Pharmaceutical composition for preventing and / or treating obesity, fatty liver and hyperglycemia, pharmaceutical preparation and application

Abstract

The invention provides a pharmaceutical composition for preventing and / or treating obesity, fatty liver and hyperglycemia, a pharmaceutical preparation and application, and particularly belongs to the technical field of medicine. The pharmaceutical composition for preventing and / or treating obesity, fatty liver and hyperglycemia disclosed by the invention comprises berberine and 20 (S)-protopanoxadiol. The natural pharmaceutical composition disclosed by the invention has a remarkable anti-obesity effect, can be used for remarkably reducing blood sugar and improving the fat accumulation degree in a body, and has an effect of treating fatty liver, so that the BBR-PPD composition has a remarkable effect in the aspects of preventing and / or treating obesity and reducing blood sugar and blood fat.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine, and particularly relates to a pharmaceutical composition, a pharmaceutical preparation and an application for preventing and / or treating obesity, fatty liver and hyperglycemia. Background Art

[0002] Obesity is a chronic metabolic disease caused by excessive accumulation and abnormal distribution of body fat. The characteristics of obesity are the expansion of adipose tissue mass. There are two types of adipose tissue: white adipose tissue (WAT) stores energy and brown adipose tissue (BAT) consumes energy. BAT has a particularly important function in newborns, but gradually disappears or becomes inactive with age. WAT is not only the largest energy reserve in the human body, but also the largest endocrine organ in the human body (Shufen Li, Xi Li, Leptin in normal physiology and leptin resistance, Science Bulletin, Volume 61, Issue 19, 2016, Pages 1480 - 1488). Controlling the weight of overweight and obese patients has become an urgent clinical need. Deeply exploring the pathogenesis of obesity and finding safe and effective treatment strategies and drugs are of great significance for the prevention and treatment of obesity.

[0003] Among the early anti - obesity drugs, some drugs such as benfluorex, when taken for a long time, are prone to cause serious heart complications (Weill, A., M., Tuppin, P., Fagot, J.-P., Neumann, A., Simon, D., Ricordeau, P., Montastruc, J.-L. and Allemand, H. (2010), Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus. Pharmacoepidem. Drug Safe., 19: 1256 - 1262). Orlistat is an anti - obesity drug approved by the State Drug Administration of China. However, as a lipase inhibitor, it is difficult to meet the needs of the domestic obese population in terms of efficacy and has many adverse reactions at the same time. In addition, the long - term weight control drugs approved by the FDA also have many adverse reactions and side effects, such as gastrointestinal discomfort, kidney lesions and the risk of carcinogenesis, etc. Therefore, some weight control drugs have been withdrawn from the market. The safety and long - term efficacy of drugs are particularly important. In order to effectively prevent and control obesity, there is a current need to develop a new anti - obesity drug with low toxicity and side effects and high safety.

[0004] Currently, there is a composition of Panax notoginseng total saponin extract and Coptis chinensis total alkaloids, which can achieve clinical treatment of lipid metabolism disorders and arteriosclerosis through blood lipid regulation function. However, since it is simplified from a natural product compound preparation: Compound Zhenshu Lipid Regulating Recipe (patent number: 200410051250.4), the ingredients are complex and the specific mechanism of the effective ingredients is unclear, which will affect the stability of the clinical efficacy of the product. At the same time, its relatively simple preparation process, the effective ingredients in the compound are not purified, and it is easy to contain more impurities, and the dosage is large, resulting in less than ideal patient compliance. At the same time, it mainly reduces the problem of metabolic disorders by regulating blood lipids, and does not involve obesity (a plant extract composition for preventing and treating lipid metabolism disorders and its preparation method, patent number: 201110008007.4) (a plant extract composition for preventing and treating arteriosclerosis and its preparation method, patent number: 201110026907.1). There is also a natural medicine composition for treating diabetes: ginseng stem and leaf saponins, red ginseng and coptis root. The combination of the three has a significant function of lowering blood lipids, can regulate the secretory function of the pancreas, protect the liver and kidneys, and thus achieve the effect of treating diabetes. Because it is a combination of active ingredients of natural products, its toxic and side effects are significantly lower than those of Western medicine, but it is a combination of multiple ingredients, and the specific effective ingredients are unclear, and the patient's compliance is not strong. Therefore, it is necessary to find the specific ingredients that lower blood lipids and blood sugar, screen the ingredients based on the mechanism of action, enhance the efficacy, and reduce patient consumption (a natural product composition for treating diabetes and its preparation, patent number: 201210283396.6).

[0005] Natural products are safe and effective, with few toxic and side effects, and they exert their efficacy at multiple targets. They have a very broad market prospect for the treatment of obese and overweight patients. Among the weight loss drugs currently approved for clinical trials in China, there are only two types of natural product preparations, namely Qiling Wenshen Xiaonang Granules and Zexie Jiangzhi Granules. It can be seen that the research on natural products in China is receiving more and more attention, but in the existing technology, natural products for the treatment of obesity are mainly prescriptions, with several or even more than a dozen flavors. Both the production cost and the patient's consumption cost are very huge, and the supply and demand are seriously insufficient. At present, there is still a lack of effective drugs with clear active substances for the prevention and / or treatment of obesity, fatty liver and hyperglycemia. Summary of the invention

[0006] The object of the present invention is to provide a pharmaceutical composition, pharmaceutical preparation and application for preventing and / or treating obesity, fatty liver and hyperglycemia. The pharmaceutical composition of the present invention contains berberine and 20(S)-protopanaxadiol as active substances, which can suppress appetite, reduce body weight, and achieve effective prevention and treatment of obesity.

[0007] The invention provides a pharmaceutical composition for preventing and / or treating obesity, fatty liver and hyperglycemia, comprising berberine and 20(S)-protopanaxadiol.

[0008] Preferably, in the pharmaceutical composition, the mass ratio of berberine to 20(S)-protopanaxadiol is (8-3):1.

[0009] Preferably, in the pharmaceutical composition, the mass ratio of berberine to 20(S)-protopanaxadiol is (5-3):1.

[0010] Preferably, the source of berberine includes chemical synthesis or extraction from plants; the source of 20(S)-protopanaxadiol includes Panax notoginseng stems and leaves, ginseng stems and leaves or American ginseng stems and leaves.

[0011] Preferably, the purity of the berberine raw material medicine is 50-100%; the purity of the 20(S)-protopanaxadiol raw material medicine is 50-100%.

[0012] The present invention also provides a pharmaceutical preparation for preventing and / or treating obesity, fatty liver and hyperglycemia, comprising the pharmaceutical composition described in the above technical solution and a pharmaceutically acceptable carrier or excipient.

[0013] Preferably, the type of the pharmaceutical preparation includes an oral preparation; the oral preparation includes capsules, tablets, granules, powders, pills, dripping pills, sustained-release and controlled-release preparations, oral liquids, mixtures or syrups.

[0014] Preferably, the excipient includes any one or more of lubricants, fillers, binders and disintegrants.

[0015] The present invention also provides the use of the pharmaceutical composition described in the above technical solution in the preparation of a drug for preventing and / or treating obesity, fatty liver and hyperglycemia.

[0016] The present invention also provides the use of the pharmaceutical composition described in the above technical solution in the preparation of a product for suppressing appetite, reducing body weight, lowering blood lipid and lowering blood sugar.

[0017] The present invention provides a pharmaceutical composition for preventing and / or treating obesity, fatty liver and hyperglycemia. The present invention selects more representative and multi-target natural products, namely berberine (BBR) and 20(S)-protopanaxadiol (PPD), as the pharmaceutical composition. The raw materials are natural and the components are clear. It can achieve the treatment of obesity, and has the effects of reducing blood lipid and blood sugar, and realizes the treatment of fatty liver. The test results show that after long-term intragastric administration of the natural pharmaceutical composition of the present invention to obese model mice induced by high-fat diet, the body weight of the mice is significantly improved, and there is a significant anti-obesity effect compared with the single-drug administration group. The pharmaceutical composition of the present invention can significantly reduce fasting blood glucose, lower the levels of triglyceride (TG), total cholesterol (CHO), low-density lipoprotein cholesterol (LDL-C), and increase the level of high-density lipoprotein cholesterol (HDL-C), and improve the degree of fat accumulation in the body, and has good curative effects in the treatment of obesity and reducing blood lipid and blood sugar. High-fat diet induces fatty liver in SD rats. After intragastric administration, it can effectively inhibit the appetite of rats, reduce the active food intake of rats, and cause the body weight of rats to decrease; the liver index of rats in the pharmaceutical composition group recovers best; the results of serum index determination show that the BBR-PPD group has better blood lipid-lowering efficacy compared with the PPD group and the BBR group. The BBR-PPD group can significantly improve the serum glucose level, has an obvious hypoglycemic effect, and the BBR-PPD group has the efficacy of treating fatty liver and improves the accumulation of liver fat. The results of the BBR-PPD composition on the photoperiod-induced obesity model of Microtus brandti show that the combination of the BBR-PPD natural product composition can effectively improve the body's metabolic level, and then improve the accumulation of liver fat. Therefore, the BBR-PPD composition has excellent effects in preventing and / or treating obesity and reducing blood sugar and blood lipid. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0019] Figure 1 It is a verification diagram of the animal model provided in Example 1 of the present invention;

[0020] Figure 2 It is a result diagram of the effect of the BBR-PPD natural pharmaceutical composition (the ratio is 4:1, that is, BBR is 400 mg / kg and PPD is 100 mg / kg) provided in Example 1 of the present invention on the weight change rate of DIO mice after intervention;

[0021] Figure 3Results graph of the effect of the BBR-PPD natural medicine composition provided in Example 1 of the present invention (ratio 4:1, i.e., BBR is 400 mg / kg and PPD is 100 mg / kg) on the food intake of DIO mice;

[0022] Figure 4 Results graph of the effect of the BBR-PPD natural medicine composition provided in Example 1 of the present invention (ratio 4:1, i.e., BBR is 400 mg / kg and PPD is 100 mg / kg) on the fasting blood glucose of DIO mice;

[0023] Figure 5 Results graph of the effect of the BBR-PPD natural medicine composition provided in Example 1 of the present invention (ratio 4:1, i.e., BBR is 400 mg / kg and PPD is 100 mg / kg) on the blood lipid levels of DIO mice; wherein, A is the TG results graph; B is the CHO results graph; C is the HDL-C results graph; D is the LDL-C results graph;

[0024] Figure 6 Results graph of the effect of the BBR-PPD natural medicine composition provided in Example 1 of the present invention (ratio 4:1, i.e., BBR is 400 mg / kg and PPD is 100 mg / kg) on the epididymal fat index of DIO mice;

[0025] Figure 7 Results graph of the effect of the BBR-PPD natural medicine composition provided in Example 1 of the present invention (ratio 4:1, i.e., BBR is 400 mg / kg and PPD is 100 mg / kg) on the perirenal fat index of DIO mice;

[0026] Figure 8 Results graph of the effect of the BBR-PPD natural medicine composition provided in Example 1 of the present invention (ratio 4:1, i.e., BBR is 400 mg / kg and PPD is 100 mg / kg) on the peritoneal fat index of DIO mice;

[0027] Figure 9 Results graph of the effect of the BBR-PPD natural medicine composition provided in Example 2 of the present invention (ratio 4:1, i.e., BBR is 400 mg / kg and PPD is 100 mg / kg) on the body weight of SD rat fatty liver models;

[0028] Figure 10 Results graph of the effect of the BBR-PPD natural medicine composition provided in Example 3 of the present invention (ratio 4:1, i.e., BBR is 400 mg / kg and PPD is 100 mg / kg) on the body weight of photoperiod-induced Microtus brandti obesity;

[0029] Figure 11This is a graph showing the results of the effect of the BBR-PPD natural medicine combination at different concentrations provided in Example 4 of the present invention on the weight change rate of DIO mice. Detailed implementation mode

[0030] The present invention provides a pharmaceutical composition for preventing and / or treating obesity, fatty liver and hyperglycemia, comprising berberine and 20(S)-protopanaxadiol. The berberine (BBR) of the present invention is mainly derived from plants of the genus Berberis. From the perspective of safety, BBR and PPD have no acute and long-term toxicity, and there is no risk of addiction, no gastrointestinal adverse reactions, and no risk of cardiovascular diseases when the two are used in combination. Their synergistic effect can further enhance the inhibition of food intake in the central nervous system, and at the same time can act on peripheral tissues to promote energy consumption, regulate lipid metabolism, reduce lipid accumulation, improve insulin resistance, lower glucose levels, and the dosage used is within the common dosage range, resulting in a steady decrease in body weight. In a specific embodiment, in the pharmaceutical composition, the mass ratio of berberine to 20(S)-protopanaxadiol is (8-3):1. In a specific embodiment, in the pharmaceutical composition, the mass ratio of berberine to 20(S)-protopanaxadiol is (5-3):1. In a specific embodiment, in the pharmaceutical composition, the mass ratio of berberine to 20(S)-protopanaxadiol is 4:1. In a specific embodiment, the source of the berberine includes chemical synthesis or extraction from plants; the source of the 20(S)-protopanaxadiol includes Panax notoginseng stems and leaves, ginseng stems and leaves or American ginseng stems and leaves. Specifically, the berberine of the present invention can be extracted from plants such as Phellodendron amurense, Phellodendron chinense, Aristolochia fangchi or Berberis vulgaris, or berberine (BBR) can be obtained by chemical synthesis, or it can be a conventional commercially available product, such as purchased from Xi'an Wanfang Biotechnology Co., Ltd. In the present invention, the main source of 20(S)-protopanaxadiol (PPD) is different parts of Panax notoginseng, ginseng, American ginseng, etc., such as roots, stems and leaves. The compound obtained by hydrolysis of these medicinal material parts is 20(S)-protopanaxadiol (PPD). The present invention has no special limitation on the hydrolysis reaction, and a conventional hydrolysis reaction for extracting 20(S)-protopanaxadiol known to those skilled in the art can be used, and it can also be a conventional commercially available 20(S)-protopanaxadiol. In a specific embodiment, the purity of the berberine raw material medicine is 50-100%; the purity of the 20(S)-protopanaxadiol raw material medicine is 50-100%.

[0031] Through pharmacodynamic studies, the anti-obesity mechanisms of BBR and PPD are as follows:

[0032] Anti-obesity mechanism of BBR: (1) In terms of acting on the central nervous system to inhibit feeding, BBR can promote the expression of GLP-1, reduce the levels of serum leptin, ghrelin and NPY, and inhibit feeding; (2) In terms of acting on peripheral tissues to reduce energy intake, BBR can inhibit the expression of lipoprotein lipase, reduce fat synthesis and accumulation, inhibit adipocyte differentiation and proliferation, promote adipose tissue remodeling and thermogenesis, thereby reducing fat content; acting on bitter taste receptors to repair the intestinal barrier; reducing the level of α-glucosidase, as an α-glucosidase inhibitor, it can inhibit the digestion of polysaccharides, oligosaccharides and disaccharides in the intestine during feeding into monosaccharides such as glucose, thus blocking its absorption process; activating the Farnesoid X Receptor (FXR) signaling pathway, reducing bile acid levels, thereby reducing intestinal lipid absorption, and then increasing lipid excretion in feces to achieve the purpose of weight loss; (3) In terms of acting on peripheral tissues to promote energy consumption, activating AMPK, UCP1 / 2, improving insulin resistance, thereby achieving the anti-obesity effect. Anti-obesity mechanism of PPD: (1) In terms of acting on the central nervous system to inhibit feeding, PPD inhibits the expression of NPY in the hypothalamus and increases the expression of CCK to inhibit feeding by improving leptin resistance; (2) In terms of acting on peripheral tissues to promote energy consumption, activating MAPK or SIRT1 to regulate lipid metabolism and reduce lipid accumulation; (3) Acting on peripheral tissues to improve insulin resistance and reduce glucose levels. The combined use of the two can regulate the secretion of leptin by peripheral cells, improve leptin signaling to inhibit the body from feeding, while reducing the level of neuropeptide NPY. Moreover, the combined use of the two can activate AMPK, promote adipose tissue remodeling and thermogenesis, and then reduce lipid accumulation. Both can improve insulin resistance and reduce glucose levels through peripheral tissues. The combined action mechanism of the two has no risk of causing gastrointestinal adverse reactions. Therefore, BBR and PPD are combined for the prevention and / or treatment of obesity, fatty liver and hyperglycemia.

[0033] The present invention also provides a pharmaceutical preparation for the prevention and / or treatment of obesity, fatty liver and hyperglycemia, comprising the pharmaceutical composition described in the above technical solution and a pharmaceutically acceptable carrier or excipient. In a specific embodiment, the type of the pharmaceutical preparation includes an oral preparation. In a specific embodiment, the oral preparation includes capsules, tablets, granules, powders, pills, dripping pills, sustained-release or controlled-release preparations, oral liquids, mixtures or syrups. In a specific embodiment, the excipient includes any one or more of lubricants, fillers, binders and disintegrants.

[0034] The present invention also provides the use of the pharmaceutical composition described in the above technical solution in the preparation of a drug for the prevention and / or treatment of obesity, fatty liver and hyperglycemia.

[0035] To further illustrate the present invention, a pharmaceutical composition, pharmaceutical preparation and application for preventing and / or treating obesity, fatty liver and hyperglycemia provided by the present invention will be described in detail below with reference to the accompanying drawings and embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0036] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the reagents, biological materials, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.

[0037] Test drug:

[0038] 20(S)-Protopanaxadiol (PPD) was prepared in-house. By the method of high-temperature alkali degradation of organic solvents, different purities of 20(S)-protopanaxadiol (PPD) were successively prepared from Panax quinquefolius L. leaves / ginseng leaves / Panax notoginseng leaves by heating with diethylene glycol (high-boiling organic solvent) at 200-240 °C for 2-4 h, and the purities were 50%, 90%, and 99%. (The PPD with different purities and different sources described in each example were all obtained by this method).

[0039] Berberine (BBR) extract was purchased from Xi'an Wanfang Biotechnology Co., Ltd.

[0040] Example 1

[0041] BBR-PPD composition in high-fat diet-induced C57BL / 6 mice

[0042] Animal grouping:

[0043] C57BL / 6 mice, male, 6-8 weeks old. After 7 days of adaptive feeding, they were fed a high-fat diet for 12 weeks to induce the mice into a diet-induced obesity (DIO) model. After feeding C57BL / 6 mice with a high-fat diet for 12 weeks, the body weight of the high-fat diet group was greater than 20% of the average body weight of the normal diet group, as Figure 1 , indicating that the DIO model was successfully constructed.

[0044] C57BL / 6 male mice, 6 - 8 weeks old, after 7 days of adaptive feeding, were randomly divided into 9 groups with 5 mice in each group. They were respectively normal diet control group, high - fat diet group, high - fat diet + BBR (purity 50%) administration group, high - fat diet + BBR (purity 90%) administration group, high - fat diet + BBR (purity 99%) administration group, high - fat diet + PPD (purity 50%) administration group, high - fat diet + PPD (purity 90%) administration group, high - fat diet + PPD (purity 99%) administration group, high - fat diet + BBR - PPD (purities of BBR and PPD in the composition are both 99%) administration group. The normal diet group was fed with normal mouse feed, and the high - fat diet group was fed with high - fat feed (ratio: breeding mouse feed 54.6% + lard 16.9% + sucrose 14% + casein 10.2% + cholesterol 1% + vitamin E 1% + bovine bile salt 0.1% + maltodextrin 2.2%) for 12 weeks. The high - fat feed was purchased from Suzhou Shuangshi Experimental Animal Feed Technology Co., Ltd.

[0045] C57BL / 6 male mice, 6 - 8 weeks old, after 7 days of adaptive feeding, were randomly divided into 7 groups with 5 mice in each group. They were respectively normal diet control group, normal diet + PPD (purity 99%) administration group, normal diet + BBR - PPD (purities are both 99%) administration group; high - fat diet group, high - fat diet + PPD (purity 99%) administration group, high - fat diet + BBR (purity 99%) administration group, high - fat diet + BBR - PPD (purities are both 99%) administration group. The normal diet group was fed with normal mouse feed, and the high - fat diet group was fed with high - fat feed (ratio: breeding mouse feed 54.6% + lard 16.9% + sucrose 14% + casein 10.2% + cholesterol 1% + vitamin E 1% + bovine bile salt 0.1% + maltodextrin 2.2%) for 12 weeks. The high - fat feed was purchased from Suzhou Shuangshi Experimental Animal Feed Technology Co., Ltd.

[0046] Preparation of the administered agents:

[0047] PPD administration group:

[0048] 0.5% sodium carboxymethylcellulose solution was added to 50% PPD powder (extracted from ginseng leaf and stem saponins) to prepare a suspension with a concentration of 8 mg / mL in terms of PPD, stirred evenly, and the administration dose was 100 mg / kg;

[0049] 0.5% sodium carboxymethylcellulose solution was added to 90% PPD powder (extracted from ginseng leaf and stem saponins) to prepare a suspension with a concentration of 8 mg / mL in terms of PPD, stirred evenly, and the administration dose was 100 mg / kg;

[0050] Add 0.5% sodium carboxymethylcellulose solution to 99% PPD powder (extracted from ginseng stem and leaf saponins) to prepare a suspension with a concentration of 8 mg / mL based on PPD. Stir well and the dosing dose is 100 mg / kg.

[0051] BBR dosing group:

[0052] Add 0.5% sodium carboxymethylcellulose solution to 50% BBR powder, heat in boiling water, stir well, and the dosing dose is 400 mg / kg;

[0053] Add 0.5% sodium carboxymethylcellulose solution to 90% BBR powder, heat in boiling water, stir well, and the dosing dose is 400 mg / kg;

[0054] Add 0.5% sodium carboxymethylcellulose solution to 99% BBR powder, heat in boiling water, stir well, and the dosing dose is 400 mg / kg.

[0055] BBR-PPD composition dosing group: Prepare the medicament by the above method, and the dosing dose is 100 mg / kg of PPD and 400 mg / kg of BBR (the purities of BBR and PPD in the composition are both 99%).

[0056] After successful modeling, the normal diet + PPD (NF + PPD) dosing group (purity 99%), normal diet + BBR-PPD composition (NF + BBR-PPD) dosing group (purities are both 99%), high-fat diet + PPD (HF + PPD) dosing group (purity 99%), high-fat diet + BBR (HF + BBR) dosing group (purity 99%), and high-fat diet + BBR-PPD composition (HF + BBR-PPD) dosing group (purities are both 99%) are given intragastric administration once a day, and the medicament is shaken well before use. The normal control (NF) group and the high-fat diet (HF) group are given an equal amount of clear water by intragastric administration every day. The normal group is fed with ordinary feed every day, and the high-fat model group is fed with high-fat feed. The administration is continued for 4 weeks. During the experiment, the mice are allowed to eat and drink freely, and the body weight, food intake, glycolipid metabolism, and related indicators of the degree of body fat accumulation of the mice are monitored every day.

[0057] 1. Changes in the body weight of DIO mice after drug intervention at different drug purities.

[0058] During the experiment, observe the mental state, hair, and whether diarrhea symptoms occur in the mice every day.

[0059] During the experiment, monitor the body weight and food intake of the mice every day, and calculate the body weight change rate of the mice in each experimental group by the method of self-control according to the following formula on the last day after dosing.

[0060]

[0061] In the formula, W 2 is the body weight of the mice in each group on the last day of drug administration, and W 1 is the body weight of the mice in each group on the day before model establishment.

[0062] Table 1 Body weight change rates of PPD, BBR, and BBR-PPD groups with different purities

[0063] Group Weight change rate (%) Compared with HF group (p value) Intra-group purity difference (p value) NF group 105.2±1.5 —— —— HF group 135.8±2.1 —— —— HF + PPD (50%) 128.4±3.0 0.021* —— HF + PPD (90%) 122.1±2.7 <0.001** 0.048* vs 50% PPD HF + PPD (99%) 118.5±2.3 <0.001** 0.012* vs 90% PPD HF + BBR (50%) 126.8±2.9 0.038* —— HF + BBR (90%) 119.6±2.5 <0.001** 0.025* vs 50% BBR HF + BBR (99%) 115.4±1.6 <0.001** 0.015* vs 90% BBR HF + BBR - PPD 112.3±1.8 <0.001** 0.006* vs 99% single drug

[0064] During the experiment, the mental state of the mice in each group was good, the hair was fluffy and shiny. As shown in Table 1, high-purity PPD (99%) significantly inhibited the body weight gain of HF mice (body weight change rate: 118.5% vs 135.8% in the HF group, p < 0.001), and the effect was better than that of low-purity PPD (99% vs 90% PPD group, p = 0.012). Similarly, the weight loss effect of high-purity BBR (99%) was significantly stronger than that of the low-purity group (p = 0.015). It is worth noting that the BBR-PPD composition (99% purity) showed a synergistic effect, and the body weight change rate (112.3%) was significantly lower than that of the single high-purity drug group (p = 0.006), indicating that the increased purity can enhance the combined efficacy.

[0065] Low-purity drugs (such as 50% and 90%) may reduce the bioavailability of the active ingredient and interfere with target binding due to the presence of impurities, while 99%-purity drugs can maximize the drug effect and achieve synergy. Therefore, only 99%-purity drugs were selected in the subsequent experiments to ensure the reliability of the results.

[0066] Note: Considering that the NF group did not receive a high-fat diet, different purities of PPD and BBR did not show obvious significant differences in it. Therefore, in the experiment, it was mainly used as a control group, and the effect of different purities of PPD and BBR in the group on the body weight change rate of mice was not investigated.

[0067] 2. Basic conditions of DIO mice and changes in body weight and food intake of mice after drug intervention

[0068] During the experiment, the mental state, hair, and whether diarrhea symptoms occurred in the mice were observed daily.

[0069] During the experiment, the body weight and food intake of the mice were monitored daily, and after the last day of drug administration, the body weight change rate of the mice in each experimental group was calculated by the method of self-control according to the following formula.

[0070]

[0071] In the formula, W 2 is the body weight of the mice in each group on the last day of drug administration, and W 1It is the body weight of the mice in each group one day before modeling.

[0072] During the experiment, the mental state of the mice in each group was good, their hair was fluffy and shiny. After administration, diarrhea was not induced in the mice in each experimental group. As Figure 2 and Figure 3 shown, after administration, the food intake of the mice on normal diet did not change significantly compared with that of the normal control group, and the average body weight growth rate was slower, but the difference was not significant. After administration, the average body weight change rate of DIO mice decreased significantly ([In Figure 2 , a positive body weight change rate indicates an increase in the body weight of the mice, and a negative body weight change rate indicates a decrease in the body weight of the mice), and the food intake showed a significant decreasing trend compared with that of the HF group. Therefore, after drug intervention, the appetite of the mice can be effectively inhibited, and by reducing the active food intake of DIO mice, the effect of weight loss can be achieved, and the effect of the BBR-PPD composition in inhibiting appetite and controlling body weight is significantly better than that of PPD and BBR alone.

[0073] 3. Glucose and lipid metabolism in DIO mice after drug intervention

[0074] (1) Determination of fasting blood glucose (FBG) in DIO mice

[0075] After the mice in each group were given the corresponding drugs, the fasting blood glucose (FBG) of the mice in each group was measured. On the day of gavage and the last day after the end of drug administration, after fasting but not water deprivation for 12 h, blood was collected from the tail vein, and the fasting blood glucose (FBG) of the mice in each group was detected with a blood glucose meter.

[0076] (2) Collection method of serum samples from DIO mice

[0077] On the last day after the end of drug administration to the mice in each group, after fasting but not water deprivation for 12 h, the mice were anesthetized with ether, and peripheral blood was collected by enucleating the eyeballs. After being placed at room temperature for 2 h, it was centrifuged at 3000 rpm / min for 15 min at 4°C, and the upper-layer serum was collected. After repeating the centrifugation operation once, the upper-layer serum was continuously aspirated and stored at -80°C for later measurement.

[0078] (3) Determination of blood lipid levels and liver function in DIO mice

[0079] After thawing the serum samples, they were centrifuged again to obtain the supernatant. The four blood lipid levels and liver function biochemical indexes of the mice were detected with an automatic biochemical analyzer. The required matching reagent kits were placed in the analyzer, and the corresponding parameters were set for automatic determination. The four blood lipid levels include triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C).

[0080] (4) Results

[0081] Fasting blood glucose (FBG): After each dosing cycle, the blood glucose of mice was measured, and it was found that the fasting blood glucose value of the mice in the model group was much higher than that in the normal diet group (P < 0.001). As Figure 4 shown, compared with the HF group, the FBG values of the PPD group and the BBR-PPD composition-administered group decreased, and there were significant differences (P < 0.05). Although the FBG value of the BBR-administered group showed a downward trend, there was no obvious difference. Although the FBG value of the normal diet-administered group showed a downward trend compared with the normal control group, there was no obvious difference.

[0082] The abnormal lipid metabolism caused by obesity is usually manifested as an increase in the levels of TG, CHO, and LDL-C, and a decrease in the level of HDL-C.

[0083] Triglyceride (TG) and total cholesterol (CHO): Under the induction of a high-fat diet, the levels of TG and CHO in the model group of mice were significantly increased compared with those in the normal diet-fed mice (P < 0.001, P < 0.0001), while after administration to DIO mice, the levels of TG and CHO were significantly decreased compared with the model group. The order of the effects of the administered groups on the levels of TG and CHO in DIO mice was: BBR-PPD composition-administered group > BBR-administered group > PPD-administered group. Compared with the normal diet control group, after administration with the BBR-PPD composition, there was a significant difference in the TG level (P < 0.05), but although the CHO level decreased, there was no statistical difference between groups.

[0084] High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C): Under the induction of a high-fat diet, the levels of HDL-C and LDL-C in the serum of the model group of mice were significantly increased compared with those in the normal diet group of mice, and there were significant differences (P < 0.01, P < 0.0001). After administration to DIO mice, compared with the model group, the content of HDL-C in the serum increased significantly, while the content of LDL-C decreased significantly. It should be noted that compared with the normal diet group, the content of HDL-C in the normal diet-administered group also increased (P < 0.05, P < 0.01), and the content of LDL-C also decreased (P < 0.05, P < 0.01).

[0085] As Figure 5 shown, the above detection results of blood lipid levels indicate that after drug intervention, it can improve the serum parameter levels, regulate the lipid metabolism of mice, and has the effect of reducing blood lipids, and the effect of the BBR-PPD composition is better than that of PPD and BBR alone. 。

[0086] 4. Degree of body fat accumulation in DIO mice after drug intervention

[0087] (1) Collection of fat samples

[0088] After blood collection, excise the epididymal fat, perirenal fat, and peritoneal fat of the mice.

[0089] (2) Determination of fat storage in adipose tissue and visceral fat index in DIO mice

[0090] After collecting the epididymal fat, perirenal fat, and peritoneal fat of the mice, wipe off the blood stains with gauze and immediately weigh them to record the fat storage of each group of mice. And calculate the visceral fat index of each group of mice according to the following formula.

[0091]

[0092] (3) Results

[0093] The results showed that compared with the normal group, there were significant differences in the visceral fat index in the HF group (P < 0.001, P < 0.0001), and the visceral fat content in the HF model group was significantly higher than that in the normal group; compared with the HF group, the contents of epididymal fat, perirenal fat, and peritoneal fat in each drug administration group decreased. The change order was: BBR-PPD administration group > PPD administration group > BBR administration group. It indicated that after drug intervention, the accumulation degree of visceral fat in obese mice was significantly improved. Compared with the normal control group and the normal diet drug administration group, although there was a tendency for the epididymal fat and perirenal fat indices to decrease, there was no statistical difference. However, the peritoneal fat index decreased by 53.47% and 53.13% respectively in the PPD and BBR-PPD combination administration groups compared with the control group, and there was a significant difference (P < 0.05). It may be because a certain amount of fat can serve as a protective layer for internal organs in the body, so the degree of fat accumulation in the body was reduced to some extent, but the change was not significant. The above experimental results showed (as Figure 6 、 Figure 7 and Figure 8 shown), after drug intervention, it could significantly reduce the degree of fat accumulation in DIO mice, with the effects of weight loss and lipid reduction, and the effect of the BBR-PPD combination was better than that of PPD and BBR alone.

[0094] Example 2

[0095] Induction of fatty liver in SD rats by BBR-PPD combination under high-fat diet

[0096] Animal grouping:

[0097] SD rats, male, 6 - 8 weeks old. After 7 days of adaptive feeding, they were randomly divided into 7 groups with 5 rats in each group, namely the normal diet control group, the normal diet + PPD administration group, the normal diet + BBR - PPD administration group; the high - fat diet group, the high - fat diet + PPD administration group, the high - fat diet + BBR administration group, and the high - fat diet + BBR - PPD administration group. The normal diet group was fed with ordinary feed for SD rats, and the high - fat diet group was fed with high - fat feed (ratio: breeding rat feed 54.6% + lard 16.9% + sucrose 14% + casein 10.2% + premix 2.1% + maltodextrin 2.2%) for 12 weeks of induction.

[0098] Configuration of the administered drugs:

[0099] PPD administration group: PPD powder (extracted from Panax quinquefolium L. stem and leaf, purity 99%) was added with 0.5% sodium carboxymethylcellulose solution to prepare a suspension with a concentration of 8 mg / mL in terms of PPD. After stirring evenly, the administration dose was 100 mg / kg;

[0100] BBR administration group: BBR powder (purity 99%) was added with 0.5% sodium carboxymethylcellulose solution, heated in boiling water, and stirred evenly. The administration dose was 400 mg / kg;

[0101] BBR - PPD combination administration group: The drug was configured by the above method, and the administration dose was PPD 100 mg / kg and BBR 400 mg / kg (the purity of BBR and PPD in the combination was 99% each).

[0102] After successful modeling, the normal diet + PPD (NF + PPD) administration group, the normal diet + BBR - PPD combination (NF + BBR - PPD) administration group, the high - fat diet + PPD (HF + PPD) administration group, the high - fat diet + BBR (HF + BBR) administration group, and the high - fat diet + BBR - PPD combination (HF + BBR - PPD) administration group were given intragastric administration once a day. The administered drugs were shaken evenly before use. The normal control (NF) group and the high - fat diet (HF) group were given an equal amount of clear water by intragastric administration every day. The normal group was fed with ordinary feed every day, and the high - fat model group was fed with high - fat feed. The administration continued for 4 weeks. During the experiment, the rats were allowed to eat and drink freely, and the body weight and food intake of the rats were monitored daily.

[0103] 1. Body weight

[0104] During the experiment, the body weight and food intake of the rats were monitored daily. After the last day of administration, the weight change rate of the rats in each experimental group was calculated by the method of self - control according to the following formula.

[0105]

[0106] In the formula, W 2 is the body weight of the rats in each group on the last day of drug administration, and W 1 is the body weight of the rats in each group on the day before model establishment.

[0107] During the experiment, the mental state of the rats in each group was good, the hair was fluffy and shiny. After drug administration, diarrhea was not induced in the rats of each experimental group. As Figure 9 shown, after drug intervention, it can effectively inhibit the appetite of rats, reduce the active food intake of rats, achieve the effect of weight loss, and compared with the normal diet control group and the high-fat model group, the BBR-PPD composition is superior to PPD and BBR alone in inhibiting appetite and controlling body weight.

[0108] 2. Collection of observation specimens

[0109] 36 h before the end of the experiment, the rats were individually housed in a metabolic cage, allowed free access to water, normally fed, and the corresponding feed was 20 g / rat / day. The feces of each animal within 24 h were collected. After collecting the feces, the animals were transferred back to the previous ordinary animal cage from the metabolic cage for continued feeding. At the same time, 12 h before the end of the experiment, all animals were fasted, allowed free access to water, and after fasting for 11 h, they were given the last dose according to the established protocol. After 1 h of drug administration, they were anesthetized with ether, blood was taken from the medial canthus vein of the orbit, and after being anesthetized with ether, they were sacrificed by dislocation of the cervical vertebrae. The liver and small intestine of the rats were separated by laparotomy, washed clean with pre-cooled PBS at 4°C and then directly processed, or stored at -80°C for later use.

[0110] After the whole blood coagulated for 2 h, it was centrifuged at 3000 rpm for 15 min in a centrifuge, and the serum was taken for direct detection or stored at -80°C for later use.

[0111] 3. Liver index

[0112] Calculate the wet liver weight / body weight × 100%, which is the liver index.

[0113] Table 2 Body weight, liver weight and liver weight index of rats in each group

[0114] Group n Body weight (g) Liver weight (g) Liver index (%) NF 8 258.3±12.1 5.2±0.4 2.01±0.15 NF + PPD 8 252.6±10.8 5.1±0.3 2.02±0.12 NF + PPD - BBR 8 255.9±11.5* 5.3±0.3* 2.07±0.13* HF 8 332.7±18.5 12.6±1.1 3.79±0.28 HF + PPD 8 318.4±16.2# 10.8±0.9## 3.39±0.24## HF + BBR 8 308.5±15.7## 9.5±0.8## 3.08±0.21## HF + PPD - BBR 8 295.2±14.3## 8.1±0.7## 2.75±0.18##

[0115] Note: Compared with the normal group (NF group), * indicates P < 0.05; compared with the model group (HF group), # indicates P < 0.05, and ## indicates P < 0.01.

[0116] The results of the body weight, liver weight and liver weight index of rats in each group are shown in Table 2. Conclusion: Compared with the normal diet group, the body weight of the rats in the high-fat diet group increased faster. The body weight growth rate of each drug administration group slowed down after the second week of drug administration, slower than that of the model group. As shown in Table 2, compared with the rats in the high-fat diet group, the liver index of the drug administration group showed a decreasing trend, but the rats in the BBR-PPD composition group had the best recovery of liver index among the drug groups.

[0117] 4. Serum index determination

[0118] Automatically detect serum biochemical analysis indicators.

[0119] Determine according to the method provided by the kit: use cholesterol oxidase-PAP method to determine serum TC content, glycerol phosphate oxidase-PAP method to determine serum TG content, and phosphotungstic acid magnesium (PTA-Mg++) precipitation method to determine serum HDL-C and LDL-C. Use the Reitman method to determine ALT content and colorimetry to determine serum AST.

[0120] The conclusions are as follows in Table 3:

[0121] (1) Changes in serum TG: Compared with the normal diet group, the serum TG level in the high-fat diet group increased, with statistical significance (P<0.05). The model group showed the characteristics of hypertriglyceridemia. All drug administration groups significantly improved serum TG (P<0.05), and among them, the BBR-PPD group had a better lipid-lowering effect compared with the PPD group and the BBR group.

[0122] (2) Changes in serum TC: Compared with the normal diet group, the mean serum total cholesterol level in the high-fat diet group increased, but there was no statistical significance. Compared with the model group, none of the drug administration groups decreased; the BBR-PPD group, the BBR group, and the PPD group all increased TC. This indicates that the model induced by this high-fat diet did not show the characteristics of hypercholesterolemia and the impact of each drug administration group on serum TC was small, with a certain inhibitory effect on growth.

[0123] (3) Changes in serum LDL: Compared with the normal diet group, there was no statistical difference in serum LDL in the high-fat diet group. Compared with the high-fat model group, none of the drug administration groups showed an effect of lowering LDL, and even the BBR-PPD group, the BBR group, and the PPD group all increased LDL. This indicates that none of the drug administration groups had an inhibitory effect on the model induced by high-fat diet for LDL.

[0124] (4) Changes in serum HDL: Compared with the normal diet group, there was no statistically significant increase in serum HDL level in the high-fat diet group. Compared with the high-fat model group, the BBR-PPD group, the PPD group, and the BBR group all increased HDL.

[0125] (5) Changes in ALT content: Compared with the normal diet group, ALT in the high-fat diet group was significantly higher than that in the normal control group. Among the drug administration groups, ALT in the HF+PPD and HF+BBR groups decreased significantly, but the values were still higher than the normal range, and ALT in the HF+PPD-BBR group was significantly lower than that in the normal control group.

[0126] (6) Changes in AST content: Compared with the normal diet group, AST was significantly increased in the high-fat diet group. In each administration group, ALT was partially improved in the HF+PPD and HF+BBR groups, but the values were still higher than the normal range. ALT in the HF+PPD-BBR group was significantly lower than that in the normal control group, and the effect was significantly better than that of the single drug group.

[0127] Table 3 Data of each index

[0128]

[0129] Note: Compared with the normal group, * indicates P<0.05.

[0130] Conclusion:

[0131] Compared with the normal diet group, the liver TG level in the high-fat diet group was significantly increased, with a statistically significant difference (P<0.05). The high-fat model group showed typical characteristics of fatty liver, and the liver fat content was about twice that of the normal group. Compared with the model group, the effect of improving liver TG in each administration group was significant, and the liver TG level was significantly improved (P<0.05). This suggests that the BBR group, PPD group, and BBR-PPD group all have the effect of treating fatty liver and improving the accumulation of liver fat, but the effect of the BBR-PPD group is the best.

[0132] 5. Results

[0133] The combination of the BBR-PPD natural product composition can effectively improve the in vivo metabolic level, and then improve the accumulation of liver fat. Therefore, the BBR-PPD composition has excellent effects in preventing and / or treating obesity and reducing blood sugar and blood lipids.

[0134] Example 3

[0135] BBR-PPD composition photoperiod-induced obesity model in Brandt's voles

[0136] Grouping of experimental animals:

[0137] Male Brandt's voles (n = 24) were caged under a long-day (16L:8D, LD) photoperiod from birth. These voles were transferred to short-day (8L:16D, SD) conditions when they were 35 days old and kept there for 70 days. Voles do not reproduce under short-day conditions, so it is impossible to rear animals under SD conditions from birth. Fourteen days after acclimation to SD, temperature and activity transmitters were implanted intraperitoneally in 16 voles. After 70 days of SD domestication, they were randomly divided into two groups. The animals were randomized using random numbers. After randomization, there was no significant difference in body weight between the groups. One group (n = 12) was kept under SD conditions for another 70 days, while the other group (n = 12) was transferred to the LD photoperiod for 70 days. Exposure to the LD photoperiod led to a gradual increase in body weight, indicating successful establishment of an obesity model. Body weight and food intake were measured daily. The researchers stated that the voles were not oblivious to the photoperiod treatment because it was impossible to disguise which room was long-day and which was short-day.

[0138] The SD group and the LD group were each divided into 4 groups, with 3 animals in each group, namely the short-day group (SD group), the short-day + PPD administration group (SD + PPD group), the short-day + BBR administration group (SD + BBR group), and the short-day + BBR-PPD administration group (SD + BBR-PPD group); the long-day group (LD group), the long-day + PPD administration group (LD + PPD group), the long-day + BBR administration group (LD + BBR group), and the long-day + BBR-PPD administration group (LD + BBR-PPD group). The SD group and the LD group were provided with weighed dry food.

[0139] Configuration of the administered drugs:

[0140] PPD administration group: PPD powder (extracted from ginsenosides of Panax ginseng C. A. Mey. stems and leaves, purity 99%) was added to a 0.5% sodium carboxymethylcellulose solution to prepare a suspension with a concentration of 8 mg / mL in terms of PPD. After stirring evenly, the administration dose was 100 mg / kg;

[0141] BBR administration group: BBR powder (purity 99%) was added to a 0.5% sodium carboxymethylcellulose solution, heated in boiling water, and stirred evenly. The administration dose was 400 mg / kg;

[0142] BBR-PPD combination administration group: The drug was configured by the above method, and the administration dose was 100 mg / kg of PPD and 400 mg / kg of BBR (the purities of BBR and PPD in the combination were both 99%).

[0143] After successful modeling, the short-day group, short-day + PPD administration group, short-day + BBR administration group, short-day + BBR-PPD administration group; long-day group, long-day + PPD administration group, long-day + BBR administration group, and long-day + BBR-PPD administration group were fed quantitatively, administered once a day, and the administered drugs were shaken well before use. The short-day (SD) group and the long-day (LD) group were fed an equal amount of clear water every day. All eight groups were fed with weighed dry food and administered drugs continuously for 4 weeks. During the experiment, the voles were allowed to eat and drink freely, and their body weights and food intakes were monitored daily.

[0144] 1. Body weight

[0145] During the experiment, the body weights of the voles were monitored daily, and after the last day of drug administration, the weight change rates of the rats in each experimental group were calculated by the method of self-control according to the following formula.

[0146]

[0147] In the formula, W 2 is the body weight of the voles in each group on the last day of drug administration, and W 1 is the body weight of the voles in each group on the day before modeling.

[0148] During the experiment, the voles in each group had normal diets and good mental states. After drug administration, no deaths occurred in the voles in each experimental group. As Figure 10 shown, after drug intervention, the appetite of the voles can be effectively inhibited, the active food intake of the voles can be reduced, and the weight loss effect can be achieved. Moreover, the BBR-PPD composition has better effects on inhibiting appetite and controlling body weight than PPD and BBR alone.

[0149] 2. Results

[0150] The combination of the BBR-PPD natural product composition can effectively improve the in vivo metabolic level, and then improve the accumulation of liver fat. Therefore, the BBR-PPD composition has excellent effects on preventing and / or treating obesity and reducing blood sugar and blood lipids. Moreover, in different purity cases, the effects of the BBR-PPD composition are better than those of the normal diet control group, PPD alone, and BBR alone.

[0151] Example 4

[0152] C57BL / 6 mice induced by high-fat diet with different concentrations of BBR-PPD composition

[0153] Grouping of experimental animals:

[0154] C57BL / 6 male mice, 6 - 8 weeks old, after 7 days of adaptive feeding, were fed a high - fat diet for 12 weeks to induce them into a diet - induced obesity (DIO) model. After 12 weeks of feeding C57BL / 6 mice with a high - fat diet, the body weight of the high - fat diet group was more than 20% greater than the average body weight of the normal diet group, indicating successful construction of the DIO model.

[0155] C57BL / 6 male mice, 6 - 8 weeks old, after 7 days of adaptive feeding, were randomly divided into 7 groups with 5 mice in each group. They were respectively the normal diet control group, the normal diet + BBR - PPD (ratio 3:1) administration group, the normal diet + BBR - PPD (ratio 4:1), the normal diet + BBR - PPD (ratio 3:2); the high - fat diet group, the high - fat diet + BBR - PPD (ratio 3:1) administration group, the high - fat diet + BBR - PPD (ratio 4:1) administration group, the high - fat diet + BBR - PPD (ratio 3:2) administration group. The normal diet group was fed with ordinary feed, and the high - fat diet group was fed with a high - fat diet (formulation: breeding mouse feed 54.6% + lard 16.9% + sucrose 14% + casein 10.2% + premix 2.1% + maltodextrin 2.2%) for 12 weeks of induction.

[0156] Configuration of the administered drugs:

[0157] PPD administration group:

[0158] PPD powder (extracted from ginseng leaf and stem saponins, purity 99%) was added to a 0.5% sodium carboxymethylcellulose solution to prepare a suspension with a concentration of 8 mg / mL in terms of PPD, stirred evenly, and the administration doses were 100 mg / kg and 200 mg / kg;

[0159] BBR administration group:

[0160] BBR powder (purity 99%) was added to a 0.5% sodium carboxymethylcellulose solution, heated in boiling water, stirred evenly, and the administration doses were 400 mg / kg and 300 mg / kg;

[0161] BBR - PPD combination administration group: The drugs were configured by the above - mentioned method, and the administration doses were PPD 100 mg / kg, 200 mg / kg, BBR 400 mg / kg, 300 mg / kg, and were formulated according to the ratios described in each group (the purities of PPD and BBR in the combination were both 99%).

[0162] After successful modeling, the normal diet + BBR-PPD composition (ratio 3:1) administration group, normal diet + BBR-PPD composition (ratio 3:2) administration group, normal diet + BBR-PPD composition (ratio 4:1), high-fat diet + BBR-PPD composition (ratio 3:1) administration group, high-fat diet + BBR-PPD composition (ratio 3:2) administration group, and high-fat diet + BBR-PPD composition (ratio 4:1) administration group were given gavage administration once a day. The administered medicine was shaken well before use. The normal control (NF) group and the high-fat diet (HF) group were given an equal amount of clear water by gavage every day. The normal group was fed with normal feed every day, and the high-fat model group was fed with high-fat feed. The administration continued for 4 weeks. During the experiment, the mice were allowed to eat and drink freely, and their body weights and food intakes were monitored daily.

[0163] 1. Basic conditions of DIO mice and changes in body weights of mice after drug intervention

[0164] During the experiment, the mental state, hair, and whether diarrhea symptoms occurred were observed in the mice every day.

[0165] During the experiment, the body weights and food intakes of the mice were monitored daily. After the last day of administration, the body weight change rates of the mice in each experimental group were calculated by the method of self-control according to the following formula.

[0166]

[0167] In the formula, W 2 is the body weight of the mice in each group on the last day of administration, and W 1 is the body weight of the mice in each group on the day before modeling.

[0168] During the experiment, the mental states of the mice in each group were good, their hair was fluffy and shiny. After administration, diarrhea was not caused in the mice in each experimental group. As Figure 11 is known, after drug intervention, the appetite of the mice can be effectively inhibited, and the body weight can be reduced by reducing the active food intake of DIO mice. Moreover, the BBR-PPD composition (ratio 4:1) has a better effect on suppressing appetite and controlling body weight than the other two ratios of BBR-PPD compositions.

[0169] Example 5

[0170] Granules

[0171] Take a total of 100 g of 20(S)-PPD and BBR, where the mass ratio of 20(S)-PPD to BBR is 1:4. Add 1.5 times the amount of dextrin, 0.5% sucrose, and 1.5% microcrystalline cellulose respectively, and dissolve them with an appropriate amount of ethanol to make a soft material (soft material state: it can be formed into a ball when held and dispersed when lightly pressed), granulate, and dry in a blast dryer at 60 °C.

[0172] Example 6

[0173] Drop pills

[0174] Take a total of 100 g of 20(S)-PPD and BBR, where the mass ratio of 20(S)-PPD to BBR is 1:4. Add 1000 g of polyethylene glycol, mix evenly, melt, and use a drop pill machine to make drop pills.

[0175] Example 7

[0176] Suspension

[0177] Take a total of 100 g of 20(S)-PPD and BBR, where the mass ratio of 20(S)-PPD to BBR is 1:4. Add 0.5% CMC-Na to prepare a suspension.

[0178] Example 8

[0179] Oral liquid

[0180] Take a total of 2 g of 20(S)-PPD and BBR, where the mass ratio of 20(S)-PPD to BBR is 1:4. Mix with 48 mL of syrup and dissolve in 100 ml of pure water, homogenize, filter, sterilize instantaneously at high temperature (135 °C, 4 s), and fill aseptically and sub-pack. An oral liquid is prepared.

[0181] The component amounts within the above examples and the scope of the specification can be enlarged or reduced proportionally according to production needs.

[0182] Experimental studies have shown that the composition of the present invention has significant effects on reducing lipid levels and improving glucose and lipid metabolism. Compared with single use, advantageous effects can be obtained, and it has good curative effects in the treatment / prevention of obesity, fatty liver, and hyperglycemia.

[0183] Although the above examples have described the present invention in detail, they are only a part of the embodiments of the present invention, not all embodiments. People can also obtain other embodiments based on these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A pharmaceutical composition for preventing and / or treating obesity, fatty liver and hyperglycemia, characterized in that: Includes berberine and 20(S)-protopanaxadiol.

2. The pharmaceutical composition according to claim 1, characterized in that In the pharmaceutical composition, the mass ratio of berberine to 20(S)-protopanaxadiol is (8-3):

1.

3. The pharmaceutical composition according to claim 2, characterized in that In the pharmaceutical composition, the mass ratio of berberine to 20(S)-protopanaxadiol is (5-3):

1.

4. The pharmaceutical composition according to any one of claims 1 to 3, characterized in that The sources of the berberine include chemical synthesis or extraction from plants; the sources of the 20(S)-protopanaxadiol include stems and leaves of Panax notoginseng, stems and leaves of Panax ginseng or stems and leaves of American ginseng.

5. The pharmaceutical composition according to any one of claims 1 to 3, characterized in that The purity of the raw material medicine of berberine is 50-100%; the purity of the raw material medicine of 20(S)-protopanaxadiol is 50-100%.

6. A pharmaceutical preparation for preventing and / or treating obesity, fatty liver and hyperglycemia, characterized in that: The invention comprises the pharmaceutical composition according to any one of claims 1 to 5 and a pharmaceutically acceptable carrier or excipient.

7. The pharmaceutical preparation according to claim 6, characterized in that The types of the pharmaceutical preparations include oral preparations; the oral preparations include capsules, tablets, granules, powders, pills, drop pills, sustained-release preparations, oral liquids, mixtures or syrups.

8. The pharmaceutical preparation according to claim 6, characterized in that The auxiliary materials include any one or more of lubricants, fillers, binders and disintegrants.

9. Use of the pharmaceutical composition according to any one of claims 1 to 5 in the preparation of a drug for preventing and / or treating obesity, fatty liver and hyperglycemia.

10. Use of the pharmaceutical composition according to any one of claims 1 to 5 in the preparation of products for suppressing appetite, reducing body weight, lowering blood lipids or blood sugar.

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