EP4225262A1 - Hydrolysat de collagène utilisé en tant que substance active pour retarder le vieillissement - Google Patents

Hydrolysat de collagène utilisé en tant que substance active pour retarder le vieillissement

Info

Publication number
EP4225262A1
EP4225262A1 EP21749540.7A EP21749540A EP4225262A1 EP 4225262 A1 EP4225262 A1 EP 4225262A1 EP 21749540 A EP21749540 A EP 21749540A EP 4225262 A1 EP4225262 A1 EP 4225262A1
Authority
EP
European Patent Office
Prior art keywords
collagen hydrolyzate
use according
collagen
hydrolyzate
administered
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
EP21749540.7A
Other languages
German (de)
English (en)
Inventor
Stephan Hausmanns
Hans-Ulrich Frech
Steffen Oesser
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gelita AG
Original Assignee
Gelita AG
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 Gelita AG filed Critical Gelita AG
Publication of EP4225262A1 publication Critical patent/EP4225262A1/fr
Pending legal-status Critical Current

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
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
    • A61K38/014—Hydrolysed proteins; Derivatives thereof from animals from connective tissue peptides, e.g. gelatin, collagen
    • 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
    • A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
    • 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
    • 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
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/92—Oral administration

Definitions

  • Collagen hydrolyzate as an active ingredient to delay aging
  • the present invention relates to collagen hydrolyzate for use as an agent to delay aging of body cells in humans or animals.
  • the biological aging of the human or animal body is related to external environmental influences that accumulate over a lifetime. Regardless of such environmental influences, there is also a general connection between aging and a gradual shortening of the telomeres during life at the level of the individual body cells. Telomeres are repetitive sections of DNA at the ends of the chromosomes that initially become shorter with each cell division.
  • telomere length falls below a certain point, no further cell divisions take place.
  • the original length of the telomeres is less relevant than the telomere shortening rate, which can be specified, for example, as the average shortening of the telomeres in base pairs per year of life (see K. Whittemore et al. in PNAS 116 (2019) 15122-15127).
  • the invention is based on the object of proposing an effective active substance for delaying the aging of body cells in humans or animals.
  • collagen hydrolyzate as the corresponding active substance is proposed according to the present invention.
  • Cell experiments have shown that collagen hydrolyzate significantly counteracts the shortening of telomeres and activates telomerase, as detailed below.
  • the invention relates to the use of collagen hydrolyzate to delay skin aging. This typically manifests itself in the form of wrinkling, loss of elasticity, formation of so-called age spots, etc.
  • the body cells affected by the action of the collagen hydrolyzate are fibroblasts.
  • body cells whose aging can be delayed within the scope of the invention are other connective tissue cells such as osteoblasts and chondrocytes, as well as muscle cells (myocytes), nerve cells (neurons) and cells of the immune system.
  • connective tissue cells such as osteoblasts and chondrocytes
  • muscle cells myocytes
  • nerve cells nerve cells
  • the use of collagen hydrolyzate is a non-therapeutic use, ie in particular a cosmetic use. This takes into account the fact that the biological aging of the body as a natural process is not a pathological condition that would require therapy in the medical sense. Nevertheless, delaying aging can contribute to an improvement in the quality of life.
  • the use of the collagen hydrolyzate is a therapeutic use for the prevention and/or treatment of age-related diseases.
  • diseases which are associated with a shortening of the telomeres, are in particular atherosclerosis, chronic liver diseases, chronic inflammatory bowel diseases and certain diseases of the adrenal gland and the spleen.
  • Other diseases that occur more frequently with increasing age are osteoporosis, arthrosis, sarcopenia and dementia diseases such as Alzheimer's.
  • the collagen hydrolyzate When used according to the invention, the collagen hydrolyzate preferably counteracts the shortening of telomeres in the body cells, and in particular it reduces the rate of telomere shortening. As already mentioned, the rate of telomere shortening correlates with life expectancy, at least when comparing between different species. A reduction in this rate by collagen hydrolyzate could be explicitly shown in the cell experiments carried out with human fibroblasts.
  • the collagen hydrolyzate can activate the enzyme telomerase in the body cells. This effect could also be shown in the cell experiments with human fibroblasts. However, telomerase activation is not necessarily the only mechanism of action to counteract telomere shortening.
  • collagen hydrolyzate has long been known to have positive physiological effects, particularly in connection with osteoporosis or joint problems. However, there was no evidence whatsoever of an interaction of collagen hydrolyzate with the telomeres, so that the effectiveness observed within the scope of the present invention is quite surprising.
  • the collagen hydrolyzate can be administered within the scope of the present invention as a dietary supplement or as a medicinal product. In any case, collagen hydrolyzate is a product that is completely harmless to health and has no known harmful side effects.
  • the collagen hydrolyzate is preferably administered orally. It is known that the peptides of the collagen hydrolyzate are resorbed in the intestine, at least to a certain extent, even with relatively high molecular weights of up to 10,000 Da. Orally administered collagen hydrolyzate can therefore in principle reach all body cells as the site of action.
  • the specific dosage form of the collagen hydrolyzate can be that of a powder, a solution, a gel, a tablet or a capsule.
  • the daily dose of the administered collagen hydrolyzate is advantageously from about 0.5 to about 20 g, preferably from about 2 to about 15 g, more preferably from about 3 to about 10 g, in particular in a daily dose of approx. 4 to approx. 8 g.
  • the collagen hydrolyzate as the active ingredient according to the invention typically has an average molecular weight of 500 to 15,000 Da, preferably 1000 to 8000 Da, more preferably 1500 to 5000 Da, most preferably 1800 to 2200 Da. This information always means the weight-average molecular weight, which can be determined in particular by gel permeation chromatography.
  • the collagen hydrolyzate is preferably produced by enzymatic hydrolysis of a collagen-containing starting material.
  • endopeptidases or exopeptidases of microbial or plant origin are used for this hydrolysis.
  • collagen hydrolyzates can be produced in the molecular weight range desired in each case.
  • the collagen-containing starting material is usually selected from the skin or bones of vertebrates, preferably mammals or birds, and in particular from the skin of cattle or pigs (beef split or pork rind).
  • the starting material containing collagen can be selected from the skin, bones and/or scales of fish, in particular cold or warm water fish.
  • collagen hydrolyzate can also be obtained as starting material from invertebrates and used in the context of the present invention.
  • collagen hydrolysates can be produced from molluscs or from jellyfish.
  • the collagen hydrolyzate can either be prepared from these starting materials in a one-step process or via the intermediate gelatine stage, in which case both type A and type B gelatine can be used.
  • the collagen hydrolyzate is preferably produced by the successive action of at least two endoproteases with a different specificity, in particular of at least two different metalloproteases and/or serine proteases, i.e. proteases which cleave the amino acid sequence of the collagen molecules in front of or behind specific amino acids.
  • the metalloproteases and/or serine proteases are favorably enzymes from the microorganisms Bacillus subtilis, Bacillus licheniformis, Bacillus amyloliquefaciens, Aspergillus oryzae and Aspergillus melleus.
  • endoproteases not only can a certain molecular weight distribution of the collagen hydrolyzate be obtained, but It also influences the nature of the amino acids at the termini of the peptides contained in the hydrolyzate. In this respect it is preferred, for example, if at least 50% of the N-terminal amino acids of the collagen hydrolyzate are hydrophobic amino acids, in particular alanine, leucine and isoleucine.
  • the collagen hydrolyzate can be produced within the scope of the invention by recombinant gene expression.
  • natural collagen sequences in particular from cattle or pigs, and expressing them in genetically modified cells (e.g. yeast, bacteria or plant cells, in particular tobacco)
  • genetically modified cells e.g. yeast, bacteria or plant cells, in particular tobacco
  • products can be produced which are essentially identical to the hydrolysis products of the corresponding raw materials containing collagen. In this way it is possible to obtain a narrower or precisely specified molecular weight distribution.
  • the collagen hydrolyzate is administered in combination with at least one other active ingredient which counteracts a shortening of telomeres in the body cells.
  • at least one other active ingredient which counteracts a shortening of telomeres in the body cells.
  • the at least one other active ingredient that counteracts a shortening of telomeres is preferably selected from plant extracts of plants of the genera Astralagus (tragacanth), Cimicifuga (silver cohosh), Dendropanax and Kappaphycus.
  • the collagen hydrolyzate is administered in a composition which, apart from the collagen hydrolyzate, contains no other active substances.
  • the administered composition essentially consists entirely of the collagen hydrolyzate. If the collagen hydrolyzate is not used as the sole active ingredient, according to a further embodiment of the invention it can be combined with one or more other components (eg in a dietary supplement or drug) which have a positive physiological effect.
  • Such components are preferably selected from vitamin C, vitamins from the B, D, E and K series, conjugated linolenic acids, caffeine and its derivatives, guarana extract, green tea extract, epigallocatechin gallate, creatine, L-carnitine, L-citrulline, L- Arginine, a-lipoic acid, N-acetylcysteine, NADH, D-ribose, magnesium aspartate, antioxidants such as anthocyanins, carotenoids, flavonoids, resveratol, glutathione, superoxide dismutase and xanthans such as mangiferin, minerals such as iron, magnesium, calcium, zinc, selenium and phosphorus, and other proteins, hydrolyzates or peptides such as soy, wheat or whey protein.
  • the present invention further relates to a method for retarding the aging of body cells in humans or animals, comprising administering collagen hydrolyzate to a human or animal. Advantages and preferred embodiments of this method have already been described in connection with the collagen hydrolyzate according to the invention.
  • the collagen hydrolyzate (KH) used for the investigations is marketed by the applicant under the name VERSIOL®. It is produced by enzymatic hydrolysis of Type A pork skin gelatine and has an average molecular weight of approximately 2,000 Da.
  • collagen hydrolyzate The effects of collagen hydrolyzate were studied over a wide range of concentrations.
  • cell cultures were carried out (both under standard and oxidative conditions), in which the culture medium was mixed with 0.01 mg/ml, 0.1 mg/ml, 1 mg/ml or 10 mg/ml collagen hydrolyzate. Control batches were each without the addition of collagen hydrolyzate.
  • the cell cultures were maintained over a period of 8 weeks, with the population doubling (PD) per passage being determined weekly.
  • the cumulative PD is given in the following tables for standard conditions and for oxidative conditions:
  • Telomere lengths are determined using fluorescence in situ hybridization (FISH).
  • FISH fluorescence in situ hybridization
  • a fluorescence-labeled peptide nucleic acid probe is used, which hybridizes with three repetitive telomere sequences.
  • the fluorescence intensity of a given telomere is proportional to its length, quantitated using control cells of known telomere length.
  • telomere lengths were determined after 4 weeks and after 8 weeks, as well as for the control batch at the beginning of the cultivation (week 0).
  • the cells were fixed and disrupted with pepsin, with five cell disruptions being carried out per time point and cell culture.
  • the DNA was stained with 4',6-diamidine-2-phenylindole (DAPI) and hybridization of the telomeres was performed with the probe.
  • DAPI 4',6-diamidine-2-phenylindole
  • telomere lengths and their distribution were calculated with appropriate software and statistically analyzed using Student's t-test.
  • telomere length The median value of the telomere length, the 20th percentile (each in kilobase pairs, kbp) and the proportion of "short telomeres" (less than 3 kbp) were calculated for each cell culture after 4 weeks and after 8 weeks from the data obtained under the fluorescence microscope.
  • the results are shown in the following tables, with the p-values according to each also being given the t-test when the respective sample is compared with the corresponding sample of the control batch without collagen hydrolyzate. At values of p ⁇ 0.05, the difference to the control batch is statistically significant, these values are printed in bold.
  • the culture medium used was high-glucose DMEM (Dulbecco's Modified Eagle's Medium), supplemented with 10% fetal calf serum, 100 U/ml penicillin and 1,000 U/ml streptomycin.
  • the telomerase activity was determined at the beginning of the cultivation and after 24 hours.
  • the same collagen hydrolyzate was used as for determining the telomere lengths (see Section 1.2). This was added to the culture medium in an amount of 0.01 mg/ml, 0.1 mg/ml, 1 mg/ml or 10 mg/ml. In the control batch, no collagen hydrolyzate was added.
  • telomere activity is determined using the TRAP method (Telomeric Repeat Amplification Protocol).
  • TRAP method Telomeric Repeat Amplification Protocol
  • the cells are lysed and the proteins are extracted.
  • An oligonucleotide substrate is added, which is extended by the extracted telomerase according to the natural telomeres.
  • Telomerase reaction products are amplified by real-time quantitative PCT.
  • the number of cycles after which the fluorescence first rises above a threshold value (Ct value) is used as a measured variable.
  • the relative telomerase activity (RTA) of the sample can be calculated by calibrating using HeLa cells in different concentrations.
  • telomerase activity was determined in triplicate.
  • the mean values and standard deviations (SD) are given in the following table, as well as the p-values according to the t-test for the respective comparison with the control batch (without KH). A p-value of less than 0.05 indicates statistical significance.
  • Relative telomerase activity is given in the following table, as well as the p-values according to the t-test for the respective comparison with the control batch (without KH). A p-value of less than 0.05 indicates statistical significance.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Birds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Materials For Medical Uses (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un hydrolysat de collagène destiné à être utilisé en tant que substance active pour retarder le vieillissement de cellules du corps humain ou animal.
EP21749540.7A 2020-10-09 2021-07-13 Hydrolysat de collagène utilisé en tant que substance active pour retarder le vieillissement Pending EP4225262A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102020126594.8A DE102020126594A1 (de) 2020-10-09 2020-10-09 Kollagenhydrolysat als Wirkstoff zum Verzögern der Alterung
PCT/EP2021/069480 WO2022073664A1 (fr) 2020-10-09 2021-07-13 Hydrolysat de collagène utilisé en tant que substance active pour retarder le vieillissement

Publications (1)

Publication Number Publication Date
EP4225262A1 true EP4225262A1 (fr) 2023-08-16

Family

ID=77179974

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21749540.7A Pending EP4225262A1 (fr) 2020-10-09 2021-07-13 Hydrolysat de collagène utilisé en tant que substance active pour retarder le vieillissement

Country Status (11)

Country Link
US (1) US20230241154A1 (fr)
EP (1) EP4225262A1 (fr)
JP (1) JP2023544858A (fr)
KR (1) KR20230084171A (fr)
CN (1) CN116456999A (fr)
AU (1) AU2021356989A1 (fr)
BR (1) BR112023006118A2 (fr)
CA (1) CA3195119A1 (fr)
DE (1) DE102020126594A1 (fr)
MX (1) MX2023003920A (fr)
WO (1) WO2022073664A1 (fr)

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070122501A1 (en) 2003-06-27 2007-05-31 Hong Kong University Of Science And Technology Formulations containing astragalus extracts and uses thereof
KR101218898B1 (ko) * 2010-04-27 2013-01-07 샘표식품 주식회사 콜라겐 합성 촉진용 조성물
DE102010060564A1 (de) 2010-11-15 2012-05-16 Gelita Ag Verwendung von Kollagenhydrolysat zur Verbesserung der Gesundheit der menschlichen Haut, Haare und/oder Nägel
DE102012101911A1 (de) 2012-03-07 2013-09-12 Gelita Ag Verwendung von Kollagenhydrolysat
ITMI20122145A1 (it) 2012-12-14 2014-06-15 Velleja Res Srl Composizioni per uso orale contenenti idrolizzati di collagene, di elastina e vitamina c favorenti la deposizione di matrice extra-cellulare
DE202015102041U1 (de) * 2015-04-24 2016-04-26 Orthomol Pharmazeutische Vertriebs Gmbh Orale Zusammensetzung enthaltend Kollagenhydrolysat und Vitamin C
US20180207087A1 (en) 2017-01-25 2018-07-26 Youna Son Kit and aesthetic system for prevention of skin aging
DE102019202606A1 (de) 2018-11-06 2020-05-07 Gelita Ag Rekombinante Herstellung eines Kollagenpeptidpräparates und dessen Verwendung
CN109602668A (zh) * 2019-02-22 2019-04-12 浙江康知秀日用品有限公司 一种抗衰老抗皱组合物及其应用

Also Published As

Publication number Publication date
DE102020126594A1 (de) 2022-04-14
AU2021356989A9 (en) 2024-10-03
JP2023544858A (ja) 2023-10-25
WO2022073664A1 (fr) 2022-04-14
US20230241154A1 (en) 2023-08-03
MX2023003920A (es) 2023-04-24
BR112023006118A2 (pt) 2023-05-09
CA3195119A1 (fr) 2022-04-14
KR20230084171A (ko) 2023-06-12
CN116456999A (zh) 2023-07-18
AU2021356989A1 (en) 2023-05-18

Similar Documents

Publication Publication Date Title
DE69529873T2 (de) Knochenstärkendes Mittel, Lebensmittel und Getränke enthaltend dieses Mittel
EP0558727B1 (fr) Composition stimulant la croissance osseuse
EP0874618B1 (fr) Preparation pour stimuler la pousse des cheveux, ameliorer la structure de la peau et/ou regenerer les ongles
WO2020094728A1 (fr) Production par voie recombinante d'une préparation de peptides de collagène et utilisation de celle-ci
DE60003837T2 (de) Tetrapeptid, das die funktionelle aktivität von neuronen stimuliert, dieses enthaltendes pharmakologisches mittel und seine verwendung
EP3506929A1 (fr) Utilisation d'un hydrolysat de collagène pour améliorer la capacité d'endurance et stimuler le catabolisme lipidique
DE10251709A1 (de) Wirkstoffe zur Stimulierung der humanen beta-Defensine vom Typ 2 und/oder Typ 3 und kosmetische oder pharmazeutische Zusammensetzungen, die solche Wirkstoffe enthalten
DD290798A5 (de) Verwendung von bakterienlysierendem enzymprodukt und protease als zusatzstoff zur verbesserung der futterverwertung in der tierproduktion
US20230149490A1 (en) Novel composition comprising edelweiss-derived exosome as active ingredient
EP1908455A1 (fr) Préparation de soin pour les cheveux
DE69637104T2 (de) Heilmittel für arthrosis deformans und entzündliche gelenkerkrankungen
CN103547254B (zh) 含有来自胎盘的成分的皱纹改善用组合物
EP0552516B1 (fr) Extraits aqueux synthétiques d'organes
DE69733097T2 (de) Mittel zur Verbesserung der Knochenbildung und zur Inhibierung der Knochenresorption
CN109069588A (zh) 包含gdf11的组合物和其用途
WO2020128070A2 (fr) Hydrolysat de collagène destiné à être utilisé contre les maladies de la peau et les maladies des intestins
WO2022073664A1 (fr) Hydrolysat de collagène utilisé en tant que substance active pour retarder le vieillissement
KR20130114808A (ko) 콜라겐 천연 발효액을 포함하는 화장료 조성물
DE202006020459U1 (de) Zubereitung mit marinem Kollagen zur Proteinasehemmung
DE3543221C2 (de) Kosmetische Zusammensetzungen für die Kopfhaut und Haarbehandlungsverfahren
JPH0665041A (ja) 皮膚外用剤
DE102012101911A1 (de) Verwendung von Kollagenhydrolysat
EP4342448A1 (fr) Nouvelle composition comprenant un exosome dérivé d'iris en tant que principe actif
DE69424184T2 (de) Methode zur Herstellung von Peptidprodukten
KR102682938B1 (ko) 식물체로부터 pdrn 생산 방법

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20230320

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230907

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)