Dermal filler and preparation method thereof

Abstract

The present invention provides a dermal filler and a preparation method thereof, relating to the field of biomedicine. The dermal filler comprises a filler solution and polylactic acid / hydroxyethyl cellulose microspheres dispersed in the filler solution; the filler solution comprises a suspending dispersant and a buffer salt; and the polylactic acid / hydroxyethyl cellulose microspheres comprise polylactic acid microspheres and hydroxyethyl cellulose coated on the surface of the polylactic acid microspheres. The dermal filler provided by the present invention, which comprises polylactic acid / hydroxyethyl cellulose microspheres as its primary component and supplemented with a filler solution, exhibits excellent biocompatibility and can provide a long-lasting filling effect, thus achieving efficacy without the need for multiple injections and being easy to use.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a dermal filler and a preparation method thereof. Background Art

[0002] Dermal fillers refer to a type of material that is implanted under the skin or into the dermis to change or correct skin soft tissue. They are used to replace tissue lost due to disease, trauma, etc. or for medical cosmetic purposes. Existing dermal fillers are mostly used to fill wrinkles and folds in the skin, replacing the loss of skin soft tissue caused by disease or skin aging.

[0003] Currently, there are many dermal filler products on the market, which can be divided into two categories based on their mode of action: the first category provides a filling effect through volume, such as cross-linked hyaluronic acid, collagen and other fillers; this type of filler has a short degradation time in the body and cannot provide long-term filling effects, requiring repeated injections. In addition, fillers with cross-linked hyaluronic acid as the main component have a certain amount of cross-linker residue due to the use of chemical cross-linking agents, which may cause a risk of biotoxicity. Furthermore, fillers composed of single cross-linked hyaluronic acid have poor fluidity and greater resistance during injection; the second type of filler can stimulate the body's own collagen regeneration to play a filling role, and includes high-molecular synthetic polymers such as poly (L-lactic acid), polycaprolactone and hydroxyapatite; this type of filler mainly stimulates the body's own collagen regeneration through degradation products to exert a filling effect, and the material degradation requires a certain amount of time, so it cannot produce an immediate filling effect. Due to individual differences, different patients have different sensitivities to stimuli, and excessive stimulation can easily cause the skin filling effect to meet expectations.

[0004] Existing absorbable injectable skin fillers are mainly sodium hyaluronate (cross-linked or non-cross-linked), poly-L-lactic acid and collagen. Among them, sodium hyaluronate cross-linking technology is mature. A common method is to cross-link it using chemical cross-linkers such as divinyl sulfone (DVS) or butanediol diglycidyl ether (BDDE), and to control its in vivo retention time by adjusting the degree of cross-linking. Specifically, patent CN108395552 addresses the problems of poor product uniformity and difficult canning of sodium hyaluronate gel products by varying the degree of cross-linking between hyaluronic acid and chemical cross-linkers, thereby affecting its rheological properties and changing the size of the final gel particles. Patent CN113278170A utilizes the properties of long-chain polysaccharide hyaluronic acid, which has higher degrees of freedom and can expose more reactive groups in lithium bromide solution, to mix sodium hyaluronate with lithium bromide to improve the uniformity of the cross-linking reaction, cross-linking efficiency, and product recovery rate. However, hyaluronic acid suffers from poor stability, sensitivity to hyaluronidase and free radicals, and short in vivo retention time. Even using cross-linking agents to regulate in vivo retention time cannot solve the problems of high injection frequency and high cost.

[0005] Collagen is a biopolymer substance widely present in the mammalian body. It is an important component of connective tissue and extracellular matrix. It has good biological activity and is a good biological filling material. However, it degrades quickly, has a short retention time, and has poor biological stability. Multiple fillings are required to achieve a lasting filling effect.

[0006] Currently, poly(L-lactic acid) skin fillers have shortcomings such as long hydration time, subcutaneous nodules after injection, and instability of poly(L-lactic acid). At the same time, fillers such as poly(lactic acid) used alone to stimulate autologous fibroblasts to form collagen do not have a good filling effect in a short period of time. Therefore, sodium hyaluronate or substances (such as cross-linked dextran, amino acids, etc.) are often added to poly(L-lactic acid) materials to ensure the filling effect while increasing the durability of the filling effect. However, the filling effect of such products varies from person to person, and the effect of the same injection dose may differ greatly from expectations. Excessive injection doses may also cause inflammation and form tissue cysts, requiring multiple injections to be effective.

[0007] Therefore, existing absorbable injectable skin fillers require multiple injections to be effective, which is inconvenient to use. Summary of the Invention

[0008] The technical problem solved by the present invention is that existing absorbable injectable skin fillers require multiple injections to be effective.

[0009] To solve the above problems, the present invention provides a dermal filler, comprising a filler solution and polylactic acid / hydroxyethyl cellulose microspheres dispersed in the filler solution; the mass content of the polylactic acid / hydroxyethyl cellulose microspheres in the filler solution is 10%-60%; the filler solution comprises a suspending dispersant and a buffer salt; the buffer salt is a phosphate; the polylactic acid / hydroxyethyl cellulose microspheres comprise polylactic acid microspheres and hydroxyethyl cellulose coated on the surface of the polylactic acid microspheres; in the polylactic acid / hydroxyethyl cellulose microspheres, the mass ratio of the polylactic acid microspheres to the hydroxyethyl cellulose is 1:1 to 1:10.

[0010] Optionally, the suspending and dispersing agent is selected from at least one of hyaluronic acid, cellulose derivatives, and collagen.

[0011] Optionally, the filling solution further comprises a functional component; the functional component is selected from at least one of an anesthetic, an antioxidant, a mineral salt, and an amino acid.

[0012] Optionally, the mass ratio of the suspending dispersant, the functional component and the buffer salt in the filling liquid is (5-7): (1-2): (20-30).

[0013] Another object of the present invention is to provide a method for preparing the dermal filler as described above, comprising the following steps:

[0014] S1: emulsifying polylactic acid to obtain a polylactic acid microsphere suspension;

[0015] S2: freeze-drying the polylactic acid microsphere suspension, wherein the freeze-drying conditions are: pre-freezing at -40°C for 2 hours, and after the sample is frozen, freeze-drying for 36 hours to obtain polylactic acid microspheres;

[0016] S3: dissolving hydroxyethyl cellulose in a mixed solvent of acetone / water to prepare a coating solution containing hydroxyethyl cellulose;

[0017] S4: coating the polylactic acid microspheres with the coating liquid through a fluidized bed device to obtain coated microspheres;

[0018] S5: adding the coated microspheres to purified water for swelling, filtering, collecting the filtrate and irradiating the filtrate to obtain polylactic acid / hydroxyethyl cellulose microspheres;

[0019] S6: Compounding the polylactic acid / hydroxyethyl cellulose microspheres with a filling solution, packaging the mixture, and sterilizing the mixture with moist heat to obtain the dermal filler.

[0020] Optionally, step S1 includes:

[0021] S11: adding the polylactic acid into a first solvent, stirring and dissolving the polylactic acid to obtain a polylactic acid solution;

[0022] S12: Turn on the homogenizer and drop the polylactic acid solution into the second solvent. The speed of the homogenizer is 7000-15000 rpm. Emulsification is continued for 5-20 minutes under this condition. After emulsification is completed, stirring is continued for 3-12 hours to obtain a polylactic acid microsphere suspension.

[0023] Optionally, the first solvent and the second solvent are both selected from at least one of ethanol, acetone, ether, dichloromethane, chloroform, and purified water.

[0024] Optionally, the viscosity of the hydroxyethyl cellulose in step S3 is 800-4000 mPa.s (2%), and the degree of substitution is 1.6-3.0.

[0025] Optionally, the mass content of hydroxyethyl cellulose in the coating solution of step S3 is 0.5% to 5%.

[0026] Optionally, the coating conditions in step S4 are: fluidizing temperature 30°C to 50°C, blast flow rate 50L / min to 200L / min, jet pressure 0.1Mpa to 0.5Mpa, and liquid spray flow rate 1mL / min to 20mL / min; the coated microspheres are treated at 100°C to 160°C for 0.5h to 4h under inert gas protection.

[0027] Optionally, the irradiation dose of the irradiation treatment in step S5 is 5 kGy to 45 kGy.

[0028] Compared with the prior art, the dermal filler provided by the present invention has the following advantages:

[0029] The dermal filler provided by the present invention uses polylactic acid / hydroxyethyl cellulose microspheres as the main component and is supplemented with a filling liquid. It has good biocompatibility and can provide a long-lasting filling effect, so that it can be effective without the need for multiple injections and is easy to use. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a microscope photo of the polylactic acid / hydroxyethyl cellulose microspheres of the present invention. DETAILED DESCRIPTION

[0031] The following describes in detail embodiments of the present invention. Examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, and are not to be construed as limiting the present invention. All other embodiments obtained by persons of ordinary skill in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0032] To solve the problem that existing absorbable injectable dermal fillers require multiple injections to be effective, the present invention provides a dermal filler, which comprises a filler solution and polylactic acid / hydroxyethyl cellulose microspheres dispersed in the filler solution; wherein the mass content of the polylactic acid / hydroxyethyl cellulose microspheres in the filler solution is 10%-60%; the filler solution comprises a suspending dispersant and a buffer salt; in this application, the buffer salt is preferably a phosphate; see Figure 1 As shown, the polylactic acid / hydroxyethyl cellulose microspheres include polylactic acid microspheres and hydroxyethyl cellulose coated on the surface of the polylactic acid microspheres; in the polylactic acid / hydroxyethyl cellulose microspheres, the mass ratio of the polylactic acid microspheres to the hydroxyethyl cellulose is 1:1 to 1:10.

[0033] Among them, polylactic acid / hydroxyethyl cellulose microspheres form a stable gel wrapping on the surface of polylactic acid microspheres through hydroxyethyl cellulose. On the one hand, it can produce a timely filling effect. On the other hand, after being coated with hydroxyethyl cellulose, it can have a sustained-release effect, which helps to prolong the degradation time of polylactic acid and reduce its degradation rate, so that the degradation products can be gradually released to stimulate collagen production. At the same time, hydroxyethyl cellulose gradually degrades, and finally realizes the role of self-collagen replacing microspheres to play a role in tissue filling. Through the slow transition from physical filling to collagen regeneration, a natural filling effect is achieved, thereby realizing the conversion of dermal fillers from physical filling to autologous collagen filling, and then being able to exert a long-term filling effect through a single injection. It can take effect without multiple injections and is easy to use.

[0034] In addition, the polylactic acid / hydroxyethyl cellulose microspheres of the present invention have a small particle size, and the product is easy to inject without clogging the needle.

[0035] The dermal filler provided by the present invention uses polylactic acid / hydroxyethyl cellulose microspheres as the main component and is supplemented with a filling liquid. It has good biocompatibility and can provide a long-lasting filling effect, so that it can be effective without the need for multiple injections and is easy to use.

[0036] The preferred suspending and dispersing agent of the present invention is selected from at least one of hyaluronic acid, cellulose derivatives, and collagen, so that the gel wrapping formed by hydroxyethyl cellulose on the surface of polylactic acid microspheres can cooperate with the gel suspending and dispersing agent. The superposition effect of the two is more conducive to producing a timely filling effect.

[0037] In addition, to ensure the filling effect, the filling liquid of the present invention preferably also includes a functional component; the functional component is selected from at least one of anesthetics, antioxidants, mineral salts, and amino acids, and the specific type can be determined according to the filling requirements.

[0038] The preferred mass ratio of the suspending and dispersing agent, the functional component and the buffer salt in the filling liquid of the present invention is (5-7): (1-2): (20-30).

[0039] Another object of the present invention is to provide a method for preparing the dermal filler as described above, the method comprising the following steps:

[0040] S1: emulsifying polylactic acid to obtain a polylactic acid microsphere suspension;

[0041] S2: freeze-drying the polylactic acid microsphere suspension. The freeze-drying conditions are: pre-freezing at -40°C for 2 hours, freezing the sample for 36 hours after freezing, and obtaining polylactic acid microspheres.

[0042] S3: dissolving hydroxyethyl cellulose in a mixed solvent of acetone / water to prepare a coating solution containing hydroxyethyl cellulose;

[0043] S4: coating the polylactic acid microspheres with the coating liquid through a fluidized bed device to obtain coated microspheres;

[0044] S5: adding the coated microspheres to purified water for swelling, filtering, collecting the filtrate and irradiating the filtrate to obtain polylactic acid / hydroxyethyl cellulose microspheres;

[0045] S6: Compounding the polylactic acid / hydroxyethyl cellulose microspheres with the filling solution, packaging the mixture and sterilizing it with moist heat to obtain a dermal filler.

[0046] The preparation method of the dermal filler provided by the present invention has a simple preparation process. The prepared dermal filler, which uses polylactic acid / hydroxyethyl cellulose microspheres as a main component and is supplemented with a filling liquid, has good biocompatibility and can provide a long-lasting filling effect, thereby being effective without the need for multiple injections and being easy to use.

[0047] Specifically, the preferred step S1 of the present invention includes:

[0048] S11: adding polylactic acid to the first solvent, stirring and dissolving, to obtain a polylactic acid solution;

[0049] S12: Turn on the homogenizer and drip the polylactic acid solution into the second solvent. The speed of the homogenizer is 7000-15000 rpm. Emulsification is continued for 5-20 minutes under this condition. After emulsification is completed, stirring is continued for 3-12 hours to obtain a polylactic acid microsphere suspension.

[0050] In the preferred step S12 of the present invention, the polylactic acid solution is slowly dripped into the second solvent at a rate of 5-20 mL / min.

[0051] The first solvent and the second solvent are both selected from at least one of ethanol, acetone, ether, dichloromethane, chloroform, and purified water; the first solvent and the second solvent may be the same or different.

[0052] To ensure that the dermal filler can simultaneously provide timely filling and long-lasting filling effects, the viscosity of the hydroxyethyl cellulose in step S3 is preferably 800-4000 mPa.s (2%), and the degree of substitution is preferably 1.6-3.0; and the mass content of the hydroxyethyl cellulose in the coating solution in step S3 is 0.5% to 5%.

[0053] Furthermore, the coating conditions in step S4 of the present invention are preferably as follows: fluidizing temperature 30°C to 50°C, blast flow rate 50L / min to 200L / min, jet pressure 0.1Mpa to 0.5Mpa, and liquid spray flow rate 1mL / min to 20mL / min; the coated microspheres are treated at 100°C to 160°C under inert gas protection for 0.5h to 4h.

[0054] In the present invention, it is further preferred that the irradiation dose in step S5 is 5 kGy to 45 kGy.

[0055] The polylactic acid microspheres in the present invention are coated with hydroxyethyl cellulose. After high-temperature treatment, the hydroxyethyl cellulose can form a stable coating on the surface of the microspheres, which has strong hydrophobicity and degradation resistance. After the microspheres absorb water and swell, they are subjected to radiation cross-linking treatment to further increase their stability and prolong the degradation time of the hydroxyethyl cellulose, thereby extending the action time of the filler in the body.

[0056] The present invention is the first to use cross-linked hydroxyethyl cellulose as a coating material to prepare polylactic acid composite microspheres. High-temperature treatment and irradiation are used to cross-link the hydroxyethyl cellulose, thereby extending its degradation time and stabilizing the coating layer. Ultimately, the degradation regulation of polylactic acid is achieved, causing it to degrade slowly and gradually stimulating autologous collagen regeneration.

[0057] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below.

[0058] Example 1

[0059] This embodiment provides a method for preparing a dermal filler, which specifically comprises the following steps:

[0060] S1: Add 10 g of polylactic acid to 60 mL of acetone and stir to dissolve. Then, start a homogenizer and slowly drip the polylactic acid solution into purified water at a rate of 8 mL / min. The homogenizer speed is 9000 rpm. Emulsification is continued under this condition for 10 minutes. After emulsification is completed, stirring is continued for 6 hours to obtain a polylactic acid microsphere suspension.

[0061] S2: freeze-drying the polylactic acid microsphere suspension to obtain polylactic acid microspheres;

[0062] S3: dissolving hydroxyethyl cellulose (viscosity of 2000 mPa.s (2%), degree of substitution of 1.7) in a mixed solvent of acetone / water to prepare a coating solution containing 1% by weight of hydroxyethyl cellulose;

[0063] S4: Coating the polylactic acid microspheres with the coating liquid using a fluidized bed apparatus, with the coating conditions being: fluidization temperature of 35°C, air flow rate of 80 L / min, jet pressure of 0.2 MPa, and liquid spray rate of 8 ml / min; and treating the coated microspheres at 125°C for 1 h under nitrogen protection to obtain coated microspheres;

[0064] S5: adding the coated microspheres to purified water and swelling them for 26 hours. After filtering, the filtrate was collected and irradiated at a dose of 15 kGy to obtain polylactic acid / hydroxyethyl cellulose microspheres;

[0065] S6: Dissolve polylactic acid / hydroxyethyl cellulose microspheres and 10 g of hyaluronic acid in a buffered saline solution prepared with water for injection. Sterilize the solution by wet heat sterilization at 121°C for 15 min after aliquoting to obtain a dermal filler.

[0066] Example 2

[0067] This embodiment provides a method for preparing a dermal filler, which specifically comprises the following steps:

[0068] S1: Add 10 g of polylactic acid to 70 mL of dichloromethane and stir to dissolve. Then, start a homogenizer and slowly drip the polylactic acid solution into purified water at a rate of 12 mL / min. The homogenizer speed is 12000 rpm. Emulsification is continued under this condition for 10 minutes. After emulsification is completed, stirring is continued for 12 hours to obtain a polylactic acid microsphere suspension.

[0069] S2: freeze-drying the polylactic acid microsphere suspension to obtain polylactic acid microspheres;

[0070] S3: dissolving hydroxyethyl cellulose (3000 mPa.s (2%), degree of substitution 2.0) in a mixed solvent of acetone / water to prepare a coating solution containing 1% by weight of hydroxyethyl cellulose;

[0071] S4: Coating the polylactic acid microspheres with the coating liquid using a fluidized bed apparatus, with the following coating conditions: fluidization temperature 40°C, blast flow rate 120 L / min, jet pressure 0.3 MPa, and spray flow rate 10 ml / min; treating the coated microspheres at 140°C for 2 h under nitrogen protection to obtain coated microspheres;

[0072] S5: adding the coated microspheres to purified water and swelling them for 52 hours. After filtering, the filtrate was collected and irradiated at a dose of 25 kGy to obtain polylactic acid / hydroxyethyl cellulose microspheres;

[0073] S6: Dissolve polylactic acid / hydroxyethyl cellulose microspheres and 10 g of hydroxyethyl cellulose in a buffered saline solution prepared with water for injection. Sterilize the solution by wet heat sterilization at 121°C for 15 min to obtain a dermal filler.

[0074] Example 3

[0075] This embodiment provides a method for preparing a dermal filler, which specifically comprises the following steps:

[0076] S1: Add 10 g of polylactic acid to 60 mL of ether and stir to dissolve. Then, start a homogenizer and slowly drip the polylactic acid solution into purified water at a rate of 20 mL / min. The homogenizer speed is 15,000 rpm. Emulsification is continued under this condition for 20 minutes. After emulsification is completed, stirring is continued for 3 hours to obtain a polylactic acid microsphere suspension.

[0077] S2: freeze-drying the polylactic acid microsphere suspension to obtain polylactic acid microspheres;

[0078] S3: dissolving hydroxyethyl cellulose (3500 mPa.s (2%), degree of substitution 2.3) in a mixed solvent of acetone / water to prepare a coating solution containing 5% by weight of hydroxyethyl cellulose;

[0079] S4: Coating the polylactic acid microspheres with the coating liquid using a fluidized bed apparatus, with the coating conditions being: fluidization temperature 50°C, blast flow rate 200 L / min, jet pressure 0.5 MPa, and spray flow rate 20 ml / min; the coated microspheres were subjected to a high-temperature treatment at 160°C for 4 h under nitrogen protection to obtain coated microspheres;

[0080] S5: adding the coated microspheres to purified water and swelling them for 26 hours. After filtering, the filtrate was collected and irradiated at a dose of 45 kGy to obtain polylactic acid / hydroxyethyl cellulose microspheres;

[0081] S6: Dissolve polylactic acid / hydroxyethyl cellulose microspheres and 10 g of hyaluronic acid in a buffered saline solution prepared with water for injection. Sterilize the solution by wet heat sterilization at 121°C for 15 min after aliquoting to obtain a dermal filler.

[0082] Comparative Example 1

[0083] This embodiment provides a method for preparing a dermal filler, which specifically comprises the following steps:

[0084] S1: Add 10 g of polylactic acid to 60 mL of acetone and stir to dissolve. Then, start a homogenizer and slowly drip the polylactic acid solution into purified water at a rate of 8 mL / min. The homogenizer speed is 9000 rpm. Emulsification is continued under this condition for 10 minutes. After emulsification is completed, stirring is continued for 6 hours to obtain a polylactic acid microsphere suspension.

[0085] S2: freeze-drying the polylactic acid microsphere suspension to obtain polylactic acid microspheres;

[0086] S3: Dissolve polylactic acid microspheres and 10 g of hyaluronic acid in a buffered saline solution prepared with water for injection. After packaging, sterilize with wet heat at 121°C for 15 min to obtain a dermal filler.

[0087] The difference between this comparative example and Example 1 is that the coating operation is removed and only polylactic acid microspheres are compounded to form the filler.

[0088] Test example: Performance testing of dermal fillers

[0089] The dermal fillers provided in the above examples and comparative examples were subjected to in vitro degradation and cytotoxicity tests:

[0090] In vitro degradation time test method:

[0091] Weigh 2.0 g of sample respectively into 50 mL of 0.9% saline, place in a 37°C constant temperature shaker for shaking, take samples regularly to weigh the gel mass and replace the saline, and record the complete degradation time of the sample.

[0092] Cytotoxicity test method:

[0093] Weigh 1.0 g of each sample into 50 mL of cell culture medium and shake at 37°C for 24 hours to prepare the extract. The test solution is the extract obtained by centrifugation and the supernatant is collected. Tests were performed using mouse fibroblast L929 cells according to the MTT cytotoxicity test in accordance with the national standard GB / T16886.5-2017, Biological Evaluation of Medical Devices, Part 5, In Vitro Cytotoxicity Tests.

[0094] The test results are shown in Table 1:

[0095] Table 1

[0096] Serial number Degradation time Survival rate Example 1 185d 91.5％ Example 2 240d 95.0％ Example 3 280d 92.8％ Comparative Example 1 122d 85.6％

[0097] As can be seen from the results in Table 1, compared with the blank control group, the cell viability of the sample groups of Examples 1-3 of the present invention and Comparative Example 1 were 91.5%, 95.0%, 92.8% and 85.6%, respectively. The prepared fillers had good biocompatibility and no potential cytotoxicity.

[0098] The above test data show that the dermal filler provided by the present invention can produce a filling effect in a timely manner. At the same time, the filling effect is long-lasting. A single injection can produce a long-term filling effect. It can be effective without the need for multiple injections and is easy to use.

[0099] Although the present disclosure is disclosed as above, the protection scope of the present disclosure is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present disclosure, and these changes and modifications will fall within the protection scope of the present invention.

Claims

1. A dermal filler, characterized in that: The invention comprises a filling liquid and polylactic acid / hydroxyethyl cellulose microspheres dispersed in the filling liquid; the mass content of the polylactic acid / hydroxyethyl cellulose microspheres in the filling liquid is 10% to 60%; the filling liquid comprises a suspending dispersant and a buffer salt; the buffer salt is phosphate; the polylactic acid / hydroxyethyl cellulose microspheres comprise polylactic acid microspheres and hydroxyethyl cellulose coated on the surface of the polylactic acid microspheres; in the polylactic acid / hydroxyethyl cellulose microspheres, the mass ratio of the polylactic acid microspheres to the hydroxyethyl cellulose is 1:1 to 1:

10.

2. The dermal filler according to claim 1, wherein: The suspending and dispersing agent is selected from at least one of hyaluronic acid, cellulose derivatives, and collagen.

3. The dermal filler according to claim 1, wherein The filling solution further comprises a functional component; the functional component is selected from at least one of an anesthetic, an antioxidant, a mineral salt, and an amino acid.

4. The dermal filler according to claim 3, wherein The mass ratio of the suspending dispersant, the functional component and the buffer salt in the filling liquid is (5-7): (1-2): (20-30).

5. A method for preparing a dermal filler according to any one of claims 1 to 4, characterized in that: The steps include: S1: emulsifying polylactic acid to obtain a polylactic acid microsphere suspension; S2: freeze-drying the polylactic acid microsphere suspension, wherein the freeze-drying conditions are: pre-freezing at -40°C for 2 hours, and after the sample is frozen, freeze-drying for 36 hours to obtain polylactic acid microspheres; S3: dissolving hydroxyethyl cellulose in a mixed solvent of acetone / water to prepare a coating solution containing hydroxyethyl cellulose; S4: coating the polylactic acid microspheres with the coating liquid through a fluidized bed device to obtain coated microspheres; S5: adding the coated microspheres to purified water for swelling, filtering, collecting the filtrate and irradiating the filtrate to obtain polylactic acid / hydroxyethyl cellulose microspheres; S6: Compounding the polylactic acid / hydroxyethyl cellulose microspheres with a filling solution, packaging the mixture, and sterilizing the mixture with moist heat to obtain the dermal filler.

6. The method for preparing a dermal filler according to claim 5, wherein: Step S1 includes: S11: adding the polylactic acid into a first solvent, stirring and dissolving the polylactic acid to obtain a polylactic acid solution; S12: Turn on the homogenizer and drop the polylactic acid solution into the second solvent. The speed of the homogenizer is 7000-15000 rpm. Emulsification is continued for 5-20 minutes under this condition. After emulsification is completed, stirring is continued for 3-12 hours to obtain a polylactic acid microsphere suspension.

7. The method for preparing a dermal filler according to claim 6, wherein: The first solvent is selected from at least one of ethanol, acetone, ether, dichloromethane, and chloroform, and the second solvent is selected from at least one of ethanol, acetone, ether, dichloromethane, chloroform, and purified water.

8. The method for preparing a dermal filler according to claim 5, wherein: In step S3, the viscosity of the 2% hydroxyethyl cellulose is 800-4000 mPa·s, and the degree of substitution is 1.6-3.

0.

9. The method for preparing a dermal filler according to claim 5, wherein: The mass content of hydroxyethyl cellulose in the coating solution of step S3 is 0.5% to 5%.

10. The method for preparing a dermal filler according to claim 5, wherein: The coating conditions in step S4 are: fluidization temperature 30°C to 50°C, blast flow rate 50L / min to 200L / min, jet pressure 0.1Mpa to 0.5Mpa, and spray flow rate 1mL / min to 20mL / min; the coated microspheres are treated at 100°C to 160°C under inert gas protection for 0.5h to 4h.

11. The method for preparing a dermal filler according to claim 5, wherein: The irradiation dose of the irradiation treatment in step S5 is 5 kGy to 45 kGy.

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