CN104758796B - Treat medicine of hepatic sclerosis and preparation method thereof - Google Patents
Treat medicine of hepatic sclerosis and preparation method thereof Download PDFInfo
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- CN104758796B CN104758796B CN201410801986.2A CN201410801986A CN104758796B CN 104758796 B CN104758796 B CN 104758796B CN 201410801986 A CN201410801986 A CN 201410801986A CN 104758796 B CN104758796 B CN 104758796B
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Abstract
The invention discloses a kind of medicine for treating hepatic sclerosis and preparation method thereof, the described medicine is made up of following weight than component：Golden-rimmed leech 10 60, curcuma zedoary 20 80, giant knotweed 10 50, false-yellowflower milkwort root or herb 4 35, Radix Angelicae Sinensis 4 30, rhizoma alismatis 5 30, Sculellaria barbata 5 40 and Soil unit 5 80.The medicine all medicines share of the present invention, Tong Longlu Huo Lu, solve disease due to noxious agents produced by various parasites, except wet poison, waterway, tune fill blood, therefore sick self-healing.
Description
Technical field
The present invention relates to a kind of medicine for treating hepatopathy.It is more particularly related to have to treatment hepatic sclerosis aobvious
Write medicine of curative effect and preparation method thereof.
Background technology
Hepatic sclerosis is a kind of very common chronic, diffusivity, progressive fibrous lesions, can be by one or more former
Cause, or liver damage caused by other unknown causes.The necrosis of liver cell diffusivity is embodied in, proliferation of fibrous tissue occurs
Regenerated with liver cell nodules shape, these three change staggeredly is carried out repeatedly, as a result the gradual quilt of lobuli hepatis structure and blood circulation path
Reconstruction, makes liver be hardened and causes hepatic sclerosis.Have no specific treatment method at present.
The cause of disease key of hepatic sclerosis is the dysfunction of liver,spleen,kidney.Stagnation of liver qi, the stagnation of the circulation of vital energy cause train of thought obstruction to be to be formed
One Fundamentals of hepatic sclerosis.Next to that spleen function is damaged, transformation failure of spleen causes that water is wet to stop gathering then.Furthermore exactly kidney
Gasification function is damaged, it is impossible to an important factor for evaporating retention of water-damp, and forming expansion.In irritability stasis, blood-vessel obstructive, water are wet
It being the three important pathological changes to form expansion to stop.
Traditional Chinese medicine thinks that this disease belongs to " expansion " category, is named because belly swells such as drum.Being swollen with belly, color of the leather is greenish yellow,
The very then blue or green exposure of abdomen skin, four limbs pneumonedema or micro- swell are characterized.Theory of traditional Chinese medical science thinks hepatic sclerosis more because food and drink does not save, and feelings will is hindered,
Infect blood fluke, labor is intended to excessively and jaundice accumulation mistake is controlled, and makes liver,spleen,kidney functional disturbance, gas, blood, water stasis of blood product in abdomen and
Into.
Western medicine thinks that hepatic sclerosis is that infringement of many factors to liver cell is the chronic disease mainly showed.Liver is hard for various countries
The cause of disease of change is not quite similar, American-European more with alcoholic cirrhosis, and China is the most normal with hepatic sclerosis caused by virus hepatitis
See.
The cause of disease of China's hepatic sclerosis mainly has at present：1), virus hepatitis：Hepatic sclerosis is at me as caused by virus hepatitis
State occupy the first.The patient with liver cirrhosis hepatitis b surface antigen positive of China about 70%, 82% patient had B-mode liver in the past
Scorching virus infection；2), snail fever：Domestic scholars research finds that chronic schistosomiasis often causes the pathology of liver fibrosis to change
Become, and advanced schistosomiasis then has hepatic sclerosis；3), alcoholism：Alcoholism is the main cause of American-European hepatic sclerosis, concurrent hepatitis B sense
Dye meeting co-solvents hepatopathy, is more easily caused hepatic sclerosis；4), toxic cirrhosis of liver：Hepatic sclerosis caused by medicine or chemical toxicant,
Such as carbon tetrachloride, methotrexate (MTX)；5), other：Disease of biliary tract, vena hepatica backflow obstruction, hereditary metabolic disorders, congenital plum
Poison, autoimmune disease, dystrophia and hepatic sclerosis caused by other unknown causes.
The therapeutic modality of hepatic sclerosis mainly uses liver protection, support and ascites treating at present, while coordinates portal hypertension
The processing of operative treatment and complication；The medicine of hepatic sclerosis is various in style simultaneously, is broadly divided into three major types：The first kind is
Antiviral drugs, this medicine have two kinds, and one kind is interferon, and another kind is nucleoside analog；Second class is to treat hepatic sclerosis simultaneously
Disease drug is sent out, there is anti-liver ascites, also have anti-alimentary tract bleeding and anti-hepatic encephalopathy；3rd class is liver protection and anti-fibrosis
Medicine, these medicines are presently mainly some Chinese patent drugs.But clinically these medicines have certain curative effect, but actual efficacy is but
It is limited because of a variety of causes.
How to produce a kind of specific drug for hepatic sclerosis, can effectively play Tong Longlu Huo Lu, solution disease due to noxious agents produced by various parasites, except wet poison,
Waterway, the effect that fills blood of tune, the problem of this is urgent need to resolve.
The content of the invention
As the result of various extensive and careful research and experiment, it has been found by the inventor that in medicine
Golden-rimmed leech, salty, bitter, flat, Tiao Long roads, the scattered stasis of blood swells；Soil unit, salty, cold, Tong Longlu, blood stasis dispersing and deswelling analgesic；Curcuma zedoary, peppery, bitter,
Temperature, Tiao Longluhuo roads, detumescence pain, three medicines share, and are altogether Tong Longlu fire road, disperse blood stasis and dredge collateral, swelling and pain relieving；Rhizoma alismatis, sweet tea, tremble with fear, remove
Wet poison waterway, above four traditional Chinese medicine are the main ingredient in side；Sculellaria barbata, peppery, bitter, cold, heat-clearing poison, solution disease due to noxious agents produced by various parasites, waterway, logical dragon
Road；False-yellowflower milkwort root or herb, sweet tea, cold, tonifying Qi void, waterway；Radix Angelicae Sinensis, sweet tea, peppery, warm, void of enriching blood, three tastes are to help medicine；All medicines share,
Tong Longlu Huo Lu, solve disease due to noxious agents produced by various parasites, except wet poison, waterway, tune fill blood, therefore sick self-healing.Based on this discovery, the present invention is completed.
To reach above-mentioned purpose, the present invention provides a kind of medicine for treating hepatic sclerosis, and the described medicine is by following weight ratio
Component forms：Golden-rimmed leech 10-60, curcuma zedoary 20-80, giant knotweed 10-50, false-yellowflower milkwort root or herb 4-35, Radix Angelicae Sinensis 4-30, rhizoma alismatis 5-30,
Sculellaria barbata 5-40 and Soil unit 5-80.
Preferably, the described medicine is made up of following weight ratio ingredient：Golden-rimmed leech 12-18, curcuma zedoary 26-40, giant knotweed
16-22, false-yellowflower milkwort root or herb 8-25, Radix Angelicae Sinensis 7-16, rhizoma alismatis 10-18, Sculellaria barbata 6-15 and Soil unit 8-16.
Preferably, golden-rimmed leech, curcuma zedoary, giant knotweed, false-yellowflower milkwort root or herb, Radix Angelicae Sinensis, rhizoma alismatis, Sculellaria barbata and the Soil unit are with carrying
Thing is taken to replace.
Preferably, the formulation of the medicine is：Capsule, tablet, pill, drops, sustained release tablets, soft capsule, granule,
Powder, lozenge, soft extract, oral agents, syrup, ointment or plastics.
The present invention also provides a kind of method for preparing treatment hepatic sclerosis medicine, and this method comprises the following steps：
1) extraction of golden-rimmed tickclover herbal extract：Take golden-rimmed leech all, be ground into coarse powder, at a temperature of 2~20 DEG C with 6~
The saline sook coarse powder 10-13h of 10 times of amounts, filtered fluid, collect filtrate；
Add 10~40% trichloroacetic acids in the filtrate of collection so that filtrate PH is 2-3, is precipitated with centrifuge, is collected
Supernatant, by supernatant ultrafilter ultrafiltration, filtrate freeze-dried acquisition extract again；
2) extraction of curcuma zedoary, giant knotweed, false-yellowflower milkwort root or herb, Radix Angelicae Sinensis, rhizoma alismatis, Sculellaria barbata and Soil unit extract：Add 6~12 times of amounts
Water, twice, time first time is 35-45min for boiling, and second of time is 25-35min, after decoction is stood, takes its supernatant
Concentration, alcohol precipitation, then supernatant is taken, dry cream is condensed into, obtains the extract of this seven flavor medicine, extraction the rate of extract of wherein these medicines is
8-12%；
3) the extract 50-70g of golden-rimmed leech and the extract mixtures 190-220g of seven flavour of a drug, supplementary product starch 140- are taken
160g is mixed, and 1000-1200 grain capsules are made；
Prepare the medicine of the treatment hepatic sclerosis according to any one of claim 1-4.
The present invention comprises at least following beneficial effect：Golden-rimmed leech in the medicine of the present invention, salty, bitter, flat, Tiao Long roads,
The scattered stasis of blood swells；Soil unit, salty, cold, Tong Longlu, blood stasis dispersing and deswelling analgesic；Curcuma zedoary, peppery, bitter, warm, Tiao Longluhuo roads, detumescence pain, three medicines close
With being altogether Tong Longlu fire road, disperse blood stasis and dredge collateral, swelling and pain relieving；Rhizoma alismatis, sweet tea, tremble with fear, except wet poison waterway, above four traditional Chinese medicine is in side
Main ingredient；Sculellaria barbata, peppery, bitter, cold, heat-clearing poison, solution disease due to noxious agents produced by various parasites, waterway, Tong Longlu；False-yellowflower milkwort root or herb, sweet tea, tremble with fear, tonifying Qi is empty, logical
Water channel；Radix Angelicae Sinensis, sweet tea, peppery, warm, void of enriching blood, three tastes are to help medicine；All medicines share, Tong Longlu Huo Lu, solve disease due to noxious agents produced by various parasites, except wet poison, water flowing
Road, tune fill blood, therefore sick self-healing.
Brief description of the drawings
Fig. 1 is that the medicine of present invention treatment hepatic sclerosis causes the influence of hepatic injury murine liver tissue pathological change to D-GalN；
A. control group；B. model group；C. drug extract 0.97gkg-1 groups of the present invention；D. drug extract of the present invention
1.945gkg-1 groups E. drug extract 3.88gkg-1 groups of the present invention.
Embodiment
The present invention is described in further detail below in conjunction with the accompanying drawings, to make those skilled in the art with reference to specification text
Word can be implemented according to this.
It should be appreciated that such as " having ", "comprising" and " comprising " term used herein do not allot one or more
The presence or addition of individual other elements or its combination.
For the ease of the understanding of those skilled in the art, with reference to embodiment, the present invention is further illustrated, real
The content that the mode of applying refers to not is limitation of the invention.
Embodiment 1：
Medicine of the present invention makes the prescription and technique of capsule：
The extraction of golden-rimmed tickclover herbal extract：Take golden-rimmed leech all, be ground into coarse powder, at a temperature of 2~20 DEG C with 6~
The saline sook coarse powder 12h of 10 times of amounts, filtered fluid, collect filtrate；
Add 10~40% trichloroacetic acids in the filtrate of collection so that filtrate PH is 2.5, is precipitated with centrifuge, is collected
Supernatant, by supernatant ultrafilter ultrafiltration, filtrate freeze-dried acquisition extract again；
The extraction of curcuma zedoary, giant knotweed, false-yellowflower milkwort root or herb, Radix Angelicae Sinensis, rhizoma alismatis, Sculellaria barbata and Soil unit extract：Add 6~12 times amount
Water, twice, time first time is 40min for boiling, and second of time is 30min, after decoction is stood, takes its supernatant concentration, alcohol
It is heavy, then supernatant is taken, dry cream is condensed into, obtains the extract of this seven flavor medicine, wherein extraction the rate of extract of these medicines is 8-12%；
The extract 66g of golden-rimmed leech and the extract mixtures 206g of seven flavour of a drug are taken, supplementary product starch 150g is mixed, is made
1000 capsules.
Embodiment 2：
Pharmaceutical composition of the present invention makes the prescription and technique of tablet：
Extracting method is same as above, and tablet technique is：The flavour of a drug extract of golden-rimmed leech extract, giant knotweed etc. seven is taken, with hydroxypropyl
Cellulose is adhesive, softwood processed, is pelletized, and is dried, whole grain, tabletting.
Embodiment 3：
Make the prescription and technique of dripping pill：
Extracting method is same as above, and is made dropping pill technique and is：Taking polyethylene glycol 6000 is intended to dissolve by heating in 90 DEG C of oil, adds gold
Side leech extract, earth-worm extractive as raw material, the Radix Astragali and Soil unit extract, stir it is molten after move in receiver, be incubated under the conditions of 80 DEG C.
Dropping liquid valve is adjusted, pelletization in 10-15 DEG C of atoleine is instilled, dripping pill is drained, is drying to obtain.
For the present invention using the preparation technique of existing field of medicaments, above-mentioned composition can be made to various suitable clinics should
Pharmaceutical dosage form：
The pharmaceutical composition of the present invention shows that its experiment and result are as follows through pharmacodynamic study：
Material and instrument：
Medicine and reagent drug extract of the present invention are sepia dried cream powders, lot number 140401.Clinical oral administration recommends dosage
For everyone (adult) daily 5.83g dried cream powders, adult's body weight is calculated by 60kg, and it is 0.09716g dried cream powders/kg to convert into dosage
BW.Required concentration is made into during experiment with distilled water to use.Carbon tetrachloride (CCl4), Beijing Chemical Plant's product；D-Gal
(D-GalN), Beijing Suo Laibao Science and Technology Ltd product.ALT (ALT) kit, lot number 20140701；
Aspartate amino transferase (AST) kit, lot number 20140625；Total bilirubin (TBIL) kit, lot number
20140704；Total protein (TP) kit, lot number 20140703；Albumin (ALB) kit, lot number 20140610, by south
Bioengineering Research Institute's offer is built up in capital.Hyaluronic acid (HA) enzyme-linked immunoassay kit, laminin (LN) is enzyme-linked exempts from
Epidemic disease assay kit, type III precollagen (PC-III) enzyme-linked immunoassay kit, IV Collagen Type VIs (C-IV) enzyme linked immunological point
Analyse kit, Beijing Ke Yingmei Science and Technology Ltd.s product.Remaining reagent is that domestic analysis is pure.
Experimental animal Kunming mouse, male and female half and half, sub-cage rearing；SD rats, male and female half and half, sub-cage rearing, by wide
Western medical university's Experimental Animal Center provides, credit number：SCXK osmanthus 2009-0002.Raise in 20~25 DEG C, relative humidity 60
In ± 10% environment, pellet is fed, free water.
The type grating spectrophotometer of instrument 722 (Shanghai analytical instrument factory)；BS224S types electronic balance (Beijing Sai Duoli
This)；Sw-261-79 types electric heating constant-temperature water-bath tank (Shanghai Medical Apparatus and Instruments Factory)；JT75-2 type water isolation type constant incubators (Yuyao county
Insulating box factory)；SM-3 types automation enzyme non-analysis meter (day stone medical supplies in Beijing make institute).
Test method and result
The influence of acute liver is caused to D-GalN
Healthy mice 50 is taken, is randomly divided into 5 groups, every group 10, respectively Normal group, model group, medicine of the present invention
The high, medium and low dosage group of thing extract (3.88,1.94,0.97gkg-1), difference gastric infusion, 1 time/d, administered volume
20mLkg-1, Normal group and the isometric distilled water of model group gavage, continuous 10d.After last dose 1h, except normal
Control group is given outside isometric physiological saline, and D-GalN 700mgkg-1 are injected intraperitoneally in remaining each group, and water is can't help in fasting,
Mouse plucks eyeball and takes blood after 24h, centrifugation, separates serum, and ALT and AST activity is detected by kit method.A liver left side is taken after blood sampling
One fritter hepatic tissue of leaf same area is fixed in 10% formalin solution, carries out routine pathology section, HE dyeing, Jing Xiaguan
Examine pathological change.It the results are shown in Table 1 and Fig. 1.
1 drug extract of the present invention of table causes acute hepatic injury mice Serum ALT, AST influence (x ± s, n to D-GalN
=10)
Compared with model group, * P ＜ 0.05, * * P ＜ 0.01, similarly hereinafter
As a result show, the middle and high dosage of drug extract of the present invention can obviously reduce mice serum ALT levels, medicine of the present invention
Thing extract high dose also can obviously reduce mice serum AST level, and its difference has statistical significance (compared with model group
P ＜ 0.05).Visible Normal group mouse liver cell is arranged radially centered on central vein under light microscopic, lobuli hepatis knot
Structure is complete, liver cell have no denaturation,
Necrosis., locally there is spotty necrosis, with inflammatory in a large amount of liver cell oedema in D-GalN model group mouse lobuli hepatis
Cellular infiltration.Drug extract high dose group part of hepatocytes oedema of the present invention, accidental inflammatory cell infiltration, has no spotty necrosis
Stove.In drug extract of the present invention, low dose group liver cell oedema it is obvious, spotty necrosis stove is dispersed in, with inflammatory cell infiltration.
See Figure 1A~E.Drug extract of the present invention acute liver damage to caused by D-GalN is prompted to have certain protective effect.
The influence of rat liver fibrosis is caused to CCl4
Rat 50 is taken, random point of 5 groups, i.e. blank control group, model group, the high, medium and low dosage of drug extract of the present invention
Group (3.88,1.94,0.97gkg-1), every group 10.Administration group and model group rats intraperitoneal injection 40%CCl4 vegetable oil are molten
Liquid, 2 times a week, continuous 8 weeks.Modeling is administered simultaneously a group beginning ig administrations, and model group and blank control group give isometric distillation
Water, 1 time/d, continuous 8 weeks.The fasting 20h after last gavage, put to death after abdominal aortic blood, centrifuge, serum is separated, by reagent
Cassette method detects ALT, AST, TBIL, TP, ALB.It the results are shown in Table 2.
Influence (x ± s, n=of 2 drug extract of the present invention of table to CCl4 liver fibrosis due rat blood serum biochemical indicators
10)
As a result show, biochemical indicator of the drug extract high dose group of the present invention to CCl4 liver fibrosis due rat blood serums
ALT/UL-1 AST/UL-1 TBIL/ μm olL-1 have a significant effect, statistically significant (compared with the model group P of difference
＞ 0.05).Drug extract of the present invention is prompted to cause rat liver fibrosis to have certain effect CCl4.
Result of the test is summarized
Respectively with 0.97,1.94,3.88g dried cream powders/kg BW (be respectively equivalent to human body recommended amounts 5,10,20 times) dosage
Drug extract of the present invention give D-Gal (D-GalN) cause acute hepatic injury model mouse gavaging 10d, medicine of the present invention
The middle and high dosage of thing extract can obviously reduce mice serum ALT levels, and drug extract high dose of the present invention also can obviously reduce
Mice serum AST level.Pathological examination results show that drug extract of the present invention can obviously improve D-GlaN and cause Mouse Liver thin
Born of the same parents' denaturation, the scope and degree of necrosis, reduce inflammation cellular infiltration degree.Respectively with 0.97,1.94,3.88g dried cream powders/kg
The drug extract of the present invention of BW dosage gavages 8 weeks to carbon tetrachloride (CCl4) liver fibrosis due rat model, medicine of the present invention
Extract high dose group has necessarily to the biochemical indicator ALT/UL-1 AST/UL-1 TBIL/ μm olL-1 of rat blood serum
Influence.Prompt drug extract of the present invention acute liver damage to caused by D-GalN to have certain protective effect, CCl4 is caused big
Liver fibrosis also has certain effect.
Pharmaceutical composition acute toxicological experiment of the present invention：
Test medicine：Pharmaceutical composition of the present invention, make lot number：20140301.Every gram of the pharmaceutical composition of the present invention contains
11.49 grams of medicinal material.Every capsule 4.47g containing crude drug, adult dosage 3 times a day, daily 15.Because of dose relationship, this experiment uses it
Dried cream powder is administered, and every gram of powder contains 11.49 grams of medicinal material.Before experiment 0.7g powder/ml (Cmaxs, with irrigation stomach device are made into distilled water
Can aspirate as degree) it is for experiment.
Animal subject：KM mouse, body weight 19-22g, male and female half and half, provided by Guangxi Medical University's Experimental Animal Center
(SCXK osmanthus 2003-0003).
Test method：Trial test 40ml/kg administration animals all survive, and do not detect LD50, therefore carry out maximum dosage-feeding examination
Test.KM mouse 40 separately are taken, if administration group and each 20 of control group, male and female half and half.Sex is divided to raise, after fasting 12h, administration group
It is administered 3 times, each 40ml/kg to mouse stomach in one day, is spaced 4h, control group is with method to distilled water.Animal is raised with particulate material
Support, free water, 24-26 DEG C of room temperature, relative humidity 60%, observe the general activity situation of animal in two weeks after administration according to following table
And survival condition.
Table：Animal acute toxicity test observes table
Result of the test：After the administration of administration group mouse without excitement, uneasiness, play, jump, erect hair, shed tears, salivate, convex eye, torsion
Precursor reactant phenomenon.Observation 14 days, all animals survival.Mouse is put to death after weighing within 15th day, dissection finds gastric filling, and intestines are without swollen
Gas.Dissection visually observes the heart, liver, spleen, lung, kidney, adrenal gland, thymus gland, ovary, uterus, brain, lymph node, testis, stomach, intestines and chest
Chamber, abdominal cavity, each organ mass, color and quality are without exception.Body weight is 20.1 ± 1.29g before administration group administration, the 14th day body
Weight is 24.4 ± 1.19g.Body weight is 19.95 ± 1.15g before control group administration, and the 14th day body weight is 24.6 ± 1.69g.Items refer to
Administration group is marked compared with control group without significant difference.
This experiment mice dosage is dried cream powder 84g/kg, that is, medicinal material 965.2g/kg body weight.
Conclusion：The pharmaceutical composition mouse stomach administration of the present invention does not detect LD50, maximum dosage-feeding be 965.2g medicinal materials/
Kg, equivalent to 864 times of Coming-of-Age Day plan dosage, have no toxic reaction.
The preclinical experience of pharmaceutical composition hepatic sclerosis of the present invention：
Over more than 10 years, using many cases hepatic sclerosis of medicine composite for curing 100 (compensatory phase) patient of the present invention, tcm diagnosis is
Product card (stagnation of the circulation of vital energy blood hinder and type of blood-stasis obstructing in the interior), card be turgor under right flank, pain, it is fixed do not move, diet is reduced, it is swollen to make after food, or
Stomach wall train of thought anger, dim black, the bitter taste dry of complexion, morbid amenorrhea, impotence in male, tongue nature is livid purple or ecchymosis, liver function and B ultrasound
Inspection, which meets, is diagnosed as hepatic sclerosis.After drug therapy of the present invention 3 months to 1 year, the symptom and liver function of patient, ultrasound diagnosis,
Some is clearly better, efficient to be fully recovered up to more than 95%, 30% patient.
3 months long term toxicity tests of pharmaceutical composition of the present invention
Medicine of the present invention (is respectively equivalent to clinical daily dose 1.117g medicines with 134g, 67g, 33.5g medicinal material/kg/d respectively
120 times, 60 times, 30 times of material/kg/d) it is administered to rat oral gavage, continuous 3 months.As a result the appearance sign of animal, behavioral activity
It is without exception, each group animal feed day's expenditure no significant difference；Body weight increase is normal, each group no significant difference；Hematological examination,
Blood biochemical analysis inspection, main organs histological examination, do not find that obvious toxic reaction occurs.Medicine of the present invention is prompted to big
Mouse administration safe dose is 18g/kg body weight.
Test objective investigates this product and continuously repeats administration to toxic reaction caused by animal and its order of severity, to face
Bed glass bottle for references of safe medication.
Test medicine pharmaceutical composition of the present invention, lot number：20140301.Every 4.47g containing crude drug, dosage daily 3 of being grown up
It is secondary, daily 15.Because of this experiment of dose relationship its dried cream powder administration, every gram contains 11.49 grams of medicinal material.The preceding distilled water of experiment is matched somebody with somebody
It is for experiment into 0.583g powder/ml.
Experimental animal Wistar big white mouse, regular grade, laboratory animal room of Guangxi Medical University provide (SCXK osmanthus 2003-
0003), per 5, cage, standard particle material, 23 ± 2 DEG C of laboratory temperature, relative humidity 70 ± 5% are fed.
Test method chooses healthy white rat 80, body weight 87--110g, and male and female half and half are randomly divided into 4 groups, every group
20.Medication simulates this product clinical administration approach, using gastric infusion.It is respectively clinical daily dose that dosage, which is set,
120 times, 60 times, 30 times of (15.96g/60kg body weight), i.e. 11.66g/kg/ days (134g medicinal materials/kg), 5.83g/kg/ days
(67g medicinal materials/kg), 2.92g/kg/ days (33.5g medicinal materials/kg) three dosage groups and a control group.Control group distills to equivalent
Water.Claim a body weight after medicine weekly, dosage is adjusted by body weight.The general tables such as animal feed, activity, excrement are observed during administration
Existing and toxic reaction situation.Second day after last medicine, 12 rats of every group of execution, blood examination survey hematology and blood biochemical analysis is taken to refer to
Mark.Hematological indices are surveyed with BC1800 types Automatic Blood Cell Analyzer；Determined with the type automatic clinical chemistry analyzer of Roche 7600
Blood biochemical analysis index.And take the main organs of each animal to weigh, calculate per 100g body weight corresponding organs coefficients.Leave and take simultaneously each
The main organs of animal make histopathologic examination.Remaining animal withdrawal observation detects These parameters in 2 weeks in the same way.Respectively give
Medicine group measured value carries out statistical analysis, measurement result overall merit medicine compared with distilled water group, with t values method or correction t values method
The security of thing.
Long term toxicity test time test period is 3 months (convalescence withdrawal observation 2 weeks).
Observation index
1st, general performance：Appearance sign, behavioral activity, glandular secretion, breathing, excrement, feed day's expenditure, body weight, give
Medicine local reaction etc..
2nd, hematological indices：It is red blood cell count(RBC) (RBC), packed cell volume (HCT), mean corpuscular volume (MCV), blood red
Albumen (HB), mean corpuscular hemoglobin (MCHC), mean corpuscular hemoglobin concentration (MCHC) (MCH), reticulocyte count
(RC), platelet count (PLT), white blood cell count(WBC) (WBC) and its classification：Lymphocyte (LYM), monocyte (MID), grain are thin
Born of the same parents (Gran), prothrombin time (PT).
3rd, biochemical index：It is glutamic-pyruvic transaminase (ALT), aspartic transaminase (AST), total serum protein (TP), white
Albumen (ALB), serum total bilirubin (TBIL), urea nitrogen (BUN), creatinine (Cr), T-CHOL (CHOL), alkaline phosphatase
(ALP), glucose (GLU), triglyceride (TG), cretinephosphokinase (CK), Na ion concentration (Na+), chlorine ion concentration
(Cl-), potassium concentration (K+).
4th, histopathologic examination：It is the main organs heart, liver, spleen, lung, kidney, stomach, small intestine, large intestine, adrenal gland, thymus gland, big
Brain, cerebellum, pituitary, spinal cord, oesophagus, tracheae, uterus, ovary, bladder, the naked eyes of marrow and histological examination.And to the heart,
Liver, spleen, lung, kidney, adrenal gland, thymus gland, brain, uterus, ovary are weighed, and calculate its organ coefficient (organ weights/body weight).
Result of the test：
1st, ordinary circumstance：The appearance sign of administration group and control animals, glandular secretion, breathing, excrement, feed daily consumption
Amount, administration local reaction etc. are showed no exception.Feed day's expenditure increases with body weight increase, prolongs with body weight increase and time
It is long and tend towards stability or reduce (the average 15.1 ± 2.1g/ of high dose group only/day, average 14.9 ± 2.0g/ of middle dose group/
Day, low dose group average 15.7 ± 2.8g//day, control group average 16.0 ± 3.5g//day).Administration group body weight increase is just
Often, without significant difference (table 3) compared with control group.
3 months rat body weight growth patterns (X ± SD) of the medicine of the present invention of table 3
Continued 3
Continued 3
2nd, hematological examination：It is administered 3 months and is discontinued 2 weeks, administration group is compared with Normal group, and each index is without conspicuousness
Difference (table 4).
The drug blood measured value (X ± SD) of the present invention of table 4
Continued 4
Continued 4
3rd, blood biochemical analysis inspection：Mid-term, administration 3 months is administered and is discontinued 2 weeks, each detected value administration group and control group it
Between difference without significant difference (table 5).
The medicine rat blood Biochemical value (X ± SD) of the present invention of table 5
Continued 5
Continued 5
4th, organ coefficient inspection：2 weeks after being administered 3 months and being discontinued, the internal organs of administration group rat compared with Normal group
Difference of coefficients is without significant (table 6).
The medicine rat Main Organ Coefficients value of the present invention of table 6 (g/100g body weight, X ± SD)
Continued 6
5th, the histopathologic examination of main organs, the pathological change caused by drug toxicity is had no.
Conclusion：Medicine of the present invention (is respectively equivalent to clinical daily dose with 134g, 67g, 33.5g medicinal material/kg/d respectively
120 times, 60 times, 30 times of 1.117g medicinal materials/kg/d) it is administered to rat oral gavage, continuous 3 months.As a result administration group and control group
The appearance sign of animal, glandular secretion, breathing, excrement, feed day's expenditure, administration local reaction etc. are showed no exception.Feed
Day's expenditure increases with body weight increase, tends towards stability or reduces with body weight increase and the extension of time.Administration group body weight increases
It is long normal, without significant difference compared with control group；Blood routine and blood biochemistry checking, without significant difference compared with control group.It is main
The histopathologic examination of internal organs is wanted, has no the obvious pathological change caused by drug toxicity.Result above prompts medicine of the present invention
The safe dose that rat oral gavage is administered thing is 134g medicinal materials/kg body weight.
Although the embodiment of the present invention/invention is disclosed as above, it is not restricted to specification and embodiment
In listed utilization.It can be applied to various suitable the field of the invention completely., can for those skilled in the art
Easily realize other modification.Therefore under the universal limited without departing substantially from claim and equivalency range, the present invention
It is not limited to specific details and shown here as the legend with description.
Claims (4)
1. a kind of medicine for treating hepatic sclerosis, the described medicine is made up of following weight than component：Golden-rimmed leech 10-60, curcuma zedoary
20-80, giant knotweed 10-50, false-yellowflower milkwort root or herb 4-35, Radix Angelicae Sinensis 4-30, rhizoma alismatis 5-30, Sculellaria barbata 5-40 and Soil unit 5-80.
2. the medicine for the treatment of hepatic sclerosis as claimed in claim 1, wherein the described medicine is made up of following weight ratio ingredient：Gold
Side leech 12-18, curcuma zedoary 26-40, giant knotweed 16-22, false-yellowflower milkwort root or herb 8-25, Radix Angelicae Sinensis 7-16, rhizoma alismatis 10-18, Sculellaria barbata 6-15
With Soil unit 8-16.
3. the medicine for the treatment of hepatic sclerosis as claimed in claim 1, wherein the golden-rimmed leech, curcuma zedoary, giant knotweed, chrysanthemum pour
Lotus, Radix Angelicae Sinensis, rhizoma alismatis, Sculellaria barbata and Soil unit are replaced with extract.
4. the medicine for the treatment of hepatic sclerosis as claimed in claim 1, wherein the formulation of the medicine is：Pill, drops, sustained release
Piece, soft capsule, granule, powder, lozenge, soft extract, syrup, ointment or plastics.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410801986.2A CN104758796B (en) | 2014-12-22 | 2014-12-22 | Treat medicine of hepatic sclerosis and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410801986.2A CN104758796B (en) | 2014-12-22 | 2014-12-22 | Treat medicine of hepatic sclerosis and preparation method thereof |
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| CN104758796A CN104758796A (en) | 2015-07-08 |
| CN104758796B true CN104758796B (en) | 2018-03-09 |
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| CN201410801986.2A Active CN104758796B (en) | 2014-12-22 | 2014-12-22 | Treat medicine of hepatic sclerosis and preparation method thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1429592A (en) * | 2001-12-30 | 2003-07-16 | 李东海 | Liver softening spleen reducing capsule |
| CN101062376A (en) * | 2007-05-23 | 2007-10-31 | 王军 | Oral liquid for softening liver and purging fat |
-
2014
- 2014-12-22 CN CN201410801986.2A patent/CN104758796B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1429592A (en) * | 2001-12-30 | 2003-07-16 | 李东海 | Liver softening spleen reducing capsule |
| CN101062376A (en) * | 2007-05-23 | 2007-10-31 | 王军 | Oral liquid for softening liver and purging fat |
Non-Patent Citations (1)
| Title |
|---|
| 肝硬化的辨证施治;李凌 等;《实用中医内科杂志》;20050405;第19卷(第2期);123-125 * |
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| CN104758796A (en) | 2015-07-08 |
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