WO2020213616A1 - Composition servant à prévenir et/ou à traiter la maladie d'alzheimer et/ou la démence d'alzheimer, et composition servant à réduire la neurotoxicité de l'oligomère bêta-amyloïde - Google Patents

Composition servant à prévenir et/ou à traiter la maladie d'alzheimer et/ou la démence d'alzheimer, et composition servant à réduire la neurotoxicité de l'oligomère bêta-amyloïde Download PDF

Info

Publication number
WO2020213616A1
WO2020213616A1 PCT/JP2020/016483 JP2020016483W WO2020213616A1 WO 2020213616 A1 WO2020213616 A1 WO 2020213616A1 JP 2020016483 W JP2020016483 W JP 2020016483W WO 2020213616 A1 WO2020213616 A1 WO 2020213616A1
Authority
WO
WIPO (PCT)
Prior art keywords
tyrosol
composition
alzheimer
mice
treatment
Prior art date
Application number
PCT/JP2020/016483
Other languages
English (en)
Inventor
Wataru Araki
Jinwei Yang
Original Assignee
Wataru Araki
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
Priority claimed from JP2020068069A external-priority patent/JP7333626B2/ja
Application filed by Wataru Araki filed Critical Wataru Araki
Publication of WO2020213616A1 publication Critical patent/WO2020213616A1/fr

Links

Images

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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/41—Crassulaceae (Stonecrop family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention concerns the compositions that are useful for the prevention and treatment for Altzheimer’s disease and/or Alzheimer dementia (hereafter ”AD”) and those that effectively reduce the neurotoxicity for amyloid- ⁇ (hereafter “A ⁇ ”) oligomers.
  • AD Altzheimer’s disease and/or Alzheimer dementia
  • a ⁇ amyloid- ⁇
  • AD Alzheimer's disease
  • MCI mild cognitive impairment
  • AD amyloid cascade hypothesis
  • a ⁇ gradually forms soluble assemblies called A ⁇ oligomers (hereafter “A ⁇ O”) and then aggregates as fibrils and deposits as senile plaques in the brain.
  • a ⁇ O A ⁇ oligomers
  • the accumulation of A ⁇ provokes neuronal toxicities, such as abnormalities of microtubule-associated protein tau and synaptic disturbances, and also inflammatory responses, which leads to neurodegeneration and eventually the occurrence of dementia. It is also known that A ⁇ accumulation occurs at the stage of MCI due to AD.
  • AD Alzheimer's disease
  • Patent Document 1 described below discloses a method to block the production of A ⁇
  • Patent Document 2 described below discloses technologies relating to phenol derivatives that inhibit A ⁇ aggregation
  • Patent Document 3described below discloses technologies relating to specific antibodies to promote the removal of A ⁇ in the brain
  • Patent Document 1
  • Patent Document 2
  • a ⁇ O themselves induce neurotoxic effects; however no exact compounds have been reported that can reduce A ⁇ O neurotoxicity. If the A ⁇ O neurotoxicity can be reduced, such therapy will be helpful in achieving the prevention and treatment of AD together with the other therapies such as those mentioned above.
  • the aim of the present invention is to provide compositions that effectively reduce A ⁇ O neurotoxicity and compositions that are useful for the prevention and treatment of AD.
  • a composition for prevention and/or treatment for AD comprises tyrosol, a derivative thereof, and/or a salt thereof, as an effective component.
  • composition for reducing A ⁇ O neurotoxicity comprises tyrosol, a derivative thereof, and/or a salt thereof, as an effective component.
  • the present invention provides the composition that reduces A ⁇ O neurotoxicity as well as the composition for prevention and/or treatment for AD.
  • FIG.1 shows the results of Western blot analysis of the effect of the plant (Rodiola rosea) extract.
  • Fig 2 shows the results of Western blot analysis to examine the effects of the plant constituents contained in Rodiola rosea.
  • Fig 3 shows the results of Western blot analysis to examine the effects of different concentrations of tyrosol.
  • Fig 4 shows the results of ThT assay to examine the effect of tyrosol onthe aggregation of A ⁇ 42.
  • FIG 5 Fig 5 shows the experimental paradigm describing tyrosol administration to AD model mice and the subsequent experiments.
  • Fig 6 shows changes in body weight of mice during tyrosol treatment.
  • FIG 7 shows the results of Barnes maze test.
  • FIG 8 shows the results of A ⁇ immunostaining confirming A ⁇ deposition in the hippocampus and cerebral cortex of transgenic mice treated with water and those treated with tyrosol for 20 weeks.
  • Fig 9 shows the results of quantitative analysis of A ⁇ burden in Fig 8.
  • Fig 10 shows the results of quantitative analysis of the amounts of A ⁇ 40 and A ⁇ 2 accumulated in the cerebral cortical tissues in the two groups of mice.
  • FIG 11 Fig 11 shows the region of interest in the mouse hippocampus.
  • Fig 12 shows the results of spinophilin immunostaining of the hippocampal regions of the mice treated for 20 weeks.
  • FIG 13 shows the results of the quantitative analysis of spinophilin immunofluorescence intensity in the hippocampal regions of the mice treated for 12 or 20 weeks.
  • FIG 14 shows the results of 4-HNE immunostaining in the CA3 region of the hippocampus of the mice treated for 20 weeks.
  • Fig 15 shows the results of the quantitative analysis of 4-HNE immunofluorescence intensity in the CA3 region of the mice treated for 12 or 20 weeks.
  • Fig 16 shows the results of HEL (hexanoyl-lysine adduct) immunostaining of neurons treated with A ⁇ O or A ⁇ O plus tyrosol.
  • composition for the prevention and/or treatment for AD in this embodiment includes at least one of tyrosol, a derivative thereof, and a salt thereof, as effective components.
  • composition for the prevention and treatment has an effect to reduce A ⁇ O neurotoxicity, it is also the composition that reduces A ⁇ O neurotoxicity.
  • “tyrosol” is a chemical compound described in the following structural formula.
  • the chemical compound is an effective component in the exertion of the effect of the composition. As confirmed by the experiments described below, the component has an effect to reduce the neurotoxicity of A ⁇ O, possibly resulting in suppression of the neurodegeneration in the brain.
  • the chemical compound is capable of exhibiting beneficial effects in both the prevention and the treatment of AD.
  • “derivative” implies any chemical compound in which the structure of tyrosol is partially modified within the range which is pharmacologically acceptable; for example, it includes such as an ester in which tyrosol is bonded with an acid or a chemical in which hydrogen is substituted with another substituent; however “derivative” is not limited to them.
  • the acid to form an ester includes, but not limited to, formic acid, acetic acid, propionic acid, and butyric acid.
  • salt implies any salt formed by the reaction of tyrosol or its derivative with a base, which is pharmacologically acceptable and shows the same or similar effect as the tyrosol or the derivative thereof.
  • the examples of the salt include such as sodium salt, potassium salt, calcium salt, and magnesium salt.
  • composition can be used for at least one of the treatment and the prevention, as mentioned above, and its product can be pharmaceutical (drug) or food (functional food).
  • composition is a pharmaceutical, it can achieve the prevention or the treatment by administering to patients suffering from AD or MCI due to AD or individuals with a high risk of morbidity.
  • the form of administration is not limited as far as it is effective and includes oral drugs such as tablets, capsules, granules, and syrup, external drugs such as patches and ointment, and injectable drug such as fluid medicine.
  • oral drugs such as tablets, capsules, granules, and syrup
  • external drugs such as patches and ointment
  • injectable drug such as fluid medicine.
  • the composition can be administered orally, through injection, sublingually and through the skin.
  • the drug can contain other substances than the effective ingredients, i.e., various additives such as excipients, stabilizers, preservatives, buffering agents, suspending agents, emulsifiers, colorants, incense agents, and viscosity modifiers. It is also possible that the drug can contain solvents such as water and saline as far as they do not alter the quality and effect of the composition.
  • composition is a food, as in the case of a pharmaceutical, it can be used for the prevention and the treatment (improvement) of AD.
  • “food” represents beverages including tea, coffee, lactic acid bacteria beverages, and milk, fresh foods including meat, seafood, egg, grains, beans, potatoes, vegetables, seaweeds, and fruits, fermented foods including yogurt and natto, processed foods made of natural foods, fats and edible oils including salad oil, olive oil, soybean oil, and corn oil, and seasonings including soy source and miso; ‘food’ is not limited to these as far as it is taken by individuals.
  • This ‘food’ also includes supplements in which the effective ingredients are mixed with powders or concentrates of any food described above or any additive described above including excipients. In case the effective ingredients are extracted from raw materials, such extracts themselves can be a food composition.
  • the amount of the effective ingredient of this composition can be different depending on whether its form is a pharmaceutical or a food, and can be adjusted appropriately depending on symptoms and body weights of subjects to be administered.
  • the amount can preferably be more than 0.5 mg/kg/day, and more preferably be more than 1 mg/kg/day; these dosages would achieve the effect of this composition.
  • Tyrosol, its derivative and their salt (designated as tyrosol et al.) in the present composition can be manufactured by chemical synthesis but obtained by extracting from plants which contain tyrosol et al.
  • the kinds of plants are not limited, but those containing high amounts of tyrosol et al. per volume or weight are preferable, including Rhodiola rosea L., Sinopodophyllum emodi (WALL.) YING, Rhodiola crenulate (HOOK. F. et Thoms.) H. OHBA, Rhodiola sachalinensis, Olea europaea, Engelhardia roxburghiana, and Fraxinus americana.
  • the methods of extraction are not limited and known methods can be applied.
  • water or organic solvent such as alcohol, acetone, and hexane or a mixture of at least two of these can be used as an extraction solvent.
  • alcohol is not limited but includes methanol, ethanol, propanol, isopropanol, butanol, and isobutanol.
  • ethanol is more preferable.
  • the ethanol content can preferably be 5 to 95 weight %, and more preferably be 10 to 90 weight %.
  • the present compositions reasonably act as those having an effect to reduce A ⁇ O neurotoxicity and those for the prevention and treatment of AD.
  • the present compositions contain tyrosol et al. as effective components, and can easily be administered orally.
  • the compositions exert their effect through a mechanism different from those of the known therapeutic and prophylactic compounds that are being developed for AD, and can be used in combination with such ones, possibly resulting in synergistic effects.
  • the present compositions have simple chemical structures and can be manufactured relatively easily; they are contained in natural plants, as described above, and have a high safety profile.
  • tyrosol is a relatively small molecule and can be transported into the brain where it exerts its activity after administration to the body.
  • Rhizomes of Rhodiola rosea were extracted into water at 80°C and centrifuged to obtain the R. R. extract.
  • rat primary neurons (9 days in vitro) were treated without or with 2.5 ⁇ M A ⁇ O or 2.5 ⁇ M A ⁇ O plus the plant extracts described above for 3 days, followed by western blot analysis with anti-active caspase-3.
  • a ⁇ O was prepared from synthetic A ⁇ 42 by the previously reported method, and used after dilution with culture medium. The results are shown in Fig. 1, in which C, O, O+E1 represent untreated, treated with A ⁇ O, and treated with A ⁇ O plus E1 (R. R. extracts; 10 ⁇ g/ml), respectively.
  • the active caspase-3 level was used as a marker of apoptosis.
  • FIG. 3 shows the results of the experiment in which 5 ⁇ M or 10 ⁇ M of tyrosol was used.
  • neurons were treated with A ⁇ O (O) or A ⁇ O plus 5 ⁇ M (T5) or 10 ⁇ M (T10) of tyrosol.
  • a ⁇ , A ⁇ +EGCG (epigallocatechin gallate), A ⁇ +T10, A ⁇ +T25, A ⁇ +T50, and A ⁇ +T100 indicate A ⁇ (50 ⁇ M) only, A ⁇ with 50 ⁇ M EGCG, A ⁇ with 10 ⁇ M tyrosol, A ⁇ with 25 ⁇ M tyrosol, A ⁇ with 50 ⁇ M tyrosol, and A ⁇ with 100 ⁇ M tyrosol, repectively.
  • AD model mice Next, AD (Alzheimer’s disease) model mice (5XFAD Transgenic (Tg) mice) and wild-type mice (Non) were used to examine the therapeutic effects of tyrosol. 5XFAD mice which overexpress mutant amyloid- ⁇ precursor protein and mutant presenilin 1 were obtained from MMRRC in the United States, and maintained by crossing with C57BL/6 mice.
  • Tg mice and Non mice were administered only water as control; these mice were designated Tg-Veh mice and Non-Veh mice. And Tg mice and Non mice were administered tyrosol-containing water (the amount of tyrosol was about 12.5 mg/kg/day); these mice were designated Tg-Tyr mice and Non-Tyr mice.
  • Two series of experiments were performed; in one, tyrosol was administered for 12 weeks (from 4 to 7 months of age), and in the other, it was administered for 20 weeks (from 2 to 7 months of age). In 5XFAD mice, A ⁇ plaques consisting of aggregated A ⁇ appeared around 3 months of age.
  • Fig. 5 depicts the treatment paradigm, in which tyrosol was administered by supplying water containing tyrosol (25 ⁇ M) ad libitum in the feed-water bottle.
  • Fig. 6 depicts changes of body weights of mice during the treatment periods. The data indicate that body weights were almost the same among the mice treated with vehicle (water) and tyrosol. In addition, after the treatment, levels of albumin, urea nitrogen, and ALT (alanine aminotransferase) in the serum were also equivalent among these treated and untreated Tg mice and Non mice. These results confirm that tyrosol itself has no toxicity and safe within the tested dose.
  • mice in the Tg-Tyr group tended to spend more time around the holes in the target quadrant than in the non-target quadrants, but those in the Tg-Veh group did not. (data not shown)
  • FIG 8 shows the images of A ⁇ immunohistochemical analysis in the hippocampus (upper) and cerebral cortex (lower) of mice treated with vehicle (Tg-Veh) or tyrosol (Tg-Tyr) for 20 weeks.
  • Fig 9 shows the results of quantification of A ⁇ burden in these areas.
  • ELISA analysis of A ⁇ 40 and A ⁇ 42 accumulated in the cortex disclosed that the amounts of A ⁇ 40 and A ⁇ 42 were comparable between vehicle-treated and tyrosol-treated mice, confirming that tyrosol does not affect A ⁇ accumulation.
  • Western blot analysis of cortical extracts indicated that the level of amyloid- ⁇ precursor protein (A ⁇ PP) were similar between the two groups (data not shown).
  • Figs 11-13 show ROIs (region of interest) in the mouse hippocampus
  • Fig 12 shows the representative images of immunostaining of hippocampal regions after treatment for 20 weeks.
  • Fig 13 shows quantitative data of spinophilin intensities in these areas after treatment for 12 or 20 weeks.
  • tyrosol is capable of preventing A ⁇ O-induced oxidative stress
  • immunocytochemical analysis of cultured neurons was performed using an antibody to HEL (hexanoyl-lysine adduct), a marker of oxidative damage by lipid peroxidation.
  • HEL hexanoyl-lysine adduct
  • the data showed that HEL immunoreactivity was detected in the cell soma and proximal neurites and was more intense in A ⁇ O-treated neurons than control neurons, reflecting induction of oxidative stress by A ⁇ O.
  • HEL immunoreactivity in neurons co-treated with A ⁇ O and 5 ⁇ M tyrosol was similar to that in control, suggesting an anti-oxidative effect of tyrosol.
  • tyrosol one of the main constituents of the plant R. R., can be an agent that protects neurons from the neurotoxicity of A ⁇ O.
  • the present invention has a potential for industrial applicability as compositions for the prevention and/or treatment for AD and those that effectively reduce A ⁇ O neurotoxicity.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention a pour but de fournir des compositions qui réduisent efficacement la neurotoxicité AβO et des compositions qui s'utilisent dans le cadre de la prévention et du traitement de la maladie d'Alzheimer. Pour atteindre ce but, selon un aspect de la présente invention, une composition servant à prévenir et/ou à traiter la maladie d'Alzheimer et/ou la démence d'Alzheimer comprend du tyrosol, un dérivé de ce dernier et/ou un sel de ce dernier en tant que composant efficace. En outre, selon un autre aspect de la présente invention, une composition permet de réduire la neurotoxicité de l'oligomère bêta-amyloïde et comprend du tyrosol, un dérivé de ce dernier et/ou un sel de ce dernier en tant que composant efficace. En outre, selon un autre aspect de la présente invention, une composition servant à prévenir et/ou à traiter la maladie d'Alzheimer et/ou la démence d'Alzheimer comprend un extrait de plante en tant que composant efficace, qui comprend du tyrosol, un dérivé de ce dernier et/ou un sel de ce dernier. En outre, selon un autre aspect de la présente invention, une composition servant à réduire la neurotoxicité de l'oligomère bêta-amyloïde comprend un extrait de plante en tant que composant efficace, qui comprend du tyrosol, un dérivé de ce dernier et/ou un sel de ce dernier.
PCT/JP2020/016483 2019-04-15 2020-04-14 Composition servant à prévenir et/ou à traiter la maladie d'alzheimer et/ou la démence d'alzheimer, et composition servant à réduire la neurotoxicité de l'oligomère bêta-amyloïde WO2020213616A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2019-077107 2019-04-15
JP2019077107 2019-04-15
JP2020-068069 2020-04-06
JP2020068069A JP7333626B2 (ja) 2019-04-15 2020-04-06 アルツハイマー型認知症予防・治療用組成物、アミロイドβオリゴマー神経毒性低減用組成物

Publications (1)

Publication Number Publication Date
WO2020213616A1 true WO2020213616A1 (fr) 2020-10-22

Family

ID=72837891

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2020/016483 WO2020213616A1 (fr) 2019-04-15 2020-04-14 Composition servant à prévenir et/ou à traiter la maladie d'alzheimer et/ou la démence d'alzheimer, et composition servant à réduire la neurotoxicité de l'oligomère bêta-amyloïde

Country Status (1)

Country Link
WO (1) WO2020213616A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003082259A1 (fr) * 2002-04-03 2003-10-09 Puleva Biotech, S.A. Produits phenoliques naturels et leurs derives permettant d'obtenir une protection contre les maladies neurodegeneratives

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003082259A1 (fr) * 2002-04-03 2003-10-09 Puleva Biotech, S.A. Produits phenoliques naturels et leurs derives permettant d'obtenir une protection contre les maladies neurodegeneratives

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JAYASENA, T. ET AL.: "The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer's disease", AGEING RESEARCH REVIEWS, vol. 12, 2013, pages 867 - 883, XP028783216, DOI: 10.1016/j.arr.2013.06.003 *

Similar Documents

Publication Publication Date Title
Han et al. Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy
Esposito et al. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes
Choi et al. Natural products from marine organisms with neuroprotective activity in the experimental models of Alzheimer’s disease, Parkinson’s disease and ischemic brain stroke: Their molecular targets and action mechanisms
Omar Biophenols pharmacology against the amyloidogenic activity in Alzheimer’s disease
KR20110013466A (ko) 신경퇴행성 질환을 치료 및 예방하기 위한 방법
EP3622952A1 (fr) Agent servant à favoriser la décomposition et l'excrétion d'amyloïdes-
US20220387542A1 (en) Protective effects of oil palm composition on alzheimer's disease
KR101807953B1 (ko) 고수 추출물을 유효성분으로 하는 치매 예방 또는 치료용 약학적 조성물
WO2020213616A1 (fr) Composition servant à prévenir et/ou à traiter la maladie d'alzheimer et/ou la démence d'alzheimer, et composition servant à réduire la neurotoxicité de l'oligomère bêta-amyloïde
JP7333626B2 (ja) アルツハイマー型認知症予防・治療用組成物、アミロイドβオリゴマー神経毒性低減用組成物
JP2024505458A (ja) コリンエステラーゼ阻害剤および抗酸化剤を含む脳疾患を治療するための医薬組成物
KR102120376B1 (ko) 승마 추출물, 이의 분획물 또는 승마에서 유래된 화합물을 유효성분으로 포함하는 퇴행성 뇌질환의 예방 또는 치료용 조성물
JP7106340B2 (ja) 血液脳関門保護剤
JP6398014B2 (ja) ラマリンを含有する退行性脳疾患の予防または治療用組成物
KR102583195B1 (ko) 퀴노바산을 포함하는 퇴행성 뇌질환 예방 또는 치료용 조성물
EP2845589B1 (fr) Composition pour la prévention et le traitement de la migraine ou de la douleur neuropathique
US20130261147A1 (en) Composition for preventing or treating dementia
JP3943399B2 (ja) ヤマブシダケ由来脂溶性抽出成分
KR102612229B1 (ko) N-[(4'-브로모[1,1'-바이페닐]-4-일)설포닐]-l-발린 또는 이의 약제학적으로 허용 가능한 염을 포함하는 아밀로이드 베타의 올리고머화 및 피브릴화 억제용 조성물
KR102478582B1 (ko) 에버닉산을 유효성분으로 함유하는 파킨슨 질환 예방 또는 치료용 조성물
KR102432016B1 (ko) 신경염증질환 예방 또는 치료용 조성물
KR102294523B1 (ko) 진세노사이드 Rb2를 포함하는 신경세포 보호용 조성물
KR102632728B1 (ko) 고장초 추출물을 유효성분으로 함유하는 퇴행성 뇌질환 예방 또는 치료용 조성물
KR102282883B1 (ko) 승마 추출물, 이의 분획물 또는 승마에서 유래된 화합물을 유효성분으로 포함하는 퇴행성 뇌질환의 예방 또는 치료용 조성물
KR102102868B1 (ko) 고시페틴(Gossypetin)을 포함하는 퇴행성 뇌질환 예방 또는 치료용 조성물

Legal Events

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

Ref document number: 20791118

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20791118

Country of ref document: EP

Kind code of ref document: A1