A composite cosmetic filler containing a decellularized placental extract and a method of preparing the same

Abstract

This invention belongs to the field of biomedical materials technology, specifically relating to a composite cosmetic filler containing decellularized placental extract and its preparation method. The composite cosmetic filler containing decellularized placental extract of this invention comprises, by weight, 0.1-0.5 parts of decellularized placental extract, 0.05-0.1 parts of calcium alginate, 0.01-0.05 parts of mucopeptide, and 1-3 parts of hydrogel matrix material. The cosmetic filler obtained by this invention not only has a good filling effect but also high safety, durability, and anti-inflammatory and antioxidant activity.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically, it relates to a composite cosmetic filler containing decellularized placental extract and its preparation method. Background Technology

[0002] The placenta, also known as "Zi Che He," is a commonly used traditional Chinese medicine. It is a special tissue in viviparous mammals that provides nutrients to the fetus during pregnancy, allowing the embryo to grow. It is expelled during childbirth. Due to its unique barrier and endocrine functions, it has been valued since ancient times. Human placental extracts (HPE) refer to a series of small-molecule active substances extracted from the human placenta, including collagen, growth factors, amino acids, and bioactive peptides. Studies have found that HPE has multiple functions, including regulating the autonomic nervous and endocrine systems, enhancing immune function, anti-inflammatory effects, scavenging free radicals, promoting wound healing, liver detoxification, fatigue recovery, and increasing appetite. HPE can promote wound healing by regulating trypsin activity. It has a wide range of applications in the cosmetic field due to its significant antioxidant activity. It also contains a variety of cytokines and chemokines that are essential for the maintenance and differentiation of stem cells, and is therefore used to culture adult stem cells for translational research in regenerative medicine. It can also activate the expression of a series of genes related to skin function, thereby improving skin condition. Furthermore, it can improve LPS-induced lung inflammation in mice by activating anti-inflammatory factors.

[0003] Natural collagen, as a specific structural protein, has been widely recognized for its characteristics and advantages, and has further become one of the important raw materials for biomedical materials. Human placenta is rich in collagen, and contains multiple types of collagen, making it a valuable raw material for preparing natural medical collagen. Various types of natural medical collagen products prepared using human placenta are free from infectious diseases and overcome the risks of bacterial contamination or potential zoonotic diseases that may arise from using xenogeneic animal tissues or organs as raw materials. They also overcome the rejection reactions associated with xenograft use. Therefore, human placental extracts, especially placental collagen, have higher safety when used as cosmetic fillers. Summary of the Invention

[0004] The purpose of this invention is to provide a composite cosmetic filler containing decellularized placental extract and its preparation method. The composite cosmetic filler, as a biomedical material, belongs to a different type from cosmetics. The technical solution of this invention enables the obtained cosmetic filler to have higher safety, biocompatibility, and anti-inflammatory and antioxidant activity.

[0005] Therefore, the present invention provides the following technical solution.

[0006] One aspect of the present invention provides a composite cosmetic filler containing decellularized placental extract, wherein the raw materials comprise, by weight, 0.1 to 0.5 parts of decellularized placental extract, 0.05 to 0.1 parts of calcium alginate, 0.01 to 0.05 parts of mucopeptide, and 1 to 3 parts of hydrogel matrix material.

[0007] In a preferred embodiment of the present invention, the raw materials comprise, by weight, 0.1 to 0.5 parts of decellularized placental extract, 0.05 to 0.1 parts of calcium alginate, 0.01 to 0.05 parts of spirulina mucin peptide, and 1 to 3 parts of hydrogel matrix material.

[0008] In a preferred embodiment of the present invention, the raw materials comprise, by weight, 0.1 to 0.5 parts of decellularized placental extract, 0.05 to 0.1 parts of calcium alginate, 0.01 to 0.05 parts of snail mucin peptide, and 1 to 3 parts of hydrogel matrix material.

[0009] In a preferred embodiment of the present invention, the method for preparing the hydrogel matrix material includes:

[0010] Carboxymethyl cellulose calcium and hyaluronic acid were dissolved in water at a mass ratio of 1-2:5-10:100 to obtain a mixed solution of carboxymethyl cellulose calcium and hyaluronic acid.

[0011] The bifunctional coupling compound and silver nitrate were dissolved in a 60-80% (v / v) organic alcohol solution at a mass ratio of 1:0.01 to 0.05:100 and then sonicated to obtain a mixed solution of the silver ion-modified bifunctional coupling compound.

[0012] N-vinyl functional monomers and initiators were added to the obtained carboxymethyl cellulose calcium / hyaluronic acid mixed solution to carry out polymerization reaction. After the reaction was completed, a mixed solution of silver ion modified bifunctional coupling compound was added to the obtained product at a volume ratio of 1:0.1 to 0.3. The mixture was stirred continuously at 40 to 60°C for 2 to 4 hours, then allowed to stand for 8 to 12 hours. Finally, the mixture was filtered, and the resulting gel was washed and dried to obtain the hydrogel matrix material.

[0013] In a preferred embodiment of the present invention, the bifunctional coupling compound is selected from any one or a mixture of two or more of bis(succinimide) octanoate, bis(succinimide) adipate, and bis(succinimide) succinimide.

[0014] In a preferred embodiment of the present invention, the organic alcohol is selected from any one of ethanol, propanol, and propylene glycol.

[0015] In a preferred embodiment of the present invention, the ultrasonic conditions are: power 600-800W, time 30-60min.

[0016] In a preferred embodiment of the present invention, the functional monomer is selected from any one of N-vinylcaprolactam, N-vinylimidazole, and vinylpyrrolidone.

[0017] In a preferred embodiment of the present invention, the amount of the functional monomer added is 1 to 3 times the mass of hyaluronic acid.

[0018] In a preferred embodiment of the present invention, the initiator is selected from any one of ammonium persulfate, potassium persulfate, and sodium persulfate.

[0019] In a preferred embodiment of the present invention, the amount of the initiator added is 0.3 to 0.5% of the mass of the functional monomer.

[0020] In a preferred embodiment of the present invention, the composite cosmetic filler further comprises physiological saline, wherein the physiological saline content is 80 to 120 parts by weight.

[0021] By employing the above technical solution, the present invention has at least the following advantages:

[0022] 1. The composite cosmetic filler containing decellularized placental extract of the present invention not only has excellent filling and repair effects, but also can maintain the filling effect for a long time, making it a cosmetic repair material with great potential and application prospects. The preparation method of the present invention is simple and suitable for industrial production.

[0023] 2. This invention uses decellularized placental extract and mucinous peptides as the main active substances, supplemented with calcium alginate and a hydrogel matrix material. Using the hydrogel matrix material as a carrier, the decellularized placental extract and mucinous peptides are cross-linked onto the hydrogel matrix material under the cross-linking action of calcium alginate, thereby forming a stable polymer with a three-dimensional network structure. The main component of the decellularized placental extract is human placental collagen, which has good biocompatibility and is unlikely to cause rejection reactions. The mucinous peptides are small molecule peptides with anti-inflammatory and antioxidant activities. Therefore, the resulting filler not only has a good filling effect but also high safety, durability, and anti-inflammatory and antioxidant activities.

[0024] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, the preferred embodiments of the present invention are described in detail below. Attached Figure Description

[0025] Figure 1 Image of a decellularized placental extract;

[0026] Figure 2 The images show a comparison of the in vitro degradation of the composite cosmetic fillers in Examples 1-3 and Comparative Examples 1-4. Detailed Implementation

[0027] To make the technical means, creative features, achieved objectives, and effects of this invention readily understandable, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are merely some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0028] Unless otherwise specified, the preparation method of the human placental collagen, the main active substance in the decellularized placental extract used in the following examples, is based on patent CN103525890A, specifically as follows:

[0029] Fresh, intact human placentas obtained through disease screening and normal delivery were selected. The placental tissue was thoroughly cleaned and cut into small pieces, homogenized at low temperature, and centrifuged to remove the supernatant. The precipitate was washed with deionized water and centrifuged again, repeating this washing and centrifugation process four times until the supernatant was clear. The precipitate was then soaked in a 0.5 mol / L Tris-HCl buffer solution (pH 7.2) containing 10 mmol / L sodium ethylenediaminetetraacetate (Na2EDTA), 1.0 mol / L NaCl, and slowly stirred for 4 hours. After stirring, the precipitate was centrifuged, washed once more with Tris-HCl buffer, and centrifuged again. The final precipitate was then soaked in a digestion solution (pH 2.8, 0.5 mol / L acetic acid solution containing 5 g / L pepsin (activity 500 U / mg), with a mass five times the weight of the precipitate). The digestion was carried out under low temperature with continuous slow stirring for 12 hours. After enzyme inactivation, the precipitate was centrifuged to obtain the supernatant. The supernatant was filtered through a 0.22 μm microfiltration membrane, and the filtrate was collected. The filtrate was concentrated to obtain the decellularized placental extract. (Image of the extract is shown below.) Figure 1 As shown.

[0030] Unless otherwise specified, the spirulina mucin peptides used in the following examples are prepared as follows:

[0031] Spirulina powder was mixed with water at a mass ratio of 1:10 to prepare an algal solution, which was then homogenized under high pressure to obtain a broken-cell spirulina algal solution. The obtained broken-cell spirulina algal solution was placed in an ultrasonic reactor and ultrasonically extracted at 800W for 30 min to obtain an extract solution. The extract solution was centrifuged twice to obtain a supernatant. A compound enzyme preparation of papain (500 U / mg activity) and alkaline protease (500 U / mg activity) at a mass ratio of 1:1 was added to the supernatant and enzymatically hydrolyzed for 12 h. After enzymatic hydrolysis, the enzyme was inactivated, and the mixture was centrifuged to obtain a supernatant. The supernatant was filtered in a nanofiltration device with a molecular weight of 1000 Da, an operating pressure of 1.5 MPa, and a membrane flow rate controlled at 3 m / s. The filtrate was collected. The filtrate was concentrated and freeze-dried to obtain spirulina mucin peptides.

[0032] Unless otherwise specified, the snail mucin peptides used in the following examples are prepared according to patent CN103525890A, specifically as follows:

[0033] Snails of relatively large size and over four and a half months of age were selected and placed in a mucus extraction machine for extraction to obtain purified mucus. The snail meat was removed, its internal organs cleaned, and then homogenized. The resulting homogenate was mixed with the mucus at a volume ratio of 1:1 to obtain a mixed homogenate. The mixed homogenate was placed in an ultrasonic reactor and ultrasonically extracted at 800W for 30 minutes to obtain an extract solution. The extract solution was centrifuged twice to obtain the supernatant. Neutral protease (activity 600 U / mg) was added to the supernatant and enzymatically hydrolyzed for 12 hours. After enzymatic hydrolysis, the enzyme was inactivated, and then the mixture was centrifuged to obtain the supernatant. The supernatant was filtered in a nanofiltration device with a molecular weight of 1000 Da, an operating pressure of 1.5 MPa, and a membrane flow rate controlled at 3 m / s. The filtrate was collected. The filtrate was concentrated and freeze-dried to obtain snail mucus peptides.

[0034] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods.

[0035] Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0036] Example 1:

[0037] Preparation of hydrogel matrix material: Calcium carboxymethyl cellulose and hyaluronic acid (molecular weight 200,000 Da, CAS No.: 9004-61-9, Guangdong Wengjiang Chemical Reagent Co., Ltd.) were dissolved in water at a mass ratio of 1.5:7.5:100 to obtain a calcium carboxymethyl cellulose / hyaluronic acid mixed solution. Dispense bis(succinimide) octanoate and silver nitrate were dissolved in a 70% ethanol solution at a mass ratio of 1:0.03:100 and ultrasonicated at 700W for 45 min to obtain a silver ion-modified bis(succinimide) octanoate mixed solution. N-vinylcaprolactam (twice the mass of hyaluronic acid) and ammonium persulfate (0.4% of the mass of N-vinylcaprolactam) were added to the obtained carboxymethyl cellulose calcium / hyaluronic acid mixed solution and the polymerization reaction was carried out for 4 h. After the reaction was completed, a silver ion modified bis(succinimide) octanoate mixed solution was added to the obtained product at a volume ratio of 1:0.2 and stirred continuously at 50 °C for 3 h. After standing for 10 h, the mixture was finally filtered, and the obtained gel was washed and dried to obtain the hydrogel matrix material.

[0038] Preparation of composite cosmetic filler: According to the weight parts, mix 0.3 parts of decellularized placental extract, 0.075 parts of calcium alginate, 0.03 parts of mucopeptide, 2 parts of hydrogel matrix material and 100 parts of physiological saline evenly, and then sterilize and encapsulate.

[0039] Example 2:

[0040] Preparation of hydrogel matrix material: Calcium carboxymethyl cellulose and hyaluronic acid (molecular weight 200,000 Da, CAS No.: 9004-61-9, Guangdong Wengjiang Chemical Reagent Co., Ltd.) were dissolved in water at a mass ratio of 1:5:100 to obtain a calcium carboxymethyl cellulose / hyaluronic acid mixed solution. Dispense bis(succinimide) adipate and silver nitrate in a mass ratio of 1:0.05:100 in a 60% ethanol solution and sonicated at 600W for 60 min to obtain a silver ion-modified bis(succinimide) adipate mixed solution. N-vinylimidazole (1 times the mass of hyaluronic acid) and potassium persulfate (0.3% of the mass of N-vinylimidazole) were added to the obtained carboxymethyl cellulose calcium / hyaluronic acid mixed solution and the polymerization reaction was carried out for 3 h. After the reaction was completed, a silver ion modified bis(succinimide) adipate mixed solution was added to the obtained product at a volume ratio of 1:0.3 and stirred continuously at 60 °C for 2 h. After standing for 8 h, the mixture was finally filtered, and the obtained gel was washed and dried to obtain the hydrogel matrix material.

[0041] Preparation of composite cosmetic filler: According to the weight parts, mix 0.1 parts of decellularized placental extract, 0.05 parts of calcium alginate, 0.05 parts of mucopeptide, 1 part of hydrogel matrix material and 80 parts of physiological saline evenly, and then sterilize and encapsulate.

[0042] Example 3:

[0043] Preparation of hydrogel matrix material: Calcium carboxymethyl cellulose and hyaluronic acid (molecular weight 200,000 Da, CAS No.: 9004-61-9, Guangdong Wengjiang Chemical Reagent Co., Ltd.) were dissolved in water at a mass ratio of 2:10:100 to obtain a calcium carboxymethyl cellulose / hyaluronic acid mixed solution. Dispense bis(succinimide) succinate and silver nitrate in an 80% ethanol solution at a mass ratio of 1:0.01:100 and sonicated at 800W for 30 min to obtain a silver ion-modified bis(succinimide) succinate mixed solution. Vinylpyrrolidone (3 times the mass of hyaluronic acid) and sodium persulfate (0.5% of the mass of vinylpyrrolidone) were added to the obtained carboxymethyl cellulose calcium / hyaluronic acid mixed solution and the polymerization reaction was carried out for 5 h. After the reaction was completed, a silver ion modified bis(succinimide) succinate mixed solution was added to the obtained product at a volume ratio of 1:0.1 and stirred continuously at 40 °C for 4 h. After standing for 12 h, the mixture was finally filtered, and the obtained gel was washed and dried to obtain the hydrogel matrix material.

[0044] Preparation of composite cosmetic filler: According to the weight parts, mix 0.5 parts of decellularized placental extract, 0.1 parts of calcium alginate, 0.01 parts of mucopeptide, 3 parts of hydrogel matrix material and 120 parts of physiological saline evenly, and then sterilize and encapsulate.

[0045] Comparative Example 1: Mixed solution of bis(succinimide) octanoate without silver ion modification

[0046] Preparation of hydrogel matrix material: Carboxymethyl cellulose calcium and hyaluronic acid (molecular weight 200,000 Da, CAS No.: 9004-61-9, Guangdong Wengjiang Chemical Reagent Co., Ltd.) were dissolved in water at a mass ratio of 1.5:7.5:100 to obtain a carboxymethyl cellulose calcium / hyaluronic acid mixed solution. N-vinylcaprolactam (twice the mass of hyaluronic acid) and ammonium persulfate (0.4% of the mass of N-vinylcaprolactam) were added to the obtained carboxymethyl cellulose calcium / hyaluronic acid mixed solution, and a polymerization reaction was carried out for 4 hours. After the reaction was completed, the mixture was allowed to stand for 10 hours, and finally filtered. The resulting gel was washed and dried to obtain the hydrogel matrix material.

[0047] Preparation of composite cosmetic filler: According to the weight parts, mix 0.3 parts of decellularized placental extract, 0.075 parts of calcium alginate, 0.03 parts of mucopeptide, 2 parts of hydrogel matrix material and 100 parts of physiological saline evenly, and then sterilize and encapsulate.

[0048] Comparative Example 2: 2 parts without added hydrogel matrix material

[0049] Preparation of composite cosmetic filler: Mix 0.3 parts of decellularized placental extract, 0.075 parts of calcium alginate, 0.03 parts of mucin peptide and 100 parts of physiological saline by weight, and then sterilize and package.

[0050] Comparative Example 3: 0.03 parts without added mucin peptide

[0051] Preparation of hydrogel matrix material: Calcium carboxymethyl cellulose and hyaluronic acid (molecular weight 200,000 Da, CAS No.: 9004-61-9, Guangdong Wengjiang Chemical Reagent Co., Ltd.) were dissolved in water at a mass ratio of 1.5:7.5:100 to obtain a calcium carboxymethyl cellulose / hyaluronic acid mixed solution. Dispense bis(succinimide) octanoate and silver nitrate were dissolved in a 70% ethanol solution at a mass ratio of 1:0.03:100 and ultrasonicated at 700W for 45 min to obtain a silver ion-modified bis(succinimide) octanoate mixed solution. N-vinylcaprolactam (twice the mass of hyaluronic acid) and ammonium persulfate (0.4% of the mass of N-vinylcaprolactam) were added to the obtained carboxymethyl cellulose calcium / hyaluronic acid mixed solution and the polymerization reaction was carried out for 4 h. After the reaction was completed, a silver ion modified bis(succinimide) octanoate mixed solution was added to the obtained product at a volume ratio of 1:0.2 and stirred continuously at 50 °C for 3 h. After standing for 10 h, the mixture was finally filtered, and the obtained gel was washed and dried to obtain the hydrogel matrix material.

[0052] Preparation of composite cosmetic filler: Mix 0.3 parts of decellularized placental extract, 0.075 parts of calcium alginate, 2 parts of hydrogel matrix material and 100 parts of physiological saline by weight, and then sterilize and encapsulate.

[0053] Comparative Example 4: 2 parts without hydrogel matrix material and 0.03 parts with mucin peptide.

[0054] Preparation of composite cosmetic filler: Mix 0.3 parts of decellularized placental extract, 0.075 parts of calcium alginate and 100 parts of physiological saline by weight, and then sterilize and package.

[0055] Experiment 1: In vitro degradation test

[0056] Referring to GB16886 Biological Evaluation of Medical Devices, the composite cosmetic fillers prepared in Examples 1-3 and Comparative Examples 1-4 were placed in sterile PBS buffer (pH 7.2) and incubated at 37°C to observe degradation. The mass ratio of the samples was measured at 1, 3, 6, 9, 12, 15, and 18 months. For measurement, the sample was centrifuged at 5000g for 15 min, the supernatant was discarded, and the precipitate was washed three times with purified water. The final precipitate was then lyophilized, and its mass ratio was calculated. The results are shown in Table 1. Figure 2 .

[0057] Mass ratio (%) = Mass of sample after degradation / Mass of sample before degradation × 100%

[0058] Table 1 Comparison of in vitro degradation

[0059]

[0060]

[0061] From Table 1 and Figure 2 The results show that the filler products of Examples 1-3 of the present invention degrade significantly slower than those of Comparative Examples 1-4. The filler products of Examples 1-3 were essentially completely degraded after 18 months, while the products of Comparative Examples 1-4 began to degrade completely after 12 months and were essentially completely degraded after 15 months. These results indicate that the filler products of Examples 1-3 of the present invention can achieve the goal of faster onset of action and longer duration of action.

[0062] Experiment 2: Skin Irritation Test

[0063] Twenty-one SPF-grade Wi Star rats, 6 weeks old and weighing 200±20g, were selected, with half males and half females. They were housed separately in cages under room temperature and relative humidity (50±5)%, with 12-hour light-dark cycles, and free access to food and water. The 21 rats were randomly divided into 7 groups of 3 rats each for skin irritation testing.

[0064] Injections were administered at predetermined intervals to the deep subcutaneous tissue on both sides of the rat's back using a multi-point micro-injection method. Specifically, rats in each group were fasted for 12 hours and deprived of water for 4 hours prior to the procedure. Anesthesia was achieved via intraperitoneal injection of 7% chloral hydrate (0.03 mL / kg body weight). After anesthesia, the skin at the injection sites on the rat's back was prepared and routinely disinfected with 75% medical alcohol according to aseptic principles. The products from Example 1 and Comparative Examples 1-4 were injected into each group of rats. The injection sites were spaced 1 cm apart, with a dose of 10 μL per site, for a total injection of 0.2 ml. Gentle massage was performed after injection, and the rats were observed for 48 hours post-injection. The results are shown in Table 2.

[0065] Table 2 Skin reaction of mice in each group

[0066]

[0067] As can be seen from the results in Table 2, the products of Examples 1-3 and Comparative Examples 1-4 of the present invention have no obvious irritant effect on rats.

[0068] Experiment 3: Clinical improvement in wrinkles

[0069] Fifteen healthy volunteers, aged 35-45 years, were selected as the experimental subjects, including 5 males and 10 females. All volunteers were randomly divided into 5 groups of 3 volunteers each. The effects of the composite cosmetic filler compositions of Example 1 and Comparative Examples 1-4 on human skin wrinkles under experimental conditions were investigated. The cosmetic filler compositions of Example 1 and Comparative Examples 1-4 were injected into the periorbital skin of each group of volunteers. The specific injection method was as follows: the injection volume was 50 μL each time, the injection point spacing was 1 cm, and the total injection volume was 2 mL. The improvement of wrinkles at the injection site before injection, 2 days after injection, and 7 days after injection were recorded, and the results were averaged. The wrinkle score ranged from 1 to 10, with 10 being the highest wrinkle level and 1 being the lowest wrinkle level (no wrinkles). This score was given by a professional cosmetic physician. During the experiment, the volunteers in each group maintained basically the same diet and lifestyle. The results are shown in Table 3.

[0070] Table 3. Wrinkle improvement in each group of volunteers.

[0071]

[0072]

[0073] As shown in Table 3, after injection of the composite cosmetic filler compositions of Example 1 and Comparative Examples 1-4, the wrinkles at the injection sites of all groups of volunteers were significantly reduced; however, compared with the products of Comparative Examples 1-4, the wrinkle improvement was significantly better after injection using the filler of Example 1 of this invention. These results indicate that the composite cosmetic filler composition prepared in Example 1 of this invention has the effect of reducing wrinkles, while also softening the skin, revitalizing it, and maintaining a youthful appearance.

[0074] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the methods and techniques disclosed above without departing from the scope of the present invention to create equivalent embodiments. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A composite aesthetic filler comprising a decellularized placental extract, characterized in that, The raw materials, by weight, include: 0.1-0.5 parts of decellularized placental extract, 0.05-0.1 parts of calcium alginate, 0.01-0.05 parts of mucopeptide, and 1-3 parts of hydrogel matrix material; The method for preparing the hydrogel matrix material includes: Carboxymethyl cellulose calcium and hyaluronic acid were dissolved in water at a mass ratio of 1~2:5~10:100 to obtain a mixed solution of carboxymethyl cellulose calcium / hyaluronic acid. The bifunctional coupling compound and silver nitrate were dissolved in a 60-80% volume fraction organic alcohol solution at a mass ratio of 1:0.01 to 0.05:100 and then sonicated to obtain a mixed solution of silver ion-modified bifunctional coupling compound. N-vinyl functional monomers and initiators were added to the obtained carboxymethyl cellulose calcium / hyaluronic acid mixed solution to carry out polymerization reaction. After the reaction was completed, a mixed solution of silver ion modified bifunctional coupling compound was added to the obtained product at a volume ratio of 1:0.1~0.

3. The mixture was stirred continuously at 40~60℃ for 2~4h, then allowed to stand for 8~12h, and finally filtered. The obtained gel was washed and dried to obtain hydrogel matrix material. The main active substance in the decellularized placental extract is human placental collagen.

2. The composite cosmetic filler containing decellularized placental extract according to claim 1, characterized in that, The raw materials, by weight, include: 0.1-0.5 parts of decellularized placental extract, 0.05-0.1 parts of calcium alginate, 0.01-0.05 parts of spirulina mucin peptide, and 1-3 parts of hydrogel matrix material.

3. The composite cosmetic filler containing decellularized placental extract according to claim 1, characterized in that, The raw materials, by weight, include: 0.1-0.5 parts of decellularized placental extract, 0.05-0.1 parts of calcium alginate, 0.01-0.05 parts of snail mucus peptide, and 1-3 parts of hydrogel matrix material.

4. The composite cosmetic filler containing decellularized placental extract according to claim 1, characterized in that, The bifunctional coupling compound is selected from any one or a mixture of two or more of bis(succinimide) octanoate, bis(succinimide) adipate, and bis(succinimide) succinate.

5. The composite cosmetic filler containing decellularized placental extract according to claim 1, characterized in that, The organic alcohol is selected from any one of ethanol, propanol, and propylene glycol.

6. The composite cosmetic filler containing decellularized placental extract according to claim 1, characterized in that, The ultrasonic conditions are: power 600~800W, time 30~60min.

7. The composite cosmetic filler containing decellularized placental extract according to claim 1, characterized in that, The functional monomer is selected from any one of N-vinylcaprolactam, N-vinylimidazol, and vinylpyrrolidone; The amount of the functional monomer added is 1 to 3 times the mass of hyaluronic acid.

8. The composite cosmetic filler containing decellularized placental extract according to claim 1, characterized in that, The initiator is selected from any one of ammonium persulfate, potassium persulfate, and sodium persulfate; The amount of the initiator added is 0.3 to 0.5% of the mass of the functional monomer.

9. The composite cosmetic filler containing decellularized placental extract according to any one of claims 1 to 8, characterized in that, The composite cosmetic filler also contains physiological saline, with the saline content being 80-120 parts by weight.

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