Traditional Chinese medicine composition for treating diabetes, application of traditional Chinese medicine composition, traditional Chinese medicine preparation and preparation method of traditional Chinese medicine preparation

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, and relates to a traditional Chinese medicine composition for treating diabetes and application thereof, a traditional Chinese medicine preparation and a preparation method. The medicine is prepared from the following raw materials in parts by weight: 10-20 parts of astragalus membranaceus, 10-20 parts of radix polygonati officinalis, 5-15 parts of folium mori, 5-15 parts of gynostemma pentaphylla, 5-15 parts of fried medicated leaven, 3-9 parts of coptis chinensis, 1-5 parts of pseudo-ginseng and 0.5-1.5 parts of cinnamon. The traditional Chinese medicine composition is good in monarch, minister, assistant and guide, and has the effect of improving physical and chemical indexes of diabetics and the like through mutual compatibility. Clinical observation finds that the composition disclosed by the invention can well improve symptoms and signs of patients, is safe in medication, stable and reliable in curative effect and suitable for further popularization and application.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese medicine preparations, and relates to a Chinese medicine composition for treating diabetes and an application thereof, a Chinese medicine preparation and a preparation method thereof. Background Art

[0002] Diabetes mellitus is a disease with a long course, many complications, and serious harm to human health. Its incidence has gradually increased in recent years. Its typical clinical manifestations are polyuria, polydipsia, polyphagia, fatigue, weight loss, or sweet urine, which are basically the same as diabetes in modern medicine. The pathogenesis of diabetes mellitus at the beginning is mainly due to the loss of yin and fluid, and the excess of dryness and heat. Yin deficiency is the root cause, and dryness and heat are the symptoms. The two are mutually causal. The organs affected by diabetes mellitus are mainly the lungs, stomach, and kidneys. Diabetes mellitus will affect the normal operation of qi and blood, causing blood stasis due to poor blood circulation. Nowadays, the treatment of diabetes mellitus, i.e. diabetes, is mainly based on modern medicine. However, this treatment can cause many side effects: it affects the body's metabolism, leading to mental fatigue and decreased appetite; blood sugar fluctuates severely during treatment, especially in elderly patients; the drug has a single pathway of action, and long-term use is prone to drug resistance, and the clinical efficacy is not satisfactory. Traditional Chinese medicine has a good effect on this disease in improving symptoms, preventing and treating complications, etc., and Chinese medicine can be used dialectically to lower blood sugar while regulating the whole body and improving spirits and appetite.

[0003] Diabetes mellitus is also known as diabetes. Among the Western medicines for the treatment of diabetes, metformin hydrochloride is one of the most commonly used drugs, which controls blood sugar levels by reducing the production of glucose in the liver and enhancing insulin sensitivity. In addition, there are some other drugs, such as sulfonylurea drugs, DPP-4 inhibitors, etc., each of which has different mechanisms of action.

[0004] In terms of traditional Chinese medicine, Shenqi Jiangtang Granule is a common preparation, the main ingredients of which include ginseng, astragalus, etc., which has the function of improving immunity and improving metabolism. There are also some traditional Chinese medicine prescriptions disclosed in patents, such as Rehmannia Decoction and Atractylodes Powder. These prescriptions usually combine multiple traditional Chinese medicine ingredients, aiming to nourish yin and qi and strengthen the spleen and stomach to achieve the effect of auxiliary hypoglycemia. Most prescriptions are currently used in clinical practice in the form of decoctions, but traditional Chinese medicine decoctions need to be newly prepared for clinical use, and have the disadvantages of being difficult to preserve, long decoction time, and inconvenient to carry, so they are subject to certain restrictions in clinical application and development. Summary of the invention

[0005] In view of the shortcomings of the prior art, the present invention provides a Chinese medicine composition for treating diabetes. The Chinese medicine composition has been confirmed by precise pharmacological experiments to have excellent therapeutic effects on diabetes, thus solving the problem of uncertain efficacy of the current Chinese medicine composition.

[0006] Specifically, the technical objectives of the present invention are achieved through the following technical solutions:

[0007] The first object of the present invention is to provide a medicine for diabetes, which is composed of the following raw materials in parts by weight: 10-20 parts of astragalus, 10-20 parts of polygonatum, 5-15 parts of mulberry leaves, 5-15 parts of gynostemma pentaphyllum, 5-15 parts of stir-fried Shenqu, 3-9 parts of coptis, 1-5 parts of Panax notoginseng, and 0.5-1.5 parts of cinnamon.

[0008] In a preferred implementation of the present invention, the medicine is composed of the following raw materials in parts by weight: 15 parts of Astragalus, 15 parts of Polygonatum, 10 parts of Mulberry Leaves, 10 parts of Gynostemma Pentaphyllum, 10 parts of Stir-fried Shenqu, 6 parts of Coptis chinensis, 3 parts of Panax notoginseng, and 1 part of Cinnamon.

[0009] The second object of the present invention is to provide a pharmaceutical preparation, which comprises a Chinese medicine composition and a pharmaceutically acceptable excipient, and the preparation is selected from any one of granules, capsules, tablets, decoctions, oral liquids, pills or suppositories;

[0010] In a preferred embodiment of the present invention, the preparation is selected from granules. The third object of the present invention provides a preparation process of granules as follows:

[0011] (1) Take the raw material of claim 1 or 2, add 5 times the volume of ethanol for extraction, and use the filtrate for later use;

[0012] (2) The filtrate of step (1) is dried under reduced pressure at 50-60° C. to obtain a dry paste, and then mannitol and a wetting agent are added, mixed evenly to obtain a soft material, sieved to obtain wet granules, dried, and sized to obtain granules.

[0013] In parts by weight, the ratio of the dry cream to mannitol is 1:1-2, preferably 1:1.5.

[0014] The step (1) is as follows: taking the raw material of claim 1 or 2, adding 5 times the volume of 50-70% ethanol to extract 3 times, each time for 2 hours, combining the filtrate and setting aside;

[0015] The step (2) comprises drying the filtrate of step (1) under reduced pressure at 50-60° C. to obtain a dry paste with a relative density of 1.20-1.25, adding mannitol, and then adding 70% ethanol as a wetting agent, mixing evenly to prepare a soft material, passing through a 14-mesh sieve to prepare wet granules, drying at 60° C. for 1 hour, and sieving through a 20-mesh sieve to prepare the obtained granules.

[0016] In a preferred embodiment of the present invention, the preparation process of the granules is as follows:

[0017] (1) Take 15 parts of Astragalus, 15 parts of Polygonatum, 10 parts of Morus alba, 10 parts of Gynostemma pentaphyllum, 10 parts of Chao Shenqu, 6 parts of Coptis chinensis, 3 parts of Panax notoginseng, and 1 part of Cinnamon bark, add 5 times the volume of 60% ethanol and extract 3 times, each time for 2 hours, combine the filtrate and set aside;

[0018] (2) Drying the filtrate under reduced pressure at 50-60° C. to obtain a dry paste with a relative density of 1.22, adding mannitol, and then adding 70% ethanol as a wetting agent, mixing them evenly to prepare a soft material, passing through a 14-mesh sieve to prepare wet granules, drying at 60° C. for 1 hour, and sieving through a 20-mesh sieve to prepare the resulting granules; wherein the ratio of the dry paste to mannitol is 1:1.5.

[0019] The fourth object of the present invention is to provide the use of the drug in the preparation of a drug for preventing and treating diabetes mellitus, which is diabetes mellitus. The drug can effectively lower blood sugar levels by regulating sugar metabolism in the body and enhancing insulin sensitivity. In addition, the active ingredients contained in the drug also have the effects of improving pancreatic beta cell function and promoting glucose utilization, thereby helping to alleviate diabetes symptoms and improve the quality of life of patients. Through clinical research verification, the drug shows good efficacy and safety in preventing and treating diabetes, providing a new treatment option for diabetic patients.

[0020] In terms of the optimal prescription, Chinese medicine is currently mostly used in the form of decoctions for clinical use. However, Chinese medicine decoctions need to be prepared before use, and have the disadvantages of being difficult to preserve, long decoction time, and inconvenient to carry. Therefore, they are subject to certain restrictions in clinical application and development. Granules are improved on the basis of traditional Chinese medicine decoctions. In combination with modern pharmaceutical technology, the raw medicinal materials are extracted, concentrated, dried, granulated, and packaged to form concentrated Chinese medicine granules. Chinese medicine granules overcome the shortcomings of traditional Chinese medicine decoctions, which are cumbersome, time-consuming, difficult to preserve, and inconvenient to carry. They have the characteristics of accurate dosage, safety and hygiene, easy to carry, easy to store, and ready to take, which are more suitable for today's fast pace of life. With further research on the production management specifications, quality standards, and therapeutic effects of Chinese medicine granules, their advantages have gradually become prominent, and their clinical applications have become more and more extensive. Therefore, in order to make it easier for patients to take the medicine, this study used the extracted dry paste as raw material to prepare granules. The dosage of excipients, wetting agent concentration and drying time were investigated as single factors, the preparation process was optimized, and granules with good appearance and better taste were prepared, laying the foundation for future research.

[0021] The orthogonal design experiment was used to optimize the alcohol extraction process, so the multi-index weighted comprehensive scoring method was used for screening, and GraPhPad Prism 6 was used to process the orthogonal test results. The optimal alcohol extraction process of Xiaoke Fang was preferably extracted 3 times with 50-70% ethanol for 2 hours. The verification test showed that the process was simple, stable and feasible. In order to facilitate patients to take it, after extraction with this process, the alcohol extract was dried under reduced pressure to obtain a dry paste and prepared into granules. The single factor was investigated for the amount of excipients, the concentration of wetting agent, and the drying temperature. The optimal preparation process was screened according to the particle qualification rate, particle properties, and particle dissolution. In a preferred embodiment of the present invention, mannitol was used as a diluent excipient, the ratio of dry paste to excipients was 1:1.0-2.0, the concentration of wetting agent ethanol was 70%, and the soft material was mixed evenly, and the wet granules were made through a 14-mesh sieve, dried at 60°C for 1h, and sieved through a 20-mesh sieve to prepare the obtained granules.

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

[0023] (1) The Chinese medicine composition for treating diabetes of the present invention comprises astragalus, polygonatum odoratum, mulberry leaf, gynostemma pentaphyllum, stir-fried Shenqu, coptis root, notoginseng and cinnamon bark in the above-mentioned proportions, and has all the main, secondary, auxiliary and guiding ingredients, and can improve the physical and chemical indicators of diabetic patients when combined with each other. Clinical observations have shown that the composition of the present invention can well improve the symptoms and signs of patients, significantly superior to the existing Western medicine treatment methods, safe for use, and stable and reliable in efficacy, and suitable for further promotion and application.

[0024] (2) The Chinese medicine composition for treating diabetes of the present invention is prepared into granules. Through single factor experiments, it is found that the key factors such as auxiliary materials, extraction time and number of times are optimized, and the effective ingredients such as calycosin glucoside and ginsenoside obtained are significantly improved. After accelerated tests, the effective substances change less. It can be seen that the preparation process of the present invention is suitable for the preparation of granules of the composition of the present invention, and the inventor has made creative efforts. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 : After 6 weeks of administration, the blood glucose of the model group mice was still significantly higher than normal (P<0.01), indicating that the diabetes model was successfully established, and its hyperglycemia state was relatively stable, which can be used for the screening of drug hypoglycemic pharmacodynamics. Compared with the comparative example groups 1-5, the positive group and the example 1-3 groups had a better hypoglycemic effect (P<0.05 or P<0.01).

[0026] Figure 2 After 6 weeks of administration, the insulin level of the model group mice was significantly higher than that of the normal group (P<0.01), but there was no significant difference between the positive group and the Example 1-3 groups and the Comparative Example groups 1-5 (P>0.05).

[0027] Figure 3 Compared with the normal control group, the serum insulin resistance level of the model group was significantly increased (P<0.01), showing insulin resistance. Compared with comparative examples 1-5, the serum insulin resistance level of Example 1-3 was significantly reduced (P<0.01).

[0028] Figure 4 : Compared with the model group, the TG content in the normal group was significantly different (P<0.01); compared with the positive group and the comparative example 1-5 group, the TG content in the example 1-3 group was significantly reduced (P<0.01).

[0029] Figure 5 : The TC content of the normal group was significantly different from that of the model group (P<0.01); the TC content of the Example 1-3 group was significantly reduced compared with the positive group and the Comparative Example 1-5 group (P<0.01).

[0030] Figure 6 : Compared with the model group, the LDL content in the normal group was significantly different (P<0.01); compared with the positive group and the comparative example 1-5 group, the LDL content in the example 1-3 group was significantly reduced (P<0.01).

[0031] Figure 7 Comparison of FPG, 2hPG and HbA1C before and after treatment in the treatment group showed that 2hPG had a very significant difference (P<0.05), while 2hPG and HbA1C had no significant difference (P>0.05).

[0032] Figure 8 Comparison of FPG, 2hPG and HbA1C in the control group before and after treatment showed that 2hPG had a very significant difference (P<0.05), while 2hPG and HbA1C had no significant difference (P>0.05).

[0033] Fig. 9 There was no significant difference in F-ins between the two groups of patients before treatment (P>0.05); there was no significant difference in F-ins between the two groups of patients after treatment (P>0.05).

[0034] Fig.10 There was no significant difference in HOMA-IR between the two groups of patients before treatment (P>0.05); there was no significant difference in HOMA-IR between the two groups of patients after treatment (P>0.05). Specific embodiments

[0035] The present invention is further explained below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of the present invention. After reading the present invention, various equivalent modifications to the present invention by those skilled in the art all fall within the scope of protection of the claims of this application.

[0036] Example 1: A Chinese medicine composition for treating diabetes and its preparation method

[0037]

[0038]

[0039] The preparation process is as follows:

[0040] (1) Take the prescribed amount of the above Chinese medicinal materials, add 5 times the volume of 50% ethanol, extract three times, each time for 2 hours, and combine the filtrates for later use;

[0041] (2) The filtrate was dried under reduced pressure at 50-60°C to obtain a dry paste with a relative density of 1.20, mannitol (the weight amount was 1 times that of the dry paste) was added, and then an appropriate amount of 70% ethanol was added as a wetting agent. The mixture was mixed evenly to prepare a soft material, which was passed through a 14-mesh sieve to prepare wet granules. The mixture was dried at 60°C for 1 hour, and sieved through a 20-mesh sieve to prepare the resulting granules.

[0042] Example 2: A Chinese medicine composition for treating diabetes and its preparation method

[0043]

[0044] The preparation process is as follows:

[0045] (1) Take the prescribed amount of the above Chinese medicinal materials, add 5 times the volume of 70% ethanol, extract three times, each time for 2 hours, and combine the filtrates for later use;

[0046] (2) The filtrate was dried under reduced pressure at 50-60°C to obtain a dry paste with a relative density of 1.25, mannitol (the weight amount was twice that of the dry paste) was added, and then an appropriate amount of 70% ethanol was added as a wetting agent. The mixture was mixed evenly to prepare a soft material, which was passed through a 14-mesh sieve to prepare wet granules. The mixture was dried at 60°C for 1 h, and sieved through a 20-mesh sieve to prepare the resulting granules.

[0047] Example 3: A Chinese medicine composition for treating diabetes and its preparation method

[0048]

[0049]

[0050] The preparation process is as follows:

[0051] (1) Take the prescribed amount of the above Chinese medicinal materials, add 5 times the volume of 60% ethanol, extract three times, each time for 2 hours, and combine the filtrates for later use;

[0052] (2) The filtrate was dried under reduced pressure at 50-60°C to obtain a dry paste with a relative density of 1.22, mannitol (the weight dosage is 1.5 times that of the dry paste) was added, and then an appropriate amount of 70% ethanol was added as a wetting agent. The mixture was mixed evenly to prepare a soft material, which was passed through a 14-mesh sieve to prepare wet granules. The mixture was dried at 60°C for 1 h, and sieved through a 20-mesh sieve to prepare the resulting granules.

[0053] Comparative Example 1: A Chinese medicine composition for treating diabetes and its preparation method

[0054]

[0055] The preparation process is the same as that of Example 3.

[0056] Comparative Example 2: A Chinese medicine composition for treating diabetes and its preparation method

[0057]

[0058]

[0059] The preparation process is the same as that of Example 3.

[0060] Comparative Example 3: A Chinese medicine composition for treating diabetes and its preparation method

[0061]

[0062] The preparation process is the same as that of Example 3.

[0063] Comparative Example 4: A Chinese medicine composition for treating diabetes and its preparation method

[0064]

[0065] The preparation process is the same as that of Example 3.

[0066] Comparative Example 5: A Chinese medicine composition for treating diabetes and its preparation method

[0067]

[0068]

[0069] The preparation process is the same as that of Example 3.

[0070] 1. Pharmacological Experiments of the Chinese Medicine Composition of the Present Invention

[0071] 1.1 Experimental Animals:

[0072] 70 db / db mice (spontaneous type 2 diabetic mice caused by defective leptin receptor gene on chromosome 4), SPF grade, male, weighing 33.5±2.7g, and 10 db / m male mice of the same age, weighing 20.5±2.5g, were purchased from Jiangsu Cuiyaokang Biotechnology Co., Ltd.

[0073] 1.2 Dosage and grouping

[0074] 1.2.1 Dosage and route of administration

[0075] The granules prepared in Examples 1-3 and Comparative Examples 1-5 were administered to mice by gavage at a dose of 9.1 mg / kg, calculated based on the raw drug amount, once a day, at 8:00-9:00 a.m., for 6 consecutive weeks, based on the human body weight of 70 kg.

[0076] Positive group: Metformin hydrochloride capsules, national medicine standard number H19991009, specification 0.25g.

[0077] Model group: The same mass of 0.9% saline was given by gavage.

[0078] Normal group: The same mass of 0.9% saline was given by gavage.

[0079] 1.2.2 Grouping

[0080] According to the principle of random grouping, 100 db / db mice with fasting blood glucose greater than 11.1 mmoL / L were selected and divided into 10 cages with 10 mice in each cage. The mice were randomly assigned to the model group, positive group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, and Comparative Example 5 group according to blood glucose and body weight, and 10 mice in the normal group were taken as controls.

[0081] 1.3 Detection Method

[0082] 1.3.1 Blood glucose monitoring

[0083] All mice were fasted for 8 hours at the same time every week, and blood was collected from the orbital vein to measure fasting blood glucose, insulin, and insulin sensitivity index. Insulin sensitivity index = fasting insulin (uU / mL) x fasting blood glucose (mmol / L) / 22.5.

[0084] 1.3.2 Biochemical index detection

[0085] At the end of the 6th week after administration, the mice were fasted but not watered for 12 h. One hour after intragastric administration, blood was collected from the eyeballs and centrifuged at 12000 r / min and 4°C for 8 min. The supernatant was collected and the plasma was collected after centrifugation and stored at -20°C for later use. TC, TG and LDL in the serum were measured using a multifunctional microplate reader.

[0086] 1.4 Statistical analysis

[0087] All experimental data were analyzed using GraPhPad Prism 8 software, and the results were expressed as X±s. One-way analysis of variance was used for comparison among multiple groups, and non-parametric tests were used when the data did not conform to normal distribution. P < 0.05 was considered statistically significant. Statistical graphs were drawn using GraPhPad Prism 8 software.

[0088] 1.5 Results Analysis

[0089] Figure 1 : After 6 weeks of administration, the blood glucose of the model group mice was still significantly higher than normal (P<0.01), indicating that the diabetes model was successfully established, and its hyperglycemia state was relatively stable, which can be used for the screening of drug hypoglycemic pharmacodynamics. The positive group and the Example 1-3 group had a better hypoglycemic effect than the comparative example group 1-5 (P<0.05 or P<0.01). Example 1-3 has a significant hypoglycemic effect and is suitable for further promotion.

[0090] Figure 2 After 6 weeks of administration, the insulin level of the model group mice was significantly higher than that of the normal group (P<0.01), but there was no significant difference between the positive group and the Example 1-3 groups and the Comparative Example groups 1-5 (P>0.05).

[0091] Figure 3 Compared with the normal control group, the serum insulin level in the model group was significantly increased (P<0.01), showing insulin resistance. After drug administration, the insulin sensitivity index value of the control group 1-5 was greater than 2.69, which was determined to be insulin resistance.

[0092] Figure 4 : The data showed that the TG content in the normal group was significantly different from that in the model group (P<0.01); the TG content in the Example 1-3 group was significantly reduced compared with the positive group and the Comparative Example 1-5 group (P<0.01), indicating that the granule prescription of the present invention has the effect of significantly reducing the TG content and is suitable for further promotion and application.

[0093] Figure 5 : The data showed that the TC content of the normal group was significantly different from that of the model group (P<0.01); the TC content of the Example 1-3 group was significantly reduced compared with the positive group and the Comparative Example 1-5 group (P<0.01), indicating that the granule prescription of the present invention has the effect of significantly reducing the TC content.

[0094] Figure 6 : The data showed that the LDL content in the normal group was significantly different from that in the model group (P<0.01); the LDL content in the Example 1-3 group was significantly reduced compared with the positive group and the Comparative Example 1-5 group (P<0.01), indicating that the granule prescription of the present invention has the effect of significantly reducing the LDL content.

[0095] 2. Clinical Trials of the Chinese Medicine Composition of the Present Invention

[0096] 2.1 Judgment criteria

[0097] 2.1.1 Western medicine judgment standards

[0098] The diagnostic criteria for diabetes in the "Guidelines for the Prevention and Treatment of Type 2 Diabetes in China" (2020) of the Diabetes Branch of the Chinese Medical Association were adopted.

[0099] (1) Symptoms of diabetes and random blood glucose (VPG) ≥ 11.1 mmol / l. Random refers to any time after a meal;

[0100] (2) Fasting blood glucose (FPG) ≥ 7.0 mmol / l. The fasting state requires abstention from caloric intake for at least 8 hours;

[0101] (3) 2-hour blood glucose (2hPG) ≥11.1mmol / l after oral glucose tolerance test (OGTT).

[0102] 2.1.2 Chinese medicine judgment standards

[0103] With reference to the "Terms of Clinical Diagnosis and Treatment of Traditional Chinese Medicine·Syndrome Section", the syndrome differentiation standard of damp-heat syndrome with blood stasis was formulated.

[0104] (1) Main symptoms: thirst without desire to drink water, heaviness and fatigue, and loss of appetite;

[0105] (2) Secondary symptoms: numbness and tingling in the limbs, sticky stools, and scanty urination;

[0106] Tongue and pulse: The tongue is dark or has petechiae and ecchymosis, the tongue coating is thick, greasy and slightly yellow, and the pulse is moist, fine and rapid.

[0107] 2.2 Treatment options

[0108] A total of 96 cases were randomly divided into a control group and a treatment group.

[0109] Control group: taking metformin sustained-release tablets, specification: 0.5g / tablet, dosage: 1 tablet each time, twice a day.

[0110] Treatment group: taking the granules of Example 3, Usage and dosage: oral, 2 times a day, half an hour after a meal with boiled water, once in the morning and once in the evening. Treatment course: 2 months.

[0111] 2.3 Efficacy evaluation criteria

[0112] 2.3.1 Criteria for determining the efficacy of Western medicine

[0113] Refer to the efficacy evaluation criteria in the 2007 "Guidelines for the Prevention and Treatment of Diabetes with Traditional Chinese Medicine".

[0114] Marked effect: fasting blood sugar and blood sugar 2 hours after meal dropped to normal range; fasting blood sugar and blood sugar 2 hours after meal dropped by more than 40% of pre-treatment level; glycosylated hemoglobin dropped to normal level, or dropped by more than 30% of pre-treatment level.

[0115] Effective: Fasting blood sugar and 2-hour postprandial blood sugar decreased by more than 20% before treatment, but did not reach the marked effect standard; glycosylated hemoglobin value decreased by more than 10% before treatment, but did not reach the marked effect standard.

[0116] Ineffective: fasting blood sugar and 2-hour postprandial blood sugar did not decrease, or the decrease did not reach the effective standard; glycosylated hemoglobin value did not decrease, or the decrease did not reach the effective standard.

[0117] 2.3.2 Criteria for determining efficacy of TCM syndromes

[0118] Refer to the "Guidelines for Clinical Research of New Chinese Medicines for the Treatment of Diabetes" issued by the Ministry of Health of the People's Republic of China in 2003

[0119] Markedly effective: clinical symptoms and signs of TCM are significantly improved, and the symptom score is reduced by ≥70%;

[0120] Effective: Clinical symptoms and signs of TCM have improved, and the symptom score has decreased by ≥30%; but it has not reached the standard of marked effect;

[0121] Ineffective: No significant improvement in TCM clinical symptoms and signs, or a decrease in symptom scores of ≤30%;

[0122] Note: The calculation formula (nimodipine method) is: [(score before treatment - score after treatment) ÷ score before treatment] × 100%.

[0123] According to the above efficacy evaluation criteria,

[0124] Marked effect: if the TCM syndrome efficacy judgment criteria and the Western medicine efficacy judgment criteria are met, it is markedly effective;

[0125] Effective: If any one of the TCM syndrome efficacy judgment criteria and the Western medicine efficacy judgment criteria is met, it is effective;

[0126] Ineffective: If both the TCM syndrome efficacy judgment criteria and the Western medicine efficacy judgment criteria are met, it is effective.

[0127] 2.3.3 Detection of FPG, 2hPG, and HbA1C

[0128] The judgment will be made with reference to the "TCM Diagnosis and Treatment Plans for 22 Specialties and 95 Diseases" published by the State Administration of Traditional Chinese Medicine.

[0129] FPG (fasting blood glucose) and 2hPG (2-hour postprandial blood glucose) are important indicators for early screening of diabetes. FPG refers to the blood glucose test value 8-10 hours after fasting, while 2hPG refers to the blood glucose value about 1 to 2 hours after a meal. The changes in these two indicators can directly reflect the patient's blood glucose control and are of great significance for determining whether the patient is at risk of complications1.

[0130] HbA1c (glycosylated hemoglobin) is the "gold standard" for testing diabetic patients. The change in its concentration is directly correlated with the average blood sugar concentration of the patient during that period. HbA1c is not easily affected by blood sugar fluctuations, so it can more objectively reflect the average blood sugar level of diabetic patients within 2 to 3 months. This indicator is not only used for clinical diagnosis, but also can intuitively reflect the long-term blood sugar control of diabetic patients.

[0131] 2.3.4 Detection of F-ins and HOMA-IR

[0132] The reference value of F-ins is usually 4.0-23.4Pmol / L, which is the fasting blood sugar value. HOMA-IR refers to the insulin resistance index. The insulin resistance index is mainly used as an indicator to evaluate insulin resistance. Its calculation method is to detect the patient's fasting insulin and fasting venous blood sugar.

[0133] 3. Results

[0134] Figure 7 Comparison of FPG, 2hPG and HbA1C before and after treatment in the treatment group showed that 2hPG had a very significant difference (P<0.05), while 2hPG and HbA1C had no significant difference.

[0135] Figure 8 Comparison of FPG, 2hPG and HbA1C before and after treatment in the control group showed that 2hPG had a very significant difference (P<0.05), while 2hPG and HbA1C had no significant difference.

[0136] Fig. 9 There was no significant difference in F-ins between the two groups of patients before treatment (P>0.05); there was no significant difference in F-ins between the two groups of patients after treatment.

[0137] Fig.10 There was no significant difference in HOMA-IR between the two groups of patients before treatment (P>0.05); there was no significant difference in HOMA-IR between the two groups of patients after treatment (P>0.05).

[0138] Table 1 Comparison of treatment effects between the two groups of patients

[0139]

[0140]

[0141] 3. Single factor experiment to screen the best granule process

[0142] The following experiment is a variation of the single factor experiment based on Example 3. Examples 1-3 are the selected technical routes. By systematically analyzing the influence of various factors, the granule process finds the best preparation conditions, thereby improving the overall performance of the drug preparation. The specific operation is as follows:

[0143] 3.1 [Determination of calycosin glucoside] According to the high performance liquid chromatography method (General Rule 0512)

[0144] Chromatographic conditions and system suitability test, using octadecylsilane bonded silica gel as filler; acetonitrile as mobile phase A, 0.2% formic acid solution as mobile phase B for gradient elution as specified in the following table; detection wavelength is 260nm.

[0145]

[0146] Preparation of reference solution: Take an appropriate amount of calycosin glucoside reference substance, weigh accurately, and add methanol to make a solution containing 50ug per 1ml.

[0147] Preparation of test solution: Take about 1g of the powder of this product (passed through a No. 4 sieve), weigh accurately, place in a round-bottom flask, accurately add 50ml of methanol, weigh, heat and reflux for 4 hours, cool, weigh again, make up the lost weight with methanol, shake well, filter, accurately measure 25ml of the filtrate, recover the solvent to dryness, dissolve the residue in methanol, transfer to a 5m volumetric flask, add methanol to the scale, shake well, and obtain. Determination method: Accurately aspirate 10ml of the reference solution and the test solution respectively, inject into the liquid chromatograph, and determine.

[0148] 3.2 [Content determination] Determine according to the high performance liquid chromatography method (General Rule 0512).

[0149] Chromatographic conditions and system suitability test, using octadecylsilane bonded silica gel as filler; acetonitrile as mobile phase A, water as mobile phase B, gradient elution as specified in the following table; detection wavelength is 203nm.

[0150]

[0151] Preparation of reference solution: Accurately weigh ginsenoside Rgi reference substance, ginsenoside Re reference substance and ginsenoside Rb reference substance, add methanol to make a mixed solution containing 0.2 mg of each substance per 1 ml, shake well, and obtain.

[0152] Preparation of test solution: Take about 1g of the powder of the product (passed through No. 4 sieve), accurately weigh it, place it in a Soxhlet extractor, add chloroform and heat to reflux for 3 hours, discard the chloroform solution, evaporate the solvent from the residue, move it into a 100ml conical flask together with the filter paper tube, accurately add 50ml of water-saturated n-butanol, plug it, leave it overnight, ultrasonically treat it (power 250W, frequency 50kHz) for 30 minutes, filter, discard the initial filtrate, accurately measure 25ml of the subsequent filtrate, place it in an evaporating dish and evaporate it to dryness, dissolve the residue in methanol and transfer it to a 5ml volumetric flask, add methanol to dilute to the scale, shake well, filter, and take the subsequent filtrate.

[0153] Determination method: Accurately pipette 10ml of reference solution and 10-20ml of test solution respectively, inject into liquid chromatograph, and determine.

[0154] 3.3 Accelerated test conditions

[0155] Place in a constant temperature and humidity chamber at high temperature (40°C) and high humidity (relative humidity 75±5%) for an accelerated 6-month test. Preparation of granules containing the Chinese medicine composition of the present invention

[0156] 3.4 Investigation of extraction times and time

[0157] Table 2 Effects of extraction times and time on isoflavone glucosides, etc.

[0158]

[0159] It can be seen from Table 2 above that when the number of extractions is 3 times and the extraction time is 2 h, the contents of calycosin glucoside, ginsenoside Rg1, the total amount of Re and ginsenoside Rb1 are higher and the most economical.

[0160] 3.5 Alcohol Extract and Concentration Selection

[0161] Table 3 Effect of alcohol types on effective substances

[0162]

[0163] Table 4 Effect of ethanol concentration on effective substances

[0164]

[0165] As can be seen from Table 3 and Table 4, ethanol is the best as the extracting solution. At the same time, the concentration is selected. It is found that when the ethanol concentration is 50-70%, the content of the active substance is the highest. Therefore, the alcohol used in the present invention is ethanol, and the concentration is 50-70%.

[0166] 3.6 Selection of excipients for granules

[0167] Excipients in traditional Chinese medicine are the most critical to the formation of preparations. Several commonly used excipients were selected, such as starch, polyvinyl pyrrolidone, microcrystalline cellulose, etc. This experiment investigated the effects of excipients on the content of calycosin glucoside, ginsenoside Rg1, Re total amount and ginsenoside Rb1 under accelerated experimental conditions.

[0168] Table 5 Effect of different excipients on the content of calycosin isoflavone glucose (mg / g)

[0169]

[0170]

[0171] Table 6 Effect of different excipients on the total amount of ginsenoside Rg1 and Re (mg / g)

[0172] stability starch Microcrystalline Cellulose Mannitol Sorbitol Month 0 41.5 41.9 42.8 39.6 Month 1 41.1 40.2 42.3 37.4 Month 2 39.5 38.8 42.1 36.5 Month 3 38.7 37.1 41.5 34.3 Month 6 36.2 36.5 40.4 30.7

[0173] Table 7 Effect of different excipients on ginsenoside Rb1 (mg / g)

[0174] stability starch Microcrystalline Cellulose Mannitol Sorbitol Month 0 38.5 38.6 39.2 38.8 Month 1 37.4 36.9 38.8 36.5 Month 2 36.3 36.1 37.7 34.3 Month 3 35.2 34.5 36.5 32.9 Month 6 33.7 32.2 34.3 29.8

[0175] Table 8 Effect of different excipients on the appearance of granules

[0176]

[0177]

[0178] As can be seen from Table 5-8, mannitol can achieve the best effect as auxiliary material, so the present invention selects mannitol as diluent. Traditional granule auxiliary materials include icing sugar starch, dextrin, sorbitol etc., but icing sugar has strong hygroscopicity, may interfere with effective ingredients, reduce curative effect, and granulation effect is not good, poor formability, easy to stick to sieve, patients such as diabetes, hypertension, obesity, coronary heart disease should not take for a long time; starch and dextrin are poorly water-soluble, have large hygroscopicity, poor stability, and have a large impact on granule storage; and all three can increase blood sugar, which is not suitable for diabetic patients. And the newly developed granule auxiliary material mannitol, all soluble in cold and hot water, itself has no hygroscopicity, will not affect the curative effect, good fluidity, large density, and the granule particle size prepared is more ideal, does not affect the content of effective substances and has a flavor correction function.

[0179] 3.7 Experimental selection of dosage of mannitol and dry cream

[0180] Table 9 Screening experiment of the dosage of mannitol and dry cream

[0181]

[0182]

[0183] As can be seen from Table 9, when the ratio of dry paste: mannitol is 1:1-2, the qualified rate of the granules, the shape of the granules, and the melting state of the granules are the best. The inventor believes that the reason why mannitol is better than other excipients may be that it has good solubility and stability. As a permeabilizing agent, it can also improve the taste, making patients more comfortable when taking it. When preparing dry paste granules, the addition of mannitol plays a role in its moisturizing properties, which helps prevent the granules from getting damp during storage and maintains its stability and effectiveness. It provides a new idea for the preparation of clinical Chinese medicine granules.

Claims

1. A medicine for diabetes, characterized in that: The medicine is composed of the following raw materials in parts by weight: 10-20 parts of astragalus, 10-20 parts of polygonatum, 5-15 parts of mulberry leaves, 5-15 parts of gynostemma pentaphyllum, 5-15 parts of stir-fried Shenqu, 3-9 parts of coptis root, 1-5 parts of panax notoginseng and 0.5-1.5 parts of cinnamon bark.

2. The drug according to claim 1, characterized in that The medicine is composed of the following raw materials in parts by weight: 15 parts of astragalus, 15 parts of polygonatum, 10 parts of mulberry leaves, 10 parts of gynostemma pentaphyllum, 10 parts of stir-fried Shenqu, 6 parts of coptis, 3 parts of panax notoginseng and 1 part of cinnamon.

3. A pharmaceutical preparation, characterized in that The pharmaceutical preparation comprises the drug according to any one of claims 1-2 and pharmaceutically acceptable excipients, and the preparation is selected from any one of granules, capsules, tablets, decoctions, oral liquids, pills or suppositories; the preparation is selected from granules.

4. The preparation according to claim 3, characterized in that The preparation process of the granules is as follows: (1) Take the raw material of claim 1 or 2, add 5 times the volume of ethanol for extraction, and use the filtrate for later use; (2) The filtrate of step (1) is dried under reduced pressure at 50-60° C. to obtain a dry paste, and then mannitol and a wetting agent are added, mixed evenly to obtain a soft material, sieved to obtain wet granules, dried, and sized to obtain granules.

5. The preparation according to claim 4, characterized in that In parts by weight, the ratio of the dry cream to mannitol is 1:1-2, preferably 1:1.

5.

6. The preparation according to claim 4, characterized in that The step (1) is to take the raw material of claim 1 or 2, add 5 times the volume of 50-70% ethanol, extract for 3 times, each time for 2 hours, and combine the filtrate for standby use.

7. The preparation according to claim 4, characterized in that The step (2) comprises drying the filtrate of step (1) under reduced pressure at 50-60° C. to obtain a dry paste with a relative density of 1.20-1.25, adding mannitol, and then adding 70% ethanol as a wetting agent, mixing evenly to prepare a soft material, passing through a 14-mesh sieve to prepare wet granules, drying at 60° C. for 1 hour, and sieving through a 20-mesh sieve to prepare the obtained granules.

8. The preparation according to claim 4, characterized in that The preparation process of the granules is as follows: (1) Take 15 parts of Astragalus, 15 parts of Polygonatum, 10 parts of Morus alba, 10 parts of Gynostemma pentaphyllum, 10 parts of Chao Shenqu, 6 parts of Coptis chinensis, 3 parts of Panax notoginseng, and 1 part of Cinnamon bark, add 5 times the volume of 60% ethanol and extract 3 times, each time for 2 hours, combine the filtrate and set aside; (2) Drying the filtrate under reduced pressure at 50-60° C. to obtain a dry paste with a relative density of 1.22, adding mannitol, and then adding 70% ethanol as a wetting agent, mixing them evenly to prepare a soft material, passing through a 14-mesh sieve to prepare wet granules, drying at 60° C. for 1 hour, and sieving through a 20-mesh sieve to prepare the resulting granules; wherein the ratio of the dry paste to mannitol is 1:1.

5.

9. Use of the drug according to any one of claims 1 to 2 in the preparation of a drug for preventing and treating diabetes.

10. The use according to claim 7, characterized in that The thirst-quenching disease is diabetes.

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