CN116270582A - Use of fenofibrate - Google Patents
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- CN116270582A CN116270582A CN202211478021.5A CN202211478021A CN116270582A CN 116270582 A CN116270582 A CN 116270582A CN 202211478021 A CN202211478021 A CN 202211478021A CN 116270582 A CN116270582 A CN 116270582A
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- fenofibrate
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- alzheimer
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- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 229960002297 fenofibrate Drugs 0.000 title claims abstract description 40
- 239000003814 drug Substances 0.000 claims abstract description 33
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 11
- 208000024827 Alzheimer disease Diseases 0.000 claims description 38
- 238000002360 preparation method Methods 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 210000000653 nervous system Anatomy 0.000 claims description 10
- 230000003412 degenerative effect Effects 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000000443 aerosol Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000001179 sorption measurement Methods 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 5
- 210000005013 brain tissue Anatomy 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 108010010234 HDL Lipoproteins Proteins 0.000 description 4
- 102000015779 HDL Lipoproteins Human genes 0.000 description 4
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 238000012347 Morris Water Maze Methods 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- MQOBSOSZFYZQOK-UHFFFAOYSA-N fenofibric acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 MQOBSOSZFYZQOK-UHFFFAOYSA-N 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000010998 test method Methods 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- 238000012795 verification Methods 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 229960001231 choline Drugs 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000007087 memory ability Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- MZTKIKBXDMDCDY-UHFFFAOYSA-N 2-[4-(4-hydroxybenzoyl)phenoxy]-2-methylpropanoic acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C(=O)C1=CC=C(O)C=C1 MZTKIKBXDMDCDY-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 229910020366 ClO 4 Inorganic materials 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 206010070246 Executive dysfunction Diseases 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 201000007201 aphasia Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229960003653 choline fenofibrate Drugs 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 229960000701 fenofibric acid Drugs 0.000 description 2
- 229940125753 fibrate Drugs 0.000 description 2
- 230000002431 foraging effect Effects 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000003825 glutamate receptor antagonist Substances 0.000 description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 230000009965 odorless effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229960004526 piracetam Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 230000009967 tasteless effect Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 102100033639 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 241000629412 Ligustrum robustum Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000007131 anti Alzheimer effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000009189 diving Effects 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical class NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005065 mining Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 201000009570 retrograde amnesia Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229940126673 western medicines Drugs 0.000 description 1
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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- 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
-
- 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
Abstract
The invention relates to the technical field of biological medicines, in particular to application of fenofibrate, which comprises application of fenofibrate or a derivative thereof in preparing medicines for preventing and/or treating nervous system degenerative diseases.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of fenofibrate, in particular to application of fenofibrate in preparation of medicines for treating neurodegenerative diseases including Alzheimer's disease.
Background
Alzheimer's Disease (AD) is a degenerative disorder of the nervous system, and due to its complex pathological mechanism, the onset of the disease is hidden, usually with a course of up to 10-25 years. The main clinical manifestation of AD is progressive cognitive dysfunction, and is gradually aggravated until the AD is free of autonomy, the whole process has no obvious typical symptoms, so the AD is very easy to ignore, and along with the longer course of the AD, most patients have no regeneration opportunity of apoptotic nerves in the brain at the time of diagnosis, which makes the treatment of AD difficult. Therefore, the development of a drug with good curative effect and high safety is very important for the treatment of the disease.
Western medicines currently used for treating AD mainly comprise acetylcholinesterase inhibitors, glutamate receptor antagonists, piracetam and other medicines for relieving AD symptoms. The acetylcholinesterase inhibitor can inhibit AChE production, increase Ach content, thereby increasing choline activity in human body, improving learning and memory ability, and improving AD symptoms, such as tacrine, donepezil, galantamine, rismin, etc. Glutamate receptor antagonists can inhibit the hyperactive state of Glu in the central nervous system, thereby reducing neuronal damage. Piracetam is a brain metabolism improving drug, belongs to a ring-shaped derivative of Y-aminobutyric acid, and can promote acetylcholine synthesis, strengthen nerve excitation and conduction and promote brain metabolism; meanwhile, the Chinese medicinal composition can also resist brain injury caused by chemical, physical and other factors, improve retrograde amnesia symptoms caused by hypoxia, and has obvious promotion effects on enhancing memory and improving learning ability. In addition, the traditional Chinese medicine has the advantages of good treatment effect, small side effect and the like, and the research of the traditional Chinese medicine in recent years is in an increasing situation. For example, patent CN201610601343.2 discloses a preparation method of kudingcha extract and its application in the treatment of neurodegenerative diseases such as alzheimer's disease. Patent cn201810979961.X discloses the use of a brain-benefiting tablet in anti-alzheimer's disease, wherein the administration of an aqueous brain-benefiting tablet solution to mice is performed, and the brain-benefiting tablet has the effects of preventing and treating the alzheimer's disease through behavioral experiments (mining experiments, diving platform experiments, Y maze experiments and water maze experiments), immunohistochemistry, serum and cerebral cortex ELISA assays and western blot, can reduce the formation of aβ plaques in the brain, and can improve the pathological conditions of the alzheimer's disease through adjusting oxidative stress and cholinergic systems.
Fenofibrate (fenofibrate) with formula C 20 H 21 ClO 4 Is white or quasi-white crystalline powder, odorless and tasteless. Is very soluble in chloroform, is very soluble in acetone or diethyl ether, is slightly soluble in ethanol, and is almost insoluble in water. Fenofibrate is used primarily to lower cholesterol levels in patients at risk of cardiovascular disease, as other fibrates, reduces Low Density Lipoprotein (LDL) and Very Low Density Lipoprotein (VLDL) levels, and can raise High Density Lipoprotein (HDL) levels and lower Triglyceride (TG) levels. Fenofibrate can be used alone or in combination with statin to treat hypercholesterolemia and hypertriglyceridemia.
At present, fenofibrate has not been studied for the treatment of Alzheimer's disease.
Disclosure of Invention
In view of the above-mentioned shortcomings, the applicant has unexpectedly found that fenofibrate has a very good therapeutic effect on neurodegenerative disorders, in particular for alzheimer's disease, in a clinical real world study of fenofibrate; the applicant has verified through animal experiments.
The application provides application of fenofibrate in preparing a medicine for treating Alzheimer disease. According to the invention, the fenofibrate can reduce the content of beta-AP in brain tissues and improve memory disorder, so that the fenofibrate can be used for treating nervous system degenerative disorders such as Alzheimer's disease and the like, and a new thought is provided for treating the nervous system degenerative disorders such as Alzheimer's disease and the like.
In order to achieve the above object, the present invention has the following technical scheme:
in one aspect, the present invention provides the use of fenofibrate or a derivative thereof in the manufacture of a medicament for the prevention and/or treatment of a degenerative disorder of the nervous system.
Specifically, the neurodegenerative disorder is Alzheimer's disease.
In yet another aspect, the invention provides a medicament for treating a neurodegenerative disorder, the medicament comprising fenofibrate or a fenofibrate derivative.
The fenofibrate derivatives of the present invention include, but are not limited to: fenofibric acid, choline fenofibrate, and the like.
Specifically, the neurodegenerative disorder is Alzheimer's disease.
Specifically, the medicament also comprises a pharmaceutically acceptable carrier.
The carrier includes, but is not limited to, any one or more of a slow release agent, an excipient, a filler, a binder, a wetting agent, a disintegrant, an absorption enhancer, an adsorption carrier, a surfactant, or a lubricant.
Specifically, the medicine is any one of an external preparation, an oral preparation or an injection preparation.
Further specifically, the external preparation is a spray or an aerosol.
More specifically, the oral preparation is any one of granules, capsules, tablets or vesicles.
Further specifically, the injection preparation adopts intradermal, subcutaneous, intramuscular, local or intravenous injection as a mode of administration.
The fenofibrate is as follows: fenofibrate (fenofibrate) with formula C 20 H 21 ClO 4 Is white or quasi-white crystalline powder, odorless and tasteless. Is very soluble in chloroform, is very soluble in acetone or diethyl ether, is slightly soluble in ethanol, and is almost insoluble in water. Fenofibrate is used primarily to lower cholesterol levels in patients at risk of cardiovascular disease. As with other fibrates, fenofibrate reduces Low Density Lipoprotein (LDL) and Very Low Density Lipoprotein (VLDL) levels, and can raise High Density Lipoprotein (HDL) levels and lower Triglyceride (TG) levels. Fenofibrate can be used alone or in combination with statin to treat hypercholesterolemia and hypertriglyceridemia.
Compared with the prior art, the invention has the following positive and beneficial effects:
the fenofibrate or the derivative thereof can reduce the content of beta-AP in brain tissues and improve memory disorder, so that the fenofibrate or the derivative thereof can be used for treating nervous system degenerative disorders such as Alzheimer's disease and the like, and a new thought is provided for treating the nervous system degenerative disorders such as Alzheimer's disease and the like.
Alzheimer's Disease (AD) as described herein is a progressive degenerative disease of the nervous system with hidden onset. Clinically, global dementia characterized by memory impairment, aphasia, disuse, disrecognition, impairment of visual space skills, executive dysfunction, personality and behavioral changes, etc., has heretofore been unknown in etiology. The patient before 65 years old is called Alzheimer's disease; senile dementia is a disease occurring after 65 years of age.
The application adopts a classical pharmacodynamic method to verify the therapeutic effect of fenofibrate or derivatives thereof on Alzheimer's disease.
The fenofibrate or fenofibrate acid choline can be used as a pharmaceutical preparation which is already marketed currently or a new pharmaceutical preparation which is used in clinical application according to the specification.
The fenofibrate has good therapeutic effect on patients with Alzheimer's disease in the treatment process of patients with hyperlipidemia in real world research; the clinical test is to carry out systematic and scientific research; it is required to pass the verification of preclinical animal experiments and the clinical trial research of the system, so that the medicine can be used as a new indication.
The application is a conclusive use obtained by the applicant after years of clinical verification.
Detailed Description
The present invention will be described in further detail with reference to the following examples, which are not intended to limit the present invention, but are merely illustrative of the present invention. The experimental methods used in the following examples are not specifically described, but the experimental methods in which specific conditions are not specified in the examples are generally carried out under conventional conditions, and the materials, reagents, etc. used in the following examples are commercially available unless otherwise specified.
Where numerical ranges are provided in the examples, it is understood that unless otherwise stated herein, both endpoints of each numerical range and any number between the two endpoints are significant both in the numerical range. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It should be noted that the raw materials used in the present invention are all common commercial products, and therefore the sources thereof are not particularly limited.
Example 1
The test method comprises the following steps:
balb/c mice, male, weighing 18-22g. (supplied by the university of Shenyang pharmacy department pharmacology)
Mice were taken and randomly divided into 3 groups: the blank control group, the model group and the test drug group are subjected to gastric administration, wherein the dosage of the aluminum trichloride is 20mg/kg, 1 time a day, 90 days continuously, and D-galactose is adopted for subcutaneous injection at 38 days, 150mg/kg, 1 time a 3 days and 90 days. On day 61, drug intervention was started, test drug group: fenofibrate was administered by gavage at a dose of 0.5g/kg 1 time per day for 30 consecutive days, and the model group and the blank group were given an equivalent amount of physiological saline by gavage for 30 consecutive days. The test method refers to the literature method.
(1) Morris Water Maze (MWM) experiment
The effect of fenofibrate on the learning and memory ability of mice was examined 3 hours after the last dose using Morris Water Maze (MWM) test, and the results are shown in Table 1 below.
TABLE 1 influence on learning and memory in mice
Note that: p <0.01, P <0.05 compared to model group.
(2) beta-AP detection
After the mice were sacrificed under anesthesia, the brains of the mice were taken and the content of β -AP in the brain tissues of the mice was detected.
The detection results are shown in the following table 2.
TABLE 2 content of beta-AP in brain tissue of mice
| Group of | Animal number (only) | β-AP(pg/mL) |
| Blank pairPhoto group | 10 | 41.79±3.85** |
| Model group | 10 | 72.49±5.92 |
| Experimental group | 10 | 52.28±3.76** |
Note that: p <0.01, P <0.05 compared to model group.
Conclusion of the test: from the above tables 1 and 2, the fenofibrate provided by the invention can effectively inhibit the increase of beta-AP in the brain tissue of the mouse, and improve the learning and memory ability of the mouse; fully shows that the fenofibrate has good preventing and relieving effects on Alzheimer's disease.
Example 2
The test method comprises the following steps:
balb/c mice, male, weighing 18-22g. (supplied by the university of Shenyang pharmacy department pharmacology department),
mice were randomly grouped into 3 groups: blank, model, test, 10 per group. Wherein, the model group is administrated with normal saline in a lavage way for 11 days continuously, the test group is administrated with fenofibrate in a lavage way for 0.5g/kg, 1 time a day continuously for 11 days. Starting on day 5 of dosing, mice were maze trained daily at 9:00 a.m. to 11:30 a.m., fasted 17:00 a.m. to 9:00 a.m. the next day, for 6 consecutive days. After the last training, mice in the model group and the test group respectively inject NaNO subcutaneously 2 120mg/kg, a blank group was intraperitoneally injected with an equal amount of physiological saline, and after 24 hours mice were tested for foraging time (time from maze starting point to feeding chamber). The test method refers to the literature method.
The detection results are shown in table 3 below.
TABLE 3 influence on the foraging time of mice
Note that: p <0.01, P <0.05 compared to model group.
Conclusion of the test: as can be seen from Table 3, the fenofibrate of the present invention is effective in improving NaNO 2 Resulting in dysmnesia in mice.
The fenofibrate derivatives of the present invention include, but are not limited to: fenofibric acid, choline fenofibrate, and the like.
Specifically, the medicament also comprises a pharmaceutically acceptable carrier.
The carrier is one or more of slow release agent, excipient, filler, adhesive, wetting agent, disintegrating agent, absorption promoter, adsorption carrier, surfactant or lubricant.
Specifically, the medicine is any one of an external preparation, an oral preparation or an injection preparation.
Further specifically, the external preparation is a spray or an aerosol.
More specifically, the oral preparation is any one of granules, capsules, tablets or vesicles.
Further specifically, the injection preparation adopts intradermal, subcutaneous, intramuscular, local or intravenous injection as a mode of administration.
Alzheimer's Disease (AD) as described herein is a progressive degenerative disease of the nervous system with hidden onset. Clinically, global dementia characterized by memory impairment, aphasia, disuse, disrecognition, impairment of visual space skills, executive dysfunction, personality and behavioral changes, etc., has heretofore been unknown in etiology. The patient before 65 years old is called Alzheimer's disease; senile dementia is a disease occurring after 65 years of age.
The application adopts a classical pharmacodynamic method to verify the therapeutic effect of fenofibrate or derivatives thereof on Alzheimer's disease.
The fenofibrate or fenofibrate acid choline can be used as a pharmaceutical preparation which is already marketed currently or a new pharmaceutical preparation which is used in clinical application according to the specification.
The fenofibrate has good therapeutic effect on patients with Alzheimer's disease in the treatment process of patients with hyperlipidemia in real world research; the clinical test is to carry out systematic and scientific research; it is required to pass the verification of preclinical animal experiments and the clinical trial research of the system, so that the medicine can be used as a new indication.
The application is a conclusive use obtained by the applicant after years of clinical verification.
The foregoing examples illustrate only a few embodiments of the invention and are described in detail herein without thereby limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (9)
1. Use of fenofibrate or a derivative thereof for the preparation of a medicament for the prevention and/or treatment of a degenerative disorder of the nervous system.
2. The use according to claim 1, characterized in that: the neurodegenerative disorder is Alzheimer's disease.
3. A medicament for treating a degenerative disorder of the nervous system, characterized in that: the medicine comprises fenofibrate or fenofibrate derivatives.
4. A medicament according to claim 3, characterized in that: the medicine also comprises a pharmaceutically acceptable carrier, wherein the carrier is any one or more of a slow release agent, an excipient, a filler, an adhesive, a wetting agent, a disintegrating agent, an absorption promoter, an adsorption carrier, a surfactant or a lubricant.
5. A medicament according to claim 3, characterized in that: the medicine is any one of an external preparation, an oral preparation or an injection preparation.
6. A medicament according to claim 5, characterized in that: the external preparation is spray or aerosol.
7. A medicament according to claim 5, characterized in that: the oral preparation is any one of granules, capsules, tablets or vesicles.
8. A medicament according to claim 5, characterized in that: the injection preparation adopts intradermal, subcutaneous, intramuscular, local or intravenous injection as an administration mode.
9. A medicament according to claim 3, characterized in that: the neurodegenerative disorder is Alzheimer's disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211478021.5A CN116270582A (en) | 2022-11-23 | 2022-11-23 | Use of fenofibrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211478021.5A CN116270582A (en) | 2022-11-23 | 2022-11-23 | Use of fenofibrate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116270582A true CN116270582A (en) | 2023-06-23 |
Family
ID=86802017
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211478021.5A Pending CN116270582A (en) | 2022-11-23 | 2022-11-23 | Use of fenofibrate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116270582A (en) |
-
2022
- 2022-11-23 CN CN202211478021.5A patent/CN116270582A/en active Pending
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