CN101972245B - Composition capable of promoting insulin secretion and inhibiting generation of advanced glycosylation end products - Google Patents
Composition capable of promoting insulin secretion and inhibiting generation of advanced glycosylation end products Download PDFInfo
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Abstract
The invention relates to a composition capable of promoting insulin secretion and inhibiting generation of advanced glycosylation end products. The composition comprises the following components in percentage by mass: 5-95% of proanthocyanidin extract and 5-95% of dihydrochalcone. The main component of the proanthocyanidin extract is proanthocyanidin which accounts for 50-70% of the mass of the extract. The composition lays a foundation for the production of the future compound medicines, is beneficial to controlling blood sugar of diabetics and preventing and treating diabetic complications. The composition of the invention has the advantage that the multifunctional synergistic effect is obviously superior to effect of each independently used component.
Description
Technical field
The present invention relates to a kind of compositions that promotes insulin secretion and suppress the advanced glycosylation end product nucleus formation that has.
Background technology
Diabetes be since in the body hormone of insulin deficit or antagonism insulin increase, or insulin can not be brought into normal play physiological action and a kind of syndrome of the glucose, protein and the lipid metabolic disorder that cause in target cell.Diabetes and complication thereof such as cataract, nephropathy and cardiovascular disease are having a strong impact on human health.Traditional OHA curative effect is limited and single; Diabetes and the composition of medicine of complication thereof of developing the multiaction target spot of new natural origin have become focus; The present invention is directed to this demand, developed not only to have the insulin secretagogue effect but also have advanced glycosylation end product and generate the inhibiting preparation of compositions method that comes from Cortex Cinnamomi, gold buckwheat raw anthocyanin extract and come from the Sanguis Draxonis dihydrochalcone.
In recent years big quantity research shows, lasting hyperglycemia causes multiple proteins nonenzymatic glycosylation in the body and the terminal glycosylation dead end product AGEs (Advanced Glycation Endproducts) that forms thus plays an important role in the pathogenesis of chronic complicating diseases of diabetes such as diabetic nephropathy, diabetic ophthalmopathy, diabetic cardiovascular disease.The generation that suppresses AGEs is to slow down with such disease of control one of effective means with development takes place, so the research and development of AGEs inhibitor have caused that people pay close attention to greatly.At present the most promising medicine be aminoguanidine (Aminoguanidine, AG).Aminoguanidine is a kind of nucleophilic hydrazine class compound, its main and glycosylation intermediate product 3-deoxyfructose (3-deoxyglucosone) reaction, thereby the formation of inhibition AGEs.But pharmacological evaluation confirms the blood that aminoguanidine can reduce islets of langerhans and supplies, and can suppress the B cells of pancreas excreting insulin during high concentration, thereby limit it in clinical practice, in the experiment of AGEs inhibitor screening only with aminoguanidine as the positive control medicine.Therefore seek that ideal not only to have had insulin secretagogue but also can suppress single medicine or compositions that nonenzymatic glycosylation generates be an important research direction.
Advanced glycosylation end product AGEs is that one type of irreversible polymer that non-enzymatic reaction forms takes place for reducing sugar and protein.Glycosylation is divided into two stages: early stage at glycosylation, and under the condition of no enzyme, the glucose molecule free aldehyde of open chain or ketone group and gal4 amino acid residue side chain epsilon-amino or aminoterminal alpha-amido pass through the nucleophilic combination; Generating a reversible unsettled intermediate product aldimine (aldimine) rapidly is schiff alkali; Reach balance in vivo very soon, subsequently, molecular structure can slowly take place the schiff base resets; Form sugar-protein ketoamine conjugate more stable but that the reaction reversibility lowers greatly; Through arranging again, can form the more stable 1-amino of character-1-deoxidation-d-ketose, i.e. amadori product; In the late period of glycosylation, the amadori product further with other free amine groups reactions, forms irreversible glycosylation end product AGEs at last through the reactive carbonyl compound of multiple height of multistep dehydration and molecular rearrangement generation.The physics and chemistry biochemistryization characteristic of AGEs is: be sepia; There is popularity, has fluorescence, the heterogeneity of bridging property and irreversibility, structure, enzyme is stablized, is difficult for being degraded, but can combine the unwholesome biological effect of performance with many cell membrane specific receptors.
Summary of the invention
One of the object of the invention is to provide a kind of compositions that promotes insulin secretion and suppress the advanced glycosylation end product nucleus formation that has.
Two of the object of the invention is to provide the method for preparing of said composition.
Sanguis Draxonis (Dragon ' s Blood) be a kind of natural product, also be one of traditional Chinese medicines kind, Palmae kylin Sanguis Draxonis and Liliaceae dracaena [Dracaena cochinchinensis (Lour.) S.C.Chen] Sanguis Draxonis is arranged.The basic research proof Sanguis Draxonis of animal serum medicine chemistry and pharmacokinetics has significant hypoglycemic activity, and 4 prototype composition dihydrochalcones have significant insulin secretagogue effect in the Sanguis Draxonis.Its precursor structure as lead compound tens of kinds of dihydrochalcone derivants have been synthesized; Filter out stronger the first five of insulin secretion accelerating and plant chemical compound; Wherein chemical compound 4 '-methoxyl group-2 ', 3,4-trihydroxy dihydrochalcone and chemical compound 2; 4-dimethoxy-2 ', 5 '-the dihydroxy dihydrochalcone also have simultaneously the aminoguanidine of being higher than the AGEs inhibitory action.
Cortex Cinnamomi is the cinnamomic dry bark of Lauraceae Cinnamomum aiphyllium, is a kind of medicine food dual purpose plant resource.Current cinnamomic practical application is main with spice and Chinese medicine preparation, does not appear in the newspapers as yet for the research of Cortex Cinnamomi as AGEs formation inhibitor and preparation method thereof.
Wild Rhizoma Fagopyri Dibotryis (Fagopyrum dibotrys) is the buckwheat herbaceos perennial, is a kind of nutritious and have a resource plant of important medical value.Modern study confirms that the effective ingredient that the Rhizoma Fagopyri Dibotryis rhizome mainly contains is the mixture of one type of procyanidin.Gold buckwheat raw anthocyanin does not appear in the newspapers as the research of AGEs formation inhibitor and preparation method thereof as yet.
Discover: in natural product, Sanguis Draxonis, Cortex Cinnamomi and Rhizoma Fagopyri Dibotryis have the insulin secretagogue effect and AGEs generates inhibitory action.And in the various extracts of Cortex Cinnamomi, Rhizoma Fagopyri Dibotryis; The procyanidin of finding Cortex Cinnamomi, Rhizoma Fagopyri Dibotryis through screening has the AGEs inhibitory action more stronger than aminoguanidine; With the dihydrochalcone derivative compound 4 ' methoxyl group-2 that comes from Sanguis Draxonis '; 3,4-trihydroxy dihydrochalcone and chemical compound 2 ,-dimethoxy-2 '; 5 '-two kinds of chemical compounds of dihydroxy dihydrochalcone and Cortex Cinnamomi and two kinds of extracts of Rhizoma Fagopyri Dibotryis make up by a certain percentage and match, promptly obtain a series of not only had the insulin secretagogue effect but also had advanced glycosylation end product AGEs generate inhibiting compositions.
According to above-mentioned theory, the present invention adopts following technical scheme:
A kind of compositions that has the promotion insulin secretion and suppress the advanced glycosylation end product nucleus formation is characterized in that the composition of said composition and quality percentage composition are:
Procyanidin extract 5～95%,
Dihydrochalcone 5～95%;
The main component of described procyanidin extract is a procyanidin, and its quality percentage composition is 50%～70% of an extract.
Above-mentioned procyanidin extract extracts from Cortex Cinnamomi or Rhizoma Fagopyri Dibotryis.
The concrete grammar of the above-mentioned procyanidin that from Cortex Cinnamomi, extracts is: after Chinese medicine cinnamon is pulverized, cross 40～60 mesh sieves, obtain Cortex Cinnamomi coarse powder material; This Cortex Cinnamomi coarse powder material with petroleum ether Suo Shi extracting, is volatilized solvent; To press Cortex Cinnamomi powder through the Cortex Cinnamomi powder after the Suo Shi extracting: distilled water=1: 10～3: 10 mass ratio mixes, 50～60 ℃ of stirring and leaching 30～120 minutes; Filter cleaner adds 2～5 times of volume ethanol again, and ice-water bath stirred 30～120 minutes; Filter and remove deposition, reclaim ethanol, get extracting solution; This extracting solution is carried out column chromatography for separation purify, concentrating under reduced pressure, vacuum drying gets procyanidin extract, and wherein the quality percentage composition of procyanidin is 65～75%.
Above-mentioned column chromatography for separation method of purification is: adopt macroporous resin column chromatography, earlier with 3～5 times of column volume distilled water flushings, use 30～90% ethanol elutions then, collect eluent.
Above-mentioned macroporous resin column is: HP20, D101, LSA21 or ADS17.
The method for preparing of the procyanidin that from Rhizoma Fagopyri Dibotryis, extracts; See also Chinese patent " extraction of golden buckwheat high polymeric procyanidin and catalytic degradation thereof prepare the method for Oligomeric Proanthocyanidins "; Its number of patent application: the method in 20090050368.8 is carried out, as follows with the method narration at present:
A) Rhizoma Fagopyri Dibotryis being crushed to particle diameter is 1～3cm, obtains the Rhizoma Fagopyri Dibotryis bullion;
B) above-mentioned Rhizoma Fagopyri Dibotryis bullion use concentration of volume percent is 40%～90% ethanol water lixiviate, and temperature is 50～70 ℃, and the time is 1～2 day, gets lixiviating solution;
C) above-mentioned lixiviating solution is flung to ethanol, add water to and wave pure half preceding volume, stir the centrifugal 10～20min in back, rotating speed is 3000～5000rpm, abandons deposition, and supernatant with the extraction of organic solvent ethyl acetate equal-volume, is got the water raffinate;
D) with LSA-21 macroporous resin column on the water raffinate, at first use 2～5 times of column volume distilled water washs, the concentration of volume percent of 2～4 column volumes of reuse is 30%～70% ethanol water eluting, collects eluent;
E) with obtaining the golden buckwheat high polymeric procyanidin extract after the eluent concentrating under reduced pressure of collecting, the drying.Wherein the quality percentage composition of procyanidin is 55～70%;
4 '-methoxyl group-2 ', 3,4-trihydroxy dihydrochalcone and 2; 4-dimethoxy-2 ', 5 '-synthesis technique of dihydroxy dihydrochalcone, please refer to Chinese patent " 4 '-hydroxyl-2; The method for preparing of 4-methylenedioxy dihydrocharcone ", (patent No.: ZL200810034743.5).
The existing oral antidiabetic drug generally has only single target spot pharmacological action at present; The gliclazide of insulin secretagogue effect for example; Suppress the acarbose of glycosidase effect, the metformin of insulin-sensitizing effect and aminoguanidine of inhibition advanced glycosylation end product nucleus formation etc.; Curative effect is single, and shortage can blood sugar lowering can be treated the composition of medicine of the multiaction target spot of diabetic complication again.The present invention is directed to this demand, developed and not only have promoting insulin secretion but also have the preparation of compositions method that suppresses the advanced glycosylation end product nucleus formation.The procyanidin that comes from Cortex Cinnamomi and Rhizoma Fagopyri Dibotryis has the AGEs inhibitory action more stronger than aminoguanidine; Come from chemical compound 4 in the dihydrochalcone derivant of Sanguis Draxonis '-methoxyl group-2 '; 3,4-trihydroxy dihydrochalcone and 2,4-dimethoxy-2 '; 5 '-the dihydroxy dihydrochalcone except having the insulin secretagogue effect that is better than gliclazide, also have the AGEs inhibitory action.Compositions can be from now on that the birth of compound medicine lays the foundation, and the glycemic control that will help diabetics helps the prevention and the treatment of diabetic complication again.The advantage of compositions of the present invention is multi-functional cooperative effect, obviously is superior to each component and uses separately.
The specific embodiment:
Embodiment 1～10: the ratio of various components is listed in table 1 in the compositions
The ratio of various components in table 1 compositions
Embodiment 16: the extraction process process and the step of Cortex Cinnamomi procyanidin is following in the present embodiment:
(1) Chinese medicine cinnamon is carried out mechanical activation comminution, granule is crossed 50 mesh sieves, obtains Cortex Cinnamomi coarse powder material;
(2) get the above-mentioned Cortex Cinnamomi coarse powder of 5g material and carry out the Suo Shi extracting with petroleum ether, 70 ℃ were extracted after 10 hours, took out Cortex Cinnamomi powder, volatilized petroleum ether;
(3) above-mentioned Suo Shi is extracted the back Cortex Cinnamomi powder, add the 50mL distilled water, heated and stirred lixiviate 60 minutes, filter cleaner gets lixiviating solution; In this lixiviating solution, add 200mL ethanol, put ice-water bath stirring 30min, filter then and remove white precipitate, ethanol is reclaimed in the filtrate decompression distillation, gets aqueous extract;
(4), cross the ADS17 post with above-mentioned aqueous extract; Earlier use the 200mL distilled water flushing, and then use 70% alcohol flushing, collect eluent, concentrating under reduced pressure reclaims ethanol, promptly gets Chinese medicine cinnamon extract 75mg behind the vacuum drying, and yield is 1.5%.
Embodiment 17: the extraction process process and the step of Cortex Cinnamomi procyanidin is following in the present embodiment:
(1) Chinese medicine cinnamon is carried out mechanical activation comminution, granule is crossed 60 mesh sieves, obtains Cortex Cinnamomi coarse powder material;
(2) get the above-mentioned Cortex Cinnamomi coarse powder of 5g material and carry out the Suo Shi extracting with petroleum ether, 70 ℃ were extracted after 10 hours, took out Cortex Cinnamomi powder, volatilized petroleum ether;
(3) above-mentioned Suo Shi is extracted the back Cortex Cinnamomi powder, add the 75mL distilled water, heated and stirred lixiviate 60 minutes, filter cleaner gets lixiviating solution; In this lixiviating solution, add 200mL ethanol, put ice-water bath stirring 60min, filter then and remove white precipitate, ethanol is reclaimed in the filtrate decompression distillation, gets aqueous extract;
(4), cross the HP20 post with above-mentioned aqueous extract; Earlier use the 200mL distilled water flushing, and then use the 50mL70% alcohol flushing, collect eluent, concentrating under reduced pressure promptly gets Chinese medicine cinnamon extract 90mg behind the vacuum drying, and yield is 1.8%.
Embodiment 18: the extraction process process and the step of Cortex Cinnamomi procyanidin is following in the present embodiment:
(1) the Chinese medicine cinnamon wheat is carried out mechanical activation comminution, granule is crossed 40 mesh sieves, obtains Cortex Cinnamomi coarse powder material;
(2) get the above-mentioned Cortex Cinnamomi coarse powder of 5g material and carry out the Suo Shi extracting with petroleum ether, 70 ℃ were extracted after 10 hours, took out Cortex Cinnamomi powder, volatilized petroleum ether;
(3) above-mentioned Suo Shi is extracted the back Cortex Cinnamomi powder, add the 75mL distilled water, heated and stirred lixiviate 90 minutes, filter cleaner gets lixiviating solution; In this lixiviating solution, add 200mL ethanol, put ice-water bath stirring 60min, filter then and remove white precipitate, ethanol is reclaimed in the filtrate decompression distillation, gets aqueous extract;
(4), cross the LSA21 post with above-mentioned aqueous extract; Earlier use the 200mL distilled water flushing, and then use the 50mL70% alcohol flushing, collect eluent, concentrating under reduced pressure promptly gets Chinese medicine cinnamon extract 105mg behind the vacuum drying, and yield is 2.1%.
The resulting Cortex Cinnamomi extract outward appearance of the inventive method is a light coffee color, good water solubility, and mouthfeel is light, does not have bad sensation.
Embodiment 19: the extraction process process and the step of gold buckwheat raw anthocyanin is following in the present embodiment:
(1) the Chinese medicine Rhizoma Fagopyri Dibotryis is pulverized, grain diameter obtains the Rhizoma Fagopyri Dibotryis bullion greatly about 1～3cm;
(2) above-mentioned Rhizoma Fagopyri Dibotryis bullion 200g being used 50% alcoholic solution lixiviate, material and solution ratio is that 1: 6, temperature are that 50 ℃, time are 24 hours;
(3) lixiviating solution is flung to ethanol, adds water to 600ml, stirs the centrifugal 10min in back, and rotating speed is 3000rpm, abandons deposition, and supernatant with ethyl acetate equal-volume extracted twice, is collected the water raffinate;
(4) LSA-21 macroporous resin column on the water raffinate is at first used 3 times of column volume distilled water washs, the alcoholic solution eluting of 3 column volumes 50% of reuse.With obtaining golden buckwheat high polymeric procyanidin 10.23g after the eluent concentrating under reduced pressure of collecting, the drying, procyanidin content is 58.45%, and average degree of polymerization is 5.8.
Embodiment 20: the extraction process process and the step of gold buckwheat raw anthocyanin is following in the present embodiment:
(1) the Chinese medicine Rhizoma Fagopyri Dibotryis is pulverized, grain diameter obtains the Rhizoma Fagopyri Dibotryis bullion greatly about 1～3cm;
(2) above-mentioned Rhizoma Fagopyri Dibotryis bullion 300g being used 60% alcoholic solution lixiviate, material and solution ratio is that 1: 10, temperature are that 50 ℃, time are 24 hours;
(3) lixiviating solution is flung to ethanol, adds water to 1500ml, stirs the centrifugal 10min in back, and rotating speed is 5000rpm, abandons deposition, and supernatant with ethyl acetate equal-volume extracted twice, is collected the water raffinate;
(4) LSA-21 macroporous resin column on the water raffinate is at first used 2 times of column volume distilled water washs, the alcoholic solution eluting of 4 column volumes 70% of reuse.With obtaining golden buckwheat high polymeric procyanidin 12.11g after the eluent concentrating under reduced pressure of collecting, the drying, procyanidin content is 57.82%, and average degree of polymerization is 6.7.
Embodiment 21: chemical compound 4 in the present embodiment '-methoxyl group-2 ', 3, the synthesis process and the step of 4-trihydroxy dihydrochalcone are following:
In the 100mL there-necked flask, add 1.66g (0.01mol) 2-hydroxyl-4-methoxyacetophenone, behind the 10mL anhydrous alcohol solution, add 0.966g (0.007mol) K
2CO
3, under the mechanical agitation, slowly drip 1.52g (0.012mol) benzyl chlorine, after being added dropwise to complete, heating reflux reaction, TLC are followed the tracks of and are reacted to 2-hydroxyl-4-methoxyacetophenone point disappearance.Rotary evaporation reclaims ethanol, adds water, ethyl acetate extraction.Extract is washed secondary with 5% NaOH, and the reuse washing is to neutrality, anhydrous MgSO
4Dry.Rotary evaporation boils off solvent and excessive benzyl chlorine.Get the 1.82g white crystal with re-crystallizing in ethyl acetate, be 2-benzyloxy-4-methoxyacetophenone, yield 71% through detecting.
In the 100mL there-necked flask, add 1.38g (0.01mol) 3, the 4-4-dihydroxy benzaldehyde behind the 10mL anhydrous alcohol solution, adds 1.932g (0.014mol) K
2CO
3, under the mechanical agitation, slowly drip 3.04g (0.024mol) benzyl chlorine, after being added dropwise to complete, heating reflux reaction, TLC are followed the tracks of reaction to 3, and 4-4-dihydroxy benzaldehyde point disappears.Rotary evaporation reclaims ethanol, adds water, ethyl acetate extraction.Extract is washed secondary with 5% NaOH, and the reuse washing is to neutrality, anhydrous MgSO
4Dry.Rotary evaporation boils off solvent and excessive benzyl chlorine.Getting 2.15 white crystals with re-crystallizing in ethyl acetate, is 3 through detecting, 4-benzyloxy benzaldehyde, yield 68%.
At N
2In the there-necked flask of stream protection; Add 1.28g (0.005mol) 2-benzyloxy-4-methoxyacetophenone; 1.58g (0.005mol) 3,4-benzyloxy benzaldehyde adds the solution (mass fraction: 14.2%) that is made into by 42mL ethanol and 4.6g KOH under stirring.Heating reflux reaction, TLC follows the tracks of reaction.Finish reaction after the complete obiteration of raw material point, leach the yellow solid matter of separating out in the course of reaction, after water washing; It is 4 '-methoxyl group-2 ' through detection that bullion uses ethyl alcohol recrystallization to obtain yellow acicular crystal; 3,4-three benzyloxy chalcone derivative 2.26g, yield: 81%.
In there-necked flask (band mercury seal), add 1.67g (3mmol) 4 '-methoxyl group-2 ', 3,4 ,-three benzyloxy chalcone derivative are used the 200mL dissolve with ethanol, add 20mL 1mol/L NaOH solution, 0.8g 10%Pd/C catalyst.Behind the enclosed system, feed hydrogen and make mercury column keep 10mmHg.The reaction of room temperature vigorous stirring, TLC detection reaction terminal point.After 1 hour, raw material point disappears, stopped reaction.Remove by filter catalyst, rotation boils off ethanol, transfers pH to neutral with hydrochloric acid.Ethyl acetate extraction, extract concentrate the back recrystallization, obtain pale yellow crystals, are 4 '-methoxyl group-2 ' through detecting, and 3,4-trihydroxy dihydrochalcone 0.59g, yield: 68%.
Embodiment 22: present embodiment chemical compound 2, and 4-dimethoxy-2 ', 5 '-synthesis process and the step of dihydroxy dihydrochalcone is following:
In the 100mL there-necked flask, add 1.52g (0.01mol) 2, the 5-resacetophenone behind the 10mL anhydrous alcohol solution, adds 1.932g (0.014mol) K
2CO
3, under the mechanical agitation, slowly drip 3.04g (0.024mol) benzyl chlorine, after being added dropwise to complete, heating reflux reaction, TLC are followed the tracks of reaction to 2, and 5-resacetophenone point disappears.Rotary evaporation reclaims ethanol, adds water, ethyl acetate extraction.Extract is washed secondary with 5% NaOH, and the reuse washing is to neutrality, anhydrous MgSO
4Dry.Rotary evaporation boils off solvent and excessive benzyl chlorine.Getting the 2.26g white crystal with re-crystallizing in ethyl acetate, is 2 through detecting, 5-benzyloxy 1-Phenylethanone., yield 68%.
At N
2In the there-necked flask of stream protection, add 1.66g (0.005mol) 2,5-benzyloxy 1-Phenylethanone., 0.83g (0.005mol) 2, the 4-dimethoxy benzaldehyde adds the solution (mass fraction: 14.2%) that is made into by 42mL ethanol and 4.6g KOH under stirring.Heating reflux reaction, TLC follows the tracks of reaction.Finish reaction after the complete obiteration of raw material point, leach the yellow solid matter of separating out in the course of reaction, after water washing; Bullion obtains the yellow acicular crystal of 1.94g with ethyl alcohol recrystallization, is 2 through detecting, 4-dimethoxy-2 '; 5 '-benzyloxy chalcone derivative, yield: 81%.
In there-necked flask (band mercury seal), add 1.44g (3mmol) 2,4-dimethoxy-2 ', 5 '-benzyloxy chalcone derivative is used the 200mL dissolve with ethanol, adds 20mL1mol/L NaOH solution, 0.8g 10%Pd/C catalyst.Behind the enclosed system, feed hydrogen and make mercury column keep 10mmHg.The reaction of room temperature vigorous stirring, TLC detection reaction terminal point.After 1 hour, raw material point disappears, stopped reaction.Remove by filter catalyst, rotation boils off ethanol, transfers pH to neutral with hydrochloric acid.Ethyl acetate extraction, extract concentrate the back recrystallization, obtain pale yellow crystals 0.61g, are 2 through detecting, 4-dimethoxy-2 ', 5 '-dihydroxy dihydrochalcone, yield: 68%.
Embodiment 23: 4 among the resulting embodiment 18 Cortex Cinnamomi procyanidin extracts of the inventive method, the embodiment 19 gold buckwheat raw anthocyanin extract embodiment 21 '-methoxyl group-2 '; 3; Among 4-trihydroxy dihydrochalcone and the embodiment 22 2; 4-dimethoxy-2 ', 5 '-the dihydroxy dihydrochalcone makes AGEs and generates inhibition test.
It is following that advanced glycosylation end product of the present invention generates the inhibition test method:
In the test tube that the pH7.4 phosphate buffer is housed, adding cumulative volume is glucose, bovine serum albumin, the NaN of 5mL
3Solution makes its final concentration be respectively 500mmol/L, 50mg/mL and 0.2g/L, adds the above-mentioned thing that tried, and the final concentration that is tried thing is respectively shown in the table 2.The positive matched group of aminoguanidine, its final concentration are 0.1mg/ml, and blank control group is not for adding the nonenzymatic glycosylation system of medicine; After 37 ℃ of lucifuges are hatched 7 days; Take out 3mL detects AGEs with fluorescence detector (excitation wavelength 330nm, emission wavelength 410nm, slit 5nm) fluorescence absorbance F from each pipe.Be calculated as follows suppression ratio IR%=(1-F medicine/F is blank) * 100%.Experimental result sees the following form 2:
The external AGEs of table 2 generates inhibitory action
The external AGEs of Chinese medicine cinnamon extract generates the inhibition experimental result and shows that this extract low dose group effect approaches the positive control aminoguanidine, and middle high dose group effect obviously is superior to the positive control aminoguanidine, and forms the metering dependence; Gold buckwheat raw anthocyanin extract, 4 '-methoxyl group-2 ', 3,4-trihydroxy dihydrochalcone and 2,4-dimethoxy-2 ', 5 '-the external AGEs of dihydroxy dihydrochalcone generates and suppresses effect and also be superior to the positive control aminoguanidine.It should be noted that and tried thing 5 compositions for Cortex Cinnamomi procyanidin extract and gold buckwheat raw anthocyanin extract, tried thing 6 and be 4 '-methoxyl group-2 '; 3,4-trihydroxy dihydrochalcone and 2,4-dimethoxy-2 '; 5 '-compositions of dihydroxy dihydrochalcone, tried thing 7 for Cortex Cinnamomi procyanidin extract and 4 '-methoxyl group-2 ', 3; The compositions of 4-trihydroxy dihydrochalcone is tried thing 8 and is gold buckwheat raw anthocyanin extract and 2,4-dimethoxy-2 '; 5 '-compositions of dihydroxy dihydrochalcone, these four compositionss generate AGEs and suppress effect and obviously be superior to each one matter, show that compositions has good synergism.
Short islet cells insulin secretion test concrete grammar is following: islets of langerhans is divided into gliclazide positive controls and 3 groups of object groups, and every group adds 1ml sugar-free Krebs-Ringer liquid (being called for short K liquid) in 37 ℃, 5%CO
2Hatched in the incubator 30 minutes, and took out centrifugal 1000rpm, 1 minute, abandon supernatant, in each group, add the sugar-free K liquid of 1ml then respectively, hatched 4 hours.Get supernatant, survey insulin content, see table 3 with the rat insulin radioimmunoassay kit.
Table 3 chemical compound is to the insulin secretagogue effect of islet cells
From the visible chemical compound 4 of table 3 '-methoxyl group-2 '; 3, the insulin secretagogue effect of 4-trihydroxy dihydrochalcone maintains an equal level with the positive control gliclazide basically, and chemical compound 2; 4-dimethoxy-2 ', 5 '-the dihydroxy dihydrochalcone obviously is superior to gliclazide; Receive examination group 3 for chemical compound 4 '-methoxyl group-2 ', 3,4-trihydroxy dihydrochalcone and 2; 4-dimethoxy-2 '; 5 '-1: 1 compositions of dihydroxy dihydrochalcone, obviously greater than each unification compound, compositions demonstrates good synergism in its insulin secretagogue effect.
Claims (3)
1. one kind has the compositions that promotes insulin secretion and suppress the advanced glycosylation end product nucleus formation, it is characterized in that this combination
The composition of thing and quality percentage composition are:
Procyanidin extract 5～95%,
Dihydrochalcone 5～95%;
The main component of described procyanidin extract is a procyanidin, and described procyanidin extract extracts from Cortex Cinnamomi or Rhizoma Fagopyri Dibotryis;
The concrete grammar that wherein from Cortex Cinnamomi, extracts procyanidin extract is: after Chinese medicine cinnamon is pulverized, cross 40～60 mesh sieves, obtain Cortex Cinnamomi coarse powder material; This Cortex Cinnamomi coarse powder material with petroleum ether Suo Shi extracting, is volatilized solvent; To press Cortex Cinnamomi powder through the Cortex Cinnamomi powder after the Suo Shi extracting: distilled water=1: 10～3: 10 mass ratio mixes, 50～60 ℃ of stirring and leaching 30～120 minutes; Filter cleaner adds 2～5 times of volume ethanol again, and ice-water bath stirred 30～120 minutes; Filter and remove deposition, reclaim ethanol, get extracting solution; This extracting solution is carried out column chromatography for separation purify, concentrating under reduced pressure, vacuum drying gets procyanidin extract, and wherein the quality percentage composition of procyanidin is 65～75%;
The concrete grammar that wherein from Rhizoma Fagopyri Dibotryis, extracts procyanidin extract is:
A) Rhizoma Fagopyri Dibotryis being crushed to particle diameter is 1～3cm, obtains the Rhizoma Fagopyri Dibotryis bullion;
B) above-mentioned Rhizoma Fagopyri Dibotryis bullion use concentration of volume percent is 40%～90% ethanol water lixiviate, and temperature is 50～70 ℃, and the time is 1～2 day, gets lixiviating solution;
C) above-mentioned lixiviating solution is flung to ethanol, add water to and wave pure half preceding volume, stir the centrifugal 10～20min in back, rotating speed is 3000～5000rpm, abandons deposition, and supernatant with the extraction of organic solvent ethyl acetate equal-volume, is got the water raffinate;
D) with LSA-21 macroporous resin column on the water raffinate, at first use 2～5 times of column volume distilled water washs, the concentration of volume percent of 2～4 column volumes of reuse is 30%～70% ethanol water eluting, collects eluent;
E) with obtaining the golden buckwheat high polymeric procyanidin extract after the eluent concentrating under reduced pressure of collecting, the drying, wherein the quality percentage composition of procyanidin is 55～70%;
Described dihydrochalcone is 4 '-methoxyl group-2 ', 3,4-trihydroxy dihydrochalcone and 2,4-dimethoxy-2 ', 5 '-in the dihydroxy dihydrochalcone one or both.
2. the compositions that has the promotion insulin secretion and suppress the advanced glycosylation end product nucleus formation according to claim 1; It is characterized in that described column chromatography for separation method of purification is: adopt macroporous resin column chromatography; Earlier with 3～5 times of column volume distilled water flushings; Use 30～90% ethanol elutions then, collect eluent.
3. the compositions that has the promotion insulin secretion and suppress the advanced glycosylation end product nucleus formation according to claim 2 is characterized in that described macroporous resin column is: HP20, D101, LSA21 or ADS17.
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| CN101972245B true CN101972245B (en) | 2012-07-04 |
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| CN1706281A (en) * | 2004-12-09 | 2005-12-14 | 桂林莱茵生物制品有限公司 | Health food with subsidiary function of lowering blood sugar and lowering blood fat and its production process |
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| Title |
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| JP特开2002-338844A 2002.11.27 |
| 单俊杰等."抗糖尿病及并发症黄酮类化合物的研究进展".《中国新药杂志》.2008,第17卷(第12期),第998-1006页. |
| 李素梅等."原花青素的研究进展".《黑龙江医药》.2006,第19卷(第3期),第201-202页. |
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