Composition for improving diabetes and application thereof

Abstract

The invention provides a composition for improving diabetes mellitus and application of the composition for improving diabetes mellitus. Effective components of the fermented soya bean tea comprise the following components in parts by weight: 30-150 parts of fermented soya bean powder, 30-200 parts of a mulberry leaf extract, 50-500 parts of a white kidney bean extract, 10-100 parts of tea powder, 10-100 parts of sugarcane polyphenol, 35-150 parts of phyllanthus emblica concentrated powder, 50-100 parts of onion powder, 5-25 parts of hydrolyzed collagen, 5-25 parts of momordica grosvenori powder, 50-200 parts of radix puerariae powder, 5-50 parts of ground cinnamon and 50-250 parts of cyclocarya paliurus leaf powder. Most of the components of the composition are medicinal and edible components or food-grade components, so that diabetics can eat the composition for a long time, and the effect of improving and treating diabetes and complications thereof is achieved in a dietary therapy mode.

Description

Technical Field

[0001] The present invention relates to the field of functional foods or health products, and in particular to a composition for improving diabetes and applications thereof. Background Art

[0002] Diabetes is an endocrine and metabolic disease characterized by chronically elevated blood sugar levels. This is caused by weakened pancreatic islet function or insulin resistance, which is caused by a variety of pathogenic factors. With my country's economic development, changes in people's lifestyles and diets, coupled with reduced labor intensity and an aging population, the incidence of diabetes has rapidly increased, making it another major chronic disease that seriously endangers people's health, following cardiovascular and cerebrovascular diseases and cancer.

[0003] Diabetic peripheral neuropathy is a common chronic complication of diabetes, with a statistically significant incidence rate of 30%-90%. With the increasing prevalence of diabetes, symptoms primarily include numbness and pain in the limbs, and can even lead to severe symptoms such as muscle atrophy and difficulty walking, resulting in a significant social and economic burden. The pathogenesis of diabetic peripheral neuropathy is often linked to metabolic disorders, microvascular disease, oxidative stress, autoimmunity, and genetics. Currently, conventional treatments such as dietary control, nerve nutrition, and glucose reduction can slow the progression of diabetic peripheral neuropathy to a certain extent. However, its pathogenesis is often linked to metabolic disorders, microvascular disease, oxidative stress, autoimmunity, and genetics, and conventional treatments still have limitations. Western medicine treatments primarily focus on regulating blood sugar, improving nerve function, combating oxidative stress, improving microcirculation, inhibiting aldose reductase activity, and alleviating pain. While these treatments can alleviate symptoms, they cannot effectively prevent or reverse nerve damage, and long-term medication can lead to drug resistance and adverse reactions. Overall, these treatments are suboptimal, with no significant improvement in long-term quality of life. Traditional Chinese medicine can enhance the body's immunity, improve patients' clinical symptoms and enhance their quality of life through multi-pathway, multi-target and multi-level comprehensive treatment.

[0004] Traditional Chinese medicine has unique advantages in the treatment and prevention of diabetes and shows good development prospects. There are many traditional Chinese medicine compositions for the treatment of diabetes in the prior art, such as: CN102266472B discloses a traditional Chinese medicine composition for preventing and / or treating diabetic nephropathy and a preparation method thereof. The active ingredients of the composition are prepared from the following traditional Chinese medicine raw materials in parts by weight: 1-90 parts of astragalus, 1-60 parts of trichosanthes, 1-12 parts of leech, 1-30 parts of rhubarb, 1-60 parts of anemarrhena, and 1-90 parts of red peony root.

[0005] CN103893620A discloses a traditional Chinese medicine composition for preventing and treating diabetes and a preparation method thereof. The traditional Chinese medicine composition is composed of the following weight ratios: 10-20 parts of verbena, 1-2 parts of unicorn herb, 10-20 parts of coix root, 10-20 parts of coptis root, 10-20 parts of black fungus, 10-20 parts of white fungus, 10-20 parts of glutinous rice, 10-20 parts of coix rice, 10-20 parts of buckwheat, 5-50 parts of honey, and 50-100 parts of vinegar.

[0006] The formulas in the prior art each have their own advantages, but the above compositions are all pharmaceutical ingredients after all and are not suitable for long-term consumption. Summary of the Invention

[0007] In view of the deficiencies of the prior art, the purpose of the present invention is to provide a composition for improving diabetes, most of whose ingredients are medicinal and edible or food-grade ingredients, which can be consumed by diabetic patients for a long time to achieve the effect of improving and treating diabetes through diet therapy.

[0008] In order to achieve the above-mentioned object of the invention, the technical solution of the present invention is: A composition for improving diabetes, wherein the effective ingredients are composed of the following components in parts by weight: 30-150 parts of fermented black bean powder, 30-200 parts of mulberry leaf extract, 50-500 parts of white kidney bean extract, 10-100 parts of tea powder, 10-100 parts of sugarcane polyphenols, 35-150 parts of emblica concentrated powder, 50-100 parts of onion powder, 5-25 parts of hydrolyzed collagen, 5-25 parts of monk fruit powder, 50-200 parts of kudzu root powder, 5-50 parts of cinnamon powder, and 50-250 parts of cyclocarya paliurus leaf powder.

[0009] As a preferred solution in an embodiment of the present invention, its effective ingredients are composed of the following components in parts by weight: 100 parts of fermented black bean powder, 100 parts of mulberry leaf extract, 200 parts of white kidney bean extract, 50 parts of tea powder, 50 parts of sugarcane polyphenols, 100 parts of emblica concentrated powder, 70 parts of onion powder, 15 parts of hydrolyzed collagen, 20 parts of monk fruit powder, 100 parts of kudzu root powder, 30 parts of cinnamon powder, and 120 parts of green willow leaf powder.

[0010] As a preferred solution in an embodiment of the present invention, its effective ingredients are composed of the following components in parts by weight: 50 parts of fermented black bean powder, 50 parts of mulberry leaf extract, 50 parts of white kidney bean extract, 100 parts of tea powder, 20 parts of sugarcane polyphenols, 50 parts of emblica concentrated powder, 50 parts of onion powder, 10 parts of hydrolyzed collagen, 10 parts of monk fruit powder, 50 parts of kudzu root powder, 10 parts of cinnamon powder, and 50 parts of green willow leaf powder.

[0011] As a preferred solution in an embodiment of the present invention, its effective ingredients are composed of the following components in parts by weight: 150 parts of fermented black bean powder, 200 parts of mulberry leaf extract, 400 parts of white kidney bean extract, 100 parts of tea powder, 100 parts of sugarcane polyphenols, 150 parts of emblica concentrated powder, 100 parts of onion powder, 25 parts of hydrolyzed collagen, 25 parts of monk fruit powder, 200 parts of kudzu root powder, 50 parts of cinnamon powder, and 250 parts of green willow leaf powder.

[0012] The raw materials of the composition of the present invention are all existing products that can be purchased in the prior art. The following percentages are all weight percentages, and the present invention preferably selects: Fermented black beans powder: protein content ≥45%; Mulberry leaf extract: 1-DNJ ≥1%; White kidney bean extract: amylase inhibitory activity ≥20000AAIU / g; Tea powder: tea polyphenols content ≥ 20%; Sugarcane polyphenols: in compliance with the new food ingredient announcement; Emblic concentrate powder: β-glucogallin ≥ 10%; Onion powder: Amadori Rearrangement Compounds ≥ 20%; Hydrolyzed collagen: peptide content ≥90%, molecular weight ≤3000 Daltons; Monk fruit powder: mogroside V ≥ 1%; Pueraria root powder: puerarin ≥10%; Cinnamon powder: total polyphenols ≥10%; Cyclocarya paliurus leaf powder: total polysaccharides ≥10%.

[0013] As a preferred solution in the embodiment of the present invention, the powder particle size of the active ingredient is 80 mesh-100 mesh.

[0014] As a preferred solution in an embodiment of the present invention, the preparation method includes the following steps: grinding fermented black bean powder, onion powder, monk fruit powder, kudzu root powder, cinnamon powder, and green willow leaves into fine powder according to the above ratio, and passing through an 80-100 mesh sieve; then mixing evenly with mulberry leaf extract, white kidney bean extract, emblica concentrated powder, tea powder, sugarcane polyphenols, and hydrolyzed collagen, and passing through an 80-100 mesh sieve to obtain a composition.

[0015] The present invention also provides the use of the composition in preparing medicines or health products for treating or improving diabetes.

[0016] Furthermore, the composition can be prepared into tablets, capsules, and powders.

[0017] Furthermore, the diabetes is type II diabetes or complications caused by type II diabetes.

[0018] Furthermore, the diabetes is obese type II diabetes or diabetic foot.

[0019] The following is a further explanation and description of the formulation of the present invention. The following raw materials are all existing products and can be purchased directly.

[0020] Fermented black beans powder: It has the function of inhibiting the activity of α-amylase and α-glucosidase, blocking the digestion and absorption of carbohydrates at the source, intervening in the process of converting starch and sucrose into glucose, and helping to regulate blood sugar.

[0021] Mulberry leaf extract: The active ingredients in mulberry leaves, such as DNJ (1-deoxynojirimycin), can inhibit the activity of α-glucosidase in the small intestine, thereby delaying the decomposition and absorption of carbohydrates and reducing the increase in blood sugar after meals.

[0022] Tea powder: Rich in tea polyphenols, it can improve insulin sensitivity.

[0023] Monk fruit powder: Monk fruit is rich in glycosides, a non-sugar natural sweetener that does not cause significant fluctuations in blood sugar levels, replacing sucrose to reduce glycemic load. Monk fruit is also rich in various antioxidants, which can reduce oxidative stress damage to pancreatic islet cells, protect pancreatic islet function, and thus help maintain normal insulin secretion.

[0024] White kidney bean extract: White kidney bean extract is a natural amylase inhibitor extracted from white kidney beans. Its main active ingredient is α-amylase inhibitory protein.

[0025] Hydrolyzed collagen: repairs cells and protects pancreatic islet function, thus helping to maintain normal insulin secretion function.

[0026] Cinnamon powder: The active ingredient is DL Type A Polymer, which allows insulin (key) to bind to the insulin receptor (keyhole in the lock), smoothly enter the cell to complete metabolism, improve insulin sensitivity, and reduce insulin resistance.

[0027] Sugarcane polyphenols: They inhibit the activity of α-amylase and α-glucosidase. α-amylase breaks down starch and polysaccharides into oligosaccharides, which are then hydrolyzed by α-glucosidase into glucose and other monosaccharides. α-glucosidase hydrolyzes disaccharides, such as sucrose, into glucose and fructose. Sugarcane polyphenols can block active and passive glucose transport, thereby controlling the rate at which glucose enters the bloodstream and reducing the glycemic response after consuming foods containing usable carbohydrates. Sugarcane polyphenols can also help restore the insulin secretion function of damaged pancreatic β-cells.

[0028] Emblic concentrate powder: has the effect of inhibiting amylase and glucosidase; has the effect of inhibiting DPP-4; by inhibiting DPP-4, it reduces GLP-1 degradation and increases insulin secretion.

[0029] Pueraria root powder: Puerarin, flavonoid compounds and other substances in Pueraria root can enhance the insulin sensitivity of patients with newly diagnosed type 2 diabetes by regulating the levels of related sugar and lipid metabolism factors in the patient's body.

[0030] Onion powder: inhibits the activity of α-glucosidase and sucrase.

[0031] Cyclocarya paliurus leaves: rich in polyphenols and flavonoids, which can improve insulin sensitivity.

[0032] Compared with the prior art, the present invention has the following beneficial effects: 1. The fermented black bean powder, mulberry leaf extract, white kidney bean extract, sugarcane polyphenols, emblica fruit concentrated powder, and onion powder in the composition of the present invention inhibit the activities of α-amylase, α-glucosidase, and sucrase, and delay the decomposition and absorption of carbohydrates; the instant tea powder, cinnamon bark, cyclocarya paliurus leaves, and kudzu root powder improve insulin sensitivity; the monk fruit powder and hydrolyzed collagen protect pancreatic islet cells and promote insulin secretion; these ingredients work together to synergistically enhance the effect of lowering and stabilizing blood sugar.

[0033] 2. The composition of the present invention can improve insulin resistance and abnormal lipid metabolism to a certain extent, can reduce the fasting blood glucose level of diabetic rats, and has a good therapeutic effect on obese type II diabetic rats; it can control the excessive release of inflammatory mediators in diabetic foot ulcers, increase the level of growth factors, accelerate wound healing, and has a good therapeutic effect on diabetic foot model rats.

[0034] 3. The composition of the present invention has significant effects and few adverse reactions. Through the synergistic action of multiple mechanisms, the composition not only achieves blood sugar homeostasis regulation, but also significantly improves complications such as diabetic peripheral neuropathy, combining a wide range of therapeutic effects with safety.

[0035] 4. The drug toxicity test of the composition of the present invention on rats after oral administration showed that the composition of the present invention is highly safe and has no toxic side effects.

[0036] 5. Compared with the composition of the comparative party, the composition of the present invention produces a synergistic effect and has better therapeutic effect.

[0037] The detailed structure of the present invention is further described below in conjunction with specific embodiments. DETAILED DESCRIPTION Example 1

[0038] A composition for improving diabetes, comprising the following ingredients and proportions: 100 mg of fermented black bean powder, 100 mg of mulberry leaf extract, 200 mg of white kidney bean extract, 50 mg of instant tea powder, 50 mg of sugarcane polyphenols, 100 mg of emblica concentrated powder, 70 mg of onion powder, 15 mg of hydrolyzed collagen, 20 mg of monk fruit powder, 100 mg of kudzu root powder, 30 mg of cinnamon powder, and 120 mg of cyclocarya paliurus leaf powder.

[0039] The preparation method comprises the following steps: grinding fermented black bean powder, onion powder, monk fruit powder, kudzu root powder, cinnamon powder and cyclocarya paliurus into fine powder according to the above proportions, and passing the powder through an 80-100 mesh sieve; then uniformly mixing the powder with mulberry leaf extract, white kidney bean extract, emblica fruit concentrated powder, instant tea powder, sugarcane polyphenols and hydrolyzed collagen, and passing the powder through an 80-100 mesh sieve to obtain a composition.

[0040] The raw materials are all existing products that can be purchased with the prior art. In this Example 1, the following are selected (the following are all weight percentages): Fermented black beans powder: protein content ≥45%; Mulberry leaf extract: 1-DNJ ≥1%; White kidney bean extract: amylase inhibitory activity ≥20000AAIU / g; Instant tea powder: tea polyphenols content ≥20%; Sugarcane polyphenols: in compliance with the new food ingredient announcement; Emblic concentrate powder: β-glucogallin ≥ 10%; Onion powder: Amadori Rearrangement Compounds ≥ 20%; Hydrolyzed collagen: peptide content ≥90%, molecular weight ≤3000 Daltons; Monk fruit powder: mogroside V ≥ 1%; Pueraria root powder: puerarin ≥10%; Cinnamon powder: total polyphenols ≥10%; Cyclocarya paliurus leaf powder: total polysaccharides ≥10%. Comparative Example 1:

[0041] A composition comprising: 100 mg of fermented black bean powder, 100 mg of mulberry leaf extract, 200 mg of white kidney bean extract, 50 mg of sugarcane polyphenols, and 100 mg of kudzu root powder. The raw materials are derived from the same sources as in Example 1.

[0042] Preparation method: The above raw materials are mixed evenly and then passed through an 80-100 mesh sieve to obtain a composition. The content of the active ingredient in the raw materials is the same as that in Example 1.

[0043] Comparative Example 2: A composition comprising: 100 mg of fermented black bean powder, 100 mg of mulberry leaf extract, 200 mg of white kidney bean extract, 50 mg of instant tea powder, 50 mg of sugarcane polyphenols, 70 mg of onion powder, 20 mg of monk fruit powder, and 100 mg of kudzu root powder. The raw materials are sourced from the same sources as in Example 1. The active ingredient contents of the raw materials are the same as in Example 1.

[0044] The preparation method comprises the following steps: uniformly mixing the above raw materials and then passing the mixture through an 80-100 mesh sieve to obtain the composition.

[0045] Single-dose toxicity study

[0046] Objective: This study was conducted in accordance with the national GLP standard requirements to observe the acute toxic reactions and mortality of SD rats after oral administration of the drug solution of Example 1 twice within 24 hours, and to provide reference data for repeated dose toxicity testing.

[0047] Experimental Methods: Forty SPF-grade Sprague-Dawley rats (half male and half female) weighing 180.1-195.5 g were selected and housed in 475 mm × 350 mm × 200 mm cages, five rats per cage. Animals were housed according to the international (GB14925-2010) environmental requirements for SPF-grade laboratory animals. The animals were quarantined and acclimated for 5 days. They were randomly divided into two groups based on sex and weight: a blank control group (pure water) and a group treated with Example 1 (80 g / kg). Each group consisted of 20 rats, half male and half female. Prior to the experiment, the rats were fasted for at least 12 hours. Purified water and the Example 1 solution were then orally administered at a rate of 15 mL / kg. The drugs were administered twice daily, with a 6-hour interval between doses. Within 0-4 hours after each dose, the rats were carefully observed for signs and characteristics of poisoning, the onset and recovery time of toxic reactions, and any deaths. Observations were conducted once daily in the morning and afternoon for 14 consecutive days. The experimental animals were weighed before administration (on the day of administration) and on the 4th, 7th, 10th and 14th days after administration, and the weight changes and deaths of the experimental animals were recorded.

[0048] Test results: Test results: Effects on general activity, animal poisoning symptoms, and mortality: Within 0 to 4 hours after the end of oral administration, the mice in the blank control group and Example 1 group showed no obvious abnormalities in their spontaneous activity, mental state, and diet, and no related toxic reactions or animal deaths were observed. Continuous observation for 14 days after administration showed no obvious abnormalities in their spontaneous activity, mental state, and diet, and no related toxic reactions or animal deaths were observed.

[0049] Effect on Body Weight: The animals were weighed before dosing (on the day of dosing) and on days 4, 7, 10, and 14 after dosing. No significant differences in body weight were observed between the Example 1 group and the blank control group. This indicates that oral administration of Example 1 to ICR mice had no significant effect on their body weight gain.

[0050] At the end of the experiment, the SD rats were grossly dissected and no obvious abnormalities were found on the surface and cross-section of each organ by naked eye.

[0051]

[0052] 6-month repeated dose toxicity study Objective: This study was carried out in accordance with the national GLP standards to observe the toxic reactions of SD rats after oral administration of different doses of Example 1, to predict the possible clinical adverse reactions caused by Example 1, and to provide a reference for the monitoring and rescue measures of toxic reactions in clinical trials, clinical trials and clinical drug use.

[0053] Methods: 120 SPF SD rats (half male and half female) with a body weight range of 180.0 to 213.8 g and a size of 475 × 350 × 200 mm were selected. 3 Rats were housed in cages, 5 per cage, in accordance with the national standard (GB14925-2010) for SPF-grade laboratory animals. After 5 days of quarantine and acclimatization, the animals were randomly divided into four groups based on body weight: a blank control group, and low-, medium-, and high-dose groups (14.75, 29.50, and 59.00 g / kg) of Example 1, with 30 rats in each group. Each group received 15 mL / kg of the drug by gavage once daily for 6 months (26 weeks), followed by a 4-week drug-free recovery period. At the end of the mid-dose period (week 13), 40 rats were dissected as planned; at the end of the final dosing period (week 26), 40 rats were dissected as planned; and at the end of the recovery period (week 30), 40 rats were dissected as planned. Examinations included general status observation, body weight, food intake, hematological parameters, blood biochemistry, coagulation, organ coefficients, and histopathological examinations.

[0054] result:

[0055] General Condition Observation: Rats were orally administered the Example for 16 months (26 weeks). No significant abnormalities were observed in the animals' physical appearance, mental state, behavioral activity, or secretions and excretions from various cavities. During the trial, all animals were euthanized as planned, and no animals died of abnormal conditions.

[0056] Body weight: Compared with the blank control group during the same period, no abnormalities of toxicological significance were found in the body weights of the various dosage groups in Example 1.

[0057] Food intake: Compared with the blank control group during the same period, the average food intake of each dosage group in Example 1 showed no abnormality of toxicological significance.

[0058] Routine hematological examination: Compared with the blank control group during the same period, no abnormalities of toxicological significance were found in the hematological indicators of each dosage group in Example 1.

[0059] Blood biochemical examination: compared with the blank control group during the same period, no abnormalities of toxicological significance were found in the blood biochemical indicators of each dosage group in Example 1.

[0060] Coagulation test: compared with the blank control group during the same period, no abnormalities of toxicological significance were found in the coagulation indices of each dosage group in Example 1.

[0061] Organ coefficients: Compared with the blank control group during the same period, no abnormalities of toxicological significance were found in the organ coefficients of the various dosage groups in Example 1.

[0062]

[0063] Note: Compared with the blank control group, * P < 0.05.

[0064]

[0065] Note: Compared with the blank control group, * P < 0.05.

[0066]

[0067] Note: Compared with the blank control group, * P < 0.05, ** P < 0.01.

[0068]

[0069] Note: Compared with the blank control group, * P < 0.05, ** P < 0.01.

[0070]

[0071] Note: There was no statistical difference compared with the blank control group.

[0072]

[0073] Note: Compared with the blank control group, * P < 0.05,** P < 0.01.

[0074] Animal pharmacodynamics experimental data

[0075] Experiment 1: Effects of the composition of Example 1 and the comparative example on obese type II diabetic rat model 1. Test purpose: This experiment replicated the obese type II diabetic rat model to investigate the therapeutic effect of the composition of Example 1 on obese type II diabetes, providing a pharmacological basis for the clinical application of the composition of Example 1.

[0076] 2. Test materials: Test substances (test products): the composition of Example 1 (Hunan Yibaiyiyou Biotechnology Co., Ltd.), the composition of Comparative Example 1 (Hunan Yibaiyiyou Biotechnology Co., Ltd.), the composition of Comparative Example 2 (Hunan Yibaiyiyou Biotechnology Co., Ltd.), intended clinical route of administration: oral, 2 g once, 3 times a day, intended clinical course of treatment: 3 months, positive control group, name: metformin, specifications: 0.5 g × 10 tablets × 2 plates, manufacturer: Shanghai Bristol-Myers Squibb Pharmaceuticals Co., Ltd. Experimental animals: 70 SPF-grade SD male rats, weight range: 175-210 g; (Hunan Slake Jingda Experimental Animal Co., Ltd.) 3. Test methods: 3.1 Model preparation and drug administration Seventy SD rats that passed quarantine were selected, and 10 were randomly assigned to a blank control group, receiving a normal diet and free access to water. The remaining rats were fed a high-sugar, high-fat diet for 4 weeks. After 4 weeks of this diet, the rats were fasted for 12 hours and then subjected to an intraperitoneal injection of 35 parts / kg of streptozotocin (STZ) to induce an obese type 2 diabetes model. Five days after STZ injection, the rats were fasted for 12 hours, after which tail vein blood was drawn for fasting blood glucose measurement. A successful model was considered established if the fasting blood glucose value was greater than 11 mmol / L. The rats with successful models were randomly divided into the following groups: a model control group, comparative example 1, comparative example 2, example 1, and a positive control group, with 10 rats in each group. The drug groups were gavaged with the corresponding dose of drug at 5 mL / kg, while the model and blank control groups were gavaged with an equal volume of purified water. Dosing continued for 4 weeks.

[0077] 3.2 Dose setting The proposed clinical dosage of the composition of Example 1 and Comparative Examples 1 and 2 is 6 g / day. The rat clinical equivalent dose, calculated based on body surface area, is: adult dose x 0.018 x 5 = 0.54 g / kg. The metformin (positive control) dose was set at 0.25 g / kg based on literature.

[0078] 3.3 Detection indicators General Observation: During the experiment, closely observe and record the appearance, behavior, secretions, excretions, and diet of each group of animals. If an animal is found dead or dying, perform an autopsy immediately. Weigh the animals weekly.

[0079] Detection indicators After the last dose, the subjects were required to fast for about 12 hours, but not to drink water. Blood was collected using a blood glucose meter to measure the fasting blood glucose level.

[0080] Insulin level detection: The rat serum was collected for insulin level detection.

[0081] 3.4 Result calculation and statistics SPSS 21.0 software was used for statistical analysis. Experimental data are expressed as `x ± S. For comparisons between multiple groups, normality and homogeneity of variance were first compared. When the variances were homogeneous and normal, one-way analysis of variance was used. When normality was not met, the nonparametric T test was used. When normality was met but the variances were not homogeneous, the Tamhane's T2 test was used. If normality was not met, the Kruskal-Wallis test was used, and pairwise comparisons were analyzed using the Mann-Whitney test. P < 0.05 indicated statistical significance, and P < 0.01 indicated that the difference was highly significant.

[0082] 4 Test results 4.1 Effects on fasting blood glucose in rats As shown in Table 8, compared with the blank control group, the fasting blood glucose values of the animals in each group were significantly increased after modeling (P<0.01), and the fasting blood glucose value of the model control group was significantly increased after administration (P<0.01); compared with the model control group, the fasting blood glucose values of Comparative Example 1, Comparative Example 2, Example 1, and the positive control drug were significantly decreased after administration (P<0.05 or P<0.01), and the insulin levels of Example 1 and the positive control group were significantly decreased (P<0.05); the fasting blood glucose value and insulin level of Example 1 were significantly decreased compared with Comparative Example 1 and Comparative Example 2 (P<0.05); the fasting blood glucose value and insulin level of Example 1 were similar to those of the positive control group, and the differences were not statistically significant (P>0.05); the fasting blood glucose value and insulin level of Comparative Example 2 were decreased compared with Comparative Example 1, but the differences were not statistically significant (P>0.05). The results are shown in Table 8. The test results indicate that the composition of Example 1 can significantly reduce the fasting blood glucose value of diabetic rats and has a good improvement effect on insulin resistance.

[0083]

[0084] Note: Compared with the blank control group, "**" indicates P < 0.01, compared with the model control group, indicates P < 0.05, "#" indicates P<0.05 when compared with comparative example 1, and "▲" indicates P<0.05 when compared with comparative example 2. 5. Conclusion: Under the experimental conditions, the compositions of Comparative Examples 1, 2, and Example 1 can reduce fasting blood glucose levels in diabetic rats to varying degrees and have a certain improvement effect on insulin resistance and abnormal lipid metabolism. Example 1 has a better therapeutic effect than Comparative Examples 1 and 2. The synergistic effect of the drugs in Example 1 is more obvious than that in Comparative Examples 1 and 2. The composition of Example 1 has a good therapeutic effect on obese type 2 diabetic rats.

[0085] Experiment 2: Effects of the composition of Example 1 and the comparative example on diabetic foot model rats 1. Purpose of the experiment This experiment replicated the diabetic foot rat model to investigate the therapeutic effect of the composition of Example 1 on diabetic foot, providing a pharmacological basis for the clinical application of the composition of Example 1.

[0086] 2. Test materials: Test substances (test products): the composition of Example 1 (Hunan Yibaiyiyou Biotechnology Co., Ltd.), the composition of Comparative Example 1 (Hunan Yibaiyiyou Biotechnology Co., Ltd.), the composition of Comparative Example 2 (Hunan Yibaiyiyou Biotechnology Co., Ltd.), intended clinical route of administration: oral, 2 g once, 3 times a day, intended clinical course of treatment: 3 months, positive control group, name: metformin, specifications: 0.5 g × 10 tablets × 2 plates, manufacturer: Shanghai Bristol-Myers Squibb Pharmaceuticals Co., Ltd. Experimental animals: 70 SPF-grade SD male rats, weight range: 170-210 g; (Hunan Slake Jingda Experimental Animal Co., Ltd.) 3 Test methods 3.1 Model preparation and drug administration Seventy quarantined SD rats were selected, and 10 were randomly assigned to a blank control group, receiving a normal diet and free access to water. The remaining rats were fed a high-sugar, high-fat diet for 4 weeks. After 4 weeks of this diet, they were fasted for 12 hours and induced with a type 2 diabetes model using streptozotocin (STZ) 35 parts / kg intraperitoneally. Five days after STZ injection, random blood glucose was measured using tail vein blood. A successful model was considered if the fasting blood glucose value was greater than 11 mmol / L. A rectangular mark (3 mm × 7 mm) was stamped on the dorsum of the rat's foot, and the full-thickness skin was excised with scissors, extending deep to the fascia, to create a diabetic foot ulcer wound model. The model rats were randomly assigned to a model control group, comparative example 1, comparative example 2, example 1, and a metformin group (positive control), with 10 rats in each group. The drug groups were gavaged with the corresponding drug dose at 5 mL / kg, while the model and blank control groups were gavaged with an equal volume of purified water. The drugs were administered continuously for 2 weeks. On the 7th and 14th days after administration, the wound surface was covered with filter paper to obtain the area data and calculate the wound healing rate. The day after the last administration, the levels of IL-1, PDGF-BB and other indicators in rat serum samples were detected by ELISA, and the ulcer wound tissues of diabetic foot rats and normal rats were taken for histopathological examination.

[0087] 3.2 Dose setting The proposed clinical dosage of the composition of Example 1 and Comparative Examples 1 and 2 is 6 g / day, which is converted into a rat clinical equivalent dose based on body surface area = adult dose × 0.018 × 5 = 0.54 g / kg. The metformin group dose was set at 0.25 g / kg based on the literature.

[0088] 3.4 Detection indicators General Observation: After modeling and drug administration, closely observe and record the appearance, behavior, secretions, excretions, and diet of each group of animals. If an animal is found dead or dying, perform an autopsy immediately. Weigh the animals weekly.

[0089] Test indicators: Wound healing in rats; on days 7 and 14 after administration, the wounds were covered with filter paper, the area data was obtained, and the wound healing rate was calculated. Wound healing rate = (original wound area - residual wound area) / original wound area × 100%.

[0090] Detection of related factor levels: The day after the last administration, the levels of IL-1, PDGF-BB and other indicators in rat serum samples were detected by ELISA.

[0091] 4 Test results 4.1 Effects on wound healing rate in rats Compared with the blank control group, the healing rates of rats in the model control group were significantly reduced on days 7 and 14 (P < 0.01). Compared with the model control group, the healing rates of rats in Comparative Example 1, Comparative Example 2, Example 1, and the positive control group were significantly increased on days 7 and 14 (P < 0.05 or P < 0.01). The healing rates on days 7 and 14 were significantly increased in Example 1 compared with Comparative Example 1 and Comparative Example 2 (P < 0.05). The healing rates on days 7 and 14 were significantly increased in Comparative Example 2 compared with Comparative Example 1, but the differences were not statistically significant (P > 0.05). The healing rates on days 7 and 14 were significantly increased in Example 1 compared with the positive control group (P < 0.05). The results are shown in Table 9. The experimental results suggest that the composition of Example 1 can promote wound healing in diabetic foot ulcers in rats.

[0092]

[0093] Note: Compared with the blank control group, "**" indicates P < 0.01, compared with the model control group, indicates P < 0.05, "#" indicates P<0.01, compared with comparative example 1, "#" indicates P<0.05, compared with comparative example 2, "▲" indicates P<0.05, compared with the positive control group, "a" indicates P<0.05.

[0094] 4.2 Effects of IL-1 and PDGF-BB Levels in Rat Serum Compared with the blank control group, the serum IL-1 level of rats in the model control group was significantly increased (P<0.01), and the PDGF-BB level was significantly decreased (P<0.01); compared with the model control group, the serum IL-1 level of rats in comparative example 1, comparative example 2, example 1, and the positive control group was significantly decreased (P<0.05 or P<0.01), and the PDGF-BB level was significantly increased (P<0.05 or P<0.01); compared with comparative examples 1 and 2, the serum IL-1 level of rats in Example 1 was significantly decreased (P<0.05), and the PDGF-BB level was significantly increased (P<0.05); compared with comparative example 1, the serum IL-1 level of rats in comparative example 2 was decreased, and the PDGF-BB level was increased, but the differences were not statistically significant (P>0.05); compared with the positive control group, the serum IL-1 level of rats in Example 1 was significantly decreased (P<0.05), and the PDGF-BB level was significantly increased (P<0.05). The results are shown in Table 10. The results indicate that the composition of Example 1 can control the excessive release of inflammatory mediators in diabetic foot ulcers, increase the level of growth factors, and accelerate wound healing.

[0095]

[0096] Note: Compared with the blank control group, "**" indicates P < 0.01, compared with the model control group, "#" indicates P<0.01, compared with comparative example 1, "#" indicates P<0.05, compared with comparative example 2, "▲" indicates P<0.05, compared with the positive control group, "a" indicates P<0.05.

[0097] 5. Conclusion: The experimental results show that under the experimental conditions, the compositions of Comparative Examples 1, 2, and Example 1 can control the excessive release of inflammatory mediators in diabetic foot ulcers, increase growth factor levels, and accelerate wound healing. Example 1 has a superior therapeutic effect compared to Comparative Examples 1 and 2. The composition of Example 1 exhibits a significant synergistic effect compared to the drugs in Comparative Examples 1 and 2. The composition of Example 1 has a favorable therapeutic effect in rats with a diabetic foot ulcer model.

[0098] Clinical analysis data of the composition of Example 1

[0099] General information: According to the standard, 96 patients who met the diagnosis of diabetes were selected for observation and randomly divided into Example 1 and a control group. Among them, in Example 1, there were 26 male patients and 22 female patients, aged 30 to 70 years old, with an average age of (51.27 ± 5.63) years. In terms of the course of diabetes, the course of disease was 3 to 10 years, with an average of (6.35 ± 2.17) years. In terms of the course of peripheral neuropathy, the course of disease was 2 to 8 years, with an average of (4.08 ± 1.25) years. In the control group, there were 25 male patients and 23 female patients, aged 30 to 70 years old, with an average age of (51.87 ± 5.46) years. In terms of the course of diabetes, the course of disease was 3 to 10 years, with an average of (6.12 ± 2.38) years. In terms of the course of peripheral neuropathy, the course of disease was 2 to 8 years, with an average of (4.29 ± 1.36) years. There was no statistically significant difference in the general information between the two groups (P>0.05), indicating that the two groups were comparable.

[0100] Inclusion criteria: (1) All patients met the WHO diagnostic criteria for type 2 diabetes; (2) All patients met the diagnostic criteria for diabetic peripheral neuropathy; (3) All patients were aged ≥30 years; (4) All patients had symptoms such as pain in the extremities and paresthesia; (5) All patients had a positive vibration threshold test.

[0101] Exclusion criteria: breastfeeding and pregnant women, people with a history of drug allergies, people with speech and communication disorders, people with mental illnesses, people with chronic digestive system diseases, people with severe dysfunction of the heart, liver, kidney, etc., people with limb movement dysfunction, people with hematopoietic system diseases, people with acute and chronic infections, people with malignant tumors, and people with mental illnesses.

[0102] Treatment method: The control group took metformin (National Medicine Standard No. H20050699, specification: 0.5g) orally, 0.5g / time, 3 times / day; the Example 1 group took the product of Example 1 of the present invention (provided by Hunan Yibaiyiyou Biotechnology Co., Ltd., 2g / bag) orally, 1 bag each time, 3 times a day. Both groups of patients were treated continuously for 3 months.

[0103] Observation indicators (1) TCM syndrome score. It includes 4 items: pain, numbness, burning, and strange sensation, each with a score of 0 to 3 points, and a total score of 0 to 12 points, ranging from none to severe. (2) Threshold for cold and warm pain sensation. (3) Blood sugar and blood lipid levels. (4) Vibration perception threshold (VPT), including VPT of the dorsum of the foot and the first toe. (5) Observation of the incidence of adverse reactions. (6) Clinical efficacy: Cured: After treatment, the patient has no lower limb discomfort symptoms, the TCM syndrome score and VPT are reduced by 70% to 100%, and life and work return to normal; Significantly effective: After treatment, the patient has basically no or significantly milder symptoms, the TCM syndrome score and VPT are reduced by 50% to 69%, respectively; Effective: After treatment, the patient has milder symptoms, the TCM syndrome score and VPT are reduced by 30% to 49%, respectively; Ineffective: After treatment, the patient's symptoms do not change significantly, the TCM syndrome score and VPT are reduced by 0 to 29%, or do not decrease or even increase. Total effective rate = (cured + markedly effective + effective) ÷ total number of cases × 100% Statistical methods: SPSS 16.0 statistical software was used for data analysis and comparison. The t-test was used for comparison of measurement data, and the chi-square test was used for comparison of enumeration data. P < 0.05 indicated statistical significance.

[0104]

[0105] Note: Compared with the group before treatment, "*" indicates P < 0.05, "**" indicates P < 0.01; compared with the control group after treatment, "#" indicates P < 0.05

[0106] Note: Compared with the group before treatment, "*" indicates P < 0.05, "**" indicates P < 0.01; compared with the control group after treatment, "#" indicates P < 0.05

[0107] Note: Compared with the group before treatment, "*" indicates P < 0.05

[0108] Note: Compared with the group before treatment, "*" indicates P < 0.05, "**" indicates P < 0.01; compared with the control group after treatment, "#" indicates P < 0.05

[0109] Note: Compared with the control group, "*" indicates P < 0.05

[0110] Note: Compared with the control group after treatment, *P<0.05.

[0111] As shown in Tables 11 to 16, the TCM syndrome scores, cool and warm sensation thresholds, blood glucose, and VPT of the two groups of patients before and after treatment were compared: before treatment, there were no statistically significant differences in the pain, numbness, burning, and strange sensation scores and the total TCM syndrome score, cool sensation threshold, warm sensation threshold, pain threshold, fasting blood glucose, 2-hour postprandial blood glucose, dorsum VPT, and first toe VPT of the two groups (P>0.05). After treatment, the pain, numbness, burning, and strange sensation scores and the total TCM syndrome score, cool sensation threshold, warm sensation threshold, fasting blood glucose, 2-hour postprandial blood glucose, dorsum VPT, first toe VPT, and pain threshold of the same group were lower than those before treatment (P<0.05 or P<0.01). After treatment, the fasting blood glucose, 2-hour postprandial blood glucose, dorsum VPT, first toe VPT, and pain threshold of the control group and Example 1 were compared. h blood glucose control group was close to that of Example 1 group, with no statistically significant difference (P>0.05), while other Example 1 groups were lower than the control group (P<0.05); clinical efficacy comparison: Example 1 group had better efficacy than the control group (P<0.05); adverse reaction observation comparison: the incidence of adverse reactions in Example 1 group after treatment was lower than that in the control group, with statistically significant difference ( P <0.05).

[0112] Example 2

[0113] A composition for improving diabetes, the active ingredients of which are: 50 mg of fermented black bean powder, 50 mg of mulberry leaf extract, 50 mg of white kidney bean extract, 100 mg of instant tea powder, 20 mg of sugarcane polyphenols, 50 mg of emblica concentrated powder, 50 mg of onion powder, 10 mg of hydrolyzed collagen, 10 mg of monk fruit powder, 50 mg of kudzu root powder, 10 mg of cinnamon powder, and 50 mg of Cyclocarya paliurus.

[0114] Example 3

[0115] A composition for improving diabetes, comprising the following active ingredients: 150 mg of fermented black bean powder, 200 mg of mulberry leaf extract, 400 mg of white kidney bean extract, 100 mg of instant tea powder, 100 mg of sugarcane polyphenols, 150 mg of emblica concentrated powder, 100 mg of onion powder, 25 mg of hydrolyzed collagen, 25 mg of monk fruit powder, 200 mg of kudzu root powder, 50 mg of cinnamon powder, and 250 mg of Cyclocarya paliurus.

[0116] The formulations, raw material sources, and preparation methods of Examples 2-4 are the same as those of Example 1, with slightly different proportions. Their animal efficacy is similar to that of Example 1, with no significant difference. A detailed description is omitted here.

[0117] The above is a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, who makes equivalent replacements or changes based on the technical solutions and concepts of the present invention, should be covered by the scope of protection of the claims of the present invention.

Claims

1. A composition for improving diabetes, characterized in that: The effective ingredients are composed of the following components in parts by weight: 30-150 parts of fermented black bean powder, 30-200 parts of mulberry leaf extract, 50-500 parts of white kidney bean extract, 10-100 parts of tea powder, 10-100 parts of sugarcane polyphenols, 35-150 parts of emblica concentrated powder, 50-100 parts of onion powder, 5-25 parts of hydrolyzed collagen, 5-25 parts of monk fruit powder, 50-200 parts of kudzu root powder, 5-50 parts of cinnamon powder, and 50-250 parts of cyclocarya paliurus leaf powder.

2. The composition for improving diabetes according to claim 1, characterized in that: The effective ingredients are composed of the following components in parts by weight: 100 parts of fermented black bean powder, 100 parts of mulberry leaf extract, 200 parts of white kidney bean extract, 50 parts of tea powder, 50 parts of sugarcane polyphenols, 100 parts of emblica concentrated powder, 70 parts of onion powder, 15 parts of hydrolyzed collagen, 20 parts of monk fruit powder, 100 parts of kudzu root powder, 30 parts of cinnamon powder, and 120 parts of cyclocarya paliurus leaf powder.

3. The composition for improving diabetes according to claim 1, characterized in that: The active ingredients are composed of the following components in parts by weight: 50 parts of fermented black bean powder, 50 parts of mulberry leaf extract, 50 parts of white kidney bean extract, 100 parts of tea powder, 20 parts of sugarcane polyphenols, 50 parts of emblica concentrated powder, 50 parts of onion powder, 10 parts of hydrolyzed collagen, 10 parts of monk fruit powder, 50 parts of kudzu root powder, 10 parts of cinnamon powder, and 50 parts of cyclocarya paliurus leaf powder.

4. The composition for improving diabetes according to claim 1, characterized in that: The effective ingredients are composed of the following components in parts by weight: 150 parts of fermented black bean powder, 200 parts of mulberry leaf extract, 400 parts of white kidney bean extract, 100 parts of tea powder, 100 parts of sugarcane polyphenols, 150 parts of emblica concentrated powder, 100 parts of onion powder, 25 parts of hydrolyzed collagen, 25 parts of monk fruit powder, 200 parts of kudzu root powder, 50 parts of cinnamon powder, and 250 parts of cyclocarya paliurus leaf powder.

5. The composition for improving diabetes according to any one of claims 1 to 4, characterized in that: The active ingredient is selected from: Fermented black beans powder: protein content ≥45%; Mulberry leaf extract: 1-DNJ ≥1%; White kidney bean extract: amylase inhibitory activity ≥20000AAIU / g; Tea powder: tea polyphenols content ≥ 20%; Sugarcane polyphenols: in compliance with the new food ingredient announcement; Emblica officinalis concentrated powder: β-glucosinolate ≥10%; Onion powder: glucosamine rearrangement compound ≥20%; Hydrolyzed collagen: peptide content ≥90%, molecular weight ≤3000 Daltons; Monk fruit powder: mogroside V ≥ 1%; Pueraria root powder: puerarin ≥10%; Cinnamon powder: total polyphenols ≥10%; Cyclocarya paliurus leaf powder: total polysaccharides ≥10%.

6. The composition for improving diabetes according to any one of claims 1 to 4, characterized in that: The powder particle size of the active ingredient is 80 meshes to 100 meshes.

7. The composition for improving diabetes according to any one of claims 1 to 4, characterized in that: The preparation method comprises the following steps: grinding fermented black bean powder, onion powder, monk fruit powder, kudzu root powder, cinnamon powder, and cyclocarya paliurus leaves into fine powder according to the above ratio, and passing the powder through an 80-100 mesh sieve; then uniformly mixing the powder with mulberry leaf extract, white kidney bean extract, emblica fruit concentrated powder, tea powder, sugarcane polyphenols, and hydrolyzed collagen, and passing the powder through an 80-100 mesh sieve to obtain a composition.

8. Use of the composition according to any one of claims 1 to 4 in the preparation of a composition or preparation for treating or improving diabetes.

9. The use according to claim 8, characterized in that: It is prepared into tablets, capsules and powders.

10. The use according to claim 8, characterized in that: The diabetes is type II diabetes or complications caused by type II diabetes.

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