Serine and l-lysine salt and synthesis method and application thereof

Abstract

The application discloses serine and L-lysine salt as shown in formula I or formula II and a preparation method and application thereof in the nervous system disease autism spectrum disorder. The synthesized serine and L-lysine salt has lower heavy metal content and higher stability compared with serine or lysine, and overcomes the problems of high heavy metal content and storage instability when the two amino acids are used alone. The serine and L-lysine salt can obviously reduce the expression of NICD and Hes1 proteins, and indicates that the two serine and L-lysine salts can effectively inhibit the abnormal activation of the Notch signal pathway.

Description

Technical Field

[0001] This application relates to the field of organic synthesis technology, and more specifically, to a method for the formation of a salt from serine and L-lysine, its synthesis process, and its application. Background Technology

[0002] Autism spectrum disorder (ASD) is a neurodevelopmental disorder primarily characterized by social dysfunction and repetitive, stereotyped behaviors. While cognitive impairment is not a typical symptom of autism, it is prevalent in most patients and is often accompanied by impaired learning and memory abilities. Current research shows that the neurobiological mechanisms of autism are complex, with the Notch signaling pathway acting as a key regulator in development, involved in neuronal proliferation, differentiation, and synapse formation. The intracellular domain of the Notch receptor (NICD) is released via γ-secretase-mediated cleavage, entering the nucleus to regulate downstream gene transcription, such as Hes family genes, thereby affecting neurodevelopment and function. Presenilin (PSEN), a core component of the γ-secretase complex, mediates Notch receptor activation, releasing NICD. Abnormal Notch signaling activation, initiating downstream gene expression in the nucleus, has been shown to be associated with neurodevelopmental abnormalities. Using a valproic acid (VPA)-induced autism rat model, studies have revealed abnormal neuronal proliferation in the hippocampus, impaired spatial learning and memory, providing an experimental basis for exploring the regulation of Notch signaling in autism. The Notch signaling pathway, as an important signaling pathway for cell fate regulation, may be involved in the development and progression of autism.

[0003] Serine is a non-essential amino acid that participates in various physiological processes, playing a crucial role, especially in maintaining the function of the central nervous system. Serine is not only a precursor to phospholipid synthesis and participates in the formation of cell membranes and myelin proteins, but it is also closely related to the function of RNA and DNA. As the protective layer of nerve fibers, the integrity of the myelin sheath depends on an adequate supply of serine; a lack of serine can lead to myelin damage, decreased information transmission efficiency, and neurological dysfunction.

[0004] Lysine is an essential amino acid that regulates fatty acid metabolism and promotes energy supply by participating in the synthesis of carnitine. At the same time, lysine promotes the secretion of pepsin and gastric acid, improving calcium absorption and bone growth. Lysine deficiency can lead to anorexia, nutritional anemia, and neurodevelopmental disorders.

[0005] Studies have shown that autistic patients have enlarged hippocampal volumes, accompanied by impaired spatial learning and memory abilities. As a crucial brain region for learning and memory, abnormal development of the hippocampus is closely related to autism. The Notch signaling pathway plays a key role in neuronal differentiation, proliferation, and synapse formation. VPA-induced autism animal models exhibit excessive hippocampal neuronal proliferation and cognitive deficits, suggesting that abnormal activation of Notch signaling may be involved in this pathological process. Summary of the Invention

[0006] Based on the neuroprotective and metabolic regulatory functions of serine and lysine, this invention discovers that the salt formation of serine and lysine can improve the abnormal proliferation of hippocampal neurons and restore spatial learning and memory abilities by regulating the Notch1 / Hes1 signaling pathway, thereby realizing its application in the aforementioned neurological disease, autism spectrum disorder. In addition, compared with serine or lysine alone, the salt formation of serine and lysine is more stable and has higher bioavailability.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A serine and L-lysine salt having a structure as shown in Formula I or Formula II: .

[0008] The crystals of serine and lysine salts described in Formula I have X-ray powder diffraction patterns using Cu ka radiation with diffraction peaks at the following 2θ angles: 18.444±0.2°, 19.006±0.2°, 22.837±0.2°, 28.272±0.2°, and 30.265±0.2°.

[0009] Preferably, its X-ray powder diffraction pattern using Cu ka radiation has diffraction peaks at the following 2θ angles: 9.985±0.2°, 18.444±0.2°, 19.006±0.2°, 20.631±0.2°, 22.837±0.2°, 28.272±0.2°, 30.265±0.2°, 32.869±0.2°, 33.257±0.2°, and 34.943±0.2°.

[0010] Further preferably, the X-ray powder diffraction pattern of the serine and lysine salt crystals of Formula I using Cu ka radiation is as follows: Figure 5 As shown.

[0011] The crystals of serine and lysine salts described in Formula II have diffraction peaks at the following 2θ angles in their X-ray powder diffraction patterns using Cu ka radiation: 19.997±0.2°, 22.827±0.2°, 23.083±0.2°, 27.145±0.2°, and 30.754±0.2°.

[0012] Preferably, the crystals of serine and lysine salts according to Formula II have diffraction peaks at the following 2θ angles in their X-ray powder diffraction patterns using Cu ka radiation: 6.818±0.2°, 18.658±0.2°, 19.997±0.2°, 20.794±0.2°, 22.051±0.2°, 22.827±0.2°, 23.083±0.2°, 28.477±0.2°, 30.754±0.2°, 33.510±0.2°, and 35.188±0.2°. More preferably, the X-ray powder diffraction patterns of the serine and lysine salts according to Formula II using Cu ka radiation are as follows: Figure 6 As shown.

[0013] The synthesis of serine and lysine salts according to Formula I includes the following steps:

[0014] L-serine and L-lysine were dissolved in water, heated until dissolved, and then acetone was added dropwise to obtain product I.

[0015] The synthesis of serine and lysine salts according to Formula II includes the following steps:

[0016] D-serine and L-lysine were dissolved in water, heated until dissolved, and then acetone was added dropwise to obtain product II.

[0017] The present invention also provides the use of the aforementioned serine and L-lysine salts in medicaments for the prevention, treatment or improvement of nervous system diseases.

[0018] Furthermore, the neurological disorder in question is autism spectrum disorder.

[0019] Beneficial effects: 1. The serine synthesized in this invention forms a salt with L-lysine, which has a lower heavy metal content and higher stability compared to serine or lysine alone. This overcomes the problems of high heavy metal content and unstable storage when the two amino acids are used alone, thus creating conditions for clinical application.

[0020] 2. Compared with the VPA group, in the treated rat model, the expression of NICD and Hes1 proteins in the serine and L-lysine salt-forming groups (VPA+I group, VPA+II group) was significantly lower than that in the single-component amino acid groups (VPA+L,S, VPA+D,S, VPA+L,L) (p < 0.05). Moreover, the expression of NICD and Hes1 proteins in the salt-forming groups was significantly lower than that in the single-component treatment groups, and the difference was statistically significant, indicating that both treatments can effectively inhibit the abnormal activation of the Notch signaling pathway. Attached Figure Description

[0021] Figure 1 This is the 1H NMR spectrum of the salt formation (I) of L-serine and L-lysine as analyzed by Bruke NMR.

[0022] Figure 2 This is the 1H NMR spectrum of the salt formation (II) of D-serine and L-lysine analyzed by Bruke NMR.

[0023] Figure 3 This is the infrared spectrum of the salt formation (I) of L-serine and L-lysine.

[0024] Figure 4 It is the infrared spectrum of the salt formation (II) of D-serine and L-lysine.

[0025] Figure 5 This is an X-ray powder diffraction pattern of L-serine and L-lysine salt (I) crystals.

[0026] Figure 6 This is an X-ray powder diffraction pattern of the D-serine and L-lysine salt (II) crystals.

[0027] Figure 7 The expression of Hes1 and NICD in HC of 12 groups of rats.

[0028] Figure 8 This is a statistical result of the degree of neuronal degeneration in the cerebral cortex of mice after drug treatment and related histograms. Detailed Implementation

[0029] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present application, and not all embodiments.

[0030] The L-serine used in the embodiments of this invention was purchased from Wonsung P&C Co., Ltd. of South Korea, batch number LSA-P25030001.

[0031] The D-serine used in the embodiments of this invention was purchased from Wonsung P&C Co., Ltd. of South Korea, batch number DSA-P25030002.

[0032] The L-lysine used in the embodiments of this invention was purchased from Shanghai Yuanye Biotechnology Co., Ltd., batch number S20049-100g.

[0033] Example 1: Preparation of Compound I

[0034] In a 200 mL single-necked flask under nitrogen protection, 10.5 g of L-serine, 20 g of distilled water, and 14.6 g of L-lysine were added. The mixture was slowly stirred while the temperature was raised to 60 °C. Then, 10 g of bagged polishing resin was added and stirred for 2 hours. The resin was then removed, and the mixture was cooled to 20-25 °C. Simultaneously, 100 mL of acetone was added dropwise. The mixture was stirred at room temperature for 12 hours, filtered, and then vacuum dried at 60 °C for 12 hours to obtain 1.35 g of solid compound I2, with a yield of 85%. The detection parameters were as follows: 1H NMR (D2O, 400MHz): δ3.87-3.72(m, 4H), 3.59-3.54 (S, 2H), 3.52-3.47 (m, 1H), 2.96-2.86(m, 3H), 1.73-1.55(m, 6H), 1.45-1.24 (m, 3H); LC-MS (ESI+APCI) Calcd for C6H 14 N2O2(Lysine):146.19,found [M-1] - 145;LC-MS(ESI+APCI) Calcd for C3H7NO3(Serine):105.09,found [M-1] - 104. IR(neat) v=2922.3, 2146.4, 1573.0, 1509.0, 1467.4, 1403.5, 1331.3,1124.5, 1083.4, 1036.0, 1010.7, 966.2, 917.0, 848.5, 803.2, 661.4, 607.6,498.3. The XRPD diffraction characteristic peaks of the serine and lysine salts of compound I are shown in Table 1 and... Figure 5 As shown.

[0035] Table 1. XRPD diffraction characteristic peaks of crystals containing serine and lysine salts of compound I.

[0036] Example 2 is a preparation example of compound II. In a 200 mL single-necked flask under nitrogen protection, 10.5 g of D-serine, 20 g of distilled water, and 14.6 g of L-lysine were added. The mixture was slowly stirred while the temperature was raised to 60 °C. Then, 10 g of bagged polishing resin was added and stirred for 2 hours. The resin was then removed, and the mixture was cooled to 20-25 °C. Simultaneously, 100 mL of acetone was added dropwise. The mixture was stirred at room temperature for 12 hours, filtered, and then vacuum dried at 60 °C for 12 hours to obtain 20.80 g of product, with a yield of 83%. The detection parameters were as follows: 1H NMR (D2O, 400MHz): δ3.84-3.68(m, 3H), 3.54-3.37 (m, 3H), 2.94-2.85(m, 3H), 1.74-1.56(m, 6H), 1.44-1.22 (m, 3H). LC-MS (ESI+APCI) Calcd for C6H 14 N2O2(Lysine):146.19,found [M-1] + 147;LC-MS(ESI+APCI) Calcd for C3H7NO3:105.09(Serine),found [M-1] + 106. IR(neat) v= 2925.5, 2073.9, 1577.2, 1515.6, 1405.1, 1347.0, 1259.2,1195.6, 1164.6, 1094.2, 1040.8, 1016.1, 988.1, 951.8, 910.4, 850.5, 803.7,783.9, 723.7, 684.2, 604.2, 557.7, 534.4, 420.7. The XRPD diffraction characteristic peaks of compound II are shown in Table 2 and Figure 6 As shown.

[0037] Table II shows the XRPD diffraction characteristic peaks of the serine and lysine salt crystals described in Formula II.

[0038] Example 3 Stability Measurement One gram of each of L-serine, D-serine, L-lysine, L-serine L-lysine salt (I), and D-serine L-lysine salt (II) was weighed and placed in a 10 ml transparent glass bottle. The contents were measured in a stability test chamber at 60% humidity and 45℃ for 30 days. The results are shown in Table 3. Table 3 Stability

[0039] As shown in Table 3, after 30 days of accelerated testing, the contents of L-serine, D-serine, and L-lysine decreased by 2.82%, 2.90%, and 3.03%, respectively. However, the contents of L-serine and L-lysine in compound (I) decreased by 0.61% and 0.56%, respectively, while the contents of D-serine and L-lysine in compound (II) decreased by 0.51% and 0.47%, respectively. Therefore, the stability of both serine and L-lysine salts was improved.

[0040] Example 4: Detection of heavy metals: I. Sample Pretreatment 1. The microwave digestion steps are as follows: Weigh 0.1–0.3 g of sample (containing L-serine, D-serine, L-lysine, L-serine-L-lysine salt (I) prepared in Example 1, and D-serine-L-lysine salt (II) prepared in Example 2) into a microwave digestion vessel and add 5 mL of 65%–68% nitric acid. Seal the digestion vessel and place it in a microwave digester. Heat according to the following program (using CEM MARS as an example): Incubate at 120℃ for 5 minutes (pre-decomposition of organic matter); at 150℃ for 10 minutes (further digestion); at 180℃ for 15 minutes (complete decomposition). After cooling to room temperature, open the vessel and transfer the digestion solution to a 50 mL PTFE volumetric flask. Dilute to the mark with ultrapure water (resistivity ≥18.2 MΩ·cm), mix well, and filter through a 0.45 μm microporous membrane. Note: The digestion vessel should be rinsed three times with ultrapure water, and the washings should be combined with the rinse water in the volumetric flask to minimize loss.

[0041] II. Conditions and Analysis Process 1. Instrument Configuration ICP-MS host (Thermo iCAP RQ); Microwave digestion system (CEM MARS 6); Ultrapure water system (resistivity ≥ 18.2 MΩ·cm); High-purity argon gas (purity ≥ 99.999%).

[0042] Ion chromatography conditions Chromatographic column: Anion exchange column (such as Dionex IonPac AG7 / AS7) or cation exchange column (such as CS12A) can be selected, depending on the form in which lead exists (Pb²⁺ is usually separated using a cation exchange column).

[0043] Mobile phase: usually dilute nitric acid (0.5-2 mmol / L) or methanesulfonic acid (MSA) solution, adjusted to pH 2-4 to stabilize lead ion form and avoid precipitation.

[0044] Flow rate: 0.5-1.0 mL / min, balancing separation efficiency and analysis time.

[0045] Injection volume: 10-50 μL.

[0046] 2. ICP-MS conditions RF power: 1200-1500 W, ensuring plasma stability.

[0047] Carrier gas flow rate: Argon, typically 0.8-1.2 L / min, to maintain plasma stability.

[0048] Sampling cone / truncation cone: Nickel cone or platinum cone, cleaned regularly to prevent lead deposition.

[0049] Mass number selection: Prioritize the major Pb isotope m / z=208 (highest abundance, 100%), and avoid interference from polyatomic ions (e.g., ²). 08 Pb may be affected by ArO⁺, which can be eliminated through collision / reaction pool technology.

[0050] Collision / Reaction Pool Mode: If interference exists, enable the collision pool (such as He mode) or reaction pool (such as H2 mode) to remove interfering ions.

[0051] 3. Internal standard method for correcting matrix interference The matrix of L-serine, D-serine, L-lysine, L-serine L-lysine (I), and D-serine L-lysine (II) may introduce interference. Elemental correction using 50 μg / L indium (In, m / z=115) as an internal standard was performed before final volume adjustment of the digestion solution. 4. Preparation of Standard Curve Stock solution: Purchase standard solutions (such as Pb and Cd single-element standards, 1000 mg / L) from the National Standard Material Center of Nanjing Wanqing Chemical Glass Instrument Co., Ltd.

[0052] Working solution: Dilute the stock solution stepwise with ultrapure water to prepare a series of standard solutions of different concentrations (e.g., Pb: 0, 0.5, 1, 2, 5, 10 μg / L; Cd: 0, 0.05, 0.1, 0.2, 0.5, 1 μg / L).

[0053] 5. Sample Determination Take an appropriate amount of digestion solution (e.g., 1 mL) into the injection tube, introduce it into the ICP-MS through a peristaltic pump, and record the signal intensity of each element (cps, counts per second).

[0054] Simultaneously measure the working solution curve and blank sample (do not add sample to digestion vessel, only add 5 mL of 65%~68% nitric acid, digestion process is the same as sample).

[0055] III. Data Processing and Result Calculation Plot a standard curve: Plot the standard solution concentration on the x-axis and the signal intensity (after subtracting the blank) on the y-axis, and fit a linear equation.

[0056] Calculate the sample concentration: Substitute the sample signal intensity into the standard curve equation to obtain the heavy metal concentration in the digestion solution.

[0057]

[0058] Where k is the slope of the standard curve and I is the fluorescence signal intensity, the heavy metal concentrations are shown in Table 4: Table 4

[0059] As shown in Table 4, the heavy metal contents of L-serine, D-serine and L-lysine were 15 ppm, 14 ppm and 15 ppm respectively, while compounds (I) and (II) had only 1 ppm and 2 ppm respectively, indicating a significant reduction in heavy metal content.

[0060] Example 5: Establishment of an autistic rat model and efficacy testing Seventy-two Wistar rats (48 females and 24 males) were purchased from a laboratory animal center and acclimatized for one week under periodic light (7:00 AM to 7:00 PM), constant temperature of 25°C, and relative humidity of 55%. The female-to-male ratio was 2:1, and the vaginal plug was examined the following morning to determine embryonic day 1 (E1). Pregnant females were housed separately and randomly divided into two groups: a model group (n=24) received an intraperitoneal injection of sodium valproic acid (VPA, 600 mg / kg) on ​​gestation day 12.5 (E12.5), while the control group (n=24) received an equal volume of normal saline (NS) intraperitoneally. Pups were weaned on postnatal day 23 (PND23). Forty-eight pregnant female mice were randomly divided into two groups. One group of 24 pregnant mice received an intraperitoneal injection of 600 mg / kg valproic acid (VPA) at day 12.5 (the model group), while the other group of 24 pregnant mice received an equal volume of normal saline (NS) (the control group). Pups were weaned at postnatal day (PND). One healthy mouse from each mother's offspring was selected as the experimental subject. Offspring of the model group mothers were randomly divided into six groups (n=4 per group). Group 1 offspring received intraperitoneal injection of I (300 mg / kg) once daily for 2 weeks, designated as VPA+I group. Group 2 received injection of II (300 mg / kg) once daily for 2 weeks, designated as VPA+II group. Group 3 received injection of L-serine (300 mg / kg) once daily for 2 weeks, designated as VPA+L,S group. Group 4 received injection of D-serine (300 mg / kg) once daily for 2 weeks, designated as VPA+D,S group. Group 5 received injection of L-lysine (300 mg / kg) once daily for 2 weeks, designated as VPA+L,L group. Offspring of Group 6 received the same amount of NS, designated as VPA group. Offspring of the control group mothers were randomly divided into six groups (n=4 per group). Group 1 was injected with normal saline (NS) and designated as the Control Group; Group 2 was injected with aminophylline (I) (300 mg / kg) and designated as Group I; Group 3 was injected with aminophylline (II) (300 mg / kg) and designated as Group II; Group 4 was injected with L-serine (300 mg / kg) and designated as Group L,S; Group 5 was injected with D-serine (300 mg / kg) and designated as Group D,S; and Group 6 was injected with L-lysine (300 mg / kg) and designated as Group L,L.

[0061] Twelve groups of male offspring mice were used for subsequent behavioral and molecular testing. The control group consisted of 4 mice; the VPA group consisted of 4 mice; the I group consisted of 4 mice; the II group consisted of 4 mice; the L and S groups consisted of 4 mice; the D and S groups consisted of 4 mice; the L and L groups consisted of 4 mice; the VPA+I group consisted of 4 mice; the VPA+II group consisted of 4 mice; the VPA+L and S groups consisted of 4 mice; the VPA+D and S groups consisted of 4 mice; and the VPA+L and L groups consisted of 4 mice.

[0062] Western blotting was used to detect the expression of NICD and Hes1 in rats from each group. Rats were sacrificed, and their whole brains were quickly removed, with hippocampal tissue isolated. Total protein was extracted using protein lysis buffer, and protein concentration was quantified using the BCA method. Protein samples were placed in 5× loading buffer and denatured at 100°C for 3 minutes. An equal volume of protein (approximately 30 µg) was loaded onto a 12% SDS-PAGE gel, and after electrophoresis to separate the proteins, it was transferred to a PVDF membrane. The membrane was blocked in TBST buffer containing 5% skim milk powder and incubated on a shaker at room temperature for 2 hours. Subsequently, primary antibodies (NICD, Hes1, and internal control GAPDH) were added and incubated overnight at 4°C. The next day, secondary antibodies were incubated at room temperature for 2 hours, and color development was performed using ECL luminescence reagent. ImageJ software was used to analyze the grayscale of the protein bands and calculate the relative expression levels of the target protein and GAPDH.

[0063] Immunofluorescence staining was used to detect Hes1 expression. Frozen brain sections were removed from a -80°C freezer, allowed to thaw naturally, and then permeabilized with 3% Triton X-100 membrane. Antigen retrieval was then performed using a citrate-buffered antigen retrieval kit. The sections were washed three times with PBS for 5 minutes each time. They were then blocked in goat serum for 1 hour. Rabbit anti-Hes1 antibody was added, and the sections were incubated overnight at 4°C. The next day, Alexa Fluor 488-labeled goat anti-rabbit secondary antibody was added, and the sections were incubated at room temperature for 1 hour. Finally, the sections were mounted with anti-fluorescence quenching mounting medium, observed and photographed using a fluorescence microscope, and Hes1 expression was quantitatively analyzed. Results are as follows: Figure 3 As shown: After deep anesthetizing rats, the rats' hearts were perfused with PBS and 4% paraformaldehyde. The entire brain tissue was rapidly separated and obtained, followed by sucrose gradient dehydration, OCT embedding, and frozen sectioning to obtain rat brain sections. The frozen sections were stained with Nissl stain and then observed using a Nikon laser confocal microscope. The results are as follows: Figure 7 As shown: Western blot analysis showed that the expression levels of NICD and Hes1 proteins in the hippocampus of rats in the VPA model group were significantly higher than those in the control group (p < 0.05), suggesting enhanced activation of the Notch signaling pathway in the VPA-induced autism model. Compared with the VPA group, rats treated with serine and L-lysine salts (VPA+I group, VPA+II group) and single components (VPA+L,S, VPA+D,S, VPA+L,L) showed significantly decreased NICD and Hes1 protein expression (p < 0.05), and the decrease was more significant in the salt-forming groups compared to the single-component treatment groups, with statistically significant differences, indicating that both treatments effectively inhibited the abnormal activation of the Notch signaling pathway. Figure 8 The test results showed that, compared with the VPA group, the degree of neuronal degeneration in rats treated with serine and L-lysine salts (VPA+I group, VPA+II group) and single components (VPA+L,S, VPA+D,S, VPA+L,L) was reduced (p < 0.05). Moreover, the degree of neuronal degeneration in the salt groups was lower than that in the single component treatment groups, and the difference was statistically significant, indicating that compounds 1 and 2 have a attenuating effect on ASD-induced neuronal degeneration.

[0064] Recent research indicates that mutations or deletions of the NBEA (Neurobeachin) gene, a candidate gene for autism, are closely related to abnormal neurotransmitter release and synaptic transmission. The NBEA protein can interact with Notch1 / NICD, negatively regulating the Notch signaling pathway by modulating downstream transcriptional activity of the Notch receptor. Furthermore, increased Hes1 expression in the prefrontal cortex of VPA autism model mice further supports the important role of the Notch signaling pathway in the pathogenesis of autism.

[0065] The results of this experiment are highly consistent with previous reports, showing that the expression of Notch1 receptor, NICD, and its downstream transcription factor Hes1 in the hippocampus of VPA autism model mice was significantly upregulated, suggesting that activation of this signaling pathway may be involved in the pathological process of autism. Treatment with serine and L-lysine salts (I, II) significantly reduced the expression of related proteins, suggesting that it improved the neuromolecular abnormalities in the autism model by regulating the Notch1 / Hes1 signaling pathway. Furthermore, compared with the individual components (L-serine, D-serine, L-lysine), the two salt forms have advantages in stability and bioavailability, demonstrating good potential application value.

[0066] In conclusion, regulating the Notch signaling pathway may become a new target for autism treatment, and the salt formation of serine and L-lysine, as a novel nutritional intervention, shows promise in regulating this pathway and improving autism-related cognitive impairment.

[0067] The above description is merely a preferred embodiment of this application and is not intended to limit this application.

Claims

1. A serine and L-lysine salt, characterized in that, Having a structure as shown in Formula I or Formula II, 。 2. The serine and L-lysine salt according to claim 1, wherein the serine and lysine salt of Formula I is a crystal of the serine and lysine salt of Formula I, and its X-ray powder diffraction pattern using Cu ka radiation has diffraction peaks at the following 2θ angles: 18.444±0.2°, 19.006±0.2°, 22.837±0.2°, 28.272±0.2° and 30.265±0.2°.

3. The serine and L-lysine salts according to claim 2, wherein the crystals of the serine and lysine salts of Formula I have diffraction peaks at the following 2θ angles in their X-ray powder diffraction patterns using Cu ka radiation: 9.985±0.2°, 18.444±0.2°, 19.006±0.2°, 20.631±0.2°, 22.837±0.2°, 28.272±0.2°, 30.265±0.2°, 32.869±0.2°, 33.257±0.2°, and 34.943±0.2°.

4. The serine and L-lysine salt according to claim 3, wherein the serine and lysine salt represented by Formula II is a crystal of the serine and lysine salt represented by Formula II, and its X-ray powder diffraction pattern using Cu ka radiation has diffraction peaks at the following 2θ angles: 19.997±0.2°, 22.827±0.2°, 23.083±0.2°, 27.145±0.2° and 30.754±0.2°.

5. The serine and lysine salts according to claim 4, wherein the crystals of the serine and lysine salts of Formula II have diffraction peaks at the following 2θ angles in their X-ray powder diffraction patterns using Cu ka radiation: 6.818±0.2°, 18.658±0.2°, 19.997±0.2°, 20.794±0.2°, 22.051±0.2°, 22.827±0.2°, 23.083±0.2°, 28.477±0.2°, 30.754±0.2°, 33.510±0.2°, and 35.188±0.2°.

6. The serine and lysine salt according to claim 1, wherein the synthesis of the serine and lysine salt of formula I comprises the following steps: ， L-serine and L-lysine were dissolved in water, heated until dissolved, and then acetone was added dropwise to obtain product I.

7. The serine and lysine salts according to claim 1, wherein the synthesis of the D-serine and L-lysine salts represented by Formula II comprises the following steps: ， D-serine and L-lysine were dissolved in water, heated until dissolved, and then acetone was added dropwise to obtain product II.

8. The use of the serine and L-lysine salts according to any one of claims 1-7 in the preparation of medicaments for the prevention, treatment or improvement of nervous system diseases.

9. The application according to claim 8, wherein the neurological disorder is autism spectrum disorder.

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