A composition containing arctiopolysaccharide for reducing blood sugar of type 2 diabetes patients and its preparation method and application

Abstract

The application discloses a composition containing burdock polysaccharide for reducing blood sugar of type 2 diabetes patients and a preparation method and application thereof, and belongs to the technical field of medicine and food. The composition contains burdock polysaccharide, chitooligosaccharide, chlorogenic acid, epicatechin, resveratrol, ginsenoside Rd, and vitamin D, vitamin B1, vitamin B6, vitamin B12, magnesium glycinate and thaumatin protein. The application takes burdock polysaccharide as a core long-acting component, takes chitooligosaccharide as a short-acting synergistic component, constructs a long-short-acting synergistic blood sugar reducing system, and realizes the organic combination of rapid blood sugar reduction and stable blood sugar control. Experiments show that the composition can significantly reduce the fasting blood sugar of type 2 diabetes model rats, improve insulin resistance and glucose tolerance, reduce blood lipid and inflammatory factor levels, and reduce oxidative stress damage. The alpha-glucosidase inhibitory activity and in-vivo comprehensive blood sugar reducing effect of the composition are better than those of single burdock polysaccharide, and the composition has good taste and is suitable for long-term use of diabetes patients.

Description

Technical Field

[0001] This invention relates to the fields of medicine and food technology, specifically to a hypoglycemic composition with plant-extracted burdock polysaccharide as the core active ingredient, combined with chitosan oligosaccharide, polyphenolic compounds, ginsenosides, and various vitamins and minerals, as well as its preparation method and its application in assisting in lowering blood sugar in patients with type 2 diabetes. Background Technology

[0002] Type 2 diabetes is a metabolic disease characterized by insulin resistance and relative insulin insufficiency. Clinically, it is often accompanied by glucose and lipid metabolism disorders, increased oxidative stress, and the occurrence and development of various chronic complications. Currently used oral hypoglycemic agents, including alpha-glucosidase inhibitors, biguanides, and sulfonylureas, can control blood sugar to some extent, but long-term use can easily cause adverse reactions such as gastrointestinal discomfort and liver and kidney damage. Furthermore, these drugs are expensive, making it difficult to meet patients' needs for safety, tolerability, and affordability for long-term use. In addition, existing drugs mostly focus on immediate or short-term blood sugar control, with relatively insufficient attention paid to providing stable and long-term blood sugar regulation to reduce target organ damage caused by blood sugar fluctuations. In recent years, polysaccharides, flavonoids, and saponins derived from natural products have shown promising applications in the adjunctive treatment of diabetes, becoming an important direction for the research and development of functional foods and drugs.

[0003] Burdock (Arctium lappa L.) is a herbaceous plant belonging to the Asteraceae family. Its roots are rich in various active ingredients such as inulin-type polysaccharides, flavonoids, polyphenols, and volatile oils, possessing multiple biological functions including antioxidant, immunomodulatory, and gut microbiota improvement. Burdock polysaccharide (ALI) is a water-soluble, low-molecular-weight inulin-type fructan extracted from burdock roots. Studies have confirmed that it possesses multiple pharmacological activities, including inhibiting α-glucosidase activity, antioxidant effects, improving glucose and lipid metabolism, and protecting liver and kidney function. In particular, as a water-soluble dietary fiber and polysaccharide, burdock polysaccharide is not rapidly absorbed by the upper digestive tract in the body. Instead, it exerts a long-lasting and stable glycemic regulation effect through pathways such as regulating gut microbiota, continuously inhibiting glycosidase activity, and improving insulin sensitivity. Existing patents such as CN202010098242.4, which relates to the application of burdock polysaccharide in the treatment of non-alcoholic fatty liver disease, CN202411292708.9, which relates to its use in the preparation of drugs for pulmonary arterial hypertension, and CN202411821584.9, which discloses its potential in the treatment of cognitive impairment, have not systematically studied the relationship between the extraction process, molecular structure and hypoglycemic activity of burdock polysaccharide, nor have they seen any reports of its compounding with chitosan oligosaccharide, polyphenols, ginsenosides and other components for synergistic hypoglycemic effects, and there is no research on the optimization of compound formulations based on its long-acting characteristics.

[0004] Chitooligosaccharides, as degradation products of chitosan, possess excellent water solubility and bioactivity. Recent studies have confirmed their hypoglycemic effects through multiple target pathways: chitooligosaccharides can improve insulin resistance in HepG2 cells by activating the AKT / GLUT4 signaling pathway, effectively reducing fasting blood glucose and lipid levels in type 2 diabetic mice and improving glucose tolerance. Furthermore, chitooligosaccharides can protect against complications such as diabetic nephropathy by activating the AMPK signaling pathway, inhibiting the oxidative stress-fibrosis axis, and regulating intestinal barrier function. Notably, compared to burdock polysaccharides, chitooligosaccharides, due to their smaller molecular weight and better water solubility, can be rapidly absorbed by the gastrointestinal tract. By activating key signaling pathways, they rapidly improve the uptake and utilization of glucose in peripheral tissues, exhibiting a rapid onset and direct, short-acting hypoglycemic effect. However, there are currently no reports on the scientific combination of burdock polysaccharides, which have long-acting regulatory properties, with short-acting chitooligosaccharides.

[0005] Chlorogenic acid, an ester compound formed from caffeic acid and quinic acid, is widely found in plants such as honeysuckle and eucommia. It has antioxidant, anti-inflammatory, glucose and lipid metabolism regulating, and insulin resistance-improving effects. Epicatechin is a major flavanol compound in tea, which enhances insulin sensitivity and improves vascular function. Resveratrol, a polyphenol found in plants such as grapes and Polygonum cuspidatum, has been shown to activate AMPK, improve insulin resistance, and has anti-inflammatory and antioxidant effects. Ginsenoside Rd is one of the main active ingredients of ginseng, which promotes insulin secretion, protects pancreatic β-cells, and improves insulin resistance.

[0006] Vitamin D and B vitamins (B1, B6, B12) are coenzymes for key enzymes in glucose metabolism, participating in energy metabolism and maintaining nerve function. Magnesium ions, as cofactors for many enzymes, participate in glucose transport and insulin signaling. Magnesium glycine is characterized by high bioavailability and low gastrointestinal irritation. Furthermore, plant extracts often have unpleasant flavors, affecting patient adherence to long-term use. Semabin, as a natural sweet protein, possesses excellent properties of high sweetness, low calories, and no blood sugar elevation, making it suitable for improving the taste of diabetic functional foods and enhancing product acceptability.

[0007] In summary, the existing technology lacks a hypoglycemic composition that uses burdock polysaccharide as the core long-acting component, chitosan oligosaccharide as the short-acting synergistic component, and combines multiple natural active products and nutrients to overcome the shortcomings of existing hypoglycemic products in terms of single duration of action, insufficient synergy, and incomplete nutritional support. Summary of the Invention

[0008] The present invention aims to provide a hypoglycemic composition with burdock polysaccharide as the core long-acting component, chitosan oligosaccharide as the short-acting synergistic component, and combined with chlorogenic acid, epicatechin, resveratrol, ginsenoside Rd, and various vitamins and minerals, so as to achieve an organic combination of rapid hypoglycemia and stable blood sugar control, and overcome the shortcomings of existing hypoglycemic products with single-term effects.

[0009] This invention provides a composition containing burdock polysaccharide for lowering blood glucose in patients with type 2 diabetes, comprising active ingredients and excipients; the active ingredients include burdock polysaccharide, chitosan oligosaccharide, chlorogenic acid, epicatechin, resveratrol, and ginsenoside Rd; the excipients include vitamin D, vitamin B1, vitamin B6, vitamin B12, magnesium glycine, and sematriol.

[0010] Preferably, the components in the composition are, by weight, the following: 30-70 parts burdock polysaccharide; 10-40 parts chitosan oligosaccharide; 5-15 parts chlorogenic acid; 3-12 parts epicatechin; 2-10 parts resveratrol; 1-8 parts ginsenoside Rd; 0.001-0.01 parts vitamin D; 0.01-0.1 parts vitamin B1; 0.01-0.1 parts vitamin B6; 0.0001-0.002 parts vitamin B12; 0.5-2 parts magnesium glycine; and 0.1-2 parts sematriol.

[0011] Further, by weight, the contents of each component are as follows: burdock polysaccharide 50 parts; chitosan oligosaccharide 25 parts; chlorogenic acid 10 parts; epicatechin 8 parts; resveratrol 6 parts; ginsenoside Rd 5 parts; vitamin D 0.005 parts; vitamin B1 0.05 parts; vitamin B6 0.05 parts; vitamin B12 0.0008 parts; glycine magnesium 1 part; sematriol 0.5 parts.

[0012] Preferably, the molecular weight of the chitosan oligosaccharide is 1000-2000 Da.

[0013] Furthermore, the molecular weight of the chitosan oligosaccharide is 1500 Da.

[0014] Preferably, the burdock polysaccharide is prepared by the following method:

[0015] S1. Take fresh burdock root, wash it, blanch it in hot water at 90-100℃ for 3-8 minutes, peel it, cut it into sections, press it, and collect the juice and burdock residue separately.

[0016] S2. Add hot water at 50-80℃ to the burdock residue at a solid-liquid ratio of 1:10 to 1:30 (g / mL), soak for 20-40 minutes, and press again while hot. Repeat 1-2 times.

[0017] S3. Combine all extracts, centrifuge and filter, concentrate the filtrate to 1 / 5 to 1 / 10 of the original volume, add 2 to 4 times the volume of 95% ethanol, let stand at 4°C for 12 to 18 hours, and centrifuge to collect the precipitate.

[0018] S4. Redissolve the precipitate in water, add 0.5% to 1.5% (w / v) of papain, and enzymatically hydrolyze at pH 6.0 to 6.5 and 55°C for 3 hours. Boil for 10 minutes to inactivate the enzyme, centrifuge to remove the precipitate, and treat the supernatant with Sevage reagent by shaking 1 to 2 times. Then decolorize with D101 macroporous adsorption resin.

[0019] S5. Dilute the decolorized polysaccharide solution to a concentration of 5-10 g / L, and concentrate it to 1 / 3-1 / 5 of the original volume using an ultrafiltration membrane with a molecular weight cutoff of 1000 Da. Then add an equal volume of ultrapure water for washing and filtration, repeating 3-4 times. Collect the retentate. After concentration under reduced pressure, dry the retentate to obtain burdock polysaccharide.

[0020] Preferably, the dosage form of the composition is a powder or tablet.

[0021] The present invention also provides a method for preparing the aforementioned composition, comprising the following steps:

[0022] (1) Weigh out the following ingredients by weight: burdock polysaccharide, chitosan oligosaccharide, chlorogenic acid, epicatechin, resveratrol, ginsenoside Rd, vitamin D, vitamin B1, vitamin B6, vitamin B12, magnesium glycine and sematriol;

[0023] (2) Crush each raw material and pass it through an 80-120 mesh sieve;

[0024] (3) Place the pulverized raw materials in a mixer and mix thoroughly until homogeneous;

[0025] (4) Sterilize the mixture and package it according to specifications to obtain powder; or sterilize the mixture and compress it into tablets to obtain tablets.

[0026] The present invention also provides the use of the above-described composition in the preparation of pharmaceuticals or functional foods for lowering blood glucose in patients with type 2 diabetes.

[0027] Furthermore, the application is the use of the composition in the preparation of pharmaceuticals or functional foods having at least one of the following uses: lowering fasting blood glucose, improving insulin resistance, improving glucose tolerance, lowering blood lipids, lowering inflammatory factor levels, and reducing oxidative stress damage.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] (1) This invention uses burdock polysaccharide as the core long-acting active ingredient. Through its sustained effects of inhibiting α-glucosidase, regulating intestinal microecology, anti-oxidation, anti-inflammation, and improving glucose and lipid metabolism, it exerts a stable and long-lasting hypoglycemic effect. Experimental results show that burdock polysaccharide alone can reduce fasting blood glucose in diabetic model rats from 23.13 mmol / L to 16.45 mmol / L (P<0.05), demonstrating its long-term basic blood glucose control ability.

[0030] (2) This invention creatively introduces chitosan oligosaccharide as a short-acting active component, forming a new hypoglycemic mode of "long-term and short-term synergistic effect" with burdock polysaccharide. Chitosan oligosaccharide has a small molecular weight and good water solubility, which can be rapidly absorbed by the body and activate key signaling pathways such as AKT / GLUT4 and AMPK, thereby improving insulin resistance and promoting glucose uptake in an immediate manner, making up for the relatively slow onset of action of burdock polysaccharide, and achieving an organic combination of rapid hypoglycemic effect and long-term stabilization. In the oral glucose tolerance test, the blood glucose level of the medium-dose group of the composition of this invention was 15.41 mmol / L 120 min after gavage glucose administration, which was significantly lower than that of the model group of 22.83 mmol / L (P<0.01), and the area under the blood glucose curve was also significantly reduced, showing excellent postprandial blood glucose management ability;

[0031] (3) The present invention combines chlorogenic acid, epicatechin, resveratrol and other polyphenolic compounds and ginsenoside Rd to enhance the comprehensive effects of hypoglycemia, insulin resistance, blood lipid regulation and anti-inflammatory and antioxidant effects through multi-target synergistic enhancement. Experimental data show that, compared with the burdock polysaccharide group alone, the medium-dose group of the composition of the present invention showed statistically significant advantages in improving insulin resistance index (HOMA-IR decreased by 60.71%), increasing insulin sensitivity index (ISI increased by 131.37%), reducing serum total cholesterol, triglycerides and free fatty acid levels, and reducing inflammatory factors such as high-sensitivity C-reactive protein (hs-CRP), α-tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) (P<0.05 or P<0.01). In vitro experiments further confirmed that the α-glucosidase inhibitory activity (IC50=0.3189 mg / mL) of the composition of the present invention was significantly better than that of burdock polysaccharide alone (IC50=0.4651 mg / mL) and the positive control acarbose, indicating that there is a synergistic effect among the components;

[0032] (4) This invention comprehensively supplements the nutrients that diabetic patients are prone to lack. B vitamins (B1, B6, B12) participate in energy metabolism as coenzymes of key enzymes in glucose metabolism, vitamin D improves insulin sensitivity, and magnesium glycine participates in glucose transport and insulin signal transduction as an insulin cofactor. It also has high bioavailability and low gastrointestinal irritation.

[0033] (5) This invention uses semaphore protein as a natural sweet protein, which, when used in combination with plant extracts, can significantly improve the unpleasant flavor of the composition, increase patient compliance with long-term use, and does not cause hyperglycemia. Taste evaluation tests showed that after adding semaphore protein, the taste score increased from 4.1±0.8 points to 8.9±1.6 points, and the acceptability was greatly improved;

[0034] (6) The composition of the present invention can be prepared as powder or tablet, which is convenient to take and easy to carry, and is suitable for long-term use by diabetic patients.

[0035] In summary, the hypoglycemic composition of the present invention provides a more comprehensive and effective auxiliary hypoglycemic solution than existing technologies through synergistic effects of "long-acting + short-acting", integrated regulation of multiple components, multiple targets and multiple pathways, systematic supplementation of nutrients and optimization of taste. Attached Figure Description

[0036] Figure 1 The results are shown in the graphs. A is the glucose tolerance curve of the composition in diabetic rats; B is the statistical result of the area under the blood glucose curve of the composition in diabetic rats.

[0037] Figure 2 The results are shown in the graphs of the effects of the composition on insulin resistance in diabetic rats; where A is the HOMA-IR graph and B is the ISI graph.

[0038] Figure 3 The results are shown in the graphs of the effects of the composition on blood lipids in diabetic rats; where A is the statistical graph of serum total cholesterol (TC), B is the statistical graph of serum triglycerides (TG), and C is the statistical graph of serum free fatty acids (FFA).

[0039] Figure 4 The results are shown in the figure of the effect of the composition on inflammatory factors in diabetic rats; where A is the statistical graph of serum high-sensitivity C-reactive protein (hs-CRP), B is the statistical graph of serum α-tumor necrosis factor (TNF-α), and C is the statistical graph of serum interleukin-6 (IL-6).

[0040] Figure 5 The results are shown in the figure of the effect of the composition on pancreatic oxidative stress in diabetic rats; where A is the statistical graph of superoxide dismutase (SOD), B is the statistical graph of glutathione peroxidase (GSH-PX), and C is the statistical graph of malondialdehyde (MDA).

[0041] Figure 6 The graph shows the results of the in vitro inhibitory activity of the composition against α-glucosidase; where A is the inhibition activity curve and B is the relevant parameter table. Detailed Implementation

[0042] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0043] Example 1: Preparation of burdock polysaccharide

[0044] Take 20 kg of fresh burdock root, wash it, blanch it in 100℃ hot water for 5 minutes, peel and cut it into sections. Use an automated multi-directional extruder to fully extract the juice from the burdock root, and collect the juice and burdock residue separately. Add the obtained burdock residue to 75℃ hot water at a solid-liquid ratio of 1:20 (g / mL), extract for 30 minutes, and press it a second time while it is still hot. Repeat this extraction and pressing operation twice. Combine all the extracts, centrifuge and filter them using a bag centrifuge, concentrate the filtrate to 1 / 5 of the original volume using a single-effect evaporator, add 3 times the volume of 95% ethanol, let it stand at 4℃ for 14 hours, and collect the precipitate by centrifugation using a disc centrifuge. Redissolve the precipitate in water, add 1% (w / v) papain, adjust the pH to 6.2, enzymatically hydrolyze it in a 55℃ water bath for 3 hours, boil for 10 minutes to inactivate the enzyme, and centrifuge at 5000 r / min for 10 minutes to remove the precipitate. The supernatant was deproteinized twice by shaking with Sevage reagent (a mixture of chloroform and n-butanol in a 4:1 volume ratio). Decolorization was performed using D101 macroporous adsorption resin. The decolorized polysaccharide solution was diluted to approximately 8 g / L and concentrated to 1 / 4 of its original volume using a regenerated cellulose ultrafiltration membrane with a molecular weight cutoff of 1000 Da. An equal volume of ultrapure water was then added for washing, and this process was repeated four times. The retentate was collected. After vacuum concentration, the retentate was dried using a low-temperature spray dryer at an inlet temperature of 45–65 °C and an outlet temperature of 25–40 °C to obtain white flocculent burdock polysaccharide.

[0045] Example 2: Preparation of low-dose hypoglycemic composition powder

[0046] Weigh the following components by weight: 30 parts burdock polysaccharide, 10 parts chitosan oligosaccharide (molecular weight 1500 Da), 5 parts chlorogenic acid, 3 parts epicatechin, 2 parts resveratrol, 1 part ginsenoside Rd, 0.001 parts vitamin D, 0.01 parts vitamin B1, 0.01 parts vitamin B6, 0.0001 parts vitamin B12, 0.5 parts magnesium glycine, and 0.5 parts thomaline. Grind each raw material separately through a 100-mesh sieve, place them in a three-dimensional mixer, and mix for 30 minutes until homogeneous. Sterilize the mixture by irradiation, and package according to specifications to obtain the low-dose hypoglycemic powder composition.

[0047] Example 3: Preparation of a medium-dose hypoglycemic composition powder

[0048] The following components were weighed according to their respective weight proportions: 50 parts burdock polysaccharide, 25 parts chitosan oligosaccharide (molecular weight 1500 Da), 10 parts chlorogenic acid, 8 parts epicatechin, 6 parts resveratrol, 5 parts ginsenoside Rd, 0.005 parts vitamin D, 0.05 parts vitamin B1, 0.05 parts vitamin B6, 0.0008 parts vitamin B12, 1 part magnesium glycine, and 0.5 parts thomaline. The preparation method was the same as in Example 2, thus obtaining a medium-dose hypoglycemic powder composition.

[0049] Example 4: Preparation of high-dose hypoglycemic composition powder

[0050] The following components were weighed according to their respective weight proportions: 70 parts burdock polysaccharide, 40 parts chitosan oligosaccharide (molecular weight 1500 Da), 15 parts chlorogenic acid, 12 parts epicatechin, 10 parts resveratrol, 8 parts ginsenoside Rd, 0.01 parts vitamin D, 0.1 parts vitamin B1, 0.1 parts vitamin B6, 0.002 parts vitamin B12, 2 parts magnesium glycine, and 0.5 parts thomaline. The preparation method was the same as in Example 2, thus obtaining a high-dose hypoglycemic powder composition.

[0051] Example 5: In vivo hypoglycemic activity experiment of the hypoglycemic composition

[0052] Experimental Animals and Grouping: Eighty SPF-grade male SD rats were randomly divided into a normal control group (NC, n=10) and a high-fat group (n=70) after one week of acclimatization. The high-fat group was fed a high-fat diet for 7 weeks, followed by intraperitoneal injection of streptozotocin (STZ) 40 mg / kg to establish a type 2 diabetes model. The model rats were then randomly divided into a model group, a positive control group (DMBG, metformin 200 mg / kg), an burdock polysaccharide monotherapy group (ALI, 300 mg / kg), a low-dose combination group (Com-L, given the composition of Example 2), a medium-dose combination group (Com-M, given the composition of Example 3), and a high-dose combination group (Com-H, given the composition of Example 4). The low, medium, and high-dose groups were calculated based on burdock polysaccharide levels of 100, 300, and 500 mg / kg, respectively, and approximately 175, 630, and 1125 mg / kg of the low, medium, and high-dose combinations were administered by gavage for 6 weeks.

[0053] After establishing the diabetic model, blood was collected from the tail of the eye the morning before drug treatment and 6 weeks after drug treatment, following a 12-hour fasting period with unlimited water intake. Fasting blood glucose (FBG) was measured using a glucometer. Glucose tolerance was then measured by oral gavage administration of 2 g / kg glucose (40% glucose solution), with blood glucose levels measured at 0, 30, 60, and 120 minutes. Line graphs were plotted, and the area under the blood glucose curve (AUC) was calculated. Serum fasting insulin (FINS) was measured using an ELISA kit. The homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISI) were then calculated using the following formulas: HOMA-IR = FBG × FINS / 22.5, ISI = 1 / (FBG × FINS). Blood was collected from the eyeballs by centrifugation. Serum levels of total cholesterol (TC), triglycerides (TG), and free fatty acids (FFA) were measured using a kit. The levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using an ELISA kit. After blood collection, pancreatic samples were collected, and the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in the pancreas were determined using a kit method.

[0054] result:

[0055] (1) Fasting blood glucose: After successfully establishing a diabetic rat model, the fasting blood glucose level of the diabetic rats was significantly increased (P<0.01). Compared with the model group, the fasting blood glucose level decreased to 16.45 mmol / L after administration of burdock polysaccharide alone (P<0.05), demonstrating the long-term basic blood glucose control ability of burdock polysaccharide. The low, medium, and high dose combination groups reduced the fasting blood glucose to 15.24, 13.34, and 12.90 mmol / L, respectively. In particular, the blood glucose lowering effect of the medium and high dose combination groups was significantly better than that of the burdock polysaccharide alone group. This excellent effect is attributed to the superposition of the long-term homeostasis provided by burdock polysaccharide in the combination and the rapid improvement of insulin sensitivity by components such as chitosan oligosaccharide. The difference between the medium and high dose groups was small. According to the dosage principle, the medium dose group was preferred.

[0056] Table 1: Effects of the composition on fasting blood glucose in diabetic rats

[0057]

[0058] Note: and ## are statistical significance markers. ## indicates that the difference was statistically significant compared with the normal control group (NC group) (P<0.01); ## indicates that the difference was statistically significant compared with the diabetes model group (Model group) (P<0.01); the sample size of each group was n=8.

[0059] (2) Glucose tolerance: see Figure 1 The experimental results showed that the use of burdock polysaccharide significantly improved glucose intolerance in diabetic rats, while the effect of the combined composition was even more significant. Specifically, the blood glucose levels in the medium- and high-dose groups 120 minutes after gavage were 15.41 mmol / L and 14.87 mmol / L, respectively, significantly lower than the 22.83 mmol / L in the model group. Figure 1 A, P<0.01), the area under the curve also decreased significantly ( Figure 1 B, P<0.01). The glucose tolerance effects of Com-M and Com-H were significantly better than those of the burdock polysaccharide-only group and the low-dose combination group. This is attributed to the synergistic effect between burdock polysaccharide, chitosan oligosaccharide, and other components, demonstrating the excellent postprandial blood glucose management ability of the combination. The rapid absorption and signal activation properties of chitosan oligosaccharide played a key role in this process; it can quickly respond to glycemic load, promote glucose uptake and utilization, and synergistically reduce postprandial blood glucose peaks and accelerate their decline, in conjunction with the sustained inhibition of glycosidase by burdock polysaccharide. The differences between the medium- and high-dose groups were small; based on dosage principles, the medium-dose group was preferred.

[0060] (3) Insulin Resistance: HOMA-IR and ISI have been widely used to guide the management of type 2 diabetes. Long-term high-sugar, high-fat feeding in rats leads to severe insulin resistance and a significant decrease in insulin sensitivity; however, treatment with the combination therapy can control blood glucose levels and significantly improve insulin disorders in rats. See also Figure 2 Compared with the model group, the Homa-IR index of the medium and high dose groups of the composition was significantly reduced ( Figure 2 A, P<0.01), decreased by 60.71% and 55.94%, respectively. The ISI values ​​in the medium and high dose groups of the composition were significantly increased ( Figure 2 B (P<0.01), compared with the model group, increased by 131.37% and 115.51%, respectively. The results show that the composition of the present invention, especially the medium and high dose compositions, has significant comprehensive effects in lowering blood sugar and improving insulin dysfunction, and its effect is better than that of the burdock polysaccharide alone group.

[0061] (4) Blood lipids: Due to insulin deficiency and persistent hyperglycemia, diabetes easily leads to lipid metabolism disorders, resulting in elevated blood lipid levels. See also Figure 3 Compared with the model group, the treatment groups all showed a significant reduction in blood lipid levels. In particular, the medium- and high-dose groups of the composition showed a significant reduction in serum total cholesterol (TC). Figure 3 A) Triglycerides (TG) Figure 3 B) Fatty acids (FFA, Figure 3C) levels decreased significantly (P<0.01), showing a significantly better effect than the burdock polysaccharide single-use group and the low-dose combination group.

[0062] (5) Inflammatory factors: Diabetes can lead to a decrease in the body's immunity, making it more susceptible to infections, which in turn can further exacerbate the condition of diabetes. See also Figure 4 Burdock polysaccharides can significantly reduce the key pro-inflammatory marker hs-CRP ( Figure 4 A), TNF-α ( Figure 4 B), IL-6 Figure 4 The serum level of C) was significantly lower (P<0.05), while the medium and high dose groups of the composition showed more significant effects (P<0.01).

[0063] (6) Oxidative stress: Prolonged hyperglycemia can induce oxidative stress, which in turn can further exacerbate damage to pancreatic β-cells and insulin resistance, leading to a further deterioration of diabetes. See also Figure 5 Compared with the normal group, the malondialdehyde (MDA) content in the pancreatic islets of rats in the model group was significantly increased (P<0.01), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were significantly decreased (P<0.01). The medium and high doses of the composition significantly inhibited the decrease in SOD and GSH-PX activities (P<0.01), thereby significantly reducing the production of malondialdehyde (MDA) (P<0.01).

[0064] In summary, the medium- and high-dose groups of the composition were significantly superior to the burdock polysaccharide-only group and the model group in improving HOMA-IR and ISI, reducing TC, TG, and FFA, inhibiting inflammatory factors such as hs-CRP, TNF-α, and IL-6, and increasing SOD and GSH-PX activity while reducing MDA levels. This further confirms the comprehensive advantages of the "long- and short-acting synergistic" strategy: short-acting components (such as chitosan oligosaccharide) immediately initiate cell protection and metabolic improvement programs; long-acting components (such as burdock polysaccharide) maintain the body's homeostasis during long-term treatment by continuously regulating the intestinal microecology and providing antioxidant precursors, thus jointly achieving deep and lasting intervention on pathways related to diabetes and its complications. The differences between the medium- and high-dose groups were small; based on dosage principles, the medium-dose group was preferred.

[0065] Example 6: Determination of the in vitro α-glucosidase inhibitory activity of the composition

[0066] α-Glucosidase can break down oligosaccharides and disaccharides into glucose for absorption by the body, making it an important drug target for diabetes treatment. The powder composition obtained in Example 3, i.e., the intermediate-dose group (Com-M) of the above composition, was selected and prepared into solutions of different concentrations using distilled water (concentrations of 0, 0.02, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28 mg / mL, respectively). An equal concentration of burdock polysaccharide (ALI) was also prepared. Acarbose was used as a positive control. Using the PNPG method, it was thoroughly mixed with 20 μL of 1 U / mL α-glucosidase and incubated in a 37°C water bath for 10 minutes. Subsequently, 20 μL of 5 mmol / L PNPG substrate was added and mixed well. After reacting at 37°C for 20 minutes, 0.2 mol / L Na₂CO₃ was added to terminate the reaction. The absorbance was measured at a wavelength of 405 nm, and the inhibition rate was calculated using the formula [1-(A sample-A blank) / (A control-A blank)]×100%. The IC50 value was obtained by fitting the dose-response curve.

[0067] See Figure 6 The results showed that the half-maximal inhibitory concentration (IC50) of burdock polysaccharide against α-glucosidase in vitro was 0.4651 mg / mL. However, the medium-dose composition of this invention exhibited stronger α-glucosidase inhibitory activity, with an IC50 value of 0.3189 mg / mL, which was superior to burdock polysaccharide (ALI) and acarbose alone. This indicates that other components in the composition, especially chitosan oligosaccharide, may synergistically enhance the inhibitory efficacy against peripheral glycosidases through allosteric regulation and other mechanisms. This reflects the in vitro activity of the composition and explains its mechanism of delaying carbohydrate absorption and assisting in long-term blood sugar control in vivo.

[0068] Example 7: Taste Evaluation Test

[0069] Thirty patients with type 2 diabetes were randomly divided into two groups, A and B, with 15 patients in each group. Group A took the composition without semaside (the semaside was removed from the formulation of Example 3, and the rest were the same), while Group B took the composition containing semaside prepared in Example 3. After the respective compositions were dissolved in warm water, the taste was evaluated using a visual analog scale (0 points for the most unacceptable taste, and 10 points for the best taste). The results showed that the average score for Group A was 4.1 ± 0.8 points, and the average score for Group B was 8.9 ± 1.6 points, indicating that semaside significantly improved the taste of the compositions and increased patient compliance.

[0070] The above description is merely an example and illustration of the structure of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described, or use similar methods to replace them, as long as they do not deviate from the inventive concept of the present invention, and all such modifications or additions should fall within the protection scope of the present invention.

Claims

1. A composition containing burdock polysaccharide for lowering blood glucose in patients with type 2 diabetes, characterized in that, Composed of active ingredients and excipients; The active ingredients include burdock polysaccharide, chitosan oligosaccharide, chlorogenic acid, epicatechin, resveratrol, and ginsenoside Rd; The excipients include vitamin D, vitamin B1, vitamin B6, vitamin B12, magnesium glycine, and sematriol.

2. The composition according to claim 1, characterized in that, The components, by weight, are as follows: burdock polysaccharide 30-70 parts; chitosan oligosaccharide 10-40 parts; chlorogenic acid 5-15 parts; epicatechin 3-12 parts; resveratrol 2-10 parts; ginsenoside Rd 1-8 parts; vitamin D 0.001-0.01 parts; vitamin B1 0.01-0.1 parts; vitamin B6 0.01-0.1 parts; vitamin B12 0.0001-0.002 parts; magnesium glycine 0.5-2 parts; sematriol 0.1-2 parts.

3. The composition according to claim 2, characterized in that, The components, by weight, are as follows: burdock polysaccharide 50 parts; chitosan oligosaccharide 25 parts; chlorogenic acid 10 parts; epicatechin 8 parts; resveratrol 6 parts; ginsenoside Rd 5 parts; vitamin D 0.005 parts; vitamin B1 0.05 parts; vitamin B6 0.05 parts; vitamin B12 0.0008 parts; magnesium glycine 1 part; 0.5 parts of sematriol protein.

4. The composition according to claim 1, characterized in that, The molecular weight of the chitosan oligosaccharide is 1000-2000 Da.

5. The composition according to claim 4, characterized in that, The molecular weight of the chitosan oligosaccharide is 1500 Da.

6. The composition according to claim 1, characterized in that, The burdock polysaccharide was prepared by the following method: S1. Take fresh burdock root, wash it, blanch it in hot water at 90-100℃ for 3-8 minutes, peel it, cut it into sections, press it, and collect the juice and burdock residue separately. S2. Add hot water at 50-80℃ to the burdock residue at a solid-liquid ratio of 1:10 to 1:30 (g / mL), soak for 20-40 minutes, and press again while hot. Repeat 1-2 times. S3. Combine all extracts, centrifuge and filter, concentrate the filtrate to 1 / 5 to 1 / 10 of the original volume, add 2 to 4 times the volume of 95% ethanol, let stand at 4°C for 12 to 18 hours, and centrifuge to collect the precipitate. S4. Redissolve the precipitate in water, add 0.5% to 1.5% (w / v) of papain, and enzymatically hydrolyze at pH 6.0 to 6.5 and 55°C for 3 hours. Boil for 10 minutes to inactivate the enzyme, centrifuge to remove the precipitate, and treat the supernatant with Sevage reagent by shaking 1 to 2 times. Then decolorize with D101 macroporous adsorption resin. S5. Dilute the decolorized polysaccharide solution to a concentration of 5-10 g / L, and concentrate it to 1 / 3-1 / 5 of the original volume using an ultrafiltration membrane with a molecular weight cutoff of 1000 Da. Then add an equal volume of ultrapure water for washing and filtration, repeating 3-4 times. Collect the retentate. After concentration under reduced pressure, dry the retentate to obtain burdock polysaccharide.

7. The composition according to claim 1, characterized in that, The composition is in the form of powder or tablets.

8. A method for preparing the composition according to any one of claims 1 to 7, characterized in that, Includes the following steps: (1) Weigh out the following ingredients by weight: burdock polysaccharide, chitosan oligosaccharide, chlorogenic acid, epicatechin, resveratrol, ginsenoside Rd, vitamin D, vitamin B1, vitamin B6, vitamin B12, magnesium glycine and sematriol; (2) Crush each raw material and pass it through an 80-120 mesh sieve; (3) Place the pulverized raw materials in a mixer and mix thoroughly until homogeneous; (4) Sterilize the mixture and package it according to specifications to obtain powder; or sterilize the mixture and compress it into tablets to obtain tablets.

9. The use of the composition according to any one of claims 1 to 7 in the preparation of a pharmaceutical or functional food for lowering blood glucose in patients with type 2 diabetes.

10. The application according to claim 9, characterized in that, The application is the use of the composition in the preparation of pharmaceuticals or functional foods having at least one of the following uses: lowering fasting blood glucose, improving insulin resistance, improving glucose tolerance, lowering blood lipids, lowering inflammatory factor levels, and reducing oxidative stress damage.

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