Use of xintong preparation in preparation of a medicine for treating diabetes and preparation method thereof

Abstract

The application discloses application of Xintong preparation in preparation of a medicine for treating diabetes and a preparation method thereof, and belongs to the field of traditional Chinese medicines. The Xintong preparation is prepared from 13 raw medicinal materials of Huangqi, Gegen, Danshen, Dangshen, Maidong, Heshouwu, Yinyanghuo, Dangui, Zaokesheng, Haizao, Kelp, Muli and Zhishi, has the effects of benefiting qi and activating blood, reducing phlegm and dredging collaterals. Pharmacodynamic experiments show that the Xintong preparation has the effect of reducing blood sugar, can effectively improve the physical conditions of polydipsia, polyphagia, polyuria and emaciation and lack of strength of an animal model of diabetes, significantly reduces the fasting blood sugar and serum insulin level, improves the oral glucose tolerance, has a definite treatment effect on type II diabetes, and expands the clinical application range of the Xintong preparation, and has a wide market application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to a new use of Xintong preparation, in particular to the application of Xintong preparation in the preparation of a drug for treating diabetes and a preparation method thereof, and belongs to the field of traditional Chinese medicines. BACKGROUND

[0002] Diabetes mellitus (DM) is a chronic metabolic disease, which is mainly characterized by abnormal blood glucose levels (hyperglycemia) in the blood, and further causes complications in associated organs, blood vessels and nerves. According to the report of the World Health Organization, the incidence of diabetes mellitus is increasing year by year worldwide, and diabetes mellitus will become the seventh leading cause of death in 2030. The International Diabetes Federation reports that 4.15 million people were affected by diabetes in 2017, and this number is expected to rise to 6.29 million by 2045.

[0003] Diabetes mellitus is divided into type I, type II, gestational diabetes and other types. Among them, type I diabetes is an autoimmune destruction of pancreatic beta cells, leading to absolute lack of insulin and causing nutritional metabolic abnormalities, accounting for 5% of clinical diabetes. Type I diabetes often causes patients to have polydipsia, polyphagia, polyuria and body wasting, that is, the clinical symptoms of "three more and one less". Sometimes it can cause acute severe metabolic disorders, infectious diseases, chronic complications and other related problems, and is more common in adolescents. Once diagnosed with type I diabetes, the patient needs to rely on exogenous insulin replacement therapy for life. Type II diabetes, also known as non-insulin-dependent diabetes mellitus, is mainly caused by insulin resistance and relative insulin secretion deficiency, and can occur at any age, mostly in adults. The onset is often insidious and easily ignored by patients. With uncontrolled blood glucose, various complications such as diabetic foot, diabetic nephropathy, retinopathy and the like will follow, which seriously endanger the life safety of patients. Reasonable control of diet is the fundamental way to control blood glucose, and oral hypoglycemic drugs are the preferred treatment. Gestational diabetes is a high blood sugar caused by different degrees of glucose intolerance and diabetes discovered or developed during pregnancy. The first choice is subcutaneous injection of insulin to reduce blood glucose to normal or near normal range, and oral hypoglycemic drugs are not recommended for the treatment of gestational diabetes to avoid affecting the normal development of the fetus.

[0004] At present, there is no drug that can completely cure diabetes, and reducing blood glucose and preventing complications are still effective means for treating diabetes. Western medicine treatment of type II diabetes mainly focuses on reducing blood glucose, and drugs such as sulfonylureas, glinides, biguanides and thiazolidinediones are often selected. However, long-term use will produce drug resistance and easily lose effectiveness, and the dosage and regimen need to be constantly adjusted. Long-term use of hypoglycemic drugs also puts a great burden on the liver and kidney of the patient, and drug accumulation can cause hypoglycemic poisoning, endangering the life safety of the patient.

[0005] Diabetes belongs to the category of "Xiaoke" in TCM. TCM believes that this disease is caused by yin deficiency and dryness-heat, and five internal organs weakness, which leads to the disease characterized by polydipsia, polyphagia, polyuria, gradual body weight loss, or turbid urine, sweet urine. The disease location of Xiaoke is mainly in the lung, spleen, stomach, kidney, especially in the kidney. TCM divides this disease into three stages of "upper Xiaoke, middle Xiaoke, and lower Xiaoke" for treatment. According to the pathogenesis characteristics of "yin deficiency as the root and dryness-heat as the branch", the treatment is to benefit qi and produce saliva, clear heat and moisten dryness, and to remove blood stasis for those with blood stasis. TCM treatment of diabetes focuses on diet combined with traditional Chinese medicine to coordinate and regulate. Compared with western medicine, traditional Chinese medicine has mild nature, can eliminate evil and support the healthy, smoothly reduce blood sugar, reduce blood sugar volatility, prevent the occurrence of hypoglycemic reaction, has low drug resistance, high safety, and significant effect in controlling blood sugar and preventing complications of diabetes.

[0006] CN1628837A discloses a Xintong preparation for treating coronary heart disease, angina pectoris and hyperlipidemia, which is made of 13 raw medicinal materials of Huangqi, Gegen, Danshen, Dangshen, Maidong, Huzhu, Yinyanghuo, Dangui, Zaojiaoci, Haizao, Kelp, Muli and Zhishi, has the effects of benefiting qi and tonifying kidney, softening and resolving hard masses, promoting blood circulation to remove blood stasis, resolving phlegm and dredging collaterals, is suitable for treating chest stuffiness, phlegm and blood stasis, heart pain, palpitation, chest distress, short breath, restlessness and fatigue, and is mainly used for treating coronary heart disease, angina pectoris and hyperlipidemia. Research shows that the Xintong preparation also has the functions of reducing blood sugar and maintaining the stability of blood sugar value. The drug name of the invention is Xintong granules (approval number: Guo Yao Zhun Zi Z20020098) and Xintong oral liquid (approval number: Guo Yao Zhun Zi Z10920014), and the product names of the above products are Qida Tong , which are all Chinese patent medicine products of Lunan Houpu Pharmaceutical Co., Ltd. SUMMARY

[0007] The purpose of the present application is to provide an application of the Xintong preparation in preparing a medicine for treating diabetes. The Xintong preparation is made of 13 raw medicinal materials of Huangqi, Gegen, Danshen, Dangshen, Maidong, Huzhu, Yinyanghuo, Dangui, Zaojiaoci, Haizao, Kelp, Muli and Zhishi, has the effects of benefiting qi and promoting blood circulation, and resolving phlegm and dredging collaterals. The application is found in the clinical application process of the Xintong preparation, and is confirmed by relevant pharmacodynamic tests to have great commercial value.

[0008] The diabetes of the present application is type II diabetes, especially the diabetes with TCM syndrome of deficiency of both qi and yin.

[0009] The Xintong preparation is made of the following Chinese medicinal components:

[0010]

[0011] Preferably, the Xintong preparation is made of the following components:

[0012]

[0013]

[0014] The traditional Chinese medicine described in the present application is used as raw material, different excipients are added, and different oral pharmaceutical preparations acceptable in clinic, such as granules, oral liquid, capsules and microcapsules, can be prepared from the traditional Chinese medicine components in the present application according to conventional processes.

[0015] It should be noted that the application described in the present application relies on the marketed product Xintong preparation, but the application of the present application is not limited to the above-mentioned preparation, and the Xintong preparation obtained by using the technical solutions of the present application can achieve the purpose of treating diabetes.

[0016] The preparation process of the Xintong preparation comprises the following steps:

[0017] A. Take 13 raw medicinal materials of Huangqi, Gegen, Danshen, Dangshen, Maidong, Huhu, Yinyanghuo, Dangui, Zaokesheng, Haizao, Kunkun, Muli and Zhishi, wherein Maidong, Yinyanghuo and Zhishi are selected, Dangshen, Haizao and Kunkun are selected and cut into segments, Huhu, Gegen and Muli are selected and cut into blocks, Huangqi, Dangui and Danshen are selected and cut into slices, and Zaokesheng is selected and crushed into fine powder for standby;

[0018] B. The Gegen and Danshen decoction pieces are weighed according to the prescription amount, 6-9 times the amount of 60%-80% ethanol is added, and refluxed for 2 times, each time for 1.5-2.5h, filtered, the filtrates are combined, and the alcohol extract I is obtained for standby, and the residue is obtained for standby;

[0019] C. 11 raw medicinal materials of Huangqi, Dangshen, Maidong, Huhu, Yinyanghuo, Dangui, Zaokesheng, Haizao, Kunkun, Muli and Zhishi are combined with the Gegen and Danshen residue obtained in step B, 6-9 times the amount of water is added for decoction, each time for 1.5-2.5h, the decoction liquids are combined, filtered, and the filtrate is concentrated under reduced pressure to the extract I with a relative density of 1.16-1.22 at 50-60℃;

[0020] D. The alcohol extract I obtained in step B and the extract I obtained in step C are combined, ethanol is added to make the alcohol content reach 60%-70%, and refrigerated for 24-48h, filtered, the filtrate is recovered with ethanol and concentrated under reduced pressure to the extract II with a relative density of 1.12-1.18 at 50-60℃ for standby;

[0021] E. The extract II obtained in step D is directly subjected to a conventional process or added with a pharmaceutically acceptable excipient to prepare an oral pharmaceutical preparation.

[0022] The preferred dosage form of the present application is granules, and the preparation method of the Xintong granules comprises the following steps:

[0023] A, take radix astragali, radix puerariae, salvia miltiorrhiza, codonopsis pilosula, ophiopogon japonicus, radix polygoni multiflori, epimedium, angelica sinensis, gleditsia sinensis, sea algae, laminaria japonica, ostrea and citrus aurantium 13 kinds of raw medicinal materials, wherein ophiopogon japonicus, epimedium and citrus aurantium are selected, codonopsis pilosula, sea algae and laminaria japonica are cut into segments after being selected, radix polygoni multiflori, angelica sinensis and salvia miltiorrhiza are cut into pieces after being selected, radix astragali, gleditsia sinensis and angelica sinensis are cut into slices after being selected, and gleditsia sinensis is crushed into fine powder after being selected, for standby;

[0024] B, the prescription amount of radix puerariae and salvia miltiorrhiza decoction pieces is taken, 8 times the amount of 70% ethanol is added, and refluxed for 2 times, 2h each time, filtered, and the filtrate is combined to obtain alcohol extract I for standby, and the residue is standby;

[0025] C, 11 kinds of raw medicinal materials of radix astragali, codonopsis pilosula, ophiopogon japonicus, radix polygoni multiflori, epimedium, angelica sinensis, gleditsia sinensis, sea algae, laminaria japonica, ostrea and citrus aurantium are combined with the residue of radix puerariae and salvia miltiorrhiza obtained in step B, 8 times the amount of water is added, and decocted for 2 times, 2h each time, the decoction liquid is combined, filtered, and the filtrate is concentrated under reduced pressure to 50-60 DEG C, the relative density of the extract I is 1.18;

[0026] D, the alcohol extract I obtained in step B and the extract I obtained in step C are combined, ethanol is added to make the alcohol content reach 65%, and refrigerated for 48h, filtered, the filtrate is recovered and concentrated under reduced pressure to 50-60 DEG C, the relative density of the extract II is 1.15, for standby;

[0027] E, the extract II obtained in step D is taken, and the belt vacuum drying is carried out, the powder is crushed, the heart Tong extract powder is obtained, the formula amount of sucrose powder: hydroxypropyl starch: mannitol = 5:3:1 mixture of auxiliary materials is added, mixed, granulated, dried, and the granules are made, that is, the heart Tong oral liquid is obtained.

[0028] Another preferred dosage form of the present application is oral liquid preparation, and the preparation method of the heart Tong oral liquid comprises the following steps:

[0029] A, take radix astragali, radix puerariae, salvia miltiorrhiza, codonopsis pilosula, ophiopogon japonicus, radix polygoni multiflori, epimedium, angelica sinensis, gleditsia sinensis, sea algae, laminaria japonica, ostrea and citrus aurantium 13 kinds of raw medicinal materials, wherein ophiopogon japonicus, epimedium and citrus aurantium are selected, codonopsis pilosula, sea algae and laminaria japonica are cut into segments after being selected, radix polygoni multiflori, angelica sinensis and salvia miltiorrhiza are cut into pieces after being selected, radix astragali, gleditsia sinensis and angelica sinensis are cut into slices after being selected, and gleditsia sinensis is crushed into fine powder after being selected, for standby;

[0030] B, the prescription amount of radix puerariae and salvia miltiorrhiza decoction pieces is taken, 8 times the amount of 70% ethanol is added, and refluxed for 2 times, 1.5h each time, filtered, and the filtrate is combined to obtain alcohol extract I for standby, and the residue is standby;

[0031] C. Take the prescribed amount of Radix Astragali, Radix Codonopsis, Radix Ophiopogonis, Radix Polygoni Multiflori, Herba Epimedii, Radix Angelicae Sinensis, Gleditsia sinensis, Sargassum, Ostrea gigas Thunb. and Citrus aurantium 11 raw medicinal materials and the residue of Radix Puerariae and Radix Salviae Miltiorrhizae obtained in step B, add 9 times the amount of water and decoct twice, each time for 1.5 h, combine the decoction liquid, filter, and reduce the pressure to concentrate the filtrate to 1000 mL of decoction concentrate I;

[0032] D. Take the decoction concentrate I obtained in step C and the alcohol extract I obtained in step B, add ethanol to make the alcohol content 60%, and refrigerate for 24 h, filter, recover the ethanol from the filtrate and reduce the pressure to concentrate to 870 mL, and refrigerate for standby;

[0033] E. Filter the refrigerated liquid obtained in step D, add 210 g of monosaccharide syrup, adjust the pH value to 7.0 with 20% sodium hydroxide solution, add water to 1000 mL, stir well, filter, fill and seal, sterilize, and obtain the product.

[0034] In order to achieve the above-mentioned dosage forms, it is necessary to add pharmaceutical excipients during the preparation of the above-mentioned dosage forms. These pharmaceutical excipients can include, but are not limited to, fillers, binders, preservatives, flavorings, humectants, matrix agents, disintegrants, and lubricants.

[0035] During the clinical application of Xintong preparation, the inventors found that Xintong preparation has the efficacy of treating diabetes. Pharmacodynamic tests show that Xintong preparation is an effective formula for treating diabetes, can reduce blood glucose, can effectively improve the physical conditions of polydipsia, polyphagia, polyuria and emaciation of animal models of diabetes, significantly reduce fasting blood glucose and serum insulin levels, improve oral glucose tolerance, and have a definite therapeutic effect on type II diabetes. It provides a new choice for clinical medication, and embodies the curative effect characteristics of traditional Chinese medicine with overall, multi-target and multi-component synergistic action.

[0036] Based on the feedback of the clinical use of Xintong granules and Xintong oral liquid, the inventors have carried out a series of researches on the application of Xintong granules and Xintong oral liquid in the treatment of type II diabetes. In order to verify the effect of Xintong preparation of the present application in treating type II diabetes, the inventors have carried out corresponding animal experiment research. It should be noted that the samples obtained by the representative formula and the preparation method of the present application are selected for the animal experiment research. Due to the limitation of the space, the tests and results involved in the products obtained by other formulas and preparation methods of the present application are not listed one by one.

[0037] Experimental Example 1: Influence of Xintong Granules on the Body Weight and Blood Glucose Value of Type II Diabetes Model Rats

[0038] 1. Experimental materials

[0039] 1.1. Experimental animals and feed

[0040] SPF level SD rats, half male and half female, 60, weight (200 ± 20) g, provided by LuNan Pharmaceutical Group Co., Ltd., experimental animal license number: SYXK (Lu) 20180008. Before the experiment, adapt to the clean level animal laboratory for 1 week, male and female separately, room temperature 20-25℃, relative humidity 40%-60%, natural light, free food, water.

[0041] 1.2 Instruments, reagents and drugs

[0042] AG285 type electronic analytical balance (Mettler-Toledo, Switzerland); streptozotocin aqueous solution (Shanghai Fushen Biotechnology Co., Ltd.); the test drug is Xintong granules obtained in Example 3, and the positive control drug is Shenqi Jiangtang granules (batch number Z10950075, LuNan Hupu Pharmaceutical Co., Ltd.).

[0043] 2 Method

[0044] 2.1 Modeling and grouping administration

[0045] Take 60 SPF level SD rats, and randomly divide them into 6 groups, namely normal control group, model control group, Shenqi Jiangtang granules positive control group (referred to as "positive control group"), Xintong granules high-dose group (referred to as "test high-dose group"), Xintong granules medium-dose group (referred to as "test medium-dose group") and Xintong granules low-dose group (referred to as "test low-dose group"), 10 in each group, half male and half female.

[0046] Except for the normal control group, the other groups of rats were first habitually fed with conventional feed for 7 days, and then induced to be fed with high-fat and high-sugar (20% lard oil, 20% white sugar) feed for 45 days. After fasting for 24 hours, they were injected with 2% streptozotocin aqueous solution (160 mg / kg of rat weight) through the abdominal cavity within one week, and after 7 days, they were fasted for 12 hours, the tail tip was taken to blood, and the fasting blood glucose value was measured by blood glucose meter. The rats with blood glucose level reaching 11-30 mmol / L were the type II diabetes animal models.

[0047] 2.2 Administration

[0048] After modeling, each group was administered by gavage. According to the dose conversion coefficient of different animals in the appendix of the "Guiding Principles for Clinical Research of New Drugs of Traditional Chinese Medicine", the positive control group was given Shenqi Jiangtang granules 0.95 g / kg by gavage, the test high-dose, medium-dose and low-dose groups were given Xintong granules (4.41 g / kg, 2.21 g / kg, 1.10 g / kg) by gavage, which were equivalent to 2 times, 1 time and 0.5 times the human equivalent dose, respectively. The normal control group and the model control group were given the same volume of normal saline by gavage, once a day, for 7 consecutive days.

[0049] 2.3 Detection index and method

[0050] 2.3.1 Observation of the overall condition of rats

[0051] During the experiment, the physiological activity status of rats in each group was recorded, including changes in diet, urination frequency and body weight, and the condition of rats in each group was observed.

[0052] 2.3.2 Detection of blood glucose levels in rats

[0053] Blood was collected from the tail tip of rats in each group, and their fasting blood glucose levels were measured and recorded using a blood glucose meter.

[0054] 2.4 Statistical Analysis

[0055] SPSS 19.0 statistical software was used for analysis. Experimental data are expressed as mean ± standard deviation. The results were expressed in the form of “…”. One-way ANOVA was used for comparisons among multiple groups, and a p-value < 0.05 was considered statistically significant.

[0056] 3 Results

[0057] 3.1 Effects of the drug on the physiological activity and body weight of type II diabetic rats

[0058] Compared with the normal control group, the rats in the model control group had significantly lower body weight (P < 0.05), significantly increased food intake and urination frequency, and external manifestations included decreased activity frequency, lethargy, slow movement, and emaciation, indicating successful model establishment. Compared with the model control group, the effects of the positive control group and the high, medium, and low dose groups on the increase in body weight were as follows: high dose group > positive control group > medium dose group > low dose group. The rats' food intake, urination frequency, and external manifestations gradually approached those of the normal group, and the differences were all statistically significant (P < 0.05). The experiment shows that Xintong granules have a significant effect on improving body weight in type II diabetic rats. The results are shown in Table 1.

[0059] Table 1. Effects of Xintong Granules on Body Weight in Type II Diabetic Rats n=10)

[0060]

[0061] Note: Compared with the normal control group: P < 0.05 is indicated by "△"; compared with the model control group: P < 0.05 is indicated by "*".

[0062] 3.2 Effects of the drug on blood glucose levels in type II diabetic rats

[0063] Compared with the normal control group, the blood glucose value of the model control group was significantly increased, and the difference was statistically significant (P<0.05), indicating that the modeling was successful; compared with the model control group, the influence of the positive control group and the test high, medium and low dose groups on the decrease of the blood glucose value of the rats was in turn: test high dose group > positive control group > test medium dose group > test low dose group, and the differences were statistically significant (P<0.05), and the experiment showed that Xintong granules had obvious hypoglycemic effect on type II diabetic rats. The results are shown in Table 2.

[0064] Table 2 Influence of Xintong granules on blood glucose value of diabetic rats n=10

[0065]

[0066] Note: Compared with the normal control group, P<0.05, represented by "△"; compared with the model control group, P<0.05, represented by "*".

[0067] Example 2 Influence of Xintong granules on water intake, food intake and glucose tolerance of type II diabetic model mice

[0068] 1 Experimental materials

[0069] 1.1 Experimental animals

[0070] 60 male SPF C57BL / 6J mice, 6-8 weeks old, weighing 20±4 g, were provided by Lunan Pharmaceutical Co., Ltd., experimental animal license number: SYXK(Lu)20180008. The animals were adaptively fed in a clean level animal laboratory for 1 week before the experiment, the room temperature was 20-25℃, the relative humidity was 40%-60%, the natural light, and the animals were free to drink water and eat food.

[0071] 1.2 Instruments, reagents and drugs

[0072] One-Touch Ultra blood glucose meter (Johnson & Johnson, USA); One-Touch blood glucose test paper (Johnson & Johnson, USA); Glucose oxidase method blood glucose determination kit (Shanghai Rongsheng Biological Medicine Co., Ltd.); Mouse Insulin (INS) Elisa assay kit (Nanjing Jiancheng Biological Technology Co., Ltd.); Tetraoxypyrimidine (Japan and light pharmaceutical industry Co., Ltd.); Glucose (analytical pure) (Tianjin Fenshen Chemical Reagent Technology Co., Ltd.); The test drug is Xintong granules obtained in Example 3, and the positive control drug is Shenqi Jiangtang granules (batch number Z10950075, Lunan Hupu Pharmaceutical Co., Ltd.).

[0073] 2 Experimental method

[0074] 2.1 Modeling

[0075] Take 60 C57BL / 6J mice, after fasting for 12 hours, intraperitoneal injection of four oxygen pyrimidine (2% four oxygen pyrimidine solution prepared with sterile saline) at a dose of 250 mg / kg. To prevent the death of mice, 4.5-5 hours after intraperitoneal injection, the mice were given 50% glucose solution by gavage, with a dose of 20 mL / kg body weight. Only eat during modeling, after modeling for one week, take the tail vein blood to detect fasting blood glucose, with blood glucose above 11.1 mmol / L mice as diabetic model mice, the whole performance of the model animals show "three more and less", the model mice into the pharmacological experiment of the application.

[0076] 2.2 Grouping and administration

[0077] Take 60 C57BL / 6J mice, randomly divided into the following 6 groups, namely normal control group, model control group, Shenqi Jiangtang granules positive control group (referred to as "positive control group"), Xintong granules low dose group (referred to as "test low dose group"), Xintong granules medium dose group (referred to as "test medium dose group") and Xintong granules high dose group (referred to as "test high dose group"), 10 in each group.

[0078] After modeling, each group was given gavage, according to the dose conversion coefficient of different animals in the appendix of "Guiding Principles for Clinical Research of New Drugs of Traditional Chinese Medicine", the positive control group was given Shenqi Jiangtang granules 1.37 g / kg by gavage, the test high, medium and low dose groups were given Xintong granules (6.38 g / kg, 3.19 g / kg, 1.60 g / kg) by gavage, which was equivalent to 2 times, 1 times and 0.5 times the human equivalent dose, the normal control group and the model control group were given the same volume of normal saline by gavage, once a day, for 14 days.

[0079] 2.3 Detection index and method

[0080] 2.3.1 Collection of blood samples

[0081] The mice were sampled before the end of the last experiment, and were fasted and not watered at 8 pm the day before. At 8 am the next day, the mice were taken out of the eye and blood was collected. The blood of each mouse was collected in a 2 mL centrifuge tube. After collection, the blood was allowed to stand for 30 min, and then centrifuged at 4°C at 4000 r / min for 7 min using a low-temperature table centrifuge. The serum was transferred to a new centrifuge tube and immediately stored in a -80°C freezer for subsequent index detection.

[0082] 2.3.2 Blood glucose detection

[0083] Fasting blood glucose measurement method: after changing cage at 8pm, the mice were fasted but allowed free access to water, until 8am on the second day, for a total of 12h fasting. Tail blood was collected and blood glucose was measured using the One-Touch Ultra steady plus blood glucose meter and test strips from Johnson & Johnson, once every 2 weeks. The last fasting blood glucose measurement was performed before the mice were sacrificed.

[0084] 2.3.3 Oral glucose tolerance test (OGTT)

[0085] OGTT was performed 3 days before the mice were sacrificed. The mice were given a 50% glucose solution by gavage. The tail vein blood glucose of the mice was measured using the Johnson One-Touch Ultra steady plus blood glucose meter, and was marked as 0 before gavage, and the blood glucose was detected at 30, 60 and 120 min after gavage and recorded. The OGTT result curve was plotted with the time of blood glucose test as the horizontal coordinate and the blood glucose value of the mice as the vertical coordinate, and the area under the curve (AUC) was calculated to compare the changes in the effects of the traditional Chinese medicine intervention groups.

[0086] AUC = 15 x (0 min blood glucose value) + 30 x (30 min blood glucose value) + 45 x (60 min blood glucose value) + 30 x (120 min blood glucose value)

[0087] 2.3.4 Fasting serum insulin detection

[0088] The Mouse Insulin (INS) Elisa assay kit was used to measure the serum insulin level according to the requirements of the kit instructions.

[0089] ① Preparation: The kit was equilibrated at room temperature for about 5 min to prevent antibody degradation. The enzyme-linked conjugate and sample were prepared for rewarming. And enough enzyme-labeled plate, standard and sample were prepared as needed.

[0090] ② Sample addition: Blank wells (blank control wells without sample and enzyme-labeled reagent, the same for the rest of the steps), standard wells and sample wells were set up. The standard wells in the enzyme-labeled coated plate were added with 25 μL of standard 1-5 with high to low concentration from the kit, and 25 μL of serum was added to each sample well. Then 100 μL of enzyme-linked conjugate was added to each well.

[0091] ③ Incubation: Incubate at room temperature on a horizontal shaker at 700-900 rpm for 2h, without needing to seal the plate film.

[0092] ④ Liquid preparation: The 21-fold concentrated washing solution was diluted with distilled water to 1 x washing solution for standby use.

[0093] ⑤ Washing: Discard the liquid, spin dry, add full washing solution to each well, stand for 30s, then discard, repeat 5 times, and pat dry.

[0094] ⑥Add enzyme: add 200 μL TMB substrate to each well except blank wells, and incubate at room temperature for 15 min.

[0095] ⑦Stop: add 500 μL stop solution to each well to stop the reaction (at this time, the color changes from blue to yellow), and mix well on a horizontal shaker for about 5 s.

[0096] ⑧Determination: adjust the zero with the blank wells, and measure the absorbance (OD value) of each well at 450 nm within 30 min after adding the stop solution.

[0097] 2.4 Statistical processing

[0098] The experimental data were expressed in the form of "mean ± standard deviation" by using SPSS 19.0 statistical software. One-way ANOVA was used for comparison among multiple groups, and P<0.05 indicated that the difference was statistically significant.

[0099] 3 Results

[0100] 3.1 Observation of the living state of mice

[0101] The mice in the normal control group were normal, with bright fur, frequent activity, and normal water and food intake. The mice in the diabetic model control group gradually lost weight, with greasy and easily falling fur, decreased luster, listlessness, and polyuria. After being administered with Xintong Granules, the mice showed improved greasy fur, increased luster, increased weight, reduced urine output, and relatively drier bedding.

[0102] 3.2 Changes in food intake of mice

[0103] The results showed that compared with the normal control group, the food intake of the mice in the model control group was significantly increased, and the difference was statistically significant (P<0.05), indicating that the modeling was successful. Compared with the model control group, both the Shenqi Jiangtang and Xintong Granules groups could significantly inhibit the food intake of the mice (P<0.05), and the inhibitory effect of the high-dose Xintong Granules was even higher than that of the Shenqi Jiangtang positive control. The results are shown in Table 3.

[0104] Table 3 Effect of Xintong Granules on food intake of diabetic mice n=10

[0105]

[0106]

[0107] Note: P<0.05 is indicated by "△" compared with the normal control group; P<0.05 is indicated by "*" compared with the model control group.

[0108] ​3.3 Changes in water intake of mice

[0109] The results showed that compared with the normal control group, the water intake of mice in the model control group was significantly increased, and the difference was statistically significant (P<0.05), indicating that the modeling was successful; compared with the model control group, the Shenqi Jiangtang and different doses of Xintong granules groups could significantly inhibit the water intake of mice (P<0.05), especially the high-dose Xintong granules, which had a higher inhibitory effect on the water intake of diabetic mice than the Shenqi Jiangtang positive control. The results are shown in Table 4.

[0110] Table 4 Effect of Xintong granules on water intake of diabetic mice n=10

[0111]

[0112] Note: Compared with the normal control group, P<0.05 is represented by “△”; compared with the model control group, P<0.05 is represented by “*”.

[0113] 3.4 Results of fasting blood glucose monitoring

[0114] The results showed that compared with the normal control group, the blood glucose detection results of mice in the model control group at 7d and 14d were different (P<0.05), indicating that the modeling was successful. After 2 weeks of drug intervention, the blood glucose values of mice showed differences, and compared with the model control group, after intragastric administration of different doses of Xintong granules, the blood glucose values at 7d and 14d were significantly reduced (P<0.05), and the hypoglycemic effect was similar to that of the positive control, indicating that low, medium and high doses of Xintong granules had a hypoglycemic effect on type II diabetic mice. The results are shown in Table 5.

[0115] Table 5 Effect of Xintong granules on fasting blood glucose values of diabetic mice n=10

[0116]

[0117]

[0118] Note: Compared with the normal control group, P<0.05 is represented by “△”; compared with the model control group, P<0.05 is represented by “*”.

[0119] 3.5 Results of oral glucose tolerance test (OGTT)

[0120] The results showed that compared with the normal control group, the blood glucose peak of the model control group was significantly increased, the overall blood glucose curve was higher, and the blood glucose decreased slowly, and the blood glucose at 120 min was still much higher than that before gavage, indicating that the modeling was successful. Compared with the model control group, the blood glucose of mice was decreased after gavage of Shenqi Jiangtang or Xintong granules, and the blood glucose of mice basically returned to the level before gavage after gavage of high-dose Xintong granules for 2 h.

[0121] According to the area under the blood glucose curve (AUC) data, compared with the normal control group, the area under the blood glucose curve of the model control group was significantly increased, and the difference was statistically significant (P<0.05); compared with the model control group, the AUC value of all drug groups was lower than that of the model control group, and the difference was statistically significant (P<0.05). The results are shown in Table 6.

[0122] Table 6 Effect of Xintong granules on oral glucose tolerance of diabetic mice n=10

[0123]

[0124] Note: Compared with the normal control group, P<0.05 represented by “△”; compared with the model control group, P<0.05 represented by “*”.

[0125] 3.6 Fasting serum insulin detection results

[0126] The results showed that compared with the normal control group, the fasting serum insulin level of the model control group was significantly increased (P<0.05), indicating that the modeling was successful. Compared with the model control group, after gavage of different doses of Xintong granules, the fasting serum insulin level was significantly decreased (P<0.05), indicating that low, medium and high doses of Xintong granules had the effect of reducing serum insulin in type II diabetic mice. The results are shown in Table 7.

[0127] Table 7 Effect of Xintong granules on fasting serum insulin level of diabetic mice n=10

[0128]

[0129]

[0130] Note: Compared with the normal control group, P<0.05 represented by “△”; compared with the model control group, P<0.05 represented by “*”.

[0131] The pharmacodynamic experiment results show that the heart-passing preparation has the blood sugar reducing effect, can effectively improve the polyuria, polydipsia, polyphagia and emaciation and other physical conditions of the diabetes model animals, significantly reduces the fasting blood sugar and serum insulin level, improves the oral glucose tolerance, and has the definite treatment effect on the type II diabetes. DETAILED DESCRIPTION

[0132] In order to make the skilled in the art fully understand the present application, the present application is further illustrated by specific examples below, but the skilled in the art should know that the present application examples do not limit the present application in any way.

[0133] Example 1 Preparation of heart-passing oral liquid

[0134]

[0135] A, take 13 kinds of medicinal materials of Huangqi, Gegen, Danshen, Dangshen, Maidong, Huhu, Yinyanghuo, Dangui, Zaocongshi, Haizao, Kelp, Muli and Zhishi, wherein Maidong, Yinyanghuo and Zhishi are selected, Dangshen, Haizao and Kelp are cut into segments after being selected, Huhu, Gegen and Muli are cut into blocks after being selected, Huangqi, Dangui and Danshen are cut into slices after being selected, and Zaocongshi is crushed into fine powder after being selected, for standby use;

[0136] B, Gegen and Danshen decoction pieces are weighed according to the prescription amount, 6 times 80% ethanol is added for refluxing 2 times, 1.5h each time, filtered, the filtrates are combined to obtain alcohol extract I for standby use, and the residues are standby use;

[0137] C, 11 kinds of raw medicinal materials of Huangqi, Dangshen, Maidong, Huhu, Yinyanghuo, Dangui, Zaocongshi, Haizao, Kelp, Muli and Zhishi and the residues of Gegen and Danshen obtained in step B are combined, 9 times water is added for decocting 2 times, 2.5h each time, the decocting liquids are combined, filtered, and the filtrate is concentrated under reduced pressure to 50-60℃ when the relative density of the extract I is 1.21;

[0138] D, the alcohol extract I obtained in step B and the extract II obtained in step C are combined, ethanol is added to make the alcohol content reach 60%, and the mixture is refrigerated for 36h, filtered, the filtrate is recovered for ethanol and concentrated under reduced pressure to 50-60℃ when the relative density of the extract II is 1.17, for standby use;

[0139] E, the extract II obtained in step D is taken, 4 times purified water is added to stir uniformly to obtain water extract, the water extract is filtered, 1g activated carbon is added to each 100mL filtrate, heated to 80℃ for 60min, filtered to remove the carbon, purified water is added to the total amount, the pH is adjusted to 7.5, 0.5g β-cyclodextrin is added to each 100mL liquid, the inclusion temperature is controlled to 40℃, and the inclusion is performed for 60min, filtered, purified water is added to the total amount, filtered to the qualified clarity, filled, sterilized, and packaged.

[0140] Example 2 Preparation of heart-passing capsule

[0141]

[0142] A, take radix astragali, radix puerariae, salvia miltiorrhiza, codonopsis pilosula, radix ophiopogonis, radix polygoni multiflori, epimedium, angelica sinensis, gleditsia sinensis, sea algae, laminaria japonica, ostrea and citrus aurantium 13 kinds of medicinal materials, among which radix ophiopogonis, epimedium and citrus aurantium are selected, codonopsis pilosula and sea algae are cut into segments after being selected, radix polygoni multiflori, radix puerariae and ostrea are cut into blocks after being selected, radix astragali, angelica sinensis and salvia miltiorrhiza are cut into slices after being selected, and gleditsia sinensis is crushed into fine powder after being selected, for standby;

[0143] B, the radix puerariae and salvia miltiorrhiza decoction pieces are weighed according to the prescription amount, 9 times the amount of 60% ethanol is added and refluxed for 2 times, 1.5h each time, filtered, and the filtrate is combined to obtain alcohol extract I for standby, and the residue is standby;

[0144] C, 11 kinds of raw materials of radix astragali, codonopsis pilosula, radix ophiopogonis, radix polygoni multiflori, epimedium, angelica sinensis, gleditsia sinensis, sea algae, laminaria japonica, ostrea and citrus aurantium and the radix puerariae and salvia miltiorrhiza residue obtained in step B are combined, 6 times the amount of water is added and decocted for 2 times, 1.5h each time, the decoction liquid is combined, filtered, and the filtrate is concentrated under reduced pressure to 50-60℃ when the relative density of the extract I is 1.20;

[0145] D, the alcohol extract I obtained in step B and the extract II obtained in step C are combined, ethanol is added to make the alcohol content reach 70%, and refrigerated for 24h, filtered, the filtrate is recovered and concentrated under reduced pressure to 50-60℃ when the relative density of the extract II is 1.13, for standby;

[0146] E, the extract II obtained in step D is vacuum dried under the condition of vacuum degree-0.09MPa--0.10Mpa and drying temperature 63℃, crushed to obtain Xintong extract powder, and the formula amount of starch, micronized silica gel and low-substituted hydroxypropyl cellulose (weight ratio 5:2:1) is added, mixed, granulated, dried, and whole granulated, filled, polished in a polishing machine, and the broken capsules are removed, to obtain the product.

[0147] Preparation of Xintong granules

[0148]

[0149] A, take radix astragali, radix puerariae, salvia miltiorrhiza, codonopsis pilosula, radix ophiopogonis, radix polygoni multiflori, epimedium, angelica sinensis, gleditsia sinensis, sea algae, laminaria japonica, ostrea and citrus aurantium 13 kinds of medicinal materials, among which radix ophiopogonis, epimedium and citrus aurantium are selected, codonopsis pilosula and sea algae are cut into segments after being selected, radix polygoni multiflori, radix puerariae and ostrea are cut into blocks after being selected, radix astragali, angelica sinensis and salvia miltiorrhiza are cut into slices after being selected, and gleditsia sinensis is crushed into fine powder after being selected, for standby;

[0150] B, the radix puerariae and salvia miltiorrhiza decoction pieces are weighed according to the prescription amount, 9 times the amount of 60% ethanol is added and refluxed for 2 times, 1.5h each time, filtered, and the filtrate is combined to obtain alcohol extract I for standby, and the residue is standby;

[0151] C, the prescription amount of Astragalus, Dangshen, Ophiopogon, Radix Polygoni Multiflori, Herba Epimedii, Angelica, Gleditsia sinensis, Sargassum, Oyster and Citrus aurantium 11 kinds of raw medicinal materials are weighed and combined with the residues of Pueraria and Salvia miltiorrhiza obtained in step B, 8 times the amount of water is added and decocted for 2 times, each for 2 hours, the decoction liquid is combined, filtered, and the filtrate is reduced pressure concentrated to the extract I with relative density of 1.18 at 50-60°C;

[0152] D, the alcohol extract I obtained in step B and the extract I obtained in step C are combined, ethanol is added to make the alcohol content reach 65%, and refrigerated for 48 hours, filtered, and the filtrate is recovered by ethanol and reduced pressure concentrated to the extract II with relative density of 1.15 at 50-60°C, for standby;

[0153] E, the extract II obtained in step D is taken, and the vacuum belt drying is carried out, and the fine powder of Xintong extract is obtained by crushing, adding the formula amount of sucrose powder: hydroxypropyl starch: mannitol = 5:3:1 mixture of auxiliary materials, mixing evenly, granulating, drying, and whole granulating, to obtain the product.

[0154] Preparation of Xintong Capsules

[0155]

[0156] A, 13 kinds of medicinal materials of Astragalus, Pueraria, Salvia miltiorrhiza, Dangshen, Ophiopogon, Radix Polygoni Multiflori, Herba Epimedii, Angelica, Gleditsia sinensis, Sargassum, Oyster and Citrus aurantium are taken, Ophiopogon, Herba Epimedii and Citrus aurantium are selected, Dangshen, Sargassum and Kelp are cut into sections, Radix Polygoni Multiflori, Pueraria and Oyster are cut into blocks, Astragalus, Angelica and Salvia miltiorrhiza are cut into slices, and Gleditsia sinensis is crushed into fine powder for standby;

[0157] B, the prescription amount of Pueraria and Salvia miltiorrhiza decoction pieces is weighed, 8 times the amount of 70% ethanol is added and refluxed for 2 times, each for 2.5 hours, filtered, and the filtrate is combined to obtain alcohol extract I for standby, and the residue is standby;

[0158] C, 11 kinds of raw medicinal materials of Astragalus, Dangshen, Ophiopogon, Radix Polygoni Multiflori, Herba Epimedii, Angelica, Gleditsia sinensis, Sargassum, Oyster and Citrus aurantium are weighed and combined with the residues of Pueraria and Salvia miltiorrhiza obtained in step B, 7 times the amount of water is added and decocted for 2 times, each for 1.5 hours, the decoction liquid is combined, filtered, and the filtrate is reduced pressure concentrated to the extract I with relative density of 1.22 at 50-60°C;

[0159] D, the alcohol extract I obtained in step B and the extract I obtained in step C are combined, ethanol is added to make the alcohol content reach 70%, and refrigerated for 24 hours, filtered, and the filtrate is recovered by ethanol and reduced pressure concentrated to the extract II with relative density of 1.15 at 50-60°C, for standby;

[0160] E, take the extract II obtained in step D, and dry it in a belt vacuum dryer under the conditions of vacuum degree -0.09 MPa -0.10 MPa and drying temperature 62 °C, crush it, add starch and microcrystalline cellulose in the formula amount (weight ratio 7:2), mix them, granulate, dry, sieve, polish them in a polishing machine, and remove the broken capsules, to obtain the heart-through extract fine powder.

[0161] Example 5 Preparation of heart-through oral liquid

[0162]

[0163] A, take 13 kinds of medicinal materials of Huangqi, Dangshen, Maidong, Heshouwu, Yinyangheuo, Gegen, Dangui, Danshen, Zaokesheng, Haisheng, Kunkun, Muli and Zhishi, cut Maidong, Yinyangheuo and Zhishi into segments, cut Heshouwu, Gegen and Muli into blocks, cut Huangqi, Dangui and Danshen into slices, and grind Zaokesheng into fine powder;

[0164] B, take Gegen and Danshen decoction pieces in the prescription amount, add 8 times the amount of 70% ethanol, reflux for 2 times, each for 1.5 h, filter, combine the filtrates, and obtain ethanol extract I, and reserve the residue for use;

[0165] C, combine 11 kinds of raw medicinal materials of Huangqi, Dangshen, Maidong, Heshouwu, Yinyangheuo, Dangui, Zaokesheng, Haisheng, Kunkun, Muli and Zhishi with the residue of Gegen and Danshen obtained in step B, add 9 times the amount of water, decoct for 2 times, each for 1.5 h, combine the decoction liquid, filter, and reduce the pressure to concentrate the filtrate to 1000 mL to obtain decoction concentrate I;

[0166] D, combine the decoction concentrate I obtained in step C and the ethanol extract I obtained in step B, add ethanol to make the alcohol content reach 60%, and store it in the refrigerator for 24 h, filter, recover the ethanol from the filtrate, and reduce the pressure to concentrate it to 870 mL, and store it in the refrigerator for use;

[0167] E, filter the liquid stored in the refrigerator in step D, add 210 g of monosaccharide syrup, adjust the pH value to 7.0 with 20% sodium hydroxide solution, add water to 1000 mL, mix well, filter, seal, sterilize, and obtain the product.

[0168] Example 6 Preparation of heart-through microcapsules

[0169]

[0170] A, take 13 kinds of medicinal materials of Huangqi, Gegen, Danshen, Dangshen, Maidong, Heshouwu, Yinyangheuo, Dangui, Zaokesheng, Haisheng, Kunkun, Muli and Zhishi, cut Maidong, Yinyangheuo and Zhishi into segments, cut Heshouwu, Gegen and Muli into blocks, cut Huangqi, Dangui and Danshen into slices, and grind Zaokesheng into fine powder;

[0171] B, the prescription amount of the root of kudzu vine, Danshen pieces, 7 times the amount of 70% ethanol reflux 2 times, each 1.5h, filter, combined filtrate, get alcohol extract I for use, residue for use;

[0172] C, the prescription amount of the root of kudzu vine, Danshen pieces, 7 times the amount of 70% ethanol reflux 2 times, each 1.5h, filter, combined filtrate, get alcohol extract I for use, residue for use;

[0173] D, take step B alcohol extract I and step C obtained extract I combined, add ethanol to contain alcohol amount of 65%, cold storage 24h, filter, filter recovery of ethanol and reduced pressure concentration to 50-60℃ when the relative density of 1.16 of extract II, for use;

[0174] E, take step D extract II, under the condition of vacuum degree-0.08MPa-0.10Mpa, drying temperature 59℃ belt vacuum drying, crushing, get heart pass extract fine powder, for use;

[0175] F, according to the prescription amount of step E heart pass extract fine powder, capsule material, antiadhesive and plasticizer, wherein the capsule material is octenyl succinate starch: beta-lactoglobulin = 5:3, antiadhesive is octadecanol: titanium dioxide = 3:1, plasticizer is propylene glycol, the capsule material, antiadhesive and plasticizer are added to purified water, heated and stirred under the condition of 57℃ to dissolve, configure into a mass fraction of 31.5% of the capsule material solution, cool to room temperature, under the state of stirring, add heart pass extract fine powder and 1.22% of sucrose fatty acid ester: soybean phospholipid = 7:2 complex emulsifier by weight ratio, homogenization emulsification, get emulsion, for use;

[0176] G, step F emulsion under the condition of inlet air temperature 158℃, spray pressure 0.395MPa, feed speed 20.5mL / min spray drying, collect microcapsules, cool, get.

[0177] Example 7 preparation of heart pass granules

[0178]

[0179] A, take the root of kudzu vine, Danshen, party, Ophiopogon, Rehmannia glutinosa, Epimedium, Angelica, Gleditsia sinensis, sea algae, kelp, oyster and 13 kinds of fruit medicine, among them, Ophiopogon, Epimedium, net selection, party, sea algae, kelp after cutting, Rehmannia glutinosa, root of kudzu vine, oyster after cutting, Huangqi, Angelica, Danshen after cutting, Gleditsia sinensis after cutting into fine powder, for use;

[0180] B. Weigh the prepared slices of Radix Paeoniae Alba and Radix Salviae Miltiorrhizae according to the prescription, add 6 times the amount of 60% ethanol, and reflux for 2 times, each for 2.5 hours. Filter and combine the filtrates to obtain alcohol extract I for later use, and reserve the residue for later use;

[0181] C. Combine the residue of Radix Paeoniae Alba and Radix Salviae Miltiorrhizae from step B with 11 kinds of raw medicinal materials of Radix Astragali, Radix Codonopsis, Radix Ophiopogonis, Radix Polygoni Multiflori, Herba Epimedii, Radix Angelicae Sinensis, Radix Sophorae Tonkinensis, Sargassum, Ostreae Testa, and Fructus Aurantii, add 6 times the amount of water, and decoct for 2 times, each for 2 hours. Combine the decocted liquid, and filter. Reduce the pressure to concentrate the filtrate to the extract I with a relative density of 1.16 at 50-60°C;

[0182] D. Combine the alcohol extract I from step B and the extract I from step C, add ethanol to make the alcohol content reach 70%, and store in a refrigerator for 36 hours. Filter, recover the ethanol from the filtrate, and reduce the pressure to concentrate the filtrate to the extract II with a relative density of 1.13 at 50-60°C. Reserve the extract II for later use;

[0183] E. Take the extract II from step D, and dry it in a belt vacuum dryer under the conditions of a vacuum degree of -0.08 MPa to -0.10 MPa and a drying temperature of 60°C. Crush the dried extract II to obtain the fine powder of Xintong extract. Add the formula amount of the mixture of sucrose, hydroxypropyl starch, and mannitol (5:3:1) as auxiliary materials, mix well, make granules, dry, and size the granules to obtain the Xintong oral liquid.

[0184] Preparation of Xintong oral liquid

[0185]

[0186] A. Take 13 kinds of medicinal materials of Radix Astragali, Radix Paeoniae Alba, Radix Salviae Miltiorrhizae, Radix Codonopsis, Radix Ophiopogonis, Radix Polygoni Multiflori, Herba Epimedii, Radix Angelicae Sinensis, Radix Sophorae Tonkinensis, Sargassum, Ostreae Testa, and Fructus Aurantii. Cut Radix Ophiopogonis, Herba Epimedii, and Fructus Aurantii into segments after cleaning. Cut Radix Polygoni Multiflori, Radix Paeoniae Alba, and Ostreae Testa into blocks after cleaning. Cut Radix Astragali, Radix Angelicae Sinensis, and Radix Salviae Miltiorrhizae into slices after cleaning. Crush Radix Sophorae Tonkinensis into fine powder after cleaning. Reserve all the materials for later use;

[0187] B. Weigh the prepared slices of Radix Paeoniae Alba and Radix Salviae Miltiorrhizae according to the prescription, add 6 times the amount of 60% ethanol, and reflux for 2 times, each for 2.5 hours. Filter and combine the filtrates to obtain alcohol extract I for later use, and reserve the residue for later use;

[0188] C. Combine the residue of Radix Paeoniae Alba and Radix Salviae Miltiorrhizae from step B with 11 kinds of raw medicinal materials of Radix Astragali, Radix Codonopsis, Radix Ophiopogonis, Radix Polygoni Multiflori, Herba Epimedii, Radix Angelicae Sinensis, Radix Sophorae Tonkinensis, Sargassum, Ostreae Testa, and Fructus Aurantii, add 6 times the amount of water, and decoct for 2 times, each for 2 hours. Combine the decocted liquid, and filter. Reduce the pressure to concentrate the filtrate to the extract I with a relative density of 1.16 at 50-60°C;

[0189] D, Take the alcohol extract I of step B and the extract I of step C, add ethanol to make the alcohol content 65%, cold storage 48h, filter, recover the ethanol of the filtrate and concentrate under reduced pressure to the extract II with relative density 1.12 at 50-60℃, ready for use;

[0190] E, Take the extract II of step D, add 5 times the amount of purified water and stir to get the water extract, filter the water extract, add 1g activated carbon per 100mL filtrate, heat to 80℃ for 60min, filter to remove the carbon, add purified water to the total amount, adjust the pH to 7.3, add 0.55g β-cyclodextrin per 100mL liquid, control the inclusion temperature at 40℃, inclusion for 60min, filter, add purified water to the total amount, filter to the required clarity, fill, sterilize and package.

[0191] Example 9 Preparation of Xintong microcapsules

[0192]

[0193] A, Take 13 kinds of medicinal materials of Huangqi, Gegen, Danshen, Dangshen, Maidong, Huhu, Yinyanghuo, Dangui, Zaocongshi, Haizao, Kelp, Muli and Zhishi, cut Maidong, Yinyanghuo, Zhishi into segments, cut Huhu, Gegen, Muli into blocks, cut Huangqi, Dangui, Danshen into slices, and grind Zaocongshi into fine powder, ready for use;

[0194] B, Take Gegen and Danshen decoction pieces according to the prescription amount, add 7 times the amount of 70% ethanol and reflux for 2 times, 1.5h each time, filter, combine the filtrate to get alcohol extract I, and reserve the residue;

[0195] C, Take 11 kinds of raw medicinal materials of Huangqi, Dangshen, Maidong, Huhu, Yinyanghuo, Dangui, Zaocongshi, Haizao, Kelp, Muli and Zhishi and the residue of Gegen and Danshen of step B, add 9 times the amount of water and decoct for 2 times, 2h each time, combine the decocting liquid, filter, and concentrate the filtrate under reduced pressure to the extract I with relative density 1.18 at 50-60℃;

[0196] D, Take the alcohol extract I of step B and the extract I of step C, add ethanol to make the alcohol content 70%, cold storage 24h, filter, recover the ethanol of the filtrate and concentrate under reduced pressure to the extract II with relative density 1.17 at 50-60℃, ready for use;

[0197] E, Take the extract II of step D, make granules, and dry in a belt vacuum dryer under the conditions of vacuum degree-0.09MPa--0.10Mpa and drying temperature 61℃, crush to get Xintong extract fine powder, ready for use;

[0198] F. Weigh out the Xintong extract powder, capsule material, anti-sticking agent and plasticizer according to the prescription amount, wherein the capsule material is soybean protein isolate: maltodextrin: xanthan gum = 7:3:0.5, the anti-sticking agent is glycerol monostearate, and the plasticizer is polyethylene glycol: citric acid = 3:1. Add the capsule material, anti-sticking agent and plasticizer into purified water, heat and stir to dissolve at 58°C, and prepare a 30% capsule material solution. Cool to room temperature, and add the Xintong extract powder and 1.22% of a complex emulsifier of sucrose fatty acid ester: soybean phospholipid = 7:2 by weight under stirring, homogenize and emulsify to obtain an emulsion, which is ready for use;

[0199] G. Spray dry the emulsion of step F at an inlet air temperature of 157°C, a spray pressure of 0.399 MPa and a feeding speed of 21 mL / min, collect the microcapsules, and cool to obtain the product.

[0200] Preparation of Xintong Capsules

[0201]

[0202]

[0203] A. Take 13 kinds of medicinal materials of Huangqi, Gegen, Danshen, Dangshen, Maidong, Huhu, Yinyanghuo, Dangui, Zaokesheng, Haizao, Kelp, Muli and Zhishi, wherein Maidong, Yinyanghuo and Zhishi are selected as whole herbs, Dangshen, Haizao and Kelp are cut into segments after selection, Huhu, Gegen and Muli are cut into pieces after selection, Huangqi, Dangui and Danshen are sliced after selection, and Zaokesheng is crushed into fine powder after selection, and are ready for use;

[0204] B. Weigh out Gegen and Danshen decoction pieces according to the prescription amount, and reflux with 8 times the amount of 60% ethanol for 2 times, each for 2.5 h. Filter and combine the filtrates to obtain alcohol extract I, which is ready for use, and the residue is ready for use;

[0205] C. Weigh out 11 kinds of raw medicinal materials of Huangqi, Dangshen, Maidong, Huhu, Yinyanghuo, Dangui, Zaokesheng, Haizao, Kelp, Muli and Zhishi, and combine with the residue of Gegen and Danshen obtained in step B. Add 8 times the amount of water and decoct for 2 times, each for 1.5 h. Combine the decoction liquid, filter and reduce the pressure to concentrate the filtrate to an extract I with a relative density of 1.20 at 50-60°C;

[0206] D. Combine the alcohol extract I of step B and the extract I of step C, add ethanol to make the alcohol content reach 60%, and store in a refrigerator for 36 h. Filter, recover the ethanol from the filtrate, and reduce the pressure to concentrate the filtrate to an extract II with a relative density of 1.18 at 50-60°C, which is ready for use;

[0207] E, the extract II obtained in step D is vacuum dried under the conditions of vacuum degree -0.09 MPa to -0.10 MPa and drying temperature 62°C, pulverized, and then mixed with starch and microcrystalline cellulose (4:1 by weight) in the formula amount, granulated, dried, and whole-grained. The capsules are polished in a polishing machine, and the broken capsules are removed, thus obtaining the product.

Claims

1. The use of a Xintong preparation in the preparation of a drug for treating diabetes, wherein the Xintong preparation is made from the following components: Astragalus membranaceus 310-330 parts by weight, Codonopsis pilosula 160-180 parts by weight, Ophiopogon japonicus 110-130 parts by weight Polygonum multiflorum 90-110 parts by weight, Epimedium 90-110 parts by weight, Pueraria lobata 260-280 parts by weight Angelica sinensis 90-110 parts by weight, Salvia miltiorrhiza 180-200 parts by weight, Gleditsia sinensis thorns 90-110 parts by weight 160-180 parts by weight of seaweed, 160-180 parts by weight of kelp, and 160-180 parts by weight of oysters. 40-60 parts by weight of immature bitter orange.

2. The application according to claim 1, characterized in that, The diabetes mentioned is type II diabetes.

3. The application according to claim 1, characterized in that, The aforementioned diabetes syndrome in Traditional Chinese Medicine is classified as Qi and Yin deficiency type.

4. The application according to claim 1, characterized in that, The aforementioned cardiac preparation is made from the following components: Astragalus membranaceus 327 parts by weight, Codonopsis pilosula 176 parts by weight, Ophiopogon japonicus 126 parts by weight Polygonum multiflorum 101 parts by weight, Epimedium 101 parts by weight, Pueraria lobata 277 parts by weight Angelica sinensis 101 parts by weight, Salvia miltiorrhiza 189 parts by weight, Gleditsia sinensis thorns 101 parts by weight 176 parts by weight of seaweed, 176 parts by weight of kelp, and 176 parts by weight of oysters. 50 parts by weight of Citrus aurantium.

5. The application according to any one of claims 1-4, characterized in that, The aforementioned Xintong preparation is an oral medication.

6. The application according to claim 5, characterized in that, The oral drug preparation is one of granules, oral liquids, capsules, and microcapsules.

7. The application according to claim 6, characterized in that, The preparation process of the oral drug formulation includes the following steps: A. Take 13 raw medicinal materials: Astragalus membranaceus, Pueraria lobata, Salvia miltiorrhiza, Codonopsis pilosula, Ophiopogon japonicus, Polygonum multiflorum, Epimedium brevicornu, Angelica sinensis, Gleditsia sinensis thorns, Sargassum fusiforme, Laminaria japonica, Ostrea gigas, and Citrus aurantium. Among them, Ophiopogon japonicus, Epimedium brevicornu, and Citrus aurantium are cleaned and selected; Codonopsis pilosula, Sargassum fusiforme, and Laminaria japonica are cleaned and cut into sections; Polygonum multiflorum, Pueraria lobata, and Ostrea gigas are cleaned and cut into chunks; Astragalus membranaceus, Angelica sinensis, and Salvia miltiorrhiza are cleaned and sliced; Gleditsia sinen B. Weigh the kudzu root and salvia miltiorrhiza slices according to the prescription, add 6-9 times the amount of 60%-80% ethanol and reflux twice, each time for 1.5-2.5 hours, filter, combine the filtrates to obtain alcohol extract I for later use, and keep the residue for later use. C. Weigh out the following 11 raw medicinal materials according to the prescription: Astragalus membranaceus, Codonopsis pilosula, Ophiopogon japonicus, Polygonum multiflorum, Epimedium brevicornu, Angelica sinensis, Gleditsia sinensis thorns, Sargassum fusiforme, Laminaria japonica, Ostrea gigas, and Citrus aurantium. Combine them with the dregs of Pueraria lobata and Salvia miltiorrhiza obtained in step B. Add 6-9 times the amount of water and decoct twice, each time for 1.5-2.5 hours. Combine the decoctions, filter, and concentrate the filtrate under reduced pressure to extract I with a relative density of 1.16-1.22 at 50-60℃. Set aside for later use. D. Combine the alcohol extract I obtained in step B with the extract I obtained in step C, add ethanol to make the alcohol content reach 60%-70%, refrigerate for 24-48 h, filter, recover the ethanol from the filtrate and concentrate under reduced pressure to extract II with a relative density of 1.12-1.18 at 50-60℃, for later use. E. Take the extract II obtained in step D and prepare an oral pharmaceutical preparation by conventional processes or by adding pharmaceutically acceptable excipients.

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