CN102641469B - Medicinal composition for preventing or treating nonalcoholic steatohepatitis - Google Patents
Medicinal composition for preventing or treating nonalcoholic steatohepatitis Download PDFInfo
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Abstract
The invention discloses a medicinal composition for preventing or treating nonalcoholic steatohepatitis. The composition consists of gynostemma pentaphylla, radix curcumae, rhizoma atractylodis macrocephalae, silybum marianum, rhizoma alismatis, poria cocos, semen cassiae, salvia miltiorrhiza, seman sinapis albae and hawthorn. The medicinal composition disclosed by the invention has the functions of invigorating the spleen, soothing the liver, activating blood and eliminating turbid, and has an obvious effect on preventing or treating nonalcoholic steatohepatitis.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for the treatment of fat hepatitis, particularly relate to the pharmaceutical composition of a kind of prevention or treatment non-alcoholic stellato-hepatitis.
Background technology
Non-alcohol fatty liver (non-alcoholic fatty liver disease, NAFLD) has become one of clinical common hepatic disease, is the abnormal first cause of serum transaminase.Wherein non-alcoholic stellato-hepatitis (non-alcoholic steatohepatitis, NASH) be by non-alcoholic fatty liver disease (non-alcoholic fattyliver, NAFL) to a very important intermediate link in non-alcoholic fatty liver sclerosis (non-alcoholic cirrhosis) conversion process, be one of major reason of cryptogenic cirrhosis.Research shows, the prognosis of NASH is not good, and approximately 50% NASH can develop into hepatic fibrosis, and 15%～30% develops into liver cirrhosis, and 3% will develop into liver failure.Therefore, the control strategy of research NASH is one of study hotspot of at present domestic and international hepatopathy circle.
At present modern medicine there is no the specific medicament for the treatment of NAFLD, and mainly to dispel, the cause of disease and inducement, treatment are former sends out disease basic as main, to stop chronic hepatopathy development, control fat hepatitis; Latter stage at end, hepatopathy was with Liver Transplantation for Treatment.But the effect for the treatment of can not be satisfactory, especially NASH is with Hepatic enzyme change, hyperlipemia.And Chinese medicine has unique effect and advantage to the control of NASH, especially at the liver protecting and ALT lowering, improve liver function, regulate Liver Lipid Metabolism, reduce blood fat, improve on quality of life of patient and there is clear superiority.The point of theory that this research " is shown in the disease of liver, in the ban tonifying the spleen " from crucial pathogenesis " insufficiency of the spleen stagnation of liver-QI, phlegm-turbidity and blood stasis resistance " and the traditional medicine of NASH is set out, and control and found pharmaceutical composition of the present invention from liver spleen opinion, to reach invigorating the spleen and relieving depression of liver-QI, activating blood circulation to eliminate turbid, thus control NASH.
Summary of the invention
The object of the present invention is to provide the pharmaceutical composition of a kind of prevention or treatment non-alcoholic stellato-hepatitis.
Another object of the present invention is to provide the new purposes of a kind of prevention or treatment non-alcoholic stellato-hepatitis.
Pharmaceutical composition of the present invention is achieved by the following technical solution:
The crude drug of pharmaceutical composition of the present invention consists of:
Herb Gynostemmae Pentaphylli 7-23 weight portion Radix Curcumae 4-14 weight portion Rhizoma Atractylodis Macrocephalae 5-15 weight portion
Herba Silybi mariani 7-23 weight portion Rhizoma Alismatis 5-15 weight portion Poria 5-15 weight portion
Semen Cassiae 5-15 weight portion Radix Salviae Miltiorrhizae 7-23 weight portion Semen Sinapis Albae 3-9 weight portion
Fructus Crataegi 5-15 weight portion
The crude drug composition of pharmaceutical composition of the present invention is preferably:
The Herb Gynostemmae Pentaphylli 15 weight portion Radix Curcumae 9 weight portion Rhizoma Atractylodis Macrocephalae 10 weight portions
Herba Silybi mariani 15 weight portion Rhizoma Alismatis 10 weight portion Poria 10 weight portions
Semen Cassiae 10 weight portion Radix Salviae Miltiorrhizae 15 weight portion Semen Sinapis Albae 6 weight portions
Fructus Crataegi 10 weight portions
The crude drug of pharmaceutical composition of the present invention consists of:
The Herb Gynostemmae Pentaphylli 10 weight portion Radix Curcumae 11 weight portion Rhizoma Atractylodis Macrocephalae 7 weight portions
Herba Silybi mariani 20 weight portion Rhizoma Alismatis 7 weight portion Poria 12 weight portions
Semen Cassiae 7 weight portion Radix Salviae Miltiorrhizae 20 weight portion Semen Sinapis Albae 4 weight portions
Fructus Crataegi 12 weight portions
The crude drug of pharmaceutical composition of the present invention consists of:
The Herb Gynostemmae Pentaphylli 20 weight portion Radix Curcumae 7 weight portion Rhizoma Atractylodis Macrocephalae 12 weight portions
Herba Silybi mariani 10 weight portion Rhizoma Alismatis 12 weight portion Poria 7 weight portions
Semen Cassiae 12 weight portion Radix Salviae Miltiorrhizae 10 weight portion Semen Sinapis Albae 8 weight portions
Fructus Crataegi 7 weight portions
Pharmaceutical composition of the present invention adds conventional adjuvant to make the tablet of clinical acceptance, capsule, granule, pill, powder, oral liquid or injection according to common process.
Pharmaceutical composition of the present invention adds conventional adjuvant to make the slow releasing tablet of clinical acceptance, slow releasing capsule, sustained-release dropping pill or lyophilized injectable powder according to common process.
Pharmaceutical composition of the present invention has invigorating the spleen and relieving depression of liver-QI, effect of activating blood circulation to eliminate turbid.Remarkable to being used for the treatment of non-alcoholic stellato-hepatitis effect, have no side effect compared with Western medicine.
Experimental example is used for further illustrating the present invention below, but is not limited to the present invention.
The pharmacodynamic study test of experimental example pharmaceutical composition prevention of the present invention or treatment non-alcoholic stellato-hepatitis
1, medicine
(1), treatment group medicine (according to embodiment 1 method preparation)
Function cures mainly the present invention and has invigorating the spleen and relieving depression of liver-QI, effect of activating blood circulation to eliminate turbid.For preventing or treat the insufficiency of the spleen stagnation of liver-QI of non-alcoholic stellato-hepatitis, phlegm-turbidity and blood stasis resistance card.Disease is seen: fatigue and weakness, gastral cavity abdomen feeling of fullness, right flank distension or have mass in the abdomen, and doublely to see nauseating tending to vomit, obesity, uncomfortable in chestly do not relax, irritated irritability, the fat limit of light red tongue has indentation or dark tongue quality to have petechia, ecchymosis, and tongue is white greasy or yellow greasy, stringy and rolling pulse or thin and delicate.
Side's solution wherein Herb Gynostemmae Pentaphylli is sweet, bitter, cold, returns lung spleen kidney channel, invigorating the spleen and benefiting QI, blood activating and fat reducing, and Radix Curcumae is pungent, bitter, cold, returns liver cardiopulmonary warp, dispersing the stagnated live-QI to relieve the stagnation of QI, blood circulation promoting and blood stasis dispelling, the two plays invigorating the spleen and relieving depression of liver-QI altogether, therefore be monarch drug; The Rhizoma Atractylodis Macrocephalae is sweet, bitter, warm, returns taste warp, invigorating the spleen and benefiting QI, removing dampness the turbid descending, Herba Silybi mariani is cold in nature, bitter in the mouth, returns liver and gall warp, depressed liver-energy dispersing and function of gallbladder promoting, changes turbid blood fat reducing, Rhizoma Alismatis sweet light ooze let out, dampness removingization is turbid, three's principal drug assistance invigorating the spleen and relieving depression of liver-QI, and can dampness removingization turbid, is ministerial drug altogether; Poria is sweet, light, flat, GUIXIN spleen kidney channel, invigorating the spleen and benefiting QI, promoting diuresis with drugs of tasteless flavour, Semen Cassiae is sweet, bitter, salty, be slightly cold, and returns liver large intestine channel, and pancake liver-yang, relieving constipationization are turbid, Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling, clearing away heart-fire for tranquillization, Semen Sinapis Albae resolving phlegm lowering turbidity, resolving mass and removing the obstruction of the collateral, Fructus Crataegi invigorating the stomach and promoting digestion, blood stasis dispelling the turbid descending, be adjuvant altogether.Full side plays invigorating the spleen and relieving depression of liver-QI, activating blood circulation to eliminate turbid altogether.
(2), positive control drug high fat diet (HFD) rat model research positive control drug-polyene phosphatidylcholine (Essentiale N/Essentiale Forte N) capsule (specification: 228mg/ grain) of feeding, methionine-choline lacks diet (MCD) the mouse model research positive control drug-compound methionine choline sheet (DONGBAO GANTAI sheet) of feeding, Tonghua Dongbao Pharmaceutical Co., Ltd produces, product batch number: the accurate word H22024764 of traditional Chinese medicines.
2, pharmaceutical composition of the present invention prevention high fat diet (HFD) the NASH rat model research of feeding
(1), material
Feed formula and prepare high lipid food formula: 88% normal feedstuff+10% Adeps Sus domestica+2% cholesterol, by Beijing Australia of section feed corporation,Ltd's processing and fabricating of pulling together, is a clean level feedstuff, and room temperature is preserved.
Laboratory animal is selected SD male rat in 8～12 week age (body weight 120 ± 20g), is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..Laboratory animal routine is raised the clean level Animal House in Beijing University of Chinese Medicine, illumination in 12 hours and circulation at night, 22 ± 2 ℃ of temperature, humidity 50～60%.
(2), method
Animal grouping and dispose 40 rats and give normal diet adaptability and feed and be divided at random blank group, model group, prevention group of the present invention, Western medicine prevention after 1wk and organize 4 groups, every group 10, its empty group is given normal feedstuff+normal saline gavage, model group is given high lipid food+normal saline gavage, prevention group of the present invention is given high lipid food+medicine of the present invention (according to embodiment 1 method preparation) gavage, Western medicine prevention group is given high lipid food+Essentiale N/Essentiale Forte N suspension oral gavage, freely drink water, ingest, continuously 8wk.Rat is measured weekly body weight 2 times, observes animal feed, drinking-water, behavior, activity, the mental status, hair and two situation such as just every day; In prevention after finish the course for the treatment of, fasting/water 12h, weighs, anaesthetizes, gets blood, peels off the liver rear section liquid nitrogen cryopreservation of weighing, and part 4% paraformaldehyde is fixed for index and detects.
Serum liver function, blood fat and liver TG assay be large/and mice serum ALT, AST, CHO, TG, HDL, LDL adopt automatic clinical chemistry analyzer to measure; Liver TG measures: accurately take hepatic tissue 0.5g, adopt ultrasonic refiner to make homogenate (carrying out in frozen water), get 1% liver homogenate, get supernatant after centrifugal and measure liver TG content, test kit and instrument provide by Beijing Hua Ying test center.
Liver histopathology detects large/murine liver tissue frozen section, the conventional oil red O stain of row; Hepatic tissue paraffin section, row conventional H E dyeing.Under oil red O and HE section light microscopic, assess liver fat degeneration and course inflammatory activity situation.The NASH of NIH clinical research network pathology committee institute's definiteness south in 2005 that the pathological diagnosis standard of NASH adopts " Asian-Pacific area non-alcohol fatty liver Clinics and Practices common recognition " to recommend, assess according to the NAFLD mobility integration of its formulation (NAFLD Activity Score, NAS).NAS histological score system is to 14 pathological changes, 3 indexs have been carried out sxemiquantitative assessment score: hepatic steatosis is (by steatosis parenchyma/total cell number occurs, < 5%, 5%～33%, 33%～66%, > 66%, count respectively 0～3 point), inflammation in lobule (is pressed without focus, <2, 2～4, >4, count respectively 0～3 point), ballooning degeneration of liver cells is (by nothing, a small amount of balloon cells, more/significantly balloon sample becomes, count respectively 0～2 point), wherein NAS >=5 point person can be specified the diagnosis of NASH, 3 points of NAS < can get rid of NASH, person is NASH possibility between the two.Oil red O and HE section are used Olympus camera system to observe and take the photograph sheet.
Statistical procedures enumeration data represents with mean ± SD, adopts one factor analysis of variance to carry out statistical analysis, two-sided test P < 0.05 for significance,statistical, and statistical software adopts SPSS17.0.
(3), result
Serum liver function horizontal detection result compared with blank group, the Serum ALT of model group rat, AST all raise (P=0.005, P=0.017); Compared with model group, prevention group Serum ALT of the present invention, AST level obviously decline (P < 0.001, P=0.004), and Western medicine prevention group Serum ALT, AST also decline to some extent, but no difference of science of statistics (P=0.39, P=0.079); Compared with Western medicine prevention group, prevention group Serum ALT of the present invention, AST level decline by a big margin (P=0.003, P=0.178), especially aspect the improving of ALT level (in table 1, Fig. 1).
Table 1HFD rat liver function level (prevention)
Note: compared with blank group, ▲ P < 0.005, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 0.01.
Blood lipid level testing result is compared with blank group, and model group T-CHOL, triglyceride raise, and HDL, LDL decline, but equal no difference of science of statistics (P=0.097, P=0.091, P=0.212, P=0.894); Compared with model group, prevention group CHO of the present invention, TG, LDL all decline, HDL (the P=0.453 that raises, P=0.016, P=0.648, P=0.306), wherein only TG level has significant difference, Western medicine prevention is organized only serum TG and is declined to some extent, but no difference of science of statistics (P=0.276); Compared with Western medicine prevention group, prevention group change of serum C HO of the present invention, TG, LDL level all decline (P=0.059, P=0.15, P=0.137), but no difference of science of statistics (in table 2).
Table 2HFD Serum Lipids in Experimental HypercholesterolemicRats (prevention)
Note: compared with blank group, ▲ P < 0.05, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 0.01.
Hepatic tissue pathology testing result oil red O stain result shows: blank group liver tissues of rats has no red fat and drips; The visible a large amount of red fat of model group liver tissues of rats drips, and shows as fat and drips to fill the air and be impregnated in hepatocyte, merges in flakes, and fat drips cell number/total cell number and is about 54%.In prevention group of the present invention and Western medicine prevention group liver tissues of rats, also red color visible fat drips, but quantity is few compared with model group, and it is less to merge situation in blocks, and fat drips cell number proportion and is respectively 27%, 32%.
HE coloration result shows: blank group liver tissues of rats morphosis is all normal; Model group liver tissues of rats occurs that fat becomes, show as swelling of liver cell rounded, volume compared with normal obviously increases, in kytoplasm, visible significant quantities of fat cavity and balloon sample become, wherein visible inflammatory cell infiltration in portal area and lobule, be kitchen range shape and distribute, in lobules of liver, fat vacuole, ballooning degeneration of liver cells, inflammatory cell kitchen range infiltrate and deposit; Wherein hepatocellular damage mainly concentrates on middle acinus 3rd district, and inflammatory cell is take mononuclear cell, lymphocyte as main; Prevention group of the present invention and Western medicine prevention group liver tissues of rats fat become and alleviate compared with model group, and in lobules of liver, fat vacuole, the change of balloon sample and inflammatory infiltration all make moderate progress.(seeing Fig. 2)
Mark (in table 3) by NAS pathological score standard: compared with blank group, model group total score 6.33 ± 0.52 (P < 0.01), exceedes 5 points; Compared with model group, prevention group of the present invention and Western medicine prevention group total score obviously decline (P < 0.01), between 3～5 points; No difference of science of statistics between prevention group of the present invention and Western medicine prevention group.
The scoring of table 3HFD rat (prevention stage) pathological examination
Note: compared with blank group, ▲ P < 0.05, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 0.01.
3, pharmaceutical composition of the present invention is to high fat diet (HFD) the NASH rat effectiveness study of feeding
(1) material high lipid food formula and preparation, laboratory animal are with 2.
(2) method
Animal grouping and dispose 40 rats and give normal diet adaptability and feed and be divided at random 4 groups of blank groups, model group, of the present invention group, Western medicine group after 1wk, every group 10, its empty group is given normal feedstuff, and all the other each group is given high lipid food, freely drink water, ingest, continuously 8wk; After modeling finishes, blank group, model group are given normal saline gavage, of the present invention group is given medicine of the present invention (according to embodiment 1 method preparation) gavage, Western medicine group is given Essentiale N/Essentiale Forte N suspension oral gavage treatment (gavage dosage is by the ratiometric conversion of 1ml/100g rat dose,equivalent), cycle 4wk, once a day, during treatment, each group is all given normal feedstuff nursing, freely ingests, drinks water.Rat is measured weekly body weight 2 times, observes animal feed, drinking-water, behavior, activity, the mental status, hair and two situation such as just every day; In treatment after finish the course for the treatment of, fasting/water 12h, weighs, anaesthetizes, gets blood, peels off the liver rear section liquid nitrogen cryopreservation of weighing, and part 4% paraformaldehyde is fixed for index and detects.
Serum liver function, blood fat and liver TG assay wherein serum liver function, lipids detection method are the same; Liver TG assay: accurately take hepatic tissue 0.5g, adopt ultrasonic refiner to make homogenate (carrying out in frozen water), get 1% liver homogenate, get supernatant after centrifugal and measure liver TG content, test kit and instrument provide by Beijing Hua Ying test center.
Liver histopathology detects with 2.
Statistical procedures is with 2.
(3) result
Serum liver function horizontal detection result compared with blank group, Serum ALT, the AST of model group rat obviously raise (P < 0.001); Compared with model group, of the present invention group/Western medicine group Serum ALT, AST level be obviously decline (P < 0.001) all; Compared with Western medicine group, of the present invention group of Serum ALT levels declines (P=0.144) to some extent, but no difference of science of statistics, serum AST level no significant difference (in table 4, Fig. 3) between the two.
Table 4HFD rat liver function level (treatment)
Note: compared with blank group, ▲ P < 0.05, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 0.01.
Serum and liver TG content detection result are compared with blank group, and model group serum and liver TG content all raise (P=0.065, P < 0.001), especially liver TG content; Compared with model group, of the present invention group/Western medicine group liver TG content all significantly declines (P=0.011, P=0.048), and the horizontal no significant difference of serum TG; Serum and the equal no significant difference of liver TG content (in table 5, Fig. 4) between of the present invention group and Western medicine group.
Table 5HFD rat TG content (treatment)
Note: compared with blank group, ▲ P < 0.05, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 0.01.
Hepatic tissue pathology testing result oil red O stain result shows: blank group liver tissues of rats has no red fat and drips; The visible a large amount of red fat of model group liver tissues of rats drips, and shows as fat and drips to fill the air and be impregnated in hepatocyte, merges in flakes, and fat drips cell number/total cell number and is about 55%.In of the present invention group and Western medicine group liver tissues of rats, also red color visible fat drips, but quantity is few compared with model group, and it is less to merge situation in blocks, and fat drips cell number proportion and is respectively 25%, 35%.
HE coloration result shows: blank group liver tissues of rats morphosis is all normal; Model group liver tissues of rats occurs that fat becomes, show as swelling of liver cell rounded, volume compared with normal obviously increases, in kytoplasm, visible significant quantities of fat cavity and balloon sample become, wherein visible inflammatory cell infiltration in portal area and lobule, be kitchen range shape and distribute, in lobules of liver, fat vacuole, ballooning degeneration of liver cells, inflammatory cell kitchen range infiltrate and deposit; Wherein hepatocellular damage mainly concentrates on middle acinus 3rd district, and inflammatory cell is take mononuclear cell, lymphocyte as main; Of the present invention group and Western medicine group liver tissues of rats fat lesion alleviate compared with model group, fat vacuole, balloon sample just and inflammatory infiltration situation all make moderate progress.(seeing Fig. 5)
Mark (in table 6) by NAS pathological score standard: compared with blank group, model group total score 6.67 ± 0.52 (P < 0.01), exceedes 5 points; Compared with model group, of the present invention group and Western medicine group total score obviously decline (P < 0.01), between 3～5 points; No difference of science of statistics between of the present invention group and Western medicine group.
The scoring of table 6HFD rat (treatment stage) pathological examination
Note: compared with blank group, ▲ P < 0.05, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 0.01.
4, the pharmaceutical composition of the present invention prevention MCD NASH mouse model research of feeding
(1), material
Feed formula and prepare that methionine-choline lacks (MCD) feed formula (L-amino acids 175.7g/kg, Sucrose 441.9g/kg, Cornstarch 150.0g/kg, Dextromaltose 50.0g/kg, Cellulose30.0g/kg, Corn oi l 100.0g/kg, Sodium bicarbonate 7.4g/kg, Salt mix 35.0g/kg, Vitamin mix 10.0g/kg), MCD control diet MCS formula is on MCD feed formula basis, adds choline 2g/Kg, methionine 3g/Kg; MCD and MCS feedstuff, by Nantong Te Luofei feed corporation,Ltd processing and fabricating, are clean level feedstuff, 4 ℃ of cryopreservation.
Laboratory animal is selected the male ♂ mice of C57/BL6 in 8～12 week age (body weight 20 ± 2g), is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..Laboratory animal routine is raised the clean level Animal House in Beijing University of Chinese Medicine, illumination in 12 hours and circulation at night, 22 ± 2 ℃ of temperature, humidity 50～60%.
(2), method
Animal grouping and dispose 40 mices and give normal diet adaptability and feed and be divided at random blank group, model group, prevention group of the present invention, Western medicine prevention after 1wk and organize 4 groups, every group 10, its empty group MCS diet+normal saline gavage of feeding, model group MCD diet+normal saline gavage of feeding, prevention group of the present invention MCD diet+medicine of the present invention (according to embodiment 1 method preparation) gavage of feeding, Western medicine prevention group MCD diet+DONGBAO GANTAI sheet suspension oral gavage of feeding, freely ingest, drink water, continuously 2wk.Mice is measured weekly body weight 3 times, observes animal feed, drinking-water, behavior, activity, the mental status, hair and two situation such as just every day; In prevention after finish the course for the treatment of, fasting/water 12h, weighs, anaesthetizes, gets blood, peels off the liver rear section liquid nitrogen cryopreservation of weighing, and part 4% paraformaldehyde is fixed for index and detects.
Serum liver function, blood fat and liver TG assay are with 2.
Liver histopathology detects with 2.
Statistical procedures is with 2.
(3) result
Serum liver function horizontal detection result compared with blank group, Serum ALT, the AST of model group mice obviously raise (P < 0.001); Compared with model group, prevention group/Western medicine prevention group Serum ALT levels of the present invention all obviously decline (P=0.001, P < 0.001), though and serum AST level declines to some extent, no difference of science of statistics; Compared with Western medicine prevention group, prevention group of the present invention is slightly better than Western medicine prevention group (P=0.382) improving in serum AST level, but no difference of science of statistics, and Western medicine prevention group is better than Chinese herb on the prevention group (P=0.014) (in table 7, Fig. 6) improving in Serum ALT levels.
Table 7MCD mice liver function level
Note: compared with blank group, ▲ P < 0.05, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 0.01.
Serum and liver TG content detection result compared with blank group, model group serum TG low (P=0.12), and liver TG high (P=0.015); Compared with model group and Western medicine prevention group, prevention group liver TG content of the present invention obviously declines (P=0.005, P=0.023), and equal no significant difference (in table 8, Fig. 7) between serum TG level.
Table 8MCD mice TG content
Note: compared with blank group, ▲ P < 0.05, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 001.
Hepatic tissue pathology testing result oil red O stain result shows: blank group murine liver tissue has no red fat and drips; The visible a large amount of red fat of model group murine liver tissue drips, and shows as fat and drips to fill the air and be impregnated in hepatocyte, merges in flakes, and fat drips cell number/total cell number and is about 45～55%.In prevention group of the present invention and Western medicine prevention group murine liver tissue, also red color visible fat drips, but fat drips quantity compared with MCD group obviously less, and rare fat drips and merges in flakes, and fat drips cell number proportion and is respectively 25%, 20%.
HE coloration result shows: blank group murine liver tissue morphosis is all normal; Model group murine liver tissue occurs that fat becomes, structure disturbance, show as swelling of liver cell rounded, volume compared with normal obviously increases, visible fat vacuole in kytoplasm, wherein visible inflammatory cell infiltration in portal area and lobule, is kitchen range shape and distributes, and in lobules of liver, fat vacuole, ballooning degeneration of liver cells, inflammatory cell kitchen range infiltrate and deposit; Wherein hepatocellular damage mainly concentrates on middle acinus 1st district, and inflammatory cell is take mononuclear cell, lymphocyte as main; Prevention group of the present invention and Western medicine prevention group murine liver tissue fat lesion obviously alleviate compared with MCD group, and fat vacuole and inflammatory infiltration situation are all obviously improved, and balloon sample becomes basic and disappears.(seeing Fig. 8)
Mark (in table 9) by NAS pathological score standard: compared with blank group, model group total score 6.25 ± 0.50 (P < 0.01), exceedes 5 points; Compared with model group, prevention group of the present invention and Western medicine prevention group total score obviously decline (P < 0.01), especially Western medicine prevention group; No difference of science of statistics between prevention group of the present invention and Western medicine prevention group.
The scoring of table 9MCD mice (prevention stage) pathological examination
Note: compared with blank group, ▲ P < 0.05, ▲ ▲ P < 0.01; Compared with model group, * P < 0.05, * * P < 0.01.
5, conclusion
Above three pharmacodynamic studies show: the present invention can effectively prevent and treat the HFD NASH rat of feeding, and it all has obvious curative effects improving aspect rat blood serum ALT, AST, serum and liver TG content and hepatic pathology, has some superiority compared with Western medicine Essentiale N/Essentiale Forte N; The present invention feeds aspect NASH mice and has equally obvious curative effects at prevention MCD diet, it can obviously reduce mice serum ALT level, liver TG content, improve liver fat lesion degree, and no significant difference between compound methionine choline sheet (DONGBAO GANTAI PIAN).The present invention is that prevention or treatment all have remarkable result for NASH nutrition induced animal model (HFD rat model and MCD mouse model).
Accompanying drawing explanation
Fig. 1 HFD rat liver function level (prevention)
Fig. 2 HFD liver tissues of rats pathological examination (prevention)
Fig. 3 HFD rat liver function level (treatment)
Fig. 4 HFD rat TG content (treatment)
Fig. 5 HFD liver tissues of rats pathological examination (treatment)
Fig. 6 MCD mice liver function level
Fig. 7 MCD mice TG content
Fig. 8 MCD murine liver tissue pathological examination (prevention)
Following embodiment is used for further illustrating the present invention, but is not limited to the present invention.
The specific embodiment
Embodiment 1: granule
Herb Gynostemmae Pentaphylli 15kg Radix Curcumae 9kg Rhizoma Atractylodis Macrocephalae 10kg
Herba Silybi mariani 15kg Rhizoma Alismatis 10kg Poria 10kg
Semen Cassiae 10kg Radix Salviae Miltiorrhizae 15kg Semen Sinapis Albae 6kg
Fructus Crataegi 10kg
Above-mentioned raw materials medicine is added to the agent of conventional adjuvant granulation according to common process.10 grams every bag, every day 2 times, each 1 bag.
Embodiment 2: tablet
Herb Gynostemmae Pentaphylli 10kg Radix Curcumae 11kg Rhizoma Atractylodis Macrocephalae 7kg
Herba Silybi mariani 20kg Rhizoma Alismatis 7kg Poria 12kg
Semen Cassiae 7kg Radix Salviae Miltiorrhizae 20kg Semen Sinapis Albae 4kg
Fructus Crataegi 12kg
Add conventional adjuvant to make tablet according to common process above-mentioned raw materials medicine.
Embodiment 3: capsule
Herb Gynostemmae Pentaphylli 20kg Radix Curcumae 7kg Rhizoma Atractylodis Macrocephalae 12kg
Herba Silybi mariani 10kg Rhizoma Alismatis 12kg Poria 7kg
Semen Cassiae 12kg Radix Salviae Miltiorrhizae 10kg Semen Sinapis Albae 8kg
Fructus Crataegi 7kg
Add conventional adjuvant to make capsule according to common process above-mentioned raw materials medicine.
Embodiment 4: oral liquid
Herb Gynostemmae Pentaphylli 15kg Radix Curcumae 9kg Rhizoma Atractylodis Macrocephalae 10kg
Herba Silybi mariani 15kg Rhizoma Alismatis 10kg Poria 10kg
Semen Cassiae 10kg Radix Salviae Miltiorrhizae 15kg Semen Sinapis Albae 6kg
Fructus Crataegi 10kg
Add conventional adjuvant to make oral liquid according to common process above-mentioned raw materials medicine.
Embodiment 5: sustained-release dropping pill
Herb Gynostemmae Pentaphylli 10kg Radix Curcumae 11kg Rhizoma Atractylodis Macrocephalae 7kg
Herba Silybi mariani 20kg Rhizoma Alismatis 7kg Poria 12kg
Semen Cassiae 7kg Radix Salviae Miltiorrhizae 20kg Semen Sinapis Albae 4kg
Fructus Crataegi 12kg
Add conventional adjuvant to make sustained-release dropping pill according to common process above-mentioned raw materials medicine.
Embodiment 6: injection
Herb Gynostemmae Pentaphylli 20kg Radix Curcumae 7kg Rhizoma Atractylodis Macrocephalae 12kg
Herba Silybi mariani 10kg Rhizoma Alismatis 12kg Poria 7kg
Semen Cassiae 12kg Radix Salviae Miltiorrhizae 10kg Semen Sinapis Albae 8kg
Fructus Crataegi 7kg
Add conventional adjuvant to make injection according to common process above-mentioned raw materials medicine.
Embodiment 7: lyophilized injectable powder
Herb Gynostemmae Pentaphylli 15kg Radix Curcumae 9kg Rhizoma Atractylodis Macrocephalae 10kg
Herba Silybi mariani 15kg Rhizoma Alismatis 10kg Poria 10kg
Semen Cassiae 10kg Radix Salviae Miltiorrhizae 15kg Semen Sinapis Albae 6kg
Fructus Crataegi 10kg
Add conventional adjuvant to make lyophilized injectable powder according to common process above-mentioned raw materials medicine.
Claims (6)
1. a pharmaceutical composition for prevention or treatment non-alcoholic stellato-hepatitis, is characterized in that this
Compositions is made up of following crude drug:
Herb Gynostemmae Pentaphylli 15kg Radix Curcumae 9kg Rhizoma Atractylodis Macrocephalae 10kg
Herba Silybi mariani 15kg Rhizoma Alismatis 10kg Poria 10kg
Semen Cassiae 10kg Radix Salviae Miltiorrhizae 15kg Semen Sinapis Albae 6kg
Fructus Crataegi 10kg.
2. pharmaceutical composition as claimed in claim 1, is characterized in that said composition adds conventional adjuvant to make the tablet of clinical acceptance, capsule, granule, pill, powder, oral liquid or injection according to common process.
3. pharmaceutical composition as claimed in claim 1, is characterized in that said composition adds conventional adjuvant to make the slow releasing tablet of clinical acceptance, slow releasing capsule, sustained-release dropping pill or lyophilized injectable powder according to common process.
4. the application of pharmaceutical composition as claimed in claim 1 in the medicine of preparation prevention or treatment non-alcoholic stellato-hepatitis.
5. application as claimed in claim 4, is characterized in that described prevention or treatment non-alcoholic stellato-hepatitis refer to reduction Serum ALT, AST or TG level.
6. application as claimed in claim 4, is characterized in that described prevention or treatment non-alcoholic stellato-hepatitis refer to reduction liver TG content.
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| CN201110042447.1A CN102641469B (en) | 2011-02-22 | 2011-02-22 | Medicinal composition for preventing or treating nonalcoholic steatohepatitis |
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| CN201110042447.1A CN102641469B (en) | 2011-02-22 | 2011-02-22 | Medicinal composition for preventing or treating nonalcoholic steatohepatitis |
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| CN105560779B (en) * | 2014-10-15 | 2019-11-12 | 上海中医药大学附属龙华医院 | The compound preparation and application thereof for preventing and treating non-alcohol fatty liver |
| CN105535846B (en) * | 2016-01-19 | 2019-07-12 | 北京中医药大学东方医院 | A kind of preparation method of invigorating spleen and soothing liver Chinese medicine composition |
| CN114558099A (en) * | 2022-03-29 | 2022-05-31 | 沈阳市第六人民医院 | Traditional Chinese medicine composition and preparation method and application thereof |
| CN116115724B (en) * | 2023-03-30 | 2023-12-12 | 北京中医药大学 | Traditional Chinese medicine composition, pharmaceutical preparation, preparation method and application thereof |
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| CN101181368A (en) * | 2007-11-21 | 2008-05-21 | 北京中科雍和医药技术有限公司 | Compound prescription for defending and protecting hepar as well as preparation technique thereof |
| CN101272799A (en) * | 2005-08-12 | 2008-09-24 | 凡诺华（英国）有限公司 | Plant-based medicament for the treatment of liver disease |
| CN101274044A (en) * | 2008-05-15 | 2008-10-01 | 天科仁祥技术（北京）有限责任公司 | Medicament for preventing and treating fatty liver and method of preparing the same |
| CN101829225A (en) * | 2010-04-01 | 2010-09-15 | 刘元杰 | Micro circulation smoothing health-care product and preparation method thereof |
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| CN1435249A (en) * | 2003-03-14 | 2003-08-13 | 蒋盘宏 | Chinese patent medicine for treating hyperlipidemia and fatty liver and preparing process thereof |
| CN101401920B (en) * | 2008-11-06 | 2011-01-19 | 刘秋兰 | Traditional Chinese medicine preparation for treating fatty liver |
| CN101496894B (en) * | 2009-03-19 | 2012-05-02 | 天津市传染病医院 | Medicament for treating fatty liver and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101272799A (en) * | 2005-08-12 | 2008-09-24 | 凡诺华（英国）有限公司 | Plant-based medicament for the treatment of liver disease |
| CN101181368A (en) * | 2007-11-21 | 2008-05-21 | 北京中科雍和医药技术有限公司 | Compound prescription for defending and protecting hepar as well as preparation technique thereof |
| CN101274044A (en) * | 2008-05-15 | 2008-10-01 | 天科仁祥技术（北京）有限责任公司 | Medicament for preventing and treating fatty liver and method of preparing the same |
| CN101829225A (en) * | 2010-04-01 | 2010-09-15 | 刘元杰 | Micro circulation smoothing health-care product and preparation method thereof |
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