Liquid preparation containing vitamin A and preparation method thereof
By designing an oil-water two-phase system and using high-pressure homogenization technology, the stability problem of vitamin A liquid formulations has been solved, achieving high encapsulation efficiency and long-term stability, making them suitable for functional foods and health products.
Patent Information
- Application Number
- CN202511883847.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-15
- Publication Date
- 2026-01-23
AI Technical Summary
Vitamin A has poor stability in liquid formulations and is easily affected by factors such as oxidation and photodegradation, leading to instability during storage and use.
The system employs an oil-aqueous biphase design, using vitamin A oil as the core active ingredient, combined with medium-chain triglyceride oil and soybean oil as carriers, and adding monoglycerides to improve interfacial properties. In the aqueous phase, β-cyclodextrin is used as the molecular inclusion material, combined with sodium octenyl succinate starch as a stabilizer. The system is stabilized through molecular inclusion, electrostatic stabilization and steric hindrance mechanisms. Combined with 60 mPa high-pressure homogenization technology, a highly efficient and stable delivery system is formed.
It significantly improves the encapsulation efficiency and water solubility of vitamin A, maintains its stability, has a particle size increase of less than 11%, and a vitamin A retention rate of over 94%, meeting the requirements of industrial production and suitable for functional foods and health products.
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Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of vitamin A preparation, and particularly relates to a liquid preparation containing vitamin A and a preparation method thereof. BACKGROUND
[0002] As an important fat-soluble vitamin, vitamin A mainly exists in two forms in the human body: carotenoids (such as beta-carotene and other vitamin A precursors) of plant origin and retinol and its esterified form (such as preformed vitamin A such as retinol palmitate) of animal origin; as an essential micronutrient for the human body, vitamin A is involved in the regulation of various key physiological functions, and its insufficient intake will lead to a wide range of biological dysfunction; in the visual system, vitamin A is an important raw material for the synthesis of rhodopsin, and its deficiency will lead to night blindness and even blindness; in growth and development, it affects cell differentiation and tissue formation by regulating gene expression; in immune defense, vitamin A maintains the integrity of the epithelial barrier and regulates immune cell function; in addition, it is also involved in the regulation of reproductive function and hematopoietic process.
[0003] Vitamin A deficiency (VAD) is a serious public health challenge worldwide, causing a serious health burden in developing countries, especially in sub-Saharan Africa and Southeast Asia. According to the latest data of the World Health Organization, about 33% of children in sub-Saharan Africa are vitamin A deficient, and 15-20% of pregnant women in South Asia also face this nutritional deficiency problem. This health crisis mainly affects three high-risk groups: infants and young children who are breastfed but have insufficient vitamin A content in breast milk, children who have improper complementary feeding, pregnant women whose nutritional needs surge in the third trimester of pregnancy, and patients with malabsorption diseases such as celiac disease or pancreatic insufficiency; the serious consequences are shocking, according to statistics, 25-50 million children worldwide suffer irreversible visual impairment or even blindness due to vitamin A deficiency every year, and more heart-wrenching is that about half of these blind children will die within a year of diagnosis. In addition, vitamin A deficiency can also significantly increase the fatal risk of infectious diseases, a study by the British Medical Journal confirmed that vitamin A deficiency can increase the mortality rate of measles patients by 50%, and increase the diarrhea-related mortality rate by 40%.
[0004] The degradation of vitamin A mainly occurs through four mechanisms, of which oxidative degradation is the most important pathway. Under the catalysis of light, heat or metal ions, the five conjugated double bonds in the vitamin A molecule will react with oxygen to form a peroxide radical (ROO•) first, and then these radicals will attack other vitamin A molecules to form hydroperoxides (ROOH), and finally degrade into inactive epoxides, short-chain aldehydes (such as β-ionone), ketones or acid compounds. This process has been confirmed by the detection of oxidation products such as 4-oxoretinol and 5,6-epoxyretinol by HPLC-MS; secondly, photochemical degradation under ultraviolet light (UVB / UVA) irradiation can cause vitamin A double bonds to isomerize (from all-trans to cis) or break, producing 9-cis or 13-cis retinol with reduced activity; in the presence of pigments such as chlorophyll, photosensitized oxidation can further accelerate this process through singlet oxygen (¹O2). In addition, thermal degradation is significantly accelerated above 60 ℃, following the Arrhenius equation (activation energy of about 50-80 kJ / mol), which can lead to dehydration of vitamin A to form anhydrous retinol or polymerization. Finally, for retinyl ester compounds, ester bond hydrolysis occurs under acidic or basic conditions to produce free retinol, which is more susceptible to oxidative degradation. To overcome these stability problems, researchers have developed a variety of innovative stabilization strategies: microencapsulation techniques (such as spray drying) can achieve an encapsulation rate of more than 90% by embedding wall materials such as gum arabic-maltodextrin; nanocarrier systems (such as liposomes and solid lipid nanoparticles) use phospholipid bilayer structures to isolate environmental factors, extending the half-life of vitamin A by 3 times; complex antioxidant systems (such as 0.05% vitamin E combined with 0.005% EDTA) significantly slow down the oxidation rate through synergistic effects. These technological advances not only significantly improve the stability of vitamin A in various formulations, but the stability in liquid is not guaranteed to be stable. SUMMARY
[0005] The purpose of the embodiment of the present application is to provide a liquid preparation containing vitamin A and a preparation method thereof, to solve the technical problem of poor sustained stability of vitamin A in various formulations in the prior art.
[0006] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is to provide a preparation method of a liquid preparation containing vitamin A, which specifically comprises the following steps: (1) Oil phase preparation: mix vitamin A oil, medium-chain triglyceride oil, and soybean oil in a container, add monoglyceride, heat and mix to obtain an oil phase; (2) Water phase preparation: mix β-cyclodextrin with distilled water, heat, add sodium octenyl succinate starch and stir to obtain a water phase; (III) Pre-emulsification: The oil phase is poured into the aqueous phase in proportion, sheared and cooled to obtain a crude emulsion; (iv) Homogenization: After homogenizing the crude emulsion, place it in a brown container to obtain a liquid preparation containing vitamin A.
[0007] In one embodiment, In step (1), by weight percentage, vitamin A oil is 5%, medium-chain triglyceride oil is 15%, soybean oil is 10%, and monoglycerides are 1%.
[0008] In one embodiment, In step (a), vitamin A exists in the form of retinol acetate or retinol palmitate, preferably in the form of retinol palmitate.
[0009] In one embodiment, Step (1) The heating temperature is 40-60 ℃, the mixing speed is 300 rpm, and the time is 15 min.
[0010] In one embodiment, In step (ii), the excipients include sugar alcohol, citric acid, and steviol glycosides. By weight percentage, the composition is: β-cyclodextrin 8%, sodium octenyl succinate starch 4%, sugar alcohol 2%, citric acid 1%, steviol glycosides 5%, and distilled water as the remainder. In one embodiment, Step (2) The heating temperature is 50-70 ℃, the stirring speed is 800 rpm, and the time is 30 min.
[0011] In one embodiment, Step (3): The volume ratio of oil phase to water phase is 1:3, the shearing speed is 12000 rpm, and the time is 5 min; the cooling temperature is 40 ℃.
[0012] In one embodiment, Step (iv) Homogenize at a pressure of 60 MPa and a temperature of 38-42 ℃, and repeat the homogenization process 3 times.
[0013] This application also provides a liquid formulation containing vitamin A, prepared using the preparation method of any of the above embodiments.
[0014] This application provides a liquid formulation containing vitamin A and its preparation method. The formulation of this application adopts an oil-aqueous two-phase system design. The oil phase uses vitamin A oil as the core active ingredient, combined with medium-chain triglyceride oil and soybean oil as carriers, and adds monoglycerides to improve interfacial properties. The aqueous phase uses β-cyclodextrin as a molecular inclusion material, combined with sodium octenyl succinate starch as a stabilizer. This combination not only ensures a high encapsulation rate of vitamin A, but also achieves system stability through multiple stabilization mechanisms (molecular inclusion, electrostatic stability, and steric hindrance). Specifically, in this stable system, β-cyclodextrin, with its unique "externally hydrophilic and internally hydrophobic" conical structure, first embeds hydrophobic vitamin A molecules into its hydrophobic cavity through a molecular inclusion mechanism, forming a host-guest inclusion complex. This not only significantly improves the water solubility and encapsulation rate of vitamin A, but also essentially isolates it from the external aqueous environment, giving the system initial stability. Subsequently, sodium octenyl succinate starch was introduced as a highly efficient stabilizer. The large hydrophilic starch chains in its molecule fully extend around the particles, forming a thick hydration layer. Through steric hindrance, it generates physical repulsion between particles, effectively preventing close contact and aggregation of the inclusion complex. At the same time, the octenyl succinate groups introduced into the modified starch molecule impart a negative charge to the entire system after ionization in water. These charged groups form an electric double layer around the particles, generating a strong electrostatic repulsion when the particles approach each other, i.e., electrostatic stabilization. Ultimately, these three mechanisms work synergistically: molecular inclusion achieves the core encapsulation and isolation of the active ingredient, while electrostatic stabilization and steric hindrance together construct an internal and external double barrier against particle aggregation, thus forming a highly efficient and stable delivery system that integrates encapsulation, solubilization, and long-term stability at the microscopic level. The process employs a 60 mPa high-pressure homogenization process three times, providing excellent kinetic stability for the system. Accelerated testing shows a vitamin A retention rate >94% and a particle size increase <11%, confirming that the formulation effectively overcomes the unstable characteristics of vitamin A, such as easy oxidation and photolysis. The proportions of each component in the formulation have been systematically optimized: the 4% emulsifier dosage ensures stability while avoiding excessive thickening; the 1:3 oil-to-water ratio achieves optimal phase distribution; and the 60 mPa homogenization pressure strikes a balance between nano-sizing and avoiding overheating degradation. This design not only meets the feasibility requirements for industrial production, with a wide process window and good repeatability, but also provides a reliable technical solution for the application of vitamin A in functional foods and health products through the synergistic effect of β-cyclodextrin inclusion and nano-emulsification. Detailed Implementation
[0015] To make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, this application will be further described in detail. It should be understood that the specific embodiments described herein are only for explaining this application and are not intended to limit this application.
[0016] Example 1 A method for preparing a liquid preparation containing vitamin A specifically includes the following steps: (I) Preparation of oil phase: According to the weight percentage, 5% vitamin A oil (retinyl palmitate), 15% medium chain triglyceride oil and 10% soybean oil are placed in a beaker and mixed. 1% monoglyceride is added, and the mixture is heated in a water bath at 60 ℃ and magnetically stirred (at 300 rpm) for 15 min until completely dissolved and mixed to obtain the oil phase; (II) Preparation of aqueous phase: According to the weight percentage, 8% of β-cyclodextrin and 80% distilled water were mixed, heated to 70 ℃, and 4% sodium octenyl succinate starch, 2% sugar alcohol, 1% citric acid and 5% steviol glycoside were added. The mixture was stirred at high speed (800 rpm) for 30 min until completely dissolved to obtain the aqueous phase. (III) Pre-emulsification: Pour the oil phase into the aqueous phase at a volume ratio of 1:3, shear at 12000 rpm for 5 min, and cool in a refrigerator to 40 ℃ to obtain a crude emulsion; the oil phase should be added to the aqueous phase slowly, and pre-emulsification must be completed before homogenization; (iv) Homogenization: The homogenizer is set to a pressure of 60 MPa and a temperature of 40 ℃. The crude emulsion is homogenized three times and then placed in a brown container to obtain a liquid preparation containing vitamin A.
[0017] Example 2 The difference between this embodiment and Embodiment 1 is that in step (i), vitamin A exists in the form of retinol acetate, while the rest of the operations are the same.
[0018] Example 3 The difference between this embodiment and embodiment 1 is that in step (i), the heating temperature is 40 ℃, while the rest of the operations are the same.
[0019] Example 4 The difference between this embodiment and embodiment 1 is that in step (ii), the heating temperature is 50 ℃, while the rest of the operation is the same.
[0020] Experimental Example 1 The interference factors of the detection method were verified in five aspects: the form of vitamin A, product pH value, single mineral element, sterilization parameters, and mineral compound compatibility. The relevant schemes and results are shown in Table 1. Table 1. Experimental scheme and results for verifying interference factors
[0021] Analysis of the verification results of the five types of interference factors in Table 1: 1) Scheme 1-2 proves that during the product acceleration process, the stability of vitamin A palmitate retinol in liquid products is significantly better than that of vitamin A retinol acetate, which can meet the stability requirements within the product's shelf life. 2) Scheme 2-3 proves that the vitamin A test results in the product were not abnormal under different pH conditions; 3) Schemes 4-6 demonstrate that different mineral elements have different effects on vitamin A content. Among them, the vitamin A content detection in Schemes 4 and 5 showed no abnormalities, while Scheme 6 showed a faster decrease in vitamin A content during the accelerated test on day 20. Magnesium gluconate interfered with the detection of vitamin A. 4) Scheme 7-8 demonstrates that the vitamin A content does not change significantly under different sterilization parameters, proving that sterilization temperature is not related to abnormal vitamin A detection. 5) Schemes 9-11 demonstrate the effect of different mineral combinations on vitamin A content. In Scheme 10, the trend of vitamin A content change is basically consistent with the results of single-factor effects of calcium citrate and zinc citrate. In Scheme 11, the trend of vitamin A content change is basically consistent with the results of single-factor effects of magnesium gluconate. The trend of vitamin A content change in Scheme 9 is more significant than that in all other schemes.
[0022] In summary, vitamin A palmitate is more stable than vitamin A acetate; pH in the product system has no effect on vitamin A detection results; in the single-factor mineral experiment, magnesium gluconate affects vitamin A detection with prolonged storage time; in the mineral compatibility verification, the combination of calcium citrate and magnesium gluconate has a greater impact on vitamin A detection than magnesium gluconate alone; the stability verification results are consistent with the literature and patent conclusions, confirming that the combination of calcium citrate and magnesium gluconate will cause the product to form a special colloidal spatial structure, and that the complexation of gluconate with vitamin A will affect the detection results.
[0023] Experiment Example 2 Stability test: Test conditions: Accelerated conditions: 60 ℃±1 ℃, 75 % RH; Long-term conditions at room temperature: 37 ℃±2 ℃, 60 %RH; Irradiation conditions: 4500 lux; The liquid preparation containing vitamin A prepared in Example 1 was used for testing. The test results are shown in Table 2. All data in this experiment are the average of three repeated determinations, and the relative standard deviation is <5%.
[0024] Table 2 Stability test results
[0025] Experimental Example 3 Centrifugation experiment: Centrifugation conditions were 3000 rpm for 15 min, and no stratification was observed in the results; Freeze-thaw cycle experiment: The freeze-thaw cycle conditions were -20~25 ℃ for 3 cycles, and the system properties were stable.
[0026] This application provides a liquid formulation containing vitamin A and its preparation method, comprising the following steps: mixing vitamin A oil, medium-chain triglyceride oil, and soybean oil in a container; adding monoglycerides and heating to mix, thus obtaining an oil phase; mixing β-cyclodextrin with distilled water, heating, adding sodium octenyl succinate starch and excipients, and stirring to obtain an aqueous phase; pouring the oil phase into the aqueous phase in a proportion, shearing, and cooling to obtain a crude emulsion; homogenizing the crude emulsion to obtain a liquid formulation containing vitamin A; the formulation of this application uses an oil-aqueous two-phase system. The design incorporates vitamin A oil as the core active ingredient in the oil phase, combined with medium-chain triglyceride oil and soybean oil as carriers, and adds monoglycerides to improve interfacial properties. The aqueous phase uses β-cyclodextrin as the molecular inclusion material, combined with sodium octenyl succinate starch as a stabilizer. This combination ensures high encapsulation efficiency of vitamin A and achieves system stability through multiple stabilization mechanisms (molecular inclusion, electrostatic stability, and steric hindrance). The process employs 60 mPa high-pressure homogenization three times to provide excellent kinetic stability. Accelerated testing (37...) (℃ / 28 days) showed a vitamin A retention rate of >94% and a particle size increase of <11%, confirming that the formulation can effectively overcome the unstable characteristics of vitamin A such as easy oxidation and photolysis. The ratio of each component in the formulation has been systematically optimized: the amount of 4% emulsifier ensures stability while avoiding excessive thickening; the 1:3 oil-to-water ratio achieves the optimal phase distribution; the 60 mPa homogenization pressure achieves a balance between nano-sizing and avoiding overheating degradation. This design not only meets the feasibility requirements of industrial production, with a wide process window and good repeatability, but also provides a reliable technical solution for the application of vitamin A in functional foods and health products through the synergistic effect of β-cyclodextrin inclusion and nano-emulsification.
[0027] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A method for preparing a liquid preparation containing vitamin A, characterized in that, Specifically, the following steps are included: (I) Preparation of oil phase: Vitamin A oil, medium chain triglyceride oil and soybean oil are placed in a container and mixed. Monoglycerides are added and heated to mix to obtain the oil phase. (II) Preparation of aqueous phase: β-cyclodextrin is mixed with distilled water, heated, and sodium octenyl succinate starch and excipients are added and stirred to obtain the aqueous phase; (III) Pre-emulsification: The oil phase is poured into the aqueous phase in proportion, sheared and cooled to obtain a crude emulsion; (iv) Homogenization: The crude emulsion is homogenized and placed in a brown container to obtain a liquid preparation containing vitamin A.
2. The method for preparing a liquid preparation containing vitamin A according to claim 1, characterized in that, In step (1), by weight percentage, vitamin A oil is 5%, medium-chain triglyceride oil is 15%, soybean oil is 10%, and monoglycerides are 1%.
3. The method for preparing a liquid preparation containing vitamin A according to claim 1, characterized in that, In step (a), vitamin A exists in the form of retinol acetate or retinol palmitate.
4. The method for preparing a liquid preparation containing vitamin A according to claim 1, characterized in that, The heating temperature in step (1) is 40-60 ℃, the mixing speed is 300 rpm, and the time is 15 min.
5. The method for preparing a liquid preparation containing vitamin A according to claim 1, characterized in that, In step (ii), the excipients include sugar alcohols, citric acid, and steviol glycosides.
6. The method for preparing a liquid preparation containing vitamin A according to claim 5, characterized in that, By weight percentage, β-cyclodextrin is 8%, sodium octenyl succinate starch is 4%, sugar alcohol is 2%, citric acid is 1%, steviol glycosides are 5%, and distilled water is the balance.
7. The method for preparing a liquid preparation containing vitamin A according to claim 1, characterized in that, In step (ii), the heating temperature is 50-70 ℃, the stirring speed is 800 rpm, and the time is 30 min.
8. The method for preparing a liquid preparation containing vitamin A according to claim 1, characterized in that, In step (iii), the volume ratio of the oil phase to the water phase is 1:3, the shearing speed is 12000 rpm, the time is 5 min, and the cooling temperature is 40 ℃.
9. The method for preparing a liquid preparation containing vitamin A according to claim 1, characterized in that, In step (iv), the homogenization pressure is 60 MPa, the temperature is 38-42 ℃, and the homogenization is performed 3 times.
10. A liquid preparation containing vitamin A, characterized in that, It is prepared by the preparation method described in any one of claims 1-9.