Immunoregulation-nerve repair compound preparation as well as preparation method and application thereof

Abstract

The invention provides an immunoregulation-nerve repair composite preparation and a preparation method and application thereof.The preparation is composed of a nerve repair active component, an immunoregulation active component, an antioxidant active component and a sodium alginate-graphene oxide composite hydrogel carrier, and nerve nutrient substances such as nerve growth factors cooperate with components such as interleukin-10 and coenzyme Q10; the anti-inflammatory, anti-oxidation and nerve regeneration functions are realized; the graphene oxide loaded curcumin composite hydrogel carrier has the characteristics of targeted delivery and slow release. During preparation, the active components are dissolved step by step, then mixed with the carrier and oscillated and solidified in an alternating magnetic field, so that the stability and effectiveness of the preparation are ensured. The composite preparation can be used for auxiliary treatment of spinal cord injury, brain injury and other nerve injury diseases, and has a good application prospect in the field of nerve repair.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to an immunomodulatory-neural repair compound preparation, a preparation method thereof, and applications thereof. Background Art

[0002] Neurocritical care medicine is an important branch of critical care medicine, focusing on the diagnosis, treatment and monitoring of critical and severe neurological diseases, covering diseases that seriously threaten life or cause serious functional disorders, such as cerebral hemorrhage, cerebral infarction, severe brain trauma, spinal cord injury, central nervous system infection, status epilepticus, etc. These diseases are characterized by high morbidity, high mortality and high disability rates. The core pathological mechanisms include neuronal apoptosis, blood-brain barrier destruction, uncontrolled inflammatory cascade, oxidative stress damage, etc. For example, spinal cord injury is often accompanied by axonal rupture and glial scar formation, while triggering a severe immune inflammatory response, further aggravating nerve tissue damage. At present, the treatment methods for nerve injury mainly include surgical repair, physical therapy and drug intervention, but the existing technology still has many limitations.

[0003] In terms of drug treatment, traditional nerve repair drugs are mostly based on single neurotrophic factors, such as nerve growth factor (NGF). Although they can promote nerve cell survival to a certain extent, due to the complex local microenvironment and intense inflammatory response after nerve injury, a single ingredient cannot effectively counteract the inhibitory effect of inflammation on nerve regeneration, resulting in limited repair effects. In addition, neurotrophic factors have a short half-life and poor stability in the body, and cannot exert their effects continuously.

[0004] Existing immunomodulatory treatments often lack specificity and are unable to precisely regulate neuroinflammatory responses. Excessive suppression of immune function can lead to complications such as infection, while insufficient suppression can make it difficult to effectively mitigate secondary damage to neural tissue caused by inflammation.

[0005] In drug delivery systems, conventional carriers such as physiological saline and ordinary hydrogels have problems with poor targeting and weak sustained-release ability, making it difficult to effectively deliver drugs to the site of injury and maintain effective concentrations. At the same time, existing preparations rarely consider antioxidant factors and are unable to cope with the oxidative stress damage caused by the large amount of free radicals produced after nerve injury. Therefore, the development of a composite preparation that can synergistically achieve immune regulation, nerve repair and antioxidant functions, and has efficient drug loading performance, has become the key to solving the problem of nerve injury treatment. Summary of the Invention

[0006] In view of this, the present invention proposes an immunomodulatory-neural repair compound preparation and its preparation method and application to solve the above problems.

[0007] The technical solution of the present invention is achieved as follows: an immunoregulatory-neurorhealing composite preparation, comprising a neurorepair active ingredient, an immunoregulatory active ingredient, an antioxidant active ingredient and a pharmaceutically acceptable carrier, wherein the neurorepair active ingredient comprises nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), the immunoregulatory active ingredient comprises interleukin-10 and transforming growth factor-β1, and the antioxidant active ingredient comprises coenzyme Q10 and glutathione.

[0008] Furthermore, an immunoregulatory-neurorrepair compound preparation includes the following raw materials in parts by weight: 2-5 parts of nerve growth factor, 3-8 parts of brain-derived neurotrophic factor, 0.5-1.5 parts of glial cell line-derived neurotrophic factor, 0.8-1.9 parts of interleukin-10, 0.3-0.8 parts of transforming growth factor-β1, 0.3-0.5 parts of coenzyme Q10, 0.1-0.3 parts of glutathione, and 52-85 parts of a pharmaceutically acceptable carrier.

[0009] Furthermore, the pharmaceutically acceptable carrier comprises 2-7 parts of sodium alginate-graphene oxide composite hydrogel and 50-78 parts of normal saline, wherein the graphene oxide is loaded with curcumin.

[0010] Furthermore, the steps for constructing the sodium alginate-graphene oxide composite hydrogel are as follows:

[0011] A graphene oxide dispersion with a concentration of 0.5-1.0 mg / mL was mixed with curcumin at a mass ratio of 1:0.5-0.9, and ultrasonicated at 20-30 kHz, 120-180 W, 3-5 ° C in the dark for 10-20 minutes;

[0012] Add 2.0-3.0% w / v sodium alginate solution to the mixture obtained in step (a) at a rate of 0.5 mL / min and stir at 150-250 rpm and 25 ± 1°C.

[0013] 3.5-6.5 mM CaCl2 solution was added, and the mixture was stirred at a low speed of 40-60 rpm for cross-linking for 80-100 minutes to obtain a sodium alginate-graphene oxide composite hydrogel.

[0014] Furthermore, a method for preparing an immunomodulatory-neurorhealing composite preparation comprises the following steps:

[0015] S1. Dissolving nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in 1 / 3 part by weight of normal saline to obtain a nerve repair solution;

[0016] S2, dissolving interleukin-10 and transforming growth factor-β1 in 1 / 3 part by weight of normal saline to obtain an immunomodulatory solution;

[0017] S3, dissolving coenzyme Q10 and glutathione in the remaining physiological saline to obtain an antioxidant solution;

[0018] S4. The nerve repair solution obtained in step S1, the immunomodulatory solution obtained in step S2, and the antioxidant solution obtained in step S3 are sequentially added to the sodium alginate-graphene oxide composite hydrogel obtained in step S4, stirred and mixed, the pH value is adjusted to 6.5-7.5, and then oscillated and cured in an alternating magnetic field for 25-35 minutes to obtain the composite preparation.

[0019] Furthermore, the dissolution temperature in step S1, step S2 and step S3 is 20-30° C., the stirring speed is 100-300 rpm, and the dissolution time is 10-30 minutes.

[0020] Furthermore, in step S4, stirring is performed at 150-250 rpm for 20-40 minutes.

[0021] Furthermore, in step S4, the magnetic field frequency is 40-60 Hz and the intensity is 0.3-0.6T.

[0022] Furthermore, the immunomodulatory-neurorrepair compound preparation is used in the preparation of drugs for the auxiliary treatment of nerve damage diseases.

[0023] Furthermore, the nerve injury disease includes spinal cord injury, brain injury, and peripheral nerve injury.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] (1) Multi-component synergistic mechanism: This preparation integrates three types of active ingredients: neural repair, immune regulation, and antioxidant, to construct an "anti-inflammatory-antioxidant-promoting regeneration" synergistic system. In the neural injury microenvironment, immunomodulators precisely regulate the inflammatory response and reduce secondary damage; antioxidants scavenge free radicals and relieve oxidative stress; and neural repair factors promote cell survival and axon regeneration in the improved microenvironment, overcoming the functional limitations of single-component preparations.

[0026] (2) Targeted sustained-release carrier system: Sodium alginate-graphene oxide composite hydrogel is used as the drug delivery system, and graphene oxide is loaded with curcumin to achieve dual synergy. Graphene oxide achieves targeted delivery by specifically binding to the site of nerve damage; the anti-inflammatory and antioxidant properties of curcumin synergistically enhance the efficacy of the carrier. The three-dimensional network structure formed by sodium alginate and graphene oxide can effectively prolong the drug release cycle and maintain effective concentration at the damaged site, solving the problems of poor targeting and insufficient sustained-release capacity of traditional carriers.

[0027] (3) Standardized preparation process: The innovative preparation process uses a step-by-step dissolution method to ensure uniform dispersion of ingredients and stable activity. A composite hydrogel with uniform performance is constructed by precisely controlling the parameters of ultrasonic treatment, stirring, mixing, and cross-linking reactions. Alternating magnetic field oscillation curing technology further optimizes the hydrogel microstructure, improving mechanical strength and drug loading stability. This process is highly reproducible and provides technical support for industrial production.

[0028] (3) Broad-spectrum clinical applicability: This preparation is suitable for multiple types of injuries such as spinal cord, brain and peripheral nerves. It can achieve full neurological spectrum coverage through multiple administration routes and has a wider range of clinical application value and therapeutic potential compared to traditional therapies. DETAILED DESCRIPTION

[0029] In order to better understand the technical content of the present invention, specific examples are provided below to further illustrate the present invention.

[0030] Unless otherwise specified, the experimental methods used in the examples of the present invention are all conventional methods.

[0031] Unless otherwise specified, the materials, reagents, etc. used in the examples of the present invention can be obtained from commercial sources. Example 1

[0032] Preparation formula (by weight): 2 parts of nerve growth factor, 3 parts of brain-derived neurotrophic factor, 0.5 parts of glial cell line-derived neurotrophic factor, 0.8 parts of interleukin-10, 10.3 parts of transforming growth factor-β, 1.5 parts of hyaluronic acid, 0.5 parts of chitosan, 0.3 parts of coenzyme Q10, 0.1 parts of glutathione, 2 parts of sodium alginate-graphene oxide composite hydrogel, and 50 parts of normal saline.

[0033] Preparation method:

[0034] Sodium alginate-graphene oxide composite hydrogel construction;

[0035] 0.5 mg / mL graphene oxide dispersion was mixed with curcumin at a mass ratio of 1:0.5 and sonicated at 20 kHz, 120 W, and 3 °C in the dark for 10 min.

[0036] Add 2.0% w / v sodium alginate solution (addition rate 0.5 mL / min) and stir at 150 rpm and 25°C to mix;

[0037] Add 3.5 mM CaCl2 solution and stir at 40 rpm for 80 minutes for cross-linking.

[0038] (2) Preparation of compound preparations:

[0039] S1. Dissolve NGF, BDNF, and GDNF in 16.7 parts of normal saline and stir at 20°C and 100 rpm for 10 minutes to obtain a nerve repair solution.

[0040] S2. Dissolve interleukin-10 and transforming growth factor-β1 in 16.7 parts of normal saline, and stir at 20° C. and 100 rpm for 10 minutes to obtain an immunomodulatory solution;

[0041] S3, dissolving coenzyme Q10 and glutathione in the remaining saline solution, stirring at 20°C and 100 rpm for 10 minutes to obtain an antioxidant solution;

[0042] S4. Add the three solutions to the composite hydrogel, stir at 150 rpm for 20 minutes, and adjust the pH to 6.5; then place it in an alternating magnetic field with a frequency of 40 Hz and an intensity of 0.3 T for oscillation and curing for 25 minutes to obtain a composite preparation. Example 2

[0043] Preparation formula (by weight): 5 parts of nerve growth factor, 8 parts of brain-derived neurotrophic factor, 1.5 parts of glial cell line-derived neurotrophic factor, 1.9 parts of interleukin-10, 10.8 parts of transforming growth factor-β, 5 parts of hyaluronic acid, 2 parts of chitosan, 78 parts of normal saline, 0.5 parts of coenzyme Q10, 0.3 parts of glutathione, 7 parts of sodium alginate-graphene oxide composite hydrogel, and 78 parts of normal saline.

[0044] Preparation method:

[0045] (1) Construction of sodium alginate-graphene oxide composite hydrogel;

[0046] (a) A 1.0 mg / mL graphene oxide dispersion was mixed with curcumin at a mass ratio of 1:0.9 and sonicated at 30 kHz, 180 W, and 5°C in the dark for 20 min.

[0047] (b) Add 3.0% w / v sodium alginate solution (addition rate 0.5 mL / min) and stir at 250 rpm and 25°C to mix;

[0048] (c) Add 6.5 mM CaCl2 solution and stir at 60 rpm for 100 min.

[0049] (2) Preparation of compound preparations:

[0050] S1. Dissolve NGF, BDNF, and GDNF in 26 parts of normal saline and stir at 30°C and 300 rpm for 30 minutes to obtain a nerve repair solution.

[0051] S2, dissolving interleukin-10 and transforming growth factor-β1 in 26 parts of normal saline, and dissolving at 30° C. and stirring at 300 rpm for 30 minutes to obtain an immunomodulatory solution;

[0052] S3, dissolving coenzyme Q10 and glutathione in the remaining saline solution, stirring at 30°C and 300 rpm for 30 minutes to obtain an antioxidant solution;

[0053] S4. Add the three solutions to the composite hydrogel, stir at 250 rpm for 40 minutes, and adjust the pH to 7.5; then place it in an alternating magnetic field with a frequency of 60 Hz and an intensity of 0.6 T for oscillation and curing for 35 minutes to obtain a composite preparation. Example 3

[0054] Preparation formula (by weight): 3 parts of nerve growth factor, 5 parts of brain-derived neurotrophic factor, 1 part of glial cell line-derived neurotrophic factor, 1.2 parts of interleukin-10, 10.5 parts of transforming growth factor-β, 3 parts of hyaluronic acid, 1.2 parts of chitosan, 0.4 parts of coenzyme Q10, 0.2 parts of glutathione, 4 parts of sodium alginate-graphene oxide composite hydrogel, and 65 parts of normal saline.

[0055] Preparation method:

[0056] Sodium alginate-graphene oxide composite hydrogel construction;

[0057] 0.8 mg / mL graphene oxide dispersion was mixed with curcumin at a mass ratio of 1:0.7 and sonicated at 25 kHz, 150 W, and 4 °C in the dark for 15 min.

[0058] Add 2.5% w / v sodium alginate solution to the mixture (addition rate 0.5 mL / min) and stir at 200 rpm and 25°C;

[0059] 5 mM CaCl2 solution was added and cross-linked at a low speed of 50 rpm for 90 minutes to obtain a composite hydrogel.

[0060] (2) Preparation of compound preparations:

[0061] S1, dissolving nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, coenzyme Q10, and glutathione in 21.7 parts of normal saline, and dissolving at 25° C. and stirring at 200 rpm for 20 minutes to obtain a nerve repair solution;

[0062] S2, dissolving interleukin-10 and transforming growth factor-β1 in 21.7 parts of normal saline at 25° C. and stirring at 200 rpm for 20 minutes to obtain an immunomodulatory solution;

[0063] S3, dissolving coenzyme Q10 and glutathione in the remaining saline solution, stirring at 25°C and 200 rpm for 20 minutes to obtain an antioxidant solution;

[0064] S4. Add the nerve repair solution, immunomodulatory solution, and antioxidant solution to the composite hydrogel in sequence, stir at 25°C and 200 rpm for 20 minutes, and adjust the pH to 7.0; then place it in an alternating magnetic field with a frequency of 50 Hz and an intensity of 0.5 T for oscillation and curing for 30 minutes to obtain a composite preparation. Comparative Example 1

[0065] The difference between this comparative example and Example 3 is that the immunomodulatory active ingredients interleukin-10 and transforming growth factor-β1 are not added, and the remaining raw material compositions are the same as those of Example 3; Comparative Example 2

[0066] The difference between this comparative example and Example 3 is that the nerve repair active ingredients nerve growth factor, brain-derived neurotrophic factor and glial cell-derived neurotrophic factor are not added, and the remaining raw material compositions are the same as those in Example 3. Comparative Example 3

[0067] The difference between this comparative example and Example 3 is that glutathione is not added, the amount of coenzyme Q10 is increased to 0.6 parts, and the remaining raw material compositions and preparation steps are the same as those in Example 3. Comparative Example 4

[0068] The difference between this comparative example and Example 3 is that the carrier is not loaded with graphene oxide-curcumin, but is replaced by an equal amount of ordinary sodium alginate hydrogel.

[0069] Preparation method:

[0070] The steps for constructing the composite hydrogel were simplified as follows: directly cross-linking a 2.0% w / v sodium alginate solution with a 5 mM CaCl2 solution (without graphene oxide and curcumin), and the remaining steps were the same as in Example 3. Comparative Example 5

[0071] The difference between this comparative example and Example 3 is that alternating magnetic field curing is not used.

[0072] The raw material composition is the same as that of Example 3.

[0073] Preparation method: The "alternating magnetic field oscillation curing" step in S5 is omitted, and the preparation is obtained by simply stirring and mixing and then adjusting the pH. Test Example 1 - In vitro neurotrophic activity

[0074] 1. Test Method

[0075] Cell model: LPS-injured primary rat cortical neurons (simulating neuroinflammation)

[0076] 2. Group processing

[0077] Blank control (basal culture medium)

[0078] Example 1-3 Preparation

[0079] Comparative Example 1 (lack of immune regulatory factors)

[0080] Comparative Example 2 (missing nerve repair factor)

[0081] Comparative Example 4 (Ordinary Alginate Hydrogel Carrier)

[0082] 3. Detection indicators

[0083] Neuronal survival rate (Calcein-AM / PI double staining)

[0084] Synaptic density (Synapsin-1 immunofluorescence staining)

[0085] Mitochondrial membrane potential (JC-1 staining)

[0086] 4. Result Data

[0087]

[0088] (*p<0.01 vs Example 3; n=6)

[0089] Conclusion: The neuronal survival rate, synaptic density and mitochondrial membrane potential recovery rate of Examples 1-3 were significantly higher than those of the blank control group, among which Example 3 performed the best, indicating that the composite preparation can effectively promote neuronal survival, enhance synaptic connectivity and repair mitochondrial function, and has a positive effect on nerve damage repair.

[0090] All three indicators in Comparative Example 1 (no immunomodulatory ingredients) and Comparative Example 2 (no neurorepair ingredients) were significantly lower than those in the Example group (P < 0.05), confirming that neurorepair, immunomodulatory, and antioxidant active ingredients are essential in the formulation, and their synergistic effect is the core mechanism for achieving efficient neurorepair. The absence of immunomodulatory ingredients can affect the stability of the neural microenvironment, while the lack of neurorepair ingredients can effectively promote neuronal regeneration. The combined effect of these two ingredients maximizes the repair effect.

[0091] Comparative Example 4 (common carrier) achieved significantly lower performance than the Example group, demonstrating that the sodium alginate-graphene oxide composite hydrogel offers significant advantages over common carriers in improving the delivery efficiency of active ingredients and promoting nerve repair. Its unique structure and drug-carrying properties ensure optimal efficacy of the ingredients. Test Example 2 - Efficacy of Spinal Injury Model (Rats)

[0092] 1. Model establishment: The T10 spinal cord injury model was established using the Allen's heavy object drop method (25 g·cm impact force);

[0093] 2. Grouping: sham operation group, injury control group, Example 3 group, Comparative Example 3 group (glutathione deficiency), Comparative Example 5 group (no magnetic field curing);

[0094] 3. Detection indicators

[0095]

[0096] 4. Result Data

[0097]

[0098] (*p<0.01 vs Example 3; n=8)

[0099] Conclusion: The BBB score of the Example 3 group was significantly higher than that of the injury control group and close to the normal level of the sham operation group, indicating that the preparation can effectively improve the motor dysfunction after spinal cord injury; at the same time, the number of regenerated axons and the myelin integrity rate of the Example 3 group were significantly higher than those of the injury control group, confirming that it has an outstanding effect in promoting axon regeneration and myelin repair.

[0100] The TNF-α level, number of regenerated axons (49±4) and myelin integrity rate of the comparative example 3 group (lacking glutathione) were significantly lower than those of the example 3 group (P<0.05), indicating that the synergistic effect of antioxidant active ingredients is crucial for inhibiting inflammatory response (reducing TNF-α levels) and promoting nerve repair; adjustment of a single ingredient will weaken the overall efficacy of the preparation, highlighting the necessity of the synergistic effect of multiple ingredients.

[0101] All indicators of the comparative example 5 group (not using alternating magnetic field curing) were significantly lower than those of the example 3 group (P<0.05), proving that the alternating magnetic field curing process can optimize the structural properties of the sodium alginate-graphene oxide composite hydrogel, enhance the delivery efficiency and sustained release effect of the active ingredients, and thus improve the anti-inflammatory and nerve repair effects. Test Example 3-Carrier targeting and sustained release performance testing

[0102] 1. Fluorescent labeling preparation: Curcumin was labeled with Cy5 fluorescent dye and injected into the tail vein of rats with spinal cord injury (dose 10 μL / rat).

[0103] 2. In vivo imaging detection:

[0104] The fluorescence intensity at the lesion site was measured 1, 4, 12, and 24 h after injection to evaluate the targeting enrichment ability;

[0105] In vitro sustained-release experiment: The hydrogel was placed in PBS (pH 7.4, 37°C), and samples were taken at regular intervals to detect the cumulative release rates of NGF, IL-10, and curcumin.

[0106] 3. Experimental Results

[0107] The fluorescence intensity at the damaged site in Example 3 reached a peak at 12 hours and maintained a high signal at 24 hours, which was significantly higher than that in Comparative Example 4 (normal carrier, fluorescence decay >80% at 24 hours), demonstrating the targeting of graphene oxide.

[0108]

[0109] The sustained-release curve showed that the cumulative release rates of NGF / IL-10 were 60±5% and 61±3% at 72h, and the release rate of curcumin was 75±6% at 96h, while the release rate of the control group 4 was >90% at 24h, proving the sustained-release advantage of the composite hydrogel.

[0110] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. An immunomodulatory-neurorhealing compound preparation, characterized by: The invention comprises a neurorepair active ingredient, an immunomodulatory active ingredient, an antioxidant active ingredient and a pharmaceutically acceptable carrier. The neurorepair active ingredient comprises nerve growth factor, brain-derived neurotrophic factor and glial cell-derived neurotrophic factor; the immunomodulatory active ingredient comprises interleukin-10 and transforming growth factor-β1; and the antioxidant active ingredient comprises coenzyme Q10 and glutathione.

2. The immunomodulatory-neurorhealing compound preparation according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 2-5 parts of nerve growth factor, 3-8 parts of brain-derived neurotrophic factor, 0.5-1.5 parts of glial cell line-derived neurotrophic factor, 0.8-1.9 parts of interleukin-10, 0.3-0.8 parts of transforming growth factor-β1, 0.3-0.5 parts of coenzyme Q10, 0.1-0.3 parts of glutathione, and 52-85 parts of a pharmaceutically acceptable carrier.

3. The immunomodulatory-neurorhealing composite preparation according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: the pharmaceutically acceptable carrier comprises 2-7 parts of sodium alginate-graphene oxide composite hydrogel and 50-78 parts of normal saline, wherein the graphene oxide is loaded with curcumin.

4. The immunomodulatory-neurorhealing composite preparation according to claim 3, characterized in that: The steps for constructing the sodium alginate-graphene oxide composite hydrogel are as follows: (a) A graphene oxide dispersion having a concentration of 0.5-1.0 mg / mL was mixed with curcumin in a mass ratio of 1:0.5-0.9 and sonicated at 20-30 kHz, 120-180 W, 3-5°C in the dark for 10-20 min; (b) adding 2.0-3.0% w / v sodium alginate solution to the mixture obtained in step (a) at a rate of 0.5 mL / min and stirring at 150-250 rpm and 25 ± 1°C; (c) Add 3.5-6.5 mM CaCl2 solution and stir at a low speed of 40-60 rpm for cross-linking for 80-100 minutes to obtain sodium alginate-graphene oxide composite hydrogel.

5. A method for preparing an immunomodulatory-nerve repair composite preparation according to any one of claims 1 to 4, characterized in that: The following steps are involved: S1. Dissolving nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in 1 / 3 part by weight of normal saline to obtain a nerve repair solution; S2, dissolving interleukin-10 and transforming growth factor-β1 in 1 / 3 part by weight of normal saline to obtain an immunomodulatory solution; S3, dissolving coenzyme Q10 and glutathione in the remaining physiological saline to obtain an antioxidant solution; S4. The nerve repair solution obtained in step S1, the immunomodulatory solution obtained in step S2, and the antioxidant solution obtained in step S3 are sequentially added to the sodium alginate-graphene oxide composite hydrogel obtained in step S4, stirred and mixed, the pH value is adjusted to 6.5-7.5, and then oscillated and cured in an alternating magnetic field for 25-35 minutes to obtain the composite preparation.

6. The method for preparing an immunomodulatory-nerve repair compound preparation according to claim 5, characterized in that: The temperature during dissolution in step S1, step S2 and step S3 is 20-30° C., the stirring speed is 100-300 rpm, and the dissolution time is 10-30 minutes.

7. The method for preparing an immunomodulatory-nerve repair composite preparation according to claim 5, characterized in that: In step S4, the mixture is stirred at 150-250 rpm for 20-40 minutes.

8. The method for preparing an immunomodulatory-nerve repair compound preparation according to claim 5, wherein: In step S4, the magnetic field frequency is 40-60 Hz and the intensity is 0.3-0.6 T.

9. Use of the immunomodulatory-nerve repair compound preparation according to any one of claims 1 to 4 in the preparation of a drug for the auxiliary treatment of nerve damage diseases.

10. The use according to claim 9, characterized in that The nerve injury diseases include spinal cord injury, brain injury, and peripheral nerve injury.

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