WO2014203883A1 - Promoteur de production d'acide hyaluronique - Google Patents

Promoteur de production d'acide hyaluronique Download PDF

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Publication number
WO2014203883A1
WO2014203883A1 PCT/JP2014/066000 JP2014066000W WO2014203883A1 WO 2014203883 A1 WO2014203883 A1 WO 2014203883A1 JP 2014066000 W JP2014066000 W JP 2014066000W WO 2014203883 A1 WO2014203883 A1 WO 2014203883A1
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Prior art keywords
hyaluronic acid
lipocalin
acid production
production promoter
degradation product
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PCT/JP2014/066000
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English (en)
Japanese (ja)
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高野　義彦
晴彦 加藤
宏 上野
敏也 小林
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雪印メグミルク株式会社
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Publication of WO2014203883A1 publication Critical patent/WO2014203883A1/fr

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    • 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
    • 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
    • A23L2/66—Proteins
    • 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
    • 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
    • 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
    • A23L33/18—Peptides; Protein hydrolysates
    • 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
    • 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
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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
    • A61Q19/08—Anti-ageing preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists

Definitions

  • the present invention relates to a hyaluronic acid production promoter, a hyaluronic acid production promoting supplement, a food and drink, and a hyaluronic acid production promoting cosmetic useful for preventing rough skin, wrinkles, reduced elasticity, reduced joint function, and the like.
  • the skin is roughly composed of the epidermis present on the skin surface and the dermis present in the lower part of the epidermis.
  • the epidermis mainly has a barrier function that protects against foreign substances, pathogenic bacteria, and ultraviolet rays, and a function that protects the leakage of substances from the living body.
  • the dermis is about 15-40 times thicker than the epidermis and plays a role in maintaining the mechanical strength of the skin.
  • the dermis is a fiber component comprising 70% of the dry weight of collagen, but a substrate such as glycoprotein or proteoglycan exists between dermis fibers and skin fibroblasts.
  • Proteoglycans are macromolecules with a molecular weight of 105-106 or more, in which glycoproteins and mucopolysaccharides such as glycosaminoglycans are bound. Since dermal glycosaminoglycans are mainly composed of hyaluronic acid and dermatan sulfate, hyaluronic acid It can be said that it is the main matrix component in the dermis.
  • Hyaluronic acid mainly has a function of retaining the moisture of the skin, so it is considered that the decrease of the moisture content of the skin can be prevented by increasing the hyaluronic acid content in the dermis.
  • Many cosmetics containing hyaluronic acid have been proposed as an improving agent for the retention function.
  • the hyaluronic acid applied to the skin surface only exhibits a moisturizing effect on the skin surface, and cannot essentially improve the skin functional deterioration.
  • Patent Document 1 proposes a complex of hyaluronic acid and phospholipid.
  • no method for increasing hyaluronic acid in the body without ingesting hyaluronic acid is disclosed.
  • hyaluronic acid production promoters extracts obtained from hamachal, kanranized boswellia genus frankincense, sandalwood family sandalwood genus sandalwood, rose family rose genus damask rose, perilla family mannenro genus rosemary are disclosed. (Patent Documents 1 and 2)
  • hyaluronic acid in synovial fluid covers the surface of articular cartilage and helps smooth operation of joint functions.
  • the concentration of hyaluronic acid in normal human joint fluid is about 2.3 mg / mL.
  • the concentration of hyaluronic acid in joint fluid decreases to about 1.2 mg / mL, and at the same time, The viscosity is also significantly reduced.
  • hyaluronic acid content decreases in pyogenic arthritis and gouty arthritis as in the case of rheumatoid arthritis (Non-patent Document 1).
  • the amount of hyaluronic acid in the joint fluid is increased in order to improve the lubrication function, cover / protect articular cartilage, suppress pain, and improve the properties of pathological joint fluid.
  • Non-patent Document 2 when rheumatoid arthritis patients are given joint injection therapy with sodium hyaluronate, the above improvement has been observed (Non-patent Document 2).
  • Non-patent Document 3 the improvement effect by joint injection therapy of hyaluronic acid has been reported (Non-patent Document 3).
  • promotion of hyaluronic acid production is effective for the prevention and treatment of skin diseases such as rough skin, joint diseases such as rheumatoid arthritis, traumatic arthropathy, osteoarthritis, and osteoarthritis. Therefore, a supplement, cream or food or drink containing a hyaluronic acid production promoter that can be easily treated in daily life has been desired.
  • Lipocalin 2 (LCN2) and ⁇ -lactoglobulin are proteins belonging to the lipocalin family having eight ⁇ -barrel structures.
  • Lipocalin 2 (LCN2) also called human neutrophil gelatinase-binding lipocalin (NGAL)
  • NGAL human neutrophil gelatinase-binding lipocalin
  • Lipocalin 2 secreted from the liver has an antibacterial action by selectively binding to diderophore-Fe3 + to inhibit bacterial iron utilization and growth.
  • lipocalin 2 in plasma and blood can be used as a marker for inflammation and infection
  • lipocalin 2 in urine can be used as a marker for malignant tumors such as breast cancer.
  • Lipocalin 2 is known to be also contained in milk, but it has been reported that it is more contained in colostrum than in mature milk.
  • ⁇ -lactoglobulin is the major whey protein in milk. It has the ability to bind hydrophobic substances such as retinol, which is a useful physiologically active substance, and has excellent functional properties (emulsifying property, gelling property, foaming property).
  • Patent Literatures 1 and 2 because plant-derived raw materials are used, stable supply such as cultivation of hyaluronic acid production promoter raw materials is limited to a specific region, and fluctuations in supply due to the season are large. There is a problem that cannot be done. Therefore, the present invention provides a hyaluronic acid production promoter that can be taken orally, and provides a supplement for promoting hyaluronic acid production, a food and drink, and a cosmetic for promoting hyaluronic acid production containing such substances. Let it be an issue.
  • the present inventors diligently searched for a substance exhibiting hyaluronic acid production promoting action.
  • lipocalin family protein degradation obtained by degrading lipocalin family protein or lipocalin family protein was investigated.
  • the product has been found to increase the amount of hyaluronic acid produced, and the present invention has been completed. That is, the present invention includes the following aspects.
  • the hyaluronic acid production promoter according to (1) wherein the lipocalin family and / or lipocalin family degradation product is lipocalin 2 and / or lipocalin 2 degradation product.
  • a cosmetic comprising the hyaluronic acid production promoter according to any one of (1) to (6).
  • a hyaluronic acid production promoter with improved safety by using a lipocalin family protein and / or a lipocalin family protein degradation product as an active ingredient.
  • the hyaluronic acid production promotion effect by lipocalin 2 is shown. This compares the effects of lipocalin 2 on mRNA expression of the hyaluronic acid synthase gene (Has2).
  • the hyaluronic acid production promoter of the present invention is characterized in that lipocalin 2 and / or lipocalin 2 degradation product obtained by degrading lipocalin 2 with a proteolytic enzyme is an active ingredient.
  • the lipocalin 2 of the present invention can be used from any origin.
  • the lipocalin 2 derived from human and bovine has already been clarified in gene sequence and can be produced by gene recombination, but in the present invention, lipocalin 2 produced by genetic engineering techniques can also be used.
  • cells derived from the cell culture medium can also be used. Lipocalin 2 is contained in bovine colostrum and may be recovered from milk.
  • the lipocalin 2 degradation product is a lipocalin 2 purified by an arbitrary method so as to have a molecular weight of 8,000 or less with a protease such as trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, and V8 protease. It is possible to use limited peptide mixtures. However, the lower limit of the molecular weight is preferably 300 or more.
  • the hyaluronic acid production promoter of the present invention exhibits hyaluronic acid production promoting effect by oral administration or application.
  • the active ingredient lipocalin 2 or lipocalin 2 degradation product can be used as it is, but according to conventional methods, powders, granules, tablets, capsules It can also be used in the form of pharmaceutical preparations, drink preparations and the like.
  • oral preparations such as powders, granules, tablets and capsules are formulated by conventional methods using excipients such as starch, lactose, sucrose, mannitol, carboxymethylcellulose, 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 used as appropriate in addition to the excipient.
  • the binder include starch, dextrin, gum arabic, gelatin, hydroxypropyl starch, sodium carboxymethylcellulose, methylcellulose, crystalline cellulose, ethylcellulose, and polyvinylpyrrolidone.
  • the disintegrant include starch, hydroxypropyl starch. Carboxymethyl cellulose, sodium carboxymethyl cellulose, sodium carboxymethyl cellulose, crystalline cellulose and the like.
  • lipocalin 2 and lipocalin 2 degradation products can be blended in supplements, nutrients, foods and drinks, etc. as they are or after preparation. Since lipocalin 2 or a lipocalin 2 degradation product is relatively stable to heat, it is possible to heat sterilize the raw material containing the lipocalin 2 or the lipocalin 2 degradation product under conditions that are usually performed.
  • various dosage forms such as liquids, solids, semisolids, etc. are prepared by blending with commonly known components according to the purpose of use.
  • Preferred compositions include ointments, gels, creams, sprays, patches, lotions, powders and the like.
  • the hyaluronic acid production promoter of the present invention is a hydrocarbon such as petrolatum, higher fatty acid lower alkyl esters such as stearyl alcohol, isopropyl myristate, animal fats such as lanolin, polyhydric alcohols such as glycerin, glycerin fatty acid esters, mono Cosmetics for promoting hyaluronic acid production by mixing with surfactants such as stearic acid and polyethylene glycol, inorganic salts, waxes, resins, water and, if necessary, preservatives such as methyl paraoxybenzoate and butyl paraoxybenzoate And can produce medicines.
  • surfactants such as stearic acid and polyethylene glycol
  • inorganic salts such as stearic acid and polyethylene glycol
  • waxes such as stearic acid and polyethylene glycol
  • preservatives such as methyl paraoxybenzoate and butyl paraoxybenzoate And can produce medicines.
  • the effective amount of the hyaluronic acid production promoter of the present invention by oral administration is appropriately defined by the formulation form, administration method, purpose of use, and age, weight, and medical condition of the patient to which it is applied.
  • lipocalin 2 and / or lipocalin 2 degradation products exhibit hyaluronic acid production promoting action when ingested at least 10 ⁇ g per kg of rat body weight. Therefore, according to the extrapolation method, ingestion of 10 ⁇ g or more of lipocalin 2 and / or lipocalin 2 degradation product per adult per day can be expected to promote hyaluronic acid production.
  • Or may be administered as a medicine. The administration can be divided into several times a day as necessary.
  • the effective amount by application of the hyaluronic acid production promoter of the present invention varies depending on the dosage form, but is preferably 0.001 to 2% by weight based on the total amount of the composition to be applied. What is necessary is just to mix
  • a column packed with 3,000 g of S Sepharose cake is thoroughly washed with deionized water, passed through 10,000 L of skimmed milk, washed thoroughly with deionized water, and then a straight line of 0.1 to 1.0 M sodium chloride. Elute with a gradient. Thereafter, the eluted fraction containing lipocalin 2 was fractionated again by phenyl S Sepharose hydrophobic column chromatography. Furthermore, this fraction was sequentially treated with C4 and C8 reverse phase chromatography and gel filtration chromatography using an HPLC system to obtain 2400 mg of lipocalin (fraction A). In addition, the lipocalin 2 obtained in this way can be used as a hyaluronic acid production promoter as it is.
  • Example 1 Fraction A 25 mg obtained in Example 1 was suspended in 100 ml of water, pancreatin was added to a final concentration of 1%, and enzyme treatment was performed at 37 ° C. for 5 minutes to 6 hours. And after heat-processing at 90 degreeC for 5 minute (s), the enzyme was deactivated, it lyophilized
  • the average molecular weight of the lipocalin 2 degradation product thus obtained was about 8,000 for B, about 500 for C, and about 300 for D.
  • fraction A obtained in Example 1 25 mg was suspended in 100 ml of water, pepsin was added so that the final concentration was 0.01%, the pH was adjusted to 2 to 3, and then 12 ° C at 37 ° C. After carrying out enzyme treatment for a time and adjusting the pH to 8, trypsin was added so that the final concentration was 0.01%, and the enzyme treatment was carried out at 37 ° C. for 12 hours. And after heat-processing at 90 degreeC for 5 minute (s) and deactivating an enzyme, it lyophilized
  • Example 1 The sample A obtained in Example 1 and the samples B to E obtained in Example 2 were examined for hyaluronic acid production promoting action by animal experiments using rats.
  • a 7-week-old Wistar male rat was obtained in the physiological saline-administered group (control group), the sample A obtained in Example 1 was administered in 10 ⁇ g per kg body weight of the rat (Group A-1), and in Example 1.
  • skin tissues (each 300 mg) collected immediately after sacrifice of the shaved rat on the day before the test were subjected to measurement.
  • Example 2 Experiments using sample A obtained in Example 1 and samples B, C, and D obtained in Example 2 using a normal human fibroblast cell line [CCD45SK (ATCCRL 1506) collected from white female skin] The hyaluronic acid production promoting effect was examined by the above. Using a modified Eagle's medium (MEM, 10-101, manufactured by Dainippon Pharmaceutical Co., Ltd.) containing 10% by volume fetal bovine serum (hereinafter abbreviated as FBS), 4 ⁇ 10 4 normal human fibroblast cell lines / well / 0 After seeding in a 24-well plate so as to be 4 ml and culturing at 37 ° C.
  • MEM modified Eagle's medium
  • FBS fetal bovine serum
  • hyaluronic acid production in the group to which lipocalin 2 and / or lipocalin 2 degradation product was added was more than twice that of the group to which lipocalin 2 and / or lipocalin 2 degradation product was not added (control). It showed the ability to promote. This reveals that lipocalin 2 and / or lipocalin 2 degradation products have an action of acting on dermal fibroblasts and promoting hyaluronic acid production, and are shown to be useful as hyaluronic acid production promoters. It was.
  • the amount of hyaluronic acid in the culture solution thus obtained was measured with a hyaluronic acid measurement kit QnE Hyaluronic Acid (HA) Quantitative ELISA assay (manufactured by Biotech Trading Partners). The result is shown in FIG.
  • lipocalin 2 promotes hyaluronic acid production in the sample to which NGAL was added as compared with the control because the amount of hyaluronic acid was significantly increased.
  • RNA expression of the hyaluronic acid synthase gene was examined using a real-time PCR method. Specifically, NHDF (NB) cells were seeded in a 24-well plate at 0.5 ⁇ 10 5 cells / well, and were placed in a MEDIUM 106 medium (GIBCO) at 37 ° C. in a 5% CO 2 environment. For 3 days. After 3 days of culture period, NGAL dissolved in MEDIUM106 medium to 10 nM was added to and retained in cells for 2 hours, 4 hours, 6 hours, 9 hours, 12 hours and 24 hours, respectively. Total RNA was recovered by the procedure described above and cDNA was synthesized.
  • RNA extractant 0.5 ml of ISOGEN (manufactured by Nippon Gene) as an RNA extractant was added to the cultured cells and allowed to stand for 5 minutes, and then the cell solution solubilized by pipetting was collected in a 1.5 ml tube. After 0.1 ml of chloroform was added to the cell solution and stirred sufficiently, the upper layer (aqueous layer) separated into two layers was collected in a new 1.5 ml tube. 0.25 ml of 2-propyl alcohol was added to the recovered solution, left standing for 10 minutes, and then centrifuged at 15,000 rpm and 4 ° C. for 15 minutes to obtain a total RNA precipitate. The obtained precipitate was washed with 70% ethanol and then dissolved in DEPC water to obtain an RNA solution.
  • ISOGEN manufactured by Nippon Gene
  • CDNA was synthesized from 1 ⁇ g of RNA using Takara PrimeScript TM RT reagent Kit.
  • Real-time PCR using SYBR Green (Takara SYBR Prime Ex TaqII) was performed using the obtained cDNA as a template.
  • the reaction conditions were 95 ° C., 30 seconds of initial denaturation, 95 ° C., 5 seconds of denaturation, 57 ° C., 15 seconds of annealing, 72 ° C., 20 seconds of extension, for a total of 40 cycles.
  • Primers for confirming Has2 gene expression shown in Table 3 were used as primers. The results are shown in FIG.
  • Beverages for promoting hyaluronic acid production with the formulation shown in Table 4 were produced by conventional methods.
  • the flavor of the produced beverage was good and there were no problems such as precipitation.
  • a dough having the composition shown in Table 5 was produced by a conventional method, molded, and then baked to produce hyaluronic acid production promoting biscuits.
  • the hyaluronic acid production promoter having the composition shown in Table 6 was produced by a conventional method.
  • a lotion having the composition shown in Table 7 was produced by a conventional method.
  • a cream having the composition shown in Table 8 was produced by a conventional method.
  • Example 5 Using the lotion obtained in Example 6 and the cream obtained in Example 7, an actual use test was conducted.
  • a comparative product the same formulation as in Examples 6 and 7 was used except that lipocalin 2 and / or lipocalin 2 degradation product was excluded.
  • the skin lotion of the present invention has a significant improvement in dry feeling and rough skin compared with the skin lotion of the comparative product, and is excellent in hyaluronic acid production promoting effect. It was.
  • the cream of the present invention also has an improvement in dry feeling and a marked improvement in rough skin, as compared with the comparative cream, and has been found to have an effect of suppressing natural deterioration such as rough skin.
  • Test Example 6 For 20 patients with mild pain due to osteoarthritis, 100 g of the beverage of Example 3 was drunk once a day, and a one-year clinical trial was conducted. Assess joint pain and function with visual analog scale (VAS) for pain and with the Western Ontario and McMaster Universities (WOMAC) index for pain, function and stiffness in arthritic joints It was. The results are shown in Table 10.
  • the present invention relates to a hyaluronic acid production promoter, a hyaluronic acid production promoting supplement, a food and drink, and a hyaluronic acid production promoting cosmetic useful for preventing rough skin, wrinkles, reduced elasticity, reduced joint function, and the like.

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Abstract

La présente invention concerne l'utilisation d'une protéine de la famille de la lipocaline et/ou un produit protéolytique de la famille de la lipocaline, obtenu en utilisant une protéase comme la pepsine ou la pancréatine pour décomposer une protéine de la famille de la lipocaline, comme ingrédient actif dans un promoteur de production d'acide hyaluronique, un promoteur de production de collagène, une boisson/un aliment, et un produit cosmétique activant la production de collagène. Cette protéine de la famille de la lipocaline et/ou ce produit protéolytique de la famille de la lipocaline a un effet d'augmentation de la quantité d'acide hyaluronique.
PCT/JP2014/066000 2013-06-17 2014-06-17 Promoteur de production d'acide hyaluronique WO2014203883A1 (fr)

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JP2013126446A JP6259208B2 (ja) 2013-06-17 2013-06-17 ヒアルロン酸産生促進剤

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