CN108066506A - A kind of compound medicine for treating chronic liver disease and preparation method thereof - Google Patents
A kind of compound medicine for treating chronic liver disease and preparation method thereof Download PDFInfo
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- CN108066506A CN108066506A CN201810115954.5A CN201810115954A CN108066506A CN 108066506 A CN108066506 A CN 108066506A CN 201810115954 A CN201810115954 A CN 201810115954A CN 108066506 A CN108066506 A CN 108066506A
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A61K2236/30—Extraction of the material
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- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
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Abstract
The present invention relates to a kind of compound medicines for treating chronic liver disease and preparation method thereof, the compound medicine be by medicine Tianshan Mountains violet, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, 7 taste medicinal materials of A Bole be raw material, the abundant mixing of auxiliary material is separately added into again, and mixture, oral liquid, granule, tablet, capsule or dripping pill are made using solvent extraction, removal of impurities, concentration, drying means.Drug of the present invention shows through results of animal：It is horizontal that ALT, AST in liver injury model mice serum can be reduced, mitigate hepatic injury pathological state, the scorching left back sufficient paw swelling of cause can be reduced.There is certain protective role to mouse liver injury model.The compound medicine is theoretical according to Uygur medicine, and long-term name doctor clinical practice is foundation, with reference to modern study, dissolves out its active ingredient using reasonable drawing method, enhances drug effect, improve bioavilability, provided a convenient for patient.
Description
Technical field
The present invention relates to a kind of compound medicines for treating chronic liver disease and preparation method thereof, belong to national medicine technology neck
Domain.
Background technology
Chronic liver disease includes chronic hepatitis (most of is chronic viral hepatitis type B), posthepatitic cirrhosis etc., clinical
On, liver is inflamed and necrosis of liver cells and oxyhepatitis (B-mode or the third type) protracted course of disease, and the course of disease is more than half a year can be into
It is a kind of common disease and frequently-occurring disease for chronic liver disease.If chronic liver disease continues to develop, the damage journey of hepar damnification is often increased
Degree, so as to cause liver cell inflammation, necrosis, and the pathologic process of secondary fibrosis, and liver fibrosis is even former to hepatic sclerosis
One intermediate link of Diagnosis development.Show according to statistics, China there are about 100,000,000 2 thousand ten thousand patients with chronic liver, every year there are about
300000 people because hepatopathy and its caused by complication cause death, and be even more every year to reach 300-500 for the medical expense of hepatopathy
Hundred million yuans.At present, the treatment of chronic liver disease is still a problem.Doctor trained in Western medicine includes chronic liver disease primary treatments,
Antiviral therapy (key agents have interferon, Lamivudine, Aldoforwe ester, Sebivo, grace for dimension card etc.), liver protecting therapy
(key agents have Glucurolactone, glutathione, Tiopronin, penicillamine etc.), glucocorticoid treatment etc..But clinically
The effect of drugs of application is still unsatisfactory, and its toxic side effect is larger.Uighur medicine has the understanding of hepatopathy thousands of
According to Uygur medicine theory and clinical practice, exploitation " safely, effectively, inexpensive " can be expected to reference to modern study for the history in year
The drug of novel therapeutic chronic liver disease.
Chinese patent ZL201310078943.1, a kind of compound medicine for treating chronic liver disease and preparation method thereof are China
Xinjiang physiochemical techniques research institute of the academy of sciences is multiple described in the patent according to Uygur medicine is theoretical and the previous research work of clinical practice
Prescription object is made of Artemisia capillaris, alpine yallow herb, saussurea intybus, rose, rheum officinale, 6 taste medicinal material of Radix Glycyrrhizae.The present invention by Tianshan Mountains violet,
Nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, 7 taste medicinal materials of A Bole are made, and two prescriptions are in chemical composition, medicine
There is relatively big difference in terms of effect material base and mechanism of action.Pharmacodynamic experiment is the result shows that Chinese patent
Drug described in ZL201310078943.1 reduces ALT, AST level in liver injury model mice serum, mitigates hepatic injury pathology
Symptom has protective effect to hepatic injury.And drug of the present invention reduces ALT, AST water in liver injury model mice serum
It is flat, while mitigating hepatic injury pathological state, the scorching left back sufficient paw swelling of cause can be reduced.In addition, the present invention is according to ELISA
It is bad that the method for kit measures glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminease (AST), alkaline phosphatase (ALP), tumour in serum
Necrosis factor (TNF-α), active oxygen (ROS), triglycerides (TG), T-CHOL (TC), high-density lipoprotein (HDL), low-density
Superoxide dismutase (SOD) level, malonaldehyde (MDA) level in lipoprotein (LDL) level and tissue homogenate, cytochromes
Enzyme (CYP-450) is horizontal.The result shows that drug of the present invention may be with tune to the Protective effects of mouse liver injury model
Inflammatory factor is saved, removes free radical, anti-lipid peroxidation is related.
The content of the invention
Present invention aims at provide a kind of compound medicine for treating chronic liver disease and preparation method thereof, the compound medicine
Be by Tianshan Mountains violet, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, 7 taste medicinal materials of A Bole be raw material, then respectively plus
Enter supplementary product starch, lactose, dextrin, povidone, microcrystalline cellulose, sucrose, pregelatinized starch, hydroxypropyl cellulose, magnesium stearate,
Odium stearate, vegetable oil, glycerin gelatine, Tween-80, sodium citrate, glycerine, sodium benzoate, ethylparaben, ethyl alcohol, poly- second
Glycol, sodium carboxymethyl starch, atoleine or the abundant mixing of shellac, are made of solvent extraction, removal of impurities, concentration, drying means
Mixture, oral liquid, granule, tablet, capsule or dripping pill.The compound medicine is theoretical according to Uygur medicine, and long-term name doctor is clinical
Foundation is practiced as, with reference to modern study, its active ingredient is dissolved out using reasonable drawing method, drug effect is enhanced, improves biology
Availability provides a convenient for patient.Drug of the present invention shows through results of animal：Liver injury model mouse can be reduced
Serum alt, AST are horizontal, mitigate hepatic injury pathological state, can reduce the scorching left back sufficient paw swelling of cause.Mouse Liver is damaged
Wound model has certain protective role, and Protective effects may be removed free radical, inhibit lipid mistake with adjusting inflammatory factor
It aoxidizes related.
A kind of compound medicine for treating chronic liver disease of the present invention, be by bulk pharmaceutical chemicals for violet 5-30 parts of Tianshan Mountains, sleep
5-30 parts of lotus flower, witloof are 5-30 parts sub-, 5-30 parts of Herba Euphorbiae Humifusae, 5-30 parts of rose, 10-20 parts of folium sennae, A Bole 10-20
Part, auxiliary material is starch, lactose, dextrin, povidone, microcrystalline cellulose, sucrose, pregelatinized starch, hydroxypropyl cellulose, stearic acid
It is magnesium, odium stearate, vegetable oil, glycerin gelatine, Tween-80, sodium citrate, glycerine, sodium benzoate, ethylparaben, ethyl alcohol, poly-
10-90 parts of ethylene glycol, sodium carboxymethyl starch, atoleine or shellac are made.
The preparation method of the compound medicine of the treatment chronic liver disease, follows these steps to carry out：
A, by violet 5-30 parts of the Tianshan Mountains through having screened, 5-30 parts of nymphaea tetragona, witloof be 5-30 parts sub-, 5-30 parts of Herba Euphorbiae Humifusae,
5-30 parts of rose, 10-20 parts of folium sennae, 10-20 parts of mixing of A Bole, are crushed to 10-80 mesh and powder are made；
Or by violet 5-30 parts of the Tianshan Mountains through having screened, 5-30 parts of nymphaea tetragona, witloof be 5-30 parts sub-, 5-30 parts of Herba Euphorbiae Humifusae,
5-30 parts of rose, 10-20 parts of folium sennae, 10-20 parts of A Bole are extracted 1-4 times with the 4-20 times of water measured, and temperature is boiled for solvent
Point, when each extraction time is 1 small, with ethanol precipitation, alcohol precipitation concentration 40-80%, filtering obtains extract；
Or by violet 5-30 parts of the Tianshan Mountains through having screened, 5-30 parts of nymphaea tetragona, witloof be 5-30 parts sub-, 5-30 parts of Herba Euphorbiae Humifusae,
5-30 parts of rose, 10-20 parts of folium sennae, 10-20 parts of concentration measured with 8-10 times of A Bole are 10-95% ethyl alcohol extraction 1-4
It is secondary, temperature for 30 DEG C-to solvent boiling point, each extraction time for 1-3 it is small when, obtain extract；
B, the extract recycling design that will be obtained in step a concentrates, dry, obtains dry extract, dry extract is crushed into powder
End, then supplementary product starch, lactose, dextrin, povidone are separately added into, microcrystalline cellulose, sucrose, pregelatinized starch, hydroxy propyl cellulose
Element, magnesium stearate, odium stearate, vegetable oil, glycerin gelatine, Tween-80, sodium citrate, glycerine, sodium benzoate, nipalgin second
10-90 parts of ester, ethyl alcohol, polyethylene glycol, sodium carboxymethyl starch, atoleine or shellac abundant mixings, routinely pharmaceutical methods system
Into mixture, oral liquid, granule, tablet, capsule or dripping pill.
It is of the present invention it is a kind of treat chronic liver disease compound medicine and preparation method thereof, the compound medicine is by Uygur
The common tonifying liver class of doctor, the clinical experience side that bile matter adjusts class, antipyretic and antidotal type Uygur medicine forms, prescription central Tianshan violet,
Nymphaea tetragona, which plays, reduced the bile matter contained and blood matter, adjustment liver makings, purify the blood it is logical stagnant, it is clearing heat and detoxicating, hot nourishing the liver is dropped, into
The effects that ripe exception bile matter；The heat of liver is dropped, is purified the blood logical stagnant, clearing heat and detoxicating, the effect of ripe exception bile matter；Herba Euphorbiae Humifusae, chrysanthemum
Lettuce purifies the blood toxin expelling, reduces Sheng bile matter and blood matter, opens arteries and veins resistance, eliminates jaundice, the effect of diuresis detumescence；Folium sennae, Ah
Bo Le, which rises, removes abnormal bile matter, relaxes bowel, opens obstruction, the effect of quenching the thirst of bringing down a fever reduced Sheng bile matter and blood matter, clearly
Blood toxin expelling opens arteries and veins resistance, laxative defaecation, the effect of diuresis detumescence；Rose plays inhibition bile matter and crosses Sheng, nourishes stomach, clear
Abnormal bile plastid liquid, relaxes bowel, cerebral tonic tranquillizing effect.Preparation made of the preparation method has dysregulation bile
Matter removes abnormal phlegm, drops the functions such as hot nourishing the liver, diuresis detumescence, anti-inflammatory analgetic.Curing mainly slow liver disease includes hepatitis, Huang
Subcutaneous ulcer, hepatosplenomegaly, liver have resistance etc..
It is of the present invention it is a kind of treat chronic liver disease compound medicine and preparation method thereof, the medicine that the compound medicine is selected
Material has following characteristic：
Tianshan Mountains violet：It is raw, acrid flavour.Ripe exception bile matter, reduced the bile matter contained and blood matter, clearing heat and detoxicating,
Anti-inflammatory is brought down a fever, and moistening lung detumescence, wet one's whistle cough-relieving, smoothening secretion etc..Xeothermic property or bile matter disease are cured mainly, such as fever fever is
It is diligent come it is sexy emit, the headache of xeothermic property and acute pleurisy, pneumonia, dry throat cough, the diseases such as difficulty in urination and defecation.
Nymphaea tetragona：Two level is raw, micro- light.With ripe abnormal bile matter, wet brain is calmed the nerves, and heat-clearing bushing drops hot nourishing the liver, disappears
Scorching cough-relieving, wet one's whistle the effects that quenching one's thirst.For xeothermic property or bile matter disease, such as xeothermic property brain is empty, has a guilty conscience, liver void, hot sense
It emits, dry cough, dryness of the pharynx and larynx, restlessness and thirst etc..
Witloof：It is dry cold, lightly seasoned or slight bitter.With dysregulation blood matter, liver resistance is opened, heat clearing and inflammation relieving eliminates jaundice,
Diuresis detumescence.Humid or blood matter disease are cured mainly, if liver blocks, humid hepatitis, icterepatitis, systemic water
It is swollen, difficult urination etc..
Rose：It is mild-natured.Stomach is nourished, improves digestion, resuscitation with aromatics, ataralgesia, relieve heat anti-inflammatory, soft intestines defaecation, profit
Skin blazes.Anorexia, indigestion are cured mainly, various tuberculosis cause deeline, neurasthenia, palpitaition, insomnia, dizziness
Brain is swollen, rheumatalgia pain, myocarditis, hepatitis, constipation, and appearance is pale.
Herba Euphorbiae Humifusae：Two level is done cold.With ripe abnormal bile juice, black courage matter, mucilaginous substance, dilute blood is logical stagnant, purifies the blood,
Also diuresis, Gu gum, removes abnormal humour, the effects that appetizing.For pruritus, tinea, liver and spleen obstruction, renal shutdown, gum loosening, food
It is intended to weaken, jaundice, the various diseases caused by blood is unclean.
Folium sennae：Level-one is done, two level heat, sweet in flavor, bitter.Abnormal lymphatic temperament, tonneau stool are removed, the refreshing heart pleases will, opens resistance
Plug, air-dispersing analgesic, dispelling wind and arresting itching.It cures mainly and black courage matter disease, such as habitual constipation, hysteria is penetrated into lymphatic temperament or lymphatic temperament
Disease, antimigraine is mad, neuropathy, bowel obstruction, abdominal pain and distension, rheumatoid arthritis, sciatica, coat loss, skin
Itch, acne.
A Bole：Level-one is damp and hot, sweet, slightly sour.Black courage matter is contained with removing, heat clearing and inflammation relieving relaxes bowel, and air-dispersing is led to
Through the effects that.The black various diseases of courage matter caused by burning precipitation for dry cold or body fluid, are particularly suitable for black courage matter, bile matter
The disease contained is crossed, if dryness is scorching swollen, hot eyes ophthalmodynia, bitterly, larynx does constipation, joint cusalgia, amenorrhea bellyache, dry cough asthma to intestines choke
Deng.
Description of the drawings
Fig. 1 is the present invention to CCl4The influence of hepatic injury mouse liver pathological tissue is caused, wherein 1 blank group, 2 model groups, 3
Positive drug group, 4 low dose groups, 5 middle dose groups, 6 high dose groups.
Specific embodiment
Embodiment 1
(to prepare 1000ml as radix, prepare oral liquid, enumerated in a manner of table)
Tianshan Mountains violet through having screened, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, A Bole are mixed, powder
60 mesh are broken to, are extracted 4 times with the water of 4 times of amounts, temperature is solvent boiling point, when each extraction time is 1 small, with ethanol precipitation, alcohol
Heavy concentration is 40%, filtering, recycling design, concentration, and with the abundant mixing of auxiliary material, sterilizing is canned that oral liquid is made.
Embodiment 2
(to prepare 1000ml as radix, prepare mixture, enumerated in a manner of table)
Tianshan Mountains violet through having screened, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, A Bole are mixed, powder
10 mesh are broken to, are extracted 1 time with the water of 20 times of amounts, temperature is solvent boiling point, and when extraction time is 3 small, with ethanol precipitation, alcohol precipitation is dense
It spends for 80%, filtering, recycling design, concentration, with the abundant mixing of auxiliary material, sterilizing is canned that mixture is made.
Embodiment 3
(to prepare 1000ml as radix, prepare granule, enumerated in a manner of table)
Tianshan Mountains violet through having screened, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, A Bole are mixed, powder
24 mesh are broken to, are extracted 2 times with 95% ethyl alcohol of 10 times of amounts, temperature is 30 DEG C, when each extraction time is 1.5 small, is filtered, recycling
Solvent, concentration, with the abundant mixing of auxiliary material, granulation, granule is made in whole grain.
Embodiment 4
(to prepare 1000g as radix, prepare powder, enumerated in a manner of table)
By the Tianshan Mountains violet through having screened, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, A Bole mixed powders
80 mesh are broken to, powder is made in packaging.
Embodiment 5
(to prepare 1000g as radix, prepare tablet, enumerated in a manner of table)
By the Tianshan Mountains violet through having screened, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, A Bole mixed powders
24 mesh are broken to, are extracted 2 times with 10% ethyl alcohol of 8 times of amounts, temperature is 70 DEG C, when each extraction time is 1.5 small, is filtered, recycling
Solvent concentrates, and dry, i.e., dry extract is broken into powder, and with the abundant mixing of auxiliary material, tablet is made according to a conventional method.
Embodiment 6
(to prepare 1000g as radix, prepare capsule, enumerated in a manner of table)
By the Tianshan Mountains violet through having screened, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, A Bole mixed powders
24 mesh are broken to, are extracted 2 times with 20% ethyl alcohol of 9 times of amounts, temperature is 70 DEG C, when each extraction time is 1.5 small, is filtered, recycling
Solvent concentrates, and dry, i.e., dry extract is broken into powder, and with the abundant mixing of auxiliary material, capsule is made according to a conventional method.
Embodiment 7
(to prepare 1000g as radix, prepare dripping pill, enumerated in a manner of table)
By the Tianshan Mountains violet through having screened, nymphaea tetragona, witloof, Herba Euphorbiae Humifusae, rose, folium sennae, A Bole mixed powders
24 mesh are broken to, are extracted 2 times with 50% ethyl alcohol of 8 times of amounts, temperature is 70 DEG C, when each extraction time is 1.5 small, is filtered, recycling
Solvent concentrates, and dry, i.e., dry extract is broken into powder, and with the abundant mixing of auxiliary material, dripping pill is made according to a conventional method.
Embodiment 8
It is of the present invention it is a kind of treat chronic liver disease compound medicine, compound medicine is to CCl4Cause grinding for acute liver damage
Study carefully：
1 experiment material：
1.1 experimental drug：
1.1.1 by reagent：
Title：Treatment chronic liver disease compound medicine of the present invention；
1.1.2 comparison medicine：
Title：Silybin Capsules, specification：Every 35mg containing legalon, usage and dosage：It is oral, it is grown up three times a day,
2-4 every time, authentication code：Chinese medicines quasi-word H33020822, batch number：161264, manufacturing enterprise：Tianjin day Shi Lishengte
Pharmacy stock Co., Ltd；
1.1.3 dosage is set：
Dosage installation warrants, the clinical plan provided using consigner are proportionally converted into different genera with dosage as foundation
Clinical equivalent dosage is arranged to middle dosage by the dose,equivalent of animal；
Present invention treatment chronic liver disease compound medicine is the 65g/ man days into human oral dosage form, and drug paste-forming rate is 21.1%,
1g medicinal extract is equivalent to 4.728g crude drugs, by mouse and people's dose lonvestion, is converted to mouse dose as middle dosage (300mg/Kg
My god), its 2 times are taken as high dose (600mg/Kg days), take 0.5 times as low dosage (150mg/Kg days)；
Comparison medicine：The clinical adult of the legalon oral 210mg/ man days, by mouse and people's dose lonvestion, it is converted to the positive
The mice clinical dose,equivalent of comparison medicine is 21mg/Kg days；
1 experiment packet of table is set with dosage
1.1.4 experimental drug configures：
Present invention treatment chronic liver disease compound medicine is configured in this experiment with distilled water, and concentration is from low to high：15mg/
ML, 30mg/mL and 60mg/mL, should have preferable mobility, direct gavage after the completion of configuration, positive drug places some
Perhaps precipitate, need to shake up before use, prevent drug precipitation layering from influencing the accuracy of gavage concentration；
1.2 experimental animal：
1.2.1 experimental animal strain and source：Kunming mouse, weight 25-30g, 72, male is big by Xinjiang medical courses in general
It learns Experimental Animal Center to provide, experimental animal production licence number：SCXK (new) 2016-0002, rank：SPF grades；
1.2.2 experimental animal feeding：
Every 6 cages of experimental animal, conventinal breeding, free choice feeding and drinking-water；Normal diet：It is tested by Xinjiang Medicine University
Animal center provides；Drinking-water：Drink experimental animal dedicated water；
1.2.3 experimental animal feeding environment：
Xinjiang Medicine University's Experimental Animal Center, temperature：22-25 DEG C, relative humidity：40%-60%, illumination condition：
12h/12h light and shades replace, situation of divulging information：All-fresh air；
1.3 reagents and other：
Carbon tetrachloride (Tianjin Fu Yu Fine Chemical Co., Ltd)；A Hu Ji spends pure peanut oil (Qingdao Co., Ltd)；
ELISA kit (SOD, MDA, ALT, AST, ALP, CYP-450, TNF-α, ROS) Shanghai Yu Bo Co., Ltds；Blood fat four
Co., Ltd is built up in item kit (high-density lipoprotein, low-density lipoprotein, triglycerides, T-CHOL) Nanjing；
1.4 instruments and other：
Electronic scale (Heng Xin Electronics Co., Ltd.s of Zhongshan city)；Precision balance (plum Teller-support benefit, Switzerland's production)；Constant temperature
Cultivate oscillator (Shanghai ZHICHENG Anaiytical Instrument Manufacturing Co., Ltd.)；Centrifuge (FULGOR TDL-5A) (the luxuriant and rich with fragrance just that analysis in Shanghai
Instrument Ltd.)；Enzyme micro-plate reader (Beijing Safeheart Medical Systems Ltd.)；
1.5 statistical method：
Statistics Application method carries out statistical analysis to each group of data, and measurement data is with mean+SD (x ± s)
Mark, comparison among groups are examined using t, inspection level α=0.05；
2 experimental methods and result：
2.1 experimental method：
2.1.1CCl4The foundation of inducing mouse acute liver damage animal model：
Take Kunming mouse 72,25-30g, after adaptability feeds 3d, be randomly divided into 6 groups, be respectively blank control group,
CCl4Model group, positive controls, SP low dose groups (150mg/Kg), middle dose group (300mg/Kg), high dose group (600mg/
Kg), every group 12；Positive controls give 21mg/Kg Silybin Capsules contents, and blank control group and model group are given
Volume distilled water, the daily gavage corresponding dosage drug of experimental mice 1 time, continuous 15d；Each group mouse in 2h after the last administration,
In addition to Normal group gavage isometric(al) distilled water, the equal gavage 1%CCl of each mouse of remaining each group4Peanut oil solution 5mL/Kg weight；
2.1.2 collection of specimens：
Mouse last gavage 1%CCl4After peanut oil, 16h is deprived of food but not water, eyeball is plucked and takes blood in 1.5mL centrifuge tubes,
It standing, 3000r/min centrifugation 10min separation serum, mouse is dissected according to a conventional method after putting to death, and removes complete liver organization,
It weighs and calculates liver index, take hepatic tissue about 0.5g in every mouse liver same position, with 4 DEG C of temperature, 0.9% sodium chloride is molten
10% liver tissue homogenate is made in liquid in ice bath, and 4 DEG C, 3000r/min of temperature centrifuges 10min, takes supernatant；
2.1.3 hepatic tissue pathology microsection manufacture：
In right lobe of liver away from 2cm × 4cm × 10cm fritter liver organizations are taken at edge 0.5cm, washed with 4 DEG C of physiology salts of temperature
Residual blood, filter paper are wiped dry to the greatest extent, and 10% formalin solution is fixed, paraffin embedding, section, Hematoxylin-eosin (HE) dyeing, are seen under light microscopic
Examine the morphological changes of various tissue components of hepatic tissue section；
2.1.4 index determining：
Method according to ELISA kit measures glutamic-pyruvic transaminase (ALT) in serum, glutamic-oxalacetic transaminease (AST), alkaline phosphorus
Sour enzyme (ALP), tumor necrosis factor (TNF-α), active oxygen (ROS), triglycerides (TG), T-CHOL (TC), high density fat
Albumen (HDL), low-density lipoprotein (LDL) horizontal and in tissue homogenate superoxide dismutase (SOD) level, malonaldehyde
(MDA) horizontal, cytochromes enzyme (CYP-450) level；
2.2 experimental result：
2.2.1 to the influence of serum alt and AST contents：CCl4Model group compared with blank control group, Serum ALT and
AST substantially increases (P<0.01), with CCl4Model group compares, present invention treatment each dosage group serum of chronic liver disease compound medicine
ALT, AST level reduce (P<0.05 or P<0.01), and into dose-dependence, 2 are shown in Table；
2 compound medicine of the present invention of table is to CCl4Cause the ALT of acute hepatic injury mice serum, the influence of ASL
Note：Compared with blank group△△P<0.01；The * P compared with model group<0.05,**P<0.01；
2.2.2 serum alkaline phosphatase (ALP) content is influenced：CCl4Model group is compared with blank control group, serum
ALP substantially increases (P<0.01), with CCl4Model group compares, each dosage group serum alkaline phosphatase of compound medicine of the present invention
(ALP) it is horizontal to be substantially reduced (P<0.01), and into dose-dependence, 3 are shown in Table；
3 compound medicine of the present invention of table is to CCl4Cause the influence of the ALP of acute hepatic injury mice serum
Note：Compared with blank group△△P<0.01；The * * P compared with model group<0.01；
2.2.3 to CCl4Cause the influence of the inflammatory factor expression of acute liver damage：CCl4Model group and blank control group ratio
Compared with TNF-α level substantially increases (P in serum<0.01), with CCl4Model group compares, each dosage group serum of compound medicine of the present invention
TNF-α level is substantially reduced (P<0.01), and into dose-dependence, 4 are shown in Table；
4 compound medicine of the present invention of table is to CCl4Cause the influence of the TNF-α of acute hepatic injury mice serum
Note：The △ △ P compared with blank group<0.01；The * * P compared with model group<0.01；
2.2.4 to the influence of malonaldehyde in hepatic tissue (MDA) and superoxide dismutase (SOD) content：CCl4Model group
Compared with blank control group, malonaldehyde (MDA) content increases in hepatic tissue, and superoxide dismutase (SOD) activity reduces (P<
0.05), with CCl4Model group compares, and compound medicine of the present invention is high, middle dose group can be substantially reduced in hepatic injury murine liver tissue
MDA contents wherein compound medicine high dose group of the present invention can increase the activity of superoxide dismutase (SOD), are shown in Table 5；
5 compound medicine of the present invention of table is to CCl4Cause the SOD of acute hepatic injury mice hepatic tissue, the influence of MDA contents
Note：Compared with blank group△P<0.05；The * P compared with model group<0.05,**P<0.01；
2.2.5 to the influence of active oxygen in hepatic tissue (ROS) and CYP-450 contents：CCl4Model group and blank control group
Compare, active oxygen (ROS) contents level increases (P in hepatic tissue<0.05), to cytochromes enzyme (CYP-450) activity without apparent
Change, with CCl4Model group compares, and the high, medium and low dosage group of compound medicine of the present invention can be substantially reduced hepatic injury murine liver tissue
Middle active oxygen (ROS) content (P<0.01), but to cytochromes enzyme (CYP-450) activity without substantially changeing, 6 are shown in Table；
6 compound medicine of the present invention of table is to CCl4Cause the ROS of acute hepatic injury mice hepatic tissue, the influence of CYP-450 contents
Note：Compared with blank group△P<0.05；The * * P compared with model group<0.01；
2.2.6 compound medicine of the present invention is to CCl4Cause the influence of hepatic injury mouse liver pathological tissue：Finding of naked eye：Blank pair
A bronzing is presented according to group liver, and quality is soft and high resilience；The liver volume of model group significantly increases, and matter is crisp, and surface is in micro- Huang
Color；Each dosage group of compound medicine of the present invention, positive drug group liver size and the equal boundary of color are between model group and blank control group；
Light microscopic finding：Blank group：Lobuli hepatis structure is normal, clear, cell arrangement is neat, uniform in size, central vein and sinus hepaticus are visible
Extravasated blood, portal area meet acute liver damage without significant change, remaining each group lesion；Each dosage of compound medicine of the present invention is visible：Liver
Leaflet structure exists, liver cell oedema, puts focal necrosis, it is seen that central vein, sinus hepaticus expansion extravasated blood, portal area has no apparent fibre
Dimensional tissue hyperplasia；Model group：Lobuli hepatis structure exists, liver cell oedema, puts focal necrosis, it is seen that central vein, sinus hepaticus expansion
Extravasated blood, portal area have no apparent proliferation of fibrous tissue, emphasis visible hepatolysis necrosis (diffusivity, multifocal necrosis, necrosis
Mostly since centrilobular), each group performance weight differs, and sees Fig. 1.The experimental results showed that each dosage of compound medicine of the present invention
Mitigate liver organization pathology to a certain degree to sexually revise.
Embodiment 9
The acute foot of drug Carrageenan cause of the present invention opens up the research of swelling：
1 experiment material
1.1 experimental drug
1.1.1 by reagent
Title：Treatment chronic liver disease compound medicine of the present invention；
1.1.2 comparison medicine：
Title：Dexamethasone acetate tablets, specification：0.75mg x100 pieces, usage and dosage：Starting dose be grown up as once
0.75-3.00mg (1-4 pieces), 2-4 times on the one, maintenance dose 0.75mg (1) on the about one, depending on the state of an illness；
Authentication code：Chinese medicines quasi-word H33020822, batch number：161264, manufacturing enterprise：Zhejiang celestial being jade pendant pharmacy share
Co., Ltd；
1.1.3 dosage is set：
Dosage installation warrants using clinical plan with dosage as foundation, are proportionally converted into the equivalent agent of different genera animal
Amount, middle dosage is arranged to by clinical equivalent dosage；
Compound medicine of the present invention is the 65g/ man days into human oral dosage form, and drug paste-forming rate is equivalent to for 21.1%, 1g medicinal extract
4.728g crude drugs by rat and people's dose lonvestion, are converted to rat dosage as middle dosage (300mg/Kg days), take its 2 times
As high dose (600mg/Kg days), its 0.5 times is taken as low dosage (150mg/Kg days)；
The clinical adult of the dexamethasone acetate tablets oral 4.5mg/ man days, by rat and people's dose lonvestion, it is converted to the positive
The rat clinical equivalent dosage of comparison medicine is 0.5mg/Kg days；
7 experiment packet of table is set with dosage
1.1.4 experimental drug configures：
Compound medicine of the present invention is generally configured in this experiment with distilled water, and concentration is from low to high:15mg/mL、30mg/
ML, 60mg/mL, should have preferable mobility, direct gavage after the completion of configuration, positive drug is placed with slight precipitate, needs
It shakes up before use, prevents drug precipitation layering from influencing the accuracy of gavage concentration；
1.2 experimental animal：
1.2.1 experimental animal strain and source：
Compound medicine rat of the present invention, weight 150-20g, 72, male and female half-and-half, by Xinjiang Medicine University's Experimental Animal Center
It provides, experimental animal production licence number：SCXK (new) 2016-0002, rank：SPF grades；
1.2.2 experimental animal feeding：
Every 6 cages of experimental animal, conventinal breeding, free choice feeding and drinking-water；Normal diet：By Xinjiang Medicine University animal
Center provides；Drinking-water：Drink experimental animal dedicated water；
1.2.3 experimental animal feeding environment：
Xinjiang Medicine University's Experimental Animal Center, temperature：22-25 DEG C, relative humidity：40%-60%, illumination condition：
12h/12h light and shades replace, situation of divulging information：All-fresh air；
1.3 reagents and other：
Carrageenan (Sigma, the U.S.)；
1.4 instruments and other：
Electronic scale (Heng Xin Electronics Co., Ltd.s of Zhongshan city), precision balance (plum Teller-support benefit, Switzerland's production), PV-
200 toes cubic content measurement instrument (Chengdu TME Technology Co., Ltd.), (analytical instrument manufacture in Shanghai intelligence city has constant temperature culture oscillator
Limit company)；
1.5 statistical method
Statistics Application method carries out statistical analysis to each group of data, and measurement data is with mean+SD
Mark, comparison among groups are examined using t, inspection level α=0.05；
2 experimental methods and result：
2.1 experimental method：
Healthy SD rat is taken, weight 150-200g, male and female are half-and-half.Adaptability feeds 3d, is randomly divided into blank group, positive drug
Dexamethasone acetate group (0.5mg/Kg days), the basic, normal, high dosage group of compound medicine of the present invention (be respectively 150,300,600mg/
Kg days), continuous gavage is administered 7 days, and wherein blank group, model group gives corresponding distilled water gavage, is administered in the 8th day
After 30min, in addition to blank group, in left side toes portion injection carrageenan 0.1mL/ only, right foot is control to remaining each rat, in note
It penetrates rear 2h, 4h, 6h and measures the volume of rat toes and the ankle portion that arrives, and its swelling is calculated with following equation：Swelling=
(left foot opens up volume-right sufficient control group and opens up volume enough enough)/right sufficient control group opens up volume × 100% enough；
2.2 experimental result：
Rat paw edema degree is with the result for causing scorching time change：After the left back whole foot plantar injection carrageenan of rat with
Its swelling degree of the paw of the variation of time also has occurred corresponding variation, injects 2h after carrageenan, model group cause scorching left back foot with
Relatively, paw swelling is apparently higher than itself right metapedes control group (P for itself right metapedes control foot<0.01), in SP, low dose group is equal
It can reduce and cause scorching left back sufficient paw swelling (P<0.05), high dose group is apparent can reduce the scorching left back sufficient paw swelling (P of cause<
0.01)；4h after injection carrageenan, model group causes scorching left back foot, and paw swelling is apparently higher than certainly compared with right metapedes control foot
The right metapedes control group (P of body<0.01), compound medicine of the present invention is high, middle dose group is equal can reduce the scorching left back sufficient paw swelling (P of cause<
0.01)；6h after injection carrageenan, over time, model group and each dosage group of compound medicine of the present invention cause scorching left back foot
Gradually tend to recover normal, it is not statistically significant, it is shown in Table 8；
8 compound medicine Carrageenan of the present invention of table cause rat opens up the influence of swelling enough
Note：The * P compared with model group<0.05, * * P<0.01.
Claims (2)
1. a kind of compound medicine for treating chronic liver disease, it is characterised in that be by bulk pharmaceutical chemicals for violet 5-30 parts of Tianshan Mountains, nymphaea tetragona
5-30 parts, witloof is 5-30 parts sub-, 5-30 parts of Herba Euphorbiae Humifusae, 5-30 parts of rose, 10-20 parts of folium sennae, 10-20 parts of A Bole is auxiliary
Expect for starch, lactose, dextrin, povidone, microcrystalline cellulose, sucrose, pregelatinized starch, hydroxypropyl cellulose, magnesium stearate, hard
Resin acid sodium, vegetable oil, glycerin gelatine, Tween-80, sodium citrate, glycerine, sodium benzoate, ethylparaben, ethyl alcohol, poly- second two
10-90 parts of alcohol, sodium carboxymethyl starch, atoleine or shellac are made.
2. the preparation method of the compound medicine for the treatment of chronic liver disease according to claim 1, it is characterised in that by following step
It is rapid to carry out：
A, by violet 5-30 parts of the Tianshan Mountains through having screened, 5-30 parts of nymphaea tetragona, witloof be 5-30 parts sub-, 5-30 parts of Herba Euphorbiae Humifusae, rose
Flower 5-30 parts, 10-20 parts of folium sennae, 10-20 parts of mixing of A Bole, are crushed to 10-80 mesh and powder are made；
Or by violet 5-30 parts of the Tianshan Mountains through having screened, 5-30 parts of nymphaea tetragona, witloof be 5-30 parts sub-, 5-30 parts of Herba Euphorbiae Humifusae, rose
Flower 5-30 parts, 10-20 parts of folium sennae, 10-20 parts of A Bole are extracted 1-4 times with the 4-20 times of water measured, and temperature is solvent boiling point, often
When secondary extraction time is 1 small, with ethanol precipitation, alcohol precipitation concentration 40-80%, filtering obtains extract；
Or by violet 5-30 parts of the Tianshan Mountains through having screened, 5-30 parts of nymphaea tetragona, witloof be 5-30 parts sub-, 5-30 parts of Herba Euphorbiae Humifusae, rose
Flower 5-30 parts, 10-20 parts of folium sennae, 10-20 parts of concentration measured with 8-10 times of A Bole are that 10-95% ethyl alcohol extracts 1-4 times, temperature
Spend for 30 DEG C-to solvent boiling point, each extraction time for 1-3 it is small when, obtain extract；
B, the extract recycling design that will be obtained in step a concentrates, dry, obtains dry extract, dry extract is broken into powder,
Be separately added into supplementary product starch, lactose, dextrin, povidone again, microcrystalline cellulose, sucrose, pregelatinized starch, hydroxypropyl cellulose,
Magnesium stearate, odium stearate, vegetable oil, glycerin gelatine, Tween-80, sodium citrate, glycerine, sodium benzoate, ethylparaben,
10-90 parts of ethyl alcohol, polyethylene glycol, sodium carboxymethyl starch, atoleine or shellac abundant mixings, routinely pharmaceutical methods conjunction is made
Agent, oral liquid, granule, tablet, capsule or dripping pill.
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| CN103830379A (en) * | 2014-03-03 | 2014-06-04 | 新疆吐鲁番地区维吾尔医医院 | Blood purifying mixture for treating skin diseases |
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