Active peptide for improving brain injury and application

Abstract

The invention belongs to the technical field of active peptides, and particularly relates to an active peptide with a brain injury improving function and application of the active peptide, the amino acid sequence of the active peptide is shown as SEQ ID NO.1, and the active peptide can improve brain injury and has a good promoting effect on prognosis of brain injury patients.

Description

Technical Field

[0001] The present invention belongs to the technical field of active peptides, and in particular, the present invention relates to an active peptide having the function of improving brain damage and application thereof. Background Art

[0002] Brain injury is caused by trauma to the head and face, which in turn leads to damage to brain tissue. It is common in clinical practice and usually causes acute onset due to trauma. Typical symptoms include headache, impaired consciousness, and head hemorrhage. It generally requires conservative treatment or surgical treatment. The prognosis of mild patients is still good, while severe patients often have varying degrees of neurological deficits (limb paralysis, slurred speech, sensory impairment, etc.), and the prognosis is poor.

[0003] The prognosis of brain trauma is closely related to factors such as the severity of the injury, the patient's age and health status, timely treatment and rehabilitation measures. Generally speaking, the prognosis of mild brain trauma is more optimistic, while the prognosis of severe brain trauma is more severe. The prognosis of mild brain trauma is usually good, and patients can often recover completely after receiving appropriate treatment. Mild brain trauma generally manifests as a brief loss of consciousness after head injury or symptoms such as headache and dizziness, and usually does not leave obvious sequelae. The prognosis of severe brain trauma is often more complicated, and severe brain trauma may have long-term effects on the patient's physical and cognitive functions. Patients with severe brain trauma may experience long-term loss of consciousness, memory loss, language disorders, limb disability and other serious sequelae. At this time, the patient needs to receive comprehensive rehabilitation treatment and may require long-term care and support.

[0004] At present, common prognostic drugs for brain injury include isotonic whole protein formula (peptide) and the like. Peptides are helpful for brain nerve repair. Peptides can help activate the nervous system. They are also an important component of the brain tissue structure. They can provide raw materials for the physiological activities of brain cells and can increase the excitability of brain cells. Peptides have a certain effect of activating the nervous system. Therefore, when brain nerve damage occurs, peptides need to be supplemented during the repair process to help speed up the recovery of nerve function. At the same time, peptides are rich in lipids and unsaturated fatty acids, which are important components of the brain, so peptides can promote the repair of brain nerves. In addition, brain cells require a certain amount of energy consumption when performing physiological activities, and peptides can also provide sufficient raw materials, thereby promoting the development of brain cells and functional activities, which can help repair brain nerves. In addition, peptides can increase the excitability of brain cells, help fatigued or damaged brain cells recover faster, and prevent the sequelae of neurological dysfunction, so peptides are helpful for brain nerve repair.

[0005] However, most of the peptides commonly used are whole peptides, which often have poor effects when used by patients. There is still a need to find a small molecule peptide that can effectively prognose brain damage. Summary of the invention

[0006] In view of this, the present invention provides an active peptide with the function of improving brain injury, which can provide a good prognosis for patients with brain injury.

[0007] In the first aspect, the present invention provides an active peptide having the function of improving brain damage, and its amino acid sequence is shown as SEQ ID NO.1.

[0008] In a second aspect, the present invention provides a nucleic acid molecule encoding the active peptide according to the first aspect, or reversely complementary to the nucleotide sequence encoding the active peptide according to claim 1.

[0009] In a third aspect, the present invention provides a recombinant vector comprising the nucleic acid molecule described in the second aspect and capable of expressing the active peptide described in the first aspect.

[0010] In a fourth aspect, the present invention provides a host cell, the genome of which is incorporated with the nucleic acid molecule described in the second aspect and is capable of expressing the active peptide described in the first aspect.

[0011] In the fifth aspect, the present invention provides the use of the active peptide described in the first aspect, the nucleic acid molecule described in the second aspect, the recombinant vector described in the third aspect or the host cell described in the fourth aspect in the preparation of a drug for treating brain injury related diseases, wherein the brain injury related diseases include but are not limited to stroke, brain trauma and neurodegenerative diseases.

[0012] In a sixth aspect, the present invention provides a drug for treating brain injury-related diseases, comprising the active peptide described in the first aspect and a pharmaceutically acceptable excipient.

[0013] According to the drug described in the sixth aspect above, the excipients include one or more of a diluent, a preservative, a buffer, a disintegrant, an antioxidant, a suspending agent, and a colorant. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The preferred features, embodiments and variations of the present invention can be seen from the following detailed description, which provides sufficient information for those skilled in the art to perform the present invention. The detailed description should not be considered to limit the scope of the foregoing invention in any way.

[0015] Figure 1 This is a schematic diagram comparing the NSE fluorescence values ​​of zebrafish after each sample treatment in Example 5. DETAILED DESCRIPTION

[0016] The present invention will be further described in detail below in conjunction with specific examples, but the embodiments of the present invention are not limited to the scope represented by the examples. These examples are only used to illustrate the present invention, but are not used to limit the scope of the present invention. In addition, after reading the content of the present invention, those skilled in the art can make various modifications to the present invention, and these equivalent changes also fall within the scope limited by the appended claims of the present invention.

[0017] Related terms Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0018] "Small molecule peptides" are a kind of biochemical substance between amino acids and proteins. They have a smaller molecular weight than proteins and a larger molecular weight than amino acids. Small molecule peptides have a simple structure and a small molecular weight. They can be quickly absorbed through the small intestinal mucosa without the need for re-digestion or energy consumption, and have the characteristics of 100% absorption. Small molecule peptides can directly enter cells through the skin barrier, blood-brain barrier, placental barrier, and gastrointestinal mucosal barrier. Therefore, the absorption, conversion, and utilization of small molecule peptides are efficient and complete.

[0019] "Active peptides" specifically refer to peptide molecules with specific biological activity, whose functions are determined by their amino acid sequence and structure. The active peptides involved in the present invention have a small molecular weight and are small molecule peptides.

[0020] "Vector" refers to a nucleic acid carrier into which a polynucleotide can be inserted. When a vector can express the protein encoded by the inserted polynucleotide, the vector is called an expression vector. The vector can be introduced into a host cell by transformation, transduction or transfection, so that the genetic material elements it carries are expressed in the host cell. Vectors are well known to those skilled in the art, and include but are not limited to: plasmids; phagemids; cosmids; artificial chromosomes, such as yeast artificial chromosomes (YAC), bacterial artificial chromosomes (BAC) or P1-derived artificial chromosomes (PAC); bacteriophages such as lambda phage or M13 phage and animal viruses. Animal viruses that can be used as vectors include but are not limited to retroviruses (including lentiviruses), adenoviruses, adeno-associated viruses, herpes viruses (such as herpes simplex virus), poxviruses, baculoviruses, papillomaviruses, papillomas (such as SV40).

[0021] "Host cell" refers to a cell that can be used to introduce a vector, including but not limited to prokaryotic cells such as Escherichia coli or Bacillus subtilis, fungal cells such as yeast cells or Aspergillus, insect cells such as S2 Drosophila cells or Sf9, or animal cells such as fibroblasts, CHO cells, COS cells, NSO cells, HeLa cells, BHK cells, HEK 293 cells or human cells.

[0022] The small molecule peptide screened and constructed by the present invention can inhibit apoptosis and proliferation of brain tissue cells, improve damaged brain tissue, and reduce the expression of neuron-specific enolase.

[0023] The nucleic acid molecule of one embodiment of the present invention encodes the small molecule peptide as described above, namely the coding strand, or is the reverse complement of the nucleotide sequence encoding the small molecule peptide as described above, namely the antisense strand.

[0024] It is understandable that due to the degeneracy of codons, nucleic acid sequences that can express the same small molecule peptide have multiple forms. Technicians in the relevant field can determine the nucleic acid sequence through the codon table and further perform codon optimization to improve expression efficiency.

[0025] The recombinant vector according to one embodiment of the present invention contains the nucleotide sequence of the nucleic acid molecule as described above.

[0026] It is understood that the vector may also contain regulatory elements commonly used in genetic engineering, such as enhancers, promoters, etc. and other expression control elements (such as transcription termination signals, or polyadenylation signals and poly-U sequences, etc.).

[0027] The host cell according to one embodiment of the present invention has the above-mentioned nucleic acid molecule incorporated into its genome.

[0028] It is understood that the small molecule peptides, nucleic acid molecules, recombinant vectors or host cells described above can all be used to prepare products for treating brain injury-related diseases.

[0029] The method for preparing the above-mentioned small molecule peptide according to an embodiment of the present invention can be to artificially synthesize the small molecule peptide, or to obtain the small molecule peptide by gene expression using the above-mentioned host cell.

[0030] A drug for brain injury-related diseases according to an embodiment of the present invention comprises the above-mentioned small molecule peptide and pharmaceutically acceptable excipients.

[0031] In a specific example, the auxiliary material includes one or more of a diluent, a preservative, a buffer, a disintegrant, an antioxidant, a suspending agent, a colorant, and an excipient.

[0032] In a specific example, the diluent is selected from one or more of polyethylene glycol, propylene glycol, vegetable oil and mineral oil. In a specific example, the preservative is selected from one or more of sorbic acid, methyl sorbate, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, benzyl paraben, sodium methyl paraben, benzoic acid and benzyl alcohol. In a specific example, the buffer is selected from one or more of sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium citrate, sodium tartrate and sodium acetate. In a specific example, the disintegrant is selected from one or more of cross-linked carboxymethyl cellulose sodium, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone or low-substituted hydroxypropyl cellulose. In a specific example, the antioxidant is selected from one or more of ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetic acid, butylhydroxytoluene, glycine, inositol, ascorbic acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid and sodium pyrosulfite. In a specific example, the suspending agent is selected from one or more of beeswax, ethyl hydroxyethyl cellulose, chitin, chitosan, methyl cellulose, carboxymethyl cellulose, agar, hydroxypropyl methyl cellulose and xanthan gum. In a specific example, the colorant is selected from one or more of carbon black, iron black, iron brown, iron red and titanium dioxide. In a specific example, the excipient is selected from one or more of mannitol, glucose, lactose, dextran, dextran and sodium chloride.

[0033] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples are all commercially available unless otherwise specified.

[0034] Example 1: Preparation of small molecule peptides A method for preparing brain polypeptides and brain small molecule peptides by enzymatic hydrolysis of porcine brain, comprising the following steps: Step 1: Take out the fresh pig brain or the thawed frozen pig brain, wash it with pure water, and remove the fascia and blood vessels; mix the pig brain with pure water in a ratio of 1:1.5, grind it with a colloid mill, and adjust it to a finer fineness after the tissue is basically broken. Grind and homogenize for 5 minutes / batch, and then add 1.3 times the amount of pure water to continue homogenizing for 5 minutes. Mix each batch of homogenized brain slurry evenly, and adjust the pH value to 9.5 with potassium hydroxide solution; the coarsest mesh is 100 mesh; the finest mesh is 150 mesh; Step 2: placing the adjusted brain pulp homogenate in a microwave pot with a stirring device, controlling the temperature at 60°C, microwave for 20 minutes, and keeping warm for 15 minutes; the frequency of the microwave pot is 3300MHz, and the power is 25kW; discharging the microwave-treated homogenate, separating the protein and lipid twice at 38°C using a butterfly high-speed centrifuge, controlling the discharged light liquid to be 42% in the first centrifugation, and then microwave for 20 minutes after the discharged light liquid, and then centrifuging for the second time, the light liquid obtained by the second centrifugation is the phospholipid solution, and the concentrated liquid obtained by the two centrifugations is mixed; the speed of the first centrifugation is 9000 rpm; the speed of the second centrifugation is 12000 rpm; the temperature of the homogenate during the second centrifugation is not less than 38°C; Step 3: The mixed concentrated solution obtained in step 2 is adjusted to a pH value of 5.0 with dilute hydrochloric acid, so that the protein is precipitated in large cloud-like pieces and separated into layers, and then the liquid is removed by a 250-mesh filter cloth centrifuge, and the filter residue is collected to obtain brain protein isolate; the collected filter residue is dissolved in purified water twice the amount of the wet filter residue to obtain a 5% solution, the pH value is adjusted to 9.0, and then pancreatic enzyme (5000u / g) with a mass of 4.5% of the brain protein isolate is added to continue the homogenization cycle; when the pH value drops to about 7.5 again, alkali is added to adjust it to 8.6, and the solution is circulated for another 3 minutes, and the slurry is discharged; Step 4: before the slurry obtained in step 3 is sent to the microwave, the pH value is tested. When the pH value is less than 7, the pH value is adjusted to 8.2 by adding alkali, and microwave-assisted enzymolysis is performed, and the temperature is kept for 15 minutes to inactivate the enzyme; the inactivated enzymolysis solution is discharged, and when the temperature of the enzymolysis solution drops to less than 40° C., a 1.5% chitosan solution dissolved in 15% acetic acid is added under stirring, and the pH value is adjusted to 4.8, and unenzymatic brain protein, phospholipids and other macromolecular impurities are precipitated; the precipitate is centrifuged and filtered with a 200-mesh filter cloth to remove the precipitate; the centrifuge is filtered with a 0.25-micron hollow fiber membrane, and the filtrate is filtered with an ultrafiltration membrane that can intercept a molecular weight of 10,000 Da. The permeate is the pig brain polypeptide solution. If only polypeptides are used, the solution is concentrated under reduced pressure and then freeze-dried to obtain polypeptide powder; Step 5: Filter the polypeptide solution with a nanofiltration membrane with a molecular weight cutoff of 1200Da, concentrate the filtrate with a reverse osmosis membrane, freeze and dry the concentrate to obtain a small molecule brain peptide.

[0035] Example 2 LC-MS / MS separation and identification The amino acid sequence and molecular weight of the small molecule peptide component were determined by LC-MS / MS. The sample was first subjected to reduction alkylation and desalting treatment before loading. The capillary liquid chromatography column used was a 300μm×5mm AcclaimPepMapRPLC C18 analytical column (5μm), and the analytical column was a 150μm×150mm AcclaimPepMapRPLC C18 analytical column (1.9μm). Mobile phase A was 0.1% (v / v) formic acid solution and 2% (v / v) acetonitrile solution, and mobile phase B was 0.1% (v / v) formic acid solution and 80% (v / v) acetonitrile solution. The flow rate was 600nL / min, and the analysis time for each component was 60 minutes.

[0036] MS and MS / MS parameters are as follows: (1) MS parameters: resolution 70,000; maximum injection time 40 ms; scanning range 300-1400 m / z.

[0037] (2) MS / MS parameters: resolution 175000; maximum injection time 60 ms; scanning range 300-1400 m / z; Top N=20; NCE / steeped NCE=27.

[0038] The raw MS / MS files were analyzed by Mascot software according to the sample type to determine the amino acid sequence of the peptides.

[0039] After mass spectrometry data retrieval, PSM FDR≤0.01 and Protein FDR≤0.01 were used as screening criteria for peptide, site and protein identification, respectively, and 110 peptides were obtained for R4 component.

[0040] Example 3 Peptide screening, synthesis and verification 1. Peptide activity prediction Peptides were screened based on the probability of peptide mismatch (PEP), peptide match score (Score) and peptide peak intensity (Intensity), and those with zero score and intensity and too high mismatch rate were screened out. PeptideRanker was used to evaluate the possibility of peptides having biological activity and rank them. Among the 110 peptides, 54 peptides had scores greater than 0.5 and 12 peptides had scores greater than 0.9.

[0041] The biological activities of 74 short peptides with a PeptideRanker score greater than 0.5 were evaluated by searching the BIOPEP database, and the toxicity and pI values ​​of 54 short peptides were evaluated by Toxin Pred (toxicity prediction software) toxicity evaluation. Most short peptides have the potential or have antihypertensive (ACE inhibition, renin inhibition and vasoactive substance release activity), blood sugar lowering (DPP-IV inhibition, glucose absorption stimulation activity and α-glucosidase inhibition activity), pain control (DPP-Ⅲ inhibition activity) and AChE inhibition activity, and a few have antioxidant activity. Through evaluation, it was found that all 74 short peptides were non-toxic, and the pI value range was mostly between 5 and 7, and a few were between 9 and 11. 21 peptides were screened for molecular docking under the above conditions.

[0042] 2. Molecular docking Ligand processing: Chem3D 19.0 software was used to draw the molecular structure of the peptide, which was optimized by MM2 force field and saved as a pdb file. AutoDock software (molecular docking software) was used to import and hydrogenate the pdb file and save it as a pdbqt ligand file.

[0043] Receptor processing: The crystal structures of Fyn (2DQ7) and Keap 1 (6SP1) were downloaded from the PDB database, and the redundant chloride ions and water molecules were deleted using PyMOL software and saved as pdb files. The receptors 2DQ7 and 6SP1 were dehydrated and hydrogenated using AutoDock Tools software and saved as pdbqt receptor files for future use.

[0044] Molecular docking: Use the vina function of AutoDock Tools software to perform molecular docking and simulate the interaction between small peptide molecules and large protein molecules. Set the docking center coordinates of 2DQ7 to (-3.031, -9.266, 39.033) (x, y, z), the box size to 50×51×58, set the docking center coordinates of 6SP1 to (-26.315, 20.346, -16.173) (x, y, z), the box size to 51×51×49, and take the default values ​​for other parameters. Then, dock the amino acids and peptide ligands with the 2DQ7 crystal structure one by one.

[0045] Results: The 21 peptides screened above were docked with 2DQ7 and 6SP1 by Vina simulation, and 4 small molecule peptides were screened for synthetic verification according to the Vina scores.

[0046] Example 4 Synthesis and Activity Verification of Small Molecule Peptides 1. Synthesis The four small molecule peptides WTCFYE, LFLPR, WVA, and FFF were all synthesized by Sangon Biotech (Shanghai) Co., Ltd.

[0047] 2. Activity Verification Determination of reducing power: Each small molecule peptide was prepared into a 20 mg / mL solution, and the in vitro reducing power of the small molecule peptide was determined according to the method in Example 1. The relevant properties and antioxidant activity verification results of each small molecule peptide are shown in Table 1.

[0048] Table 1 Related properties of small molecule peptides and verification results of antioxidant activity

[0049] Note: (1) The reducing power is expressed as a percentage of 0.1 mg / mL BHA; (2) Due to the randomness of molecular docking results, the Vina score shown in the table is the average of the lowest values ​​of the 9 docking results (Note: the lower the score, the better the docking result).

[0050] As shown in Table 1, the small molecule peptide LFLPR has a strong reducing ability, and the vina score and peptide score are high.

[0051] Example 5 Detection of the efficacy of small molecule peptides in repairing brain damage 1. Experimental animals Wild-type AB strain zebrafish were bred in natural pairs. In this experiment, zebrafish larvae aged 4 days post fertilization (4 dpf) were selected to evaluate the effects of specific factors on their growth and development and related gene expression. All zebrafish were kept in special fish water maintained at 28°C. The water quality conditions were: 200 mg of instant sea salt was added to 1 L of reverse osmosis water, the conductivity was 450-550 μS / cm, the pH was 6.5-8.5, and the hardness was 50-100 mg / L CaCO 3 .

[0052] 2. Determination of the optimal detection concentration 4 dpf wild-type AB strain zebrafish were randomly selected in a 6-well plate, and 30 zebrafish were treated in each well. Different samples were given water-soluble, and a normal control group and a model control group were set up at the same time. The volume of each well was 3mL. Except for the normal control group, the other experimental groups were given aluminum chloride hexahydrate in water to establish a zebrafish brain damage model. After 48 hours of treatment at 28℃, the maximum tolerable concentration (MTC) of the sample for the model zebrafish was determined. The results are shown in Table 2 below.

[0053] Table 2 Maximum tolerance concentration of samples corresponding to each well plate

[0054] 3. Evaluation of neuron-specific enolase inhibitory efficacy Neuron-specific enolase (NSE) is an enzyme specific to neurons and neuroendocrine cells. As a sensitive indicator for evaluating the severity of nerve cell damage and judging prognosis, NSE is widely used in various nerve injuries, such as cerebral hemorrhage, ischemia, hypoxia, infection, poisoning, malnutrition, etc. At the same time, NSE is present in high levels in neuroendocrine cells, so it is often used in the diagnosis and prognosis of small cell lung cancer.

[0055] Under normal circumstances, serum and cerebrospinal fluid contain almost no NSE. Relevant studies in recent years have found that after cranial nerve damage, some neurons necrotize and then disintegrate, and the integrity of the cell membrane of the cranial nerve tissue is damaged, forcing NSE in the nerve cells to diffuse into the cerebrospinal fluid and intercellular space; due to the damage to the blood-brain barrier caused by the injury, its integrity is destroyed or its permeability is enhanced, and its natural barrier function is weakened, causing some protein components to be released into the blood and cerebrospinal fluid through the blood-brain barrier. After craniocerebral injury, the content of NSE in the blood and cerebrospinal fluid increases with the severity of craniocerebral injury, the more dead and disintegrated neuronal cells, and the more severe the damage to the blood-brain barrier. This mechanism has become the theoretical basis for detecting changes in NSE after brain neuron injury to judge the degree of nerve damage, and it is believed that NSE is a specific and sensitive detection indicator for judging the degree of craniocerebral injury and the prognosis of the disease.

[0056] Wild-type AB strain zebrafish were randomly selected in a 6-well plate, and 30 zebrafish were treated in each well. Different samples were given water-soluble, and the positive control was donepezil hydrochloride (concentration 3.33μg / mL). At the same time, a normal control group and a model control group were set up, and the volume of each well was 3 mL. Except for the normal control group, the other experimental groups were given aluminum chloride hexahydrate in water to establish a zebrafish brain injury model. After treatment at 28℃ for 48h, the NSE determination kit was used to collect data using a multifunctional microplate reader to analyze the NSE in zebrafish. The statistical analysis results of this indicator were used to evaluate the inhibitory efficacy of the samples on NSE. The statistical analysis results were expressed as mean±SE. SPSS 27.0 software was used for statistical analysis, where (*) indicates p<0.05, indicating that the difference is statistically significant; (**) indicates p<0.01, indicating that it is highly significant.

[0057] The results showed that under the experimental conditions, the small molecule peptides WTCFYE and LFLPR both had NSE inhibition effects, while the small molecule peptides WVA and FFF had no obvious NSE inhibition effects. Figure 1As shown in the figure, the inhibitory efficacy of the small molecule peptide WTCFYE is slightly lower than that of the small molecule peptide LFLPR, and the standard deviation of NSE corresponding to the small molecule peptide WTCFYE is larger, and relatively speaking, the standard deviation of NSE corresponding to the small molecule peptide LFLPR is smaller. Therefore, the present application prefers the small molecule peptide LFLPR, and its amino acid sequence is Leu-Phe-Leu-Pro-Arg, recorded as SEQID NO.1. The active peptide can improve brain damage and has a good promoting effect on the prognosis of patients with brain damage.

[0058] Further advantages and improvements may well be obtained without departing from the scope of the invention. Although the invention has been shown and described in terms of what are believed to be the most practical and preferred embodiments, it will be appreciated that departures may be made from the invention within the scope of the invention, and that the invention is not limited to the details disclosed herein but rather should be given the full scope of the claims to include any and all equivalent devices and apparatus. Any discussion of the prior art throughout the specification should not be taken as an admission that such prior art is well known or forms part of the common general knowledge in the field.

Claims

1. An active peptide for improving brain damage, characterized in that: Its amino acid sequence is shown in SEQ ID NO.

1.

2. A nucleic acid molecule, characterized in that It encodes the active peptide according to claim 1, or is reversely complementary to the nucleotide sequence encoding the active peptide according to claim 1.

3. A recombinant vector, characterized in that: Contains the nucleic acid molecule of claim 2 and is capable of expressing the active peptide of claim 1.

4. A host cell, characterized in that The nucleic acid molecule according to claim 2 is incorporated into its genome and can express the active peptide according to claim 1.

5. Use of the active peptide according to claim 1, the nucleic acid molecule according to claim 2, the recombinant vector according to claim 3 or the host cell according to claim 4 in the preparation of a drug for treating diseases related to brain injury.

6. A drug for treating brain injury-related diseases, characterized in that: The invention comprises the active peptide according to claim 1 and pharmaceutically acceptable excipients.

7. The drug according to claim 6, characterized in that The auxiliary materials include one or more of diluents, preservatives, buffers, disintegrants, antioxidants, suspending agents, and colorants.

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