CN1559539A - Medicinal mixture possessing alpha glycocidase inhibiting activity and its use - Google Patents
Medicinal mixture possessing alpha glycocidase inhibiting activity and its use Download PDFInfo
- Publication number
- CN1559539A CN1559539A CNA2004100186774A CN200410018677A CN1559539A CN 1559539 A CN1559539 A CN 1559539A CN A2004100186774 A CNA2004100186774 A CN A2004100186774A CN 200410018677 A CN200410018677 A CN 200410018677A CN 1559539 A CN1559539 A CN 1559539A
- Authority
- CN
- China
- Prior art keywords
- mori
- alpha
- extract
- pharmaceutical composition
- glucosidase inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 230000002401 inhibitory effect Effects 0.000 title description 4
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- 229930003944 flavone Natural products 0.000 claims abstract description 34
- 235000011949 flavones Nutrition 0.000 claims abstract description 34
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 claims abstract description 34
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- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 16
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims description 73
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- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 claims description 36
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- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims description 36
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- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 claims description 34
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- 239000012141 concentrate Substances 0.000 claims description 6
- NEKNNCABDXGBEN-UHFFFAOYSA-L disodium;4-(4-chloro-2-methylphenoxy)butanoate;4-(2,4-dichlorophenoxy)butanoate Chemical compound [Na+].[Na+].CC1=CC(Cl)=CC=C1OCCCC([O-])=O.[O-]C(=O)CCCOC1=CC=C(Cl)C=C1Cl NEKNNCABDXGBEN-UHFFFAOYSA-L 0.000 claims description 6
- AIFCFBUSLAEIBR-UHFFFAOYSA-N ginkgetin Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C(C=1)=CC=C(OC)C=1C1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=C(O)C=C1 AIFCFBUSLAEIBR-UHFFFAOYSA-N 0.000 claims description 6
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Images
Abstract
A medicine with high activity to suppress alpha-glucosidase for treating diabetes, and hyperlipemia, and delaying sanility contains the common alkaloid extracted from mulberry plants and the flavone extract.
Description
Technical field:
The present invention relates to a kind of medical composition and its use, particularly relate to a kind of pharmaceutical composition and application on the preparation hypoglycemic medicine thereof with alpha-glucoside inhibiting activity.
Background technology:
Diabetes (Diabetes Mellitus) are that a group of being caused by hypoinsulinism and/or impaired insulin action is the metabolic disease of feature with the hyperglycemia.It shows as, and concentration of glucose raises unusually in blood and the urine, blood glucose, can occur typical " three-many-one-little " symptom when glucose in urine is too high, i.e. polydipsia, polyuria, polyphagia and lose weight, and with fatigue and weak.The traditional Chinese medical science claims that diabetes are " diabete ", is meant that with excessive thirst taking fluids profusely, rapid digestion of food and polyorexia, frequent micturition, emaciated physique be the disease of feature.Diabetes generally are divided into several types such as type 1 diabetes, type 2 diabetes mellitus and gestational diabetes.Type 2 diabetes mellitus was called non-insulin-dependent diabetes mellitus in the past, accounted for 90% of diabetic sum.Along with growth in the living standard, the development of the prolongation of life expectancy and diabetes detection means, the prevalence of countries in the world diabetes is all raising.The oral drugs of treatment type 2 diabetes mellitus mainly divide four big class, i.e. sulfonylurea, biguanides, alpha-glucosidase inhibitor and euglycemic agents.Alpha-glucosidase inhibitor (being alpha-glucosidase inhibitor) is a class new oral antidiabetic drug, is applicable to the diabetes of any kind.The alpha-glucosidase inhibitor that has been approved at present the clinical diabetes treatment mainly contains 3 kinds: acarbose (acarbose), voglibose (voglibose) and miglitol (miglitol), they all are nitrogenous alkaloids.
The digestion of carbohydrate in the food in gastrointestinal tract is the result of the enzymatic reaction of several successive.The pancreas α-Dian Fenmei partial hydrolysis that starch at first is positioned at duodenum and jejunum top is the molecular weight smaller oligosaccharides, as maltose, dextrinose and α-restricted glucosan etc.These oligosaccharide are difficult to be absorbed by mucous membrane of small intestine, must be hydrolyzed to monosaccharide such as glucose through maltase, glucoamylase and isomaltase, could be entered metabolic cycles by the effective transportation of mucomembranous surface.Sucrose in the food then is hydrolyzed to fructose and glucose by saccharase.These enzymes are referred to as alpha-glucosidase, are positioned at intestinal epithelial cell brush edge place.Under the normal condition, digesting and assimilating of carbohydrate mainly occurs in upper part of small intestine, and the position that small intestinal is lower (ileum) do not participate in this process.This is that the small intestinal bottom does not have the substrate of enzyme effect because the carbohydrate major part is digested and absorbs at upper part of small intestine, and its alpha-glucosidase effect is very faint.
Because nitrogen is contained in the active center of alpha-glucosidase inhibitor, can combine with the binding site of carbohydrate on the alpha-glucosidase, its affinity is much larger than the normal substrate of enzyme, therefore, when after meals are taken food, alpha-glucosidase inhibitor can be brushed the edge place at intestinal epithelial cell and compete mutually with oligosaccharide, occupies oligosaccharide binding site on the alpha-glucosidase, digesting and assimilating of oligosaccharide is obstructed, reduces the digestion of oligosaccharide at upper part of small intestine.The carbohydrate that is not digested is transported to hypomere and colon in the small intestinal, causes digesting and assimilating of carbohydrate to occur in the whole section small intestinal, the absorption that delays and prolonged GLPP, thus reduce increasing of post-prandial glycemia.
Is the blood sugar lowering new approaches of rising after the seventies in 20th century with alpha-glucosidase inhibitor as hypoglycemic medicine, and its screening and development start from states such as Germany and Japan.People extract a series of alpha-glucosidase mortifier at first from actinomyces and streptomyces, the common ground of these mortifiers on chemical constitution is to contain by a part cyclohexanhexanol and a part amino sugar (4,6-dideoxy-4-amino-D-glucose) active center of Zu Chenging is called acarviosine.Confirmed that (deoxynojirimycin DNJ) has good inhibition effect to glycosidase to the 1-deoxynojirimycin, 1-deoxynojirimycin chemistry 2R by name the eighties, 3R, 4R, 5S-2-methylol-3,4,5-trihydroxy piperidines, this alkaloid are a kind of analogs of natural sugar.
Other discovers that most Flavonoid substances have significant alpha-glucosidase inhibitor activity, as having 6 kinds of flavonols materials to have the effect of significant inhibition alpha-glucosidase in Cupid's wood leaf, it is to suppress the active component of alpha-glucosidase that 3 kinds of flavonoid glycoside are arranged in the Folium Ziziphi Spinosae, separate the inhibition composition obtained 5 kinds of alpha-glucosidases in the extract of Cortex Eucommiae tea, and according to its physicochemical characteristic and
13CNMR result determines that chemical constituent is the quercetin derivative of Flavonoid substances.It is reported that tea polyphenols has blood sugar reducing function to the inductive diabetes rat of chain urea assistant streptavidin, its hypoglycemic mechanism may be that tea polyphenols is a glycosidase inhibitor, and the decomposition of sucrose and starch is delayed, thereby reduces the rising of blood glucose behind oral sucrose and the starch.
Flavone compound is the compounds that occurring in nature extensively exists, and with more in the plants such as pulse family, Rutaceae, Labiatae, Compositae, often exists with free state or with form that sugar is combined into glycoside in plant.As the crude drug Flos Sophorae Immaturus, Pericarpium Citri Reticulatae, Radix Puerariae, Radix Scutellariae, Semen Ginkgo, Radix Glycyrrhizae, Flos Chrysanthemi, fly water Ji etc. and all contain flavone component, quercitrin, globulariacitrin (rutin), hesperidin, puerarin, big legumin, ginkgetin, baicalin, fly water silibin etc. and have functions such as the cardiovascular of adjusting and antiinflammatory, equal permeability of scalable blood capillary to a certain extent, thus delay the rising of post-prandial glycemia.
Chinese patent application number 01113191.8 discloses " Chinese medicine extract, Preparation Method And The Use with alpha-glucosidase inhibitor activity ", this patent has related to from the total alkaloids of Chinese medicine Cortex Mori, Folium Mori and Fructus Mori preparation, the Preparation method and use that does not relate to the flavonoid alpha-glucosidase inhibitor, more do not relate to above-mentioned alkaloids substance and flavone compound and unite use, make the obvious enhanced report of alpha-glucosidase inhibitor effect.
China's natural resources of Chinese medicinal materials is abundant, from the digestion of sugar, absorbs again, and metabolic pathway is started with, and explains traditional Chinese medical science mechanism with modern medical theory, develops safe and reliablely, and effective ingredient is clear and definite, and the natural clearly hypoglycemic medicine of action target provides a new approach.
Summary of the invention:
The purpose of this invention is to provide a kind of pharmaceutical composition with alpha-glucosidase inhibitor activity;
Another object of the present invention provides a kind of pharmaceutical composition with alpha-glucosidase inhibitor activity and treats diabetes, treatment hyperlipidemia, the application in antioxidation, the antidotal medicine in preparation.
Technical scheme of the present invention is summarized as follows:
A kind of pharmaceutical composition with alpha-glucosidase inhibitor activity, at least a by the total alkaloids that extracts from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, percentage by weight is 5～90%, flavone extract, percentage by weight is 10～95% to form.
The total alkaloids that extracts from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori is prepared by following method: with Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, after crushed, with the acid of water or 0.01～0.1N or methanol or ethanol or aqueous alcohols serves as to extract solvent, carry out merceration extraction or heating extraction or reflux, extract,, the volume that extracts quantity of solvent is to be extracted 5～15 times of decoction pieces weight, repeats to extract 1-4 time; Remove by filter medicinal residues; Filtrate concentrates; Add ethanol precipitation, remove contamination precipitation; Through centrifugal or filtration, remove residue; Cation exchange resin on the supernatant is washed non-adsorbable to the greatest extent impurity with deionized water, is 0.2-1N ammonia eluting with concentration; The eluent concentrating under reduced pressure is removed ammonia; Through the activated carbon adsorption decolouring, collect destaining solution; Concentrate, make the powdered total alkaloids.
The total alkaloids that from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, extracts, percentage by weight preferably 30～80%, flavone extract, percentage by weight preferably 20～70% is formed.
Described flavone extract can select a kind of in catechin, Quercetin, the tea polyphenols.
Flavone extract also can select two kinds in catechin, Quercetin, the tea polyphenols, and wherein, catechin: Quercetin: the weight ratio of tea polyphenols is 0: 1～9: 1～9 or 1～9: 0: 1～9 or 1～9: 1～9: 0.
Flavone extract can also be totally three kinds of catechin, Quercetin, tea polyphenols, and catechin: Quercetin: the weight ratio of tea polyphenols is 1～9: 1～9: 1～9.
Flavone extract can also be quercitrin, globulariacitrin, hesperidin, puerarin, big legumin, ginkgetin, baicalin, it is at least a, two or more to fly in the water silibin, can be by any part by weight combination.
The total alkaloids that from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, extracts, it can be a kind of total alkaloids in above-mentioned several prepared slices of Chinese crude drugs as extracting in Bombyx mori L. or Ramulus Mori or Cortex Mori or the Folium Mori, also can be two kinds, as the mixture of the total alkaloids that from Bombyx mori L. and Ramulus Mori, extracts, it also can be three kinds or four kinds.
Employed cation exchange resin is the strong acid type resin of crosslinked polystyrene system in the preparation process of the total alkaloids that extracts from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, its model is 001 * 1.1 or 001 * 4 or 001 * 7 or 001 * 14.5 or Amberlite IR120 or Dowex 50 or Zerolit 225, and the eluent ammonia concn is advisable with 0.5N.
A kind of have the pharmaceutical composition of alpha-glucosidase inhibitor activity in preparation treatment diabetes, treatment hyperlipidemia, the application in antioxidation, the antidotal medicine.
The present invention starts with from the mechanism of alpha-glucosidase inhibitor, filters out several different types of structure alpha-glucosidase inhibitor compositions from Chinese medicine; A kind of is total alkaloids composition in moraceae plants medical material (Ramulus Mori, Cortex Mori, Folium Mori) or the Bombyx mori L., and it can effectively suppress the hydrolysis of oligosaccharide.Another kind of is flavone extract, it can be the glycoside unit of free state, also can be and the bonded glycoside of sugar, as: catechin, Quercetin, tea polyphenols, puerarin, big legumin, fly water silibin, hesperidin, quercitrin, globulariacitrin (rutin), ginkgetin, baicalin etc., the inhibition effect of comparing its alpha-glucosidase with the first kind a little less than, but effect is arranged, and the penetrating amount that can reduce the small intestinal blood capillary has suppressed the absorption of glucose effectively with the small intestinal glucose transport; The two associating result of use is remarkable, has good synergism, can suppress and delay the digestion and the absorption of carbohydrate in the food effectively, and hypoglycemic effect is better than total alkaloids and the independent effect of using of flavone extract.
The total alkaloids that the present invention extracts from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, and the pharmaceutical composition of forming with flavone extract, and utilize various known drug preparation techniques by this pharmaceutical composition, the various preparations of making: comprise tablet, capsule, granule, powder, drop pill etc., it is clear to have the mechanism of action, determined curative effect can be used for treating diabetes, obesity, hyperlipidemia, and antioxidation, antidotal pharmacologically active are arranged.
Description of drawings:
Fig. 1 suppresses curve chart for the alpha-glucosidase of the total alkaloids, catechin, Quercetin and the tea polyphenols that extract from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori;
Fig. 2 unites the alpha-glucosidase inhibition design sketch of use for Ramulus Mori total alkaloids and catechin, Quercetin, tea polyphenols.
The specific embodiment:
The present invention is further illustrated below in conjunction with specific embodiment, but do not limit the present invention in any way.
Table 1:
| The embodiment number | Total alkaloids (unit: gram) | Flavone extract | ||
| First kind of (unit: gram) | Second kind of (unit: gram) | The third (unit: gram) | ||
| | | Quercetin 90 | ||
| Embodiment 2 | Extract 5 in the Bombyx mori L. | Catechin 95 | ||
| Embodiment 3 | Extract 30 in the Bombyx mori L. | Tea polyphenols 70 | ||
| Embodiment 4 | Extract 50 in the Bombyx mori L. | Quercetin 5 | Tea polyphenols 45 | |
| Embodiment 5 | | Quercetin 81 | Tea polyphenols 9 | |
| Embodiment 6 | Extract 80 in the Ramulus Mori | Quercetin 10 | | |
| Embodiment 7 | Extract 5 in the Ramulus Mori | Catechin 47.5 | Tea polyphenols 47.5 | |
| Embodiment 8 | | Catechin 9 | Tea polyphenols 81 | |
| Embodiment 9 | Extract 50 in the Folium Mori | Catechin 45 | Tea polyphenols 5 | |
| | Extract 90 in the Folium Mori | Catechin 1 | Quercetin 9 | |
| Embodiment 11 | Extract 20 in the Cortex Mori | Catechin 72 | Quercetin 8 | |
| Embodiment 12 | | Catechin 30 | Quercetin 30 | Tea polyphenols 30 |
| Embodiment 13 | Extract in 20 Bombyx mori L.s in the Folium Mori and extract 23 | Catechin 3 | Quercetin 27 | Tea polyphenols 27 |
| Embodiment 14 | Extract in 13 Bombyx mori L.s in the Ramulus Mori and extract 30 | Catechin 27 | Quercetin 3 | Tea polyphenols 27 |
| Embodiment 15 | Extract in the Folium Mori to extract in 10 Bombyx mori L.s in 10 Ramulus Moris and extract 23 | Catechin 27 | Quercetin 27 | Tea polyphenols 3 |
| Embodiment 16 | Extract in the Folium Mori to extract in 10 Ramulus Moris to extract in 10 Cortex Mori in 10 Bombyx mori L.s and | Catechin 20 | Quercetin 20 | Tea polyphenols 20 |
| Embodiment 17 | | Quercitrin 90 | ||
| Embodiment 18 | Extract 5 in the Bombyx mori L. | Globulariacitrin 95 | ||
| Embodiment 19 | Extract 30 in the Bombyx mori L. | Hesperidin 30 | ||
| Embodiment 20 | Extract 50 in the Bombyx mori L. | Quercitrin 25 | Hesperidin 25 | |
| Embodiment 21 | | Puerarin 90 | ||
| Embodiment 22 | Extract 80 in the Ramulus Mori | Big legumin 20 | ||
| Embodiment 23 | Extract 5 in the Ramulus Mori | Ginkgetin 95 | ||
| Embodiment 24 | | Big legumin 20 | Ginkgetin 70 | |
| Embodiment 25 | Extract 50 in the Folium Mori | Baicalin 50 | ||
| Embodiment 26 | Extract 20 in the Cortex Mori | Fly water silibin 80 |
Embodiment 27
The method of the total alkaloids that extracts from Ramulus Mori: Ramulus Mori 1000g adds volumn concentration and is 50% ethanol 5L, 70 ℃ of insulations 3 hours, filter, filtering residue adds 50% ethanol 5L again, boils the back soaked overnight, filters, merge filtrate twice, the 1-2 that is concentrated into original volume doubly, and is centrifugal, leaves standstill, add the ethanol precipitation of spending the night, sucking filtration, filtrate are crossed 001 * 7 type cation exchange resin, 0.5N ammonia spirit eluting, collection of biological alkali detects positive part, decolour through activated carbon adsorption again, concentrating under reduced pressure, centrifugal, lyophilization gets 8.06g Ramulus Mori total alkaloids.
Alkaloidal acid-base titrations: getting above-mentioned dry powder 0.5 gram, be dissolved in the 20ml glacial acetic acid, is volumetric solution with 0.1N perchloric acid, records wherein N atom equivalents.Getting above-mentioned dry powder 0.5 gram again, be dissolved in the 20ml water, is volumetric solution with 0.1N NaOH, records wherein carboxylate radical equivalents.N atom equivalents deducts the carboxylate radical equivalents and should be alkaloidal molal quantity, and the alkaloid molecular weight is in 180, and the alkaloid weight of calculating should be not less than 30% of gross weight.
Formula: alkaloid=[perchloric acid volume (mL)-NaOH volume (mL)] * 0.036 * 100%
Embodiment 28
The method of extract total alkaloids from Ramulus Mori: step is with embodiment 27, with 0.05N HCl serves as to extract solvent, extracting method can be that merceration extracts or 50～80 ℃ of heating extraction, and the volume that extracts quantity of solvent is to be extracted 5～15 times of decoction pieces weight, repeats to extract 1-4 time; Remove by filter medicinal residues, be neutralized to neutrality with NaOH, filtrate concentrates; Add ethanol precipitation, remove contamination precipitation; Through centrifugal or filtration, remove residue; Cation exchange resin on the supernatant is washed non-adsorbable to the greatest extent impurity with deionized water, is 0.2-1N ammonia eluting with concentration; The eluent concentrating under reduced pressure is removed ammonia; Through the activated carbon adsorption decolouring, collect destaining solution; Concentrate, make the powdered total alkaloids.
With acid is to extract solvent, and its concentration can also be selected 0.01N, 0.1N or 0.02N, and its acid can also be sulphuric acid.
Embodiment 29
The method of extract total alkaloids from Bombyx mori L.: Bombyx mori L. 1000g, add 50% ethanol 8L, 70 ℃ are incubated 3 hours, filter.Filtering residue adds 50% ethanol 8L again, and 70 ℃ are incubated 3 hours, filter, merge filtrate twice, centrifugal, flocculation, standing over night, sucking filtration, filtrate is crossed 001 * 7 type cation exchange resin, wash non-adsorbable to the greatest extent impurity with deionized water, 0.5N ammonia spirit eluting, collection of biological alkali detects positive part, decolour through activated carbon adsorption again, concentrating under reduced pressure, centrifugal, lyophilization gets the 6.89g silkworm excrement total alkaloid.
Embodiment 30
The alpha-glucosidase of Bombyx mori L. alkaloid and flavone extract suppresses experiment
Get the male Wister rat (1) of body weight 120～140g, get small intestinal after the execution, peel off mesentery, physiological buffer (PBS) flushing enteral content with pre-cooling shreds the back as in the homogenizer, adds 30mlPBS and grinds, 4 ℃, 10,000 rev/mins, centrifugal 10 minutes, get supernatant and get rat small intestine alpha-glucosidase crude enzyme liquid.
Get flavone compounds such as the silkworm excrement total alkaloid of DNJ standard substance, the foregoing description 19 preparations and commercially available catechin, Quercetin, tea polyphenols, the configuration solution in different concentration.Respectively get 200 μ l, add the alpha-glucosidase crude enzyme liquid 100 μ l of above-mentioned condition preparation respectively, 10mg/ml maltose solution 100 μ l are mixed, 37 ℃ of incubations 20 minutes, boiling water heating cessation reaction.The cooling back burst size of determination of glucose oxidase glucose.With the sample concentration is abscissa, the absorbance of 490nm is a vertical coordinate, the inhibition curve of glycosidase is drawn in mapping, silkworm excrement total alkaloid with this method preparation, and the alpha-glucoside inhibiting activity that all presents of flavone compounds such as catechin, Quercetin, tea polyphenols, wherein the glycosidase of total alkaloids suppresses effect significantly better than flavone compound.The (see figure 1) abscissa is that concentration (μ g/ml) vertical coordinate is absorbance 490nm.
The determination of glucose (glucose oxidase method): get testing sample 10 μ l and use (glucose oxidase enzyme reagent kit, time spent preparation) in the working solution in 200 μ l glucose assays, 37 ℃ were reacted 15 minutes, measured its absorbance in the 490nm place.(under the effect of glucoseoxidase, glucose at first is oxidized to gluconic acid and H
2O
2, H
2O
2The catalysis peroxidase synthesizes red quinone imines with 4-amino-antipyrine and phenol, and at the 490nm place absorption maximum is arranged.)
Embodiment 31
Mulberry twigs alkaloid and flavone extract alpha-glucosidase suppress the synergism of effect
Get the male Wister rat (1) of body weight 120～140g, get small intestinal after the execution, peel off mesentery, with physiological buffer (PBS) the flushing enteral content of pre-cooling.Shred the back as in the homogenizer, add 30ml PBS and grind, 4 ℃, 10,000 rev/mins, centrifugal 10 minutes, get supernatant and get rat small intestine alpha-glucosidase crude enzyme liquid.
Concentration is the Ramulus Mori total alkaloids extract of getting acarbose standard substance, the foregoing description 18 of 0.1mg/ml, commercially available catechin, Quercetin, tea polyphenols flavone compound respectively, with and composition thereof each 200 μ l of aqueous solution, add above-mentioned alpha-glucosidase crude enzyme liquid 100 μ l respectively, 10mg/ml maltose solution 100 μ l, be mixed, 37 ℃ of incubations 20 minutes, boiling water heating cessation reaction.Ramulus Mori total alkaloids extract, the flavone compound of Dan Pin investigated with the burst size of determination of glucose oxidase glucose in cooling back, with and composition thereof glycosidase suppress effect.As Fig. 2, the result shows that the same flavone compound of Ramulus Mori total alkaloids (comprising catechin, Quercetin, tea polyphenols) combined effect is better than the inhibition effect of its Dan Pin, shows that it has good synergism.
Embodiment 32
The counter-rotating intestinal capsule test of mulberry twigs alkaloid and flavone extract
Get the male Wister rat of body weight 120～140g, put to death, take out small intestinal, peel off mesentery, with the PBS flushing intestinal contents of pre-cooling.Small intestinal is cut into the segment of 3.5～4cm, with the suction pipe small intestinal that reverses.The intestinal capsule one end cotton thread ligation of counter-rotating adds Krebs-Henseleit buffer 200 μ l from the other end, and ligation intestinal capsule.Rapidly the intestinal capsule is put in the 4ml Krebs-Henseleit solution that is added with finite concentration glycosidase inhibitor sample and 1% starch.Behind the vibration 60min, add 10 μ l 1N HCl cessation reactions in 37 ℃ of water-baths.Take out the intestinal capsule from test tube, collect reactant liquor in intestinal CF and the test tube (the outer liquid of the intestinal capsule that promptly reverses) respectively, the centrifugal 10min of 3000rpm gets supernatant, with the burst size of determination of glucose oxidase glucose.With acarbose is over against photograph, and PBS is a blank, investigates it to the starch hydrolysis and to the influence of glucose absorption.
The result as shown in Table 2, Ramulus Mori total alkaloids extract and flavone compound are united the inhibition effect and the total alkaloids of use, and catechin, Quercetin, tea polyphenols are used separately and are compared, its intestinal capsule is outer to amylolytic inhibition effect, and the inhibition to glucose absorption all obviously strengthens in the intestinal capsule, presents good synergism.
The counter-rotating intestinal capsule test of table 2. Chinese medicine extract
| Glycosidase inhibitor | Use concentration mg/ml | The outer liquid counter-rotating of counter-rotating intestinal capsule intestinal CF IC 50(％)?????????????IC 50(％) |
| Blank acarbose TA catechin Quercetin Tea Polyphenols TA+catechin TA+Quercetin TA+Tea Polyphenols | ???0.0 ???0.1 ???0.1 ???1.0 ???1.0 ???1.0 ???0.1+1.0 ???0.1+1.0 ???0.1+1.0 | ????100.0????????????????100.0 ????26.8±9.2 **?????????42.1±20.0 **????21.7±10.9 **????????32.0±14.2 **????64.5±10.3 **????????85.9±20.4 *????46.6±8.6 **?????????84.2±12.1 *????19.2±7.3 **?????????64.1±16.3 **????14.2±10.2 **????????18.8±6.8 **Δ????????4.0±2.7 **ΔΔ???????????????20.8±9.2 **Δ????????9.2±4.8 **Δ?????????????????40.6±10.0 ** |
Compare with the blank group,
*, p＜0.05;
*, p＜0.01; (n=5)
Compare with the total alkaloids group,
Δ, p＜0.05;
The Δ Δ, p＜0.01; (n=5)
Embodiment 33
Bombyx mori L. alkaloid and flavone extract are to the influence of normal mouse post-prandial glycemia
Choose the 18-22g male mice in kunming, it is divided into positive matched group (acarbose group), blank group (normal saline group) and administration group at random by body weight, every group each 7, (24 ± 1 ℃) feed under the constant temperature, raise with standard feed, freely drink water.Water is can't help in the 16h fasting before the test, gets the mixture and the acarbose of certain density silkworm excrement total alkaloid, flavone compound extract, respective concentration respectively, irritates stomach to normal mouse together with the starch (5g/kg) of certain dosage.Respectively after administration 0,30,60, the 120min tail vein blood, and be collected in the centrifuge tube that contains a certain amount of heparin sodium and normal saline, the centrifugal 10min of 3000rpm gets supernatant, with the determination of glucose oxidase plasma glucose levels, investigate alkaloid and flavone extract and composition thereof influence to the normal mouse carbohydrate tolerance.
The result is as shown in table 3, silkworm excrement total alkaloid and flavone extract (catechin, Quercetin) all can reduce the level of postprandial blood sugar of normal mouse, and can delay the time on blood glucose peak, behind the administration 30min, the administration group is compared with matched group, and there were significant differences for blood glucose value (p＜0.01); And Chinese medicine extract mixture group (total alkaloids+catechin group, total alkaloids+Quercetin group, total alkaloids+catechin+Quercetin group) is compared with independent use of total alkaloids group, behind the administration 30min, also there were significant differences for blood glucose value (p＜0.01), proof total alkaloids and Flavonoid substances compatibility have good synergism, can obviously strengthen the inhibition effect of glycosidase.
Table 3 Chinese medicine extract is to the influence of normal mouse blood tolerance
| Administration time | ???min | ????????0??????????????30????????????60???????????120 |
| Dosage | ???mg/kg | |
| Blank | ???0.0 | ????4.52±0.39????10.41±1.17????7.53±1.34????5.12±0.89 |
| Acarbose catechin Quercetin TA TA+catechin TA+Quercetin TA+catechin+Quercetin | ??4.0 ??8.0 ??8.0 ??4.0 ??4.0+8.0 ??4.0+8.0 ??4.0+8.0+ ??8.0 | ???3.99±0.53????7.31±1.38 **???7.48±1.14????5.60±0.95 ???4.49±0.93????7.93±1.43 **???8.34±2.37 *??5.61±0.72 ???4.28±0.62????8.15±1.86 **???8.09±1.63????6.11±1.06 *???4.08±0.25????7.46±1.35 **???6.01±1.90 **?5.01±1.15 ?????????????????6.05±0.87 ???4.54±0.69???? **ΔΔ?????????????????????5.38±1.03 **?5.24±0.64 ???3.81±0.47????6.49±1.18 **Δ????6.58±0.79 *??4.89±0.95 ?????????????????5.66±1.65 ???4.48±0.42???? **ΔΔ?????????????????????5.82±1.59 **?5.73±1.27 |
Compare with the blank group:
*, p＜0.05;
*, p＜0.01; (n=7)
Compare with the total alkaloids group:
Δ, p＜0.05;
The Δ Δ, p＜0.01; (n=7)
Claims (9)
1. pharmaceutical composition with alpha-glucosidase inhibitor activity, by at least a in the total alkaloids that extracts from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, percentage by weight is 5～90%, flavone extract, percentage by weight is 10～95% to form.
2. a kind of pharmaceutical composition according to claim 1 with alpha-glucosidase inhibitor activity, it is characterized in that the described total alkaloids that extracts is prepared by following method from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori: with Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, after crushed, with the acid of water or 0.01～0.1N or methanol or ethanol or aqueous alcohols serves as to extract solvent, carry out merceration extraction or heating extraction or reflux, extract,, the volume that extracts quantity of solvent is to be extracted 5～15 times of decoction pieces weight, repeats to extract 1-4 time; Remove by filter medicinal residues; Filtrate concentrates; Add ethanol precipitation, remove contamination precipitation; Through centrifugal or filtration, remove residue; Cation exchange resin on the supernatant is washed non-adsorbable to the greatest extent impurity with deionized water, is 0.2-1N ammonia eluting with concentration; The eluent concentrating under reduced pressure is removed ammonia; Through the activated carbon adsorption decolouring, collect destaining solution; Concentrate, make the powdered total alkaloids.
3, a kind of pharmaceutical composition according to claim 1 with alpha-glucosidase inhibitor activity, it is characterized in that the described total alkaloids that extracts from Bombyx mori L. or Ramulus Mori or Cortex Mori or Folium Mori, percentage by weight is 30～80%, flavone extract, and percentage by weight is 20～70% to form.
4. a kind of pharmaceutical composition with alpha-glucosidase inhibitor activity according to claim 1 is characterized in that described flavone extract is a kind of of catechin, Quercetin, tea polyphenols.
5. a kind of pharmaceutical composition according to claim 1 with alpha-glucosidase inhibitor activity, it is characterized in that described flavone extract is catechin, Quercetin, tea polyphenols two kinds, described catechin: Quercetin: the weight ratio of tea polyphenols is 0: 1～9: 1～9 or 1～9: 0: 1～9 or 1～9: 1～9: 0.
6. a kind of pharmaceutical composition according to claim 1 with alpha-glucosidase inhibitor activity, it is characterized in that described flavone extract is catechin, Quercetin, tea polyphenols three kinds, described catechin: Quercetin: the weight ratio of tea polyphenols is 1～9: 1～9: 1～9.
7. a kind of pharmaceutical composition according to claim 1 with alpha-glucosidase inhibitor activity, it is characterized in that described flavone extract be quercitrin, globulariacitrin, hesperidin, puerarin, big legumin, ginkgetin, baicalin, fly in the water silibin at least a.
8. a kind of pharmaceutical composition according to claim 2 with alpha-glucosidase inhibitor activity, it is characterized in that described cation exchange resin is the strong acid type resin of crosslinked polystyrene system, its model is 001 * 1.1 or 001 * 4 or 001 * 7 or 001 * 14.5 or Amberlite IR120 or Dowex 50 or Zerolit 225, and described eluent ammonia concn is 0.5N.
9. any one a kind of pharmaceutical composition with alpha-glucosidase inhibitor activity is treated diabetes, treatment hyperlipidemia, the application in antioxidation, the antidotal medicine in preparation in the claim 1～7.
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