CN102030810B - Gallic acid tea sapogenol ester as well as preparation method and application thereof - Google Patents
Gallic acid tea sapogenol ester as well as preparation method and application thereof Download PDFInfo
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- CN102030810B CN102030810B CN2010105159637A CN201010515963A CN102030810B CN 102030810 B CN102030810 B CN 102030810B CN 2010105159637 A CN2010105159637 A CN 2010105159637A CN 201010515963 A CN201010515963 A CN 201010515963A CN 102030810 B CN102030810 B CN 102030810B
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Abstract
The invention discloses a gallic acid tea sapogenol ester as well as a preparation method and application thereof. The gallic acid tea sapogenol ester has a structure shown in the formula I and is prepared by the following steps of: reacting benzyl bromide and gallic acid to connect benzyl groups to carboxyl groups of the gallic acid and protect the carboxyl groups of the gallic acid; then, adding tea sapogenins for performing esterification with the gallic acid in the presence of a catalyst A; and finally adding a benzyl deprotection agent for removing the benzyl groups from the gallic acid in the presence of a catalyst B to obtain the gallic acid tea sapogenol ester shown in the formula I. The preparation method of the gallic acid tea sapogenol ester is simple and convenient for industrialized production, and the prepared gallic acid tea sapogenol ester has little toxicity and higher antioxidation and radical removing performances and overcomes the defect of low antioxidation activity of tea saponins.
Description
Technical field
The present invention relates to the food and medicine field, be specifically related to gallic acid tea sapogenol ester and preparation method thereof, with and as the application of inhibitor.
Background technology
Superoxide is often by free-radical generating.Radical can cause the composition oxidation in the food to destroy and go bad.The unstable radical that produces in the body metabolism process is piled up in cell, will cause that unsaturated fatty acids is oxidized to superoxide, forms lipofuscin, and cell and important component such as DNA, protein and enzyme etc. is changed or destruction.Human disease more than 90% is relevant with radical, and especially diseases such as cardiovascular and cerebrovascular diseases, nerve degeneration class, tissue injury are brought out by excessive free radicals.
For a long time; Rotten in order to prevent Food Oxidation; People use artificial synthetic antioxidant BHT, BHA, TBHQ, PG etc. always, but there is health risk in the inhibitor of synthetic, possibly cause lesions of liver and kidney, cardiovascular disorder; And the possibility induced tumor, developed countries such as Japan, the U.S. have been used as strict restriction to making of above-mentioned synthetic inhibitor.
Because many natural products have anti-oxidant activity, and have no side effect, therefore from natural product, finding and utilizing inhibitor has been a kind of inevitable trend.
Theasaponin is to be present in a kind of main pentacyclic triterpene compound in tea seed or the tea seed, is made up of sapogenin, sugared body and organic acid three parts.China is the country of high-yield tea-oil, and the content of saponin accounts for 12% in the tea seed, has bigger exploitation and is worth.
Theasaponin has anti-oxidant activity.Li Ping etc. (inquire into the provide protection and the mechanism thereof of rat heart damage due to the anoxic reoxygenation by Sasanguasaponin; Herbal medicine; 2000; 31 (11): find that 841～843) oil tea saponin can make the increased activity of myocardium superoxide dismutase (SOD), Thiadiazolidine isomerase (GSH-Px), the generation of lipid peroxidation product mda MDA reduces.
(Anti-inflammatory and antioxidant property of saponins of tea (Camellia sinensis (L) O.Kuntze) root extract such as Sur P; Phytother Res; 2001,15 (2): 174～176) find the theasaponin that from Tea root, extracts; External anti-inflammatory and antioxygenation are arranged, and verified the antioxygenation of these compositions with xanthine-xanthine oxidase system.
(the anti-oxidant and removing radical ability preliminary study of oil tea total saponins such as Lv Xiaoling; Food science; 2005; 26 (11): find that 86～90) the oil tea total saponins has significant oxidation-resistance and to the restraining effect of ribodesose oxidative damage, the active oxygen radical that chemical reaction is generated has significant scavenging(action).
(sasanguasaponin is to the influence of hyperlipemia card rat model high density lipoprotein cholesterol and subfraction thereof for Chen Lifeng etc.; Pharmacology and Clinics of Chinese Materia Medica; 1998,14 (4): find that 13～16) sasanguasaponin can obviously reduce the level of serum total cholesterol (TCh), triglyceride level (TG), low density lipoprotein cholesterol (LDL); Significantly do not change HDL concentration, reduce atherogenic index (Ai); Sasanguasaponin effect for reducing fat intensity is equivalent to clofibrate 250mg/kg in the time of 50 to 100mg/kg.
Though theasaponin has certain antioxygenation, its structure has surfactivity, be prone to bubble, and sugared structure easy oxidation discoloration, instability is unfavorable for it and uses, and has also influenced its antioxidant effect in vivo.
Summary of the invention
The shortcoming that primary and foremost purpose of the present invention is to overcome prior art provides the theasapogenol verivate gallic acid tea sapogenol ester that has than strong antioxidant action with not enough.
Another object of the present invention is to provide the preparation method of above-mentioned gallic acid tea sapogenol ester.
A purpose more of the present invention is to provide the application of above-mentioned gallic acid tea sapogenol ester.
The object of the invention is realized through following technical proposals:
Gallic acid tea sapogenol ester has suc as formula the structure shown in the I,
Wherein, R is H or galloyl, and having a R at least is galloyl.
The preparation method of above-mentioned gallic acid tea sapogenol ester is characterized in that may further comprise the steps:
Bromobenzyl and gallic acid reaction, benzyl is connected on the carboxyl of gallic acid, get up the carboxy protective of gallic acid; Then, under the effect of catalyst A, add theasapogenol and gallic acid generation esterification; At last, under the effect of catalyst B, add the benzyl deprotection agent, slough the benzyl on the gallic acid, obtain suc as formula the gallic acid tea sapogenol ester shown in the I.
Said gallic acid consumption is 1～5 times of molar weight of theasapogenol, and the bromobenzyl consumption is 3 times of molar weights of gallic acid, and the temperature of reaction of gallic acid and bromobenzyl is 120～140 ℃, and the reaction times is 8～16h.
Said theasapogenol is any in the theasapogenol that from tealeaves, tea seed or tea seed, separate to obtain.
Said catalyst A is N, the mixture of N-NSC 57182 (DCC) and 4-dimethylamino pyridine (DMAP), wherein; The DCC consumption is the equimolar amount of gallic acid; The DMAP consumption is 5～10% of a theasapogenol quality, and esterification reaction temperature is 20～30 ℃, reaction times 8～16h.
Said catalyst B is a palladium carbon, and the benzyl deprotection agent is a hydrogen.
The application of above-mentioned gallic acid tea sapogenol ester is characterized in that: said gallic acid tea sapogenol ester adds in the food as inhibitor.
The application of above-mentioned gallic acid tea sapogenol ester is characterized in that: said gallic acid tea sapogenol ester is used to prepare the pharmaceutical prepn of anti-oxidant or Green Tea Extract.
Said gallic acid tea sapogenol ester can be processed the pharmaceutical prepn of anti-oxidant or Green Tea Extract with pharmaceutical excipient or pharmaceutically compatible medicine.
Said pharmaceutical prepn is any of external application, oral or injecting drug use formulation.
Said pharmaceutical prepn is folk prescription or the compound preparation that contains gallic acid tea sapogenol ester.
The sugared body portion of theasaponin is removed, the theasapogenol Stability Analysis of Structures of acquisition, non-foaming, still have anti-oxidant activity, again it is connected with the Nutgalls base, the theasapogenol verivate of deriving new improving its stability simultaneously, can strengthen its antioxidant effect.
The present invention has following advantage and effect with respect to prior art:
(1) gallic acid tea sapogenol ester good stability of the present invention, anti-oxidant higher than theasaponin with the removing free radical activity, and toxicity is little.
(2) preparation technology of gallic acid tea sapogenol ester of the present invention is simple, is convenient to suitability for industrialized production.
Embodiment
Below in conjunction with embodiment the present invention is described in further detail, but embodiment of the present invention is not limited thereto.
Embodiment 1
Gallic acid (34.7g) adds 300mL toluene, is warming up to 120 ℃, slowly drips the bromobenzyl (105g) of 3 times of molar weights of gallic acid, stirring reaction 8h; After being cooled to 20 ℃, add theasapogenol solid 100g, DCC (42.2g), DMAP (5g), 20 ℃ of stirring reaction 8h, the elimination insolubles adds saturated aqueous common salt 300mL washing 3 times; Reaction product is placed pressure reaction still, is catalyzer with 10% palladium carbon, feeds hydrogen 3h.Use the 600mL alcohol extraction, obtain product 63g behind the recovery ethanol.
Structural analysis to product shows that MS:m/z 642; Elementary compositionly be: C69.13%, H8.47%, O22.40%, its molecular formula is C
37H
54O
9,
1H-NMR with
13The hydrogen of C-NMR and carbon signal show has increased by 1 phenyl ring, 1 carbonyl carbon and 3 hydroxyls than theasapogenol.The proof final product is single gallic acid tea sapogenol ester, and its structural formula is as follows:
Embodiment 2
Gallic acid (69.4g) adds 300mL toluene, is warming up to 125 ℃, slowly drips the bromobenzyl (210g) of 3 times of molar weights of gallic acid, stirring reaction 10h; After being cooled to 22 ℃, add theasapogenol solid 100g, DCC (84.4g), DMAP (6g), 22 ℃ of stirring reaction 10h, the elimination insolubles adds saturated aqueous common salt 300mL washing 3 times; Reaction product is placed pressure reaction still, is catalyzer with 10% palladium carbon, feeds hydrogen 3h.Use the 600mL alcohol extraction, obtain product 73g behind the recovery ethanol.
Structural analysis to product shows that MS:m/z 794; Elementary compositionly be: C66.48%, H7.35%, O26.17%, its molecular formula is C
44H
58O
13,
1H-NMR with
13The hydrogen of C-NMR and carbon signal show has increased by 2 phenyl ring, 2 carbonyl carbon and 6 hydroxyls than theasapogenol.The proof final product is a digallic acid tea sapogenol ester, and its structural formula is as follows:
Embodiment 3
Gallic acid (104.1g) adds 400mL toluene, is warming up to 130 ℃, slowly drips the bromobenzyl (315g) of 3 times of molar weights of gallic acid, stirring reaction 12h; After being cooled to 26 ℃, add theasapogenol solid 100g, DCC (126.6g), DMAP (8g), 26 ℃ of stirring reaction 12h, the elimination insolubles adds saturated aqueous common salt 400mL washing 3 times; Reaction product is placed pressure reaction still, is catalyzer with 10% palladium carbon, feeds hydrogen 3h.Use the 600mL alcohol extraction, obtain product 89g behind the recovery ethanol.
Structural analysis to product shows that MS:m/z 946; Elementary compositionly be: C64.68%, H6.60%, O28.72%, its molecular formula is C
51H
62O
17,
1H-NMR with
13The hydrogen of C-NMR and carbon signal show has increased by 3 phenyl ring, 3 carbonyl carbon and 9 hydroxyls than theasapogenol.The proof final product is three gallic acid tea sapogenol esters, and its structural formula is as follows:
Embodiment 4
Gallic acid (138.8g) adds 500mL toluene, is warming up to 135 ℃, slowly drips the bromobenzyl (420g) of 3 times of molar weights of gallic acid, stirring reaction 14h; After being cooled to 28 ℃, add theasapogenol solid 100g, DCC (168.8g), DMAP (9g), 28 ℃ of stirring reaction 14h, the elimination insolubles adds saturated aqueous common salt 500mL washing 3 times.Reaction product is placed pressure reaction still, is catalyzer with 10% palladium carbon, feeds hydrogen 3h.Use the 800mL alcohol extraction, obtain product 126g behind the recovery ethanol.
Structural analysis to product shows that MS:m/z 1098; Elementary compositionly be: C63.38%, H6.05%, O30.57%, its molecular formula is C
58H
66O
21,
1H-NMR with
13The hydrogen of C-NMR and carbon signal show has increased by 4 phenyl ring, 4 carbonyl carbon and 12 hydroxyls than theasapogenol.The proof final product is four gallic acid tea sapogenol esters, and its structural formula is as follows:
Embodiment 5
Gallic acid (173.5g) adds 500mL toluene, is warming up to 140 ℃, slowly drips the bromobenzyl (525g) of 3 times of molar weights of gallic acid, stirring reaction 16h; After being cooled to 30 ℃, add theasapogenol solid 100g, DCC (212g), DMAP (10g), 30 ℃ of stirring reaction 16h, the elimination insolubles adds saturated aqueous common salt 500mL washing 3 times; Reaction product is placed pressure reaction still, is catalyzer with 10% palladium carbon, feeds hydrogen 3h.Use the 800mL alcohol extraction, obtain product 135g behind the recovery ethanol.
Structural analysis to product shows that MS:m/z 1250; Elementary compositionly be: C62.39%, H5.64%, O31.97%, its molecular formula is C
65H
70O
25,
1H-NMR with
13The hydrogen of C-NMR and carbon signal show has increased by 5 phenyl ring, 5 carbonyl carbon and 15 hydroxyls than theasapogenol.The proof final product is five gallic acid tea sapogenol esters, and its structural formula is as follows:
Embodiment 6
Gallic acid tea sapogenol ester is to the anti-oxidant experiment of edible vegetable oil
Method: take by weighing the gallic acid tea sapogenol ester 50mg that embodiment 1 prepares; With ethanol 20mL dissolving, add 250g edible vegetable oil, after vibration mixes; Place in 60 ± 2 ℃ of thermostat water baths; The 3g that takes a sample at regular intervals measures its peroxide value POV (meq/kg) with iodimetry,iodometry (GB/T 5538-1995 " oil peroxidation pH-value determination pH method "), and calculates inhibiting rate IE.Adding the positive control group of theasapogenol, be the blank group with the grease of application of sample not.
The result: behind the 24h, the POV of blank group is 15.24.meq/kg, and positive controls is 5.87meq/kg, and gallic acid tea sapogenol ester group is 4.53meq/kg.The inhibiting rate of positive controls and gallic acid tea sapogenol ester is respectively 61.48% and 70.28%, explains that gallic acid tea sapogenol ester of the present invention is superior to theasapogenol to greasy oxidation-resistance.
Embodiment 7
The experiment of the external removing radical of gallic acid tea sapogenol ester ability
Method: adopt 1, bitter phenylhydrazine (DPPH) free radical method of 1-phenylbenzene-2-is measured.Take by weighing the DPPH of 4mg, dissolve with methanol with 95% and constant volume are to 100mL.The methanol solution and the 3mL DPPH solution of the gallic acid tea sapogenol ester that the embodiment 2 of 1mL different concns is prepared add respectively in the test tube, shake up, and room temperature leaves standstill behind the 20min measures absorbance A in the 517nm place
1The methanol solution and the zeroing of 3mL 95% methanol solution of the gallic acid tea sapogenol ester of 1mL different concns (respectively with).Measure 1mL95% ethanol and 3
The mixed absorbance A of mL DPPH solution 0 is made positive control as negative control with Vc, and each concentration is parallel to be done 3 times, calculates clearance rate according to formula:
The result: gallic acid tea sapogenol ester has remarkable scavenging(action) to the DPPH radical, and its removing ability increases and increases along with concentration.During greater than 50 μ g/mL, the removing effect of its radical is superior to Vc at dosage.The result sees table 1.
Table 1 gallic acid tea sapogenol ester is to the clearance rate (
n=3) of DPPH radical
Embodiment 8
Gallic acid tea sapogenol ester is to the antioxygenation experiment of mouse aging
Method: get 60 mouse (Kunming kinds; Available from Traditional Chinese Medicine University Of Guangzhou's animal center); Body weight (20 ± 2) g is divided into normal control group, model group, positive controls (VE) and gallic acid tea sapogenol ester group (the gallic acid tea sapogenol ester for preparing with embodiment 3, embodiment 4, embodiment 5 respectively) at random.Each experimental group is irritated the stomach relative medicine, in the time of administration, and positive controls, model group and the gallic acid tea sapogenol ester group mouse nape every day subcutaneous injection 5%D-of portion semi-lactosi 0.5mL; Control group injection equivalent saline water; After 6 weeks of modeling, eye socket is got blood, after taking off cervical vertebra and causing death; Separate liver and cerebral tissue, press the testing cassete working method and measure and calculate serum and tissue SOD, GSH-PX vigor and MDA content.
The result: due to the D-semi-lactosi in aging model mice serum, liver and the cerebral tissue MDA content obviously raise the activity decline of relevant scavenger enzyme SOD of radical and GSH-Px.Gallic acid tea sapogenol ester can obviously reduce the metabolic end product MDA of MDA in mouse aging serum, liver and the cerebral tissue, and the activity of SOD and GSH-Px raises.The above-mentioned effect of gallic acid tea sapogenol ester shows that it has strengthened the anti-oxidant function of body, has anti-aging effects.The result sees table 2, table 3, table 4.
Table 2 gallic acid tea sapogenol ester is to the influence (
n=10) of MDA content in mouse aging serum, liver and the brain
Table 3 gallic acid tea sapogenol ester is to the active influence of SOD in mouse aging serum, liver and the brain (
n=10)
Table 4 gallic acid tea sapogenol ester is to the active influence of GSH-Px in mouse aging serum, liver and the brain (
n=10)
Embodiment 9
Get the gallic acid tea sapogenol ester 10g of embodiment 1～5, add the 200mL dissolve with ethanol, promptly get the ethanolic soln of 5% gallic acid tea sapogenol ester after the filtration, can be used as oil antioxidant.
Embodiment 10
Get the gallic acid tea sapogenol ester 10g of embodiment 1～5, mix by mixture 30g, 1% Magnesium Stearate of 7: 2: 1 compositions, process tablet through tabletting machine with starch, lactose, crystalline cellulose.
Embodiment 11
Get the theasapogenol 10g that embodiment 1～5 makes, add medical starch 30g, mix, wet granulation is regulated with ethanol, makes loose particles and crosses 20 mesh sieves, dries.Drying is filled capsules afterwards, promptly gets the capsule of gallic acid tea sapogenol ester.
Embodiment 12
Get the gallic acid tea sapogenol ester 10g of embodiment 1～5, after Spheron MD 30/70 1000mL dissolving, pour into bottle, process injection.
The foregoing description is a preferred implementation of the present invention; But embodiment of the present invention is not restricted to the described embodiments; Other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; All should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (5)
1. gallic acid tea sapogenol ester, it is characterized in that: said gallic acid tea sapogenol ester has suc as formula the structure shown in the I:
Wherein, said R is H or galloyl, and having a R at least is galloyl.
2. the application of the said gallic acid tea of claim 1 sapogenol ester is characterized in that: said gallic acid tea sapogenol ester is as food antioxidant.
3. the application of the said gallic acid tea of claim 1 sapogenol ester is characterized in that: said gallic acid tea sapogenol ester is used to prepare the pharmaceutical prepn of anti-oxidant or Green Tea Extract.
4. according to the application of the said gallic acid tea of claim 3 sapogenol ester, it is characterized in that: said gallic acid tea sapogenol ester and pharmaceutical excipient or pharmaceutically compatible medicine are processed the pharmaceutical prepn of anti-oxidant or Green Tea Extract.
5. according to the application of the said gallic acid tea of claim 3 sapogenol ester, it is characterized in that: said pharmaceutical prepn is any of external application, oral or injecting drug use formulation.
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| CN101392015A (en) * | 2008-07-22 | 2009-03-25 | 沈阳药科大学 | Triterpene saponin in camellia seeds, preparation method and medical use thereof |
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| CN101392015A (en) * | 2008-07-22 | 2009-03-25 | 沈阳药科大学 | Triterpene saponin in camellia seeds, preparation method and medical use thereof |
Non-Patent Citations (2)
| Title |
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| Kazuko YOSHIKAWA, et al..Antisweet Natural Products. XII. Structures of Sitakisosides XI-XX from Stephanotis lutchuensis KOIDZ. var. japonica.《Chem. Pharm. Bull》.1997,第45卷(第1期),62-67. * |
| 王永奇等.药用山茶属植物的研究.《大连大学学报》.2006,第27卷(第4期),47-55,58. * |
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