A local long-acting anesthetic sustained-release gel and its preparation method

Abstract

This invention discloses a localized long-acting anesthetic sustained-release gel and its preparation method, belonging to the field of medical anesthetic sustained-release materials. In the preparation process, 100-300nm hollow SiO2 particles are first modified with PEG-PLA, and then emulsified using microfluidics to obtain a monodisperse suspension. Next, chitosan is dissolved, and anesthetic drugs such as lidocaine are added. The suspension is then added dropwise, and the carboxyl groups are activated using EDC-NHS, followed by a low-temperature reaction at 4°C to form a gel. This gel prolongs the drug effect through the "double drug barrier layer" of the modified hollow SiO2 particles, and its morphological stability is ensured within 24 hours by particle support. All materials are medical-grade biocompatible materials, and the microfluidic process solves particle aggregation, making it suitable for surface anesthesia.

Description

Technical Field

[0001] This invention relates to the field of medical anesthetic sustained-release materials technology, specifically disclosing a local long-acting anesthetic sustained-release gel and its preparation method. Background Technology

[0002] In the field of medical local anesthesia, local anesthetic gels are widely used in skin surface anesthesia (such as minimally invasive cosmetic procedures and epidermal puncture), mucosal anesthesia (such as dental treatment and endoscopic examination), and postoperative local analgesia due to their convenient operation, direct action on target tissues, and low systemic side effects. They are key auxiliary materials for improving patient comfort in clinical diagnosis and treatment.

[0003] Existing local anesthetic gels mostly rely on polymeric carriers to physically encapsulate drugs for sustained release. Firstly, the gel network of these carriers has a large pore size and weak drug binding force. Anesthetic drugs (such as lidocaine and ropivacaine) are easily affected by skin osmotic pressure and local fluid flow, causing rapid permeation or dissolution from the gel matrix, resulting in a short duration of anesthesia. In time-consuming procedures such as dental root canal treatment and large-area laser freckle removal, treatment needs to be interrupted multiple times to reapply the gel, not only prolonging the treatment process but also causing local irritation or interruptions in anesthetic effect due to fluctuations in drug concentration. Secondly, in clinical use, anesthetic gels need to be applied to the skin or mucous membrane surface for extended periods, often facing conditions such as sweat infiltration, body temperature influence, and slight friction (such as patient limb movement and instrument contact). Existing gel matrices, due to their low cross-linking density and lack of rigid support structure, are prone to collapse, deformation, or even rupture under these conditions, directly disrupting the pre-designed drug release channels. This may lead to a sudden increase or decrease in local drug concentration.

[0004] Hollow SiO2 particles, due to their porous structure and good mechanical properties, are often used as drug carriers and structural support agents. However, the unmodified particle surface is highly hydrophobic, making it prone to aggregation in hydrophilic chitosan gels, thus failing to perform the dual functions of sustained release and support. Therefore, it is urgent to improve the dispersibility of hollow SiO2 particles through specific modifications and combine them with chitosan gels to solve the problems of rapid release of anesthetics and easy gel collapse. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of existing local anesthetic gels, such as rapid drug release, easy morphological collapse, and poor effect of hollow SiO2 particle modifiers. It provides a local long-acting anesthetic sustained-release gel and its preparation method. By modifying hollow SiO2 particles, the "drug blocking + structural support" dual effect prolongs the release time of anesthetic drugs, while ensuring the stability of the gel morphology and avoiding collapse.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] A method for preparing a local long-acting anesthetic sustained-release gel includes the following steps:

[0008] S1. Preparation of modified hollow SiO2 particles: Take 1-2 parts by mass of hollow SiO2 particles and add them to a mixture of 20 parts by mass of anhydrous ethanol and 4 parts by mass of PEG-PLA. Disperse the mixture by ultrasonication to form a dispersed phase. At the same time, add Tween 80 to deionized water to prepare a continuous phase with a mass concentration of 0.1% for later use. Inject the dispersed phase into the dispersed phase channel of the microfluidic chip at a rate of 5 μL / min and inject the continuous phase into the continuous phase channel at a rate of 20 μL / min. Use ultrasonic assistance in the chip mixing area to form monodisperse microspheres in the continuous phase. Collect the microfluidic emulsified mixture and stir at 300 rpm for 30 minutes to obtain a uniformly dispersed PEG-PLA modified hollow SiO2 particle suspension for later use.

[0009] S2. Preparation of chitosan-anesthetic drug-modified SiO2 mixture: Add 0.5 parts by weight of chitosan to 50 parts by weight of 0.2 mM glacial acetic acid, and stir at 400 rpm for 30-40 minutes until completely dissolved to obtain chitosan (CS) solution; add 0.1-0.3 parts by weight of local anesthetic drug to CS solution, and stir for 15 minutes until the drug is completely dissolved; then slowly add the PEG-PLA modified hollow SiO2 particle suspension prepared in step S1, and continue stirring at 400 rpm for 20 minutes to obtain CS-anesthetic drug-PEG-PLA modified SiO2 mixture;

[0010] S3, Carboxyl activation and construction of crosslinking precursor: Add a deionized aqueous solution containing 0.003 parts by mass of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 0.002 parts by mass of N-hydroxysuccinimide (NHS) to the mixture in step S2, stir for 2 hours to activate the carboxyl groups (-COOH) in the chitosan molecules to form an active ester, and obtain the crosslinking precursor solution;

[0011] S4. Low-temperature reaction to form gel: The cross-linking precursor liquid from step S3 is placed in an environment of 4°C and slowly stirred at 150 rpm for 12-16 hours to allow the active chitosan ester to undergo a cross-linking reaction. At the same time, PEG-PLA-modified hollow SiO2 particles are embedded in the cross-linked gel network, ultimately obtaining a morphologically stable local long-acting anesthetic sustained-release gel.

[0012] PEG-PLA was selected as a modifier for hollow SiO2 particles. Its polyethylene glycol (PEG) segments are hydrophilic and can form hydrogen bonds with the chitosan gel matrix, improving particle dispersibility. Its polylactic acid (PLA) segments are hydrophobic and can form hydrophobic interactions with the surface of hollow SiO2 particles, enhancing the binding force between the modifier and the particles and preventing detachment during cross-linking. At the same time, the amphiphilic structure of PEG-PLA can form microcapsule structures on the particle surface, actively encapsulating anesthetic drugs and further delaying drug release.

[0013] By activating the carboxyl groups of chitosan through EDC-NHS, cross-linking between chitosan molecules is promoted to form a dense gel network. After being precisely dispersed by microfluidic emulsification, hollow SiO2 particles modified with PEG-PLA are uniformly embedded in this network. On the one hand, they support the gel structure with their own mechanical properties to prevent collapse. On the other hand, their porous structure and the microcapsule structure of PEG-PLA work together to form a "double drug barrier layer", which slows down the drug penetration rate and prolongs the anesthesia time.

[0014] In step S1, the particle size of the hollow SiO2 particles is 100-300 nm.

[0015] Hollow structures exhibit superior sustained-release properties, while solid SiO2 particles, with their higher volume, are more prone to altering the gel's state and exhibit poorer sustained-release effects. Furthermore, the smaller size of hollow SiO2 particles weakens their sustained-release effect, while larger particles are more likely to aggregate and precipitate.

[0016] In step S2, the local anesthetic drug is one of lidocaine, ropivacaine, or bupivacaine.

[0017] In step S2, the dropping rate of the PEG-PLA modified hollow SiO2 particle suspension is 1-2 mL / min to avoid excessively high local particle concentrations that could lead to aggregation.

[0018] A local long-acting anesthetic sustained-release gel was obtained using the above method.

[0019] The local long-acting anesthetic sustained-release gel can be used for local anesthesia of the skin surface. When using it, apply the gel evenly to the area to be anesthetized.

[0020] The advantages of this invention compared to the prior art are as follows:

[0021] (1) Excellent long-lasting sustained-release performance: The present invention uses PEG-PLA to modify hollow SiO2 particles. Its amphiphilic structure and porous particles work together to form a "double drug barrier layer", which prolongs the release time of anesthetic drugs, avoids multiple reapplications, and improves the ease of use.

[0022] (2) Strong morphological stability: PEG-PLA modified hollow SiO2 particles are uniformly embedded in the chitosan cross-linking network. The excellent mechanical properties of the particles support the gel structure, so that the gel remains morphologically stable within 24 hours without collapse or deformation, ensuring uniform drug release.

[0023] (3) Good biocompatibility: PEG-PLA, chitosan and hollow SiO2 particles are all medical-grade biocompatible materials, and there are no toxic reagent residues in the preparation process.

[0024] (4) High particle dispersion precision: By replacing the traditional stirring and mixing with microfluidic emulsification process, the monodispersity control of PEG-PLA modified hollow SiO2 particles is achieved. The uniform dispersion of particles in the gel solves the aggregation problem, further ensuring the uniformity of drug release and avoiding excessively strong or weak local drug effects. Attached Figure Description

[0025] Figure 1 (a) is a microscopic photograph of the gel prepared in Example 1, and (b) is a photograph of the gel prepared in Example 1.

[0026] Figure 2 (a) is a transmission electron microscope image of hollow SiO2 particles, and 2(b) is a scanning electron microscope image of modified hollow SiO2 particles.

[0027] Figure 3 These are the Fourier transform infrared spectra of Example 1 and Comparative Example 1;

[0028] Figure 4 These are comparison images of the gel morphology of Example 1 and Comparative Example 1;

[0029] Figure 5 These are the stress-tension curves of Example 1 and Comparative Example 2, with a gel photograph of Comparative Example 2 inserted.

[0030] Figure 6 This is a comparison graph of the in vitro release curves of anesthetic drugs in Example 1, Comparative Example 1, and Comparative Example 3. Detailed Implementation

[0031] To make the above-mentioned objectives, features, and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to examples. The following content is merely an example and illustration of the concept of the present invention. Those skilled in the art can make various modifications or additions to the described specific embodiments or use similar methods to replace them, as long as they do not deviate from the concept of the invention, they should all fall within the protection scope of the present invention.

[0032] The preparation method of the present invention will be described below through specific embodiments and comparative examples.

[0033] Example 1

[0034] A method for preparing a local long-acting anesthetic sustained-release gel includes the following steps:

[0035] S1. Preparation of modified hollow SiO2 particles: Take 1 part by mass of hollow SiO2 particles and add them to a mixture of 20 parts by mass of anhydrous ethanol and 4 parts by mass of PEG-PLA. Disperse the mixture by ultrasonication to form a dispersed phase. At the same time, add Tween 80 to deionized water to prepare a continuous phase with a mass concentration of 0.1% for later use. Inject the dispersed phase into the dispersed phase channel of the microfluidic chip at a rate of 5 μL / min and inject the continuous phase into the continuous phase channel at a rate of 20 μL / min. Use ultrasonic assistance in the chip mixing area to form monodisperse microspheres in the continuous phase. Collect the microfluidic emulsified mixture and stir at 300 rpm for 30 minutes to obtain a uniformly dispersed PEG-PLA modified hollow SiO2 particle suspension for later use.

[0036] S2. Preparation of chitosan-anesthetic drug-modified SiO2 mixture: 0.5 parts by mass of chitosan were added to 50 parts by mass of 0.2 mM glacial acetic acid and stirred at 400 rpm for 30 minutes until completely dissolved to obtain chitosan (CS) solution; 0.1 parts by mass of docaine were added to the CS solution and stirred for 15 minutes until the drug was completely dissolved; then the PEG-PLA modified hollow SiO2 particle suspension prepared in step S1 was slowly added dropwise at a dropping rate of 1 mL / min, and stirring was continued at 400 rpm for 20 minutes to obtain CS-anesthetic drug-PEG-PLA modified SiO2 mixture;

[0037] S3, Carboxyl activation and construction of crosslinking precursor: Add a deionized aqueous solution containing 0.003 parts by mass of EDC and NHS to the mixture in step S2, stir for 2 hours to obtain the crosslinking precursor solution;

[0038] S4. Low-temperature reaction to form gel: The cross-linking precursor liquid from step S3 is placed at 4°C and slowly stirred at 150 rpm for 12 hours to finally obtain a stable local long-acting anesthetic sustained-release gel.

[0039] In step S1, the particle size of the hollow SiO2 particles is 100-300 nm.

[0040] Example 2

[0041] A method for preparing a local long-acting anesthetic sustained-release gel includes the following steps:

[0042] S1. Preparation of modified hollow SiO2 particles: Take 1.5 parts by mass of hollow SiO2 particles and add them to a mixture of 20 parts by mass of anhydrous ethanol and 4 parts by mass of PEG-PLA. Disperse the mixture by ultrasonication to form a dispersed phase. At the same time, add Tween 80 to deionized water to prepare a continuous phase with a mass concentration of 0.1% for later use. Inject the dispersed phase into the dispersed phase channel of the microfluidic chip at a rate of 5 μL / min and inject the continuous phase into the continuous phase channel at a rate of 20 μL / min. Use ultrasonic assistance in the chip mixing area to form monodisperse microspheres in the continuous phase. Collect the microfluidic emulsified mixture and stir at 300 rpm for 30 minutes to obtain a uniformly dispersed PEG-PLA modified hollow SiO2 particle suspension for later use.

[0043] S2. Preparation of chitosan-anesthetic drug-modified SiO2 mixture: 0.5 parts by mass of chitosan were added to 50 parts by mass of 0.2 mM glacial acetic acid and stirred at 400 rpm for 30 minutes until completely dissolved to obtain a chitosan (CS) solution; 0.2 parts by mass of ropivacaine were added to the CS solution and stirred for 15 minutes until the drug was completely dissolved; then the PEG-PLA modified hollow SiO2 particle suspension prepared in step S1 was slowly added dropwise at a dropping rate of 1.5 mL / min, and stirring was continued at 400 rpm for 20 minutes to obtain a CS-anesthetic drug-PEG-PLA modified SiO2 mixture;

[0044] S3, Carboxyl activation and construction of crosslinking precursor: Add a deionized aqueous solution containing 0.003 parts by mass of EDC and NHS to the mixture in step S2, stir for 2 hours to obtain the crosslinking precursor solution;

[0045] S4. Low-temperature reaction to form gel: The cross-linking precursor liquid from step S3 is placed at 4°C and slowly stirred at 150 rpm for 12 hours to finally obtain a stable local long-acting anesthetic sustained-release gel.

[0046] In step S1, the particle size of the hollow SiO2 particles is 100-300 nm.

[0047] Example 3

[0048] A method for preparing a local long-acting anesthetic sustained-release gel includes the following steps:

[0049] S1. Preparation of modified hollow SiO2 particles: Take 2 parts by mass of hollow SiO2 particles and add them to a mixture of 20 parts by mass of anhydrous ethanol and 4 parts by mass of PEG-PLA. Disperse the mixture by ultrasonication to form a dispersed phase. At the same time, add Tween 80 to deionized water to prepare a continuous phase with a mass concentration of 0.1% for later use. Inject the dispersed phase into the dispersed phase channel of the microfluidic chip at a rate of 5 μL / min and inject the continuous phase into the continuous phase channel at a rate of 20 μL / min. Use ultrasonic assistance in the chip mixing area to form monodisperse microspheres in the continuous phase. Collect the microfluidic emulsified mixture and stir at 300 rpm for 30 minutes to obtain a uniformly dispersed PEG-PLA modified hollow SiO2 particle suspension for later use.

[0050] S2. Preparation of chitosan-anesthetic drug-modified SiO2 mixture: 0.5 parts by mass of chitosan were added to 50 parts by mass of 0.2 mM glacial acetic acid and stirred at 400 rpm for 30 minutes until completely dissolved to obtain chitosan (CS) solution; 0.3 parts by mass of bupivacaine were added to the CS solution and stirred for 15 minutes until the drug was completely dissolved; then the PEG-PLA modified hollow SiO2 particle suspension prepared in step S1 was slowly added dropwise at a dropping rate of 1.5 mL / min, and stirring was continued at 400 rpm for 20 minutes to obtain CS-anesthetic drug-PEG-PLA modified SiO2 mixture;

[0051] S3, Carboxyl activation and construction of crosslinking precursor: Add a deionized aqueous solution containing 0.003 parts by mass of EDC and NHS to the mixture in step S2, stir for 2 hours to obtain the crosslinking precursor solution;

[0052] S4. Low-temperature reaction to form gel: The cross-linking precursor liquid from step S3 is placed at 4°C and slowly stirred at 150 rpm for 12 hours to finally obtain a stable local long-acting anesthetic sustained-release gel.

[0053] In step S1, the particle size of the hollow SiO2 particles is 100-300 nm.

[0054] Comparative Example 1

[0055] A method for preparing a local long-acting anesthetic sustained-release gel includes the following steps:

[0056] S1. Preparation of chitosan-anesthetic drug mixture: Add 0.5 parts by weight of chitosan to 50 parts by weight of 0.2 mM glacial acetic acid, stir at 400 rpm for 30 minutes until completely dissolved to obtain chitosan (CS) solution; add 0.1 parts by weight of docaine to CS solution, stir for 15 minutes until the drug is completely dissolved, and continue stirring at 400 rpm for 20 minutes to obtain CS-anesthetic drug mixture;

[0057] S2, Carboxyl activation and construction of crosslinking precursor: Add a deionized aqueous solution containing 0.003 mass of EDC and NHS to the mixture in step S1, stir for 2 hours to obtain the crosslinking precursor solution;

[0058] S3. Low-temperature reaction to form gel: The cross-linking precursor liquid of step S2 is placed in an environment of 4°C and slowly stirred at 150 rpm for 12 hours to finally obtain a local long-acting anesthetic sustained-release gel.

[0059] Comparative Example 2

[0060] A method for preparing a local long-acting anesthetic sustained-release gel includes the following steps:

[0061] S1. Preparation of modified hollow SiO2 particles: Take 1 part by mass of hollow SiO2 particles, add 20 parts by mass of anhydrous ethanol, and disperse by ultrasonication to obtain a hollow SiO2 particle suspension for later use.

[0062] S2. Preparation of chitosan-anesthetic drug-modified SiO2 mixture: 0.5 parts by mass of chitosan were added to 50 parts by mass of 0.2 mM glacial acetic acid and stirred at 400 rpm for 30 minutes until completely dissolved to obtain chitosan (CS) solution; 0.1 parts by mass of docaine were added to the CS solution and stirred for 15 minutes until the drug was completely dissolved; then the hollow SiO2 particle suspension prepared in step S1 was slowly added dropwise at a dropping rate of 1 mL / min, and stirring was continued at 400 rpm for 20 minutes to obtain CS-anesthetic drug-modified SiO2 mixture;

[0063] S3, Carboxyl activation and construction of crosslinking precursor: Add a deionized aqueous solution containing 0.003 parts by mass of EDC and NHS to the mixture in step S2, stir for 2 hours to obtain the crosslinking precursor solution;

[0064] S4. Low-temperature reaction to form gel: The cross-linking precursor liquid from step S3 is placed at 4°C and slowly stirred at 150 rpm for 12 hours to finally obtain a stable local long-acting anesthetic sustained-release gel.

[0065] In step S1, the particle size of the hollow SiO2 particles is 100-300 nm.

[0066] Comparative Example 3

[0067] The difference from Example 1 is that the particle size of the hollow SiO2 particles is greater than 300 nm.

[0068] Figure 1(a) is a microscopic photograph of the gel prepared in Example 1, and (b) is a photograph of the gel prepared in Example 1. The microscopic photograph clearly shows a dense and uniform three-dimensional cross-linked network inside the gel, with PEG-PLA-modified hollow SiO2 particles uniformly embedded in the network without agglomeration. This indicates that the microfluidic emulsification process achieves precise particle dispersion, providing a structural basis for "structural support" and "uniform drug release". Figure 1 (b) is a photograph of the actual gel, which is transparent and uniform, without layering or sedimentation, and directly reflects the uniformity of the material mixing.

[0069] Figure 2 (a) is a transmission electron microscope image of hollow SiO2 particles; the transmission electron microscope shows that the unmodified particles have a hollow structure with a size between 100 and 300 nm and a smooth surface.

[0070] Figure 2 (b) is a scanning electron microscope image of the modified hollow SiO2 particles. The surface is covered with many particles, which are in a monodisperse state and do not aggregate.

[0071] Figure 3 These are the Fourier transform infrared spectra of Example 1 and Comparative Example 1;

[0072] Comparative Example 1 (without modified SiO2), Example 1 (with modified SiO2): In addition to the characteristic peaks of chitosan and lidocaine, the Si-O-Si peak of the newly added SiO2 was strongly enhanced. This proves that the modified SiO2 successfully combined with chitosan and the drug to form a stable composite system.

[0073] Figure 4 These are comparison images of the gel morphology of Example 1 and Comparative Example 1;

[0074] Comparative Example 1 (without modified SiO2): After 24 hours, the gel showed obvious deformation and edge shrinkage. Example 1 (with modified SiO2): After 24 hours, it still maintained its complete block shape without deformation. This indicates that the embedded modified SiO2 provides "rigid support" for the gel network with its excellent mechanical properties, significantly improving morphological stability.

[0075] Figure 5 These are the stress-tensile curves for Example 1 and Comparative Example 2, with the inset showing a gel photograph of Comparative Example 2. The gel fracture strength and elastic modulus of Example 1 are significantly higher than those of Comparative Example 2. This demonstrates that uniform dispersion of modified SiO2 enhances the mechanical properties of the gel (particles and the gel network work together under stress), while agglomerated unmodified particles will cluster in the gel, forming "mechanically weak points" that make the gel prone to fracture. The inset shows the gel as white, indicating the formation of large particles.

[0076] Figure 6 This is a comparison chart of the in vitro release curves of anesthetic drugs in Example 1, Comparative Example 1, and Comparative Example 3;

[0077] As can be seen, Comparative Example 1 showed the fastest drug release, while Example 1 showed the slowest drug release rate. This is because the pure chitosan network has a large pore size, allowing the drug to dissolve quickly and preventing long-term drug release.

[0078] Comparative Example 3 still showed a relatively fast release rate, and the release curve fluctuated greatly. Due to the excessively large particle size, although it could support the gel, the dispersibility was slightly poor, and the utilization rate of the porous structure was low, resulting in a weak "drug blocking" effect.

Claims

1. A method for preparing a local long-acting anesthetic sustained-release gel, characterized in that, Includes the following steps: S1. Preparation of modified hollow SiO2 particles: Hollow SiO2 particles were added to a mixture of anhydrous ethanol and PEG-PLA and ultrasonically dispersed to form a dispersed phase; Tween 80 was added to deionized water to prepare a continuous phase; the dispersed phase was injected into the dispersed phase channel of the microfluidic chip, and the continuous phase was injected into the continuous phase channel. Ultrasonic assistance was used in the chip mixing area to form monodisperse microspheres of the dispersed phase. The mixture was collected and stirred to obtain a PEG-PLA modified hollow SiO2 particle suspension. S2. Preparation of chitosan-anesthetic drug-modified SiO2 mixture: Chitosan is added to glacial acetic acid and stirred until completely dissolved to obtain a chitosan solution; local anesthetic drug is added to the chitosan solution and stirred until dissolved; the suspension from step S1 is added dropwise and stirring is continued to obtain a mixture; S3, Carboxyl activation and construction of crosslinking precursor: Add a deionized aqueous solution containing EDC and NHS to the mixture in step S2, stir, and obtain the crosslinking precursor solution; S4. Low-temperature reaction to form gel: The cross-linking precursor liquid from step S3 is placed in a low-temperature environment and slowly stirred to complete the cross-linking reaction, resulting in a local long-acting anesthetic sustained-release gel. In step S1, the amount of hollow SiO2 particles used is 1-2 parts by mass, and the particle size is 100-300nm; the amount of anhydrous ethanol used is 20 parts by mass, and the amount of PEG-PLA used is 4 parts by mass. In step S1, the mass concentration of the continuous phase is 0.1%; the injection rate of the dispersed phase is 5 μL / min, and the injection rate of the continuous phase is 20 μL / min; the stirring rate after collecting the mixture is 300 rpm, and the stirring time is 30 minutes.

2. The preparation method according to claim 1, characterized in that, In step S2, the amount of chitosan used is 0.5 parts by mass, the concentration of glacial acetic acid is 0.2 mM, and the amount used is 50 parts by mass; the stirring speed during chitosan dissolution is 400 rpm, and the stirring time is 30-40 minutes.

3. The preparation method according to claim 1, characterized in that, In step S2, the amount of local anesthetic drug used is 0.1-0.3 parts by weight, and it is one of lidocaine, ropivacaine or bupivacaine; the stirring time for drug dissolution is 15 minutes.

4. The preparation method according to claim 1, characterized in that, In step S2, the dropping rate of the PEG-PLA modified hollow SiO2 particle suspension is 1-2 mL / min; the stirring rate after dropping is 400 rpm, and the stirring time is 20 minutes.

5. The preparation method according to claim 1, characterized in that, In step S3, the amount of EDC is 0.003 parts by mass and the amount of NHS is 0.002 parts by mass; the stirring time after adding the EDC and NHS aqueous solution is 2 hours.

6. The preparation method according to claim 1, characterized in that, In step S4, the low-temperature environment temperature is 4℃; the stirring speed is 150rpm; and the stirring time is 12-16 hours.

7. A local long-acting anesthetic sustained-release gel, characterized in that, It is prepared by any one of the preparation methods described in claims 1-6.

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