Method for extracting piperidine phosphate serving as cosmeceutical skin care raw material

Abstract

The invention discloses a method for extracting piperidine phosphate as a cosmeceutical skin care raw material in the technical field of cosmeceutical skin care raw material preparation. The method comprises the following steps: preparing a piperazine ring water solution by fermenting genetically engineered bacteria; carrying out green synthesis on the piperaquine and 4, 7-dichloroquinoline under the action of an environment-friendly phase transfer catalyst to obtain piperaquine free alkali; then salifying with phosphoric acid, and compounding with biomimetic materials such as ceramide and sodium hyaluronate under the assistance of ultrasonic waves; and finally, carrying out low-temperature spray drying to obtain piperaquine phosphate-bionic compound powder. According to the method, biological preparation and green chemistry are combined, so that the problems of high energy consumption, large discharge amount of three wastes, organic solvent residues, more process impurities and the like in the traditional chemical synthesis route are fundamentally solved. The obtained product is high in purity, good in water solubility, good in skin compatibility and low in cytotoxicity, has multiple effects of resisting aging, repairing skin barriers and the like, and is particularly suitable for high-end cosmeceutical skin care products with high safety and low irritation.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical skincare ingredient preparation technology, specifically a method for extracting piperaquinone phosphate, a pharmaceutical skincare ingredient. Background Technology

[0002] Piperaquinone phosphate, as an important active molecule, shows promising application prospects in the field of cosmeceuticals and skincare due to its anti-inflammatory and anti-allergic properties. Its traditional industrial production mainly relies on a chemical synthesis route using 4,7-dichloroquinoline and piperazine as raw materials.

[0003] This route typically requires multi-step reactions under high temperature, strong alkalinity, and organic solvent environments. This not only leads to high energy consumption and large emissions of waste during production, but more importantly, it inevitably introduces process impurities such as unreacted raw materials, isomers, and solvent residues. The presence of these impurities poses a significant risk to cosmeceutical skincare raw materials that aim for extremely high safety and low irritation, often requiring subsequent cumbersome and costly purification steps to meet quality requirements. Furthermore, piperaquinone phosphate raw materials obtained by traditional methods may not have optimal physicochemical properties (such as crystal morphology and solubility) and skin compatibility, and their functions are relatively limited, making it difficult to meet the demands of modern high-end cosmeceutical products for diversified raw material efficacy and superior skin feel.

[0004] Therefore, there is an urgent need in this field to develop a method for preparing a novel piperaquinone phosphate raw material that can avoid the introduction of impurities from the source, has a green and gentle production process, and can directly produce a product with both high safety and excellent skin care function. Summary of the Invention

[0005] The purpose of this invention is to provide a method for extracting piperaquinone phosphate, a raw material for cosmeceuticals and skincare products, in order to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention specifically adopts the following technical solution: A method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare, comprising the following steps: S1. Bio-preparation and purification of piperazine ring: Fermentation was carried out using genetically engineered bacteria capable of synthesizing piperazine ring. The resulting fermentation broth was purified by membrane separation to obtain an aqueous solution of piperazine ring. S2, Green synthesis of piperaquine free base: The piperazine ring aqueous solution obtained in step S1 is mixed with 4,7-dichloroquinoline and reacted under the action of an environmentally friendly phase transfer catalyst to generate piperaquine free base; S3, Phosphorylation into Salt and Biomimetic Composite: The free base of piperaquine obtained in step S2 is reacted with phosphoric acid to generate piperaquine phosphate, and then biomimetic modification materials are added to carry out the composite reaction under ultrasound assistance; S4. Product molding: The reaction solution obtained in step S3 is spray-dried at low temperature to obtain the cosmeceutical grade piperaquinone phosphate-biomimetic complex.

[0007] Further, in step S1, the genetically engineered bacteria are *Escherichia coli* or *Saccharomyces cerevisiae* with exogenous lysine decarboxylase and piperazine synthase genes introduced, and the membrane separation and purification includes sequential ceramic membrane microfiltration and nanofiltration concentration.

[0008] Further, in step S1, the nanofiltration concentration uses a nanofiltration membrane with a molecular weight cutoff of 200-300 Da and an operating pressure of 0.8-1.2 MPa, resulting in a piperazine ring aqueous solution concentration of 50-100 g / L.

[0009] Further, in step S2, the environmentally friendly phase transfer catalyst is polyethylene glycol-400 or a quaternary ammonium salt, the molar ratio of the piperazine ring to 4,7-dichloroquinoline is 1.05:1 to 1.2:1, the reaction temperature is 60-75℃, and the reaction time is 2-4 hours.

[0010] Further, in step S3, the biomimetic modification material is at least one of ceramide, sodium hyaluronate, and lecithin, and its addition amount is 5%-15% of the mass of piperaquinone phosphate.

[0011] Furthermore, in step S3, the ultrasonic-assisted power is 150-300W, the frequency is 25-40kHz, the composite reaction temperature is 35-45℃, and the reaction time is 0.5-1.5 hours.

[0012] Furthermore, in step S4, the inlet temperature of the low-temperature spray drying is 100-110℃, the outlet temperature is 45-55℃, the average particle size of the obtained piperaquinone phosphate-bionic composite powder is 1-10μm, and its solubility in water at 25℃ is not less than 15g / L.

[0013] A cosmeceutical-grade piperaquinone phosphate-biomimetic complex, wherein piperaquinone phosphate is bonded to a biomimetic modification material via non-covalent bonds, the powder particle size D90 is less than 15 μm, and its 0.5% aqueous solution has a cytotoxicity level of 0-1 against human keratinocytes.

[0014] An integrated system for implementing a method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare products, the system comprising: A fermentation unit for culturing the genetically engineered bacteria and producing piperazine rings; A membrane purification unit, connected to the fermentation unit, is used for microfiltration and nanofiltration of the fermentation broth; The reaction synthesis unit, connected to the membrane purification unit, is equipped with a device for adding a phase transfer catalyst, and is used to synthesize piperaquine free base and perform phosphorylation to form salt; A biomimetic composite unit is connected to the reaction synthesis unit and equipped with an ultrasonic device for carrying out biomimetic composite reactions; A drying and molding unit, connected to the biomimetic composite unit, is used for low-temperature spray drying of the composite solution.

[0015] The application of cosmeceutical-grade piperaquinone phosphate-biomimetic complex in the preparation of cosmeceutical skin care products, which are used for anti-aging, skin barrier repair, or soothing irritation.

[0016] Compared with the prior art, the beneficial effects of the present invention are: 1. This solution uses genetically engineered bacteria to biosynthesize piperazine rings, replacing the traditional chemical synthesis of piperazine under high temperature and strong alkaline conditions. The fermentation process is mild, and energy consumption is reduced by more than 40% compared to traditional processes. Membrane separation and purification through ceramic membrane microfiltration and nanofiltration concentration replaces traditional solvent extraction. Furthermore, it uses environmentally friendly phase transfer catalysts such as polyethylene glycol-400 and quaternary ammonium salts, and uses halogen-free solvents throughout the process. Solvent residues are below the detection limit, wastewater discharge is reduced by more than 80%, and solid waste generation is significantly reduced. This effectively solves the problems of serious pollution from waste gas, wastewater, and solid waste and the difficulty in controlling solvent residues in existing technologies, and meets the green production standards of the pharmaceutical and cosmetic industry.

[0017] 2. The piperazine ring synthesized in this scheme has high purity after membrane separation and purification, and the molar ratio of piperazine ring to 4,7-dichloroquinoline is only 1.05:1-1.2:1, avoiding the pH imbalance problem caused by excessive piperazine residue in traditional processes. The process generates few impurities throughout, and combined with the mild properties of biomimetic modification materials, the final product's 0.5% aqueous solution has a cytotoxicity level of only 0.5-1 on human keratinocytes, with no risk of skin sensitization. This effectively solves the skin irritation risks caused by process impurities (unreacted raw materials, isomers) in existing technologies, and fully meets the core requirements of high safety and low irritation for cosmeceutical raw materials.

[0018] 3. This solution utilizes an ultrasound-assisted biomimetic composite process to form a non-covalent complex with skin-friendly materials such as piperaquinone phosphate, ceramides, and sodium hyaluronate. Simultaneously, low-temperature spray drying yields a micronized product with an average particle size of 2-5 μm and a D90 of less than 15 μm. Its solubility in water at 25°C is no less than 15 g / L, more than 30 times higher than traditional piperaquinone phosphate. It can be directly and uniformly dispersed in water-based skincare products, avoiding the pilling phenomenon caused by the large particle size and poor solubility of traditional products. The biomimetic modification materials can mimic the lipid structure of the stratum corneum, synergistically improving the skin barrier function and further enhancing the product's skin affinity. This effectively solves the technical shortcomings of traditional pharmaceutical-grade piperaquinone phosphate, which has poor skin compatibility and is difficult to directly apply to skincare products.

[0019] 4. The piperaquinone phosphate-biomimetic complex prepared by this method not only retains the anti-inflammatory, antioxidant, and anti-aging activities of piperaquinone phosphate itself, but also, through the functional synergy of biomimetic modification materials such as ceramide, sodium hyaluronate, and lecithin, endows the product with additional effects of skin barrier repair and soothing irritation. It achieves the integration of "multi-functionality of a single raw material", effectively solving the problem that traditional piperaquinone phosphate has a single function and cannot meet the diversified efficacy needs of modern high-end cosmeceutical products, and expanding its application scenarios in anti-aging and repair-type cosmeceutical skin care products.

[0020] 5. This solution integrates the “piperazine ring preparation-purification-piperaquinone synthesis-salt formation-biomimetic composite-molding” process into a continuous flow. The purification steps are simplified through membrane separation technology, replacing the cumbersome multiple solvent extractions and column chromatography purification in the traditional process, shortening the production cycle by more than 30%. The environmentally friendly phase transfer catalyst can be recycled and reused (recovery rate ≥85%), the cost of bio-fermentation raw materials is lower than that of chemical reagents, and the integrated system can be realized by modifying existing standardized equipment without the need for customized special equipment. The overall production cost is reduced by 20%-30% compared with the traditional process, which significantly improves the industrial application value and market competitiveness of the technology. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the steps in a method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare, according to the present invention. Figure 2 This is an integrated system diagram of a method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare, according to the present invention. Figure 3 This is a flowchart illustrating step S1 in this invention; Figure 4 This is a flowchart illustrating step S2 in this invention; Figure 5 This is a flowchart illustrating step S3 in this invention; Figure 6 This is a flowchart illustrating step S4 in this invention. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0023] This embodiment provides a method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare. Traditional industrial production mainly relies on a chemical synthesis route using 4,7-dichloroquinoline and piperazine as raw materials. This route typically requires multiple steps of reaction under high temperature, strong alkali, and organic solvent conditions. This not only leads to high energy consumption and large emissions of waste during production, but more importantly, it inevitably introduces process impurities such as unreacted raw materials, isomers, and solvent residues. The presence of these impurities poses a significant risk to cosmeceutical skincare raw materials that aim for extremely high safety and low irritation, often requiring subsequent cumbersome and costly purification steps to meet quality requirements. Furthermore, the physicochemical properties (such as crystal morphology and solubility) of piperaquinone phosphate raw materials obtained by traditional methods may not be optimal in terms of skin compatibility, and their functions are relatively limited, making it difficult to meet the demands of modern high-end cosmeceutical products for diversified raw material efficacy and superior skin feel. The following will combine... Figures 1-6 Please provide a detailed explanation: Example 1:

[0024] This embodiment provides an extraction method and integrated system for piperaquinone phosphate, a raw material for cosmeceutical skincare. This method fundamentally solves many technical problems existing in traditional chemical synthesis routes through an innovative integrated process of "biological preparation - green synthesis - biomimetic composite - low temperature molding".

[0025] In step S1 (biosynthesis and purification of piperazine rings), we first constructed a genetically engineered strain capable of efficiently synthesizing piperazine rings. Specifically, *Escherichia coli* BL21(DE3) was selected as the host bacterium. Using gene editing technology, the lysine decarboxylase gene from *Pseudomonas fluorescens* and the piperazine synthase gene from *Streptomyces* were introduced into its genome, resulting in an engineered strain capable of directly synthesizing piperazine rings using glucose as a carbon source. This engineered strain was inoculated into a modified culture medium containing 20 g / L glucose, 10 g / L soybean meal, 5 g / L yeast extract, and 2 g / L potassium dihydrogen phosphate, and cultured for 12 hours in a 50 L fermenter at 37°C, pH 7.0, and dissolved oxygen concentration of 30%. This biosynthesis method completely avoids the harsh conditions of higher temperatures (above 200°C) and higher pressures (above 2.0 MPa) required for traditional chemical synthesis of piperazine rings, reducing energy consumption by approximately 40% and eliminating the use of heavy metal catalysts at the source.

[0026] After fermentation, the resulting fermentation broth was first microfiltered through a 0.1 μm ceramic membrane at an operating pressure of 0.2 MPa and a flow rate of 1.5 m / s, effectively removing bacterial cells and other suspended particles. Subsequently, the filtrate was concentrated and desalted using a 200 Da nanofiltration membrane at an operating pressure of 0.8 MPa and a temperature of 30 °C, successfully concentrating the piperazine ring aqueous solution to a concentration of 50 g / L. This membrane separation and purification process replaced the solvent extraction and multiple crystallization steps in traditional processes, reducing wastewater discharge by more than 80% and avoiding the risk of residual organic solvents, providing high-purity raw materials for subsequent steps.

[0027] In step S2 (green synthesis of piperaquine free base), the 50 g / L piperazine ring aqueous solution obtained above was added to the reactor at a molar ratio of 1.05:1, along with 1% (by mass) of polyethylene glycol-400 as an environmentally friendly phase transfer catalyst. The reaction was carried out in a 60°C constant-temperature water bath with a stirring speed of 200 rpm for 2 hours. This green synthesis operation utilizes the unique properties of the phase transfer catalyst to effectively promote the reaction between the piperazine ring in the aqueous phase and 4,7-dichloroquine in the organic phase, achieving a conversion rate of over 98%. Compared with traditional processes, this step eliminates the need for strongly alkaline conditions and toxic organic solvents, and lowers the reaction temperature by approximately 80°C. This not only significantly saves energy consumption but also avoids the formation of isomer impurities at the source of the reaction, ensuring the high chemical purity of the intermediate piperaquine free base.

[0028] In step S3 (phosphorylation and salt formation followed by biomimetic composite), the free base of piperaquine obtained from the above reaction is first filtered and washed, then reacted with a 10% (w / w) aqueous solution of phosphoric acid at a molar ratio of 1:1.1 at 45°C for 1 hour to complete the salt formation process. Subsequently, 5% (w / w) of biomimetic modification material (in this embodiment, ceramide and sodium hyaluronate are mixed at a 1:1 mass ratio) is added, and a composite reaction is carried out in a 35°C water bath for 0.5 hours under the assistance of ultrasound at a power of 150W and a frequency of 25kHz. This innovative biomimetic composite operation utilizes the cavitation effect and mechanical vibration generated by ultrasound to significantly enhance the intermolecular interaction between piperaquine phosphate and the biomimetic material, promoting the formation of a stable complex through non-covalent bonds such as hydrogen bonds and van der Waals forces. This step not only achieves functional modification of the product but, more importantly, significantly improves its skin compatibility, laying a solid foundation for its subsequent application in cosmeceutical products.

[0029] In step S4 (product forming), the above-mentioned composite reaction solution is processed through a low-temperature spray dryer with an inlet temperature of 100℃, an outlet temperature of 45℃, and an atomization pressure of 0.4MPa, ultimately yielding a highly fluid ultrafine powder. This low-temperature drying condition effectively protects the bioactivity of the heat-sensitive piperaquinone phosphate-biomimetic complex while avoiding phase separation problems that may occur with high temperatures. The resulting product, measured by a Malvern laser particle size analyzer, has an average particle size of 2μm and a particle size distribution D90 of less than 15μm, exhibiting excellent uniformity. Solubility tests show that the product achieves a solubility of 18g / L in water at 25℃, which is 36 times higher than that of piperaquinone phosphate prepared by traditional processes (solubility approximately 0.5g / L). This characteristic allows it to better meet the formulation requirements of various water-based cosmetics.

[0030] This embodiment also provides an integrated system for implementing the above-described method. The system includes: a fermentation unit employing a 50L fully automated fermenter equipped with online monitoring and control systems for pH, dissolved oxygen, and temperature; a membrane purification unit consisting of a ceramic membrane microfiltration device and a nanofiltration concentration device connected in series for continuous operation; a reaction synthesis unit equipped with a stainless steel reactor featuring a precision metering pump and an automatic phase transfer catalyst addition device; a biomimetic composite unit, a special reactor integrating an ultrasonic generator and a temperature control system; and a drying and shaping unit employing a centrifugal spray dryer with low-temperature operation characteristics. These units are connected via food-grade piping and an intelligent control system, forming a continuous, closed, and automated production line, which not only significantly improves production efficiency but also minimizes quality fluctuations caused by human error.

[0031] This complex exhibits significant antioxidant activity, achieving an 85% DPPH free radical scavenging rate at a concentration of 0.01%. Simultaneously, in cell models, it significantly enhances the expression levels of filaggrin and naeglerin in keratinocytes, indicating its skin barrier repair function. These properties allow the product to not only retain the original anti-inflammatory and anti-aging activities of piperaquinone phosphate but also, through a biomimetic complex, endow it with additional antioxidant and barrier repair functions, achieving multiple efficacy integrations from a single ingredient.

[0032] Compared to traditional processes, this embodiment reduces energy consumption by over 40%, organic solvent usage by 95%, and wastewater discharge by 80%. Simultaneously, product purity reaches over 99.8%, cytotoxicity is reduced from the traditional 2-3 level to 0.5, and solubility is increased 36 times. This truly achieves the goals of green production and high-end product performance. This innovative technology provides the cosmeceutical industry with a new type of raw material that combines high safety, high efficacy, and good applicability, possessing significant industrialization value and broad market prospects.

[0033] Example 2:

[0034] This embodiment, based on Embodiment 1, further optimizes the process parameters, providing a more suitable extraction method for piperaquine phosphate for large-scale production. While maintaining its environmentally friendly characteristics, this method achieves a significant improvement in processing efficiency by adjusting key process parameters.

[0035] In step S1 (biopreparation and purification of piperazine rings), we used *Saccharomyces cerevisiae* as the host microorganism and derived the lysine decarboxylase gene from *Bacillus subtilis* and the piperazine synthase gene from *Streptomyces griseus* using genetic engineering techniques to construct an engineered strain with better stability. This strain was inoculated into a culture medium containing 50 g / L glucose, 15 g / L soybean meal, 8 g / L yeast extract, and 3 g / L dipotassium hydrogen phosphate, and cultured for 16 hours in a 500L fermenter at 30°C, pH 6.8, and dissolved oxygen concentration of 25%. This optimized fermentation condition increased the cell density to OD600 = 45 and significantly improved the yield of piperazine rings.

[0036] The fermentation broth was first microfiltered through a 0.2 μm pore size ceramic membrane at an operating pressure of 0.3 MPa and a flow rate of 2.0 m / s, achieving a processing capacity of 200 L / h. Subsequently, a nanofiltration membrane with a molecular weight cutoff of 300 Da was used for concentration at an operating pressure of 1.2 MPa and a temperature of 35 °C, successfully concentrating the piperazine ring aqueous solution to 100 g / L. This improvement increased the throughput per unit time by approximately 50% while extending membrane lifespan by 30%, making it more suitable for the needs of large-scale industrial production.

[0037] In step S2 (green synthesis of piperaquine free base), a 100 g / L aqueous solution of piperazine ring and 4,7-dichloroquinoline were added to a 1000 L reactor at a molar ratio of 1.2:1. A quaternary ammonium salt was added as a phase transfer catalyst at 1.5% of the total reactant mass. The reaction was carried out at 75 °C with a stirring speed of 300 rpm for 4 hours. These optimized reaction conditions further increased the conversion rate to 99.2%, while accelerating the reaction rate and increasing the unit capacity by approximately 40%. The use of the quaternary ammonium salt catalyst enhanced the stability of the heterogeneous reaction system, ensuring the reproducibility of the reaction in large-scale production.

[0038] In step S3 (phosphorylation and biomimetic compounding), the obtained piperaquine free base was reacted with a 12% phosphoric acid aqueous solution at a molar ratio of 1:1.15 at 50°C for 1.5 hours to complete the salt formation. Subsequently, 15% of the biomimetic modification material (in this embodiment, ceramide, sodium hyaluronate, and lecithin were mixed in a 1:1:1 mass ratio) was added, and the compounding reaction was carried out at 45°C for 1.5 hours under ultrasonic conditions of 300W power and 40kHz frequency. This improvement significantly enhanced the compounding effect, achieving a compounding rate of 93%, while further improving the stability of the complex. The increased proportion of biomimetic material gives the final product superior skin barrier repair function.

[0039] In step S4 (product forming), the composite reaction solution is processed using a large-scale spray dryer with an inlet temperature of 110℃, an outlet temperature of 55℃, and an atomization pressure of 0.5MPa to prepare an ultrafine powder with excellent flowability. This optimized drying condition increases the equipment's processing capacity by approximately 60%, while controlling the product's moisture content to below 1.5%. The resulting product has an average particle size of 5μm, a particle size distribution D90 of less than 15μm, and a solubility of 20g / L in water at 25℃, demonstrating excellent solubility.

[0040] The integrated system used in this embodiment is a large-scale upgrade based on Embodiment 1. The fermentation unit adopts a 500L fully automated fermentation system equipped with a more precise online monitoring probe; the membrane purification unit adopts a parallel design of multiple membrane modules to achieve continuous alternating operation; the reaction synthesis unit adopts a 1000L glass-lined reactor equipped with a high-efficiency heat exchange system; the biomimetic composite unit adopts a high-power ultrasonic system to ensure uniformity during large-scale processing; and the drying and shaping unit adopts a spray drying system with a processing capacity of 50L / h. The entire system adopts a DCS control system to achieve fully automated control of the entire process.

[0041] Quality evaluation of the final product showed that the piperaquinone phosphate-biomimetic complex maintained good physicochemical properties. Infrared spectroscopy analysis confirmed the formation of a stable non-covalent composite structure between piperaquinone phosphate and the biomimetic material. Accelerated stability testing showed that after being placed at 40℃ and 75% relative humidity for 6 months, all indicators still met quality standards. Cytotoxicity testing showed that a 0.5% aqueous solution resulted in a relative proliferation rate of over 90% in human keratinocytes, with a cytotoxicity level of Grade 1, fully meeting the safety requirements for cosmeceutical raw materials.

[0042] In terms of functional evaluation, this product demonstrates more comprehensive skincare benefits. In vitro experiments showed that at a concentration of 0.05%, it inhibited tyrosinase by 65%, indicating potential for whitening and fading dark spots; simultaneously, it significantly promoted collagen synthesis in fibroblasts, increasing collagen production by up to 45%. These properties make this product particularly suitable for the development of high-end anti-aging cosmeceutical products.

[0043] This embodiment significantly improves production efficiency while maintaining high product quality through optimized process parameters and large-scale equipment upgrades. Compared to Embodiment 1, the unit capacity of this embodiment is increased by approximately three times, and production costs are reduced by 25%, making it more suitable for the needs of large-scale industrial production. This implementation scheme provides a reliable technical path for the industrialization of pharmaceutical-grade piperaquinone phosphate-biomimetic complexes and has significant commercial value.

[0044] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare, characterized in that, The method includes the following steps: S1. Bio-preparation and purification of piperazine ring: Fermentation was carried out using genetically engineered bacteria capable of synthesizing piperazine ring. The resulting fermentation broth was purified by membrane separation to obtain an aqueous solution of piperazine ring. S2, Green synthesis of piperaquine free base: The piperazine ring aqueous solution obtained in step S1 is mixed with 4,7-dichloroquinoline and reacted under the action of an environmentally friendly phase transfer catalyst to generate piperaquine free base; S3, Phosphorylation into Salt and Biomimetic Composite: The free base of piperaquine obtained in step S2 is reacted with phosphoric acid to generate piperaquine phosphate, and then biomimetic modification materials are added to carry out the composite reaction under ultrasound assistance; S4. Product molding: The reaction solution obtained in step S3 is spray-dried at low temperature to obtain the cosmeceutical grade piperaquinone phosphate-biomimetic complex.

2. The method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare, according to claim 1, is characterized in that: In step S1, the genetically engineered bacteria are *Escherichia coli* or *Saccharomyces cerevisiae* with exogenous lysine decarboxylase and piperazine synthase genes introduced, and the membrane separation and purification includes sequential ceramic membrane microfiltration and nanofiltration concentration.

3. The extraction method for piperaquinone phosphate, a raw material for cosmeceutical skincare, according to claim 1, is characterized in that: In step S1, the nanofiltration concentration uses a nanofiltration membrane with a molecular weight cutoff of 200-300 Da and an operating pressure of 0.8-1.2 MPa, resulting in a piperazine ring aqueous solution with a concentration of 50-100 g / L.

4. The extraction method for piperaquinone phosphate, a raw material for cosmeceutical skincare, according to claim 1, is characterized in that: In step S2, the environmentally friendly phase transfer catalyst is polyethylene glycol-400 or a quaternary ammonium salt, the molar ratio of the piperazine ring to 4,7-dichloroquinoline is 1.05:1 to 1.2:1, the reaction temperature is 60-75℃, and the reaction time is 2-4 hours.

5. The extraction method for piperaquinone phosphate, a raw material for cosmeceutical skincare, according to claim 1, is characterized in that: In step S3, the biomimetic modification material is at least one of ceramide, sodium hyaluronate, and lecithin, and its addition amount is 5%-15% of the mass of piperaquinone phosphate.

6. The method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare, according to claim 1, is characterized in that: In step S3, the ultrasonic-assisted power is 150-300W, the frequency is 25-40kHz, the composite reaction temperature is 35-45℃, and the reaction time is 0.5-1.5 hours.

7. The method for extracting piperaquinone phosphate, a raw material for cosmeceutical skincare, according to claim 1, is characterized in that: In step S4, the inlet temperature of the low-temperature spray drying is 100-110℃, the outlet temperature is 45-55℃, the average particle size of the obtained piperaquinone phosphate-bionic composite powder is 1-10μm, and its solubility in water at 25℃ is not less than 15g / L.

8. A pharmaceutical-grade piperaquinone phosphate-biomimetic complex prepared by the method of any one of claims 1 to 7, characterized in that: In the complex, piperaquinone phosphate is bound to the biomimetic modification material through non-covalent bonds. Its powder particle size D90 is less than 15 μm, and its 0.5% aqueous solution has a cytotoxicity level of 0-1 to human keratinocytes.

9. An integrated system for implementing the method of claim 1, characterized in that, The system includes: A fermentation unit for culturing the genetically engineered bacteria and producing piperazine rings; A membrane purification unit, connected to the fermentation unit, is used for microfiltration and nanofiltration of the fermentation broth; The reaction synthesis unit, connected to the membrane purification unit, is equipped with a device for adding a phase transfer catalyst, and is used to synthesize piperaquine free base and perform phosphorylation to form salt; A biomimetic composite unit is connected to the reaction synthesis unit and equipped with an ultrasonic device for carrying out biomimetic composite reactions; A drying and molding unit, connected to the biomimetic composite unit, is used for low-temperature spray drying of the composite solution.

10. The application of the cosmeceutical-grade piperaquinone phosphate-biomimetic complex according to claim 8 in the preparation of cosmeceutical skincare products, characterized in that: The cosmeceutical skincare products are used for anti-aging, repairing the skin barrier, or soothing irritation.

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