High-stability coenzyme Q10 and vitamin C composite emulsion as well as preparation method and device thereof

Abstract

The invention discloses a high-stability coenzyme Q10 and vitamin C composite emulsion as well as a preparation method and device thereof, and particularly relates to the technical field of vitamin composite emulsions.The high-stability coenzyme Q10 and vitamin C composite emulsion is prepared from the following components in percentage by weight: 0.5-2% of coenzyme Q10; 1-3% of vitamin C; the emulsion comprises the following components in percentage by weight: 20-30% of an emulsifier, 3-8% of a double embedding carrier, 2-5% of a compound emulsifier, the balance of deionized water, polyethylene glycol-vitamin E palmitate which accounts for 0.2-0.5% of the total weight of the emulsion, and EDTA disodium which accounts for 0.05-0.1% of the total weight of the emulsion. By adopting the composite emulsifier with a specific structure and the dual embedding carrier with clear function orientation, a composite film with higher strength and better toughness can be formed on an oil-water interface, Ostwald ripening and coalescence of emulsion droplets are greatly inhibited, the most suitable microenvironments are respectively provided for two active ingredients with different properties, and the preparation method has the advantages of simple operation, low cost and high efficiency. Therefore, the technical bottleneck that the two components are difficult to stably coexist for a long time in a water phase system is synergistically overcome, and meanwhile, each batch of products can reach a highly-uniform nanoscale dispersed state, and the particle size distribution is extremely narrow.

Description

Technical Field

[0001] This invention relates to the field of vitamin complex emulsion technology, and more specifically, to a highly stable coenzyme Q10 and vitamin C complex emulsion, as well as its preparation method and apparatus. Background Technology

[0002] In the research and development and production of coenzyme Q10 and vitamin C compound emulsions, the synergistic effect of the two on antioxidant, skin care and health care effects has been widely recognized, and has become a popular research and development direction in the cosmetics, food and health products industries.

[0003] On the one hand, coenzyme Q10 is highly hydrophobic, while vitamin C is easily oxidized. The two active ingredients have very different properties. The oil-water interface film formed by the linear emulsifier used in traditional technology has low strength and poor toughness, making it difficult to inhibit the Ostwald ripening and aggregation of emulsion droplets. Moreover, the single encapsulation technology cannot provide suitable microenvironments for the two separately, which leads to problems such as inactivation and separation of the two components in the aqueous system, making it difficult to achieve long-term stable coexistence. On the other hand, existing composite emulsion preparation processes rely heavily on experience, lacking real-time monitoring and precise control of the emulsification process. They cannot dynamically adjust key parameters such as stirring speed, making it difficult to control the emulsion particle size within the optimal range. This results in a wide particle size distribution and significant batch-to-batch product quality differences and poor consistency, hindering the upgrade from experience-based production to precision manufacturing and severely impacting product reliability and market acceptance. Summary of the Invention

[0004] In order to overcome the above-mentioned defects of the prior art, the present invention provides a highly stable coenzyme Q10 and vitamin C complex emulsion, and a method and apparatus for preparing the same, so as to solve the problems mentioned in the background art.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a highly stable coenzyme Q10 and vitamin C complex emulsion, composed of the following components by weight percentage: 0.5-2% Coenzyme Q10; 1-3% Vitamin C; 2-5% of a composite emulsifier, wherein the composite emulsifier is composed of branched polyether-modified siloxane and soap bark extract in a mass ratio of 3:1 to 2:1, wherein the branched polyether-modified siloxane has a molecular weight of 5000-15000 Da and a degree of branching of 10-30%; 3-8% of a dual-encapsulation carrier, wherein the dual-encapsulation carrier is a mixture of polylactic acid-glycolic acid copolymer and β-cyclodextrin; The remaining deionized water; The polylactic acid-glycolic acid copolymer is used to encapsulate the coenzyme Q10, and the β-cyclodextrin is used to encapsulate the vitamin C.

[0006] Preferably, the mass ratio of polylactic acid-hydroxyacetic acid copolymer to β-cyclodextrin in the double-encapsulated carrier is 1:1 to 1:5.

[0007] Preferably, it further comprises 0.2-0.5% polyethylene glycol-vitamin E palmitate by weight of the total emulsion, and 0.05-0.1% disodium EDTA by weight of the total emulsion; The amount of deionized water used is reduced accordingly to make up the surplus.

[0008] Preferably, the emulsion is measured by dynamic light scattering method, and its volume average particle size Z-Average is 50nm to 200nm, and its polydispersity index PDI is not greater than 0.15. The emulsion is measured by laser Doppler electrophoresis method, and its Zeta potential is not higher than -30mV or not lower than +30mV.

[0009] A method for preparing the highly stable coenzyme Q10 and vitamin C complex emulsion as described above is also provided, comprising the following steps: S1: Pre-encapsulation treatment, wherein the coenzyme Q10 and the polylactic acid-glycolic acid copolymer are ultrasonically dispersed in an oil phase carrier to form oil phase encapsulated particles; the vitamin C and the β-cyclodextrin are stirred and mixed in an aqueous phase at 35-40°C to encapsulate the particles, forming an aqueous phase encapsulation solution; S2: Pre-emulsification: The composite emulsifier is dissolved in a portion of deionized water to obtain an emulsifier aqueous solution, which is then mixed and stirred with the aqueous embedding solution at 40-45°C to perform pre-emulsification and obtain an aqueous matrix. S3: Stepwise emulsification, the oil phase embedded particles are added to the aqueous phase matrix, and stirred and mixed at 300-500 rpm at 40-45℃ for 10-20 minutes to form a primary emulsion; S4: Dynamic equilibrium, the primary emulsion is subjected to dynamic equilibrium treatment at 35-40℃ under continuous stirring, and the volume average particle size of the emulsion is controlled to be ≤200nm by online particle size monitoring; S5: Homogenization and post-treatment: The emulsion after dynamic equilibrium treatment is subjected to high-pressure homogenization at 80-100MPa, then cooled to below 25℃, and polyethylene glycol-vitamin E palmitate and disodium EDTA are added and mixed evenly to obtain the composite emulsion.

[0010] Preferably, the ultrasonic dispersion frequency in S1 is 40 kHz, and the processing time is 3 to 8 minutes; The mixing and inclusion process is carried out at 35°C to 40°C for 15 to 25 minutes.

[0011] Preferably, in the dynamic balancing process of S4: The particle size of the emulsion is monitored online in real time, and the stirring speed is dynamically adjusted based on the monitored particle size data to ensure that the volume average particle size of the emulsion reaches and is maintained below 200 nm.

[0012] An apparatus for carrying out the preparation method as described above is also provided, comprising: connected sequentially via conduits: A pre-emulsification tank, wherein a first stirrer is provided inside the pre-emulsification tank and a first heating jacket is fixedly sleeved on the outside of the pre-emulsification tank; A dynamic balancing tank, wherein a second stirrer is provided inside the dynamic balancing tank, a second heating jacket is fixedly sleeved on the outside of the dynamic balancing tank, and an online particle size monitor for real-time monitoring of the particle size of the emulsion inside the tank is fixedly installed on the top of the inner wall of the dynamic balancing tank. High-pressure homogenizer; And a controller electrically connected to the online particle size monitor and the second agitator respectively, the controller being fixedly mounted on the top of the dynamic balance tank.

[0013] Preferably, the second agitator is a double-layer agitator, with an upper layer being an oblique blade agitator and a lower layer being a turbine agitator.

[0014] Preferably, the controller is configured to automatically adjust the rotation speed of the second stirrer based on the real-time particle size data fed back by the online particle size monitor, so as to control the volume average particle size of the emulsion in the dynamic equilibrium tank within a predetermined range.

[0015] The technical effects and advantages of this invention are as follows: By employing a composite emulsifier with a specific structure and a dual encapsulation carrier with a clear functional orientation, the combination of branched polyether-modified siloxane and natural soap bark extract can form a composite film with higher strength and better toughness at the oil-water interface compared to traditional linear emulsifiers. This greatly inhibits the Ostwald ripening and aggregation of emulsion droplets. Addressing the inherent contradiction between the strong hydrophobicity of coenzyme Q10 and the easy oxidation of vitamin C, PLGA is used to encapsulate coenzyme Q10 at the nanoscale, while β-cyclodextrin is used to encapsulate vitamin C at the molecular level. The dual encapsulation technology produces a significant synergistic effect, providing the most suitable microenvironment for the two active ingredients with different properties, thereby synergistically overcoming the industry technical bottleneck that makes it difficult for the two to coexist stably in an aqueous system for a long time. The emulsification process is monitored in real time by an online particle size monitor, and the data is fed back to the control system to dynamically adjust key parameters such as stirring speed. This ensures that the emulsion particle size is always precisely controlled within the optimal nanometer range, creating a precise and controllable process from pre-embedding, stepwise emulsification to dynamic equilibrium. This closed-loop control process based on real-time feedback ensures that each batch of products achieves a highly uniform nanoscale dispersion state with an extremely narrow particle size distribution. This realizes a manufacturing upgrade from experience-driven to data-driven, significantly improving the batch consistency and quality reliability of the products. By deeply integrating the formulation, process, and equipment, and through the dynamic balance tank that integrates online monitoring and feedback control functions, the device provides a physical carrier for the above-mentioned processes, enabling intelligent control. This special device, tailored for specific processes, is closely combined with unique formulations and innovative processes. It not only avoids the use of toxic and harmful solvents, conforming to the trend of green production, but also, due to its high integration and specificity, is easy to achieve large-scale and stable production. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the method flow of the present invention.

[0017] Figure 2 This is a schematic diagram of the preparation apparatus of the present invention.

[0018] The attached figures are labeled as follows: 1. Pre-emulsification tank; 11. First agitator; 12. First heating jacket; 2. Dynamic balancing tank; 21. Second agitator; 22. Second heating jacket; 23. Online particle size monitor; 211. Inclined blade propeller; 212. Turbine propeller; 3. High-pressure homogenizer; 4. Controller. Detailed Implementation

[0019] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] Example 1: Preparation of a highly stable coenzyme Q10 and vitamin C complex emulsion 1. Formula This embodiment provides a specific composite emulsion formulation, the components and their weight percentages of which are as follows: Coenzyme Q10: 1.0% Vitamin C: 2.0% Compound emulsifier: 3.0% Among them, the branched polyether-modified siloxane has a molecular weight of approximately 10,000 Da and a branching degree of approximately 20% (2.0%). Soapberry bark extract: 1.0% Double-encapsulated carrier: 6.0% Among them, polylactic acid-glycolic acid copolymer PLGA, Mw 15000 Da, LA:GA = 75:25:2.0% β-Cyclodextrin: 4.0%, meaning the mass ratio of PLGA to β-cyclodextrin is 1:2. Polyethylene glycol-vitamin E palmitate, PPG-10: 0.3% Disodium EDTA: 0.08% Deionized water: Add to 100.0% 2. Preparation method The specific steps are as follows: S1 pre-embedding treatment: Preparation of oil-phase embedded particles: Weigh the prescribed amount of coenzyme Q10, add it to 10g of caprylic / capric triglyceride, stir and dissolve it in a 60℃ water bath, add the prescribed amount of PLGA, and use an ultrasonic cell disruptor to ultrasonically disperse at a frequency of 40kHz for 5 minutes to obtain a uniform, semi-transparent oil-phase embedded particle dispersion.

[0021] Preparation of aqueous embedding solution: Dissolve the prescribed amount of vitamin C in an appropriate amount of phosphate buffer solution with a pH of 5.5. Add the prescribed amount of β-cyclodextrin, place in a constant temperature water bath at 35°C, and stir at 200 rpm for 20 minutes to carry out the inclusion reaction, obtaining a clear aqueous embedding solution.

[0022] S2 pre-emulsification: The formulated amounts of the branched polyether-modified siloxane and soap bark extract were added to the remaining deionized water and stirred at 45°C and 300 rpm until completely dissolved to obtain an aqueous emulsifier solution. At the same temperature, the above aqueous encapsulation solution was slowly added to the aqueous emulsifier solution, and stirred at 300 rpm for 10 minutes to obtain a homogeneous aqueous matrix.

[0023] S3 stepwise emulsification: The prepared oil-phase embedded particle dispersion was slowly added dropwise to the aqueous matrix under constant temperature of 45℃ and stirring at 400 rpm. After the addition was complete, the reaction was continued for 15 minutes at the same temperature and stirring speed to form a milky white primary emulsion.

[0024] S4 Dynamic Balance: Transfer the colostrum to a suitable location. Figure 1In the dynamic equilibrium tank 2 of the dedicated preparation apparatus shown, the second heating jacket 22 is turned on to maintain the temperature inside the tank at 38°C. The second stirrer 21 is started and runs at a speed of 350 rpm. At the same time, the online particle size monitor 23 is turned on to monitor the particle size of the emulsion in the tank in real time. The controller 4 receives the particle size data and executes the preset PID control algorithm: when the real-time volume average particle size is higher than 180 nm, the stirring speed is automatically increased to a maximum of 500 rpm; when the particle size is lower than 150 nm, the speed is automatically reduced to a minimum of 250 rpm. This dynamic equilibrium process continues until the online monitoring shows that the volume average particle size of the emulsion is stable within the range of 165±5 nm for more than 5 minutes, indicating that the system has reached a dynamic equilibrium state.

[0025] S5 Homogenization and Post-processing: The balanced emulsion was transferred to a high-pressure homogenizer 3 and homogenized three times at a pressure of 90 MPa. The homogenized emulsion was then rapidly cooled to below 25°C using a cooler. Subsequently, the formulated amounts of polyethylene glycol-vitamin E palmitate and disodium EDTA were added and mixed thoroughly by low-speed stirring to obtain the final highly stable coenzyme Q10 and vitamin C complex emulsion.

[0026] 3. Product performance testing and results To verify the effectiveness of the present invention, the emulsion obtained in Example 1 was tested and compared with the comparative example.

[0027] Test method: Particle size and Zeta potential: The volume average particle size (Z-Average), polydispersity index (PDI), and Zeta potential of the emulsion were measured using a Malvern NanoZS90 laser particle size analyzer at 25°C.

[0028] Accelerated stability test: The sample was sealed in a transparent glass bottle and placed in a constant temperature incubator at 60±1℃. Samples were taken on day 0, day 15 and day 30.

[0029] Determination of active ingredient retention: The contents of coenzyme Q10 and vitamin C in the sample were determined by high performance liquid chromatography (HPLC). Chromatographic conditions: C18 column, mobile phase: methanol:water = 80:20, detection wavelength: 285nm Q10 and 245nm VC. Retention rate (%) = (Ct / C0) × 100%, where Ct is the content at time t and C0 is the initial content.

[0030] Physical stability observation: Visually and microscopically observe whether the sample exhibits stratification, precipitation, flocculation, or other phenomena after the accelerated test.

[0031] Comparative Example 1: Except for replacing the composite emulsifier with an equal amount of polysorbate 80 and Tween 80, the formulation and preparation process were the same as in Example 1.

[0032] Comparative Example 2: Except for not adding a double encapsulation carrier, i.e. not performing a pre-encapsulation step, Q10 is directly dissolved in the oil phase and VC is directly dissolved in the aqueous phase, the formulation and preparation process are the same as in Example 1.

[0033] Comparative Example 3: The dynamic equilibrium S4 was omitted in the preparation process. After the primary emulsion S3 was completed, high-pressure homogenization S5 was carried out directly. The rest was the same as in Example 1.

[0034] The test results are shown in the table below: The composite emulsion provided in Example 1 of this invention is as follows: It exhibits excellent initial dispersibility: small particle size of 165nm and extremely narrow distribution PDI=0.10, and high Zeta potential of -38.5mV, indicating that it has strong electrostatic repulsion to maintain long-term physical stability.

[0035] It exhibits excellent chemical stability: after being stored at a harsh temperature of 60°C for 30 days, the retention rate of both core active ingredients exceeded 90%, which is significantly higher than that of each pair. This directly confirms the unexpected technical effect brought about by the synergy of the specific composite emulsifier, the dual encapsulation carrier, and the dynamic equilibrium process.

[0036] Excellent physical stability: No stratification or precipitation was observed after accelerated testing, indicating that the emulsion system of this invention is highly stable.

[0037] One specific embodiment of the preparation apparatus used in this invention is as follows: Figure 2 As shown.

[0038] The pre-emulsification tank 1 has a volume of 50L and is made of 316L stainless steel. Its first agitator 11 is an anchor-type agitator, and the temperature control accuracy of the first heating jacket 12 is ±0.5℃. The dynamic balance tank 2 has a volume of 30L. The upper inclined blade 211 of its second agitator 21 is mainly used to generate axial flow, and the lower turbine blade 212 is mainly used to generate radial shear. The two work together to form a complex flow field in the tank, which is conducive to the homogenization and dynamic balance of particles. The online particle size monitor 23 is an insertion laser probe with a measurement frequency of 1 time / 10 seconds.

[0039] High-pressure homogenizer 3 is a horizontal plunger homogenizer with a working pressure range of 50-150MPa.

[0040] The controller 4 is an industrial PLC equipped with a touch screen human-machine interface. Its internal preset control program can adjust the speed of the second stirrer 21 within the range of 200-600 rpm by adjusting the output of the frequency converter based on the feedback signal of the online particle size monitor 23, forming a closed-loop control to ensure the controllability and reproducibility of the dynamic balance process.

[0041] The various devices are connected via sanitary piping and pumps.

[0042] In summary, this invention, through a specific formulation system, innovative preparation process, and dedicated intelligent device, successfully solves the problem of poor stability in the coenzyme Q10 and vitamin C compound system. The resulting product has achieved significantly better results than existing technologies in terms of particle size and storage stability.

[0043] Finally, the following points should be noted: First, in the description of this application, it should be noted that, unless otherwise specified and limited, the terms "installation", "connection", and "linkage" should be interpreted broadly, and can be mechanical or electrical connections, or internal connections between two components, or direct connections. "Up", "down", "left", "right", etc. are only used to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may change. Secondly: The accompanying drawings of the embodiments disclosed in this invention only involve the structures involved in the embodiments disclosed in this invention. Other structures can refer to the general design. In the absence of conflict, the same embodiment and different embodiments of this invention can be combined with each other. In conclusion, the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. The high-stability coenzyme Q10 and vitamin C compound emulsion is characterized by: It consists of the following components by weight percentage: 0.5-2% Coenzyme Q10; 1-3% Vitamin C; 2-5% of a composite emulsifier, wherein the composite emulsifier is composed of branched polyether-modified siloxane and soap bark extract in a mass ratio of 3:1 to 2:1, wherein the branched polyether-modified siloxane has a molecular weight of 5000-15000 Da and a degree of branching of 10-30%; 3-8% of a dual-encapsulation carrier, wherein the dual-encapsulation carrier is a mixture of polylactic acid-glycolic acid copolymer and β-cyclodextrin; The remaining deionized water; The polylactic acid-glycolic acid copolymer is used to encapsulate the coenzyme Q10, and the β-cyclodextrin is used to encapsulate the vitamin C.

2. The highly stable coenzyme Q10 and vitamin C compound emulsion according to claim 1, characterized in that: The mass ratio of polylactic acid-hydroxyacetic acid copolymer to β-cyclodextrin in the double-encapsulated carrier is 1:1 to 1:

5.

3. The highly stable coenzyme Q10 and vitamin C compound emulsion according to claim 1, characterized in that: It also contains 0.2-0.5% polyethylene glycol-vitamin E palmitate by weight of the emulsion, and 0.05-0.1% disodium EDTA by weight of the emulsion. The amount of deionized water used is reduced accordingly to make up the surplus.

4. The highly stable coenzyme Q10 and vitamin C compound emulsion according to claim 1, characterized in that: The emulsion was measured by dynamic light scattering method, and its volume average particle size was 50 nm to 200 nm, and its polydispersity index was not greater than 0.

15. The emulsion was measured by laser Doppler electrophoresis method, and its Zeta potential was not higher than -30 mV or not lower than +30 mV.

5. A method for preparing a highly stable coenzyme Q10 and vitamin C complex emulsion as described in any one of claims 1-4, characterized in that: Includes the following steps: S1: Pre-encapsulation treatment, wherein the coenzyme Q10 and the polylactic acid-glycolic acid copolymer are ultrasonically dispersed in an oil phase carrier to form oil phase encapsulated particles; the vitamin C and the β-cyclodextrin are stirred and mixed in an aqueous phase at 35-40°C to encapsulate the particles, forming an aqueous phase encapsulation solution; S2: Pre-emulsification: The composite emulsifier is dissolved in a portion of deionized water to obtain an emulsifier aqueous solution, which is then mixed and stirred with the aqueous embedding solution at 40-45°C to perform pre-emulsification and obtain an aqueous matrix. S3: Stepwise emulsification, the oil phase embedded particles are added to the aqueous phase matrix, and stirred and mixed at 300-500 rpm at 40-45℃ for 10-20 minutes to form a primary emulsion; S4: Dynamic equilibrium, the primary emulsion is subjected to dynamic equilibrium treatment at 35-40℃ under continuous stirring, and the volume average particle size of the emulsion is controlled to be ≤200nm by online particle size monitoring; S5: Homogenization and post-treatment: The emulsion after dynamic equilibrium treatment is subjected to high-pressure homogenization at 80-100MPa, then cooled to below 25℃, and polyethylene glycol-vitamin E palmitate and disodium EDTA are added and mixed evenly to obtain the composite emulsion.

6. The method for preparing the highly stable coenzyme Q10 and vitamin C complex emulsion according to claim 5, characterized in that: The ultrasonic dispersion frequency in S1 is 40kHz, and the processing time is 3 to 8 minutes. The mixing and inclusion process is carried out at 35°C to 40°C for 15 to 25 minutes.

7. The method for preparing the highly stable coenzyme Q10 and vitamin C complex emulsion according to claim 5, characterized in that: During the dynamic balancing process in S4: The particle size of the emulsion is monitored online in real time, and the stirring speed is dynamically adjusted based on the monitored particle size data to ensure that the volume average particle size of the emulsion reaches and is maintained below 200 nm.

8. An apparatus for carrying out the method according to any one of claims 5-7, characterized in that: Including those connected sequentially via pipes: A pre-emulsification tank (1) is provided inside the pre-emulsification tank (1), and a first heating jacket (12) is fixedly sleeved on the outside of the pre-emulsification tank (1). A dynamic balance tank (2) is provided inside the dynamic balance tank (2), and a second stirrer (21) is provided on the outside of the dynamic balance tank (2). A second heating jacket (22) is fixedly installed on the top of the inner wall of the dynamic balance tank (2) for real-time monitoring of the particle size of the emulsion in the tank. High-pressure homogenizer (3); And a controller (4) electrically connected to the online particle size monitor (23) and the second stirrer (21), respectively, the controller (4) being fixedly mounted on top of the dynamic balance tank (2).

9. The apparatus for preparing a highly stable coenzyme Q10 and vitamin C complex emulsion according to claim 8, characterized in that: The second agitator (21) is a double-layer agitator, with an upper layer of oblique blade (211) and a lower layer of turbine blade (212).

10. The apparatus for preparing a highly stable coenzyme Q10 and vitamin C complex emulsion according to claim 8, characterized in that: The controller (4) is configured to automatically adjust the rotation speed of the second stirrer (21) based on the real-time particle size data fed back by the online particle size monitor (23) so as to control the volume average particle size of the emulsion in the dynamic balance tank (2) within a predetermined range.

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