CN103977076B - Fructus schizandrae total lignans are being prepared for treating the application in the medicine coughed - Google Patents
Fructus schizandrae total lignans are being prepared for treating the application in the medicine coughed Download PDFInfo
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Abstract
The new application in treating the medicine or health products of cough is being prepared the present invention relates to fructus schizandrae total lignans, specifically the new application such as in preparing treatment antibechic, alleviation cough and eliminating the medicine or health products of airway inflammation.Experiment shows that fructus schizandrae total lignans can substantially reduce smoke from cigarette and stimulate the cough number of times for causing Cough reflex sensitivity to increase cavy and citric acid smoke stimulation cause acute cough cavy, extend cough latent period, and can significantly mitigate the airway inflammation that smoke from cigarette stimulates cause Cough reflex sensitivity to increase cavy, point out fructus schizandrae total lignans to can be used for preparing antibechic, alleviate the medicine coughed and eliminate airway inflammation.
Description
Technical field
The invention belongs to biomedicine field, it is related to fructus schizandrae total lignans and is preparing the use for the medicine for being used to treat cough
On the way, particularly fructus schizandrae total lignans are in the new application for preparing antibechic, alleviating in coughing and eliminating the medicine of airway inflammation.
Background technology
Cough is the most common symptom of internal clinic, sees various respiratory system and non-respiratory systemic disease.Cough is in itself
It is a kind of defense mechanism, removes in air flue excessive secretion and prevent foreign matter suction air flue by mistake.But cough for a long time
But the quality of life of patient has been had a strong impact on and has caused the serious psychological burden of patient, while also significantly increasing personal and public
Expenditures for medical care and public health.
Divide according to the course of disease, cough include acute cough (<3 weeks), subacute cough (3~8 weeks) and chronic cough (>=8
Week).The treatment coughed at present is typically all to be treated using central antitussive, peripheral antitussive and expectorant etc., and one
As can receive preferable curative effect.Even if but still having part acute and chronic cough using the central antitussive thing such as codeine, cough
It can not still be eased, so that many acute coughs develop into chronic cough, some Chronic Cough Patients courses of disease even reach
To decades.
Many parts of Foreign Epidemic diseases learn research and show the incidence of disease about 9%~33% of the chronic cough in general population, 2003
One Britain's epidemiology survey shows, chronic cough is in a middle-aged person's incidence of disease of 50~59 years old up to 12%, Chronic Cough Patients
Account for breathing the 20% of special outpatient clinic patient.In recent years with the gradually exacerbation (such as PM2.5, PM10) of air environmental pollution, slowly
Property cough illness rate be also possible to continue rise.Current research thinks to cause the Etiological of chronic cough to include：Cough becomes
Different in nature asthma, Eosinophilic bronchitis, gastroesophageal reflux induced cough, epithelium healing cough syndrome.For the above-mentioned cause of disease
Caused cough, it then follows cough guide is treated accordingly, most of patient's cough can be relieved.However, still having
Part Chronic Cough Patients are shown no obvious abnormalities after serial comprehensively inspection, but cough symptom is persistently present, and is previously referred to as
For chronic idiopathic cough (Chronic idiopathic cough, CIC), its cough symptom treats not good, and without specific aim
Etiological treatment, is difficult point and the emphasis place in current chronic cough field.Studies have found that chronic idiopathic cough is with a middle-aged person
It is common, more to catch a cold for triggering factors, long-term existence of hereafter coughing, generally to oil smoke, penetrating odor, cold air, cigarette cigarette
The quite sensitives such as mist, even laugh or speech can induce cough, show as Cough reflex sensitivity and substantially increase sometimes.For such a feelings
Condition, high quick syndrome (the Cough hypersensitivity of cough are referred to as by the chronic cough that Cough reflex sensitivity increases
Syndrome, CHS).It is key feature that the high quick syndrome patient of chronic cough has that Cough reflex sensitivity increases extremely.
It is temporarily available without suitable treatment means at present for the patient for high quick syndrome of coughing, mostly by antitussive
Thing maintaining treatment.But antitussive medicine, such as codeine and dextromethorphan, the side effect of various degrees, such as constipation, town
Quiet, respiration inhibition etc., thus limit it and use, and part cough high quick syndrome patient even with central antibechic
Medicine, cough can not also be alleviated, and have a strong impact on daily life quality.
The fruit of Chinese magnoliavine is sour, sweet, warm-natured.Return lung, the heart, kidney channel.Lung being a delicate viscus, evil is dry, and the sweet Wen Errun of the fruit of Chinese magnoliavine, moistening lung stops
Cough；Chronic cough causes the failure of the kidney in receiving air, and the sour convergence of the fruit of Chinese magnoliavine helps kidney to receive gas, and chronic cough caused by treating lung yin virtual loss, the failure of the kidney in receiving air is work(
Effect is very big.《Book on Chinese herbal medicine can be compiled》Record：" overstrain cough preferably uses northern person；Chill preferably uses southern person in lung "；《Medicineization justice》Record：" the five tastes
Son ... can restrain lung qi, cure mainly consumptive disease chronic cough "；《Book on Chinese herbal medicine asks former》Record：" fruit of Chinese magnoliavine, for cough key medicine, all cough due to wind-cold evil,
Cough due to summer-heat evil, cough due to dryness, epersalgia cough, kidney water void are coughed, the fiery void of kidney is coughed, chronic cough syndrome characterized by dyspnea ... is all with it ".Zhang Zhongjing clearly refers to
Go out：All persons of coughing can add the fruit of Chinese magnoliavine.《Pharmacopoeia of People's Republic of China》Carrying it is used for " chronic cough and dyspnea of deficiency type ... ... palpitation and insomnia ".
The fruit of Chinese magnoliavine is widely used in the cough due to deficiency of the lung's illness of the dry cough without phlegm or chronic cough in cough later stage endlessly on tcm clinical practice.
The chemical composition of the fruit of Chinese magnoliavine is mainly volatile oil, lignanoids, triterpenes, organic acid and polysaccharide, wherein
Cyclohexyl biphenyl octene lignanoids and drop triterpene lactone constituents are the characteristic chemical constituents of schisandra plant.Fruit of Chinese magnoliavine pharmacological activity
Extensively, relevant report is numerous, especially in terms of its protective effect and antitoxic heart-soothing and sedative effect to liver, studies more.
Lignan component is the class important component in schisandra chinensis medicinal material, and the research about its liver protection function is reported
At most, in addition it is reported that the effects such as schisandra lignan component also has antitumor, AntiHIV1 RT activity, anti-gastric-ulcer, anti-inflammatory.But,
Total lignan as in schisandra chinensis medicinal material and its important element of the first species, having no on it whether there is alleviation effect to cough always
Document report.
The content of the invention
It is an object of the invention to provide the new application of fructus schizandrae total lignans, it is characterized in particular in providing fructus schizandrae total lignans
New application in the medicine for preparing treatment cough.
Further, the present invention provides fructus schizandrae total lignans and prepared for treating acute, subacute or chronic cough
Medicine in new application.
Further, the present invention also provides fructus schizandrae total lignans and is preparing for antibechic, alleviation cough and eliminating air flue
Application in the medicine of inflammation.
The fructus schizandrae total lignans, extract from schisandra chinensis medicinal material and obtain, and extract obtained fruit of Chinese magnoliavine hammer butt fat
Lignan component content is 50%~100% (quality) in element.
Contained lignan component includes deoxyschizandrin, schizandrin A, the fruit of Chinese magnoliavine in fructus schizandrae total lignans
C prime, schizandrin, wuweizi alcohol B, Schisantherin C and schisantherin the second grade.
Described schisandra chinensis medicinal material can be the fruit of Chinese magnoliavine Schisandra chinensis (Turcz.) Baill. (i.e. northern five
Taste) and/or schisandra chinensis Schisandra sphenanthera Rehd.et Wils. (i.e. kadsura longepedunculata).
Fructus schizandrae total lignans can be passed through the existing preparation process system of the art by those skilled in the art
Into pharmaceutically acceptable formulation, the formulation be such as, but not limited to tablet, hard shell capsules, soft capsule, powder, tincture, oral liquid,
Syrup, granule, pill or injection.
The fructus schizandrae total lignans of the present invention are extracted using the existing conventional method of the art from schisandra chinensis medicinal material
Obtain.For example, the method that is disclosed in can refer to Application No. CN201110020423 patent application prepares fruit of Chinese magnoliavine hammer butt
Fat element：With 70% ethanol (contain 2% Tween 20) of 10 times of amounts fruit of Chinese magnoliavine that refluxing extraction is crushed 2 times, 1 hour every time, close
And extract solution, it is concentrated under reduced pressure, concentrate is extracted with ethyl acetate 3 times, collects ethyl acetate layer, after being concentrated under reduced pressure, plus suitable quantity of water
Dilution, upper XAD-4 resins, first with distillation water elution, then use 70% ethanol elution, collect 70% ethanol elution part, decompression
Concentration, carries out vacuum spray drying afterwards.
The present invention is stimulated using smoke from cigarette for the clinical treatment present situation and difficult point of cough and causes Cough reflex sensitivity to increase globefish
Mouse model and citric acid smoke stimulation cause acute cough's guinea pig model to be tested, and as a result show, fructus schizandrae total lignans energy
Significantly extension smoke from cigarette, which stimulates cause Cough reflex sensitivity to increase cavy and citric acid, stimulates the cough for causing acute cough cavy to hide
Phase, reduction cough number of times, substantially reducing smoke from cigarette stimulates cause Cough reflex sensitivity to increase inflammatory cell in cavy bronchoalveolar lavage fluid
Sum and neutrophil leucocyte ratio, cavy peribronchiolitis disease is thin after pathology section examination prompting fructus schizandrae total lignans are intervened
Born of the same parents' infiltration is significantly reduced, and mitigation is oozed out in tube chamber, and the broadening degree of alveolar septum mitigates, and points out fructus schizandrae total lignans to cavy
Airway inflammation has significant inhibitory action.Alone schizandrin A, deoxyschizandrin and Schisantherin C without remarkable effect, and
And the effect of fructus schizandrae total lignans is significantly better than fruit of Chinese magnoliavine water extract, and in certain dose-effect relationship, antibechic, alleviation are shown
Application prospect in terms of cough and elimination airway inflammation.
Brief description of the drawings
Fig. 1, is the guinea pig lung tissue of embodiment one and air flue pathological section representative graph (HE × 200),
Fig. 2, is influence of the fructus schizandrae total lignans different time points to citric acid smoke stimulation guinea pig cough's number of times.
Embodiment
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but the present invention is not limited thereto.
Experimental animal used in specific embodiment：Pure white Hartly cavys, regular grade, male, 300 ± 50g of body weight, extensively
East saves Experimental Animal Center and provides (SCXK (Guangdong) 2008-0002).Cavy is raised in relative clean, peace and quiet, constant temperature (23 ± 3
DEG C), in constant humidity (55 ± 15%) environment, day and night the cycle is 12:12 hours/day, sub-cage rearing, can freely be eaten by 5/cage
Thing and water.
Medicine, reagent and instrument used in specific embodiment：
1) fructus schizandrae total lignans, its preparation process is：
Schisandra chinensis medicinal material is crushed, with solid-liquid ratio 1:10 70% ethanol (Tween 20 for containing 2%) refluxing extraction 2 times, often
Secondary 1 hour, merge extract solution, be concentrated under reduced pressure, concentrate is extracted with ethyl acetate 3 times, collect ethyl acetate layer, be concentrated under reduced pressure
Afterwards, plus suitable quantity of water dilution, upper XAD-4 resins, first with distillation water elution, then use 70% ethanol elution, collect 70% ethanol and wash
De- part, is concentrated under reduced pressure, and it is 83% then to carry out lignanoid's content in vacuum spray drying, products therefrom.
2) fruit of Chinese magnoliavine water extract, its preparation process is：
Schisandra chinensis medicinal material crushes → 8 times of amount decoctings and boils 2h, and the concentration of 3 times → decoction liquor, the water extraction of the drying → fruit of Chinese magnoliavine are decocted altogether
Take thing；
3) schizandrin A, deoxyschizandrin and Schisantherin C：Shenyang Kai Di Science and Technology Ltd.s.0.9% sodium chloride
Parenteral solution：Dongguan Pu Ji pharmaceutcal corporation, Ltds.Yellow Jackets：Merck companies of the U.S..Codeine：Chinese medicines group industry share
Co., Ltd." red rose " board cigarette with filter tip：Guangzhou Zhong Yan Industrial Co., Ltd.Other conventional reagents：Guangzhou Chemical Reagent Factory.
4) laboratory apparatus：PM type single-chamber certain non-limiting examples petty action objects retouch instrument (1.0L)：Buxco companies of the U.S.；Digital photography
Integral system：Japanese Nikon companies；0.6m × 0.6m × 1m smoke from cigarette toxicant exposure boxes：Make by oneself in this laboratory；A1003 electronics
Balance：German Satorius companies；MDF-U53V-80 DEG C of low temperature refrigerator：SANYO GS company；3-18K SIGMA are freezed at a high speed
Centrifuge：Beckman companies of the U.S.；22G venous detaining needles：Suzhou Medical Devices Co., Ltd.；Anke TGL-16B types are common
Supercentrifuge：Town in Shanghai stops scientific instrument factory；The desk-top refrigerated centrifuge of 400 types：German Heraeus companies；XW80A type vortexs
Oscillator：Shanghai precision instrumentation Co., Ltd；DK8A thermostat water baths：The upper grand test apparatus Co., Ltd of Nereid.
All data are represented with " means standard deviation " in embodiment, are compared between each group and are carried out using spss13.0
One-way analysis of variance, variance uses least significant difference method (LSD) together, and heterogeneity of variance or nonnormal data are examined using sum of ranks
Test, P ＜ 0.05 represent that difference is statistically significant.
Embodiment one：Fructus schizandrae total lignans stimulate smoke from cigarette the pharmacological action for causing Cough reflex sensitivity to increase cavy
1.1 fume smoking method：Cavy is placed in self-control cigarette toxicant exposure box, often after adaptability peace and quiet are raised one week before experiment
It is secondary to light 10 cigarettes in (fire-cured tobacco type, tar content 12mg, smoking nicotine content 1.1mg, carbon monoxide in flue gas contains in sootiness groove
Measure 15mg), smoke from cigarette is squeezed into toxicant exposure box by triple valve, the timing since the cigarette burning-out.Each fumigation 20 minutes, often
Its fumigation 2 times, is more than 6 hours, continuous fumigation 14 days per secondary fumigation interval time.
1.2 experiment：
Cavy completely random is divided into normal group, model group, solvent control group (0.5% PEG400), codeine group, water extraction
Take thing high dose group (dosage 500mg/kg cavys/day, drug concentration 50mg/mL), total lignan high dose group (dosage 500mg/
Kg cavys/day, drug concentration 50mg/mL), total lignan middle dose group (dosage 250mg/kg cavys/day, drug concentration 25mg/
ML), total lignan low dose group (dosage 125mg/kg cavys/day, drug concentration 12.5mg/mL), schizandrin A high dose
Group (dosage 500mg/kg cavys/day, drug concentration 50mg/mL), deoxyschizandrin high dose group (dosage 500mg/kg cavys/
My god, drug concentration 50mg/mL) and Schisantherin C high dose group (dosage 500mg/kg cavys/day, drug concentration 50mg/mL).
In addition to normal group, remaining each group animal is stimulated using the fume smoking method in above-mentioned 1.1.Except normal group and codeine
Group is outer, and remaining each group cavy is from sootiness daystart, in 2 hours corresponding medicines of orally administration before second daily of sootiness
Or solvent, continuous 14 days.Codeine group checks that (30mg/kg cavys, can for oral administration first 1 hour in citric acid Cough reflex sensitivity
Treat because of concentration 3mg/mL).Normal group is normally raised, and does not make any processing.Cavy is placed in body and retouched in case within 15th day, adapt to 2min
Afterwards, atomization 0.4mol/L citric acids progress cough is excited, and atomization terminates after 10min, continues to observe 10min, record certainly open by atomization
Guinea pig cough's total degree and cough latent period in the 20min of beginning.
After excitation experiment of coughing 24h, 3% Nembutal sodium solution (1mL/kg) intraperitoneal injection of anesthesia animal, heart extracting blood
10mL.The PBS of 6mL 0.1mol/L precoolings is taken, point 3 progress alveolar wasses, the left lung of unified lavation is filled repeatedly every time
Wash 3 times, obtain bronchoalveolar lavage fluid (Bronchoalveolar Lavage Fluid, BALF).Gained BALF is shaken and is suspended, is extracted
0.5mL, is fully cracked with erythrocyte cracked liquid, and 3000 revs/min centrifuge 10 minutes, take 10 μ L of supernatant drops to enter blood count
Total (the TCS/mL=(four big lattice TCS/4) × 10 of BALF inflammatory cells is calculated under plate, light microscope4/mL)；
Extract remaining BALF after 0.5mL and centrifuge 10min in 3000rpm, precipitation is suspended with 1mL PBS, take 100 μ L to make cell and apply
Piece, natural air drying is soaked in 10% neutral formalin and fixed overnight, carries out flowing water after taking-up successively and rinses 10min, bush uniformly dyeing
Color 15sec, flowing water rinse 1min, 1% hydrochloride alcohol decolouring 2sec, flowing water and rinse 10min, eosin stains 5sec, flowing water flushing
10min, drying, obtain and 20 400 times of visuals field progress continuous counters are continuously randomly selected under neutral gum mounting, light microscope,
400 cells of every smear continuous counter, calculate the ratio of wherein neutrophil leucocyte, eosinophils, macrophage, lymphocyte
Example.
Cavy is extracted after BALF, carries out lavation from heart injection 50mLPBS, 2.5mL4% paraformaldehydes are injected from tracheae,
Then one piece of bottom right lung tissue of clip and one section of tracheae, 10% neutral formalin fix more than 24h.Take out the lung group fixed
Knit, Gradient elution using ethanol, biological clarifier processing, waxdip, embedding, section, dewaxing, graded ethanol aquation, double steamings are carried out successively
The of short duration rinsing of water, is finally carried out after HE dyeing, neutral gum mounting, carries out pathological observation.
Experimental result：Compared with normal group, each experimental group Guinea Pig Airway resistance has no notable difference, points out this Experimental modeling
Method does not cause the increase of Guinea Pig Airway resistance, is different from COPD animal model.
Each experimental group cavy citric acid excites cough number of times to be shown in Table 1.As a result show, compared with model group, total lignan
(high, medium and low dosage group) can substantially reduce the cough number of times of model guinea pigs, and show certain dosage correlation；With mould
Type group compares, and water extract high dose group, schizandrin A high dose group, deoxyschizandrin high dose group and Schisantherin C are high
Dosage group guinea pig cough's number of times is without significant difference.
Each experimental group of table 1 to smoke from cigarette stimulate cause Cough reflex sensitivity increase model guinea pigs cough times influence ()
(n=7~10)
Note：Compared with model group：*P<0.05, * * P<0.01
Each experimental group cavy citric acid cough excitation experiment cough latent period is shown in Table 2.As a result show, compared with model group,
The high, medium and low dosage intervention group cough latent period of total lignan significantly extends；Water extract, schizandrin A, deoxyschizandrin
Guinea pig cough is not made significant difference in incubation period with Schisantherin C high dose.
Each experimental group of table 2 on smoke from cigarette stimulate cause Cough reflex sensitivity increase model guinea pigs cough latent period influence () (n=7~10)
Note：Compared with model group：*P<0.05, * * P<0.01
Inflammatory cell sum and classification comparative experiments the results are shown in Table 3 in each experimental group BALF.As a result show, with model group ratio
Compared with the high, medium and low dosage of total lignan can substantially reduce inflammatory cell sum in BALF；The height of total lignan, middle dosage can show
Write the ratio for reducing neutrophil leucocyte in BALF.Compared with model group, water extract, schizandrin A, deoxyschizandrin and five
Taste ester first high dose group cavy BALF TCSs and classified counting of leucocyte are with model group without significant difference.
Each experimental group of table 3 increases the BAL fluid inflammatory cell sum of model guinea pigs to chronic cough sensitiveness
With the effect of classification () (n=7~10)
Note：Compared with model group：*P<0.05, * * P<0.01
Pathology section examination result shows, is compared with model group, each dosage group guinea pig lung tissue of fructus schizandrae total lignans and
Tracheae pathology is obviously improved：Cavy peribronchiolitis disease cellular infiltration is significantly reduced, and mitigation, alveolar septum are oozed out in tube chamber
Broadening degree mitigates, and points out fructus schizandrae total lignans to have the obvious effect for mitigating lung and airway inflammation.And water extract, five
Taste A prime, deoxyschizandrin and Schisantherin C high dose group guinea pig lung tissue and tracheae pathology improve unobvious.Guinea pig lung
Tissue and tracheae pathological section representative graph are shown in accompanying drawing 1.
Embodiment one test result indicates that, fructus schizandrae total lignans to smoke from cigarette stimulate cause Cough reflex sensitivity increase globefish
Mouse tool is significantly reduced cough number of times, extension cough latent period, the effect for mitigating lung and airway inflammation.
Embodiment two：
After cavy rests one week, Cough reflex sensitivity screening is carried out：The atomization of 0.8mol/L citric acids stimulates 1min, stops mist
Change, continue observe 5min, record from atomization start 6min in cough number of times, more than 10 times less than 50 times cavy be qualified globefish
Mouse.
The cavy completely random for screening qualified is divided into normal group, solvent control group (0.5% PEG400), codeine
Group, water extract high dose group (dosage 500mg/kg cavys/day, drug concentration 50mg/mL), total lignan high dose group (agent
Measure 500mg/kg cavys/day, drug concentration 50mg/mL), total lignan middle dose group (dosage 250mg/kg cavys/day, medicine
Concentration 25mg/mL), total lignan low dose group (dosage 125mg/kg cavys/day, drug concentration 12.5mg/mL), fruit of Chinese magnoliavine first
Plain high dose group (dosage 500mg/kg cavys/day, drug concentration 50mg/mL), deoxyschizandrin high dose group (dosage 500mg/
Kg cavys/day, drug concentration 50mg/mL) and Schisantherin C high dose group (dosage 500mg/kg cavys/day, drug concentration
50mg/mL).In addition to normal group and codeine group, remaining each group cavy continuous 5 days daily orally administration medicines or solvent, 1 time/
My god, 1h progress citric acid cough is excited after administration on the 5th or solvent：The atomization of 0.8mol/L citric acids stimulates 1min, stops mist
Change, continue to observe 5min, cough number of times of the record from be atomized in 6min.Codeine group was excited in citric acid cough on the 5th
Preceding 1 hour oral administration.Normal group is normally raised, and is directly carried out citric acid within 5th and is excited.
The cough number of times of each experimental group is as shown in table 5.As a result show, compared with normal group, high, medium and low dose of total lignan
Guinea pig cough's number of times of amount intervention group is substantially reduced, and water extract, schizandrin A, deoxyschizandrin and Schisantherin C are high
Dosage group guinea pig cough's number of times is without significant difference.
Each experimental group citric acid of table 5 cause acute cough cavy cough number of times () (n=8)
Note：Compared with normal group group：*P<0.05, * * P<0.01
The cough latent period of each experimental group cavy is as shown in table 6.As a result show, compared with normal group, total lignan height,
In, the cough latent period of low dosage intervention group cavy significantly extend, water extract, schizandrin A, deoxyschizandrin and five
Taste ester first high dose intervention group guinea pig cough's incubation period is without significant difference.
Each experimental group citric acid of table 6 cause acute cough cavy cough latent period () (n=8)
Note：Compared with normal group：*P<0.05, * * P<0.01
The result of embodiment two illustrates that fructus schizandrae total lignans can significantly reduce citric acid smoke stimulation and cause acute cough globefish
The cough number of times of mouse, extension cough latent period, show the application potential in terms for the treatment of acute cough.
Embodiment three
After cavy rests one week, Cough reflex sensitivity screening is carried out：The atomization of 0.8mol/L citric acids stimulates 1min, stops mist
Change, continue observe 5min, record from atomization start 6min in cough number of times, more than 10 times less than 50 times cavy be qualified globefish
Mouse.
After the qualified cavy of screening is normally raised 3 days, 4 big groups are randomly divided into, per big group 30.First big group is randomly divided into
3 groups, per group 10, directly carry out citric acid cough and excite：The atomization of 0.8mol/L citric acids stimulates 1min, stops mist
Change, continue to observe 5min, cough number of times of the record from be atomized in 6min.Second largest group is randomly divided into 3 groups：Normal group,
Codeine group (30mg/kg, oral administration), (250mg/kg, drug concentration 25mg/mL, orally gives fructus schizandrae total lignans group
Medicine), per group 10, normal group directly carries out citric acid cough and excited, and codeine group and the administration 1 of fructus schizandrae total lignans group are small
When after carry out cough and excite, shooting condition is with first big group；The third-largest group and the fourth-largest group of packet and shooting condition are with
Two organize greatly identical, and codeine group and fructus schizandrae total lignans group administration time are respectively 3h and 5h before exciting.As a result such as Fig. 2 institutes
Show, show that citric acid smoke stimulation can be substantially reduced after fructus schizandrae total lignans (250mg/kg) once daily 1h causes cavy
Acute cough's number of times, and after administration 5h remain to show significant drug effect, and codeine after administration 5h cough number of times with
Normal group is without significant difference.
The result of study of embodiment 1~3 shows that fructus schizandrae total lignans, which can significantly extend smoke from cigarette, stimulates cause cough quick
Perception, which increases cavy and citric acid, to stimulate and causes the cough latent period of acute cough cavy, reduces cough number of times, substantially reduces cigarette
Smoke stimulation causes Cough reflex sensitivity to increase inflammatory cell sum and neutrophil leucocyte ratio, pathological section in cavy bronchoalveolar lavage fluid
Cavy peribronchiolitis disease cellular infiltration is significantly reduced after observation prompting fructus schizandrae total lignans intervention, is oozed out and is subtracted in tube chamber
Gently, the broadening degree of alveolar septum mitigates, and points out fructus schizandrae total lignans to have significant inhibitory action to the airway inflammation of cavy.
Alone schizandrin A, deoxyschizandrin and Schisantherin C are without remarkable effect, and the effect of fructus schizandrae total lignans is obvious
It is better than fruit of Chinese magnoliavine water extract, and in certain dose-effect relationship, answering in terms of showing antibechic, alleviate cough and eliminating airway inflammation
Use prospect.
Example IV (preparation example of fructus schizandrae total lignans syrup)
By 2kg fructus schizandrae total lignans, fructus schizandrae total lignans solution is made with suitable quantity of water dissolving, it is standby；Separately take sucrose
2kg, adds water and boils, the fructus schizandrae total lignans solution prepared before addition, and sodium benzoate 4g, mixes, and stands, takes
Clear liquid, adds water to 2000mL, mixes, and the syrup of fructus schizandrae total lignans, every bottle of 100mL packing is made.
Instructions of taking：Daily 1~3 time, each 10mL, serious patient can take the circumstances into consideration dosage.
The fructus schizandrae total lignans of the present embodiment are made using previously described preparation process.
Application examples
Syrup made from implementing four passes through clinical trial, wherein having chronic cough 15 and acute cough 10, patient is every
Day drinks syrup 1~3 time, and each 10mL continuously takes 1~2 week, total effective rate is 100%, concrete outcome is by shown in following table.
| Case | It is effective | Effectively | It is invalid |
| Acute cough | 8 | 2 | 0 |
| Chronic cough | 10 | 5 | 0 |
Just each and every one wherein several model cases describe in detail below：
Case 1：Huang, man coughs 1 year or so, based on dry cough, and items check normal, is diagnosed as the high quick synthesis of cough
Levy.Take 2 bottles of fructus schizandrae total lignans syrup, start within the 2nd day work, cough take a turn for the better 5 into, add after 2 bottles, cough take a turn for the better 9 into,
Without recurrence.
Case 2：Lee, female 24 years old, coughs January, is diagnosed as postinfectious cough, takes fructus schizandrae total lignans syrup 2
Bottle, takes medicine second day and works, cough frequency is substantially reduced, added after 2 bottles, cough symptom is substantially eliminated.
Case 3：Rely certain, man 27 years old, coughs more than 1 year, is diagnosed as postinfectious cough, takes fructus schizandrae total lignans syrup 3
Bottle, medication daystart is worked, and cough frequency is reduced, and degree is remarkably decreased, and switching to monophone by paroxysmal cough coughs, 3 bottles of clothes
After being finished, cough is completely eliminated.
Case 4：It is tall and erect certain, female, 56 years old, cough, expectoration more than 10 years were diagnosed as chronic bronchitis, Eosinophilic
Bronchitis, takes 2 bottles of fructus schizandrae total lignans syrup, takes medicine second day and works, and cough takes a turn for the better 7 into adding after 2 bottles, cough
Substantially eliminate, follow-up is without recurrence after March.
Case 5：5 certain, man 33 years old, coughs more than 4 years, has a little phlegm viscous in vain, is diagnosed as the high quick syndrome of cough.Take five
2 bottles of taste total lignan syrup, take medicine second day work, cough take a turn for the better 4 into, substantially without phlegm, add after 2 bottles, cough disappear substantially
Remove.
As seen from the above-described embodiment, cough just can effectively only be alleviated by oral fructus schizandrae total lignans syrup, mitigates gas
Road inflammation, moreover, fructus schizandrae total lignans extract from Chinese medicine Schisandra chinensis, the fruit of Chinese magnoliavine is Ministry of Public Health's announcement available for health food
Chinese medicine, to human body without any toxicity and side effect.
Fructus schizandrae total lignans are in addition to being made syrup, and those skilled in the art can also use existing preparation as needed
Technique is made into other pharmaceutically acceptable formulations, such as tablet, hard shell capsules, soft capsule, powder, tincture, pill, particle
Agent, injection or other oral liquid formulations etc..Granule can for example be made by the following method：By fructus schizandrae total lignans
Mixed with supplementary product starch, sucrose and disintegrant, then feed the mixture into the plain derivative of adhesive fiber dissolved with water
Mixed in solution, medicine be made by soft grain using extrusion granulator method, through drying, sieving, oversize suitably crush, after
Sieve, can be made into single-size.Also tablet can be made by the following method：By fructus schizandrae total lignans and appropriate amount of starch, talcum powder
Mixing, is moistened with 70% ethanol, particle is made, then with tabletting machine, so that fructus schizandrae total lignans piece is made.It can also lead to
Cross and appropriate carboxymethyl cellulose, cyclodextrin are added into fructus schizandrae total lignans, to prepare fructus schizandrae total lignans capsule.These
Preparation process is the art prior art, and this is no longer going to repeat them.
The above described is only a preferred embodiment of the present invention, any formal limitation not is done to the present invention, therefore
All contents without departing from technical solution of the present invention, the technical spirit according to the present invention any is simply repaiied to made for any of the above embodiments
Change, equivalent variations and modification, in the range of still falling within technical solution of the present invention.
Claims (8)
1. fructus schizandrae total lignans are being prepared for treating the application in the medicine coughed.
2. application according to claim 1, it is characterised in that the medicine is acute, subacute or chronic for treating
The medicine of cough.
3. application according to claim 1, it is characterised in that the medicine is for antibechic, alleviates cough or elimination gas
The medicine of road inflammation.
4. the application according to claims 1 to 3 any one, it is characterised in that the fructus schizandrae total lignans are from five
Extract what is obtained in taste.
5. application according to claim 4, it is characterised in that the fructus schizandrae total lignans wherein contain 50~100%
Lignan component.
6. application according to claim 4, it is characterised in that the described fruit of Chinese magnoliavine is fruit of Chinese magnoliavine Schisandra
In chinensis (Turcz.) Baill., schisandra chinensis Schisandra sphenanthera Rehd.et Wils. extremely
Few one kind.
7. the application according to claims 1 to 3 any one, it is characterised in that medicine is made in the fructus schizandrae total lignans
Acceptable formulation on.
8. application according to claim 7, it is characterised in that the formulation is tablet, hard shell capsules, soft capsule, powder, tincture
Agent, oral liquid, syrup, granule, pill or injection.
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| CN201410209875.2A CN103977076B (en) | 2014-05-16 | 2014-05-16 | Fructus schizandrae total lignans are being prepared for treating the application in the medicine coughed |
| PCT/CN2015/076068 WO2015172614A1 (en) | 2014-05-16 | 2015-04-08 | Application of fructus schisandrea total lignans in preparation of medicine or nutraceuticals used for treating coughing |
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| CN201410209875.2A CN103977076B (en) | 2014-05-16 | 2014-05-16 | Fructus schizandrae total lignans are being prepared for treating the application in the medicine coughed |
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| Title |
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| 五味子木脂素类药理作用的研究;关亚会等;《黑龙江中医药》;20081231(第6期);第44-45页 * |
| 五味子甲素逆转肿瘤多药耐药的效应及其机制研究;秦小清;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20120715(第7期);第11页倒数第2段第1-3行 * |
| 五味子药效与临床应用研究;向辉等;《医药导报》;20110830;第30卷;第89页右栏3.2作用于呼吸系统 第1-2行 * |
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