A composition for reducing blood sugar and its application

Abstract

The present invention discloses a composition for reducing blood glucose, the composition comprising a fungal polysaccharide and pyrroloquinoline quinone, wherein the weight ratio of pyrroloquinoline quinone to the fungal polysaccharide is 1.5 to 7.5:1000; it also discloses the use of the composition in the preparation of a hypoglycemic preparation for persistently reducing blood glucose in type 2 diabetes and prediabetes. After continuously taking the composition of the present application for a period of time, even after stopping taking the composition, the blood glucose can remain stable for at least 60 days or more, and has the effect of persistently reducing blood glucose.

Description

Technical Field

[0001] The present invention relates to the technical field of blood glucose reduction, and more specifically, to a composition capable of persistently reducing blood glucose and its applications. Background Art

[0002] Currently, diabetes drugs are mainly used to control blood glucose levels to help prevent complications. According to different mechanisms of action and treatment goals, diabetes drugs can be divided into multiple categories, including insulin: directly supplementing insulin; sulfonylureas: reducing blood glucose by stimulating the pancreas to secrete more insulin; biguanides: reducing the amount of glucose produced by the liver and increasing the body's sensitivity to insulin; thiazolidinediones: increasing the body tissues' sensitivity to insulin and reducing the glucose released by the liver; α-glucosidase inhibitors: slowing down the absorption of carbohydrates in the small intestine, thereby reducing postprandial blood glucose levels; DPP-4 inhibitors: by blocking the action of the DPP-4 enzyme, increasing the level of the incretin hormone GLP-1, thereby promoting insulin secretion and reducing glucagon secretion; GLP-1 receptor agonists and glucagon-like peptide-1 analogs: mimicking the action of the naturally occurring incretin hormone GLP-1 in the human body, increasing insulin secretion and reducing glucagon secretion; SGLT2 inhibitors: preventing the kidneys from reabsorbing glucose, thereby excreting excess glucose through urine.

[0003] Although there are a variety of drugs for controlling blood glucose or treating diabetes, the mechanisms of action of these drugs all act on one or several factors that cause blood glucose to rise. As long as the drug is stopped, these factors will recover and the blood glucose will rise again. Therefore, lifelong medication is required. So far, there is no drug that can completely cure diabetes or keep blood glucose continuously controlled within the normal range after getting off the drug. Summary of the Invention

[0004] In view of the above technical problems in the related art, the present invention provides a composition capable of persistently reducing blood glucose and its applications, which can solve the above problems.

[0005] To achieve the above technical objectives, the technical solution of the present invention is realized as follows:

[0006] A composition for reducing blood glucose, the composition comprising mushroom polysaccharide and pyrroloquinoline quinone, wherein the weight ratio of pyrroloquinoline quinone to mushroom polysaccharide is 1.5 - 7.5:1000.

[0007] Further, the mushroom polysaccharide includes one or more of ganoderma lucidum polysaccharide, pleurotus ostreatus polysaccharide, pleurotus geesteranus polysaccharide, lentinula edodes polysaccharide, agaricus blazei polysaccharide, and grifola frondosa polysaccharide.

[0008] Further, take 4 kg of Pleurotus ostreatus powder, add 5 g of pyrroloquinoline quinone disodium salt, and prepare the powder of the composition after mixing evenly in a small mixer. The content of Pleurotus ostreatus polysaccharide in the Pleurotus ostreatus powder is 30%.

[0009] Further, the application of the composition in the preparation of a hypoglycemic preparation for the persistent reduction of blood glucose in type 2 diabetes and prediabetes.

[0010] The beneficial effects of the present invention: After continuously taking the composition of the present application for a period of time, even after stopping taking the composition, the blood glucose can still be maintained stable for at least 60 days or more, and has the effect of persistently reducing blood glucose. Detailed implementation manners

[0011] The present invention is further described below through examples. It must be pointed out that these examples are for illustrating the present invention and should not be construed as limiting the present invention.

[0012] Explanation about "types of diabetes":

[0013] Diabetes is a chronic metabolic disease, mainly characterized by hyperglycemia (abnormally elevated blood glucose level). Hyperglycemia is usually caused by insufficient insulin secretion or poor response of the body to insulin. Diabetes is mainly divided into two types: type 1 diabetes and type 2 diabetes.

[0014] Type 1 diabetes is caused by the immune system mistakenly attacking and destroying the pancreatic beta cells that produce insulin, resulting in absolute insulin deficiency. Patients with type 1 diabetes need to use insulin therapy for life to maintain life.

[0015] Type 2 diabetes is the most common type of diabetes. This type of diabetes is mainly caused by the decreased efficiency of the body's utilization of insulin (i.e., insulin resistance) and / or insufficient insulin secretion. Type 2 diabetes can be managed through lifestyle changes, oral medications, and in some cases, insulin.

[0016] Explanation about "prediabetes":

[0017] Prediabetes is a transitional stage before the onset of diabetes, a state of intermediate hyperglycemia between normal blood glucose and diabetes, and is the key population for diabetes prevention and control. Generally, fasting blood glucose between 6.1 mmol / L and 6.9 mmol / L or two-hour postprandial blood glucose between 7.8 mmol / L and 11.0 mmol / L or glycated hemoglobin between 5.7% and 6.4% is defined as prediabetes.

[0018] The roles of some raw materials related to the present invention in the treatment of diabetes or blood glucose control:

[0019] (1)Polysaccharides. Currently, there are a large number of animal experiment reports on the alleviating effects of polysaccharides in diabetes and its complications. For example, Astragalus polysaccharide alleviates renal inflammatory response in diabetic nephropathy by inhibiting the TLR4 / NF-κB pathway or promotes autophagy through targeting the lncRNA Gm41268 / PRLR pathway, thus alleviating diabetic nephropathy; Polyporus umbellatus polysaccharide alleviates diabetic symptoms by regulating the intestinal microbiota and the inhibition of the TLR4 / NF-kappaB pathway by the intestinal barrier; Dendrobium officinale polysaccharide reduces podocyte injury in diabetic nephropathy by regulating the IRS-1 / AKT signal and promoting mitosis; Hawthorn polysaccharide alleviates type 2 diabetes symptoms by regulating the intestinal flora and short-chain fatty acids; Zhenzhu Tiaozhi Capsule polysaccharide improves renal injury in diabetic mice by regulating the intestine-kidney axis; Dolichos lablab polysaccharide improves diabetes in type 2 diabetic rats through the intestine-brain axis; Ganoderma lucidum polysaccharide hydrogel accelerates diabetic wound healing by regulating macrophage polarization; Pleurotus ostreatus polysaccharide has an anti-diabetic effect on streptozotocin-induced diabetic rats; Lentinan can help protect pancreatic β-cells, promote insulin secretion, and reduce blood glucose levels; Grifola frondosa polysaccharide or other active substances such as α-glucan in Grifola frondosa alleviate the damage degree of islet β-cells by improving the immune response in the pathogenesis of diabetes, thereby improving diabetes, or improve insulin resistance by regulating the composition of intestinal microbiota in diabetic rats.

[0020] However, these above experimental results are mainly from animal tests, and their effects are concentrated on alleviating the symptoms or complications of diabetes, and have not achieved continuous control of blood glucose within the normal range.

[0021] (2)PQQ (pyrroloquinoline quinone) has been reported to have a hypoglycemic effect, and its mechanism is as follows: Insulin resistance plays a key role in the occurrence and development of type 2 diabetes, and alleviating insulin resistance is considered the main clinical strategy for improving type 2 diabetes. Many evidences show that PTP1B plays a key role in insulin resistance. PTP1B negatively transduces insulin signals by catalyzing the dephosphorylation of tyrosine residues in activated IR and insulin receptor substrate-1. PQQ activates insulin signals independent of ligands by inhibiting cellular PTP1B and enhances glucose uptake in mice through the translocation of glucose transporter 4.

[0022] According to the above mechanism of action, if the administration of PQQ is stopped, the inhibition of insulin signal activation independent of ligands induced by cellular PTP1B will be aborted, and the hypoglycemic effect will be eliminated. Therefore, using PQQ alone cannot achieve the goal of continuously controlling blood glucose within the normal range.

[0023] In summary, whether it is the existing drugs or the raw materials related to the present invention mentioned above, there is a problem of "dependency" for blood sugar reduction, that is: although these drugs and raw materials have the effect of reducing blood sugar, if the use is stopped, the blood sugar will rise back to the original level (so-called "rebound"), and the patient's ability to control blood sugar when separated from the drugs or the above-mentioned raw materials has not been changed.

[0024] In view of the above problems, the present application provides a composition for reducing blood sugar, the composition comprising mushroom polysaccharide, pyrroloquinoline quinone (or pyrroloquinoline quinone salt), wherein the weight ratio of pyrroloquinoline quinone to mushroom polysaccharide is 1.5-7.5:1000. It is applied to type 2 diabetes and prediabetes for persistently reducing blood sugar.

[0025] To demonstrate its effect, the present application is verified through specific case experiments.

[0026] All the raw materials used in the present invention belong to "food" or "substances homologous to medicine and food" in the food catalog, and the daily consumption amount is also strictly controlled within the consumption amount range in the national food catalog. Therefore, there is no safety problem when given to patients.

[0027] In the specific implementation process, the present invention takes 27 patients diagnosed with prediabetes as experimental subjects. The reason for taking patients with prediabetes as experimental subjects is considered from the following three aspects: (1) The blood sugar of patients with prediabetes and diabetic patients is higher than the normal value, only the degree of being higher than the normal value is different, and there is no essential difference in terms of pathology. Therefore, the experimental results obtained with patients with prediabetes as experimental subjects are also applicable to the experimental results with diabetic patients as experimental subjects. (2) According to the current diabetes treatment plan, most diabetic patients need drug control, which will interfere with the use of the composition of the present invention and is not conducive to the test of the effect of the present invention; while patients with prediabetes do not need to use drugs and only need diet control, so it will not interfere with the test results. (3) Considering the safety of the subjects, the blood sugar concentration of diabetic patients is relatively high, and the probability of complications during the test process is also relatively high, and there is a certain risk for the subjects; while patients with prediabetes basically have no risk of complications in the short term (the longest test time does not exceed 3 months).

[0028] Among the 27 patients diagnosed with prediabetes who were subjects in the present invention, there were 11 males and 16 females, aged 35-56 years old, and their fasting blood sugar was 6.1-6.9 mmol / L. All patients followed the doctor's advice and did not use any drugs, and only controlled the blood sugar level through diet. The subjects voluntarily participated, and there was no significant difference in the general information between the experimental group and the control group (P>0.05, see Table 1).

[0029] In the present invention, blood glucose measurement is performed using a home blood glucose meter (brand model: Yuwell 582; manufacturer: Jiangsu Yuwell Medical Equipment Co., Ltd.). The sample is taken as follows: twice a day, respectively within 2 hours after breakfast and dinner, and taken after brewing with 50 - 100 ml of warm water (temperature not exceeding 60 °C).

[0030] Example 1:

[0031] Preparation of the composition of the present invention:

[0032] Take 4 kg of Pleurotus ostreatus powder (Pleurotus ostreatus polysaccharide content is 30%, provided by Hubei Yongxi Biotechnology Co., Ltd.), add 5 g of PQQ (pyrroloquinoline quinone disodium salt, provided by Hubei Meiqi Health Technology Co., Ltd.), mix well in a small mixer, and then pack into bags of 2 g each (for the polysaccharide + PQQ group).

[0033] For the Pleurotus ostreatus powder used in the control experiment, 2 kg of the Pleurotus ostreatus powder raw material is directly packed into bags of 2 g each (for the single polysaccharide group).

[0034] The above samples are all tested according to the GB / T 29602 standard, and can enter the experiment only after meeting the quality standards.

[0035] Example 2:

[0036] Clinical trial:

[0037] The subjects are divided into three groups: a control group, a single polysaccharide group, and a polysaccharide + PQQ group. Among them, the control group follows the doctor's advice and only controls blood glucose levels through diet; the single polysaccharide group, in addition to controlling blood glucose levels through diet, takes Pleurotus ostreatus powder twice a day, one bag each time (i.e., 2 g); the polysaccharide + PQQ group, in addition to controlling blood glucose levels through diet, takes the Pleurotus ostreatus powder + PQQ composition twice a day, one bag each time (i.e., 2 g). All subjects measure their fasting blood glucose before breakfast every day. The subjects in the single polysaccharide group and the polysaccharide + PQQ group stop taking the samples after 30 consecutive days of taking, and continue to measure their fasting blood glucose every day for 60 consecutive days. The test results are shown in Table 1, where: for the single polysaccharide group and the polysaccharide + PQQ group, the fasting blood glucose on the 60th day of the test refers to the data measured 30 days after stopping taking, and the fasting blood glucose on the 90th day of the test refers to the data measured 60 days after stopping taking. The data is shown in the form of "mean ± standard deviation", and the P value is calculated using the T.TEST function built in excel (Microsoft ® Excel for Mac, version: 15.23.2).

[0038] Table 1 Fasting blood glucose values of the subjects

[0039]

[0040] *1, compared with the control group, P > 0.05;

[0041] *2, compared with the control group, P > 0.05; compared with the single polysaccharide group, P > 0.05;

[0042] *3, compared with the control group, P < 0.05;

[0043] *4, compared with the control group, P < 0.05; compared with the single polysaccharide group, P > 0.05;

[0044] *5, compared with the control group, P < 0.05;

[0045] *6, compared with the control group, P < 0.05; compared with the single polysaccharide group, P < 0.05;

[0046] *7, compared with the control group, P > 0.05;

[0047] *8, compared with the control group, P < 0.01; compared with the single polysaccharide group, P < 0.01;

[0048] *9, compared with the control group, P > 0.05;

[0049] *10, compared with the control group, P < 0.05; compared with the single polysaccharide group, P < 0.01.

[0050] The test results of the control group show that for subjects with prediabetes, blood glucose can be stabilized through diet control, but cannot be reduced (P > 0.05 for blood glucose concentration during the test period, no significant difference).

[0051] The test results of the single polysaccharide group show that for subjects with prediabetes, oral administration of a single polysaccharide can effectively reduce fasting blood glucose (compared with the control group after 30 days of administration, i.e., on the 30th day of the test, P < 0.05, with significant difference); however, after stopping the administration, fasting blood glucose will rebound (compared with the control group after 30 days and 60 days of discontinuation, i.e., on the 60th day and 90th day of the test, P > 0.05, no significant difference).

[0052] The test results of the polysaccharide + PQQ group showed that: for pre-diabetic subjects, oral administration of polysaccharide + PQQ could effectively reduce fasting blood glucose (after 30 days of administration, i.e., on the 30th day of the test, compared with the control group, P < 0.01, with a particularly significant difference), and the reduction amplitude was greater than that of oral administration of single polysaccharide (after 30 days of administration, i.e., on the 30th day of the test, compared with the single polysaccharide group, P < 0.05, with a significant difference). And after stopping the administration, this hypoglycemic effect could be maintained for at least more than 60 days (after 30 days of discontinuation, i.e., on the 60th day of the test, compared with the 30th day of the test, P > 0.05, without a significant difference; after 60 days of discontinuation, i.e., on the 90th day of the test, compared with the 30th and 60th days of the test, P > 0.05, without a significant difference).

[0053] The above results indicate that: the combination of polysaccharide + PQQ played a synergistic role in reducing blood glucose, the blood glucose of the subjects was effectively reduced, and the blood glucose was maintained within the normal range within 60 days after stopping taking the sample (there would be no "rebound" phenomenon in a relatively long period, and the problem of "dependency" was solved to a certain extent), achieving the fundamental solution to the problem of high blood glucose.

[0054] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A composition for reducing blood sugar, characterized in that, The composition consists of mushroom polysaccharide and pyrroloquinoline quinone, wherein the weight ratio of pyrroloquinoline quinone to mushroom polysaccharide is 1.5 - 7.5:1000. The composition is a hypoglycemic preparation for persistently reducing blood glucose in the pre-diabetic stage, and the mushroom polysaccharide is Pleurotus ostreatus polysaccharide.

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