Othanol acetate, derivatives thereof and application of othanol in preparation of drugs or food for improving lipid metabolism

Abstract

The invention discloses an application of ingenol acetate, derivatives thereof and ingenol in preparation of drugs or foods for improving lipid metabolism, and relates to the technical field of biological medicines. The invention discloses application of incarviol acetate, incarviol or pharmaceutically acceptable salts or esters of the incarviol acetate and the incarviol in preparation of drugs for preventing, improving and / or treating diseases or symptoms related to lipid metabolism disorder or food or functional health care products for non-disease symptoms. Experiments show that the amenol acetate and the amenol have remarkable effects of improving lipid metabolism and reducing weight. The weight of a model animal can be effectively reduced, the fat tissue mass is reduced, the liver lipid accumulation can be remarkably reduced, and the overall lipid metabolism condition is improved.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to inulin acetate and its derivatives, and the application of inulin in the preparation of drugs or foods that improve lipid metabolism. Background Technology

[0002] Lipid metabolism disorders are often accompanied by multiple complications, significantly reducing patients' quality of life. However, due to the complexity of the disease mechanisms, developing ideal drugs that significantly improve lipid metabolism and weight loss while maintaining good safety profiles presents a significant challenge. Meanwhile, the global prevalence of metabolic diseases and the surge in the affected population further highlight the urgent need for novel treatment strategies. The rich knowledge and experience inherent in traditional medicine provide important clues and insights for discovering potential therapeutic drugs with low toxicity and high efficacy.

[0003] Tracing the history of drug development, natural products and their derived ethnic pharmacological experiences are important sources of new drugs. A noteworthy phenomenon is that drugs derived from their natural prototypes often exhibit enduring vitality (e.g., artemisinin, paclitaxel), while highly purified or modified monomeric chemical drugs, although more potent, are often accompanied by significant toxic side effects and face the risk of being phased out due to insufficient safety or efficacy. This has prompted the research community to re-emphasize the search for new drug clues from natural products. In traditional Chinese medicine theory, herbs with "blood-activating" effects (e.g., Panax notoginseng, Salvia miltiorrhiza) are believed to have lipid-regulating and fatty liver-improving effects, providing important insights and directions for exploring naturally derived lipid-regulating and weight-loss active substances. In particular, resinous Chinese medicines, as a class of special metabolites produced by plants in response to stress, include many varieties (e.g., frankincense, myrrh, dragon's blood) classified as blood-activating and stasis-removing drugs. Their unique chemical component systems have the potential for in-depth research to discover novel active molecules that regulate lipid metabolism. Summary of the Invention

[0004] Given the side effects and limited applicability of existing lipid-regulating and weight-loss drugs, this invention aims to screen safe and effective novel active ingredients from natural products to develop therapeutic strategies for improving lipid metabolism disorders. Furthermore, this invention provides inulin acetate and its derivatives, and the application of inulin in the preparation of drugs or foods that improve lipid metabolism.

[0005] The technical solution of the present invention is as follows:

[0006] In a first aspect, the present invention provides the use of inulin acetate represented by formula (I), inulin represented by formula (II), or a pharmaceutically acceptable salt or ester of both, in the preparation of a medicament for the prevention, improvement, and / or treatment of diseases or conditions associated with lipid metabolism disorders.

[0007]

[0008] Secondly, the present invention provides the use of inulin acetate represented by formula (I), inulin represented by formula (II), or a pharmaceutically acceptable salt or ester of both, in the preparation of food or functional health products for the prevention, improvement and / or treatment of non-disease symptoms associated with lipid metabolism disorders.

[0009]

[0010] Furthermore, the diseases or conditions associated with lipid metabolism disorders are selected from one or more of the following: obesity, metabolic-associated fatty liver disease, diabetes, and atherosclerosis.

[0011] Furthermore, the non-disease symptoms associated with lipid metabolism disorders are selected from one or more of the following: obesity, liver damage, abnormal blood glucose levels, and abnormal blood lipid levels.

[0012] Furthermore, the drug is an injection, tablet, powder, granule, pill, capsule, oral liquid, ointment, cream, nano-formulation, or spray.

[0013] Furthermore, the food or functional health product is an oral liquid, tea, lozenge, capsule, beverage, effervescent tablet or chewable tablet.

[0014] Furthermore, the inermine acetate and / or inermine are in the form of a pharmaceutical composition or a functional health food composition, wherein the pharmaceutical composition comprises the inermine acetate and / or inermine, or a pharmaceutically acceptable salt or ester of both, and one or more pharmaceutically acceptable excipients; and the functional health food composition comprises the inermine acetate and / or inermine, or a pharmaceutically acceptable salt or ester of both, and one or more food-acceptable excipients.

[0015] Thirdly, the present invention provides a pharmaceutical composition comprising the inulin acetate and / or inulin, or a pharmaceutically acceptable salt or ester of both, and one or more pharmaceutically acceptable excipients.

[0016] Fourthly, the present invention provides a functional health food composition comprising the inulin acetate and / or inulin, or a pharmaceutically acceptable salt or ester of both, and one or more food-acceptable excipients.

[0017] This invention utilizes a targeted screening strategy based on traditional medical theory, focusing on the medicinal resources of dried frankincense resin. Inermentol acetate is one of the main components of frankincense resin. Pharmacodynamic evaluation in animal models (such as a high-fat diet-induced obese mouse model) has demonstrated that inermentol acetate significantly improves lipid metabolism and promotes weight loss. It not only effectively reduces the body weight and adipose tissue mass in model animals but also significantly reduces hepatic lipid accumulation and improves overall lipid metabolism. More importantly, it simultaneously enhances insulin sensitivity in the models, indicating its comprehensive benefits in regulating glucose and lipid metabolism.

[0018] Further mechanistic studies have shown that the beneficial effects of inermol acetate are related to its regulation of specific metabolic pathways (such as hepatic nuclear receptors) and its influence on the gut microbiota. Preliminary safety assessments showed no significant adverse reactions in subacute or chronic-like toxicity models. Based on the support of traditional medicinal experience, its well-defined pharmacodynamic effects, relatively clear mechanism, and favorable preliminary safety profile, inermol acetate demonstrates the potential as a novel therapeutic agent for improving lipid metabolism disorders and related diseases (such as obesity, type 2 diabetes, insulin resistance, and atherosclerosis). This compound can achieve some degree of weight and metabolic regulation without relying on strict dietary restrictions.

[0019] Further pharmacodynamic studies have shown that inulin acetate may be converted into the metabolite inulinol via deacetylation during in vivo metabolism. Notably, both compounds exhibited significant fat reduction and weight regulation effects in animal models. The proto-carbon compound (inulin acetate) showed weaker activity in specific cell models, suggesting that its biological effects may depend on in vivo metabolic activation; while the metabolite (inulinol), as a potential active form, directly intervenes in lipid metabolism pathways (such as regulating hepatic nuclear receptors and gut microbiota), ultimately achieving a synergistic effect of reducing fat accumulation, improving hepatic lipid metabolism, and enhancing insulin sensitivity. Attached Figure Description

[0020] Figure 1 Body weight changes in mice modeled by gavage administration of phenol acetate followed by a 45% high-calorie, high-fat diet; black * indicates P < 0.05 between the model group and the control group; purple * indicates P < 0.05 between the low-dose group and the model group; red * indicates P < 0.05 between the medium-dose H group and the model group; green * indicates P < 0.05 between the high-dose group and the model group. LFD+V represents the control group, HFD+V represents the model group; HFD+25, HFD+50, and HFD+100 represent the low, medium, and high-dose groups, respectively. *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.0001.

[0021] Figure 2 Liver and adipose tissue weights in mice modeled by gavage administration of vinblastine acetate followed by a 45% high-calorie, high-fat diet; in the figure, Liver: mouse liver; EWAT: mouse epididymal fat; SubWAT: mouse subcutaneous fat; BAT: mouse brown adipose tissue. LFD+V represents the control group, HFD+V represents the model group; HFD+25, HFD+50, and HFD+100 represent low, medium, and high-dose administration groups, respectively. *P<0.05, **P<0.01, ***P<0.005, ****P<0.0001.

[0022] Figure 3 Liver lipid content in mice modeled by gavage administration of phenol acetate followed by a 45% high-calorie, high-fat diet; Figure A shows representative liver images for each group (small squares, 0.5 × 0.5 cm); liver tissue sections stained with HE (scale bar = 100 μm); liver tissue stained with Oil Red O (scale bar = 100 μm). Figure B shows the statistical chart of Oil Red O staining area. Figure C shows the triglyceride content in liver tissue. Figure D shows the cholesterol content in liver tissue. LFD+V represents the control group, HFD+V represents the model group; HFD+25, HFD+50, and HFD+100 represent the low, medium, and high-dose administration groups, respectively. *P<0.05, **P<0.01.

[0023] Figure 4 Insulin tolerance test in mice modeled by gavage administration of viniferin acetate followed by feeding with a 45% high-calorie, high-fat diet. In the figure, LFD+V represents the control group, HFD+V represents the model group; HFD+25, HFD+50, and HFD+100 represent the low, medium, and high dose groups, i.e., 25, 50, and 100 mg / kg, respectively; **P<0.01.

[0024] Figure 5 Acute toxicity test of inulin acetate in Kunming mice. *P<0.01 in the figure; acute toxicity results of 1000 mg / kg inulin acetate in mice. A represents mouse body weight. B represents food intake. C represents organ coefficient of mice.

[0025] Figure 6The 28-day toxicity study of inulin acetate included the results of mouse body weight, food intake, and organ index. In the figure, A represents the body weight of male mice; a magenta * indicates a difference of P < 0.05 between the 150 mg / kg inulin acetate group and the control group; an orange * indicates a difference of P < 0.05 between the 250 mg / kg inulin acetate group and the control group. B represents the food intake of male mice. C represents the organ coefficient of male mice. D represents the body weight of female mice; a green * indicates a difference of P < 0.05 between the 250 mg / kg inulin acetate group and the control group. E represents the food intake of female mice. F represents the organ coefficient of female mice. "Vehicle male" and "Vehicle female" represent the male and female control groups, respectively.

[0026] Figure 7 The results of the 28-day toxicity test of phenol acetate in mice, and the results of the liver pathological sections (Scalebar = 100 μm).

[0027] Figure 8 The effects of inotropic acetate and its derivative inotropic on adipogenesis in mouse preadipocytes 3T3-L1. Detailed Implementation

[0028] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the embodiments described below are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0029] Example 1: Extraction and separation of incensole acetate and incensole

[0030] The present invention uses the resin of Boswellia papyifera as the raw material for extraction, and the present invention does not limit the source of the raw material.

[0031] 100g of Boswellia papyifera resin was extracted four times with ethyl acetate at 18℃ using ultrasound, each time at a volume of 4, for 1.5 hours. The extracts were combined, and the solvent was removed under reduced pressure until no ester odor remained, yielding 75g of ethyl acetate extract. The dried extract was dissolved in ethyl acetate and mixed with silica gel. It was then eluted isocratically through 200-300 mesh silica gel (990g) with petroleum ether-dichloromethane (2:1, 3300mL). Each 300mL fraction was considered a separate fraction. Inermentol acetate was used as a control. The fractions rich in inermentol acetate were combined, and the solvent was removed under reduced pressure until dry; this fraction weighed 4.25g. This portion was dissolved again in ethyl acetate and mixed with silica gel. It was then eluted with 200-300 mesh silica gel (100g) and petroleum ether-dichloromethane (20:1, 550mL) to remove impurities. The elution was continued with petroleum ether-dichloromethane (10:1), with each 80mL fraction being a separate fraction. Using inulin acetate as a control, the fractions containing inulin acetate were combined, concentrated under reduced pressure, and dried to obtain 2.9g of pure product.

[0032] It should be noted that inotropic acetate can also be obtained from natural sources using other chromatographic methods guided by LC-MS, or it can be obtained through synthesis.

[0033] The characterization results of inotropic acetate are as follows:

[0034] 1 H NMR(CDCl3,500MHz)δ:5.17(t,J=6.0Hz,H-9,1H),5.16(t,J=5.9Hz,H-13,1H),4.87(d,J=10.3Hz,H-5,1H),2.19(m,H-10, 2H),2.18(m,H-11,1H),2.14(m,H-14,2H),2.13(m,H-11,1H),2.05(s,Me-22,3H),2.02(dd,J=14.5,5.1Hz,H-7,1H),1.90 (m,H-18,1H),1.87(m,H-3,1H),1.83(m,H-6,1H),1.75(dt,J=14.0,8.6Hz,H-2,1H),1.63(m,H-7,1H),1.60(m,H-2,1H),1 .59(s,Me-16,3H),1.59(m,H-3,1H),1.55(s,Me-17,3H),1.50(m,H-6,1H),1.11(s,Me-15,3H),0.90(d,J=6.8Hz,Me-19or H-20,3H),0.89(d,J=6.8Hz,Me-19or H-20,3H).

[0035] 13C NMR(CDCl3,125MHz)δ:171.3(C-21),135.4(C-12),133.3(C-8),125.5(C-9) ,121.2(C-13),89.4(C-1),83.2(C-4),76.7(C-5),38.6(C-11),35.7(C-3), 35.0(C-18),33.5(C-7),32.1(C-14),30.4(C-2),27.9(C-6),24.9(C-10),2 2.2(C-15),21.4(C-22),18.2(C-20),18.1(C-19),17.8(C-16),16.2(C-17).

[0036] Inermentol was obtained by hydrolyzing inermentol acetate, and the characterization results are as follows:

[0037] 1 H NMR(CDCl3,500MHz)δ:5.11(t,J=6.3Hz,H-13,1H),5.07(t,J=7.1Hz,H-9,1H),3.30(d,J=10.1Hz,H-5,1H),2.21(m,H-14,1H),2.18(m ,H-10,2H),2.12(m,H-7,1H),2.10(m,H-14,2H),2.05(m,H-3,1H),2.03(m,H-14,1H),1.99(dd,J=13.9,1.8Hz,H-7,1H),1.90(m,H-18 ,1H),1.87(m,H-6,1H),1.82(dt,J=12.2,8.0Hz,H-2,1H),1.74(ddd,J=12.3,8.0,4.6Hz,H-3,1H),1.62(s,H-16,3H),1.58(ddd,J=12 .2,7.9,4.6Hz,H-2,1H),1.51(s,H-17,3H),1.32(dddd,J=13.9,10.1,5.4,1.8Hz,H-6,1H),1.07(s,H-4,3H),0.91(d,J=6.9Hz,H-19or H-20,3H),0.90(d,J=6.8Hz,H-19or H-20,3H).

[0038] 13C NMR(CDCl3,125MHz)δ:134.4(C-8),134.3(C-12),125.3(C-9),121.9(C-13),88.7(C-1),84.3(C-4),75.7(C-5),38.7(C-11),36.5(C-3),3 4.9(C-18),33.8(C-7),32.5(C-14),30.8(C-6),30.7(C-2),24.9(C- 10),20.8(C-17),18.3(C-19),18.2(C-20),18.1(C-16),16.3(C-15).

[0039] To better understand this invention, the following experimental examples use inulin acetate nanoparticles to administer to animal models to verify the fat-reducing effect of inulin acetate, but this is not intended to limit the invention.

[0040] Experiment 1: Investigating the effects of inotropic acetate in animal models

[0041] (1) Experimental principle: A high-fat diet causes mice to ingest excessive amounts of lipids and other nutrients, which induces the accumulation of a large amount of fat in the organs and tissues of the mice, resulting in lipid metabolism disorder.

[0042] (2) Experimental method: Mice were kept in an SPF-grade animal room and were allowed to eat and drink freely. Mice were randomly assigned to different diets based on body weight: a low-fat diet group (fed a diet containing 10% fat and administered an empty vector via gavage), a high-fat diet group (fed a diet containing 45% fat and administered an empty vector via gavage), and a high-fat diet group (fed a diet containing 45% fat and administered an empty vector via gavage). Mice were also given low (25 mg / kg), medium (50 mg / kg), and high (100 mg / kg) doses of inopropyl acetate nanoparticles via gavage. The doses of 25, 50, and 100 mg / kg corresponded to the mass of the inopropyl acetate compound. Mice were gavaged once daily, and their body weight was measured weekly for 18 weeks. Mice were euthanized, and their plasma and organs were collected and weighed. During the 18-week period, mice were fasted for 6 hours to perform an insulin tolerance test (0.75 IU / kg insulin was injected intraperitoneally, and blood was collected from the tail of the mouse at 0, 15, 30, 60, 90, and 120 minutes to measure glucose concentration).

[0043] Preparation method of nano-formulation: 0.45 g of inulin acetate and 0.15 g of vitamin E polyethylene glycol succinate (TPGS) were weighed and dissolved in ethanol solution. Under magnetic stirring at 500 r / min, the solution was slowly added dropwise to 15 mL of deionized water. The organic solvent was removed by rotary evaporation at 45 °C and 0.12 mbar, and the solution was further concentrated to an appropriate volume to obtain inulin acetate nano-formulation. The content of inulin acetate in the nano-formulation was determined to be 40.3 mg / mL using high-performance liquid chromatography. The particle size of the nano-formulation was measured as size = 196.7 ± 5.27 nm, and the PDI was 0.105 ± 0.014.

[0044] (3) Experimental results: Mouse body weight, organ weight, liver lipid content, and insulin-injected blood glucose levels were as follows: Figure 1-4 As shown.

[0045] Figure 1 In the study, after administration of inotropic acetate nanoparticles, the body weight of the medium-dose group (50 mg / kg) and the high-dose group (100 mg / kg) was significantly lower than that of the model group (red P<0.05, green P<0.05), with the high-dose group showing the largest decrease (****P<0.0001). This indicates that inotropic acetate, within the dose range of 50–100 mg / kg, dose-dependently inhibits high-fat diet-induced weight gain.

[0046] Figure 2 In the control group (especially 50 / 100 mg / kg), liver, EWAT, and SubWAT weights were significantly reduced (P<0.05 to ***P<0.0001), while brown adipose tissue (BAT) weight showed no significant change. This indicates that inotropic acetate effectively reduces lipid accumulation in the liver and white adipose tissue of mice on a high-fat diet.

[0047] Figure 3 Morphological observation showed that the liver in the model group exhibited significant steatosis (gross yellowing, lipid droplets visible in HE staining, and increased Oil Red O staining positive area), while the degree of steatosis was reduced in the treatment groups (especially the 50 / 100 mg / kg group). Quantitative analysis of the Oil Red O positive area showed that the model group had a significantly higher area than the control group, while the treatment group (50 / 100 mg / kg) had a significantly lower area (*P<0.05, **P<0.01). Liver triglyceride (TG) and total cholesterol (TC) levels were significantly increased in the model group and significantly decreased in the medium- and high-dose treatment groups (*P<0.05, **P<0.01). This indicates that phenol acetate dose-dependently improves high-fat diet-induced liver lipid accumulation.

[0048] Figure 4In the insulin tolerance test (ITT), the model group (HFD+V) showed significantly lower glucose clearance than the control group (LFD+V). The area under the blood glucose curve in the treated group (50 / 100 mg / kg) was significantly smaller than that in the model group (**P<0.01), indicating improved insulin sensitivity. This suggests that high doses of inosinate can improve insulin resistance in mice on a high-fat diet.

[0049] from Figure 1-4 The results showed that cinnamyl acetate significantly reduced weight gain (dose-dependent), reduced liver and white adipose tissue mass, inhibited liver lipid accumulation (reduced TG / TC content and improved tissue lipidation), and enhanced insulin sensitivity.

[0050] Test Example 2: Acute toxicity test of inotropic acetate:

[0051] (1) Experimental Methods: Based on the above experiments, the effective dose range of inosinate acetate was determined to be between 50-100 mg / kg. Therefore, the acute toxicity experiment was conducted by a single gavage administration. Kunming female mice, 6 weeks old, 18-22g, were purchased from Speford (Beijing) Biotechnology Co., Ltd. Animals were administered 1000 mg / kg and a normal control group (solvent). Inosinate acetate and vitamin E polyethylene glycol succinate (TPGS) in a weight ratio of 3:1 were dissolved in anhydrous ethanol (the concentration of inosinate acetate was approximately 0.3 g / mL). The solution was slowly dripped into 7.5 times the volume of deionized water under magnetic stirring at room temperature and 500 r / min. The organic solvent was removed by rotary evaporation under reduced pressure at 45℃ to obtain inosinate acetate nano-suspension. Particle size was determined: 194.4 ± 2.964 nm, polydispersity index (PDI) = 0.182. Accurately measure 0.2 mL of a well-mixed solution of inulin acetate nanoparticles into a 1 mL volumetric flask, dissolve in chromatographic methanol, and dilute to the mark (5-fold dilution). Inject 20 μL of the solution into the HPLC sample for analysis. The content of inulin acetate in the nanoparticle formulation was determined to be 28.0946 mg / mL. Mice were administered the solution by gavage at a dose of 1000 mg / kg and observed for 14 days. Mice were weighed and fed. They were sacrificed at the end of day 14, and samples were collected from each group for pathological examination.

[0052] (2) Experimental results are shown in Figure 5 Throughout the study period, the normal group mice showed normal coat color, skin color, activity, mental state, weight changes, and food intake. The drug-treated group mice exhibited symptoms of quietness, abdominal convulsions, unusual vocalizations, prone position, and rapid breathing. On the second day, one mouse in the drug-treated group died. On the seventh day, the drug-treated group mice showed a significant decrease in body weight. Figure 5 A). There was no significant difference in food intake between the treatment group and the control group. Figure 5B). Visual inspection of the five major organs—liver, heart, spleen, lungs, and kidneys—revealed no obvious abnormalities, and organ indices showed no significant abnormalities. Figure 5 C). Therefore, due to the LD50 of phenol acetate... 50 >1000mg / kg. Some changes in indicators observed in the acute toxicity test may be related to excessively high doses. However, considering the results of the subacute toxicity test (similar to simulated long-term toxicity) below, no significant abnormalities were observed in the subacute toxicity test, suggesting good safety at therapeutic doses.

[0053] Test Example 3: 28-day toxicity test of inotropic acetate:

[0054] (1) Experimental method: Based on the above acute toxicity test, the LD50 of inotropic acetate was basically determined. 50 >1000mg / kg. Therefore, the 28-day toxicity experiment used continuous gavage administration. Kunming mice, half male and half female, 6 weeks old, 18-22g, were purchased from Spiefol (Beijing) Biotechnology Co., Ltd. The dosage of the nano-formulation administered to animals was the equivalent weight of the inotropic acetate compound, i.e., 150mg / kg, 250mg / kg, and a normal control group (solvent). The inotropic acetate nanoparticles were from the same batch as in Experiment 3. Mice were weighed weekly for 28 days, and their feed intake was also measured. Mice were sacrificed on day 28. Plasma was collected for complete blood count, serum was collected for biochemical analysis, and heart, liver, spleen, stomach, kidney, brain, adipose tissue, and reproductive organs were collected for observation. Liver sections were used for pathological examination.

[0055] (2) Experimental Results: Throughout the study period, the fur of mice in all groups remained smooth, and there were no significant differences in fecal morphology. No mice in any group died. One-way ANOVA was used to analyze the body weight of mice treated with phenol acetate and those in the control group. It was found that male mice in the 250 mg / kg dose group showed a significant decrease in body weight after week 1 of administration, and male mice in the 150 mg / kg dose group showed a significant decrease in body weight after week 2 of administration. For female mice, a significant decrease in body weight at the 250 mg / kg dose was only detected at day 28. Figure 6 (A, D). Compared with the control group, there was no statistically significant change in food consumption ( Figure 6 (B, E). Major organelles of the mice, including brain, liver, kidney, heart, spleen, epididymis, testis, uterus, and ovary, were isolated and accurately weighed. A significant increase in the relative weight of the liver was observed in male mice treated with the drug, and a similar trend was observed in female mice. At a dose of 250 mg / kg, the relative weight of the brain in male mice was significantly increased; however, this was still within the mouse reference range (B, E). Figure 6 The relative weights of other organs in mice did not change significantly (C, F). Figure 6(C, F). For hematological analysis, compared to the control group, female mice treated with inulin acetate showed a significant decrease in red blood cell count and a significant increase in hemoglobin. At a dose of 150 mg / kg, both male and female mice showed a significant increase in platelet count, and at a dose of 250 mg / kg, both male and female mice showed a significant increase in platelet distribution width, but all remained within normal reference values. Other parameters showed no significant differences (Table 1). For clinical biochemical analysis, there were no statistically significant changes in serum biochemical parameters in male mice; however, compared to the control female mice, the female mice treated with inulin acetate showed a significant decrease in total bilirubin and albumin, and a significant increase in cholesterol. At a dose of 150 mg / kg, glucose levels were significantly increased, but this was not dose-dependent. Some differences were observed in serum biochemical indicators in female mice, but all remained within normal reference values. Notably, compared with the control group, there were no significant differences in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urinary nitrogen (UREA), and creatinine (CREA) levels in male and female mice, indicating that the inotropic acetate compound has no significant hepatotoxicity or nephrotoxicity (Table 2). Pathological sections of the mice showed no significant abnormalities in the liver. Figure 7 The subacute toxicity (similar to simulated long-term toxicity) test results showed no significant abnormalities, indicating good safety at therapeutic doses.

[0056] Table 1. Results of routine blood tests in mice.

[0057]

[0058]

[0059] Data are expressed as mean ± SD. n = 6–7 / sex / group. Compared with the control group, *P < 0.05, **P < 0.01, ****P < 0.0001.

[0060] The results of the 28-day toxicity test of phenol acetate in mice and the biochemical analysis results.

[0061] Table 2 Results of serum biochemical indicators in mice.

[0062]

[0063] Data are expressed as mean ± SD. n = 6–7 / sex / group. Compared with the control group, *p < 0.05, **p < 0.01, ****p < 0.0001.

[0064] Experimental Example 4: Effects of inermol acetate and inermol on adipogenesis in mouse preadipocytes 3T3-L1.

[0065] Experimental principle: The 3T3-L1 adipogenesis induction model is based on stimulating the differentiation of preadipocytes into mature adipocytes in vivo through a combination of specific hormones and chemicals.

[0066] Experimental Methods: Resuscitate 3T3-L1 cells. Culture conditions: Expansion medium (10% fetal bovine serum + DMEM high-glucose medium + 1% penicillin-streptomycin). Once cells reach approximately 70% confluence, passage them. After sufficient cell volume, seed them into 12-well plates (2x10⁶ cells / well). 5 Cells were cultured in wells for 48 hours until they reached full confluence. The medium was then changed, and the cells were cultured in expansion medium for another 48 hours (day 0). After 48 hours, the medium was changed to differentiation medium (10% fetal bovine serum + DMEM high-glucose medium + 1% penicillin-streptomycin + 1.0 μM Dexamethasone + 0.5 mM IBMX + 10 μg / mL Insulin + 2 μM Rosiglitazone) and cultured for another 48 hours (day 2). After 48 hours, the medium was changed again, and the cells were cultured in maintenance medium (10% fetal bovine serum + DMEM high-glucose medium + 1% penicillin-streptomycin + 10 μg / mL Insulin) (day 4). The maintenance medium was changed every 48 hours. By day 14, most cells had been induced to differentiate. The cells were fixed, stained with Oil Red stained, photographed, and semi-quantitatively analyzed. During cell differentiation, the compound was added starting from day 0, and added with each subsequent medium change.

[0067] Experimental results: The effects of inulin acetate and inulin on the adipogenic model of mouse preadipocytes 3T3-L1 are shown in the figure. Figure 8 .

[0068] The Oil Red O staining results and semi-quantitative analysis in the figure show that inulin acetate and inulinol inhibited adipogenic differentiation in the 3T3-L1 cell adipogenic differentiation model (control group: DMSO group), indicating that high concentrations of inulin acetate and inulinol can significantly inhibit adipogenesis. "**" p<0.01.

[0069] The above experimental results show that the compounds of the present invention, inermine acetate and inermine, have significant effects in improving lipid metabolism, insulin resistance, and weight loss, and do not show obvious toxicity. They are relatively safe and can be used to treat lipid metabolism disorder-related diseases (obesity, insulin resistance, type 2 diabetes, and atherosclerosis, etc.).

[0070] Application Example 1:

[0071] Inocyanate acetate and inocyanate were prepared into oral nano-formulations according to conventional methods and dosages.

[0072] Application Example 2:

[0073] Take 1 part of inotropic acetate, 20 parts of vinyl acetate resin with a degree of polymerization of 300, 2 parts of butyl phthalate, 3 parts of carnauba wax and 20 parts of maltose, mix them in a mixer at 50°C for 3 minutes, then add 50 parts of sugar and 1 part of mint, mix evenly, and then extrude the chewing gum from the extruder at a constant temperature of 50°C. Cut it into the specified thickness as a functional food.

[0074] In the above embodiments, the descriptions of each embodiment have different focuses. For parts that are not described in detail in a certain embodiment, please refer to the relevant descriptions in other embodiments.

[0075] The above description describes specific embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of various equivalent modifications or substitutions within the technical scope disclosed in the present invention, and these modifications or substitutions should all be covered within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. Use in the preparation of medicaments for the prevention, improvement and / or treatment of diseases or conditions associated with lipid metabolism disorders, of inulin acetate represented by formula (I), inulin represented by formula (II), or pharmaceutically acceptable salts or esters of both.

2. Use of inulin acetate represented by formula (I), inulin represented by formula (II), or a pharmaceutically acceptable salt or ester of both, in the preparation of food or functional health products for the prevention, improvement and / or treatment of non-disease symptoms associated with lipid metabolism disorders.

3. The use as described in claim 1, characterized in that, The diseases or conditions associated with lipid metabolism disorders are selected from one or more of the following: obesity, metabolic-associated fatty liver disease, diabetes, and atherosclerosis.

4. The use as described in claim 2, characterized in that, The non-disease symptoms associated with lipid metabolism disorders are selected from one or more of the following: obesity, liver damage, abnormal blood glucose levels, and abnormal blood lipid levels.

5. The use as described in claim 1 or 3, characterized in that, The drug is an injection, tablet, powder, granule, pill, capsule, oral liquid, ointment, cream, nano-formulation, or spray.

6. The use as described in claim 2 or 4, characterized in that, The food or functional health product mentioned refers to oral liquid, tea, lozenges, capsules, beverages, effervescent tablets, or chewable tablets.

7. The use as described in any one of claims 1-6, characterized in that, The inermine acetate and / or inermine are in the form of a pharmaceutical composition or a functional health food composition, wherein the pharmaceutical composition comprises the inermine acetate and / or inermine, or a pharmaceutically acceptable salt or ester of both, and one or more pharmaceutically acceptable excipients; and the functional health food composition comprises the inermine acetate and / or inermine, or a pharmaceutically acceptable salt or ester of both, and one or more food-acceptable excipients.

8. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises inulin acetate and / or inulin as described in any one of claims 1-7, or a pharmaceutically acceptable salt or ester of both, and one or more pharmaceutically acceptable excipients.

9. A functional health food composition, characterized in that, The functional health food composition comprises inulin acetate and / or inulin as described in any one of claims 1-7, or a pharmaceutically acceptable salt or ester of both, and one or more food-acceptable excipients.

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