CN102366497B - Medicinal compound preparation for treating diabetes and preparation method of medicinal compound preparation - Google Patents

Abstract

The invention discloses a medicinal compound preparation for treating diabetes, which comprises diformin, Chinese atractylodes, figwort, mulberry leaves, ginkgo leaves, rhizoma alismatis and common fenugreek seed. A clinically acceptable formulation is prepared by using the method of decoction with water, regurgitation and extraction with ethanol and purification with macroporous resin. The compound preparation has a good curative effect in the aspect of treating diabetes.

Description

A kind of drug compound preparation for the treatment of diabetes and preparation method thereof

Technical field

The present invention relates to a kind of drug compound preparation, particularly relate to a kind of compound preparation that is formed by metformin hydrochloride and Chinese medicine, and the preparation method of this compound preparation and the application in the treatment diabetes.The invention belongs to field of medicaments.

Background technology

Modernization and social aging along with socioeconomic development, scientific and technological progress, living standard raising, life pattern, no matter developed country or developing country, the sickness rate of diabetes is all increasing year by year, and diabetes have become the 3rd serious main Chronic Non-Communicable Diseases after tumor, cardiovascular and cerebrovascular disease.The data of World Health Organization (WHO) (WHO) shows, 1997 annual reports, and whole world diabetics 1.35 hundred million, wherein 90% is type 2 diabetes mellitus, estimates that to 2025 the ill number of global diabetes will reach 300,000,000, increases at present nearly twice.The survey result that 2007-2008 carries out in the whole nation shows, China's diabetes prevalence is 9.7%, the prevalence of prediabetes (impaired glucose tolerance and impaired fasting glucose (IFG)) reaches 15.5%, and in prediction on such basis, national diabetes number of patients has 9,000 ten thousand approximately.

Diabetes are a kind of chronic diseases, are characterized in that the course of disease is long, the state of an illness is complicated, complication is many, the fatality rate height of disabling.According to statistics, the died that causes of the concurrent cardiovascular and cerebrovascular disease of diabetics accounts for 80% of dead sum.Diabetics merges blood fat rising person and accounts for more than 80%, and blood viscosity rising person reaches 90%.

Diabetes are divided into type 1 diabetes and two kinds of fundamental types of type 2 diabetes mellitus: type 1 diabetes (insulin-dependent diabetes, insulin-dependent diabetes mellitus, IDDM) pathogenesis mainly be because the beta Cell of islet autoimmune disease (allergy of IV type causes) due to virus, the chemical substance in heredity and the environmental factors; Type 2 diabetes mellitus (non-insulin-dependent, non-insulin-dependent diabetes mellitus, NIDDM) pathogenesis is main to be increased with defect of insulin secretion, glycogen (HGO) output and the factor such as insulin resistant (IR) is relevant on every side, and now research finds that it also suddenlys change relevant with several genes.

Diabetes are complex diseases because of syndrome, be since in the body hormone of insulin deficit or antagonism insulin increase, or insulin can not be brought into normal play physiological action and a kind of general, the chronic progressive disease of the water power medium metabolism disorder of the glucose, protein and the lipid metabolic disorder that cause and secondary in target cell.It is characterized by the unusual rising of concentration of glucose and glucose in urine in the blood circulation, occur typical three-many-one-little symptom when blood glucose is too high, i.e. polydipsia, polyuria, polyphagia and lose weight, and with fatigue and weak.

Present most of type 2 diabetes mellitus patient does not have typical diabetic symptom, have in addition have no any subjective symptoms, usually be in the generaI investigation of health examination or diabetes, to find blood sugar increasing, be diagnosed as diabetes.It should be noted that, though diabetes are chronic diseases, if but can not get treating timely, the blood glucose long-term control is bad, but coronary heart disease then, hypertension, diabetic hyperlipidemia, cerebrovascular, nephropathy, ocular complications (retinopathy, cataract, ametropia, diabetic eye muscular nerve pathological changes etc.), neuropathy (peripheral neuropathy, vegetative nerve lesion and central neuropathy), diabetic foot, diabetic dermopathy, diabetic impotence etc., ketoacidosis can occur in severe patient, the hypertonicity diabetic coma, and easily merge multi-infection, had a strong impact on patient's health and quality of life.

Diabetes are not only abnormal carbohydrate metabolism, and disorders of lipid metabolism has important effect to diabetes and complication.Many studies confirm that, adiposis patient as far back as carbohydrate metabolism occur unusual before, just have disorders of lipid metabolism, how with in various degree hyperlipemia.Main lipid metabolism Novel presentation is that blood triglyceride (TG) raises, highdensity lipoprotein-cholesterol (HDL-C) level reduces and the increasing of LDL-C (LDL-C).Therefore, control merely blood glucose and can not eliminate the macrovascular complications such as diabetics coronary heart disease fully, in the time of control blood glucose, must transfer the fat treatment.

Summary of the invention

The object of the present invention is to provide a kind of drug compound preparation for the treatment of diabetes and preparation method thereof; The present invention also provides the application of this drug compound preparation in the treatment diabetes.

The objective of the invention is to be achieved through the following technical solutions:

The crude drug of drug compound preparation of the present invention consists of:

Metformin 0.2-0.8 weight portion Rhizoma Atractylodis 1-5 weight portion Radix Scrophulariae 1-5 weight portion

Folium Mori 1-5 weight portion Folium Ginkgo 1-5 weight portion Rhizoma Alismatis 1-5 weight portion

Semen Trigonellae 1-5 weight portion.

The crude drug composition of drug compound preparation of the present invention is preferably:

Metformin 0.5 weight portion Rhizoma Atractylodis 3 weight portion Radix Scrophulariaes 3 weight portions

Folium Mori 3 weight portion Folium Ginkgos 3 weight portion Rhizoma Alismatis 3 weight portions

Semen Trigonellae 3 weight portions.

The crude drug composition of drug compound preparation of the present invention is preferably:

Metformin 0.3 weight portion Rhizoma Atractylodis 4 weight portion Radix Scrophulariaes 4 weight portions

Folium Mori 2 weight portion Folium Ginkgos 2 weight portion Rhizoma Alismatis 4 weight portions

Semen Trigonellae 4 weight portions.

The crude drug composition of drug compound preparation of the present invention is preferably:

Metformin 0.7 weight portion Rhizoma Atractylodis 2 weight portion Radix Scrophulariaes 2 weight portions

Folium Mori 4 weight portion Folium Ginkgos 4 weight portion Rhizoma Alismatis 2 weight portions

Semen Trigonellae 2 weight portions.

The above-mentioned raw materials medicine can be made into clinically acceptable dosage form, such as tablet, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

The present invention also provides the preparation method of this drug compound preparation, comprises the steps:

Step 1: get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 1-3 hour, decoct and extract 1-3 time, the each decoction 1-2 hour, each amount of water is 6-12 times, filters merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, dried cream powder is broken, and is for subsequent use;

Step 2: get Radix Scrophulariae, Rhizoma Alismatis, add 50-90% ethanol, soaked reflux, extract, 1-3 time 1-3 hour, each backflow 1-2 hour, each alcohol adding amount is 4-10 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, dried cream powder is broken, and is for subsequent use;

Step 3: get Folium Ginkgo, add 30-70% ethanol, soaked reflux, extract, 1-3 time 1-3 hour, each backflow 1-2 hour, each alcohol adding amount is 4-10 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05～1.08 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 5-20% (preferred 10%) ethanol elution with 2-5 times of bed volume amount, with 60-80% (preferred 70%) ethanol elution of 6-10 times of bed volume amount, collect ethanol elution, Recycled ethanol again, be evaporated to the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, dried cream powder is broken, and is for subsequent use;

Step 4: get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make clinical or pharmacy requires or the acceptable tablet of consumer, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

The preparation method of drug compound preparation of the present invention is preferably:

Step 1: get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 2 hours, decoct and extract 2 times, the each decoction 1.5 hours, amount of water is 10 times, 8 times, filters merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 2: get Radix Scrophulariae, Rhizoma Alismatis, add 70% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 3: get Folium Ginkgo, add 50% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filter, filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05～1.08 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 10% ethanol elution with 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, Recycled ethanol, be evaporated to the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 4: get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make clinical or pharmacy requires or the acceptable tablet of consumer, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

The preparation method of drug compound preparation of the present invention is preferably:

Step 1: get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 1.5 hours, decoct and extract 3 times, the each decoction 1 hour, each amount of water is 7 times, filters merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 2: get Radix Scrophulariae, Rhizoma Alismatis, add 80% ethanol, soaked reflux, extract, 3 times 1.5 hours, the each backflow 1 hour, each alcohol adding amount is 5 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 3: get Folium Ginkgo, add 60% ethanol, soaked reflux, extract, 3 times 1.5 hours, the each backflow 1 hour, each alcohol adding amount is 5 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05～1.08 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 10% ethanol elution with 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, Recycled ethanol, be evaporated to the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 4: get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make clinical or pharmacy requires or the acceptable tablet of consumer, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

The preparation method of drug compound preparation of the present invention is preferably:

Step 1: get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 2.5 hours, decoct and extract 1 time, decocted 2 hours, each amount of water is 11 times, filters merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 2: get Radix Scrophulariae, Rhizoma Alismatis, add 60% ethanol, soaked reflux, extract, 1 time 2.5 hours, the each backflow 2 hours, alcohol adding amount is 9 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 3: get Folium Ginkgo, add 40% ethanol, soaked reflux, extract, 1 time 2.5 hours, the each backflow 2 hours, alcohol adding amount is 9 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05～1.08 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 10% ethanol elution with 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, Recycled ethanol, be evaporated to the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 4: get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make clinical or pharmacy requires or the acceptable tablet of consumer, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

The present invention is directed to diabetes, take blood sugar lowering as main, select hypoglycemic essential drugs metformin, and closely around the guidance of theory of Chinese medical science, select the Chinese medicine boosting qi and nourishing yins such as Rhizoma Atractylodis, Radix Scrophulariae, Folium Mori, Rhizoma Alismatis, Folium Ginkgo, promoting the production of body fluid to quench thirst, the curative effect of enhancing blood sugar lowering.For the many facts with dyslipidemia of diabetes, it is turbid to select the QI invigorating such as Folium Mori, Rhizoma Alismatis, Folium Ginkgo, Semen Trigonellae to let out, and regulates blood fat simultaneously.The same usefulness of Chinese medicine and western medicine is based oneself upon primary disease, takes into account complication, and blood sugar lowering and blood fat reducing take into account, and Synergistic is scientific and reasonable.Side effect for the metformin of clinical appearance: the performances such as nausea,vomiting,diarrhea, select Rhizoma Atractylodis, Semen Trigonellae, Rhizoma Alismatis etc. with replenishing QI to invigorate the spleen, dehumidifying antidiarrheal, the untoward reaction that can effectively solve metformin.The same usefulness of above-mentioned Chinese medicine and western medicine does not have incompatibility, safe and reasonable.The present invention is according to diabetic disorders, develop a kind of metformin hydrochloride and Chinese medicine combine the treatment diabetes new compound preparation, give full play to Chinese medicine and western medicine advantage separately, both effectively blood sugar lowering, regulate blood fat, can alleviate complication again, also can alleviate the side effect of metformin, reach mutual supplement with each other's advantages, comprehensive treatment diabetes.

Following experimental example and embodiment all for the explanation but be not limited to the present invention.

Experimental example 1 metformin Chinese medicine hypoglycemic compound preparation is to the diabetic mice therapeutical effect laboratory report of model induced by alloxan

1.1 experiment material

1.1.1 the healthy kunming mice of laboratory animal, male and female half and half, body weight 22-24g raises in the zoopery of 18～22 ℃ of cleaning levels indoor.

1.1.2 experimental drug

Be subjected to reagent: metformin Chinese medicine hypoglycemic compound preparation (embodiment 1 preparation); Intending clinical people's consumption is 2.69g/60kgbw, i.e. 0.0448g/kg (people presses the 60kg weighing machine).

Positive control drug: glucophage (metformin hydrochloride) mice consumption is 0.333g/kg.Compound method: get tablet and add the deionized water grinding, be mixed with solution.

1.1.3 main agents

Glucose assays test kit, insulin radioimmunoassay test kit, alloxan.

1.2 experimental technique

1.2.1 healthy kunming mice is got in the foundation of model, male and female half and half, and body weight 22g-24g, adaptability are divided into normal control and model group at random by body weight after feeding for 1 week.Before setting up model, the equal fasting of Normal group and model group (can't help water) 24h, model group is with 200mgkg ^-1The dosage disposable celiac is injected 2% alloxan solution (before use, get an amount of alloxan, prepare with normal saline), the Normal group lumbar injection is got blood in eye socket with the dosage normal saline behind the 72h, leave standstill rear centrifugal (3000rpm, 10min) separation of serum is pressed the operation of glucose assays test kit description, measures at semi-automatic biochemical analyzer and detects fasting glucose (FBG), reject the too high or too low person of blood glucose, choose 50 FBG＞11mmolL ^-1Mice be that successful model is included experiment in.

1.2.2 the grouping administration keeps 10 mices of Normal group.Select 50 of standard compliant model group mices, according to fasting blood sugar, adopt randomized blocks to be divided into 5 groups, 10 every group.(1) Normal group: gavage is with the volume distilled water; (2) model control group: gavage is with the volume distilled water; (3) positive drug metformin hydrochloride matched group: gavage metformin hydrochloride solution, every day, dosage was 333mgkg ^-1(4) metformin Chinese medicine hypoglycemic compound preparation high dose group: gavage metformin Chinese medicine hypoglycemic compound preparation high dose solution, every day, dosage was 0.896gkg ^-1(be equivalent to people's quantity 20 times); (5) dosage group in the metformin Chinese medicine hypoglycemic compound preparation: dosage solution in the gavage metformin Chinese medicine hypoglycemic compound preparation, every day, dosage was 0.448gkg ^-1(be equivalent to people's quantity 10 times); (6) metformin Chinese medicine hypoglycemic compound preparation low dose group: gavage metformin Chinese medicine hypoglycemic compound preparation low dosage solution, every day, dosage was 0.224gkg ^-1(be equivalent to people's quantity 5 times).Each organizes gavage 1 time every day, and continuous 28 days, each medication volume calculated by every 10g body weight gavage 0.2mL.Respectively organize mice during the medication treatment and whenever daily raise with normal diet ad lib, drinking-water.

1.2.3 being prepared in during the medication treatment of blood sample, weekly 1 eye socket venous sinus blood sampling, the monitoring fasting blood sugar changes.Medication was treated the 28th day, and fasting (can't help water) 12h is behind the last administration 1h, pluck eyeball and get blood, inject a clean tube and leave standstill separation of serum, except FBG detected immediately, all the other blood serum samples were sub-packed in the 1.5mL cryopreservation tube ,-20 ℃ of cold storage of refrigerator relevant biochemistry to be checked, put and exempted from index.

1.2.4 observation index and detection method

Fasting plasma glucose: adopt glucose oxidase method.

Fasting insulin (fasting insulin, FINS) assay: adopt radio immunoassay.

Insulin Sensitivity Index (insulin sensitivity index, ISI): ISI=1/FBG/FINS.

1.2.5 statistical method

Experimental data is with mean ± standard deviation

The SPSS13.0 statistical software is adopted in expression, and relatively, significance level was take 0.05 and 0.01 as standard between the utilization one factor analysis of variance carried out respectively organizing.

1.3 experimental result

1.3.1 metformin Chinese medicine hypoglycemic compound preparation is on the impact of blood glucose in diabetic mice

Fasting glucose situation of change during the table 1 tissue of experimental diabetic mice medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Serum biochemistry is learned testing result and shown: before the medication treatment, the Normal group blood glucose value is 4.22 ± 0.84mmolL ^-1, the model group blood glucose value is 18.23 ± 5.23mmolL ^-1, model group and Normal group compare, and blood sugar level obviously raises (P＜0.01), and model group and each administration group blood sugar level there was no significant difference (P＞0.05).Medication treated for the 2nd week, and metformin group, metformin Chinese medicine hypoglycemic compound preparation high dose group blood sugar level are than model group obviously descend (P＜0.05); Medication treated for the 3rd week, and metformin group, metformin Chinese medicine hypoglycemic compound preparation high dose group blood sugar level are than model group obviously descend (P＜0.05); Medication treated for the 4th week, and metformin group, metformin Chinese medicine hypoglycemic compound preparation are high, middle dosage group blood sugar level is than model group obviously descend (P＜0.01 or P＜0.05).(seeing Table 1)

1.3.2 metformin Chinese medicine hypoglycemic compound preparation is on the impact of diabetic mice serum insulin content

Radioimmunity detects the result and shows: before the medication treatment, Normal group mice Diagnostic Value of Fasting Serum insulin content is 14.53 ± 4.22 μ IUml after the modeling ^-1, model group is 28.91 ± 5.14 μ IUml ^-1, model group compared with normal matched group Diagnostic Value of Fasting Serum insulin content obviously raise (P＜0.01).Medication treated for 2 weeks, and metformin group Diagnostic Value of Fasting Serum insulin content obviously reduces (P＜0.05) than model group.Medication treated for 3 weeks, and metformin Chinese medicine hypoglycemic compound preparation high dose group, metformin group Diagnostic Value of Fasting Serum insulin content obviously reduce (P＜0.05) than model group.Medication treated for 4 weeks, and metformin Chinese medicine hypoglycemic compound preparation height, middle dosage group, metformin group Diagnostic Value of Fasting Serum insulin content obviously reduce (P＜0.05 or P＜0.01) than model group.(seeing Table 2)

Serum insulin content situation of change during the table 2 tissue of experimental diabetic mice medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

1.3.3 metformin Chinese medicine hypoglycemic compound preparation is on the impact of diabetic mice insulin sensitivity index

Insulin sensitivity index situation of change during the table 3 tissue of experimental diabetic mice medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Before medication is treated after the modeling, Normal group mouse islets element Sensitivity Index is 0.0150 ± 0.0027, the model group insulin sensitivity index is 0.0020 ± 0.0007, and model group and Normal group compare, and insulin sensitivity index obviously reduces (P＜0.01).Medication treated for 2 weeks, and metformin Chinese medicine hypoglycemic compound preparation high dose group, metformin group insulin sensitivity index are than model group obviously raise (P＜0.05).Medication treated for 3 weeks, and metformin Chinese medicine hypoglycemic compound preparation height, middle dosage group, metformin group insulin sensitivity index are than model group obviously raise (P＜0.05 or P＜0.01).Medication treated for 4 weeks, and the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation, metformin group insulin sensitivity index are than model group obviously raise (P＜0.01).(seeing Table 3)

1.4 conclusion:

Metformin Chinese medicine hypoglycemic compound preparation can obviously reduce blood glucose in diabetic mice, reduce Diagnostic Value of Fasting Serum insulin content, rising insulin sensitivity index.

Has hypoglycemic function by this description of test " metformin Chinese medicine hypoglycemic compound preparation ".This experiment tested material is metformin Chinese medicine hypoglycemic compound preparation, and the consumption per day of metformin is compared obvious reduction with the metformin matched group in the tested material.But the pharmacological results shows that the height of tested material, middle dosage group are compared with the metformin matched group has suitable hypoglycemic activity.Therefore, by reducing consumption per day and the reasonable compatibility Chinese medicine of metformin, not only reach hypoglycemic activity, and can alleviate to a certain extent the untoward reaction that simple use high dose metformin produces.

Experimental example 2 metformin Chinese medicine hypoglycemic compound preparations are on the laboratory report that affects of normal glucose tolerance in mice

2.1 experiment material

2.1.1 the healthy ICR mice of laboratory animal, male and female half and half, body weight 18-20g raises in the zoopery of 18～22 ℃ of cleaning levels indoor.

2.1.2 experimental drug

Be subjected to reagent: metformin Chinese medicine hypoglycemic compound preparation (embodiment 1 preparation); Intending clinical people's consumption is 2.69g/60kgbw, i.e. 0.0448g/kg (people presses the 60kg weighing machine).

Positive control drug: glucophage (metformin hydrochloride): the mice consumption is 0.333g/kg.Compound method: get tablet and add the deionized water grinding, be mixed with solution.

2.1.3 main agents

Glucose assays test kit, glucose.

2.2 experimental technique

2.2.1 grouping administration: normal ICR mice, after adaptability raised for 1 week, according to the body weight value, adopt randomized blocks to be divided into 5 groups.(1) blank group: gavage is with the volume distilled water; (2) positive drug metformin hydrochloride matched group: gavage metformin hydrochloride solution, every day, dosage was 300mgkg ^-1(3) metformin Chinese medicine hypoglycemic compound preparation high dose group: gavage metformin Chinese medicine hypoglycemic compound preparation high dose solution, every day, dosage was 0.896gkg ^-1(be equivalent to people's quantity 20 times); (4) dosage group in the metformin Chinese medicine hypoglycemic compound preparation: dosage solution in the gavage metformin Chinese medicine hypoglycemic compound preparation, every day, dosage was 0.448gkg ^-1(be equivalent to people's quantity 10 times); (5) metformin Chinese medicine hypoglycemic compound preparation low dose group: gavage metformin Chinese medicine hypoglycemic compound preparation low dosage solution, every day, dosage was 0.224gkg ^-1(be equivalent to people's quantity 5 times).Each organizes gavage 1 time every day, and continuous 8 days, each medication volume calculated by every 10g body weight gavage 0.2mL.Respectively organize mice during the medication and whenever daily raise with normal diet ad lib, drinking-water.

2.2.2 experimental procedure

Fasting (can't help water) is 8 hours before administration in the 8th day, and eye socket is got blood, and biochemical instruments is measured fasting blood sugar (0h), gastric infusion again, and Normal group is to the equivalent distilled water.Gavage glucose (2.5g/kg) behind the 1h, eye socket is got blood, and biochemical instruments is measured to 0.5,1.0,2.0 blood glucose value after the sugar.

2.3 statistical method: experimental data is with mean ± standard deviation

The SPSS13.0 statistical software is adopted in expression, and relatively, significance level was take 0.05 and 0.01 as standard between the utilization one factor analysis of variance carried out respectively organizing.

2.4 experimental result

Table 4 metformin Chinese medicine hypoglycemic compound preparation is on the impact of normal glucose tolerance in mice

Annotate: compare with normal group ^*P＜0.05 ^*P＜0.01

After giving glucose, the mouse blood sugar level obviously raises, 0.5h the time reach peak, metformin and metformin Chinese medicine hypoglycemic compound preparation are high, middle dosage group can significantly reduce mice and give 0.5h behind the glucose, 1h blood glucose value (P＜0.05 or P＜0.01), blood sugar level is passed in time gradually and is fallen after rise, and after 2 hours, each group all reaches normal level.(seeing Table 4)

2.5 conclusion:

Metformin Chinese medicine hypoglycemic compound preparation can obviously be accelerated the falling speed of blood sugar level.This experiment tested material is metformin Chinese medicine hypoglycemic compound preparation, and the consumption per day of metformin is compared obvious reduction with the metformin matched group in the tested material.But the pharmacological results shows that the height of tested material, middle dosage group are compared with the metformin matched group has the effect that suitable quickening blood sugar level falls speed after rise.Therefore, by reducing consumption per day and the reasonable compatibility Chinese medicine of metformin, not only reach hypoglycemic activity, and can alleviate to a certain extent the untoward reaction that simple use high dose metformin produces.

Experimental example 3 metformin Chinese medicine hypoglycemic compound preparations merge the therapeutical effect laboratory report of hyperlipidemia rats to artificial diabetes

3.1 test material

3.1.1 animal

The Wistar male rat, secondary, body weight 180-200g.

3.1.2 medicine

Be subjected to reagent: metformin Chinese medicine hypoglycemic compound preparation (embodiment preparation); Intending clinical people's consumption is 2.69g/60kgbw, i.e. 0.0448g/kg (people presses the 60kg weighing machine).

Positive control drug: glucophage (metformin hydrochloride): the rat consumption is 0.267g/kg.Compound method: get tablet and add the deionized water grinding, be mixed with solution.

XUEZHIKANG JIAONANG, rat consumption are 0.160g/kg.Compound method: take out capsule 's content, be mixed with solution with deionized water.

3.1.3 experiment reagent blood sugar detection test kit, TG mensuration test kit, TC mensuration test kit, LDL-C measure test kit, HDL-C measures test kit; The glucose assays test kit; Streptozotocin; The insulin radioimmunological kit.

3.2 experimental technique

3.2.1 set up the diabetes hyperlipaemia animal model.Select male Wistar rat, body weight 180～200g, normally feed a week after, be divided into Normal group and model group by the body weight randomized blocks, Normal group feed normal diet, model group feed high glucose and high fat feedstuff, continuous 8 weeks.After 8 weeks, fasting (can't help water) 12h, eye socket get blood and survey blood glucose, and model group is with 30mgkg ^-1Dosage disposable celiac injection 2%STZ solution, the Normal group lumbar injection detects fasting glucose, blood fat, with fasting glucose＞11mmolL with dosage citric acid-sodium citrate buffer behind the 72h ^-1Be main, double see raise cholesterol (TC), serum triglycerides (TG) content to have the rat of significant difference with Normal group be that successful model is included experiment in.

3.2.2 grouping and administration: keep 10 rats of Normal group.Select 48 of standard compliant model group rats, according to fasting blood sugar, adopt randomized blocks to be divided into 6 groups, 8 every group.(1) blank group: gavage is with the volume distilled water; (2) model control group: gavage is with the volume distilled water; (3) positive drug metformin hydrochloride matched group: gavage metformin hydrochloride solution, every day, dosage was 0.267gkg ^-1(4) positive drug Xuezhikang matched group: gavage Xuezhikang solution, every day, dosage was 0.160gkg ^-1(5) metformin Chinese medicine hypoglycemic compound preparation high dose group: gavage metformin Chinese medicine hypoglycemic compound preparation high dose solution, every day, dosage was 0.716gkg ^-1(be equivalent to people's quantity 16 times); (6) dosage group in the metformin Chinese medicine hypoglycemic compound preparation: dosage solution in the gavage metformin Chinese medicine hypoglycemic compound preparation, every day, dosage was 0.358gkg ^-1(be equivalent to people's quantity 8 times); (7) metformin Chinese medicine hypoglycemic compound preparation low dose group: gavage metformin Chinese medicine hypoglycemic compound preparation low dosage solution, every day, dosage was 0.179gkg ^-1(be equivalent to people's quantity 4 times).In continuous 4 weeks, respectively organize rat during the medication treatment and whenever daily raise with normal diet ad lib, drinking-water.Count weekly body weight and food-intake.

3.2.3 the preparation of blood sample and urine specimen.Treated for the 2nd week in medication, in 4 weeks, ether is slightly anaesthetized, the blood sampling of eye socket venous sinus, and Monitoring Blood Glucose and four items of blood lipid tests (TC, TG, LDL-C, HDL-C) change.Medication treated for the 5th week, and fasting (can't help water) 8 hours, last administration were carried out the carbohydrate tolerance experiment after 1 hour.Medication treated for the 6th week, and fasting (can't help water) 8 hours, last administration are after 1 hour, and 3.5% chloral hydrate intraperitoneal injection of anesthesia extracts the intravesical urine, injects a clean tube, and is for subsequent use.The ventral aorta blood sampling is injected a clean tube and is left standstill, and 4 ℃, 3500rmin ^-1, centrifugal 10min, separation of serum, except FBG (fasting glucose) detected immediately, all the other serum, sample were sub-packed in the 1.5mL cryopreservation tube ,-20 ℃ of cold storage of refrigerator relevant biochemistry to be checked, put and exempted from index.

3.2.4 observation index and detection method

3.2.4.1 the observation of growth of animal and the situation of ingesting: experimental session is observed animal spirit, activity, hair color, feed, drinking-water and urine quantitative change, and records weekly the weight of animals, food-intake, amount of drinking water once.

3.2.4.2 fasting plasma glucose: adopt glucose oxidase method.

3.2.4.3 fasting insulin (fasting insulin, FINS) assay: adopt radio immunoassay.

3.2.4.4 insulin sensitivity (sensitivity): ISI=1/FBG/FINS

3.2.4.5 cholesterol (TC) assay: adopt enzymic colorimetric.

3.2.4.6 triglyceride (TG) assay: adopt enzymic colorimetric.

3.2.4.7 low density cholesterol lipoprotein (LDL-C) assay: adopt polyvinyel sulfate.

3.2.4.8 HDL-C lipoprotein (HDL-C) assay: adopt phosphotungstic acid-magnesium precipitate method.

3.2.5 statistical method

Experimental data is with mean ± standard deviation

The SPSS13.0 statistical software is adopted in expression, and relatively, significance level was take 0.05 and 0.01 as standard between the utilization one factor analysis of variance carried out respectively organizing.

3.3 experimental result:

3.3.1 metformin Chinese medicine hypoglycemic compound preparation merges the impact of hyperlipidemia rats growth and the situation of ingesting on artificial diabetes

3.3.1.1 ordinary circumstance: the rats in normal control group mental status is good, is quick on the draw, and moves freely, and fur is glossy.During 2 months, the figure is fat at high glucose and high fat feedstuff feed for the model group rat, and is drowsiness few moving, behind the disposable celiac injection 2%STZ, food-intake, amount of drinking water, urine amount increase, and health is become thin gradually, lethargy, bradykinesia, slow movement, hair is perpendicular matt, the curling oneself up back of a bow.The high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation and metformin group, XUEZHIKANG JIAONANG group rat also have similar performance, but degree is lighter.

3.3.1.2 body weight change situation

Body weight change situation during the modeling of table 5 artificial diabetes merging hyperlipidemia rats

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

During the modeling, in 8 weeks of normal rats normal diet feed, body weight steadily increases to 449.24 ± 25.72g by 209.15 ± 7.15g.In model group rat high glucose and high fat feedstuff 8 weeks of feed, body weight increases to 477.27 ± 32.32g by 206.42 ± 6.29g, is significantly higher than Normal group (P＜0.05).Behind the disposable celiac injection 2%STZ 72h, body weight is reduced to rapidly 436.52 ± 28.46g by 477.27 ± 32.32g, significantly is lower than Normal group (P＜0.05).(seeing Table 5)

Body weight change situation during the table 6 artificial diabetes merging hyperlipidemia rats medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

During the medication treatment, the rats in normal control group body weight increases to 499.65 ± 34.88g by 469.58 ± 22.69g.The model group rat body weight is reduced to 364.22 ± 31.00g by 431.29 ± 30.55g, is starkly lower than Normal group (P＜0.01).The high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation, metformin control rats body weight and model group relatively have significant difference (P＜0.05 or P＜0.01).(seeing Table 6)

3.3.1.3 food-intake situation of change

Food-intake situation of change during the modeling of table 7 artificial diabetes merging hyperlipidemia rats

During the modeling, rats in normal control group feed normal diet, on average every day, every 100g body weight food-intake was between 8.92～9.51g.Model group rat feeding high glucose and high fat feedstuff, owing to be not suitable with new feedstuff, feed front average every day in 3 weeks of every 100g body weight food-intake is between 8.95～9.24g, 4～8 weeks then food-intake increase gradually, on average every day, every 100g body weight food-intake was between 9.29～9.59g, behind the disposable celiac injection 2%STZ 72h, on average every day, every 100g body weight food-intake increased to 12.61g by 9.58g.(seeing Table 7)

Food-intake situation of change during the table 8 artificial diabetes merging hyperlipidemia rats medication treatment

During the medication treatment, each organizes the equal feed normal diet of rat, and rats in normal control group average every day of every 100g body weight food-intake is between 9.11～9.67g.Model group rat average every day of every 100g body weight food-intake and shows a rising trend with the prolongation for the treatment of cycle between 12.35～16.25g.Through 4 week treatments, the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation, metformin group, average every day of Xuezhikang group rat, every 100g body weight food-intake all had minimizing trend than model group.(seeing Table 8)

3.3.1.4 amount of drinking water situation of change

Amount of drinking water situation of change during the modeling of table 9 artificial diabetes merging hyperlipidemia rats:

During the modeling, rats in normal control group average every day of every 100g body weight amount of drinking water is between 18.22～21.29ml.Model group rat average every day of every 100g body weight amount of drinking water is between 18.48～20.36ml, and behind the disposable celiac injection 2%STZ72h, on average every day, every 100g body weight amount of drinking water increased to 27.35ml.(seeing Table 9)

Amount of drinking water situation of change during the table 10 artificial diabetes merging hyperlipidemia rats medication treatment

During the medication treatment, rats in normal control group average every day of every 100g body weight amount of drinking water is between 18.44～18.88ml.Model group rat average every day of every 100g body weight amount of drinking water increases to 60.32ml by 28.25ml.Through the treatment of 4 weeks, the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation and metformin, average every day of Xuezhikang group rat, every 100g body weight amount of drinking water was about 41.65ml, 33.53ml, 32.89ml, 35.87ml, 44.73ml, all than model group minimizing trend was arranged.(seeing Table 10)

3.3.1.5 urine quantitative change situation

Rats in normal control group is during modeling and medication treatment, and the urine amount is without significant change.Behind the model group rat disposable celiac injection 2%STZ, observe urine amount showed increased from the bedding and padding degree of soaking.During the medication treatment, the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation and metformin group, it is light than model group that bedding and padding soak degree, reflects that indirectly its urine amount reduces than model group.

3.3.2 metformin Chinese medicine hypoglycemic compound preparation merges the impact of hyperlipidemia rats blood glucose on artificial diabetes

Fasting glucose situation of change during the table 11 artificial diabetes merging hyperlipidemia rats medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Serum biochemistry is learned testing result and shown: medication treated for the 2nd week, and dosage group blood sugar level is than model group obviously descend (P＜0.05 or P＜0.01) in metformin group, the metformin Chinese medicine hypoglycemic compound preparation; Medication treated for the 3rd week, and metformin group, Xuezhikang matched group, metformin Chinese medicine hypoglycemic compound preparation are high, middle dosage group blood sugar level is than model group obviously descend (P＜0.05 or P＜0.01); Medication treated for the 4th week, and metformin group, the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation blood sugar level are than model group obviously descend (P＜0.05 or P＜0.01).(seeing Table 11)

3.3.3 metformin Chinese medicine hypoglycemic compound preparation merges the impact of hyperlipidemia rats serum insulin content on artificial diabetes

Serum insulin content situation of change during the table 12 artificial diabetes merging hyperlipidemia rats medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Radioimmunity detects the result and shows: before the medication treatment, rats in normal control group Diagnostic Value of Fasting Serum insulin content is 13.15 ± 2.50 μ IUml after the modeling ^-1, model group is 22.57 ± 3.73 μ IUml ^-1, model group compared with normal matched group Diagnostic Value of Fasting Serum insulin content obviously raise (P＜0.01).Medication treated for 3 weeks, and metformin Chinese medicine hypoglycemic compound preparation height, middle dosage group, metformin group Diagnostic Value of Fasting Serum insulin content obviously reduce (P＜0.05 or P＜0.01) than model group.Medication treated for 4 weeks, and metformin Chinese medicine hypoglycemic compound preparation height, middle dosage group, metformin group Diagnostic Value of Fasting Serum insulin content obviously reduce (P＜0.05 or P＜0.01) than model group.(seeing Table 12)

3.3.4 metformin Chinese medicine hypoglycemic compound preparation merges the impact of hyperlipidemia rats insulin sensitivity index on artificial diabetes

Insulin sensitivity index situation of change during the table 13 artificial diabetes merging hyperlipidemia rats medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Before medication is treated after the modeling, the rats in normal control group insulin sensitivity index is 0.0136 ± 0.0046, the model group insulin sensitivity index is 0.0028 ± 0.0006, and model group and Normal group compare, and insulin sensitivity index obviously reduces (P＜0.01).Medication treated for 2 weeks, and metformin Chinese medicine hypoglycemic compound preparation height, middle dosage group, metformin group insulin sensitivity index are than model group obviously raise (P＜0.05).Medication treated for 3 weeks, and metformin Chinese medicine hypoglycemic compound preparation height, middle dosage group, metformin group, Xuezhikang matched group insulin sensitivity index are than model group obviously raise (P＜0.05 or P＜0.01).Medication treated for 4 weeks, and the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation, metformin group, Xuezhikang matched group insulin sensitivity index are than model group obviously raise (P＜0.05 or P＜0.01).(seeing Table 13)

3.3.5 metformin Chinese medicine hypoglycemic compound preparation merges the impact of the total TC content of hyperlipidemia rats serum on artificial diabetes

TC situation of change during the table 14 artificial diabetes merging hyperlipidemia rats medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Serum biochemistry is learned testing result and shown: 2-4 week is treated in medication, and metformin group, Xuezhikang matched group, the total TC content of the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation serum are all than model group obviously descend (P＜0.05 or P＜0.01).(seeing Table 14)

3.3.6 metformin Chinese medicine hypoglycemic compound preparation merges the impact of hyperlipidemia rats serum TG content on artificial diabetes

TG situation of change during the table 15 artificial diabetes merging hyperlipidemia rats medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Serum biochemistry is learned testing result and shown: treat 2-4 week, metformin group, Xuezhikang matched group, the total TG content of the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation serum are all than model group obviously descend (P＜0.05 or P＜0.01).(seeing Table 15)

3.3.7 metformin Chinese medicine hypoglycemic compound preparation merges the impact of hyperlipidemia rats serum LDL-C content on artificial diabetes

LDL-C situation of change during the table 16 artificial diabetes merging hyperlipidemia rats medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Serum biochemistry is learned testing result and shown: treat 2-4 week, metformin group, Xuezhikang matched group, the total LDL-C content of the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation serum are all than model group obviously descend (P＜0.05 or P＜0.01).(seeing Table 16)

3.3.8 metformin Chinese medicine hypoglycemic compound preparation merges the impact of hyperlipidemia rats Serum HDL-C content on artificial diabetes

HDL-C situation of change during the table 17 artificial diabetes merging hyperlipidemia rats medication treatment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Serum biochemistry is learned testing result and is shown: treated for 2 weeks, in metformin group, the metformin Chinese medicine hypoglycemic compound preparation, the total HDL-C content of low dose group serum is all than model group obviously raise (P＜0.01).In treatment 3-4 week, metformin group, Xuezhikang matched group, the total HDL-C content of the high, medium and low dosage group of metformin Chinese medicine hypoglycemic compound preparation serum are all than model group obviously raise (P＜0.01).(seeing Table 17)

3.4 conclusion:

The resultant effect of metformin Chinese medicine hypoglycemic compound preparation hypoglycemic is better.This experiment tested material is metformin Chinese medicine hypoglycemic compound preparation, and the consumption per day of metformin is compared obvious reduction with the metformin matched group in the tested material.But the pharmacological results shows, metformin Chinese medicine hypoglycemic compound preparation blood sugar lowering, the effect of regulating blood fat and metformin matched group, Xuezhikang matched group are suitable, therefore, by reducing consumption per day and the reasonable compatibility Chinese medicine of metformin, not only reach the effect of hypoglycemic, and can alleviate to a certain extent the untoward reaction that simple use high dose metformin produces.

The specific embodiment

Embodiment 1: the preparation of tablet of the present invention

Metformin 0.5g Rhizoma Atractylodis 3g Radix Scrophulariae 3g Folium Mori 3g Folium Ginkgo 3g Rhizoma Alismatis 3g Semen Trigonellae 3g;

Get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 2 hours, decoct and extract 2 times, decocted 1.5 hours at every turn, amount of water is 10 times, 8 times, filter, merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Radix Scrophulariae, Rhizoma Alismatis, add 70% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Folium Ginkgo, add 50% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filter, filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05～1.08 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 10% ethanol elution with 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, Recycled ethanol, be evaporated to the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make tablet.

Embodiment 2: the preparation of capsule of the present invention

Metformin 0.3g Rhizoma Atractylodis 4g Radix Scrophulariae 4g Folium Mori 2g Folium Ginkgo 2g

Rhizoma Alismatis 4g Semen Trigonellae 4g;

Get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 1.5 hours, decoct and extract 3 times, decocted 1 hour at every turn, each amount of water is 7 times, filter, merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Radix Scrophulariae, Rhizoma Alismatis, add 80% ethanol, soaked reflux, extract, 3 times 1.5 hours, the each backflow 1 hour, each alcohol adding amount is 5 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Folium Ginkgo, add 60% ethanol, soaked reflux, extract, 3 times 1.5 hours, the each backflow 1 hour, each alcohol adding amount is 5 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05～1.08 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 5% ethanol elution with 2 times of bed volume amounts, use again 60% ethanol elution of 8 times of bed volume amounts, collect 60% ethanol elution, Recycled ethanol, be evaporated to the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make capsule.

Embodiment 3: the preparation of granule of the present invention

Metformin 0.7g Rhizoma Atractylodis 2g Radix Scrophulariae 2g Folium Mori 4g Folium Ginkgo 4g

Rhizoma Alismatis 2g Semen Trigonellae 2g;

Get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 2.5 hours, decoct and extract 1 time, decocted 2 hours, amount of water is 11 times at every turn, filter, merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Radix Scrophulariae, Rhizoma Alismatis, add 60% ethanol, soaked reflux, extract, 1 time 2.5 hours, the each backflow 2 hours, alcohol adding amount is 9 times, filters, filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, and broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Folium Ginkgo, add 40% ethanol, soaked reflux, extract, 1 time 2.5 hours, the each backflow 2 hours, alcohol adding amount is 9 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05～1.08 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 20% ethanol elution with 5 times of bed volume amounts, use again 80% ethanol elution of 8 times of bed volume amounts, collect 80% ethanol elution, Recycled ethanol, be evaporated to the thick paste of relative density 1.20～1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, the granulation agent.

Embodiment 4: the preparation of unguentum of the present invention

Metformin 0.5g Rhizoma Atractylodis 3g Radix Scrophulariae 3g Folium Mori 3g Folium Ginkgo 3g Rhizoma Alismatis 3g Semen Trigonellae 3g;

Get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 2 hours, decoct and extract 2 times, decocted 1.5 hours at every turn, amount of water is 10 times, 8 times, filter, merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Radix Scrophulariae, Rhizoma Alismatis, add 70% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filters, filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20 (60 ℃ of surveys), drying under reduced pressure, and broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Folium Ginkgo, add 50% ethanol, soaked 2 hours, reflux, extract, 2 times, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filter, filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05 (60 ℃ of surveys), and cold preservation is filtered, filtrate is passed through macroporous adsorbent resin, with 10% ethanol elution of 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, collect ethanol elution, Recycled ethanol is evaporated to the thick paste of relative density 1.20 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make unguentum.

Embodiment 5: the preparation of slow releasing preparation of the present invention

Metformin 0.3g Rhizoma Atractylodis 4g Radix Scrophulariae 4g Folium Mori 2g Folium Ginkgo 2g

Rhizoma Alismatis 4g Semen Trigonellae 4g;

Get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 3 hours, decoct and extract 3 times, decocted 2 hours at every turn, amount of water is 10 times, 8 times, filter, merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Radix Scrophulariae, Rhizoma Alismatis, add 70% ethanol, soaked reflux, extract, 3 times 3 hours, the each backflow 2 hours, alcohol adding amount is 8 times, 6 times, filters, filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20 (60 ℃ of surveys), drying under reduced pressure, and broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Folium Ginkgo, add 50% ethanol, soaked reflux, extract, 3 times 3 hours, the each backflow 2 hours, alcohol adding amount is 8 times, 6 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 10% ethanol elution with 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, Recycled ethanol, be evaporated to the thick paste of relative density 1.20 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use.

Get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make slow releasing preparation.

Embodiment 6: the preparation of quick releasing formulation of the present invention

Metformin 0.7g Rhizoma Atractylodis 2g Radix Scrophulariae 2g Folium Mori 4g Folium Ginkgo 4g

Rhizoma Alismatis 2g Semen Trigonellae 2g;

Get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 2 hours, decoct and extract 2 times, decocted 1.5 hours at every turn, amount of water is 10 times, 8 times, filter, merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.20 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Radix Scrophulariae, Rhizoma Alismatis, add 70% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filters, filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.20 (60 ℃ of surveys), drying under reduced pressure, and broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Folium Ginkgo, add 50% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.05 (60 ℃ of surveys), cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 5% ethanol elution with 2 times of bed volume amounts, use again 60% ethanol elution of 10 times of bed volume amounts, collect 60% ethanol elution, Recycled ethanol, be evaporated to the thick paste of relative density 1.20 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make quick releasing formulation.

Embodiment 7: the preparation of oral liquid of the present invention

Metformin 0.5g Rhizoma Atractylodis 3g Radix Scrophulariae 3g Folium Mori 3g Folium Ginkgo 3g Rhizoma Alismatis 3g Semen Trigonellae 3g;

Get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 1 hour, decoct and extract 1 time, decocted 1 hour at every turn, amount of water is 10 times, 8 times, filter, merging filtrate, filtrate decompression is concentrated into the thick paste of relative density 1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Radix Scrophulariae, Rhizoma Alismatis, add 70% ethanol, soaked reflux, extract, 1 time 1 hour, the each backflow 1 hour, alcohol adding amount is 8 times, 6 times, filters, filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 1.25 (60 ℃ of surveys), drying under reduced pressure, and broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Get Folium Ginkgo, add 50% ethanol, soaked 1 hour, reflux, extract, 1 time, the each backflow 1 hour, alcohol adding amount is 8 times, 6 times, filter, filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 1.08 (60 ℃ of surveys), and cold preservation is filtered, filtrate is passed through macroporous adsorbent resin, with 20% ethanol elution of 5 times of bed volume amounts, use again 80% ethanol elution of 6 times of bed volume amounts, collect 80% ethanol elution, collect ethanol elution, Recycled ethanol is evaporated to the thick paste of relative density 1.25 (60 ℃ of surveys), drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use.

Get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make oral liquid.

Claims (10)

1. drug compound preparation for the treatment of diabetes is characterized in that the crude drug of said preparation consists of:

Metformin 0.2-0.8 weight portion Rhizoma Atractylodis 1-5 weight portion Radix Scrophulariae 1-5 weight portion

Folium Mori 1-5 weight portion Folium Ginkgo 1-5 weight portion Rhizoma Alismatis 1-5 weight portion

Semen Trigonellae 1-5 weight portion.

2. drug compound preparation as claimed in claim 1 is characterized in that the crude drug of said preparation consists of:

Metformin 0.5 weight portion Rhizoma Atractylodis 3 weight portion Radix Scrophulariaes 3 weight portions

Folium Mori 3 weight portion Folium Ginkgos 3 weight portion Rhizoma Alismatis 3 weight portions

Semen Trigonellae 3 weight portions.

3. drug compound preparation as claimed in claim 1 is characterized in that the crude drug of said preparation consists of:

Metformin 0.3 weight portion Rhizoma Atractylodis 4 weight portion Radix Scrophulariaes 4 weight portions

Folium Mori 2 weight portion Folium Ginkgos 2 weight portion Rhizoma Alismatis 4 weight portions

Semen Trigonellae 4 weight portions.

4. drug compound preparation as claimed in claim 1 is characterized in that the crude drug of said preparation consists of:

Metformin 0.7 weight portion Rhizoma Atractylodis 2 weight portion Radix Scrophulariaes 2 weight portions

Folium Mori 4 weight portion Folium Ginkgos 4 weight portion Rhizoma Alismatis 2 weight portions

Semen Trigonellae 2 weight portions.

5. the preparation method of drug compound preparation is characterized in that the method comprises the steps: as described in arbitrary such as claim 1-4

Step 1: get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 1-3 hour, decoct and extract 1-3 time, decocted 1-2 hour at every turn, each amount of water is 6-12 times, filter, merging filtrate, filtrate decompression is concentrated into 60 ℃ of relative densities and surveys 1.20～1.25 thick paste, drying under reduced pressure, dried cream powder is broken, and is for subsequent use;

Step 2: get Radix Scrophulariae, Rhizoma Alismatis, add 50-90% ethanol, soaked reflux, extract, 1-3 time 1-3 hour, each backflow 1-2 hour, each alcohol adding amount is 4-10 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the thick paste that relative density is 60 ℃ of surveys 1.20～1.25, drying under reduced pressure, dried cream powder is broken, and is for subsequent use;

Step 3: get Folium Ginkgo, add 30-70% ethanol, soaked reflux, extract, 1-3 time 1-3 hour, each backflow 1-2 hour, each alcohol adding amount is 4-10 times, filters, and filtrate merges, Recycled ethanol also is concentrated into the concentrated solution that relative density is 60 ℃ of surveys 1.05～1.08, cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 5-20% ethanol elution with 2-5 times of bed volume amount, with the 60-80% ethanol elution of 6-10 times of bed volume amount, collect ethanol elution, Recycled ethanol again, be evaporated to 60 ℃ of thick pastes of surveying 1.20-1.25 of relative density, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 4: get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make clinical or pharmacy requires or the acceptable tablet of consumer, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

6. preparation method as claimed in claim 5 is characterized in that the method comprises the steps:

Step 1: get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 2 hours, decoct and extract 2 times, decocted 1.5 hours at every turn, amount of water is 10 times, 8 times, filter merging filtrate, the thick paste of relative density 1.20～1.25 when filtrate decompression is concentrated into 60 ℃, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 2: get Radix Scrophulariae, Rhizoma Alismatis, add 70% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filters, and filtrate merges, Recycled ethanol and when being concentrated into 60 ℃ relative density be 1.20～1.25 thick paste, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 3: get Folium Ginkgo, add 50% ethanol, soaked reflux, extract, 2 times 2 hours, the each backflow 1.5 hours, alcohol adding amount is 8 times, 6 times, filters, and filtrate merges, Recycled ethanol and when being concentrated into 60 ℃ relative density be 1.05～1.08 concentrated solution, cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 10% ethanol elution with 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, Recycled ethanol, the thick paste of relative density 1.20～1.25 when being evaporated to 60 ℃, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 4: get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make clinical or pharmacy requires or the acceptable tablet of consumer, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

7. preparation method as claimed in claim 5 is characterized in that the method comprises the steps:

Step 1: get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 1.5 hours, decoct and extract 3 times, decocted 1 hour at every turn, each amount of water is 7 times, filter merging filtrate, the thick paste of relative density 1.20～1.25 when filtrate decompression is concentrated into 60 ℃, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 2: get Radix Scrophulariae, Rhizoma Alismatis, add 80% ethanol, soaked reflux, extract, 3 times 1.5 hours, the each backflow 1 hour, each alcohol adding amount is 5 times, filters, and filtrate merges, Recycled ethanol and when being concentrated into 60 ℃ relative density be 1.20～1.25 thick paste, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 3: get Folium Ginkgo, add 60% ethanol, soaked reflux, extract, 3 times 1.5 hours, the each backflow 1 hour, each alcohol adding amount is 5 times, filters, and filtrate merges, Recycled ethanol and when being concentrated into 60 ℃ relative density be 1.05～1.08 concentrated solution, cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 10% ethanol elution with 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, Recycled ethanol, the thick paste of relative density 1.20～1.25 when being evaporated to 60 ℃, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 4: get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make clinical or pharmacy requires or the acceptable tablet of consumer, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

8. preparation method as claimed in claim 5 is characterized in that the method comprises the steps:

Step 1: get Rhizoma Atractylodis, Folium Mori, Semen Trigonellae and soaked 2.5 hours, decoct and extract 1 time, decocted 2 hours, amount of water is 11 times at every turn, filter merging filtrate, the thick paste of relative density 1.20～1.25 when filtrate decompression is concentrated into 60 ℃, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 2: get Radix Scrophulariae, Rhizoma Alismatis, add 60% ethanol, soaked reflux, extract, 1 time 2.5 hours, the each backflow 2 hours, alcohol adding amount is 9 times, filters, filtrate merges, Recycled ethanol and when being concentrated into 60 ℃ relative density be 1.20～1.25 thick paste, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 3: get Folium Ginkgo, add 40% ethanol, soaked reflux, extract, 1 time 2.5 hours, the each backflow 2 hours, alcohol adding amount is 9 times, filters, and filtrate merges, Recycled ethanol and when being concentrated into 60 ℃ relative density be 1.05～1.08 concentrated solution, cold preservation is filtered, and filtrate is passed through macroporous adsorbent resin, 10% ethanol elution with 4 times of bed volume amounts, use again 70% ethanol elution of 8 times of bed volume amounts, collect 70% ethanol elution, Recycled ethanol, the thick paste of relative density 1.20～1.25 when being evaporated to 60 ℃, drying under reduced pressure, broken mistake 80 mesh sieves of dried cream powder, for subsequent use;

Step 4: get metformin, evenly mixed with the dried cream powder of above-mentioned steps 1-3, according to common process, make clinical or pharmacy requires or the acceptable tablet of consumer, capsule, powder, pill, granule, unguentum, slow releasing preparation, quick releasing formulation, oral liquid.

9. the application of drug compound preparation in the medicine of preparation treatment diabetes as described in arbitrary such as claim 1-4.

10. the application of drug compound preparation in the medicine of preparation treatment hyperlipidemia with diabetes as described in arbitrary such as claim 1-4.