Calcium alginate microbeads, and preparation method and application thereof

Abstract

This invention belongs to the field of microbead technology, specifically relating to calcium alginate microbeads, their preparation method, and applications. The preparation method includes the following steps: (1) preparing an external phase, an internal phase, and a receiving liquid; the external phase includes sodium alginate; (2) simultaneously introducing the internal phase and the external phase into a microfluidic chip to obtain microdroplets; (3) the microdroplets fall into the receiving liquid, solidify, are retrieved, washed, and then the calcium alginate microbeads are obtained. This invention can achieve efficient and continuous production of double-layer encapsulated microbeads; achieve precise control of the internal phase of double-layer microbeads and precise control of the microbead particle size; simultaneously achieve controllable conversion between pure microbeads and double-layer encapsulated microbeads; the microbeads have uniform particle size; and the product batch consistency is high.

Description

Technical Field

[0001] This invention belongs to the field of microbead technology, specifically relating to a calcium alginate microbead, its preparation method, and its application. Background Technology

[0002] Microbeads are a widely used functional material that is now widely applied in cosmetics, food, textiles and clothing and other fields. While effectively improving the appearance and texture of products and enhancing their visual presentation, microbeads can also endow products with a variety of additional functions. As a high-performance core coating carrier, microbeads have broad market application and development prospects.

[0003] Gel microbeads are one of the most widely used types of microbeads. They are mainly used in the food industry to prepare various jellies or popping beads, and colored particles in cosmetics. Currently, the main preparation method of gel microbeads is the droplet method: droplets are squeezed out using a needle. When the droplets accumulate to a certain size, they fall from the needle due to gravity. The droplets fall into the receiving liquid below and solidify and crosslink to form microbeads. The droplet method has the following disadvantages: (1) Since the droplet method relies on the natural dripping of droplets, the production capacity of a single needle is very low. A large number of needles are needed for parallel production, often several hundred needles in parallel. It is difficult to distribute the material evenly, and the particle uniformity of the product is poor; (2) It is difficult to control the particle size of droplets, mainly because it is based on the gravity dripping of droplets; (3) The droplet method is mainly used to produce single-layer microbeads without coating, and it is difficult to realize the production of double-layer coated microbeads.

[0004] Chinese patent CN118558301A discloses a porous sodium alginate / cellulose nanofiber gel microsphere and its preparation method and application. The method involves mixing an aqueous solution of sodium alginate / cellulose nanofiber / polyethylene glycol with an oil phase using a standard glass microfluidic chip to obtain a water-in-oil emulsion. This emulsion is then piped into a stirred CaCl2 solution via a conduit and reacted for 6-12 hours to form microspheres. The microspheres are then washed with isopropanol for 4-12 hours to remove the oil phase, followed by washing with deionized water for 24-48 hours to remove the polyethylene glycol. Finally, the microspheres are freeze-dried to obtain dry porous sodium alginate / cellulose nanofiber gel microspheres. However, this method requires washing with isopropanol for 4-12 hours to remove the oil phase and with deionized water for 24-48 hours, totaling 28-60 hours for the washing process alone. This excessively long and cumbersome process directly leads to low production efficiency and high costs. In addition, the reaction and solidification of microspheres in calcium chloride solution takes 6-12 hours, and the entire preparation process, from reaction and cleaning to drying, may take more than 3-4 days, which is extremely inefficient.

[0005] Therefore, developing a process for efficiently preparing high-quality microbeads is of great significance for promoting the widespread application of microbeads. Summary of the Invention

[0006] To address the aforementioned problems, this invention provides a method for preparing calcium alginate microspheres, which enables efficient and continuous production of double-layer encapsulated calcium alginate microspheres; achieves precise control of the internal phase of the double-layer microspheres and accurate control of the microsphere particle size; simultaneously enables controllable conversion between pure microspheres and double-layer encapsulated microspheres; produces microspheres with uniform particle size; and ensures high batch-to-batch consistency of the product.

[0007] To achieve the above objectives, the present invention provides the following technical solution: The first aspect of the present invention provides a method for preparing calcium alginate microbeads, comprising the following steps: (1) Prepare the external phase, internal phase and receiving liquid separately; the external phase is an aqueous phase, including sodium alginate and water; the internal phase is an oil phase; (2) The inner phase and the outer phase are simultaneously introduced into the microfluidic chip to obtain droplets; the microfluidic chip is located above the receiving liquid, and the microfluidic chip includes an outer phase channel and an inner phase channel, with the inner phase channel disposed inside the outer phase channel; the bottom of the outer phase channel is provided with an outlet hole; (3) The droplets fall into the receiving liquid and solidify. The solidified beads are then picked up and washed with pure water to remove the residual calcium chloride receiving liquid, thus obtaining calcium alginate microbeads.

[0008] This invention designs a microfluidic chip that utilizes a special microchannel structure to achieve the focusing and convergence of the external phase and the internal phase in the focusing region. A jet column of liquid, with the external phase encapsulating the internal phase, is formed at the microfluidic chip outlet. After maintaining a certain length, the liquid column spontaneously decomposes into discrete droplets under the drive of surface tension. These droplets have a bilayer structure where the external phase encapsulates the internal phase. Upon falling into the receiving liquid, the external phase and the receiving liquid undergo a cross-linking reaction, forming O / W type microspheres. Due to the jet flow, the material flow rate is very high, significantly increasing the yield of microsphere products. Four chips connected in parallel can achieve a production capacity of 100 kg in 8 hours.

[0009] The preparation method of the microbeads of this invention is simple to clean, which greatly saves time and cleaning costs. The specific cleaning method is as follows: the solidified beads are picked up, soaked in pure water, stirred slightly, picked up again, soaked in pure water again, and washed repeatedly 3 to 4 times to obtain calcium alginate microbeads.

[0010] Preferably, the inner phase pipe is cylindrical.

[0011] Preferably, the central axis of the inner phase pipe coincides with the central axis of the outlet hole of the outer phase pipe.

[0012] Preferably, the focusing angle between the lower side of the outer phase pipe and the plane where the outlet hole of the outer phase pipe is located is θ; θ is 0-70°.

[0013] Preferably, the lower part of the outer phase pipe is truncated cone-shaped. Note: A truncated cone is a geometric body formed by rotating a right trapezoid around the axis of rotation of its legs perpendicular to the base, with the remaining sides forming a curved surface.

[0014] Preferably, the focusing angle between the lower side of the outer phase pipe and the plane where the outlet hole of the outer phase pipe is located is θ; θ is 15-50°.

[0015] Preferably, the vertical distance between the bottom surface of the inner phase pipe and the plane containing the outlet hole of the outer phase pipe is D, where D is 0.5-5mm, and more preferably D is 1-2mm.

[0016] Preferably, the vertical distance between the plane of the outlet hole of the external phase pipe and the surface of the receiving liquid is H, where H is 50-300mm, and more preferably H is 100-260mm.

[0017] Preferably, the inner phase pipe is cylindrical, and the inner diameter of the inner phase pipe is 0.6-3mm, preferably 1-2mm.

[0018] Preferably, the diameter of the outlet hole is 0.6-2mm, more preferably 0.6-1.5mm.

[0019] Preferably, the flow rate ratio of the external phase to the internal phase is (1-20):1.

[0020] More preferably, the flow rate ratio of the external phase to the internal phase is (2-10):1. The inventors have found that when the flow rate ratio of the external phase to the internal phase is (2-10):1, the particle size of the microspheres is more uniform.

[0021] More preferably, the flow rate ratio of the external phase to the internal phase is (5-10):1.

[0022] Preferably, the internal phase flow rate is in the range of 0.1-100 mL / min, more preferably 10-80 mL / min. Preferably, the ratio of the sum of the internal and external phase flow rates Q to the receiving height H is 1 mL / min: (2~9) mm.

[0023] More preferably, the ratio of the sum of the flow rates of the inner and outer phases Q to the receiving height H is 1 mL / min: (3~8) mm.

[0024] The inventors discovered that when the ratio of the sum of the internal and external phase flow rates to the receiving height is maintained at 1 mL / min: (3~8) mm, calcium alginate gel microbeads with better microstructure uniformity can be prepared; at the same time, the batch stability of the product is better.

[0025] The inventors also discovered that when the flow rate is low during the microsphere production process, the liquid column will decompose into droplets after maintaining a short length. A lower flow rate (H) is needed to receive the droplets. If H is too high, the droplet impact force is too great, making them easily broken and causing leakage of the internal phase. When the production flow rate is high, the liquid column will maintain a longer length, so it is necessary to increase H to receive the droplets. A lower flow rate results in encapsulated fibers.

[0026] Preferably, the external phase further includes one or more combinations of emulsifiers, high-molecular polymers, thickeners, pigments, color powders, and bacterial powders.

[0027] Preferably, the internal phase is an oil phase.

[0028] Preferably, when the internal phase is an oil phase, the viscosity of the internal phase at room temperature is 5~300 cP.

[0029] More preferably, when the internal phase is an oil phase, the viscosity of the internal phase at room temperature is 40~120 cP.

[0030] The room temperature is 22-27℃.

[0031] The inventors discovered that when the internal phase is an oil phase, the viscosity of the internal phase has a significant impact on the uniformity of the microspheres, and when the viscosity is in the range of 40~120 cP, the CV value of the microspheres can be better achieved.

[0032] Preferably, the internal phase includes at least one of solid grease and liquid oil.

[0033] Preferably, the internal phase comprises soybean oil.

[0034] Preferably, the internal phase further includes one or more of the following: thickener, emulsifier, oil-soluble active ingredient, pigment, color powder, and bacterial powder.

[0035] Preferably, the internal phase is an aqueous phase. The internal phase includes sodium alginate and water.

[0036] Preferably, the receiving liquid is an aqueous solution of a soluble calcium salt.

[0037] Preferably, the receiving liquid is at least one of calcium chloride aqueous solution and calcium nitrate aqueous solution, and the mass fraction of calcium salt is 0.1-10%, preferably 1-5%.

[0038] The preparation method of this invention can achieve controllable conversion between pure microspheres and double-layer encapsulated microspheres. Pure microspheres can be prepared without opening the internal phase, while double-layer encapsulated microspheres can be prepared by opening the internal phase. A second aspect of this invention provides calcium alginate microspheres.

[0039] Preferably, the average particle size of the microspheres is 1mm-4mm.

[0040] Preferably, the coefficient of variation of the microbeads is <9%.

[0041] The microspheres of this invention are prepared by achieving a balance between factors such as microfluidic chip structure, external and internal phase flow rates, surface tension, fluid inertia, and internal phase viscosity. Surface tension acts as a driving force, reducing the system energy by decreasing the total surface area, causing the liquid column to disturb and tend to break up. Fluid inertia resists this motion, and surface tension must first overcome the fluid inertia to drive the disturbance growth. Internal phase viscosity further dissipates the disturbance energy, while surface tension provides the driving force for instability. Inertia and viscosity constitute resistance from the perspectives of momentum and dissipation, respectively. Ultimately, a synergistic balance is achieved within a specific wavelength and time. The synergistic effect of multiple conditions results in microspheres with good formability, uniform particle size, and high stability.

[0042] A third aspect of this invention provides an application of calcium alginate microbeads.

[0043] Preferably, the calcium alginate microbeads are used in the preparation of cosmetics, food, or textiles and clothing.

[0044] The microfluidic chip of this invention can also be used to produce calcium alginate fiber.

[0045] The beneficial effects of this invention are as follows: 1. This invention has high production efficiency and can achieve large-scale mass production. When four microfluidic chips work simultaneously, 100 kg-level microsphere products can be stably produced within 8 hours. The production efficiency is dozens of times higher than that of existing technologies, which fully meets the needs of large-scale industrial production. 2. This invention enables continuous production and precise structural control of bilayer microspheres, with a simple and efficient process flow. Furthermore, by independently controlling the internal phase flow rate, the size and morphology of the inner gel core can be precisely controlled; by adjusting the ratio of internal and external phase flow rates and the total flow rate, the overall particle size of the final microspheres can be flexibly controlled, achieving precise customization from tens to hundreds of micrometers, meeting the diverse size requirements of different application scenarios. 3. The product of this invention has rich functions and flexible production mode switching. It can realize independent combination design of outer and inner layer functions, such as loading different active substances, drugs or functional materials onto the inner and outer layers respectively, giving the microbeads composite functions such as synergistic effect and time-sequential release, which significantly enriches the application dimensions of the product. At the same time, the production system can quickly switch between pure microbeads and double-layer microbeads without changing complex equipment, which greatly improves the adaptability and flexibility of the production line. 4. Unlike existing technologies that require prolonged cleaning with organic solvents to remove the oil phase, this application uses a water-based receiving liquid system. After microsphere molding, only a small amount of water-soluble receiving liquid remains on the surface, which can be quickly removed with a simple rinse with deionized water. This significantly shortens the post-processing time and simplifies the process. It also avoids the use and recycling issues of organic solvents, making it safer and more environmentally friendly, and reducing production costs. Attached Figure Description

[0046] Figure 1 This is a schematic diagram illustrating the shearing principle of the preparation method of the present invention; Figure 2 The droplet formation process of the fractured segment of the present invention, as recorded by a high-speed camera; Figure 3 A schematic diagram of the microbeads prepared in Example 1; Figure 4 A schematic diagram of the microbeads prepared in Example 2; Figure 5 A schematic diagram of the microbeads prepared in Example 3; Figure 6 A schematic diagram of the microbeads prepared in Example 4; Figure 7 A schematic diagram of the microbeads prepared in Example 5; Figure 8 A schematic diagram of the microbeads prepared in Example 6; Figure 9 A schematic diagram of the microbeads prepared in Example 7; Figure 10 A schematic diagram of the microbeads prepared in Example 8; Figure 11 A schematic diagram of the microbeads prepared in Example 13; Figure 12 A schematic diagram of the product prepared in Comparative Example 1; Figure 13 A schematic diagram of the product prepared in Comparative Example 2; Figure 14 A schematic diagram of the microbeads prepared in Example 14; Figure 15 A schematic diagram of the microbeads prepared in Example 14; Figure 16 This is a schematic diagram of fibers; Figure 17 This is a magnified schematic diagram of the fiber. Detailed Implementation

[0047] The technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0048] Unless otherwise specified, all components used in this invention can be obtained by those skilled in the art through conventional purchase.

[0049] Examples 1-13, Comparative Examples 1-2, and the fiber preparation used the following microfluidic chip: An inner phase channel is located inside an outer phase channel. The inner phase channel is cylindrical with an inner diameter of 2 mm. The upper part of the outer phase channel is cylindrical with an inner diameter of 4 mm. The vertical distance D between the bottom surface of the inner phase channel and the plane containing the outlet orifice of the outer phase channel is 1 mm. The focusing angle θ between the lower side of the outer phase channel and the plane containing the outlet orifice is 20°. The outlet orifice diameter is 1 mm. The vertical distance H between the plane containing the outlet orifice of the outer phase channel and the surface of the receiving liquid is 150 mm.

[0050] Figures 3-11 The microbead images were taken using an optical microscope and an industrial camera, at a magnification of 8x.

[0051] The testing method for the CV value (Coefficient of Variation) of microbeads is as follows: Microbeads are photographed using a microscope, and each microbead is automatically identified through AI image processing to calculate its equivalent circle diameter. The CV value is then calculated using the CV value calculation formula.

[0052] Where, d i Let be the particle size of the i-th microbead. The average particle size of all microbeads is n, which is the number of microbeads in the sample. In the following examples, n is 300.

[0053] Soybean oil: Commercially available Fulinmen premium grade 1 soybean oil.

[0054] Castor oil / IPDI copolymer: DKSH Chemical International Trading (Shanghai) Co., Ltd., Estogel_M; Lecithin: Aoyuan, Ultralc P; Peppermint essential oil: Ji'an Zhongxiang Natural Plant Co., Ltd., DF-02; Different pigments: Guangzhou Zhenbang Daily Chemical Co., Ltd., UNICERT YELLOW K7064-J; UNICERT GREEN K7016-J; UNICERTVIOLET K7014-J; Guangzhou Xulang Biotechnology Co., Ltd., Yuchuang Blue Oil Hydrocarbon; Shanghai Luya Biotechnology Co., Ltd., Annona Orange, Cochineal Red; Purple fluorescent powder: Guangzhou Zhaoheng Trade Development Co., Ltd., EC-441S; Probiotic powder: Beijing Ketuo Hengtong Biotechnology Co., Ltd.

[0055] Example 1 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil, 0.1% purple pigment. The viscosity of the internal phase at room temperature (25℃) is 52 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 20 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm, and the ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:6.25 (mL / min:mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped out again. This process is repeated three times to obtain the microbead product. The CV value of the microbeads is 8.21%. See [link to product details]. Figure 3 .

[0056] Example 2 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil, 0.2% purple pigment. The viscosity of the internal phase at room temperature (25℃) is 54 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 3 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm, and the ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.55 (mL / min:mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped up again. This process is repeated three times to obtain the microbead product. The CV value of the microbeads is 6.59%. See [link to product details]. Figure 4 .

[0057] Example 3 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil and 0.2% pink pigment. The viscosity of the internal phase at room temperature (25℃) is 54 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set as follows: external phase 40 mL / min; internal phase 2 mL / min. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm, and the ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:3.57 (mL / min: mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped up again. This process is repeated three times to obtain the microbead product. Due to the excessively high flow rate ratio between the external and internal phases, the internal phase is easily sheared to an excessively small size and uneven distribution during production. The CV value of the microbeads is 25.92%. See [link to relevant documentation]. Figure 5 .

[0058] Example 4 This embodiment prepares pure microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase and internal phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate of the external phase is set to 20 mL / min; after setting the flow rate, the feed pump is turned on to simultaneously introduce the internal phase and the external phase into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid is 150 mm, and the ratio of the sum of the internal and external phase flow rates Q to the receiving height H is 1:7.5 (mL / min:mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped up again. This process is repeated three times to obtain the microbead product. The CV value of the microbeads is 6.73%. See [link to product details]. Figure 6 .

[0059] Example 5 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 97.9% soybean oil, 0.1% blue pigment, and 2% castor oil / IPDI copolymer. The viscosity of the internal phase at room temperature (25℃) is 230 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped up again. This process is repeated three times to obtain the microbead product. The CV value of the microbeads is 13.11%. See [link to product details]. Figure 7 .

[0060] Example 6 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% peppermint oil and 0.1% orange pigment. The viscosity of the internal phase at room temperature (25℃) is 13 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped up again. This process is repeated three times to obtain the microbead product. The CV value of the microbeads is 15.26%. See [link to product details]. Figure 8 .

[0061] Example 7 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 97.5% soybean oil, 0.5% purple fluorescent powder, and 2% castor oil / IPDI copolymer. The viscosity of the internal phase at room temperature (25℃) is 245 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped up again. This process is repeated three times to obtain the microbead product. The CV value of the microbeads is 13.82%. See [link to product details]. Figure 9 .

[0062] Example 8 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 2% castor oil / IPDI copolymer, 2% lecithin, 14% probiotic powder, 0.5% Span 80, and 81.5% soybean oil. The viscosity of the internal phase at room temperature (25℃) is 283 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped up again. This process is repeated three times to obtain the microbead product. The CV value of the microbeads is 16.37%. See [link to product details]. Figure 10 .

[0063] Example 9 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil, 0.1% green pigment. The viscosity of the internal phase at room temperature (25℃) is 53 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; Ceramide moisturizing and repairing essence: Prepare a solution of 0.1% allantoin, 0.3% xanthan gum, 0.03% HA-TP, 2% glycerin, 3% propylene glycol, 0.05% EDTA-2NA, 0.15% methyl ester, 1% trehalose, 0.4% phenoxyethanol, 0.01% AYA03969, 0.05% CO-40, 1% MG liposomes, and the remainder water, and stir well for later use; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and collection: The droplets quickly solidify into shape in the receiving liquid. The solidified beads are picked up, soaked in pure water, stirred slightly, picked up again, and soaked in pure water again. The washing is repeated 3 times to obtain microbeads. The CV value of the microbeads is 7.26%. Preparation of essence: The microbeads are added to the ceramide moisturizing and repairing essence to obtain the moisturizing and repairing microbead essence product.

[0064] Example 10 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil and 0.1% green pigment. The viscosity of the internal phase at room temperature (25℃) is 53 cP; Receiving liquid: Prepare a 1% calcium chloride aqueous solution; Silky soothing shampoo: Prepare a solution of 7.5% sodium lauryl ether sulfate, 3.6% cocamidopropyl betaine, 1% cocamidopropyl DEA, 0.02% citric acid, 1% NaCl, 1% phenoxyethanol and the balance water, stir well and set aside; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and collection: The droplets quickly solidify into shape in the receiving liquid. The solidified beads are picked up, soaked in pure water, stirred slightly, picked up again, and soaked in pure water again. The washing is repeated 3 times to obtain microbeads. The CV value of the microbeads is 6.58%. Shampoo preparation: The microbeads are added to the silky soothing shampoo to obtain the silky soothing microbead shampoo product.

[0065] Example 11 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil and 0.1% green pigment. The viscosity of the internal phase at room temperature (25℃) is 51 cP; Receiving liquid: Prepare a 1% calcium chloride aqueous solution; Soothing and repairing essential oil: Prepare 99.4% jojoba oil, 0.2% Roman chamomile essential oil, 0.2% lavender essential oil, 0.1% blue chamomile essential oil, and 0.1% neroli essential oil by mass, and stir well for later use; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and collection: The droplets quickly solidify into shape in the receiving liquid. The solidified beads are picked up, soaked in pure water, stirred slightly, picked up again, and soaked in pure water again. The washing is repeated 3 times to obtain microbeads. The CV value of the microbeads is 5.63%. Preparation of essential oil: The microbeads are added to the soothing and repairing essential oil to obtain the soothing and repairing microbead essential oil product.

[0066] Example 12 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil and 0.1% green pigment. The viscosity of the internal phase at room temperature (25℃) is 54 cP; Receiving liquid: Prepare a 1% calcium chloride aqueous solution; Milk preparation: Pasteurize and ultra-high temperature sterilize raw milk for later use; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and collection: The droplets quickly solidify into shape in the receiving liquid. The solidified beads are picked up, soaked in pure water, stirred slightly, picked up again, and soaked in pure water again. The washing is repeated 3 times to obtain microbeads. The CV value of the microbeads is 8.39%. Preparation of milk containing microbeads: The microbeads are added to the milk to obtain milk containing microbeads.

[0067] Example 13 This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil and 0.1% orange pigment. The viscosity of the internal phase at room temperature (25℃) is 52 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 5 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 90 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:2.57 (mL / min:mm). (3) Solidification and Collection: The droplets rapidly solidify in the receiving liquid. The solidified beads are then scooped up, immersed in pure water, gently stirred, and then scooped up again. This process is repeated three times to obtain the microbead product. The CV value of the microbeads is 17.21%. See [link to product details]. Figure 11 .

[0068] Comparative Example 1 This comparative example prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil and 0.1% yellow pigment. The viscosity of the internal phase at room temperature (25℃) is 51 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set as follows: external phase 15 mL / min; internal phase 25 mL / min. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:3.75 (mL / min:mm). Figure 12 It can be seen that, since the flow rate ratio of the outer phase to the inner phase is 0.6:1, the outer phase cannot effectively encapsulate the inner phase, and the oil phase in the inner phase is prone to leakage, making it impossible to obtain O / W type microsphere products.

[0069] Comparative Example 2 This comparative example prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil, 0.1% purple pigment. The viscosity of the internal phase at room temperature (25℃) is 52 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 350 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:10.29 (mL / min:mm).

[0070] pass Figure 13It can be seen that when the ratio of the sum of the internal and external phase flow velocities Q to the receiving height H is 1:10.29 (mL / min: mm), the internal oil phase is prone to leakage, and O / W type microsphere products cannot be obtained.

[0071] Table 1 shows the preparation conditions of the microspheres in Examples 1-13. The average particle size and CV value of the microspheres in Examples 1-13 were measured respectively, and the results are shown in Table 2.

[0072]

[0073] Note: - indicates that the microbeads prepared in Example 4 were pure, the internal phase was an aqueous solution of sodium alginate, and the viscosity was not measured.

[0074]

[0075] Table 2 shows that the CV values ​​of the microspheres prepared in Examples 1, 2, 4, 9, 10, 11, and 12 are all less than 10%. When the internal phase is an oil phase, the viscosity of the oil phase has a significant impact on the CV value of the microspheres. In Examples 5-8, the internal phase viscosity was too high or too low, resulting in a larger CV value for the microspheres. The larger CV value in Example 13 is due to the Q / H ratio of 1:2.57, which leads to a larger CV value. In Example 3, the excessively high flow rate ratio between the external and internal phases also led to an increase in the CV value of the sodium alginate microspheres. This indicates that only when the flow rate ratio between the external and internal phases, the Q / H ratio, and the internal phase viscosity are all within specific ranges can microspheres with a CV value of less than 10% be obtained.

[0076] Using the same batch of raw materials, three batches of microbeads were prepared according to the preparation methods in Examples 1, 2, 4, 7, and 8. The CV value of each batch was tested, and the results are shown in Table 3.

[0077]

[0078] Table 3 shows that the microspheres prepared by this invention have high batch stability.

[0079] Example 14 The difference between the microfluidic chip used in this embodiment and that in Embodiment 1 is that the vertical distance D between the bottom surface of the inner phase channel and the plane containing the outlet hole of the outer phase channel is 5mm.

[0080] This embodiment prepares O / W type microspheres, and the preparation method includes the following steps: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil and 0.1% yellow pigment. The viscosity of the internal phase at room temperature (25℃) is 56 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate was set to 30 mL / min for the external phase and 4 mL / min for the internal phase. After setting the flow rate, the feed pump was turned on to simultaneously introduce the internal and external phases into the microfluidic chip to obtain droplets. The height H between the bottom of the chip and the surface of the receiving liquid was 150 mm. The ratio of the sum of the internal and external phase flow rates Q to the receiving height H was 1:4.41 (mL / min: mm). (3) Solidification and collection: The droplets quickly solidify into shape after falling into the receiving liquid. The solidified beads are picked up, soaked in pure water, stirred slightly, picked up again, and soaked in pure water again. This process is repeated 3 times to obtain microbeads.

[0081] pass Figure 14 , Figure 15 It can be seen that leakage of the internal oil phase of the microspheres leads to a decrease in the encapsulation rate and poor uniformity of the obtained microspheres, with multiple encapsulations inside.

[0082] It should be noted that the microfluidic chip of this invention can also be used to prepare O / W type fibers. The specific steps are as follows: (1) Solution preparation: External phase: Prepare a 1% sodium alginate aqueous solution and store it at room temperature for later use; Internal phase: The internal phase contains the following components by mass percentage: 99.9% soybean oil and 0.1% yellow pigment. The viscosity of the internal phase at room temperature (25℃) is 53 cP; Receiving solution: Prepare a 1% calcium chloride aqueous solution; (2) Droplet preparation: The flow rate is set to 30 mL / min for the outer phase and 4 mL / min for the inner phase. After setting the flow rate, the feed pump is turned on to simultaneously introduce the inner and outer phases into the microfluidic chip. The height H between the bottom of the microfluidic chip and the surface of the receiving liquid is 30 mm. The ratio of the sum of the flow rates of the inner and outer phases Q to the receiving height H is 1:0.88 (mL / min: mm) to obtain encapsulated fibers. (3) Solidification and Collection: The encapsulated fibers are rapidly solidified in the receiving liquid. The solidified fibers are then retrieved, immersed in pure water, gently stirred, and then retrieved again. This process is repeated three times to obtain the encapsulated fiber product. See [link to product details]. Figure 16 and Figure 17 .

[0083] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for preparing calcium alginate microbeads, characterized in that, Includes the following steps: (1) Prepare the external phase, internal phase and receiving liquid separately; the external phase is an aqueous phase, and the aqueous phase includes sodium alginate; (2) The inner phase and the outer phase are simultaneously introduced into the microfluidic chip to obtain microdroplets; the microfluidic chip includes an outer phase channel and an inner phase channel, the inner phase channel is located inside the outer phase channel, and the bottom of the outer phase channel is provided with an outlet hole; the vertical distance between the bottom surface of the inner phase channel and the plane where the outlet hole of the outer phase channel is located is D, where D is 0.5-5mm; the microfluidic chip is located above the receiving liquid; the vertical distance between the plane where the outlet hole of the outer phase channel is located and the liquid surface of the receiving liquid is H, where H is 50-300mm; the flow rate of the inner phase is 0.1-100mL / min; the flow rate ratio of the outer phase to the inner phase is (1-20):1; the inner phase is an oil phase or the inner phase is an aqueous phase containing sodium alginate, and when the inner phase is an oil phase, the viscosity of the inner phase at room temperature is 5-300 cP; (3) The microdroplets fall into the receiving liquid, solidify and form a shape, are picked up, washed and obtained calcium alginate microbeads.

2. The method for preparing calcium alginate microbeads according to claim 1, characterized in that, The focusing angle between the lower side of the outer phase pipe and the plane containing the outlet hole of the outer phase pipe is θ, and the focusing angle θ is 0-70°.

3. The method for preparing calcium alginate microbeads according to claim 2, characterized in that, The focusing angle between the lower side of the outer phase pipe and the plane where the outlet hole of the outer phase pipe is located is θ, where θ is 15-50°.

4. The method for preparing calcium alginate microbeads according to claim 1, characterized in that, The inner phase pipe is cylindrical, and its inner diameter is 0.6-3mm.

5. The method for preparing calcium alginate microbeads according to claim 1, characterized in that, The diameter of the outlet hole is 0.6-2mm.

6. The method for preparing calcium alginate microbeads according to claim 1, characterized in that, The vertical distance between the bottom surface of the inner phase pipe and the plane containing the outlet hole of the outer phase pipe is D, where D is 1-2 mm.

7. The method for preparing calcium alginate microbeads according to claim 1, characterized in that, The vertical distance between the plane of the outlet hole of the external phase pipe and the surface of the receiving liquid is H, where H is 100-260mm.

8. The method for preparing calcium alginate microbeads according to claim 1, characterized in that, The flow rate ratio of the external phase to the internal phase is (2-10):

1.

9. A type of calcium alginate microbeads, characterized in that, The microspheres are prepared by the preparation method according to any one of claims 1-8.

10. The application of microbeads prepared by the method according to any one of claims 1-8, characterized in that, The microbeads are used to prepare cosmetics, food, or textiles and clothing.

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