阅读说明：本技术 一种治疗糖尿病的中药组合物及其制备方法和应用 (Traditional Chinese medicine composition for treating diabetes and preparation method and application thereof ) 是由 陶枫 高文澜 蔡淦 陈易 王雪菲 李斯斯 王文艳 于 2021-09-15 设计创作，主要内容包括：本发明涉及一种治疗糖尿病的中药组合物及其制备方法和应用,所述中药组合物由下列重量份配比的原料药制成：柴胡5-13份、枳实5-13份、葛根10-20份、升麻1-5份、黄芩5-13份、黄连2-10份、焦栀子5-13份、生白术5-13份、生黄芪10-20份、党参8-16份。本发明中药组合物符合“君臣佐使”配伍原则,不仅原料丰富易得,价格便宜,易于制备,并且能够从稳态上提高患者的降糖效果,具有临床优势和安全性,适合推广使用。(The invention relates to a traditional Chinese medicine composition for treating diabetes, a preparation method and an application thereof, wherein the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5-13 parts of radix bupleuri, 5-13 parts of immature bitter orange, 10-20 parts of radix puerariae, 1-5 parts of rhizoma cimicifugae, 5-13 parts of radix scutellariae, 2-10 parts of rhizoma coptidis, 5-13 parts of charred fructus gardeniae, 5-13 parts of raw rhizoma atractylodis macrocephalae, 10-20 parts of raw radix astragali and 8-16 parts of radix codonopsis. The traditional Chinese medicine composition accords with the compatibility principle of 'monarch, minister, assistant and guide', not only has rich and easily-obtained raw materials, low price and easy preparation, but also can improve the blood sugar reducing effect of patients from a steady state, has clinical advantages and safety, and is suitable for popularization and use.)

1. The traditional Chinese medicine composition for treating diabetes is characterized by comprising the following raw material medicines in parts by weight: 5-13 parts of radix bupleuri, 5-13 parts of immature bitter orange, 10-20 parts of radix puerariae, 1-5 parts of rhizoma cimicifugae, 5-13 parts of radix scutellariae, 2-10 parts of rhizoma coptidis, 5-13 parts of charred fructus gardeniae, 5-13 parts of raw rhizoma atractylodis macrocephalae, 10-20 parts of raw radix astragali and 8-16 parts of radix codonopsis.

2. The traditional Chinese medicine composition according to claim 1, which is prepared from the following raw materials in parts by weight: 7-11 parts of radix bupleuri, 7-11 parts of immature bitter orange, 13-18 parts of radix puerariae, 2-4 parts of cimicifugae foetidae, 7-11 parts of radix scutellariae, 4-8 parts of rhizoma coptidis, 7-11 parts of charred fructus gardeniae, 7-11 parts of raw rhizoma atractylodis macrocephalae, 13-18 parts of raw radix astragali and 10-14 parts of radix codonopsis.

3. The traditional Chinese medicine composition according to claim 2, which is prepared from the following raw materials in parts by weight: 9 parts of radix bupleuri, 9 parts of immature bitter orange, 15 parts of radix puerariae, 3 parts of rhizoma cimicifugae, 9 parts of radix scutellariae, 6 parts of rhizoma coptidis, 9 parts of charred fructus gardeniae, 9 parts of raw rhizoma atractylodis macrocephalae, 15 parts of raw radix astragali and 12 parts of radix codonopsis.

4. A preparation method of a traditional Chinese medicine composition for treating diabetes comprises the following steps: weighing the raw materials according to the weight part ratio, respectively crushing and uniformly mixing to obtain a medicine mixture, adding water which is 3-5 times of the total weight of the medicine mixture, decocting for 30-60 minutes by slow fire, filtering, and collecting filtrate.

5. The use of the Chinese medicinal composition according to any one of claims 1 to 3 for the preparation of a medicament for the treatment of diabetes.

6. The use according to claim 5, wherein said pharmaceutical dosage form is an oral formulation.

7. The oral preparation according to claim 6, wherein the oral preparation is in the form of granules, tablets, pills, powders, granules, oral liquids or capsules.

8. The use of claim 5, wherein the diabetes is type 2 diabetes.

Technical Field

The invention relates to the technical field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine composition for treating diabetes and a preparation method and application thereof.

Background

Type 2 diabetes (diabetes mellitus type 2, T2DM), known as noninsulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes (adult-onset diabetes), is a chronic metabolic disease that develops after the age of 35-40 years, accounting for more than 90% of diabetic patients. Patients are characterized by hyperglycemia, relative insulin deficiency, insulin resistance, and the like. Common symptoms are Polydipsia, pollakiuria, weight loss of unknown origin, and may also include polyphagia, tiredness, or soreness. Long-term complications from hyperglycemia include heart disease, stroke, diabetic retinopathy, which can lead to blindness, kidney failure, and even poor blood flow in the extremities requiring amputation, with few complications of diabetic ketoacidosis.

With the aging of the Chinese population and the change of life style, diabetes becomes an epidemic disease, and the prevalence rate rises dramatically from 0.67% in 1980 to 11.2% in 2020. The diabetes control and complications experiment (DCCT) and the uk prospective diabetes study (UKPDS) have established a basis for the relationship of glycemic control to chronic complications of diabetes, and glycated hemoglobin (HbA1c) is used as a gold standard for assessing glycemic control. However, as research progresses, there are many limitations to simply evaluating HbA1 c. The continuous development of glucose monitoring technology has led to the gradual introduction of the concept of Time-in-Range (TIR) within glucose targets. TIR refers to the time that a patient's glucose occupies 3.9-10mmol/L as a percentage of the entire day, and international consensus in 2019 suggests that TIR exceeding 70% is considered "good glycemic control".

Diabetes belongs to the category of diabetes in traditional Chinese medicine, and is firstly found in the "plain questions & strange diseases" of the internal channel: "the person must eat sweet and delicious food and is rich in fertilizer, the fat person is internally hot, the sweet person is full of the food, the qi of the food is reversed, and the food is converted into diabetes. Later doctors believe that the cause of diabetes is complex and is caused by yin fluid consumption such as insufficient endowment, improper diet, emotional disorder, excessive desire and the like. It is mainly caused by yin-fluid deficiency with predominant dryness-heat, while yin-deficiency is the primary cause and dryness-heat is the secondary cause. Lidongyuan is one of four major golden units, and the theory that the spleen and the stomach are injured internally and the diseases are caused by the birth is advocated in academia. According to the Chua ceramic professor of Chinese medicine, a unique way is developed, and the diabetes is considered to be caused by weakness of the spleen and the stomach and internal yin fire. Yin fire is caused by deficiency of the spleen and stomach primordial qi, resulting from overeating, internal injury of seven emotions, while fire of the heart monarch, hyperactivity of liver-kidney fire and yang qi depression are marked by fire transformation, so thirst-quenching symptoms such as thirst and polydipsia are seen. The spleen and stomach tonifying, yin fire purging and yang ascending soup is the first prescription in the spleen and stomach theory written by Lidongyuan, and the records in the spleen and stomach theory and the spleen and stomach prosperity and defecation theory are as follows: food impairs the stomach, overstrain impairs the spleen, and deficiency of the spleen and stomach causes fire pathogen to produce large heat. In addition, the combination of damp and heat, the deficiency of yang qi in the day, the failure of yang qi to ascend … …, the generation of … … diseases caused by the weakness of spleen and stomach, the latter prescription, the decoction for reinforcing spleen and stomach, purging yin fire and ascending yang, is called spleen-stomach-reinforcing, yin-fire-purging and yang-ascending decoction. "

Chinese patent document CN107789506A discloses a Chinese medicinal composition for treating diabetes. 15-20g of astragalus membranaceus, 15-20g of codonopsis pilosula, 15-20g of radix rehmanniae, 6-9g of cape jasmine fruit, 10-15g of dogwood, 20-30g of Chinese yam, 10-15g of radix ophiopogonis, 10-15g of achyranthes bidentata, 5-10g of rhizoma alismatis, 10-15g of mulberry leaf, 20-50g of corn stigma, 10-15g of radix puerariae and 15-20g of wolfberry fruit, extracting with ethanol, distilling, concentrating and preparing into 20g of granular preparation. The Chinese medicinal composition has no toxic or side effect, and can effectively treat type 1 and type 2 diabetes caused by pancreatic islet beta cell function reduction or pancreatic islet beta cell reduction, insulin resistance and the like. Has obvious effect, is economical and simple. The traditional Chinese medicine composition overcomes the application limitation and the deficiency of the existing treatment of type 1 and type 2 diabetes, opens a new door for the wide application of the traditional Chinese medicine composition, and is suitable for popularization and promotion. Chinese patent document CN108042710A discloses a traditional Chinese medicine composition for treating qi-yin deficiency and damp-heat internal accumulation type 2 diabetes, which is prepared from the following raw material medicines: codonopsis pilosula, astragalus membranaceus, Chinese yam, rhizoma polygonati, coptis chinensis, radix puerariae, bighead atractylodes rhizome and poria cocos. Said invention also provides the application of said Chinese medicine composition and its preparation. Its advantages are: the traditional Chinese medicine composition is proper in compatibility, and can effectively treat type 2 diabetes under the comprehensive action of the traditional Chinese medicine raw materials. However, the traditional Chinese medicine composition for treating diabetes and the preparation method and application thereof are not reported at present.

Disclosure of Invention

The invention aims to provide a traditional Chinese medicine composition for treating diabetes aiming at the defects in the prior art.

The invention further aims to provide a preparation method of the traditional Chinese medicine composition.

Another object of the present invention is to provide the use of the said Chinese medicinal composition.

In order to achieve the purpose, the invention adopts the technical scheme that:

a traditional Chinese medicine composition for treating diabetes comprises the following raw material medicines in parts by weight: 5-13 parts of radix bupleuri, 5-13 parts of immature bitter orange, 10-20 parts of radix puerariae, 1-5 parts of rhizoma cimicifugae, 5-13 parts of radix scutellariae, 2-10 parts of rhizoma coptidis, 5-13 parts of charred fructus gardeniae, 5-13 parts of raw rhizoma atractylodis macrocephalae, 10-20 parts of raw radix astragali and 8-16 parts of radix codonopsis.

Preferably, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 7-11 parts of radix bupleuri, 7-11 parts of immature bitter orange, 13-18 parts of radix puerariae, 2-4 parts of cimicifugae foetidae, 7-11 parts of radix scutellariae, 4-8 parts of rhizoma coptidis, 7-11 parts of charred fructus gardeniae, 7-11 parts of raw rhizoma atractylodis macrocephalae, 13-18 parts of raw radix astragali and 10-14 parts of radix codonopsis.

More preferably, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 9 parts of radix bupleuri, 9 parts of immature bitter orange, 15 parts of radix puerariae, 3 parts of rhizoma cimicifugae, 9 parts of radix scutellariae, 6 parts of rhizoma coptidis, 9 parts of charred fructus gardeniae, 9 parts of raw rhizoma atractylodis macrocephalae, 15 parts of raw radix astragali and 12 parts of radix codonopsis.

In order to achieve the second object, the invention adopts the technical scheme that:

the preparation method of any one of the above traditional Chinese medicine compositions comprises the following steps: weighing the raw materials according to the weight part ratio, respectively crushing and uniformly mixing to obtain a medicine mixture, adding water which is 3-5 times of the total weight of the medicine mixture, decocting for 30-60 minutes by slow fire, filtering, and collecting filtrate.

In order to achieve the third object, the invention adopts the technical scheme that:

the application of any one of the traditional Chinese medicine compositions in preparing a medicament for treating diabetes is disclosed.

Preferably, the pharmaceutical dosage form is an oral formulation.

More preferably, the oral preparation is in the form of granules, tablets, pills, powder, granules, oral liquid or capsules.

Preferably, the diabetes is type 2 diabetes.

The invention has the advantages that:

1. the traditional Chinese medicine composition accords with the compatibility principle of 'monarch, minister, assistant and guide', the bupleurum is used as the monarch in the prescription to promote gallbladder qi, promote dispersion and excretion and promote the transportation and transformation of spleen and stomach, and as in 'the theory of spleen and stomach, the transmission and transformation theory of deficiency and excess of spleen and stomach', the gallbladder qi rises in spring, and the excess and viscera are also increased in spring; the combination of the largetrifoliolious bugbane rhizome and the kudzuvine root is added to help the spleen and stomach qi rise, transport and transform again and benefit the pivot mechanism, aiming at treating sinking of spleen yang; the astragalus, the codonopsis pilosula and the bighead atractylodes rhizome are used as ministerial drugs, and the qi and the spleen are invigorated, the wind-evil is used for ascending, the spleen is vigorous, the yang is cleared, and the yin fire is not generated; the scutellaria baicalensis, the coptis chinensis and the scorched gardenia are used as ministerial drugs and adjuvant drugs for clearing heat, drying dampness and purging yin fire, and the immature bitter orange is used for promoting qi circulation and removing food retention, so that the effects of tonifying spleen and stomach, ascending yang qi and purging yin fire are achieved together. The formula combines cold and heat, performs purgation and tonification simultaneously, is clinically applicable to the syndrome of deficiency and excess mixed with cold and heat mixed with each other with spleen failure as the main cause and liver and stomach stagnated heat as the main cause, and the whole formula also follows the principle of 'in Dujing' that only the formula of sweet and warm is used for tonifying yang and the formula of sweet and cold is used for purging fire to heal.

2. The composition and the proportion of the traditional Chinese medicine composition are obtained based on a large number of experiments, and the treatment effect is most prominent.

3. The traditional Chinese medicine composition has the advantages of abundant and easily-obtained raw materials, low price, easy preparation and suitability for popularization and use.

Detailed Description

EXAMPLE 1 preparation of the Chinese medicinal composition of the present invention

Weighing 9 parts of radix bupleuri, 9 parts of immature bitter orange, 15 parts of radix puerariae, 3 parts of rhizoma cimicifugae, 9 parts of radix scutellariae, 6 parts of rhizoma coptidis, 9 parts of charred fructus gardeniae, 9 parts of raw rhizoma atractylodis macrocephalae, 15 parts of raw radix astragali and 12 parts of radix codonopsis pilosulae according to the weight part ratio.

Example 2 preparation of the Chinese medicinal composition of the present invention

Weighing 5 parts of radix bupleuri, 5 parts of immature bitter orange, 10 parts of radix puerariae, 1 part of cimicifugae foetidae, 5 parts of radix scutellariae, 2 parts of rhizoma coptidis, 5 parts of charred fructus gardeniae, 5 parts of raw rhizoma atractylodis macrocephalae, 10 parts of raw radix astragali and 8 parts of radix codonopsis pilosulae according to the weight part ratio.

Example 3 preparation of the Chinese medicinal composition of the present invention

Weighing 13 parts of radix bupleuri, 13 parts of immature bitter orange, 20 parts of radix puerariae, 5 parts of rhizoma cimicifugae, 13 parts of radix scutellariae, 10 parts of rhizoma coptidis, 13 parts of charred fructus gardeniae, 13 parts of raw rhizoma atractylodis macrocephalae, 20 parts of raw radix astragali and 16 parts of radix codonopsis pilosulae according to the weight part ratio.

Example 4 preparation of the Chinese medicinal composition of the present Invention (IV)

Weighing 7 parts of radix bupleuri, 7 parts of immature bitter orange, 13 parts of radix puerariae, 2 parts of rhizoma cimicifugae, 7 parts of radix scutellariae, 4 parts of rhizoma coptidis, 7 parts of charred fructus gardeniae, 7 parts of raw rhizoma atractylodis macrocephalae, 13 parts of raw radix astragali and 10 parts of radix codonopsis pilosulae according to the weight part ratio.

Example 5 preparation of the Chinese medicinal composition of the present invention (V)

Weighing 11 parts of radix bupleuri, 11 parts of immature bitter orange, 18 parts of radix puerariae, 4 parts of rhizoma cimicifugae, 11 parts of radix scutellariae, 8 parts of rhizoma coptidis, 11 parts of charred fructus gardeniae, 11 parts of raw rhizoma atractylodis macrocephalae, 18 parts of raw radix astragali and 14 parts of radix codonopsis pilosulae according to the weight part ratio.

Example 6 preparation of the Chinese medicinal composition of the present invention (VI)

Weighing 12 parts of radix bupleuri, 12 parts of immature bitter orange, 15 parts of radix puerariae, 3 parts of rhizoma cimicifugae, 12 parts of radix scutellariae, 6 parts of rhizoma coptidis, 12 parts of charred fructus gardeniae, 12 parts of raw rhizoma atractylodis macrocephalae, 15 parts of raw radix astragali and 12 parts of radix codonopsitis according to the weight part ratio.

EXAMPLE 7 preparation of the Chinese medicinal composition of the present invention (VII)

Weighing 10 parts of radix bupleuri, 10 parts of immature bitter orange, 15 parts of radix puerariae, 3 parts of rhizoma cimicifugae, 10 parts of radix scutellariae, 6 parts of rhizoma coptidis, 10 parts of charred fructus gardeniae, 10 parts of raw rhizoma atractylodis macrocephalae, 15 parts of raw radix astragali and 12 parts of radix codonopsis pilosulae according to the weight part ratio.

EXAMPLE 8 preparation of the Chinese medicinal composition of the present invention (eight)

Weighing 9 parts of radix bupleuri, 9 parts of immature bitter orange, 13 parts of radix puerariae, 3 parts of rhizoma cimicifugae, 9 parts of radix scutellariae, 6 parts of rhizoma coptidis, 9 parts of charred fructus gardeniae, 9 parts of raw rhizoma atractylodis macrocephalae, 13 parts of raw radix astragali and 12 parts of radix codonopsis pilosulae according to the weight part ratio.

Example 9 preparation of the Chinese medicinal composition of the present invention (nine)

Weighing 9 parts of radix bupleuri, 9 parts of immature bitter orange, 15 parts of radix puerariae, 5 parts of rhizoma cimicifugae, 9 parts of radix scutellariae, 6 parts of rhizoma coptidis, 9 parts of charred fructus gardeniae, 9 parts of raw rhizoma atractylodis macrocephalae, 15 parts of raw radix astragali and 12 parts of radix codonopsis pilosulae according to the weight part ratio.

EXAMPLE 10 preparation of the Chinese medicinal composition of the present invention (Ten)

Weighing 6 parts of radix bupleuri, 6 parts of immature bitter orange, 15 parts of radix puerariae, 3 parts of rhizoma cimicifugae, 6 parts of radix scutellariae, 6 parts of rhizoma coptidis, 6 parts of charred fructus gardeniae, 6 parts of raw rhizoma atractylodis macrocephalae, 15 parts of raw radix astragali and 12 parts of radix codonopsis pilosulae according to the weight part ratio.

EXAMPLE 11 preparation of an aqueous decoction of the Chinese medicinal composition of the present invention (eleven)

Weighing the raw materials according to the weight part ratio of any one of embodiments 1-10, mixing uniformly, adding 3-5 times of water, decocting with slow fire for 30-60 minutes, filtering with two layers of medical gauze, and collecting filtrate to obtain the water decoction.

Example 12 preparation of granules of the Chinese medicinal composition of the present invention (twelve)

Weighing the raw materials according to the weight part ratio of any one of embodiments 1-10, adding water, decocting for 3 times, combining filtrates, and concentrating to obtain a fluid extract with a relative density of 1.1. Adding ethanol into the fluid extract, standing for 24 hours, filtering, recovering ethanol, and concentrating to obtain a thick paste with a relative density of 1.2. Spray drying the soft extract to obtain dry extract fine powder. Adding dextrin into the dry extract fine powder, mixing, granulating by conventional method, drying, and making into granule.

Example 13 preparation of a tablet of the Chinese medicinal composition of the present invention (thirteen)

Weighing the raw materials according to the weight part ratio of any one of embodiments 1-10, adding water, decocting for 3 times, combining filtrates, and concentrating to obtain a fluid extract with a relative density of 1.1. Spray drying the fluid extract to obtain dry extract fine powder. Mixing the dry extract fine powder with sodium carboxymethyl starch and microcrystalline cellulose, granulating by conventional method, drying, adding magnesium stearate and silicon dioxide, mixing, tabletting by conventional method, and making into dispersible tablet.

Example 14 preparation of a Capsule of the Chinese medicinal composition of the present invention (fourteen)

Weighing the raw materials according to the weight part ratio of any one of embodiments 1-10, adding water, decocting for 3 times, combining filtrates, and concentrating to obtain a fluid extract with a relative density of 1.15. Spray drying the fluid extract to obtain dry extract fine powder. Adding magnesium stearate and pulvis Talci, mixing, adding hollow capsule by conventional method, and making into capsule.

Example 15 preparation of the Chinese medicinal composition drop pill of the invention (fifteen)

Weighing the raw materials according to the weight part ratio of any one of embodiments 1-10, adding water, decocting for 3 times, combining filtrates, and concentrating to obtain fluid extract with relative density of 1.18. Spray drying the fluid extract to obtain fine powder. Adding appropriate amount of water or/and yellow wine, and making into watered pill. Or adding appropriate amount of ethanol and soybean oil to make soft mass, making into pill with pellet making machine, drying, sieving, and making into pellet. Or making dripping pill with polyethylene glycol as matrix and dimethyl silicone oil as condensate.

EXAMPLE 16 preparation of oral liquid of Chinese medicinal composition of the present invention (sixteen)

Weighing the raw materials according to the weight part ratio of any one of embodiments 1-10, adding water, decocting for 3 times, combining filtrates, and concentrating to obtain a fluid extract with a relative density of 1.1. Adding ethanol into the fluid extract, standing for 24 hours, filtering, recovering ethanol, and concentrating to obtain a thick paste with a relative density of 1.2. Dissolving stevioside in pure water by conventional method, adding sodium benzoate and purified water, mixing with the soft extract, and making into oral liquid.

EXAMPLE 17 clinical trials of the Chinese medicinal composition of the present invention

1 clinical data

Diagnostic criteria:

western diagnostic criteria: referring to the diagnosis standard of type 2 diabetes mellitus in the Chinese medical society diabetes mellitus prevention and treatment guidelines for type 2 diabetes mellitus (2020 edition), typical diabetes symptoms plus random blood sugar is more than or equal to 11.1mmol/L, plus fasting blood sugar (FPG) is more than or equal to 7.0mmol/L, plus OGTT 2h blood sugar is more than or equal to 11.1mmol/L, plus HbA1c is more than or equal to 6.5%, and people without typical diabetes symptoms need to be reviewed and confirmed every day.

The traditional Chinese medicine diagnosis standard is as follows: referring to the diagnosis standard of diabetes in the clinical research guiding principle of new traditional Chinese medicine for treating diabetes and dialectically belonging to the syndrome of liver-stomach stagnated heat, the main symptoms are thirst with desire for drink, frequent urination, shortness of breath and no speaking desire, abdominal fullness and distention, and head and body sleepiness; the secondary symptoms are uncomfortable defecate, frequent defecate, lassitude and hypodynamia, greasy and yellow tongue coating, and wiry and slippery or thready and slippery pulse. Scoring criteria are shown in table 1.

TABLE 1 evaluation of the Chinese medicine symptom integrals

1.1 inclusion criteria

1) The above-mentioned Western diagnosis standard is met; 2) according with the diagnosis standard of the traditional Chinese medicine, the syndrome is distinguished as liver-stomach stagnated heat type; 3) the patient T2DM who is seen at the outpatient clinic of the traditional Chinese medical hospital in Shanghai city is 18-85 years old, and the patient whose basic drug is metformin and sulfonylureas drug for reducing blood sugar and whose glycosylated hemoglobin is 7.0-8.5%; 4) voluntarily attend and sign an informed consent.

1.2 exclusion criteria

Serious diabetic complications, severe infectious diseases, serious liver and kidney insufficiency, acute cardiovascular and cerebrovascular diseases, and psychosis patients; patients taking other blood glucose affecting drugs during the test period; type 1 diabetes patients, pregnant or lactating women, allergic people; non-author (exit halfway or bad fit).

1.3 general data

T2DM patients who are treated by the department of endocrinology in Shanghai city of traditional Chinese medicine hospital in 2 months-12 months in 2020 are collected and divided into an observation group and a control group according to a random digital table method, wherein 53 cases are used in each group. After the clinical observation, 1 treatment group and 2 control groups were dropped, and finally 103 statistical collections were included. Observation group 52 cases, age 32-85 years; 51 cases of the control group; age 34-81 years; compared with general data (age, sex, course of disease, weight, BMI, FPG, 2 hPGG, HbA1c and FINS) between two groups, the difference has no statistical significance (P is more than 0.05) and is comparable. Clinical trial registration number (ChiCTR1800019287) was obtained for this study.

TABLE 2 comparison of baseline data between test and control patients

Note: BMI is body mass index; FPG is fasting blood glucose; 2 hPGG is 2h blood sugar after meal; HbA1c is glycated hemoglobin; FINS is fasting insulin; HOMA-IR assesses the insulin resistance index for a steady state model.

2 method

2.1 methods of treatment

The two groups of patients are subjected to basic treatment of diabetes, including diet control and exercise treatment, the basic drugs of the diabetes are metformin and sulfonylureas drugs (including glimepiride, gliclazide sustained release tablets, gliquidone, glipizide sustained release tablets and the like) for reducing blood sugar, and the basic drugs of the patients are all taken in the original dosage.

TABLE 3 comparison of two groups of basal medications

Observation group: the traditional Chinese medicine composition (liver-clearing, spleen-tonifying and blood sugar-reducing drink) is used for treatment, and the formula is as follows: 9 parts of radix bupleuri, 9 parts of immature bitter orange, 15 parts of radix puerariae, 3 parts of rhizoma cimicifugae, 9 parts of radix scutellariae, 6 parts of rhizoma coptidis, 9 parts of charred fructus gardeniae, 9 parts of raw rhizoma atractylodis macrocephalae, 15 parts of raw radix astragali and 12 parts of radix codonopsis. Is decocted from the Chinese medicinal preparation of the hospital, and is taken 1 dose/day in the morning and evening before meals.

Control group: sitagliptin phosphate (jirang, msonid, 1 time daily, 100mg each) was added for oral administration.

Both groups of patients were treated for 12 weeks.

2.2 Observation indicators and methods

2.2.1 integration of Chinese medicine syndrome

The symptom score evaluation details are shown in table 1. The dose was 1 time before and after treatment.

2.2.2 assessment of blood glucose indicators

Collecting 2ml of early morning fasting venous blood and 2h postprandial venous blood of a patient, centrifuging, taking upper serum, and detecting Fasting Blood Glucose (FBG) and postprandial 2-hour blood glucose (PBG) by a dry chemical method (GOD oxidase method). HbA1c levels were measured by chromatography, and 2mL of venous blood was drawn from the patient on an empty stomach early in the morning and placed in EDTA anticoagulant tubes. The blood glucose standard-reaching rate (HbA1c is less than 7%) is calculated after the treatment course is finished and 1 time of detection is carried out before and after the treatment course.

2.2.3 dynamic blood glucose monitoring index and blood glucose variability variation

The monitoring system consists of a disposable blood glucose sensor (MQ-GS type), a blood glucose emitter (MQ-TS type), a blood glucose receiver (MQ-RS type) and user analysis software (MQ-RGMS type). Blood glucose monitors were from lake meiqi medical devices ltd [ product model: RGMS-1, national mechanical notes: 20173400694]. Recording blood sugar value for 1 time every 3min, transmitting the blood sugar value to a blood sugar receiver through a subcutaneous sensing electrode, continuously monitoring for 72h, and setting the installation day as a system debugging day. The dynamic blood sugar monitoring observation indexes comprise: MBG (mean blood glucose), TIR (TIR is defined as the percentage of time glucose is in the range of 3.9-10.0mmol/L over 24 h), TAR, TBR; the blood glucose variability includes: CV (coefficient of variation), SDBG (standard deviation of glucose), MAGE (mean amplitude of effective fluctuation). A generalized TIR may include the time that glucose is in different ranges, theoretically including the time ratio of glucose above the target range for a time ≧ 11.1mmol/L (TAR) and glucose below the target range for a time ≦ 3.9mmol/L (TBR), which may be used to assess the patient's hyperglycemic and hypoglycemic conditions, respectively.

2.2.4 Fasting Insulin (FINS) levels and insulin resistance index

2mL of fasting elbow venous blood of a patient is extracted before and after treatment, centrifuged at 4000r/min for 10min, serum is separated and stored in a refrigerator at the temperature of-20 ℃ for examination, Fasting Insulin (FINS) level is detected by adopting a Roche electroluminescence method, and an insulin resistance index (HOMA-IR) is calculated according to FPG and FINS values.

HOMA-IR＝(FINS×FPG)/22.5。

2.2.5 safety observations

The blood routine, urine routine, liver function, renal function and the like of the patients are detected before and after treatment, and adverse reactions in the two groups of treatment processes are recorded.

2.3 statistical methods

Statistical analysis was performed using SPSS 25.0 software. Normally distributed metrology data toRepresenting that the comparison between groups adopts two samples to carry out t test independently, and the paired data adopts paired t test; the counting data are expressed by examples, and x is adopted for comparison²And (6) checking. The difference is statistically significant when P is less than 0.05And (5) defining.

3 results

3.1 changes in the syndrome integrals of TCM

The integral of the traditional Chinese medicine symptoms of the two groups before treatment has no obvious difference; the symptom scores of the two groups are reduced after treatment, and the two groups have statistical significance compared with the symptoms before treatment; the score of the observation group after treatment is obviously lower than that of the control group (P <0.05), which indicates that the score of the symptom of the patient is obviously better than that of the sitagliptin group by adding the traditional Chinese medicine group, and the result is shown in a table 4.

TABLE 4 integral comparison of Chinese medicine syndrome before and after treatment of two groups of type 2 diabetic patients

Note: p <0.05 compared to the group before treatment; compared with the control group after the treatment,^△P＜0.05。

3.2 comparison of post-treatment glycemic compliance rates

Although the patient's actual management goals are individualized, the criteria used to assess the effects are generally not taken into account for the specific individualized goals, but rather are the general control criteria required by the guidelines. The result shows that the standard reaching rate of the glycated hemoglobin of the observed group is 46.2 percent and is higher than 23.5 percent of the control group (P is less than 0.05), and the result is shown in a table 5.

TABLE 5 comparison of blood glucose standards after treatment [ n (%) ]

3.3 post-treatment two groups of dynamic blood glucose indicators and blood glucose variability changes

The MAGE, TIR, TAR and TBR of the two groups before treatment have no obvious difference, and the two groups after treatment are obviously improved and have statistical significance compared with the groups before treatment; after treatment, the P values of the two groups of patients with MAGE, TIR, TAR and TBRV were all greater than 0.05, and the differences were not statistically significant, as shown in table 6.

TABLE 6 comparison of dynamic blood glucose index and blood glucose variability after treatment of two groups of type 2 diabetic patients

Note: p <0.05 compared to the group before treatment; compared with the control group after the treatment,^△P＜0.05。

3.4 comparison of blood glucose levels

FPG, 2 hPGG and HbA1c levels were significantly reduced after treatment in both groups (P was <0.05), and there was no statistical difference between the two groups after treatment, as shown in Table 7.

TABLE 7 comparison of blood glucose index levels before and after treatment for two groups of type 2 diabetic patients

Note: p <0.05 compared to the group before treatment; compared with the control group after the treatment,^△P＜0.05。

3.5 comparison of Fasting Insulin (FINS) levels and insulin resistance index

Both the FINS levels and the HOMA-IR were significantly reduced after treatment (P was <0.05) compared to pre-treatment in both groups, and there was no significant difference between the two groups after treatment, see table 8.

TABLE 8 comparison of pancreatic islet beta cell function indices before and after treatment in two groups of patients

Note: p <0.05 compared to the group before treatment; compared with the control group after the treatment,^△P＜0.05。

3.6 comparison of adverse reaction occurrence conditions of two groups of patients

The observation group had no adverse reaction. Patients in the control group suffered from mild nausea in 2 cases, and the symptoms were relieved by themselves along with the treatment; 1 case of transient diarrhea appeared on the 3 rd day of treatment, which improved itself the following day. The adverse reactions of two groups of patients are compared, and the difference is not statistically significant (P is more than 0.05), which is shown in Table 9.

TABLE 9 comparison of adverse reaction of hypoglycemic drugs in two groups [ n (%) ]

Discussion 4

The experiment shows that the traditional Chinese medicine syndrome scores of the observation group are obviously superior to those of the control group in the standard reaching rate of blood sugar; after treatment, the water levels of FPG, 2 hPGA, HbA1c, FINS and HOMA-IR in the two groups are obviously reduced compared with those before treatment, and the difference between the two groups after treatment is not found; after treatment, MAGE, TIR, TAR and TBR in the two groups are obviously improved compared with before treatment, and the two groups have no obvious difference after treatment; the curative effect of the liver-clearing spleen-tonifying blood-glucose-reducing drink is equivalent to that of sitagliptin, the TIR level can be effectively improved when the liver-clearing spleen-tonifying blood-glucose-reducing drink is used for treating type 2 diabetes, the blood-glucose-reducing effect of a patient is improved from a steady state, and the liver-clearing spleen-tonifying blood-glucose-reducing drink has clinical advantages and safety. The comparison of blood glucose levels and TIR between the two groups after treatment did not reach statistical differences, which may be related to insufficient treatment time, resulting in insufficient differences in treatment results.

The Chinese medicinal composition takes the radix bupleuri as a monarch, promotes gallbladder qi, relieves diarrhea, promotes the transportation, transformation and lifting of spleen and stomach, and just as in the 'gallbladder qi spring rising in the theory of spleen and stomach and the transmission and transformation theory of deficiency and excess of spleen and stomach', the rest internal organs follow the gallbladder qi spring rising; the combination of the largetrifoliolious bugbane rhizome and the kudzuvine root is added to help the spleen and stomach qi rise, transport and transform again and benefit the pivot mechanism, aiming at treating sinking of spleen yang; the astragalus, the codonopsis pilosula and the bighead atractylodes rhizome are used as ministerial drugs, and the qi and the spleen are invigorated, the wind-evil is used for ascending, the spleen is vigorous, the yang is cleared, and the yin fire is not generated; the scutellaria baicalensis, the coptis chinensis and the scorched gardenia are used as ministerial drugs, the assistant drugs are used for clearing heat, eliminating dampness and purging yin fire, and the immature bitter orange is used for promoting qi circulation and removing food retention, so that the effects of tonifying spleen and stomach, ascending yang qi and purging yin fire are achieved. The formula combines cold and heat, performs purgation and tonification simultaneously, is clinically applicable to the syndrome of deficiency and excess mixed with cold and heat mixed with each other with spleen failure as the main cause and liver and stomach stagnated heat as the main cause, and the whole formula also follows the principle of 'in Dujing' that only the formula of sweet and warm is used for tonifying yang and the formula of sweet and cold is used for purging fire to heal. In recent western medicine research, inflammatory reaction and oxidative stress reaction are involved in the generation and development of T2DM, and abnormal expression of inflammatory factors and oxygen radicals can cause infiltration of adipose tissue macrophages and block insulin signal conduction pathways, thereby leading to insulin resistance and blood sugar increase. The astragalus and the codonopsis pilosula can enhance immune response and inhibit hyperthyroidism; cimicifugae rhizoma and bupleuri radix for relieving inflammation; a large number of animal and clinical researches show that the scutellaria baicalensis, the coptis chinensis and the fructus gardeniae preparatus have good treatment effects on metabolic diseases, wherein the berberine can promote insulin secretion, improve insulin resistance, inhibit fat synthesis, relieve adipose tissue fibrosis, reduce hepatic steatosis, improve intestinal microbial environment and the like. The traditional Chinese medicine composition of the invention can play a role in reducing blood sugar in various inflammation pathways.

The above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and additions can be made without departing from the method of the present invention, and these modifications and additions should also be regarded as the protection scope of the present invention.