A hypoglycemic composition and use thereof

Abstract

The application belongs to the technical field of functional food and health food, and particularly relates to a hypoglycemic composition and application thereof. The hypoglycemic composition comprises the following raw material components in percentage by mass: 22.5%-25% of bacopa saponin I, 15%-20% of momordica charantia glycoside, 10%-15% of polygonatum sibiricum polysaccharide, 0.8%-2.4% of chromium picolinate, 5%-8% of blueberry anthocyanin, and the balance of auxiliary materials. The hypoglycemic composition provided by the application comprises bacopa saponin I, momordica charantia glycoside, polygonatum sibiricum polysaccharide, chromium picolinate and blueberry anthocyanin. The application optimizes the components of the hypoglycemic composition, and the components synergistically improve the body sugar metabolism level and protect the neural cognitive function. The formula is safe and mild, and can be taken for a long time. The formula is used for preventing and improving mild cognitive impairment in a state of diabetes.

Description

Technical Field

[0001] This invention belongs to the field of functional food and health food technology, specifically relating to a hypoglycemic composition and its application. Background Technology

[0002] Diabetes is a prevalent chronic metabolic disease worldwide. Long-term glucose metabolism disorders can cause multi-dimensional and persistent damage to the central nervous system, becoming a significant risk factor for cognitive decline. Diabetes damages brain nerves in two ways: abnormal blood glucose levels directly damage nerve cells, gradually inducing cognitive impairment, and it also continuously disrupts the health of brain microvessels, affecting normal brain function from both structural and functional perspectives.

[0003] Early cognitive decline caused by diabetes manifests as inattention, short-term memory loss, and reduced executive function. As the disease progresses, it can develop into irreversible Alzheimer's disease, placing a heavy burden on patients and society. From the perspective of the damage mechanism, long-term hyperglycemia can impair brain function by inducing neurooxidative stress, inflammatory responses, and the accumulation of advanced glycation end products (AGEs). Hypoglycemia that may occur during diabetes intervention can also rapidly lead to insufficient energy supply to brain cells, potentially causing irreversible brain damage in severe cases.

[0004] Most health products currently on the market have a single function, focusing either solely on blood sugar level regulation or solely on neuroprotection. These single-function products often fail to simultaneously address the root causes of glucose metabolism disorders and the concurrent repair of central nervous system damage, resulting in significantly limited intervention effects. Furthermore, many existing products, in pursuit of rapid efficacy, add highly stimulating active ingredients. Long-term use can easily lead to gastrointestinal discomfort, excessive blood sugar fluctuations, and other additional burdens, and may even induce sudden hypoglycemia, further exacerbating the risk of brain damage. These products completely fail to meet the long-term, gentle daily intervention needs of diabetic patients.

[0005] Therefore, developing a composition based on natural plant active ingredients that is safe, gentle, suitable for long-term use, and has the dual effects of stabilizing blood sugar regulation and protecting brain nerves, to prevent and improve mild cognitive impairment in diabetic patients, would fill a product gap in the current market and have extremely high practical application value. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides a hypoglycemic composition and its application. The hypoglycemic composition provided by this invention includes purslane saponin I, momordicin, polygonatum polysaccharide, chromium picolinate, and blueberry anthocyanins. By optimizing the composition, the components of this invention work synergistically to improve the body's glucose metabolism and protect neurocognitive function. Moreover, this formula is safe and mild, and can be taken long-term to prevent and improve mild cognitive impairment in diabetic patients.

[0007] To achieve the objectives of this invention, the following technical solution is adopted: This invention provides a hypoglycemic composition comprising the following raw material components in weight percentage: purslane saponin I2 2.5%-25%, momordicin 15%-20%, polygonatum polysaccharide 10%-15%, chromium pyridinecarboxylate 0.8%-2.4%, blueberry anthocyanins 5%-8%, with the remainder being excipients.

[0008] During their research, the inventors discovered that when using a compound of Portulaca oleracea saponin extract, momordicin, Polygonatum polysaccharide, chromium picolinate, and blueberry anthocyanins, there is a risk of antagonism between the active ingredients. Portulaca oleracea saponins can damage the molecular structure of Polygonatum polysaccharide, leading to a decrease in its activity.

[0009] The purslane saponin extract mainly contains purslane saponin I, purslane saponin II, and purslane saponin V. The inventors unexpectedly discovered during their research that among the three saponin components, purslane saponin II and purslane saponin V have the greatest destructive effect on the structure of Polygonatum polysaccharides, while purslane saponin I has the least destructive effect. This invention, by using only purslane saponin I, maximizes the preservation of the bioactivity of Polygonatum polysaccharides and achieves effective synergy of the components. The specific reasons are mainly as follows: the multiple hydroxyl groups of pseudopurslane saponin II can significantly increase its hydrogen bond binding sites with Polygonatum polysaccharide molecules, generating stronger competitive forces and interfering with the molecular conformational stability of Polygonatum polysaccharide; pseudopurslane saponin V, due to the lack of a certain stable five-membered heterocyclic structure, may have reduced steric hindrance of its triterpenoid hydrophobic core and more irregular hydrophobic exposed regions, making it easier to embed into the main chain of Polygonatum polysaccharide and disrupt its hydration balance; pseudopurslane saponin I, due to fewer hydroxyl groups on its glycoside side chains and relatively regular overall steric hindrance of its triterpenoid core structure, reduces the chance and intensity of binding with Polygonatum polysaccharide, and is therefore the subtype with the least impact on Polygonatum polysaccharide among the three.

[0010] The hypoglycemic composition provided by this invention combines purslane saponin I, momordicin, polygonatum polysaccharide, chromium picolinate, and blueberry anthocyanins. Compared to existing products that struggle to achieve both stable hypoglycemic effects and neuroprotective effects, this invention specifically adds purslane saponin I. Purslane saponin I exerts a neuroprotective effect, reducing oxidative damage to hippocampal neurons caused by high glucose, helping to improve attention and short-term memory, and delaying neurodegenerative processes. Momordicin, chromium picolinate, and polygonatum polysaccharide synergistically improve insulin sensitivity, steadily controlling blood glucose fluctuations and reducing the continuous damage to nerves from high glucose at its source. Blueberry anthocyanins enhance the antioxidant effect, blocking the deposition of advanced glycation end products (AGEs) in the brain, further reducing the risk of cognitive decline. Simultaneously, polygonatum polysaccharide reduces oxidative stress levels in the brain, decreasing the oxidative damage burden on neurons and assisting purslane saponin I in better protecting the hippocampus and improving memory, resulting in a more significant improvement in neuroprotective effects than when used alone. These two are the core components for synergistic neuroprotective and hypoglycemic effects.

[0011] Preferably, the excipients include fillers, adhesives, and lubricants.

[0012] More preferably, the filler accounts for 26%-42% of the mass of the hypoglycemic composition.

[0013] More preferably, the adhesive is 2%-3% of the mass of the hypoglycemic composition.

[0014] More preferably, the lubricant accounts for 1.6%-2% of the mass of the hypoglycemic composition.

[0015] More preferably, the filler is at least one of lactose, pregelatinized starch, or mannitol.

[0016] More preferably, the adhesive is at least one of povidone K30 or hydroxypropyl cellulose.

[0017] More preferably, the lubricant is at least one of sodium dodecyl sulfate or micronized silica gel.

[0018] The present invention also provides the use of the above-described hypoglycemic composition in the preparation of products for the prevention or improvement of mild cognitive impairment in diabetic states.

[0019] The present invention also provides a formulation comprising the above-described hypoglycemic composition.

[0020] Preferably, the dosage form of the preparation is tablets, pills, granules or capsules.

[0021] The present invention provides a tablet comprising the above-described hypoglycemic composition.

[0022] The present invention also provides a method for preparing the above-mentioned tablets, comprising the following steps: weighing each raw material component according to the formula amount, mixing the pseudopurslane saponin I, bitter melon glycoside, polygonatum polysaccharide, chromium picolinate, blueberry anthocyanin, filler and lubricant evenly, adding binder to granulate, compressing into tablets to obtain tablets.

[0023] Preferably, the time for uniform mixing is 8-15 minutes.

[0024] Preferably, the granulation is fluidized bed spray granulation.

[0025] This invention employs a fluidized bed spray granulation process, which can ensure that the efficacy data deviation between different batches of formulations is less than 5%, exhibits excellent formulation process stability, and has low difficulty in industrialization.

[0026] More preferably, the inlet air temperature of the fluidized bed during granulation is 60-65℃, and the liquid spraying speed is 15-20 rpm.

[0027] Preferably, the granulation process further includes drying and granulation.

[0028] More preferably, the drying temperature is 55-65℃ and the time is 15-30 min.

[0029] More preferably, the particle size of the granulated particles is 16-24 mesh.

[0030] The beneficial effects provided by this invention are: This invention solves the problem of saponin components in purslane saponin extract damaging the molecular structure of Polygonatum polysaccharide by using purslane saponin I. In addition, purslane saponin I and Polygonatum polysaccharide can work synergistically to protect hippocampal nerve tissue and improve memory function on the one hand, and enhance insulin sensitivity on the other hand, thereby improving the overall abnormal state of glucose metabolism and reducing the risk of cognitive impairment caused by glucose metabolism disorder.

[0031] The hypoglycemic composition provided by this invention did not produce any hypoglycemia or intolerance reactions throughout the entire experimental period. The mild properties of the natural plant active ingredients fully meet the requirements for long-term daily use, avoiding the defects of strong stimulating active ingredients on the market that easily cause blood sugar fluctuations and further aggravate brain damage. It has outstanding advantages in long-term medication safety. Detailed Implementation

[0032] The present invention will be further described in detail below through specific embodiments, but this is only for the purpose of helping to understand the present invention and enabling those skilled in the art to implement or use the present invention, and does not constitute any limitation on the present invention.

[0033] The following description is based on specific embodiments.

[0034] Example 1 This embodiment provides a hypoglycemic composition comprising the following raw material components by weight percentage: purslane saponin I 23.5%, momordicin 18%, polygonatum polysaccharide 12%, chromium picolinate 1.6%, blueberry anthocyanin 6%, lactose 33.9%, povidone K30 3%, and sodium lauryl sulfate 2%; This embodiment also provides a tablet, the preparation method of which includes the following steps: Add povidone K30 to water to prepare a 3% (w / v) povidone K30 aqueous solution; Weigh out the following ingredients: Portulaca oleracea saponin I, momordicin, Polygonatum polysaccharide, chromium pyridinecarboxylate, and blueberry anthocyanins. Add lactose and sodium lauryl sulfate to a V-type mixer and mix for 10 minutes. Transfer the mixture to a fluidized bed and set the inlet air temperature to 63°C. Spray the mixture with a povidone K30 aqueous solution at a spray speed of 18 rpm to complete spray granulation. Dry the mixture at 60°C for 20 minutes and granulate it through a 20-mesh sieve. Compress the resulting granules into tablets, each weighing 300 mg.

[0035] Example 2 This embodiment provides a hypoglycemic composition comprising the following raw material components by weight percentage: purslane saponin I 22.5%, momordicin 15%, polygonatum polysaccharide 10%, chromium picolinate 0.8%, blueberry anthocyanins 5%, pregelatinized starch 41.7%, hydroxypropyl cellulose 3%, and sodium lauryl sulfate 2%. This embodiment also provides a tablet, the preparation method of which includes the following steps: Add hydroxypropyl cellulose to water to prepare a 2% (w / v) hydroxypropyl cellulose aqueous solution. Weigh out the following ingredients: Portulaca oleracea saponin I, momordicin, Polygonatum polysaccharide, chromium pyridinecarboxylate, and blueberry anthocyanins. Add them to pregelatinized starch and sodium dodecyl sulfate, and mix for 8 minutes in a V-type mixer. Transfer the mixed material to a fluidized bed, set the inlet air temperature of the fluidized bed to 60°C, and spray hydroxypropyl cellulose aqueous solution at a spray speed of 15 rpm to complete spray granulation. Dry at 55°C for 15 minutes and granulate through a 16-mesh sieve. Compress the obtained granules into tablets, each weighing 300 mg, to obtain the tablets.

[0036] Example 3 This embodiment provides a hypoglycemic composition comprising the following raw material components by weight percentage: purslane saponin I 25%, momordicin 20%, polygonatum polysaccharide 15%, chromium picolinate 2.4%, blueberry anthocyanins 8%, mannitol 26%, povidone K30 2%, and micronized silica gel 1.6%; This embodiment also provides a tablet, the preparation method of which includes the following steps: Add povidone K30 to water to prepare a 5% (w / v) povidone K30 aqueous solution; Weigh out the following ingredients: Portulaca oleracea saponin I, momordicin, Polygonatum polysaccharide, chromium pyridinecarboxylate, and blueberry anthocyanins. Add mannitol and micronized silica gel to a V-type mixer and mix for 15 minutes. Transfer the mixture to a fluidized bed and set the inlet air temperature to 65°C. Spray-granulate the mixture with a povidone K30 aqueous solution at a spray speed of 20 rpm. Dry the mixture at 65°C for 30 minutes and granulate it through a 24-mesh sieve. Compress the resulting granules into tablets, each weighing 300 mg.

[0037] Comparative Example 1 This comparative example provides a hypoglycemic composition and its tablet, which differs from Example 1 in that: The pseudopurslane saponin I used in Example 1 of this invention was replaced with an equal amount of pseudopurslane saponin II; The other components and dosages, preparation methods and process conditions are the same as in Example 1 of this invention.

[0038] Comparative Example 2 This comparative example provides a hypoglycemic composition and its tablet, which differs from Example 1 in that: The pseudopurslane saponin I used in Example 1 of this invention was replaced with an equal amount of pseudopurslane saponin V; The other components and dosages, preparation methods and process conditions are the same as in Example 1 of this invention.

[0039] Comparative Example 3 This comparative example provides a hypoglycemic composition and its tablet, which differs from Example 1 in that: The pseudopurslane saponin I used in Example 1 of this invention was replaced in equal amounts with a mixture of pseudopurslane saponin I, pseudopurslane saponin II and pseudopurslane saponin V, wherein the mass ratio of the three was 1:1:1; The other components and dosages, preparation methods and process conditions are the same as in Example 1 of this invention.

[0040] Experimental Example 1 This validation was conducted using a mouse model of type 2 diabetes mellitus with mild cognitive impairment, constructed using streptozotocin combined with a high-fat diet.

[0041] Male C57BL / 6 mice aged 6-8 weeks and weighing 18-24g were used. Insulin resistance was induced by feeding them a high-sugar, high-fat diet (66.5% basal diet + 10% lard + 20% sucrose + 2.5% cholesterol + 1% sodium cholate) for 4 weeks. Then, they were intraperitoneally injected with 35mg / kg streptozotocin for 5 consecutive days. After 7 days, mice with fasting blood glucose >11.1mmol / L and abnormal cognitive behavior were selected as the type 2 diabetes mellitus combined with mild cognitive impairment mouse model. Seven experimental groups were set up: a blank model control group, Examples 1-3 groups, and Comparative Examples 1-3 groups, with 10 mice in each group. Mice were randomly assigned to groups and administered the medication continuously for 8 weeks. During the 8-week treatment period, Examples 1-3 groups and Comparative Examples 1-3 groups maintained a high-fat diet throughout. The mice were fed a high-fat diet (60% fat content) and administered the drug via gavage once daily at a fixed time. The dosage was 77.5 mg / kg. Before administration, the tablets provided in the examples and comparative examples were ground into a fine powder and prepared into a uniform suspension with 0.5% sodium carboxymethyl cellulose solution. The suspension was prepared and used immediately. The blank model control group was fed a high-fat diet (60% fat content) throughout the entire process and was administered the same volume of 0.5% sodium carboxymethyl cellulose blank solvent as the experimental group via gavage once daily at a fixed time. The rearing environment of the Example 1-3 groups, Comparative Example 1-3 groups, and blank model control group was maintained with a 12-hour light-dark cycle and a constant temperature of 22-24℃. The drinking water and activity conditions of each group were kept consistent throughout the process to avoid phenotypic reversal caused by dietary changes and to ensure the stability of experimental results related to glucose metabolism and cognitive impairment. After administration, the experimental mice were tested as follows: The test items include the rate of decrease in fasting blood glucose, the rate of reduction in positioning and navigation latency, the increase in time spent in the target quadrant, the rate of increase in brain tissue superoxide dismutase activity, and the rate of clearance of advanced glycation end products in brain tissue. The specific test methods are as follows: Fasting blood glucose reduction rate: Blood was collected from the tail of mice after an 8-hour fast, and fasting blood glucose levels were measured using a blood glucose meter. The reduction rate of fasting blood glucose after administration compared to the baseline before administration was calculated using the following formula: Fasting blood glucose reduction rate (%) = (baseline fasting blood glucose value before administration - measured fasting blood glucose value after administration) ÷ baseline fasting blood glucose value before administration × 100%; Morris water maze navigation experiment: Mice were trained in the water maze for 5 consecutive days. The time it took for the mice to find the hidden platform from the entry point was recorded, i.e., the latency period. The reduction rate of the navigation latency period after drug administration compared with the control group was calculated. The calculation formula is as follows: The rate of reduction in the latency period of navigation (%) = (mean latency period of the blank model group - mean latency period of the test substance group) ÷ mean latency period of the blank model group × 100%; Morris water maze spatial exploration experiment: Hidden platforms in the water maze were removed, and the time mice spent in the target quadrant where the original platform was located was recorded within 60 seconds. The improvement in target quadrant time after drug administration compared to the control group was calculated using the following formula: Increase in target quadrant dwell time (%) = (Average target quadrant dwell time in the test substance group - Average target quadrant dwell time in the blank model group) ÷ Average target quadrant dwell time in the blank model group × 100%; Detection of oxidative stress levels in the brain: Brain tissue was collected from sacrificed mice and homogenized. Superoxide dismutase (SOD) activity in the brain tissue was measured using a superoxide dismutase (SOD) assay kit. The increase in SOD activity in the brain tissue after drug administration compared to the control group was calculated using the following formula: The percentage increase in brain tissue superoxide dismutase activity (%) = (mean brain tissue superoxide dismutase activity in the test substance group - mean brain tissue superoxide dismutase activity in the blank model group) ÷ mean brain tissue superoxide dismutase activity in the blank model group × 100%; Assay for the clearance effect of advanced glycation end products (AGEs) in the brain: The content of AGEs in brain tissue homogenate was measured using an enzyme-linked immunosorbent assay (ELISA) kit for advanced glycation end products (AGEs). The clearance rate of AGEs after drug administration compared with the control group was calculated using the following formula: The clearance rate of advanced glycation end products (AGEs) in brain tissue (%) = (mean content of AGEs in brain tissue of the blank model group - mean content of AGEs in brain tissue of the test drug group) ÷ mean content of AGEs in brain tissue of the blank model group × 100%.

[0042] The test results are shown in the table below.

[0043] Table 1 As shown in Table 1, the tablets prepared by combining Portulaca oleracea saponin I, Momordicin, Polygonatum polysaccharide, chromium picolinate, and blueberry anthocyanins in Examples 1-3 of this invention were used to verify the efficacy of the tablets in a mouse model of type 2 diabetes mellitus with mild cognitive impairment constructed by streptozotocin combined with a high-fat diet. The tablets achieved a fasting blood glucose reduction rate of ≥25%, improving glucose metabolism disorders at the source and reducing substrates for advanced glycation end products (AGEs). Simultaneously, they achieved a brain tissue superoxide dismutase activity increase rate of ≥35% and a brain tissue AGE clearance rate of ≥28%, simultaneously clearing brain AGEs. Internal oxidative damage and glycosylation toxic products; it can also achieve a ≥35% reduction in the latency of positioning navigation and an ≥39% increase in the dwell time in the target quadrant, which directly verifies the improvement of spatial working memory and cognitive executive ability. The synergistic intervention of multiple pathways achieves the linkage effect of glucose metabolism regulation and neurocognitive protection. The above results indicate that the hypoglycemic composition provided in this application can synergistically improve glucose metabolism and protect neurocognitive function, reduce the incidence of hypoglycemic events, is safer and milder, and can be taken for a long time to prevent and improve mild cognitive impairment in diabetic states.

[0044] Comparative Examples 1-3 respectively replaced purslane saponin I in the examples with purslane saponin II, purslane saponin V, and a 1:1:1 mixture of these three saponins. The tablets prepared in Comparative Examples 1-3 were used to verify the efficacy in mouse models. All indicators in Comparative Examples 1-3 were lower than those in Examples 1-3, with Comparative Example 1 showing the most significant decrease. The fasting blood glucose reduction rate in Comparative Example 1 was significantly reduced to 12.3%, indicating a significant decrease in its effect on regulating blood glucose homeostasis. The localization latency reduction rate was significantly reduced to 15.8%. The localization latency reduction rate indicates improved spatial learning and memory abilities; this decrease suggests that the drug has a positive effect on cognitive impairment in the model mice. The repair effect of the injury was significantly weakened; the fasting blood glucose reduction rate of Comparative Example 2 was significantly reduced to 14.7%, indicating that its function in regulating glucose metabolism was greatly reduced, and the clearance rate of advanced glycation end products in brain tissue was significantly reduced to 12.2%, indicating that its function in blocking the deposition of glycosylation toxic products in the brain and clearing glycosylation end products was greatly reduced, and it could not effectively alleviate glycosylation neuronal damage in the brain; although Comparative Example 3 contained pseudopurslane saponin I, its fasting blood glucose reduction rate was also reduced to 19.2%, the localization navigation latency shortening rate was reduced to 24.3%, and the clearance rate of advanced glycation end products in brain tissue was reduced to 17.5%, all of which were significantly worse than those of Examples 1-3.

[0045] Therefore, it can be seen that the hypoglycemic composition with pseudopurslane saponin I as the core has a better synergistic effect than pseudopurslane saponin II, pseudopurslane saponin V and the mixture of the three in a 1:1:1 ratio, and can better achieve the dual effect of improving the body's glucose metabolism level and protecting neurocognitive function.

[0046] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A hypoglycemic composition, characterized in that, The raw material components include the following percentages by weight: purslane saponins I2 2.5%-25%, momordicin 15%-20%, polygonatum polysaccharide 10%-15%, chromium pyridinecarboxylate 0.8%-2.4%, blueberry anthocyanins 5%-8%, and the remainder being excipients.

2. The hypoglycemic composition according to claim 1, characterized in that, The auxiliary materials include fillers, adhesives, and lubricants.

3. The hypoglycemic composition according to claim 2, characterized in that, The filler comprises 26%-42% of the mass of the hypoglycemic composition; and / or The adhesive is 2%-3% of the mass of the hypoglycemic composition; and / or The lubricant is 1.6%-2% of the mass of the hypoglycemic composition.

4. The hypoglycemic composition according to claim 2, characterized in that, The filler is at least one of lactose, pregelatinized starch, or mannitol.

5. The hypoglycemic composition according to claim 2, characterized in that, The adhesive is at least one of polyvinylpyrrolidone K30 or hydroxypropyl cellulose.

6. The hypoglycemic composition according to claim 2, characterized in that, The lubricant is at least one of sodium dodecyl sulfate or micronized silica gel.

7. The use of a hypoglycemic composition as described in any one of claims 1-6 in the preparation of a product for preventing or improving mild cognitive impairment in a diabetic state.

8. A formulation, characterized in that, The composition comprises the hypoglycemic composition according to any one of claims 1-6.

9. A tablet, characterized in that, The composition comprises the hypoglycemic composition according to any one of claims 1-6.

10. A method for preparing a tablet as described in claim 9, characterized in that, The process includes the following steps: weighing each raw material component according to the formula amount, mixing the pseudopurslane saponin I, bitter melon glycoside, polygonatum polysaccharide, chromium picolinate, blueberry anthocyanin, filler and lubricant evenly, adding binder to granulate, compressing into tablets to obtain tablets.

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