Preparation method of fritillary alkaloid-based analgesic hydrogel dressing

Abstract

The application discloses a preparation method of a pain-relieving hydrogel dressing based on fritillaria alkaloids, and belongs to the technical field of preparation of biomedical dressings, and comprises the following steps: dispersing fritillaria alkaloids in a hydrogel base material, and performing physical crosslinking or chemical crosslinking to obtain a pain-relieving hydrogel dressing based on fritillaria alkaloids. The core of the application is that fritillaria alkaloids with natural pain-relieving activity are combined with traditional polymer hydrogels, the sustained release characteristics of the hydrogels are utilized, the sustained release of the fritillaria alkaloids at a wound surface is realized, and the pain experience of a patient in a wound healing process is effectively reduced. Meanwhile, the hydrogel base itself has good moisturizing property, biocompatibility and healing-promoting characteristics, and can provide an ideal microenvironment for tissue repair. The application not only significantly reduces the pain feeling during wound repair, but also helps to speed up the wound healing process, improves the overall comfort and life quality of the patient, and has a wide clinical application prospect.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medical dressing preparation, and more specifically, the application relates to a preparation method of an analgesic hydrogel dressing based on fritillaria alkaloids. BACKGROUND

[0002] Wound repair materials have a wide range of applications in clinical treatment, especially in postoperative wound management, chronic ulcer and burn and scald care, and play a key role. The commonly used dressing materials at present include non-woven fabric, foam, alginate and hydrogel, etc. Among them, hydrogel can provide a moist, oxygen-permeable repair environment for wound tissue due to its good moisture retention, softness and biocompatibility, significantly promote cell proliferation and tissue regeneration, and has become an important research direction in the field of wound care.

[0003] However, the existing hydrogel dressing still has obvious deficiencies in relieving wound pain. Wound pain not only affects the quality of life of patients, but also may reduce their treatment compliance and prolong the rehabilitation period. Therefore, developing a new type of hydrogel material with analgesic function and repair ability has become a technical problem to be solved.

[0004] Traditional Chinese medicine resources have shown unique advantages in wound treatment. Fritillaria is a traditional medicinal material commonly used in traditional Chinese medicine for relieving cough, reducing sputum and anti-inflammatory, and its extract is rich in various bioactive alkaloid components such as phenacemide and fritidine, which have clear analgesic, anti-inflammatory and antibacterial activities. Although studies have shown its pharmacological potential, it is still immature to effectively load fritillaria alkaloids in a hydrogel system for sustained release and wound treatment.

[0005] Therefore, there is an urgent need for an innovative composite material combining traditional Chinese medicine active ingredients and modern hydrogel technology to achieve the synergistic effect of analgesia and wound repair, so as to meet the urgent needs of clinical safe, efficient and comfortable dressing materials. SUMMARY

[0006] An object of the present application is to solve at least the above problems and / or disadvantages and to provide at least the advantages described later.

[0007] In order to achieve these objects and other advantages according to the present application, a preparation method of an analgesic hydrogel dressing based on fritillaria alkaloids is provided, which specifically comprises the following steps:

[0008] Step one, using fritillaria alkaloids to prepare a fritillaria alkaloid solution with a concentration of 0.001wt%-0.1wt%;

[0009] Step two, the fritillaria alkaloids solution is mixed with the hydrogel matrix material precursor solution to obtain a composite solution; 5-15% of the mass of the hydrogel matrix material of modified polyacrylic acid is added to the composite solution; wherein the preparation method of the modified polyacrylic acid comprises:

[0010] S21, the hydroxylated nano-alumina is modified by using 3-(2,3-epoxypropoxy) propyl trimethoxysilane to obtain modified nano-alumina powder, and the specific method comprises: nano-alumina powder with a particle size of 20-60 nm is added to a 2-5wt% H2O2 solution, stirred at 1200-2000 rpm for 12-24 h, and then left to stand for 8-12 h; 3-(2,3-epoxypropoxy) propyl trimethoxysilane is added to the system, stirred at a speed of 200-600 rpm, and heated to 80-100°C for 6-24 h; after cooling and standing, centrifugal solid-liquid separation is performed, the solid powder is washed multiple times, and vacuum drying is performed at 50-80°C to obtain hydroxylated nano-alumina;

[0011] S22, the hydroxylated nano-alumina is dispersed in a 10-20wt% polyacrylic acid solution, polyethylene glycol-200 is used as a dispersant, the ultrasonic dispersion frequency is 40-80 kHz, the dispersion time is 1-2 h, and after standing for 12-24 h, the modified polyacrylic acid is obtained by evaporating water at 80-100°C;

[0012] Step three, a crosslinking agent is added to the composite solution to perform chemical crosslinking or physical crosslinking to form a three-dimensional network hydrogel structure, thereby obtaining a fritillaria alkaloid-based analgesic hydrogel dressing.

[0013] Preferably, in step one, the fritillaria alkaloids include one or more of isosteroid alkaloids, steroidal alkaloids, fritillarine, sotofenine, and luteimine; wherein the isosteroid alkaloids include fritillarine, fritillarine, fritillarine, sibimarine, isosotofenine, chuanbeine, and chuanbeitone.

[0014] Preferably, in step two, the concentration of the hydrogel matrix material in the hydrogel matrix material precursor solution is 0.5wt-50wt%.

[0015] Preferably, in step two, the hydrogel matrix material in the hydrogel matrix material precursor solution is one or more of chitosan, gelatin, chitin, cellulose, dextran, sodium alginate, polyacrylic acid, polyacrylamide, or hyaluronic acid.

[0016] Preferably, in step two, the fritillaria alkaloids in the hydrogel matrix material precursor solution are in the form of a solution, alkaloid powder, or alkaloid dispersion;

[0017] The added amount of the fritillaria alkaloid in the hydrogel matrix material precursor solution is 0.01% to 5% of the mass of the hydrogel matrix material.

[0018] Preferably, in the S21, the ratio of the amount of nano-aluminum oxide powder to the amount of H2O2 solution is 1 to 5:10 to 20 mL:1 to 10 mL.

[0019] Preferably, in the S22, the ratio of the amount of polyacrylic acid solution, hydroxylated nano-aluminum oxide, and polyethylene glycol-200 is 100 to 250 mL:1 to 5 g:0.1 to 1 g.

[0020] Preferably, in the step three, the cross-linking agent is added in the form of a cross-linking agent solution, the concentration of the cross-linking agent solution is 0 to 10 wt%, the volume of the cross-linking agent solution is 0 to 10% of the volume of the fritillaria alkaloid solution, and after the cross-linking agent is added, the cross-linking reaction includes one of freezing-thawing cycles and ultraviolet irradiation.

[0021] Preferably, in the step three, the method of physical cross-linking includes inducing crystallization or enhancing hydrogen bond interaction; the method of chemical cross-linking includes adding a cross-linking agent, and the cross-linking agent includes one or more of glutaraldehyde, genipin, and epichlorohydrin.

[0022] Preferably, the water content of the analgesic hydrogel dressing is 50% to 99.5%.

[0023] The present application at least includes the following beneficial effects:

[0024] (1) The analgesic hydrogel dressing based on fritillaria alkaloids provided by the present application not only has excellent wound repair performance, but also enhances the activity of inhibitory neurotransmitters (such as gamma-aminobutyric acid, GABA) through the sustained release of alkaloids, reduces the excitability of the central nervous system; at the same time, it blocks the nuclear factor kappa B (NF-κB) signaling pathway, effectively relieves inflammatory (such as arthritis) and neuropathic pain (such as cancer pain), thereby significantly reducing the pain of patients while promoting wound healing.

[0025] (2) The fritillaria alkaloids used have good biocompatibility with the hydrogel matrix, have no adverse effects on human metabolism during use, are highly safe, and are suitable for long-term or sensitive population use.

[0026] (3) The hydrogel matrix material used in the present application is a high-molecular network structure with sustained release performance, and the fritillaria alkaloids can be stably embedded in the structure and released continuously, thereby producing analgesic and healing effects on the wound site.

[0027] (4) The prepared analgesic hydrogel dressing based on fritillary alkaloids has analgesic and healing effects on the wound site, and has excellent mechanical properties. By adding hydroxylated nano aluminum oxide powder to polyacrylic acid, the excellent compatibility of the hydroxylated and coupled modified nano aluminum oxide powder with polyacrylic acid is improved, and polyethylene glycol-200 is used as a dispersant to improve the dispersion performance of the hydroxylated nano aluminum oxide powder in the polyacrylic acid solution. Among them, the nano aluminum oxide is treated by H2O2 to increase the hydroxyl density on the surface of the nano aluminum oxide powder, and a large number of active sites are provided for the subsequent reaction with 3-(2,3-epoxypropoxy) propyl trimethoxysilane; and the two end groups of 3-(2,3-epoxypropoxy) propyl trimethoxysilane (KH-560) are methoxy (-OCH3) and epoxy group, respectively. The methoxy group of KH-560 is hydrolyzed in an aqueous environment to generate highly reactive silanol (-SiOH). These silanols and the -OH on the surface of the hydroxylated nano aluminum oxide undergo dehydration condensation reaction to form a firm Al-O-Si covalent bond, which makes the KH-560 firmly anchored on the surface of the aluminum oxide particles, so that the nano aluminum oxide powder with inorganic properties has an organic compatible surface with a long chain and an epoxy group, thereby improving the compatibility of the hydroxylated nano aluminum oxide and the polyacrylic acid, and laying a foundation for improving the mechanical properties of the analgesic hydrogel dressing based on fritillary alkaloids; subsequently, the hydroxylated aluminum oxide powder is covalently crosslinked with the polyacrylic acid solution to form a three-dimensional crosslinked network, thereby improving the modulus, strength and toughness of the polyacrylic acid. Adding the modified polyacrylic acid to the mixed solution can significantly improve the tensile strength and yield strength of the analgesic hydrogel dressing based on fritillary alkaloids.

[0028] Other advantages, objects, and features of the present application will be apparent from the following specification, and will be understood by persons skilled in the art. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 The photo of the analgesic hydrogel dressing based on fritillary alkaloids prepared for Example 1;

[0030] Figure 2 Evaluation of cell compatibility of the analgesic hydrogel dressing based on fritillary alkaloids prepared for Example 1;

[0031] Figure 3 Evaluation of wound repair performance of the analgesic hydrogel dressing based on fritillary alkaloids prepared for Example 1;

[0032] Figure 4 The photo of the analgesic hydrogel dressing based on fritillary alkaloids prepared for Example 1; DETAILED DESCRIPTION

[0033] The application will be further described in detail below with reference to the accompanying drawings so that those skilled in the art can implement the application according to the description.

[0034] It should be understood that the terms such as "have", "contain" and "include" used herein do not exclude the presence or addition of one or more other elements or combinations thereof.

[0035] Example 1

[0036] A preparation method of a Fritillaria alkaloid-based analgesic hydrogel dressing, comprising the following steps:

[0037] Step one, 0.1 g of Fritillaria alkaloids (including 0.05 g of peimine and 0.05 g of peiminine) is dissolved in 100 mL of deionized water, and continuous stirring is carried out to make it uniformly dispersed. 10 g of gelatin powder is dissolved in 100 mL of deionized water, and heated to 60℃ to make it completely dissolved. The Fritillaria alkaloid solution and the gelatin solution are mixed, and continuous stirring is carried out to make them uniformly dispersed, to obtain a mixed solution.

[0038] Step two, 5 mL of glutaraldehyde solution with a concentration of 5wt% is added to the above mixed solution to crosslink the hydrogel, and after 10 min of crosslinking reaction, a Fritillaria alkaloid-based analgesic hydrogel dressing is obtained.

[0039] The photo of the Fritillaria alkaloid-based analgesic hydrogel dressing prepared in this example is shown in Figure 1 .

[0040] Figure 2 When a cell compatibility experiment is performed on the Fritillaria alkaloid-based analgesic hydrogel dressing prepared in Example 1, the adhesion photo of the cells on the surface of the Fritillaria alkaloid-based analgesic hydrogel dressing shows that the cells will only adhere to the surface of a material with good biocompatibility, and from Figure 2 it can be found that the cells have good adhesion properties on the surface of the Fritillaria alkaloid-based analgesic hydrogel dressing, indicating that the Fritillaria alkaloid-based analgesic hydrogel dressing has excellent cell compatibility and can be used as a hydrogel-based dressing.

[0041] Figure 3 The repair photo of the Fritillaria alkaloid-based analgesic hydrogel dressing prepared in this example after being implanted into the body of a mouse shows that the analgesic hydrogel is on the top and the blank control group is on the bottom. By comparison, it can be found that the wound of the group with the hydrogel dressing is almost completely closed, while the repair efficiency of the group without the hydrogel dressing is low.

[0042] Figure 4For the histological section of the repaired full-thickness wound, it can be found that a large amount of collagen is deposited after the repair by the analgesic hydrogel dressing based on the Fritillaria alkaloids, indicating that the maturity of the wound tissue of the mouse is high. No large amount of inflammatory cells is observed, indicating that the biocompatibility of our wound dressing is good.

[0043] Example 2

[0044] A preparation method of an analgesic hydrogel dressing based on Fritillaria alkaloids, comprising the following steps:

[0045] Step one, weigh 0.1 g of Fritillaria alkaloids (including 0.05 g of peimine and 0.05 g of peiminine) and dissolve it in 100 mL of deionized water, continuously stir to make it uniformly dispersed. Take 10 g of gelatin powder and dissolve it in 100 mL of deionized water, heat to 60℃ to make it completely dissolved. Mix the Fritillaria alkaloid solution with the gelatin solution, continuously stir to make it uniformly dispersed, and obtain a mixed solution.

[0046] Step two, transfer the above mixed solution to a 4℃ environment, and after 15 min of incubation, an analgesic hydrogel dressing based on Fritillaria alkaloids can be obtained.

[0047] Example 3

[0048] A preparation method of an analgesic hydrogel dressing based on Fritillaria alkaloids, comprising the following steps:

[0049] Step one, weigh 0.1 g of Fritillaria alkaloids (including 0.05 g of peimine and 0.05 g of peiminine) and dissolve it in 100 mL of deionized water, continuously stir to make it uniformly dispersed. Take 10 g of chitosan powder and dissolve it in 100 mL of deionized water, add 2 mL of glacial acetic acid to make it completely dissolved. Mix the Fritillaria alkaloid solution with the gelatin solution, continuously stir to make it uniformly dispersed, and obtain a mixed solution.

[0050] Step two, add 5 mL of glutaraldehyde solution with a concentration of 5wt% to the above mixed solution to crosslink the hydrogel, and after 10 min of crosslinking reaction, an analgesic hydrogel dressing based on Fritillaria alkaloids is obtained.

[0051] Example 4

[0052] A preparation method of an analgesic hydrogel dressing based on Fritillaria alkaloids, comprising the following steps:

[0053] Step one, weigh 0.1 g of Fritillaria alkaloids (including 0.05 g of peimine and 0.05 g of peiminine) and dissolve it in 100 mL of deionized water, continuously stir to make it uniformly dispersed. Take 10 g of chitosan powder and dissolve it in 100 mL of deionized water, add 2 mL of glacial acetic acid to make it completely dissolved. Mix the Fritillaria alkaloid solution with the gelatin solution, continuously stir to make it uniformly dispersed, and obtain a mixed solution.

[0054] Step two, 5 mL of 5 wt% genipin solution is added to the mixed solution to crosslink the hydrogel, and after 10 minutes of crosslinking reaction, the fangfeng alkaloid-based analgesic hydrogel dressing is obtained.

[0055] Example 5

[0056] A preparation method of a fangfeng alkaloid-based analgesic hydrogel dressing, comprising the following steps:

[0057] Step one, 0.1 g of fangfeng alkaloid (including 0.05 g of fangching A and 0.05 g of fangching B) is dissolved in 100 mL of deionized water, and continuous stirring is performed to uniformly disperse it. 10 g of gelatin powder is dissolved in 100 mL of deionized water, and heated to 60°C to completely dissolve it. The fangfeng alkaloid solution and the gelatin solution are mixed, and continuous stirring is performed to uniformly disperse them, to obtain a mixed solution.

[0058] Step two, 0.5 g of modified polyacrylic acid is added to the mixed solution, and 5 mL of 5 wt% glutaraldehyde solution is added to the mixed solution to crosslink the hydrogel, and after 10 minutes of crosslinking reaction, the fangfeng alkaloid-based analgesic hydrogel dressing is obtained.

[0059] The preparation method of the modified polyacrylic acid comprises:

[0060] S21, 25 g of nano-alumina powder with a particle size of 20-60 nm is added to 200 mL of 2 wt% H2O2 solution, stirred at 1200 rpm for 12 h, and left to stand for 12 h; 10 mL of 3-(2,3-epoxypropoxy) propyl trimethoxysilane is added to the system, stirred at a speed of 300 rpm and heated to 90°C for 12 h, and after cooling and standing, centrifugal solid-liquid separation is performed, the solid powder is washed with deionized water several times, and vacuum drying at 80°C is performed to obtain hydroxylated nano-alumina;

[0061] S22, 2 g of hydroxylated nano-alumina is dispersed in 250 mL of 20 wt% polyacrylic acid solution, 0.5 g of polyethylene glycol-200 is used as a dispersant, ultrasonic dispersion frequency is 80 kHz, dispersion time is 1 h, after standing for 24 h, 80°C evaporation is performed to remove water to obtain modified polyacrylic acid.

[0062] Example 6

[0063] A preparation method of a fangfeng alkaloid-based analgesic hydrogel dressing, comprising the following steps:

[0064] Step one, 0.1 g of fritillaria bioalkaloids (including 0.05 g of peimine and 0.05 g of peiminine) was dissolved in 100 mL of deionized water, and continuously stirred to uniformly disperse. 10 g of gelatin powder was dissolved in 100 mL of deionized water, heated to 60℃ to completely dissolve. The fritillaria bioalkaloid solution was mixed with the gelatin solution, and continuously stirred to uniformly disperse to obtain a mixed solution.

[0065] Step two, 0.5 g of modified polyacrylic acid was added to the mixed solution, and 5 mL of glutaraldehyde solution with a concentration of 5 wt% was added to the mixed solution to crosslink the hydrogel. After 10 min of crosslinking reaction, the analgesic hydrogel dressing based on fritillaria bioalkaloids was obtained.

[0066] The preparation method of the modified polyacrylic acid comprises:

[0067] S21, 25 g of nano-alumina powder with a particle size of 20-60 nm was added to 200 mL of 2 wt% H2O2 solution, stirred at 1200 rpm for 24 h, and then 10 mL of 3-(2,3-epoxypropoxy) propyl trimethoxysilane was added to the system. Stirring was carried out at a speed of 300 rpm and the temperature was raised to 90℃ for 12 h. After cooling and standing, centrifugal solid-liquid separation was carried out, and the solid powder was washed with deionized water several times, and then vacuum dried at 80℃ to obtain hydroxylated nano-alumina;

[0068] S22, 4 g of hydroxylated nano-alumina was dispersed in a 20 wt% polyacrylic acid solution, 0.5 g of polyethylene glycol-200 was used as a dispersant, ultrasonic dispersion was carried out at a frequency of 60 kHz for 1 h, and then the system was allowed to stand for 24 h. At 80℃, water was removed by evaporation to obtain modified polyacrylic acid.

[0069] Example 7

[0070] A preparation method of an analgesic hydrogel dressing based on fritillaria bioalkaloids comprises the following steps:

[0071] Step one, 0.1 g of fritillaria bioalkaloids (including 0.05 g of peimine and 0.05 g of peiminine) was dissolved in 100 mL of deionized water, and continuously stirred to uniformly disperse. 10 g of gelatin powder was dissolved in 100 mL of deionized water, heated to 60℃ to completely dissolve. The fritillaria bioalkaloid solution was mixed with the gelatin solution, and continuously stirred to uniformly disperse to obtain a mixed solution.

[0072] Step two, 0.5 g of modified polyacrylic acid was added to the mixed solution, and 5 mL of glutaraldehyde solution with a concentration of 5 wt% was added to the mixed solution to crosslink the hydrogel. After 10 min of crosslinking reaction, the analgesic hydrogel dressing based on fritillaria bioalkaloids was obtained.

[0073] The preparation method of the modified polyacrylic acid comprises:

[0074] S21, 25 g of nano-alumina powder with a particle size of 20-60 nm was added to 200 mL of H2O2 solution with a concentration of 3 wt%, stirred at 1200 rpm for 24 h, and left to stand for 12 h. 10 mL of 3-(2,3-epoxypropoxy) propyl trimethoxysilane was added to the system, stirred at a speed of 300 rpm, and heated to 90°C for 12 h. After cooling and standing, the solid-liquid was separated by centrifugation. The solid powder was washed several times with deionized water, and vacuum dried at 80°C to obtain hydroxylated nano-alumina.

[0075] S22, 5 g of hydroxylated nano-alumina was dispersed in a 20 wt% polyacrylic acid solution, 0.6 g of polyethylene glycol-200 was used as a dispersant, the ultrasonic dispersion frequency was 60 kHz, the dispersion time was 1 h, and after standing for 24 h, the water was removed by evaporation at 80°C to obtain modified polyacrylic acid.

[0076] Comparative Example 1

[0077] A preparation method of a pain-relieving hydrogel dressing based on fritillaria alkaloids, comprising the following steps:

[0078] Step one, 0.1 g of fritillaria alkaloids (including 0.05 g of fritillarin A and 0.05 g of fritillarin B) was dissolved in 100 mL of deionized water, and continuously stirred to uniformly disperse. 10 g of gelatin powder was dissolved in 100 mL of deionized water, and heated to 60°C to completely dissolve. The fritillaria alkaloid solution and the gelatin solution were mixed, and continuously stirred to uniformly disperse to obtain a mixed solution.

[0079] Step two, 0.5 g of modified polyacrylic acid was added to the mixed solution, and 5 mL of glutaraldehyde solution with a concentration of 5 wt% was added to the mixed solution to crosslink the hydrogel. After 10 min of crosslinking reaction, a pain-relieving hydrogel dressing based on fritillaria alkaloids was obtained.

[0080] The preparation method of the modified polyacrylic acid comprises:

[0081] 2 g of nano-alumina was dispersed in a 250 mL polyacrylic acid solution with a concentration of 20 wt%, 0.5 g of polyethylene glycol-200 was used as a dispersant, the ultrasonic dispersion frequency was 80 kHz, the dispersion time was 1 h, and after standing for 24 h, the water was removed by evaporation at 80°C to obtain modified polyacrylic acid.

[0082] Comparative Example 2

[0083] A preparation method of a pain-relieving hydrogel dressing based on fritillaria alkaloids, comprising the following steps:

[0084] Step one, 0.1 g of fritillaria bioalkaloids (including 0.05 g of peimine and 0.05 g of peiminine) was dissolved in 100 mL of deionized water, and continuously stirred to make it uniformly dispersed. 10 g of gelatin powder was dissolved in 100 mL of deionized water, and heated to 60°C to make it completely dissolved. The fritillaria bioalkaloid solution was mixed with the gelatin solution, and continuously stirred to make it uniformly dispersed to obtain a mixed solution.

[0085] Step two, 0.5 g of polyacrylic acid was added to the mixed solution, and 5 mL of glutaraldehyde solution with a concentration of 5 wt% was added to the mixed solution to crosslink the hydrogel, and the crosslinking reaction was carried out for 10 min to obtain the fritillaria bioalkaloid-based analgesic hydrogel dressing.

[0086] The tensile strength and yield strength of the fritillaria bioalkaloid-based analgesic hydrogel dressings obtained in Example 1, Example 5-Example 7 and Comparative Example 1-Comparative Example 2 were determined respectively, wherein the test method of the tensile strength and yield strength was referred to GB / T1040.1-2025, and the following table was obtained:

[0087] Table 1 Comparison of tensile strength and yield strength of analgesic hydrogel dressings of various samples

[0088]

[0089] As can be seen from the above table, the fritillaria bioalkaloid-based analgesic hydrogel dressings obtained by adding modified polyacrylic acid for crosslinking in Example 5-Example 7 have more excellent tensile strength and yield strength, which indicates that the modified polyacrylic acid obtained by crosslinking and modifying the polyacrylic acid with the hydroxylated nano-aluminum oxide powder can significantly improve the tensile strength and yield strength of the fritillaria bioalkaloid-based analgesic hydrogel dressing, and improve the mechanical properties of the fritillaria bioalkaloid-based analgesic hydrogel dressing.

[0090] The number of devices and the scale of processing described herein are used to simplify the description of the present application. Applications, modifications and variations of the present application that are obvious to those skilled in the art are obvious.

[0091] Although the embodiments of the present application have been disclosed as above, it is not limited to the applications and embodiments listed in the specification, and it can be fully applied to various fields suitable for the present application, and additional modifications can be easily realized by those skilled in the art, and therefore the present application is not limited to specific details and the figures shown and described herein, without departing from the general concept defined by the claims and the equivalent scope.

Claims

1. A method of preparing a fritillaria alkaloid-based analgesic hydrogel dressing, characterized by, Specifically comprising the following steps: Step one, using the fritillaria alkaloids to prepare a fritillaria alkaloids solution with a concentration of 0.001wt%-0.1wt%; Step two, mixing the fritillaria alkaloids solution with a hydrogel matrix material precursor solution to obtain a composite solution; To the composite solution, add 5%-15% of the mass of the hydrogel matrix material of modified polyacrylic acid; wherein the preparation method of the modified polyacrylic acid comprises: S21, add 20-60nm nano-alumina powder to a 2-5wt% H2O2 solution, stir and then stand; add 3-(2,3-epoxypropoxy) propyl trimethoxysilane to the system, stir and heat to react, centrifugal solid-liquid separation after cooling and standing, wash the solid powder several times, and vacuum dry at 50-80℃ to obtain modified nano-alumina powder; S22, ultrasonic dispersion of the modified nano-alumina powder in a 10-20wt% polyacrylic acid solution, use polyethylene glycol-200 as a dispersant, stand for 12-24h, and then evaporate the water to obtain modified polyacrylic acid; Step three, add a crosslinking agent to the composite solution with modified polyacrylic acid to form a three-dimensional network hydrogel structure by chemical crosslinking, or use a physical crosslinking method to form a three-dimensional network hydrogel structure, to obtain a fritillaria alkaloids-based analgesic hydrogel dressing.

2. The method of preparing a Fritillaria alkaloid-based analgesic hydrogel dressing according to claim 1, wherein the Fritillaria alkaloid-based analgesic hydrogel dressing is prepared by the following steps: In the step two, the concentration of the hydrogel matrix material in the hydrogel matrix material precursor solution is 0.5wt%-50wt%.

3. The method of preparing the Fritillaria alkaloid-based analgesic hydrogel dressing according to claim 1, characterized in that, In the step two, the hydrogel matrix material in the hydrogel matrix material precursor solution is one or more of chitosan, gelatin, chitin, cellulose, dextran, sodium alginate, polyacrylic acid, polyacrylamide, or hyaluronic acid.

4. The method of claim 1, wherein the preparation of the Fritillaria alkaloid-based analgesic hydrogel dressing is characterized by, In the step two, the fritillaria alkaloids in the hydrogel matrix material precursor solution is in the form of alkaloid powder or alkaloid dispersion; The addition amount of fritillaria alkaloids in the hydrogel matrix material precursor solution is 0.01%-5% of the mass of the hydrogel matrix material.

5. The method of preparing the Fritillaria alkaloid-based analgesic hydrogel dressing according to claim 1, characterized in that, In the S21, the dosage ratio of nano-alumina powder to H2O2 solution is 1-5:10-20mL:1-10mL.

6. The method for preparing the analgesic hydrogel dressing based on fritillaria alkaloids as described in claim 1, characterized in that, In the S22, the dosage ratio of polyacrylic acid solution, modified nano-alumina powder, and polyethylene glycol-200 is 100-250mL:1-5g:0.1-1g.

7. The method for preparing the analgesic hydrogel dressing based on fritillaria alkaloids as described in claim 1, characterized in that, In the step three, the crosslinking agent is in the form of a crosslinking agent solution, the concentration of the crosslinking agent solution is 0-10wt%, the volume of the crosslinking agent solution is 0-10% of the volume of the fritillaria alkaloids solution, and after adding the crosslinking agent, the crosslinking reaction includes one of freeze-thaw cycle and ultraviolet irradiation.

8. The method for preparing the analgesic hydrogel dressing based on fritillaria alkaloids as described in claim 1, characterized in that, In the step three, the physical crosslinking method includes inducing crystallization or enhancing hydrogen bond interaction; the chemical crosslinking method includes adding a crosslinking agent, and the crosslinking agent includes one or more of glutaraldehyde, genipin, and epichlorohydrin.

9. The method of preparing the Fritillaria alkaloid-based analgesic hydrogel dressing according to claim 1, characterized in that, The water content of the analgesic hydrogel dressing is 50%-99.5%.

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