CN109562131A - Composition - Google Patents
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- CN109562131A CN109562131A CN201880000676.7A CN201880000676A CN109562131A CN 109562131 A CN109562131 A CN 109562131A CN 201880000676 A CN201880000676 A CN 201880000676A CN 109562131 A CN109562131 A CN 109562131A
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- composition
- powder
- disease
- brain
- earthworm
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- 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
-
- 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
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- 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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The composition of volume as the composition of the atrophy for improving the hippocampus being located in human brain, for increasing the hippocampus in the human brain or the composition of the volume for increasing human brain, using Co-Q10 and dry earthworm powder as effective component.Co-Q10 is reduced coenzyme Q 10.Thus it can provide and can be used in that A Zihaimoshi disease, dementia, Parkinson's disease, myalgic brain ridge Marrow be scorching and the composition of the prevention or treatment of the composition of prevention or/and the treatment of disease related with brain such as multi-system atrophy, particularly the atrophy that can be used in the hippocampus being located in brain.
Description
Technical field
The present invention relates to the composition of people's intake or it is applied to the composition of people.
Background technique
In the past, there are A Zihaimoshi disease, dementia, Parkinson's disease, myalgic brain ridge Marrow inflammation and multi-system atrophies
Deng the various diseases such as disease relevant to brain or the disease relevant with blood vessel such as veins of lower extremity tumor and deep vein thrombosis, just
It is studied to the medicine for preventing or treating these diseases.
For example, the cerebral diseases such as A Zihaimoshi disease are greatly increased with aging, become need to cope with it is worldwide strong
Kang Wenti.About A Zihaimoshi disease, propose the preventing/treating agent of amnesia (referring to patent document 1).In patent text
Offer described in 1 using selected from least one of carnosic acid and Rosmarinic acid or the permissible salt of its physiology as effectively at
The preventing/treating agent for the amnesia divided, and show the experimental result using mouse.
However, it is desirable to the higher medicine of human effectiveness.
Existing technical literature
Patent document
Patent document 1: Japanese Unexamined Patent Publication 2006-199666 bulletin
Summary of the invention
Problems to be solved by the invention
In view of the above problems, the purpose of the present invention is to provide the prevention that can be used in disease appropriate or/and treatments
Composition.
Means for solving the problems
It is a feature of the present invention that it is a kind of for improving the composition of the atrophy for the hippocampus being located in human brain, with
Co-Q10 and dry earthworm powder are as effective component.
The effect of invention
According to the present invention, it is possible to provide the composition of a kind of prevention that can be used in disease or/and treatment.
Detailed description of the invention
Fig. 1 is the explanatory diagram of the MRI image based on horizontal section of the brain of the A Zihaimoshi patient before administration.
Fig. 2 is the explanatory diagram of the MRI image based on horizontal section of the brain of the A Zihaimoshi patient after administration.
Specific embodiment
The present inventor has made intensive studies the application of Co-Q10.Wherein have studied disease relevant to brain or with
The prevention or the application in treatment of the relevant disease of blood vessel.The starting point herein is, although the morbidity of A Zihaimoshi disease is former
Because not necessarily clear, but the activity reduction of mitochondria is considered being also one of its reason.
In the biosynthesis of atriphos (ATP) for being referred to as " energy currency of organism ", it is related to glycolysis system
This 3 kinds of systems of system, tricarboxylic acid cycle, electron transport system.Mitochondria and tricarboxylic acid cycle and electron transport system have very high point
System.Therefore, the activity of mitochondria is very important maintenance, the activity of life.As the activity reduction for making mitochondria
Main cause can enumerate the reduction of reduced coenzyme Q 10.
Mitochondria be often exposed to because of active oxygen species caused by oxidative stress in, but antioxidant can protected from
The damage of oxidative stress.On the other hand, reduced coenzyme Q 10 is the constituent of electron transport system, while being also anti-oxidant
Substance.Result, it is believed that antioxidant activity reduces, dysfunction occurs for mitochondria, while electricity if reduced coenzyme Q 10 is reduced
The efficiency of sub- transmission system reduces, the biosynthesis activity of ATP reduces.
There is report to point out, in the dog of dementia, the Co-Q10 of intracerebral is reduced, the activity drop of relative mitochondria
It is low.In addition, also describing in patent document 1, by using the experiment of mouse, preventing/treating of the Co-Q10 as amnesia
Agent is effective.These record etc. imply that mitochondria activity reduce or intracerebral Co-Q10 reduction and A Zihaimoshi disease
Etc. cerebral diseases relevance, expect Co-Q10 for the cerebral diseases such as A Zihaimoshi disease preventing/treating effect.
But although implying that validity (referring to patent document 1) in animal experiments, also there is research report to refer to
Out, in Human clinical's research, CoQ10 does not show special improvement to Parkinson's disease
(Parkinson study group QE3investigators, 2014), Co-Q10 is not necessarily clear to the effect of cerebral disease,
Also validity when Co-Q10 is used alone not is shown.
It can be seen that status is for capableing of preventing/treating disease relevant to brain and disease relevant with blood vessel etc.
Composition remains a need for.
The inventors discovered that in plurality of raw materials substance, containing Co-Q10 and when the raw material of earthworm source, for brain phase
It the improvement of the disease of pass, the improvement of disease relevant to blood vessel, particularly works for the recovery of the hippocampus of atrophy, especially tests
It is demonstrate,proved as the prophylactic of atrophy of hippocampal or the validity of therapeutic agent, so as to complete the present invention.
Hereinafter, as an embodiment of the invention, for containing Co-Q10 (coenzyme Q10) and earthworm source
The composition of raw material is illustrated.
Any one of reduced coenzyme Q 10 (ubiquinol) and CoQ10 (ubiquinone) can be used in Co-Q10,
But it is preferred that reduced coenzyme Q 10.Both Co-Q10s are mutually changed by redox reaction.Reduced coenzyme Q 10 be
Biosynthesis in organism, and it is active.Reduced coenzyme Q 10 starts to carry out industrial manufacture in recent years, can be oral
Intake.On the other hand, CoQ10 mainly passes through food or the industrial replenishers manufactured or drug oral uptake to life
In object.After the CoQ10 absorbed is absorbed in intestinal tube, it is transformed into reduced coenzyme Q 10 and is utilized.Cause
This, the Co-Q10 contained in composition of the invention is preferably reduced coenzyme Q 10, but may be CoQ10.
Co-Q10 can be raw medicine powder, be also possible to processed goods.Processed goods has the product of powder morphology and liquid, but
It is not limited to these.Co-Q10 used in present embodiment is preferably powder morphology.
The content for the Co-Q10 (especially reduced coenzyme Q 10) for including in the composition of 1 consumption per day needs to have for treatment
Effect amount can be 50mg~800mg, be preferably in terms of the amount (100%) of Co-Q10 (especially reduced coenzyme Q 10) itself
80mg~500mg, more preferably 100mg~300mg.Furthermore, the content for the Co-Q10 for including in composition is preferably
200mg~300mg, in order to be easy adjust dose, more preferably 100mg~200mg, for the patient of serious symptom, preferably
For 300mg~500mg.The therapeutically effective amount of Co-Q10 (especially reduced coenzyme Q 10) refers in order to even slightly press down
System restores 1 consumption per day required for mitochondrial obstacle.
Earthworm source raw material can be obtained for dry earthworm powder, the extract of earthworm or extract of earthworm etc. by earthworm
Raw material.Dry earthworm powder (including earthworm freeze-dried powder) can be raw medicine powder or processed goods.Processed goods
Have and extract powder, extracting powder, but is not limited to these.
Earthworm freeze-dried powder be with earthworm (especially American-European original bloodworm) for raw material is freeze-dried and
Obtained powder.Earthworm freeze-dried powder, which has, is transformed into fibrinolysin for the plasminogen (plasminogen) in blood
(plasmin) effect for showing the effect of Hyperfibrinolysis and directly dissolving the fibrin for participating in blood clotting.
It is thus known that earthworm freeze-dried powder is for disease relevant to blood vessel, i.e. cerebral infarction, ischemic cerebrovascular disorder, glycosuria
Disease, the treatment of vascular hypertension, the prevention of thrombosis, the increase of fibrinolysin (fibrinogenase) and platelet aggregation rate
Increased inhibition is effective.It should be noted that earthworm freeze-dried powder includes the egg extracted from edible bloodworm
White catabolic enzyme, with the strong characteristic of fibrinous dissolution activity.
The LR powder I (LR powder 1) of applicant's sale, LR powder II (LR powder can be used in the earthworm freeze-dried powder
End 2), the product of LR powder III (LR powder 3) or other companies, preferably LR powder III (LR powder 3).
The content for the earthworm source raw material (especially earthworm freeze-dried powder) for including in composition needs to have for treatment
Effect amount can be 10mg~200mg, preferably 10mg~100mg, more preferably 20mg~80mg.Furthermore, composition
In include the content of earthworm source raw material (especially earthworm freeze-dried powder) be preferably 60mg~100mg, in order to be easy
Adjust dose, more preferably 10mg~50mg, for the patient of serious symptom, preferably 100mg~200mg.It needs to illustrate
, the therapeutically effective amount of earthworm source raw material (especially earthworm freeze-dried powder) refers to be partly dissolved needed for thrombus
1 consumption per day wanted.
The ratio for the earthworm source raw material (especially earthworm freeze-dried powder) for including in composition can for 0.1 times~
1.5 times, preferably 0.3 times~1 times (equivalent), further preferably 0.4 times~0.7 times, be suitably 0.5 times or so.In other words,
The ratio for the earthworm source raw material (especially earthworm freeze-dried powder) for including in composition can be with relative to the amount of Co-Q10
It is 0.1 times~4 times, preferably 0.2 times~3 times, more preferably 0.4 times~2 times.
The form of composition can be selected from soft capsule, hard capsule, tabletting, powder, particle, beverage etc..It is preferred that flexible glue
The form of capsule, powder, particle, the form of more preferable soft capsule.For example, the composition of powder morphology can be blended in tube feed battalion
Feeding agent is medium so that composition is included in inbutation feeding agent.As a result, even with the patient for being difficult to oral uptake, also can
Apply composition.
It in the composition, can also include vitamin, minerals, carbon water other than Co-Q10 and earthworm source raw material
The nutrients such as compound, lipid and/or antioxidant and/or supplement agent material etc. are useful for maintenance/improvement of health
Material.
The processing carried out to composition is not particularly limited, and can be the processing appropriate such as food, replenishers or drug.
For example, composition can be handled according to the suggestion of doctor as replenishers.
Composition is effective for the prevention or treatment of disease related with brain (the especially disease of atrophy of hippocampal etc), makees
It is functioned for the pharmaceutical composition of such disease, medicine, preventive medicine or treatment/prevention with composition.As object
Disease related with brain include that A Zihaimoshi disease, dementia, Parkinson's disease, myalgic brain ridge Marrow be scorching and multi-system atrophy
Disease etc., but it is not limited to these.In addition, composition is also effective for the prevention or treatment of disease related with blood vessel, as this
Pharmaceutical composition, medicine, preventive medicine or the treatment/prevention of the disease of sample are functioned with composition.As object with
The related disease of blood vessel includes veins of lower extremity tumor or deep vein thrombosis, but is not limited to these.
The embodiment of the present invention is illustrated below.
Embodiment 1
<hard capsule>
As the embodiment 1 of composition of the invention, following preparation is hard containing Co-Q10 and earthworm freeze-dried powder
Capsule.That is, will comprising reduced coenzyme Q 10 stabilize powder (Kaneka Co. Ltd. system: reduced coenzyme Q 10 P30) and
Each composite material of earthworm freeze-dried powder (Hui Long Co., Ltd system: LR powder III) is mixed with common powder mixer
Afterwards, it is fitted into hard capsule and hard capsule (preparation) is made.It should be noted that reduced coenzyme Q 10 stabilizes powder (P30) table
Show the powder of the reduced coenzyme Q 10 containing 30%, if such as reduced coenzyme Q 10 to stabilize powder be 180mg, it is contained
Reduced coenzyme Q 10 be 60mg.
The component amount of each composite material in 1 capsule are as follows: reduced coenzyme Q 10 stabilizes powder (P30) 180mg (its
In, reduced coenzyme Q 10 60mg), earthworm freeze-dried powder (LR powder III) 30mg, food yeast (zinc, copper, selenium ferment
It is female) 10mg, vitamin B1 10mg, vitamin B2 5mg, vitamin B6 5mg, vitamin B12 20mg, folic acid 0.1mg, dimension life
Plain D3 0.6mg, excipient 89.3mg.
Embodiment 2
<powder>
As the embodiment 2 of composition of the invention, following preparation is dissipated containing Co-Q10 and earthworm freeze-dried powder
Agent.That is, each ingredient of powder (P30) and earthworm freeze-dried powder (LR powder III) will be stabilized comprising reduced coenzyme Q 10
After material is mixed with common powder mixer, powder (preparation) is made.
The component amount of each composite material in 1 bag are as follows: (wherein, also reduced coenzyme Q 10 stabilizes powder (P30) 360mg
Prototype Co-Q10 is 120mg), earthworm freeze-dried powder (LR powder III) 60mg, food yeast (zinc, copper, selenium yeast)
20mg, vitamin B1 20mg, vitamin B2 10mg, vitamin B6 10mg, vitamin B12 40mg, folic acid 0.2mg, dimension life
Plain D3 1.2mg, excipient 120.6mg.
Embodiment 3
<soft capsule>
As the embodiment 3 of composition of the invention, following preparation is soft containing Co-Q10 and earthworm freeze-dried powder
Capsule.That is, each of powder (P30) and earthworm freeze-dried powder (LR powder III) will be stabilized comprising reduced coenzyme Q 10
After composite material is mixed with common soft capsule with mixing machine, capsule filling is carried out, soft capsule (preparation) is made.
The component amount of each composite material in 1 capsule are as follows: reduced coenzyme Q 10 stabilizes powder (P30) 50mg (its
In, reduced coenzyme Q 10 is about 16.67mg), Mihara Rubellus powder (Mihara Rubellus system) 30mg, dimension life
Plain E 10mg, rapeseed oil 139.7mg, Poem DO-100V (manufacture of Li Yan vitamin company) 70mg, soybean lecithin 0.3mg.
It should be noted that Mihara Rubellus powder is the dry earthworm powder of Mihara Rubellus manufacture.
<improvement of disease>
By absorbing any one of the composition (hard capsule, powder, soft capsule) of Examples 1 to 3, observed
The improvement of the symptom of the cerebral diseases patient such as A Zihaimoshi disease including dementia, the symptom of veins of lower extremity tumor patient change
The improvement of kind, Deep venou tumor patient symptom.As specific improvement example, withering to the hippocampus in A Zihaimoshi disease is shown
The improvement example of contracting.
For being diagnosed as 2 patients of A Zihaimoshi disease, by the preparation prepared in<embodiment 1>with daily 4 glue
Capsule is administered 3 months.Before the confirmation of clinical effectiveness is by using brain image analysis software VBM Tutorial (SPM8) analysis administration
The MRI image of the brain shot afterwards carries out.
Fig. 1 is that the patient A of one of patient (is diagnosed as the severe A Zihaimoshi disease decomposed with moderate hippocampus
82 years old male) horizontal section near cerebral hippocampal before administration MRI image.Fig. 2 is the brain of patient A upon administration
Hippocampus near horizontal section MRI image.By the MRI image it has been confirmed that compared with before administration, hippocampus increases after administration
Greatly.
It is confirmed using the result that SPM8 is analyzed, compared with before administration, the appearance of the cerebral hippocampal of 2 patients after administration
Product increases 12%~9%.Thus it shows, the preparation (hard capsule) prepared in embodiment 1 is for improving A Zihaimoshi
The atrophy of the cerebral hippocampal of patient is effective.
It should be noted that can be other various embodiments the present invention is not limited to present embodiment.
Industrial applicibility
The present invention can be used in the fields such as drug, replenishers or food.
Claims (5)
1. it is a kind of for improving the composition of the atrophy for the hippocampus being located in human brain, made with Co-Q10 and dry earthworm powder
For effective component.
2. it is a kind of for increasing the composition of the volume for the hippocampus being located in human brain, made with Co-Q10 and dry earthworm powder
For effective component.
3. a kind of for increasing the composition of the volume of human brain, using Co-Q10 and dry earthworm powder as effective component.
4. it is a kind of for improving the composition of the atrophy of the hippocampus of brain, containing Co-Q10 and dry earthworm powder, the coenzyme
Q10 is reduced coenzyme Q 10.
5. it is a kind of for increasing the composition of the volume of the hippocampus of brain, containing Co-Q10 and dry earthworm powder, the coenzyme
Q10 is reduced coenzyme Q 10.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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JP2017-139099 | 2017-07-18 | ||
JP2017139099A JP6253837B1 (en) | 2017-07-18 | 2017-07-18 | Composition |
PCT/JP2018/005201 WO2019016988A1 (en) | 2017-07-18 | 2018-02-15 | Composition |
Publications (1)
Publication Number | Publication Date |
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CN109562131A true CN109562131A (en) | 2019-04-02 |
Family
ID=60860165
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN201880000676.7A Pending CN109562131A (en) | 2017-07-18 | 2018-02-15 | Composition |
Country Status (4)
Country | Link |
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JP (1) | JP6253837B1 (en) |
CN (1) | CN109562131A (en) |
TW (1) | TW201907948A (en) |
WO (1) | WO2019016988A1 (en) |
Families Citing this family (1)
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TW201929877A (en) * | 2017-12-29 | 2019-08-01 | 大江生醫股份有限公司 | Use of earthworm extracts for preparing a pharmaceutical composition for protection of brain neurons |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2017014162A1 (en) * | 2015-07-21 | 2017-01-26 | Well Stone 有限会社 | Amyloid β fibril-decomposing agent, therapeutic/prophylactic agent for disease associated with amyloid β fibrillogenesis, and food composition for treating/preventing disease associated with amyloid β fibrillogenesis |
Family Cites Families (4)
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KR900012617A (en) * | 1987-10-28 | 1990-09-01 | 요오이찌 이시이 | Thrombotic cure and its manufacturing method |
JP2732109B2 (en) * | 1989-02-10 | 1998-03-25 | 正樹 今川 | Dementia treatment |
JP2005328803A (en) * | 2004-05-21 | 2005-12-02 | Towa Kagaku Kk | Vitality-promoting and aging-preventing food and method for producing the same |
EP3097918B1 (en) * | 2014-01-20 | 2019-04-03 | Well Stone Co. | Catecholamine production accelerator, and therapeutic and preventive agent and therapeutic and preventive food composition for diseases caused by catecholamine deficiency |
-
2017
- 2017-07-18 JP JP2017139099A patent/JP6253837B1/en active Active
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2018
- 2018-02-15 CN CN201880000676.7A patent/CN109562131A/en active Pending
- 2018-02-15 WO PCT/JP2018/005201 patent/WO2019016988A1/en active Application Filing
- 2018-03-15 TW TW107108820A patent/TW201907948A/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017014162A1 (en) * | 2015-07-21 | 2017-01-26 | Well Stone 有限会社 | Amyloid β fibril-decomposing agent, therapeutic/prophylactic agent for disease associated with amyloid β fibrillogenesis, and food composition for treating/preventing disease associated with amyloid β fibrillogenesis |
Non-Patent Citations (1)
Title |
---|
LI, G. ET AL: "Diet supplement CoQI0 delays brain atrophy in aged transgenic mice with mutations in the amyloid precursor protein: An in vivo volume MRI study", 《BIO FACTORS》 * |
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Publication number | Publication date |
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WO2019016988A1 (en) | 2019-01-24 |
JP6253837B1 (en) | 2017-12-27 |
JP2019019084A (en) | 2019-02-07 |
TW201907948A (en) | 2019-03-01 |
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