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WO2001051079A1 - Inhibiteurs de production d'anticorps ige specifique d'un antigene - Google Patents

Inhibiteurs de production d'anticorps ige specifique d'un antigene Download PDF

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Publication number
WO2001051079A1
WO2001051079A1 PCT/JP2001/000161 JP0100161W WO0151079A1 WO 2001051079 A1 WO2001051079 A1 WO 2001051079A1 JP 0100161 W JP0100161 W JP 0100161W WO 0151079 A1 WO0151079 A1 WO 0151079A1
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WO
WIPO (PCT)
Prior art keywords
hydrolyzate
ceramides
lactoferrin
production
including humans
Prior art date
Application number
PCT/JP2001/000161
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English (en)
Japanese (ja)
Inventor
Takeshi Takahashi
Shinya Nagabuchi
Yoshitaka Nakamura
Takaji Yajima
Tamotsu Kuwata
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Meiji Dairies Corporation
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Filing date
Publication date
Application filed by Meiji Dairies Corporation filed Critical Meiji Dairies Corporation
Priority to JP2001551502A priority Critical patent/JP4787445B2/ja
Priority to AU25515/01A priority patent/AU782539B2/en
Priority to NZ519957A priority patent/NZ519957A/en
Publication of WO2001051079A1 publication Critical patent/WO2001051079A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • A61P37/04—Immunostimulants
    • 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
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an IgE antibody production inhibitor that is effective for preventing or improving allergic diseases such as atopic dermatitis.
  • the present invention also relates to a composition that stimulates the immune system in a living body to activate immunity. Skill
  • Lactoferrin is an iron-binding glycoprotein found in milk, but also in exocrine fluids such as saliva, tears, bile, and fluid, and is released by activated neutrophils at the site of inflammation You.
  • LF has a broad spectrum of biological activities. For example, it has an antibacterial effect, an antiviral effect, an antitumor effect, an inhibitory effect on cancer metastasis formation, and the like.
  • LF also affects cytoin secretion. For example, it promotes the secretion of human neutrophils from inulin-leukin-8 (IL-8), regulates the secretion of IL-1, IL-6, and TNFa, and suppresses the expression of GM-CSF at the gene level. is there.
  • IL-8 inulin-leukin-8
  • TNFa TNFa
  • cytokins plays a protective or etiological role in various disease states.
  • IgE IgE antibodies
  • influenza IFN-r influenza IFN-r
  • the production is controlled by a system centered on).
  • the production of IFN- ⁇ is induced by the higher IL-12 and IL-18.
  • IFN- ⁇ also has antiviral, antimicrobial, and antitumor activities due to various immunomodulatory functions (J. Immunol., 130: 2011-2013, 1983; Proc.
  • an object of the present invention is to find a new biological activity of LF, and to provide a drug or a functional food containing LF as an active ingredient based on the activity. Another object is to find an orally ingestible substance having an effect of enhancing the biological activity of LF when combined with LF. Disclosure of the invention
  • the present inventors found that immunization of mice that orally ingested LF, heat-treated LF, or LF hydrolyzate with ovalbumin (OVA), a major food allergen, suppressed the production of OVA-specific IgE antibodies. And that the production of antigen-specific IL-4 in the spleen cell culture system was suppressed. In addition, they found that culturing macrophages in the presence of LF enhanced IL-12 production by macrophages. Furthermore, it was found that IFN-r production in spleen cell culture system was markedly enhanced when LF and ceramides were used in combination.
  • OVA ovalbumin
  • Suppression of production of antigen-specific IgE antibodies by oral ingestion of LF is due to suppression of activation of IgE antibody-producing B lymphocytes by suppression of IL-4 production and to Thl dominance of Thl / Th2 balance by enhancement of IL-12 production. Probably due to the shift.
  • oral ingestion of LF can prevent a decrease in cellular immunity due to a shift toward Th2 immunity, and can prevent or improve allergic diseases and antibody-mediated nephritis.
  • the remarkable enhancement of IFN-production by the combination of LF and ceramides indicates that the combination of LF and ceramides is effective against viral diseases, bacterial infections, or tumors. Understand. That is, the present invention provides an inhibitor of IgE antibody production in mammals, including humans, containing LF or a hydrolyzate thereof as an active ingredient.
  • the present invention also provides a composition containing LF or a hydrolyzate thereof as an active ingredient, for suppressing IgE antibody production in mammals including humans and regulating immunity.
  • the present invention relates to a composition for enhancing IFN- ⁇ production of mammals including humans comprising LF or a hydrolyzate thereof and ceramides, an antiviral composition, an antibacterial infection composition, and an antitumor agent. It provides a composition.
  • the present invention also provides an immunostimulator composition for mammals, including humans, containing LF or a hydrolyzate thereof and ceramides.
  • the present invention also provides use of LF or a hydrolyzate thereof for producing an IgE antibody production inhibitor in mammals including humans.
  • the present invention also provides use of LF or a hydrolyzate thereof for producing a composition for suppressing immunity by suppressing the production of IgE antibodies in mammals including humans.
  • the present invention relates to a composition for enhancing IFN- ⁇ production in mammals including humans, an antiviral composition, an antibacterial infection composition, and an antitumor composition of LF or a hydrolyzate thereof and ceramides. Provide use for manufacturing.
  • the present invention also provides use of LF or a hydrolyzate thereof and ceramides for producing an immunostimulant composition for mammals including humans.
  • the present invention also provides a method for suppressing the production of IgE antibodies in mammals including humans, which comprises administering an effective amount of LF or a hydrolyzate thereof.
  • the present invention also provides a method for regulating immunity by suppressing the production of IgE antibodies in mammals including humans, which comprises administering an effective amount of LF or a hydrolyzate thereof.
  • the present invention administers an effective amount of LF or a hydrolyzate thereof and ceramides. It is intended to provide a method for enhancing IFN- ⁇ production in mammals including humans, or a method for treating a viral disease, bacterial infection or tumor.
  • the present invention provides a method for immunostimulating mammals including humans, which comprises administering an effective amount of LF or a hydrolyzate thereof and ceramides.
  • FIG. 2 is a graph showing the OVA-specific IgE antibody titer in serum (mean value SD; * p ⁇ 0.05) in the above.
  • FIG. 3 is a diagram showing the IL-4 producing ability of spleen cells in the same as above (cells were pooled in each group). Hata: ⁇ ⁇ ⁇ LF oral intake group, Painting: control group.
  • FIG. 5 is a diagram showing an OVA-specific IgE antibody titer in serum as in the above. (* P less 0.05)
  • FIG. 7 is a diagram showing 0VA-specific IL-4 production of splenocytes in the above. Cp ⁇ 0.05
  • FIG. 9 is a diagram showing OVA-specific IL-4 production of splenocytes in the above.
  • Control group 7, 2.23 ⁇ 4bLF; 8)
  • FIG. (* p ⁇ 0.05)
  • FIG. 11 is a diagram showing the effect on serum OVA-specific IgE antibody titers in the above.
  • FIG. 12 is a diagram showing OVA-specific IFN- ⁇ production of spleen cells in the above.
  • FIG. 13 is a diagram showing OVA-specific IL-4 production of splenocytes in the above.
  • FIG. 14 is a diagram showing IL-12 production in the culture supernatant after culturing mouse peritoneal macrophages in the presence of 100 ⁇ g / ml of mouse LF. ("P x 0.01")
  • FIG. 15 shows cultures of splenocytes of mice after intraperitoneal administration of lactosylceramide or splenocytes after non-administration of lactosylceramide in the presence or absence of 100 xg / ml LF.
  • FIG. 4 is a view showing IFN- ⁇ production in a supernatant.
  • Th cells Cytokines produced by CD4 + helper T cells (Th cells) play an important role in IgE production. Th cells are roughly divided into two subpopulations, Th1 cells involved in cell-mediated immunity and Th2 cells involved in humoral immunity, depending on the difference in cytodynamic force produced and their function. Involved are Th2 cells (J. Immunol., 136: 2348, 1986).
  • Th1 cells and Th2 cells are in a relationship of mutually inhibiting their differentiation and function expression by the cytokines produced respectively. That is, Th2 cells have IL-4, IL-5, And produce IL-6 to positively regulate IgE production. Conversely, IFN-r produced by Thl cells suppresses IgE production by suppressing the IgE class switch and Th2 cell response. For this reason, IgE production and allergic diseases are characterized by enhanced Th2 cell responses (Nature, 383: 787, 1996). Therefore, it can be prevented or improved by inducing a Thl cell response to restore the Thl / Th2 balance to normal. Attempts have therefore been made to search for factors that are likely to induce a Thl response from food components.
  • IL-12 is a cytokine produced by antigen-presenting cells such as monocytes, macrophages, and dendritic cells, and plays an important role in the production of IFN- ⁇ and inducing the differentiation of helper T cells to Thl (Blood , 84: 4008, 1994; J. Leukoc. Biol., 55: 280, 1994). Gazzinelli et al. (J. Immunol., 153: 2533, 1994) reported that when mice were infected with Toxoplasma gondii, IL-12 production in spleen and peritoneal cells was increased, and the mice were further exposed to anti-IL-12 antibodies.
  • antigen-presenting cells such as monocytes, macrophages, and dendritic cells
  • atopic dermatitis which was previously thought to be mild dermatitis, is now counted as one of the intractable diseases seen from infants to adults, and has become a major social problem.
  • One of the causes is suspected of abnormal metabolism of sphingolipids in the epidermis.
  • Ceramides have also begun to be used as beauty foods. Therefore, the present inventors considered that oral ingestion of a combination of LF and ceramides would further enhance the effect of LF alone in preventing and improving allergic diseases. Therefore, the effect of the combination of LF and ceramides on IFN- ⁇ production was examined.
  • Allergic inflammatory diseases include, for example, chronic bronchial asthma, atopic dermatitis, hay fever (allergic rhinitis), allergic vasculitis, allergic conjunctivitis, allergic gastroenteritis, allergic liver disorder, allergic cystitis And allergic purpura. Alternatively, it can be expected to prevent or improve nephritis and the like mediated by antibodies.
  • IFN- ⁇ production is markedly enhanced.Thus, by using LF and ceramides in combination, the Thl / Th2 balance is shifted to the Thl superiority. It can be seen that the production of IgE antibody is suppressed.
  • IFN-a has antiviral, antitumor, cytotoxic T lymphocyte, natural killer cell (NK cell) activity, neutrophil activation, macrophage activation, MHC class II expression promotion effect, IL-2 receptor expression promotion effect, It is known that the expression of Fc receptor is promoted. Also, IFN is a biological substance that originally plays a part in the defense mechanism against foreign substances in living organisms, has extremely high selective toxicity, and is highly safe for living organisms.
  • a composition combining LF and ceramides can be an antiviral agent, an antitumor agent, and an antimicrobial agent.
  • LF no abnormalities were observed in the acute toxicity test and the subacute toxicity test of LF in rats using the maximum dose of 2,000 mg / kg / body weight / day. Is not recognized (Milk Science Vol.48, No.3, P227-232, 1999).
  • LD 5D Oryza Ceramide to mouse is 5, 000mg / kg or more (FOOD Style Vol.4, No.10: 99-105 , 2000).
  • the LF that can be used in the present invention includes, for example, commercially available LF, colostrum of mammals (eg, humans, pests, higgs, goats, pests, etc.), transitional milk, normal milk, terminal milk, and the like, or LF separated from these skim milks derived from milk, whey, etc. by conventional methods (for example, ion-exchange chromatography), hydrolysates with acids or enzymes, and apoproteins deferred with hydrochloric acid, citric acid, etc.
  • metal-saturated or partially-saturated LF which is obtained by chelating LF and apo LF with metals such as iron, copper, zinc, and manganese.
  • a known hydrolysis means can be used for preparing the LF hydrolyzate of the present invention.
  • trypsin is used in the present invention as an enzyme, but other enzymes such as pepsin and papain are also used, but are not limited to these enzymes as long as the hydrolyzate has the activity of the present invention.
  • the hydrolyzate may be fractionated by a conventional method such as ultrafiltration and then subjected to a concentration operation. The obtained liquid hydrolyzate may be used as it is or may be lyophilized before use.
  • Recombinant LF includes a polypeptide having substantially the same amino acid sequence as described by Orla III. Conneely et al.
  • Recombinant LF also includes recombinant LF expressed in transgenic animals, e.g., pests, wherein the glycosylation pattern may differ from that of native LF obtained from human milk. .
  • the ceramides used in the present invention contain ceramide-related substances, and for example, sphingo lipids, particularly glycolipids, are preferred.
  • Glycosphingolipids include, for example, the simplest glycosphingolipids are cerebrosides found in milk, brain, and kidneys, as well as sulfatide with a sulfate group, ceramide oligohexoside with a few neutral sugars, and amino. Examples include globosides with sugars and gandariosides with sialic acid.
  • the structure of the glycosphingolipid is different from that of the glycosphingolipid, and the structure of the glycosphingolipid is more than 100 types, but all those having the action of the present invention are included.
  • lactosylceramide Preference is given to lactosylceramide, galactosylceramide, darcosylceramide and the like. Also preferred is sufingomyelin, which is a type of phospholipid (contained in milk).
  • sufingomyelin which is a type of phospholipid (contained in milk).
  • Ceramide 2 and Cosmo Farm's Ceramide 3 are such. In the present invention, these ceramides can also be used as long as they have the action of the present invention.
  • plant-derived ceramides are receiving attention and are starting to be used.
  • rice-based sphingolipids like animal sphingolipids, have a basic skeleton of hydrophobic ceramide, which is a long-chain base sphingosine with an acid amide bond to a fatty acid.
  • sphingolipids derived from rice vary in species depending on the difference in carbon number of the long-chain base sphingosine and fatty acids, and the presence or absence of hydroxyl groups and double bonds. According to a report by Prof. Fujino of Obihiro University of Agriculture, there are at least more than 20 species of sphingolipid molecular species.
  • the present invention also includes these ceramides.
  • LF all LFs and LFs having the same Of ceramides, preferably 0.00001-0.1% by weight, more preferably 0.00005-0.01% by weight, based on the total weight of the composition.
  • LF is estimated to be preferably 0.005 to 10% by weight, particularly preferably 0.01 to 5% by weight, most preferably 0.01 to 3% by weight, based on the total weight of the composition.
  • those skilled in the art will be able to easily determine the optimal amount according to the composition to be used as a control, for example, by experiments described below.
  • the ceramide content in breast milk is known, and it is considered to be a tentative standard in the amount of ceramides to be mixed.
  • the present invention has revealed that oral ingestion of LF suppresses antigen-specific IgE antibody production. Therefore, a person skilled in the art selects a preferred form of LF and an effective amount applicable to the present invention from the above-mentioned various LFs based on the present invention, for example, using IgE antibody production as an index, and selects clinical data, Alternatively, taking into account the relationship between clinical symptoms and serum IgE in patients, foods, dietary supplements, foods for the sick, infant formulas, health foods, health claims foods, functional foods, foods for specified health use, Alternatively, it is possible to determine the shape and effective dose of the LF when used for pharmaceuticals and the like. Therefore, the type of LF thus determined and its effective dose are encompassed by the present invention.
  • the technology of adding and processing LF to foods and the like is well known and used. When an effective amount of LF is used as a pharmaceutical, it can be processed into various formulations known to those skilled in the art. Example
  • test examples 1 to 4 and 6 used 3-week-old male BALB / c mice (Japan SLC; Shizuoka, Japan), and test example 5 used 8-week-old female BALB / c mice. (Japan SLC; Shizuoka, Japan) was used. Test for significant difference between control group and experimental group Performed by Student 'st test.
  • the control group (n 8) had free access to the above diet and water without bLF.
  • Test Example 3 Heat-treated bLF inhibits IgE antibody and cytokine production
  • the diet [bLF (+)] obtained by adding 2.2 bLF to the diet of Test Example 1 was heated at 70 ° C for 1 hour.
  • a diet without bLF [bLF (-)] was similarly heated at 70 ° C for 1 hour.
  • mice were allowed free access to bLF (+) (experimental group) or bLF (—) (control group) during the experimental period.
  • mice On days 5, 14, 23 and 33 after the start of the experiment, mice were immunized intraperitoneally with 10 g of ovalbumin (0VA, manufactured by Seikagaku Corporation) together with 4 mg of aluminum hydroxide.
  • Day 8 Day 30 after the third intraperitoneal immunization (7 weeks Aged), blood was collected from the tail, and antibodies in the serum were measured by ELISA.
  • Splenocytes were collected individually on day 11 (day 33) after the third peritoneal immunization and day 8 (day 40) after the fourth peritoneal immunization.
  • Splenocytes were treated with 10% FCS, lOOU / ml penicillin G, 100 xg / ml streptomycin and 5X10- 2-mercaptoethanol for 72 hours with various concentrations of OVA (0, 50, 100, 200 and 400 ii / ml).
  • the cells were cultured in RPMI 1640 medium. After culturing, the levels of IFN- ⁇ and IL-4 in the culture supernatant were measured by ELISA.
  • spleen cells produced IFN- ⁇ at each concentration of OVA (0, 50, 100, 200, and 400 ⁇ g / ml), as in the three immunizations, in both groups. Almost no difference was found between them (Fig. 8).
  • IL-4 production at 0 VA at each of the above concentrations was significantly significantly lower in the experimental group than in the control group (FIG. 9).
  • heating bLF does not lose its antigen-specific IgE antibody production inhibitory action and IL-4 production inhibitory action.
  • Trypsin (Wako Pure Chemical Industries, Ltd., 207-09891, for biochemistry, manufactured by pig kidney, 4500 USP trypsin units / mg) was dissolved in sterile PBS to give a trypsin stock solution (X500, 50 mg / ml). 10 g of b LF (Wako Pure Chemical Industries, Ltd., 127-04122, lot.KSG7724) with 25 mM CaCl 2-
  • mice were allowed free access to the diet of Test Example 1 and a solution containing the bLF hydrolyzate.
  • the control group had free access to the same chow and water without bLF.
  • mouse ovalbumin (0VA, manufactured by Seikagaku Corporation) was immunized intraperitoneally with 4 mg of aluminum hydroxide.
  • Blood was collected on day 8 (day 26) after the second immunization, and antibodies in the serum were measured by ELISA.
  • spleen cells were collected for each individual. Splenocytes were cultured with OVA (0-400 g / ml) for 72 hours, and the levels of IFN- ⁇ and IL-4 in the culture supernatant were measured by ELISA.
  • the serum total IgE antibody level and the OVA-specific IgE level in the experimental group tended to be lower than those in the control group (FIGS. 10 and 11).
  • IL-12 is a relatively new cytoin, it is known to act on T cells and NK cells to induce the production of IFN- ⁇ (J. Exp. Med., 173). :
  • Stimulation of cell components such as LPS is effective, and the cells producing them include a wide variety of cells such as macrophages, B cells, and neutrophils.
  • the present inventors have studied peritoneal macrophages in a medium supplemented with bLF (manufactured by Wako). After culturing, the level of IL-12 in the culture supernatant was measured by ELISA.
  • mice fed a MF diet (Oriental Yeast) freely were intraperitoneally injected with 2.5 ml of Chodari cholate medium (DIFC0), and 4 days after the activation of peritoneal macrophages Dulbecco containing 1% FCS in the peritoneal cavity
  • a phosphate buffer solution (Dulbeccos' PBS, Nissi) was injected to collect peritoneal cells. The cells were washed twice, and suspended in PBS again Dulbecco, it was injected into 96 ⁇ El plate (2X 10 5 cells /0.2 ml well), incubated for 1 hour Plate with C0 2 incubator.
  • lactoferrin induces macrophage IL-12 production.
  • mice BALB / c mice (3 weeks old, male) from SLC Japan were used for the experiment.
  • the mice were divided into groups of lactosylceramide-administered group (experimental group) and non-lactosylceramide-administered group control group, with three mice per group so that the average value and the variation in body weight were almost equal.
  • the ceramide used was lactosylceramide (derived from Shibata Milk, Wako Pure Chemical Industries, Ltd., biochemical reagent 126-04491, lot. ELK6191). Lactosylceramide is 0.5%
  • RPMI1640 medium Gibco, No.11875-093 containing 100 U / ml of penicillin, 100 g / ml of streptomycin, and 2-mercaptoethanol (5X101) (manufactured by Nippon Biotest Co., Ltd., lot.10086-1) was used. Culture was performed in quadruplicate, and b L F
  • Milk Epitres a treatment for milk allergy that does not contain whey protein as a raw material, was mixed with 0.01% of LF-LF in milk epitoles (manufactured by Meiji Dairies Co., Ltd.).

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Abstract

L'invention se rapporte à des inhibiteurs de production d'anticorps IgE d'origine mammalienne (et notamment humaine) et à des compositions immunomodulatrices contenant en tant que principe actif de la lactoferrine (LF) ou de l'hydrolysat de lactoferrine. Elle se rapporte également à des agents de potentialisation de la production d'IFN-η contenant de la lactoferrine ou de l'hydrolysat de lactoferrine et des céramides.
PCT/JP2001/000161 2000-01-14 2001-01-12 Inhibiteurs de production d'anticorps ige specifique d'un antigene WO2001051079A1 (fr)

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JP2001551502A JP4787445B2 (ja) 2000-01-14 2001-01-12 抗原特異的ＩｇＥ抗体産生抑制剤
AU25515/01A AU782539B2 (en) 2000-01-14 2001-01-12 Antigen-specific IgE antibody production inhibitors
NZ519957A NZ519957A (en) 2000-01-14 2001-01-12 Antigen-specific IgE antibody production inhibitors

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JP2000-005480 2000-01-14

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005350452A (ja) * 2004-05-14 2005-12-22 Meiji Milk Prod Co Ltd ＩｇＥ産生抑制作用を有する組成物およびＩｇＥ産生抑制方法
JP2010209043A (ja) * 2009-03-12 2010-09-24 Kuroisutaazu :Kk 皮膚外用剤
JP4795021B2 (ja) * 2002-12-06 2011-10-19 エイジェニックス インコーポレイテッド 敗血症治療における経口用ラクトフェリン

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EP0327461A1 (fr) * 1988-02-02 1989-08-09 Roussel-Uclaf Utilisation des protéines du lait pour la fabrication d'un médicament antiviral
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