Application of amide compound in preparation of medicine for treating neuroinflammation

Abstract

The invention belongs to the field of biological medicine, and particularly relates to application of an amide compound in preparation of a medicine for treating neuroinflammation. The invention finds that N-[2-[2-(4-chlorphenyl)-4-thiazolyl] ethyl]-butyramide can reduce the NO release of microglial cells, reduce the expression quantity of inflammatory factors TNF-alpha and IL-1beta, and promote the improvement of inflammation phenotypes. On the animal level, the N-[2-[2-(4-chlorphenyl)-4-thiazolyl] ethyl]-butyramide can inhibit activation of small glial cells in nigra and striatum of mice and improve dyskinesia of the mice.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and specifically relates to the application of an amide compound in the preparation of a drug for treating neuroinflammation. Background Art

[0002] Neuroinflammation is a complex physiological response that occurs in the central nervous system due to various triggers, such as infection, trauma, or autoimmune reactions. Characteristics of neuroinflammation include the activation of microglia and astrocytes, and the subsequent release of inflammation-related molecules, including cytokines, chemokines, and nitric oxide. Microglia are resident macrophages of the central nervous system and are the main mediators of neuroinflammation. After sensing damage signals, they undergo morphological and functional changes, which in turn trigger an inflammatory response. In well-regulated neuroinflammation, microglia eliminate pathogens, clear cell debris, and promote tissue repair, and are considered to be a defense mechanism to restore normal function of the central nervous system and maintain homeostasis, but excessive or long-term microglia-mediated neuroinflammation can affect neuronal function and lead to neuronal death.

[0003] N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide (Azoramide) is currently known to improve insulin sensitivity, glucose tolerance and β-cell function, and protect type 2 diabetic mice. Its current application field is mainly in the treatment of diabetes, and there are no reports in the field of drug preparation for the treatment of neuroinflammation. Summary of the invention

[0004] The purpose of the first aspect of the present invention is to provide an application.

[0005] The second aspect of the present invention aims to provide a method.

[0006] In order to achieve the above-mentioned purpose of the present invention, the technical solution adopted by the present invention is:

[0007] The first aspect of the present invention provides the use of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide or a pharmaceutically acceptable salt thereof in a1) to a4):

[0008] a1) preparing products for inhibiting microglia activation;

[0009] a2) Preparation of products for inhibiting neuroinflammation

[0010] a3) Preparation of products for the prevention and treatment of neuroinflammatory diseases;

[0011] a4) Preparation of products for the prevention and treatment of movement disorders.

[0012] The neuroinflammation-related disease includes at least one of Alzheimer's disease, traumatic brain injury, cerebral infarction and multiple sclerosis.

[0013] Neuroinflammation is a condition observed in the central nervous system under the stimulation of infection, toxic metabolites, trauma or autoimmunity, and can occur in central nervous system diseases such as Alzheimer's disease, traumatic brain injury, cerebral infarction and multiple sclerosis.

[0014] The neuroinflammation-related diseases do not include Parkinson's disease.

[0015] The neuroinflammation includes abnormal activation of glial cells and release of inflammatory factors.

[0016] The structural formula of the N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide is:

[0017]

[0018] Preferably, the neurological movement dysfunction comprises a central nervous system movement dysfunction.

[0019] Preferably, the central motor dysfunction does not include Parkinson's disease.

[0020] Preferably, the pharmaceutically acceptable salt includes at least one of a metal salt, an ammonium salt, a salt formed with an inorganic acid, a salt formed with an organic base, a salt formed with an organic acid, a salt formed with a basic amino acid, and a salt formed with an acidic amino acid.

[0021] Preferably, the metal salt comprises an alkali metal salt or an alkaline earth metal salt.

[0022] Preferably, the alkali metal salt includes at least one of a sodium salt and a potassium salt.

[0023] Preferably, the alkaline earth metal salt includes at least one of calcium salt, magnesium salt, barium salt and aluminum salt.

[0024] Preferably, the salt formed with the organic base includes a salt formed with the following organic bases: at least one of trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine and N,N'-dibenzylethylenediamine.

[0025] Preferably, the salt formed with an inorganic acid includes a salt formed with the following inorganic acids: at least one of hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, and phosphoric acid.

[0026] Preferably, the salt formed with the organic acid includes a salt formed with the following organic acids: at least one of formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

[0027] Preferably, the salt formed with a basic amino acid includes a salt formed with the following basic amino acids: at least one of arginine, lysine and ornithine.

[0028] Preferably, the salt formed with the acidic amino acid includes a salt formed with the following acidic amino acids: at least one of aspartic acid and glutamic acid.

[0029] Preferably, the product comprises a pharmaceutical product.

[0030] Preferably, the drug further comprises pharmaceutically acceptable excipients.

[0031] Preferably, the auxiliary material includes at least one of a desiccant, a stabilizer, an antioxidant, a disintegrant, a lubricant, a colorant, a flavoring agent, and a dispersant.

[0032] Preferably, the product may further comprise any one or more second active ingredients.

[0033] Preferably, the subjects to whom the product is administered include animals.

[0034] Preferably, the animal is a mammal; further preferably, the animal is selected from humans, cats, cows, sheep, pigs, dogs, chickens, ducks, geese, rabbits, and mice; even further preferably, the animal is a human, including minors, adults, and the elderly.

[0035] The second aspect of the present invention provides any one of methods b1) to b2), characterized in that cells are treated with N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide or a pharmaceutically acceptable salt thereof:

[0036] b1) Methods for inhibiting microglial activation in vitro for non-therapeutic purposes;

[0037] b2) In vitro method for inhibiting inflammatory substances for non-therapeutic purposes.

[0038] Preferably, the non-therapeutic in vitro inhibition of microglial activation comprises reducing the level of microglial marker protein iba1.

[0039] Preferably, the inflammatory substance includes at least one of NO, TNF-α, and IL-1β.

[0040] Preferably, the cells comprise glial cells.

[0041] Preferably, the glial cells include at least one of astrocytes, microglia, and oligodendrocytes.

[0042] The beneficial effects achieved by the present invention are:

[0043] The present invention found that N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide can reduce the NO release of microglia, reduce the expression of inflammatory factors TNF-α and IL-1β, and promote the improvement of cell inflammation phenotype. At the animal level, N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide can inhibit the activation of microglia in the substantia nigra and striatum of mice and improve the movement disorder of mice. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 The effect of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide on cellular NO release in the LPS inflammation-induced model.

[0045] Figure 2 This is the effect of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide on the expression of cellular TNF-α in the LPS inflammation-induced model.

[0046] Figure 3 This is the effect of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide on the expression of cellular IL-1β in the LPS inflammation-induced model.

[0047] Figure 4 Schematic diagram of the 6-OHDA-induced neuroinflammation model in mice.

[0048] Figure 5 Schematic diagram of body weight changes in mice during 6-OHDA induction.

[0049] Figure 6 The effect of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide treatment on the amount of IBA1 in the substantia nigra of a mouse neuroinflammation model.

[0050] Figure 7 The effect of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide treatment on the amount of Iba1 in the striatum of a mouse neuroinflammation model.

[0051] Figure 8 This is the effect of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide on the climbing ability of mice.

[0052] Fig. 9The effect of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide on the balance ability of mice. DETAILED DESCRIPTION

[0053] The following will be combined with the embodiments to clearly and completely describe the concept of the present invention and the technical effects produced, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0054] The statistical analysis of the present invention is as follows: GraphPad Prism 8 software (GraphPad Software) is used for data processing, and the results are expressed as mean ± standard deviation. One-way analysis of variance is used for statistical analysis, followed by Tukey multiple comparisons. P values ​​less than 0.05 are considered significant. Wherein, "#" represents the significance analysis between the modeling group and the control group, "*" represents the significance analysis between the experimental group and the modeling group, "#" or "*" represents p-value less than 0.05, "##" or "**" represents p-value less than 0.01, and "###" or "***" represents p-value less than 0.001.

[0055] LPS used in the present invention was from Sigma (16529); Azoramide was from MCE (HY-18705); and 6-OHDA was from Sigma (162957).

[0056] Example 1 N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide has anti-inflammatory activity at the cellular level

[0057] 1. Experimental methods

[0058] 1) Cell culture

[0059] The cell culture medium was prepared based on DMEM medium (Gibco, 12800-017) containing 10 v / v% FBS (Gibco, A5256701). BV-2 microglial cells were cultured at a rate of approximately 4×10 5 The cells were cultured in a cell culture incubator at a density of 10 cells / ml, and the cell growth was observed regularly. When the cell adhesion area accounted for about 50-60% of the bottom area of ​​the culture bottle, the cells were digested with trypsin and subcultured, and then continued to be cultured. The 3rd to 7th generation cells were used for experiments.

[0060] 2) Cell treatment

[0061] The experiment was divided into a control group, a modeling group, and an experimental group, with three replicate wells in each group. BV-2 cells in the logarithmic growth phase were taken and inoculated into a 6-well plate with fresh DMEM culture medium containing 10 v / v% serum at a cell density of 5×10 5 cells / ml, inoculated at 1ml / well, and cultured in an incubator at 37°C and 5% CO2. After the cells were cultured for 12 hours, the culture medium was carefully aspirated. According to the experimental groups, the control group used DMEM with 10% serum to incubate the cells, and the modeling group used 1μg / mL LPS in DMEM with 10% serum to treat the cells. The experimental group was treated with 1μg / mL LPS in DMEM with 10% serum and drugs (0.3, 1, 3, 10, 15, 30μM Azoramide) at the same time, and the cells were incubated in a 37°C incubator for 24 hours before experimental operation.

[0062] 3) Determination of nitrite content

[0063] Experimental principle: NO content is generally determined by detecting the content of its stable oxidation product nitrite. The Griess colorimetric method can be used to detect nitroso-NO in the culture medium. 2- The principle of this determination method is that under weak acidic conditions, p-aminobenzenesulfonic acid can react with NO in the solution. 2- The diazotization reaction takes place, and the generated diazonium salt undergoes a coupling reaction with N-(1-naphthyl)-ethylenediamine. The generated azo compound is purple-red, and the product has a large absorption peak at 540-550nm. The absorbance intensity of the product solution at 540nm is measured using an enzyme marker. The absorbance value is consistent with the NO content in the solution. 2- The content of NO is proportional to the 2- content, thus reflecting the change in NO generation.

[0064] Detection method: BV-2 cells in the logarithmic growth phase were inoculated into 6-well plates with fresh DMEM culture medium containing 10% serum at a cell density of 5×10 5 cells / ml, inoculated at 1 ml / well, and cultured in an incubator at 37°C and 5% CO2. After the experimental treatment in step 2), carefully aspirate the culture medium, then take 50 μl of the cell culture supernatant and add it to a 96-well plate, then add 50 μl of Griess reagent (Sigma, G4410-10G), react at room temperature for 15 minutes, and use an enzyme reader to measure the absorbance at 540 nm.

[0065] 4) TNF-α and IL-1β release detection

[0066] Detection method: BV-2 cells in the logarithmic growth phase were inoculated into 6-well plates with fresh DMEM culture medium containing 10 v / v% serum at a cell density of 5×10 5 cells / ml, inoculated at 1 ml / well, and cultured in an incubator at 37°C and 5% CO2. After the cells were cultured for 12 hours, the culture medium was carefully aspirated and treated for 24 hours according to the experiment in step 2). The supernatant was collected and the TNF-α ( EMC001b.96) and IL-1β ( EMC102a.96) content.

[0067] ELISA operation steps: add samples and standards to the antibody-coated ELISA plate (the relevant reagents for ELISA operation are provided by the kit, and the relevant operation methods are shown in the kit manual), incubate at 37°C for 90 minutes, then add biotin-labeled antibodies, incubate for 60 minutes, and then wash 3 times with PBS. Add peroxidase-labeled avidin and incubate for 30 minutes, then wash 5 times, use TMB to develop blue color, and then turn into yellow under the action of acid, and use an ELISA reader to measure the OD value at 450nm. The OD value is positively correlated with the content of inflammatory factors. Use the OD value data of the standard to make a standard curve, and calculate the content of TNF-α and IL-1β in the sample.

[0068] All v / v% above represent volume percentage.

[0069] 2. Experimental results

[0070] The results of the effects of different concentrations of Azoramide on NO release in the LPS cell inflammation model are as follows Figure 1 shown.

[0071] Compared with the control group, the NO release in the modeling group was significantly increased, with a p-value of less than 0.001, proving that the LPS inflammation model was successfully induced. Compared with the modeling group, the NO release in the experimental group decreased with the increase of Azoramide concentration. When the concentration of Azoramide was 1-30 μM, the NO release decreased significantly, with a p-value of less than 0.001.

[0072] The results of the effects of different concentrations of Azoramide on the expression of TNF-α and IL-1β in the LPS cell inflammation model are as follows Figure 2 , 3 shown.

[0073] Compared with the control group, the expression of TNF-α and IL-1β in the modeling group increased significantly, with a p-value of less than 0.001, proving that the LPS inflammation model was successfully induced. Compared with the modeling group, the expression of TNF-α and IL-1β in the experimental group decreased with the increase of Azoramide concentration, and there was a significant difference when the concentration of Azoramide was 1-30μM.

[0074] Example 2 N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide has anti-inflammatory effects at the animal level

[0075] 1. Experimental methods

[0076] 1) Animal husbandry and handling

[0077] Male C57BL / 6J mice aged 8-10 weeks were purchased from the Faculty of Health, University of Macau (Macau, China). The mice were housed under standard conditions (temperature: 22±2°C; 12:12 h light / dark cycle; humidity: 50±5%) with free access to sterile food and water. The mice were acclimatized for 7 days before the experiment. The mice were randomly divided into control group, 6-OHDA, 6-OHDA+0.5 mg / Kg Azoramide and 6-OHDA +5 mg / Kg Azoramide groups, with 6 mice in each group. 6-OHDA injected into the striatum can mediate inflammatory response and cause damage, activate microglial polarization, and can be used to model neuroinflammation caused by nerve injury in mice.

[0078] Before conducting the experiment, the mice must be weighed and recorded. The body weight must be weighed at the same time every day during the experiment until the mice are killed and sampled.

[0079] In the 6-OHDA group, 10 μg of 6-OHDA was injected into the striatum of mice by stereotaxic injection, while the control group was injected with saline (without other solvent components). The specific method was as follows: the upper incisors of the mouse were inserted into the horizontal bar of the stereotaxic injection instrument (kdScientific, 78-8130), and the nose bar was pressed tightly by adjusting the knob; the ear bar was inserted into the ear canal of the mouse, and the left and right ear bars were balanced and adjusted so that the line between the two ears of the mouse was in the same straight line with the ear bar. After ensuring that the scale positions of the left and right ear bars were the same, the knob was adjusted to lock the ear bar. After cutting off the top hair of the mouse, it was disinfected with iodine or alcohol, the scalp was cut longitudinally, the skin was separated from the left and right with hemostats, and the periosteum of the skull was scraped off with a blade, or the periosteum of the skull was corroded with hydrogen peroxide. After completely removing the periosteum, the Bregma point was revealed. The value of the Bregma point was read with a brain locator as the origin of the three-dimensional coordinate O. Starting from the Bregma point, move vertically backward 0.6mm, then move sideways about 1.2mm, and downward about 4mm to enter the striatum. Use a 10uL micro-syringe, the injection dose is 3μL (10μg / 3μL unilateral injection), the injection time is about 10 minutes, stay for 10 minutes after injection, and then slowly pull out the syringe needle.

[0080] In the 6-OHDA+0.5mg / Kg Azoramide group and the 6-OHDA+5mg / Kg Azoramide group, each mouse was intraperitoneally injected with Azoramide once, while the control group was intraperitoneally injected with solvent (40v / v% saline, 40v / v% PEG300, 20v / v% DMSO). After 12 hours, each mouse was stereotaxically injected into the striatum using the above procedure. The experimental process is as follows Figure 4 Wherein v / v% indicates volume percentage.

[0081] 2) Animal sampling operation

[0082] After 7 days, behavioral studies were performed for 3 consecutive days (behavior-related operations and data are shown in Example 3). After the last behavioral test, mice were deeply anesthetized by inhalation of isoflurane (Rayward, 217180801), and then whole body perfusion was performed using 4wt% paraformaldehyde. The needle of the infusion set No. 4 and a half was used when perfusion fixed the mice. The needle was inserted from the heart axis direction, pierced into the apex of the heart by about 3 to 4 mm, the right atrial appendage was cut, and about 40 ml of normal saline was perfused, and about 20 ml of 4wt% paraformaldehyde was perfused. After the perfusion is completed, the epidermis on the back of the mouse is peeled off, the mouse skull is fixed at the eye socket with hook forceps, and the skull and cervical vertebrae are cut with tissue scissors. The scissors are inserted into the foramen magnum and close to the bone scissors. The scissors are inserted from the foramen magnum and close to the bone scissors toward the ipsilateral eye socket. Cut to the eye socket. The right side is the same as above. Cut from between the mouse eye sockets. Hold the hook forceps with the left hand and insert them into the mouse eye socket to fix the skull. Use curved forceps to directly clamp the bone at the foramen magnum and lift it up directly to expose the complete brain tissue. Push the brain tissue upward from the cerebellum, cut the cranial nerves, and then peel off the whole brain. Quickly remove the whole brain, place it in 4wt% paraformaldehyde, fix it for 16 hours, and then place it in 30wt% sucrose solution for dehydration for 24 hours. All mice were randomly assigned by personnel independent of the author and experimenter to receive treatment in a blinded manner. The experimenter was unaware of the treatment. All animal procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the Ethics Committee of the University of Macau (approval number UMARE 012 2022).

[0083] 3) Immunofluorescence staining

[0084] The whole brain embedded in OCT (SAKURA, 4583) was cut into 30 μm thick slices using a freezing microtome (Thermo, NX70), placed in PBST (PBS containing 0.3 v / v% Triton X-100), blocked at room temperature for 1 hour using immunostaining blocking solution (Beyotime, P0102), incubated with anti-iba1 (Wako Pure Chemical Industries, Ltd., 019-19741, 1:1000) antibody at 4°C overnight, washed 3 times with PBST, incubated with immunofluorescence secondary antibody (Invitrogen) at room temperature for 1 hour, washed 3 times with PBST, added with antifade mounting agent (Sigma, F6182) and covered with a cover glass, observed and photographed under a fluorescence microscope (Leica, 601553). All v / v% above represent volume percentages.

[0085] 2. Experimental results

[0086] The body weight of mice treated with different experiments Figure 5 shown.

[0087] The fluorescence results of iba1 in the substantia nigra of mice after different experimental treatments are as follows Figure 6The fluorescence intensity of iba1 in the substantia nigra of the model group mice increased significantly, while 5 mg / Kg of Azoramide treatment significantly reduced the expression of iba1 in the substantia nigra of the mice, indicating that the activation of microglia in the substantia nigra of the mice was significantly reduced.

[0088] The fluorescence results of Iba1 in the striatum of mice after different experimental treatments are shown in Figure 2. Figure 7 The fluorescence intensity of iba1 in the striatum of the modeling group mice increased significantly, while 5 mg / Kg of Azoramide treatment significantly reduced the expression of iba1 in the striatum of the mice, indicating that the activation of microglia in the striatum of mice was significantly reduced.

[0089] In the case of neuroinflammation, microglia undergo rapid changes in gene expression, morphology, and function, and these reactions are collectively referred to as microglial polarization. LPS-induced activated microglia are classically activated (M1 phenotype), and M1 microglia will release high levels of the above-mentioned inflammatory factors and neurotoxins, leading to uncontrolled inflammatory responses, aggravating tissue damage and neuronal death.

[0090] The results of this example show that after Azoramide treats mice, it can penetrate the blood-brain barrier, reduce the activation of M1 microglia, and significantly reduce the neuroinflammatory phenotype of mice.

[0091] Example 3 N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide improves animal movement disorders

[0092] 1. Experimental methods

[0093] 1) Mouse modeling

[0094] See Example 2.

[0095] 2) Behavioral testing

[0096] Pole climbing test: The pole climbing test is a classic method for evaluating the motor coordination ability of mice. By recording the time required for the mouse to climb from the top of the pole to the bottom (with both front paws on the ground), its motor ability can be compared. A homemade pole with a length of 50 cm and a diameter of 1 cm is wrapped with gauze to increase friction and prevent the mouse from slipping. Place the climbing pole vertically in the animal cage, and place the mouse head down on the top of the pole. Record the time it takes for the mouse to climb from the top to the bottom platform. Test three times, with an interval of 30 minutes each time, and take the average value. If the mouse stops halfway or crawls in the opposite direction, it will not be recorded and will be measured again. For mice that cannot hold the pole and slide down completely naturally, the climbing time is recorded as 60 seconds.

[0097] Rotarod test: The rotarod test provides a convenient method to detect the motor function of rodents. By measuring the duration of the animal's walking on the roller, its motor ability can be compared. The mouse rotarod fatigue instrument (Zhongshi Technology) was used for testing. The mouse was placed on the rotarod fatigue instrument, and the initial speed was set to 10 rpm. The speed increased by 5 rpm every 15 seconds, with 40 rpm as the maximum speed. The test duration was 4 minutes, and the length of time the mouse was on the rod was recorded. Each mouse was tested 3 times, with an interval of 30 minutes each time, and the average value was taken.

[0098] 2. Experimental results

[0099] Schematic diagram and experimental results of the mouse climbing pole experiment are shown in Figure 8 Compared with the control group, the time taken by the mice in the modeling group to climb from the top pole to the bottom was significantly prolonged by about two times, while the time taken by the mice to climb the pole after modeling was significantly shortened after the mice were treated with 5mg / Kg Azoramide, which was close to that of the control group.

[0100] Schematic diagram of the mouse rotarod test and the experimental results are shown in Fig. 9 Compared with the control group, the balance ability of the mice in the modeling group was significantly decreased, while the time of the mice on the rod after modeling was significantly prolonged after the treatment of 5mg / Kg Azoramide, which was close to that of the control group.

[0101] In summary, the motor ability of mice treated with Azoramide after the end of the inflammation model was close to that of the control group, with no significant decrease. Azoramide has the effect of preventing motor dysfunction in mice caused by neuroinflammation.

Claims

1. Use of N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide or a pharmaceutically acceptable salt thereof in a1) to a4): a1) preparing products for inhibiting microglia activation; a2) preparing products for inhibiting neuroinflammation; a3) Preparation of products for the prevention and treatment of neuroinflammatory diseases; a4) Preparation of products for the prevention and treatment of movement disorders.

2. The use according to claim 1, characterized in that: The neuroinflammation includes abnormal activation of glial cells and release of inflammatory factors.

3. The use according to claim 2, characterized in that: The movement dysfunction includes neurological movement dysfunction; Preferably, the neurological motor dysfunction comprises central nervous system motor dysfunction; Preferably, the central motor dysfunction does not include Parkinson's disease.

4. The use according to claim 3, characterized in that: The pharmaceutically acceptable salt includes at least one of a metal salt, an ammonium salt, a salt formed with an inorganic acid, a salt formed with an organic base, a salt formed with an organic acid, a salt formed with a basic amino acid, and a salt formed with an acidic amino acid; Preferably, the metal salt comprises an alkali metal salt or an alkaline earth metal salt; Preferably, the alkali metal salt includes at least one of a sodium salt and a potassium salt; Preferably, the alkaline earth metal salt comprises at least one of calcium salt, magnesium salt, barium salt and aluminum salt; Preferably, the salt formed with the organic base includes a salt formed with the following organic bases: at least one of trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, and N,N'-dibenzylethylenediamine; Preferably, the salt formed with the inorganic acid includes a salt formed with the following inorganic acids: at least one of hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, and phosphoric acid; Preferably, the salt formed with the organic acid comprises a salt formed with the following organic acids: at least one of formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; Preferably, the salt formed with a basic amino acid includes a salt formed with the following basic amino acids: at least one of arginine, lysine, and ornithine; Preferably, the salt formed with the acidic amino acid includes a salt formed with the following acidic amino acids: at least one of aspartic acid and glutamic acid.

5. The use according to claim 4, characterized in that: The products include pharmaceutical products; Preferably, the drug further comprises a pharmaceutically acceptable excipient; Preferably, the auxiliary material includes at least one of a desiccant, a stabilizer, an antioxidant, a disintegrant, a lubricant, a colorant, a flavoring agent, and a dispersant.

6. The use according to claim 5, characterized in that: The product may also include any one or more second active ingredients.

7. The use according to claim 6, characterized in that: The subjects of administration of the product include animals, Preferably, the animal is a mammal; further preferably, the animal is selected from humans, cats, cows, sheep, pigs, dogs, chickens, ducks, geese, rabbits, and mice; even further preferably, the animal is a human, including minors, adults, and the elderly.

8. Any of the methods b1) to b2), characterized in that: Treating cells with N-[2-[2-(4-chlorophenyl)-4-thiazolyl]ethyl]-butyramide or a pharmaceutically acceptable salt thereof: b1) Methods for inhibiting microglial activation in vitro for non-therapeutic purposes; b2) In vitro method for inhibiting inflammatory substances for non-therapeutic purposes.

9. The method according to claim 8, characterized in that: The in vitro non-therapeutic inhibition of microglial activation includes reducing the level of microglial marker protein iba1; The inflammatory substance includes at least one of NO, TNF-α, and IL-1β.

10. The method according to claim 9, characterized in that: The cells include glial cells; Preferably, the glial cells include at least one of astrocytes, microglia, and oligodendrocytes.

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