WO2018074793A1 - Composition améliorant la fonction cognitive comprenant un nouveau composé à base de kaempférol dérivé du thé post-fermenté - Google Patents

Composition améliorant la fonction cognitive comprenant un nouveau composé à base de kaempférol dérivé du thé post-fermenté Download PDF

Info

Publication number
WO2018074793A1
WO2018074793A1 PCT/KR2017/011401 KR2017011401W WO2018074793A1 WO 2018074793 A1 WO2018074793 A1 WO 2018074793A1 KR 2017011401 W KR2017011401 W KR 2017011401W WO 2018074793 A1 WO2018074793 A1 WO 2018074793A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
beta
compound
formula
less
Prior art date
Application number
PCT/KR2017/011401
Other languages
English (en)
Korean (ko)
Inventor
홍용덕
최민식
조시영
김정기
Original Assignee
(주)아모레퍼시픽
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 KR1020170119273A external-priority patent/KR102394643B1/ko
Application filed by (주)아모레퍼시픽 filed Critical (주)아모레퍼시픽
Priority to CN201780064682.4A priority Critical patent/CN109843087B/zh
Priority to JP2019518490A priority patent/JP6974450B2/ja
Priority to US16/340,753 priority patent/US20210322452A1/en
Publication of WO2018074793A1 publication Critical patent/WO2018074793A1/fr

Links

Images

Classifications

    • 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
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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)
    • A61K36/82—Theaceae (Tea family), e.g. camellia

Definitions

  • the present specification relates to a composition for improving cognitive function comprising a novel camphorol-based compound.
  • Neuronal dysfunction and damage can be caused by certain proteins that are prone to aggregation, and many neurological diseases are characterized by such conditions.
  • Such nervous system diseases include diseases such as Alzheimer's disease.
  • Green tea is brewed in the form of leaf tea, or fermented tea for a deeper flavor.
  • Fermented green tea means that the green tea leaves are subjected to oxidation treatment, including fermented tea oxidized by the oxidase present in the tea leaves, and post-fermented tea fermented by a separate microorganism other than the enzyme present in the tea leaves. .
  • oxidation treatment including fermented tea oxidized by the oxidase present in the tea leaves, and post-fermented tea fermented by a separate microorganism other than the enzyme present in the tea leaves.
  • it can be classified into weakly fermented tea, semi-fermented tea, and fully fermented tea.
  • fermented green tea is called by various names, such as green tea, oolong tea, black tea, black tea, etc., depending on the type and extent of fermentation.
  • the fermented tea may not only exhibit a difference in flavor compared to the green tea, but may also show a large difference in the type and content of the active ingredient depending on the specific fermentation process and the type of microorganism. Since various compounds can be produced and separated as described above, various efforts for separating and identifying unknown new compounds using green tea have been continued.
  • an object of the present invention is to discover a novel compound derived from post-fermented tea and use it for improving cognitive function and protecting neurons.
  • It provides a compound of Formula 1, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, or a post-fermented tea extract comprising the same as an active ingredient, a composition for improving cognitive decline.
  • R 1 may be C 15 H 9 O 6
  • R 2 may be C 6 H 11 O 5
  • R 3 may be C 9 H 7 O 2 .
  • nerve cells for protection or neurological diseases comprising the compound, isomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, solvates thereof, or post-fermented tea extracts comprising the same as an active ingredient.
  • a therapeutic composition is provided.
  • the present invention relates to administering to a subject in need thereof an effective amount of the compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, or an after-fermented tea extract comprising the same.
  • an effective amount of the compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, or an after-fermented tea extract comprising the same.
  • a method for improving cognitive decline a method for treating cognitive decline, a method for protecting neurons, or a method for treating neurological diseases.
  • the present invention provides a use for the production of a composition for protecting neurons, or treating neurological diseases.
  • the present invention provides a solvate, or a post-fermented tea extract comprising the same.
  • the present invention in another aspect, to improve the cognitive function, nerve cell protection as an active ingredient for the compound, isomers thereof, pharmaceutically acceptable salts thereof, hydrates, solvates thereof, or post-fermentation comprising the same Provides non-therapeutic use of tea extracts.
  • the present invention can be widely used in post-fermented tea-related industries, cognitive functions, and neuroscience by allowing the new compounds isolated from post-fermented tea to be used in the field of cognitive improvement and neuronal protection. have.
  • Figure 2 shows the 1 H-NMR (nuclear magnetic resonance) spectrum of the compound according to an aspect of the present invention.
  • Figure 3 shows the 13 C-NMR spectrum of the compound according to an aspect of the present invention.
  • FIG 4 shows the 1 H- 13 C Heteronuclear Single Quantum Coherence (HSQC) spectrum of the compound according to an aspect of the present invention.
  • HSQC Single Quantum Coherence
  • FIG. 5 shows the 1 H- 13 C Heteronuclear Multiple-Bond Coherence (HMBC) spectrum of the compound according to an aspect of the present invention.
  • HMBC Heteronuclear Multiple-Bond Coherence
  • Figure 6 confirms the effect of the compound on the aggregation of beta amyloid according to an aspect of the present invention.
  • Post-fermentation includes fermentation by a separate microorganism or substance other than the enzyme present in tea leaves.
  • Post-fermented tea includes fermented green tea by the above method.
  • extract includes any material obtained by extracting a component therefrom from a natural product, regardless of the method of extraction or the kind of the component. For example, extracting a component that is dissolved in a solvent from a natural product using water or an organic solvent, extracting only a specific component such as oil, such as oil, and fraction obtained by using a specific solvent again It is a broad concept that includes all of one fraction.
  • fraction includes fractionating or extracting a specific substance or extract using a certain solvent, and extracting them again with a specific solvent. Fractionation methods and extraction methods can be any method known to those skilled in the art.
  • isomers in particular are not only optical isomers (eg, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof), but also form isomers ( conformation isomers (ie, isomers that differ only by their angles of one or more chemical bonds), position isomers (especially tautomers) or geometric isomers (eg, cis-trans isomers) do.
  • essentially pure means at least about 90%, preferably at least about 95%, of a specific compound, for example enantiomers or diastereomers, when used in connection with an enantiomer or diastereomer. More preferably at least about 97% or at least about 98%, even more preferably at least about 99%, even more preferably at least about 99.5% (w / w).
  • pharmaceutically acceptable refers to the approval of a government or equivalent regulatory body for use in animals, more specifically in humans, by avoiding significant toxic effects when used in conventional medicinal dosages. It is meant to be recognized or approved, or recognized as listed in a pharmacopoeia or other general pharmacopoeia.
  • salts means salts according to one aspect of the invention that are pharmaceutically acceptable and have the desired pharmacological activity of the parent compound.
  • the salt is formed from (1) an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or the like; Or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenes
  • hydrate refers to a compound to which water is bound, and is a broad concept including an inclusion compound having no chemical bonding force between water and the compound.
  • solvate means a higher order compound produced between molecules or ions of a solute and molecules or ions of a solvent.
  • the present invention in one aspect, for improving the cognitive function of a compound of formula 1, its isomers, pharmaceutically acceptable salts thereof, hydrates thereof, solvates thereof, or post-fermented tea extracts comprising the same as an active ingredient To provide a composition.
  • R 1 may be C 15 H 9 O 6
  • R 2 may be C 6 H 11 O 5
  • R 3 may be C 9 H 7 O 2 .
  • R 1 may be a compound of Formula 2 below.
  • R 2 may be a compound of Formula 3 below.
  • R 3 may be a compound of Formula 4 below.
  • the compound is camphorol3-O- [2-O ''-(E) -p-coumaroyl] [beta-D-glucopyranosyl- (1 ⁇ 3) -O-alpha -L-Ranmopyranosyl- (1 ⁇ 6) -O-beta-D-glucopyranoside] (Kaempferol3-O- [2-O ''-(E) -p-coumaroyl] [beta-D-glucopyranosyl -(1 ⁇ 3) -O-alpha-L-rhamnopyranosyl- (1 ⁇ 6) -O-beta-D-glucopyranoside]).
  • the compound may be represented by the following Formula 5.
  • the compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a method of preparing a hydrate thereof or a solvate thereof may include synthesis, separation from natural products, and the like.
  • the post-fermentation may be by strain inoculation, the strain may be Saccharomyces sp., Bacillus sp. Lactobacillus sp. And lucono Saccharomyces cerevisiae , Lactobacillus casei , Bacillus subtlis , Lactobacillus Bulgarian ( Lactobacillus bulgarius ) and Leuconostoc mesenteroides ).
  • the post-fermented tea may be after fermenting green tea.
  • the compound is a compound discovered by the present inventors after the continuous study of the post-fermented tea, the beta-amyloid aggregation assay (beta-Amyloid aggregation assay) using the compound, as known It was confirmed that the inhibitory effect of beta amyloid aggregation and plaque formation was better than the inhibitors such as morphine and phenol red. Therefore, it has been found that the compound according to one aspect of the present invention can be used to prevent, treat, and ameliorate cognitive decline related to beta-amyloid, and also prevent neurons from damage and death due to beta-amyloid aggregation. It was demonstrated that the compound can be used for the purpose of protecting (see FIG. 6).
  • the compound enhanced BDNF expression in neurons and decreased the expression of DNMT1. That is, the present invention was found to be useful for the prevention and treatment of neurodegenerative diseases such as cognitive decline, dementia, and Alzheimer's disease associated with decreased BDNF expression or enhanced DNMT1 expression.
  • the present invention relates to administering to a subject in need thereof an effective amount of the compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, or an after-fermented tea extract comprising the same. It may be a method for improving cognitive decline, a method for treating cognitive decline, a method for protecting neurons, or a method for treating neurological diseases.
  • the present invention the compound, isomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, solvates thereof, or post-fermented tea extracts comprising the same for improving cognitive function, treatment for cognitive decline It may be related to the use for the production of a composition for the protection of neurons, or the treatment of neurological diseases.
  • the present invention in another aspect, to improve the cognitive function, nerve cell protection as an active ingredient for the compound, isomers thereof, pharmaceutically acceptable salts thereof, hydrates, solvates thereof, or post-fermentation comprising the same It may be related to the non-therapeutic use of tea extract.
  • the extraction may be extraction with one or more solvents selected from water, hydrothermal water, C 1 to C 6 lower alcohols, and mixed solvents thereof, and in other embodiments, the lower alcohols are It may be an alcohol alone or a mixture which can be generally used in, preferably ethanol.
  • the extract may be a fraction fractionated into ketones after extraction.
  • the ketone is acetone, carbon, pulegone, isolongifolanone, 2-heptanone, 2-pentanone, 3-hexanone, 3-heptanone , 4-heptanone, 2-octanone, 3-octanone, 2-nonanone, 3-nonanone, 2-undecanone, 2-tridecanone, methyl isopropyl ketone, ethyl isoamyl ketone, butyl Dencetone, methylheptenone, dimethyloctenone, geranyl acetone, farnesyl acetone, 2,3-pentadione, 2,3-hexadione, 3,4-hexadione, 2,3-heptadione, amylcyclopenta Paddy, amylcyclopentenone, 2-cyclopentyl cyclopentanone, hexylcyclopentanone, 2-n-heptylcyclopentanone,
  • the content of the compound of formula 1, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof in the composition may be 0.00001% to 10% by weight relative to the total weight of the composition.
  • the content is 0.00001% by weight, 0.00005% by weight, 0.0001% by weight, 0.0005% by weight, 0.001% by weight, 0.005% by weight, 0.01% by weight, 0.05% by weight, 0.1% by weight based on the total weight of the composition At least 0.5%, at least 0.5%, at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, or 9 It may be at least weight percent.
  • the content of the post-fermented tea extract in the composition may be 0.1% to 90% by weight relative to the total weight of the composition.
  • the content is 0.1% by weight, 1% by weight, 5% by weight, 10% by weight, 15% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight relative to the total weight of the composition.
  • the extract is a compound of Formula 1, isomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof is at least 0.0001% by weight, 0.0005% by weight based on the total weight of the extract Or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.05 or more, 0.1 or more, 0.5 or more, 1 or more, 3 or more, 5 or more, 7 or more % Or more, 10% or more, 12% or more, 15% or more, or 18% or more by weight may be included.
  • 20 wt% or less 15 wt% or less, 12 wt% or less, 10 wt% or less, 7 wt% or less, 5 wt% or less, 3 wt% or less, 1 wt% or less, 0.5 wt% or less, 0.1 wt% Or less, 0.05 wt% or less, 0.01 wt% or less, 0.005 wt% or less, 0.001 wt% or less, 0.0005 wt% or less, or 0.0003 wt% or less.
  • the extract may include 0.0001 wt% to 20 wt% of the compound of Formula 1, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof based on the total weight of the extract. .
  • the dosage of the compound of Formula 1, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof by administration of the composition is from 0.001 mg / kg / day to May be 100 mg / kg / day.
  • the dosage is at least 0.001 mg / kg / day, at least 0.005 mg / kg / day, at least 0.01 mg / kg / day, at least 0.05 mg / kg / day, at least 0.1 mg / kg / day, 0.5 mg / kg / day Or more, 1 mg / kg / day or more, 5 mg / kg / day or more, 10 mg / kg / day or more, 15 mg / kg / day or more, 20 mg / kg / day or more, 25 mg / kg / day or more, 30 mg / kg / day or more , At least 35 mg / kg / day, at least 40 mg / kg / day, at least 45 mg / kg / day, at least 50 mg / kg / day, at least 55 mg / kg / day, at least 60 mg / kg / day, at least 65 mg / kg / day, At least 7 mg / kg / day, at least 75 mg / kg / day,
  • the dosage is 100 mg / kg / day or less, 95 mg / kg / day or less, 90 mg / kg / day or less, 85 mg / kg / day or less, 80 mg / kg / day or less, 75 mg / kg / day or less, 70 mg / kg / day or less, 65 mg / kg / day or less, 60 mg / kg / day or less, 55 mg / kg / day or less, 50 mg / kg / day or less, 45 mg / kg / day or less, 40 mg / kg / day or less, 35 mg / kg / Day or less, 30mg / kg / day or less, 25mg / kg / day or less, 20mg / kg / day or less, 15mg / kg / day or less, 10mg / kg / day or less, 5mg / kg / day or less, 1mg / kg / Days or less, 0.5 mg / kg / day or less
  • the cognitive decline is beta amyloid ( ⁇ -amyloid) aggregation, beta amyloid plaque formation, or brain-derived neurotrophic factor (BDNF) expression and DNMT1 (DNA (cytosine-5) -methyltransferase 1) may be due to any one or more selected from the group consisting of increased expression.
  • beta amyloid ⁇ -amyloid
  • BDNF brain-derived neurotrophic factor
  • DNMT1 DNA (cytosine-5) -methyltransferase 1) may be due to any one or more selected from the group consisting of increased expression.
  • the cognitive decline may include one or more selected from the group consisting of memory loss, cognitive decline, discrimination decline, depression, and forgetfulness.
  • the improvement consists of inhibiting beta-amyloid aggregation, inhibiting beta-amyloid plaque formation, degrading beta-amyloid plaques or aggregated beta-amyloid, enhancing BDNF expression and decreasing DNMT1 expression. It may be through one or more selected from the group.
  • the composition may be a composition for protecting nerve cells.
  • the neuronal cell protection may be to protect the neuron from the effects of aggregation or plaque of beta amyloid, reduced BDNF expression, or enhanced DNMT1 expression. Since aggregated beta amyloid is known to damage and kill nerve cells, according to one aspect of the present invention, it is possible to protect nerve cells when inhibiting aggregation or plaque formation of beta amyloid.
  • DNMT1 inhibits gene expression by causing DNA methylation, which causes problems in BDNF expression and the like, leading to a decrease in cognitive ability.
  • the present invention inhibits DNA methyltransferase 1 (DNMT1) activity and inhibits DNA methylation, thereby helping to improve cognitive ability and neurodegenerative disease through neuronal protection.
  • DNMT1 DNA methyltransferase 1
  • the composition may be a pharmaceutical composition or a food composition.
  • the composition may be a pharmaceutical composition for preventing or treating neurodegenerative diseases.
  • the neurodegenerative disease may be due to one or more selected from the group consisting of beta amyloid ( ⁇ -amyloid) aggregation, decreased BDNF expression, and increased DNMT1 expression.
  • the neurodegenerative disease includes dementia, Alzheimer's disease, forgetfulness and the like.
  • compositions according to an aspect of the present invention may be administered orally, parenteral, rectal, topical, transdermal, intravenous, intramuscular, intraperitoneal, subcutaneous.
  • Formulations for oral administration may be tablets, pills, soft and hard capsules, granules, powders, granules, solutions, emulsions or pellets, but are not limited thereto. It is not.
  • Formulations for parenteral administration may be, but are not limited to, solutions, suspensions, emulsions, gels, injections, drops, suppositories, patches or sprays.
  • the formulations can be readily prepared according to conventional methods in the art and include surfactants, excipients, hydrating agents, emulsifiers, suspending agents, salts or buffers for controlling osmotic pressure, colorants, spices, stabilizers, preservatives, preservatives or Other commercially available auxiliaries may further be included.
  • the dosage or dosage of the pharmaceutical composition according to one aspect of the present invention will vary depending on the age, sex, weight, pathology and severity of the subject to be administered, the route of administration or the judgment of the prescriber. Application amount determination based on these factors is within the level of skill in the art.
  • the formulation of the food composition is not particularly limited, but may be, for example, formulated into tablets, granules, pills, powders, liquids such as drinks, caramels, gels, bars, tea bags, and the like.
  • the food composition of each formulation may be suitably selected by a person skilled in the art according to the formulation or purpose of use in addition to the active ingredient, and may be synergistic when applied simultaneously with other raw materials.
  • composition may be administered by various methods such as simple ingestion, drinking, injection administration, spray administration or squeeze administration.
  • the dosage determination of the active ingredient is within the level of those skilled in the art and may vary depending on various factors such as age, health condition, complications, etc. of the subject to be administered.
  • the food composition according to an aspect of the present invention may be processed foods of any type, such as, for example, various foods such as chewing gum, caramel products, candy, ice cream, confectionery, and beverage products such as soft drinks, mineral water, and alcoholic beverages. It may be a health functional food, including vitamins and minerals.
  • the food composition according to an aspect of the present invention is a flavor, such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and enhancers (such as cheese, chocolate), pectic acid and its Salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • the food compositions according to an aspect of the present invention may include a pulp for producing natural fruit juice and fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not so critical but is typically included in the range of 0 to about 50 parts by weight per 100 parts by weight of the composition according to one aspect of the invention.
  • the water content was adjusted to 40 wt% by adding water to the green tea made from green tea ( Camellia sinensis var. Yabukita ) leaves.
  • Bacillus subtillis Bacillus subtillis 5 ⁇ 10 6 cfu / g was inoculated, fermented for 3 days at 50 °C and then fermented at 80 °C 4 days.
  • the aged tea sample was ground for 15 seconds and filtered through a stainless steel sieve of mesh size 1 mm. Thereafter, the pulverized 50mg was added to 1.5ml Eppendorf tube, 1ml of deionized water was added, stirred at a constant speed for 30 minutes in a 60 ° C constant temperature water bath, and centrifuged for 15 minutes at 25 ° C 13,000rpm. Only insoluble portions of the dried fermented green tea extract were separated.
  • 150 g of the post-fermented tea sample was fractionated with acetone to remove catechin derivatives and caffeine and to obtain a soluble substance in which other compounds were concentrated.
  • acetone solubles a fraction of 5: 1 (v / v) of chloroform: methanol was first obtained by using silica gel column chromatography as a solvent.
  • each of the compounds is a novel compound which is not known previously, and is a camphorol 3-O- [2-O ''-(E) -p-coumaroyl] having a molecular weight of 902.2481 of C 42 H 46 O 22 .
  • Camperol 3-O- [2-O ''-(E) -p-coumaroyl] [beta-D-glucopyranosyl- (1 ⁇ 3) -O-alpha-L-ramnopyranosyl- (1 ⁇ 6) -O-beta-D-glucopyranoside] is shown below.
  • Camperol 3-O- [2-O ''-(E) -p-coumaroyl] [beta-D-glucopyranosyl- (1 ⁇ 3) -O-alpha-L-ramnopyranosyl- (1 6) -O-beta-D-glucopyranoside] is shown in Figure 1
  • 1 H-NMR spectrum and 13 C-NMR spectrum is shown in Figure 2 and 3, respectively
  • HSQC Heteronuclear Single Quantum Coherence
  • HMBC Heteronuclear Multiple-Bond Coherence
  • beta-amyloid (A ⁇ 1-42, AnaSpec Inc, USA) was obtained and used at a concentration of 0.1 mg / ml, and stored at -80 ° C before use.
  • RFU is relative fluorescence unit and “Increased RFU” is the amount of aggregated beta amyloid, and “Increased RFU (% of Pos. Cont.)” Is the percentage value of the amount of aggregated beta amyloid compared to the positive control.
  • New Material 33 refers to camphorol 3-O- [2-O ''-(E) -p-coumaroyl] [beta-D-glucopyranosyl- (1 ⁇ 3) -O-alpha-L- Rhamnopyranosyl- (1 ⁇ 6) -O-beta-D-glucopyranoside].
  • the two compounds have the same efficacy, and thus can be used for the prevention, treatment, and improvement of cognitive decline associated with beta amyloid aggregation.
  • Camphorol 3-O- [2-O ''-(E) -p-coumaroyl] [beta-D-glucopyranosyl- (1 ⁇ 3) -O-alpha-L-ramnopyranosyl- ( 1 ⁇ 6) -O-beta-D-glucopyranoside] was subjected to HRIPT (Human repeated insult patch tests) to determine the cumulative irritation of the skin and to calculate the concentration range that can be used on the skin.
  • test composition the skin composition including an emulsifier, a stabilizer, purified water, etc.
  • the test composition the skin composition including an emulsifier, a stabilizer, purified water, etc.
  • 20 microliters per drop IQ chamber, Epitest Ltd, Finland
  • the skin reactions were examined before and after each patch while performing nine patches three times a week for a total of three weeks.
  • the skin reactions were confirmed up to 48 hours after the final patch removal, and the average response was obtained.
  • the skin response was determined according to the criteria of the International Contact Dermatitis Research Group (ICDRG).
  • “New Material 33” in the table refers to camphorol 3-O- [2-O ''-(E) -p-coumaroyl] [beta-D-glucopyranosyl- (1 ⁇ 3) -O-alpha. -L-lamnopyranosyl- (1 ⁇ 6) -O-beta-D-glucopyranoside]. That is, the substance showed all (-) reactivity in the content range (no subject showed ⁇ , +, ++, or +++ reactivity), through which the substance has no cumulative irritation of the skin, It was found to be safe to use.
  • SH-SY5Y (neuroblastoma, Korea Cell Line Bank) cell line seeded 2X10 6 per well in a 6-well plate (FALCON), and incubated in 37 ° C, 5% CO 2 incubator for 24 hours , GCG 10 ⁇ M, EGCG 10 ⁇ M, existing green tea extract (GTE) 10 ⁇ g / ml, the 'new material 33' 10 ⁇ g / ml, 5-Aza-2'deoxycytidine (5-Aza, Sigma as a positive control) -aldrich) and further incubated for 24 hours by treatment with 1 ⁇ M. Then, the medium was removed and RNA was extracted using an RNA extraction kit (RNeasy mini kit, Quiagen).
  • RNA was synthesized using complementary DNA using a kit (SuperScript VILO cDNA Synthesis Kit, Thermofisher scientific). About 1 ⁇ g of complementary DNA was taken and subjected to real-time quantitative chain polymerization using Taqman probe (Life technology) and Quantitect Probe PCR Kit (Quiagen). Through this, the expression levels of BDNF and DNMT1 were confirmed. At this time, GAPDH, a housekeeping gene, was used as a reference mRNA.
  • novel substance 33 lowers DNMT1 expression and increases BDNF expression, the compound can prevent, prevent, and inhibit neuronal damage or death, thereby protecting neurons and preventing and improving neurodegenerative diseases. You can do it.
  • An injection was prepared in a conventional manner using 50 mg, sterile distilled water titrant for injection, and a pH adjuster titrant for injection.
  • composition ratio of the vitamin and inorganic mixture is a composition that is relatively suitable for health foods, for example, the composition ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method, and then the conventional method. According to the health food composition can be used.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Food Science & Technology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Botany (AREA)
  • Nutrition Science (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Polymers & Plastics (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Molecular Biology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition améliorant le déclin de la fonction cognitive comprenant un nouveau composé séparé du thé post-fermenté, un isomère de celui-ci, un sel de qualité pharmaceutique de celui-ci, un hydrate de celui-ci ou un solvate de celui-ci, la composition pouvant être largement utilisée dans des domaines liés aux fonctions cognitives et à la protection des cellules nerveuses.
PCT/KR2017/011401 2016-10-18 2017-10-16 Composition améliorant la fonction cognitive comprenant un nouveau composé à base de kaempférol dérivé du thé post-fermenté WO2018074793A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CN201780064682.4A CN109843087B (zh) 2016-10-18 2017-10-16 包含新的后发酵茶来源的山奈酚类化合物的认知功能改善组合物
JP2019518490A JP6974450B2 (ja) 2016-10-18 2017-10-16 後発酵茶由来の新規なケンペロール系化合物を含む認知機能改善用組成物
US16/340,753 US20210322452A1 (en) 2016-10-18 2017-10-16 Cognitive function improving composition comprising novel post fermented tea-derived kaempferol-based compound

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2016-0135302 2016-10-18
KR20160135302 2016-10-18
KR10-2017-0119273 2017-09-18
KR1020170119273A KR102394643B1 (ko) 2016-10-18 2017-09-18 후발효차 유래의 신규한 캄페롤계 화합물을 포함하는 인지기능 개선용 조성물

Publications (1)

Publication Number Publication Date
WO2018074793A1 true WO2018074793A1 (fr) 2018-04-26

Family

ID=62018853

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2017/011401 WO2018074793A1 (fr) 2016-10-18 2017-10-16 Composition améliorant la fonction cognitive comprenant un nouveau composé à base de kaempférol dérivé du thé post-fermenté

Country Status (1)

Country Link
WO (1) WO2018074793A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20110110574A (ko) * 2010-04-01 2011-10-07 (주)아모레퍼시픽 학습 능력 증진용 조성물
KR20150047687A (ko) * 2013-10-24 2015-05-06 (주)옴니허브 발효 식물추출물을 유효성분으로 함유하는 기억력 개선 및 증진용 조성물
KR20160026188A (ko) * 2014-08-29 2016-03-09 조현곤 황칠나무잎 발효차 제조방법

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20110110574A (ko) * 2010-04-01 2011-10-07 (주)아모레퍼시픽 학습 능력 증진용 조성물
KR20150047687A (ko) * 2013-10-24 2015-05-06 (주)옴니허브 발효 식물추출물을 유효성분으로 함유하는 기억력 개선 및 증진용 조성물
KR20160026188A (ko) * 2014-08-29 2016-03-09 조현곤 황칠나무잎 발효차 제조방법

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HSIEH, S.-K. ET AL.: "Identification of Biosynthetic Intermediates of Teaghrelins and Teaghrelin-iike Compounds in Oolong Teas, and Their Molecular Docking to the Ghrelin Receptor", JOURNAL OF FOOD AND DRUG ANALYSIS, vol. 23, 2015, pages 660 - 670, XP055477187 *
MANIR, M. M. ET AL.: "Tea Catechins and Flavonoids from the Leaves of Camellia Sinensis Inhibit Yeast Alcohol Dehydrogenase", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 20, 2012, pages 2376 - 2381, XP055477192 *

Similar Documents

Publication Publication Date Title
US11110145B2 (en) Composition for protecting cell from oxidative stress comprising green tea extract which has modified amounts of ingredients
KR102011033B1 (ko) 성분 함량이 변화된 녹차 추출물을 포함하는 인지기능 개선용 조성물
WO2018230906A1 (fr) Composition de blanchiment contenant un nouveau composé à base de quercétine
KR102418100B1 (ko) 신규한 퀘르세틴계 화합물을 포함하는 인지기능 개선용 조성물
WO2018074793A1 (fr) Composition améliorant la fonction cognitive comprenant un nouveau composé à base de kaempférol dérivé du thé post-fermenté
WO2018230909A1 (fr) Composition anti-inflammatoire comprenant un nouveau composé à base de kaempférol dérivé de thé post-fermenté
WO2018074791A1 (fr) Composition améliorant la fonction cognitive comportant un nouveau composé à base de quercétine
WO2019088482A1 (fr) Composition pour améliorer des maladies du système circulatoire, comprenant un extrait de thé ayant un contenu d'ingrédients varié
KR102441381B1 (ko) 3-O-갈로일-3,3',5,5',7-펜타하이드록시플라반(3-O-galloyl-3,3',5,5',7- pentahydroxyflavan)을 포함하는 인지 기능 개선용 조성물
KR20200051452A (ko) 성분 함량이 변화된 녹차 추출물
WO2020096299A1 (fr) Extrait de thé vert ayant une teneur en constituants modifiée et composition le comprenant
WO2018016826A1 (fr) Composition contenant du 3-o-galloyl-3,3',5,5',7-pentahydroxyflavane pour améliorer la fonction cognitive
KR102394643B1 (ko) 후발효차 유래의 신규한 캄페롤계 화합물을 포함하는 인지기능 개선용 조성물
WO2018230908A1 (fr) Composition anti-inflammatoire comprenant un nouveau composé à base de quercétine
WO2018074776A1 (fr) Nouveau composé à base de kaempférol dérivé de thé post-fermenté
WO2018074794A1 (fr) Nouveau composé à base de quercétine
WO2016117762A1 (fr) Composition contenant un extrait de groseille à maquereau ou du glutathion
WO2018230910A1 (fr) Composition de blanchiment comprenant un nouveau composé à base de kaempférol dérivé de thé post-fermenté
KR20190035474A (ko) 성분 함량이 변화된 녹차 추출물을 포함하는 산화스트레스로부터 세포를 보호하기 위한 조성물
WO2018016783A1 (fr) Composition hydratante contenant du 3-o-galloyl-3,3',5,5',7-pentahydroxyflavane
WO2017078353A1 (fr) Composition comprenant stipitalide comme ingrédient actif
WO2017204383A1 (fr) Composition pour inhiber et traiter le cancer chez les femmes, à base d'un extrait de germe de blé et son procédé de production
WO2022102801A1 (fr) Composition destinée à améliorer la capacité cognitive et à prévenir et à traiter la démence et un trouble d'hyperactivité, contenant de l'extrait de galla rhois et de l'ampicilline en tant que principes actifs
WO2018034424A1 (fr) Composition antioxydante ou antivieillissement comprenant du 3-o-galloyl-3,3',5,5',7-pentahydroxyflavane
WO2017003204A1 (fr) Composition neuroprotectrice contenant un extrait de thé post-fermenté

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: 17863057

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2019518490

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17863057

Country of ref document: EP

Kind code of ref document: A1