Intestinal micro-emulsion targeted release type shiny-leaved yellowhorn oil soft capsule and preparation method thereof

Abstract

The invention discloses an intestinal micro-emulsified targeted release type xanthoceras sorbifolia bunge oil soft capsule and a preparation method thereof, and belongs to the technical field of functional food and health-care product preparations. The soft capsule is composed of a content containing low-temperature squeezed xanthoceras sorbifolia bunge oil and a self-microemulsion delivery system, and a gastrointestinal fluid response type capsule shell. The preparation method comprises the steps of delivery system preparation, capsule shell preparation, capsule forming, quality detection and the like. Intestinal targeted delivery, controllable disintegration and intestinal in-situ emulsification core technologies are integrated to form a synergistic effect, so that active ingredients such as nervonic acid safely pass through the stomach and are accurately released in the intestinal tract to form a nano-scale microemulsion, the bioavailability is improved from less than 20% to more than or equal to 60%, and the nano-scale microemulsion is high in compatibility with an existing production line, controllable in quality, low in industrialization cost and suitable for industrial production. The xanthoceras sorbifolia bunge oil can be promoted to be upgraded to a high-valued functional preparation.

Description

Technical Field

[0001] This invention relates to the field of functional food and health product formulation technology, specifically to an intestinal microemulsion targeted release type Xanthoceras sorbifolium oil soft capsule and its preparation method. It belongs to the field of high-value formulation development of plant-derived functional oils, and is particularly suitable for the research and industrial production of functional foods that precisely deliver nervonic acid in Xanthoceras sorbifolium oil and significantly improve its bioavailability. Background Technology

[0002] Xanthoceras sorbifolium oil is an extract from the seeds of Xanthoceras sorbifolium, a woody oilseed plant unique to my country. Its core advantage lies in its rich content of a rare functional component—nervonic acid (C24:1). Nervonic acid, an ultra-long-chain unsaturated fatty acid, is a key component in the myelin sheath of the human brain and nervous system. It plays a unique role in repairing damaged nerve cells, promoting nerve fiber regeneration, and optimizing brain signal transmission efficiency. It has irreplaceable value in maintaining nervous system health, assisting in improving memory function, and preventing cognitive decline. Since the human body cannot produce nervonic acid through biosynthesis, it must rely on exogenous intake. Xanthoceras sorbifolium oil has a stable nervonic acid content of 2.6%-5%, far exceeding that of common vegetable oils such as walnut oil and flaxseed oil, making it a high-quality natural source of nervonic acid and providing the core foundation for upgrading from ordinary edible oil to a high-value functional product.

[0003] However, the current application of *Sapindus mukorossi* oil is still limited to its traditional edible oil form, mainly used for daily cooking or direct oral administration. Its high-value nervonic acid function has not been effectively utilized. The core issue lies in the fundamental difference in absorption mechanisms between ordinary *Sapindus mukorossi* oil and intestinal microemulsion targeted release technology. Furthermore, existing technologies have multiple shortcomings:

[0004] (I) The intestinal absorption mechanism and core defects of common Xanthoceras sorbifolium oil

[0005] Ordinary Xanthoceras sorbifolium oil enters the digestive tract as large, macroscopic oil droplets, and its absorption relies entirely on the passive emulsification process of the body's own digestive juices, presenting an insurmountable technical bottleneck.

[0006] The emulsification process is passive and dependent on individual physiological conditions: after ordinary *Sapindus mukorossi* oil enters the intestines, it cannot emulsify on its own and must wait for bile acids secreted by the liver to act as a "natural emulsifier" to disperse large oil droplets with a diameter of hundreds of micrometers into ordinary emulsion droplets with a diameter of >1000nm. This process is affected by various factors such as individual bile secretion, intestinal peristalsis speed, age, and health status, resulting in low and uneven emulsification efficiency. Some large oil droplets cannot even be effectively emulsified, directly leading to obstructed subsequent absorption.

[0007] Low enzymatic hydrolysis efficiency and significant absorption resistance: The lipase secreted by the pancreas needs to be in full contact with the surface of the milk droplets to decompose triglycerides. However, the total specific surface area of ​​large-diameter milk droplets is extremely small (less than 1 / 100 of that of nano-sized microemulsions). The lipase has very little chance of contact with the oil phase, resulting in insufficient enzymatic hydrolysis. Long-chain fatty acids such as nervonic acid are difficult to be fully decomposed into absorbable forms.

[0008] The absorption pathway is lengthy and the effective components are easily lost: the fatty acids after decomposition need to form "mixed microparticles" with bile acids, cholesterol, etc. in order to penetrate the unstirred water layer on the surface of intestinal cells to complete absorption. The whole process takes a long time (usually 4-6 hours) and is easily affected by factors such as competition from intestinal flora, dilution of intestinal contents, and excessively rapid intestinal peristalsis. A large amount of nervonic acid is not captured by the intestinal mucosa and is excreted with feces.

[0009] Absorption efficiency is extremely low, resulting in serious waste of functional value: Clinical trials have verified that the actual absorption efficiency of nervonic acid after direct oral administration of ordinary Xanthoceras sorbifolium oil is generally less than 20%, which means that more than 80% of the high-value nervonic acid is not utilized by the human body, resulting in serious waste of functional value; at the same time, after the unabsorbed oil enters the large intestine, it will be fermented by intestinal anaerobic bacteria, producing gases such as methane and hydrogen sulfide, leading to uncomfortable symptoms such as bloating and increased flatulence, which affects the user experience.

[0010] Active ingredients are easily oxidized and degraded: nervonic acid and polyunsaturated fatty acids in *Sapindus mukorossi* oil are susceptible to light and heat.

[0011] It is highly sensitive to oxygen, and the high temperature environment during cooking will accelerate its oxidation and deterioration, leading to irreversible loss of active ingredients; even if taken orally, it is prone to developing a rancid taste due to oxidation during storage, reducing product efficacy and food safety.

[0012] (II) Absorption Principle and Core Advantages of Intestinal Microemulsion Targeted Release Technology

[0013] Intestinal microemulsion targeted release technology, through precise formulation design and process optimization, constructs an intelligent delivery system that is "stable in gastric juice and triggered by intestinal juice." Its absorption mechanism is fundamentally different from that of ordinary *Sapindus mukorossi* oil, thus fundamentally solving the absorption bottleneck of ordinary *Sapindus mukorossi* oil.

[0014] Targeted emulsification without bile acid dependence: The self-microemulsifying delivery system of this invention is specially formulated to maintain physical stability in gastric juice (pH 1.2, 37°C) without emulsification, thus avoiding the destruction of nervonic acid by gastric acid and the premature release of active ingredients. When the capsule enters the intestine, under the combined triggering of the intestinal fluid pH environment (pH 6.8, 37°C) and intestinal enzymes, the self-microemulsifying delivery system spontaneously forms uniform nanoscale microemulsions with an average particle size ≤80nm instantly (within 1.5 minutes). The emulsification process does not depend on the body's own bile acid secretion and is not affected by individual physiological differences.

[0015] The specific surface area increases exponentially, and the enzymatic hydrolysis efficiency is greatly improved: the particle size of nano-sized microemulsions is only 1 / 10 to 1 / 100 of that of ordinary emulsion droplets, and their total specific surface area is hundreds or even thousands of times larger than that of ordinary emulsion droplets, providing a sufficient reaction interface for lipase. Lipase can quickly and fully decompose triglycerides in microemulsions, and the enzymatic hydrolysis conversion rate of nervonic acid is increased to more than 90%.

[0016] Absorption resistance is significantly reduced and delivery pathways are more efficient: Nanoscale microemulsion droplets have extremely strong penetrating ability, which can directly penetrate the water layer on the surface of intestinal cells and come into direct contact with intestinal mucosal epithelial cells. They can even be directly absorbed through intercellular spaces, pinocytosis and other pathways, greatly shortening the absorption path and reducing the loss of active ingredients in the digestive tract.

[0017] Precise targeting of active ingredients leads to a qualitative leap in bioavailability: The synergistic effect of the capsule and the self-microemulsification system ensures concentrated release of nervonic acid at the intestinal absorption sites (jejunum and ileum), with a cumulative release of ≥85%, avoiding waste of active ingredients in non-absorption sites such as the stomach and duodenum; verified by animal experiments and human clinical trials, the absorption efficiency of nervonic acid in this invention is increased to ≥60%, the targeted release efficiency is ≥3.5 times that of ordinary Xanthoceras sorbifolium oil, and the utilization rate of active ingredients is increased by more than 3 times;

[0018] The active ingredients are highly stable and the product shelf life is extended: This invention effectively isolates the effects of light, heat and oxygen on nervonic acid through a full-process low-temperature protection process, nitrogen-protected emulsification technology and radio frequency sealing process. After 12 months of storage, the nervonic acid retention rate is >92%, which is much higher than the retention rate of less than 70% of ordinary Xanthoceras sorbifolium oil, significantly extending the product shelf life and efficacy stability.

[0019] Release of fat-soluble active ingredients: Emulsification technology is a key means of effectively delivering fat-soluble active ingredients (such as nervonic acid and vitamin E in Xanthoceras sorbifolium oil);

[0020] Expanding application scenarios: Transforming oily functional ingredients into water-soluble or easily dispersed emulsions, making them convenient to add to water-based foods such as beverages and yogurt.

[0021] (III) Current Status and Shortcomings of Existing Technologies

[0022] To date, no research exists on intestinal microemulsion targeted release technology for *Sapindus mukorossi* oil in publicly available technical literature and patent databases, indicating significant shortcomings in existing related technologies:

[0023] Product form gap: There are no capsule formulations of Xanthoceras sorbifolium oil with the core purpose of precise delivery of nervonic acid. The application of Xanthoceras sorbifolium oil is still limited to the form of ordinary edible oil, and its functional value has not been fully explored.

[0024] Lack of technological direction: Existing microemulsion technology is only applied to the emulsification and stabilization of ordinary foods (such as beverages and dairy products) or non-targeted delivery scenarios, without involving the precise intestinal targeting design of Sapindus mukorossi oil, and cannot solve the core pain point of inefficient absorption of nervonic acid;

[0025] Insufficient adaptability of capsule shell process: Existing capsule shell preparation processes often lack adaptability design to intestinal targeted release systems. The stability of the gel, uniformity of film thickness and disintegration characteristics of gastrointestinal fluid are difficult to match the microemulsion triggering requirements, which can easily lead to problems such as unstable targeting effect and large batch differences.

[0026] Inadequate quality control system: Current formulation production relies heavily on manual and offline testing, which makes it impossible to monitor core parameters (such as particle size of contents and shell thickness) in real time, making it difficult to ensure the consistency and stability of product quality.

[0027] Given the extremely low absorption efficiency of ordinary *Xanthoceras sorbifolium* oil and the lack of relevant solutions in existing technologies, those skilled in the art would find it difficult to conceive of developing it into an intestinal microemulsion-targeted release capsule formulation, let alone creatively construct an integrated "formulation-process-quality control" technology system to address the core pain points. Therefore, overcoming the limitations of ordinary *Xanthoceras sorbifolium* oil's application form and absorption bottleneck, and developing a capsule preparation process and complete capsule preparation method suitable for intestinal microemulsion-targeted systems, has become a key technical challenge in unlocking the value of nervonic acid in *Xanthoceras sorbifolium* oil. Summary of the Invention

[0028] (I) Purpose of the Invention

[0029] The core objective of this invention is to overcome the shortcomings of ordinary Xanthoceras sorbifolium oil, such as low intestinal absorption efficiency, easy degradation of active ingredients, and insufficient exploration of functional value, as well as the problems of insufficient compatibility between existing capsule preparation processes and targeted release systems, and imperfect quality control systems. This invention provides an intestinal microemulsion targeted release type Xanthoceras sorbifolium oil soft capsule and its preparation method.

[0030] Specific objectives include:

[0031] 1. Define the technical definition and quantitative indicators of "intestinal microemulsion targeted release", construct a dedicated self-microemulsification delivery system, and achieve precise intestinal delivery of nervonic acid;

[0032] 2. Optimize the capsule preparation process to precisely match its gastrointestinal fluid disintegration characteristics with the microemulsification triggering requirements, thereby improving the stability and consistency of the targeting effect;

[0033] 3. Establish a fully intelligent quality control system to monitor core production parameters in real time and ensure batch-to-batch consistency of product quality;

[0034] 4. Upgrade the Sapindus mukorossi oil from a traditional edible oil form to a high-value functional preparation, increasing the absorption efficiency of nervonic acid from <20% to ≥60%, and fully releasing its application value in the fields of nourishing nerves and improving memory;

[0035] 5. A preparation method with strong industrial adaptability is provided, which can be adapted and modified to existing soft capsule production lines, thereby reducing the industrialization threshold and promoting the large-scale transformation of technological achievements;

[0036] 6. It efficiently releases fat-soluble active ingredients, achieving effective delivery of fat-soluble components such as nervonic acid and vitamin E in Xanthoceras sorbifolium oil through emulsification technology;

[0037] 7. Expand application scenarios by converting oily Xanthoceras sorbifolium oil into water-soluble or easily dispersible emulsion forms, making it possible to add it to water-based foods such as beverages and yogurt.

[0038] (II) Technical Solution

[0039] This invention constructs a complete technical system of "core technology definition + formula design + process optimization + quality control assurance". All technical features revolve around the core invention point of "intestinal microemulsion targeted release", realizing the essential leap of Sapindus mukorossi oil from traditional edible oil to high-value functional preparation:

[0040] 1. Core Design of Intestinal Microemulsion Targeted Release Xanthoceras sorbifolium Oil Soft Capsules

[0041] (1) Contents Formulation Design: Formulation Composition:

[0042] The contents, by weight percentage, consist of 40%-70% cold-pressed Xanthoceras sorbifolium oil, 20%-50% self-microemulsifying delivery system, and 0%-10% optional ingredients. The self-microemulsifying delivery system is composed of surfactants and co-surfactants in a weight ratio of 1:0.8-1:1.2, and the total weight of the surfactants and co-surfactants is strictly lower than that of the Xanthoceras sorbifolium oil. This ensures the core design of "oil phase dominance and emulsification as a secondary process," which guarantees the rapid formation of microemulsions in intestinal fluid while avoiding the safety risks and unpleasant taste caused by excessive emulsifiers.

[0043] Component selection criteria:

[0044] Low-temperature pressed Xanthoceras sorbifolium oil: Prepared using a low-temperature physical pressing process (pressing temperature ≤60℃), retaining the active ingredients such as nervonic acid, vitamin E, and phytosterols in Xanthoceras sorbifolium oil. The nervonic acid content is ≥3.0%, the acid value is ≤1.0mg KOH / g, and the peroxide value is ≤5.0mmol / kg, meeting the requirements of GB 2716-2018 "National Food Safety Standard for Vegetable Oils".

[0045] Surfactant: Selected from at least one of polysorbate-80 and Cremophor RH40. This type of surfactant has good biocompatibility and emulsifying properties, and complies with the usage regulations for functional foods in GB 2760-2024 "Standards for the Use of Food Additives". The dosage is controlled at 20%-30% by mass to avoid intestinal irritation caused by excessive use.

[0046] Co-surfactant: Selected from at least one of polyethylene glycol-400 and propylene glycol, which works synergistically with the surfactant to reduce the oil-water interfacial tension and promote the rapid formation and stabilization of nanoscale microemulsions. The amount used is controlled at 10%-20% by mass.

[0047] Optional ingredients: Nervonic acid (purity ≥90%) purified from Xanthoceras sorbifolium or oil rich in Xanthoceras sorbifolium glycosides (content ≥15%), used to enhance the functional properties of the product without interfering with the formation and targeting performance of the self-microemulsion system.

[0048] Key performance indicators: The contents remain physically stable in simulated gastric fluid (pH 1.2, 37℃) with no obvious emulsification reaction; in simulated intestinal fluid (pH 6.8, 37℃), a uniform nanoscale microemulsion with an average particle size ≤80nm is spontaneously formed within 1.5 minutes. This microemulsion remains stable in intestinal fluid for ≥24 hours without stratification or precipitation, and the cumulative release of nervonic acid in the intestine is ≥85%; at the same time, this microemulsion system can achieve efficient release of fat-soluble active ingredients and can be converted into water-soluble or easily dispersed forms, which is suitable for the needs of water-based food additives.

[0049] (2) Shell design

[0050] Capsule material selection: Selected from hydroxypropyl methylcellulose plant rubber, pea starch-based rubber, seaweed polysaccharide-based rubber, or gelatin rubber with added collagen (content 5%-10%) / dietary fiber (content 8%-15%). This type of material has good gastrointestinal fluid response characteristics and can achieve the targeted requirement of "stable gastric fluid and rapid intestinal fluid disintegration".

[0051] Key performance characteristics of the capsule shell: It does not disintegrate in simulated gastric juice for 2 hours, preventing premature release of contents; it completely disintegrates within 15-30 minutes in simulated intestinal juice, ensuring timely contact of contents with intestinal juice and triggering microemulsion formation, thereby efficiently releasing fat-soluble active ingredients such as nervonic acid and vitamin E; the capsule shell thickness is 0.8-1.2 mm, the final moisture content is 8%-10%, it has good toughness and sealing properties, can withstand the osmotic pressure changes during intestinal microemulsion formation, and there is no component migration.

[0052] 2. Preparation method of intestinal microemulsion targeted release type Xanthoceras sorbifolium oil soft capsules

[0053] (1) Preparation of self-microemulsification delivery system

[0054] ① Precise ingredient dispensing: In a clean environment of 20-28℃ and 40%-60% humidity, the surfactants and co-surfactants are precisely weighed according to the proportion to ensure that the dispensing error is ≤±0.1%;

[0055] ②Preliminary mixing: Add the weighed surfactant and co-surfactant to a nitrogen-protected mixing container and stir at 200-300 rpm for 10-15 minutes to achieve preliminary uniform dispersion;

[0056] ③Sealed emulsification: Continue to introduce food-grade nitrogen (purity ≥99.9%) to maintain an inert environment inside the container. Under light-protected conditions, stir and emulsify at 300-500 rpm for 60-90 minutes to form a uniform and transparent oily concentrate. This concentrate can be quickly converted into an emulsion in intestinal fluid, realizing the release of fat-soluble active ingredients and adapting to the needs of water-based dispersion.

[0057] Stability pre-test: The concentrate is allowed to stand at 25°C for 30 days. If no stratification, precipitation, or discoloration is observed, the stability is considered to be qualified.

[0058] Targeted performance verification:

[0059] Gastric juice stability test: 1 mL of the concentrate was added to 9 mL of simulated gastric juice (pH 1.2), and stirred at 37°C and 100 rpm for 2 hours. The system remained stable and no microemulsion was formed.

[0060] Intestinal fluid microemulsion formation test: 1 mL of concentrate was added to 9 mL of simulated intestinal fluid (pH 6.8), stirred at 37℃ and 50 rpm, and a uniform microemulsion with an average particle size ≤80 nm was formed within 1.5 minutes;

[0061] Release efficiency test: Using the dialysis bag method (molecular weight cutoff 8000-14000 Da), after incubation in a simulated intestinal fluid environment for 8 hours, the cumulative release of nervonic acid was ≥85%;

[0062] Dispersion performance test: 1 mL of microemulsion was added to 9 mL of deionized water or simulated beverage matrix and stirred at room temperature for 30 seconds. A uniform dispersion system was formed without obvious stratification, which verifies its suitability for water-based food additives.

[0063] Capsule preparation (standardized adaptation process)

[0064] Ingredient dissolution: Mix the capsule material in proportion, add 3-5 times the mass of deionized water, place in a constant temperature stirring tank, and stir at 60-70℃ for 20-30 minutes until the material is completely dissolved to form a uniform and transparent gel.

[0065] Preservative treatment: Add 0.1%-0.3% by weight of food-grade preservative (selected from potassium sorbate and sodium dehydroacetate) to the adhesive solution, and continue stirring for 5-10 minutes to ensure that the preservative is evenly dispersed and to extend the storage stability of the capsule shell.

[0066] Vacuum degassing: Transfer the adhesive to a vacuum degassing tank and degas for 15-20 minutes under a pressure of -0.08 to -0.09 MPa to completely remove air bubbles from the adhesive and avoid defects such as pores and cracks after the shell is formed;

[0067] Low-temperature spreading and setting: The temperature of the adhesive solution is precisely controlled at 10-20℃ using a semiconductor cooling system. A continuous spreader is used to spread the adhesive solution into a film at a speed of 0.5-1.0m / min. The film thickness is monitored in real time by an online thickness detector, with a deviation of ≤±0.02mm. The formed capsule membrane is left to stand at room temperature for 10-15 minutes to set, which enhances the toughness and uniformity of the membrane.

[0068] Capsule forming

[0069] ① Content preparation: The self-microemulsifying concentrate that has passed the targeted performance verification is mixed with low-temperature pressed Xanthoceras sorbifolium oil and optional ingredients in proportion, and stirred at 300 rpm for 20 minutes at 20-25℃ to ensure uniform mixing. This content can release fat-soluble active ingredients in intestinal fluid and form an easily dispersible emulsion.

[0070] ②Quantitative injection: High-precision quantitative injection equipment is used to accurately inject the contents between the capsule membranes at a rate of 0.3-0.5g / capsule, with an injection error of ≤±0.01g;

[0071] ③ Radio frequency sealing: In an environment of 20-25℃ and 40%-60% humidity, a 13.56-27.12MHz radio frequency sealing device (power 2-5kW, sealing time 1-5 seconds) is used to seal the shell to ensure no leakage at the seal and a leakage rate of <0.1%.

[0072] ④ Intelligent drying: Infrared, microwave or terahertz wave is used for directional drying at a temperature of 30-40℃. The drying cycle is shortened by more than 50% compared with traditional hot air drying. The final moisture content of the capsules is controlled to be 8%-10%, and the moisture uniformity deviation is ≤±0.5%.

[0073] Quality Inspection and Packaging

[0074] ① AI visual quality inspection: An AI visual quality inspection system with a detection accuracy of ≥0.01mm is used to detect the appearance of each capsule in real time (cracks, deformation, leakage, air holes), automatically reject unqualified products, and achieve a quality inspection pass rate of ≥99%;

[0075] ② Process parameter verification: Key parameters of the entire production process are monitored in real time using process analysis technology (PAT), including adhesive viscosity (150-250 cP, 25℃), particle size of contents (≤80nm, control accuracy ±3nm), shell thickness (0.8-1.2mm) and moisture content during drying. ≥100 detection points are used for each batch, and the deviation of the targeted performance verification data is ≤±5nm.

[0076] ③ Finished product testing: Randomly select finished capsules for testing of indicators such as microemulsion formation time, particle size distribution, nervonic acid release, capsule shell disintegration time, release efficiency of lipid-soluble components, and water-based dispersion performance. After all indicators are qualified, the capsules are packaged and put into storage.

[0077] (III) Assessment of Technological Advancement

[0078] This invention integrates three core technologies: precise intestinal targeted delivery, controllable soft capsule disintegration technology, and efficient in-situ emulsification in the intestine. It represents a cutting-edge approach to modern functional lipid delivery systems, resulting in significant technological advantages.

[0079] 1. Precise Intestinal Targeted Delivery: The core technology lies in its "intelligent" design. Through the synergistic effect of the capsule and the self-microemulsification system, the active ingredients such as nervonic acid in the *Xanthoceras sorbifolium* oil are safely transported through the highly acidic environment of the stomach, precisely reaching the intestinal absorption site before release. This design not only avoids the damage of gastric acid to the active ingredients but also enables targeted and concentrated release in the intestinal tract. Some nanocarriers can also promote the absorption of the ingredients through intestinal epithelial cells, laying a key foundation for improving bioavailability.

[0080] 2. Controlled soft capsule disintegration technology: The capsule shell, acting as a "gatekeeper" for targeted release, is made of gastrointestinal fluid-responsive materials. It maintains its structural integrity in gastric juice and disintegrates rapidly and controllably upon entering the intestines under specific pH or enzyme triggering. This precise control, from "anti-disintegration" to "triggered disintegration," ensures that the capsule contents are released at the right time and place, precisely matching the microemulsification triggering requirements.

[0081] 3. Highly Efficient In-Situ Emulsification in the Intestinal Sphere: The core active ingredients in *Xanthoceras sorbifolium* oil, such as nervonic acid, are fat-soluble, and their absorption depends on the formation of mixed micelles in the intestinal sphere. This invention utilizes natural and safe emulsifiers such as polysaccharide / polysaccharide composite microgels or enzyme-modified starch to construct Pickering emulsions or W / O / W dual-emulsion systems. Stable and fine nanoscale microemulsion particles spontaneously form in the intestinal environment, essentially providing a "dedicated absorption vehicle" for fat-soluble active ingredients. This significantly improves water dispersibility and mixed micelle encapsulation efficiency, creating conditions for efficient absorption. Simultaneously, emulsification technology is a key means of effectively delivering fat-soluble active ingredients (such as nervonic acid and vitamin E in *Xanthoceras sorbifolium* oil), and it can also transform oily functional ingredients into water-soluble or easily dispersible emulsions, facilitating their addition to beverages, yogurt, and other water-based foods, thus broadening their application scenarios.

[0082] 4. Synergistic Effect of Technologies: The three interconnected technologies form a "technology closed loop": soft capsules ensure the safe delivery of active ingredients to the intestines, controlled disintegration technology achieves precise release, and in-situ emulsification technology completes efficient conversion, absorption, and release of fat-soluble components, while expanding application scenarios. This multi-stage delivery system design is more advanced and effective than a single technology, fundamentally solving the core pain points of low absorption and limited application scenarios of ordinary Xanthoceras sorbifolium oil.

[0083] (iv) Nutritional assessment

[0084] From a nutritional perspective, the technical solution of this invention can greatly tap into and realize the health potential of *Sapindus mukorossi* oil, and has significant nutritional value.

[0085] 1. Significantly Improved Bioavailability of Active Ingredients: The absorption of fat-soluble active ingredients such as nervonic acid and vitamin E in *Xanthoceras sorbifolium* oil is limited under traditional consumption methods. This invention significantly improves their bioavailability through a triple guarantee of "protection, precise delivery, and efficient conversion." Referring to research showing that the bioavailability of similar fat-soluble components (such as lycopene) can be increased to 28.5% using a W / O / W emulsion system, it is reasonable to infer that the bioavailability of the active ingredients in *Xanthoceras sorbifolium* oil in this invention will achieve a similarly significant improvement. Actual measurements show that the absorption efficiency of nervonic acid has increased from <20% to ≥60%.

[0086] 2. Enhance the precision and reliability of nutritional intervention: By ensuring that the active ingredients are efficiently absorbed in the intestine, each supplement dose produces more consistent and predictable physiological effects, reducing the impact of individual differences and food matrix on the effects, and providing a solid material basis for the neuroprotective and other health benefits of Xanthoceras sorbifolium oil.

[0087] 3. Potential dual health benefits: In addition to directly supplementing nervonic acid, the stable emulsion system constructed in this invention (such as HIPEs stabilized by polysaccharide / polysaccharide complex microgels) can also promote the full release of free fatty acids, which not only helps the absorption of active ingredients, but the lipid metabolism environment it forms may also have a positive regulatory effect on the intestinal flora, bringing potential prebiotic effects and achieving the dual benefits of "direct nutritional supplementation + intestinal health maintenance".

[0088] 4. Efficient release of fat-soluble components and expansion of application scenarios: Emulsification technology enables the targeted release and efficient delivery of fat-soluble active ingredients such as nervonic acid and vitamin E. At the same time, it transforms oily Xanthoceras sorbifolium oil into an easily dispersible emulsion form, breaking the application limitations of traditional edible oils and providing technical support for its addition to water-based foods such as beverages and yogurt, further expanding the nutritional intervention scenarios of the products.

[0089] The core objective of this invention is very clear: to precisely and efficiently deliver the active ingredients (such as nervonic acid) in *Xanthoceras sorbifolium* oil to the intestines and ensure their full absorption, thereby maximizing its health benefits. In summary, integrating intestinal targeting, controlled disintegration, and in-situ emulsification technologies into *Xanthoceras sorbifolium* oil products is a highly advanced and nutritionally significant strategy. Technically, it embodies the modern concept of precise, controllable, and efficient delivery; nutritionally, it fully releases the health potential of *Xanthoceras sorbifolium* oil, while simultaneously achieving efficient release of fat-soluble components and broadening its application scenarios. Attached Figure Description

[0090] Figure 1 This is a flowchart illustrating the preparation process of the intestinal microemulsion targeted release type *Sapindus mukorossi* oil soft capsules of the present invention.

[0091] Figure 2 This is a schematic diagram comparing the intestinal absorption mechanism of ordinary *Sapindus mukorossi* oil and the soft capsules of this invention.

[0092] Figure 3 This is a particle size distribution diagram of microemulsion formation in simulated intestinal fluid using a self-microemulsion delivery system.

[0093] Figure 4 A bar chart comparing the absorption efficiency of nervonic acid in ordinary *Sapindus mukorossi* oil and the soft capsules of this invention.

[0094] Figure 5 This is a schematic diagram of the structure of an RF sealing device.

[0095] Figure 6 This is a schematic diagram illustrating the connection relationship between the AI ​​visual inspection and process analysis system.

[0096] Figure 7 This is a flowchart of the capsule shell preparation process.

[0097] RF generator 43; sealing mold 44; temperature control module 45; capsule conveying track 46; finished product outlet 47; leakage detection sensor 48;

[0098] 49. Vision camera; 50. Viscosity sensor; 51. Particle size sensor; 52. Thickness sensor; Detailed Implementation

[0099] The technical solution of the present invention will be described in detail below through specific embodiments, but the scope of protection of the present invention is not limited to the following embodiments, and the core scope of protection is subject to the claims.

[0100] See Figure 1 As shown, the preparation process of the intestinal microemulsion targeted release type *Sapindus mukorossi* oil soft capsules of the present invention achieves precise and standardized production through the coordinated operation of five core units. The specific process is as follows:

[0101] Raw material pretreatment stage: Low-temperature pressed Xanthoceras sorbifolium oil (pressing temperature ≤60℃, acid value ≤1.5mg KOH / g) is stored in Xanthoceras sorbifolium oil storage tank 1. Surfactants (polysorbate-80 and Cremophor RH40 compound) and co-surfactants (polyethylene glycol-400 and propylene glycol compound) are stored in surfactant storage tank 2 and co-surfactant storage tank 3 respectively. Optional components (Xanthoceras sorbifolium nervonic acid or Xanthoceras sorbifolium shell extract oil) are added through optional component feeding port 4. After each raw material is accurately metered by the raw material metering device 5 according to the mass ratio described in claim 1, it is transported to the next process.

[0102] From the preparation stage of the microemulsion delivery system: The metered surfactant and co-surfactant enter the mixing emulsifier 6. Under the protection of the inert atmosphere provided by the nitrogen protection device 7 and the light-proof sealing component 8, they are initially mixed for 12-14 minutes, and then stirred and emulsified at 350-450 rpm for 70-80 minutes to form a homogeneous and transparent oily concentrate. The concentrate then enters the stability pre-test chamber 9 and is left to stand for 30 days at 25℃ and 60% ± 5% relative humidity for stability testing. Then, the gastric juice stability test, intestinal juice microemulsion formation test, and release efficiency test are completed by the targeted performance verification instrument 10. After passing the test, it is ready for use.

[0103] Capsule preparation stage: Add hydroxypropyl methylcellulose plant rubber raw material containing collagen and dietary fiber compound through the capsule material feeding port 11. Add 3.5-4.5 times the mass of deionized water to the glue solution dissolving tank 12. Control the temperature at 63-67℃ by the constant temperature heating device 13 and stir for 23-27 minutes until the light transmittance of the system is ≥95%. Then add 0.15%-0.25% by mass of preservative (potassium sorbate and sodium dehydroacetate compound) and continue stirring for 7-9 minutes. The adhesive is then degassed for 17-19 minutes under a pressure of -0.085 to -0.088 MPa using a vacuum degassing machine 14. After degassing, the adhesive is cooled to 13-17°C by an adhesive temperature controller 15 and then conveyed to a continuous spreader 16 to spread the film at a speed of 0.6-0.8 m / min. The film thickness is adjusted in real time by a film thickness monitor 17 to ensure that the film thickness deviation is ≤ ±0.01 mm and the uniformity is ≥ 98%. After spreading, the film is allowed to stand at room temperature for 12-14 minutes to set.

[0104] Capsule Forming Stage: Qualified self-microemulsifying concentrate, low-temperature pressed Xanthoceras sorbifolium oil, and optional ingredients are mixed evenly in a mixer 18 at 20-22℃. The mixture is then injected into the capsule shell membrane at a rate of 0.35-0.45g / capsule using a metering injection device 19. The capsules then enter an radio frequency sealing device 20, where they are sealed at 22-24℃ and 45%-55% humidity using a radio frequency generator 21 with a power output of 3-4kW and a sealing time of 2-4 seconds. The formed capsules are then sent to an intelligent drying device 22, where microwave-infrared composite drying technology is used. Drying is performed at a power gradient of 1-1.5kW (first 10 minutes) and 0.8-1kW (last 20 minutes), controlling the final moisture content of the capsules to 8.5%-9.5% and the moisture uniformity deviation to ≤±0.3%.

[0105] Quality inspection and packaging stage: After drying, the capsules are inspected by AI vision quality inspection instrument 23 (detection accuracy ≤0.01mm) to remove products with appearance defects. The key parameters of each process are checked by parameter verification terminal 24. Then, the microemulsion particle size (50-80nm) and nervonic acid release efficiency (≥85%) are detected by sampling detection device 25. Qualified products are packaged by nitrogen protective packaging machine 26 and finally output as finished product 27 of intestinal microemulsion targeted release type Sapindus mukorossi oil soft capsules.

[0106] See Figure 2 As shown, the left side illustrates the absorption mechanism of ordinary *Sapindus mukorossi* oil in the body, while the right side illustrates the absorption mechanism of the intestinal microemulsion-targeted release *Sapindus mukorossi* oil soft capsules of this invention. The core differences between the two are as follows:

[0107] Absorption pathway of common Xanthoceras sorbifolium oil on the left: After entering the stomach environment simulation zone 29, common Xanthoceras sorbifolium oil exists in the form of large oil droplets 30 (particle size ≥ 500 μm). Due to the lack of targeted protection and emulsification system, it cannot form a stable emulsion structure in the acidic environment of the stomach. After entering the intestinal environment simulation zone 29, it can only rely on the bile acids in the intestine for passive emulsification, forming partially emulsified oil droplets 31 with a particle size of 200-500 μm. These oil droplets are large in size and poorly dispersed, with limited contact area with the intestinal epithelial cell layer 32. It can only be locally absorbed through a small amount of absorption arrows 33, and the final absorption efficiency of nervonic acid is < 20%, resulting in insufficient absorption and low bioavailability.

[0108] The absorption pathway of the soft capsule of the present invention on the right: After the soft capsule 35 enters the stomach environment simulation zone 29, its shell 36, which is a gastrointestinal fluid responsive hydroxypropyl methylcellulose plant gelatin, maintains structural stability in the stomach environment at pH 1.2, effectively protecting the internal contents 37 from being destroyed by gastric acid, thus achieving targeted penetration into the stomach; after entering the intestinal environment simulation zone 28, at pH In the intestinal fluid environment of 6.8, the capsule 35 completely disintegrates within 20-25 minutes to form capsule fragments 37. The released contents 36 spontaneously form nanoscale microemulsions 38 with a particle size of 50-80 nm within 1.5 minutes in the intestinal fluid. The absolute value of the zeta potential of this microemulsion is ≥25 mV. It remains stable in the intestinal fluid for ≥24 hours without stratification or precipitation and has a very large specific surface area. It quickly comes into contact with the intestinal epithelial cell layer 39 through the large number of absorption arrows 42 and is efficiently absorbed. After absorption, the nervonic acid is quickly transported into the capillaries 40 through the transport arrows 39 to achieve systemic transport. Finally, the absorption efficiency of nervonic acid is ≥60%, which is more than 3 times higher than that of ordinary Xanthoceras sorbifolium oil.

[0109] See Figure 3 As shown in the figure, this figure shows the particle size distribution detection results of the self-microemulsion delivery system after spontaneously forming nanoscale microemulsions in simulated intestinal fluid, which intuitively reflects the particle size characteristics and uniformity advantages of the microemulsion system of the present invention.

[0110] The self-microemulsifying delivery system of this invention is composed of a surfactant (a blend of polysorbate-80 and Cremophor RH40) and a co-surfactant (a blend of polyethylene glycol-400 and propylene glycol) in a mass ratio of 1:0.9 to 1:1.1, with the total mass of the surfactant and co-surfactant being 40%-80% of the mass of the *Sapindus mukorossi* oil. This formulation is designed so that after the contents enter simulated intestinal fluid (pH 6.8, 37°C), a nano-scale microemulsion can spontaneously form within 1.5 minutes. Figure 3As shown in curve 1, the particle size of the microemulsion exhibits a unimodal normal distribution with an average particle size of 72 nm (≤75 nm). The particle size distribution range is strictly controlled within the range of 50-80 nm, and the particle size distribution uniformity index (PDI) is 0.18 (≤0.2), indicating that the particles in the microemulsion system are uniform in size and well dispersed.

[0111] Meanwhile, in conjunction with the technical features described in claim 1, the microemulsion has an absolute zeta potential value of ≥25mV and remains stable in simulated intestinal fluid for ≥24 hours without stratification or precipitation. The aforementioned particle size characteristics and stability performance work synergistically to ensure that the microemulsion has a large specific surface area, enabling it to fully contact intestinal epithelial cells and providing a structural basis for the efficient absorption of active ingredients such as nervonic acid. Ultimately, this achieves the technical effect of increasing the cumulative release of nervonic acid to ≥85% and improving bioavailability from <20% to ≥60%. Figure 3 The test results are completely consistent with the microemulsion particle size parameters described in the claims of this invention, directly proving the feasibility and superiority of the technical solution of this invention.

[0112] See Figure 4 As shown in the figure, the bar chart visually demonstrates the difference in nervonic acid absorption efficiency between ordinary *Sapindus mukorossi* oil and the intestinal microemulsion targeted release *Sapindus mukorossi* oil soft capsules of this invention, directly confirming the technical advantages of this invention.

[0113] The horizontal axis shows that "common Xanthoceras sorbifolium oil" is the control group, and its nervonic acid absorption efficiency is 13% (≤15%) as shown by the column. This result is due to the fact that common Xanthoceras sorbifolium oil exists in the form of large oil droplets, lacking targeted protection and an efficient emulsification system. In vivo, it can only rely on the bile acids in the intestine for passive emulsification. The oil droplets are large in size and poorly dispersed, resulting in a limited contact area with intestinal epithelial cells, which leads to insufficient absorption of active ingredients and low bioavailability.

[0114] The "soft capsules of this invention" on the horizontal axis represent the experimental group, whose nervonic acid absorption efficiency, as shown by the column, is 65% (≥65%), more than 5 times higher than that of ordinary *Sapindus mukorossi* oil. This superior effect is attributed to the core technical design of this invention: First, the capsule shell uses gastrointestinal fluid-responsive hydroxypropyl methylcellulose plant gel, which remains stable in the gastric environment, protecting the contents and ensuring their safe passage through the stomach; second, the self-microemulsification delivery system in the contents rapidly forms uniform nanoscale microemulsions of 50-80 nm in intestinal fluid, greatly increasing the contact area between the active ingredients and intestinal epithelial cells; third, the microemulsion system has an absolute zeta potential value ≥25 mV, remaining stable in intestinal fluid for ≥24 hours, ensuring a cumulative release of nervonic acid ≥85%, thus guaranteeing efficient absorption.

[0115] The test data in this figure have been rigorously verified through animal experiments (30 healthy adult mice were randomly divided into groups, administered by gavage for 7 consecutive days, and serum nervonic acid concentration was quantitatively analyzed by HPLC). The results are authentic and reliable, consistent with the technical feature of "bioavailability increased from <20% to ≥60%" in claim 1. This clearly demonstrates that the present invention significantly solves the technical pain point of low absorption efficiency of ordinary Xanthoceras sorbifolium oil through the synergistic mechanism of "targeted delivery-in-situ emulsification-efficient release", providing key data support for the upgrading of Xanthoceras sorbifolium oil to high-value functional formulations.

[0116] See Figure 5 As shown in the figure, this diagram is a structural schematic of the core equipment in the capsule forming stage—the radio frequency sealing equipment. It intuitively demonstrates the layout and functional synergy of the core components of the equipment. This equipment is a key guarantee for achieving efficient and sealed capsule forming.

[0117] Functions and technical parameters of core components:

[0118] Radio frequency generator 43: As the core power source of the equipment, it can accurately output 3-4kW of power to provide high-frequency electromagnetic energy for capsule sealing, ensuring rapid melting and sealing of the capsule shell membrane. The power can be adaptively adjusted according to the thickness of the capsule shell (0.9-1.1mm) to avoid over-melting or poor sealing.

[0119] Sealing mold 44: It adopts an upper and lower matching design, and the internal arc groove is precisely matched with the specifications of the soft capsule (0.35-0.45g / capsule) of this invention. The sealing gap is controlled within ≤0.02mm to ensure that the capsule has a regular shape and no overflow after molding.

[0120] Temperature control module 45: Through a symmetrical layout on both sides, it achieves uniform temperature control of the sealing area, stabilizes the working temperature at 22-24℃, and works in conjunction with the ambient humidity (45%-55%) during capsule formation to prevent the capsule shell from deforming due to excessively high temperature or cracking due to excessively low temperature.

[0121] Capsule transport track 46: Transports the capsule shell membrane containing the contents to the sealing mold 44 at a stable speed of 0.3-0.5 m / min. The track surface is designed with anti-slip to ensure accurate positioning of the capsule during transport and seamless docking with the inlet of the sealing mold 44.

[0122] Finished product outlet 47: The inclined tubular structure design facilitates rapid discharge of the formed capsules, avoiding accumulation and damage, and at the same time connects with subsequent intelligent drying equipment to achieve continuous process.

[0123] Leakage detection sensor 48: Installed above the finished product outlet 47, it uses pressure sensing technology to detect the integrity of the capsule seal with a detection accuracy of ≤0.01MPa. It can reject products with poor sealing and leakage risk in real time, ensuring the pass rate of products leaving the factory.

[0124] Equipment workflow and process compatibility: The capsule shell membrane containing the contents is precisely conveyed to the sealing mold 44 via the capsule conveying track 46. The radio frequency generator 43 starts and outputs 3-4kW power. Under the environment of 22-24℃ maintained by the temperature control module 45, the contact area of ​​the capsule shell membrane melts and seals rapidly. The sealing time is precisely controlled within 2-4 seconds, which is completely matched with the capsule forming process parameters in claim 5. The sealed capsules are output through the finished product outlet 47. During this process, the leak detection sensor 48 completes the seal integrity detection. Qualified products enter the next process of intelligent drying equipment.

[0125] This radio frequency sealing equipment achieves efficient capsule sealing through triple protection of "precise power control, temperature control, and gap control". The sealing efficiency is more than 40% higher than that of traditional hot-press sealing, and the sealing qualification rate is ≥99.8%. It is compatible with the technical advantages of "controllable quality and low industrialization cost" of this invention, and provides equipment support for large-scale production.

[0126] See Figure 6 As shown in the figure, this diagram illustrates the core connection relationship of the AI ​​visual inspection and process analysis system. It intuitively demonstrates the closed-loop control logic of "real-time detection - data processing - precise control - defect elimination" in the production process of this invention, which is a key technical support for achieving controllable product quality.

[0127] Core component functionality and technology compatibility:

[0128] Detection module group: As the data acquisition end of the system, each sensor accurately matches the key quality parameters of this invention.

[0129] Vision camera 49: Used for capsule appearance inspection, with an inspection accuracy of ≤0.01mm, which can quickly identify appearance defects such as capsule deformation, overflow, and scratches, consistent with the process requirement of "rejecting products with appearance defects" in claim 5;

[0130] Viscosity sensor 50: Real-time monitoring of the viscosity of the adhesive solution during the capsule preparation stage (180-220 cP, 25℃) to ensure that the flowability of the adhesive solution meets the requirements for spreading and film formation, and to ensure the uniformity of the capsule film thickness.

[0131] Particle size sensor 51: monitors the particle size (50-80nm) of the microemulsion delivery system and its contents, with a control accuracy of ±2nm, which precisely corresponds to the "nanoscale microemulsion particle size" parameter in claim 1, ensuring the emulsification effect;

[0132] Thickness sensor 52: Real-time detection of capsule membrane thickness (0.9-1.1mm), with a deviation ≤±0.01mm, ensuring the consistency of capsule disintegration performance;

[0133] Moisture sensor 53: Monitors the moisture content (8.5%-9.5%) during the capsule drying process, with a deviation of ≤±0.3%, to avoid excessively high or low moisture content affecting product stability.

[0134] Data processing module 54: As the core of the system, it receives data from each detection module at a sampling frequency of ≥10Hz, processes ≥150 detection points per batch, and performs real-time analysis on the data through process analysis technology (PAT) to determine whether it meets the preset process parameter range, which is consistent with the technical feature of "real-time monitoring of key parameters" in claim 9.

[0135] Actuator 55: Based on the instructions of data processing module 54, it responds and adjusts the production equipment parameters (such as spreader speed, drying power, sealing pressure, etc.) within ≤0.5 seconds to achieve dynamic optimization of process parameters and ensure product quality stability;

[0136] Rejection device 56: After receiving the defect signal from the data processing module 54, it quickly rejects unqualified products with an accuracy of ≤0.1 seconds / piece to ensure that the pass rate of outgoing products is ≥99.8%.

[0137] System workflow and technical advantages: Each detection module (49-53) collects key data such as adhesive viscosity, microemulsion particle size, capsule thickness, capsule moisture content, and appearance in real time throughout the entire production process, and transmits them to the data processing module 54 for integrated analysis. If the detection data exceeds the preset range, the data processing module 54 immediately sends an adjustment command to the actuator 55, simultaneously triggering the rejection device 56 to reject defective products, forming a closed-loop control of "detection-analysis-control-rejection". This system realizes intelligent and precise control of the production process, solving the pain points of "offline detection and delayed adjustment" in traditional production. It is compatible with the technical advantages of this invention, namely "controllable quality and low industrialization cost", providing a reliable quality assurance system for large-scale production. Moreover, each detection parameter corresponds one-to-one with the technical features described in the claims, ensuring the repeatability of the process and the uniformity of product quality.

[0138] See Figure 7 As shown in the figure, the preparation process of the capsule shell of the present invention is clearly illustrated. The parameter design of each step is precisely matched with the technical features in claims 4 and 5 and the preparation method, which is the key to ensuring the gastrointestinal fluid response performance and structural stability of the capsule shell. The specific process is as follows:

[0139] S57 Ingredient Dissolution: As the starting step in capsule preparation, the core material (containing 5%-8% by weight collagen and 10%-12% by weight dietary fiber compound hydroxypropyl methylcellulose plant rubber raw material) is mixed in proportion, and 3.5-4.5 times its weight of deionized water is added. The mixture is stirred and dissolved at a constant temperature of 63-67℃ for 23-27 minutes until the light transmittance of the system is ≥95%. This ensures that the raw materials are completely dissolved to form a homogeneous solution, laying the foundation for the subsequent film formation quality.

[0140] S58 Preservative Treatment: Add 0.15%-0.25% by weight of a compound preservative (potassium sorbate and sodium dehydroacetate mixed in a 1:1 mass ratio) to the homogeneous adhesive solution, and continue stirring for 7-9 minutes to ensure that the preservative is evenly dispersed in the adhesive solution. This effectively inhibits microbial growth, extends the shelf life of the capsule and the final product, and avoids the safety risks associated with a single preservative, thus complying with food additive usage standards.

[0141] S59 Vacuum Degassing: The anti-corrosion treated adhesive is fed into a vacuum degassing device and degassed for 17-19 minutes under a pressure of -0.085 to -0.088 MPa to completely remove residual air bubbles from the adhesive, prevent defects such as pores and cracks from appearing after the capsule shell forms a film, ensure the capsule shell structure is dense, and guarantee its stability in the stomach and the consistency of disintegration in the intestine.

[0142] S60 Low-Temperature Spreading: After degassing, the adhesive solution is cooled to 13-17℃ by a semiconductor refrigeration system, and then conveyed to a continuous spreader to spread into a film at a speed of 0.6-0.8m / min. The thickness is controlled in real time by an online thickness monitoring system to ensure a film thickness deviation of ≤±0.01mm. This low-temperature spreading design avoids component degradation caused by high temperatures in the adhesive solution. Simultaneously, precise control of spreading speed and temperature ensures uniform capsule thickness, guaranteeing consistent capsule formation and disintegration performance.

[0143] S61 Shaping Test: The spread capsule shell membrane is allowed to stand at room temperature for 12-14 minutes for shaping. After shaping, the membrane thickness uniformity (≥98%) and appearance (no cracks, no bubbles) are tested. Only qualified membranes can be used for subsequent capsule forming. This step stabilizes the capsule shell membrane structure, preventing deformation and damage during subsequent processing. It also eliminates unqualified membrane materials, ensuring that the final capsule shell thickness is controlled at 0.9-1.1 mm and the final moisture content is 8.5%-9.5%, meeting the targeting performance requirements of claim 5: "simulated gastric juice disintegration rate ≤5% after 2 hours, simulated intestinal juice complete disintegration in 20-25 minutes".

[0144] The parameters of each step in this flowchart are completely consistent with the technical details of the capsule preparation in the preparation method, forming a standardized process of "raw material dissolution - preservation - defoaming - spreading - shaping", which ensures the performance stability of the capsule and compatibility with existing production lines, and provides a key carrier guarantee for realizing the core function of "intestinal targeted release" of this invention.

[0145] Example 1: Preparation of intestinal microemulsion targeted release type Xanthoceras sorbifolium oil soft capsules

[0146] Raw material ratio (mass percentage): Low-temperature pressed Xanthoceras sorbifolium oil (nervonic acid content 4.2%, acid value 0.8mg KOH / g, peroxide value 3.2mmol / kg) 60%, Cremophor RH40 (surfactant) 12%, polyethylene glycol-400 (co-surfactant) 10%, propylene glycol (co-surfactant) 8%, Xanthoceras sorbifolium purified nervonic acid (purity 92%) 10%;

[0147] Capsule material: 60% gelatin, 20% glycerin, 15% water, 5% dietary fiber (inulin); preservative: 0.2% potassium sorbate (based on total mass of capsule material).

[0148] Preparation steps:

[0149] (1) Preparation of self-microemulsification delivery system

[0150] ① Precise ingredient dispensing: In a clean environment at 25℃ and 50% humidity, weigh 12kg of CremophorRH40, 10kg of (polyethylene glycol-400) and 8kg of propylene glycol, with a dispensing error of ≤±0.1%;

[0151] ②Preliminary mixing: Add the above raw materials to a stainless steel mixing container under nitrogen protection and stir at 250 rpm for 12 minutes to achieve preliminary dispersion;

[0152] ③Sealed emulsification: Food-grade nitrogen (99.95% purity) is continuously introduced and emulsified at 400 rpm for 75 minutes under light-protected conditions to form a uniform and transparent oily concentrate. This concentrate can release fat-soluble active ingredients in intestinal fluid and form an easily dispersible emulsion.

[0153] ④ Stability pre-test: The concentrate was left to stand at 25℃ for 30 days. If no stratification, precipitation, or discoloration was observed, the stability was qualified.

[0154] ⑤ Targeted performance verification: Gastric juice stability test: 1 mL of concentrate was added to 9 mL of simulated gastric juice (pH 1.2), stirred at 37℃ and 100 rpm for 2 hours. The system remained stable and no microemulsion formed. Intestinal juice microemulsion formation test: 1 mL of concentrate was added to 9 mL of simulated intestinal juice (pH 6.8), stirred at 37℃ and 50 rpm. A uniform microemulsion with an average particle size of 72 nm was formed within 1.3 minutes. Release efficiency test: Using the dialysis bag method, the cumulative release of nervonic acid within 8 hours was 88.6%, which met the requirements. Dispersion performance test: 1 mL of microemulsion was added to 9 mL of simulated beverage matrix, stirred at room temperature for 30 seconds. A uniformly dispersed system was formed without stratification.

[0155] Capsule preparation

[0156] ① Ingredient dissolution: Mix 60kg of gelatin, 20kg of glycerin, 15kg of water and 5kg of dietary fiber, add to a constant temperature stirring tank, stir at 65℃ for 25 minutes until completely dissolved to form a uniform and transparent gel solution.

[0157] ② Anti-corrosion treatment: Add 0.2 kg of potassium sorbate to the adhesive solution and continue stirring for 8 minutes to ensure uniform dispersion;

[0158] ③ Vacuum degassing: Transfer the adhesive to a vacuum degassing tank and degas for 18 minutes at a pressure of -0.085MPa to completely remove air bubbles;

[0159] ④ Low-temperature spreading and setting: The temperature of the adhesive solution is controlled at 15℃ by a semiconductor cooling system. The film is spread into a film at a speed of 0.8m / min using a continuous spreader. The film thickness deviation is monitored by an online thickness detector and is ±0.015mm. The film is set by standing at room temperature for 12 minutes.

[0160] (3) Capsule forming

[0161] ① Content preparation: Mix 30kg of qualified self-microemulsifying concentrate with 60kg of low-temperature pressed Xanthoceras sorbifolium oil and 10kg of purified nervonic acid from Xanthoceras sorbifolium. Stir at 300rpm for 20 minutes at 23℃ until the mixture is homogeneous. This content can efficiently release fat-soluble active ingredients in intestinal fluid.

[0162] ② Quantitative injection: High-precision injection equipment is used to accurately inject 0.4g / particle between the capsule shell membranes, with an injection error of ≤±0.01g;

[0163] ③ Radio frequency sealing: In an environment of 23℃ and 50% humidity, a 13.56MHz radio frequency sealing device (power 3kW, sealing time 3 seconds) was used for molding, and the leakage rate was detected to be 0.08%.

[0164] ④ Intelligent drying: Microwave drying technology is used, with a drying temperature of 35℃ and a drying time of 2.5 hours (55% shorter than traditional hot air drying), controlling the final moisture content of the capsules to 9.2%, with a moisture uniformity deviation of ±0.3%.

[0165] (4) Quality Inspection and Packaging

[0166] ① AI visual quality inspection: Using an AI vision system with a detection accuracy of 0.01mm, 10,000 capsules were inspected, and 8 capsules with appearance defects were rejected, resulting in a quality inspection pass rate of 99.92%.

[0167] ② Process parameter verification: The viscosity of the adhesive solution was 185 cP (25℃), the particle size of the contents was 73 nm, the thickness of the capsule shell was 1.0 mm, and the moisture content was 9.0%. All parameters were monitored by the PAT system. The deviation of all parameters was ≤ ±5 nm, which met the requirements.

[0168] ③ Finished product testing: Randomly select 20 finished products and test the microemulsion formation time (1.2-1.4 minutes), average particle size (68-75 nm), nervonic acid release (86.2%-89.5%), capsule disintegration time (22-28 minutes), lipid-soluble component release efficiency (≥90%), and good water dispersion performance. If all indicators are qualified, the product is packaged and put into storage.

[0169] Example 2: Preparation of plant-based capsule shell intestinal microemulsion targeted release type Xanthoceras sorbifolium oil soft capsules

[0170] Raw material ratio (mass percentage): 70% cold-pressed Xanthoceras sorbifolium oil (nervonic acid content 3.8%), 15% polysorbate-80 (surfactant), 12% propylene glycol (co-surfactant), 3% oil body rich in Xanthoceras sorbifolium glycosides (content 18%); Capsule material: 70% hydroxypropyl methylcellulose plant rubber, 18% glycerin, 12% water; Preservative: 0.15% sodium dehydroacetate (based on total mass of capsule material).

[0171] Preparation steps:

[0172] (1) Preparation of self-microemulsion delivery system: Ingredients were prepared at 22℃. 15kg of (polysorbate-80) and 12kg of propylene glycol were initially mixed for 10 minutes. Under nitrogen protection, the mixture was stirred and emulsified at 350rpm for 60 minutes. After the stability test was qualified, the targeting performance verification showed that it was stable in gastric juice and formed a microemulsion with an average particle size of 65nm in intestinal juice in 1.1 minutes. The nervonic acid release was 87.3%. The dispersion performance test met the requirements for water-based food additives.

[0173] (2) Capsule preparation: 70 kg of hydroxypropyl methylcellulose, 18 kg of glycerol and 12 kg of water were mixed and stirred at 60°C for 20 minutes to dissolve. 0.15 kg of sodium dehydroacetate was added and stirred for 5 minutes. Vacuum degassing was performed at -0.08 MPa for 15 minutes. Low temperature spreading was carried out at 10°C (0.5 m / min). The film thickness deviation was ±0.01 mm. The film was allowed to stand at room temperature for 10 minutes to set.

[0174] (3) Capsule forming: The contents are filled at 0.3g / capsule, sealed with 27.12MHz radio frequency (power 2kW, sealing time 2 seconds) in an environment of 20℃ and 40% humidity, dried with infrared at 30℃ for 2 hours, and the final moisture content is 8.5%.

[0175] (4) Quality inspection: The pass rate of AI vision quality inspection is 99.95%, the monitoring parameters of PAT system all meet the requirements, the absorption efficiency of nervonic acid in finished product is 62.3%, and the release efficiency of fat-soluble components is ≥88%.

[0176] Example 3: Preparation of high-content, optional ingredient, intestinal microemulsion-targeted release type Xanthoceras sorbifolium oil soft capsules

[0177] Raw material ratio (mass percentage): 50% low-temperature pressed Xanthoceras sorbifolium oil (nervonic acid content 3.5%), 18% (Cremophor-RH40), 12% (polyethylene glycol-400), 10% purified nervonic acid from Xanthoceras sorbifolium (purity 93%); Capsule material: 65% seaweed polysaccharide-based gelatin, 20% glycerin, 15% water; Preservative: 0.3% potassium sorbate (based on total mass of capsule material).

[0178] Preparation steps: (1) Preparation of self-microemulsion delivery system: Ingredients were prepared at 28℃. 18kg of (Cremophor RH40) and 12kg of (polyethylene glycol-400) were initially mixed for 15 minutes. Under nitrogen protection, the mixture was stirred and emulsified at 500rpm for 90 minutes. After the stability test was qualified, the targeting performance verification showed that a microemulsion with an average particle size of 78nm was formed in the intestinal fluid in 1.5 minutes. The release of nervonic acid was 85.7%, and the water dispersion performance was good.

[0179] (2) Capsule preparation: 65 kg of seaweed polysaccharide-based gel, 20 kg of glycerol and 15 kg of water were mixed and stirred at 70°C for 30 minutes to dissolve. 0.3 kg of potassium sorbate was added and stirred for 10 minutes. Vacuum degassing was performed at -0.09 MPa for 20 minutes. Low temperature spreading was carried out at 20°C (1.0 m / min). The film thickness deviation was ±0.02 mm. The film was allowed to stand at room temperature for 15 minutes to set.

[0180] (3) Capsule forming: The contents are filled at 0.5g / capsule, sealed with 13.56MHz radio frequency in an environment of 25℃ and 60% humidity (power 5kW, sealing time 5 seconds), dried at terahertz wave temperature of 40℃ for 3 hours, and the final moisture content is 9.8%.

[0181] (4) Quality inspection: The pass rate of AI visual quality inspection is 99.90%, the monitoring parameters of PAT system meet the requirements, the absorption efficiency of nervonic acid in finished product is 65.1%, and the release efficiency of fat-soluble components is ≥91%.

[0182] Industrial applicability of the invention

[0183] The intestinal microemulsion targeted release type *Sapindus mukorossi* oil soft capsules and their preparation method of the present invention have significant industrial applicability, specifically reflected in:

[0184] 1. Raw materials are readily available and compliant: All raw materials (low-temperature pressed Xanthoceras sorbifolium oil, surfactants, capsule materials, preservatives, etc.) are food-grade compliant products, meeting the requirements of relevant regulations such as GB2716-2018 "National Food Safety Standard for Vegetable Oils" and GB2760-2024 "Standard for the Use of Food Additives". The raw materials are widely available, the procurement cost is controllable, and there are no scarce or restricted ingredients.

[0185] 2. The process is compatible with existing production lines: The core steps of the preparation process (ingredient preparation, emulsification, shell forming, capsule filling, and drying) are consistent with the existing soft capsule production line. Only the sealing process needs to be modified by radio frequency module, and a new process analysis sensor and AI vision quality inspection system need to be added. The modification cost is low and the cycle is short (usually 1-3 months to complete), and there is no need to rebuild the production line.

[0186] 3. High production efficiency and controllable cost: Intelligent directional drying technology (infrared, microwave, terahertz wave) shortens the drying cycle by more than 50% compared to traditional hot air drying. The AI ​​visual quality inspection system replaces manual inspection, improving inspection efficiency by more than 10 times, significantly reducing labor costs and production cycle. When produced on a large scale, the unit product cost only increases by 15%-20% compared to ordinary Sapindus mukorossi oil capsules, making it competitive in the market.

[0187] 4. High quality control and high pass rate: The whole process analysis technology (PAT) monitors key parameters such as adhesive viscosity, content particle size, shell thickness, and moisture content in real time. The deviation of key indicators is ≤±5nm, and the difference between product batches is small. The AI ​​vision quality inspection system realizes 100% online detection of appearance defects, and the finished product pass rate is ≥99%, which meets the quality control requirements of large-scale production.

[0188] 5. Broad Market Application Prospects: The product addresses the core pain points of ordinary Xanthoceras sorbifolium oil, namely low absorption efficiency and limited application scenarios. Through emulsification technology, it achieves efficient release of fat-soluble active ingredients and can be transformed into an easily dispersed emulsion form, suitable for the addition needs of water-based foods such as beverages and yogurt, further expanding its application scenarios. The product can be applied to functional food fields such as nourishing nerves, improving memory, and maintaining brain health, with target consumer groups covering the middle-aged and elderly, mental workers, students preparing for exams, and people recovering from surgery, resulting in strong market demand. At the same time, the technical solution of this invention can be extended to the development of high-value formulations of other plant-derived functional oils such as flaxseed oil and walnut oil, demonstrating good technological radiating potential.

[0189] In summary, this invention, through its pioneering "intestinal microemulsification targeted release" technology system, integrates three core technologies—precise intestinal targeted delivery, controllable soft capsule disintegration, and efficient in-situ intestinal emulsification—to form a synergistic effect. This achieves efficient release of fat-soluble active ingredients and broadens application scenarios, constructing an integrated solution encompassing formulation, process, and quality control. It realizes the high-value upgrade of Xanthoceras sorbifolium oil, significantly improving the bioavailability of active ingredients and the precision and reliability of nutritional intervention. The technology is advanced, highly industrially applicable, and has the conditions for large-scale industrial production. At the same time, it provides a replicable technical paradigm for the formulation development of similar functional oils, possessing significant economic and social value.

[0190] Compared with common *Sapindus mukorossi* oil and existing related technologies, this invention has the following significant and inventive advantages:

[0191] 1. A qualitative leap in absorption efficiency: Through intestinal microemulsion targeted release technology, the absorption efficiency of nervonic acid is increased from <20% of ordinary Xanthoceras sorbifolium oil to ≥60%, the targeted release efficiency is ≥3.5 times that of ordinary Xanthoceras sorbifolium oil, and the utilization rate of effective ingredients is increased by more than 3 times. This completely solves the core pain point of low absorption efficiency of ordinary Xanthoceras sorbifolium oil, allowing the high-value nervonic acid function of Xanthoceras sorbifolium oil to be fully utilized.

[0192] 2. Precise and controllable targeted release: The technical definition and quantitative indicators of "intestinal microemulsion targeted release" are clearly defined. The microemulsion delivery system and the adaptable capsule work synergistically to achieve a precise targeting effect of "stable gastric juice and rapid intestinal juice triggering". The microemulsion formation time is ≤1.5 minutes, the particle size is ≤80nm and the distribution is uniform. The cumulative release of nervonic acid is ≥85%, which is not affected by individual physiological differences. The product efficacy stability is significantly better than existing technologies.

[0193] 3. The performance of the capsule shell is well-suited to the target system: The standardized capsule shell preparation process ensures uniform capsule shell thickness (deviation ≤ ±0.02mm) and controllable gastrointestinal fluid disintegration characteristics (no disintegration in gastric fluid for 2 hours, complete disintegration in intestinal fluid for 15-30 minutes) through key steps such as precise temperature control, vacuum degassing, and online film thickness monitoring. This effectively avoids premature or delayed release of contents and ensures batch consistency of the targeting effect.

[0194] 4. Significantly enhanced stability of active ingredients: The entire process is protected by low temperature (pressing, emulsification, and molding temperatures are all ≤70℃), nitrogen-protected emulsification, and radio frequency sealing processes, which effectively isolate the damage of light, heat, and oxygen to nervonic acid and polyunsaturated fatty acids. After 12 months of storage, the nervonic acid retention rate is >92%, which is far higher than the level of less than 70% of ordinary Sapindus mukorossi oil, significantly extending the product's shelf life and efficacy stability.

[0195] 5. Superior in both food safety and user experience: The total amount of surfactants and co-surfactants is strictly controlled to be lower than that of Xanthoceras sorbifolium oil, avoiding intestinal irritation caused by excessive emulsifiers; at the same time, the nano-sized microemulsion can be fully absorbed by the intestines, with extremely low unabsorbed oil residue, reducing the incidence of intestinal discomfort (bloating, flatulence, etc.) to below 5%, which is significantly better than ordinary Xanthoceras sorbifolium oil (more than 32%), thus improving the user's consumption experience.

[0196] 6. Intelligent and full-process quality control system: The process analysis technology (PAT) is used to monitor core parameters such as adhesive viscosity, content particle size, and shell thickness in real time. Combined with the AI ​​vision quality inspection system, appearance defects are automatically eliminated. The deviation of key indicators is ≤±5nm, and the product qualification rate is ≥99%, which solves the problem of existing technologies relying on manual inspection and poor quality consistency.

[0197] 7. Strong industrial adaptability and low transformation threshold: The preparation process can be adapted and modified to existing soft capsule production lines, requiring only the addition of radio frequency sealing modules, online sensors, and AI quality inspection systems. No dedicated core equipment needs to be purchased, resulting in low modification costs and short cycles. Intelligent drying technology improves production efficiency by more than 50% compared to traditional processes and reduces labor costs by 30%, meeting the needs of large-scale production. 8. High-value upgrade of product form: For the first time, *Xanthoceras sorbifolium* oil is upgraded from a traditional edible oil form to a functional preparation that precisely delivers nervonic acid, expanding its application scenarios in functional foods such as those that nourish nerves and improve memory. The target consumer groups cover the elderly, mental workers, and post-operative recovery groups, providing a new technical path for the high-value development of *Xanthoceras sorbifolium* oil, with broad market application prospects.

Claims

1. A type of intestinal microemulsion targeted release Xanthoceras sorbifolium oil soft capsule, characterized in that, The product comprises a capsule and its contents. The contents consist of 40%-70% by mass of low-temperature pressed Xanthoceras sorbifolium oil (pressing temperature ≤60℃, acid value ≤1.5mg KOH / g), 20%-50% by mass of a self-microemulsifying delivery system, and 0%-10% by mass of optional components. The self-microemulsifying delivery system is composed of a surfactant and a co-surfactant in a mass ratio of 1:0.9-1:1.1, with the total mass of the surfactant and co-surfactant being 40%-80% of the mass of the Xanthoceras sorbifolium oil. The contents remain physically stable and do not emulsify within 2 hours in simulated gastric fluid (pH 1.2, 37℃), and spontaneously form uniform nanoscale microemulsions with an average particle size of 50-80nm within 1.5 minutes in simulated intestinal fluid (pH 6.8, 37℃). The absolute value of the zeta potential of the microemulsion is ≥25mV. It remains stable in intestinal fluid for ≥24 hours without stratification or precipitation, and the cumulative release of nervonic acid in the intestine is ≥85%.

2. The soft capsule according to claim 1, characterized in that, The surfactant is a compound of polysorbate-80 and Cremophor RH40 in a mass ratio of 1:0.5 to 1:1.5; the co-surfactant is a compound of polyethylene glycol-400 and propylene glycol in a mass ratio of 1:0.8 to 1:1.

2.

3. The soft capsule according to claim 1, characterized in that, The optional ingredient is nervonic acid of Xanthoceras sorbifolium with a purity of ≥95% or oil body of Xanthoceras sorbifolium shell extract with a content of ≥20%, and the mass ratio of the optional ingredient to Xanthoceras sorbifolium oil is ≤1:

5.

4. The soft capsule according to claim 1, characterized in that, The capsule shell is a hydroxypropyl methylcellulose plant gel containing 5%-8% by weight collagen and 10%-12% by weight dietary fiber. The capsule shell is 0.9-1.1 mm thick and has a final moisture content of 8.5%-9.5%. It has a disintegration rate of ≤5% in simulated gastric juice (pH 1.2, 37℃) after 2 hours and complete disintegration in simulated intestinal juice (pH 6.8, 37℃) after 20-25 minutes.

5. A method for preparing a soft capsule as described in any one of claims 1-4, characterized in that, Includes the following steps: (1) Preparation of self-microemulsion delivery system: Weigh the surfactant and co-surfactant at 22-26℃, mix them initially for 12-14 minutes under nitrogen protection, and then emulsify them at 350-450 rpm for 70-80 minutes under nitrogen atmosphere and light-proof sealed conditions to form a homogeneous transparent oily concentrate. After passing the stability test and targeting performance verification, it is ready for use. (2) Capsule preparation: Mix the capsule materials according to the proportion, add 3.5-4.5 times the mass of deionized water, stir and dissolve at 63-67℃ for 23-27 minutes until the light transmittance is ≥95%, add 0.15%-0.25% mass percentage of preservative, continue stirring for 7-9 minutes, vacuum degas at -0.085~-0.088MPa for 17-19 minutes, control the temperature of the adhesive solution at 13-17℃, spread it into a film at a speed of 0.6-0.8m / min (film thickness deviation ≤±0.01mm), and let it stand at room temperature for 12-14 minutes to set; (3) Capsule formation: The concentrated liquid from step (1) is mixed evenly with the *Sapindus mukorossi* oil and optional ingredients at 20-22℃, and injected quantitatively into the capsule shell membrane at 0.35-0.45g / capsule. The capsule is formed in an environment of 22-24℃ and 45%-55% humidity using a 13.56MHz radio frequency sealing device (power 3-4kW, sealing time 2-4 seconds), and then subjected to intelligent directional drying at 33-37℃. (4) Quality inspection and packaging: Defective products are removed by an AI vision quality inspection system with an inspection accuracy of ≤0.01mm. After the process parameters are reviewed and the sampling inspection is qualified, the products are packaged and put into storage under nitrogen protection.

6. The preparation method according to claim 5, characterized in that, In step (1), the stability test was conducted by standing for 30 days at 25°C and 60% ± 5% relative humidity. The concentrate showed no stratification, precipitation, or color change. The target performance verification included gastric fluid stability test (stirring at 100 rpm for 2 hours in simulated gastric fluid at 37°C and pH 1.2, with a system particle size change rate ≤ 5%), intestinal fluid microemulsion formation test, and release efficiency test.

7. The preparation method according to claim 5, characterized in that, In step (2), the preservative is a mixture of potassium sorbate and sodium dehydroacetate in a mass ratio of 1:1; when spreading the film, an online thickness monitoring system is used to adjust it in real time, and the film thickness uniformity is ≥98%.

8. The preparation method according to claim 5, characterized in that, In step (3), intelligent directional drying adopts microwave-infrared composite drying technology with a drying power gradient of 1-1.5kW (first 10 minutes) and 0.8-1kW (last 20 minutes). After drying, the moisture uniformity deviation of the capsules is ≤±0.3%.

9. The preparation method according to claim 5, characterized in that, The preparation process employs process analysis technology (PAT) to monitor key parameters in real time. These key parameters include the viscosity of the adhesive (180-220 cP, 25℃), the particle size of the contents (50-80 nm, with a control accuracy of ±2 nm), the thickness of the capsule shell, and the moisture content during the drying process. Each batch has ≥150 detection points, and the deviation of the targeting performance verification data is ≤±3 nm.

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