JP2022001572A - Chinese medicine prescription flora capsule, manufacturing method thereof, and use of chinese medicine prescription flora capsule in manufacture of therapeutic agents for type 2 diabetes - Google Patents

Abstract

To change an administration method and greatly improve a therapeutic effect so as to realize an efficient and comfortable treatment approach, by manufacturing Chinese medicine prescription flora capsules by deeply combining a Chinese medicine extraction method and a fecal flora separation process.SOLUTION: The present invention belongs to a pharmaceutical field and specifically provided is a Chinese medicine prescription flora capsule obtained by mixing a freeze-dried powder of a flora separated from feces and a Chinese medicine extract powder obtained by extracting an active ingredient from a Chinese medicine and crushing the active ingredient.SELECTED DRAWING: Figure 5

Description

The present invention belongs to the field of pharmaceutical technology, specifically relating to the technical field of fecal flora transplantation, more specifically, a Kampo prescription fecal flora capsule, a method for producing the same, and a Kampo fecal bacterium in a therapeutic agent for type 2 diabetes. Regarding the use of flora capsules.

Changes in the structure and function of the intestinal flora can cause a series of metabolic disorders such as obesity and type 2 diabetes. Recent studies have shown that fecal flora transplantation therapy can improve glycemic control levels, metabolism and insulin sensitivity in patients with type 2 diabetes.

"Fecal microbiota transplantation" (Fecal microbiota transplantation, FMT) is a functional flora contained in the stool of a healthy person. It means to realize treatment for specific intestinal and extraintestinal diseases by transplanting into the gastrointestinal tract of a patient by a method such as enema, balancing the intestinal flora, and repairing the barrier of the intestinal mucosa. ..

However, although the above-mentioned administration method can achieve the therapeutic purpose of intestinal flora transplantation, it is necessary for the patient to inject the bacterial solution into the intubation of the patient in an intubated state or using an endoscope for treatment. The psychologically and physiologically unacceptable nature limits the widespread use of clinical applications of this therapeutic technique. Hiroaki Ta et al. Used the flora capsule in "Clinical effect analysis of 15 cases of treatment of constipation with extended colon transit time using the flora capsule" (Chinese Practical Surgery Magazine, April 36, 4th phase). We report an analysis of the clinical efficacy of 15 patients treating prolonged constipation. However, this study is an attempt only, does not use a control group, and does not adequately overcome the shortcomings of fecal flora transplantation. In particular, in this document, the content of the bacterial flora capsule is a single bacterial fluid, and the addition of common auxiliary materials reduces the bacterial fluid content, making fecal flora transplantation better for the treatment of disease. Further research is needed to apply to.

In response to the above problems, the present inventor extracted the conventionally administered pharmaceutical components with a fresh bacterial solution to prepare a freeze-dried powder. However, in order to improve the treatment quality, it is necessary to use the freeze-dried powder of bacterial solution in combination with Chinese herbal medicine. In view of this, the present inventor uses the Chinese medicine extraction method and combines the two processes to prepare a Chinese medicine prescription flora capsule, whereby the administration method is changed and the therapeutic effect is greatly improved. , An efficient and comfortable treatment approach is realized.

The technical means of the present invention are as follows.
According to the present invention, there is provided a Chinese medicine prescription fungus capsule obtained by mixing a freeze-dried powder of a bacterial flora separated from feces and a Chinese medicine extract powder obtained by extracting an active ingredient from a Chinese medicine and crushing the active ingredient.

In a specific embodiment, in the method for separating the bacterial flora from the feces, the microbial flora is separated by using a microbial separation device in the lumen contents, specifically, by the device described in Chinese Patent 2014106066325.4.

More specifically, the method for producing a freeze-dried powder of the flora isolated from the feces includes the following steps (1) to (4).
In step (1), a healthy donor's fecal sample is collected from a sterile sampling bottle, sealed and transferred to a sterile operation room, and is a sterile disposable consumables such as a filtration bottle, an AB bottle, a deodorizing bottle, a buffer bottle, and a bacterial solution bottle. Together with the intelligent fecal flora isolation system placed in series to collect the flora,
In step (2), physiological saline is added to the sampling bottle by the liquid addition drive device to immerse the stool sample.
In step (3), the air pump 2 is started so that the mixed bacterial solution in the sampling bottle passes through the filtration nets having different filtration values and collects in the buffer bottle, and the bacterial solution in the buffer bottle is further discharged by the bacterial solution drive device. After injecting into a bacterial solution bottle, the mixture is centrifuged, and after the centrifugation is completed, the supernatant is removed leaving a precipitate. The precipitate is a bacterial solution precipitate after separation and purification.
In step (4), glycerin is added to each centrifuge tube, mixed uniformly with a shaker, pre-frozen, the sample immediately after pre-freezing is lyophilized, and the lyophilized bacterial solution is dehydrated and lyophilized. Get the powder.

More preferably, the sampling bottle is provided with a stirring rod, and the stool sample is stirred by the stirring rod in the sampling bottle in step (2) so as to be sufficiently uniform.

In a preferred embodiment, the volume ratio of the freeze-dried powder of the flora to the extracted powder of Chinese herbal medicine is 0.5-2: 1, preferably 1: 1. Specifically, after mixing the two, the mixture is uniformly stirred with a micromixer and then filled in acid-resistant hypromerose capsules.

In a more preferred embodiment, the Chinese herbal medicine extract powder is obtained by extracting an active ingredient from a Chinese ginseng, yellow spirit, Jiuqu, gedoary bark, and zedoary Chinese herbal formula and pulverizing it. More preferably, the weight ratio of American ginseng, yellow spirit, Jiuqu, Jiuqu, and Polygonatum sibi in the Chinese herbal formula is 8-12: 12-18: 12-18: 8-12: 8-12. It is preferably 10:15:15:10:10.

Extraction of the active ingredient of Chinese herbal medicine can be performed by a usual method. In a specific embodiment, the method for producing the Chinese herbal medicine extract powder includes the following steps (1) to (5).
In step (1), take the crude drug at a predetermined ratio, chop or crush it, put it in a decoction container, and put it in a decoction container.
In step (2), add water and soak.
In step (3), the mixture is heated to a boil, exuded, the decoction is separated, the crude drug residue is decoction 2-3 times by the usual method, and the decoction is collected.
In step (4), the decoction is extracted with alcohol, preferably ethanol.
In step (5), the alcohol-extracted filtrate is dried and then pulverized by an ultrafine pulverizer to pulverize it into an ultrafine powder of preferably less than 10 μm.

INDUSTRIAL APPLICABILITY According to the present invention, the use of the Chinese herbal prescription flora capsule in the production of a therapeutic agent for type 2 diabetes is further provided.

According to the present invention, the present invention comprises a step of crushing and uniformly mixing the freeze-dried powder of the bacterial flora separated from the feces and the active ingredient extracted from Chinese herbal medicine, where the two are mixed and then uniformly stirred by a micromixer. Further provided is a method for producing the Chinese herbal formula capsule, which is further filled with an acid-resistant hypromerose capsule.

INDUSTRIAL APPLICABILITY According to the present invention, a Chinese herbal medicine composition for treating type 2 diabetes is further provided. The composition comprises ginseng, yellow spirit, Jiuqu, zedoary bark, and zedoary, and their weight ratio is 8-12: 12-18: 12-18: 8-12: 8-12, preferably 10:15. : 15:10:10.

The therapeutic mechanism of the present invention belongs to the "depletion" of traditional Chinese medicine, according to the clinical features of diabetes. In traditional Chinese medicine, the main illness of depletion is yin and yang fever, with yin as the book and dry fever as the target. In Chinese medicine, the "fever" of depletion is divided into "dry fever", "wet fever", and "diabetic fever". Among these three fever, diabetic symptoms often show strange symptoms, are difficult to treat, and depletion is the main cause of various stubborn illnesses. In addition, since Qi can generate tsu juice, it is possible to achieve a better Yin-Yang effect by administering a Qi-Yin drug at the same time as the moisturizing and dryness of Qi. Based on the pathological mechanism of diabetes, "the shadow is the book, and the fever is the mark", we adopted the treatment method of profitable yin and fresh heat active blood. The active ingredient was extracted from the above, and the extracted active ingredient of Polygonatum sibifolia was crushed, and then a capsule was produced by delicately combining it with the frozen and dried powder of the fecal flora, and the therapeutic effect on type 2 diabetes was examined. In the present invention, American ginseng is a princely medicine, which has the effects of Maki Ikutsu, Jiyin Jun, and Qing Fever, and treats the illness of diabetes. Yellow spirit, zedoary bark, and zedoary are vassals. Among them, Huangsei is flat and has the effect of assisting the supplemental Qi nourishment, the swelling lung benefit kidney, and the Western ginseng's benefit Ikutsu. The sarcophagus has the effect of clear heat and cool blood. Zedoary has the effects of debilitating and healthy spleen. The zedoary skin and the zedoary have the same action, and have the effect of clear heat and cool blood, and can treat the symptoms of zedoary. Jiuqu is a sacrifice and has the effects of healthy splenic Japanese stomach, antiseptic product, intestinal gastric fever elimination, and motility. The formulation of the present invention has a small number of crude drugs and is highly effective, exhibits a plurality of effects, is carefully formulated, and is suitable for the diseased machine. In addition, modern pharmacology has demonstrated that all of the drugs of this prescription have the effects of blood glucose regulation, lipid lowering, and hemodynamic improvement. Jiuqu can also improve gut microbiota. Therefore, the effect of the prescription of the present invention is strongly convincing because it is demonstrated by both traditional Chinese medicine and Western medicine.

The present invention has the following beneficial effects. In the present invention, by producing a Kampo prescription flora capsule by deeply combining the Kampo drug extraction method and the fecal flora separation process, the administration method is changed and the therapeutic effect is significantly improved, which is efficient. A comfortable treatment approach is realized. The Kampo prescription flora capsule produced by combining the Kampo prescription of the present invention and the intestinal flora has been proved to have a remarkable therapeutic effect by clinical verification, and the combination of both has a complementary effect and is a Chinese medicine. While solving the disadvantage that it is inconvenient to decoction and difficult to take, using a colonoscope at the time of injecting the flora overcomes the pain caused to the patient and significantly improves the therapeutic effect. .. The requirements for application, safety and effectiveness are met, while the requirements for environmental protection, humanity and convenience are fulfilled.

It is a structural schematic diagram of the intelligent fecal flora isolation system used in the present invention (that is, FIG. 1 of Chinese Patent 201414066325.4). It is a structural schematic diagram of the sterile disposable consumables of this invention. It is a flowchart of a Chinese medicine extraction process. It is a structural schematic diagram of the stainless steel filtration net in the intelligent fecal flora separation system of this invention. Here, A grade is 1.0 mm, B grade is 600 μm, C grade is 500 μm, D grade is 350 μm, E grade is 250 μm, F grade is 200 μm, G grade is 150 μm, H grade is 100 μm, and I grade is 70 μm. The J grade is 60 μm and the K grade is 40 μm. It is a flowchart of the process of the Chinese medicine prescription flora of this invention. The effect of the Chinese herbal prescription flora capsule preparation solution on the fasting blood glucose level of type 2 diabetes model rats is shown. The effect of the Chinese herbal prescription flora capsule preparation solution on serum insulin in type 2 diabetes model rats is shown. A comparison of FBG before and after treatment of the two groups is shown. A comparison of PBG before and after treatment of the two groups is shown. A comparison of HbA1c before and after treatment of the two groups is shown.

Hereinafter, the present invention will be described in more detail with reference to specific embodiments, but these embodiments do not limit the present invention and are merely exemplary.

Example 1: Extraction of bacterial flora In the present invention, an intelligent fecal flora separation system and disposable consumables are used to automatically separate and extract the bacterial flora. Here, the intelligent fecal flora separation system is a microbial separation device in luminal contents (Chinese patent ZL2014106066325.4) or a fecal analysis pretreatment device (model number: FMT-5A-50 / FMT-6A-50). Disposable consumables include a filtration bottle 3, a separation can 4, a dispensing bottle 5, a deodorizing device 8, a liquid absorbing deodorizing buffer bottle 11, a bacterial solution conduit 22, and the like.

The main steps of the bacterial flora extraction method of the present invention are as follows.
Using a sterile raw material tank (sterile disposable consumables, Fig. 2), 200 g of fecal samples of healthy donors are collected, sealed and transferred to a sterile operation room, where 3 filtration bottles, 4 separation cans, 5 dispensing bottles and deodorization are performed. The bacterial flora was collected by putting it in an intelligent fecal flora separation system together with the device 8, the liquid absorbing / deodorizing buffer bottle 11, the bacterial solution conduit 22, and the like.

The stool sample was immersed by injecting 1000 ml of physiological saline into the sampling bottle by the liquid addition driving device 7, and the stool sample was stirred by the stirring device so as to be sufficiently uniform.

Start the air pump 2 31 and filter the mixed bacterial solution in the sampling bottle in order of A, B, C, D, E, F, J, H, I, J, K (see FIG. 4 for specific values). It was passed through filtration bottles 3 having different values and collected in a dispensing bottle 5. Centrifugation was performed under the condition of 5 ° C., and then the supernatant was discarded to leave a precipitate. This precipitate was a bacterial solution precipitate after separation and purification, and the total weight was about 100 g.

About 10 ml (12.6 g) of glycerin was added to each dispensing bottle 5, mixed uniformly with a shaker, placed in a -80 ° C refrigerator, and pre-frozen for 1 hour. Immediately after the completion of pre-freezing, the sample after pre-freezing is transferred to a bacterial solution preparation freeze-dryer (for example, trade name: freeze-dryer; manufacturer: Ningbo New Lawn Science and Technology Co., Ltd .; model number: scientistz-18N) and pressure is applied. Freeze-dried at 0.006 Pa for 10 hours or more, and the lyophilized bacterial solution was dehydrated to obtain a lyophilized powder.

Example 2: Extraction of Chinese herbal medicine The active ingredient of Chinese herbal medicine is extracted by a conventional concentrated extraction method (see FIG. 3 for the Chinese herbal medicine extraction process), and the specific method is as follows.
At a weight ratio of 10:15:15:10:10, crude drugs such as American ginseng, yellow spirit, Jiuqu, zedoary bark, and zedoary were taken, shredded or crushed as appropriate, and placed in a decoction container.

An appropriate amount of water was added so that the crude drug was completely immersed, and the mixture was immersed for an appropriate time.

The mixture was heated to a boil, leached for a predetermined time, the decoction was separated, the crude drug residue was decoctioned 2-3 times by a conventional method, and the decoction was collected.

The water decoction is evaporated to a specific gravity of 1: 1 and cooled, then double ethanol is added, mixed uniformly, left overnight to precipitate, the next day the supernatant is filtered and a small amount of 60 precipitates. After washing with% ethanol, combining the washing liquid and the filtrate, recovering the ethanol under reduced pressure, transfer to a cooling place (or add a certain amount of water and mix uniformly) when concentrated to a concentration of 1 g / ml, and mix for a certain period of time. It was allowed to stand, completely precipitated and filtered.

The filtrate was dried in a vacuum dryer, dried, and then pulverized by an ultrafine pulverizer to obtain an ultrafine powder of 10 μm.

Example 3: Production of Kampo Prescription Bacterial Capsule The process of Kampo Prescription Bacterial Capsule is shown in FIG. The lyophilized powder of Example 1 and the extracted powder of Chinese herbal medicine of Example 2 were mixed at a volume ratio of 1: 1 and then uniformly stirred with a micromixer to produce a Chinese herbal formula and each capsule. The capsules were filled with acid-resistant hypromerose capsules so as to contain 1.5 g of Chinese herbal medicine powder and 1.5 g of fungal powder, and the capsules were further packaged in a sealed packaging bag and then stored in a refrigerator at −20 ° C.

Example 4: Therapeutic effect of the Chinese prescription bacterial flora capsule on the type 2 diabetes model rat The effect of the Chinese herbal prescription flora capsule of the present invention on the glycolipid metabolism and insulin resistance of the type 2 diabetes model rat was analyzed by experimental study.

1 Experimental material 1.1 Experimental animal SPF grade SD male rat (40), body weight: 200 ± 20 g, 8 weeks old. The animals were divided into 5 animals / cages and bred at a humidity of 40% -60% and a room temperature of 16-26 ° C. They were fed regular feed, had free water intake, and were fed before night. The food intake and water intake of the rats were dynamically observed, and the body weight was measured once a week. The cage mat was changed daily.

1.2 Drugs and Reagents The Kampo prescription flora capsules obtained in Example 3 were prepared at a concentration of 2.1 g / ml at the time of use. This concentration is the maximum concentration that can pass through the rat intragastric dispenser.

Pioglitazone (15 mg / tablet, Jiangsu Henglui Pharmaceutical Co., Ltd., national drug quasi-character: H20040631).

Streptozotocin (STZ) (a product of sigma, USA). Glucose measurement kit (Shanghai Sheng Biopharmaceutical Industry Co., Ltd.), Insulin ELISA kit (manufactured by UK R & G, Shanghai Medical Instrument Co., Ltd.). Trisodium citrate, citric acid, sodium pentobarbital.

1.3 Prescription of high-fat / high-carbohydrate feed Cholesterol, lard, sucrose, egg yolk powder, normal feed.

1.4 Main equipment and equipment Glucose meters and blood glucose test strips (Johnson & Johnson Medical Devices Companies), automatic immunoturbidity analyzer. Desktop centrifuges, multiple syringes, test tubes, beakers and multiple graduated cylinders, precision electronic balances, electronic scales, tin foil paper, etc.

2 Experimental method 2.1 Preparation of model After adaptive feeding for 1 week, the animals were randomly divided into a normal control group (10 animals) and a model group (30 animals), and the normal control group was given a normal feed, and the model group was given high fat. After feeding a high-sugar feed for 6 weeks, a single intraperitoneal injection of streptzotocin (STZ, 30 mg / kg) was given to the model group rats, and a single injection of an equal dose of citrate buffer was given to the normal control group (group A). , 72 hours later, blood is collected, and whole blood blood glucose is measured with Johnson &Johnson's SureStepPlus glucose meter, and if the blood glucose level is ≥16.7 mmol / L, it is confirmed to be a type 2 diabetic rat model.

2.2 Grouping and administration of animals After creating a model, 10 model rats were randomly divided into a model control group (group B), a pioglitazone group (group C), and a Chinese herbal prescription flora group (group D). divided. Separately, a normal control group (group A) of 10 animals was provided. Pioglitazone 2.5 g / kg · d was intragastrically administered to group C, and 12 g / kg · d of the preparation solution of Chinese herbal prescription bacterial flora capsule was intragastrically administered to group D, and equal amounts of physiological saline were administered to groups A and B. Water was administered intragastrically. The administration volume was 10 ml / kg body weight, and the drug was administered once / day for a fixed time and continuously for 8 weeks.

No restrictions were placed on food and water intake during the experimental period, and insulin and other hypoglycemic agents were not used.

2.3 Blood sample collection Rats were euthanized before model construction and 8 weeks after intragastric administration. Before euthanasia, the patient was fasted for 12 hours, the body weight, body length and tail length were measured, the orbital blood was collected, and biochemical indicators such as insulin and blood glucose were measured.

2.4 Detection of biochemical and immunological indicators Blood glucose was detected by an automatic biochemical analyzer. All measurement items were operated according to the instructions in the kit.

は分散分析（Ｏｎｅｗａｙ−ＡＮＯＶＡ）で行った。Ｐ＜０．０５は統計的有意差があることを示す。2.5 Statistical processing Hypothesis testing and correlation analysis were performed using SPSS for Windows 22.0 statistical software after observing and comparing the changes in each observation index in different time zones of each group. All measurement data are average

Was performed by analysis of variance (Oneway-ANOVA). P <0.05 indicates that there is a statistically significant difference.

Results of the experiment Effect of the Chinese prescription flora capsule preparation solution on the fasting blood glucose level of 1 model rat The fasting blood glucose levels of the Chinese prescription flora group and the pioglitazone group after the treatment are both remarkable as compared with those before the treatment. There is a significant difference (p <0.01), and the fasting blood glucose levels of the Chinese herbal prescription flora group and the pioglitazone group after treatment are both significantly different (p <0.01) compared to the model group. be. The results are shown in Table 1 and FIG.

Effect of Chinese Prescription Bacterial Capsule Preparation Solution on Serum Hungry Insulin in 2 Model Rats The rat serum hungry insulin levels in the Chinese prescription bacterial flora group and pioglitazone group after treatment were significantly higher than those before treatment and were statistically significant. There is sex (P <0.01), and both groups have a significant significant difference (P <0.01) compared to the type 2 diabetes model group. The results are shown in Table 2 and FIG.

Experimental results and analysis: According to animal experiments, the fasting blood glucose level after treatment of the Kampo prescription flora group was significantly different from that before treatment (p <0.01), which was remarkable compared to the model group. It is shown that there was a significant difference (p <0.01). This indicates that the Kampo prescription flora capsule has a blood glucose lowering effect.

Fasting serum insulin levels after treatment in rats in the Chinese prescription flora group were elevated compared to before treatment and were statistically significant (P <0.01), with a significant significant difference compared to the model group. There was (P <0.01). This indicates that the Kampo prescription flora capsule has an action of promoting insulin secretion and improving the level of hungry insulin, and this action may realize a hypoglycemic effect.

Example 5: Observation of clinical effect of Chinese prescription bacterial flora capsule on type 2 diabetes In order to verify the therapeutic effect of the Chinese herbal prescription bacterial flora capsule of the present invention on type 2 diabetes, the present inventor selected 60 patients. Then, type 2 diabetes was treated with the Kampo-prescribed flora capsule (Chinese-prescribed flora capsule produced in Example 3) and clinically observed. All patients were randomly divided into two groups, including 30 in the treatment group and 30 in the control group. Prior to treatment, patients in both groups had no statistically significant differences in gender, age, disease course, body mass index, etc. and could be compared.

1. Treatment plan General basic treatment including health education, eating and drinking control, and regular exercise was given to patients in both groups.

Control group: Basic treatment + treatment with general Western medicine (Chinese type 2 diabetes control guidance (2010 version)).

Treatment group: Basic treatment + treatment with general Western medicine (Chinese type 2 diabetes control guidance (2010 version)) + treatment with Chinese medicine prescription bacterial flora capsule (2 times / day, 20 tablets / time).

In both groups, 4 weeks was regarded as one treatment course, and 3 treatment courses were observed.

2. Diagnosis standard of Western medicine (1) Diabetes [according to the diabetes diagnosis standard established by WHO in 1999].
(1) DM "Mita Ichisho" and other symptoms are prominent, and random blood glucose level ≥ 11.1 mmol / L (200 mg / dl)
(2) Fasting venous plasma blood glucose level ≧ 7.0 mmol / L (126 mg / dl)
(3) OGTT (oral administration of 75 g glucose) 2 hours PG ≧ 11.1 mmol / L (200 mg / dl)
If one of the above three conditions is satisfied, it can be used as the basis and standard for diagnosis. Diagnosis is established if the results of regular retests still meet diagnostic criteria.

(2) Diagnostic standard for type 2 diabetes With reference to the diabetic cause cause standard published in Diabetes Care magazine in July 1997, the diagnostic standard for diabetes is satisfied and the insulin release test result satisfies one of the following conditions. , Diagnosed as type 2 diabetes.
(1) Insulin resistance with relative insulin deficiency (2) Significant insulin deficiency with insulin resistance

3. Selection criteria (1) Those whose age is between 18 and 65 years old (2) Informed consent (3) Those who meet the diagnostic criteria for type 2 diabetes (4) No gender restrictions

4. Excluded standards (1) Increased blood glucose level due to factors such as T1DM, pregnancy, drugs, etc. (2) Therapeutic effect judgment is affected by those who cannot judge the therapeutic effect by not taking the drug as prescribed or by incomplete data. (3) Patients participating in other drug clinical studies

5. Changes in blood glucose and glycated hemoglobin in both groups before and after treatment When the blood glucose and glycated hemoglobin in both groups before treatment were compared, there was no significant difference (P> 0.05), and there was comparability. The fasting blood glucose level and the postprandial blood glucose level of the patients in the treatment group and the control group after the treatment were both significantly decreased, and there was a significant difference in both of them as compared with those before the treatment (P <0.01). The improvement in fasting blood glucose level after treatment in the treatment group was significantly different from that in the control group (P <0.01), and the improvement in postprandial blood glucose level in the treatment group was significantly different from that in the control group. (P <0.05), and the improvement of glycated hemoglobin in the treatment group was significantly different from that in the control group (P <0.05) (see Table 3, FIG. 8, FIG. 9, and FIG. 10). )

6. Result analysis The fasting blood glucose level, postprandial blood glucose level, and glycated hemoglobin of the patients in the treatment group and the control group after the treatment were all significantly decreased, and there was a significant difference compared with the control group (P <0.05 or). P <0.01), it is shown that the blood glucose improving effect of the general Western drug + Chinese medicine prescription flora capsule for type 2 diabetes is higher than the blood glucose control effect of a single general Western drug.

Example 6: Clinical Example Based on the clinical effect of Example 5, the following typical cases are provided. The treatment plan for the case was to take 20 tablets twice a day, with 4 weeks as one treatment course and 3 treatment courses.

Case 1
Patient: Zhang, male, 72 years old. I have been suffering from "type 2 diabetes" for more than 30 years, and I took "glyclazide 30 mg qd, acarbose 50 mg tid" orally to control blood sugar, but the effect was not high, so I added "saxagliptin 5 mg qd" and took it. The fasting blood glucose level was controlled to 8.5-9.5 mmol / l, the postprandial blood glucose level was controlled to 10-12 mmol / l, and the glycated hemoglobin was controlled to 7-7.5%. He had a lot of dry mouth, was a little fat, had dry stools, was tired easily, had a bitter mouth, had a red tongue, had a yellow tongue coating, and had a weak string. When the Chinese herbal prescription bacterial flora capsule of the present invention was taken and treated for three treatment courses, the symptoms of bitter taste and fatigue were remarkably improved, and defecation became once a day. The fasting blood glucose level was controlled to around 7 mmol / l, the postprandial blood glucose level was controlled to around 8 mmol / l, and the glycated hemoglobin was controlled to 6.8%.

Case 2
Patient: Wang, female, 69 years old. He suffered from "type 2 diabetes" for 18 years and took "metformin 500 mg tid" orally to control blood glucose, but because the symptoms of the gastrointestinal tract were remarkable, he took "saxagliptin 5 mg qd, repaglinide 1 mg tid". Then, the fasting blood glucose level was controlled to 9-10 mmol / l, the postprandial blood glucose level was controlled to 9-12 mmol / l, and the saccharified hemoglobin was controlled to around 8.5%. Therefore, I have come to refrain from over-controlling food and drink. The hunger was remarkable, the stool was hungry, the stool was loose or hard, the stool was easy to get tired, the mouth was dry, the tongue was red and moss, and the number was fine. When the Chinese herbal prescription bacterial flora capsule of the present invention was taken and treated for three treatment courses, the feeling of hunger was significantly reduced, the feeling of fullness and the condition of stool were significantly improved, and the fasting blood glucose level was 6-. The postprandial blood glucose level was controlled to 9 mmol / l, the postprandial blood glucose level was controlled to around 10 mmol / l, and the glycated hemoglobin was controlled to 7.8%.

Case 3
Patient: Riku, male, 56 years old. After suffering from "type 2 diabetes" for 10 years and taking "metformin, saxagliptin" orally to control blood glucose, fasting blood glucose level is 8-10 mmol / l, postprandial blood glucose level is 9-11 mmol / l, and glycated hemoglobin. Was controlled to 7.7%. It was easy to get hungry and to have a stool because of heavy drinking. After taking the Kampo prescription bacterial flora capsule of the present invention and receiving treatment for three treatment courses, the dry mouth, satiety and stool conditions were significantly improved, and when metformin was stopped, the fasting blood glucose level increased. The postprandial blood glucose level was controlled to 6-7 mmol / l, the postprandial blood glucose level was controlled to around 9 mmol / l, and the glycated hemoglobin was controlled to 7.1%.

Case 4
Patient: Kim, a man, 81 years old. He has been suffering from "type 2 diabetes" for more than 30 years and has taken various hypoglycemic agents orally to control blood glucose, but the effect was not high. Five years ago, when I started taking "Novorin 30R (26u in the morning, 12u in the evening)" and "100 mg qd in the West" to control blood glucose, the fasting blood glucose level was 7-10 mmol / l. The postprandial blood glucose level was controlled to 8-14 mmol / l, and the glycated hemoglobin was controlled to around 7.5%. The blood glucose level fluctuated greatly, eating and drinking control was not good, it was easy to be anxious, lack of exercise, hungry, stool was once every 2-3 days, the tongue was red, the tongue coating was yellow, and the strings were. When the Chinese herbal formula capsule of the present invention was taken and treated for three treatment courses, the symptoms were significantly improved, the fasting blood glucose level was 6-9 mmol / l, and the postprandial blood glucose level was 9-10 mmol / l. Before and after, glycated hemoglobin was controlled to 6.4%. The daily dose of insulin was reduced by 4u.

Case 5
Patient: Lee, male, 43 years old. After suffering from "type 2 diabetes" for 3 years and taking "metformin 1000 mg / day" orally to control blood glucose, the fasting blood glucose level was good and the glycated hemoglobin was 6.5%, but the gastrointestinal tract. The symptoms were remarkable, the stomach was easy to get hungry, the stool was easy to get rid of, the tongue was light red and there were tooth marks, and the tongue coating was white. I didn't want to change my hypoglycemic drug for a while because my blood glucose was well controlled. When the Chinese herbal formula capsule of the present invention was taken and treated for three treatment courses, the feeling of fullness and stool was improved, and after stopping the administration of metformin, the glycated hemoglobin was 6.0%. ..

Case 6
Patient: Hayashi, male, 76 years old. He has been suffering from "type 2 diabetes" for 20 years and has been administered "insulin glargine, subcutaneous injection, 18u / day" + "acarbose, oral administration, 150mg / day" to control blood glucose, and his fasting blood glucose level is 6-8 mmol / l, postprandial blood glucose level is controlled to 8-12 mmol / l, blood glucose level 2 hours after breakfast is controlled to around 11 mmol / l, blood glucose level at other times is good, and glycated hemoglobin is 7.2. %, Drank a lot, had loose or hard stools, was sticky to the stool, had a small amount of moss on the tongue, and had a weak pulse. When the Chinese herbal formula capsule of the present invention was taken and treated for three treatment courses, the dry mouth and stool conditions were significantly improved, the body became comfortable, and the blood glucose level after breakfast was 7-10 mmol / l. , Saccharified hemoglobin was 7%.

Case 7
Patient: Lee, male, 51 years old. It's been a month since I was diagnosed with "type 2 diabetes". An elevated blood glucose level was discovered during a physical examination, the fasting blood glucose level became 12 mmol / l, and as a result of being examined for the etiology, "type 2 diabetes" was diagnosed, and glycated hemoglobin was 9.8%. At that time, thirst was remarkable, and at that time, "Novorapid 30, morning 22u, night 10u, subcutaneous injection" + "saxagliptin 5mg / day" was administered to control the blood glucose level, and in combination with the Chinese medicine prescription flora capsule of the present invention, After receiving three treatment courses, blood glucose control was good, thirst was significantly improved, and glycated hemoglobin was 6.4%.

Case 8
Patient: Zhang, female, 70 years old. It has been eight years since I was diagnosed with "type 2 diabetes". I am taking "repaglinide 1 mg tid" + "saxagliptin 5 mg qd" to control blood glucose, fasting blood glucose level is 7-8 mmol / l, postprandial blood glucose level is 8-11 mmol / l, and glycated hemoglobin is 7.3. The pulse was weak, with thirst, heavy stools, loose or hard stools, and a small amount of repaglinide. When taken in combination with the Chinese herbal formula capsule of the present invention and treated for three treatment courses, dry mouth and stool conditions were significantly improved, fasting blood glucose level was 6-8 mmol / l, and postprandial blood glucose. The value was 7-9 mmol / l and the glycated hemoglobin was 6.4%.

Case 9
Patient: Lu, female, 81 years old. It has been about 40 years since I was diagnosed with "type 2 diabetes". In order to control blood sugar, "Novorapid 30, 26u in the morning, 14u in the evening" was injected subcutaneously, the diet was irregular, and I ate a lot of snacks, so the blood sugar level was not well controlled and fluctuated greatly, 7 It is between -16 mmol / l, it is difficult to control the diet, glycated hemoglobin is 8.4%, there are complications with "diabetic retinopathy, peripheral neuropathy", and it is easy to drink a lot of mouth and get hungry. , Numbness of limbs, blurred vision, itchy skin, poor memory, prone to oral ulcers, constipation, pale yellow tongue, weak pulse. Instructed the use of insulin, adjusted the injection amount when overeating or high blood glucose level, used in combination with the Chinese herbal prescription flora capsule of the present invention, and received treatment of three treatment courses, dry mouth, visibility. Blurred skin, itchy skin were improved, stools were smooth, and it was difficult to change the diet, but the blood glucose level was 7-11 mmol / l and the glycated hemoglobin was 7%.

Case 10
Patient: Minami, male, 50 years old. It has been about 12 years since I was diagnosed with "type 2 diabetes". Taking "insulin glargine 20u / day subcutaneous injection" + "novonome, oral 1mg before meals" to control blood sugar, indigestion, easy stomach upset, possibility of gastroparesis 2 years ago It is thought that there is a blood sugar level that fluctuates between 6-13 mmol / l, and because it eats too much and does not digest food, it is easy to get hungry and may vomit, and defecation is irregular, and it takes 1-4 days. At one time, the stool was loose or hard, the tongue was light red with tooth marks, the tongue moss was white, and the pulse was weak. When I was instructed to eat regularly and received treatment for three treatment courses in combination with the Kampo prescription flora capsule of the present invention, the feeling of fullness was significantly reduced, vomiting stopped, and the stool condition changed. The blood glucose level was significantly improved to 6-11 mmol / l, and the glycated hemoglobin was 7.5%.

Case 11
Patient: Chan Mou, female, 67 years old. It has been about 20 years since I was diagnosed with "type 2 diabetes". I took a hypoglycemic drug orally, but because my blood glucose control was not good, I started to take "insulin glargine, subcutaneous injection at 14u / day" + "acarbose, chew 50mg before meals". By injecting insulin every day, the fasting blood glucose level is around 7 mmol / l, the postprandial blood glucose level is 9-10 mmol / l, and the glycated hemoglobin is 8%. However, after receiving three treatment courses, the anxiety was improved, the insulin glargine dose was reduced to 10 u / day, the fasting blood glucose level was around 7 mmol / l, and the postprandial blood glucose level was 7-9 mmol / l. The glycated hemoglobin was 7.5%.

Case 12
Patient: Zhang, a man, 37 years old. It was discovered that the blood sugar level had risen during a physical examination. After that, he was diagnosed with "type 2 diabetes". At the time of discovery, the fasting blood glucose level was 7.2 mmol / l, the postprandial blood glucose level was 10.0 mmol / l, and the glycated hemoglobin was 7.8%. After controlling eating and drinking, exercising in an appropriate amount, taking the Chinese herbal formula capsule of the present invention, and receiving treatment of three treatment courses, good hunger and dry mouth were improved, and the fasting blood glucose level was improved. The postprandial blood glucose level was around 6.5 mmol / l, the postprandial blood glucose level was around 8.0 mmol / l, and the glycated hemoglobin was 7.3%.

Claims (10)

A Chinese prescription bacterial flora capsule obtained by mixing a freeze-dried powder of a bacterial flora separated from feces and a Chinese herbal medicine extract powder obtained by extracting an active ingredient from a Chinese herbal medicine and crushing it. The Chinese prescription bacterial flora capsule according to claim 1, wherein the method for separating the bacterial flora from the feces is to separate the bacterial flora using a microorganism separating device in the luminal contents. The method for producing a freeze-dried powder of the flora isolated from the feces includes the following steps (1) to (4).
In step (1), a healthy donor's fecal sample is collected from a sterile sampling bottle, sealed and transferred to a sterile operation room, and is a sterile disposable consumables such as a filtration bottle, an AB bottle, a deodorizing bottle, a buffer bottle, and a bacterial solution bottle. Together with the intelligent fecal flora isolation system placed in series to collect the flora,
In step (2), physiological saline is added to the sampling bottle by the automatic liquid injection device of the liquid addition drive device, and the fecal sample is immersed.
In step (3), the air pump 2 is started so that the mixed bacterial solution in the sampling bottle passes through the filtration nets having different filtration values and collects in the buffer bottle, and the bacterial solution in the buffer bottle is further discharged by the bacterial solution drive device. After injecting into a bacterial solution bottle, the mixture is centrifuged, and after the centrifugation is completed, the supernatant is removed leaving a precipitate. The precipitate is a bacterial solution precipitate after separation and purification.
In step (4), glycerin is added to each centrifuge tube, mixed uniformly with a shaker, pre-frozen, the sample immediately after pre-freezing is lyophilized, and the lyophilized bacterial solution is dehydrated and lyophilized. The Chinese herbal formula capsule according to claim 2, wherein the powder is obtained. The Chinese herbal formula according to claim 3, wherein the sampling bottle is provided with a stirring rod, and the stool sample is stirred by the stirring rod in the sampling bottle so as to be sufficiently uniform in step (2). capsule. The volume ratio of the freeze-dried powder of the flora to the extracted powder of Chinese herbal medicine is 0.5-2: 1, preferably 1: 1.
Any one of claims 1 to 4, wherein the uniform mixing of the freeze-dried powder of the flora and the extracted powder of Chinese herbal medicine is carried out by mixing the two and then uniformly stirring the powder with a micromixer. The Chinese herbal formula capsule described in the section. The Chinese prescription flora capsule according to claim 5, further comprising filling an acid-resistant hypromerose capsule to obtain a Chinese prescription flora capsule. Any of claims 1 to 4, wherein the Chinese herbal medicine extract powder is obtained by extracting an active ingredient from a Chinese ginseng, yellow spirit, Jiuqu, Jiuqu, and Polygonatum sibi Chinese herbal formula and pulverizing it. Or the Chinese herbal prescription bacterial flora capsule described in item 1. The weight ratio of American ginseng, yellow spirit, Jiuqu, Jiuqu, and Polygonatum sibi in the Chinese prescription is 8-12: 12-18: 12-18: 8-12: 8-12, preferably 10 :. The Chinese herbal prescription flora capsule according to claim 7, characterized in that it is 15:15:10:10. The method for producing the Chinese herbal medicine extract powder includes the following steps (1) to (5).
In step (1), take the crude drug at a predetermined ratio, chop or crush it, put it in a decoction container, and put it in a decoction container.
In step (2), add water and soak.
In step (3), the mixture is heated to a boil, exuded, the decoction is separated, the crude drug residue is decoction 2-3 times by the usual method, and the decoction is collected.
In step (4), the decoction is extracted with alcohol, preferably ethanol.
The Chinese method according to claim 7, wherein in step (5), the alcohol-extracted filtrate is dried and then pulverized by an ultrafine pulverizer to pulverize it into an ultrafine powder of preferably less than 10 μm. Prescription bacterial flora capsule. Use of the Chinese herbal prescription flora capsule according to any one of claims 1 to 9 in the manufacture of a therapeutic agent for type 2 diabetes.

Images