Preparation method of face filling agent

Abstract

The invention belongs to the technical field of biomedical treatment, and particularly relates to a preparation method of a facial filling agent. Comprising the following steps: (1) mixing agarose with a first part of phosphate buffer solution, stirring until the agarose is completely dissolved, and cooling to obtain agarose gel; (2) mixing a nucleotide substance with a second part of phosphate buffer solution to obtain a nucleotide substance solution; (3) mixing lidocaine hydrochloride with a third part of the phosphate buffer solution to obtain a lidocaine hydrochloride solution; and (4) granulating the agarose gel through a screen, mixing the granulated agarose gel with a nucleotide substance solution and a lidocaine hydrochloride solution, defoaming, filling, and carrying out irradiation sterilization to obtain the facial filling agent. According to the preparation method, by integrating the percolation threshold response characteristic of agarose, the biological activity function of nucleotide substances and the anesthetic efficacy of lidocaine hydrochloride and combining scientific proportioning and process optimization, the innovative medical beauty filler with safety, functionality and clinical practicability is formed.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technology, and particularly relates to a preparation method of a facial filler. Background Art

[0002] Reducing the risk of embolism is a key safety consideration in aesthetic filler injections. Due to its unique physical and chemical properties, agarose filler shows certain advantages in reducing the risk of embolism. Agarose, a natural polysaccharide extracted from seaweed, has high biocompatibility and can be slowly degraded by the human body, usually lasting for 6 - 24 months, which greatly reduces the risk of long-term foreign body reactions. The "percolation threshold response characteristic" of agarose gel is particularly unique, and its physical state exhibits significant phase transition behavior with changes in concentration. When the concentration exceeds the critical value (percolation threshold), the intermolecular cross-linking effect is enhanced, forming a stable three-dimensional network structure, showing the characteristics of a solid gel; when the concentration is below this threshold, the cross-linked network dissociates, undergoes a phase transition, and transforms into a freely flowing liquid state. Based on this dynamic and reversible phase transition mechanism, in response to embolism complications, sufficient normal saline is locally perfused to dilute the gel system, so that the environmental concentration breaks through the percolation threshold critical point, thereby promoting the depolymerization and dispersion of the gel network at the embolism site and achieving non-invasive removal of the embolism.

[0003] In addition, nucleotide substances (PDRN / PN) as another key component, the deoxyribonucleotide fragments contained therein (such as those extracted from salmon DNA) can activate the adenosine A2A receptor in cells, stimulate the proliferation of fibroblasts, and accelerate the repair of damaged tissues. This process continuously promotes the synthesis of type I, type III collagen and elastin, effectively improving the elasticity and firmness of the skin. The effect usually becomes significant after 2 - 3 months and can be maintained for 6 - 12 months. At the same time, the three-dimensional support structure of PDRN / PN also provides space for the regeneration of the extracellular matrix and can temporarily improve wrinkles during volume maintenance.

[0004] Lidocaine hydrochloride, as a local anesthetic, is widely used in medical surgeries to relieve or eliminate pain. Its mechanism of action is mainly to block sodium channels on nerve fibers, reduce the conduction of nerve impulses, and thus achieve the effect of local anesthesia. Clinically, lidocaine hydrochloride is commonly used for surface anesthesia of the skin and mucous membranes and nerve block anesthesia. In addition, due to its anti-arrhythmic effect on the heart, it is also used to treat certain types of arrhythmias. When the dose is properly controlled, lidocaine hydrochloride is a safe and effective local anesthetic.

[0005] However, although existing medical aesthetic fillers have achieved certain results in improving skin condition, there are still some deficiencies in terms of safety, biocompatibility, and embolism risk control. Therefore, it is particularly important to develop a medical aesthetic filler that can significantly reduce the embolism risk, improve biocompatibility, and enhance safety. Summary of the Invention

[0006] Aiming at the deficiencies of the existing technology, the purpose of the present invention is to provide a preparation method of a facial filler. By integrating the percolation threshold response characteristics of agarose, the bioactive functions of nucleotide substances, and the anesthetic efficacy of lidocaine hydrochloride, combined with scientific ratio and process optimization, an innovative medical aesthetic filler with safety, functionality, and clinical practicability is formed.

[0007] The technical solutions adopted by the present invention are as follows: The facial filler described above comprises the following raw materials in parts by weight: Agarose: 1 - 5 parts; Nucleotide substances: 0.2 - 1.5 parts; Lidocaine hydrochloride: 0.1 - 0.5 parts; Phosphate buffer solution: 90 - 100 parts; The nucleotide substances are polydeoxyribonucleotide (PDRN) or polynucleotide (PN); The preparation method of the facial filler described above comprises the following steps: (1) Mix agarose with the first part of the phosphate buffer solution, heat it up to 80 - 90 °C, stir until the agarose is completely dissolved, then stop stirring and lower the system temperature to 0 - 35 °C to obtain agarose gel; (2) Mix the nucleotide substances with the second part of the phosphate buffer solution, stir and dissolve to obtain a nucleotide substances solution; (3) Mix lidocaine hydrochloride with the third part of the phosphate buffer solution, stir and dissolve to obtain a lidocaine hydrochloride solution; (4) After granulating the agarose gel through a 60 - mesh sieve, mix and stir it with the nucleotide substances solution and the lidocaine hydrochloride solution, perform vacuum degassing treatment, then fill it into a pre - filled syringe and irradiate for sterilization. The irradiation dose is 20 - 25 kGy, and finally, the facial filler is obtained.

[0008] The phosphate buffer solution is an isotonic phosphate buffer solution with a pH value of 6.8 - 7.3.

[0009] In the step (1) described above, the mass ratio of agarose to the first part of the phosphate buffer solution is 1:(12 - 60).

[0010] In the step (2), the mass ratio of the nucleotide substance to the second part of the phosphate buffer solution is 1:(20 - 150).

[0011] In the step (3), the mass ratio of lidocaine hydrochloride to the third part of the phosphate buffer solution is 0.3:(3 - 18).

[0012] In the present invention, there is a strong surface tension between individual agarose particles. After irradiation, the agarose particles are partially linked to the nucleotide substance through hydrogen bonds, greatly improving the hydration ability, reducing the friction force between the particles, and reducing the pushing force. Under the condition of embolism, a large amount of normal saline solution is usually injected. The water molecules in the normal saline solution can quickly dilute and replace the hydrogen bond link between the nucleotide substance and the agarose particles. Therefore, the addition of the nucleotide substance can not only increase the comfort during injection but also ensure the anti-embolism effect of the gel. At the same time, after PDRN is irradiated and sterilized, it is partially decomposed into single-stranded or short-chain deoxynucleotides (such as deoxyadenylic acid, deoxyguanylic acid, etc.) and deoxynucleosides (such as deoxyadenosine, deoxyguanosine, etc.). These substances can be used as raw materials for cell repair and nucleic acid synthesis, participate in DNA damage repair or energy metabolism, and provide instant nutrition for cell proliferation.

[0013] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The gel system constructed based on the agarose concentration-dependent phase transition characteristics in the present invention breaks through the limitation of the difficult post-treatment of traditional fillers after embolism. By precisely controlling the percolation threshold critical point, if vascular embolism occurs after injection, the reversible depolymerization of the gel network can be achieved by means of local normal saline perfusion, and the embolic substances can be removed without invasive surgical intervention. This characteristic not only greatly improves the clinical operation error tolerance rate but also reduces the risk of tissue necrosis caused by embolism. At the same time, the biodegradation period of agarose (6 - 24 months) matches the rhythm of human tissue repair, avoiding long-term foreign body reactions and further strengthening the safety basis of the material; (2) The present invention forms a dual construction system with complementary functions through polydeoxyribonucleotides or polynucleotides and agarose: the three-dimensional network of agarose provides physical support for the regeneration of the extracellular matrix, while polydeoxyribonucleotides or polynucleotides continuously stimulate collagen synthesis by activating adenosine A2A receptors. The two work together to achieve the dual effects of "instant filling + long-term repair". Among them, the bioactive components of polydeoxyribonucleotides or polynucleotides are gradually released within 2 - 3 months, promoting the continuous regeneration of type I, type III collagen and elastin, and making the filling effect transition from simple mechanical support to autologous tissue reconstruction, thereby extending the maintenance period of the cosmetic effect to 6 - 12 months, which is significantly better than the single-phase action mode of traditional fillers; (3)In the formulation of the present invention, lidocaine hydrochloride integrated through precise dosage control achieves effective local anesthesia while avoiding the risk of cardiovascular side effects. The standardized application of the phosphate buffer system ensures the pH stability and osmotic pressure balance of the gel. Combined with irradiation sterilization and vacuum degassing treatment, the final product has excellent biocompatibility and clinical stability. The direct filling design of the pre-filled syringe further reduces the possibility of secondary contamination and improves the convenience and safety of clinical use. Detailed implementation manners

[0014] The present invention will be further described below in conjunction with embodiments, but it does not limit the implementation of the present invention.

[0015] Unless otherwise specified, the raw materials used in the examples and comparative examples are all conventional commercially available raw materials, and the process methods used in the examples and comparative examples are all conventional methods in the art unless otherwise specified.

[0016] Some of the raw materials used in the examples and comparative examples are described as follows: Polydeoxyribonucleotide, purchased from Ruijiming (Shandong) Biotechnology Co., Ltd.; Polynucleotide, purchased from Ruijiming (Shandong) Biotechnology Co., Ltd.; The phosphate buffer solution is an isotonic phosphate buffer solution with a pH value of 7 ± 0.2, and its preparation method is as follows: Accurately weigh 7.5 g of sodium dihydrogen phosphate (NaH 2 PO 4 ), 33 g of disodium hydrogen phosphate (Na 2 HPO 4 ), and 1350 g of sodium chloride (NaCl) and add them to a clean liquid preparation tank. After adding an appropriate amount of deionized water for preliminary dissolution, continue to add deionized water until the total volume of the solution is 150 L, and fine-tune to the target pH range of 7 ± 0.2 by dropping dilute hydrochloric acid (HCl) or sodium hydroxide (NaOH) solution.

[0017] Example 1 The preparation method of the facial filler described above includes the following steps: (1) Mix 3 parts by weight of agarose with 60 parts by weight of the first part of the phosphate buffer solution, heat up to 90 °C, stir at a rotation speed of 500 rpm for 30 min until the agarose is completely dissolved, then stop stirring and lower the system temperature to 20 °C to obtain an agarose gel; (2) Mix 1 part by weight of polydeoxyribonucleotide (PDRN) with 30 parts by weight of the second part of the phosphate buffer solution, and stir at a rotation speed of 500 rpm for 60 min to obtain a nucleotide substance solution; (3) Mix 0.3 parts by weight of lidocaine hydrochloride with 6 parts by weight of phosphate buffer solution, and stir for 30 min under the condition of a rotation speed of 500 rpm to obtain a lidocaine hydrochloride solution; (4) After granulating the agarose gel through a 60-mesh sieve, mix and stir it with the nucleotide solution and the lidocaine hydrochloride solution. After vacuum degassing treatment, fill it into a pre-filled syringe, and perform irradiation sterilization after filling. The irradiation dose is 20 kGy to finally obtain a facial filler.

[0018] Example 2 The preparation method of the facial filler described above includes the following steps: (1) Mix 1 part by weight of agarose with 60 parts by weight of the first part of phosphate buffer solution, heat up to 90 °C, and stir for 30 min under the condition of a rotation speed of 500 rpm until the agarose is completely dissolved. Subsequently, stop stirring and lower the system temperature to 20 °C to obtain an agarose gel; (2) Mix 0.2 parts by weight of polydeoxyribonucleotide (PDRN) with 30 parts by weight of the second part of phosphate buffer solution, and stir for 60 min under the condition of a rotation speed of 500 rpm to obtain a nucleotide solution; (3) Mix 0.1 part by weight of lidocaine hydrochloride with 6 parts by weight of phosphate buffer solution, and stir for 30 min under the condition of a rotation speed of 500 rpm to obtain a lidocaine hydrochloride solution; (4) After granulating the agarose gel through a 60-mesh sieve, mix and stir it with the nucleotide solution and the lidocaine hydrochloride solution. After vacuum degassing treatment, fill it into a pre-filled syringe, and perform irradiation sterilization after filling. The irradiation dose is 20 kGy to finally obtain a facial filler.

[0019] Example 3 The preparation method of the facial filler described above includes the following steps: (1) Mix 5 parts by weight of agarose with 60 parts by weight of the first part of phosphate buffer solution, heat up to 90 °C, and stir for 30 min under the condition of a rotation speed of 500 rpm until the agarose is completely dissolved. Subsequently, stop stirring and lower the system temperature to 20 °C to obtain an agarose gel; (2) Mix 1.5 parts by weight of polydeoxyribonucleotide (PDRN) with 30 parts by weight of the second part of phosphate buffer solution, and stir for 60 min under the condition of a rotation speed of 500 rpm to obtain a nucleotide solution; (3) Mix 0.5 part by weight of lidocaine hydrochloride with 6 parts by weight of phosphate buffer solution, and stir for 30 min under the condition of a rotation speed of 500 rpm to obtain a lidocaine hydrochloride solution; (4) After granulating the agarose gel through a 60-mesh sieve, it is mixed and stirred with the nucleotide solution and the lidocaine hydrochloride solution. After vacuum degassing treatment, it is filled into a pre-filled syringe. After filling, it is irradiated and sterilized with a radiation dose of 20 kGy to finally obtain the facial filler.

[0020] Example 4 The preparation method of the described facial filler includes the following steps: (1) Mix 3 parts by weight of agarose with 60 parts by weight of the first part of phosphate buffer solution, heat up to 90 °C, and stir for 30 min at a rotation speed of 500 rpm until the agarose is completely dissolved. Subsequently, stop stirring and lower the system temperature to 20 °C to obtain the agarose gel; (2) Mix 1 part by weight of polynucleotide (PN) with 30 parts by weight of the second part of phosphate buffer solution, and stir for 60 min at a rotation speed of 500 rpm to obtain the nucleotide solution; (3) Mix 0.3 part by weight of lidocaine hydrochloride with 6 parts by weight of phosphate buffer solution, and stir for 30 min at a rotation speed of 500 rpm to obtain the lidocaine hydrochloride solution; (4) After granulating the agarose gel through a 60-mesh sieve, it is mixed and stirred with the nucleotide solution and the lidocaine hydrochloride solution. After vacuum degassing treatment, it is filled into a pre-filled syringe. After filling, it is irradiated and sterilized with a radiation dose of 20 kGy to finally obtain the facial filler.

[0021] Example 5 The preparation method of the described facial filler includes the following steps: (1) Mix 3 parts by weight of agarose with 60 parts by weight of the first part of phosphate buffer solution, heat up to 80 °C, and stir for 30 min at a rotation speed of 500 rpm until the agarose is completely dissolved. Subsequently, stop stirring and lower the system temperature to 0 °C to obtain the agarose gel; (2) Mix 1 part by weight of polydeoxyribonucleotide (PDRN) with 30 parts by weight of the second part of phosphate buffer solution, and stir for 60 min at a rotation speed of 500 rpm to obtain the nucleotide solution; (3) Mix 0.3 part by weight of lidocaine hydrochloride with 6 parts by weight of phosphate buffer solution, and stir for 30 min at a rotation speed of 500 rpm to obtain the lidocaine hydrochloride solution; (4) After granulating the agarose gel through a 60-mesh sieve, it is mixed and stirred with the nucleotide solution and the lidocaine hydrochloride solution. After vacuum degassing treatment, it is filled into a pre-filled syringe. After filling, it is irradiated and sterilized with a radiation dose of 20 kGy to finally obtain the facial filler.

[0022] Example 6 The preparation method of the facial filler comprises the following steps: (1) Mix 3 parts by weight of agarose with 60 parts by weight of the first part of phosphate buffer solution, heat up to 90°C, stir for 30 min at a rotation speed of 500 rpm until the agarose is completely dissolved, then stop stirring and lower the system temperature to 35°C to obtain agarose gel; (2) Mix 1 part by weight of polydeoxyribonucleotide (PDRN) with 30 parts by weight of the second part of phosphate buffer solution, stir for 60 min at a rotation speed of 500 rpm to obtain a nucleotide solution; (3) Mix 0.3 part by weight of lidocaine hydrochloride with 6 parts by weight of phosphate buffer solution, stir for 30 min at a rotation speed of 500 rpm to obtain a lidocaine hydrochloride solution; (4) After granulating the agarose gel through a 60-mesh sieve, mix and stir it with the nucleotide solution and the lidocaine hydrochloride solution, perform vacuum degassing treatment, then fill it into a pre-filled syringe, and perform irradiation sterilization after filling. The irradiation dose is 20 kGy, and finally a facial filler is obtained.

[0023] Example 7 The preparation method of the facial filler comprises the following steps: (1) Mix 3 parts by weight of agarose with 60 parts by weight of the first part of phosphate buffer solution, heat up to 90°C, stir for 30 min at a rotation speed of 500 rpm until the agarose is completely dissolved, then stop stirring and lower the system temperature to 20°C to obtain agarose gel; (2) Mix 1 part by weight of polydeoxyribonucleotide (PDRN) with 30 parts by weight of the second part of phosphate buffer solution, stir for 60 min at a rotation speed of 500 rpm to obtain a nucleotide solution; (3) Mix 0.3 part by weight of lidocaine hydrochloride with 6 parts by weight of phosphate buffer solution, stir for 30 min at a rotation speed of 500 rpm to obtain a lidocaine hydrochloride solution; (4) After granulating the agarose gel through a 60-mesh sieve, mix and stir it with the nucleotide solution and the lidocaine hydrochloride solution, perform vacuum degassing treatment, then fill it into a pre-filled syringe, and perform irradiation sterilization after filling. The irradiation dose is 25 kGy, and finally a facial filler is obtained.

[0024] Comparative Example 1 The difference from Example 1 is that the parts by weight of agarose is 0.5, and the others are the same as in Example 1.

[0025] Comparative Example 2 The difference from Example 1 is that the weight portion of agarose is 8, and the others are the same as in Example 1.

[0026] Comparative Example 3 The difference from Example 1 is that in step (4), after filling, moist heat sterilization is carried out, and the conditions of moist heat sterilization are: maintaining at 121 °C for 8 min, and the others are the same as in Example 1.

[0027] Comparative Example 4 The difference from Example 1 is that step (2) is not included, and the others are the same as in Example 1.

[0028] Comparative Example 5 The difference from Example 1 is that in step (1), the agarose is replaced with cross-linked sodium hyaluronate gel of the same weight portion; in step (4), after filling, moist heat sterilization (121 °C, 8 min) treatment is carried out; The preparation method of the cross-linked sodium hyaluronate gel is as follows: Weigh 2 g of sodium hyaluronate, place it in 10 mL of sodium hydroxide solution containing 0.1 mol of sodium hydroxide, fully dissolve it, add 0.2 g of 1,4-butanediol diglycidyl ether, react at 30 °C for 24 h, after the reaction is completed, take out the formed gel, cut it into blocks with a mass of 1 g, then, put the cut gel blocks into phosphate buffer solution to make them fully swell until the mass reaches 120 g. Finally, granulate the swollen gel through a 60-mesh sieve to obtain granular cross-linked sodium hyaluronate gel.

[0029] Comparative Example 6 The difference from Example 1 is that in step (1), the stirring temperature is 70 °C, and the others are the same as in Example 1.

[0030] Comparative Example 7 The difference from Example 1 is that in step (1), the stirring is stopped and the system temperature is reduced to -10 °C, and the others are the same as in Example 1.

[0031] Take the facial fillers finally obtained in Examples 1 to 7 and Comparative Examples 1 to 7 respectively for performance testing. The testing methods are as follows: Stability test: Take 20 portions of the facial fillers prepared in Examples 1 to 7 and Comparative Examples 1 to 7 respectively, put them into a stability test chamber, and place them at 75% humidity and 45 °C for 5 months, observe whether there is a layering phenomenon in the samples, and count the number of layered samples; Allergenicity: Test according to GB / T 16886.10-2017; Pushing force (N): Test with a universal testing machine at a temperature of 25 °C, a pushing speed of 30 mm / min, and a 2-mL disposable sterile syringe; Elastic modulus G′ (Pa): At 25 °C, rheological measurements were carried out using a rheometer; Anti-embolism effect: 1 mL of the facial fillers prepared in Examples 1 to 7 and Comparative Examples 1 to 7 was injected into an in vitro peripheral arterial vascular model to simulate the occurrence of embolism, and then 20 mL of normal saline was injected into the same site to observe the dredging condition of the vascular model.

[0032] The test results are shown in Table 1.

[0033] Table 1 Performance test results

[0034] From the test data in Table 1, it can be seen that for the facial fillers prepared in Examples 1 to 3, as the agarose content gradually increases, both the pushing force and the elastic modulus G′ show a gradually increasing trend. This phenomenon is mainly attributed to the excellent mechanical properties of agarose itself. In addition, the experimental results show that the change in the content of lidocaine hydrochloride has no significant effect on the product performance of this facial filler.

[0035] In Example 4, polynucleotide (PN) was used as a raw material. After detection, it was found that it had no obvious effect on the product performance of this facial filler.

[0036] In Examples 5 to 6, preparation was carried out by changing the gelation temperature conditions. The experimental data show that the change in the gelation temperature also has no obvious effect on the product performance of this facial filler.

[0037] In Example 7, the irradiation dose was increased to 25 kGy. The test results show that the pushing force of the product decreases, and the elastic modulus G′ also decreases accordingly. This is because the irradiation treatment will break the chemical bonds between agarose molecules, thereby leading to a decrease in the mechanical strength of the gel.

[0038] In Comparative Example 1, due to the low agarose content, the gelation performance of the gel was poor, which in turn led to insufficient gel stability and a significant decrease in mechanical properties.

[0039] In Comparative Example 2, the agarose content was too high, which directly led to an excessive pushing force, greatly reducing the comfort during injection. In addition, too high an agarose content will also have an adverse effect on the "percolation threshold response characteristics" of the agarose gel, thereby weakening its anti-embolism efficacy.

[0040] In Comparative Example 3, due to the use of moist heat sterilization, the gel melted again in the syringe and coagulated into lumps, so that it could not be smoothly pushed out for use.

[0041] In Comparative Example 4, compared with Example 1, polydeoxyribonucleotide (PDRN) was not added. In this case, a strong surface tension was exhibited between individual agarose particles, which directly led to a significant increase in the pushing force of the product. In Example 1, however, after irradiation, partial links were formed between the agarose particles and nucleotide substances through hydrogen bonds. This structure greatly enhanced the hydration ability, thereby effectively reducing the frictional force and pushing force between the particles. In addition, in the case where embolism might occur, when injecting a physiological saline solution, its water molecules could quickly dilute and replace the hydrogen bond links between the nucleotide substances and the agarose particles. Therefore, due to the lack of addition of nucleotide substances in Comparative Example 4, not only was the comfort during injection reduced, but also the anti-embolism effect of the gel was correspondingly weakened.

[0042] In Comparative Example 5, compared with Example 1, since the cross-linked sodium hyaluronate gel was used, it was difficult to effectively dredge it by perfusion and cleaning with physiological saline when embolism occurred; and due to the characteristics of the cross-linked sodium hyaluronate gel, only moist heat sterilization could be used, and this method could only partially change the molecular weight of PDRN and could not break its double helix structure. In contrast, Example 1 used irradiation sterilization, which could partially decompose PDRN into single-stranded or short-chain deoxynucleotides (such as deoxyadenylic acid, deoxyguanylic acid, etc.) and deoxynucleosides (such as deoxyadenosine, deoxyguanosine, etc.). These substances could be used as raw materials for cell repair and nucleic acid synthesis, participate in DNA damage repair or energy metabolism, and provide an immediate nutritional effect for cell proliferation.

[0043] In Comparative Example 6, the gelling temperature was relatively low, resulting in the failure to form a gel.

[0044] In Comparative Example 7, when the temperature dropped below the freezing point, part of the gel would precipitate, thus having an adverse effect on the stability of the product.

Claims

1. A method for preparing a facial filler, characterized in that: The facial filler comprises the following raw materials in parts by weight: Agarose: 1~5 parts; Nucleotide substances: 0.2~1.5 parts; Lidocaine hydrochloride: 0.1~0.5 parts; Phosphate buffer: 90~100 parts; The preparation method of the facial filler comprises the following steps: (1) Mixing agarose with the first part of phosphate buffer, heating to 80-90°C, stirring until the agarose is completely dissolved, then stopping stirring and lowering the system temperature to 0-35°C to obtain agarose gel; (2) mixing the nucleotide substance with the second portion of phosphate buffer, stirring to dissolve, and obtaining a nucleotide substance solution; (3) mixing lidocaine hydrochloride with the third portion of phosphate buffer, stirring to dissolve, and obtaining a lidocaine hydrochloride solution; (4) After the agarose gel is granulated through a sieve, it is mixed with a nucleotide solution and a lidocaine hydrochloride solution, and then degassed, filled, and irradiated for sterilization at a dose of 20 to 25 kGy to finally obtain a facial filler.

2. The method for preparing a facial filler according to claim 1, characterized in that: The nucleotide substances are polydeoxyribonucleotides or polynucleotides.

3. The method for preparing a facial filler according to claim 1, characterized in that: The pH of the phosphate buffer is 6.8-7.

3.

4. The method for preparing a facial filler according to claim 1, characterized in that: In the step (1), the mass ratio of agarose to the first part of phosphate buffer is 1:(12-60).

5. The method for preparing a facial filler according to claim 1, characterized in that: In the step (2), the mass ratio of the nucleotide substance to the second part of the phosphate buffer is 1:(20-150).

6. The method for preparing a facial filler according to claim 1, characterized in that: In the step (3), the mass ratio of lidocaine hydrochloride to the third part of phosphate buffer is 0.3:(3-18).

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