CN105646450A - Compound used as anti-obesity agent - Google Patents

Abstract

The invention relates to a compound used as an anti-obesity agent, and the structure of the compound is shown as formula I in the specification. (formula I).

Description

A kind of compound as antiobesity agent

Technical field

The present invention relates to Food Chemistry field, specifically, the present invention relates to the compound as obesity.

Background technology

Obesity is one of disease the most serious in modern society, and its main cause is the excess ingestion of fat. It is furthermore well known that the excess ingestion of fat not only can produce obesity symptom, but also can produce due to symptoms such as fat diabetes, hyperlipidemia, hypertension, arteriosclerosis. The basis that interior fat type is fat is added the state of in hyperglycemia hypertension dyslipidemias any more than 2, it is referred to as metabolic syndrome (interior fat syndrome), owing to the danger of generation heart disease, apoplexy symptom is significantly high, so being considered problem in recent years. As for fat curative, such as Xenical (Xenical) (registered trade mark) improves medicine commercially available as obesity, Xenical (Xenical) is to utilize lipase inhibiting activity to have the suppression effect from intestinal absorption fat, but report has the side effect such as the increase of fat flushing, defecation frequency, soft stool, diarrhoea, stomachache, it is difficult to say certain safety.

For pre-preventing obesity, although reducing picked-up heat by restricting diet is effective means, but strict nutrition guide must be accepted, be difficult under many circumstances in daily life carry out. Result, it is believed that safety and suppress the fat from diet by body absorption healthily, from treating disease fat and related to this or from salubrious purpose, it is actually useful strategy.

Under this background, it was demonstrated that safety and the exploitation of the effective specific food for health care of human body is received publicity. Up to the present; as the raw-food material suppressing post-prandial serum neutral fat value to raise, by being suppressed the globulin analyte of fat absorption to have the different DG digesting and assimilating characteristic from triacylglycerol by pancreatic lipase, by the eicosapentaenoic of pyloric fat acid

Acid (EPA), docosahexenoic acid (DHA) etc. are sold as specific food for health care.

In addition, lipase inhibiting activity material from plant also day by day receives publicity recently, especially with regard to the Polyphenols with lipase inhibiting activity, report and coordinated the tannin from plant bark, the tannins contained in leguminous plant bean tea Semen Cassiae, flavonoid class and glucosides thereof, main component epigallocatechin gallate (EGCG) and the lipid absorption of L-Epicatechin gallate in green tea suppress food, by green pepper, grow thickly Tricholoma mongolicum Imai, Fructus Cucurbitae moschatae, dance young pilose antler, Sargassum fusiforme (Harv.) Setch, green tea, the lipase inhibitor of the water extract composition of oolong tea etc., with flavone and flavonols, hydroxy benzoic acid class (gallic acid), triterpenoid compound and derivant thereof, the procyanidin of tamarind is the antiobesity agent etc. of effective ingredient. and the lipase inhibitory action of known grape seed extract, from Salacia prinoides (Willd.) DC. polyphenol lipase inhibitory action and to the anti-obesic action of rat, the oolong tea extract anti-obesic action etc. to mice. in addition with about in tea containing a large amount of catechins, the most separated qualification of its composition, lipase inhibitor containing the composition from tea report.It is known that as black tea, the pigment of oolong tea and known theaflavin, proportionally show strong lipase inhibiting activity with the quantity of gallic acid ester group in its molecule. But, the content of these theaflavins, ratio are different because of the kind of tea.

Additionally, alpha-glucosidase inhibiting substances, by suppressing the alpha-glucosidase existed on small intestine epithelium, it is suppressed that delay the decomposition of saccharic to absorb, there is blood glucose value and raise inhibitory action. Therefore, alpha-glucosidase inhibiting substances is useful for various diseases such as the diabetes caused by chronic hyperglycemia, obesity.

Since 1933 find alpha-glucosaccharase enzyme inhibition activity in Fructus Hordei Germinatus composition, it was found that a large amount of alpha-glucosidase inhibiting substances from the plant such as Semen Tritici aestivi, beans. From microbe metabolite, within 1966, isolate the nojirimycin with alpha-glucosaccharase enzyme inhibition activity, and determine its structure. The known 1-DNJ as its analog obtains from the extract of Folium Mori, and it has alpha-glucosaccharase enzyme inhibition activity, discloses the extracting method not making its activity reduce.

Additionally report that the material with 13 Yuans ring cyclitol structures with sulfoxide separated from the extract of the root of salacia reticulata (KothalaHimbutu) has maltase inhibitory activity. Additionally report; as from morning glory, Rhizoma Steudnerae Henryanae root in isolated anthocyanin compound, by after two acidylates generate pelargonidin, cyanidin, peonidin 3-sophoroside-5-glucoside (3-sophoroside-5-glucoside) there is maltase inhibitory activity. In addition confirm the double; two nutgall catechin A (TheasinensinA) of the tea contained in Folium Camelliae sinensis, there is the theaflavin derivant of galloyl, as the proanthocyanidin etc. of construction unit, there is maltase inhibitory activity containing epiafzelechin epicatechol gallate. But, although the theaflavin derivant with galloyl has maltase inhibitory activity, but the content in Folium Camelliae sinensis is 0.1��0.2%, considerably less.

Report that the theaflavin of black tea and the catechin of green tea have alpha-glucosaccharase enzyme inhibition activity (non-patent literature 8); and confirm; catechin there are the 3-0-EGCG (hereinafter referred to as " EGCG ") of galloyl, epicatechin-3-O-gallate active on 3; theaflavin-3-O-epicatechol gallate, theaflavin-3 in theaflavins, 3 '-two-O-epicatechol gallate are active. About the alpha-glucosaccharase enzyme inhibition activity of black tea, its separator is analyzed, it is known that the high molecular component being undertaken being polymerized by fermenting also has activity.

On the other hand, it is known that in the sweat manufacturing black tea, oolong tea, under the effect of the enzyme such as polyphenol oxidase of Folium Camelliae sinensis, the Polyphenols generation condensation such as catechin or gallic acid, form the compound with benzotropolone ring.

In report tea except theaflavin, there is also substantial amounts of containing benzotropolone cycle compound. Such as report, red amphyl apoptosis-inducing, table tea luteolin class prepare method and the existence etc. in black tea for manufacture method or the enzymatic as the trimerical Theadibenzotropolone A (TheadibenzotropoloneA) of theaflavin of food. Furthermore know that the various anti-inflammatory effect containing benzotropolone cycle compound. But, for outside theaflavins, table tea luteolin class containing benzotropolone cycle compound, still do not know that its lipase inhibitory action relevant to fat absorption and blood glucose value raise the alpha-glucosaccharase enzyme inhibition that inhibitory action is relevant.

Summary of the invention

Present invention aim at providing a kind of compound suppressing obesity that can be used in food, it is with shown in Formulas I structure:

I��

As the inhibitor of the antiobesity agent of the present invention, by containing the extraction compound from Folium Camelliae sinensis, the lipase inhibiting activity that display is excellent. The lipase inhibitor of the present invention may use and includes not damaging fragrance, hobby property height and the various uses to reduce the diet product for the purpose of neutral fat, promotion health. In order to suppress the fat absorption in diet, it is desirable to absorb when having dinner simultaneously, the beverage after being strengthened by the effective ingredient obtained from tea is significant. Especially by strengthening these compositions, it is possible to provide by anti-obesic action, promote the beverage for the purpose of health.

As the inhibitor of the antiobesity agent of the present invention, with in the past known to compared with the alpha-glucosidase of natural goods, using the decomposition that can suppress on a small quantity from the starch of diet, the sugar of polysaccharide, it is suppressed that absorb. And because any one compound be all teas contains catechin, polyphenol oxide, so fragrance, excellent in safety, can taken long-term.

Additionally, the antiobesity agent of the present invention, owing to containing the compound as the composition from the veteran tea of diet, so can be used for the medical composition of safety height, side effect reduction.

Embodiment

The invention will be further described by the examples below. The method described in the embodiment of the present invention that it should be understood that is only used for illustrating the present invention rather than limitation of the present invention, under the concept thereof of the present invention, the simple modifications of preparation method of the present invention is broadly fallen into the scope of protection of present invention. The all raw materials used in embodiment and solvent are all purchased from SigmaBiochemicalandOrganicCompoundsforResearchandDiagnos ticClinicalReagents company; Black tea is common commercial products.

Embodiment 1: the preparation of Formulas I chemical combination

(1) by black tea dissolving crude product in proper amount of sodium carbonate aqueous solution, complete solution after being sufficiently stirred for, is dissolved. Drip acetic acid again and be about 6-8 to solution ph; Being subsequently adding the activated carbon of the 10-40% accounting for crude product weight and the neutral alumina of 20-40%, 10-20 DEG C of stirring decolouring 15-30min filters, and collects filtrate;

(2) being slowly added to acetic acid in above-mentioned filtrate under stirring, temperature control 10-20 DEG C stirring is 6.0 �� 0.2 to solution ph, and stirring precipitates out precipitation also growing the grain 30 minutes; It is further continued for dropping acetic acid, is 5.6��5.8 to pH value of solution. Slow cooling to 5 DEG C, about 30 minutes used times; Stirred crystallization 30 minutes at this temperature; It is further continued for being cooled to 0��2 DEG C, stirred crystallization 1 hour. Collect by filtration precipitation; And with a small amount of acetone, filter cake is carried out drip washing.

(3) after filter cake being taken out, at 25��30 DEG C, lower vacuum drying 4h, obtain flaxen compound of formula I.

¹HNMR(300MHz,CDCl₃):��8.69(s,1H),7.49(s,1H),7.36(s,1H),6.94(s,1H),6.50(s,1H),4.25(t,J=4.2Hz,2H),3.78(s,3H),3.68(s,3H),3.26(m,2H),3.08(m,1H),2.84(m,2H),2.47(m,4H),1.73(m,7H),1.46(s,9H).

Embodiment 2: biological activity test

The mensuration of lipase active, by using the oleate (4-MUO of fluorescence 4-methyl umbelliferone in substrate; Sigma company system), the fluorescence measuring the 4-methyl umbelliferone by reacting generation is implemented. During mensuration, buffer uses containing 150mMNaCl, 1.36mMCaCl₂13mMTris-HCl (pH8.0). 4-MUO as substrate, enzymatic determination is supplied after diluting 4000 times with above-mentioned buffer after the DMSO solution of formation 0.1M, in addition lipase, same use above-mentioned buffer supplies enzymatic determination after porcine pancreatic lipase (Sigma company system) is made 400U/ml solution.

Enzyme reaction is under 25 DEG C of conditions, after adding and mix the 4-MUO buffer soln of 50 �� l, 25 �� l distilled water (or sample aqueous solution), starts by adding 25 �� l lipase buffer solns on 96 hole microwell plates. After carrying out reaction in 30 minutes, the 0.1M citrate buffer solution (pH4.2) adding 100 �� l makes the stopping of reaction. The fluorescence (excitation wavelength 355nm, wavelength of fluorescence 460nm) by reacting the 4-methyl umbelliferone generated is measured with fluorescence microplate detector (Labsystem company FluoroskanAsentCF).

The inhibitory activity of tested sample, suppresses the sample size IC needed for 50% as the activity relative to comparison (distilled water)₅₀(��M) and obtain. The lipase known activity of compound of formula I is 0.202.

Claims (2)

1. the compound being used as antiobesity agent, it is characterised in that shown in Formulas I:

I��

2. the compositions of an obesity, it is characterised in that containing auxiliary agent acceptable in compound of formula I and food.