An injection type medical cosmetic facial filler composition gel and a preparation method and application thereof

Abstract

The application discloses an injection type medical and cosmetic facial filler composition gel and a preparation method and application thereof, and belongs to the technical field of biomedical materials; the composition gel comprises a combined gel matrix and polycaprolactone microspheres, wherein the combined gel matrix comprises an injection aqueous solution, sodium carboxymethyl cellulose and human recombinant collagen; the composition gel mixes the combined gel matrix and the polycaprolactone microspheres according to a specific ratio; the amino acid residues of the human recombinant collagen in the combined gel matrix not only serve as a binding site of a cell surface receptor, improve the cell recognition and adhesion capacity of the polycaprolactone microspheres, but also organically combine with the sodium carboxymethyl cellulose, improve the durability and biocompatibility of the shaping effect of the human recombinant collagen at an injection site; the prepared composition gel has good flowability, high elastic modulus and high dynamic viscosity, and can meet the expected mechanical and rheological properties of a cosmetic and plastic facial filler.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to an injectable facial filler composition gel for medical aesthetics, its preparation method, and its application. Background Technology

[0002] In recent years, materials used for soft tissue filling in the cosmetic surgery market can be divided into two categories. One category is absorbable materials, including but not limited to collagen, hyaluronic acid, polycaprolactone (PCL), hydroxyapatite, and polylactic acid (PLLA). These materials can be gradually degraded and absorbed by the human body, and have a high safety profile, but their effects are limited in duration. The other category is non-absorbable materials, such as silicone and polymethyl methacrylate microspheres (PMMA). Although they provide permanent filling effects, they pose risks of long-term complications such as foreign body reactions and granulomas, which limits their clinical application.

[0003] Sodium carboxymethyl cellulose (CMC) is a water-soluble cellulose derivative commonly used as a gel matrix or thickener in cosmetic fillers. The carboxymethyl groups on its molecular chain endow the material with excellent hydrophilicity and rheological properties, enabling it to form a stable three-dimensional network structure and enhancing the viscoelasticity and post-injection shape retention of the filler. However, the application of sodium carboxymethyl cellulose has the following problems: First, its rheological properties are insufficient; low-concentration CMC gels have low elastic modulus and weak support, while high concentrations result in excessive viscosity, making injection difficult. Second, CMC alone only acts as a physical filler carrier and cannot actively promote tissue regeneration and repair.

[0004] Polycaprolactone (PCL), as a biodegradable polyester, has a long degradation cycle and can effectively stimulate collagen regeneration, achieving gradual shaping. However, injecting PCL microspheres can cause a clinical foreign body inflammatory response, ultimately leading to microsphere embedding, fibrosis, and collagen deposition, thus achieving a "gradual" filling effect. Long-term tissue regeneration requires consideration of cell and protein adhesion to the microsphere surface; microspheres with hydrophilic surfaces can promote protein and cell adhesion. However, PCL microspheres are hydrophobic and lack cell binding sites, therefore stimulating collagen production requires a certain amount of time.

[0005] Among products used for soft tissue filling, a widely used example is Ellansé, whose core components are polycaprolactone microspheres and carboxymethyl cellulose (CMC) gel carriers. CMC provides an immediate filling effect, while the PCL microspheres achieve long-lasting shaping by stimulating collagen regeneration. For example, Chinese patent publication CN114146020A, filed on February 10, 2022, discloses an injectable cosmetic product, its preparation method, and its application. This injectable cosmetic product includes biodegradable microspheres and CMC. Na gel, the CMC Na-supported gels allow microspheres to be carried out in CMC. The sodium gel provides long-term uniform suspension, maintaining the independent three-dimensional structure of each microsphere. This allows the microspheres to be evenly distributed in the body after injection, significantly reducing the chances of lumps and foreign body granulomas. However, this cosmetic product relies solely on the physical suspension effect of the CMC gel to ensure microsphere dispersion, failing to address the difficulty of cell adhesion caused by the hydrophobic surface of the PCL microspheres. Consequently, it cannot provide immediate collagen repair capabilities, resulting in a delayed onset of action.

[0006] Chinese Patent CN115282337A, filed on September 30, 2022, discloses a pre-dispersed composition of polycaprolactone (PCL) microspheres and a PCL injection gel prepared therefrom. In this pre-dispersed composition, the PCL microspheres maintain their spherical shape, have a smooth surface, good dispersibility, and a reduced degradation rate. This reduces air bubbles during mixing, which helps ensure product quality stability and reduces the likelihood of nodules and granulomas caused by uneven dispersion of the microspheres after in vivo injection. Although this invention reduces microsphere aggregation through a pre-dispersion process, it does not alter the hydrophobic surface properties of the PCL microspheres. Cell recognition and attachment efficiency remains low, and the collagen deposition rate is not fundamentally improved. Furthermore, the composition does not introduce biocompatible components to neutralize the foreign body reaction of the microspheres, and relying on process optimization cannot completely eliminate the risk of granulomas.

[0007] In addition, the above-mentioned injectable gel containing sodium carboxymethyl cellulose and polycaprolactone microspheres faces two main problems in industrial production: 1) To ensure the uniform dispersion of polycaprolactone microspheres in the injectable gel, mechanical stirring and mixing for a long time is required. The shear force and heat generated during the stirring process will cause the polycaprolactone microspheres to break and shrink, making it impossible to guarantee the integrity of the microspheres; 2) To avoid the deposition of polycaprolactone microspheres in the gel matrix over time, the dynamic viscosity of the gel is relatively high, which increases the extrusion force and makes it difficult to inject clinically. If the viscosity is reduced, the polycaprolactone microspheres will deposit, resulting in heterogeneous areas at the injection site.

[0008] Human recombinant collagen is a type of collagen synthesized through genetic engineering. Its structure is highly similar to that of natural human collagen, exhibiting excellent biocompatibility, low immunogenicity, and cell regeneration-promoting functions. Compared to traditional animal-derived collagen, recombinant technology avoids the risk of viral contamination and can precisely design and regulate collagen molecular fragments, making it easier for the skin to absorb and activate fibroblasts to secrete collagen, thereby repairing the dermal structure and improving wrinkles and sagging.

[0009] For example, Chinese patent CN113384748A, filed on April 29, 2021, discloses a collagen dermal implant and its preparation method. The implant uses a chemical cross-linking agent to cross-link fermented collagen, giving it physical filling capabilities. This collagen dermal implant has no immunotoxicity and good biocompatibility, making it suitable as a tissue filler in cosmetic medicine. However, due to the presence of collagenase in the human body, collagen fillers are easily degraded by collagenase, resulting in a lack of lasting wrinkle-reducing effects and requiring repeated injections to maintain the cosmetic effect.

[0010] Although current composite fillers attempt to combine immediate filling with long-term regeneration, existing solutions still suffer from three main contradictions. First, functional limitation: CMC only provides temporary support and cannot compensate for the immediate repair function of collagen. Second, biocompatibility is a bottleneck: the hydrophobic surface of PCL microspheres delays tissue integration and may exacerbate inflammatory responses. Third, insufficient process stability: the microsphere-gel system is prone to phase separation during sterilization and storage, making it difficult to meet the requirements of industrial production. Therefore, there is an urgent need to develop a novel composite filler that integrates the immediate repair capabilities of human recombinant collagen with the long-term shaping function of PCL. This filler should improve the cell affinity of PCL microspheres, accelerate tissue regeneration, and optimize the rheological properties of the gel matrix to ensure long-term uniform dispersion and clinical injectability of the microspheres. Summary of the Invention

[0011] To address the problems existing in the prior art, this invention provides an injectable facial filler composition gel for cosmetic purposes, its preparation method, and its application. The composition gel comprises a combined gel matrix and polycaprolactone microspheres. The combined gel matrix contains sodium carboxymethyl cellulose and human recombinant collagen. The introduction of collagen not only provides timely collagen replenishment but also improves the fluidity of high-concentration sodium carboxymethyl cellulose. This allows the polycaprolactone microspheres to be uniformly dispersed in the gel matrix, significantly reducing the pushing force of the composition gel and solving the problem of needle clogging caused by uneven dispersion. The injectable facial filler composition gel exhibits good dispersibility, low pushing force, and good fluidity, possessing the mechanical and rheological properties expected of facial fillers used in cosmetic surgery.

[0012] The technical solution of the present invention is as follows:

[0013] One of the objectives of this invention is to provide an injectable facial filler composition gel for medical aesthetics, comprising 30-70 parts by weight of a combined gel matrix and 10-70 parts by weight of polycaprolactone microspheres;

[0014] The composite gel matrix includes an aqueous solution for injection, sodium carboxymethyl cellulose, and human recombinant collagen, wherein the human recombinant collagen is one or more combinations of type I human recombinant collagen, type III human recombinant collagen, and type XVII human recombinant collagen;

[0015] The amino acid sequence of type I human recombinant collagen is shown in SEQ ID No. 1;

[0016] The amino acid sequences of type III human recombinant collagen are shown in SEQ ID No. 2 and SEQ ID No. 3;

[0017] The amino acid sequence of type XVII human recombinant collagen is shown in SEQ ID No. 4;

[0018] The average particle size of the polycaprolactone microspheres is 20-70 μm.

[0019] Furthermore, it also includes 0.1-10 parts of polyol;

[0020] The polyol is any one or a combination of sorbitol, glycerol, mannitol, propylene glycol, butylene glycol, maltitol, and lactitol.

[0021] Furthermore, it also includes 0.05-1 part of the anesthetic lidocaine.

[0022] Furthermore, the injectable facial filler composition gel has a pH value of 6.5-8.0 and possesses the following characteristics:

[0023] At a frequency of 0.1 Hz and a temperature of 25°C, the loss tangent G” / G’ is 0.25-0.75;

[0024] At a frequency of 0.1 Hz and a temperature of 25°C, the elastic modulus G' is 100-1500 Pa;

[0025] At a frequency of 0.1 Hz and a temperature of 25°C, the viscosity is 40-1400 Pa·s.

[0026] Furthermore, the combined gel matrix has an osmotic pressure of 280-650 mOsm / kg and a shear viscosity range of 40000-400000 mPa·s.

[0027] Further, the aqueous solution for injection is a sodium chloride solution or a phosphate buffer solution with a mass concentration of 0.9%, wherein the phosphate buffer solution includes any one or more combinations of disodium hydrogen phosphate, dipotassium hydrogen phosphate, diammonium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, and ammonium dihydrogen phosphate.

[0028] The pH of the aqueous solution for injection is 6.0-8.0, and the osmotic pressure is 280-650 mOsm / kg.

[0029] Furthermore, the sodium carboxymethyl cellulose has a viscosity-average molecular weight of 700-1200 KD and a degree of substitution ranging from 0.65 to 1.0; the sodium carboxymethyl cellulose accounts for 1%-5% of the total weight of the aqueous solution for injection.

[0030] Furthermore, the sodium carboxymethyl cellulose can be replaced by any one or more of cellulose ethers such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, or cyanoethyl cellulose.

[0031] Furthermore, the molecular weight of the human recombinant collagen is 10-300KD; the human recombinant collagen accounts for 0.01%-1% of the total weight of the aqueous solution for injection.

[0032] Furthermore, the injectable facial filler composition gel includes any one or more combinations of antibacterial agents, antioxidants, or mineral salts.

[0033] The second objective of this invention is to provide a method for preparing an injectable facial filler composition gel for cosmetic use, comprising the following steps:

[0034] S1. Dissolve human recombinant collagen and anesthetic in prepared water for injection, sprinkle in sodium carboxymethyl cellulose, mechanically stir to ensure that sodium carboxymethyl cellulose is in full contact with the above solution, use a vacuum stirrer to stir evenly and eliminate bubbles, and let stand for 2-8 hours to form a gel.

[0035] S2. Add polyol to the mixed solution stirred in S1, mechanically stir to mix the material evenly, use a vacuum stirrer to stir evenly and eliminate bubbles, and obtain the combined gel matrix.

[0036] S3. Use the prepared injectable aqueous solution to uniformly disperse polycaprolactone microspheres, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate air bubbles to obtain the injectable medical aesthetic facial filler composition gel.

[0037] Furthermore, the mechanical stirring speed mentioned in the above steps is 100-1500 r / min, and the stirring time is 1-10 min. Manual stirring can be used as an auxiliary method depending on the mixing situation.

[0038] Furthermore, the vacuum stirring degassing machine used in the above steps can have a stirring speed of 1500-2500 r / min and a stirring time of 1-15 min, thereby simultaneously achieving the purpose of uniform material and eliminating air bubbles.

[0039] Furthermore, the above-mentioned method for mixing materials combines mechanical stirring, assisted manual stirring, and vacuum stirring to reduce the total mixing time and minimize the impact of shear force and heat generated during the stirring process on the integrity of polycaprolactone microspheres.

[0040] The third objective of this invention is to provide an application of an injectable facial filler composition gel in the preparation of injectable medical aesthetic products.

[0041] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0042] 1. This invention discloses for the first time an injectable facial filler composition gel for medical aesthetics. Addressing the problems of delayed cell adhesion and rapid collagen degradation caused by the hydrophobic surface of polycaprolactone (PCL) microspheres, as well as the lack of bioactivity in carboxymethyl cellulose (CMC) gels in existing technologies, this invention creatively introduces recombinant human collagen as a key bridging component. The amino acid residues of collagen provide specific binding sites for cells, directly modifying the surface of PCL microspheres, transforming the hydrophobic interface into a hydrophilic bioactive interface, accelerating fibroblast migration and collagen deposition, and overcoming the slow onset of action of PCL. Simultaneously, the sodium carboxymethyl cellulose gel mechanism provides immediate physical support, collagen promotes immediate dermal repair, and sodium carboxymethyl cellulose drives long-term regeneration, forming a three-stage sequential effect of "filling-repair-regeneration".

[0043] 2. The injectable facial filler composition gel designed in this invention features good dispersibility, low extrusion force, and good flowability. Firstly, sodium carboxymethyl cellulose (CCC) raw material is selected based on its degree of substitution and molecular weight, and glycerol is added to regulate lubricity, ensuring consistent rheological properties in each batch of gel. The introduction of human recombinant collagen improves the viscosity and flowability of high-concentration CCC, resulting in excellent dispersibility and low extrusion force in the composition gel. Polycaprolactone microspheres are directly added to the CCC gel matrix containing human recombinant collagen, and a combination of mechanical and vacuum stirring achieves uniform dispersion of the microspheres, shortening the mixing time and process, and avoiding microsphere damage caused by prolonged mechanical stirring. Furthermore, the CCC and human recombinant collagen in the injectable facial filler composition gel are organically combined. The high biocompatibility of the human recombinant collagen neutralizes the foreign body reaction of the polycaprolactone microspheres, significantly reducing the risk of granulomas. This not only improves the gel's persistence at the injection site but also enhances the composition's biocompatibility and reduces inflammatory reactions. In addition, the introduction of human recombinant collagen can adjust the elastic modulus of the composition gel. By adding different proportions of human recombinant collagen to the composition gel in which sodium carboxymethyl cellulose and polycaprolactone microspheres are in equal proportions, composition gels with low, medium and high elastic modulus can be provided for clinical use to meet the cosmetic needs of different parts of the face.

[0044] 3. This invention solves the technical problems of uneven matrix dispersion, lack of cell recognition sites on the hydrophobic surface of polycaprolactone microspheres, and rapid degradation and short-lasting cosmetic effects of collagen products alone. The gel matrix formed by collagen and sodium carboxymethyl cellulose in this composition gel has a more regular pore structure and stronger fluidity compared to sodium carboxymethyl cellulose alone, reducing the extrusion force of the filler and significantly improving the dispersibility of the filler microspheres. Furthermore, different amounts of collagen have different modulating effects on the rheological properties of the filler, allowing for the provision of products with low, medium, and high elastic moduli to meet the cosmetic needs of different areas by adjusting the amount of collagen added without changing the ratio of polycaprolactone microspheres to sodium carboxymethyl cellulose.

[0045] 4. The injectable facial filler composition gel of this invention possesses excellent rheological properties and superior biocompatibility, meeting the mechanical properties, rheological properties, and extrusion force requirements for facial fillers used in clinical cosmetic surgery. This composition gel can be injected into subcutaneous tissue, deep tissues, and the periosteum to achieve filling and support functions. This invention also provides a method for preparing this injectable facial filler composition gel. After vacuum degassing, the composition gel can be directly filled for large-scale industrial production. No two-phase region appears during industrial vacuum filling, maintaining a stable, uniform single phase for a long period. Viscosity fluctuations are minimal after moist heat sterilization, meeting the requirements of aseptic production lines. Even after moist heat sterilization, the polycaprolactone microspheres remain uniformly dispersed in the composition gel for a long period, making the composition easy for clinical injection. Attached Figure Description

[0046] Figure 1 This is a SEM image of the gel prepared from sodium carboxymethyl cellulose No. 1 during the performance test of this invention.

[0047] Figure 2 This is a pore structure diagram of the CMC-C composition gel prepared in Comparative Example 1 during the performance test of this invention;

[0048] Figure 3 This is a pore structure diagram of the CMC-CP composition gel prepared in Example 1 of the present invention for performance testing.

[0049] Figure 4 The results of elastic modulus testing for the CMC-CP composition gels prepared in Examples 3-10 of this invention are as follows;

[0050] Figure 5 The extrusion force of the CMC-CP composition gel prepared in Example 5 of the present invention is used in the performance test of the present invention.

[0051] Figure 6This is a comparison diagram of the changes in the microsphere structure of the CMC-CP composition gel prepared in Example 11 of the present invention before and after stirring and recovery. Detailed Implementation

[0052] The present invention will be further described below with reference to preferred embodiments. The endpoints and any values ​​of the ranges disclosed in the present invention are not limited to the precise ranges or values. These ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be regarded as specifically disclosed herein.

[0053] Unless otherwise specified, the experimental methods in the following embodiments are conventional methods, performed in accordance with the techniques or conditions described in the literature in this field or in accordance with the product instructions.

[0054] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0055] The CMC-Na used in the following examples was purchased from Sigma.

[0056] In the following examples, unless otherwise stated, sodium carboxymethyl cellulose (CMC-Na) is abbreviated as CMC; recombinant human collagen (COL) is abbreviated as C; polycaprolactone microspheres (PCL) are abbreviated as P; a gel containing sodium carboxymethyl cellulose and polycaprolactone microspheres is abbreviated as CMC-P gel, a gel containing sodium carboxymethyl cellulose, recombinant human collagen and polycaprolactone microspheres is abbreviated as CMC-CP gel, and so on.

[0057] Solution A is physiological saline, which is an aqueous solution for injection with a final sodium chloride concentration of 0.09 g / L.

[0058] The concentrations of sodium carboxymethyl cellulose and recombinant human collagen are both percentages of the weight of the aqueous solution for injection.

[0059] The average particle size of the polycaprolactone microspheres is between 25 and 50 μm, and the concentration of the polycaprolactone microspheres is a percentage of the total weight of the gel composition.

[0060] Example 1

[0061] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0062] S1. Dissolve 0.1g COL in 67.0g solution A, evenly sprinkle in 2.8g CMC, mechanically stir for 3min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 2h to form a gel;

[0063] S2. Use a vacuum stirrer to remove air bubbles from the mixed solution stirred in S1 for 5 minutes to obtain the combined gel matrix.

[0064] S3. Disperse 30.2g of PCL microspheres evenly with 30.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0065] Example 2

[0066] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0067] S1. Dissolve 0.2g COL in 67.0g solution A, sprinkle 2.8g CMC evenly, stir mechanically for 2min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 3h to form a gel;

[0068] S2. Use a vacuum stirrer to remove air bubbles from the mixed solution stirred in S1 for 5 minutes to obtain the combined gel matrix.

[0069] S3. Disperse 30.2g of PCL microspheres evenly with 30.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0070] Example 3

[0071] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0072] S1. Dissolve 0.05g COL in 67.0g solution A, sprinkle 2.8g CMC evenly, stir mechanically for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 4h to form a gel;

[0073] S2. Use a vacuum stirrer to remove air bubbles from the mixed solution stirred in S1 for 5 minutes to obtain the combined gel matrix.

[0074] S3. Disperse 30.2g of PCL microspheres evenly with 30.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0075] Example 4

[0076] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0077] S1. Dissolve 0.2g COL in 62.6g solution A, evenly sprinkle in 3.0g CMC, mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 5h to form a gel;

[0078] S2. Use a vacuum stirrer to remove air bubbles from the mixed solution stirred in S1 for 5 minutes to obtain the combined gel matrix.

[0079] S3. Disperse 34.4g of PCL microspheres evenly with 34.4g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0080] Example 5

[0081] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0082] S1. Dissolve 0.1g COL in 65.8g solution A, evenly sprinkle in 3.0g CMC, mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 6h to form a gel;

[0083] S2. Add 1g of glycerol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0084] S3. Disperse 30.2g of PCL microspheres evenly with 30.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0085] Example 6

[0086] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0087] S1. Dissolve 0.2g COL in 58.8g solution A, evenly sprinkle in 3.0g CMC, mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 7h to form a gel;

[0088] S2. Add 1g of sorbitol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0089] S3. Disperse 40.2g of PCL microspheres evenly with 40.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0090] Example 7

[0091] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0092] S1. Dissolve 0.2g COL in 56.8g solution A, evenly sprinkle in 3.0g CMC, mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 7h to form a gel;

[0093] S2. Add 3g of mannitol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0094] S3. Disperse 40.2g of PCL microspheres evenly with 40.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0095] Example 8

[0096] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0097] S1. Dissolve 0.2g COL in 54.8g solution A, evenly sprinkle in 3.0g CMC, mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 8h to form a gel;

[0098] S2. Add 5g of butanediol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0099] S3. Disperse 40.2g of PCL microspheres evenly with 40.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0100] Example 9

[0101] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0102] S1. Dissolve 0.3g COL in 65.8g solution A, evenly sprinkle in 3.0g CMC, mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 4h to form a gel;

[0103] S2. Add 1.0g of glycerol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0104] S3. Disperse 30.2g of PCL microspheres evenly with 30.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0105] Example 10

[0106] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0107] S1. Dissolve 0.2g COL in 65.8g solution A, evenly sprinkle in 3.0g CMC, mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 4h to form a gel;

[0108] S2. Add 1.0g of glycerol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0109] S3. Disperse 30.2g of PCL microspheres evenly with 30.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0110] Example 11

[0111] This embodiment provides a method for preparing an injectable facial filler composition gel CMC-CP:

[0112] S1. Dissolve 0.1g COL in 65.8g solution A, evenly sprinkle in 3.0g CMC, mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution, stir with a vacuum stirrer for 5min, and let stand for 4h to form a gel;

[0113] S2. Add 1.0g of glycerol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0114] S3. Disperse 30.2g of PCL microspheres evenly with 30.2g of solution A, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0115] Example 12

[0116] This embodiment provides an injectable facial filler composition gel CMC-CP for cosmetic medical use, the preparation method of which is shown below:

[0117] S1. Dissolve 0.1g of type I COL with a molecular weight of 10 KD and an amino acid sequence as shown in SEQ ID No. 1 in 65.8g of disodium hydrogen phosphate solution with pH 6.0 and osmotic pressure of 280 mOsm / kg. Evenly sprinkle 3.0g of methylcellulose with a viscosity-average molecular weight of 700KD and a degree of substitution of 0.65. Mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution. Stir for 5min using a vacuum stirrer and let stand for 6h to form a gel.

[0118] S2. Add 1g of propylene glycol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0119] S3. Using 30.2g of disodium hydrogen phosphate, uniformly disperse 30.2g of PCL microspheres with an average particle size of 30μm, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0120] The injectable facial filler composition gel CMC-CP prepared in this embodiment has a pH value of 6.5-8.0 and has the following characteristics:

[0121] At a frequency of 0.1 Hz and a temperature of 25°C, the loss tangent G” / G’ is 0.25-0.75;

[0122] At a frequency of 0.1 Hz and a temperature of 25°C, the elastic modulus G' is 100-1500 Pa;

[0123] At a frequency of 0.1 Hz and a temperature of 25°C, the viscosity is 40-1400 Pa·s.

[0124] Example 13

[0125] This embodiment provides an injectable facial filler composition gel CMC-CP for cosmetic medical use, the preparation method of which is shown below:

[0126] S1. Dissolve 0.1g of type III COL with a molecular weight of 100 KD and an amino acid sequence as shown in SEQ ID No. 2 in 65.8g of dipotassium hydrogen phosphate solution with pH 7.0 and osmotic pressure of 450 mOsm / kg. Evenly sprinkle 3.0g of ethyl cellulose with a viscosity-average molecular weight of 900 KD and a degree of substitution of 0.75. Mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution. Stir for 5min using a vacuum stirrer and let stand for 6h to form a gel.

[0127] S2. Add 1g of propylene glycol and 0.5g of lidocaine to the mixed solution stirred in S1. Stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0128] S3. Disperse 30.2g of PCL microspheres with an average particle size of 20μm evenly using 30.2g of dipotassium hydrogen phosphate, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0129] Example 14

[0130] This embodiment provides an injectable facial filler composition gel CMC-CP for cosmetic medical use, the preparation method of which is shown below:

[0131] S1. Dissolve 0.1g of type III COL with a molecular weight of 300 KD and an amino acid sequence as shown in SEQ ID No. 3 in 65.8g of diammonium hydrogen phosphate solution with pH 7.5 and osmotic pressure of 500 mOsm / kg. Evenly sprinkle 3.0g of hydroxypropyl cellulose with a viscosity-average molecular weight of 900 KD and a degree of substitution of 0.8. Mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution. Stir for 5min using a vacuum stirrer and let stand for 6h to form a gel.

[0132] S2. Add 1g of maltitol and 0.8g of lidocaine to the mixed solution stirred in S1. Stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0133] S3. Using 30.2g of diammonium hydrogen phosphate, uniformly disperse 30.2g of PCL microspheres with an average particle size of 40μm, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0134] The injectable facial filler composition gel CMC-CP prepared in this embodiment has a pH value of 6.5-8.0 and has the following characteristics:

[0135] Example 15

[0136] This embodiment provides an injectable facial filler composition gel CMC-CP for cosmetic medical use, the preparation method of which is shown below:

[0137] S1. Dissolve 0.1g of sodium carboxymethyl cellulose (COL) with a molecular weight of 110 KD and an amino acid sequence as shown in SEQ ID No. 4 in 65.8g of sodium dihydrogen phosphate solution with pH 8.0 and osmotic pressure of 650 mOsm / kg. Evenly sprinkle 3.0g of hydroxypropyl methyl cellulose with a viscosity-average molecular weight of 1200 KD and a degree of substitution of 1.0. Mechanically stir for 1 min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution. Stir for 5 min using a vacuum stirrer to remove bubbles, and let stand for 6 h to form a gel.

[0138] S2. Add 1g of lactitol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0139] S3. Using 30.2g of sodium dihydrogen phosphate, uniformly disperse 30.2g of PCL microspheres with an average particle size of 50μm, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP.

[0140] The injectable facial filler composition gel CMC-CP prepared in this embodiment has a pH value of 6.5-8.0 and has the following characteristics:

[0141] At a frequency of 0.1 Hz and a temperature of 25°C, the loss tangent G” / G’ is 0.25-0.75;

[0142] At a frequency of 0.1 Hz and a temperature of 25°C, the elastic modulus G' is 100-1500 Pa;

[0143] At a frequency of 0.1 Hz and a temperature of 25°C, the viscosity is 40-1400 Pa·s.

[0144] Example 16

[0145] This embodiment provides a method for applying an injectable facial filler composition gel CMC-CP:

[0146] S1. Dissolve 0.1g of type XVII COL with a molecular weight of 200 KD and an amino acid sequence as shown in SEQ ID No.4 in 65.8g of ammonium dihydrogen phosphate solution with pH 8.0 and osmotic pressure of 650 mOsm / kg. Evenly sprinkle 3.0g of cyanoethyl cellulose with a viscosity-average molecular weight of 1200 KD and a degree of substitution of 1.0. Mechanically stir for 1min to ensure that sodium carboxymethyl cellulose is fully in contact with the solution. Stir for 5min using a vacuum stirrer and let stand for 6h to form a gel.

[0147] S2. Add 1g of lactitol to the mixed solution stirred in S1, stir mechanically to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate bubbles for 5 minutes to obtain the combined gel matrix.

[0148] S3. Using 30.2g of ammonium dihydrogen phosphate, uniformly disperse 30.2g of PCL microspheres with an average particle size of 70 μm, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to degas and eliminate bubbles for 10 minutes to obtain the injectable medical aesthetic facial filler composition gel CMC-CP, with a pH value of 7.2, an elastic modulus G' of 161.35 Pa at 0.1 Hz frequency and 25℃, a viscosity of 817.53 Pa·s, and a loss tangent value G" / G' of 0.45;

[0149] S4. Clean, disinfect, and mark the target injection area. After equilibrating the prepared CMC-CP gel at room temperature, load it into a 1mL syringe and install a 27G needle.

[0150] S5. Using linear tunneling injection technology, insert the needle along the fold direction to the middle or deep layer of the dermis, and slowly and evenly inject the gel with an extrusion force of 11N. After injection, gently massage to distribute the gel evenly.

[0151] S6. Observe the filling effect immediately and record the degree of improvement. Observe the filling durability, changes in skin texture and adverse reactions at 1 week, 1 month, 3 months and 6 months after injection.

[0152] Comparative Example 1

[0153] This comparative example provides a method for preparing the composition gel CMC-C:

[0154] 2.8g CMC and 0.1g COL were added to 100g solution A under slow stirring and stirred thoroughly for 4 hours to obtain a clear and transparent solution or gel. The solution was then stirred and degassed using a vacuum stirrer to remove air bubbles, thus obtaining the gel CMC-C of the composition.

[0155] Comparative Example 2

[0156] This comparative example provides a method for preparing the composition gel CMC-P:

[0157] 2.7g of CMC was added to 59.8g of solution A under slow stirring, and stirred thoroughly for 4 hours to obtain a clear and transparent solution or gel. The solution was then stirred and degassed using a vacuum stirrer to remove air bubbles. 40.2g of PCL microspheres were uniformly dispersed in 40.2g of solution A, and then added to the prepared gel matrix. The mixture was stirred until homogeneous and formed a uniform phase. The solution was then stirred and degassed using a vacuum stirrer to remove air bubbles, thus obtaining the CMC-P composition gel.

[0158] Comparative Example 3

[0159] This comparative example provides a method for preparing the composition gel CMC-P:

[0160] 2.8g of CMC was added to 59.8g of solution A under slow stirring, and stirred thoroughly for 4 hours to obtain a clear and transparent solution or gel. The solution was then stirred and degassed using a vacuum stirrer to remove air bubbles. 40.2g of PCL microspheres were uniformly dispersed in 40.2g of solution A, and then added to the prepared gel matrix. The mixture was stirred until homogeneous and formed a uniform phase. The solution was then stirred and degassed using a vacuum stirrer to remove air bubbles, thus obtaining the CMC-P composition gel.

[0161] Comparative Example 4

[0162] This comparative example provides a method for preparing the composition gel CMC-P:

[0163] 3.0g of CMC was added to 59.8g of solution A under slow stirring, and stirred thoroughly for 4 hours to obtain a clear and transparent solution or gel. The solution was then stirred and degassed using a vacuum stirrer to remove air bubbles. 40.2g of PCL microspheres were uniformly dispersed in 40.2g of solution A, and then added to the prepared gel matrix. The mixture was stirred until homogeneous and formed a uniform phase. The solution was then stirred and degassed using a vacuum stirrer to remove air bubbles, thus obtaining the CMC-P composition gel.

[0164] Performance testing

[0165] 1. Testing of gelation effect, pore size range, and uniformity of CMC-Na gel

[0166] Four different grades of CMC-Na raw materials were selected from the market, and the viscosity-average molecular weight of CMC-Na of each grade was determined. The determination method is as follows:

[0167] (1) Accurately weigh 25 mg of CMC Na raw material was dissolved in 80 mL of 0.2 mol / L sodium chloride solution and the solution was left to stand at 50 °C for 16 h.

[0168] (2) Transfer the solution completely and make up to 100 mL. Use an Ubbelohde viscometer with an inner diameter of 0.55 mm and 0.2 mol / L sodium chloride solution as blank control solution to determine the viscosity according to the viscosity determination method (method 2) of General Chapter 0633 of Part IV of the Chinese Pharmacopoeia (2020 edition).

[0169] (3) Calculate the intrinsic viscosity [η] according to equations (1) and (2).

[0170] [η]= lnη r / c (1)

[0171] η r = T / T0 (2)

[0172] T is the elution time of the test solution in seconds, T0 is the elution time of the blank in seconds, and C is the concentration of the test solution.

[0173] (4) Calculate the viscosity-average molecular weight (M) according to formula (3), Mark Houwink formula:

[0174] [η]=KM α Equation (3)

[0175] When sodium carboxymethyl cellulose (CMC) dissolved in 0.2 mol / L sodium chloride solution, K = 0.043 mL / g and α = 0.74. The viscosity-average molecular weight of the four CMC-Na specifications was determined. The degree of substitution and pH value of the CMC-Na gel were obtained from the product label. The viscosity-average molecular weight and degree of substitution values ​​of the four CMC-Na gel specifications are shown in the table below:

[0176]

[0177] (5) Four specifications of CMC-Na gel were prepared. The preparation steps are as follows:

[0178] 1) Pour dihydrogen phosphate and sodium hydroxide into a beaker to prepare a pH of 6.0. Add 8.0g of PBS buffer and stir.

[0179] 2) Add 2.5g of CMC-Na to 100g of solution A while stirring slowly, ensuring the powder and buffer solution are fully in contact and stirring for 2 seconds. 5 hours, until no lumps or unmixed powder are seen in the gel;

[0180] 3) Add a certain amount (0.9% of the final product filler) to the gel. Add 1.1 wt.% glycerol and stir thoroughly for about 10 minutes;

[0181] 4) Vacuum stirring and degassing machine was used to remove air bubbles, and four specifications of CMC were obtained. Na gel.

[0182] The formulations of CMC-Na gels of various specifications are as follows:

[0183]

[0184] (6) Take 10-20 ml of gel sample into a sample bottle, invert the sample bottle and observe the flowability of the gel. Take 10-20 ml of gel and freeze-dry it. Detect the pore size range and uniformity of the gel by scanning electron microscopy (SEM).

[0185] The inversion experiment results showed that gels prepared with sodium carboxymethyl cellulose (CMC) No. 3 and No. 4 flowed immediately after inversion and did not form a gel; gels prepared with sodium carboxymethyl cellulose (CMC) No. 1 and No. 2 did not show obvious flow after inversion; SEM results showed that the gel prepared with sodium carboxymethyl cellulose (CMC) No. 1 had uniform pores and a pore size of approximately 100 nm (see...). Figure 1 ).

[0186] (7) Compared with the pore structure of sodium carboxymethyl cellulose gel No. 1, the pore structure of Comparative Example 1, which incorporates human recombinant collagen, is more regular (see Comparative Example 1). Figure 2Furthermore, Example 1, which incorporated collagen and polycaprolactone microspheres, also exhibited a regular pore structure, and the microspheres were observed to be uniformly distributed within the gel without any microsphere aggregation (see Example 1). Figure 3 ).

[0187] 2. Viscosity test

[0188] Since increased viscosity limits the spread of gel in soft tissue and also contributes to the volume increase effect, viscosity is an important parameter of filler compositions. Therefore, the viscosity of Examples 1-10 and Comparative Examples 1-4 was measured (at 25°C, frequencies from 0.1 Hz to 10 Hz, plate size PP35, gap size 2 μm, Hacker rotational rheometer).

[0189] It was found that at 25°C and 0.1 Hz, the combined gel viscosity of Comparative Examples 3-4 and Examples 1-10 was equal to or greater than 200 Pa·s; with the same CMC and PCL microsphere content, increasing the COL content could improve the flowability of the composition gel and reduce the viscosity of the composition (Example 1, Example 2).

[0190]

[0191] 3. Elastic modulus test

[0192] Since the elastic modulus affects the lifting ability of fillers, maintaining the elastic modulus is quite important. In this embodiment, the elastic modulus and loss tangent of the composite gel are measured, and the elastic modulus of the composite gel and the single gel are compared.

[0193] Modulus measurements were performed on Examples 1-10 and Comparative Examples 1-4 (at 25°C, frequency from 0.1Hz to 1Hz, plate size PP35, gap size 2μm, Hacker rotational rheometer).

[0194] It was found that at 25°C and 0.1 Hz, the elastic modulus of the combined gels in Comparative Examples 3-4 and Examples 1-10 were all equal to or greater than 100 Pa, exhibiting good elastic properties. The loss tangent values ​​of the combined gels in Examples 3-10 were between 0.25 and 0.75, indicating that the combined gels possess both good liquid flowability and solid plasticity, making them suitable as a cosmetic filler (see...). Figure 4 Comparative examples 9-11 revealed that the amount of human recombinant collagen added can provide composite gels with different elastic moduli while ensuring the same proportion of sodium carboxymethyl cellulose and polycaprolactone microspheres.

[0195]

[0196] 4. Extrusion force test

[0197] The composite gel in this invention is an injectable gel, and extrusion force is crucial for clinical use. Therefore, the extrusion force of the composite gel of Example 5, pre-filled into a syringe, was tested. It was found that with a 1 mL syringe, a 27G needle, and an extrusion rate adjusted to 12 mm / min, the injection force was 11 N (see...). Figure 5 The addition of COL and glycerol reduces the extrusion force of cellulose ether gels, resulting in a low injection force for the gel composition, which can significantly reduce the difficulty of injection for physicians.

[0198] 5. Microsphere Integrity Testing

[0199] The sample from Example 11 was washed with water for injection, lyophilized, and then subjected to SEM electron microscopy to observe the effect of the stirring method on the polycaprolactone microspheres. Figure 6 As shown, the microspheres recovered in Example 11 have an intact structure, and no breakage or shrinkage was found compared with the sample before stirring, indicating that the stirring method used in this invention preserves the integrity of the microspheres.

[0200] The experimental data provided in the above embodiments fully demonstrate that the filling composition described in this invention can be used in clinical cosmetic medicine, providing durability and lifting capabilities.

[0201] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent modifications made based on the content of the present invention specification and drawings, or direct or indirect applications in related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. An injectable facial filler composition gel for cosmetic purposes, characterized in that, The product comprises, by weight, 30-70 parts of a combined gel matrix and 10-70 parts of polycaprolactone microspheres, as well as 0.1-10 parts of polyol and 0.05-1 part of lidocaine, an anesthetic. The composite gel matrix includes an aqueous solution for injection, sodium carboxymethyl cellulose, and human recombinant collagen, wherein the human recombinant collagen is one or more combinations of type I human recombinant collagen, type III human recombinant collagen, and type XVII human recombinant collagen; The amino acid sequence of type I human recombinant collagen is shown in SEQ ID No. 1; The amino acid sequences of type III human recombinant collagen are shown in SEQ ID No. 2 and SEQ ID No. 3; The amino acid sequence of type XVII human recombinant collagen is shown in SEQ ID No. 4; The average particle size of the polycaprolactone microspheres is 20-70 μm. The sodium carboxymethyl cellulose has a viscosity-average molecular weight of 700-1200 kDa and a degree of substitution ranging from 0.65 to 1.0; the sodium carboxymethyl cellulose accounts for 1%-5% of the total weight of the aqueous solution for injection. The molecular weight of the recombinant human collagen is 10-300 kDa; the recombinant human collagen accounts for 0.01%-1% of the total weight of the aqueous solution for injection; The preparation method of the injectable facial filler composition gel for medical aesthetics includes the following steps: S1. Dissolve human recombinant collagen and anesthetic in prepared water for injection, sprinkle in sodium carboxymethyl cellulose, mechanically stir to ensure that sodium carboxymethyl cellulose is in full contact with the above solution, use a vacuum stirrer to stir evenly and eliminate bubbles, and let stand for 2-8 hours to form a gel. S2. Add polyol to the mixed solution stirred in S1, mechanically stir to mix the material evenly, use a vacuum stirrer to stir evenly and eliminate bubbles, and obtain the combined gel matrix. S3. Use the prepared injectable aqueous solution to uniformly disperse polycaprolactone microspheres, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate air bubbles to obtain the injectable medical aesthetic facial filler composition gel.

2. The injectable facial filler composition gel for medical aesthetics according to claim 1, characterized in that, The polyol is any one or a combination of sorbitol, glycerol, mannitol, propylene glycol, butylene glycol, maltitol, and lactitol.

3. The injectable facial filler composition gel according to claim 1, characterized in that, The injectable facial filler composition has a gel pH of 6.5-8.0 and possesses the following characteristics: At a frequency of 0.1 Hz and a temperature of 25°C, the loss tangent G” / G’ is 0.25-0.75; At a frequency of 0.1 Hz and a temperature of 25°C, the elastic modulus G' is 100-1500 Pa; At a frequency of 0.1 Hz and a temperature of 25°C, the viscosity is 40-1400 Pa·s.

4. The injectable facial filler composition gel according to claim 1, characterized in that, The combined gel matrix has an osmotic pressure of 280-650 mOsm / kg and a shear viscosity range of 40000-400000 mPa·s.

5. The injectable facial filler composition gel according to claim 1, characterized in that, The aqueous solution for injection is a sodium chloride solution or a phosphate buffer solution with a mass concentration of 0.9%, wherein the phosphate buffer solution includes any one or more combinations of disodium hydrogen phosphate, dipotassium hydrogen phosphate, diammonium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, and ammonium dihydrogen phosphate. The pH of the aqueous solution for injection is 6.0-8.0, and the osmotic pressure is 280-650 mOsm / kg.

6. A method for preparing an injectable facial filler composition gel according to claim 1, characterized in that, Includes the following steps: S1. Dissolve human recombinant collagen and anesthetic in prepared water for injection, sprinkle in sodium carboxymethyl cellulose, mechanically stir to ensure that sodium carboxymethyl cellulose is in full contact with the above solution, use a vacuum stirrer to stir evenly and eliminate bubbles, and let stand for 2-8 hours to form a gel. S2. Add polyol to the mixed solution stirred in S1, mechanically stir to mix the material evenly, use a vacuum stirrer to stir evenly and eliminate bubbles, and obtain the combined gel matrix. S3. Use the prepared injectable aqueous solution to uniformly disperse polycaprolactone microspheres, add the combined gel matrix, mechanically stir to mix the material evenly, and use a vacuum stirrer to stir evenly and eliminate air bubbles to obtain the injectable medical aesthetic facial filler composition gel.

7. The application of the injectable facial filler composition gel according to claim 1 in the preparation of injectable medical aesthetic products.

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