A composite material containing a local anesthetic drug and a method for preparing the same
By preparing a composite material containing bupivacaine hydrochloride, a photothermal conversion agent, and a penetration enhancer, the pain and toxic side effects caused by frequent administration of local anesthetics were resolved, achieving local on-demand release and rapid analgesia.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- THE PEOPLES HOSPITAL WEIFANG CITY CN0
- Filing Date
- 2026-02-28
- Publication Date
- 2026-06-09
AI Technical Summary
Existing local anesthetics, when used frequently to treat postoperative infections, cause pain and toxic side effects, and the heat pain from photothermal therapy affects the treatment outcome.
A composite material containing bupivacaine hydrochloride, a photothermal conversion agent, δ-juniperene, and a penetration enhancer is used. By combining the photothermal conversion agent and bupivacaine hydrochloride with a penetration enhancer composed of egg membrane protein peptides and polylysine, local on-demand release and rapid pain relief can be achieved.
It alleviated the discomfort caused by photothermal therapy, prolonged the analgesic time, avoided the pain and toxic side effects caused by frequent dressing changes, and improved the local anesthetic effect.
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Figure CN122163789A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biotechnology and pharmaceutical technology, and in particular relates to a composite material containing a local anesthetic drug and its preparation method. Background Technology
[0002] Postoperative bacterial infections are prevalent, especially those caused by drug-resistant bacteria, which reduces the effectiveness of traditional antibiotics. Severe infections can threaten patients' lives, and the pain during prolonged treatment can affect their prognosis. Photothermal therapy utilizes photothermal conversion to raise the temperature at the infection site, rapidly killing antibacterial activity and offering the advantage of not inducing drug resistance. However, the treatment involves high-energy laser irradiation, and the heat generated can cause pain, leading patients to scratch the wound, causing dressings to fall off and affecting treatment.
[0003] Local anesthetics are among the most effective drugs currently used in clinical practice for pain management. They offer advantages such as surface infiltration for analgesia and anti-inflammation, reducing the limitations of systemic medication and minimizing side effects. Bupivacaine (BU) has antibacterial and anti-inflammatory effects and has shown significant advantages in treating infected wounds. However, to maintain therapeutic efficacy, frequent administration of small doses is often required, which not only causes pain and burden for patients but also leads to toxic side effects due to the accumulation of drug concentrations in the blood. Therefore, there is an urgent need to develop a controllable drug delivery system to achieve on-demand release of local anesthetics, improve their penetration into wounds, prolong the duration of action, and produce a local anesthetic effect. Summary of the Invention
[0004] To overcome the shortcomings of existing technologies, one objective of this invention is to provide a composite material containing a local anesthetic drug. This composite material exhibits good biocompatibility. By adding a photothermal conversion agent and bupivacaine hydrochloride, it alleviates discomfort associated with photothermal therapy. The combination of δ-juniperene and bupivacaine hydrochloride can improve analgesia while reducing the dosage of bupivacaine hydrochloride, prolonging the duration of analgesia, avoiding the pain caused by frequent dressing changes, and mitigating the toxic side effects resulting from the accumulation of drug concentration in the blood. Furthermore, the addition of a penetration enhancer composed of egg membrane protein peptides and polylysine promotes the absorption of the active ingredient through the skin, rapidly exerting an analgesic effect.
[0005] The second objective of this invention is to provide a method for preparing a composite material containing a local anesthetic drug.
[0006] One of the objectives of this invention is achieved through the following technical solution:
[0007] A composite material containing a local anesthetic drug comprises the following raw materials in parts by weight: 10-15 parts bupivacaine hydrochloride, 4-8 parts photothermal conversion agent, 0.5-1 part δ-juniperene, 1-3 parts penetration enhancer, and 2-5 parts glycerin.
[0008] Furthermore, the penetration enhancer is composed of egg membrane protein peptides and polylysine in a mass ratio of 1:(1-3).
[0009] Further, the preparation process of the photothermal conversion agent is as follows: 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin and 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) are added to a solvent and heated to react, thereby obtaining the photothermal conversion agent.
[0010] Further, the molar ratio of 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin, 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) is 1:(2-8); the solvent is dimethyl sulfoxide; the amount ratio of 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) to dimethyl sulfoxide is 1 mmol:4-6 mL.
[0011] Furthermore, the chemical structural formula of the 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin is as follows:
[0012] The chemical structural formula of 3,3'-((1E,1'E)-(ethane-1,2-dimethylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) is as follows:
[0013] .
[0014] Furthermore, the reaction is carried out at a temperature of 175-185°C for a time of 35-45 hours.
[0015] Furthermore, the preparation process of the egg membrane protein peptide is as follows:
[0016] (1) Take raw eggshells, soak them in an acidic solution, remove the egg membrane, wash the egg membrane, dry it, and crush it to obtain egg membrane powder;
[0017] (2) Add the egg membrane powder obtained in step (1) to the mixture and hydrolyze it;
[0018] (3) Adjust the pH value of the system after hydrolysis in step (2), add alkaline protease for enzymatic hydrolysis, centrifuge after enzyme inactivation, take the supernatant for ultrafiltration, collect the retentate, freeze dry and sterilize to obtain the final product.
[0019] Further, the mass of the acidic solution in step (1) is 4-6 times that of the raw eggshell; the acidic solution is a phosphoric acid solution with a concentration of 0.8-1.2 mol / L; the soaking temperature is 0-4℃ and the soaking time is 2-3 days.
[0020] Further, in step (2), the ratio of egg membrane powder to the mixture is 1g:(10-15)mL; the mixture is composed of sodium hydroxide solution and anhydrous ethanol in a volume ratio of (6-9):1, the concentration of the sodium hydroxide solution is 0.5-1mol / L; the hydrolysis temperature is 50-55℃ and the time is 1-2h.
[0021] Further, the pH value of the system described in step (3) is 9-11; the amount of alkaline protease used is (2-4)×10. 5 U / mL; the enzymatic hydrolysis temperature is 55-65℃, and the time is 3-5h.
[0022] The second objective of this invention is achieved by the following technical solution:
[0023] A method for preparing a composite material containing a local anesthetic drug includes the following steps: mixing bupivacaine hydrochloride, a photothermal conversion agent, δ-juniperene, a penetration enhancer, and glycerin evenly according to the specified ratio to obtain the final product.
[0024] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0025] 1. This invention provides a composite material containing a local anesthetic drug, composed of bupivacaine hydrochloride, a photothermal conversion agent, δ-juniperene, and a penetration enhancer. By adding the photothermal conversion agent and bupivacaine hydrochloride, the discomfort caused by photothermal therapy is alleviated. The combination of δ-juniperene and bupivacaine hydrochloride can improve the analgesic effect and prolong the analgesic time while reducing the dosage of bupivacaine hydrochloride, avoiding the pain caused by frequent dressing changes and the toxic side effects caused by the accumulation of blood drug concentrations. This invention adds a penetration enhancer composed of egg membrane protein peptides and polylysine to further promote the absorption of the active ingredient by the skin, rapidly exerting an analgesic effect.
[0026] 2. The composite material of the present invention has good biocompatibility and can be released on demand during photothermal therapy, solving the problem of short duration of action and frequent use of local anesthetics.
[0027] 3. The present invention provides a method for preparing the above-mentioned composite material, which is simple and easy to operate. Attached Figure Description
[0028] Figure 1 This is the infrared spectrum of the photothermal conversion agent of the present invention. Detailed Implementation
[0029] The present invention will now be further described with reference to the accompanying drawings and specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, all reagents or instruments used are conventional products obtained through commercial channels.
[0030] The preparation process of 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) of this invention is as follows: 2 mmol of 4-hydroxyisophthalaldehyde and 1 mmol of ethylenediamine were dissolved in 20 mL of methanol, refluxed at 50 °C for 40 min, filtered, washed three times with methanol, and dried under vacuum at 80 °C to obtain the ligand; then, under Ar2 atmosphere, 1 mol of the ligand and 1 mol of ferrous acetate were added to 20 mL of methanol and stirred for 24 h. After the reaction was completed, the mixture was filtered, washed with methanol, and dried to obtain 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II); its chemical structural formula is as follows: .
[0031] The preparation process of 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin of this invention is as follows: 5,10,15,20-tetrakis(4-cyanophenyl)porphyrin (1.23 mmol), dicyandiamide (6.15 mmol), and KOH (7.95 mmol) were mixed, degassed, and purged with argon. Dry 2-methoxyethanol (30 mL) was then added to the reaction system; the mixture was refluxed at 110 °C for 48 h. The product was washed with distilled water and dried to obtain 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin; its chemical structural formula is as follows: .
[0032] Example 1
[0033] A composite material containing a local anesthetic drug comprises the following raw materials in parts by weight: 13 parts bupivacaine hydrochloride, 6 parts photothermal conversion agent, 0.8 parts δ-juniperene, 2 parts penetration enhancer, and 3 parts glycerin;
[0034] The penetration enhancer is composed of egg membrane protein peptides and polylysine in a mass ratio of 1:2.
[0035] The preparation process of the photothermal conversion agent is as follows:
[0036] 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin and 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) were added to dimethyl sulfoxide at a molar ratio of 1:8. The amount of 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) and dimethyl sulfoxide was 1 mmol: 4 mL. The reaction was carried out at 180 °C for 42 h. After the reaction was completed, the reaction solution was cooled to room temperature, filtered, and washed with methanol, DMF, and TFH until the filtrate was colorless. After drying, the photothermal conversion agent was obtained.
[0037] The preparation process of egg membrane protein peptides is as follows:
[0038] (1) Take raw eggshells, clean them, add them to a 1 mol / L phosphoric acid solution, the mass of the phosphoric acid solution is 5 times that of the raw eggshells, soak them at 0℃ for 2 days, take out the egg membrane, wash the egg membrane, dry it, crush it and pass it through a 100-mesh sieve to obtain egg membrane powder.
[0039] (2) Prepare a mixture by mixing 0.8 mol / L sodium hydroxide solution and anhydrous ethanol in a volume ratio of 8:1; add the egg membrane powder obtained in step (1) to the mixture, with a ratio of egg membrane powder to mixture of 1 g: 12 mL, and hydrolyze at 55 °C for 1.5 h.
[0040] (3) Adjust the pH of the system after hydrolysis in step (2) to 10 using 0.1M NaOH solution, add alkaline protease and hydrolyze at 60℃ for 4 hours. The amount of alkaline protease used is 3×10 5 U / mL, after enzyme inactivation, centrifuge, and ultrafilter the supernatant using an ultrafiltration membrane with a molecular weight cutoff of 10kDa. Collect the retentate, freeze-dry and sterilize to obtain the final product.
[0041] This embodiment also provides a method for preparing a composite material containing a local anesthetic drug, comprising the following steps:
[0042] According to the specified ratio, mix bupivacaine hydrochloride, photothermal conversion agent, δ-juniperene, penetration enhancer, and glycerin evenly to obtain the final product.
[0043] Example 2
[0044] A composite material containing a local anesthetic drug comprises the following raw materials in parts by weight: 10 parts bupivacaine hydrochloride, 4 parts photothermal conversion agent, 0.5 parts δ-juniperene, 1 part penetration enhancer, and 2 parts glycerin.
[0045] The penetration enhancer is composed of egg membrane protein peptides and polylysine in a mass ratio of 1:1.
[0046] The preparation process of the photothermal conversion agent is as follows:
[0047] 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin and 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) were added to dimethyl sulfoxide at a molar ratio of 1:6. The amount of 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) and dimethyl sulfoxide was 1 mmol: 5 mL. The reaction was carried out at 175 °C for 45 h. After the reaction was completed, the reaction solution was cooled to room temperature, filtered, and washed with methanol, DMF, and TFH until the filtrate was colorless. After drying, the photothermal conversion agent was obtained.
[0048] The preparation process of egg membrane protein peptides is as follows:
[0049] (1) Take raw eggshells, clean them, add them to a 1 mol / L phosphoric acid solution, the mass of the phosphoric acid solution is 4 times that of the raw eggshells, soak them at 4℃ for 3 days, take out the egg membrane, wash the egg membrane, dry it, crush it and pass it through a 100-mesh sieve to obtain egg membrane powder.
[0050] (2) Prepare a mixture by mixing 0.5 mol / L sodium hydroxide solution and anhydrous ethanol in a volume ratio of 6:1; add the egg membrane powder obtained in step (1) to the mixture, with a ratio of egg membrane powder to mixture of 1 g: 10 mL, and hydrolyze at 50 °C for 2 h.
[0051] (3) Adjust the pH of the system after hydrolysis in step (2) to 9 using 0.1M NaOH solution, add alkaline protease and hydrolyze at 55℃ for 5h. The amount of alkaline protease used is 2×10 5 U / mL, after enzyme inactivation, centrifuge, and ultrafilter the supernatant using an ultrafiltration membrane with a molecular weight cutoff of 10kDa. Collect the retentate, freeze-dry and sterilize to obtain the final product.
[0052] This embodiment also provides a method for preparing a composite material containing a local anesthetic drug, comprising the following steps:
[0053] According to the specified ratio, mix bupivacaine hydrochloride, photothermal conversion agent, δ-juniperene, penetration enhancer, and glycerin evenly to obtain the final product.
[0054] Example 3
[0055] A composite material containing a local anesthetic drug comprises the following raw materials in parts by weight: 15 parts bupivacaine hydrochloride, 8 parts photothermal conversion agent, 1 part δ-juniperene, 3 parts penetration enhancer, and 5 parts glycerin.
[0056] The penetration enhancer is composed of egg membrane protein peptides and polylysine in a mass ratio of 1:3.
[0057] The preparation process of the photothermal conversion agent is as follows:
[0058] 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin and 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) were added to dimethyl sulfoxide at a molar ratio of 1:7. The amount of 3,3'-((1E,1'E)-(ethane-1,2-diylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) and dimethyl sulfoxide was 1 mmol: 6 mL. The reaction was carried out at 185 °C for 35 h. After the reaction was completed, the reaction solution was cooled to room temperature, filtered, and washed with methanol, DMF, and TFH until the filtrate was colorless. After drying, the photothermal conversion agent was obtained.
[0059] The preparation process of egg membrane protein peptides is as follows:
[0060] (1) Take raw eggshells, clean them, add them to a 1 mol / L phosphoric acid solution, the mass of the phosphoric acid solution is 6 times that of the raw eggshells, soak them at 4℃ for 3 days, then take out the egg membrane, wash the egg membrane, dry it, crush it and pass it through a 100-mesh sieve to obtain egg membrane powder.
[0061] (2) Prepare a mixture by mixing 1 mol / L sodium hydroxide solution and anhydrous ethanol in a volume ratio of 9:1; add the egg membrane powder obtained in step (1) to the mixture, with a ratio of egg membrane powder to mixture of 1 g: 15 mL, and hydrolyze at 50 °C for 2 h.
[0062] (3) Adjust the pH of the system after hydrolysis in step (2) to 11 using 0.1M NaOH solution, add alkaline protease and hydrolyze at 65℃ for 3 hours. The amount of alkaline protease used is 4×10 5 U / mL, after enzyme inactivation, centrifuge, and ultrafilter the supernatant using an ultrafiltration membrane with a molecular weight cutoff of 10kDa. Collect the retentate, freeze-dry and sterilize to obtain the final product.
[0063] This embodiment also provides a method for preparing a composite material containing a local anesthetic drug, comprising the following steps:
[0064] According to the specified ratio, mix bupivacaine hydrochloride, photothermal conversion agent, δ-juniperene, penetration enhancer, and glycerin evenly to obtain the final product.
[0065] Comparative Example 1
[0066] Comparative Example 1 is basically the same as Example 1, except that δ-juniperene is omitted.
[0067] Comparative Example 2
[0068] Comparative Example 2 is basically the same as Example 1, except that egg membrane protein peptides are replaced with polylysine.
[0069] Experimental Example 1
[0070] The infrared spectrum of the photothermal conversion agent obtained in Example 1 of this invention was tested, and the test results are shown in [Figure number missing]. Figure 1 .
[0071] Depend on Figure 1 It can be seen that the photothermal conversion agent was successfully applied at 3415 cm⁻¹. -1 The characteristic peak of secondary amine appears at 2954 cm⁻¹. -1 The characteristic peak of methylene appears at 1653 cm⁻¹, and at 1653 cm⁻¹... -1 The presence of a characteristic peak of imine indicates that the photothermal conversion agent has been successfully prepared.
[0072] Experimental Example 2
[0073] Forty-two female Kunming mice weighing 25-35g were randomly divided into four groups: Example 1, Example 2, Example 3, Comparative Example 1, Comparative Example 2, Control Group, and No Light Exposure Group, with six mice in each group. The mice were housed separately, with a 12-hour light and 12-hour dark cycle maintained at a temperature of 23±2℃ and a relative humidity of 50±5%. This acclimatization period lasted one week before being used in subsequent experiments.
[0074] Tween was added to the composite materials obtained in Examples 1-3 and Comparative Examples 1-2, and finally physiological saline was added. The concentration of the composite material in the water was 0.02 wt%, and the concentration of Tween in the water was 0.5 wt%. The mixture was sonicated and homogenized to obtain the test drug. The obtained test drug (0.5 g) was evenly applied to the hairless area on the back of each group of mice, and then near-infrared light (NIR, 808 nm, 1.0 W / cm²) was used. 2 The drug administration site was irradiated for 2 minutes. The drug administration in the non-irradiated group was the same as in Example 1, but without near-infrared light irradiation. The control group was treated with an equal volume of physiological saline and then irradiated with near-infrared light. After 48 hours, the skin surface was observed for any abnormal changes such as erythema or edema.
[0075] Table 1
[0076]
[0077] As shown in Table 1, after treatment with the material obtained in this invention, there were no significant differences between the mice in each group and the control group. This indicates that the composite material prepared in this invention is non-irritating to the skin and has good biocompatibility.
[0078] Experimental Example 3
[0079] Thirty-six female Kunming mice weighing 25-35g were randomly divided into four groups: Example 1, Example 2, Example 3, Comparative Example 1, Comparative Example 2, and No Light Exposure, with six mice in each group. The mice were housed separately, with a 12-hour light and 12-hour dark cycle maintained at a temperature of 23±2℃ and a relative humidity of 50±5%. This acclimatization period lasted one week before being used in subsequent experiments.
[0080] The mouse is placed in the groove of the restraint device, allowing its tail to relax naturally. A light source is used to illuminate the skin of the mouse's tail. When the animal shakes its tail, the light sensor inside the device detects the movement and stops timing, recording the latency at this time, which is the mouse's baseline latency.
[0081] The composite materials obtained in Examples 1-3 and Comparative Examples 1-2 were added to Tween, and finally physiological saline was added. The concentration of the composite material in the water was 0.02 wt%, and the concentration of Tween in the water was 0.5 wt%. The mixture was sonicated and homogenized to obtain the test drug. 0.5 g of the test drug was evenly applied to the tail of each group of mice, with the test drug corresponding to Example 1 applied to the non-illuminated group. Subsequently, except for the non-illuminated group, the other groups were exposed to near-infrared light (NIR, 808 nm, 1.0 W / cm²). 2 Irradiate the drug delivery site for 2 minutes.
[0082] At 10 min, 30 min, 1 h, 1.5 h, 2 h, and 3 h after drug administration, the tail skin of mice was irradiated with a light source, and the tail-flick latency was recorded at different times. To prevent tail injury, the tail-flick latency was set to not exceed 10 seconds; if it exceeded 10 seconds, the heat source was automatically cut off. The maximum possible analgesic effect (%) at different time points was calculated as follows: Maximum possible analgesic effect = (tail-flick latency - baseline latency) / (10 s - baseline latency) × 100%. The results are shown in Table 2.
[0083] Table 2
[0084]
[0085] As shown in Table 2, the materials obtained in this application can rapidly exert analgesic effects within 10 minutes, with a rapid onset of action. They still have a high maximum possible analgesic effect at 3 hours, providing long-lasting analgesia and avoiding the pain caused to patients by frequent medication changes.
[0086] Comparative Example 1, omitting δ-juniperene, showed a significantly lower maximum probable effect in mice 3 hours after administration compared to Example 1, indicating a reduced duration of analgesia. This is because δ-juniperene in the formulation enhances the analgesic effect and effectively prolongs the analgesic time. Comparative Example 2, replacing egg membrane protein peptides with polylysine, reduced the maximum probable effect to 75.93% after 2 hours of administration. This demonstrates that the synergistic effect of egg membrane protein peptides and polylysine is superior to their individual effects; their synergistic action promotes skin absorption of the active ingredient, effectively exerting analgesic effects.
[0087] The maximum possible analgesic effect in the group without phototherapy was lower than that in Example 1, and the duration of anesthesia was the shortest. This indicates that the photothermal conversion agent of the present invention can only effectively exert its analgesic effect after near-infrared light irradiation, allowing the composite material of the present invention to be released on demand during photothermal therapy, alleviating discomfort during photothermal therapy, and also solving the problems of short duration of action and frequent use of local anesthetics.
[0088] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.
Claims
1. A composite material containing a local anesthetic drug, characterized in that, The raw materials include the following parts by weight: 10-15 parts bupivacaine hydrochloride, 4-8 parts photothermal conversion agent, 0.5-1 part δ-juniperene, 1-3 parts penetration enhancer, and 2-5 parts glycerin.
2. The composite material containing a local anesthetic drug according to claim 1, characterized in that, The penetration enhancer is composed of egg membrane protein peptides and polylysine in a mass ratio of 1:(1-3).
3. The composite material containing a local anesthetic drug according to claim 1, characterized in that, The preparation process of the photothermal conversion agent is as follows: 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin and 3,3'-((1E,1'E)-(ethane-1,2-dimethylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) are added to a solvent and heated to react, thereby obtaining the photothermal conversion agent.
4. The composite material containing a local anesthetic drug according to claim 3, characterized in that, The molar ratio of 5,10,15,20-tetrakis(4-(2,4-diaminotriazine)phenyl)porphyrin to 3,3'-((1E,1'E)-(ethane-1,2-dimethylbis(azoethylene))bis(methaneethylene))bis(4-hydroxybenzaldehyde)-Fe(II) is 1:(2-8); the solvent is dimethyl sulfoxide.
5. The composite material containing a local anesthetic drug according to claim 3, characterized in that, The reaction is carried out at a temperature of 175-185℃ for 35-45 hours.
6. The composite material containing a local anesthetic drug according to claim 2, characterized in that, The preparation process of the egg membrane protein peptide is as follows: (1) Take raw eggshells, soak them in an acidic solution, remove the egg membrane, wash the egg membrane, dry it, and crush it to obtain egg membrane powder; (2) Add the egg membrane powder obtained in step (1) to the mixture and hydrolyze it; (3) Adjust the pH value of the system after hydrolysis in step (2), add alkaline protease for enzymatic hydrolysis, centrifuge after enzyme inactivation, take the supernatant for ultrafiltration, collect the retentate, freeze dry and sterilize to obtain the final product.
7. The composite material containing a local anesthetic drug according to claim 6, characterized in that, The mass of the acidic solution in step (1) is 4-6 times that of the raw eggshell; the acidic solution is a phosphoric acid solution with a concentration of 0.8-1.2 mol / L; the soaking temperature is 0-4℃ and the soaking time is 2-3 days.
8. The composite material containing a local anesthetic drug according to claim 6, characterized in that, In step (2), the ratio of egg membrane powder to the mixture is 1g:(10-15)mL; the mixture is composed of sodium hydroxide solution and anhydrous ethanol in a volume ratio of (6-9):1, and the concentration of the sodium hydroxide solution is 0.5-1mol / L; the hydrolysis temperature is 50-55℃ and the time is 1-2h.
9. The composite material containing a local anesthetic drug according to claim 6, characterized in that, The pH of the system in step (3) is 9-11; the amount of alkaline protease used is (2-4)×10. 5 U / mL; the enzymatic hydrolysis temperature is 55-65℃, and the time is 3-5h.
10. The method for preparing the composite material containing a local anesthetic drug according to any one of claims 1-9, characterized in that, Includes the following steps: According to the specified ratio, mix bupivacaine hydrochloride, photothermal conversion agent, δ-juniperene, penetration enhancer, and glycerin evenly to obtain the final product.