A nutrient composition for preventing and / or treating post-traumatic stress disorder

Abstract

This invention belongs to the field of biomedical technology, and specifically relates to a nutrient composition for the prevention and / or treatment of post-traumatic stress disorder (PTSD). This invention utilizes metabolomics technology to screen and identify metabolite changes occurring during the pathophysiological process of PTSD, and then designs a nutrient composition comprising five components: α-ketoglutarate, thiamine hydrochloride, L-serine, L-tryptophan, and L-tyrosine. Combined supplementation of these five nutrient components effectively improves anxiety-like behavior and promotes the extinction of fear memories in PTSD model mice. Furthermore, the nutrient composition of this invention exhibits extremely high safety, with side effects far lower than traditional chemically synthesized drugs, and is expected to improve long-term patient adherence.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and in particular relates to a nutrient composition for the prevention and / or treatment of post-traumatic stress disorder. Background Technology

[0002] Post-traumatic stress disorder (PTSD) is a chronic, disabling mental disorder that can occur after experiencing or witnessing a severe traumatic event. Its core symptoms encompass four main categories: recurrent re-experiencing of the trauma, persistent avoidance of the associated stimuli, widespread negative changes in cognition and emotion, and significantly increased vigilance and startle reflex. These symptoms severely impair an individual's social functioning and quality of life, and significantly increase the risk of other mental disorders, self-harm, and suicidal behavior. Currently, internationally recognized first-line treatments mainly include psychological interventions, such as trauma-focused cognitive behavioral therapy, and pharmacological treatment primarily using selective serotonin reuptake inhibitors (SSRIs, such as paroxetine and sertraline). While these methods are effective for some patients, their limitations are significant: psychotherapy requires highly skilled therapists, has a long treatment course, and is limited in accessibility; while drug therapy is often accompanied by a series of intolerable side effects, including but not limited to sexual dysfunction, significant weight gain, emotional blunting, gastrointestinal reactions, and withdrawal syndrome. These problems lead to generally poor patient adherence, and a considerable proportion of patients still do not respond well to existing treatments or have residual symptoms, highlighting the urgent clinical need to develop new treatment strategies.

[0003] In recent years, with the rapid development of neuroscience and molecular biology, the understanding of the pathological mechanisms of PTSD has expanded from the traditional hypothesis of "monoamine neurotransmitter imbalance" to a more complex neurobiological system level, particularly the two key dimensions of abnormal neuroplasticity and systemic inflammatory response. Regarding neuroplasticity, numerous neuroimaging and autopsy studies have consistently found that PTSD patients exhibit reduced volume in key brain structures, decreased density of neuronal dendritic spines, and weakened synaptic connections. The hippocampus, as a core brain region for memory integration and emotion regulation, is considered to have significant implications for traumatic memory fixation, retrieval abnormalities, and flashback symptoms due to impaired synaptic plasticity. Regarding inflammatory mechanisms, studies have found that PTSD patients often have persistently elevated levels of pro-inflammatory cytokines in peripheral blood and the central nervous system, along with dysfunction of the hypothalamus-pituitary-adrenal axis. This chronic low-grade inflammation can not only directly damage neurons but also further exacerbate synaptic plasticity damage and neurotransmitter imbalance by affecting glial cell function, altering blood-brain barrier permeability, and interfering with neurotrophic factor signaling pathways. Furthermore, emerging metabolomics research reveals that PTSD patients have characteristic metabolic spectrum disorders involving multiple pathways such as energy metabolism, lipid metabolism, and amino acid metabolism. These metabolic disorders may be the key link connecting upstream stress response with downstream neuroinflammation and synaptic dysfunction.

[0004] Based on this, the inventors have creatively proposed to correct metabolic abnormalities in PTSD, regulate neurotransmitter synthesis, enhance synaptic plasticity, and reduce inflammation levels by supplementing specific metabolite components, thereby achieving the treatment of PTSD.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The purpose of this invention is to provide a nutrient composition for the prevention and / or treatment of post-traumatic stress disorder, avoiding the side effects of existing drug treatments and improving safety and long-term treatment adherence.

[0007] On one hand, the present invention provides a nutrient composition comprising the following components: α-ketoglutarate, thiamine hydrochloride, L-serine, L-tryptophan and L-tyrosine.

[0008] In some embodiments of the present invention, the nutrient composition comprises the following components in parts by weight: 10-12 parts of α-ketoglutarate, 4-6 parts of thiamine hydrochloride, 7-9 parts of L-serine, 6-8 parts of L-tryptophan, and 5-7 parts of L-tyrosine.

[0009] In some embodiments of the present invention, the nutrient composition comprises the following components in parts by weight: 11 parts α-ketoglutarate, 5 parts thiamine hydrochloride, 8 parts L-serine, 7 parts L-tryptophan, and 6 parts L-tyrosine.

[0010] The nutrient composition of the present invention can be prepared according to various known pharmaceutical or food preparation methods in actual use, wherein the purification and refining of raw materials and the preparation method of the composition can all adopt methods already available in the prior art.

[0011] On the other hand, the present invention provides a medicament comprising the above-described nutrient composition and pharmaceutically acceptable excipients.

[0012] Pharmaceutically acceptable excipients include, but are not limited to, pharmaceutically acceptable carriers, diluents, fillers, binders, disintegrants, lubricants, suspending agents, dispersants, adhesives, sweeteners, flavoring agents, preservatives, antioxidants, colorants, stabilizers, pH adjusters, or other excipients. Therapeutic inert inorganic or organic carriers known to those skilled in the art include, but are not limited to, lactose, corn starch or derivatives thereof, talc, vegetable oils, waxes, fats, polyhydroxy compounds such as polyethylene glycol, water, sucrose, ethanol, glycerin, and the like. Various diluents, fillers, preservatives, lubricants, dispersants, flavoring agents, humectants, antioxidants, sweeteners, colorants, stabilizers, and the like may also be added as needed to aid in the stability of the formulation or to help improve its activity or bioavailability.

[0013] In some embodiments of the present invention, the dosage form of the drug is selected from any one of granules, tablets, capsules, pills, injections, lyophilized powder injections, powders, oral liquids, and syrups.

[0014] In some embodiments of the present invention, the dosage form of the drug is granules, and the pharmaceutically acceptable excipients include fillers, binders, flavoring agents, and fragrances. Preferably, the filler comprises a mixture of sucrose powder and soluble starch, and the binder comprises a 70% ethanol solution.

[0015] In some embodiments of the invention, the dosage form of the drug is a tablet, and the pharmaceutically acceptable excipients include fillers, disintegrants, binders, and lubricants. Preferably, the fillers include microcrystalline cellulose and lactose, the disintegrants include croscarmellose sodium, and the binders include hydroxypropyl methylcellulose.

[0016] Preferably, the unit dose of the nutrient composition in the drug is 350-400 mg, more preferably 370 mg.

[0017] In another aspect, the present invention provides a method for preparing the above-mentioned drug, which includes the following steps: measuring each component of the nutrient composition according to the formula and mixing them evenly, and adding the pharmaceutically acceptable excipients to prepare the drug.

[0018] In some embodiments of the present invention, the dosage form of the drug is granules, and the preparation method of the drug includes the following steps: After measuring and sieving each component of the nutrient composition according to the formula, it is mixed evenly with the filler and the flavoring agent, and then the binder is added and stirred evenly to obtain a soft material. After granulating and drying the obtained soft material, the fragrance is added and mixed evenly to obtain the granules.

[0019] In some embodiments of the present invention, the dosage form of the drug is a tablet, and the preparation method of the drug includes the following steps: After measuring and sieving each component of the nutrient composition according to the formula, it is mixed evenly with the filler and the disintegrant, and the binder solution is added. The mixture is stirred and granulated to obtain uniform granules. After drying the granules, the disintegrant is added and mixed, then the lubricant is added and mixed evenly before compression into tablets to obtain the tablets.

[0020] Preferably, the concentration of the adhesive solution is 5% (w / w).

[0021] Preferably, the disintegrant is added in two portions, with half the amount of the formulation added each time.

[0022] Preferably, the drying temperature is 55-65°C. Preferably, the moisture content of the dried particles is 2%-3%.

[0023] In another aspect, the present invention provides a food product comprising the above-described nutrient composition and food additives. The nutrient composition of the present invention can be prepared into a dietary form more readily accepted by clinical patients, thereby enabling patients to receive earlier intervention through dietary therapy.

[0024] In some embodiments of the present invention, the food is a health food.

[0025] In some embodiments of the present invention, the food is a beverage.

[0026] In another aspect, the present invention provides the use of the above-mentioned nutrient composition, the above-mentioned drug, or the above-mentioned food in the preparation of a drug or food for the prevention and / or treatment of post-traumatic stress disorder.

[0027] Compared with the prior art, the present invention has at least the following beneficial effects: Serum metabolite supplementation effect: The nutrient composition of the present invention does not work by a single component, but by screening five components through metabolomics technology to find changes in the pathophysiological process of PTSD, and then designing five formulation components. Supplementing the five components together is beneficial to improving PTSD.

[0028] Novel Mechanism of Action: This invention is the first to propose treating PTSD by precisely proportioning these five components to supplement metabolism. This is completely different from the mechanism of traditional SSRIs, which inhibit reuptake by a single receptor, and provides a brand-new approach to the treatment of PTSD.

[0029] High safety: The selected components are all endogenous substances or essential nutrients in the human body. When used in reasonable doses, they are expected to have extremely high safety, with side effects far lower than traditional chemically synthesized drugs, which is expected to improve patients' long-term treatment compliance.

[0030] Diverse dosage forms and flexible applications: The nutrient composition of the present invention can be prepared into various pharmaceutically acceptable dosage forms, such as tablets, capsules, granules, oral liquids, etc., to facilitate use by different patient groups. Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the specific embodiments of this disclosure or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this disclosure. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0032] Figure 1 The image shows the total ion current (TIC) chromatograms of serum samples from normal control and model groups detected by UHPLC-OE-MS in positive ion mode.

[0033] Figure 2 The image shows the total ion current (TIC) chromatograms of serum samples from normal control and model groups detected by UHPLC-OE-MS in negative ion mode.

[0034] Figure 3 The relative content differences of five components in the serum of mice in the normal control group and the model group are shown. # indicates that compared with the normal control group, P<0.05.

[0035] Figure 4 The results of the elevated cross maze test for assessing anxiety-like behavior in mice in each experimental group are shown. # indicates that compared with the normal control group, P<0.05; * indicates that compared with the model group, P<0.05.

[0036] Figure 5The results of the open field test assessing anxiety-like behavior in mice of each experimental group are shown, among which... Figure 5 A is the distance from the center of the open field; Figure 5 B represents the time at the center of the open field; Figure 5 C represents the total distance of the open field; Figure 5 D represents the representative trajectory diagram of the open field test. Where # indicates a comparison with the normal control group, P < 0.05; * indicates a comparison with the model group, P < 0.05.

[0037] Figure 6 The results of the fear memory test assessing the extinction of fear memory in mice of each experimental group are shown, in which... Figure 6 A represents the duration of fear stagnation during the resolution phase; Figure 6 B represents the fear stagnation time during re-exposure. Where # indicates a comparison with the normal control group, P < 0.05; * indicates a comparison with the model group, P < 0.05.

[0038] Figure 7 The results of ELISA detection of CORT levels in the serum of mice in each experimental group are shown. # indicates that compared with the normal control group, P<0.05; * indicates that compared with the model group, P<0.05.

[0039] Figure 8 The results of Western blot analysis of hippocampal synaptic proteins and inflammatory proteins in the hippocampal tissue of mice in each experimental group are shown. Figure 8 A represents the synaptic protein band; Figure 8 B represents the quantitative analysis of GluN2A; Figure 8 C represents the quantitative analysis of GluN2B; Figure 8 D represents PSD-95 quantitative analysis; Figure 8 E represents the band of inflammatory proteins; Figure 8 F represents quantitative analysis of NLRP3; Figure 8 G represents quantitative analysis of NF-κB; Figure 8 H represents the quantitative analysis of IL-6. Where # indicates a comparison with the normal control group, P < 0.05; * indicates a comparison with the model group, P < 0.05.

[0040] Figure 9 The results of behavioral and ELISA verification of the efficacy of different drug combinations in Experiment Example 2 are shown, in which... Figure 9 A is the distance from the center of the open field; Figure 9 B represents the time at the center of the open field; Figure 9 C represents the total distance of the open field; Figure 9 D represents the open arm time of the elevated cross maze experiment; Figure 9 E represents the duration of fear stagnation during the resolution phase; Figure 9 F represents the fear stagnation time during the re-exposure period; Figure 9G represents the CORT content in the serum of mice in each experimental group as detected by ELISA. # indicates a comparison with the normal control group, P < 0.05; * indicates a comparison with the model group, P < 0.05. Detailed Implementation

[0041] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of this application. Unless otherwise specified, 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 application pertains.

[0042] It should be noted that the terminology used herein is for the purpose of describing particular implementations only and is not intended to limit the exemplary implementations according to this application. As used herein, the singular form includes the plural form as well as the singular form unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms “comprising” and / or “including” are used herein, they should generally be understood as open-ended and non-limiting, e.g., not excluding other elements or steps not described, unless specifically stated otherwise or understood from the context.

[0043] It should be understood that the order of the steps or the order in which certain actions are performed is not important as long as the invention remains operable. Furthermore, two or more steps or actions can be performed simultaneously.

[0044] Furthermore, the numerical ranges and parameters used to define the present invention are approximate values, and the relevant values ​​in the specific embodiments have been presented as precisely as possible herein. However, any value inevitably contains standard deviations due to individual test methods. Therefore, unless explicitly stated otherwise, it should be understood that all ranges, quantities, values, and percentages used in this disclosure are modified with the word "approximately". In this document, "approximately" generally means an actual value within plus or minus 10%, 5%, 1%, or 0.5% of a particular value or range.

[0045] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0046] Unless otherwise stated, all reagents used in the examples are commercially available or synthesized using conventional methods and are ready for use without further processing, as are the instruments used in the examples.

[0047] Example 1. Screening of effective components Mice were divided into a normal control group and a model group (n=7). The model group used the SPS method to establish a mouse PTSD model. After one week of acclimatization, C57BL6 mice were placed in a restraint device to prevent free movement for 2 hours. After restraint, the mice were briefly rewarmed and then placed in a cylindrical transparent plastic tank (d=24 cm, H=50 cm) for forced swimming for 20 minutes (water temperature 20-24℃). After swimming, the mice rested for 15 minutes until they regained consciousness and behavioral ability. Then, the mice were anesthetized in a sealed container containing 5% isoflurane until unconsciousness. This anesthesia was repeated three times. After anesthesia, once the mice regained consciousness and behavioral ability, they were placed in an electric shock chamber to receive a single electric shock (current intensity 2 mA, duration 2 s). The SPS model was completed after the mice underwent the restraint, forced swimming, anesthesia, and electric shock procedure. All mice were fasted and deprived of water during the modeling period.

[0048] Fourteen days later, the mice in both groups were anesthetized with 5% isoflurane gas, and blood was collected by decapitation immediately after anesthesia. The blood was placed in centrifuge tubes and left at room temperature for 2 hours, then centrifuged at 3000 rpm / min for 15 minutes at 4°C. The supernatant was then slowly collected and placed in clean centrifuge tubes.

[0049] Transfer 100 μL of serum sample to an EP tube, add 400 μL of extraction buffer (methanol:acetonitrile = 1:1 (V / V)), the extraction buffer contains an isotope-labeled internal standard; vortex for 30 s, sonicate for 10 min (ice-water bath); incubate at -40℃ for 1 h; centrifuge the sample at 4℃, 12000 rpm (centrifugal force 13800 (×g), radius 8.6 cm) for 15 min; collect the supernatant in a sample vial for instrumental analysis; mix equal amounts of supernatant from all samples to form a QC sample for instrumental analysis.

[0050] Polar metabolites were detected using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-OE-MS). This project employed a Vanquish (Thermo Fisher Scientific) UHPLC system, using a Waters ACQUITY UPLC BEH Amide (2.1 mm × 50 mm, 1.7 μm) column for chromatographic separation of target compounds. Phase A of the HPLC was aqueous, containing 25 mmol / L ammonium acetate and 25 mmol / L ammonia; Phase B was acetonitrile. Sample tray temperature: 4 ℃; injection volume: 2 μL. The Orbitrap Exploris 120 mass spectrometer was able to acquire primary and secondary mass spectrometry data under the control of software (Xcalibur, version 4.4, Thermo). Detailed parameters are as follows: Sheath flow velocity: 50 Arb Auxiliary airflow velocity: 15 Arb Capillary temperature: 320℃ Full scan resolution: 60000 MS / MS resolution: 15000 Collision Energy: SNCE 20 / 30 / 40 Spray voltage: 3.8 kV (positive ion mode) or -3.4 kV (negative ion mode).

[0051] Test results as follows Figure 1 and Figure 2 As shown, the raw data were converted to mzXML format using ProteoWizard software, and then metabolites were identified. Data analysis revealed significant differences in the serum levels of α-ketoglutarate, thiamine hydrochloride, L-serine, L-tryptophan, and L-tyrosine between the normal control group and the model group. Figure 3 Thus, a nutrient composition containing the above five components was designed.

[0052] Example 2. Preparation of the composition granules The formulation of the granules in this embodiment is as follows: Active components: 110 g α-ketoglutarate, 50 g thiamine hydrochloride, 80 g L-serine, 70 g L-tryptophan, 60 g L-tyrosine.

[0053] Pharmaceutical excipients: Filler / carrier: 300 g of a mixture of sucrose powder and soluble starch (1:1); Adhesive: 70% (v / v) ethanol solution, appropriate amount; Flavoring agent: Stevioside 5 g; Flavoring: 3 g of orange flavoring.

[0054] The five active ingredients were each passed through an 80-mesh sieve and then placed together with sucrose powder, soluble starch, flavoring agents, and other excipients in a trough mixer and thoroughly mixed to obtain a dry powder mixture. A 70% ethanol solution was slowly added to the uniformly mixed dry powder mixture while stirring, to create a suitable soft material that "can be formed into a ball when squeezed but crumbles easily when pressed." The obtained soft material was then extruded through a 14-mesh sieve to granulate, obtaining wet granules. The wet granules were placed in a fluidized bed dryer or a hot air circulating oven and dried at 60-65°C to control the granule moisture content between 2% and 3%. The dried granules were then passed through a 14-mesh sieve again to break up any clumps. The granulated dry granules were mixed with orange flavoring and placed in a three-dimensional motion mixer for uniform mixing. An automatic granule packaging machine was used to package the uniformly mixed granules into aluminum-plastic composite film bags, each containing approximately 370 mg of active ingredients, thus obtaining the granules of this embodiment.

[0055] Example 3. Preparation of the composition tablet The formulation of the tablet composition in this embodiment is as follows: Active components: 110 g α-ketoglutarate, 50 g thiamine hydrochloride, 80 g L-serine, 70 g L-tryptophan, 60 g L-tyrosine.

[0056] Pharmaceutical excipients: Filler: 80 g each of microcrystalline cellulose and lactose; Disintegrant: 15 g of croscarmellose sodium cellulose; Adhesive: 5 g of hydroxypropyl methylcellulose; Lubricant: 4.5 g magnesium stearate.

[0057] Slowly add 5 g of hydroxypropyl methylcellulose (HPMC) to an appropriate amount of purified water, stirring until completely dissolved to prepare a 5% (w / w) binder solution. Mix the active ingredient, filler, and 7.5 g of disintegrant powder together for 30 minutes, then transfer the uniformly mixed powder to a granulator. While stirring, slowly add the prepared 5% HPMC aqueous solution as a binder, controlling the addition rate and amount to form a soft material that "clumps together when grasped but crumbles upon contact." The entire process requires approximately 300-400 mL of binder solution. After stopping the addition, continue stirring and granulating for 1-2 minutes to ensure uniform particle growth. Quickly transfer the resulting wet granules to a hot air circulating oven, spreading the granules to a thickness not exceeding 2 cm, and dry at 60℃±5℃ until the moisture content of the granules is below 3.0%. Finally, pass the dried granules through a gyratory granulator using a 20-mesh stainless steel sieve to ensure uniform particle size. Transfer the granulated granules to a mixer, add 7.5 g of disintegrant, and mix for 10 minutes. Add the prescribed amount of magnesium stearate and continue mixing for 5 minutes to ensure thorough and uniform mixing. Send the mixed granules to a tableting machine to produce tablets containing approximately 370 mg of the active ingredient per tablet.

[0058] Comparative Example. Preparation of Comparative Composition Granules Granules of the comparative composition were prepared according to the formulation and method of Example 2, except that L-serine in the formulation of Example 2 was replaced with an equal amount of L-leucine, while the other components, contents and preparation methods remained unchanged.

[0059] To demonstrate the effectiveness of this invention, the following animal experiments were conducted.

[0060] Experimental Example 1. Pharmacological Efficacy Experiment Model Establishment: A mouse PTSD model was established using the SPS method. C57BL6 mice were acclimatized to their environment for one week, then restrained in a restraint device for 2 hours. After restraint, the mice were briefly rewarmed and then placed in a cylindrical transparent plastic tub (d=24 cm, H=50 cm) for forced swimming for 20 minutes (water temperature 20-24℃). After swimming, the mice rested for 15 minutes until they regained consciousness and behavioral ability. Then, they were anesthetized in a sealed container containing 5% isoflurane until unconsciousness. This anesthesia was repeated three times. After anesthesia, once consciousness and behavioral ability were restored, the mice were placed in an electric shock chamber to receive a single electric shock (2 mA, 2 s). The SPS model was completed after the mice underwent restraint, forced swimming, anesthesia, and electric shock procedures. All mice were fasted and deprived of water during the modeling period.

[0061] Grouping and Administration: C57BL6 mice were randomly divided into 6 groups: normal control group (normal mice, given saline), model group (PTSD model mice, given saline), model + positive drug group (PTSD model mice, given paroxetine hydrochloride, 10 mg / kg / day), model + low-dose group (PTSD model mice, given granules of the composition of Example 2 of this invention, 370 mg / kg / day based on the active ingredient), model + medium-dose group (PTSD model mice, given granules of the composition of Example 2 of this invention, 740 mg / kg / day based on the active ingredient), and model + high-dose group (PTSD model mice, given granules of the composition of Example 2 of this invention, 1480 mg / kg / day based on the active ingredient). Each group was administered the drug by gavage for 14 consecutive days.

[0062] Behavioral testing: (1) The elevated plus maze (EPM) test was used to assess anxiety-like behavior in SPS mice. Behavioral information was recorded using an automated behavioral analysis system, and the time mice spent in the open arm was statistically analyzed. Shorter time spent in the open arm indicated more pronounced anxiety-like behavior. Results showed that, compared to the normal control group, the model group spent less time in the open arm. Administration of medium and high doses of granules, similar to the positive control drug paroxetine hydrochloride, increased the exploration time of model mice in the open arm. Figure 4 ).

[0063] (2) The open field test (OFT) was used to assess anxiety-like behavior in SPS mice. Central distance, central time, and total distance were collected using an automated behavioral analysis system. The shorter the distance and time spent in the central region, the more severe the anxiety-like behavior. Results showed that compared to the normal control group, the model group had reduced central time and central distance in the open field. Low, medium, and high doses of the granules combined with the positive control drug paroxetine hydrochloride increased the central distance in the open field of the model mice, while medium and high doses of the granules combined with the positive control drug paroxetine hydrochloride increased the central time in the open field. There was no difference in total distance among the groups, indicating that the composition did not affect the motor function of the mice. Figure 5 ).

[0064] (3) Fear memory test (FMT) was used to evaluate the extinction of fear memory in SPS mice. The fear memory extinction experiment was divided into four phases: adaptation, training, re-exposure, and extinction, with each phase spaced 24 hours apart. During the re-exposure phase, the freezing time of each mouse was recorded in segments (every 3 minutes). During the extinction phase, the freezing time of the mice in the first 3 minutes was recorded. The results showed that compared with the normal control group, the freezing time of fear in the model group was increased, while the administration of low, medium, and high doses of granules and the positive control drug paroxetine hydrochloride reduced the freezing time of fear in the model mice. The 3-minute segmented statistics also showed that the freezing time of fear in the model group was increased, while the administration of medium and high doses of granules and the positive control drug paroxetine hydrochloride reduced the freezing time of fear in the model mice. Figure 6 ).

[0065] Biochemical indicator testing: After the experiment, mouse serum and hippocampal tissue were collected. The level of corticosterone (CORT) in the serum was detected by ELISA, and the hippocampal GluN2A, GluN2B, and PSD-95 synaptic proteins, as well as NLRP3, NF-κB, and IL-6 inflammatory proteins, were detected by Western blot.

[0066] ELISA analysis revealed increased CORT levels in the serum of the model group, while administration of low, medium, and high doses of the granules significantly reduced CORT levels in the model mice. Figure 7 ).

[0067] Western blot analysis revealed that, compared with normal control mice, the hippocampus of model mice showed decreased levels of GluN2A and PSD-95, and increased levels of GluN2B, NLRP3, NF-κB, and IL-6 proteins. Administration of medium and high doses of the granules significantly reversed these changes in the hippocampus of model mice. Figure 8).

[0068] Conclusion: The above experimental results show that the composition of the present invention can effectively improve anxiety-like behavior and promote the extinction of fear memory in PTSD model mice. Its mechanism of action may be related to regulating COTR level, enhancing synaptic plasticity, and reducing inflammatory response.

[0069] Experimental Example 2. Comparative Experiment of Drug Efficacy Following the method in Experiment Example 1, a mouse PTSD model was established using the SPS method.

[0070] Grouping and Administration: C57BL6 mice were randomly divided into four groups: normal control group (normal mice, given saline), model group (PTSD model mice, given saline), model + combination 1 group (PTSD model mice, given the granules of the composition of Example 2 of this invention, at 740 mg / kg / day based on the active ingredient), and model + combination 2 group (PTSD model mice, given the granules of the comparative composition of the control group, at 740 mg / kg / day based on the active ingredient). Each group was administered the medication by gavage for 14 consecutive days.

[0071] At the end of the experiment, the effects of different compositions on mice were detected using the behavioral methods described in Experiment Example 1, and the CORT content in the serum of mice in each group was detected using the ELISA method in the biochemical index detection.

[0072] Open field experiments revealed that, compared to the normal control group, the model group experienced reduced center time and center distance in the open field. Administration of the granules of the composition from Example 2 increased the center distance and center time in the open field for the model mice, but administration of the control composition granules showed no statistically significant difference. There was no difference in total distance among the groups, indicating that the composition did not affect the motor function of the mice. Figure 9 AC).

[0073] The elevated cross maze test results showed that, compared with the normal control group, the model group had a shorter exploration time in the open arm. Administration of the granules of the composition from Example 2 increased the exploration time of the model mice in the open arm, but administration of the control composition granules showed no statistically significant difference. Figure 9 D).

[0074] Fear memory tests revealed that, compared to the normal control group, the fear lapse time in the model group was increased, while administration of the granules of the composition from Example 2 reduced the fear lapse time in the model mice. The 3-minute segmented statistical analysis also showed an increased fear lapse time in the model group, while administration of the granules of the control composition reduced the fear lapse time in the model mice. However, there was no statistically significant difference in fear lapse time or 3-minute segmented fear lapse time between the mice administered the control composition granules. Figure 9 EF).

[0075] After the experiment, mouse serum was collected, and the level of corticosterone (CORT) in the serum was detected by ELISA. ELISA showed that compared with the normal control group, the level of CORT in the model group serum was increased, while administration of the granules of the composition in Example 2 significantly reduced the level of CORT in the model mice. However, administration of the granules of the control composition showed no statistically significant difference. Figure 9 G).

[0076] Conclusion: The above experimental results show that replacing the composition of the present invention weakens the improvement effect on anxiety-like behavior and fear memory extinction in PTSD model mice, and has no significant difference in the effect on reducing serum COTR levels.

[0077] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A nutrient composition, characterized in that, The nutrient composition comprises the following components: α-ketoglutarate, thiamine hydrochloride, L-serine, L-tryptophan, and L-tyrosine.

2. The nutrient composition according to claim 1, characterized in that, The nutrient composition comprises the following components in parts by weight: 10-12 parts α-ketoglutarate, 4-6 parts thiamine hydrochloride, 7-9 parts L-serine, 6-8 parts L-tryptophan, and 5-7 parts L-tyrosine.

3. The nutrient composition according to claim 1, characterized in that, The nutrient composition comprises the following components in parts by weight: 11 parts α-ketoglutarate, 5 parts thiamine hydrochloride, 8 parts L-serine, 7 parts L-tryptophan, and 6 parts L-tyrosine.

4. A drug, characterized in that, The drug comprises the nutrient composition according to any one of claims 1-3 and pharmaceutically acceptable excipients.

5. The drug according to claim 4, characterized in that, The dosage form of the drug is selected from any one of granules, tablets, pills, capsules, injections, lyophilized powder injections, powders, oral liquids, and syrups.

6. The drug according to claim 4, characterized in that, The drug is in the form of granules, and the pharmaceutically acceptable excipients include fillers, binders, flavoring agents, and fragrances.

7. The drug according to claim 4, characterized in that, The drug is in tablet form, and the pharmaceutically acceptable excipients include fillers, disintegrants, binders, and lubricants.

8. The method for preparing the drug according to claim 4, characterized in that, The process includes the following steps: measuring each component of the nutrient composition according to the formula and mixing them evenly, and adding the pharmaceutically acceptable excipients to prepare the drug.

9. A food product, characterized in that, The food includes the nutrient composition according to any one of claims 1-3 and food additives.

10. The use of the nutrient composition according to any one of claims 1-3, the drug according to any one of claims 4-7, or the food according to claim 9 in the preparation of a drug or food for the prevention and / or treatment of post-traumatic stress disorder.

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