Injectable skin filler as well as preparation method and application thereof

Abstract

The invention relates to an injectable skin filler. The injectable skin filler comprises hydrophilic modified adhesive polyester microspheres, a suspending agent and a synergist, the mass ratio of the hydrophilic modified adhesive polyester microspheres to the suspending agent to the synergist is (1-5): 1: (0.1-2); the hydrophilic modified adhesive polyester microsphere is an amphiphilic polymer composite polyester microsphere, and the amphiphilic polymer is a catechol-terminated amphiphilic polymer. The invention further provides a preparation method of the injectable skin filling agent. Polyester microspheres are modified through the amphiphilic polymer terminated by catechol. The device can be widely applied to medical cosmetology.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to an injectable skin filler and a preparation method and application thereof. Background Art

[0002] In recent years, injectable skin fillers for cosmetic and medical purposes have developed rapidly. Injectable skin fillers can achieve the cosmetic effect of minimally invasive treatment at the injection site and have attracted widespread attention. The soft tissue fillers currently on the market mainly include cross-linked sodium hyaluronate gel, collagen, polycaprolactone, polylactic acid and hydroxyapatite. Among them, the action time of cross-linked sodium hyaluronate gel and collagen in the skin is 6 to 12 months, and the action time of polycaprolactone, polylactic acid and calcium hydroxyapatite in the skin is about 2 years or more. Polyester materials such as polylactic acid, polycaprolactone and its monomers have the advantages of good biocompatibility, non-toxicity and low immunity, so they are widely used in the fields of biomedicine and tissue engineering. At present, there are many products containing polylactic acid and / or polycaprolactone used for filling skin wrinkles and depressions, and their main forms are polylactic acid microparticles, polylactic acid microspheres and polycaprolactone microspheres. However, there are similar problems such as high preparation cost, slow reaction speed, complex structure and poor material performance.

[0003] For example, some powder-based baby face injections require a long time (usually about 24 hours) of hydration before they can be used for intradermal injection as cosmetic injection fillers, which brings inconvenience to patients. In addition, after hydration, the filler needs to be mixed before injection, which makes it difficult for the polylactic acid particles to be fully mixed and easily aggregated, resulting in the appearance of subcutaneous nodules.

[0004] The solution proposed in patents CN 104258470B, CN 109621003A, and CN 105879124 B is to prepare the filler directly into a gel form to avoid the re-dissolution problem. However, studies have found that polyester microspheres cannot exist stably for a long time in an aqueous environment. If stored for more than one month, problems such as microsphere structure collapse or microsphere adhesion may occur. In addition, gel products cannot be sterilized by irradiation. For low-melting-point polyester materials such as polycaprolactone, high-temperature wet heat sterilization is not suitable, resulting in a complicated product sterilization procedure and high production line costs.

[0005] The amphiphilic polyester microspheres mentioned in the prior art mainly refer to amphiphilic polylactic acid materials, but are not applicable to other polyester materials that are difficult to hydrophilically modify. In addition, the amphiphilic microspheres only improve their suspension and dispersion properties in gel solutions. After implantation in the body, they face the problem of microsphere migration and aggregation caused by the degradation of the suspension and dispersion medium, just like other polyester microspheres. Summary of the invention

[0006] The purpose of the present invention is to provide an injectable skin filler and a preparation method and application thereof, which solves the problem in the prior art that polyester microspheres are easy to agglomerate after reconstitution due to the strong hydrophobicity of polyester and are forced to migrate after entering the skin tissue.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is:

[0008] A first aspect of the present invention provides an injectable dermal filler comprising:

[0009] Hydrophilically modified adhesive polyester microspheres, suspending agents and synergists;

[0010] The mass ratio of the hydrophilically modified adhesive polyester microspheres, the suspending agent and the synergist is 1-5:1:0.1-2;

[0012] The hydrophilically modified adhesive polyester microspheres are amphiphilic polymer composite polyester microspheres, wherein the polyester microspheres are a mixture of one or more selected from the group consisting of left-handed polylactic acid microspheres, right-handed polylactic acid microspheres, racemic polylactic acid microspheres, polyglycolide microspheres, polycaprolactone microspheres, polydioxanone microspheres and polyester block copolymer microspheres;

[0013] The amphiphilic polymer is a catechol-terminated amphiphilic polymer.

[0014] Furthermore, the particle size of the polyester microspheres is 10-80 μm.

[0015] Furthermore, the suspending agent is a mixture of one or more selected from sodium carboxymethyl cellulose, sodium hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hyaluronic acid and its derivatives and collagen; and the synergist is mannitol.

[0016] Furthermore, the polyester block copolymer is a mixture of one or more selected from polyethylene glycol-polycaprolactone-polyethylene glycol, polyethylene glycol-polycaprolactone and polyethylene glycol-polylactic acid.

[0017] Furthermore, the mass ratio of the hydrophilically modified adhesive polyester microspheres, the suspending agent and the synergist is 3:1:1.

[0018] Further, the catechol-terminated amphiphilic polymer includes a catechol-terminated diblock copolymer and a catechol-terminated triblock copolymer;

[0019] The diblock copolymers include polyethylene glycol-polylactic acid, polyethylene glycol-polycaprolactone, polyethylene glycol-polybutylene oxide, polyethylene glycol-polyglycolic acid and acrylic acid-polylactic acid copolymers;

[0020] The triblock copolymers include polyethylene glycol-polylactic acid-polyethylene glycol, polyethylene glycol-polycaprolactone-polyethylene glycol, polyethylene glycol-polybutylene oxide-polyethylene glycol, polyethylene glycol-polyglycolic acid-polyethylene glycol, polyethylene glycol-poly(lactic acid-glycolic acid) and polyethylene glycol-polylactic acid-glycolic acid copolymers.

[0021] A second aspect of the present invention provides a method for preparing an injectable dermal filler, comprising the following steps:

[0022] (1) dissolving the polyester in an organic solvent to obtain an organic solution of the polyester;

[0023] (2) dissolving a dispersant in the poor solvent for the polyester in step (1) to obtain a dispersant solution;

[0024] (3) adding the polyester organic solution to the dispersant solution, stirring thoroughly and then allowing to settle to obtain polyester microspheres;

[0025] (4) dissolving the catechol-terminated amphiphilic polymer in a volatile solvent to prepare a modified solution;

[0026] (5) adding the polyester microspheres in step (3) into the modified solution, stirring and dispersing the solution, and filtering and drying the solution to obtain hydrophilically modified adhesive polyester microspheres;

[0027] (6) dissolving the suspending agent and the synergist in water, adding the hydrophilically modified adhesive polyester microspheres described in step (5) thereto and mixing evenly, and freeze-drying to obtain the injectable dermal filler.

[0028] Furthermore, in step (1), the organic solvent is a good solvent for the polyester, and the good solvent is a mixture of one or more selected from tetrahydrofuran, chloroform, ethyl acetate and dichloromethane;

[0029] In step (2), the dispersant is a mixture of one or more selected from polyvinyl pyrrolidone, polyethylene glycol, polyvinyl alcohol and polyacrylamide; the poor solvent for the polyester is selected from water and a mixture of water and methanol or ethanol.

[0030] Furthermore, in step (4), the mass concentration of the modified solution is 0.5% to 3%; the volatile solvent is dichloromethane or a mixture of dichloromethane and an alcohol solvent or chloroform or a mixture of chloroform and an alcohol solvent; the alcohol solvent is methanol, ethanol or isopropanol; the mixing ratio of the dichloromethane / chloroform to the alcohol solvent is (1 to 9):(1 to 9).

[0031] Furthermore, in step (6), the freeze-drying temperature is -40°C to -38°C, the freeze-drying time is 12 to 48 hours, and the vacuum degree is 0.5 to 1.0 Pa.

[0032] The third aspect of the present invention provides a use of an injectable dermal filler in medical cosmetology, wherein the injectable dermal filler is a lyophilized agent and is diluted with a phosphate buffer solution before injection.

[0033] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0034] The present invention covers the surface of the polyester microspheres with an amphiphilic polymer so that the microspheres can be quickly dispersed, quickly re-dissolved and have good stability, and have good biocompatibility and degradability. After being injected into human tissues, the modified microspheres have tissue adhesion and are fixed at the target position, which can effectively avoid adverse tissue reactions caused by the migration of the microspheres. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Hereinafter, some specific embodiments of the present invention will be described in detail in an exemplary and non-limiting manner with reference to the accompanying drawings. The same reference numerals in the accompanying drawings indicate the same or similar components or parts. It should be understood by those skilled in the art that these drawings are not necessarily drawn to scale. In the accompanying drawings:

[0036] Figure 1 This is a scanning electron microscope image of the injectable dermal filler prepared in Example 1 provided in the present invention;

[0037] Figure 2 This is a scanning electron microscope image of the injectable dermal filler prepared in Example 2 provided in the present invention;

[0038] Figure 3 This is a scanning electron microscope image of the injectable dermal filler prepared in Example 3 provided in the present invention;

[0039] Figure 4 This is a scanning electron microscope image of the injectable dermal filler prepared in Comparative Example 1 provided in the present invention;

[0040] Figure 5 This is a scanning electron microscope image of the injectable dermal filler prepared in Comparative Example 2 provided in the present invention;

[0041] Figure 6 This is a HE staining result of the tissue site 15 days after the injectable dermal filler prepared in Example 1 provided in the present invention was injected;

[0042] Figure 7 This is a HE staining result of the tissue site 15 days after the injectable dermal filler prepared in Example 2 provided in the present invention was injected;

[0043] Figure 8 This is a HE staining result of the tissue site 15 days after the injectable dermal filler prepared in Comparative Example 2 provided in the present invention was injected;

[0044] Fig. 9 This is a HE staining result of the tissue site one month after the injectable dermal filler prepared in Example 1 provided by the present invention was injected;

[0045] Fig.10 This is a HE staining result of the tissue site one month after the injectable dermal filler prepared in Example 2 provided by the present invention was injected;

[0046] Fig.11 This is a HE staining result of the tissue site one month after the injectable dermal filler prepared in Comparative Example 2 provided in the present invention was injected;

[0047] Fig.12 This is a HE staining result of the tissue site 90 days after the injectable dermal filler prepared in Example 1 provided in the present invention was injected;

[0048] Fig.13 This is a HE staining result of the tissue site 90 days after the injectable dermal filler prepared in Example 2 provided by the present invention was injected;

[0049] Fig.14 This is a HE staining result of the tissue site 90 days after the injectable dermal filler prepared in Comparative Example 2 provided in the present invention was injected;

[0050] Fig.15 This is a HE staining result of the tissue site one year after the injectable dermal filler prepared in Example 1 provided by the present invention was injected;

[0051] Fig.16 This is a HE staining result of the tissue site one year after the injectable dermal filler prepared in Example 2 provided by the present invention was injected;

[0052] Fig.17 This is a HE staining result of the tissue site one year after the injectable dermal filler prepared in Comparative Example 2 provided in the present invention was injected. DETAILED DESCRIPTION

[0053] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. 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 creative work are within the scope of protection of the present invention.

[0054] Embodiment 1:

[0055] This embodiment provides an injectable dermal filler and a preparation method thereof, comprising the following steps:

[0056] (1) Weigh 2±0.1 g of poly (L-lactic acid) (intrinsic adhesion (IV, dl / g): 0.90-1.20; purchased from Corbion) and 100±10 mL of dichloromethane (analytical grade, purchased from Sinopharm Chemical Reagent Co., Ltd.) into a blue-capped bottle and stir magnetically at 500 rpm for 4±1 h until completely dissolved;

[0057] (2) Weigh 5±0.5 g of polyvinyl alcohol (pharmaceutical excipient grade, purchased from Hunan Erkang Pharmaceutical Co., Ltd.) and 1000±100 mL of purified water (homemade) and place them in a 2 L glass beaker. Heat in an 80 °C water bath with mechanical stirring (300 rpm) for 2±0.5 h until completely dissolved, then remove from the water bath and cool to room temperature.

[0058] (3) While maintaining mechanical stirring at 300 rpm, the poly-L-lactic acid solution in step (1) was added to the continuously stirred polyvinyl alcohol aqueous solution using a peristaltic pump at a feeding speed of 10 to 30 rpm. After stirring at room temperature for 12 h, the supernatant solution was discarded, and the microspheres between the 300-mesh and 800-mesh sieves were taken and dried at room temperature to obtain poly-L-lactic acid microspheres;

[0059] (4) 0.2 g of catechol-terminated polyethylene glycol-polylactic acid (purchased from Beijing Jingpi Technology Co., Ltd.) was added to 10 mL of dichloromethane-methanol solution (dichloromethane: methanol = 5:5) to prepare a modified solution with a mass concentration of 2%, and stirred at room temperature until completely dissolved to prepare a modified solution;

[0060] (5) adding 5 g of the poly (L-lactic acid) microspheres prepared in step (3) to the modified solution, stirring to disperse the microspheres; then filtering to separate the microspheres from the solution, placing the microspheres in a forced air drying oven at room temperature until completely dried, thereby obtaining catechol-terminated polyethylene glycol-polylactic acid modified poly (L-lactic acid) microspheres;

[0061] (6) Dissolve 1 g of sodium carboxymethyl cellulose (molecular weight 30,000 DA) and 1 g of mannitol in 30 mL of pure water, heat at 80° C. until completely dissolved, add 3 g of polyethylene glycol-polylactic acid modified poly-L-lactic acid microspheres prepared in step (5) after cooling, mix well, fill into a vial, freeze-dry at -40° C. to -38° C., and sterilize by irradiation to obtain an injectable dermal filler.

[0062] Embodiment 2:

[0063] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the mass concentration of the modified solution in step (4) is 0.5%. Finally, an injectable dermal filler is also prepared.

[0064] Embodiment 3:

[0065] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the mass concentration of the modified solution in step (4) is 3%. Finally, an injectable dermal filler is also prepared.

[0066] Embodiment 4:

[0067] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the polyester used in step (1) is polyglycolide, and an injectable dermal filler is finally prepared.

[0068] Embodiment 5:

[0069] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the dispersant used in step (2) is polyvinyl pyrrolidone, and an injectable dermal filler is finally prepared.

[0070] Embodiment 6:

[0071] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the catechol-terminated amphiphilic polymer used in step (4) is polyethylene glycol-polycaprolactone, and an injectable dermal filler is finally prepared.

[0072] Embodiment 7:

[0073] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the catechol-terminated amphiphilic polymer used in step (4) is polyethylene glycol-polylactic acid-polyethylene glycol, and an injectable dermal filler is finally prepared.

[0074] Embodiment 8:

[0075] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the suspending agent used in step (6) is hyaluronic acid, which has a weight average molecular weight of 180-230w and dissolves at room temperature. Finally, an injectable dermal filler is prepared.

[0076] Embodiment 9:

[0077] This embodiment provides an injectable skin filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the feeding amounts of mannitol and polyethylene glycol-polylactic acid modified poly-L-lactic acid microspheres used in step (6) are 2 g and 5 g respectively, and finally an injectable skin filler is prepared.

[0078] Embodiment 10:

[0079] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the feeding amounts of mannitol and polyethylene glycol-polylactic acid modified poly-L-lactic acid microspheres used in step (6) are 0.1 g and 1 g, respectively, and finally an injectable dermal filler is prepared.

[0080] Comparative Example 1

[0081] This embodiment provides an injectable dermal filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the mass concentration of the modified solution in step (4) is 4%. Finally, an injectable dermal filler is also prepared.

[0082] Comparative Example 2

[0083] This embodiment provides an injectable skin filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the polyester microspheres are not modified with catechol-terminated amphiphilic polymers. Finally, an injectable skin filler is also prepared.

[0084] Comparative Example 3:

[0085] This embodiment provides an injectable skin filler and a preparation method thereof. The only difference between this embodiment and embodiment 1 is that the feeding amounts of mannitol and polyethylene glycol-polylactic acid modified poly-L-lactic acid microspheres used in step (6) are 3 g and 6 g, respectively. Finally, an injectable skin filler is also prepared.

[0086] In the present invention, the injectable dermal fillers prepared in the above-mentioned Examples 1 to 3 and Comparative Examples 1 to 2 were observed by scanning electron microscopy (SEM), and the results corresponded to Figure 1 , Figure 2 , Figure 3 , Figure 4 and Figure 5 .

[0087] Specifically, from Figure 5 It can be seen that the polyester microspheres were not modified with catechol-terminated amphiphilic polymers. The surface of the poly-L-lactic acid microspheres was smooth and dense but accompanied by a small number of pits with sharp edges. These pits were caused by phase separation during the evaporation of the solvent.

[0088] Figure 2 It shows that after modification with 0.5% catechol-terminated polyethylene glycol-polylactic acid, the pits on the surface of the microspheres became shallower and the surface was smoother, and the smoothness of the surface of the microspheres decreased, indicating that the surface of the microspheres was successfully modified with a layer of material.

[0089] As the concentration of the modified solution increases, the surface morphology of the microspheres also changes. After modification with a 2% concentration modified solution, the microspheres ( Figure 1 ) There are a few debris on the surface, which is due to the deposition of the modified substances, but the microspheres maintain a smooth surface and the pits are covered by the amphiphilic polymer.

[0090] As the concentration of the modified solution increases further, the surface morphology of the microspheres also changes further. Figure 3 The surface of the microspheres is rough but the microspheres remain dispersed; it can be seen from the figure that the higher the concentration of the modified solution, the more amphiphilic substances are coated on the surface of the polyester microspheres, causing regular changes in the surface morphology of the microspheres.

[0091] However, a large number of fragments were generated in the sample prepared in Comparative Example 1 ( Figure 4 ), which should be avoided when filling microspheres.

[0092] In addition, the present invention also conducted a re-dissolution experiment on the injectable dermal fillers prepared in Comparative Examples 1 to 3 of Examples 1 to 10 above, and the specific operation steps are as follows:

[0093] Take 0.3 g of the injection powder prepared in Examples 1 to 10 and Comparative Examples 1 to 3, dissolve it in 5 ml of physiological saline and shake it gently, and record the complete reconstitution state and time.

[0094] The complete re-dissolution time and the re-dissolution effect of 10 min for Examples 1 to 10 and Comparative Examples 1 to 3 are shown in the following table:

[0095]

[0096]

[0097]

[0098] From the time required for complete re-dissolution of Examples 1 to 10 and Examples 1 to 3, it can be seen that modifying the microspheres can effectively shorten the re-dissolution time of the injection, and the higher the concentration of the modified solvent, the shorter the time taken, but increasing the proportion of microspheres in the filler is not conducive to the rapid re-dissolution of the filler. Example 1, Example 3 and Comparative Example 1 can be completely re-dissolved in just 10 minutes, while Comparative Example 2 requires 30 minutes to be completely re-dissolved, and there are obvious floccules in the solution after 10 minutes of re-dissolution; the time for complete re-dissolution of Comparative Example 3 is 25 minutes, which is longer than that of Examples 1-10. The 10-minute re-dissolution effect is worse than that of Examples 1-10, but better than Comparative Example 2. From the re-dissolution time, it can be seen that the amphiphilic polymer coated on the surface of the polyester microspheres is conducive to the re-dissolution of the filler.

[0099] The present invention also conducted a filling effect experiment on the injectable skin fillers in Examples 1-2 and Comparative Example 2. Specifically, the injectable powders in Examples 1-2 and Comparative Example 2 were sterilized, added with 5 ml of physiological saline for reconstitution for 30 minutes, and then injected into the back of the experimental rabbit, with 0.2 ml injected. The injection site was regularly sampled for HE staining to observe the effect and inflammation condition.

[0100] The results of HE staining of tissue sites 15 days after injection were as follows Figures 6 to 8 As shown in the figure, it can be seen that the dispersibility of the microspheres prepared in Examples 1 and 2 is better than that in Comparative Example 2. The microspheres in Comparative Example 2 are severely agglomerated. Because the reconstituted samples before injection are evenly dispersed and the injection concentration and conditions are consistent, the reason for the agglomeration of the microspheres is the agglomeration caused by the movement and squeezing of the rabbits. Examples 1 to 2 avoid this displacement and agglomeration tendency due to the tissue adhesion of the microspheres.

[0101] The results of HE staining of tissues one month after injection were as follows: Figures 9-11 As shown, compared Figures 9-11 It can be seen that the microspheres prepared in Example 2 have a slight tendency to agglomerate 30 days after injection into the body. This is because of the movement of the animal and the degradation and shedding of the tissue adhesive material on the surface of the polyester microspheres, and because the time is short, the tissue has not yet completely fixed the microspheres. The content of tissue adhesive amphiphilic polymer covered on the surface of the microspheres used in Example 1 is higher than that used in Example 2, and its tissue adhesive effect is longer than that of Example 2, so the dispersion of the microspheres is still good.

[0102] The results of HE staining of tissues at three months after injection are as follows Figures 12-14 As shown, compared Figures 12-14 It can be seen that the microspheres prepared in Example 2 were slightly aggregated 90 days after injection into the body, and the inflammatory stimulation was relatively mild, which was consistent with the results 30 days after injection. The microspheres in Example 1 were still well dispersed, and the microspheres were completely fixed by the tissue at this time, while the microspheres in Comparative Example 2 were severely aggregated, and the aggregated microspheres were fixed by the tissue.

[0103] The results of HE staining of tissues one year after injection are as follows Figures 15 to 17 As shown, from Fig.16 It can be seen that the microspheres have good dispersion and no agglomeration, and the dispersion is better than Fig.15 , Fig.17 The microspheres in the sample had the most serious agglomeration.

[0104] Comparative Analysis Figures 6 to 17 It can be seen that the modified microspheres have greatly improved dispersibility when the filler is injected into the body. Because the microspheres have tissue adhesion, the microspheres are well fixed at the injection site after entering the body, thereby avoiding the agglomeration of microspheres caused by the degradation of the suspending agent and the continuous movement and extrusion of the animal. As time goes by, the adhesive substances on the surface of the microspheres degrade and the microspheres coated with tissues can still maintain good dispersibility. From the comparative test results of Example 1 and Example 2, it can be seen that the more the teaphenol-terminated polyethylene glycol-polylactic acid is covered, the longer the microsphere adhesion is maintained.

[0105] from Figure 6 , 9 The results of 12 and 15 show that the microspheres used in the filler prepared in Example 1 have an appropriate content of the surface-modified copolymer. After being injected into the body, the microspheres remain dispersed due to their own adhesion. After the copolymer on the surface is slowly degraded, it remains dispersed due to the coating of the tissue, thereby avoiding adverse reactions caused by microsphere agglomeration.

[0106] In summary, the injectable skin filler of hydrophilically modified adhesive polyester microspheres provided by the present invention can immediately fill subcutaneous tissue and smooth wrinkles under the action of the synergist gel after dilution and injection. Subsequently, the adhesive copolymer on the surface of the microspheres reacts with the human tissue for fixation, thereby preventing the polyester microspheres from moving and agglomerating due to the loss of the plasticizer. As time goes by, the adhesive copolymer slowly degrades, but the polyester microspheres are also coated and fixed by the human tissue; the gradual degradation of the polyester microspheres can stimulate the subcutaneous immune response, so that the body produces collagen, and continues to fill and maintain the subcutaneous capacity.

[0107] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with this technology to understand the contents of the present invention and implement them accordingly. They cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. An injectable dermal filler, characterized in that: include: Hydrophilically modified adhesive polyester microspheres, suspending agents and synergists; The mass ratio of the hydrophilically modified adhesive polyester microspheres, the suspending agent and the synergist is 1-5:1:0.1-2; The hydrophilically modified adhesive polyester microspheres are amphiphilic polymer composite polyester microspheres, wherein the polyester microspheres are a mixture of one or more selected from the group consisting of left-handed polylactic acid microspheres, right-handed polylactic acid microspheres, racemic polylactic acid microspheres, polyglycolide microspheres, polycaprolactone microspheres, polydioxanone microspheres and polyester block copolymer microspheres; The amphiphilic polymer is a catechol-terminated amphiphilic polymer.

2. The injectable dermal filler according to claim 1, characterized in that: The particle size of the polyester microspheres is 10-80 μm.

3. The injectable dermal filler according to claim 1, characterized in that: The suspending agent is a mixture of one or more selected from sodium carboxymethylcellulose, sodium hydroxyethylcellulose, hydroxypropylmethylcellulose, hyaluronic acid and its derivatives and collagen; the synergist is mannitol.

4. The injectable dermal filler according to claim 1, characterized in that: The polyester block copolymer is a mixture of one or more selected from polyethylene glycol-polycaprolactone-polyethylene glycol, polyethylene glycol-polycaprolactone and polyethylene glycol-polylactic acid.

5. The injectable dermal filler according to claim 1, characterized in that: The catechol-terminated amphiphilic polymer includes a catechol-terminated diblock copolymer and a catechol-terminated triblock copolymer; The diblock copolymers include polyethylene glycol-polylactic acid, polyethylene glycol-polycaprolactone, polyethylene glycol-polybutylene oxide, polyethylene glycol-polyglycolic acid and acrylic acid-polylactic acid copolymers; The triblock copolymers include polyethylene glycol-polylactic acid-polyethylene glycol, polyethylene glycol-polycaprolactone-polyethylene glycol, polyethylene glycol-polybutylene oxide-polyethylene glycol, polyethylene glycol-polyglycolic acid-polyethylene glycol, polyethylene glycol-poly(lactic acid-glycolic acid) and polyethylene glycol-polylactic acid-glycolic acid copolymers.

6. A method for preparing an injectable dermal filler according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) dissolving the polyester in an organic solvent to obtain an organic solution of the polyester; (2) dissolving a dispersant in the poor solvent for the polyester in step (1) to obtain a dispersant solution; (3) adding the polyester organic solution to the dispersant solution, stirring thoroughly and then allowing to settle to obtain polyester microspheres; (4) dissolving the catechol-terminated amphiphilic polymer in a volatile solvent to prepare a modified solution; (5) adding the polyester microspheres in step (3) into the modified solution, stirring and dispersing the solution, and filtering and drying the solution to obtain hydrophilically modified adhesive polyester microspheres; (6) dissolving the suspending agent and the synergist in water, adding the hydrophilically modified adhesive polyester microspheres described in step (5) thereto and mixing them evenly, and freeze-drying to obtain the injectable dermal filler.

7. The method for preparing an injectable dermal filler according to claim 6, characterized in that: In step (1), the organic solvent is a good solvent for the polyester, and the good solvent is a mixture of one or more selected from tetrahydrofuran, chloroform, ethyl acetate and dichloromethane; In step (2), the dispersant is a mixture of one or more selected from polyvinyl pyrrolidone, polyethylene glycol, polyvinyl alcohol and polyacrylamide; the poor solvent for the polyester is selected from water and a mixture of water and methanol or ethanol.

8. The method for preparing an injectable dermal filler according to claim 6, characterized in that: In step (4), the mass concentration of the modified solution is 0.5% to 3%; the volatile solvent is dichloromethane or a mixture of dichloromethane and an alcohol solvent or chloroform or a mixture of chloroform and an alcohol solvent; the alcohol solvent is methanol, ethanol or isopropanol; the mixing ratio of the dichloromethane / chloroform to the alcohol solvent is (1 to 9):(1 to 9).

9. The method for preparing an injectable dermal filler according to claim 6, characterized in that: In step (6), the freeze-drying temperature is -40°C to -38°C, the freeze-drying time is 12 to 48 hours, and the vacuum degree is 0.5 to 1.0 Pa.

10. Use of an injectable skin filler according to any one of claims 1 to 5 in medical cosmetology, characterized in that: The injectable skin filler is a lyophilized agent and is diluted with phosphate buffer before injection.

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