CN1107680C - Solasodine hydrochlorate and productive method and application in medicine - Google Patents
Solasodine hydrochlorate and productive method and application in medicine Download PDFInfo
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- CN1107680C CN1107680C CN 00129122 CN00129122A CN1107680C CN 1107680 C CN1107680 C CN 1107680C CN 00129122 CN00129122 CN 00129122 CN 00129122 A CN00129122 A CN 00129122A CN 1107680 C CN1107680 C CN 1107680C
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- ethanol
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- solasodine
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- methyl alcohol
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Abstract
The present invention relates to an active and new compound solasodine hydrochloride with the functions of resisting cancer and inflammation, and relieving asthma, and a molecular structure disclosed in the drawing, a production method for the solasodine hydrochloride, and the application of the solasodine hydrochloride as a new medicine source for a traditional medicine to two formulations of oral liquor and an injection for resisting cancer and inflammation, and relieving asthma.
Description
The present invention relates to a kind of new compound solasodine hydrochloride and production method thereof and in pharmaceutically application.
Existing black nightshade and the Chemical Composition of Australian eggplant, the separation method of solasodine and the research of drug activity both at home and abroad, solasodine is water insoluble, is dissolved in methyl alcohol, chloroform and hot ethanol, has anti-inflammatory, anti-S
180, rising blood sugar effect, toxic side effect is big, content is low, is pharmaceutically using as yet so far, its four kinds of glycosides account for more than 80% of total alkali, no anticancer, anti-inflammatory action only uses as sterilant on agricultural.Its leaching process complexity, agents useful for same is many, danger is big, seriously polluted, production cycle length, separation difficulty, can't use.
It is strong to the purpose of this invention is to provide a kind of drug activity, toxic side effect is little, water soluble, stable in properties, new compound solasodine hydrochloride and production method thereof that production method is easy, and as a kind of source new drugs in pharmaceutically application, to replace those weak curative effects, the existing medicine that toxic side effect is big benefits the people.
Principle of the present invention be according to the structure activity relationship of medicine will not have anticancer, relieving asthma, four kinds of glycosides α-solasonines, β-solasonine, γ-solasonine, the solamargine hydrolysis of the solasodine of anti-inflammatory activity, make the alkaloid that becomes unbound state with the alkaloid of sugared bonding state, make its generation have 3-hydroxyl anticancer, anti-inflammatory activity.Again with the secondary amino group salify on the 6th ring in the molecule, the drug activity group on its molecule precursor structure that polarizes by force makes anticancer, the antiphlogistic drug activity of its maintenance and enhancing 3-hydroxyl, and the polarity of its molecule, solvability, stability strengthen simultaneously.Activate its molecule drug activity, with the secondary ammonium alkali that causes on 3-hydroxyl and the 6th ring, two active groups coexist as with the constructional feature among a part, and two active groups interact, and make its molecule produce new drug activity antiasthmatic effect again.
Its reaction is as follows:
Solanidine-S R=H α-solasonine
β-solasonine
γ-solasonine
Solamargine
1, compound solasodine hydrochloride of the present invention has following structure and nature and characteristic:
(1) molecular structure of solasodine hydrochloride:
Molecular formula: C
27H
44NO
2Cl molecular weight: 448.08
(2) physico-chemical property solasodine hydrochloride is a kind of trilateral sheet crystallization (ethanol), and 300 ℃ do not reach the preceding decomposition of fusing point, [α] 20
D=-2.2 (water), soluble in water, acetic acid solution, be insoluble to high density methyl alcohol, ethanol, be insoluble to organic solvents such as acetone, benzene, ether, sherwood oil.
(3) drug activity
1. antitumour activity solasodine hydrochloride 200mg/kg can significantly suppress nuclear fission, can make HeLa cytoclasis to behind mice transplanted tumor inhibiting rate 〉=65%, 12 hour, and obvious cytotoxicity is arranged.Clinical trial certificate, injection concentration are 50mg/ml, and the 10-30ml solasodine hydrochloride aqueous solution is to lung cancer, liver cancer, mammary cancer, and 7-10 obtains obvious effects in day.Cooperate operation medication curative effect better.
2. antiasthmatic activity solasodine hydrochloride 150mg/kg, oral or abdominal injection, the cavy asthma that can significantly bring out to antihistaminic.Clinical trial certificate, capsule that the solasodine hydrochloride is made or tablet, every,, contain solasodine hydrochloride 100mg only, day is obeyed secondary, each 2-3 sheet, grain, dyspnea disappears or obviously disappears in 20-30 minute, and vital capacity obviously increases, toot the sound of roaring obviously reduces, and complexion, breathes and drives in normally.Heavily suffer from 2-3 and can normally walk down in day, blood pressure, heart are also made moderate progress.
3. anti-inflammatory activity solasodine hydrochloride 150mg/kg filling stomach or abdominal injection can significantly resist the mouse foot swelling that carrageenin causes; Clinical trial certificate, tablet that the solasodine hydrochloride is made or capsule, every, contain solasodine hydrochloride 100mg only, day is obeyed secondary, each 2-3 sheet, grain, white corpuscle in the pneumonia, pulmonary tuberculosis, mazoitis, tonsillitis, pharyngitis, trachitis three days is obviously reduced, and inflammation obviously disappears, and 4-7 drives in day substantially in normally.
2, the production method of solasodine hydrochloride
Of the present invention a kind of have more anticancer, relieving asthma, the production method of Chinese medicine one kind new medicine source solasodine (Salasadine) hydrochloride of anti-inflammatory activity, be that life, the half ripe with Solanaceae nightshade black nightshade (Salanum NigrumL) and Australian eggplant (Salanum aviculare Farst) really is raw material.
Accompanying drawing 1 is the process flow sheet of production method of the present invention, below in conjunction with accompanying drawing in detail production method of the present invention is described in detail:
(1) with national inventing patent " production method of the concentrated black nightshade fruit juice " patent No.: The production method of ZL 94 1 04239.1 patentee Liu Liang: with giving birth to really or the half ripe fruit of black nightshade or Australia eggplant Press juice through fragmentation, juice, slag separate, and thick juice is through acidic ethanol extraction, sedimentation or smart filter, reduced pressure concentration or add Enzyme hydrolysis, sterilization, acidic ethanol extract, sedimentation or smart filter, reduced pressure concentration; Pomace is leached with acidic ethanol Rear separation, immersion liquid sedimentation or smart filter reduced pressure concentration are made concentrated black nightshade fruit juice or Australia eggplant inspissated juice.
(2) the colloid thing in the separation inspissated juice: add 4-8 to concentrated black nightshade fruit juice or Australia eggplant inspissated juice Doubly 60-100% ethanol or methyl alcohol and the high degree of agitation of (volume) amount make solution be cream colour to yellowish-brown color contamination Till the turbid liquid, supernatant is got in placement, sedimentation.
(3) extraction of thick TA hydrochloride: the extraction of thick TA hydrochloride has two kinds of methods:
1. supernatant reduced pressure concentration, bath temperature 40-90 ℃, vacuum 0.08-0.095Mpa is to pitchy Viscous liquid proportion 1.09-1.45g/ml gets secondary concentration fruit juice, with secondary concentration fruit juice in room temperature or ice Place cooling in the case and fold the crystallization of thick TA hydrochloride.
2. supernatant is put in room temperature or-10-20 ℃ refrigerator in cooling separate out thick TA hydrochloride knot Crystalline substance leaches crystallization, and filtrate decompression is concentrated into the pitchy viscous liquid, and cooling folds crystallization, again to containing The ethanol or the methyl alcohol that add 80-100% in the secondary concentration fruit juice of crystallization are arranged, stir make solution to turbidity Greatly, place sedimentation, get supernatant, under-10-20 ℃ temperature, fully leach crystallization, crystallization 80-after the cooling 100% ethanol or methanol wash 2-3 time, suction strainer, the dry slightly total biological crystal of hydrochloride that gets.
(4) refining: as thick TA hydrochloride to be recrystallized with ethanol or first alcohol and water, to get always biological Alkali salt hydrochlorate elaboration, main component are α-solasonine hydrochloride, β-solasonine hydrochloride, and γ-The solasonine hydrochloride, solamargine (solamargine) hydrochloride, solasodine (solasodine) Hydrochloride. For soluble in water, the crystal of insoluble high concentration ethanol, methyl alcohol.
(5) hydrolysis: with the aqueous hydrochloric acid solution dissolving of total alkali hydrochloride usefulness 2.5-8% or earlier with after the little water dissolving The 2.5-8% hydrochloric acid solution that adds ethanol or methyl alcohol transfers to ethanol or methyl alcohol is the solution of the 2.5-8% hydrochloric acid of 50-80% Gu: liquid (1: 20-100), heating water bath is to boiling 2 hours, add while hot 80-100% ethanol or methyl alcohol as The Oslasodine hydrochloride crystallization stops to add alcohol, and being heated to boils makes dissolving crystallized, adds on a small quantity as not dissolving Water makes it till all dissolvings, to boil, stopped heating, cooling, or add up alkali salt hydrochlorate input amount after the cooling 1-5% activated carbon decolorizing or absorption impurity, cool off under normal temperature to boil five minutes heat filtering, filtrate and to analyse Go out the Oslasodine hydrochloride crystallization, to be crystallizedly separate out fully, leach crystallization, with 80-100% ethanol or methyl alcohol Wash dry thick Oslasodine hydrochloride crystallization 1-3 time.
(6) sediment is processed: sediment dissolves with little water, adds 60-100% ethanol or methyl alcohol to mixed Turbid, quiescent settling is got supernatant and is evaporated to thick shape, adds 80-100% ethanol or methyl alcohol, and placement is analysed Go out crystallization, filtrate concentrating adds alcohol to not having till the crystallization again.
(7) refining: with ethanol or the first alcohol and water Oslasodine hydrochloride elaboration that is recrystallized to get.
Also available Oslasodine hydrochloride column chromatography for separation method is refining, and concrete operations are as follows:
With 1.0g Oslasodine hydrochloride and 5g silica G mixing, tablet forming, splitter (4: 3) benzene: Methyl alcohol is washed post, and sheet is put in the splitter top of being equipped with through 1 hour silica G of 110 ℃ of activation, uses benzene: first Alcohol (4: 3) solvent, chromatographic column occurred clearly after flow velocity 2 seconds/(using vacuum degree control) launched A chromatographic band. Be eluant, eluent with 50% ethanol, repeated isolation is collected each chromatographic band and is flowed out as stated above Liquid, each efflux of reduced pressure concentration gets a kind of white crystal.
Oslasodine hydrochloride is a kind of easy molten water, acetic acid, low-concentration ethanol, low concentration methanol, is insoluble to The white triangles shape flat crystal (ethanol) of acetone, chloroform, ethyl acetate, benzene, stable in properties.
The Oslasodine hydrochloride purity of producing with said method 〉=90%, yield (dry product calculating) 〉=1.2 %, the Oslasodine hydrochloride structure is:Fusing point, the front 300 ℃ of decomposition of fusing point.
3, the solasodine hydrochloride is in pharmaceutically application
(1) antitumous effect solasodine hydrochloride 200mg/kg can significantly suppress nuclear fission, can make HeLa cytoclasis to behind animal transplanting tumor inhibiting rate 〉=65%, 12 hour, and obvious cytotoxicity is arranged; Clinical experiment shows, solasodine hydrochloride 50mg/ml, and the 10-30ml injection liquid, evident in efficacy to lung cancer, liver cancer, mammary cancer.
(2) anti-inflammatory action solasodine hydrochloride 100mg/kg mouse stomach, abdominal injection can obviously resist sufficient the swelling of mouse that carrageenin causes; Clinical trial certificate, the solasodine hydrochloride is to pneumonia, pulmonary tuberculosis, mazoitis, tonsillitis, pharyngitis, trachitis injection or oral, and daily 2 times, solasodine hydrochloride net weight 〉=300mg is evident in efficacy at every turn.
(3) antiasthmatic effect solasodine hydrochloride 150mg/kg can significantly bring out cavy asthma to antihistaminic; Face to treat and experimental results show that, oral or injection day medication 2-3 time, only contain solasodine hydrochloride 200-300mg at every turn, to the onset in 15-30 minute of immunity asthma, working lipe 〉=24 hour, heavily suffer from the walking of can leaving the bed in 2-3 days, dyspnea on most beds, wheezing sound disappears or disappear substantially, vital capacity obviously increases, medication is clearly better 7 days (course of treatment), coughs, phlegm, inflammation obviously alleviates or disappear.
The solasodine hydrochloride is a kind of Chinese medicine one kind new medicine with significantly anticancer, anti-inflammatory, antiasthmatic effect, and its purposes is mainly used in the medicine manufacturing of the following disease of treatment:
(1) manufacturing of cancer therapy drug:
1. treat the injection manufacturing of liver cancer, lung cancer, mammary cancer.
2. treat the oral preparations manufacturing of liver cancer, lung cancer, mammary cancer.
(2) manufacturing of suppressing panting calming medicine:
1. the injection manufacturing of anti-immune asthma
2. the manufacturing of anti-immune asthma oral preparations
(3) manufacturing of anti-inflammatory drug
1. treat the injection manufacturing of pneumonia, pulmonary tuberculosis, trachitis, tonsillitis, mazoitis, pharyngitis.
2. treat the oral preparations manufacturing of pneumonia, pulmonary tuberculosis, trachitis, tonsillitis, mazoitis, pharyngitis.
In sum, solasodine hydrochloride of the present invention is crystallization soluble in water, stable in properties, have extremely strong anticancer, anti-inflammatory, the isoreactivity of relievining asthma, toxic side effect is little, can be used for the pharmacy of multiple formulation, helps using, the production technique of solasodine hydrochloride is easy and simple to handle, Device-General, agents useful for same is nontoxic, and valency is low easily to be reclaimed, with short production cycle, be beneficial to Application and Development.
Embodiment 1: take by weighing that the 500kg black nightshade gives birth to, half ripe really removes foreign material, use the pulverizer fragmentation, add hydrochloric acid 95% ethanol of 200kg PH1-2, stirs after 30 minutes placement leach 4 hours centrifugal, tell acid immersion liquid.Pomace is again with the hydrochloric acid 95% ethanol leaching of 100kg PH1-2, centrifugally tells immersion liquid, and pomace is shone dry grinding and makees feed and use.Merge twice acidic ethanol immersion liquid, place sedimentation 24 hours, get the supernatant liquor concentrating under reduced pressure, 70 ℃ of bath temperatures, vacuum tightness 0.09Mpa heats up in a steamer ethanol before the recovery, and being concentrated into proportion is 1.26mg/ml, brownish black viscous liquid, gets concentrated black nightshade fruit juice 41kg.
In being the concentrated black nightshade fruit juice of 1.26mg/ml, proportion adds in the 250kg95% ethanol thread slowly and high degree of agitation, be emulsion to solution, normal temperature was placed 3-4 hour down, get supernatant liquor, in-10-20 ℃ refrigerator and cooled but 24 hours, the crystallization of black nightshade total alkaloids hydrochloride is fully separated out, and suction strainer is told crystallization, and filtrate decompression is concentrated into viscous liquid and gets secondary concentration fruit juice 15kg.In secondary concentration fruit juice, add 60-80% and reclaim ethanol 50kg, stirring constantly separates out the crystallization of dark brown mucolysis black nightshade total alkaloids hydrochloride, be put in but (condition is the same) filtration of refrigerator and cooled, suction strainer, tell coarse crystallization, crystallization is with 95% washing with alcohol three times, thick black nightshade total alkaloids hydrochloride crystallization 2140g.
Make with extra care 2140g black nightshade total alkaloids hydrochloride crude product is put in 50L
3In the ceramic jacket reactor, add 15.0L
3Water makes it dissolving, adding 95% ethanol to crystallization separates out, being heated to boils just dissolves crystallization, stop the heating being cooled to 40-45 ℃, add gac 500g, be heated to boiled 5 minutes after, heat filtering, cooling is to be crystallizedly separated out complete suction strainer with the 5000ml95% washing with alcohol once, dry black nightshade total alkaloids hydrochloride 1640g elaboration.
Hydrolysis is with 1640g black nightshade total alkaloids hydrochloride elaboration 10L
3The 5%HCl aqueous solution is dissolved in 500L
3In the ceramic jacket reactor, add the 80% ethanol 50L that contains 5% hydrochloric acid
3Be heated to and boil 2 hours, adding 95% ethanol to crystallization while hot in still separates out, be heated to and boil, transferred to a little crystallization insoluble till, till adding little water crystallization just being dissolved, be cooled to room temperature, leach crystallization, and with 5000ml 95% washing with alcohol once, the dry solasodine hydrochloride coarse crystallization 991g that gets.
Refining 991g solasodine hydrochloride is dissolved in the 5000ml water, is put in 50L
3In the still, add 95% ethanol to crystallization and separate out, be heated to and boil, make the crystallization dissolving, add 95% ethanol to crystallization again and separate out to be heated to and boil, crystallization is no longer dissolved, and adds a little crystallization dissolving filtered while hot just of water, filtrate is cooled to room temperature, suction strainer, with 95% ethanol 1000ml washing 2 times, dry under room temperature, weighing gets 625g solasodine hydrochloride elaboration, and the envelope bottle is preserved in refrigerator.Productive rate is 1.25 ‰, and calculating productive rate by dry product is 1.25%.
Solasodine hydrochloride column chromatography for separation
With 1.0g solasodine hydrochloride and 5g silica gel G mixing, tablet forming, (separator column (4: 3) benzene: methyl alcohol is washed post) is put in the separator column top of being equipped with through 1 hour silica gel G of 110 ℃ of activation respectively, use benzene: methyl alcohol (4: 3) developping agent, flow velocity 2 seconds/(using vacuum degree control) launches the back chromatographic column and chromatographic band clearly occurs.With 50% ethanol is eluent, and repeated isolation is collected the chromatographic band effluent liquid as stated above, and each effluent liquid of concentrating under reduced pressure gets a kind of white crystal.
Embodiment 2: get that Australian eggplant is given birth to and half-mature fruit 500kg to extract the method for preparing the solasodine hydrochloride from Fructus Solani Nigri identical by above-mentioned, must 611g solasodine hydrochloride elaboration.Productive rate 1.22% is pressed dry product and is calculated productive rate 1.22%.
From two kinds of different raw materials, extract the solasodine hydrochloride silica gel G F for preparing with aforementioned production method
254Plate, benzene: methyl alcohol (4: 3) is developping agent, go in UV-light=254nm under, each a spot, R occur
fValue=0.67 illustrates that every kind of raw material extracts, and the crystallization of preparation is a kind of compound, and two kinds of crystallizations are same substances.
Detect the solasodine hydrochloride with following method:
1. high performance liquid chromatography:
The solasodine hydrochloride aqueous solution is transferred to alkalescence with 5N NaOH, use dichloromethane extraction,, be used to do following experiment after the drying with anhydrous sodium sulfate drying extraction liquid, concentrating under reduced pressure.
Sample after above-mentioned processing by containing the Waters Seppak C18 decontaminating column (Cartrdges) of BondapakC18, is used following condition analysis with the dissolve with methanol of 40% (V/V):
(1) solasodine hydrochloride and solasonine hydrochloride
(temperature is 25 ℃, detects at UV205 for 30CM * 3.9mmi.d.) annotate moving phase with methyl alcohol-0.01M Tris buffered soln (75: 25), flow velocity 2ml/mim at μ BondapaK18.Fig. 2, Fig. 3 provide the standard collection of illustrative plates, Fig. 2 is the chromatography collection of illustrative plates of solasonine and solanidine-S, 1 α among the figure-solasonine, 2 β-solasonine, 3 γ-solasonine, 4 solanidine-Ss, Fig. 3 is the chromatography collection of illustrative plates of solasonine, 1 α among the figure-solasonine, 2 β-solasonine, 3 γ-solasonine.Detected result: appearance time 15min, purity 90.4%.
(2) mensuration of solasodine hydrochloride:
With ethanol-pentane (4: 1) dissolving solasodine (above-mentioned sample is after treatment determined solasodine hydrochloride content with the content of high-efficient liquid phase analysis solasodine) chromatography column 30cm * 4.6cm, load Zorbax SLL (6 μ m), other is furnished with the long pre-column of filling poasilA (37-75 μ m).Moving phase is-hexane: methyl alcohol: acetone (18: 1: 1) flow velocity is imitated ml/min.
Embodiment 3: with the smart purity that claims of balance is 97% solasodine hydrochloride 103.10g, and porphyrize is with mixing behind the heavy powder 30g porphyrize of lactose 67g solubility; Be divided into two parts, every part of each 100g, 100g tabletting machine compressing tablet wherein, every 200mg, get 497 of solasodine hydrochloride sheets, use the plastic-aluminum shrouding, the capsule packing, 24 in every box, every contains solasodine hydrochloride reactive monomer 〉=100mg only, gets solasodine hydrochloride tablet 20 boxes.100g can capsule in addition, every 200mg, 499 of solasodine hydrochloride capsules, pack with plastic-aluminum shrouding, capsule, 24 in every box, every contains solasodine hydrochloride reactive monomer 〉=100mg only, gets solasodine hydrochloride capsule 20 boxes.
Embodiment 4: the smart 103.10g purity that claims is 97% solasodine hydrochloride, under aseptic, be loaded in the peace bottle, every bottle of 515.5mg, the envelope bottle, used peace bottle capacity is 30ml ± 1ml, gets 200 bottles of solasodine hydrochloride injections, the capsule packing, 10 in every box, every contains solasodine hydrochloride reactive monomer 〉=500mg only, gets solasodine hydrochloride injection 20 boxes.
Claims (3)
1, the solasodine hydrochloride compound of a kind of following general formula (I):
2, the production method of the compound of claim 1, this method may further comprise the steps:
(1) with black nightshade or Australian eggplant give birth to fruit or the half ripe fruit is pressed juice through fragmentation, juice, slag separate, thick juice is through acidic ethanol extraction, sedimentation or smart filter, concentrating under reduced pressure or add enzymic hydrolysis, sterilization, acidic ethanol extraction, sedimentation or smart filter, concentrating under reduced pressure; Pomace is made concentrated black nightshade fruit juice or Australian eggplant fruit juice concentrate with acidic ethanol leaching back separation, immersion liquid sedimentation or smart filter concentrating under reduced pressure;
(2) separate colloid thing in the fruit juice concentrate: add the 60-100% ethanol or the methyl alcohol of 4-8 times of volume to fruit juice concentrate, be stirred to till the fruit juice muddiness;
(3) extracting method of thick total alkaloids hydrochloride has two kinds of methods;
1. supernatant liquor is evaporated to proportion 1.09-1.45g/ml, room temperature placement or refrigerator and cooled are but placed and are separated out crystallization;
2. supernatant liquor is placed or-10～20 ℃ of coolings down in room temperature, told crystallization, filtrate decompression is concentrated add alcohol to precipitation again, crystallization is told in the supernatant liquor cooling again, precipitates ethanol or methyl alcohol that used alcohol is 80-100%;
(4) refining water and ethanol or recrystallizing methanol;
(5) hydrolysis with the total alkali hydrochloride with the dissolving of the aqueous hydrochloric acid of 2.5-8% or to transfer to ethanol or methyl alcohol with the 2.5-8% hydrochloric acid soln that adds ethanol or methyl alcohol after the little water dissolving earlier be that the solution of 2.5-8% hydrochloric acid of 50-80% is solid: liquid 1: 20-100, heating in water bath is to boiling 2 hours, adding 80-100% ethanol or methyl alcohol while hot separates out as the solasodine crystal of hydrochloride, stop to add alcohol, being heated to boils makes the crystallization dissolving, as do not dissolve add less water and make it all dissolvings till, to boiling, stop heating, cooling, or the cooling back adds up activated carbon decolorizing or the absorption impurity of the 1-5% of alkali salt hydrochlorate input amount, to the five minutes heat filterings that boil, filtrate is cooled off down in normal temperature and is separated out the solasodine crystal of hydrochloride, to be crystallizedly separate out fully, leach crystallization, with 80-100% ethanol or methanol wash 1-3 time, dry thick solasodine crystal of hydrochloride;
(6) throw out is handled and use water dissolution, adds 60-100% ethanol or methyl alcohol and precipitates once more, adds the alcohol placement behind the supernatant liquor concentrating under reduced pressure and separates out crystallization, till repeating to be extracted into no crystallization and separating out;
(7) refining with ethanol or first alcohol and water recrystallization, also available silica gel G chromatographic separation is purified, and used developping agent is stupid; Methyl alcohol 4: 3, eluent are 50% ethanol.
3, the compound of claim 1 anticancer in preparation, relieving asthma, the purposes in the antiphlogistic medicine.
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| CN100340570C (en) * | 2003-11-29 | 2007-10-03 | 刘良 | Solasodine salt of organic acid, its preparation method and application in medicine |
| CN102643326B (en) * | 2012-04-25 | 2014-03-26 | 广东固升医药科技有限公司 | 3,6-dihydroxyl-22(27)imino-4-furan sterene and preparation method and application thereof |
| JP2020203856A (en) * | 2019-06-17 | 2020-12-24 | 株式会社ダイセル | Method for producing tomatidine-containing extract |
| CN114848663A (en) * | 2022-05-09 | 2022-08-05 | 河南省人民医院 | Application of natural compound Solamargine and anti-HBV (hepatitis B virus) pharmaceutical composition |
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