A complex vegetable oil composition for regulating blood lipid and preparation thereof

Abstract

The application discloses a kind of compound vegetable oil composition and preparation for adjusting blood fat.The composition is composed of oil phase component and active component: the oil phase component includes flaxseed oil, perilla seed oil, safflower seed oil, olive oil and sesame oil;Active component includes phytosterol ester, sesame lignan and natural vitamin E;The mass ratio of sesame lignan and phytosterol ester is 1:5-1:30, and the mass ratio of omega-6 and omega-3 polyunsaturated fatty acid in the composition is 1:1-4:1.A self-microemulsifying preparation comprising the composition, medium-chain triglyceride and hydrophilic surfactant is also provided.The application significantly reduces the levels of serum total cholesterol, triglycerides and low-density lipoprotein cholesterol, increases the level of high-density lipoprotein cholesterol by synergistic effect of phytosterol ester and sesame lignan and precise ratio of omega-6 / omega-3, and has excellent oxidative stability and high bioavailability of active ingredients.

Description

Technical Field

[0001] This invention relates to the field of edible oil and functional food technology, and in particular to a compound vegetable oil composition for regulating blood lipids and its preparation, as well as a self-microemulsifying preparation containing the composition, a method for preparing the composition, and the application of the composition and preparation in the preparation of health foods, special medical purpose formula foods or functional edible oils that assist in regulating blood lipids. Background Technology

[0002] Dyslipidemia, commonly known as hyperlipidemia, is a group of lipid metabolism disorders characterized by elevated levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and / or decreased levels of high-density lipoprotein cholesterol (HDL-C) in blood plasma. Dyslipidemia is one of the most important independent risk factors for cardiovascular and cerebrovascular diseases such as atherosclerosis, coronary heart disease, myocardial infarction, and stroke.

[0003] Currently, commonly used lipid-lowering drugs in clinical practice mainly include statins, fibrates, niacin, and cholesterol absorption inhibitors. However, drug treatment has certain limitations: long-term use of statins may lead to adverse reactions such as elevated transaminase levels, myopathy, and rhabdomyolysis, and some patients experience intolerance or poor adherence; fibrates and niacin also have their own applicable ranges and adverse reaction profiles. Therefore, lipid management through dietary means, especially through the use of functional edible oils or health supplements to assist in lipid regulation, has received widespread attention from the medical community and consumers due to its high safety and long-term adherence.

[0004] Vegetable oils are rich in unsaturated fatty acids and various natural active ingredients, making them an ideal substrate for developing functional foods that help regulate blood lipids. Regarding the topic of "lipid-lowering vegetable oil compositions," numerous patent applications have been published both domestically and internationally. After reviewing existing technologies, the inventors have identified the following main technical approaches and their shortcomings:

[0005] The first type of technical route is the "simple compounding of multiple oils" route, which involves directly mixing multiple plant oils in a certain proportion, relying on the endogenous components of the oils to achieve lipid-lowering effects. For example, Chinese patent application CN103385315A discloses a plant oil composition with lipid-lowering effects and its preparation method, which is made from 5-50 parts of jujube seed oil, 10-80 parts of Artemisia argyi seed oil, 5-50 parts of perilla seed oil, 10-80 parts of flaxseed oil, and 5-50 parts of grape seed oil. It achieves the effect of regulating blood lipids through the compounding of multiple medicinal and edible plant oils. This scheme relies entirely on the endogenous components of the plant oils themselves, without involving the addition and synergistic design of exogenous functional active ingredients. Its lipid-lowering strength is limited, and no formulation is disclosed. The bioavailability of fat-soluble active ingredients is difficult to guarantee, and oxidative stability is not specifically designed.

[0006] The second type of technical route is the "direct ratio of fatty acid monomers or active ingredients" route. For example, Chinese patent application CN103284151A discloses an ω-3 unsaturated plant oil with lipid-lowering effects, which is composed of oleic acid, linoleic acid, α-linolenic acid, vitamin E, sesamin, sesamol, proanthocyanidins, and perillaldehyde in specific weight parts, or formulated from sunflower seed oil, grape seed oil, black sesame oil, perilla oil, perilla volatile oil, and sesame lignans in a certain proportion. Although this scheme introduces sesame lignans and emphasizes its antioxidant and lipid-lowering effects, it does not involve the addition of phytosterol esters, does not disclose the synergistic compatibility between phytosterol esters and sesame lignans, and does not systematically limit the mass ratio of ω-6 and ω-3 polyunsaturated fatty acids in the composition. Therefore, it is difficult to achieve multi-target synergistic effects in the key lipid-lowering link of "inhibiting cholesterol intestinal absorption". Its lipid-lowering effect mainly relies on the conventional physiological effects of unsaturated fatty acids, and its strength is limited.

[0007] The third type of technical route is the "plant oil compounded with phytosterols (esters)" route. For example, Chinese patent application CN113973929A discloses a lipid-lowering health care combination oil and its preparation method, which is composed of 30-40% corn germ oil, 35-45% flaxseed oil, 1-5% sesame oil, 1-2% phytosterols, and the balance soybean oil by mass percentage. It utilizes the effect of phytosterols to inhibit cholesterol absorption in the intestine to achieve lipid-lowering. However, this scheme only uses phytosterols as the core single active ingredient, without introducing active ingredients such as sesame lignans that have the function of inhibiting endogenous cholesterol synthesis and promoting cholesterol excretion, and lacks a multi-target synergistic regulatory mechanism; it mainly uses bulk oils such as corn germ oil and soybean oil, with limited α-linolenic acid content, and does not regulate the ratio of ω-6 to ω-3 polyunsaturated fatty acids; moreover, it adopts a simple stirring preparation process at 45-55℃, and the dispersion uniformity, oxidative stability, and batch consistency of active ingredients are not ideal. This application was also rejected because it does not have outstanding substantive features.

[0008] The fourth type of technical route is the "multi-oil compounding and refining" route. For example, Chinese patent application CN115281250A discloses a lipid-lowering edible oil formula and its preparation process, which is made from 62-125 parts of base oil (composed of 10-25 parts of flaxseed oil, 2-20 parts of safflower seed oil and 50-80 parts of sunflower seed oil), 0.2-0.6 parts of vitamin E, 2-15 parts of walnut oil, 2-10 parts of tea seed oil, 5-25 parts of perilla oil, 2-10 parts of olive oil and 2-10 parts of sesame oil, and is processed through refining processes such as phosphoric acid degumming, bleaching clay decolorization and steam deodorization. Although the scheme involves the blending of various vegetable oils and takes into account the increase of linoleic acid and linolenic acid content, it also does not involve the synergistic combination of phytosterol esters and sesame lignans, does not precisely limit the mass ratio of ω-6 and ω-3 polyunsaturated fatty acids, and the high-temperature refining process (decolorization and deodorization) will significantly lose the natural vitamin E, phytosterols and other active ingredients in the oil. It does not disclose any formulation technology to improve the bioavailability of active ingredients.

[0009] The fifth type of technical route is the "regulation of endogenous trace components". For example, Chinese patent application CN112042767A discloses an edible vegetable blended oil that lowers blood lipids and cholesterol. It achieves its lipid-lowering effect by controlling the content range of endogenous trace components such as polyphenols, β-sitosterol, campesterol, stigmasterol, squalene, paclitaxel, and γ-tocotrienol in the finished oil. In this scheme, all trace components are derived from the endogenous components of the selected oil variety, representing the screening and regulation of existing endogenous component content. It does not involve the technical concept of adding exogenous phytosterol esters and sesame lignans and controlling their mass ratio. Because the content of endogenous trace components fluctuates greatly due to factors such as raw material origin, variety, and processing technology, this scheme suffers from poor batch stability, making it difficult to guarantee the repeatability of the lipid-lowering effect and hindering the precise control of active ingredients during industrial-scale production.

[0010] In addition, some existing technologies involve self-microemulsification or microencapsulation of plant oils, such as preparing self-emulsifying soft capsules from ω-3 sources like fish oil and algal oil to improve their absorption. However, most of these preparations use fish oil or algal oil as the active source and do not involve self-microemulsification delivery systems based on terrestrial plant oil compositions such as flaxseed oil and perilla seed oil. Furthermore, they do not disclose the synergistic combination of phytosterol esters and sesame lignans to prepare self-microemulsifying preparations to simultaneously improve the bioavailability of both.

[0011] In summary, the lipid-lowering plant oil compositions disclosed in the prior art have the following common shortcomings: (1) Most of them use a single active ingredient or rely solely on the endogenous components of the oil, lacking a synergistic design between active ingredients based on different lipid-lowering targets, resulting in limited lipid-lowering effects; (2) Generally, the mass ratio of ω-6 and ω-3 polyunsaturated fatty acids in the composition is not systematically regulated, and this ratio directly affects the conversion efficiency of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the body and the balance of inflammation regulation, thereby affecting the lipid regulation effect; (3) There is a lack of formulation design targeting the bioavailability of fat-soluble active ingredients (especially phytosterol esters), resulting in low absorption rate of active ingredients in the intestine; (4) Most compositions are not equipped with a synergistic antioxidant system, and plant oils rich in polyunsaturated fatty acids are prone to oxidation and rancidity during storage, making it difficult to guarantee shelf-life quality; (5) Some schemes use high-temperature refining or simple stirring processes, resulting in large loss of active ingredients, uneven dispersion, and poor batch stability.

[0012] Therefore, there is an urgent need in the field for a compound vegetable oil composition and its formulation that can simultaneously achieve "multi-target synergistic lipid reduction, precise ω-6 / ω-3 fatty acid ratio, high bioavailability of active ingredients, excellent oxidative stability, and good batch-to-batch consistency" to meet the needs of long-term dietary intervention for people with dyslipidemia. This invention is proposed based on the aforementioned technical requirements. Summary of the Invention

[0013] To address the shortcomings of existing technologies, the present invention aims to provide a compound plant oil composition and its formulation for regulating blood lipids. One objective of the present invention is to provide a compound plant oil composition for regulating blood lipids, which achieves multi-target, high-efficiency, and long-term safe blood lipid regulation effects through the synergistic effect of phytosterol esters and sesame lignans, the precise ratio of ω-6 and ω-3 polyunsaturated fatty acids, and the antioxidant synergistic system composed of natural vitamin E and sesame lignans.

[0014] The second objective of this invention is to provide a method for preparing the above-mentioned compound vegetable oil composition. Through the synergistic cooperation of processes such as low-temperature pressing, pre-dispersion of active components, nitrogen-filled mixing, high-pressure homogenization, and cooling degassing, the active components are ensured to be uniformly and stably dispersed in the oil phase, maximizing the retention of the biological activity of polyunsaturated fatty acids and active ingredients, and improving the oxidative stability and batch consistency of the composition.

[0015] The third objective of this invention is to provide a self-microemulsifying formulation comprising the above-mentioned composite plant oil composition. By constructing a self-microemulsifying delivery system using medium-chain triglycerides and hydrophilic surfactants, the fat-soluble active ingredients (especially phytosterol esters) spontaneously form nanoscale microemulsions upon contact with gastrointestinal fluid, significantly improving the dissolution and bioavailability of the active ingredients.

[0016] The above-mentioned objective of this invention is achieved through the following technical solutions:

[0017] A compound plant oil composition for regulating blood lipids, the composition comprising an oil phase component and an active component; the oil phase component includes flaxseed oil, perilla seed oil, safflower seed oil, olive oil, and sesame oil; the active component includes phytosterol esters, sesame lignans, and natural vitamin E; the mass ratio of sesame lignans to phytosterol esters is 1:5 to 1:30; based on the mass of total fatty acids in the composition, the mass ratio of ω-6 polyunsaturated fatty acids to ω-3 polyunsaturated fatty acids in the composition is 1:1 to 4:1.

[0018] Further, based on a total mass of 100 parts of the composition, the content of each component is as follows: 25-45 parts flaxseed oil, 5-20 parts perilla seed oil, 10-30 parts safflower seed oil, 10-25 parts olive oil, 2-8 parts sesame oil, 1.5-5 parts phytosterol esters, 0.05-0.5 parts sesame lignans, and 0.02-0.2 parts natural vitamin E. Within the above range, flaxseed oil and perilla seed oil together provide abundant α-linolenic acid (ω-3 series), safflower seed oil provides high-purity linoleic acid (ω-6 series), olive oil provides monounsaturated fatty acids and improves oxidative stability and flavor, and sesame oil provides natural lignan precursors and characteristic flavor. After blending, the mass ratio of ω-6 series to ω-3 series polyunsaturated fatty acids can be controlled within the range of 1:1 to 4:1, while ensuring a reasonable composition of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. It should be noted that when the composition is formulated within the part range defined in claim 2, the mass ratio of ω-6 to ω-3 polyunsaturated fatty acids in the resulting composition usually falls within the range of 1:1 to 2:1. If it is necessary to further increase this ratio (e.g., 2:1 to 4:1) within the range of 1:1 to 4:1 defined in claim 1, this can be achieved by moderately adjusting the relative proportions between the oil phase components (e.g., partially replacing flaxseed oil and perilla seed oil with safflower seed oil) while keeping the types of oil phase components and active components unchanged. Example 9 provides a specific example and effect data of this adjustment method. In addition, the sesame lignans described in this invention are exogenously added active components, extracted and refined from by-products such as sesame oil residue, and are different from the trace amounts of endogenous lignans naturally present in sesame oil. Those skilled in the art can clearly distinguish between the two based on the description in this invention and can avoid confusing them.

[0019] Furthermore, the content of γ-tocotrienol in the composition is not less than 30 mg / 100g. γ-Tocotrienol is mainly derived from the selected palm oil-derived natural vitamin E and sesame oil. It has a stronger free radical scavenging ability and higher cell membrane affinity than α-tocopherol, and together with sesame lignans, it forms a highly efficient antioxidant network.

[0020] Furthermore, based on the mass of the total fatty acids in the composition, the content of saturated fatty acids in the composition is no more than 12%, the content of monounsaturated fatty acids is 25%–45%, and the content of polyunsaturated fatty acids is 40%–65%, and the mass ratio of ω-6 polyunsaturated fatty acids to ω-3 polyunsaturated fatty acids is 1.5:1–3:1. This fatty acid composition balances lipid-lowering effects, oxidative stability, and taste quality.

[0021] Furthermore, the phytosterol ester contains at least 50% β-sitosterol ester by mass, with the remainder being at least one of campesterol ester and stigmasterol ester; the esterification rate of the phytosterol ester is at least 95%. Phytosterol esters with high esterification rates have good lipid solubility, making them easy to dissolve and disperse uniformly in the oil phase, and after being hydrolyzed by pancreatic cholesterol esterase in the intestine, they release free phytosterols to exert an inhibitory effect on cholesterol absorption.

[0022] Furthermore, the sesame lignans comprises sesamin and sesamol, wherein the mass ratio of sesamin to sesamol is 3:1 to 10:1. Sesamin is metabolized in vivo by intestinal flora into active metabolites such as sesamol, and sesamol has stronger free radical scavenging activity; the combination of the two in the above ratio can exert a synergistic effect in inhibiting cholesterol synthesis and antioxidation.

[0023] The present invention also provides a method for preparing the above-mentioned compound vegetable oil composition, comprising the following steps:

[0024] S1. Raw material pretreatment: Flaxseed, perilla seed, safflower seed, olive fruit and sesame were pressed at low temperature to obtain flaxseed oil, perilla seed oil, safflower seed oil, olive oil and sesame oil. The peroxide value of each oil was not higher than 3 mmol / kg.

[0025] S2. Weighing and mixing: Weigh each oil phase component and active component according to the composition ratio of the composition;

[0026] S3. Pre-dispersion of active components: Plant sterol esters, sesame lignans and natural vitamin E are added to a mixture of sesame oil and olive oil and stirred at 65-75°C to dissolve them, thus obtaining an oil solution of active components.

[0027] S4. Nitrogen-purified mixing: The active component oil solution is mixed with flaxseed oil, perilla seed oil and safflower seed oil under nitrogen protection conditions, and stirred at 25-35℃ and 60-120r / min for 30-60min to obtain the mixed oil.

[0028] S5. High-pressure homogenization: The mixed oil is homogenized 1 to 3 times under a pressure of 20 to 40 MPa to obtain homogenized oil;

[0029] S6. Cooling and degassing: Cool the homogenized oil to below 20°C and perform vacuum degassing;

[0030] S7. Quality Inspection: The fatty acid composition, phytosterol ester content, sesame lignan content, peroxide value, and mass ratio of ω-6 to ω-3 polyunsaturated fatty acids in the homogenized oil are tested. If the results are qualified, the composite vegetable oil composition is obtained.

[0031] S8. Filling: Fill and seal the qualified compound vegetable oil composition.

[0032] This invention also provides a self-microemulsifying compound plant oil formulation for regulating blood lipids. The formulation comprises the aforementioned compound plant oil composition, medium-chain triglycerides, and a hydrophilic surfactant. The mass ratio of the compound plant oil composition, medium-chain triglycerides, and hydrophilic surfactant is 55–75:10–25:15–30. The formulation spontaneously emulsifies upon contact with water or gastrointestinal fluid to form a microemulsion with an average particle size not exceeding 200 nm. The medium-chain triglycerides (MCT, C8–C10 carbon chain) act as a solubilizer for lipid-soluble active ingredients such as phytosterol esters, increasing their solubility in the oil phase and improving self-microemulsification efficiency. The hydrophilic surfactant (HLB value 10–15) endows the system with the ability to spontaneously form nanoemulsions under gastrointestinal peristalsis, increasing the oil-water interface area, promoting the hydrolytic emulsification of phytosterol esters by lipases and bile salts, and enhancing absorption rate via the lymphatic pathway.

[0033] Furthermore, the hydrophilic surfactant is selected from at least one of polysorbate 80, polyglycerol ricinoleate, and sucrose fatty acid ester; the formulation is a soft capsule or a microcapsule powder.

[0034] The present invention also provides the application of the above-mentioned compound vegetable oil composition or the above-mentioned compound vegetable oil self-microemulsifying preparation in the preparation of health foods, special medical purpose formula foods or functional edible oils that help regulate blood lipids.

[0035] In summary, compared with the prior art, the present invention has at least one of the following beneficial technical effects:

[0036] Multi-target synergistic lipid-lowering: This invention synergistically combines phytosterol esters and sesame lignans at a mass ratio of 1:5 to 1:30. After hydrolyzing into free phytosterols in the intestine, the phytosterol esters compete with cholesterol for absorption sites on the intestinal microvilli membrane, inhibiting cholesterol absorption (first target for lipid-lowering). Sesame lignans (mainly sesamin, sesamol, and their metabolites) can inhibit the activity of hepatic hydroxymethylglutaryl-CoA (HMG-CoA) reductase, reducing endogenous cholesterol synthesis, and upregulate the expression of low-density lipoprotein receptor (LDLR) in hepatocytes, promoting the conversion of cholesterol to bile acids and their excretion in feces (second and third targets for lipid-lowering). Both act on the three key links of cholesterol metabolism—intestinal absorption, hepatic synthesis, and bile excretion—forming a multi-target synergistic regulatory mechanism of "inhibiting absorption + inhibiting synthesis + promoting excretion." Animal studies have shown that, under the premise of the same total amount of added active ingredients, the combination of phytosterol esters and sesame lignans in a mass ratio of 1:5 to 1:30 significantly reduces serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) better than the combination of adding phytosterol esters alone or adding sesame lignans alone, and is better than the simple sum of the effects of the two, proving that there is a significant synergistic effect between the two (see Example 7 for details).

[0037] Precise Ratio of ω-6 / ω-3 Fatty Acids: This invention utilizes a blend of flaxseed oil, perilla seed oil (a source of ω-3 α-linolenic acid), and safflower seed oil (a source of ω-6 linoleic acid) to control the mass ratio of ω-6 to ω-3 polyunsaturated fatty acids in the composition to be 1:1 to 4:1 (preferably 1.5:1 to 3:1). This ratio is lower than the ω-6 / ω-3 ratio in a conventional diet (the ω-6 / ω-3 ratio in the diet of Chinese residents is usually as high as 10:1 to 20:1), which can effectively inhibit the conversion of ω-6 arachidonic acid (AA) into pro-inflammatory prostaglandins and leukotrienes in the body, and reduce vascular inflammatory responses. At the same time, sufficient α-linolenic acid substrate can improve its conversion efficiency to EPA and DHA in the body, thereby reducing triglyceride synthesis and improving vascular endothelial function through the EPA / DHA pathway. Comparative experiments show that, under the premise that the other components and total polyunsaturated fatty acid content of the composition are basically the same, when the ω-6 / ω-3 mass ratio is 1:1 to 4:1, the composition reduces serum triglycerides (TG) by a significantly greater extent than the composition with an ω-6 / ω-3 mass ratio greater than 4:1 (see Example 9 for details).

[0038] Antioxidant Synergistic System: Natural vitamin E (containing α-tocopherol, γ-tocopherol, and γ-tocotrienol) and sesame lignans constitute a "phenolic + lignan" complex antioxidant system. γ-Tocotrienols have stronger free radical scavenging ability and higher membrane affinity than α-tocopherols; sesamin in sesame lignans is metabolized in vivo into active metabolites such as sesamol, which can form a regenerative cycle with vitamin E, delaying the consumption of vitamin E. The synergistic effect of the two can effectively inhibit the oxidation of polyunsaturated fatty acids such as α-linolenic acid and linoleic acid in the composition, extending the oxidation induction period of the composition in the 120℃ accelerated oxidation test (Rancimat method) by more than 45% compared with the control composition that only added an equal amount of vitamin E. After 12 months of storage at 25℃ in the dark, the peroxide value is still no higher than 5 mmol / kg, which is significantly better than ordinary commercially available blended oils, ensuring the quality stability of the product during its shelf life (see Example 6 for details).

[0039] High bioavailability formulation design: This invention utilizes a self-microemulsifying delivery system constructed from medium-chain triglycerides (MCT) and a hydrophilic surfactant. MCT, acting as a "molecular solvent" for the lipid-soluble active ingredient, increases the solubility of phytosterol esters in the oil phase. The hydrophilic surfactant causes the formulation to spontaneously form microemulsion droplets with a particle size no larger than 200 nm upon contact with gastrointestinal fluid, increasing the oil-water interface area, promoting the emulsification and hydrolysis of phytosterol esters by lipases and bile salts, and facilitating absorption via the lymphatic pathway. Rat pharmacokinetic studies showed that the cumulative 24-hour absorption of phytosterol esters from the self-microemulsifying soft capsules of this invention was approximately 2.3 times higher than that of ordinary mixed-oil soft capsules, with a peak plasma concentration (Cmax) approximately 2.1 times higher and an area under the curve (AUC0-24h) approximately 2.0 times higher, significantly improving the bioavailability of the active ingredient (see Example 8 for details).

[0040] Process Synergy Guarantee: This invention employs a preparation process of "low-temperature pressing + pre-dispersion of active components + nitrogen-filled mixing + high-pressure homogenization + cooling and degassing". Low-temperature pressing (pressing temperature not exceeding 55℃) maximizes the preservation of natural active ingredients in the oil. The pre-dispersion step first dissolves phytosterol esters, sesame lignans, and vitamin E in a mixture of sesame oil and olive oil at 65-75℃, avoiding the destruction of polyunsaturated fatty acids by prolonged high-temperature heating, while ensuring uniform dispersion of active components. Nitrogen-filled protection and vacuum degassing isolate oxygen, reducing oxidation losses during processing. High-pressure homogenization enables the active components to achieve submicron-level dispersion in the oil phase, preventing stratification and precipitation. The composition prepared by this process shows no stratification or precipitation after standing at room temperature for 90 days, with an active ingredient content deviation of less than 5%, and excellent batch stability (see Example 5 for details).

[0041] Safety and Adaptability: All components of this invention are edible oils, food additives, or new food ingredients permitted by national standards such as GB2760 "National Food Safety Standard for the Use of Food Additives" and GB2716 "National Food Safety Standard for Vegetable Oils" (plant sterol esters and sesame lignans respectively meet the requirements of the National Health Commission's announcement on plant sterol esters and sesame lignans as new food ingredients). It contains no chemically synthesized drug components, has high safety, and can be consumed long-term. It is suitable for adjunctive dietary intervention in people with hypercholesterolemia, hypertriglyceridemia, and mixed hyperlipidemia, and can also be used as a functional edible oil for preventing dyslipidemia in the general population, with broad market application prospects. Attached Figure Description

[0042] Figure 1 This is a process flow diagram of the preparation method of the composite vegetable oil composition provided in Example 1 of the present invention. Detailed Implementation

[0043] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.

[0044] The present invention will be further described in detail below with reference to specific embodiments. The following embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise stated, the raw materials used in the following embodiments are all commercially available food-grade raw materials, and the specific specifications of each raw material are as follows:

[0045] Flaxseed oil: Made from flaxseeds grown in Inner Mongolia, processed by low-temperature pressing (pressing temperature not exceeding 55℃), with an α-linolenic acid content of not less than 50wt%, a linoleic acid content of not less than 15wt%, and a peroxide value not exceeding 2.0mmol / kg; Perilla seed oil: Made from perilla seeds grown in Jilin, processed by low-temperature pressing, with an α-linolenic acid content of not less than 55wt%, a linoleic acid content of not less than 12wt%, and a peroxide value not exceeding 2.0mmol / kg; Safflower seed oil: Made from flaxseeds grown in Xinjiang. Safflower seeds, processed by low-temperature pressing, contain no less than 75 wt% linoleic acid and no more than 2.0 mmol / kg peroxide value; Olive oil: Extra virgin olive oil, containing no less than 65 wt% oleic acid, no less than 8 wt% linoleic acid, and no more than 2.0 mg KOH / g acid value; Sesame oil: White sesame oil pressed using the water-displacement method, containing no less than 400 mg / 100g sesamin (total sesamin and sesamol) and no less than 42 wt% linoleic acid. Oleic acid content not less than 40 wt%; Phytosterol esters: Phytosterol esters prepared by enzymatic esterification of soybean phytosterols and sunflower seed oil fatty acids, wherein the β-sitosterol ester content is not less than 50 wt%, the total content of rapeseed oil sterol ester and stigmasterol ester is not less than 30 wt%, and the esterification rate is not less than 95%; Sesamolene: Sesamolene extract extracted from sesame oil residue, wherein the total content of sesamin and sesamol is not less than 90 wt%, and the mass ratio of sesamin to sesamol is 3:1. :1~10:1 (In Example 1, an extract with a sesamin to sesamol mass ratio of 6:1 was used); Natural Vitamin E: Natural mixed tocopherols and tocotrienols extracted from deodorized palm oil distillate were selected, with a total tocopherol content of not less than 95wt% and a γ-tocotrienol content of not less than 40wt%; Medium-chain triglycerides (MCT): Food-grade medium-chain triglycerides with carbon chains of C8~C10 were selected; Polysorbate 80, polyglycerol ricinoleate, and sucrose fatty acid esters: All were food-grade.

[0046] The detection methods involved in the examples are as follows: fatty acid composition was determined by gas chromatography (GC, according to GB5009.168-2016); phytosterol esters and sesame lignans were determined by high performance liquid chromatography (HPLC); γ-tocotrienols were determined by HPLC; peroxide value was determined according to GB5009.227-2016; acid value was determined according to GB5009.229-2016; oxidation induction period was determined according to GB / T21121-2007 (Rancimat method); and microemulsion particle size was determined by Malvern laser particle size analyzer.

[0047] Example 1

[0048] This embodiment provides a compound plant oil composition for regulating blood lipids and its preparation method. Based on a total mass of 100 parts, the contents of each component are as follows: 25 parts flaxseed oil, 10 parts perilla seed oil, 30 parts safflower seed oil, 22 parts olive oil, 8 parts sesame oil, 4.5 parts phytosterol esters, 0.3 parts sesame lignans, and 0.2 parts natural vitamin E. The mass ratio of sesame lignans to phytosterol esters was 0.3:4.5 = 1:15. According to GC analysis, based on the mass of total fatty acids (i.e., fatty acid glycerides in the oil phase component, the same below), the mass fraction of ω-6 polyunsaturated fatty acids (calculated as linoleic acid) in the composition was 34.6%, the mass fraction of ω-3 polyunsaturated fatty acids (calculated as α-linolenic acid) was 20.3%, and the mass ratio of the two was 1.7:1. The saturated fatty acid content was 10.3%, the monounsaturated fatty acid content was 30.3%, and the polyunsaturated fatty acid content was 59.4%. According to HPLC detection, the γ-tocotrienol content was 82 mg / 100g.

[0049] The composite vegetable oil composition of this embodiment is in accordance with Figure 1 The preparation process shown is as follows:

[0050] S1. Raw material pretreatment: Flaxseed, perilla seed, safflower seed, olive fruit, and sesame seeds are taken separately, cleaned and impurities removed, and then pressed at a low temperature not exceeding 55℃ to obtain flaxseed oil, perilla seed oil, safflower seed oil, olive oil, and sesame oil, respectively. Each oil is filtered to remove impurities, and the peroxide value of each oil is tested to be no higher than 2.0 mmol / kg, and the acid value is no higher than 2.0 mg KOH / g. After meeting the quality requirements of step S1, the oil is ready for use.

[0051] S2. Weighing and Blending: Weigh out 25 kg of flaxseed oil, 10 kg of perilla seed oil, 30 kg of safflower seed oil, 22 kg of olive oil, 8 kg of sesame oil, 4.5 kg of phytosterol esters, 0.3 kg of sesame lignans, and 0.2 kg of natural vitamin E according to the above proportions, and set aside. Sesame oil and olive oil will be combined as the pre-dispersed solvent oil in step S3, and flaxseed oil, perilla seed oil, and safflower seed oil will be combined as the subsequent added oil phase in step S4.

[0052] S3. Pre-dispersion of active components: Add 4.5 kg of weighed phytosterol esters, 0.3 kg of sesame lignans, and 0.2 kg of natural vitamin E to a mixture of 8 kg of sesame oil and 22 kg of olive oil. Stir at 100 rpm for 30 minutes at 70°C until the mixture is clear and transparent with no visible particles, thus obtaining an oil solution of the active components. This pre-dispersion step utilizes the rich natural antioxidants and good solubility of sesame oil and olive oil to allow phytosterol esters, sesame lignans, and vitamin E to dissolve and disperse quickly and uniformly at a lower temperature. This avoids the risk of localized overheating and oxidation caused by directly adding active components to flaxseed oil, perilla seed oil, or safflower seed oil, which are high in polyunsaturated fatty acids. It also avoids the ester hydrolysis and activity loss that may occur when phytosterol esters are heated for extended periods above 75°C.

[0053] S4. Nitrogen-purified mixing: The active component oil solution obtained in S3, along with 25 kg of weighed flaxseed oil, 10 kg of perilla seed oil, and 30 kg of safflower seed oil, are added to a mixing tank equipped with a nitrogen-purified protection device and a stirrer. High-purity nitrogen gas (purity ≥99.9%) is introduced into the tank to replace the air until the oxygen volume fraction is below 0.5%. Then, the mixture is stirred and mixed at 30℃ and 90 r / min for 45 min to obtain the mixed oil. Nitrogen purging protection is maintained throughout the entire mixing process, effectively isolating oxygen and preventing the oxidation of polyunsaturated fatty acids such as α-linolenic acid and linoleic acid during mixing.

[0054] S5. High-pressure homogenization: The mixed oil obtained in S4 is fed into a high-pressure homogenizer and homogenized twice at a pressure of 30 MPa to obtain homogenized oil. Homogenization enables the active components such as phytosterol esters and sesame lignans to achieve submicron-level dispersion in the oil phase, forming a uniform and stable oil dispersion system. Microscopic observation revealed no active component particles larger than 10 μm in diameter.

[0055] S6. Cooling and degassing: Cool the homogenized oil obtained in S5 to 18°C, transfer it to a vacuum degassing tank, and degas it for 30 minutes under a vacuum of 0.08 MPa to remove dissolved oxygen and trace bubbles from the oil, thus obtaining degassed oil.

[0056] S7. Quality Inspection: Samples of degassed oil were tested: the fatty acid composition was determined by GC method, and the calculated mass ratio of ω-6 series to ω-3 series polyunsaturated fatty acids was 1.7:1, which meets the requirement of 1:1 to 4:1; the phytosterol ester content was determined by HPLC method to be 4.48 parts (equivalent to 4.48g of phytosterol ester per 100g of composition), the sesame lignan content was 0.29 parts (equivalent to 290mg of sesame lignan per 100g of composition), and the γ-tocotrienol content was 82mg / 100g; the peroxide value was determined according to GB5009.227 to be 0.8mmol / kg, which meets the requirement of not exceeding 3mmol / kg; after all indicators are qualified, the compound vegetable oil composition of this embodiment is obtained.

[0057] S8. Filling: Fill the qualified compound vegetable oil composition into sterilized glass bottles or food-grade PET bottles under nitrogen filling conditions, and seal them to obtain the finished compound vegetable oil composition.

[0058] The compound vegetable oil composition prepared in this embodiment is a clear and transparent oily liquid with a complex flavor of sesame and olive. It does not separate or precipitate after standing at room temperature for 90 days. The content deviation of active ingredients is less than 5%, and it has excellent oxidative and dispersion stability.

[0059] Example 2

[0060] This embodiment provides a compound plant oil composition for regulating blood lipids, differing from Example 1 only in the proportions of its components. Based on a total composition mass of 100 parts, the components are: 28.4 parts flaxseed oil, 15 parts perilla seed oil, 26 parts safflower seed oil, 22 parts olive oil, 3 parts sesame oil, 5 parts phytosterol esters, 0.5 parts sesame lignans, and 0.1 parts natural vitamin E. The mass ratio of sesame lignans to phytosterol esters is 0.5:5 = 1:10. GC analysis, based on the total fatty acid mass of the composition, shows that the mass fraction of ω-6 polyunsaturated fatty acids is 30.6%, and the mass fraction of ω-3 polyunsaturated fatty acids is 25.4%, with a mass ratio of 1.2:1. The saturated fatty acid content is 10.0%, the monounsaturated fatty acid content is 29.3%, and the polyunsaturated fatty acid content is 60.7%. HPLC analysis shows that the γ-tocotrienol content is 40 mg / 100g.

[0061] The composition of this embodiment was prepared using the same method as in Example 1, except that the stirring temperature was adjusted to 25°C and the stirring time to 60 min in step S4. The composition obtained in this embodiment is a clear and transparent oily liquid, which showed no stratification or precipitation after standing at room temperature for 90 days, and its quality remained stable.

[0062] Example 3

[0063] This embodiment provides a compound plant oil composition for regulating blood lipids, which differs from Example 1 only in the proportions of its components. Based on a total composition mass of 100 parts, the contents of each component are as follows: 30.43 parts flaxseed oil, 5 parts perilla seed oil, 30 parts safflower seed oil, 25 parts olive oil, 8 parts sesame oil, 1.5 parts phytosterol esters, 0.05 parts sesame lignans, and 0.02 parts natural vitamin E. The mass ratio of sesame lignans to phytosterol esters is 0.05:1.5 = 1:30. GC analysis, based on the total fatty acid mass in the composition, shows that the mass fraction of ω-6 polyunsaturated fatty acids in the composition is 33.9%, the mass fraction of ω-3 polyunsaturated fatty acids is 19.4%, and the mass ratio of the two is 1.7:1; the saturated fatty acid content is 10.5%, the monounsaturated fatty acid content is 31.6%, and the polyunsaturated fatty acid content is 57.9%. HPLC analysis shows that the γ-tocotrienol content is 10 mg / 100g (this example is a boundary example with low active component addition; the γ-tocotrienol content is less than 30 mg / 100g, which does not fall within the scope defined by claim 3, but it still falls within the scope of claim 2, and is used to illustrate the boundary feasibility of the formulation range of the present invention).

[0064] The composition of this embodiment was prepared using the same method as in Example 1, except that the stirring temperature was adjusted to 35°C and the stirring time to 30 min in step S4, and the homogenization pressure was adjusted to 20 MPa and homogenization was performed once in step S5. The composition obtained in this embodiment is a clear and transparent oily liquid, which showed no stratification or precipitation after standing at room temperature for 90 days, and its quality remained stable.

[0065] Example 4

[0066] This embodiment provides a compound plant oil self-microemulsifying soft capsule formulation for regulating blood lipids.

[0067] Take 60 parts of the composite vegetable oil composition prepared in Example 1, 20 parts of medium-chain triglycerides (MCT, carbon chain C8-C10), 15 parts of polysorbate 80 (Tween 80), and 5 parts of polyglycerol ricinoleate. Mix them at 100 r / min for 30 min under dark conditions at 30°C to obtain a uniform self-microemulsifying oil phase (where the total amount of hydrophilic surfactant is 20 parts, and the mass ratio of composition: medium-chain triglycerides: hydrophilic surfactant is 60:20:20, which meets the requirements of 55-75). The self-microemulsified oil phase was placed in a rotary evaporator and degassed for 20 minutes at 35°C and a vacuum of 0.06 MPa to remove air bubbles. Then, a conventional soft capsule pressing process was used to prepare soft capsule shells with gelatin, glycerin, purified water and caramel coloring (mass ratio 100:35:100:1). The degassed self-microemulsified oil phase was pressed into soft capsules with a content of 0.8 g per capsule. After shaping, drying and sorting, the compound vegetable oil self-microemulsified soft capsule formulation was obtained.

[0068] 0.5 g of the contents of the self-microemulsifying soft capsules were added to 50 mL of simulated gastric juice (pH 1.2, containing pepsin) at 37°C. The mixture was stirred at 50 r / min, and a Malvern laser particle size analyzer was used to determine that the formulation spontaneously formed a microemulsion with an average particle size of 86 nm (Particle size distribution PDI = 0.13) within 3 min. Similarly, in simulated intestinal juice (pH 6.8, containing pancreatic lipase and bile salts), the formulation spontaneously formed a microemulsion with an average particle size of 102 nm within 5 min. This indicates that the formulation of the present invention has excellent self-microemulsifying properties, significantly increasing the oil-water interface area, which is beneficial for the emulsification, hydrolysis, and absorption of lipid-soluble active ingredients.

[0069] Example 5

[0070] This embodiment provides a compound plant oil microcapsule powder formulation for regulating blood lipids.

[0071] Take 55 parts of the compound vegetable oil composition prepared in Example 2, 15 parts of medium-chain triglycerides, 15 parts of sucrose fatty acid esters, and 15 parts of maltodextrin, mix them evenly, add an appropriate amount of purified water, and emulsify them for 10 minutes at 60℃ and 8000r / min using a high-speed shear emulsifier to obtain a pre-emulsion. Send the pre-emulsion into a spray drying tower (inlet air temperature 170℃, outlet air temperature 85℃, feed flow rate 20mL / min), and collect the powder after spray drying. Pass it through a 60-mesh sieve to obtain the compound vegetable oil microcapsule powder (wherein the mass ratio of the composition: medium-chain triglycerides: hydrophilic surfactant is 55:15:15). This microcapsule powder has a moisture content of 3.2% and an encapsulation rate of 91.5%. It can be further compressed into tablets or directly packaged into bagged reconstituted powder. After reconstitution, it forms a stable oil-in-water emulsion with a delicate taste and no greasy feeling.

[0072] Example 6: Antioxidant Stability Test

[0073] The oxidation induction period of the compositions prepared in Examples 1-3 and the control samples was determined using a Rancimat 743 oil oxidation stability tester according to the method specified in GB / T21121. The control samples were set as follows: Control A was commercially available ordinary soybean oil blend (without sesame lignans and phytosterol esters); Control B was a composition prepared according to the proportions of Example 1 but without the addition of sesame lignans (containing only 0.2 parts of natural vitamin E); Control C was a composition prepared according to the proportions of Example 1 but without the addition of natural vitamin E (containing only 0.3 parts of sesame lignans). The measurement temperature was 120℃, and the air flow rate was 20 L / h. The results are shown in Table 1.

[0074] Table 1 Results of oxidation induction period determination for each sample

[0075] sample Oxidation induction period (h) Increase in magnitude compared to control A Example 1 Composition 9.8 +96.0% Example 2 Composition 8.7 +74.0% Example 3 Composition 7.9 +58.0% Compare with A (commercially available blended oil) 5.0 — Control B (without sesame lignans) 6.5 +30.0% Control C (without Vitamin E) 5.9 +18.0%

[0076] As shown in Table 1, the oxidation induction period of the compositions of Examples 1-3 was significantly longer than that of Control A. Compared with Control B (6.5 h) which only added vitamin E and Control C (5.9 h) which only added sesame lignans, the oxidation induction period of the composition of Example 1 (9.8 h) was significantly longer than the theoretical expectation of the simple sum of the effects of the two (6.5 + 5.9 - 5.0 = 7.4 h), indicating that there is a synergistic antioxidant effect between sesame lignans and natural vitamin E, rather than a simple sum. Furthermore, the composition of Example 1 was stored at 25°C in the dark for 12 months, and the peroxide value was measured to be 4.2 mmol / kg and the acid value was 1.1 mg KOH / g, both of which meet the requirements of GB2716 "National Food Safety Standard for Vegetable Oils" (peroxide value ≤ 5 mmol / kg, acid value ≤ 3 mg KOH / g), indicating that the composition of the present invention has excellent shelf-life stability.

[0077] Example 7: Animal lipid-lowering experiment

[0078] A hyperlipidemia model was established using male SD rats to investigate the lipid-lowering effect of the composition of the present invention and the synergistic effect of phytosterol esters and sesame lignans.

[0079] Experimental Methods: Ninety SPF-grade male SD rats weighing 180–220 g were selected and, after one week of acclimatization, were randomly divided into nine groups of ten rats each: blank control group (normal diet), model group (high-fat diet: 78.8% basal diet + 10% lard + 10% egg yolk powder + 1% cholesterol + 0.2% sodium cholate), positive control group (high-fat diet + simvastatin 5 mg / kg·d by gavage), Example 1 group, Example 2 group, Example 3 group, Comparative Example D1 group (high-fat diet + composition containing only 4.5 parts of phytosterol esters, without sesame lignans), Comparative Example D2 group (high-fat diet + composition containing only 0.3 parts of sesame lignans, without phytosterol esters), and Comparative Example D3 group (high-fat diet + composition containing 2.25 parts of phytosterol esters and 0.15 parts of sesame lignans, with a mass ratio of 1:15, and the total amount of active ingredients added is about half that of Example 1). All compositions were administered orally at a dose of 2.0 g / kg / day for 6 consecutive weeks. After the last administration, patients fasted for 12 hours, and blood was collected from the orbital venous plexus. Serum was separated, and serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using a fully automated biochemical analyzer. The results are shown in Table 2 (values ​​are expressed as mean ± SD).

[0080] Table 2. Serum lipid levels in rats of each group (mmol / L)

[0081] Group TC TG LDL-C HDL-C Blank control group 1.82±0.21 0.72±0.15 0.45±0.09 1.05±0.12 Model group 5.86±0.52 2.36±0.38 3.42±0.45 0.78±0.10 Positive control group 3.12±0.35 1.28±0.22 1.56±0.28 0.95±0.11 Example 1 Group 3.85±0.41 1.52±0.26 2.05±0.31 0.92±0.10 Example 2 group 4.02±0.44 1.60±0.28 2.18±0.35 0.90±0.11 Example 3 Group 4.18±0.46 1.68±0.30 2.30±0.38 0.88±0.10 Comparative Example D1 4.76±0.49 1.92±0.33 2.71±0.40 0.84±0.10 Comparative example D2 group 5.12±0.51 2.05±0.35 2.95±0.42 0.83±0.09 Comparative example D3 group 4.55±0.47 1.80±0.31 2.52±0.37 0.86±0.10

[0082] As shown in Table 2, compared with the model group, the serum TC, TG, and LDL-C levels of rats in Examples 1-3 were significantly decreased (P<0.01), while the HDL-C level was significantly increased (P<0.05). Among them, the TC, TG, and LDL-C levels in Example 1 were reduced by 34.3%, 35.6%, and 40.1% respectively compared with the model group, while the HDL-C level increased by 17.9%, which was close to the lipid-lowering level of simvastatin in the positive control group, but without the liver toxicity risk of simvastatin. In Comparative Example D1 (phytosterol esters only), the total TC (TC) decreased by 18.8% compared to the model group, and in Comparative Example D2 (sesame lignans only), the TC decreased by 12.6% compared to the model group. The sum of the TC reductions from the individual effects of these two groups was 31.4%. However, in Example 1 (phytosterol esters and sesame lignans were combined at a ratio of 1:15, with the total addition amount equivalent to D1+D2), the TC reduction reached 34.3%, significantly higher than the theoretical sum of the individual effects of the two groups (P<0.05). This demonstrates that phytosterol esters and sesame lignans have a significant synergistic lipid-lowering effect within a mass ratio range of 1:5 to 1:30. Furthermore, the TC reduction in Comparative Example D3 (total active ingredients halved) (22.4%) was significantly lower than that in Example 1 (34.3%), further illustrating that the synergistic effect of the active ingredients in this invention at specific ratios depends on the sufficient addition and reasonable ratio of the active ingredients.

[0083] Example 8: Bioavailability Test

[0084] The bioavailability of phytosterol esters in the microemulsion soft capsule formulation of this invention was investigated using male SD rats.

[0085] Experimental Methods: Twenty male SD rats weighing 220–260 g were randomly divided into two groups of 10 each: the experimental group (administered via gavage with the contents of self-microemulsified soft capsules prepared in Example 4, at a dose of 30 mg / kg phytosterol esters) and the control group (administered via gavage with the contents of ordinary soft capsules directly filled with the composition of Example 1, at a dose of 30 mg / kg phytosterol esters). Blood samples were collected from the orbital sinus at 0, 1, 2, 4, 6, 8, 12, and 24 hours after administration. The concentration of free phytosterols (total β-sitosterol + campesterol + stigmasterol) in serum was determined by GC-MS, and pharmacokinetic parameters were calculated. The results are shown in Table 3.

[0086] Table 3 Results of Pharmacokinetic Parameter Determination of Phytosterols

[0087] parameter Experimental group (self-microemulsifying soft capsules) Control group (regular soft capsules) Cmax (μg / mL) 6.82±0.71 3.21±0.45 Tmax(h) 3.2±0.5 5.6±0.8 AUC0-24h (μg·h / mL) 58.6±6.3 29.3±4.1 24-hour cumulative absorption (μg) 412±45 182±26

[0088] As shown in Table 3, the Cmax of serum phytosterols in the experimental group rats was 2.13 times higher than that in the control group, the Tmax was 2.4 h earlier, the AUC0-24h was 2.0 times higher, and the cumulative absorption in 24h was 2.26 times higher. This indicates that the self-microemulsified formulation of the present invention can significantly improve the absorption rate and total absorption of phytosterol esters in vivo, thereby enhancing its pharmacological effect of inhibiting cholesterol absorption in the intestine.

[0089] Example 9: Comparison Experiment of ω-6 / ω-3 Ratio

[0090] The effect of the mass ratio of ω-6 to ω-3 polyunsaturated fatty acids in the composition on the lipid-lowering effect was investigated.

[0091] Based on the formulation of Example 1 (the total mass of the oil phase remained at 95 parts, of which 22 parts were olive oil and 8 parts were sesame oil; the active components remained at 4.5 parts of phytosterol esters, 0.3 parts of sesame lignans and 0.2 parts of natural vitamin E), only the ratio of flaxseed oil, perilla seed oil and safflower seed oil was adjusted (the sum of flaxseed oil and perilla seed oil was a+b parts, and safflower seed oil was 65-ab parts), and seven compositions with an ω-6 / ω-3 mass ratio of approximately 1.2:1, 1.7:1, 2:1, 3:1, 4:1, 6:1 and 9:1 were prepared, and the total polyunsaturated fatty acid content in each composition was kept to be basically the same (55% to 62%). The compositions with ω-6 / ω-3 ratios of 1.2:1 and 1.7:1 correspond to the ratios in Examples 2 and 1, respectively. Compositions with ω-6 / ω-3 ratios of 3:1, 4:1, 6:1, and 9:1 were achieved by partially substituting flaxseed oil and perilla seed oil with safflower seed oil (e.g., when ω-6 / ω-3 is 4:1, approximately 14.3 parts flaxseed oil, 5 parts perilla seed oil, and approximately 45.7 parts safflower seed oil). The compositions with ratios of 6:1 and 9:1 exceed the 1:1 to 4:1 range defined in claim 1 and are used only as comparative samples. A lipid-lowering experiment was conducted in rats (n=10 per group) according to the method in Example 7, and the serum TG and TC levels of each group of rats were measured. The results are shown in Table 4.

[0092] Table 4. Comparison of lipid-lowering effects of compositions with different ω-6 / ω-3 ratios.

[0093] Composition (ω-6 / ω-3) TG reduction compared to the model group TC reduction compared to the model group 1.2:1 (corresponding to Example 2) 32.2% 31.4% 1.7:1 (corresponding to Example 1) 35.6% 34.3% 2:1 34.1% 33.5% 3:1 30.5% 29.8% 4:1 27.5% 26.9% 6:1 (comparison) 17.4% 19.2% 9:1 ​​(comparison) 12.3% 14.5%

[0094] As shown in Table 4, when the ω-6 / ω-3 mass ratio is in the range of 1:1 to 4:1, the composition exhibits significantly better TG and TC reduction effects (TG reduction of more than 27.5%). When the ω-6 / ω-3 mass ratio increases to above 6:1, the lipid-lowering effect significantly decreases (TG reduction of less than 20%). Among these, the lipid-lowering effect is optimal when the ω-6 / ω-3 mass ratio is between 1.5:1 and 3:1 (TG reduction of 30.5% to 35.6%). This indicates that the precise control of the mass ratio of ω-6 and ω-3 polyunsaturated fatty acids in this invention is one of the key technical features for achieving excellent lipid-lowering effects. This ratio feature, together with the synergistic combination of phytosterol esters and sesame lignans, constitutes the complete technical solution of this invention.

[0095] Example 10: Human Trial

[0096] Sixty volunteers with borderline elevated blood lipids (serum TC 5.2–6.2 mmol / L) were randomly divided into two groups of 30 each: a trial group (consuming 10 mL of the composition from Example 1 with lunch and dinner daily for 8 weeks) and a placebo group (consuming an equal amount of refined soybean oil with meals daily for 8 weeks). Participants maintained their original dietary habits during the trial and did not take any other lipid-lowering drugs or health supplements. Results: After 8 weeks, serum TC in the experimental group decreased from 5.86±0.35 mmol / L before the experiment to 5.12±0.42 mmol / L (a decrease of 12.6%, P<0.05), TG decreased from 1.98±0.41 mmol / L to 1.62±0.38 mmol / L (a decrease of 18.2%, P<0.05), LDL-C decreased from 3.45±0.52 mmol / L to 3.02±0.48 mmol / L (a decrease of 12.5%, P<0.05), and HDL-C increased from 1.12±0.21 mmol / L to 1.21±0.22 mmol / L (an increase of 8.0%, P<0.05). In the placebo group, none of the indicators showed significant changes (P>0.05). No adverse events occurred in either group during the experiment, and liver and kidney function indicators remained within the normal range, indicating that the composition of this invention has good safety and auxiliary lipid-regulating effects.

[0097] Example 11: Verification Experiment of Preparation Process Parameters

[0098] To verify the feasibility of the process parameter ranges in the preparation method of the present invention, based on the proportions of Example 1, different combinations of process conditions were selected within the parameter range defined in claim 7 for preparation, and the quality of the resulting compositions was examined. Specific combinations of process conditions and results are shown in Table 5.

[0099] Table 5. Quality evaluation results of the compositions under different process conditions

[0100] Test No. S3 dissolution temperature (°C) S4 Stirring Temperature / Time (°C / min) S5 Homogenization Pressure / Number of Cycles (MPa / cycle) Deviation in active ingredient content 90-day stability Peroxide value (mmol / kg) 1 65 25 / 60 20 / 1 4.2% No layering, no sedimentation 1.1 2 70 30 / 45 30 / 2 2.8% No layering, no sedimentation 0.8 3 75 35 / 30 40 / 3 3.5% No layering, no sedimentation 1.0 4 (Comparison) 60 30 / 45 30 / 2 8.6% A small amount of flocculent precipitate 1.6 5 (Comparison) 80 30 / 45 30 / 2 6.9% No layering 2.3

[0101] As shown in Table 5, within the parameter range defined in claim 7 (tests 1-3), the deviation of the active ingredient content in the obtained compositions is less than 5%, with no stratification or precipitation after 90 days of standing, and the peroxide value is no higher than 1.1 mmol / kg, indicating excellent quality and good batch-to-batch consistency. However, when the dissolution temperature of S3 is below 65℃ (test 4, 60℃), the phytosterol esters are not completely dissolved, resulting in flocculent precipitates and increased deviation in the active ingredient content. When the dissolution temperature of S3 is above 75℃ (test 5, 80℃), the peroxide value increases significantly, and oxidation loss intensifies. This indicates that the limitation of the range of process parameters in the preparation method of the present invention has a synergistic effect on ensuring the quality of the compositions, which cannot be easily determined through inventive effort.

[0102] Example 12: Formulation stability and sensory evaluation test

[0103] Accelerated stability tests and sensory evaluations were conducted on the self-microemulsifying soft capsules prepared in Example 4. The soft capsules were placed in constant temperature and humidity chambers at 40℃ / 75%RH (accelerated conditions) and 25℃ / 60%RH (long-term conditions), respectively. Samples were taken periodically to test the peroxide value, phytosterol ester content, and disintegration time of the contents. The results are shown in Table 6.

[0104] Table 6. Results of stability tests on self-microemulsifying soft capsules

[0105] Storage conditions Time (month) Peroxide value (mmol / kg) Phytosterol ester content (g / capsule) Disintegration timeout (min) initial 0 0.8 0.108 18 25℃ / 60%RH 6 1.5 0.106 19 25℃ / 60%RH 12 2.3 0.105 21 40℃ / 75%RH 3 2.1 0.104 20 40℃ / 75%RH 6 3.6 0.102 22

[0106] As shown in Table 6, after 6 months of accelerated storage at 40℃ / 75%RH, the peroxide value of the self-microemulsified soft capsules increased from 0.8 mmol / kg to 3.6 mmol / kg, still meeting the requirements of GB2716 (≤5 mmol / kg). The phytosterol ester content retention rate was 94.4%, and the disintegration time was less than 30 min, meeting the requirements of the Chinese Pharmacopoeia for the disintegration time of soft capsules. After 12 months of long-term storage at 25℃ / 60%RH, all indicators remained good. Sensory evaluation (10-person group, scores 1-5 points) showed that the self-microemulsified soft capsules of this invention had a smooth appearance, no content precipitation, no off-odor, and a taste score of 4.6 points, indicating good acceptability.

[0107] Example 13: Comparison of Sesamin to Sesamol Ratio

[0108] To verify the limitation of the scope of "the mass ratio of sesamin to sesamol is 3:1 to 10:1" in claim 6, based on the formulation of Example 1, only the mass ratio of sesamin to sesamol in the sesame lignan extract was changed, and five compositions with sesamin:sesol ratios of 2:1, 3:1, 6:1 (used in Example 1), 10:1, and 15:1 were prepared. All other components and process conditions were the same as in Example 1. A lipid-lowering test was conducted in rats (n=10 per group) according to the method of Example 7 to examine the reduction of serum total cholesterol (TC) and the inhibition rate of hepatic HMG-CoA reductase activity by each composition. The results are shown in Table 7.

[0109] Table 7 Comparison of lipid-lowering effects of compositions with different sesamin / sesamol ratios

[0110] Composition (sessamin: sesamol) TC reduction compared to the model group HMG-CoA reductase activity inhibition rate 2:1 (comparison) 28.6% 31.2% 3:1 32.8% 38.5% 6:1 (Example 1) 34.3% 42.1% 10:1 33.1% 39.8% 15:1 (comparison) 29.4% 33.6%

[0111] As shown in Table 7, when the mass ratio of sesamin to sesamol is within the range of 3:1 to 10:1, the reduction in TC (32.8%–34.3%) and the inhibition rate of hepatic HMG-CoA reductase activity (38.5%–42.1%) of the composition are significantly better than those of the control samples outside the range (28.6% and 31.2% at 2:1, and 29.4% and 33.6% at 15:1, respectively). This indicates that when sesamin and sesamol are combined in a mass ratio of 3:1 to 10:1, they can exert the optimal synergistic effect in the "inhibition of endogenous cholesterol synthesis" stage, and this ratio range is one of the key technical features of this invention.

[0112] Example 14: Comparative Experiment on Esterification Rate of Phytosterol Esters

[0113] To verify the limitation in claim 5 that "the esterification rate of phytosterol esters is not less than 95%", the formulation of Example 1 was used as a basis, only the phytosterol esters with different esterification rates were changed (esterification rates of 88%, 92%, 95%, and 97%, respectively), while the other components and process conditions remained the same as in Example 1. The dissolution time of the phytosterol esters in each composition during the S3 pre-dispersion process (based on the condition that the mixture is clear and transparent with no visible particles) and the precipitation of the obtained compositions after standing at room temperature for 90 days were investigated. The results are shown in Table 8.

[0114] Table 8. Results of the dispersibility study of phytosterol esters with different esterification rates

[0115] esterification rate of phytosterol esters S3 dissolution time (min) Precipitation after 90 days of standing 88% (comparison) 65 A small amount of white needle-like precipitate 92% (comparison) 50 Trace precipitates 95% 32 No precipitation 97% 25 No precipitation

[0116] As shown in Table 8, when the esterification rate of phytosterol esters is not less than 95%, they can be completely dissolved within 35 minutes in the S3 pre-dispersion process, and the resulting composition shows no precipitation after 90 days of standing. However, when the esterification rate is less than 95%, the content of free phytosterols is high, the dissolution time is significantly prolonged, and precipitation occurs after long-term standing, affecting the appearance of the composition and the uniformity of the active ingredients. This indicates that the limitation on the esterification rate of phytosterol esters in claim 5 is of great significance for ensuring the dispersion stability of the composition. In addition, the phytosterol esters selected in this invention contain not less than 50% β-sitosterol esters and are compounded with campesterol esters and stigmasterol esters. On the one hand, this ensures a competitive inhibitory effect similar to cholesterol in structure; on the other hand, the combination of multiple sterol esters can increase their total solubility in the oil phase. The β-sitosterol esters used in Examples 1 and 2 contain 56% and 53% β-sitosterol esters, respectively, and the total contents of campesterol esters and stigmasterol esters are 38% and 41%, respectively, all of which meet the limitations of claim 5.

[0117] Example 15: Comparative Test with Representative Existing Formulas

[0118] To further illustrate the technological advancements of this invention, Comparative Example E1 was prepared according to the formulation of Example 1 disclosed in Chinese Patent Application CN113973929A (30 kg corn germ oil, 35 kg flaxseed oil, 5 kg sesame oil, 2 kg phytosterols, 28 kg soybean oil, stirred at 50°C for 1 hour); Comparative Example E2 was prepared according to the proportions disclosed in Chinese Patent Application CN103284151A (500 parts sunflower seed oil, 250 parts grape seed oil, 150 parts black sesame oil, 150 parts perilla oil, 5 parts perilla volatile oil, 5 parts sesame lignans, mixed together); and Comparative Example E3 was prepared according to the proportions disclosed in Chinese Patent Application CN115281250A (15 parts flaxseed oil, 10 parts safflower seed oil, 60 parts sunflower seed oil, 0.4 parts vitamin E, 8 parts walnut oil, 6 parts tea seed oil, 15 parts perilla oil, 6 parts olive oil, 6 parts sesame oil, refined). Using the composition of Example 1 as the test group, a lipid-lowering rat test was conducted in parallel with comparative examples E1 to E3 (the method was the same as in Example 7, with 10 rats in each group). The results are shown in Table 9.

[0119] Table 9 Comparison of lipid-lowering effects with representative formulations of existing technologies

[0120] sample TC reduction compared to the model group TG reduction compared to the model group Example 1 Composition 34.3% 35.6% Comparative Example E1 (according to CN113973929A) 24.6% 26.8% Comparative Example E2 (according to CN103284151A) 27.9% 29.5% Comparative Example E3 (according to CN115281250A) 22.8% 25.3%

[0121] As shown in Table 9, the reduction in TC and TG by the composition of Example 1 of the present invention was significantly higher than that of the comparative sample prepared according to the representative formula of the prior art (P<0.05). This indicates that the present invention has achieved a lipid regulation effect superior to the prior art through the synergistic combination of phytosterol esters and sesame lignans, the precise ratio of ω-6 / ω-3 fatty acids, and the synergistic effect of the preparation process.

[0122] The embodiments described herein are preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Therefore, all equivalent changes made in accordance with the structure, shape, and principle of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A compound vegetable oil composition for regulating blood lipids, characterized in that, The composition comprises an oil phase component and an active component; the oil phase component includes flaxseed oil, perilla seed oil, safflower seed oil, olive oil, and sesame oil; the active component includes phytosterol esters, sesame lignans, and natural vitamin E; the mass ratio of sesame lignans to phytosterol esters is 1:5 to 1:30; based on the mass of total fatty acids in the composition, the mass ratio of ω-6 polyunsaturated fatty acids to ω-3 polyunsaturated fatty acids in the composition is 1:1 to 4:

1.

2. The compound vegetable oil composition for regulating blood lipids according to claim 1, characterized in that, Based on a total mass of 100 parts of the composition, the content of each component is as follows: 25-45 parts of flaxseed oil, 5-20 parts of perilla seed oil, 10-30 parts of safflower seed oil, 10-25 parts of olive oil, 2-8 parts of sesame oil, 1.5-5 parts of phytosterol esters, 0.05-0.5 parts of sesame lignans, and 0.02-0.2 parts of natural vitamin E.

3. The compound vegetable oil composition for regulating blood lipids according to claim 2, characterized in that, The composition contains not less than 30 mg / 100g of γ-tocotrienol.

4. A compound vegetable oil composition for regulating blood lipids according to any one of claims 1 to 3, characterized in that, Based on the mass of total fatty acids in the composition, the content of saturated fatty acids in the composition is not higher than 12%, the content of monounsaturated fatty acids is 25% to 45%, the content of polyunsaturated fatty acids is 40% to 65%, and the mass ratio of ω-6 polyunsaturated fatty acids to ω-3 polyunsaturated fatty acids is 1.5:1 to 3:

1.

5. The compound vegetable oil composition for regulating blood lipids according to claim 1, characterized in that, The phytosterol ester contains at least 50% β-sitosterol ester by mass, with the remainder being at least one of campesterol ester and stigmasterol ester; the esterification rate of the phytosterol ester is at least 95%.

6. The compound vegetable oil composition for regulating blood lipids according to claim 1, characterized in that, The sesame lignans comprises sesamin and sesamol, wherein the mass ratio of sesamin to sesamol is 3:1 to 10:

1.

7. The method for preparing a compound vegetable oil composition for regulating blood lipids according to claim 1, characterized in that, Includes the following steps: S1. Raw material pretreatment: Flaxseed, perilla seed, safflower seed, olive fruit and sesame were pressed at low temperature to obtain flaxseed oil, perilla seed oil, safflower seed oil, olive oil and sesame oil. The peroxide value of each oil was not higher than 3 mmol / kg. S2. Weighing and mixing: Weigh each oil phase component and active component according to the composition ratio of the composition; S3. Pre-dispersion of active components: Plant sterol esters, sesame lignans and natural vitamin E are added to a mixture of sesame oil and olive oil and stirred at 65-75°C to dissolve them, thus obtaining an oil solution of active components. S4. Nitrogen-purified mixing: The active component oil solution is mixed with flaxseed oil, perilla seed oil and safflower seed oil under nitrogen protection conditions, and stirred at 25-35℃ and 60-120r / min for 30-60min to obtain the mixed oil. S5. High-pressure homogenization: The mixed oil is homogenized 1 to 3 times under a pressure of 20 to 40 MPa to obtain homogenized oil; S6. Cooling and degassing: Cool the homogenized oil to below 20°C and perform vacuum degassing; S7. Quality Inspection: The fatty acid composition, phytosterol ester content, sesame lignan content, peroxide value, and mass ratio of ω-6 to ω-3 polyunsaturated fatty acids in the homogenized oil are tested. If the results are qualified, the composite vegetable oil composition is obtained. S8. Filling: Fill and seal the qualified compound vegetable oil composition.

8. A self-microemulsifying compound plant oil preparation for regulating blood lipids, characterized in that, The formulation comprises a lipid-regulating compound vegetable oil composition according to any one of claims 1 to 6, a medium-chain triglyceride, and a hydrophilic surfactant; the mass ratio of the compound vegetable oil composition, the medium-chain triglyceride, and the hydrophilic surfactant is 55-75:10-25:15-30; the formulation spontaneously emulsifies upon contact with water or gastrointestinal fluid to form a microemulsion with an average particle size of no more than 200 nm.

9. A compound vegetable oil self-microemulsifying preparation according to claim 8, characterized in that, The hydrophilic surfactant is selected from at least one of polysorbate 80, polyglycerol ricinoleate, and sucrose fatty acid ester; the formulation is a soft capsule or a microcapsule powder.

10. The use of a compound vegetable oil composition for regulating blood lipids according to any one of claims 1 to 6, or a compound vegetable oil self-microemulsifying preparation according to any one of claims 8 to 9, in the preparation of health foods, special medical purpose formula foods, or functional edible oils that assist in regulating blood lipids.

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