Alginic acid-based facial filler as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biological medicines and medical cosmetic materials, and discloses an alginic acid-based facial filler which comprises the following components in percentage by mass: 13-26% of an alginic acid-based material, 40-43% of polylactic acid microspheres and 34-44% of a freeze-drying protective agent, the alginic acid-based material comprises sodium alginate and oxidized sodium alginate, the G / M ratio of the sodium alginate to the oxidized sodium alginate is 3: 1-1: 1, and the mass ratio of the oxidized sodium alginate to the sodium alginate is 2: 1-1: 2. According to the preparation method, an alginic acid-based material with biodegradable stimulation characteristics is used, aldehyde groups of oxidized sodium alginate can generate Schiff base reaction with amino groups on the tissue surface so as to contribute to anchoring a target part, and the alginic acid-based material and polylactic acid microspheres can act on cells to promote collagen secretion; the face filler also has timely filling performance and gradient degradation performance. The invention also provides a preparation method of the alginic acid-based facial filler.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine and medical cosmetic materials, and in particular relates to an alginate-based facial filler and a preparation method and application thereof. Background Art

[0002] With the development of biomaterials science and clinical medical technology, the plastic surgery industry has shifted from surgical beauty to minimally invasive non-surgical beauty, which has promoted the rapid development of minimally invasive injection beauty products and provided some beauty methods with less trauma and quick recovery.

[0003] At present, conventional tissue filling products include hyaluronic acid, collagen, hydroxyapatite, polylactic acid and autologous fat particles, etc. These products have good filling effects and certain biocompatibility. Conventional hyaluronic acid and collagen have a short degradation cycle. This problem can be solved by cross-linking or adding polymer materials with a longer degradation time, but the degree of cross-linking is difficult to determine. If the degree of cross-linking is small, the effect of extending the cross-linking time cannot be achieved; if the degree of cross-linking is large, it will increase the resistance during use, and the hydrophilicity is also poor, which may also cause inflammatory reactions, leading to nodules or granulomas, etc. In addition, there is a safety risk of cross-linking agent residues. Polymer materials have poor hydrophilicity and weak cell affinity, and there is also a risk of causing inflammation. Now sodium hyaluronate fillers are easily squeezed by muscles in dynamic expression areas (such as apple muscles and nasolabial folds), resulting in displacement or diffusion of fillers, resulting in a "steamed" appearance, easy displacement, poor stability, and short duration.

[0004] The existing technology cannot meet the requirements of timely filling and continuous stimulation of collagen regeneration to supplement the defect without regression. Therefore, it has become an urgent problem to develop and provide a filling material that can be used for medical cosmetology, which has the characteristics of gradient degradation, continuous stimulation of collagen regeneration, and good compatibility with tissues. Summary of the invention

[0005] The present invention aims to provide an alginate-based facial filler and a preparation method and application thereof, so as to solve at least one of the above-mentioned technical problems.

[0006] According to a first aspect of the present invention, an alginate-based facial filler is provided, wherein the alginate-based facial filler comprises, by mass percentage, 13% to 26% alginate-based material, 40% to 43% polylactic acid microspheres, and 34% to 44% lyoprotectant; wherein the alginate-based material comprises sodium alginate and oxidized sodium alginate, the G / M ratios of sodium alginate and oxidized sodium alginate are both 3:1 to 1:1, and the mass ratio of oxidized sodium alginate to sodium alginate is 2:1 to 1:2; Oxidized sodium alginate is prepared by the following method: sodium alginate is dispersed in anhydrous ethanol to prepare a sodium alginate suspension, and then a sodium periodate solution is added to the sodium alginate suspension, reacting for 18 to 32 hours under light-proof conditions, and ethylene glycol is added to terminate the reaction to obtain a reaction mixture, and the reaction mixture is purified and freeze-dried to obtain the product.

[0007] The alginate-based facial filler of the present invention has good raw material compatibility with tissues, and the alginate-based material has biodegradable stimulating properties, and acts on cells with polylactic acid microspheres to stimulate collagen production. In addition, oxidized sodium alginate is obtained by oxidation of sodium alginate, and some hydroxyl groups in its molecules are oxidized to aldehyde groups. The presence of aldehyde groups makes more active sites appear on the molecular chain, and these sites are more susceptible to attacks by external factors such as moisture, oxygen, enzymes, etc., so that the molecular chain is more easily broken, resulting in oxidized sodium alginate being easier to degrade than sodium alginate. Therefore, the two can be used together as facial filler carrier materials to achieve gradient degradation at the filling site due to different degradation rates.

[0008] Moreover, the alginate-based material with high G content can act dually with polylactic acid microspheres on macrophages to promote fibroblasts to produce collagen, thereby promoting the repair of damaged tissues, and can be biodegraded into non-toxic and harmless small molecules during metabolism in the body.

[0009] In some embodiments, the mass volume ratio of sodium alginate to anhydrous ethanol may be 1:4 to 1:6. Specifically, 4 to 6 mL of anhydrous ethanol is required to be added to each 1 g of sodium alginate for dispersion.

[0010] In some embodiments, in the sodium periodate solution, the concentration of sodium periodate may be 6-20 wt %, and the molar ratio of ethylene glycol to sodium periodate in the sodium periodate solution may be 1:1.

[0011] In some embodiments, the molar ratio of sodium periodate to sodium alginate monomer units may be 20% to 100%. For example, the molar ratio of sodium periodate to sodium alginate monomer units may be 20%, 40%, 60%, 80% or 100%.

[0012] In some embodiments, the reaction mixture purification and freeze drying may include the following steps: adding the reaction mixture to anhydrous ethanol, precipitating a precipitate, filtering, drying the precipitate, dialyzing it with water for 24 to 72 hours, and freeze drying the liquid in the dialysis bag. Specifically, the reaction mixture can be purified using the above method to remove small molecule impurities such as unreacted sodium periodate and ethylene glycol.

[0013] In some embodiments, the volume ratio of the reaction mixture to anhydrous ethanol can be 1:4 to 1:6.

[0014] In some embodiments, the precipitate can be dried by vacuum drying the precipitate at 35-45°C.

[0015] In some embodiments, the molecular weight of sodium alginate can be 8-12 kDa.

[0016] In some embodiments, the polylactic acid microspheres can be selected from at least one of poly-L-lactic acid solid smooth microspheres, poly-L-lactic acid porous microspheres, poly-racemic lactic acid solid smooth microspheres, poly-racemic lactic acid porous microspheres, poly-racemic lactic acid-poly-L-lactic acid solid smooth microspheres, and poly-racemic lactic acid-poly-L-lactic acid porous microspheres.

[0017] In some embodiments, the particle sizes of the polylactic acid microspheres are in three gradient ranges of 15 μm to 25 μm, 25 μm to 35 μm, and 35 μm to 50 μm, and the mass ratio of the microspheres in the three particle size gradient ranges is 3:2:1 to 2:1:1.

[0018] In some embodiments, the polylactic acid microspheres include first polylactic acid microspheres, second polylactic acid microspheres, and third polylactic acid microspheres, the particle size of the first polylactic acid microspheres may be 15 μm to 25 μm, the particle size of the second polylactic acid microspheres may be 25 μm to 35 μm, the particle size of the third polylactic acid microspheres may be 35 μm to 50 μm, and the mass ratio of the first polylactic acid microspheres, the second polylactic acid microspheres, and the third polylactic acid microspheres may be 3:2:1 to 2:1:1. Thus, due to the presence of space gaps of different sizes, polylactic acid microspheres of different particle sizes can achieve a better filling effect, making the filling support better; moreover, polylactic acid microspheres of different particle sizes have different degradation rates, and small-size polylactic acid microspheres can be preferentially degraded to promote collagen regeneration and achieve a gradient degradation effect.

[0019] In some embodiments, the porosity of the polylactic acid microspheres may be 30% to 60%.

[0020] In some embodiments, the lyoprotectant can be selected from at least one of mannitol, trehalose, and polyethylene glycol.

[0021] According to a second aspect of the present invention, there is provided a method for preparing an alginate-based facial filler, comprising the following steps: S1. Add the alginate-based material into water for injection, stir evenly, and then add a lyophilization protective agent to dissolve to obtain a mobile phase; S2. Adding polylactic acid microspheres as microsphere particles suspended in the mobile phase into the mobile phase, and packaging and sterilizing after vacuum freeze-drying to obtain the product.

[0022] In some embodiments, the vacuum freeze drying procedure is as follows:

[0024] In some embodiments, the sterilization treatment method can be irradiation sterilization or sterilization using ethylene oxide.

[0025] According to a third aspect of the present invention, there is provided the use of the alginate-based facial filler in the preparation of medical cosmetic products or cosmetics, in particular, as a tissue damage repair product, a collagen regeneration stimulation product, or a facial filling product.

[0026] Compared with the prior art, the present invention has the following beneficial effects: (1) The alginate-based facial filler of the present invention uses a biodegradable alginate-based material as a facial filler carrier material, which can be slowly degraded into non-toxic and harmless small molecules during metabolism, and can stimulate collagen production like polylactic acid microspheres, thereby achieving the purpose of dual and gradient stimulation of collagen regeneration; (2) In the alginate-based facial filler of the present invention, the alginate-based material is composed of oxidized sodium alginate and sodium alginate. Oxidized sodium alginate is more easily degraded than sodium alginate. The combination of the two as a facial filler carrier material not only plays a supporting role but also can be degraded in a gradient manner; (3) In the alginate-based facial filler of the present invention, the aldehyde groups of the polyaldehyde-oxidized sodium alginate obtained by sodium periodate oxidation can react with the amino groups on the tissue surface to produce a Schiff base reaction, thereby producing a chemical bonding effect, which is not easy to shift at the injection filling site and can better anchor the target site; (4) The alginate-based facial filler of the present invention has excellent tissue damage repair performance, collagen regeneration stimulation performance, timely filling performance and gradient degradation performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a Fourier transform infrared spectrum of oxidized sodium alginate prepared in Example 1 of the present invention; wherein SA represents sodium alginate, and OSA represents oxidized sodium alginate; Figure 2 These are microscope images of cells at 0 h, 12 h and 24 h in the scratch healing experiment of Experimental Example 1 of the present invention. DETAILED DESCRIPTION

[0028] The present invention is further described in detail below in conjunction with the embodiments. The examples are only for explanation and are not intended to limit the present invention in any way. Unless otherwise specified, the raw materials and reagents used in the examples are conventional products that can be obtained commercially; the experimental methods in the examples where specific conditions are not specified are usually carried out according to conventional conditions in the art or according to the conditions recommended by the manufacturer.

[0029] The sodium alginate powder used in the present invention is commercially available, and the purity of the sodium alginate is 85%, wherein the content of guluronic acid is 50% to 80%. In the following examples, "vigorous stirring" means that the stirring speed is 1200 to 1800 rpm. It should be noted that "G / M" refers to the ratio of guluronic acid (G segment) to mannuronic acid (M segment) in the sodium alginate molecule.

[0030] Example 1 This embodiment provides a method for preparing an alginate-based facial filler, comprising the following steps: (1) Preparation of oxidized sodium alginate: 10 g of sodium alginate powder (G / M=3:1) was dispersed in 50 mL of anhydrous ethanol to prepare a sodium alginate suspension; 10 g of sodium periodate was dissolved in 50 mL of water to prepare a sodium periodate solution; the sodium periodate solution was added to the sodium alginate suspension at a molar ratio of sodium periodate to sodium alginate monomer unit of 60%, and the mixture was stirred magnetically at room temperature in the dark for about 24 h, and then ethylene glycol was added in an amount equal to the molar amount of sodium periodate. The reaction was terminated after about 15 min to obtain a reaction mixture; The obtained reaction mixture was poured into vigorously stirred anhydrous ethanol, the volume ratio of the reaction mixture to anhydrous ethanol was 1:5, and a precipitate was precipitated, which was then filtered and dried in vacuo at 40°C to obtain a solid powder. The obtained solid powder was dialyzed with distilled water for 24 h to remove unreacted sodium periodate and small molecular impurities such as ethylene glycol, and finally the liquid in the dialysis bag was freeze-dried to obtain oxidized sodium alginate (G / M=3:1).

[0031] The prepared oxidized sodium alginate was detected by Fourier transform infrared spectrometer (instrument model: Nicoleti S50). The test results are as follows: Figure 1 As shown. Figure 1 It can be seen that oxidized sodium alginate (OSA) has a higher peak at 1735 cm-1 than sodium alginate (SA). -1 The stretching vibration peak of the C=O double bond in the aldehyde group was detected, indicating that oxidized sodium alginate was successfully prepared.

[0032] (2) Preparation of alginate-based facial filler: In terms of mass percentage, the alginate-based material is 13.5%, the poly-L-lactic acid solid smooth microspheres (particle size of 30 μm, porosity of 40%) and the lyophilization protective agent mannitol is 43.9%, wherein the alginate-based material includes oxidized sodium alginate (G / M=3:1) and sodium alginate (G / M=3:1). The oxidized sodium alginate (G / M=3:1) and sodium alginate (G / M=3:1) are added to the injection water at a mass ratio of 2:1 and stirred evenly, and then the lyophilization protective agent is added to dissolve to obtain the mobile phase; Finally, the poly-L-lactic acid solid smooth microspheres are added to the above mobile phase as microsphere particles suspended in the mobile phase, and are vacuum freeze-dried according to the procedure in Table 1, and then packaged and sterilized to obtain the alginate-based facial filler.

[0033] Table 1 Vacuum freeze drying procedure

[0034] Example 2 This embodiment provides a method for preparing an alginate-based facial filler, comprising the following steps: (1) Preparation of oxidized sodium alginate: 10 g of sodium alginate powder (G / M=3:1) was dispersed in 50 mL of anhydrous ethanol to prepare a sodium alginate suspension; 10 g of sodium periodate was dissolved in 50 mL of water to prepare a sodium periodate solution; the sodium periodate solution was added to the sodium alginate suspension at a molar ratio of sodium periodate to sodium alginate monomer unit of 60%, and the mixture was stirred magnetically at room temperature in the dark for about 24 h, and then ethylene glycol was added in an amount equal to the molar amount of sodium periodate. The reaction was terminated after about 15 min to obtain a reaction mixture; The obtained reaction mixture was poured into vigorously stirred anhydrous ethanol, the volume ratio of the reaction mixture to anhydrous ethanol was 1:5, and a precipitate was precipitated, which was then filtered and dried in vacuo at 40°C to obtain a solid powder. The obtained solid powder was dialyzed with distilled water for 24 h to remove unreacted sodium periodate and small molecular impurities such as ethylene glycol, and finally the liquid in the dialysis bag was freeze-dried to obtain oxidized sodium alginate (G / M=3:1).

[0035] (2) Preparation of alginate-based facial filler: In terms of mass percentage, the alginate-based material is 13.5%, the poly-L-lactic acid porous microspheres (particle size of 30 μm, porosity of 50%) and the lyophilization protective agent mannitol is 43.9%, wherein the alginate-based material includes oxidized sodium alginate (G / M=3:1) and sodium alginate (G / M=3:1). The oxidized sodium alginate (G / M=3:1) and sodium alginate (G / M=3:1) are added to the injection water at a mass ratio of 2:1 and stirred evenly, and then the lyophilization protective agent is added to dissolve to obtain the mobile phase; Finally, the poly-L-lactic acid porous microspheres are added to the mobile phase as microsphere particles suspended in the mobile phase, and are vacuum freeze-dried according to the procedure in Table 1, and then packaged and sterilized to obtain the alginate-based facial filler.

[0036] Example 3 This embodiment provides a method for preparing an alginate-based facial filler, comprising the following steps: (1) Preparation of oxidized sodium alginate: 10 g of sodium alginate powder (G / M=3:1) was dispersed in 50 mL of anhydrous ethanol to prepare a sodium alginate suspension; 10 g of sodium periodate was dissolved in 50 mL of water to prepare a sodium periodate solution; the sodium periodate solution was added to the sodium alginate suspension at a molar ratio of sodium periodate to sodium alginate monomer unit of 60%, and the mixture was stirred magnetically at room temperature in the dark for about 24 h, and then ethylene glycol was added in an amount equal to the molar amount of sodium periodate. The reaction was terminated after about 15 min to obtain a reaction mixture; The obtained reaction mixture was poured into vigorously stirred anhydrous ethanol, the volume ratio of the reaction mixture to anhydrous ethanol was 1:5, and a precipitate was precipitated, which was then filtered and dried in vacuo at 40°C to obtain a solid powder. The obtained solid powder was dialyzed with distilled water for 24 h to remove unreacted sodium periodate and small molecular impurities such as ethylene glycol, and finally the liquid in the dialysis bag was freeze-dried to obtain oxidized sodium alginate (G / M=3:1).

[0037] (2) Preparation of alginate-based facial filler: In terms of mass percentage, the alginate-based material is prepared according to 13.5% alginate-based material, 42.6% poly(lactic acid) solid smooth microspheres (particle size of 30 μm, porosity of 40%), and 43.9% lyophilization protective agent mannitol, wherein the alginate-based material includes oxidized sodium alginate (G / M=3:1) and sodium alginate (G / M=3:1). The oxidized sodium alginate (G / M=3:1) and sodium alginate (G / M=3:1) are added to the injection water at a mass ratio of 2:1 and stirred evenly, and then the lyophilization protective agent is added to dissolve to obtain the mobile phase; Finally, the poly(racemic) lactic acid solid smooth microspheres were added to the mobile phase as microsphere particles suspended in the mobile phase, and vacuum freeze-dried according to the procedure in Table 1, and then packaged and sterilized to obtain the alginate-based facial filler.

[0038] Example 4 This embodiment provides a method for preparing an alginate-based facial filler, comprising the following steps: (1) Preparation of oxidized sodium alginate: 10 g of sodium alginate powder (G / M=3:1) was dispersed in 50 mL of anhydrous ethanol to prepare a sodium alginate suspension; 10 g of sodium periodate was dissolved in 50 mL of water to prepare a sodium periodate solution; the sodium periodate solution was added to the sodium alginate suspension at a molar ratio of sodium periodate to sodium alginate monomer unit of 60%, and the mixture was stirred magnetically at room temperature in the dark for about 24 h, and then ethylene glycol was added in an amount equal to the molar amount of sodium periodate. The reaction was terminated after about 15 min to obtain a reaction mixture; The obtained reaction mixture was poured into vigorously stirred anhydrous ethanol, the volume ratio of the reaction mixture to anhydrous ethanol was 1:5, and a precipitate was precipitated, which was then filtered and dried in vacuo at 40°C to obtain a solid powder. The obtained solid powder was dialyzed with distilled water for 24 h to remove unreacted sodium periodate and small molecular impurities such as ethylene glycol, and finally the liquid in the dialysis bag was freeze-dried to obtain oxidized sodium alginate (G / M=3:1).

[0039] (2) Preparation of alginate-based facial filler: In terms of mass percentage, the alginate-based material is 13.5%, the poly(lactic acid) porous microspheres (particle size 30 μm, porosity 50%) are 42.6%, and the lyophilization protective agent mannitol is 43.9%. The alginate-based material includes oxidized sodium alginate (G / M=3:1) and sodium alginate (G / M=3:1). The oxidized sodium alginate (G / M=3:1) and sodium alginate (G / M=3:1) are added to the injection water at a mass ratio of 2:1 and stirred evenly, and then the lyophilization protective agent is added to dissolve to obtain the mobile phase; Finally, the poly(racemic) lactic acid porous microspheres were added to the mobile phase as microsphere particles suspended in the mobile phase, and vacuum freeze-dried according to the procedure in Table 1, and then packaged and sterilized to obtain the alginate-based facial filler.

[0040] Comparative Example 1 This comparative example provides a method for preparing an alginate-based facial filler, comprising the following steps: (1) Preparation of oxidized sodium alginate: Disperse 10 g of sodium alginate powder (G / M=1:2) in 50 mL of anhydrous ethanol to prepare a sodium alginate suspension; dissolve 10 g of sodium periodate in 50 mL of water to prepare a sodium periodate solution; add the sodium periodate solution to the sodium alginate suspension at a molar ratio of sodium periodate to sodium alginate monomer unit of 60%, and stir magnetically at room temperature in the dark for about 24 h; then add ethylene glycol in an amount equal to the molar amount of sodium periodate, and terminate the reaction after about 15 min to obtain a reaction mixture; The obtained reaction mixture was poured into vigorously stirred anhydrous ethanol, the volume ratio of the reaction mixture to anhydrous ethanol was 1:5, and a precipitate was precipitated, which was then filtered and dried in vacuo at 40°C to obtain a solid powder. The obtained solid powder was dialyzed with distilled water for 24 h to remove unreacted sodium periodate and small molecular impurities such as ethylene glycol, and finally the liquid in the dialysis bag was freeze-dried to obtain oxidized sodium alginate (G / M=1:2).

[0041] (2) Preparation of alginate-based facial filler: In terms of mass percentage, the alginate-based material is 13.5%, the poly-L-lactic acid solid smooth microspheres (particle size of 30 μm, porosity of 50%) and the lyophilization protective agent mannitol is 43.9%, wherein the alginate-based material includes oxidized sodium alginate (G / M=1:2) and sodium alginate (G / M=1:2). The oxidized sodium alginate (G / M=1:2) and sodium alginate (G / M=1:2) are added to the injection water at a mass ratio of 2:1 and stirred evenly, and then the lyophilization protective agent is added to dissolve to obtain the mobile phase; Finally, the poly-L-lactic acid solid smooth microspheres are added to the above mobile phase as microsphere particles suspended in the mobile phase, and are vacuum freeze-dried according to the procedure in Table 1, and then packaged and sterilized to obtain the alginate-based facial filler.

[0042] Experimental Example 1 In order to verify whether the alginate-based facial filler of the present invention achieves the expected effect, the alginate-based facial filler of Examples 1 to 4 and Comparative Example 1 was subjected to a macrophage and fibroblast co-culture experiment to examine the promotion of collagen secretion.

[0043] 1. Preparation of Conditioned Medium The conditioned medium is the culture supernatant produced by the co-culture of M0, M1 and M2 macrophages with the scaffold. The specific preparation method of the culture supernatant is as follows: in the presence of 2×10 4 The cells / well were inoculated at a density of 1.54 cells / well in a 48-well plate covered with the material. After 48 h of co-culture, the supernatant of the culture medium (CM) was collected, centrifuged and sterilized by filtration using a 0.22 μm sterile microporous filter membrane for later use.

[0044] 2. Co-culture group (1) Add 5 mL of physiological saline to the alginate-based facial filler. After the alginate-based facial filler is completely dissolved, the mixture is mixed with the culture medium at a mass ratio of 1:10 to obtain a mixed culture medium. M0, M1, and M2 macrophages are cultured at a rate of 1×10 5 cells / well were inoculated into Transwell and mixed culture medium was added after culturing for 24 h. At the same time as macrophages were inoculated, 1×10 5 cells / well of fibroblasts, after culturing for 24 hours, the Transwell was placed in a 24-well plate for co-culture, and PCR detection was performed after culturing for 3 days.

[0045] (2) Scratch healing: 1×10 4The cells were inoculated into a 6-well plate at a density of 10 cells / well and incubated overnight until the cells reached 90% confluence; then a sterile 200 μL pipette tip was used to scratch the bottom of the well plate to form a cell-free strip in the center of the monolayer of cells; the original culture medium was discarded and washed with PBS solution to remove non-adherent cells and cell debris. The conditioned medium of M1 cells was added and then incubated in a cell culture incubator, and the scratches were photographed under a microscope at 0 h, 12 h, and 24 h.

[0046] 3. Experimental results The PCR test results of M0, M1 and M2 macrophages after co-culture with fibroblasts for 3 days are shown in Tables 2 and 3. As can be seen from Table 2, after the alginate-based facial filler of the comparative example was added to macrophages and fibroblasts for co-culture for 3 days, the expression values ​​of type I collagen in M0 and M2 macrophages were higher than those in Examples 1 to 4. As can be seen from Table 3, the expression values ​​of type III collagen in M0, M1 and M2 macrophages obtained by co-culture with Examples 1 to 4 were higher than those in Comparative Example 1, indicating that in the case of co-culture of macrophages and fibroblasts, oxidized sodium alginate and sodium alginate with high G content as raw materials have excellent performance in promoting macrophages to secrete type III collagen, thereby contributing to tissue damage repair.

[0047] Table 2 COL-1 (type Ⅰ collagen expression) in co-culture group

[0048] Table 3 COL-3 (type III collagen expression) in co-culture group

[0049] In the scratch healing experiment, the microscopic images of cells at 0h, 12h and 24h are as follows: Figure 2 As shown. Figure 2 It can be seen that the scratch width observed at 24 h was significantly lower than that observed at 0 h and 12 h, indicating that the alginate-based facial filler of the present invention can promote the enhanced migration ability of fibroblasts in a 24-hour scratch healing experiment, help the surrounding tissues to gather to the injured site, and ultimately achieve tissue repair.

[0050] The above experimental results show that the alginate-based facial filler of the present invention has excellent performance in promoting collagen secretion and potential in promoting tissue repair.

[0051] The above are only some embodiments of the present invention. For those skilled in the art, several modifications and improvements can be made without departing from the creative concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. Alginate-based facial filler, characterized in that In terms of mass percentage, it includes 13% to 26% alginate-based material, 40% to 43% polylactic acid microspheres and 34% to 44% lyophilization protective agent; The alginate-based material includes sodium alginate and oxidized sodium alginate, the G / M ratio of the sodium alginate and the oxidized sodium alginate is 3:1-1:1, and the mass ratio of oxidized sodium alginate to sodium alginate is 2:1-1:2; The oxidized sodium alginate is prepared by the following method: dispersing sodium alginate in anhydrous ethanol to prepare a sodium alginate suspension, then adding a sodium periodate solution to the sodium alginate suspension, reacting for 18 to 32 hours under light-proof conditions, adding ethylene glycol to terminate the reaction, obtaining a reaction mixture, purifying the reaction mixture, and freeze-drying the reaction mixture to obtain the obtained product.

2. The alginate-based facial filler according to claim 1, characterized in that The concentration of sodium periodate in the sodium periodate solution is 6-20 wt %, the molar ratio of ethylene glycol to sodium periodate in the sodium periodate solution is 1:1, and the molar ratio of sodium periodate to sodium alginate monomer units is 20%-100%.

3. The alginate-based facial filler according to claim 2, characterized in that The mass volume ratio of the sodium alginate to anhydrous ethanol is 1:4-1:

6.

4. The alginate-based facial filler according to claim 2, characterized in that The purification and freeze-drying of the reaction mixture comprises the following steps: adding the reaction mixture into anhydrous ethanol, precipitating a precipitate, filtering, drying the precipitate, dialyzing it with water for 24 to 72 hours, and freeze-drying the liquid in the dialysis bag.

5. The alginate-based facial filler according to any one of claims 1 to 4, characterized in that The particle sizes of the polylactic acid microspheres are in three gradient ranges of 15 μm to 25 μm, 25 μm to 35 μm, and 35 μm to 50 μm, and the mass ratio of the microspheres in the three particle size gradient ranges is 3:2:1 to 2:1:

1.

6. The alginate-based facial filler according to claim 5, characterized in that The porosity of the polylactic acid microspheres is 30% to 60%.

7. The alginate-based facial filler according to claim 5, characterized in that The lyophilization protective agent is selected from at least one of mannitol, trehalose and polyethylene glycol.

8. The method for preparing the alginate-based facial filler according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1, adding the alginate-based material to water for injection and stirring, and then adding a lyophilization protective agent to dissolve to obtain a mobile phase; S2. Adding polylactic acid microspheres as microsphere particles suspended in the mobile phase into the mobile phase, and packaging and sterilizing after vacuum freeze-drying to obtain the product.

9. The method for preparing the alginate-based facial filler according to claim 8, characterized in that: The procedure of the vacuum freeze drying is as follows: 。 10. Use of the alginate-based facial filler according to any one of claims 1 to 7 in the preparation of medical cosmetic products or cosmetics.

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