Composition with auxiliary blood lipid lowering effect and application thereof

Abstract

The present invention belongs to the fields of biomedicine and food technology, and specifically relates to the use of a composition in the preparation of a drug or health food having the effect of assisting in lowering blood lipids. The composition comprises a water-soluble tomato concentrate, Nannochloropsis algae oil, and / or fish oil. Through experimental research, the present invention unexpectedly discovered that the water-soluble tomato concentrate and Nannochloropsis algae oil and / or fish oil have a synergistic effect in assisting in lowering blood lipids. Combining the two can significantly reduce levels of triglycerides and cholesterol, particularly low-density lipoprotein (LDL), achieving excellent lipid-lowering efficacy.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine and food technology, and in particular to a composition with auxiliary blood lipid lowering effect and its application. Background Art

[0002] Dyslipidemia is a major risk factor for cardiovascular disease, primarily manifested by elevated triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), or total cholesterol (TC). Long-term high blood lipids can accelerate the development of atherosclerosis and increase the risk of serious complications such as coronary heart disease, stroke, fatty liver disease, acute pancreatitis, and diabetes. Furthermore, high blood lipids can lead to high blood pressure, compromise bone health, increase the risk of osteoporosis, and even impair cognitive function.

[0003] EPA (eicosapentaenoic acid), a type of omega-3 fatty acid, is widely recognized for its lipid-lowering effects. Existing studies have shown that high-purity EPA preparations can significantly lower triglyceride (TG) levels, thereby reducing the risk of cardiovascular disease. Krill oil and fish oil supplements are rich in omega-3 fatty acids. They contain EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), which can significantly lower blood triglyceride levels, raising the omega-3 index while maintaining low-density lipoprotein cholesterol (LDL-C) levels. However, the use of krill oil as an auxiliary lipid-lowering agent carries risks. It may increase the risk of bleeding in people taking anticoagulants and may cause side effects such as flatulence, bloating, or diarrhea. Long-term high-dose fish oil use may also increase bleeding tendencies and reduce immune system activity. It may not be suitable for patients with liver disease, those allergic to fish or seafood, diabetics, or those with hypertension. In addition, the Omega-3 fatty acids in fish oil are easily oxidized during storage, producing saturated fatty acids, which may lead to increased blood lipids. In addition, EPA and DHA in fish oil are difficult to completely separate, and fish oil resources are gradually depleted due to marine pollution and overfishing.

[0004] In the MARINE and ANCHOR studies, subjects took 2g or 4g of 97% ethyl ester EPA (EE-EPA) daily, and after 12 weeks, the triglyceride (TG) content in the blood and red blood cells was significantly reduced, and the amount of TG reduction was dose-dependent with the amount of EPA taken. In these studies, there was no significant decrease in low-density lipoprotein cholesterol (LDL). In the REDUCE-IT (Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapentethyl for hypertriglyceridemia [J]. NEngl J Med, 2019, 380(1): 11-22.) study, it was found that the intake of omega-3 fatty acids would lead to the risk of atrial fibrillation, and the dose-dependent effect was observed. The higher the dose, the higher the risk. The European Medicines Agency issued a warning: EPA or DHA intake of more than 2g will increase the risk of atrial fibrillation. According to a meta-analysis, the risk increased by 11% for every 1g / day increase.

[0005] Nannochloropsis gaditana, also known as microchloropsis or microgreen algae, is a widely distributed marine algae that only synthesizes EPA but not DHA. The cells accumulate large amounts of EPA and other Omega-3 polyunsaturated fatty acids, which have special health benefits and extremely high bioavailability. It is considered to be a potential alternative to fish oil and provides an excellent raw material for the preparation of pure EPA products. Nannochloropsis gaditana was approved as a new food ingredient in China in 2021, and its extract, Nannochloropsis gaditana oil, was approved as a new food ingredient in China in 2024. Nannochloropsis oil has high nutritional and medicinal value and high biosafety. It has no obvious toxic side effects when consumed for a long time and has great application potential in the fields of nutritional supplements and functional foods. At the same time, Nannochloropsis is a microalgae that can be artificially cultivated. Obtaining Nannochloropsis oil through artificial cultivation and extraction is more sustainable than extracting fish oil from deep-sea fish and is not affected by fluctuations in fishery resources.

[0006] Currently, the results of two human efficacy trials of Nannochloropsis extract have been published. One of them is a randomized double-blind controlled trial of 120 people (Rao A, Briskey D, Nalley JO, et al. Omega-3 Eicosapentaenoic Acid (EPA) Rich Extract from the Microalga Nannochloropsis Decreases Cholesterol in Healthy Individuals: A Double-Blind, Randomized, Placebo-Controlled, Three-Month Supplementation Study [J]. Nutrients, 2020, 12 (6).). The results showed that taking 1g of Nannochloropsis extract per day significantly increased the Omega-3 index and plasma EPA concentration, reduced very low-density lipoprotein cholesterol (VLDL) by 25%, and significantly reduced total cholesterol levels (TC). Another real-world post-market cohort study (Ganuza E, EtomiEH, Olson M, Whisner CM. Omega-3eicosapentaenoic polar-lipid rich extract frommicroalgae Nannochloropsis decreases plasma triglycerides and cholesterol ina real-world normolipidemic supplement consumer population. FrontNutr. 2024Feb6; 11: 1293909.) showed that taking 1000-1100 mg of Nannochloropsis extract daily experienced a significant and sustained decrease in triglycerides (TG) in the third and sixth months. In addition, after 6 months of supplementation, TC and non-high-density lipoprotein cholesterol (Non-HDL-C) decreased by 5.0% and 5.5%, respectively. However, both of the above experiments require a daily intake of 1g or more of Nannochloropsis extract to achieve the effect of significantly lowering blood cholesterol (TC). That is, in the two human studies on the above-mentioned Nannochloropsis algae extracts, some blood lipid indicators were reduced when the intake was above 1g / d, but the LDL level did not decrease significantly.

[0007] Water-soluble tomato concentrate is a product approved by the European Food Safety Authority for maintaining normal platelet aggregation and has received GRAS certification from the US FDA. Multiple test results have confirmed that water-soluble tomato concentrate contains naturally occurring antiplatelet compounds that, when ingested, can inhibit platelet activity in healthy individuals and reduce platelet aggregation, thereby maintaining blood in a fluid and hypocoagulable state. This prevents the formation of microaggregates in the circulatory system and platelet adhesion to blood vessel walls or fatty plaques, thereby maintaining healthy blood circulation. Currently, water-soluble tomato concentrate has been used in Europe as a nutritional supplement and as a It is sold under the brand name. There are already literatures showing that (Wang Yufang, He Ruikun, Zhang Xuguang. Study on the antioxidant and lipid-lowering effects of water-soluble tomato concentrate [J]. Journal of Food Safety and Quality, 2020, 11(13): 5.) water-soluble tomato concentrate significantly reduces serum TC levels in a high-fat diet-induced hyperlipidemia rat model, but the test results for TG and LDL-C are not significant. Summary of the Invention

[0008] As mentioned above, the existing technologies have the following problems: (1) Only high doses of krill oil and fish oil supplements can significantly lower blood lipids, but high doses of omega-3 fatty acid preparations may increase the risk of cardiovascular and cerebrovascular diseases; (2) It is still necessary to take more than 1g of Nannochloropsis algae extract daily to achieve the effect of lowering TC levels, and it is not possible to lower LDL; (3) Products that can simultaneously lower TG / TC and LDL in blood lipids are very limited. Therefore, it is urgent to provide a blood lipid-lowering preparation that can significantly lower multiple blood lipid indicators or improve various types of hyperlipidemia with a lower dose. Based on the above problems, the present invention provides a composition that can achieve auxiliary blood lipid-lowering effects with a low dose intake, and the use of the composition in the preparation of a drug or health food with auxiliary blood lipid-lowering effects.

[0009] The specific technical solutions are as follows:

[0010] In a first aspect, the present invention provides a composition for use in preparing a product for assisting in lowering low-density lipoprotein levels. The composition consists of a water-soluble tomato concentrate and Nannochloropsis spp. oil.

[0011] In one embodiment, the mass ratio of the water-soluble tomato concentrate to the Nannochloropsis oil is 1-6:15-30.

[0012] In some embodiments, the mass ratio of the water-soluble tomato concentrate to Nannochloropsis oil is 1:15, 1:20, 1.5:20, 1:25, 1:30, 2:15, 2:20, 2:25, 3:15, 3:20, 3:25, 4:15, 4:20, 4:25, 5:15, 5:20, 5:30, 6:15, 6:20, 6:25.

[0013] In one embodiment, the mass ratio of the water-soluble tomato concentrate to the Nannochloropsis oil is 1.5-3:20.

[0014] In a second aspect, the present invention provides a composition having the effect of assisting in lowering blood lipids, wherein the composition is composed of a water-soluble tomato concentrate and Nannochloropsis spp. oil.

[0015] In one embodiment, the mass ratio of the water-soluble tomato concentrate to the Nannochloropsis oil is 1-6:15-30; preferably, the mass ratio of the water-soluble tomato concentrate to the Nannochloropsis oil is 1.5-3:20.

[0016] In the present invention, the auxiliary blood lipid lowering effect is to assist in lowering one or more of the levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) in the blood. Preferably, the auxiliary blood lipid lowering effect is to assist in lowering the levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) in the blood.

[0017] In a third aspect, the present invention provides a use of a composition in preparing a product having an auxiliary lipid-lowering effect, wherein the composition consists of a water-soluble tomato concentrate and fish oil.

[0018] In one embodiment, the mass ratio of the water-soluble tomato concentrate to the fish oil is 1-6:20-40.

[0019] In some embodiments, the mass ratio of the water-soluble tomato concentrate to fish oil is 1:20, 1:25, 1:30, 1:40, 2:20, 2:25, 3:20, 3:25, 3:32, 3:40, 4:20, 4:25, 4:32, 5:20, 5:25, 5:32, 6:20, 6:25, 6:32, or 6:40.

[0020] In one embodiment, the mass ratio of the water-soluble tomato concentrate to the fish oil is 3 to 5:32.

[0021] In one embodiment, the auxiliary blood lipid-lowering effect is to reduce one or more levels of TC, TG and LDL in the blood; preferably, the auxiliary blood lipid-lowering effect is to reduce TC, TG and LDL in the blood.

[0022] In a fourth aspect, the present invention provides a composition having the effect of assisting in lowering blood lipids, comprising a water-soluble tomato concentrate and fish oil.

[0023] In one embodiment, the mass ratio of the water-soluble tomato concentrate to the fish oil is 1-6:20-40; preferably, the mass ratio of the water-soluble tomato concentrate to the fish oil is 3-5:32.

[0024] In the present invention, the products include food, medicine, and health food; that is, the composition of the present invention can be added to food, medicine, and health food as the main functional ingredient therein to play a role; preferably, the product of the present invention is a health food.

[0025] In some examples, the products of the present invention may further include excipients permitted for use in pharmaceuticals, general foods, health foods, and special medical foods. For example, the products may further include diluents, thickeners, antioxidants, pigments, disintegrants, lubricants, and buffers.

[0026] In some examples, in the present invention, the product may further include other functional substances, which may include vitamins, minerals, and animal and plant extracts.

[0027] In some examples, the water-soluble tomato concentrate of the present invention is combined with Nannochloropsis oil and fish oil to form a composition for aiding in lowering blood lipids. Because Nannochloropsis oil contains no or essentially no DHA, its addition allows for convenient adjustment of the ratio of EPA to DHA in the composition. Furthermore, the plant oil components of Nannochloropsis oil and the animal oil components of fish oil complement each other, further enhancing nutritional benefits.

[0028] In one embodiment, the present invention provides a product for assisting in lowering blood lipids, comprising water-soluble tomato concentrate, Nannochloropsis spp., and fish oil.

[0029] In some examples, the dosage form of the product of the present invention is a product form or dosage form conventionally used in food, medicine, and health food; for example, food can be made into biscuits, candies, cakes, beverages, jellies, and chocolates; as a medicine or health food, it can be made into tablets, soft capsules, hard capsules, powders, oral liquid preparations, gels, and pills.

[0030] Currently, water-soluble tomato concentrates are regulated as common foods in Europe, the United States, and China. Water-soluble tomato concentrates (WSTC) are primarily composed of heat-stable, water-soluble compounds derived from tomatoes, which serve as their primary bioactive ingredients. The primary bioactive ingredients in WSTC may originate from the pulp of tomato fruits and / or the juice surrounding tomato seeds. Solids, fat-soluble components, and water-soluble sugars from these sources are then removed, followed by concentration and drying to produce the WSTC. Specifically, the WSTC is obtained by separating the water-soluble components from tomatoes primarily through physical methods (centrifugation, filtration, etc.), followed by concentration and desugaring. It is understood that lycopene is a fat-soluble component; therefore, the WSTC of the present invention contains no or substantially no lycopene.

[0031] It should be understood by those skilled in the art that the water-soluble tomato concentrate of the present invention can be purchased from Provis Natural Products Co., Ltd. or its authorized sales agency. In addition, patents WO 99 / 55350, WO 2010 / 049707 and CN102271697 also disclose methods for producing water-soluble tomato concentrates that can be used in the present invention. Therefore, the water-soluble tomato concentrate used in the present invention can also be prepared according to WO 99 / 55350, WO 2010 / 049707 or CN102271697. If prepared according to the methods described in WO 99 / 55350, WO 2010 / 049707 or CN102271697, it should be ensured that the ingredients of the prepared water-soluble tomato concentrate meet the above requirements. In one embodiment, according to the method of CN102271697, Figure 2 and Figure 4 The process described is a preferred method for producing a water-soluble tomato concentrate.

[0032] In one embodiment, the water-soluble tomato concentrate used in the present invention can be prepared using the method described in CN102271697, which comprises:

[0033] (a) preparing an initial mixture of tomato homogenate;

[0034] (b) separating the water-soluble component from the initial mixture, wherein the separation temperature is not higher than 60°C;

[0035] (c) filtering and concentrating the water-soluble component, wherein the concentration temperature is not higher than 60°C.

[0036] Preferably, the temperature of the initial mixture in step (a) is not higher than 35°C.

[0037] Preferably, the pH of the initial mixture in step (a) does not exceed 5.5.

[0038] Preferably, the browning index of the initial mixture does not exceed 0.4 AU at 4% solids, wherein the browning index is defined as the absorbance of the soluble fraction at 420 nm.

[0039] Preferably, in step (b), water-insoluble solids with a particle size greater than 500 μm are separated and removed from mixture A to obtain a water-soluble component.

[0040] Preferably, the separation in step (b) comprises at least one of centrifugal separation and natural sedimentation separation, and the water-soluble component is the supernatant obtained after separation.

[0041] Preferably, in step (c), the filtration is performed using a filter membrane. Without limitation, the pore size of the filter membrane used for filtration is no greater than 1 μm, specifically 0.2 μm.

[0042] Preferably, the concentration in step (c) can be carried out by membrane filtration concentration, low-temperature evaporation concentration, freeze-drying concentration or spray drying concentration.

[0043] Preferably, in the step (c), the step of removing free sugars from the water-soluble components before filtering is further included.

[0044] Beneficial effects

[0045] The present invention accidentally discovered through experimental research that water-soluble tomato concentrate and Nannochloropsis oil and / or fish oil have a synergistic effect in assisting in lowering blood lipids. The combination of the two can significantly reduce the levels of triglycerides, cholesterol and low-density lipoprotein, achieving excellent auxiliary blood lipid-lowering effects.

[0046] The composition of the present invention has a low daily dosage, thus avoiding the safety risks that may be caused by long-term large-dose administration of a single oil. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 Water-soluble tomato concentrate + Nannochloropsis oil reduced TC levels. Compared with the blank control group, *** indicates p < 0.001; compared with the model control group, # indicates p < 0.05, ### indicates p < 0.001; compared with the water-soluble tomato concentrate + krill oil group, $ indicates p < 0.05, $$ indicates p < 0.01.

[0048] Figure 2 Water-soluble tomato concentrate + Nannochloropsis oil reduced TG levels. Compared with the blank control group, *** indicates p < 0.001; compared with the model control group, # indicates p < 0.05, ### indicates p < 0.001; compared with the water-soluble tomato concentrate + krill oil group, $ indicates p < 0.05, $$ indicates p < 0.01.

[0049] Figure 3 Water-soluble tomato concentrate + Nannochloropsis oil reduced LDL-C levels. Compared with the blank control group, *** indicates p < 0.001; compared with the model control group, # indicates p < 0.05, and ### indicates p < 0.001.

[0050] Figure 4 The water-soluble tomato concentrate + fish oil reduced TC levels. Compared with the blank control group, *** indicates p < 0.001; compared with the model control group, # indicates p < 0.05, and ### indicates p < 0.001.

[0051] Figure 5 Water-soluble tomato concentrate + fish oil reduced TG levels. Compared with the blank control group, *** indicates p < 0.001; compared with the model control group, # indicates p < 0.05, and ### indicates p < 0.001.

[0052] Figure 6 Water-soluble tomato concentrate + fish oil lowered LDL-C levels. Compared with the blank control group, *** indicates p < 0.001; compared with the model control group, # indicates p < 0.05, and ### indicates p < 0.001. DETAILED DESCRIPTION

[0053] The embodiments of the present invention will be described in detail below with reference to the examples, but it will be understood by those skilled in the art that the following examples are merely illustrative of the present invention and should not be construed as limiting the scope of the invention. Where specific conditions are not specified in the examples, the methods were performed according to conventional conditions or the conditions recommended by the manufacturer. Where the manufacturers of the reagents or instruments are not specified, they are all conventional products that can be obtained commercially.

[0054] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in this specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0055] The optional scope of the terms "and / or", "or / and", and "and / or" used in this document includes any one of two or more related listed items, and also includes any and all combinations of the related listed items, and the said any and all combinations include any two related listed items, any more related listed items, or a combination of all related listed items.

[0056] In this disclosure, terms such as "first aspect" and "second aspect" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor as implicitly indicating the importance or quantity of the technical features indicated. Furthermore, terms such as "first" and "second" serve only as non-exhaustive enumeration and description and should not constitute a closed-ended limitation on quantity.

[0057] In the present invention, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0058] The percentage concentrations mentioned in the present invention, unless otherwise specified, refer to the final concentration, which refers to the percentage of the added component in the system after the addition of the component.

[0059] The water-soluble tomato concentrate (FF) used in the examples of the present invention was purchased from Provis Natural Products Co., Ltd.; other reagents and kits were purchased from commercial products on the market.

[0060] The following are specific embodiments:

[0061] 1. Experimental animals and model feed

[0062] 1.1 Experimental animals

[0063] 6-7 week old male SPF SD rats were housed in a barrier environment animal room with an ambient temperature of 20-26°C, a relative humidity of 30-70%, an air exchange rate ≥15 times / hour, and a light-dark cycle of 12-14 hours and a dark cycle of 12-10 hours.

[0064] 1.2 Model feed

[0065] The maintenance feed was supplemented with 20.0% sucrose, 15% lard, 1.2% cholesterol, and 0.2% sodium cholate, as well as appropriate amounts of casein, calcium hydrogen phosphate, and stone powder. Except for crude fat, the moisture, crude protein, crude fiber, crude ash, calcium, phosphorus, and calcium content of the model feed all met the national standards for maintenance feed.

[0066] Example 1:

[0067] This example provides a study on the lipid-lowering efficacy of water-soluble tomato concentrate and Nannochloropsis oil.

[0068] 1. Reagents

[0069] Nannochloropsis oil was purchased from Guangxi Xiaozao Agricultural Technology Co., Ltd.

[0070] 2. Experimental Grouping

[0071] Based on the preliminary experiments, the auxiliary lipid-lowering experiment was divided into 10 groups, namely blank control group, model control group, positive control group (lovastatin), FF (water-soluble tomato concentrate)-1, FF-2, krill oil, Pseudo-Nanococcus oil, FF+krill oil, FF-1+Pseudo-Nanococcus oil, and FF-2+Pseudo-Nanococcus oil.

[0072] 3. Experimental steps

[0073] 3.1 Grouping

[0074] Several SD rats that passed the adaptive observation were selected and randomly divided into two groups according to body weight (the first grouping). Ten rats were given a maintenance diet and included in the blank control group, and 80 rats were given a model diet and included in the model group. After the model group was given the model diet for 2 weeks, approximately 0.3 mL of blood was collected from the rats in the blank control group and the model group (through the anterior vena cava) without fasting. After serum separation, TC (total cholesterol), TG (triglycerides), LDL-C (low-density lipoprotein-cholesterol), and HDL-C (high-density lipoprotein-cholesterol) levels were measured using an automatic biochemical analyzer.

[0075] The rats were divided into two groups according to their serum TC levels, with 8 rats in each group. After grouping, there were no significant differences in body weight, TC, TG, LDL-C, and HDL-C between the model groups (model control group and test group).

[0076] 3.2 Modeling

[0077] After the model group was fed the model diet for 2 weeks, the model group showed significant differences in TC, TG, and LDL-C compared with the blank control group, indicating that the model was established. After grouping, the blank control group continued to be fed the maintenance diet, and the other groups continued to be fed the model diet.

[0078] 3.3 Administration

[0079] Each drug group was gavaged with the corresponding drug, while the blank control group and the model control group were given an equal volume of solvent, once a day for 45 consecutive days. The dose of the positive drug was 3.33 mg / kg body weight, the dose of FF-1 was 16 mg / kg body weight, the dose of FF-2 was 25 mg / kg body weight, the dose of krill oil was 167 mg / kg body weight, the dose of Pseudo-Nanococcus oil was 167 mg / kg body weight, the dose of FF+krill oil group was 192 mg / kg body weight, the dose of FF-1+Pseudo-Nanococcus oil group was 183 mg / kg, and the dose of FF-2+Pseudo-Nanococcus oil group was 192 mg / kg body weight.

[0080] 3.4 Index detection

[0081] Clinical observations were conducted 1 to 2 times a day during the experiment. Rats were weighed once a week during the drug administration period. One hour after the last drug administration, approximately 1 mL of blood was collected from the anterior vena cava of each group without fasting. After serum separation, TC, TG, LDL-C, and HDL-C levels were determined using an automatic biochemical analyzer. Rats were euthanized by drawing blood from the abdominal aorta after isoflurane inhalation anesthesia. The prepared serum was frozen at -80°C for future use.

[0082] 3.5 Data Analysis

[0083] The results were expressed as mean ± standard deviation. The inter-group comparisons were performed using the group t test. P < 0.05 indicated a significant difference, and P < 0.001 indicated an extremely significant difference.

[0084] 4. Results

[0085] As shown in Table 1, compared with the blank control group, the model control group showed significant increases in serum TC, TG, and LDL-C, while HDL-C was significantly decreased, indicating successful model establishment. Compared with the model control group, TC was significantly decreased in the FF-1 and FF-2 groups, indicating that the water-soluble tomato concentrate has the effect of lowering TC. TG and LDL-C did not change significantly. Compared with the model control group, TG was significantly decreased in the Pseudo-Nanococcus oil group, indicating that Pseudo-Nanococcus oil has the effect of lowering TG, while TC and LDL-C did not change significantly. Compared with the model control group, krill oil significantly decreased TG and LDL-C, indicating that krill oil has the effect of lowering TG and LDL, while TC did not change significantly. Compared with the model control group, TG and LDL-C were significantly decreased in the FF + krill oil group, while TC did not change significantly. Compared with the model control group, TC, TG, and LDL-C were significantly decreased in the FF-1 + Pseudo-Nanococcus oil group and the FF-2 + Pseudo-Nanococcus oil group, indicating that FF + Pseudo-Nanococcus oil has the effect of lowering TC, TG, and LDL-C.

[0086] Compared with the FF group alone that lowered TC and the Pseudo-Nanococcus oil group that lowered TG, both groups of FF+Pseudo-Nanococcus oil significantly lowered the levels of TC, TG and LDL-C; compared with the FF+krill oil group that only lowered the levels of TG and LDL-C, the intake of a lower dose of FF-1+Pseudo-Nanococcus oil significantly lowered the levels of TC, TG and LDL-C; FF-2+Pseudo-Nanococcus oil not only significantly lowered the levels of TC, TG, and LDL-C, but also lowered the levels of TC and TG more significantly. In other words, the water-soluble tomato concentrate+Pseudo-Nanococcus oil group had a better effect in assisting in lowering blood lipids.

[0087] Table 1 Effects of the test substances on four blood lipids in rats (mean ± standard deviation, n = 8)

[0088]

[0089] Note: Compared with the blank control group, *** indicates p < 0.001; compared with the model control group, # indicates p < 0.05, ### indicates p < 0.001; compared with FF + Nannochloropsis oil and FF + krill oil, $ indicates p < 0.05, $$ indicates p < 0.01.

[0090] As shown in Table 2, the calculated CDI drug interaction coefficients of the two groups of FF + Pseudochloropsis oil were less than 1 (indicating a synergistic effect). The calculation results of the Jin Zhengjun Q value method also showed that there was a synergistic effect between FF and Pseudochloropsis. Compared with the FF + krill oil group, which only had a synergistic effect / additive effect on TG, the two groups of FF + Pseudochloropsis oil of the present invention had a synergistic effect on TG, TC, and LDL-C, indicating that the combination of water-soluble tomato concentrate and Pseudochloropsis oil has a significant synergistic effect on assisting in lowering blood lipids.

[0091] Table 2 Calculation results of the synergistic effect of water-soluble tomato concentrate + Nannochloropsis oil on lowering blood lipids

[0092]

[0093] Note: CDI (Cell Difference Index) is the drug-drug interaction coefficient (CDI) = AB / A*B, where AB is the ratio of the two-drug combination group to the control group, and A or B is the ratio of the individual drug group to the control group. A CDI < 1 indicates synergy between the two drugs. Kim Jung-gyun's Q method: Q = Ea+b / (Ea+Eb-Ea*Eb), where Ea and Eb are the inhibition rates of drug A and drug B alone, respectively. The numerator represents the measured combined effect, and the denominator represents the expected combined effect. A Q of 0.85 ≤ Q < 1.15 indicates additive effects, and a Q of ≥ 1.15 indicates synergism.

[0094] Furthermore, regarding the dosage of the composition, the human equivalent dose of the present invention, at 167 mg / kg body weight in rats, is 998.66 mg (approximately 1 g) per day. Compared to the equivalent dose of Nannochloropsis oil alone, which only lowers triglycerides (TG), the present invention achieves synergistic reductions in TC, TG, and LDL-C. Compared to a daily intake of 2-4 g of conventional fish oil or high-purity EPA, the present composition significantly reduces the daily dosage while achieving superior results.

[0095] Example 2:

[0096] This example provides a study on the lipid-lowering efficacy of a combination of water-soluble tomato concentrate and fish oil.

[0097] 1. Reagents

[0098] Fish oil was purchased from Epax, Norway.

[0099] 2. Experimental Grouping

[0100] The experiment was divided into 10 groups, namely blank control group, model control group, positive control group (lovastatin), water-soluble tomato concentrate (FF)-1, water-soluble tomato concentrate (FF)-2, fish oil, krill oil, water-soluble tomato concentrate (FF) + krill oil, FF-1 + fish oil, and FF-2 + fish oil.

[0101] 3. Experimental steps

[0102] 3.1 Grouping

[0103] Several SD rats that passed the adaptive observation were selected and randomly divided into two groups based on body weight (the first grouping). Ten rats were given a maintenance diet and included in the blank control group, while 80 rats were given a model diet and included in the model group. After two weeks of feeding, approximately 0.3 mL of blood was collected from the anterior vena cava of the rats in the blank and model groups without fasting. The serum was separated and measured using an automated biochemical analyzer for TC, TG, LDL-C, and HDL-C levels.

[0104] The rats were randomly divided into a model control group, a positive control group, FF-1, FF-2, fish oil, krill oil, FF + krill oil, FF-1 + fish oil, and FF-2 + fish oil groups, with 8 rats in each group. No significant differences in body weight, TC, TG, LDL-C, or HDL-C were found between the model group (model control group) and the test group.

[0105] 3.2 Modeling

[0106] After the model group was fed the model diet for 2 weeks, the model group showed significant differences in TC, TG, and LDL-C compared with the blank control group, indicating that the model was established. After grouping, the blank control group continued to be fed the maintenance diet, and the other groups continued to be fed the model diet.

[0107] 3.3 Administration

[0108] Each drug group was gavaged with the corresponding drug, while the blank and model control groups received an equal volume of solvent, once daily for 45 consecutive days. The dose of the active drug was 3.33 mg / kg body weight, the dose of FF-1 was 25 mg / kg body weight, the dose of FF-2 was 42 mg / kg body weight, the dose of fish oil was 267 mg / kg body weight, the dose of krill oil was 267 mg / kg body weight, the dose of FF+krill oil group was 309 mg / kg body weight, the dose of FF-1+fish oil group was 292 mg / kg body weight, and the dose of FF-2+fish oil group was 309 mg / kg body weight.

[0109] 3.4 Index detection

[0110] Clinical observations were conducted 1 to 2 times a day during the experiment. Rats were weighed once a week during the drug administration period. One hour after the last drug administration, approximately 1 mL of blood was collected from the anterior vena cava of each group without fasting. After serum separation, TC, TG, LDL-C, and HDL-C levels were determined using an automatic biochemical analyzer. Rats were euthanized by drawing blood from the abdominal aorta after isoflurane inhalation anesthesia. The prepared serum was frozen at -80°C for future use.

[0111] 3.5 Data Analysis

[0112] The results were expressed as mean ± standard deviation. The inter-group comparisons were performed using the group t test. P < 0.05 indicated a significant difference, and P < 0.001 indicated an extremely significant difference.

[0113] 4. Results

[0114] As shown in Table 3 below, under the experimental conditions, the model control group showed significant increases in serum TC, TG, and LDL-C compared to the blank control group, while HDL-C was significantly decreased, indicating successful model establishment. Compared to the model control group, TC was significantly decreased in the FF-1 and FF-2 groups, demonstrating the efficacy of the water-soluble tomato concentrate in lowering TC. TG and LDL-C did not change significantly. Krill oil significantly decreased TG and LDL-C compared to the model control group, while TC did not change significantly. Fish oil significantly decreased TG and LDL-C compared to the model group, while TC did not change significantly. The FF + krill oil group significantly decreased TC, TG, and LDL-C compared to the model control group. The FF-1 + fish oil and FF-2 + fish oil groups significantly decreased TG, TC, and LDL-C compared to the model control group, with the FF-2 + fish oil group showing a superior effect.

[0115] Compared with the FF group alone that lowered TC and the fish oil group that lowered TG and LDL-C, both groups of FF + fish oil significantly reduced the levels of TC, TG and LDL-C; compared with the FF + krill oil group, the group that consumed a lower dose of FF-1 + fish oil significantly reduced the levels of TC, TG and LDL-C, and the group that consumed the same dose of FF-2 + fish oil more significantly reduced the levels of TC, TG, and LDL-C, that is, the water-soluble tomato concentrate + fish oil group had a more significant effect in lowering blood lipids.

[0116] Table 3 Effects of the test substances on four blood lipids in rats (mean ± standard deviation, n = 8)

[0117]

[0118]

[0119] Note: Compared with the blank control group, *** indicates p < 0.001; compared with the model control group, # indicates p < 0.05, ### indicates p < 0.001; compared with FF + fish oil and FF + krill oil, $ indicates p < 0.05, $$ indicates p < 0.01.

[0120] As shown in Table 4 below, based on the calculation results of the CDI two-drug action coefficient and the Jin Zhengjun Q value method, it is shown that the water-soluble tomato concentrate combined with fish oil can synergistically enhance the effect and assist in lowering blood lipids.

[0121] Table 4 Calculation results of Jin Zhengjun's Q value method

[0122]

[0123] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. Use of a composition in preparing a product for assisting in lowering blood lipids, characterized in that: The composition consists of water-soluble tomato concentrate and Nannochloropsis oil in a mass ratio of 2 to 3:

20. The product is a medicine or a health food.

2. A composition having the effect of assisting in lowering blood lipids, characterized in that: The invention is composed of water-soluble tomato concentrate and microalgae oil in a mass ratio of 2-3:20; the auxiliary blood lipid lowering method is to lower triglycerides, cholesterol and low-density lipoprotein in the blood.

3. Use of a composition in preparing a product for assisting in lowering blood lipids, characterized in that: The composition consists of water-soluble tomato concentrate and fish oil in a mass ratio of 3 to 5:32, and the product is a medicine or a health food.

4. A composition having the effect of assisting in lowering blood lipids, characterized in that: The invention is composed of water-soluble tomato concentrate and fish oil in a mass ratio of 3-5:32; the auxiliary blood lipid lowering method is to lower triglycerides, cholesterol and low-density lipoprotein in the blood.

5. The use according to claim 1 or claim 3, characterized in that: The product also contains excipients acceptable to medicines or health foods; the dosage forms of the product are: tablets, soft capsules, hard capsules, powders, oral liquid preparations, gels, and pills.

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