CN103977076A - Application of total schisandra lignans in preparation of medicaments or health-care products for treating cough - Google Patents
Application of total schisandra lignans in preparation of medicaments or health-care products for treating cough Download PDFInfo
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Abstract
The invention relates to a new application of total schisandra lignans in preparation of medicaments or health-care products for treating cough, and in particular relates to a new application in preparation of medicaments or health-care products for preventing cough, relieving cough and eliminating airway inflammation. Experiments show that the total schisandra lignans can be used for significantly reducing the cough frequency of cavies suffering from increased cough sensitivity caused by cigarette smoke stimulus and acute cough caused by citric acid smog stimulus, prolonging the cough latency and significantly reducing the airway inflammation of the cavies suffering from increased cough sensitivity caused by cigarette smoke stimulus, so that the total schisandra lignans can be used for preparing the medicaments for preventing cough, relieving cough and eliminating airway inflammation.
Description
Technical field
The invention belongs to biomedicine field, relating to Fructus Schisandrae Chinensis total lignanoid is preparing antitussive, relieving cough and is eliminating the medicine of airway inflammation or the new purposes in health product at the medicine for the preparation for the treatment of cough or the purposes of health product, particularly Fructus Schisandrae Chinensis total lignanoid.
Background technology
Cough is the modal symptom of internal clinic, sees various respiratory system and non-respiratory system disease.Cough itself is a kind of defense mechanism, removes secretions too much in air flue and prevents that foreign body from sucking air flue by mistake.But cough has for a long time had a strong impact on patient's quality of life and caused the psychological burden that patient is serious, individual and public medical and health expenditure have also significantly been increased simultaneously.
According to the course of disease, divide, cough comprises acute cough's (<3 week), subacute cough (3～8 weeks) and chronic cough (>=8 weeks).The treatment of cough is at present all generally employing central antitussive, around property cough medicine and expectorant etc. are treated, and generally can receive good curative effect.Even but still have the cough of part acute and chronic to adopt the central antitussive things such as codeine, and cough still can not be eased, and consequently many acute coughs are developed into chronic cough, and some Chronic Cough Patients courses of disease even reach decades.
Many parts of sick learning of Foreign Epidemic studies show that chronic cough is at general population's sickness rate approximately 9%～33%, the Epidemiological study of 2003 Nian Yixiang Britain shows, chronic cough reaches 12% at the middle age sickness rate of 50～59 years old, and Chronic Cough Patients accounts for breathes special outpatient clinic patient's 20%.In recent years along with the increasing the weight of gradually of air environmental pollution (as PM2.5, PM10 etc.), the prevalence of chronic cough also may continue to rise.Current research is thought and is caused the Etiological of chronic cough to comprise: cough variant asthma, Eosinophilic bronchitis, gastroesophageal reflux induced cough, upper air flue cough syndrome.The cough causing for the above-mentioned cause of disease, follows cough guide and treats accordingly, and most of patient's cough can obviously be alleviated.Yet, still have part Chronic Cough Patients after series comprehensively checks, show no obvious abnormalities, but cough symptom sustainable existence, previously be referred to as chronic idiopathic cough (Chronic idiopathic cough, CIC), its cough symptom treatment is not good, and needleless is to property etiological treatment, is difficult point and the emphasis place in current chronic cough field.Studies have found that chronic idiopathic cough is common with middle age, mainly with flu, be triggering factors, the long-term existence of after this coughing, conventionally extremely responsive to oil smoke, penetrating odor, cold air, smoke from cigarette etc., sometimes even laugh or talk and can bring out cough, showing as Cough reflex sensitivity and obviously increase.For this kind of situation, the chronic cough that Cough reflex sensitivity the is increased high quick syndrome (Cough hypersensitivity syndrome, CHS) that is referred to as to cough.It is the total key feature of the high quick syndrome patient of chronic cough that Cough reflex sensitivity increases extremely.
For the high quick syndromic patient of cough, temporarily available without suitable treatment means at present, mostly by antitussive medicine, maintain treatment.But antitussive medicine, as codeine and dextromethorphan etc., the side effect of various degrees, as constipation, calmness, respiration inhibition etc., thereby limited its use, and partly the high quick syndromic patient of cough even uses central antitussive thing, cough also can not be alleviated, and has a strong impact on daily life quality.
Fructus Schisandrae Chinensis sour in the mouth, sweet, warm in nature.Return lung, the heart, kidney channel.Lung being a delicate viscus, dislike dry, the sweet Wen Errun of Fructus Schisandrae Chinensis, nourishing the lung to arrest cough; Chronic cough causes failure of the kidney in receiving QI, and Fructus Schisandrae Chinensis sour in the mouth convergence helps kidney improving inspiration by invigorating kidney-QI, and chronic cough is that effect is very big due to treatment lung yin virtual loss, failure of the kidney in receiving QI.< < book on Chinese herbal medicine can be compiled > > and record: " chronic cough, should use northern person; Wind and cold, at lung, should be used southern person "; < < medicineization justice > > records: " Fructus Schisandrae Chinensis ... can restrain lung qi, cures mainly asthenia chronic cough "; < < book on Chinese herbal medicine asks former > > to record: " Fructus Schisandrae Chinensis; be cough key medicine, all cough due to wind and cold, cough due to summer-heat affection, the cough due to dryness, epersalgia cough, kidney water void are coughed, kidney fire void is coughed, chronic cough dyspnea with rapid and short breath ... all use it ".Zhang Zhongjing explicitly points out: all persons of coughing all can add Fructus Schisandrae Chinensis.< < Pharmacopoeia of People's Republic of China > > carry its for " chronic cough dyspnea due to deficiency ... palpitation and insomnia ".On tcm clinical practice, Fructus Schisandrae Chinensis is widely used in dry cough without phlegm or chronic cough cough due to deficiency of the lung's disease endlessly in cough later stage.
The chemical composition of Fructus Schisandrae Chinensis is mainly volatile oil, lignanoids, triterpenes, organic acid and polysaccharide, wherein cyclohexyl biphenyl octene lignanoids and fall the characteristic chemical constituent that triterpene lactone constituents is schisandra plant.Fructus Schisandrae Chinensis pharmacologically active is extensive, and relevant report is numerous, and especially it,, to the protective effect of liver and mind tranquilizing and the heart calming effect aspect, studies more.
Lignan component is the class important component in schisandra chinensis medicinal material, and the research report of relevant its liver protection function at most, it is reported that schisandra lignan component also has the effects such as antitumor, anti-HIV, anti-gastric-ulcer, antiinflammatory in addition.But total lignans, as in schisandra chinensis medicinal material and the important element of the first species, has no about it, whether cough there is the bibliographical information of alleviating effect always.
Summary of the invention
The object of the present invention is to provide the new purposes of Fructus Schisandrae Chinensis total lignanoid, be specifically to provide Fructus Schisandrae Chinensis total lignanoid to treat the medicine of cough or the new purposes in health product in preparation.
Further, the invention provides Fructus Schisandrae Chinensis total lignanoid for the preparation for the treatment of acute, subacute or the medicine of chronic cough or the new purposes in health product.
Further, the present invention also provides Fructus Schisandrae Chinensis total lignanoid for the preparation of antitussive, relieving cough and eliminate the medicine of airway inflammation or the application in health product.
Described Fructus Schisandrae Chinensis total lignanoid extracts and obtains from schisandra chinensis medicinal material, and extracting lignan component content in the Fructus Schisandrae Chinensis total lignanoid obtaining is 50%～100% (quality).
In Fructus Schisandrae Chinensis total lignanoid, contained lignan component includes schisandrin B, deoxyschizandrin, schisandrin C, schisandrin, schisantherin B, schisantherin A and schizantherin the second grade.
Described schisandra chinensis medicinal material can be Fructus Schisandrae Chinensis Schisandra chinensis (Turcz.) Baill. (being Radix Schisandrae Bicoloris) and/or schisandra chinensis Schisandra sphenanthera Rehd.et Wils. (being Fructus Schisandrae Sphenantherae).
Those skilled in the art can be made into pharmaceutically acceptable dosage form by the existing preparation process of the art by Fructus Schisandrae Chinensis total lignanoid, and described dosage form is such as but not limited to tablet, hard capsule, soft capsule, powder, tincture, oral liquid, syrup, granule, pill or injection.
Fructus Schisandrae Chinensis total lignanoid of the present invention adopts the existing conventional method of the art to extract and obtain from schisandra chinensis medicinal material.For example, the method disclosing in can the patent application that be CN201110020423 with reference to application number is prepared Fructus Schisandrae Chinensis total lignanoid: the Fructus Schisandrae Chinensis of pulverizing with 70% ethanol (Tween20 containing the 2%) reflux, extract, of 10 times of amounts 2 times, each 1 hour, merge extractive liquid,, concentrating under reduced pressure, concentrated solution is extracted with ethyl acetate 3 times, collect ethyl acetate layer, after concentrating under reduced pressure, add suitable quantity of water dilution, upper XAD-4 resin, first use distilled water eluting, then use 70% ethanol elution, collect 70% ethanol elution part, concentrating under reduced pressure, carries out vacuum spray drying afterwards.
The present invention is directed to clinical treatment present situation and the difficult point of cough, adopting smoke from cigarette to stimulate to cause Cough reflex sensitivity to increase guinea pig model and citric acid smoke stimulation causes acute cough's guinea pig model and tests, result shows, Fructus Schisandrae Chinensis total lignanoid energy significant prolongation smoke from cigarette stimulates and to cause that Cough reflex sensitivity increases Cavia porcellus and citric acid stimulates the cough latent period that causes acute cough Cavia porcellus, reduce cough number of times, the stimulation of remarkable minimizing smoke from cigarette causes Cough reflex sensitivity and increases inflammatory cell sum and neutrophilic granulocyte ratio in Cavia porcellus bronchoalveolar lavage fluid, after the intervention of pathology section examination prompting Fructus Schisandrae Chinensis total lignanoid, Cavia porcellus peribronchiolitis disease cellular infiltration obviously reduces, in tube chamber, ooze out and alleviate, alveolar septum broadening degree alleviates, prompting Fructus Schisandrae Chinensis total lignanoid has significant inhibitory action to the airway inflammation of Cavia porcellus.Alone deoxyschizandrin, schisandrin B and schisantherin A are without remarkable effect, and the effect of Fructus Schisandrae Chinensis total lignanoid is significantly better than Fructus Schisandrae Chinensis water extract, and be a certain amount of effect relationship, show the application prospect of antitussive, relieving cough and elimination airway inflammation aspect.
Accompanying drawing explanation
Fig. 1, is embodiment mono-guinea pig lung tissue and air flue pathological section representative graph (HE * 200),
Fig. 2 is the impact of Fructus Schisandrae Chinensis total lignanoid different time points on citric acid smoke stimulation guinea pig cough number of times.
The specific embodiment
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but the present invention is not limited to this.
laboratory animal used in specific embodiment: pure white Hartly Cavia porcellus, regular grade, male, body weight 300 ± 50g, Guangdong Province's Experimental Animal Center provides (SCXK (Guangdong) 2008-0002).Cavia porcellus is raised in relatively clean, peace and quiet, constant temperature (23 ± 3 ℃), constant humidity (55 ± 15%) environment, and day and night the cycle is 12:12 hour/day, and sub-cage rearing, can freely obtain food and water by 5/cage.
medicine, reagent and instrument used in specific embodiment:
1) Fructus Schisandrae Chinensis total lignanoid, its preparation process is:
Schisandra chinensis medicinal material is pulverized, 70% ethanol (Tween20 containing the 2%) reflux, extract, of use solid-liquid ratio 1:10 2 times, each 1 hour, merge extractive liquid,, concentrating under reduced pressure, concentrated solution is extracted with ethyl acetate 3 times, collect ethyl acetate layer, after concentrating under reduced pressure, add suitable quantity of water dilution, upper XAD-4 resin, first uses distilled water eluting, then uses 70% ethanol elution, collect 70% ethanol elution part, concentrating under reduced pressure, then carries out vacuum spray drying, and in products therefrom, lignanoid's content is 83%.
2) Fructus Schisandrae Chinensis water extract, its preparation process is:
Schisandra chinensis medicinal material is pulverized → 8 times of water gagings and is decocted 2h, decocts altogether 3 times → decoction liquor concentrated, dry → Fructus Schisandrae Chinensis water extract;
3) deoxyschizandrin, schisandrin B and schisantherin A: Shenyang Kai Di Science and Technology Ltd..0.9% sodium chloride injection: Dongguan Pu Ji pharmaceutcal corporation, Ltd.Pentobarbital sodium: U.S. Merck company.Codeine: Industries, Inc of traditional Chinese medicines group." red rose " board cigarette with filter tip: Guangzhou Zhong Yan Industrial Co., Ltd.Other conventional reagent: Guangzhou Chemical Reagent Factory.
4) experimental apparatus: PM type list chamber unrestricted type petty action object is retouched instrument (1.0L): U.S. Buxco company; Digital photography integral system: Japanese Nikon company; 0.6m * 0.6m * 1m smoke from cigarette toxicant exposure box: this laboratory self-control; A1003 electronic balance: German Satorius company; MDF-U53V-80 ℃ of cryogenic refrigerator: SANYO GS company; 3-18K SIGMA High speed refrigerated centrifuge: U.S. Beckman company; 22G venous detaining needle: Suzhou Medical Devices Co., Ltd.; The common high speed centrifuge of Anke TGL-16B type: Town in Shanghai stops scientific instrument factory; The desk-top refrigerated centrifuge of 400 type: German Heraeus company; XW80A type vortex agitator: Shanghai precision instrumentation company limited; DK8A thermostat water bath: go up the grand test apparatus of Nereid company limited.
In the specific embodiment, all data represent with " means standard deviation ", between each group, relatively adopt spss13.0 to carry out one factor analysis of variance, variance is used least significant difference method (LSD) together, heterogeneity of variance or nonnormal data acquisition rank test, P < 0.05 represents that difference has statistical significance.
Embodiment mono-: Fructus Schisandrae Chinensis total lignanoid stimulates and causes the pharmacological action that Cough reflex sensitivity increases Cavia porcellus smoke from cigarette
1.1 fume smoking methods: Cavia porcellus is raised after one week in experiment prospective adaptation is quiet, be placed in self-control medicated cigarette toxicant exposure box, light 10 medicated cigarettes (fire-cured tobacco type in sootiness groove at every turn, tar content 12mg, smoking nicotine content 1.1mg, carbon monoxide in flue gas content 15mg), by three-way valve, smoke from cigarette is squeezed in toxicant exposure box, from medicated cigarette burning-out, started timing.Each fumigation 20 minutes, every day, fumigation was 2 times, and every secondary fumigation is greater than 6 hours interval time, and fumigation is 14 days continuously.
1.2 experiments:
Cavia porcellus completely random is divided into normal group, model group, solvent control group (0.5% PEG400), codeine group, water extract high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL), total lignans high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL), (the dosage 250mg/kg Cavia porcellus/sky of dosage group in total lignans, drug level 25mg/mL), total lignans low dose group (dosage 125mg/kg Cavia porcellus/sky, drug level 12.5mg/mL), deoxyschizandrin high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL), schisandrin B high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL) and schisantherin A high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL).
Except normal group, all the other each treated animals all adopt the fume smoking method in above-mentioned 1.1 to stimulate.Except normal group and codeine group, all the other respectively organize Cavia porcellus from sootiness first day, and the first 2 hours per os of sootiness for the second time every day give corresponding medicine or solvent, continuous 14 days.Codeine group checks first 1 hour in citric acid Cough reflex sensitivity, oral administration (30mg/kg Cavia porcellus, codeine concentration 3mg/mL).Normal group is normally raised, and does not do any processing.Cavia porcellus was placed in to body in the 15th day and retouches in case, adapt to after 2min, atomization 0.4mol/L citric acid is coughed and is excited, and after 10min, atomization finishes, and continues to observe 10min, guinea pig cough's total degree and cough latent period in the 20min that record starts from atomization.
After cough excitation experiment 24h, 3% pentobarbital sodium solution (1mL/kg) intraperitoneal injection of anesthesia animal, heart extracting blood 10mL.Get the PBS buffer of 6mL0.1mol/L pre-cooling, minute carry out alveolar wass 3 times, the left lung of unified lavation, lavation 3 times repeatedly, obtains bronchoalveolar lavage fluid (Bronchoalveolar Lavage Fluid, BALF) at every turn.By gained BALF concussion suspendible, extract 0.5mL, with the abundant cracking of erythrocyte cracked liquid, 3000 revs/min centrifugal 10 minutes, get 10 μ L supernatant and splash into blood cell counting plate, under optical microscope, calculate BALF inflammatory cell sum (total cellular score/mL=(four large lattice total cellular score/4) * 10
4/ mL), after extracting 0.5mL, remaining BALF is in the centrifugal 10min of 3000rpm, precipitation 1mLPBS suspendible, get 100 μ L and make cell smear, natural air drying, be soaked in 10% neutral formalin, spend the night fixing, after taking-up, carry out successively flowing water and rinse 10min, haematoxylin dyeing 15sec, flowing water rinses 1min, 1% hydrochloride alcohol decolouring 2sec, flowing water rinses 10min, Yihong dyeing 5sec, flowing water rinses 10min, dry, obtain neutral gum mounting, under optical microscope, continuous counter is carried out in 20 400 times of visuals field of continuous random extraction, 400 cells of every smear continuous counter, calculate wherein neutrophilic granulocyte, eosinophilic granulocyte, macrophage, lymphocytic ratio.
Cavia porcellus extracts after BALF, injects 50mLPBS carry out lavation from heart, from trachea, injects 2.5mL4% paraformaldehyde, then bottom right lung tissue of clip and one section of trachea, and 10% neutral formalin is fixedly more than 24h.Take out the lung tissue having fixed, carry out successively Gradient elution using ethanol, biological clarifier processing, waxdip, embedding, section, dewaxing, gradient ethanol aquation, the of short duration rinsing of distilled water, finally carry out after HE dyeing, neutral gum mounting, carries out pathological observation.
Experimental result: with normal group comparison, each experimental group Guinea Pig Airway resistance has no notable difference, points out this Experimental Modeling not cause Guinea Pig Airway resistance increment, is different from chronic obstructive pulmonary disease animal model.
Each experimental group Cavia porcellus citric acid excites cough number of times in Table 1.Result shows, with model group comparison, total lignans (high, medium and low dosage group) all can significantly reduce the cough number of times of model guinea pigs, and shows certain dosage correlation; With model group comparison, water extract high dose group, deoxyschizandrin high dose group, schisandrin B high dose group and schisantherin A high dose group guinea pig cough number of times are without significant difference.
Each experimental group of table 1 stimulates and causes the cough times influence that Cough reflex sensitivity increases model guinea pigs smoke from cigarette
(n=7～10)
Note: with model group comparison: * P<0.05, * * P<0.01
Each experimental group Cavia porcellus citric acid cough excitation experiment cough latent period is in Table 2.Result shows, with model group comparison, and the equal significant prolongation of the high, medium and low dosage intervention group of total lignans cough latent period; Water extract, deoxyschizandrin, schisandrin B and schisantherin A high dose do not make significant difference to guinea pig cough incubation period.
Each experimental group of table 2 stimulates and causes the cough latent period impact that Cough reflex sensitivity increases model guinea pigs smoke from cigarette
(n=7～10)
Note: with model group comparison: * P < 0.05, * * P < 0.01
In each experimental group BALF, inflammatory cell sum and classification comparative experiments the results are shown in Table 3.Result shows, with model group comparison, the high, medium and low dosage of total lignans all can significantly reduce inflammatory cell sum in BALF; The height of total lignans, middle dosage can significantly reduce the ratio of neutrophilic granulocyte in BALF.With model group comparison, water extract, deoxyschizandrin, schisandrin B and schisantherin A high dose group Cavia porcellus BALF total cellular score and classified counting of leucocyte and model group are without significant difference.
Each experimental group of table 3 is to the bronchoalveolar lavage fluid inflammatory cell sum of chronic cough Increased sensitivity model guinea pigs and the effect of classification
(n=7～10)
Note: with model group comparison: * P<0.05, * * P<0.01
Pathology section examination result shows, with model group comparison, each dosage group guinea pig lung tissue of Fructus Schisandrae Chinensis total lignanoid and trachea pathology all obviously improve: Cavia porcellus peribronchiolitis disease cellular infiltration obviously reduces, in tube chamber, ooze out and alleviate, alveolar septum broadening degree alleviates, and prompting Fructus Schisandrae Chinensis total lignanoid has the effect that significantly alleviates lung and airway inflammation.And water extract, deoxyschizandrin, schisandrin B and schisantherin A high dose group guinea pig lung tissue and the improvement of trachea pathology are not obvious.Guinea pig lung tissue and trachea pathological section representative graph are shown in accompanying drawing 1.
The experimental result of embodiment mono-shows, Fructus Schisandrae Chinensis total lignanoid stimulates and causes Cough reflex sensitivity and increase the effect that Cavia porcellus has significant reduction cough number of times, extends cough latent period, alleviates lung and airway inflammation smoke from cigarette.
Embodiment bis-:
Cavia porcellus rested after one week, carried out Cough reflex sensitivity screening: the atomization of 0.8mol/L citric acid stimulates 1min, stops atomization, continued to observe 5min, the cough number of times of record in atomization starts 6min, and being greater than and being less than the Cavia porcellus of 50 times for 10 times is qualified Cavia porcellus.
The qualified Cavia porcellus completely random of screening is divided into normal group, solvent control group (0.5% PEG400), codeine group, water extract high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL), total lignans high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL), (the dosage 250mg/kg Cavia porcellus/sky of dosage group in total lignans, drug level 25mg/mL), total lignans low dose group (dosage 125mg/kg Cavia porcellus/sky, drug level 12.5mg/mL), deoxyschizandrin high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL), schisandrin B high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL) and schisantherin A high dose group (dosage 500mg/kg Cavia porcellus/sky, drug level 50mg/mL).Except normal group and codeine group, all the other are respectively organized Cavia porcellus per os continuous 5 day every day and give medicine or solvent, 1 times/day, after administration on the 5th or solvent, 1h carries out citric acid cough and excites: the atomization of 0.8mol/L citric acid stimulates 1min, stop atomization, continue to observe 5min, the cough number of times of record in atomization starts 6min.Codeine group excites first 1 hour oral administration in citric acid cough on the 5th.Normal group is normally raised, and within 5th, directly carries out citric acid and excites.
The cough number of times of each experimental group is as shown in table 5.Result shows, with normal group comparison, guinea pig cough's number of times of the high, medium and low dosage intervention group of total lignans all significantly reduces, and water extract, deoxyschizandrin, schisandrin B and schisantherin A high dose group guinea pig cough number of times are without significant difference.
Each experimental group citric acid of table 5 causes the cough number of times of acute cough Cavia porcellus
(n=8)
Note: with the comparison of normal group group: * P<0.05, * * P<0.01
The cough latent period of each experimental group Cavia porcellus is as shown in table 6.Result shows, with normal group comparison, and the equal significant prolongation of cough latent period of the high, medium and low dosage intervention group of total lignans Cavia porcellus, water extract, deoxyschizandrin, schisandrin B and schisantherin A high dose intervention group guinea pig cough incubation period are without significant difference.
Each experimental group citric acid of table 6 causes the cough latent period of acute cough Cavia porcellus
(n=8)
Note: with normal group comparison: * P<0.05, * * P<0.01
The presentation of results Fructus Schisandrae Chinensis total lignanoid of embodiment bis-can significantly reduce cough number of times, the prolongation cough latent period that citric acid smoke stimulation causes acute cough Cavia porcellus, shows the application potential for the treatment of acute cough aspect.
Embodiment tri-
Cavia porcellus rested after one week, carried out Cough reflex sensitivity screening: the atomization of 0.8mol/L citric acid stimulates 1min, stops atomization, continued to observe 5min, the cough number of times of record in atomization starts 6min, and being greater than and being less than the Cavia porcellus of 50 times for 10 times is qualified Cavia porcellus.
Screen the normal raising of qualified Cavia porcellus after 3 days, be divided at random 4 large groups, 30 of every large groups.First group is divided into 3 groups at random, and 10 of every groups all directly carry out citric acid cough and excite: the atomization of 0.8mol/L citric acid stimulates 1min, stops atomization, continue to observe 5min, the cough number of times of record in atomization starts 6min.Second largest group is divided into 3 groups at random: normal group, codeine group (30mg/kg, oral administration), Fructus Schisandrae Chinensis total lignanoid group (250mg/kg, drug level 25mg/mL, oral administration), 10 of every groups, normal group is directly carried out citric acid cough and is excited, and codeine group and the administration of Fructus Schisandrae Chinensis total lignanoid group were coughed and excited after 1 hour, and shooting condition is with first group; The third-largest group all identical with second largest group with grouping and the shooting condition of the fourth-largest group, and codeine group and Fructus Schisandrae Chinensis total lignanoid group administration time are respectively and excite front 3h and 5h.Result as shown in Figure 2, show that can significantly reduce citric acid smoke stimulation after Fructus Schisandrae Chinensis total lignanoid (250mg/kg) once daily 1h causes Cavia porcellus acute cough number of times, and after administration 5h, still can show significant drug effect, and codeine is coughed after administration 5h, number of times and normal group are without significant difference.
The result of study of embodiment 1～3 shows, Fructus Schisandrae Chinensis total lignanoid energy significant prolongation smoke from cigarette stimulates and to cause that Cough reflex sensitivity increases Cavia porcellus and citric acid stimulates the cough latent period that causes acute cough Cavia porcellus, reduce cough number of times, the stimulation of remarkable minimizing smoke from cigarette causes Cough reflex sensitivity and increases inflammatory cell sum and neutrophilic granulocyte ratio in Cavia porcellus bronchoalveolar lavage fluid, after the intervention of pathology section examination prompting Fructus Schisandrae Chinensis total lignanoid, Cavia porcellus peribronchiolitis disease cellular infiltration obviously reduces, in tube chamber, ooze out and alleviate, alveolar septum broadening degree alleviates, prompting Fructus Schisandrae Chinensis total lignanoid has significant inhibitory action to the airway inflammation of Cavia porcellus.Alone deoxyschizandrin, schisandrin B and schisantherin A are without remarkable effect, and the effect of Fructus Schisandrae Chinensis total lignanoid is significantly better than Fructus Schisandrae Chinensis water extract, and be a certain amount of effect relationship, show the application prospect of antitussive, relieving cough and elimination airway inflammation aspect.
Embodiment tetra-(preparation example of Fructus Schisandrae Chinensis total lignanoid syrup)
By 2kg Fructus Schisandrae Chinensis total lignanoid, by suitable quantity of water, dissolve and make Fructus Schisandrae Chinensis total lignanoid solution, standby; Separately get sucrose 2kg, add water boil, add the Fructus Schisandrae Chinensis total lignanoid solution having prepared above, and sodium benzoate 4g, mix, standing, get supernatant, add water to 2000mL, mix, make the syrup of Fructus Schisandrae Chinensis total lignanoid, every bottle of 100mL subpackage.
Instructions of taking: every day 1～3 time, each 10mL, the person of being in a bad way can take the circumstances into consideration dosage.
The Fructus Schisandrae Chinensis total lignanoid of the present embodiment adopts previously described preparation process to make.
Application examples
Implement four syrup that make through clinical experiment, wherein have chronic cough 15 example and acute cough's 10 examples, patient drinks syrup every day 1～3 time, and each 10mL, takes 1～2 week continuously, and total effective rate is 100%, and concrete outcome is by shown in following table.
| Case | Effective | Effectively | Invalid |
| Acute cough | 8 | 2 | 0 |
| Chronic cough | 10 | 5 | 0 |
Below just wherein several each and every one model cases describe in detail:
Case 1: Huang, man, coughs about 1 year, and dry cough is main, and every inspection is all normal, is diagnosed as the high quick syndrome of cough.Take 2 bottles, Fructus Schisandrae Chinensis total lignanoid syrup, within the 2nd day, start onset, cough takes a turn for the better 5 one-tenth, adds after 2 bottles, and cough takes a turn for the better 9 one-tenth, without recurrence.
Case 2: Lee, female, 24 years old, cough January, be diagnosed as postinfectious cough, take 2 bottles, Fructus Schisandrae Chinensis total lignanoid syrup, the second day onset of taking medicine, cough frequency significantly reduces, and adds after 2 bottles, and cough symptom is eliminated substantially.
Case 3: rely certain, man, 27 years old, coughs more than 1 year, be diagnosed as postinfectious cough, take 3 bottles, Fructus Schisandrae Chinensis total lignanoid syrup, the first day of taking medicine starts onset, and cough frequency reduces, degree significantly declines, by paroxysmal cough, transfer monophone to and cough, 3 bottles taken after, cough is eliminated completely.
Case 4: tall and erect certain, female, 56 years old, cough, expectoration more than 10 years, be diagnosed as chronic bronchitis, eosinophilic granulocyte's property bronchitis, take 2 bottles, Fructus Schisandrae Chinensis total lignanoid syrup, the second day onset of taking medicine, cough takes a turn for the better 7 one-tenth, add after 2 bottles, cough is eliminated substantially, follows up a case by regular visits to without recurrence after March.
Case 5: 5 certain, man, 33 years old, cough more than 4 years, have a little in vain sticky expectorant, be diagnosed as the high quick syndrome of cough.Take 2 bottles, Fructus Schisandrae Chinensis total lignanoid syrup, the second day onset of taking medicine, cough takes a turn for the better 4 one-tenth, substantially without expectorant, adds after 2 bottles, and cough is eliminated substantially.
As seen from the above-described embodiment, only, by just effective relieving cough of oral Fructus Schisandrae Chinensis total lignanoid syrup, alleviate airway inflammation, and, Fructus Schisandrae Chinensis total lignanoid extracts from Chinese medicine Schisandra chinensis, and Fructus Schisandrae Chinensis is the Chinese medicine that can be used for health food that Ministry of Public Health is announced, to human body without any toxicity and side effect.
Fructus Schisandrae Chinensis total lignanoid is except making syrup, those skilled in the art also can adopt existing preparation process to be made into pharmaceutically acceptable other dosage forms, for example tablet, hard capsule, soft capsule, powder, tincture, pill, granule, injection or other oral liquid formulations etc. as required.For example granulation agent by the following method: Fructus Schisandrae Chinensis total lignanoid and supplementary product starch, sucrose and disintegrating agent are mixed, again mixture is added with mixing in water-soluble adhesive fiber element derivative solution, adopt extrusion granulator method that medicine is made to soft grit, drying, sieve, oversize is suitably pulverized, after sieve, can be made into single-size.Also can make by the following method tablet: Fructus Schisandrae Chinensis total lignanoid and appropriate amount of starch, Pulvis Talci are mixed, and moistening with 70% ethanol, granulation, then uses tablet machine tabletting, thereby makes Fructus Schisandrae Chinensis total lignanoid sheet.Also can, by add appropriate carboxymethyl cellulose, cyclodextrin in Fructus Schisandrae Chinensis total lignanoid, prepare Fructus Schisandrae Chinensis total lignanoid capsule.These preparation process are the art prior art, and this is no longer going to repeat them.
The above, it is only preferred embodiment of the present invention, not the present invention is done to any pro forma restriction, the content that does not depart from technical solution of the present invention therefore all, according to technical spirit of the present invention, to any simple modification made for any of the above embodiments, equivalent variations and modification, all still belong in the scope of technical solution of the present invention.
Claims (8)
1. Fructus Schisandrae Chinensis total lignanoid is in the medicine for the preparation for the treatment of cough or the application in health product.
2. application according to claim 1, is characterized in that, described medicine or health product are medicine or the health product that are used for the treatment of acute, subacute or chronic cough.
3. application according to claim 1, is characterized in that, described medicine or health product are medicine or the health product for antitussive, relieving cough or elimination airway inflammation.
4. according to the application described in claim 1～3 any one, it is characterized in that, described Fructus Schisandrae Chinensis total lignanoid extracts and obtains from Fructus Schisandrae Chinensis.
5. application according to claim 4, is characterized in that, described Fructus Schisandrae Chinensis total lignanoid wherein contains 50～100% lignan component.
6. application according to claim 4, is characterized in that, described Fructus Schisandrae Chinensis is at least one in Fructus Schisandrae Chinensis Schisandra chinensis (Turcz.) Baill., schisandra chinensis Schisandra sphenanthera Rehd.et Wils..
7. according to the application described in claim 1～3 any one, it is characterized in that, described Fructus Schisandrae Chinensis total lignanoid is made pharmaceutically acceptable dosage form.
8. application according to claim 7, is characterized in that, described dosage form is tablet, hard capsule, soft capsule, powder, tincture, oral liquid, syrup, granule, pill or injection.
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| 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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| 关亚会等: "五味子木脂素类药理作用的研究", 《黑龙江中医药》 * |
| 向辉等: "五味子药效与临床应用研究", 《医药导报》 * |
| 秦小清: "五味子甲素逆转肿瘤多药耐药的效应及其机制研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
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| WO2015172614A1 (en) * | 2014-05-16 | 2015-11-19 | 广州医科大学附属第一医院 | Application of fructus schisandrea total lignans in preparation of medicine or nutraceuticals used for treating coughing |
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