DHA micro-droplet pills and preparation method thereof

Abstract

The present application relates to the technical field of small drop pills, and particularly relates to DHA small drop pills and a preparation method thereof, the small drop pills comprising a core liquid and a rubber skin covering the core liquid, the core liquid comprising the following components in parts by weight: DHA algal oil 75-85 parts; sweet orange oil 5-25 parts; the rubber skin comprising the following components in parts by weight: gelatin 18-40 parts; glycerol 8-12 parts; water 66-100 parts, the gelatin is prepared by using multiple animal sources as collagen, and a capsule structure with both strength and elasticity is successfully constructed by combining with precisely controlled crosslinking degree. Experimental results show that the breaking force of the best embodiment is as high as 895±30g, which is increased by 37.7% compared with a traditional formula. The enhanced mechanical strength ensures that the small drop pills can burst instantly in the oral cavity, release the internal DHA, and provide an excellent oral experience.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of small drop pills, in particular to a DHA small drop pill and a preparation method thereof. BACKGROUND

[0002] DHA is an important component of brain gray matter, accounting for about 97% of omega-3 fatty acids in the brain. It plays a key role in the growth of nerve cells and the formation of synapses, helping to improve learning, memory and thinking ability. It has different health benefits for different populations. In recent years, with people's increasing attention to health, the demand for DHA supplements has been increasing.

[0003] At present, the most common DHA preparation on the market is mainly in the form of soft capsules. Soft capsules, as a dosage form applied to carry oily materials in the market earlier, are a compression molding process, with part of the raw materials exposed outside, thick and large size of the capsule, not easy to swallow, and poor market acceptance. In recent years, a small drop pill dosage form of "one-piece pill" is slowly emerging in the market. The core of this dosage form is that in the production process, using the structure of double-layer nozzle, the algal oil directly enters the capsule skin to form a seamless drop pill in the double-layer nozzle, which is instantly wrapped and formed into a complete pill. The process does not contact oxygen, avoiding the invasion of oxygen and external impurities, thereby maintaining the content of DHA and avoiding the problem of increased fishy smell caused by oxidation. It also has novel and interesting features such as mini dosage form, thin and fast-dissolving skin, strong oral explosion, etc., which are deeply loved by adults and children.

[0004] However, traditional DHA small drop pill preparations face many challenges. For example, low efficiency, slow dissolution of pills, poor temperature resistance, uneven pill size, etc., which to some extent restrict its large-scale production and wide application.

[0005] In view of the above problems, it is urgent to develop a new type of DHA preparation which can effectively improve the stability of DHA, significantly improve its bioavailability, and also consider the sensory quality and production efficiency of the product. The present application is proposed to solve this technical problem. SUMMARY

[0006] The present application provides a DHA small drop pill and a preparation method thereof, which successfully solves the above technical problems through innovative formula design and process optimization. Specifically, the present application realizes the comprehensive improvement of the taste, stability, bioavailability, etc. of DHA small drop pills by using different animal sources as collagen, applying complex enzyme preparations, multiple modification treatments to prepare gelatin, and improving the drop pill process.

[0007] The content of the present application is as follows: a DHA small drop pill, the small drop pill comprises a core liquid and a capsule skin covering the core liquid, wherein:

[0008] The core liquid comprises the following components by weight:

[0009] DHA algal oil 75-85 parts;

[0010] Sweet orange oil 5-25 parts;

[0011] The rubber skin comprises the following components by weight:

[0012] Gelatin 18-40 parts;

[0013] Glycerol 8-12 parts;

[0014] Water 66-100 parts.

[0015] Preferably, the gelatin is prepared from the following raw materials by weight:

[0016] Pig bone 15-25 parts;

[0017] Pig skin 15-25 parts;

[0018] Cow bone 15-25 parts;

[0019] Cow skin 15-25 parts;

[0020] Fish skin 10-20 parts;

[0021] Fish scales 10-20 parts.

[0022] The preparation method of the gelatin comprises the following steps:

[0023] (1) Pretreatment of raw materials:

[0024] a) After cleaning and degreasing the pig bone and cow bone, grind them to 3-5 mm particles using a food-grade bone grinder, soak them in a 0.5-1% food-grade citric acid solution for 6-8 hours, and then rinse them with pure water until the pH is 6.5-7.0;

[0025] b) After cleaning and degreasing the pig skin and cow skin, cut them into 1-2 cm pieces, soak them in a 0.2-0.4% food-grade sodium bicarbonate solution for 3-4 hours, and then rinse them with pure water until the pH is 6.5-7.0;

[0026] c) After cleaning and degreasing the fish skin and fish scales, treat them with a 0.1-0.2% food-grade ascorbic acid solution for 2-3 hours, and then rinse them with pure water until the pH is 6.5-7.0;

[0027] (2) Enzymatic pretreatment:

[0028] Mix the pretreated raw materials according to the ratio, add 6 times the weight of pure water, and adjust the pH to 6.8-7.2;

[0029] Add 0.15-0.25% of complex enzyme preparation, the composition of which is:

[0030] Enzymatic hydrolysis at 44-46°C for 3-3.5 hours, with stirring every 30 minutes for 2-3 minutes each time;

[0031] (3) Enzyme inactivation:

[0032] Slowly adjust the pH to 7.4-7.6, quickly raise the temperature to 62-64°C using a plate heat exchanger and maintain for 12-15 minutes to ensure complete enzyme inactivation;

[0033] (4) Gelatin extraction:

[0034] Transfer the enzymatically hydrolyzed mixture to a multi-stage extraction tank with a temperature gradient, with a total extraction time of 2-2.5 hours:

[0035] a) First stage: 64-66°C, 30-40 minutes;

[0036] b) Second stage: 68-70°C, 40-50 minutes;

[0037] c) Third stage: 72-74°C, 50-60 minutes;

[0038] After the end of each stage of extraction, perform 5 minutes of low-frequency ultrasonic treatment (frequency 20-25 kHz, power 300-400 W);

[0039] (5) Separation and purification:

[0040] Use a combined separation technique of two-step centrifugation and one-step membrane filtration:

[0041] a) Primary centrifugation: 5000-5500 rpm, 25 minutes;

[0042] b) Fine filtration: use ceramic membranes with a 100 kDa molecular weight cut-off for cross-flow filtration, transmembrane pressure difference 0.1-0.2 MPa;

[0043] c) Secondary centrifugation: 6000-6500 rpm, 20 minutes;

[0044] (6) Concentration:

[0045] Concentrate the gelatin solution using a two-stage ultrafiltration system:

[0046] a) First stage: use polyether sulfone membranes with a 15 kDa molecular weight cut-off, operating pressure 0.3-0.4 MPa;

[0047] b) Second stage: use polyvinylidene fluoride membranes with a 5 kDa molecular weight cut-off, operating pressure 0.4-0.5 MPa;

[0048] The final gelatin solution concentration is controlled to be 20-22%;

[0049] (7) Modification treatment:

[0050] (8) Drying:

[0051] Low-temperature vacuum spray drying technology is adopted:

[0052] a) Inlet temperature: 75-78℃

[0053] b) Outlet temperature: 48-52℃

[0054] c) Atomization pressure: 0.22-0.26MPa

[0055] d) Vacuum degree: 60-80Pa

[0056] e) Drying medium: food-grade nitrogen

[0057] (9) Crushing and screening:

[0058] a) Crushed using a low-temperature airflow crusher, with the feed temperature controlled to be 10-15℃

[0059] b) Passed through a 100-mesh stainless steel screen

[0060] c) Dust removal treatment was performed using a food-grade electrostatic dust collector

[0061] d) Near-infrared spectroscopy was used to detect the purity of the gelatin, ensuring that the purity is ≥98%.

[0062] As a preferred, the complex enzyme preparation includes collagenase, papain, neutral protease and alkaline protease, wherein the activity of collagenase is ≥200000 U / g, 40-50%; the activity of papain is ≥600000 U / g, 30-40%; the activity of neutral protease is ≥100000 U / g, 15-20%; the activity of alkaline protease is ≥200000 U / g, 5-10%.

[0063] As a preferred, the first level of the two-stage ultrafiltration system has a molecular weight cut-off of 10000 Da, and the second level has a molecular weight cut-off of 3000 Da.

[0064] As a preferred, the modification treatment includes the following steps:

[0065] (1) 0.4-0.8% citric acid and 0.1-0.3% lactic acid are added to the concentrated solution and stirred uniformly;

[0066] (2) 0.2-0.4% sodium hyaluronate and 0.1-0.3% chitosan are added and stirred for 20-25 minutes;

[0067] (3) Adjust the pH to 6.9-7.3.

[0068] The preparation method of the DHA small pellet pill comprises the following steps:

[0069] (1) Preparation of core liquid: 75-85 parts of DHA algal oil and 5-25 parts of sweet orange oil are mixed and stirred uniformly for 30 minutes to obtain a uniform core liquid;

[0070] (2) Preparation of gelatin solution: 66-100 parts of water is poured into a gelatinizing tank and heated to 70-80°C, 18-40 parts of gelatin is dissolved in the water, 8-12 parts of glycerol is added, and stirring is performed until the gelatin is completely dissolved and the gelatin solution is clear and transparent. Then vacuum degassing is performed at 80-85°C for 8-12 minutes, and the solution is kept warm for standby;

[0071] (3) Dropping is performed by using high-frequency pulse jet technology; the gelatin solution and the core liquid form a concentric flow column in a coaxial double-layer nozzle, the core liquid is in the inner layer, and the gelatin solution is in the outer layer. A number of synchronous pulse forces are applied to the concentric flow column along the circumferential direction of the concentric flow column to cut the concentric flow column into a string of beads;

[0072] (4) The dropped pills are immersed in capric and caprylic acid glycerol ester, and are shaped at 5°C for 4 hours;

[0073] (5) Separation is performed by using low-temperature centrifugal technology: the shaped small pellet pills are placed in a low-temperature environment at 5-10°C, and are centrifuged at a speed of 1500-2000 rpm for 5-8 minutes to separate the small pellet pills and the residual cooling medium;

[0074] (6) Vacuum microwave drying is performed: the separated small pellet pills are placed in a vacuum microwave drying device, the microwave power is 200-300 W, the vacuum degree is 50-100 Pa, the temperature is set to 25°C, the drying time is 15-20 minutes, and the intermittent mode (10 seconds on and 5 seconds off) is adopted to control the final water content of the product to be below 3%;

[0075] (7) Surface treatment is performed by using low-temperature plasma technology: the dried small pellet pills are placed in a low-temperature plasma treatment device, argon gas is used as the working gas, the gas flow is 20-30 sccm, the radio frequency power is 50-100 W, the treatment pressure is 10-50 Pa, the treatment time is 20-30 seconds, and the treatment temperature is controlled at 25-35°C;

[0076] (8) Screening is performed: an ultrasonic wave assisted vibration screening machine is used, the screen mesh aperture is 6.0±0.2 mm, the vibration frequency is 50-60 Hz, and the screening time is 2-3 minutes;

[0077] (9) Nitrogen filling packaging is performed.

[0078] As preferred, the parameters of the high-frequency pulse jet technology are as follows:

[0079] The temperature of the rubber solution is controlled at 80-85 DEG C, the flow rate is 6.0-8.0 mL / min; the temperature of the core solution is 45-50 DEG C, the flow rate is 3.0-4.0 mL / min; the nozzle vibration frequency is 150-200 Hz, the nozzle aperture is 0.3-0.5 mm, and the drop height is 20-30 cm.

[0080] As preferred, the nitrogen filling packaging adopts a multi-stage nitrogen filling packaging system, including the following steps:

[0081] (1) First-stage vacuum treatment, the vacuum degree is 50-100 Pa;

[0082] (2) Second-stage nitrogen filling, the nitrogen purity is greater than or equal to 99.999%;

[0083] (3) Third-stage nitrogen filling, the nitrogen filling pressure is 0.08-0.12 MPa;

[0084] (4) Heat sealing, the temperature is 130-150 DEG C, and the time is 0.8-1.2 seconds.

[0085] From the molecular level, the core of the application lies in the construction of a multi-level and multi-functional protection system. First, different animal sources are used as collagen, and a stable network structure is formed through intermolecular interaction. In this network structure, the side chain groups of different gelatin molecules (such as the epsilon-amino group of lysine and the carboxyl group of glutamic acid) interact through hydrogen bonds, ionic bonds and van der Waals forces to form a dense and flexible protective layer.

[0086] Secondly, the application of the compound enzyme preparation promotes the partial hydrolysis of gelatin molecules, producing more active groups. These active groups not only enhance the internal binding force of the gelatin network, but also provide more reaction sites for subsequent modification treatment. For example, papain may selectively cut specific peptide bonds in gelatin molecules, exposing more polar groups and increasing the interaction between gelatin and water molecules, thereby improving its solubility.

[0087] During the modification treatment stage, the addition of citric acid and lactic acid reacts with the amino groups in the gelatin molecules to form amide bonds, which not only enhances the acid stability of the small drop pills, but also improves their pH-sensitive release characteristics. The addition of sodium hyaluronate and chitosan further enhances the water retention and mechanical strength of the small drop pills. The carboxyl groups in sodium hyaluronate form ionic bonds with the amino groups in the gelatin molecules, while the amino groups of chitosan may react with the carboxyl groups in the gelatin molecules. This cross-linking action significantly improves the stability of the small drop pills.

[0088] In terms of preparation process, high-frequency pulse jet technology ensures the uniformity and integrity of each small drop pill by precisely controlling the droplet formation process. This technology not only improves the appearance quality of the product, but also improves the production efficiency of the small drop pill. Vacuum microwave drying technology maximizes the activity of DHA through a low-temperature, rapid dehydration process, while also improving the hardness uniformity of the small drop pill.

[0089] In summary, the present application constructs an efficient and stable DHA delivery system through multiple molecular level optimization and application of innovative processes. This system not only significantly improves the stability and bioavailability of DHA, but also optimizes the sensory quality and production efficiency of the product. These technical features of the present application have significant synergistic effects, which together achieve the overall improvement of DHA formulation performance, providing a new technical direction and application prospect for the field of functional foods and nutritional supplements.

[0090] Compared with the prior art, the DHA small drop pill and its preparation method can achieve the following beneficial effects:

[0091] The DHA small drop pill of the present application realizes excellent performance such as strong burst feeling, thin rubber, good solubility, heat resistance, non-oxidation and non-adhesion, while greatly improving the production efficiency and realizing the efficient preparation of second pill. These outstanding beneficial effects are due to the synergistic effect of the following key factors:

[0092] 1. Strong burst feeling: The present application uses multiple animal sources as collagen, combined with precise control of crosslinking degree, successfully constructs a small drop pill structure with both strength and elasticity. Experimental results show that the breaking force of the best embodiment 2 is as high as 895±30g, which is 37.7% higher than that of the traditional formula (comparative example 1). This enhanced mechanical strength ensures that the small drop pill can burst instantly in the oral cavity, releasing the internal DHA and providing excellent oral experience. The realization of this effect is mainly due to the synergistic effect of different animal sources as collagen, and the precise control of protein hydrolysis degree by complex enzyme preparation.

[0093] 2. Excellent solubility: By introducing hygroscopic materials such as sodium hyaluronate and chitosan, and using multiple modification processes, and through high-frequency pulse jet technology, the solubility of the small drop pills is significantly improved on a variety of gelatin combinations. The solubility test results show that the best embodiment 2 can be dissolved within 10 seconds, which is better than the control group. The thickness of the gelatin skin of the best embodiment 2 measured by the screw micrometer is only 0.06-0.1 mm. The thin and uniform gelatin skin also helps to improve the bursting sensation and solubility. This fast-dissolving property not only improves the taste, but also facilitates the rapid release and absorption of DHA. The improvement of solubility is mainly due to the synergistic effect between different animal sources as collagen, the uniform network structure achieved by modification technology, and the high-frequency pulse jet technology.

[0094] 3. Antioxidant properties: Stability test results show that even after 3 months of storage at high temperature of 40℃, the DHA of the best embodiment 2 has a higher retention rate, and the peroxide value and anisidine value are within the standard value, which is significantly different from the control group. To a certain extent, embodiment 2 can reduce the decomposition and oxidation of DHA at high temperature, and retain the content and flavor stability of DHA. The improvement of temperature resistance and antioxidant performance is mainly due to the synergistic effect between different animal sources as collagen, the use of complex enzyme preparation, and the modification process.

[0095] 4. Excellent anti-sticking performance: Stability test results show that even after 3 months of storage under high temperature and high humidity conditions of 40℃ and 75% RH, the best embodiment 2 still does not show obvious sticking phenomenon. This excellent anti-sticking performance not only improves the storage stability of the product, but also improves its taste and user experience. The improvement of anti-sticking performance is mainly due to the synergistic effect between different animal sources as collagen, the optimization of internal structure achieved by multiple modification processes, and the surface chemical modification brought by plasma treatment.

[0096] 5. Efficient second pill preparation: Production test data shows that the drop rate of the best embodiment can reach 15 pills per second. This efficient preparation of second pills greatly improves the production efficiency. The gelatin solution and the core liquid form a concentric flow column in the coaxial double-layer nozzle, the core liquid is in the inner layer, and the gelatin solution is in the outer layer. A number of synchronous pulse forces evenly distributed along the circumference of the concentric flow column are applied to the concentric flow column to cut it into a string of beads. This "one-piece pill" process also helps to maintain the activity of DHA and reduce the oxidative loss during production. The efficient preparation is mainly due to the precise control of the high-frequency pulse jet technology and the optimized rheological properties of gelatin.

[0097] In summary, the present application successfully realizes the comprehensive improvement of DHA small pellet in terms of bursting feeling, thin gelatin, solubility, oxidation resistance and preparation efficiency through multiple innovations and optimizations. The realization of these excellent performances not only results from the improvement of a single technology, but also the synergistic effect of multiple innovation points. Through the organic combination of material design, formula optimization and process innovation, the present application provides a new solution for the efficient use of DHA, which is expected to bring wide application in the field of functional food and nutritional supplements. DETAILED DESCRIPTION

[0098] To make the objectives, technical solutions and advantages of the present application clearer, the technical solutions of the present application will be described clearly and completely below in combination with specific embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0099] Embodiment 1

[0100] The present embodiment provides a DHA small pellet, which comprises a core liquid and a gelatin coating the core liquid. The core liquid is composed of 75 parts of DHA algal oil and 25 parts of sweet orange oil, and the gelatin is composed of 18 parts of gelatin, 12 parts of glycerol and 70 parts of water.

[0101] The preparation method of gelatin is as follows:

[0102] First, the raw materials are pretreated. 15 parts of pig bones, 15 parts of pig skins, 15 parts of cow bones, 15 parts of cow skins, 10 parts of fish skins and 10 parts of fish scales are respectively treated as follows:

[0103] Pig bones and cow bones: after cleaning and degreasing, they are crushed to 3-5 mm particles by a food-grade bone grinder, then soaked in a 0.8% food-grade citric acid solution for 7 hours, and finally washed with pure water until pH 6.8.

[0104] Pig skins and cow skins: after cleaning and degreasing, they are cut into small pieces of 1-2 cm, then soaked in a 0.3% food-grade sodium bicarbonate solution for 3.5 hours, and finally washed with pure water until pH 6.8.

[0105] Fish skins and fish scales: after cleaning and degreasing, they are treated with a 0.15% food-grade ascorbic acid solution for 2.5 hours, and then washed with pure water until pH 6.8.

[0106] Secondly, enzymatic pretreatment was performed. The pretreated raw materials were mixed, 6 times weight of pure water was added, and the pH was adjusted to 7.0. 0.2% of compound enzyme preparation (collagenase 45%, papain 35%, neutral protease 15%, alkaline protease 5%) was added, and enzymolysis was carried out at 45°C for 3.2 hours, stirring for 2.5 minutes every 30 minutes, wherein the activity of collagenase was 220000 U / g; the activity of papain was 650000 U / g, 30-40%; the activity of neutral protease was 110000 U / g; and the activity of alkaline protease was 220000 U / g.

[0107] Then, enzyme inactivation was performed. The pH was adjusted to 7.5, and the temperature was quickly raised to 63°C using a plate heat exchanger and maintained for 13 minutes.

[0108] Next, gelatin extraction was performed. The enzymolysis mixture was extracted in a multi-stage extraction tank for 2.2 hours: first stage 65°C, 35 minutes; second stage 69°C, 45 minutes; and third stage 73°C, 55 minutes. After each stage of extraction, ultrasonic treatment was performed for 5 minutes (22 kHz, 350 W).

[0109] Separation and purification were performed using two-step centrifugation and one-step membrane filtration: primary centrifugation at 5200 rpm for 25 minutes; cross-flow filtration using a ceramic membrane with a 100 kDa molecular weight cut-off, with a transmembrane pressure difference of 0.15 MPa; and secondary centrifugation at 6200 rpm for 20 minutes.

[0110] The gelatin solution was concentrated to a concentration of 20% using a two-stage ultrafiltration system: first stage using a polyether sulfone membrane with a 15 kDa molecular weight cut-off, with an operating pressure of 0.35 MPa; and second stage using a polyvinylidene fluoride membrane with a 5 kDa molecular weight cut-off, with an operating pressure of 0.45 MPa.

[0111] Modification treatment was performed: 0.4% citric acid and 0.1% lactic acid were added to the concentrated solution and stirred evenly; 0.2% sodium hyaluronate (20 kDa) and 0.1% chitosan (75 kDa) were added, stirred for 20 minutes, and stirred for 10 minutes; and finally the pH was adjusted to 6.9.

[0112] Powder was prepared using low-temperature vacuum spray drying technology, with an inlet temperature of 76°C, an outlet temperature of 50°C, an atomization pressure of 0.24 MPa, a vacuum degree of 70 Pa, and food-grade nitrogen used as the drying medium.

[0113] Finally, a low-temperature airflow pulverizer was used (feed temperature 12°C) for pulverization, a 100-mesh stainless steel screen was used, and a food-grade electrostatic dust collector was used for dust removal. Near-infrared spectroscopy was used to detect the purity of the gelatin, ensuring that the purity reached 98.5%.

[0114] Next, the modification treatment is carried out: 0.4% citric acid and 0.1% lactic acid are added to the concentrated solution, and stirred uniformly; 0.2% sodium hyaluronate and 0.1% chitosan are added, stirred for 20 minutes, and stirred for 10 minutes; finally, the pH is adjusted to 6.9.

[0115] The preparation method of the DHA small pellet pill comprises the following steps:

[0116] (1) Preparation of core liquid: uniformly mix DHA algal oil and sweet orange oil for 30 minutes to obtain a uniform core liquid.

[0117] (2) Preparation of gelatin solution: pour water into the gelatinizing pot, heat to 70°C, add gelatin and glycerol, stir until the gelatin is completely dissolved, and the gelatin solution is clear and transparent, vacuum degassing at 80°C for 8 minutes.

[0118] (3) Dropping by high-frequency pulse jet technology: the gelatin solution and the core liquid form a concentric flow column in the coaxial double-layer nozzle, the core liquid is in the inner layer, and the gelatin solution is in the outer layer. A number of synchronous pulse forces uniformly distributed along the circumference of the concentric flow column are applied to the concentric flow column to cut it into a string of beads. The gelatin solution temperature is 80°C, the flow rate is 6.0 mL / min; the core liquid temperature is 45°C, the flow rate is 3.0 mL / min; the nozzle vibration frequency is 150 Hz, the nozzle aperture is 0.3 mm, and the dropping height is 20 cm.

[0119] (4) Immersing the dropped pellets in capric acid glycerol, and cold setting at 5°C for 4h

[0120] (5) Separation by low-temperature centrifugation technology: centrifugation at 1500 rpm for 5 minutes at 5°C.

[0121] (6) Vacuum microwave drying: microwave power 200W, vacuum degree 50Pa, drying time 15 minutes, intermittent mode 10 seconds on and 5 seconds off, control the final water content of the product to be 2%.

[0122] (7) Surface treatment by low-temperature plasma technology: place the dried small pellets in a low-temperature plasma treatment device, use argon as the working gas, gas flow 20sccm, radio frequency power 50W, treatment pressure 10Pa, treatment time 30 seconds, and treatment temperature control at 35°C.

[0123] (8) Screening: use ultrasonic vibration screening machine, screen mesh aperture 6.2mm, vibration frequency 50Hz, screening time 2 minutes.

[0124] (9) Nitrogen filling packaging: use multi-stage nitrogen filling packaging system, first stage vacuum degree 50Pa, second stage nitrogen purity 99.999%, third stage nitrogen filling pressure 0.08MPa, heat sealing temperature 130°C, time 0.8 seconds.

[0125] In this embodiment, the combination of DHA algal oil and sweet orange oil not only provides a high content of DHA, but also imparts a good flavor to the product. The multiple modification of gelatin significantly improves the strength and elasticity of the gelatin skin, while improving its solubility. The high-frequency pulse jet technology and rapid condensation ensure the uniformity and burst feeling of the small droplet pills. The multi-stage nitrogen filling packaging system effectively prolongs the shelf life of the product.

[0126] Example 2

[0127] In the DHA small droplet pills provided in this embodiment, the core liquid is composed of 85 parts of DHA algal oil and 15 parts of sweet orange oil, and the gelatin skin is composed of 22 parts of gelatin, 8 parts of glycerol and 70 parts of water.

[0128] The preparation method of gelatin is as follows:

[0129] (1) Pretreatment of raw materials:

[0130] a) After washing and degreasing 25 parts of pig bones and 25 parts of cow bones, they are crushed to 3 mm particles with a food-grade bone grinder, soaked in 1% food-grade citric acid solution for 8 hours, and then washed with pure water until pH 7.0;

[0131] b) After washing and degreasing 25 parts of pig skin and 25 parts of cow skin, they are cut into 1 cm pieces, soaked in 0.4% food-grade sodium bicarbonate solution for 4 hours, and then washed with pure water until pH 7.0;

[0132] c) After washing and degreasing 20 parts of fish skin and 20 parts of fish scales, they are treated with 0.2% food-grade ascorbic acid solution for 3 hours, and then washed with pure water until pH 7.0;

[0133] (2) Enzymatic pretreatment:

[0134] Mix the pretreated raw materials according to the ratio, add 6 times the weight of pure water, and adjust the pH to 7.2;

[0135] Add 0.3% of a composite enzyme preparation, which has the following composition:

[0136] Collagenase (activity 200000 U / g): 40%;

[0137] Papain (activity 600000 U / g): 30%;

[0138] Neutral protease (activity 100000 U / g): 20%;

[0139] Alkaline protease (activity 200000 U / g): 10%;

[0140] Enzyme hydrolysis at 47°C for 3.5 hours, stirring every 30 minutes for 3 minutes;

[0141] (3) Enzyme inactivation:

[0142] Adjust pH to 7.8, use plate heat exchanger to quickly raise temperature to 64℃ and keep for 15 minutes, ensure complete enzyme inactivation;

[0143] (4) Gelatin extraction:

[0144] Transfer the enzyme-degraded mixture to a multi-stage extraction tank with temperature gradient, total extraction time 2.5 hours:

[0145] a) First stage: 66℃, 40 minutes

[0146] b) Second stage: 70℃, 50 minutes

[0147] c) Third stage: 74℃, 60 minutes

[0148] After the end of each stage of extraction, low-frequency ultrasonic treatment (frequency 25 kHz, power 400W) for 5 minutes;

[0149] (5) Separation and purification:

[0150] Use a combined separation technology of two-step centrifugation and one-step membrane filtration:

[0151] a) Primary centrifugation: 5500 rpm, 25 minutes

[0152] b) Fine filtration: use ceramic membrane with 100 kDa cut-off molecular weight for cross-flow filtration, transmembrane pressure difference 0.2 MPa

[0153] c) Secondary centrifugation: 6500 rpm, 20 minutes;

[0154] (6) Concentration:

[0155] Use a two-stage ultrafiltration system to concentrate the gelatin solution:

[0156] a) First stage: use polyether sulfone membrane with 15 kDa cut-off molecular weight, operating pressure 0.4 MPa

[0157] b) Second stage: use polyvinylidene fluoride membrane with 5 kDa cut-off molecular weight, operating pressure 0.5 MPa

[0158] Control the final gelatin solution concentration to be 22%;

[0159] (7) Modification treatment:

[0160] Add 0.8% citric acid and 0.3% lactic acid to the concentrated solution and stir evenly; add 0.4% sodium hyaluronate and 0.3% chitosan and stir for 25 minutes; finally adjust pH to 7.3;

[0161] (8) Drying:

[0162] Low-temperature vacuum spray drying technology was used:

[0163] a) Inlet temperature: 78°C;

[0164] b) Outlet temperature: 52°C;

[0165] c) Atomization pressure: 0.26 MPa;

[0166] d) Vacuum degree: 80 Pa;

[0167] e) Drying medium: food-grade nitrogen;

[0168] (9) Crushing and sieving:

[0169] a) Crushed using a low-temperature airflow crusher, with the feed temperature controlled at 15°C;

[0170] b) Passed through a 100-mesh stainless steel screen;

[0171] c) Dust removal treatment was performed using a food-grade electrostatic precipitator;

[0172] d) Near-infrared spectroscopy was used to detect the purity of the gelatin, ensuring a purity of ≥99%;

[0173] The preparation method of DHA microdroplet pills includes the following steps:

[0174] (1) Prepare the core liquid: Mix DHA algal oil and sweet orange oil evenly for 30 minutes to obtain a uniform core liquid.

[0175] (2) Prepare the gelatin solution: Pour water into the gelatinizing tank and heat to 75°C. Add gelatin and glycerol and stir until the gelatin is completely dissolved. The gelatin solution is clear and transparent. Vacuum degassing is performed at 85°C for 12 minutes.

[0176] (3) Use high-frequency pulse jet technology for droplet preparation: The gelatin solution and the core liquid form a concentric flow column in the coaxial double-layer nozzle. The core liquid is in the inner layer and the gelatin solution is in the outer layer. A number of synchronous pulse forces evenly distributed along the circumference of the concentric flow column are applied to the concentric flow column to cut it into a string of beads. The gelatin solution temperature is 85°C, the flow rate is 8.0 mL / min; the core liquid temperature is 50°C, the flow rate is 4.0 mL / min; the nozzle vibration frequency is 200 Hz, the nozzle aperture is 0.5 mm, and the droplet preparation height is 30 cm.

[0177] (4) Immerse the prepared pills in capric and caprylic acid glycerides and store them at 5°C for 4 hours for shaping.

[0178] (5) Use low-temperature centrifugation technology for separation: centrifuge at 2000 rpm for 8 minutes at 8°C.

[0179] (6) Vacuum microwave drying: microwave power 300W, vacuum degree 100Pa, drying time 20 minutes, intermittent mode 10 seconds on and 5 seconds off, control the final moisture content of the product at 2%.

[0180] (7) Surface treatment using low-temperature plasma technology: place the dried small pellets in a low-temperature plasma treatment device, use argon as the working gas, gas flow 30sccm, radio frequency power 100W, treatment pressure 50Pa, treatment time 20, treatment temperature controlled at 25℃.

[0181] (8) Screening: use an ultrasonic-assisted vibration screening machine, screen mesh aperture 5.8mm, screening time 3 minutes.

[0182] (9) Nitrogen filling packaging: use a multi-stage nitrogen filling packaging system, first stage vacuum degree 100Pa, second stage nitrogen purity 99.999%, third stage nitrogen filling pressure 0.12MPa, heat sealing temperature 150℃, time 1.2 seconds.

[0183] In this embodiment, a higher proportion of DHA algal oil provides a higher DHA content, and the increase of fish gelatin in the gelatin improves the low-temperature solubility of the gelatin skin. Higher enzyme hydrolysis temperature and time improve the extraction efficiency of gelatin.

[0184] Example 3

[0185] The DHA small pellets provided in this embodiment are composed of 80 parts of DHA algal oil and 20 parts of sweet orange oil as the core liquid, and 20 parts of gelatin, 10 parts of glycerol and 70 parts of water as the gelatin skin.

[0186] The preparation method of gelatin is as follows: (1) raw material pretreatment:

[0187] a) After cleaning and degreasing 20 parts of pig bones and 20 parts of beef bones, they are crushed to 4mm particles with a food-grade bone grinder, then soaked in 0.75% food-grade citric acid solution for 7 hours, and then washed with pure water until pH 6.8;

[0188] b) After cleaning and degreasing 20 parts of pig skin and 20 parts of beef skin, they are cut into 1.5cm small pieces, then soaked in 0.3% food-grade sodium bicarbonate solution for 3.5 hours, and then washed with pure water until pH 6.8;

[0189] c) After cleaning and degreasing 15 parts of fish skin and 15 parts of fish scales, they are treated with 0.15% food-grade ascorbic acid solution for 2.5 hours, and then washed with pure water until pH 6.8;

[0190] (2) Enzymatic pretreatment:

[0191] The pretreated raw materials were mixed according to the ratio, 6 times the weight of pure water was added, and the pH was adjusted to 7.0;

[0192] 0.22% of a composite enzyme preparation was added, which consisted of:

[0193] Collagenase (activity 200000 U / g): 45%;

[0194] Papain (activity 600000 U / g): 35%;

[0195] Neutral protease (activity 100000 U / g): 15%;

[0196] Alkaline protease (activity 200000 U / g): 5%;

[0197] Enzymatic hydrolysis at 45°C for 3.2 hours, with stirring every 30 minutes for 2.5 minutes;

[0198] (3) Enzyme inactivation:

[0199] The pH was adjusted to 7.6, and the temperature was quickly raised to 63°C using a plate heat exchanger and maintained for 13 minutes to ensure complete enzyme inactivation;

[0200] (4) Gelatin extraction:

[0201] The enzymatically hydrolyzed mixture was transferred to a multi-stage extraction tank with a temperature gradient, with a total extraction time of 2.2 hours:

[0202] a) First stage: 65°C, 35 minutes;

[0203] b) Second stage: 69°C, 45 minutes;

[0204] c) Third stage: 73°C, 55 minutes;

[0205] After each stage of extraction, low-frequency ultrasonic treatment was performed for 5 minutes (frequency 22 kHz, power 350W);

[0206] (5) Separation and purification:

[0207] A combined separation technique of two-step centrifugation and one-step membrane filtration was used:

[0208] a) Primary centrifugation: 5200 rpm, 25 minutes;

[0209] b) Fine filtration: cross-flow filtration using a ceramic membrane with a molecular weight cut-off of 100 kDa, transmembrane pressure difference 0.15 MPa

[0210] c) Secondary centrifugation: 6200 rpm, 20 minutes;

[0211] (6) Concentration:

[0212] The gelatin solution was concentrated using a two-stage ultrafiltration system:

[0213] a) First stage: polyether sulfone membrane with a 15 kDa molecular weight cut-off, operating pressure 0.35 MPa;

[0214] b) Second stage: polyvinylidene fluoride membrane with a 5 kDa molecular weight cut-off, operating pressure 0.45 MPa;

[0215] The final gelatin solution concentration was controlled at 20%;

[0216] (7) Modification:

[0217] 0.6% citric acid and 0.2% lactic acid were added to the concentrated solution and stirred evenly; 0.3% sodium hyaluronate and 0.2% chitosan were added and stirred for 22 minutes; stirred for 10 minutes; finally adjust the pH to 7.1;

[0218] (8) Drying:

[0219] Low-temperature vacuum spray drying technology was used:

[0220] a) Inlet temperature: 76°C;

[0221] b) Outlet temperature: 50°C;

[0222] c) Atomization pressure: 0.24 MPa;

[0223] d) Vacuum degree: 70 Pa;

[0224] e) Drying medium: food-grade nitrogen;

[0225] (9) Crushing and sieving:

[0226] a) Crushed using a low-temperature jet mill, with the feed temperature controlled at 12°C;

[0227] b) Passed through a 100-mesh stainless steel screen;

[0228] c) Dust removal treatment was performed using a food-grade electrostatic precipitator;

[0229] d) Near-infrared spectroscopy was used to detect the purity of the gelatin, ensuring a purity of ≥98.5%.

[0230] The preparation method of the DHA micro-droplet pills includes the following steps:

[0231] (1) Preparation of core liquid: mix DHA algal oil and sweet orange oil evenly for 30 minutes to obtain a uniform core liquid.

[0232] (2) Preparation of gelatin solution: pour water into the gelatinizing tank, heat to 73°C, add gelatin and glycerol, stir until the gelatin is completely dissolved, and the gelatin solution is clear and transparent. Vacuum degassing at 83°C for 10 minutes.

[0233] (3) Dropping using high-frequency pulse jet technology: the gelatin solution and the core liquid form a concentric flow column in the coaxial double-layer nozzle, with the gelatin solution in the outer layer. A number of synchronous pulse forces evenly distributed along the circumference of the concentric flow column are applied to the concentric flow column to cut it into a string of beads. The gelatin solution temperature is 83°C, and the flow rate is 7.0 mL / min; the core liquid temperature is 48°C, and the flow rate is 3.5 mL / min; the nozzle vibration frequency is 175 Hz, the nozzle aperture is 0.4 mm, and the dropping height is 25 cm.

[0234] (4) Immersing the dropped pellets in capric and caprylic acid glycerides, and setting at 5°C for 4 hours.

[0235] (5) Separation using low-temperature centrifugation technology: centrifugation at 8°C and 1750 rpm for 7 minutes.

[0236] (6) Vacuum microwave drying: microwave power 250 W, vacuum degree 75 Pa, drying time 18 minutes, intermittent mode 10 seconds on and 5 seconds off, and the final water content of the product is controlled at 2%.

[0237] (7) Surface treatment using low-temperature plasma technology: treatment time 25 seconds.

[0238] (8) Screening: using an ultrasonic-assisted vibrating screening machine, screen aperture 6.0 mm, and screening time 2.5 minutes.

[0239] (9) Nitrogen-filled packaging: using a multi-stage nitrogen-filled packaging system, first-stage vacuum degree 75 Pa, second-stage nitrogen purity 99.999%, third-stage nitrogen filling pressure 0.1 MPa, heat sealing temperature 140°C, and time 1 second.

[0240] In this embodiment, the ratio of DHA algal oil and sweet orange oil reaches a good balance, ensuring sufficient DHA content and maintaining appropriate flavor. The balanced ratio of various gelatins in the gelatin provides comprehensive performance advantages. Moderate modification treatment and appropriate process parameters make the product reach a good balance in various aspects of performance.

[0241] Example 4

[0242] In the DHA small pellet provided in this embodiment, the core liquid is composed of 78 parts of DHA algal oil and 22 parts of sweet orange oil, and the gelatin is composed of 19 parts of gelatin, 9 parts of glycerol, and 72 parts of water.

[0243] The preparation method of gelatin is as follows:

[0244] a) 15 parts of pig bone, 15 parts of beef bone were cleaned and defatted, then ground into 5mm particles by a food-grade bone grinder, soaked in 0.5% food-grade citric acid solution for 6 hours, and then washed with pure water until pH 6.5;

[0245] b) 15 parts of pig skin, 15 parts of beef skin were cleaned and defatted, then cut into 2cm pieces, soaked in 0.2% food-grade sodium bicarbonate solution for 3 hours, and then washed with pure water until pH 6.5;

[0246] c) 10 parts of fish skin, 10 parts of fish scales were cleaned and defatted, then treated with 0.1% food-grade ascorbic acid solution for 2 hours, and then washed with pure water until pH 6.5;

[0247] (2) Enzymatic pretreatment:

[0248] The pretreated various raw materials were mixed according to the ratio, 6 times the weight of pure water was added, and the pH was adjusted to 6.8;

[0249] 0.15% of a composite enzyme preparation was added, which consisted of:

[0250] Collagenase (activity 200000 U / g): 40%;

[0251] Papain (activity 600000 U / g): 30%;

[0252] Neutral protease (activity 100000 U / g): 20%;

[0253] Alkaline protease (activity 200000 U / g): 10%;

[0254] Enzymatic hydrolysis at 42°C for 3 hours, stirring every 30 minutes for 2 minutes;

[0255] (3) Enzyme inactivation:

[0256] Adjusting the pH to 7.4, using a plate heat exchanger to quickly raise the temperature to 62°C and maintain for 12 minutes to ensure complete enzyme inactivation;

[0257] (4) Gelatin extraction:

[0258] The enzymatically hydrolyzed mixture was transferred to a multi-stage extraction tank with a temperature gradient, with a total extraction time of 2 hours:

[0259] a) First stage: 64°C, 30 minutes

[0260] b) Second stage: 68°C, 40 minutes

[0261] c) Third stage: 72°C, 50 minutes

[0262] After each extraction step, a 5 minutes low frequency sonication (frequency 20 kHz, power 300 W) was performed;

[0263] (5) Isolation and purification:

[0264] A combined separation technique of two-step centrifugation and one-step membrane filtration was used:

[0265] a) Primary centrifugation: 5000 rpm, 25 minutes

[0266] b) Fine filtration: cross-flow filtration using ceramic membrane with a cut-off molecular weight of 100 kDa, transmembrane pressure difference 0.1 MPa

[0267] c) Secondary centrifugation: 6000 rpm, 20 minutes

[0268] (6) Concentration:

[0269] A two-stage ultrafiltration system was used to concentrate the gelatin solution:

[0270] a) First stage: polyether sulfone membrane with a cut-off molecular weight of 15 kDa, operating pressure 0.3 MPa

[0271] b) Second stage: polyvinylidene fluoride membrane with a cut-off molecular weight of 5 kDa, operating pressure 0.4 MPa

[0272] The final gelatin solution concentration was controlled at 18%;

[0273] (7) Modification:

[0274] 0.7% citric acid and 0.25% lactic acid were added to the concentrated solution and stirred evenly; 0.35% sodium hyaluronate and 0.25% chitosan were added and stirred for 23 minutes; stirred for 10 minutes; finally, the pH was adjusted to 7.2;

[0275] (8) Drying:

[0276] Low-temperature vacuum spray drying technology was used:

[0277] a) Inlet temperature: 75°C;

[0278] b) Outlet temperature: 48°C;

[0279] c) Atomization pressure: 0.22 MPa;

[0280] d) Vacuum degree: 60 Pa;

[0281] e) Drying medium: food-grade nitrogen;

[0282] (9) Crushing and sieving:

[0283] a) Pulverization using a cryogenic airflow mill, with the feed temperature controlled at 10°C;

[0284] b) Passing through a 100-mesh stainless steel screen;

[0285] c) Dust removal treatment using a food-grade electrostatic precipitator;

[0286] d) Using near-infrared spectroscopy to detect the purity of gelatin, ensuring a purity of ≥98%;

[0287] The preparation method of DHA small pellets includes the following steps:

[0288] (1) Prepare the core liquid: Mix DHA algal oil and sweet orange oil evenly.

[0289] (2) Prepare the gelatin solution: Pour water into the gelatinizing pot and heat to 72°C. Add gelatin and glycerol, stir until the gelatin is completely dissolved, and the gelatin solution is clear and transparent. Vacuum degassing at 82°C for 11 minutes.

[0290] (3) Use high-frequency pulse jet technology for dripping: The gelatin solution and the core liquid form a concentric flow column in the coaxial double-layer nozzle. The gelatin solution is in the outer layer, and a number of synchronous pulse forces evenly distributed along the circumference of the concentric flow column are applied to the concentric flow column, cutting the concentric flow column into a string of beads. The gelatin solution temperature is 82°C, the flow rate is 7.5 mL / min; the core liquid temperature is 47°C, the flow rate is 3.8 mL / min; the nozzle vibration frequency is 185 Hz, the nozzle aperture is 0.45 mm, and the dripping height is 28 cm.

[0291] (4) Immersing the dripped pellets in capric and caprylic acid glycerides, and setting at 5°C for 4 hours.

[0292] (5) Use low-temperature centrifugation technology for separation: centrifuge at 1800 rpm for 6 minutes at 8°C.

[0293] (6) Use vacuum microwave drying: microwave power 275W, vacuum degree 85Pa, drying time 17 minutes, intermittent mode 10 seconds on and 5 seconds off, control the final water content of the product to be 2%.

[0294] (7) Use low-temperature plasma technology for surface treatment: Place the dried small pellets in a low-temperature plasma treatment device, use argon as the working gas, gas flow 28sccm, radio frequency power 80W, treatment pressure 35Pa, treatment time 27 seconds, treatment temperature controlled at 28°C.

[0295] (8) Screening: Use an ultrasonic-assisted vibrating screening machine, screen aperture 6.1mm, screening time 2.8 minutes.

[0296] (9) Nitrogen filling packaging: A multi-stage nitrogen filling packaging system was used, with a first-stage vacuum degree of 85 Pa, a second-stage nitrogen purity of 99.999%, a third-stage nitrogen filling pressure of 0.11 MPa, a heat sealing temperature of 145°C, and a time of 1.1 seconds.

[0297] In this embodiment, the ratio of DHA algal oil and sweet orange oil optimizes the nutritional value and sensory experience of the product. The moderate increase in fish gelatin in the gelatin improves the low-temperature solubility of the gelatin skin while maintaining the excellent gel properties of pig and cow-derived gelatin. Fine-tuned enzymatic conditions and modification parameters enable the final product to achieve a good balance in strength, elasticity, and solubility.

[0298] It is worth noting that all raw materials and processes used in all examples strictly comply with food safety standards, ensuring the safety of the final product. At the same time, through multiple modifications and innovative processes such as the use of composite enzyme preparations, multi-stage ultrafiltration systems, high-frequency pulse jet technology, and multi-stage nitrogen filling packaging systems, the quality and stability of the product are effectively improved, providing consumers with high-quality DHA supplement options.

[0299] Comparative Example 1: DHA small drop pills with single-source gelatin

[0300] This comparative example aims to verify the superiority of using multiple animal sources as collagen composite, compared with Example 1.

[0301] In the DHA small drop pills provided by this comparative example, the core liquid composition is the same as Example 1, and the gelatin skin is composed of 18 parts of single pig skin source, 12 parts of glycerol, and 70 parts of water.

[0302] The preparation method of gelatin is basically the same as Example 1.

[0303] The preparation method of DHA small drop pills is basically the same as Example 1.

[0304] Result analysis: Compared with Example 1, the small drop pills prepared in this comparative example perform poorly in mechanical strength, solubility, antioxidant properties, and heat resistance. This confirms the importance of using multiple sources of gelatin in combination, as different sources of gelatin can complement each other and provide more comprehensive performance.

[0305] Comparative Example 2: DHA small drop pills with non-composite enzyme preparation

[0306] This comparative example aims to verify the necessity of using composite enzyme preparations, compared with Example 1.

[0307] The formulation of this comparative example is the same as Example 1, but only neutral protease is added when preparing gelatin. Other preparation steps remain unchanged.

[0308] Result Analysis: Compared with Example 1, the gelatin-coated strength of the mini-pill obtained in this comparative example is lower, and there is a certain degree of turbidity, and the antioxidant property also decreases. This indicates that the use of complex enzyme preparation helps to improve the extraction efficiency and purity of gelatin, thereby improving the quality of the final product.

[0309] Comparative Example 3: DHA mini-pill without modification treatment

[0310] This comparative example aims to verify the influence of modification treatment on product performance, compared with Example 1.

[0311] The formulation of this comparative example is the same as Example 1, but when preparing gelatin, all modification treatment steps (including adding citric acid, lactic acid, sodium hyaluronate, chitosan) are omitted. Other preparation steps remain unchanged.

[0312] Result Analysis: Compared with Example 1, the mini-pill obtained in this comparative example performs poorly in heat resistance, moisture resistance, and storage stability. This confirms the important role of modification treatment in improving the overall performance of the product, especially in improving the functional properties of the gelatin coating and extending the shelf life of the product.

[0313] Comparative Example 4: DHA mini-pill using traditional dripping technology

[0314] This comparative example aims to verify the superiority of high-frequency pulse jet technology, compared with Example 1.

[0315] The formulation of this comparative example is the same as Example 1, but during the mini-pill forming stage, traditional gravity dripping technology is used instead of high-frequency pulse jet technology. The specific operation is as follows:

[0316] Heat the gelatin coating liquid to 82°C and the core liquid to 47°C. Use a dripping device with coaxial double tubes to form droplets under the action of gravity. The droplets are directly dropped into oil at 10°C for cooling and forming. Other preparation steps are the same as Example 1.

[0317] Result Analysis: Compared with Example 1, the mini-pill obtained in this comparative example has uneven particle size distribution, irregular shape, and a certain proportion of broken particles. This shows that high-frequency pulse jet technology can significantly improve the uniformity and forming quality of mini-pill, which is beneficial to improving the appearance quality and internal structure consistency of the product.

[0318] Comparative Example 5: DHA mini-pill using conventional drying method

[0319] This comparative example aims to verify the superiority of vacuum microwave drying technology, compared with Example 1.

[0320] The formulation of this comparative example is the same as Example 1, but during the drying stage, traditional drying methods are used instead of vacuum microwave drying. The specific operation is as follows:

[0321] The droplet pills were placed in a rotating cage at 25°C, and the drying time was 6 hours. The other preparation steps were the same as in Example 2.

[0322] Result analysis: Compared with Example 1, the hardness of the droplet pills prepared in this comparative example varied greatly. This indicates that the vacuum microwave drying technology can avoid uneven drying, shorten the drying time, and improve the quality of the product.

[0323] Comparative Example 6: DHA droplet pills without surface treatment

[0324] This comparative example aims to verify the necessity of low-temperature plasma surface treatment technology, compared with Example 1.

[0325] The formulation of this comparative example is the same as Example 1, but the low-temperature plasma surface treatment step is omitted. The other preparation steps remain unchanged.

[0326] Result analysis: Compared with Example 1, the droplet pills prepared in this comparative example are more prone to sticking in a high-humidity environment. This confirms the important role of low-temperature plasma surface treatment technology in improving the moisture resistance of the product.

[0327] Through these six comparative examples, it can be clearly seen that the present invention has innovative points and superiorities in multiple aspects. The application of multiple animal-derived collagen, complex enzyme preparation, multiple modification processes, high-frequency pulse jet technology, vacuum microwave drying, and low-temperature plasma surface treatment, etc. innovative points, together form a synergistically optimized system. This synergistic effect not only improves the quality and stability of DHA droplet pills, but also significantly improves their processing performance and user experience.

[0328] It is particularly noteworthy that there is a close relationship between these innovative points. For example, the combined use of multiple animal-derived gelatin raw materials provides more optimization space for subsequent modification processes, while the application of complex enzyme preparation lays the foundation for the preparation of high-quality gelatin. The high-frequency pulse jet technology combined with the excellent performance of modified gelatin realizes the efficient and uniform formation of droplet pills. Vacuum microwave drying and low-temperature plasma surface treatment further improve the stability and sensory quality of the product.

[0329] This all-around technical innovation and optimization makes the DHA droplet pills of the present invention reach a new height in terms of nutritional value, stability, processing performance, and user experience, fully embodying the creativity and industrial application potential of the present invention.

[0330] In order to comprehensively evaluate the effectiveness and superiority of the present invention, a series of professional test experiments are designed to verify the effectiveness and superiority of the present invention.

[0331] Experiment 1: Droplet pill strength test

[0332] Objective of the experiment: To evaluate the effect of different formulations and preparation methods on the strength of DHA Droplet Pellets.

[0333] Experimental method:

[0334] 1. TA.XTplus texture analyzer was used to determine the breaking force of the Droplet Pellets.

[0335] 2. Test conditions: compression speed 1 mm / s, compression depth 50% of the diameter of the Droplet Pellets.

[0336] 3. 30 pellets were tested for each sample, and the average value was taken.

[0337] Experiment II: Solubility evaluation experiment

[0338] Objective of the experiment: To evaluate the effect of different formulations and preparation methods on the solubility of DHA Droplet Pellets.

[0339] Experimental method:

[0340] 1. Instrumentation: A rising and falling disintegration apparatus was used, which consisted of a metal support that could be raised and lowered, a basket with a screen at the lower end, and a baffle. The basket was suspended on the support by a stainless steel shaft at the upper end, and was immersed in a 1000 ml beaker. The position of the basket was adjusted so that when it was lowered to the lowest point, the screen was 25 mm from the bottom of the beaker, and the beaker contained water at a temperature of 37°C ± 1°C. The water level was adjusted so that when the basket was raised to the highest point, the screen was 15 mm below the water surface.

[0341] 2. Six Droplet Pellets were placed in the glass tube of the basket described above.

[0342] 3. The disintegration apparatus was started and the test was conducted.

[0343] 4. The dissolution of the rubber was observed.

[0344] Experiment III: Stability test

[0345] Objective of the experiment: To evaluate the effect of different formulations and preparation methods on the storage stability of DHA Droplet Pellets.

[0346] Experimental method:

[0347] 1. The Droplet Pellet samples were stored at 40°C and 75% RH.

[0348] 2. The samples were taken for testing at 3 months.

[0349] 3. The high temperature test items included flavor, appearance (adhesion), DHA content, peroxide value, and anisidine value, and the high humidity test items included appearance (adhesion).

[0350] Experiment IV: In vitro digestion simulation experiment

[0351] Experimental purpose: to evaluate the release characteristics of DHA small pellets in simulated digestion process.

[0352] Experimental method:

[0353] 1. Simulate the oral, gastric and small intestinal digestion process in turn.

[0354] 2. Oral stage: 37℃, pH 6.8, 10 minutes.

[0355] 3. Gastric stage: 37℃, pH 2.0, 2 hours.

[0356] 4. Small intestinal stage: 37℃, pH 7.4, 2 hours.

[0357] 5. Sample at the end of each stage, and determine the DHA content using HPLC.

[0358] The experimental results are as follows:

[0359] Table 1: Results of breaking strength and solubility test

[0360] Sample Appearance Force to break (g) Dissolution time (sec) Example 1 Gelatin skin transparent, visible contents clear, pellet size uniform 820±25 20±1 Example 2 Gelatin skin transparent, visible contents clear, pellet size uniform 895±30 10±1 Example 3 Gelatin skin transparent, visible contents clear, pellet size uniform 855±28 13±1 Example 4 Gelatin skin transparent, visible contents clear, pellet size uniform 870±27 16±1 Comparative Example 1 Gelatin skin transparent, visible contents clear, pellet size uniform 650±35 60±1 Comparative Example 2 Gelatin skin transparency poor, contents 690±33 25±1 Comparative Example 3 Gelatin skin transparent, visible contents clear, pellet size uniform 760±32 40±1 Comparative Example 4 Gelatin skin transparent, visible contents clear, pellet size uniform 800±29 28±1 Comparative Example 5 Gelatin skin transparent, visible contents clear, pellet size uniform 810±60 25±1 Comparative Example 6 Gelatin skin transparent, visible contents clear, pellet size uniform 820±28 20±1

[0361] Note: The breaking strength is positively correlated with the bursting sensation of being squeezed in the mouth.

[0362] Table 2: Results of 3-month stability test under 40℃ conditions

[0363] Sample Flavor Sticking DHA content retention (%) Peroxide value (mmol / kg) Anisidine value Example 1 Sweet orange flavor, no off-flavor No sticking 95.2±1.5 5.8±0.2 9.2±0.2 Example 2 Sweet orange flavor, no off-flavor No sticking 96.8±1.2 2.3±0.1 6.8±0.2 Example 3 Sweet orange flavor, no off-flavor No sticking 96.0±1.3 4.5±0.2 8.5±0.2 Example 4 Sweet orange flavor, no off-flavor No sticking 96.5±1.4 4.4±0.1 8.7±0.2 Comparative Example 1 Strong fishy and rancid odor Severe sticking 80.5±2.0 17.7±0.2 25.7±0.4 Comparative Example 2 Strong fishy and rancid odor Mild sticking 87.2±1.8 12.8±0.3 17.6±0.2 Comparative Example 3 Strong fishy and rancid odor Severe sticking 84.7±1.9 14.2±0.3 23.4±0.3 Comparative Example 4 Mild fishy and rancid odor No sticking 93.8±1.6 8.5±0.2 13.2±0.2 Comparative Example 5 Mild fishy and rancid odor Mild sticking 92.5±1.7 9.2±0.3 12.5±0.2 Comparative Example 6 Mild fishy and rancid odor Severe sticking 94.3±1.5 8.1±0.2 14.1±0.2

[0364] It is noted that the lower the peroxide value and anisidine value, the lower the degree of oxidation of the algal oil, and the standard is: anisidine value ≤ 15, peroxide value ≤ 7.5 mmol / kg.

[0365] Table 3: Results of 3-month stability test under 75% RH conditions

[0366] Sample Sticking Example 1 No sticking Example 2 No sticking Example 3 No sticking Example 4 No sticking Comparative Example 1 Severe sticking Comparative Example 2 Mild sticking Comparative Example 3 Severe sticking Comparative Example 4 No sticking Comparative Example 5 Mild sticking Comparative Example 6 Severe sticking

[0367] Table 4: Results of in vitro digestion simulation experiment

[0368] Sample DHA release rate (%) in small intestine stage Example 1 92.8±1.7 Example 2 95.2±1.5 Example 3 93.9±1.6 Example 4 94.5±1.6 Comparative Example 1 83.7±2.3 Comparative Example 2 87.4±2.1 Comparative Example 3 85.2±2.2 Comparative Example 4 90.3±1.9 Comparative Example 5 88.6±2.0 Comparative Example 6 91.5±1.8

[0369] According to the above test results, Example 2 performs the best and can be considered as the best embodiment of the present application. It performs excellently in terms of strength, solubility, stability, antioxidant capacity and in vitro digestion simulation, etc.

[0370] Upon further analysis of these test data, it can be found that the present application has the following unexpected technical effects:

[0371] 1. Synergistic effect: The synergy between different animal-derived raw materials, combined with the application of complex enzyme preparations, not only improves the strength of the small pellets (37.7% increase in Example 2 compared to Comparative Example 1), but also significantly improves the solubility. This synergistic effect far exceeds the effect of single improvement, reflecting the innovation of the invention in material design.

[0372] 2. Ultra-long-term stability: Through modification and multiple protection mechanisms, the DHA small pellets of the invention still maintain a high DHA content retention rate (96.8%) and a low peroxide value (2.3 meq / kg) under accelerated conditions of high temperature (40°C, 3 months). This result greatly exceeds the stability of traditional DHA preparations, making long-term storage and transportation possible.

[0373] 3. Targeted release characteristics: In vitro digestion simulation experiment results show that the small pellets of the invention achieve a DHA release rate of up to 95.2% in the small intestine stage. This targeted release characteristic is the result of precise design and multiple modification of gelatin complexes, which helps to improve the bioavailability of DHA.

[0374] 4. Multiplication effect of processing technology: The combination of high-frequency pulse jet technology and vacuum microwave drying (Example 2 vs. Comparative Examples 4 and 5) not only improves the uniformity and integrity of the product, but also shows significant advantages in protecting DHA. This synergistic effect of the process is beyond the reach of conventional methods.

[0375] In summary, the invention achieves comprehensive improvement of DHA small pellets in strength, solubility, stability and bioavailability through multiple synergies of material design, formula optimization and process innovation. These unexpected technical effects not only solve the long-standing stability and bioavailability problems of DHA preparations, but also provide new ideas and methods for the design and development of functional foods.

[0376] Experiment Five: Cell Uptake Experiment

[0377] Purpose of the experiment: To evaluate the cell uptake efficiency of DHA in DHA small pellets.

[0378] Experimental method:

[0379] First, the Caco-2 cell line is used as a model of human small intestinal epithelial cells. The cells are cultured at 37°C, 5% CO2, using DMEM medium containing 10% FBS. When the cells grow to 80-90% confluence, they are seeded on a 12-well Transwell plate.

[0380] Second, after the cells are fully differentiated (about 21 days), DHA small pellet solutions of different samples are added to the top chamber of the Transwell plate. The incubation time is set to 2 hours, 4 hours and 6 hours.

[0381] Then, the culture solution in the top and base chambers was collected separately, and the DHA content was determined using gas chromatography-mass spectrometry (GC-MS).

[0382] Finally, the apparent permeability coefficient (Papp) and absorption rate of DHA were calculated.

[0383] Experiment Six: In vivo bioavailability experiment

[0384] Purpose of the experiment: To evaluate the bioavailability of DHA droplet pills in vivo.

[0385] Experimental method:

[0386] First, 40 healthy SD rats were selected and randomly divided into 8 groups (Examples 1-4 and Comparative Examples 1-4, one group each), with 5 rats in each group. The rats were fasted for 12 hours before the experiment and allowed to drink water freely.

[0387] Second, the rats were given DHA droplet pills (dissolved in water) at a dose of 100 mg DHA / kg body weight. Blood samples were collected at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after administration.

[0388] Then, the DHA content in the plasma was determined using liquid chromatography-tandem mass spectrometry (LC-MS / MS).

[0389] Finally, the pharmacokinetic parameters, including maximum plasma concentration (Cmax), peak time (Tmax), and bioavailability (F), were calculated.

[0390] Experimental results:

[0391] Table 5: Results of cell absorption experiment and in vivo bioavailability experiment

[0392] Sample Papp (x 10 -6 cm / s)]]> Bioavailability F (%) Example 1 3.8±0.2 78.5±3.2 Example 2 4.5±0.3 85.3±2.8 Example 3 4.2±0.2 82.7±3.0 Example 4 4.3±0.3 83.9±2.9 Comparative Example 1 2.6±0.2 62.1±3.5 Comparative Example 2 3.0±0.2 68.4±3.3 Comparative Example 3 2.8±0.2 65.2±3.4 Comparative Example 4 3.5±0.3 73.8±3.1 Comparative Example 5 3.2±0.2 70.5±3.2 Comparative Example 6 3.7±0.3 75.9±3.0

[0393] Based on these test results, it can be further confirmed that Example 2 is the best embodiment of the present application. It performs well in both cell absorption and in vivo bioavailability.

[0394] Upon further analysis of these new test data, it can be found that the present application also has the following unexpected technical effects:

[0395] 1. Ultra-high bioavailability: The in vivo bioavailability of Example 2 is as high as 85.3%, far exceeding traditional DHA preparations (usually around 50-60%). This result may be due to the synergistic effect of the unique droplet pill structure and gelatin of the present application, which together improve the absorption efficiency of DHA in the intestine.

[0396] 2. Significant cell permeability: The apparent permeability coefficient (Papp) of Example 2 reached 4.5 × 10⁻⁶. 6 The speed of the DHA droplets is 73% higher than that of Comparative Example 1. This indicates that the DHA droplets of the present invention can cross the intestinal epithelial cell barrier more effectively, thereby improving the absorption rate of DHA.

[0397] 3. Multiple Synergistic Effects: By comparing the results of different embodiments and comparative examples, it is clear that there are significant synergistic effects among the various innovative aspects of this invention (such as the use of multiple animal sources as collagen, the application of compound enzyme preparations, and multiple modification treatments). This synergistic effect is not only reflected in the improvement of a single performance, but also in the comprehensive improvement of multiple performance indicators.

[0398] In summary, these additional test results further confirm the inventiveness and superiority of this invention. Through the organic combination of material design, formulation optimization, and process innovation, this invention achieves breakthrough improvements in several key indicators, including bioavailability, stability, and sensory quality, in DHA droplets. These unexpected technical effects not only provide new solutions for the efficient utilization of DHA but also offer innovative ideas for the development of functional foods, and are expected to have wide applications in nutritional supplements, pharmaceuticals, and other fields.

[0399] The above description is merely an embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principle of the present invention should be included within the scope of the claims of the present invention.

Claims

1. A DHA droplet, characterized in that, The pellet comprises a core liquid and a rubber coating covering the core liquid, wherein: The core fluid comprises the following components in parts by weight: 75-85 parts of DHA algal oil; 5-25 parts sweet orange oil; The rubber sheet comprises the following components in parts by weight: 18-40 parts gelatin; 8-12 parts glycerin; Water 66-100 parts; The gelatin is prepared from the following raw materials in parts by weight: 15-25 portions of pork bones; 15-25 portions of pigskin; 15-25 portions of beef bones; 15-25 parts cowhide; 10-20 portions of fish skin; 10-20 portions of fish scales; The method for preparing the gelatin includes the following steps: (1) Raw material pretreatment: a) After cleaning and degreasing the pork and beef bones, crush them into 3-5mm particles using a food-grade bone grinder. Soak them in a 0.5-1% food-grade citric acid solution for 6-8 hours, and then rinse them with purified water until the pH reaches 6.5-7.

0. b) After cleaning and degreasing the pigskin and cowhide, cut them into small pieces of 1-2cm, soak them in a 0.2-0.4% food-grade sodium bicarbonate solution for 3-4 hours, and then rinse them with purified water until the pH reaches 6.5-7.0; c) After cleaning and degreasing the fish skin and scales, treat them with 0.1-0.2% food-grade ascorbic acid solution for 2-3 hours, then rinse with purified water until the pH reaches 6.5-7.0; (2) Enzymatic pretreatment: Mix the pretreated raw materials according to the formula, add 6 times the weight of purified water, and adjust the pH to 6.8-7.2; Add 0.15-0.25% of a compound enzyme preparation, the composition of which is: Enzymatic hydrolysis is carried out at 44-46℃ for 3-3.5 hours, with stirring every 30 minutes for 2-3 minutes each time; (3) Enzyme inactivation: Slowly adjust the pH to 7.4-7.6, and use a plate heat exchanger to quickly raise the temperature to 62-64℃ and maintain it for 12-15 minutes to ensure complete enzyme inactivation; (4) Gelatin extraction: The enzymatically hydrolyzed mixture is transferred to a multi-stage extraction tank with a temperature gradient, and the total extraction time is 2-2.5 hours. a) Level 1: 64-66℃, 30-40 minutes b) Second level: 68-70℃, 40-50 minutes c) Level 3: 72-74℃, 50-60 minutes After each extraction stage, perform 5 minutes of low-frequency ultrasonic treatment at a frequency of 20-25 kHz and a power of 300-400W. (5) Separation and purification: A combined separation technology of two-step centrifugation and one-step membrane filtration is employed: a) Primary centrifugation: 5000-5500 rpm, 25 minutes b) Fine filtration: Cross-flow filtration using a 100kDa ceramic membrane with a molecular weight cutoff of 0.1-0.2MPa. c) Two-stage centrifugation: 6000-6500 rpm, 20 minutes (6) Concentration: The gelatin solution was concentrated using a two-stage ultrafiltration system. a) First stage: Uses a polyethersulfone membrane with a molecular weight cut of 15 kDa, operating pressure 0.3-0.4 MPa b) Second stage: Using a polyvinylidene fluoride membrane with a molecular weight cut of 5 kDa, operating pressure 0.4-0.5 MPa The final gelatin solution concentration should be controlled at 20-22%. (7) Modification treatment: (8) Drying: Low-temperature vacuum spray drying technology is used: a) Inlet temperature: 75-78℃; b) Outlet temperature: 48-52℃; c) Atomization pressure: 0.22-0.26 MPa; d) Vacuum degree: 60-80 Pa; e) Drying medium: food-grade nitrogen; (9) Crushing and sieving: a) Use a low-temperature airflow mill for pulverization, with the feed temperature controlled at 10-15℃; b) Passed through a 100-mesh stainless steel sieve; c) Use a food-grade electrostatic precipitator for dust removal; d) Use near-infrared spectroscopy to determine the purity of gelatin, ensuring a purity of ≥98%; The compound enzyme preparation includes collagenase, papain, neutral protease, and alkaline protease, wherein the activity of collagenase is ≥200,000 U / g, 40-50%; the activity of papain is ≥600,000 U / g, 30-40%; the activity of neutral protease is ≥100,000 U / g, 15-20%; and the activity of alkaline protease is ≥200,000 U / g, 5-10%. The modification process includes the following steps: (1) Add 0.4-0.8% citric acid and 0.1-0.3% lactic acid to the concentrate and stir until homogeneous; (2) Add 0.2-0.4% sodium hyaluronate and 0.1-0.3% chitosan, and stir for 20-25 minutes; (3) Adjust the pH to 6.9-7.

3.

2. The DHA droplets according to claim 1, characterized in that, The first stage of the two-stage ultrafiltration system has a molecular weight cutoff of 10,000 Da, and the second stage has a molecular weight cutoff of 3,000 Da.

3. A method for preparing DHA droplets as described in any one of claims 1-2, characterized in that, Includes the following steps: (1) Preparation of core solution: Mix 75-85 parts of DHA algal oil with 5-25 parts of sweet orange oil and stir evenly for 30 minutes to obtain a homogeneous core solution; (2) Preparation of gelatin solution: Pour 66-100 parts of water into a gelatin dissolving tank, heat to 70-80℃, dissolve 18-40 parts of gelatin in water, add 8-12 parts of glycerin, stir until the gelatin is completely dissolved and the solution is clear and transparent; then degas under vacuum at 80-85℃ for 8-12 minutes, and keep warm for later use. (3) High-frequency pulse jet technology is used for dripping; the rubber solution and the core liquid form a concentric flow column in a coaxial double-layer nozzle, with the core liquid in the inner layer and the rubber solution in the outer layer. Several synchronous pulse forces are applied to the concentric flow column and evenly distributed along the circumference of the concentric flow column, cutting the concentric flow column into a beaded shape; (4) Immerse the dripped pills in caprylic and caprylic glycerides and refrigerate at 5°C for 4 hours to set. (5) Separation using low-temperature centrifugation technology: Place the shaped pellets in a low-temperature environment of 5-10℃ and centrifuge at a speed of 1500-2000rpm for 5-8 minutes to separate the pellets from the residual cooling medium. (6) Vacuum microwave drying: Place the separated small droplets in a vacuum microwave drying equipment with a microwave power of 200-300W, a vacuum degree of 50-100Pa, a temperature setting of 25℃, and a drying time of 15-20 minutes. Use intermittent mode, turning on for 10 seconds and turning off for 5 seconds to control the final moisture content of the product to be below 3%. (7) Surface treatment using low-temperature plasma technology: Place the dried small droplets in a low-temperature plasma treatment device, use argon as the working gas, gas flow rate 20-30 sccm, radio frequency power 50-100W, treatment pressure 10-50Pa, treatment time 20-30 seconds, and treatment temperature controlled at 25-35℃. (8) Screening: Use an ultrasonic-assisted vibration screening machine with a screen aperture of 6.0±0.2mm, a vibration frequency of 50-60Hz, and a screening time of 2-3 minutes. (9) Perform nitrogen-filled packaging.

4. The preparation method according to claim 3, characterized in that, The parameters of the high-frequency pulse jet technology are as follows: Control the temperature of the rubber liquid to 80-85℃ and the flow rate to 6.0-8.0mL / min; the temperature of the core liquid to 45-50℃ and the flow rate to 3.0-4.0mL / min; the nozzle vibration frequency to 150-200Hz, the nozzle orifice diameter to 0.3-0.5mm, and the dripping height to 20-30cm.

5. The preparation method according to claim 3, characterized in that, The nitrogen-filled packaging employs a multi-stage nitrogen-filled packaging system, including the following steps: (1) First-stage vacuum treatment, with a vacuum degree of 50-100 Pa; (2) Second stage nitrogen purging, nitrogen purity ≥ 99.999%; (3) The third stage is nitrogen purging, with a nitrogen purging pressure of 0.08-0.12 MPa; (4) Heat sealing, temperature is 130-150℃, time is 0.8-1.2 seconds.