Preparation method and application of medicine-food homologous compound with weight-losing and lipid-lowering effects

Abstract

The invention relates to a preparation method and application of a medicine-food homologous compound with weight-losing and lipid-lowering effects. According to the present invention, the weight of the obese mouse can be reduced by 23.23% at most, the serum total cholesterol is reduced, the leptin secretion is reduced, AST (aspartate transaminase) and ALT (alanine transaminase) have no significant difference compared to the model mouse, the volume of epididymal fat and inguinal fat cells is reduced, the number of cells in unit area is significantly increased, the fatty liver sample is relieved, the TMEM26 gene expression in the epididymal fat is significantly increased, and the weight of the obese mouse can be significantly reduced; the expression quantity of the UCP1 gene in brown fat is obviously increased. The traditional Chinese medicine composition adopts medicinal and edible substances as raw materials, is widely applicable to people, is more suitable for prevention and treatment of chronic diseases, is safe and effective, and causes little damage to liver and kidney after long-term use.

Description

Technical Field

[0001] The present invention relates to the field of food technology, and in particular to a preparation method and application of a medicine-food compound with weight-loss and lipid-lowering effects. Background Art

[0002] Obesity has become one of the most serious global public health challenges of our time. With the development of society and the accelerated pace of life, people's dietary patterns have shifted. Traditional diets are gradually being replaced by high-salt, high-fat, and high-sugar fast food. Sedentary lifestyles are leading to increased sedentary time, and social pressures can also trigger emotional eating. These underlying factors have contributed to the continued rise in global obesity rates. Obesity is not only a physical issue; it can also lead to a variety of metabolic diseases such as diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Obesity can cause damage to the metabolic and cardiovascular systems, has been linked to various cancers, and can impair neurological function, significantly impacting people's lives.

[0003] The majority of weight loss drugs currently on the market are GLP-1 receptor agonists, lipase inhibitors, and central appetite regulators. These drugs have limitations, including the tendency for patients to experience gastrointestinal reactions such as nausea and vomiting, raising questions about their long-term safety. Most drugs fail to fundamentally regulate dietary behavior and energy metabolism, leading to weight rebound after discontinuation. Furthermore, they are not suitable for a wide range of patients, and most have restrictions on the patient's BMI. Overall, while weight loss drugs have achieved breakthroughs in weight loss, they still suffer from significant side effects, a high risk of weight rebound, and a limited patient population.

[0004] Traditional Chinese medicine formulas are complex and their safety is questionable. For example, long-term consumption of senna leaves can lead to intestinal dysfunction and decreased intestinal motility, which can cause stubborn constipation. It can also cause metabolic imbalances and exacerbate electrolyte loss. Alisma orientalis contains alismol A, which is nephrotoxic with long-term use, and its strong diuretic effect can cause hypokalemia, which can easily damage the digestive system in patients with spleen deficiency. Cassia seed can also cause intestinal damage, electrolyte imbalances, and increase the metabolic burden on the liver. Nuciferine, the core ingredient of lotus leaves, can damage the digestive tract, cause diarrhea, increase the metabolic burden on the liver and kidneys, and may induce arrhythmias when used in combination with diuretic Chinese herbal ingredients. This shows that although Chinese herbal components have been used in the field of weight loss, their complex composition can cause uncontrollable side effects, and their safety remains a challenge, requiring rational combination and the selection of selected medicinal materials.

[0005] Food and medicine substances refer to natural plants, animals and minerals that have been verified by long-term practice to have both nutritional functions and pharmacological activities and can be safely used in food and medicine. It emphasizes the natural homology of food and medicine, has the idea of ​​preventing disease before it occurs, and hopes to regulate the physical constitution through daily diet and achieve a dynamic balance of "food nourishing the positive nature and medicine attacking the negative nature".

[0006] The medicine-food homologous formula has been applied in weight loss, for example, the compound composed of curcuma, cassia seed, hawthorn, plantain, senna leaf, white kidney bean extract, L-carnitine tartrate is given to obese rats for 6 weeks, which can reduce the weight of rats by 4.75%; the compound water extract composed of raw astragalus, prepared atractylodes, cassia bark, dried tangerine or orange peel, lotus leaf, raw hawthorn, kelp, turmeric, fried radish seed and raw pine pollen is given to obese rats for 8 weeks, which can reduce the weight of rats by 9.87%; the Bi Sheng Gong brand Poria cocos and alisma tablet is given to obese rats for 6 weeks, which can reduce the weight of rats by 8.15%; the traditional Chinese medicine compound composed of five-finger fig, Poria cocos, coix seed, hawthorn, licorice, lotus leaf, cassia seed, panax notoginseng root, bitter gourd, orange peel and Yunnan red tea is given to obese rats for 6 weeks, which can reduce the weight of rats by 9.5%. Therefore, although the existing medicine-food homologous formula has high safety, the animal experiment shows that the effect is weaker than that of chemical drugs. SUMMARY

[0007] In order to solve the problems of obvious side effects, limited application population and poor effect of weight loss products in the prior art, the present application provides a medicine-food homologous composition with weight loss and lipid-lowering effect, a preparation method and its application.

[0008] In one aspect, the present application provides a weight loss and lipid-lowering medicine-food homologous composition, which is made of raw medicinal materials in the following proportions: coix seed 0-5 parts, dried tangerine or orange peel 1-6 parts, longan arillus 0-6 parts, medlar 1-7 parts, Fructus Mume 2-10 parts, hawthorn 2-11 parts, and raspberry 4-17 parts.

[0009] Preferably, the composition is made of raw medicinal materials in the following proportions: dried tangerine or orange peel 2 parts, medlar 2 parts, Fructus Mume 3 parts, hawthorn 3 parts, and raspberry 12 parts.

[0010] In a second aspect, the present application provides a preparation method of the weight loss and lipid-lowering medicine-food homologous composition, which comprises the following steps: step (1), preparing raw materials according to the proportions; step (2), taking dried tangerine or orange peel, medlar, Fructus Mume, hawthorn and longan arillus, adding water and boiling slightly, filtering to obtain supernatant; adding drinking water to the residue and repeating the process once; combining the filtrates, rotary evaporating to the extract, and freeze-drying to obtain powder; step (3), taking raspberry and coix seed, adding water and boiling slightly, filtering to obtain supernatant; adding drinking water to the residue and repeating the process once; combining the filtrates, rotary evaporating to the extract, and freeze-drying to obtain powder; and step (4), mixing the two powders to obtain the weight loss and lipid-lowering medicine-food homologous composition.

[0011] Further, in step (2), the solid-liquid ratio is 1:13-1:20, and the boiling time is 10-20 min.

[0012] Further, in step (3), the solid-liquid ratio is 1:13-1:20, and the boiling time is 1-2 h.

[0013] In a third aspect, the present invention provides a weight-loss and lipid-lowering preparation, which is composed of the weight-loss and lipid-lowering medicinal and edible composition and a pharmaceutically acceptable carrier.

[0014] Furthermore, the preparation is one of granules, tablets, powders, capsules, oral liquids, injections, sprays, aerosols, powder sprays, emulsions, nasal drops, suppositories, pills, microsphere preparations or tinctures.

[0015] In a third aspect, the present invention provides the weight-loss and lipid-lowering medicinal and edible composition, the weight-loss and lipid-lowering medicinal and edible composition prepared by the method, and the use of the weight-loss and lipid-lowering preparation in the preparation of weight-loss and lipid-lowering drugs or weight-loss and lipid-lowering health products.

[0016] The present invention has the following beneficial effects: (1) The present invention uses medicinal and edible substances as raw materials. Compared with the Western medicine and traditional Chinese medicine weight loss drugs on the market, the present invention has fewer toxic and side effects, is less likely to cause gastrointestinal discomfort, and has a significant weight loss effect. The present invention can achieve a maximum weight loss of about 23.23% in obese mice, reduce serum total cholesterol and leptin levels, and reduce fat cell volume. The AST and ALT results show that it has no liver and kidney toxicity and is safe and effective.

[0017] (2) The present invention uses medicinal and edible substances as raw materials, is suitable for a wide range of people, is more suitable for the prevention and treatment of chronic diseases, is safe and effective, and causes little damage to the liver and kidneys when taken for a long time. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a diagram of the Chinese medicine and food homologous raw material of the present invention; Figure 2 This is a record of the dynamic changes in the body weight of mice after ten weeks of drug administration; Figure 3 This is a graph showing serum AST activity determination; Figure 4 This is a graph showing the determination of serum ALT activity; Figure 5 It is a chart for measuring serum total cholesterol content; Figure 6 This is a graph showing the determination of serum leptin levels; Figure 7 are representative images of H&E-stained liver sections; Figure 8 are representative images of H&E-stained epididymal fat sections; Figure 9 are representative images of H&E-stained inguinal fat sections; Figure 10 It is a statistical chart of the number of fat cells per unit area of ​​epididymal fat; Figure 11 It is a statistical graph of the number of fat cells per unit area of ​​inguinal fat; Figure 12 Epididymal fat TMEM26 Gene expression graph; Figure 13 In brown fat UCP1 Gene expression graph. DETAILED DESCRIPTION

[0019] The technical solutions of the present invention will be further described in detail below in conjunction with specific embodiments of the present invention and the accompanying drawings. Please note that the embodiments described below are only some embodiments of the present invention, do not cover all, and do not limit the present invention in any form.

[0020] Example 1: Preparation of a medicinal and edible compound with weight loss and lipid-lowering effects: Prepare raw materials, such as Figure 1 2 parts dried tangerine peel, 2 parts wolfberry, 3 parts black plum, and 3 parts hawthorn were immersed in water and simmered for 20 minutes. The filtrate was collected and the residue was boiled in water for 20 minutes. The two filtrates were combined and rotary evaporated to a paste-like consistency. The mixture was freeze-dried to obtain a powder. 12 parts raspberry were added to 180 parts water and simmered for 2 hours. The filtrate was collected and the residue was boiled in water for 2 hours. The two filtrates were combined and rotary evaporated to a paste-like consistency. The mixture was freeze-dried to obtain a powder. The two powders were mixed in a 1:1 ratio to obtain the compound powder. The resulting powder was dissolved in 0.5% CMC-Na solution to obtain the compound preparation for later use.

[0021] experiment Main instruments and equipment: -80℃ refrigerator; scanning microtome; centrifuge; rotary evaporator; freeze dryer; grinder; fluorescence quantitative PCR instrument; AST, ALT, T-CHO, and leptin assay kits.

[0022] Animal Origin: SPF healthy mature male C57BL / 6 mice, 6-8 weeks old.

[0023] Modeling: C57BL / 6 mice were adaptively fed in an SPF environment for 7 days with a 12-h light-dark cycle and unlimited food and water. After the adaptation period, they were randomly divided into a normal diet group (n=6) and a high-fat diet group (n=27). They were given earrings with number tags and given maintenance feed (10% fat) and high-fat feed (60% fat), respectively. They were weighed every three days. After 2 weeks, 9 obesity-resistant mice were eliminated from the high-fat diet group based on their body weight.

[0024] Experimental groups: ① Control group: fed with ordinary feed and gavaged with an equal amount of 0.5% CMC-Na solution ② Model group: fed with high-fat diet and gavaged with an equal amount of 0.5% CMC-Na solution ③ Compound preparation group: fed with high-fat diet and given compound preparation by gavage ④ Positive drug group: fed with high-fat diet, and gavage with orlistat (dissolved in 0.5% CMC-Na) 1. Changes in mouse weight Weigh the mice once a week and record the weight changes of each group. Figure 2 As shown in the figure, after the modeling, the weight of mice in the model group, compound group, and positive drug group were significantly different from those in the blank group ( p<0.05 ), indicating that the obesity model of high-fat diet was successfully established. After 10 weeks of administration, the body weight of mice in the blank group was significantly different from that in the model group ( p<0.01 ), the weight of the compound group decreased significantly compared with the model group ( p<0.001 ), while there was no significant difference compared with the blank group. The body weight of the positive drug group decreased significantly compared with the model group ( p<0.05 ), but their weight loss rate was lower than that of the compound preparation group, indicating that the Chinese herbal compound preparation does have significant weight loss and lipid-lowering effects, and its weight loss effect is better than that of orlistat, a commonly used chemical weight loss drug on the market.

[0025] After ten weeks of administration, the weight loss rate of mice was calculated. The analysis results showed that the compound preparation could achieve a 23.23% weight loss in mice, and orlistat could achieve a 13.32% weight loss in mice.

[0026] , where W 模型 represents the average weight of mice in the model group, W 用药 Represents the average body weight of mice in the compound preparation group or positive drug group.

[0027] 2. Serum-related index detection After 10 weeks of dosing, the mice's eyeballs were removed and blood was collected in centrifuge tubes. The blood was allowed to stand at room temperature for 1 hour and then centrifuged at 3000 rpm for 10 minutes at 4°C. The serum was separated and stored in a -80°C freezer. AST, ALT, T-CHO, and leptin levels were determined using kits. Specific assay procedures were described in the kit instructions.

[0028] like Figure 3-4 As shown, the AST and ALT levels in the model group were significantly higher than those in the blank group, which may be due to partial liver and kidney damage caused by obesity. The AST and ALT levels in the compound group were significantly lower than those in the model group, and there was no significant difference in AST and ALT between the positive drug and the model group, indicating that the compound of the present invention had no obvious damage to the liver and kidneys, and had less toxic side effects on the liver and kidneys than the positive drug.

[0029] like Figure 5 As shown, the serum total cholesterol level in the model group was significantly higher than that in the blank group ( p<0.001), the serum total cholesterol content in the compound group was significantly lower than that in the model group ( p<0.001 ), indicating that the compound preparation can lower serum total cholesterol and has lipid-lowering effect.

[0030] like Figure 6 As shown in Figure 2, the serum leptin content in the model group was significantly higher than that in the blank group ( p<0.05 ), the leptin produced by fat cells is positively correlated with body fat mass. Obese mice will over-secrete leptin, leading to leptin resistance. The serum leptin content in the compound group was significantly lower than that in the model group ( p<0.05 ), indicating that the compound can reduce fat accumulation, improve leptin sensitivity, and normalize leptin levels.

[0031] 3. H&E staining of mouse liver, epididymal fat, and inguinal fat After 10 weeks of administration, the liver, epididymal fat, and inguinal fat of the mice were fixed in 4% paraformaldehyde, embedded in paraffin, and sliced. The slices were stained with hematoxylin-eosin, dehydrated, and mounted. The images were scanned using a scanning microtome. Figure 7-9 shown.

[0032] like Figure 7 In the liver sections of the model group, fat droplets accumulated in the hepatocytes, round vacuoles appeared, and fat was diffusely distributed, showing a fatty liver-like appearance. The hepatocytes of the compound group were regular polygons. Compared with the model group, there was no obvious lipid accumulation, indicating that the compound group can alleviate fatty liver and have a lipid-lowering effect.

[0033] like Figure 8 and Figure 9 The volume of epididymal fat and inguinal fat cells in the model group increased, while the volume of fat cells in the compound preparation group was significantly reduced compared with the model group.

[0034] Observe the stained sections and count the cells in the epididymal fat and inguinal fat per unit area. The results are as follows: Figure 10 and Figure 11 As shown in the figure, the number of epididymal fat per unit area in the model group decreased, and the volume of single cells increased. After gavage with the compound preparation, the number of fat cells per unit area increased significantly ( p<0.01 ), the volume of single cells decreased, indicating that the compound preparation can promote lipid degradation and reduce fat accumulation.

[0035] 4. Determination of brown fat and epididymal fat-related gene expression Take 20-40 mg of mouse brown fat or epididymal fat, place it in a sterilized centrifuge tube with 4 pre-placed grinding steel balls, add 1 ml RNA isoplus, place it in a pre-cooled grinder and grind for 10 min until the tissue is homogenized, add 200ul chloroform, centrifuge and take the supernatant to extract RNA with an equal amount of isopropanol, measure the RNA concentration, and then reverse transcribe according to the reverse transcription kit instructions to obtain cDNA, mix SYBR enzyme, cDNA and primers according to the proportion, the primer sequence is shown in Table 1, and the internal reference in this experiment is GAPDH , and the final gene expression is represented by 2 -△△CT . The expression of TMEM26 gene and UCP1 gene was analyzed by quantitative fluorescent PCR experiment, and the results are shown in Figure 12 and Figure 13 As can be seen from the figure, compared with the model group, the expression of mice administered with the compound of the present application UCP1 significantly increased (P<0.01). p<0.001 . UCP1 is a direct marker of brown fat thermogenesis activation, and after administration UCP1 expression is up-regulated, indicating that the compound of the present application can promote energy consumption by activating the thermogenic effect of brown fat, induce white fat browning, and thus achieve the effect of weight loss and lipid reduction.

[0036] Table 1 Primer sequence

[0037] All data were analyzed for significance using SPSS, and were plotted and analyzed using Graphpad Prism and AI. The data are expressed as mean ± standard error of the mean, and the comparison between groups used one-way ANOVA (ANOVA), p<0.05 , and it was considered to have statistical difference. #, ##, ### represent the comparison between the model group and the blank group p<0.05, p<0.01, p<0.001 . , , , respectively p<0.05, p<0.01, p<0.001 .

[0038] Example 2: Preparation of a homologous compound with weight loss and lipid reduction effect: Prepare the raw materials, such as Figure 11 part dried tangerine peel, 1 part wolfberry, 2 parts black plum, and 2 parts hawthorn were immersed in water and simmered for 20 minutes. The filtrate was collected and the residue was boiled in water for 20 minutes. The two filtrates were combined and rotary evaporated to a paste-like consistency. The mixture was freeze-dried to obtain a powder. 4 parts raspberry were added to 180 parts water and simmered for 2 hours. The filtrate was collected and the residue was boiled in water for 2 hours. The two filtrates were combined and rotary evaporated to a paste-like consistency. The mixture was freeze-dried to obtain a powder. The two powders were mixed in a 1:1 ratio to obtain the compound powder. The resulting powder was dissolved in 0.5% CMC-Na solution to obtain the compound preparation for later use.

[0039] Example 3: Preparation of a medicinal and edible compound with weight loss and lipid-lowering effects: Prepare raw materials, such as Figure 1 6 parts of dried tangerine peel, 7 parts of wolfberry, 10 parts of black plum, 11 parts of hawthorn, and 6 parts of longan pulp were added to water to submerge the herbs and simmered for 20 minutes. The filtrate was collected, the residue was boiled in water for 20 minutes, the two filtrates were combined, rotary evaporated to a paste, and freeze-dried to obtain a powder. 17 parts of raspberry and 5 parts of coix seed were added to 180 parts of water and simmered for 2 hours. The filtrate was collected, the residue was boiled in water for 2 hours, the two filtrates were combined, rotary evaporated to a paste, and freeze-dried to obtain a powder. The two powders were mixed in a 1:1 ratio to obtain the compound powder. The resulting powder was dissolved in 0.5% CMC-Na solution to obtain the compound preparation, which was set aside.

[0040] Comparative Example 1: Without adding wolfberry, other components and preparation methods were the same as in Example 1. The experiment was carried out according to Example 1, and the weight of mice was analyzed.

[0041] Comparative Example 2:

[0042] Without adding raspberry, other components and preparation methods were the same as in Example 1. The experiment was carried out according to Example 1, and the weight of mice was analyzed.

[0043] The weight loss results for mice in each of the Examples and Comparative Examples are shown in Table 2. The results indicate that the components of the present invention can achieve a maximum weight loss of 23.23% in mice. Comparative Example 1, a formula without wolfberry, and Comparative Example 2, a formula without raspberry, achieved significantly lower weight loss rates than the formula of the present invention. This demonstrates that the components of the present invention exhibit a synergistic effect in achieving weight loss.

[0044] Table 2 Weight loss results of mice in various examples .

Claims

1. A weight-loss and lipid-lowering medicinal and edible composition, characterized in that: The medicine is prepared from the following raw materials in parts by weight: 0-5 parts of coix seed, 1-6 parts of dried tangerine peel, 0-6 parts of longan pulp, 1-7 parts of wolfberry, 2-10 parts of black plum, 2-11 parts of hawthorn and 4-17 parts of raspberry.

2. The weight-loss and lipid-lowering medicinal and edible composition according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 2 parts of dried tangerine peel, 2 parts of wolfberry, 3 parts of black plum, 3 parts of hawthorn and 12 parts of raspberry.

3. A method for preparing the weight-loss and lipid-lowering medicinal and edible composition according to any one of claims 1 to 2, characterized in that: The method comprises the following steps: step (1), preparing raw materials in proportion; step (2), taking tangerine peel, wolfberry, black plum, hawthorn, and longan pulp, adding water to slightly boil, filtering and taking the supernatant; adding drinking water to the filter residue and repeating the process once; combining the two filtrates, rotary evaporating to an extract form, and freeze-drying to obtain a powder; step (3), taking raspberry and coix seed, adding water to slightly boil, filtering and taking the supernatant; adding drinking water to the filter residue and repeating the process once; combining the two filtrates, rotary evaporating to an extract form, and freeze-drying to obtain a powder; and step (4) mixing the two powders to obtain a weight-loss and lipid-lowering medicinal and edible composite.

4. The method according to claim 3, characterized in that In step (2), the material-liquid ratio is 1:13-1:20, and the mixture is slightly boiled for 10-20 minutes.

5. The method according to claim 3, characterized in that In step (3), the material-liquid ratio is 1:13-1:20, and the mixture is gently boiled for 1-2 hours.

6. A weight loss and lipid-lowering preparation, characterized in that: The invention is composed of the weight-loss and lipid-lowering medicine-food composition according to claim 1 or 2 and a pharmaceutically acceptable carrier.

7. The weight loss and lipid-lowering preparation according to claim 6, characterized in that The preparation is one of granules, tablets, powders, capsules, oral liquids, injections, sprays, aerosols, powder sprays, emulsions, nasal drops, suppositories, pills, microsphere preparations or tinctures.

8. Use of the weight-loss and lipid-lowering medicinal and edible composition according to any one of claims 1-2, the weight-loss and lipid-lowering medicinal and edible composition prepared by the method according to any one of claims 3-5, and the weight-loss and lipid-lowering preparation according to any one of claim 6 in the preparation of weight-loss and lipid-lowering drugs or weight-loss and lipid-lowering health products.

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