CN101472600A

CN101472600A - Medicament composition for regulating blood sugar and blood fat as well as preparation method and application thereof

Info

Publication number: CN101472600A
Application number: CNA2007800146228A
Authority: CN
Inventors: 魏子孝; 刘建勋; 郭宇洁; 葛争艳
Original assignee: Xiyuan Hospital China Academy Of Chinese Medical Sciences
Current assignee: Xiyuan Hospital China Academy Of Chinese Medical Sciences
Priority date: 2007-07-31
Filing date: 2007-07-31
Publication date: 2009-07-01
Anticipated expiration: 2027-07-31
Also published as: CN101472600B; WO2009015515A1; AU2007357043B2; AU2007357043A1

Abstract

A pharmaceutical composition for regulating blood sugar level and blood fat level, process for preparation and use thereof. The pharmaceutical composition comprises the following Chinese medicinal materials or extracts thereof in weight portions: Fructus ligustri 5-17, Radix astragali 3-12, Rhizoma coptidis 1-5, Semen litchi 1-5, and, optionally, Herba laminariae 1-6 and/or Radices curcumae 1-6. The pharmaceutical composition of the present invention can be used to treat or prevent diabetes and complications thereof.

Description

Medicament composition for regulating blood sugar and blood fat as well as preparation method and application thereof

A kind of regulation blood glucose, the pharmaceutical composition of blood fat and its production and use technical field

The present invention relates to a kind of pharmaceutical composition for adjusting blood glucose, blood fat, more particularly to the pharmaceutical composition by being prepared from as the Chinese medicine of active component or its extract, and prepare the method and its purposes for being used to treat diabetes and its complication of the pharmaceutical composition.Background technology

Diabetes are a kind of common endocrine metabolism diseases, and its distribution time is in the trend gradually increased in the whole world.The illness rate of China's diabetes is up to 15 %., possessed second largest diabetic population in the world, and just increasing with every speed doubled for 15 years.In diabetes patient groups based on type ii diabetes.Insulin resistance（The insulin of normal dose produces a kind of state less than natural biological effect）After generation, as long as pancreas can maintain sufficiently high amount of insulin secretion to overcome insulin resistance, then sugar tolerance will keep normal or only slight impaired.Once p cell functions start exhaustion, sugar tolerance will deteriorate rapidly, would develop into diabetes.Insulin resistance is the major reason of the morbidity of type ii diabetes, and fat metabolic disturbance is often accompanied by while carbohydrate metabolism disturbance, therefore improves insulin resistance, controls sugared fat metabolic disturbance, treat complication is the emphasis for the treatment of diabetes.

Existing Chinese medicine preparation majority using supplementing qi and nourishing yin, activating blood and removing stasis Method as principle, hypoglycemic effect is more obvious in being treated to type ii diabetes, but reduction blood fat, correct diabetic fatty metabolic disorder it is not notable.Supplementing qi and nourishing yin, the less application in type ii diabetes treatment of eleminating phlegm and freeing channels method, but the method is while blood glucose is reduced, and has good therapeutic effect to adjustment diabetic fatty metabolic disorder.The content of the invention

An object of the present invention is to provide a kind of new regulation blood glucose, the pharmaceutical composition of blood fat. It is a further object of the present invention to provide a kind of method for preparing pharmaceutical composition of the present invention.Another object of the present invention is to provide a kind of method of medicine composite for curing diabetes using the present invention and its complication, or the pharmaceutical composition of the present invention is preparing the purposes in being used to treat the medicine of diabetes and its complication.

To achieve the above object, present inventor has found by long-term further investigation, using supplementing qi and nourishing yin, eleminating phlegm and freeing channels as the principles of formulating prescriptions, can provide a kind of can adjust blood glucose, blood fat and improve insulin resistance, the medicine that diabetes and its complication occur effectively prevented and treated, it is achieved thereby that above-mentioned purpose.

On the one hand, the present invention provides a kind of regulation blood glucose, the pharmaceutical composition of blood fat, and it is made up of the Chinese medicine or its extract of following parts by weight:Fruit of glossy privet 5-17, Radix Astragali 3-12, coptis 1-5, semen litchi 1-5, cloth 1-6 and turmeric 1-6.

Preferably, the present invention provides a kind of regulation blood glucose, the pharmaceutical composition of blood fat, and it is made up of the Chinese medicine or its extract of following parts by weight：Fruit of glossy privet 8-15, Radix Astragali 4-10, coptis 2-3, semen litchi 3-4, kelp 3-5 and turmeric 3-5.

Most preferably, the present invention provides a kind of regulation blood glucose, the pharmaceutical composition of blood fat, and it is made up of the Chinese medicine or its extract of following parts by weight：The fruit of glossy privet 8, the Radix Astragali 4, the coptis 2, semen litchi 4, kelp 3 and turmeric 3.

According to the pharmaceutical composition of the present invention, Chinese medicine therein can be replaced with their solvent extractable matter, active component or active ingredient respectively.Wherein described extract is alcohol extracting thing, 7 extracts or volatile oil.Thing for example can be taken comprising fruit of glossy privet alcohol extracting thing, coptis alcohol extracting thing, Radix Astragali alcohol extracting thing, turmeric volatile-oil, turmeric water extract, semen litchi water extract and the kelp for treating or improving diabetes and its complication effective dose according to the pharmaceutical composition of the present invention.

According to the pharmaceutical composition of the present invention, it can also include pharmaceutically acceptable any auxiliary material, such as dextrin, preferably times his dextrin.

According to the pharmaceutical composition of the present invention, Chinese medicine component therein can be replaced or increase and decrease according to traditional Chinese medical theory, and the content of each component can also change.Such as kelp therein Can be without, or replaced it with sea-tangle or marine alga；Turmeric can be without, or is replaced it with root tuber of aromatic turmeric or curcuma zedoary.

Therefore, the present invention also provides the pharmaceutical composition for adjusting blood glucose, blood fat, and it includes the Chinese medicine or its extract of following parts by weight：Fruit of glossy privet 5-17, Radix Astragali 3-12, coptis 1-5 and semen litchi 1-5, and pharmaceutically acceptable auxiliary material.

According to the pharmaceutical composition of the present invention, it can be prepared to formulation commonly used in the art, such as tablet, granule or glue Nang together with pharmaceutically acceptable any auxiliary material.Their mixture can also be directly used, or uses each component or the solvent extractable matter of mixture.

According to the pharmaceutical composition of the present invention, when using the photograph thin-layered chromatography described in one annex VIB of China's coastal port and when being detected respectively using oleanolic acid, Berberine hydrochloride, Radix Astragali Yue glycosides and protocatechuic acid as reference substance, the pharmaceutical composition manifests the spot of same color on the corresponding position of the reference substance.It is specific to differentiate as follows.

(1) the pharmaceutical composition 2g of the present invention, plus absolute ethyl alcohol 5ml are taken, ultrasonically treated 25 minutes, is let cool, is filtered, filtrate is used as need testing solution.Separately take oleanolic acid reference substance, plus absolute ethyl alcohol that solution of every lml containing 0.5mg is made, be used as reference substance solution.According to thin-layered chromatography（Annex VIB) experiment, draw the above-mentioned μ 1 of need testing solution 5, the μ 1 of reference substance solution 10, put respectively in it is same using carboxylic Yue bases sodium cellulosate as the silica gel g thin-layer plate of binder on, with petroleum ether-acetone-methanol（8: 2:0.3) it is solvent, deploys, take out, dry, sprays with 10% ethanol solution of sulfuric acid, 80.It is clear that C is heated to spot development.In test sample chromatogram, on position corresponding with reference substance chromatogram, show the spot of same color.

(2) the pharmaceutical composition 0.5g of the present invention, plus methanol 5ml are taken, ultrasonically treated 30 minutes, is let cool, is filtered, filtrate, which adds Yue alcohol, makes into 5ml, is used as need testing solution.Separately take Berberine hydrochloride reference substance, plus Yue alcohol that solution of every lml containing O.lmg is made, be used as reference substance solution.According to thin-layered chromatography（Annex IB) experiment, the above-mentioned μ 1 of need testing solution 2, the μ 1 of reference substance solution 2 are drawn, is put respectively on the same silica G lamellae using sodium carboxymethylcellulose as binder, with benzene-ethyl acetate-isopropanol-methanol-water（6: 3: 1.5: 1.5: 0.3 ) For solvent, in the expansion cylinder for putting ammonia saturated with vapor, deploy, take out, dry, put ultraviolet lamp（Inspected under 365nm).In test sample chromatogram, on position corresponding with reference substance chromatogram, show the fluorescence spot of same color.

(3) the pharmaceutical composition 6g of the present invention, plus 2% sodium hydroxide Yue alcoholic solution 20ml are taken, is heated to reflux 40 minutes, lets cool, is filtered, filtrate is evaporated, the residue 30ml that adds water makes dissolving, is extracted 3 times with water saturated n-butanol（30ml, 20ml, 20ml), merge n-butanol liquid；It is washed with water 2 times, every time 20 ml;Aqueous is discarded, then is washed 1 time with 1% di(2-ethylhexyl)phosphate hydrogen clock solution, aqueous is discarded, n-butanol liquid is evaporated, and residue adds methanol 5ml to make dissolving, is used as need testing solution.Separately take Astragaloside IV reference substance, plus methanol that solution of every lml containing 0.3mg is made, be used as reference substance solution.According to thin-layered chromatography（Annex IB) experiment, draw the above-mentioned μ 1 of need testing solution 10 ~ 15, reference substance solution Ι Ο μ Ι, put respectively in it is same using sodium carboxymethylcellulose as the silica gel g thin-layer plate of binder on, with chloroform-methanol-water (20: 7:2) lower floor's solution is solvent, is deployed, and takes out, dries, and is sprayed with 10% ethanol solution of sulfuric acid, 80.It is clear that C is heated to spot development.In test sample chromatogram, on position corresponding with reference substance color language, show the spot of same color.

(4) the pharmaceutical composition 3g of the present invention is taken, add water 50 ml, is heated to reflux 1 hour, lets cool, filtration, filtrate adjusts PH=2 with 10% HCL, and acidifying solution is extracted three times with ether, each 15ml, combining extraction liquid, ether is reclaimed, residue adds Yue alcohol lml to make dissolving, is used as need testing solution.Separately take protocatechuic acid reference substance, plus methanol that solution of every lml containing 0.2mg is made, be used as reference substance solution.According to thin-layered chromatography（Annex VIB) experiment, the above-mentioned μ 1 of need testing solution 10, the μ 1 of reference substance solution 8 are drawn, is put respectively in the same silica gel using sodium carboxymethylcellulose as adhesive（F₂₅₄On lamellae, with Yue benzene-ethyl acetate-Yue acid（12: 6:1) it is solvent, deploys, takes out, dry, put ultraviolet lamp（Inspected under 254nm).During test sample color is known well, said with reference substance color on corresponding position, show the spot of same color.

According to the pharmaceutical composition of the present invention, when using the high performance liquid chromatography described in one annex VI D of China's coastal port and when being detected using oleanolic acid and ursolic acid as reference substance, the content of oleanolic acid and ursolic acid in pharmaceutical composition is no less than 4.0 mg Specifically it is determined as follows with 1.0 mgo.

It is filler with octadecylsilane chemically bonded silica；The % phosphoric acid waters of Yue alcohol -0.05（90:10) it is mobile phase；Detection wavelength is 215nm.Theoretical cam curve is calculated by oleanolic acid should be not less than 3000.Precision weighs oleanolic acid, ursolic acid reference substance in right amount, plus every lml is made containing neat ^ t tartaric acid 0.20mg, ursolic acid 0.15mg solution in acetonitrile, produces reference substance solution.The lower content of this product content uniformity is taken, it is finely ground, 0.8g is taken, it is accurately weighed, Yue alcohol 20ml are added, is heated to reflux 45 minutes, lets cool, be transferred in 50ml measuring bottles, with a small amount of Yue alcohol gradation washing container and residue, washing lotion is transferred in same measuring bottle, shaken up, and uses miillpore filter（0.45um) filter, take subsequent filtrate, produce need testing solution.It is accurate respectively to draw the above-mentioned μ 1 of reference substance solution 15, the μ 1 of need testing solution 10, liquid chromatograph is injected, is determined, pharmaceutical composition of the invention contains oleanolic acid（C₃₍₎H₄₈0₃) 4.0m must not be less than_g。

On the other hand, the present invention provides a kind of method for the pharmaceutical composition for preparing the present invention, and this method comprises the following steps：

The fruit of glossy privet is heated to reflux with ethanol, is extracted multiple, is merged alcohol extract, reclaims alcohol, extract drying for standby；

Turmeric is extracted with steam distillation, collects volatile oil, the aqueous solution and the dregs of a decoction are standby；Gained volatile oil cyclodextrin and water inclusion, are stirred, and are refrigerated, filtration, and gained inclusion complex low temperature drying is crushed, standby；

With decocting repeatedly, collecting decoction, filtration, filtrate merges with the above-mentioned turmeric aqueous solution for semen litchi, kelp, concentrates, plus alcohol, refrigerates, and filtration obtains water decoction-alcohol sedimentation liquid standby；And

The coptis, the Radix Astragali are heated to reflux with the above-mentioned turmeric dregs of a decoction with alcohol, extract multiple, merge alcohol extract and merge with above-mentioned water decoction-alcohol sedimentation liquid, reclaim alcohol, dry and mixed with above-mentioned fruit of glossy privet alcohol extracting thing, turmeric cyclodextrin inclusion complex fine powder, when needing again with pharmaceutically acceptable auxiliary materials and mixing, required formulation is made.

Preparation in accordance with the present invention, its processing step and condition can be optimized according to following experimental result. 1. turmeric volatile-oil extracts preferred with inclusion condition

1.1. influence and the determination of volatile oil extracting time of the degree of grinding to turmeric volatile-oil extracted amount

Weigh two parts of turmeric, every part of 100g, two parts of specification is respectively medicine materical crude slice, 10 mesh, is separately added into 10 times of amount water, and steam distillation extracts volatile oil, the results are shown in Table 1.The turmeric volatile-oil extraction time of table 1. and the investigation extraction time of degree of grinding（Hour) 123456789 medicine materical crude slice oil pump capacity (ml) 0.4 0.8 1.0 1.2 1.4 1.5 1.6 1.95 2.0

10 mesh oil yields（%) 1.4 2.2 3.1 3.6 3.8 4.1 4.4 4.6 4,7 result above show that influence of the degree of grinding to turmeric volatile-oil extracted amount is larger, so needing appropriate crush during turmeric volatile-oil extraction, in order to ensure Non-burnt pot in process of production, the selection of turmeric degree of grinding is 10 mesh.10 mesh turmeric volatile-oils extract 9 hours fuel-displaced 4.7ml, extract 8 hours it is fuel-displaced 4.6 hours, the oil yield of 8 hours reaches 97%, thus determine turmeric volatile-oil extraction time be 8 hours.

1.2. the influence to volatile oil extracting amount is soaked

Two parts of turmeric is weighed, every part of 100g, a copy of it does not soak direct extraction, another immersion is extracted after 2 hours, the results are shown in Table 2.Table 2. soaks the influence extraction time extracted to turmeric volatile-oil（Hour）12345678 immersions（Ml) 0.4 1.4 1.9 2.2 2.6 2.8 3.2 3.4 do not soak (ml) 1.4 2.2 3.1 3.6 3.8 4.1 4.4 4.6 result above and show, influence to turmeric volatile-oil extracted amount are soaked less, so 10 Mesh turmeric need not be soaked during volatile oil extracting.

2. the influence that amount of water is extracted to Herba Asari volatile oil

The influence extraction time that the amount of water of table 3. is extracted to Herba Asari volatile oil（Hour） 1 2 3 4 5 6 7 8

8 times of amount water 1.4 1.9 2.3 2.7 3.3 3.6 3.9 4.1

10 times of amount water 1.4 2.2 3.1 3.6 3.8 4.1 4.4 4.6

12 times of amount result above of water 1.3 2.3 2.8 3.3 3.7 3.9 4.3 4.6 show, turmeric volatile-oil adds 10 times of amount water, than 8 times amount water oil pump capacity of 12 times of amount water high when extracting, and 10 times of amounts and 12 times of amounts are more or less the same, therefore selection amount of water is 10 times of amounts.

In summary, the optimum condition of turmeric volatile-oil extraction is：10 mesh turmerics add 10 times of amount water to extract volatile oil with steam distillation, and the volatile oil extracting time is 8 hours.

3. turmeric volatile-oil inclusion technique is preferred

Taking volatile oil to carry out inclusion, 70 with the betadex and 60 times of water measured of 6 times of amounts, " C is stirred 1 hour, refrigerated overnight, filtration, inclusion complex low temperature drying（40.C), fine powder is ground into, it is standby.

4. fruit of glossy privet alcohol extracting condition is preferred

Fruit of glossy privet 20g, totally 9 parts are weighed, alcohol extracting concentration, three factors of alcohol extracting multiple and alcohol extracting number of times are selected as the investigation factor of orthogonal test, each factor respectively takes three levels（It is shown in Table 4), each extraction time is 2 hours.Using L₉ ( 3⁴) orthogonal arrage tested, using Oleanolic Acid in Herbal Ligustrum lucidum, ursolic acid content as inspection target, factor level design is shown in Table orthogonal examination Xu of 4o and the results are shown in Table 5, and the result in table 5 is carried out after statistical procedures, analysis of variance table is seen（It is shown in Table 6,7). The alcohol extracting factor level table of table 4.

Horizontal A (alcohol extracting concentration %) B (plus alcohol multiple）C (alcohol extracting number of times）

1 55 4 1

2 75 5 2

3 95 63 tables 5, orthogonal test scheme and result

Ursolic acid in olive acidleach bone in experiment leaching bone

A B C D

Sequence number content (mg/g) content (mg/)

1 1 1 1 1 2.24 0.42

2 1 2 2 2 4.83 1.02

3 1 3 3 3 7.28 1.90

4 2 1 2 3 7.65 2.17

5 2 2 3 1 8.13 2.19

6 2 3 1 2 6.34 1.97

7 3 1 3 2 6.94 2.12

8 3 2 1 3 6.26 1.99

93321 7.26 2.58 neat K1 14.35 16.83 14.84 17.63

∑=56.93 of pier K2 22.12 19.22 19.74 18.11

CT=360.1138777 of fruit K3 20.46 20.88 22.35 21.19

Sour S 11.1623 2.7633556 9 691,355 6 2.4878223

Bear K1 3.34 4.71 4.38 5.19

∑=16.36 of fruit K2 6.33 5.2 5.77 5.11

Sour CT=29.73884444 of K3 6.69 6.45 6.21 6.06

S 2.25468889 0.53 668889 0.608 28889 0.18508889 The oleanolic acid analysis of variance table of table 6.

The source quadratic sum free degree side and F compare conspicuousness

A 11.1623 2 5.58115 4.4868

B 2.7633556 2 1.3816778 1.1108

C 9.6913556 2 4.8456778 3.8955

Error=D 2.4878223 2 1.24391115

The ursolic acid analysis of variance table of table 7.

Quadratic sum of the originating free degree side and F are than conspicuousness A 2.25468889 2 1.127344445 12.1817

B 0.53668889 2 0.268344445 2.8996

C 0.60828889 2 0.304144445 3.2865

Error=D 0.18508889 2 0.092544445

Fl-0.05 (2,2)=19 From above-mentioned variance analysis, three factors there are no significant difference.The extraction conditions for obtaining oleanolic acid by range analysis are A₂B₃C₃, the extraction conditions of ursolic acid are A₃B₃C₃, because determining alcohol influences on extracting no conspicuousness, select A₂The extraction of oleanolic acid is more beneficial for, therefore finally selects A₂B₃C₃, i.e. the optimum extraction condition of the fruit of glossy privet is：Extracted three times, every time 2 hours with 6 times of 75% ethanol of amount.

5. coptis astragalus alcohol extracting condition is preferred

5.1. coptis astragalus orthogonal test

Weigh coptis 15g, the Radix Astragali 30_g, totally 9 parts, alcohol extracting concentration plus three factors of alcohol multiple and alcohol extracting number of times are selected as the investigation factor of orthogonal test, each factor respectively takes three levels（It is shown in Table 4), each extraction time is 2 hours.Using L₉ ( 3⁴) orthogonal arrage tested, the content of Berberine hydrochloride is as inspection target using in the coptis, and factor level design is shown in Table 8.Orthogonal test and result table 9, carry out after statistical procedures to the result in table 9, see analysis of variance table (being shown in Table 10).The alcohol extracting factor level table of table 8.

1 30 4 1

2 50 5 2

The orthogonal test scheme of 3 70 63 table 9. and result

Test Berberine hydrochloride in medicinal extract

A B C D

Sequence number content (mg/g)

1 1 1 1 1 10.86

2 1 2 2 2 17.14

3 1 3 3 3 19.39

4 2 1 2 3 18.58

5 . 2 2 3 1 21.38

6 2 3 1 2 14.04

7 3 1 3 2 20.71

8 3 2 1 3 13.53

9 3 3 2 1 19.55

K1 47.39 50.15 38.43 51.79

K2 54.00 52.05 55.27 51.89 Σ-155.18

K3 53.79 52.98 61.48 51.50 CT-2675.648044

S 9.410689 1.387089 94.827889 0.027356 The Berberine hydrochloride analysis of variance table of table 10.

The source quadratic sum free degree side and F compare conspicuousness

A 9.410689 2 4.7053445 344.0082

B 1.387089 2 0.6935445 50.7051

C 94.827889 2 47.4139445 3466.4384

Error=D 0.027356 2 0.013678

Fl-0.10 (2,2)=19 From above-mentioned variance analysis, three factors have significant difference, A factors selection A₂, B factors selection B₃, C factors selection C₃, therefore the optimum extraction condition of Berberine hydrochloride is in coptis astragalus： A₂ B₃ C₃, i.e., extracted 3 times, every time 2 hours with the ethanol of 6 times of amounts 5 0%.

6. coptis astragalus orthogonal test is verified

In order to verify above-mentioned experimental condition, the coptis, the Radix Astragali are weighed, sample is prepared according to above-mentioned optimum extraction condition, the content of wherein Berberine hydrochloride is determined, the results are shown in Table 11.The orthogonal examination Face checkings of the Berberine hydrochloride of table 11.

First part of coptis 15g Radixs Astragali 30g 21.9882 of content (mg/g) of sample sample weighting amount Berberine hydrochloride

Second part of coptis 15g Radixs Astragali 30g 22.2236

7. decocting condition is preferred

Semen litchi 24g, kelp 18g are weighed, totally 9 parts, the multiple that adds water, decocting time is selected and decocts three factors of number of times as orthogonal examination Examination investigation factor, each factor respectively takes three levels.Using L₉ ( 3⁴) orthogonal arrage tested, using the content of semen litchi protocatechuic acid as inspection target, factor level design is shown in Table 12.Orthogonal test and 13 are the results are shown in Table, the result in table 13 is carried out after statistical procedures, analysis of variance table is seen（It is shown in Table 14). (add water the horizontal A of the factor level table of table 12. multiple）B (decocting times）C (decoction number of times)

1 6 0.5 1

2 8 1.0 2

The orthogonal test side ^ ^ of 3 10 1.5 3 table 13. and result

Experiment leaching bone protocatechuic acid

A B C D

Sequence number content (mg/)

1 1 1 1 1

2 1 2 2 2

3 1 3 3 3

4 2 1 2 3

5 2 2 3 1

6 2 3 1 2

7 3 1 3 2

8 3 2 1 3

9 3 3 2 1

K1 10.0855 14.619 6.1112 12.4708

k2 13.2996 12.0689 16.009 13.1835 ∑=39.3775 k3 15.9924 12.6896 17.2573 13.7232 CT=172.2875007

S 5.8303421 1.1789848 24.8622492 0.26308030 The protocatechuic acid analysis of variance table of table 14.

Quadratic sum of the originating free degree side and F are than the * B 1.1789848 2 0.5894924 4.481463644 of conspicuousness A 5.8303421 2 2.91517105 22.16183416

The * errors of C 24.8622492 2 12.4311246 94.50441253=D 0.26308030 2 0.13154015

Fl-0.05 (2,2)=19 From above-mentioned variance analysis, A factors and C factors have significant difference, and there was no significant difference for B factors, therefore A factors selection A₃, B factors selection B " C factor selections C₃, i.e. AsB!C^ semen litchis, the optimum extraction condition of kelp are：Extracted three times, every time 0.5 hour with 10 times of amount water.

Experimental study of the pharmaceutical composition in type ii diabetes rat of the present invention show, rat occurs hyperinsulinemia in high fat high-carbonhydrate diet one month and increased with blood glucose and cholesterol, successfully induces insulin resistance.Type ii diabetes rat model is caused after low dose of STZ intraperitoneal injections.Continuous gavage is administered two months, and heavy dose group blood glucose is substantially reduced,（Compared Ρ with model group<0001), hypoglycemic rate reaches 31.23%.Greatly, middle dose group blood fat is substantially reduced (is compared Ρ with model group<0.05~0.001).Illustrate that pharmaceutical composition of the present invention plays the role of hypoglycemic, lipid-loweringing to type ii diabetes rat.

Real face research to speed hair property diabetes rat shows that rat forms speed hair property diabetes (type i diabetes) rat model after injection STZ.Continuous gavage is administered two months, and each dosage group blood glucose of pharmaceutical composition of the present invention is substantially reduced, and is compared with model group（ Ρ<0.05 ).Heavy dose group is compared with model group, and glycosylated hemoglobin and glycosylated hemoglobin percentage are decreased obviously (Ρ<0.05 001), and hyperglycemic factor has declined（Ρ<0.05 ).Insulin level has the trend increased, and food ration has different degrees of decline, but not statistically significant.Illustrate that pharmaceutical composition of the present invention has blood sugar reducing function to speed hair property diabetes rat.

Therefore, the present invention also provides a kind of medicine composite for curing diabetes using the present invention And its method for complication, or the present invention pharmaceutical composition prepare be used for treat the medicine of diabetes and its complication in purposes.Embodiment

Chinese medicine used is purchased from Hebei Anguo Chinese medicine trade market respectively in example below, is identified through relevant expert and through examining, and meets relevant every regulation of China's coastal port one.

Dextrin is purchased from Hebei province's Langfang City starch factory；Lot number： 200308202;Defend the quasi- word (1998) of medicine the 090127th in Ji；Betadex is purchased from fine chemistry trial (demonstration) plant of Nankai University；Lot number： 20000804.Other reagents are all commercially available.

The present invention is further illustrated by the following examples, but the invention is not restricted to these embodiments.Embodiment 1:Pharmaceutical composition of the present invention（Granule) preparation

1. formula

Fruit of glossy privet 9g;Radix Astragali 6g;The coptis 4.5_g;Semen litchi 3g;Kelp 3g;Turmeric 3g;Appropriate dextrin.

2. preparation technology

The fruit of glossy privet is heated to reflux with the ethanol of 6 times of amounts 75%, is extracted three times, 2 hours every time, is merged ethanol extract, decoction is standby；The coptis, the Radix Astragali add the ethanol of 6 times of amounts 50% to be heated to reflux, and extract three times, 2 hours every time, merge ethanol extract, decoction is standby；Turmeric adds the water steam distillation of 10 times of amounts to extract 8 hours after crushing, collects volatile oil, the aqueous solution and the dregs of a decoction are standby；Volatile oil is taken to carry out inclusion with 8 times of amount betadexs and 80 times of amount water, 50 °C are stirred 1 hour, refrigerated overnight, filtration, inclusion complex low temperature drying（40 ' C), fine powder is ground into, it is standby；Semen litchi, kelp add 10 times of amount water, extract three times, 0.5 hour every time, close decoct with the above-mentioned turmeric dregs of a decoction for the third time, collecting decoction, filtration, filtrate merges with the above-mentioned aqueous solution, and amalgamation liquid is concentrated into relative density 1.10-1.15 (50.C is surveyed）, plus ethanol makes to contain Alcohol amount is up to 60%, and ethanol is separately recovered to relative density 1.15-1.20 (50 in refrigerated overnight, filtration, the decoction such as filtrate and the above-mentioned fruit of glossy privet.C is surveyed）, dry, mix and hook in right amount with above-mentioned volatile oil betadex inclusion complex fine powder and dextrin, particle is made, dry, particle is made（10 g ).Embodiment 2:Pharmaceutical composition of the present invention（Tablet）Preparation

1. formula

Fruit of glossy privet 22.5g, Radix Astragali 15g, coptis 4.5g, semen litchi 6g, kelp 7.5g, turmeric 7.5_g, appropriate dextrin.

2. preparation technology

The ethanol heating and refluxing extraction three times of 6 times of amounts 75% of the fruit of glossy privet, 2 hours every time, merges ethanol extract, reclaims ethanol, dry, standby；Turmeric adds 10 times of amount water after crushing, and Shui Zheng Qi Zheng Evaporated are extracted 8 hours, collect volatile oil, the aqueous solution is standby, dregs of a decoction drying for standby；Volatile oil is taken to carry out inclusion, 50 with 8 times of amount betadexs and 80 times of amount water.C is stirred 1 hour, refrigerated overnight, filtration, inclusion complex low temperature drying（40.C), fine powder is ground into, it is standby；Semen litchi, kelp add 10 times of amount water, decoct three times, 0.5 hour every time, collecting decoction, filtration, filtrate merged with the above-mentioned turmeric aqueous solution, and amalgamation liquid is concentrated into relative density 1.10-1.15 (50.C is surveyed）, plus ethanol makes alcohol content up to 60%, refrigerated overnight, filtration, filtrate is standby；The ethanol heating and refluxing extraction three times of 6 times of amounts 50% of the coptis, the Radix Astragali and the turmeric dregs of a decoction, 2 hours every time, merges ethanol extract, merges with upper fan's water decoction-alcohol sedimentation liquid, and reclaiming ethanol, (50 °C are surveyed to relative density 1.15-1.20）, dry, mixed in right amount with above-mentioned fruit of glossy privet leaching bone, betadex inclusion complex fine powder and dextrin, pelletize, dry, tabletting（0.72-0.75g every heavy, totally 9）.Embodiment 3:Pharmaceutical composition of the present invention（Capsule）Preparation

1. formula

The fruit of glossy privet 25.5_g, the g of the Radix Astragali 18, the coptis 7.5 g, semen litchi 7.5g, the g of kelp 9, turmeric 9_g, appropriate dextrin. 2. preparation technology

The ethanol heating and refluxing extraction three times of 6 times of amounts 75% of the fruit of glossy privet, 2 hours every time, merges ethanol extract, reclaims ethanol, dry, standby；Turmeric adds 10 times of amount water after crushing, and steam distillation is extracted 8 hours, collects volatile oil, the aqueous solution is standby, dregs of a decoction drying for standby；Volatile oil is taken to carry out inclusion with 8 times of amount betadexs and 80 times of amount water, 50'C is stirred 1 hour, refrigerated overnight, filtration, inclusion complex low temperature drying（40'C), fine powder is ground into, it is standby；Semen litchi, kelp add 10 times of amount water, decoct three times, 0.5 hour every time, collecting decoction, filtration, filtrate merged with the above-mentioned turmeric aqueous solution, and amalgamation liquid is concentrated into relative density 1.10-1.15 (50.C is surveyed）, plus ethanol makes alcohol content up to 60%, refrigerated overnight, filtration, filtrate is standby；The ethanol heating and refluxing extraction three times of 6 times of amounts 50% of the coptis, the Radix Astragali and the turmeric dregs of a decoction, 2 hours every time, merges ethanol extract, merges with above-mentioned water decoction-alcohol sedimentation liquid, and reclaiming ethanol, (50 °C are surveyed to relative density 1.15-1.20）, dry, mix hook in right amount with above-mentioned fruit of glossy privet leaching bone, betadex inclusion complex fine powder and paste ^lt, pelletize, dry, fill capsule（Every glue Nang weighs 0.43g, totally 15）.Embodiment 4:Pharmaceutical composition of the present invention（Extract clear cream）Preparation

1. formula

The g of the fruit of glossy privet 12, the Radix Astragali 6_g, the coptis 3_g, semen litchi 6_g, kelp 4.5_g, the g of turmeric 4.5, appropriate dextrin.

2. preparation technology

The ethanol heating and refluxing extraction three times of 6 times of amounts 75% of the fruit of glossy privet, 2 hours every time, merges ethanol extract, reclaims ethanol, dry, standby；Turmeric adds 10 times of amount water after crushing, and steam distillation is extracted 8 hours, collects volatile oil, the aqueous solution is standby, dregs of a decoction drying for standby；Volatile oil is taken to carry out inclusion, 50 with 8 times of amount betadexs and 80 times of amount water.C is stirred 1 hour, refrigerated overnight, filtration, inclusion complex low temperature drying（40.C), fine powder is ground into, it is standby；Semen litchi, kelp add 10 times of amount water, decoct three times, 0.5 hour every time, collecting decoction, filtration, filtrate merged with the above-mentioned turmeric aqueous solution, and amalgamation liquid is concentrated into relative density 1.10-1.15 (50 °C of surveys）, plus ethanol makes alcohol content up to 60%, refrigerated overnight, filtration, filtrate is standby；The ethanol heating and refluxing extraction three times of 6 times of amounts 50% of the coptis, the Radix Astragali and the turmeric dregs of a decoction, 2 hours every time, merges ethanol extract, merges with above-mentioned water decoction-alcohol sedimentation liquid, reclaims ethanol to relative density 1.15-1.20 (50'C surveys）, it is well mixed, produces with above-mentioned fruit of glossy privet leaching bone, betadex inclusion complex fine powder.Embodiment 5:Experimental study 1. experiment material of the pharmaceutical composition of the present invention in type ii diabetes rat

1.1. animal

From II grades of rats of Wistar kinds, hero female half and half, body weight 180-200g are provided by Institute of Experimental Animals, Chinese Academy of Medical Sciences, licensing numbering：SCXK capital 2000-0006 is raised in China TCM Academy of Sciences Xiyuan Hospital Experimental Animal Center, secondary animal Rearing facility, quality certification number：SYXK (capital） 2003-0008.Room temperature：22-25 °C, relative humidity： 45-60%.

1.2. feed

Normal diet by Beijing Australia of section pull together feed corporation,Ltd provide, product license number：Raise in capital（Match somebody with somebody）No. 238, perform standard GB14924,3-2001

Main nutrient composition：Crude protein >=18%, crude fibre≤5%, coarse ash≤8%, calcium 0.8-1.8%, upright stone tablet 0.6-1.2%, lysine >=1.35%, salt 0.5%, water ^≤10%, various electrolytes and minerals.

High-sugar-fat-diet is processed by Chinese military medicine academy of sciences Experimental Animal Center.Formula：Lard 10%, sucrose 10%, cholesterol 2.5%, sodium taurocholate 1%, generic word material 76.5%

1.3. medicine

Pharmaceutical composition of the present invention：Experiment extracts clear bone, 3.37 with it_gCrude drug/_gBone, lot number：050401, prepared according to the method shown in embodiment 4.

The Yue biguanides pieces of hydrochloric acid two：0.25g/ pieces, lot number：041226, Beijing Li-Ling Hengtai Pharmaceutical Co., Ltd's production, Chinese medicines quasi-word H11021560. JINQI JIANGTANG PIAN： 0.42_g/ piece, lot number：0503746, Longshunrong Pharmaceutical Factory, Tianjin Zhongxin Pharmaceutical Group Co., Ltd's production, Chinese medicines quasi-word Z10920027.

1.4. reagent

Twist that lemon is sour and the sour sodium of stubborn lemon：Beijing Chemical Plant is produced, lot number： 960904.Streptozotocin（STZ ):Sigma companies produce, lot number：Biological medical science and technology Co., Ltd packing over S0130, Beijing day.Blood sugar test paper：German Roche Holding Ag's production, lot number：22898731, Roche Diagnistics' product（Shanghai）Co., Ltd dispenses.Radioimmunological kit（Insulin, TNF, interleukin-6):Tianjin Jiuding Medical Biological Engineering Co., Ltd produces, lot number： 200510.Biochemical reagents box（T-CHOL, triglycerides）：Zhongsheng Beikong Biological Science ＆ Technology Co., Ltd. produces, lot number： 050331.50% glucose injection：Beijing Double-Crane Pharmaceutical Co., Ltd is produced, lot number： 0502142.

2. experimental method

Experiment sets normal diet group and high-sugar-fat-diet group, and rat is induced insulin resistance after high fat high-carbonhydrate diet is fed one month, then using 25 mg/kg Streptozotocins（STZ) 2 intraperitoneal injections induce hyperglycemia, and fasting blood-glucose is determined after 72 hours, to be used as model success rat more than 16.7mmol/l.Packet：（1) blank control group（Normal diet+0.1M citric acid Slow fliud flushings are injected intraperitoneally）；Following each group is high-sugar-fat-diet plus STZ>0.1M citric acid Slow fliud flushings are injected intraperitoneally,（2) model group；（3) the Yue biguanides groups 0.2g/kg of positive drug two;(4) positive drug JINQI JIANGTANG PIAN group 2g/kg;(5) pharmaceutical composition middle dose group 4g crude drugs/kg of pharmaceutical composition of the invention heavy dose group 8g crude drugs/kg (6) present invention;(7) this bright pharmaceutical composition small dose group 2g crude drugs/kg.In addition to blank control group and model group, each group according to dosage gastric infusion and continue high-sugar-fat-diet feed one month.Body weight and food ration are surveyed weekly, and blood glucose is surveyed every other week.The index such as abdomen active hematometry blood glucose, blood fat, insulin, TNF, interleukin-6 after successive administration two months, anesthesia.Take pancreas, liver to make pathological section, core dirty, liver, kidney are weighed, calculate organ index：Organ weights/body weight xlOO (g/100g).As a result statistical procedures are carried out（T is examined）. 3. experimental result

3.1. influence of the pharmaceutical composition of the present invention to type ii diabetes rat blood sugar

High-sugar-fat-diet group rat determines each group before fasting blood-glucose, medicine after being injected intraperitoneally 72 hours through STZ, and to be compared blood glucose with control group significantly raised（P<0.001), average blood glucose levels illustrate modeling success in 25-26 mmol/l or so.Each group continuous gavage is administered two months, and pharmaceutical composition heavy dose group of the invention is compared with model group, 2,4,6 weeks can reduce rat blood sugar（Ρ<005 ~ 0.01), at 8 weeks act on obvious（Ρ<0.001 ).Hypoglycemic rate reaches that 31.23%. the results are shown in Table 15.Influence of the pharmaceutical composition of the present invention of table 15. to type ii diabetes rat blood sugar

( mmol/1 , χ ±s )

Group, dosage, n, before administration, after medicine, 2 weeks, after medicine, 4 weeks, after medicine, 6 weeks, after medicine, 8 weeks, control group, 12, 5.62 ± 0.39, 5.63 ± 0.42, 5.08 ± 0.32, 5.87 ± 0.49, 4.22 ± 0.61, model group, 11, 26.43 ± 3.01***, 32.19 ± 1.06, * *, 33.00 ± 00, * *, 29.79 ± 3.25, * *, 25.24 ± 3.47, * *, two Yue biguanides groups, 0.2, 12, 25.34 ± 3.40***, 23.33 ± 2.41###, 28.04 ± 4.16###, 25.21 ± 3.21, 17.79 ± 2.65 Gang, golden stilbene, PHI piece groups, 2, 8, 25.54 ± 4.21**, 29.58 ± 2.46##, 31.71 ± 2.61, 26.65 ± 2.70, #, 21.16 ± 3.25#, heavy dose group of the invention, 8, 11, 26.42 ± 3.16***, 28.73 ± 3.58##, 30.81 ± 2.62##, 26.67 ± 3.54#, 17.35 ± 3.13###, middle dose group of the present invention, 4, 10, 26.59 ± 3.79***, 28.95 ± 2.73##, 32.39 ± 1.21, 25.38 ± 2.83##, 26.05 ± 3.85, little Ji Liang Group of the present invention, 2, 11, 26.24 ± 3.81***, 30.83 ± 2.38, 32.83 ± 0.39, 28.94 ± 2.79, 27.05 ± 3.55, compared with control group： * P<0.01 * * * P<0.001 ；

Compared with model group： # Ρ<0·05 ## Ρ<0.01 ### Ρ<0.001

3.2. influence of the pharmaceutical composition of the present invention to type ii diabetes rat fat

Each group continuous gavage is administered two months, and pharmaceutical composition heavy dose group of the invention is compared with model group, can substantially reduce triglyceride levels（Ρ<0.01), middle dose group can obviously reduce triglycerides and total cholesterol level（ Ρ<0.05~0.001 ).It the results are shown in Table 16. 7

The pharmaceutical composition of the present invention of 20 table 16. is to type ii diabetes rat

The influence of blood fat（ ±_S )

The tenth of the twelve Earthly Branches of group dosage T-CHOL glycerine three

n

, (g/kg), (mmol/1), (mmol/1) heavy dose of group # 0.92 ± 0.58### of 8 11 2.05 ± 0.56 1.18 ± 0.49 ## middle dose groups 10 2.01 ± 0.31 of the present invention small dose groups 2 11 2.39 ± 1.08 1.48 ± 0.65 of the present invention of the present invention of 11 2.28 ± 0.27 * * * of ± 0.25 1.05 ± 0.32 model group of control group 12 1.47,1.83 ± 0.42 * * * melbine groups, 0.2 12 2.34 ± 0.99 1.82 ± 0.63 JINQI JIANGTANG PIAN group 28 2.16 ± 0.36 1.52 ± 0.59 are compared with control group： *** P<0.001

Compared with model group： #P<0.05 ## P<0.01 ###P<0.001.

3.3. influence of the pharmaceutical composition of the present invention to indexs such as II patients with type Ⅰ DM rat insulins：

Each group continuous gavage is administered two months, and pharmaceutical composition heavy dose group of the invention is compared with model group, and insulin level has increased（P<0.05).The indexs such as TNF, the interleukin-6 of each dosage group of pharmaceutical composition of the present invention are compared no significant difference with model group.It the results are shown in Table 17.The pharmaceutical composition of the present invention of table 17. is to type ii diabetes rat blood insulin

Etc. the influence of index（ ±S )

The plain TNF interleukin-6 n of Quarry dosage pancreas 2

(g/kg) ( uIU/ml ) ( ng/ml ) ( pg/ml )

12 10.34 ± 1.69 4.10 ± 1.37 149.39 ± 19.23 Utah and 11 9.24 ± 2.39 5.04 ± 1.55 191.07 ± 36.64 * * diformazans) and 4.68 ± 1.19 178.01 ± 36.67 group 28 11.64 ± 3.54 4.64 ± 1.24 179.61 ± 29.80 of 0.2 12 13.29 ± 3.53 ##

8 11 11.41 ± 1.64 # 4.32 ± 1.90 193.52 ± 79.02 pull out Ming Zhong Wrapping and 4 10 10.37 ± 1.25 4.16 ± 0.75 234.76 ± 64.22

2 11 1057 ± 1.76 4.13 ± 1.08 234.84 ± 28.93## are compared with control group： ** P<0.01 ；Compared with model group： #P<0.05 ##P<0.01. 3.4. influence of the pharmaceutical composition of the present invention to type ii diabetes rat body weight

Each group body weight is compared with control group and has different degrees of decline after STZ injections, from the

Start to be decreased obviously within 2 weeks（P<0.05~0.001).Continuous gavage is administered after two months, and rat body weight can not still recover to modeling.It the results are shown in Table 18 and 19.The pharmaceutical composition of the present invention of table 18. is to type ii diabetes rat body weight

Influence（Gram, ^ ± 5)

4 weeks unicorns and 12 306.33 ± 61.00 315.17 ± 63.92 319.17 ± 68.46 315.58 ± 62.61 327.75 ± 69.55 Surface and the Yue of 11 282.18 ± 46.51 289.82 269.64 ± 45.55 253.91 ± 44.61* of ± 46.66 258.55 ± 41.44* bis- and 0.2 12 284.42 ± 56.72 290.33 ± 51.60 263.75 ± 46.22* 275.92,28 281.25 ± 42.93 295.67 266.00 ± 33.23* of ± 44.08 262.33 ± 32.69*, 261.08 ± 31.70** of ± 47.27 271.33 ± 47.77* gold ^ pieces group are extremely bright after 3 weeks medicines after 2 weeks medicines after 1 week medicine after punishment amount n administration prodrugs;<^'J and 8 11 278.83 ± 49.15 291.00 ± 46.15 257.18 ± 40.42* 252.7 ± 33.26**, 256.73 ± 37.60** pole Ming Zhong Wrapping and 4 10 282.42 ± 61.16 289.08 264.42 ± 44.81* of ± 56.83 251.3 ± 42.20**, 258.33 ± 42.60** it is extremely bright ' the pharmaceutical composition of the present invention of ± 48.83 276.17 ± 33.55 237 ± 29.98*** 247.4 ± 31.12**, 242.17 ± 30.36*** tables of J^ a 2 11 279.42 19. is to type ii diabetes rat body weight

Influence（Gram, ^is)

After dosage n medicines after 5 weeks medicines after 6 weeks-medicine 8 weeks after 7 weeks medicines

^Sfand 12 329. "±70.84 333.58±72.38 339.67±74.63 340.83±74.60 maiand 11 269.18±47.28* 243.1±65.37** 244.4±54.25** 234.64±56.95*** er jia and 0.2 12 273.08±41.52* 261.0±36.23** 265.7±42.31** 230.17±38.87*** pian zhu 2 8 262.91±37.20* 231.73±32.92*** 242.27±31.47*** 242.25±22.98** 8 11 261.7±34.33** 249.5±39.01** 259.6±36.35** 230.09±26.93*** 4 10 265.58±51.72* 236.75±48.56*** 244.9±51.73** 228.70±52.70*** 2 11 255.33±36.48** 244.82±39.38** 241.73±33.59*** 229.45±27.99***

Compared with control group： * P<0.05 ** P<0.01 *** P<0.001 3.5. pharmaceutical composition of the present invention to each group rat food ration after the influence STZ of type ii diabetes rat food ration injection with control group is obvious increases, from 0 week（Not yet start administration after injection STZ）Start just have notable difference（ P<0.05 ~ 0.01), the symptoms that drink more is eaten diabetes obvious more.After gastric infusion 3 weeks, each dosage group of pharmaceutical composition of the invention is compared with model group, and food ration has different degrees of decline, significant difference (P at 4 weeks<0.05).Illustrate the reduction with blood sugar level, the symptom of diabetes has mitigated.It the results are shown in Table 20 and 21.20., table！Bright pharmaceutical composition is to type ii diabetes rat food ration

Influence (g material/100g body weight, a

4 weeks ± 4.78 12.44 ± 1.29' of 12 5.79 ± 0.78 6.64 ± 1.01 5.00 ± 1.23 6.27 ± 0.28 5.34 ± 1.24 model groups of Dui Zhao Group 11 13.34 after 3 weeks medicines after 2 weeks medicines after 1 week medicine after 0 week medicine after group n medicines^k18.86 ± 0.88*', *, 19.56 ± 2.08*, 21.93 ± 0.62**, melbine group, 12, 14.26 ± 2.82, 11.46 ± 3.90, 15.17 ± 2.13, 14.73 ± 0.20, 1367 ± 063##, JINQI JIANGTANG PIAN group, 8, 11.61 ± 1.65*, 12.78 ± 0.72, 13.79 ± 0.88#, 14.49 ± 0.58, 15.9 ± 022##, heavy dose group of the invention, 11, 14.15 ± 0.07**, 14.39 ± 0.86, 18.92 ± 2.75, 17.10 ± 1.49, 18.48, 08#, middle dose group of the present invention, 10, 13.28 ± 0.67**, 12.75 ± 2.11, 17.81 ± 1.29, 17.78 ± 0.36, 17.49 ± 2.08, small dose group of the present invention, 11, 11.41 ± 1.64*, 12.68 ± 0.70, 16.92 ± 1.14, 16.03 ± 1.28, 15.13 ± 1.22#, table, 21., pharmaceutical composition pair of the present invention, the influence of type ii diabetes rat food ration, ± s, ), group, n, after medicine, 5 weeks, after medicine, 6 weeks, after medicine, 7 weeks, after medicine, 8 weeks, control group, 12, 3.59 ± 0., 35, 5.31 ± 1.34, 4'40 ± 0.07, 4.78 ± 0.11, model group, 11, 18.30 ± 0.94**, 19.68 ± 0.61**, 21.56 ± 3.21*, 20.48 ± 4.22*, melbine group, 12, 1338 ± 1, .79, 15.31 ± 1.59, 16.96 scholar 2.60, 15.59 ± 2.65, golden stilbene, PHI piece groups, 8, 14.12 ± 0., 51#, 18.26 ± 1.19, 16.63 ± 1.03, 20.36 ± 3.87, heavy dose group of the invention, 11, 1642 ± 3, .41, 21.29 ± 1.45, 18.17 ± 0.44, 18.24 ± 1.78, middle dose group of the present invention, 10, 16.46 ± 0, .80, 17.99 ± 7.81, 18.25 ± 0.67, 18.00 ± 3.08, small dose group of the present invention, 11, 16.83 ± 1, .76, 17.54 ± 1.65, 16.78 ± 1.30, 16.71 ± 1.89

Compared with control group： *Ρ<0.05 ** Ρ<0.01;Compared with model group： # Ρ<0.05 ## Ρ<0.01 3.6. influence of the pharmaceutical composition of the present invention to diabetes rat organ index

Each group organ index rises that this is relevant with Body weight loss after STZ injections, the results are shown in Table 22.Influence of the table 22. to type ii diabetes Rats Organs and Tissues index

(unit：G/100g body weight, ± s)

12 0.344 ± 0.068 2.395 ± 0.122 0.292 ± 0.038 0.488 ± 0.049*** of model group 11 0.416 ± 0.043**, 4.549 ± 0.393*** of group dosage n cardiac index liver index renal indexes control group bis-, 0.483 ± 0.043*** of Yue biguanides group 0.2 12 0.438 ± 0.041***, 4.900 ± 0.394***, 0.471 ± 0.053*** JINQI JIANGTANG PIAN group 28 0.402 ± 0.029*, 4.856 ± 0.253***, 0.499 ± 0.058***, 8 11 0.443 ± 0.067** of instrumcnts of torture amount group of the present invention, 4.954 ± 0.603* ", 0.483 ± 0.050***, 4 12 0.396 ± 0.039* of middle dose group of the present invention, 4.731 ± 0.508***, 0.466 ± 0.026*** small punishment amount group 2 11 0.437 ± 0.051**, 4.810 ± 0.304*** of the present invention are compared with control group： * P<0.05 ** P<0.01 *** ρ<ο.οοι

4. conclusion

Increase test result indicates that hyperinsulinemia occurred in high fat high-carbonhydrate diet one month for rat with blood glucose and cholesterol, successfully induce insulin resistance.Type ii diabetes rat model is caused after STZ intraperitoneal injections.Continuous gavage is administered two months, and heavy dose group blood glucose is substantially reduced, and hypoglycemic rate reaches 31.23%.Greatly, middle dose group blood fat is substantially reduced.Illustrate that pharmaceutical composition of the present invention plays the role of hypoglycemic, lipid-loweringing to type ii diabetes rat.Embodiment 6:Pharmaceutical composition of the present invention is in anaphylactic type diabetes Γ patients with type Ⅰ DM）

Experimental study in rat

1. experiment material

1.1. animal

From II grades of male rats of Wistar kinds, body weight 180-200g, by China Medical Science Institute of lab animals of institute is provided, licensing numbering：SCXK capital 2000-0006.Raised in China TCM Academy of Sciences Xiyuan Hospital Experimental Animal Center, secondary animal Rearing facility, quality certification number：Dynamic word (capital) SYXK the 2003-0008th of doctor.Room temperature：22-25'C, relative humidity： 45-60%.

1.2. Feeding expects

By Beijing Australia of section pull together feed corporation,Ltd provide, product license number：Raise in capital（Match somebody with somebody）No. 238, perform standard GB14924,3-2001. main nutrient composition：Crude protein >=18%, crude fibre≤5%, cinder ^≤8%, calcium 0.8-1.8%, phosphorus 0.6-1.2%, lysine >=1.35%, salt 0.5%, moisture≤10%, various electrolytes and minerals.

1.3. medicine

Pharmaceutical composition of the present invention：Experiment extracts clear cream, 3.37 with it_gCrude drug/_g, lot number：050401, prepared according to the method shown in embodiment 4.

Metformin hydrochloride tablet：0.25g/ pieces, lot number：041226, Beijing Li-Ling Hengtai Pharmaceutical Co., Ltd's production, Chinese medicines quasi-word H11021560.

JINQI JIANGTANG PIAN： 0.42_g/ piece, lot number：0503746, Longshunrong Pharmaceutical Factory, Tianjin Zhongxin Pharmaceutical Group Co., Ltd's production, Chinese medicines quasi-word Z10920027.

1.4. reagent

Citric acid and sodium citrate：Beijing Chemical Plant is produced, lot number： 960904.Streptozotocin（STZ ):Sigma companies produce, lot number：Biological medical science and technology Co., Ltd packing over S0130, Beijing day.Blood sugar test paper：German Roche Holding Ag's production, Roche Diagnistics' product (Shanghai）Co., Ltd dispenses, lot number： 22898731.Insulin radioimmunological kit：Fu Rui bio-engineering corporations of Beijing, lot number： 200601.Hyperglycemic factor radioimmunological kit：Beijing Atom HighTech Co., Ltd., lot number： 200601.Glycosylated hemoglobin：German Roche Holding Ag's production, lot number： 200512.

2. experimental method

Test and select II grades of male rats of Wistar kinds, body weight 180-200g, Ge Group uses Streptozotocin in addition to blank control group（STZ) tail vein injection（90mg/kg, 0.1M lemon Lemon acid Slow fliud flushings are prepared）Modeling, fasting blood-glucose is determined after 72 hours, to be used as model success rat more than 16.7mmol/l.Packet：(1) blank control group（2) model group；（3) the Yue biguanides groups 0.2g/kg of positive drug two;(4) positive drug JINQI JIANGTANG PIAN group 2g/kg;(5) pharmaceutical composition of the invention heavy dose group 8_gThe pharmaceutical composition middle dose group 4 of crude drug/kg (6) present invention_gCrude drug/kg;(7) pharmaceutical composition small dose group 2g crude drugs/kg of the invention.The each group according to dosage gastric infusion in addition to blank control group and model group.Body weight is surveyed weekly, and blood glucose is surveyed every other week.Abdominal aorta takes whole blood (25ulEDTA+lml whole blood anti-freezings after anesthesia）Determine glycosylated hemoglobin, separation serum and determine insulin, separated plasma（25ulEDTA+lml whole blood anti-freezings）Determine the indexs such as hyperglycemic factor.Pancreas is taken to make pathological section（HE is dyed and aldehyde-fuchsin spy's dye）.As a result statistical procedures are carried out（T examines face）.

3. result

3.1. influence of the pharmaceutical composition of the present invention to anaphylactic type blood glucose in diabetic rats

Rat is through Streptozotocin（STZ) tail vein injection determines each group before fasting blood-glucose, medicine to be compared blood glucose with control group significantly raised after 72 hours（P<0.001), average blood glucose levels exist

23-24 mmol/l or so, illustrate modeling success.Each group continuous gavage is administered two months, and pharmaceutical composition of the invention is big, middle dose group is compared with model group, there is blood sugar reducing function (P at 6 ~ 8 weeks<0.05), there is blood sugar reducing function during small dose group 8 weeks（P<0.05 ).It the results are shown in Table 23.The pharmaceutical composition of the present invention of table 23. is to anaphylactic type blood glucose in diabetic rats

Influence

Blood glucose (mmol/l)

Group n：^: ~

Before administration, after medicine, 2 weeks, after medicine, 4 weeks, after medicine, 6 weeks, after medicine, 8 weeks, control group, 13, 6.53 ± 0.43, 6.32 ± 0.32, 6.46 ± 0.53, 6.39 ± 0.43, 5.39 ± 0.32, model group, 13, 23.27 ± 3.48***, 29.38 ± 3.48***, 29.85 ± 2.17***, 28.75 ± 1.40***, 28.99 ± 2.30***, Er first Shuan Gua Group, 12, 23.61 ± 2.38***, 25.91 ± 2.61, ##, 25.36 ± 4.83, mt, 18.43 ± 9.36, ###, 22.51 ± 3.50, wake up, JINQI JIANGTANG PIAN group, 11, 24.08 ± 2.69***, 27.23 ± 2.50, 26.82 ± 5.45, 27.42 ± 3.88, 26.66 ± 3.53, instrumcnts of torture amount group of the present invention, 11, 23.13 ± 2.64***, 28.30 ± 5.24, 27.25 ± 5.17, 24.98 ± 5.37, #, 25.02 ± 5.72, #, middle dose group of the present invention, 12, 23.50 ± 2.92***, 29.50 ± 3.25, 29.11 ± 2.62, 26.88 ± 2.02, #, 25.58 ± 4.50, #, small dose group of the present invention, 10, 23.64 ± 3.44***, 29.20 ± 3.21, 28.58 ± 1.73, 28.34 ± 2.09, 25.50 ± 5.36, #, compared with control group: "* P<0.001;Compared with model group: # P<0.05 ## P<0.01 ### P<0.001. 3.2. influence of the pharmaceutical composition of the present invention to anaphylactic type diabetes rat glycosylated hemoglobin

Each group continuous gavage is administered two months, and pharmaceutical composition heavy dose group of the invention is compared with model group, glycosylated hemoglobin（HBAlc) declined（P<0.05), the ^^ ratios of glycosylated hemoglobin hundred（Halc%) it is decreased obviously（P<0.01), hemoglobin（HB) no significant difference is compared with model group.It the results are shown in Table 24.Influence of the pharmaceutical composition of the present invention of table 24. to indexs such as anaphylactic type diabetes rat glycosylated hemoglobins（7 ± 5) heavy dose of group 8 11 704 ± 080## of g/kg, 0.92 ± 0.20# 16.81 ± 1.36,4 g/kg of middle dose group 12 7.43 ± 0.73 1.04 ± 0.21 17.60 ± 1.80 of the present invention small dose group 2Rkg 10 7.59 ± 0.79 1.06 ± 0.25 17.36 ± 3.24 of the present invention of the present invention of 13 3.60 ± 0.08 0.27 ± 0.04 17.94 ± 3.14 13 7.83 ± 0.47*** of model group, 1.10 ± 0.19***, 17.35 ± 2.51 melbine groups, 0.2 12 7.38 ± 0.47# of g/kg, 0.92 ± 0.16#, 15.69 ± 2.00 2/kg of JINQI JIANGTANG PIAN group of group dosage n Hale % HBAlc HB control groups 11 7.39 ± 0.73 1.02 ± 0.17 17.36 ± 1.35 compared with control group： * ' P<0.05 *** P<0.001;Compared with model group： #P<0.05 ##P<0.01.

3.3. influence of the pharmaceutical composition of the present invention to anaphylactic type diabetes rat insulin and hyperglycemic factor

Each dosage group continuous gavage of pharmaceutical composition of the present invention is administered two months, is compared with model group, insulin level, which has, increases trend, but not statistically significant.Heavy dose group is compared with model group, and hyperglycemic factor has declined（P<0.05).It the results are shown in Table 25. Influence of the pharmaceutical composition of the present invention of table 25. to anaphylactic type diabetes rat blood insulin and hyperglycemic factor（：）

Group punishment Liang Yi Island element hyperglycemic factors

n

(g/kg) ( ulU/ml ) ( g/ml )

Heavy dose of group 8 11 4.88 ± 1.23 350.35 ± 73.99 # middle dose groups 4 12 5.34 ± 1.49 380.11 ± 130.68 of the present invention small dose group 2 10 4.85 ± 0.85 406.54 ± 140.05 of the present invention of the present invention of 13 4,72 ± 1.79 * * * of ± 7.18 219.72 ± 42.88 model group of control group 13 14.92,445.63 ± 134.52 * * * melbine groups, 0.2 12 5.51 ± 2.21 337.35 ± 70.83 # JINQI JIANGTANG PIANs group 2 11 4.38 ± 1.81 349.39 ± 96.65

Compare with compareing i： * ** P<0.001;Compared with model group： #P<0.05.

3.4. influence of the pharmaceutical composition of the present invention to anaphylactic type diabetes rat body weight

Start to be decreased obviously within 2 weeks（P<0.05~0.001).Continuous gavage is administered after two months, and rat body weight can not still recover to modeling.It the results are shown in Table 26.The pharmaceutical composition of the present invention of table 26. is to anaphylactic type diabetes rat body weight

Influence（Gram, ^ ± s)

After group administration prodrug 4 weeks after 2 weeks medicines ' 8 weeks control groups 227.00 ± 8.75 after 6 weeks medicines after medicine

± 35 202.23 ± 11.31 227. .31 of .39 model groups of 366 387., 92 ± 26. .74 of .39 ± 23 .19 of ± 16 .01 of 312. .46,421 .31 ± 19 .64 254 .62 ± 27. .96 233 .31 ± 32 .11 240 .15 ± 35 .56

Bis- Yue biguanides groups of * * * * * * * * * * * * * * 198.62 ± 14.84 217. .77 ± 23 .46 222, the .08 of the .58 of .00 ± 23 .03 206 ± 33

* * * 204. .17±41, .23

# JINQI JIANGTANG PIANs group 199.46 ± 9.58 216 .83 ± 23 .47 206, the .82 of .00 ± 21 .47 201 ± 24 .09

* * * 216. .85±12, .69

Heavy dose of group 195.21 ± 17.90 213 .86 ± 31. .37 of the ## ## present invention

196.69 ± 10.65 205. .69 of punishment amount group ± 21. .28 224 .69 ± 22 .01 in the .08 of 212., 57 ± 25. .40 of * *, 220. ± 39. .05 of .23,213 .82 ± 37 present invention

The .36 of ± 34 .05 of the 71# of ± 32. .76 of 207. .25 208. 25 ± 37. ± 15.85 200. .00 of small dose group 19769 of the present invention 201., 20 ± 41.

194.50 ± 41.90## of * 21050 ± 37.02## of * are compared with control group： *** Ρ<0.001;Compared with model group： #Ρ<0.05 ##Ρ<0.01ο 3.5. influence of the pharmaceutical composition of the present invention to anaphylactic type diabetes rat food ration

After STZ injections each group rat food ration with control group is obvious increases, from 0 week（Not yet start administration after injection STZ）Start just have notable difference（P<0.05-0.001) symptom that many drinks, are eaten diabetes obvious more.After gastric infusion 2 weeks, pharmaceutical composition of the invention is big, middle dose group is compared with model group, and food ration has different degrees of decline, but not statistically significant.With the reduction of blood sugar level, the symptom of diabetes has mitigated.The pharmaceutical composition of the present invention of table 27. be the results are shown in Table to anaphylactic type diabetes rat

The influence of food ration（Gram,

8 weeks bis- 23.90 ± 6.13* of Yue biguanides group 36.19 ± 1.74***, 26.21 ± 2.46***, 24.76 ± 3.21**, 23.63 ± 2.64**, 23.89 ± 1.22*** JINQI JIANGTANG PIAN 33.81 ± 3.67** of group of ± 0.36 9.44 ± 0.41 8.22 ± 0.02 7.55 ± 0.57 6.63 ± 0.43 28.37 ± 4.14** of model group 37.66 ± 3.22***, 35.62 ± 7.08**, 28.97 ± 6.02**, 26.40 ± 8.22* of control group 11.57 21.82,29.78 ± 4.19** of ± 7.44 20.85 ± 1.76*** instrumcnts of torture amount groups of the present invention, 34.07 ± 5.10** 25.03 ± 1 after 6 weeks medicines after 4 weeks medicines after 2 weeks medicines after 0 week medicine after group medicine,32.61 ± 4.58** of 27*** 24.22 ± 2.77**, 19.11 ± 3.73*, 25.14 ± 1.74***, 37.82 ± 4.27*** of middle dose group of the present invention, 31.49 ± 4.83**, 29.87 ± 4.79**, 20.31 ± 6.81 29.25 ± 1.26***, 38.68 ± 5.47** of small dose group of the present invention, 36.13 ± 7.77**, 32.95 ± 1.78***, 31.66 ± 2.07*** are compared with control group： * Ρ<0.05 ** ρ<0.01 *** Ρ<0.001.

4. conclusion

Rat forms anaphylactic type diabetes (type i diabetes) rat model after injection STZ.Continuous gavage is administered two months, and each dosage group blood glucose of pharmaceutical composition of the present invention is substantially reduced.Heavy dose group is compared with model group, and glycosylated hemoglobin and glycosylated hemoglobin percentage are decreased obviously, and hyperglycemic factor has declined.Insulin level has the trend increased, and food ration has different degrees of decline, but not statistically significant.Illustrate that pharmaceutical composition of the present invention has blood sugar reducing function to anaphylactic type diabetes rat.

Claims

Claim

1. the pharmaceutical composition for adjusting blood glucose, blood fat, it includes the Chinese medicine or its extract of following parts by weight：Fruit of glossy privet 5-17, Radix Astragali 3-12, coptis 1-5 and semen litchi 1-5, and pharmaceutically acceptable auxiliary material.

2. the pharmaceutical composition for adjusting blood glucose, blood fat, it is made up of the Chinese medicine or its extract of following parts by weight：Fruit of glossy privet 5-17, Radix Astragali 3-12, coptis 1-5, semen litchi 1-5, kelp 1-6 and turmeric 1-6.

3. pharmaceutical composition according to claim 2, it is made up of the Chinese medicine or its extract of following parts by weight：Fruit of glossy privet 8-15, Radix Astragali 4-10, coptis 2-3, semen litchi 3-4, kelp 3-5 and turmeric 3-5.

4. pharmaceutical composition according to claim 2, it is made up of the Chinese medicine or its extract of following parts by weight：The fruit of glossy privet 8, the Radix Astragali 4, the coptis 2, semen litchi 4, kelp 3 and turmeric 3.

5. according to the pharmaceutical composition of any one of Claims 1-4, wherein the extract is alcohol extracting thing, water extract or volatile oil.

6. according to the pharmaceutical composition of any one of Claims 1-4, it is characterized in that using one annex IB of China's coastal port photograph thin-layered chromatography and when being detected respectively using oleanolic acid, Berberine hydrochloride, Radix Astragali Yue glycosides and protocatechuic acid as reference substance, the pharmaceutical composition manifests the spot of same color on the corresponding position of the reference substance.

7. according to the pharmaceutical composition of any one of Claims 1-4, it is characterized in that using one annex VI D of China's coastal port photograph thin-layered chromatography and when being detected using oleanolic acid and ursolic acid as reference substance, the content of oleanolic acid and ursolic acid in pharmaceutical composition is no less than 4.0 mg and 1.0 mg.

8. a kind of method for the pharmaceutical composition for preparing any one of Claims 1-4, it comprises the following steps：

The fruit of glossy privet is heated to reflux with ethanol, is extracted multiple, is merged alcohol extract, reclaims alcohol, Extract drying for standby；

Turmeric is extracted with steam distillation, collects volatile oil, the aqueous solution and the dregs of a decoction are standby；Gained volatile oil cyclodextrin and water inclusion, are stirred, and are refrigerated, filtration, and gained inclusion complex low temperature drying is crushed, standby；

With decocting repeatedly, collecting decoction, filtration, filtrate merges with the above-mentioned turmeric aqueous solution for semen litchi, kelp, concentrates, plus alcohol, refrigerates, and filtration obtains water decoction-alcohol sedimentation liquid standby；And

The coptis, the Radix Astragali are heated to reflux with the above-mentioned turmeric dregs of a decoction with alcohol, extract multiple, merge alcohol extract and merge with above-mentioned water decoction-alcohol sedimentation liquid, reclaim alcohol, dry and mixed with above-mentioned fruit of glossy privet alcohol extracting thing, turmeric cyclodextrin inclusion complex fine powder, when needing again with pharmaceutically acceptable auxiliary materials and mixing, required formulation is made.

9. the pharmaceutical composition for adjusting blood glucose, blood fat, it is prepared by the method for claim 8.

10. the pharmaceutical composition of any one of Claims 1-4 is preparing the purposes in being used to treat the medicine of diabetes and its complication.