A method for preparing an oil bead with enhanced vesicle stability, and products and uses thereof

Abstract

The application provides a preparation method of oil condensation beads with enhanced vesicle stability, and products and applications thereof, and the method comprises the following steps: injecting a shearing phase, an outer oil phase and an inner water phase into outer, middle and inner channels of a tri-axial microfluidic device respectively, adjusting the flow rates of the three phases, shearing, and solidifying to obtain the oil condensation beads; components of the shearing phase include a shearing agent and water; components of the outer oil phase include an oily gel agent and an emollient oil; the oily gel agent includes any one of HDI / trihydroxymethyl hexyl lactone cross-linked polymer, polyamide-8, castor oil / IPDI copolymer, dibutyl ethyl hexanoyl glutamine or dibutyl lauryl glutamine or a combination of at least two of the above; components of the inner water phase include vesicles, polyhydric alcohol and water. The method can enable the vesicles to maintain good stability at-15 DEG C to 48 DEG C, get rid of cold chain dependency, and achieve normal temperature preservation.

Description

Technical Field

[0001] This invention belongs to the field of cosmetics and pharmaceutical delivery, specifically relating to a method for preparing oil beads that enhance vesicle stability, as well as the product and its application. Background Technology

[0002] Vesicles, as key mediators of intercellular communication, are rich in bioactive molecules such as microRNA, proteins, and lipids, showing great potential in fields such as cosmetics, regenerative medicine, tumor diagnosis and treatment, and drug delivery. However, the membrane structure of vesicles is extremely sensitive to the environment. Traditional freeze-drying can cause membrane rupture, and freezing at -15°C can produce ice crystals that cause damage, significantly reducing their activity. Therefore, the high cost of transporting vesicles severely limits their translational applications.

[0003] CN113750243A discloses a protective agent for improving vesicle stability, which is prepared by dissolving one or more of the following components in a concentrated saline suspension of vesicles: 0.5-5% albumin, 1-5% hydroxypropyl-β-cyclodextrin, and 0.02-0.2% poloxamer 188, where the percentages represent the final concentrations of each component in the vesicle-containing saline suspension. The vesicle solution with the added protective agent remained stable after 7 days at 4°C, and the number of vesicles and the amount of drug encapsulated were significantly greater than those in the control group without the protective agent. The chemotactic effect on neutrophils and the killing effect on A549 tumor cells were comparable to those of freshly prepared drug-loaded vesicles.

[0004] Conventional vesicle applications use vesicles as carriers to transport substances, but encapsulation technologies that protect the vesicle structure are relatively rare, and the addition of additional protective agents can easily lead to sedimentation and aggregation. Therefore, there is an urgent need to develop an encapsulation technology that can maintain the integrity of the vesicle structure and protect the active ingredients inside, while also providing a visually distinctive appearance to enhance the aesthetics of cosmetics. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a method for preparing oil beads that enhance vesicle stability, as well as the product and application thereof. The method of the present invention enables vesicles to maintain good stability at temperatures ranging from -15℃ to 48℃, eliminating dependence on cold chains and achieving room temperature storage.

[0006] To achieve this objective, the present invention adopts the following technical solution: In a first aspect, the present invention provides a method for preparing oil beads that enhance vesicle stability, the method comprising: injecting a shear phase, an outer oil phase, and an inner water phase into the outer, middle, and inner channels of a three-phase coaxial microfluidic device, respectively; adjusting the three-phase flow rates; performing shearing; and solidifying to obtain the oil beads. The components of the shear phase include a shearing agent and water; The components of the outer oil phase include an oily gelling agent and moisturizing oils; the oily gelling agent includes any one or a combination of at least two of HDI / trimethylolhexyl lactone crosspolymer, polyamide-8, castor oil / IPDI copolymer, butyl ethylhexanoyl glutamine, or butyl lauroyl glutamine. The components of the internal aqueous phase include vesicles, polyols, and water.

[0007] This invention constructs a multi-level microcapsule system using microfluidic technology. The outer oil phase component forms a dense protective barrier around the vesicles, isolating oxygen and reducing damage caused by shear forces. The shear phase with a certain viscosity blocks the transfer of oxygen and temperature, maintaining the property and morphological stability of the outer oil phase and preventing property changes caused by external factors during transportation and long-term storage. The polyol in the inner aqueous phase can provide osmotic pressure for the vesicle structure, and the viscous system reduces the collision of free electrons with the vesicle structure. Under the above factors, the vesicles maintain good stability at temperatures ranging from -15℃ to 48℃, eliminating cold chain dependence and enabling room temperature storage.

[0008] Preferably, the mass ratio of shearing agent to water in the shear phase is (0.5-5):(95-99.5).

[0009] The specific point values ​​in (0.5-5) can be 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 3, 4 or 5, etc.

[0010] The specific point values ​​in (95-99.5) can be 95, 95.5, 96, 96.5, 97, 97.5, 98, 98.5, 99, or 99.5, etc.

[0011] Preferably, the mass ratio of oily gelling agent to moisturizing oil in the outer oil phase is (10-20):(80-90).

[0012] The specific point values ​​in (10-20) can be 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, etc.

[0013] The specific point values ​​in (80-90) can be 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 or 90, etc.

[0014] Preferably, the ratio of vesicles, polyols, and water in the internal aqueous phase is 1×(10) 5 -10 15 ) each: (5-25) g: (75-95) g.

[0015] (10 5 -10 15 The specific point value in ) can be 10 510 6 10 7 10 8 10 9 10 10 10 11 10 12 10 13 10 14 Or 10 15 wait.

[0016] The specific point values ​​in (5-25) can be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25, etc.

[0017] The specific point values ​​in (75-95) can be 75, 76, 77, 78, 79, 80, 85, 90, 91, 92, 93, 94 or 95, etc.

[0018] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0019] Preferably, the flow rate of the shear phase is 10-30 mL / min, for example, it can be 10 mL / min, 12 mL / min, 15 mL / min, 17 mL / min, 20 mL / min, 23 mL / min, 25 mL / min, 28 mL / min or 30 mL / min, etc.

[0020] Preferably, the flow rate of the external oil phase is 1-3 mL / min, for example, it can be 1 mL / min, 1.2 mL / min, 1.5 mL / min, 1.7 mL / min, 2 mL / min, 2.3 mL / min, 2.5 mL / min, 2.8 mL / min or 3 mL / min, etc.

[0021] Preferably, the flow rate of the internal aqueous phase is 0.2-0.8 mL / min, for example, it can be 0.2 mL / min, 0.25 mL / min, 0.3 mL / min, 0.35 mL / min, 0.4 mL / min, 0.45 mL / min, 0.5 mL / min, 0.55 mL / min, 0.6 mL / min, 0.65 mL / min, 0.7 mL / min, 0.75 mL / min or 0.8 mL / min, etc.

[0022] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0023] In this invention, the flow rates of the shear phase, outer oil phase, and inner water phase are within the above-mentioned range, which can control the outer oil phase coating layer within a reasonable range and achieve protection of the inner water phase vesicles.

[0024] Preferably, the shearing temperature is 60-70℃, for example, it can be 60℃, 61℃, 62℃, 63℃, 64℃, 65℃, 66℃, 67℃, 68℃, 69℃ or 70℃, etc.

[0025] Preferably, the curing temperature is 20-30℃, for example, it can be 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃ or 30℃.

[0026] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0027] Preferably, the inner diameter of the outer channel is 3.45-3.55 mm, for example, it can be 3.45 mm, 3.46 mm, 3.47 mm, 3.48 mm, 3.49 mm, 3.5 mm, 3.51 mm, 3.52 mm, 3.53 mm, 3.54 mm or 3.55 mm, etc.; and the length is 219.5-220.5 mm, for example, it can be 219.5 mm, 219.6 mm, 219.7 mm, 219.8 mm, 219.9 mm, 220 mm, 220.1 mm, 220.2 mm, 220.3 mm, 220.4 mm or 220.5 mm, etc.

[0028] Preferably, the inner diameter of the middle channel is 2.25-2.35 mm, for example, 2.25 mm, 2.26 mm, 2.27 mm, 2.28 mm, 2.29 mm, 2.30 mm, 2.31 mm, 2.32 mm, 2.33 mm, 2.34 mm or 2.35 mm; and the length is 29.5-30.5 mm, for example, 29.5 mm, 29.6 mm, 29.7 mm, 29.8 mm, 29.9 mm, 30 mm, 30.1 mm, 30.2 mm, 30.3 mm, 30.4 mm or 30.5 mm.

[0029] Preferably, the inner diameter of the inner channel is 0.8-0.9 mm, for example, it can be 0.8 mm, 0.81 mm, 0.82 mm, 0.83 mm, 0.84 mm, 0.85 mm, 0.86 mm, 0.87 mm, 0.88 mm, 0.89 mm or 0.9 mm; and the length is 39.5-40.5 mm, for example, it can be 39.5 mm, 39.6 mm, 39.7 mm, 39.8 mm, 39.9 mm, 40 mm, 40.1 mm, 40.2 mm, 40.3 mm, 40.4 mm or 40.5 mm.

[0030] Preferably, the wall thickness of the outer channel, the middle channel and the inner channel is 0.35-0.45 mm, for example, it can be 0.35 mm, 0.36 mm, 0.37 mm, 0.38 mm, 0.39 mm, 0.4 mm, 0.41 mm, 0.42 mm, 0.43 mm, 0.44 mm or 0.45 mm.

[0031] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0032] Preferably, the oily gelling agent comprises HDI / trimethylolhexyl lactone crosspolymer, polyamide-8, and dibutylethylhexanoyl glutamine.

[0033] The preferred combination of HDI / trimethylolhexyl lactone crosspolymer, polyamide-8, and dibutylethylhexanoyl glutamine has a synergistic effect and provides better protection for vesicles.

[0034] Preferably, the mass ratio of the HDI / trimethylolhexyl lactone crosspolymer, polyamide-8, and dibutylethylhexanoyl glutamine is (1-5):(1-5):(1-5).

[0035] The specific point values ​​in the first (1-5) can be 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5, etc.

[0036] The specific point values ​​in the second (1-5) can be 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5, etc.

[0037] The specific point values ​​in the third (1-5) can be 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5, etc.

[0038] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0039] Preferably, the shearing agent comprises any one or a combination of at least two of the following: acrylate / C10-30 alkanol acrylate crosspolymer, carbomer, polyvinyl alcohol, or glycerol.

[0040] Preferably, the shearing agent comprises acrylate / C10-30 alkanol acrylate crosspolymer, carbomer, and polyvinyl alcohol.

[0041] The preferred combination is an acrylic (ester) cross-linked polymer / C10-30 alkanol acrylate, carbomer, and polyvinyl alcohol. The three have a synergistic effect, better shear stability, and control of the outer oil phase coating layer within a reasonable range, thus providing better protection for the vesicles.

[0042] Preferably, the mass ratio of the acrylate / C10-30 alkanol acrylate crosspolymer, carbomer, and polyvinyl alcohol is (0.1-0.5):(0.1-0.5):(1-5).

[0043] The specific point values ​​in the first (0.1-0.5) can be 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45 or 0.5, etc.

[0044] The specific point values ​​in the second (0.1-0.5) can be 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45 or 0.5, etc.

[0045] The specific point values ​​in (1-5) can be 1, 1.2, 1.5, 1.7, 2, 2.3, 2.5, 2.8, 3, 3.5, 4, 4.5 or 5, etc.

[0046] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0047] Preferably, the moisturizing oil comprises any one or a combination of at least two of the following: triglyceride (acetylated hexanoate), tocopheryl acetate, meadowfoam seed oil, isononyl isononanoate, caprylic / capric triglyceride, tocopherol, squalane, sunflower seed oil, macadamia nut oil, jojoba seed oil, diisostearyl malate, hydrogenated polyisobutylene, or dextrin palmitate.

[0048] Preferably, the vesicles include any one or a combination of at least two of the following: plant-derived vesicles, animal-derived vesicles, or microbial-derived vesicles.

[0049] All types of vesicles commonly used in this field are applicable to this invention, including but not limited to grape vesicles, probiotic vesicles, or mesenchymal stem cell secretory vesicles.

[0050] Preferably, the polyol comprises any one or a combination of at least two of the following: ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, 1,2-hexanediol, 1,6-hexanediol, glycerol, octanediol, 1,9-nonanediol, or 1,10-decanediol.

[0051] In a second aspect, the present invention provides oil beads prepared by the method described in the first aspect.

[0052] Preferably, the oil beads have a particle size of 0.5-5 mm, for example, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 2 mm, 3 mm, 4 mm or 5 mm.

[0053] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0054] Thirdly, the present invention provides the application of oil beads as described in the second aspect in cosmetics.

[0055] Compared with the prior art, the present invention has the following beneficial effects: This invention constructs a multi-level microcapsule system using microfluidic technology. The outer oil phase component forms a dense protective barrier around the vesicles, isolating oxygen and reducing damage caused by shear forces. The shear phase with a certain viscosity blocks the transfer of oxygen and temperature, maintaining the property and morphological stability of the outer oil phase and preventing property changes caused by external factors during transportation and long-term storage. The polyol in the inner aqueous phase can provide osmotic pressure for the vesicle structure, and the viscous system reduces the collision of free electrons with the vesicle structure. Under the above factors, the vesicles maintain good stability at temperatures ranging from -15℃ to 48℃, eliminating cold chain dependence and enabling room temperature storage. Detailed Implementation

[0056] To further illustrate the technical means and effects of the present invention, the following describes the technical solution of the present invention in conjunction with preferred embodiments of the present invention. However, the present invention is not limited to the scope of the embodiments.

[0057] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0058] The sources of the devices and materials used in the following specific embodiments are as follows: Three coaxial microfluidic devices: outer channel with an inner diameter of 3.5 mm, a length of 220 mm, and a wall thickness of 0.4 mm; middle channel with an inner diameter of 2.3 mm, a length of 30 mm, and a wall thickness of 0.4 mm; inner channel with an inner diameter of 0.86 mm, a length of 40 mm, and a wall thickness of 0.4 mm.

[0059] Grape vesicles: Take 100 g of fresh grapes and add them to 100 mL of sterile PBS buffer to homogenize. Centrifuge at 3000 g for 10 min at 4℃ to remove larger residues. Take the upper purple transparent solution and centrifuge at 10000 g for 40 min at 4℃. Take the supernatant and centrifuge at 120000 g for 60 min at 4℃. Resuspend the precipitate in 1 mL of sterile PBS buffer. Centrifuge at 120000 g for 60 min at 4℃ and resuspend the precipitate in 1 mL of sterile PBS buffer. Filter through a 0.45 μm filter membrane and a 0.22 μm filter membrane sequentially to obtain the vesicles.

[0060] Acrylic (ester) / C10-30 alkanol acrylate crosspolymers were purchased from Lubrizol Specialty Chemicals Manufacturing (Shanghai) Co., Ltd.; carbomer was purchased from Lubrizol Specialty Chemicals Manufacturing (Shanghai) Co., Ltd.; polyvinyl alcohol was purchased from Guangzhou Lilong Daily Chemical Co., Ltd.; HDI / trimethylolhexyl lactone crosspolymer was purchased from Lubrizol Specialty Chemicals Manufacturing (Shanghai) Co., Ltd.; polyamide-8 was purchased from Croda Chemicals (Shanghai) Co., Ltd.; dibutylethylhexanoyl glutamine was purchased from Croda Chemicals (Shanghai) Co., Ltd.

[0061] Example 1 This embodiment provides a method for preparing oil beads, the method comprising: A shear phase was prepared by uniformly mixing 0.15 g of acrylate / C10-30 alkyl acrylate crosspolymer, 0.15 g of carbomer, 2.7 g of polyvinyl alcohol, and 97 g of water. An external oil phase was prepared by uniformly mixing 5 g of HDI / trimethylolhexyl lactone crosspolymer, 5 g of polyamide-8, 5 g of dibutylethylhexanoyl glutamine, and 85 g of isononyl isononanoate. (1×10⁻⁶) 10 The inner aqueous phase was prepared by uniformly mixing 1 grape vesicles, 15 g of 1,2-propanediol and 85 g of water.

[0062] Shear phase, external oil phase, and internal water phase were injected into the outer, middle, and inner channels of a three-phase coaxial microfluidic device, respectively. The flow rates of the three phases were adjusted as follows: shear phase 20 mL / min, external oil phase 2 mL / min, and internal water phase 0.5 mL / min. Shearing was performed at 65℃ and solidification was performed at 25℃ to obtain oil beads.

[0063] Example 2 This embodiment provides a method for preparing oil beads, the method comprising: A shear phase was prepared by uniformly mixing 0.05 g of acrylate / C10-30 alkanol acrylate crosspolymer, 0.05 g of carbomer, 0.5 g of polyvinyl alcohol, and 99.4 g of water. An external oil phase was prepared by uniformly mixing 6 g of HDI / trimethylolhexyl lactone crosspolymer, 8 g of polyamide-8, 6 g of dibutylethylhexanoyl glutamine, and 80 g of tocopheryl acetate. (1×10) 15 The inner aqueous phase was prepared by uniformly mixing 1 grape vesicle, 20 g of 1,2-butanediol and 95 g of water.

[0064] Shear phase, external oil phase, and internal water phase were injected into the outer, middle, and inner channels of a three-phase coaxial microfluidic device, respectively. The flow rates of the three phases were adjusted as follows: shear phase 10 mL / min, external oil phase 1 mL / min, and internal water phase 0.2 mL / min. Shearing was performed at 60℃ and solidification was performed at 20℃ to obtain oil beads.

[0065] Example 3 This embodiment provides a method for preparing oil beads, the method comprising: A shear phase was prepared by uniformly mixing 0.1 g of acrylate / C10-30 alkanol acrylate crosspolymer, 0.4 g of carbomer, 4.5 g of polyvinyl alcohol, and 95 g of water. An external oil phase was prepared by uniformly mixing 3 g of HDI / trimethylolhexyl lactone crosspolymer, 3 g of polyamide-8, 4 g of dibutylethylhexanoyl glutamine, and 90 g of squalane. (1×10⁻⁶) 5 The inner aqueous phase was prepared by mixing 1 grape vesicle, 5 g of 1,2-pentanediol and 75 g of water.

[0066] Shear phase, external oil phase, and internal water phase were injected into the outer, middle, and inner channels of a three-phase coaxial microfluidic device, respectively. The flow rates of the three phases were adjusted as follows: shear phase 30 mL / min, external oil phase 3 mL / min, and internal water phase 0.8 mL / min. Shearing was performed at 70℃ and solidification was performed at 30℃ to obtain oil beads.

[0067] Example 4 This embodiment provides a method for preparing oil beads, which differs from Example 1 only in that: HDI / trimethylolhexyl lactone crosslinking polymer is not added to the external oil phase, and the reduced amount is proportionally allocated to polyamide-8 and dibutyl ethylhexanoyl glutamine, while the remaining steps remain unchanged.

[0068] Example 5 This embodiment provides a method for preparing oil beads, which differs from Example 1 only in that: polyamide-8 is not added to the external oil phase, and its reduced amount is proportionally allocated to HDI / trimethylolhexyl lactone crosslinking polymer and dibutyl ethylhexanoyl glutamine, while the remaining steps remain unchanged.

[0069] Example 6 This embodiment provides a method for preparing oil beads, which differs from Example 1 only in that: dibutyl ethylhexanoyl glutamine is not added to the external oil phase, and its reduced amount is proportionally allocated to the HDI / trimethylolhexyl lactone crosslinking polymer and polyamide-8, while the other steps remain unchanged.

[0070] Example 7 This embodiment provides a method for preparing oil beads, which differs from Example 1 only in that: no acrylate / C10-30 alkanol acrylate crosslinking polymer is added to the shear phase, and the reduced amount is proportionally allocated to carbomer and polyvinyl alcohol, while the remaining steps remain unchanged.

[0071] Example 8 This embodiment provides a method for preparing oil beads, which differs from Example 1 only in that: no carbomer is added to the shear phase, and its reduction is proportionally allocated to the acrylate / C10-30 alkanol acrylate crosslinking polymer and polyvinyl alcohol, while the other steps remain unchanged.

[0072] Example 9 This embodiment provides a method for preparing oil beads, which differs from Example 1 only in that: polyvinyl alcohol is not added to the shear phase, and its reduction is proportionally allocated to the acrylate / C10-30 alkanol acrylate crosslinking polymer and carbomer, while the other steps remain unchanged.

[0073] Example 10 This embodiment provides a method for preparing oil beads, which differs from Example 1 only in that "shear phase 20 mL / min, outer oil phase 2 mL / min, inner aqueous phase 0.5 mL / min" is replaced with "shear phase 5 mL / min, outer oil phase 0.5 mL / min, inner aqueous phase 0.1 mL / min", while the other steps remain unchanged.

[0074] Example 11 This embodiment provides a method for preparing oil beads, which differs from Example 1 only in that "shear phase 20 mL / min, outer oil phase 2 mL / min, inner aqueous phase 0.5 mL / min" is replaced with "shear phase 35 mL / min, outer oil phase 3.5 mL / min, inner aqueous phase 1 mL / min", while the other steps remain unchanged.

[0075] Comparative Example 1 This comparative example provides a method for preparing oil beads, the method comprising: A shear phase was prepared by uniformly mixing 0.15 g of acrylate / C10-30 alkyl acrylate crosspolymer, 0.15 g of carbomer, 2.7 g of polyvinyl alcohol, and 97 g of water. An external oil phase was prepared by uniformly mixing 5 g of HDI / trimethylolhexyl lactone crosspolymer, 5 g of polyamide-8, 5 g of dibutylethylhexanoyl glutamine, and 85 g of isononyl isononanoate. (5×10) 11 The inner aqueous phase was prepared by uniformly mixing 1 grape vesicles, 15 g of 1,2-propanediol and 85 g of water.

[0076] The inner aqueous phase was added to the outer oil phase and stirred at 3000 rpm for 5 min; then the above mixture was added to the shear phase and stirred at 3000 rpm for 5 min at 65°C, and then solidified at 25°C to obtain oil beads.

[0077] Test Example 1 Oil beads prepared in Examples 1-11 and Comparative Example 1 were subjected to different treatments. The stability was evaluated by detecting changes in particle size and the number of grape-like vesicles before and after treatment. Three parallel samples were set up for each group, and the average value was taken. The average change in oil bead size (mm) = average oil bead size after treatment - average oil bead size before treatment; the change in vesicle number = log... 10 (Initial number of vesicles) - log 10 (Final number of vesicles)

[0078] As shown in Tables 1-2, and as demonstrated in Examples 1-3, this invention constructs a multi-level microcapsule system using microfluidic technology. The outer oil phase component forms a dense protective barrier around the vesicles, isolating oxygen and reducing damage. The vesicles maintain good stability at temperatures ranging from -15℃ to 48℃, eliminating cold chain dependence and enabling room temperature storage. The average oil droplet size distribution is 1.5-2.3 mm. Examples 4-6 show that the HDI / trimethylolhexyl lactone crosslinker, polyamide-8, and dibutylethylhexanoyl glutamine in the oily gelling agent have a synergistic effect, providing better protection for the vesicles. Examples 7-9 show that the acrylate / C10-30 alkanol acrylate crosslinker, carbomer, and polyvinyl alcohol in the shearing agent have a synergistic effect, exhibiting better shear stability and providing better protection for the vesicles. Examples 10-11 show that the flow rate range of the shear phase, outer oil phase, and inner aqueous phase affects the protective effect on the inner aqueous phase vesicles. As shown in Comparative Example 1, microfluidic technology can achieve precise control of vesicle encapsulation compared to the traditional emulsion method, thereby improving the stability of oil beads.

[0079] Table 1 Table 2 Test Example 2 Oil beads prepared in Examples 1-11 and Comparative Example 1 were placed in centrifuge tubes and centrifuged at 727 g for 30 min. The ability to resist external damage was evaluated by the changes in the state of the samples before and after centrifugation and the changes in the particle size of the oil beads. Three parallel samples were set up for each group, and the average value of the results was taken. The average change in the particle size of oil beads (mm) = the average particle size of oil beads after treatment - the average particle size of oil beads before treatment.

[0080] As shown in Table 3, Examples 1-3 demonstrate that the present invention constructs a multi-level microcapsule system using microfluidic technology. The outer oil phase component forms a dense protective barrier around the vesicles, reducing damage caused by shear force and resulting in good vesicle stability. Examples 4-6 show that the HDI / trimethylolhexyl lactone crosslinking polymer, polyamide-8, and dibutylethylhexanoyl glutamine in the oily gelling agent have a synergistic effect, enhancing the ability of the oil beads to resist external damage. Examples 7-9 show that the acrylate / C10-30 alkanol acrylate crosslinking polymer, carbomer, and polyvinyl alcohol in the shearing agent have a synergistic effect, enhancing the ability of the oil beads to resist external damage. Examples 10-11 show that the flow rate range of the shear phase, outer oil phase, and inner aqueous phase affects the ability of the oil beads to resist external damage. Comparative Example 1 shows that microfluidic technology, compared to the traditional emulsion method, can achieve precise control of vesicle encapsulation, enhancing the ability of the oil beads to resist external damage.

[0081] Table 3 Test Example 3 The VISIA skin analyzer is an instrument capable of quantitatively analyzing the pathological characteristics of the skin. Utilizing advanced optical imaging, RBX, and software technology, it instantly measures and analyzes epidermal spots, pores, wrinkles, and skin texture, as well as subcutaneous vascular and pigmentary lesions caused by ultraviolet radiation, such as porphyrins (oil), brown spots, and erythema, revealing potential risks such as melasma, acne, rosacea, and spider vein malformations. Furthermore, VISIA provides the most comprehensive skin analysis globally, analyzing and diagnosing various skin problems. It measures eight major skin health indices, provides a wealth of first-hand clinical data, and utilizes internationally authoritative skin databases, making diagnostic results more reliable.

[0082] Test samples were prepared using oil beads from Examples 1-11 and Comparative Example 1: 3 wt% oil beads from Examples 1-11 or Comparative Example 1, 0.15 wt% acrylate / C10-30 alkanol acrylate crosslinking polymer, 16 wt% carbomer, 2 wt% polyvinyl alcohol and 78.85 wt% water, and mixed evenly.

[0083] The subjects were healthy Chinese men and women aged 25-60 years with dry, rough facial skin, large pores, poor barrier function, loose facial skin, and lack of elasticity. They were randomly assigned to groups of 5 subjects each. Subjects applied the test sample to their faces twice daily, morning and evening, without using any other cosmetics. Before sample application and on days 1, 7, and 28 after sample application, the subjects' skin pore condition was measured using the VISIA skin analyzer. The change rate of pore area percentage and the change rate of pore number were calculated, and the average of the results for each group was taken. The change rate of pore area percentage (%) = (pore area percentage after sample application - pore area percentage before sample application) / pore area percentage before sample application × 100; the change rate of pore number (%) = (pore number after sample application - pore number before sample application) / pore number before sample application × 100.

[0084] As shown in Tables 4-5, Examples 1-3 demonstrate that the oil-gel beads of the present invention exhibit excellent pore-improving effects, significantly reducing the pore area ratio and the number of pores. Examples 4-6 show that the HDI / trimethylolhexyl lactone crosslinking polymer, polyamide-8, and dibutylethylhexanoyl glutamine in the oily gel have a synergistic effect, providing better protection for vesicles and enhancing the pore-improving effect. Examples 7-9 show that the acrylate / C10-30 alkanol acrylate crosslinking polymer, carbomer, and polyvinyl alcohol in the shearing agent have a synergistic effect, providing better protection for vesicles and enhancing the pore-improving effect. Examples 10-11 show that the flow rate range of the shear phase, the outer oil phase, and the inner aqueous phase affects the vesicle protection effect, and thus the pore-improving effect. Comparative Example 1 shows that microfluidic technology, compared to the traditional emulsion method, can achieve precise control of vesicle encapsulation, improving the vesicle protection effect.

[0085] Table 4 Table 5 This invention illustrates, through the above embodiments, a method for preparing oil beads that enhance vesicle stability, as well as the product and its application. However, this invention is not limited to the above embodiments, meaning that this invention does not necessarily rely on the above embodiments for implementation. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the product, addition of auxiliary components, and selection of specific methods, etc., all fall within the protection and disclosure scope of this invention.

[0086] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0087] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A method for preparing oil beads that enhance vesicle stability, characterized in that, The method includes: injecting a shear phase, an outer oil phase, and an inner water phase into the outer, middle, and inner channels of a three-phase coaxial microfluidic device, respectively; adjusting the three-phase flow rates; performing shearing; and solidifying to obtain the oil beads. The components of the shear phase include a shearing agent and water; The components of the outer oil phase include an oily gelling agent and moisturizing oils; the oily gelling agent includes any one or a combination of at least two of HDI / trimethylolhexyl lactone crosspolymer, polyamide-8, castor oil / IPDI copolymer, butyl ethylhexanoyl glutamine, or butyl lauroyl glutamine. The components of the internal aqueous phase include vesicles, polyols, and water.

2. The method according to claim 1, characterized in that, The mass ratio of shearing agent to water in the shear phase is (0.5-5):(95-99.5); Preferably, the mass ratio of oily gelling agent to moisturizing oil in the outer oil phase is (10-20):(80-90); Preferably, the ratio of vesicles, polyols, and water in the internal aqueous phase is 1×(10) 5 -10 15 ) each: (5-25) g: (75-95) g.

3. The method according to claim 1 or 2, characterized in that, The flow rate of the shear phase is 10-30 mL / min; Preferably, the flow rate of the external oil phase is 1-3 mL / min; Preferably, the flow rate of the internal aqueous phase is 0.2-0.8 mL / min.

4. The method according to any one of claims 1-3, characterized in that, The shearing temperature is 60-70℃.

5. The method according to any one of claims 1-4, characterized in that, The oily gelling agent includes HDI / trimethylolhexyl lactone crosspolymer, polyamide-8, and dibutylethylhexanoyl glutamine; Preferably, the mass ratio of the HDI / trimethylolhexyl lactone crosspolymer, polyamide-8, and dibutylethylhexanoyl glutamine is (1-5):(1-5):(1-5).

6. The method according to any one of claims 1-5, characterized in that, The shearing agent includes any one or a combination of at least two of the following: acrylate / C10-30 alkanol acrylate crosspolymers, carbomer, polyvinyl alcohol, or glycerol; Preferably, the shearing agent comprises an acrylate / C10-30 alkanol acrylate crosspolymer, carbomer, and polyvinyl alcohol; Preferably, the mass ratio of the acrylate / C10-30 alkanol acrylate crosspolymer, carbomer, and polyvinyl alcohol is (0.1-0.5):(0.1-0.5):(1-5).

7. The method according to any one of claims 1-6, characterized in that, The moisturizing oil includes any one or a combination of at least two of the following: triglyceride (acetylated hexanoate), tocopheryl acetate, meadowfoam seed oil, isononyl isononanoate, caprylic / capric triglyceride, tocopherol, squalane, sunflower seed oil, macadamia nut oil, jojoba seed oil, diisostearyl malate, hydrogenated polyisobutylene, or dextrin palmitate. Preferably, the polyol comprises any one or a combination of at least two of the following: ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, 1,2-hexanediol, 1,6-hexanediol, glycerol, octanediol, 1,9-nonanediol, or 1,10-decanediol.

8. Oil beads prepared by the method according to any one of claims 1-7.

9. The oil beads according to claim 8, characterized in that, The oil droplets have a particle size of 0.5-5 mm.

10. The application of the oil beads according to claim 8 or 9 in cosmetics.

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