Seabuckthorn seed oil and fruit oil double-effect capsule-in-capsule capsule and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and discloses a double-effect capsule-in-capsule capsule of seabuckthorn seed oil and fruit oil and a preparation method of the double-effect capsule-in-capsule capsule of the seabuckthorn seed oil and the fruit oil, the double-effect capsule-in-capsule capsule of the seabuckthorn seed oil and the fruit oil comprises an inner capsule and an outer capsule, the inner capsule contains the seabuckthorn seed oil, the outer capsule contains the seabuckthorn fruit oil, and the mass ratio of the seabuckthorn seed oil to the seabuckthorn fruit oil is 1: 9-3: 7; the sea buckthorn seed oil contains 50%-70% of linoleic acid, 10%-30% of linolenic acid and 5%-15% of oleic acid; the sea buckthorn fruit oil contains 20%-40% of palmitoleic acid, 20%-40% of oleic acid and 50-300 mg / kg of carotenoid; the inner capsule shell is composed of gelatin, glycerin and purified water; the outer capsule shell is composed of gelatin, glycerin, purified water and food coloring. Through an original bag-in-bag space partition structure, the sea buckthorn seed oil with relatively active chemical properties is encapsulated in the inner bag, and then the sea buckthorn fruit oil is placed in the outer bag, so that effective physical isolation of two kinds of functional grease is realized.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, specifically to a dual-effect capsule of sea buckthorn seed oil and fruit oil and its preparation method. Background Technology

[0002] Sea buckthorn, a plant resource with both medicinal and edible uses, has garnered widespread attention due to its unique nutritional components and health benefits. Two oils with distinct properties and effects can be extracted from sea buckthorn: sea buckthorn fruit oil and sea buckthorn seed oil. Sea buckthorn fruit oil, primarily extracted from the pulp, is rich in palmitic acid and carotenoids, playing a positive role in protecting mucous membranes and repairing tissues. Sea buckthorn seed oil, pressed from the seeds, mainly consists of polyunsaturated fatty acids such as linoleic acid and linolenic acid, which are important for regulating the body's internal functions. To facilitate consumer intake and maximize the combined health benefits of these two oils, their formulation into soft capsules and other similar forms is currently the mainstream approach in the market.

[0003] In existing technologies, to achieve the combination of two oils, a common approach is to directly and physically mix sea buckthorn fruit oil and sea buckthorn seed oil in a certain proportion, and then fill the mixture into a single capsule. However, this simple preparation method has inherent drawbacks that are difficult to overcome. The high content of polyunsaturated fatty acids in sea buckthorn seed oil is chemically extremely unstable. When coexisting with the complex composition of sea buckthorn fruit oil and the oxygen inevitably encountered during processing and storage, it is highly susceptible to oxidative rancidity, leading to a rapid increase in the product's peroxide value and acid value. This not only degrades the product's flavor and quality but, more seriously, degrades and renders the active ingredients ineffective, and may even produce substances harmful to the human body.

[0004] Furthermore, this type of single-chamber capsule, which simply mixes two oils, releases its contents simultaneously within the body, failing to differentiate based on the different functional properties and optimal sites of action of the two oils. Ideally, the sea buckthorn fruit oil should act first, followed by the absorption of the sea buckthorn seed oil. However, in traditional mixed capsules, both oils are released simultaneously upon dissolving in the stomach, failing to achieve a programmed synergistic effect and significantly diminishing the overall efficacy, thus failing to fully realize the potential of the combined oils. Simultaneously, the high-temperature drying processes used in conventional capsule manufacturing to improve production efficiency can cause irreversible damage to valuable heat-sensitive active substances in sea buckthorn oil, such as vitamin E and carotenoids, further reducing the actual nutritional value of the final product.

[0005] Therefore, how to effectively solve the stability problem of mixing two functional oils and achieve their programmed release in vivo to maximize synergistic effects, while fully protecting their natural active ingredients during the production process, is a technical challenge that urgently needs to be solved in this field. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a dual-effect capsule of sea buckthorn seed oil and fruit oil and its preparation method, which solves the problems of poor stability after mixing sea buckthorn fruit oil and seed oil, inability to achieve programmed synergistic release, and easy loss of active ingredients during the preparation process in existing technologies.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a dual-effect capsule containing sea buckthorn seed oil and fruit oil, comprising: The inner capsule contains sea buckthorn seed oil and the outer capsule contains sea buckthorn fruit oil, wherein the mass ratio of sea buckthorn seed oil to sea buckthorn fruit oil is 1:9 to 3:7. The sea buckthorn seed oil contains 50%–70% linoleic acid, 10%–30% linolenic acid, and 5%–15% oleic acid. The sea buckthorn fruit oil contains 20%–40% palmitoleic acid, 20%–40% oleic acid, and 0.005%–0.03% carotenoids. The inner capsule shell is composed of gelatin, glycerin, and purified water; The outer capsule shell is composed of gelatin, glycerin, purified water and food coloring.

[0008] Preferably, the content of sea buckthorn seed oil in the inner capsule is 100-300 mg, and the content of sea buckthorn fruit oil in the outer capsule is 200-500 mg.

[0009] Preferably, both the inner capsule and the outer capsule are soft capsule structures, with the inner capsule completely embedded inside the outer capsule, forming a capsule-within-a-capsule structure.

[0010] Preferably, the capsule shell contains a natural antioxidant selected from vitamin E, tea polyphenols, or rosemary extract to improve stability.

[0011] Preferably, the sea buckthorn seed oil and sea buckthorn fruit oil are obtained by supercritical CO2 extraction.

[0012] A method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil includes the following steps: S1. Extract sea buckthorn seed oil and sea buckthorn fruit oil separately; S2. Seabuckthorn seed oil is filled into the inner capsule shell material to prepare the inner capsule; S3. Place the inner capsule in the outer capsule forming mold and inject a mixture of sea buckthorn fruit oil and outer capsule shell material to form an outer capsule, thus obtaining a capsule-within-a-capsule structure. S4. Dry and shape to obtain capsules within capsules.

[0013] Preferably, in step S1, the sea buckthorn seed oil and sea buckthorn fruit oil are extracted using supercritical CO2 fluid extraction at an extraction temperature of 35–50°C and a pressure of 25–35 MPa.

[0014] Preferably, the inner bladder is formed using the droplet method or the drum droplet method, and the outer bladder is formed using the rotary molding method or the plunger filling method.

[0015] Preferably, in step S4, the drying process adopts constant temperature forced air drying, with a temperature of 20-30°C and a time of 24-48 hours.

[0016] Preferably, vitamin E or rosemary extract is added to the capsule material to improve the antioxidant stability and shelf life of the product.

[0017] This invention provides a dual-effect capsule of sea buckthorn seed oil and fruit oil, and its preparation method. It has the following beneficial effects: 1. This invention utilizes a unique capsule-within-a-capsule spatial partitioning structure to encapsulate the chemically reactive sea buckthorn seed oil in the inner capsule and place the sea buckthorn fruit oil in the outer capsule. This achieves effective physical isolation between the two functional oils, blocking the contact between unstable components and external oxygen and other components, greatly delaying the occurrence of oxidative rancidity, thereby improving the chemical stability of the product and ensuring the quality and safety of the product within its shelf life.

[0018] 2. In this invention, the contents of the outer capsule are designed to be preferentially released in the gastric environment, while the inner capsule can resist gastric acid and release its contents only after entering the intestinal environment. This phased targeted release mode allows the two types of oils to perform their respective biological functions in the most suitable physiological sites, thereby achieving a synergistic effect of first nourishing and then absorbing.

[0019] 3. The preparation method of the present invention specifically includes a mild low-temperature drying process. This process can effectively avoid the damage to the valuable heat-sensitive active ingredients in sea buckthorn oil caused by traditional high-temperature drying. Through this refined control of the processing, the natural bioactivity and nutritional value of the raw materials are preserved to the greatest extent, ensuring that the final product has higher quality and stronger efficacy.

[0020] 4. In this invention, the sea buckthorn fruit oil in the outer capsule not only exerts its own effects, but also constitutes a natural antioxidant microenvironment, which further enhances the protection of the sea buckthorn seed oil in the inner capsule. This intrinsic synergistic effect between components ensures that the final product has higher overall quality and efficacy, surpassing the effect of simple physical isolation, and achieving synergistic protection between components.

[0021] 5. This invention organically integrates two types of sea buckthorn oils with different effects, providing a more comprehensive health solution. By first releasing the fruit oil to nourish specific parts, and then releasing the seed oil for deep nutritional supplementation, a complete functional chain of step-by-step conditioning and multiple benefits is formed, which enhances the product's function from a single nutritional supplement to a synergistic systemic solution, thus broadening the product's application value. Attached Figure Description

[0022] Figure 1 This is a flowchart illustrating the preparation process of the present invention. Detailed Implementation

[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] Example 1: This example provides a method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil according to the present invention.

[0025] Step S1: Preparation of sea buckthorn seed oil and sea buckthorn fruit oil Supercritical CO2 fluid extraction technology was used to extract oils from sea buckthorn seeds and sea buckthorn pulp, respectively. The extraction process parameters were set as follows: extraction temperature 40℃ and extraction pressure 30 MPa. The crude oil obtained from the extraction was then refined through degumming, deacidification, decolorization, and deodorization processes to obtain high-purity sea buckthorn seed oil and sea buckthorn fruit oil for later use.

[0026] Step S2: Preparation of the inner capsule Preparation of capsule shell material: Weigh 10.0 kg of gelatin, 5.0 kg of glycerin and 10.0 kg of purified water, place them in a gelatin dissolving tank, heat to 65℃ and stir to fully dissolve and homogenize them to obtain the inner capsule shell solution.

[0027] Contents: Weigh 20.0 kg of the refined sea buckthorn seed oil obtained in step S1.

[0028] Compression molding: Using the rotary drum dripping method, sea buckthorn seed oil is encapsulated with the above-mentioned capsule solution to produce spherical inner capsules with a single capsule content of 200 mg.

[0029] Step S3: Preparation of the outer capsule (capsule within a capsule) Preparation of capsule shell material: Weigh 30.0 kg of gelatin, 15.0 kg of glycerin, 30.0 kg of purified water and an appropriate amount of lemon yellow food coloring, place them in a gelatin dissolving tank, heat to 65℃ and stir to fully dissolve and homogenize them to obtain the outer capsule shell solution.

[0030] Contents preparation: Weigh 60.0 kg of the refined sea buckthorn fruit oil obtained in step S1, and add 0.3 kg of vitamin E as an antioxidant, and stir well.

[0031] Encapsulation and molding: The outer capsule is prepared using a rotary molding method. The inner capsule obtained in step S2 is placed into the hopper of a soft capsule press, and positioned into the cavity of the outer capsule molding die using a positioning device. Simultaneously, the prepared sea buckthorn fruit oil contents and the outer capsule shell solution are injected, and the capsule is pressed to obtain a capsule-in-capsule wet capsule. Each outer capsule contains 600mg of sea buckthorn fruit oil.

[0032] Step S4: Drying and Shaping The prepared capsule-in-capsule wet capsules were placed in a constant temperature forced-air drying oven at 25°C and 50% relative humidity for 36 hours. The finished product was then obtained. The inner capsule contained 200 mg of seed oil, and the outer capsule contained 450 mg of fruit oil.

[0033] Example 2: This example provides a method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil according to the present invention.

[0034] Step S1: Preparation of sea buckthorn seed oil and sea buckthorn fruit oil Supercritical CO2 fluid extraction technology was employed, with the extraction process parameters set as follows: extraction temperature 35℃ and extraction pressure 25MPa. The extract was then refined for later use.

[0035] Step S2: Preparation of the inner capsule Preparation of capsule shell materials: Weigh 6.0 kg of gelatin, 3.0 kg of glycerin and 6.0 kg of purified water, and heat to 60℃ to prepare capsule shell solution.

[0036] Contents: Weigh out 10.0 kg of refined sea buckthorn seed oil.

[0037] Compression molding: Using the droplet method, sea buckthorn seed oil is encapsulated with the above-mentioned capsule solution to produce inner capsules with a single capsule content of 100 mg.

[0038] Step S3: Preparation of the outer capsule (capsule within a capsule) Preparation of capsule shell materials: Weigh 20.0 kg of gelatin, 10.0 kg of glycerin and 20.0 kg of purified water, and heat to 60℃ to prepare capsule shell solution.

[0039] Contents preparation: Weigh 40.0 kg of refined sea buckthorn fruit oil and add 0.2 kg of tea polyphenols as an antioxidant, then stir well.

[0040] Encapsulation and molding: The outer capsule was prepared using a plunger-filling method. The inner capsule was placed in a mold, and the contents of sea buckthorn fruit oil and the outer capsule shell solution were injected, followed by encapsulation and molding. Each outer capsule contained 400 mg of sea buckthorn fruit oil.

[0041] Step S4: Drying and Shaping The wet capsules were placed in a constant temperature forced-air drying oven at 20°C and 40% relative humidity for 24 hours to obtain the finished product. The final product contained 100 mg of seed oil in the inner capsule and 400 mg of fruit oil in the outer capsule, with a mass ratio of 1:4.

[0042] Example 3: This example provides a method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil according to the present invention.

[0043] Step S1: Preparation of sea buckthorn seed oil and sea buckthorn fruit oil Supercritical CO2 fluid extraction technology was employed, with the extraction process parameters set as follows: extraction temperature 50℃ and extraction pressure 35MPa. The extract was then refined for later use.

[0044] Step S2: Preparation of the inner capsule Preparation of capsule shell materials: Weigh 12.0 kg of gelatin, 6.0 kg of glycerin and 12.0 kg of purified water, and heat to 70°C to prepare capsule shell solution.

[0045] Contents: Weigh out 21.0 kg of refined sea buckthorn seed oil.

[0046] Compression molding: Using the rotary drum dripping method, sea buckthorn seed oil is encapsulated with the above-mentioned capsule solution to produce inner capsules with a single capsule content of 210 mg.

[0047] Step S3: Preparation of the outer capsule (capsule within a capsule) Preparation of capsule shell materials: Weigh 35.0 kg of gelatin, 18.0 kg of glycerin, 35.0 kg of purified water and an appropriate amount of Sunset Yellow food coloring, and heat to 70°C to prepare capsule shell solution.

[0048] Contents preparation: Weigh 49.0 kg of refined sea buckthorn fruit oil and add 0.25 kg of rosemary extract as an antioxidant, and stir well.

[0049] Encapsulation and molding: The outer capsule is prepared using a rotational molding method. The inner capsule is placed in a mold, and the contents of sea buckthorn fruit oil and the outer capsule shell solution are injected, followed by encapsulation and molding. Each outer capsule contains 490 mg of sea buckthorn fruit oil.

[0050] Step S4: Drying and Shaping The wet capsules were placed in a constant temperature forced-air drying oven at 30°C and 60% relative humidity for 48 hours to obtain the finished product. The final product contained 210 mg of seed oil in the inner capsule and 490 mg of fruit oil in the outer capsule, with a mass ratio of 3:7.

[0051] Comparative Example 1: Compared to Example 1, the difference is that this comparative example does not use a capsule-within-a-capsule structure. Instead, 20.0 kg of sea buckthorn seed oil and 60.0 kg of sea buckthorn fruit oil from Example 1 are directly physically mixed, and the outer capsule shell material and preparation process of Example 1 are used to prepare a single-cavity ordinary soft capsule. All other aspects are the same.

[0052] Comparative Example 2: Compared to Example 1, the difference lies in that the mass ratio of sea buckthorn seed oil to sea buckthorn fruit oil in this comparative example is adjusted to 1:19, that is, 5.0 kg of sea buckthorn seed oil is used to prepare the inner capsule, and 95.0 kg of sea buckthorn fruit oil is used as the outer capsule contents. All other aspects are the same.

[0053] Comparative Example 3: Compared to Example 1, the difference lies in that the mass ratio of sea buckthorn seed oil to sea buckthorn fruit oil in this comparative example is adjusted to 1:1, that is, 40.0 kg of sea buckthorn seed oil is used to prepare the inner capsule, and 40.0 kg of sea buckthorn fruit oil is used as the outer capsule contents. All other aspects are the same.

[0054] Comparative Example 4: Compared to Example 1, the difference is that the inner capsule contents of this comparative example are not filled with sea buckthorn seed oil, but with an equal amount of sea buckthorn fruit oil. That is, both the inner and outer capsule contents are filled with sea buckthorn fruit oil, in order to verify the necessity of the synergistic effect of the two oils. Everything else is the same.

[0055] Comparative Example 5: Compared to Example 1, the difference lies in that the drying process in step S4 uses conventional high-temperature rapid drying, that is, the temperature is raised to 60°C and the drying time is shortened to 8 hours, to verify the superiority of the low-temperature mild drying process used in this invention. All other steps are the same.

[0056] Test Example 1: Experimental Objective This test aims to compare the chemical stability of Example 1 (capsule-in-capsule structure) and Comparative Example 1 (conventional mixed capsule) under long-term storage conditions under high temperature and high humidity through accelerated aging tests. Stability is evaluated by changes in key quality indicators—peroxide value and acid value.

[0057] 2. Experimental Samples Sample group A: Dual-effect capsules prepared according to the method of Example 1 of the present invention.

[0058] Sample group B: Mixed soft capsules prepared according to the method of Comparative Example 1.

[0059] 3. Experimental Instruments and Conditions Instruments: Constant temperature and humidity incubator, analytical balance, acid burette, and standard laboratory glassware.

[0060] Accelerated aging conditions: Temperature set at (40 ± 2)℃, relative humidity set at (75 ± 5)%.

[0061] 4. Experimental Procedure Initial state sampling (month 0): Sufficient capsules (approximately 20 capsules) were randomly selected from sample group A and sample group B, respectively.

[0062] Cut open each capsule one by one, carefully squeeze out all the contents into a clean, dry beaker, and mix well.

[0063] According to the methods in GB 5009.227-2016 National Food Safety Standard - Determination of Peroxide Value in Food and GB 5009.229-2016 National Food Safety Standard - Determination of Acid Value in Food, the initial peroxide value and acid value of the contents of the two groups of samples were determined and the data were recorded.

[0064] Accelerated aging treatment: Place the sealed sample group A and sample group B into a constant temperature and humidity incubator that has been preset with temperature and humidity, and start timing.

[0065] Periodic sampling and testing: After storing the samples in the incubator for 1 month, 3 months and 6 months respectively, take out appropriate amounts of the finished products from the constant temperature and humidity chamber for sample group A and sample group B.

[0066] Repeat step 1 to sample the contents of the sample at each time point and determine its peroxide value and acid value.

[0067] During each test, the contents of the oil were also sensorily evaluated, and the color and odor were recorded to see if there were any significant changes, especially whether a rancid smell (the distinctive odor of rancid oil) was produced.

[0068] The experimental results are shown in Table 1: Table 1 Comparison of changes in peroxide value and acid value during accelerated stability testing

[0069] As clearly shown in Table 1, the accelerated stability test data demonstrates that the dual-effect capsule-in-capsule provided by this invention exhibits excellent chemical stability under harsh conditions of high temperature and high humidity. After storage for up to 6 months, the measured increase in peroxide value and acid value is minimal, significantly better than traditional capsules made by directly mixing two types of oils. This result directly confirms the significant advantages of the technical solution of this invention in solving the problem of oxidative rancidity of oils.

[0070] The superior technical effects described above are fundamentally due to the unique capsule-within-a-capsule spatial compartmentalization structure of this invention. Sea buckthorn seed oil, rich in chemically active polyunsaturated fatty acids, is highly susceptible to oxidation and is the most unstable component in the entire product system. This invention pre-encapsulates the sea buckthorn seed oil within an independent inner capsule, utilizing the capsule's shell as a robust physical barrier to effectively isolate it completely from external oxygen and the complex components of the sea buckthorn fruit oil within the outer capsule. This physical isolation fundamentally blocks the oxidation chain reaction pathway that leads to increased peroxide value and acid value, thereby protecting the chemical integrity of the core active ingredient.

[0071] Therefore, the test results strongly demonstrate that the technical challenge of poor stability after mixing two functional oils has been successfully overcome through specific product structure design rather than chemical additives. This inherent stability brought about by structural innovation ensures that the product can maintain the effective content and natural quality of its active ingredients to the maximum extent throughout its shelf life, providing consumers with high-end sea buckthorn oil preparations that are more reliable in efficacy and more stable in quality.

[0072] Test Example 2: Experimental Objective This test aims to verify the programmed release characteristics of Example 1 (capsule-in-capsule structure) of the present invention through an in vitro dissolution test simulating the human gastrointestinal environment, and to compare it with the release behavior of Comparative Example 1 (traditional mixed capsule) to prove its synergistic release mechanism of releasing fruit oil first and then seed oil.

[0073] Experimental samples Sample group A: Dual-effect capsules prepared according to the method of Example 1 of the present invention.

[0074] Sample group B: Mixed soft capsules prepared according to the method of Comparative Example 1.

[0075] Experimental instruments and reagents Instruments: Intelligent dissolution tester (with automatic sampling system), high performance liquid chromatograph (HPLC), analytical balance, pH meter.

[0076] Reagents: hydrochloric acid, sodium chloride, pepsin (for preparing simulated gastric juice); potassium dihydrogen phosphate, sodium hydroxide, trypsin (for preparing simulated intestinal juice); palmitoleic acid standard, linoleic acid standard; chromatographic grade methanol, acetonitrile.

[0077] Experimental steps Establishment of chromatographic conditions: Establish a high-performance liquid chromatography (HPLC) method that can simultaneously or separately and accurately quantify representative components in the oil contents—palmitoleic acid (representing sea buckthorn fruit oil) and linoleic acid (representing sea buckthorn seed oil).

[0078] Dissolution test - simulated gastric stage: Six tablets of sample group A were placed into six dissolution cups containing 900 mL of simulated gastric fluid (pH 1.2, containing pepsin). The same procedure was performed on sample group B.

[0079] Start the dissolution tester, set the temperature to (37.0 ± 0.5)℃ and the rotation speed to 100 r / min; At 30 min, 60 min and 120 min respectively, 5 mL samples were automatically taken from each dissolution vessel and immediately replenished with an equal volume of fresh simulated gastric fluid; The extracted sample was filtered through a 0.45 μm filter membrane and is ready for testing.

[0080] Dissolution test - simulated intestinal stage: After sampling for 120 min, phosphate buffer was added to each dissolution vessel to precisely adjust the pH of the dissolution medium to 6.8, and an appropriate amount of trypsin was added to switch to a simulated intestinal fluid environment; Continue the experiment by taking 5 mL samples at 150 min, 180 min, 240 min, and 360 min, respectively, following the same procedure as above.

[0081] Sample content determination and calculation: The filtrates collected at all time points were injected into a high-performance liquid chromatograph for analysis. Based on the standard curve, the concentrations of palmitoleic acid and linoleic acid in the sample solution at each time point were calculated. The cumulative release rate (%) of the two components at different time points was calculated using the formula.

[0082] The experimental results are shown in Table 2:

[0083] Table 2 Comparison of cumulative release rates of characteristic components in in vitro simulated dissolution tests As shown in Table 2, the in vitro dissolution test data reveal that the dual-effect capsule-in-capsule provided by this invention exhibits significant, two-stage programmed release characteristics in a simulated human digestive tract environment. During the first 120 minutes of the simulated gastric juice stage, the cumulative release rate of palmitoleic acid, representing sea buckthorn fruit oil, reached as high as 94.6%, while the release rate of linoleic acid, representing sea buckthorn seed oil, was only 4.5%, almost negligible. Only after the environment switched to simulated intestinal juice did the release rate of linoleic acid rapidly increase, ultimately resulting in complete release. This result contrasts sharply with traditional capsules that directly mix the two oils, which release both oils simultaneously during the simulated gastric juice stage.

[0084] The unique release behavior described above stems from the specific spatial structure designed in this invention, where the seed oil is inside and the fruit oil is outside. The outer shell disintegrates as expected in a simulated gastric acid environment, releasing the sea buckthorn fruit oil. Meanwhile, the inner capsule, protected by the outer shell, maintains its shell structure, effectively preventing leakage of the sea buckthorn seed oil. Only when the inner capsule enters the neutral environment simulating intestinal fluid does its shell begin to dissolve, thus achieving targeted release of the sea buckthorn seed oil within.

[0085] Therefore, the test results confirm from a functional perspective that this invention is not a simple combination of two oils, but rather, through ingenious structural design, achieves the sequential and regional separation and release of the two functional components in an in vitro digestive environment. This programmed release mode is the technical foundation for transforming the effects of the two oils from simple superposition to true synergistic enhancement, and is the key to distinguishing this invention from existing technologies and enhancing the functional application value of the product.

[0086] Test Example 3: Experimental Objective This test aims to verify the superiority of the low-temperature mild drying process used in Example 1 of this invention in protecting the natural bioactive components of sea buckthorn oil compared with the conventional high-temperature rapid drying process of Comparative Example 5 by quantitatively analyzing the content of key heat-sensitive active ingredients in the capsule contents.

[0087] Experimental samples Sample group A: Dual-effect capsules prepared according to the method of Example 1 of this invention (dried at a low temperature of 25°C).

[0088] Sample group B: Dual-effect capsules prepared according to the method of Comparative Example 5 (dried at 60℃).

[0089] Experimental instruments and reagents Instruments: High-performance liquid chromatograph (HPLC, equipped with diode array detector DAD), analytical balance, ultrasonic cleaner, centrifuge, rotary evaporator.

[0090] Reagents: β-carotene standard, α-tocopherol standard; chromatographic grade n-hexane, isopropanol, methanol.

[0091] Experimental steps Sample pretreatment: 30 capsules were randomly selected from sample group A and sample group B respectively; Cut open each capsule one by one, carefully squeeze all the contents into a precisely weighed 50 mL beaker, weigh it again, and accurately calculate the net weight of the contents. Add 20 mL of n-hexane to a beaker, sonicate for 10 minutes to fully dissolve the fat, and then transfer to a separatory funnel. Extract with a methanol-water solution, separate and collect the n-hexane phase containing the fat-soluble components; The collected n-hexane phase was concentrated to dryness using a rotary evaporator at a low temperature (<40℃); The dried extract was redissolved in chromatographic grade methanol and precisely diluted to 10 mL in a volumetric flask. Before use, the solution was filtered through a 0.22 μm organic phase filter membrane to obtain the sample solution to be tested.

[0092] Preparation of standard curve: Accurately weigh appropriate amounts of β-carotene and α-tocopherol standards, and prepare a series of standard working solutions of different concentrations with methanol.

[0093] HPLC chromatographic analysis: Chromatographic conditions: C18 reversed-phase column (4.6 mm × 250 mm, 5 μm); mobile phase: methanol:acetonitrile:water (gradient elution); flow rate: 1.0 mL / min; column temperature: 30℃.

[0094] Detection conditions: A diode array detector was used to detect β-carotene (representing carotenoids) at a wavelength of 450 nm and α-tocopherol (representing vitamin E) at a wavelength of 292 nm.

[0095] The standard working solution and the sample solution to be tested were injected sequentially for analysis, and the chromatographic peak areas were recorded.

[0096] Content calculation: The concentrations of β-carotene and α-tocopherol in the sample solution are calculated from the peak area based on the standard curve.

[0097] By combining the dilution factor and initial sample weight during the sample pretreatment process, the content of carotenoids (calculated as β-carotene) and vitamin E (calculated as α-tocopherol) in each kilogram of sample oil was finally calculated (mg / kg).

[0098] The experimental results are shown in Table 3: Table 3 Comparison of the effects of different drying processes on the content of key active ingredients Carotenoid content (mg / kg) and Vitamin E content (mg / kg) in each sample group Example 1 (low-temperature drying at 25℃) 286.4 135.8 Comparative Example 5 (dried at 60℃): 161.7 97.3

[0099] The test data in Table 3 clearly reveal the decisive impact of different drying processes on product quality. In Example 1, which uses the low-temperature, gentle drying process of this invention, the contents of carotenoids and vitamin E are significantly higher than those in Comparative Example 5, which uses conventional high-temperature, rapid drying. This result objectively demonstrates the unparalleled superiority of the drying method of this invention in protecting heat-sensitive nutrients.

[0100] The fundamental mechanism behind this difference lies in the fact that the carotenoids and vitamin E abundant in sea buckthorn oil are typical heat-sensitive compounds, whose chemical structures are easily degraded and destroyed under high-temperature conditions. A high-temperature environment of 60°C provides sufficient activation energy for the oxidation and decomposition reactions of these components, leading to the rapid destruction of their molecular structure and thus loss of biological activity. Conversely, the 25°C low-temperature drying process employed in this invention is extremely mild and far from inducing large-scale chemical degradation, thereby allowing these precious natural active ingredients to be preserved to the maximum extent in the final product.

[0101] Therefore, the test results strongly confirm, from an experimental perspective, one of the core innovations of this invention in its preparation method: ensuring high bioactivity of the product through gentle control of the entire process chain, especially the drying stage of the finished product. This precise selection of process parameters is a key technical guarantee for achieving high product quality and ensuring that its functional efficacy is fully realized. It directly reflects the advanced and scientific nature of the preparation method of this invention in maximizing the preservation of the natural value of raw materials.

[0102] Test Example 4: Experimental Objective This test aims to demonstrate, through accelerated aging experiments, that the mass ratio range of sea buckthorn seed oil to fruit oil (1:9 to 3:7) defined in this invention is the optimized range to ensure the product achieves the best chemical stability.

[0103] Experimental samples Sample group A: prepared according to the method of Example 1 of the present invention, with a seed oil to fruit oil mass ratio of 1:3 (within the preferred range).

[0104] Sample group B: Prepared according to the method of Comparative Example 2, with a seed oil to fruit oil mass ratio of 1:19 (below the lower limit of the preferred range).

[0105] Sample group C: prepared according to the method of comparative example 3, with a seed oil to fruit oil mass ratio of 1:1 (higher than the upper limit of the preferred range).

[0106] Experimental instruments and conditions Instruments: constant temperature and humidity incubator, analytical balance, acid burette, iodine flask, and standard laboratory glassware.

[0107] Accelerated aging conditions: temperature set at (40 ± 2)℃, relative humidity set at (75 ± 5)%.

[0108] Experimental steps Initial state confirmation: Before the start of the experiment (month 0), a small number of samples were randomly selected from sample groups A, B and C respectively, and the initial peroxide value and acid value of their contents were determined according to the national standard method to ensure that the initial quality of the three groups of samples was basically consistent.

[0109] Accelerated aging treatment: Place a sufficient quantity of sealed sample groups A, B, and C in the same pre-set temperature and humidity incubator, side by side, to ensure they are subjected to the same aging conditions, and start timing.

[0110] Final sampling and testing: After being stored in the incubator for 6 months, the three groups of samples were taken out simultaneously. A sufficient number of capsules (approximately 20 capsules) were randomly selected from each sample group. Cut open each capsule one by one, carefully squeeze out all the contents into a clean, dry beaker, and mix well.

[0111] According to the methods in GB 5009.227-2016 National Food Safety Standard - Determination of Peroxide Value in Food and GB 5009.229-2016 National Food Safety Standard - Determination of Acid Value in Food, the final peroxide value and acid value of the contents of three groups of samples after aging were determined and the data were recorded.

[0112] The experimental results are shown in Table 4: Table 4. Effects of different oil phase ratios on peroxide value and acid value after 6-month accelerated stability testing.

[0113] The accelerated stability test results in Table 4 clearly show that different formulation ratios have a decisive impact on the stability of the final product. After enduring high temperature and high humidity conditions for up to 6 months, Example 1, using the 1:3 mass ratio of the present invention, maintained extremely low levels of peroxide value and acid value. In stark contrast, Comparative Examples 2 and 3, with ratios below this range (1:19) and above this range (1:1), showed significant increases in peroxide value and acid value. This proves that the formulation ratio range selected in the present invention is not an arbitrary combination, but an optimized scientific range that ensures optimal product stability.

[0114] The underlying mechanism of this phenomenon lies in the fact that the stability of this invention does not solely rely on physical isolation, but also stems from the synergistic protective effect formed between the two oils. Sea buckthorn fruit oil itself is rich in natural antioxidants such as vitamin E and carotenoids, which can provide basic antioxidant protection for the entire system. When the ratio of seed oil to fruit oil is within an optimal range, the quality of antioxidants in the fruit oil and the amount of seed oil that needs protection reach a delicate balance, which can most effectively inhibit the oxidation chain reaction. When the proportion of seed oil is too high, the total amount of easily oxidized substrates in the system increases sharply, exceeding the antioxidant protection capacity provided by the fruit oil, thus leading to a sharp decline in stability.

[0115] Therefore, from the perspective of formulation science, the test results support the present invention's achievement of optimized product stability through precise control of the mass ratio of the two functional oils. This precise control of component proportions is key to ensuring that the technical solution of the present invention can provide a high-quality product with both high efficacy and high stability, demonstrating the advanced nature and originality of the invention's formulation design.

[0116] Test Example 5: Experimental Objective This test aims to verify, through in vitro simulated dissolution experiments, the necessity of the synergistic presence of the two core components, sea buckthorn seed oil and sea buckthorn fruit oil, in this invention. By comparing Example 1 with Comparative Example 4, which lacks sea buckthorn seed oil, it is demonstrated that the expected two-stage programmed release function can only be achieved when the two oils are combined according to the specific structural combination of this invention.

[0117] Experimental samples Sample Group A: Dual-effect capsules (containing seed oil inside and fruit oil outside) prepared according to the method of Example 1 of this invention.

[0118] Sample Group B: Dual-effect capsules prepared according to the method of Comparative Example 4 (both inner and outer capsule contents are sea buckthorn fruit oil).

[0119] Experimental instruments and reagents Instruments: Intelligent dissolution tester (with automatic sampling system), high performance liquid chromatograph (HPLC), analytical balance, pH meter.

[0120] Reagents: hydrochloric acid, pepsin (for preparing simulated gastric juice); phosphate buffer, trypsin (for preparing simulated intestinal juice); palmitoleic acid standard, linoleic acid standard; chromatographic grade methanol, acetonitrile.

[0121] Experimental steps Chromatographic conditions were established: a high-performance liquid chromatography (HPLC) method was developed to accurately and sensitively detect palmitoleic acid (a characteristic component of sea buckthorn fruit oil) and linoleic acid (a characteristic component of sea buckthorn seed oil) in samples.

[0122] Dissolution test - simulated stomach stage: Six tablets of sample group A were placed into six dissolution vessels containing 900 mL of simulated gastric fluid (pH 1.2). The same procedure was performed on sample group B. Start the dissolution tester, set the temperature to (37.0 ± 0.5)℃, the rotation speed to 100 r / min, and continue for 120 minutes; At 60 minutes and 120 minutes, 5 mL samples were automatically taken from each dissolution vessel and replenished with an equal volume of fresh simulated gastric fluid.

[0123] Dissolution test - simulated intestinal stage: After the 120-minute gastric fluid stage, a preset amount of phosphate buffer was added to each dissolution vessel to adjust the pH of the dissolution medium to 6.8, thus switching to a simulated intestinal fluid environment. Continue the experiment, taking 5 mL samples at 180 minutes and 360 minutes respectively, following the same procedure as above.

[0124] Sample analysis and calculation: After appropriate processing, the sample solutions collected at all time points were injected into a high-performance liquid chromatograph to simultaneously detect the concentrations of palmitoleic acid and linoleic acid.

[0125] Based on the measured concentrations, the cumulative release rate (%) of the two characteristic components at different time points was calculated. Components that were not detected were recorded as "not detected".

[0126] The experimental results are shown in Table 5: Table 5. Comparison of the synergistic effect of the two oils in the in vitro dissolution test.

[0127] The dissolution test data in Table 5, through the absence of key components, powerfully demonstrates the completeness and necessity of the technical solution of this invention from the opposite perspective. Example 1 clearly demonstrates the expected two-stage release pattern: in simulated gastric juice, only palmitoleic acid, representing the fruit oil, is released; after entering simulated intestinal juice, linoleic acid, representing the seed oil, begins to be released in large quantities. In decisive contrast, in Comparative Example 4, because both its inner and outer capsules are filled with sea buckthorn fruit oil, no linoleic acid release was detected throughout the entire test. This result irrefutably proves that without sea buckthorn seed oil as the core component, the programmed synergistic release function designed in this invention cannot be realized.

[0128] The fundamental mechanism of this phenomenon lies in the fact that the technical effect of this invention is the inevitable result of the synergistic effect of a specific structure and specific contents. While the physical structure of the capsule-within-a-capsule provides a carrier and possibility for programmed release, the actual component responsible for subsequent intestinal release is the sea buckthorn seed oil encapsulated within the inner capsule. In Example 1, after the outer capsule releases the fruit oil, the intact inner capsule transports the seed oil to the simulated intestinal environment, thereby releasing linoleic acid, thus fully realizing the release sequence of fruit oil first, followed by seed oil. In Comparative Example 4, although the inner and outer capsule structures are also present, the absence of the sea buckthorn seed oil in the inner capsule prevents the release of its characteristic component, linoleic acid, in the second stage, resulting in an interruption of its functional chain.

[0129] Therefore, the test results demonstrate from the perspective of component synergy that the superiority of this invention does not solely stem from a novel physical structure, but rather from the organic combination of this structure with two specific functional components: sea buckthorn seed oil and sea buckthorn fruit oil. Both oil components are indispensable for achieving the final technical effect of this invention, together constituting a complete technical solution for achieving a synergistic dual-effect. This fully illustrates the originality and necessity of the composition of this invention; that is, the two specific oils must be combined in the manner of this invention to achieve the expected functional goals.

[0130] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A dual-effect capsule containing sea buckthorn seed oil and fruit oil, characterized in that, include: The inner capsule contains sea buckthorn seed oil and the outer capsule contains sea buckthorn fruit oil, wherein the mass ratio of sea buckthorn seed oil to sea buckthorn fruit oil is 1:9 to 3:

7. The sea buckthorn seed oil contains 50%–70% linoleic acid, 10%–30% linolenic acid, and 5%–15% oleic acid. The sea buckthorn fruit oil contains 20%–40% palmitoleic acid, 20%–40% oleic acid, and 0.005%–0.03% carotenoids. The inner capsule shell is composed of gelatin, glycerin, and purified water; The outer capsule shell is composed of gelatin, glycerin, purified water and food coloring.

2. The dual-effect capsule of sea buckthorn seed oil and fruit oil according to claim 1, characterized in that, The inner capsule contains 100–300 mg of sea buckthorn seed oil, and the outer capsule contains 200–500 mg of sea buckthorn fruit oil.

3. The dual-effect capsule of sea buckthorn seed oil and fruit oil according to claim 1, characterized in that, Both the inner capsule and the outer capsule are soft capsule structures, with the inner capsule completely embedded inside the outer capsule, forming a capsule-within-a-capsule structure.

4. The dual-effect capsule of sea buckthorn seed oil and fruit oil according to claim 1, characterized in that, The capsule contains natural antioxidants, selected from vitamin E, tea polyphenols, or rosemary extract, to improve stability.

5. The dual-effect capsule of sea buckthorn seed oil and fruit oil according to claim 1, characterized in that, The sea buckthorn seed oil and sea buckthorn fruit oil were obtained by supercritical CO2 extraction.

6. A method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil according to any one of claims 1-5, characterized in that, Includes the following steps: S1. Extract sea buckthorn seed oil and sea buckthorn fruit oil separately; S2. Seabuckthorn seed oil is filled into the inner capsule shell material to prepare the inner capsule; S3. Place the inner capsule in the outer capsule forming mold and inject a mixture of sea buckthorn fruit oil and outer capsule shell material to form an outer capsule, thus obtaining a capsule-within-a-capsule structure. S4. Dry and shape to obtain capsules within capsules.

7. The method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil according to claim 6, characterized in that, In step S1, sea buckthorn seed oil and sea buckthorn fruit oil are extracted using supercritical CO2 fluid extraction at a temperature of 35–50°C and a pressure of 25–35 MPa.

8. The method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil according to claim 6, characterized in that, The inner bladder is formed using the droplet method or the drum droplet method, while the outer bladder is formed using the rotary molding method or the plunger filling method.

9. The method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil according to claim 6, characterized in that, In step S4, the drying process adopts constant temperature forced air drying, with a temperature of 20-30℃ and a time of 24-48 hours.

10. The method for preparing a dual-effect capsule of sea buckthorn seed oil and fruit oil according to claim 6, characterized in that, Adding vitamin E or rosemary extract to the capsule material can improve the antioxidant stability and shelf life of the product.

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