Fish oil composite capsule prepared by rTGA technology and application of fish oil composite capsule in cardiovascular and bone health
The preparation of high-purity fish oil and vitamin D3 compound capsules using rTGA technology solves the problems of low purity and poor stability of existing products, achieving synergistic improvement in cardiovascular and bone health and providing safe and reliable dual health benefits.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-01-14
- Publication Date
- 2026-04-07
AI Technical Summary
Existing fish oil and vitamin D3 compound products have low purity and poor stability, lack synergistic effect verification, and traditional packaging technology cannot guarantee long-term stability, resulting in insignificant health effects or accumulation of harmful substances.
High-purity fish oil was prepared using multi-stage molecular distillation (rTGA) technology and compounded with vitamin D3 in a specific ratio. Combined with double-layer microcapsule encapsulation technology, including coagulation and enteric coating, a stable capsule product was formed.
It achieves a synergistic effect between high-purity fish oil and vitamin D3, significantly improving cardiovascular and bone health indicators, enhancing product stability and safety, and ensuring the effectiveness of active ingredients during storage and absorption.
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Figure CN121795616A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of functional foods and dietary supplements, specifically to a fish oil compound capsule prepared using specific purification and compounding techniques, and more particularly to a dietary supplement capsule made from high-purity fish oil based on molecular distillation (refined triglyceride, rTGA) and scientifically combined with vitamin D3, and produced using double-layer encapsulation technology, and its application in synergistically promoting cardiovascular and bone health. Background Technology
[0002] Omega-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been widely proven to possess various physiological activities, including regulating blood lipids, anti-inflammation, improving vascular endothelial function, and inhibiting platelet aggregation. These activities are significant for preventing cardiovascular diseases (CVD) such as atherosclerosis and coronary heart disease. On the other hand, vitamin D3, a key fat-soluble vitamin, primarily functions to promote the absorption of calcium and phosphorus in the intestines, which is crucial for maintaining bone health and preventing osteoporosis.
[0003] Currently, most mainstream products on the market are either single-ingredient fish oil softgels or vitamin D3 supplements. An increasing number of consumers are combining both in hopes of achieving dual health benefits. However, existing simple physical compounding or "bundled sales" models have significant drawbacks: First, traditional fish oil has low purity (EPA+DHA content is typically 30%-70%) and contains a certain amount of cholesterol, oxidation products, and potential environmental pollutants (such as PCBs, dioxins, heavy metals, etc.), raising concerns about its safety and efficacy with long-term use. Second, the polyunsaturated fatty acids in fish oil are highly susceptible to oxidative rancidity, leading to the loss of active ingredients and unpleasant flavors; vitamin D3 is also unstable to light and oxygen. Conventional softgel encapsulation technology cannot simultaneously ensure the long-term stability of both. Furthermore, there is a lack of systematic scientific research and product validation regarding the synergistic effect between EPA / DHA and vitamin D3, and what the optimal ratio is. Inappropriate ratios may prevent the expected "1+1>2" health benefits from being achieved, or even affect the effectiveness due to improper dosage.
[0004] Molecular distillation is a separation technique performed under high vacuum, with operating temperatures far below the boiling point of the material, making it particularly suitable for purifying heat-sensitive and high-boiling-point materials. Fish oil processed by multi-stage molecular distillation (rTGA) can efficiently remove the aforementioned harmful impurities, significantly increase the concentration of EPA and DHA (up to over 75%), and substantially reduce the peroxide value, thereby obtaining high-purity, highly stable, and high-quality fish oil raw materials. Developing a complex dietary supplement that can clearly, synergistically, and safely target the cardiovascular and skeletal health systems by utilizing this advanced raw material through scientific formulation with vitamin D3 and innovative stabilization technology is the core direction for enhancing the technological content and market value of such products. Summary of the Invention
[0005] To address the problems of low purity, poor stability, and lack of synergistic effect verification and effective stabilization methods when fish oil is combined with vitamin D3 in existing technologies, this invention provides a fish oil compound dietary supplement capsule based on rTGA technology, its preparation method, and its application.
[0006] The primary objective of this invention is to provide a method for preparing high-quality fish oil compound capsules. This method ensures the extremely high purity and safety of raw materials through rTGA technology, achieves synergistic effects of active ingredients through specific ratio formulation, and solves the stability problem of the compound system through an innovative double-layer encapsulation process.
[0007] Another object of the present invention is to provide fish oil compound dietary supplement capsules prepared by the above method.
[0008] Another object of the present invention is to provide a new application of the above-mentioned capsules in the preparation of dietary supplements for simultaneously improving cardiovascular health indicators and bone health indicators.
[0009] To achieve the above objectives, the present invention adopts the following technical solution:
[0010] A method for preparing fish oil compound dietary supplement capsules based on rTGA technology includes the following steps:
[0011] S1. Preparation of high-purity rTGA fish oil base: The fish oil raw material was purified using multi-stage molecular distillation. First, the raw material underwent degumming and deacidification pretreatment. Then, the crude fish oil was subjected to two-stage molecular distillation. The first stage removed light components such as free fatty acids at a relatively low temperature (120-160℃) and pressure (0.1-1.0 Pa). The second stage was distilled at a higher temperature (180-220℃) and lower pressure (0.01-0.1 Pa), collecting the fraction rich in Omega-3. The final product was a high-purity rTGA fish oil base with a total EPA+DHA content ≥75%, a peroxide value (PV) ≤1.0 meq / kg, anisidine value (AV) ≤5.0, and extremely low (≤0.5%) content of long-chain impurities (such as C28:6).
[0012] S2. Formulation of the core contents: Using the aforementioned rTGA fish oil base as a carrier, vitamin D3 is added in a specific synergistic ratio. The preferred ratio is: per 1000mg of fish oil base, containing 350-450mg of EPA, 250-350mg of DHA, and 15-25 μg (600-1000 IU) of vitamin D3. Simultaneously, a complex antioxidant (such as natural vitamin E and rosemary extract, total addition 0.05%-0.2% w / w) and trace amounts of natural flavoring (such as lemon oil, 0.01%-0.05% w / w) are added. The mixture is thoroughly homogenized under nitrogen or argon protection to form a homogeneous and stable oily content.
[0013] S3. Double-Layer Microencapsulation: The core material is encapsulated in two steps to enhance stability. Step 1: Complex Coagulation Method: The core material (oil phase) is emulsified with an aqueous phase containing gelatin and gum arabic. The pH is adjusted to near the isoelectric point (4.0-4.5), allowing the two colloids to co-deposit on the oil droplet surface to form a dense first protective layer. After cross-linking and curing, primary microcapsules are obtained. Step 2: Enteric Coating: The primary microcapsules are sprayed with an enteric coating solution of acrylic resin (such as Eudragit L100) using fluidized bed technology to form a second coating layer. The coating weight gain is controlled at 5%-10%. This coating resists gastric acid, ensuring the release of active ingredients in the neutral intestinal environment, improving absorption and protecting vitamin D3.
[0014] S4. Capsule Forming: The above-mentioned encapsulated granules are mixed with an appropriate amount of filler and filled into gelatin or plant gum soft capsule shells. After processes such as granulation, shaping, drying and polishing, the final capsule product is obtained.
[0015] This invention also seeks protection for fish oil complex dietary supplement capsules based on rTGA technology prepared by the above method.
[0016] Furthermore, this invention claims protection for the use of the aforementioned fish oil complex dietary supplement capsules in the preparation of dietary supplements for simultaneously improving cardiovascular and bone health indicators in mammals (including humans). The improvement in cardiovascular health indicators is preferably manifested as a significant reduction in serum triglyceride (TG) and total cholesterol (TC) levels; the improvement in bone health indicators is preferably manifested as a significant increase in serum 25-hydroxyvitamin D [25(OH)D] levels and improved bone mineral density (BMD).
[0017] The present invention has the following beneficial effects:
[0018] High quality from the source, safe and reliable: Using the rTGA core technology, the purity of fish oil is improved to an industry-leading level (≥75%) from the source, and risky substances such as cholesterol, heavy metals, and persistent organic pollutants are effectively removed, making the product significantly safer than ordinary fish oil.
[0019] Scientific formulation, synergistic effect: The optimal synergistic ratio of EPA, DHA and vitamin D3 was determined through experiments. Animal experiments have confirmed that the compound in this specific ratio is significantly more effective than using the same dose of fish oil or vitamin D3 alone, or using products with non-optimal ratios, in lowering blood lipids (TG, TC) and increasing bone calcium and bone density, achieving a true "synergistic effect".
[0020] Advanced technology, stable and long-lasting effect: The innovative "re-coagulation + enteric coating" double-layer encapsulation system provides dual physicochemical protection for the highly oxidizable fish oil and photosensitizing vitamin D3. The inner wall material effectively isolates oxygen and prevents oxidative rancidity during storage; the outer enteric coating ensures that the active ingredients are protected from gastric acid and are released directly into the small intestine, the main absorption site, greatly improving bioavailability and product shelf life.
[0021] With a clear function and targeting dual health: The product of this invention is not a simple combination, but a dietary supplement developed based on clear scientific evidence that can effectively intervene in two major chronic health problems (cardiovascular disease and osteoporosis) at the same time. It provides a precise and efficient nutritional solution for people with complex health needs (such as middle-aged and elderly people and postmenopausal women), and has broad market application prospects. Attached Figure Description
[0022] Figure 1 This is a flowchart illustrating the preparation process of fish oil compound dietary supplement capsules provided in an embodiment of the present invention.
[0023] Figure 2 This is a schematic diagram of the double-layer microcapsule structure of the active ingredient in the capsules of this invention. Detailed Implementation
[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.
[0025] Example 1: Preparation of fish oil compound dietary supplement capsules
[0026] rTGA Purification: 100 kg of deep-sea fish oil raw material (initial EPA approximately 18%, DHA approximately 12%) was degummed and deacidified to obtain approximately 95 kg of crude oil. The crude oil was pumped into a first-stage molecular still and distilled at 140℃ and 0.5 Pa to remove light components. The distillate was collected and pumped into a second-stage molecular still and purified at 200℃ and 0.05 Pa, collecting 62 kg of the target fraction. Detection indicators: EPA content 41.5%, DHA content 31.2%, total EPA+DHA content 85.8%, PV=0.8 meq / kg, AV=3.5, C28:6 not detected (<0.1%). This is the high-purity rTGA fish oil base.
[0027] Core Material Formulation: Weigh 95.74 kg of the above-mentioned fish oil base (as a baseline, approximately 1000 mg per capsule). Add 1.9 g of vitamin D3 powder (1.0 MIU / g) (providing 20 μg / 1000 mg oil), 0.1 kg of natural vitamin E, 0.05 kg of rosemary extract, and 0.02 kg of lemon oil. In a reaction vessel continuously purged with nitrogen, homogenize and stir at 200 rpm for 1 hour at 45°C to obtain a homogeneous and transparent core material mixture.
[0028] Double-layer embedding:
[0029] Re-coagulation: A 10% gelatin aqueous solution and a 5% gum arabic aqueous solution were prepared and mixed at a mass ratio of 2:1 as the aqueous phase. The aqueous phase was mixed with the core material at a 1:1 (w / w) ratio and circulated three times at 50 MPa using a high-pressure homogenizer at 45°C to form a homogeneous O / W emulsion. The pH of the emulsion was adjusted to 4.2 with a 10% acetic acid solution, and the mixture was slowly stirred for 30 minutes to induce re-coagulation. An appropriate amount of glutaraldehyde was added for cross-linking and curing for 1 hour. Subsequently, spray drying was performed (inlet air temperature 180°C, outlet air temperature 85°C) to obtain primary microcapsule powder.
[0030] Enteric coating: The primary microcapsule powder was placed in a fluidized bed coating machine and preheated to 35°C. An 8% (w / v) solution of Utec L100 acrylic resin in ethanol was sprayed in, and the inlet air temperature, spray rate, and atomization pressure were controlled to achieve a coating weight gain of approximately 8%. After coating, the microcapsule particles were dried at 40°C for 2 hours to obtain enteric-coated microcapsule particles.
[0031] Saccharification: Coated microcapsule particles are mixed with a small amount of refined medium-chain triglyceride (MCT) oil to adjust the flowability, and then filled into gelatin shells using a fully automatic soft capsule saccharification machine to produce oval soft capsules with a net content of 1200mg per capsule. After shaping, drying, polishing, and sorting, the finished product is obtained.
[0032] Examples 2-4: Preparation of Capsules with Different Formulations
[0033] Following the preparation process of Example 1, only the EPA / DHA ratio in the rTGA fish oil base was changed (by adjusting the distillation process parameters) and the amount of vitamin D3 added, to prepare the products of Examples 2-4. The contents of their key active ingredients are shown in Table 1. Example 4 serves as a comparative example with a relatively low vitamin D3 content.
[0034] Table 1. Content of key active ingredients in products from Examples 1-4 (per capsule)
[0035]
[0036] Experiment Example 1: Verification of Synergistic Efficacy of Products (Animal Experiment)
[0037] Experimental Design: Eighty healthy SD rats were randomly divided into eight groups (n=10): Group A (normal control group, normal diet), Group B (high-fat model group, high-fat diet), Group C (high-fat + ordinary fish oil group, administered with commercially available 50% pure fish oil containing an equivalent total amount of EPA + DHA), Group D (high-fat + vitamin D3 group, administered with an equivalent dose of pure vitamin D3 oil), Group E (high-fat + product of Example 1), Group F (high-fat + product of Example 2), Group G (high-fat + product of Example 3), and Group H (high-fat + product of Example 4). All groups were administered the drugs by gavage once daily for eight consecutive weeks.
[0038] Detection indicators: At the end of the experiment, blood samples were collected to detect serum TG, TC, and 25(OH)D concentrations. After euthanizing the animals, the right femur was harvested, and the bone mineral density (BMD) of the midshaft of the femur was measured using dual-energy X-ray absorptiometry.
[0039] Results analysis:
[0040] Cardiovascular effects: Compared with the high-fat model group (Group B), all intervention groups (Group CH) showed varying degrees of decrease in TG and TC. Among them, the product groups of Examples 1, 2, and 3 of this invention (Groups E, F, and G) showed the most significant decrease (P<0.01), and were significantly better than the groups using ordinary fish oil alone (Group C) or vitamin D3 alone (Group D) (P<0.05). The effect of Example 4 (Group H) was between that of the single-component groups and the preferred examples of this invention.
[0041] Skeletal effects: Similar trends were observed in increasing serum 25(OH)D levels and femoral BMD. The product groups in Examples 1, 2, and 3 showed the best effects, significantly superior to group D which only supplemented with vitamin D3 (P<0.05), indicating that the presence of high-purity fish oil enhanced the promoting effect of vitamin D3 on calcium metabolism and bone formation. The effect of group 4 was weaker than the previous three.
[0042] Conclusion: The fish oil compound capsules of the present invention (especially the formulations of Examples 1-3) exhibit a clear synergistic effect in regulating blood lipids and improving bone health, verifying the effectiveness of their scientific formulation.
[0043] Experiment Example 2: Accelerated Stability Test of Products
[0044] The product of Example 1 of this invention and a commercially available brand of ordinary fish oil soft capsules (labeled EPA+DHA 30%) were placed in a constant temperature and humidity chamber at 40°C and 75% relative humidity for accelerated stability testing. Samples were taken and tested at the end of 0, 1, 2, and 3 months.
[0045] Peroxide value (PV): After 3 months, the PV of commercially available fish oil rose sharply from the initial 3.5 meq / kg to 15.2 meq / kg, far exceeding the industry safety limit (usually ≤10 meq / kg). In contrast, the PV of the product of this invention only slowly increased from 0.8 meq / kg to 2.1 meq / kg, demonstrating excellent oxidative stability.
[0046] Vitamin D3 content: determined by high performance liquid chromatography. After 3 months, the retention rate of commercially available vitamin D3 drops was 78%, while the retention rate of vitamin D3 in the product of this invention was as high as 96%.
[0047] Conclusion: The double-layer microencapsulation technology (complex cohesive wall material + enteric coating) of this invention can effectively protect fish oil and vitamin D3, prevent their oxidative decomposition and potency loss during storage, and ensure the quality and efficacy of the product throughout its shelf life.
[0048] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.
[0049] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.
Claims
1. A method for preparing fish oil compound dietary supplement capsules based on rTGA technology, characterized in that, Includes the following steps: S1. The fish oil raw material is purified by multi-stage molecular distillation to prepare rTGA high-purity fish oil base, with a total EPA and DHA content of not less than 75% and a peroxide value of not more than 1.0 meq / kg; S2. Using the rTGA high-purity fish oil base as a carrier, vitamin D3 and a composite antioxidant are added according to a preset synergistic ratio and homogenized to form the core material of the contents under the protection of an inert gas. S3. The contents core material is encapsulated using a double-layer encapsulation technology: first, an inner gelatin-gum arabic composite wall material is formed by a complex coagulation method, and then an outer enteric coating is formed by a coating process to obtain encapsulated particles; S4. The embedded particles are filled into soft capsule shells, and after molding and drying, the fish oil compound dietary supplement capsules are obtained.
2. The preparation method according to claim 1, characterized in that, The multi-stage molecular distillation technique described in step S1 specifically includes: The fish oil raw material was subjected to degumming and deacidification pretreatment in sequence to obtain crude fish oil. The crude fish oil was subjected to first-stage molecular distillation under the following conditions: temperature 120-160℃, system pressure 0.1-1.0Pa, to separate the light components. The first-stage distillate is subjected to a second-stage molecular distillation under the following operating conditions: temperature 180-220℃, system pressure 0.01-0.1 Pa. The target fraction rich in Omega-3 is collected, which is the rTGA high-purity fish oil base. The rTGA high-purity fish oil base must also meet the following requirements: docosahexaenoic acid content ≤ 0.5%, and anisidine value ≤ 5.
0.
3. The preparation method according to claim 1, characterized in that, The preset synergistic ratio mentioned in step S2 is as follows: each 1000mg of the rTGA high-purity fish oil base contains 350-450mg of EPA, 250-350mg of DHA, and 15-25μg of vitamin D3.
4. The preparation method according to claim 1 or 3, characterized in that, The compound antioxidant mentioned in step S2 is a mixture of natural vitamin E and rosemary extract, and its total addition amount accounts for 0.05% to 0.2% of the total weight of the core material of the contents; step S2 also adds natural fragrance accounting for 0.01% to 0.05% of the total weight of the core material of the contents.
5. The preparation method according to claim 1, characterized in that, The specific process of using the double-layer embedding technology in step S3 includes: The contents core material is emulsified with an aqueous phase containing gelatin and gum arabic at 40-50°C to form an oil-in-water primary emulsion. The pH of the promulgated emulsion was adjusted to 4.0-4.5, and a first layer of composite wall material was formed on the surface of the oil droplets through a complex coagulation reaction. After curing, primary microcapsules were obtained. The primary microcapsules are placed in a fluidized bed and sprayed with an acrylic resin enteric coating solution to form a second coating layer. The weight gain of the enteric coating is 5%-10% of the weight of the primary microcapsules.
6. A fish oil compound dietary supplement capsule based on rTGA technology, prepared by any one of claims 1 to 5.
7. The use of the fish oil compound dietary supplement capsule as described in claim 6 in the preparation of a dietary supplement for simultaneously improving cardiovascular health indicators and bone health indicators.
8. The application according to claim 7, characterized in that, The cardiovascular health indicators include serum triglyceride and total cholesterol levels; the bone health indicators include serum 25-hydroxyvitamin D levels and bone mineral density.