Cosmetic raw material online dilution and proportioning control method and system

Abstract

The present application relates to the field of cosmetic intelligent manufacturing, and more particularly to a cosmetic raw material online dilution and proportioning control method and system, comprising the following steps: dividing the material into main dilution medium, high-concentration heat-sensitive efficacy mother liquor and compatible adjuvant, which are respectively quantitatively delivered by respective metering pumps according to a preset ratio; dividing the main dilution medium into three paths, sequentially performing annular gap pre-dilution, variable-diameter spiral deep dilution and plug flow curing on the high-concentration heat-sensitive efficacy mother liquor, and performing low-shear mixing; providing online detection at the outlet of each dilution stage, collecting spectral data in real time to quantitatively analyze the concentration of each component; and controlling the system to perform double closed-loop control of feedforward and feedback according to the concentration data of each outlet, to adjust the feed quantity of each pump, to send the qualified product to the downstream, and to return the unqualified product to the recycling. Through three-stage low-shear mixing and SERS double closed-loop control, the present application realizes high activity retention, accurate proportioning and compliant and efficient production.

Description

Technical Field

[0001] This invention relates to the field of intelligent manufacturing of cosmetics, and in particular to a method and system for online dilution and proportioning control of cosmetic raw materials. Background Technology

[0002] The ingredient formulation stage in cosmetic production is a core process that determines the product's quality and efficacy stability. Traditional cosmetic production generally employs an intermittent, manual ingredient formulation process, where raw materials are weighed manually and then mixed in a formulation tank to achieve dilution and proportioning. As the cosmetic industry moves towards intelligent and continuous processes, some companies have begun to introduce online dilution and proportioning technologies from the general chemical industry. These technologies utilize metering pumps to deliver raw materials, static mixers to complete the mixing, and general-purpose testing equipment such as refractometers and viscometers to monitor simple parameters. This technology has already seen initial application in the production of simple daily chemical products such as shampoos and shower gels.

[0003] Existing online dilution and proportioning technologies, when directly applied to the cosmetics industry, suffer from numerous technical shortcomings that make them difficult to adapt: ​​For typical high-flow-ratio, high-viscosity-difference, and heat-sensitive functional systems in the cosmetics field, strong shear mixing leads to significant degradation of active ingredients such as peptides and retinol, while low shear mixing fails to achieve uniform dispersion, creating a fundamental contradiction between achieving mixing uniformity and active ingredient retention. Existing online detection equipment can only detect comprehensive physical parameters such as refractive index and viscosity, failing to achieve specific quantitative detection of single components in complex multi-component matrices, resulting in a lack of effective basis for closed-loop control. Furthermore, the control logic of existing technologies contains fundamental errors, confusing the objects of feedforward and feedback control, making precise dynamic adjustment impossible. Moreover, most systems employ only a pure software architecture, lacking necessary hardware actuators and connections, failing to fully realize the physical operations of the production process, and thus failing to meet the GMP compliance requirements of cosmetics production and the quality control needs of high-end functional products. Summary of the Invention

[0004] To address the technical deficiencies in the background art, this invention proposes an online dilution and proportioning control method and system for cosmetic raw materials, which solves the aforementioned technical problems and meets practical needs. The specific technical solution is as follows: A method for online dilution and proportioning control of cosmetic raw materials includes the following steps: The materials of the target formula are divided into the main dilution medium, the high-concentration heat-sensitive efficacy mother liquor and the compatibility excipients, which are placed in independent sealed constant temperature storage tanks and synchronously and quantitatively delivered to the subsequent units according to the preset ratio through their respective high-precision metering pumps. The main dilution medium was divided into three streams, which were then subjected to coaxial annular gap primary pre-dilution, variable diameter spiral secondary deep dilution, and plug flow tertiary final dilution and maturation with the high-concentration thermosensitive efficacy mother liquor in sequence. The entire process was completed under low shear conditions. Online detection units are set up at the outlets of the first-stage pre-dilution, second-stage deep dilution, and third-stage final dilution to collect spectral data of materials at each stage in real time and perform single-component specific quantitative analysis to obtain the actual concentration data of each component. The central control system performs dual closed-loop full-process control combining feedforward and feedback control based on the actual concentration data at each stage. It automatically adjusts the feed parameters of each metering pump, delivers qualified materials to downstream production processes, and automatically intercepts unqualified materials to a dedicated recycling tank.

[0005] Furthermore, all the independent sealed constant temperature storage tanks adopt a sanitary-grade sealed structure and are equipped with a constant temperature control device. The storage tanks storing the main dilution medium are equipped with sanitary-grade mass flow meters, the storage tanks storing high-concentration heat-sensitive efficacy mother liquor are equipped with high-precision plunger metering pumps adapted for feeding trace amounts of efficacy ingredients, and the storage tanks storing complementary auxiliary materials are equipped with sanitary-grade gear metering pumps.

[0006] Furthermore, the specific steps for the first-stage pre-dilution of the coaxial annular gap are as follows: A portion of the main diluent is used as the primary diluent and enters the annular pipe of the coaxial annular mixer. The high-concentration thermosensitive mother liquor enters the central inner pipe of the coaxial annular mixer, forming a coaxial encapsulation flow structure in which the central mother liquor is completely encapsulated by the annular diluent. The coaxial annular gap mixer adopts a coaxial collision flow channel design without shearing components, and there are no protrusions or dead corners in the flow channel.

[0007] Furthermore, the specific steps of the variable diameter spiral two-stage depth dilution are as follows: A portion of the primary dilution medium is used as the secondary dilution medium and is then combined perpendicularly and orthogonally with the primary pre-diluted material before entering the variable diameter spiral static mixer simultaneously. The variable-diameter spiral static mixer has built-in continuously variable diameter spiral guide vanes and no additional shearing structure, relying on the fluid's own motion to achieve deep mixing.

[0008] Furthermore, the specific steps of the plug flow three-stage final dilution and ripening are as follows: The remaining main dilution medium is used as the tertiary dilution medium and is injected into the feed end of the plug flow pipeline mixer simultaneously with the secondary deep dilution material and the compatibility auxiliary materials. The push-flow pipeline mixer adopts a straight pipe design without built-in mixing components, and achieves low-temperature maturation of the system by controlling the pipeline length to adjust the material residence time.

[0009] Furthermore, the three-way flow distribution of the main dilution medium satisfies the following mathematical relationship: Q1 + Q2 + Q3 = Q0 Q1 = k1 × Q0 Q2 = k2 × Q0 Q3 = k3 × Q0 Wherein, Q0 represents the total flow rate of the main dilution medium, Q1 represents the flow rate of the primary dilution medium, Q2 represents the flow rate of the secondary dilution medium, Q3 represents the flow rate of the tertiary dilution medium, k1 represents the diversion ratio coefficient of the primary dilution medium, ranging from 0.05 to 0.10, k2 represents the diversion ratio coefficient of the secondary dilution medium, ranging from 0.15 to 0.25, and k3 represents the diversion ratio coefficient of the tertiary dilution medium, ranging from 0.65 to 0.80, and k1+k2+k3=1. The diversion ratio coefficients are dynamically fine-tuned based on the final target concentration and the online detection results.

[0010] Furthermore, the online detection unit employs a surface-enhanced Raman scattering detection unit, with a built-in noble metal nanoarray reinforcement substrate targeting the component; The online detection unit acquires real-time Raman spectral data and establishes a multi-component quantitative model of the corresponding formulation through chemometrics algorithms to eliminate matrix signal interference and achieve specific quantitative detection of single components. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the primary pre-dilution outlet, adjusting the metering pump feed parameters of the first main dilution medium and the high-concentration thermosensitive functional mother liquor, and correcting the concentration deviation in the primary pre-dilution stage. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the secondary deep dilution outlet, adjusts the feed parameters of the metering pump for the second main dilution medium, and corrects the concentration deviation in the secondary deep dilution stage. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the three-stage final dilution outlet, adjusting the metering pump feed parameters of the high-concentration heat-sensitive efficacy mother liquor and compatibility excipients; When the central control system detects that the material concentration exceeds the preset qualified threshold, it switches the unqualified material to a dedicated recovery tank through a three-way reversing valve, and at the same time triggers the fault diagnosis program to automatically adjust the operating parameters.

[0011] Furthermore, the central control system incorporates a multivariable decoupled model predictive control algorithm for the three-stage gradient dilution process, establishes dynamic input-output models for each dilution unit, and decouples the coupling relationships between process parameters. The online detection unit is equipped with an automatic calibration device that performs baseline calibration periodically.

[0012] Furthermore, it also includes online cleaning, sterilization, and production changeover control steps, as detailed below: After production is completed, the central control system automatically executes online cleaning and online sterilization procedures; When switching formulas, the central control system first automatically executes the online cleaning and online sterilization programs, and then calls the preset formula parameters to complete the parameter update and trial production verification in sequence. The online cleaning program employs a turbulent cleaning mode, sequentially using purified water, alkaline cleaning solution, purified water, acidic cleaning solution, and purified water for cyclic cleaning. The online sterilization program employs saturated steam sterilization.

[0013] A cosmetic raw material online dilution and proportioning control system includes a memory, a host computer, and a computer program stored in the memory and executable on the host computer. The computer program is configured to implement the steps of the cosmetic raw material online dilution and proportioning control method described above.

[0014] Compared with existing technologies, the online dilution and proportioning control method and system for cosmetic raw materials provided by this invention have the following beneficial effects: This invention achieves uniform mixing of systems with high flow ratios and high viscosity differences under mild conditions without active shear force through a three-stage gradient low-shear mixing process, significantly improving the activity retention rate of heat-sensitive functional ingredients. It employs surface-enhanced Raman scattering detection technology to solve the industry challenge of real-time single-component quantitative detection of trace functional components in complex matrices, providing a precise basis for closed-loop control. By clarifying the objects and logical relationships of feedforward and feedback control, a stable and reliable dual-closed-loop full-process control system is constructed, significantly improving proportioning accuracy and batch consistency. Simultaneously, a production system with complete hardware actuators and interconnections is constructed, along with standardized online cleaning, sterilization, and changeover processes, fully adapting to GMP compliance requirements for cosmetic production. This effectively reduces the risk of cross-contamination and changeover costs, enabling continuous, automated, and intelligent production of high-end cosmetic formulations. Attached Figure Description

[0015] Figure 1 This is a schematic flowchart of an online dilution and proportioning control method for cosmetic raw materials according to the present invention. Detailed Implementation

[0016] In the description of this invention, it should be understood that the terms "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "middle," and "inner," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, features defined with "first," "second," etc., may explicitly or implicitly include one or more of that feature. In the description of this invention, it should be noted that unless otherwise explicitly specified and limited, the terms "installed," "connected," and "joined" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention through specific circumstances.

[0017] The embodiments of the present invention will be described below with reference to the accompanying drawings and related examples. The embodiments of the present invention are not limited to the following examples, and the present invention relates to the relevant necessary components in this technical field, which should be regarded as well-known technology in this technical field and can be known and mastered by those skilled in this technical field.

[0018] See Figure 1 This invention provides a method for online dilution and proportion control of cosmetic raw materials, comprising the following steps: Step S100: The materials of the target formula are divided into the main dilution medium, the high-concentration heat-sensitive efficacy mother liquor and the compatibility excipients, and placed in independent sealed constant temperature storage tanks. They are then synchronously and quantitatively delivered to the subsequent units according to a preset ratio by their respective high-precision metering pumps. Specifically, based on the differences in the physical properties and formulation functions of cosmetic raw materials, a classification and control system is implemented to achieve precise and independent delivery of materials with different characteristics. The target formulation materials are divided into three categories: the main diluent is a low-viscosity Newtonian fluid, serving as the basic dispersed phase of the system; a high-concentration, heat-sensitive efficacy mother liquor is a high-viscosity, easily degradable core efficacy component, typically a pre-prepared high-concentration concentrate; and auxiliary components such as surfactants, preservatives, and pH adjusters are used. These three types of materials are stored in independent, sanitary-grade, sealed, temperature-controlled storage tanks, and are quantitatively delivered via high-precision metering pumps connected to the outlets of each tank. The central control system employs a clock-synchronized triggering mechanism to control all metering pumps to start and operate simultaneously, ensuring that all materials enter the subsequent mixing unit at the preset ratio, avoiding proportioning deviations caused by misaligned feeding sequences. The subsequent units include a coaxial annular gap mixer, a variable-diameter spiral static mixer, and a horizontal plug flow pipeline mixer.

[0019] Step S200: Divide the main dilution medium into three streams and sequentially perform coaxial annular gap primary pre-dilution, variable diameter spiral secondary deep dilution, and plug flow tertiary final dilution and maturation with the high-concentration heat-sensitive efficacy mother liquor. The entire process is completed under low shear conditions. Specifically, a stepwise dilution and staged mixing process is adopted, without applying active shear force throughout the process, relying solely on the fluid's own movement to achieve mixing, thus fundamentally resolving the contradiction between the degradation of heat-sensitive active ingredients and the uniformity of mixing. First, the main dilution medium is divided into three streams. The first stream, containing the high-concentration heat-sensitive active ingredient mother liquor, enters a coaxial annular gap mixer for primary pre-dilution. The coaxial enveloping flow structure prevents the high-viscosity mother liquor from sticking to the walls and initially reduces the system flow ratio. The second stream, containing the main dilution medium and the primary pre-diluted material, merges perpendicularly and orthogonally before entering a variable-diameter spiral static mixer for secondary deep dilution. Deep dispersion is achieved through continuous fluid rotation and radial segmentation. The third stream, containing the main dilution medium, the secondary deep-diluted material, and complementary additives, simultaneously enters a plug flow pipeline mixer for tertiary final dilution and maturation. By controlling the pipeline length, the material residence time is adjusted to allow the system's molecular chains to fully expand and reach a stable state.

[0020] Coaxial annular gap primary pre-dilution is a low-shear premixing process achieved through a coaxial annular gap mixer. High-concentration mother liquor flows out from the central inner tube, while the diluent flows out from the outer annular gap, forming a coaxial enveloped flow structure where the central mother liquor is completely enveloped by the diluent. Initial mixing is achieved through gentle collisions and laminar diffusion of the fluids, without any shear components, effectively preventing high-viscosity materials from sticking to the walls and active ingredient degradation. Variable diameter spiral secondary deep dilution is a shear-free deep mixing process achieved through a variable diameter spiral static mixer. The mixer has continuously variable diameter spiral guide vanes, causing continuous rotation, segmentation, and recombination of the fluid as it flows through. Deep dispersion is achieved through the fluid's own kinetic energy, without the need for additional shear force, and the mixing process exhibits no significant temperature rise. The plug flow three-stage final dilution and maturation is a componentless final mixing and system stabilization process. It is achieved through a straight tube with a smooth inner wall. The material flows in a plug flow state inside the tube and achieves final uniform mixing by molecular diffusion. By controlling the length of the tube, the residence time of the material is adjusted, so that the polymer components in the system can be fully expanded and the emulsion particles can be stabilized, avoiding problems such as viscosity changes and stratification after product filling.

[0021] Step S300: Online detection units are set up at the outlets of the first-stage pre-dilution, second-stage deep dilution, and third-stage final dilution to collect spectral data of materials at each stage in real time and perform single-component specific quantitative analysis to obtain the actual concentration data of each component. Specifically, online detection units are installed at the outlet pipelines of the primary pre-dilution, secondary deep dilution, and tertiary final dilution stages. These units employ surface-enhanced Raman scattering (SERS) technology and incorporate a noble metal nanoarray reinforcement substrate targeting the target component, amplifying the Raman signal of the target component by more than a million times. The detection units acquire Raman spectral data of the flowing material in real time, analyze the spectral data using a built-in chemometric algorithm, establish a multi-component quantitative model, eliminate signal interference from complex matrices, accurately obtain the actual concentration data of each component at different dilution stages, and transmit the data to the central control system in real time.

[0022] In step S400, the central control system performs dual closed-loop full-process control combining feedforward control and feedback control based on the actual concentration data of each stage. It automatically adjusts the feed parameters of each metering pump, delivers qualified materials to the downstream production process, and automatically intercepts unqualified materials to a dedicated recycling tank.

[0023] Specifically, the central control system performs feedforward control based on the actual concentration data at the primary pre-dilution outlet, automatically adjusting the feed parameters of the second main dilution medium; it also performs feedforward control based on the actual concentration data at the secondary deep dilution outlet, automatically adjusting the feed parameters of the third main dilution medium to preemptively correct concentration deviations from previous processes and prevent cumulative deviations. Simultaneously, it performs feedback control based on the actual concentration data at the tertiary final dilution outlet, adjusting the metering pump feed parameters of the high-concentration heat-sensitive mother liquor and compatible excipients in real time to ensure the final material ratio meets the formulation requirements. When the material concentration exceeds the preset acceptable threshold, the central control system immediately controls the three-way reversing valve to switch pipelines, automatically intercepting the unqualified material to a dedicated recovery tank. Simultaneously, it triggers a fault diagnosis program to automatically locate the source of the deviation and adjust operating parameters, quickly restoring normal production.

[0024] This invention achieves uniform mixing of systems with high flow ratios and high viscosity differences under mild conditions without applying active shear force through a three-stage gradient low-shear mixing process, effectively protecting the activity of heat-sensitive functional ingredients. It solves the industry problem of real-time single-component quantitative detection of trace functional components in complex multi-component matrices by employing multi-node surface-enhanced Raman scattering online detection technology. By clarifying the objects and logical relationships of feedforward and feedback control, a stable and reliable dual-closed-loop full-process control system is constructed, significantly improving proportioning accuracy and batch consistency. The fully enclosed pipeline operation avoids manual contact and cross-contamination, providing core technical support for continuous and intelligent cosmetic production.

[0025] In one embodiment of the present invention, the independent sealed constant temperature storage tanks all adopt a sanitary sealed structure and are equipped with a constant temperature control device. The storage tank storing the main dilution medium is equipped with a sanitary mass flow meter, the storage tank storing high-concentration heat-sensitive efficacy mother liquor is equipped with a high-precision plunger metering pump adapted to feed trace amounts of efficacy ingredients, and the storage tank storing complementary excipients is equipped with a sanitary gear metering pump.

[0026] Specifically, all storage tanks are integrally molded from 316L stainless steel, with the inner walls electropolished to a surface roughness Ra≤0.4μm, eliminating dead corners and weld residue to prevent material adsorption and microbial growth. The top of each tank is equipped with a sterile breather valve and a quick-install manhole. The breather valve incorporates a 0.22μm sterile filter, ensuring pressure balance within the tank while isolating it from external microbial contamination. The manhole uses a sanitary silicone sealing ring, allowing for quick disassembly for manual inspection and maintenance. The tank bottom features a conical design with an inclination angle ≥15° to ensure complete material drainage and prevent residual liquid accumulation. All seals in contact with materials are made of food-grade polytetrafluoroethylene (PTFE) to prevent leaching contamination of the raw materials.

[0027] Each storage tank is equipped with an independent jacketed constant temperature control system, achieving precise temperature control through an external circulating heat exchange unit. The main dilution medium storage tank uses ambient temperature constant temperature control with a temperature control accuracy of ±0.5℃. Temperature stability is maintained through jacket water circulation to avoid changes in the viscosity of the dilution medium due to temperature fluctuations, which could affect metering accuracy and mixing effect. The high-concentration heat-sensitive efficacy mother liquor storage tank uses low-temperature constant temperature control with a temperature control range of 4℃-25℃ and a temperature control accuracy of ±0.3℃. It is equipped with an explosion-proof refrigeration unit and temperature sensor to monitor the temperature inside the tank in real time. When the temperature exceeds the set range, the cooling or heating program is automatically activated to prevent heat-sensitive raw materials such as peptides, retinol, and probiotics from being degraded or inactivated due to temperature rise. The auxiliary material storage tank uses ambient temperature or low-temperature constant temperature control according to the characteristics of the auxiliary materials. For oily auxiliary materials that are easy to crystallize or solidify, constant temperature heating of 30℃-40℃ is used to ensure material flowability and avoid pipeline blockage.

[0028] The primary diluent is a high-flow-rate, low-viscosity Newtonian fluid, metered using a Coriolis mass flow meter. This directly measures the mass flow rate of the material, unaffected by changes in physical properties such as temperature, pressure, viscosity, and density, achieving a metering accuracy of ±0.1%. The flow meter features a hygienic design with no moving parts and a smooth, dead-angle-free flow path, allowing for online cleaning and sterilization, fully complying with cosmetic GMP requirements. The flow meter is electrically connected to the central control system, transmitting the total flow rate data of the primary diluent to the control system in real time, providing a basis for precise control of the three-way flow ratio. The high-concentration, heat-sensitive active ingredient mother liquor has characteristics of high viscosity, trace addition, and easy degradation, and is delivered using a valveless ceramic plunger metering pump. This metering pump uses a precision ceramic plunger fitted to the pump chamber with a gap ≤2μm, eliminating sealing wear and achieving a metering accuracy of ±0.05%. The minimum stable feed flow rate can reach 10nL / min, meeting the precise dosing requirements of ppm-level trace active ingredients. The pump body employs a low-shear design, with the fluid undergoing only reciprocating linear motion within the pump chamber, eliminating rotating shearing parts and preventing mechanical damage to the heat-sensitive active ingredient. The metering pump is equipped with a servo motor drive, with a response time of ≤50ms. It can adjust the feed flow rate in real time according to the instructions of the central control system to achieve dynamic and precise proportioning. The auxiliary materials used in the mixing are mostly medium-viscosity, flow-stable components, which are transported using a sanitary-grade external gear metering pump. This metering pump uses a pair of high-precision gears meshing and rotating, achieving material transport through changes in the volume of the gear teeth. The metering accuracy can reach ±0.1%, with a wide flow range and smooth, pulsation-free operation. The pump body is made of 316L stainless steel, and the gears are precision ground and polished to eliminate material residue dead zones, allowing for online cleaning. The gear metering pump has a simple structure, is easy to maintain, and has a moderate cost, making it suitable for the stable transport of common auxiliary materials such as surfactants, preservatives, and pH adjusters.

[0029] In one embodiment of the present invention, the specific steps of the coaxial annular gap primary pre-dilution are as follows: A portion of the main diluent is used as the primary diluent and enters the annular pipe of the coaxial annular mixer. The high-concentration thermosensitive mother liquor enters the central inner pipe of the coaxial annular mixer, forming a coaxial encapsulation flow structure in which the central mother liquor is completely encapsulated by the annular diluent. The coaxial annular gap mixer adopts a coaxial collision flow channel design without shearing components, and there are no protrusions or dead corners in the flow channel.

[0030] Specifically, the coaxial annular mixer adopts a one-piece molded structure of 316L stainless steel, consisting of a central inner tube and an outer annular pipe coaxially nested. The diameter ratio of the inner tube to the outer tube is controlled between 1:4 and 1:6 to ensure sufficient flow area in the annular channel, while preventing the central mother liquor stream from contacting the inner wall of the outer tube. All inner walls of the flow channels are electrolytically polished, with a surface roughness Ra≤0.4μm. The welds are automatically argon arc welded and mirror polished, free of any protrusions, burrs, or weld residue. The first main dilution medium (primary dilution medium) enters the outer annular pipe from the side inlet of the mixer and flows uniformly along the axial direction; the high-concentration heat-sensitive mother liquor enters the central inner tube from the rear center inlet of the mixer and flows forward along the axial direction. The central control system adjusts the outlet pressure of the two metering pumps to ensure that the flow velocity of the annular dilution medium is slightly higher than that of the central mother liquor. This creates a stable coaxial enveloping flow structure at the mixer outlet, consisting of a central mother liquor column and an outer dilution medium layer. The central mother liquor never contacts the inner wall of the mixer, completely eliminating the problem of high-viscosity materials adhering to the wall. The outlet of the central inner pipe adopts a gradually expanding structure of 15° to 30°, allowing the central mother liquor to diffuse slowly and evenly as it flows out of the inner pipe, avoiding turbulent shearing caused by sudden changes in flow velocity. The outlet of the annular pipe adopts a gradually contracting structure of 10° to 20°, causing the outer dilution medium to accelerate slightly at the outlet, forming a stable enveloping layer and preventing the central mother liquor from diffusing to the pipe wall. The internal flow channel of the coaxial annular mixer is entirely free of any active shearing components such as shearing teeth, baffles, agitators, or protrusions, as well as dead angles, steps, or blind holes that could cause stagnation. The fluid within the flow channel only undergoes axial flow and radial diffusion, without generating any additional mechanical shearing forces. The mixer's collision chamber employs a spherical transition design, allowing the two fluid streams to smoothly change direction after collision, avoiding localized turbulence. The central mother liquor and the annular dilution medium collide coaxially at the mixer's outlet collision chamber. The kinetic energy of the two fluids is converted into mixing energy, initially breaking the central mother liquor into fine droplets, which are then uniformly dispersed in the dilution medium through laminar diffusion. The collision intensity is controlled by adjusting the velocity difference between the two fluid streams, maintaining a velocity difference between 0.5 m / s and 1.5 m / s to ensure sufficient mixing energy without generating strong shear or temperature rise. During the first-stage pre-dilution process, the Reynolds number of the fluid within the mixer is controlled below 2000, maintaining laminar flow and avoiding turbulent shear. The temperature rise during the mixing process is ≤0.5℃, fully meeting the temperature requirements of heat-sensitive raw materials such as peptides, retinol, and enzyme preparations. After primary pre-dilution, the flow ratio of high-concentration thermosensitive efficacy mother liquor to primary dilution medium is reduced from the initial 1:1000 or more to between 1:20 and 1:50, completely eliminating the "core flow" phenomenon in which trace amounts of mother liquor cannot be evenly dispersed in a high flow ratio system, and the premixing uniformity is ≥90%.

[0031] In one embodiment of the present invention, the specific steps of the variable diameter spiral two-stage depth dilution are as follows: A portion of the primary dilution medium is used as the secondary dilution medium and is then combined perpendicularly and orthogonally with the primary pre-diluted material before entering the variable diameter spiral static mixer simultaneously. The variable-diameter spiral static mixer has built-in continuously variable diameter spiral guide vanes and no additional shearing structure, relying on the fluid's own motion to achieve deep mixing.

[0032] Specifically, a vertically orthogonal dual-inlet structure is set at the feed end of the variable-diameter spiral static mixer. The primary pre-diluted material enters the mixer from the axial inlet, while the second main dilution medium (secondary dilution medium) is injected vertically from the radial inlet. The two fluids collide vertically at 90° in the mixer's inlet chamber. The inlet chamber adopts a spherical transition design, without right angles or steps, to avoid local turbulence and dead zones caused by fluid impact. The central control system adjusts the feed pressure and flow rate of the secondary dilution medium in real time according to the flow rate and viscosity of the primary pre-diluted material, keeping the momentum ratio of the two fluids between 1:1 and 1:1.5. This momentum ratio ensures sufficient convergence and penetration of the two fluids, while avoiding fluid splashing and enhanced shearing caused by excessive momentum difference. An annular distributor is set at the radial inlet to ensure uniform injection of the secondary dilution medium along the circumference, avoiding unilateral flow deviation. The inner wall of the inlet chamber is treated with ultra-electrolytic polishing, with a surface roughness Ra≤0.2μm, to prevent high-viscosity materials from sticking to the wall in the convergence zone. The variable-diameter spiral static mixer features a one-piece molded structure made of 316L stainless steel. The shell is cylindrical, with a continuous spiral guide vane inside. The vane and shell are seamlessly welded together, and the weld joints are mirror-polished, leaving no weld seam residue or gaps. The gap between the vane and the inner wall of the shell is ≤0.1mm, completely eliminating dead zones for material stagnation. The spiral guide vane employs a continuously variable-diameter design; from the mixer inlet to the outlet, the vane diameter gradually increases and then gradually decreases, forming an alternating "expansion-contraction" flow channel structure. The helix angle of the vane remains constant between 15° and 20°, while the pitch changes synchronously with the diameter, ensuring a relatively stable axial flow velocity of the fluid within the flow channel. This variable-diameter design allows the fluid to undergo continuous compression-expansion motion during flow, enhancing the radial mixing effect. After entering the mixer, the fluid is continuously divided into multiple thin layers by the spiral guide vane, while simultaneously rotating with the vane. Under the action of the variable-diameter flow channel, the radial velocity of the fluid constantly changes, generating strong radial convection and molecular diffusion, allowing fluid layers of different concentrations to fully penetrate and blend. Throughout the mixing process, the fluid is only guided by the blades, without any active shear forces such as rotational shear or impact shear, and the shear rate is ≤100s. -1The temperature rise during the mixing process is ≤1℃, fully meeting the protection requirements for heat-sensitive active ingredients. During the two-stage deep dilution process, the Reynolds number of the fluid in the mixer is controlled between 1500 and 2500, in a transitional state between laminar and weakly turbulent flow, ensuring sufficient mixing energy while avoiding shear enhancement caused by strong turbulence. After the two-stage deep dilution, the flow ratio of the high-concentration heat-sensitive active ingredient to the total dilution medium is further reduced to between 1:100 and 1:200, with a mixing uniformity ≥95% and no visible agglomerates or fisheyes.

[0033] In one embodiment of the present invention, the specific steps of the plug flow three-stage final dilution and ripening are as follows: The remaining main dilution medium is used as the tertiary dilution medium and is injected into the feed end of the plug flow pipeline mixer simultaneously with the secondary deep dilution material and the compatibility auxiliary materials. The push-flow pipeline mixer adopts a straight pipe design without built-in mixing components, and achieves low-temperature maturation of the system by controlling the pipeline length to adjust the material residence time.

[0034] Specifically, the central control system employs a high-precision clock synchronization triggering mechanism to simultaneously start and synchronously adjust the flow rates of the secondary deep dilution material delivery pump, the third main dilution medium delivery pump, and the auxiliary material delivery pump. This ensures that the three materials arrive at the feed end of the plug flow pipeline mixer at the same time, eliminating ratio fluctuations caused by differences in feed timing. The feed end of the plug flow pipeline mixer is equipped with an integrated annular distributor. The distributor has evenly spaced feed holes corresponding to the material quantities. The secondary deep dilution material enters through the central axial hole, the third main dilution medium is evenly injected through the inner ring radial holes, and the auxiliary materials are evenly injected through the outer ring radial holes. This distribution method allows the three materials to form a uniform annular stratified structure before entering the straight pipe section, avoiding localized material accumulation or flow deviation. The central control system adjusts the feed pressure of the three materials in real time, keeping the outlet pressure difference within ±0.02MPa to ensure that each material enters the straight pipe section at the same flow rate, preventing fluid cross-flow and uneven mixing caused by pressure differences. For materials with significant viscosity differences, the flow rate differences caused by viscosity are compensated by fine-tuning the feed orifice diameter, ensuring a stable fluid state after mixing. The plug flow mixer is integrally formed from food-grade 316L stainless steel seamless pipe, without any welded joints or seams. The inner wall of the pipe undergoes high-precision electrolytic polishing, with a surface roughness Ra≤0.4μm, free of burrs, pits, and scratches, minimizing material adsorption and residue. Both ends of the pipe are connected with sanitary quick-release clamps, allowing for quick disassembly for manual inspection and maintenance. Unlike traditional mixers with built-in baffles, packing, and agitators, this plug flow mixer has no internal components that obstruct fluid flow. The fluid flows axially at a uniform velocity within the pipe, without any rotational shear, impact shear, or turbulent shear; the shear rate is ≤10s. -1The mixing process generates no temperature rise, completely avoiding mechanical damage and thermal degradation of heat-sensitive active ingredients. Simultaneously, the component-free design eliminates any stagnant zones or dead angles within the pipeline, enabling continuous turbulence during CIP cleaning. Post-cleaning, the residual material content is ≤10ppb, fully meeting the cleaning validation requirements of cosmetic GMP. The fluid in the plug flow pipeline exhibits an ideal piston flow state, with an axial backmixing coefficient ≤0.01, ensuring uniform residence time for all material particles within the pipe. The residence time is calculated using the formula T=L / V (where T is the residence time, L is the total pipeline length, and V is the average fluid velocity). The central control system can precisely control the residence time between 10s and 60s by adjusting the total pipeline length (using modular pipeline splicing) or fluid velocity, based on the characteristics of different formulations. Cosmetic formulations widely contain polymeric thickeners (carbomer, xanthan gum, hyaluronic acid), emulsifiers, and active ingredients. After mixing, these require a certain amount of time to allow for molecular chain expansion, hydrogen bond formation, and emulsion particle rearrangement to reach a stable thermodynamic state. Traditional online mixing technology uses a "mix and use" approach, directly filling the system before it has fully matured, which can lead to problems such as increased viscosity, stratification, coarsening, and water separation during the shelf life. This invention utilizes a plug flow pipeline for natural residence time, allowing the system to fully mature under room temperature and shear-free conditions. This ensures that the polymeric molecular chains are fully expanded, the emulsion particles are evenly distributed, and the system viscosity and stability reach their optimal state. For systems containing polymeric thickeners, a residence time of 30 to 60 seconds is set to ensure full molecular chain expansion; for simple homogeneous solution systems, a residence time of 10 to 20 seconds is sufficient; and for semi-solid systems containing emulsion particles, a residence time of 20 to 40 seconds is set to ensure emulsion particle stability. After three-stage final dilution and maturation, the mixing uniformity of the system is ≥99.5%, and the shelf-life stability after filling is more than 3 times better than that of traditional online mixing technology.

[0035] It should be noted that the three-way flow distribution of the main dilution medium satisfies the following mathematical relationship: Q1 + Q2 + Q3 = Q0 Q1 = k1 × Q0 Q2 = k2 × Q0 Q3 = k3 × Q0 Where Q0 represents the total flow rate of the main dilution medium, which is the volumetric flow rate of all the main dilution medium output from the main dilution medium storage tank per unit time.

[0036] Q1 represents the flow rate of the primary dilution medium, Q2 represents the flow rate of the secondary dilution medium, and Q3 represents the flow rate of the tertiary dilution medium; k1 represents the splitting ratio coefficient of the primary dilution medium, ranging from 0.05 to 0.10, based on the initial concentration of the high-concentration heat-sensitive mother liquor. and the target concentration after primary pre-dilution Through formula The calculation shows that, among which This is the feed flow rate for high-concentration mother liquor. It also needs to meet the flow rate ratio required for the first-stage pre-dilution. This ensures that the coaxial annular gap mixer can achieve effective mixing.

[0037] k2 represents the split ratio coefficient of the secondary dilution medium, with a value ranging from 0.15 to 0.25, based on the target concentration after primary pre-dilution. and the target concentration after secondary deep dilution Through formula The calculation shows that the flow rate ratio for secondary deep dilution must also be met. This ensures the mixing effect of the variable diameter spiral static mixer.

[0038] k3 represents the splitting ratio coefficient of the three-stage dilution medium, with a value ranging from 0.65 to 0.80. Based on the law of conservation of flow, it is calculated using the formula... The calculation shows that no separate settings are required. This calculation method ensures that the sum of the three-way split ratios is always 1, and the total flow remains constant.

[0039] Furthermore, k1+k2+k3=1, and the diversion ratio coefficient is dynamically fine-tuned based on the final target concentration and the online detection results.

[0040] In one embodiment of the present invention, the online detection unit employs a surface-enhanced Raman scattering detection unit, with a built-in noble metal nanoarray reinforcement substrate for the target component; The online detection unit acquires real-time Raman spectral data and establishes a multi-component quantitative model of the corresponding formulation through chemometrics algorithms to eliminate matrix signal interference and achieve specific quantitative detection of single components. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the primary pre-dilution outlet, adjusting the metering pump feed parameters of the first main dilution medium and the high-concentration thermosensitive functional mother liquor, and correcting the concentration deviation in the primary pre-dilution stage. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the secondary deep dilution outlet, adjusts the feed parameters of the metering pump for the second main dilution medium, and corrects the concentration deviation in the secondary deep dilution stage. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the three-stage final dilution outlet, adjusting the metering pump feed parameters of the high-concentration heat-sensitive efficacy mother liquor and compatibility excipients; When the central control system detects that the material concentration exceeds the preset qualified threshold, it switches the unqualified material to a dedicated recovery tank through a three-way reversing valve, and at the same time triggers the fault diagnosis program to automatically adjust the operating parameters.

[0041] Specifically, the enhancement substrate built into the online detection unit adopts a gold nanorod array structure. Periodically arranged gold nanorods are fabricated on a quartz substrate using electron beam lithography. The aspect ratio of the nanorods is controlled between 3:1 and 5:1. The surface plasmon resonance peak is matched with the 785nm excitation wavelength used for detection, resulting in an enhancement factor ≥10. 6 It can amplify the Raman scattering signal of target molecules by more than a million times, with a detection limit of 0.1 ppb, meeting the detection requirements for trace active ingredients at the ppm level. The substrate surface is hydrophobically modified to reduce non-specific adsorption, and the service life is ≥30 days. The detection cell is integrally molded from 316L stainless steel, with a straight-through flow channel structure, no dead corners or stagnant areas, and an inner wall roughness Ra≤0.4μm, allowing for online cleaning and online sterilization. Optical windows are set on both sides of the detection cell, made of sapphire, with a light transmittance ≥90% and resistance to acid and alkali corrosion. The inner diameter of the flow channel is controlled between 2mm and 4mm to ensure stable material flow rate while reducing sample volume and detection lag time. A 785nm narrow-linewidth semiconductor laser is used as the excitation source, with adjustable output power (0-500mW), and equipped with a high-sensitivity back-illuminated CCD detector, with a spectral resolution ≤2cm. -1 The spectral acquisition range is 400cm. -1 Up to 2000cm -1 The system integrates automatic focusing and automatic calibration functions, automatically performing baseline and standard calibration every 2 hours to ensure the long-term stability of test data. With a detection response time of ≤200ms, it can achieve real-time online detection of continuous flow materials.

[0042] The acquired raw Raman spectral data are first preprocessed, including fluorescence background subtraction, baseline correction, smoothing and denoising, and normalization, to eliminate the effects of instrument noise, fluorescence interference, and light source intensity fluctuations. Adaptive iterative reweighted penalized least squares (airPLS) is used for baseline correction to effectively remove strong fluorescence background caused by complex matrices. A multi-component quantitative model is established using partial least squares regression (PLSR). For each target formulation, standard samples with different concentration gradients are prepared in advance, and their Raman spectral data are collected. The spectral data are correlated with corresponding known concentration data, and model parameters are optimized through cross-validation to establish quantitative correction models for each component. After model establishment, independent validation sets are used for verification to ensure quantitative accuracy ≤ ±0.5%. When formulations are switched or raw material batches change, the system supports rapid model updates and imports. Operators only need to import the standard sample spectral data of the new formulation, and the system can automatically complete model retraining and validation without replacing hardware, significantly improving the system's formulation adaptability.

[0043] The central control system collects real-time data on the actual concentration of the high-concentration, heat-sensitive mother liquor at the primary pre-dilution outlet and compares it with the primary target concentration to calculate the deviation. If the actual concentration is too high, it indicates that the flow rate of the primary diluent is too low or the mother liquor flow rate is too high. The system automatically increases the flow rate of the primary diluent metering pump or decreases the flow rate of the mother liquor metering pump proportionally. If the actual concentration is too low, the system adjusts in the opposite direction. The control cycle is 100ms, and the response time is ≤500ms, directly correcting the source of the deviation and preventing it from entering the secondary mixer. Real-time data on the actual concentration at the secondary deep dilution outlet is collected and compared with the secondary target concentration to calculate the deviation. This deviation is caused only by fluctuations in the flow rate of the secondary primary diluent (the primary deviation has been corrected). The system directly adjusts the feed parameters of the secondary primary diluent metering pump to correct the concentration deviation in the secondary dilution stage. This control loop is independent of the primary loop, with no parameter coupling, significantly improving stability. Real-time data on the actual concentration of all components at the tertiary final dilution outlet is collected and compared with the final target concentration of the formulation to calculate the overall deviation. This circuit is used to correct for unforeseen slow disturbances such as batch differences in raw materials, long-term wear and tear of equipment, and fluctuations in ambient temperature. It also fine-tunes the metering pump feed parameters of high-concentration heat-sensitive active ingredients and compatible excipients, so as to stabilize the final proportioning accuracy within ±0.1%.

[0044] When the concentration deviation at the primary pre-dilution outlet is within the preset "dilutionable range" (usually within ±5%), and the system detects a temporary malfunction in the primary metering pump that cannot be immediately adjusted, a temporary deviation dilution strategy can be initiated. The central control system automatically calculates the required increase in the flow rate of the second main dilution medium and dilutes the primary deviation to within the acceptable range by increasing the secondary dilution volume. Simultaneously, a primary metering pump malfunction alarm is triggered, notifying operators to perform maintenance. The deviation dilution strategy must not run continuously for more than 5 minutes at a time, and it must terminate immediately if the deviation exceeds ±5%, executing a non-conforming product interception procedure to avoid disrupting the tertiary flow distribution ratio and mixing uniformity.

[0045] The central control system compares the actual concentration data at the final dilution outlet of the three-stage system with the preset acceptable threshold in real time. When the data exceeds the acceptable range for three consecutive tests, a switching command is immediately sent to the three-way reversing valve to switch the non-conforming material to a dedicated recovery tank. The three-way reversing valve uses a sanitary pneumatic diaphragm valve with a switching response time of ≤100ms, ensuring complete interception of non-conforming products. Simultaneously, the system issues an audible and visual alarm to prompt operators to handle the situation. When a concentration deviation is detected, the system automatically triggers a fault diagnosis program to locate the source of the fault based on the type, magnitude, and trend of the deviation. For example, if the concentration deviation is consistently high and gradually increasing, it may indicate wear on the high-concentration mother liquor metering pump; if the concentration deviation is a sudden fluctuation, it may indicate that the raw material tank level is too low or that air bubbles have appeared in the pipeline. After locating the fault, the system automatically takes corresponding repair measures, such as adjusting the metering pump compensation coefficient and initiating the pipeline venting program. If automatic repair is not possible, an alarm is issued and the system is shut down to prevent the generation of more non-conforming products.

[0046] It should be noted that the central control system has a built-in multivariable decoupled model predictive control algorithm for the three-stage gradient dilution process, which establishes the input-output dynamic model of each dilution unit and decouples the coupling relationship between each process parameter. The online detection unit is equipped with an automatic calibration device that performs baseline calibration periodically.

[0047] Specifically, for the three-stage gradient dilution process of this invention, a dynamic input-output model for each dilution unit is established using a step response test method. The system's input variables include: the flow rates of the first main dilution medium, the second main dilution medium, the third main dilution medium, the high-concentration thermosensitive active ingredient mother liquor, and the flow rates of the complementary excipients; the output variables include: the outlet concentration of the first-stage pre-dilution, the outlet concentration of the second-stage deep dilution, the outlet concentration of the third-stage final dilution, and the total pipeline pressure. Output response data under step changes of different input variables are collected experimentally, and the transfer function matrix between each variable is fitted to construct the system's state-space model. The model's prediction time domain is set to 10 steps, and the control time domain is set to 3 steps, enabling accurate prediction of the system's output changes within the next 10 sampling periods. A feedforward decoupling method is adopted, introducing a decoupling compensator within the model predictive control framework. The decoupling compensation matrix is ​​calculated based on the transfer function matrix, transforming the multivariable coupled system into multiple independent single-variable subsystems, eliminating mutual interference between process parameters. For example, when adjusting the flow rate of the second main dilution medium, the decoupling compensator automatically calculates the impact of this adjustment on the outlet pressure of the first-stage pre-dilution and the flow rate of the third main dilution medium, and compensates for the relevant parameters in advance to avoid parameter fluctuations being transmitted to subsequent processes. The coupling degree of the decoupled system is ≤5%, and there is basically no mutual interference between the control loops. The algorithm adopts a rolling optimization control strategy. Within each sampling period (100ms), based on the current system state and future output prediction, it solves for the optimal control sequence in the finite time domain, executes only the first control action, and recalculates the optimization in the next sampling period to achieve closed-loop rolling control. At the same time, the actual concentration data collected by the online detection unit is used for feedback correction to correct model prediction errors and eliminate the impact of unforeseen disturbances such as raw material property fluctuations and equipment wear. The optimization objective function is set as a weighted sum of minimizing concentration deviation and minimizing control quantity change, which ensures the accuracy of the proportioning while avoiding frequent and large-scale adjustments of the metering pumps and extending the service life of the equipment. The algorithm has built-in strict process constraints, including the maximum and minimum flow limits of each metering pump, pipeline pressure safety thresholds, and mixer shear rate limits. During the optimization calculation process, all control variables must meet the constraints to ensure that the system operates within a safe process range and avoids problems such as equipment overload and active material degradation. When abnormal disturbances occur in the system, the algorithm will automatically adjust the control strategy to prioritize the safe and stable operation of the system.

[0048] Each online detection unit is equipped with an independent automatic calibration device, including a standard storage tank, a micro-injection pump, a three-way switching valve, and a waste liquid collection tank. The standard storage tank uses light-proof brown glass bottles containing pre-calibrated standard solutions with concentrations matching the detection range of the target components, and has a shelf life of ≥6 months. The micro-injection pump is a high-precision plunger pump with a metering accuracy of ±0.05%, enabling precise quantitative injection of standards. The three-way switching valve is a sanitary pneumatic diaphragm valve with a switching response time ≤100ms, allowing for rapid switching between material flow and standard flow. The system automatically performs baseline calibration every 2 hours. During calibration, the three-way switching valve switches to the purified water channel, circulates purified water into the detection tank, and collects the Raman spectrum of the purified water as the background baseline. The system's background subtraction parameters are automatically updated to eliminate baseline shifts caused by factors such as light source drift and optical window contamination. The baseline calibration time is ≤30s. After calibration, the system automatically switches back to the material flow channel, resuming normal detection without affecting continuous production. The system automatically performs standard calibration every 7 days. During calibration, the system first switches to the purified water channel to rinse the detection tank, then switches to the standard channel, introduces a quantitative standard solution into the detection tank, collects the Raman spectrum of the standard, compares it with the pre-stored standard spectrum, and calculates the detection deviation. If the deviation is within ±0.3%, the system automatically updates the correction coefficient of the quantitative model; if the deviation exceeds ±0.3%, the system issues an alarm, notifying the operator to replace the standard or check the detection unit. After calibration, the detection tank is rinsed three times with purified water to ensure no standard residue remains, then the system switches back to the material flow channel. All calibration data (including calibration time, baseline spectrum, standard spectrum, deviation value, and correction coefficient) are automatically stored in the central control system for ≥3 years, allowing for easy retrieval and traceability, meeting the full-process traceability requirements of cosmetic GMP. The system supports custom settings for the calibration cycle, allowing operators to adjust the calibration frequency according to actual production conditions.

[0049] In one embodiment of the present invention, an online cleaning, sterilization, and production changeover control step is further included, as follows: After production is completed, the central control system automatically executes online cleaning and online sterilization procedures; When switching formulas, the central control system first automatically executes the online cleaning and online sterilization programs, and then calls the preset formula parameters to complete the parameter update and trial production verification in sequence. The online cleaning program employs a turbulent cleaning mode, sequentially using purified water, alkaline cleaning solution, purified water, acidic cleaning solution, and purified water for cyclic cleaning. The online sterilization program employs saturated steam sterilization.

[0050] Specifically, the online cleaning program employs forced turbulence cleaning technology. The central control system adjusts the output pressure of the cleaning pump to ensure the Reynolds number of the cleaning fluid in the pipeline is ≥3000, creating a strong turbulent flushing effect. Under turbulent conditions, the cleaning fluid effectively removes residual materials from the inner walls of the pipeline, mixer blades, and valve gaps, solving the problem of dead-angle residues that laminar flow cleaning cannot remove. The system has built-in flow and pressure sensors to monitor the flow rate and pressure of the cleaning fluid in real time. When the Reynolds number falls below a set threshold, the pump output power is automatically increased to ensure consistent cleaning results throughout the process. The cleaning process strictly follows the sequence of "purified water pre-rinse → alkaline cleaning fluid circulation → purified water intermediate rinse → acidic cleaning fluid circulation → purified water final rinse." The cleaning time for each step is automatically adjusted according to the material characteristics, ranging from 10 to 30 minutes, as detailed below: Pre-rinse with purified water: Rinse the pipeline with purified water at room temperature to remove most of the loose residual material; the rinsing wastewater is discharged directly. Alkaline cleaning solution is circulated, using a 0.5%-1% sodium hydroxide solution, heated to 40-50℃ for circulation cleaning, effectively dissolving organic residues such as grease, protein, and polysaccharides; Rinse with purified water in between, and rinse with room temperature purified water until the pH of the effluent is neutral to remove residual alkaline cleaning solution; Acidic cleaning solution is circulated, using a 0.1%-0.3% citric acid solution, and circulated at room temperature to remove scale, mineral deposits and metal oxides from the pipeline; Final rinse with purified water, using injection-grade purified water until the conductivity of the effluent is ≤2μS / cm, ensuring no cleaning media residue remains.

[0051] The system employs an online saturated steam sterilization program. After cleaning, the SIP sterilization program is automatically executed, using saturated steam at 121℃ and 0.1MPa for 15-30 minutes. Drainage valves are installed at the lowest points of the pipelines, valve connections, and mixer outlets—locations prone to condensation—to automatically drain condensate and ensure a uniform temperature above 121℃ throughout the system, eliminating sterilization cold spots. After sterilization, sterile compressed air is automatically introduced to dry the pipelines, preventing residual moisture from promoting microbial growth.

[0052] Before switching formulas, the system must first execute a complete online cleaning and sterilization procedure to thoroughly remove all residual materials from the previous formula. For special formulas containing fragrances, preservatives, or allergens, the system will automatically add an alkaline cleaning and final rinsing step to ensure that the residue level is ≤10ppb, fully complying with the requirements for cross-contamination control in cosmetics. After cleaning and sterilization, the system automatically generates a cleaning validation report, recording key parameters such as cleaning time, temperature, pressure, and conductivity, serving as the basis for GMP compliance traceability. After cleaning and sterilization, the operator selects the target formula in the central control system. The system automatically calls the pre-stored formula parameter package and updates all process parameters with one click, including: total flow rate of the main diluent, three-way flow ratio coefficient, feed flow rate of each raw material metering pump, tank temperature, mixer operating parameters, SERS detection model, and qualified concentration threshold. The parameter update process does not require manual modification, avoiding human error, and the update time is ≤1 minute. After the parameters are updated, the system automatically enters trial production mode: First, purified water is introduced and run for 5 minutes to test the operating status of each metering pump, valve, and sensor; then, a small amount of material is introduced according to the formula ratio, and after three-stage mixing, the material concentration is detected by the SERS detection unit at the third-stage outlet. If the test results are within the acceptable range for three consecutive times, the system automatically switches to continuous production mode; if the test results are unacceptable, the system automatically adjusts the relevant parameters and recalibrates until they are acceptable. All unacceptable materials generated during the trial production process are discharged into a dedicated recovery tank and do not flow into downstream processes.

[0053] This invention achieves uniform mixing of thermosensitive functional systems with high flow ratios and high viscosity differences under mild conditions with no active shear force and no significant temperature rise throughout the process through a three-stage gradient low-shear mixing process. This completely solves the industry pain point of the trade-off between mixing uniformity and active ingredient retention, increasing the activity retention rate of thermosensitive functional raw materials to over 95%. Through differentiated raw material pretreatment and metering equipment configuration, and a precise flow distribution mathematical model, stable delivery and precise diversion of materials with different physical properties are ensured from the source, laying a solid foundation for subsequent mixing and control. Furthermore, by combining surface-enhanced Raman scattering online detection technology with a multivariable decoupled model predictive control algorithm, this invention achieves for the first time in cosmetics… Real-time single-component quantitative detection and stable closed-loop control of ppm-level trace active ingredients in complex multi-component matrices ensure stable ratio accuracy within ±0.1% and batch-to-batch content fluctuation ≤0.2%, significantly improving product quality consistency. Simultaneously, through standardized and automated online cleaning, sterilization, and changeover control processes, it fully meets the microbial control and cross-contamination prevention requirements of cosmetic GMP, with post-cleaning material residue ≤10ppb and changeover time reduced from several hours to less than 30 minutes, greatly improving production flexibility and economy. This provides a complete and industrially feasible core technology solution for the continuous, intelligent, and compliant production of high-end cosmetics.

[0054] The present invention also provides an online dilution and proportioning control system for cosmetic raw materials, including a memory, a host computer, and a computer program stored in the memory and executable on the host computer. The computer program is configured to implement the steps of the online dilution and proportioning control method for cosmetic raw materials as described above.

[0055] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for online dilution and proportioning control of cosmetic raw materials, characterized in that, Includes the following steps: The materials of the target formula are divided into the main dilution medium, the high-concentration heat-sensitive efficacy mother liquor and the compatibility excipients, which are placed in independent sealed constant temperature storage tanks and synchronously and quantitatively delivered to the subsequent units according to the preset ratio through their respective high-precision metering pumps. The main dilution medium was divided into three streams, which were then subjected to coaxial annular gap primary pre-dilution, variable diameter spiral secondary deep dilution, and plug flow tertiary final dilution and maturation with the high-concentration thermosensitive efficacy mother liquor in sequence. The entire process was completed under low shear conditions. Online detection units are set up at the outlets of the first-stage pre-dilution, second-stage deep dilution, and third-stage final dilution to collect spectral data of materials at each stage in real time and perform single-component specific quantitative analysis to obtain the actual concentration data of each component. The central control system performs dual closed-loop full-process control combining feedforward and feedback control based on the actual concentration data at each stage. It automatically adjusts the feed parameters of each metering pump, delivers qualified materials to downstream production processes, and automatically intercepts unqualified materials to a dedicated recycling tank.

2. The method for online dilution and proportioning control of cosmetic raw materials according to claim 1, characterized in that, All independent, sealed, constant-temperature storage tanks adopt a sanitary-grade sealed structure and are equipped with a constant-temperature control device. The storage tanks storing the main dilution medium are equipped with sanitary-grade mass flow meters, the storage tanks storing high-concentration heat-sensitive efficacy mother liquor are equipped with high-precision plunger metering pumps adapted for feeding trace amounts of efficacy ingredients, and the storage tanks storing complementary excipients are equipped with sanitary-grade gear metering pumps.

3. The method for online dilution and proportioning control of cosmetic raw materials according to claim 1, characterized in that, The specific steps for the first-stage pre-dilution of the coaxial annular gap are as follows: A portion of the main diluent is used as the primary diluent and enters the annular pipe of the coaxial annular mixer. The high-concentration thermosensitive mother liquor enters the central inner pipe of the coaxial annular mixer, forming a coaxial encapsulation flow structure in which the central mother liquor is completely encapsulated by the annular diluent. The coaxial annular gap mixer adopts a coaxial collision flow channel design without shearing components, and there are no protrusions or dead corners in the flow channel.

4. The method for online dilution and proportioning control of cosmetic raw materials according to claim 1, characterized in that, The specific steps of the variable diameter spiral two-stage depth dilution are as follows: A portion of the primary dilution medium is used as the secondary dilution medium and is then combined perpendicularly and orthogonally with the primary pre-diluted material before entering the variable diameter spiral static mixer simultaneously. The variable-diameter spiral static mixer has built-in continuously variable diameter spiral guide vanes and no additional shearing structure, relying on the fluid's own motion to achieve deep mixing.

5. The method for online dilution and proportioning control of cosmetic raw materials according to claim 1, characterized in that, The specific steps of the three-stage final dilution and maturation of the plug flow are as follows: The remaining main dilution medium is used as the tertiary dilution medium and is injected into the feed end of the plug flow pipeline mixer simultaneously with the secondary deep dilution material and the compatibility auxiliary materials. The push-flow pipeline mixer adopts a straight pipe design without built-in mixing components, and achieves low-temperature maturation of the system by controlling the pipeline length to adjust the material residence time.

6. The method for online dilution and proportioning control of cosmetic raw materials according to claim 1, characterized in that, The three-way flow distribution of the main dilution medium satisfies the following mathematical relationship: Q1 + Q2 + Q3 = Q0 Q1 = k1 × Q0 Q2 = k2 × Q0 Q3 = k3 × Q0 Wherein, Q0 represents the total flow rate of the main dilution medium, Q1 represents the flow rate of the primary dilution medium, Q2 represents the flow rate of the secondary dilution medium, Q3 represents the flow rate of the tertiary dilution medium, k1 represents the diversion ratio coefficient of the primary dilution medium, ranging from 0.05 to 0.10, k2 represents the diversion ratio coefficient of the secondary dilution medium, ranging from 0.15 to 0.25, and k3 represents the diversion ratio coefficient of the tertiary dilution medium, ranging from 0.65 to 0.80, and k1+k2+k3=1. The diversion ratio coefficients are dynamically fine-tuned based on the final target concentration and the online detection results.

7. The method for online dilution and proportioning control of cosmetic raw materials according to claim 1, characterized in that, The online detection unit employs a surface-enhanced Raman scattering detection unit, with a built-in noble metal nanoarray reinforcement substrate targeting the component; The online detection unit acquires real-time Raman spectral data and establishes a multi-component quantitative model of the corresponding formulation through chemometrics algorithms to eliminate matrix signal interference and achieve specific quantitative detection of single components. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the primary pre-dilution outlet, adjusting the metering pump feed parameters of the first main dilution medium and the high-concentration thermosensitive functional mother liquor, and correcting the concentration deviation in the primary pre-dilution stage. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the secondary deep dilution outlet, adjusts the feed parameters of the metering pump for the second main dilution medium, and corrects the concentration deviation in the secondary deep dilution stage. The central control system performs feedback control based on the actual concentration data collected by the online detection unit at the three-stage final dilution outlet, adjusting the metering pump feed parameters of the high-concentration heat-sensitive efficacy mother liquor and compatibility excipients; When the central control system detects that the material concentration exceeds the preset qualified threshold, it switches the unqualified material to a dedicated recovery tank through a three-way reversing valve, and at the same time triggers the fault diagnosis program to automatically adjust the operating parameters.

8. The method for online dilution and proportioning control of cosmetic raw materials according to claim 7, characterized in that, The central control system incorporates a multivariable decoupled model predictive control algorithm for the three-stage gradient dilution process, establishes dynamic input-output models for each dilution unit, and decouples the coupling relationships between process parameters. The online detection unit is equipped with an automatic calibration device that performs baseline calibration periodically.

9. The method for online dilution and proportioning control of cosmetic raw materials according to claim 1, characterized in that, It also includes online cleaning, sterilization, and production changeover control steps, as detailed below: After production is completed, the central control system automatically executes online cleaning and online sterilization procedures; When switching formulas, the central control system first automatically executes the online cleaning and online sterilization programs, and then calls the preset formula parameters to complete the parameter update and trial production verification in sequence. The online cleaning program employs a turbulent cleaning mode, sequentially using purified water, alkaline cleaning solution, purified water, acidic cleaning solution, and purified water for cyclic cleaning. The online sterilization program employs saturated steam sterilization.

10. An online dilution and proportioning control system for cosmetic raw materials, characterized in that, The device includes a memory, a host computer, and a computer program stored in the memory and executable on the host computer, the computer program being configured to implement the steps of an online dilution and proportioning control method for cosmetic raw materials as described in any one of claims 1 to 9.

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