CN107184966A - A kind of pharmaceutical composition for preventing and treating diabetes and its complication - Google Patents

Abstract

The invention discloses a kind of pharmaceutical composition for preventing and treating diabetes and its complication, its drug regimen composition composition：Sea cucumber polypeptide, brown alga oligose, kudzu root extract, water Herba Spirodelae extract, Radix Trichosanthis extract, pink extract, ginkgo biloba p.e, hirudin and Nattokinase.The present invention can treat the diabetes of insulin-resistant, active ingredient compounding than single component to prevention and treatment diabetes effect more preferably, but also some chronic complicating diseases extremely adjoint with blood glucose rise can be prevented and treated；Simple production process of the present invention, cost are low, high efficiency, economic benefit, social benefit are notable.

Description

A kind of pharmaceutical composition for preventing and treating diabetes and its complication

Technical field

The invention belongs to pharmaceutical technology field, more specifically to a kind of medicine for preventing and treating diabetes and its complication Composition.

Background technology

Diabetes turn into the three big chronic diseases for threatening human health, according to IDF（IDF）Statistics, 2010 300,000,000 are reached, the year two thousand thirty number is up to 3.36 hundred million, wherein more than 95% belongs to type II diabetes, its pathological manifestations is Insulin resistance and persistence hyperglycaemia is formed by islet cell function caused insulin secretion relative deficiency of lacking of proper care, generally More by insulin resistance, then occurs the phenomenon of hypoinsulinism again, that is, it is II type glycosuria for the treatment of to treat insulin resistance The key point of disease.Insulin resistance is that the insulin of normal dose produces a kind of state less than its natural biological effect, i.e., Organize to decline the sensitiveness of insulin, compensatory causes the increase of islet β cell insulin, so as to cause hyperinsulinemia Disease, insulin resistance is the basic reason for producing the chronic complicating diseases such as dyslipidemia, angiocardiopathy, that is, reduces insulin and support Anti-, improve the sensitiveness of insulin turns into the important means of successful treatment type II diabetes.

It is clinically extensive using Western medicine hypoglycemic medicines such as insulin, biguanides, sulfonylurea and non-sulfonylureas at present, Although hypoglycemic effect substantially, has certain adverse reaction：Arrhythmia cordis, gastrointestinal discomfort, hypoglycemia, liver kidney work( Energy infringement, metabolic disorder etc..Therefore find hypoglycemic effect substantially, adverse reaction is few, can effectively control symptom, assist body Metabolism restores balance and reduced the medicine of complication, there is important clinical meaning.

The content of the invention

In view of the deficienciess of the prior art, preventing and treating diabetes and its complication object of the present invention is to provide one kind Pharmaceutical composition, the diabetes of insulin-resistant can be treated, active ingredient compounding is than single component to prevention and treatment Diabetes effect more preferably, but also can prevent and treat some chronic complicating diseases extremely adjoint with blood glucose rise；The present invention Simple production process, cost are low, high efficiency, economic benefit, social benefit are notable.

To achieve the above object, the invention provides following technical scheme：

A kind of pharmaceutical composition for preventing and treating diabetes and its complication, it is characterised in that：Its drug regimen composition is constituted：Sea cucumber is more Peptide, brown alga oligose, kudzu root extract, water Herba Spirodelae extract, Radix Trichosanthis extract, pink extract, ginkgo biloba p.e, leech Element and Nattokinase.

As a kind of technical scheme of optimization, the weight ratio of its drug regimen composition is：0.5-1.5 parts of sea cucumber polypeptide, it is brown 2-3 parts of algae oligosaccharides, 3-4 parts of kudzu root extract, 4-6 parts of water Herba Spirodelae extract, 4-6 parts of Radix Trichosanthis extract, pink extract 4-6 Part, 3-4 parts of ginkgo biloba p.e, 0.1-0.5 parts of hirudin, 1-2 parts of Nattokinase.

As a kind of technical scheme of optimization, the brown alga oligose be by fresh sea-tangle by enzymolysis, alcohol precipitation, filtering, concentration, The small molecule monose for refining and being made.

As a kind of technical scheme of optimization, the pink extract is to be extracted by peach kernel, safflower and obtained through alcohol reflux Pink extract.

As a kind of technical scheme of optimization, the weight ratio of its drug regimen composition is：1 part of sea cucumber polypeptide, brown alga oligose 2 Part, 3 parts of kudzu root extract, 4 parts of water Herba Spirodelae extract, 4 parts of Radix Trichosanthis extract, 4 parts of pink extract, ginkgo biloba p.e 3 Part, 0.2 part of hirudin, 2 parts of Nattokinase.

It is used as a kind of technical scheme of optimization, it is characterised in that：Its preparation method is as follows：

1）, sea cucumber with 1-2% neutral proteinases degrade 8-10h, 50-70% ethanol extract 2-3 time, it is each 2-3 hour, filtering, conjunction And filtrate, ethanol is reclaimed, ethanol extract is obtained, concentrated, dries, obtains sea cucumber polypeptide extract；

2）, the root of kudzu vine with 1.5-2% cellulase degradations 8-10h, 50-70% ethanol extract 2-3 time, it is each 2-3 hour, filtering, conjunction And filtrate, concentrate, dry, obtain kudzu root extract；

3）, fresh sea-tangle with 1.5-2% enzymes degrade 10-12h, 60-70% ethanol extract 2-3 time, it is each 2-3 hour, filtering, merging filter Liquid, reclaims ethanol, obtains ethanol extract, concentrates, and dries, obtains brown alga oligose extract.

4）, water duckweed with 30-60% ethanol extract 2-3 time, it is each 2-3 hour, filtering, recovery ethanol extract, concentrate, Dry, obtain water Herba Spirodelae extract.

5）, root of Chinese trichosanthes with 30-90% alcohol refluxs extract 2-3 time, it is each 2-3 hour, filtering, merging filtrate, concentrate, do It is dry, obtain Radix Trichosanthis extract.

6）, peach kernel and safflower extracted 2-3 time with 60-90% alcohol refluxs, each 1-2 hours, merging filtrate, recovery ethanol, Concentration, dries, obtains pink extract.

7）, ginkgo leaf extracted 2-3 time with 30-90% alcohol refluxs, each 2-3 hour, filtering rotates ethanol, and concentration is dry It is dry to obtain ginkgo biloba p.e.

8）, leech in the physiological saline of 10 multiple doses, extract in two times at 70 DEG C, each 30min, obtain preferable leech Element.

9）, in the inoculation that separates from natto to fluid nutrient medium, it is incubated at 37 ± 1 DEG C, from The heart takes supernatant, obtains Nattokinase crude extract；

10）, choose 1 portion of sea cucumber polypeptide, 2 portions of brown alga oligoses, 3 portions of kudzu root extracts, 4 portions of water Herba Spirodelae extracts, 4 portions of roots of Chinese trichosanthes carry Thing, 4 parts of pink extracts, 3 parts of apricot leaf extracts, 0.2 part of hirudin, 2 parts of Nattokinases are taken, then choose 1.5 parts of citric acids, 3 Part radix glycyrrhizae and 12 parts of white granulated sugar mixed dissolutions, deodorization seasoning allotment oral formulations.

By adopting the above-described technical solution, compared with prior art, the beneficial effects of the invention are as follows：

1）, sea cucumber polypeptide be to be by fresh sea cucumber by neutral protease enzymolysis, alcohol precipitation, separation concentration, the molecular weight that is refining to obtain Less than 2000 small peptide, with very strong oxidation resistance, with good dissolubility, stability, low viscosity, suction easy to digest The special physicochemical property such as receipts, no antigen, edible safety, i.e., it is such as antitumor, immune to adjust with a variety of physiological active functionses Section, reduction cholesterol, anti-oxidant, promotion growth, reducing blood lipid, in addition, there is good, numerous studies card to auxiliary hyperglycemic It is bright：Its mechanism of action is probably to suppress small intestine alpha-glucosidase activity, reduces the intake of glucose；Skeletal muscle hexose is improved to swash Enzymatic activity, accelerates glucose phosphorylation process and then improves internal glucose metabolism and utilization；Beta Cell of islet is repaired in protection, Promote insulin secretion, reliable foundation is provided for hypoglycemic drug.

2）, the stability of brown alga oligose in itself it is very strong, with multinomial biological function, have in terms of medicine widely should With can stimulate the breaking up of various immunocompetent cells, ripe, breeding, be that the immune system of body is restored and strengthened, pass through Immunoregulation effect plays various physiological functions.The hypoglycemic study mechanism of brown alga oligose is not yet ripe, and researcher is few with brown alga Sugar is fed raises the diabetic mice set up with high glucose and high fat feed, it is found that the insulin resistance of diabetic mice has changed It is kind, compared with model control group, found with experimental mice：Mouse Kidney week, epididymis, the white adipose weight subcutaneously located and Fat body ratio is significantly reduced；Fasting blood-glucose, the reduction of Diagnostic Value of Fasting Serum insulin, the rise of Serum adiponectin content, phylaxin, leptin contain Amount reduction, its mechanism tentatively judge be improve Adipocyte Factor parasecretion it is relevant, serve hypoglycemic effect.

3）, the dry root that the root of kudzu vine is the wild root of legume, be a kind of famous Chinese medicine.According to now a large amount of studies of pharmacy, Pueraria lobota Root contains many active components, and such as Flavonoid substances (Gly, Acetylpuerarin, arachidic acid etc.) are recorded according to pharmacopeia, these Composition have it is antipyretic promote the production of body fluid, invigorating vital function and promoting eruption, the effects such as relieving muscles diaphoresis.Kudzu root extract is wild dry root by enzyme degraded, alcohol precipitation The active matter for obtained small molecule of forming sediment, its active component is divided into isoflavones (Puerarin, daidzin, daidzein, genistein). Puerarin auxiliary hyperglycemic has obvious effect, and flavone compound has effect for reducing blood fat, can reduce serum cholesterol, reduction oil Three esters, have good effect for treating the cardiovascular and cerebrovascular diseases such as hyperglycaemia, high fat of blood.Pueraria Flavonid and Puerarin can improve the heart The oxygen metabolism of flesh, beneficial effect is produced to myocardial metabolism, therefore can use preventing and treating myocardial ischemia, myocardial infarction, arrhythmia cordis, high blood Pressure, artery sclerosis chronic diseases disease.

5）, water duckweed be Lemnaceae water surface floating plant, be a herb, autonomic drug, happiness wet is waited and wet environment, is avoided Severe cold.The water soluble vitamin such as vitamin B1 containing volume, B2, C, glucoside containing apiolin, two carbochain flavones of light Vitexin type The Huangs such as glucoside, Cyanidin -3- glycosides, cyanidenon -7- β-glycoside, 8- hydroxyl cyanidenon -8- β-glycoside The material such as ketone, linoleic acid, leukotrienes and iodine, bromine, various composition rich content, the effects such as having expelling wind to resolve the exterior, dry antipruritic.According to Research finds that water duckweed is a lot of as the research in terms of feed, in recent years, also gradually big as the water duckweed of traditional Chinese medicine ingredients Family is known, carries out the extraction and exploitation of traditional Chinese medicine ingredients, it has now been found that, water duckweed be applied to hypotensive in terms of research report Road product occur again and again, and result is shown according to the study, play the role of conspicuousness at hypoglycemic aspect.Find according to the study, water duckweed is in drop Research in terms of blood glucose there are no document report, and specifically the research mechanism of action is not yet clear, requires study.

6）, root of Chinese trichosanthes be cucurbitaceous plant root, be a herb composition, containing abundant amino acid, have with various Composition is imitated, specific effect has clearing heat-fire, promoted the production of body fluid to quench thirst, apocenosis detumescence.Substantial amounts of research shows that root of Chinese trichosanthes is moved to later period of hepatocarcinoma Planting ascites tumor, liver-cancer solid tumor, the tumour cell of in vitro culture has obvious therapeutic effect, at the same to immunological regulation, antibacterial, Antivirus action plays the role of good, current root of Chinese trichosanthes application a lot of on document report of the root of Chinese trichosanthes in the studies above Investigation on hypoglycemic is fewer, and pertinent literature is not reported.

7）, it is pink be being collectively referred to as by the different article of peach kernel and safflower, peach kernel is the seed of rosaceous plant, and itself can make For food, it can also be used as Chinese medicine, the sweet flat, bitter of peach kernel enters lung, liver, large intestine channel；There is promoting blood circulation, relax bowel Effect, peach kernel has extraordinary health-care efficacy in the traditional Chinese medical science, all has certain therapeutic action, such as dissolving stasis for many diseases Blood effect, antiinflammatory action, anti-allergic effects etc..Safflower is a Chinese medicine, warm-natured, pungent, the thoughts of returning home, Liver Channel, have invigorate blood circulation, Blood stasis removing analgesic, for Amenorrhea, dysmenorrhoea, traumatic injury effect, also have active muscles and bones, the effect stimulated circulation.In addition, red Flower also has functions that beautifying face and moistering lotion, can adjust hormonal balance, toxin-expelling and face nourishing etc..It is pink as traditional Chinese medicine ingredients, it is warm-natured, have Promoting blood circulation and removing blood stasis, effect of nourshing blood and promoting blood circulation can be used for disease caused by cardiovascular and cerebrovascular blood supply insufficiency, and various blood stasis.For sugar The adjoint chronic complicating diseases of urine disease have good preventive and therapeutic action.

8）, natto be that soybean forms through fermenting bacillus subtilis, also referred to as Bacillus natto, in the viscous substance of natto and its surrounding Containing Multiple components, for example, protease, multivitamin, gamma glutamyl transpeptidase, alpha-polyglutamic acid etc., in recent years Research is found, with many physiological functions, with the effect such as hypotensive, antitumor, inoxidizability, thrombus dissolving.Exist in natto A kind of enzyme with very strong thrombolytic effect is referred to as Nattokinase, there is good curative effect to cerebral thrombus, coronary heart disease, myocardial infarction etc., There are obvious treatment and prevention to act on the chronic complicating diseases that diabetes trigger, at present, China to the research of Nattokinase increasingly Increase, importance of the Nattokinase in terms of medical science.

9）, the leaf that ginkgo leaf is Ginkgoaceae plant Ginkgo biloba, flavonoids, terpene lactones and a small amount of are contained in ginkgo leaf The main chemical compositions such as Polyphenols, alkaloid, long-chain alcohol, ketone and trace element.A lipidated conjunction present in ginkgo leaf Thing, it is to maintaining liver function and promoting hematopoiesis function to play an important role；Ginkgo biloba p.e Central nervous system has protection to make With, play the role of improve nerve modulation, antioxidation.Domestic and foreign scholars are entered to chemical composition, pharmacologic action of ginkgo leaf etc. Numerous studies are gone, it was confirmed that ginkgo leaf is in treatment cardiovascular and cerebrovascular disease, increase coronary blood flow, expansion blood vessel, reduction Blood pressure, improve serum cholesterol and phosphide ratio play the role of it is good, while in treatment cerebral ischemia, brain aging, senile dementia There is good curative effect in terms of disease and diabetes.

10）, leech be traditional Chinese medicine simply, treatment hemostasis, the card of water knot, it is shown that its unique curative effect.Hirudin is The active component extracted from the saliva of Hementaria officianalis, hirudin, which is first, is used for the anticoagulant of the mankind, and hirudin has Blood coagulation resisting function, inhibiting effect on tumor metastasis treats unstable angina, acute myocardial infarction, postangioplasty thrombus shape Into, haemodialysis, extracorporal circulatory system, disseminated intravascular coagulation etc., its effect is substantially better than heparin etc., and no-rod tractor is induced Platelet reducing disease and thrombus complex into sequelae such as, renal failures.Hirudin is again non-toxic, no obvious antigenicity, in reasonable agent In amount, the danger not caused bleeding, therefore it is by the new class medicine as preventing and treating thrombus disease, with very big society Benefit and economic benefit.

The diabetes of insulin-resistant can be treated, active ingredient compounding is than single component to prevention and treatment diabetes Effect more preferably, but also can prevent and treat some chronic complicating diseases extremely adjoint with blood glucose rise；Present invention production work Skill is simple, cost is low, high efficiency, economic benefit, social benefit are notable.

Embodiment

A kind of pharmaceutical composition for preventing and treating diabetes and its complication, its drug regimen composition composition：Sea cucumber polypeptide, brown alga Oligosaccharides, kudzu root extract, water Herba Spirodelae extract, Radix Trichosanthis extract, pink extract, ginkgo biloba p.e, hirudin and receive Beans kinases.

Embodiment 1

Sea cucumber polypeptide, kudzu root extract, brown alga oligose, water Herba Spirodelae extract, Radix Trichosanthis extract, pink extraction in the present embodiment The preparation method of thing, ginkgo biloba p.e, by 1kg Mass Calculations.

1kg sea cucumbers are weighed, cleans, removes internal organ, plus 600mL pigment are broken, plus 1% neutral proteinase（Quality of sea cucumber）, 50 DEG C 10h is digested, concentration, alcohol precipitation, separation, spray drying obtains refined sea cucumber Gly-His-Lys, standby.

The fresh sea-tangles of 1kg are weighed, are rinsed, are crushed, in 0.1mol/L hydrochloric acid, 1.5mLHCHO stirs 1h at room temperature, are filtered, filter Slag adds 60 DEG C of stirring 1h of 1%Na2CO3, and centrifuging and taking supernatant, concentration, ethanol precipitation obtains sodium alginate crude product, dropped by enzyme Solution, alkali are neutralized, ethanol precipitation sodium alginate crude product, obtain brown alga oligose crude product, brown alga oligose fine work is obtained by gel filtration, Vacuum drying obtains brown alga oligose freeze-dried powder, standby.

The 1kg roots of kudzu vine are weighed, are cleaned, are dried, crushes, is dissolved in water, 1.5% cellulase is added（Root of kudzu vine quality）, 48 DEG C Lower degraded 8-10h, concentration, plus ethanol are extracted（It is repeated 3 times）, spray drying obtains kudzu root extract powder, standby.

1kg water duckweeds are weighed, are cleaned up, 2L distilled water is added, reflow treatment is carried out, flowed back 2-3 times, one time 1-2 is small When, filtering and concentrating obtains water Herba Spirodelae extract.

1kg roots of Chinese trichosanthes are weighed, cleaning, drying, crushing add 2L distilled water, carry out reflow treatment, flow back 2-3 times, once 1-2 hours, filtering and concentrating obtained water Herba Spirodelae extract.

1kg roots of Chinese trichosanthes are weighed, cleaning, drying, crushing add 2L distilled water, carry out reflow treatment, flow back 2-3 times, once 1-2 hours, filtering and concentrating obtained water Herba Spirodelae extract.

Peach kernel and safflower 1kg are weighed, is extracted 2-3 times with 60-90% alcohol refluxs, each 1-2 hours, merging filtrate, is reclaimed Ethanol, is concentrated, and is dried, is obtained pink extract.

Ginkgo leaf 1kg is weighed, is extracted 2-3 times with 30-60% alcohol refluxs, each 1-2 hours, merging filtrate, second is reclaimed Alcohol, is concentrated, and is dried, is obtained ginko leaves flavone class extract.

According to said extracted method, sea cucumber polypeptide, kudzu root extract, brown alga oligose, water Herba Spirodelae extract, root of Chinese trichosanthes are weighed Extract, pink extract, ginkgo biloba p.e, hirudin and Nattokinase stir, and are dissolved in water, and mouth is made in seasoning Liquid type is taken, that is, obtains the pharmaceutical composition of the present invention of oral liquid type.

Embodiment 2：

The daily food ration of hyperglycemia animal that pharmaceutical composition in the present embodiment is induced streptozotocin, the influence of body weight.

Kunming 40 mouse of kind SPF levels are taken, male and female half and half, fasting 12h, free water, high glucose and high fat Combined fodder is multiple The streptozotocin 80mg/kg of few dosage（Complete within 30 minutes）Modeling, raises fasting after 7d（It can't help water）After 4h, tail vein is taken, Blood glucose is surveyed, blood glucose value models successfully animal in 10~25mmol/L for blood glucose, be randomly divided into 4 groups, model control group, the positive are right According to group（Metformin hydrochloride tablet）, hypoglycemic medicine combination group, pharmaceutical composition+positive group, it is normal separately to take 10 normal mouses After group, successive administration 35d, the food ration and body weight value added on products of mouse are measured.

The influence of hyperglycemia animal food ration, body weight that the pharmaceutical composition of the present invention of table 1 is induced streptozotocin（`x ±s）

Group	Take in appetite（g/d）	Increased weight（g）
			Normal group	4.12±0.08	11.67±0.67
Model control group	3.48±0.23	24.45±0.88##
			Positive controls	3.42±0.20	18.32±0.56**
Composition group	3.43±0.24	20.32±0.75*
			Composition+positive group	3.40±0.12	16.14±0.78**☆

Note：#p≤0.05, ##p≤0.01 and normal group ratio；* p≤0.05, * * p≤0.01 and model control group ratio；☆p≤ 0.05, ☆ ☆ p≤0.01 and positive controls ratio.

From the data display of table 1, the increased weight of model control group mouse is apparently higher than control group（p≤0.01）, take the photograph Appetite change is not notable.Compared with model control group, composition A groups and composition+positive group weight increment difference are significant Reduce 16.8% and 33.9%.Compared with positive controls, composition+positive group Mice Body mass weight gain reduces 20.5%.Knot Fruit shows that natural drug composition can suppress the increase of mouse weight, reduce the obesity of mouse, composition and hydrochloride Biguanides piece compounding use, effect is more notable.

Embodiment 3：

Hyperglycemia animal fasting blood-glucose, serum insulin and pancreas that the hypoglycemic medicine composition of the present embodiment is induced streptozotocin The influence of insulin resistance index.

The Kunming mouse 40 for choosing male and female half and half is modeled with 80mg/kg streptozotocins, selects blood glucose modeling successful Mouse, is randomly divided into 4 groups, model control group, positive controls（Melbine）, medicine group is charge-coupled, drug regimen+positive group, Select 10 normal mouse else to be set to after Normal group, successive administration 35d, fasting blood-glucose is determined using blood glucose meter, mouse is empty After 3~5h of abdomen, afterbody blood is taken；Eyeball blood is taken, serum is routinely separated, serum insulin is determined with reference to ELISA kit method Content；And according to formula（1）Calculate insulin resistance index（Insulin resistance index, HOMA-IR）.

HOMA-IR=serum insulin level × fasting blood glucose level/22.5 (1)

Hyperglycemia animal fasting blood-glucose that the hypoglycemic medicine composition of the present invention of table 2 is induced streptozotocin, serum insulin and The influence of insulin resistance index（`x ±s）

Group	Fasting blood-glucose mmol/L	Serum insulin mU/L	HOMA-IR
				Normal group	9.28±1.0	10.86±0.32	4.53±0.32
Model control group	13.12±0.82##	14.68±0.60##	8.53±0.86##
				Positive controls	10.93±0.69**	13.32±0.54*	5.80±1.21*
Pharmaceutical composition group	11.02±0.65*	13.54±0.15*	5.66±1.38*
				Composition+positive group	10.04±0.72**	11.30±0.56**☆	4.82±1.22**

Note：#p≤0.05, ##p≤0.01 and normal group ratio；* p≤0.05, * * p≤0.01 and model control group ratio；☆p≤ 0.05, ☆ ☆ p≤0.01 and positive controls ratio.

Hyperglycaemia and high insulin levels are the features of diabetes B, and such as table 2 is known, model control group and Normal group Compare, fasting blood-glucose, serum insulin and HOMA-IR have the influence of conspicuousness（p≤0.01）.Compared with model control group, Pharmaceutical composition group fasting blood-glucose, serum insulin and HOMA-IR have dropped 16%, 7.7% and 33.6% respectively, and pharmaceutical composition+ Positive group fasting blood-glucose, serum insulin and HOMA-IR have dropped 23.4%, 23.1% and 43.4% respectively.With positive controls ratio Compared with fasting blood-glucose and HOMA-IR changes be not notable, and serum insulin level reduces 15.1%.As a result show：Composition can change The insulin resistance of kind mouse, the effect of composition+metformin hydrochloride tablet compounding is more preferable.

Embodiment 4：The shadow for the hyperglycemia animal sugar tolerance that the hypoglycemic medicine composition of the present embodiment is induced streptozotocin Ring.

Choose after 40 successful Kunming mouses of modeling, successive administration 35d, water 5h is can't help in mouse fasting, takes afterbody blood, Blood sugar level is determined using blood glucose meter.20min gavage glucose（2.0g/kg）Solution, determine respectively to 0h after glucose, 0.5h, 2h blood glucose value, by formula（2）And calculate Area under the curve of blood glucose（Area under the curve, AUC）.

AUC=0.25 × 0h blood sugar concentration+0.5h blood sugar concentration+0.75 × 2h blood sugar concentrations（2）

The influence for the hyperglycemia animal sugar tolerance that the hypoglycemic medicine composition of the present invention of table 3 is induced streptozotocin（`x ±s）

Group	AUC(h•mmol/L)
		Normal group	21.65±0.55
Model control group	30.23±0.55##
		Positive controls	26.33±0.88**
Pharmaceutical composition group	27.69±0.45*
		Pharmaceutical composition+positive group	23.12±0.34**☆

Note：#p≤0.05, ##p≤0.01 and Normal group ratio；* p≤0.05, * * p≤0.01 and model control group ratio；☆p ≤ 0.05, ☆ ☆ p≤0.01 and positive controls ratio

Glucose tolerance is inversely proportional with AUC, as shown in Table 3, is compared with Normal group, model control group mouse it is sugared water-fast Dawn is aobvious impaired.Compared with model control group, taken after hypoglycemic medicine composition, AUC have dropped 8.4%, drug administration combination After thing+metformin hydrochloride tablet, AUC have dropped 23.5%.Compared with positive controls, AUC change of the drug regimen without group mouse Not substantially, the AUC of composition+metformin hydrochloride tablet group mouse has the influence of conspicuousness, reduces 12.1%.Thus data show Show, hypoglycemic medicine composition and metformin hydrochloride tablet compounding use are best to blood sugar decreasing effect.

Embodiment 5：Hyperglycemia animal fasting blood-glucose and blood that the present composition is induced streptozotocin with single component The comparison of clear insulin

120 Kunming mouses are selected, male and female half and half, fasting 12h, free water, high glucose and high fat Combined fodder repeatedly lacks dosage Streptozotocin 80mg/kg（Complete within 30 minutes）Modeling, raises fasting after 7d（It can't help water）After 4h, take tail vein to survey blood glucose, build Mould success mouse is randomly divided into 12 groups, model control group, positive controls（Metformin hydrochloride tablet）, sea cucumber polypeptide group, the root of kudzu vine Extract group, brown alga oligose group, pharmaceutical composition group, water Herba Spirodelae extract group, Radix Trichosanthis extract group and pink extract group, After ginkgo biloba p.e group, hirudin group, Nattokinase group, successive administration 35d, fasting blood-glucose is determined using blood glucose meter, mouse On an empty stomach after 3~5h, afterbody blood is taken；Eyeball blood is taken, serum is routinely separated, serum islet is determined with reference to ELISA kit method The content of element.

Hyperglycemia animal fasting blood-glucose and serum pancreas that the present composition of table 4 is induced streptozotocin with single component The comparison of island element（`x ±s）

Group	Fasting blood-glucose mmol/L	Serum insulin mU/L
			Model control group	14.67±0.38	16.88±0.62
Positive controls	12.75±0.88**	13.56±0.46**
			Sea cucumber polypeptide group	14.10±0.69☆	16.13±0.44☆☆
Kudzu root extract group	14.09±0.67☆	16.22±0.47☆☆
			Brown alga oligose group	14.14±0.89☆	15.86±0.77☆☆
Water Herba Spirodelae extract	14.42±0.58☆	16.65±0.38☆☆
			Radix Trichosanthis extract	14.47±0.95☆	16.14±1.02☆☆
Pink extract	14.56±0.77☆	16.35±0.87☆☆
			Ginkgo biloba p.e group	14.38±0.44☆	16.15±0.99☆☆
Hirudin group	14.58±0.14☆	16.86±0.10☆☆
			Nattokinase group	14.88±0.67☆	16.79±0.56☆☆
Pharmaceutical composition group	8.02±0.12**☆☆	10.45±0.55**☆☆

Note：* p≤0.05, * * p≤0.01 and model control group ratio；☆ p≤0.05, ☆ ☆ p≤0.01 and positive controls Than.

As seen from the results in Table 4, compared with model control group, positive controls have a significant impact（p≤0.01）, fasting blood Sugar and serum insulin reduce 13.2% and 19.6% respectively, and sea cucumber polypeptide group, kudzu root extract group, brown alga oligose group, water are floated Duckweed extract group, Radix Trichosanthis extract group, pink extract group, ginkgo biloba p.e group, hirudin group and Nattokinase group are empty Abdomen blood glucose and serum insulin change be not notable, and pharmaceutical composition group fasting blood-glucose and serum insulin have dropped 45.3% respectively With 38.1%.Compared with positive controls, sea cucumber polypeptide group, kudzu root extract group, brown alga oligose group, water Herba Spirodelae extract group, day Pollen extract group, pink extract group, ginkgo biloba p.e group, hirudin group and Nattokinase group fasting blood-glucose and serum pancreas Island element level is all higher than each level of positive group, and pharmaceutical composition fasting blood-glucose and serum insulin have a significant impact, and have dropped 36.9% and 22.9%.This result shows that than single component effect very well, treatment is with preventing diabetes for pharmaceutical composition of the invention And complication effect is more preferable.

Protection scope of the present invention is not limited merely to above-described embodiment, and all technical schemes belonged under thinking of the present invention are equal Belong to protection scope of the present invention.It should be pointed out that for those skilled in the art, not departing from the present invention Some improvements and modifications under the premise of principle, these improvements and modifications also should be regarded as protection scope of the present invention.

Claims (6)

1. a kind of pharmaceutical composition for preventing and treating diabetes and its complication, it is characterised in that：Its drug regimen composition is constituted：Sea cucumber Polypeptide, brown alga oligose, kudzu root extract, water Herba Spirodelae extract, Radix Trichosanthis extract, pink extract, ginkgo biloba p.e, water Leech element and Nattokinase.

2. a kind of pharmaceutical composition for preventing and treating diabetes and its complication according to claim 1, it is characterised in that：Its medicine The weight ratio of thing combination ingredient is：0.5-1.5 parts of sea cucumber polypeptide, 2-3 parts of brown alga oligose, 3-4 parts of kudzu root extract, water duckweed carries Take 4-6 parts of thing, 4-6 parts of Radix Trichosanthis extract, pink extract 4-6 parts, 3-4 parts of ginkgo biloba p.e, hirudin 0.1-0.5 Part, 1-2 parts of Nattokinase.

3. a kind of pharmaceutical composition for preventing and treating diabetes and its complication according to claim 2, it is characterised in that：It is described Brown alga oligose is by enzymolysis, alcohol precipitation, filtering, concentration, the small molecule monose for refining and being made by fresh sea-tangle.

4. a kind of pharmaceutical composition for preventing and treating diabetes and its complication according to claim 2, it is characterised in that：It is described Pink extract is the pink extract as obtained by peach kernel, safflower are extracted through alcohol reflux.

5. a kind of pharmaceutical composition for preventing and treating diabetes and its complication according to claim 2, it is characterised in that：Its medicine The weight ratio of thing combination ingredient is：1 part of sea cucumber polypeptide, 2 parts of brown alga oligose, 3 parts of kudzu root extract, water Herba Spirodelae extract 4 part, day 4 parts of pollen extract, 4 parts of pink extract, 3 parts of ginkgo biloba p.e, 0.2 part of hirudin, 2 parts of Nattokinase.

6. a kind of pharmaceutical composition for preventing and treating diabetes and its complication according to claim 2, it is characterised in that：It is made Preparation Method is as follows：

1）, sea cucumber with 1-2% neutral proteinases degrade 8-10h, 50-70% ethanol extract 2-3 time, it is each 2-3 hour, filtering, conjunction And filtrate, ethanol is reclaimed, ethanol extract is obtained, concentrated, dries, obtains sea cucumber polypeptide extract；

2）, the root of kudzu vine with 1.5-2% cellulase degradations 8-10h, 50-70% ethanol extract 2-3 time, it is each 2-3 hour, filtering, conjunction And filtrate, concentrate, dry, obtain kudzu root extract；

3）, fresh sea-tangle with 1.5-2% enzymes degrade 10-12h, 60-70% ethanol extract 2-3 time, it is each 2-3 hour, filtering, merging filter Liquid, reclaims ethanol, obtains ethanol extract, concentrates, and dries, obtains brown alga oligose extract；

4）, water duckweed extracted 2-3 time with 30-60% ethanol, ethanol extract is reclaimed in each 2-3 hour, filtering, and concentration is dry, Obtain water Herba Spirodelae extract；

5）, root of Chinese trichosanthes with 30-90% alcohol refluxs extract 2-3 time, it is each 2-3 hour, filtering, merging filtrate, concentrate, drying, obtain To Radix Trichosanthis extract；

6）, peach kernel and safflower extracted 2-3 time with 60-90% alcohol refluxs, each 1-2 hours, merging filtrate, recovery ethanol is dense Contracting, dries, obtains pink extract；

7）, ginkgo leaf extracted 2-3 time with 30-90% alcohol refluxs, each 2-3 hour, filtering, revolving ethanol is concentrated, dry Ginkgo biloba p.e；

8）, leech in the physiological saline of 10 multiple doses, extract in two times at 70 DEG C, each 30min, obtain preferable hirudin；

9）, in the inoculation that separates from natto to fluid nutrient medium, incubated at 37 ± 1 DEG C, centrifuging and taking Supernatant, obtains Nattokinase crude extract；

10）, choose 1 portion of sea cucumber polypeptide, 2 portions of brown alga oligoses, 3 portions of kudzu root extracts, 4 portions of water Herba Spirodelae extracts, 4 portions of roots of Chinese trichosanthes carry Thing, 4 parts of pink extracts, 3 parts of apricot leaf extracts, 0.2 part of hirudin, 2 parts of Nattokinases are taken, then choose 1.5 parts of citric acids, 3 Part radix glycyrrhizae and 12 parts of white granulated sugar mixed dissolutions, deodorization seasoning allotment oral formulations.