Antioxidant nanoparticle-gel preparation capable of specifically consuming microglial cells in craniocerebral injury area as well as preparation method and application of antioxidant nanoparticle-gel preparation

Abstract

The invention provides an antioxidant nanoparticle-gel preparation capable of specifically consuming microglial cells in a craniocerebral injury area, and the antioxidant nanoparticle-gel preparation is prepared from PLX5622 nanoparticles, methacrylic acid gelatin, methacrylic acid polypropylene sulfide and phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate. The invention also provides a preparation method of the antioxidant nanoparticle-gel preparation. The preparation method comprises the following steps: weighing the raw materials; and mixing, dissolving in a phosphate buffer solution, fully stirring, removing bubbles, and completely dissolving to obtain the antioxidant nanoparticle-gel preparation. The invention also provides an application of the antioxidant nanoparticle-gel preparation in preparation of a medicine for treating traumatic brain injury. The hydrogel can respond in a craniocerebral trauma microenvironment, consume active oxygen in the microenvironment after trauma and is gradually degraded, meanwhile, the hydrogel is further disintegrated, the PLX5622 nanoparticles entrapped in the hydrogel are released and enriched to a trauma area, microglial cells are consumed, and neuroinflammation after trauma is relieved.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine and relates to a drug for treating traumatic brain injury, specifically an antioxidant nanoparticle-gel preparation that can specifically consume microglia in a craniocerebral injury area, and a preparation method and application thereof. Background Art

[0002] Due to its high morbidity, mortality and disability rates, craniocerebral trauma has become a serious public health problem worldwide. Although the understanding of the pathogenesis of craniocerebral injury has been continuously deepened, new drugs have been continuously increased and new technologies have been gradually applied, the level of treatment for patients with craniocerebral trauma has been significantly improved. However, in the process of treating TBI patients, the more prominent problem is how to deal with excessive oxidative stress and neuroinflammation after primary brain injury. Excessive oxidative stress and neuroinflammation lead to edema formation and tissue swelling, persistent damage to the blood-brain barrier, and thus lead to secondary injury problems such as persistent neurological disorders. Therefore, it is particularly important to develop safe and reliable craniocerebral protective drugs.

[0003] At present, it is believed that reactive oxygen species are certain metabolites of oxygen and oxygen-containing products of some reactions, mainly single-electron reduced products of oxygen (O 2- , O - ) and their protonated forms, two-electron reduced forms of oxygen (H 2 O 2 ), alkane peroxide ROOH and its homolytic products, etc. The brain is an organ with high oxygen and energy consumption. After brain trauma, nerve cells need a lot of oxygen and energy for self-repair, which leads to the breakdown of the balance between oxygen and energy supply and demand, resulting in excessive oxidative stress and the production of a large amount of reactive oxygen. The damage of reactive oxygen to the body is mainly reflected in the destructive effect on cell membranes. Nerve cells and cerebral vascular endothelial cells are the most severely damaged parts. Reactive oxygen mainly attacks the cell membrane with lipid bilayer and polyunsaturated fatty acids as the framework, destroys various ion pumps on the membrane, and causes the disorder of the intracellular environment; destroys the collagen and basement membrane of vascular endothelial cells, resulting in increased permeability of the blood-brain barrier; attacks vascular smooth muscle, resulting in smooth muscle relaxation, vasodilation and microcirculation disorders, and aggravates cerebral edema. Therefore, how to consume and inhibit the reactive oxygen produced during craniocerebral trauma is a key issue in the treatment of craniocerebral trauma.

[0004] On the other hand, neuroinflammatory response is an important link that affects the prognosis of craniocerebral trauma. Neuroinflammatory response after craniocerebral trauma is a double-edged sword: it has a beneficial side, such as promoting the removal and regeneration of debris by mediating neuronal death and progressive neurodegeneration; it also has a harmful side, such as excessive secretion of cytokines and chemokines that can lead to BBB destruction, prolong the inflammatory process, and further induce chronic neurodegeneration. How to "seek benefits and avoid harm" in neuroinflammatory response is our difficulty in treating patients with craniocerebral trauma, and it is also the focus of current research and exploration. As resident immune cells of the central nervous system, microglia play an important role in the occurrence and development of neuroinflammatory response. Excessive activation and proliferation of microglia can aggravate neuroinflammation, and the persistent inflammatory state can eventually cause neurological dysfunction and neurodegeneration after TBI.

[0005] Under physiological conditions, microglia are the only cell type in the central nervous system that expresses CSF1R, and CSF1R is an important pathway for maintaining microglia survival and proliferation in adult individuals. PLX5622, as a small molecule CSF1R inhibitor, has good selectivity for microglia and can achieve continuous and specific elimination of microglia. However, PLX5622 still has many defects and deficiencies in practical applications. The details are as follows:

[0006] ① Lack of ability to locally remove microglia in the lesion;

[0007] ② Systemic application will lead to the consumption of peripheral bone marrow-derived mononuclear macrophages;

[0008] ③Continuous oral administration can significantly affect the intestinal microbiota;

[0009] ④The first-pass effect of oral administration reduces the bioavailability of the drug. Summary of the invention

[0010] In view of the above-mentioned technical problems in the prior art, the present invention provides an antioxidant nanoparticle-gel preparation that can specifically consume microglia in the craniocerebral injury area, and a preparation method and application thereof. The nanoparticle-gel preparation that can treat traumatic brain injury, and a preparation method and application thereof are intended to solve the technical problems in the prior art of using PLX5622 in the treatment of craniocerebral trauma, such as lack of targeting, multiple side effects, and low bioavailability.

[0011] The present invention provides an antioxidant nanoparticle-gel preparation for specifically consuming microglia in a craniocerebral injury area, which is prepared from a PLX5622 nanoparticle solution, methacrylated gelatin, methacrylated polypropylene sulfide, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate, wherein the mass volume ratio of the PLX5622 nanoparticle solution, methacrylated gelatin, methacrylated polypropylene sulfide, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate is 1 mL: 40-60 mg: 15-25 mg: 4-6 mg;

[0012] In the PLX5622 nanoparticle solution, the structural formula of the PLX5622 is as follows:

[0013]

[0014] Furthermore, the PLX5622 nanoparticle solution is prepared from the following raw materials in the following mass ratio:

[0015] The structural formula of PLX5622 is shown below.

[0016]

[0017] Furthermore, the preparation method of the PLX5622 nanoparticle solution comprises the following steps:

[0018] 1) Weigh lecithin, phospholipid-polyethylene glycol, cysteine-alanine-lysine glutamine-phospholipid-polyethylene glycol and PLX5622 according to the mass ratio;

[0019] 2) Mix the above substances and dissolve them in dimethyl sulfoxide, shake them in a vortex mixer to fully dissolve the components, place the centrifuge tube containing the phosphate buffer solution in a heat-collecting constant temperature heating magnetic stirrer, drop the above mixture into it under stirring, and then maintain the stirring state for 1 to 3 hours to form a PLX5622 nanoparticle solution.

[0020] The present invention also provides a method for preparing the above-mentioned antioxidant nanoparticle-gel preparation for specifically consuming microglia in the craniocerebral injury area, comprising the following steps:

[0021] 1) Weighing methacrylated gelatin, methacrylated polypropylene sulfide, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate, and PLX5622 nanoparticle solution according to mass volume ratio;

[0022] 2) Methacrylated gelatin, methacrylated polypropylene sulfide, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate are mixed and dissolved in a PLX5622 nanoparticle solution, and the mixture is stirred thoroughly at room temperature and protected from light to remove bubbles so that the mixture is completely dissolved into a clear liquid, thereby preparing an antioxidant nanoparticle-gel preparation that specifically consumes microglia in the craniocerebral injury area.

[0023] The present invention also provides the use of the above-mentioned antioxidant nanoparticle-gel preparation for specifically consuming microglial cells in the craniocerebral injury area in the preparation of a medicine for treating craniocerebral trauma.

[0024] The present invention also provides a compound, the structural formula of which is shown below:

[0025] The compound name is methacrylated polypropylene sulfide.

[0026] The present invention also provides a method for preparing the above-mentioned compound, comprising the following steps:

[0027] 1) In a dry, nitrogen-flushed container, 1,8-diazabicyclo[5.4.0]undec-7-ene in dry tetrahydrofuran is degassed, and the temperature of the reaction mixture is lowered to 0°C, a degassed 1-butanethiol solution in tetrahydrofuran is added dropwise to the container and reacted, and then freshly distilled and degassed propylene sulfide monomer is added to the reaction mixture, and the temperature is maintained at 0°C for 1 to 3 hours, the reaction is quenched by adding 2-iodoethanol, and stirred at room temperature overnight, after 12 to 24 hours, the polymer solution is filtered to remove salt precipitation, and is purified by precipitation into cold methanol, and finally vacuum dried to produce a colorless viscous polymer;

[0028] 2) The colorless viscous polymer of step 1) is dissolved in a mixed solution of dichloromethane and triethylamine, freshly distilled methacryloyl chloride is added dropwise at 0°C, and the reaction mixture is stirred overnight under argon. The reaction solution is transferred to a dialysis bag with a molecular weight cutoff of 2000Da, and dialyzed in pure water for 12 to 48 hours. The dialyzate is collected and freeze-dried in a freeze dryer to obtain the product methacrylated polypropylene sulfide.

[0029] The reaction equation of the above preparation method is as follows:

[0030]

[0031] The antioxidant nanoparticle-gel preparation of the present invention, which is targeted at consuming microglia in a craniocerebral injury area, is prepared by mixing PLX5622 nanoparticles, methacrylated gelatin, methacrylated polypropylene sulfide and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate, and then self-assembling into a nanoparticle-hydrogel complex in a post-traumatic brain tissue site in response to blue light of a specific wavelength.

[0032] The PLX5622, as a type of small molecule CSF1R inhibitor, has good selectivity for microglia and can achieve sustained and specific elimination of microglia, but systemic application has many side effects and low bioavailability.

[0033] The methacrylated gelatin is a photosensitive biohydrogel material, which can be stimulated by light of a fixed wavelength to undergo a curing reaction, has the advantages of good biocompatibility, is degradable, and has an easily controllable degradation rate, and is safe and reliable. Its structural formula is as follows:

[0034]

[0035] The polysulfide unit in the methacrylated polypropylene sulfide can respond to and consume active oxygen in an active oxygen environment, and at the same time utilizes thioacetal coupling methacrylic acylation to prepare methacrylated polypropylene sulfide; its structural formula is as follows:

[0036]

[0037] In order to overcome the systemic toxic side effects caused by systemic application of PLX5622, reduce the accumulation of reactive oxygen in the post-traumatic microenvironment, and overcome the low drug utilization caused by the existence of the blood-brain barrier, a hydrogel with the function of consuming reactive oxygen is used for local drug delivery of PLX5622 nanoparticles to inhibit excessive oxidative stress. At the same time, PLX5622 nanoparticles specifically consume microglia in the injured area to control neuroinflammation and exert a neuroprotective effect.

[0038] As a photoinitiator with excellent biocompatibility, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate can initiate free radical polymerization under ultraviolet light at 405 nm, so that the components of the gel preparation can self-assemble at the lesion to form a hydrogel to exert its effect.

[0039] In order to overcome the systemic toxic side effects caused by systemic application of PLX5622 and reduce the accumulation of reactive oxygen in the post-traumatic microenvironment, the present invention provides a method for preparing an antioxidant nanoparticle-gel preparation that can specifically consume microglia in the craniocerebral injury area; the strategy of "hydrogel with the function of consuming reactive oxygen species controls neuroinflammation and synergistically treats craniocerebral trauma by specifically consuming microglia in the injured area" is adopted to design and prepare nanoparticle-hydrogel, so that the hydrogel with the function of consuming reactive oxygen species is equipped with PLX5622 nanoparticles to specifically consume microglia in the injured area to control neuroinflammation and synergistically treat secondary brain injury.

[0040] The specific treatment steps of the present invention are as follows: ① In situ injection of nanoparticle-gel preparation, and cross-linking under blue light to form a gel state, tightly attached to the trauma area; ② The gel responds to the reactive oxygen in the microenvironment after trauma and gradually degrades; ③ Methacrylated polysulfide responds to and consumes reactive oxygen to exert an antioxidant effect, while causing further disintegration of the hydrogel, and the PLX5622 nanoparticles encapsulated in the gel are released, and the post-traumatic neuroinflammation is alleviated by targeted consumption of microglia. Finally, the functional hydrogel and PLX5622 nanoparticles synergistically inhibit neuroinflammation by consuming reactive oxygen and exert a neuroprotective effect. The in situ injection method can avoid the toxic and side effects of systemic drugs, overcome the blood-brain barrier, and increase the concentration of drugs in the local brain trauma, timely and effectively improve the effect of craniocerebral trauma treatment, and improve the level of craniocerebral trauma treatment.

[0041] Compared with the prior art, the technical effect of the present invention is positive and obvious. The antioxidant nanoparticle-gel preparation of the present invention that specifically consumes microglia in the craniocerebral injury area has intelligent light responsiveness, realizes stable gelation after in situ injection at the site of craniocerebral trauma, and avoids systemic toxic side effects. The nanoparticle-gel preparation of the present invention can respond to the reactive oxygen in the post-traumatic microenvironment in the microenvironment of craniocerebral trauma and gradually degrade, while methacrylated polypropylene sulfide responds to and consumes reactive oxygen to exert an antioxidant effect, leading to further disintegration of the hydrogel, and realizing the controlled release of PLX5622 nanoparticles to specifically consume microglia in the injured area. The nanoparticle-gel preparation of the present invention can consume reactive oxygen and microglia, reduce oxidative stress and neuroinflammation, and thus exert a neuroprotective effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 The structure of the PLX5622 nanoparticle solution prepared by the present invention (bar=100 nm).

[0043] Figure 2 The structure of the methacrylated polypropylene sulfide prepared by the present invention.

[0044] Figure 3 The nano-gel preparation prepared by the invention has good injectability and intelligent light-responsive gelling properties in vivo.

[0045] Figure 4 Scanning electron microscopy showed the internal structure of the nano-gel preparation prepared in the present invention (bar=20 μm).

[0046] Figure 5 The drug release characteristics of the nano-gel preparation prepared by the invention.

[0047] Figure 6 The degradation and release of the nano-gel preparation prepared by the present invention at the injured part of mice after trauma (bar=100 μm).

[0048] Figure 7 The nano-gel preparation prepared by the present invention can effectively reduce the oxidative stress level (bar=50 μm).

[0049] Figure 8 The nano-gel preparation prepared by the present invention can effectively consume microglial cells in the damaged area.

[0050] Fig. 9 The nano-gel preparation prepared by the present invention has the effect of improving neuroinflammation (bar=200 μm).

[0051] Fig.10 The nano-gel preparation prepared by the present invention has the effect of alleviating brain tissue edema (bar=200 μm).

[0052] Fig.11 The nano-gel preparation prepared by the invention has the function of protecting the blood-brain barrier.

[0053] Fig.12 The nano-gel preparation prepared by the invention has the effect of improving nerve function. DETAILED DESCRIPTION

[0054] The present invention is further described below in conjunction with embodiments.

[0055] Example 1: Preparation of Nanoparticle-Gel Formulation

[0056] The PLX5622 nanoparticle solution was prepared as follows:

[0057] According to the mass ratio, 0.1 mg of lecithin, 0.2 mg of polylactic acid-glycolic acid, 0.1 mg of phospholipid-polyethylene glycol, 0.04 mg of cysteine-alanine-lysine glutamine-phospholipid-polyethylene glycol and 0.1 mg of PLX5622 (from MedChemExpress) were weighed.

[0058] The above substances were mixed and dissolved in 200 μL of dimethyl sulfoxide, and shaken on a vortex mixer to fully dissolve the components. A centrifuge tube containing phosphate buffer solution (800 μL) was placed in a heat-collecting constant temperature heating magnetic stirrer, and the above mixture was slowly dripped in under high-speed stirring at 25°C, and then maintained under slow stirring at 25°C for about 2 hours to form a PLX5622 nanoparticle solution.

[0059] like Figure 1 Shown is the structure of PLX5622 nanoparticle solution.

[0060] The preparation method of methacrylated polypropylene sulfide is as follows:

[0061] In a dry, nitrogen-flushed round-bottom flask, 1,8-diazabicyclo[5.4.0]undec-7-ene (3 mmol, 0.448 mL) in dry 15 mL tetrahydrofuran was degassed for 30 min and the reaction mixture temperature was lowered to 0°C. A 30 min degassed 1-butanethiol solution (1.0 mmol, 0.070 mL) in 10 mL tetrahydrofuran was added dropwise to the flask and allowed to react for 30 min. Freshly distilled and degassed propylene sulfide (60 mmol, 4.68 mL) monomer was then added to the reaction mixture and the temperature was maintained at 0°C for 2 hours. The reaction was quenched by the addition of 2-iodoethanol (2 mmol, 0.37 g) and stirred overnight at room temperature. The next day, the polymer solution was filtered to remove salt precipitates and further purified by three precipitations into cold methanol and finally dried under vacuum to produce a colorless viscous polymer (3.8 g, 85.6%). The colorless viscous polymer (0.8 mmol, 3 g) was dissolved in dichloromethane (25 mL) and triethylamine (5 mL). Freshly distilled methacryloyl chloride (125 mg, 1.2 mmol) was added dropwise at 0°C, and the reaction mixture was stirred overnight under argon. The reaction solution was transferred to a dialysis bag (molecular weight cutoff 2000 Da), dialyzed in pure water for 24 h, and the dialyzate was collected and freeze-dried in a freeze dryer to obtain the product methacrylated polypropylene sulfide (1.8 g, 60.0%).

[0062] like Figure 2 Shown is the structure of methacrylated polypropylene sulfide.

[0063] Use an analytical balance to weigh 50 mg of methacrylated gelatin, 20 mg of methacrylated polypropylene sulfide, and 5 mg of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate, dissolve them in 1 ml of PLX5622 nanoparticle solution, stir them thoroughly at room temperature and in the dark to remove bubbles, and completely dissolve them into a clear liquid to prepare a nanoparticle-gel preparation.

[0064] Example 2: Injectability and in vivo self-assembly gel properties of nanoparticle-gel formulations.

[0065] An appropriate amount of the nanoparticle-gel preparation of Example 1 was taken to perform an in situ gelation experiment on a craniocerebral trauma mouse model to observe its injectability and gelation properties.

[0066] like Figure 3 As shown, the nanoparticle-gel preparation prepared by the present invention has good injectability and in vivo intelligent light-responsive gelation properties.

[0067] Example 3: Micromorphology of Nanoparticle-Gel Formulations

[0068] Take an appropriate amount of the nanoparticle-gel preparation of Example 1, and after forming a gel under 405 nm blue light, place it in liquid nitrogen and quickly freeze it to a solid state, immediately put it in a freeze dryer and freeze-dry it for 48 hours, take it out and fix it on an aluminum plate, spray it with gold and observe it with a scanning electron microscope.

[0069] like Figure 4 As shown, the internal structure of the hydrogel prepared by the present invention is shown by scanning electron microscopy (bar=200 μm). Scanning electron microscopy reveals that the gel has a porous structure inside, which provides a structural basis for the gel to be used as a drug carrier.

[0070] Example 4: Drug release characteristics of nanoparticle-gel formulations

[0071] The drug release from the hydrogel was measured by high performance liquid chromatography. Figure 5 As shown, the drug release characteristics of the hydrogel nanoparticle-gel preparation prepared in Example 1 of the present invention. The nanoparticle-hydrogel can exert its effect by releasing the loaded PLX5622 in response to the microenvironment after injury.

[0072] Example 5: Degradation and release of nano-gel preparations at the injured site of mice after trauma

[0073] C57 male mice (Jiangsu Jicui Pharmaceutical Biotechnology Co., Ltd.) were selected as experimental animals and were used for animal experiments after pre-adaptive feeding. The experimental animals were kept in independent ventilation isolation cages, the room temperature was controlled at 23±2℃, and regular light was maintained, and water and food were adequately supplied. Brain tissue sections were used to observe the degradation and release ability of nanoparticle-gel in vivo after craniocerebral trauma surgery. Figure 6 .

[0074] like Figure 6 As shown, the nano-gel preparation prepared in Example 1 of the present invention degrades and releases drugs at the site of craniocerebral trauma (bar=200 μm).

[0075] Example 6: Nano-gel formulation can effectively reduce oxidative stress levels

[0076] Dihydroethidium staining was used to evaluate the level of neuronal apoptosis around the traumatic brain lesion. Figure 7 (TBI: untreated group after traumatic brain injury; GelMA-PPS / P: treated group after traumatic brain injury with nano-gel preparation).

[0077] like Figure 7 As shown, the nano-gel preparation prepared in Example 1 of the present invention can effectively reduce the oxidative stress level (bar=200 μm).

[0078] Example 7: Nano-gel preparation can effectively deplete microglia in the injured area

[0079] PET-CT was used to evaluate the level of microglia in the brain injury area. Figure 8 (TBI: untreated group after traumatic brain injury; GelMA-PPS / P: treated group after traumatic brain injury with nano-gel preparation).

[0080] like Figure 8 As shown, the nano-gel preparation prepared in Example 1 of the present invention can effectively consume microglia in the injured area.

[0081] Example 8: Nano-gel preparation can effectively improve neuroinflammation

[0082] Immunohistochemical staining was used to detect glial cell / macrophage specific protein (Iba-1) and glial fibrillary acidic protein (GFAP) to evaluate the level of peripheral neuroinflammation in craniocerebral trauma. Fig. 9 (TBI: untreated group after traumatic brain injury; GelMA-PPS / P: treated group after traumatic brain injury with nano-gel preparation).

[0083] like Fig. 9 As shown, the nano-gel preparation prepared in Example 1 of the present invention can effectively improve neuroinflammation.

[0084] Example 9: Nano-gel preparation has the effect of alleviating brain tissue edema

[0085] The anti-edema effect of nano-gel preparations after craniocerebral trauma was evaluated using 7T small animal MRI. Fig.10 (Control: untreated group with craniocerebral trauma; GelMA-PPS / P: group treated with nano-gel preparation after craniocerebral trauma).

[0086] like Fig.10 As shown, the nano-gel preparation prepared in Example 1 of the present invention has the effect of alleviating brain tissue edema.

[0087] Example 10: Nano-gel preparation has the effect of protecting the blood-brain barrier

[0088] Evans blue absorption was used to evaluate the protective effect of nano-gel preparations on the blood-brain barrier after craniocerebral trauma. Fig.11 (TBI: untreated group after traumatic brain injury; GelMA-PPS / P: treated group after traumatic brain injury with nano-gel preparation).

[0089] like Fig.11 As shown, the nano-gel preparation prepared in Example 1 of the present invention has the effect of protecting the blood-brain barrier.

[0090] Example 11: Nano-gel preparation has the effect of improving nerve function

[0091] The Barnes maze was used to evaluate the improvement of learning and memory ability of nano-gel preparations after traumatic brain injury. Fig.12 (TBI: untreated group after traumatic brain injury; GelMA-PPS / P: treated group after traumatic brain injury with nano-gel preparation).

[0092] like Fig.12 As shown, the nano-gel preparation prepared in Example 1 of the present invention has the effect of improving nerve function.

Claims

1. An antioxidant nanoparticle-gel preparation for targeted consumption of microglia in craniocerebral injury areas, characterized in that: It is prepared from PLX5622 nanoparticle solution, methacrylated gelatin, methacrylated polypropylene sulfide, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate, wherein the mass volume ratio of the PLX5622 nanoparticle solution, methacrylated gelatin, methacrylated polypropylene sulfide, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate is 1 mL: 40-60 mg: 15-25 mg: 4-6 mg; in the PLX5622 nanoparticle solution, the structural formula of the PLX5622 is as follows:

2. The antioxidant nanoparticle-gel preparation for targeted consumption of microglia in craniocerebral injury areas according to claim 1, characterized in that: The PLX5622 nanoparticle solution is prepared from the following raw materials in mass ratio: The structural formula of PLX5622 is shown below.

3. The antioxidant nanoparticle-gel preparation for targeted consumption of microglia in craniocerebral injury areas according to claim 2, characterized in that: The preparation method of the PLX5622 nanoparticle solution comprises the following steps: 1) Weigh lecithin, polylactic acid-glycolic acid, phospholipid-polyethylene glycol, cysteine-alanine-lysine glutamine-phospholipid-polyethylene glycol and PLX5622 according to the mass ratio; 2) Mix the above substances and dissolve them in dimethyl sulfoxide solvent, shake them in a vortex mixer to fully dissolve the components, place a centrifuge tube containing phosphate buffer solution in a heat-collecting constant temperature heating magnetic stirrer, drop the above mixture into it under stirring, and then maintain the stirring state for 1 to 3 hours to form a PLX5622 nanoparticle solution.

4. The method for preparing the antioxidant nanoparticle-gel preparation for targeted consumption of microglia in the craniocerebral injury area according to claim 1, characterized in that The steps include: 1) Weighing methacrylated gelatin, methacrylated polypropylene sulfide, lithium phenyl (2,4,6-trimethylbenzoyl) phosphate, and PLX5622 nanoparticle solution according to mass volume ratio; 2) Methacrylated gelatin, methacrylated polypropylene sulfide, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate are mixed and dissolved in a PLX5622 nanoparticle solution, and the mixture is stirred thoroughly at room temperature and protected from light to remove bubbles so that the mixture is completely dissolved into a clear liquid, thereby preparing an antioxidant nanoparticle-gel preparation that specifically consumes microglia in the craniocerebral injury area.

5. Use of the antioxidant nanoparticle-gel preparation for targeted consumption of microglia in craniocerebral injury areas as claimed in claim 1 in the preparation of a drug for treating craniocerebral trauma.

6. A compound, characterized in that Its structural formula is as follows: The compound name is methacrylated polypropylene sulfide.

7. The method for preparing the compound according to claim 6, characterized in that The steps include: 1) In a dry, nitrogen-flushed container, 1,8-diazabicyclo[5.4.0]undec-7-ene in dry tetrahydrofuran is degassed, and the temperature of the reaction mixture is lowered to 0°C, a degassed 1-butanethiol solution in tetrahydrofuran is added dropwise to the container and reacted, and then freshly distilled and degassed propylene sulfide monomer is added to the reaction mixture, and the temperature is maintained at 0°C for 1-3 hours, the reaction is quenched by adding 2-iodoethanol, and stirred at room temperature overnight, after 12 to 24 hours, the polymer solution is filtered to remove salt precipitation, and is purified by precipitation into cold methanol, and finally vacuum dried to produce a colorless viscous polymer; 2) The colorless viscous polymer of step 1) is dissolved in a mixed solution of dichloromethane and triethylamine, freshly distilled methacryloyl chloride is added dropwise at 0°C, and the reaction mixture is stirred overnight under argon. The reaction solution is transferred to a dialysis bag with a molecular weight cutoff of 2000Da, and dialyzed in pure water for 12 to 48 hours. The dialyzate is collected and freeze-dried in a freeze dryer to obtain the product methacrylated polypropylene sulfide.

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