Hypolipidemic composition containing supramolecular group composite peptide and application of hypolipidemic composition in functional food and medicine

Abstract

The invention discloses a blood fat reducing composition containing supramolecular group composite peptide, which is composed of raw materials and basic energy substrates, the raw materials comprise supramolecular group composite peptide, natto freeze-dried powder, black pepper extract and bamboo leaf flavone, and the basic energy substrates comprise proteins, dietary fibers, fatty acids and / or lipids; the composite peptide is composed of soybean peptide and bitter gourd peptide. The composition prepared by compounding the components of specific types and dosages has the effects of remarkably reducing the triglyceride level, reducing the content of low-density lipoprotein cholesterol and increasing the content of high-density lipoprotein cholesterol, and part of the composition can also cooperate with statin western medicines (such as atorvastatin calcium) to achieve the effects of enhancing the effect of reducing blood fat and improving the blood fat content. The effect of assisting in improving or preventing and reducing blood fat is achieved. Therefore, the method can be used for developing functional foods and medicines and has a considerable market prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of the formula of a peptide-containing hypolipidemic composition, and in particular to a hypolipidemic composition containing a supramolecular group complex peptide and a preparation method thereof, and application of the composition in functional food and medicine for assisting in improving or preventing hyperlipidemia. BACKGROUND

[0002] With the improvement of living standards and the change of life rhythm, hyperlipidemia, as one of the "three high syndromes", has become a chronic disease that modern people are prone to suffer from. Hyperlipidemia, also known as hyperlipidemia or dyslipidemia, generally refers to the increase of triglyceride TG and / or total cholesterol TC in blood plasma, the increase of low-density lipoprotein cholesterol LDL-C and the decrease of high-density lipoprotein cholesterol HDL-C, and the deposition on the inner membrane of arteries, resulting in thickening and hardening of the arterial wall, narrowing of the lumen, and decrease of blood supply to the blood supply organs. With the high incidence of myocardial infarction and cerebral thrombosis caused by dyslipidemia, especially hypercholesterolemia, the family and social burden of such diseases is increasing, and has become a major public health problem. The disease can occur in people of different ages and genders, and is particularly common in people aged 50-69 years, with obvious genetic tendency. Studies have shown that the overall prevalence of dyslipidemia in Chinese adults is as high as 40.0%, and the causes of the disease include not only genetic inheritance, but also unhealthy eating habits, unhealthy living habits, lack of exercise, obesity, etc., and in recent years, the prevalence rate of the youth population has also increased significantly.

[0003] There are many drugs for treating hyperlipidemia in clinical practice at present, which generally include the following categories: statins (such as atorvastatin, atorvastatin calcium, etc.), cholesterol absorption inhibitors (such as ezetimibe, etc.), PCSK9 inhibitors (such as evolocumab, alirocumab, etc.), fibrates (such as fenofibrate, bezafibrate, etc.), among which the first-line drugs are mainly atorvastatin calcium or atorvastatin. As the saying goes, "every drug has some toxicity", these drugs for treating hyperlipidemia, regardless of the mechanism of action, will have some same or different adverse reactions, such as gastrointestinal irritation, potential liver and kidney toxicity risk caused by long-term use of western medicines for lowering blood lipids, etc.

[0004] Therefore, it is necessary to find some natural products, plant extracts or raw materials of medicinal and edible origin, and develop functional foods with certain hypolipidemic effect to assist in improving the triglyceride level of patients with hyperlipidemia, to reduce the dosage of western medicines for lowering blood lipids used by patients with hyperlipidemia to some extent, or to better regulate the triglyceride level while taking the same dosage of western medicines for lowering blood lipids, which has important social benefits.

[0005] Chinese patent application CN117256867A discloses a compound peptide powder for reducing three high and a preparation method thereof. The compound peptide powder comprises the following raw materials: soybean peptide, pea peptide, ginkgo biloba peptide, fish collagen peptide, corn oligopeptide, bitter gourd peptide, wheat oligopeptide, plant extract, modified quercetin, sweetener, modified chitosan, red yeast rice, and probiotic freeze-dried powder. The compound peptide powder has the functions of antioxidant, blood pressure reduction, cholesterol reduction, blood lipid reduction, anti-fatigue, and immune enhancement. The core of the technical solution is to realize the synergistic effect of reducing three high by adding modified quercetin and modified chitosan. The plant extract in the patent is derived from garland chrysanthemum and Gynostemma pentaphyllum.

[0006] Chinese patent application CN115299519A discloses a sugar candy containing ginseng stem cells for assisting in reducing blood lipids and a preparation method thereof. The sugar candy comprises ginseng stem cell freeze-dried powder, natto powder, milk powder, red yeast rice, small molecule plant peptide, acidity regulator, sugar or sweetener, lubricant, and other functional raw materials. The core of the technical solution is to realize the best effect of reducing blood lipids by adjusting the amount of ginseng stem cell freeze-dried powder. The small molecule plant peptide in the patent can be selected from one or more of soybean peptide, corn oligopeptide, wheat oligopeptide, pea peptide, walnut peptide, mung bean peptide, and bitter gourd peptide.

[0007] Chinese patent applications CN104621287A and CN109700024A both indicate that bitter gourd peptide has the effect of reducing blood sugar, but the existing technology has not reported that bitter gourd peptide has the effect of reducing blood lipids.

[0008] Through retrieval, no literature has reported that soybean peptide, bitter gourd peptide, natto freeze-dried powder, black pepper extract, and bamboo leaf flavonoids can be combined to form a composition with the effect of reducing blood lipids. Due to the huge differences in the physicochemical properties of the above-mentioned five components, it is uncertain whether the formed composition has a more optimal effect of reducing blood lipids compared with first-line blood lipid-lowering western medicine (statins such as atorvastatin calcium and atorvastatin). Further, it is also uncertain whether the combination of the composition and statin blood lipid-lowering western medicine can exert a synergistic effect.

[0009] In summary, how to develop a blood lipid-lowering composition different from the research framework of the existing technology, whose effect of reducing blood lipids can be comparable to or even better than that of first-line blood lipid-lowering western medicine (such as atorvastatin and atorvastatin calcium), and further explore a composition that can be used in combination with statin blood lipid-lowering western medicine to improve triglyceride levels synergistically, is a technical problem that has not been solved by researchers in the field. SUMMARY

[0010] The first invention of the present application is to provide a specific hypolipidemic composition, which has clear functional material components and appropriate mass ratio of each functional material component to ensure that the composition has a significant effect of improving triglyceride level; further, the hypolipidemic effect of the composition is superior to that of statins.

[0011] The second invention of the present application is to provide a hypolipidemic composition containing specific component types and use amount ratios, which can be used in combination with statins to coordinate and synergize, and the hypolipidemic effect of the combination is superior to that of the composition alone or statins alone.

[0012] To achieve the above-mentioned invention purposes of the present application, the following technical solutions are adopted.

[0013] The present application provides a hypolipidemic composition containing a supermolecular group complex peptide, which is composed of raw materials and basic energy substrates, wherein the basic energy substrates include protein, dietary fiber, fatty acid and / or lipid; the raw materials include complex peptide, freeze-dried powder of naotou, black pepper extract and bamboo leaf flavone, and the complex peptide is composed of soybean peptide and momordica charantia peptide.

[0014] Preferably, in the complex peptide contained in the composition, the mass ratio of soybean peptide to momordica charantia peptide is (1:1)~(5:3).

[0015] More preferably, in the complex peptide contained in the composition, the mass ratio of soybean peptide to momordica charantia peptide is 1:1.

[0016] More preferably, in the complex peptide contained in the composition, the mass ratio of soybean peptide to momordica charantia peptide is 5:3.

[0017] Preferably, in the composition, the mass ratio of complex peptide to black pepper extract is (25:1)~(100:1).

[0018] More preferably, in the composition, the mass ratio of complex peptide to black pepper extract is 100:1.

[0019] The present application also provides a hypolipidemic composition, which contains the following components in the raw materials in the following amounts: 0.5~2.5 mass parts of soybean peptide, 0.5~1.5 mass parts of momordica charantia peptide, 0.03~0.25 mass parts of freeze-dried powder of naotou, 0.01~0.04 mass parts of black pepper extract and 0.12~0.5 mass parts of bamboo leaf flavone.

[0020] Preferably, in the composition, the mass ratio of complex peptide to black pepper extract is (25:1)~(100:1).

[0021] Preferably, the raw materials of the composition include the following components in the following amounts: 0.5 parts by weight of soybean peptide, 0.5 parts by weight of bitter melon peptide, 0.03 parts by weight of natto freeze-dried powder, 0.01 parts by weight of black pepper extract, and 0.12 parts by weight of bamboo leaf flavonoids.

[0022] Preferably, the raw materials of the composition include the following components in the following amounts: 2.5 parts by weight of soybean peptide, 1.5 parts by weight of bitter melon peptide, 0.12 parts by weight of natto freeze-dried powder, 0.04 parts by weight of black pepper extract, and 0.48 parts by weight of bamboo leaf flavonoids.

[0023] Preferably, the raw materials of the composition include the following components in the following amounts: 2.5 parts by weight of soybean peptide, 0.5 parts by weight of bitter melon peptide, 0.09 parts by weight of natto freeze-dried powder, 0.03 parts by weight of black pepper extract, and 0.36 parts by weight of bamboo leaf flavonoids.

[0024] Preferably, the raw materials of the composition include the following components in the following amounts: 0.5 parts by weight of soybean peptide, 0.5 parts by weight of bitter melon peptide, 0.03 parts by weight of natto freeze-dried powder, 0.04 parts by weight of black pepper extract, and 0.12 parts by weight of bamboo leaf flavonoids.

[0025] In this invention, the basic energy substrate contained in the aforementioned composition, The protein is selected from one or more of the following: whey protein concentrate, soy protein isolate, yeast protein, pea protein, casein, and lactoferrin. Dietary fiber is selected from one or more of the following: pectin cellulose, L-arabinose, chitosan, yeast β-glucan, fucoidan, galactooligosaccharide, galactomannan, fructooligosaccharide, xylooligosaccharide, inulin, polydextrose, isomaltulose, resistant dextrin, stachyose, and psyllium husk powder. Fatty acids and / or lipids are selected from one or more of DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), diglycerides, medium-chain triglycerides, medium- and long-chain triglycerides, palm kernel oil, egg yolk lecithin, soybean lecithin, olive oil powder, sunflower seed oil powder, and fish oil powder.

[0026] The third objective of this invention is to provide an application of the above-mentioned composition in the development of pharmaceuticals and functional foods, wherein the developed pharmaceuticals and functional foods can be used to prevent or improve hyperlipidemia, and can be prepared into various formulations.

[0027] To achieve the third objective of this invention, the following technical solution is adopted.

[0028] The use of the composition as described above in the preparation of pharmaceuticals and functional foods related to the prevention or improvement of hyperlipidemia.

[0029] Furthermore, this drug and functional food can lower the triglyceride level in zebrafish, or reduce the content of low-density lipoprotein cholesterol (LDL-C) in zebrafish, or increase the content of high-density lipoprotein cholesterol (HDL-C) in zebrafish.

[0030] Furthermore, the drug comprises the composition as described above and a pharmaceutically acceptable carrier.

[0031] Specifically, pharmaceutically acceptable carriers include diluents, excipients, fillers, emulsifiers, binders, lubricants, absorption enhancers, surfactants, disintegrants, or antioxidants commonly used in the pharmaceutical field. Furthermore, pharmaceutically acceptable carriers may also include, but are not limited to, flavoring agents, sweeteners, preservatives, or coloring agents. Examples include: sorbitol, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, soybean lecithin, vitamin C, vitamin E, disodium EDTA, carbonates, acetates, phosphates or aqueous solutions of monovalent alkali metals, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acids, sodium chloride, potassium chloride, sodium lactate, ethylparaben solution, benzoic acid, potassium sorbate, chlorhexidine acetate, maltose, glucose, dextran, starch, sucrose, lactose, mannitol, cellulose and its derivatives, alginate, gelatin, polyvinylpyrrolidone, glycerol, Tween 80, agar, calcium carbonate, calcium bicarbonate, polyethylene glycol, cyclodextrin, phospholipids, kaolin, talc, calcium stearate or magnesium stearate, etc.

[0032] The compositions provided by the present invention can be administered via gastrointestinal or non-gastrointestinal routes.

[0033] The term "gastrointestinal administration" refers to dosage forms that enter the gastrointestinal tract after oral administration and exert local or systemic effects through absorption, such as powders, granules, films, tablets, granules, capsules, solutions, emulsions, suspensions, syrups, and pills.

[0034] The term "non-gastrointestinal administration" refers to all dosage forms other than oral administration. These dosage forms exert local effects at the administration site or systemic effects after absorption. They mainly include injectable dosage forms, respiratory dosage forms, transdermal dosage forms, mucosal dosage forms, and cavity dosage forms. Further classifications are as follows: (1) Injectable dosage forms: such as injections, including intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection and intracavitary injection, etc.; (2) Respiratory drug delivery formulations: such as sprays, aerosols, powder inhalers, etc.; (3) Dermal drug delivery formulations: such as topical solutions, lotions, liniments, ointments, plasters, pastes, patches, etc.; (4) Mucosal drug delivery dosage forms: such as eye drops, nasal drops, ointments, mouthwashes, sublingual tablets, adhesive patches and films, etc.; (5) Intracavitary drug delivery dosage forms: such as suppositories, aerosols, effervescent tablets, drops and pills, etc., for use in the rectum, vagina, urethra, nasal cavity, ear canal, etc.

[0035] The preferred route of administration for the composition provided by the present invention is gastrointestinal administration.

[0036] Preferably, the dosage form of the drug or functional food is selected from one of solid dosage forms, liquid dosage forms, semi-solid dosage forms, and gaseous dosage forms.

[0037] Furthermore, the dosage form of the drug or functional food can be either an oral solid dosage form or an oral liquid dosage form.

[0038] Preferably, the oral solid dosage form is selected from powder, granule, film, tablet, granule, capsule or drop.

[0039] Preferably, the oral liquid formulation is selected from suspensions, solutions, emulsions or syrups.

[0040] In the prescription of this invention, the dosage of the extracts and their active ingredients depends on factors such as the age, weight, and type and severity of the disease of the target patient.

[0041] Compared with the prior art, the lipid-lowering composition provided by the present invention has the following beneficial effects: This invention, by selecting specific types and amounts of active ingredients as raw materials and combining them to form a composition, significantly reduces triglyceride levels, decreases low-density lipoprotein cholesterol (LDL-C) content, and increases high-density lipoprotein cholesterol (HDL-C) content. It exhibits significant efficacy in a lipid-lowering zebrafish model, demonstrating a good lipid-lowering effect. Furthermore, when the mass ratio of the complex peptide to black pepper extract and the mass ratio of soybean peptide to bitter melon peptide in the composition are controlled, the resulting lipid-lowering composition (such as Composition A), when used in combination with statins (such as atorvastatin calcium), shows superior efficacy in the lipid-lowering zebrafish model compared to using statins alone or the composition provided by this invention alone. This means that the lipid-lowering composition (such as Composition A) provided by this invention, when used in combination with statins, can have a significant synergistic effect in lowering blood lipids.

[0042] Therefore, the lipid-lowering composition provided by this invention has market value as a pharmaceutical or functional food. Attached Figure Description

[0043] Figure 1 This is an evaluation of the lipid-lowering efficacy of each experimental group in Example 8.

[0044] Note: Compared with the model control group, * p < 0.05, **p < 0.01, *** p < 0.001; compared with the positive control group, # p < 0.05, ## p < 0.01, ### p < 0.001.

[0045] Figure 2 Typical images of triglyceride staining intensity in the blood vessels of zebrafish tails in each experimental group of Example 8.

[0046] Note: Figure 2 The example image in the diagram illustrates the analysis site, and the analysis area (dashed line) refers to the blood vessels in the zebrafish tail.

[0047] Figure 3 This is an evaluation of the lipid-lowering efficacy of the combination of the composition in Example 9 with the positive control drug.

[0048] Note: Compared with the model control group, * p < 0.05, ** p < 0.01, *** p < 0.001; compared with the positive control group, # p < 0.05, ## p < 0.01, ### p < 0.001; compared with composition E, ☆ p < 0.05, ☆☆ p < 0.01, ☆☆☆ p <0.001; compared with composition B, △ p < 0.05, △△ p < 0.01, △△△ p < 0.001; compared with composition A, & p <0.05, && p < 0.01, &&& p < 0.001.

[0049] Figure 4Typical images of triglyceride staining intensity in the blood vessels of zebrafish tails in each experimental group of Example 9.

[0050] Note: Figure 4 The example image in the diagram illustrates the analysis site, and the analysis area (dashed line) refers to the blood vessels in the zebrafish tail.

[0051] Figure 5 This is an evaluation of the lipid-lowering efficacy of composition A in Example 10.

[0052] Note: Compared with the model control group, * p < 0.05, ** p < 0.01, *** p < 0.001.

[0053] Figure 6 This is an evaluation of the lipid-lowering efficacy of composition A in Example 11.

[0054] Note: Compared with the model control group, * p < 0.05, ** p < 0.01, *** p < 0.001. Detailed Implementation

[0055] The following are specific embodiments of the present invention, which further describe the technical solution of the present invention. However, the scope of protection of the present invention is not limited to these embodiments. It should be noted that for those skilled in the art, any changes or equivalent substitutions that do not depart from the concept of the present invention are included within the scope of protection of the present invention.

[0056] The sources of the solvents, equipment, test kits, etc. involved in the embodiments of this invention are as follows: Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); Precision electronic balance (CP214, OHAUS, USA); Motorized focusing continuous zoom fluorescence microscope (AZ100, Nikon, Japan); Microinjection apparatus (IM300, Narishige, Japan); Needle puller (PC-10, Narishige, Japan); 6-well plate (Zhejiang Beilanbo Biotechnology Co., Ltd., China).

[0057] Atorvastatin calcium tablets (hereinafter referred to as atorvastatin calcium), commercially available positive control drug, Pfizer Pharmaceuticals Co., Ltd., white tablets, solvent is DMSO.

[0058] Egg yolk powder (batch number 20230203, Zhejiang Agribusiness Biotechnology Co., Ltd., China); Oil Red O (lot number SHBN4926, Sigma, USA); BCA protein concentration assay kit (batch number 19H13B89, BOSTER, China). Low-density lipoprotein cholesterol (LDL-C) kit (batch number 20240104, Nanjing Jiancheng Biotechnology Institute, China); High-density lipoprotein cholesterol (HDL-C) kit (batch number 20241015, Nanjing Jiancheng Biotechnology Institute, China).

[0059] Example 1, hypolipidemic composition A The raw material formula of lipid-lowering composition A is as follows: soybean peptide 0.5g, bitter melon peptide 0.5g, natto freeze-dried powder 0.03g, black pepper extract 0.01g, bamboo leaf flavonoids 0.12g, total 1.16g.

[0060] Preparation of raw materials for lipid-lowering composition A: Weigh out soybean peptide, bitter melon peptide, natto freeze-dried powder, black pepper extract, and bamboo leaf flavonoids according to the formula amount, mix them well, and grind them into powder to obtain the product.

[0061] Furthermore, the aforementioned raw material of composition A is mixed evenly with a basic energy substrate (whey protein concentrate for proteins, inulin for dietary fiber, and fish oil powder for fatty acids and / or lipids) in a certain proportion to obtain lipid-lowering composition A. Composition A can be formulated into suitable dosage forms according to actual market applications, including but not limited to: powder, tablets, granules, capsules, solutions, etc.

[0062] It should be noted that this invention aims to investigate the efficacy effects of different dosages of raw materials in the lipid-lowering composition. Therefore, the components used as basic energy substrates can be added with reference to the recommended amounts of protein, dietary fiber, fatty acids, and / or lipids specified in the "Chinese Dietary Guidelines (2022)". The specific types of each component can also be arbitrarily selected according to the following scheme: For example, proteins can be selected from one or more of whey protein concentrate, soy protein isolate, yeast protein, pea protein, casein, and lactoferrin; Dietary fiber is selected from one or more of the following: pectin cellulose, L-arabinose, chitosan, yeast β-glucan, fucoidan, galactooligosaccharide, galactomannan, fructooligosaccharide, xylooligosaccharide, inulin, polydextrose, isomaltulose, resistant dextrin, stachyose, and psyllium husk powder. Fatty acids and / or may be selected from one or more of DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), diglycerides, medium-chain triglycerides, medium- and long-chain triglycerides, palm kernel oil, egg yolk lecithin, soybean lecithin, olive oil powder, sunflower seed oil powder, and fish oil powder.

[0063] Example 2, hypolipidemic composition B The basic energy substrate contained in the lipid-lowering composition B is added in the same manner as in Example 1.

[0064] The raw material formula of lipid-lowering composition B is as follows: 2.5g soybean peptide, 1.5g bitter melon peptide, 0.12g natto freeze-dried powder, 0.04g black pepper extract, and 0.48g bamboo leaf flavonoids, totaling 4.64g. Preparation of raw materials for lipid-lowering composition B: Weigh out the soybean peptide, bitter melon peptide, natto freeze-dried powder, black pepper extract, and bamboo leaf flavonoids according to the formula amounts, mix well, and grind into powder.

[0065] Example 3, hypolipidemic composition C The basic energy substrate contained in the lipid-lowering composition C is added in the same manner as in Example 1.

[0066] The formula of ingredients contained in lipid-lowering composition C is as follows: 2.5g soybean peptide, 0.5g bitter melon peptide, 0.09g natto freeze-dried powder, 0.03g black pepper extract, 0.36g bamboo leaf flavonoids, totaling 3.48g.

[0067] Preparation of raw materials for lipid-lowering composition C: Weigh out soybean peptides, bitter melon peptides, natto freeze-dried powder, black pepper extract, and bamboo leaf flavonoids according to the formula amount, mix them well, and grind them into powder to obtain the product. Example 4, hypolipidemic composition D The basic energy substrate contained in the lipid-lowering composition D is added in the same manner as in Example 1.

[0068] The raw material formula of lipid-lowering composition D is as follows: 0.5g soybean peptide, 1.5g bitter melon peptide, 0.06g natto freeze-dried powder, 0.02g black pepper extract, and 0.24g bamboo leaf flavonoids, totaling 2.32g. Preparation of raw materials for lipid-lowering composition D: Weigh out the soybean peptide, bitter melon peptide, natto freeze-dried powder, black pepper extract, and bamboo leaf flavonoids according to the formula amounts, mix well, and grind into powder.

[0069] Example 5, hypolipidemic composition E The basic energy substrate contained in the lipid-lowering composition E is added in the same manner as in Example 1.

[0070] The raw material formula contained in lipid-lowering composition E is as follows: 0.5g soybean peptide, 0.5g bitter melon peptide, 0.03g natto freeze-dried powder, 0.04g black pepper extract, 0.12g bamboo leaf flavonoids, totaling 1.19g.

[0071] Preparation of raw materials for lipid-lowering composition E: Weigh out soybean peptides, bitter melon peptides, natto freeze-dried powder, black pepper extract, and bamboo leaf flavonoids according to the formula amount, mix them well, and grind them into powder to obtain the product.

[0072] Example 6, hypolipidemic composition F The basic energy substrate contained in the lipid-lowering composition F is added in the same manner as in Example 1.

[0073] The raw material formula contained in the lipid-lowering composition F is as follows: 0.5g soybean peptide, 0.5g bitter melon peptide, 0.03g natto freeze-dried powder, 0.01g chili extract, 0.12g bamboo leaf flavonoids, totaling 1.16g.

[0074] Preparation of raw materials for lipid-lowering composition E: Weigh out soybean peptide, bitter melon peptide, natto freeze-dried powder, chili extract, and bamboo leaf flavonoids according to the formula amount, mix them well, and grind them into powder to obtain the product.

[0075] Example 7, hypolipidemic composition G The basic energy substrate contained in the lipid-lowering composition G is added in the same manner as in Example 1.

[0076] The raw material formula contained in the lipid-lowering composition G is as follows: 0.5g soybean peptide, 0.5g bitter melon peptide, 0.03g natto freeze-dried powder, 0.12g bamboo leaf flavonoids, totaling 1.15g.

[0077] Preparation of raw materials for lipid-lowering composition G: Weigh soybean peptide, bitter melon peptide, natto freeze-dried powder, and bamboo leaf flavonoids according to the formula amount, mix them well, and grind them into powder to obtain the product.

[0078] Example 8, influence of mass ratio of soybean peptides and Momordica charantia peptides on hypolipidemic efficacy In this example, it is assumed that the types of each component in the raw material formula of the lipid-lowering composition remain unchanged, the total amount of complex peptides is a fixed value (i.e., the sum of the masses of soybean peptides and bitter melon peptides is fixed), and the mass ratio of complex peptides to black pepper extract is a fixed value (e.g., 100:1). By examining the difference in the mass ratio of soybean peptides to bitter melon peptides, the difference in the lipid-lowering efficacy of the resulting composition is explored.

[0079] In this example, the mass ratio of soybean peptide to bitter melon peptide was screened and investigated, set to 1:3, 1:1, 5:3, and 5:1, forming compositions A to D (see Table 1). The raw material formulations of compositions A to D are as described in Examples 1 to 4.

[0080] In this embodiment, the raw material preparation method of compositions A to D is the same as that in Example 1; the basic energy substrate contained in compositions A to D is added in the same way as in Example 1.

[0081] Experimental Methods: Zebrafish of the Albino strain with a 5-day-of-flight (dpf) melanin allele mutation were randomly selected and placed in beakers. Each beaker (experimental group) contained 15 zebrafish. The raw materials of compositions A, B, C, and D provided by this invention, as well as the positive control drug atorvastatin calcium, were administered in water. A normal control group and a model control group were also established, with each group containing 25 mL. Except for the normal control group, all experimental groups were given a high-fat diet in water to establish a zebrafish hyperlipidemia model.

[0082] After treatment at 28℃ for 48 h, samples were collected, stained with oil red rubicle, and 8 zebrafish were randomly selected from each experimental group and photographed under a dissecting microscope. Data were analyzed and collected using NIS-ElementsD3.20 advanced image processing software. The intensity of triglyceride staining in the blood vessels of zebrafish tails was analyzed and statistically analyzed. The lipid-lowering efficacy of the samples was evaluated based on the statistical analysis results of this index.

[0083] Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software, and p < 0.05 was considered statistically significant.

[0084] The experimental results are shown in Table 1. Figure 1 and Figure 2 .

[0085] Table 1. Evaluation of lipid-lowering efficacy in each experimental group (n=8) .

[0086] Note: Compared with the model control group, * p < 0.05, ** p < 0.01, *** p < 0.001; compared with the positive control group, # p < 0.05, ## p < 0.01, ### p < 0.001.

[0087] From Table 1, Figure 1 and Figure 2 From this, we can know that 1) There were significant differences between the normal control group and the model control group. p< 0.001), and there was also a significant difference between the positive control group and the model control group ( p < 0.001) indicates successful modeling; 2) Compared with the model control group, compositions A, B, C, and D provided by this invention can significantly reduce the staining intensity of triglycerides in the blood vessels of zebrafish tails. p < 0.001), indicating that compositions A, B, C, and D all have a significant effect in reducing triglyceride levels and can achieve the effect of lowering blood lipids; 3) Compared with the positive control group, the staining intensity of triglycerides in the zebrafish tail blood vessels in composition D was significantly higher than that in the positive control group. p < 0.001), although the staining intensity of triglycerides in the zebrafish tail blood vessels in composition C was lower than that in the positive control group, there was no significant difference. p > 0.05), the staining intensity of triglycerides in the zebrafish tail blood vessels in compositions A and B was significantly lower than that in the positive control group ( p < 0.01, p < 0.001); indicating that the lipid-lowering effect of composition D is significantly inferior to that of the positive control drug, the lipid-lowering effect of composition C is comparable to that of the positive control drug, and the lipid-lowering effects of compositions A and B are significantly superior to those of the positive control drug, especially composition A.

[0088] Therefore, in the composition provided by the present invention, the mass ratio of soybean peptide to bitter melon peptide is selected as (1:1) to (5:3), and the optimal mass ratio is 1:1.

[0089] Example 9, influence of type and amount of plant extract on hypolipidemic efficacy This embodiment aims to investigate the effects of specific plant extract types and specific dosage ratios of compound peptides and plant extracts on lipid-lowering efficacy, especially the difference in lipid-lowering efficacy between the composition formed in this invention and statin-type lipid-lowering drugs (such as atorvastatin calcium).

[0090] To achieve the research objectives, the following investigation scheme was designed with reference to Example 1.

[0091] 1. Assuming that the amount of each component in the composition provided by the present invention remains constant, and only the type of plant extract is changed, the lipid-lowering effect of the resulting composition is investigated. The plant extracts were categorized as follows: black pepper extract (composition A), chili pepper extract (composition F), and no plant extracts (composition G).

[0092] 2. Assuming that the types of each component in the composition provided by the present invention remain unchanged, only the ratio of the amount of compound peptide (i.e., soybean peptide + bitter melon peptide) to plant extract is changed, and the lipid-lowering effect of the resulting composition is examined. The ratio of compound peptides to plant extracts was set as follows: 100:1 (compositions A and B), 25:1 (composition E).

[0093] Experimental Methods: Five dpf (day-to-flight) zebrafish of the Albino strain with a melanin allele mutation were randomly selected and placed in beakers. Each beaker (experimental group) contained 15 zebrafish. Samples were administered in water. The following experimental groups were established: normal control group, model control group, positive control drug atorvastatin calcium, raw material of composition A, raw material of composition B, raw material of composition E, raw material of composition F, atorvastatin calcium + raw material of composition A, atorvastatin calcium + raw material of composition B, atorvastatin calcium + raw material of composition E, and atorvastatin calcium + raw material of composition F. Each group had a volume of 25 mL. Except for the normal control group, all experimental groups were given a high-fat diet in water to establish a zebrafish hyperlipidemia model.

[0094] After treatment at 28℃ for 48 h, samples were collected, stained with oil red rubicle, and 8 zebrafish were randomly selected from each experimental group and photographed under a dissecting microscope. Data were analyzed and collected using NIS-ElementsD3.20 advanced image processing software. The intensity of triglyceride staining in the blood vessels of zebrafish tails was analyzed and statistically analyzed. The lipid-lowering efficacy of the samples was evaluated based on the statistical analysis results of this index.

[0095] Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software, and p < 0.05 was considered statistically significant.

[0096] The experimental results are shown in Table 2. Figure 3 and Figure 4 .

[0097] Table 2. Evaluation of lipid-lowering efficacy in each experimental group (n=8) .

[0098] Note: Compared with the model control group, * p < 0.05, ** p < 0.01, *** p < 0.001; Compared with the positive control group, # p < 0.05, ## p < 0.01, ### p < 0.001; Compared with composition E, ☆ p < 0.05, ☆☆ p < 0.01, ☆☆☆ p < 0.001; Compared with composition B, △ p < 0.05, △△p < 0.01, △△△ p < 0.001; Compared with composition A, & p < 0.05, && p < 0.01, &&& p < 0.001.

[0099] From Table 2, Figure 3 and Figure 4 From this, we can know that 1) There were significant differences between the normal control group and the model control group. p < 0.001), and there was also a significant difference between the positive control group and the model control group ( p < 0.001) indicates successful modeling; 2) Compared with the model control group, the staining intensity of triglycerides in the zebrafish tail blood vessels in composition F was reduced, but the difference was not significant. p > 0.05), Composition G, Composition A, Composition B, Composition E, Composition A + positive control, Composition B + positive control, and Composition E + positive control all significantly reduced the staining intensity of triglycerides in the blood vessels of zebrafish tails. p < 0.05, p < 0.001), indicating that except for composition F, the other experimental groups all had a significant effect of reducing triglyceride levels and could play a role in lowering blood lipids; 3) Compared with the positive control group, the staining intensity of triglycerides in the zebrafish tail blood vessels of compositions F and G was higher than that of the positive drug atorvastatin calcium, indicating that the lipid-lowering effect of compositions F and G was inferior to that of the positive drug; similarly, although the staining intensity of triglycerides in the zebrafish tail blood vessels of composition E + positive drug and composition E was slightly lower than that of the positive drug, there was no significant difference, indicating that the lipid-lowering effect of composition E was comparable to that of the positive drug, and the combination of composition E and statin positive drugs failed to achieve synergistic lipid-lowering effect; 4) The staining intensity of triglycerides in the zebrafish tail vessels of both composition B and composition B was significantly lower than that of the positive drug atorvastatin calcium. p < 0.001), but there was no significant difference in the staining intensity of triglycerides in the blood vessels of zebrafish between "Composition B + Positive Agent" and Composition B alone ( p > 0.05); This indicates that the lipid-lowering effect of composition B is significantly better than that of the positive control drug. However, when composition B is used in combination with a statin positive control drug, the lipid-lowering effect is better than that of the positive control drug alone, which is equivalent to the use of composition B alone. Therefore, it cannot fully play a synergistic role in lowering lipids. 5) Composition A + positive control drug: The staining intensity of triglycerides in the zebrafish tail blood vessels of Composition A was significantly lower than that of the positive control drug atorvastatin calcium (…). p< 0.001), and compared with Composition A alone and positive drug alone, the staining intensity of triglycerides in the blood vessels of zebrafish tails was significantly different (Composition A + positive drug). p < 0.001); indicating that the lipid-lowering effect of composition A is significantly better than that of the positive control drug, and that when composition A is used in combination with statin positive control drugs, the lipid-lowering effect is better than that of using the positive control drug alone or composition A alone, thus it can fully play a synergistic role in lowering blood lipids.

[0100] In summary, the amount and dosage of black pepper extract can affect the synergistic lipid-lowering effect when used in combination with statins (such as atorvastatin calcium). In the compositions provided by this invention, when the mass ratio of the complex peptide to the black pepper extract is 100:1, and the mass ratio of soybean peptide to bitter melon peptide in the complex peptide is (1:1) to (5:3), the lipid-lowering efficacy of this composition is significantly better than that of atorvastatin calcium, for example, composition A in Example 1 and composition B in Example 2. Furthermore, only composition A, when used in combination with atorvastatin calcium, can achieve a synergistic lipid-lowering effect.

[0101] Example 10, evaluation of other hypolipidemic efficacy indicators of hypolipidemic composition A (low-density lipoprotein cholesterol) This embodiment aims to evaluate the lipid-lowering effect by assessing changes in low-density lipoprotein cholesterol levels in a zebrafish model.

[0102] Experimental Methods: Wild-type AB strain zebrafish, 5 days post-fertilization (dpf), were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker (experimental group). The raw material of Composition A provided by this invention was administered in water. A normal control group and a model control group were also set up, with each group having a volume of 25 mL. Three biological replicates were performed. Except for the normal control group, each experimental group was given a high-fat diet in water to establish a zebrafish hyperlipidemia model.

[0103] After treatment at 28℃ for 48 h, zebrafish samples from each experimental group were collected. Data were acquired using a multi-functional microplate reader (MEMB) according to the kit instructions, and the low-density lipoprotein cholesterol (LDL-C) content in the zebrafish was analyzed. The lipid-lowering efficacy of the samples was evaluated based on the statistical analysis results of this index. Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software; p < 0.05 indicated statistical significance.

[0104] The experimental results are shown in Table 3 and Figure 5 .

[0105] Table 3. Evaluation of lipid-lowering efficacy (low-density lipoprotein cholesterol) in each experimental group (n=3) .

[0106] Note: Compared with the model control group, * p < 0.05,** p < 0.01, *** p < 0.001.

[0107] From Table 3 and Figure 5 As can be seen from the data, compared with the model control group, the composition A provided by the present invention can significantly reduce the content of low-density lipoprotein cholesterol (LDL cholesterol). p < 0.05), indicating that composition A has lipid-lowering effects.

[0108] Example 11, evaluation of other hypolipidemic efficacy indicators of hypolipidemic composition A (high-density lipoprotein cholesterol) This embodiment aims to evaluate the lipid-lowering effect by assessing changes in high-density lipoprotein cholesterol levels in a zebrafish model.

[0109] Experimental Methods: Wild-type AB strain zebrafish, 5 days post-fertilization (dpf), were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker (experimental group). The raw material of Composition A provided by this invention was administered in water. A normal control group and a model control group were also set up, with each group having a volume of 25 mL. Three biological replicates were performed. Except for the normal control group, each experimental group was given a high-fat diet in water to establish a zebrafish hyperlipidemia model.

[0110] After treatment at 28℃ for 48 h, zebrafish samples were collected from each experimental group. Data were acquired using a multi-functional microplate reader (MEMB) according to the kit instructions, and the high-density lipoprotein cholesterol (HDL-C) content in the zebrafish was analyzed. The lipid-lowering efficacy of the samples was evaluated based on the statistical analysis results of this index. Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software; p < 0.05 indicated statistical significance.

[0111] The experimental results are shown in Table 4 and Figure 6 .

[0112] Table 4. Evaluation of lipid-lowering efficacy (high-density lipoprotein cholesterol) in each experimental group (n=3) .

[0113] Note: Compared with the model control group, * p < 0.05, ** p < 0.01, *** p < 0.001.

[0114] From Table 4 and Figure 6 As can be seen from the data, compared with the model control group, the composition A provided by the present invention can significantly increase the content of high-density lipoprotein cholesterol (HDL-C). p < 0.05), indicating that composition A has lipid-lowering effects.

Claims

1. A hypolipidemic composition comprising a supramolecular group complex peptide, consisting of a raw material and a basic energy substrate, wherein the basic energy substrate comprises a protein, a dietary fiber, a fatty acid and / or a lipid; characterized in that, The raw materials include a complex peptide, a freeze-dried powder of natto, a black pepper extract, and bamboo leaf flavones, and the complex peptide is composed of soybean peptides and momordica charantia peptides, and the mass ratio of the soybean peptides to the momordica charantia peptides is (1:1) to (5:3).

2. The hypolipidemic composition according to claim 1, wherein The mass ratio of the soybean peptides to the momordica charantia peptides in the complex peptide is 1:1 or 5:

3.

3. The hypolipidemic composition according to claim 1, wherein The mass ratio of the complex peptide to the black pepper extract is (25:1) to (100:1).

4. The hypolipidemic composition according to claim 3, wherein The mass ratio of the complex peptide to the black pepper extract is 100:

1.

5. The hypolipidemic composition according to any one of claims 1 to 4, wherein, The raw materials include the following components in the following amounts: 0.5 to 2.5 parts by mass of soybean peptides, 0.5 to 1.5 parts by mass of momordica charantia peptides, 0.03 to 0.25 parts by mass of a freeze-dried powder of natto, 0.01 to 0.04 parts by mass of a black pepper extract, and 0.12 to 0.5 parts by mass of bamboo leaf flavones.

6. The hypolipidemic composition according to claim 5, wherein The raw materials include the following components in the following amounts: 0.5 parts by mass of soybean peptides, 0.5 parts by mass of momordica charantia peptides, 0.03 parts by mass of a freeze-dried powder of natto, 0.01 parts by mass of a black pepper extract, and 0.12 parts by mass of bamboo leaf flavones.

7. The hypolipidemic composition according to claim 5, wherein The raw materials include the following components in the following amounts: 2.5 parts by mass of soybean peptides, 1.5 parts by mass of momordica charantia peptides, 0.12 parts by mass of a freeze-dried powder of natto, 0.04 parts by mass of a black pepper extract, and 0.48 parts by mass of bamboo leaf flavones.

8. The hypolipidemic composition according to any one of claims 1 to 7, wherein, In the basic energy substrate: The protein is selected from one or more of the following: concentrated whey protein, soybean protein isolate, yeast protein, pea protein, casein protein, lactoferrin; The dietary fiber is selected from one or more of the following: pectin cellulose, L-arabinose, chitosan, yeast beta-glucan, fucoidan, galactooligosaccharide, galactomannan, fructooligosaccharide, xylooligosaccharide, inulin, polydextrose, isomaltulose, resistant dextrin, stachyose, psyllium husk powder; The fatty acid and / or lipid is selected from one or more of the following: DHA, EPA, diglyceride, medium-chain triglyceride, medium-long-chain triglyceride, palm kernel oil, egg yolk phospholipid, soybean phospholipid, fish oil powder, olive oil powder, sunflower seed oil powder, and fish oil powder.

9. Use of the hypolipidemic composition according to any one of claims 1 to 8 in the preparation of a drug or functional food for preventing or improving hyperlipidemia.

10. Use according to claim 9, characterized in that, The drug or functional food comprises the hypolipidemic composition according to any one of claims 1 to 8 and a pharmaceutically acceptable carrier.

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