CN109045224A - A kind of sunflower disk semen coicis compound and the purposes in treatment hepatic injury - Google Patents

A kind of sunflower disk semen coicis compound and the purposes in treatment hepatic injury Download PDF

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Publication number
CN109045224A
CN109045224A CN201811264708.2A CN201811264708A CN109045224A CN 109045224 A CN109045224 A CN 109045224A CN 201811264708 A CN201811264708 A CN 201811264708A CN 109045224 A CN109045224 A CN 109045224A
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CN
China
Prior art keywords
semen coicis
sunflower disk
compound
group
liver
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CN201811264708.2A
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Chinese (zh)
Inventor
付学奇
戴惠咛
李婉南
高波
韩露
韩笑
胡峻涵
沈方舟
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Jilin Gete Biotechnology Co Ltd
Jilin University
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Jilin Gete Biotechnology Co Ltd
Jilin University
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Application filed by Jilin Gete Biotechnology Co Ltd, Jilin University filed Critical Jilin Gete Biotechnology Co Ltd
Priority to CN201811264708.2A priority Critical patent/CN109045224A/en
Publication of CN109045224A publication Critical patent/CN109045224A/en
Priority to CN201980071685.XA priority patent/CN113543795A/en
Priority to PCT/CN2019/072318 priority patent/WO2020087784A1/en
Priority to AU2019100729A priority patent/AU2019100729A4/en
Pending legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/899Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A61K36/8994Coix (Job's tears)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/10Preparation or pretreatment of starting material
    • A61K2236/19Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH

Abstract

The present invention provides a kind of sunflower disk semen coicis compound and the purposes in treatment hepatic injury, compound preparation is formed using the sunflower disk and semen coicis of integration of drinking and medicinal herbs, for treating liver damage disease, it solves the problems, such as side effect existing for current existing drug and can not take for a long time, the two acts synergistically and had not only strengthened the reparation of liver, but also promotes the discharge of liver metabolism object.

Description

A kind of sunflower disk semen coicis compound and the purposes in treatment hepatic injury
Technical field
The present invention discloses a kind of sunflower disk semen coicis compound, forms compound preparation by sunflower disk and semen coicis, right It has a significant effect in liver damage disease treatment, belongs to Chinese medicine pharmaceutical technology field.
Background technique
Drug induced hepatic injury has been increasingly becoming the problem of medical and pharmacy can not be ignored, and drug induced hepatic injury refers to drug sheet The damage of immune system caused by hypersensitivity caused by liver function caused by body and its metabolite or its metabolite. The drug of common easy generation drug induced hepatic injury has antibiotic, antituberculotic, Chinese herbal medicine, analgesic-antipyretic, fluothane class fiber crops Liquor-saturated medicine, anti-tumor drug etc..
The existing drug such as interferon for hepatic injury reparation, the exploitation of the drugs such as bicyclic alcohols have become medical attention Problem, but popularization and application is somewhat limited due to price and adverse reaction etc..And integration of drinking and medicinal herbs medicinal material certain herbaceous plants with big flowers The research and development of floral disc semen coicis compound become good natural drug that is a kind of natural and having no toxic side effect.
Be the first application of the present inventor with the immediate technology of the present patent application: CN 108354956A discloses " certain herbaceous plants with big flowers Floral disc extract and its effective component repair the application in wounded hepatocytes drug in preparation ", " sunflower disk extract and its effectively Ingredient has good anti-inflammatory and repair to the wounded hepatocytes as caused by hyperuricemia ";But it was actually using Cheng Zhong, patient occur: arthralgia, diarrhea, the side effects such as low fever affect the therapeutic effect of " sunflower disk extract ".
Summary of the invention
The present invention provides a kind of sunflower disk semen coicis compounds, using the sunflower disk and semen coicis group of integration of drinking and medicinal herbs Solve side effect and nothing existing for current existing treatment liver injury medicament for treating liver damage disease at compound preparation The problem of method is taken for a long time.Present invention demonstrates that the liver cell that semen coicis can assist enhancing sunflower disk extract repairing impaired Ability promotes the discharge of hepatotoxin, at the same can reduce sunflower disk extract individually take caused by side effect, the two has Synergistic effect well.
The present invention provides a kind of sunflower disk semen coicis compounds, it is characterised in that is by following raw material by mass parts Made of number ratio:
Sunflower disk: 25-35 parts;Semen coicis: 15-20 parts of
A kind of sunflower disk semen coicis compound of the present invention, optimum ratio are as follows:
Sunflower disk: 30 parts;Semen coicis: 15 parts.
A kind of sunflower disk semen coicis compound preparation method of the present invention, comprising the following steps:
25-35 parts of step 1) sunflower disk, the deionized water of 20 times of quality is added, is added in 0.2% mass fraction after impregnating sufficiently Property protease in pH6.0-7.0, temperature digest 2 hours under the conditions of being 40-50 DEG C, then adjusting pH to 8,45-50 in reactor DEG C sufficiently reaction 60min, obtain sunflower disk extracting solution;
10-20 parts of step 2 semen coicis, the ethyl alcohol of 20 times of quality is added, impregnates abundant 2h, 45-50 DEG C of sufficiently reaction in reactor 2h obtains semen coicis extracting solution;
Step 3) by gained Aqueous extracts filtering in step 1) and 80-90 DEG C it is outstanding be evaporated, obtain solid powder;
Step 4) by gained alcohol extract filtering in step 2 and 55-60 DEG C it is outstanding be evaporated, obtain solid powder;
Solid powder 2:1 in mass ratio in step 3), step 4) is uniformly mixed by step 5), and 2 times of distilled water dissolutions are made compound Object preparation.
Any pharmaceutical preparation pharmaceutically can be made in a kind of sunflower disk semen coicis compound of the present invention.
Prescription of the present invention is according to as follows:
Based on prescription of the present invention is Chinese medicine record and modern Chinese medicine theory by China's Chinese medicine in relation to treatment liver damage, It is summed up by a large amount of animal experiments and clinical case.
The source of used raw material and effect are as follows in the present invention:
1, sunflower disk, pharmacological property is sweet, nontoxic, trembles with fear, return liver warp, records according to " China's book on Chinese herbal medicine ", function is the flat lung of heat-clearing, and analgesic stops Blood cures mainly headache and dizzy, anti-inflammatory, diuresis, protect liver etc..
2, semen coicis, property slightly sweet flavor is slightly cold, have invigorating spleen to remove dampness, clearing heat and detoxicating, antalgic and inflammation relieving, invigorate the spleen and benefit qi, etc. it is abundant Pharmacological function.
Theory of traditional Chinese medical science thinks that hepatopathy is mostly related with damp evil invasion;While the present invention repairs hepatic injury using sunflower disk, It is acted on using the good dampness elimination of semen coicis, facilitates the excretion of liver metabolism object by diuresis, improve metabolic capability, enhancing is anti- Oxidability prevents purine imbalance oxidation from generating both uric acid sunflower disk semen coicis collaboration auxiliary, plays " clearing damp of getting rid of evils, tonifying spleen altogether The effect of beneficial liver, invigorating the spleen diuresis, clearing heat and detoxicating, antalgic and inflammation relieving ", reinforces the reparation to hepatic injury, and promotes liver metabolism product It is excreted through urine.
The positive effect of the present invention and advantage are:
Compound formulation, the liver that semen coicis can assist enhancing sunflower disk extract repairing impaired is made in sunflower disk and semen coicis The ability of cell while strengthening liver repair ability, and promotes the row of liver metabolism object using the synergistic effect of the two Out, whole comprehensively solve takes the side effects such as arthralgia existing for sunflower disk folk prescription, diarrhea, fever.Through zoopery It is proved with clinical treatment, sunflower disk and semen coicis compound have the function of alleviating hepatic injury, and can adhere to taking for a long time, are mentioning While high repairing effect, the worry of the side effect of folk prescription sunflower disk before this is alleviated.
Detailed description of the invention
Fig. 1, blank control group liver tissue slices;
Fig. 2, model group liver tissue slices;
Fig. 3, positive controls liver tissue slices;
Fig. 4, Semen Coicis extract group liver tissue slices
Fig. 5, sunflower disk extract group liver tissue slices;
Fig. 6,1 group of liver tissue slices of sunflower disk semen coicis compound of the present invention;
Fig. 7,2 groups of liver tissue slices of sunflower disk semen coicis compound of the present invention;
Fig. 8,3 groups of liver tissue slices of sunflower disk semen coicis compound of the present invention.
Specific embodiment
It technical solution and is practiced in order to enable those skilled in the art to better understand the present invention, below with reference to specific experiment The present invention will be further described for example, but lifted experimental example is not as a limitation of the invention.
Embodiment 1
Step 1) sunflower disk 25kg, is crushed to 30 mesh, and the deionized water of 20 times of quality is added, and after impregnating sufficiently, 0.2% matter is added The neutral proteinase of score is measured in pH6.0-7.0, temperature digests 2 hours under the conditions of being 40-50 DEG C, stirs, uses hydrogen Sodium oxide molybdena adjusts PH to 8, and 45-50 DEG C of sufficiently reaction 60min in reactor obtains sunflower disk extracting solution;
Step 2 semen coicis 25kg, is crushed to 30 mesh, and the ethyl alcohol of 20 times of quality is added, and impregnates abundant 2h, 45-50 in reactor DEG C sufficiently reaction 2h, obtain semen coicis extracting solution;
Step 3) by gained Aqueous extracts filtering in step 1) and 80-90 DEG C it is outstanding be evaporated, obtain solid powder;
Step 4) by gained alcohol extract filtering in step 2 and 55-60 DEG C it is outstanding be evaporated, obtain solid powder;
Solid powder 2:1 in mass ratio in step 3), step 4) is uniformly mixed by step 5), and 2 times of distilled water dissolutions are made compound Object preparation.
Embodiment 2
Step 1) sunflower disk 30kg, is crushed to 30 mesh, and the deionized water of 20 times of quality is added, and 0.2% mass is added after impregnating sufficiently In pH6.0-7.0, temperature digests 2 hours the neutral proteinase of score under the conditions of being 40-50 DEG C, stirs, uses hydrogen-oxygen Change sodium and adjust PH to 8,45-50 DEG C of sufficiently reaction 60min in reactor obtains sunflower disk extracting solution;
Step 2 semen coicis 20kg, is crushed to 30 mesh, and the ethyl alcohol of 20 times of quality is added, and impregnates abundant 2h, 45-50 in reactor DEG C sufficiently reaction 2h, obtain semen coicis extracting solution;
Step 3) by gained Aqueous extracts filtering in step 1) and 80-90 DEG C it is outstanding be evaporated, obtain solid powder;
Step 4) by gained alcohol extract filtering in step 2 and 55-60 DEG C it is outstanding be evaporated, obtain solid powder;
Solid powder 2:1 in mass ratio in step 3), step 4) is uniformly mixed by step 5), and 2 times of distilled water dissolutions are made compound Object preparation.
Embodiment 3
Step 1) sunflower disk 35kg, is crushed to 30 mesh, and the deionized water of 20 times of quality is added, and 0.2% mass is added after impregnating sufficiently In pH6.0-7.0, temperature digests 2 hours the neutral proteinase of score under the conditions of being 40-50 DEG C, stirs, uses hydrogen-oxygen Change sodium and adjust PH to 8,45-50 DEG C of sufficiently reaction 60min in reactor obtains sunflower disk extracting solution;
Step 2 semen coicis 15kg, is crushed to 30 mesh, and the ethyl alcohol of 20 times of quality is added, and impregnates abundant 2h, 45-50 DEG C in reactor Sufficiently reaction 2h, obtains semen coicis extracting solution;
Step 3) by gained Aqueous extracts filtering in step 1) and 80-90 DEG C it is outstanding be evaporated, obtain solid powder;
Step 4) by gained alcohol extract filtering in step 2 and 55-60 DEG C it is outstanding be evaporated, obtain solid powder;
Solid powder mass ratio 2:1 ratio in step 3), step 4) is uniformly mixed by step 5), and 2 times of distilled water dissolutions are made multiple Close object preparation.
One, further prove that sunflower disk and Semen Coicis extract have centainly by the anti-inflammatory experiment of following cellular level Anti-inflammatory effect, and the compound of the two has synergistic effect at anti-inflammatory aspect:
1. experiment reagent
Hyclone company of the 1640 culture medium U.S.;
Fetal calf serum Kang Yuan biotech firm;
NEB company of tissue culture plate Britain;
Co., Ltd of RAW264.7 cell (mouse macrophage) Nanjing Keygen Biotech;
Hundred gold medal Biotechnology Co., Ltd of NO Elisa kit;
LPS Sigma Co., USA;
2. drug effect RAW264.7 cell detects antiphlogistic effects by NO level:
(1) by RAW264.7 cell culture in the RPMI 1640 culture medium containing 10% serum, after cell grows to certain amount It carries out secondary culture and freezes;
(2) the RAW264.7 cell of logarithmic growth phase is transferred in 24 orifice plates, and 30,000, every hole cell is containing 10% serum Cultivated in RPMI1640 culture solution, every pore system be 500 μ l, incubation time 1 hour;
(3) need to be separately added into the refreshing particle electuary 30mg/ml of liver, 60mg/ml sunflower disk extract in corresponding aperture according to experiment Each 200 μ l of solution that compound prepared by electuary, embodiment 1, embodiment 2, embodiment 3 is configured, continues culture 3 hours;
(4) LPS of final concentration of 1 μ g/ml is added in the every hole of LPS control group, and the reaction time is 18 hours;
(5) NO kit is taken out from 4 DEG C of refrigerators to be carried out according to kit specification subsequent at room temperature 15-30 minutes Operation;
3. NO secretory volume detects:
(1) sample preparation: the 50 μ l of cell culture medium supernatant of dosing stimulation is drawn;
(2) it is loaded: setting blank well (sample and enzyme marking reagent is not added in blank control wells) gauge orifice respectively and to gaging hole.Standard items Hole accurately adds 50 μ l of standard sample, to 50 μ l of gaging hole plus sample to be tested.Sample is added on ELISA Plate bottom, does not touch hole as far as possible Wall shakes gently uniformly;
(3) it incubates: being placed on 37 DEG C of incubation 30min with sealing plate molding plate;
(4) match liquid: will be spare after 30 times of concentrated cleaning solutions, 30 times of distilled water dilutions;
(5) it washs: carefully taking sealing plate mould off, discard liquid, dry, cleaning solution is filled it up in every hole, is abandoned after standing 30s
It goes, is so repeated 5 times, pat dry;
(6) enzyme: every hole is added 50 μ l of enzyme marking reagent, except blank well;
(7) it incubates: being placed on 37 DEG C of incubation 30min with sealing plate molding plate;
(8) it washs: carefully taking sealing plate mould off, discard liquid, dry, cleaning solution is filled it up in every hole, is discarded after standing 30s, so weight It is 5 times multiple, it pats dry;
(9) develop the color: 50 μ l of color developing agent A is first added in every hole, adds 50 μ L of color developing agent B, gently concussion mix, 37 DEG C be protected from light it is aobvious Color 15min;
(10) terminate: every hole adds 50 μ l of terminate liquid, terminates reaction (blue is vertical at this time turns yellow);
(11) it measures: being returned to zero with blank well, the absorbance (OD value) in each hole of 450nm wavelength measurement;Measurement should be after adding terminate liquid It is carried out in 15min;
4. experimental result
1. each group drug RAW264.7 cell NO inhibiting rate of table compares:
Drug (1mg/ml) NO concentration (pg/ml) Inhibiting rate (%)
Negative control 397.42
Semen Coicis extract 350.12 11.9
Sunflower disk extract 307.14 22.7
Embodiment 1 264.28 33.5
Embodiment 2 257.43 35.2
Embodiment 3 236.55 40.5
Conclusion: In vitro cell experiment shows using RAW264.7 cell detection NO concentration calculation drug antiphlogistic effects, each group drug When concentration is 1.0mg/ml, antiphlogistic effects: embodiment 3 > embodiment, 2 > embodiment, 1 > sunflower disk extract > semen coicis mentions solution Take object, should statistics indicate that, in all drugs, antiphlogistic effects are best for embodiment 3.The experiment also shows individually to make simultaneously Also there are certain antiphlogistic effects with Semen Coicis extract and sunflower disk extract, but the two is used in combination, antiphlogistic effects It is increased with significant, illustrates that the two is used together by a certain percentage with good synergy.
Two, the present invention is further verified using zoopery below to make the reparation of hepatic injury caused by a variety of causes With:
(1) to the reparation of hepatic injury caused by disease (hyperuricemia)
1. experimental animal
SPF grades kunming mice 80,20 ± 2g of weight, the long-living Bioisystech Co., Ltd in Liaoning buys.
2. experiment reagent
Yeast extract (Oxiod company of Britain);
Liver is felt well particle, lot number: Z20027671, Baoding Tianhao Pharmaceutical Co., Ltd.;
Semen Coicis extract;
Sunflower disk extract;
1 gained sunflower disk semen coicis compound of embodiment;
2 gained sunflower disk semen coicis compound of embodiment;
3 gained sunflower disk semen coicis compound of embodiment;
3. modeling and medication
Research carries out title quality to mouse before carrying out, wherein 10 are only used as blank control group, remaining mouse is hyperuricemia mould Type group.Claim quality between daily morning during experiment.The method that model foundation takes yeast extract stomach-filling, by giving a large amount of purine substances Increase its UA value, purine metabolic disturbance, to achieve the effect that temporary raising blood UA value in the short time.By 80 mouse with Machine is divided into 8 groups, and every group about 10, respectively blank control group, model group, positive control (liver feel well particle) group, semen coicis extracts Object group, sunflower disk extract group, example 1 group, 2 groups of embodiment, 3 groups of embodiment.During modeling, except blank control group (waits bodies Ponding stomach-filling) outside, other each group mouse press 20gkg daily-1Yeast extract carries out stomach-filling, 1 d-1, continuous gavage 20d, the 9th Rise day is terminated by 200 μ l/d progress drug stomach-filling to experiment simultaneously, takes murine liver tissue, hepatic tissue section is made and is contaminated with HE Color, the variation of microscopically observation histotomy.(Fig. 1-7)
4. experimental result
Liver tissue slices the result is shown in Figure 1-8, liver cell and hepatic cell cords are clear in lobuli hepatis in blank control group (Fig. 1), liver Cell cytoplasm is full.Liver cell and hepatic cell cords are unintelligible in the lobuli hepatis of the part model group (Fig. 2), and liver cell atrophy is common to be dispersed in The light dye of liver cell cavitation around cell infiltration stove, spotty necrosis stove and accidental central vein has larger wound to liver cell Evil illustrates modeling success.Liver cell and hepatic cell cords are clear in positive drug control group (Fig. 3) lobuli hepatis, accidental to be dispersed in necrosis Stove and cell infiltration.Semen Coicis extract group (Fig. 4) is accidental to be dispersed in spotty necrosis stove and acidophile degeneration.Sunflower disk extract group (Fig. 5) accidental acidophile degeneration has certain repair to liver cell.Example 1 group, 2 groups of embodiment, 3 groups of embodiment (figure 6-8) liver cell and hepatic cell cords are clear in lobuli hepatis, and liver cell cytoplasm is full, and the microstructure prompt present invention passes through sunflower disk Semen coicis compound has more excellent effect compared with sunflower disk single preparations of ephedrine, has better repair to impaired liver cell, Wherein effect most preferably 3 groups of embodiment.
(2) to the reparation of drug-induced hepatic injury
1. experimental animal
SPF grades kunming mice 80,20 ± 2g of weight, No.1 Hospital of Jilin Univ.'s animal experimental center is bought;
2. experiment reagent
Carbon tetrachloride, lot number: 10006428, Sinopharm Chemical Reagent Co., Ltd.;
Liver is felt well particle, lot number: Z20027671, Baoding Tianhao Pharmaceutical Co., Ltd.;
3. testing modeling and medication
80 mouse are randomly divided into 8 groups, respectively blank control group, model group, positive controls, Semen Coicis extract group, Sunflower disk extract group, 1 group of sunflower disk semen coicis compound, 2 groups of sunflower disk semen coicis compound, sunflower disk semen coicis compound 3 groups.Every group 10.The daily normal diet drinking-water of blank control group, remaining group mouse every three daily carry out once abdominal cavity injection 0.5% CCL4 injection, 10 μ l/g of injection dosage.In addition to blank control group each experimental group daily with 200 μ l/ dosage into Row drug stomach-filling, experiment carry out six weeks.Mouse orbit takes blood after experiment, measures glutamic-oxalacetic transaminease (AST), paddy third in serum Transaminase (ALT) content.
Glutamic-oxalacetic transaminease contents level changes in each experimental group serum of table 2.: (U/L)
Group Dosage AST(U/L)
Blank control 200 μ l/ of distilled water is only 30.71±5.16**
Model group 200 μ l/ of distilled water is only 80.16±6.74
Positive drug group Liver feels well 200 μ l/ of particle electuary only 45.62±3.87*
Semen Coicis extract 200 μ l/ obtained by 3 step 2 of embodiment are only 47.94±2.34*
Sunflower disk extract group 200 μ l/ of sunflower disk extract electuary is only 42.15±1.34*
Example 1 group 1 drug of compound, 200 μ l/ is only 38.36±3.31*
2 groups of embodiment 2 drug of compound, 200 μ l/ is only 35.64±2.97**
3 groups of embodiment 3 drug of compound, 200 μ l/ is only 33.20±2.12**
Note: P < 0.01 * P < 0.05 compared with model group, * *.
Conclusion: as can be seen from Table 2, compared with blank control group, in model group serum AST it is horizontal significant increase (* * P < 0.01), illustrate that drug causes seriously to damage to liver, AST horizontal abnormality is caused to increase;It is real in the invention compared with model group Applying AST level in example group serum has reduction (P<0.01 * P<0.05, * *), wherein the horizontal reducing effect of AST: embodiment 3>reality 2 > embodiment of example, 1 > sunflower disk extract > positive drug > Semen Coicis extract is applied, illustrates sunflower disk and semen coicis pair of the invention Drug-induced hepatic injury plays the role of certain repair, and the two is used in combination effect and becomes apparent, wherein embodiment 3 Group AST level illustrates that sunflower disk and semen coicis compound action have synergy, has to liver more preferable already close to normal value Repair.
Glutamic-pyruvic transaminase contents level changes in each experimental group serum of table 3: (U/L)
Group Dosage ALT(U/L)
Blank control 200 μ l/ of distilled water is only 15.71±2.12**
Model group 200 μ l/ of distilled water is only 98.16±1.98
Positive drug group Liver feels well 200 μ l/ of particle electuary only 42.67±4.16*
Semen Coicis extract 200 μ l/ obtained by 3 step 2 of embodiment are only 47.23±2.28*
Sunflower disk extract group 200 μ l/ of sunflower disk extract electuary is only 35.73±4.46*
Example 1 group 1 drug of compound, 200 μ l/ is only 25.19±1.92*
2 groups of embodiment 2 drug of compound, 200 μ l/ is only 22.96±3.62**
3 groups of embodiment 3 drug of compound, 200 μ l/ is only 19.85±3.17**
Note: P < 0.01 * P < 0.05 compared with model group, * *.
Conclusion: as can be seen from Table 3, compared with blank control group, the horizontal significantly raising of model group serum alt (* * P < 0.01), illustrate that drug causes seriously to damage to liver, ALT horizontal abnormality is caused to increase;It is each in the invention compared with model group Administration group serum alt level reduces (P<0.01 * P<0.05, * *), the horizontal reducing effect of AST: 3>embodiment of embodiment 2> 1 > sunflower disk of embodiment extract > positive drug > Semen Coicis extract, illustrates sunflower disk and semen coicis of the invention to drug institute Cause hepatic injury plays the role of certain repair, and the two is used in combination effect and becomes apparent, wherein 3 groups of ALT of embodiment Level illustrates that sunflower disk and semen coicis compound action have synergy, has to liver and preferably repair already close to normal value Multiple effect.
(3) to the repair of alcohol-induced acute hepatic injury
1. experimental animal
SPF grades of Kunming hero mouse 80,20 ± 2g of weight, No.1 Hospital of Jilin Univ.'s animal experimental center is bought.
2. experiment reagent
56 degree of Red Star strong, colourless liquor distilled from sorghum;
Liver is felt well particle, lot number: Z20027671, Baoding Tianhao Pharmaceutical Co., Ltd.;
Semen Coicis extract;
Sunflower disk extract;
1 gained sunflower disk semen coicis compound of embodiment;
2 gained sunflower disk semen coicis compound of embodiment;
3 gained sunflower disk semen coicis compound of embodiment;
3. testing modeling and medication
It is conventional to irradiate daylight after mouse normally raises 5d, it is randomly divided into blank control group, model group, positive controls, semen coicis Extract group, sunflower disk extract extract group, embodiment 1, embodiment 2,3 groups of embodiment, every group 10.Wherein blank control Group and the daily stomach-filling physiological saline of model group mouse, the dosage such as remaining each daily stomach-filling of experimental group (200 μ l/L) drug are continuous to fill 20d is administered in stomach.After last dose 2h, in addition to Normal group stomach-filling same amount of normal saline, each group 56 ° of Red Stars of daily stomach-filling Strong, colourless liquor distilled from sorghum 15ml/kg.Each group in being deprived of food but not water after the last administration.After each group mouse fasting 16h, extracts eyeball and takes blood, Separate the standby survey of serum;
4. biochemical indicator of table detects glutamic-oxalacetic transaminease (AST), glutamic-pyruvic transaminase (ALT) content in mice serum:
Group Dosage AST(U/L) ALT(U/L)
Blank control group 200 μ l/ of distilled water is only 20.53±2.74** 33.95±5.63**
Model group 200 μ l/ of distilled water is only 93.06±7.31 117.36±2.41
Positive drug group Liver feels well 200 μ l/ of particle electuary only 60.63±2.65 84.10±3.67
Semen Coicis extract 200 μ l/ obtained by 3 step 2 of embodiment are only 71.25±1.46 93.29±4.51
Sunflower disk extract group 200 μ l/ of sunflower disk extract electuary is only 58.31±2.98 74.36±1.20
Example 1 group 1 drug of compound, 200 μ l/ is only 46.19±3.17* 63.15±1.79*
2 groups of embodiment 2 drug of compound, 200 μ l/ is only 41.74±1.96* 57.16±3.25*
3 groups of embodiment 3 drug of compound, 200 μ l/ is only 33.23±1.09** 45.58±2.07**
Note: P < 0.01 * P < 0.05 compared with model group, * *.
As can be seen from Table 4, compared with blank control group, in model group serum AST, ALT it is horizontal significant increase (* * P < 0.01);Compared with model group, in the invention embodiment 1-3 group serum alt level significantly reduce (* P < 0.05, * * P < 0.01), the horizontal reducing effect of AST, ALT: 1 > sunflower disk of embodiment 3 > embodiment, 2 > embodiment extract > positive drug group > heart of a lotus seed Seed of jog's tears extract, and 3 groups of embodiment have more obvious decreasing trend than sunflower disk extract group, illustrate sunflower disk of the invention with Semen coicis plays the role of certain repair to drug-induced hepatic injury, and the two is used in combination effect and becomes apparent, 3 groups of AST, ALT levels of middle embodiment illustrate that sunflower disk and semen coicis compound action have synergy already close to normal value, There is better repair to acute alcohol-induced hepatic injury.
Conclusion: sunflower disk semen coicis compound extract is repairing answering in hepatic injury caused by a variety of causes in the present invention With, it is experimentally confirmed, there is good repair with good antiphlogistic effects, while to impaired liver cell, Good reducing effect is all had to AST, ALT level increased extremely.Sunflower disk semen coicis is used in combination, and individually makes compared with the two It is become apparent with curative effect, illustrates that the two has certain synergistic effect, its reparation to damaged liver can be enhanced.And sunflower disk Have the characteristics that the Nantural non-toxic side effect of integration of drinking and medicinal herbs raw material with semen coicis, the two collective effect be take for a long time with repair by Damage liver cell provides effective method.
Three, curative effect of the present invention is further demonstrated that by following typical case
Case 1
Patient Lee, male, 54 one full year of life, patient suffer from gout the year before, and pain redness symptom occurs in toe joint, and local hospital surveys blood Uric acid level 685umol/L, blood uric acid value is reduced to 400umol/L, arthroncus after taking folk prescription sunflower disk extract three months Degree substantially mitigates, but the symptom of low fever continuously emerges during taking, and considers that patient's prolonged illness is weak, taste imbalance, toxic dampness and heat Difficulty is let out, and uses the invention compound instead after two weeks, and blood uric acid value is down to 382umol/L, faster has the function that blood uric acid, While toe joint swelling mitigates, low fever's symptom is also resolved, and is cut out after half a year without recurrence;
Case 2
Patient's week certain, male, 37 one full year of life, blood uric acid value is taken up to the Patients with Hyperuricemia of 871umol/L with arthritic calculus Folk prescription sunflower disk extract after two months stablize to 420umol/L by uric acid level, and occurs with the performance of joint congestion and swelling pain, examines Considering patient's prolonged illness liver kidney metabolic function reduces, and damp and hot turbid heat is difficult to resolve, and metabolite causes local inflammation heap after arthritic calculus dissolution Product, it is difficult to be drained as early as possible by kidney.Compound of the present invention is used instead after 15 days, blood uric acid value is down to 392umol/L, joint Congestion and swelling pain disappears, and continues to take after two weeks, and blood uric acid value is stablized in 370umol/L, and kidney excretion is reinforced, and urination metabolism increases While symptoms of joint pain mitigated, deactivate three months after again without recurrence;
Case 3
The patient Qin, male, 40 one full year of life, blood uric acid value reach the Patients with Hyperuricemia of 769umol/L, mention taking folk prescription sunflower disk Occurs diarrhea, the symptom of low fever during taking object one month, blood uric acid value is reduced to 405umol/L, considers that the long-term high lithemia of patient is led Hepatic and renal function is caused to weaken, damp and hot difficulty is let out, and is given invigorating spleen to remove dampness and is arranged turbid Chinese medicine, after using compound of the present invention instead, takes one week Blood uric acid value is reduced to 350umol/L or so afterwards, continues to take two weeks and cuts out, and blood uric acid value is stablized without recurrence, and diarrhea, The symptom of low fever also disappears therewith.

Claims (5)

1. a kind of sunflower disk semen coicis compound, it is characterised in that be following raw material by made of mass parts ratio:
Sunflower disk: 25-35 parts;Semen coicis: 15-25 parts.
2. a kind of sunflower disk semen coicis compound as described in claim 1, optimum ratio are as follows:
Sunflower disk: 35 parts;Semen coicis: 15 parts.
3. a kind of sunflower disk semen coicis compound preparation method as described in claim 1 or claim 2, including it is following Step:
25-35 parts of step 1) sunflower disk, 30 mesh are crushed to, the deionized water of 20 times of quality is added, are added 0.2% after impregnating sufficiently In pH6.0-7.0, temperature digests 2 hours the neutral proteinase of mass fraction under the conditions of being 40-50 DEG C, stirs, and uses Sodium hydroxide adjusts PH to 8.0, and 45-50 DEG C of sufficiently reaction 60min in reactor obtains sunflower disk extracting solution;
15-25 parts of step 2 semen coicis, 30 mesh are crushed to, the ethyl alcohol of 20 times of quality is added, impregnate abundant 2h, 45- in reactor 50 DEG C of sufficiently reaction 2h, obtain semen coicis extracting solution;
Gained Aqueous extracts filtering in step 1) and 80-90 DEG C of outstanding steaming are obtained solid powder by step 3);
Gained alcohol extract filtering in step 2 and 55-60 DEG C of outstanding steaming are obtained solid powder by step 4);
Solid powder 2:1 in mass ratio in step 3), step 4) is uniformly mixed by step 5), and 2 times of distilled water dissolutions are made compound Object preparation.
4. a kind of sunflower disk semen coicis compound as described in claim 1 is preparing the purposes in liver-injuring drug.
5. a kind of sunflower disk semen coicis compound as described in claim 1 or claim 2 can be made pharmaceutically Any pharmaceutical preparation.
CN201811264708.2A 2018-10-29 2018-10-29 A kind of sunflower disk semen coicis compound and the purposes in treatment hepatic injury Pending CN109045224A (en)

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CN201980071685.XA CN113543795A (en) 2018-10-29 2019-01-18 Sunflower head and coix seed compound composition and application thereof in preparation of medicine for treating liver injury
PCT/CN2019/072318 WO2020087784A1 (en) 2018-10-29 2019-01-18 Sunflower head-job's tears seed compound composition and use thereof in preparing drugs for treating liver damage
AU2019100729A AU2019100729A4 (en) 2018-10-29 2019-07-03 Compound Composition of Sunflower Head and Coix Seed and Use Thereof in Treatment of Liver Injury

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Application publication date: 20181221