A sustained-release composition based on a composite aqueous phase gel network and a preparation method and application thereof

Abstract

The application discloses a sustained-release composition based on a composite aqueous phase gel network and a preparation method and application thereof, and belongs to the technical field of biological industry. The composition comprises an aqueous phase gel network forming agent, papain and oil beads; the aqueous phase gel network forming agent comprises carbomer, xanthan gum and acryloyldimethylammonium tosylate / behenyl alcohol polyether-25 methacrylate crosslinking polymer. The application forms a compact three-dimensional space structure through the synergistic effect of three gelling agents, simultaneously realizes the stable suspension of the oil beads, the activity protection of the papain and the stimulation reduction, and effectively solves the problems of poor stability, great stimulation and poor compatibility with a skin repair biological product matrix of the papain in the prior art. The preparation process of the application is simple, has good industrialization prospect, the obtained composition has high stability, is mild and non-irritating, and is suitable for sensitive skin.

Description

Technical Field

[0001] This invention belongs to the field of biotechnology, specifically relating to a sustained-release composition based on a composite aqueous colloidal network, its preparation method and application, and is particularly suitable for bioactive preparations containing enzyme-based active ingredients. Background Technology

[0002] Papain is a thiol protease derived from papaya fruit and belongs to the category of active protein components in the field of biological enzyme preparations. In the biopharmaceutical and biomanufacturing industries, the stability protection and controlled release of enzyme active ingredients are key technical challenges. In cosmetic applications, papain, due to its ability to gently exfoliate and promote skin metabolism, has been widely used in cosmetics with exfoliating, whitening, and skin-improving effects. However, the application of papain in the cosmetic field has long faced two major technical challenges: first, the enzyme activity is easily deactivated by factors such as temperature, pH, metal ions, and oxidation, leading to a decrease in product efficacy during storage; second, high concentrations of papain, when directly applied to the skin, may cause irritating and uncomfortable reactions such as stinging, burning, and redness, particularly limiting its use in people with sensitive skin.

[0003] To address the stability issue of papain, existing technologies typically employ encapsulation techniques to physically isolate the papain, thereby improving its stability. Chinese patent application CN116549365A discloses a natural active composition for inhibiting protease activity, using natural ingredients such as witch hazel extract and soapberry extract to suppress protease activity. Chinese patent application CN118001189 discloses a stable suspended oil droplet composition, using polyethylene glycol-75 in combination with an acrylate / C10-30 alkanol acrylate crosspolymer to stabilize the oil droplets. This involves using thickeners such as acrylate / C10-30 alkanol acrylate crosspolymers to stabilize suspended oil droplets. For sustained-release applications, existing technologies often employ microencapsulation and lyophilized powder. Other methods include encapsulating papain in polyacrylamide gels to prepare biofilm materials for use in skin whitening products; and immobilizing papain using various methods such as cryo-gel encapsulation, modified encapsulation, and UV-initiated in-situ polymerization encapsulation. However, these technologies often suffer from problems such as complex preparation processes, high costs, or poor compatibility with cosmetic matrices. In the field of aqueous colloidal network technology, acrylate / C10-30 alkanol acrylate crosspolymers, due to their unique molecular structure, can form stable three-dimensional networks with excellent thickening and suspending abilities. Nanocellulose and hyaluronic acid self-assembled colloidal particles can also construct stable network structures. However, current technologies have not yet organically combined aqueous colloidal network oil droplet stabilization technology with papain sustained-release technology to form a synergistic system that can both stabilize oil droplets and achieve enzyme sustained release.

[0004] However, existing technologies still have the following significant drawbacks: 1) Poor stability and easy inactivation of enzyme activity: When free papain is directly added to the aqueous phase of cosmetics, it is highly susceptible to temperature fluctuations, pH changes, metal ions (such as copper and iron ions), and oxidation, leading to enzyme denaturation and inactivation. 2) Strong immediate irritation: High concentrations of free enzymes, when applied directly to the skin, especially thin or damaged skin, may cause discomfort such as stinging, burning, and redness. 3) Poor compatibility between sustained-release technology and formulation matrix: Existing sustained-release carriers such as microcapsules and lyophilized powders (e.g., polyacrylamide gels, chitosan microspheres) often have poor compatibility with the emulsification systems of cosmetic creams and serums, easily leading to uneven product texture, roughness, or a grainy feel. 4) Lack of a synergistic stabilization system: Existing technologies are mostly "single-point solutions"—either focusing only on the stabilization and encapsulation of the enzyme or only on the suspension and stabilization of oil droplets. A unified and synergistic system that integrates oil phase stabilization, enzyme activity protection, and irritation-prone sustained release has not been constructed.

[0005] In summary, existing technologies fail to provide a simple, stable, and skin-friendly solution that simultaneously addresses the three interrelated problems of poor papain stability, high irritation, and poor compatibility with oil-phase systems. Therefore, developing a composition and its preparation method that can synergistically achieve stable oil droplet suspension, papain activity protection, and sustained-release of irritants through a single system is of great significance for developing highly effective, gentle, and stable enzyme-containing cosmetics. Summary of the Invention

[0006] In view of the technical problems of poor stability and high irritation of papain in cosmetic applications in the prior art, and the lack of a composite aqueous colloidal network system that can simultaneously achieve oil phase stability, enzyme activity protection and irritation-resistant sustained release, the present invention aims to provide a sustained-release composition based on a composite aqueous colloidal network, its preparation method and application.

[0007] To achieve the above objectives, the present invention employs the following technical solution: In a first aspect, the present invention provides a sustained-release composition based on a composite aqueous colloidal network, comprising an aqueous colloidal network forming agent, papain, and oil droplets; The aqueous colloidal network forming agent comprises carbomer, xanthan gum, and ammonium acryloyldimethyl taurate / behenol polyether-25 methacrylate crosspolymer.

[0008] The carbomer is carbomer 980; and in the composition, carbomer 980 is 0.001-10.0 parts; xanthan gum is 0.001-10.0 parts; and acryloyldimethyl taurate ammonium / behenol polyether-25 methacrylate crosspolymer is 0.001-10.0 parts.

[0009] Carbomer 980, as an anionic thickener, can form a denser composite network structure with the rigid double helix structure of xanthan gum and the hydrophobic associative crosslinking network of BLV. Within this particulate range, the three components synergistically exert optimal steric hindrance and viscoelasticity. This limited particulate range ensures an optimal balance between stability, sustained release, and skin feel in the composite colloidal network.

[0010] The oil droplets are oil droplets containing fat-soluble active ingredients prepared using microfluidic technology.

[0011] Microfluidic technology enables the production of oil droplets with uniform particle size (typically tens to hundreds of micrometers), ensuring accurate dosage and consistent skin feel with each application. Simultaneously, these oil droplets encapsulate lipid-soluble active ingredients, physically isolating them from water, oxygen, and other incompatible components in the formulation, significantly improving the long-term stability of sensitive active ingredients. The small and uniform particle size facilitates even spread on the skin, fusing with the sebum film through the principle of "like dissolves like," promoting targeted release of active ingredients and penetration into the stratum corneum, thus enhancing bioavailability. Furthermore, these oil droplets achieve a "water-like" skin feel, avoiding the heavy, greasy feeling of traditional oil-based formulations.

[0012] The composition also contains a humectant and / or a chelating agent.

[0013] Preferably, the humectant comprises at least one of glycerin, 1,2-pentanediol, and 1,2-hexanediol; and the chelating agent comprises disodium EDTA.

[0014] The addition of moisturizers enhances the hydration of the stratum corneum, softening the skin and preventing dryness and cracking. Simultaneously, it works synergistically with the complex colloidal network to further improve the product's moisturizing performance. Chelating agents (disodium EDTA) effectively address the issue of papain activity being easily deactivated by metal ions in the formulation by chelating them, providing a purer and more stable microenvironment for enzyme activity.

[0015] It also contains at least one of the following active ingredients: mitochondrial energy globulin, recombinant type III collagen, sodium DNA, carnosine, serum protein, fibronectin, and elastin.

[0016] Secondly, the present invention provides a method for preparing the sustained-release composition based on a composite aqueous colloidal network, comprising the following steps: Carbomer, xanthan gum, and ammonium acryloyl dimethyl taurate / behenol polyether-25 methacrylate crosspolymer were dispersed in an aqueous phase to form a composite aqueous colloidal network. Papain and oil droplets were added to the composite aqueous colloidal network and mixed evenly to obtain the sustained-release composition.

[0017] The step of dispersing carbomer, xanthan gum, and ammonium acryloyldimethyl taurate / behenol polyether-25 methacrylate crosspolymer in an aqueous phase specifically includes: Purified water and a chelating agent are mixed and heated to form phase A; The humectant is mixed and dispersed with the carbomer, xanthan gum and ammonium acryloyl dimethyl taurate / behenol polyether-25 methacrylate crosspolymer, and then added to phase A.

[0018] The chelating agent, pre-mixed with purified water under heating conditions, can fully chelate metal ions in the water, providing a pure microenvironment for the subsequently added enzyme active ingredients. The humectant and gelling agent are pre-mixed and dispersed, which helps the gelling agent to be evenly dispersed when added to phase A, avoiding local agglomeration. Heating to 80 ℃~85 ℃ can promote the full hydration and swelling of the gelling agent, forming a denser three-dimensional network structure, laying the foundation for the stable encapsulation of the subsequent active ingredients.

[0019] The step of adding papain and oil droplets to the composite aqueous colloidal network specifically includes: The mixed phase obtained by mixing phase A with the carbomer, xanthan gum, and ammonium acryloyldimethyl taurate / behenol polyether-25 methacrylate crosspolymer was cooled to 40 ℃~45 ℃; then the papain and oil droplets were added. This ensured the integrity and activity retention of the temperature-sensitive active ingredients during processing.

[0020] It also includes one or more active ingredients selected from the following: mitochondrial energy globulin, recombinant type III collagen, sodium DNA, carnosine, serum protein, fibronectin, and elastin.

[0021] The active ingredients, along with papain and oil droplets, are added after cooling to avoid the damage of peptides and proteins caused by high temperatures. The addition of multiple active ingredients gives the final composition multiple skincare benefits, including nourishing, repairing, moisturizing, anti-wrinkle, firming, and soothing. These benefits synergistically enhance the exfoliating effect of papain and the barrier-repairing effect of the oil droplets, achieving a complete skincare cycle of "cleansing-repairing-anti-aging." Simultaneously, the complex aqueous colloidal network stably encapsulates these water-soluble active ingredients, preventing degradation or inactivation and ensuring the product's efficacy stability during storage.

[0022] Thirdly, the present invention provides the use of the sustained-release composition based on the composite aqueous colloidal network in the preparation of skin repair bioproducts for skin repair and / or anti-aging.

[0023] Compared with the prior art, the present invention achieves the following technical effects: The sustained-release composition based on a composite aqueous colloidal network provided by this invention comprises an aqueous colloidal network forming agent composed of carbomer, xanthan gum, and behenyl dimethyl taurate / 25 methacrylate crosspolymer (BLV), papain, and oil droplets. Through the synergistic effect of the three gelling agents, a dense three-dimensional structure is formed. This structure, on the one hand, physically protects papain from the effects of moisture, oxygen, and metal ions, significantly prolonging its activity retention rate; on the other hand, it utilizes high viscoelasticity to firmly suspend the oil droplets, preventing them from agglomerating or floating. Simultaneously, this three-dimensional network achieves sustained release by limiting the diffusion rate of papain, avoiding irritation caused by instantaneous contact of high-concentration enzymes with the skin. This achieves a synergistic balance between oil droplet stability, enzyme activity protection, and irritation-free sustained release, solving the technical problem of the inability to simultaneously achieve these three objectives in existing technologies.

[0024] The method for preparing the composition provided by this invention involves first dispersing three gelling agents in an aqueous phase to form a composite aqueous colloidal network, and then adding papain and oil droplets to this network and mixing them evenly. The three gelling agents can be fully hydrated and dispersed under heating conditions, forming a uniform and dense three-dimensional network structure. Papain and oil droplets are added after the colloidal network has formed, avoiding the damage to enzyme activity caused by high temperatures and the risk of oil droplet rupture at high temperatures. The active ingredient is uniformly embedded in the formed network structure, ensuring its stable dispersion and sustained-release effect in the product. This method is based on conventional cosmetic heating, stirring, and cooling feeding processes, requiring no complex or expensive special equipment, and has good feasibility for industrial implementation.

[0025] This invention, through experiments, found that the composite aqueous colloidal network formed by the combination of carbomer 980, xanthan gum, and BLV exhibits significantly better performance than single gelling agents (Comparative Example 2) or combinations of two (Comparative Example 3) in terms of stable oil droplet suspension, protection of papain activity, and sustained-release reduction of irritation. Cold and heat cycling and long-term stability tests (Tables 1-2) showed that Comparative Example 2, containing only carbomer 980, showed oil droplet floating after 3 months, while Examples 1-3 remained uniformly stable for 6 months. Irritation assessment (Table 3) showed that the skin soothing improvement rate of Comparative Example 2 was only 68.93%, far lower than the 98.21% of Example 1. Efficacy tests (Tables 4-6) also confirmed that the stratum corneum moisture content, TEWL, and skin luster of Comparative Example 2 showed a deteriorating trend after 14 days, while Examples 1-3 showed continuous improvement. The above results confirm that the three gelling agents produced a synergistic effect, constructing a composite network structure that can both stabilize suspended oil droplets (micrometer scale) and effectively limit papain diffusion, achieving sustained-release protection (submicrometer scale). This structure cannot be achieved by single or two-component colloids, thus simultaneously solving the two major technical challenges of activity protection and physical suspension.

[0026] The application provided by this invention utilizes a composite aqueous colloidal network to achieve a sustained release of papain, allowing for gentle and continuous exfoliation. This avoids the immediate irritation issues associated with traditional high-concentration enzyme preparations, making it safe for sensitive skin. The lipid-soluble active ingredients (such as ceramides, squalane, and chamomile extract) encapsulated in oil droplets are released upon application, providing barrier repair and anti-aging benefits. Combined with the deep repair and regeneration effects of various peptide and protein active ingredients, these three components synergistically achieve a combined effect of gentle exfoliation, barrier repair, and anti-aging. This application extends the technical solution of this invention from the composition itself to the field of end products, possessing broad industrial application prospects and market value. Attached Figure Description

[0027] Figure 1 This refers to the average change in the moisture content of the stratum corneum of the skin at different time points in Example 1 of the present invention. Figure 2 This refers to the average change in the moisture content of the stratum corneum of the skin at different time points in Example 2 of the present invention. Figure 3 This is the average change in the moisture content of the stratum corneum of the skin at different time points in Comparative Example 1 of the present invention; Figure 4 This is the average change in the moisture content of the stratum corneum of the skin at different time points in Comparative Example 2 of the present invention; Figure 5 This is the average change in the moisture content of the stratum corneum of the skin at different time points in Comparative Example 3 of the present invention; Figure 6 This refers to the average change of TEWL values ​​at different time points in Embodiment 1 of the present invention. Figure 7 This refers to the average change of TEWL values ​​at different time points in Example 2 of the present invention. Figure 8 This is the variation of the average TEWL value at different time points in Comparative Example 1 of the present invention; Figure 9 This is the variation of the average TEWL value at different time points in Comparative Example 2 of the present invention; Figure 10 This is the variation of the average TEWL value at different time points in Comparative Example 3 of the present invention; Figure 11 The results of skin gloss testing after using the composition of Example 1 of the present invention; Figure 12 The results of skin gloss testing after using the composition of Example 2 of the present invention; Figure 13 The results of skin gloss testing after using the composition of Comparative Example 1 of the present invention; Figure 14 The results of skin gloss testing after using the composition of Comparative Example 2 of the present invention; Figure 15 The results of skin gloss testing after using the composition of Comparative Example 3 of the present invention; Figure 16 Radar charts comparing the skin feel of the compositions of Examples 1, 2, and Comparative Examples 1-3 in terms of touch, stickiness, and absorption speed. Detailed Implementation

[0028] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0029] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0030] The "composite aqueous colloidal network" described in this invention refers to a three-dimensional spatial network structure synergistically formed in an aqueous phase by three gelling agents: carbomer 980, xanthan gum, and ammonium acryloyl dimethyl taurate / behenol polyether-25 methacrylate crosslinked polymer (BLV), through physical and / or chemical crosslinking. This network has the following characteristics: first, it possesses a dense mesh structure, capable of physically isolating active ingredients from adverse external factors; second, it exhibits suitable viscoelasticity, capable of stably suspending oil droplets and other particulate components; and third, it possesses shear-thinning rheological properties, facilitating product application.

[0031] Carbomer 980 is a high molecular weight crosslinked acrylic polymer and belongs to the anionic thickener category. Its thickening mechanism lies in the neutralization of carboxyl groups on the polymer molecular chains by a neutralizing agent, forming negative charges. Due to electrostatic repulsion, the molecular chains extend from a coiled state to a stretched state, forming a three-dimensional network structure, thereby achieving thickening and suspending functions. In this invention, Carbomer 980 is used directly without the need for additional neutralizing agents.

[0032] Xanthan gum is a natural high-molecular-weight polysaccharide produced by the fermentation of Xanthomonas auricula-judae. Its thickening mechanism is as follows: the main molecular chain is similar to cellulose, and the side chains carry negative charges, forming a stable rigid double helix structure in aqueous solution. Multiple double helix structures are bonded together by intermolecular forces to form a three-dimensional network structure that runs through the entire solution, thereby restricting the flow of water molecules and increasing the viscosity of the system.

[0033] Acryloyldimethyl taurate ammonium / behenol polyether-25 methacrylate crosspolymer (BLV) is a hydrophobically modified cross-linked polyelectrolyte. Its molecular backbone is a permanently negatively charged polyelectrolyte (acryloyldimethyl taurate), with long-chain hydrophobic groups (behenol polyether-25) linked to its side chains. This product is pre-neutralized and requires no additional pH adjustment. Its thickening mechanism is as follows: the hydrophilic backbone rapidly hydrates, and the negatively charged sulfonate groups generate electrostatic repulsion, causing the cross-linked polymer particles to absorb water and swell; simultaneously, the hydrophobic side chains aggregate to form hydrophobic association regions (physical cross-linking points), significantly strengthening and expanding the three-dimensional network, ultimately forming a stable three-dimensional network structure supported by both covalent cross-linking points and dynamic physical association points.

[0034] The "oil droplets" described in this invention refer to spherical oily microparticles with a uniform particle size (typically tens to hundreds of micrometers) prepared using microfluidic technology. Microfluidic technology, by precisely controlling the flow rate ratio of the oil phase and the aqueous phase in microchannels, can produce oil droplets with uniform particle size and controllable structure. These oil droplets can have a pure oil core structure or a more complex core-shell structure. The oil droplets of this invention encapsulate lipid-soluble active ingredients (such as chamomile extract, paulownia bark extract, ceramides, etc.) internally, and are stably suspended externally by an aqueous colloidal network. Its core function is to achieve precise encapsulation, synergistic enhancement, and efficient transdermal delivery of multiple highly active and effective ingredients through advanced carrier technology, thereby providing a highly efficient, stable, and skin-feeling repair and anti-aging solution. Microfluidic technology can precisely manufacture oil droplets with a uniform particle size (typically tens to hundreds of micrometers), ensuring accurate dosage and consistent skin feel with each use. The structure can be a pure oil core or a more complex core-shell structure to protect sensitive ingredients; encapsulating lipid-soluble active ingredients (such as pterostilbene and ceramides) and oils within microbeads physically isolates water, oxygen, and other potentially incompatible ingredients in the formula, greatly improving the long-term stability of active ingredients (especially easily oxidized and deactivated Pterocarpus marsupium bark extract); the small and uniform particle size helps to spread evenly on the skin, and through the principle of like dissolves like, it is easier to integrate with the sebum film, promoting the targeted release of encapsulated active ingredients and penetration into the stratum corneum, improving bioavailability; transforming high-concentration nourishing oils into refreshing "oil beads," which are released by breaking during massage, achieving a "oil-to-water" skin feel, avoiding the heavy and greasy feeling of traditional oil-phase formulas.

[0035] The "lipid-soluble active ingredients" described in this invention refer to active ingredients that can dissolve in oils and have skin-care effects. These include, but are not limited to, plant extracts (such as chamomile extract and paulownia bark extract), ceramides, squalane, jojoba seed oil, and meadowfoam seed oil. These ingredients typically have barrier repair, anti-aging, and moisturizing effects, but due to their lipid-soluble properties, they are difficult to disperse stably and directly in aqueous systems and require stable encapsulation using oil droplet carriers or colloidal networks.

[0036] Papain is a thiol protease extracted from the fruit, stems, and leaves of the papaya (Carica papaya). Its active center contains an essential thiol group (-SH), which can specifically cleave the carboxyl terminus of basic amino acids such as arginine and lysine in peptide chains, catalyzing the hydrolysis of peptide bonds in proteins. In cosmetic applications, papain hydrolyzes aged and accumulated keratin proteins in the stratum corneum, loosening and breaking down the connections between dead skin cells, thereby achieving gentle exfoliation, brightening skin tone, and improving skin texture.

[0037] The "slow release" described in this invention refers to the process of slowly releasing the active ingredient (especially papain) from a complex aqueous colloidal network at a controlled rate. This process is achieved through the following mechanisms: first, the steric hindrance of the three-dimensional network structure restricts the free diffusion of enzyme molecules; second, the physical interactions between the network and enzyme molecules (such as hydrogen bonds and hydrophobic interactions) slow down the enzyme release rate. Through slow release, the irritation caused by instantaneous, direct contact of high-concentration enzymes with the skin is avoided, while simultaneously prolonging the enzyme's action time.

[0038] "Shear thinning" refers to a rheological property of non-Newtonian fluids: at low shear rates (e.g., in a static state), the system exhibits high viscosity, which can stably suspend particulate components; at high shear rates (e.g., during application), the system viscosity rapidly decreases, becoming smooth and easy to spread, facilitating even application of the product to the skin. The composite aqueous colloidal network of this invention exhibits typical shear thinning characteristics, ensuring an ideal user experience during both storage and application.

[0039] Transepidermal water loss (TEWL) refers to the water flux that diffuses through the stratum corneum of the skin to the external environment, measured in g / h / m². TEWL is an important indicator for evaluating skin barrier function: a lower TEWL value indicates a more robust skin barrier function; a higher TEWL value indicates a damaged skin barrier and increased water loss.

[0040] The raw materials used in the examples were sourced as follows: Carbomer 980 was purchased from Lubrizol (CARBOPOL® 980 Polymer); Xanthan gum was purchased from Cosphatec (Cosphaderm® X 34); Acryloyldimethyl taurate / behenol polyether-25 methacrylate crosspolymer (BLV) was purchased from Clariant (Aristoflex BLV); Papain was purchased from Zhuhai Aoyuan Biotechnology Co., Ltd. (Papain); and Oil beads (prepared using microfluidic technology, containing chrysanthemum extract, tung oil bark extract, ceramide, squalane, jojoba seed oil, and meadowfoam seed oil) were purchased from Chongqing Xiaowan Biotechnology Co., Ltd. (Oiltes). TTT-AZ(BH)03; Mitochondrial energy globulin (water, 1,2-pentanediol, 1,2-hexanediol, decapeptide-4) was purchased from Future Polypeptide Biotechnology (Yantai) Co., Ltd., product model: Taishu® Mitochondrial Energy Globule; Recombinant Type III Collagen (Z) was purchased from Baihong Synthetic Biotechnology (Yantai) Co., Ltd., product model: Recombinant Type III Collagen (Z); HYPDRN-Z (sodium DNA, also known as PDRN) was purchased from Baihong Synthetic Biotechnology (Yantai) Co., Ltd., product model: HYPDRN-Z; Other functional ingredients (carnosine, serum protein, fibronectin, elastin) were all commercially available cosmetic grade ingredients; Preservative (phenoxyethanol): purchased from ASHLAND, product model: PE 9010; Chelating agent (disodium EDTA) was purchased from Shijiazhuang Jack Chemical Co., Ltd., product model: disodium ethylenediaminetetraacetate.

[0041] Unless otherwise specified, all experimental materials used in this invention are commercially available products well known to those skilled in the art.

[0042] I. Specific Examples of Sustained-Release Compositions Based on Composite Aqueous Colloidal Networks Example 1 This embodiment provides a sustained-release composition based on a composite aqueous colloidal network, the specific composition and preparation method of which are as follows: (1) Composition formulation (by weight) Purified water to 100 parts, glycerol 5.0 parts, 1,2-pentanediol 3.0 parts, 1,2-hexanediol 2.0 parts, carbomer 980 0.5 parts, xanthan gum 0.3 parts, BLV 0.4 parts, papain 2.0 parts, oil droplets 15.0 parts, mitochondrial energy globulin 5.0 parts, recombinant type III collagen (Z) 3.0 parts, HYPDRN-Z (PDRN) 2.0 parts, carnosine 0.5 parts, serum albumin 0.5 parts, fibronectin 0.3 parts, elastin 0.3 parts, phenoxyethanol 0.5 parts, disodium EDTA 0.05 parts.

[0043] (2) Preparation method Step 1: Weigh out each ingredient according to the above formula.

[0044] Step 2: Add purified water and disodium EDTA to the reaction vessel in sequence, stir evenly, heat to 80-85℃, keep warm and stir until completely dissolved to form phase A.

[0045] Step 3: Mix and disperse glycerol, 1,2-pentanediol, 1,2-hexanediol, carbomer 980, xanthan gum and BLV evenly, slowly add to phase A, and continue stirring until completely dispersed to form a mixed phase AB.

[0046] Step 4: Cool the AB mixed phase to 40-45℃, and add mitochondrial energy globulin, papain, oil droplets, recombinant type III collagen (Z), HYPDRN-Z (PDRN), carnosine, serum albumin, fibronectin, elastin and phenoxyethanol in sequence. Stir for 30 min until homogeneous to obtain the sustained-release composition based on the composite aqueous colloidal network.

[0047] Example 2 This embodiment, based on Example 1, provides a sustained-release composition based on a composite aqueous colloidal network, the specific composition and preparation method of which are as follows: (1) Composition formulation (by weight) The purified water is adjusted to 100 parts, glycerol 8.0 parts, 1,2-pentanediol 2.0 parts, 1,2-hexanediol 2.0 parts, carbomer 980 0.3 parts, xanthan gum 0.5 parts, BLV 0.3 parts, papain 1.0 part, oil droplets 10.0 parts, mitochondrial energy globulin 3.0 parts, recombinant type III collagen (Z) 2.0 parts, HYPDRN-Z (PDRN) 1.5 parts, carnosine 0.3 parts, serum albumin 0.3 parts, fibronectin 0.2 parts, elastin 0.2 parts, phenoxyethanol 0.5 parts, and disodium EDTA 0.03 parts.

[0048] (2) The preparation method is the same as in Example 1.

[0049] Example 3 This embodiment, based on Example 1, provides a sustained-release composition based on a composite aqueous colloidal network, the specific composition and preparation method of which are as follows: (1) Composition formulation (by weight) Purified water to 100 parts, glycerol 10.0 parts, 1,2-pentanediol 4.0 parts, 1,2-hexanediol 3.0 parts, carbomer 980 0.8 parts, xanthan gum 0.2 parts, BLV 0.6 parts, papain 3.0 parts, oil droplets 20.0 parts, mitochondrial energy globulin 8.0 parts, recombinant type III collagen (Z) 5.0 parts, HYPDRN-Z (PDRN) 4.0 parts, carnosine 0.8 parts, serum albumin 0.8 parts, fibronectin 0.5 parts, elastin 0.5 parts, phenoxyethanol 0.8 parts, disodium EDTA 0.08 parts.

[0050] (2) The preparation method is the same as in Example 1.

[0051] Example 4 This embodiment, based on Example 1, provides a sustained-release composition based on a composite aqueous colloidal network, the specific composition and preparation method of which are as follows: (1) Composition formulation (by weight) Purified water to 100 parts, glycerol 5.0 parts, 1,2-pentanediol 3.0 parts, 1,2-hexanediol 2.0 parts, carbomer 980 0.005 parts, xanthan gum 0.005 parts, BLV 0.005 parts, papain 2.0 parts, oil droplets 15.0 parts, mitochondrial energy globulin 5.0 parts, recombinant type III collagen (Z) 3.0 parts, HYPDRN-Z (PDRN) 2.0 parts, carnosine 0.5 parts, serum albumin 0.5 parts, fibronectin 0.3 parts, elastin 0.3 parts, phenoxyethanol 0.5 parts, disodium EDTA 0.05 parts.

[0052] (2) Preparation method The procedure is the same as steps 2-4 in Example 1. The resulting composition appears as a translucent gel with oil droplets uniformly suspended without aggregation or stratification. After a thermal cycling test (24 hours each at -20°C and 50°C, for 6 cycles), the oil droplets remained uniformly suspended without floating or aggregation. The viscosity at 25°C was measured to be 450 mPa·s using a viscometer (Brookfield, rotor S63, 10 rpm), indicating the formation of an effective colloidal network.

[0053] Example 5 This embodiment, based on Example 1, provides a sustained-release composition based on a composite aqueous colloidal network, the specific composition and preparation method of which are as follows: (1) Composition formulation (by weight) Purified water to 100 parts, glycerol 5.0 parts, 1,2-pentanediol 3.0 parts, 1,2-hexanediol 2.0 parts, carbomer 980 8.0 parts, xanthan gum 6.0 parts, BLV 7.0 parts, papain 2.0 parts, oil droplets 15.0 parts, mitochondrial energy globulin 5.0 parts, recombinant type III collagen (Z) 3.0 parts, HYPDRN-Z (PDRN) 2.0 parts, carnosine 0.5 parts, serum albumin 0.5 parts, fibronectin 0.3 parts, elastin 0.3 parts, phenoxyethanol 0.5 parts, disodium EDTA 0.05 parts.

[0054] (2) Preparation method Steps 1-2 are the same as in Example 1. In Step 3, the humectant is mixed with the three gelling agents and then slowly added to Phase A. The stirring time needs to be appropriately extended to 60 minutes to ensure complete dispersion. In Step 4, the active ingredients are added after cooling. The resulting composition appears as a milky white, thick gel with stable oil droplets suspended in the air. After 6 cycles of hot and cold cycling (as above), the oil droplets did not float or aggregate. The viscosity at 25°C is 12800 mPa·s, still exhibiting good spreadability, and the papain activity retention rate (determined by the Folin-phenol method) is 92%, comparable to 94%-96% in Examples 1-3, indicating that the colloidal network did not adversely inhibit enzyme activity within this high content range.

[0055] Comparative Example 1 (without composite colloidal network) Comparative Example 1: Based on Example 1, this example provides a sustained-release composition (excluding the composite colloidal network) based on a composite aqueous colloidal network. The specific composition and preparation method are as follows: (1) Composition formulation (by weight) It is basically the same as Example 1, except that: Carbomer 980, xanthan gum and BLV are not added (i.e., it does not contain a composite aqueous colloidal network).

[0056] (2) Preparation method Mix purified water, disodium EDTA, glycerol, 1,2-pentanediol, and 1,2-hexanediol and heat to 80-85℃. After cooling to 40-45℃, add the remaining components (papain, oil droplets, etc.) in sequence and stir for 30 minutes until homogeneous.

[0057] Comparative Example 2 (containing only a single gelling agent) Comparative Example 2, based on Example 1, provides a sustained-release composition (containing only a single gelling agent) based on a composite aqueous colloidal network. The specific composition and preparation method are as follows: (1) Composition formulation (by weight) It is basically the same as Example 1, except that only Carbomer 980 (0.5 parts) is added, and xanthan gum and BLV are not added.

[0058] (2) The preparation method is the same as in Example 1.

[0059] Comparative Example 3 (containing only two types of gelling agents, without BLV) Comparative Example 3, based on Example 1, provides a sustained-release composition based on a composite aqueous colloidal network (containing only two gelling agents and no BLV). The specific composition and preparation method are as follows: (1) Composition formulation (by weight) It is basically the same as Example 1, except that only Carbomer 980 (0.5 parts) and Xanthan gum (0.3 parts) are added, and BLV is not added.

[0060] (2) The preparation method is the same as in Example 1.

[0061] Comparative Example 4 (same as Example 1, except without oil droplets) This comparative example provides a sustained-release composition based on a composite aqueous colloidal network (basically the same as in Example 1, except that it does not contain oil droplets). The specific composition and preparation method are as follows: (1) Composition formulation (by weight) It is basically the same as Example 1, except that Comparative Example 4 does not add microfluidic oil control beads.

[0062] (2) The preparation method is the same as in Example 1.

[0063] II. Experimental Study on the Effect of Sustained-Release Composition Based on Composite Aqueous Colloidal Network Example 6: Physical Stability Test The compositions obtained in Examples 1-3 and Comparative Examples 1-3 were used as test samples.

[0064] (1) Hot and cold cycle test Each sample was placed at -20℃ and 50℃ for 24 hours each, constituting one cycle, for a total of 6 cycles. After each cycle, the appearance of the samples was observed, and the changes in oil droplet floating, aggregation, stratification, and texture were recorded. The results are shown in Table 1.

[0065] Table 1: Results of thermal cycling for each sample

[0066] As shown in Table 1, after 6 cycles of hot and cold cycling, no oil droplets floated, aggregated, or stratified, and the texture remained uniform and stable. The test results for Examples 2 and 3 were the same as for Example 1; after each cycle, no oil droplets floated, aggregated, or stratified, and the texture remained uniform. Comparative Example 1 showed oil droplet floating, aggregation, and stratification in the first cycle, which continued until the sixth cycle. Comparative Example 2 showed no oil droplet floating or stratification in 6 cycles, and the texture remained uniform. Comparative Example 3 showed oil droplet floating, aggregation, and stratification in the first cycle, which continued until the sixth cycle. Examples 1-3 remained stable after 6 cycles of hot and cold cycling. Comparative Example 1 (without colloidal network) and Comparative Example 3 (containing only two gelling agents) both showed significant oil droplet floating and stratification. Although Comparative Example 2 (containing only Carbomer 980) showed good stability during hot and cold cycling, subsequent long-term stability tests showed its effect was limited.

[0067] (2) Long-term stability test Based on experiment (1), this experiment placed each sample at room temperature and 50°C for 1 month, 3 months and 6 months respectively, and observed the changes in the appearance of the samples. The results are shown in Table 2.

[0068] Table 2: Long-term stability results of each sample

[0069] As shown in Table 2, Example 1 showed no oil droplet floating, aggregation, or stratification at 1 month, 3 months, and 6 months, exhibiting a uniform and stable texture. The test results for Examples 2 and 3 were the same as for Example 1. Comparative Example 1 showed oil droplet floating, aggregation, and stratification at 1 month, 3 months, and 6 months. Comparative Example 2 showed no oil droplet floating and a uniform texture at 1 month, slight oil droplet floating at 3 months, and significant oil droplet floating and stratification at 6 months. Comparative Example 3 showed oil droplet floating, aggregation, and stratification at 1 month, 3 months, and 6 months. Examples 1-3 remained stable throughout the 6-month long-term storage. Comparative Example 2 showed oil droplet floating after 3 months and significant stratification after 6 months, indicating that Carbomer 980 alone cannot stably suspend oil droplets for a long period. The synergistic effect of the combination of Carbomer 980, xanthan gum, and BLV in Examples 1-3 was significantly better than the suspension effect of any single or paired combination. Comparative Example 4 (without oil droplets) showed a soothing improvement rate of only 19.03% in the irritation assessment (see Table 3), which was much lower than Example 1, indicating that oil droplets are also indispensable for achieving comprehensive effects such as repair, moisturizing, and gloss.

[0070] Example 7: Stimulation Assessment Test This embodiment, based on Examples 1-4, conducts irritation assessment tests on the compositions of Examples 1-2 and Comparative Examples 1-4. Following the inclusion criteria, 33 volunteers with sensitive skin were recruited for evaluation using skin models. Samples were distributed to these models. The products were applied morning and evening. Immediately after application, and after 1 day and 7 days, the improvement in subjective feelings such as redness, dryness, stinging, burning, and tightness was assessed using a questionnaire. Results are expressed as an improvement rate (%), as shown in Table 3.

[0071] Table 3: Irritation Assessment Results of Each Sample

[0072] As shown in Table 3, in Example 1, the improvement effects on skin redness immediately after use, 1 day, and 7 days after use were 89.33%, 90.63%, and 91.24%, respectively; the improvement effects on dryness / stirring / burning / tightness were 92.62%, 96.88%, and 96.97%, respectively; and the overall improvement effects on skin soothing were 93.18%, 96.88%, and 98.21%, respectively. In Example 2, the improvement effects on skin redness immediately after use, 1 day, and 7 days after use were 88.97%, 89.94%, and 89.77%, respectively; the improvement effects on dryness / stirring / burning / tightness were 87.49%, 90.15%, and 89.98%, respectively; and the overall improvement effects on skin soothing were 89.30%, 93.22%, and 95.22%, respectively. Comparative Example 1 showed immediate, 1-day, and 7-day improvements in skin redness of 63.13%, 60.09%, and 57.39%, respectively; improvements in dryness / stirring / burning / tightness of 62.29%, 61.11%, and 57.46%, respectively; and overall skin soothing improvements of 64.23%, 57.56%, and 53.24%, respectively. Comparative Example 2 showed immediate, 1-day, and 7-day improvements in skin redness of 73.45%, 68.23%, and 64.10%, respectively; improvements in dryness / stirring / burning / tightness of 69.35%, 65.14%, and 64.21%, respectively; and overall skin soothing improvements of 69.15%, 66.75%, and 68.93%, respectively. Comparative Example 3 showed improvements in skin redness immediately after use, at 1 day, and at 7 days, at 58.12%, 56.31%, and 53.25%, respectively; improvements in dryness / stirring / burning / tightness at 57.69%, 55.33%, and 53.42%, respectively; and overall skin soothing improvements at 55.80%, 54.39%, and 53.22%, respectively. Comparative Example 4 showed improvements in skin redness immediately after use, at 1 day, and at 7 days, at 21.51%, 20.24%, and 20.96%, respectively; improvements in dryness / stirring / burning / tightness at 20.78%, 21.32%, and 18.99%, respectively; and overall skin soothing improvements at 19.31%, 18.16%, and 19.03%, respectively.

[0073] In summary, Examples 1 and 2 are significantly superior to Comparative Examples 1, 2, 3, and 4 in improving skin redness, dryness, stinging, burning, tightness, and overall skin soothing effects. In particular, Example 1 showed an overall skin soothing improvement of 98.21% after 7 days of use, while Comparative Example 4 only showed an improvement of 19.03% after 7 days. This indicates that the composite aqueous colloidal network and microfluidic oil-control beads of the present invention have a good sustained-release effect on papain, significantly reducing immediate irritation and prolonging the soothing effect.

[0074] Example 6: Efficacy Test Based on Examples 1-4, this embodiment conducts efficacy tests on the compositions of Examples 1-3 and Comparative Examples 1-3 of the present invention, as detailed below: (1) Test of stratum corneum moisture content According to the inclusion criteria, 33 eligible subjects were recruited. They applied the sample twice daily, morning and evening, for 7 and 14 consecutive days. Referring to "T / CAB 0152-2022 Test Methods for Seven Efficacy Items of Cosmetics (Anti-wrinkle, Firming, Moisturizing, Oil Control, Repairing, Nourishing, and Soothing)," the skin moisture content of the stratum corneum on the right cheek was measured using a Corneometer CM 825 probe. Three tests were performed at each test site, and the average value was taken. Data were collected before use (D0), on day 7 (D7), and on day 14 (D14). Results are shown in Table 4. Figures 1 to 5 As shown.

[0075] Table 4: Results of stratum corneum moisture content for each sample

[0076] From Table 4 and Figures 1 to 5 Data shows that the average moisture content of the stratum corneum on the cheeks of subjects in Examples 1 and 2 was significantly different after 7 and 14 days of product use compared to before use (P<0.001), indicating that Examples 1 and 2 promoted the restoration of moisture in skin with damaged barriers. The composite aqueous colloidal network had a sustained-release effect on papain, which could reduce the damage of papain to the skin barrier. Similarly, the average moisture content of the stratum corneum on the cheeks of subjects in Comparative Examples 1 and 3 was significantly different after 7 and 14 days of product use compared to before use. The statistically significant difference (P<0.001) was observed in the continuous decrease in stratum corneum moisture content, indicating that without the sustained release of papain via a complex aqueous colloidal network, papain would excessively exfoliate the stratum corneum, leading to barrier damage. In Comparative Example 2, the average stratum corneum moisture content of the cheeks of the subjects increased after 7 days of use (from 37.84 to 45.51), but decreased back to 43.23 after 14 days of use. This suggests that the sustained-release protective effect of carbomer colloid on papain may gradually weaken with long-term use, leading to an enhanced exfoliation effect of papain on the stratum corneum.

[0077] (2) Skin barrier function (TEWL value) test Referring to "T / ZHCA003-2018 Test Method for the Effects of Cosmetics on Transepidermal Water Loss", the TEWL value on the right cheek was measured using a Tewameter™ Hex skin moisture loss meter. Three tests were conducted at each test site, and the average value was taken. Data were collected before use (D0), 7 days after use (D7), and 14 days after use (D14). Results are shown in Table 5. Figures 6-10 .

[0078] Table 5: TEVL values ​​for each sample

[0079] Note: P<0.05, P<0.01, ns P≥0.05, no significant difference. From Table 5 and Figures 6-10 Data shows that in Examples 1 and 2, the transepidermal water loss rate of the cheek skin of the subjects showed a statistically significant difference after 7 days of product use compared to before use (P<0.05), and a highly statistically significant difference after 14 days of product use compared to before use (P<0.01), indicating that Examples 1 and 2 have a promoting effect on the recovery of transepidermal water loss in skin with damaged barrier function. In Comparative Examples 1 and 3, the transepidermal water loss rate of the cheek skin of the subjects showed a continuous increase in TEWL values ​​after 7 and 14 days of product use (comparative examples...). Comparative Example 1: 23.14→25.63→27.75; Comparative Example 3: 23.11→26.71→29.32), indicating that in compositions that do not form an effective sustained-release network, papain excessively exfoliates the stratum corneum, leading to continuous damage to the skin barrier; In Comparative Example 2, the transepidermal water loss rate of the cheek skin of the subjects decreased after 7 days of use (from 24.14 to 20.51), but rebounded to 26.98 after 14 days of use, indicating that the sustained-release effect of a single colloid on papain diminishes with long-term use.

[0080] (3) Skin gloss test Referring to "T / SHFCA 003-2022 Evaluation Test Method for Claims of Nourishing Efficacy in Cosmetics", the skin glossyness of the right cheek was measured using a Skin-Glossymeter GL 200 probe. Three tests were conducted at each test site, and the average value was taken. Data were collected before use (D0), 7 days after use (D7), and 14 days after use (D14). Specific results are shown in Table 6 and... Figures 11-15 As shown.

[0081] Table 6: Results of Skin Glossiness Changes After Product Use

[0082] From Table 6 and Figures 11-15The data show that the average skin gloss of subjects in Examples 1 and 2 was significantly different from that before use after 7 and 14 days of product use (P<0.001), indicating that Examples 1 and 2 promoted the improvement of skin gloss, and the composite aqueous colloidal network had a sustained-release effect on papain, enabling papain to exert its effect for a long time. The average skin gloss of subjects in Comparative Examples 1 and 3 was significantly different from that before use after 7 and 14 days of product use (P<0.001), and the skin gloss continuously decreased, indicating that without the sustained release of papain by the composite aqueous colloidal network, papain would over-exfoliate the stratum corneum, leading to barrier damage and worsened skin gloss. The skin gloss of subjects in Comparative Example 2 improved after 7 days of use (from 5.56 to 5.96), but fell back to 4.82 after 14 days of use, indicating that the sustained-release protection of papain by a single colloid was insufficient to support long-term efficacy. This indicates that the composite aqueous colloidal network of the present invention enables papain to exert its effects in a sustained and controllable manner, thereby continuously improving skin radiance.

[0083] (4) Skin feel and texture test Ten professional sensory evaluators assessed spreadability, absorption speed, residue, and stickiness using a numerical rating scale (1-10 points). Higher scores indicated a more pronounced sensation. A higher spreadability score indicated better spreadability; a higher absorption speed score indicated faster absorption; a higher residue score indicated a stronger residue; and a higher stickiness score indicated a stickier feel on the skin. The average score for each sample across all dimensions was calculated, and the results are shown in Table 7. Figure 16 As shown.

[0084] Table 7: Average scores given by sensory evaluators for each skin feel dimension

[0085] From Table 7 and Figure 16Data shows that Example 1 scored similarly to Comparative Example 1 (without colloidal network) in terms of spreadability (9.38 points) and absorption speed (9.52 points), both exhibiting excellent smoothness and rapid absorption. However, Example 1 (stickiness 6.67 points) scored slightly higher than Comparative Example 1 (stickiness 4.67 points) in terms of residue and stickiness. This is due to the inherent viscosity and water-retention properties of the composite aqueous colloidal network, which are characteristic texture features of a functional formulation. Compared to Comparative Example 2 (containing only Carbomer 980, stickiness 7.27 points), Example 1 exhibited significantly lower stickiness, indicating that the addition of BLV and xanthan gum improved the viscous feel commonly found in single-carbomer formulations. Overall, Example 1 provides a moderate and non-greasy skin feel while ensuring excellent spreadability and absorption speed, achieving a good balance between efficacy and user comfort. Comparative Example 3 also exhibits good spreadability and absorption rate, but it lacks the network structure integrity brought by BLV, and its long-term stability and sustained-release efficacy are inferior to Example 1.

[0086] The comparative experimental results of the above embodiments and comparative examples show that: First, in terms of stability, the present invention uses a composite aqueous colloidal network formed by combining carbomer 980, xanthan gum, and ammonium acryloyl dimethyl taurate / benzyl alcohol polyether-25 methacrylate cross-linked polymer (BLV), which can stably suspend oil droplets for a long time and maintain uniform texture under cold and hot cycling and long-term storage conditions. This is significantly better than compositions that do not contain a colloidal network, contain only a single gelling agent, or contain only two gelling agents.

[0087] Secondly, in terms of reducing irritation, the composite aqueous colloidal network of this invention has a good sustained-release effect on papain. In the irritation assessments immediately after use, 1 day and 7 days after use, the improvement effect on skin redness, dryness / stirring / burning / tightness and the overall soothing effect are significantly better than those of the respective comparison ratios.

[0088] Third, in terms of efficacy enhancement, the composition of the present invention can significantly increase the moisture content of the stratum corneum, improve the skin barrier function and enhance skin radiance, achieving synergistic effects of gentle exfoliation, barrier repair and anti-aging.

[0089] Fourth, in terms of skin feel, the composition of the present invention has good spreadability, absorption speed and moderate skin feel, providing an excellent user experience.

[0090] In summary, this invention successfully achieves a synergistic balance between stable oil droplet suspension, papain activity protection, and sustained-release of irritant by constructing a composite aqueous colloidal network synergistically formed by carbomer 980, xanthan gum, and BLV. Comparative experimental results show that the combination of these three components is superior to compositions without a colloidal network, containing only a single gelling agent, or containing only two gelling agents in terms of long-term oil droplet suspension stability, sustained-release protection of enzyme activity, and skin barrier repair efficacy, confirming a significant synergistic effect among the three gelling agents. This invention effectively solves the core technical problems of poor papain stability, high irritation, and poor compatibility with skin repair biopharmaceutical matrices in existing technologies, and has good prospects for industrial application. Furthermore, the composite aqueous colloidal network of this invention significantly improves the activity protection rate of papain, and the release rate can be controllably adjusted by regulating the ratio of the three gelling agents, providing a feasible solution for the long-term stable storage of bioactive enzymes under non-refrigerated conditions.

[0091] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A sustained release composition based on a composite aqueous phase gel network, characterized in that, It contains an aqueous colloidal network forming agent, papain, and oil droplets; The aqueous colloidal network forming agent comprises carbomer, xanthan gum, and ammonium acryloyldimethyl taurate / behenol polyether-25 methacrylate crosspolymer.

2. The extended release composition based on composite aqueous phase gel network according to claim 1, characterized in that, The carbomer is carbomer 980; and in the composition, carbomer 980 is 0.001-10.0 parts; xanthan gum is 0.001-10.0 parts; and acryloyldimethyl taurate ammonium / behenol polyether-25 methacrylate crosspolymer is 0.001-10.0 parts.

3. The composite aqueous phase gel network based sustained release composition according to claim 1, wherein, The oil droplets are oil droplets containing fat-soluble active ingredients prepared using microfluidic technology.

4. The composite aqueous phase gel network based sustained release composition as claimed in claim 1 wherein, The composition further comprises a humectant and / or a chelating agent; preferably, the humectant comprises at least one selected from glycerin, 1,2-pentanediol and 1,2-hexanediol; and the chelating agent comprises disodium EDTA.

5. The composite aqueous phase gel network based sustained release composition as claimed in claim 1 wherein, It also contains at least one of the following active ingredients: mitochondrial energy globulin, recombinant type III collagen, sodium DNA, carnosine, serum protein, fibronectin, and elastin.

6. Process for the preparation of the sustained release composition based on composite aqueous phase gel network according to any one of claims 1 to 5, characterized in that, Includes the following steps: Carbomer, xanthan gum, and ammonium acryloyl dimethyl taurate / behenol polyether-25 methacrylate crosspolymer were dispersed in an aqueous phase to form a composite aqueous colloidal network. Papain and oil droplets were added to the composite aqueous colloidal network and mixed evenly to obtain the sustained-release composition.

7. The method for preparing the sustained-release composition based on a composite aqueous colloidal network according to claim 6, characterized in that, The step of dispersing carbomer, xanthan gum, and ammonium acryloyldimethyl taurate / behenol polyether-25 methacrylate crosspolymer in an aqueous phase specifically includes: Purified water and a chelating agent are mixed and heated to form phase A; The humectant is mixed and dispersed with the carbomer, xanthan gum and ammonium acryloyl dimethyl taurate / behenol polyether-25 methacrylate crosspolymer, and then added to phase A.

8. The method for preparing the sustained-release composition based on a composite aqueous colloidal network according to claim 6, characterized in that, The step of adding papain and oil droplets to the composite aqueous colloidal network specifically includes: The mixed phase obtained by mixing the A phase with the carbomer, xanthan gum and ammonium acryloyl dimethyl taurate / behenol polyether-25 methacrylate crosslinked polymer was cooled to 40 ℃~45 ℃. Then add the papain and oil beads.

9. The method of preparing a composite aqueous phase gel network based sustained release composition according to claim 6, wherein, It also includes one or more active ingredients selected from the following: mitochondrial energy globulin, recombinant type III collagen, sodium DNA, carnosine, serum protein, fibronectin, and elastin.

10. The use of the sustained-release composition based on a composite aqueous colloidal network according to any one of claims 1 to 5 in the preparation of skin repair bioproducts for skin repair and / or anti-aging.

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