CN104095843B - Arctigenin is preparing the application in treating digestive tract ulcer disease medicament - Google Patents
Arctigenin is preparing the application in treating digestive tract ulcer disease medicament Download PDFInfo
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Abstract
The invention belongs to field of medicaments, it is related to the medical usage of arctigenin, and in particular to arctigenin is preparing the purposes in treating digestive tract ulcer disease medicament, is preferably its ejection preparation.Research has shown that：Arctigenin is inhibited to rat water logging stress gastric ulcer, Pylorus Ligated Gastric Ulcer, mouse absolute ethyl alcohol Ulceration, Rat Experimental duodenal ulcer etc., can reduce ulcer index；Dichlorodiphenyl Acetate causes ulcerative colitis in rats to have significant inhibitory action.When arctigenin is used for the treatment of digestive tract ulcer disease, there is the advantages of curative for effect, toxic side effect is low, therefore have broad application prospects.
Description
Technical field
The invention belongs to field of medicaments, it is related to a kind of medical usage of arctigenin, more particularly to arctigenin exists
Prepare the application in treatment digestive tract ulcer disease medicament.
Background technology
Digestive system is made up of oesophagus, stomach and intestine, liver, the organ such as gall-bladder and pancreas, and its major function is that food is carried out
Digestion and absorption, matter and energy source is provided for body metabolism.Because the organ included by it is in peracidity mostly
The relative closure of environment and digestive system, disease of digestive system happen occasionally, and in recent years due to the pressure of environmental pollution
With the raising of people's quality of life, rapid increase trend is presented in the incidence of disease of digestive system.According to statistics, disease of digestive system
Total incidence accounts for population 30%, there is 1/2 disease for being this system in various big hospital outpatient, wherein must emergency treatment be hospitalized for treatment
Person accounts for emergency treatment inpatient 25%；Worldwide, because of the dead number of disease of digestive system, total death toll is accounted for
14%.Wherein digestive tract ulcer disease is one of digestive system common disease frequently-occurring disease, and it refers mainly to occur gastral slow
The disease of property ulcer or ulcer sample pathological characteristic.Clinically common digestive tract ulcer disease is mainly peptic ulcer and burst
Ulcer colitis.
Peptic ulcer (peptic ulcer, PU) is to refer mainly to occur in stomach and duodenal chronic ulcer, i.e. stomach
Ulcer and duodenal ulcer, can also betide lower esophagus, gastroduodenal previous anastomotic nearby and Meckel diverticulums.Doctor trained in Western medicine
Limitation tissue defect is summarized as, the disease of mucous membrane, submucosa and muscle layer can be involved, the traditional Chinese medical science will according to its clinical symptoms
It belongs to the category of " epigastric pain ".The course of disease is longer, recurrent exerbation, complicated clinical manifestation, is a kind of global common
Chronic gastrointestinal disorders.Available data shows that peptic ulcer accounts for the 10.3%~2.6% of domestic gastrocopy crowd.The disease is found in
Any age, in the majority with 20~50 years old, male is more than women（2~5: 1）, clinically duodenal ulcer be more than gastric ulcer, two
The ratio between person is about 3: 1.Peptic ulcer mechanism is sufficiently complex, it is generally recognized that peptic ulcer is due to stomach lining
Damage factor and defending factors between it is unbalance caused by.When the damage factor to stomach lining is more than defending factors, digestion
Property ulcer may be formed, in addition, mental element, inherent cause and some other factor have also assisted in PUD generation
Complicated mechanism of causing a disease.
Ulcerative colitis (ulcerative colitis, UC) also known as chronic nonspecific ulcerative colitis, be with
Directly, the shallow property of the table of colon, based on nonspecific inflammation disease, with the disease of parenteral multiple organ injury, it is now recognized that this disease is with losing
Biography factor is relevant, is basic using autoimmune mechanism, infection, neural factors are inducement, and lesion is mainly in rectum, sigmoid colon.
It is the diffusivity inflammation change of mucous membrane shallow-layer first.Followed by hyperemia, oedema, plumpness and fragility increase, produce aphtha, Jin Erfa
Big ulcer is transformed into, late period, intestinal wall was thickening, narrow, intestinal tube shortens due to colon's hyperplasia.Its course of disease is very long, has a strong impact on trouble
The health and quality of life of person, and the probability increase of the extension generation colorectal cancer with the course of disease, therefore by the World Health Organization
It is classified as one of modern difficult treatment.This disease is more American-European rare in China, and the course of disease is general relatively light, but illness rate increases increasingly in recent years,
Severe also it is commonly reported that.
Medicine at present clinically for digestive tract ulcer disease is more, antiacid, proton pump inhibitor, H2- acceptors
Antagonist and gastric mucosa protective agent are the key agents of current domestic anti-peptic ulcer, but these medicines are usually present not
With the adverse reaction of degree, and recurrence rate after healing is high, and satisfied therapeutic effect can not be obtained to peptic ulcer.It is right both at home and abroad
The scheme for the treatment of of ulcerative colitis is basically identical, main to include applying traditional chemical agents, aminosalicylic acids, hormone and exempts from
Epidemic disease inhibitor, and the biology preparation of new development.But treatment of the medicine to ulcerative colitis is only capable of making disease amelioration, and
Can not thoroughly it cure.Therefore, people pay much attention to the curative of research and development treatment digestive tract ulcer disease for a long time
Thing, for mitigating patient suffering, the quality of life tool for improving patient is of great significance for it.
Great burdock achene is the dry mature fruit of composite family biennial herb plant burdock, also known as Great Burdock Achene, FRUCTUS ARCTII, evil are in fact
Deng.Great burdock achene belongs to conventional Chinese medicine, and the traditional Chinese medical science thinks that it has dispelling wind and heat from the body, facilitaing lung promoting eruption, relieving sore-throat dissipating bind, the work(of removing toxicity for detumescence
Effect, for anemopyretic cold, coughing with a lot of sputum, measles, rubella, abscess of throat, mumps erysipelas, carbuncle sore tumefacting virus.Doctor trained in Western medicine think it except
Outside with pharmacological actions such as diuresis, disperse accumulations, eliminating the phlegm stopping leaks, constipation, the dietotherapy of hypertension, high-cholesterol disease are additionally operable to.Burdock master
To contain lignin compound, based on arctiin and arctigenin.According to experimental studies have found that, arctigenin compares ox
Burdock glycosides has stronger physiologically active, and arctiin is broken down into arctigenin in vivo and produces numerous pharmacological actions.At present,
Existing document report arctigenin has following pharmacological activity：1）Anti-inflammatory and immunoregulation effect；2）Antivirus action, including
HIV-1 and influenza virus；3）The effect of inducing apoptosis of tumour cell；4）Nephrosis and diabetes, treating diabetic complications effect；
5）Heat shock response inhibitory action；6）Neuroprotection；7）Expand blood vessel function；8）Platelet activating factor antagonism；
9）The effect of Anti-alzheimer's disease；10）Suppress effect of K+ contractures etc..Such as Cho J Y, et
Al.Immunomodulatory effect of arctigenin, a lignan compound on tumor necrosis
Factor- α and nitric oxide production, and lymphocyte proliferation [J] .Pharm
Pharmcol.1999;51(11):1267-1273. disclosing arctigenin has anti-inflammatory and immunoregulation effect；Gao Y,
et al.Activity of in vitro anti-influenza virus of arctigenin[J].Chinese
Traditional and Herbal Drugs (Chinese herbal medicine) .2002;33(8):724-726. disclosing arctigenin has
Antiviral effect；Kim S H, et al.Hepatoprotective dibenzylbutyrolactone lignans of
Torreya nucifera against CCl4-induced toxicity in primary cultured rat
hepatocytes[J].Biol Pharm Bull.2003;26(8):1202-1205. disclosing arctigenin has induction
The effect of apoptosis of tumor cells.
Arctigenin has the function that significant antibacterial, antiviral, antitumor, anti-paf receptor, but prior art is not
There is the report of arctigenin treatment digestive tract ulcer disease.Based on this, spy proposes the present invention.
The content of the invention
The defects of in order to overcome prior art, the present invention provide a kind of medicine for treating digestive tract ulcer disease.This is controlled
Medicine is treated using arctigenin as active constituents of medicine, when it is used for the treatment of digestive tract ulcer Disease, has curative effect true
Cut, the characteristics of toxic side effect is low, and the security of arctigenin and tolerance are preferable, have quite varied medical applications
Prospect.
Arctigenin involved in the present invention is that the effective therapeutic component obtained is extracted from great burdock achene, on evidence
Prove that arctigenin has extensive pharmacological activity, the present inventor has found that arctigenin can by substantial amounts of experimental study
To significantly inhibit the development or generation that betide gastral ulcer disease extensively, so as to propose that arctigenin is controlled in preparation
The application in digestive tract ulcer disease medicament is treated, therefore the present invention relates to a kind of new medical usage of arctigenin, i.e.,
Arctigenin is used to prepare the application in treatment digestive tract ulcer disease medicament.
In the such use of arctigenin disclosed by the invention, arctigenin can significantly inhibit digestive tract ulcer
Disease, when it is used for the treatment of digestive tract ulcer disease, the people of arctigenin with dosage be 0.01mg/kgd~
50mg/kgd, preferably 0.1mg/kgd~10mg/kgd.For controlling for other mammalian digestive tract ulcer diseases
During treatment, it can be converted and formed according to the clinical dosage of people and animal, this is easily able to those skilled in the art.
Arctigenin can be prepared into the treatment that suitable pharmaceutical preparation is used for digestive tract ulcer disease in the present invention
Or prevention, as arctigenin can develop into the use that oral formulations, sublingual administration preparation or ejection preparation facilitate patient, its
Described in oral formulations can be tablet, capsule or microemulsion formulation, preferably tablet；The sublingual administration preparation is to contain ox
Burdock aglycon and the pharmaceutical preparation for being applicable sublingual administration, it is preferably its sublingual lozenge；The ejection preparation can be its parenteral solution,
Inject micro emulsion etc., preferably parenteral solution.When arctigenin is prepared into parenteral solution, pharmaceutically acceptable carrier can be injection
With water, sodium chloride, sodium citrate, citric acid, glycerine, ethanol, propane diols etc..Arctigenin parenteral solution described above can be with
Suitable additives are added according to the property of medicine, as osmotic pressure regulator, pH adjusting agent, solubilizer, antioxidant, bacteriostatic agent,
Emulsifying agent, suspending agent etc., wherein the solubilizer is polyethylene glycol 400, any one or two kinds in Tween-80.Above-mentioned ox
In burdock aglycon parenteral solution, content containing effective ingredient arctigenin in each preparation unit for 0.01mg~
50mg, preferably 0.01mg-10mg.
When arctigenin is used to treat or prevent digestive tract ulcer disease, achieve has compared with prior art as follows
The technique effect of benefit：
1st, arctigenin of the present invention has significant therapeutic effect to alimentary canal ulcer disease.The present invention's
Arctigenin answers rat water logging acute gastric ulcer, Pylorus Ligated Gastric Ulcer, mouse absolute ethyl alcohol Ulceration, rat real
The property tested duodenal ulcer etc. has significant inhibitory action, can reduce ulcer index；Dichlorodiphenyl Acetate causes rat ulcer colon
Inflammation has significant inhibitory action.
2nd, arctigenin of the present invention is the natural traditional Chinese medicine monomer for extracting to obtain in traditional Chinese medicine great burdock achene, and its is right
Human body toxic side effect is low, can significantly improve the drug safety and compliance of patient, and then significantly improves digestion
The therapeutic effect and quality of life of road ulcer disease patient.
Embodiment
The content of the invention of the present invention is further illustrated below by way of specific embodiment, it is to be understood that the embodiment of the present invention
It does not limit the invention in any way.
The arctigenin parenteral solution of embodiment 1
Preparation technology：The propane diols of recipe quantity and ethanol are well mixed, arctigenin is added, stirring and dissolving, adds
0.9% sodium chloride solution of recipe quantity, stirs, and adds 0.5% needle-use activated carbon, stirring, takes off charcoal, produce.
The arctigenin parenteral solution of embodiment 2
Preparation technology：The PEG-400 of recipe quantity and ethanol are well mixed, arctigenin is added, stirring and dissolving, adds
0.9% sodium chloride solution of recipe quantity stirs to 10L, adds 0.5% needle-use activated carbon, stirring, take off charcoal, produce.
The arctigenin parenteral solution of embodiment 3
Preparation technology：The ethanol of recipe quantity and Tween-80 are well mixed, arctigenin is added, stirring and dissolving, adds
Water for injection stirs to 10L, adds 0.5% needle-use activated carbon, stirring, take off charcoal, produce.
The arctigenin parenteral solution of embodiment 4
Arctigenin 0.01g
Ethanol 3.3L
Water for injection adds to 10L
Preparation technology：The ethanol of recipe quantity is added into arctigenin, stirring and dissolving, adds water for injection to 10L, stirring
Uniformly, 0.5% needle-use activated carbon is added, stirring, charcoal is taken off, produces.
The preparation of the tablet of embodiment 5
Preparation technology：Arctigenin and microcrystalline cellulose excipients, sodium carboxymethyl starch are well mixed, added appropriate
8% starch slurry softwood, then cross the granulation of 16 mesh sieves.For wet granular in 60 DEG C of dryings, dry particl crosses 20 mesh sieve whole grains, sifts out dry granular
In fine powder, mix, then mixed again with dry particl, tabletting with magnesium stearate, per agreement that contracts a film or TV play to an actor or actress 200mg, produced.
The arctigenin sublingual lozenge of embodiment 6
| Sub- aglycon by ox | 10g |
| Lactose | 30g |
| Microcrystalline cellulose | 30g |
| Sucralose | 2g |
| PVPP | 3g |
| NaTDC | 5g |
| Superfine silica gel powder | 1g |
| Magnesium stearate | 1g |
Preparation technology：Said components drying, pulverize and sieve pretreatment after mix direct tablet compressing be made.
The arctigenin sublingual lozenge of embodiment 7
| Sub- aglycon by ox | 5g |
| Sugar | 40g |
| Lactose | 20g |
| Sodium carboxymethylcellulose | 2g |
| Hydroxyethyl cellulose | 3g |
| NaTDC | 2g |
| Magnesium stearate | 1g |
Preparation technology：By main ingredient and the drying of each adjunct ingredient, pretreatment is pulverized and sieved, by main ingredient and sugar, lactose, carboxylic first
Base sodium cellulosate is mixed, and prepared by the material of mixing into softwood using pure water as adhesive, is crossed the granulation of 20 mesh sieves and is done at 60 DEG C
Dry preparation dry particl, magnesium stearate is added to above-mentioned dry particl and always mixed, tabletting produces.
The micro emulsion concentrate of embodiment 8
Preparation technology：Weigh recipe quantity medium-chain fatty glyceride, Polyoxyethylene castor oil EL-40,1,2-PD, nothing
Water-ethanol, stirred after mixing, then add arctigenin dissolving, can also ultrasonication to accelerate to dissolve, obtain clear
Clear concentrate, as arctigenin micro emulsion concentrate.Above-mentioned micro emulsion concentrate can be further diluted for injection or oral.
The micro emulsion concentrate of embodiment 9
Preparation technology：Stirred after weighing recipe quantity PEG-2- stearates, Tween-20,1- hexanols, PEG3350 mixing
It is even, then add arctigenin dissolving, can also ultrasonication to accelerate to dissolve, obtain clarification concentrate, as great burdock achene
Aglycon micro emulsion concentrate.Above-mentioned micro emulsion concentrate can need further be diluted according to medication for patient's drug administration by injection or
It is administered orally.
Inhibitory action of the arctigenin of embodiment 10 to rat Pylorus Ligated Gastric Ulcer
1st, experiment packet and modeling：
SD rats 50 are taken, body weight is 180~220g, male and female half and half, is randomly divided into 5 groups, model control group is subcutaneously injected
Isometric carboxymethyl cellulose；Arctigenin Gao ﹑ low dose groups press 10mg/kg respectively, and great burdock achene is subcutaneously injected in 0.1mg/kg
Aglycon parenteral solution（It is made according to the formulation and technology of the embodiment of the present invention 1）；Burdock extract group（Using Ana C.dos Santos
《Gastroprotective activity of the chloroform extract of the roots from
Arctium lappa L.》Preparation technology obtain Radix Arctii chloroform extract）The extraction of 10mg/kg great burdock achenes is subcutaneously injected
Thing；10mg/kg Omeprazoles are subcutaneously injected in Omeprazole group.7d is administered in continuous subcutaneous injection.Fasting 48h before experiment, before experiment
1h last time subcutaneous administrations.It is anesthetized with ether, in belly median incision, ligatures pylorus, suture.
2nd, method and data processing：
The calculating of 2.1 ulcer areas：After rat pylorus ligation modeling 19h, sacrificed by exsanguination is simultaneously cut open the belly, and ligation orifice of the stomach takes stomach
Go out, after collecting gastric juice, inject 1% formalin 10ml from orifice of the stomach, be then dipped in 1% formalin and fix more than 5min, along stomach
The big curved stomach that cuts open observes ulcer area, and calculation formula is S=π × (d1/2)×(d2/ 2), S is ulcer area, and π is pi, d1For
The maximum measured by ulcer center indulges footpath, d2For the maximum transverse diameter measured by ulcer center.
The measure of 2.2 gastric juice amounts, gastric acidity and peptic activity of stomach：The gastric juice of collection is moved in centrifuge tube, centrifuged
Gastric content is precipitated, is placed in pipette, extract 1ml gastric juice supernatant in conical flask, phenolphthalein is added and methyl red indicator is each
Two drops, it is yellow by red change that liquid is titrated to 0.01mol/LNaOH solution, records the NaOH volumes (v of consumption1), continue to be titrated to
Liquid color is red by xanthochromia, records the NaOH volumes (v of consumption2), gastric acidity is calculated, formula is:Acidity=100N/v, N are drop
Fixed NaOH used amount (mmol)；Gastric juice amount used when v is titrates.
Effect of the arctigenin of table 1 to rat Pylorus Ligated Gastric Ulcer
Note：Compared with model control group,#P ＜ 0.05；##P ＜ 0.01；
Compared with burdock extract group,&P ＜ 0.05；&&P ＜ 0.01；
Compared with Omeprazole group,@P ＜ 0.05.
Experimental result is shown in Table 1, and experimental result is shown：
(1) after being administered, the formation of rat gastric ulcer caused by each treatment group can significantly inhibit pylorus ligation, ulcer surface is reduced
Product (P<0.05), and gastric juice amount, gastric acidity (P can be reduced<0.05), show Omeprazole group, burdock extract group and
Arctigenin high and low dose group is respectively provided with certain therapeutic action to Pylorus Ligated Gastric Ulcer.
(2) compared with burdock extract group, arctigenin high and low dose group ulcer area is obviously reduced, burdock
Sub- each dosage group of aglycon compared with burdock extract group, has conspicuousness or pole conspicuousness poor in terms of ulcer area is reduced
It is different.
(3) compared with Omeprazole group, arctigenin high dose group ulcer area is obviously reduced, and has significant difference
(P<0.05), show that therapeutic action of the arctigenin to Pylorus Ligated Gastric Ulcer becomes apparent from compared with Omeprazole.
Inhibitory action of the arctigenin of embodiment 11 to rat water logging stress gastric ulcer
1st, method：
The duplication of 1.1 Ulcer Models and the index of ulcer level：SD rats 60 are taken, body weight is 200~250g, male,
It is randomly divided into 6 groups.Fasting 24h before experiment, free water.Experimental group 30min before water-immersion stress, high and low dose of arctigenin
Amount group difference gavage arctigenin 50mg/kg, 10mg/kg；Burdock extract group（Preparation method is the same as above-described embodiment 8）Fill
Stomach 30mg/kg burdock extracts；Omeprazole group gavage 30mg/kg Omeprazoles.With 5g/L carboxylic first before above medicine use
Base cellulose solution is made into required concentration.The carboxymethyl cellulose of blank control group, model control group gavage respective volume.Water temperature
（23±1）DEG C, water-immersion stress 5h, animal is put to death, observe ulcer situation.Ulcer index, petechial hemorrhage are calculated by Cuth method
For 1 point；Streak-like hemorrhage, length<1mm is 2 points, and 1~2mm is 3 points, and 2~4mm is 4 points,>4mm is 5 points, width>Score value during 1mm
×2。
1.2 data processing：Data are with mean ± standard deviationRepresent.According to every group of ulcer index of gained, by ulcer
The calculation formula of inhibiting rate：Ulcer inhibition rate=[(control class index-administration class index)/control class index] × 100%；Calculate routed
Ulcer inhibiting rate.The comparison of each group difference is examined using t.
2. result：
Effect of the arctigenin of table 2 to rat water logging stress gastric ulcer
Note：Compared with model control group,##P ＜ 0.01；Compared with burdock extract group,&P ＜ 0.05；&&P ＜ 0.01；
Compared with Omeprazole group,@P ＜ 0.05.
As seen from the results in Table 2, (1) each treatment group has significant difference (P compared with model control group<0.01), show
Omeprazole group, burdock extract group and great burdock achene high and low dose group can significantly reduce ulcer index, to rat water logging
Stress gastric ulcer has significant therapeutic effect.
(2) compared with burdock extract group, arctigenin high and low dose group ulcer index is obviously reduced, burdock
Sub- each dosage group of aglycon compared with burdock extract group, has conspicuousness or pole conspicuousness poor in terms of ulcer index is reduced
It is different.
(3) compared with Omeprazole group, arctigenin high dose group ulcer index is obviously reduced, and has significant difference
(P<0.05), show that therapeutic action of the arctigenin to water logging stress gastric ulcer becomes apparent from compared with Omeprazole.
Inhibitory action of the arctigenin of embodiment 12 to mouse absolute ethyl alcohol Ulceration
1st, method：
The duplication of 1.1 Ulcer Models and the index of ulcer level：60 male ICR mouses are randomly divided into 6 groups, every group 10
Only:Isometric carboxymethyl cellulose is subcutaneously injected in Normal group and absolute ethyl alcohol model group；Arctigenin high and low dose is given
Medicine group presses 2.0mg/kg respectively, and arctigenin is subcutaneously injected in 0.5mg/kg；Burdock extract group（Preparation method is the same as above-mentioned reality
Apply example 8）10mg/kg burdock extracts are subcutaneously injected；10mg/kg Omeprazoles are subcutaneously injected in Omeprazole group.Continuous 5d, in
1h after last dose, in addition to normal group, remaining equal gavage absolute ethyl alcohol 0.1ml/20g.Cervical vertebra is all taken off after 1h to put to death, and is cut open the belly,
Ligation orifice of the stomach, pylorus take out stomach behind end respectively, and 10% formaldehyde 6ml is injected into stomach, full stomach are placed in formalin fixed
15min, cut off along greater curvature, normal saline flushing, with filter paper suck dry moisture.Utilize slide measure measure gland area strip damage
Length be more than 1mm person, measure length, every millimeter is remembered 1 point, and its width, which is more than 1mm person's score, to be doubled, and length is respectively less than with width
1mm, 0.5 point is counted, score is added as to the ulcer index of the animal, calculate ulcer inhibition rate, ulcer inhibition rate (%)=(model
Group ulcer index-administration group ulcer index)/model group ulcer index × 100%.
1.2 data processing：Data are with mean ± standard deviationRepresent.The comparison of each group difference is examined using t.
2. result：
The arctigenin of table 3 causes the effect of mouse gastric ulcer to absolute ethyl alcohol
Compared with model control group,#P ＜ 0.05,##P ＜ 0.01；Compared with burdock extract group,&P ＜ 0.05；&&P ＜
0.01；
Compared with Omeprazole group,@P ＜ 0.05.
(1) in terms of stomach sample, normal group mucosa surface is smooth；Streak or petechial hemorrhage is presented in model group ulcer more；
Compared with model group, the stomach lining petechial hemorrhage and degree of injury of administration group have different degrees of mitigation.As a result show, Aomei is drawn
Mucosal lesion caused by azoles group, burdock extract group and the obvious Anti-ethanol of arctigenin high and low dose group energy, with mould
Type group, which compares ulcer index, substantially reduces (P<0.05), there is certain protective effect to stomach lining.
(2) compared with burdock extract group, arctigenin high and low dose group ulcer index is obviously reduced, burdock
Sub- each dosage group of aglycon compared with burdock extract group, has conspicuousness or pole conspicuousness poor in terms of ulcer index is reduced
It is different.
(3) compared with Omeprazole group, arctigenin high dose group ulcer index is obviously reduced, and has significant difference
(P<0.05), show that therapeutic action of the arctigenin to absolute ethyl alcohol Ulceration becomes apparent from compared with Omeprazole.
Inhibitory action of the arctigenin of embodiment 13 to Rat Experimental duodenal ulcer
1st, method：
The duplication of 1.1 Ulcer Models and the index of ulcer level：
Healthy male Wistar big white mouse 60,200 ± 30g of body weight.Water 24h is can't help in fasting before experiment, after mark of weighing
It is randomly divided into 6 groups, every group 10:Isometric carboxymethyl cellulose is subcutaneously injected in Normal group and model group；Arctigenin
Arctigenin is subcutaneously injected by 1.0,2.0mg/kg respectively in Gao ﹑ low dosages administration group；Burdock extract group（Preparation method is same
Above-described embodiment 8）10mg/kg burdock extracts are subcutaneously injected；10mg/kg Omeprazoles are subcutaneously injected in Omeprazole group.Ten
Two Duodenalulcer models make with reference to Szabo methods.10% cysteamine, dosage 280mg/kg are subcutaneously injected respectively after administration 1h.
Side arteria carotis communis is separated after 24h under etherization, takes blood about 3ml blood supplies Gastrin to detect.Then cervical approach is taken off to put to death greatly
Mouse, cut open the belly, ligature pyloric ring and orifice of the stomach, take out stomach and duodenum, collect after gastric juice along greater curvature and mesoduodenum pair
Sample is cut off in side, observes duodenal ulcer formational situation, and measure ulcer size.
1.2 data processing：Data are with mean ± standard deviationRepresent.The comparison of each group difference is examined using t.
2. result：
Effect of the arctigenin of table 4 to Rat Experimental duodenal ulcer
Note：Compared with model control group,#P ＜ 0.05,##P ＜ 0.01；
Compared with burdock extract group,&P ＜ 0.05；&&P ＜ 0.01；
Compared with Omeprazole group,@P ＜ 0.05.
Test result indicates that：(1) each treatment group can mitigate the degree of injury of duodenal mucosa and body of gland, reduce ulcer
Area.
(2) compared with burdock extract group, arctigenin high and low dose group ulcer index is obviously reduced, burdock
Sub- each dosage group of aglycon compared with burdock extract group, has conspicuousness or pole conspicuousness poor in terms of ulcer index is reduced
It is different, and as the increase of dosage, its preventive effect are also more obvious.
(3) compared with Omeprazole group, arctigenin high dose group ulcer index is obviously reduced, and has significant difference
(P<0.05), show that therapeutic action of the arctigenin to Rat Experimental duodenal ulcer becomes apparent from compared with Omeprazole.
The arctigenin Dichlorodiphenyl Acetate of embodiment 14 causes the inhibitory action of ulcerative colitis in rats
1st, method：
The duplication of 1.1 models and the index of ulcer level：Healthy SD rat 60 is taken, body weight (200 ± 20) g is male, with
Machine is divided into Normal group, model control group, burdock extract group（Preparation method is the same as above-described embodiment 8）It is subcutaneously injected
10mg/kg is subcutaneously injected in 10mg/kg burdock extracts, arctigenin 0.01mg/kg, 0.25mg/kg group, Omeprazole group
Omeprazole；Normal group and model control group, which are subcutaneously injected, gives isometric 0.5%CMC, once a day, modeling after 2d.
Ulcerative colitis modeling method is:Rat Fast can't help water 48h, will be led after yellow Jackets 30mg/kg intraperitoneal injection of anesthesia
Urinary catheter per anum inserts 8cm, and (Normal group replaces acetic acid molten to injection 1mL10% acetic acid normal saline solution with physiological saline
Liquid), anus reinjects 2mL normal saline flushings 1 time after hand rest 20s upward down on head.Continue that 6d is administered, prohibit after last dose
12h is eaten, the neck that breaks is put to death, and cuts open the belly take out anus to whole colon and the rectum section of cap end rapidly, intestines are cut off along mesenterium edge
Chamber, intestinal contents is rinsed well with physiological saline, filter paper is wiped dry, and then whole intestinal segment is laid on aluminium sheet, visually observed
Scoring, standards of grading are shown in Table 5.Leave and take each group rat colon lesion and most substantially locate one piece of tissue, correct amount, various concentrations are made
Tissue homogenate, MDA (MDA) and myeloperoxidase (MPO) content is determined by kit method.
The huge inspection standards of grading of the Traumatic Colon of table 5
1.2 data processing：Data are with mean ± standard deviationRepresent, counted using SPSS10.0for windows
Software, compare using One-Way ANOVA, P between the equal array of each group<0.05 difference is statistically significant.
2. result：
The arctigenin Dichlorodiphenyl Acetate of table 6 causes the influence of ulcerative colitis in rats
Compared with model control group,*P ＜ 0.05,**P ＜ 0.01；Compared with burdock extract group,&P ＜ 0.05；&&P ＜
0.01；
Compared with Omeprazole group,@P ＜ 0.05.
(1) the huge inspection of acetic acid modeling postcolon shows the adhesion of colon intestinal wall, thickened, inner surface ulcer.Each treatment group and model
Control group is compared, and has significant difference (p<0.05).Show burdock extract group and arctigenin high and low dose group pair
Ulcerative colitis has significant therapeutic effect caused by acetic acid.
(2) compared with burdock extract group, the huge inspection scoring of arctigenin high and low dose group is obviously reduced, great burdock achene
Each dosage group of aglycon compared with burdock extract group, has conspicuousness or pole conspicuousness poor in terms of ulcerative colitis is suppressed
It is different.
(3) compared with Omeprazole group, the huge inspection scoring of arctigenin high dose group is obviously reduced, and has significant difference
(P<0.05), show that therapeutic action of the arctigenin to ulcerative colitis becomes apparent from compared with Omeprazole.
Local mucous membrane of colon MDA and MPO is significantly raised after acetic acid modeling, each dosage group MDA of arctigenin and MPO contents
(P is significantly reduced compared with model control group<0.05).MDA is a kind of lipid peroxidation product, and reflection body cell is by oxygen radical
The order of severity of attack.Test result indicates that arctigenin can mitigate Injured colonic mucosa caused by oxygen radical, the effect
May be relevant with diseased region arctigenin antioxidation.MPO is that content is higher in neutrophil leucocyte azurophilic granule
Peroxide enzyme, the macrophage in tissue are free of MPO, if MPO activity increases in tissue, reflect that neutral grain is thin in tissue
Born of the same parents increase, and have inflammation.Organize MPO activity to reduce in experiment and show that arctigenin can mitigate diseased region degree of inflammation.
Claims (8)
1. purposes of the arctigenin in treatment gastric ulcer or duodenal ulcer disease medicine is prepared.
2. purposes as claimed in claim 1, it is characterised in that people's dosage of arctigenin be 0.01 mg/kgd ~
50mg/kg·d。
3. purposes as claimed in claim 2, it is characterised in that people's dosage of arctigenin be 0.1 mg/kgd ~
10mg/kg·d。
4. purposes as claimed in claim 1, it is characterised in that arctigenin is oral formulations, sublingual administration preparation or injection
Preparation.
5. purposes as claimed in claim 4, it is characterised in that the arctigenin oral formulations are tablet, capsule or mouth
Take microemulsion formulation；The sublingual administration preparation is sublingual lozenge；The arctigenin ejection preparation is that parenteral solution or injection are micro-
Emulsion formulation.
6. purposes as claimed in claim 5, it is characterised in that the arctigenin parenteral solution contains arctigenin, medicinal
Carrier and water for injection, wherein the pharmaceutical carrier is sodium chloride, sodium citrate, citric acid, appoint in glycerine, ethanol, propane diols
Meaning is a kind of or it is combined.
7. purposes as claimed in claim 6, it is characterised in that the arctigenin parenteral solution also includes solubilizer, the increasing
Solvent is any one or two kinds in polyethylene glycol 400, Tween-80.
8. purposes as claimed in claim 5, it is characterised in that the content of arctigenin is in arctigenin ejection preparation
0.01mg~50mg。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310123506.7A CN104095843B (en) | 2013-04-10 | 2013-04-10 | Arctigenin is preparing the application in treating digestive tract ulcer disease medicament |
| HK14111659.3A HK1198128A1 (en) | 2013-04-10 | 2014-11-19 | Use of arctigenin in the preparation of medicament for the treatment of gastrointestinal ulcer diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310123506.7A CN104095843B (en) | 2013-04-10 | 2013-04-10 | Arctigenin is preparing the application in treating digestive tract ulcer disease medicament |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104095843A CN104095843A (en) | 2014-10-15 |
| CN104095843B true CN104095843B (en) | 2018-03-20 |
Family
ID=51664640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310123506.7A Active CN104095843B (en) | 2013-04-10 | 2013-04-10 | Arctigenin is preparing the application in treating digestive tract ulcer disease medicament |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN104095843B (en) |
| HK (1) | HK1198128A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105982887A (en) * | 2015-02-09 | 2016-10-05 | 山东新时代药业有限公司 | Application of arctigenin in preparing medicine for treating blood hyperviscosity |
| CN108721274B (en) * | 2017-04-24 | 2023-07-25 | 鲁南制药集团股份有限公司 | Application of arctigenin in preparation of medicine for treating chronic atrophic gastritis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1973684A (en) * | 2006-12-28 | 2007-06-06 | 李仕贵 | Delicious Chinese dumpling with burdock and meat in the stuffing |
-
2013
- 2013-04-10 CN CN201310123506.7A patent/CN104095843B/en active Active
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2014
- 2014-11-19 HK HK14111659.3A patent/HK1198128A1/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1973684A (en) * | 2006-12-28 | 2007-06-06 | 李仕贵 | Delicious Chinese dumpling with burdock and meat in the stuffing |
Non-Patent Citations (3)
| Title |
|---|
| "核因子-κB的表达在溃疡性结肠炎发病机制中的意义";刘一品，李延青;《胃肠病学》;20061231;第11卷(第2期);103-106 * |
| "消化性溃疡患者幽门螺杆菌感染与IL-8、IL-10、TNF-α的关系";郭志强;《中国实用医药》;20130131;第8卷(第3 期);70-71 * |
| "牛蒡中活性物质的提取、分离纯化及其生理功能的研究进展";贺菊萍;《食品工业科技》;20121231;第33卷(第10期);407-411 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104095843A (en) | 2014-10-15 |
| HK1198128A1 (en) | 2015-03-13 |
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