Composition for treating type 2 diabetes mellitus as well as preparation method and application thereof

Abstract

The invention provides a composition for treating type 2 diabetes mellitus as well as a preparation method and application thereof, and belongs to the technical field of prevention and treatment of type 2 diabetes mellitus. The composition for treating type 2 diabetes mellitus provided by the invention comprises radix ophiopogonis, schisandra chinensis, astragalus membranaceus, salvia miltiorrhiza, sugarcane leaves, oysters, radices trichosanthis, scalded leeches and red ginseng. Compared with traditional western medicines, the composition provided by the invention not only can stably reduce blood sugar, but also can improve insulin resistance and regulate blood fat, and can effectively treat type 2 diabetes mellitus and reduce the occurrence of diabetic complications. The compatibility of natural components of the composition reduces the risk of liver and kidney toxicity, and the composition is more suitable for long-term administration. The invention provides a safer and more comprehensive hypoglycemic product for patients.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of preventing and treating type 2 diabetes, and specifically relates to a composition for treating type 2 diabetes and a preparation method and application thereof. BACKGROUND

[0002] There are various types of drugs for treating type 2 diabetes, each with its unique mechanism of action, clinical advantages, and potential risks. Doctors usually develop individualized treatment plans based on patients' blood glucose levels, complication risks, economic conditions, and tolerability. The following are several commonly used types of hypoglycemic drugs and their analysis: (1) Metformin: Metformin is a first-line treatment for type 2 diabetes, with a low price and clear hypoglycemic effect, and can also improve insulin resistance and possibly reduce cardiovascular risk. However, about 30% of patients may experience gastrointestinal reactions such as nausea and diarrhea during the initial period of medication, and long-term use may affect the absorption of vitamin B12. In addition, patients with severely impaired renal function should avoid using metformin to prevent lactic acidosis. (2) SGLT-2 inhibitors: Significant heart and kidney protection, but increased risk of infection. SGLT-2 inhibitors such as dapagliflozin and empagliflozin can lower blood glucose by promoting urinary glucose excretion, and can also reduce cardiovascular events and delay kidney disease progression. However, this type of drug may increase the risk of urogenital system infections (such as urinary tract infections and vulvar pruritus), and may induce rare ketoacidosis, especially in patients with type 1 diabetes or extreme dieting. (3) GLP-1 receptor agonists: Strong hypoglycemic weight loss, but expensive and with significant side effects. GLP-1 receptor agonists such as semaglutide and liraglutide can not only significantly lower blood glucose, but also help patients lose weight and even reduce cardiovascular events. However, gastrointestinal reactions such as nausea and vomiting are relatively common, and some patients may stop taking the drug due to intolerance. In addition, this type of drug is expensive, and the long-term safety (such as the risk of thyroid tumors) still needs to be confirmed by more research. (4) Sulfonylureas: Strong hypoglycemic effect, but high risk of hypoglycemia. Sulfonylureas such as glimepiride and glipizide can effectively stimulate insulin secretion, have a strong hypoglycemic effect, and are relatively low in price. However, they can cause severe hypoglycemia, especially in older patients or those with impaired renal function, and long-term use may accelerate the decline of beta cell function. (5) Insulin: Most direct and effective, but requires injection and may cause weight gain. For patients with advanced type 2 diabetes, insulin is the most effective hypoglycemic means. However, insulin therapy is usually associated with weight gain and the risk of hypoglycemia, and frequent blood glucose monitoring is required, with poor patient compliance. (6) DPP-4 inhibitors: High safety, but limited hypoglycemic effect. DPP-4 inhibitors such as sitagliptin and vildagliptin have a low risk of hypoglycemia and are suitable for older patients, but have a limited hypoglycemic range and may increase the risk of pancreatitis (although rare).

[0003] With the continuous development of the field of diabetes treatment, western medicine has made significant progress in the effect of reducing blood sugar and protecting target organs, but there are still certain side effects and limitations in long-term use. Under this background, the unique advantages of traditional Chinese medicine have gradually attracted attention. However, there is currently a lack of a traditional Chinese medicine composition that can effectively treat type 2 diabetes. SUMMARY

[0004] Therefore, the purpose of the present application is to provide a composition for treating type 2 diabetes, which improves glucose metabolism through multi-target and overall regulation, while taking into account the effects of promoting blood circulation and dredging collaterals and regulating visceral functions, has a significant therapeutic effect on type 2 diabetes or diabetic complications, and has good clinical application prospects.

[0005] In order to achieve the above-mentioned purpose of the application, the present application provides the following technical solutions: The present application provides a composition for treating type 2 diabetes, comprising the following raw materials in parts by weight: Ophiopogon japonicus 6-12 parts, Schisandra chinensis 2-4 parts, Astragalus membranaceus 9-12 parts, Salvia miltiorrhiza 10-15 parts, sugarcane leaves 30-45 parts, Ostrea gigas 9-12 parts, Trichosanthes kirilowii 10-15 parts, Hirudo nipponia 1-3 parts, and Panax ginseng 3-6 parts.

[0006] The present application also provides a preparation method of the above-mentioned composition, comprising the following steps: mixing sugarcane leaves, Ostrea gigas, Ophiopogon japonicus, Schisandra chinensis, Astragalus membranaceus, and Salvia miltiorrhiza to obtain a mixture; mixing the mixture with water and decocting and extracting to obtain a decocting liquid; concentrating the decocting liquid to obtain a concentrate; mixing the concentrate with edible ethanol, standing, taking the supernatant, and concentrating to obtain a thick paste; mixing Hirudo nipponia, Trichosanthes kirilowii, and Panax ginseng, crushing to obtain a fine powder, mixing the fine powder with the thick paste, pill-making, and drying.

[0007] Preferably, the decocting and extracting is performed 1-3 times, the weight of water added each time is 6-10 times the weight of the mixture, and the decocting and extracting time each time is 0.5-1.5 h.

[0008] Preferably, when the decocting liquid is concentrated to obtain a concentrate, the concentrate has a relative density of 1.10-1.25 at 60-65℃; and when the supernatant is concentrated, the thick paste has a relative density of 1.30-1.45 at 60-65℃.

[0009] Preferably, the mass ratio of the concentrate to edible ethanol is 1:1; and the standing time is 36-54 h.

[0010] Preferably, the fine powder is a fine powder passing through an 80-120 mesh sieve.

[0011] Preferably, the pill-making comprises the following steps: mixing the fine powder with a mass percentage of 98-99% with thick paste, preparing soft material, extruding strip, preparing wet pill, spraying the prepared wet pill with ethanol solution with a volume fraction of 75-95% to wet, and scattering into the remaining fine powder, tumbling and polishing, and sieving pill.

[0012] Preferably, the tumbling and polishing time is 30-60 min; the upper sieve aperture is 5.0 mm, and the lower sieve aperture is 4.5 mm.

[0013] Preferably, the drying is 70-80 ℃ drying for 4-5 h.

[0014] The application further provides application of the composition or the preparation method in preparation of a drug for preventing and treating type 2 diabetes or diabetic complications.

[0015] The application has the following beneficial effects: Compared with traditional western medicine, the composition provided by the application can not only steadily reduce blood sugar, but also improve insulin resistance and regulate blood lipids, can effectively treat type 2 diabetes, and reduce the occurrence of diabetic complications. The compatibility of natural ingredients in the composition reduces the risk of liver and kidney toxicity, and is more suitable for long-term taking. The application provides a safer and more comprehensive blood sugar-lowering product for patients. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 Fig. 2 shows the effect of the composition of the application on the pancreas of type 2 diabetic rats (HE staining, x200), wherein the left picture in the first row from top to bottom is the result of the normal control group, and the right picture is the result of the model control group; the left picture in the second row is the result of the metformin group, and the right picture is the result of the composition of the application 3.7 g / kg group; the left picture in the third row is the result of the composition of the application 7.4 g / kg group, and the right picture is the result of the composition of the application 14.8 g / kg group. DETAILED DESCRIPTION

[0017] The application provides a composition for treating type 2 diabetes, comprising the following raw materials in terms of weight fraction: 6-12 parts of radix ophiopogonis, 2-4 parts of schisandra chinensis, 9-12 parts of radix astragali, 10-15 parts of salvia miltiorrhiza, 30-45 parts of sugarcane leaf, 9-12 parts of concha mactrae, 10-15 parts of radix trichosanthis, 1-3 parts of water leech, and 3-6 parts of red ginseng.

[0018] The application does not have special limitations on the specific sources of the above raw materials, and conventional commercially available products in the field can be used. In the application, the sugarcane leaf refers to the sugarcane leaf meeting the quality standard of Guangxi Zhuang Autonomous Region Yao Medicine, and preferably dry sugarcane leaf.

[0019] In the composition of the application, the relationship of monarch, minister, assistant and guide is as follows: Kung medicine: sugar cane leaves, heat and moisture, dry thirst, for diabetes Yin deficiency and dryness of the core pathogenesis, directly reduce sugar and nourish Yin; Huangqi, spleen, help gas to distribute moisture, both as Kung medicine, together with the effect of Yiqi Yangyin, heat and dryness.

[0020] Chen medicine: Maidong and Wuweizi, nourishing Yin and generating fluid, enhancing the nourishing Yin and reducing sugar effect of sugar cane leaves; Tianhuafen, heat and thirst, auxiliary sugar cane leaves clear heat; Danshen, promoting blood circulation and removing blood stasis, improving blood stasis syndrome of diabetes and preventing complications.

[0021] Zhu medicine: Oyster, Yang and astringent, prevent Yin liquid dispersion, and can also calm the mind; Red ginseng, tonifying qi and consolidating the root, preventing sugar cane leaves and Tianhuafen from damaging the spleen; hot water leech, removing blood stasis and dredging collaterals, improving microcirculation, assisting Danshen in promoting blood circulation.

[0022] Shi medicine: Wuweizi (also Shi), astringent and fluid, guiding drugs into liver and kidney, regulating the cold and warm nature of various drugs, making the whole prescription tonifying without stagnation, clearing without damaging the normal.

[0023] The composition of the application is also called Gantie Xiaodan Tongmai Pill. The whole prescription takes sugar cane leaves and Huangqi as Kung medicine, mainly benefiting qi and nourishing Yin. The Chen medicine helps to clear heat and generate fluid, promote blood circulation and dredge collaterals. The Zhu medicine takes into account astringency and prevents cold and cool damage to the normal. The Shi medicine regulates the nature of drugs. Together, they have the effects of benefiting qi and nourishing Yin, clearing heat and reducing dryness, promoting blood circulation and reducing sugar, and are suitable for type 2 diabetes with deficiency of both qi and Yin, dryness and blood stasis.

[0024] In the composition of the application, the Yao medicine sugar cane leaves are introduced, combined with a special compatibility relationship, which plays a synergistic effect. The composition of the application is designed according to the theory of Zhuang medicine, and systematically targets the complex pathogenesis of "deficiency of both qi and Yin and blood stasis and dryness". The core breakthrough is the introduction of agricultural waste - sugar cane leaves (included in the quality standard of Guangxi Yao medicine), which not only gives the prescription a distinct regional feature, but also transforms the by-products of Guangxi sugar cane industry into high-value medical resources, greatly improving the value of resource utilization. The sweet and cool nature of sugar cane leaves not only enhances the effect of nourishing Yin and clearing heat, but also significantly alleviates the warm and dry nature of red ginseng and Huangqi, making the whole prescription mild in nature and suitable for long-term use.

[0025] In the composition of the application, the amount of Maidong is preferably 7-11 parts, more preferably 8-10 parts; the amount of Wuweizi is preferably 3 parts; the amount of Huangqi is preferably 10-11 parts; the amount of Danshen is preferably 11-14 parts, more preferably 12-13 parts; the amount of sugar cane leaves is preferably 32-42 parts, more preferably 35-40 parts; the amount of oyster is preferably 10-11 parts, and the oyster is preferably raw oyster; the amount of Tianhuafen is preferably 11-14 parts, more preferably 12-13 parts; the amount of hot water leech is preferably 2 parts; the amount of red ginseng is preferably 4-5 parts.

[0026] The application further provides a preparation method of the composition, comprising the following steps: mixing sugarcane leaves, oysters, ophiopogon japonicus, schisandra chinensis, astragalus and salvia miltiorrhiza to obtain a mixture; mixing the mixture with water to extract by decocting, taking the decocting liquid to obtain a concentrate by concentration; mixing the concentrate with edible alcohol, standing, taking the supernatant to obtain a thick paste by concentration, and mixing hot-water leech, radix trichosanthis and red ginseng to obtain a fine powder by crushing, mixing the fine powder with the thick paste, pill-making and drying.

[0027] In the application, the number of times of decocting extraction is preferably 1-3, more preferably 2; the weight of water added each time is preferably 6-10 times the weight of the mixture, more preferably 7-9 times the weight of the mixture; and the time of decocting extraction each time is preferably 0.5-1.5 h, more preferably 0.8-1.2 h. In the application, when the decocting liquid is taken to obtain a concentrate by concentration, the relative density is preferably 1.10-1.25 (60-65 DEG C); and when the supernatant is taken to concentrate, the relative density is preferably 1.30-1.45 (60-65 DEG C). The application does not have special limitation to the specific way of concentration, and the conventional concentration way in the art can be adopted. In the application, the mass ratio of the concentrate to edible alcohol is preferably 1:1; and the standing time is preferably 36-54 h, more preferably 40-50 h.

[0028] The application does not have special limitation to the specific way of crushing, and the conventional crushing way in the art can be adopted. In the application, the fine powder is preferably a fine powder passing through a 80-120 mesh sieve, more preferably a fine powder passing through a 90-110 mesh sieve. In the application, the pill-making preferably comprises the following steps: mixing the fine powder with a mass percentage of 98%-99% with the thick paste to obtain soft material, extruding into strips, wet pill-making, spraying the prepared wet pill with an ethanol solution with a volume fraction of 75%-95% to wet, and scattering the remaining fine powder to roll, polish and sieve. The speed of wet pill-making is preferably 20-40 r / min; and when the remaining fine powder (referring to the remaining 1%-2% fine powder) is scattered, it is preferably scattered in several times. In the application, the rolling and polishing are preferably carried out in a rolling machine, and the time of rolling and polishing is preferably 30-60 min, more preferably 40-50 min; and the upper sieve aperture is preferably 5.0 mm, and the lower sieve aperture is preferably 4.5 mm. In the application, the drying is preferably carried out at 70-80 DEG C for 4-5 h.

[0029] The application further provides the use of the composition or the preparation method in the preparation of a drug for preventing and treating type 2 diabetes or diabetic complications.

[0030] The technical solutions provided by the application are described in detail below in combination with examples, but they should not be understood as limitations to the protection scope of the application.

[0031] In the following examples, the conventional methods are used unless otherwise specified.

[0032] The materials, reagents and the like used in the following examples can be obtained commercially unless otherwise specified.

[0033] Example 1 A composition for treating type 2 diabetes mellitus is made from the following raw materials: Ophiopogon japonicus 6g, Schisandra chinensis 2g, Astragalus membranaceus 9g, Salvia miltiorrhiza 10g, Saccharum officinarum 30g, Mactra veneriformis 9g, Radix Trichosanthis 10g, Hirudo nipponia 2g, Red ginseng 3g.

[0034] The preparation method is as follows: (1) Mix Saccharum officinarum, Mactra veneriformis, Ophiopogon japonicus, Schisandra chinensis, Astragalus membranaceus and Salvia miltiorrhiza to obtain a mixture; mix the mixture with water, heat and decoct and extract twice, each time adding 10 times the amount of water based on the weight of the mixture, decoct and extract for 1 hour each time, filter, and combine the two filtrates to obtain a decoction; concentrate the decoction to a concentrate with a relative density of 1.15 (60°C); mix the concentrate with an equal amount of edible ethanol thoroughly, stand for 48 hours, take the supernatant, and concentrate to a thick paste with a relative density of 1.35 (60°C), for standby use.

[0035] (2) Crush Radix Trichosanthis, Hirudo nipponia and Red ginseng, pass through an 80-mesh sieve, sterilize, and mix thoroughly to obtain a fine powder. Mix the thick paste with 99% of the fine powder based on the total weight of the fine powder, make soft material, extrude into strips, make wet pellets, and make pellets at a speed of 20 r / min. Place the prepared wet pellets in a pellet rolling machine, spray with an ethanol solution with a volume fraction of 75% to moisten, and alternately sprinkle the remaining 1% of the fine powder twice, roll and polish, take out after 30 minutes, sieve the pellets, sieve the upper sieve at 5.0 mm and the lower sieve at 4.5 mm, and place the sieved wet pellets in a 70°C oven to dry for 5 hours to obtain the composition pellets (also known as Ganglingxiaodongtongmai pellets).

[0036] Example 2 A composition for treating type 2 diabetes mellitus is made from the following raw materials: Ophiopogon japonicus 12g, Schisandra chinensis 4g, Astragalus membranaceus 12g, Salvia miltiorrhiza 15g, Saccharum officinarum 45g, Mactra veneriformis 12g, Radix Trichosanthis 15g, Hirudo nipponia 3g, Red ginseng 6g.

[0037] The preparation method is as follows: Mix Saccharum officinarum, Mactra veneriformis, Ophiopogon japonicus, Schisandra chinensis, Astragalus membranaceus and Salvia miltiorrhiza to obtain a mixture; mix the mixture with water, heat and decoct and extract once, adding 6 times the amount of water based on the weight of the mixture, decoct and extract for 0.5 hours, filter, and combine the two filtrates to obtain a decoction; concentrate the decoction to a concentrate with a relative density of 1.25 (65°C); mix the concentrate with an equal amount of edible ethanol thoroughly, stand for 36 hours, take the supernatant, and concentrate to a thick paste with a relative density of 1.45 (65°C), for standby use.

[0038] The blumea balsamifera, trichosanthes kirilowii and red ginseng are crushed, passed through a 120 mesh sieve, sterilized, and mixed to obtain fine powder. The thick paste is mixed with 98% of the fine powder by weight of the total fine powder to form soft material, which is extruded into strips, wet pellets are prepared at a speed of 40 r / min. The prepared wet pellets are placed in a pelletizer, sprayed with 95% ethanol solution to wet, and alternately sprinkled with the remaining 2% fine powder for 2 times, and then rolled and polished. After 60 min, the pellets are taken out, sieved, and the upper sieve is 5.0 mm and the lower sieve is 4.5 mm. The sieved wet pellets are placed in an oven at 80℃ for drying for 4 h to obtain the composition pellets (also known as Ganligexiandongtongmai pellets).

[0039] Example 3 A composition for treating type 2 diabetes is prepared from the following raw materials: ophiopogon 10g, schisandra 3g, astragalus 10g, salvia 13g, sugar cane leaf 40g, oyster 10g, trichosanthes kirilowii 13g, blumea balsamifera 2g, and red ginseng 4g.

[0040] The preparation method is as follows: The sugar cane leaf, oyster, ophiopogon, schisandra, astragalus, and salvia are mixed to obtain a mixture. The mixture is mixed with water, heated and decocted for extraction for 3 times, 8 times the weight of the mixture is added each time, decocted for extraction for 1.5 h, filtered, and the filtrates of the two times are combined to obtain a decoction. The decoction is concentrated into a concentrate with a relative density of 1.10 (60℃). The concentrate is fully stirred with an equal amount of edible ethanol, left to stand for 54 h, the supernatant is taken, and concentrated into a thick paste with a relative density of 1.30 (60℃) for standby.

[0041] The blumea balsamifera, trichosanthes kirilowii and red ginseng are crushed, passed through a 100 mesh sieve, sterilized, and mixed to obtain fine powder. The thick paste is mixed with 98% of the fine powder by weight of the total fine powder to form soft material, which is extruded into strips, wet pellets are prepared at a speed of 30 r / min. The prepared wet pellets are placed in a pelletizer, sprayed with 85% ethanol solution to wet, and alternately sprinkled with the remaining 2% fine powder for 2 times, and then rolled and polished. After 50 min, the pellets are taken out, sieved, and the upper sieve is 5.0 mm and the lower sieve is 4.5 mm. The sieved wet pellets are placed in an oven at 75℃ for drying for 4.5 h to obtain the composition pellets (also known as Ganligexiandongtongmai pellets).

[0042] Test Example 1 A single factor test is conducted on step (1) of the preparation method of Example 1 to investigate the effects of soaking time, decoction time, water amount, and decoction times on the quality of the composition. The dry extract rate of the medicinal liquid and the content of salvianolic acid B in salvia are used as evaluation indexes.

[0043] 1. Soaking time investigation The difference between the step (1) of the example 1 is that after obtaining the mixture, the water quantity is 8 times of the mixture weight each time, after adding water the first time, respectively soak 0, 0.5, 1.0, 1.5, 2.0 h, the rest is the same as the step (1) of the example 1, after combining the two filtrates, calculate the dry extract rate; at the same time, take the combined filtrate to determine the content of salvianolic acid B by liquid phase method. At the same time, carry out 3 parallel tests, the results are shown in table 1.

[0044] Table 1 soaking time investigation results (n=3)

[0045] From table 1, it can be seen that the increase of soaking time has little effect on the dry extract rate, and after the soaking time is more than 1 h, the content of salvianolic acid B is reduced, so the soaking time is not taken as the investigation factor of the decoction process optimization. Moreover, in the actual production, the medicinal material quantity is large, in order to save time and cost, the soaking time before decoction is determined as 0 h.

[0046] 2. Water quantity investigation The difference between the step (1) of the example 1 is that after obtaining the mixture, respectively add 6, 8, 10, 12 times of water, the rest is the same as the step (1) of the example 1. After combining the two filtrates, calculate the dry extract rate; at the same time, take the combined filtrate to determine the content of salvianolic acid B by liquid phase method. At the same time, carry out 3 parallel tests, the results are shown in table 2.

[0047] Table 2 water quantity investigation results (n=3)

[0048] From table 2, it can be seen that the change of water quantity has great effect on the dry extract rate and the total content of salvianolic acid B, after the water quantity reaches 10 times, the increase of dry extract rate tends to be flat, and the content gradually reduces. Therefore, the water quantity is selected as the investigation factor of the decoction process optimization, and the level is selected as 6-10 times.

[0049] 3. Decoction time investigation The difference between the step (1) of the example 1 is that after obtaining the mixture, respectively add 8 times of water, soak 0 h, after adding water the first time, heat and decoct twice, each time 0.5, 1.0, 1.5, 2.0 h, the rest is the same as the step (1) of the example 1. After combining the two filtrates, calculate the dry extract rate; at the same time, take the combined filtrate to determine the content of salvianolic acid B by liquid phase method. At the same time, carry out 3 parallel tests, the results are shown in table 3.

[0050] Table 3 decoction time investigation results (n=3)

[0051] As can be seen from Table 3, the increase of decocting time has great influence on the dry extract rate, and the increase of dry extract rate tends to be flat after the decocting time reaches 1.5 h, and the content is gradually reduced. Therefore, the time is selected as the investigation factor for the optimization of decocting process, and the level is selected as 0.5-1.5 h.

[0052] 4. Decoction times The difference from step (1) of Example 1 is that after obtaining the mixture, 8 times of water is added respectively, soaked for 0 h, and then heated and decocted for 1, 2 or 3 times respectively, each time for 1.0 h, and the rest is the same as step (1) of Example 1. After the three filtrates are combined, the dry extract rate is calculated; at the same time, the content of salvianolic acid B in the combined filtrate is determined by liquid phase method. Meanwhile, three parallel tests are carried out, and the results are shown in Table 4.

[0053] Table 4 Investigation results of decoction times (n=3)

[0054] As can be seen from Table 4, the increase of decoction times has great influence on the dry extract rate, and the increase of dry extract rate tends to be flat after the decoction times reaches 2 times, and the content is greatly reduced. Therefore, the decoction times is selected as the investigation factor for the optimization of decocting process, and the level is selected as 1-2 times.

[0055] Test Example 2 Effects of Ganlai Xiaoyan Tongmai Pills on type 2 diabetic rats Preparation of type 2 diabetic rat model: half of the healthy rats were taken, and after adaptive feeding for 3 d, high-fat and high-sugar feed was given. After feeding with high-fat and high-sugar feed for 4 weeks, the rats were fasted for 12 h without water, and then injected intraperitoneally (ip) with 35 mg / kg streptozotocin (STZ) citric acid buffer solution at one time. After 72 h, the tail of the mouse was cut to take blood, and the blood glucose was determined by blood glucose meter. The blood glucose >11.1 mmol / L was used as the success standard of modeling. Another 10 rats (as normal control group) were given ordinary feed for 4 weeks, and ip with the same amount of citric acid buffer solution at the same time.

[0056] Test method: the successfully modeled diabetic rats were randomly divided into model control group, metformin (71.4 mg / kg) group, and Ganlai Xiaoyan Tongmai Pills 3.7, 7.4 and 14.8 g / kg dose groups according to the blood glucose value, 10 rats in each group. The rats in the administration groups were given gavage administration at 10 ml / kg, and the normal control group and the model control group were given the same volume of distilled water, once a day, for 14 consecutive days. One hour after the last administration; the rats were fasted for 16 h without water, and the fasting blood glucose value was measured. The rats were anesthetized by intraperitoneal injection of 40 mg / kg sodium pentobarbital, the liver was taken, a small amount of liver tissue was weighed to measure the liver glycogen, and the pancreas was taken and preserved in 4% formaldehyde solution for histopathological examination.

[0057] Table 5 shows the results of fasting blood glucose levels in different groups. The fasting blood glucose levels in the model control group rats were elevated, showing a significant difference compared to the normal control group. p <0.01); Ganli Xiaodan Tongmai Pills were administered to rats by gavage at doses of 7.4 and 14.8 g / kg. After administration, fasting blood glucose levels were significantly reduced, showing a statistically significant difference compared to the model control group. p <0.05 or p <0.01).

[0058] Table 5. Effects of Ganli Xiaodan Tongmai Pills on Fasting Blood Glucose in Type 2 Diabetic Rats

[0059] Note: Compared with the normal control group, p <0.01; compared with the model control group, △ p <0.05; △△ p <0.01 The results of liver glycogen level detection in different groups are shown in Table 6. The liver glycogen content in the liver tissue of rats in the model control group was significantly reduced compared with the normal control group, showing a statistically significant difference. p <0.01); Ganli Xiaodan Tongmai Pills administered orally to diabetic rats at doses of 3.7, 7.4, and 14.8 g / kg increased liver glycogen content, showing a significant difference compared to the model control group. p <0.01).

[0060] Table 6. Effects of Ganli Xiaodan Tongmai Pills on Liver Glycogen in Type 2 Diabetic Rats

[0061] Note: Compared with the normal control group, p <0.01; compared with the model control group, △△ p <0.01 The results of the effects on the histopathological characteristics of the pancreas in type 2 diabetic rats are shown in the figure. Figure 1In normal pancreatic tissue, the surface of the pancreas is composed of a thin layer of loose connective tissue, with the capsule extending into the interlobular spaces. Blood vessels pass through the interlobular spaces, which are slightly wide. The glandular parenchyma consists of an exocrine and an endocrine portion. The exocrine portion comprises serous compound tubuloacinar glands with normal cell morphology. The endocrine portion consists of islets of Langerhans scattered within the lobules of the exocrine portion of the pancreas. The islets are abundant and show no obvious abnormalities. In the model group, mild fibrous connective tissue hyperplasia was observed in the exocrine portion of the glandular parenchyma, accompanied by significant inflammatory cell infiltration. Acinar atrophy and reduced volume were observed, with a small number of acinar cells showing vacuolar degeneration and small, round vacuoles visible in the cytoplasm. In the endocrine portion, islet cells showed vacuolar degeneration and round vacuoles in the cytoplasm, with some acinar cells entering the islets. The present invention, Ganli Xiaodan Tongmai Pill, administered to diabetic rats by gavage at doses of 3.7, 7.4 and 14.8 g / kg, can significantly reduce the proliferation of fibrous connective tissue and inflammatory cell infiltration in the exocrine part of the glandular parenchyma, reduce vacuolar degeneration of pancreatic islet cells, normalize cell morphology, and increase the number of islets.

[0062] Experimental Example 3 Effects of Ganli Xiaodan Tongmai Pills obtained in Example 1 on sleep in mice Fifty healthy mice, half male and half female, were randomly divided into three groups: a normal control group, an estazolam (0.41 g / kg) group, and three groups treated with Ganli Xiaodan Tongmai Pills at doses of 8.3, 16.6, and 33.2 g / kg, with ten mice in each group. Mice in the treatment groups were administered the drug via gavage at a dose of 20 mL / kg, while the normal control group received an equal volume of distilled water. This was done once daily for seven consecutive days. Forty minutes after the last gavage, the mice were observed for 5 minutes of spontaneous activity, including walking time and head lifting frequency. Mice that completed the spontaneous activity test were injected intraperitoneally with 38 mg / kg sodium pentobarbital solution. The mice's sleep status was observed (sleep was measured by the disappearance of the righting reflex; if a mouse could immediately right itself when placed in a supine position, and failed to do so for more than 60 seconds, the righting reflex was lost, and the mouse entered sleep). The time from the disappearance of the righting reflex to its recovery was defined as the mouse's sleep time. The number of mice falling asleep and the sleep time in each group were observed and recorded.

[0063] The results are shown in Tables 7 and 8. Gavage administration of Ganli Xiaodan Tongmai Pills at doses of 16.6 and 33.2 g / kg to mice reduced their walking time and head-raising frequency within 5 minutes, with statistically significant differences compared to the normal control group. p <0.01); Ganli Xiaodan Tongmai Pills administered to mice by gavage at a dose of 8.3 g / kg reduced the walking time of mice within 5 minutes, and the difference was statistically significant compared with the normal control group. p <0.01. Gavage administration of Ganli Xiaodan Tongmai Pills at doses of 16.6 and 33.2 g / kg to rats increased the rate of sleep onset and sleep duration in mice, with statistically significant differences compared to the normal control group. p <0.05 or p<0.01); the Ganlig Xiaoyan Tongmai Pill was administered to the rats at a dose of 8.3 g / kg by gavage, which could increase the sleep time of the mice, and the difference was statistically significant compared with the normal control group (P<0.01) p <0.05).

[0064] Table 7 Influence of the Ganlig Xiaoyan Tongmai Pill on the spontaneous activity of mice

[0065] Note: compared with the normal control group, p <0.05; p <0.01 Table 8 Influence of the Ganlig Xiaoyan Tongmai Pill on the hypnotic effect of subthreshold dose of sodium pentobarbital on mice

[0066] Note: compared with the normal control group, p <0.05; p <0.01 The above results show that the Ganlig Xiaoyan Tongmai Pill can indirectly assist in the treatment of type 2 diabetes and its complications by improving sleep. Modern medical research has confirmed that sleep disorders are closely related to the occurrence and development of type 2 diabetes. Insomnia and poor sleep quality can aggravate insulin resistance and affect blood glucose control. Traditional Chinese medicine theory also believes that "yang enters yin and sleeps", and diabetes (Xiaoyan) patients often have the pathogenesis of yin deficiency and yang hyperactivity, leading to insomnia. The Ganlig Xiaoyan Tongmai Pill has the effects of suppressing yang and calming the mind, and can improve the sleep state of patients by nourishing yin and suppressing yang, calming the heart and calming the mind, while treating type 2 diabetes. Good sleep can in turn promote blood glucose stability and complication prevention, forming a positive treatment cycle.

[0067] The above only describes the preferred embodiments of the present application, and it should be noted that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered within the protection scope of the present application.

Claims

1. A composition for treating type 2 diabetes, characterized by comprising, The composition comprises the following raw materials by weight: 6-12 parts of Ophiopogon japonicus, 2-4 parts of Schisandra chinensis, 9-12 parts of Astragalus membranaceus, 10-15 parts of Salvia miltiorrhiza, 30-45 parts of sugarcane leaves, 9-12 parts of oyster, 10-15 parts of Radix Trichosanthis, 1-3 parts of Hirudo nipponia, and 3-6 parts of red ginseng.

2. A process for the preparation of the composition of claim 1, characterized in that, The method comprises the following steps: mixing sugarcane leaves, oyster, Ophiopogon japonicus, Schisandra chinensis, Astragalus membranaceus and Salvia miltiorrhiza to obtain a mixture; mixing the mixture with water to extract by decoction, taking the decocted liquid to obtain a concentrate; mixing the concentrate with edible alcohol, standing, taking the supernatant to obtain a thick paste; mixing, crushing and powdering Radix Trichosanthis, Hirudo nipponia and red ginseng to obtain a fine powder, mixing the fine powder with the thick paste, pill-making and drying.

3. The production method according to claim 2, characterized by, The decoction extraction is performed for 1-3 times, and the weight of water added each time is 6-10 times the weight of the mixture, and the decoction extraction time is 0.5-1.5 h.

4. The production method according to claim 2, characterized by, When the decocted liquid is concentrated to obtain a concentrate, the concentrate is concentrated to have a relative density of 1.10-1.25 under the condition of 60-65°C; when the supernatant is concentrated, the thick paste is concentrated to have a relative density of 1.30-1.45 under the condition of 60-65°C.

5. The preparation method according to claim 2, characterized in that, The mass ratio of the concentrate to edible alcohol is 1:1, and the standing time is 36-54 h.

6. The preparation method according to claim 2, characterized in that, The fine powder is a fine powder passing through a 80-120 mesh sieve.

7. The preparation method according to claim 2, characterized in that, The pill-making comprises the following steps: mixing the fine powder with a mass percentage of 98-99% with the thick paste to obtain soft material, extruding strips, wet pill-making, spraying the prepared wet pills with an ethanol solution with a volume fraction of 75-95% to wet the pills, and scattering the remaining fine powder, tumbling and polishing, and sieving the pills.

8. The preparation method according to claim 7, characterized in that, The tumbling and polishing time is 30-60 min, the upper sieve aperture is 5.0 mm, and the lower sieve aperture is 4.5 mm.

9. The preparation method according to claim 2, characterized in that, The drying is performed at 70-80°C for 4-5 h.

10. Use of the composition of claim 1 or the preparation method of any one of claims 2-9 in the preparation of a drug for preventing and treating type 2 diabetes or diabetic complications.

Images