A composite composition for regulating glucose and lipid metabolism in diabetes and its application.

Abstract

This invention provides a compound composition for regulating glucose and lipid metabolism in diabetes and its application, belonging to the fields of medicine, food, and health products. The composition comprises an enzymatically hydrolyzed extract of Polygonatum sibiricum, a compound extract of traditional Chinese medicine including Astragalus membranaceus, ginseng, mulberry leaf, cinnamon, white kidney bean, and bitter melon, probiotics including Lactobacillus rhamnosus and Bifidobacterium bifidum B11, hydrolyzed collagen peptides, and tagatose, scientifically formulated according to the principles of traditional Chinese medicine. This composition can comprehensively regulate the multidimensional pathological characteristics of diabetes, such as glucose and lipid metabolism disorders, chronic inflammation, and weight loss, exerting a synergistic effect. Its hypoglycemic, lipid-regulating, anti-inflammatory, and weight-recovery-promoting effects are significantly better than the sum of the individual effects of each component. It can also significantly improve serum free fatty acid, fasting insulin, and inflammatory factor levels, providing a new approach for developing safe and effective adjunctive treatment products for diabetes.

Description

Technical Field

[0001] This invention belongs to the fields of medicine, food or health products technology, and specifically relates to a composite composition for regulating glucose and lipid metabolism in diabetes and its application. Background Technology

[0002] Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disease worldwide. Its core pathological features include insulin resistance and dyslipidemia, often accompanied by chronic low-grade inflammation and oxidative stress. Long-term metabolic imbalance can lead to various serious complications such as hepatic steatosis and cardiovascular disease, severely impacting patients' quality of life and prognosis. According to the latest data from the International Diabetes Federation (IDF), the number of T2DM patients worldwide continues to rise, highlighting the serious challenges in prevention and treatment.

[0003] Currently, commonly used clinical hypoglycemic drugs such as metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors, while effective in controlling blood sugar, still have limitations. For example, long-term use can easily cause side effects such as gastrointestinal discomfort and kidney damage, and their effectiveness in improving accompanying metabolic problems such as dyslipidemia and chronic inflammation is limited. Therefore, finding adjunctive intervention strategies that can intervene in glucose and lipid metabolism disorders through multiple pathways and targets with good safety has become one of the important directions of current research. Summary of the Invention

[0004] In view of the technical problems of existing hypoglycemic drugs having obvious side effects, insufficient improvement on blood lipid disorders and inflammatory states, and limited regulatory effects of single natural ingredients, the purpose of this invention is to provide a compound composition for regulating glucose and lipid metabolism in diabetes and its application.

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

[0006] This invention provides a composite composition prepared from the following raw materials in parts by weight: 1-3 parts of Polygonatum odoratum enzymatic hydrolysis extract, 1-3 parts of traditional Chinese medicine compound extract, 1-3 parts of Lactobacillus rhamnosus JYLR-005, 0.1-0.5 parts of Bifidobacterium bifidum B11, 0.1-1 parts of hydrolyzed collagen peptide, and 1-3 parts of tagatose; the traditional Chinese medicine compound extract is obtained by compounding and extracting white kidney bean, mulberry leaf, bitter melon, cinnamon, astragalus, and ginseng in a weight ratio of (2-4):(0.5-2):(0.5-2):(0.5-2):(0.5-2):(0.5-2).

[0007] Furthermore, the composite composition is prepared from the following raw materials in parts by weight: 2 parts of Polygonatum sibiricum enzymatic hydrolysis extract, 2 parts of traditional Chinese medicine compound extract, 2 parts of Lactobacillus rhamnosus JYLR-005, 0.2 parts of Bifidobacterium bifidum B11, 0.5 parts of hydrolyzed collagen peptide, and 2 parts of tagatose; in the traditional Chinese medicine compound extract, the weight ratio of white kidney bean, mulberry leaf, bitter melon, cinnamon, astragalus, and ginseng is 3:1:1:1:1:1.

[0008] Furthermore, the preparation of the enzymatic hydrolysis extract of Polygonatum includes the following steps: after pretreatment of Polygonatum medicinal material, enzymatic hydrolysis is performed using a compound enzyme, and the hydrolysate is obtained after enzyme inactivation, filtration, concentration and drying; the compound enzyme includes cellulase and protease.

[0009] Furthermore, the preparation of the enzymatic hydrolysis extract of Polygonatum includes the following steps:

[0010] (1) Remove impurities and fibrous roots from fresh Polygonatum, wash and air dry for 12-36 hours, place in an oven at 30-50℃ and dry for 12-36 hours to achieve a moisture content of 25%-40%; take out and cut into 5-10mm thick slices, then dry in an oven at 40℃ for 12-36 hours to achieve a moisture content of 15%-24%; place the dried Polygonatum slices in a steaming container and steam for 4-8 hours, then take them out; dry with hot air at 55-80℃ for 10-20 hours to achieve a moisture content of 12%-15%, thus obtaining Polygonatum that has been steamed and dried once; repeat the above operation four times to obtain Polygonatum that has been steamed and dried five times; place the Polygonatum that has been steamed and dried five times in a steaming container and steam for 4-8 hours, then take it out; dry with hot air at 70-80℃ to achieve a moisture content of 7%, thus obtaining Polygonatum that has been steamed and dried six times. Add 10 times the volume (v / w) of water, adjust the pH to 5 at 50℃, add 4% (w / w) of enzyme for preparing Polygonatum (cellulase: pectinase = 1:1), and react for 3 hours;

[0011] (2) At 45℃, the pH value was kept constant to 8.5, and 4% (w / w) alkaline protease for preparing Polygonatum was added, and the reaction was carried out for 3 hours.

[0012] (3) At 30-45℃, add 4% (w / w) of neutral protease for preparing Polygonatum sibiricum and react for 3 hours;

[0013] (4) The obtained enzymatic hydrolysate was heated to 90°C and kept at a constant temperature for half an hour to inactivate the enzyme. The solution was then filtered. The filtrate was concentrated under reduced pressure at a vacuum of 0.08 MPa and a temperature of 50°C, and finally freeze-dried to obtain the enzymatic hydrolysate of Polygonatum odoratum.

[0014] Furthermore, the extraction method of the traditional Chinese medicine compound extract is water extraction and / or alcohol extraction, and the yield of the extract is 5~15 g of medicinal material / g of extract.

[0015] Furthermore, the extraction method of the traditional Chinese medicine compound extract is water extraction, and the yield of the extract is 10 g of medicinal material / g of extract.

[0016] Furthermore, the viable count of the *Lactobacillus rhamnosus* JYLR-005 is ≥10 billion CFU / g; the viable count of the *Bifidobacterium bifidum* B11 is ≥100 billion CFU / g; and the molecular weight of the hydrolyzed collagen peptide is 2000-3000 Da.

[0017] Furthermore, the purity of the hydrolyzed collagen peptides is ≥95%; and the purity of the tagatose is ≥99%.

[0018] The present invention also provides the use of the above-mentioned composite composition in the preparation of health foods that help maintain healthy blood sugar levels, help maintain healthy blood lipid levels, and help regulate gut microbiota.

[0019] The present invention also provides the use of the above-described composite composition in the preparation of medicaments for the prevention and / or treatment of diabetes.

[0020] Furthermore, the diabetes is type II diabetes.

[0021] Furthermore, the drug is a drug that lowers blood sugar, reduces inflammation, and regulates blood lipids and weight.

[0022] The formula for the composite composition provided by this invention is as follows:

[0023] 1. Overall Formula Characterization: From the perspective of Traditional Chinese Medicine, the compound composition of this invention belongs to the category of "tonifying both Qi and Yin, clearing heat and moistening dryness, and supplementing with turbidity-resolving agents," targeting the core pathogenesis of diabetes mellitus characterized by "deficiency of both Qi and Yin, accompanied by dryness, heat, and dampness." In modern medicine, the compound composition of this invention is a dietary supplement that synergistically regulates blood sugar through multiple pathways. Its mechanism of action includes inhibiting carbohydrate absorption, improving insulin sensitivity, protecting pancreatic β-cells, and regulating intestinal flora.

[0024] 2. Explanation based on Traditional Chinese Medicine Theory: Based on the principles of traditional Chinese medicine (TCM) formula composition (principal, assistant, adjuvant, and guide), the components of the composite composition of this invention are analyzed:

[0025] (1) Principal drug:

[0026] Astragalus extract: sweet and slightly warm, it enters the spleen and lung meridians. It tonifies qi and raises yang, generates fluids and nourishes blood. It is an essential medicine for tonifying qi. It can strengthen the spleen and distribute fluids, fundamentally improving the pathogenesis of spleen deficiency and impaired function, and leakage of essence.

[0027] Ginseng extract: sweet, slightly bitter, slightly warm, enters the spleen, lung, heart and kidney meridians. It greatly replenishes vital energy, invigorates the spleen and lungs, and promotes the production of body fluids and quenches thirst. Together with astragalus, it targets the root cause of deficiency of both qi and yin, and together they are the commanders of the formula.

[0028] (2) Assistant medicine:

[0029] Polygonatum rhizome enzymatic hydrolysis extract: sweet, neutral, enters the spleen, lung and kidney meridians, replenishes qi and nourishes yin, strengthens the spleen, moistens the lungs and benefits the kidneys. After enzymatic hydrolysis, it is more easily absorbed, enhancing its function of "replenishing all deficiencies and filling the essence", and assisting the principal medicine in nourishing yin and moistening dryness.

[0030] Mulberry leaf extract: sweet, bitter, cold, enters the lung and liver meridians, clears the lungs and moistens dryness, calms the liver and improves eyesight. It can clear dryness and heat in the lungs to relieve thirst. Its purging effect is similar to the effect of modern glycosidase inhibition.

[0031] Cinnamon extract: pungent, sweet, and very hot in nature, it enters the kidney, spleen, heart, and liver meridians. It tonifies fire and assists yang, guides fire back to its source, and while tonifying qi and yin, it also warms yang and transforms qi, promotes the distribution of body fluids, and guides deficient fire back to its origin.

[0032] (3) Adjuvant:

[0033] White kidney bean extract: sweet and neutral in nature, it enters the spleen and stomach meridians and can strengthen the spleen and harmonize the middle jiao; its inhibitory effect on α-amylase is regarded by traditional Chinese medicine as "the source of dietary restraint" and reduces the burden on the spleen and stomach.

[0034] Bitter melon extract: bitter, cold, enters the heart, spleen and lung meridians, clears heat and detoxifies, uses bitterness to purge, clears dryness and heat and toxic fire in the body (corresponding to chronic inflammatory state).

[0035] Lactobacillus rhamnosus and Bifidobacterium bifidum: Based on the TCM theory of "spleen and stomach", probiotics can be regarded as regulating the "microscopic spleen and stomach", which can strengthen the spleen and stomach, resolve dampness and turbidity, improve intestinal function, and remove pathological products of dampness and turbidity.

[0036] (4) To administer medicine

[0037] Hydrolyzed collagen peptides: belonging to the category of "products with blood and flesh", they can replenish essence and marrow, nourish yin and blood. They have the potential to improve skin dryness and slow wound healing caused by prolonged thirst and depletion of essence and blood, and play a role in harmonizing and nourishing.

[0038] Tagase: By inhibiting intestinal disaccharidase and reducing liver glycogenolysis, it directly reduces glucose absorption and production, playing a guiding role in assisting blood sugar reduction in the formula.

[0039] 3. Synergistic Pathway of Modern Pharmacological Action: The composite composition of this invention exerts its effect through the following multi-stage synergistic mechanism:

[0040] (1) Inhibit sugar absorption at the source: White kidney bean extract inhibits α-amylase, reducing carbohydrate decomposition and absorption.

[0041] (2) Improve glucose metabolism and insulin sensitivity: Mulberry leaf and bitter melon extracts improve insulin sensitivity and promote glucose utilization; cinnamon extract mimics insulin activity and enhances glucose metabolism.

[0042] (3) Protecting pancreatic islet function and body repair: Astragalus and ginseng extracts protect pancreatic β cells, fight fatigue, and enhance overall function; Polygonatum and hydrolyzed collagen peptides provide nutritional support, anti-oxidation, and promote tissue repair.

[0043] (4) Regulating intestinal microecology: Probiotics improve intestinal barrier function, reduce endotoxemia and chronic inflammation, and produce beneficial short-chain fatty acids, thereby improving insulin resistance from an environmental perspective.

[0044] The composite composition of this invention embodies a precise integration of traditional Chinese and Western medicine thinking: it strictly follows the treatment principle of "tonifying qi and nourishing yin to treat the root cause, clearing heat and moistening dryness to treat the symptoms, and warming yang and transforming qi to assist its function", with a rigorous structure and clear distinction between the principal, assistant, adjuvant and guide components; it intervenes at multiple targets from four key aspects: "reducing sugar absorption, improving insulin sensitivity, protecting pancreatic islet cells, and regulating intestinal flora", with each component working synergistically to achieve comprehensive blood glucose management.

[0045] The composite composition provided by this invention achieves the following beneficial effects:

[0046] (1) Significant synergistic effect, comprehensive improvement of metabolic disorders in multiple dimensions: The core advantage of this invention lies in the synergistic effect of "1+1>2" produced by the scientific combination of its components. Through verification in a T2DM rat model induced by high-fat diet combined with STZ, the complete compound formula of this invention (Group E) was significantly better than the intervention effects of the plant extract combination (Group XA) and the probiotic-functional excipient combination (Group XB) in terms of blood sugar reduction rate (57.20%), weight recovery rate (25.2%), and improvement of key metabolic and inflammatory indicators such as serum FFA, FINS, IL-6, and TNF-α. It even exceeded the theoretical superposition improvement rate of the two groups (e.g., the improvement rate of FINS exceeded the theoretical value by 19.6%). This proves that this invention is not a simple accumulation of components, but achieves synergistic coverage and efficient regulation of the core pathological links of T2DM through the complementarity and linkage of multiple components and multiple targets (such as inhibiting sugar absorption, promoting insulin secretion, regulating intestinal flora, and inhibiting inflammation).

[0047] (2) The four-in-one effect of "lowering blood sugar, regulating lipids, anti-inflammation, and maintaining weight" breaks through the limitations of existing drugs: Compared with first-line hypoglycemic drugs such as metformin, which mainly focus on controlling blood sugar and may be accompanied by gastrointestinal side effects and have limited improvement on lipid metabolism and inflammation, the compound formula of this invention achieves comprehensive intervention. While effectively lowering blood sugar, it can significantly improve lipid metabolism (reduce FFA), inhibit chronic low-grade inflammation (reduce IL-6 and TNF-α), and effectively reverse the pathological weight loss trend in diabetic model animals, promoting nutrient absorption and metabolic recovery. This "four-in-one synergistic" mode of action is more in line with the complex clinical reality of T2DM patients who often have glucose and lipid metabolism disorders, chronic inflammation, and nutritional imbalance, providing a more comprehensive adjuvant treatment strategy for the prevention and control of complications.

[0048] (3) Clear Mechanism, Integrating Modern Nutrition and Traditional Chinese Medicine Theories: The formula design of this invention combines modern scientific basis with traditional Chinese medicine wisdom. On the one hand, the functions of each component are clear: Polygonatum and the compound Chinese medicine play a core role in lowering blood sugar and regulating lipids; probiotics regulate the intestinal microecology and improve the function of the "gut-pancreatic axis"; hydrolyzed collagen peptides provide nutritional support; and tagatose assists in blood sugar control. On the other hand, the formula follows the principle of "principal, assistant, adjuvant and guide" in traditional Chinese medicine for overall compatibility, emphasizing "nourishing yin and tonifying yang" while "lowering blood sugar", and promoting the overall recovery of bodily functions through "spleen governing transportation and transformation", reflecting the concept of "treating both the symptoms and the root cause", and providing an innovative theoretical explanation for the mechanism of action.

[0049] (4) Safe raw materials, strong dosage form adaptability, and broad development prospects: All ingredients in the formula are high-purity food or pharmaceutical grade raw materials (such as Polygonatum extract ≥90%, tagatose ≥99%), and the probiotics use high viable bacteria strains (≥10 billion CFU / g), ensuring high safety and suitability for long-term consumption. Its dosage form can be flexibly developed into oral preparations such as powders and capsules, with good process adaptability. Animal experiments have shown significant effects in the low-dose group, and the high-dose group did not increase the metabolic burden, providing a broad safety window for subsequent clinical dosage exploration. In addition, its mechanism of action of regulating intestinal flora through probiotics makes this product not only suitable for the adjunctive treatment of T2DM patients, but also has the potential to be extended to the prediabetic population for preventive intervention, with broad market application prospects.

[0050] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0051] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following embodiments. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0052] Figure 1 The change in blood glucose in rats. Detailed Implementation

[0053] The raw materials and equipment used in this invention are all known products, obtained by purchasing commercially available products.

[0054] In the formulation of the specific embodiments of the present invention, "part" refers to parts by weight, and 1 part is 1g.

[0055] Example 1: Preparation of the composite composition of the present invention

[0056] 1. The formulation of the compound composition (by weight): 2 parts of Polygonatum odoratum enzymatic hydrolysis extract, 2 parts of traditional Chinese medicine compound extract, 2 parts of Lactobacillus rhamnosus JYLR-005 (live count ≥10 billion CFU / g), 0.2 parts of Bifidobacterium bifidum B11 (live count ≥100 billion CFU / g), 0.5 parts of hydrolyzed collagen peptide (molecular weight 2000-3000 Da, purity ≥95%), and 2 parts of tagatose (purity ≥99%).

[0057] 2. Preparation methods of key raw materials

[0058] (1) Preparation of Polygonatum enzymatic hydrolysis extract: According to the processing method of steamed Polygonatum in patent ZL201810049671.5, Polygonatum was prepared by steaming and processing six times. The specific steps are as follows: (1) Remove impurities and fibrous roots from fresh Polygonatum, wash and air dry for 12-36 hours, place it in an oven at 30-50℃ and dry for 12-36 hours to make its moisture content reach 25%-40%; take it out and cut it into thick slices of 5-10 mm, and then dry it in an oven at 40℃ for 12-36 hours. The dried Polygonatum sibiricum is steamed for 4-8 hours to achieve a moisture content of 15%-24%. The dried slices are then placed in a steaming container and steamed for 4-8 hours. After steaming, they are dried in hot air at 55-80℃ for 10-20 hours to achieve a moisture content of 12%-15%, thus obtaining a single-steamed and single-dried Polygonatum sibiricum. This process is repeated four times to obtain a five-steamed and five-dried Polygonatum sibiricum. The five-steamed and five-dried Polygonatum sibiricum is then placed in a steaming container and steamed for 4-8 hours. After steaming, it is dried in hot air at 70-80℃ to achieve a moisture content of 7%, thus obtaining a six-steamed and six-dried Polygonatum sibiricum. Add 10 times the volume (v / w) of water, adjust the pH to 5 at 50°C, add 4% (w / w) of enzyme for preparing Polygonatum (cellulase: pectinase = 1:1), and react for 3 hours; (2) at 45°C, keep the pH constant to 8.5, add 4% (w / w) of alkaline protease for preparing Polygonatum, and react for 3 hours; (3) at 30-45°C, add 4% (w / w) of neutral protease for preparing Polygonatum, and react for 3 hours; (4) heat the obtained enzymatic hydrolysate to 90°C, keep it at a constant temperature for half an hour to inactivate the enzyme, and filter; concentrate the filtrate under reduced pressure at a vacuum degree of 0.08 MPa and a temperature of 50°C, and finally freeze dry to obtain Polygonatum enzymatic hydrolysate with a polysaccharide content of 50%.

[0059] (2) Preparation of compound extract of traditional Chinese medicine: weigh the medicinal materials according to the weight ratio of white kidney bean: mulberry leaf: bitter melon: cinnamon: astragalus: ginseng = 3:1:1:1:1:1, add water 10 times the total weight of the medicinal materials and extract twice, each time for 1 hour, concentrate, spray dry to obtain compound extract of traditional Chinese medicine (containing 10 grams of medicinal materials / gram of extract).

[0060] Other reagents: Lactobacillus rhamnosus JYLR-005 (viable count ≥ 10 billion CFU / g, purchased from Shandong Zhongke Jiayi Biotechnology Co., Ltd.), Bifidobacterium bifidum B11 (viable count ≥ 100 billion CFU / g, purchased from Hebei Yirang Biotechnology Co., Ltd.); hydrolyzed collagen peptide (molecular weight 2000-3000 Da, purity ≥ 95%), purchased from Zhejiang Nuo Derivative Technology Co., Ltd.; tagatose (purity ≥ 99%), purchased from Henan Yihengyuan Biotechnology Co., Ltd.

[0061] Weigh each component according to the above ratio and mix them evenly to obtain the composite composition of the present invention.

[0062] Example 2. Effect of the composite composition of the present invention on glucose and lipid metabolism in diabetes

[0063] In this example, type II diabetic rats induced by high-fat feeding combined with streptozotocin (STZ) were used as a model to verify the improvement effect of the composite composition of the present invention on glucose and lipid metabolism and related inflammatory indexes in diabetic model rats.

[0064] I. Experimental materials

[0065] 1. Experimental instruments [[ID=I7]]<U

[0066] Table 1 Experimental instrument table

[0067]

[0068] 2. Experimental animals

[0069] 84 SPF-grade SD male rats at 8 weeks of age, weighing 200 ± 20 g, were purchased from Chengdu Dashuo Experimental Animal Co., Ltd., license number: SCXK (Chuan) 2020-030. The feeding temperature was 20-25 °C, the humidity was 40%-60%, and the light and dark alternated for 12 h. Under the light and dark alternating light mode, they were fed and drank water freely. After 7 days of adaptive feeding, the experiment was carried out.

[0070] 3. Experimental reagents <U

[0071] Enzyme-linked immunosorbent assay (Elisa) kits: insulin (INS), tumor necrosis factor α (TNF-α), glutathione peroxidase (GSH-Px), interleukin 6 (IL-6), catalase (CAT), malondialdehyde (MDA), total superoxide dismutase (SOD) assay kits, provided by Wuhan Enzyme-Free Biology Co., Ltd.

[0072] Modeling reagents: streptozotocin (STZ) and sodium citrate were purchased from Beijing Solarbio Science & Technology Co., Ltd.; high-sugar and high-fat feed (containing 20% ​​sucrose, 10% lard, 2% cholesterol, and 0.5% sodium cholate, supplemented to 100% of the basic feed) was customized by Beijing Huafukang Biotechnology Co., Ltd.

[0073] Positive drug: Metformin (purity ≥98%), purchased from Sigma-Aldrich.

[0074] II. Experimental Methods

[0075] 1. Establishment of a type II diabetic rat model

[0076] After 7 days of acclimatization, 12 rats were selected as the control group and fed a basal diet. The remaining rats were induced using a high-fat diet combined with streptozotocin (STZ): they were fed a high-sugar, high-fat diet for 8 weeks, fasted for 12 hours but allowed free water, and then injected intraperitoneally with 1% STZ sodium citrate buffer at a dose of 30 mg / kg, freshly prepared and used immediately. The control group rats were injected intraperitoneally with an equal volume of 1% sodium citrate buffer. Fasting blood glucose levels were measured 3 days later; a blood glucose level ≥ 11.1 mmol / L indicated successful model establishment.

[0077] 2. Grouping and Dosing

[0078] Rats that successfully developed the model were divided into 7 groups: B (model group), C (positive group), D (low-dose treatment group), E (high-dose treatment group), XA (Polygonatum sibiricum enzymatic hydrolysis extract + traditional Chinese medicine compound extract group), and XB (Lactobacillus rhamnosus + Bifidobacterium bifidum B11 + hydrolyzed collagen peptide + tagatose group), with 12 rats in each group. The rats were treated for 24 days, and blood glucose was measured every 2 days. The treatment conditions are shown in Table 2.

[0079] In this study, groups D and E were given different doses of the composite composition of the present invention obtained in Example 1. Group XA was given a composition obtained by mixing Polygonatum hydrolysate and traditional Chinese medicine compound extract according to a formula (by weight): 2 parts Polygonatum hydrolysate and 2 parts traditional Chinese medicine compound extract. Group XB was given a composition obtained by mixing Lactobacillus rhamnosus, Bifidobacterium bifidum B11, hydrolyzed collagen peptides, and tagatose according to a formula (by weight): 2 parts Lactobacillus rhamnosus, 0.2 parts Bifidobacterium bifidum B11, 0.5 parts hydrolyzed collagen peptides, and 2 parts tagatose. All compositions were administered in the form of a distilled water solution.

[0080] The clinically equivalent dose is 15 g of Polygonatum sibiricum slices daily (based on a 60 kg adult). Converted using the body surface area method, the equivalent dose for rats is approximately 1.55 g / kg. The experiment included two dose groups: a low dose of 33 mg / kg and a high dose of 67 mg / kg.

[0081] Table 2 Administration conditions

[0082]

[0083] 3. Observation Indicators

[0084] (1) General survival status: The rats' mental state, hair quality, abnormal excrement and food and water intake were observed and measured accurately to assess their overall survival status;

[0085] (2) Blood glucose monitoring: The tail vein blood collection method was used to detect fasting blood glucose in rats at fixed time points every 2 hours and the blood glucose meter was used for analysis to dynamically monitor the establishment of hyperglycemia after modeling and the blood glucose change trend of each drug group in different intervention periods.

[0086] (3) Weight measurement: All rats were weighed and recorded using a precision electronic balance at fixed time points each week before modeling (as baseline), after modeling (to verify successful modeling), and after drug intervention;

[0087] (4) Serum marker detection: After the last administration and fasting for 12 hours, rats were anesthetized by intraperitoneal injection of sodium pentobarbital, and blood was collected from the abdominal aorta. The collected whole blood samples were allowed to stand, centrifuged to separate serum, and stored in an ultra-low temperature freezer at -80℃ for later use. Enzyme-linked immunosorbent assay (ELISA) was used to quantitatively detect the levels of free fatty acids (FFA), fasting insulin (FINS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum to evaluate the effects of drug intervention on the metabolic and inflammatory status of diabetic rats.

[0088] 4. Statistical Analysis

[0089] SPSS statistical software was used for data analysis. One-way ANOVA was used for data between multiple groups, and LSD test was used for pairwise comparisons between groups. # indicates a comparison with the model group, and # indicates a comparison with the blank group. Analysis results. P A value <0.05 indicates a statistically significant difference. Plotting was performed using ORIGIN software.

[0090] III. Experimental Results

[0091] 1. General condition and blood glucose changes

[0092] Compared with the control group, the rats in the model group were enlarged, lethargic, had rough fur often accompanied by urine stains, and exhibited significantly increased food and water intake, all typical symptoms of diabetes. Symptoms improved to varying degrees in all treatment groups.

[0093] Blood glucose monitoring results showed ( Figure 1Compared with the model group, the blood glucose levels in the positive group (metformin), low-dose group, high-dose group, XA group, and XB group were significantly reduced. Among them, the blood glucose reduction rate in the positive group was the fastest, followed by the high-dose group of the compound combination (Group E), and the blood glucose reduction effect was stable and long-lasting. The blood glucose reduction in the XA group and XB group was slower, and the blood glucose reduction rate of intervention alone was low (blood glucose reduction rate = (blood glucose after modeling - blood glucose 24 days after administration) / blood glucose after modeling × 100%), and the combined effect of the two was significantly less than that of the E group (blood glucose reduction rate of E group = 57.20%; blood glucose reduction rate of XA group = 27.40%; blood glucose reduction rate of XB group = 23.90%).

[0094] 2. Weight changes

[0095] Table 3 Changes in rat body weight

[0096]

[0097] Note: # Compared with the control group, P < 0.05; ## Compared with the control group, P < 0.01; Compared with the model group, P < 0.05; Compared with the model group, P < 0.01, the same applies below.

[0098] Before modeling, the baseline weight of rats in the blank group (A), model group (B), and each drug-treated group (C, D, E, XA, XB) was consistent (approximately 280-282g). After modeling, the weight of rats in the model group and each drug-treated group decreased significantly (P < 0.05 compared to the blank group), while the weight of the blank group increased slightly, indicating successful model establishment. In subsequent observations, the weight of the blank group continued to increase steadily and was significantly higher than that of the model group at all time points (P < 0.01), while the weight of the model group did not increase significantly throughout the process, and all drug-treated groups showed a trend of weight recovery. Groups C and E showed better weight recovery (P < 0.01 compared to the model group from the second week onwards), while groups D, XA, and XB showed relatively milder recovery (P < 0.05 compared to the model group at some time points). The highest weight recovery rate after 4 weeks of treatment was in group C (27.1%), followed by groups XA (12.4%) and XB (11.0%). Group E showed a weight recovery rate and magnitude close to the positive group, while groups XA and XB showed weaker weight recovery. Furthermore, the theoretical recovery effect of the combined treatment was lower than the actual recovery effect in group E. This indicates that the combined use of Polygonatum sibiricum enzymatic extract + traditional Chinese medicine compound extract with Lactobacillus rhamnosus + Bifidobacterium bifidum B11 + hydrolyzed collagen peptides + tagatose is more effective than either treatment alone.

[0099] 3. Serum marker analysis

[0100] Table 4 Effects on FFA, FINS, L-6, and TNF-α ( (±s, n=10)

[0101]

[0102] Note: Improvement rate calculation standard: FFA / IL-6 / TNF-a improvement rate = (model group index value - intervention group index value) / model group index value x 100% (the higher the value, the better the improvement effect); FINS improvement rate = (intervention group index value - model group index value) / model group index value x 100% (the higher the value, the better the improvement effect); Compared with the model group, P<0.05. Compared with the model group, P<0.01.

[0103] Four weeks after administration, the serum levels of FFA, IL-6, and TNF-α in the model group were significantly increased, while the level of FINS was significantly decreased, indicating that diabetic rats had significant glucose and lipid metabolism disorders and chronic inflammatory responses. All intervention groups improved the above-mentioned abnormal indicators to varying degrees. Among them, the high-dose compound formula group (Group E) showed the best effect. Its improvement rates of FFA (31.0%), FINS (53.9%), IL-6 (6.2%), and TNF-α (17.7%) were significantly higher than the sum of the effects of the individual interventions of Group XA and Group XB (theoretical improvement rates of 27.7% for FFA, 34.3% for FINS, 5.1% for IL-6, and 15.9% for TNF-α). Moreover, the actual measured values ​​of each indicator in Group E were closer to the normal levels of the blank group, which clearly confirmed that the components in the compound formula did not simply have a superposition effect, but rather synergistically regulated glucose and lipid metabolism, restored pancreatic secretory function, and inhibited chronic inflammation more efficiently through a synergistic mechanism. This was significantly better than the superposition effect of single component combinations, fully demonstrating the scientific nature and synergistic advantages of the formula.

[0104] In summary, this invention provides a compound composition for regulating glucose and lipid metabolism in diabetic rats and its application. Using a high-fat diet combined with streptozotocin-induced type 2 diabetic rat model, this invention systematically evaluated the regulatory effects of a compound formulation composed of enzymatically hydrolyzed extract of Polygonatum sibiricum, extracts of traditional Chinese medicine, probiotics (Lactobacillus rhamnosus and Bifidobacterium bifidum B11), hydrolyzed collagen peptides, and tagatose. The results showed that this compound formulation exhibited a significantly superior synergistic effect compared to the individual interventions or theoretical superposition of the components in improving glucose and lipid metabolism, promoting weight recovery, and inhibiting chronic inflammation. Specifically, the high-dose compound intervention group achieved a 57.20% reduction in blood glucose and a 25.2% weight recovery rate, and significantly improved serum free fatty acid, fasting insulin, and inflammatory factor levels. Its overall effect was close to that of the positive control drug metformin, with good safety. Mechanistically, this formulation, through multi-target synergy of "natural active ingredients - probiotics - functional excipients," covers multiple key pathological links such as hypoglycemia, lipid regulation, anti-inflammation, improvement of insulin resistance, and regulation of intestinal microecology. All components of this composite system are high-purity raw materials of food or pharmaceutical grade, with strong process adaptability, making it suitable for development into oral formulations. It not only provides experimental evidence and potential candidate solutions for multidimensional adjuvant treatment of type II diabetes, but also provides the possibility of extending from treatment to prevention and treatment, and has good prospects for transformation and application.

Claims

1. A composite composition, characterized in that, The composite composition is prepared from the following raw materials in parts by weight: 1-3 parts of Polygonatum odoratum enzymatic hydrolysis extract, 1-3 parts of traditional Chinese medicine compound extract, 1-3 parts of Lactobacillus rhamnosus JYLR-005, 0.1-0.5 parts of Bifidobacterium bifidum B11, 0.1-1 parts of hydrolyzed collagen peptide, and 1-3 parts of tagatose; the traditional Chinese medicine compound extract is obtained by compounding and extracting white kidney bean, mulberry leaf, bitter melon, cinnamon, astragalus and ginseng in a weight ratio of (2-4):(0.5-2):(0.5-2):(0.5-2):(0.5-2):(0.5-2).

2. The composite composition according to claim 1, characterized in that, The composite composition is prepared from the following raw materials in parts by weight: 2 parts of Polygonatum sibiricum enzymatic hydrolysis extract, 2 parts of traditional Chinese medicine compound extract, 2 parts of Lactobacillus rhamnosus JYLR-005, 0.2 parts of Bifidobacterium bifidum B11, 0.5 parts of hydrolyzed collagen peptide, and 2 parts of tagatose; in the traditional Chinese medicine compound extract, the weight ratio of white kidney bean, mulberry leaf, bitter melon, cinnamon, astragalus, and ginseng is 3:1:1:1:1:

1.

3. The composite composition according to claim 1, characterized in that, The preparation of the enzymatic hydrolysis extract of Polygonatum includes the following steps: after pretreatment of Polygonatum medicinal material, enzymatic hydrolysis is performed using a compound enzyme, and the hydrolysate is obtained after enzyme inactivation, filtration, concentration and drying; the compound enzyme includes cellulase and protease.

4. The composite composition according to claim 1, characterized in that, The extraction method of the compound herbal extract is water extraction and / or alcohol extraction, and the yield of the extract is 5~15 g of medicinal material / g of extract.

5. The composite composition according to claim 1, characterized in that, The viable count of *Lactobacillus rhamnosus* JYLR-005 is ≥10 billion CFU / g; the viable count of *Bifidobacterium bifidum* B11 is ≥100 billion CFU / g; and the molecular weight of the hydrolyzed collagen peptide is 2000-3000 Da.

6. Use of the composite composition according to any one of claims 1 to 5 in the preparation of health food products that help maintain healthy blood sugar levels.

7. Use of the composite composition according to any one of claims 1 to 5 in the preparation of a medicament for treating type II diabetes.

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