Sodium carboxymethyl cellulose gel, application thereof and preparation containing sodium carboxymethyl cellulose gel

Abstract

The invention discloses sodium carboxymethyl cellulose gel, application thereof and a preparation containing the sodium carboxymethyl cellulose gel. The sodium carboxymethyl cellulose gel is prepared by dispersing sodium carboxymethyl cellulose in water and sterilizing; the mass percent of the used sodium carboxymethyl cellulose is 3.8%-6%, the viscosity is 5800-15000 mPa.s, and the substitution degree is 0.75-0.82. According to the application, the types of the sodium carboxymethyl cellulose gel are specifically screened, and the anti-sterilization sodium carboxymethyl cellulose gel is successfully prepared. The sterilized sodium carboxymethyl cellulose gel still has ideal viscoelasticity, and the polyester microspheres have good dispersion stability in the sodium carboxymethyl cellulose gel, so that the use safety is high, and the sodium carboxymethyl cellulose gel is not easy to shift after being injected.

Description

Technical Field

[0001] The present invention relates to the field of medical aesthetics, and in particular to a sodium carboxymethylcellulose gel, applications thereof, and preparations containing the same. Background Art

[0002] With aging and various external stimuli, the loss of collagen in the dermis accelerates, causing the skin to become loose and wrinkles to appear. Medical cosmetic fillers can be used to improve skin condition. Currently, polyester microsphere fillers have become a hot topic of research in the medical aesthetics field due to their multiple advantages. For example, polyester microspheres have high biocompatibility, provide tissue support, and can induce fibroblast proliferation and myofibroblast differentiation, promoting collagen synthesis, thereby compensating for skin aging caused by collagen loss. Polyester microspheres also remain in the body for a long time, reducing the number of injections and effectively alleviating the pain of patients seeking cosmetic surgery.

[0003] For polyester microsphere-filled formulations, sodium carboxymethylcellulose can be used as the gel matrix. However, studies have shown that sterilization of sodium carboxymethylcellulose gel, whether by irradiation or moist heat, can affect its viscoelasticity, thereby affecting the dispersion stability of the polyester microspheres within the gel matrix. This can lead to needle blockage during injection, increasing the injection force, making the injection more difficult for the physician and more painful for the patient. Alternatively, uncontrolled injection force can lead to excessive local injection volume, resulting in complications such as local nodules or granulomas.

[0004] Therefore, there is an urgent need in this field to develop a sodium carboxymethyl cellulose gel with ideal viscoelasticity to ensure that polyester microspheres are stably dispersed in the sodium carboxymethyl cellulose gel, improve the safety of the injectable filler, reduce injection pain, reduce complications, and ensure a more natural filling effect. Summary of the Invention

[0005] The technical problem to be solved by this application is to overcome the defects of the existing sterilized sodium carboxymethyl cellulose gel, such as poor viscoelasticity, resulting in poor dispersion stability of microspheres therein and low safety in use, and to provide a sodium carboxymethyl cellulose gel, its application and preparation containing the same. This application conducts a specific screening of the types of sodium carboxymethyl cellulose gel and successfully produces a sterilization-resistant sodium carboxymethyl cellulose gel. It ensures that the sterilized sodium carboxymethyl cellulose gel still has ideal viscoelastic properties, the polyester microspheres therein have good dispersion stability, high safety in use, and are not prone to displacement after injection.

[0006] This application solves the above technical problems through the following technical solutions.

[0007] The present application provides a sodium carboxymethyl cellulose gel, which is prepared by dispersing sodium carboxymethyl cellulose in water and sterilizing it; the mass percentage of the sodium carboxymethyl cellulose used is 3.8% to 6%, the viscosity is 5800 to 15000 mPa·s, and the degree of substitution is 0.75 to 0.82.

[0008] In some embodiments, the viscosity of the sodium carboxymethyl cellulose is preferably 5800-12500 mPa·s, more preferably 6000-12000 mPa·s, and even more preferably 8000-12000 mPa·s, for example 6000 mPa·s, 7000 mPa·s, 8000 mPa·s, 9000 mPa·s, 10000 mPa·s, 11000 mPa·s, 12000 mPa·s, 13000 mPa·s, 14000 mPa·s, or 15000 mPa·s. The viscosity is the viscosity of a 2% by mass sodium carboxymethyl cellulose gel prepared by mixing sodium carboxymethyl cellulose and water using a rotational viscometer according to the European Pharmacopoeia method.

[0009] In some embodiments, the degree of substitution of the sodium carboxymethyl cellulose is preferably 0.75-0.8, such as 0.78 or 0.79.

[0010] In some embodiments, the sterilization method is moist heat sterilization.

[0011] In a preferred embodiment, the moist heat sterilization is performed under anaerobic conditions, more preferably under an inert atmosphere. The inert atmosphere is selected from an inert gas and / or nitrogen. The inert gas is selected from at least one of helium, neon, and argon.

[0012] In a preferred embodiment, the moist heat sterilization time is 10 to 40 minutes, preferably 15 to 30 minutes.

[0013] In a preferred embodiment, the temperature of the moist heat sterilization is 100-130°C, for example 121°C.

[0014] In some embodiments, the mass percentage of sodium carboxymethyl cellulose in the sodium carboxymethyl cellulose gel is preferably 4% to 5.5%, for example 4.5%.

[0015] In some embodiments, the sodium carboxymethylcellulose gel further comprises at least one of a lubricant, a buffer, and an anesthetic.

[0016] The lubricating moisturizer is selected from at least one of a polyol lubricating moisturizer, a carbohydrate lubricating moisturizer, and a polymer lubricating moisturizer. Preferably, the polyol lubricating moisturizer is selected from at least one of glycerol, propylene glycol, and sorbitol. Preferably, the carbohydrate lubricating moisturizer is selected from at least one of sodium hyaluronate, trehalose, and mannitol. The polymer lubricating moisturizer is polyethylene glycol.

[0017] The buffer is a buffer acceptable in the medical aesthetics field for regulating the pH and osmotic pressure of the system, preferably a phosphate buffer, more preferably a mixture of dihydrogen phosphate and dihydrogen phosphate. Preferably, the dihydrogen phosphate is selected from disodium hydrogen phosphate and / or dipotassium hydrogen phosphate. Preferably, the dihydrogen phosphate is selected from sodium dihydrogen phosphate and / or potassium dihydrogen phosphate.

[0018] Wherein, the anesthetic is selected from at least one of lidocaine hydrochloride, lidocaine carbonate, tetracaine, prilocaine, procaine, mepivacaine and bupivacaine.

[0019] The mass percentage of the lubricating moisturizer to the sodium carboxymethyl cellulose gel is 0.5% to 3%, preferably 0.5% to 1.5%, such as 0.8%, 1% or 1.2%.

[0020] Wherein, the mass percentage of the anesthetic to the sodium carboxymethyl cellulose gel is 0.1% to 0.6%.

[0021] The amount of the buffer used can be conventional in the art, and is generally used to adjust the pH value of the injectable filler to 6-8, and / or adjust the osmotic pressure of the injectable filler to isotonic.

[0022] In some embodiments, the elastic modulus G' of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 190 to 800 Pa, preferably 200 to 600 Pa, and more preferably 200 to 500 Pa, for example, 205 Pa, 250 Pa, 300 Pa, 350 Pa, 400 Pa, 450 Pa, 500 Pa, 550 Pa, 600 Pa, 650 Pa, 700 Pa, 750 Pa or 800 Pa.

[0023] In some embodiments, the viscous modulus G'' of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 170 to 500 Pa, preferably 170 to 400 Pa, and more preferably 170 to 350 Pa, for example, 180 Pa, 200 Pa, 250 Pa, 300 Pa, 320 Pa, 350 Pa, 400 Pa, 450 Pa or 500 Pa.

[0024] In some embodiments, the ratio G` / G`` of the elastic modulus G` and the viscous modulus G`` of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 1.1 to 2.5, preferably 1.1 to 2, for example, 1.14, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4 or 2.5.

[0025] In some embodiments, the sodium carboxymethyl cellulose gel is -1 The shear viscosity η at the shear rate is 160 to 650 Pa·s, preferably 170 to 550 Pa·s, for example, 170 Pa·s, 200 Pa·s, 250 Pa·s, 300 Pa·s, 350 Pa·s, 400 Pa·s, 450 Pa·s, 500 Pa·s, 550 Pa·s, 600 Pa·s or 650 Pa·s.

[0026] The present application also provides a use of the sodium carboxymethylcellulose gel as described above as a gel matrix in the preparation of an injectable filling material.

[0027] The present application also provides an injectable filler, which comprises polyester microspheres and the sodium carboxymethylcellulose gel as described above.

[0028] In some embodiments, the content of the polyester microspheres in the injectable filler is 200-400 mg / g, preferably 300-350 mg / g, for example 330 mg / g.

[0029] In some embodiments, the material of the polyester microspheres is selected from polycaprolactone.

[0030] In some embodiments, the weight average molecular weight of the polyester microsphere material is 10,000-40,000, preferably 10,000-25,000.

[0031] In some embodiments, the polyester microspheres have a particle size of 20-50 μm accounting for more than 80%, preferably more than 90%.

[0032] In some embodiments, the particle size D50 of the polyester microspheres is 20-50 μm, preferably 25-45 μm.

[0033] In some embodiments, the elastic modulus G' of the injectable filler at a frequency of 1 Hz is 800-3500 Pa, preferably 900-3100 Pa, for example 800 Pa, 1000 Pa, 1500 Pa, 2000 Pa, 2500 Pa, 3000 Pa or 3500 Pa.

[0034] In some embodiments, the viscous modulus G`` of the injectable filler at a frequency of 1 Hz is 550 to 2500 Pa, preferably 600 to 2000 Pa, and more preferably 600 to 1800 Pa, for example, 550 Pa, 600 Pa, 800 Pa, 1000 Pa, 1200 Pa, 1400 Pa, 1600 Pa, 1800 Pa, 2000 Pa, 2200 Pa, 2400 Pa or 2500 Pa.

[0035] In some embodiments, the injectable filler has a G` / G`` ratio of 1.2 to 2.5 at a frequency of 1 Hz, preferably 1.2 to 2, such as 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4 or 2.5.

[0036] In some embodiments, the method for preparing the polyester microspheres comprises the following steps: assembling the polyester microsphere materials described above into microspheres by an emulsified solvent volatilization method, and sterilizing the microspheres.

[0037] In a preferred embodiment, the method for preparing the polyester microspheres comprises the following steps: an organic phase comprises the material of the polyester microspheres and an organic solvent; an aqueous phase comprises a surfactant and water; and the organic phase and the aqueous phase are mixed, emulsified, solidified, and sterilized to obtain the polyester microspheres.

[0038] The organic solvent is selected from a halogenated alkane solvent and / or an ester solvent. Preferably, the halogenated alkane solvent is a chlorinated alkane solvent, more preferably selected from dichloromethane and / or chloroform. Preferably, the ester solvent is a C2-C6 alkyl acetate, more preferably ethyl acetate.

[0039] The mass volume ratio of the polyester microsphere material to the organic solvent is 80-450 g / L, preferably 100-300 g / L.

[0040] The volume ratio of the organic phase to the aqueous phase is 1:(3-20), preferably 1:(5-15), for example 1:10.

[0041] Wherein, the surfactant is polyvinyl alcohol, preferably polyvinyl alcohol 1788.

[0042] The mass volume ratio of the surfactant to the water is 8 to 50 g / L, preferably 15 to 40 g / L.

[0043] The viscosity of the water phase is 2-10 mPa·s and is measured at 25° C. using a rotational viscometer.

[0044] Wherein, the water is purified water.

[0045] The method for preparing the aqueous phase comprises the following steps: mixing the surfactant and the water at a mixing temperature of 60 to 120°C.

[0046] Wherein, the emulsification method includes mechanical stirring emulsification method, membrane emulsification method or homogeneous emulsification method.

[0047] The curing method includes a reduced pressure volatilization method and / or an air blowing method. According to conventional techniques in the art, the purpose of the curing is to remove the organic solvent in the system and promote the curing of the emulsion into microspheres.

[0048] The curing step may further include any one of collecting, drying, and screening. Preferably, the drying method is vacuum drying, which is commonly used in the art. More preferably, the drying temperature is 25 to 45°C. More preferably, the drying time is 12 to 48 hours.

[0049] Wherein, the sterilization method is selected from irradiation sterilization or moist heat sterilization.

[0050] On the basis of conforming to the common sense in this field, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present application.

[0051] The reagents and raw materials used in this application are commercially available.

[0052] The positive progress of this application lies in: through specific screening of sodium carboxymethylcellulose gel types, the application successfully produces a sterilization-resistant sodium carboxymethylcellulose gel. This ensures that the sterilized sodium carboxymethylcellulose gel still has ideal viscoelastic properties, and the polyester microspheres have good dispersion stability within it, making it highly safe to use and less prone to displacement after injection. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 The rheological diagram of sodium carboxymethyl cellulose gel prepared in Example 1;

[0054] Figure 2 The rheological diagram of sodium carboxymethyl cellulose gel prepared in Example 2;

[0055] Figure 3 The rheological diagram of the sodium carboxymethyl cellulose gel prepared in Example 3;

[0056] Figure 4 The rheological diagram of sodium carboxymethyl cellulose gel prepared in Comparative Example 1;

[0057] Figure 5 This is a diagram of the injectable filler prepared from the sodium carboxymethylcellulose gel of Example 1 after centrifugation;

[0058] Figure 6This is a diagram of the injectable filler prepared from the sodium carboxymethylcellulose gel of Example 2 after centrifugation;

[0059] Figure 7 This is a diagram of the injectable filler prepared from the sodium carboxymethylcellulose gel of Example 3 after centrifugation;

[0060] Figure 8 This is a diagram of the state of the injectable filler prepared from sodium carboxymethylcellulose gel in Comparative Example 1 after centrifugation. DETAILED DESCRIPTION

[0061] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. In the following examples, the experimental methods without specific conditions are selected according to conventional methods and conditions or according to the product specifications.

[0062] (1) The reagents and raw materials used in the following examples are all commercially available, and the purity of the reagents used is injection grade.

[0063] (2) The preparation method of polycaprolactone microspheres in the following effect embodiment comprises the following steps:

[0064] ① Preparation of aqueous phase: Add an appropriate amount of purified water to a container, slowly add 20 g of polyvinyl alcohol 1788, stir until completely dissolved, and adjust the volume to 1 L to obtain an aqueous phase with a viscosity of 7.5 mPa·s;

[0065] ② Preparation of organic phase: Add an appropriate amount of dichloromethane to a container, weigh 20 g of polycaprolactone with a weight average molecular weight of 15,000, add it to the container, stir to completely dissolve it, and adjust the volume to 100 mL to obtain an organic phase;

[0066] ③ Membrane emulsification: slowly pour the above organic phase into the aqueous phase, and use a membrane emulsifier to quickly emulsify the mixed liquid with a membrane tube pore size of 40 μm to obtain an emulsion;

[0067] ④Solidification: Stir the emulsified emulsion and blow nitrogen to volatilize the dichloromethane until the dichloromethane is completely evaporated;

[0068] ⑤ Collection: After the dichloromethane is completely evaporated, the suspension is centrifuged to collect the solid components, which are then dried and sterilized by irradiation to obtain spherical or elliptical polycaprolactone microspheres. The proportion of microspheres with a particle size of 20 to 50 μm is 86.4%, and D50 is 33.3 μm.

[0069] The pH value of the phosphate solution in the following examples and comparative examples is 7.

[0070] Preparation of sodium carboxymethylcellulose gel in Examples 1 to 3 and Comparative Example 1

[0071] Mix 94.5 g of phosphate solution (pH 7), 4.5 g of sodium carboxymethyl cellulose and 1 g of glycerol to prepare sodium carboxymethyl cellulose gel. Place the gel in a suitable sealed container and sterilize it by wet heat at 121° C. for 15 min under nitrogen gas to prepare sodium carboxymethyl cellulose gel.

[0072] The differences between the above examples and comparative examples are shown in Table 1 below.

[0073] Table 1

[0074] Viscosity of sodium carboxymethyl cellulose mPa·s Degree of substitution of sodium carboxymethyl cellulose Example 1 6000 0.78 Example 2 8000 0.78 Example 3 12000 0.79 Comparative Example 1 12000 0.85

[0075] Effect embodiment

[0076] The supporting performance of the sodium carboxymethyl cellulose gel for microspheres in the above examples and comparative examples was investigated, and the elastic modulus G', viscous modulus G'', elastic modulus to viscous modulus ratio G'' / G'', and shear viscosity η of the sodium carboxymethyl cellulose gel were tested. The results are shown in Table 2.

[0077] (1) Test method for elastic modulus G' and viscous modulus G': Dynamic frequency sweep was performed using a rheometer, with the test temperature set at 25°C, the frequency range at 0.1-10 Hz, the shear strain at 0.5%, and 10 sampling points per order of magnitude. The elastic modulus G' and viscous modulus G' at a frequency of 1 Hz were obtained. The results are shown in Table 2. The rheological diagrams of sodium carboxymethyl cellulose gels of Examples 1-3 and Comparative Example 1 are shown in Figures 1 to 4 ;

[0078] (2) Calculate the G` / G`` value. The results are shown in Table 2.

[0079] (3) Shear viscosity η test method: Use a rheometer to perform shear rate scanning, set the detection temperature to 25°C, and the shear rate range to 0.1s -1 ~100s -1 , set the gap to 0.3 mm, the scanning time to 3 min, the number of sampling points for each order of magnitude to 20, and the shear rate to 1 s -1 The shear viscosity values ​​under the conditions are shown in Table 2;

[0080] (4) Study on the supporting performance of microspheres: 100 g of the sodium carboxymethyl cellulose gel prepared above was mixed with 49 g of the polycaprolactone microspheres prepared by the above method under sterile conditions to prepare an injectable filler. About 1 g of the injectable filler was weighed and placed in a 1.5 mL centrifuge tube. The tube was centrifuged at 25°C and 20,000 rpm for 5 minutes. The product state was observed. The injectable fillers prepared with sodium carboxymethyl cellulose gels of Examples 1 to 3 and Comparative Example 1 showed the following product states after centrifugation: Figures 5 to 8 and Table 2.

[0081] Table 2

[0082]

[0083] According to the above results, the viscosity and degree of substitution of sodium carboxymethyl cellulose have a great influence on the viscoelasticity and properties of the prepared sodium carboxymethyl cellulose gel. The sodium carboxymethyl cellulose gel prepared in Example 1 is a gel-like viscous solution, which shows an ideal supporting effect on microspheres, and the configured injectable filler has no stratification after centrifugation. The sodium carboxymethyl cellulose gels prepared in Examples 2 to 3 are all gel-like products, and also have an ideal supporting effect on microspheres. However, the sodium carboxymethyl cellulose gel in Comparative Example 1 is a viscous solution. According to the stability results, it can be seen that its supporting effect on microspheres is poor, and the injectable filler configured with it is obviously stratified after centrifugation.

[0084] As shown in the above results, compared with the comparative example, the sodium carboxymethyl cellulose gel of the present application provides a more ideal support for the microspheres, ensuring that the injectable filler configured with it is less likely to cause needle blockage or complications during injection. It is highly safe to use, and its viscoelasticity meets the requirements of the field, resulting in a natural filling effect and a high aesthetic appearance after injection. The sodium carboxymethyl cellulose gel of the present application is a gel-like or gel-like product that exhibits more ideal cohesiveness and is less likely to shift after injection into tissue.

[0085] Finally, it should be noted that in this application, the terms "comprises", "includes" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or apparatus that includes a series of elements includes not only those elements, but also includes other elements not explicitly listed, or also includes elements that are inherent to such process, method, article or apparatus.

[0086] Although the present application has been disclosed above through the description of the specific embodiments of the present application, it should be understood that those skilled in the art may design various modifications, improvements or equivalents to the present application within the spirit and scope of the attached solutions. Such modifications, improvements or equivalents should also be considered to be included in the scope of protection claimed in the present application.

Claims

1. A sodium carboxymethylcellulose gel, characterized in that The sodium carboxymethyl cellulose gel is prepared by dispersing sodium carboxymethyl cellulose in water and sterilizing the water. The mass percentage of the sodium carboxymethyl cellulose used is 3.8% to 6%, the viscosity is 5800 to 15000 mPa·s, and the degree of substitution is 0.75 to 0.

82.

2. The sodium carboxymethylcellulose gel according to claim 1, wherein The sodium carboxymethyl cellulose gel satisfies at least one of the following conditions (1) to (9): (1) The viscosity of the sodium carboxymethyl cellulose is 5800 to 12500 mPa·s; (2) The degree of substitution of the sodium carboxymethyl cellulose is 0.75 to 0.8; (3) The sterilization method is moist heat sterilization; (4) The mass percentage of sodium carboxymethyl cellulose in the sodium carboxymethyl cellulose gel is 4% to 5.5%; (5) The sodium carboxymethylcellulose gel further comprises at least one of a lubricant, a buffer, and an anesthetic; (6) The elastic modulus G' of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 190 to 800 Pa; (7) The viscous modulus G'' of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 170 to 500 Pa; (8) The ratio G` / G`` of the elastic modulus G` to the viscous modulus G`` of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 1.1 to 2.5; (9) The sodium carboxymethyl cellulose gel is in 1s- 1 The shear viscosity η at the shear rate is 160 to 650 Pa·s.

3. The sodium carboxymethylcellulose gel according to claim 2, wherein The sodium carboxymethyl cellulose gel satisfies at least one of the following conditions (1) to (13): (1) The viscosity of the sodium carboxymethyl cellulose is 6000 to 12000 mPa·s; (2) The moist heat sterilization is carried out under anaerobic conditions; (3) The moist heat sterilization time is 10 to 40 minutes; (4) The temperature of the moist heat sterilization is 100-130°C; (5) The lubricating moisturizer is selected from at least one of a polyol lubricating moisturizer, a sugar lubricating moisturizer, and a polymer lubricating moisturizer; (6) The buffer is a phosphate buffer; (7) The anesthetic is at least one selected from the group consisting of lidocaine hydrochloride, lidocaine carbonate, tetracaine, prilocaine, procaine, mepivacaine, and bupivacaine; (8) The mass percentage of the lubricating moisturizer in the sodium carboxymethyl cellulose gel is 0.5% to 3%; (9) The mass percentage of the anesthetic in the sodium carboxymethyl cellulose gel is 0.1% to 0.6%; (10) The elastic modulus G' of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 200 to 600 Pa; (11) The viscous modulus G'' of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 170 to 400 Pa; (12) The ratio G` / G`` of the elastic modulus G` to the viscous modulus G`` of the sodium carboxymethyl cellulose gel at a frequency of 1 Hz is 1.1 to 2; (13) The sodium carboxymethyl cellulose gel is in 1s- 1 The shear viscosity η at the shear rate is 170 to 550 Pa·s.

4. The sodium carboxymethylcellulose gel according to claim 3, wherein The sodium carboxymethyl cellulose gel satisfies at least one of the following conditions (1) to (7): (1) The moist heat sterilization is carried out under an inert atmosphere; preferably, the inert atmosphere is selected from an inert gas and / or nitrogen; the inert gas is preferably selected from at least one of helium, neon and argon; (2) The moist heat sterilization time is 15 to 30 minutes; (3) the polyol lubricating and moisturizing agent is selected from at least one of glycerol, propylene glycol and sorbitol; (4) the carbohydrate lubricating and moisturizing agent is selected from at least one of sodium hyaluronate, trehalose and mannitol; (5) The polymer lubricating and moisturizing agent is polyethylene glycol; (6) The buffer is a mixture of dihydrogen phosphate and dihydrogen phosphate; (7) The mass percentage of the lubricating moisturizer in the sodium carboxymethyl cellulose gel is 0.5% to 1.5%.

5. Use of the sodium carboxymethylcellulose gel according to any one of claims 1 to 4 as a gel matrix in the preparation of an injectable filling material.

6. An injectable filler, characterized in that The invention comprises polyester microspheres and the sodium carboxymethyl cellulose gel according to any one of claims 1 to 4.

7. The injectable filler according to claim 6, wherein The injectable filler satisfies at least one of the following conditions (1) to (8): (1) The content of the polyester microspheres in the injectable filler is 200 to 400 mg / g; (2) The material of the polyester microspheres is polycaprolactone; (3) The weight average molecular weight of the polyester microsphere material is 10,000 to 40,000; (4) The polyester microspheres have a particle size of 20 to 50 μm and account for more than 80%; (5) The particle size D50 of the polyester microspheres is 20 to 50 μm; (6) The elastic modulus G′ of the injectable filler at a frequency of 1 Hz is 800 to 3500 Pa; (7) The injectable filler has a viscous modulus G′′ of 550 to 2500 Pa at a frequency of 1 Hz; (8) The preparation method of the polyester microspheres comprises the following steps: assembling the polyester microsphere materials into microspheres by an emulsified solvent volatilization method, and then sterilizing the microspheres.

8. The injectable filler according to claim 7, wherein The injectable filler satisfies at least one of the following conditions (1) to (7): (1) The content of the polyester microspheres in the injectable filler is 300-350 mg / g; (2) The weight average molecular weight of the polyester microsphere material is 10,000 to 25,000; (3) The polyester microspheres have a particle size of 20 to 50 μm and account for more than 90%; (4) The particle size D50 of the polyester microspheres is 25 to 45 μm; (5) The elastic modulus G′ of the injectable filler at a frequency of 1 Hz is 900 to 3100 Pa; (6) The injectable filler has a viscous modulus G′′ of 600 to 2000 Pa at a frequency of 1 Hz; (7) The preparation method of the polyester microspheres comprises the following steps: an organic phase comprises the material of the polyester microspheres and an organic solvent; an aqueous phase comprises a surfactant and water; the organic phase and the aqueous phase are mixed, emulsified, solidified, and sterilized.

9. The injectable filler according to claim 8, wherein The viscous modulus G'' of the injectable filler at a frequency of 1 Hz is 600 to 1800 Pa.

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