CN104257770A - Application of total anthraquinone and composition thereof to treatment of Alzheimer's diseases - Google Patents
Application of total anthraquinone and composition thereof to treatment of Alzheimer's diseases Download PDFInfo
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- CN104257770A CN104257770A CN201410503852.2A CN201410503852A CN104257770A CN 104257770 A CN104257770 A CN 104257770A CN 201410503852 A CN201410503852 A CN 201410503852A CN 104257770 A CN104257770 A CN 104257770A
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- emodin
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- A—HUMAN NECESSITIES
- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/708—Rheum (rhubarb)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/90—Plate chromatography, e.g. thin layer or paper chromatography
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Abstract
The invention relates to an application of total anthraquinone and a composition thereof to treatment of Alzheimer's diseases. The total anthraquinone comprises free anthraquinone, combined anthraquinone, anthrone, sugar, tannin or a mixture of the materials.
Description
Technical field:
The present invention relates to a kind of therapeutic use of Chinese medicine extract preparation, particularly a kind of total Radix Et Rhizoma Rhei anthraquinone extracted using Chinese herb rhubarb is as the total Radix Et Rhizoma Rhei anthraquinone preparation of active constituents of medicine and new therapeutic use thereof.
Background technology:
Radix Et Rhizoma Rhei is one of conventional Chinese medicine, is the dry root welding technology of Polygonaceae herbaceos perennial sorrel, Rheum tanguticum or Rheum officinale.
Radix Et Rhizoma Rhei bitter in the mouth, cold in nature, have and rush down lower attack, clearing away heat-fire, removing pathogenic heat from blood and toxic substance from the body, effect of eliminating blood stasis and inducing menstruation.Modern chemistry research proves that the main chemical compositions of Radix Et Rhizoma Rhei is anthraquinone analog compound; The extraction separation method of effective rhubarb component mainly contains: decocting method (water extraction): decocting method is the traditional extraction process of effective rhubarb component, because the polarity of dissociated anthraquinone class is little, thus not good to the extraction effect of dissociated anthraquinone constituents with decocting method; And its combined anthraquinone glycoside polarity is comparatively large compared with its aglycon, therefore available water is extracted.Alcohol extracting method: because the polar contribution of active component in Radix Et Rhizoma Rhei is very wide, therefore with regard to the extraction of general anthraquinone class, the efficiency of alcohol extracting method will apparently higher than decocting method.Alcohol extracting method comparatively conventional at present has ethanol refluxing process and percolation.
Radix Et Rhizoma Rhei complex chemical composition, chemical constitution is by least existing 136 kinds that illustrate, but its main component is anthraquinone analog compound, total content is 2% ~ 5%, wherein free hydroxyanthraquinone compounds only accounts for 1/10 ~ 1/5, being mainly chrysophanol, emodin, aloe-emodin, physcione and chrysophanic acid etc., is the main antimicrobial component of Radix Et Rhizoma Rhei.Associativity anthraquinone derivative is glucoside (i.e. chrysophanol monoglucoside, emodin monoglucoside, aloe-emodin monoglucoside, Rhein Glucoside etc.) and the dianthracene ketoside class of dissociated anthraquinone, be Radix Et Rhizoma Rhei mainly rush down lower composition, wherein dianthracene ketoside is: Sennoside A, B, C, D, E etc.The isomer each other of Sennoside A and sennoside B; Sennoside C and sennoside D isomer each other.In addition the two glucosides still containing emodin, aloe-emodin and chrysophanol.Radix Et Rhizoma Rhei is also containing tannins about 5%, and wherein having galloyl glucose, gallic acid, d-catechin and tetrarin etc., is astringing to arrest bleeding effective ingredient.
The drug effect of Radix Et Rhizoma Rhei and total Radix Et Rhizoma Rhei anthraquinone has report in many documents, and main effect has:
(1) furuncle and phyma and stomatitis, (2) leg ulcer (ecthyma) under, (3) intestinal tympanites, (4) infectious eczematoid dermatitis, (5) (6) acute gastroduodenal of coughing is hemorrhage, (7) chronic renal insufficiency, (8) postoperative hemorrhage (9) of having tooth pulled out is burnt, (10) acute necrotizing enteritis causes enteroparalysis, (11) biliary tract ascarid, (12) acute icterohepatitis, (13) the stomach cancer hemorrhage, (14) acute pancreatitis, (15) tonsillitis (acute suppurative tonsillitis), (1S) mumps, (17) neonate is not sucked the breast, (18) chronic prostatitis, (19) epistaxis, (20) chronic constipation, (21) infantile anorexia, (22) hepatic encephalopathy, (23) Acute Cerebral Hemorrhage, (24) hemobilia, (25) brain traumatic intracranial hemorrhage, (26) hyperlipemia, (27) chronic renal failure, (28) acute cholecystitis, (29) acute ileus, (30) abscess of appendix, (31) tension vesicle, (32) retroperitoneal hematoma, (33) herpes zoster, (34) ovulation function imbalance, (35) acute gonorrhea, (36) psoriasis, (37) acute soft tissue injury, (38) paronychia, (39) lymphoid tuberculosis, (40) old simple obesity, (41) Apoplectic Constipation, (42) difficulty in urination, (43) Complicated by Extensive Burn disease is controlled in advance, (44) hepatitis gravis, (45) epidemic hemorrhagic fever digestive tract hemorrhage.
In a word, Radix Et Rhizoma Rhei and anthraquinones extract thereof have diversified drug effect, are one of Chinese medicine that Recent study is maximum.
The medicine prepared with Radix Et Rhizoma Rhei has gone on the market for many years, and existing rhubarb preparation has xinqingning tablet and new clear Yiganning capsule, and its main component is Radix Et Rhizoma Rhei.There is heat-clearing and toxic substances removing.Blood circulation promoting and blood stasis dispelling, laxation effect.For interior solid heat,
larynxit is swollen,
toothbitterly, conjunctival congestion, constipation, dysentery, infective inflammation, the cards such as fever.
Main active because of Radix Et Rhizoma Rhei is total Radix Et Rhizoma Rhei anthraquinone, therefore there is report using total Radix Et Rhizoma Rhei anthraquinone as ingredient and corresponding extraction separation method more, total Radix Et Rhizoma Rhei anthraquinone extracts the rhizome from Radix Et Rhizoma Rhei, its color shape is brownish black extractum or brown powder crystallization, is the mixture such as dissociated anthraquinone, combined anthraquinone, anthrone, sugar, tannin.
The total Radix Et Rhizoma Rhei anthraquinone preparation gone on the market has total Radix Et Rhizoma Rhei anthraquinone capsule, and its main component is Radix Et Rhizoma Rhei extract.[function cures mainly] is used for the treatment of damp-heat jaundice hepatitis.
Chinese Patent Application No.: 200810107381.8 applyings date: 2008-11-13 discloses a kind of preparation method for the treatment of damp-heat jaundice hepatitis total Radix Et Rhizoma Rhei anthraquinone capsule, wherein the Main Ingredients and Appearance of total Radix Et Rhizoma Rhei anthraquinone capsule is Radix Et Rhizoma Rhei active ingredient compositions total Radix Et Rhizoma Rhei anthraquinone, and press total Radix Et Rhizoma Rhei anthraquinone 18%-22%, the proportioning of starch 78%-82% is prepared
The indication of the present inventor to total Radix Et Rhizoma Rhei anthraquinone preparation is studied, and finds unexpectedly, and total Radix Et Rhizoma Rhei anthraquinone preparation of the present invention may be used for treating senile dementia, and achieves gratifying effect.
Summary of the invention:
The invention provides a kind of new treatment use of total Radix Et Rhizoma Rhei anthraquinone preparation, total Radix Et Rhizoma Rhei anthraquinone of the present invention comprises Radix Et Rhizoma Rhei anthraquinone material prepared by any one method, comprises dissociated anthraquinone, combined anthraquinone, anthrone, sugar, tannin etc. or their mixture.The total Radix Et Rhizoma Rhei anthraquinone mentioned in following Chinese patent, Radix Et Rhizoma Rhei anthraquinone or Radix Et Rhizoma Rhei anthraquinone analog derivative:
99114211.X the method extracting Radix Et Rhizoma Rhei total free anthraquinones
00125405.7 1 kinds of extractum and preparation methoies extracting dissociated anthraquinone from Radix Et Rhizoma Rhei
01113574.3 extracts the method for dissociated anthraquinone and medicinal novelty teabag thereof from Radix Et Rhizoma Rhei
The method for extraction and purification of 01134161.0 total Radix Et Rhizoma Rhei anthraquinone and the application in treatment renal failure medicine thereof
The extraction process of 02114573.3 Rheum aboveground vegetation part anthraquinones
200610057160.5 the method for a supercritical carbon dioxide extraction total Radix Et Rhizoma Rhei anthraquinone
200610001899.4 the method for extracting rhubarb powder dissociated anthraquinone by supercritical acid hydrolysis
200610128443.4 the optimised process of the anthraquinone component in Radix Et Rhizoma Rhei is extracted in cell ultrasonication
200610067506.X the improved method of synthesizing of an emodin
200710068891.4 the method adopting SCF-CO 2 high purity rhubarb free anthraquinone
200810059316.2 the method for an extraction separation of total anthraquinone compounds
200810107377.1 one kind is extracted the method for total Radix Et Rhizoma Rhei anthraquinone from Radix Et Rhizoma Rhei
200810135343.3 the preparation method of a total free anthraquinones extract from rhubarb
200910272509.0 extract the method for highly purified chrysophanic acid from roots and stems of rhubarb
200910307312.6 the separation method of rhubarb-combined anthraquinone and rhatannin
200910272508.6 the separation method of a high-purity emodin
200910157905.9 a Radix Et Rhizoma Rhei extract and Synthesis and applications thereof
201110086108.3 the method for a ultrasonic extraction of rhubarb anthraquinone-type components
201110112289.2 the Extraction and separation method of a rhubarb anthraquinones component
The method of rhubarb anthraquinone 201310292063.4 rhubarb medicinal material self enzymatic isolation method dissociates
201110112290.5 the method for the total Radix Et Rhizoma Rhei anthraquinone in supercritical extraction Chinese herb rhubarb
201310191913.1 a Radix Et Rhizoma Rhei extract and application thereof
201310110849.X one kind is separated the method for emodin with cocrystallization
201310243667.X the method extracting general anthraquinone from new fresh Radix et Rhizoma Rhei
Total Radix Et Rhizoma Rhei anthraquinone of the present invention, most preferably adopts total Radix Et Rhizoma Rhei anthraquinone prepared by following methods:
Its preparation method is as follows: step 1,
Get Radix Et Rhizoma Rhei 1000g, according to the percolation under Chinese Pharmacopoeia version in 2010 annex I0 fluid extract and extractum item, with ethanol as solvent, flood after 48 hours, with the speed slowly percolation of per kilogram medicated powder 1 ~ 1.5ml per minute, collect the liquid 5000ml that just filters for subsequent use; Continue percolation, collect continuous liquid 10000ml decompression recycling ethanol to 60 DEG C relative density 0.90 ~ 0.9 of filtering, let cool, leave standstill, filter, obtain precipitate I, filtrate 1 is for subsequent use;
Step 2,
Get liquid of just filtering and add 50% ethanol dilution to alcohol content 75%, alkalize to liquid of filtering without gallic acid speckle with 65% alcoholic solution of 10% sodium hydroxide, leave standstill 12 hours, get supernatant salt acid for adjusting pH value to 6.0 ~ 7.0, decompression recycling ethanol to 60 DEG C relative density 1.00 ~ 1.02, lets cool, leave standstill, filter, obtain precipitate 1 and filtrate 2
Step 3,
Filtrate 2 and filtrate 1 merge, be evaporated to 80 DEG C of relative densities 1.40 ~ 1.45, add the alcohol reflux 2 times of 6 times of thick paste weight, each 0.5 hour, filter, filtrate is alkalized to solution without gallic acid speckle with 65% alcoholic solution of 10% sodium hydroxide, leave standstill 12 hours, filter, filtrate adjust ph to 6.0 ~ 7.0, decompression recycling ethanol, being concentrated into 80 DEG C of relative densities is 1.45 ~ 1.48, and merge with above-mentioned precipitate 1, weighed weight, add 10 times amount 0.5% sodium hydrate aqueous solutions to dissolve, concentrated hydrochloric acid adjust ph to 6.0 ~ 7.0, add the gelatin of 0.2 times of consolidated material weight, heating, being concentrated into 80 DEG C of relative densities is 1.40 ~ 1.45, slowly add 4 times amount ethanol while hot, heated and stirred is separated out to gelatin, filter, collecting precipitation and filtrate, precipitation adds proper amount of boiling water, heating makes dissolving, 80 DEG C of relative densities are made to be 1.40 ~ 1.45, slowly add 4 times amount ethanol while hot, heated and stirred is separated out to gelatin, filter, collecting precipitation and filtrate, precipitate repetitive operation again 1 time, merge 3 filtrates, decompression recycling ethanol to 60 DEG C relative density 0.95 ~ 0.97, let cool, filter, collect precipitate II and filtrate 3,
Step 4,
Filtrate 3 checks that tannin is to negative, adds 4 times amount alcohol settling and eliminates residual gelatin, filters, reclaims ethanol, evaporate to dryness, 85 DEG C, 0.07MPa drying under reduced pressure, pulverizes, adds 6 times of dry substance w ethanol and reflux 2 times, each 0.5 hour, merge ethanol, decompression recycling ethanol, obtains residue
Step 5,
Residue and precipitate I, precipitate II merge, and mixing, less than 65 DEG C drying under reduced pressure, obtain total Radix Et Rhizoma Rhei anthraquinone of the present invention.
Total Radix Et Rhizoma Rhei anthraquinone of the present invention, its detection method is as follows:
Its [character] is brownish yellow powder, feeble QI, mildly bitter flavor.
Its [discriminating] method is as follows: get total Radix Et Rhizoma Rhei anthraquinone 0.1g of the present invention, adds chloroform 40ml supersound process 10 minutes, and filter, filtrate is as need testing solution.Separately get aloe-emodin, chrysophanol, physcione, emodin, chrysophanic acid reference substance, add dissolve with methanol, make every 1ml respectively containing 0.2mg, 0.1mg, 0.1mg, 0.1mg, the solution solution in contrast of 0.2mg, test according to thin layer chromatography (Chinese Pharmacopoeia version in 2010 annex VIB), draw above-mentioned two kinds of test samples and each 5 ~ 10 μ l of reference substance solution put respectively in same with Sodium Tvlose be adhesive silica gel H lamellae on (newly activating), the upper solution of placing with less than 10 DEG C, petroleum ether (30 ~ 60 DEG C) Ethyl formate one formic acid (15:5:1) is for developing solvent, launch below 25 DEG C, take out, dry, inspect under putting ultra-violet lamp (365nm).In test sample chromatograph, on the position corresponding to reference substance chromatograph, the fluorescence speckle of aobvious same color.
Its [inspection] method is as follows:
The inspection of gallic acid: get total Radix Et Rhizoma Rhei anthraquinone fine powder 25mg of the present invention, put in 5ml measuring bottle, adds methanol 4 ~ 5ml supersound process and makes dissolving in 30 minutes, and cooling, adds methanol dilution to scale, filters, gets subsequent filtrate, as need testing solution.Separately get gallic acid reference substance, add methanol and make the solution of every 1ml containing 0.1mg, product solution in contrast, according to thin layer chromatography (Chinese Pharmacopoeia version in 2010 annex VIB) test, draw each 5 μ l of above-mentioned two kinds of solution and put respectively on same silica gel g thin-layer plate, with toluene-ethyl acetate-formic acid (5:4:1) for developing solvent, launch, take out, dry, spray with 1% ferric chloride alcoholic solution.In test sample chromatograph, on the position corresponding to reference substance chromatograph, the spot colors of appearance should be deeper than the color of reference substance speckle.The inspection of ponticin: get total Radix Et Rhizoma Rhei anthraquinone 0.2g of the present invention, add methanol 2ml, warm macerating 10 minutes, lets cool, and gets supernatant 10ul point on filter paper, launch with 45% ethanol, take out, dry, place 10 minutes, inspect under putting ultra-violet lamp (365nm), lasting bright purple fluorescence must not be shown.
Its [assay] method is as follows:
(1), general anthraquinone
The preparation of reference substance solution
Get emodin reference substance and be about 10mg, accurately weighed, put in 100ml measuring bottle, add methanol dilution to scale, shake up, to obtain final product.
The preparation of standard curve: precision measures reference substance solution 0ml, 0.1ml, 0.2ml, 0.4ml, 0.8ml, 1.2ml, 1.6ml put in 10ml tool plug test tube, be evaporated to dry, residue respectively precision adds 0.8% magnesium acetate methanol solution 10ml and makes dissolving, shake up, with first part for blank, according to ultraviolet one visible spectrophotometry (Chinese Pharmacopoeia version in 2010 annex VA), absorbance is measured at the wavelength place of 510nm, take absorbance as vertical coordinate, concentration is abscissa, drawing standard curve.
Algoscopy: get this product and be about 40mg, accurately weighed, put in flask at the bottom of 100ml garden, add 8% hydrochloric acid solution 20ml, then add chloroform 20mL and to put in boiling water bath reflux 1 hour, cooling, put in separatory funnel, with a small amount of chloroform washing container to colourless, be incorporated in separatory funnel, divide and get chloroform layer, acid solution uses chloroform extraction 3 times (20ml, 15ml, 10ml) again, merge chloroform extraction liquid to put in 100ml measuring bottle, add chloroform and be diluted to scale, shake up.Precision measures 0.4ml and puts in 10ml tool plug test tube, be evaporated to dry, residue respectively precision adds 0.8% magnesium acetate methanol solution 10ml and makes dissolving, shakes up, with first part for blank, according to ultraviolet one visible spectrophotometry (Chinese Pharmacopoeia version in 2010 annex VA), measure absorbance at the wavelength place of 510nm, measure absorbance in accordance with the law, read the amount of general anthraquinone in test sample from standard curve, calculate, to obtain final product.
This product is pressed dry product and is calculated, containing general anthraquinone with emodin (C
15h
loo
5meter, should be 50%-60%).
(2), dissociated anthraquinone
The preparation of reference substance solution
Get emodin reference substance and be about 10mg, accurately weighed, put in 100ml measuring bottle, add methanol dilution to scale, shake up, to obtain final product.
The preparation of standard curve: precision measures reference substance solution 0ml, 0.1ml, 0.2ml, 0.4ml, 0.8ml, 1.2ml, 1.6ml put in 10ml tool plug test tube, be evaporated to dry, residue respectively precision adds 0.8% magnesium acetate methanol solution 10ml and makes dissolving, shake up, with first part for blank, according to ultraviolet one visible spectrophotometry (Chinese Pharmacopoeia version in 2010 annex VA), absorbance is measured at the wavelength place of 510nm, take absorbance as vertical coordinate, concentration is abscissa, drawing standard curve.
Algoscopy: get this product and be about 40ml, accurately weighed, put in 100ml conical flask, add chloroform and be about 60ml supersound process (power 250W, frequency 25KHz) 40 minutes, let cool, filter, rinse filter and conical flask with chloroform, be incorporated in filtrate, filtrate is transferred in 100ml measuring bottle, adds chloroform and is diluted to scale, shake up.Precision measures 0.4ml and puts in 10ml tool plug test tube, be evaporated to dry, residue respectively precision adds 0.8% magnesium acetate methanol solution 10ml and makes dissolving, shakes up, with first part for blank, according to ultraviolet one visible spectrophotometry (Chinese Pharmacopoeia version in 2010 annex VA), measure absorbance at the wavelength place of 510nm, measure absorbance in accordance with the law, read the amount of dissociated anthraquinone in test sample from standard curve, calculate, to obtain final product.
This product is pressed dry product and is calculated, containing dissociated anthraquinone with emodin (C
15h
loo
5) meter, should be 48%-58%.
(3), aloe-emodin, chrysophanic acid, emodin, chrysophanol, physcione total amount: measure according to high performance liquid chromatography (China is to allusion quotation version in 2010 annex VID).
Chromatographic condition and system suitability with 18 a heatable brick bed base silicon a heatable brick bed bonded silica gels for filler; With methanol-0.1% phosphoric acid solution (85:15) for mobile phase: determined wavelength is for 440nm.Number of theoretical plate calculates should be not less than 3000 by emodin peak.
Aloe-emodin is got in the preparation of reference substance solution, chrysophanic acid, emodin, chrysophanol, physcione reference substance are appropriate, accurately weighed, add methanol and make the mixed solution of every 1ml containing aloe-emodin, chrysophanic acid, each 10 μ g of emodin, physcione 20 μ g, chrysophanol 50 μ g, to obtain final product.
The preparation of need testing solution: get this product and be about 15mg, accurately weighed, put in 100ml measuring bottle, add methanol appropriate, supersound process (power 250W, frequency 25KHz) 30 minutes, make it dissolve, take out, let cool, add methanol dilution to scale, shake up, filter, precision measures subsequent filtrate 10ml (residual filtrate is for subsequent use), put in flask, fling to solvent, add 8% hydrochloric acid solution 20ml and add chloroform 20ml reflux 2 hours again, let cool, put in separatory funnel, with a small amount of chloroform washing container, be incorporated in separatory funnel, divide and get chloroform layer, acid solution extracts 3 times with chloroform jolting again, when each 10, merge chloroform liquid, decompression and solvent recovery is to dry, residue adds methanol to be made dissolving and is transferred in 10ml measuring bottle, add methanol to scale, shake up, filter, get subsequent filtrate, obtain.
Algoscopy is accurate respectively draws reference substance solution and each 20 μ l injection liquid chromatographies of need testing solution, measures, to obtain final product.
This product is pressed dry product and is calculated, containing aloe-emodin (C
15h
30o
5), chrysophanic acid (C
15h
8o
6), emodin (C
15h
10o
5), chrysophanol (C
15h
10o
4), physcione (C
16h
12o
5) total amount must not be less than 50%.
(4) free aloe-emodin, free chrysophanic acid, Free Emodin, free chrysophanol, Free Emodin methyl ether total amount measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 annex VID).
Measure according to high performance liquid chromatography (China is to allusion quotation version in 2010 annex VID).
Chromatographic condition and system suitability with 18 a heatable brick bed base silicon a heatable brick bed bonded silica gels for filler; With methanol-0.1% phosphoric acid solution (85:15) for mobile phase: determined wavelength is for 440nm.Number of theoretical plate calculates should be not less than 3000 by emodin peak.
Aloe-emodin is got in the preparation of reference substance solution, chrysophanic acid, emodin, chrysophanol, physcione reference substance are appropriate, accurately weighed, add methanol and make the mixed solution of every 1ml containing aloe-emodin, chrysophanic acid, each 10 μ g of emodin, physcione 20 μ g, chrysophanol 50 μ g, to obtain final product.
The preparation of need testing solution: get this product and be about 15mg, accurately weighed, put in 100ml measuring bottle, add methanol appropriate, supersound process (power 250W, frequency 25KHz) 30 minutes, makes it dissolve, take out, let cool, add methanol dilution to scale, shake up, filter, a part for filtrate is as need testing solution.
Algoscopy: accurate absorption reference substance solution and each 20 μ l injection liquid chromatographies of need testing solution respectively, measure, to obtain final product.
This product is pressed dry product and is calculated, containing free aloe-emodin (C
15h
30o
5), free chrysophanic acid (C
15h
8o
6), Free Emodin (C
15h
10o
5), free chrysophanol (C
15h
10o
4), Free Emodin methyl ether (C
16h
12o
5) total amount must not be less than 40%.
Total Radix Et Rhizoma Rhei anthraquinone of the present invention, wherein,
Containing general anthraquinone in emodin, be 50%-60%.
Containing dissociated anthraquinone in emodin, be 48%-58%.
Calculate, containing aloe-emodin (C by dry product
15h
30o
5), chrysophanic acid (C
15h
8o
6), emodin (C
15h
10o
5), chrysophanol (C
15h
10o
4), physcione (C
16h
12o
5) total amount be no less than 50%.
Calculate by dry product, containing free aloe-emodin (C
15h
30o
5), free chrysophanic acid (C
15h
8o
6), Free Emodin (C
15h
10o
5), free chrysophanol (C
15h
10o
4), Free Emodin methyl ether (C
16h
12o
5) total amount be no less than 40%.
Total Radix Et Rhizoma Rhei anthraquinone of the present invention can be prepared into tablet, the oral pharmaceutical forms such as capsule, also can be prepared into external and injectable drug form, the tablet prepared as the component containing following part by weight or capsule:
Preparation method is as follows:
1) total Radix Et Rhizoma Rhei anthraquinone, microcrystalline Cellulose, mix homogeneously;
2) by the dissolve with ethanol of polyvidone with 95% (v/v), the povidone solution (polyvidone of 10 parts of weight is dissolved into the polyvidone alcoholic solution obtaining 100 parts of volumes in the ethanol of 95%) containing 10% is prepared into;
3) povidone solution of 10% is added in said mixture stir, soft material processed, cross 18 mesh sieve granules, dry, add magnesium stearate after particle drying and mix, fill 1000 capsules.Or upper tablet machine presses 1000, then coating.
The present invention is unexpected in the process of research total Radix Et Rhizoma Rhei anthraquinone finds that it can be used for treating senile dementia, and core of the present invention is for this reason, provides a kind of use of approved drugs for nonapproved uses, namely prepares a kind of medicine being used for the treatment of senile dementia with total Radix Et Rhizoma Rhei anthraquinone of the present invention.
Below by way of experimental data, novelty teabag of the present invention is described.
1, total Radix Et Rhizoma Rhei anthraquinone is on the impact of In vitro culture normal tire Mus Activity of Cortical Neurons
Get the normal kunming mice of conceived 15 days, dislocation of craning one is put to death, and with iodine tincture and 75% alcohol disinfecting, aseptically layering is dissected, and takes out fetal mice, is placed in the dissociation solution D of ice bath
1-SGH (D
1for the PUCK liquid without calcium ion, SGH is Sucrose-Glucose solution and HEPES buffer).Under stereomicroscope, anatomical isolation goes out cerebral cortex, rejects blood vessel and tunicle, is cut into 1mm roughly
3fragment, with 80mg/L Dnasel effect 10min, then softly blows and beats with the thin bore dropper that flame is scraped and organizes agglomerate, make it fully disperse, and draws upper strata cell suspension after leaving standstill.Centrifugal rear use contains blood serum medium (containing the DF of 10% hyclone
12) to be adjusted to by cell density be 1.0 × 10
6individual/mL, is inoculated in 96 orifice plates wrapped in advance by PLL, every hole 100L, in 37 DEG C, and the CO of 5%
2cultivate in incubator.Postvaccinal 3rd day of neurocyte, every hole adds the DF of the MeN061016-1 of 50L variable concentrations
12(final concentration is followed successively by 10molL to liquid
-1, 1molL
-1, 0.1molL
-1, 10nmolL
-1, 1nmolL
-1, 0.1nmolL
-1), matched group adds isopyknic DF
12.Continue cultivation 3 days, every hole adds MTT (Sigma) 15L (1.5gL
-1), hatch 4h for 37 DEG C, Microscopic observation purple acicular crystal, careful supernatant discarded, every hole adds DMSO100L, and ambient temperatare puts 10min, after under mirror, purple crystal all dissolves, MTT absorbance value is measured, determined wavelength 570nm, reference wavelength 630nm with Dynatech MR400ELISA readout instrument.Contrast with method total Radix Et Rhizoma Rhei anthraquinone and, memantine hydrochloride.Result is all checked through SPSS10.0 software One-way ANOVA (one factor analysis of variance).Compared with matched group, the total Radix Et Rhizoma Rhei anthraquinone of each dosage group all significantly can promote normal tire Mus Activity of Cortical Neurons.
2, total Radix Et Rhizoma Rhei anthraquinone is on the impact of In vitro culture normal tire Corium Mus layer neuron survival rate
Normal tire Mus cortical neuron cultural method is the same, containing blood serum medium (containing the DF of 10% hyclone
12) to be adjusted to by cell density be 4.0 × 10
4/ cm
2, be inoculated in 24 plates wrapped in advance by PLL, every hole 0.5mL, in 37 DEG C, the CO of 5%
2cultivate in incubator.Postvaccinal 2nd day of neurocyte, every hole adds the DF of cytosine arabinoside
12(final concentration is 10molL to liquid
-1) effect 24h, to suppress non-neuronal hyper-proliferative.Within 3rd day, every hole adds the DF of the total Radix Et Rhizoma Rhei anthraquinone of 50L variable concentrations
12(final concentration is followed successively by 0.1molL to liquid
-1, 10nmolL
-1, 1nmolL
-1), matched group adds isopyknic DF
12.Change liquid every day 1 time, drug effect concentration is the same.Be cultured to the 7th day, the culture fluid in each hole of sucking-off, adds platform and expects orchid, carries out survived neuronal counting under phase contrast microscope, and 5 visuals field are counted in every hole, amounts to 6 holes.Result is all checked through SPSS 10.0 software One-way ANOVA (one factor analysis of variance).Total Radix Et Rhizoma Rhei anthraquinone significantly can promote normal tire Corium Mus layer neuronal survival, obviously reduces cell mortality.
3, experiment in vivo: total Radix Et Rhizoma Rhei anthraquinone to 20min before improvement result SD female rats training every day of SD female rats learning memory disorder caused by scopolamine, except normal group intraperitoneal injection of saline and model group lumbar injection 3mgkg
-1beyond scopolamine hydrobromide, all the other respectively organize rats by intraperitoneal injection 3mgkg
-1while scopolamine hydrobromide, oral administration gavage total Radix Et Rhizoma Rhei anthraquinone (2.6mg/kg, 13.2mg/kg, 32.9mg/kg), memantine hydrochloride (25mg/kg).Every rat uses MORRIS water maze autographic apparatus (Jie Ou Science and Technology Ltd. provides by Beijing) to position sail training twice, continuous 6 days every day, within the 7th day, carries out space exploration test.Result all carries out the multifactor analysis of variance of repeated measure through the Repeated measure of SPSS 10.0 software General linear model, wherein rat 6 days training grand mean achievement One-way ANOVA (one factor analysis of variance) check.Compare with model group, total Radix Et Rhizoma Rhei anthraquinone (2.6mg/kg, 32.9mg/kg) significantly can shorten the average latency of learning memory disorder SD female rats caused by scopolamine, finds tactful purposiveness and obviously strengthens, and trend formula and orthoscopic ratio increase.
Table 1 total Radix Et Rhizoma Rhei anthraquinone is on the preclinical impact of SD female rats orientation navigation caused by scopolamine
(n＝7,
)
* P<0.05vs model group, * * P<0.01vs model group, * * * P<0.001vs model group
Table 2 total Radix Et Rhizoma Rhei anthraquinone is on the impact of SD female rats orientation navigation average latency caused by scopolamine
(n＝7,
)
| Group | Six days grand means achievement (s) |
| Normal group | 44.2±15.2 *** |
| Model group | 99.4±9.9 |
| Total Radix Et Rhizoma Rhei anthraquinone 2.6mgkg -1 | 85.5±11.4 * |
| Total Radix Et Rhizoma Rhei anthraquinone 13.2mgkg -1 | 95.1±6.3 |
| Total Radix Et Rhizoma Rhei anthraquinone 32.9mgkg -1 | 81.7±13.5 * |
| Memantine hydrochloride 25mgkg -1 | 98.0±13.2 |
* P<0.05vs model group; * * P<0.001vs model group
In sum, cell in vitro experiment confirms that total Radix Et Rhizoma Rhei anthraquinone significantly can promote original cuiture tire Mus Activity of Cortical Neurons, increase Neuronal Survival quantity, in body, animal test results shows, total Radix Et Rhizoma Rhei anthraquinone significantly can improve the cognitive competence of scopolamine caused memory cognitive disorder rat.Therefore, total Radix Et Rhizoma Rhei anthraquinone can be applicable to treat senile dementia.
Detailed description of the invention:
Further illustrate the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1
The preparation method of the total Radix Et Rhizoma Rhei anthraquinone capsule of invention is as follows:
1) total Radix Et Rhizoma Rhei anthraquinone, microcrystalline Cellulose, mix homogeneously;
2) by the dissolve with ethanol of polyvidone with 95% (v/v), the povidone solution (polyvidone of 10 parts of weight is dissolved into the polyvidone alcoholic solution obtaining 100 parts of volumes in the ethanol of 95%) containing 10% is prepared into;
3) povidone solution of 10% is added in said mixture stir, soft material processed, cross 18 mesh sieve granules, dry, add magnesium stearate after particle drying and mix, fill 1000 capsules.
Embodiment 2
Formula is
Preparation method is as follows:
1) total Radix Et Rhizoma Rhei anthraquinone, microcrystalline Cellulose, mix homogeneously;
2) by the dissolve with ethanol of polyvidone with 95% (v/v), the povidone solution (polyvidone of 10 parts of weight is dissolved into the polyvidone alcoholic solution obtaining 100 parts of volumes in the ethanol of 95%) containing 10% is prepared into;
3) povidone solution of 10% is added in said mixture stir, soft material processed, cross 18 mesh sieve granules, dry, add magnesium stearate after particle drying and mix, press 1000.
Embodiment 3
Formula is
Preparation method is as follows:
1) total Radix Et Rhizoma Rhei anthraquinone, microcrystalline Cellulose, mix homogeneously;
2) by the dissolve with ethanol of polyvidone with 95% (v/v), the povidone solution (polyvidone of 10 parts of weight is dissolved into the polyvidone alcoholic solution obtaining 100 parts of volumes in the ethanol of 95%) containing 10% is prepared into;
3) povidone solution of 10% is added in said mixture stir, soft material processed, cross 18 mesh sieve granules, dry, add magnesium stearate after particle drying and mix, fill 1000 capsules.
Claims (6)
1. total Radix Et Rhizoma Rhei anthraquinone and compositions thereof the application in the medicine of preparation treatment senile dementia.
2. application according to claim 1, wherein said total Radix Et Rhizoma Rhei anthraquinone comprises Radix Et Rhizoma Rhei anthraquinone material prepared by any one method, comprises dissociated anthraquinone, combined anthraquinone, anthrone, sugar, tannin etc. or their mixture.
3. application according to claim 1, wherein said total Radix Et Rhizoma Rhei anthraquinone is the total Radix Et Rhizoma Rhei anthraquinone adopting following methods to prepare:
Step 1,
Get Radix Et Rhizoma Rhei 1000g, according to the percolation under Chinese Pharmacopoeia version in 2010 annex I0 fluid extract and extractum item, with ethanol as solvent, flood after 48 hours, with the speed slowly percolation of per kilogram medicated powder 1 ~ 1.5ml per minute, collect the liquid 5000ml that just filters for subsequent use; Continue percolation, collect continuous liquid 10000ml decompression recycling ethanol to 60 DEG C relative density 0.90 ~ 0.9 of filtering, let cool, leave standstill, filter, obtain precipitate I, filtrate 1 is for subsequent use;
Step 2,
Get liquid of just filtering and add 50% ethanol dilution to alcohol content 75%, alkalize to liquid of filtering without gallic acid speckle with 65% alcoholic solution of 10% sodium hydroxide, leave standstill 12 hours, get supernatant salt acid for adjusting pH value to 6.0 ~ 7.0, decompression recycling ethanol to 60 DEG C relative density 1.00 ~ 1.02, lets cool, leave standstill, filter, obtain precipitate 1 and filtrate 2
Step 3,
Filtrate 2 and filtrate 1 merge, be evaporated to 80 DEG C of relative densities 1.40 ~ 1.45, add the alcohol reflux 2 times of 6 times of thick paste weight, each 0.5 hour, filter, filtrate is alkalized to solution without gallic acid speckle with 65% alcoholic solution of 10% sodium hydroxide, leave standstill 12 hours, filter, filtrate adjust ph to 6.0 ~ 7.0, decompression recycling ethanol, being concentrated into 80 DEG C of relative densities is 1.45 ~ 1.48, and merge with above-mentioned precipitate 1, weighed weight, add 10 times amount 0.5% sodium hydrate aqueous solutions to dissolve, concentrated hydrochloric acid adjust ph to 6.0 ~ 7.0, add the gelatin of 0.2 times of consolidated material weight, heating, being concentrated into 80 DEG C of relative densities is 1.40 ~ 1.45, slowly add 4 times amount ethanol while hot, heated and stirred is separated out to gelatin, filter, collecting precipitation and filtrate, precipitation adds proper amount of boiling water, heating makes dissolving, 80 DEG C of relative densities are made to be 1.40 ~ 1.45, slowly add 4 times amount ethanol while hot, heated and stirred is separated out to gelatin, filter, collecting precipitation and filtrate, precipitate repetitive operation again 1 time, merge 3 filtrates, decompression recycling ethanol to 60 DEG C relative density 0.95 ~ 0.97, let cool, filter, collect precipitate II and filtrate 3,
Step 4,
Filtrate 3 checks that tannin is to negative, adds 4 times amount alcohol settling and eliminates residual gelatin, filters, reclaims ethanol, evaporate to dryness, 85 DEG C, 0.07MPa drying under reduced pressure, pulverizes, adds 6 times of dry substance w ethanol and reflux 2 times, each 0.5 hour, merge ethanol, decompression recycling ethanol, obtains residue
Step 5,
Residue and precipitate I, precipitate II merge, and mixing, less than 65 DEG C drying under reduced pressure, to obtain final product.
4. application according to claim 3, wherein said total Radix Et Rhizoma Rhei anthraquinone contains general anthraquinone in emodin, for 50%-60%, containing dissociated anthraquinone in emodin, be 48%-58%, calculate by dry product, total amount containing aloe-emodin, chrysophanic acid, emodin, chrysophanol, physcione is no less than 50%, calculate by dry product, the total amount containing free aloe-emodin, free chrysophanic acid, Free Emodin, free chrysophanol, Free Emodin methyl ether is no less than 40%
Its [character] is brownish yellow powder, feeble QI, mildly bitter flavor,
Its [discriminating] method is as follows: get total Radix Et Rhizoma Rhei anthraquinone 0.1g of the present invention, add chloroform 40ml supersound process 10 minutes, filter, filtrate is as need testing solution, separately get aloe-emodin, chrysophanol, physcione, emodin, chrysophanic acid reference substance, add dissolve with methanol, make every 1ml respectively containing 0.2mg, 0.1mg, 0.1mg, 0.1mg, the solution solution in contrast of 0.2mg, test according to thin layer chromatography (Chinese Pharmacopoeia version in 2010 annex VIB), draw above-mentioned two kinds of test samples and each 5 ~ 10 μ l of reference substance solution put respectively in same with Sodium Tvlose be adhesive silica gel H lamellae on (newly activating), the upper solution of placing with less than 10 DEG C, petroleum ether (30 ~ 60 DEG C) Ethyl formate one formic acid (15:5:1) is for developing solvent, launch below 25 DEG C, take out, dry, inspect under putting ultra-violet lamp (365nm), in test sample chromatograph, on the position corresponding to reference substance chromatograph, the fluorescence speckle of aobvious same color,
Its [inspection] method is as follows:
The inspection of gallic acid: get total Radix Et Rhizoma Rhei anthraquinone fine powder 25mg of the present invention, put in 5ml measuring bottle, add methanol 4 ~ 5ml supersound process and make dissolving in 30 minutes, cooling, add methanol dilution to scale, filter, get subsequent filtrate, as need testing solution, separately get gallic acid reference substance, add methanol and make the solution of every 1ml containing 0.1mg, product solution in contrast, test according to thin layer chromatography (Chinese Pharmacopoeia version in 2010 annex VIB), draw each 5 μ l of above-mentioned two kinds of solution to put respectively on same silica gel g thin-layer plate, with toluene-ethyl acetate-formic acid (5:4:1) for developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution, in test sample chromatograph, on the position corresponding to reference substance chromatograph, the spot colors occurred should be deeper than the color of reference substance speckle,
The inspection of ponticin: get total Radix Et Rhizoma Rhei anthraquinone 0.2g of the present invention, add methanol 2ml, warm macerating 10 minutes, lets cool, get supernatant 10ul point on filter paper, launch with 45% ethanol, take out, dry, place 10 minutes, inspect under putting ultra-violet lamp (365nm), lasting bright purple fluorescence must not be shown
Its [assay] method is as follows:
(1), general anthraquinone
The preparation of reference substance solution
Get emodin reference substance and be about 10mg, accurately weighed, put in 100ml measuring bottle, add methanol dilution to scale, shake up, to obtain final product,
The preparation of standard curve: precision measures reference substance solution 0ml, 0.1ml, 0.2ml, 0.4ml, 0.8ml, 1.2ml, 1.6ml put in 10ml tool plug test tube, be evaporated to dry, residue respectively precision adds 0.8% magnesium acetate methanol solution 10ml and makes dissolving, shake up, with first part for blank, according to ultraviolet one visible spectrophotometry (Chinese Pharmacopoeia version in 2010 annex VA), absorbance is measured at the wavelength place of 510nm, take absorbance as vertical coordinate, concentration is abscissa, drawing standard curve
Algoscopy: get this product and be about 40mg, accurately weighed, put in flask at the bottom of 100ml garden, add 8% hydrochloric acid solution 20ml, add chloroform 20mL again and to put in boiling water bath reflux 1 hour, cooling, put in separatory funnel, with a small amount of chloroform washing container to colourless, be incorporated in separatory funnel, divide and get chloroform layer, acid solution uses chloroform extraction 3 (20ml again, 15ml, 10ml), merging chloroform extraction liquid puts in 100ml measuring bottle, add chloroform and be diluted to scale, shake up, precision measures 0.4ml and puts in 10ml tool plug test tube, be evaporated to dry, residue respectively precision adds 0.8% magnesium acetate methanol solution 10ml and makes dissolving, shake up, with first part for blank, according to ultraviolet one visible spectrophotometry (Chinese Pharmacopoeia version in 2010 annex VA), absorbance is measured at the wavelength place of 510nm, measure absorbance in accordance with the law, the amount of general anthraquinone in test sample is read from standard curve, calculate, obtain,
(2), dissociated anthraquinone
The preparation of reference substance solution
Get emodin reference substance and be about 10mg, accurately weighed, put in 100ml measuring bottle, add methanol dilution to scale, shake up, to obtain final product,
The preparation of standard curve: precision measures reference substance solution 0ml, 0.1ml, 0.2ml, 0.4ml, 0.8ml, 1.2ml, 1.6ml put in 10ml tool plug test tube, be evaporated to dry, residue respectively precision adds 0.8% magnesium acetate methanol solution 10ml and makes dissolving, shake up, with first part for blank, according to ultraviolet one visible spectrophotometry (Chinese Pharmacopoeia version in 2010 annex VA), absorbance is measured at the wavelength place of 510nm, take absorbance as vertical coordinate, concentration is abscissa, drawing standard curve
Algoscopy: get this product and be about 40ml, accurately weighed, put in 100ml conical flask, add chloroform and be about 60ml supersound process (power 250W, frequency 25KHz) 40 minutes, let cool, filter, filter and conical flask is rinsed with chloroform, be incorporated in filtrate, filtrate is transferred in 100ml measuring bottle, add chloroform and be diluted to scale, shake up, precision measures 0.4ml and puts in 10ml tool plug test tube, be evaporated to dry, residue respectively precision adds 0.8% magnesium acetate methanol solution 10ml and makes dissolving, shake up, with first part for blank, according to ultraviolet one visible spectrophotometry (Chinese Pharmacopoeia version in 2010 annex VA), absorbance is measured at the wavelength place of 510nm, measure absorbance in accordance with the law, the amount of dissociated anthraquinone in test sample is read from standard curve, calculate, obtain,
(3), aloe-emodin, chrysophanic acid, emodin, chrysophanol, physcione total amount: measure according to high performance liquid chromatography (China to allusion quotation version in 2010 annex VID),
Chromatographic condition and system suitability with 18 a heatable brick bed base silicon a heatable brick bed bonded silica gels for filler; With methanol-0.1% phosphoric acid solution (85:15) for mobile phase: determined wavelength is for 440nm, and number of theoretical plate calculates should be not less than 3000 by emodin peak,
Aloe-emodin is got in the preparation of reference substance solution, chrysophanic acid, emodin, chrysophanol, physcione reference substance are appropriate, accurately weighed, add methanol and make the mixed solution of every 1ml containing aloe-emodin, chrysophanic acid, each 10 μ g of emodin, physcione 20 μ g, chrysophanol 50 μ g, obtain
The preparation of need testing solution: get this product and be about 15mg, accurately weighed, put in 100ml measuring bottle, add methanol appropriate, supersound process (power 250W, frequency 25KHz) 30 minutes, make it dissolve, take out, let cool, add methanol dilution to scale, shake up, filter, precision measures subsequent filtrate 10ml (residual filtrate is for subsequent use), put in flask, fling to solvent, add 8% hydrochloric acid solution 20ml and add chloroform 20ml reflux 2 hours again, let cool, put in separatory funnel, with a small amount of chloroform washing container, be incorporated in separatory funnel, divide and get chloroform layer, acid solution extracts 3 times with chloroform jolting again, when each 10, merge chloroform liquid, decompression and solvent recovery is to dry, residue adds methanol to be made dissolving and is transferred in 10ml measuring bottle, add methanol to scale, shake up, filter, get subsequent filtrate, obtain,
Algoscopy is accurate respectively draws reference substance solution and each 20 μ l injection liquid chromatographies of need testing solution, measures, to obtain final product,
(4) free aloe-emodin, free chrysophanic acid, Free Emodin, free chrysophanol, Free Emodin methyl ether total amount measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 annex VID),
Measure according to high performance liquid chromatography (China is to allusion quotation version in 2010 annex VID),
Chromatographic condition and system suitability with 18 a heatable brick bed base silicon a heatable brick bed bonded silica gels for filler; With methanol-0.1% phosphoric acid solution (85:15) for mobile phase: determined wavelength is for 440nm, and number of theoretical plate calculates should be not less than 3000 by emodin peak,
Aloe-emodin is got in the preparation of reference substance solution, chrysophanic acid, emodin, chrysophanol, physcione reference substance are appropriate, accurately weighed, add methanol and make the mixed solution of every 1ml containing aloe-emodin, chrysophanic acid, each 10 μ g of emodin, physcione 20 μ g, chrysophanol 50 μ g, obtain
The preparation of need testing solution: get this product and be about 15mg, accurately weighed, put in 100ml measuring bottle, add methanol appropriate, supersound process (power 250W, frequency 25KHz) 30 minutes, make it dissolve, take out, let cool, add methanol dilution to scale, shake up, filter, a part for filtrate is as need testing solution
Algoscopy: accurate absorption reference substance solution and each 20 μ l injection liquid chromatographies of need testing solution respectively, measure, to obtain final product.
5. application according to claim 1, wherein said total Radix Et Rhizoma Rhei anthraquinone compositions is the tablet of total Radix Et Rhizoma Rhei anthraquinone, capsule.
6. application according to claim 5, wherein said total Radix Et Rhizoma Rhei anthraquinone capsule, its formula is as follows:
Preparation method is as follows:
1) total Radix Et Rhizoma Rhei anthraquinone, microcrystalline Cellulose, mix homogeneously;
2) by the dissolve with ethanol of polyvidone with 95% (v/v), the povidone solution (polyvidone of 10 parts of weight is dissolved into the polyvidone alcoholic solution obtaining 100 parts of volumes in the ethanol of 95%) containing 10% is prepared into;
3) povidone solution of 10% is added in said mixture stir, soft material processed, cross 18 mesh sieve granules, dry, add magnesium stearate after particle drying and mix, fill 1000 capsules, or upper tablet machine presses 1000, then coating.
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Application publication date: 20150107 |