WO2009072802A2 - Composition amincissante - Google Patents

Composition amincissante Download PDF

Info

Publication number
WO2009072802A2
WO2009072802A2 PCT/KR2008/007132 KR2008007132W WO2009072802A2 WO 2009072802 A2 WO2009072802 A2 WO 2009072802A2 KR 2008007132 W KR2008007132 W KR 2008007132W WO 2009072802 A2 WO2009072802 A2 WO 2009072802A2
Authority
WO
WIPO (PCT)
Prior art keywords
adipocytes
slimming
differentiation
composition according
composition
Prior art date
Application number
PCT/KR2008/007132
Other languages
English (en)
Other versions
WO2009072802A3 (fr
Inventor
Minsoo Noh
Seonmi Park
Hyeonju Yeo
Ji-Hae Lee
Bae-Hwan Kim
Jung Ju Kim
Original Assignee
Amorepacific Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Amorepacific Corporation filed Critical Amorepacific Corporation
Publication of WO2009072802A2 publication Critical patent/WO2009072802A2/fr
Publication of WO2009072802A3 publication Critical patent/WO2009072802A3/fr

Links

Classifications

    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • 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
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A23L33/15—Vitamins
    • 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
    • A23L33/16—Inorganic salts, minerals or trace elements
    • 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
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/06—Preparations for care of the skin for countering cellulitis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • This disclosure relates to a slimming composition, specifically to a slimming composition for inhibiting differentiation of adipocytes or reducing the level of lipid droplets in adipocytes.
  • Inter leukin-17 is a kind of cytokine known as cytotoxic T- lymphocyte-associated serine esterase 8 (CTLA8).
  • a variety of diseases including obesity and lipoma are known to be related with abnormal differentiation of adipocytes or abnormal level of lipid droplets in adipocytes. Researches are actively under way on the differentiation of adipocytes and the level of lipid droplets in adipocytes. Development of a factor or a substance capable of effectively controlling the differentiation of adipocytes or the level of lipid droplets in adipocytes is needed.
  • IL-17 inter leukin-17
  • the present invention has been made in view of the above problems, and it is an object of the present invention to solve the technical problems.
  • an object of the present invention is to provide a slimming composition comprising interleukin-17 (IL-17) inhibiting the differentiation of adipocytes as an effective ingredient.
  • IL-17 interleukin-17
  • Another object of the present invention is to provide a slimming composition comprising interleukin-17 (IL-17) reducing the level of lipid droplets in the differentiated adipocytes as an effective ingredient.
  • IL-17 interleukin-17
  • the present invention has been made in an effort to attain the aforesaid objects.
  • the present invention provides a slimming composition comprising interleukin-17 (IL-17).
  • interleukin-17 can effectively inhibit the differentiation of mesenchymal stem cells into adipocytes and reduce the level of lipid droplets in the differentiated adipocytes, so that the present invention provides superior slimming effect by comprising interleukin-17 (IL-17) as an effective ingredient may provide a particularly.
  • Figs. 1 to 4 are micrographs and graphs showing the effect of inhibiting differentiation of adipocytes by interlukin-17A (IL-17A) or IL-
  • Figs. 5 to 10 are graphs showing the change of expression of IL-17RA and IL-17RC mRNAs by IL-17A or IL-17F and the change of expression of peroxisome proliferator activating receptor Y (PPARY) mRNA, fatty acid binding protein 4 (FABP4) and adiponectin mRNAs in cells treated with IL-17A; ⁇ 13> Figs. 11 and 12 are graphs showing the effect of inhibiting differentiation of adipocytes by IL-17A observed with anti-IL-17A; ⁇ 14> Figs. 13 to 15 are micrographs and graphs showing the level of lipid droplets in adipocytes; ⁇ i5> Figs.
  • 16 to 19 are graphs showing the control of IL-6 and IL-8 genes in differentiated adipocytes by IL-17A; and ⁇ 16> Fig. 20 shows the decrease of adipose tissue in obesity-induced C57BL/6 mice fed with a high fat diet for a month, 7 days after the injection of IL- 17A into right epididymal adipose tissue. [Best Mode]
  • the term "slimming” has a broad meaning, including, not only ameliorating or preventing obesity, but also preventing and treating of diseases related with the increase of adipose tissue, reducing body weight for cosmetic or beauty treatment, ameliorating or preventing decreased elasticity due to increase of adipose tissue, or maintaining captivating body and smooth skin, and not specially limited unless contrary to the aforesaid purposes.
  • a composition comprising interleukin- 17 (IL-17), especially one or more selected from a group consisting of IL-17A and IL-17F, as an effective ingredient can inhibit differentiation of mesenchymal stem cells into adipocytes and reduce the level of lipid droplets in the differentiated adipocytes.
  • IL-17 interleukin- 17
  • IL-17 is known to enhance the expression of the cytokines IL-6 and IL-8 and granulocyte colony stimulating factor (G-CSF), which are known to affect the differentiation of the hematopoietic system in human fibroblasts (Yao et al., Human IL-17: a novel cytokine derived from T cells. /. Immun. 155: 5483- 5486, 1995). Further, IL-17 controls T-cell immune response which is related with allergic reactions. It was demonstrated from an experiment using IL-17- deficient mice (Nakae et al . , Suppression of immune induction of collagen- induced arthritis in IL-17-deficient mice. J. Immun. 171: 6173-6177, 2003).
  • G-CSF granulocyte colony stimulating factor
  • IL-17 presumably affects the onset of arthritis (Nakae et al., IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-I receptor antagonist. Proc. Nat. Acad. Sci. 100: 5986-5990, 2003).
  • IL-17 is present in higher level in the synovial fluid of patients with rheumatoid arthritis than patients with osteoarthritis
  • IL-17 is presumably closely related with the onset of rheumatoid arthritis (Kotake et al., IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J. Clin. Invest. 103: 1345-1352, 1999).
  • the IL-17 may include one or more selected from a group consisting of, for example, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F.
  • a composition comprising one or more selected from a group consisting of IL-17A and IL-17F, especially IL-17A, as an effective ingredient may provide a particularly superior slimming effect.
  • a composition comprising IL-17, especially IL-17A or IL-17F, as an effective ingredient may inhibit the differentiation of adipocytes.
  • the composition may provide an effect of preventing or treating diseases related with hypertrophic adipose tissue, or reducing adipose tissue for cosmetic or beauty treatment.
  • the diseases related with hypertrophic adipose tissue are not particularly restricted. For example, they may include obesity and lipoma.
  • adipocytes-related gene(s) selected from a group consisting of peroxisome proliferator activating receptor y (PPARy) mRNA, fatty acid binding protein 4 (FABP4) mRNA and adiponectin mRNA decreases when adipocytes treated with IL-17A or IL-17F differentiate. This may mean that the differentiation of adipocytes can be effectively inhibited by IL-17A or IL- 17F.
  • the differentiation of adipocytes may refer to the differentiation of preadipocyte cells or mesenchymal stem cells of an animal, particularly a mammal, into adipocytes. In particular, it may refer to the differentiation of human mesenchymal stem cells into adipocytes.
  • the mesenchymal stem cells may be differentiated into adipocytes by a manner similar to that employed to differentiate preadipocyte cells taken from the subcutaneous tissue into complete adipocytes, they are widely used in the researches on the differentiation of adipocytes.
  • the mesenchymal stem cells that can be differentiated into adipocytes are distributed in most of the body tissues.
  • the mesenchymal stem cells which are known to be able to differentiate into not only adipocytes but also other types of cells, including chondrocytes and osteocytes, have similar properties or characteristics in general, although there are some variations depending on what tissue they originate from.
  • the mesenchymal stem cells may be the mesenchymal stem cells derived from human bone marrow.
  • the composition may reduce the size and number of lipid droplets in differentiated adipocytes.
  • measurement of the level of lipid droplets and the degree of lipid decomposition through glycerol concentration after treatment with IL-17, particularly IL-17A exhibits that the size and number of lipid droplets decrease and that the lipid decomposition in adipocytes decrease remarkably.
  • the composition may be prepared into a cosmetic composition, a health food composition or a pharmaceutical composition.
  • the cosmetic composition for slimming may be prepared into, for example, skin lotion, nourishing lotion, massage cream, nourishing cream, pack, gel, body lotion, body cream, body oil or body essence, but not limited thereto.
  • Those skilled in the art will may include ingredients other than IL-17A or IL-17F in each form of cosmetic composition, depending on the particular preparation form or purpose of use, without difficulties.
  • the health food composition for slimming may be prepared into for example, tablet, granule, drink, caramel, diet bar, or the like, but not limited thereto.
  • Those skilled in the art will may include ingredients other than IL-17A or IL-17F in each form of health food composition, depending on the particular preparation form or purpose of use, without difficulties. The addition of other ingredients may result in a synergic effect.
  • the pharmaceutical composition for slimming may further include a pharmaceutic adjuvant such as antiseptic, stabilizer, hydration agent, emulsification promoter, salt and/or buffer for control of osmotic pressure, and the like, or other pharmaceutically and therapeutically useful substance. It may be prepared into a preparation form for oral or parenteral administration, according to common methods.
  • a pharmaceutic adjuvant such as antiseptic, stabilizer, hydration agent, emulsification promoter, salt and/or buffer for control of osmotic pressure, and the like, or other pharmaceutically and therapeutically useful substance. It may be prepared into a preparation form for oral or parenteral administration, according to common methods.
  • Preparation forms for oral administration include, for example, tablet, pill, hard and soft capsule, liquid, suspension, emulsion, syrup, granule, and the like. These preparation forms may contain, in addition to the effective ingredient, a diluent (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine) or a lubricant (e.g., silica, talc, stearic acid, magnesium stearate, calcium stearate and polyethylene glycol).
  • a diluent e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine
  • a lubricant e.g., silica, talc, stearic acid, magnesium stearate, calcium stearate and polyethylene glycol.
  • the tablet may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methyl cellulose, sodium carboxymethyl cellulose and polyvinylpyrrolidone. Depending on occasions, it may contain a pharmaceutic adjuvant such as a disintegrant , e.g., starch, agar, alginic acid or sodium alginate, an absorbent, a colorant, a flavor, a sweetener, or the like.
  • a disintegrant e.g., starch, agar, alginic acid or sodium alginate, an absorbent, a colorant, a flavor, a sweetener, or the like.
  • the tablet may be prepared according to common mixing, granulation or coating methods.
  • a typical preparation form for parenteral administration is an injection. Isotonic aqueous solution or suspension may be used. The preparation form for parenteral administration may be administered through a parenteral route or topically at an area rich in adipose tissue, with a dose of about 0.00001 to 0.01 mg/kg, particularly about 0.00001 to 0.001 mg/kg.
  • the dose of the effective ingredient will be easily determined by those skilled in the art.
  • a general dose is about 0.001 to 2,000 mg/kg/day, particularly about 0.5 to 2.5 mg/kg/day.
  • the actual dose will be determined considering various related factors, including severity of disease, selected administration route, age, sex, body weight and physical conditions of the subject, or the like.
  • the aforesaid dose does not limit the scope of this disclosure in any means.
  • the effective ingredient IL-17A or IL-17F may be included in an amount of 0.001-100 wt% based on the total weight of the composition.
  • the effective ingredient when included in an amount of 100 wt% based on the total weight of the composition, it means that the protein IL-17A or IL-17F itself may be used as the slimming composition as converted into a form adequate to provide a slimming effect.
  • the IL-17 may be derived from a mammal, particularly from human, although not limited thereto. It may be either a recombinant IL-17 prepared through a recombinant technique or a purified natural IL-17. Particularly, it may be an IL-17 having i) an amino acid sequence of SEQ ID NO: 1; ii) a fragment of the amino acid sequence of SEQ ID NO: 1 with the same slimming activity as that of SEQ ID NO: 1; or iii) variant of the amino acid sequence of SEQ ID NO: 1 with an identity of at least 95% with the sequence of SEQ ID NO: 1 and the same slimming activity as that of SEQ ID NO: 1.
  • fragment refers to one having a slimming activity. Such fragments may be produced by known a restriction enzyme or recombinant technique.
  • variant refers to an amino acid with at least one of its complementarity changed. Those skilled in the art will understand that all the variants fabricated from the amino acids disclosed herein and confirmed to have a slimming activity by specifically binding to IL-17 having a slimming activity through tests are included in the scope of this disclosure.
  • the variants include those in which the overall molecular structure of the amino acid sequence is conserved. Given informations on the properties of individual amino acids, those skilled in the art will recognize some reasonable substitutions. These conservative substitutions may be performed based on, for example, polarity, charge, solubility, hydrophobicity, hydrophilicity and/or amphiphilicity of related residues.
  • amino acids may be classified into nonpolar (hydrophobic) amino acids, polar and neutral amino acids, positively charged (basic) amino acids, and negatively charged (acidic) amino acids, depending on polarity.
  • Nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan and methionine.
  • Polar and neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine and glutamine.
  • Positively charged (basic) amino acids include arginine, lysine and histidine.
  • negatively charged (acidic) amino acids include aspartate and glutamate. Substitutions may be made in each group.
  • sequence may include not only the sequence of SEQ ID NO: 1 which encodes the amino acid disclosed herein but also its variant.
  • the "variant” may have a sequence identity of at least 80%. Further, it may have a sequence identity of at least 90% or at least 95%. Of the variants having such identity, those that are hybridized under very strict conditions are included. [Mode for Invention]
  • hBM-MSCs Human bone marrow mesenchymal stem cells purchased from Lonza, Inc. (Walkersville, MD, USA) are cultured following the company's instructions. More specifically, hBM-MSCs are cultured in a low- concentration glucose (1 g/L) culture medium (Dulbecco's modified Eagle's medium; DMEM) (Invitrogen, Carlsbad, CA, USA) containing 10% fetal bovine serum (FBS), 1% penicillin/streptomycin and 1% GlutaMAX. When the cell density in the culture dish reaches 100%, the condition under which differentiation into adipocytes proceeds is provided.
  • DMEM Dulbecco's modified Eagle's medium
  • FBS fetal bovine serum
  • penicillin/streptomycin 1% GlutaMAX
  • hBM-MSCs culture medium high-concentration glucose (4.5 g/L) culture medium
  • IDXT troglitazone
  • 25 ng/mL IL-17A, IL-17F or IL-22 is further added to the medium in addition to IDXT when inducing differentiation of adipocytes.
  • the degree of differentiation of adipocytes is determined as follows. After staining the adipocytes with Oil Red 0, Oil Red 0 is removed using 100% isopropanol solution. Then, absorbance is measured at 500 nm. The result is shown in Fig. 2.
  • the group which is treated with IL-17A or IL-17F when compared with the control group which is treated only with IDXT, the group which is treated with IL-17A or IL-17F can inhibit the differentiation by about 77.6% and about 45.6%, respectively.
  • the group treated with 25 ng/mL IL-22 does not show a statistically significant effect of inhibiting the differentiation of adipocytes.
  • IL-17A exhibits the effect of inhibiting differentiation in a concentration-dependent manner. The result is shown in Fig. 4.
  • ⁇ 56> hBM-MSCs are induced to differentiate into adipocytes in the same manner as Test Example 1.
  • the cells are treated with 1 ng/mL IL-17 for 7 days, and RNAs are isolated from the cells using Trizol reagent (Invitrogen, Carlsbad, CA, USA).
  • the isolated RNAs are further purified using Qiagen RNeasy kit (Qiagen, Valencia, CA), and the quality of the RNAs are investigated using Agilent 2100 BioAnalyzer (Agilent Technologies, Santa Clara, CA, USA).
  • cDNAs are synthesized form the RNAs using Superscript Reverse Transcriptase (RT) II kit (Invitrogen, Carlsbad, CA), and are analyzed quantitatively through real-time reverse transcription polymerase chain reaction (Q-RT-PCR). It is investigated whether there is a change in the expression of IL-17RA and IL-17RC mRNAs, which are transmembrane receptor proteins induced by IL-17A at the early stage of differentiation of adipocytes and known to play an important role in IL-17A and IL-17F signaling, using TaqManBE gene expression assay kit (Applied Biosystems, Foster City, CA). The result is shown in Figs. 5 and 6.
  • ⁇ 60> Referring to Figs. 7 to 9, 5 days after the commencement of differentiation of adipocytes, mRNA expression level of PPARy, FABP4 and adiponectin decreases significantly in the cells treated with IDXT and IL-17A as compared to the IDXT control group.
  • ⁇ 6i> secretion of the protein adiponectin decreases significantly when the same cell culture medium used for the Q-RT-PCR analysis is treated with IL-17A, as compared to the control group treated only with IDXT.
  • ⁇ 65> Referring to Fig. 11, 250 ng/mL anti ⁇ IL-17A cancels the inhibition of the differentiation of adipocytes by IL-17A.
  • adiponectin level in hBM-MSCs cultured under different adipose formation conditions is determined by ELISA. The result is shown in Fig. 12.
  • ⁇ 66> Referring to Fig. 12, the effect of inhibiting the secretion of adiponectin by IL-17A is remarkably decreased by the anti-IL-17A antibody. Therefore, it is confirmed that IL-17A plays an important role in inhibiting the differentiation of adipocytes in hBM-MSCs.
  • hBM-MSCs are cultured, induced to differentiate into adipocytes and treated with 25 ng/mL IL-17A in the same manner as Test Example 1.
  • the hBM- MSCs are induced to differentiate into adipocytes for 15 days.
  • 50% or more of the cells differentiate into adipocytes treatment is made with IL- 17A for 7 days.
  • IL-17A decreases the size and number of lipid droplets in differentiated adipocytes.
  • concentration of glycerol in the supernatant obtained from the culture medium of the differentiated adipocytes is measured. The result is shown in Fig. 15.
  • IL-17A remarkably increases lipolysis in adipocytes. Therefore, it is confirmed that IL-17A can regulate the metabolic state of differentiated adipocytes by controlling lipolysis in the differentiated adipocytes.
  • ⁇ 77> when compared with untreated hBM-MSCs, transcription of IL-6 is down-regulated in the condition of differentiation in the presence of IDXT.
  • the level of IL-6 mRNA increases remarkably.
  • the transcription level of IL-8 increases remarkably as differentiation of adipocytes proceeds, as compared to the IDXT control group.
  • IL-17F leads to up-regulation of the IL-6 mRNA level. But, the difference between the untreated cells and the cells treated with IL-17F is not significant. IL-8 shows similar pattern in both protein secretion and gene expression when treated with IL-17A and IL- 17F.
  • IL-17A regulates the production of IL-6 and IL-8 in differentiated adipocytes derived from hBM-MSCs.
  • IL-17A is prepared for injection by dissolving 1 ⁇ g of IL-17A in 1 mL of PBS followed by sterilization.
  • the mice in one test group are anesthetized using ketamine, and 0.1 mL of the prepared IL-17A solution is injected at the epididymal adipose tissue (epididymal fat pad) of the anesthetized mice, using a 26-guage syringe.
  • Only PBS is injected to the C57BL/6 mice in the control group using the same procedure.
  • mice are fed with the high fat diet for 7 more days. The mice are sacrificed after weighing body weight.
  • Cream is prepared according to the fol lowing compos i t ion.
  • Cosmetic essence is prepared according to the following composition.
  • Powder is prepared by mixing the following ingredients and filling them in an airtight pouch.
  • ⁇ i33> Tablet is prepared by mixing the following ingredients and following a common tablet making procedure.
  • Capsule is prepared by filling the following ingredient in a gelatin capsule.
  • ⁇ i50> Injection is prepared according to a common method, with a composition of an ampule (2 mL) as follows-'
  • Liquid is prepared according to a common method. The following ingredients are dissolved in purified water and an adequate amount of lemon flavor is added. After mixing, purified water is added to make a final volume of 100 mL. The prepared liquid is filled in a brown bottle and sterilized.
  • Health food is prepared according to the following composition. Changes may be made on the contents of vitamins and minerals. The following ingredients are mixed according to a common method to prepare granules.
  • Health drink is prepared according to a common method. The following ingredients are mixed and heated at 85 ⁇ C for about 1 hour while stirring. The resultant solution is filtered and filled in a sterilized 2 L container. After sealing and sterilizing, the solution is stored in a refrigerator before being used to prepare a health drink.
  • the composition may be changed considering geological or ethnical tastes, such as the age group of consumers, country, purpose of use, or the like.

Abstract

Composition amincissante contenant de l'interleukine-17 (Il-17) comme principe actif. Ladite composition peut procurer un effet amincissant supérieur grâce à la capacité du principe actif d'inhiber la différentiation des adipocytes et de réduire le niveau des gouttelettes lipidiques dans les adipocytes différentiés.
PCT/KR2008/007132 2007-12-03 2008-12-03 Composition amincissante WO2009072802A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR20070124600 2007-12-03
KR10-2007-0124600 2007-12-03

Publications (2)

Publication Number Publication Date
WO2009072802A2 true WO2009072802A2 (fr) 2009-06-11
WO2009072802A3 WO2009072802A3 (fr) 2009-09-03

Family

ID=40718346

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2008/007132 WO2009072802A2 (fr) 2007-12-03 2008-12-03 Composition amincissante

Country Status (2)

Country Link
KR (1) KR101616995B1 (fr)
WO (1) WO2009072802A2 (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005508393A (ja) * 2001-11-09 2005-03-31 アーテセル・サイエンシズ・インコーポレーテツド 胚および成人幹細胞をサポートするための間質細胞の使用の方法および組成物
CA2539253A1 (fr) * 2003-09-19 2005-03-31 Novo Nordisk A/S Nouveaux derives de glp-1
GB0417487D0 (en) * 2004-08-05 2004-09-08 Novartis Ag Organic compound

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ATSUHIRO OGAWA ET AL.: 'Neutralization of interleukin-17 aggravates dextran sulfate sodium- induced colitis in mice' CLINICAL IMMUNOLOGY vol. 110, no. 1, 2004, pages 55 - 62 *
ERIC P. K. MENSAH-BROWN ET AL.: 'IL-23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocin' EUROPEAN JOURNAL OF IMMUNOLOGY vol. 36, no. 1, 2006, pages 216 - 223 *

Also Published As

Publication number Publication date
KR20100111288A (ko) 2010-10-14
WO2009072802A3 (fr) 2009-09-03
KR101616995B1 (ko) 2016-06-07

Similar Documents

Publication Publication Date Title
KR102436084B1 (ko) 신규 펩티드 및 이를 포함한 조성물
KR101802411B1 (ko) Ｆａｍ１９ａ５ 단백질을 포함하는 비만 예방 또는 치료용 조성물 및 이를 이용한 비만 치료제의 스크리닝 방법
JP2010513405A (ja) 二量体プロラクチンレセプターリガンド
KR20160089523A (ko) 전립선 암 치료용 조성물
JP6944046B2 (ja) しわ改善活性を示すペプチド及びその用途
EP3189849B1 (fr) Peptide pour prévenir ou traiter l'obésité
JP2018524290A (ja) 新規ペプチド及びこれを含む組成物
JP6573293B2 (ja) 炎症性疾患の予防または治療用ペプチド及びこの用途
KR20120058865A (ko) 사과줄기세포 추출물을 함유하는 지방유래 줄기세포의 줄기세포성 증진용 조성물
Lee et al. Poly-γ-glutamic acid suppresses osteoclastogenesis in human osteoclast precursors and prevents joint damage in a collagen-induced murine arthritis model
KR101826690B1 (ko) 단백질 타이로신 탈인산화효소 억제제를 포함하는 신경염증성 질환의 예방 또는 치료용 조성물
KR101986774B1 (ko) 과면역 반응에 의해 유발되는 염증성 질환 치료용 조성물
CN107250360B (zh) c-Rel特异性siRNA及其用于防治自身免疫性银屑病的应用
KR101859499B1 (ko) 세포외기질을 모사한 지방유래 줄기세포의 줄기세포성 증진용 조성물
WO2009072802A2 (fr) Composition amincissante
KR101935199B1 (ko) 디플로르에토하이드록시카르마롤(Diphlorethohydroxycarmalol, DPHC)를 이용한 운동 능력 개선용 조성물
KR20200067745A (ko) Fas 신호전달 억제용 펩티드를 포함하는 비만, 지방간 또는 지방간염의 예방 또는 치료용 약학적 조성물
JP2002516339A5 (ja) LAIT(sCD14)蛋白質による抗生物質ペプチドの誘導
KR20110021252A (ko) 카페인산 페네틸에스테르를 함유하는 비만 예방용 식품 조성물 또는 비만 치료용 제약 조성물
KR102055879B1 (ko) 감태추출물을 포함하는 식이조절 조성물 및 이의 제조방법
AU2020420368A1 (en) Composition for reinforcing function of stem cell
JP6649050B2 (ja) 幹細胞の未分化状態維持剤及び増殖促進剤
AU2005237323A1 (en) IL6R/IL6 chimera for therapy of chemotherapy-induced peripheral neuropathy
KR102469920B1 (ko) Cd146 단백질을 포함하는 근육 노화 관련 질환의 예방 또는 치료용 조성물
TWI818286B (zh) 包括表現腫瘤壞死因子可誘導基因６的間葉幹細胞之組成物及藥物組成物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08856935

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 20107017336

Country of ref document: KR

Kind code of ref document: A

122 Ep: pct application non-entry in european phase

Ref document number: 08856935

Country of ref document: EP

Kind code of ref document: A2