CN101543546B - Antioxidative substance and composition and use thereof - Google Patents
Antioxidative substance and composition and use thereof Download PDFInfo
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- CN101543546B CN101543546B CN200810035353XA CN200810035353A CN101543546B CN 101543546 B CN101543546 B CN 101543546B CN 200810035353X A CN200810035353X A CN 200810035353XA CN 200810035353 A CN200810035353 A CN 200810035353A CN 101543546 B CN101543546 B CN 101543546B
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Abstract
The invention belongs to the technical field of medicaments, and in particular relates to an antioxidative substance and a composition and use thereof. The invention provides an extract from dictamnus dasycarpus, which has good antioxidation, can be used for preparing antioxidative medicaments, health care foods or cosmetics, and has the advantages of obvious curative effect, low price, convenient use and the like.
Description
Technical field
The invention belongs to medical technical field, relate in particular to a kind of antioxidant and compositions thereof and purposes.
Background technology
All physiological changies of the health that old and feeble expression occurred along with time lapse, and old and feeble situation is different because of individual instances with speed, and be subject to the impact of many reasons.Even in body one by one, old and feeblely also show different situations for each organ, more specifically, the function of each Organ and tissue changes in time, and this situation is because the change of cell function causes.For example, the damage of cranial nerve cell causes cognitive decline, and the damage of subcutaneous fat cells can cause the loss of skin elasticity, and the loss that the Rhizoma Imperatae melanocyte is produced the melanin ability can cause poliosis, etc. this type of situation.
Free radical and aging have obvious relation, and some scientists think that free radical is to cause old and feeble main cause.The oxygen-derived free radicals random disruptions that in common metabolic processes, produces the cell component such as lipid, protein, sugar or DNA, cause the oxidative stress of cell or tissue, not only can cause thus (the Halliwell such as various diseases, the cardiovascular disease such as cerebral hemorrhage and arteriosclerosis, the chronic inflammatory disease such as rheumatism, autoimmune disease such as cancer, B and Gutteridge, J.M.C, Biochem.J., 1984,219,1-14; Freeman, B.A. and Grapo, J.D., Lab Invest, 1982,47,412-426; Ames, B.N., Science, 1983,221,1256-1264; Fridovich, I., Arch.Biochem.Biophys., 1986,247,1-11; Vishwanath, M.S., Nutrition in ClinicalPractice, 1995,10,19-25), in addition, the diseases such as free radical and gastritis, peptic ulcer, primary glomerulopathy, diabetes, bronchial asthma, emphysema, paralysis agitans have close relationship.
Therefore, remove in time too much free radical in the body, reduce the accumulation of free radical and the generation of peroxidization, can play infringement, the resist the disease of defence free radical, the effect of slow down aging.
Up to now, ascorbic acid, alpha-tocopherol or SOD are for the preparation of the cosmetics of protection skin or as the medical supplies of free radical scavenger.But its price is high, and because the unstability of chemical mixture, and make its effect uncertain.Therefore, the common objective in medical supplies, foods and cosmetics industry is to develop the material that namely can effectively remove again safely free radical.
Shaggy-fruited dittany (Dictamnus dasycarpus Turcz.) is Rutaceae shaggy-fruited dittany platymiscium, is perennial herb, and Herb has special penetrating odor, and the base portion lignifying is up to 1 meter.The radical bar is grown thickly, and the strong sheep abnormal smells from the patient of having a strong smell is arranged, yellowish white, close living blister oil drop.Stem is upright, and the bottom is closely wooden, usually without hair.The imparipinnate leaf alternate, 5～13 on lobule, stockless, to life, avette to oval on rachis, long 3.5～9 centimetres, wide 2～4 centimetres, the sharp point of tip, there is serration at the edge.Raceme, mixed white glandular hair and the black glandular hair of giving birth to of floral axis and bennet; Floral white or pale red; Sepal 5; Petal 5, below 1 have a down dip and slightly long; Stamen 10 stretches out outside the petal.Capsule 5 splits, and there is long beak shape tip on the rip-panel top, the close living sepia oil drop in surface and glandular hair.Its root bark is called Cortex Dictamni, and different name is northern Cortex Dictamni.Control the diseases such as wind heat sore, scabies, itchy skin eruption, rheumatic arthralgia, jaundice.
Mainly contain the chemical constituents such as alkaloid, flavonoid, terpenoid in the Cortex Dictamni.Wherein, alkaloid comprises .beta.-fagarine, dictamine, γ-.gamma.-fagarine etc.; Terpenoid Bao Kuo fraxinellone, limonin, obacunone, dictamnolactone, dasycarpuside A, dasycarpuside B etc.; Flavonoid comprises luteolin, 3`-O-methyl Taxifolin, 5,7,4`-trihydroxy-3`-methoxyl group isoflavone etc.In recent years, the people such as Du Chengfang isolate 3 noval chemical compounds first from the ethanol extraction of Cortex Dictamni: kihadinin B, Wogonin, fraxinellonone (Du Chengfang, Yang Xinxin, Tu Pengfei. the chemical constitution study of Cortex Dictamni. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2005,30 (21): 1663-1666).The people such as Yoon isolate the degradation compound of 4 new limonins from the methanolic extract of Cortex Dictamni, be respectively: 9 α ,-Qiang Ji fraxinellone-9-O-β-d-glucosides, dictamnusine, dictamdiol A and dictamdiol B (Yoon JS, Sung SH, Kim YC.Neuroprotective Limonoids of Root Bark of Dictamnus dasycarpus, J Nat Prod.2008 Jan 17).
Modern pharmacology studies show that Cortex Dictamni has antiinflammatory, contracting blood vessel, regulates the effects such as immune.The people such as Lv Jinsheng study the Cortex Dictamni ethanol extract, find that its xylol causes the swelling of mice auricular concha acute inflammation, Ovum Gallus domesticus album induced mice foot and opens up swelling and acetic acid induced mice abdominal cavity capillary permeability and increase and all have significant inhibitory action, and inhibitory action continues the long period.In the test take rat as object, the foot due to Cortex Dictamni ethanol extract on Carrageenan or the Ovum Gallus domesticus album is opened up swelling and has also been shown stronger inhibitory action, shows that the Cortex Dictamni ethanol extract has significant antiinflammatory action.The Cortex Dictamni ethanol extract can obviously promote macrophage activation, shorten the inflammation cycle (Lv Jinsheng, Wu Wei, Meng Desheng etc. the research of Cortex Dictamni ethanol extract antiinflammatory and analgesic activity. Chinese pharmacists .2003; 6 (1): 16-18).The people such as Chang studies show that, 2-methoxyl group-4-phenylacetate 1-o-α-rhamnopyranosyl-β-pyranglucoside and 2-methoxyl group-4-phenol 1-o-α-rhamnopyranosyl-β-pyranglucoside is at external inhibitory action (the Chang J that shows significantly the T cell proliferation, Xuan LJ, Xu YM, Zhang JS.Cytotoxic terpenoid andimmunosuppressive phenolic glycosides from the root bark of Dictamnusdasycarpus.Planta Med, 2002,68 (5): 425-429).
Therefore, up to the present, there is not bibliographical information shaggy-fruited dittany extract to have antioxidation, antidotal effect.The present invention is initiative achievement in research.
Summary of the invention
Technical problem to be solved by this invention provides a kind of new material with antioxidation and/or anti-aging effects, the disease that it can prevent effectively or treatment is relevant with free radical.
In order to solve the problems of the technologies described above,
In a first aspect of the present invention, a kind of antioxidant is provided, it is characterized in that this material contains the water-soluble solution extract of shaggy-fruited dittany (Dictamnus dasycarpus Turcz.).
In a preference, the water-soluble solution extract of described shaggy-fruited dittany is Cortex Dictamni extract.
In a preference, the water-soluble solution extract of described shaggy-fruited dittany is the Cortex Dictamni total alkaloids extract.
In another preference, described water-soluble solution one of is selected from water, methanol aqueous solution, ethanol water, aqueous propanol solution, the butanols aqueous solution or their combination, wherein is preferably the 50-80% ethanol water, most preferably is 70% ethanol water.
In another preference, described antioxidant, it is characterized in that, this antioxidant contains dictamine (dictamnine), γ-.gamma.-fagarine (γ-fagarine), front .beta.-fagarine (preskimmianine), .beta.-fagarine (skimmianine), dasycarpamin (dasycarpamin), trigonelline (trigonelline), choline (choline), O-ethyl-fall-dictamine (O-ethylnordictamnine), (O-ethylnor-γ-fagarine), O-ethyl-fall-.beta.-fagarine (O-ethylnorskimmianine), different speckle boil in the forest-grass alkali (isomaculosidine) one or more to O-ethyl-fall-γ-.gamma.-fagarine.
In a second aspect of the present invention, a kind of antioxidant compositions is provided, described compositions contains:
(a) contain said extracted thing as the 1-99% weight portion of active component;
(b) pharmaceutically acceptable carrier.
In another preference, described antioxidative pharmaceutical composition comprises other antioxidant, such as vitamin E, vitamin C, beta-carotene, superoxide dismutase (SOD), glutathion, flavonoid, Saponin class, ubiquinone
10, trace element such as polyphenols, phospholipid, lecithin and selenium, germanium etc., to strengthen the antioxidation effect of compositions.Described polyphenols is selected from phenolic acid, flavonoid, lignan, coumarin or tannin.
In another preference, the salt that described Cortex Dictamni total alkaloids extract can form with mineral acid or organic acid is for example with the salt of hydrochloric acid, bromine hydracid, iodine hydracid, sulphuric acid, nitric acid, phosphoric acid, acetic acid, maleic acid, fumaric acid, the acid of Chinese holly edge, citric acid, oxalic acid, succinic acid, tartaric acid, malic acid, mandelic acid, trifluoroacetic acid, pantothenic acid, methanesulfonic acid and p-methyl benzenesulfonic acid formation.
In another preference, the dosage form of described pharmaceutical composition is selected from: injection, injectable sterile powder, tablet, capsule, spirit, powder, granule, syrup, solution, tincture, aerosol, powder spray or suppository.
In a third aspect of the present invention, a kind of health-care food composition or cosmetic composition are provided, it is characterized in that it contains antioxidant extract of the present invention.
In a preference, described antioxidant extract is the water-soluble solution extract of shaggy-fruited dittany.
In a preference, the water-soluble solution extract of described shaggy-fruited dittany is Cortex Dictamni extract.
In a preference, the water-soluble solution extract of described shaggy-fruited dittany is the Cortex Dictamni total alkaloids extract.
In another preference, described water-soluble solution one of is selected from water, methanol aqueous solution, ethanol water, aqueous propanol solution, the butanols aqueous solution or their combination, wherein is preferably the 50-80% ethanol water, most preferably is 70% ethanol water.
In another preference, the water-soluble solution extract of described shaggy-fruited dittany is the Cortex Dictamni alkaloid, it is characterized in that, this Cortex Dictamni alkaloid contains dictamine (dictamnine), γ-.gamma.-fagarine (γ-fagarine), front .beta.-fagarine (preskimmianine), .beta.-fagarine (skimmianine), dasycarpamin (dasycarpamin), trigonelline (trigonelline), choline (choline), O-ethyl-fall-dictamine (O-ethylnordictamnine), (O-ethylnor-γ-fagarine), O-ethyl-fall-.beta.-fagarine (O-ethylnorskimmianine), different speckle boil in the forest-grass alkali (isomaculosidine) one or more to O-ethyl-fall-γ-.gamma.-fagarine.
In another preference, the dosage form of described Halth-care composition is selected from: capsule, tablet, syrup, granule, solution, sweet cream, distillate medicinal water, powder, bright juice, tea-drinking or medicated wine.
In another preference, the dosage form of described cosmetic composition is selected from: liquor, Emulsion, ointment, solid solution ointment, the agent of solid solution clavate, ball lozenge, jelly agent, powder, powder compacting agent, solid formulation or aerosol.
In a fourth aspect of the present invention, provide the purposes of antioxidant of the present invention in preparing prevention or the treatment disease medicament relevant with free radical.
The disease relevant with free radical of the present invention comprises cancer, cardiovascular disease, chronic inflammatory disease, autoimmune disease, gastritis, peptic ulcer, primary glomerulopathy, diabetes, bronchial asthma, emphysema, paralysis agitans, skin aging, aging, skin splash etc.
In a fifth aspect of the present invention, a kind of method for preparing described antioxidant is provided, may further comprise the steps:
A) carry out alcohol extraction with pure comminuted powder to shaggy-fruited dittany;
B) above-mentioned steps ethanol extract a) is carried out decompression and solvent recovery to a small amount of;
C) be dried to driedly, and get final product;
Description of drawings
Fig. 1. Cortex Dictamni extract is on the impact of nematicide survival rate.
The specific embodiment
The inventor is through extensive and deep research, and unexpected the extraction obtains a kind of shaggy-fruited dittany extract, proves further that by cell and zoopery this shaggy-fruited dittany extract has antioxidation, antidotal effect.
Cortex Dictamni extract of the present invention can extract from the root bark of rutaceae shaggy-fruited dittany (Dictamnus dasycarpusTurcz.) and obtain.
Shaggy-fruited dittany of the present invention or Cortex Dictamni extract can prepare by following extraction step:
A) carry out alcohol extraction with pure comminuted powder to shaggy-fruited dittany or Cortex Dictamni;
B) above-mentioned steps ethanol extract a) is carried out decompression and solvent recovery to a small amount of;
C) be dried to driedly, and get final product;
Cortex Dictamni total alkaloids extract of the present invention can prepare by following extraction step:
A) carry out alcohol extraction or sour water lixiviate with pure comminuted powder to Cortex Dictamni;
B) the above-mentioned steps thing liquid of carrying a) is separated by cation exchange resin column or macroporous resin;
C) organic solution eluting;
D) eluent is dried to driedly, and get final product;
Above-mentioned resulting Cortex Dictamni total alkaloids extract is analyzed with HPLC-MS, show that this extract contains dictamine (dictamnine), γ-.gamma.-fagarine γ-fagarine), front .beta.-fagarine (preskimmianine), .beta.-fagarine (skimmianine), dasycarpamin (dasycarpamin), trigonelline (trigonelline), choline (choline), O-ethyl-fall-dictamine (O-ethylnordictamnine), O-ethyl-fall-γ-.gamma.-fagarine (O-ethylnor-γ-fagarine), O-ethyl-fall-.beta.-fagarine (O-ethylnorskimmianine), the different speckle forest-grass alkali (isomaculosidine) that boils.
If necessary, with above-mentioned resulting shaggy-fruited dittany extract or Cortex Dictamni extract or Cortex Dictamni total alkaloids extract, again through subtractive process, just can obtain the higher extract of purity, process for purification for example is to carry out the separation and purification one or many with above-mentioned described column chromatography method respectively again, just can obtain as required more highly purified extract; Or with above-mentioned resulting extract, the solvent with suitable polarity extracts respectively, and extracting solution reclaims to the greatest extent solvent, is concentrated into driedly, after the drying, just can obtain as required more highly purified extract.The solvent of described suitable polarity is selected from the methanol that volume ratio is 75-100: 25-0: water, ethanol: water, acetone: water, or ethyl acetate or chloroform.The extraction solvent that the present invention is used, when being mixed solvent, the ratio between each solvent can be proportioning commonly used in this area, for example the ethanol water of 30%, 60%, 70%, 90% (volume ratio) or methanol-water or acetone water.
Extraction of the present invention can be extracting method conventional in this area, such as reflux, extract,, supersound extraction, ooze rumble extraction, supercritical carbon dioxide extraction etc.
When using water as when extracting solvent, adopt the water extraction of proper sourness, for example hydrochloric acid of pH2～5 or oxalic acid solution can improve the extraction ratio of composition.To those skilled in the art, this is apparent.
The used macroporous resin of the present invention, polyesteramine resin, polydextran gel resin etc. can be respectively resin materials commonly used in this area.For example macroporous resin is D101 type macroporous resin, polydextran gel resin etc.The pretreatment of various resins and Regeneration Treatment etc. all are well known to those of ordinary skill in the art.
Described chromatographic column lock out operation is that the skilled person is known in this area; Described gradient elution, the gradient that determining alcohol changes in the eluant is that the skilled person is easy to determine according to the situation of resin column in this area.During Fractional Collections, can watch the colour band situation of resin column to carry out Fractional Collections by naked eyes, after also can carrying out the equal-volume collection, evaluation by routine is after for example lamellae is identified, contain merging of same composition, also can carry out effluent by the means of the routines such as TLC technique and follow the tracks of discriminating, contain same composition and merge collection etc.This is well-known to one skilled in the art.TLC technique can be referring to " Xu Rensheng " natural product chemistry " Science Press publishes the 589th page of June in 1997." for a person skilled in the art, this is apparent.
Drying of the present invention can be drying means conventional in this area, such as constant pressure and dry, drying under reduced pressure, spray drying or lyophilization etc.
The purposes of material in preparing prevention or the treatment disease medicament relevant with free radical with antioxidation of the present invention.The described disease relevant with free radical includes but not limited to such as cancer, angiopathy, chronic inflammatory disease, autoimmune disease, gastritis, peptic ulcer, primary glomerulopathy, diabetes, bronchial asthma, emphysema, paralysis agitans, aging, skin aging, skin splash etc.
In addition, product of the present invention can be united use to produce cooperative effect with other material.For example, during tumor, product of the present invention can be combined with conventional chemotherapy in treatment, obtain suppress or the kill tumor cell effect in, the oxidative damage that again can ameliorate tumor chemotherapeutics (such as some anthracycline compounds or metal platinum chemical compound etc.) brings.
Usually, when the compounds of this invention is used for such use, they can make with one or more pharmaceutically acceptable carriers or mixed with excipients the pharmaceutical dosage form of different way of administration, such as injection, injectable sterile powder, tablet, capsule, spirit, powder, granule, syrup, solution, tincture, aerosol, powder spray, suppository etc.
But the dosage form of oral administration administration is in the above-mentioned dosage form: tablet, capsule, powder, granule, syrup, solution, spirit.Solid-state carrier comprises: starch, lactose, calcium hydrogen phosphate, microcrystalline Cellulose, sucrose, kaolin, micropowder silica gel, Pulvis Talci, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, polyvinylpyrrolidone.And liquid carrier comprises: sterilized water, ethanol, Polyethylene Glycol, nonionic surfactant and edible oil (such as Semen Maydis oil, Oleum Arachidis hypogaeae semen and Oleum sesami).Normally used adjuvant comprises in the process of pharmaceutical compositions: flavoring agent, coloring agent, antiseptic (such as oxybenzene alkyl butyl ester, sodium benzoate, sorbic acid) and antioxidant (such as vitamin E, vitamin C, sodium pyrosulfite and dibenzylatiooluene).
The dosage form that can be used for injection administration in the above-mentioned dosage form comprises: injection, injectable sterile powder, they are that medicine and one or more pharmaceutically acceptable mixed with excipients are made form for drug administration by injection.Solvent comprises: sterilized water, ethanol, glycerol, propylene glycol, Polyethylene Glycol.In addition, also need add antibacterial (such as benzyl alcohol, butyl hydroxybenzoate, thimerosal), isoosmotic adjusting agent (such as sodium chloride, glucose), suspending agent (such as sodium carboxymethyl cellulose, methylcellulose), solubilizing agent (tween 80, lecithin), antioxidant (such as vitamin E, vitamin C, sodium pyrosulfite) and filler (such as lactose, mannitol).
Can be outside gastrointestinal tract in the above-mentioned dosage form the having of administration: aerosol, powder spray, suppository.The carrier example that is fit in the powder spray comprises: lactose, glucosan, arabic gum, manna, glucose and sodium lauryl sulphate.The solvent that is fit in the aerosol is sterilized water, ethanol, vegetable oil, oleic acid.The propellant that is fit to is isceon, dichlorodifluoromethane, propane, iso-butane, carbon dioxide, nitrogen.The preparation of suppository can mix medicine and a kind of suitable nonirritant excipient, and excipient comprises: cocoa butter, PEG-4000, PEG-4000, ethyl hydroxybenzoate, glycerol.
From being easy to prepare the position with administration, preferred pharmaceutical composition is solid-state composition, especially the capsule of tablet and solid-filling or liquid filling.The preferred oral administration.
The effective dose of used active component can change with the order of severity of mode of administration and disease to be treated.Yet, usually when chemical compound of the present invention every day gives with the dosage of about 0.5-500mg/kg the weight of animals, can obtain gratifying effect, preferably give with the dosage that separates for 2-4 time every day, or with the slow release form administration.For most of large mammal, the accumulated dose of every day is about 1-100mg.The dosage form that is applicable to take orally comprises the reactive compound of the about 0.5-500mg that mixes with solid-state or liquid pharmaceutically acceptable carrier.This therapeutic scheme of scalable is to reach optimum therapeuticing effect.For example, can be according to the needs for the treatment of situation, every day, several times separated administration, or dosage is reduced in proportion.Usually, becoming the scope of human oral clinical dosage is 1-1000mg/ day, is preferably 10-200mg/ day, and the non-oral dosage of being grown up is 0.1-100mg/ day, preferred 1-100mg/ day.
When using extract antioxidation of the present invention, also can with other treatment agent coupling.For example with one or more auxiliary activity composition couplings that are selected from lower group: vitamin C, vitamin E, coenzyme Q10, Thioctacid, Glutathione Dependent (GSH-Px), superoxide dismutase (SOD), procyanidin.
The present invention also provides cosmetic composition, it is used for antioxidation, skin aging suppresses, promotes skin elasticity or improve wrinkle, it contains extract of the present invention or by isolating one or more chemical compounds of selecting in the chemical compound in the said extracted thing, selected chemical compound is as the effective ingredient of compositions.
Extract of the present invention or the active component that separates from this extract have the excellent antioxidant activity such as peroxidation suppresses active and removing free radical activity; therefore it can effectively be used as cosmetic composition; said composition has the skin aging of inhibition, improves skin elasticity or wrinkle-care effect, and this is because the cause that said composition can be protected skin and prolong cell survival.
Cosmetic composition of the present invention can as the raw material of basic skin nursing, such as soft lotion, nutrition lotion, nutritional emulsifiable paste agent, essence, facial film or bath powder, perhaps can be used as the external preparation of skin.
Extract of the present invention can be made multiple cosmetic formulations, such as the multiple emulsion of solution, anhydrous formulation, aerosol, emulsion, water in oil microemulsion or oil-in-water type, gel, solid bar, ointment etc.In addition, the adjuvant that can also contain other cosmetic formulations, such as the conventional ingredient in antiseptic, antibacterial, spice, antifoaming agent, dyestuff, pigment, thickening agent, surfactant, emulsifying agent, softening agent, water-repellent agent, wetting agent, fat, oil, wax or other cosmetics, such as alcohol, polyhydric alcohol, polymer, foam stabiliser, electrolyte, organic solvent or silicone derivative etc.
During the preparation cosmetic composition, after considering emulsification and business efficiency, will determine the content of oil component.As oil component, can use one or more oil of from the group that is formed by vegetable oil, mineral oil, silicone oil and artificial oil, selecting.In addition, in order to improve emulsification, can add surfactant and the higher alcohol of 0.1～5 % by weight.Can utilize common surfactant such as non-ionic surface active agent, and as for higher alcohol, can use separately the alcohol with 12～20 carbon numbers, perhaps should mix use with the alcohol of other kind by alcohol.
Be the preparation cosmetic composition, can add in the aqueous components with adjusting viscosity or solidify with at least a in will the thickening agent such as carbomer (carbomer), bentonite, xanthan gum etc. of 0.00l～5 % by weight.
For preparing cosmetic composition of the present invention, also can increase medicine such as higher fatty acids, vitamin etc. and other common additives that is used for cosmetics such as UV protective agent, antioxidant, antiseptic, spice, coloring agent, pH value regulator etc.
In a preferred embodiment of the invention, the described extract of the application of the invention can prepare soft lotion, viscous solution, emulsus lotion and ointment.In order to prepare the cosmetic composition that contains extract of the present invention, in common compositions, add in addition the extract of 1～10 % by weight, more preferably add 2～10 % by weight.
When using extract of the present invention to prepare antioxidation, anti-aging cosmetics, can also with one or more antioxidant couplings that are selected from lower group: VitAVitE, cysteine, ascorbic acid, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), metallothionein, Fructus Chaenomelis sulfydryl enzyme, ubiquinone
10
Said among the present invention " health food " refers to have the food of specific health care, namely is applicable to specific crowd and eats, has and regulate body function, the direct food take treatment as purpose not.This health food contains the extract of the present invention of l～50% (weight) usually.
Functional food of the present invention, refer to contain the similar food products such as food, beverage or milk product of extract of the present invention, effective site can be added in the food with adding, mixing, coating, combination or other approach and go, or to dissolve, to suspend or to be suspended in beverage, the milk product.The food, beverage or the milk product that contain extract of the present invention can the establishing criteria method easily prepare.
Major advantage of the present invention is:
The invention provides a kind of polyphenoils that from shaggy-fruited dittany, extracts, has good antioxidation, stable preparation process, quality standard is controlled, good stability, have no side effect, can use it in preparation antioxidative medicine, health food or the cosmetics, have the advantages such as evident in efficacy, cheap, easy to use.
Below in conjunction with specific embodiment, further set forth the present invention.These embodiment only are not used in for explanation the present invention and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, or the condition of advising according to manufacturer.
The preparation of embodiment 1 extract
The preparation of Cortex Dictamni extract
With 50L 70% ethanol the comminuted powder of 5Kg Cortex Dictamni is carried out alcohol extraction; Above-mentioned ethanol extract is carried out decompression and solvent recovery to a small amount of; Drying under reduced pressure namely gets Cortex Dictamni extract APD-002 to doing;
The preparation of Cortex Dictamni total alkaloids extract
With 50L pH2.0 aqueous hydrochloric acid solution the comminuted powder of 5Kg Cortex Dictamni is carried out the sour water lixiviate; Then the above-mentioned thing liquid of carrying is passed through cation exchange resin column; To adsorb alkaloidal cationic resin and be washed till neutrality; Adopt 50% ethanol and acetone eluting isolating alkaloids; Eluent is dried to dried, namely gets Cortex Dictamni total alkaloids APD-N2;
The alkaloid compound qualitative experiment: the Cortex Dictamni total alkaloids that takes a morsel is dissolved in 95% methanol solution, get 20 μ l points on silica gel g thin-layer plate, under developing solvent chloroform-methanol (8: 1) condition, launch, with alkaloid developer-bismuth potassium iodide colour developing, be brownish red.
Embodiment 2 extracts are on beautiful nematicide (C.elegans) impact in existence life-span
Experiment material:
C.elegans (DH2) plants, available from Institute of Molecular and Cell BiologyNational University of Singapore; The SOD quantitative determination reagent kit builds up bio-engineering corporation available from Nanjing; Resveratrol is available from the Shanghai monarch thing Science and Technology Ltd. that creates; Trizol Reagent is available from U.S. Gibcol company; Cortex Dictamni extract APD-002, Cortex Dictamni total alkaloids APD-N2 is prepared by EXAMPLE l.
Experimental technique: reference literature (Dillin A.et.al.Science, 2002,298:830-834.BartP.et.al Mechanisms of ageing and Development, 2002,123:105-119) method is measured APD-002, APD-N2 C.elegans is given birth to long-life impact.At first process adult with 50% liquor natrii hypochloritis and 1M potassium hydroxide solution, collect egg cultivation in S-medium, treat that Adult Development is to the L1 after date, it is counted picking to culture plate by respective sample, when polypide grows to L4 during the phase, add the 5-FUD of 50 μ M to suppress the adult breeding, add simultaneously corresponding medicine.
1. survival Analysis: observe the survival number of C.elegans every day, until till the whole death of polypide, with life table method and Gehan ' s Wilcoxon existence life-span of each group relatively, the results are shown in Table 1.
2. the mensuration of superoxide dismutase (SOD) content: add 5-FUD and relative medicine two days later, centrifugal acquisition polypide, extract albumen with Trizol Reagent, measure SOD content by measuring the test kit description, test kit builds up bio-engineering corporation by Nanjing and produces.Respectively organize mean with the t check, the results are shown in Table 2.
Experimental result:
Shown in table 1, table 2, Cortex Dictamni extract, Cortex Dictamni total alkaloids and resveratrol all can prolong the average life of C.elegans, improve the level of SOD, Cortex Dictamni extract is compared with resveratrol with the Cortex Dictamni total alkaloids, its life-saving and antioxidant effect are more remarkable, and both have compared significant difference (p＜0.05).
Table 1 Cortex Dictamni extract is on the C.elegans impact (X ± SD, n=90) in existence life-span
| Group | Average life (my god) |
| Matched group | 14±3.1 |
| Resveratrol group (10 μ M) | 18±5.2 * |
| APD-002 organizes (50 μ M) | 23±5.8 **△ |
| APD-N2 organizes (50 μ M) | 25±2.0 **△ |
" * " represents p＜0.05, compares with matched group to have significant difference;
" * * " represents p＜0.01, compares with matched group to have utmost point significant difference;
" △ " represents p＜0.05, compares with the resveratrol group to have significant difference.
Table 2 Cortex Dictamni extract is on the impact (X ± SD, n=90) of nematicide SOD expression
| Group | SOD content (U/ml) |
| Matched group | 25.3±1.66 |
| Resveratrol group (10 μ M) | 37.7±8.15 * |
| APD-002 organizes (50 μ M) | 53.1±13.26 **△ |
| APD-N2 organizes (50 μ M) | 60.3±7.25 **△ |
" * " represents p＜0.05, compares with matched group to have significant difference;
" * * " represents p＜0.01, compares with matched group to have utmost point significant difference;
" △ " represents p＜0.05, compares with the resveratrol group to have significant difference.
Embodiment 3 Cortex Dictamni extracts cause the protective effect of subacute aging model mice to the D-galactose
Laboratory animal: male SPF level kunming mice, available from Shanghai Slac Experimental Animal Co., Ltd., body weight is 18-22g, and SPF level Animal House is raised, and 12h illumination/12h is dark, freely absorbs feedstuff and water.
Experiment material: resveratrol, available from the Shanghai monarch thing Science and Technology Ltd. that creates; Cortex Dictamni extract APD-002 is prepared by embodiment 1; The D-galactose is available from Shanghai biochemical reagents two factories; SOD, MDA quantitative determination reagent kit all build up bio-engineering corporation available from Nanjing.
Experimental technique: mice is divided into respectively 5 groups at random, 10 every group: (1) matched group gives normal saline; (2) model group gives the D-galactose, and dosage is 80mg/kg; (3) medication A group, giving dosage is the D-galactose of 80mg/kg, gives simultaneously the resveratrol that dosage is 20mg/kg; (4) medication B group, giving dosage is the D-galactose of 80mg/kg, giving simultaneously dosage is the Cortex Dictamni extract APD-002 of 100mg/kg.More than each group be intraperitoneal injection, every day 1 time, totally 6 weeks, experiment finishes to put to death animal.By measuring the operation of test kit description, survey malonaldehyde (MDA) content in mouse core, liver, the cerebral tissue, reach superoxide dismutase (SOD) content in very thin born of the same parents, liver, the cerebral tissue.
The result: experimental result sees Table 3, table 4, and Cortex Dictamni extract and resveratrol phase specific energy significantly reduce the content of lipid peroxidation product MDA in the tissue, improves the content of superoxide dismutase (SOD), and it has antioxidation and antidotal effect.
Table 3 Cortex Dictamni extract is on the impact (X ± SD, n=10) of MDA content
" * " represents p＜0.05, compares with matched group to have significant difference;
" * * " represents p＜0.01, compares with matched group to have utmost point significant difference;
" △ " represents p＜0.05, compares with medication A group to have significant difference.
Table 4 Cortex Dictamni extract is on the impact (X ± SD, n=10) of SOD content
" * " represents p＜0.05, compares with matched group to have significant difference;
" * * " represents p＜0.01, compares with matched group to have utmost point significant difference;
" △ " represents p＜0.05, compares with medication A group to have significant difference.
Can find out that from above-mentioned effect embodiment Cortex Dictamni extract has good antioxidation and/or defying age effect; Compare with resveratrol, its antioxidant effect greatly improves (p＜0.05).
The experiment of embodiment 4 nematicide N,N'-dimethyl-.gamma..gamma.'-dipyridyliums
Experiment material:
C.elegans (DH2) plants, available from Institute of Molecular and Cell BiologyNational University of Singapore; The SOD test kit builds up bio-engineering corporation available from Nanjing; Resveratrol is available from the Shanghai monarch thing Science and Technology Ltd. that creates; N,N'-dimethyl-.gamma..gamma.'-dipyridylium is available from the safe pesticide chemical company limited of Anhui gold; Cortex Dictamni extract APD-002 is prepared by embodiment 1.
Experimental technique:
1. cultivate nematicide in ware;
2. experiment is divided into 2 groups: the APD-002 group, add the APD-002 that DMSO dilutes, every hole 100 μ l, final concentration is respectively 10,30,90,270,810 μ M; The resveratrol group adds the resveratrol that DMSO dilutes, every hole 100 μ l, and final concentration is respectively 10,30,90,270,810 μ M.More than each group, establish 3 multiple holes for every group.
3. from culture dish in nematicide to 96 orifice plate of picking L4,10 in every hole.After 48 hours, every hole adds with the Pennisetum centrasiaticum Tzvel of DMSO dilution withered, every hole l0 μ l, and final concentration is 400 μ M.Act on after 48 hours, record nematicide survival condition is calculated survival rate, then calculates the corresponding logarithm value of survival rate.
Experimental result:
As shown in Figure 1, Cortex Dictamni extract possesses the activity of antioxidant radical, can significantly improve the survival rate of nematicide, has the effect that prolongs the nematicide life-span, and successful is better than resveratrol, and has significant difference (p＜0.05).
The preparation of embodiment 5 tablets
Utilize routine techniques, mix following component, direct compression then, the pharmaceutical composition of preparation tablet form, its prescription is as follows:
| Composition | Recipe quantity (g/1000 sheet) |
| The APD-002 that embodiment 1 makes | 100 |
| Lactose | 50 |
| Microcrystalline Cellulose | 40 |
| Corn starch | 6 |
| Carboxymethyl starch sodium | 3 |
| Magnesium stearate | 1 |
| |
200 |
The preparation of embodiment 6 injections
| Composition | Recipe quantity (g/1000ml) |
| The APD-002 that embodiment 1 makes | 10 |
| Sodium sulfite | 0.2 |
| Sodium carboxymethyl cellulose | 5 |
| Tween 80 | 1.5 |
| Water for injection | Add to 1000ml |
1. sodium sulfite is added in the 500ml water for injection, adds sodium carboxymethyl cellulose, mixing, soaked overnight (24 hours), complete molten after, filter with 210 order nylon cloths;
2. with 1. heating in water bath of solution, add tween 80, mixing;
3. to the water-bath boiling, add the APD-002 that embodiment 1 makes, mixing continues heating 30 minutes, takes out and is cooled to room temperature, and the G3 sintered glass funnel filters;
4. inject water to 1000ml, mixing, embedding is with 100 ℃ of sterilizations in 30 minutes.
Embodiment 7 preparations contain the functional food of extract
1. preparation contains the food of Cortex Dictamni extract
The APD-002 that the embodiment 1 of capacity is made joins in the wheat flour, makes the wheat flour mixture that every 100g contains the about 5g of Cortex Dictamni extract.Adopt this wheat flour mixture to prepare bread, cake, cookies, crispbread, noodles, instant noodles etc., thereby obtain to contain the functional food of Cortex Dictamni extract active component.
2. preparation contains the milk product of Cortex Dictamni extract
The Cortex Dictamni extract APD-002 that the embodiment 1 of capacity is made joins in the milk, makes the mixed milk that contains the about 2-5g of Cortex Dictamni extract in every 100g milk, then prepares various milk product by it, such as yoghourt, icecream, cheese etc.
3. preparation contains the beverage of Cortex Dictamni total alkaloids extract
The Cortex Dictamni total alkaloids extract APD-N2 that the embodiment 1 of capacity is made joins in vegetable juice, fruit juice or the soda pop, obtain to comprise in every 100ml beverage the Cortex Dictamni total alkaloids extract of 0.1-10g, thereby obtain containing the functional food of Cortex Dictamni total alkaloids extract active component.
Embodiment 8 preparations contain the cosmetic Emulsion of skin care item of Cortex Dictamni extract
Cortex Dictamni extract APD-002 with 5g, Tween 60,1g anhydrosorbitol monostearate, 10g mineral oil, 5g three caprylates, 0.5g triethanolamine, 5g glycerol, 3g propylene glycol, an amount of antiseptic, an amount of spice and surplus pure water with 1g stearic acid, 2g spermol, 1g, mix, make the Emulsion that prevents skin aging, facial colour spot or freckle of 100g.
All quote in this application as a reference at all documents that the present invention mentions, just as each piece document is quoted separately as a reference.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims limited range equally.
Claims (7)
1. the antioxidant purposes in preparation prevention or treatment antioxidation and antiaging agent; Wherein this antioxidant contains the water-soluble solution extract of shaggy-fruited dittany, and described water-soluble solution extract is the Cortex Dictamni total alkaloids extract.
2. purposes according to claim 1 is characterized in that described water-soluble solution one of is selected from water, methanol aqueous solution, ethanol water, aqueous propanol solution, the butanols aqueous solution or their combination.
3. purposes according to claim 1 is characterized in that described water-soluble solution is the 50-80% ethanol water.
4. purposes according to claim 1 is characterized in that described water-soluble solution is 70% ethanol water.
5. purposes according to claim 1, it is characterized in that described antioxidant contains dictamine, γ-.gamma.-fagarine, front .beta.-fagarine .beta.-fagarine, dasycarpamin, trigonelline, choline, O-ethyl-fall-dictamine, O-ethyl-fall-γ-.gamma.-fagarine, O-ethyl-fall-.beta.-fagarine and the different speckle forest-grass alkali that boils.
6. purposes according to claim 1 is characterized in that, described medicine is:
(a) active component of described antioxidant: 1-99% weight portion;
(b) pharmaceutically acceptable carrier.
7. pharmaceutical composition according to claim 6 is characterized in that the dosage form of described medicine is selected from: injection, injectable sterile powder, tablet, capsule, spirit, powder, granule, syrup, solution, tincture, aerosol, powder spray or suppository.
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| CN102114104A (en) * | 2010-01-06 | 2011-07-06 | 中国医学科学院药用植物研究所 | New application of dittany bark extract in resisting atherosclerosis |
| CN102648941A (en) * | 2011-02-28 | 2012-08-29 | 中国医学科学院药用植物研究所 | New application for antioxidation action of cortex dictamni extract |
| CN105249439A (en) * | 2015-11-10 | 2016-01-20 | 朱丽芬 | Sticky powdered sugar having antioxidant function |
| CN106539093A (en) * | 2017-01-13 | 2017-03-29 | 王卫东 | A kind of gene repair fully nutrient |
| CN108186635A (en) * | 2018-03-29 | 2018-06-22 | 上海壹志医药科技有限公司 | The new pharmaceutical uses of dictamine |
| CN108354937A (en) * | 2018-03-29 | 2018-08-03 | 上海壹志医药科技有限公司 | The new pharmaceutical uses of fagarine |
| CN109602621A (en) * | 2018-12-25 | 2019-04-12 | 珠海中科先进技术研究院有限公司 | A kind of skin care item and preparation method thereof containing choline gallate |
| CN109528532A (en) * | 2018-12-25 | 2019-03-29 | 珠海中科先进技术研究院有限公司 | A kind of skin care item and preparation method thereof containing choline vanillate |
| CN109602626A (en) * | 2018-12-25 | 2019-04-12 | 珠海中科先进技术研究院有限公司 | A kind of skin care item and preparation method thereof containing choline salicylate |
| CN109528536A (en) * | 2018-12-25 | 2019-03-29 | 珠海中科先进技术研究院有限公司 | A kind of skin care item and preparation method thereof containing choline ellagic acid salt |
| CN109528533A (en) * | 2018-12-25 | 2019-03-29 | 珠海中科先进技术研究院有限公司 | A kind of cosmetics and preparation method thereof containing choline cloves hydrochlorate |
| CN109528611A (en) * | 2018-12-25 | 2019-03-29 | 珠海中科先进技术研究院有限公司 | A kind of skin care item and preparation method thereof containing choline caffeiate |
| CN110882248B (en) * | 2019-12-31 | 2020-12-22 | 中南民族大学 | Application of dictamnine in preparation of medicine for relaxing pre-contracted tracheal smooth muscle |
| CN111264569B (en) * | 2020-04-08 | 2021-05-04 | 哈尔滨职业技术学院 | Combined extraction and separation method of total volatile oil and total alkaloids in cortex dictamni, preparation thereof and application of preparation in preventing and treating rice blast |
| CN114246868B (en) * | 2021-12-24 | 2023-06-06 | 中国人民解放军军事科学院军事医学研究院 | Inhibitor of urinary tract infection pathogen urinary tract pathogenic escherichia coli |
| CN117551625B (en) * | 2024-01-12 | 2024-03-08 | 山东爱维德生物科技有限公司 | Polyethylene glycol diamine-alginic acid modified SOD enzyme for arborescent aloe SOD gel and application thereof |
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