CN104861006B - A kind of furoate glycosides analog 1 and its purposes as α glycosidase inhibitors - Google Patents
A kind of furoate glycosides analog 1 and its purposes as α glycosidase inhibitors Download PDFInfo
- Publication number
- CN104861006B CN104861006B CN201510216225.5A CN201510216225A CN104861006B CN 104861006 B CN104861006 B CN 104861006B CN 201510216225 A CN201510216225 A CN 201510216225A CN 104861006 B CN104861006 B CN 104861006B
- Authority
- CN
- China
- Prior art keywords
- furoate
- parts
- glycosides
- analog
- water
- 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.)
- Expired - Fee Related
Links
Abstract
The present invention relates to the field of Chinese medicines, the preparation α glucosidase inhibitor purposes of more particularly to a kind of furoate glycosides analog 1.The structure of the furoate glycosides analog 1 is the D glucopyranoses of the α of 3 (the first carbonyl of furans 2) epoxide glucopyranosiduronic acid 1 → α of 4 D glucopyranoses 1 → 4, it has stronger rejection ability to α glucuroides, can be further developed as the medicine for treatment and auxiliary treatment diabetes B.
Description
Technical field
The present invention relates to the field of Chinese medicines, more particularly to alpha-glucosidase restrainer.
Background technology
Diabetes (diabetes mellitus) are that a kind of internal insulin is relative or definitely not enough or target cell is to pancreas
There is carbohydrate caused by defect in structure, fat and protein generation in itself in island element sensitiveness reduction, or insulin
Thank to a kind of chronic disease of disorder.It is mainly characterized by hyperglycaemia, glycosuria.Clinical signs are many drinks, more food, diuresis and body weight
Reduce (i.e. " three-many-one-little "), some can be made to organize or organ generation morphosis change and dysfunction, in concurrent ketosis acid
Poison, extremity gangrene, polyneuritis, blindness and renal failure etc..This sick incidence of disease increasingly increases, it has also become global
Common disease, frequently-occurring disease.
Asia diabetology can be revealed, and the total number of persons by national trouble diabetes in 2012 has reached 92,400,000.China
Diabetes present situation is very severe.China is world population big country, because population proportion is big, while Chinese are also for glycosuria
The good hair crowd of disease, and research shows that rich countries Chinese illness rate is more more than 10%.And diabetes mellitus in China over nearly 20 years
Morbidity rises rapidly, and people have to draw attention.
Diabetes (Diabetes) divide the glycosuria of type 1 diabetes, diabetes B, gestational diabetes mellitus and other specific types
Disease.In diabetic, the ratio shared by diabetes B is about 95%.
Diabetes B Etiological is insulin resistance（It is mainly shown as hyperinsulinemia, glucose utilization rate drop
It is low）Exist with the merging of hypoinsulinism, its show be it is inhomogenous, have based on insulin resistance with insulin
Hyposecretion, what is had is then with or without insulin resistance with hypoinsulinism.Its primary treatment regimen is oral
Non-insulin class medicine, based on Western medicine, its side effect is obvious, such as hypoglycemia, strong feeling of empty stomache, cold sweat, general weakness；
And be generally external pharmaceuticals's production, price is high, sufferer heavy load.
Oral non-insulin hypoglycemic medicine mainly includes：Biguanides, sulfonylurea drugs, Thiazolidinediones,
Glinides, alpha-glucosidase inhibitor, dipeptidyl peptidase-4（DPP-4）Inhibitor etc..Based on chemicals.
The persevering Ji of relatively common blood-sugar lowering tcm drug pleases safe capsule, diabetes pill etc. now.Country's medicinal industry is badly in need of curative effect at present
Definitely, the Traditional Chinese medicine historical preparation of Small side effects.
Alpha-glucosidase is located on intestinal villus film, can by carbohydrate degradation, so that postprandial blood sugar is raised, and α-
Glucosidase inhibitor can competitively slow down the degraded of carbohydrate and be absorbed.Alpha-glucosidase is had at present
Inhibitor such as acarbose and Fu Gelie polysaccharide are applied to the clinical treatment of diabetes as OHA, and it can be effective
Level of postprandial blood sugar is controlled, but this kind of alpha-glucosidase restrainer is simply a small number of after all at commercially available aspect, and also it mostly contains
Have glycosyl, synthesis step is also and its cumbersome, in addition, in clinicing aspect its have certain side effect can such as cause flatulence and
Diarrhoea etc..Therefore, increasing scholar starts to favor in the artificial conjunction of searching natural products replacement from food or medicinal plant
Into alpha-glucosidase restrainer, to ensure its security row and validity.
Project team is during the prescription of blood-sugar lowering tcm drug compound, chemical composition, pharmacology activity research, an isolated tool
There is the furoate glycosides analog I of alpha-glucosaccharase enzyme inhibition, by data analyses such as mass spectrum, nuclear magnetic resonance, identify that it is tied
Structure --- 3- (furans -2- first carbonyl) -1 α of epoxide glucopyranosiduronic acid → -1 α of 4-D- glucopyranoses → 4-D- glucopyras
Sugar, its structure is as follows.
The content of the invention
Based on above Research foundation, an object of the present invention is to provide furoate glycosides analog I preparation technology.
To achieve these goals, the technical scheme is that：
（1）Take 5 parts of red ginseng, 8 parts of Poria cocos, 8 parts of the bighead atractylodes rhizome, 6 parts of the Radix Astragali, 6 parts of the root of kudzu vine, 10 parts of sealwort, 2 parts of rheum officinale, the coptis 2
Part, 4 parts of the fruit of Chinese wolfberry, 2 parts of the fruit of Chinese magnoliavine, 1 part of radix glycyrrhizae, crush, and mix, plus 10 times of amounts（w/w）Decocting is boiled 2 times, 1 hour every time, filter
Cross, merging filtrate；
（2）Step（1）Middle filtrate is concentrated into relative density 1.15 ~ 1.30（30 degrees Celsius of surveys）, 95% ethanol is added, makes second
Determining alcohol reaches 50% ~ 75%, and filtrate is collected in static 12 hours to 24 hours of room temperature, filtering, and filtrate is evaporated, is suspended with water；
（3）Step（2）Middle aqueous suspension is extracted 3 times with isometric ethyl acetate, discards ethyl acetate layer, water layer again with etc.
Volume water saturation extracting n-butyl alcohol, merges butanol extraction liquid, is evaporated n-butanol, and residue adds water redissolution, obtains Aqueous extracts；
（4）Step（3）Middle Aqueous extracts are separated with hydroxypropyl sephadex chromatography, methanol water elution, are collected and are rich in furancarboxylic acid
Ester glycosides analog I eluent, is concentrated, crystallization；
（5）Step（4）In crystallization dissolved with methanol-water, recrystallize, filtering, obtain furoate glycosides analog I.
The second object of the present invention is to provide a kind of furoate glycosides analog I application, and the application is treatment diabetes B
A kind of new medicine is provided.
To achieve these goals, the technical scheme is that：
Furoate glycosides analog I is used for the application for preparing the medicine for the treatment of diabetes B.
Described furoate glycosides analog I is used for the medicine for preparing alpha-glucosidase Inhibitors for Type 2 Diabetes Mellitus
Using can be prepared by following methods：
Take furoate glycosides analog I, tablet is made, capsule, powder, pill, soft in additional pharmacy acceptable auxiliary material
The pharmaceutically acceptable formulation such as capsule.
Embodiment
For the more detailed description present invention, following preparating examples are provided.But the scope of the present invention is not limited thereto.
Embodiment 1：Alpha-glucosidase restrainer furoate glycosides analog I preparation
1. furoate glycosides analog I preparation
（1）Take red ginseng 500g, Poria cocos 800g, bighead atractylodes rhizome 800g, Radix Astragali 600g, root of kudzu vine 600g, sealwort 1000g, rheum officinale 200g,
Coptis 200g, fruit of Chinese wolfberry 400g, fruit of Chinese magnoliavine 200g, radix glycyrrhizae 100g, are crushed, and are mixed, plus 50 L decoctings boil 2 times, 1 hour every time,
Filtration, merging filtrate；
（2）Step（1）Middle filtrate is concentrated into relative density 1.25, adds 95% ethanol, concentration of alcohol is reached 60%, room temperature
Static 18 hours, filtrate was collected in filtering, and filtrate is evaporated, is suspended with water；
（3）Step（2）Middle aqueous suspension is extracted 3 times with isometric ethyl acetate, discards ethyl acetate layer, water layer again with etc.
Volume water saturation extracting n-butyl alcohol, merges butanol extraction liquid, is evaporated n-butanol, and residue adds water redissolution, obtains Aqueous extracts；
（4）Step（3）Middle Aqueous extracts are separated with hydroxypropyl sephadex chromatography, methanol water elution, are collected and are rich in furancarboxylic acid
Ester glycosides analog I eluent, is concentrated, crystallization；
（5）Step（4）In crystallization dissolved with methanol-water, recrystallize, filtering, obtain furoate glycosides analog I.
2. furoate glycosides analog I structural research
Furoate glycosides analog I, white crystals（Methanol-water）, Molish, which reacts, to be positive, and illustrates to contain in the compound
Sugar.ESI-MS m/z：611.3[M-H]+, infer that molecular formula is C with reference to H NMR spectroscopy23H32O19, molecular weight is 612.Through hydrolysis, PMP
Derivatization HPLC-UV is detected, as a result shows to contain 2 molecule D-Glucoses and 1 molecule D-Glucose aldehydic acid in the molecule.
1HNMR (300MHz, MeOD+D2O in) composingδppm：Provide 3 groups of proton signals in low field, 7.50 (dd, 1H, J=
0.9,1.8Hz, H-5 ' ' ' ') it is furans -2- formic acid 5 alkene hydrogen signals of group, 7.11 (dd, 1H, J=0.9,3.6Hz, H-
3 ' ' it is ' ') furans -2- formic acid 3 alkene hydrogen signals of group, 6.44 (dd, 1H, J=1.8,3.6Hz, H-4 ' ' ' ') for furans-
4 alkene hydrogen signals of 2- formic acid group, together constitute furans -2- formic acid groups；During midfield provides 3 glycan molecules 3.5 ~ 5.5
Connect hydrogen signal on hydroxyl carbon, wherein 5.32 (d, 1H, J = 3.4Hz, H-1’’)、5.12(d, 1H, J = 3.6Hz, H-
1’)、5.06(d, 1H, J=3.2Hz, H-1) it is respectively two D-Glucoses and a hydrocarbon letter of D-Glucose aldehydic acid end group
Number, coupling constant shows that 3 sugar are α-sugar.
13CNMR (75MHz, MeOD+D2O in) composingδppm：Low field provides 9 signals, including 168.5（C6）、162.3
（C1’’’）、145.1（C5’’’’）、144.1（C2’’’’）、116.7（C3’’’’）、110.7（C4’’’’）、107.5（C1）、
107.5（C1’）、98.6（C1’’）；Wherein 162.3（C1’’’）、145.1（C5’’’’）、144.1（C2’’’’）、116.7
（C3’’’’）Common furans -2- formic acid groups；168.5（C6）For alpha-D-glucose aldehydic acid carboxyl carbon signal, 107.5（C1）、
107.5（C1’）、98.6（C1’’）For three sugared terminal carbon signals, wherein 107.5（C1）、107.5（C1’）For into glycosidic bond terminal
Carbon signal.Midfield 83.1（C4’）、82.9（C4’’）、80.6（C5）、79.4（C5’）、79.2（C5’’）、74.2（C2’）、74.0
（C3’）、73.7（C3’’）、72.3（C2’’）、70.8（C3）、70.1（C2）、68.6（C4）、62.6（C6’）、62.4（C6’’）Give
3 sugared other carbon signals are gone out.
The ownership of each carbon, hydrogen signal is further demonstrated by HMQC.By HMBC spectrums determine furans -2- formic acid and α -
After C3 hydroxyls dehydrates of D-Glucose aldehydic acid be connected, alpha-D-glucose aldehydic acid is connected with alpha-D-glucose 1-4, alpha-D-glucose and
Another alpha-D-glucose 1-4 is connected.Correlation information is as follows.
In summary, the structure for determining furoate glycosides analog I is 3- (furans -2- first carbonyl) epoxide glucopyra alditol
- 1 α of acid → -1 α of 4-D- glucopyranoses → 4-D- glucopyranoses.
2. furoate glycosides analog I alpha-glucosaccharase enzyme inhibition activity research
2.1 materials and method
2.1.1 experiment material
Sample：Furoate glycosides analog I.
Reagent：Acarbose；Alpha-glucosidase（≧5000u/g）；The reagents such as disodium hydrogen phosphate, potassium dihydrogen phosphate are
Analysis is pure.
Instrument：Electronic balance, vortex mixed instrument, numerical control ultrasonic cleaner, automatic ELIASA.
2.1.2 experimental method
2.1.2.1 the preparation of need testing solution
The mg of furoate glycosides analog I 5 are taken, it is accurately weighed, it is dissolved in water, is configured to concentration for 20 mgmL-1It is molten
Liquid, it is standby.
2.1.2.2 alpha-glucosaccharase enzyme inhibition activity is determined
Sucrose is decomposed into glucose in the presence of alpha-glucosidase, passes through determination of glucose oxidase reaction system
The growing amount of middle glucose, calculates inhibitory action of the test sample to alpha-glucosidase activity.Need testing solution is taken, is diluted to and is
Row concentration.During experiment, the μ L of need testing solution 10 of series concentration are taken respectively, add 0.5 umL-1Alpha-glucosaccharase enzyme solutions
10 μ L, add 25 mmolL-1The μ L of sucrose 10, are incubated 15 minutes, this reacts on complete on 96 well culture plates at 37 DEG C
Into using glucose oxidase method, with ELIASA, absorbance is determined under 490 nm wavelength（A）, with the generation of glucose
Amount calculates inhibiting rate as index；Acarbose is chosen as positive control drug, blank control, negative control and sample is concurrently set
Product are compareed.Inhibition of enzyme activity rate（%）It is calculated as follows：
Inhibition of enzyme activity rate %=[A It is negative- (A Sample - A Sample controls)] / (A It is negative- A Blank)×100%
In formula：A It is negativeTo be added without the absorbance of sample solution reaction system；A SampleTo add sample solution reaction system
Absorbance；A Sample controlsTo add sample solution but being added without the absorbance of alpha-glucosidase reaction system；A BlankFor cushioning liquid
Absorbance.
The alpha-glucosaccharase enzyme inhibition activity IC of sample50Represent, IC50To be reached to alpha-glucosaccharase enzyme inhibition rate
The concentration of need testing solution when 50%.
2.1.2.3 data statistic analysis
IC is calculated with ORIGIN softwares50Value, IC50Value is smaller, represents that its rejection ability to alpha-glucosidase is got over
By force.
2.2 results and analysis
Tested more than, the IC of the furoate glycosides analog I of measure to alpha-glucosaccharase enzyme inhibition rate50For 0.51
mg·mL-1, and IC of the acarbose to alpha-glucosaccharase enzyme inhibition rate under the same terms50Only 1.07 mgmL-1, furoate
Glycosides analog I is acarbose to the rejection ability of alpha-glucosidase more than 2 times.
2.3 conclusion
Furoate glycosides analog I has stronger rejection ability to alpha-glucosidase, using furoate glycosides analog I as original
Material can further develop the medicine for treating diabetes B, and its rejection ability to alpha-glucosidase has exceeded A Kabo
Sugar.
Embodiment 2：The preparation of furoate glycosides analog I soft capsules
Furoate glycosides analog I is taken, is suspended using soybean oil, beeswax as solvent, soft capsule is made.
Embodiment 3：The preparation of furoate glycosides analog I tablets
Furoate glycosides analog I, plus dextrin granulation are taken, is dried, tablet is made in whole grain, tabletting.
Claims (3)
1. it is a kind of such as the furoate glycosides analog 1 of following formula：
Its chemical name is 3- (furans -2- first carbonyl) -1 α of epoxide glucopyranosiduronic acid → -1 α of 4-D- glucopyranoses → 4-
D- glucopyranoses.
2. a kind of preparation method of furoate glycosides analog 1 as claimed in claim 1, it is characterised in that comprise the following steps：
（1）Take 5 parts of red ginseng, 8 parts of Poria cocos, 8 parts of the bighead atractylodes rhizome, 6 parts of the Radix Astragali, 6 parts of the root of kudzu vine, 10 parts of sealwort, 2 parts of rheum officinale, 2 parts of the coptis, Chinese holly
4 parts of matrimony vine, 2 parts of the fruit of Chinese magnoliavine, 1 part of radix glycyrrhizae, crush, and mix, plus 10 times of amounts（w/w）Decocting is boiled 2 times, 1 hour every time, is filtered, is closed
And filtrate；
（2）Step（1）Middle filtrate is concentrated into relative density 1.15 ~ 1.30, adds 95% ethanol, make concentration of alcohol reach 50% ~
75%, filtrate is collected in static 12 hours to 24 hours of room temperature, filtering, and filtrate is evaporated, is suspended with water；
（3）Step（2）Middle aqueous suspension is extracted 3 times with isometric ethyl acetate, discards ethyl acetate layer, water layer is again with isometric
Water-saturated n-butanol is extracted, and is merged butanol extraction liquid, is evaporated n-butanol, and residue adds water redissolution, obtains Aqueous extracts；
（4）Step（3）Middle Aqueous extracts are separated with hydroxypropyl sephadex chromatography, methanol water elution, are collected and are rich in furoate glycosides
The eluent of analog 1, is concentrated, crystallization；
（5）Step（4）In crystallization dissolved with methanol-water, recrystallize, filtering, obtain furoate glycosides analog 1；
Step（2）The measurement temperature of middle relative density is 30 DEG C.
3. application of the furoate glycosides analog 1 as claimed in claim 1 in alpha-glucosidase restrainer is prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510216225.5A CN104861006B (en) | 2015-05-03 | 2015-05-03 | A kind of furoate glycosides analog 1 and its purposes as α glycosidase inhibitors |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510216225.5A CN104861006B (en) | 2015-05-03 | 2015-05-03 | A kind of furoate glycosides analog 1 and its purposes as α glycosidase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104861006A CN104861006A (en) | 2015-08-26 |
| CN104861006B true CN104861006B (en) | 2017-10-27 |
Family
ID=53907233
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510216225.5A Expired - Fee Related CN104861006B (en) | 2015-05-03 | 2015-05-03 | A kind of furoate glycosides analog 1 and its purposes as α glycosidase inhibitors |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104861006B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1235551A (en) * | 1996-11-01 | 1999-11-17 | 参天堂制药株式会社 | Pharmaceutical composition for diabetes |
| CN101138369A (en) * | 2006-09-06 | 2008-03-12 | 蔡如桂 | Thirst-eliminating tea |
-
2015
- 2015-05-03 CN CN201510216225.5A patent/CN104861006B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1235551A (en) * | 1996-11-01 | 1999-11-17 | 参天堂制药株式会社 | Pharmaceutical composition for diabetes |
| CN101138369A (en) * | 2006-09-06 | 2008-03-12 | 蔡如桂 | Thirst-eliminating tea |
Non-Patent Citations (1)
| Title |
|---|
| 黄连多糖的提取方法、单糖组成及其抑制α-葡萄糖苷酶活性研究;唐策;《成都中医药大学2013届硕士研究生学位论文》;20140615;全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104861006A (en) | 2015-08-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102370671B (en) | Active fraction in lucid ganoderma fruiting body, extracting method, application thereof and preparation | |
| CN101229316B (en) | Rhizoma anemarrhenae extrac | |
| CN108186731A (en) | A kind of method extracted with natural alpha-glucosidase restrainer in quick screening Radix Astragali | |
| CN111349017B (en) | Process for extracting compound from dendrobium nobile lindl and application thereof | |
| CN104069348A (en) | Sealwort extract as well as preparation method and use thereof | |
| CN102872064A (en) | Method for extracting alpha-glucosidase activity inhibitor from lycium barbarum seeds and residues after extraction of lycium barbarum oil from lycium barbarum seeds and application thereof | |
| CN102349945B (en) | Method for extracting purified total flavonoids from lindera reflexa hemsl by means of macroporous absorption resin | |
| CN102423343A (en) | Broussonetia papyrifera total flavonoids extract, its preparation method and its application | |
| CN101307090B (en) | Method for preparing timosaponin BIII and uses thereof | |
| CN101919901B (en) | Application of total aglycone of Gleditsia sinensis Lam in preparation of alpha-glucosidase inhibitor drugs | |
| CN105125941A (en) | Preparation method of assistant hypoglycemic corn-stigma extractive capsules | |
| CN101224240A (en) | Antidiabetics extract, preparing method and uses thereof | |
| CN104861006B (en) | A kind of furoate glycosides analog 1 and its purposes as α glycosidase inhibitors | |
| CN101167781A (en) | Orally-administered hypoglycemic sweet potato leaf single prescription traditional Chinese medicine and preparation method thereof | |
| CN107674108B (en) | Application of stigmastane steroid compound in preparing medicine for treating diabetes or obesity | |
| CN107266464B (en) | A kind of rhizoma alismatis decoction extract and its application | |
| CN108310226A (en) | It is a kind of to have effects that prevent the composition and the preparation method and application thereof of diabetes | |
| CN107446009A (en) | The O β D glucuronic acid methyl esters of chrysoeriol 7 and its extracting method and purposes | |
| CN107383122A (en) | The method that α glucosidase inhibitors are extracted from carambola root | |
| CN107501367A (en) | The O β D glucuronic acids butyl esters of chrysoeriol 7 and its extracting method and purposes | |
| Lolok et al. | Stigmasterol isolated from the ethyl acetate fraction of Morinda citrifolia fruit (using the bioactivity‑guided method) inhibits α‑amylase activity: In vitro and in vivo analyses | |
| CN110483657A (en) | A kind of lobelia chinensis homogeneous polysaccharide and its preparation method and application | |
| CN105232676B (en) | A kind of Chinese medicine for treating diabetes and preparation method thereof | |
| CN106265699B (en) | Three galla turcica acidic group of the β -1,6- hexahydroxy biphenyl diformyl -2,3,4--application of D-Glucose compound in medicine preparation | |
| CN104000896A (en) | Malus toringoides extractive and manufacturing method and purpose thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20171027 Termination date: 20180503 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |