EP4288063A1 - Composition pour lutter contre le stress oxydatif et/ou le prévenir comprenant au moins de la s-adénosyl méthionine et de l'astragalus sp. polysaccharides - Google Patents

Composition pour lutter contre le stress oxydatif et/ou le prévenir comprenant au moins de la s-adénosyl méthionine et de l'astragalus sp. polysaccharides

Info

Publication number
EP4288063A1
EP4288063A1 EP21710563.4A EP21710563A EP4288063A1 EP 4288063 A1 EP4288063 A1 EP 4288063A1 EP 21710563 A EP21710563 A EP 21710563A EP 4288063 A1 EP4288063 A1 EP 4288063A1
Authority
EP
European Patent Office
Prior art keywords
composition according
composition
oxidative stress
astragalus
gssg
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
EP21710563.4A
Other languages
German (de)
English (en)
Inventor
Michel Frey
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.)
Idec Therapeutic
Original Assignee
Idec Therapeutic
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 Idec Therapeutic filed Critical Idec Therapeutic
Publication of EP4288063A1 publication Critical patent/EP4288063A1/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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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

  • Composition for controlling and/or preventing oxidative stress comprising at least S-adenosyl methionine and Astragalus sp. polysaccharides
  • the invention relates to the field of compositions intended for controlling and/or preventing oxidative stress, particularly in a human being.
  • a composition comprising at least S-adenosyl methionine and Astragalus sp. polysaccharides, can be used as a food supplement or as a composition for topical application such as a cosmetic and/or dermatological and/or pharmaceutical cream or gel.
  • Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species (ROS) and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damages.
  • ROS reactive oxygen species
  • Oxidative stress from oxidative metabolism causes basal damage, as well as strand breaks in DNA.
  • US2015133370 relates to dietary compositions comprising reduced level of methionine, tryptophan, all amino acids, or protein, dietary compositions comprising glycerol as a substitute for monosaccharides, disaccharides, and polysaccharides to protect subjects against chemotherapy, radiotherapy, oxidative stress, or aging.
  • Glutathione is a tripeptide (cysteine, glycine, and glutamic acid) found in relatively high concentrations in many bodily tissues. It plays a pivotal role in reducing oxidative stress, maintaining redox balance, enhancing metabolic detoxification, and regulating the immune system and associated functions.
  • Various chronic, age-related diseases such as those related to neurodegenerative disorders, mitochondrial dysfunctions and correlated diseases, and even cancer, have been related to suboptimal/subfunctional or deficient glutathione levels.
  • POPs persistent organic pollutants
  • One usual confounding factor is the complexity of antioxidants or the situation in which antioxidants can possess prooxidant activity causing a hormetic effect enabling the body to bolster its endogenous antioxidant defenses.
  • the present invention is based on the work done by the inventor to established reference ranges for GSH/GSSG ratio as a biomarker of healthy conditions to limit early subclinical steps of chronic disease risks.
  • Another biomarker deemed clinically useful is serum y-glutamyltransferase (GGT) that is primarily involved in the metabolism of extracellular reduced glutathione, could be also used to follow the redox status of people.
  • GTT serum y-glutamyltransferase
  • the invention is also based on the assumption made by the inventor that the best option to follow the redox status of tissues is the calculation of the ratio between the 2 forms of glutathione i.e. free form to control oxidative (GSSG, after blocking stress redox) and reduced (i.e. free) form (GSH).
  • the ratio between each chemical status shifts the variability known in individuals and provide the functional activity and physiological equilibrium.
  • glutathione With up-reguiated oxidative stress in daily life, aging, subclinical and clinical diseases, malnutrition or increased toxic burden due to exposure to environmental pollutants, there can be even greater need for glutathione functions. While there may be a need to maintain high levels of glutathione, balancing the ratio between GSH and GSSG is required. In cancer, glutathione may need monitoring in patients undergoing chemotherapy due to the potential to support chemoresistance.
  • Astragalus Polysacharides (hereafter also APS) showed already antioxidative activities in scavenging models (superoxide anion radical-scavenging activity and hydroxyl radical-scavenging activity (Li Rui et al, 2010, Carbohydrates Polymers) but have been never described to provide activity on glutathione metabolism and GSH/GSSG balance.
  • the present invention shows that a composition comprising at least APS and S- adenosyl methionine (hereafter SAMe) can control and/or prevent oxidative stress in rebalancing the ratio between GSH and GSSG.
  • SAMe S- adenosyl methionine
  • the present invention regards to a composition for controlling and/or preventing oxidative stress comprising at least: S-Adenosyl-methionine and Astragalus sp. polysaccharides (titred 20%, extract).
  • the invention is a composition for optimizing GSH/GSSG blood serum ratio, above or equal to 10, preferentially above or equal to 15, comprising at least: S-Adenosyl-methionine and Astragalus sp. polysaccharides (titred 20%, extract).
  • the composition comprises at least a vitamin chosen from vitamins in the B group.
  • the at least vitamin in the B group is selected from vitamins B6, B9, B12 or a mixture thereof.
  • Astragalus sp. is Astragalus membranaceus polysaccharides.
  • the composition also comprises a magnesium salt.
  • the said composition also comprises vitamin D.
  • the composition of the present invention is intended for a daily oral intake and comprises at least:
  • the composition is used as a diet supplement.
  • the composition is in the form of a solid mixture able to be introduced an oral support such as in a capsule, a pill, a tablet or in the form of a mixture able to be introduced in a liquid form.
  • the invention is relating to the composition according to the invention for controlling and/or protecting a human or an animal from oxidative stress.
  • This use of the composition is comprising the steps of:
  • Controlling the GSH/GSSG blood serum ratio is above or equal to 10, preferably above or equal to 15, preferentially above 30,
  • said composition is intended for a daily intake of 2 or 3 capsules or tablets or pills.
  • the invention also provides a method for controlling and/or protecting a human or an animal from oxidative stress comprising:
  • Controlling the GSH/GSSG blood serum ratio is above or equal to 10, preferably above or equal to 15; preferentially above 30.
  • the administration of a composition according to the instant invention is a daily intake of 2 or 3 capsules or tablets or pills as described above.
  • the invention provides a composition for topical application such as a cosmetic and/or dermatological and/or pharmaceutical cream or gel.
  • the instant invention encompasses a process for diagnosing aging, in particular linked to environmental stress, based on the oxidative stress in a human or in an animal comprising:
  • Figurel depicts the Time-related effects of the treatment, according to the composition claimed herein, on the ratio GSH/GSSG in blood. - Increase of the ratio means higher global ant/oxydative activity (AOX).
  • This figure 2 shows the Efficacy of a treatment, according to the composition claimed herein, on the ratio GSH/GSSG in blood.
  • Descriptive statistical analysis by box-plot tool depicts the group of numerical data by each volunteer. This analysis has lines extending from the boxes indicating variability outside the upper and lower quartiles. Box-plot are no parametric, they display variations in samples of a statistical population.
  • This figure shows the efficacy of a treatment, according to the composition used in example 2, on the ratio GSH/GSSG in blood - global analysis of data in human study -
  • Figure 3 represents the Sex-dependant analysis of the effects of a mix according to the composition claimed herein, on the ratio GH/GSSG.
  • the invention aims to propose a composition able to control and/or preventthe oxidative stress, comprising at least S-Adenosyl-methionine and Astragalus sp. Polysaccharides.
  • the instant invention aims to provide a composition for optimizing GSH/GSSG blood serum ratio, above or equal to 10, preferably above or equal to 15, preferentially above 30.
  • a composition comprising at least: S-Adenosyl- methionine and Astragalus sp. polysaccharides (titred 20%, extract)
  • said composition as describes above comprises in addition a vitamin chosen from vitamins in the B group.
  • SAMe S-adenosylmethionine
  • SAMe is the principai methyl donor and the precursor of aminopropyl groups and of glutathione in the liver; it also regulates the activities of various enzymes.
  • SAMe is formed by activation of dietary methionine by ATP in a reaction catalyzed by methionine adenosyltransferase (EC 2.5.1 .6).
  • SAMe contains a high-energy sulfonium ion, which activates each of the attached carbons toward nucleophilic attack and confers on SAMe the ability to participate in 3 major types of reactions: transmethylation, transsulfuration, and aminopropylation.
  • Astragalus membranaceus (essentially roots) is a type of traditional Chinese medicine with a long history of clinical application. It is used in the improvement and treatment of various diseases as medicine and diet to decrease the spleen and improve the qi.
  • the main component of Astragalus membranaceus preferably the roots, is the polysaccharide fraction (APS for Astragalus Potysachar/des), which possesses multiple pharmacological properties.
  • APS known activities are 1 ) immune regulation ie proliferation of immune ceils, release of cytokines, and secretion of immunoglobulin, 2) anti-aging, 3) anti-tumor by enhancing immunity and apoptosis of tumor cells, inhibiting the proliferation and transfer of tumor cells, 4) antiviral effects, 5) regulation of blood glucose such as type I diabetes mellitus, type II diabetes mellitus and diabetic complications, 6) lipid-lowering, 7) anti-fibrosis, 8) antimicrobial activities and antioxidants activities notably.
  • GSH/GSSG anti-oxidative ratio
  • a liquid or solid food supplement and a cosmetic or dermatological composition can be characterized in that it comprises the composition described above.
  • said composition as describes above comprises in addition a vitamin chosen from vitamins in the B group.
  • a vitamin chosen in B group means all the group B vitamins and in particular vitamins: B1 , B2, B3, B5, B6, B8, B9, B12, their respective precursors, or a mixture of vitamins and/or respective precursors.
  • said vitamin is B6, B9 or B12, their respective precursors, alone or a mixture thereof or a mixture of said vitamins and/or respective precursors.
  • Vitamin B6 promotes particularly the absorption of magnesium and the synthesis of serotonin (an essential neurotransmitter).
  • Vitamin B9 or folic acid has the property of also acting on the metabolism of amino acids and the synthesis of proteins; it participates in the renewal of immune cells, in the formation of red corpuscles and in the supply of oxygen needed by the organism.
  • Vitamin B12 is essential to the correct functioning of the central and peripheral nervous systems.
  • Vitamin D is added in the composition of the invention alone or mixed with other vitamins.
  • said composition comprises a magnesium salt.
  • Magnnesium salt means any salt comprising magnesium and being biologically tolerated by the human body. The following can be cited as an example: magnesium chloride, magnesium citrate, magnesium gluconate, magnesium carbonate, magnesium pidolate, magnesium lactate, magnesium aspartate, magnesium sulphate, magnesium hydroxide, magnesium oxide, magnesium bisglycinate and magnesium glycerophosphate.
  • the choice of the type of magnesium salt can be made according to the elementary magnesium content or according to the bioavailability and solubility of the magnesium salt.
  • said magnesium salt chosen for implementing the invention is magnesium oxide or magnesium glycerophosphate; preferably said magnesium salt is of marine origin.
  • said composition is in the form suitabie for topical administration.
  • topical composition is in a form of oil in water or water in oil emulsions, an aqueous or oily gel, or any liquid or semi-liquid topical form.
  • Topical administration means any administration by local method, for example on the skin, an orifice or mucosa.
  • Topical administration as used here, comprises the cutaneous, auricular, nasal, vaginal, urethral and rectal routes.
  • the composition is dermatological acceptable composition.
  • Dermatologically acceptable composition means all compositions intended to be administered topically and respectful of the physical and chemical integrity of the skin and mucosa, such as so-called cosmetic, dermatological or pharmaceutical compositions.
  • said composition is preferably in the form of a gel or an emulsion, preferably having properties of resistance to oxidation by the incorporation in the composition of antioxidants such as extracts of acai berry, pecan nut, hazelnut, prune, mulberry, pomegranate, strawberry, kiwi fruit, date, fig, garlic, almond, broccoli, beetroot, eggplant or any other known molecule having the property of limiting oxidative stress such as resveratrol, quercetin or any of its derivatives alone or mixed, vitamin E or vitamin C.
  • antioxidants such as extracts of acai berry, pecan nut, hazelnut, prune, mulberry, pomegranate, strawberry, kiwi fruit, date, fig, garlic, almond, broccoli, beetroot, eggplant or any other known molecule having the property of limiting oxidative stress such as resveratrol, quercetin or any of its derivatives alone or mixed, vitamin E or vitamin C.
  • an essential oil will preferably be chosen, for example essential oil of helichrysum italicum to promote microcirculation, essential oil of Aniba parviflora for firming skin tissues, essential oil of Citrus limon, for its blood-fluidising power, essential oil of Wintergreen for its vasodilatory action, essential oil of Lavandula officinalis for its healing and fluidising action, essential oil of Mentha piperita for its antipruritic power, essential oil of ravinsara for its skin energising action, essential oil of Melaleuca alternifolia for its skin antibacterial activity or essential oil of Pelagonium asperum for its “anti-wrinkle” power.
  • the composition may be in the form of a liquid such as a syrup or a drinkable suspension, or in the form of a solid such as a tablet, a pill or a capsule.
  • the solid form is acid-resistant, in order to ensure disintegration of the constituents for assimilation thereof by the body, at the intestinal and non-gastric level.
  • said composition according to the invention for ora! administration comprises at least: between 50 mg and 1000 mg, S-Adenosyl-methionine, between 20 mg and 1000 mg Astragalus sp. polysaccharides, optionally between 1 mg and 50 mg magnesium salt.
  • composition according to the invention comprises at least for a daily intake:
  • the daily intake is administrated in 2 or 3 capsules or tablets or pills per day.
  • composition according to the invention may preferably contain at least from 0,5% to 20% by weight S- Adenosyl-methionine, more preferentially at least from 1 % to 10% by weight S- Adenosyl-methionine.
  • Another subject matter of the invention is a food supplement for human or animal (preferably domestic pets), liquid or solid, comprising a composition according to the invention.
  • a method for, or a process for controlling and/or protecting a human or an animal from oxidative stress comprising:
  • a composition as described previously to a human or an animal in need thereof, preferentially once daily and more preferred for a determined duration.
  • Said duration is at least 2 weeks, better between 3 weeks and several months and even better between 4 weeks (1 month) and 12 weeks (3 months).
  • the GSH/GSSG blood serum ratio is above or equal to 10, preferably above or equal to 15, preferentially above 30.
  • invention encompasses also a process for diagnosing aging in particular linked to environmental stress based on the oxidative stress, in a human or in an animal comprising:
  • the GSH/GSSG blood serum ratio rebalance is the way for controlling and/or preventing said oxidative stress or aging.
  • invention provides a process for diagnosing aging and oxidative stress as well as method (or process) for controlling and/or preventing said oxidative stress in rebalancing GSH/GSSG blood serum ratio.
  • Example 1 example of compositions in the scope of invention
  • Magnesium/marine salt from about 50mg to 300mg, preferably between 100mg and 200 mg
  • - Vit B6 (Piridoxine chlor. 82%): from about 0,1 mg to 5mg preferably between 1 mg and 3mg
  • compositions as described above are included in vegetal caps HPMC
  • Example 2 clinical trial in human volunteers after 2 months treatment This example is clinical results in human volunteers after 2 months treatment with a mix of SAMe (500 mg per day) and Astragalus membranaceus polysaccharides (20% titred extract (400mg per day)) Table 1 :
  • This example provides individual data as depicted in Figure 1 and shows the benefits of a composition according to the invention regarding the prevention of oxidative stress. It shows particularly that after treatment according to example 1 , the balance ratio is favorably in favor of GSH rate. These results show that after treatment, GSH/GSSG blood serum ratio is at least above or equal to 10 and preferentially above or equal to 15, preferentially above 30.
  • a treatment according to the invention provides an Increase of the ratio means protective AOX activity induced by the mix treatment.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Birds (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compositions destinées à lutter contre le stress oxydatif et/ou à le prévenir, en particulier chez un être humain, par l'optimisation du rapport sérique du sang GSH/GSSG. Une telle composition comprenant au moins de la S-adénosyl méthionine et de l'Astragalus sp. polysaccharides peut être utilisée en tant que complément alimentaire ou en tant que composition en vue d'une application topique telle qu'une crème ou un gel cosmétique et/ou dermatologique et/ou pharmaceutique.
EP21710563.4A 2021-02-05 2021-02-05 Composition pour lutter contre le stress oxydatif et/ou le prévenir comprenant au moins de la s-adénosyl méthionine et de l'astragalus sp. polysaccharides Pending EP4288063A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2021/000049 WO2022167827A1 (fr) 2021-02-05 2021-02-05 Composition pour lutter contre le stress oxydatif et/ou le prévenir comprenant au moins de la s-adénosyl méthionine et de l'astragalus sp. polysaccharides

Publications (1)

Publication Number Publication Date
EP4288063A1 true EP4288063A1 (fr) 2023-12-13

Family

ID=74860332

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21710563.4A Pending EP4288063A1 (fr) 2021-02-05 2021-02-05 Composition pour lutter contre le stress oxydatif et/ou le prévenir comprenant au moins de la s-adénosyl méthionine et de l'astragalus sp. polysaccharides

Country Status (2)

Country Link
EP (1) EP4288063A1 (fr)
WO (1) WO2022167827A1 (fr)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8865646B2 (en) 2007-03-28 2014-10-21 University Of South California Dietary compositions and methods for protection against chemotherapy, radiotherapy, oxidative stress, and aging
US11268964B2 (en) * 2014-11-11 2022-03-08 The Johns Hopkins University Biomarkers useful in the treatment of subjects having diseases of the eye
FR3029418B1 (fr) * 2014-12-09 2018-03-09 Michel Frey Composition destinee a ralentir les signes du vieillissement pathologique ou physiologique.
KR20200144747A (ko) * 2019-06-19 2020-12-30 대한민국(농촌진흥청장) 황기 추출물을 유효성분으로 포함하는 신경세포 보호용 조성물

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WO2022167827A1 (fr) 2022-08-11

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