Preparation method and application of liposome hydrogel

Abstract

The invention discloses a preparation method of a lipidosome hydrogel. The preparation method comprises the following steps: preparing lipidosome; co-loading a target active ingredient into the liposome; the free target active component in the lipidosome is removed; performing morphological characterization on the liposome, wherein the morphological characterization comprises characterization of a scanning electron microscope, particle size determination, a transmission electron microscope, dynamic light scattering and stability; adding the lipidosome into a gel solution to form a lipidosome hydrogel preparation, and modifying the surface of the lipidosome. Through implementation of the technical scheme, on one hand, high-efficiency targeted drug delivery can be realized, high-concentration centralized drug effect exertion is facilitated, on the other hand, sebum secretion can be efficiently inhibited based on the synergistic effect of the components such as the oil-control peptide, and the process is simple.

Description

Technical Field

[0001] The embodiments of the present invention relate to the field of biomedicine technology, and in particular to a preparation method of a liposome hydrogel and its application. Background Art

[0002] Liposomes are ultramicrosphere carrier preparations formed by lipid bilayers. They are typical representatives of nano drug delivery systems and have been successfully applied to new drug delivery systems in clinical practice. Their structure is similar to that of biological membranes, and they can encapsulate hydrophilic and lipophilic components. They have good biocompatibility and can be used to deliver hydrophilic and lipophilic drugs. They have good application prospects and many advantages. Liposomes interact with stratum corneum lipids through their lipids, reducing their barrier function and increasing the amount of drugs that penetrate into the skin. They can also store drugs between the epidermis and dermis and form a drug reservoir, slowly releasing drugs and exerting a lasting effect, thus improving the therapeutic effect. Research on liposomes is also becoming more mature, with significant breakthroughs in the fields of anti-tumor, anti-fungal, analgesia, and gene therapy.

[0003] When liposomes in the prior art are combined with hydrogels, there is a problem of low encapsulation efficiency, such as usually resulting in a large amount of waste of free active ingredients, which has an adverse effect on the stability of the preparation. There is also a problem of uneven distribution, such as causing unstable liposome function and reducing its bioavailability in the target area.

[0004] The patent number is CN115068352B, and the patent name is: A flexible liposome hydrogel of oil-controlling polypeptide and its preparation method and application, including oil-controlling polypeptide, lecithin, cholesterol, surfactant, gel matrix and excipients, wherein the molar ratio of lecithin to cholesterol is 6:1; the molar ratio of lecithin to surfactant is 12:1; the molar ratio of lecithin to oil-controlling polypeptide is 300:1; the sum of oil-controlling polypeptide, lecithin, cholesterol and surfactant accounts for 6% of the total mass, the gel matrix accounts for 0.6% of the total mass, the excipients account for 5.1% of the total mass, and the rest is ultrapure water, and the lecithin is egg yolk lecithin and soybean lecithin and hydrogenated soybean lecithin, the surfactant is sodium deoxycholate, the gel matrix is ​​carbomer, the auxiliary materials include a humectant and a preservative, the humectant and the preservative account for 4%-7% and 0.1%-1% of the total mass of the hydrogel respectively, the humectant is one or a combination of hyaluronic acid, glycerol and ceramide; the preservative is one or a combination of methylparaben and ethylparaben, carbomer is selected as the gel matrix, a neutralizer needs to be added to the auxiliary materials, the neutralizer accounts for 0-0.3% of the total mass of the hydrogel, and the neutralizer is one or a combination of triethanolamine, diethanolamine, ethylenediamine and calcium chloride.

[0005] However, actual use and market research have shown that the overall preparation process in the prior art is complicated, and there are problems such as low liposome encapsulation rate and uneven distribution of liposomes, which have an adverse effect on the stability of the preparation. Summary of the invention

[0006] The embodiment of the present invention provides a preparation method of a liposome hydrogel and application thereof, which solves the problems in the above-mentioned background technology.

[0007] The present invention provides a method for preparing a liposome hydrogel, comprising the following steps:

[0008] preparing liposomes;

[0009] co-loading a target active ingredient into the liposome;

[0010] removing the free target active ingredient in the liposome;

[0011] The liposomes are characterized by morphology, including scanning electron microscopy, particle size determination, transmission electron microscopy, dynamic light scattering, and stability;

[0012] The liposome is added into a gel solution to form a liposome hydrogel preparation, and the surface of the liposome is modified.

[0013] Specifically, the target active ingredient is any one of the structures of oil-controlling peptides, oil-controlling ingredients, or anti-inflammatory ingredients.

[0014] Specifically, the method for preparing liposomes comprises:

[0015] 7 parts by weight of phospholipid, 2 parts by weight of cholesterol, 1 part by weight of lipid, and 1 part by weight of polyvinyl alcohol are selected to form a membrane material;

[0016] Add 10 mL to 20 mL of chloroform to the membrane material;

[0017] The membrane material is subjected to a first ultrasonic treatment for 5-10 minutes, the ultrasonic frequency is adjusted to 20-40 kHz, and the power is set to 20-30, so that the membrane material is fully dissolved in the chloroform to form a chloroform solution;

[0018] The chloroform solution is placed in a vacuum environment to evaporate the chloroform to form liposomes.

[0019] Specifically, the method of co-loading the target active ingredient into the liposome comprises:

[0020] The method of placing the chloroform solution in a vacuum environment to evaporate the chloroform to form liposomes comprises:

[0021] The chloroform solution is transferred to an evaporating bottle of a rotary evaporator, the rotation speed is set to 100-200 rpm, the rotation temperature is set to 40-50° C., and the evaporation of chloroform is accelerated by heating and rotation;

[0022] The chloroform solution is subjected to vacuum treatment to maintain the pressure in the evaporating flask below 10-20 kPa to accelerate the volatilization of chloroform;

[0023] During the rotary evaporation process, liposomes gradually form from the container wall in the evaporation flask;

[0024] After the chloroform is evaporated, uniform liposomes are obtained, and the liposomes appear as transparent or milky white films.

[0025] Specifically, the method of co-loading the target active ingredient into the liposome includes:

[0026] Dissolve sodium dihydrogen phosphate and disodium hydrogen phosphate in deionized water and adjust the pH value to 7.0-7.4 to form a buffer solution;

[0027] adding oil-controlling peptides or oil-controlling ingredients or anti-inflammatory ingredients to the buffer;

[0028] Hydrate the lipid membrane with a buffer containing the oil-control peptide or oil-control component or anti-inflammatory component;

[0029] The hydrated liposomes having the oil-controlling peptide or oil-controlling component or anti-inflammatory component are placed in a tube;

[0030] The hydrated liposomes are subjected to a second ultrasonic treatment, the ultrasonic treatment time is 5-10 minutes, the frequency is 20 kHz to 40 kHz, and the power is adjusted to 30%-40%;

[0031] Transferring the ultrasonically treated liposome suspension to a membrane filtration device with a small pore size of 100 nm to 500 nm;

[0032] The liposomes are squeezed through a membrane with a small pore size, and the oil-controlling peptide or oil-controlling component or anti-inflammatory component is effectively encapsulated in the liposomes to obtain uniformly distributed liposomes with the oil-controlling peptide or oil-controlling component or anti-inflammatory component.

[0033] Specifically, the method for removing the free target active ingredient in the liposome comprises:

[0034] Taking the prepared liposomes having the target active ingredient, adding them to the emulsion solution to form a liposome solution;

[0035] The liposome solution is added to the activated dialysis bag and allowed to sink for 7 to 12 hours to remove the unencapsulated target active ingredient.

[0036] Specifically, the liposomes are characterized by morphology, including scanning electron microscopy, particle size determination, transmission electron microscopy, dynamic light scattering, and stability. The characterization methods include:

[0037] Electron microscopy: drop the liposome solution onto a conductive sample support, and after drying, use a scanning electron microscope to observe the surface morphology of the sample;

[0038] Particle size determination: using a laser particle size analyzer to measure the average particle size and particle size distribution of the liposomes to evaluate the particle size and distribution uniformity of the liposomes;

[0039] Transmission electron microscopy, using dynamic light scattering technology to calculate the width of the liposome size distribution, the smaller the PDI value, the narrower the distribution and the better the particle uniformity;

[0040] Dynamic light scattering: the liposome solution is dropped on a carbon film, and a transmission electron microscope is used to observe the internal structure of the sample to observe the internal structure of the liposome, the thickness of the membrane, and the membrane stacking.

[0041] Specifically, the liposomes are characterized by morphology, including scanning electron microscopy, particle size, PDI, Zeta potential, transmission electron microscopy, in vitro release performance, storage stability, in vivo and in vitro uptake, and cytotoxicity. The method also includes:

[0042] The storage stability of the liposomes was tested, LRn represented the leakage rate at the nth month, C0 represented the oil-control peptide concentration at the initial time point (0 months), and Cn represented the oil-control peptide concentration at the nth month. The calculation formula for calculating the leakage rate of the free oil-control peptide removed from the liposomes was:

[0043]

[0044] Specifically, the method of adding the liposome into a gel solution to form a liposome hydrogel preparation and modifying the surface of the liposome includes:

[0045] Slowly adding the liposomes into the gel solution and stirring evenly to make the liposomes evenly dispersed in the gel matrix to form a liposome hydrogel preparation;

[0046] The PEG with active groups at the end of the liposome is coupled with the phospholipids on the surface of the liposome through chemical reaction.

[0047] Specifically, the liposome hydrogel prepared by the method is used as a sebum secretion inhibiting agent.

[0048] The technical solution of the embodiment of the present invention combines a drug that inhibits sebum (oil-controlling peptides or oil-controlling ingredients or anti-inflammatory ingredients) with targeted liposomes to construct targeted liposomes that encapsulate oil-controlling peptides or oil-controlling ingredients or anti-inflammatory ingredients. The ratio of cholesterol, phospholipids and lipids is precisely controlled, the lipid membrane is hydrated using a buffer solution containing the target active ingredient, ultrasonic treatment and small-pore membrane extrusion technology are used, dialysis is used to remove free target active ingredients, and the particle size and uniformity of the secondary liposomes are optimized. This can improve the encapsulation rate and distribution uniformity of the liposomes, the production process is simple and convenient, and the hydrocoagulant has high stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 This is a flow chart of a method for preparing a liposome hydrogel in the present invention;

[0050] Figure 2 It is the liposome characterization result;

[0051] Figure 3 This is a diagram to verify the effect of the prepared liposomes encapsulating the target active ingredient. DETAILED DESCRIPTION

[0052] The present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It is to be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention. It should also be noted that, for ease of description, only parts related to the present invention, rather than all structures, are shown in the accompanying drawings.

[0053] It should be mentioned before discussing the exemplary embodiments in more detail that some exemplary embodiments are described as processes or methods depicted as flow charts. Although the flow charts describe the steps as sequential processes, many of the steps therein can be implemented in parallel, concurrently or simultaneously. In addition, the order of the steps can be rearranged. The process can be terminated when its operation is completed, but can also have additional steps not included in the accompanying drawings. The process can correspond to a method, function, procedure, subroutine, subprogram, etc.

[0054] Embodiment 1

[0055] Please refer to Figure 1 , Figure 1 The present invention is a flow chart of a method for preparing a liposome hydrogel, comprising the following steps:

[0056] Preparation of liposome 01;

[0057] Co-loading the target active ingredient into the liposome 02;

[0058] Removing the free target active ingredient 03 in the liposome;

[0059] The liposomes are characterized by morphology, including scanning electron microscopy, particle size determination, transmission electron microscopy, dynamic light scattering and stability.

[0060] The liposomes are added into a gel solution to form a liposome hydrogel preparation, and the surface of the liposomes is modified 05.

[0061] Encapsulating the target active ingredient in liposomes can protect it from degradation by the external environment and improve its stability. At the same time, liposomes have good biocompatibility and biodegradability, which can enhance the absorption and utilization of active ingredients.

[0062] Liposomes have natural targeting properties and can deliver active ingredients to the lesion site more accurately, reducing the impact on healthy tissues and thus reducing side effects and toxicity.

[0063] Specifically, the target active ingredient is any one of the structures of oil-controlling peptides, oil-controlling ingredients, or anti-inflammatory ingredients.

[0064] Oil-control peptides can regulate sebum secretion, regulate the activity of sebaceous glands, reduce sebum secretion, prevent oil accumulation and pore clogging, are gentle and non-irritating, and are suitable for long-term use.

[0065] Oil-control ingredients can reduce shine and prevent acne: Salicylic acid, zinc salts and other oil-control ingredients can effectively reduce shine on the skin surface and keep the skin fresh. Oil-control ingredients can prevent acne and blackheads caused by excessive sebum secretion.

[0066] Anti-inflammatory ingredients can reduce inflammation and promote healing.

[0067] The method for preparing liposomes comprises:

[0068] 7 parts by weight of phospholipid, 2 parts by weight of cholesterol, 1 part by weight of lipid, and 1 part by weight of polyvinyl alcohol are selected to form a membrane material;

[0069] Add 10 mL to 20 mL of chloroform to the membrane material;

[0070] The membrane material is subjected to a first ultrasonic treatment for 5-10 minutes, the ultrasonic frequency is adjusted to 20-40 kHz, and the power is set to 20-30, so that the membrane material is fully dissolved in the chloroform to form a chloroform solution;

[0071] The chloroform solution is placed in a vacuum environment to evaporate the chloroform to form liposomes.

[0072] According to the preset ratio of 7; 2; 1, select appropriate phospholipids, cholesterol and other lipids (such as unsaturated fatty acids, fatty alcohols, etc.) to prepare liposome membrane materials. Common phospholipids include soybean lecithin, egg phosphatidylcholine or other plant-derived phospholipids, and users can choose according to actual conditions. Cholesterol is used to adjust the fluidity and stability of the lipid membrane.

[0073] Add chloroform (or other organic solvents such as toluene or methyl vinyl chloride) to the membrane. Chloroform is a commonly used solvent that can effectively dissolve phospholipids and cholesterol.

[0074] The dissolved membrane material is first sonicated using an ultrasonic device to improve the solubility and uniformity of the membrane material. Sonication helps break up large liposome membranes, ensures uniform distribution of the membrane material, and reduces aggregation.

[0075] The method of placing the chloroform solution in a vacuum environment to evaporate the chloroform to form liposomes comprises:

[0076] The chloroform solution is transferred to an evaporating bottle of a rotary evaporator, the rotation speed is set to 100-200 rpm, the rotation temperature is set to 40-50° C., and the evaporation of chloroform is accelerated by heating and rotation;

[0077] The chloroform solution is subjected to vacuum treatment to maintain the pressure in the evaporating flask below 10-20 kPa to accelerate the volatilization of chloroform;

[0078] During the rotary evaporation process, liposomes gradually form from the container wall in the evaporation flask;

[0079] After the chloroform is evaporated, uniform liposomes are obtained, and the liposomes appear as transparent or milky white films.

[0080] Specifically, the method of co-loading the target active ingredient into the liposome includes:

[0081] Dissolve sodium dihydrogen phosphate and disodium hydrogen phosphate in deionized water and adjust the pH value to 7.0-7.4 to form a buffer solution;

[0082] adding oil-controlling peptides or oil-controlling ingredients or anti-inflammatory ingredients to the buffer;

[0083] Hydrate the lipid membrane with a buffer containing the oil-control peptide or oil-control component or anti-inflammatory component;

[0084] The hydrated liposomes having the oil-controlling peptide or oil-controlling component or anti-inflammatory component are placed in a tube;

[0085] The hydrated liposomes are subjected to a second ultrasonic treatment, the ultrasonic treatment time is 5-10 minutes, the frequency is 20 kHz to 40 kHz, and the power is adjusted to 30%-40%;

[0086] Transferring the ultrasonically treated liposome suspension to a membrane filtration device with a small pore size of 100 nm to 500 nm;

[0087] The liposomes are squeezed through a membrane with a small pore size, and the oil-controlling peptide or oil-controlling component or anti-inflammatory component is effectively encapsulated in the liposomes to obtain uniformly distributed liposomes with the oil-controlling peptide or oil-controlling component or anti-inflammatory component.

[0088] Specifically, the method for removing the free target active ingredient in the liposome comprises:

[0089] Taking the prepared liposomes having the target active ingredient, adding them to the emulsion solution to form a liposome solution;

[0090] The liposome solution is added to the activated dialysis bag and allowed to sink for 7 to 12 hours to remove the unencapsulated target active ingredient.

[0091] It should be noted that, through a large number of experiments and data experiments, the above parameters are comprehensively controlled so that the prepared liposomes have good stability and encapsulation properties, the process is simple, and has beneficial effects.

[0092] Embodiment 2

[0093] This example is used to characterize the liposomes encapsulating the target active ingredient prepared in Example 1.

[0094] Specifically, the liposomes are characterized by morphology, including scanning electron microscopy, particle size determination, transmission electron microscopy, dynamic light scattering, and stability. The characterization methods include:

[0095] Electron microscope: drop the liposome solution onto a conductive sample support, and after drying, use a scanning electron microscope to observe the surface morphology of the sample; observe the surface morphology of the liposome to ensure that its structure is intact and evenly distributed.

[0096] Particle size determination: using a laser particle size analyzer to measure the average particle size and particle size distribution of the liposomes to evaluate the particle size and distribution uniformity of the liposomes;

[0097] Transmission electron microscopy, through the dynamic light scattering technology, calculates the width of the liposome size distribution. The smaller the PDI value, the narrower the distribution and the better the particle uniformity. The internal structure of the liposome is observed to confirm the encapsulation of the active ingredient.

[0098] Dynamic light scattering, drop the liposome solution on the carbon film, and use a transmission electron microscope to observe the internal structure of the sample to observe the internal structure of the liposome, the thickness of the membrane, and the membrane stacking. The particle size and polydispersity index (PDI) of the liposome are measured to evaluate its uniformity and distribution.

[0099] Specifically, the liposomes are characterized by morphology, including scanning electron microscopy, particle size, PDI, Zeta potential, transmission electron microscopy, in vitro release performance, storage stability, in vivo and in vitro uptake, and cytotoxicity. The method also includes:

[0100] The storage stability of the liposomes was tested, LRn represented the leakage rate at the nth month, C0 represented the oil-control peptide concentration at the initial time point (0 months), and Cn represented the oil-control peptide concentration at the nth month. The calculation formula for calculating the leakage rate of the free oil-control peptide removed from the liposomes was:

[0101]

[0102] It should be noted that the liposomes were characterized by morphology, the physicochemical properties of the liposomes under different storage conditions were evaluated, and the storage stability of the liposomes was evaluated based on the leakage rate.

[0103] The characterization results are as follows Figure 2 As shown, the average particle size of the liposome is 285 nm, which meets the liposome nanoparticle size required by the experiment, proving that the liposome is successfully prepared.

[0104] Specifically, the method of adding the liposome into a gel solution to form a liposome hydrogel preparation and modifying the surface of the liposome includes:

[0105] Slowly adding the liposomes into the gel solution and stirring evenly to make the liposomes evenly dispersed in the gel matrix to form a liposome hydrogel preparation;

[0106] The PEG with active groups at the end of the liposome is coupled with the phospholipids on the surface of the liposome through chemical reaction.

[0107] Functional molecules, such as polyethylene glycol, are modified on the surface of liposomes to improve their stability and biocompatibility.

[0108] Hydrogel preparations have good rheology and spreadability, making them easy to apply evenly on the skin or other surfaces. The liposomes in the hydrogel can achieve sustained release of active ingredients, further prolonging their duration of action. The hydrogel has good moisturizing effects, can relieve skin dryness and discomfort, and enhance comfort of use.

[0109] By co-loading oil-control peptides, oil-control ingredients or anti-inflammatory ingredients into liposomes to prepare liposome hydrogel preparations and performing surface modification, the stability, bioavailability and therapeutic effects of the active ingredients can be significantly improved while reducing side effects and toxicity.

[0110] Specifically, the liposome hydrogel prepared by the method is used as a sebum secretion inhibiting agent.

[0111] Embodiment 3

[0112] This animal experiment example is used to verify the effect of the liposomes encapsulating the target active ingredient prepared in Example 1.

[0113] Experimental method: 24 male golden rats (8 weeks old) were used. After removing the hair on their backs, 0.5ml to 2ml of liposomes encapsulating the target active ingredient were applied to the sebaceous glands on both sides of the exposed sides, and gently massaged until absorbed. Repeated 7 times a week, and the modeling time was 4 weeks. According to whether the liposome drug encapsulating the target active ingredient was injected, it was divided into a "control group", "free active ingredient group" and "experimental group". The "experimental group" was further divided into a "low-dose group" (0.5ml / kg mouse weight), a "high-dose group" (1.0ml / kg mouse weight), and a "liposome hydrogel preparation group" (1.0ml / kg mouse weight).

[0114] Experimental results:

[0115] Each group of golden hamsters was treated with different preparations for 30 days according to the above experimental method. It can be seen that: Day 0: the initial size of the sebaceous gland spot area of ​​each group; Day 7: the change in the sebaceous gland spot area began to show; Day 15: the changes between the groups became more obvious; Day 30: the final result, the difference between the groups was significant. The sebaceous gland spot area of ​​the "control group" and the "free active ingredient group" gradually increased over time, and the cumulative growth rate in 30 days was 22.25% and 18.34% respectively, while the sebaceous gland spot area of ​​the "low-dose group", "medium-dose group" and "liposome hydrogel preparation group" gradually decreased within 30 days, decreasing by 12.33%, 18.52% and 21.62% respectively. The experimental results show that the oil-control peptide has a significant effect on inhibiting the synthesis of sebum in the sebaceous glands, indicating that the oil-control peptide has the effect of inhibiting the synthesis of sebum in the sebaceous glands of golden hamsters. Compared with the free active ingredients, the liposome hydrogel preparation group showed a stronger effect of inhibiting sebum synthesis, which shows that the liposome hydrogel has good skin permeability and can deliver the oil-control peptide more effectively. Both the medium-dose group and the low-dose group showed an oil-control effect, but the medium-dose group had a better effect, and the liposome hydrogel preparation group had the best effect, indicating that the oil-control effect is dose-dependent. The area of ​​sebaceous gland spots in the control group and the free active ingredient group increased, indicating that the use of free active ingredients alone is not significant, and the delivery of active ingredients through liposome hydrogels can significantly improve the therapeutic effect.

[0116] The technical solution of the embodiment of the present invention is to combine a drug (oil-controlling peptide or oil-controlling component or anti-inflammatory component) with a targeted liposome to construct a targeted liposome encapsulating an oil-controlling peptide or oil-controlling component or anti-inflammatory component drug, and to precisely control the ratio of cholesterol, phospholipids and lipids, and to hydrate the lipid membrane using a buffer containing the target active ingredient, and to perform ultrasonic treatment and small-pore membrane extrusion technology, and to remove the free target active ingredient by dialysis, and to optimize the particle size and uniformity of the secondary liposome, so as to improve the encapsulation rate and distribution uniformity of the liposome, and to make the process simple and convenient, and the hydrogel has high stability. Note that the above are only preferred embodiments of the present invention and the technical principles used. Those skilled in the art will understand that the present invention is not limited to the specific embodiments described herein, and that various obvious changes, readjustments and substitutions can be made to those skilled in the art without departing from the scope of protection of the present invention. Therefore, although the present invention is described in more detail by the above embodiments, the present invention is not limited to the above embodiments, and may include more other equivalent embodiments without departing from the concept of the present invention, and the scope of the present invention is determined by the scope of the appended claims.

Claims

1. A method for preparing a liposome hydrogel, characterized in that: The steps include: preparing liposomes; co-loading a target active ingredient into the liposome; removing the free target active ingredient in the liposome; The liposomes are characterized by morphology, including scanning electron microscopy, particle size determination, transmission electron microscopy, dynamic light scattering, and stability; The liposome is added into a gel solution to form a liposome hydrogel preparation, and the surface of the liposome is modified.

2. The method for preparing the liposome hydrogel according to claim 1, characterized in that: include: The target active ingredient is any one of the structures of oil-controlling peptide, oil-controlling ingredient or anti-inflammatory ingredient.

3. The method for preparing the liposome hydrogel according to claim 2, characterized in that: The method for preparing liposomes comprises: 7 parts by weight of phospholipid, 2 parts by weight of cholesterol, 1 part by weight of lipid, and 1 part by weight of polyvinyl alcohol are selected to form a membrane material; Add 10 mL to 20 mL of chloroform to the membrane material; The membrane material is subjected to a first ultrasonic treatment for 5-10 minutes, the ultrasonic frequency is adjusted to 20-40 kHz, and the power is set to 20-30, so that the membrane material is fully dissolved in the chloroform to form a chloroform solution; The chloroform solution is placed in a vacuum environment to evaporate the chloroform to form liposomes.

4. The method for preparing the liposome hydrogel according to claim 3, characterized in that: The method of placing the chloroform solution in a vacuum environment to evaporate the chloroform to form liposomes comprises: The chloroform solution is transferred to an evaporating bottle of a rotary evaporator, the rotation speed is set to 100 to 200 rpm, the rotation temperature is set to 40 to 50° C., and the evaporation of chloroform is accelerated by heating and rotation; The chloroform solution is subjected to vacuum treatment to maintain the pressure in the evaporating flask below 10 to 20 kPa to accelerate the volatilization of chloroform; During the rotary evaporation process, liposomes gradually form from the container wall in the evaporation flask; After the chloroform is evaporated, uniform liposomes are obtained, and the liposomes appear as transparent or milky white films.

5. The method for preparing the liposome hydrogel according to claim 4, characterized in that: The method of co-loading the target active ingredient into the liposome comprises: Take sodium dihydrogen phosphate and disodium hydrogen phosphate, dissolve them in deionized water, and adjust the pH value to 7.0 to 7.4 to form a buffer; adding oil-controlling peptides or oil-controlling ingredients or anti-inflammatory ingredients to the buffer; Hydrate the lipid membrane with a buffer containing the oil-control peptide or oil-control component or anti-inflammatory component; The hydrated liposomes having the oil-controlling peptide or oil-controlling component or anti-inflammatory component are placed in a tube; The hydrated liposomes are subjected to a second ultrasonic treatment, the ultrasonic treatment time is 5 to 10 minutes, the frequency is 20 kHz to 40 kHz, and the power is adjusted to 30% to 40%; Transferring the ultrasonically treated liposome suspension to a membrane filtration device with a small pore size of 100 nm to 500 nm; The liposomes are squeezed through a membrane with a small pore size, and the oil-controlling peptide or oil-controlling component or anti-inflammatory component is effectively encapsulated in the liposomes to obtain uniformly distributed liposomes with the oil-controlling peptide or oil-controlling component or anti-inflammatory component.

6. The method for preparing the liposome hydrogel according to claim 5, characterized in that: The method for removing the free target active ingredient in the liposome comprises: Taking the prepared liposomes having the target active ingredient, adding them to the emulsion solution to form a liposome solution; The liposome solution is added to the activated dialysis bag and allowed to sink for 7 to 12 hours to remove the unencapsulated target active ingredient.

7. The method for preparing the liposome hydrogel according to claim 6, characterized in that: The liposomes are characterized by morphology, including scanning electron microscopy, particle size determination, transmission electron microscopy, dynamic light scattering, and stability. The characterization methods include: Electron microscopy: drop the liposome solution onto a conductive sample support, and after drying, use a scanning electron microscope to observe the surface morphology of the sample; Particle size determination: using a laser particle size analyzer to measure the average particle size and particle size distribution of the liposomes to evaluate the particle size and distribution uniformity of the liposomes; Transmission electron microscopy, using dynamic light scattering technology to calculate the width of the liposome size distribution, the smaller the PDI value, the narrower the distribution and the better the particle uniformity; Dynamic light scattering: the liposome solution is dropped onto a carbon film, and a transmission electron microscope is used to observe the internal structure of the sample to observe the internal structure of the liposome, the thickness of the membrane, and the membrane stacking.

8. The method for preparing the liposome hydrogel according to claim 7, characterized in that: The liposomes are characterized by morphology, including scanning electron microscopy, particle size, PDI, Zeta potential, transmission electron microscopy, in vitro release performance, storage stability, in vitro and in vivo uptake, and cytotoxicity. The method also includes: The storage stability of the liposomes was tested, LRn represented the leakage rate at the nth month, C0 represented the oil-control peptide concentration at the initial time point (0 months), and Cn represented the oil-control peptide concentration at the nth month. The calculation formula for calculating the leakage rate of the free oil-control peptide removed from the liposomes was:

9. The method for preparing the liposome hydrogel according to claim 8, characterized in that: The method of adding the liposome into a gel solution to form a liposome hydrogel preparation and modifying the surface of the liposome comprises: Slowly adding the liposomes into the gel solution and stirring evenly to make the liposomes evenly dispersed in the gel matrix to form a liposome hydrogel preparation; The PEG with active groups at the end of the liposome is coupled with the phospholipids on the surface of the liposome through chemical reaction.

10. The method for preparing the liposome hydrogel according to any one of claims 1 to 9, characterized in that: The liposome hydrogel prepared by the method is used as a sebum secretion inhibiting agent.

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