Racemic polylactic acid injection filler microsphere containing gamma-polyglutamic acid as well as preparation method and application of racemic polylactic acid injection filler microsphere

Abstract

The invention relates to a racemic polylactic acid injection filler microsphere containing gamma-polyglutamic acid as well as a preparation method and application of the racemic polylactic acid injection filler microsphere. The preparation method comprises the following steps: (1) injecting a racemic polylactic acid solution into a polyvinyl alcohol aqueous solution, homogenizing, and reacting at 30-40 DEG C for 4.5-5.5 hours to obtain PDLLA microspheres; (2) preparing a suspension from gamma-polyglutamic acid, sodium carboxymethyl cellulose and mannitol; and (3) adding the PDLLA microspheres into the suspension, uniformly mixing, and freeze-drying to obtain the gamma-polyglutamic acid-containing racemic polylactic acid injection filler microspheres. The prepared injection filler microspheres are high in yield, small in particle size, uniform in distribution, good in spherical appearance, free of adhesion, low in solvent residue and high in purity, nodules can be reduced to a great extent due to the fact that the particle size is not too large, and adverse reactions such as inflammation caused by phagocytosis of macrophages due to the fact that the particle size is too small are avoided; the compound is more suitable for being injected into a human body as a filler.

Description

Technical Field

[0001] The invention relates to racemic polylactic acid injection filler microspheres containing gamma-polyglutamic acid and a preparation method and application thereof, belonging to the technical field of medical cosmetic materials. Background Art

[0002] Injectable fillers (also known as skin fillers and soft tissue fillers) are mainly used to treat congenital defects and acquired defects. In recent years, they have been widely used in the field of medical cosmetology, such as filling and repairing skin wrinkles and depressions. Ideal injectable fillers have the following characteristics: ① safe, less damaging, good biocompatibility, not easy to be infected or induce foreign body granulomas; ② good stability, not easy to move, and can maintain a fixed volume and flexibility; ③ will not be swallowed by phagocytes; ④ effectively promote collagen regeneration, naturally and continuously change facial contours, and enhance the elasticity and moisture of the filled skin. Biodegradable injectable fillers include collagen, hyaluronic acid, calcium hydroxyapatite, polylactic acid, polycaprolactone, cross-linked hyaluronic acid, etc.

[0003] Polylactic acid is a completely degradable polymer material. It is polymerized by chemical synthesis using lactic acid, a product of microbial fermentation, as a monomer. According to the difference in the direction of rotation of the polarizer, polylactic acid can be divided into left-handed polylactic acid (PLLA), right-handed polylactic acid (PDLA), racemic polylactic acid (PDLLA), and non-optically active polylactic acid (Meso-PLLA), etc. Among them, polylactic acid containing the same proportion of monomers D-lactic acid and L-lactic acid is called racemic polylactic acid (PDLLA) because the rotation of polarized light cancels each other. Among them, PLLA should be more widely used in the field of cosmetic injections, and it has its own unique features as a cosmetic injection material.

[0004] However, the particle size distribution of PLLA microspheres prepared by the traditional method is wide, and the size is large and difficult to control. The wide particle size distribution will affect the efficiency of cell phagocytosis, reduce the targeting of the particles, and easily cause adverse reactions such as needle blocking and bulging. The current polylactic acid injection also has the problem of short degradation time. For example, Chinese patent document CN104258470A discloses a mixed gel of polylactic acid microspheres and cross-linked hyaluronic acid for injection and a preparation method thereof. The method is composed of polylactic acid microspheres and cross-linked hyaluronic acid gel. The polylactic acid microspheres have a molecular weight of 15000-120000, an average particle size of 10-150 μm, and a mass fraction of 5 to 25% in the mixed gel. The PLLA microparticles in this patented product are easily degraded in an aqueous environment, causing the microspheres to decompose or collapse, and are easy to aggregate. The microspheres are unevenly dispersed in the gel and injected into the skin, which is easy to form inflammatory reactions such as nodules, and have the disadvantages of poor stability, easy nodules, and short shelf life. Summary of the invention

[0005] In view of the deficiencies in the prior art, the present invention provides a racemic polylactic acid injection filler microsphere containing γ-polyglutamic acid and a preparation method and application thereof.

[0006] The technical solution of the present invention is as follows:

[0007] A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid comprises the following steps:

[0008] (1) adding racemic polylactic acid to dichloromethane to dissolve and mix well to obtain a racemic polylactic acid solution; then injecting the racemic polylactic acid solution into a polyvinyl alcohol aqueous solution, homogenizing for 1.5 to 2.5 minutes, and then reacting at 30 to 40° C. for 4.5 to 5.5 hours, centrifuging, precipitating, washing, and vacuum drying to obtain PDLLA microspheres;

[0009] (2) adding γ-polyglutamic acid, sodium carboxymethyl cellulose and mannitol to purified water in sequence, dissolving them, mixing them evenly, and adjusting the pH to 6.0 to 7.5 to obtain a suspension;

[0010] (3) adding the PDLLA microspheres obtained in step (1) to the suspension obtained in step (2), mixing evenly, and freeze-drying to obtain racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid.

[0011] Preferably according to the present invention, in step (1), the mass volume ratio of the racemic polylactic acid to dichloromethane is 1:(10-15), unit: g / mL.

[0012] Preferably according to the present invention, in step (1), the volume ratio of the racemic polylactic acid solution to the polyvinyl alcohol aqueous solution is 1:(8-12).

[0013] Preferably according to the present invention, in step (1), the mass concentration of the polyvinyl alcohol aqueous solution is 0.5-1.5%.

[0014] Preferably, according to the present invention, in step (1), the injection process is carried out while homogenizing, the injection speed is 10-20 mL / min, and the homogenization speed is 3000-4000 rpm.

[0015] Preferably according to the present invention, in step (2), the mass ratio of γ-polyglutamic acid, sodium carboxymethyl cellulose and mannitol is (1-2): (2.5-3.5): (6-8).

[0016] Preferably according to the present invention, in step (2), the mass volume ratio of the γ-polyglutamic acid and purified water is (0.05-0.07):5, unit: g / mL.

[0017] Preferably according to the present invention, in step (2), the pH is adjusted to 6.0-7.5 by using 2% phosphate buffer.

[0018] Preferably according to the present invention, in step (3), the mass volume ratio of the PDLLA microspheres to the suspension is 1:(20-30), unit: g / mL.

[0019] A racemic polylactic acid injection filler microsphere containing gamma-polyglutamic acid is prepared according to the method.

[0020] Preferably according to the present invention, the average particle size of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid is 8-80 μm, the mass fraction of racemic polylactic acid is 35-50%, and the mass fraction of γ-polyglutamic acid is 10-20%.

[0021] The application of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid in the preparation of soft tissue injection fillers.

[0022] Technical features and beneficial effects of the present invention:

[0023] 1. The present invention uses γ-polyglutamic acid and racemic polylactic acid as main filling components, sodium carboxymethyl cellulose and mannitol as auxiliary components, first prepares PDLLA microspheres by homogenization while injecting, then uses γ-polyglutamic acid, sodium carboxymethyl cellulose and mannitol to prepare suspension, and finally mixes and freeze-dries the two to prepare racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid. In the preparation method, by controlling the speed of the homogenizer, the sample addition time, and the ratio of dichloromethane to polyvinyl alcohol solution, the prepared injection filler microspheres have a high yield, a small particle size and uniform distribution, a good spherical appearance, no adhesion, low solvent residue, and high purity. At the same time, the activity of PDLLA and γ-PGA is retained to a great extent through the freeze-drying process.

[0024] 2. The injectable filler microspheres prepared by the present invention are uniform and smooth in shape, and the particle size of the microspheres can be about 8 to 80 μm. The particle size is not too large, which can greatly reduce the formation of nodules, and the particle size is not too small to be phagocytosed by macrophages, causing inflammation and other adverse reactions. They are more suitable for injection into the human body as fillers.

[0025] 3. Since the filling effect of racemic polylactic acid after injection cannot be immediately apparent, when the injectable filler microspheres provided by the present invention are injected into the living body, the filling and beauty effects of γ-polyglutamic acid and sodium carboxymethylcellulose are first exhibited. When the degradation of γ-polyglutamic acid and sodium carboxymethylcellulose is completed, the PDLLA microspheres can take over. The lactic acid generated by degradation can stimulate the production of collagen and new tissues in the skin itself, thereby achieving the effect of continuous filling, improving depression, removing wrinkles and whitening the cheeks, nose and lips. At the same time, racemic polylactic acid has a porous sponge-like morphology, so racemic polylactic acid can also provide a growth scaffold for the formation of tissues. As the racemic polylactic acid microspheres degrade, they can still provide support, which can increase the duration of the filling effect and enable it to maintain the filling effect for a long time. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is an electron microscope photograph of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in Example 1.

[0027] Figure 2 This is an electron microscope photograph of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in Example 2.

[0028] Figure 3 This is an electron microscope photograph of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in Comparative Example 1.

[0029] Figure 4 This is an electron microscope photograph of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in Comparative Example 3. DETAILED DESCRIPTION

[0030] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0031] Example 1

[0032] A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid comprises the following steps:

[0033] (1) 4 g of racemic polylactic acid was added to 50 ml of dichloromethane for dissolution, and the mixture was stirred to obtain a racemic polylactic acid solution as the oil phase; 2.5 g of polyvinyl alcohol was dissolved in 500 ml of water, and the mixture was stirred in a water bath at 70° C. for dissolution, and the mixture was cooled to room temperature to obtain a polyvinyl alcohol aqueous solution with a mass concentration of 0.5%; the racemic polylactic acid solution was then injected into the polyvinyl alcohol aqueous solution, and homogenization was performed while the mixture was injected. The homogenization speed was 3500 rpm, and the injection time was 3.5 min. After the injection was completed, the mixture was homogenized for 2 min, and the mixture was transferred to a stirrer for stirring at 35° C. for reaction for 5 hours. After the reaction was completed, the mixture was centrifuged and precipitated for washing, and finally transferred to a vacuum drying oven for drying at 40° C. for 24 h to obtain PDLLA microspheres;

[0034] (2) 0.3 g of γ-polyglutamic acid, 0.15 g of sodium carboxymethyl cellulose and 0.7 g of mannitol were added to 25 ml of purified water to dissolve, mixed evenly, and the pH was adjusted to 7.0 with 2% phosphate buffer to obtain a suspension;

[0035] (3) Add 1 g of the PDLLA microspheres obtained in step (1) to 25 ml of the suspension obtained in step (2), mix well, and then dispense into 5 ml vials and transfer to a freeze dryer for freeze drying to obtain racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid.

[0036] The electron microscope photo of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in this example is as follows: Figure 1 shown.

[0037] Depend on Figure 1 It can be seen that the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid in this embodiment were successfully prepared, and the microspheres were spherical as a whole, with relatively uniform particle sizes and no adhesion.

[0038] It has been determined that in the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid in this embodiment, the mass fraction of racemic polylactic acid accounts for 47%, and the mass fraction of γ-polyglutamic acid accounts for 14%.

[0039] Example 2

[0040] A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid comprises the following steps:

[0041] (1) Add 5 g of racemic polylactic acid to 50 ml of dichloromethane and dissolve it, stir and mix it evenly to obtain a racemic polylactic acid solution as the oil phase; take 2.5 g of polyvinyl alcohol and dissolve it in 500 ml of water, stir and dissolve it in a 70°C water bath, cool it to room temperature, and obtain a polyvinyl alcohol aqueous solution with a mass concentration of 0.5%; then inject the racemic polylactic acid solution into the polyvinyl alcohol aqueous solution, homogenize it while injecting, the homogenization speed is 4000 rpm, the injection time is 3.5 min, and after the injection is completed, continue to homogenize for 2 min, transfer it to a stirrer, stir and react at 30°C for 5.5 hours, centrifuge and wash the precipitate after the reaction is completed, and finally transfer it to a vacuum drying oven and dry it at 40°C for 24 hours to obtain PDLLA microspheres;

[0042] (2) 0.3 g of γ-polyglutamic acid, 0.15 g of sodium carboxymethyl cellulose and 0.7 g of mannitol were added to 25 ml of purified water to dissolve, mixed evenly, and the pH was adjusted to 7.0 with 2% phosphate buffer to obtain a suspension;

[0043] (3) Add 1 g of the PDLLA microspheres obtained in step (1) to 25 ml of the suspension obtained in step (2), mix well, and then dispense into 5 ml vials and transfer to a freeze dryer for freeze drying to obtain racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid.

[0044] The electron microscope photo of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in this example is as follows: Figure 2 shown.

[0045] Depend on Figure 2 It can be seen that the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid in this embodiment were successfully prepared and were spherical in shape as a whole.

[0046] It has been determined that in the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid in this embodiment, the mass fraction of racemic polylactic acid accounts for 46%, and the mass fraction of γ-polyglutamic acid accounts for 14%.

[0047] Example 3

[0048] A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid comprises the following steps:

[0049] (1) 4 g of racemic polylactic acid was added to 50 ml of dichloromethane for dissolution, and the mixture was stirred to obtain a racemic polylactic acid solution as the oil phase; 5 g of polyvinyl alcohol was dissolved in 500 ml of water, and the mixture was stirred in a water bath at 70° C. for dissolution, and the mixture was cooled to room temperature to obtain a polyvinyl alcohol aqueous solution with a mass concentration of 1%; the racemic polylactic acid solution was then injected into the polyvinyl alcohol aqueous solution, and homogenization was performed while the mixture was injected. The homogenization speed was 3500 rpm, and the injection time was 3.5 min. After the injection was completed, the mixture was homogenized for 2 min, and the mixture was transferred to a stirrer for stirring and reacting at 35° C. for 5 hours. After the reaction was completed, the mixture was centrifuged and precipitated for washing, and finally transferred to a vacuum drying oven for drying at 40° C. for 24 h to obtain PDLLA microspheres;

[0050] (2) 0.3 g of γ-polyglutamic acid, 0.15 g of sodium carboxymethyl cellulose and 0.7 g of mannitol were added to 25 ml of purified water to dissolve, mixed evenly, and the pH was adjusted to 7.0 with 2% phosphate buffer to obtain a suspension;

[0051] (3) Add 1 g of the PDLLA microspheres obtained in step (1) to 25 ml of the suspension obtained in step (2), mix well, and then dispense into 5 ml vials and transfer to a freeze dryer for freeze drying to obtain racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid.

[0052] Example 4

[0053] A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid comprises the following steps:

[0054] (1) Add 5 g of racemic polylactic acid to 50 ml of dichloromethane and dissolve it, stir and mix it evenly to obtain a racemic polylactic acid solution as the oil phase; take 2.5 g of polyvinyl alcohol and dissolve it in 500 ml of water, stir and dissolve it in a 70°C water bath, cool it to room temperature, and obtain a polyvinyl alcohol aqueous solution with a mass concentration of 0.5%; then inject the racemic polylactic acid solution into the polyvinyl alcohol aqueous solution, homogenize it while injecting, the homogenization speed is 3000 rpm, the injection time is 4 minutes, and after the injection is completed, continue to homogenize for 2 minutes, transfer it to a stirrer, stir and react at 40°C for 4.5 hours, centrifuge and wash the precipitate after the reaction is completed, and finally transfer it to a vacuum drying oven and dry it at 40°C for 24 hours to obtain PDLLA microspheres;

[0055] (2) 0.3 g of γ-polyglutamic acid, 0.15 g of sodium carboxymethyl cellulose and 0.7 g of mannitol were added to 25 ml of purified water to dissolve, mixed evenly, and the pH was adjusted to 7.0 with 2% phosphate buffer to obtain a suspension;

[0056] (3) Add 1 g of the PDLLA microspheres obtained in step (1) to 25 ml of the suspension obtained in step (2), mix well, and then dispense into 5 ml vials and transfer to a freeze dryer for freeze drying to obtain racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid.

[0057] Comparative Example 1

[0058] A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid, the specific steps are the same as those of Example 2, except that step (1) is: adding 5g of racemic polylactic acid to 50ml of dichloromethane to dissolve, stirring and mixing to obtain a racemic polylactic acid solution as an oil phase; taking 2.5g of polyvinyl alcohol and dissolving it in 500ml of water, stirring and dissolving it in a 70°C water bath, cooling it to room temperature, and obtaining a polyvinyl alcohol aqueous solution with a mass concentration of 0.5%; then injecting the racemic polylactic acid solution into the polyvinyl alcohol aqueous solution, injecting only the inhomogeneous, the injection time is 3.5min, then transferring it to a stirrer, stirring and reacting at 30°C for 5.5 hours, centrifuging and precipitating it after the reaction is completed, washing it, and finally transferring it to a vacuum drying oven and drying it at 40°C for 24h to obtain PDLLA microspheres.

[0059] The electron microscope photo of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in this comparative example is as follows: Figure 3 shown.

[0060] Depend on Figure 3 It can be seen that the injection filler microspheres prepared in this comparative example have irregular shapes, large particle sizes, and adhesion.

[0061] Comparative Example 2

[0062] A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid, the specific steps are the same as those of Example 2, except that step (1) is: adding 5g of racemic polylactic acid to 50ml of dichloromethane for dissolution, stirring and mixing to obtain a racemic polylactic acid solution as an oil phase; taking 2.5g of polyvinyl alcohol and dissolving it in 500ml of water, stirring and dissolving it in a 70°C water bath, cooling it to room temperature, and obtaining a polyvinyl alcohol aqueous solution with a mass concentration of 0.5%; then injecting the racemic polylactic acid solution into the polyvinyl alcohol aqueous solution, homogenizing while injecting, the homogenizing speed is 500rpm, the injection time is 10min, and after the injection is completed, the homogenization is continued for 2min, and the mixture is transferred to a stirrer, stirred and reacted at 30°C for 5.5 hours, centrifuged and precipitated after the reaction is completed, washed, and finally transferred to a vacuum drying oven and dried at 40°C for 24h to obtain PDLLA microspheres.

[0063] Comparative Example 3

[0064] A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid, the specific steps are the same as those of Example 2, except that step (1) is as follows: 5 g of racemic polylactic acid is added to 50 ml of dichloromethane for dissolution, and stirred and mixed to obtain a racemic polylactic acid solution as an oil phase; 2.5 g of polyvinyl alcohol is dissolved in 100 ml of water, stirred and dissolved in a 70°C water bath, and cooled to room temperature to obtain a polyvinyl alcohol aqueous solution with a mass concentration of 2.5%; then the racemic polylactic acid solution is injected into the polyvinyl alcohol aqueous solution, homogenized while injecting, the homogenization speed is 4000 rpm, the injection time is 3.5 min, and the homogenization is continued for 2 min after the injection is completed, and the mixture is transferred to a stirrer, stirred and reacted at 30°C for 5.5 hours, and after the reaction is completed, the precipitate is centrifuged and washed, and finally transferred to a vacuum drying oven and dried at 40°C for 24 h to obtain PDLLA microspheres.

[0065] The electron microscope photo of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in this comparative example is as follows: Figure 4 shown.

[0066] Depend on Figure 4 It can be seen that although the injection filler prepared in this comparative example has a large number of small particles, they are basically all adhered to each other, which affects subsequent use.

[0067] Test example

[0068] 1. The particle size distribution of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in Examples 1 to 4 was measured using a Malvern laser particle size analyzer, and the results are shown in Table 1. The particle size distribution includes D10, D50 and D90.

[0069] Table 1

[0070] Group / particle size D10(μm) D50(μm) D90(μm) Example 1 9.80 32.8 56.6 Example 2 10.23 26.5 56.8 Example 3 8.62 35.8 63.6 Example 4 11.67 38.3 79.0 Comparative Example 1 23.5 48.9 98.6 Comparative Example 2 26.8 49.1 80.2 Comparative Example 3 4.52 17.5 30.1

[0071] As can be seen from Table 1, the average particle size of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid prepared in Examples 1 to 4 of the present invention is 8 to 80 μm. Since Comparative Example 1 was not homogenized during injection, and Comparative Example 2 had a slow homogenization speed and a long injection time, the injection filler microspheres were irregular in shape, with many large particles and adhesion. Comparative Example 3 used a polyvinyl alcohol aqueous solution with a mass concentration of 2.5%. Although there were many small particles, they were basically all adhered, affecting subsequent use. This shows that in the preparation method of the present invention, by controlling the speed of the homogenizer, the sample addition time, and the ratio of dichloromethane to polyvinyl alcohol solution, the prepared injection filler microspheres have a high yield, a small particle size and a uniform distribution, a good spherical appearance, no adhesion, low solvent residue, and high purity, while retaining the activity of PDLLA and γ-PGA to a great extent.

Claims

1. A method for preparing racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid, characterized in that: The steps include: (1) adding racemic polylactic acid to dichloromethane to dissolve and mix well to obtain a racemic polylactic acid solution; then injecting the racemic polylactic acid solution into a polyvinyl alcohol aqueous solution, homogenizing for 1.5 to 2.5 minutes, and then reacting at 30 to 40° C. for 4.5 to 5.5 hours, centrifuging, precipitating, washing, and vacuum drying to obtain PDLLA microspheres; (2) adding γ-polyglutamic acid, sodium carboxymethyl cellulose and mannitol to purified water in sequence, dissolving them, mixing them evenly, and adjusting the pH to 6.0 to 7.5 to obtain a suspension; (3) adding the PDLLA microspheres obtained in step (1) to the suspension obtained in step (2), mixing evenly, and freeze-drying to obtain racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid.

2. The preparation method according to claim 1, characterized in that In step (1), the mass volume ratio of the racemic polylactic acid to dichloromethane is 1:(10-15), unit: g / mL.

3. The preparation method according to claim 1, characterized in that: In step (1), the volume ratio of the racemic polylactic acid solution to the polyvinyl alcohol aqueous solution is 1:(8-12).

4. The preparation method according to claim 1, characterized in that: In step (1), the mass concentration of the polyvinyl alcohol aqueous solution is 0.5-1.5%; the injection process is homogenized while injecting, the injection speed is 10-20 mL / min, and the homogenization speed is 3000-4000 rpm.

5. The preparation method according to claim 1, characterized in that: In step (2), the mass ratio of γ-polyglutamic acid, sodium carboxymethyl cellulose and mannitol is (1-2): (2.5-3.5): (6-8).

6. The preparation method according to claim 1, characterized in that: In step (2), the mass volume ratio of the γ-polyglutamic acid and purified water is (0.05-0.07):5, unit: g / mL.

7. The preparation method according to claim 1, characterized in that: In step (3), the mass volume ratio of the PDLLA microspheres to the suspension is 1:(20-30), unit: g / mL.

8. A racemic polylactic acid injection filler microsphere containing γ-polyglutamic acid, characterized in that: It is prepared according to the method according to any one of claims 1 to 7.

9. The racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid according to claim 8, characterized in that: The average particle size of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid is 8-80 μm, the mass fraction of racemic polylactic acid accounts for 35-50%, and the mass fraction of γ-polyglutamic acid accounts for 10-20%.

10. Use of the racemic polylactic acid injection filler microspheres containing γ-polyglutamic acid as claimed in claim 8 in the preparation of soft tissue injection fillers.

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