CN101559148B

CN101559148B - Pharmaceutical composition for treating diabetes and/or hyperlipemia and preparation method thereof

Info

Publication number: CN101559148B
Application number: CN 200810104422
Authority: CN
Inventors: 高学敏; 张建军; 欧丽娜; 李伟; 段震文; 郭树仁; 杜保民
Original assignee: Beijing Peking University WBL Biotech Co Ltd; Beijing University of Chinese Medicine
Current assignee: Beijing Peking University WBL Biotech Co Ltd; Beijing University of Chinese Medicine
Priority date: 2008-04-18
Filing date: 2008-04-18
Publication date: 2011-10-26
Anticipated expiration: 2028-04-18
Also published as: CN101559148A

Abstract

The invention discloses a pharmaceutical composition for treating diabetes and/or hyperlipemia and a preparation method thereof. The composition is made from five Chinese medicinal herbs: astragalus root, mulberry leaf, kudzuvine root, alisma rhizome and red rice; different components are subject to extraction, decoction, filtration, concentration and the like during a preparation process of the pharmaceutical composition to allow effective components to give full play; a large number of tests prove that the pharmaceutical composition has outstanding curative effect on the diabetes and/or hyperlipemia, safety and high safety and efficacy in clinical application.

Description

A kind of pharmaceutical composition and preparation method for the treatment of diabetes and/or hyperlipemia

Technical field

The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of pharmaceutical composition for the treatment of diabetes and/or hyperlipemia and preparation method thereof.

Background technology

Diabetes are a kind of common endocrine metabolism diseases, its basic pathology characteristics are the absolute or relative deficiency of insulin secretion, or peripheral tissues causes based on carbohydrate metabolism disturbance insulin insensitivity, comprises a kind of systemic disease of fat, protein metabolism disorder.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 shows as increasing of blood triglyceride (TG) rising, the reduction of highdensity lipoprotein-cholesterol (HDL-C) level and LDL-C (LDL-C) unusually.Therefore, simple blood sugar control can not be eliminated trunk complication such as diabetics coronary heart disease fully, in the time of blood sugar control, must transfer the fat treatment.Traditional Chinese medical science tradition compound recipe is paid attention to integrally-regulated, and treating both the principal and secondary aspects of a disease in recent years, is showing great potential aspect the treatment diabetes merging hyperlipemia.

Summary of the invention

One object of the present invention is to disclose a kind of pharmaceutical composition for the treatment of diabetes and/or hyperlipemia; Another object of the present invention is to disclose this preparation of drug combination method.

The present invention seeks to be achieved through the following technical solutions:

The raw material of pharmaceutical composition of the present invention consists of:

Radix Astragali 400-700 weight portion Folium Mori 400-700 weight portion Radix Puerariae 220-320 weight portion

Rhizoma Alismatis 400-700 weight portion Monas cuspurpureus Went 20-100 weight portion.

The raw material composition of pharmaceutical composition of the present invention is preferably:

The Radix Astragali 555 weight portion Folium Mori 555 weight portion Radix Puerariaes 278 weight portions

Rhizoma Alismatis 555 weight portion Monas cuspurpureus Went 66.6 weight portions.

The Radix Astragali 650 weight portion Folium Mori 450 weight portion Radix Puerariaes 230 weight portions

Rhizoma Alismatis 650 weight portion Monas cuspurpureus Went 90 weight portions.

The Radix Astragali 450 weight portion Folium Mori 750 weight portion Radix Puerariaes 310 weight portions

Rhizoma Alismatis 450 weight portion Monas cuspurpureus Went 30 weight portions.

Pharmaceutical composition of the present invention adds conventional adjuvant, according to common process, make tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation.

Preparation of drug combination method of the present invention can also comprise:

Get the Radix Astragali, added the 60%-80% soak with ethanol 1-3 hour, reflux, extract, 2 times, for the first time add Radix Astragali 5-10 and doubly measure ethanol, extracted 0.5-2 hour, add Radix Astragali 4-8 for the second time and doubly measure ethanol, extracted 0.5-2 hour, and filtered, filtrate merges, vacuum≤-0.05Mpa, temperature 60-90 ℃ is reclaimed ethanol, and vacuum≤-0.06Mpa, temperature 60-90 ℃ is concentrated into the thick paste that relative density is 1.05-1.50, vacuum≤-0.06Mpa, temperature 60-90 ℃ of drying under reduced pressure, get pure promotion cream A, standby; Astragalus root dregs and Folium Mori were soaked 1-3 hour, decocted with water 2 times, add astragalus root dregs and Folium Mori 10-14 times water gaging for the first time, decocted 0.5-2 hour, and added astragalus root dregs and Folium Mori 8-12 times water gaging for the second time, decocted 0.5-2 hour, filter, collecting decoction, vacuum≤-0.06Mpa, temperature 60-90 ℃ is concentrated into the thick paste that relative density is 1.05-1.50, vacuum≤-0.06Mpa, temperature 60-90 ℃ of drying under reduced pressure gets the dried cream B of decocting in water, and be standby; Get Radix Puerariae, Rhizoma Alismatis and add soak with ethanol 14-18 hour of 60%-80%, reflux, extract, 2 times, the first time adds Radix Puerariae and Rhizoma Alismatis 4-8 doubly measures ethanol, extracted 0.5-2 hour, the second time adds Radix Puerariae and Rhizoma Alismatis 4-8 doubly measures ethanol, extracted 0.5-2 hour, and filtered, filtrate merges, vacuum≤-0.05Mpa, temperature 60-90 ℃ is reclaimed ethanol, and vacuum≤-0.06Mpa, temperature 60-90 ℃ is concentrated into relative density is 1.05～1.50 thick paste, vacuum≤-0.06Mpa, temperature 60-90 ℃ of drying under reduced pressure gets pure promotion cream C, and be standby; Above alcohol promotion cream A and C, the dried cream B of decocting in water are pulverized, cross 80 mesh sieves, mix, standby; Get Monas cuspurpureus Went, microcrystalline Cellulose and said extracted thing mixed powder mix homogeneously, wherein the weight of microcrystalline Cellulose accounts for the 8%-18% of finished product gross weight, granulate, cross 30 mesh sieve granulate, the magnesium stearate that adds finished product gross weight 0.5%-3% again, mixing adds conventional adjuvant according to a conventional method and makes tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation.

Preparation of drug combination method of the present invention is preferably:

Get the Radix Astragali, add 70% soak with ethanol 2 hours, reflux, extract, 2 times, add for the first time 7 times of amounts of Radix Astragali ethanol, extracted 1 hour, add 6 times of amounts of Radix Astragali ethanol for the second time, extracted 1 hour, and filtered, filtrate merges, vacuum≤-0.05Mpa, ethanol is reclaimed in temperature≤70 ℃, and vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, and temperature≤70 ℃ drying under reduced pressure, get pure promotion cream A, standby; Astragalus root dregs and Folium Mori were soaked 2 hours, decocted with water 2 times, add astragalus root dregs and 12 times of water gagings of Folium Mori for the first time, decocted 1 hour, and added astragalus root dregs and 10 times of water gagings of Folium Mori for the second time, decocted 1 hour, filter, collecting decoction, vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets the dried cream B of decocting in water, and is standby; Get Radix Puerariae, Rhizoma Alismatis and added 70% soak with ethanol 16 hours, reflux, extract, 2 times adds 6 times of amounts of Radix Puerariae and Rhizoma Alismatis ethanol for the first time, extracted 1 hour, and added 5 times of amounts of Radix Puerariae and Rhizoma Alismatis ethanol for the second time, extracted 1 hour, filter, filtrate merges, vacuum≤-0.05Mpa, 70 ℃ of temperature reclaim ethanol, and vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets pure promotion cream C, and is standby; Above alcohol promotion cream A and C, the dried cream B of decocting in water are pulverized, cross 80 mesh sieves, mix, standby; Get Monas cuspurpureus Went, microcrystalline Cellulose and said extracted thing mixed powder mix homogeneously, wherein the weight of microcrystalline Cellulose accounts for 10.4% of finished product gross weight, granulate, cross 30 mesh sieve granulate, the magnesium stearate that adds finished product gross weight 2% again, mixing adds conventional adjuvant according to a conventional method and makes tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation.

Description of drawings

Fig. 1-1 merges the influence of hyperlipidemia rats pancreatic tissue pathomorphism to artificial diabetes for pharmaceutical composition of the present invention to Fig. 1-7.

Fig. 2-1 merges the influence of hyperlipidemia rats liver organization pathomorphism to artificial diabetes for pharmaceutical composition of the present invention to Fig. 2-7.

Fig. 3-1 causes the influence of diabetes rat pancreas tectology to STZ for medicament composition capsule of the present invention to Fig. 3-6.

Fig. 4-1 causes the morphologic influence of diabetes rat liver organization for medicament composition capsule of the present invention to STZ to Fig. 4-6.

Fig. 5 is this bright normal mouse glucose tolerance curve.

Fig. 6 is the body weight change of Carnis Coturnicis japonicae during the administration of the present invention.

Wherein:

Fig. 1-1 be normal control group pancreas HE dyeing photo 20 *

Rounded or the elliptical erythrocyte group of rats in normal control group islets of langerhans, boundary clear is scattered between the pancreatic acini, and cell mass is not of uniform size, regular shape, quantity is more, and light the dying of endochylema is baby pink, examines circular engrain.

Fig. 1-2 be model group pancreas HE dyeing photo 20 *

Model group rat Langerhans islet quantity reduces, and it is sparse to distribute, and the islets of langerhans border is irregular, shows as the cellular swelling, and kytoplasm is painted shallow, karyopyknosis.

Fig. 1-3 be metformin group pancreas HE dyeing photo 20 *

Visible dispersive nido islet distribution between metformin control rats acinus, quantity have slightly than model group and increase the islets of langerhans neat in edge.

Fig. 1-4 be Xuezhikang group pancreas HE dyeing photo 20 *

Xuezhikang group rat Langerhans islet quantity reduces, and it is sparse to distribute, the islets of langerhans neat in edge, and kytoplasm is painted shallow.

Fig. 1-5 be the peaceful high dose group pancreas of the bent glycolipid of stilbene HE dyeing photo 20 *

The peaceful high dose group rat of the bent glycolipid of stilbene pancreas quantity reduces, and it is sparse to distribute, the islets of langerhans neat in edge, and kytoplasm is painted shallow.

Fig. 1-6 be the bent glycolipid of stilbene peaceful in dosage group pancreas HE dyeing photo 20 *

Visible dispersive nido between dosage group rat acinus during the bent glycolipid of stilbene is peaceful, islet distribution, quantity have slightly than model group and increase the islets of langerhans neat in edge.

Fig. 1-7 be the peaceful low dose group pancreas of the bent glycolipid of stilbene HE dyeing photo 20 *

Visible dispersive nido islet distribution between the peaceful low dose group rat of the bent glycolipid of stilbene acinus, quantity have slightly than model group and increase the islets of langerhans neat in edge.

Fig. 2-1 be normal control rats liver HE dyeing photo 20 *

Fig. 2-2 be model control group rat liver HE dyeing photo 20 *

Fig. 2-3 be metformin control rats liver HE dyeing photo 20 *

Fig. 2-4 be Xuezhikang control rats liver HE dyeing photo 20 *

Fig. 2-5 be the peaceful high dose group rat liver of the bent glycolipid of stilbene HE dyeing photo 20 *

Fig. 2-6 be the bent glycolipid of stilbene peaceful in dosage group rat liver HE dyeing photo 20 *

Fig. 2-7 be the peaceful low dose group rat liver of the bent glycolipid of stilbene HE dyeing photo 20 *

Fig. 3-1 be normal control group pancreas HE dyeing photo 400 *

Fig. 3-2 be model group pancreas HE dyeing photo 400 *

Fig. 3-3 be metformin matched group pancreas HE dyeing photo 400 *

Fig. 3-4 be the peaceful high dose group pancreas of the bent glycolipid of stilbene HE dyeing photo 400 *

Fig. 3-5 be the bent glycolipid of stilbene peaceful in dosage group pancreas HE dyeing photo 400 *

Fig. 3-6 be the peaceful low dose group pancreas of the bent glycolipid of stilbene HE dyeing photo 400 *

Fig. 4-1 be normal control group liver HE dyeing photo 100 *

Fig. 4-2 be model control group liver HE dyeing photo 100 *

Fig. 4-3 be metformin matched group liver HE dyeing photo 100 *

Fig. 4-4 be the peaceful high dose group liver of the bent glycolipid of stilbene HE dyeing photo 100 *

Fig. 4-5 be the bent glycolipid of stilbene peaceful in dosage group liver HE dyeing photo 100 *

Fig. 4-6 be the peaceful low dose group liver of the bent glycolipid of stilbene HE dyeing photo 100 *

The present invention is directed to Chinese medicine six kind new medicines--drug combination preparation of the present invention has carried out prescription, technology, blood sugar lowering, blood fat reducing pharmacodynamics and toxicology thereof and has studied.Drug combination preparation of the present invention is by Chinese medicine of the five flavours such as the Radix Astragali, Folium Mori, Monas cuspurpureus Went, function supplementing QI and nourishing YIN, promoting the production of body fluid to quench thirst, blood stasis dispelling the turbid descending.Cure mainly deficiency of both vital energy and Yin, the diabete of the turbid mutual resistance of the stasis of blood, disease is seen thirsty and dry pharynx, the polydipsia polyuria, breast gastral cavity painful abdominal mass is vexed, fatigue and weakness or see the loose stool, corpulent tongue is tender or have ecchymosis concurrently; Type 2 diabetes mellitus and/or hyperlipemia are seen above-mentioned patient.Drug combination preparation of the present invention can be regulated the diabetes rat carbohydrate metabolism disturbance that streptozotocin (STZ) brings out, increase the storage of sugar, regulate the diabetic mice carbohydrate metabolism disturbance of model induced by alloxan, type 2 diabetes mellitus and/or hyperlipemia there are the obvious treatment effect, thereby had not only had blood sugar lowering but also had the effect of blood fat reducing.

Experiment and embodiment are used to further specify but are not limited to the present invention below.

Experimental example 1 to experimental example 11 all adopts following test material and experimental technique:

1.1 test material

1.1.1 animal

The Wistar male rat, secondary, body weight 180-200g.The quality certification number: SCXK (capital) 2002-0003 number.Provide by Beijing Vital River Experimental Animals Technology Co., Ltd..

1.1.2 medicine

Be subjected to reagent: drug combination preparation of the present invention (QQTZN), Beijing University's dimension letter bio tech ltd provides; Lot number: 20060801, intending clinical people's consumption is 18.1g medical material/day, 0.30g medical material/kg (people presses the 60kg weighing machine).

Positive control drug: glucophage (metformin hydrochloride): Sino-U.S. executes in Shanghai expensive precious pharmaceutical Co. Ltd; Lot number: 0601076, the rat consumption is 0.254g/kg.Compound method: get tablet and add the deionized water grinding, be mixed with solution.XUEZHIKANG JIAONANG, Beijing University's dimension letter bio tech ltd provides; Lot number: 20060508, the rat consumption is 0.120g/kg.Compound method: take out capsule 's content, be mixed with solution with deionized water.

1.1.3 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 (Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.); Streptozotocin (U.S. sigma company); Insulin radioimmunological kit (Beijing China English biotechnology research institute)

1.2 experimental technique

1.2.1 set up the diabetes hyperlipaemia animal model: select 95 of male Wistar rats, body weight 180～200g, normally feed a week after, be divided into normal control group and model group by the body weight randomized blocks, wherein the normal control group is 10,85 of model group.Normal control 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 ^-1The dosage disposable celiac is injected 2% streptozotocin solution (before facing usefulness, 0.1M citrate buffer solution with PH4.2 is mixed with 2% solution), normal control group lumbar injection is with dosage citric acid-sodium citrate buffer, detect fasting glucose, blood fat behind the 72h, based on fasting glucose＞11mmolL-1, double see raise cholesterol (TC), serum triglycerides (TG) content to have the rat of significant difference with the normal control group be that successful model is included experiment in.

1.2.2 grouping and administration: keep 10 rats of normal control group.Select 60 of standard compliant model group rats, according to fasting blood sugar, adopt randomized blocks to be divided into 6 groups, be respectively model control group, positive drug metformin matched group, positive drug Xuezhikang matched group, the high, medium and low dosage group of pharmaceutical composition of the present invention, 10 every group.Blank group and model control group are irritated stomach with the volume distilled water; Positive drug metformin matched group is irritated stomach metformin solution (254mg/kg); Positive drug XUEZHIKANG JIAONANG matched group is irritated stomach XUEZHIKANG JIAONANG solution (120mg/kg); The pharmaceutical composition of the present invention that the high, medium and low dosage group of pharmaceutical composition of the present invention is irritated the stomach various dose respectively (is equivalent to 16,8 and 4 times of this medicine rat dose,equivalent, promptly 4.82,2.41 and the 1.21g crude drug/kg).In continuous 4 weeks, respectively organize rat during the medication treatment and all raise with normal diet ad lib, drinking-water every day.

1.2.3 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 blood fat four (TG, TC, 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 standby.The ventral aorta blood sampling is injected a clean tube and is left standstill, 4 ℃, 3500rmin-1, centrifugal 10min, separation of serum, except that FBG (fasting glucose) detected immediately, all the other serum, sample were sub-packed in the frozen pipe of 1.5mL ,-20 ℃ of cold storage of refrigerator relevant biochemistry to be checked, put and exempted from index.

1.2.4 the preparation of tissue samples: after the ventral aorta blood sampling, cut open rapidly and get the pancreas in rat portion of tissue, be soaked in fix in the Bouin solution to be checked.Cut open and get the rat liver portion of tissue, be soaked in fix in 10% formalin to be checked

1.2.5 detection index:

Fasting glucose is measured (employing glucose oxidase method)

The mensuration of glucose in urine (employing Tes-Tape)

Cholesterol (TC) assay (enzymic colorimetric)

Triglyceride (TG) assay (enzymic colorimetric)

Low density cholesterol lipoprotein (LDL-C) assay (the polyvinyl sulfuric acid sedimentation method)

High density cholesterol lipoprotein (HDL-C) assay (phosphotungstic acid-magnesium precipitate method)

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

Insulin sensitivity (sensitivity): IAI=1/FBG * FINS (therefore value is nonnormal distribution, so get its natural logrithm during calculating)

Free serum fatty acid (FFA) assay (colorimetry)

Pancreas, liver organization pathomorphism.

1.2.6 statistical method: data represent that with mean ± standard deviation each organizes the relatively employing t check in groups between the data.

Experimental example 1 pharmaceutical composition of the present invention merges the influence of hyperlipidemia rats blood glucose to artificial diabetes

The results are shown in Table 1.The result shows that model group is compared blood glucose with blank group before the injection STZ does not have significant difference, and before the administration, model group is compared blood glucose with the blank group and obviously raise, and there were significant differences (P＜0.01), and other each administration groups are compared no significant difference with model group; After 4 weeks of administration, metformin group, the high, medium and low dosage group of QQTZN blood sugar level all have significant decline (P＜0.05) than model group.Administration 6 week, the back blood glucose were generally than administration 4 all blood sugar increasing, analyze with 5 weeks of administration after the carbohydrate tolerance that carries out to test the influence that rat is caused relevant.After 6 weeks of administration, metformin group, the high, medium and low dosage group of QQTZN blood sugar level all have significant decline (P＜0.05) than model group.(seeing Table 1)

Table 1 pair artificial diabetes merges the glycometabolic influence of hyperlipidemia rats (x ± s) (n=8)

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 2 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats oral glucose tolerance to artificial diabetes

The results are shown in Table 2.To each group glucose tolerance curve integration, after origin correction, get area under curve (AUC).By the result as can be known, area is 539.62mmol/Lh under the blank group glucose tolerance curve, and area 1385.40mmol/Lh under the model group glucose tolerance curve compares obvious rising with the blank group; Area is 671.39mmol/Lh under the metformin group glucose tolerance curve, obviously reduces area under the glucose tolerance curve than model group; Area is 915.75mmol/Lh under the Xuezhikang group glucose tolerance curve, obviously reduces area under the glucose tolerance curve than model group; The high, medium and low dosage group of QQTZN can reduction glucose tolerance curve in various degree under area.

Table 2 pair artificial diabetes merges influence (x ± s) (n=8) of hyperlipidemia rats oral glucose tolerance

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 3 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats glucose in urine to artificial diabetes

The results are shown in Table 3.The result shows that model group is compared level of sugar with the blank group and obviously raise, and there were significant differences (P＜0.01), and the metformin group is compared remarkable reduction (P＜0.01) with model group; The QQTZN high dose group is compared with model group, and level of sugar obviously reduces (P＜0.05).

Table 3 pair artificial diabetes merges influence (x ± s) (n=8) of hyperlipidemia rats level of sugar

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 4 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats glucose in urine empty stomach serum insulin content and insulin sensitivity index to artificial diabetes

The results are shown in Table 4.The result shows, model group is compared serum insulin content and raise not obviously with the blank group, but insulin sensitivity index obviously reduces, and there were significant differences (P＜0.01); Positive drug metformin matched group is compared serum insulin levels and is significantly reduced (P＜0.01) with model group, insulin sensitivity index obviously raise (P＜0.01); The QQTZN high dose group is compared with model group, and serum insulin levels obviously reduces (P＜0.05), insulin sensitivity index obviously raise (P＜0.01).Among positive drug Xuezhikang matched group, the QQTZN, low dose group compares with model group, serum insulin levels does not have significant change, but insulin sensitivity sex index obviously raises (P＜0.01).

Table 4 pair artificial diabetes merges influence (x ± s) (n=8) of hyperlipidemia rats empty stomach serum insulin content and insulin sensitivity index

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 5 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats pancreatic tissue pathomorphism to artificial diabetes

The results are shown in Figure 1.Rounded or the elliptical erythrocyte group of rats in normal control group islets of langerhans, boundary clear is scattered between the pancreatic acini, and cell mass is not of uniform size, regular shape, quantity is more, and light the dying of endochylema is baby pink, examines circular engrain.Model group rat Langerhans islet quantity reduces, and it is sparse to distribute, and the islets of langerhans border is irregular, shows as the cellular swelling, and kytoplasm is painted shallow, karyopyknosis.Visible dispersive nido islet distribution between metformin control rats acinus, islets of langerhans quantity have slightly than model group and increase the islets of langerhans neat in edge.Xuezhikang group rat Langerhans islet quantity reduces, and it is sparse to distribute, the islets of langerhans neat in edge.Each dosage group of QQTZN increases than model group rat gland island distribution number, and wherein high dose group rat Langerhans islet quantity is less relatively, and the islets of langerhans boundary is clearer.

Experimental example 6 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats serum TC to artificial diabetes

The results are shown in Table 5.The result shows, after the high glucose and high fat beverage fed for 8 weeks, the blank group serum TC of model group obviously raises, and there were significant differences (P＜0.01), behind the injection STZ, model group is compared serum TC with the blank group and is further raise, and there were significant differences (P＜0.01), and other each administration groups are compared no significant difference with model group; After 2 weeks of administration, Xuezhikang group TC obviously descends than model group, and there were significant differences (P＜0.01); After 4 weeks of administration, each administration group TC all has significant decline (P＜0.01) than model group.After 6 weeks of administration, each administration group serum TC all has significant decline (P＜0.01) than model group.With compare before the administration, the model group Serum TC descends to some extent, analyze with administration during to stop the lipid removing ability of high fat diet and rat self more relevant.

Table 5 pair artificial diabetes merges hyperlipidemia rats influence (x ± s) (n=8) of serum TC on an empty stomach

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 7 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats serum TG to artificial diabetes

The results are shown in Table 6.The result shows that model group is compared serum TG with blank group before the injection STZ does not have significant difference, and before the administration, model group is compared serum TG with the blank group and obviously raise, and there were significant differences (P＜0.05), and other each administration groups are compared no significant difference with model group; After 4 weeks of administration, Xuezhikang group, QQTZN height, middle dosage group serum TG level all have significant decline (P＜0.05) than model group.After 6 weeks of administration, each administration group serum TG level all has significant decline (P＜0.05) than model group.

Table 6 pair artificial diabetes merges hyperlipidemia rats influence (x ± s) (n=8) of serum TG on an empty stomach

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 8 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats Serum HDL-C to artificial diabetes

The results are shown in Table 7.The result shows that after 2 weeks of administration, model group is compared Serum HDL-C with the blank group and obviously reduced, and there were significant differences (P＜0.01), and Xuezhikang group, metformin group, QQTZN height, middle dosage group are compared with model group all remarkable rising (P＜0.05); After 4 weeks of administration, Xuezhikang group and QQTZN high dose group Serum HDL-C level all have remarkable rising (P＜0.05) than model group.After 6 weeks of administration, each administration group Serum HDL-C level all has remarkable rising (P＜0.05) than model group.

Table 7 pair artificial diabetes merges hyperlipidemia rats influence (x ± s) (n=8) of Serum HDL-C on an empty stomach

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 9 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats serum LDL-C to artificial diabetes

The results are shown in Table 8.The result shows that after 2 weeks of administration, model group is compared serum LDL-C with the blank group and obviously raise, and there were significant differences (P＜0.01), and the Xuezhikang group is compared remarkable rising (P＜0.01) with model group; After 4 weeks of administration, model group is compared serum LDL-C and is significantly raise (P＜0.01) with the blank group, and other each administration group serum LDL-C levels all have significant decline (P＜0.05) than model group.After 6 weeks of administration, each administration group serum LDL-C level all has further significant descend (P＜0.05) than model group.

Table 8 pair artificial diabetes merges hyperlipidemia rats influence (x ± s) (n=8) of serum LDL-C on an empty stomach

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 10 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats free serum content of fatty acid to artificial diabetes

The results are shown in Table 9.Colorimetric detection result shows: rats in normal control group serum FFA content is 417.59 ± 78.90 μ molL ^-1, model group is 1017.93 ± 129.74 μ molL ^-1, the normal matched group serum FFA content of model group significantly raise (P＜0.01).The administration group is compared with model group, and the high, medium and low dosage group of QQTZN serum FFA content is respectively 588.57 ± 65.01 μ molL ^-1, 575.19 ± 75.14 μ molL ^-1, 552.90 ± 73.92 μ molL ^-1, all than model group significantly descend (P＜0.01).

Table 9 pair artificial diabetes merges hyperlipidemia rats influence (x ± s) (n=8) of serum FFA on an empty stomach

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

Compare #P＜0.05, ##P＜0.01 with the blank group

Experimental example 11 pharmaceutical compositions of the present invention merge the influence of hyperlipidemia rats liver organization pathomorphism to artificial diabetes

The results are shown in Figure 2.Rats in normal control group hepatic tissue structural integrity, clear, the lobules of liver structure is normal, and the hepatocyte queueing discipline radially distributes around central vein.The hepatic sinusoid clear in structure, no abnormal change.Hepatocyte is polygon, and endochylema is even, and karyomorphism is normal.Model group rats'liver lobule boundary is unclear, the hepatocyte arrangement disorder, and steatosis appears in most of hepatocyte, as seen differs in size in the endochylema, and the fat that quantity differs drips cavity, does not see that the liver interstitial fibrosis changes.Metformin group rats'liver lobule and hepatic sinusoid clear in structure, the cell marshalling, the cell lactone drips cavity to be reduced, and liver fat range degree improves than model group.Xuezhikang group rats'liver lobule and hepatic sinusoid clear in structure, the cell marshalling, the cell lactone drips cavity significantly to be reduced, and liver fat range degree has clear improvement than model group.The high, medium and low dosage group of QQTZN rats'liver lobule and hepatic sinusoid clear in structure, the cell marshalling, the cell lactone drips cavity significantly to be reduced, and liver fat range degree has clear improvement than model group.Chinese medicine counterevidence side group rats'liver lobule and hepatic sinusoid clear in structure, cell is arranged more neat, and the cell lactone drips cavity to be reduced than model group, and liver fat range degree has improvement slightly than model group, but not as good as QQTZN treatment group.

Experimental example 12 to experimental example 18 all adopts following test material and experimental technique:

Laboratory animal: healthy male wistar rat, body weight 190-210g available from dimension tonneau China Experimental Animal Center, raises in the zooperies of 18～22 ℃ of cleaning levels indoorly, and the animal quality certification number is SCXK (capital) 2002-0003.

Positive control drug: glucophage (metformin hydrochloride): Sino-U.S. executes in Shanghai expensive precious pharmaceutical Co. Ltd; Lot number: 0604078, the rat consumption is 0.250g/kg.Compound method: get tablet and add the deionized water grinding, be mixed with solution.

Main agents: glucose assays test kit (Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.); Insulin (INS) radioimmunological kit, glucagon (PG) radioimmunological kit (Beijing China English biotechnology research institute); 20070829), inose unit and liver glycogen measure test kit (lot number: 20070830) bio-engineering research institute is built up in Nanjing saccharifying serum albumin (GSP) is measured test kit (lot number:; Streptozotocin (STZ, U.S. Sigma company)

Experimental technique: healthy male wistar rat is got in the foundation of model, body weight 190g-210g, adaptability feed 1 week the back be divided into 2 groups on normal control and model at random by body weight.Before setting up model, the equal fasting of normal control group and model group (can't help water) 24h, model group is with 60mgkg ^-1Disposable quick lumbar injection 2% streptozotocin of dosage (face with before, be mixed with 2% solution) with the 0.1M citrate buffer solution of PH4.2, the isopyknic buffer of normal control group lumbar injection.Get blood in eye socket behind the 72h, leave standstill back centrifugal (3000rpm, 10min) separation of serum, press the operation of glucose assays test kit description, measure on semi-automatic biochemical analyzer and detect FBG, reject the too high or too low person of blood glucose, the rat of choosing blood glucose value＞11.1mmol/L is as experimental model.

The grouping administration keeps 10 rats of normal control group.Select 60 of standard compliant model group rats,, adopt randomized blocks to be divided into 5 groups according to fasting blood sugar.(1) the blank group is 10: irritate stomach with the volume distilled water; (2) model control group is 13: irritate stomach with the volume distilled water; (3) positive drug metformin hydrochloride matched group is 13: irritate gastric hydrochloric acid metformin solution, every day, dosage was 250mgkg ^-1(4) medicament composition capsule high dose group of the present invention is 12: irritate stomach medicament composition capsule high dose of the present invention solution, every day, dosage was 4.82gkg ^-1(be equivalent to the clinical consumption of people 16 times); (5) 12 of dosage groups in the medicament composition capsule of the present invention: irritate dosage solution in the stomach medicament composition capsule of the present invention, every day, dosage was 2.41gkg ^-1(be equivalent to the clinical consumption of people 8 times); (6) medicament composition capsule low dose group of the present invention is 10: gavage medicament composition capsule low dosage solution of the present invention, every day, dosage was 1.21gkg ^-1(be equivalent to the clinical consumption of people 4 times).Each is organized and irritates stomach every day 1 time, and continuous 28 days, each medication volume was irritated stomach 1.0mL by every 100g body weight and calculated.Respectively organize mice during the medication treatment and all raise with normal diet ad lib, drinking-water every day.

Being prepared in during the medication treatment of blood sample, 1 eye socket venous sinus blood sampling weekly, 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, abdominal aortic blood injects a clean tube and leaves standstill separation of serum, detect outside FBG detects immediately, all the other blood serum samples are sub-packed in the frozen pipe of 1.5mL ,-20 ℃ of cold storage of refrigerator relevant biochemistry to be checked, put and exempt from index.

The preparation of tissue samples is cutd open rapidly and is got pancreas in rat, liver portion of tissue after putting to death rat, be soaked in fix in 10% formalin to be checked; Other gets a part of hepatic tissue liquid nitrogen cryopreservation, is used for the test section index.

Observation index and detection method

(fasting blood glucose FBG) measures: adopt glucose oxidase method fasting glucose.

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

Glucagon assay: adopt radio immunoassay

Saccharifying serum albumin (GSP) assay: adopt the fructosamine method

Flesh, hepatic glycogen content are measured: the sulphuric acid anthrone method

Insulin sensitivity sex index (insulin sensitivity index, ISI): ISI=1/FBG * FINS (therefore value is nonnormal distribution, so get its natural logrithm during calculating).

Tissue pathology checking: take out and be soaked in fixed liver organization, pancreatic tissue in 10% formalin, conventional washing, dehydration, paraffin embedding, section, HE dyeing, light microscopic is observed pathological change down.

Statistical method: (x ± s) expression uses the SPSS12.0 statistical software to experimental data, and utilization one factor analysis of variance (one-way ANOVA) carries out comparing between each group, and significance level is a standard with 0.05 and 0.01 with mean ± standard deviation.

Experimental example 12 medicament composition capsules of the present invention are to the influence of experimental diabetic rats blood glucose

Change of blood sugar situation during the table 10 tissue of experimental diabetic mice medication treatment (x ± SD)

Annotate: with model group than * P＜0.05**P＜0.01

Serum biochemistry is learned testing result and is shown: before the medication treatment, normal control group blood glucose value is 2.78 ± 0.83mmolL-1, the model group blood glucose value is 18.37 ± 3.84mmolL-1, model group and normal control group are relatively, 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).After 4 weeks of administration, metformin group, the high, medium and low dosage group of pharmaceutical composition of the present invention blood sugar level all have significant decline (P＜0.01) than model group.

Experimental example 13 medicament composition capsules of the present invention are to the influence of experimental diabetic rats saccharifying serum albumin (GSP)

4 week of table 11 treatment back experimental diabetic rats saccharifying serum albumin (GSP) result (x ± SD, n=10)

Annotate: with model group than * P＜0.05**P＜0.01

The result shows, after the administration 4 week treatment, model group is compared saccharifying serum albumin (GSP) level and is obviously raise with the blank group, and there were significant differences (P＜0.01), and metformin group, drug regimen object height of the present invention, middle dosage group are compared obvious reduction (P＜0.05) with model group.

Experimental example 14 medicament composition capsules of the present invention are to the influence of experimental diabetic rats glucose in urine

4 week of table 12 treatment back experimental diabetic rats urinary glucose determination result

The result shows that model group is compared level of sugar with the blank group and obviously raise, and metformin group, pharmaceutical composition high dose group of the present invention are compared level of sugar with model group and obviously reduced.

Experimental example 15 medicament composition capsules of the present invention are to the influence of experimental diabetic rats serum insulin, glucagon, insulin sensitivity index level

Table 13 experimental diabetic rats treatment back serum insulin, glucagon, insulin sensitivity index situation (x ± SD)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01, with the normal control group than #P＜0.05##P＜0.01

The result shows that model group is compared serum insulin levels with the normal control group and obviously reduced, and the glucagon level obviously raises, and insulin sensitivity index obviously reduces, and there were significant differences (P＜0.01); Positive drug metformin group is compared serum insulin levels with model group and is slightly raise, and glucagon slightly reduces, but zero difference (P＞0.05), and insulin sensitivity index obviously raises (P＜0.01); The high, medium and low dosage group of pharmaceutical composition of the present invention is compared with model group, and serum insulin obviously raises (P＜0.01), and the glucagon level obviously reduces (P＜0.01, P＜0.05), insulin sensitivity index obviously raise (P＜0.01).

Experimental example 16 medicament composition capsules of the present invention are to the influence of experimental diabetic rats hepatic glycogen, muscle glycogen level

Glycogen content result in table 14 treatment 4 all backs experimental diabetic rats hepatic tissues, the skeletal muscle tissue (x ± SD, n=10)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

The result shows that model group obviously reduces with the glycogen content that the blank group is compared in hepatic tissue, the skeletal muscle tissue, and there were significant differences (P＜0.01); Positive drug metformin matched group is compared hepatic glycogen, muscle glycogen level obviously raise (P＜0.05) with model group; Drug regimen object height of the present invention, middle low dose group are compared the hepatic glycogen level and are obviously raise (P＜0.01) with model group, slightly raise and zero difference (P＞0.05) but compare the high, medium and low dosage group of pharmaceutical composition of the present invention muscle glycogen level with model group.

Experimental example 17 medicament composition capsules of the present invention cause the influence of diabetes rat pancreas tectology to STZ

The light microscopic result shows (Fig. 3), the rounded or oval-shaped cell mass of rats in normal control group islets of langerhans, and boundary clear is scattered between the pancreatic acini, and cell mass is not of uniform size, regular shape, quantity is more, and light the dying of endochylema is baby pink, examines circular engrain.Model group mouse islets quantity reduces, and it is sparse to distribute, and the islets of langerhans border is irregular, shows as the cellular swelling, and kytoplasm is painted shallow, and karyopyknosis does not see that the islets of langerhans interstitial fibrosis changes.Visible dispersive nido islet distribution between medicament composition capsule high dose group of the present invention, middle dosage group, low dose group, metformin control rats acinus, quantity have slightly than model group and increase the islets of langerhans neat in edge.

Experimental example 18 medicament composition capsules of the present invention cause the morphologic influence of diabetes rat liver organization to STZ

The light microscopic result shows (Fig. 4), rats in normal control group hepatic tissue structural integrity, clear, and the lobules of liver structure is normal, and the hepatocyte queueing discipline radially distributes around central vein.The hepatic sinusoid clear in structure, no abnormal change.Hepatocyte is polygon, and endochylema is even, and karyomorphism is normal.Model group rats'liver lobule boundary is unclear, and the hepatocyte arrangement disorder does not see that the liver interstitial fibrosis changes.The high, medium and low dosage group of pharmaceutical composition of the present invention rats'liver lobule and hepatic sinusoid clear in structure, the cell marshalling, liver fat range degree has in various degree improvement than model group.

Experimental example 19 to experimental example 20 all adopts following test material and experimental technique:

The healthy male ICR mouse of laboratory animal, body weight 20-24g available from dimension tonneau China Experimental Animal Center, raises in the zooperies of 18～22 ℃ of cleaning levels indoorly, and the animal quality certification number is SCXK (capital) 2002-0003.

Experimental drug is subjected to reagent: drug combination preparation of the present invention (QQTZN), and Beijing University's dimension letter bio tech ltd provides; Lot number: 20060801, intending clinical people's consumption is 18.1g medical material/day, 0.30g medical material/kg (people presses the 60kg weighing machine).

Positive control drug: glucophage (metformin hydrochloride): Sino-U.S. executes in Shanghai expensive precious pharmaceutical Co. Ltd; Lot number: 0604078, the mice consumption is 0.300g/kg.Compound method: get tablet and add the deionized water grinding, be mixed with solution.

Main agents

Glucose assays test kit (lot number 060631) Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.

INS radioimmunoassay kit Beijing China English biotechnology research institute

Alloxan Fluka company product

The foundation of experimental technique model: get healthy male ICR mouse, body weight 20g-24g, adaptability feed 1 week the back be divided into 2 groups on normal control and model at random by body weight.Before setting up model, the equal fasting of normal control group and model group (can't help water) 24h, model group is with 200mgkg ^-1The dosage disposable celiac is injected 2% alloxan solution (before facing usefulness, get an amount of alloxan, prepare with normal saline), normal control group lumbar injection is got blood in eye socket with the dosage normal saline behind the 72h, leave standstill the centrifugal (3000rpm in back, 10min) separation of serum is pressed the operation of glucose assays test kit description, measures on semi-automatic biochemical analyzer and detects 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.

The grouping administration keeps 10 mices of normal control group.Select 50 of standard compliant model group rats,, adopt randomized blocks to be divided into 5 groups, 10 every group according to fasting blood sugar.(1) blank group: irritate stomach with the volume distilled water; (2) model control group: irritate stomach with the volume distilled water; (3) positive drug metformin hydrochloride matched group: irritate gastric hydrochloric acid metformin solution, every day, dosage was 300mgkg ^-1(4) medicament composition capsule high dose group of the present invention: irritate stomach medicament composition capsule high dose of the present invention solution, every day, dosage was 6.04gkg ^-1(be equivalent to the clinical consumption of people 20 times); (5) dosage group in the medicament composition capsule of the present invention: irritate dosage solution in the stomach medicament composition capsule of the present invention, every day, dosage was 3.02gkg ^-1(be equivalent to the clinical consumption of people 10 times); (6) medicament composition capsule low dose group of the present invention: gavage medicament composition capsule low dosage solution of the present invention, every day, dosage was 1.51gkg ^-1(be equivalent to the clinical consumption of people 5 times).Each is organized and irritates stomach every day 1 time, and continuous 28 days, each medication volume was irritated stomach 0.2mL by every 10g body weight and calculated.Respectively organize mice during the medication treatment and all raise with normal diet ad lib, drinking-water every day.

Being prepared in during the medication treatment of blood sample, 1 eye socket venous sinus blood sampling weekly, 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, detect outside FBG detects immediately, all the other blood serum samples are sub-packed in the frozen pipe of 1.5mL ,-20 ℃ of cold storage of refrigerator relevant biochemistry to be checked, put and exempt from index.

Observation index and detection method

FBG measures: adopt glucose oxidase method.

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

Insulin sensitivity sex index (insulin sensitivity index, ISI): ISI=1/FBG * FINS.

Statistical method: (x ± s) expression adopts the SPSS12.0 statistical software to experimental data, and relatively, significance level was a standard with 0.05 and 0.01 between utilization one factor analysis of variance (one-way ANOVA) carried out respectively organizing with mean ± standard deviation.

Experimental example 19 medicament composition capsules of the present invention are to the influence of tissue of experimental diabetic mice blood glucose

Change of blood sugar situation during the table 15 tissue of experimental diabetic mice medication treatment (x ± SD, n=10)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

Serum biochemistry is learned testing result and is shown: before the medication treatment, normal control group blood glucose value is 4.06 ± 0.73mmolL-1, the model group blood glucose value is 26.06 ± 3.17mmolL-1, model group and normal control group are relatively, 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).

Experimental example 20 to experimental example 22 all adopts following test material and experimental technique:

The healthy ICR mice of laboratory animal, male and female half and half, body weight 18-20g available from dimension tonneau China Experimental Animal Center, raises in the zooperies of 18～22 ℃ of cleaning levels indoorly, and the animal quality certification number is SCXK (capital) 2002-0003.

Main agents

Sulphuric acid (AR, lot number 20050815) Beijing Chemical Plant

Glucose (AR, lot number 050606) Beijing chemical reagents corporation

Trichloroacetic acid (AR, lot number 061227) Xing Jin chemical plant, Beijing

Anthrone (AR, lot number 20060820) Beijing chemical reagents corporation

DL-alanine (biochemical reagents, lot number 050425) Beijing chemical reagents corporation

Experimental technique grouping administration: normal ICR mice, after adaptability raised for 1 week,, adopt randomized blocks to be divided into 5 groups according to the body weight value.(1) blank group: irritate stomach with the volume distilled water; (2) positive drug metformin hydrochloride matched group: irritate gastric hydrochloric acid metformin solution, every day, dosage was 300mgkg ^-1(3) medicament composition capsule high dose group of the present invention: irritate stomach medicament composition capsule high dose of the present invention solution, every day, dosage was 6.04gkg ^-1(be equivalent to the clinical consumption of people 20 times); (4) dosage group in the medicament composition capsule of the present invention: irritate dosage solution in the stomach medicament composition capsule of the present invention, every day, dosage was 3.02gkg ^-1(be equivalent to the clinical consumption of people 10 times); (5) medicament composition capsule low dose group of the present invention: gavage medicament composition capsule low dosage solution of the present invention, every day, dosage was 1.51gkg ^-1(be equivalent to the clinical consumption of people 5 times).Each is organized and irritates stomach every day 1 time, and continuous 14 days, each medication volume was irritated stomach 0.2mL by every 10g body weight and calculated.Respectively organize mice during the medication and all raise with normal diet ad lib, drinking-water every day.Administration one week, the back measured carbohydrate tolerance, did the glyconeogenesis test after the two weeks, put to death animal at last and got liver and do the hepatic glycogen analysis.

Statistical method: each organizes experimental data, and (x ± s) represent adopts the SPSS12.0 statistical software, uses single factor variance (one-way ANOVA) analysis to carry out comparing between each group with mean ± standard deviation, p＜0.05 o'clock, show that difference has significance, p＜0.01 o'clock shows that difference has utmost point significance.

The experiment of experimental example 20 oral glucose tolerances

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 the normal control group is given the equivalent distilled water.Gavage glucose (2.5g/kg) behind the 1h, eye socket is got blood, biochemical instruments measure to after the sugar 0.5,1.0,2.0,3.0, the blood glucose value of 4.0h.According to measured blood glucose value, draw and respectively organize the blood glucose time graph, area under the calculated curve.The results are shown in Table 16.(Fig. 5)

Table 16 normal mouse mice carbohydrate tolerance test situation (x ± SD)

Annotate: with normal control group ratio ^*P＜0.05 ^*P＜0.01

After giving glucose, the mouse blood sugar level obviously raises, and reaches peak value during 0.5h, passes gradually in time, falls after rise, reaches normal level after 180 minutes.Medicament composition capsule height of the present invention, middle dosage can obviously reduce the peak value behind the mice glucose load, accelerate the falling speed of blood sugar level, and there were significant differences for blood glucose value when 0.5h and blank group (P＜0.05, P＜0.01).Metformin can significantly reduce the peak value behind the mice glucose load, accelerates blood glucose and falls speed after rise, and blood glucose value when 0.5h, 1.0h and normal control group have significant difference (P＜0.05, P＜0.01).

The test of experimental example 21 glyconeogenesis: after 2 weeks of administration, mice fasting 8 hours, eye socket is got blood, and biochemical instruments is measured fasting blood sugar (0min).Thereafter, by body weight 2g/kg dosage lumbar injection DL-alanine.Injection back 1h eye socket is got blood, blood glucose value when measuring 60min.

Behind the injection alanine, mouse blood sugar significantly raises.It is the glyconeogenesis of substrate that metformin can suppress with the alanine, compares variant (P＜0.05) with the normal control group; Though each dosage group of medicament composition capsule of the present invention has inhibition trend, not statistically significant (P＞0.05).The results are shown in Table 17.

Table 17 normal mouse mice glyconeogenesis test situation (x ± SD)

Annotate: with normal control group ratio ^*P＜0.05 ^*P＜0.0

The experiment of experimental example 22 liver glycogen Determination on content

Mice is put to death in the cervical vertebra dislocation of glyconeogenesis test back, takes by weighing liver 20-30mg fast, measures hepatic glycogen as follows.

(1) preparation of anthrone reagent: take by weighing anthrone 40mg, put into the concentrated sulphuric acid of 20mL, use immediately after the stirring and dissolving rapidly (now with the current).

(2) preparation of trichloroacetic acid solution: take by weighing trichloroacetic acid 5g fast, use a spot of dissolved in distilled water, move in the 100mL volumetric flask, standardize solution is made into 5% trichloroacetic acid solution.

(3) drawing standard curve: the accurate 100mg/L glucose solution 0.05,0.10,0.20,0.30 of drawing, 0.40,0.60,0.80 (mL), put into test tube with ground stopper, supply 1.00mL, prepare a test tube that the 1.00mL distilled water is housed simultaneously and make blank pipe with distilled water.Add the 4.00mL anthrone reagent fast, and even with the agitator quick oscillation, immerse in the ice-water bath rapidly and cool off, treat that all test tubes all add, after test tube is cold slightly, put into boiling water bath together, pick up counting from the water-bath boiling, after boiling 10min, take out immediately, under flowing water, rapidly after cold, under room temperature, leave standstill about 10min, be the OD value that the 620nm place measures variable concentrations at wavelength again, plot standard curve.

(4) sample liver glycogen Determination on content: the liver that accurately takes by weighing about 20-30mg, put into glass homogenizer, add 4.00mL5% trichloroacetic acid solution, make homogenate, again with behind the centrifugal 10min of 8000rpm, accurately draw supernatant 1.00mL, add the 4.00mL anthrone reagent rapidly, other conditions are identical with step (3) operation.With regression equation calculation sample total sugar content, be converted into liver glycogen content (mg/g tissue wet) according to the liver weight that is taken by weighing.

(5) standard curve:

Measure the absorbance (A) of variable concentrations (C) glucose solution, the data drawing standard curve according to gained sees Table 18.

Table 18 standard curve data

Regression equation: A=6.4694C-0.004 R ²=0.9949

(6) calculating of hepatic glycogen content

Converting according to C/W (mg/g) to draw the content of hepatic glycogen, and W is the weight (mg) of the hepatic tissue got, the results are shown in Table 19.

Glycogen content in the table 19 normal mouse murine liver tissue (x ± SD)

Annotate: with normal control group ratio ^*P＜0.05 ^*P＜0.01

Each dosage group of medicament composition capsule of the present invention as can be known from the above table all can significantly increase the hepatic glycogen content (P＜0.01, P＜0.05) of normal mouse.

Experimental example 23 to experimental example 24 all adopts following test material and experimental technique:

The healthy Di Fake kind of laboratory animal Carnis Coturnicis japonicae, male 8 ages in week, body weight 140g-180g, De Ling Carnis Coturnicis japonicae plant provides by Beijing.Raise in the zoopery of 18～22 ℃ of cleaning levels indoor.

Positive control drug: XUEZHIKANG JIAONANG, Beijing University's dimension letter bio tech ltd provides; Lot number: 20060508, the Carnis Coturnicis japonicae consumption is 0.200g/kg.Compound method: take out capsule 's content, be mixed with solution with deionized water.

Main agents

Triglyceride test kit (lot number 071291) Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.

T-CHOL test kit (lot number 070371) Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.

HDL-C test kit (lot number 070141) Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.

Low-density lipoprotein cholesterol test kit (lot number 060131) Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.

(lot number: 20070620) bio-engineering research institute is built up in Nanjing to free fatty (NEFA) testing cassete

Cholesterol (BR, lot number: 20070315) the extensive and profound in meaning star biotechnology in Beijing responsibility company limited

The commercially available converted products of Adeps Sus domestica

Healthy male Di Fake kind Carnis Coturnicis japonicae is got in the foundation of experimental technique model, body weight 140g-180g, adaptability feed 1 week the back be divided into 2 groups on normal control and model at random by body weight.Normal control group feed normal diet, model group feed high lipid food (prescription: 1.0% cholesterol, 20% Adeps Sus domestica, 79% normal feedstuff) gives 15g every every day, and deficiency is then replenished normal diet, continuous 4 weeks.After 4 weeks, model group animal fasting (can't help water) 12h, right external jugular vein is got blood, from going out serum, measures cholesterol value, and according to cholesterol levels, selecting to have the Carnis Coturnicis japonicae of significant difference with the normal control group is that successful model is included experiment in.Select standard compliant model group Carnis Coturnicis japonicae,, adopt randomized blocks to be divided into 5 groups: model group, positive drug Xuezhikang group, the basic, normal, high dosage group of pharmaceutical composition of the present invention according to cholesterol levels.

The grouping administration keeps 15 Carnis Coturnicis japonicaes of normal control group.Select 64 of standard compliant model group Carnis Coturnicis japonicaes,, adopt randomized blocks to be divided into 5 groups according to serum cholesterol value.(1) the normal control group is 15: irritate stomach with the volume distilled water; (2) model control group is 15: irritate stomach with the volume distilled water; (3) positive drug Xuezhikang group is 13: irritate stomach Xuezhikang solution, every day, dosage was 200mgkg ^-1(4) medicament composition capsule high dose group of the present invention is 12: irritate stomach medicament composition capsule high dose of the present invention solution, every day, dosage was 6.04gkg ^-1(be equivalent to the clinical consumption of people 20 times); (5) 12 of dosage groups in the medicament composition capsule of the present invention: irritate dosage solution in the stomach medicament composition capsule of the present invention, every day, dosage was 3.02gkg ^-1(be equivalent to the clinical consumption of people 10 times); (6) medicament composition capsule low dose group of the present invention is 12: gavage medicament composition capsule low dosage solution of the present invention, every day, dosage was 1.51gkg ^-1(be equivalent to the clinical consumption of people 5 times).Each is organized and irritates stomach every day 1 time, and continuous 30 days, each medication volume was irritated stomach 1.0mL by every 100g body weight and calculated.Normal control group Carnis Coturnicis japonicae is raised with normal diet during the medication treatment, and other groups are raised with high lipid food (give 15g every every day, deficiency is then replenished normal diet), ad lib, drinking-water.

Preparation of specimen

Being prepared in during modeling and the medication treatment of blood sample, 1 right external jugular vein blood sampling weekly, monitoring blood fat four indices changes.Medication was treated the 30th day, fasting (can't help water) 12h, right external jugular vein blood-letting, inject a clean tube and leave standstill, separation of serum detects TG, TC, HDL-C, LDL-C, all the other blood serum samples are sub-packed in the frozen pipe of 1.5mL ,-20 ℃ of cold storage of refrigerator related biochemical indicator to be checked.

The preparation of tissue samples is cutd open rapidly and is got liver, thoracic aorta portion of tissue after putting to death Carnis Coturnicis japonicae, be soaked in fix in 10% formalin to be checked.

Observation index and detection method

TC, TG measure: adopt enzymic colorimetric.

HDL-C measures: adopt phosphotungstic acid-magnesium precipitate method.

LDL-C measures: adopt the polyvinyl sulfuric acid sedimentation method.

The free-fat acidity test:

Calculate atherogenic index: AI=(TC-HDL-C)/HDL-C

Calculate the liver coefficient: the 100g body weight contains liver and heavily restrains numerical value.

Statistical method

(x ± s) expression adopts the SPSS12.0 statistical software to experimental data, and relatively, significance level was a standard with 0.05 and 0.01 between utilization one factor analysis of variance (one-way ANOVA) carried out respectively organizing with mean ± standard deviation.

Experimental example 23 medicament composition capsules of the present invention are to the lipometabolic influence of bait hypercholesterolemia Carnis Coturnicis japonicae

1, the lipid metabolism variation sees Table 20 during the modeling:

The variation of Carnis Coturnicis japonicae serum TC, TG after 2 weeks of table 20 modeling (x ± s)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

During the modeling, in normal group Carnis Coturnicis japonicae normal diet 4 weeks of feed, body weight steadily increases to 163.85 ± 14.36g by 142.84 ± 13.61g.In model group Carnis Coturnicis japonicae high lipid food 4 weeks of feed, body weight is rapidly increased to 179.00 ± 20.16g by 138.86 ± 17.62g, is significantly higher than normal control group (P＜0.01).

Serum biochemistry is learned testing result and shown: modeling is during 2 weeks, and model group is compared cholesterol levels and obviously raise (P＜0.01) with the blank group, but triglyceride there was no significant difference (P＞0.05).

Modeling 4 is during week, and model group serum TC, TG, LDL-C, HDL-C level further raise, and compares with the blank group that there were significant differences (P＜0.01), and atherogenic index significantly raises (P＜0.01), sees Table 21.

Table 21 modeling 4 week back Carnis Coturnicis japonicae serum TCs, TG, LDL-C, HDL-C, atherogenic index AI (x ± s)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

2, medicament composition capsule of the present invention sees Table 22 to the lipometabolic influence of bait hypercholesterolemia Carnis Coturnicis japonicae:

Table 22 medicament composition capsule of the present invention is to the influence of bait hypercholesterolemia Carnis Coturnicis japonicae serum TC (x ± s)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01 is with normal control group ratio ^#P＜0.05 ^##P＜0.01

The result shows that the high lipid food feed is after 4 weeks, and model group compares serum TC with blank group and obviously raises, and there were significant differences (P＜0.01); And other each administration groups are compared zero difference with model group.After 2 weeks of administration, positive drug Xuezhikang group, pharmaceutical composition low dose group TC of the present invention descend to some extent than model group, but zero difference (P＞0.05); Drug regimen object height of the present invention, middle dosage group are compared obvious decline (P＜0.01, P＜0.05) with model group.After 4 weeks of administration, each administration group serum TC all has significant decline (P＜0.01) than model group.

Table 23 medicament composition capsule of the present invention is to the influence of bait hypercholesterolemia Carnis Coturnicis japonicae serum TG (x ± s)

The result shows that the high lipid food feed is after 4 weeks, and model group compares serum TG with blank group and obviously raises, and there were significant differences (P＜0.01); And other each administration groups are compared zero difference with model group.After 2 weeks of administration, positive drug Xuezhikang group, each dosage group TG of pharmaceutical composition of the present invention all descend to some extent than model group, and there were significant differences (P＜0.01, P＜0.05), wherein positive drug and blank group zero difference; After 4 weeks of administration, each administration group serum TG all has significant decline (P＜0.01, P＜0.05) than model group, and with blank group zero difference.(seeing Table 23)

Table 24 medicament composition capsule of the present invention is to the influence of bait hypercholesterolemia Carnis Coturnicis japonicae serum LDL-C (x ± s)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

Table 25 medicament composition capsule of the present invention is to the influence of bait hypercholesterolemia Carnis Coturnicis japonicae Serum HDL-C (x ± s)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

Table 26 medicament composition capsule of the present invention is to the influence of bait hypercholesterolemia Carnis Coturnicis japonicae atherogenic index AI (x ± s)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

Table 27 medicament composition capsule of the present invention is to the influence of administration 4 all back bait hypercholesterolemia Carnis Coturnicis japonicae body weight and liver coefficient

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

Table 28 medicament composition capsule of the present invention is to the influence of administration 4 week back bait hypercholesterolemia Carnis Coturnicis japonicae free serum fatty acids (NEFA)

Annotate: with the model group ratio ^*P＜0.05 ^*P＜0.01

Conclusion: in the bait hypercholesterolemia Carnis Coturnicis japonicae lipid metabolism test, modeling is during 4 weeks, and model group serum TC, TG, LDL-C, HDL-C level raise, and compares with the blank group that there were significant differences (P＜0.01), and atherogenic index significantly raise (P＜0.01).Show the success of hypercholesterolemia Carnis Coturnicis japonicae model.After 4 weeks of administration, the peaceful high, medium and low dosage group of the bent glycolipid of stilbene (crude drug dosage is 6.04,3.02,1.56g/kg, extractum dosage is 1.32,0.66,0.33g/kg) serum TC, TG, LDL-C all have significant decline (P＜0.01) than model group.Peaceful each the dosage group of the bent glycolipid of stilbene all can significantly reduce atherogenic index (P＜0.01); Peaceful each the dosage group of the bent glycolipid of stilbene all can significantly reduce free serum content of fatty acid and liver coefficient (P＜0.01).The result shows that the bent glycolipid of stilbene rather can be regulated the disorders of lipid metabolism of hypercholesterolemia Carnis Coturnicis japonicae, reduces the arteriosclerosis degree.

Following embodiment all can realize the effect of above-mentioned experimental example.

The specific embodiment

Embodiment 1: the preparation of capsule

Radix Astragali 555g Folium Mori 555g Radix Puerariae 278g Rhizoma Alismatis 555g Monas cuspurpureus Went 66.6g

Get the Radix Astragali, add 70% soak with ethanol 2 hours, reflux, extract, 2 times, add for the first time 7 times of amounts of Radix Astragali ethanol, extracted 1 hour, add 6 times of amounts of Radix Astragali ethanol for the second time, extracted 1 hour, and filtered, filtrate merges, vacuum≤-0.05Mpa, ethanol is reclaimed in temperature≤70 ℃, and vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, and temperature≤70 ℃ drying under reduced pressure, get pure promotion cream A, standby; Astragalus root dregs and Folium Mori were soaked 2 hours, decocted with water 2 times, add astragalus root dregs and 12 times of water gagings of Folium Mori for the first time, decocted 1 hour, and added astragalus root dregs and 10 times of water gagings of Folium Mori for the second time, decocted 1 hour, filter, collecting decoction, vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets the dried cream B of decocting in water, and is standby; Get Radix Puerariae, Rhizoma Alismatis and added 70% soak with ethanol 16 hours, reflux, extract, 2 times adds 6 times of amounts of Radix Puerariae and Rhizoma Alismatis ethanol for the first time, extracted 1 hour, and added 5 times of amounts of Radix Puerariae and Rhizoma Alismatis ethanol for the second time, extracted 1 hour, filter, filtrate merges, vacuum≤-0.05Mpa, 70 ℃ of temperature reclaim ethanol, and vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets pure promotion cream C, and is standby; Above alcohol promotion cream A and C, the dried cream B of decocting in water are pulverized, cross 80 mesh sieves, mix, standby; Get Monas cuspurpureus Went, microcrystalline Cellulose and said extracted thing mixed powder mix homogeneously, wherein the weight of microcrystalline Cellulose accounts for 10.4% of finished product gross weight, granulates, and crosses 30 mesh sieve granulate, the magnesium stearate that adds finished product gross weight 2% again, mixing incapsulates, make 1000, each 3, every day 3 times.

Embodiment 2: tablet

Radix Astragali 650g Folium Mori 450g Radix Puerariae 230g Rhizoma Alismatis 650g Monas cuspurpureus Went 90g

Get the Radix Astragali, add 70% soak with ethanol 2 hours, reflux, extract, 2 times, add for the first time 7 times of amounts of Radix Astragali ethanol, extracted 1 hour, add 6 times of amounts of Radix Astragali ethanol for the second time, extracted 1 hour, and filtered, filtrate merges, vacuum≤-0.05Mpa, ethanol is reclaimed in temperature≤70 ℃, and vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, and temperature≤70 ℃ drying under reduced pressure, get pure promotion cream A, standby; Astragalus root dregs and Folium Mori were soaked 2 hours, decocted with water 2 times, add astragalus root dregs and 12 times of water gagings of Folium Mori for the first time, decocted 1 hour, and added astragalus root dregs and 10 times of water gagings of Folium Mori for the second time, decocted 1 hour, filter, collecting decoction, vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets the dried cream B of decocting in water, and is standby; Get Radix Puerariae, Rhizoma Alismatis and added 70% soak with ethanol 16 hours, reflux, extract, 2 times adds 6 times of amounts of Radix Puerariae and Rhizoma Alismatis ethanol for the first time, extracted 1 hour, and added 5 times of amounts of Radix Puerariae and Rhizoma Alismatis ethanol for the second time, extracted 1 hour, filter, filtrate merges, vacuum≤-0.05Mpa, 70 ℃ of temperature reclaim ethanol, and vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets pure promotion cream C, and is standby; Above alcohol promotion cream A and C, the dried cream B of decocting in water are pulverized, cross 80 mesh sieves, mix, standby; Get Monas cuspurpureus Went, microcrystalline Cellulose and said extracted thing mixed powder mix homogeneously, wherein the weight of microcrystalline Cellulose accounts for 10.4% of finished product gross weight, granulates, and crosses 30 mesh sieve granulate, the magnesium stearate that adds finished product gross weight 2% again, mixing, tabletting, make 1000, each 3, every day 3 times.

Embodiment 3: the preparation of granule

Radix Astragali 450g Folium Mori 750g Radix Puerariae 310g Rhizoma Alismatis 450g Monas cuspurpureus Went 30g

Get above-mentioned five tastes medical material,, add conventional adjuvant, make granule according to conventional method.

Embodiment 4: the preparation of pill

Get above-mentioned five tastes medical material,, add conventional adjuvant, make pill according to conventional method.

Embodiment 5: the preparation of soft extract with bee honey agent

Get above-mentioned five tastes medical material,, add conventional adjuvant, make the soft extract with bee honey agent according to conventional method.

Embodiment 6: the preparation of oral liquid

Get above-mentioned five tastes medical material,, add conventional adjuvant, make oral liquid according to conventional method.

Embodiment 7: the preparation of ejection preparation

Get above-mentioned five tastes medical material,, add conventional adjuvant, make ejection preparation according to conventional method.

Claims

1. pharmaceutical composition for the treatment of diabetes and/or hyperlipidemia is characterized in that the raw material of this pharmaceutical composition

Medicine consists of:

2. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:

3. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:

4. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:

5. as the arbitrary described pharmaceutical composition of claim 1-4, it is characterized in that getting this pharmaceutical composition crude drug, add conventional adjuvant,, make tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid or ejection preparation according to common process.

6. pharmaceutical composition as claimed in claim 5 is characterized in that described capsule is a soft capsule, and described pill is drop pill or honeyed pill.

7. as the arbitrary described pharmaceutical composition of claim 1-4, it is characterized in that getting this pharmaceutical composition crude drug, add conventional adjuvant,, make controlled release preparation according to common process.

8. pharmaceutical composition as claimed in claim 7 is characterized in that described controlled release preparation is slow releasing preparation or quick releasing formulation.

9. as the arbitrary described preparation of drug combination method of claim 1-4, it is characterized in that this method comprises the steps:

Get the Radix Astragali. added the 60%-80% soak with ethanol 1-3 hour, reflux, extract, 2 times, for the first time add Radix Astragali 5-10 and doubly measure ethanol, extracted 0.5-2 hour, add Radix Astragali 4-8 for the second time and doubly measure ethanol, extracted 0.5-2 hour, and filtered, filtrate merges, vacuum≤-0.05Mpa, temperature 60-90 ℃ is reclaimed ethanol, and vacuum≤-0.06Mpa, temperature 60-90 ℃ is concentrated into the thick paste that relative density is 1.05-1.50, vacuum≤-0.06Mpa, temperature 60-90 ℃ of drying under reduced pressure, get pure promotion cream A, standby; Astragalus root dregs and Folium Mori were soaked 1-3 hour, decocted with water 2 times, add astragalus root dregs and Folium Mori 10-14 times water gaging for the first time, decocted 0.5-2 hour, and added astragalus root dregs and Folium Mori 8-12 times water gaging for the second time, decocted 0.5-2 hour, filter, collecting decoction, vacuum≤-0.06Mpa, temperature 60-90 ℃ is concentrated into the thick paste that relative density is 1.05-1.50, vacuum≤-0.06Mpa, temperature 60-90 ℃ of drying under reduced pressure gets the dried cream B of decocting in water, and be standby; Get Radix Puerariae, Rhizoma Alismatis and add soak with ethanol 14-18 hour of 60%-80%, reflux, extract, 2 times, the first time adds Radix Puerariae and Rhizoma Alismatis 4-8 doubly measures ethanol, extracted 0.5-2 hour, the second time adds Radix Puerariae and Rhizoma Alismatis 4-8 doubly measures ethanol, extracted 0.5-2 hour, and filtered, filtrate merges, vacuum≤-0.05Mpa, temperature 60-90 ℃ is reclaimed ethanol, and vacuum≤-0.06Mpa, temperature 60-90 ℃ is concentrated into relative density is 1.05～1.50 thick paste, vacuum≤-0.06Mpa, temperature 60-90 ℃ of drying under reduced pressure gets pure promotion cream C, and be standby; Above alcohol promotion cream A and C, the dried cream B of decocting in water are pulverized, cross 80 mesh sieves, mix, standby; Get Monas cuspurpureus Went, microcrystalline Cellulose and said extracted thing mixed powder mix homogeneously, wherein the weight of microcrystalline Cellulose accounts for the 8%-18% of finished product gross weight, granulate, cross 30 mesh sieve granulate, the magnesium stearate that adds finished product gross weight 0.5%-3% again, mixing adds conventional adjuvant according to a conventional method and makes tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation or oral liquid.

10. preparation of drug combination method as claimed in claim 9, it is characterized in that this method comprises the steps: to get the Radix Astragali, add 70% soak with ethanol 2 hours, reflux, extract, 2 times adds 7 times of amounts of Radix Astragali ethanol for the first time, extracts 1 hour, add for the second time 6 times of amounts of Radix Astragali ethanol, extracted 1 hour, and filtered, filtrate merges, vacuum≤-0.05Mpa, ethanol is reclaimed in temperature≤70 ℃, and vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets pure promotion cream A, and is standby; Astragalus root dregs and Folium Mori were soaked 2 hours, decocted with water 2 times, add astragalus root dregs and 12 times of water gagings of Folium Mori for the first time, decocted 1 hour, and added astragalus root dregs and 10 times of water gagings of Folium Mori for the second time, decocted 1 hour, filter, collecting decoction, vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets the dried cream B of decocting in water, and is standby; Get Radix Puerariae, Rhizoma Alismatis and added 70% soak with ethanol 16 hours, reflux, extract, 2 times adds 6 times of amounts of Radix Puerariae and Rhizoma Alismatis ethanol for the first time, extracted 1 hour, and added 5 times of amounts of Radix Puerariae and Rhizoma Alismatis ethanol for the second time, extracted 1 hour, filter, filtrate merges, vacuum≤-0.05Mpa, 70 ℃ of temperature reclaim ethanol, and vacuum≤-0.06Mpa, it is 1.25～1.30 thick paste that temperature≤70 ℃ are concentrated into relative density, at vacuum≤0.06Mpa, temperature≤70 ℃ drying under reduced pressure gets pure promotion cream C, and is standby; Above alcohol promotion cream A and C, the dried cream B of decocting in water are pulverized, cross 80 mesh sieves, mix, standby; Get Monas cuspurpureus Went, microcrystalline Cellulose and said extracted thing mixed powder mix homogeneously, wherein the weight of microcrystalline Cellulose accounts for 10.4% of finished product gross weight, granulate, cross 30 mesh sieve granulate, the magnesium stearate that adds finished product gross weight 2% again, mixing adds conventional adjuvant according to a conventional method and makes tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation or oral liquid.

11. as the application of the arbitrary described pharmaceutical composition of claim 1-4 in the medicine of preparation treatment diabetes and/or hyperlipidemia.