CN101926790A - (-)-epigallocatechin gallate composition and application - Google Patents

Abstract

The invention discloses a medicinal preparation composition prepared from (-)-epigallocatechin gallate (hereinafter referred to as EGCG) and pharmaceutically combinable auxiliary materials and application thereof, in particular to a tablet and capsule composition prepared from the EGCG and the pharmaceutically combinable auxiliary materials for preventing and treating senile dementias and a preparation method thereof. The invention is obviously characterized by providing an oral preparation with safety, effectiveness, controllable quality and convenient use for patients with the senile dementias.

Description

(-)-epigallocatechin gallate composition and purposes

Technical field

The present invention relates to a kind of (-)-epigallocatechin gallate (EGCG) (hereinafter to be referred as EGCG) with pharmaceutically can be in conjunction with adjuvant useful in preparing drug formulations compositions and purposes.

Background technology

Main component is a flavanol compound in the Folium Camelliae sinensis, anthocyanin class, flavonoid, polyphenols such as flavonols and phenolic acids, according to the phenolic substance characteristics, adopt physics and chemical method to extract the total polyphenols made from extra care in the Folium Camelliae sinensis, active component wherein is mainly (-)-epigallocatechin gallate (EGCG) epigallocatechin gallate (EGCG), (-)-epigallo catechin epigallocatechin (EGC), (-)-L-Epicatechin gallate epicatechin gallate (ECG), (+)-epicatechin epicatechin (EC), (+)-nutgall catechin gallic acid ester gallocatechin gallate (GCG) etc.

EGCG is the strongest active component of antioxidant activity in the Folium Camelliae sinensis, is the material base of tea health-care function.The patent of relevant compositions of disclosed EGCG and application mainly comprises: 02111627.X discloses EGCG and has been applied to the medicine for treating tumor thing, can not only suppress tumor cell proliferation, have and make tumor cell be difficult for produce drug resistance and improve the sensitivity effect of tumor cell to medicine simultaneously; 01106982.1 disclose a kind of EGCG injection, be used for the treatment of acute promyelocytic leukemic, chronic myelocytic leukemia, retinoic acid drug resistance promyelocytic leukemia; Cause application in alopecia medicine or the functional food 200410015898.6 disclose a kind of EGCG because of chemotherapy in preparation prevention and treatment; 03816788.3 disclose the purposes that the compositions of EGCG and lactoferrin, vitamin E, vitamin C and carotenoid is used for prevention or treats dental plaque, gingivitis, periodontal disease and oral malodor (halitosis) and strengthen the feed for pet of the intravital oxidation resistance of whole biology; 03819982.3 disclose EGCG and pantethine or compositionss such as its metabolite, phytanic acid, thioctic acid and policosanol are used for the treatment of type 1 diabetes and type 2 diabetes mellitus; 02809782.3 disclosing EGCG mixes with polysaccharide, particularly pectin and forms powder or granule and obtain preparation; 03824662.7 the composition of the group of EGCG, pantethine or its metabolite, phytanic acid, thioctic acid, policosanol and coenzyme q-10 is disclosed, be used for the treatment of or prevent diabetes or obesity in purposes; 200480014636.6 resveratrol, its derivant, metabolite or the analog of EGCG active component disclosed and at least aly be selected from, the anti-inflammatory effect of the pharmaceutical composition of genistein, vitamin E, polyunsaturated fatty acid, gamma-linolenic acid and vitamin K; 200510018522.5 disclose the monomer or the compound preparation of a kind of nasal cavity or mouthspray administration EGCG and the anti-cold virus functional component of ECG; 200610053032.3 disclose the skin anti-aging effect that a kind of catechin (EGCG), Mel, glycerol, EDTA-2Na, 1,3 butylene glycol, oil-solvent preservative, heparin sodium and buffering solution have; 200580002404.3 disclose a kind of green tea extract, Coleus forskohlii extract, Betula platyphylla Suk. extract and Guarana or the treatment of obesity of paraguay tea extract and preparation of associated metabolic syndrome that contains epigallocatechin gallate (EGCG); 200710096434.6 disclosing EGCG mixes with polysaccharide, particularly pectin and forms powder or granule and obtain preparation; 200680038310.6 disclose the purposes of at least a component in making nutraceutical composition of a kind of EGCG of being selected from, hydroxytyrosol, resveratrol and derivant thereof, metabolite or analog, be used for muscle loss, amyotrophic wasting and other related muscles deficiency disorder; 200710094207.X disclose the application of a kind of EGCG in the medicine of the formation rate of preparation control cholelithiasis, reduction bile pigment calculus and cholesterol calculus; 200680038272.4 disclosing at least a composition combination of a kind of EGCG and resveratrol, its derivant, metabolite or analog, to be used for manufacturing delay old and feeble and/or be used for the treatment of or prevent relevant disease of age; 200480042552.3 disclose the skin care compositions of ginseng saponin F 1 and EGCG, suppressed apoptotic method in the epidermis cell; Be used for the treatment of Senile disease 200510036982.0 disclose a kind of EGCG and polyvinylpyrrolidone (PVP-k30) solid dispersion.

Although present disclosed EGCG patent is more, do not see disclosed EGCG preparation compositions patent and other disclosed documents and materials report; State's patents such as the inquiry U.S., Europe and Japan do not see that EGCG is used for the compositions patent of alzheimer disease.In a word, do not see that the EGCG preparation compositions is used to prevent and treat patent and other open source information of alzheimer disease.

Summary of the invention

The object of the invention provides a kind of EGCG and pharmaceutically acceptable adjuvant prepares capsule or tablet composition; Another purpose of the present invention provides the purposes that a kind of EGCG capsule or tablet composition are used for alzheimer disease.

Effective ingredient EGCG of the present invention extracts to make with extra care from Folium Camelliae sinensis, also can come by the semisynthetic method of chemistry, and content range is 90.0%～99.5%, and the EGCG molecular structural formula is as follows:

EGCG raw material of the present invention and acceptable accessories is made capsule or tablet composition mainly includes but not limited to: one or more of filler (or diluent), binding agent, lubricant or fluidizer, antioxidant, pH regulator agent are made, the EGCG preparation compositions is mainly capsule or tablet, wherein capsule is mainly hard capsule, and tablet is ordinary tablet, coated tablet, coated tablet, Film coated tablets, enteric coated tablet, effervescent tablet, chewable tablet, multilayer tablet, dispersible tablet, Sublingual tablet, buccal tablet, implant, solution sheet, slow releasing tablet etc.

Preparation EGCG capsule or the common adjuvant of tablet composition include but not limited to this: (1) filler such as starch, Icing Sugar, dextrin, starch/Icing Sugar/dextrin mixing use, lactose, amylum pregelatinisatum, microcrystalline Cellulose (MCC), mannitol, calcium sulfate (containing two molecular crystalline water), calcium hydrogen phosphate, medicinal calcium carbonate etc.; (2) wetting agent and adhesive such as starch slurry, sodium carboxymethyl cellulose (CMC-Na), hyprolose (HPC), methylcellulose (MC), ethyl cellulose (EC), hypromellose (HPMC), 10%-20% gelatin solution, 50%-70% sucrose solution, 3%-5% 30 POVIDONE K 30 BP/USP 30 (PVP) aqueous solution or alcoholic solution, 1%-75% alcoholic solution, purified water etc.; (3) lubricant or fluidizer such as magnesium stearate, micropowder silica gel, Pulvis Talci, magnesium stearate, hydrogenated vegetable wet goods; (4) antioxidant such as VE, BHA etc.; The pH regulator agent is ethanedioic acid, sodium dihydrogen phosphate etc.

In the EGCG compositions, the weight ratio of EGCG and adjuvant can be 1: 20, such as getting 25mg EGCG, adds the adjuvant tabletting of 500mg or encapsulated, and above-mentioned adjuvant can also can be several mixture for a kind of; As adopt full raw material tabletting or encapsulated, and then the weight ratio of raw material in sheet or capsule is 100%, and adjuvant is 0%, and promptly EGCG can be 1: 0 in the weight ratio of capsule or tablet composition.

The present composition is the oral compositions of often releasing, and also can be slow-releasing and controlled-releasing composition.Sustained and controlled release capsule or sheet adopt controlled slowly releasing adjuncts to make, as adopt insoluble framework material such as EC, polyethylene, polrvinyl chloride (PVC), polypropylene etc. to make insoluble skeleton slow/controlled release sheet; Adopt hydrophilic skeletons such as hydrophilic high molecular material methylcellulose, HPMC to make gel skeleton slow/controlled release capsule or sheet; Adopt waxiness framework material such as hard ester acid, Brazil wax, peak wax, hydrogenated vegetable oil to make the bioerodable skeleton; Also can adopt more than 2 kinds and also can be made into composite material skeleton slow/controlled release capsule or sheet after the mutual mixing such as insoluble waxiness, hydrophilic gel matrix material.

With ECGC is that raw material is made capsule or tablet composition is (-)-epigallocatechin gallate (EGCG) capsule (abbreviating EGCG capsule or Yi Jixiji capsule as) or (-)-epigallocatechin gallate (EGCG) sheet (abbreviating EGCG sheet or Yi Jixi substrate as).

The method for preparing EGCG capsule or sheet can be the direct encapsulated or tabletting of powder after EGCG and the auxiliary materials and mixing, encapsulated or tabletting after also can granulating with adjuvant.For example, get the EGCG raw material, mix in right amount with amylum pregelatinisatum, Lactis Anhydrous, silicon dioxide, sieve, direct compression promptly; Above-mentioned prescription also can mix with adjuvant, adds that 10% starch slurry is granulated, tabletting behind the dry granulate.Above capsule or tablet composition through after the assay was approved, can be put and carry out coating in the coating pan and get EGCG coating capsule or coated tablet.

For damp proof shading, the normal gastric solubility coating material that adopts carries out coating outside tablet, common coating material include but not limited to hypromellose (HPMC), hyprolose, 30 POVIDONE K 30 BP/USP 30 (PVP), polyethylene glycols (PEG), polyethylene acetal diethylamine acetate (AEA), gastric solubility crylic acid resin, Opadry (Opadry), natural macromolecular material zein (zein), polyethylene-vinylpyridine copolymer etc.Coating solution often adds plasticizer, light screening material mixes use, to play satisfied coating effect.

2005 editions one appendix VI B carries out EGCG thin layer discrimination test to EGCG capsule or sheet by Chinese Pharmacopoeia: get this product capsule 's content or sheet, grind, precision takes by weighing about 20mg, adds ethyl acetate 20ml supersound extraction 10 minutes, filter, get filtrate as need testing solution; Other gets the EGCG reference substance, adds acetic acid ethyl dissolution and makes the solution that every 1ml contains 0.5mg, in contrast product solution.Test according to thin layer chromatography (appendix VI B), draw each 10 μ l of need testing solution and reference substance solution, put respectively on same silica gel thin-layer plate, with formic acid: ethyl acetate: methanol (4: 4: 1) is developing solvent, launches, take out, dry, put under the ultra-violet lamp (254nm) and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

This discrimination test method can be according to the thin layer chromatography quality, chromatography condition is adjusted and is changed, as developing solvent, lamellae, test sample and reference substance concentration, point sample amount etc. are adjusted, to reach best chromatography effect.

The inspection method of EGCG capsule or sheet related substance: get test sample under the assay item as need testing solution, it is an amount of that precision is measured need testing solution, is diluted to the solution that contains 2.5ug among every ml with mobile phase, in contrast product solution.According to the chromatographic condition under the assay item, get reference substance solution 20 μ l, inject chromatograph of liquid, regulate instrumental sensitivity, the peak height that makes the main constituent chromatographic peak is the full-scale 10%-20% of monitor, precision is measured reference substance solution, each 20 μ l of need testing solution again, injects chromatograph of liquid respectively, and the record chromatogram is to 3 times of main constituent peak retention time.As showing impurity peaks, desolventize outside the peak maximum contaminant peak area in the chromatogram of need testing solution, must not be greater than reference substance main peak area, be maximum single impurity≤5.0%, each impurity peak area sum must not be greater than 1.6 times of reference substance main peak areas, i.e. total impurities sum≤8.0%.

Present composition related substance can stipulate separately that also a plurality of simple spike impurity are less than setting, as (-)-epigallo catechin epigallocatechin (EGC), (-)-L-Epicatechin gallate epicatechin gallate (ECG), (+)-epicatechin epicatechin (EC), (+)-nutgall catechin gallic acid ester gallocatechin gallate (GCG) etc. are less than 2%, and the total impurities sum is less than 8% etc.

The present invention makes when EGCG is oral often to release compositions, its dissolution test is as follows: getting this product, according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2005 C, second method), is solvent with 0.1mol/L hydrochloric acid solution 900ml, Revolution Per Minute 50 changes, operation was in accordance with the law got solution 10ml and is filtered in the time of 45 minutes, precision is measured subsequent filtrate 2ml, put in the 10ml measuring bottle, add mobile phase and be diluted to scale, shake up, as need testing solution; It is an amount of that other gets the EGCG reference substance, accurate claims surely, makes solution that every 1mL contains 0.05mg product solution in contrast with the mobile phase dilution.According to the method under the assay item, precision is measured need testing solution and each 20 μ l of reference substance solution, injects chromatograph of liquid respectively, the record chromatogram.By the stripping quantity of external standard method with every capsules of main composition calculated by peak area or sheet, limit is 75% of a labelled amount, should be up to specification.Dissolution determination is also with determined by ultraviolet spectrophotometry, and limit is 75% of a labelled amount, should be up to specification.Present composition dissolution is better, can suitably adjust when formulating the dissolution limit, and be 80%, 85%, 90%, 95% etc. of labelled amount as limit.

Adopt the method for EGCG content in high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D) the mensuration compositions as follows: with the octadecylsilane chemically bonded silica is filler, mobile phase is water: methanol: formic acid (73: 23: 1), detect wavelength 278nm, 40 ℃ of column temperatures, flow velocity 1.0ml/min, number of theoretical plate calculate by EGCG should be not less than 2000.

Get this product 10 capsules or sheet, grind, the accurate title, decide (being equivalent to 25mg EGCG approximately), put in the measuring bottle of 25ml, make every 1ml with the mobile phase dilution and contain the solution of 1mg as the test sample mother solution, precision is measured test sample mother solution 2.5ml and is put in the measuring bottle of 50ml, makes every 1ml with the mobile phase dilution and contains the solution of 0.05mg as need testing solution; It is an amount of that other gets the EGCG reference substance, accurate claims surely, makes solution that every 1ml contains 0.05mg product solution in contrast with the mobile phase dilution.Precision is measured 20 μ l and is injected chromatograph of liquid, and the record chromatogram is pressed external standard method with the main constituent calculated by peak area, promptly.By up-to-date " medicine registration management way " at present (office makes No. 28) regulation, when single active ingredient EGCG content greater than 90%, reach new Chinese medicine 1 class (effective ingredient) ingredient requirement, making compositions is new Chinese medicine 1 class preparation; As press the health food declaration then not according to above-mentioned classification restriction.

The invention provides the Orally administered composition of a kind of EGCG of effective dose, is raw material with EGCG, and its day effective dose (in EGCG) is between 50mg to 4000mg, and the final composition effective dose is determined according to pharmacological effect and clinical trial.

Preparation specification of the present invention is by a kind new medicine declaration, and the preparation specification between 25mg～500mg, is 25mg, 50mg, 100mg, 150mg, 200mg, 250mg, 350mg, 400mg, 500mg etc. as capsule or tablet specification in EGCG.Concrete specification can be decided according to the daily dose of pharmacological effect and clinical trial; as adult (60kg) 800mg every day EGCG is dosage; by 4 or 4 of every days; then to be designed to every or every specification be 200mg for new drug prescription; by 8 of every days or 8 administrations, then to be designed to every or every specification be 100mg to the new drug prescription.

In addition, the present composition also comprises the health food (or functional food) and the food that are used to prevent and treat alzheimer disease except that as the drug development.

For understanding the acute toxicity situation of EGCG, we divide 5 groups (10 every group) with mice, and stomach is irritated in the dilution in 1: 1 of EGCG and water, and Continuous Observation 7d calculates tea polyphenols LD ₅₀The LD of EGCG as a result ₅₀Be 2.6g/kg.This dosage is equivalent to more than 100 times of clinical plan consumption (0.7g/60kg/ day) of being grown up, and prompting EGCG toxicity is lower, clinical drug safety.

Reagent: EGCG is provided by the strong holy Pharmaceutical Technology Co., Ltd in Shanghai, meets EGCG and declares the clinical research quality standard.Animal: Kunming mouse, body weight 20 ± 2g, II level (cleaning level).

Get 50 of mices, male and female half and half are divided into 5 groups at random, 10 every group.Fasting 12h before the administration can't help water.Finding out maximum lethal dose by prerun is 5.6g/kg, and minimum lethal dose is 1.8g/kg, presses the dissolving in 1: 1 of EGCG and water weight ratio.Irritate stomach 1 time on the 1st for 5 groups of mices by predetermined dosage respectively.At once observe behavioristics's active situation such as animal feed, activity, hair, feces after irritating stomach, continuously 7d.Record animal toxicity response situation and dead animal distribute.In time perform an autopsy on sb behind the animal dead, if pathologic finding, LD are then carried out in perusal when unusual ₅₀Measurement result is through the computer statistics result.

After stomach was irritated in EGCG administration as a result, the extremity cyanosis successively appearred in the part mice, short of breath, last respiratory arrest death.Show no obvious abnormalities change through dissecting internal organs such as perusal liver, kidney, lung.Calculate through computer by the Bliss method, record the LD of EGCG ₅₀Be 2.6g/kg (seeing Table 1).LD ₅₀The 95% credible 2.17～3.2g/kg that is limited to, be equivalent to adult clinical plan dosage (60kg) every day (0.7g) more than 100 times.

Table 1Bliss method is measured the LD of EGCG ₅₀

By the Bliss method calculate the LD of EGCG ₅₀Be 2.6g/kg, show that EGCG toxicity is very low, this dosage is equivalent to be grown up clinical plan consumption (0.7g/60kg/ day) more than 100 times, and prompting clinical application amount is safer.

In order to prove that this product is used for the drug effect of alzheimer disease, we have done preliminary pharmacodynamic study to effective ingredient EGCG.EGCG one twice-daily is given mouse stomach, do blank with normal saline, this result of the test shows that EGCG has the raising learning and memory of little mouse, prolong stepping into incubation period in the disposable avoidance response case of mice, the decline that delays to remember, prompting EGCG has the effect that promotes study, delays amnesia, helps the prevention and the treatment of alzheimer disease, provides foundation for further research EGCG is used for alzheimer disease.Test method and result are as follows:

Reagent: EGCG is provided by the strong holy Pharmaceutical Technology Co., Ltd in Shanghai, dissolves with the purified water that adds 9 times of amounts during use; Blank group: purified water; Animal: Kunming mouse, body weight 20 ± 2g, II level (cleaning level).

One. improve the pharmacodynamics test of learning and memory of little mouse

1. test method

Get 20 mices are divided into 2 groups at random, 10 every group, one group is the purified water matched group, and another group is the EGCG test group.

Matched group is irritated stomach with normal saline every day, and test group is irritated stomach with EGCG every day, dosage 0.15g/kg, and every day 1 time, 20d after administration finishes, carries out the behavior training continuously.

Adopt trisection radiant type light-dark discrimination labyrinth box, electric shock voltage 30V, the bright maintenance of lamp 15S.Train every day 20 times, two minor ticks, 20～40S writes down the mice correct response rate of every day, and the correct response rate is 90% in 20 times, promptly reaches association's standard, writes down required frequency of training up to standard.

Behavioral indicator adopts Microsoft Excel software to add up, and the result represents that with x ± s t detects, and P＜0.05 is a significant difference.

2. result of the test

2.1EGCG influence to mice behavior correct response rate

By table 2 as seen, along with the carrying out of behavior training, it is all in rising trend that each organizes the correct response rate of mice.The EGCG group was trained the 1st～4 day in behavior, and the correct response rate of animal all is higher than matched group (P＜0.05), and at the 3rd day of the behavior training, animal reached association's standard, apparently higher than the 5th day matched group.Result of the test shows that EGCG can improve learning ability of mice.

Table 2EGCG to the influence of mice correct response rate (%, n=10)

Annotate: compare * * P＜0.01 with matched group; * P＜0.05

2.2EGCG influence to mice required frequency of training up to standard

By table 3 as seen, EGCG treated animal required frequency of training (57.4 ± 18.0) up to standard obviously is less than (92.0 ± 19.7) (P＜0.01) of normal saline matched group.The result shows that EGCG can reduce animal required frequency of training up to standard, improves learning and memory abilities in aging mice.

Table 3EGCG proposes the influence (n=10) of thing to animal required frequency of training up to standard

Annotate: compare with matched group: * * P＜0.01

Two, promote the pharmacodynamic experiment that mouse memory keeps

1. test method

20 mices are divided into 2 groups at random, and each 10, one group is physiology saline control group; Another group is for EGCG treatment group, and according to above-mentioned grouping, matched group is irritated normal saline, and the EGCG group is irritated the corresponding medicine of stomach every day, and dosage is 0.15g/kg, and once a day, continuous 20 days, administration finished laggard every trade and is training.

Behavior detects adopts disposable passive avoidance response box model, the camera bellows that the avoidance response case is made up of the plastic plate of 25cm * 25cm * 25cm, inner bottom surface is that 3mm, spacing are that the copper grizzly bar of 9mm is formed by diameter, can switch on, the case antetheca has the square door opening of one 10 * 7cm, the platform that connects a 10 * 7cm in front of the door is the place of safety.During experiment camera bellows is placed the desk edge, security platform is unsettled.Mouse tail is placed on the platform towards the camera bellows door, writes down its time of staying on platform, promptly step into incubation period, repeat 3 times, each 12～15min at interval.Next day, carry out formal experiment training, after animal entered camera bellows, (parameter 15mA, electric shock time 5s) immediately shocked by electricity, the electric shock back was detected the index that preclinical length keeps as the animal memory on the the 1st, 6,11 day respectively, incubation period is long more, and memory keeps good more, with 300s as the upper limit, all 300s still do not enter camera bellows, promptly are considered as memory and keep good.Calculate in each group the incubation period 〉=300s person accounts for the percentage of this treated animal, i.e. Ji Yi conservation rate.

Adopt rank test the incubation period of disposable passive avoidance response, the memory conservation rate adopts X 2 test.

2. result of the test

2.1EGCG promote the influence of animal memory

As seen mice is stepped into preclinical influence by table 4, electric shock back the 1st day, the 6th day, the EGCG group is stepped into (P＜0.05 or P＜0.01) that is significantly higher than the normal saline matched group incubation period, electric shock back the 11st day, what EGCG organized steps into incubation period (217.8s) still apparently higher than normal saline matched group (78.6s) (P＜0.05).The result shows: EGCG can obviously prolong animal and step into incubation period.

Table 4EGCG steps into preclinical influence to animal

Annotate: compare with matched group: * * P＜0.01, * P＜0.05

2.2EGCG influence to animal memory conservation rate

By table 5 as seen, electric shock back the 1st day, the 6th day, the 11st day, EGCG group memory conservation rate shows that all apparently higher than normal saline matched group (P＜0.05) EGCG can obviously improve the memory conservation rate of animal (P＜0.05), delays disappearing of animal memory.

Table 5EGCG is to the influence of animal memory conservation rate

Annotate: compare with matched group: * P＜0.05

Outstanding advantage of the present invention has provided a kind of EGCG capsule that safe, quality controllable, easy to use being used to prevent and treat alzheimer disease or compositions of sheet of taking.

The specific embodiment

The preparation of embodiment 1EGCG sheet

Get EGCG raw material 50g (HPLC detects, content 93.8%), add amylum pregelatinisatum 20g, microcrystalline Cellulose 40g, ethanedioic acid 0.1g, silica 1 g, direct pressed powder, the heavy 0.22g (containing EGCG 100mg approximately) of average sheet, specification 100mg, promptly.

Coating pan adds different in nature blank agreement that contracts a film or TV play to an actor or actress 1kg, alcoholic solution coating with 8% Opadry OY-C-700A, 5 rev/mins of coating pan rotating speeds, 40-43 ℃ of sheet bed tempertaure, control hot blast temperature and suitable spray speed, keep unilateral timely drying, about 3 hours of coating makes sheet weightening finish 5%, sifts out the EGCG sheet, that is, below be the tablet testing result.

The capsular preparation of embodiment 2EGCG

Get EGCG raw material 175g (HPLC detects, content 93.8%), add starch 50g, microcrystalline Cellulose 50g, silicon dioxide 2g, high-speed stirred makes mix homogeneously, and is directly encapsulated, the heavy 0.27g (containing EGCG 175mg approximately) of average sheet, specification 175mg, promptly.

On inspection, the maximum single impurity of this capsule: 1.7%, the total impurities sum: 4.2%, dissolution: 93.5%, EGCG content: 98.5%.

The capsular preparation of embodiment 3EGCG

Get EGCG raw material 100g (HPLC detect, content 93.8%), add 75% ethanol and granulate in right amount, drying, directly encapsulated, the heavy 0.38g (containing EGCG 350mg approximately) of average sheet, specification 350mg, promptly.

On inspection, the maximum single impurity of this capsule: 1.7%, the total impurities sum: 4.0%, dissolution: 94.4%, EGCG content: 101.6%.

Claims (11)

1. (-)-epigallocatechin gallate (EGCG) (be called for short EGCG, down with) compositions and purposes comprise that EGCG and combinative adjuvant pharmaceutically make the purposes that oral formulations and said preparation are used to prevent and treat alzheimer disease.

2. (-) as claimed in claim 1-epigallocatechin gallate (EGCG), its chemical structural formula is as follows:

3. EGCG compositions as claimed in claim 1, it is characterized in that EGCG and pharmaceutically the weight ratio of combinative adjuvant be between 1: 0～20.

4. as claim 1,3 described pharmaceutically combinative adjuvants, it is characterized in that adjuvant contains one or more in filler, binding agent, lubricant, antioxidant and the pH regulator agent etc.

5. EGCG compositions as claimed in claim 1, the content that it is characterized in that the EGCG raw material is 90.0%～99.5%.

6. EGCG compositions as claimed in claim 1 is characterized in that the preparation specification in EGCG, is 25～500mg.

7. EGCG compositions as claimed in claim 1 is characterized in that related substance inspection in the preparation quality standard, maximum single impurity≤5.0%, total impurities sum≤8.0%.

8. EGCG compositions as claimed in claim 1 is characterized in that the dissolution limit is respectively more than or equal to 75% of labelled amount in the preparation quality standard, and the result should be up to specification.

9. EGCG compositions as claimed in claim 1 is characterized in that one day dosage of adult of EGCG compositions is counted 50mg to 4000mg with EGCG.

10. EGCG compositions as claimed in claim 1 is characterized in that preparation compositions is a kind of in capsule or the tablet.

11. EGCG compositions as claimed in claim 1 is characterized in that the EGCG compositions is used for prevention and treatment alzheimer disease.