WO2017007099A1 - G단백질 결합형 수용체19 작용제를 유효성분으로 함유하는 알츠하이머 질환 또는 치매를 예방, 치료 또는 지연하기 위한 약학적 조성물 - Google Patents
G단백질 결합형 수용체19 작용제를 유효성분으로 함유하는 알츠하이머 질환 또는 치매를 예방, 치료 또는 지연하기 위한 약학적 조성물 Download PDFInfo
- Publication number
- WO2017007099A1 WO2017007099A1 PCT/KR2016/000447 KR2016000447W WO2017007099A1 WO 2017007099 A1 WO2017007099 A1 WO 2017007099A1 KR 2016000447 W KR2016000447 W KR 2016000447W WO 2017007099 A1 WO2017007099 A1 WO 2017007099A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dementia
- disease
- alzheimer
- protein
- coupled receptor
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention provides a method for preventing, treating or delaying Alzheimer's disease (AD) or dementia containing a G protein-coupled receptor 19 (GPCR19) agonist or a pharmaceutically acceptable salt thereof as an active ingredient.
- AD Alzheimer's disease
- a ⁇ deposition in Alzheimer's disease is detrimental to neurons and stromal cells in the brain, resulting in brain inflammation and neuronal death, which are characteristic features of Alzheimer's disease.
- Many different theories have been developed on the pathogenesis of AD, and one of the well-established theories suggests the association of cholinergic pathways, which leads to a gradual decrease in the neurotransmitter acetylcholine as the ultimate development of AD.
- AD also pathologies the deposition of A ⁇ and tau-associated neurofibrillary tangles commonly associated with oxidative stress conditions such as exposure to peroxynitrite (ONOO ⁇ ) and superoxide ions ( ⁇ O 2 ⁇ ). It is characterized by enemy.
- ONOO ⁇ peroxynitrite
- ⁇ O 2 ⁇ superoxide ions
- Alzheimer's disease is divided into familial AD caused by genetic factors and sporadic AD that occurs in a large number of patients, although the exact cause is unknown.
- Human AD patients show complex cognitive deficits by showing psychological symptoms such as memory loss and psychosomatic abnormalities including increased anxiety and hypersensitivity.
- Senile plaque and neurofibrillary tangles are pathological features in the brains of patients who die from AD.
- the senile plaque is formed by accumulation of proteins and dead cells, etc. outside the cell, and its main component is a peptide called amyloid-beta (A ⁇ ).
- a ⁇ amyloid precursor protein
- APP amyloid precursor protein
- BSCE ⁇ -secretase
- AD treatments used in various countries are mostly ACh degrading enzyme inhibitors, such as tacrine and aricept.
- pharmaceutical companies such as Merck and Bayer are bringing similar drugs to market.
- tacrine the side effects of hepatotoxicity are large, and treatment is often stopped.
- aricept is said to have less side effects.
- nicotine receptor inhibitor ABT-418 muscarinic receptor inhibitor zanomeline, acetylcholine precursor lecithin, acetyl-L-carnitine, metal chelator desperioxamine, rioquinol, beta-sheet breaker iA ⁇ 5, iA ⁇ 11, Antioxidants Vitamin E, Ginkgo Biloba extract, Melatonin, Idebenone, sAPP release nicotine, acetylcholine, carbacol, beta secretase or gamma secretase inhibitors OM99-1, OM99-2, OM99-3, Z-VLL -CHO, NSAIDs, an anti-inflammatory drug, have been developed, but the effects are still small enough to alleviate or slow the progression of some pathological symptoms, or due to their toxicity, most of them are difficult to apply due to their toxicity. Development is urgent.
- the inventors of the present invention have found that a composition comprising sodium taurodeoxycholate, a GPCR19 agonist, and derivatives thereof is effective in Alzheimer's disease or dementia, and prevents, treats, ameliorates, or delays Alzheimer's disease or dementia. It is proposed as a component. To date, no attempt has been made to improve or treat Alzheimer's disease or dementia with a composition comprising sodium taurodioxycholate and its derivatives, and no reports have been reported on the therapeutic effects of Alzheimer's disease or dementia.
- the present invention provides a pharmaceutical composition for preventing, treating or delaying Alzheimer's disease or dementia containing a GPCR19 agent as an active ingredient, or specifically, sodium taurodeoxycholate and its derivatives are effective.
- a pharmaceutical composition for preventing, treating or delaying Alzheimer's disease or dementia, which is included as an ingredient, is provided, and the pharmaceutical composition may be formulated in the form of injectables and oral preparations, in which a pharmaceutically acceptable additive is further added. May be included.
- G protein-coupled receptor 19 (GPCR19) agonist when administered to a subject, does not harm the subject's health, exhibits the effect of improving cognitive and behavioral disorders, and apoptosis of brain tissue It may be effective in preventing Alzheimer's disease or dementia, or by delaying or treating disease in individuals who have already developed the disease by inhibiting the disease, enhancing immunity, and reducing the formation of amyloid ⁇ (A ⁇ ) plaques.
- GPCR19 G protein-coupled receptor 19
- Figure 1 shows the results of measuring the weight change of the mice after a total of 20 injections of PBS or sodium taurodioxycholate (1 mg / kg) twice a week to the control and Alzheimer's mice.
- Figure 2 shows the results of evaluating the spatial learning ability by performing a labyrinth of water after a total of 20 injections of PBS or sodium taurodioxycholate (1 mg / kg) twice a week to the control and Alzheimer's mouse.
- FIG. 3 shows representative images of mouse behavior patterns in a tank with a platform removed after a total of 20 injections of PBS or sodium taurodioxycholate (1 mg / kg) twice a week in the control and Alzheimer's mice. .
- FIG. 4 crosses the platform position in mouse behavior patterns in a bath in which the platform was removed after a total of 20 injections of PBS or sodium taurodioxycholate (1 mg / kg) twice a week in control and Alzheimer's mice. ) Shows the result of measuring the number of times and the time spent in the platform position.
- amyloid ⁇ that causes inflammation in the prefrontal cortex and hippocampal tissue of the mouse after injection of PBS or sodium taurodioxycholate (1 mg / kg) twice a week in a control group and Alzheimer's mouse twice a week. Fluorescent staining of (A ⁇ ) plaques and microglia and astrosites that cause inflammatory reactions is shown.
- FIG. 7 shows iNOS producing cytosolic cytotoxicity in the prefrontal cortex of the mouse after 20 injections of PBS or sodium taurodioxycholate (1 mg / kg) twice a week in the control and Alzheimer's mice. The results are shown by fluorescein expression.
- Figure 8 shows the brain tissue of Alzheimer's model mice to which the drug was administered, and shows the result of fluorescence staining of the apoptosis in the frontal cortex and hippocampal region.
- Figure 9 shows the results of analysis of the inflammatory substances in the blood after the injection of PBS or sodium taurodioxycholate (1 mg / kg) twice a week a total of 20 control mice and Alzheimer's mice twice a week .
- the present invention is for preventing, treating or delaying Alzheimer's disease (AD) or dementia containing a G protein-coupled receptor 19 (GPCR19) agonist or a pharmaceutically acceptable salt thereof as an active ingredient. It relates to a pharmaceutical composition.
- AD Alzheimer's disease
- GPCR19 G protein-coupled receptor 19
- the G protein-coupled receptor 19 (GPCR19) agonist is sodium taurodeoxycholate.
- the pharmaceutical composition may be formulated in the form of preparations for oral, rectal, intravenous, intramuscular, intraperitoneal, subcutaneous, nasal administration.
- the pharmaceutical composition is composed of tablets, pills, powders, granules, capsules, suspensions, liquid solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, suppositories, and injections. It can have any formulation selected from the group.
- the route of administration of the composition may be administered via any general route as long as it can reach the desired tissue.
- the composition of the present invention may be administered orally, rectally, intravenously, intramuscularly, intraperitoneally, subcutaneously, or intranasally, as desired.
- the composition may also be administered by any device in which the active agent may migrate to the target cell.
- the pharmaceutical preparations for oral administration may be in dosage unit form and ampoules, for example dragees, tablets, pills, powders, granules or capsules. They are prepared by methods known per se, for example by conventional mixing, granulation, preparation of sugars, dissolution or lyophilization.
- pharmaceutical preparations for oral administration are prepared by mixing the active ingredient with a solid carrier, granulating the mixture and, if necessary, adding the appropriate additives, and then formulating the mixture or granules in the form of tablets or dragees. Can be.
- Suitable carriers are in particular fillers such as sugars such as lactose, saccharose, mannitol or sorbitol, cellulose preparations and / or calcium phosphates such as tricalcium phosphate or calcium hydrogen phosphate, and binders such as corn, Starch paste using wheat, rice or potato starch, gelatin, tragacanth, methylcellulose and / or polyvinylpyrrolidone, and if necessary disintegrating agents such as the starches mentioned above, carboxymethyl starch, crosslinked polyvinylpyrrolidone Money, agar or alginic acid or salts thereof such as sodium alginate.
- fillers such as sugars such as lactose, saccharose, mannitol or sorbitol, cellulose preparations and / or calcium phosphates such as tricalcium phosphate or calcium hydrogen phosphate
- binders such as corn, Starch paste using wheat, rice or potato starch, gelatin, tragacanth, methylcellulose
- Additives are in particular flow-controlling agents and lubricants, for example silicic acid, talc, stearic acid or salts thereof such as magnesium stearate or calcium, and / or polyethylene glycol.
- a concentrated sugar solution which provides a dragee core with a suitable coating that may be resistant to gastric juice, and optionally contains gum arabic, talc, polyvinylpyrrolidone, polyethylene glycol and / or titanium dioxide in a suitable organic solvent or solvent mixture, Alternatively, a lacquer solution may be used, or a solution of a suitable cellulose preparation such as acetylcellulose phthalate or hydroxypropylmethylcellulose phthalate may be used to form a coating resistant to gastric juice.
- Other orally administrable pharmaceutical preparations include capsules, dry-filled capsules made of gelatin, and soft sealed capsules made of gelatin and plasticizers such as glycerol or sorbitol.
- Dry-filled capsules contain the active ingredient in the form of particles, for example in the form of fillers such as lactose, binders such as starch, and / or glidants such as talc or magnesium stearate, and, if appropriate, stabilizers. You may.
- the active ingredient may be dissolved or suspended in suitable liquids such as fatty oils, paraffin oils or liquid polyethylene glycols, and stabilizers may be added thereto.
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
- Parenteral preparations can be effective injections in several ways, such as intravenous, intraarterial, intramuscular, intraperitoneal, intranasal, intradermal, subcutaneous, preferably intravenous.
- Such liquids are preferably isotonic aqueous solutions or suspensions which may be prepared before use from lyophilized preparations containing the active ingredient alone or in combination with a pharmaceutically acceptable carrier.
- the pharmaceutical preparations may be sterilized and / or may contain additives such as preservatives, stabilizers, wetting and / or emulsifiers, solubilizers, salts for adjusting the osmotic pressure and / or buffers.
- non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like may be used.
- injectable ester such as ethyl oleate, and the like
- base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
- the G protein-coupled receptor 19 (GPCR19) agonist or a pharmaceutically acceptable salt thereof includes cerebral amyloid angiopathy, a disorder associated with cognitive impairment, mild cognitive impairment, attention deficit symptoms associated with Alzheimer's disease,
- the disease is selected from the group consisting of neurodegeneration, degenerative dementia, elderly dementia, senile dementia, cerebrovascular dementia, alcoholic dementia, dementia associated with Parkinson's disease, amyloid ⁇ -related conditions that are dementia associated with Parkinson's disease, and degeneration of the cortical basal ganglia Prevention, treatment or delay.
- the G protein-coupled receptor 19 (GPCR19) agonist or pharmaceutically acceptable salt thereof is in an amount of 0.1 mg / kg / day to 1000 mg / kg / day, specifically 1 mg / kg / day An amount of from 500 mg / kg / day, more specifically 10 mg / kg / day to 100 mg / kg / day, may be administered to a 75 kg body weight warm-blooded animal to prevent or treat Alzheimer's disease or dementia.
- the G protein-coupled receptor 19 (GPCR19) agonist or pharmaceutically acceptable salt thereof is administered at a dosage interval of once to three times a week, specifically, once to two times a week. Can be.
- the dosage and interval of administration of the G protein-coupled receptor 19 agonist for use in the present invention can vary depending on various factors, such as the effectiveness and duration of action of the active ingredient, the mode of administration, the severity of the sex, age, weight and other diseases of the warm-blooded animal. It may vary depending on individual conditions such as.
- the particular route of administration and dosage may be selected by the attending physician / veterinarian according to the characteristics of the subject to be administered, such as age, weight, disease state, physical condition, and the like.
- the invention is also a formulation in the form of a combination of a G protein-binding receptor 19 (GPCR19) agonist or a pharmaceutically acceptable salt thereof and at least one drug selected from the group consisting of cognitive enhancers, memory enhancers and choline esterase inhibitors.
- GPCR19 G protein-binding receptor 19
- the G protein-coupled receptor 19 agonist according to the present invention may be administered in combination / combination with other drugs for the prevention, treatment or delay of Alzheimer's disease or dementia.
- the present invention therefore also encompasses methods of treating Alzheimer's disease or dementia patients, including combination therapy with G protein coupled receptor 19 agonists and different Alzheimer's disease or dementia prevention / treatment agents.
- the present invention provides a food composition for preventing, improving or delaying Alzheimer's disease (AD) or dementia containing a G protein-coupled receptor 19 (GPCR19) agonist or a pharmaceutically acceptable salt thereof. It is about.
- AD Alzheimer's disease
- GPCR19 G protein-coupled receptor 19
- the G protein-coupled receptor 19 (GPCR19) agonist is sodium taurodeoxycholate.
- the G protein-coupled receptor 19 (GPCR19) agonist or a pharmaceutically acceptable salt thereof is cerebral amyloid angiopathy, disorder associated with cognitive impairment, mild cognitive impairment, attention deficit symptom associated with Alzheimer's disease ,
- a disease selected from the group consisting of neurodegeneration associated with Alzheimer's disease, dementia, elderly dementia, senile dementia, cerebrovascular dementia, alcoholic dementia, dementia associated with Parkinson's disease, amyloid ⁇ -related conditions that are peek disorders and cortical basal ganglia degeneration It can be used for the purpose of preventing, improving or delaying.
- containing as an active ingredient means containing a dosage range that has the effect of preventing, treating or delaying Alzheimer's disease or dementia, the dosage range may vary depending on the severity and dosage form, and the frequency of application It may vary depending on the age, weight and constitution of the subject.
- treatment includes the cure of Alzheimer's disease or dementia as well as the partial cure, improvement and alleviation of Alzheimer's disease or dementia as a result of applying the pharmaceutical composition of the invention to an individual with Alzheimer's disease or dementia.
- prevention is to apply the pharmaceutical composition of the present invention to an individual with Alzheimer's disease or dementia to suppress or block symptoms or symptoms, such as cognitive impairment, behavioral disorders, brain nerve destruction, etc. It means not to generate.
- improved is meant to include alleviation, prevention or treatment of symptoms.
- active ingredient refers to a component that exhibits activity alone or in combination with a carrier (carrier) inactive itself.
- the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount
- the term "pharmaceutically effective amount” in the present invention is an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to medical treatment or improvement.
- Effective dose levels are well-known for individual types and severities, age, sex, drug activity, drug sensitivity, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other medical fields. It can be determined according to known factors.
- the term "individual” means any animal, including a human who has already developed or may have Alzheimer's disease or dementia, and the GPCR19 agonist or sodium taurodeoxycholate or derivative thereof according to the present invention.
- the disease can be effectively prevented and ameliorated.
- the present invention includes the step of administering a G protein-coupled receptor 19 (GPCR19) agonist or a pharmaceutically acceptable salt thereof to Alzheimer's disease (AD) or a subject suffering from dementia.
- GPCR19 G protein-coupled receptor 19
- AD Alzheimer's disease
- a subject suffering from dementia Provided are methods for preventing, delaying or treating Alzheimer's disease or dementia.
- the subject refers to all animals including humans having Alzheimer's disease or dementia, or humans, and may include humans, horses, sheep, pigs, goats, camels, and dogs, but are not limited thereto. It is not.
- the administration means introducing a predetermined substance into a subject including a human by a suitable method, and the route of administration of the G protein-coupled receptor 19 agent or a pharmaceutically acceptable salt thereof according to the present invention may reach the target tissue.
- Oral or parenteral eg, applied intravenously, subcutaneously, intraperitoneally, or topically
- any common route and may be administered by any device in which the active ingredient may migrate to target cells.
- the treatment is a result of applying the G protein-coupled receptor 19 agonist of the present invention or a pharmaceutically acceptable salt thereof to an individual having Alzheimer's disease or dementia, as well as partial cure of Alzheimer's disease or dementia, Improves and alleviates.
- the prophylaxis may be performed by applying the G protein-coupled receptor 19 agonist of the present invention or a pharmaceutically acceptable salt thereof to an individual having Alzheimer's disease or dementia, or a healthy individual.
- inhibiting or blocking it is meant that Alzheimer's disease or dementia symptoms do not occur in advance.
- Such improvement is meant to include alleviation, prevention or treatment of symptoms.
- the present invention also provides a G protein-Coupled Receptor 19 (GPCR19) agonist or a pharmaceutically acceptable agent thereof for use as a pharmaceutical composition for preventing, treating or delaying Alzheimer's disease (AD) or dementia.
- GPCR19 G protein-Coupled Receptor 19
- the use of the salt is provided.
- the present invention provides the use of a G protein-coupled receptor 19 (GPCR19) agonist or a pharmaceutically acceptable salt thereof for use as a food composition for preventing, improving or delaying Alzheimer's disease or dementia.
- GPCR19 G protein-coupled receptor 19
- the G protein-coupled receptor 19 agonist or pharmaceutically acceptable salt thereof according to the present invention when administered to a subject, does not harm the subject's health, exhibits an effect of improving cognitive and behavioral disorders, and prevents apoptosis of brain tissue.
- a pharmaceutical composition or plant composition that inhibits, enhances immunity, prevents Alzheimer's disease or dementia by reducing the formation of amyloid ⁇ (A ⁇ ) plaques, or delays or treats disease progression in individuals who have already developed the disease.
- a ⁇ amyloid ⁇
- the mouse On the first day of the experiment, the mouse was placed in a water tank at one side of the tank and allowed to swim for 3 minutes.After 3 minutes, the experimenter used the hand to move the mouse to the platform position and the mouse was placed on the platform. If left, it was left for 1 minute. After 1 minute, the mouse was lifted and wrapped with both hands, and then waited for 1 minute and then put back into the cage. This process was repeated three times in total. From the second day of the experiment, the prepared tank was immersed in water at one side of the tank (“position 1”) and the time until the mouse found the platform was recorded.
- the experimenter induced the mouse to move to the platform position by hand, left it for 30 seconds when the mouse climbed on the platform, held the mouse in two hands, and waited for 1 minute. After 1 minute, it was repeated at the other two positions in the tank (“Position 2”, “Position 3”) and finally at “Position 1”. This process was repeated every day until the differences between groups of mice narrowed.
- the platform was removed from the tank, the mouse was dropped into the tank, the video was recorded for 90 seconds, and the analysis software was used to analyze the movement path of the mouse, the number of passages of the platform, and the time on the platform.
- Control mice and Alzheimer's mice (four per group) were injected with 20 injections of PBS or sodium taurodioxycholate (1 mg / kg) twice a week, followed by a water maze experiment.
- the results of evaluating the spatial learning ability are shown in FIG. 2.
- Sodium taurodioxycholate drug administration confirmed that the time required for Alzheimer's mice to find a platform was shortened.
- mice and Alzheimer's mice (10 or more per group) were injected with PBS or sodium taurodioxycholate (1 mg / kg) twice a week for a total of 20 injections in a platform from which the platform was removed.
- Mouse behavior patterns were tracked. Representative images of mouse movement tracking results in the tank with the platform removed are shown in FIG. 3. In the group of sodium taurodioxycholate administered mice, the shift pattern to the position of the platform was more actively observed.
- the cerebrum, cerebellum, and soft water were separated and soaked in PFA for 20 hours, and then transferred to 30% sucrose for 3 days.
- Tissues were cut to 30 ⁇ m thickness using a microtome in the frozen state through OCT compounds.
- the cut tissue fragment was attached to the slide using a brush, blocked to prevent nonspecific antibody binding, and then reacted with an antibody (fluorescence bound) specific for the protein to be reported.
- the stained slide was taken after confirming the degree of fluorescence using a confocal microscope.
- the photographed images were converted into numerical values by measuring the intensity of fluorescence for each fluorescence using analytical software.
- mice and Alzheimer's mice (3 per group) were injected with 20 injections of PBS or sodium taurodioxycholate (1 mg / kg) twice a week, and then the frontal cortex in the brain of the mouse. Inflammatory amyloid ⁇ plaques and microglia and astrosite (inflammatory cells) in the hippocampus tissue were irradiated. The results are shown in FIGS. 5 and 6. The results showed that administration of sodium taurodioxycholate significantly reduced amyloid ⁇ plaque formation and microglia and astrosite cell distribution in the brain frontal cortex. It appeared to decrease.
- INOS which produces ROS that represents cytotoxicity in the prefrontal cortex of the mouse, after 20 injections of PBS or sodium taurodioxycholate (1 mg / kg) twice a week in Alzheimer's mice (3 per group)
- the result of fluorescein staining is shown in FIG.
- Administration of sodium taurodioxycholate has been shown to significantly reduce iNOS expression in the cerebral frontal cortex.
- Brain tissues of the Alzheimer's model mice administered with the drug were extracted and measured by fluorescence staining to reduce lesions such as apoptotic lesions in the frontal cortex and hippocampal region, and the results are shown in FIG. 8. same.
- PBS or sodium taurodioxycholate were administered to Alzheimer's mice, and the sites damaged by apoptosis were analyzed by TUNEL staining in the frontal cortex of the mice. As a result, the administration of sodium taurodioxycholate reduced the apoptotic region in brain tissue.
- Blood was obtained from a mouse by heart or orbital blood collection.
- the obtained blood was left at room temperature for 2 hours, centrifuged to obtain a supernatant, and then quantitative analysis of each inflammatory material was performed using kits and equipment for Bioplex.
- biochemical and blood cell analysis the obtained blood was placed in an appropriate tube or container and applied to a biochemical analyzer and a hemocytometer, respectively, to obtain data.
- the powders are mixed and mixed, followed by filling into an airtight fabric to prepare a powder.
- Tablets are prepared by mixing the above components according to a conventional method for preparing tablets and then compressing them.
- the capsules are prepared by mixing the above components and filling the gelatin capsules according to a conventional capsule preparation method.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Physiology (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
Claims (16)
- G단백질 결합형 수용체19(G protein-Coupled Receptor19, GPCR19) 작용제 또는 이의 약학적으로 허용되는 염을 유효성분으로 함유하는 알츠하이머 질환(Alzheimer Disease, AD) 또는 치매 예방, 치료 또는 지연용 약학적 조성물.
- 제1항에 있어서,상기 G단백질 결합형 수용체19(GPCR19) 작용제는 소듐 타우로디옥시콜레이트(Sodium taurodeoxycholate)인 것을 특징으로 하는 알츠하이머 질환 또는 치매 예방, 치료 또는 지연용 약학적 조성물.
- 제1항에 있어서,상기 약학적 조성물은 경구, 직장, 정맥내, 근육내, 복강내, 피하, 비내 및 경피 투여용 제제의 형태로 제형화 되는 것을 특징으로 하는 알츠하이머 질환 또는 치매 예방, 치료 또는 지연용 조성물.
- 제1항에 있어서,G단백질 결합형 수용체19(GPCR19) 작용제 또는 이의 약학적으로 허용되는 염은, 대뇌 아밀로이드 혈관병증, 인지 손상과 관련된 장애, 경증인지손상, 알츠하이머 질환과 관련된 주의력 결핍 증상, 알츠하이머 질환과 관련된 신경퇴행, 퇴행성 치매, 초로성 치매, 노인성 치매, 뇌혈관성 치매, 알코올성 치매, 파킨슨 질환과 관련된 치매, 픽장애 및 피질 기저핵 변성인 아밀로이드β-관련 병증으로 구성된 그룹으로부터 선택되는 질환을 예방, 치료 또는 지연시키기 위한 것을 특징으로 하는, 알츠하이머 질환 또는 치매 예방, 치료 또는 지연용 약학적 조성물.
- 제1항에 있어서,G단백질 결합형 수용체19(GPCR19) 작용제 또는 이의 약학적으로 허용되는 염이 0.1 mg/kg/일 내지 1000 mg/kg/일의 양으로 투여되도록 제제화된 알츠하이머 질환 또는 치매 예방, 치료 또는 지연용 약학적 조성물.
- 제1항에 있어서,G단백질 결합형 수용체19(GPCR19) 작용제 또는 이의 약학적으로 허용되는 염이 1 mg/kg/일 내지 500 mg/kg/일의 양으로 투여되도록 제제화된 알츠하이머 질환 또는 치매 예방, 치료 또는 지연용 약학적 조성물.
- 제1항에 있어서,G단백질 결합형 수용체19(GPCR19) 작용제 또는 이의 약학적으로 허용되는 염이 10 mg/kg/일 내지 100 mg/kg/일의 양으로 투여되도록 제제화된 알츠하이머 질환 또는 치매 예방, 치료 또는 지연용 약학적 조성물.
- 제1항에 있어서,G단백질 결합형 수용체19(GPCR19) 작용제 또는 이의 약학적으로 허용되는 염이 1주일에 1회 내지 3회 투여되는 것을 특징으로 하는, 알츠하이머 질환 또는 치매 예방, 치료 또는 지연용 약학적 조성물.
- 제1항에 있어서,G단백질 결합형 수용체19(GPCR19) 작용제 또는 이의 약학적으로 허용되는 염과, 인지 강화제, 기억강화제 및 콜린 에스테라아제 억제제로 구성된 그룹으로부터 선택되는 1종 이상의 약물이 배합된 것을 특징으로 하는, 알츠하이머 질환 또는 치매 예방, 치료 또는 지연용 약학적 조성물.
- G단백질 결합형 수용체19(G protein-Coupled Receptor19, GPCR19) 작용제 또는 이의 약학적으로 허용되는 염을 함유하는 알츠하이머 질환(Alzheimer Disease, AD) 또는 치매를 예방, 개선 또는 지연용 식품 조성물.
- 제10항에 있어서,상기 G단백질 결합형 수용체19(GPCR19) 작용제는 소듐 타우로디옥시콜레이트(Sodium taurodeoxycholate)인 것을 특징으로 하는 알츠하이머 질환 또는 치매 예방, 개선 또는 지연용 식품 조성물.
- 제10항에 있어서,상기 G단백질 결합형 수용체19(GPCR19) 작용제 또는 이의 약학적으로 허용되는 염은, 대뇌 아밀로이드 혈관병증, 인지 손상과 관련된 장애, 경증인지손상, 알츠하이머 질환과 관련된 주의력 결핍 증상, 알츠하이머 질환과 관련된 신경퇴행, 퇴행성 치매, 초로성 치매, 노인성 치매, 뇌혈관성 치매, 알코올성 치매, 파킨슨 질환과 관련된 치매, 픽장애 및 피질 기저핵 변성인 아밀로이드β-관련 병증으로 구성된 그룹으로부터 선택되는 질환을 예방, 개선 또는 지연시키기 위한 것을 특징으로 하는, 알츠하이머 질환 또는 치매 예방, 개선 또는 지연용 식품 조성물.
- G단백질 결합형 수용체19(G protein-Coupled Receptor19, GPCR19) 작용제 또는 이의 약학적으로 허용되는 염을 알츠하이머 질환(Alzheimer Disease, AD) 또는 치매에 걸린 개체에 투여하는 단계를 포함하는 알츠하이머 질환 또는 치매 지연 또는 치료방법.
- G단백질 결합형 수용체19(G protein-Coupled Receptor19, GPCR19) 작용제 또는 이의 약학적으로 허용되는 염을 개체에 투여하는 단계를 포함하는 알츠하이머 질환 또는 치매 예방 방법.
- 알츠하이머 질환(Alzheimer Disease, AD) 또는 치매 예방, 치료 또는 지연용 약학적 조성물로 사용하기 위한 G단백질 결합형 수용체19(G protein-Coupled Receptor19, GPCR19) 작용제 또는 이의 약학적으로 허용되는 염의 용도.
- 알츠하이머 질환 또는 치매 예방, 개선 또는 지연용 식품 조성물로 사용하기 위한 G단백질 결합형 수용체19(G protein-Coupled Receptor19, GPCR19) 작용제 또는 이의 약학적으로 허용되는 염의 용도.
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES16821505T ES2750839T3 (es) | 2015-07-06 | 2016-01-15 | Composición farmacéutica para la prevención, tratamiento o retraso de la enfermedad de Alzheimer o demencia que contiene agente receptor acoplado a proteína G 19 como ingrediente activo |
US15/516,317 US10071107B2 (en) | 2015-07-06 | 2016-01-15 | Pharmaceutical composition for prevention, treatment or delay of Alzheimer's disease or dementia containing G protein-coupled receptor 19 agent as active ingredient |
CN201680002150.3A CN106794189A (zh) | 2015-07-06 | 2016-01-15 | 阿尔茨海默疾病或痴呆预防、治疗或拖延用药学组合物 |
JP2017505858A JP6426273B2 (ja) | 2015-07-06 | 2016-01-15 | Gpcr19作用剤を有効成分として含有する、アルツハイマー病または認知症を予防、治療、または遅延させるための薬学的組成物 |
EP16821505.1A EP3248603B1 (en) | 2015-07-06 | 2016-01-15 | Pharmaceutical composition for prevention, treatment or delay of alzheimer's disease or dementia containing g protein-coupled receptor 19 agent as active ingredient |
US16/123,703 US10342807B2 (en) | 2015-07-06 | 2018-09-06 | Pharmaceutical composition for prevention, treatment or delay of Alzheimer's disease or dementia containing G protein-coupled receptor 19 agent as active ingredient |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020150095951A KR101743960B1 (ko) | 2015-07-06 | 2015-07-06 | G단백질 결합형 수용체19 작용제를 유효성분으로 함유하는 알츠하이머 질환 또는 치매를 예방, 치료 또는 지연하기 위한 약학적 조성물 |
KR10-2015-0095951 | 2015-07-06 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/516,317 A-371-Of-International US10071107B2 (en) | 2015-07-06 | 2016-01-15 | Pharmaceutical composition for prevention, treatment or delay of Alzheimer's disease or dementia containing G protein-coupled receptor 19 agent as active ingredient |
US16/123,703 Continuation US10342807B2 (en) | 2015-07-06 | 2018-09-06 | Pharmaceutical composition for prevention, treatment or delay of Alzheimer's disease or dementia containing G protein-coupled receptor 19 agent as active ingredient |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2017007099A1 true WO2017007099A1 (ko) | 2017-01-12 |
Family
ID=57685439
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2016/000447 WO2017007099A1 (ko) | 2015-07-06 | 2016-01-15 | G단백질 결합형 수용체19 작용제를 유효성분으로 함유하는 알츠하이머 질환 또는 치매를 예방, 치료 또는 지연하기 위한 약학적 조성물 |
Country Status (7)
Country | Link |
---|---|
US (2) | US10071107B2 (ko) |
EP (1) | EP3248603B1 (ko) |
JP (1) | JP6426273B2 (ko) |
KR (1) | KR101743960B1 (ko) |
CN (2) | CN106794189A (ko) |
ES (1) | ES2750839T3 (ko) |
WO (1) | WO2017007099A1 (ko) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3694523A4 (en) * | 2017-10-13 | 2021-07-07 | Locus IP Company, LLC | METHODS AND SUBSTANCES FOR PREVENTION AND TREATMENT OF NEURODEGENERATIVE DISEASES |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102010655B1 (ko) | 2017-09-15 | 2019-08-13 | 재단법인대구경북과학기술원 | 알츠하이머병 진단을 위한 신규한 단백질 마커 및 이의 용도 |
US20230348978A1 (en) * | 2020-01-07 | 2023-11-02 | Selonterra, Inc. | Treatment of alzheimer's disease |
WO2022059948A1 (ko) | 2020-09-18 | 2022-03-24 | 서울대학교 산학협력단 | 소디움 타우로디옥시콜레이트의 대량 생산 방법 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004083867A2 (en) * | 2003-03-17 | 2004-09-30 | Arena Pharmaceuticals Inc. | Modulators of g protein-coupled formyl peptide receptor-like 2 and their therapeutic use against cell death-related disorders |
KR100785656B1 (ko) | 2007-05-14 | 2007-12-17 | 재단법인서울대학교산학협력재단 | 소염제로 사용되는 소디움글리코콜레이트 또는 그 유도체 |
US20080312332A1 (en) * | 2005-12-26 | 2008-12-18 | Shanghai Institues For Biological Sciences, Chinese Academy Of Sciences | G Protein-Coupled Receptor Antagonist and Its Use for Preventing and Treating Alzheimer's Disease |
KR20130103468A (ko) * | 2013-08-26 | 2013-09-23 | 서울대학교산학협력단 | Gpcr19 경로의 활성화에 의한 골수 유래 면역 조절 세포 및 면역 조절 b 림프구의 체내외 증폭 |
KR101452864B1 (ko) | 2011-11-17 | 2014-11-04 | 서울대학교산학협력단 | Gpcr19 경로의 활성화에 의한 골수 유래 면역 조절 세포 및 면역 조절 b 림프구의 체내외 증폭 |
KR101494275B1 (ko) | 2013-08-26 | 2015-02-24 | 서울대학교기술지주 주식회사 | Gpcr19 경로의 활성화에 의한 골수 유래 면역 조절 세포 및 면역 조절 b 림프구의 체내외 증폭 |
KR20150029043A (ko) | 2013-08-26 | 2015-03-18 | 서울대학교기술지주 주식회사 | Gpcr19 작용제를 유효성분으로 함유하는 아토피 예방 또는 치료용 조성물 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9503601D0 (en) * | 1995-02-23 | 1995-04-12 | Merck Sharp & Dohme | Method of treatment and method of manufacture of medicament |
GB9805561D0 (en) * | 1998-03-16 | 1998-05-13 | Merck Sharp & Dohme | A combination of therapeutic agents |
US6531478B2 (en) * | 2000-02-24 | 2003-03-11 | Cheryl P. Kordik | Amino pyrazole derivatives useful for the treatment of obesity and other disorders |
JP2004346059A (ja) * | 2003-01-28 | 2004-12-09 | Takeda Chem Ind Ltd | 受容体作動薬 |
KR101358078B1 (ko) | 2004-11-01 | 2014-02-06 | 주식회사 유스팜인터내셔널 | 근위축성 측삭 경화증의 신경퇴행을 감소시키기 위한 방법및 조성물 |
US20080031968A1 (en) * | 2005-04-01 | 2008-02-07 | The Brigham And Women's Hospital, Inc. | Methods for increasing cellular energy expenditure |
US20090246170A1 (en) * | 2006-05-31 | 2009-10-01 | Dnavec Corporation | Therapeutic Agent For Alzheimer's Disease |
CN101679304A (zh) * | 2007-04-13 | 2010-03-24 | 诺瓦提斯公司 | 作为gpbar1激动剂的哒嗪-、吡啶-和吡喃-衍生物 |
AU2010225923B2 (en) * | 2009-03-16 | 2016-10-27 | Ipintl, Llc | Treating Alzheimer's disease and osteoporosis and reducing aging |
NZ598906A (en) * | 2009-08-21 | 2014-08-29 | Targeted Delivery Technologies Ltd | Vesicular formulations |
BR112015003395A2 (pt) | 2012-08-16 | 2017-07-04 | Janssen Pharmaceutica Nv | pirazóis substituídos como bloqueadores de canal de cálcio de tipo-n |
US9872865B2 (en) * | 2013-03-24 | 2018-01-23 | Amylyx Pharmaceuticals Inc. | Compositions for improving cell viability and methods of use thereof |
-
2015
- 2015-07-06 KR KR1020150095951A patent/KR101743960B1/ko active IP Right Grant
-
2016
- 2016-01-15 WO PCT/KR2016/000447 patent/WO2017007099A1/ko active Application Filing
- 2016-01-15 ES ES16821505T patent/ES2750839T3/es active Active
- 2016-01-15 CN CN201680002150.3A patent/CN106794189A/zh active Pending
- 2016-01-15 EP EP16821505.1A patent/EP3248603B1/en active Active
- 2016-01-15 US US15/516,317 patent/US10071107B2/en active Active
- 2016-01-15 CN CN202111363187.8A patent/CN114028406A/zh active Pending
- 2016-01-15 JP JP2017505858A patent/JP6426273B2/ja active Active
-
2018
- 2018-09-06 US US16/123,703 patent/US10342807B2/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004083867A2 (en) * | 2003-03-17 | 2004-09-30 | Arena Pharmaceuticals Inc. | Modulators of g protein-coupled formyl peptide receptor-like 2 and their therapeutic use against cell death-related disorders |
US20080312332A1 (en) * | 2005-12-26 | 2008-12-18 | Shanghai Institues For Biological Sciences, Chinese Academy Of Sciences | G Protein-Coupled Receptor Antagonist and Its Use for Preventing and Treating Alzheimer's Disease |
KR100785656B1 (ko) | 2007-05-14 | 2007-12-17 | 재단법인서울대학교산학협력재단 | 소염제로 사용되는 소디움글리코콜레이트 또는 그 유도체 |
KR101452864B1 (ko) | 2011-11-17 | 2014-11-04 | 서울대학교산학협력단 | Gpcr19 경로의 활성화에 의한 골수 유래 면역 조절 세포 및 면역 조절 b 림프구의 체내외 증폭 |
KR20130103468A (ko) * | 2013-08-26 | 2013-09-23 | 서울대학교산학협력단 | Gpcr19 경로의 활성화에 의한 골수 유래 면역 조절 세포 및 면역 조절 b 림프구의 체내외 증폭 |
KR101494275B1 (ko) | 2013-08-26 | 2015-02-24 | 서울대학교기술지주 주식회사 | Gpcr19 경로의 활성화에 의한 골수 유래 면역 조절 세포 및 면역 조절 b 림프구의 체내외 증폭 |
KR20150029043A (ko) | 2013-08-26 | 2015-03-18 | 서울대학교기술지주 주식회사 | Gpcr19 작용제를 유효성분으로 함유하는 아토피 예방 또는 치료용 조성물 |
Non-Patent Citations (6)
Title |
---|
CRAVEN, R., NAT REV. NEUROSCI., vol. 2, 2001, pages 533 |
DAVID, H. S. ET AL., NAT REV. NEUROSCI., vol. 2, 2001, pages 595 - 598 |
HARDY, J. ET AL., NAT NEUROSCI, vol. 1, 1998, pages 355 - 358 |
NATURE, vol. 399, 1999, pages A23 - A31 |
THATHIAH, A. ET AL.: "The Role of G Protein-coupled Receptors in the Pathology of Alzheimer's Disease", NATURE REVIEWS NEUROSCIENCE, vol. 12, 2011, pages 73 - 87, XP055346081 * |
YANKNER, B. A., NEURON, vol. 16, 1996, pages 921 - 932 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3694523A4 (en) * | 2017-10-13 | 2021-07-07 | Locus IP Company, LLC | METHODS AND SUBSTANCES FOR PREVENTION AND TREATMENT OF NEURODEGENERATIVE DISEASES |
US11478494B2 (en) | 2017-10-13 | 2022-10-25 | Locus Ip Company, Llc | Methods and substances for prevention and treatment of neurodegenerative diseases |
Also Published As
Publication number | Publication date |
---|---|
CN114028406A (zh) | 2022-02-11 |
US10342807B2 (en) | 2019-07-09 |
JP2017523982A (ja) | 2017-08-24 |
US20180104261A1 (en) | 2018-04-19 |
KR20170005940A (ko) | 2017-01-17 |
EP3248603A1 (en) | 2017-11-29 |
US20190000863A1 (en) | 2019-01-03 |
KR101743960B1 (ko) | 2017-06-08 |
ES2750839T3 (es) | 2020-03-27 |
EP3248603B1 (en) | 2019-07-17 |
EP3248603A4 (en) | 2017-12-27 |
CN106794189A (zh) | 2017-05-31 |
US10071107B2 (en) | 2018-09-11 |
JP6426273B2 (ja) | 2018-11-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Bönöczk et al. | Role of sodium channel inhibition in neuroprotection: effect of vinpocetine | |
WO2017007099A1 (ko) | G단백질 결합형 수용체19 작용제를 유효성분으로 함유하는 알츠하이머 질환 또는 치매를 예방, 치료 또는 지연하기 위한 약학적 조성물 | |
WO2010058926A2 (ko) | 생강 추출물 또는 쇼가올을 포함하는 약학 조성물 | |
US20160310481A1 (en) | Laquinimod for treatment of cannabinoid receptor type 1(cb1) mediated disorders | |
CN113292524B (zh) | 丁苯酞衍生物及其在制备保护神经细胞的药物中的应用 | |
US20220401414A1 (en) | Treatment and prevention of a neurodegenerative disorder | |
KR102630042B1 (ko) | 알츠하이머병의 치료를 위한 항-a베타 원시섬유 항체 및 베타-세크레타제 bace1 억제제를 포함하는 조성물 | |
WO2010036052A2 (ko) | 4-o-메틸호노키올을 함유하는 아밀로이드 관련 질환의 치료 또는 예방용 조성물 | |
WO2022055285A1 (ko) | 암의 기원 세포의 사멸용 약학적 조성물 | |
WO2017094956A1 (ko) | 방사선 보호용 또는 완화용 약학 조성물 | |
US20140045886A1 (en) | Laquinimod for treatment of gaba mediated disorders | |
WO2020262971A1 (ko) | 미토콘드리아 기능이상으로 인한 질환의 예방 또는 치료용 조성물 | |
JP2906339B2 (ja) | 活性成分としてデヒドロエボジアミン−HClを含有する記憶増強および抗痴呆剤 | |
WO2022114906A1 (ko) | 신규 퇴행성 신경질환 치료용 약학적 조성물 | |
JP6797840B2 (ja) | フペルジンを含有する組合せ組成物 | |
WO2022181920A1 (ko) | 엘레우테로사이드 b를 유효성분으로 포함하는 뇌신경염증 치료용 약학적 조성물 | |
WO2022158639A1 (ko) | 베타아밀로이드 및 타우 단백질 집적과 연관된 질환 치료용 약학적 조성물 | |
CN113301893A (zh) | 神经性疾病的治疗 | |
WO2011132831A1 (ko) | 글루타민의 우울증 예방, 치료 또는 진단을 위한 용도 | |
WO2024058552A1 (ko) | 칸나비노이드를 유효성분으로 포함하는 퇴행성 뇌질환 예방 또는 치료용 약학 조성물 및 이의 용도 | |
WO2023229445A1 (ko) | 신규 펩타이드 및 그의 용도 | |
WO2023229443A1 (ko) | 신규 펩타이드 및 그의 용도 | |
WO2013039271A1 (ko) | 뇌손상에 의한 전두엽 기능장애 모델 동물 및 전두엽 기능장애의 개선용 조성물 | |
WO2019216589A1 (ko) | 타우 관련 질환의 예방 또는 치료용 조성물 | |
WO2018155956A1 (ko) | 백합 비늘줄기 추출물을 포함하는 인지장애의 예방 또는 치료용 약학 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
REEP | Request for entry into the european phase |
Ref document number: 2016821505 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2016821505 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2017505858 Country of ref document: JP Kind code of ref document: A |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 16821505 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 15516317 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |