A microbead production process with adjustable internal phase based on microfluidic technology and its application

Abstract

The present invention belongs to the field of microbead preparation technology, and specifically relates to a microbead production process with adjustable internal phase based on microfluidic technology and its application. The microbead production process includes the following steps: (1) raw material transportation: the required materials are transported to the microfluidic chip separately through a pump under heat preservation conditions; (2) logistics shearing: the required materials are sheared in the microfluidic chip to obtain composite droplets; (3) cooling and molding: after the sheared droplets are cooled, they are cooled and solidified using a cooling medium to form microbead particles; (4) product collection: the microbead particles and the cooling medium are subjected to solid-liquid separation, filtered, and collected to obtain microbeads. The microbead production process of the present invention can quickly realize the continuous production of double-layer microbeads, realize the precise regulation of the inner layer of the double-layer microbeads, and quickly and accurately control the particle size of the microbeads; at the same time, it can quickly realize the production conversion between single-layer microbeads and double-layer microbeads.

Description

Technical Field

[0001] The present invention belongs to the technical field of microbead preparation, and in particular relates to a microbead production process with adjustable internal phase based on microfluidic technology and its application. Background Art

[0002] Microbeads are widely used in the cosmetics, food, and apparel industries. Depending on the intended use case, their particle size ranges from tens of microns to several millimeters. As a packaging carrier, microbeads hold broad application prospects. While significantly enhancing a product's visual appeal, they can also provide other functionalities. For example, they can be used to encapsulate active ingredients in cosmetics to provide unique benefits; in food, they can be used to impart a distinctive taste; and in clothing, they can be used to encapsulate fragrances for a long-lasting aroma.

[0003] At present, the mainstream preparation processes for microbead products on the market are emulsion method and extrusion method. The emulsion method is to prepare water-in-oil or oil-in-water emulsion, and then polymerize to obtain particles. This method is difficult to achieve precise control of particle size, and the product batch-to-batch difference is large. The extrusion method is to squeeze the raw materials through a porous sieve plate to form droplets, and then the droplets solidify to obtain particles. This method requires the replacement of the sieve plate to prepare different particles, which has high hardware costs. At the same time, the sieve plate must be surface treated to prevent the solution from wetting the sieve plate and preventing droplets from forming. Neither of the above two methods can achieve the preparation of double-layer microbeads.

[0004] Microfluidic chip technology is a technology for precisely manipulating and processing fluids on a microscale, and is widely used in the fields of biomedicine, chemical analysis, etc. One of the applications is to use microfluidic chips to shear and prepare microbeads, which mainly utilizes the flow characteristics of fluids in microchannels to generate droplets or microbeads of uniform size. Currently, most microfluidic chip shearing requires surface modification, because the chip currently used is a two-dimensional structure with flat channels. Droplet shearing cannot be achieved without interface modification, and once modified, it can only be fixed as one type of emulsion, such as oil-in-water or only oil-in-water. For example, the Chinese patent with publication number CN 105213893 A discloses a method for preparing microdroplets based on microfluidic chip modification technology, which uses a sol-gel method to modify the microfluidic chip. It has the characteristics of obvious modification effect and simple operation, and is suitable for preparing microdroplets with complex structures or functions such as oil-in-water type, one-package-multiple type, and magnetic response type.

[0005] Currently, the raw materials of microbeads on the market, especially those used in cosmetics, are all polysaccharides such as cellulose. They have a poor skin feel and can cause a "muddy" effect after application. Therefore, the development of a new microbead production process is of great significance to the further development of the microbead industry. Summary of the Invention

[0006] The purpose of the present invention is to provide a microbead production process with adjustable internal phase based on microfluidic technology and its application.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] A microbead production process with adjustable internal phase based on microfluidic technology, comprising the following steps:

[0009] (1) Raw material transportation: The required materials are transported to the microfluidic chip through different pipelines under heat preservation conditions;

[0010] (2) Logistics shearing: The required materials are sheared in the microfluidic chip to obtain composite droplets;

[0011] (3) Cooling molding: After cooling the composite droplets, use a cooling medium to cool and solidify them to form microbead particles;

[0012] (4) Product collection: Separate the microbead particles and the cooling medium to obtain microbeads.

[0013] Preferably, the microfluidic chip is a three-dimensional structure and is printed using 3D printing technology.

[0014] Preferably, the microfluidic chip includes an inlet tube, a shearing portion and an outlet tube, and the shearing portion is connected to the inlet tube and the outlet tube respectively; the inlet tube includes an external phase inlet tube, an intermediate phase inlet tube and an internal phase inlet tube.

[0015] Preferably, the shearing section includes an external phase pipe, an intermediate phase pipe and an internal phase pipe; the external phase pipe, the intermediate phase pipe and the internal phase pipe are nested and connected in sequence from outside to inside, the external phase in the external phase inlet pipe flows through the external phase pipe, the intermediate phase in the intermediate phase inlet pipe flows through the intermediate phase pipe, and the internal phase in the internal phase inlet pipe flows through the internal phase pipe.

[0016] Preferably, the interior of the outer phase pipe, the interior and exterior of the intermediate phase pipe, and the interior and exterior of the inner phase pipe are all truncated cone structures, the outlets of the outer phase pipe, the intermediate phase pipe, and the inner phase pipe are on the same horizontal plane, and the outer phase pipe, the intermediate phase pipe, and the inner phase pipe all have the same central axis.

[0017] The structure of the microfluidic chip is 3D printed, and the interlacing of the pipes is a spatially staggered arrangement. 3D printing is an integrated molding process. After the chip is 3D modeled, it will be sliced, and then these slices will be stacked layer by layer and printed out to ensure the reasonable connection between the frustum structure of the microfluidic chip and the inlet and outlet pipes.

[0018] It should be noted that the interior of the outer phase pipe refers to the space formed by the inner pipe wall of the outer phase pipe, which is in the shape of a truncated cone. The intermediate phase pipe and the inner phase pipe are both structures with a certain thickness, and the shapes of their inner and outer pipe walls are truncated cones.

[0019] A truncated cone is defined as a geometric solid formed by rotating the sides of a right trapezoid perpendicular to its base, with the line along the waist being the axis of rotation. The term "truncated cone" is a mathematical term.

[0020] Preferably, the density ratio of the intermediate phase to the inner phase is 中间相 :ρ 内相 It is 0.93-1.1.

[0021] Preferably, the angle θ between the outer edge of the outer phase pipe and the plane where the outer phase pipe outlet is located is 60-85°. Too small an angle is not conducive to 3D printing processing, and the larger the angle, the weaker the wrapping shearing effect of the outer phase on the inner phase.

[0022] Preferably, the microfluidic chip is made of metal.

[0023] More preferably, the microfluidic chip is made of 316L stainless steel.

[0024] Preferably, when preparing O / W / O type microbeads, the external phase pipe flows through the oil phase O1, the intermediate phase pipe flows through the water phase W, and the internal phase pipe flows through the oil phase O2; when preparing W / O / W type microbeads, the external phase pipe flows through the water phase W1, the intermediate phase pipe flows through the oil phase O; and the internal phase pipe flows through the water phase W2.

[0025] In the present invention, the liquid flowing through the inner phase pipe is sheared into droplets by the liquid flowing through the middle phase pipe, and then continues to flow along the middle phase pipe, and is finally sheared into double-layer composite droplets by the fluid in the outer phase pipe. The present invention can regulate the shear frequency of the inner phase by controlling the flow rate of the liquid in the middle phase pipe, thereby realizing the transformation of the double-layer droplets from "one package one" to "one package many". When the flow rate of the liquid in the inner phase pipe is fixed, the shear frequency of the inner phase increases as the flow rate of the middle phase increases. The size of the double-layer droplets can be precisely controlled by regulating the flow rates of the middle phase and the inner phase, wherein the influence of the middle phase is greater. To prepare single-layer microbeads, it is only necessary to open one of the middle phase pipe or the inner phase pipe separately, and after the shearing of the liquid in the outer phase pipe, a single-layer pure microbead without an internal structure can be obtained.

[0026] Preferably, the chip used is prepared using metal 3D printing technology to achieve the design and finishing of 3D chips. Compared with traditional microfluidic 2D chips, this chip does not require surface treatment to achieve droplet shearing. Traditional two-dimensional chips require hydrophilic and hydrophobic treatment of the chip surface to ensure droplet shearing. At the same time, unlike devices assembled with glass tubes or iron tubes, it is difficult to ensure the alignment of the center lines of the pipelines, which affects the droplet shearing. The microfluidic chip of the present invention is prepared using a metal 3D printer, which can fully ensure the alignment of the center lines of the inlet pipe and the outlet pipe. The alignment of the center lines allows the inner phase to be completely wrapped by the intermediate phase, and then the intermediate phase is wrapped and sheared by the outer phase. At the same time, 3D printing is used to achieve a gradual frustum transition of the outlet section of the inner phase and intermediate phase pipelines. The frustum transition can greatly enhance the shearing ability of the logistics and achieve efficient generation of double-layer droplets.

[0027] The chip used in this invention has a three-dimensional structure. The outlet structure of each phase pipe can be perfectly nested with the previous one. The outlet of the inner phase pipe can be perfectly nested with the intermediate phase pipe; the outlet of the intermediate phase pipe can be perfectly nested with the outer phase pipe, without the need for pipe surface treatment. The outlets of the intermediate and inner phase pipes are truncated cone structures. This structure facilitates the complete encapsulation of the fluid in the pipe by the external fluid and can also generate a good shear force, so that the fluid in the pipe is sheared evenly and efficiently.

[0028] The microfluidic chip of the present invention, based on 3D printing technology, enables the precise fabrication of a fully nested structure, ensuring the concentricity of all pipelines, thereby ensuring uniform and repeatable droplet preparation. Furthermore, the fully nested structure and staggered arrangement of the fluid flow field ensure uniform distribution, ensuring that the inner phase is uniformly wrapped and sheared by the middle phase, and the middle phase is uniformly wrapped and sheared by the outer phase, resulting in the desired droplet product.

[0029] Preferably, when preparing W / O / W type microbeads, the external phase is: aqueous phase W1, an aqueous solution of one or more combinations of emulsifiers, high-molecular polymers, thickeners, and pigments; the intermediate phase is: oil phase O, an oil of one or more combinations of solid oils, liquid oils, thickeners, emulsifiers, oil-soluble active substances, and pigments; the internal phase is: aqueous phase W2, an aqueous solution of one or more combinations of thickeners, emulsifiers, water-soluble active substances, various water-soluble carriers, and pigments.

[0030] Preferably, when preparing O / W / O type microbeads, the external phase is: oil phase O1, solid oil, liquid oil, thickener, emulsifier, pigment or one combination of oil; the middle phase is: water phase W, thickener, emulsifier, water-soluble active substance, various water-soluble carriers, pigment or one combination of aqueous solution; the internal phase is: oil phase O2, solid oil, liquid oil, thickener, emulsifier, oil-soluble active substance, pigment or one combination of oil.

[0031] Preferably, the densities of the middle and inner phases are adjusted so that the densities of the two phases are close, with a density ratio of ρmiddlephase:ρinnerphase = 0.93-1.1, preferably 0.96. This ensures that the inner droplets of the composite droplets remain relatively centered after shearing, thereby reducing the risk of inner phase leakage. Density adjustment is achieved by varying the proportions of the individual components of each phase.

[0032] The present invention adopts metal 3D printing technology, uses 316L stainless steel as raw material, has a printing accuracy of 60μm, and the metal chip is resistant to high temperature and high pressure.

[0033] The micro-bead materials used in the present invention are natural oils, various natural plant extracts, animal oils and fats, glycerides and other esters, and alkanes such as paraffin and microcrystalline wax.

[0034] The present invention provides an application of a microbead production process with adjustable internal phase based on microfluidic technology in preparing microbeads.

[0035] The present invention provides the application of the microbead production process with adjustable internal phase based on microfluidic technology in the preparation of microbeads used in the fields of cosmetics, food and clothing.

[0036] Compared with the prior art, the advantages and beneficial effects of the present invention are:

[0037] 1. Conventional microfluidic chip shearing requires surface modification because the chip is a two-dimensional structure with flat channels. Droplet shearing cannot be achieved without interface modification, and once modified, it can only be fixed as one type of emulsion, such as oil-in-water or oil-in-water. The chip of the present invention is a three-dimensional structure. Such channels can be nested, and the misalignment can achieve active wrapping of logistics, eliminating the influence of the pipe wall on the sheared phase, thus eliminating the need for surface modification. Therefore, the application range of this chip is wider. This technology has a wider range of applications and is more applicable to formulations;

[0038] 2. The present invention can rapidly realize continuous production of double-layer microbeads; can achieve precise control of the inner layer of the double-layer microbeads (the content of the inner layer is controlled by the flow rate ratio of the inner phase to the middle phase, and the number of droplets in the inner layer and the particle size are controlled by the flow rates of the middle phase and the outer phase); can achieve rapid and precise control of the particle size of the microbeads; can quickly realize the production conversion between pure microbeads and double-layer microbeads; based on the double-layer structure, it can realize the combined design of the outer and inner layer functions, enriching the functions of the microbead products;

[0039] 3. Based on microfluidic technology, this invention realizes the rapid and controllable production of double-layer microbeads. The double-layer structure of the microbeads can realize the combined design of the outer and inner layer functions, enriching the functions of the microbead products and launching a new functional microbead product;

[0040] 4. The 3D chip of the present invention can be directly replaced in the equipment using the chip modified by the prior art. Only the chip needs to be replaced, and the rest of the material pumping system is consistent with the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is a schematic diagram of the microbead production process;

[0042] Figure 2 This is a shear schematic diagram of the microbead production process;

[0043] Figure 3 Schematic diagram of the cross section of the microfluidic chip;

[0044] Figure 4 Schematic diagram of the microfluidic chip;

[0045] Figure 5 This is a microscope image of the microbeads prepared in Example 1;

[0046] Figure 6 This is a microscope image of the microbeads prepared in Example 3;

[0047] Figure 7 This is a microscope image of the microbeads prepared in Example 4;

[0048] Figure 8 This is a microscope image of the microbeads prepared in Example 5;

[0049] Figure 9 This is a microscope image of the microbeads prepared in Example 7;

[0050] Figure 10 This is a microscope picture of the microbeads prepared in Example 8;

[0051] Figure 11 This is a microscope picture of the microbeads prepared in Example 10;

[0052] Figure 12 This is a microscope picture of the microbeads prepared in Example 13;

[0053] Figure 13 This is a microscope picture of the microbeads prepared in Example 15;

[0054] Figure 14 This is a microscope picture of the microbeads prepared in Example 16.

[0055] In the figure, A is a decomposed schematic diagram of the microfluidic chip, and B is a nested schematic diagram of the microfluidic chip, 1. inlet pipe, 11. external phase inlet pipe, 12. intermediate phase inlet pipe, 13. internal phase inlet pipe, 2. shear part, 21. external phase pipe, 22. intermediate phase pipe, 23. internal phase pipe, 3. outlet pipe, 4. frustum nested structure. DETAILED DESCRIPTION

[0056] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0057] See also Figure 2-3 , according to the structure of the microfluidic chip shown in 2-3, the interlaced pipes are arranged in a spatial dislocation, and 3D printing is an integrated molding. After the chip is 3D modeled, it will be sliced, and then these slices will be stacked layer by layer and printed. It should be noted that Figure 3 What is mainly shown in the figure is a schematic diagram of the frustum structure. The other pipeline structures of the microfluidic chip are printed based on the specific pipeline design. This is a routine operation of 3D printing technology and will not be described here.

[0058] The microfluidic chip is a three-dimensional structure, printed using 3D printing technology, and is made of 316L stainless steel. The chip includes an inlet tube 1, a shearing section 2, and an outlet tube 3. The shearing section 2 is connected to the inlet tube 1 and outlet tube 3, respectively. The inlet tube 1 includes an external phase inlet tube 11, an intermediate phase inlet tube 12, and an internal phase inlet tube 13. The shearing section 2 includes an external phase conduit 21, an intermediate phase conduit 22, and an internal phase conduit 23. These conduits 21, 22, and 23 are nested from outside to inside, forming a truncated cone nested structure 4. Liquid from the external phase inlet tube 11 flows through the external phase conduit 21, liquid from the intermediate phase inlet tube 12 flows through the intermediate phase conduit 22, and liquid from the internal phase inlet tube 13 flows through the internal phase conduit 23. The interior of the external phase conduit 21, the interior and exterior of the intermediate phase conduit 22, and the interior and exterior of the internal phase conduit 23 are all truncated cones, with a height of 10 mm. The outlets of the outer phase pipe 21, the middle phase pipe 22 and the inner phase pipe 23 are on the same horizontal plane, and the outer phase pipe 21, the middle phase pipe 22 and the inner phase pipe 23 all share the same central axis. The angle θ between the outer edge of the outer phase pipe 21 and the plane where the outlet of the outer phase pipe 21 is located is 70°.

[0059] See also Figure 1 A microfluidic microbead production process with adjustable internal phase comprises the following steps:

[0060] (1) Raw material transportation: The required materials are transported to the microfluidic chip through different pipelines under heat preservation conditions;

[0061] (2) Logistics shearing: The required materials are sheared in the microfluidic chip to obtain composite droplets;

[0062] (3) Cooling molding: After cooling the composite droplets, use a cooling medium to cool and solidify them to form microbead particles;

[0063] (4) Product collection: Separate the microbead particles and the cooling medium to obtain microbeads.

[0064] The following examples produced different types of microbeads using the above-described production process. When preparing a single layer of microbeads, only the mesophase and exophase channels were opened. The equipment used was a microbead / microcapsule synthesizer (a commercially available product from Moge Microfluidics Technology Co., Ltd.), onto which the microfluidic chip was directly mounted.

[0065] Example 1 Preparation of O / W microbeads, single layer, GTCC liquid grease thickening

[0066] Raw material preparation:

[0067] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0068] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0069] Logistics shearing: Flow rate setting: external phase: 50 mL / min; intermediate phase: 6 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0070] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a single layer of pure microbead products.

[0071] Example 2 Preparation of O / W microbeads, single layer, AB liquid grease thickening

[0072] Raw material preparation:

[0073] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0074] Intermediate phase: Prepare a dispersion of 5% by mass of polyamide-8 and 1% by mass of Span 80 containing C12-15 alkyl benzoate, stir well and keep warm at 70°C for later use;

[0075] Logistics shearing: Flow rate setting: external phase: 50 mL / min; intermediate phase: 6 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0076] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a single layer of pure microbead products.

[0077] Example 3 Preparation of W / O / W microbeads, double layer, one-in-one, common inner water phase, GTCC liquid oil thickening

[0078] Raw material preparation:

[0079] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0080] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0081] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0082] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0083] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0084] Example 4 Preparation of W / O / W microbeads, double layer, two in one package, common inner water phase, GTCC liquid oil thickening

[0085] Raw material preparation: External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0086] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0087] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0088] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 0.8 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0089] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0090] Example 5 Preparation of W / O / W microbeads, double layer, multiple in one package, common inner water phase, GTCC liquid oil thickening

[0091] Raw material preparation:

[0092] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0093] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0094] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0095] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 0.5 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0096] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0097] Example 6, Preparation of W / O Microbeads, Monolayer, Agar Aqueous Solution

[0098] Raw material preparation:

[0099] External phase: Prepare a white oil dispersion of 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70℃ for later use.

[0100] Intermediate phase: prepare an aqueous solution of 5% PVA, 3% agar, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use;

[0101] Logistics shearing: The flow rate is set to 50 mL / min for the external phase and 6 mL / min for the intermediate phase. After setting the flow rate, start the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0102] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a single layer of pure microbead products.

[0103] Example 7, Preparation of O / W / O Microbeads, Double Layer, One-in-One, Agar-Aqueous Solution

[0104] Raw material preparation:

[0105] External phase: Prepare a white oil dispersion of 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70℃ for later use

[0106] Intermediate phase: prepare an aqueous solution of 5% PVA, 3% agar, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use;

[0107] Internal phase: prepare a GTCC dispersion with 5% mass fraction of rose essential oil and 1% mass fraction of Span 80, stir well and keep warm at 70℃ for later use;

[0108] Logistics shearing: Flow rate setting: external phase: 50 mL / min; middle phase: 6 mL / min, inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0109] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a single layer of pure microbead products.

[0110] Example 8: Preparation of W / O / W microbeads, wax beads, common internal water phase, jojoba esters (solid oil)

[0111] Raw material preparation:

[0112] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0113] Mesophase: Prepare a jojoba ester dispersion containing 5% by mass of castor oil / IPDI copolymer, 1% by mass of Span 80, and a small amount of pigment. Stir well and keep warm at 70°C.

[0114] Internal phase: prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use.

[0115] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0116] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0117] Example 9 Preparation of W / O / W microbeads, double layer, one-in-one, inner water phase plus liposomes, GTCC liquid oil

[0118] Raw material preparation:

[0119] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0120] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0121] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80, 1% ceramide liposome and a small amount of pigment, stir well and keep warm at 70℃ for later use.

[0122] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0123] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0124] Example 10: Preparation of W / O / W type microbeads, double layer, one-in-one, with liposomes added to the inner aqueous phase, color speed added to the oil phase, and GTCC liquid oil thickening.

[0125] Raw material preparation:

[0126] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0127] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer, 1% by mass of Span 80, and a small amount of pigment. Stir well and keep warm at 70°C.

[0128] Internal phase: prepare an aqueous solution of 8% PVA by mass, 1% Tween 80 by mass, 1% ceramide liposome by mass and a small amount of pigment, stir well and keep warm at 70°C for later use.

[0129] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0130] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0131] Example 11 Preparation of W / O / W type microbeads, double layer, one-in-one, common inner water phase, oil phase with VE, GTCC liquid oil thickening.

[0132] Raw material preparation:

[0133] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0134] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0135] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0136] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0137] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0138] Example 12: Preparation of W / O / W type microbeads, double layer, one package one, adding three active ingredients to the inner water phase, and GTCC liquid oil thickening.

[0139] Raw material preparation:

[0140] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0141] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0142] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80, 0.1% bosine, 0.1% ergothioneine, 0.1% ectoine and a small amount of pigment, stir well and keep warm at 70℃ for later use.

[0143] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0144] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0145] Example 13: Preparation of W / O / W type microbeads, double layer, one-in-one, with color powder added to the inner water phase and GTCC liquid oil thickening.

[0146] Raw material preparation:

[0147] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0148] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0149] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80, 0.5% mica powder and pigment, stir well and keep warm at 70℃ for later use.

[0150] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0151] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0152] Example 14: Preparation of W / O / W microbeads, double-layer, one-in-one, common inner water phase, oil phase thickened with lithospermum oil (mixed oil)

[0153] Raw material preparation:

[0154] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0155] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer, 1% by mass of Span 80, and 50% by mass of lithospermum officinale oil, stir well, and keep warm at 70°C for later use;

[0156] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0157] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 2 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0158] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0159] Example 15, Preparation of W / O / W microbeads, double layer, one package one, common inner water phase, GTCC liquid oil thickening, flow rate adjustment, particle size control

[0160] Raw material preparation:

[0161] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0162] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0163] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0164] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 8 mL / min; inner phase: 2.7 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0165] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0166] Example 16, Preparation of W / O / W type microbeads, double layer, one package one, common inner water phase, GTCC liquid oil thickening, adjusting flow rate, inner water phase ratio

[0167] Raw material preparation:

[0168] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0169] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0170] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0171] Logistics shearing: The flow rate is set as external phase: 50 mL / min; middle phase: 6 mL / min; inner phase: 4 mL / min. After setting the flow rate, turn on the feed pump to transport each phase to the shearing section for logistics shearing to obtain droplets.

[0172] Comparative Example 1: Preparation of microbeads using a chip without a cone tip design

[0173] Raw material preparation:

[0174] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0175] Mesophase: Prepare a GTCC dispersion containing 5% by mass of castor oil / IPDI copolymer and 1% by mass of Span 80, stir well and keep warm at 70°C.

[0176] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0177] Logistics shearing: Set the flow rate to 50 mL / min for the external phase, 6 mL / min for the middle phase, and 2 mL / min for the internal phase. After setting the flow rate, start the feed pump to transport each phase to the shearing section for logistics shearing.

[0178] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads. You cannot obtain a "one-in-one" double-layer microbead product. Only simple oil beads can be collected, and the inner phase cannot be encapsulated.

[0179] Comparative Example 2: Castor oil / IPDI copolymer without thickener added to the oil phase

[0180] Raw material preparation:

[0181] External phase: Prepare an aqueous solution of 8% PVA and 1% Tween 80, stir well and keep warm at 70℃ for later use;

[0182] Intermediate phase: prepare GTCC dispersion with 1% Span 80 by mass, stir and keep warm at 70℃ for later use;

[0183] Internal phase: prepare an aqueous solution of 8% PVA, 1% Tween 80 and pigment, stir well and keep warm at 70℃ for later use.

[0184] Logistics shearing: Set the flow rate to 50 mL / min for the external phase, 6 mL / min for the middle phase, and 2 mL / min for the internal phase. After setting the flow rate, start the feed pump to transport each phase to the shearing section for logistics shearing.

[0185] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, the solidified microbeads are picked up, but no microbead products are obtained. Liquid oil droplets come out of the outlet pipe, which will quickly coalesce and no microbeads can be obtained.

[0186] Cooling and collection: Add the droplets to cold water at 4°C. After cooling, pick up the solidified microbeads to obtain a "one-in-one" double-layer microbead product.

[0187] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A microbead production process with adjustable internal phase based on microfluidic technology, characterized in that: The following steps are involved: (1) Raw material transportation: The required materials are transported to the microfluidic chip through different pipelines under heat preservation conditions; (2) Logistics shearing: The required materials are sheared in the microfluidic chip to obtain composite droplets; the microfluidic chip is a three-dimensional structure and is printed by 3D printing technology; the microfluidic chip includes an inlet pipe, a shearing part and an outlet pipe, and the shearing part is connected to the inlet pipe and the outlet pipe respectively; the inlet pipe includes an external phase inlet pipe, an intermediate phase inlet pipe and an internal phase inlet pipe; (3) Cooling molding: After cooling the composite droplets, use a cooling medium to cool and solidify them to form microbead particles; (4) Product collection: The microbead particles and the cooling medium are separated to obtain microbeads; the shearing section includes an external phase pipe, an intermediate phase pipe and an internal phase pipe; the external phase pipe, the intermediate phase pipe and the internal phase pipe are nested and connected in sequence from the outside to the inside, the external phase in the external phase inlet pipe flows through the external phase pipe, the intermediate phase in the intermediate phase inlet pipe flows through the intermediate phase pipe, and the internal phase in the internal phase inlet pipe flows through the internal phase pipe; the interior of the external phase pipe, the interior and exterior of the intermediate phase pipe, and the interior and exterior of the internal phase pipe are all truncated cone structures, the outlets of the external phase pipe, the intermediate phase pipe and the internal phase pipe are on the same horizontal plane, and the external phase pipe, the intermediate phase pipe and the internal phase pipe all have the same central axis; when preparing O / W / O type microbeads, the external phase pipe flows through the oil phase O1, the intermediate phase pipe flows through the water phase W, and the internal phase pipe flows through the oil phase O2; when preparing W / O / W type microbeads, the external phase pipe flows through the water phase W1, the intermediate phase pipe flows through the oil phase O; and the internal phase pipe flows through the water phase W2.

2. The microbead production process with adjustable internal phase based on microfluidic technology according to claim 1, characterized in that: The density ratio of the middle phase to the inner phase ρ 中间相 :ρ 内相 It is 0.93-1.

1.

3. The microbead production process with adjustable internal phase based on microfluidic technology according to claim 1, characterized in that: The angle θ between the outer edge of the external phase pipe and the plane where the external phase pipe outlet is located is 60-85°.

4. The microbead production process with adjustable internal phase based on microfluidic technology according to claim 1, characterized in that: The material of the microfluidic chip is metal.

5. Use of the microbead production process with adjustable internal phase based on microfluidic technology according to any one of claims 1 to 4 in the preparation of microbeads for use in the fields of cosmetics, food and clothing.

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