Vitamin c-coated submicron double emulsion prepared by using ultrasonic microreactor at high flux, microcapsule and preparation method thereof
By preparing submicron-scale dual emulsions using an ultrasonic microreactor and introducing a specific thickener, the problems of stability and encapsulation efficiency of dual emulsions were solved, achieving efficient and stable encapsulation and sustained release of vitamin C.
Patent Information
- Application Number
- CN202510967787.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-14
- Publication Date
- 2025-11-07
AI Technical Summary
Existing methods for preparing double emulsions suffer from wide droplet size distribution, low encapsulation efficiency, and insufficient stability. In particular, the instability of vitamin C in water limits its application in cosmetics and other fields.
A submicron-scale dual emulsion was prepared by using an ultrasonic microreactor combined with ultrasonic emulsification and utilizing the ultrasonic cavitation effect. Konjac glucomannan was introduced as an inner aqueous phase thickener, castor oil/IPDI copolymer as an oil phase thickener, and vitamin E as an inner aqueous phase protectant to optimize the composition of the inner and outer aqueous phases and improve stability.
The prepared dual emulsion has a particle size of 800nm-1.5μm and good stability. After 6 months, the effective substance only decreased by 30%, and after freeze-drying, the effective substance of the microcapsules only decreased by 10%, which significantly improved the stability and encapsulation efficiency of vitamin C.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of emulsion preparation, and particularly relates to a high-throughput preparation of sub-micron double emulsion coated with vitamin C using an ultrasonic microreactor, microcapsules and a preparation method thereof. BACKGROUND
[0002] Vitamin C (ascorbic acid, Vc) is well known for its potent antioxidant properties, its ability to promote collagen synthesis and skin whitening and lightening. Due to its significant biological activity, Vc is often used in various cosmetic and pharmaceutical formulations. However, the instability of vitamin C, especially in water, limits its application in many formulation products. Exposed to light, oxygen and high temperature conditions, Vc will rapidly degrade, resulting in a decrease in its efficacy in various products. Therefore, the development of stable and effective Vc encapsulation delivery technology is essential to maximize its potential benefits in cosmetics.
[0003] Double emulsions, particularly water-in-oil-in-water (W1 / O / W2) emulsions, have become promising carriers for encapsulating hydrophilic active ingredients such as Vc. These emulsions can effectively enhance the stability of the encapsulated substances by providing a protective oil phase barrier around the inner water phase. In addition, double emulsions can also achieve the slow release effect of active ingredients, making them attractive in the fields of cosmetics, food and pharmaceuticals. However, achieving uniform droplet dispersion, high encapsulation efficiency and long-term stability remains a challenge for double emulsions. The traditional technique for preparing double emulsions is high-speed homogenization method, which disperses droplets into emulsions by high-pressure mechanical stirring, thus usually resulting in a wide droplet size distribution and limited encapsulation efficiency.
[0004] And the components of the inner water phase, oil phase and outer water phase in the existing double emulsion encapsulation technology need to be further optimized to improve the stability of the double emulsion.
[0005] Therefore, improving the encapsulation technology of double emulsions and optimizing the component formula design of the inner water phase, oil phase and outer water phase to improve the stability of the double emulsion is a technical problem that needs to be solved by the present application. SUMMARY
[0006] To solve the above technical problems, the purpose of the present application is to provide a kind of high-throughput preparation of coated vitamin c submicron double emulsion using ultrasonic microreactor and its preparation method, the present application is based on ultrasonic emulsification method and water, oil phase gelification, utilize the supermixing ability of ultrasonic pipeline reactor, the cavitation bubble generated by ultrasonic wave through cavitation effect grows and collapses in liquid, form local high-energy explosion, can be extremely effective to reduce the particle size of droplet and realize more uniform emulsification effect, with smaller and more uniform double emulsion structure obtain more long-term stability;At the same time, introduce konjac glucomannan (KGM) as internal water phase thickening agent significantly enhance stability, thereby significantly inhibit the migration and release of vitamin C, introduce castor oil / IPDI copolymer as oil phase thickening agent, cooperate with internal water phase thickening agent to further strengthen emulsion stability, utilize the special structure of double emulsion, add vitamin E as internal water phase protective agent in oil phase, solve the problem of easy oxidation and degradation of vitamin C, glycerol in internal water phase, polyglyceryl ricinoleate in oil phase, tween 80 in external water phase synergistically improve the interface strength and structural stability of double emulsion;Preparation of particle size 800nm-1.5 μm can be stored for 6 months, the encapsulation efficiency reaches 90%, and the effective substance only decreases by 30% after 6 months, and the microcapsule prepared by freeze-drying can realize that the effective substance only decreases by 10% after 6 months.
[0007] The purpose of the present application can be realized by the following technical solutions.
[0008] The first aspect of the present application provides a preparation method for preparing submicron double emulsion coated with vitamin c using ultrasonic microreactor high-throughput, the preparation method comprises the following steps:
[0009] (1) preparation of internal water phase solution, oil phase solution and external water phase solution: glycerol, konjac glucomannan and NaCl are added to deionized water, then nitrogen is introduced to remove oxygen under ultrasonic, then vitamin C is added, and stirring is carried out to obtain the internal water phase solution; polyglyceryl ricinoleate, castor oil / IPDI copolymer and vitamin E are added to caprylic acid / capric acid triglyceride, and stirring is carried out to obtain the oil phase solution; tween 80 and phosphate buffer are added to deionized water, and stirring is carried out to obtain the external water phase solution;
[0010] (2) preparation of water-in-oil emulsion: the oil phase solution and the internal water phase solution are mixed according to the oil-water ratio of 3:1, and the coarse emulsion is obtained after homogenization, then the coarse emulsion is injected into the ultrasonic microreactor by using a syringe pump, the droplets are broken by ultrasonic cavitation effect, and the water-in-oil emulsion is obtained;
[0011] (3) preparation of double emulsion: the water-in-oil emulsion and the external water phase solution are synchronously injected into the T-shaped interface of the ultrasonic microreactor by using two syringe pumps, and the submicron double emulsion is prepared by ultrasonic cavitation effect.
[0012] The second aspect of the application provides a preparation method for high-throughput preparation of sub-micron vitamin C-coated microcapsules using an ultrasonic microreactor, comprising the following steps:
[0013] Step S1: preparation of inner aqueous phase solution, oil phase solution and outer aqueous phase solution: glycerol, konjac glucomannan and NaCl are added to deionized water, then nitrogen is introduced to remove oxygen under ultrasonic, then vitamin C is added and stirred to obtain the inner aqueous phase solution; polyglyceryl ricinoleate, castor oil / IPDI copolymer, vitamin E, sucrose and amino acid are added to caprylic / capric triglyceride and stirred to obtain the oil phase solution; Tween 80 and phosphate buffer are added to deionized water and stirred to obtain the outer aqueous phase solution;
[0014] Step S2: preparation of water-in-oil emulsion: the oil phase solution and the inner aqueous phase solution are mixed at an oil-water ratio of 3:1, homogenized to obtain a coarse emulsion, then the coarse emulsion is injected into an ultrasonic microreactor using a syringe pump, and the droplets are broken by ultrasonic cavitation effect to obtain a water-in-oil emulsion;
[0015] Step S3: preparation of double emulsion: the water-in-oil emulsion and the outer aqueous phase solution are synchronously injected into the T-shaped interface of the ultrasonic microreactor through two syringe pumps, and the sub-micron double emulsion is prepared by ultrasonic cavitation effect;
[0016] Step S4: preparation of microcapsules: the sub-micron double emulsion is first subjected to freezing treatment, then subjected to freeze-drying to obtain sub-micron vitamin C-coated microcapsules.
[0017] Preferably, in step (1) and step S1, the glycerol in the inner aqueous phase solution accounts for 0.1-20% of the mass of deionized water, the konjac glucomannan accounts for 0.1-20% of the mass of deionized water, the vitamin C accounts for 0.1-20% of the mass of deionized water, and the NaCl accounts for 0.75% of the mass of deionized water.
[0018] More preferably, in step (1) and step S1, the glycerol in the inner aqueous phase solution accounts for 10% of the mass of deionized water, the konjac glucomannan accounts for 10% of the mass of deionized water, and the vitamin C accounts for 10% of the mass of deionized water.
[0019] Preferably, in step (1), the polyglyceryl ricinoleate in the oil phase solution accounts for 1-10% of the mass of the caprylic acid / capric acid glyceride, vitamin E accounts for 20% of the mass of the caprylic acid / capric acid glyceride, and the castor oil / IPDI copolymer accounts for 0.1-10% of the mass of the caprylic acid / capric acid glyceride; in step S1, the polyglyceryl ricinoleate in the oil phase solution accounts for 1-10% of the mass of the caprylic acid / capric acid glyceride, vitamin E accounts for 20% of the mass of the caprylic acid / capric acid glyceride, the castor oil / IPDI copolymer accounts for 0.1-10% of the mass of the caprylic acid / capric acid glyceride, sucrose accounts for 1% of the mass of the caprylic acid / capric acid glyceride, and the amino acid accounts for 1-3% of the mass of the caprylic acid / capric acid glyceride.
[0020] More preferably, in step (1), the polyglyceryl ricinoleate in the oil phase solution accounts for 5% of the mass of the caprylic acid / capric acid glyceride, and the castor oil / IPDI copolymer accounts for 1% of the mass of the caprylic acid / capric acid glyceride; in step S1, the polyglyceryl ricinoleate in the oil phase solution accounts for 5% of the mass of the caprylic acid / capric acid glyceride, the castor oil / IPDI copolymer accounts for 1% of the mass of the caprylic acid / capric acid glyceride, and the amino acid accounts for 1% of the mass of the caprylic acid / capric acid glyceride.
[0021] More preferably, the amino acid is at least one of glycine and arginine.
[0022] Preferably, in steps (1) and S1, the Tween 80 in the external aqueous phase solution accounts for 1-3% of the mass of the deionized water, and the pH value of the external aqueous phase solution is 3-9.
[0023] More preferably, in steps (1) and S1, the Tween 80 in the external aqueous phase accounts for 1% of the mass of the deionized water.
[0024] Preferably, in steps (3) or S3, the volume ratio of the water-in-oil emulsion to the external aqueous phase solution is 1:9-3:7.
[0025] More preferably, in steps (3) or S3, the volume ratio of the water-in-oil emulsion to the external aqueous phase solution is 1:9.
[0026] Preferably, in steps (2) or S2, the ultrasonic frequency of the ultrasonic microreactor is 18-500 kHz, and the residence time is 0.91-2.27 min.
[0027] More preferably, in steps (2) or S2, the ultrasonic frequency of the ultrasonic microreactor is 18-60 kHz.
[0028] More preferably, in steps (2) or S2, the ultrasonic frequency of the ultrasonic microreactor is 20 kHz.
[0029] Preferably, the hydraulic diameter of the pipe of the ultrasonic microreactor is 0.1-50mm.
[0030] More preferably, the hydraulic diameter of the pipe of the ultrasonic microreactor is 0.5-10mm.
[0031] Preferably, in step (3) or step S3, the ultrasonic power of the ultrasonic microreactor is 30-90W, and the flow rate is 6-15mL / min.
[0032] More preferably, in step (3) or step S3, the ultrasonic power of the ultrasonic microreactor is 90W, and the flow rate is 6.8mL / min.
[0033] The third aspect of the present application provides a sub-micron double emulsion coated with vitamin C prepared by the above preparation method.
[0034] The fourth aspect of the present application provides a sub-micron microcapsule coated with vitamin C prepared by the above preparation method.
[0035] The beneficial effects that can be produced by the present application are as follows:
[0036] (1) The present application first uses an ultrasonic microreactor for the high-efficiency continuous preparation of a double emulsion, thereby solving the problems of wide particle size distribution, high energy consumption, and difficulty in scaling up that exist in traditional emulsion preparation methods. The present application realizes the high-efficiency preparation of a nanoscale W / O / W emulsion by using ultrasonic cavitation effects + microscale mixing through an ultrasonic microreactor, and the particle size can reach 800nm-1.5μm. Continuous flow reaction is realized, which improves production efficiency while ensuring the uniformity of emulsion droplet distribution, and has industrialization potential.
[0037] (2) The present application introduces konjac glucomannan (KGM) as an internal water phase thickening agent, which significantly increases the strong stability of the internal water phase. KGM forms a three-dimensional gel network structure in the internal water phase, increases the viscosity of the internal water phase, and thereby significantly inhibits the migration and release of vitamin C, and improves the encapsulation rate to more than 90%.
[0038] (3) The present application introduces castor oil / IPDI copolymer as an oil phase thickening agent, which significantly enhances the stability of the oil phase. Castor oil / IPDI copolymer forms a three-dimensional gel network structure in the oil phase, increases the viscosity of the oil phase, and further enhances the stability of the emulsion in cooperation with the internal water phase thickening agent.
[0039] (4) The present application uses the special structure of the double emulsion to add vitamin E as an internal water phase protective agent in the oil phase, thereby solving the problem of easy oxidation and degradation of vitamin C.
[0040] (5) Glycerol in the internal water phase, polyglyceryl oleate in the oil phase, and Tween 80 in the external water phase synergistically improve the interfacial strength and structural stability of the double emulsion through the effect of balancing osmotic pressure.
[0041] (6) The double emulsion prepared by the present application has a particle size of 800 nm-1.5 μm, can be stored stably for 6 months, has an encapsulation rate of 90%, and the effective substance is only reduced by 30% after 6 months. The microcapsule prepared by freeze-drying the double emulsion can realize that the effective substance is only reduced by 10% after 6 months. BRIEF DESCRIPTION OF DRAWINGS
[0042] Figure 1 The figure is a comparison chart of emulsion particle sizes of the water-in-oil emulsions in Examples 1-5 stored at room temperature for different days.
[0043] Figure 2 The figure is a comparison chart of optical photographs of the water-in-oil emulsions in Examples 1-5 prepared freshly and stored at room temperature for 28 days.
[0044] Figure 3 The figure is a chart of emulsion particle size distribution changes of the double emulsion in Example 6 after heat treatment at 70°C for different times.
[0045] Figure 4 The figure is a chart of emulsion particle size distribution changes of the double emulsion in Example 7 after heat treatment at 70°C for different times.
[0046] Figure 5 The figure is a chart of emulsion particle size distribution changes of the double emulsion in Example 8 after heat treatment at 70°C for different times.
[0047] Figure 6 The figure is a comparison chart of emulsion particle size changes of the double emulsions in Examples 6-8 after heat treatment at 70°C for different times.
[0048] Figure 7 The figure is an optical photograph of the double emulsion in Examples 6-8 after heat treatment at 70°C for different times.
[0049] Figure 8 The figure is a CLSM photograph of the double emulsion in Examples 6, 9, 10, 11 and Comparative Examples 1-4 obtained by a laser microscope.
[0050] Figure 9 The figure is a comparison chart of encapsulation rates of vitamin C of the double emulsions in Example 6 and Comparative Example 1 stored at 25°C for different times.
[0051] Figure 10 The figure is a scanning electron microscope photograph of the microcapsule in Example 12.
[0052] Figure 11 The figure is a comparison chart of encapsulation rates of vitamin C of the microcapsules in Example 12 and Comparative Example 5 stored at 25°C for different times. DETAILED DESCRIPTION
[0053] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative effort belong to the scope of the present application.
[0054] The experimental methods in the following embodiments are all conventional methods, and the experimental materials used in the following embodiments are all commercially available unless otherwise specified.
[0055] Embodiment 1
[0056] Preparation of water-in-oil emulsion (1% content of polyglycerol ricinoleate):
[0057] (1) Inner aqueous phase solution, oil phase solution: 10% glycerol by mass of deionized water, 10% konjac glucomannan by mass of deionized water, 0.75% NaCl by mass of deionized water were added to deionized water, and then ultrasonic nitrogen was introduced to remove oxygen, and then 10% vitamin C by mass of deionized water was added, and stirring was performed to obtain an inner aqueous phase solution; 1% polyglycerol ricinoleate by mass of caprylic / capric triglyceride, 1% castor oil / IPDI copolymer by mass of caprylic / capric triglyceride, and 20% vitamin E by mass of caprylic / capric triglyceride were added to caprylic / capric triglyceride, and stirring was performed to obtain an oil phase solution; both were stored in a 4°C refrigerator in the dark for standby use;
[0058] (2) Preparation of water-in-oil emulsion: the oil phase solution and the inner aqueous phase solution were mixed at an oil-water ratio of 3:1, a high-speed homogenizer was used at a speed of 7000 rpm for 3 min to prepare a coarse emulsion, and then the coarse emulsion was injected into an ultrasonic microreactor (20 kHz, 120 W) at a flow rate of 6 mL / min (residence time 2.27 min, microreactor dead volume 13.6 mL) using a syringe pump, and the droplets were broken by cavitation effect to obtain a water-in-oil emulsion of 40-800 nm.
[0059] Embodiment 2
[0060] Preparation of water-in-oil emulsion (3% content of polyglycerol ricinoleate):
[0061] Embodiment 2 differs from embodiment 1 in that the polyglycerol ricinoleate is 3% by mass of caprylic / capric triglyceride, and the rest is consistent with embodiment 1.
[0062] Embodiment 3
[0063] Preparation of water-in-oil emulsion (5% content of polyglycerol ricinoleate):
[0064] The difference between Example 3 and Example 1 is that polyglycerol linoleate accounts for 5% of the mass of caprylic / capric triglyceride, while the rest is the same as in Example 1.
[0065] Example 4
[0066] Preparation of water-in-oil emulsion (7% polyglycerol linoleate):
[0067] The difference between Example 4 and Example 1 is that polyglycerol linoleate accounts for 7% of the mass of caprylic / capric triglyceride, while the rest is the same as in Example 1.
[0068] Example 5
[0069] Preparation of water-in-oil emulsion (10% polyglycerol linseed oil):
[0070] The difference between Example 5 and Example 1 is that polyglycerol linoleic acid ester accounts for 10% of the mass of caprylic / capric triglyceride, while the rest is the same as in Example 1.
[0071] The particle size comparison chart of the water-in-oil emulsions in Examples 1-5 after storage at room temperature for different days is shown below. Figure 1 As shown, the optical photographs comparing the freshly prepared water-in-oil emulsions in Examples 1-5 with those stored at room temperature for 28 days are as follows. Figure 2 As shown. By Figure 1 and Figure 2 It can be seen that when the polyglycerol linoleic acid ester accounts for 5% of the mass of caprylic / capric triglyceride in the oil phase solution, the prepared water-in-oil emulsion has the smallest particle size and good stability.
[0072] Example 6
[0073] Preparation of double emulsion (external aqueous phase pH=3, oil-water ratio 1:9):
[0074] (1) Inner aqueous phase solution and oil phase solution: Glycerin (10% by mass of deionized water), konjac glucomannan (10% by mass of deionized water), and NaCl (0.75% by mass of deionized water) were added to deionized water, and nitrogen gas was introduced by ultrasonication to remove oxygen. Then, vitamin C (10% by mass of deionized water) was added and stirred to obtain the inner aqueous phase solution. Polyglycerol linoleic acid ester (5% by mass of caprylic / capric triglyceride), castor oil / IPDI copolymer (1% by mass of caprylic / capric triglyceride), and vitamin E (20% by mass of caprylic / capric triglyceride) were added to caprylic / capric triglyceride and stirred to obtain the oil phase solution. Tween 80 (1% by mass of deionized water) was added to deionized water, and phosphate buffer was added to adjust the pH to 3. The mixture was magnetically stirred at 500 rpm for 30 minutes at 25°C to obtain the outer aqueous phase solution. All solutions were stored in a refrigerator at 4°C in the dark for later use.
[0075] (2) Preparation of water-in-oil emulsion: the oil phase solution and the inner water phase solution were mixed at an oil-water ratio of 3:1, and a coarse emulsion was prepared by homogenizing at a speed of 7000 rpm for 3 min using a high-speed homogenizer. Then, the coarse emulsion was injected into an ultrasonic microreactor (20 kHz, 120 W) at a flow rate of 6 mL / min (residence time 2.27 min, microreactor dead volume 13.6 mL) using a syringe pump, and the droplets were broken by cavitation effect to obtain a water-in-oil emulsion with a particle size of 40-800 nm;
[0076] (3) Preparation of double emulsion: the water-in-oil emulsion and the outer water phase solution were simultaneously injected into the T-shaped interface of the ultrasonic microreactor using two syringe pumps at a volume ratio of 1:9, the inner diameter of the main channel was 4 mm, and the ultrasonic power of the ultrasonic microreactor was controlled at 90 W, and the flow rate was 6.8 mL / min. A submicron double emulsion with a particle size of 800 nm-1.5 μm was prepared by ultrasonic cavitation effect.
[0077] Example 7
[0078] Preparation of double emulsion (pH of outer water phase = 3, oil-water ratio 2:8):
[0079] Example 7 differs from Example 6 in that in step (3), the volume ratio of the water-in-oil emulsion and the outer water phase solution is 2:8, and the rest is consistent with Example 6.
[0080] Example 8
[0081] Preparation of double emulsion (pH of outer water phase = 3, oil-water ratio 3:7):
[0082] Example 8 differs from Example 6 in that in step (3), the volume ratio of the water-in-oil emulsion and the outer water phase solution is 3:7, and the rest is consistent with Example 6.
[0083] The particle size distribution change diagram of the double emulsion obtained in Example 6 after heat treatment at 70°C for different times is shown in Figure 3 , the particle size distribution change diagram of the double emulsion in Example 7 after heat treatment at 70°C for different times is shown in Figure 4 , the particle size distribution change diagram of the double emulsion in Example 8 after heat treatment at 70°C for different times is shown in Figure 5 , and the comparison diagram of the particle size change of the double emulsion in Example 6-Example 8 after heat treatment at 70°C for different times is shown in Figure 6 , and Figures 3-6 It can be seen that when the oil-water ratio of the water-in-oil emulsion and the outer water phase solution in Example 6 is 1:9, the double emulsion obtained has the smallest particle size and has good stability.
[0084] Optical photographs of the double emulsions in Example 6-Example 8 after heat treatment at 70°C for different time are shown in Figure 1. Figure 7 As can be seen from Figure 1, the double emulsions in Example 6-Example 8 all have good stability.
[0085] Example 9
[0086] Preparation of double emulsion (pH of outer aqueous phase = 5, oil / water ratio 1:9):
[0087] The difference between Example 9 and Example 6 is that in step (1), phosphate buffer is added to the outer aqueous phase to adjust the pH value to 5, and the rest is consistent with Example 6.
[0088] Example 10
[0089] Preparation of double emulsion (pH of outer aqueous phase = 7, oil / water ratio 1:9):
[0090] The difference between Example 10 and Example 6 is that in step (1), phosphate buffer is added to the outer aqueous phase to adjust the pH value to 7, and the rest is consistent with Example 6.
[0091] Example 11
[0092] Preparation of double emulsion (pH of outer aqueous phase = 9, oil / water ratio 1:9):
[0093] The difference between Example 11 and Example 6 is that in step (1), phosphate buffer is added to the outer aqueous phase to adjust the pH value to 9, and the rest is consistent with Example 6.
[0094] Comparative Example 1
[0095] Preparation of double emulsion:
[0096] The difference between Comparative Example 1 and Example 6 is that the inner aqueous phase does not contain konjac glucomannan, and the rest is consistent with Example 6.
[0097] Comparative Example 2
[0098] Preparation of double emulsion:
[0099] The difference between Comparative Example 2 and Example 9 is that the inner aqueous phase does not contain konjac glucomannan, and the rest is consistent with Example 9.
[0100] Comparative Example 3
[0101] Preparation of double emulsion:
[0102] The difference between Comparative Example 3 and Example 10 is that the inner aqueous phase does not contain konjac glucomannan, and the rest is consistent with Example 10.
[0103] Comparative Example 4
[0104] Preparation of the double emulsion:
[0105] Comparative Example 4 differs from Example 11 in that the konjac glucomannan is not contained in the internal aqueous phase, and the rest is consistent with Example 11.
[0106] The CLSM photos of the double emulsions in Examples 6, 9, 10, 11 and Comparative Examples 1-4 obtained by laser microscope are shown in FIG. 1, and the particle size distribution is shown in FIG. 2. Figure 8 As can be seen, without adding the thickening agent konjac glucomannan (KGM) in the internal aqueous phase in Comparative Examples 1-4, the particle size of the double emulsions is larger as a whole than that of Examples 6, 9, 10, 11, and the particle size increases with the increase of pH value. Figure 8
[0107] The encapsulation efficiency of vitamin C was determined by the following method:
[0108] The encapsulation efficiency of vitamin C was determined by high performance liquid chromatography. In the experiment, the double emulsion was sampled in an appropriate amount and diluted 15 times by isopropionic acid to break the emulsion, so as to release the vitamin C in the internal aqueous phase and free in the external aqueous phase, and obtain the total amount of vitamin C in the system. The ultrafiltration centrifuge tube with a flow rate of 100 kDa was centrifuged at 3000 rpm and 4°C for 10 min, and the free vitamin C was obtained from the supernatant. Then the total vitamin C content and the free vitamin C content in the external aqueous phase were determined by HPLC. A 100 mm long reversed-phase C18 chromatographic column was used, the mobile phase A was composed of 95% chromatographic grade water, 0.05 mol / L potassium dihydrogen phosphate solution (pH adjusted to 2.5 by hydrochloric acid) and 5% chromatographic grade formic acid, and the potassium dihydrogen phosphate solution was filtered in advance by using a microporous filter to remove solid impurities. The single injection was 10 μL, the detection wavelength was set to 244 nm, the flow rate was 0.4 mL / min, and the column temperature was controlled at 30°C. The encapsulation efficiency of vitamin C was calculated according to the following formula:
[0109]
[0110] In the formula, C is the encapsulation efficiency of vitamin C (%), Wtotal is the total concentration of vitamin C in the system (μg / mL), and Wfree is the free concentration of vitamin C in the external aqueous phase (μg / mL).
[0111] The encapsulation efficiency of vitamin C of the double emulsion in Example 6 and Comparative Example 1 stored at 25°C for different time was shown in FIG. 3, and the encapsulation efficiency of vitamin C of the double emulsion in Example 11 stored at 25°C for different time was shown in FIG. 4. Figure 9 As can be seen, after adding the thickening agent konjac glucomannan (KGM) in the internal aqueous phase in Example 6, the encapsulation efficiency decreases less with time, and the stability is better.
[0112] Example 12
[0113] Preparation of the double emulsion:
[0114] Step S1: inner aqueous phase solution, oil phase solution: glycerol accounting for 10% of the mass of deionized water, konjac glucomannan accounting for 10% of the mass of deionized water, NaCl accounting for 0.75% of the mass of deionized water were added to deionized water, and then oxygen was removed by ultrasonic nitrogen, then vitamin C accounting for 10% of the mass of deionized water was added, and stirring was performed to obtain an inner aqueous phase solution; polyglyceryl ricinoleate accounting for 5% of the mass of caprylic acid / capric acid triglyceride, castor oil / IPDI copolymer accounting for 1% of the mass of caprylic acid / capric acid triglyceride, vitamin E accounting for 20% of the mass of caprylic acid / capric acid triglyceride, sucrose accounting for 1% of the mass of caprylic acid / capric acid triglyceride, and glycine accounting for 1% of the mass of caprylic acid / capric acid triglyceride were added to caprylic acid / capric acid triglyceride, and stirring was performed to obtain an oil phase solution; Tween 80 accounting for 1% of the mass of deionized water was added to deionized water, and magnetic stirring was performed at a temperature of 25℃ and a speed of 500 rpm for 30 minutes to obtain an outer aqueous phase solution; all were stored in a 4℃ refrigerator in the dark;
[0115] Step S2: preparation of a water-in-oil emulsion: the oil phase solution and the inner aqueous phase solution were mixed at an oil-water ratio of 3:1, a high-speed homogenizer was used at a speed of 7000 rpm for 3 minutes to obtain a coarse emulsion, and then the coarse emulsion was injected into an ultrasonic microreactor (20 kHz, 120 W) at a flow rate of 6 mL / min (residence time 2.27 min, microreactor dead volume 13.6 mL) using a syringe pump, and the droplets were broken by cavitation effect to obtain a water-in-oil emulsion with a particle size of 40-800 nm;
[0116] Step S3: preparation of a double emulsion: the water-in-oil emulsion and the outer aqueous phase solution were synchronously injected into the T-shaped interface of the ultrasonic microreactor using two syringe pumps at a volume ratio of 1:9, the inner diameter of the main channel was 4 mm, the ultrasonic power of the ultrasonic microreactor was controlled at 90 W, and the flow rate was 6.8 mL / min, and a submicron double emulsion with a particle size of 800 nm-1.5 μm was prepared by ultrasonic cavitation effect;
[0117] Step S4: preparation of microcapsules: the submicron double emulsion was frozen in a-20℃ refrigerator for 12 hours, and then freeze-dried in a freeze dryer to obtain submicron microcapsules coated with vitamin C.
[0118] The scanning electron microscope image of the microcapsules in this example is shown in Figure 10 As can be seen, the microcapsules have a submicron particle size.
[0119] Comparative Example 5
[0120] Preparation of microcapsules:
[0121] Comparative Example 5 and Example 12 differ in that the double emulsion in Comparative Example 1 was frozen in a -20°C refrigerator for 12 h and then freeze-dried in a freeze dryer to obtain sub-micron microcapsules coated with vitamin C.
[0122] The encapsulation efficiency of vitamin C of the microcapsules in Example 12 and Comparative Example 5 obtained by the test was measured at 25°C after storage for different time periods as shown in Table 2. Figure 11 As shown in Table 2, it can be seen that the encapsulation efficiency of Example 12 decreases less with time after the thickening agent konjac glucomannan (KGM) is added to the inner water phase, and the stability is better.
[0123] The above describes a preferred embodiment of the present application, but the present application is not limited to the described embodiment, and those skilled in the art can make various equivalent modifications or replacements without departing from the spirit of the present application, and these equivalent modifications or replacements are all included in the scope defined by the claims of the present application.
Claims
1. A method for high-throughput preparation of vitamin C-coated sub-micron double emulsions using an ultrasonic microreactor, characterized in that, The preparation method comprises the following steps: (1) Preparation of inner water phase solution, oil phase solution and outer water phase solution: glycerol, konjac glucomannan and NaCl are added to deionized water, then nitrogen is introduced to remove oxygen by ultrasonic, then vitamin C is added, and stirring is performed to obtain the inner water phase solution; polyglyceryl ricinoleate, castor oil / IPDI copolymer and vitamin E are added to caprylic acid / capric acid triglyceride, and stirring is performed to obtain the oil phase solution; Tween 80 and phosphate buffer are added to deionized water, and stirring is performed to obtain the outer water phase solution; (2) Preparation of water-in-oil emulsion: the oil phase solution and the inner water phase solution are mixed at an oil-water ratio of 3:1, and a coarse emulsion is obtained after homogenization, then the coarse emulsion is injected into an ultrasonic microreactor by using a syringe pump, and the droplets are broken by ultrasonic cavitation effect to obtain the water-in-oil emulsion; (3) Preparation of double emulsion: the water-in-oil emulsion and the outer water phase solution are synchronously injected into a T-shaped interface of the ultrasonic microreactor by using two syringe pumps, and the submicron double emulsion is prepared by ultrasonic cavitation effect.
2. A method for high-throughput preparation of sub-micron microcapsules coated with vitamin C using an ultrasonic microreactor, characterized by, The preparation method comprises the following steps: Step S1: Preparation of inner water phase solution, oil phase solution and outer water phase solution: glycerol, konjac glucomannan and NaCl are added to deionized water, then nitrogen is introduced to remove oxygen by ultrasonic, then vitamin C is added, and stirring is performed to obtain the inner water phase solution; polyglyceryl ricinoleate, castor oil / IPDI copolymer, vitamin E, sucrose and amino acid are added to caprylic acid / capric acid triglyceride, and stirring is performed to obtain the oil phase solution; Tween 80 and phosphate buffer are added to deionized water, and stirring is performed to obtain the outer water phase solution; Step S2: Preparation of water-in-oil emulsion: the oil phase solution and the inner water phase solution are mixed at an oil-water ratio of 3:1, and a coarse emulsion is obtained after homogenization, then the coarse emulsion is injected into an ultrasonic microreactor by using a syringe pump, and the droplets are broken by ultrasonic cavitation effect to obtain the water-in-oil emulsion; Step S3: Preparation of double emulsion: the water-in-oil emulsion and the outer water phase solution are synchronously injected into a T-shaped interface of the ultrasonic microreactor by using two syringe pumps, and the submicron double emulsion is prepared by ultrasonic cavitation effect. Step S4: Preparation of microcapsules: the submicron double emulsion is first subjected to freezing treatment, and then is subjected to freeze-drying to obtain the submicron microcapsules coated with vitamin C.
3. The method according to claim 1 or 2, wherein the method is characterized in that, In step (1) and step S1, the glycerol accounts for 0.1-20% of the mass of the deionized water, the konjac glucomannan accounts for 0.1-20% of the mass of the deionized water, the vitamin C accounts for 0.1-20% of the mass of the deionized water, and the NaCl accounts for 0.75% of the mass of the deionized water.
4. The method according to claim 1 or 2, wherein the method is characterized in that, In step (1), the polyglyceryl ricinoleate in the oil phase solution accounts for 1-10% of the mass of the caprylic acid / capric acid glyceride, vitamin E accounts for 20% of the mass of the caprylic acid / capric acid glyceride, and the castor oil / IPDI copolymer accounts for 0.1-10% of the mass of the caprylic acid / capric acid glyceride; in step S1, the polyglyceryl ricinoleate in the oil phase solution accounts for 1-10% of the mass of the caprylic acid / capric acid glyceride, vitamin E accounts for 20% of the mass of the caprylic acid / capric acid glyceride, the castor oil / IPDI copolymer accounts for 0.1-10% of the mass of the caprylic acid / capric acid glyceride, sucrose accounts for 1% of the mass of the caprylic acid / capric acid glyceride, and the amino acid accounts for 1-3% of the mass of the caprylic acid / capric acid glyceride.
5. The method according to claim 1 or 2, wherein the method is characterized in that, In step (1) and step S1, the Tween 80 in the external aqueous phase solution accounts for 1-3% of the mass of the deionized water, and the pH value of the external aqueous phase solution is 3-9.
6. The method according to claim 1 or 2, wherein the method is a method for high-throughput preparation of sub-micron double emulsion or microcapsule coated with vitamin C using an ultrasonic microreactor. In step (3) or step S3, the volume ratio of the water-in-oil emulsion and the external aqueous phase solution is 1:9-3:
7.
7. The method according to claim 1 or 2, wherein the method is a method for high-throughput preparation of sub-micron double emulsion or microcapsule coated with vitamin C using an ultrasonic microreactor. In step (2) or step S2, the ultrasonic frequency of the ultrasonic microreactor is 18-500 kHz, and the residence time is 0.91-2.27 min.
8. The method according to claim 1 or 2, wherein the method is a method for high-throughput preparation of sub-micron double emulsion or microcapsule coated with vitamin C using an ultrasonic microreactor. In step (3) or step S3, the ultrasonic power of the ultrasonic microreactor is 30-90 W, and the flow rate is 6-15 mL / min.
9. A sub-micron double emulsion coated with vitamin C prepared by the preparation method of claim 1.
10. A sub-micron microcapsule coated with vitamin C prepared by the preparation method of claim 2.