WO2023120405A1 - アミロイドβの産生抑制及び/又は蓄積抑制用組成物 - Google Patents
アミロイドβの産生抑制及び/又は蓄積抑制用組成物 Download PDFInfo
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- 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
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- A—HUMAN NECESSITIES
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Definitions
- the present invention relates to a composition for suppressing production and/or accumulation of amyloid ⁇ , and the like.
- Amyloid ⁇ (A ⁇ ) is a type of protein produced in the brain. When amyloid ⁇ aggregates to oligomerize or fibrillate, it exhibits neuronal toxicity. In addition, aggregated amyloid ⁇ accumulates without being discharged from the brain, and is thought to trigger the onset of Alzheimer's disease. Therefore, suppressing the production or accumulation of amyloid ⁇ is considered effective, for example, in preventing Alzheimer's disease or in suppressing progression of the disease.
- Acetylcholinesterase inhibitors are known as drugs that improve symptoms of Alzheimer's disease. Inhibition of acetylcholinesterase increases the amount of acetylcholine in the brain and is effective in suppressing the progression of cognitive decline. However, acetylcholinesterase inhibition cannot suppress the production of amyloid ⁇ or remove accumulated amyloid ⁇ . There is a demand for a substance that can be ingested on a daily basis as food or drink, etc., and that can suppress the production or accumulation of amyloid ⁇ .
- Patent Document 1 describes an agent for suppressing and/or improving cognitive function decline containing Cyclo (Gly-Pro).
- An object of the present invention is to provide a composition for suppressing the production and/or accumulation of amyloid ⁇ .
- the present inventors have made intensive studies in view of the above problems, and found that cyclic dipeptides cycloleucylphenylalanine (Cyclo(Leu-Phe)) and cycloleucyllysine (Cyclo(Leu-Lys)) are amyloid ⁇ found to be effective in suppressing the production and/or accumulation of
- the present invention relates to, but is not limited to, the following compositions for suppressing production and/or accumulation of amyloid ⁇ .
- a composition for suppressing the production and/or accumulation of amyloid ⁇ comprising as an active ingredient at least one selected from the group consisting of Cyclo(Leu-Phe), Cyclo(Leu-Lys) and salts thereof.
- the composition of [1] above which suppresses the production and/or accumulation of amyloid ⁇ by inhibiting ⁇ -secretase.
- composition "enhances cognitive function”, “suppresses decline in cognitive function”, “maintains good cognitive function”, “enhances memory”, “suppresses decline in memory”, “improves memory “maintaining good memory”, “improving memory accuracy”, “preventing memory impairment”, “improving memory impairment”, “maintaining memory as a part of cognitive function”, and “preventing memory loss” functions that are suitable for people to become,””improve memory accuracy and judgment accuracy, which are part of cognitive function”, “improve memory retention or consolidation”, “maintain enhanced cognitive function”, “improves executive function”, “promotes attention and concentration”, “improves learning ability”, “maintains and improves orientation”, “delays age-related cognitive decline", “ labeled with one or more functions selected from the group consisting of "strengthening short-term and long-term memory”, “promoting verbal and visuospatial memory” and “maintaining/improving logical thinking ability”
- the composition according to any one of [1] to
- compositions for suppressing the production and/or accumulation of amyloid ⁇ can be provided.
- the composition of the present invention can be used as foods, beverages, pharmaceuticals, etc. for suppressing the production and/or accumulation of amyloid ⁇ .
- FIG. 1 is a graph showing the ⁇ -secretase (BACE) inhibitory activity of the test compound-free group (Control), Cyclo(Leu-Ala) (Comparative Example 1) and Cyclo(Leu-Phe) (Examples 1 to 4).
- FIG. 2 is a graph showing the ⁇ -secretase (BACE) inhibitory activity of the test compound-free group (Control), Cyclo(Leu-Ala) (Comparative Example 1) and Cyclo(Leu-Lys) (Example 5). .
- the composition for suppressing production and/or accumulation of amyloid ⁇ of the present invention contains at least one selected from the group consisting of Cyclo(Leu-Phe), Cyclo(Leu-Lys) and salts thereof.
- the composition for suppressing production and/or accumulation of amyloid ⁇ of the present invention contains at least one selected from the group consisting of Cyclo (Leu-Phe), Cyclo (Leu-Lys) and salts thereof as an active ingredient. .
- the composition for suppressing the production and/or accumulation of amyloid ⁇ of the present invention is sometimes referred to as the composition of the present invention.
- the composition of the present invention is used to suppress the production of amyloid ⁇ and/or the accumulation of amyloid ⁇ .
- Cyclo (Leu-Phe) (cycloleucylphenylalanine) and Cyclo (Leu-Lys) (cycloleucyllysine) used in the present invention are cyclic having a structure in which leucine and phenylalanine, leucine and lysine are condensed, respectively. It is a dipeptide.
- Cyclo(Leu-Phe) and Cyclo(Leu-Lys) are sometimes referred to as CLF and CLK, respectively.
- cyclic dipeptide is characterized by having amino acids as constituent units, and is a diketopiperazine structure produced by dehydration condensation between the amino group of the N-terminal side amino acid and the carboxyl group of the C-terminal side amino acid.
- a compound having In this specification as long as the amino acid constitution of the cyclic dipeptides is the same, it does not matter which order they are listed.
- Leucine represents the same cyclic dipeptide.
- Cyclo(Leu-Lys) and Cyclo(Lys-Leu) (cyclolysylleucine) represent the same cyclic dipeptide.
- Salts of CLF and CLK are not particularly limited as long as they are pharmacologically acceptable salts or salts acceptable for food and drink, and may be either acidic salts or basic salts.
- Acid salts include, for example, inorganic salts such as hydrochlorides, sulfates, nitrates, phosphates; Examples include organic acid salts such as acid salts and propionate salts.
- Examples of basic salts include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; Salts of cyclic dipeptides can be readily prepared by those skilled in the art by any method known in the art.
- CLF, CLK and salts thereof are not particularly limited.
- CLF, CLK or salts thereof can be produced according to known methods.
- CLF, CLK and salts thereof may be derived from natural products, may be artificially synthesized, may be produced by an enzymatic method or a microbial fermentation method, and may be produced by a linear dipeptide. It may be synthesized by dehydration and cyclization.
- protein hydrolysates such as collagen hydrolysates can be heated to obtain heat-treated peptides rich in cyclic dipeptides such as CLF and CLK.
- CLF, CLK and salts thereof may be incorporated into compositions using protein hydrolysates containing them or heat treated products thereof, or concentrates, dry powders or purified protein hydrolysates or heat treated products thereof. Higher degrees may be used and incorporated into the composition.
- the composition of the present invention contains, for example, a protein hydrolyzate or heat-treated product thereof, and CLF, CLK and salts thereof may be part of the protein hydrolyzate or heat-treated product thereof. Commercially available products can also be used for CLF, CLK and salts thereof.
- Amyloid- ⁇ is a peptide sometimes referred to as amyloid- ⁇ protein, amyloid- ⁇ peptide or ⁇ -amyloid.
- Amyloid ⁇ is usually a peptide consisting of around 40 amino acids, and includes amyloid ⁇ 1-42 , amyloid ⁇ 1-40 and the like. Unassociated amyloid- ⁇ is sometimes referred to as amyloid- ⁇ monomer.
- Amyloid ⁇ may form an aggregate with two or more positions.
- Amyloid ⁇ may form, for example, a soluble aggregate (amyloid ⁇ oligomer) in which two or more (eg, 2 to 50) amyloid ⁇ aggregates.
- Amyloid ⁇ oligomers include amyloid ⁇ 1-42 oligomers, amyloid ⁇ 1-40 oligomers, and the like.
- Amyloid ⁇ in the present invention includes non-aggregated amyloid ⁇ and amyloid ⁇ forming aggregates such as oligomers.
- Amyloid ⁇ is produced by the two-step cleavage of amyloid ⁇ precursor protein (APP) by ⁇ -secretase and ⁇ -secretase.
- APP amyloid ⁇ precursor protein
- ⁇ -Secretase is the rate-limiting enzyme for amyloid ⁇ production, and its cleavage regulates the total amyloid ⁇ production. Therefore, by inhibiting ⁇ -secretase, the production of amyloid ⁇ can be suppressed, and the accumulation of amyloid ⁇ can be suppressed.
- CLF, CLK and salts thereof have ⁇ -secretase inhibitory action.
- the composition of the present invention can be used to suppress the production and/or accumulation of amyloid ⁇ by inhibiting ⁇ -secretase.
- CLF, CLK and salts thereof are useful as active ingredients for ⁇ -secretase inhibition.
- the present invention also includes a ⁇ -secretase inhibitory composition containing at least one selected from the group consisting of CLF, CLK and salts thereof.
- the composition of the present invention may contain Cyclo(Leu-Phe) or a salt thereof as an active ingredient.
- the composition of the present invention may contain Cyclo(Leu-Lys) or a salt thereof as an active ingredient.
- composition of the present invention can be used to suppress the production and/or accumulation of amyloid ⁇ in the brain.
- the composition of the present invention can be used to suppress the production and/or accumulation of amyloid ⁇ by inhibiting ⁇ -secretase.
- the composition of the present invention can be used for the prevention or amelioration of a condition or disease associated with amyloid ⁇ accumulation, preferably a condition or disease associated with amyloid ⁇ accumulation in the brain.
- conditions or diseases include conditions or diseases associated with or caused by amyloid- ⁇ accumulation.
- Conditions or diseases associated with or resulting from accumulation of amyloid ⁇ in the brain include, for example, Alzheimer's disease (including Alzheimer's dementia), mild cognitive impairment, and the like.
- the composition of the present invention can be used to prevent or ameliorate the above conditions or diseases, and can be preferably used for the prevention of the above conditions or diseases.
- prevention of a condition or disease includes preventing onset, delaying onset, reducing the rate of onset, reducing risk of onset, and the like.
- Ameliorating a condition or disease includes ameliorating the subject from the condition or disease, alleviating symptoms of the condition or disease, ameliorating symptoms of the condition or disease, slowing progression of the condition or disease, preventing the condition or disease. etc.
- Cognitive function is known to decline in Alzheimer's disease and mild cognitive impairment.
- Symptoms of cognitive decline in Alzheimer's disease and mild cognitive impairment include, for example, memory loss, memory impairment (forgetfulness), aphasia (difficult to name things), apraxia, agnosia (walking in familiar places). (e.g., getting lost), decreased orientation (the ability to correctly recognize one's own situation, such as place, time, name of person, etc.), decreased verbal and non-verbal learning ability, decreased auditory and visual processing, executive function executive dysfunction (inability to plan and do things), decreased ability to concentrate, decreased attention, decreased judgment, decreased spatial awareness, decreased cognitive flexibility, decreased information processing speed, etc.
- a preventive effect on cognitive function decline or an improving effect on cognitive function for example, an effect on preventing or improving the above symptoms can be obtained.
- compositions of the present invention can be applied for either therapeutic use (medical use) or non-therapeutic use (non-medical use).
- Non-therapeutic is a concept that does not involve medical intervention, i.e. human surgery, treatment or diagnosis.
- the composition for suppressing production and/or accumulation of amyloid ⁇ of the present invention can be provided in the form of an agent as an example, but is not limited to this form.
- the agent itself can be provided as a composition, or a composition containing the agent can be provided.
- the composition for suppressing the production and/or accumulation of amyloid ⁇ of the present invention can also be said to be an agent for suppressing the production and/or accumulation of amyloid ⁇ .
- a ⁇ -secretase inhibitory composition can also be referred to as a ⁇ -secretase inhibitor.
- compositions of the invention may be either oral or parenteral.
- the compositions of the invention are preferably oral compositions.
- the composition of the present invention can be in the form of, for example, foods, beverages, pharmaceuticals, quasi-drugs, feeds, etc. Foods, beverages, or pharmaceuticals are preferred.
- the composition of the present invention can also be used by adding it to foods and beverages, pharmaceuticals, quasi-drugs, feeds, and the like.
- the form of the composition of the present invention is not particularly limited, and may be solid (for example, powder, granule, tablet, etc.), liquid, paste, or the like.
- composition of the present invention contains at least one selected from the group consisting of CLF, CLK, and salts thereof, and various diluents, acidulants, acidulants, Antioxidants, stabilizers, preservatives, fragrances, emulsifiers, pigments, seasonings, pH adjusters, nutritional enhancers and the like may be added.
- composition of the present invention when used as a food or drink, at least one selected from the group consisting of CLF, CLK and salts thereof may be added to ingredients that can be used for food and drink (e.g., food materials, if necessary food additives, etc.) can be blended into various foods and drinks.
- Food and drink are not particularly limited, and examples thereof include general food and drink, health food, food with function claims, food for specified health use, health supplement, and food for the sick.
- Health foods, foods with function claims, foods for specified health uses, health supplements, etc. are various formulations such as liquids, fine granules, tablets, granules, powders, capsules, chewable formulations, dry syrups, and liquid diets. Can be used as a form.
- composition of the present invention When the composition of the present invention is used as a drug or quasi-drug, it is added to at least one selected from the group consisting of CLF, CLK and salts thereof, a pharmacologically acceptable carrier, and if necessary It is possible to prepare pharmaceuticals or quasi-drugs in various dosage forms by blending additives and the like. Such carriers, additives, etc. may be those that can be used for pharmaceuticals or quasi-drugs and are pharmacologically acceptable. One or more of antioxidants, coloring agents and the like can be mentioned. Examples of administration (ingestion) forms of pharmaceuticals or quasi-drugs include oral or parenteral (transdermal, transmucosal, enteral, injection, etc.) forms of administration.
- composition of the present invention When used as a drug or quasi-drug, it is preferably an oral drug or oral quasi-drug.
- Dosage forms for oral administration include, for example, liquids, tablets, powders, fine granules, granules, dragees, capsules, suspensions, emulsions, chewables and the like.
- Dosage forms for parenteral administration include, for example, injections, drops, ointments, lotions, patches, suppositories, nasal preparations, pulmonary preparations (inhalants) and the like.
- the pharmaceutical may be a non-human veterinary pharmaceutical.
- Feed also includes feed additives.
- feeds include livestock feeds for cows, pigs, chickens, sheep, horses, etc.; small animal feeds for rabbits, rats, mice, etc.; pet foods for dogs, cats, small birds, etc.;
- the composition of the present invention when used as a food or drink, a drug, a quasi-drug, a feed, etc., the production method is not particularly limited, and at least one selected from the group consisting of CLF, CLK and salts thereof It can be produced by a general method using seeds.
- the composition of the present invention is preferably a liquid composition, more preferably a beverage.
- the beverage may be, for example, a functional beverage.
- the form of the beverage is not particularly limited, and may be a packaged beverage.
- Containers for packaged beverages are not particularly limited, and containers of any shape and material may be used. For example, metal containers such as aluminum cans and steel cans; resin containers such as PET bottles; Containers; glass containers such as glass bottles; and wooden containers such as barrels. Any of commonly used containers can be used.
- a packaged beverage is obtained by filling and sealing such a container with a beverage.
- the total content of CLF, CLK and salts thereof contained in the composition of the present invention is not particularly limited, and can be set according to its form and the like.
- the total content of CLF, CLK and salts thereof in the composition of the present invention may be, for example, 0.00001% by weight or more, preferably 0.0001% by weight or more, and 0.001% by weight. % or more, more preferably 0.01 wt% or more, particularly preferably 0.1 wt% or more, and preferably 50 wt% or less.
- the total content of CLF, CLK and salts thereof may be, for example, 0.00001 to 25% by weight, preferably 0.0001 to 10% by weight, and 0 0.001 to 5% by weight is more preferred, 0.01 to 5% by weight is even more preferred, and 0.1 to 1% by weight is particularly preferred.
- CLF, CLK and salts thereof can be quantified by known methods, for example, liquid chromatography mass spectrometry (LC/MS).
- composition of the present invention contains CLF or a salt thereof
- its content is not particularly limited, but is preferably 0.000001 to 20% by weight, for example. More preferably 0.00001 to 10% by weight, still more preferably 0.0001 to 5% by weight, still more preferably 0.001 to 2% by weight, particularly preferably 0.01 to 1% by weight is.
- CLK or a salt thereof is contained in the composition of the present invention, its content is not particularly limited, but is preferably 0.00001 to 20% by weight, for example. More preferably 0.0001 to 10% by weight, still more preferably 0.001 to 5% by weight, still more preferably 0.01 to 2% by weight, particularly preferably 0.01 to 1% by weight is.
- the composition of the present invention is preferably taken orally (orally administered). There is no particular limitation on the dose (which can also be referred to as intake) of the composition of the present invention.
- the dosage of the composition of the present invention may be an amount that provides an effect of inhibiting the production and/or accumulation of amyloid ⁇ , and may be appropriately set according to the dosage form, administration method, body weight of the subject, and the like. .
- the dosage of the composition of the present invention is preferably such that a ⁇ -secretase inhibitory effect is obtained.
- the dose when the composition of the present invention is ingested or administered to a human (adult) subject, the dose is the total dose of CLF, CLK and salts thereof (converted to cyclic dipeptide) per day It is preferably 0.001 mg or more, more preferably 0.01 mg or more, still more preferably 0.1 mg or more, and preferably 5000 mg or less, more preferably 1000 mg or less, and still more preferably 100 mg or less.
- the total dose of CLF, CLK and salts thereof when the composition of the present invention is ingested or administered to humans (adults), the total dose of CLF, CLK and salts thereof is preferably 0.001 to 5000 mg, more preferably 0.001 to 5000 mg per day. is 0.01 to 1000 mg, more preferably 0.1 to 100 mg.
- the composition of the present invention is an oral composition for ingesting or administering at least one selected from the group consisting of CLF, CLK and salts thereof in the above amount per day per 60 kg body weight to humans. It may be a composition for
- composition of the present invention is preferably taken or administered continuously. It is expected that continuous ingestion or administration of at least one selected from the group consisting of CLF, CLK and salts thereof will result in higher effects.
- the composition of the present invention is preferably taken or administered continuously for one week or longer, more preferably for four weeks or longer, and even more preferably for eight weeks or longer.
- CLF, CLK and salts thereof can be ingested as foods and drinks, and from the viewpoint of safety, long-term ingestion is considered to pose little problem.
- Subjects to whom the composition of the present invention is ingested or administered are not particularly limited. Humans or non-human mammals are preferred, and humans are more preferred.
- the subject to which the composition of the present invention is administered is a subject who needs or desires suppression of amyloid ⁇ production and/or accumulation, and a subject who needs prevention or improvement of a condition or disease associated with amyloid ⁇ accumulation.
- administration subjects in the present invention include middle-aged and elderly people.
- Middle-aged and elderly people include elderly people.
- a middle-aged person may be, for example, a person over the age of 40.
- elderly people are preferred as subjects.
- a senior citizen may be, for example, a human over the age of 60 or over the age of 65.
- the subject of administration of the composition of the present invention may be a healthy subject.
- it can be used in healthy individuals for the purpose of suppressing the production and/or accumulation of amyloid ⁇ in the brain, preventing the accumulation of amyloid ⁇ in the brain, preventing Alzheimer's disease or mild cognitive impairment, and the like.
- composition of the present invention may be labeled with a function exerted by suppressing the production and/or accumulation of amyloid ⁇ .
- indication is also called functionality indication.
- the display is not particularly limited. Such indications include, for example, “increases cognitive function”, “suppresses deterioration of cognitive function”, “maintains good cognitive function”, “improves memory”, “suppresses deterioration of memory”, and “improves memory”.
- the composition of the present invention is preferably a food or drink labeled with one or more of the above labels.
- the above indication may be an indication that the above composition is used to obtain the above functions.
- the label may be attached to the composition itself, or may be attached to the container or packaging of the composition.
- the invention also includes the following methods and uses.
- a method for suppressing production and/or accumulation of amyloid ⁇ comprising administering at least one selected from the group consisting of Cyclo(Leu-Phe), Cyclo(Leu-Lys) and salts thereof.
- a method for inhibiting ⁇ -secretase comprising administering at least one selected from the group consisting of Cyclo(Leu-Phe), Cyclo(Leu-Lys) and salts thereof.
- the method may be a therapeutic method or a non-therapeutic method.
- the use may be therapeutic use or non-therapeutic use.
- Cyclo(Leu-Phe), Cyclo(Leu-Lys), or salts thereof are used to suppress the production and/or accumulation of amyloid ⁇ by inhibiting ⁇ -secretase. be able to.
- At least one selected from the group consisting of CLF, CLK and salts thereof once or more times a day, for example, once to several times (for example, 2 to 3 times) a day preferably ingested or administered to
- the above uses are preferably in humans or non-human mammals, more preferably in humans.
- at least one selected from the group consisting of CLF, CLK, and salts thereof can be used to prevent or improve conditions or diseases associated with amyloid ⁇ accumulation by inhibiting ⁇ -secretase. can.
- the present invention also encompasses a method for preventing or ameliorating a condition or disease associated with amyloid ⁇ accumulation, comprising administering at least one selected from the group consisting of CLF, CLK, and salts thereof.
- At least one selected from the group consisting of CLF, CLK and salts thereof is used in an amount (can also be referred to as an effective amount) capable of suppressing the production and/or accumulation of amyloid ⁇ . do it.
- the effective amount is preferably an amount that provides a ⁇ -secretase inhibitory effect.
- Preferred doses, administration methods, administration subjects, etc. of at least one selected from the group consisting of CLF, CLK and salts thereof are the same as those of the composition of the present invention described above.
- CLF, CLK, or salts thereof may be taken or administered as they are, or may be taken or administered as a composition containing them. For example, a composition of the invention may be ingested or administered.
- At least one selected from the group consisting of CLF, CLK and salts thereof is used for the production of foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc. used for suppressing the production and / or accumulation of amyloid ⁇ .
- the present invention also includes use of at least one selected from the group consisting of CLF, CLK and salts thereof in the production of a composition for suppressing the production and/or accumulation of amyloid ⁇ .
- the present invention also includes the use of CLF, CLK or salts thereof in the manufacture of compositions for inhibiting ⁇ -secretase.
- At least one selected from the group consisting of CLF, CLK and salts thereof can be used for the production of a composition for preventing or improving conditions or diseases associated with amyloid ⁇ accumulation.
- a range represented by “1-2” means from 1 to 2 and includes 1 and 2.
- the upper limit and the lower limit may be any combination of ranges.
- the ⁇ fluorescence intensity of the reaction solution (fluorescence intensity at the end of the reaction (60 minutes) ⁇ fluorescence intensity before the start of the reaction (0 minutes)) was used to evaluate the enzyme activity.
- a group to which no test compound was added was used as a control.
- the inhibitory activity of each test compound was evaluated with the enzyme activity ( ⁇ fluorescence intensity) of Control as 1.
- the BACE activity shown in FIGS. 1 and 2 is a relative value of the BACE activity of the test compound ( ⁇ fluorescence intensity of the reaction solution to which the test compound was added) when the BACE activity of the control ( ⁇ fluorescence intensity of the control) is set to 1. be.
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WO2024095906A1 (ja) * | 2022-11-01 | 2024-05-10 | サントリーホールディングス株式会社 | 神経系細胞の炎症の予防又は抑制用組成物 |
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WO2011055247A1 (en) * | 2009-11-09 | 2011-05-12 | Jawaharlal Nehru Centre For Advanced Scientific Research | A synthetic cyclic dipeptide and a process thereof |
WO2013021353A1 (en) * | 2011-08-11 | 2013-02-14 | Bar-Ilan University | Surface modified proteinaceous spherical particles and uses thereof |
WO2017010537A1 (ja) * | 2015-07-16 | 2017-01-19 | サントリーホールディングス株式会社 | 環状ジペプチド含有血清カルノシン分解酵素阻害用組成物 |
WO2017014121A1 (ja) * | 2015-07-17 | 2017-01-26 | サントリーホールディングス株式会社 | メラニン凝集ホルモン受容体拮抗用組成物 |
WO2017119481A1 (ja) * | 2016-01-08 | 2017-07-13 | サントリーホールディングス株式会社 | 環状ジペプチド含有神経性疾患予防用組成物 |
JP2020196686A (ja) * | 2019-06-04 | 2020-12-10 | ゼライス株式会社 | 認知機能改善用食品 |
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- 2022-12-16 JP JP2023569389A patent/JPWO2023120405A1/ja active Pending
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WO2011055247A1 (en) * | 2009-11-09 | 2011-05-12 | Jawaharlal Nehru Centre For Advanced Scientific Research | A synthetic cyclic dipeptide and a process thereof |
WO2013021353A1 (en) * | 2011-08-11 | 2013-02-14 | Bar-Ilan University | Surface modified proteinaceous spherical particles and uses thereof |
WO2017010537A1 (ja) * | 2015-07-16 | 2017-01-19 | サントリーホールディングス株式会社 | 環状ジペプチド含有血清カルノシン分解酵素阻害用組成物 |
WO2017014121A1 (ja) * | 2015-07-17 | 2017-01-26 | サントリーホールディングス株式会社 | メラニン凝集ホルモン受容体拮抗用組成物 |
WO2017119481A1 (ja) * | 2016-01-08 | 2017-07-13 | サントリーホールディングス株式会社 | 環状ジペプチド含有神経性疾患予防用組成物 |
JP2020196686A (ja) * | 2019-06-04 | 2020-12-10 | ゼライス株式会社 | 認知機能改善用食品 |
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WO2024095906A1 (ja) * | 2022-11-01 | 2024-05-10 | サントリーホールディングス株式会社 | 神経系細胞の炎症の予防又は抑制用組成物 |
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