An injectable long-acting selective analgesic complex and its preparation method and application

Abstract

The present invention belongs to the field of biomedicine and relates to an injectable, long-acting, selective analgesic complex, its preparation method, and application. The complex of the present invention has the properties of temperature sensitivity, injectability, and high drug loading rate. In a rat sciatic nerve block model, complete selective pain blockade can be achieved without affecting lower limb movement, and the sensory block duration is 10 times that of free local anesthetic blockade. Local tissue pathology and gross anatomy show that the complex of the present invention has good biocompatibility and degradability, and is a long-acting, sustained-release, selective pain-blocking local anesthetic biomaterial preparation with potential for clinical translation.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine and relates to an injectable long-acting selective analgesic compound and a preparation method and application thereof. Background Art

[0002] Sensorimotor dissociative analgesia involves the selective blockade of sensory nerves by local anesthetics, achieving analgesia while preserving limb motor function. Currently, only low-concentration ropivacaine can achieve this in clinical practice. Dissociative anesthesia is widely used for perioperative and postoperative analgesia, particularly in low-spine surgery, labor analgesia, and orthopedic lower limb surgery. It facilitates timely intraoperative assessment of lower limb motor status, avoids spinal nerve damage during surgical procedures, and reduces the use of systemic sedatives and analgesics. Furthermore, indwelling postoperative nerve block analgesia pumps can effectively relieve postoperative pain, improve patient satisfaction, and promote rapid postoperative recovery. However, while previously reported local anesthetic biomaterial systems can prolong local anesthetic blockade to a certain extent, they still suffer from limitations such as relatively complex preparation techniques, inability to achieve minimally invasive drug delivery, and lack of selective pain blockade. To address the current challenges of local anesthetic blockade analgesia and improve its efficacy, the development of novel local anesthetic formulations with long-acting sustained release and selective pain blockade is urgently needed. The research and development of new local anesthetic biomaterial preparations is expected to achieve the goal of prolonging the duration of action of local anesthetics and achieving complete selective pain blockade after a single minimally invasive administration without increasing the toxic and side effects of local anesthetics, thereby solving the current problems of local anesthetic block analgesia, improving local analgesia effects, and promoting rapid recovery of patients.

[0003] Electrospinning drug delivery systems offer unique advantages, including high drug delivery efficiency, low burst release, long drug release cycles, and controllable release behavior. However, due to their solid and fragile structure, traditional electrospinning is typically implanted at the site of action through open surgery, making minimally invasive drug delivery difficult. Injectable hydrogels loaded with drugs exhibit a sustained-release effect. After injection, the hydrogel rapidly gels at the target site while maintaining sufficient strength and integrity, facilitating localized drug action and minimizing drug diffusion and systemic effects.

[0004] However, the prior art still lacks a composite material with good injectability, long-acting sustained release, and selective pain blocking. Summary of the Invention

[0005] The present invention aims to overcome at least one of the above-mentioned shortcomings of the prior art, combine the advantages of hydrogel and electrospinning, increase the lubricity of electrospinning through the lubricating effect of hydrogel, and construct an injectable electrospinning-hydrogel sustained-release material loaded with local anesthetic.

[0006] In one aspect, the present invention provides a method for preparing an electrospinning-hydrogel composite, comprising the following steps:

[0007] S1. Preparing electrospun fibers loaded with local anesthetics, wherein the mass ratio of polymer material to local anesthetic is (1-5):1;

[0008] S2. The electrospun fibers prepared in step S1 are cut into short fibers having a length of 10-100 μm;

[0009] S3. Preparation of hydrogel loaded with TRPV1 receptor agonist;

[0010] S4. The short-spinning fibers prepared in step S2 and the hydrogel loaded with the TRPV1 receptor agonist prepared in step S3 are mixed to prepare an electrospinning-hydrogel composite.

[0011] TRPV1 channels mediate the entry of local anesthetics into sensory neurons, exerting a specific pain-blocking effect. TRPV1 receptor agonists can activate this channel, thereby mediating the entry of local anesthetics.

[0012] In some embodiments, the mass ratio of the polymer material to the local anesthetic is 1:1, 2:1, 3:1, 4:1, or 5:1.

[0013] In some embodiments, the electrospun filaments prepared in step S1 are cut into short filaments with a length of 10-90 μm; in some embodiments, the electrospun filaments prepared in step S1 are cut into short filaments with a length of 12-75 μm; in some embodiments, the electrospun filaments prepared in step S1 are cut into short filaments with a length of 18-30 μm; in some embodiments, the electrospun filaments prepared in step S1 are cut into short filaments with a length of 15-25 μm; in some embodiments, the electrospun filaments prepared in step S1 are cut into short filaments with a length of 20, 40, 60, 80 or 100 μm.

[0014] In some embodiments, step S1 comprises the following steps:

[0015] S11. Adding the polymer material and the local anesthetic to a solvent and fully dissolving them to prepare an electrospinning solution; preferably, the solvent is selected from dichloromethane (DCM) or hexafluoroisopropanol (HFIP);

[0016] S12. The electrospinning solution prepared in S11 was transferred to a syringe for electrospinning. The electrospinning parameters included: spinning solution injection rate: 1.00-1.20 mL / h; distance between the syringe needle and the roller collector: 8-12 cm; rotating roller collector speed: 420-480 rpm; electrostatic field voltage: 8-16 kV;

[0017] S13. After the electrospinning in S12 is completed, remove the electrospun fiber membrane from the roller and dry it to remove the solvent.

[0018] In some embodiments, in step S2, the electrospun fibers prepared in step S1 are cut using a freezing cutting method.

[0019] In some embodiments, step S3 comprises the following steps:

[0020] S31. The gelling agent is added to ddH2O to prepare a sol solution having a mass fraction of 30%-50%;

[0021] S32. The sol solution prepared in step S31 is stirred and placed in a -80 to -40 ° C refrigerator for 3-8 min;

[0022] S33. After removing the sol solution of step S32, repeat step S32 1-3 times;

[0023] S34. Remove the sol solution from step S33 to obtain a fully dissolved sol solution;

[0024] S35. The TRPV1 receptor agonist is dissolved in a solvent to prepare a TRPV1 receptor agonist mother solution; preferably, the solvent is DMSO;

[0025] S36. The sol solution prepared in step S34 and the TRPV1 receptor agonist mother solution prepared in step S35 are fully mixed to obtain a hydrogel loaded with TRPV1 receptor agonist.

[0026] In some embodiments, step S4 comprises the following steps:

[0027] The short-spinning prepared in step S2 and the hydrogel loaded with TRPV1 receptor agonist prepared in step S3 are fully mixed according to the mass ratio of local anesthetic to TRPV1 receptor agonist in the electrospinning-hydrogel composite being 10:1 to obtain an electrospinning-hydrogel composite loaded with local anesthetic and TRPV1 receptor agonist.

[0028] In some embodiments, the polymer material is selected from any one or more of polycaprolactone, polylactic acid-co-glycolic acid, and polylactic acid; in some embodiments, the local anesthetic is selected from lidocaine or a pharmaceutically acceptable salt thereof or a derivative thereof; preferably, the lidocaine derivative is lidocaine N-bromoethane; in some embodiments, the TRPV1 receptor agonist is selected from the following drugs or pharmaceutically acceptable salts thereof: capsaicin, resiniferatoxin, olvanil, arvanil, SDZ-249665, SDZ-249482, nuvanil, and capsavanil.

[0029] In some embodiments, the gelling agent is selected from one or more of carrageenan, xanthan gum, sodium alginate, methylcellulose, polyvinyl pyrrolidone, polyacrylic acid resin, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, carbomer, poloxamer and sodium carboxymethyl cellulose; in some embodiments, the poloxamer is poloxamer F127.

[0030] In one aspect, the present invention provides an electrospinning-hydrogel composite prepared by the method.

[0031] In one aspect, the present invention provides a dual-drug electrospinning-hydrogel composite comprising:

[0032] a. electrospinning loaded with a local anesthetic, wherein the mass ratio of the polymer material and the local anesthetic is (1-5): 1; and

[0033] b. Hydrogel loaded with TRPV1 receptor agonist.

[0034] In one aspect, the present invention provides the use of the electrospinning-hydrogel composite in the preparation of selective analgesic drugs.

[0035] In some embodiments, the present invention uses electrospinning technology to prepare polycaprolactone (PCL) loaded with lidocaine N-bromoethane (N-Ethyllidocaine bromide, QX-314) electrospun fibers, and prepares Fiber-QX314 short spinning fibers by freeze cutting method; and uses physical mixing method to prepare poloxamer F127 (capsaicin, Cap) loaded with capsaicin. F127) hydrogel; then, the mixture was mixed in appropriate proportions to produce an injectable Fiber-QX314 / Gel-Cap electrospun-gel composite. The analgesic efficacy of the composite was investigated in a rat sciatic nerve block model, and its in vivo biosafety and biodegradability were verified.

[0036] The electrospinning-hydrogel composite of the present invention can be administered through minimally invasive injection, while reducing the systemic toxic side effects of local anesthetics, achieving long-lasting sustained release and completely selective pain blocking effects, thereby achieving "walkable" regional block analgesia, promoting postoperative recovery of patients, and having good transformation application prospects. In the rat sciatic nerve block model, complete selective pain blocking can be achieved without affecting the movement of the lower limbs. The sensory block time is up to 44.0 hours, which is 10 times the block time of free local anesthetics, indicating that the composite has a complete sensory and motor separation analgesic effect. Local tissue pathology and gross anatomy show that the electrospinning-hydrogel drug-loaded composite of the present invention has good biocompatibility and degradability. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 Schematic diagram of preparing Fiber-QX314 short spinning by freeze cutting method.

[0038] Figure 2 Synthesis of electrospinning-gel composite: (A) Fiber-QX314 short spinning; (B) Gel-Cap hydrogel; (C) Fiber-QX314 / Gel-Cap electrospinning-gel composite.

[0039] Figure 3 The morphology of the electrospun-gel composite under a scanning electron microscope (Scale bar = 10 μm).

[0040] Figure 4 Thermosensitivity of electrospinning-gel composite.

[0041] Figure 5 The injectability of electrospun-gel composites.

[0042] Figure 6 In vivo safety of electrospinning-gel composite drugs (Scale bar = 200 μm).

[0043] Figure 7 In vivo degradation of electrospun-gel composite drug: the blue arrow indicates the sciatic nerve, and the red arrow indicates the residual material in the body. DETAILED DESCRIPTION

[0044] The following is a detailed description of the technical solution of the present invention, which does not limit the scope of protection of the present invention. Non-essential modifications and adjustments made by others based on the concept of the present invention still fall within the scope of protection of the present invention.

[0045] Raw materials and equipment

[0046] Raw materials: polycaprolactone (PCL, [η] = 1.8 ± 0.2 dL / g), poloxamer F127 ( F127, molecular weight MW = 12600), lidocaine N-bromoethane (QX-314), and capsaicin (Cap) were purchased from China Macklin Company.

[0047] Equipment: electrospinning apparatus, magnetic stirrer, freezing microtome, constant temperature shaker, vacuum drying oven.

[0048] Example 1 Synthesis of electrospun fibers loaded with QX-314 (Fiber-QX314)

[0049] Different drug-loaded electrospinning fibers were prepared according to different polymer materials, electrospinning parameters, and different ratios of polymer materials to QX-314 as shown in Table 1.

[0050] Table 1 Ratio of electrospun drug-loaded fibers

[0051]

[0052] *Note: The electrospinning formula is expressed as: a% polymer:QX-314 (x:y). This means the electrospinning formula contains a% (w / w) polymer, and the weight ratio (w / w) of polymer to QX-314 is x:y. PLGA: poly(lactic-co-glycolic acid); PLA: polylactic acid.

[0053] **Note: DCM: dichloromethane; HFIP: hexafluoroisopropanol.

[0054] The preparation method comprises:

[0055] (1) Weigh 200 mg of polymer material and lidocaine N-bromoethane (QX-314), add them to the solvent in sequence, and stir them magnetically at room temperature for 2 h to fully dissolve them. Prepare a Fiber-QX314 electrospinning solution containing the corresponding w / w ratio of polymer material and QX-314.

[0056] (2) The electrospinning solution from step (1) was transferred into a 2.5 mL syringe containing a uniaxial 25G stainless steel needle.

[0057] (3) Electrospinning Parameters: The voltage, rotating roller collector speed, and distance between the needle and the roller collector were set according to the parameters in Table 1. The spinning solution was spun at a jet speed. The electrospun fibers were prepared under the environmental conditions of 24 ± 0.5°C and 40 ± 5% humidity.

[0058] (4) After the spinning is completed, the electrospun fiber membrane is completely removed from the roller, spread flat on tin foil, and vacuum dried overnight to further remove the organic solvent.

[0059] (5) The next day, take out the dried electrospun membrane and store it in a drying cabinet for future use.

[0060] The prepared electrospun drug-loaded fibers were tested for performance, including stability, injectability, and drug release duration.

[0061] Stability: In step (3), if a stable spinning Taylor cone is formed after injection, it indicates that the spinning is stable.

[0062] Injectability: The injectability of the Fiber-QX314 / Gel-Cap electrospun-gel composite was evaluated using an in vitro injection test. A test tube containing the electrospun-gel composite solution was placed in an ice box. A 2.5 mL syringe was used to draw a certain amount of solution. Injection was attempted using needles with diameters of 0.8, 1, 1.2, and 1.5 mm. The ability of the composite solution to pass through the needle without resistance was observed to determine the composite's injectability.

[0063] Drug Release Duration: To investigate the release pattern and sustained-release duration of the drug from the composite material, a 7-day drug release test was conducted. Since the UV absorption peaks of the two drugs, QX-314 and Cap, are similar, separate release tests were performed to avoid interference during measurement.

[0064] (1) 1 mL of Fiber-QX314 / Gel (containing 10 mg of QX-314) or Fiber / Gel-Cap (containing 1 mg of Cap) complex solution was placed in dialysis bags (MWCO = 3500 Da), sealed, and then placed in 20 mL sample bottles (n = 3 / group).

[0065] (2) The sample bottle was transferred to a 37°C constant temperature water bath for 10 minutes to form a colloidal spinning-gel composite material.

[0066] (3) Add 15 mL of PBS buffer to the sample bottle, ensuring that the buffer submerges the dialysis bag.

[0067] (4) Transfer the sample bottle to a 37°C constant temperature shaking incubator and incubate at a speed of 40 r / min.

[0068] (5) At the predetermined time points (0, 0.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and 168 h), 300 μL of dialysate was aspirated and reserved for testing. After each aspiration, 300 μL of fresh PBS buffer was added.

[0069] (6) Using an ultraviolet spectrophotometer, measure the absorbance values ​​of QX-314 and Cap in the dialysis solution at each time period at 262 nm and 280 nm, respectively.

[0070] (7) Based on the standard curves of QX-314 and Cap, the concentrations of QX-314 and Cap in all tested samples were calculated, and the cumulative drug release was calculated.

[0071] The properties of different electrospun drug-loaded fibers in Table 1 are shown in Table 2:

[0072] Table 2 Properties of different electrospun drug-loaded fibers in Table 1

[0073]

[0074] Comparing the properties and drug release duration of each electrospun fabric, we found that the 20% PCL:20% QX-314 fabric had a higher drug loading rate than the 20% PCL:10% QX-314 fabric. However, the 10% PLGA:10% QX-314 fabric was stiffer than the 20% PCL:20% QX-314 fabric, making it less suitable for subsequent cutting and injection experiments. Therefore, we ultimately chose to synthesize a stable, drug-loaded PCL electrospun fabric (20% PCL:20% QX-314) with sustained release for up to 96 hours.

[0075] Example 2 Preparation of Fiber-QX314 Short Spinning by Freezing Cutting Method

[0076] After repeated attempts, the Fiber-QX314 electrospun fibers synthesized in Example 1 were relatively tough, but difficult to achieve injectability. The Fiber-QX314 electrospun membrane (20% PCL: 20% QX-314) was further cut into regular short spinning fibers using the freeze-cutting method. The specific steps are as follows:

[0077] (1) The dried Fiber-QX314 electrospun membrane was cut into rectangular membrane pieces of 1 cm × 2 cm in size.

[0078] (2) Place the small pieces of electrospun membrane neatly into an ice-cut mold with a length × width × height of 1 cm × 2 cm × 1 cm, ensuring that the spinning long axis direction of the electrospun membrane is consistent.

[0079] (3) Add an appropriate amount of ddH2O into the mold and ensure that the electrospun membrane is completely immersed, and immediately transfer the mold to a -80℃ freezer for freezing and fixation.

[0080] (4) After 1 hour, remove the frozen mold and immediately transfer it to a freezing ice cutter (the temperature inside the box is adjusted to -20°C).

[0081] (5) Freeze cutting: The direction of the electrospun membrane is perpendicular to the cutting direction, and then the electrospun membrane embedded in water is cut regularly with a cutting thickness of 20-100 μm.

[0082] (6) All the short fibers of regular length after cutting were collected and freeze-dried for 24 h to obtain Fiber-QX314 short fibers with a length of 20-100 μm.

[0083] The injectability and cumulative drug release duration of Fiber-QX314 short-spin fibers with cutting lengths of uncut, 20 μm, 40 μm, 60 μm, 80 μm, and 100 μm were compared to determine the appropriate cutting length.

[0084] The spinning performance tests were carried out on the fibers with different cutting lengths. The specific method was the same as 1). The results are shown in Table 3.

[0085] Table 3 Performance comparison of Fiber-QX314 short spinning with different cutting lengths

[0086]

[0087] The cumulative drug release time of short spinning with a cutting length of 20μm and 40μm was as long as 96h, and there was no statistical difference between the two; but in the injectability experiment, it was found that the longer the spinning length, the greater the injection resistance. In order to ensure the injectability of spinning, the 20μm length was finally determined for subsequent experiments.

[0088] The drug loading capacity (DLC) and encapsulation efficiency (DLE) of 20 μm Fiber-QX314 short-spin fibers were determined: 10 mg of Fiber-QX314 short-spin fibers were dissolved in 200 μl of dichloromethane (DCM), and the absorbance of QX-314 at 262 nm was detected by UV spectrophotometer and the mass of QX-314 was calculated.

[0089] The DLC and DLE calculation formulas of QX-314 are as follows: DLC (%) = (QX-314 mass) / (total fiber mass) × 100%; DLE (%) = (QX-314 mass) / (initial drug input mass) × 100%.

[0090] The drug loading rate of 20 μm Fiber-QX314 short-spin fibers was as high as 39.2±0.5%, and the encapsulation efficiency was 78.3±0.9%.

[0091] Example 3 Synthesis of Capsaicin-Loaded Hydrogel (Gel-Cap)

[0092] (1) Weigh a certain mass F127 (F127) powder was added to a 50 mL centrifuge tube containing ddH2O to prepare an F127 sol solution with a mass fraction concentration of 40%.

[0093] (2) Stir manually with a glass rod for at least 20 minutes to fully dissolve the F127 powder.

[0094] (3) Place the stirred solution in a -80°C refrigerator for 5 min to further dissolve the F127 sol.

[0095] (4) Take out the F127 sol solution, stir it manually for 10 minutes again, and then put it into a -80℃ refrigerator for 5 minutes to obtain a fully dissolved F127 sol solution. Then put it into a 4℃ refrigerator for storage.

[0096] (5) Preparation of Gel-Cap Hydrogel: Weigh a certain amount of capsaicin (Cap) and dissolve it in dimethyl sulfoxide (DMSO) to prepare a 20 mg / mL Cap stock solution. A certain volume of Cap solution and F127 sol solution were mixed thoroughly by vortexing at 4°C and then allowed to stand at room temperature for 2 min to obtain Cap-loaded F127 hydrogel.

[0097] Example 4 Preparation of electrospinning-hydrogel composite loaded with QX-314 and capsaicin

[0098] (1) Based on the drug loading of the Fiber-QX314 electrospun membrane calculated in Example 2, a Fiber-QX314 electrospun membrane containing 15 mg of QX-314 was weighed.

[0099] (2) Weigh a certain amount of Cap and dissolve it in DMSO to prepare a 15 mg / mL Cap solution. Take a certain volume of Cap solution and 40% F127 sol, vortex thoroughly at 4°C to prepare an F127 sol containing 1.5 mg / mL Cap.

[0100] (3) The composite material was prepared with a mass ratio of QX-314 to Cap of 10:1. The Fiber-QX314 electrospun membrane containing 15 mg of QX-314 and 1 mL of F127 sol containing 1.5 mg of Cap were thoroughly vortexed at 4°C to obtain the Fiber-QX314 / Gel-Cap electrospun-gel composite. Figure 2 shown.

[0101] Example 5 Characterization of electrospun hydrogel composite loaded with QX-314 and capsaicin

[0102] Scanning electron microscopy (SEM) was used to observe the surface morphology of electrospun fibers and electrospun-gel composites. Figure 3 ), SEM showed that the electrospun fibers loaded with QX-314 were thinner than those without drug-loaded PCL, and the electrospun fibers were evenly distributed in the sericin composite, while finer fibers were more conducive to achieving injectability.

[0103] The simple test tube inversion method was used to measure that the Fiber-QX314 / Gel-Cap composite material can form a gel state at 37°C and return to a flowable sol state at 4°C, which shows that the composite has temperature-sensitive properties ( Figure 4 ).

[0104] In vitro injectability experiments showed that the complex could pass through an injection needle with a diameter of 1.2 mm, indicating that the complex was injectable ( Figure 5 ).

[0105] Example 6 In vivo blocking effect of electrospun hydrogel composite loaded with QX-314 and capsaicin

[0106] Rat sciatic nerve block model: The rat was placed in lateral recumbency, with the femur and trunk forming a right angle. The ischial tuberosity and greater trochanter were palpated and the injection needle was directed along the posterior middle third of the greater trochanter along the trunk. The material was injected around the sciatic nerve of one lower limb, and the sensory and motor block effects of the lower limb were observed.

[0107] Evaluation of Drug Blockade Efficacy: Twenty-four male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n=6 / group): Saline, QX-314+Cap, Fiber / Gel, and Fiber-QX314 / Gel-Cap. Each rat was injected with 1 mL of drug around the left sciatic nerve to establish a sciatic nerve block model. The motor and sensory blockade efficacy of the sciatic nerve was assessed using the motor block four-point scale and mechanical paw withdrawal pain threshold.

[0108] The results showed that compared with the free drug QX-314+Cap group, the Fiber-QX314 / Gel-Cap composite group significantly prolonged the duration of sciatic nerve sensory block in rats (3.7±0.6h vs 44.0±4.0h). In addition, the Fiber-QX314 / Gel-Cap composite group did not affect the rats' lower limb movements, indicating that the composite has a completely selective pain blockade effect, namely, a sensorimotor dissociative analgesia effect (Table 4).

[0109] Table 4 Evaluation of drug blocking effect in vivo of electrospinning-gel composites

[0110]

[0111] Example 7 In vivo blocking effect of electrospun hydrogel composite loaded with QX-314 and capsaicin

[0112] To further evaluate the safety and biodegradability of the composite drug material in vivo, rats were sacrificed 7 days after administration, and multiple organs were removed for HE staining to investigate the biocompatibility of the material. Local gross dissections were performed 7 and 21 days after administration to observe material degradation.

[0113] The results showed that compared with the Saline group, the Fiber-QX314 / Gel-Cap material group did not damage organ tissues ( Figure 6 ), and the composite material had been initially degraded on the 7th day and was completely degraded on the 21st day ( Figure 7 ), the results showed that the composite material has good biocompatibility and degradability in vivo.

Claims

1. A method for preparing an electrospinning-hydrogel composite, characterized in that: The following steps are involved: S1. preparing electrospun fibers loaded with local anesthetics, wherein the mass ratio of polymer material to local anesthetic is (1-5):1; S2. The electrospun fibers prepared in step S1 are cut into short fibers having a length of 10-40 μm; S3. Preparation of hydrogel loaded with TRPV1 receptor agonist; S4. The short-spinning prepared in step S2 and the hydrogel loaded with the TRPV1 receptor agonist prepared in step S3 are mixed to prepare an electrospinning-hydrogel composite; The polymer material is selected from polycaprolactone; The local anesthetic is selected from lidocaine N-bromide; The TRPV1 receptor agonist is selected from one of the following drugs or pharmaceutically acceptable salts thereof: capsaicin, resiniferatoxin, olvanil, arvanil, SDZ-249665 and nuvanil.

2. The preparation method according to claim 1, wherein The step S1 comprises the following steps: Step S11. Adding the polymer material and the local anesthetic into a solvent and fully dissolving them to prepare an electrospinning solution; the solvent is selected from dichloromethane or hexafluoroisopropanol; Step S12. Transferring the electrospinning solution prepared in S11 to a syringe for electrospinning. The electrospinning parameters include: a spinning solution injection rate of 1.00-1.20 mL / h; a distance between the syringe needle and the roller collector of 8-12 cm; a rotating roller collector speed of 420-480 rpm; and an electrostatic field voltage of 8-16 kV. Step S13: After the electrospinning is completed, the electrospun fiber membrane is removed from the roller and dried to remove the solvent.

3. The preparation method according to claim 1, wherein In the step S2, the electrospun fibers prepared in the step S1 are cut using a freezing cutting method.

4. The preparation method according to claim 1, wherein The step S3 comprises the following steps: S31. The gelling agent is added to ddH2O to prepare a sol solution having a mass fraction of 30%-50%; S32. The sol solution prepared in step S31 is stirred and placed in a -80 to -40 ° C refrigerator for 3-8 min; S33. After removing the sol solution of step S32, repeat step S32 1-3 times; S34. Remove the sol solution from step S33 to obtain a fully dissolved sol solution; S35. The TRPV1 receptor agonist is dissolved in a solvent to prepare a TRPV1 receptor agonist mother solution; the solvent is DMSO; S36. The sol solution prepared in step S34 and the TRPV1 receptor agonist mother solution prepared in step S35 are fully mixed to obtain a hydrogel loaded with TRPV1 receptor agonist.

5. The preparation method according to claim 1, wherein The step S4 comprises the following steps: The short-spinning prepared in step S2 and the hydrogel loaded with TRPV1 receptor agonist prepared in step S3 are fully mixed according to the mass ratio of local anesthetic to TRPV1 receptor agonist in the electrospinning-hydrogel composite being 10:1 to obtain an electrospinning-hydrogel composite loaded with local anesthetic and TRPV1 receptor agonist.

6. The preparation method according to claim 4, wherein The gelling agent is selected from one or more of carrageenan, xanthan gum, sodium alginate, methylcellulose, polyvinyl pyrrolidone, polyacrylic acid resin, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, carbomer, poloxamer and sodium carboxymethylcellulose; The poloxamer is poloxamer F127.

7. An electrospinning-hydrogel composite prepared by the preparation method according to any one of claims 1 to 6.

8. Use of the electrospinning-hydrogel composite according to claim 7 in the preparation of a selective analgesic drug.

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