Metabiotic compositions derived from Lactobacillus helveticus CICC6024, their preparation methods and applications

Abstract

This invention belongs to the field of microbial fermentation and functional food technology, specifically relating to a postbiotic composition derived from *Lactobacillus helveticus* CICC6024, its preparation method, and its applications. The postbiotic composition of this invention achieves multi-target synergistic regulation of blood glucose through three pathways: inhibiting α-amylase and α-glucosidase, significantly improving glucose consumption in insulin-resistant cells, and restoring the activity of key enzymes in glucose metabolism. Using LC-MS / MS peptidomics technology, the components of the postbiotic were systematically analyzed, and 27 fermentation-specific differentially produced peptides were identified, providing a clear material basis for its efficacy and achieving a leap from a "black box" to a "clear map."

Description

Technical Field

[0001] This invention belongs to the field of microbial fermentation and functional food technology, specifically relating to postbiotic compositions derived from Lactobacillus helveticus CICC6024, their preparation methods, and applications. Background Technology

[0002] Blood glucose regulation is crucial for maintaining bodily health. Alpha-amylase and alpha-glucosidase are key enzymes in carbohydrate digestion; inhibiting their activity can delay glucose absorption. Furthermore, improving insulin resistance in peripheral tissues is another core aspect of blood glucose regulation. Therefore, developing blood glucose-lowering products that can simultaneously target multiple sites is of significant value.

[0003] Metabiotics refer to inactivated bacterial cells and their metabolites that are beneficial to the host's health. *Lactobacillus helveticus* is a recognized probiotic, and its fermented milk proteins can produce a variety of bioactive peptides. Chinese invention patent CN120775729A discloses the preparation of a metabiotic with DPP-IV inhibitory activity using specific *Lactobacillus helveticus* fermented goat milk. However, this technology has the following shortcomings: 1) its hypoglycemic mechanism is singular, involving only DPP-IV inhibition (promoting insulin secretion); 2) the material basis of this metabiotic has not been systematically analyzed; 3) the product form is mostly liquid or ordinary milk powder, and its stability, portability, and user compliance need improvement.

[0004] Currently, there are no reports of Lactobacillus helveticus postbiotic products that have had their material basis elucidated through systematic multi-omics technology, and that simultaneously possess highly efficient inhibitory effects on α-amylase / α-glucosidase activity and improve cellular insulin resistance, and can be formulated into rapidly disintegrating tablets. Summary of the Invention

[0005] The technical problem to be solved by the present invention is that the existing Lactobacillus helveticus post-biotics have a single hypoglycemic mechanism, unclear material basis, and limited product form. The present invention provides a Lactobacillus helveticus post-biotic composition with clear multi-target hypoglycemic activity, clear material basis, and can be made into portable immediate-release tablets, as well as the preparation method thereof.

[0006] The technical solution of the present invention is as follows:

[0007] In a first aspect, the present invention provides a metabiotic composition derived from *Lactobacillus helveticus* CICC6024. This composition is prepared by fermenting *Lactobacillus helveticus* CICC6024 in a culture medium containing skim milk powder, followed by centrifugation, collection of the supernatant, inactivation, concentration, and drying. Furthermore, at a concentration of 1.0 mg / mL, the composition exhibits an inhibition rate greater than 90% against both α-amylase and α-glucosidase.

[0008] Preferably, the metabiotic composition contains 27 differentially expressed polypeptides identified by LC-MS / MS peptidomics and specifically generated during fermentation; the amino acid sequences of the 27 differentially expressed polypeptides are shown in SEQ ID NO: 1 to SEQ ID NO: 27.

[0009] Secondly, the present invention provides a method for preparing the post-biotic composition, which ensures the efficient generation of active ingredients by optimizing fermentation conditions, specifically including the following steps:

[0010] S1. Lactobacillus helveticus CICC6024 was inoculated into MRS liquid medium for activation;

[0011] S2. Inoculate the activated strain at an inoculum of 2-3% into a fermentation medium containing 10-14% (preferably 12%) skim milk powder, and ferment at 36-38℃ for 12-14 hours;

[0012] S3. After centrifuging the fermentation broth, collect the supernatant, inactivate the supernatant, concentrate and dry it to obtain the post-genetic composition.

[0013] Thirdly, the present invention provides the use of the said post-biotic composition for the preparation of dual inhibitors of α-amylase and α-glucosidase, and for the preparation of products that improve insulin resistance.

[0014] Fourthly, the present invention provides a blood glucose regulating tablet, the active ingredient of which comprises the post-biotic composition and pharmaceutically or food-grade excipients, the tablet being applicable to the preparation of blood glucose regulating drugs.

[0015] Preferably, the tablet comprises the following components by weight percentage:

[0016] Active ingredient: 10%-50% post-biotic composition;

[0017] Filler: 10-30% microcrystalline cellulose and 20-40% mannitol;

[0018] Adhesive: PVP K30 2-5%;

[0019] Disintegrant: 4-8% PVPP or croscarmellose sodium;

[0020] Lubricant: Magnesium stearate 0.5-1%;

[0021] Acidulant: Citric acid 0.1-0.3%.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. Synergistic effect of multiple targets: The post-biotic composition of the present invention achieves synergistic regulation of blood glucose through three pathways: inhibiting α-amylase and α-glucosidase (inhibition rate of both >90%), significantly improving glucose consumption in insulin-resistant cells, and restoring the activity of key enzymes in glucose metabolism (PEPCK / PK). This results in a more comprehensive hypoglycemic mechanism.

[0024] 2. Clear Material Basis: Through LC-MS / MS peptidomics technology, the composition of postbiotics was systematically analyzed, and 27 fermentation-specific differentially expressed peptides were identified, providing a clear material basis for its efficacy and achieving a leap from "black box" to "clear map".

[0025] 3. Highly innovative product: For the first time, *Lactobacillus helveticus* post-biotic has been successfully formulated into a rapidly disintegrating oral tablet. This dosage form requires no water and disintegrates rapidly in the mouth, making it particularly suitable for the elderly or special populations with swallowing difficulties. It also boasts good stability and portability, overcoming a major bottleneck in the final product development of post-biotics. Attached Figure Description

[0026] Figure 1 The effect of milk powder addition on the in vitro antioxidant activity of biogenics after skim milk fermentation;

[0027] Figure 2 Pie chart showing the percentage of peptides contributing to each protein in the metagenerogenous system;

[0028] Figure 3 The percentage of metabolites identified for SuperClass in each chemical category;

[0029] Figure 4 The percentage of metabolites identified as Class in each chemical category;

[0030] Figure 5 The α-amylase inhibition rate of post-biotics in different fermentation substrates;

[0031] Figure 6 The α-glucosidase inhibition rate of post-biotics in different fermentation substrates;

[0032] Figure 7 The α-glucosidase inhibition rate of unfermented skim milk solution;

[0033] Figure 8 The effect of palmitic acid on the viability of HepG2 cells;

[0034] Figure 9 The effect of post-genetic samples on glucose consumption in HepG2;

[0035] Figure 10 For the determination of phosphoenolpyruvate carboxykinase activity;

[0036] Figure 11 For the determination of pyruvate kinase activity;

[0037] Figure 12 The effect of post-adrenergic content on the flash release time of blood glucose-regulating flash-release tablets;

[0038] Figure 13 The effect of mannitol addition on the flash release time of blood glucose-regulating flash-release tablets;

[0039] Figure 14 The effect of MCC addition on the flash release time of blood glucose-regulating flash-release tablets;

[0040] Figure 15 The effect of PVPP addition on the flash release time of blood glucose-regulating flash-release tablets;

[0041] Figure 16 This is a product image of Lactobacillus helveticus post-biotic glucose-regulating flash-release tablets. Detailed Implementation

[0042] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. However, it should be understood that the specific embodiments of this invention are only for explaining the invention and are not intended to limit the scope of protection of this invention. In the following embodiments, unless specific techniques or conditions are specified, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments used without specified manufacturers are all conventional products that can be obtained commercially.

[0043] Example 1: Optimized preparation of post-biotic compositions

[0044] 1. Strain activation: The freeze-dried Lactobacillus helveticus CICC6024 strain was inoculated into sterile MRS liquid medium, incubated at 37°C for 24 hours, and passaged 2-3 times at a ratio of 1:100 to obtain a highly active bacterial solution.

[0045] 2. Fermentation process optimization:

[0046] Fermentation substrate: Skim milk powder was dissolved in distilled water at a concentration of 12% (w / v), sterilized at 85°C for 20 minutes, and then cooled to 37°C. Casein powder (with an additional 20% lactose) was also used as a control substrate in parallel for systematic comparison.

[0047] Inoculation and fermentation: Inoculate the activated bacterial solution at an inoculation rate of 3% (v / v) and ferment at a constant temperature of 37℃ for 13 hours.

[0048] 3. Extraction and preparation of post-fermentation glycogen: After fermentation, the fermentation broth was centrifuged at 10,000 r / min for 10 minutes at 4℃, and the supernatant was collected. The supernatant was inactivated by heating at 75℃ for 10 seconds to obtain a liquid post-fermentation glycogen extract. The liquid post-fermentation glycogen extract was pre-frozen at -80℃ and then freeze-dried under vacuum (cold trap temperature ≤ -50℃, vacuum degree ≤ 10 Pa, drying for 48 h). The extract was then ground through an 80-mesh sieve to obtain post-fermentation glycogen powder.

[0049] 4. Matrix optimization

[0050] The amount of skim milk powder added was set at 10%, 11%, 12%, 13%, and 14%, with other conditions following the method described above. The DPPH free radical scavenging rate of the post-biotic at a concentration of 1.0 mg / mL was measured, and the results are as follows... Figure 1 As shown, the group with 12% addition exhibits good concentration dependence.

[0051] Example 2: Systemic Material Basis Analysis of Postbiotic Compositions

[0052] 1. Peptidomics analysis (LC-MS / MS) reveals characteristic peptide profiles:

[0053] LC-MS / MS analysis of the post-biotics (skim milk fermentation group and casein fermentation group) obtained in Example 1 identified more than 1500 peptides, mainly derived from milk proteins such as α-S2-casein and β-casein. Figure 2 ).

[0054] Through differential analysis, 27 differentially expressed peptides with high specificity in the skim milk fermentation group were screened out. The set of these peptides (such as SEQ ID NO:1-27, see Table 1) constitutes the unique "molecular fingerprint" of the metabiotic of this invention. In particular, peptides containing "HKEMPFPKYPVEPF" variants can exert hypoglycemic effects by stimulating GLP-1 and inhibiting DPP-IV.

[0055] Table 1. Amino acid sequences of differentially expressed peptides

[0056]

[0057] 2. Untargeted metabolomics analysis (UPLC-HRMS) linking core metabolic pathways:

[0058] (1) UPLC-HRMS analysis was used to screen out 150 significantly different metabolites. Chemical classification statistics ( Figure 3 and Figure 4 Its overall composition was clearly defined. Key differential metabolites include pyruvate, short-chain fatty acids, and amino acid derivatives (Leu-Phe, His-Pro), etc.

[0059] (2) KEGG pathway enrichment analysis showed that these metabolites were significantly enriched in pathways such as pyruvate metabolism, glycine / serine / threonine metabolism, and arginine biosynthesis, which are closely related to sugar metabolism.

[0060] Example 3: Verification of the multi-target, synergistic hypoglycemic activity of the post-biotic composition

[0061] 1. In vitro digestive enzyme inhibition experiment:

[0062] The post-natal vitamin powder prepared in Example 1 and the positive control group acarbose (a commonly used hypoglycemic drug in clinical practice) were formulated into solutions of different concentrations (0.2-1.0 mg / mL) to detect their effects on α-amylase ( Figure 5 ) and α-glucosidase ( Figure 6 The inhibitory activity against α-glucosidase was measured, and a skim milk solution that was not inoculated with Lactobacillus helveticus CICC6024 but underwent the same heat treatment and lyophilization was set up as a negative control. Figure 7 ).

[0063] The results showed that the inhibition of α-amylase and α-glucosidase by the post-fermentation glycogen of skim milk, casein, and acarbose was significantly dose-dependent. At a concentration of 1.0 mg / mL, the inhibition rate of both α-amylase and α-glucosidase by the post-fermentation glycogen of skim milk was greater than 90%. The inhibitory activity of the skim milk group was generally stronger than that of the casein group. This high inhibitory activity is attributed to the fermentation process, as the inhibition rate of the unfermented milk matrix control group was extremely low, which directly demonstrates the source of the post-fermentation activity.

[0064] 2. Cellular level improvement of insulin resistance experiment:

[0065] (1) Model construction: HepG2 cells were treated with 0.063 mM palmitic acid in combination with 100 nM insulin for 24 hours to construct an insulin resistance model (IR-HepG2). The concentration of 0.063 mM palmitic acid was validated ( Figure 8 It effectively induces resistance while having minimal impact on cell viability, resulting in a stable model.

[0066] (2) Experimental groups: Skim milk fermentation post-biotic groups (high, medium, and low doses), casein fermentation post-biotic groups (high, medium, and low doses), a positive control (1 mM metformin), and a blank group (IR-HepG2) were set up. Each group also had a separate control group (normal cells + the same treatment as the corresponding experimental group). The high, medium, and low doses were achieved by diluting the liquid post-biotic extract prepared in Example 1 with water to a mass concentration of 20%, 10%, and 5%, respectively.

[0067] (3) Glucose consumption: In this embodiment, the insulin-resistant HepG2 (IR-HepG2) cell model was used to evaluate the in vitro hypoglycemic activity of different metagenic samples.

[0068] like Figure 9 As shown, the glucose consumption in the blank group was (0.41±0.01) mmol / L, and that in the positive control metformin group was (0.38±0.01) mmol / L. There was no significant difference between the two, indicating that the IR-HepG2 cell model was established stably.

[0069] Compared with the control group, all metagenetic samples increased glucose consumption in IR-HepG2 cells to varying degrees, as detailed below:

[0070] Skim milk group: The glucose consumption at high, medium and low concentrations was (0.99±0.03), (0.69±0.02) and (0.54±0.02) mmol / L, respectively, showing a significant concentration dependence. The high concentration skim milk had the best effect, increasing by about 141% compared with the blank group.

[0071] Casein group: The glucose consumption at high, medium and low concentrations was (0.82±0.03), (0.74±0.02) and (0.74±0.02) mmol / L, respectively. The effects of medium and low concentrations were similar and higher than those of the blank group.

[0072] The above results indicate that post-genetic agent treatment significantly increased glucose consumption in IR-HepG2 cells, suggesting its potential to improve insulin resistance in hepatocytes and promote glucose uptake, with high-concentration skim milk showing the most significant effect.

[0073] (4) Restoring the activity of key enzymes in glucose metabolism: The post-genetic agent can effectively restore the activity of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate kinase (PK) in IR-HepG2 cells.

[0074] In this embodiment, protein normalization was used to eliminate the influence of differences in protein concentration between samples, and the PEPCK activity of the experimental group and the control group under different matrix and concentration conditions was compared and analyzed. Figure 10 The results showed that different treatment conditions had significant effects on enzyme activity: under blank and positive control conditions, the enzyme activity in the control group (1.55 × 10⁻⁶) was significantly lower than that in the control group (1.55 × 10⁻⁶). -4 U / mg protein, 2.25×10 -4 The levels of U / mg protein were all higher than those in the experimental group (1.03 × 10⁻⁶). -4 U / mg protein, 1.77×10 -4U / mg protein); In the skim milk treatment group, enzyme activity showed a significant concentration-dependent bidirectional regulatory characteristic. After treatment with medium-concentration skim milk, the enzyme activity in the control group with prebiotic intervention reached its peak (3.18 × 10⁻⁶ U / mg protein). -4 The concentration of U / mg protein was significantly higher than that of the experimental group (1.69 × 10⁻⁶). -4 The low-concentration skim milk postbiotic group showed that the low-concentration skim milk postbiotic may have a specific activating effect on the enzymes in the experimental group; in the casein treatment group, the enzyme activity was generally at a high level and had good stability, and the enzyme activity of both groups reached the highest value under medium concentration conditions (experimental group 2.71×10). -4 U / mg protein, control group 2.56×10 -4 The small differences between groups (U / mg protein) indicate that the promoting effect of casein postbiotics on enzyme activity was not significantly different and was weakly affected by concentration changes. These results suggest that the regulatory patterns of enzyme activity by skim milk and casein postbiotics are significantly different, and the concentration effect of skim milk postbiotics can serve as a key entry point for further investigation into the enzyme-substrate interaction mechanism.

[0075] Figure 11 The results showed that in the skim milk postbiotic treatment group, the PK activity of the experimental group exhibited a significant concentration-dependent unimodal effect, reaching a peak value (0.3845 × 10⁻⁶) under medium concentration conditions. -3 The concentration of U / mg protein was significantly higher than that of the control group (0.2590×10). -3 The enzyme activity in the control group showed a slow increasing trend with decreasing skim milk concentration (U / mg protein), while the enzyme activity in the control group showed a slow increasing trend with decreasing skim milk concentration, reaching 0.2670×10 at low concentrations. -3 The U / mg protein ratio surpassed that of the experimental group (0.2206×10). -3 U / mg protein); Under high-concentration skim milk conditions, the enzyme activity in the experimental group was 0.3480×10⁻⁶ U / mg protein. -3 The U / mg protein content was still significantly higher than that of the control group (0.2316×10). -3 The concentration of U / mg protein indicates that medium-to-high concentration skim milk has a specific activating effect on PK enzyme in the experimental group.

[0076] The post-biotic of this invention achieves multi-target synergistic regulation of blood glucose by inhibiting carbohydrate digestive enzymes (inhibition rate >90%), promoting glucose consumption in hepatocytes (from 0.41→0.99 mmol / L), and restoring the activity of key enzymes in glucose metabolism (PEPCK / PK).

[0077] Example 4: Development of Orally Rapidly Disintegrating Tablets Based on Metabiotics

[0078] 1. Initial screening and comparison of formulations

[0079] First, various excipient combination schemes were designed to screen the basic properties of tablets, and the results are shown in Table 2.

[0080] Table 2. Effects of different formulation combinations on tablet quality indicators

[0081]

[0082] As shown in Table 2, formulation F2 exhibits the best performance in terms of disintegration time. Compared to F1, F2 appropriately increases the amounts of binder (PVP K30) and disintegrant (PVPP), resulting in a more compact tablet structure and improved hardness. Simultaneously, the appropriate amount of disintegrant still ensures rapid disintegration within a reasonable time. F3 uses starch to partially replace mannitol, and its tablet hardness and disintegration properties are inferior to F2. This is mainly because starch has lower compressibility and adhesive properties than MCC and PVP K30. Therefore, the excipient system of F2 (MCC + mannitol, PVP K30, PVPP) is initially determined as the basis for subsequent optimization studies.

[0083] 2. Single-factor optimization of key excipient dosage

[0084] Based on the F2 excipient system, a single-factor study was conducted on the dosage of the active ingredient (post-biotic powder) and three key excipients (mannitol, MCC, PVPP) to determine the optimal range for each component.

[0085] (1) The effect of the content of post-biotic active powder: such as Figure 12 As shown, with the increase of epigenetic powder content from 10% to 50%, the poor flowability and insufficient compressibility of the active powder itself lead to a decrease in particle flowability, making it prone to sticking and excessive tablet weight difference during tableting, and increasing disintegration time. Considering both drug loading and compressibility, the suitable content range of epigenetic powder is determined to be 10% to 50%.

[0086] (2) Effect of mannitol dosage: such as Figure 13 As shown, with the increase of mannitol dosage from 20% to 50%, the surface smoothness and particle flowability of the tablets significantly improved, and the tablet hardness was moderate. This is because mannitol has good filling properties and can improve the taste. However, when the dosage reaches 50%, due to its solubility characteristics, excessive dosage leads to a denser internal structure of the tablet, and the disintegration time tends to be prolonged. Therefore, the suitable dosage range of mannitol is determined to be 20% to 40%.

[0087] (3) Effect of microcrystalline cellulose (MCC) dosage: such as Figure 14As shown, the tablet formability improved significantly as the MCC dosage increased from 10% to 30%, mainly due to the strong dry binding properties of MCC. However, when the dosage increased to 30%, the tablet disintegration rate began to slow down. This is because a higher proportion of MCC forms a stronger skeletal support, hindering moisture penetration. Therefore, the suitable dosage range for MCC was determined to be 10% to 30%.

[0088] (4) Effect of disintegrant (cross-linked polyvinylpyrrolidone, PVPP) dosage: such as Figure 15 As shown, the disintegration time of tablets significantly decreased with increasing PVPP dosage from 2% to 6%, demonstrating its excellent capillary action and swelling properties. However, when the dosage increased to 8%, the trend of shortening the disintegration time became less pronounced, and excessive PVPP may lead to increased hygroscopicity of the particles. Based on the requirement for rapid disintegration, the suitable dosage range of PVPP was determined to be 4% to 8%.

[0089] 3. Optimal prescription (by weight percentage):

[0090] Lactobacillus helveticus CICC6024 post-biotic powder: 30%;

[0091] Microcrystalline cellulose (MCC): 20%;

[0092] Mannitol: 40%;

[0093] Adhesive PVP K30: 4%;

[0094] Disintegrant (PVPP): 5%;

[0095] Lubricant magnesium stearate: 0.8%;

[0096] Flavoring agent citric acid: 0.2%.

[0097] 4. Process and Product Quality Evaluation

[0098] The above-mentioned formulation tablets were prepared using a wet granulation and tableting process, with a compression pressure of 12 kN. The resulting tablets were uniformly off-white in appearance, with a smooth surface and no visible defects (appearance as shown). Figure 16 The disintegration time test showed that it was 14.4 ± 0.5 seconds, which meets the relevant standards and solves the key technical problems of portability, stability and compliance of Houshengyuan products with elderly patients with swallowing difficulties.

[0099] This invention prepares a post-biotic using a specific strain (CICC6024) and process (12% skim milk powder, 3% inoculum, fermentation at 37°C for 13 hours). For the first time, it combines peptidomics and metabolomics to systematically elucidate the material basis of its rich content of 27 characteristic peptides (such as those containing the HKEMPFPKYPVEPF variant) and related pyruvate metabolism pathways. Furthermore, multi-model experiments fully validated its multi-target, synergistic hypoglycemic activity, ultimately leading to the successful development of a rapidly disintegrating oral tablet with an extremely short disintegration time (14.4 seconds) specifically tailored for a particular population. This invention's technical solution has significant advantages, including clearly defined components and mechanisms, multi-target synergy, ease of use, and precise target population targeting, demonstrating significant progress and inventiveness compared to existing technologies.

Claims

1. A metabiotic composition derived from *Lactobacillus helveticus* CICC6024, characterized in that, It is prepared by fermenting Lactobacillus helveticus CICC6024 in a culture medium containing skim milk powder, followed by centrifugation, collection of supernatant, inactivation, concentration and drying. The composition has an inhibition rate of more than 90% against α-amylase and α-glucosidase at a concentration of 1.0 mg / mL.

2. The metabiotic composition derived from *Lactobacillus helveticus* CICC6024 according to claim 1, characterized in that, The metabiotic composition contains 27 differentially expressed polypeptides, identified by LC-MS / MS peptidomics and specifically generated during fermentation; the amino acid sequences of the 27 differentially expressed polypeptides are shown in SEQ ID NO: 1 to SEQ ID NO:

27.

3. A method for preparing a metabiotic composition derived from *Lactobacillus helveticus* CICC6024, characterized in that, Includes the following steps: S1. Lactobacillus helveticus CICC6024 was inoculated into MRS liquid medium for activation; S2. Inoculate the activated strain into a fermentation medium containing 10-14% skim milk powder at an inoculation rate of 2-3%, and ferment at 36-38℃ for 12-14 hours; S3. After centrifuging the fermentation broth, collect the supernatant, inactivate the supernatant, concentrate and dry it to obtain the post-genetic composition.

4. The use of the post-genetic composition according to claim 1 or 2 in the preparation of a dual inhibitor of α-amylase and α-glucosidase.

5. The use of the post-biotic composition according to claim 1 or 2 in the preparation of food, pharmaceutical or health products for improving insulin resistance.

6. A tablet for regulating blood sugar, characterized in that, Its active ingredients comprise the postbiotic composition as described in claim 1 or 2, and pharmaceutically or food-grade excipients.

7. The tablet according to claim 6, characterized in that, The post-biotic composition comprises 10%-50% by weight in the tablet.

8. The tablet according to claim 7, characterized in that, The excipients include fillers, binders, disintegrants, lubricants, and acidulants.

9. The tablet according to claim 8, characterized in that, The filler comprises 10-30% microcrystalline cellulose and 20-40% mannitol, the binder is 2-5% PVP K30, the disintegrant is 4-8% PVPP or croscarmellose sodium, the lubricant is 0.5-1% magnesium stearate, and the acidulant is 0.1-0.3% citric acid.

10. Use of the tablet according to any one of claims 6-9 in the preparation of a blood glucose regulating drug.

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