CN105998138A - Application of Hugan Buzure particles in preparing medicine for treating drug induced liver injury - Google Patents

Application of Hugan Buzure particles in preparing medicine for treating drug induced liver injury Download PDF

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Publication number
CN105998138A
CN105998138A CN201610378270.5A CN201610378270A CN105998138A CN 105998138 A CN105998138 A CN 105998138A CN 201610378270 A CN201610378270 A CN 201610378270A CN 105998138 A CN105998138 A CN 105998138A
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weight portion
zure
hepatoprotective
granule
root
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Inventor
王学海
尹强
许勇
尹海龙
马璇
穆丹丹
田芳
宋菲
周琴
黄璐
刘腊才
努尔拉江·帕合尔丁
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Ren Fu Pharmaceutical Group Stock Co
XINJIANG UIGUR PHARMACEUTICAL CO Ltd
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Ren Fu Pharmaceutical Group Stock Co
XINJIANG UIGUR PHARMACEUTICAL CO Ltd
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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)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • 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)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/235Foeniculum (fennel)
    • 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)
    • A61K36/39Convolvulaceae (Morning-glory family), e.g. bindweed
    • 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)
    • A61K36/43Cuscutaceae (Dodder family), e.g. Cuscuta epithymum or greater dodder

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
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  • Botany (AREA)
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  • Medicinal Chemistry (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses Hugan Buzure particles. The Hugan Buzure particles consist of celery seeds, seeds of cichorium inrybus L, seeds of Chinese dodder, celery roots, fennel roots and barks, roots of cichorium inrybus L and fructus foeniculi; and the Hugan Buzure particles can be used for treating drug induced liver injury. The Hugan Buzure particles not only has a good effect on treating the drug induced liver injury but also is capable of treating liver cold, stomachache, spleen retention and hypochondriac pain, joint and bone pains, rheumatism and diseases of urinary system.

Description

The application in preparation treatment drug induccd liver injury medicament of the hepatoprotective Bu Zure granule
Technical field
The present invention relates to the field of Chinese medicines, in particular it relates to hepatoprotective Bu Zure granule and preparation treatment drug induccd liver injury medicament In application.
Background technology
Drug induccd hepatic injury (drug induced liver injury, DILI) be patient during carrying out Drug therapy, due to medicine Toxicity that thing self is had and patient's anaphylaxis caused patient liver damage to medicine.Easily cause liver vessel to damage, Liver cirrhosis, induces the diseases such as hepatocarcinoma, it has also become common severe drug untoward reaction.
Adding up according to World Health Organization (WHO) (WHO), drug induced hepatic injury has risen to the 5th of the whole world cause of death, in China Medicamentous liver lesion patient accounts for the 10% of acute hepatitis inpatient, accounts for old cadre patient more than 20%, accounts in American-European countries The 30%-40% of acute hepatic failure patient.Drug induccd hepatic injury become in most drug therapeutic process common concurrently One of disease.Therefore, the medicine for the treatment of drug induccd hepatic injury needs to be studied further.
Summary of the invention
It is contemplated that at least solve one of technical problem present in prior art.To this end, it is an object of the present invention to carry Go out the medicine of a kind of effective treatment drug induccd hepatic injury.
It should be noted that the present invention is following work based on inventor and completes:
The health of the drug induccd hepatic injury serious threat mankind.Drug induced hepatic injury pathogenesis relate to organelle damage, Apoptosis, necrocytosis, ionic equilibrium are destroyed and a series of immunoreation activation process, are not independently to deposit between various mechanism , mutual asks close contact.Drug induccd hepatic injury is not only present in making of Western medicine, part Chinese medicine and health product Cause drug induccd hepatic injury with being likely to.Along with the development of medicine and pharmacology, increasing newtype drug is used for clinical treatment, medicine source The sickness rate of property hepatic injury is also in the trend risen year by year.
Hepatoprotective Bu Zure granule is tradition dimension medicine, and in side, seed of Herba Apii graveolentis character is xeothermic, can eliminate cold-damp impatency, Sal Nitri pain relieving, be in harmonious proportion Hundred medicines;Seed of Herba Cichorii Intybi character is dry cold, opens liver resistance, heat clearing and inflammation relieving, eliminates jaundice, diuresis detumescent, cures mainly liver and blocks, damp and hot Property hepatitis, icterohepatitis, anasarca etc.;Semen Cuscutae is xeothermic;Root of Herba Apii graveolentis character is xeothermic;Root bark of Foeniculum vulgare Mill. character is xeothermic, Can be dissipated cold, the kidney warming warming the stomach, water flowing dampness removing, reducing swelling and alleviating pain;Root of Herba Cichorii character is raw, and the raw humidogene of function is trembled with fear, dysregulation Bile matter, reduces liver-fire, the heat of clearing stomach, dispels jaundice, diuresis detumescent, cure mainly xeothermic property or bile matter disease;Fructus Foeniculi Can dispersing cold for relieving pain.Full side compatibility is rigorous, and burden of liver is little.
Article " hepatoprotective Bu Zure granule novel technology for extracting and the research to mouse liver injury protective effect thereof " discloses hepatoprotective cloth The effect to immunologic liver injury of ancestral's hot granule, though immunologic liver injury and drug induccd hepatic injury exist certain in clinical symptoms Relatedness, but the pathogenesis of the two is different, belongs to different indications, and therefore, it is right to distinguish in research and therapeutic process Treat.And for liver-cold, stomachache, spleen resistance hypochondriac pain and joint osteodynia, rheumatism, urinary system described in hepatoprotective Bu Zure granule description Systemic disease, wherein drug induccd hepatic injury and its function cure mainly described in disease belong to different concepts, therefore, in research with control Should treat with a certain discrimination during treatment.Inventor have studied the drug induccd treating liver injury effect of a large amount of hepatic, in research repeatedly It was unexpectedly observed that hepatoprotective Bu Zure granule can alleviate liver, the renomegaly that drug induccd hepatic injury causes, animal effectively in comparison Experimental Mortality is less, and safety is high, and significantly reduces Serum ALT, AST, recovers hepatic tissue MDA, SOD, GSH-PX, Significantly reduce the mortality rate of drug induccd hepatic injury, drug induccd hepatic injury is had good therapeutic effect, and, this hepatoprotective Bu Zure Grain structure is rigorous, and burden of liver is little, and toxic and side effects is little, can be effectively prevented from the further damage over the course for the treatment of to liver Wound.
Thus, according to an aspect of the present invention, the invention provides a kind of hepatoprotective Bu Zure granule.Enforcement according to the present invention Example, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis, seed of Herba Cichorii Intybi, Semen Cuscutae, root of Herba Apii graveolentis, root bark of Foeniculum vulgare Mill., root of Herba Cichorii, little Fructus Foeniculi, described hepatoprotective Bu Zure granule is used for treating drug induccd hepatic injury.
Hepatoprotective Bu Zure granule can alleviate liver, the renomegaly that drug induccd hepatic injury causes effectively, and zoopery mortality rate is less, Safety is high, and significantly reduces Serum ALT, AST, recovers hepatic tissue MDA, SOD, GSH-PX, significantly reduces medicine The mortality rate of source property hepatic injury, has good therapeutic effect to drug induccd hepatic injury, and, the letter of this hepatoprotective Bu Zure particulate component When, burden of liver is little, and toxic and side effects is little, can be effectively prevented from the further damage over the course for the treatment of to liver.
It addition, hepatoprotective Bu Zure granule according to the above embodiment of the present invention, it is also possible to have a following additional technical characteristic:
According to embodiments of the invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 50-150 weight portion, seed of Herba Cichorii Intybi 150-250 Weight portion, Semen Cuscutae 20-100 weight portion, root of Herba Apii graveolentis 150-250 weight portion, root bark of Foeniculum vulgare Mill. 150-250 weight portion, root of Herba Cichorii 50-150 weight portion, Fructus Foeniculi 50-150 weight portion.
According to some currently preferred embodiments of the present invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 106 weight portion, seed of Herba Cichorii Intybi 212 weight portions, Semen Cuscutae 53 weight portion, root of Herba Apii graveolentis 212 weight portion, root bark of Foeniculum vulgare Mill. 212 weight portion, root of Herba Cichorii 106 weight Amount part, Fructus Foeniculi 106 weight portion.Thus, of a tightly knit structure, burden of liver is little, and toxic and side effects is little, to drug induccd hepatic injury Therapeutic effect is more preferably.
According to embodiments of the invention, the dosage form of described hepatoprotective Bu Zure granule be selected from mixture, injection, tablet, granule, One of syrup, capsule, oral liquid, aerosol and spray.Thus, it is simple to different according to being administered object, difference is used Dosage form.
According to embodiments of the invention, described hepatoprotective Bu Zure granule provides with the form of hepatoprotective Bu Zure granule.Thus, profit Use existing Chinese patent medicine, drug induccd hepatic injury can be treated, and, the good effect of medicine, toxic and side effects is little.
According to another aspect of the invention, present invention also offers aforesaid hepatoprotective Bu Zure granule purposes in preparing medicine. According to embodiments of the invention, described medicine is used for treating drug induccd hepatic injury, and wherein, described hepatoprotective Bu Zure granule comprises: Seed of Herba Apii graveolentis, seed of Herba Cichorii Intybi, Semen Cuscutae, root of Herba Apii graveolentis, root bark of Foeniculum vulgare Mill., root of Herba Cichorii, Fructus Foeniculi.
According to embodiments of the invention, hepatoprotective Bu Zure granule can alleviate liver, the renomegaly that drug induccd hepatic injury causes effectively, Zoopery mortality rate is less, and safety is high, and significantly reduces Serum ALT, AST, recover hepatic tissue MDA, SOD, GSH-PX, significantly reduces the mortality rate of drug induccd hepatic injury, has good therapeutic effect to drug induccd hepatic injury, and, should Hepatoprotective Bu Zure particulate component letter is worked as, and burden of liver is little, and toxic and side effects is little, can be effectively prevented from over the course for the treatment of to liver Further damage.
According to embodiments of the invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis, seed of Herba Cichorii Intybi, Semen Cuscutae, root of Herba Apii graveolentis, Root bark of Foeniculum vulgare Mill., root of Herba Cichorii, Fructus Foeniculi.
According to embodiments of the invention, the dosage form of described medicine is selected from mixture, injection, tablet, granule, syrup, glue One of capsule, oral liquid, aerosol and spray.Thus, it is simple to different according to being administered object, different dosage forms is used.
According to embodiments of the invention, described medicine provides with the form of hepatoprotective Bu Zure granule.Thus, existing middle one-tenth is utilized Medicine, can treat drug induccd hepatic injury, and the good effect of medicine, and toxic and side effects is little.
The additional aspect of the present invention and advantage will part be given in the following description, and part will become bright from the following description Aobvious, or recognized by the practice of the present invention.
Accompanying drawing explanation
Above-mentioned and/or the additional aspect of the present invention and advantage the accompanying drawings below description to embodiment will be apparent from from combining and Easy to understand, wherein:
Fig. 1 shows that in the experiment of drug induccd hepatic injury according to an embodiment of the invention, each experimental group hepatic tissue section HE contaminates Chromatic graph sheet, wherein, A is blank group, and B is model group, and C is model+compound liver-benepitino remedy granule group, and D is model+liver Refreshing granule group, E is model+hepatoprotective Bu Zure granule (32ml/kg) group, and F is model+hepatoprotective Bu Zure granule (16ml/kg) Group, G is model+hepatoprotective Bu Zure granule 8ml/kg group.
Detailed description of the invention
Embodiments of the invention are described below in detail.The embodiments described below is exemplary, is only used for explaining the present invention, and It is not considered as limiting the invention.
According to an aspect of the present invention, the invention provides a kind of hepatoprotective Bu Zure granule, according to embodiments of the invention, should Hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis, seed of Herba Cichorii Intybi, Semen Cuscutae, root of Herba Apii graveolentis, root bark of Foeniculum vulgare Mill., root of Herba Cichorii, Fructus Foeniculi.And And, this hepatoprotective Bu Zure granule is used for treating drug induccd hepatic injury.
Inventor has surprisingly found that, hepatoprotective Bu Zure granule can alleviate liver, the renomegaly that drug induccd hepatic injury causes effectively, Zoopery mortality rate is less, and safety is high, and significantly reduces Serum ALT, AST, recover hepatic tissue MDA, SOD, GSH-PX, significantly reduces the mortality rate of drug induccd hepatic injury, has good therapeutic effect to drug induccd hepatic injury, and, should Hepatoprotective Bu Zure particulate component letter is worked as, and burden of liver is little, and toxic and side effects is little, can be effectively prevented from over the course for the treatment of to liver Further damage.
According to a particular embodiment of the invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 50-150 weight portion, seed of Herba Cichorii Intybi 150-250 weight portion, Semen Cuscutae 20-100 weight portion, root of Herba Apii graveolentis 150-250 weight portion, root bark of Foeniculum vulgare Mill. 150-250 weight portion, Root of Herba Cichorii 50-150 weight portion, Fructus Foeniculi 50-150 weight portion.
According to some currently preferred embodiments of the present invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 106 weight portion, seed of Herba Cichorii Intybi 212 weight portions, Semen Cuscutae 53 weight portion, root of Herba Apii graveolentis 212 weight portion, root bark of Foeniculum vulgare Mill. 212 weight portion, root of Herba Cichorii 106 weight Amount part, Fructus Foeniculi 106 weight portion.Thus, of a tightly knit structure, burden of liver is little, and toxic and side effects is little, to drug induccd hepatic injury Therapeutic effect is more preferably.The hepatic injury being prevented effectively from therapeutic process.
Term used herein " unit dose " refers to the drug dose of single administration, i.e. uses the hepatoprotective Bu Zure of a present invention During granule, the dosage of this hepatoprotective Bu Zure granule, corresponding unit dose can be determined according to the dosage form of hepatoprotective Bu Zure granule Organization.
According to some embodiments of the present invention, the dosage form of this hepatoprotective Bu Zure granule selected from mixture, injection, tablet, granule, One of syrup, capsule, oral liquid, aerosol and spray.
According to some embodiments of the present invention, this hepatoprotective Bu Zure granule provides with the form of hepatoprotective Bu Zure granule.Thus, Utilize existing commercially available dimension medicine hepatoprotective Bu Zure granule, drug induccd hepatic injury can be treated, control relative to more existing meanwhile Treating the medicine of drug induccd hepatic injury, this medicine reduces Serum ALT, and the advantage that AST mortality rate is low is especially pronounced, meanwhile, and should The composition letter of hepatoprotective Bu Zure granule is worked as, and burden of liver is little, and toxic and side effects is little, can be effectively prevented from over the course for the treatment of to liver Further damage.
According to another aspect of the invention, present invention also offers aforesaid hepatoprotective Bu Zure granule purposes in preparing medicine. According to embodiments of the invention, this medicine is used for treating drug induccd hepatic injury, and wherein, this hepatoprotective Bu Zure granule comprises: Herba Apii graveolentis Son, seed of Herba Cichorii Intybi, Semen Cuscutae, root of Herba Apii graveolentis, root bark of Foeniculum vulgare Mill., root of Herba Cichorii, Fructus Foeniculi.
Inventor has surprisingly found that, hepatoprotective Bu Zure granule can alleviate liver, the renomegaly that drug induccd hepatic injury causes effectively, Zoopery mortality rate is less, and safety is high, and significantly reduces Serum ALT, AST, recover hepatic tissue MDA, SOD, GSH-PX, significantly reduces the mortality rate of drug induccd hepatic injury, has good therapeutic effect to drug induccd hepatic injury, and, should Hepatoprotective Bu Zure particulate component letter is worked as, and burden of liver is little, and toxic and side effects is little, can be effectively prevented from over the course for the treatment of to liver Further damage.
According to a particular embodiment of the invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 50-150 weight portion, seed of Herba Cichorii Intybi 150-250 weight portion, Semen Cuscutae 20-100 weight portion, root of Herba Apii graveolentis 150-250 weight portion, root bark of Foeniculum vulgare Mill. 150-250 weight portion, Root of Herba Cichorii 50-150 weight portion, Fructus Foeniculi 50-150 weight portion.
According to some currently preferred embodiments of the present invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 106 weight portion, seed of Herba Cichorii Intybi 212 weight portions, Semen Cuscutae 53 weight portion, root of Herba Apii graveolentis 212 weight portion, root bark of Foeniculum vulgare Mill. 212 weight portion, root of Herba Cichorii 106 weight Amount part, Fructus Foeniculi 106 weight portion.Thus, of a tightly knit structure, burden of liver is little, and toxic and side effects is little, to drug induccd hepatic injury Therapeutic effect is more preferably.The hepatic injury being prevented effectively from therapeutic process.
According to some embodiments of the present invention, the medicine of the present invention can alleviate liver, the renal swelling that drug induccd hepatic injury causes effectively Greatly, zoopery mortality rate is less, and safety is high, and significantly reduces Serum ALT, AST, recovery hepatic tissue MDA, SOD, GSH-PX, significantly reduce the mortality rate of drug induccd hepatic injury, has good therapeutic effect to drug induccd hepatic injury, and And, the Bu Zure particulate component letter of this hepatoprotective is worked as, and burden of liver is little, and toxic and side effects is little, can be effectively prevented from over the course for the treatment of Further damage to liver.
According to a particular embodiment of the invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 50-150 weight portion, seed of Herba Cichorii Intybi 150-250 weight portion, Semen Cuscutae 20-100 weight portion, root of Herba Apii graveolentis 150-250 weight portion, root bark of Foeniculum vulgare Mill. 150-250 weight portion, Root of Herba Cichorii 50-150 weight portion, Fructus Foeniculi 50-150 weight portion.
According to some currently preferred embodiments of the present invention, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 106 weight portion, seed of Herba Cichorii Intybi 212 weight portions, Semen Cuscutae 53 weight portion, root of Herba Apii graveolentis 212 weight portion, root bark of Foeniculum vulgare Mill. 212 weight portion, root of Herba Cichorii 106 weight Amount part, Fructus Foeniculi 106 weight portion.Thus, of a tightly knit structure, burden of liver is little, and toxic and side effects is little, to drug induccd hepatic injury Therapeutic effect is more preferably.
According to some embodiments of the present invention, the dosage form of this medicine selected from mixture, injection, tablet, granule, syrup, One of capsule, oral liquid, aerosol and spray.Thus, it is simple to different according to being administered object, different dosage forms is used. Such as, for the ease of being administered, tablet, granule, syrup, capsule and oral liquid can be used, and it is possible to according to medicine The absorption site of thing and the release demand of medicine, be adjusted the dosage form of medicine, thus improve the bioavailability of medicine, prolong The release time of long medicine.For the person of being in a bad way, injection can be used, and then realize heavy dose of administration requirements, and, Avoid the gastrointestinal circulation impact on medicament effective component.
According to a particular embodiment of the invention, this medicine provides with the form of hepatoprotective Bu Zure granule.Thus, utilize existing Commercially available dimension medicine hepatoprotective Bu Zure granule, can treat drug induccd hepatic injury, meanwhile, relative to more existing treatment drug induccd livers The medicine of damage, this medicine reduces Serum ALT, and the effect that AST reduces mortality rate is especially pronounced, meanwhile, this medicines structure Letter is worked as, and burden of liver is little, and toxic and side effects is little, can be effectively prevented from the further damage over the course for the treatment of to liver.
Below with reference to specific embodiment, the present invention will be described, it should be noted that these embodiments are merely illustrative, And be not considered as limiting the invention.
Embodiment 1
Give test medicine by advance 1 week, then inject acetaminophen 400mg/kg by disposable celiac, cause KM Mice drug induccd liver injury model, after animal processes, observes mouse blood, liver tissue homogenate, internal organs, pathological section etc. and respectively refers to Mark, in similar drug, feature or odds ratio be relatively to the pharmacodynamic action of drug induccd hepatic injury and with it for evaluation test medicine.
1, experiment material
Animal: KM mice 70, SPF level, body weight 14~18g, male and female half and half, limited by Wuhan Biological Products Inst. Responsible company provides, animal credit number: SCXK (Hubei Province) 2012-0003.
Instrument: refiner, centrifuge, 96 orifice plates, 1.5ml Eppendorf manages, and 5ml Eppendorf manages, 10ml Eppendorf Pipe, weighs balance, operating theater instruments, microplate reader, light microscopic.
Reagent and medicine: formaldehyde, provided by Chemical Reagent Co., Ltd., Sinopharm Group;Compound liver-benepitino remedy, by China Resources Double-Crane Pharmaceutical Co., Ltd Limited company provides, lot number: 1405102;Liver is felt well granule, Baoding Tianhao Pharmaceutical Co., Ltd. provide, lot number: 140603; Acetaminophen, is provided by Aladdin, Lot#E1422053.
Test kit: ALT test kit, AST test kit, SOD test kit, MDA test kit, GSH-PX test kit, egg Bai Hanliang test kit, is provided by Wuhan Ke Rui Bioisystech Co., Ltd.
Method for preparation of drug:
Hepatoprotective Bu Zure granule:
320mg/ml (6.4g/kg): take 28.8g hepatoprotective Bu Zure granule, add 90ml distilled water, mixing, 4 DEG C of Refrigerator stores;
160mg/ml (3.2g/kg): take the hepatoprotective Bu Zure particle solution of 37.5ml 320mg/ml, add 37.5ml distilled water, mixed Even, 4 DEG C of Refrigerator stores;
80mg/ml (1.6g/kg): take the hepatoprotective Bu Zure particle solution of 25ml 160mg/ml, add 25ml distilled water, mixing, 4 DEG C of Refrigerator stores.
Comparison medicine compound liver-benepitino remedy:
Take 4.5 Fufang Yiganling tablets, grind into powder, add 42ml distilled water, mixing, 4 DEG C of Refrigerator stores.
Comparison medicine liver is felt well granule:
Take 3.36g liver to feel well granule, add 42ml distilled water, mixing, 4 DEG C of Refrigerator stores.
Acetaminophen:
20mg/ml (400mg/kg): take 0.84g acetaminophen, adds 42ml distilled water, mixing, 4 DEG C of Refrigerator stores.
2, experimental technique
Kunming mice 70 is only randomly divided into 7 groups.Normal group and model group equal-volume normal saline gavage, administration group is according to dosage Gavage, successive administration 7 days, after last is administered 1h, in addition to normal group, disposably give remaining and respectively organize lumbar injection to acetyl Amino phenols 400mg/kg, normal group lumbar injection 0.2ml/10g normal saline.24h after modeling, orbital venous plexus is taken a blood sample, and surveys Determine serum alt, AST content.Cervical dislocation put to death mice, weigh spleen, liver, kidney, thymic weight calculate dirty Device index.By spectrophotometry liver tissue homogenate MDA content, SOD activity, GSH-PX activity, at same position Cutting liver, 4% formaldehyde is fixed, and routine paraffin wax is cut into slices, and HE dyes, and makees pathological study under light microscopic.
3, statistics analytic method
Statistical procedures: all data all withRepresent, process with SPSS19.0 statistical software, many groups of measurement data Between compare employing variance analysis, between each group two-by-two compare employing T inspection.P < 0.05 is that difference is statistically significant.
4, experimental result
(1) commercially available compound liver-benepitino remedy granule, liver granule of feeling well is affected with by reagent hepatoprotective Bu Zure Granules on Mouse body weight
Result is visible, and normal group, model group gavage every day give normal saline, and the body weight of 7 days increases respectively 3.49g, 3.31g; 7 days weight gain value compared with normal groups of hepatoprotective Bu Zure granule and model group have increase trend, and hepatoprotective Bu Zure granule (1600mg/kg) there is significant difference, the results are shown in Table 1.
The impact (χ ± SD) of table 1. hepatoprotective Bu Zure Granules on Mouse body weight
Note: liver injury model Mus is that disposable ip gives acetaminophen 400mg/kg
#P < 0.05 compared with model group.
(2) hepatic injury is on Mouse Weight and the impact of mortality rate and the intervention effect of hepatoprotective Bu Zure granule
Result is visible, and compared with normal group weight gain value, model group Mouse Weight is remarkably decreased (P < 0.05);Compound recipe the liver benefiting Spirit group, liver granule group of feeling well can significantly reverse the weight loss caused by hepatic injury, and the hot granule of hepatoprotective cloth group (6400mg/kg) is to slow Solve weight loss and have certain trend;Liver injury model group mortality rate is 50%, the hot granule of hepatoprotective cloth group (6400mg/kg) Mortality rate is 20%, and less than other each group, the prompting hot granule of hepatoprotective cloth group (6400mg/kg) exists obvious anti-liver injury Effect, the results are shown in Table 2.(note: normal group weight loss is because processing caused by front fasting 12h).
Table 2
Note: liver injury model Mus is that disposable ip gives acetaminophen 400mg/kg
* P < 0.05 compared with normal group;#P < 0.05 compared with model group.
(3) drug induccd hepatic injury is on the impact of mice organs index and hepatoprotective Bu Zure granule intervention effect
After giving ip acetaminophen 400mg/kg 24h visible, liver, kiney edema, organ index significantly increases, and thymus is obvious Atrophy;Respectively by reagent group to liver, renal swelling is swollen all has some improvement, wherein hepatoprotective Bu Zure granule (6400mg/kg) Group, hepatoprotective Bu Zure granule (3200mg/kg) group can significantly reduce the liver organ index of poisoning by paracetamol Mus;Hepatoprotective Bu Zure granule (6400mg/kg) group can significantly reduce the kidney organ index of poisoning by paracetamol Mus, the results are shown in Table 3.
Table 3. drug induccd hepatic injury is on the impact of mice organs index and the intervention effect of hepatoprotective Bu Zure granule (χ±SD)
Note: liver injury model Mus is that disposable ip gives acetaminophen 400mg/kg
* P < 0.05, * * P < 0.01 compared with normal group;#P < 0.05, ##P < 0.01 compared with model group.
(4) the drug induccd hepatic injury intervention effect affecting hepatoprotective Bu Zure granule on mice serum ALT, AST activity
After giving ip acetaminophen 400mg/kg 24h visible, mice serum ALT, AST activity is notable to be raised, hepatoprotective cloth The hot granule of ancestral (1600mg/kg), hepatoprotective Bu Zure granule (3200mg/kg) can significantly reduce and be caused by drug induccd hepatic injury Serum ALT raises, hepatoprotective Bu Zure granule (6400mg/kg) group, hepatoprotective Bu Zure granule (3200mg/kg), hepatoprotective cloth Ancestral's hot granule (1600mg/kg) group can significantly reduce AST activity, liver function protecting in mice serum, the results are shown in Table 4..
Table 4. drug induccd hepatic injury on mice serum ALT, AST activity impact and the intervention effect (χ ± SD) of hepatoprotective Bu Zure granule
Note: liver injury model Mus is that disposable ip gives acetaminophen 400mg/kg
* * P < 0.01 compared with normal group;#P < 0.05 compared with model group;##P<0.01.
(5) drug induccd hepatic injury is on murine liver tissue MDA content, SOD activity and the impact of GSH-PX and hepatoprotective Bu Zure The intervention effect of granule
After giving ip acetaminophen 400mg/kg24h visible, SOD activity decrease in murine liver tissue, respectively by reagent pair SOD enzyme activity in damage hepatic tissue all has rising trend, but without significant difference;For GSH-PX vigor, each administration group Rising trend is all had compared with model group, but only compound liver-benepitino remedy granule (1600mg/kg), hepatoprotective Bu Zure granule (6400mg/kg), hepatoprotective Bu Zure granule (1600mg/kg) group has significant difference;Hepatoprotective Bu Zure granule (6400mg/kg), MDA in damage hepatic tissue is had by hepatoprotective Bu Zure granule (3200mg/kg), hepatoprotective Bu Zure granule (1600mg/kg) group Significance reduction effect, the results are shown in Table 5.
Table 5. drug induccd hepatic injury is on murine liver tissue MDA content, SOD activity and the impact of GSH-PX and hepatoprotective Bu Zure The intervention effect (χ ± SD) of granule
Note: liver injury model Mus is that disposable ip gives acetaminophen 400mg/kg
Compared with normal group*P<0.05;**P<0.01;Compared with model group#P<0.05;##P<0.01.
5, hepatic tissue section HE coloration result
From Fig. 1., after injection acetaminophen 24h, model group acetsminophen is obvious, and cell Cable Structure disappears, Cell sequence is disorderly, and hepatoprotective Bu Zure granule 6400mg/kg group mouse liver cell degeneration, degree of necrosis substantially alleviate, and pathological changes obtains To improve, and remaining group hepatic injury degree not be improved significantly.
6, conclusion
Weight loss that hepatoprotective Bu Zure granule causes for drug induccd hepatic injury, Liver and kidney enlargement, Serum ALT, AST raise, Hepatic tissue MDA activity reduces, and all shows certain mitigation, wherein, hepatoprotective cloth ancestral to hepatic tissue GSH-PX is abnormal The toxicity that hot granule (6400mg/kg) is organized is less, is better than positive control drug liver and feels well granule and compound liver-benepitino remedy granule, and hepatoprotective Bu Zure granule (3200mg/kg) has in the Liver and kidney enlargement caused by cushion and in terms of improving serum AST, ALT rising Preferably effect.Additionally, this pharmaceutical composition is of a tightly knit structure, burden of liver is little, and toxic and side effects is little, can be prevented effectively from treatment During further damage to liver.
In the description of this specification, reference term " embodiment ", " some embodiments ", " example ", " concrete example ", Or specific features, structure, material or the feature that the description of " some examples " etc. means to combine this embodiment or example describes comprises In at least one embodiment or example of the present invention.In this manual, the schematic representation to above-mentioned term not necessarily refers to It is identical embodiment or example.And, the specific features of description, structure, material or feature can at any one or Multiple embodiments or example combine in an appropriate manner.
Although an embodiment of the present invention has been shown and described, it will be understood by those skilled in the art that: without departing from this These embodiments can be carried out multiple change in the case of the principle of invention and objective, revise, replace and modification, the present invention's Scope is limited by claim and equivalent thereof.

Claims (4)

1. a hepatoprotective Bu Zure granule, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis, seed of Herba Cichorii Intybi, Semen Cuscutae, Herba Apii graveolentis Root, root bark of Foeniculum vulgare Mill., root of Herba Cichorii, Fructus Foeniculi, it is characterised in that described hepatoprotective Bu Zure granule is used for treating drug induccd hepatic injury.
Hepatoprotective Bu Zure granule the most according to claim 1, it is characterised in that described hepatoprotective Bu Zure granule comprises: Seed of Herba Apii graveolentis 50-150 weight portion, seed of Herba Cichorii Intybi 150-250 weight portion, Semen Cuscutae 20-100 weight portion, root of Herba Apii graveolentis 150-250 weight Amount part, root bark of Foeniculum vulgare Mill. 150-250 weight portion, root of Herba Cichorii 50-150 weight portion, Fructus Foeniculi 50-150 weight portion,
Preferably, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 106 weight portion, seed of Herba Cichorii Intybi 212 weight portion, Semen Cuscutae 53 weight portions, root of Herba Apii graveolentis 212 weight portion, root bark of Foeniculum vulgare Mill. 212 weight portion, root of Herba Cichorii 106 weight portion, Fructus Foeniculi 106 weight Amount part.
3. the purposes in preparing medicine of the hepatoprotective Bu Zure granule described in claim 1 or 2, described medicine is used for curative The hepatic injury of source property, wherein, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis, seed of Herba Cichorii Intybi, Semen Cuscutae, root of Herba Apii graveolentis, Radix Foeniculi Skin, root of Herba Cichorii, Fructus Foeniculi.
Purposes the most according to claim 3, it is characterised in that described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 50-150 Weight portion, seed of Herba Cichorii Intybi 150-250 weight portion, Semen Cuscutae 20-100 weight portion, root of Herba Apii graveolentis 150-250 weight portion, root bark of Foeniculum vulgare Mill. 150-250 weight portion, root of Herba Cichorii 50-150 weight portion, Fructus Foeniculi 50-150 weight portion,
Preferably, described hepatoprotective Bu Zure granule comprises: seed of Herba Apii graveolentis 106 weight portion, seed of Herba Cichorii Intybi 212 weight portion, Semen Cuscutae 53 weight portions, root of Herba Apii graveolentis 212 weight portion, root bark of Foeniculum vulgare Mill. 212 weight portion, root of Herba Cichorii 106 weight portion, Fructus Foeniculi 106 weight Amount part.
CN201610378270.5A 2016-05-31 2016-05-31 Application of Hugan Buzure particles in preparing medicine for treating drug induced liver injury Pending CN105998138A (en)

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CN112353764A (en) * 2020-06-15 2021-02-12 新疆维吾尔药业有限责任公司 Bozuri hot granules and extraction method and application thereof

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Application publication date: 20161012