CN1733199A - Liver-protecting detoxification particles for curing drug induced liver injury and its production method - Google Patents
Liver-protecting detoxification particles for curing drug induced liver injury and its production method Download PDFInfo
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Abstract
Disclosed are liver-protecting detoxification particles for treating drug-induced liver injury and its production method, which consists of extracting aloe polysaccharides, Tribulus terrestris saponins and date polysaccharides, then mixing and producing granules by the proportion of the original medicament.
Description
One, technical field
The present invention relates to a kind of protecting liver and detoxication granule and production method thereof of medicine liver damage.
Two, background technology
Drug induced hepatic injury (Drug-induced Liver Injury is abbreviated as DILI) be meant because medicine or and the toxic action of metabolite, or body produces the liver injury that anaphylaxis causes to medicine.Along with the extensive use of chemical synthetic drug, DILI has become the clinical common factor that causes hepar damnification.In western countries, the 2% jaundice patient who is in hospital is caused that by medicine about 1/4 fulminant hepatic failure is relevant with medicine.The domestic literature report, the sickness rate of DILI accounts for inpatient's 1/600-1/3500.Cause the common medicine of DILI that Tri-Biocin, antitubercular agent, antineoplastic agent, cardiovascular drugs and part Chinese herbal medicine etc. are arranged.
The susceptibility of DILI is relevant with genetic polymorphism, enzyme inducer or the factors such as inhibitor and nutriture of age, sex, medicine biotransformation enzyme.Its mechanism is still very not clear, clinically also lacks effective therapeutic scheme.Research thinks, Chinese medicine has certain advantage aspect the drug induced hepatic injury preventing and treating, and therefore, actively develops the research of treatment DILI medicine aspect, further points out the intervention mechanism of its genesis mechanism and Chinese medicine, has bigger learning value and clinical guidance meaning.And along with the extensive use of chemical synthetic drug, the DILI morbidity has the trend that increases year by year.According to statistics, the medicament categories that can cause hepatic injury reaches more than 1000 kinds.Acute DILI accounts for the 4%-7% of drug side effect, even by chance fatal case can take place, and particularly is being associated with on the basis of hepatopathy easier generation DILI.The Meier Y of Switzerland Su Li university hospital etc. studies show that DILI can take place about 1.4% internal medicine inpatient.And in antituberculosis therapy, because of drug-induced liver injury accounts for 5-10%, even up to 30%.
The pathogenesis of DILI is different because of medicine, and is very complicated, in most cases it be unclear that.Some medicine has direct toxic action, generally can predict by its liver injury that causes, and infringement is relevant with drug dose, and peculiar by some drugs; Other medicines only cause hepatic injury at the individuality of sensitivity once in a while, and and dosage indifference, whether prediction takes place also to be difficult to.Along with the development of modern science, the medical worker has carried out a series of researchs to the pathogeny of DILI from different perspectives, and has obtained bigger progress.Research is thought, causes the reason of hepar damnification a lot, as virus, some chemical substance, medicine etc.These factors cause that the mechanism of hepatic injury is not quite similar, but mainly are to liver plasma membrane and mitochondrial destruction, and then cause degeneration, the necrosis of whole cell, cause a series of sings and symptomses such as transaminase's rising, jaundice, weak, poor appetite.When hepatic injury took place, damage in various degree appearred in liver plasma membrane, very then broke the part or all of film dissolving of cell; Monofilm appears being partly dissolved or becoming in mitochondrial inner membrane under the Electronic Speculum, and quantity reduces; Reticulum dilatation is irregular blister, and rough endoplasmic reticulum has the granule of taking off phenomenon.Causing of these infringements is by the coefficient result of multiple factor in the body.And liver is the important place of biotransformation and energy metabolism, after most medicines are taken in by body or are absorbed, to could get rid of external through the liver metabolism processing, liver is healthy most important for the people's, therefore, how to prevent and treat drug induced hepatic injury, and the liver of a health is arranged, being the problem that people are concerned about very much, also is the at present global severe problem that solves that urgently waits.
Three, summary of the invention
At above-mentioned situation, the present invention's purpose just provides a kind of protecting liver and detoxication granule and production method thereof of medicine liver damage, treatment problem with effective solution drug induced hepatic injury, the technical scheme of its solution is, as everybody knows, Chinese medicine and pharmacy is the treasure-house of a greatness, its resource is inexhaustible, with not to the utmost, particularly along with the deep exploitation and the research of Chinese medicine and pharmacy, the advantage of treatment by Chinese herbs more and more highlights, according to the Chinese medicine principle, said drug induced hepatic injury is from theory of Chinese medical science and clinical practice, damp and hot poison accumulates, incoordination between the liver and spleen, disorder of QI and blood, deficient vital QI leading to lingering of pathogen, simulataneous insufficiency and excessive, it is the basic pathogenesis of DILI, the removing damp-heat detoxifcation, transferring the liver spleen stomach function regulating is the fundamental law of treatment DILI, in view of the above, medicine of the present invention adopts Aloe, Fructus Tribuli and Fructus Jujubae are made, its production method is with Aloe, Fructus Tribuli and Fructus Jujubae adopt first and then unique technology to extract Aloe polysaccharide respectively, behind Fructus Tribulus total saponins and the jujube polysaccharide, remix is made granule, Aloe polysaccharide is to decoct with water after shredding piece by the fresh aloe leaf, get filtrate, get supernatant after leaving standstill, after concentrating, adding ethanol, staticly settle again, use ethanol, acetone, the ether washing promptly gets aloe coarse polysaccharid; Fructus Tribulus total saponins is to be pulverized by Fructus Tribuli to get filtrate with alcohol reflux, after concentrating, adds water again and becomes solution, uses ether defatting, uses n-butanol extraction, reclaims n-butyl alcohol and gets Fructus Tribulus total saponins; Jujube polysaccharide is to add the alcohol reflux defat after shredding piece by Fructus Jujubae, abandons filtrate, in medicinal residues, decoct with water again, filtrate, leave standstill the back and extract supernatant, reconcentration adds ethanol afterwards, leave standstill precipitate, wash again the Fructus Jujubae crude polysaccharides.Product of the present invention can be effective to the medicine liver damage, its production method novelty, uniqueness, science are that one of medicine liver damage is created greatly, and clinical meaning is huge, it is succeeded in developing to the medicine liver damage and has opened up bright prospect, must bring benefit to the mankind.
Four, the specific embodiment
Below in conjunction with practical situation the specific embodiment of the present invention is elaborated.
Provide by prescription, the present invention is by by weight: Aloe 35-45%, Fructus Tribuli 15-25% and Fructus Jujubae 35-45% make, it is preferably by by weight: Aloe 40%, Fructus Tribuli 20% and Fructus Jujubae 40% are made, specifically also can show as a dosage is to be made by Aloe 30g, Fructus Tribuli 15g and Fructus Jujubae 30g; Realize that above-mentioned medicine liver damage with the particulate production method of protecting liver and detoxication is, at first with Aloe, Fructus Tribuli and Fructus Jujubae extract respectively Aloe polysaccharide, Fructus Tribulus total saponins and jujube polysaccharide, again in primary drug weight: Aloe 35-45%, Fructus Tribuli 15-25% is mixed with Fructus Jujubae 35-45% and is in the same place, the 15g finished medicines is equivalent to crude drug 52.5g, make granule with granulator, said Aloe polysaccharide is to shred piece by fresh Folium Aloe (8kg), fries in shallow oil three times, for the first time adding 4 times of water gagings (32kg water) fried in shallow oil 2 hours, get filtrate, add 3 times of water gagings (24kg water) for the second time, fried in shallow oil 2 hours, get filtrate, add 2 times of water gagings (16kg water) for the 3rd time and fried in shallow oil 1 hour, get filtrate, merge three times filtrate, left standstill 12 hours, extract supernatant, residue is centrifugal, centrifugal liquid and supernatant merge filtrate only, be concentrated into about 1000ml, slowly add 95% ethanol again, make to contain alcohol amount and reach 80%, left standstill 12 hours, the ethanol that inclines liquid gets precipitate, uses ethanol more respectively, acetone, get aloe coarse polysaccharid after the ether washing; Said Fructus Tribulus total saponins is to add 75% alcohol reflux 3 times after being pulverized by Fructus Tribuli 500g, merge three times filtrate, reclaim ethanol again, the concentrated solution (thing) after it is refluxed does not have the alcohol flavor, adds water again and becomes solution (water can not add too much, get final product on a small quantity), solution is used ether 500ml, 300ml, 200ml defat 3 times respectively, discards, and filtrate extracts 3 times with n-butyl alcohol 500ml, 500ml, the 400ml of water saturation respectively, merge three times n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol gets Fructus Tribulus total saponins again; Said jujube polysaccharide is to be shredded by Fructus Jujubae 1000g, with alcohol reflux defat 2 times, filter, get filtrate, medicinal residues decocting again boil 3 times, for the first time adding 10 times of water gagings (10000g water) fried in shallow oil 2.5 hours, filter solution, for the second time add 8 times of amounts of water (8000g water), fried in shallow oil 2 hours, filter to get filtrate, add 6 times of water gagings (6000g water) for the third time and fried in shallow oil 2 hours, filter, get filtrate, merge three times filtrate, left standstill 12 hours, and extracted supernatant, residue centrifugal centrifugal liquid and supernatant merging, reconcentration is to about 800ml, slowly add 95% ethanol in the concentrated solution, make it ethanol content, left standstill 12 hours 80%, the ethanol that inclines gets precipitate, uses ethanol more respectively, acetone, ether wash jujube polysaccharide.
The granule that realization is made by Aloe 40%, Fructus Tribuli 20% and the Fructus Jujubae 40% of weight meter, its production method is the same, as long as with Aloe 35-45% change 40% into, Fructus Tribuli 15-25% changes 20% into, Fructus Jujubae 35-45% changes 40% into and gets final product; The granule of the present invention that realization is made by Aloe 30g, Fructus Tribuli 15g and Fructus Jujubae 30g, its method is as long as make Aloe 40%, Fructus Tribuli 20%, Fructus Jujubae 40% into Aloe 30g, Fructus Tribuli 15g and Fructus Jujubae 30g respectively, after will preparing Aloe polysaccharide, Fructus Tribulus total saponins and jujube polysaccharide as stated above again, carry out mixing granulation with the compatibility ratio of primary medicine Aloe 30g, Fructus Tribuli 15g and Fructus Jujubae 30g and get final product, so repeat no longer one by one.Be equivalent to primary medicine 10g approximately at the above-mentioned finished product Chinese medicinal granule 1g that makes.
Aloe bitter cold in the side, go into liver, the heart, spleen channel, the cool liver of function heat clearing away, the detoxifcation relieving constipation, its " cold can heat extraction; the hardship dampness of purging heat ... main hot blast unhappiness; steam between the breast side of body " (" Bencao Jingshu "), " all genus livers be disease, and hot person is arranged; that uses must be undoubtedly also " (" the book on Chinese herbal medicine remittance is sayed ") is so be monarch drug; Fructus Tribuli toil and temperature is gone into liver, lung meridian, the promoting the circulation of blood of the function therapeutic method to keep the adverse QI flowing downwards, " QI invigorating is reduced phlegm, the wet dissipation removing blood stasis for town's liver-wind, removing fire from the liver " (" book on Chinese herbal medicine is new again ") helps Aloe liver heat removing dehumidifying first, QI and blood regulating second, regulating the liver and spleen; The sweet temperature of Fructus Jujubae is gone into the taste warp, function " spleen reinforcing stomach function regulating, supplementing QI for promoting the production of body fluid transfer battalion to defend; to separate poison of drug " (" Chinese medicine voluminous dictionary "), " main trusted subordinate's pathogen, regulating the spleen and stomach is supported spleen, helps 12 warps ... and hundred medicines " (" legendary god of farming's BAICAO warp "), two medicines share, depressed liver-energy dispersing and QI regulating, and the stomach function regulating spleen invigorating is ministerial drug altogether; Fructus Jujubae again can " with hundred medicines ", " separating poison of drug ", is to make it agent for assistant.
By above-mentioned situation as can be known, granule of the present invention has the dry temperature of heat clearing away, removing heat in the liver for detoxication, depressed liver-energy dispersing and QI regulating, invigorating the spleen and regulating the stomach, and medicine liver damage just in time, and clinical practice and zoopery have also proved this particulate useful effect fully, physical resource is as follows:
One, clinical data
1, selects the case standard
All sides of body that causes because of medication expand or pain, nausea and vomiting or the jaundice of body order or heating, vexed xerostomia, stool is smooth, tongue is dark red, yellow and greasy fur, stringy and rolling pulse or number is gone to a doctor and inpatient as the standard of selecting case.
2, diagnostic criteria
According to the Chinese medicine pathogeny, all to have because of taking the clinical manifestation that medicine causes be dampness-heat in the liver and gallbladder, liver spleen (stomach) discord, qi depression to blood stasis, deficiecny of liver-YIN, and above-mentioned (1) described symptom is arranged, be diagnosed as drug induced hepatic injury.
3, therapeutic scheme
Every day oral granule of the present invention, every day secondary, each 1 time sooner or later, each 3.5g (being equivalent to crude drug 37g) serve on 20 days, observe the curative effect.
4, efficacy assessment standard
Recovery from illness: the symptom complete obiteration, and all normal through blood check liver function indexes.
Effectively: symptom takes an evident turn for the better, and blood examination part liver function indexes is normal.
Invalid: symptom does not have any improvement, even the trend of increasing the weight of is arranged.
5, statistical disposition
By above-mentioned standard and therapeutic scheme 46 people are carried out drug induced hepatic injury in clinical and treat, wherein male 30 people, women 16 people, statistical result such as following table:
Table 1
| The example number | Recovery from illness | Effectively | Invalid | Total effective rate |
| 46 | 28 | 15 | 3 | 93％ |
And in clinical application acomia incumbent what new ill symptoms, safe and effective.
6, conclusion
Shown that by above-mentioned situation drug particles of the present invention is obvious to medicine liver damage effect, curative effect has outstanding clinical value (meaning) up to more than 93%.
Two, animal model experiment situation
For guaranteeing the hepatoprotective effect of medicine of the present invention, the applicant has also made a large amount of animal model experiments, and relevant situation is as follows:
1, laboratory animal
180 of regular grade Kunming mouses, male and female half and half, body weight 18-22 gram, available from Henan Province's Experimental Animal Center, credit number: 410115.Feed in Henan College Of Traditional Chinese Medicine zoopery center with common Mus material, Mus is expected available from Henan Province's Experimental Animal Center; Credit number: 4104041.
2, animal group technology
180 of Kunming mouses are divided into tripterygium glycosides modeling group (60), isoniazid modeling group (60) and tetracycline modeling group (60) at random.Each modeling group is respectively model group again, large, medium and small 3 the dosage groups of protecting liver and detoxication granule administration, diammonium glycyrrhizinate matched group and blank group, 10 every group.
3, medication
The large, medium and small dosage group of mice is pressed the 0.2ml/10g body weight and is irritated stomach with the heavy dose of 21.6g/kg of protecting liver and detoxication granule, middle dosage 10.8g/kg, low dose of 5.4g/kg respectively before the modeling, the diammonium glycyrrhizinate matched group is pressed the 0.2ml/10g body weight with 75mg/kg and is irritated stomach, every day 1 time, continuous 5 days.Fasting 12h began modeling after the 5th was irritated stomach, and difference fasting (can't help water) is 16 hours before putting to death.Model group and blank group are given isopyknic normal saline respectively and are irritated stomach.
Tripterygium glycosides modeling group, isoniazid modeling group, tetracycline modeling group are mixed with suspension by the dosage of 0.270g/kg, 0.180g/kg, 2.25g/kg respectively, press the 0.2ml/10g body weight and irritate 1 modeling of stomach.The blank group gives isopyknic normal saline and irritates stomach.
4, sample preparations method
Mice is plucked eyeball and gets blood, and 3000rpm is centrifugal, and preparation serum is standby; Dislocation is put to death then, takes out liver organization and weighs; Get 1 of same position hepatic tissue, it is fixing to put into 10% formalin, and PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM is done in the preparation section; Get 1 of same position hepatic tissue, it is fixing to put into 25% glutaraldehyde solution, and electron microscopic observation is done in the preparation section.
5, index detection method
Serum alanine aminotransferase (ALT), aspartate amino transferase (AST): adopt the SABAPM4000 automatic clinical chemistry analyzer to detect.
Serum superoxide dismutases (SOD): adopt xanthine oxidase to measure.
Serum malonaldehyde (MDA): adopt thiobarbituricacid (TBA) method to measure.
Serum glutathion peroxidase (GSH-PX) vigor: adopt chemical colorimetry to measure.
Serum il-18: adopt the ELASA method to measure.
The hepatic tissue pathology morphological observation: murine liver tissue is observed under the OLYMPUS optical microscope through fixing, dehydration, waxdip, embedding, section, dewaxing, HE dyeing, dehydration, transparent, mounting.
The hepatic tissue cell Ultrastructural observation: the Electronic Speculum pathological section adopts uranium acetate and lead citrate dyeing, the H-7500 of Hitachi transmission electron microscope observation.
Hepatocellular apoptosis: adopt biotin dutp otch end labelling (TUNEL) method of terminal deoxynucleotidyl transferase mediation to detect.
6, statistical procedures
Use the SPSS11.5 statistical software experimental data is carried out statistical analysis, enumeration data adopts one factor analysis of variance, and measurement data adopts Ridit to analyze.All results directly export by microcomputer.
The protecting liver and detoxication granule is to the influence of acute liver damage mice ALT, AST due to the tripterygium glycosides (x ± s)
| Group | n | Dosage (g.kg -1) | ALT(U.L -1) | AST(U.L -1) |
| Dosage group small dose group in the heavy dose of group of blank group model group diammonium glycyrrhizinate group | 10 10 10 10 10 10 | Equal-volume equal-volume 0.075 21.6 10.8 5.40 | 32.3±7.76* 98.3±13.01* 65.7±12.74* 53.1±12.91* 61.5±12.41* 61.2±10.16* | 37.1±6.05* 96.3±13.86 47.8±11.05* 45.5±9.59* 46.6±8.47* 53.5±10.95* |
Annotate: * represents to compare P＜0.05 with model group
Above-mentioned each the dosage group of protecting liver and detoxication granule that shows all can effectively reduce Serum ALT, AST, with model group significant statistical significance (P＜0.05) is arranged relatively.
The protecting liver and detoxication granule is to the influence of acute liver damage mice ALT, AST due to the isoniazid (x ± s)
| Group | n | Dosage (g.kg -1) | ALT(U.L -1) | AST(U.L -1) |
| Dosage group small dose group in the heavy dose of group of blank group model group diammonium glycyrrhizinate group | 10 10 10 10 10 10 | Equal-volume equal-volume 0.075 21.6 10.8 5.40 | 32.3±7.76* 104.3±14.24 53.5±8.18* 40.7±8.21* 47.5±10.93* 49.9±8.94* | 37.1±6.06* 106.5±13.80 52.5±8.50* 46.1±9.67* 51.8±9.67* 53.5±9.35* |
Annotate: * represents to compare P＜0.05 with model group
Each dosage group of protecting liver and detoxication granule all can effectively reduce Serum ALT, AST, with model group significant statistical significance (P＜0.05) is arranged relatively.Wherein best with the heavy dose of group of protecting liver and detoxication granule effect especially.
The protecting liver and detoxication granule is to the influence of acute liver damage mice ALT, AST due to the tetracycline (x ± s)
| Group | n | Dosage (g.kg -1) | ALT(U.L -1) | AST(U.L -1) |
| Dosage group small dose group in the heavy dose of group of blank group model group diammonium glycyrrhizinate group | 10 10 10 10 10 10 | Equal-volume equal-volume 0.075 21.6 10.8 5.40 | 32.3±7.76* 91.2±12.62 43.6±9.89* 36.1±6.38* 39.2±9.04* 38.6±9.11* | 37.1±6.05* 95.1±15.91 58.1±11.31* 47.1±7.80* 53.8±7.44* 61.6±11.22* |
Annotate: * represents to compare P＜0.05 with model group
As can be seen from the above table, tetracycline model group mice serum ALT, AST obviously raise, and relatively having with the blank group significantly has statistical significance (P＜0.05), and be wherein best with the heavy dose of group of protecting liver and detoxication granule effect especially.
The protecting liver and detoxication granule is to the influence of acute liver damage SOD in Mice, MDA, GSH-PX due to the tripterygium glycosides (x ± s)
| Group | n | Dosage (g.kg -1) | SOD(U.ml -1) | MDA (OD value) | GSH-PX(μmol.L -1) |
| Dosage group small dose group in the heavy dose of group of blank group model group diammonium glycyrrhizinate group | 10 10 10 10 10 10 | Equal-volume equal-volume 0.075 21.6 10.8 5.40 | 114.76±13.11* 63.73±11.66 67.15±15.25 87.02±19.07* 76.31±14.03 58.64±18.64 | 0.152± 0.029* 0.223±0.034 0.176± 0.020* 0.159± 0.024* 0.166± 0.021* 0.179± 0.018* | 1079.83±114.52* 765.73±138.41 1005.21±204.12* 1228.91±195.19* 1418.03±164.06* 1044.83±253.20* |
Annotate: * represents to compare P＜0.05 with model group.
As can be seen from the above table, the heavy dose of group of protecting liver and detoxication granule can significantly improve SOD in serum and GSH-PX level, reduce the serum MDA level, in, low dose and diammonium glycyrrhizinate group become and can obviously improve serum GSH-PX level, reduce the MDA level, significant statistical significance (P＜0.05) is more all arranged with model group.Improve GSH-PX horizontal aspect, the effect of big or middle dosage group obviously is better than diammonium glycyrrhizinate group (P＜0.05).
The protecting liver and detoxication granule to the influence of acute liver damage mice IL-18 (x ± s, n=10)
| Group | Dosage (g.kg -1) | IL-18(pg.ml -1) | ||
| The Radix Tripterygii Wilfordii group | The isoniazid group | The tetracycline group | ||
| Dosage group small dose group in the heavy dose of group of blank group model group diammonium glycyrrhizinate group | Equal-volume equal-volume 0.075 21.6 10.8 5.40 | 23.96±4.07* 34.36±6.26 30.06±9.97 29.67±6.47 24.32±5.84* 23.65±6.83* | 23.96±4.07 17.79±3.88 18.07±5.25 19.65±6.89 18.26±6.09 20.32±5.77 | 23.96±4.07* 40.99±6.24 30.28±9.98* 26.16±7.31* 28.4±10.12* 28.60±6.49* |
Annotate: * represents to compare P＜0.05 with model group.
As can be seen from the above table, in the protecting liver and detoxication granule, small dose group can make the LI-18 level obviously reduce, with model group significant statistical significance (P＜0.05) is arranged relatively, each dosage of protecting liver and detoxication granule and diammonium glycyrrhizinate group all can make the LI-18 level obviously reduce, and with model group significant statistical significance (P＜0.05) are arranged relatively.
The protecting liver and detoxication granule is to the influence of acute liver damage SOD in Mice, MDA, GSH-PX due to the isoniazid (x ± s)
| Group | n | Dosage (g.kg -1) | SOD(U.ml -1) | MDA (OD value) | GSH-PX(μmol.L -1) |
| Dosage group small dose group in the heavy dose of group of blank group model group diammonium glycyrrhizinate group | 10 10 10 10 10 10 | Equal-volume equal-volume 0.075 21.6 10.8 5.40 | 114.76±13.11* 36.56±11.59 53.78±9.10* 47.95±6.64 50.64±11.56 43.04±11.44 | 0.152± 0.029* 0.211±0.027 0.168± 0.020* 0.174±0.026 0.170± 0.030* 0.175±0.031 | 1079.83±114.52* 844.47±99.31 1081.54±173.80* 1126.41±141.85* 1075.08±145.30* 1037.08±151.65* |
Annotate: * represents to compare P＜0.05 with model group.
As can be seen from the above table, the large and small dosage group of protecting liver and detoxication granule can significantly improve serum GMH-PX level, and middle dosage group can significantly improve serum GSH-PX level, reduces the MDA level, with model group significant statistical significance (P＜0.05) is arranged more all.
The protecting liver and detoxication granule is to the influence of dissimilar DILI mouse liver cell apoptosis
By each group (blank group, model group, positive controls, large, medium and small dose of group) of various DILI (Radix Tripterygii Wilfordii group, isoniazid group, tetracycline group) mouse experiment is carried out specific stain, the apoptosis hepatocyte shows brown xanchromatic endochylema or cell.Observation statistical result is shown in the following table.
According to what of observed apoptotic body number in the same visual field, being divided into is four groups.Standard is as follows:
-: hepatocyte does not have apoptotic body person.
+: in the same visual field of hepatocyte, observe 1 apoptotic body person.
++; In the same visual field of hepatocyte, observe 2-4 apoptotic body person.
+++: observed the apoptotic body person that (contains 5) more than 5 in the same visual field of hepatocyte.
Hepatocellular apoptosis corpusculum observed result (unit: only) is respectively organized in the hepatic injury experiment due to the Radix Tripterygii Wilfordii
| Group | n | - | + | ++ | +++ |
| Dosage group small dose group in the heavy dose of group of blank group model group diammonium glycyrrhizinate group | 10 10 10 10 10 10 | 9 0 10 10 10 2 | 1 1 0 0 0 1 | 0 2 0 0 0 7 | 0 7 0 0 0 0 |
As can be seen from the above table, blank group mouse liver cell apoptosis degree is slight; Tripterygium glycosides model group mouse liver cell apoptosis degree is serious, analyzes through Ridit, with the blank group significant statistical significance (P＜0.05) is arranged relatively; Each dosage of protecting liver and detoxication granule and diammonium glycyrrhizinate group mouse liver cell apoptosis degree all alleviate to some extent, and wherein especially with big or middle dosage and diammonium glycyrrhizinate group best results, Ridit analyzes, and with model group significant statistical significance (P＜0.05) is arranged relatively.
Respectively organize mouse liver cell by the experiment of DILI due to tetracycline and observe, record the statistical result of apoptotic body, see the following form:
Hepatocellular apoptosis corpusculum observed result (unit: only) is respectively organized in the hepatic injury experiment due to the tetracycline
| Group | n | - | + | ++ | +++ |
| Dosage group small dose group in the heavy dose of group of blank group model group diammonium glycyrrhizinate group | 10 10 10 10 10 10 | 9 1 9 2 1 10 | 1 4 1 2 5 0 | 0 4 0 1 4 0 | 0 1 0 5 0 0 |
As can be seen from the table, blank group mouse liver cell apoptosis degree is slight; Tetracycline model group mouse liver cell apoptosis degree is serious, analyze through Ridit, with the blank group significant statistical significance (P＜0.05) is arranged relatively: protecting liver and detoxication granule small dose group and diammonium glycyrrhizinate group mouse liver cell apoptosis degree obviously alleviate, analyze through Ridit, significant statistical significance (P＜0.05) is relatively arranged with model group.
In a word, show by above-mentioned situation, the basic pathogenesis that damp and hot poison accumulates, incoordination between the liver and spleen is DILI, removing damp-heat detoxifcation, accent liver spleen stomach function regulating are the fundamental laws of treatment DILI.The protecting liver and detoxication granule has the effect of heat clearing and damp drying, removing heat in the liver for detoxication, depressed liver-energy dispersing and QI regulating, invigorating the spleen and regulating the stomach, it is the effective Chinese medicine preparation of control DILI, can effectively reduce dissimilar DILI mice serum ALT, AST, remarkable rising SOD in serum and GSH-PX level, reduce the MDA level, obviously reduce serum il-18 level, hepatocyte injury, apoptosis regulating liver-QI changes of cell ultrastructure are improved.Have bigger learning value and clinical practice meaning, for the treatment by Chinese herbs drug induced hepatic injury has been opened up new bright prospect.
Claims (6)
1, a kind of protecting liver and detoxication granule of medicine liver damage is characterized in that, by by weight: Aloe 35-45%, Fructus Tribuli 15-25% and Fructus Jujubae 35-45% make.
2, the protecting liver and detoxication granule of medicine liver damage according to claim 1 is characterized in that it being by said, and Aloe 40%, Fructus Tribuli 20% and Fructus Jujubae 40% are made.
3, the protecting liver and detoxication granule of medicine liver damage according to claim 1 and 2 is characterized in that it being to be made by said Aloe 30g, Fructus Tribuli 15g and Fructus Jujubae 30g.
4, realize the particulate production method of protecting liver and detoxication of the said medicine liver damage of claim 1, it is characterized in that being, at first with Aloe, Fructus Tribuli and Fructus Jujubae extract respectively Aloe polysaccharide, Fructus Tribulus total saponins and jujube polysaccharide, again in primary drug weight: Aloe 35-45%, Fructus Tribuli 15-25% is mixed with Fructus Jujubae 35-45% and is in the same place, and the 15g finished medicines is equivalent to crude drug 52.5g, makes granule with granulator, said Aloe polysaccharide is to shred piece by fresh Folium Aloe 8000g, fry in shallow oil three times, add 4 times of water gagings for the first time and fried in shallow oil 2 hours, get filtrate, add for the second time 3 times of water gagings, fried in shallow oil 2 hours, filtrate, add 2 times of water gagings and fried in shallow oil 1 hour for the 3rd time, get filtrate, merge three times filtrate, left standstill 12 hours, extract supernatant, residue is centrifugal, centrifugal liquid and supernatant merge clean filtrate, be concentrated into about 1000ml, slowly add 95% ethanol again, make and contain alcohol amount and reach 80%, left standstill 12 hours, the ethanol that inclines liquid gets precipitate, uses ethanol more respectively, acetone, get aloe coarse polysaccharid after the ether washing; Said Fructus Tribulus total saponins is to add 75% alcohol reflux 3 times after being pulverized by Fructus Tribuli 500g, merge three times filtrate, reclaim ethanol again, concentrated solution after it is refluxed does not have the alcohol flavor, adds water again and becomes solution, and solution is used ether 500ml, 300ml, 200ml defat 3 times respectively, discard, filtrate extracts 3 times with n-butyl alcohol 500ml, 500ml, the 400ml of water saturation respectively, merges three times n-butyl alcohol liquid, and the reclaim under reduced pressure n-butyl alcohol gets Fructus Tribulus total saponins again; Said jujube polysaccharide is to be shredded by Fructus Jujubae 1000g, with alcohol reflux defat 2 times, filters, get filtrate, medicinal residues decocting again boil 3 times, add 10 times of water gagings for the first time and fry in shallow oil 2.5 hours, filter solution, for the second time add 8 times of amounts of water, fried in shallow oil 2 hours, filter to get filtrate, add 6 times of water gagings for the third time and fried in shallow oil 2 hours, filter, get filtrate, merge three times filtrate, left standstill 12 hours, and extracted supernatant, residue centrifugal centrifugal liquid and supernatant merging, reconcentration is to about 800ml, slowly add 95% ethanol in the concentrated solution, make it ethanol content, left standstill 12 hours 80%, the ethanol that inclines gets precipitate, uses ethanol more respectively, acetone, ether wash jujube polysaccharide.
5, the particulate production method of the protecting liver and detoxication of medicine liver damage according to claim 4; it is characterized in that being; at first Aloe, Fructus Tribuli and Fructus Jujubae are extracted respectively Aloe polysaccharide, Fructus Tribulus total saponins and jujube polysaccharide; again in weight percent: the crude drug in whole ratio of Aloe 40%, Fructus Tribuli 20% and Fructus Jujubae 40% is mixed and is in the same place; cause grain with granulator, the 15g finished medicines is equivalent to crude drug 52.5g.
6, the particulate production method of the protecting liver and detoxication of medicine liver damage according to claim 4; it is characterized in that being; at first Aloe, Fructus Tribuli and Fructus Jujubae are extracted respectively Aloe polysaccharide, Fructus Tribulus total saponins and jujube polysaccharide; be mixed with the crude drug in whole ratio of Aloe 30g, Fructus Tribuli 15g and Fructus Jujubae 30g again and be in the same place; cause grain with granulator, the 15g finished medicines is equivalent to crude drug 52.5g.
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| CNB2005100179277A CN1325097C (en) | 2005-08-26 | 2005-08-26 | Liver-protecting detoxification particles for curing drug induced liver injury and its production method |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105311067A (en) * | 2014-07-29 | 2016-02-10 | 西安旭煌生物技术有限公司 | Method for extracting total tribulus terrestris saponins from stems and leaves of tribulus terrestris |
| CN108339051A (en) * | 2018-05-03 | 2018-07-31 | 云南彝山天宝生物医药有限公司 | A kind of drug that treating chemical damage, preparation method and applications |
| CN109315647A (en) * | 2018-09-30 | 2019-02-12 | 江南大学 | A kind of composite aloe alcohol-dissolving liver-protecting drink and preparation method thereof |
-
2005
- 2005-08-26 CN CNB2005100179277A patent/CN1325097C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105311067A (en) * | 2014-07-29 | 2016-02-10 | 西安旭煌生物技术有限公司 | Method for extracting total tribulus terrestris saponins from stems and leaves of tribulus terrestris |
| CN108339051A (en) * | 2018-05-03 | 2018-07-31 | 云南彝山天宝生物医药有限公司 | A kind of drug that treating chemical damage, preparation method and applications |
| CN109315647A (en) * | 2018-09-30 | 2019-02-12 | 江南大学 | A kind of composite aloe alcohol-dissolving liver-protecting drink and preparation method thereof |
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| Publication number | Publication date |
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| CN1325097C (en) | 2007-07-11 |
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