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WO2020111171A1 - Composition permettant de favoriser l'angiogenèse - Google Patents

Composition permettant de favoriser l'angiogenèse Download PDF

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Publication number
WO2020111171A1
WO2020111171A1 PCT/JP2019/046524 JP2019046524W WO2020111171A1 WO 2020111171 A1 WO2020111171 A1 WO 2020111171A1 JP 2019046524 W JP2019046524 W JP 2019046524W WO 2020111171 A1 WO2020111171 A1 WO 2020111171A1
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WIPO (PCT)
Prior art keywords
angiogenesis
promoting
composition
promoting angiogenesis
peptide
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Application number
PCT/JP2019/046524
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English (en)
Japanese (ja)
Inventor
高野　義彦
彩加 宮本
拓 中埜
Original Assignee
雪印メグミルク株式会社
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Priority to JP2020557814A priority Critical patent/JPWO2020111171A1/ja
Publication of WO2020111171A1 publication Critical patent/WO2020111171A1/fr

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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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/19—Dairy proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids

Definitions

  • the present invention relates to a composition for promoting angiogenesis, a skin care agent, a food/beverage product for promoting angiogenesis, a supplement for promoting angiogenesis, and a cosmetic composition for promoting angiogenesis, which are useful for preventing aging of blood vessel function and the like.
  • Angiogenesis (regeneration) is important for the healthy maintenance of various organs.
  • Angiogenesis is the formation of new blood vessels from existing blood vessels, the process of which is initiated by the regulation of pericyte (mural cell) detachment from the vessel wall by Ang-2 (angiopoietin-2).
  • Ang-2 angiopoietin-2
  • VEGF vascular endothermic growth factor
  • VEGF has the functions of inducing proliferation and maintenance of survival of vascular endothelial cells, enhancing vascular permeability, regulating blood pressure, migration by platelets, chemotaxis to macrophages and the like.
  • a substance that enhances VEGF expression in vascular endothelial cells can be expected as a composition for promoting angiogenesis to prevent or improve skin aging, hair growth, myocardial function improvement, bone/cartilage function improvement, and brain function improvement.
  • substances that enhance the expression of VEGF soybean-derived preparations, extracts from plants and the like (Patent Document 1), and peptides (Patent Document 2) have been found.
  • As components contained in milk that promote angiogenesis Angiogenin-2 and Lactadherin have been reported (Non-Patent Document 1). However, there is no report as a peptide.
  • the object of the present invention is to provide an unprecedented composition for promoting angiogenesis.
  • Another object of the present invention is to provide a skin care agent, a food or drink for promoting angiogenesis, a supplement for promoting angiogenesis, and a cosmetic for promoting angiogenesis, which contain such a substance.
  • the inventors of the present invention have eagerly searched for a substance which is widely contained in food materials and has an action of promoting angiogenesis. Then, they found that the peptide consisting of LSFNPTQLEEQCHI (SEQ ID NO: 1) and its degradation product in the amino acid sequence of ⁇ -lactoglobulin promote angiogenesis, and completed the present invention. That is, the present invention includes the following aspects.
  • a composition for promoting angiogenesis which comprises, as an active ingredient, a peptide comprising the amino acid sequence represented by SEQ ID NO: 1 and/or its degradation product having angiogenic activity.
  • composition for promoting angiogenesis according to ⁇ 1>, wherein the degradation product is obtained by degrading a peptide having the amino acid sequence represented by SEQ ID NO: 1 with a protease. .. ⁇ 3>
  • the proteolytic enzyme is one or more selected from the group consisting of trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, and V8 protease ⁇ 2>, A composition for promoting angiogenesis.
  • angiogenesis promoting supplement, an angiogenesis promoting food or drink, or an angiogenesis promoting cosmetic comprising the angiogenesis promoting composition according to any one of ⁇ 1> to ⁇ 3>.
  • the cosmetic for promoting angiogenesis according to ⁇ 4> which is a skin care agent to be applied to the skin surface.
  • the skin care agent according to ⁇ 5> wherein the skin care is prevention and/or improvement of rough skin.
  • the skin care agent according to any one of ⁇ 5> to ⁇ 7> which is a face cleanser, a cream, an emulsion, a beauty essence, or a lotion.
  • a peptide comprising the amino acid sequence represented by SEQ ID NO: 1 (hereinafter, may be referred to as a peptide of SEQ ID NO: 1) and/or an angiogenesis-promoting substance containing a decomposition product thereof having an angiogenesis-promoting activity as an active ingredient
  • Compositions, foods and drinks for promoting angiogenesis, supplements for promoting angiogenesis, and cosmetics for promoting angiogenesis are provided.
  • the composition for promoting angiogenesis of the present invention has an action of promoting angiogenesis. Therefore, it is useful for dryness, rough skin, wrinkles, and sagging.
  • FIG. 5 is a graph showing the effect of a gel filtration fraction of a tryptic digest of ⁇ -lactoglobulin ( ⁇ -LgT) on VEGF mRNA expression.
  • FIG. 3 shows the results of reverse phase chromatography of the gel filtration activity fraction of a tryptic digest of ⁇ -lactoglobulin. It is a graph which shows the influence on the VEGF mRNA expression by the sample A corresponding to the peptide of SEQ ID NO: 1 separated by reverse phase chromatography. It is a graph which shows the influence on the VEGF mRNA expression by sample B corresponding to the peptide of SEQ ID NO: 1 and sample C which is a degradation product thereof. It is a figure which shows the measurement result of the angiogenesis promotion activity of the sample B corresponding to the peptide of sequence number 1.
  • the inventors of the present invention have eagerly searched for a substance which is widely contained in food materials and has an action of promoting angiogenesis.
  • the present invention found that the peptide of SEQ ID NO: 1 and its degradation product in the amino acid sequence of ⁇ -lactoglobulin promote angiogenesis by promoting the expression of mRNA of VEGF which is an angiogenesis regulator. Has been completed.
  • the peptide of SEQ ID NO: 1 used in the present invention has angiogenesis promoting activity.
  • the peptides used in the present invention may be of any origin.
  • ⁇ -lactoglobulin derived from human and bovine can be used as a raw material for obtaining the peptide of SEQ ID NO: 1.
  • the gene sequence of ⁇ -lactoglobulin has already been elucidated. Therefore, it can be produced by gene recombination, and cells derived from cells recovered from the cell culture medium can also be used.
  • ⁇ -lactoglobulin can be processed from raw milk, milk powder, skim milk, reduced milk, etc. by heat treatment, salting treatment, ethanol treatment, various chromatographic treatments such as ion exchange chromatography and gel filtration chromatography, and ultrafiltration treatment. It is also possible to obtain.
  • the peptide of SEQ ID NO: 1 can be obtained by treating ⁇ -lactoglobulin with a protease.
  • proteolytic enzymes include trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, or V8 protease. Moreover, you may use 1 or more types of these proteolytic enzymes.
  • the proteolytic enzyme degradation product of ⁇ -lactoglobulin itself containing the peptide of SEQ ID NO: 1 can also be used as the composition for promoting angiogenesis of the present invention.
  • the fraction containing the peptide of SEQ ID NO: 1 can be used as the composition for promoting angiogenesis of the present invention.
  • the fraction containing the peptide of SEQ ID NO: 1 in the proteolytic enzyme degradation product of ⁇ -lactoglobulin is, for example, a Superdex peptide HR10/30 gel filtration column (GE Healthcare Japan KK) and an AKTA chromatography system (GE Healthcare). Care Japan Co., Ltd.).
  • a degradation product of the peptide of SEQ ID NO: 1 having angiogenesis promoting activity can be obtained by treating the peptide of SEQ ID NO: 1 with a protease.
  • proteolytic enzymes include trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, or V8 protease.
  • the degradation product of the peptide of SEQ ID NO: 1 having angiogenic activity can be prepared, for example, by the following procedure.
  • protease A one or more selected from the group consisting of trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, and V8 protease may be used.
  • the peptide of SEQ ID NO: 1 may be chemically synthesized by a commercially available peptide synthesizer.
  • the degradation product of the peptide of SEQ ID NO: 1 having angiogenesis promoting activity can be a peptide fragment or partial peptide of the peptide of SEQ ID NO: 1 having angiogenesis promoting activity.
  • the degradation product of the peptide of SEQ ID NO: 1 having angiogenesis promoting activity is a polypeptide having one or several amino acids deleted in the amino acid sequence represented by SEQ ID NO: 1 and having angiogenesis promoting activity. You can
  • the composition for promoting angiogenesis of the present invention exerts an effect of promoting angiogenesis by, for example, oral administration or application.
  • the peptide of SEQ ID NO: 1 which is an active ingredient and/or its degradation product having angiogenesis promoting activity can be used as it is, but the conventional method is used. According to the above, it can be used by formulating into foods and drinks, powders, granules, tablets, capsules, drinks and the like.
  • the peptide of SEQ ID NO: 1 and/or its degradation product having angiogenesis-promoting activity is relatively stable to heat. Therefore, it is also possible to heat sterilize the raw material containing the peptide of SEQ ID NO: 1 and/or its degradation product having angiogenesis-promoting activity under the conditions that are usually performed.
  • composition for promoting angiogenesis of the present invention can be incorporated into an oral preparation.
  • oral agents such as powders, granules, tablets and capsules are prepared by a conventional method using excipients such as starch, lactose, sucrose, mannitol, carboxymethyl cellulose, corn starch and inorganic salts. Is possible.
  • excipients such as starch, lactose, sucrose, mannitol, carboxymethyl cellulose, corn starch and inorganic salts.
  • a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a colorant, a fragrance and the like may be appropriately used in this type of formulation.
  • binder examples include starch, dextrin, gum arabic, gelatin, hydroxypropyl starch, sodium carboxymethyl cellulose, methyl cellulose, crystalline cellulose, ethyl cellulose, polyvinylpyrrolidone.
  • disintegrant examples include starch, hydroxypropyl starch, carboxymethyl cellulose, sodium carboxymethyl cellulose, crosslinked sodium carboxymethyl cellulose, crystalline cellulose and the like.
  • surfactant soybean lecithin, sucrose fatty acid ester, etc.
  • talc wax, sucrose fatty acid ester, hydrogenated vegetable oil, etc.
  • silicic acid as a fluidity promoter, dry aluminum hydroxide, Magnesium silicate etc. are mentioned.
  • the composition for promoting angiogenesis of the present invention can be incorporated into cosmetics for application on the skin surface.
  • the composition for promoting angiogenesis of the present invention is applied, it is prepared into various dosage forms such as a liquid agent, a solid agent, a semi-solid agent, etc. by blending it with a commonly used known component depending on the purpose of use. It is possible.
  • Preferred forms of the composition include ointments, gels, creams, sprays, patches, lotions and powders.
  • the composition for promoting angiogenesis of the present invention comprises a hydrocarbon such as petrolatum; a higher fatty acid lower alkyl ester such as stearyl alcohol and isopropyl myristate; an animal oil and fat such as lanolin; a polyhydric alcohol such as glycerin; a glycerin fatty acid ester; A surfactant such as monostearic acid or polyethylene glycol; a preservative such as methyl paraoxybenzoate or butyl paraoxybenzoate; an inorganic salt; a wax; a cosmetic or a pharmaceutical agent for promoting angiogenesis by mixing with a resin or the like be able to.
  • a hydrocarbon such as petrolatum
  • a higher fatty acid lower alkyl ester such as stearyl alcohol and isopropyl myristate
  • an animal oil and fat such as lanolin
  • a polyhydric alcohol such as glycerin
  • a glycerin fatty acid ester
  • the effective dose by oral administration of the composition for promoting angiogenesis of the present invention is, for example, 10 ⁇ g or more per adult per day. It is preferable to mix it in food or drink so as to ensure this required amount, or to administer it as a medicine. The administration can be divided into several times a day if necessary.
  • the effective amount of the composition for promoting angiogenesis of the present invention applied varies depending on the dosage form, but is preferably 0.001 to 2% by weight, more preferably 0.005 to 2% by weight based on the total amount of the composition to be applied.
  • the peptide of SEQ ID NO: 1 is used in an amount of 0.01% by weight, more preferably 0.01 to 1.5% by weight, further preferably 0.03 to 1% by weight, further preferably 0.03 to 0.8% by weight. It should be mixed. However, a compound such as a bath agent that is diluted at the time of use can be further added.
  • angiogenesis means forming a new blood vessel from an existing blood vessel.
  • promoting angiogenesis can include increasing the activity of forming a new blood vessel from an existing blood vessel in vitro or in vivo.
  • Promoter angiogenesis can include promoting the activity of expression and/or function of VEGF, which is a pro-angiogenic factor, and forming a capillary-like structure.
  • the VEGF expression-enhancing activity can be evaluated using the real-time PCR method, for example, in the following procedure. HUVEC cells are seeded on a 24-well plate at 1 ⁇ 10 5 cells/ml and cultured in Humedia-EG2 medium at 37° C. in a 5% CO 2 environment for 1 week.
  • the sample to be evaluated is dissolved in Humedia-EG2 medium (KURABO) and added to HUVEC cells.
  • Humedia-EG2 medium Humedia-EG2 medium
  • ISOGEN Natural Gene
  • the cell solution solubilized by pipetting is collected in a 1.5 ml tube.
  • 0.1 ml of chloroform is added to the collected cell liquid, and after sufficiently stirring, the upper layer (aqueous layer) separated into two layers is collected in a new 1.5 ml tube.
  • 0.25 ml of 2-propyl alcohol is added to the recovered liquid, and the mixture is left standing for 10 minutes. Then, it is centrifuged at 15,000 rpm and 4° C.
  • RNA solution is synthesized from 1 ⁇ g of RNA using the trade name “Takara PrimeScript TM RT reagent kit”.
  • Real-time PCR using SYBR Green (Takara SYBR Prime Ex Taq II) is performed using the obtained cDNA as a template.
  • the reaction conditions include initial denaturation at 95° C. for 30 seconds, denaturation at 95° C. for 5 seconds, annealing at 57° C. for 15 seconds, extension at 72° C. for 20 seconds, and a total of 40 cycles of reaction.
  • the primer the VEGF gene expression confirmation primer described in Table 1 is used.
  • the “skin care agent” means a drug or cosmetic that can maintain and/or improve the health condition of the skin by directly or indirectly applying to the skin surface using gauze or the like.
  • the skin care agent of the present invention is preferably liquid or gel, but for example, a solid one containing the composition for promoting angiogenesis of the present invention, such as a gauze, a mask, and a pack is also a skin care agent. included.
  • the skin care agent of the present invention preferably improves one or more of dryness, rough skin, wrinkles, and sagging of the target.
  • the skin care agent of the present invention is preferably a face wash, a cream, an emulsion, a beauty essence, or a lotion, more preferably a cream or a lotion.
  • the skin care agent of the present invention can be applied to the skin of the subject twice a day for 10 days or more.
  • the subject of administration of the skin care agent and the cosmetic for promoting angiogenesis of the present invention is not particularly limited, but it is intended for subjects having one or more symptoms selected from the group consisting of dry feeling, rough skin, wrinkles, and sagging. It is preferable to administer.
  • Another aspect of the present invention is to prepare a composition for promoting angiogenesis, which comprises the peptide of SEQ ID NO: 1 and/or its degradation product having angiogenic activity as an active ingredient, and the composition for promoting angiogenesis. It may be a cosmetic method for applying to the skin, preferably one or more improving methods selected from the group consisting of dry feeling, rough skin, wrinkles, and sagging of the target.
  • the skin care agent, angiogenesis-promoting supplement, angiogenesis-promoting food or drink, or angiogenesis-promoting cosmetic composition of the present invention can be filled in any container or can be packaged in any packaging material.
  • the angiogenesis-promoting effect of the peptide of SEQ ID NO: 1 and its degradation product can be evaluated by examining the effect of the addition of the peptide or its degradation product on mRNA expression of VEGF, which is an angiogenesis-promoting factor.
  • VEGF which is an angiogenesis-promoting factor
  • the effect of VEGF, which is an angiogenesis-promoting factor, on mRNA expression can be confirmed by a cell experiment using HUVEC which is a normal human umbilical vein vascular endothelial cell and a real-time PCR method.
  • Example 1 (Preparation of tryptic digest) A tryptic digest of ⁇ -lactoglobulin was prepared. ⁇ -lactoglobulin was dissolved in Mili-Q water to 30 mg/ml, and trypsin (Sigma-Aldrich Japan) was added to 0.1 mg/ml. After adjusting the pH to 8.0 with 1N NaOH, the mixture was reacted at 37° C. for 1 hour. Then, the pH was adjusted to 8.0 again with 1N NaOH, and the mixture was reacted at 37° C. for 1 hour. After further adjusting the pH to 8.0 with 1N NaOH, the mixture was reacted at 37° C.
  • this active fraction 1 ( ⁇ -LgTGF frac.1) was subjected to reverse phase chromatography using Proteonavi (OSAKASODA 4.6 ⁇ 250 mm) to obtain a peak as shown in FIG.
  • the peak corresponding to the peptide of No. 1 was collected and used as sample A.
  • the thus obtained peptide having an angiogenesis promoting action can be directly used as the angiogenesis promoting composition of the present invention.
  • RNA was synthesized from 1 ⁇ g of RNA using the trade name “Takara PrimeScript TM RT reagent kit”.
  • Real-time PCR using SYBR Green was performed using the obtained cDNA as a template.
  • the reaction conditions were 95° C. for 30 seconds for initial denaturation, 95° C. for 5 seconds for denaturation, 57° C. for 15 seconds for annealing, 72° C. for 20 seconds for extension, and a total of 40 cycles of reaction were performed.
  • Test Example 2 The effect of the peptide of SEQ ID NO: 1 (Sample B), which is a synthetic peptide purchased from GenScript, and the degradation product, Sample C, on mRNA expression of angiogenesis promoting factor was examined using a real-time PCR method. The method was based on the method described in Test Example 1.
  • sample C sample B was dissolved in Mili-Q water so as to have a concentration of 10 mg/ml, and protease A (Amano Pharmaceutical Co., Ltd.) was added so as to have a concentration of 0.1 mg/ml on the basis of the sample B solution, and the mixture was mixed at 37° C. After reacting for a time and deactivating the enzyme at 95° C.
  • Example 3 (Measurement of peptide angiogenic activity)
  • the angiogenesis-promoting activity of the synthetic peptide (Sample B) was measured using the Angiogenesis Assay Kit (PromoKine).
  • RGF BME PathClear (Cultrex) was placed in advance at 4° C. from the previous day, and the solution was thawed.
  • the Staining Dye Solution attached to the Angiogenesis Assay Kit (PromKine) was thawed at 4° C.
  • the Wash Buffer attached to the Angiogenesis Assay Kit was thawed at 37° C. Kept warm.
  • the thawed RGF BME PathClear was ice-cooled, and 100 ⁇ l/well was poured into a 96-well plate that was also cooled on ice, taking care not to let the temperature rise above 4°C. Then, the gel was solidified by incubating at 37° C. for 1 hour. On a solidified gel, 50 ⁇ g/ml ascorbic acid, 1 ⁇ g/ml hydrocortisone, 0.75 U/ml heparin, 10 mM L-glutamine, 5 ng/ml hEGF, 5 ng/ml hFGF-b were added to HuMedia EG2 medium (KURABO).
  • FIG. 5 what appears to be granular is the stained HUVEC cells. If formation of a capillary-like structure can be confirmed between HUVEC cells, it can be evaluated that the added component has angiogenic activity. As shown in FIG. 5, more initial capillary-like structure formation was observed when Sample B was added to HUVEC cells than in the control where Sample B was not added. Therefore, the synthetic peptide (Sample B) was found to have angiogenic activity.
  • Example 2 Beverages for promoting angiogenesis having the formulations shown in Table 2 were produced by a conventional method. The produced beverage had a good flavor and there was no problem such as precipitation.
  • Example 3 A dough having the composition shown in Table 3 was prepared by a conventional method, molded, and then baked to produce a biscuit for promoting angiogenesis.
  • Example 4 The angiogenesis promoter having the composition shown in Table 4 was produced by a conventional method.
  • Example 5 A lotion having the composition shown in Table 5 was produced by a conventional method.
  • Example 6 Creams having the formulations shown in Table 6 were produced by a conventional method.
  • Test Example 4 A practical use test was conducted using the lotion obtained in Example 5 and the cream obtained in Example 6.
  • the same formulation as in Examples 5 and 6 was used except that the peptide having the amino acid sequence LSFNPTQLEEQCHI (SEQ ID NO: 1) and its degradation product were removed. Twenty adult women with slackness and wrinkles on the face and a feeling of dryness were randomly assigned to two groups (groups A and B) and 20 women with rough skin on their hands.
  • the lotion of the present invention markedly improved the feeling of dryness as compared with the lotion of the comparative product, and the effects of improving rough skin, wrinkles and sagging were also confirmed. Therefore, it was demonstrated that the lotion of the product of the present invention is excellent in the effect of promoting angiogenesis. Further, the cream of the present invention also showed a remarkable improvement in dry feeling as compared with the cream of the comparative product, and it was clarified that it has an effect of suppressing natural deterioration such as rough skin.
  • angiogenesis promoters it is possible to provide angiogenesis promoters, angiogenesis promotion supplements, foods and drinks, and angiogenesis promotion cosmetics that are useful for preventing skin roughness, wrinkles, elasticity reduction, and the like. ..

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Abstract

La présente invention aborde le problème consistant à fournir une composition permettant de favoriser l'angiogenèse qui ne présente aucun problème de sécurité. La présente invention aborde également le problème consistant à fournir un supplément, un aliment et une boisson permettant de favoriser l'angiogenèse et un produit cosmétique permettant de favoriser l'angiogenèse comprenant chacun la substance susmentionnée.　Ces problèmes peuvent être résolus par : une composition permettant de favoriser l'angiogenèse, ladite composition contenant, en tant que principe actif, un peptide comprenant la séquence d'acides aminés représentée par SEQ ID NO: 1 et/ou un produit de décomposition de ce dernier présentant une activité favorisant l'angiogenèse ; et un agent de soin de la peau, un supplément, un aliment et une boisson permettant de favoriser l'angiogenèse ou un produit cosmétique permettant de favoriser l'angiogenèse comprenant chacun la composition susmentionnée permettant de favoriser l'angiogenèse.
PCT/JP2019/046524 2018-11-29 2019-11-28 Composition permettant de favoriser l'angiogenèse WO2020111171A1 (fr)

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JP2007217356A (ja) * 2006-02-17 2007-08-30 Wamiles Cosmetics Kk 海洋深層水濃縮物含有組成物及びその製造方法
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JP2011518864A (ja) * 2008-04-29 2011-06-30 ファーネクスト 血管新生の調節を通したアルツハイマー病および関連障害の処置のための新たな治療アプローチ
JP2012188384A (ja) * 2011-03-10 2012-10-04 Snow Brand Milk Products Co Ltd 美肌剤
JP2013166719A (ja) * 2012-02-15 2013-08-29 Dhc Co Ａｍｐｋ活性化剤
JP2016056116A (ja) * 2014-09-08 2016-04-21 株式会社ディーエイチシー コラーゲン産生促進用組成物

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005041811A (ja) * 2003-07-22 2005-02-17 Noevir Co Ltd 光毒性抑制剤、細胞賦活剤、及びｖｅｇｆ産生促進剤
JP2007217356A (ja) * 2006-02-17 2007-08-30 Wamiles Cosmetics Kk 海洋深層水濃縮物含有組成物及びその製造方法
JP2011518864A (ja) * 2008-04-29 2011-06-30 ファーネクスト 血管新生の調節を通したアルツハイマー病および関連障害の処置のための新たな治療アプローチ
US20090297545A1 (en) * 2008-05-27 2009-12-03 Universite Laval Immunomodulatory dairy peptides and uses thereof
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