Application of CSF1R inhibitor in preparation of preparation for improving imbalance of intestinal flora

Abstract

The invention discloses an application of a CSF1R inhibitor in preparation of a preparation for improving intestinal flora imbalance of a subject or treating and / or preventing intestinal flora imbalance related diseases of the subject, and the CSF1R inhibitor can regulate intestinal flora in the aspects of Alpha diversity, Beta diversity, gate-level mouse intestinal flora structure, family-level mouse intestinal flora structure and the like. The pharmaceutical composition has a preparation developed to improve intestinal flora imbalance of a subject, or treat and / or prevent diseases related to the intestinal flora imbalance of the subject.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and in particular to application of a CSF1R inhibitor in preparing a preparation for improving intestinal flora imbalance. Background Art

[0002] The intestinal flora and the host are in a state of mutual symbiosis and dynamic equilibrium. The intestinal flora is mainly composed of anaerobic bacteria, facultative anaerobic bacteria and aerobic bacteria. It produces a variety of vitamins and enzymes required by the body, participates in the digestion and metabolism of nutrients, and also produces antimicrobial peptides such as defensins, C-type lectins, and antimicrobial peptides, which protect the body from pathogen invasion and play a vital role in maintaining the health of the host. In addition, short-chain fatty acids (SCFA), an important metabolite of the intestinal flora, can act on proinflammatory cytokines, inhibit inflammatory responses, and maintain the integrity and homeostasis of the intestinal mucosa. Genetics, environment, diet, disease, antibiotics and other factors can all lead to intestinal flora imbalance, which is manifested as changes in the composition and structure of the intestinal flora and abnormal diversity; pathogenic and conditionally pathogenic microorganisms dominate; intestinal barrier dysfunction, increased intestinal wall permeability, bacterial translocation into the systemic circulation, and then induce inflammatory responses and metabolic disorders in the body.

[0003] The proportion of high-fat diet in people's daily diet is gradually increasing. Long-term intake of high-fat food will cause a variety of pathological changes, such as hyperinsulinemia, insulin resistance, dyslipidemia, overstimulation of the sympathetic nervous system, systemic inflammation, hyperglycemia, endotoxemia, increased reactive oxygen species and oxidative stress. A high-fat diet will change the composition of the intestinal microbiota. Studies have shown that a high-fat diet will reduce the number of beneficial bacteria in the intestines, such as Bifidobacterium and Lactobacillus, while increasing potentially harmful bacteria, such as sulfate-reducing bacteria (Desulfovibrio), or causing abnormal changes in the composition ratio of the original microbiota. This change in the structure of the microbial community may be related to the development of chronic diseases such as obesity, diabetes, and inflammatory bowel disease. Secondly, a high-fat diet may also promote cancer progression through metabolic disorders caused by intestinal microbiota, such as increasing the number of Desulfovibrio in the intestine, promoting the progression or recurrence of malignant tumors such as breast cancer and melanoma. In addition, a high-fat diet may also affect the metabolism and health of the host by affecting the metabolites of the intestinal microbiota. For example, a high-fat diet reduces the production of short-chain fatty acids, which have anti-inflammatory effects and may help improve diabetes and obesity. Therefore, it is of great significance to provide a substance that can regulate the intestinal flora imbalance caused by a high-fat diet.

[0004] CSF1R is a tyrosine kinase transmembrane receptor and a member of the growth factor CSF1 / platelet-derived growth factor (PDGF) receptor family that exhibits intrinsic tyrosine-specific protein kinase activity. CSF1R is involved in the survival, proliferation, differentiation, recruitment and function of mononuclear phagocytes (such as macrophages and monocytes). PLX3397, chemical name Pexidartinib, also known as Pexidartinib, is a potent, orally active, selective and ATP-competitive CSF1R inhibitor. The molecular formula of the compound is C 20 H 15 CIF 3 N 5 , molecular weight: 417.81, CAS number: 1029044-16-3, PLX3397 has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of tenosynovial giant cell tumors. Studies have shown that PLX3397 can reprogram tumor-associated macrophages (TAMs) and stimulate T cells to infiltrate into the tumor microenvironment. In one study, PLX3397 significantly inhibited the growth and lung metastasis of primary tumors, thereby improving metastasis-free survival. In addition, in a mouse model, PLX3397 can reduce tissue macrophage levels without affecting glucose homeostasis, showing its potential in regulating the immune microenvironment. So far, there have been no reports on the role of CSF1R inhibitors in regulating the imbalance of intestinal flora caused by a high-fat diet. Summary of the invention

[0005] The present invention aims to solve at least one of the above-mentioned technical problems existing in the prior art. To this end, the present invention aims to provide a use of a CSF1R inhibitor in the preparation of a preparation for improving intestinal flora imbalance.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] The present invention provides the use of a CSF1R inhibitor in the preparation of a preparation for improving intestinal flora imbalance in a subject, or treating and / or preventing a disease related to intestinal flora imbalance in a subject.

[0008] In one or more embodiments, the CSF1R inhibitor is PLX3397 or a stereoisomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, polymorph, cocrystal, solvate, stable isotope derivative, metabolite or prodrug thereof. The structural formula of PLX3397 is

[0009]

[0010] In one or more embodiments, the subject has at least one of the following characteristics:

[0011] (1) The subjects' intestinal flora imbalance was caused by a high-fat diet;

[0012] (2) The observed_otus, Chao1 index, Shannon index, and Pielou-e index of the subjects' intestinal flora alpha diversity index decreased;

[0013] (3) The abundance of Bacteroidetes, Verrucomicrobiota, and Desulfobacterota in the subjects' intestines was higher than that in the normal population; the abundance of Firmicutes in the subjects' intestines was lower than that in the normal population;

[0014] (4) The abundance of Akkermansiaceae, Desulfovibrionaceae, and Prevotellaceae in the subjects' intestines was higher than that in the normal population; the abundance of Lachnospiraceae and Muribaculaceae in the subjects' intestines was lower than that in the normal population;

[0015] (5) The abundance of Verrucomicrobiota, Verrucomicrobiae, and Akkermansiaceae in the subjects' intestines was higher than that in the normal population; the abundance of Firmicutes, Clostridia, and Lachnospirales in the subjects' intestines was lower than that in the normal population;

[0016] Among them, the normal group refers to a healthy group that does not follow a high-fat diet.

[0017] In one or more embodiments, improving the imbalance of intestinal flora in the subject comprises at least one of the following:

[0018] (1) Improve the observed_otus, Chao1 index, Shannon index, and Pielou-e index in the subjects' intestinal flora alpha diversity index;

[0019] (2) increase the abundance of Firmicutes in the intestinal flora of the subjects and decrease the abundance of Bacteroidetes and / or Verrucomicrobia in the intestinal flora of the subjects;

[0020] (3) increasing the abundance of Lachnospiraceae and / or Rhabditiaceae in the intestinal flora of the subjects, and decreasing the abundance of Akkermansiaceae, Desulfovibrioaceae, and / or Prevotellaceae in the intestinal flora of the subjects;

[0021] (4) increasing the abundance of Bacteroidetes, Bacteroides and / or Europhila in the intestinal flora of the subjects, and decreasing the abundance of Akkermansia and / or Akkermansia in the intestinal flora of the subjects.

[0022] In one or more embodiments, the related diseases include at least one of abnormal glucose and lipid metabolism diseases, gastrointestinal diseases, cardiovascular diseases, and mental and nervous system diseases.

[0023] In one or more embodiments, the abnormal glucose and lipid metabolism disease comprises at least one of obesity, obesity complications, diabetes, and diabetic complications.

[0024] In one or more embodiments, the gastrointestinal disease comprises at least one of inflammatory bowel disease, irritable bowel syndrome, and celiac disease.

[0025] In one or more embodiments, the cardiovascular disease comprises at least one of coronary heart disease, heart failure, hypertension, atrial fibrillation, acute myocardial infarction, and coarctation of the aorta.

[0026] In one or more embodiments, the psychiatric and neurological disorders comprise at least one of anxiety, depression, epilepsy, ALS, autism, or progeria.

[0027] In one or more embodiments, the preparation is any one of a medicine, a health product, a special medical food, a health functional food, a beverage and a feed.

[0028] In one or more embodiments, the preparation further comprises at least one acceptable excipient.

[0029] In one or more embodiments, the formulation is a pharmaceutical product.

[0030] In one or more embodiments, the dosage form of the drug is any one of tablets, capsules, lozenges, hard candies, powders, sprays, creams, ointments, suppositories, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, and syrups.

[0031] In one or more embodiments, the drug is administered orally, intravenously, intraarterially, subcutaneously, intraperitoneally, intramuscularly or transdermally.

[0032] The beneficial effects of the present invention are as follows: the present invention provides a new application of CSF1R inhibitors in regulating intestinal flora imbalance. CSF1R inhibitors can regulate the intestinal flora in terms of Alpha diversity, Beta diversity, phylum-level mouse intestinal flora structure, family-level mouse intestinal flora structure, etc., and can be developed into preparations for improving intestinal flora imbalance in subjects, or treating and / or preventing diseases related to intestinal flora imbalance in subjects. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 The figure shows the effect of PLX3397 on the body weight and blood biochemical indexes of mice fed a high-fat diet. LDL-C is Low-Density Lipoprotein Cholesterol; TG is Triglycerides; TP is Total Protein; ALP is Alkaline Phosphatase; ALB is Albumin; UA is Uric Acid.

[0034] Figure 2 Beta diversity analysis results of the effect of PLX3397 on the intestinal flora of mice fed a high-fat diet.

[0035] Figure 3 It is the dominant bacterial flora at the phylum level of the intestinal flora of each group of mice.

[0036] Figure 4 It is the dominant bacterial flora at the family level in the intestinal flora of each group of mice.

[0037] Figure 5 Analyze cladograms for LEfSe.

[0038] Figure 6 It is the LDA distribution histogram based on LEfSe analysis. DETAILED DESCRIPTION

[0039] The present invention is further described in detail below by specific examples. Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial sources or can be obtained by prior art methods. Unless otherwise specified, the experiments or test methods are conventional methods in the art.

[0040] The test materials involved in the embodiments of the present invention are as follows:

[0041] 1. Instruments: veterinary fully automatic biochemical analyzer (BS-240VET), normal temperature centrifuge (Eppendorf Centrifuge 5424), refrigerated centrifuge (Microfuge R 22R Centrifuge), vortex shaker (Huali Da WH-861 Vortex Shaker), three-temperature three-control constant temperature water bath (Shanghai Boxun Industrial Co., Ltd. DK-8D), PCR instrument (Hangzhou Langji Scientific Instrument Co., Ltd. A200 gene amplification instrument), electrophoresis instrument (Tanon Tianneng R EPS300), gel imager (Tanon-2500), ultra-low temperature freezing storage box (Zhongke Meiling Cryogenic Technology Co., Ltd. DW-HL388), fully automatic sample rapid grinding instrument (Shanghai Jingxin JXFSTPRP-96L).

[0042] 2. Reagents: PLX3397 (MedChemExpress), Pusion Hot start flex 2X Master Mix (Shanghai Yitao Biological Instrument Co., Ltd., M0536L), DL2000 DNA Maker (Takara, 3427A), Gene colour (Beijing Jinboyi, GBY-1), Qubit dsDNA HS Assay Kit (500 times) (Invitrogen, Life technologies, Q3285) 4, Biowest Agarose G-10 (BIOWEST, 111860), 50xTAE Buffer (Shanghai Biotech, B548101-500), AMPure XT beads (Beckman, A63880).

[0043] 3. Animals: 30 SPF-grade C57BL / 6 female mice, 7 weeks old, weighing about 18-20g. SPF is the abbreviation for Specific-pathogen-free, which means that animals do not carry specific pathogens and parasites that may interfere with the experiment. They need to be kept in a barrier system and implement strict microbial and parasite control.

[0044] 4. Feed: high-fat feed (Jiangsu Medison Biotechnology Co., Ltd., 60% fat, MD12033).

[0045] Example 1 Effect of PLX3397 on high-fat diet mice

[0046] Experimental methods

[0047] The mice in the normal group (Con) were fed with ordinary feed, and the mice in the model group (Mod) and the treatment group (Ptreat) were fed with high-fat feed. At the 14th week of feeding, the mice in the treatment group were gavaged with 5% Tween-80 aqueous solution (50 mg / kg) of PLX3397 every other day, and the mice in the normal group and the model group were gavaged with an equal volume of 5% Tween-80 aqueous solution for 4 weeks. After the last administration, the mice in each group were fasted but not watered for 12 hours, and blood was collected to measure biochemical indicators (LDL-C, TG, TP, ALP, ALB, UA), and the contents of the ileocecal part were collected, and the intestinal flora of each group of mice was detected by 16SrRNA sequencing.

[0048] Experimental Results

[0049] 1. Effects of PLX3397 on body weight and blood biochemical indexes of mice fed a high-fat diet

[0050] from Figure 1 The results showed that compared with the control (Con) group, the model (Mod) group had significantly higher TG and UA indicators (P<0.001) ( Figure 1 Middle C, Figure 1 D), TP and ALP indexes were significantly decreased (P<0.001) ( Figure 1 Middle E, Figure 1 G), the ALB index was significantly decreased (P<0.05) ( Figure 1 (middle B).

[0051] Compared with the mice in the model (Mod) group, the UA index of the mice in the PLX3397 group (Ptreat) was significantly reduced (P<0.01) ( Figure 1 D), the ALB, ALP, TP and TG indexes showed a clear trend of recovery to the normal diet mice Con group ( Figure 1 Middle B, Figure 1 Middle E, Figure 1 Medium G, Figure 1 Middle C).

[0052] Table 1

[0053] Con Mod Ptreat ALB(g / L) 33.19±0.47 31.82±0.33* 32.63±0.71 ALP(U / L) 141.64±5.78 72.52±3.44*** 94.36±7.11 TG (mmol / L) 0.66±0.06 1.03±0.10*** 0.91±0.09 TP(g / L) 49.96±0.48 42.72±0.49*** 43.66±1.36 UA (μmol / L) 169.66±17.61 225.60±15.31** 149.97±13.75##

[0054] Note: “*” indicates that compared with the control group, P<0.05; “***” indicates that compared with the control group, P<0.001; “#” indicates that compared with the model group, P<0.05.

[0055] 2. Effect of PLX3397 on intestinal flora of mice fed a high-fat diet

[0056] After DNA extraction from stool samples, the variable region (V3-V4) was amplified using upstream primer 341F (5′-CCTACGGGNGGCWGCAG-3′, SEQ ID NO. 1) and downstream primer 805R (5′-GACTACHVGGGTATCTAATCC-3′, SEQ ID NO. 2). After purification, the amplified DNA was evaluated using an Agilent 2100 bioanalyzer (Agilent, USA) and a library quantification kit for Illumina (Kapa Biosciences, Woburn, MA, USA). Qualified amplified products were sequenced at 2×250 bp using a NovaSeq 6000 sequencer and clustered according to a similarity of 97% to obtain operational taxonomic units (OTUs).

[0057] Alpha diversity refers to the diversity within a specific environment or ecosystem, which is mainly used to reflect species richness and uniformity as well as sequencing depth, and is mainly reflected by Chao1, observed_otus, Goods_coverage, Shannon, Simpson and Pielou-e indices. OTUs refers to operational taxonomic units.

[0058] According to the results in Tables 2 and 3, the Goods-coverage index of each group of samples was greater than 0.99, indicating that the sequencing results were good and could reflect the microbial community of each sample. Compared with the control (Con) group, the observed_otus and Chao1 indices of mice in the model (Mod) group were significantly reduced (P<0.05), and the Shannon and Pielou-e indices were extremely significantly reduced (P<0.001).

[0059] Compared with the mice in the model (Mod) group, the PLX3397 group (Ptreat) mice had a certain regulatory effect on various indexes, making them close to the various indices of the Alpha diversity of the intestinal flora of the mice in the control (Con) group.

[0060] Table 2: Alpha diversity analysis results of intestinal flora of mice in each group

[0061]

[0062] Note: Data represent (x±SEM), "*" indicates P<0.05 compared with the control group; "***" indicates P<0.001 compared with the control group; "#" indicates P<0.05 compared with the model group.

[0063] Table 3: Alpha diversity analysis results of intestinal flora of mice in each group

[0064]

[0065] Note: Data represent (x±SEM), "***" indicates P<0.001 compared with the control group.

[0066] Beta diversity refers to the species differences between different environmental communities. In the principal coordinate analysis PCoA diagram and the principal component analysis PCA diagram, the samples in each group were able to cluster significantly, indicating that the intestinal flora within each group of samples tended to be consistent. The flora structure composition of the Con group and the Mod group was significantly different (P<0.05), indicating that the high-fat diet caused the intestinal flora structure of mice to be disordered; compared with the Mod group, the samples in the Ptreat group were more closely distributed in the PcoA cluster and deviated from the Mod group, indicating that PLX3397 administration had a regulatory effect on the intestinal flora structure. Results are shown in Figure 2 .

[0067] Changes in the structure of the intestinal flora of mice at the phylum level: The dominant flora at the phylum level of the intestinal flora of each group of mice are as follows Figure 3 As shown. At the phylum level, Firmicutes and Bacteroidetes were the main species in the intestinal flora of the Con group, with a total abundance of more than 80%; compared with the Con group, the abundance of Firmicutes in the Mod group was significantly reduced, and the abundance of Bacteroidetes, Verrucomicrobiota, and Desulfobacterota increased; compared with the Mod group, the abundance of Firmicutes in the Ptreat group increased, and the abundance of Proteobacteria, Desulfobacterota, Bacteroidetes, and Verrucomicrobiota decreased, approaching the level of the Con group. This indicates that the administration of PLX3397 restored the relative abundance of Bacteroidetes, Firmicutes, and Verrucomicrobiota in the intestinal flora of mice fed a high-fat diet to the level of the intestinal flora structure of healthy mice.

[0068] Changes in the structure of the intestinal flora of mice at the family level: The dominant flora at the family level of the intestinal flora of each group of mice are as follows: Figure 4At the family level, Lachnospiraceae and Muribaculaceae were the main families in the intestinal flora of the Con group, with an abundance of more than 10%; compared with the Con group, the abundance of these two families in the Mod group decreased significantly, while the abundance of Akkermansiaceae, Desulfovibrionaceae, and Prevotellaceae increased; compared with the Mod group, the abundance of Akkermansiaceae, Desulfovibrionaceae, and Prevotellaceae decreased in the Ptreat group, while the abundance of Lachnospiraceae and Muribaculaceae increased. This indicates that the administration of PLX3397 restored the relative abundance of Akkermansiaceae, Desulfovibrioaceae, Prevotellaceae, Lachnospiraceae and Bacillusaceae in the intestinal flora of mice fed a high-fat diet to the level of the intestinal flora structure of healthy mice.

[0069] The evolutionary branch diagram was analyzed by LEfSe (LDA Effect Size analysis, which is an analytical tool used to discover and explain differences in biological markers (such as genes, pathways, and taxa) in high-dimensional data) to further determine the differential bacterial community information closely related to the regulatory effect of PLX3397. Figure 5 It can be seen that the circles radiating from the inside to the outside in the LEfSe evolutionary branch diagram represent the classification level from phylum to genus. Each small circle represents a classification at that classification level, and its diameter is positively correlated with the relative abundance. Species with no significant differences are shown in yellow, and the differential biomarkers of each group in the experiment are shown in red (Con group), green (Mod group) and blue (Ptreat group). Figure 6 The LDA distribution histogram based on LEfSe analysis is shown, indicating the biomarkers with significant differences in abundance (LDA>3, P<0.05) in different groups. The length of the histogram in the figure represents the degree of influence of the biomarkers with significant differences. The results showed that there were 13, 8 and 4 statistically different bacterial families in the Con group, Mod group and Ptreat group respectively (LDA>3, P<0.05).

[0070] The results of LEfSe analysis showed that compared with the Con group, the abundance of Verrucomicrobiota, Verrucomicrobiae, and Akkermansiaceae in the Mod group increased, while the abundance of Firmicutes, Clostridia, and Lachnospirales decreased; after the administration of PLX3397, the number and abundance of intestinal flora in mice fed a high-fat diet were significantly increased in the intestines of mice fed a high-fat diet. Compared with the Mod group, the abundance of Bacteroidaceae, Bacteroides, and Olsenella in the Ptreat group increased, while the abundance of Akkermansiaceae and Akkermansia decreased. Bacteroidetes and Bacteroides are the main bacteria in the intestine that break down complex carbohydrates. They help produce short-chain fatty acids, which are very important for maintaining intestinal homeostasis, have anti-inflammatory effects, and can inhibit the release of pro-inflammatory cytokines, thereby helping to prevent and alleviate inflammatory bowel disease; the increase in Eurosinella can regulate and enhance immunotherapy responses by producing the metabolite inosine, helping the immune system to fight cancer tumors more effectively. Akkermansia and Akkermansia increased abnormally in the intestines of mice fed a high-fat diet, disrupting the balance of the intestinal microbiota of normal mice. After the administration of PLX3397, the abundance of this type of bacteria decreased and the intestinal microbiota structure of healthy control mice was restored.

[0071] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. Use of a CSF1R inhibitor in the preparation of a preparation for improving intestinal flora imbalance in a subject, or treating and / or preventing a disease related to intestinal flora imbalance in a subject.

2. The use according to claim 1, characterized in that: The CSF1R inhibitor is PLX3397 or a stereoisomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, polymorph, cocrystal, solvate, stable isotope derivative, metabolite or prodrug thereof.

3. The use according to claim 1, characterized in that: The subject has at least one of the following characteristics: (1) The subjects' intestinal flora imbalance was caused by a high-fat diet; (2) The observed_otus, Chao1 index, Shannon index, and Pielou-e index of the subjects' intestinal flora alpha diversity index decreased; (3) The abundance of Bacteroidetes, Verrucomicrobiota, and Desulfobacterota in the subjects' intestines was higher than that in the normal population; the abundance of Firmicutes in the subjects' intestines was lower than that in the normal population; (4) The abundance of Akkermansiaceae, Desulfovibrionaceae, and Prevotellaceae in the subjects' intestines was higher than that in the normal population; the abundance of Lachnospiraceae and Muribaculaceae in the subjects' intestines was lower than that in the normal population; (5) The abundance of Verrucomicrobiota, Verrucomicrobiae, and Akkermansiaceae in the intestines of the subjects was higher than that in the intestines of the normal group; the abundance of Firmicutes, Clostridia, and Lachnospirales in the intestines of the subjects was lower than that in the intestines of the normal group.

4. The use according to claim 1, characterized in that: Improving the imbalance of intestinal flora in the subject includes at least one of the following: (1) Improve the observed_otus, Chao1 index, Shannon index, and Pielou-e index in the subjects' intestinal flora alpha diversity index; (2) increase the abundance of Firmicutes in the intestinal flora of the subjects and decrease the abundance of Bacteroidetes and / or Verrucomicrobia in the intestinal flora of the subjects; (3) increasing the abundance of Lachnospiraceae and / or Rhabditiaceae in the intestinal flora of the subjects, and decreasing the abundance of Akkermansiaceae, Desulfovibrioaceae, and / or Prevotellaceae in the intestinal flora of the subjects; (4) increasing the abundance of Bacteroidetes, Bacteroides and / or Europhila in the intestinal flora of the subjects, and decreasing the abundance of Akkermansia and / or Akkermansia in the intestinal flora of the subjects.

5. The use according to claim 1, characterized in that: The related diseases include at least one of abnormal glucose and lipid metabolism diseases, gastrointestinal diseases, cardiovascular diseases, and mental and nervous system diseases.

6. The use according to claim 5, characterized in that: The abnormal glucose and lipid metabolism disease includes at least one of obesity, obesity complications, diabetes, and diabetic complications; Preferably, the gastrointestinal disease comprises at least one of inflammatory bowel disease, irritable bowel syndrome, and celiac disease; Preferably, the cardiovascular disease comprises at least one of coronary heart disease, heart failure, hypertension, atrial fibrillation, acute myocardial infarction, and aortic coarctation; Preferably, the psychiatric and neurological disorders include at least one of anxiety, depression, epilepsy, ALS, autism or progeria.

7. The use according to claim 1, characterized in that: The preparation is any one of medicines, health products, special medical foods, health functional foods, beverages and feeds.

8. The use according to claim 1, characterized in that: The preparation further comprises at least one acceptable excipient.

9. The use according to claim 1, characterized in that: The preparation is a medicine.

10. The use according to claim 9, characterized in that: The dosage form of the drug is any one of tablets, capsules, lozenges, hard candies, powders, sprays, creams, ointments, suppositories, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, and syrups; Preferably, the drug is administered orally, intravenously, intraarterially, subcutaneously, intraperitoneally, intramuscularly or transdermally.

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