Bioactive hyaluronic acid-based polymer as well as preparation method and application thereof

Abstract

The invention relates to a bioactive hyaluronic acid-based polymer as well as a preparation method and application thereof. Belongs to the technical field of biomedical materials, and the polymer is prepared by the following steps: dissolving oligomeric hyaluronic acid at room temperature, and adding a condensing agent to carry out amidation reaction with 3-aminophenylboronic acid to prepare an oligomeric hyaluronic acid-3-aminophenylboronic acid precursor polymer; adding natural active small molecules, connecting through dynamic boric acid bonds, and reacting at room temperature to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid-small molecule copolymer aqueous solution; and dialyzing the oligomeric hyaluronic acid-3-aminophenylboronic acid-small molecule copolymer aqueous solution, freeze-drying, and collecting the bioactive hyaluronic acid-based polymer. The material with good biocompatibility and anti-inflammatory and anti-oxidation functions is formed. The polymer can effectively inhibit epidermal thickening and inflammatory reaction caused by psoriasis, has the advantages of simple preparation, low cost and remarkable curative effect, and is suitable for development of psoriasis treatment drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical materials, and particularly relates to a bioactive hyaluronic acid-based polymer, a preparation method thereof, and an application thereof. Background Art

[0002] Psoriasis is a common chronic inflammatory skin disease, mainly characterized by epidermal flushing, epidermal hyperplasia, abnormal differentiation of keratinocytes, and immune system disorders. The pathogenesis of psoriasis is complex, involving abnormal activation of the immune system, overexpression of inflammatory factors, and enhanced oxidative stress response. At present, the treatment methods for psoriasis mainly include topical application of hormonal drugs, ultraviolet phototherapy, and systemic drug therapy. However, the existing treatment methods have problems such as large toxic and side effects, limited efficacy, and easy recurrence. Therefore, it is of great significance to develop therapeutic materials with good biocompatibility and anti-inflammatory and antioxidant functions.

[0003] In recent years, drug delivery systems based on natural polymer materials have received extensive attention due to their good biocompatibility, biodegradability, and low toxicity. However, most natural polymer drug delivery systems use raw materials with a molecular weight greater than 5000 Da, resulting in difficulty in penetrating the stratum corneum, the first barrier of the epidermis, and thus making it difficult to release effective substances for treating psoriasis lesions. Hyaluronic acid (HA), as a natural polysaccharide, has good biocompatibility and moisturizing properties, and has been widely used in skin repair and drug delivery systems. Its excellent water retention and moisturizing properties make it an effective component for effectively alleviating skin flushing and allergy in the cosmetics industry. However, as a natural polymer polysaccharide, hyaluronic acid has a wide molecular weight distribution. Oligo-hyaluronic acid (OHA) specifically refers to a type of hyaluronic acid with a molecular weight less than 10000 Da. In addition to good water retention and biocompatibility, it also has excellent transdermal permeability and can carry effective substances to the lesion site to play a role. 3-Aminophenylboronic acid (APBA), as a linker for small molecule active substances, is a compound containing a boronic acid group and can form dynamic borate ester bonds with molecules containing vicinal dihydroxy groups. Proanthocyanidins (PC) is a natural polyphenolic compound with significant antioxidant and anti-inflammatory activities, and can effectively scavenge free radicals and inhibit the expression of inflammatory factors. However, like most polyphenolic compounds, PC has very poor water solubility, which limits its absorption and utilization in the body. Moreover, if PC exists in the body in the form of monomers, it will be rapidly oxidized or enzymatically hydrolyzed, resulting in low bioavailability and poor stability. Summary of the Invention

[0004] To solve the problems of the existing technology, the present invention provides a bioactive hyaluronic acid-based polymer, a preparation method thereof, and an application thereof. The polymer has good biocompatibility, anti-inflammatory and antioxidant properties, and can effectively inhibit epidermal thickening and skin scales caused by psoriasis.

[0005] To achieve the above object, the present invention adopts the following technical solutions: The first object of the present invention is to provide a preparation method of a bioactive hyaluronic acid-based polymer. The method has a simple process and low cost, and the prepared polymer has good biocompatibility and anti-inflammatory and antioxidant properties. It includes: Performing an amide reaction on oligomeric hyaluronic acid and 3-aminophenylboronic acid at room temperature to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer; Connecting the oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer with procyanidins through dynamic borate bonds to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer; Purifying, freeze-drying and collecting the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer to obtain an anti-inflammatory and antioxidant polymer.

[0006] As a further improvement of the present invention, the molecular weight of the oligomeric hyaluronic acid is 100-5000 Da.

[0007] As a further improvement of the present invention, the natural polyphenol structure active small molecule contained is one or more of procyanidins, lycopene, quercetin, rutin, resveratrol, catechins and curcumin.

[0008] As a further improvement of the present invention, the molar ratio of 3-aminophenylboronic acid to oligomeric hyaluronic acid and condensing agent is (0.5-1):1:1.

[0009] As a further improvement of the present invention, the condensing agent used in the amidation reaction of 3-aminophenylboronic acid and oligomeric hyaluronic acid is 4-(4,6-dioxo-1,3,5-triazin-2-yl)-4-methyl-2-oxazolyl-5-oxo-2-chlorophenyl-trifluoroacetic anhydride (DMTMM).

[0010] As a further improvement of the present invention, the molar ratio of the oligomeric hyaluronic acid, condensing agent, and 3-aminophenylboronic acid is 1:1:(0.5-1); the molar ratio of the oligomeric hyaluronic acid-3-aminophenylboronic acid precursor polymer to the small molecule is 1:(0.5-1).

[0011] As a further improvement of the present invention, the temperature of the amide reaction is a one-pot reaction at room temperature (25-30 °C), without adjusting the pH step by step, and the reaction time is 20-30 hours.

[0012] As a further improvement of the present invention, the reaction temperature for the formation of the dynamic borate bond is 25-30 °C, and the reaction time is 2-6 hours.

[0013] As a further improvement of the present invention, the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer is purified by freeze-drying and collected, including: The aqueous polymer solution is dialyzed with a dialysis bag for 2-3 days, and then freeze-dried after dialysis and stored in a refrigerator.

[0014] The second object of the present invention is to provide a method for preparing a bioactive hyaluronic acid-based polymer, which is prepared by the above-mentioned method for preparing a bioactive hyaluronic acid-based polymer.

[0015] The third object of the present invention is to provide the application of the anti-inflammatory and antioxidant polymer in the treatment of psoriasis drugs. Specifically, it is applied to the epidermal thickening and increased scaling caused by psoriasis.

[0016] Compared with the prior art, the present invention has the following beneficial effects: In the present invention, an amide reaction is carried out between oligomeric hyaluronic acid and 3-aminophenylboronic acid, and then procyanidins are connected by the dynamic borate bond of boric acid to construct a polymer with good anti-inflammatory and antioxidant functions. The polymer not only has good biocompatibility and degradability, but also can effectively treat psoriasis by inhibiting inflammatory factors and scavenging free radicals. The preparation method of the present invention is simple, easy to operate, low in cost, and suitable for large-scale production. Experimental results prove that the anti-inflammatory and antioxidant polymer prepared by this method has good biocompatibility and good biological effects in vivo and in vitro, and can effectively treat psoriasis.

[0017] Furthermore, the oligomeric hyaluronic acid used in the present invention has good biocompatibility and moisturizing properties, and can effectively promote skin repair. 3-aminophenylboronic acid can form dynamic borate ester bonds with molecules containing vicinal dihydroxy groups, and has good reactivity and biocompatibility. Procyanidins have significant antioxidant and anti-inflammatory activities, and can effectively scavenge free radicals and inhibit the expression of inflammatory factors.

[0018] Furthermore, the polymer forms a material with good biocompatibility, anti-inflammatory and antioxidant functions by carrying out an amide reaction between OHA and 3-aminophenylboronic acid (APBA), and then connecting procyanidins (PC) by dynamic borate bonds. The low molecular weight (100-5000 Da) of OHA enhances the transdermal permeability of the material and solves the problem that traditional polymer drug delivery systems are difficult to penetrate the stratum corneum. PC is slowly released through dynamic borate bonds, improving its stability and bioavailability.

[0019] This polymer can effectively inhibit the epidermal thickening and inflammatory response caused by psoriasis, and has the advantages of simple preparation, low cost, and remarkable curative effect, and is suitable for the development of psoriasis treatment drugs. Description of the Drawings

[0020] Figure 1 is the structural formula of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer synthesized in the present invention; Figure 2 is the 1 H NMR spectrum of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer; Figure 3 is the FR-IR spectrum of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention; Figure 4 is the in vitro antioxidant result of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention; (a) is the appearance diagram of the prepared sample, and (b) is the in vitro antioxidant result; Figure 5 is the cytotoxicity assay of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention on human keratinocytes (HaCaT) and macrophages (RAW); (a) is the cytotoxicity assay of cells (HaCaT), and (b) is the cytotoxicity assay of macrophages (RAW); Figure 6 is the result of the in vivo treatment of psoriasis with the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention.

[0021] Figure 7 is the result of the epidermal thickening in the in vivo treatment of psoriasis with the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention. Detailed Embodiments

[0022] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application clearer, the present application will be further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0023] The embodiments are only used to explain the present application and are not used to limit the present application.

[0024] In the present application, the term "and / or" describes the association relationship of associated objects and indicates that three relationships may exist. For example, A and / or B may represent: A exists alone, A and B exist simultaneously, and B exists alone. Where A and B may be singular or plural. The character generally represents that the associated objects before and after are in an "or" relationship.

[0025] In this application, "at least one" means one or more, and "a plurality" means two or more. "At least one of the following" or similar expressions refer to any combination of these items, including any combination of single items or plural items. For example, "at least one of a, b, or c", or "at least one of a, b, and c" can both represent: a, b, c, a - b (i.e., a and b), a - c, b - c, or a - b - c, where a, b, and c can each be single or multiple.

[0026] It should be understood that in various embodiments of this application, the magnitude of the sequence numbers of the above - mentioned processes does not imply the order of execution. Some or all of the steps can be executed in parallel or successively. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation to the implementation process of the embodiments of this application.

[0027] The terms used in the embodiments of this application are only for the purpose of describing specific embodiments, and are not intended to limit this application. The singular forms "a", "the", and "said" used in the embodiments of this application and the appended claims are also intended to include the plural forms, unless the context clearly indicates otherwise.

[0028] The weight of the relevant components mentioned in the specification of the embodiments of this application not only can refer to the specific content of each component, but also can represent the proportional relationship of the weights between the components. Therefore, as long as the content of the relevant components in the specification of the embodiments of this application is scaled up or down proportionally, it is within the scope disclosed in the specification of the embodiments of this application. Specifically, the mass described in the specification of the embodiments of this application can be mass units well - known in the chemical industry such as mg, μg, g, kg, etc.

[0029] The first object of the present invention is to provide a method for preparing a bioactive hyaluronic acid - based polymer, including: dissolving oligomeric hyaluronic acid (OHA) at room temperature, adding a DMTMM condensing agent and 3 - aminophenylboronic acid to carry out an amidation reaction to prepare a copolymer precursor of oligomeric hyaluronic acid - 3 - aminophenylboronic acid, and then adding procyanidin (PC) at room temperature to connect with the boronic acid on the phenylboronic acid to synthesize an oligomeric hyaluronic acid - 3 - aminophenylboronic acid - procyanidin (HPB) copolymer.

[0030] In the present invention, an oligomeric hyaluronic acid is subjected to an amide reaction with 3-aminophenylboronic acid, and then procyanidins are linked through the dynamic boronic acid bonds of boric acid to construct a polymer with good anti-inflammatory and antioxidant functions. The design of this material utilizes the permeability and hydrophilicity of OHA to improve the solubility of the natural small molecule active substance PC, and the polymer realizes the sustained release of PC through dynamic borate ester bonds, thereby prolonging its action time and bioavailability. This polymer not only has good biocompatibility and degradability, but also can effectively treat psoriasis by inhibiting inflammatory factors and scavenging free radicals.

[0031] The present invention proposes a natural active polymer HPB for inhibiting epidermal thickening and epidermal scales caused by psoriasis. This method conducts an amidation reaction by using oligomeric hyaluronic acid, 3-aminophenylboronic acid, and a condensing agent 4-(4,6-dioxo-1,3,5-triazin-2-yl)-4-methyl-2-oxazolyl-5-oxo-2-chlorophenyl-trifluoroaceticanhydride (DMTMM).

[0032] The precursor copolymer intermediate prepared by this method is stable, has high condensation efficiency, is simple in method, and low in cost, and is suitable for large-scale industrial production. The oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer precursor reacts stably with procyanidins at room temperature and has a high degree of substitution, which can better exert the anti-inflammatory and antioxidant effects of the small molecule natural active substance PC. The natural polyphenol structure active small molecule material contained is procyanidins, and it can also be replaced by lycopene, quercetin, rutin, resveratrol, catechin, and curcumin.

[0033] The experimental results show that the bioactive hyaluronic acid-based polymer prepared by this method has good biocompatibility in vivo and in vitro, exhibits good antioxidant, anti-inflammatory effects, and inhibitory effects on epidermal thickening. Therefore, this polymer has good application prospects in the treatment of vulgar psoriasis and the inhibition of epidermal thickening.

[0034] In the examples, the hydrophilic base material is oligomeric hyaluronic acid (OHA), the condensing agent is 4-(4,6-dioxo-1,3,5-triazin-2-yl)-4-methyl-2-oxazolyl-5-oxo-2-chlorophenyl-trifluoroaceticanhydride (DMTMM), 3-aminophenylboronic acid, and the small molecule active substance with a natural polyphenol structure is procyanidins (PC).

[0035] As a further preference, the molar ratio of oligomeric hyaluronic acid, the condensing agent, and 3-aminophenylboronic acid is 1:1:(0.5-1), the reaction temperature is room temperature (25-30 °C), and the reaction time is 20-30 hours.

[0036] As a further preference, the molar ratio of the oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer to the procyanidin is 1:(0.5-1), the reaction temperature is room temperature (25-30 °C), and the reaction time is 2-6 hours.

[0037] In the examples, the HPB polymer also needs to be post-treated. The post-treatment method is as follows: after the reaction is completed, the HPB polymer solution is dialyzed with a dialysis bag for 2-3 days, and the dialyzed HPB polymer is freeze-dried and stored in the refrigerator.

[0038] The second object of the present invention is to provide a bioactive hyaluronic acid-based polymer, which is prepared by the above method. The synthesis method is simple and the cost is low, and it is applied in the preparation of drugs for the treatment of psoriasis.

[0039] The present invention will be further described in detail below with reference to the accompanying drawings: Example 1 A preparation method of a bioactive hyaluronic acid-based polymer of the present invention includes the following steps: 1) First, 1 mol of oligomeric hyaluronic acid (molecular weight 5000 Da) is dissolved in deionized water at room temperature (26 °C), 1 mol of condensing agent DMTMM and 0.5 mol of 3-aminophenylboronic acid are added, and the reaction is carried out at room temperature for 24 hours to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer.

[0040] 2) The oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer and procyanidin (0.5 mol) are reacted at room temperature for 2 hours, and an oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer is obtained through dynamic borate bond connection.

[0041] 3) The aqueous solution of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer is dialyzed with a dialysis bag for 2-3 days, and then freeze-dried and stored in the refrigerator after dialysis. An anti-inflammatory and antioxidant polymer based on oligomeric hyaluronic acid-phenylboronic acid-procyanidin is obtained.

[0042] Experiments were carried out on the anti-inflammatory and antioxidant polymer based on oligomeric hyaluronic acid-phenylboronic acid-procyanidin prepared by the preparation method of the present invention, and the experimental results are analyzed as follows: Figure 1 is the structural formula of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer synthesized by the present invention.

[0043] Figure 2 is of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer 1 1H NMR spectrum. The hyaluronic acid backbone has multiple characteristic peaks at 1.6-2.5 ppm and 3.5-4.3 ppm, and the dynamic borate ester bond has four characteristic peaks at 7.3-8.

[0044] Figure 3 The FR-IR spectrum of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention shows that the characteristic peak of the amide bond is at 3330 1579 and the characteristic peak of the borate ester bond is at 1371 .

[0045] Figure 4 The in vitro antioxidant results of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention are shown. (a) is the appearance of the prepared sample, and (b) is the in vitro antioxidant result. It can be seen that the polymer has good antioxidant effects.

[0046] Figure 5 The cytotoxicity assay of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention on human keratinocytes (HaCaT) and macrophages (RAW) is shown. (a) is the cytotoxicity assay of cells (HaCaT), and (b) is the cytotoxicity assay of macrophages (RAW). It can be seen that the polymer has good inhibitory effects on human keratinocytes and good biocompatibility with macrophages.

[0047] Figure 6 The results of in vivo treatment of psoriasis with the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention are shown. It can be seen from Figure 6 that the mice in the polymer group have less epidermal flushing and no obvious scale formation, indicating good treatment effects.

[0048] Figure 7 The results of epidermal thickening in the in vivo treatment of psoriasis with the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer prepared in the present invention are shown. Figure 7 It can be seen that the epidermal thickening in the copolymer group is well inhibited.

[0049] Example 2 A preparation method of a bioactive hyaluronic acid-based polymer according to the present invention includes the following steps: 1) First, 1 mol of oligomeric hyaluronic acid (with a molecular weight of 5000 Da) is dissolved in deionized water at room temperature (25°C), 1 mol of condensing agent DMTMM and 0.8 mol of 3-aminophenylboronic acid are added, and the reaction is carried out at room temperature for 30 hours to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer.

[0050] 2) The oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer is reacted with procyanidin (0.8 mol) at room temperature for 2 hours to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer through dynamic borate bond connection.

[0051] 3) Dialyze the aqueous solution of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer in a dialysis bag for 2 days, then freeze-dry the dialyzed solution and store it in the refrigerator. An anti-inflammatory and antioxidant polymer based on oligomeric hyaluronic acid-phenylboronic acid-procyanidin is obtained.

[0052] Example 3 A preparation method of a bioactive hyaluronic acid-based polymer according to the present invention comprises the following steps: 1) First, dissolve 1 mol of oligomeric hyaluronic acid (with a molecular weight of 5000 Da) in deionized water at room temperature (30 °C), add 1 mol of condensing agent DMTMM and 1 mol of 3-aminophenylboronic acid, and react at room temperature for 28 hours to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer.

[0053] 2) React the oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer with catechin (0.6 mol) at room temperature for 5 hours, and connect through dynamic borate bonds to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid-catechin polymer.

[0054] 3) Dialyze the aqueous solution of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer in a dialysis bag for 3 days, then freeze-dry the dialyzed solution and store it in the refrigerator. An anti-inflammatory and antioxidant polymer based on oligomeric hyaluronic acid-phenylboronic acid-catechin is obtained.

[0055] Example 4 A preparation method of a bioactive hyaluronic acid-based polymer according to the present invention comprises the following steps: 1) First, dissolve 1 mol of oligomeric hyaluronic acid (with a molecular weight of 5000 Da) in deionized water at room temperature (28 °C), add 1 mol of condensing agent DMTMM and 0.5 mol of 3-aminophenylboronic acid, and react at room temperature for 25 hours to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer.

[0056] 2) React the oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer with quercetin (0.9 mol) at room temperature for 3 hours, and connect through dynamic borate bonds to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid-quercetin polymer.

[0057] 3) Dialyze the aqueous solution of the oligomeric hyaluronic acid-3-aminophenylboronic acid-procyanidin polymer in a dialysis bag for 3 days, then freeze-dry the dialyzed solution and store it in the refrigerator. An anti-inflammatory and antioxidant polymer based on oligomeric hyaluronic acid-phenylboronic acid-quercetin is obtained.

[0058] Example 5 A preparation method of a bioactive hyaluronic acid-based polymer according to the present invention comprises the following steps: 1) First, dissolve 1 mol of oligomeric hyaluronic acid (with a molecular weight of 5000 Da) in deionized water at room temperature (27 °C). Add 1 mol of condensing agent DMTMM and 0.8 mol of 3-aminophenylboronic acid, and react at room temperature for 20 hours to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer.

[0059] 2) React the oligomeric hyaluronic acid-3-aminophenylboronic acid copolymer with lycopene (0.5 mol) at room temperature for 3 hours, and connect through dynamic borate bonds to obtain an oligomeric hyaluronic acid-3-aminophenylboronic acid-lycopene polymer.

[0060] 3) Dialyze the aqueous solution of the oligomeric hyaluronic acid-3-aminophenylboronic acid-proanthocyanidin polymer with a dialysis bag for 2 days, and then freeze-dry and store it in the refrigerator. An anti-inflammatory and antioxidant polymer based on oligomeric hyaluronic acid-phenylboronic acid-lycopene is obtained.

[0061] Examples 2-5 can also achieve the effects of Example 1 through experiments. They have a good inhibitory effect on human keratinocytes and good biocompatibility with macrophages.

[0062] It can be seen that the anti-inflammatory and antioxidant polymer based on oligomeric hyaluronic acid-3-aminophenylboronic acid-small molecule provided by the present invention has good biocompatibility, anti-inflammatory and antioxidant properties, and can effectively treat psoriasis. The preparation method of the present invention is simple, convenient to operate, and low in cost, and is suitable for large-scale production.

[0063] The above content is only to illustrate the technical idea of the present invention, and the protection scope of the present invention cannot be limited thereby. Any modification made on the basis of the technical solution according to the technical idea proposed by the present invention falls within the protection scope of the claims of the present invention.

Claims

1. A method for preparing a bioactive hyaluronic acid-based polymer, characterized in that: include: Dissolving oligomeric hyaluronic acid at room temperature, adding a condensing agent to react with 3-aminophenylboronic acid to undergo an amidation reaction, thereby preparing an oligomeric hyaluronic acid-3-aminophenylboronic acid precursor polymer; Then, natural active small molecules are added, connected through dynamic boric acid bonds, and reacted at room temperature to obtain an aqueous solution of oligomeric hyaluronic acid-3-aminophenylboronic acid-small molecule copolymer; The oligomeric hyaluronic acid-3-aminophenylboronic acid-small molecule copolymer aqueous solution was dialyzed and then freeze-dried to collect the bioactive hyaluronic acid-based polymer.

2. The method for preparing the bioactive hyaluronic acid-based polymer according to claim 1, characterized in that: The condensing agent is 4-(4,6-dioxo-1,3,5-triazine-2-yl)-4-methyl-2-oxazolyl-5-oxo-2-chlorophenyl-trifluoroacetic anhydride.

3. The method for preparing the bioactive hyaluronic acid-based polymer according to claim 1, characterized in that: The natural polyphenol structure active small molecules are one or more of proanthocyanidins, lycopene, quercetin, rutin, resveratrol, catechins and curcumin.

4. The method for preparing the bioactive hyaluronic acid-based polymer according to claim 1, characterized in that: The molar ratio of the oligomeric hyaluronic acid, the condensing agent and the 3-aminophenylboronic acid is 1:1:(0.5-1); the molar ratio of the oligomeric hyaluronic acid-3-aminophenylboronic acid precursor polymer to the small molecule is 1:(0.5-1).

5. The method for preparing the bioactive hyaluronic acid-based polymer according to claim 1, characterized in that: The amidation reaction is carried out at room temperature for 20 to 30 hours.

6. The method for preparing the bioactive hyaluronic acid-based polymer according to claim 1, characterized in that: The reaction of the oligomeric hyaluronic acid-3-aminophenylboronic acid precursor polymer and the small molecule is carried out at room temperature, and the reaction time is 2-6 hours.

7. The method for preparing the bioactive hyaluronic acid-based polymer according to claim 1, characterized in that: The method of dialyzing the aqueous solution of oligomeric hyaluronic acid-3-aminophenylboronic acid-small molecule copolymer and then freeze-drying to collect the bioactive hyaluronic acid-based polymer comprises: The oligomeric hyaluronic acid-3-aminophenylboronic acid-small molecule aqueous solution was dialyzed using a dialysis bag for 2-3 days, and the dialyzed solution was freeze-dried and stored in a refrigerator.

8. The method for preparing the bioactive hyaluronic acid-based polymer according to claim 1, characterized in that: The reaction temperature of the dynamic boronic acid bond connection is 25-30° C., and the reaction time is 2-6 hours.

9. A method for preparing a bioactive hyaluronic acid-based polymer, characterized in that: Prepared by the method according to any one of claims 1 to 8.

10. Use of the bioactive hyaluronic acid-based polymer obtained by the preparation method according to any one of claims 1 to 8, characterized in that: Application in the preparation of therapeutic drugs for psoriasis.

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