TWI777606B - Traditional chinese medicine formula flora capsule, preparation method and use thereof in preparing medicine for treating type 2 diabetes - Google Patents

Abstract

The invention belongs to the field of medicines, and particularly relates to a traditional Chinese medicine formula flora capsule which is prepared by matching freeze-dried powder separated from fecal floral and traditional Chinese medicine extraction powder obtained by crushing traditional Chinese medicine extraction effective ingredients. The invention combines the traditional Chinese medicine extraction method and deeply integrates it with the fecal floral separation process to prepare the traditional Chinese medicine formula flora capsule, which greatly improves the treatment effect while changing the administration method, and realizes an efficient and comfortable treatment way.

Description

Traditional Chinese medicine formula bacteria capsule, preparation method and application in preparation of medicine for treating type 2 diabetes

The invention belongs to the technical field of medicine, in particular to the technical field of fecal bacteria transplantation, and more particularly to a traditional Chinese medicine formula fecal bacteria capsule, a preparation method thereof, and an application in the preparation of a medicine for treating type 2 diabetes.

Changes in the structure and function of intestinal flora can lead to a series of metabolic diseases such as obesity and type 2 diabetes. Recent studies have suggested that fecal microbiota transplantation can improve the level of blood sugar control in type 2 diabetes, improve metabolism, and improve insulin sensitivity.

"Fecal microbiota transplantation" (FMT), which is defined as the transplantation of functional flora in the stool of a healthy person into the gastrointestinal tract of a patient through nasogastric or duodenal tube, gastroscope or colonoscopy, rectal catheter enema, etc. , Rebuild the balance of intestinal flora, repair the barrier of intestinal mucosa, and realize the treatment of specific intestinal and extra-intestinal diseases.

However, although the above-mentioned administration method can achieve the purpose of intestinal bacteria transplantation, it needs to infuse the bacterial solution into the patient's intestine for treatment under the intubation state or under the endoscope, and the patient's physical and psychological acceptance is limited, which limits this The promotion and application of treatment technology in clinical practice. For example, Tian Hongliang et al. (Analysis of clinical efficacy of microflora capsules in the treatment of 15 cases of chronic transit constipation, Chinese Journal of Practical Surgery, Vol. The results of the study are preliminary It was not included in the control group, so how to overcome the shortcomings of fecal microbiota transplantation is still not enough. In particular, the content of the microflora capsule in this article is a single bacterial liquid, and the addition of conventional excipients will reduce the bacterial liquid content. Therefore, it is necessary to carry out further research and development to better apply fecal bacteria transplantation to the treatment of diseases.

In view of the above-mentioned problems, the present inventor extracted the traditional method of administration from fresh bacterial liquid and prepared it into freeze-dried powder, but the simple bacterial liquid freeze-dried powder sometimes needs to be matched with traditional Chinese medicine to improve the quality of treatment. In view of this The inventor combined the traditional Chinese medicine extraction method and deeply integrated the two processes to make the traditional Chinese medicine formula bacteria group capsule, which greatly improved the therapeutic effect while changing the administration method, and realized an efficient and comfortable treatment route.

The technical solutions provided by the present invention are as follows: On the one hand, the present invention provides a traditional Chinese medicine formula flora capsule, which is characterized in that it is prepared by cooperating with the freeze-dried powder after the separation of fecal bacteria and the traditional Chinese medicine extraction powder obtained by pulverizing the effective components of the traditional Chinese medicine extraction.

In a specific embodiment, the method for separating fecal bacteria is to separate the microorganisms in the contents of the cavity, and more specifically, to use the device described in the 201410606325.4 patent for separation.

More specifically, the preparation method of the lyophilized powder after the separation of the fecal bacteria comprises the following steps: (1) collecting fecal samples of healthy donors with a sterile sampling bottle, sealing and sending them to a sterile operating room, and mixing them with sterile disposable consumables. The filter bottle, AB bottle, deodorization bottle, buffer bottle, and bacterial liquid bottle are placed in series in the intelligent fecal bacteria separation system to collect bacteria; Soak the stool samples; (3) Turn on the air pump 2 to collect the mixed bacterial liquid in the sampling bottle into the buffer bottle through filters with different filter values in turn, and then perfuse the bacterial liquid in the buffer bottle into the bacterial liquid through the bacterial liquid driving device. bottle After centrifugation, the supernatant was removed after the centrifugation, and the precipitate was retained. This precipitate was the bacterial liquid precipitate after separation and purification; (4) Add glycerol to each centrifuge tube, mix with a shaker, pre-freeze it, and pre-freeze it. After the freezing is completed, the pre-frozen samples are quickly freeze-dried, and the freeze-dried bacterial liquid is dehydrated to obtain freeze-dried powder.

Further preferably, the sampling bottle is provided with a stirring rod, and in step (2), the stirring rod in the sampling bottle stirs the stool sample to make it fully homogenized.

In a preferred embodiment, the volume ratio of the bacterial flora freeze-dried powder and the traditional Chinese medicine extraction powder is 0.5-2:1, more preferably 1:1. Specifically, it is prepared by mixing the two with a micro-mixer, and then further filling with acid-resistant hypromellose capsules.

In a more preferred embodiment, the Chinese herbal extract powder is obtained by pulverizing the active ingredients extracted from the Chinese herbal formulas of American ginseng, Polygonatum chinensis, Divine Comedy, Digupi and Curcuma Radix. More preferably, the weight ratio of American ginseng, Polygonatum chinensis, Divine Comedy, Digupi and Curcuma in the Chinese medicine formula is 8-12:12-18:12-18:8-12:8-12, preferably 10: 15:15:10:10.

The extraction of the active ingredients of traditional Chinese medicine can be carried out by conventional methods. In a specific embodiment, the preparation method of the traditional Chinese medicine extraction powder is as follows: (1) chop or pulverize the medicinal materials in proportion, and place them in a decoction container; (2) add water (3) heating to boiling, leaching, separating the decocted liquid, decocting the dregs for 2-3 times according to the law, and collecting the decocted liquid; (4) carrying out alcohol extraction with the decoction liquid, preferably ethanol extraction; (5) ) The filtrate of alcohol extraction is dried and then pulverized with an ultrafine pulverizer, preferably an ultrafine powder less than 10 μm .

The present invention also provides the application of the traditional Chinese medicine formula microflora capsule in preparing a medicine for treating type 2 diabetes.

The present invention also provides the preparation method of the above-mentioned traditional Chinese medicine formula flora capsule, which comprises the steps of pulverizing and mixing the freeze-dried powder after separation of the fecal bacteria and the active ingredients extracted from the traditional Chinese medicine, wherein after mixing the two, a micro-mixer stirs and mixes to obtain a , and further filled with acid-resistant hypromellose capsules.

The present invention further provides a traditional Chinese medicine composition of a medicine for treating type 2 diabetes, the composition comprises American ginseng, Polygonatum chinensis, Divine Comedy, Digupi, Curcuma, wherein the weight ratio of them is 8-12:12-18:12 -18:8-12:8-12, preferably 10:15:15:10:10.

For the treatment mechanism of the present invention, the inventors based on the clinical characteristics of diabetes, which belongs to the category of "diabetes" in traditional Chinese medicine. Traditional Chinese medicine believes that the main pathogenesis of diabetes is "Yin deficiency is the main factor, and dryness and heat are the standard". Chinese medicine believes that the origin of the "heat" of diabetes is divided into "dry heat", "damp heat" and "stasis heat". The main pathological factors of a variety of stubborn diseases over time. And qi can generate body fluid, nourish yin and moisten dryness while giving qi medicine, you can receive better yin nourishing effect. Aiming at the pathogenesis characteristics of diabetes based on yin deficiency and mixed with blood stasis and heat, a treatment method for nourishing qi and nourishing yin, clearing heat and activating blood is formulated. The extracted active ingredients of traditional Chinese medicine were crushed and combined with fecal bacteria freeze-dried powder to make capsules, and their curative effects on type 2 diabetes were explored. In the present invention, American ginseng is the monarch medicine, nourishing qi and promoting body fluid, nourishing yin, moistening dryness and clearing heat, and treating diabetes with yin deficiency. Huangjing, Digupi, and Curcuma are the official medicines. Among them, Polygonatum is calm, invigorating qi and nourishing yin, moisturizing the lungs and nourishing the kidney, and helping American ginseng to invigorate Qi and invigorating body fluid; Digupi clears heat and cools blood, and Curcuma radices qi and breaks blood stasis. The spleen, Digupi and Curcuma are used together to clear away heat and cool blood to remove blood stasis, and to treat the symptoms of heat stasis. The Divine Comedy is used as an assistant, strengthens the spleen and stomach, digests food and dissolves accumulation, dispels accumulated heat in the stomach and intestines, and promotes the smooth flow of Qi. This recipe is refined and powerful, one drug has multiple effects, the compatibility is strict, and it is suitable for the pathogenesis. At the same time, all the medicines in this recipe have been verified by modern pharmacology to regulate blood sugar, lower lipids or improve hemodynamics. Divine Comedy can also improve intestinal flora imbalance.

The present invention has the following beneficial effects: the present invention combines the traditional Chinese medicine extraction method, deeply integrates it with the fecal bacteria separation process, and prepares traditional Chinese medicine formula flora capsules. The treatment effect is greatly improved, and an efficient and comfortable treatment approach is realized. The traditional Chinese medicine formula of the present invention and the intestinal flora are prepared by combining the traditional Chinese medicine formula flora capsule. The clinical verification shows that the therapeutic effect is remarkable, and the combination of the two has complementary effects, which not only makes up for the decoction of traditional Chinese medicine, taking It also overcomes the inconvenient shortcomings of the colonoscopy, and overcomes the pain caused by colonoscopy to assist patients during bacterial infusion, and the treatment effect has also been significantly improved. It not only meets people's requirements for being applicable, safe and effective, but also realizes people's desire for environmental protection, humanity and convenience.

FIG. 1 is a schematic structural diagram of the intelligent fecal bacteria separation system adopted in the present invention (ie, FIG. 1 in the 201410606325.4 patent).

FIG. 2 is a schematic structural diagram of the sterile disposable consumable of the present invention.

Figure 3 is a schematic flow diagram of the extraction process of traditional Chinese medicine.

4 is a schematic structural diagram of a stainless steel filter screen in the intelligent fecal bacteria separation system of the present invention. Among them, A grade is 1.0mm, B grade 600μm, C grade 500μm, D grade 350μm, E grade 250μm, F grade 200μm, G grade 150μm, H grade 100μm, I grade 70μm, J grade 60μm, K grade 40μm.

5 is a schematic diagram of the process flow diagram of the traditional Chinese medicine formula flora of the present invention.

Figure 6 shows the effect of the traditional Chinese medicine formula bacteria group capsule preparation solution on the fasting blood glucose of type 2 diabetes model rats.

Figure 7 shows the effect of the traditional Chinese medicine formula bacteria group capsule preparation liquid on the serum insulin of type 2 diabetes model rats.

Figure 8 shows the comparison of FBG before and after treatment in the two groups.

Figure 9 shows the comparison of PBG before and after treatment in the two groups.

Figure 10 shows the comparison of HbA1c before and after treatment in the two groups.

The present invention will be further clarified by the detailed description of the specific embodiments below, but it is not intended to limit the present invention, but only for illustration.

Example 1: Extraction of flora

The present invention uses the intelligent fecal bacteria separation system to automatically separate and extract the disposable consumables components, wherein the intelligent fecal bacteria separation system is a device for separating microorganisms in the cavity contents, the patent number is: ZL 201410606325.4, or a fecal analysis preprocessor, Model: FMT-5A-50/FMT-6A-50. Disposable consumables include filter bottle 3, separator tank 4, sub-bottle 5, deodorization device 8, liquid absorption and deodorization buffer bottle 11, bacterial liquid pipeline 22, etc.

The main steps of the bacterial flora extraction method of the present invention are as follows: collect 200 g of fecal samples from healthy donors with a sterile raw material tank (sterile disposable consumables, the structure of which is shown in Figure 2 ), seal it and send it to a sterile operating room, cooperate with a filter bottle 3 , separator tank 4, sub-bottling 5, deodorization device 8, liquid absorption and deodorization buffer bottle 11 and bacteria liquid pipeline 22, etc. are placed together in the intelligent fecal bacteria separation system for bacteria collection.

Add 1000ml of physiological saline into the sampling bottle to soak the stool sample through the liquid addition driving device 7, and stir the stool sample through the stirring device to make it fully homogenized.

Turn on the air pump 2 31 and pass the mixed bacterial liquid in the sampling bottle through A, B, C, D, E, F, J, H, I, J, K (see Figure 4 for specific values) in sequence through the filter bottles 3 with different filter values Pooled into sub-bottle 5. Centrifuge at 5°C, remove the supernatant after centrifugation, and retain the precipitate, which is the bacterial liquid precipitate after separation and purification, and the total weight is about 100 g.

About 10 ml (12.6 g) of glycerol was added to each sub-bottle 5, mixed well with a shaker, and placed in a -80°C refrigerator to pre-freeze for one hour. Immediately after the pre-freezing is completed, the pre-frozen samples are transferred to a bacterial liquid preparation freeze-drying machine (for example, product name: freeze dryer, manufacturer: Ningbo Xinzhi Biotechnology Co., Ltd., model: scientz-18N) for freeze-drying, and the pressure is 0.006Pa, the time is not less than 10 hours, and the freeze-dried bacterial liquid is dehydrated to obtain the bacterial group freeze-dried powder.

Example 2: Chinese medicine extraction

The traditional Chinese medicine is extracted by the traditional concentrated extraction method (see Figure 3 for the process flow of Chinese medicine extraction). Bone skin, curcuma, properly chopped or crushed, and placed in a decoction container.

Add an appropriate amount of water to submerge the medicinal materials for a suitable time.

Heat to boiling, leaching for a certain period of time, separate the decoction liquid, decoct the medicinal residues 2-3 times according to the law, and collect the decoction liquid.

Evaporate the decoction liquid to a specific gravity of 1:1, add 2 times ethanol after cooling, mix well, leave it overnight to make it precipitate, filter the clear liquid the next day, wash the precipitate with a small amount of 60% ethanol, wash the liquid Combine it with the filtrate, recover ethanol under reduced pressure, and when concentrated to a concentration of 1 g/ml, place it in a cold place (or add a certain amount of water and mix it) and let it stand for a certain period of time to make the precipitation complete and filter.

The filtrate is dried with a vacuum dryer, and then pulverized with an ultrafine pulverizer after drying to obtain a 10 μm ultrafine powder.

Embodiment 3: prepare traditional Chinese medicine formula flora capsule

The process flow of traditional Chinese medicine formula flora is shown in Figure 5. The freeze-dried powder of the flora in Example 1 and the extracted traditional Chinese medicine powder in Example 2 are mixed in a volume ratio of 1:1 and mixed with a micro mixer. The traditional Chinese medicine formula flora is prepared and filled with acid-resistant hypromellose capsules. Each capsule contains 1.5 grams of traditional Chinese medicine powder and 1.5 grams of bacterial powder, and is then packed in a sealed bag and stored in a -20°C refrigerator.

Embodiment 4: Therapeutic effect of traditional Chinese medicine formula bacteria group capsules on type 2 diabetes model rats

Through experimental research, the effects of the traditional Chinese medicine formula bacteria capsules of the present invention on glucose and lipid metabolism and insulin resistance in type 2 diabetes model rats are discussed.

1 Experimental material

1.1 Experimental animals

Forty male SD rats of SPF grade, weighing 200±20 g, were 8 weeks old. 5 per cage were kept in separate cages. Humidity 40%-60%, room temperature 16-26℃. Common feed, free food and water, feeding before dark. The food intake and water intake of the rats were dynamically observed, and the body weight was weighed once a week. Change cage litter once a day.

1.2 Drugs and Reagents

The concentration of the traditional Chinese medicine formula bacteria capsules prepared in Example 3 is 2.1 g/ml when used, which is the maximum concentration medicinal liquid that can pass through the rat gastric gavage device.

Pioglitazone (Ruitong, 15mg/tablet, Jiangsu Hengrui Pharmaceutical Co., Ltd., approved by Chinese medicine: H20040631).

Streptozotocin (STZ) (product of American sigma company). Glucose determination kit (Shanghai Rongsheng Bio-Pharmaceutical Co., Ltd.), insulin ELISA kit (produced by R&G Company in the United Kingdom, subpackaged by Shanghai Yuanxiang Medical Equipment Co., Ltd.). Trisodium citrate, citric acid, pentobarbital sodium.

1.3 High-sugar and high-fat feed formula

Cholesterol, lard, sucrose, egg yolk powder, common feed.

1.4 Main instruments and equipment

Blood glucose meter and blood glucose test strip (Johnson & Johnson Medical Equipment Company), automatic immune turbidity analyzer. Desktop centrifuges, several syringes, test tubes, beakers and measuring cylinders, precision electronic balances, electronic scales, tin foil, etc.

2 Experimental methods

2.1 Model making

16.7mmol/L確定為2型糖尿病大鼠模型。 After 1 week of adaptive feeding, they were randomly divided into a normal control group (10 animals) and a modeling group (30 animals). Rats were injected intraperitoneally with streptozotocin (STZ, 30mg/kg), and the normal control group (group A) was injected with the same amount of citrate buffer, blood was collected 72 hours later, and measured with the SureStepPlus blood glucose meter of Johnson & Johnson blood glucose, blood sugar

16.7mmol/L was identified as type 2 diabetes rat model.

2.2 Animal grouping and administration

After the model was established, the model rats were randomly divided into model control group (group B), pioglitazone group (group C), and traditional Chinese medicine formula bacteria group (group D), 10 rats each. Another 10 normal control group (group A) were set up. Group C was given pioglitazone 2.5 g/kg·d by gavage, group D was given 12 g/kg·d of traditional Chinese medicine formula microflora capsules by gavage; groups A and B were given the same amount of normal saline by gavage. The administration volume was 10ml/kg body weight, once a day, administered at a fixed time, and administered continuously for 8 weeks.

During the experiment, food and water were not restricted, and insulin and other hypoglycemic drugs were not used.

2.3 Blood Specimen Collection

Rats were sacrificed before modeling and the next day after 8 weeks after oral administration. Fasting for 12 hours before sacrifice, body weight, body length and tail length were measured; orbital blood samples were collected to prepare biochemical indicators such as insulin and blood sugar.

2.4 Detection of biochemical and immune indicators

Blood sugar was detected with an automatic biochemical analyzer. All assay items were operated in strict accordance with the kit instructions.

2.5 Statistical processing

Observe and compare the changes of each observation index in each group at different time periods, and use SPSS for Windows 22.0 statistical software for hypothesis testing and correlation analysis. All measurement data are expressed as mean±standard deviation (±SD), t-test was used for comparison between two groups and before and after, and analysis of variance (Oneway-ANOVA) was used for comparison between multiple groups. P<0.05 means the difference is statistically significant.

Experimental results

1 Effects of traditional Chinese medicine formula bacteria group capsules on fasting blood sugar in model rats

After treatment, the fasting blood glucose of the traditional Chinese medicine formula bacteria group and the pioglitazone group were significantly different from those before treatment (p<0.01). Sexual differences (p<0.01). The results are shown in Table 1 and Figure 6.

±s)

Table 1: Influence of traditional Chinese medicine formula bacteria group capsule configuration liquid on fasting blood glucose of type 2 diabetes model rats (

±s)

2 The effect of traditional Chinese medicine formula bacteria group capsules on serum fasting insulin in model rats

After treatment, the serum fasting insulin levels of the Chinese medicine formula bacteria group and pioglitazone group were significantly increased compared with those before treatment, with statistical significance (P<0.01). Sex difference (P<0.01). The results are shown in Table 2 and Figure 7.

Analysis of experimental results: Animal experiments showed that the fasting blood glucose of the traditional Chinese medicine formula group after treatment was significantly different from that before treatment (p<0.01), and there was also a significant difference compared with the model group (p<0.01). It is suggested that the traditional Chinese medicine formula microflora capsule has the effect of lowering blood sugar.

Compared with before treatment, the fasting serum insulin level of the rats in the traditional Chinese medicine formula bacteria group increased, which was statistically significant (P<0.01), and there was also a significant difference compared with the model group (P<0.01). prompt The medicinal formula microflora capsule has the effect of promoting insulin secretion and increasing the level of fasting insulin, which may achieve the result of lowering blood sugar through this effect.

Embodiment 5: Clinical observation of the clinical efficacy of traditional Chinese medicine formula bacteria capsules on type 2 diabetes mellitus

In order to verify the effect of the traditional Chinese medicine formula bacteria group capsule of the present invention in treating type 2 diabetes, we selected 60 patients to carry out the traditional Chinese medicine formula bacteria group capsule (the traditional Chinese medicine formula bacteria group capsule prepared in Example 3) (the clinical treatment of type 2 diabetes mellitus). All patients were randomly divided into two groups, including 30 cases in the treatment group and 30 cases in the control group. Before treatment, there was no significant difference in gender, age, course of disease, body mass index, etc. between the two groups of patients, and they were comparable. sex.

1. Treatment plan

Both groups received routine basic treatment, including health education, diet control, and regular exercise.

Control group: basic treatment + conventional western medicine (according to "Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2010 Edition)").

Treatment group: basic treatment + conventional western medicine (according to "China's Guidelines for the Prevention and Treatment of Type 2 Diabetes (2010 Edition)") + traditional Chinese medicine formula microflora capsules, 20 capsules each time, 2 times a day.

The two groups were treated for 4 weeks as a course of treatment, and three courses of treatment were observed.

2. Western medicine diagnostic criteria:

(1) Diabetes mellitus [according to the 1999 World Health Organization (WHO) diagnostic criteria for diabetes].

有明顯DM“三多一少”等症狀，隨機血糖

11.1mmol/L(200mg/dl)；

空腹靜脉血漿糖

7.0mmol/L(126mg/dl)；

OGTT(口服75g葡萄糖)2小時PG

11.1mmol/L(200mg/dl)

There are obvious DM symptoms such as "three more and one less", random blood sugar

11.1mmol/L (200mg/dl);

fasting venous plasma glucose

7.0mmol/L (126mg/dl);

OGTT (oral 75g glucose) 2 hours PG

11.1mmol/L(200mg/dl)

The above three items, if they meet one of them individually, can be used as the diagnostic basis and standard, but the diagnosis can be established if the results of the reexamination after a period of time still meet the diagnostic criteria.

(2) Diagnostic criteria for type 2 diabetes

With reference to the diabetes etiology classification criteria published in the journal Diabetes Care in July 1997, those who meet the diagnostic criteria for diabetes and the insulin release test results that meet one of the following conditions are diagnosed as type 2 diabetes.

以胰島素抵抗為主伴相對胰島素不足。

Insulin resistance is predominant with relative insulin insufficiency.

胰島素明顯缺乏伴胰島素抵抗。

Insulin deficiency is marked with insulin resistance.

3. Inclusion criteria

(1) Aged between 18 and 65 years old; (2) Informed consent; (3) Meet the diagnostic criteria for type 2 diabetes; (4) Any gender.

4. Exclusion criteria

(1) Elevated blood sugar caused by factors such as T1DM, pregnancy, drugs, etc.; (2) Those who fail to take medicines as prescribed, unable to judge the efficacy or incomplete data, etc., which affect the judgment of efficacy; (3) Patients who are participating in clinical studies of other drugs.

5. Changes of blood glucose and glycosylated hemoglobin in the two groups before and after treatment

There was no significant difference in blood glucose and glycosylated hemoglobin between the two groups before treatment (P>0.05), which was comparable. After treatment, the fasting blood sugar and postprandial blood sugar in the treatment group and the control group were significantly decreased, and there were significant differences compared with those before treatment (P<0.01). ), the improvement of postprandial blood glucose in the treatment group was different from that in the control group (P<0.05), and the improvement of glycosylated hemoglobin in the treatment group was different from that in the control group (P<0.05). See Table 3, Figure 8, Figure 9, Figure 10.

Table 3: Comparison of FBG, PBG, HbA1c between the two groups before and after treatment

6. Result analysis

After treatment, fasting blood sugar, postprandial blood sugar, and glycosylated hemoglobin in the treatment group and the control group were significantly decreased, and there was a difference compared with the control group (P<0.05 or P<0.01), indicating that conventional western medicine + traditional Chinese medicine formula bacteria group capsules can significantly reduce blood sugar in type 2 diabetes. The improvement effect is better than that of using conventional western medicine alone to control blood sugar.

Example 6: Clinical case

Typical cases in the clinical efficacy observation according to Example 5 are provided as follows. That is, the treatment plan of the case is: take 20 capsules each time, 2 times a day; every 4 weeks is a course of treatment; three courses of treatment are treated.

Case 1:

The patient Zhang, male, 72 years old, has a history of "type 2 diabetes" for more than 30 years. He has taken oral "gliclazide 30mgqd, acarbose 50mg tid" to control blood sugar, but the blood sugar control is not good, and then "saxagliptin" is added. 5mg qd", fasting blood sugar is controlled at 8.5-9.5mmol/l, postprandial blood sugar is 10-12mmol/l, and glycosylated hemoglobin is 7-7.5%. Obvious dry mouth and polydipsia, fat, dry stool, easy fatigue, bitter mouth, red tongue and yellow coating, thin pulse. Taking the traditional Chinese medicine formula microflora capsule of the present invention for three courses of treatment, the dry mouth and bitter taste, fatigue and fatigue are obviously improved, and the stool is once a day. The fasting blood sugar is controlled at about 7mmol/l, the postprandial blood sugar is about 8mmol/l, and the glycated hemoglobin is 6.8%.

Case 2:

The patient Wang Moumou, female, 69 years old, has a history of "type 2 diabetes" for 18 years. She used to take "metformin 500mg tid" orally to control blood sugar. Later, due to obvious gastrointestinal symptoms, she switched to "saxagliptin 5mg qd, repaglinide" 1mg tid", fasting blood sugar is controlled at 9-10mmol/l, postprandial blood sugar is 9-12mmol/l, glycosylated hemoglobin is about 8.5%, blood sugar fluctuates greatly, hypoglycemia reaction has occurred, and then dare not control diet excessively. Excessive food and easy hunger, abdominal distension, loose stools, easy to loose stools, easy fatigue, dry mouth, red tongue with little coating, thin pulse. Taking the traditional Chinese medicine formula microflora capsule of the present invention for three courses of treatment, the hunger is obviously relieved, the abdominal distension and the stool condition are obviously improved, the fasting blood sugar is controlled at 6-9 mmol/l, the postprandial blood sugar is about 10 mmol/l, and the glycosylated hemoglobin is 7.8%.

Case 3:

The patient Lu, male, 56 years old, has a history of "type 2 diabetes" for 10 years. He takes "metformin and saxagliptin" to control blood sugar, fasting blood sugar is controlled at 8-10mmol/l, postprandial blood sugar is 9-11mmol/l, glycation Hemoglobin 7.7%, dry mouth and polydipsia, easy abdominal distension and loose stools. Taking the traditional Chinese medicine formula microflora capsules of the present invention for three courses of treatment, the dry mouth, abdominal distension, and stool conditions were significantly improved, and metformin was stopped, the fasting blood sugar was controlled at 6-7mmol/l, the postprandial blood sugar was about 9mmol/l, and the glycosylated hemoglobin was 7.1. %.

Case 4:

The patient Jin Moumou, male, 81 years old, has a history of "type 2 diabetes" for more than 30 years. He has taken a variety of oral hypoglycemic drugs to control blood sugar, but the control is not good. Sitagliptin 100mg qd" controls blood sugar, fasting blood sugar is controlled at 7-10mmol/l, postprandial blood sugar is 8-14mmol/l, glycosylated hemoglobin is about 7.5%, blood sugar fluctuates greatly, diet control is poor, easy to be anxious, less exercise, abdominal distension , stool 2-3 days a line, red tongue, yellow coating, pulse string. Taking the traditional Chinese medicine formula microflora capsule of the present invention for three courses of treatment, the symptoms are obviously improved, the fasting blood sugar is controlled at 6-9 mmol/l, the postprandial blood sugar is about 9-10 mmol/l, and the glycosylated hemoglobin is 6.4%. The daily dose of insulin is reduced by 4u.

Case 5:

The patient Li Moumou, male, 43 years old, has a history of "type 2 diabetes" for 3 years. He took "metformin 1000 mg/day" to control blood sugar, his fasting blood sugar was good, his glycosylated hemoglobin was 6.5%, but his gastrointestinal symptoms were obvious. Abdominal distension, easy loose stool, pale red tongue with tooth marks, white and greasy fur. Because blood sugar control is relatively satisfactory, temporarily unwilling to replace hypoglycemic drugs, taking the traditional Chinese medicine formula microflora capsule of the present invention for three courses of treatment, abdominal distension and loose stools are improved, and metformin is stopped, and the glycosylated hemoglobin is 6.0%.

Case 6:

The patient Lin, male, 76 years old, has a history of "type 2 diabetes" for 20 years. He usually uses "subcutaneous insulin glargine injection 18u/day" + "acarbose oral 150mg/day" to control blood sugar, and fasting blood sugar is controlled at 6- 8 mmol/l, postprandial blood glucose 8-12 mmol/l, 2 hours after breakfast, blood glucose is about 11 mmol/l, the rest of the time blood glucose control is acceptable, glycated hemoglobin is 7.2%, dry mouth and polydipsia, loose stools, sticky toilet, red tongue Dry quality with little moss, thin and stringy pulse. Taking the traditional Chinese medicine formula microflora capsules of the present invention for three courses of treatment, the dry mouth and stool are obviously improved, the body is relaxed, the blood sugar after breakfast is 7-10 mmol/l, and the glycosylated hemoglobin is 7%.

Case 7:

The patient Li, male, 51 years old, was diagnosed with "type 2 diabetes" for 1 month. During the physical examination, it was found that the blood sugar was elevated, and the fasting amount was 12mmol/l. The thirst was obvious. At that time, "Novo Rui 30 early 22u evening 10u subcutaneous injection" was given in combination with "saxagliptin 5mg/day" to control blood sugar, and cooperated with the traditional Chinese medicine formula flora capsule of the present invention for three courses of treatment, and blood sugar control was better, After three courses of treatment, the thirst was significantly improved, and the glycated hemoglobin was 6.4%.

Case 8:

Patient Zhang, female, 70 years old, diagnosed with "type 2 diabetes" for 8 years, usually uses "Repaglinide 1mg tid" + "saxagliptin 5mg qd" to control blood sugar, fasting blood sugar is controlled at 7-8mmol/l, Postprandial blood glucose is 8-11mmol/l, glycosylated hemoglobin is 7.3%, dry mouth and polydipsia, loose stools, red tongue with little coating, and thin pulse. Combined with taking the traditional Chinese medicine formula microflora capsule of the present invention for three courses of treatment, the dry mouth and stool are obviously improved, the fasting blood sugar is 6-8 mmol/l, the postprandial blood sugar is 7-9 mmol/l, and the glycosylated hemoglobin is 6.4%.

Case 9:

The patient Lu Moumou, female, 81 years old, has been diagnosed with "type 2 diabetes" for nearly 40 years. He usually uses "Novo Rui 30 in the morning, 26 in the evening and 14 in the evening" to control blood sugar. Good, fluctuating, between 7-16mmol/l, difficult to control diet, glycosylated hemoglobin 8.4%, co-morbidities of "diabetic retinopathy and peripheral neuropathy", dry mouth and polydipsia, easy abdominal distension, numbness of hands and feet, poor vision Clear, itchy skin, memory loss, easy mouth ulcers, constipation, red tongue, thin yellow coating, stringy pulse. Instruct insulin to use in a standardized way, adjust the injection dose when eating more or when blood sugar is high, and take the traditional Chinese medicine formula flora capsule of the present invention for three courses of treatment. Difficult to change, blood sugar 7-11mmol/l, glycated hemoglobin 7%.

Case 10:

The patient Nan, male, 50 years old, has been diagnosed with "type 2 diabetes" for 12 years. He usually uses "insulin glargine 20u/day subcutaneous injection" + "Nuohelong 1 mg orally before three meals" to control blood sugar, and has "indigestion". Abdominal distension, the possibility of "gastroparesis" was considered 2 years ago, blood sugar fluctuated between 6-13mmol/l, eating a lot of undigested food, then abdominal distension, even vomiting, irregular stool, every 1-4 days, dry from time to time When thin, the tongue is reddish with tooth marks, the coating is white and greasy, and the pulse is weak. Instructing regular diet, and cooperating with taking the traditional Chinese medicine formula flora capsule of the present invention, for three courses of treatment, abdominal distension is obviously improved, no vomiting, stool is obviously improved, blood sugar is 6-11mmol/l, and glycosylated hemoglobin is 7.5%.

Case 11:

Patient Chen Moumou, female, 67 years old, has been diagnosed with "type 2 diabetes" for nearly 20 years. She has been treated with oral hypoglycemic drugs, but due to poor blood sugar control, she is now using "insulin glargine 14u/day subcutaneous injection" + "Aka" 50mg of Botang before three meals to control blood sugar, due to daily insulin injection, anxiety, fasting blood sugar about 7mmol/l, postprandial blood sugar 9-10mmol/l, glycated hemoglobin 8%, in conjunction with taking the traditional Chinese medicine formula flora of the present invention Capsules, after three courses of treatment, anxiety improved, insulin glargine dosage was reduced to 10u/day, fasting blood sugar was about 7mmol/l, postprandial blood sugar was 7-9mmol/l, and glycosylated hemoglobin was 7.5%.

Case 12:

The patient Zhang Moumou, male, 37 years old, was found to have elevated blood sugar on physical examination, and was later diagnosed with "type 2 diabetes". When found, fasting blood sugar was 7.2 mmol/l, postprandial blood sugar was 10.0 mmol/l, and glycosylated hemoglobin was 7.8%. , dry mouth, guide diet control, exercise in moderation, take traditional Chinese medicine formula flora capsules of the present invention, treat three courses of treatment, eat more and cause hunger, improve dry mouth, fasting blood sugar is about 6.5mmol/l, and postprandial blood sugar is about 8.0mmol/l , Glycated hemoglobin 7.3%.

Claims (10)

The traditional Chinese medicine formula microflora capsule is prepared by cooperating with the freeze-dried powder after the separation of fecal bacteria and the extraction of the active ingredients of traditional Chinese medicine to obtain the traditional Chinese medicine extraction powder; wherein the preparation method of the freeze-dried powder after the separation of the fecal bacteria comprises the following steps: (1) Use sterile sampling bottles to collect fecal samples from healthy donors, seal them to the sterile operating room, and place them in series with the filter bottles, AB bottles, deodorizing bottles, buffer bottles and bacterial liquid bottles in sterile disposable consumables. Bacteria collection in the separation system; (2) Filling the normal saline into the sampling bottle to soak the fecal samples through the automatic liquid filling device through the liquid addition drive device; (3) Turning on the air pump to turn on the mixed bacterial liquid in the sampling bottle in turn Collected into the buffer bottle through filters with different filtration values, and then perfused the bacterial liquid in the buffer bottle into the bacterial liquid bottle through the bacterial liquid driving device, and then centrifuged. After centrifugation, the supernatant was removed and the precipitate was retained. The bacterial liquid precipitate after separation and purification; (4) Add glycerol to each centrifuge tube, mix with a shaker, and pre-freeze it. The lyophilized powder is obtained after the bacterial liquid is dehydrated; the traditional Chinese medicine extraction powder is obtained by pulverizing the active ingredients extracted from the traditional Chinese medicine formula composed of American ginseng, Polygonatum chinensis, Divine Comedy, Digupi and Curcuma Radix. The traditional Chinese medicine formula flora capsule according to claim 1, wherein the sampling bottle is provided with a stirring rod, and in step (2), the stirring rod in the sampling bottle stirs the stool sample to make it fully homogenized. The traditional Chinese medicine formula flora capsule according to claim 1 or 2, wherein the volume ratio of the freeze-dried powder separated from the fecal bacteria and the Chinese medicine extraction powder is 0.5-2:1;

The freeze-dried powder and the traditional Chinese medicine extraction powder are mixed uniformly by mixing the two and then agitating and mixing by a micro-mixer. The traditional Chinese medicine formula flora capsule according to claim 3, wherein the volume ratio of the freeze-dried powder separated from the fecal bacteria and the described traditional Chinese medicine extraction powder is 1:1. The traditional Chinese medicine formula flora capsule according to claim 3 is further filled with acid-resistant hypromellose capsules to obtain the traditional Chinese medicine formula flora capsule. The traditional Chinese medicine formula flora capsule according to claim 4, wherein: further fill with acid-resistant hypromellose capsules to obtain the traditional Chinese medicine formula flora capsule. The traditional Chinese medicine formula microflora capsule according to claim 1, wherein the weight ratio of American ginseng, Polygonatum chinensis, Divine Comedy, Digupi and Curcumae in the traditional Chinese medicine formula is 8-12:12-18:12-18:8-12: 8-12. The traditional Chinese medicine formula microflora capsule according to claim 7, wherein the weight ratio of American ginseng, Polygonatum chinensis, Divine Comedy, Digupi and Curcumae in the traditional Chinese medicine formula is 10:15:15:10:10. The traditional Chinese medicine formula flora capsule according to claim 7 or 8, wherein the preparation method of the traditional Chinese medicine extraction powder is as follows: (1) chop or pulverize the medicinal materials in proportion, and place them in a decoction container; (2) add water to soak; (3) ) heating to boiling, leaching, separating the decocting liquid, the medicinal residues are decocted 2-3 times according to the law, and the decocting liquid is collected; (4) the decocting liquid is carried out ethanol extraction; (5) the filtrate of the ethanol extraction is dried and used again The ultrafine pulverizer pulverizes it into ultrafine powder below 10 μm . An application of the traditional Chinese medicine formula microflora capsule as described in any one of claims 1 to 9 in the preparation of a medicine for treating type 2 diabetes.

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