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CN100361599C - Antioxidative compositions - Google Patents

Antioxidative compositions Download PDF

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Publication number
CN100361599C
CN100361599C CNB2003801021043A CN200380102104A CN100361599C CN 100361599 C CN100361599 C CN 100361599C CN B2003801021043 A CNB2003801021043 A CN B2003801021043A CN 200380102104 A CN200380102104 A CN 200380102104A CN 100361599 C CN100361599 C CN 100361599C
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CN
China
Prior art keywords
composition
vitamin
quercetin
tea
epicatechin
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Expired - Fee Related
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CNB2003801021043A
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Chinese (zh)
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CN1708234A (en
Inventor
托马斯·克里斯琴·莱恩斯
小野光则
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FRS Co.
The new nutrition Co.
The new nutrition LLC
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Quercegen Holdings LLC
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
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    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/02—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation containing fruit or vegetable juices
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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Abstract

This invention relates to a composition that contains quercetin, vitamin B1, viamin B2, vitamin B3, vitamin B6, vitamin C, caffeine, epigallocatechin gallate, epicatechin, epicatechin gallate, epigallocatechin, and polypheron E.

Description

Antioxidant composition
The cross reference of related application
The application requires in the priority of the 10/302nd, No. 544 U.S. Patent application of submission on November 22nd, 2002, and it requires again in the 60/420th, No. 986 U.S. Provisional Application No. of submission on October 23rd, 2002.
Technical field
The present invention relates to antioxidant composition.
Background technology
As everyone knows, some natural such as plant flavonoids can suppress the acute or chronic disease of free-radical induced.And there is synergy (synergy) in some natural when reacting with the oxide relevant with biology such as hydroxyl, peroxide, oxysulfide (oxysulfurs), sulfur dioxide and nitrogen dioxide.For example, the collaborative antioxidation activity of vitamin C and phenol antioxidant has been found in research.
Summary of the invention
The present invention is based on a beat all discovery, Quercetin, a kind of antioxidant, and multiple other natural products has collaborative wholesome effect.
The present invention discloses a kind of composition, and it comprises following ingredients: vitamin B1, vitamin B2, vitamin B3, vitamin B6, cobalamin, vitamin C, caffeine, Quercetin, Epigallo-catechin gallate (EGCG), epicatechin, L-Epicatechin gallate, epigallocatechin and remove caffeinum green tea catechin mixture (polyphenon E).Said composition also can comprise other composition, as vitamin E, CoQ-10, isoflavones, taurine, beet pectin fiber or ginkgo biloba extract.Said composition also can further optionally be added sweetener to improve sugariness, and aforementioned sweetener is for example sorbierite, maltitol, sucrose, high-fructose corn syrup etc.Said composition also can comprise amino acid, mineral matter, flavoring agent or colouring agent.The leaf of green tea is known to be comprised Epigallo-catechin gallate (EGCG), epicatechin, L-Epicatechin gallate, epigallocatechin and removes caffeinum green tea catechin mixture.Therefore aforementioned five kinds of compositions are fit to be provided by green-tea extract.
The present composition can be dried forms (as powder or tablet) or moisture form (as beverage or syrup).It can be dietary supplement or pharmaceutical preparation, also can be beverage or food.The example comprises: tea (as tea beverage or tea bag content), soft drink, fruit juice (as fruit extract or fruit drink), milk, coffee, biscuit, cereal based food (cereals), chocolate and snack food (snack bars).The present composition all can be used for treatment of arthritis, tumour, sex dysfunction, chronic constipation, inflammatory bowel disease under any aforementioned forms; Improve notice or mood; And reduction cholesterol levels or blood pressure.Also belong within the scope of the present invention in the application that preparation is used for the treatment of in the medicine of above-mentioned disease as the present composition of active medicine and said composition.
Along with hereinafter narration provides one or more specific embodiment of the present invention.Other features of the present invention, purpose and advantage will be illustrated by specification and claims.
The specific embodiment
The present composition comprises vitamin B1, vitamin B2, vitamin B3, vitamin B6, cobalamin, vitamin C, caffeine, Quercetin, Epigallo-catechin gallate (EGCG), epicatechin, L-Epicatechin gallate, epigallocatechin and removes caffeinum green tea catechin mixture.Green-tea extract is suitable for providing Epigallo-catechin gallate (EGCG), epicatechin, L-Epicatechin gallate, epigallocatechin and removes caffeinum green tea catechin mixture.
The exemplary-amounts of said composition composition is: the 0.1-50mg vitamin B1,0.1-150mg vitamin B2,0.1-2000mg vitamin B3,0.1-200mg vitamin B6,5-150 μ g cobalamin, the 50-2000mg vitamin C, the 50-1500mg caffeine, the 20-2000mg Quercetin, the 10-500mg Epigallo-catechin gallate (EGCG), the 10-500mg epicatechin, the 10-500mg L-Epicatechin gallate, 10-500mg epigallocatechin and 10-500mg remove caffeinum green tea catechin mixture, wherein aforementioned composition solubilized or be scattered in the 1L aqueous solution.It is identical with the relative scale of aforementioned content that the content of these compositions also can be.Term " Quercetin " refer to quercetin aglycon and quercetin derivative, for example: Quercetin-3-O-glucoside, Quercetin-5-O-glucoside, Quercetin-7-O-glucoside, Quercetin-9-O-glucoside, Quercetin-3-O-rutinoside, Quercetin-3-O-[α-rhamanopyranosyl-(1 → 2)-α-rhamanopyranosyl-(1 → 6)]-β-glucoside, Quercetin-3-O-galactoside, Quercetin-7-O-galactoside, Quercetin-3-O-rhamnoside and Quercetin-7-O-rhamnoside.After digestion, quercetin derivative is converted into quercetin aglycon, a kind of activity form that is absorbed by health.Aforementioned quercetin content refers to the content of Quercetin part in quercetin aglycon or the quercetin derivative.For example: the composition that use every day can be the 1L aqueous solution, and this aqueous solution comprises 1000mg Quercetin, 30mg vitamin B1,85mg vitamin B2,1g vitamin B3,100mg vitamin B6,120 μ g cobalamins, 1200mg vitamin C, 1000 IU vitamin Es, 1000mg caffeine and comprises the green-tea extract that 120mg Epigallo-catechin gallate (EGCG), 140mg epicatechin, 360mg L-Epicatechin gallate, 360mg epigallocatechin and 120mg remove caffeinum green tea catechin mixture.
Said composition also can comprise one or more other active components, as vitamin E, CoQ-10, isoflavones, taurine, beet pectin fiber and ginkgo biloba extract.The exemplary-amounts of these compositions is: the CoQ-10 of 3-1000 IU vitamin E, 10-400mg, 20-600mg isoflavones, 10-1000mg taurine, 1-15g beet pectin fiber and 50-500mg ginkgo biloba extract (dry weight).Said composition also can further optionally improve sugariness by adding sweetener, and sweetener for example is sorbierite, maltitol, hydrogenated glucose syrups, hydrogenated starch hydrolysates, high-fructose corn syrup, sucrose, beet sugar, pectin and sucralose.
An example of foregoing is a powder type, and it is applicable to the preparation beverage, as tea or fruit juice.This powder composition also can be used for preparing paste, gel, capsule or tablet.Lactose and cornstarch are used as dilution usually and are used as carrier in tablets in capsule.Generally can add lubricant, as dolomol, to form tablet.
The present composition can be dietary supplement or pharmaceutical preparation.As dietary supplement, said composition can comprise extra nutrients such as mineral matter or amino acid.Said composition also can be beverage or food, as tea, soft drink, fruit juice, milk, coffee, biscuit, cereal based food, chocolate and snack food.
The present composition all can be used for treating disease or illness under any aforementioned forms, as arthritis, tumour, sex dysfunction, chronic constipation, inflammatory bowel disease; And improve notice or mood; And reduction cholesterol levels or blood pressure.Term " tumour " refers to benign tumour and malignant tumour (leukaemia, colon cancer, kidney, liver cancer, breast cancer or lung cancer).Term " treatment ", " improvement " reach " reduction " and point to the patient who suffers from one or both aforementioned diseases or illness, or has a present composition of patient's effective dosage of the symptom of one or more aforementioned diseases or tendency, its purpose is to cure, alleviate, alleviate, correct or improve one or more diseases or illness, or the symptom of one or more diseases or illness or tendency.Term " administration " contains that oral or parenteral route transmits the present composition to the patient with any suitable form, and this suitable form is for example food, beverage, tablet, capsule, supensoid agent and solution.That term " parenteral route " refers to is subcutaneous, in the intracutaneous, intravenous, intramuscular, joint, in the artery, in the synovia, in the breastbone, in the sheath, in the focus or injection in the skull, and different infusion techniques.Term " effective dose " refers to fully to provide the composition dosage of treatment curative effect, and this curative effect is for for example reducing cholesterol levels or blood pressure.Can carry out reaching in the body in vitro test to determine best method of administration and dosage.
Following specific embodiment should be considered to only be illustrative, and must not be considered to be used to limit other parts disclosed in this invention.Any disclosed content of personage Ke Yiben specification of being familiar with the present technique field does not need further to set forth and can utilize the present invention fullest.All documents cited herein are incorporated herein by reference in full at this.
Preparation 1 is prepared as follows.Under the room temperature, in the 30mL pure water, add vitamin B1 (8mg), vitamin B2 (21.1mg), vitamin B3 (248mg), vitamin B6 (24.8mg), cobalamin (20.4mg), vitamin C (74.4mg), vitamin E (37.2 IU), caffeine (99.2mg), quercetin aglycon (248mg) and comprise Epigallo-catechin gallate (EGCG) (80mg), epicatechin (80mg), L-Epicatechin gallate (80mg), epigallocatechin (80mg) and remove the green-tea extract of caffeinum green tea catechin mixture (80mg).All the components can be from Spectrum Laboratory Products, Inc., Gardena, CA; Sigma, St.Louis, MO; And Aldrich, Milwaukee, WI. obtains.Aforementioned mixture is puddled the device vigorous stirring with food, be diluted to 150mL with pure water then.
In an experiment, male Spregue-dawley rat (150-180 gram, Charles RiverLab, boston, MA) but be placed in the top cage of filter screen and ad lib food and water arranged, and support in duration of test inner control temperature and photoperiodic malleation room.The animal model of inflammatory bowel disease (as Crohn ' s disease), colitis (colon growth that inflammation causes) is dissolved in the 25mg hapten reagent 2 of 0.5ml volume ratio 30% ethanol by instiling in colon, (TCI Japan) induces the 4-dinitrobenzene sulfonic acid.Each rat with metafane anesthesia, is injected in the colon DNBS/ ethanol apart from 8 centimeters places of anus with PE 50 intubate earlier then.Slowly inject the 2ml air by intubate then and stay colon, afterwards rat is kept stand up position and put back in the mouse cage after 30 seconds to guarantee solution.With identical method, for blank group rat is injected 0.5ml, 30% ethanol.See also Hogaboam, etc., Eur.J.Pharmacol. (1996) 309:261-269.Preparation 1 and comprise methylcellulose (MC) ultimate density be 1% quercetin aglycon solution respectively once a day oral way raise and give rat, continue 7 days.Each, dosage comprised the quercetin aglycon of per kilogram of body weight 3.125mg to 25mg every day.The body weight of per 24 hours monitoring rats.At the 7th day, the execution rat was also taken out colon and weighs.Before taking out each bar colon, whether record colon and other organ exist adhesion when opening the abdominal cavity, calculate colon-weight ratio of every animal then, the excipient control group is with respect to the net increase conduct and treatment group a reference value relatively of blank group ratio.Preparation 1 can suppress colon with quercetin aglycon under 25mg/kg dosage grows up, and grows up but can't suppress colon under the dosage of 3.125mg/kg.Yet under the dosage of 6.25mg/kg and 12.5mg/kg, the inhibition of 1 pair of colon growth of preparation is effective more than quercetin aglycon.
In another experiment, prepare the bacterial suspension of 10mg/ml, heat-killed tubercle bacillus H37Ra in incomplete Freund's adjuvant by soil floating.In female Lewis rat with the aforementioned supensoid agent intracutaneous injection of 0.1ml to the tail base portion to bring out adjuvant-induced arthritis (AA).Then, that day after the self-induction, this rat preparation 1 of orally give or quercetin aglycon solution (1%MC) continue 12 days once a day, and every day, dosage was the 25mg/kg quercetin glycoside.Between the key period (from back 10 to 25 of immunity), the development of the monitoring polyarthirtis that detects by an unaided eye every day also is all animals appointment arthritis index.The intensity of polyarthirtis is according to the scoring of following scheme: (a) according to the scoring that to give every claw grade be 0-3 of erythema, swelling and the deformity in joint, i.e. 0 expression does not have erythema or swelling; If at least one joint, can be observed swelling then give 0.5; Slight swelling and the erythema of 1 expression; 2 expression ankles and carpal bone all have swelling and erythema; 3 expression arthrocleisis and bone deformities.(b) grade of health other parts: 0.5 expression ear takes on a red color, and another 0.5 expression ear has lump; 1 expression nose connective tissue swelling; Reach 1 knotting of expression tail or kink.With reference to Schorlemmer etc., Drugs Exptl.Clin.Res. (1991) 17:471-483.With the rat of using the quercetin aglycon treatment relatively, demonstrate more significantly with the rat of preparation 1 treatment arthritic symptom 18 days the time and to improve.
In another experiment, female BD2F1 (C57BL/6xDBA/2F1) rat obtains from CharlesRiver Lab.But rat ad lib food and water.At the 0th day, inoculate 50,000 p388 leukaemias as animal model for cancer in the female BD2F1 rat peritoneum to 7 ages in week.Preparation 1 or quercetin aglycon solution (1%MC) oral administration continue 14 days once a day, and every day, dosage was the 12.5mg/kg quercetin aglycon.All control rats but not treatment group rat dies from ascites when 21 days left and right sides.Mean survival time by relatively treatment group and control group is determined active anticancer.With reference to Yoshimatsu etc., cancer Res. (1997) 57:3208-3213.Compare with the rat for the treatment of with quercetin aglycon, with the much longer mean survival time of rat demonstration of preparation 1 treatment.
Phosphodiesterase-5 (PDE-5) is a kind of enzyme of property of participation function.In further testing, measure the activity of PDE-5 with the well-known method of correct.With reference to Thompson etc., Method Enzymol. (1974) 38:205-212.The activity of purifying PDE-5 is by preparation 1, quercetin aglycon solution and the 3-isobutyl-1-methylxanthine (IBMX of variable concentrations in 1 μ M to 100 μ M scope, a kind of common PDE-5 inhibitor) solution (1%MC) exists down and the mixture response measurement of pH 7.5, this mixture comprise 8 μ M cGMP (64 μ Ci/ml [ 3H]-cGMP), 40mM MOPS, 0.5mM EGTA, 15mM magnesium acetate, 0.15mg/mlBSA.This is reflected at and carried out under 37 ℃ 60 minutes, is heated to 70 ℃ then and keeps 2 minutes with cessation reaction.Afterwards, the enzymatic reaction product of mark [ 3H]-GMP in the presence of the nucleotidase of 0.1 unit, be degraded into [ 3H]-guanosine and phosphoric acid.At last, undegradable [ 3H]-cGMP is adsorbed in anion exchange resin, in the supernatant [ 3H]-guanosine counts in liquid scintillation counter and measures its radioactivity.The result shows that the capability list that preparation 1 suppresses the PDE-5 activity reveals dose dependent, and its IC50 value is far below quercetin aglycon and IBMX.
Also carried out the human research to estimate the present invention other two kinds of preparations, i.e. preparation 2 and 3.Preparation 2 is prepared as follows.Under the room temperature, in the 200mL pure water, add vitamin B1 (30mg), vitamin B2 (85mg), vitamin B3 (1g), vitamin B6 (100mg), cobalamin (120 μ g), vitamin C (1200mg), vitamin E (1000 IU), caffeine (1000mg), quercetin aglycon (1000mg) and comprise Epigallo-catechin gallate (EGCG) (120mg), epicatechin (140mg), L-Epicatechin gallate (360mg), epigallocatechin (360mg) and remove the green-tea extract of caffeinum green tea catechin mixture (120mg).Puddle the aforementioned mixture of device vigorous stirring with food, be diluted to 1L with pure water then.Being prepared as follows of preparation 3.Under the room temperature, in the pure water of 200mL, add vitamin B1 (3.75mg), vitamin B2 (4.25mg), vitamin B3 (50mg), vitamin B6 (5mg), cobalamin (15 μ g), vitamin C (150mg), vitamin E (7.5 IU), caffeine (200mg), quercetin aglycon (50mg) and comprise Epigallo-catechin gallate (EGCG) (30mg), epicatechin (35mg), L-Epicatechin gallate (90mg), epigallocatechin (90mg) and remove the green-tea extract of caffeinum green tea catechin mixture (30mg).With aforementioned mixture food mixer vigorous stirring.Then with pure water and orange juice with this mixture diluted to 1L, make the orange juice that comprises 10% percentage by weight in the last solution.
In a development test, suffer from high cholesterol and hypertensive 4 male sex and 4 female subjects with preparation 2 treatments.Every experimenter drinks 1 vial formulation 2 (20fl.oz., or 591mL) every day and continues 10.Then, half (1 male subject with 3 female subjects) continues to drink every day 1 bottle of identical preparation and continues 20 in this group.Second half then stopped this kind therapeutic scheme 5 days in the group, began to drink every day 2 bottles of same preparation then and continued 20.The result shows that all experimenters' concentrated force and mood all are improved.Cholesterol levels and blood pressure also drop in the normal range (NR).Do not observe significantly on one's body the experimenter and to lose weight.Respectively there is an experimenter during studying, to feel thirsty in two groups.
In another development test, two male subject and two female subjects continue 1 month every day and drink 2 vial formulations 2 (every bottle of 20fl.oz.).The result shows that all experimenters' mood and sexual desire all are improved.All experimenters' body weight all experiences alleviating in 10-25 pound (2-6% of the body weight) scope.After therapeutic scheme finished, most subjects had anxious state of mind.
In another research test, suffer from a male sex and three female subjects of serious constipation with preparation 3 treatments.Every experimenter continued for 1 every day in week and drinks 1-3 vial formulation 3 (every bottle of 20fl.oz.).All experimenters' constipation is all alleviated.
In another research test, suffer from Crohn's disease (Crohn ' s disease) and have the male subject of stomachache and symptom of diarrhea to use preparation 3 to treat for one.This patient drinks 2 vial formulations 3 (every bottle of 20fl.oz.) every day, continues a week.Two kinds of symptoms all significantly alleviate and effect still kept at least 1 week after therapeutic scheme finishes.
Other specific embodiments
The disclosed feature of all these specifications all can be united in any form.Feature disclosed in this specification can have, and feature identical, equal or similar purpose replaces.Therefore, unless offer some clarification on, disclosed feature only is an example in series of equivalent or the similar features in all these specifications.
According to the disclosed content of this specification, have the knack of those skilled in the art scholar and can confirm substantive characteristics of the present invention easily for any one, and do not breaking away under its spirit and the scope, can make different changes to the present invention and make it meet different purposes and situation with modification.Therefore, other specific embodiments is also contained in the following claims.

Claims (16)

1. composition, it comprises vitamin B1, vitamin B2, vitamin B3, vitamin B6, cobalamin, vitamin C, caffeine, Quercetin, Epigallo-catechin gallate (EGCG), epicatechin, L-Epicatechin gallate, epigallocatechin and remove caffeinum green tea catechin mixture, wherein the weight ratio of each composition is the 0.1-50 vitamin B1,0.1-150 vitamin B2,0.1-2000 vitamin B3,0.1-200 vitamin B6,0.005-0.15 cobalamin, the 50-2000 vitamin C, the 50-1500 caffeine, the 20-2000 Quercetin, the 10-500 Epigallo-catechin gallate (EGCG), 10-500 epicatechin, 10-500 L-Epicatechin gallate, 10-500 epigallocatechin, 10-500 remove a few theine mixtures of caffeinum green tea.
2. composition as claimed in claim 1, it further comprises vitamin E.
3. composition as claimed in claim 1, it further comprises CoQ-10, isoflavones, taurine, beet pectin fiber or ginkgo biloba extract.
4. composition as claimed in claim 2, it further comprises CoQ-10, isoflavones, taurine, beet pectin fiber or ginkgo biloba extract.
5. composition as claimed in claim 1, wherein said composition are dried forms.
6. composition as claimed in claim 2, wherein said composition are dried forms.
7. composition as claimed in claim 3, wherein said composition are dried forms.
8. composition as claimed in claim 4, wherein said composition are dried forms.
9. composition as claimed in claim 1, wherein said composition are tea, soft drink, fruit juice, milk, coffee, biscuit, cereal based food, chocolate or snack food.
10. composition as claimed in claim 2, wherein said composition are tea, soft drink, fruit juice, milk, coffee, biscuit, cereal based food, chocolate or snack food.
11. composition as claimed in claim 3, wherein said composition are tea, soft drink, fruit juice, milk, coffee, biscuit, cereal based food, chocolate or snack food.
12. composition as claimed in claim 4, wherein said composition are tea, soft drink, fruit juice, milk, coffee, biscuit, cereal based food, chocolate or snack food.
13. composition as claimed in claim 1 is used for the treatment of Crohn's disease, arthritis, leukaemia, sex dysfunction or chronic constipation in preparation; Improve notice or mood; Or the application in the medicine of reduction cholesterol levels or blood pressure.
14. application as claimed in claim 13, wherein said composition further comprises vitamin E.
15. application as claimed in claim 13, wherein said composition further comprise CoQ-10, isoflavones, taurine, beet pectin fiber or ginkgo biloba extract.
16. application as claimed in claim 14, wherein said composition further comprise CoQ-10, isoflavones, taurine, beet pectin fiber or ginkgo biloba extract.
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