CN102641469A - 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 of treating fat hepatitis, particularly relate to the pharmaceutical composition of a kind of prevention or treatment non-alcoholic stellato-hepatitis.
Background technology
(non-alcoholic fatty liver disease NAFLD) has become one of clinical common hepatic disease to non-alcohol fatty liver, is the unusual first cause of serum transaminase.Non-alcoholic stellato-hepatitis (non-alcoholic steatohepatitis wherein; NASH) be by non-alcoholic fatty liver disease (non-alcoholic fattyliver; NAFL) very important intermediate link in non-alcoholic fatty liver sclerosis (non-alcoholic cirrhosis) conversion process is one of major reason of cryptogenic cirrhosis.Research shows that the prognosis of NASH is not good, and about 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 research focus of at present domestic and international hepatopathy circle.
At present modern medicine does not still have the specific medicament of treatment NAFLD, and mainly former to send out disease basic be main to dispel the cause of disease and inducement, treatment, to stop the chronic hepatopathy development, the control fat hepatitis; Latter stage at end, hepatopathy was then with Liver Transplantation for Treatment.But the effect of treatment can not be satisfactory, and especially NASH is with the change of liver zymetology, hyperlipemia.And Chinese medicine has unique effect and advantage to the control of NASH, especially at the liver protecting and ALT lowering, improves liver function, regulates the liver lipid metabolism, and blood fat reducing improves on quality of life of patient and has clear superiority.The theory point of view that this research " is seen the disease of liver, in the ban tonifying the spleen " from the crucial pathogenesis of NASH " insufficiency of the spleen stagnation of liver-QI, phlegm-turbidity and blood stasis resistance " and traditional medicine is controlled from liver spleen opinion and to be founded pharmaceutical composition of the present invention, reaching 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 realized through following technical scheme:
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 Curcumaes 9 weight portion Rhizoma Atractylodis Macrocephalaes 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 Miltiorrhizaes 15 weight portion Semen Sinapis Albaes 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 Curcumaes 11 weight portion Rhizoma Atractylodis Macrocephalaes 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 Miltiorrhizaes 20 weight portion Semen Sinapis Albaes 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 Curcumaes 7 weight portion Rhizoma Atractylodis Macrocephalaes 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 Miltiorrhizaes 10 weight portion Semen Sinapis Albaes 8 weight portions
Fructus Crataegi 7 weight portions
Pharmaceutical composition of the present invention adds conventional adjuvant according to common process and processes the tablet of clinical acceptance, capsule, granule, pill, powder, oral liquid or injection.
Pharmaceutical composition of the present invention adds conventional adjuvant according to common process and processes the slow releasing tablet of clinical acceptance, slow releasing capsule, sustained-release dropping pill or lyophilized injectable powder.
Pharmaceutical composition of the present invention has invigorating the spleen and relieving depression of liver-QI, the effect of activating blood circulation to eliminate turbid.Remarkable to being used to treat the non-alcoholic stellato-hepatitis effect, compare with Western medicine and to have no side effect.
Following experimental example is used to further specify the present invention, 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 the preparation of embodiment 1 method)
Function cures mainly the present invention and has invigorating the spleen and relieving depression of liver-QI, the effect of activating blood circulation to eliminate turbid.Be used for prevention or the insufficiency of the spleen stagnation of liver-QI of treatment non-alcoholic stellato-hepatitis, phlegm-turbidity and blood stasis resistance card.Disease is seen: fatigue and weakness, gastral cavity abdomen feeling of fullness, right side of body distension or mass in the abdomen is arranged, doublely see nauseating tending to vomit, obesity, uncomfortable in chestly do not relax, irritated irritability that the fat limit of light red tongue has indentation or dark tongue quality that petechia, ecchymosis are arranged, and tongue is greasy in vain or yellow greasy, stringy and rolling pulse or thin and delicate.
It is sweet, bitter, cold that the side separates wherein Herb Gynostemmae Pentaphylli, returns lung spleen kidney channel, invigorating the spleen and benefiting QI, blood activating and fat reducing, and Radix Curcumae is hot, bitter, tremble with fear, and 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, so be monarch drug; The Rhizoma Atractylodis Macrocephalae is sweet, bitter, warm, returns the taste warp, invigorating the spleen and benefiting QI, removing dampness the turbid descending, cold in nature, the bitter in the mouth of Herba Silybi mariani is returned the 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, but and dampness removingization turbid, be 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 the 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 are 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: the 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 preparation high lipid food prescription: 88% normal feedstuff+10% Adeps Sus domestica+2% cholesterol by Beijing section Australia feed corporation,Ltd's processing and fabricating of pulling together, is a cleaning level feedstuff, and room temperature is preserved.
Laboratory animal select for use 8～12 the week age SD male rat (body weight 120 ± 20g) is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..The laboratory animal routine is raised the cleaning 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 divides into groups and disposes 40 rats and give the normal diet adaptability and feed and be divided into blank control group, model group, prevention group of the present invention, Western medicine prevention behind the 1wk at random and organize 4 groups; Every group 10, wherein blank control group is given normal feedstuff+normal saline and is irritated stomach, and model group is given high lipid food+normal saline and irritated stomach; Prevention group of the present invention is given high lipid food+medicine of the present invention (according to the preparation of embodiment 1 method) and is irritated stomach; Western medicine prevention group is given high lipid food+Essentiale N/Essentiale Forte N suspension oral gavage, freely drinks water, ingests, continuously 8wk.Rat is measured body weight weekly 2 times, observes animal feed, drinking-water, behavior, activity, the mental status, hair and two every day and just waits situation; After prevention finished the course of treatment, fasting/water 12h was weighed, anaesthetizes, is got 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 big/and mice serum ALT, AST, CHO, TG, HDL, LDL adopt automatic clinical chemistry analyzer to measure; Liver TG measures: accurately take by weighing hepatic tissue 0.5g, adopt ultrasonic refiner to process homogenate (carrying out in the frozen water), get 1% LH, get supernatant after centrifugal to measure liver TG content, test kit and instrument provide by Beijing Hua Ying test center.
Liver histopathology detects big/murine liver tissue frozen section, the conventional oil red O stain of row; The hepatic tissue paraffin section, row conventional H E dyeing.Oil red O and HE section light microscopic be assessment liver fat degeneration and inflammation active situation down.Institute in 2005 of the NASH of the NIH clinical research network pathology committee definiteness south that the pathological diagnosis standard of NASH adopts " Asian-Pacific area non-alcohol fatty liver Clinics and Practices common recognition " to recommend; (NAFLD Activity Score NAS) assesses according to the NAFLD mobility integration of its formulation.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 takes place;＜5%, 5%～33%, 33%～66%,＞66%, counted respectively 0～3 fen), inflammation (, counting respectively 0～3 fen) in the lobule, ballooning degeneration of liver cells by no focus,<2,2～4,>4 (by do not have, a small amount of balloon cells, more/significantly balloon appearance change; Counted respectively 0～2 fen); The diagnosis that wherein NAS>=5 minute person can clear and definite NASH, NAS＜3 minute then can be got rid of NASH, and the person is that NASH maybe between the two.Oil red O and HE section use the Olympus camera system to observe and take the photograph sheet.
The statistical procedures enumeration data is represented with mean ± SD, adopts one factor analysis of variance to carry out statistical analysis, and significance,statistical is with two-sided test P＜0.05, and statistical software adopts SPSS17.0.
(3), result
Serum liver function horizontal detection is the result compare with blank control group, Serum ALT, the AST of model group rat all raise (P=0.005, P=0.017); Compare with model group, prevention group Serum ALT of the present invention, AST level obviously descend (P＜0.001, P=0.004), Western medicine prevention group Serum ALT, AST also descend to some extent, but no difference of science of statistics (P=0.39, P=0.079); Compare 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 (seeing table 1, Fig. 1).
Table 1HFD rat liver function level (prevention)
Annotate: compare with blank control group, ▲ P＜0.005, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜0.01 with model group.
The blood lipid level testing result is compared with blank control group, and model group T-CHOL, triglyceride raise, and HDL, LDL descend, but equal no difference of science of statistics (P=0.097, P=0.091, P=0.212, P=0.894); Compare with model group, prevention group CHO of the present invention, TG, LDL all descend, the HDL (P=0.453 that raises; P=0.016, P=0.648, P=0.306); Wherein only the TG level has significant difference, and the Western medicine prevention only organizes that serum TG descends to some extent, but no difference of science of statistics (P=0.276); Compare with Western medicine prevention group, prevention group change of serum C HO of the present invention, TG, LDL level all descend (P=0.059, P=0.15, P=0.137), but no difference of science of statistics (seeing table 2).
Table 2HFD rat fat level (prevention)
Annotate: compare with blank control group, ▲ P＜0.05, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜0.01 with model group.
Hepatic tissue pathology testing result oil red O stain result shows: blank control group liver tissues of rats not show color fat is dripped; The visible a large amount of red fat of model group liver tissues of rats drip, and show as fat and drip to fill the air and be impregnated in the hepatocyte, merge in flakes, and fat drips cell number/total cell number and is about 54%.In prevention group of the present invention and the Western medicine prevention group liver tissues of rats also red color visible fat drip, but quantity is few than model group, and it is less to merge situation in blocks, fat drips the cell number proportion and is respectively 27%, 32%.
The HE coloration result shows: blank control group liver tissues of rats morphosis is all normal; The model group liver tissues of rats fat occurs and becomes; It is rounded to show as swelling of liver cell; Volume is normal obviously to be increased, and visible significant quantities of fat cavity and balloon appearance become in the kytoplasm, wherein visible inflammatory cell infiltration in portal area and the lobule; Be the kitchen range shape and distribute, lobules of liver interior fat vacuole, ballooning degeneration of liver cells, the property infiltration of inflammatory cell kitchen range are also deposited; Acinus 3 districts during wherein hepatocellular damage mainly concentrates on, inflammatory cell is main with mononuclear cell, lymphocyte; Prevention group of the present invention and Western medicine prevention group liver tissues of rats fat become and alleviate than model group, and fat vacuole, the change of balloon appearance and inflammatory infiltration all make moderate progress in the lobules of liver.(see figure 2)
Mark (seeing table 3) by NAS pathological score standard: compare with blank control group, model group total points 6.33 ± 0.52 (P＜0.01) was above 5 minutes; Compare with model group, prevention group of the present invention and Western medicine prevention group total points obviously descend (P＜0.01), between 3～5 minutes; No difference of science of statistics between prevention group of the present invention and the Western medicine prevention group.
The scoring of table 3HFD rat (prevention stage) pathological examination
Annotate: compare with blank control group, ▲ P＜0.05, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜0.01 with model group.
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 prescription and preparation, laboratory animal are with 2.
(2) method
Animal divides into groups and disposes 40 rats and give the normal diet adaptability and feed and be divided into 4 groups of blank control group, model group, of the present invention group, Western medicine group behind the 1wk at random; Every group 10, wherein blank control group is given normal feedstuff, and all the other each groups are given high lipid food; Freely drink water, ingest, continuously 8wk; After modeling finishes; Blank control group, model group are given normal saline and are irritated stomach, and of the present invention group is given medicine of the present invention (according to the preparation of embodiment 1 method) filling stomach, and Western medicine group is given Essentiale N/Essentiale Forte N suspension oral gavage treatment (irritate stomach dosage and press the ratiometric conversion of 1ml/100g rat dose,equivalent); Cycle 4wk; Once a day, each group is all given the normal feedstuff nursing during the treatment, freely ingests, drinks water.Rat is measured body weight weekly 2 times, observes animal feed, drinking-water, behavior, activity, the mental status, hair and two every day and just waits situation; After treatment finished the course of treatment, fasting/water 12h was weighed, anaesthetizes, is got 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 by weighing hepatic tissue 0.5g, adopt ultrasonic refiner to process homogenate (carrying out in the frozen water), get 1% LH, 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 is the result compare with blank control group, Serum ALT, the AST of model group rat obviously raise (P＜0.001); Compare with model group, of the present invention group/Western medicine group Serum ALT, AST level be obviously decline (P＜0.001) all; Compare with Western medicine group, of the present invention group of Serum ALT levels descends (P=0.144) to some extent, but no difference of science of statistics, serum AST level no significant difference (seeing table 4, Fig. 3) between the two.
Table 4HFD rat liver function level (treatment)
Annotate: compare with blank control group, ▲ P＜0.05, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜0.01 with model group.
Serum and liver TG content detection result compare with blank control group, model group serum and liver TG content all raise (P=0.065, P＜0.001), especially liver TG content; Compare with model group, all significantly decline of of the present invention group/Western medicine group liver TG content (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 (seeing table 5, Fig. 4) between of the present invention group and the Western medicine group.
Table 5HFD rat TG content (treatment)
Annotate: compare with blank control group, ▲ P＜0.05, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜0.01 with model group.
Hepatic tissue pathology testing result oil red O stain result shows: blank control group liver tissues of rats not show color fat is dripped; The visible a large amount of red fat of model group liver tissues of rats drip, and show as fat and drip to fill the air and be impregnated in the hepatocyte, merge in flakes, and fat drips cell number/total cell number and is about 55%.In of the present invention group and the Western medicine group liver tissues of rats also red color visible fat drip, but quantity is few than model group, and it is less to merge situation in blocks, fat drips the cell number proportion and is respectively 25%, 35%.
The HE coloration result shows: blank control group liver tissues of rats morphosis is all normal; The model group liver tissues of rats fat occurs and becomes; It is rounded to show as swelling of liver cell; Volume is normal obviously to be increased, and visible significant quantities of fat cavity and balloon appearance become in the kytoplasm, wherein visible inflammatory cell infiltration in portal area and the lobule; Be the kitchen range shape and distribute, lobules of liver interior fat vacuole, ballooning degeneration of liver cells, the property infiltration of inflammatory cell kitchen range are also deposited; Acinus 3 districts during wherein hepatocellular damage mainly concentrates on, inflammatory cell is main with mononuclear cell, lymphocyte; Of the present invention group and Western medicine group liver tissues of rats fat lesion alleviate than model group, fat vacuole, balloon appearance just and the inflammatory infiltration situation all make moderate progress.(see figure 5)
Mark (seeing table 6) by NAS pathological score standard: compare with blank control group, model group total points 6.67 ± 0.52 (P＜0.01) was above 5 minutes; Compare with model group, of the present invention group and Western medicine group total points obviously descend (P＜0.01), between 3～5 minutes; No difference of science of statistics between of the present invention group and the Western medicine group.
The scoring of table 6HFD rat (treatment stage) pathological examination
Annotate: compare with blank control group, ▲ P＜0.05, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜0.01 with model group.
4, the pharmaceutical composition of the present invention prevention MCD NASH mouse model research of feeding
(1), material
Feed formula and preparation methionine-choline lack (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 prescription is on MCD feed formula basis, add choline 2g/Kg, methionine 3g/Kg; MCD and MCS feedstuff are cleaning level feedstuff, 4 ℃ of cryopreservation by Nantong Te Luofei feed corporation,Ltd processing and fabricating.
Laboratory animal is selected the male ♂ mice of 8～12 week C57/BL6 in age for use, and (body weight 20 ± 2g) is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..The laboratory animal routine is raised the cleaning 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 divides into groups and disposes 40 mices and give the normal diet adaptability and feed and be divided into blank control group, model group, prevention group of the present invention, Western medicine prevention behind the 1wk at random and organize 4 groups; Every group 10; Wherein feed MCS diet+normal saline of blank control group is irritated stomach; Feed MCD diet+normal saline of model group is irritated stomach, and the prevention group of the present invention MCD diet+medicine of the present invention (according to the preparation of embodiment 1 method) of feeding is irritated stomach, the Western medicine prevention group MCD diet+DONGBAO GANTAI sheet suspension oral gavage of feeding; Freely ingest, drink water, continuously 2wk.Mice is measured body weight weekly 3 times, observes animal feed, drinking-water, behavior, activity, the mental status, hair and two every day and just waits situation; After prevention finished the course of treatment, fasting/water 12h was weighed, anaesthetizes, is got 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 is the result compare with blank control group, Serum ALT, the AST of model group mice obviously raise (P＜0.001); Compare with model group, prevention group of the present invention/Western medicine prevention group Serum ALT levels all obviously descends (P=0.001, P＜0.001), though and serum AST level descends to some extent, no difference of science of statistics; Compare with Western medicine prevention group, prevention group of the present invention slightly is superior to Western medicine prevention group (P=0.382) improving on the serum AST level, but no difference of science of statistics, and Western medicine prevention group is superior to Chinese herb on the prevention group (P=0.014) (seeing table 7, Fig. 6) improving on the Serum ALT levels.
Table 7MCD mice liver function level
Annotate: compare with blank control group, ▲ P＜0.05, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜0.01 with model group.
Serum and liver TG content detection result compare with blank control group, model group serum TG low (P=0.12), and liver TG high (P=0.015); Compare with model group and Western medicine prevention group, prevention group liver TG content of the present invention obviously descend (P=0.005, P=0.023), and equal no significant difference (seeing table 8, Fig. 7) between the serum TG level.
Table 8MCD mice TG content
Annotate: compare with blank control group, ▲ P＜0.05, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜001 with model group.
Hepatic tissue pathology testing result oil red O stain result shows: blank control group murine liver tissue not show color fat is dripped; The visible a large amount of red fat of model group murine liver tissue drip, and show as fat and drip to fill the air and be impregnated in the hepatocyte, merge in flakes, and fat drips cell number/total cell number and is about 45～55%.In prevention group of the present invention and the Western medicine prevention group murine liver tissue also red color visible fat drip, but that fat drips quantity is obviously few than MCD group, rare fat drips and merges in flakes, fat drips the cell number proportion and is respectively 25%, 20%.
The HE coloration result shows: blank control group murine liver tissue morphosis is all normal; The model group murine liver tissue fat occurs and becomes; Structure disturbance, it is rounded to show as swelling of liver cell, and volume is normal obviously to be increased; Visible fat vacuole in the kytoplasm; Wherein visible inflammatory cell infiltration in portal area and the lobule is the kitchen range shape and distributes, and lobules of liver interior fat vacuole, ballooning degeneration of liver cells, the property infiltration of inflammatory cell kitchen range are also deposited; Acinus 1 district during wherein hepatocellular damage mainly concentrates on, inflammatory cell is main with mononuclear cell, lymphocyte; Prevention group of the present invention and Western medicine prevention group murine liver tissue fat lesion obviously alleviate than the MCD group, and fat vacuole and inflammatory infiltration situation are all obviously improved, and balloon appearance becomes basic and disappears.(see figure 8)
Mark (seeing table 9) by NAS pathological score standard: compare with blank control group, model group total points 6.25 ± 0.50 (P＜0.01) was above 5 minutes; Compare prevention group of the present invention and Western medicine prevention group total points obviously descend (P＜0.01), especially Western medicine prevention group with model group; No difference of science of statistics between prevention group of the present invention and the Western medicine prevention group.
The scoring of table 9MCD mice (prevention stage) pathological examination
Annotate: compare with blank control group, ▲ P＜0.05, ▲ ▲ P＜0.01; Compare * P＜0.05, * * P＜0.01 with model group.
5, conclusion
More than 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 aspect rat blood serum ALT, AST, serum and liver TG content and the hepatic pathology improving, and has compared certain advantage with the Western medicine Essentiale N/Essentiale Forte N; The present invention feeds at prevention MCD diet and has obvious curative effects equally aspect the NASH mice, and it can obviously reduce mice serum ALT level, liver TG content, improves the liver fat lesion degree, and no significant difference between the 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).
Description of drawings
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 to further specify 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
The above-mentioned raw materials medicine is added conventional adjuvant according to common process process granule.Every bag 10 gram, 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
The above-mentioned raw materials medicine is added conventional adjuvant according to common process process tablet.
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
The above-mentioned raw materials medicine is added conventional adjuvant according to common process process capsule.
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
The above-mentioned raw materials medicine is added conventional adjuvant according to common process process oral liquid.
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
The above-mentioned raw materials medicine is added conventional adjuvant according to common process process sustained-release dropping pill.
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
The above-mentioned raw materials medicine is added conventional adjuvant according to common process process injection.
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
The above-mentioned raw materials medicine is added conventional adjuvant according to common process process lyophilized injectable powder.
Claims (9)
1. the pharmaceutical composition of prevention or treatment non-alcoholic stellato-hepatitis is characterized in that said composition is made up of following crude drug:
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.
2. pharmaceutical composition as claimed in claim 1 is characterized in that said composition is made up of following crude drug:
The Herb Gynostemmae Pentaphylli 15 weight portion Radix Curcumaes 9 weight portion Rhizoma Atractylodis Macrocephalaes 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 Miltiorrhizaes 15 weight portion Semen Sinapis Albaes 6 weight portions
Fructus Crataegi 10 weight portions.
3. pharmaceutical composition as claimed in claim 1 is characterized in that said composition is made up of following crude drug:
The Herb Gynostemmae Pentaphylli 10 weight portion Radix Curcumaes 11 weight portion Rhizoma Atractylodis Macrocephalaes 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 Miltiorrhizaes 20 weight portion Semen Sinapis Albaes 4 weight portions
Fructus Crataegi 12 weight portions.
4. pharmaceutical composition as claimed in claim 1 is characterized in that said composition is made up of following crude drug:
The Herb Gynostemmae Pentaphylli 20 weight portion Radix Curcumaes 7 weight portion Rhizoma Atractylodis Macrocephalaes 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 Miltiorrhizaes 10 weight portion Semen Sinapis Albaes 8 weight portions
Fructus Crataegi 7 weight portions.
5. like the described pharmaceutical composition of one of claim 1-4, it is characterized in that said composition adds conventional adjuvant according to common process and processes the tablet of clinical acceptance, capsule, granule, pill, powder, oral liquid or injection.
6. like the described pharmaceutical composition of one of claim 1-4, it is characterized in that said composition adds conventional adjuvant according to common process and processes the slow releasing tablet of clinical acceptance, slow releasing capsule, sustained-release dropping pill or lyophilized injectable powder.
7. like the application of the described pharmaceutical composition of one of claim 1-4 in the medicine of prevention or treatment non-alcoholic stellato-hepatitis.
8. application as claimed in claim 7 is characterized in that said prevention or treatment non-alcoholic stellato-hepatitis are meant reduction Serum ALT, AST or TG level.
9. application as claimed in claim 7 is characterized in that said prevention or treatment non-alcoholic stellato-hepatitis are meant 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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| CN116115724A (en) * | 2023-03-30 | 2023-05-16 | 北京中医药大学 | Traditional Chinese medicine composition, pharmaceutical preparation, 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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