carbohydrate is glucose.
3. the manufacture method of ceramide as claimed in claim 2 and/or glucose ceramide production accelerant, wherein,
Described substratum is made up of bean dregs, glucose and water.
4. the manufacture method of ceramide as claimed in claim 3 and/or glucose ceramide production accelerant, wherein,
The content of bean dregs described in described substratum is 8~12w/v%, and the content of described carbohydrate is 0.8~1.2w/v%.
5. the manufacture method of ceramide as claimed in claim 1 and/or glucose ceramide production accelerant, wherein,
At 27~35 DEG C, carry out described cultivation.
6. the manufacture method of ceramide as claimed in claim 1 and/or glucose ceramide production accelerant, wherein,
Described incubation time is 1~7 day.
7. the manufacture method of ceramide as claimed in claim 1 and/or glucose ceramide production accelerant, wherein,
The culture obtaining by described cultivation is carried out centrifugal, thereby obtain described supernatant liquor.
8. the manufacture method of ceramide as claimed in claim 7 and/or glucose ceramide production accelerant, wherein,
In the described supernatant liquor of centrifugal rear acquisition, add after ethanol, set it as ceramide production accelerant and/or glucose ceramide production accelerant.
9. the manufacture method of ceramide as claimed in claim 8 and/or glucose ceramide production accelerant,
Wherein, further to described added the material obtaining after ethanol to refine by ultrasonication, centrifugation, filtration, vacuum drying treatment after, obtain ceramide and/or glucose ceramide production accelerant.
10. the fermented product extract of bean dregs is used for the purposes of the non-therapeutic purpose of the generation that promotes ceramide and/or glucose ceramide,
The fermented product extract of described bean dregs is in the substratum that contains bean dregs and carbohydrate, cultivate the microorganism of Schizosaccharomyces (Schizosaccharomyces) and in clear liquid, obtain from it,
The microorganism of described Schizosaccharomyces (Schizosaccharomyces) is eight spore fission yeasts (Schizosaccharomyces octoporus).
The fermented product extract of 11. bean dregs is as the purposes of the non-therapeutic purpose of ceramide production accelerant and/or glucose ceramide production accelerant,
The fermented product extract of described bean dregs is in the substratum that contains bean dregs and carbohydrate, cultivate the microorganism of Schizosaccharomyces (Schizosaccharomyces) and in clear liquid, obtain from it,
The microorganism of described Schizosaccharomyces (Schizosaccharomyces) is eight spore fission yeasts (Schizosaccharomyces octoporus).
The purposes of the fermented product extract of 12. bean dregs in manufacture ceramide production accelerant and/or glucose ceramide production accelerant,
The fermented product extract of described bean dregs is in the substratum that contains bean dregs and carbohydrate, cultivate the microorganism of Schizosaccharomyces (Schizosaccharomyces) and in clear liquid, obtain from it,
The microorganism of described Schizosaccharomyces (Schizosaccharomyces) is eight spore fission yeasts (Schizosaccharomyces octoporus).
CN201110289082.2A 2010-11-09 2011-09-15 Manufacturing method of ceramide production promoter Expired - Fee Related CN102994558B (en)

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CN201110289082.2A CN102994558B (en) 2011-09-15 2011-09-15 Manufacturing method of ceramide production promoter
JP2013522070A JP5639713B2 (en) 2010-11-09 2011-11-08 Method for producing ceramide and / or glucosylceramide production promoter
PCT/CN2011/001877 WO2012062043A1 (en) 2010-11-09 2011-11-08 Method for producing promoter from ceramide and/or glucosylceramide

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010013179A1 (en) * 2008-07-29 2010-02-04 L'oreal Cosmetic use of microorganisms for the treatment of oily skin
CN101653561A (en) * 2008-08-18 2010-02-24 复旦大学附属中山医院 Ceramide production accelerant
CN101653537A (en) * 2008-08-18 2010-02-24 复旦大学附属中山医院 Ceramide production accelerant

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10259135A (en) * 1997-01-17 1998-09-29 Kanebo Ltd Ceramide synthesis promoter
JPH11322534A (en) * 1998-05-14 1999-11-24 Kanebo Ltd Ceramide synthesis accelerator

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010013179A1 (en) * 2008-07-29 2010-02-04 L'oreal Cosmetic use of microorganisms for the treatment of oily skin
CN101653561A (en) * 2008-08-18 2010-02-24 复旦大学附属中山医院 Ceramide production accelerant
CN101653537A (en) * 2008-08-18 2010-02-24 复旦大学附属中山医院 Ceramide production accelerant

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