A method for preparing a ceramide cell phospholipid composition by complex coacervation and its application

Abstract

The present invention provides a method for preparing a ceramide cell phospholipid composition by complex coacervation and its application, belonging to the technical field of cosmetics. It solves the technical problems such as low preparation efficiency, high production energy consumption, poor preservation effect, poor moisturizing and whitening and anti-wrinkle effects of existing cosmetics. The formula of the ceramide cell phospholipid composition prepared by complex coacervation in the present invention is reasonable, with a high ceramide content, good product quality, can be stored for a long time, has the effects of promoting the absorption of active substances and reducing skin irritation, can significantly increase the water content of the skin, has a stable and lasting moisturizing effect, has soothing and repairing effects, and enhances the whitening and anti-aging effects; the method for preparing the ceramide cell phospholipid composition by complex coacervation in the present invention is produced by a combined device, and the hot cycle and pipeline production are adopted to ensure the mixing reaction effect, with high preparation efficiency, short production time and low energy consumption.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics, and relates to a ceramide cell phospholipid composition, in particular to a method for preparing a ceramide cell phospholipid composition by complex coacervation and its application. Background Art

[0002] Ceramide, as the main component of the intercellular lipid in the stratum corneum of the skin, is covalently bonded to fatty acids by an amide bond through long-chain sphingosine, plays an important role in the formation process of the epidermal stratum corneum, and has functions such as maintaining the skin barrier, moisturizing, anti-aging and disease treatment. Specifically, it can maintain the water-oil balance of the skin and enhance the self-protection of the skin; it can quickly penetrate into the skin and combine with the water in the stratum corneum to form a network structure to lock in moisture; ceramide can condition the skin and repair the skin barrier.

[0003] Therefore, ceramide, as an effective skin care active ingredient, is widely used in different cosmetics. However, in practical applications, ceramide is a highly crystalline substance with general oil solubility, poor applicability in formulations, and low skin retention. In order to improve the solubility of ceramide, improve its water dispersibility and transdermal permeability, existing technologies have adopted methods such as ceramide liposomes, ceramide vesicle dispersions and ceramide nanoemulsions to prepare ceramide nano-compositions, and their solubility and water dispersibility have been greatly improved. The content is generally 0.5%, or even 0.05%, and the content of the active ingredient is still very low, and the skin care effect is limited. Secondly, the prepared composite ceramide liposomes have large particle sizes, which hinder the transdermal absorption of ceramide; in addition, there is also a method of using high-pressure homogenization to prepare ceramide nanoemulsions. Through the treatment of a high-pressure homogenizer, a ceramide nanoemulsion with a semi-transparent or transparent appearance is obtained. This preparation has the characteristics of high stability, good water dispersibility and good biocompatibility, but requires more raw materials, a relatively complex preparation process and specific machines during the preparation process.

[0004] Complex coacervation is a type of phase separation method. It is a method in which two polymer wall materials form a complex coacervation phase due to electrostatic interaction by changing the external environment, such as dilution or pH adjustment, under appropriate conditions, and deposit on the surface of the core emulsion droplets to form microcapsules.

[0005] However, the existing equipment using the complex coacervation method has low production and preparation efficiency, high production cost and high energy consumption. After retrieval, for example, a Chinese patent document discloses a ceramide for skin moisturization and its preparation method [Application No.: CN201810568899.5; Publication No.: CN108478466B]. This ceramide for skin moisturization and its preparation method, the ceramide for skin moisturization is prepared from raw materials including konjac ceramide, rice ceramide, and rice bran ceramide. The ceramide for skin moisturization of the present invention is rich in konjac ceramide, rice ceramide, and rice bran ceramide. Although the ceramide for skin moisturization disclosed in this patent has certain effects such as whitening and moisturizing, etc., the component types of this patent are too single. Ceramide is a highly crystalline substance with general oil solubility, poor applicability in the formula, and low skin retention. Therefore, multiple principles need to be combined with each other to achieve better effects.

[0006] At the same time, for the ceramide nanoemulsion prepared by the prior art, the ceramide content is low and it is difficult for the skin to absorb. For example, although Chinese invention patent CN104546516A adopts the nano-liposome technology, the content of ceramide VI in the prepared composite ceramide liposome is 0.1% - 0.5%, and the content of ceramide IIIB is 0.1% - 0.6%.

[0007] Based on this, we propose a method and application for preparing a ceramide cytophospholipid composition by complex coacervation. By adopting thermal cycling and pipeline production preparation to ensure the mixing reaction effect, the preparation efficiency is high and the energy consumption is low; the prepared composition uses oppositely charged cytophospholipids and sodium alginate to form a composite wall material by complex coacervation, and then encapsulates ceramide. Through the skin-friendly effect of cytophospholipids, the transdermal absorption of ceramide is improved and the irritation is reduced; the prepared composition has a high ceramide content, stable appearance, and has the effects of moisturizing and whitening and anti-wrinkle. Summary of the Invention

[0008] The object of the present invention is to address the above problems existing in the prior art and propose a method and application for preparing a ceramide cytophospholipid composition by complex coacervation. The technical problem to be solved by this invention is: how to achieve a high ceramide content in the prepared cosmetic composition, with the effects of moisturizing and whitening and anti-wrinkle, and at the same time, the preparation efficiency is high and the energy consumption is low.

[0009] The object of the present invention can be achieved by the following technical solutions:

[0010] A method for preparing a ceramide cytophospholipid composition by complex coacervation, comprising the following preparation steps:

[0011] Step 1: Weigh a certain amount of cell phospholipids and sodium alginate respectively, and stir them in water at 35 - 60 °C to dissolve them fully to obtain a wall material solution; the weight of cell phospholipids and sodium alginate in the wall material solution accounts for 5% of the total weight, that is, the weight ratio of cell phospholipids and sodium alginate to the weight of cell phospholipids, sodium alginate and water is 1:20, and the weight ratio of cell phospholipids to sodium alginate is 1 - 5:1;

[0012] Step 2: Weigh a certain amount of ceramide, stir and dissolve it in a certain amount of oil, and add a certain amount of emulsifier while stirring to obtain an oil phase;

[0013] Step 3: Add the oil phase prepared in Step 2 to the wall material solution prepared in Step 1, and disperse it at high speed to obtain a uniform O / W type emulsion;

[0014] Step 4: Keep the O / W type emulsion prepared in Step 3 at 45 °C and stir it at a constant temperature. The constant temperature stirring speed is 20 - 550 r / min, adjust the pH to 3.8 - 6.8 with a 10% acid solution, and react for 10 - 30 minutes to obtain an emulsion;

[0015] Step 5: Cool the emulsion to 10 - 15 °C, the cooling time is 0.5 - 1 h, and adjust the pH to 6.0;

[0016] Step 6: Add transglutaminase to the emulsion, and solidify it at room temperature for 3.5 - 6.5 h to obtain a solidified composition.

[0017] The cell phospholipids are positively charged and the sodium alginate is negatively charged. The cell phospholipids and sodium alginate undergo charge neutralization and complex coacervation reaction.

[0018] The hydrophilic group of the cell phospholipids contains a branched structure, and its chemical formula is as follows:

[0019]

[0020] In the chemical formula, R1, R2 and R3 are each independently selected from: H, C1 - C4 alkyl groups and C3 - C4 cycloalkyl groups, and its hydrophobic group contains: C5 - 30 fatty chain structures.

[0021] The O / W type emulsion is an inclusion solution formed by the oil phase being wrapped inside the wall material.

[0022] The oil in Step 2 is one or more of soybean oil, octyldodecanol, isononyl isononanoate, camellia oil, olive oil, sweet almond oil, avocado oil or wheat germ oil. The weight ratio of ceramide to oil is 1:2, and the weight ratio of the oil to the total weight of the O / W type emulsion is 0.5 - 5%.

[0023] The emulsifier in the second step is one or several of Tween 80, polyglycerol esters, sucrose fatty acid esters, alkyl glycosides, hydrogenated lecithin, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene ethers, fatty acid polyoxyethylene esters or polyethers. The emulsifier accounts for 5-20% of the total weight of the O / W type emulsion.

[0024] The enzyme activity of the transglutaminase in the fifth step is 100 U / g, and the added weight of the transglutaminase is 1 / 3 - 1 / 12 of the total amount of the wall material solution. The acid solution in the fourth step is hydrochloric acid solution, acetic acid solution or sulfuric acid solution.

[0025] The stirring in water at 35 - 60°C in the first step, the constant temperature stirring in the fourth step, and the cooling in the fifth step are all under water bath conditions.

[0026] The composition is applied to the human skin alone or after being mixed with other cosmetics in a certain proportion.

[0027] It also includes a temperature control box and a heat exchange compression pump. The outer wall of the temperature control box is provided with a heat insulation layer, and several heat insulation plates are arranged inside the temperature control box. The several heat insulation plates divide the interior of the temperature control box into several heat preservation chambers. Sealing rubber rings are arranged at both the upper and lower ends of the heat preservation chambers. A high-speed dispersion assembly is arranged outside the third heat preservation chamber, and a high-speed dispersion tank is arranged inside the third heat preservation chamber. Stirring mechanisms are arranged inside the remaining heat preservation chambers. The heat exchange compression pump is located outside the fifth heat preservation chamber. Liquid injection pumps are connected between the first and second stirring mechanisms and the high-speed dispersion tank, between the high-speed dispersion tank and the third stirring mechanism, between the third stirring mechanism and the fourth stirring mechanism, and between the fourth stirring mechanism and the fifth stirring mechanism respectively. The heat exchange compression pump is connected to the heat preservation chambers through heat preservation pipes.

[0028] With the above structure, start the heat exchange compression pump, and control the water bath temperatures inside the first and sixth heat preservation chambers to be 35 - 60°C, 35 - 60°C, 40 - 50°C, 45°C, 10 - 15°C and 25°C respectively;

[0029] Weigh a certain amount of cell phospholipids, sodium alginate and water respectively, and inject them into the stirring mechanism inside the first heat preservation chamber, and stir in a water bath at 35 - 60°C to fully dissolve them to obtain a wall material solution;

[0030] Weigh a certain amount of ceramide, oil and emulsifier respectively, and inject them into the stirring mechanism inside the second heat preservation chamber, and stir fully in a water bath at 35 - 60°C to obtain an oil phase;

[0031] Through the liquid injection pump, inject the oil phase and the wall material solution into the high-speed dispersion tank inside the third heat preservation chamber, and in a water bath at 40 - 50°C, the high-speed dispersion assembly and the high-speed dispersion tank cooperate to carry out high-speed dispersion to obtain a uniform O / W type emulsion;

[0032] Inject the O / W emulsion into the stirring mechanism inside the fourth heat preservation chamber through an injection pump, and carry out constant-temperature stirring in a water bath at 45°C. The speed of constant-temperature stirring is 20 - 550 r / min. Then inject a 10% acid solution, adjust the pH to 3.8 - 6.8, and react for 10 - 30 minutes to obtain an emulsion.

[0033] Inject the emulsion into the stirring mechanism inside the fifth heat preservation chamber through an injection pump, and carry out cooling in a water bath at 10 - 15°C. The cooling time is 0.5 - 1 h, and adjust the pH to 6.0.

[0034] Inject the cooled emulsion into the stirring mechanism inside the sixth heat preservation chamber through an injection pump, and add transglutaminase to the emulsion. Cure it in a water bath at 25°C (at room temperature) for 3.5 - 6.5 h to obtain a cured composition.

[0035] Inside the inner four walls of the heat preservation chamber, annular heat exchange tubes are provided. The compressed gaseous refrigerant end of the heat exchange compression pump is connected to a multi-way control valve. The multi-way control valve is respectively connected to the inlet ends of the annular heat exchange tubes of the first four heat preservation chambers and the last heat preservation chamber through heat-insulating pipelines. The outlet ends of the annular heat exchange tubes of the first four heat preservation chambers and the last heat preservation chamber are connected to the inlet end of the annular heat exchange tube of the fifth heat preservation chamber through heat-insulating pipelines. The outlet end of the annular heat exchange tube of the fifth heat preservation chamber is connected to the gaseous refrigerant end of the heat exchange compression pump through a heat-insulating pipeline.

[0036] With the above structure, the heat exchange compression pump injects the compressed gaseous refrigerant into the multi-way control valve through the compressed gaseous refrigerant end, and then injects it into the inlet ends of the annular heat exchange tubes of the first four heat preservation chambers and the last heat preservation chamber through the multi-way control valve. The gaseous refrigerant condenses to form a liquid refrigerant, releasing heat to control the internal water temperature of the first four heat preservation chambers and the last heat preservation chamber. The liquid refrigerant enters the inlet end of the annular heat exchange tube of the fifth heat preservation chamber, and the liquid refrigerant evaporates and absorbs heat to control the internal water temperature of the fifth heat preservation chamber at 10 - 15°C.

[0037] On each heat preservation chamber, an injection pipe and a drain pipe are provided. The injection pipe is located above the drain pipe. On each heat preservation chamber, a first temperature sensor and a second temperature sensor are provided. The first temperature sensor extends into the interior of the heat preservation chamber, and the second temperature sensor extends into the interior of the corresponding stirring mechanism and high-speed dispersion tank.

[0038] With the above structure, the injection pipe is used for injecting water, and the drain pipe is used for draining water. The two cooperate to facilitate water replacement. The first temperature sensor monitors the water bath temperature inside each heat preservation chamber, and the second temperature sensor monitors the temperature inside the corresponding stirring mechanism and high-speed dispersion tank to ensure accurate temperature.

[0039] The stirring mechanism includes a stirring tank body. A number of uniformly distributed support legs are provided at the lower end of the stirring tank body. First sealing rings are provided on both the upper and lower parts of the outer wall of the stirring tank body. The first sealing rings cooperate with the sealing rubber rings at the corresponding positions of the heat preservation chamber for sealing. A tank cover is provided at the upper end of the stirring tank body. An exhaust pipe and a number of liquid injection connecting pipes are provided on the tank cover. An installation frame is fixed on the tank cover. A stirring frame is rotatably provided on the installation frame. The stirring frame is located inside the stirring tank body. A stirring motor is fixed on the installation frame. The output shaft of the stirring motor is in transmission connection with the rotating shaft of the stirring frame. An outlet pipe is provided at the lower end of the stirring tank body.

[0040] With the above structure, the first sealing rings cooperate with the sealing rubber rings at the corresponding positions of the heat preservation chamber for sealing to ensure sealing. The liquid injection connecting pipes are used to inject raw materials and the mixture during the process. The output shaft of the stirring motor drives the rotating shaft of the stirring frame to rotate. The stirring frame stirs the raw materials and the materials during the process for effective mixing and stirring to avoid precipitation, and then discharges from the outlet pipe. The exhaust pipe is used to discharge steam to ensure stable air pressure. The exhaust pipe can be connected with a conduit to extend into the water bath inside the heat preservation chamber to ensure stable temperature and more energy saving.

[0041] The high-speed dispersion tank includes a dispersion tank body. Second sealing rings are provided on both the upper and lower parts of the outer wall of the dispersion tank body. The second sealing rings cooperate with the sealing rubber rings at the corresponding positions of the heat preservation chamber for sealing. A drain valve is provided at the lower end of the dispersion tank body.

[0042] With the above structure, the second sealing rings cooperate with the sealing rubber rings at the corresponding positions of the heat preservation chamber for sealing to ensure sealing. The drain valve is used to discharge the mixture inside.

[0043] The high-speed dispersion assembly includes a base. An electric control box and a support are fixed at the upper end of the base. A rotating shaft is rotatably provided on the support. A driving gear is fixed in the middle of the rotating shaft. A lifting motor is fixed on the support. The output shaft of the lifting motor is in transmission connection with the rotating shaft. A lifting slide carriage is slidably provided on the support. A lifting rack is fixed on the lifting slide carriage. The lifting rack meshes with the driving gear. A fixing plate is fixed at the upper end of the lifting slide carriage. A stirring motor is fixed at the lower end of the fixing plate. A stirring shaft is fixed on the output shaft of the stirring motor. A stirring wheel is fixed at the end of the stirring shaft.

[0044] With the above structure, the output shaft of the lifting motor drives the rotating shaft to rotate, thereby driving the driving gear to rotate. The lifting rack meshes with the driving gear. The lifting rack drives the lifting slide carriage to slide up and down on the support, thereby driving the fixing plate to move up and down. The output shaft of the stirring motor drives the stirring shaft to rotate, thereby driving the stirring wheel to rotate at high speed. While the stirring wheel rotates at high speed, it can move up and down to ensure sufficient stirring and mixing.

[0045] A ceramide cell phospholipid composition is mainly made from raw materials in the following parts by weight: 1 - 5 parts of ceramide, 1 - 5 parts of cell phospholipid, 1 - 5 parts of sodium alginate, 1 - 5 parts of oil, 5 - 15 parts of emulsifier, 1 - 2 parts of acid solution, 0.3 - 1 part of transglutaminase, and 80 - 85 parts of water.

[0046] The sodium alginate is an equivalent substance to trehalose or the extract of Laminaria digitata.

[0047] An application of preparing a ceramide cell phospholipid composition by complex coacervation method, wherein the ceramide cell phospholipid composition is applied to the human skin alone or mixed with other cosmetics in a certain proportion.

[0048] Compared with the prior art, the method and application of preparing the ceramide cell phospholipid composition by complex coacervation method have the following advantages:

[0049] The ceramide cell phospholipid composition prepared by the present invention has a reasonable formula, a high ceramide content, good product quality, can be stored for a long time, has the functions of promoting the absorption of active substances, reducing skin irritation, can significantly increase the skin water content, has a stable and lasting moisturizing effect, has soothing and repairing effects, and enhances the whitening and anti - aging effects.

[0050] In the method of preparing the ceramide cell phospholipid composition by complex coacervation method in the present invention, a combined device is adopted, and heat circulation and pipeline - type production are used to ensure the mixing reaction effect, with high preparation efficiency, short production time and low energy consumption.

[0051] In the present invention, through the cooperation of a temperature control box, several stirring mechanisms and a high - speed dispersion tank, effective water - bath temperature control can be carried out. The heat exchange compression pump cooperates with the annular heat exchange pipe inside the heat preservation chamber to form a heat exchange cycle, which can effectively carry out constant temperature control, with high efficiency and good effect; by using several independent stirring mechanisms and a high - speed dispersion tank in cooperation, the temperature control of the mixture can be quickly achieved, with high reaction efficiency, fast stirring speed, no waiting time, improving timeliness, and forming a pipeline operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 is the preparation process block diagram of the present invention.

[0053] Figure 2 is the left - hand three - dimensional structure schematic diagram of some equipment in the present invention.

[0054] Figure 3 is the right - hand three - dimensional structure schematic diagram of some equipment in the present invention.

[0055] Figure 4 is the heat exchange cycle process block diagram of the present invention.

[0056] Figure 5 It is a three-dimensional structure schematic diagram of the stirring mechanism in the present invention.

[0057] Figure 6 It is a three-dimensional structure schematic diagram of the high-speed dispersion mechanism in the present invention.

[0058] Figure 7 It is a three-dimensional structure schematic diagram of some components of the high-speed dispersion mechanism in the present invention.

[0059] Figure 8 It is a diagram of the appearance state of the composition in Example 4 of the present invention.

[0060] Figure 9 It is a diagram of the appearance state of the composition in Example 5 of the present invention.

[0061] Figure 10 It is a diagram of the appearance state of the composition in Comparative Example 1 of the present invention.

[0062] Figure 11 It is a diagram of the appearance state of the composition in Comparative Example 2 of the present invention.

[0063] Figure 12 It is a statistical chart of the moisture retention performance test in the present invention.

[0064] Figure 13 It is a statistical chart of the lactic acid stimulation score results in the present invention.

[0065] Figure 14 It is a statistical chart of the test results of the red pigment content in the present invention.

[0066] Figure 15 It is a statistical chart of the TEWL value test results in the present invention.

[0067] Figure 16 It is a concentration-peak area curve graph in the present invention.

[0068] Figure 17 It is a graph of the cumulative penetration amount results in the present invention.

[0069] Figure 18 It is a graph of the diffusion percentage results in the present invention.

[0070] Figure 19 It is a graph of the penetration rate of glabridin in Group 1# of the present invention.

[0071] Figure 20 It is a graph of the penetration rate of glabridin in Group 2# of the present invention.

[0072] Figure 21 It is a SEw-skin wrinkle graph in the present invention.

[0073] Figure 22 It is a graph of the skin brightness L* value in the present invention.

[0074] Figure 23 These are the graphs of skin elasticity R2 value and R5 value in the present invention.

[0075] In the figure: 1. Temperature control box; 2. Stirring mechanism; 3. High-speed dispersion tank; 4. High-speed dispersion assembly; 5. Heat exchange compression pump; 6. First temperature sensor; 7. Second temperature sensor; 8. Sealing rubber ring; 9. Liquid injection pipe; 10. Drain pipe; 11. Liquid injection pump; 12. Stirring tank body; 13. Mounting rack; 14. Liquid injection connection pipe; 15. Stirring motor; 16. Exhaust pipe; 17. Tank cover; 18. Support leg; 19. Dispersion tank body; 20. Drain valve; 21. Base; 22. Electric control box; 23. Bracket; 24. Lifting motor; 25. Rotating shaft; 26. Lifting sliding frame; 27. Fixed plate; 28. Lifting rack; 29. Stirring motor; 30. Stirring shaft; 31. Stirring wheel; 32. First sealing ring; 33. Second sealing ring; 34. Heat exchange pipe. Specific embodiments

[0076] The following are specific embodiments of the present invention in combination with the accompanying drawings to further describe the technical solutions of the present invention, but the present invention is not limited to these embodiments.

[0077] As Figures 1 - 6 shown, the method for preparing a ceramide cell phospholipid composition by the complex coacervation method includes the following preparation steps:

[0078] Step 1: Weigh a certain amount of cell phospholipids and sodium alginate respectively, and stir them in water at 35 - 60 °C until fully dissolved to obtain a wall material solution; in the wall material solution, the weight of cell phospholipids and sodium alginate accounts for 5% of the total weight, that is, the weight ratio of cell phospholipids and sodium alginate to the weight of cell phospholipids, sodium alginate and water is 1:20, and the weight ratio of cell phospholipids to sodium alginate is 1 - 5:1;

[0079] Step 2: Weigh a certain amount of ceramide, stir and dissolve it in a certain amount of oil, and add a certain amount of emulsifier while stirring to obtain an oil phase;

[0080] Step 3: Add the oil phase prepared in Step 2 to the wall material solution prepared in Step 1, and disperse it at high speed to obtain a uniform O / W type emulsion;

[0081] Step 4: Keep the O / W type emulsion prepared in Step 3 at 45 °C for constant temperature stirring, the speed of constant temperature stirring is 20 - 550 r / min, adjust the pH to 3.8 - 6.8 with a 10% acid solution, and react for 10 - 30 minutes (preferably 20 minutes) to obtain an emulsion;

[0082] Step 5: Cool the emulsion to 10 - 15 °C for 0.5 - 1 h, and adjust the pH to 6.0;

[0083] Step 6: Add transglutaminase to the emulsion and cure it at room temperature for 3.5 - 6.5 h to obtain a cured composition.

[0084] The cell phospholipids are positively charged and sodium alginate is negatively charged. The cell phospholipids and sodium alginate undergo charge neutralization to cause a coacervation reaction.

[0085] The hydrophilic group of the cell phospholipids contains a branched-chain structure, and its chemical formula is as follows:

[0086]

[0087] In the chemical formula, R1, R2, and R3 are each independently selected from: H, C1 - C4 alkyl groups, and C3 - C4 cycloalkyl groups, and its hydrophobic group contains: a C5 - 30 aliphatic chain structure.

[0088] The O / W type emulsion is an inclusion solution formed by the oil phase being wrapped inside the wall material.

[0089] The oil in Step 2 is one or more of soybean oil, octyldodecanol, isononyl isononanoate, camellia oil, olive oil, sweet almond oil, avocado oil, or wheat germ oil. The weight ratio of ceramide to oil is 1:2, and the weight ratio of the oil to the total weight of the O / W type emulsion is 0.5 - 5%.

[0090] The emulsifier in Step 2 is one or more of Tween 80, polyglycerol esters, sucrose fatty acid esters, alkyl glycosides, hydrogenated lecithin, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene ethers, fatty acid polyoxyethylene esters, or polyethers. The emulsifier accounts for 5 - 20% of the total weight of the O / W type emulsion.

[0091] The enzyme activity of the transglutaminase in Step 5 is 100 U / g, and the added weight of the transglutaminase is 1 / 3 - 1 / 12 of the total amount of the wall material solution. The acid solution in Step 4 is hydrochloric acid solution, acetic acid solution, or sulfuric acid solution.

[0092] The stirring in 35 - 60 °C water in Step 1, the constant-temperature stirring in Step 4, and the cooling in Step 5 are all under water bath conditions.

[0093] The composition is applied to the human skin alone or mixed with other cosmetics in a certain proportion.

[0094] It also includes a temperature control box 1 and a heat exchange compression pump 5. The outer wall of the temperature control box 1 is provided with a heat insulation layer. Inside the temperature control box 1, there are several heat insulation plates which divide the interior of the temperature control box 1 into several heat preservation chambers. Sealing rubber rings 8 are provided at both the upper and lower ends of the heat preservation chambers. A high-speed dispersion assembly 4 is provided outside the third heat preservation chamber, and a high-speed dispersion tank 3 is provided inside the third heat preservation chamber. Stirring mechanisms 2 are provided inside the remaining heat preservation chambers. The heat exchange compression pump 5 is located outside the fifth heat preservation chamber. Liquid injection pumps 11 are connected between the first and second stirring mechanisms 2 and the high-speed dispersion tank 3, between the high-speed dispersion tank 3 and the third stirring mechanism 2, between the third stirring mechanism 2 and the fourth stirring mechanism 2, and between the fourth stirring mechanism 2 and the fifth stirring mechanism 2 respectively. The heat exchange compression pump 5 is connected to the heat preservation chambers through heat preservation pipelines;

[0095] Start the heat exchange compression pump 5, and control the water bath temperatures inside the first and sixth heat preservation chambers to be 35 - 60°C, 35 - 60°C, 40 - 50°C, 45°C, 10 - 15°C, and 25°C in sequence;

[0096] Weigh a certain amount of cell phospholipids, sodium alginate, and water respectively, and inject them into the stirring mechanism 2 inside the first heat preservation chamber. Stir them in a water bath at 35 - 60°C to fully dissolve, obtaining a wall material solution;

[0097] Weigh a certain amount of ceramide, oil, and emulsifier respectively, and inject them into the stirring mechanism 2 inside the second heat preservation chamber. Stir them fully in a water bath at 35 - 60°C to obtain an oil phase;

[0098] Through the liquid injection pump 11, inject the oil phase and the wall material solution into the high-speed dispersion tank 3 inside the third heat preservation chamber. In a water bath at 40 - 50°C, the high-speed dispersion assembly 4 and the high-speed dispersion tank 3 cooperate to perform high-speed dispersion, obtaining a uniform O / W type emulsion;

[0099] Through the liquid injection pump 11, inject the O / W type emulsion into the stirring mechanism 2 inside the fourth heat preservation chamber. In a water bath at 45°C, perform constant-temperature stirring at a speed of 20 - 550 r / min, then inject a 10% acid solution, adjust the pH to 3.8 - 6.8, and react for 10 - 30 minutes (preferably 20 minutes) to obtain an emulsion;

[0100] Through the liquid injection pump 11, inject the emulsion into the stirring mechanism 2 inside the fifth heat preservation chamber. In a water bath at 10 - 15°C, perform cooling for 0.5 - 1 h, and adjust the pH to 6.0;

[0101] Through the liquid injection pump 11, inject the cooled emulsion into the stirring mechanism 2 inside the sixth heat preservation chamber, and add transglutaminase to the emulsion. In a water bath at 25°C (at room temperature), cure for 3.5 - 6.5 h to obtain a cured composition.

[0102] On the inner sides of the inner four walls of the heat preservation chamber, annular heat exchange pipes 34 are provided. The compressed gaseous refrigerant end of the heat exchange compression pump 5 is connected with a multi-way control valve. The multi-way control valve is respectively connected with the annular heat exchange pipes 34 of the first four heat preservation chambers and the last heat preservation chamber through heat preservation pipelines at the inlet ends. The outlet ends of the annular heat exchange pipes 34 of the first four heat preservation chambers and the last heat preservation chamber are connected with the inlet end of the annular heat exchange pipe 34 of the fifth heat preservation chamber through heat preservation pipelines. The outlet end of the annular heat exchange pipe 34 of the fifth heat preservation chamber is connected with the gaseous refrigerant end of the heat exchange compression pump 5 through a heat preservation pipeline;

[0103] The heat exchange compression pump 5 injects the compressed gaseous refrigerant into the multi-way control valve through the compressed gaseous refrigerant end, and then injects it into the inlet ends of the annular heat exchange pipes 34 of the first four heat preservation chambers and the last heat preservation chamber through the multi-way control valve. The gaseous refrigerant condenses to form a liquid refrigerant, releasing heat to control the internal water temperature of the first four heat preservation chambers and the last heat preservation chamber. The liquid refrigerant enters the inlet end of the annular heat exchange pipe 34 of the fifth heat preservation chamber. The liquid refrigerant evaporates and absorbs heat to control the internal water temperature of the fifth heat preservation chamber to be 10 - 15 °C.

[0104] Liquid injection pipes 9 and drain pipes 10 are provided on the heat preservation chambers. The liquid injection pipes 9 are located above the drain pipes 10. First temperature sensors 6 and second temperature sensors 7 are provided on the heat preservation chambers. The first temperature sensors 6 extend into the interior of the heat preservation chambers, and the second temperature sensors 7 extend into the interiors of the corresponding stirring mechanisms 2 and high-speed dispersion tanks 3;

[0105] The liquid injection pipes 9 are used for injecting water, and the drain pipes 10 are used for draining water. The two cooperate to facilitate water replacement. The first temperature sensors 6 monitor the water bath temperature inside each heat preservation chamber, and the second temperature sensors 7 monitor the temperature inside the corresponding stirring mechanisms 2 and high-speed dispersion tanks 3 to ensure accurate temperature.

[0106] The stirring mechanism 2 includes a stirring tank body 12. A number of uniformly distributed support legs 18 are provided at the lower end of the stirring tank body 12. First sealing rings 32 are provided on the upper and lower outer walls of the stirring tank body 12. The first sealing rings 32 cooperate with the sealing rubber rings 8 at the corresponding positions of the heat preservation chamber for sealing. A tank cover 17 is provided at the upper end of the stirring tank body 12. An exhaust pipe 16 and a number of liquid injection connection pipes 14 are provided on the tank cover 17. An installation frame 13 is fixed on the tank cover 17. A stirring frame is rotatably provided on the installation frame 13. The stirring frame is located inside the stirring tank body 12. A stirring motor 15 is fixed on the installation frame 13. The output shaft of the stirring motor 15 is in transmission connection with the rotating shaft of the stirring frame. An outlet pipe is provided at the lower end of the stirring tank body 12;

[0107] The first sealing ring 32 cooperates with the sealing rubber ring 8 at the corresponding position of the heat preservation chamber to ensure sealing. The liquid injection connecting pipe 14 is used for injecting raw materials and the mixture during the process. The output shaft of the stirring motor 15 drives the rotating shaft of the stirring frame to rotate, and the stirring frame stirs the raw materials and the mixture during the process for effective mixing and agitation to avoid precipitation, and then discharges from the discharge pipe. The exhaust pipe 16 is used for discharging steam to ensure stable air pressure. The exhaust pipe 16 can be connected with a conduit to extend into the internal water bath of the heat preservation chamber to ensure stable temperature and more energy-saving.

[0108] The high-speed dispersion tank 3 includes a dispersion tank body 19. Second sealing rings 33 are provided on both the upper and lower parts of the outer wall of the dispersion tank body 19. The second sealing rings 33 cooperate with the sealing rubber rings 8 at the corresponding positions of the heat preservation chamber to ensure sealing. A drain valve 20 is provided at the lower end of the dispersion tank body 19;

[0109] The second sealing rings 33 cooperate with the sealing rubber rings 8 at the corresponding positions of the heat preservation chamber to ensure sealing. The drain valve 20 is used for discharging the mixture inside.

[0110] The high-speed dispersion assembly 4 includes a base 21. An electric control box 22 and a bracket 23 are fixed at the upper end of the base 21. A rotating shaft 25 is rotatably provided on the bracket 23. A driving gear is fixed in the middle of the rotating shaft 25. A lifting motor 24 is fixed on the bracket 23. The output shaft of the lifting motor 24 is in transmission connection with the rotating shaft 25. A lifting carriage 26 is slidably provided on the bracket 23. A lifting rack 28 is fixed on the lifting carriage 26. The lifting rack 28 meshes with the driving gear. A fixing plate 27 is fixed at the upper end of the lifting carriage 26. A stirring motor 29 is fixed at the lower end of the fixing plate 27. A stirring shaft 30 is fixed on the output shaft of the stirring motor 29. A stirring wheel 31 is fixed at the end of the stirring shaft 30;

[0111] The output shaft of the lifting motor 24 drives the rotating shaft 25 to rotate, thereby driving the driving gear to rotate. The lifting rack 28 meshes with the driving gear, and the lifting rack 28 drives the lifting carriage 26 to slide up and down on the bracket 23, thereby driving the fixing plate 27 to lift. The output shaft of the stirring motor 29 drives the stirring shaft 30 to rotate, thereby driving the stirring wheel 31 to rotate at high speed. While the stirring wheel 31 rotates at high speed, it can be lifted to ensure sufficient stirring and mixing.

[0112] By cooperating the temperature control box 1 with a number of stirring mechanisms 2 and the high-speed dispersion tank 3, effective water bath temperature control can be carried out. The heat exchange compression pump 5 cooperates with the internal annular heat exchange pipe 34 of the heat preservation chamber to form a heat exchange cycle, and effective constant temperature control can be carried out with high efficiency and good effect;

[0113] By adopting the cooperation of a number of independent stirring mechanisms 2 and the high-speed dispersion tank 3, the temperature control of the mixture can be quickly achieved, with high reaction efficiency, fast stirring speed, no waiting time, improved timeliness, and forming a pipeline operation.

[0114] A ceramide cell phospholipid composition is mainly made from raw materials in the following parts by weight: 1 - 5 parts of ceramide, 1 - 5 parts of cell phospholipid, 1 - 5 parts of sodium alginate, 1 - 5 parts of oil, 5 - 15 parts of emulsifier, 1 - 2 parts of acid solution, 0.3 - 1 part of transglutaminase, and 80 - 85 parts of water.

[0115] The sodium alginate and trehalose or the extract of Laminaria digitata are equivalent substances.

[0116] Example 1

[0117] This ceramide cell phospholipid composition is mainly made from raw materials in the following parts by weight: 1 part of ceramide, 1 part of cell phospholipid, 1 part of sodium alginate, 1 part of oil, 5 parts of emulsifier, 1 part of acid solution, 0.3 part of transglutaminase, and 80 parts of water.

[0118] The preparation steps of Example 1 are as follows:

[0119] Step 1: Weigh a certain amount of cell phospholipid, sodium alginate and water respectively, inject them into the stirring mechanism 2 inside the first heat preservation chamber, and stir them in a water bath at 35 - 60 °C until they are fully dissolved to obtain a wall material solution.

[0120] Step 2: Weigh a certain amount of ceramide, oil and emulsifier respectively, inject them into the stirring mechanism 2 inside the second heat preservation chamber, and stir them fully in a water bath at 35 - 60 °C to obtain an oil phase.

[0121] Step 3: Through the liquid injection pump 11, inject the oil phase prepared in Step 2 and the wall material solution prepared in Step 1 into the high - speed dispersion tank 3 inside the third heat preservation chamber. In a water bath at 40 - 50 °C, the high - speed dispersion assembly 4 and the high - speed dispersion tank 3 cooperate to carry out high - speed dispersion to obtain a uniform O / W type emulsion.

[0122] Step 4: Through the liquid injection pump 11, inject the O / W type emulsion into the stirring mechanism 2 inside the fourth heat preservation chamber. In a water bath at 45 °C, carry out constant - temperature stirring, and the speed of the constant - temperature stirring is 20 - 550 r / min. Then inject 10% acid solution to adjust the pH to 3.8 - 6.8, and react for 10 - 30 minutes to obtain an emulsion.

[0123] Step 5: Through the liquid injection pump 11, inject the emulsion into the stirring mechanism 2 inside the fifth heat preservation chamber. In a water bath at 10 - 15 °C, carry out cooling, and the cooling time is 0.5 - 1 h, and adjust the pH to 6.0.

[0124] Step 6: Through the liquid injection pump 11, inject the cooled emulsion into the stirring mechanism 2 inside the sixth heat preservation chamber, and add transglutaminase to the emulsion. In a water bath at 25 °C (at room temperature), solidify for 3.5 - 6.5 h to obtain a solidified composition.

[0125] Example 2

[0126] This ceramide cell phospholipid composition is mainly made from raw materials in the following parts by weight: 2 parts of ceramide, 2 parts of cell phospholipid, 2 parts of sodium alginate, 2 parts of oil, 10 parts of emulsifier, 1.5 parts of acid solution, 0.6 part of transglutaminase, and 83 parts of water.

[0127] The preparation method steps of Example 2 are the same as those of Example 1.

[0128] Example 3

[0129] This ceramide cell phospholipid composition is mainly made from raw materials in the following parts by weight: 5 parts of ceramide, 5 parts of cell phospholipid, 5 parts of sodium alginate, 5 parts of oil, 15 parts of emulsifier, 2 parts of acid solution, 1 part of transglutaminase, and 85 parts of water.

[0130] The preparation method steps of Example 3 are the same as those of Example 1.

[0131] Example 4

[0132] This ceramide cell phospholipid composition is mainly made from raw materials in the following parts by weight: 1 part of ceramide, 2 parts of cell phospholipid, 1 part of sodium alginate, 2 parts of oil, 10 parts of emulsifier, 2 parts of acid solution, 0.6 part of transglutaminase, and 83 parts of water.

[0133] The preparation method steps of Example 4 are the same as those of Example 1.

[0134] Example 5

[0135] Example 5 has the same raw materials in the same parts by weight as those of Example 4;

[0136] The preparation method steps of Example 5 are as follows: only two separate stirring tanks are used;

[0137] Step 1, Weigh a certain amount of cell phospholipid, sodium alginate, and water respectively, inject them into the first stirring tank, and stir at 35 - 60 °C to fully dissolve them to obtain a wall material solution;

[0138] Step 2, Weigh a certain amount of ceramide, oil, and emulsifier respectively, inject them into the second stirring tank, and fully stir at 35 - 60 °C to obtain an oil phase;

[0139] Step 3, Add the oil phase prepared in Step 2 into the first stirring tank and fully stir to obtain a homogeneous O / W type emulsion;

[0140] Step 4: Adjust the temperature of the first stirring kettle to 45°C, carry out constant-temperature stirring, the speed of the constant-temperature stirring is 20 - 550 r / min, adjust the pH to 3.8 - 6.8 with a 10% acid solution, and react for 10 - 30 minutes to obtain an emulsion;

[0141] Step 5: Adjust the temperature of the first stirring kettle to 10 - 15°C, cool the emulsion, the cooling time is 0.5 - 1 h, and adjust the pH to 6.0;

[0142] Step 6: Add transglutaminase to the first stirring kettle, and cure at room temperature for 3.5 - 6.5 h to obtain a cured composition.

[0143] Conduct a comparative experiment on the compositions prepared in Examples 1 - 5: Among them, the comparison criteria are: production efficiency and unit power consumption (energy consumption), the weight of each portion of the raw materials is the same, and the experimental table (as shown in Table 1):

[0144]

[0145] Table 1

[0146] As can be seen from Table 1, in Examples 1 - 4, through the combined device, using thermal cycling and pipeline production to ensure the mixing reaction effect, the preparation efficiency is high, the production time is short, and the energy consumption is low.

[0147] Take equal amounts of the cured products prepared in Examples 1 - 5, as well as two comparative examples, with the raw material ratios and observe the appearance states of the cured products after preparation (as shown in Table 2), and the weight of each portion is the same:

[0148]

[0149] Table 2

[0150] As can be seen from Table 2, the cured products prepared in Examples 1 - 5 are relatively transparent in appearance. For the cured products prepared in Comparative Examples 1 - 2, when only one kind of wall material is used alone, the complex coacervation reaction cannot occur to form a relatively stable inclusion, and the appearance is relatively turbid. For Example 4, see Appendix Figure 8 、For Example 5, see Appendix Figure 9 、For Comparative Example 1, see Appendix Figure 10 、For Comparative Example 2, see Appendix Figure 11 。

[0151] Take equal amounts of the cured products prepared in Examples 1 - 5 and the cured products prepared in Comparative Examples 1 - 2, and let them stand for a period of time, and observe the appearance states (as shown in Table 3):

[0152]

[0153] Table 3

[0154] As shown in Table 3, the solidified products prepared in Examples 1, 2, 4 and 5 are relatively transparent after one month at room temperature, Example 1 becomes turbid after one month at 45°C, Example 2 becomes turbid after one month at 45°C and 5°C, Example 3 becomes turbid (precipitate) due to a relatively high relative concentration, and the solidified products prepared in Comparative Examples 1 and 2 will precipitate after a period of time. Therefore, the formulas of Examples 4 and 5 are reasonable, and the effects are the best.

[0155] An application of preparing a ceramide cell phospholipid composition by a complex coacervation method, wherein the ceramide cell phospholipid composition is applied to human skin alone or after being mixed with other cosmetics in a certain proportion.

[0156] In order to prove the efficacy and penetration-promoting effect of the composition prepared by the present invention, the inclusions prepared in Example 4 were added to an eye cream containing HPR, and an efficacy test was performed. The eye cream formula is shown in Table 4:

[0157]

[0158] Table 4

[0159] A composition of ceramide, cellular phospholipids and sodium alginate prepared in Example 4, hereinafter referred to as the composition, was mixed with an eye cream containing HPR in a certain amount and tested.

[0160] (1) Conducting a composition basic repair and moisturizing test

[0161] Subjects: A total of 35 subjects, 5 males and 30 females, aged 22 to 49 years old, with an average age of 28.7±7.1 years old; all met the voluntary inclusion criteria. Five subjects were lost to follow-up (due to personal reasons), and the final number of subjects who completed the test was 30.

[0162] The main equipment and test indicators are shown in Table 5:

[0163] Name Detection Index Skin Melanin and Hematin Test Probe MX18 Erythrin Skin Moisture Loss Test Probe TM300 TEWL Value

[0164] Table 5

[0165] Test method:

[0166] 1) Moisturizing performance test

[0167] Test samples: matrix, composition, blank (not applicable to any sample); site: inner arm; number of people: 30 people; parameters: stratum corneum water content, transepidermal water loss TEWL; test conditions: temperature 20±1℃, humidity 50±10; time points: 0h, 1h, 2h, 4h, 6h;

[0168] 2) Fix performance test

[0169] The subjects continuously used the composition for 28 days. The usage method of the composition: After cleansing the face in the morning and evening, take an appropriate amount (about 0.3 g) and apply it to the face, using it at least twice a day. Self-control before and after was adopted, and the test time points were: D0, D14, and D28. After the subjects adapted to the environment at room temperature of 21 ± 1°C and relative humidity of 50 ± 10% for 20 minutes, the lactic acid stimulation score, redness, and TEWL value were detected, and each area was measured in parallel at least 3 times. The detection indexes are shown in Table 6 as follows:

[0170] Serial Number Inspection and Testing Items Inspection and Testing Sites Inspection and Testing Indexes 1 Lactic Acid Stimulation Test Face Lactic Acid Stimulation Score 2 Erythema Index Face Erythrin 3 Skin Moisture Loss Face TEWL Value

[0171] Table 6

[0172] Data processing and statistical analysis methods:

[0173] The statistical analysis of the data was carried out using statistical analysis software. All data were expressed as mean ± standard deviation If the requirements of normal distribution were met, paired t-tests were used for the comparison before and after self-control, otherwise, the sum test of two related samples was used.

[0174] Test results:

[0175] 1) Moisturizing

[0176] The statistical chart of the moisturizing performance test (as Figure 12 shown). In the short-term test, compared with the skin water content of 34.89 at 0 h before using the sample containing the composition, after use, the skin water content values at 1 h, 2 h, 4 h, and 6 h increased by 18.7%, 16.5%, 14.4%, and 12.5% respectively. From the test results of the water content of the skin stratum corneum, the skin water content was the highest at 1 h after using the sample and then gradually decreased, which was related to the fact that no cosmetics were applied to the skin during the test period and the skin moisture was lost; after using the facial mask for 6 h, the skin water content was still higher than that before using the composition, indicating that the composition could significantly increase the skin water content and had a stable and lasting water replenishing effect.

[0177] 2) Repair (The test results table of the repair and soothing effects of cosmetics is shown in Table 7 below):

[0178]

[0179] Note: P < 0.05 indicates significant difference; P > 0.05 indicates no significant difference.

[0180] Table 7

[0181] Specific test results:

[0182] 1) The statistical chart of the lactic acid stimulation score results (as Figure 13 shown), the differential analysis of the lactic acid stimulation score results ( n = 30); The subjects made semi-subjective evaluations, assisted by dermatologists, to obtain lactic acid stimulation scores. Compared with the initial values, the lactic acid stimulation scores showed a decreasing trend and there were significant differences after 28 days of using the composition (P < 0.05), indicating that the skin repair barrier was repaired.

[0183] 2) Statistical chart of the test results of the content of red pigment (as Figure 14 shown), analysis of the differences in the test results of the content of red pigment ( n = 30); The testers used instrument equipment to collect the content of red pigment on the faces of the subjects. Compared with the initial values, the content of red pigment showed a decreasing trend and there were significant differences after 28 days of using the composition (P < 0.05), indicating that the skin was soothed after using the composition.

[0184] 3) Statistical chart of the test results of TEWL value (as Figure 15 shown), analysis of the differences in the test results of TEWL value ( n = 30); The testers used instrument equipment to collect the TEWL value on the faces of the subjects. Compared with the initial values, the transepidermal water loss showed a decreasing trend and there were significant differences after 28 days of using the composition (P < 0.05), indicating that the skin barrier was repaired and the moisturizing ability was improved.

[0185] To sum up the above:

[0186] 1. After continuously using the test composition for 28 days, the lactic acid stimulation scores of the subjects were significantly lower than those before use, and the content of red pigment was significantly lower than that before use. Therefore, it can be considered that under the research conditions, this composition has a soothing effect.

[0187] 2. After continuously using the test composition for 28 days, the water content of the stratum corneum did not increase significantly compared with that before use, and the transepidermal water loss was significantly lower than that before use. Therefore, it can be considered that under the research conditions, this composition has a repairing effect.

[0188] (2) Conduct the penetration enhancement effect test of the composition

[0189] While using cell phospholipids and sodium alginate to form a composite wall material, ceramide was encapsulated to enable the three components to play a synergistic role, having functions such as skin barrier repair, intelligent moisturization, and promoting the absorption of active substances. The following are the data on promoting the penetration of the whitening ingredient glabridin and the anti-aging ingredient HPR.

[0190] 1. Determination of the transdermal penetration enhancement of the whitening efficacy ingredient glabridin

[0191] Materials: The back skin of piglets at 1 month old;

[0192] Equipment: TK-12D type drug transdermal absorption Franz diffusion cell, Shanghai Kaili Medical Technology Co., Ltd.; constant temperature magnetic stirrer;

[0193] Test sample table, Table 8 is as follows:

[0194]

[0195] Table 8

[0196] 1.1 Determination of the in vitro penetration ability of the active substance

[0197] (1) First, fix the skin between the supply chamber and the receiving chamber of the Franz diffusion cell, with the stratum corneum of the skin facing the supply chamber and the dermal layer facing the receiving chamber;

[0198] (2) Add 7.0 mL of the receiving solution to the receiving chamber. After tightening and fixing the skin of the suckling pig, add 1.5 mL of the receiving solution (PBS containing 30% methanol) to the receiving chamber through a sampler, exhaust the air, and make the dermal layer of the skin in close contact with the receiving solution;

[0199] (3) Add different samples to the skin surface in the supply chamber, and the effective penetration area S is approximately 3.14 cm2. Add 300 μL of the sample to the surface of the pig skin and spread the sample evenly from the center of the skin radially to the edge. Each sample has 3 replicates and parallels (the three replicates use the skin of specific parts of independent donors);

[0200] (4) Penetration: Turn on the electromagnetic stirrer and stir at a speed of 300 rpm, maintain a constant water bath at (32 ± 1) °C, and ensure that there are no bubbles in the water bath sandwich;

[0201] (5) Take the sample solutions at the time points of 1 h, 2 h, 4 h, 6 h, and 24 h respectively. Use a sampler to draw 2.0 mL of the receiving solution through a sampling tube, and then place it in a 2 mL EPP tube. In addition, an equal amount of the receiving solution is added after each sampling.

[0202] 1.2 Detection of the transdermal content

[0203] After 24 h of penetration, detect the content of the sample to be measured on the skin surface, in the skin, and under the skin at each time point for different experimental groups. The specific treatment methods are as follows:

[0204] Detection of the unpenetrated part on the skin surface: After 24 h, use a 1 mL pipette to suck methanol and blow and wash the skin surface repeatedly for 5 times, a total of 5 mL, and place it in a 5 mL EPP tube for testing.

[0205] Detection of the part inside the skin: Use a sterilized scalpel to cut the skin along the inner edge of the supply chamber, cut the skin into pieces, add 5 mL of methanol, and extract it by ultrasound for 60 min. After the ultrasound is completed, suck out the supernatant for testing;

[0206] Subcutaneous part detection: At each time point, 2.0 mL of receiving solution drawn from the receiving chamber was placed in a 2 mL EP tube for testing.

[0207] Chromatographic conditions (glabridin)

[0208] HPLC parameter table, Table 9 is as follows:

[0209]

[0210] Table 9

[0211] A standard curve was drawn with concentration as the X-axis and peak area as the Y-axis, and the standard curve equation was obtained: y=45668.5x+36023.2, r2=0.99996.

[0212] The concentration-peak area table, Table 10, is as follows:

[0213] Concentration Point Number Concentration (μg / mL) Peak Area S1 0 0 S2 0.16 7644 S3 0.8 38038 S4 4 192971 S5 20 955975 S6 100 4714544 S7 500 22847923

[0214] Table 10

[0215] Concentration-peak area curve (such as Figure 16 The cumulative penetration results are as follows:

[0216] The cumulative penetration amount Q is calculated as follows: Q = Cn × V + ∑Ci × V0 (i = 1···n-1)

[0217] Note: Q: cumulative permeation volume; V: volume of receiving solution in the receiving chamber; V0: volume of each sampling; Ci: drug concentration in the receiving solution from the first sampling to the last sampling; Cn: sample concentration measured at the nth sampling point, as shown in Table 11:

[0218]

[0219] Table 11

[0220] Note: Q in the figure is the cumulative skin penetration at 24h (μg), and SD is the standard deviation.

[0221] Cumulative penetration results (such as Figure 17 shown), by Figure 17 It can be seen that after 24 hours of surface exposure, the cumulative permeation amount of glabridin in group 1# (0.5% glabridin without the composition) was 8.392 μg, and the cumulative permeation amount of glabridin in group 2# (0.5% glabridin added to the composition) was 41.480 μg; the addition of the composition had a penetration-promoting effect on glabridin.

[0222] Diffusion percentage P = Q / Po*100%; Note: Q is the cumulative permeation amount of the sample in the receiving chamber at each time point / Po is the theoretical content of the sample in the release pool.

[0223] Time - Permeability Table, Table 12 is as follows:

[0224]

[0225] Table 12

[0226] Diffusion percentage result graph (as Figure 18 shown), after 24 - hour surface exposure, the diffusion percentage of glabridin in Group 1# (0.5% glabridin without the composition) is 0.583%, and the diffusion percentage of glabridin in Group 2# (0.5% glabridin with the composition) is 52.113%; the diffusion percentage has increased significantly.

[0227] Permeation coefficient result:

[0228] Permeation coefficient: A regression equation is made with the cumulative permeation amount against the permeation time, and the slope of the equation is the permeation coefficient Kp (i.e., the permeation rate). Table 13 is as follows:

[0229]

[0230] Table 13

[0231] The permeation rate of glabridin in Group 1# is 0.388 μg / h, as Figure 19 shown:

[0232] The permeation rate of glabridin in Group 2# is 30.491 μg / h, as Figure 20 shown;

[0233] Combined with the results of the cumulative permeation amount and the permeation rate, it can be seen that the permeability of 0.5% glabridin with the composition is better than that without the composition.

[0234] 2. HPR Transdermal

[0235] Hydroxypinacolone retinoate, abbreviated as HPR, belongs to the retinoid family. Hydroxypinacolone retinoate (HPR) is a retinoid derivative modified with hydroxypinacolone, which can directly bind to cellular retinoic acid receptors (RARs), can regulate the metabolism of the epidermis and stratum corneum, has anti - aging effects, can reduce sebum overflow, fade epidermal pigments, and play roles in preventing skin aging, treating acne, and lightening and fading spots. Two groups of eye creams both added with HPR were tested, one group added the composition and the other group did not. The transdermal effects of the two groups of samples were tested, and volunteers applied them for 8 weeks.

[0236] Number of testers: 30 people. The main test equipment is shown in Table 14:

[0237]

[0238] Table 14

[0239] Test conditions: temperature 21 ± 1°C, humidity 50 ± 10%

[0240] Test method: Apply around the eyes

[0241] Test time: The subjects used the anti-wrinkle eye cream once in the morning and once in the evening every day. A self-control before and after was adopted, and the test was conducted in the eighth week.

[0242] Data processing and statistical analysis method:

[0243] Statistical analysis of the data was performed using statistical analysis software. If the requirements of normal distribution were met, paired t-tests were used for the comparison before and after by itself; otherwise, the Wilcoxon signed-rank test for two related samples was used.

[0244] SEw - Skin wrinkle diagram (as Figure 21 shown), it can be seen from Figure 21 that when using the anti-wrinkle eye cream containing composition HPR, the SEw - skin wrinkles continued to decline. Therefore, adding the composition while using the anti-wrinkle eye cream containing HPR can promote the absorption of HPR, further reduce the SEw - skin wrinkle value, and has an anti-wrinkle effect.

[0245] Skin brightness L* value (as Figure 22 shown), it can be seen from Figure 22 that when using the anti-wrinkle eye cream containing composition HPR and comparing it with the eye cream without the composition, after 8 weeks of use, the skin brightness increased by 4.3%, indicating that the composition has the effect of promoting absorption.

[0246] Skin elasticity R2 value, R5 value (as Figure 23 shown), it can be seen from Figure 23 that the test results of skin elasticity are as shown in the figure. When comparing the HPR anti-wrinkle eye cream containing the composition with the HPR eye cream without the composition, from 0 week to 8 weeks, the skin elasticity R2 and R5 values showed a gradually increasing trend. Compared with the skin elasticity R2 value (58.37 ± 0.02316) at 0 week, the skin elasticity R2 value at 8 weeks was 62.71 + 0.03526, an increase of 7.4%. The R5 value increased from 56.25 ± 0.03146 to 64.22 ± 0.04206, an increase of 14.1%. Skin elasticity is closely related to skin aging. When the elastic fibers and collagen fibers of the skin change and gradually lose skin elasticity and tension, it can lead to skin relaxation and wrinkle formation. Using the HPR anti-wrinkle eye cream containing the composition can significantly promote the absorption of HPR and enhance the anti-aging effect. Therefore, it is considered that using the anti-wrinkle eye cream containing the composition has the efficacy of enhancing the absorption of HPR and increasing eye elasticity.

[0247] In summary, the composition has a high ceramide content. By comparing the anti-wrinkle eye cream with the composition and the anti-wrinkle eye cream without the composition, the Sew wrinkle value decreases, the skin brightness increases, and the skin elasticity values R2 and R5 both increase. Therefore, in addition to having moisturizing and repairing properties, the composition can also promote the absorption of active substances and enhance the whitening and anti-aging effects.

[0248] The specific embodiments described herein are merely illustrative of the spirit of the present invention. Those skilled in the art to which the present invention pertains can make various modifications or supplements to the described specific embodiments or use similar methods for substitution, but will not deviate from the spirit of the present invention or exceed the scope defined by the appended claims.

Claims

1. A ceramide cytophospholipid composition prepared by complex coacervation method, characterized in that, It is mainly made of raw materials with the following weight parts: 1 - 5 parts of ceramide, 1 - 5 parts of cell phospholipids, 1 - 5 parts of sodium alginate, 1 - 5 parts of oil, 5 - 15 parts of emulsifier, 1 - 2 parts of acid solution, 0.3 - 1 part of transglutaminase, and 80 - 90 parts of water; The cell phospholipids are positively charged and the sodium alginate is negatively charged, and the cell phospholipids and sodium alginate undergo charge neutralization to cause a coacervation reaction; The hydrophilic group of the cell phospholipids contains a branched-chain structure, and its chemical formula is as follows: In the chemical formula, R1, R2 and R3 are each independently selected from: H, C1 - C4 alkyl groups, and C3 - C4 cycloalkyl groups, and the hydrophobic group of the cell phospholipids contains: a C5 - 30 fatty chain structure.

2. A preparation method of the ceramide cell phospholipid composition according to claim 1 by complex coacervation method, characterized in that, It includes the following preparation steps: Step 1, weigh a certain amount of cell phospholipids and sodium alginate respectively, and stir them in water at 35 - 60 °C to fully dissolve them to obtain a wall material solution; the weight of cell phospholipids and sodium alginate in the wall material solution accounts for 5% of the total weight, that is, the weight ratio of cell phospholipids and sodium alginate to the weight of cell phospholipids, sodium alginate and water is 1:20, and the weight ratio of cell phospholipids to sodium alginate is 1 - 5:1; Step 2, weigh a certain amount of ceramide, stir and dissolve it in a certain amount of oil, and add a certain amount of emulsifier while stirring to obtain an oil phase; Step 3, add the oil phase prepared in Step 2 to the wall material solution prepared in Step 1, and disperse it at high speed to obtain a uniform O / W type emulsion; Step 4, keep the O / W type emulsion prepared in Step 3 at 45 °C for constant-temperature stirring, the speed of constant-temperature stirring is 20 - 550 r / min, adjust the pH to 3.8 - 6.8 with 10% acid solution, and react for 10 - 30 minutes to obtain an emulsion; Step 5, cool the emulsion to 10 - 15 °C, the cooling time is 0.5 - 1 h, adjust the pH to 6.0, add transglutaminase, and solidify it at room temperature for 3.5 - 6.5 h to obtain a solidified composition.

3. The preparation method of a ceramide cell phospholipid composition according to claim 2 by complex coacervation method, characterized in that, The O / W type emulsion is an inclusion solution formed by the oil phase being wrapped inside the wall material.

4. The preparation method of a ceramide cell phospholipid composition according to claim 3 by complex coacervation method, characterized in that, The oil in Step 2 is one or more of soybean oil, octyldodecanol, isononyl isononanoate, camellia oil, olive oil, sweet almond oil, avocado oil, or wheat germ oil, and the weight ratio of ceramide to oil is 1:

2.

5. The preparation method of a ceramide cell phospholipid composition according to claim 4 by complex coacervation method, characterized in that, The emulsifier in Step 2 is one or more of Tween 80, polyglycerol esters, sucrose fatty acid esters, alkyl glycosides, hydrogenated lecithin, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene ethers, fatty acid polyoxyethylene esters, or polyethers.

6. The preparation method of a ceramide cell phospholipid composition according to claim 5 by complex coacervation method, characterized in that, The enzyme activity of the transglutaminase in Step 5 is 100 U / g, the added weight of the transglutaminase is 1 / 3 - 1 / 12 of the total amount of the wall material solution, and the acid solution in Step 4 is hydrochloric acid solution, acetic acid solution, or sulfuric acid solution.

7. The preparation method of a ceramide cell phospholipid composition according to claim 6 by complex coacervation method, characterized in that, The stirring in water at 35 - 60 °C in Step 1, the constant-temperature stirring in Step 4, and the cooling in Step 5 are all under water bath conditions.

8. Non-therapeutic use of a ceramide cytophospholipid composition prepared by complex coacervation method as claimed in claim 1, characterized in that, The ceramide cell phospholipid composition is applied to the human skin alone or mixed with other cosmetics in a certain proportion.

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