CN101622267B - Immunomodulator - Google Patents
Immunomodulator Download PDFInfo
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- CN101622267B CN101622267B CN2008800069122A CN200880006912A CN101622267B CN 101622267 B CN101622267 B CN 101622267B CN 2008800069122 A CN2008800069122 A CN 2008800069122A CN 200880006912 A CN200880006912 A CN 200880006912A CN 101622267 B CN101622267 B CN 101622267B
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
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- A—HUMAN NECESSITIES
- A21—BAKING; EDIBLE DOUGHS
- A21D—TREATMENT, e.g. PRESERVATION, OF FLOUR OR DOUGH, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS; PRESERVATION THEREOF
- A21D2/00—Treatment of flour or dough by adding materials thereto before or during baking
- A21D2/08—Treatment of flour or dough by adding materials thereto before or during baking by adding organic substances
- A21D2/14—Organic oxygen compounds
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- A—HUMAN NECESSITIES
- A21—BAKING; EDIBLE DOUGHS
- A21D—TREATMENT, e.g. PRESERVATION, OF FLOUR OR DOUGH, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS; PRESERVATION THEREOF
- A21D2/00—Treatment of flour or dough by adding materials thereto before or during baking
- A21D2/08—Treatment of flour or dough by adding materials thereto before or during baking by adding organic substances
- A21D2/14—Organic oxygen compounds
- A21D2/16—Fatty acid esters
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/20—Animal feeding-stuffs from material of animal origin
- A23K10/26—Animal feeding-stuffs from material of animal origin from waste material, e.g. feathers, bones or skin
- A23K10/28—Animal feeding-stuffs from material of animal origin from waste material, e.g. feathers, bones or skin from waste dairy products
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/158—Fatty acids; Fats; Products containing oils or fats
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P60/00—Technologies relating to agriculture, livestock or agroalimentary industries
- Y02P60/80—Food processing, e.g. use of renewable energies or variable speed drives in handling, conveying or stacking
- Y02P60/87—Re-use of by-products of food processing for fodder production
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The object is to find a novel mechanism of action of ganglioside GD3 on an immune function and a use application of ganglioside GD3 for medical purposes utilizing the mechanism, and to provide a pharmaceutical agent which is effective for use as a prophylactic or therapeutic agent for an immune disease and a food/beverage and a feed each comprising the pharmaceutical agent. Thus, disclosed is an immunomodulating agent comprising ganglioside GD3 as an active ingredient. The ganglioside DG3 is preferably derived from milk. The immunomodulating agent can be used in a food/beverage or a feed.
Description
Technical field
The present invention relates to Ganglioside, GD3 as the immune function controlling agents of effective constituent and the drink food and feed that contains this conditioning agent.
Background technology
Sphingolipids,sialo are the general name that comprises the glycolipid matter of sialic acid, and are known in organism, contain a large amount of Sphingolipids,sialo in brain and the red blood corpuscle.And the known Sphingolipids,sialo that also contain in various food contain a large amount of Sphingolipids,sialo in the esp milk.In addition, with regard to Sphingolipids,sialo, reported the inhibition of various viruses or toxicity bacterium active, to because the result for the treatment of of the disordered brain function that cerebral ischemia or Parkinson's disease cause, the differentiation promoter action of monocyte or macrophage system cell, the various physiological actions such as the Function Regulation of epithelial growth factor receptor.Mainly contain these two kinds of Sphingolipids,sialo of GD3 and GM3 in the milk, when the Sphingolipids,sialo in these milk sources of oral administration, reported that also it has the raising learning capacity, improves (patent documentation 1-3) such as effects that the oral cavity bacterium group acts on, prevents coli-infection.And, Sphingolipids,sialo are disclosed, especially GM3, make mucomembranous cell maturing (patent documentation 4) between baby's intestines, disclose because maturing, prevent the anaphylactogen material by the gap between the mucomembranous epithelial cell, by on mucous membrane, being combined with anaphylactogen, the generation of the IgA that prevents its intrusion is increased.
Known cytokine mainly is the protein properties factor that immune system cell produces, and it not only has rich and varied physiological action to immune system cell but also to a lot of cells.In the cytokine, TNF-α is in organism defence, the representative cytokine of the struvite cytokine that plays a major role in the inflammatory reaction etc.Can expect that the influential factor of generation ability for TNF-α has the biophylaxis ability and regulates the effect of inflammatory reaction.And known disturbances element γ (IFN-γ) is the representative cytokine of control cellular immunity, promotes the T cell of Th0 type to break up to the Th1 type.In addition, it is believed that IL-4 is the representative cytokine of control volume fluidity immunity, promote the propagation of Th2 cell.Therefore, by analyzing the variation that IFN-γ and IL-4 produce ability in the immune tissue, the T cell that can infer existence is that to be in the Th1 type dominant, namely is cellular immunity in dominant situation? still being in the Th2 type dominant, i.e. is body fluid type immunity in dominant situation?
Patent documentation 1: Unexamined Patent 11-246418 communique
Patent documentation 2: JP 2005-320275 communique
Patent documentation 3: JP 2001-2704 communique
Patent documentation 4: Unexamined Patent 8-109133 communique
Summary of the invention
The problem that invention will solve
The medicinal use that problem of the present invention is to find a kind of new role mechanism relevant with immunologic function of Ganglioside, GD3 and utilizes this mechanism is provided as the effective medicine of preventive of various Immunological diseases and the drink food and feed that contains this medicine.
Solve the method for problem
The inventor carries out various researchs with regard to Ganglioside, GD3 to the function of cytokine in order to solve above-mentioned problem, found that Ganglioside, GD3 suppresses the generation of TNF-α, IFN-γ, and promotes the generation of IL-4, has finished the present invention based on this understanding.
That is, the present invention is with the immune function controlling agents of Ganglioside, GD3 as effective constituent.The present invention is characterised in that still described Ganglioside, GD3 derives from the aforementioned immune function controlling agents of milk.The present invention still contains the drink food and feed of aforementioned immune function controlling agents.
The invention effect
The immune function controlling agents of the application of the invention uses Ganglioside, GD3 to suppress the generation of TNF-α, IFN-γ, and promotes the generation of IL-4, can regulate immunologic function.Immune function controlling agents of the present invention can be used for the diseases relevant with immunologic function such as food for preventing anaphylaxis or atopic dermatitis.
Description of drawings
Fig. 1 is the result's of expression test example 1 figure.
Fig. 2 is the result's of expression test example 2 figure.
Fig. 3 is the result's of expression test example 2 figure.
Embodiment
Below just the present invention be elaborated.
The Ganglioside, GD3 that uses as effective constituent among the present invention obtains with any means can.That is, the Ganglioside, GD3 by the separation and purification from the brain of livestock etc. of existing method can be used, and the Ganglioside, GD3 of method (the JP 63-269992 communique) acquisition that utilizes efficient recovery from milk can be used.According to producing in a large number Ganglioside, GD3 with technical scale with the method for putting down in writing in the piece of writing communique.And, with a piece of writing put down in writing in the communique from milk the separation and Extraction Ganglioside, GD3 method as a reference, it thes contents are as follows.Namely, by making the protein decomposition enzymes such as the acid such as hydrochloric acid or lactic acid or trypsinase, stomach en-act on the milk materials such as milk, buttermilk, whey, skimmed milk, decomposing protein, process the protein decomposing solution that obtains by ultrafiltration process, gel infiltration method or dialysis method, concentrated Sphingolipids,sialo are prepared.Like this preparation Sphingolipids,sialo consisted of by GM3 and GD3, among the present invention with Ganglioside, GD3 as effective constituent.
Immune function controlling agents of the present invention contains Ganglioside, GD3 as effective constituent, can be used as the preparation with various formulations and uses, and formulation is not particularly limited.Therefore the effective constituent Ganglioside, GD3 can use with various vehicle or carrier etc., can be engaged in the preparation of the various formulations such as tablet, capsule, pulvis, liquid preparation.In addition, immune function controlling agents of the present invention also can comprise having the other medicines of regulating immunity function.And the kind of diet product of the present invention also is not particularly limited, and may be combined in milk, processing milk, milk beverage, sour milk, refreshment drink water, coffee drinks, fruit juice, jelly, prestige China biscuit, biscuit, bread, noodles, diet product or the nutritive food such as sausage, and nutritional supplementation composition.In addition, feed kind of the present invention is not particularly limited.Be explained, immune function controlling agents of the present invention, the drink food and feed can prepare except containing Ganglioside, GD3 according to a conventional method.
Among the present invention, in order to make it to bring into play the immunologic function regulating effect, the combined amount of Ganglioside, GD3 in medicine, diet product or feed etc. can be adjusted to can be by about average every day of general picked-up 0.1-5mg.And with Ganglioside, GD3 during as effective constituent, the administration object does not limit, when being used for enough better effects if during the people of maturation of digestive tube.
Embodiment
Below, the present invention will be described in more detail by embodiment and test example.In embodiment and test example, " % " just means " % by weight " unless otherwise specified.
(embodiment 1)
(preparation of Ganglioside, GD3)
Add 1% protease in the whey of when making cheese, discharging to 1.5kL, under pH8.0,55 ℃, carry out 2 hours enzyme reaction, thus the protein in the hydrolyzed whey.With this reaction solution by ultra-filtration membrane (Cefilt 10kDaNG: Off イ Le テ Star Network society system) process and to remove protein hydrolystate and lactose, be concentrated to 30% concentration with vaporizer after, lyophilize has obtained the powder that 1.5kg contains Sphingolipids,sialo.Be explained, this Sphingolipids,sialo amount that contains in the Sphingolipids,sialo powder is approximately 1%.Then, with anionite-exchange resin Dowex-1 (acetic acid type: DowChemical company system) be filled in the post (diameter 10cm * high 100cm), use by chloroform: methyl alcohol: behind the solution equilibria that water (60: 30: 8) consists of, allow and be suspended in 30L by chloroform by the above-mentioned Sphingolipids,sialo powder that contains: methyl alcohol: the suspension that the solution that water (60: 30: 8) consists of is made passes through, after making the acidic substance such as Sphingolipids,sialo be adsorbed on the post, with 20L by chloroform: methyl alcohol: the solution washing post that water (60: 30: 8) consists of, with 20L contain the 2M sodium-acetate by chloroform: methyl alcohol: the eluant solution that water (60: 30: 8) consists of, reclaim the elutriant that contains Sphingolipids,sialo.After this elutriant desolventizing that contains Sphingolipids,sialo of drying under reduced pressure, add the 1N sodium hydroxide solution, by carrying out 2 hours reaction decomposes phosphatide in 40 ℃.Then (Cefilt 10kDaNG: Off イ Le テ Star Network society system) desalination and concentration is carried out in processing with ultra-filtration membrane with this reaction solution, after the lyophilize, with 200mL by chloroform: the solution dissolving that methyl alcohol (85: 15) consists of, by silicagel column (diameter 5cm * high 40cm), Sphingolipids,sialo are adsorbed on the silica gel again.Then, use chloroform: methanol solution gradient elution Sphingolipids,sialo, concentrated and lyophilize has obtained 15.2g Ganglioside, GD3 powder.Be explained, the purity of this Ganglioside, GD3 is analyzed by high performance liquid chromatography, consequently more than 97%.
Test example below is shown, and the present invention will be described in more detail.In test example, all use the Balb/C male mice.And Ganglioside, GD3 uses the Ganglioside, GD3 powder dissolution that embodiment 1 is obtained by the concentration of 10 μ g/ml in the RPMI1640 substratum that has added 10% foetal calf serum, the micelle that forms by 30 minutes ultrasonication.
[test example 1]
(Ganglioside, GD3 produces the impact of ability on the TNF-α of Macrophage in Spleen)
Put to death large Balb/C male mice in 10 ages in week, collect spleen.In culture dish, spleen is chopped up, with the fine extruding of injection tube, by sieving separating Morr. cell.In the substratum (10%FCS/RPMI1640) that in the RPMI1640 substratum, has added foetal calf serum by final concentration 10% and obtained the spleen cell cultures of separating after 2 hours, with same medium washing 2 times, is separated the scavenger cell of adhesion.Add to the Macrophage in Spleen that separates and to have added the 10%FCS/RPMI1640 substratum of Ganglioside, GD3 of embodiment 1 that final concentration is 10 μ g/ml or what all not have a RPMI1640 substratum (contrast) of interpolation, cultivated 2 hours.Then press final concentration 1 μ g/ml and add LPS, cultivated again 3 hours.After cultivating termination, collect substratum, use simultaneously 0.1%SDS solution with cell solution.By the TNF-α concentration in the collected substratum of the biological test method mensuration that adopts the L929 l cell.With the intracellular DNA amount of the fluorescence spectrophotometry solubility of passing through DAPI, obtain the TNF-α secretory volume of per unit DNA amount.The results are shown in Fig. 1.
Consequently, in the Ganglioside, GD3 interpolation group, compare with contrast (without adding) group, TNF-α produces ability and significantly descends.By in substratum, directly adding Ganglioside, GD3, TNF-α generation ability is suppressed, this enlightenment Ganglioside, GD3 has anti-inflammatory action.
[test example 2]
(Ganglioside, GD3 produces the impact of ability on the IL-4 that depends on splenocyte and IFN-γ)
Similarly carry out separating of cell with test example 1.That is, after the spleen of collection and test example 1 the same the chopping up, after firmly extruding makes it to break into pieces, by the sieving separating cell.Cell is seeded in the 10%FCS/RPMI1640 substratum or added by final concentration 10 μ g/ml in the 10%FCS/RPMI1640 substratum of Ganglioside, GD3 of embodiment 1.Cultivate beginning and press final concentration 5 μ g/ml interpolation in the time of the 2nd day as the concanavalin A of mitogen, cultivated again 3 days.After cultivating end, dissolved cell when reclaiming substratum.IL-4 in the substratum, IFN-γ concentration is measured with sandwich ELISA method respectively.Measure the DNA concentration in the cell, obtain the cytokine secretion amount of per unit DNA amount.The results are shown in Fig. 2,3.
Such as Fig. 2, shown in 3, in the splenocyte, the tendency that IL-4 generation ability increases appears, and IFN-γ produces ability significantly to be reduced.These result's enlightenments are by adding Ganglioside, GD3, and the Th1 that has brought out in the spleen suppresses.If observe the Th1/Th2 balance in the body, can say that then the initial stage in anaphylactic diseases such as food allergy reaction or atopical dermatitis has reached the dominant state of Th1.Therefore can think the carrying out that can suppress anaphylactic disease by suppressing Th1, namely effective to the Ammonium Glycyrrhizate disease.In this test example, Ganglioside, GD3 demonstrates Th1 type restraining effect, this enlightenment is by daily picked-up Ganglioside, GD3, Th1 type in the immunity system of organism is that cellular immunity is induced to suppressing direction, this shows because Ganglioside, GD3 suppresses the initial stage of anaphylaxis morbidity, therefore can be used as the food materials of the effect with Ammonium Glycyrrhizate reaction.
(embodiment 2)
(containing the preparation of the powder of Ganglioside, GD3)
Add the 0.5kg subtilisin in the solution that 180L water makes to the 20kg buttermilk powder is dissolved in, in pH7.6,40 ℃ of reactions of temperature 15 hours, behind the decomposing protein, in 90 ℃ of heat-sterilizations 10 minutes, make enzyme deactivation.Then, with to be equipped with membrane area be the ultra-filtration membrane device (LAB-20 type Module:DDS company system) of 0.36 square metre filter membrane, with 40 ℃ of temperature, flow 15L/ divide, square pressure 0.6MPa filters mentioned solution, concentrated Sphingolipids,sialo.This solution is carried out lyophilize, obtain to contain the powder 1kg that contains Ganglioside, GD3 of the 7.5g Ganglioside, GD3 of having an appointment.The powder that contains Ganglioside, GD3 that obtains like this can directly use as immunomodulator of the present invention.
(embodiment 3)
(using the preparation of the milk powder of Ganglioside, GD3)
The powder 200g that contains Ganglioside, GD3 of preparation among the embodiment 2 is dissolved in the 700kg water with VITAMIN and the mineral composition of 6.8kg casein, 70.0kg whey powder, 1kg.Remix 23.0kg Vegetable oil lipoprotein after homogenizing, through sterilization, concentrated and drying process, has obtained the milk powder that 100kg contains immune function controlling agents of the present invention.The content of the Ganglioside, GD3 in the 100g milk powder that obtains is about 1.0mg.
(embodiment 4)
(containing the preparation of the healthy beverage of Ganglioside, GD3)
Use the powder that contains Ganglioside, GD3 of preparation among the embodiment 2, prepare the healthy beverage of immune function controlling agents of the present invention according to the proportioning of table 1.The composition of table 1 is dissolved in the water makes 5L.With pressure 160kg/cm
2After this solution homogenized, keep carrying out sterilization in 3 seconds in 120 ℃ with board-like sterilization Machine, then be cooled to 5 ℃.The healthy beverage that obtains is filled in the paper container of capacity 200m l.The every 100ml of this healthy beverage approximately contains the GD3 of 2.4mg.
Table 1
(embodiment 5)
(use contains the preparation of tablet of the powder of Ganglioside, GD3)
Be filled in the soft capsule that is consisted of by gelatin by every 100mg according to the Sphingolipids,sialo powder of ordinary method with preparation among the embodiment 1, obtain immune function controlling agents of the present invention (tablet).
Industrial applicability
Of the present invention take Ganglioside, GD3 as effective constituent immune function controlling agents cooperate the diet product of this conditioning agent or the prevention of the feed pair various diseases relevant with immunologic function useful.
Claims (4)
1. Ganglioside, GD3 produces purposes in the promotor at preparation IL-4.
2. purposes claimed in claim 1 is characterized in that, described Ganglioside, GD3 derives from milk.
3. Ganglioside, GD3 produces the purposes that promotes in the diet product at preparation IL-4.
4. Ganglioside, GD3 produces the purposes that promotes in the feed at preparation IL-4.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007052519A JP2008214241A (en) | 2007-03-02 | 2007-03-02 | Immunomodulator |
| JP052519/2007 | 2007-03-02 | ||
| PCT/JP2008/053489 WO2008108262A1 (en) | 2007-03-02 | 2008-02-28 | Immunomodulating agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101622267A CN101622267A (en) | 2010-01-06 |
| CN101622267B true CN101622267B (en) | 2013-01-30 |
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ID=39738145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008800069122A Expired - Fee Related CN101622267B (en) | 2007-03-02 | 2008-02-28 | Immunomodulator |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2008214241A (en) |
| KR (1) | KR20090115860A (en) |
| CN (1) | CN101622267B (en) |
| WO (1) | WO2008108262A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6282446B2 (en) * | 2013-11-14 | 2018-02-21 | 雪印メグミルク株式会社 | Bacteriostatic or antibacterial agent and method for producing the same |
| US10849926B2 (en) | 2015-11-30 | 2020-12-01 | The Noguchi Institute | GM3-promoted inflammation inhibitor and inflammatory cytokine production inhibitor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020122795A1 (en) * | 2000-12-08 | 2002-09-05 | Paller Amy S. | Compositions containing gangliosides for use in the treatment of skin disorders |
| EP0777486B1 (en) * | 1994-08-24 | 2003-04-16 | N.V. Nutricia | Allergy-protective formula food with gangliosides |
| US6814981B1 (en) * | 1997-06-12 | 2004-11-09 | Csl Limited | Ganglioside immunostimulating complexes and uses thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4965063B2 (en) * | 2004-05-07 | 2012-07-04 | 雪印メグミルク株式会社 | Oral flora improving agent, antibacterial agent and growth promoter. |
| JP2007131550A (en) * | 2005-11-08 | 2007-05-31 | Snow Brand Milk Prod Co Ltd | Immunity function regulator |
-
2007
- 2007-03-02 JP JP2007052519A patent/JP2008214241A/en active Pending
-
2008
- 2008-02-28 WO PCT/JP2008/053489 patent/WO2008108262A1/en active Application Filing
- 2008-02-28 CN CN2008800069122A patent/CN101622267B/en not_active Expired - Fee Related
- 2008-02-28 KR KR1020097018241A patent/KR20090115860A/en not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0777486B1 (en) * | 1994-08-24 | 2003-04-16 | N.V. Nutricia | Allergy-protective formula food with gangliosides |
| US6814981B1 (en) * | 1997-06-12 | 2004-11-09 | Csl Limited | Ganglioside immunostimulating complexes and uses thereof |
| US20020122795A1 (en) * | 2000-12-08 | 2002-09-05 | Paller Amy S. | Compositions containing gangliosides for use in the treatment of skin disorders |
Non-Patent Citations (2)
| Title |
|---|
| Dozmorov，I.M. et al..nanomolar concentrations of gangliosids stimulate primary humoral response.《biochemistry and molecular biology international》.1997,第42卷(第1期),57－63. * |
| HOON,DAVE S.et al..gangliosides from human melanoma immunomodulate response of t cells to interleukin 2.《cellular immunology》.1988,第111卷(第2期),410-419. * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008108262A1 (en) | 2008-09-12 |
| JP2008214241A (en) | 2008-09-18 |
| KR20090115860A (en) | 2009-11-09 |
| CN101622267A (en) | 2010-01-06 |
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