Choline-based melittin complex ionic liquid preparation, preparation method and application thereof

Abstract

The present invention relates to a choline-based melittin composite ionic liquid preparation and its preparation method and application. The choline-based melittin composite ionic liquid preparation comprises a composite ionic liquid and melittin formed by a choline 4-hydroxythiobenzamide ionic liquid and a choline lipoic acid ionic liquid in a certain mass ratio. The composite ionic liquid formed by the choline 4-hydroxythiobenzamide ionic liquid and the choline lipoic acid ionic liquid is selected as a carrier, and melittin with poor stability and transdermal absorbability is dissolved therein, which not only ensures the original efficacy of melittin, but also improves its skin permeability and stability. In addition, the choline-based melittin composite ionic liquid preparation has multifunctionality, exerts cascade antioxidant and anti-inflammatory effects with melittin, and can effectively regulate the body's immune response, and has broad application prospects in autoimmune diseases, inflammatory skin diseases and allergic diseases.

Description

TECHNICAL FIELD

[0001] The present application relates to the application of choline-based complex ionic liquid preparation in the field of biological medicine. In particular, it relates to a choline-based melittin complex ionic liquid preparation, its preparation method and application, especially to a choline-based melittin complex ionic liquid preparation, its preparation method and application in drug delivery and disease treatment. BACKGROUND

[0002] Autoimmune diseases, inflammatory skin diseases and allergic diseases are common health problems, which bring many inconveniences to the patients' life. At present, the treatment methods for these diseases mainly include topical application of steroid hormones, oral administration of antihistamines and injection of biological agents. In addition, some patients also choose traditional Chinese medicine treatment or use health products for auxiliary conditioning. These treatment methods cannot regulate the complex pathological microenvironment and all have some limitations. Topical application of steroids or oral administration of antihistamines is the main treatment method, however, long-term use of these drugs may cause thinning of the skin, pigmentation, telangiectasia and local irritation and other adverse reactions. Oral drugs need regular monitoring of adverse reactions of the body, because some drugs can cause damage to the function of organs such as liver and kidney. In addition, some drugs are prone to drug dependence, and even if the regular dose is used, withdrawal symptoms may occur after drug withdrawal, or even exacerbate the original condition. When injected in vitro, intradermal injection is often used, however, frequent intradermal injection can damage the skin tissue, causing local bleeding, ecchymosis and infection and other problems.

[0003] Melittin is the main component and main bioactive substance of bee venom, accounting for about 40% to 50% of the dry weight of bee venom, which is a polypeptide composed of 26 amino acid residues. Melittin is strongly alkaline and easily soluble in water, and plays a major pharmacological role in bee venom. It is one of the strongest anti-inflammatory substances known to humans. It has a hormone-like effect without causing adverse reactions of hormones, and also has the effects of antibacterial, anti-radiation, antiviral and antitumor. Melittin has been proven to treat a variety of diseases, but as a peptide drug, it is easily degraded by proteases in the stomach when taken orally, and its molecular weight is too large to penetrate the stratum corneum of the skin, so it is mainly treated by injection.

[0004] Therefore, it is essential to develop a new drug delivery system. This system should be able to avoid the low efficiency and side effects of oral administration, while having the high efficiency of injection administration, and also have the convenience, safety and compliance of transdermal patches. In addition, this new system should have multifunctionality and play a synergistic effect with drugs, so as to more effectively alleviate the development of diseases. SUMMARY

[0005] In view of the deficiencies of the prior art, the present application aims to provide a preparation method and application of a choline-based melittin complex ionic liquid preparation, which can avoid the low efficiency and side effects of oral administration, has the high efficiency of injection administration, is convenient, safe and compliant as a transdermal patch, and has multifunctionality and cascade antioxidant and anti-inflammatory effects of melittin.

[0006] The present application aims to provide a preparation method and application of a choline-based melittin complex ionic liquid preparation, and in particular, a preparation method of a choline-based melittin complex ionic liquid preparation and its application in drug delivery and disease treatment, which overcomes the problems of poor skin absorption, poor stability and low bioavailability of melittin, has high transdermal absorption efficiency, and can remain stable within a wide temperature range. The preparation can effectively regulate the immune response of the body and has a wide application prospect in autoimmune diseases, inflammatory skin diseases and allergic diseases.

[0007] To achieve the object of the present application, the following technical solutions are adopted:

[0008] In a first aspect, the present application provides a choline-based melittin complex ionic liquid preparation, which comprises a complex ionic liquid formed by mixing choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid at a mass ratio, and melittin.

[0009] The choline-based melittin complex ionic liquid preparation of the present application selects a choline-based complex ionic liquid as a carrier to encapsulate melittin with poor stability and transdermal absorption, which can ensure the original efficacy of melittin and improve its skin permeability and stability, thereby significantly improving the bioavailability of melittin. Moreover, the choline-based complex ionic liquid and melittin have a cascade synergistic effect in antioxidant and anti-inflammatory aspects.

[0010] The choline-based complex ionic liquid of the present application has the structure of choline 4-hydroxythiobenzamide, which is: The structure of choline lipoic acid is:

[0011] In a second aspect, the present application provides a preparation method of the choline-based melittin complex ionic liquid preparation of the first aspect, which comprises the following steps:

[0012] Step A, preparing a melittin solution;

[0013] Step B, ionization reaction of choline with lipoic acid or 4-hydroxythiobenzamide to obtain choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid, and mixing choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid in different mass ratios to obtain a composite ionic liquid;

[0014] Step C, mixing the composite ionic liquid and the melittin solution to obtain a choline-based melittin composite ionic liquid preparation.

[0015] The preparation method of the choline-based melittin composite ionic liquid preparation is simple, can be mass-produced, and is green and pollution-free.

[0016] In the step B, lipoic acid and 4-hydroxythiobenzamide are used as anion precursors, and choline is used as a cation precursor to synthesize ionic liquid through ionization reaction.

[0017] In embodiments, the step B specifically comprises:

[0018] Step B1, ionization reaction of lipoic acid or 4-hydroxythiobenzamide and choline in a solvent;

[0019] Step B2, concentrating the system after reaction to obtain the choline lipoic acid ionic liquid and the choline 4-hydroxythiobenzamide ionic liquid.

[0020] Step B3, mixing the obtained choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid in a certain mass ratio to obtain a composite ionic liquid.

[0021] The lipoic acid or 4-hydroxythiobenzamide and choline are mixed in a solvent such as ethanol or water to cause ionization reaction of the lipoic acid or 4-hydroxythiobenzamide and choline, and then ionic liquid is obtained through concentration. The ionic liquid has multiple biological activities and functions, and significantly improves the permeability, stability and bioavailability of melittin.

[0022] Optionally, the solvent is one or two of ethanol, water and methanol.

[0023] Optionally, the concentration comprises the following steps: concentrating the reaction liquid by using a rotary evaporator, and removing the excess solvent by vacuum drying to obtain the choline lipoic acid ionic liquid and the choline 4-hydroxythiobenzamide ionic liquid. The drying temperature is 30-100℃, and the drying time is 24-72 hours, so as to completely remove the residual water or ethanol in the product.

[0024] In a third aspect, the application further provides a choline-based melittin composite ionic liquid preparation as described in the first aspect for use in drug delivery and disease treatment.

[0025] Melittin is a natural substance with multiple pharmacological effects, which can not only resist inflammation and bacteria, but also resist radiation damage. In addition, melittin has been proved to have anti-viral and anti-tumor effects, and has a certain therapeutic effect on some infectious diseases and malignant tumors. Therefore, in the medical field, the potential value of melittin has been valued, and it is hoped that its pharmacological effects can be fully played through further scientific research and clinical trials. The present application relates to a preparation method of a choline-based melittin complex ionic liquid preparation and its application in drug delivery and disease treatment. The choline-based melittin complex ionic liquid preparation overcomes the disadvantages of poor skin absorption, poor stability and low bioavailability of melittin, has high transdermal absorption efficiency, and remains stable in a wide temperature range. The preparation can effectively regulate the immune response of the body, and has a broad application prospect in autoimmune diseases, inflammatory skin diseases and allergic diseases.

[0026] Compared with the prior art, the present application has the following beneficial effects:

[0027] The choline-based melittin complex ionic liquid preparation of the present application selects choline-based complex ionic liquid as a carrier, and wraps melittin with poor stability and transdermal absorption in it, which can not only ensure the original efficacy of melittin, but also improve its skin permeability and stability, and significantly improve the bioavailability of melittin. Moreover, the choline-based complex ionic liquid and melittin have a synergistic effect in antioxidant and anti-inflammatory aspects. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is the Fourier infrared spectrum of choline 4-hydroxythiobenzamide ionic liquid in example 10;

[0029] Figure 2 is the Fourier infrared spectrum of choline thioctic acid ionic liquid in example 10;

[0030] Figure 3 is the nuclear magnetic resonance hydrogen spectrum of choline 4-hydroxythiobenzamide ionic liquid in example 10;

[0031] Figure 4 is the nuclear magnetic resonance hydrogen spectrum of choline thioctic acid ionic liquid in example 10;

[0032] Figure 5 is the DPPH free radical scavenging rate of choline-based complex ionic liquid in example 10;

[0033] Figure 6 is the transdermal fluorescence diagram of choline-based complex ionic liquid in example 10;

[0034] Figure 7is a transdermal fluorescence quantification chart of the choline-based complex ionic liquid of Example 10. DETAILED DESCRIPTION

[0035] The technical solutions of the present application are further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments are only used to help understand the present application and should not be regarded as specific limitations on the present application.

[0036] Example 1

[0037] The present example provides a choline-based melittin ionic liquid preparation, which is prepared as follows:

[0038] Melittin is added to water to obtain a melittin solution.

[0039] A round-bottom flask is added with 0.1 mol of choline, followed by 0.1 mol of thioctic acid or 4-hydroxythiobenzamide and 5 mL of water and ethanol. Heating to 30°C, ionic reaction for 4 hours.

[0040] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying box for 48 hours to obtain choline thioctic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid.

[0041] The choline thioctic acid ionic liquid or choline 4-hydroxythiobenzamide ionic liquid and the melittin solution are mixed to obtain a choline-based melittin ionic liquid preparation.

[0042] Example 2

[0043] The present example provides a choline-based melittin ionic liquid preparation, which is prepared as follows:

[0044] Melittin is added to water to obtain a melittin solution.

[0045] A round-bottom flask is added with 0.1 mol of choline, followed by 0.1 mol of thioctic acid or 4-hydroxythiobenzamide and 5 mL of water and ethanol. Heating to 30°C, ionic reaction for 6 hours.

[0046] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying box for 48 hours to obtain choline thioctic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid.

[0047] The choline thioctic acid ionic liquid or choline 4-hydroxythiobenzamide ionic liquid and the melittin solution are mixed to obtain a choline-based melittin ionic liquid preparation.

[0048] Example 3

[0049] The present example provides a choline-based melittin ionic liquid preparation, which is prepared according to the following method:

[0050] The melittin is added to water to obtain a melittin solution.

[0051] In a round-bottom flask, 0.1 mol of choline is added, followed by 0.1 mol of lipoic acid or 4-hydroxythiobenzamide and 5 mL of water and ethanol. Heating to 40°C, ionic reaction for 4 hours.

[0052] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying oven for 48 hours to obtain choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid.

[0053] The choline lipoic acid ionic liquid or choline 4-hydroxythiobenzamide ionic liquid and the melittin solution are mixed to obtain a choline-based melittin ionic liquid preparation.

[0054] Example 4

[0055] The present example provides a choline-based melittin ionic liquid preparation, which is prepared according to the following method:

[0056] The melittin is added to water to obtain a melittin solution.

[0057] In a round-bottom flask, 0.1 mol of choline is added, followed by 0.1 mol of lipoic acid or 4-hydroxythiobenzamide and 5 mL of water and ethanol. Heating to 50°C, ionic reaction for 12 hours.

[0058] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying oven for 48 hours to obtain choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid.

[0059] The choline lipoic acid ionic liquid or choline 4-hydroxythiobenzamide ionic liquid and the melittin solution are mixed to obtain a choline-based melittin ionic liquid preparation.

[0060] Example 5

[0061] The present example provides a choline-based melittin ionic liquid preparation, which is prepared according to the following method:

[0062] The melittin is added to water to obtain a melittin solution.

[0063] In a round-bottom flask, 0.1 mol of choline is added, followed by 0.1 mol of lipoic acid or 4-hydroxythiobenzamide and 5 mL of water and ethanol. Heating to 50°C, ionic reaction for 4 hours.

[0064] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying oven for 48 hours to obtain the choline lipoic acid ionic liquid and the choline 4-hydroxythiobenzamide ionic liquid.

[0065] The choline lipoic acid ionic liquid or the choline 4-hydroxythiobenzamide ionic liquid is mixed with the melittin solution to obtain a choline-based melittin ionic liquid preparation.

[0066] Example 6

[0067] The present example provides a choline-based melittin ionic liquid preparation, which is prepared as follows:

[0068] The melittin is added to water to obtain a melittin solution.

[0069] In a round-bottom flask, 0.2 mol of choline is added, followed by the addition of 0.1 mol of lipoic acid or 4-hydroxythiobenzamide and 5 mL of water and ethanol. Heating is performed to 50°C, and the ionization reaction is performed for 4 hours.

[0070] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying oven for 48 hours to obtain the choline lipoic acid ionic liquid and the choline 4-hydroxythiobenzamide ionic liquid.

[0071] The choline lipoic acid ionic liquid or the choline 4-hydroxythiobenzamide ionic liquid is mixed with the melittin solution to obtain a choline-based melittin ionic liquid preparation.

[0072] Example 7

[0073] The present example provides a choline-based melittin ionic liquid preparation, which is prepared as follows:

[0074] The melittin is added to water to obtain a melittin solution.

[0075] In a round-bottom flask, 0.2 mol of choline is added, followed by the addition of 0.1 mol of lipoic acid or 4-hydroxythiobenzamide and 5 mL of water and ethanol. Heating is performed to 50°C, and the ionization reaction is performed for 4 hours.

[0076] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying oven for 48 hours to obtain the choline lipoic acid ionic liquid and the choline 4-hydroxythiobenzamide ionic liquid.

[0077] The choline lipoic acid ionic liquid or the choline 4-hydroxythiobenzamide ionic liquid is mixed with the melittin solution to obtain a choline-based melittin ionic liquid preparation.

[0078] Example 8

[0079] The present example provides a choline-based melittin ionic liquid preparation, which is prepared as follows:

[0080] Melittin is added to water to obtain a melittin solution.

[0081] In a round bottom flask, 0.3 mol of choline is added, followed by 0.2 mol of lipoic acid or 4-hydroxythiobenzoamide and 5 mL of water and ethanol. Heating to 50°C, ionic reaction for 4 hours.

[0082] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying oven for 48 hours to obtain choline lipoic acid ionic liquid and choline 4-hydroxythiobenzoamide ionic liquid.

[0083] The choline lipoic acid ionic liquid or choline 4-hydroxythiobenzoamide ionic liquid and the melittin solution are mixed to obtain a choline-based melittin ionic liquid preparation.

[0084] Example 9

[0085] The present example provides a choline-based melittin ionic liquid preparation, which is prepared as follows:

[0086] Melittin is added to water to obtain a melittin solution.

[0087] In a round bottom flask, 0.2 mol of choline is added, followed by 0.3 mol of lipoic acid or 4-hydroxythiobenzoamide and 5 mL of water and ethanol. Heating to 50°C, ionic reaction for 4 hours.

[0088] After the reaction is completed, the reaction solution is concentrated using a rotary evaporator, and then dried in a vacuum drying oven for 48 hours to obtain choline lipoic acid ionic liquid and choline 4-hydroxythiobenzoamide ionic liquid.

[0089] The choline lipoic acid ionic liquid or choline 4-hydroxythiobenzoamide ionic liquid and the melittin solution are mixed to obtain a choline-based melittin ionic liquid preparation.

[0090] Example 10

[0091] Preferably, the present example selects choline 4-hydroxythiobenzoamide ionic liquid formed by choline and 4-hydroxythiobenzoamide in Example 3 and choline lipoic acid ionic liquid formed by choline and lipoic acid in Example 4 to prepare a composite ionic liquid.

[0092] The present example provides a choline-based melittin composite ionic liquid preparation, which is prepared as follows:

[0093] Melittin is added to water to obtain a melittin solution.

[0094] The choline-based composite ionic liquid preparation is prepared by mixing the choline 4-hydroxythiobenzamide ionic liquid and the choline lipoic acid ionic liquid in a mass ratio of 6:4.

[0095] The choline-based melittin composite ionic liquid preparation is prepared by mixing the choline-based composite ionic liquid and the melittin.

[0096] Figure 1 and Figure 2 The Fourier infrared spectrum of the choline 4-hydroxythiobenzamide ionic liquid and the choline lipoic acid ionic liquid in this example.

[0097] Figure 3 and Figure 4 The nuclear magnetic resonance hydrogen spectrum of the choline 4-hydroxythiobenzamide ionic liquid and the choline lipoic acid ionic liquid in this example. The nuclear magnetic data of the choline 4-hydroxythiobenzamide ionic liquid are as follows: 1 H NMR (600 MHz, DMSO-d6) δ 7.15-7.07 (m, 1H), 6.19-6.12 (m, 1H), 4.11 (s, 2H), 3.84-3.79 (m, 3H), 3.57-3.46 (m, 2H), 3.46-3.38 (m, 3H), 3.17 (s, 1H), 3.13 (s, 12H), 2.56-2.51 (m, 4H). The nuclear magnetic data of the choline lipoic acid ionic liquid are as follows: 1 H NMR (600 MHz, DMSO-d6) δ 4.03 (s, 3H), 3.83 (tq, J = 6.5, 3.8, 3.3 Hz, 9H), 3.55 (pd, J = 7.1, 6.6, 3.3 Hz, 3H), 3.52-3.46 (m, 3H), 3.46-3.39 (m, 8H), 3.15 (d, J = 11.2 Hz, 5H), 3.12 (s, 30H), 1.85 (dp, J = 26.6, 6.9, 6.0 Hz, 7H), 1.56-1.52 (m, 1H), 1.41 (qd, J = 12.2, 10.0, 4.5 Hz, 5H), 1.29 (dddd, J = 16.4, 8.6, 6.0, 2.3 Hz, 5H).

[0098] Figure 5 The antioxidant evaluation of the choline-based composite ionic liquid in this example is shown in the table below. The specific method is as follows: different concentrations of the composite ionic liquid are mixed with DPPH solution, and the absorbance at 517 nm is measured by using an enzyme marker after 30 minutes of reaction in the dark, and the clearance rate is calculated. The antioxidant results show that the prepared composite ionic liquid can effectively scavenge DPPH·, and exhibits excellent antioxidant performance.

[0099] Figure 6 and Figure 7The fluorescence pictures and fluorescence quantification results of the choline-based complex ionic liquid transdermal delivery of melittin and PBS delivery of melittin in this example. The in vitro transdermal fluorescence results show that the complex ionic liquid can significantly promote the transdermal delivery of melittin compared with the PBS group.

[0100] Example 11

[0101] Preferably, the complex ionic liquid formed by choline 4-hydroxythiobenzamide ionic liquid and choline thioctic acid ionic liquid formed by choline and thioctic acid in Example 4 is selected in this example.

[0102] This example provides a choline-based melittin complex ionic liquid preparation, and the preparation method is as follows:

[0103] Melittin is added to water to obtain a melittin solution.

[0104] Preferably, the choline thioctic acid ionic liquid and the choline 4-hydroxythiobenzamide ionic liquid are mixed in a mass ratio of 5:5 to obtain a choline-based complex ionic liquid preparation.

[0105] The choline-based complex ionic liquid and melittin are mixed to obtain a choline-based melittin complex ionic liquid preparation.

[0106] Example 12

[0107] Preferably, the complex ionic liquid formed by choline 4-hydroxythiobenzamide ionic liquid and choline thioctic acid ionic liquid formed by choline and thioctic acid in Example 4 is selected in this example.

[0108] This example provides a choline-based melittin complex ionic liquid preparation, and the preparation method is as follows:

[0109] Melittin is added to water to obtain a melittin solution.

[0110] Preferably, the choline thioctic acid ionic liquid and the choline 4-hydroxythiobenzamide ionic liquid are mixed in a mass ratio of 4:6 to obtain a choline-based complex ionic liquid preparation.

[0111] The choline-based complex ionic liquid and melittin are mixed to obtain a choline-based melittin complex ionic liquid preparation.

[0112] Example 13

[0113] Preferably, the complex ionic liquid formed by choline 4-hydroxythiobenzamide ionic liquid and choline thioctic acid ionic liquid formed by choline and thioctic acid in Example 4 is selected in this example.

[0114] This example provides a choline-based melittin composite ionic liquid preparation, the preparation method of which is as follows:

[0115] Melittin is added into water to obtain a melittin solution.

[0116] Preferably, choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid are mixed in a mass ratio of 2:8 to obtain a choline-based composite ionic liquid preparation.

[0117] The choline-based composite ionic liquid and melittin are mixed to obtain a choline-based melittin composite ionic liquid preparation.

[0118] The applicant declares that the present invention uses the above-mentioned embodiments to illustrate a choline-based melittin composite ionic liquid formulation, its preparation method, and its application, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent replacement of various raw materials in the product of the present invention, addition of auxiliary ingredients, selection of specific methods, etc., all fall within the scope of protection and disclosure of the present invention.

[0119] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

[0120] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A choline-based melittin composite ionic liquid preparation, characterized in that: The choline-based melittin composite ionic liquid preparation comprises a composite ionic liquid and melittin, and the composite ionic liquid is formed by mixing a choline lipoic acid ionic liquid and a choline 4-hydroxythiobenzamide ionic liquid.

2. The choline-melittin composite ionic liquid preparation according to claim 1 is characterized in that the choline lipoic acid ionic liquid and the choline 4-hydroxythiobenzamide ionic liquid are mixed in different mass ratios.

3. The choline-based melittin composite ionic liquid preparation according to claim 1, wherein The preparation method comprises the following steps: Step A, preparing a melittin solution; Step B: ionizing choline with lipoic acid or 4-hydroxythiobenzamide to obtain choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid, and mixing the choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid in different mass ratios to obtain a composite ionic liquid. Step C: mixing the composite ionic liquid and the melittin solution to obtain a choline-based melittin composite ionic liquid preparation.

4. The method for preparing the choline-based melittin composite ionic liquid preparation according to claim 3, wherein: The preparation step of the melittin solution comprises: adding melittin into water to obtain the melittin solution.

5. The method for preparing the choline-based melittin composite ionic liquid preparation according to claim 3, wherein: The step B specifically includes: Step B1, adding choline and lipoic acid or 4-hydroxythiobenzamide to a solvent to carry out an ionization reaction; Step B2, concentrating the system after the reaction to obtain choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid; Step B3: mixing choline lipoic acid ionic liquid and choline 4-hydroxythiobenzamide ionic liquid in different mass ratios to obtain the choline-based composite ionic liquid.

6. The method for preparing the choline-based melittin composite ionic liquid preparation according to claim 3, wherein: The composite ionic liquid and the melittin solution are mixed to obtain a choline-based melittin composite ionic liquid.

7. The method for preparing the choline-based melittin composite ionic liquid preparation according to claim 5, wherein: The solvent is one or two of ethanol, water and methanol.

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