CN103251690B - The sub-volatile oil of dimension medicine nigella glandulifera Freyn is in the application of preparation treatment chronic obstructive pulmonary disease - Google Patents
The sub-volatile oil of dimension medicine nigella glandulifera Freyn is in the application of preparation treatment chronic obstructive pulmonary disease Download PDFInfo
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- CN103251690B CN103251690B CN201310060019.0A CN201310060019A CN103251690B CN 103251690 B CN103251690 B CN 103251690B CN 201310060019 A CN201310060019 A CN 201310060019A CN 103251690 B CN103251690 B CN 103251690B
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Abstract
<b> the present invention relates to NGS volatile oil medical art, that a kind of sub-volatile oil of medicine nigella glandulifera Freyn of tieing up is in the application preparing treatment chronic obstructive pulmonary disease, NGS volatile oil of the present invention has more stable anti-chronic inflammatory disease effect to the chronic bronchitis caused by chronic obstructive pulmonary disease, </b><bGreatT.Gre aT.GT effectively can improve the lung bronchospasm symptoms that </b><bGreatT.Gre aT.GT chronic obstructive pulmonary disease causes simultaneously, stop and form pulmonary belb and emphysema.Its mechanism of action relates to the function suppressing pulmonary branches tracheal smooth muscle M cholinoceptor, reduce pulmonary branches tracheal tissue inflammatory cell and inflammatory cytokine, still belongs to the first time in research both at home and abroad at present.</b>
Description
Technical field
The present invention relates to NGS volatile oil medical art, is that a kind of sub-volatile oil of medicine nigella glandulifera Freyn of tieing up is in the application preparing treatment chronic obstructive pulmonary disease.
Background technology
Chronic obstructive pulmonary disease (chronic obstructive pulmonary dise-ase, COPD) is a kind of general designation of CAO disease, mainly refers to chronic bronchitis and emphysema two kinds of diseases with irreversibility airway obstruction.COPD patient prognosis mala, finally dies from respiratory failure and pulmonary disease, is the fourth-largest disease causing human death.COPD pathogenesis is lung bronchial chronic inflammation mainly, causes the sustainable existence of bronchospasm state, cathepsin hyperfunctioning, and long term makes pulmonary branches tracheal tissue structural damage.Also do not have at present medicine can change pulmonary function Progressive symmetric erythrokeratodermia to decline this trend.The chemicals of COPD symptomatic treatment comprises: glucocorticoid, bronchodilator, antioxidant, antibacterial, expectorant etc., but because chemicals side effect is larger, unsuitable long-term taking (Zhong Nanshan, Yao Wanzhen, Xu Yongjian. chronic obstructive pulmonary disease. the first edition. medical publishing society of Peking University .2007:497-508); Market there is no the Chinese patent medicine for treatment COPD; Inconvenience taken by Chinese medicine decoction, reduces the compliance of patient.Thus, new treatment COPD medicine is found imperative.
Nigella damascena L. platymiscium belongs to ranunculaceae plant Flos Trollii subfamily, wherein has 3 kinds, respectively: nigella glandulifera Freyn (nigella glandulifera Preyn), has another name called Semen Nigellae; Fruit Nigella damascena L. (Nigella sativa), has another name called a Nigella damascena L.; And Nigella damascena L. (Nigella damascena L).The seed of nigella glandulifera Freyn is that three prismatic are avette, long 2.5-3mm, wide about 1.5mm.Surface black, coarse, top is narrower and sharp, and lower end is slightly blunt, and have irregular projection, matter is hard, section Lycoperdon polymorphum Vitt, have oiliness (boundary flora editorial board. Xinjiang flora.2nd volume, the 1st fascicle [M]. Urumchi: Xinjiang science and technology health publishing house, 1993:231.).Fruit Nigella damascena L. (sativa) is extensively distributed in Mediterranean Region (Egyptian, Pakistani etc. ground), and recording in the bright medical book of gouy has therapeutical effect to asthma and dyspnea; Nigella damascena L. (damascena) is mainly distributed in European Region; Nigella glandulifera Freyn (glandulifera) is the distinctive plant resources in Xinjiang, is Xinjiang of China Uygur nationality medicinal herbs most in use.Uygur medicine is mainly with nigella glandulifera Freyn (nigella glandulifera seeds, NGS) outward for hair growth promoting, black hair, pain relieving, antipruritic etc., take orally and be used for the treatment of flu etc., after soaking grape vinegar with Semen Nigellae, be ground into fine powder, suction intranasal (State Administration of Traditional Chinese Medicine. China's book on Chinese herbal medicine [M]. Shanghai: Shanghai science tech publishing house, 1999:364).The NGS chemical composition studied comprises: the [(Liu Yuming such as fatty acid chemistry composition, volatile chemical component, studies on alkaloid constituents, the saponins based on Caulis Hederae Sinensis and the flavonoid based on kaempferol, Yang Jun mountain grandson, Liu Qinghua. the research of the sub-chemical composition of nigella glandulifera Freyn. Chinese medicine is mixed ［ J ］ .2005,7(30) 980-982); (Ni Junjun, Wu Zhaohua, Gao Huiyuan, king's Zhe star, Wu Lijun. the chemical composition of nigella glandulifera Freyn. Shenyang pharmacy college journal ［ J ］ .2007,24(4): 215-217); (thunder learned by letter, Wang Hanqing, A Jiaike Baeyer Chinese mugwort Sa. dimension medicine nigella glandulifera Freyn seed chemical constitution study. and research and development of natural products ［ J ］. 2012,24:892-896,899)]
There is report fruit Nigella damascena L. (sativa) son to improve a small amount of in vitro study of respiratory disorders at present abroad, not yet report that NGS is to the research data of COPD effect.
Summary of the invention
The invention provides a kind of sub-volatile oil of medicine nigella glandulifera Freyn of tieing up in the application preparing treatment chronic obstructive pulmonary disease, overcome the deficiency of above-mentioned prior art, it effectively can solve and there is no the problem utilizing NGS volatile oil to improve respiratory disorders both at home and abroad at present, in the present invention, NGS volatile oil effectively can treat the chronic bronchitis that chronic obstructive pulmonary disease causes, effectively can improve the lung bronchospasm symptoms that chronic obstructive pulmonary disease causes simultaneously, stop and form pulmonary belb and emphysema.
Technical scheme of the present invention is realized by following measures: a kind of sub-volatile oil of medicine nigella glandulifera Freyn of tieing up is in the application preparing treatment chronic obstructive pulmonary disease.
Here is the further optimization and/or improvements to foregoing invention technical scheme:
Above-mentioned NGS volatile oil mass percent contains m-p-Cymene 41% to 63%, australene 8% to 14%, thymoquinone 3.5% to 5.8%.
Above-mentioned NGS volatile oil mass percent contains m-p-Cymene 61.48 %, australene 12.95 %, thymoquinone 3.7 3 %.
Above-mentioned volatile oil obtains as follows: take the dry NGS pulverized, add the water soaking that weight is NGS weight 8 doubly to 12 times, connect volatile oil extractor and condensing tube, reflux, extract, 2 is little of 6 hours, by distillate extracted with diethyl ether, then use anhydrous sodium sulfate drying, filtration, filtrate boils off ether, obtains the NGS volatile oil of fragrant pale yellow oil.
Above-mentioned reflux extracting time is 3h.
NGS volatile oil of the present invention has more stable anti-chronic inflammatory disease effect to the chronic bronchitis caused by chronic obstructive pulmonary disease, effectively can improve the lung bronchospasm symptoms that chronic obstructive pulmonary disease causes simultaneously, stop and form pulmonary belb and emphysema, its mechanism of action relates to the function suppressing pulmonary branches tracheal smooth muscle M cholinoceptor, reduce pulmonary branches tracheal tissue inflammatory cell and inflammatory cytokine, still belongs to the first time in research both at home and abroad at present.
Accompanying drawing explanation
Accompanying drawing 1 is normal rat lung tissue section (HE × 100) of the present invention.
Accompanying drawing 2 is pneumonia emphysema in rats model pathology lung tissue section (HE × 100) of the present invention.
Accompanying drawing 3 is NGS volatile oil low dose therapy group lung tissue section (HE × 100) of the present invention.
Accompanying drawing 4 is NGS volatile oil high-dose therapy group lung tissue section (HE × 100) of the present invention.
Accompanying drawing 5 is the total ions chromatogram of NGS chemical composition of volatile oil of the present invention.
Detailed description of the invention
The present invention by the restriction of following embodiment, can not determine concrete embodiment according to technical scheme of the present invention and practical situation.
Below in conjunction with embodiment and accompanying drawing, the invention will be further described:
Embodiment 1, the sub-volatile oil of this dimension medicine nigella glandulifera Freyn is in the application of preparation treatment chronic obstructive pulmonary disease.
According to actual needs, the application of the sub-volatile oil of above-mentioned dimension medicine nigella glandulifera Freyn at preparation treatment chronic obstructive pulmonary disease can be made further optimization and/or improvements:
Embodiment 2, preferred as above-described embodiment, NGS volatile oil mass percent contains m-p-Cymene 41% to 63%, australene 8% to 14%, thymoquinone 3.5% to 5.8%.
Embodiment 3, preferred as above-described embodiment, NGS volatile oil mass percent contains m-p-Cymene 61.48 %, australene 12.95 %, thymoquinone 3.7 3 %.
Embodiment 4, be with the difference of above-described embodiment, NGS volatile oil obtains as follows: take the dry NGS pulverized, add the water soaking that weight is NGS weight 8 doubly to 12 times, connect volatile oil extractor and condensing tube, reflux, extract, 2 is little of 6 hours, by distillate extracted with diethyl ether, then use anhydrous sodium sulfate drying, filtration, filtrate boils off ether, obtains the NGS volatile oil of fragrant pale yellow oil.
Embodiment 5, above-mentioned reflux extracting time is 3h.
The quality control of 1.NGS volatile oil:
1.1 extract to vapor distillation (HD) method the NGS volatile oil obtained by GC-MS condition carries out Chemical bath deposition, obtain its total ion current figure, see Fig. 5, to the mass spectrum at each peak of total ion current figure, through Nist, Wiley standard spectrum library searching and artificial spectrum unscrambling, analyze and determine each chemical composition; The percentage contents of each component is represented with areas of peak normalization method.HD method is extracted NGS volatile oil and is identified 28 kinds of compounds such as m-p-Cymene (61.48 %), australene (12.95 %), thymoquinone (3.7 3 %).
1.2 GC methods measure thymoquinone content in NGS volatile oil: at SuPelcowax-10 capillary chromatographic column (0.25 mm × 60 m, 0.25 μm), and column temperature adopts temperature programming 65 DEG C to keep 10 min, 2.2 DEG C of min
-1rise to 255 DEG C, keep 30 min, vaporizer temperature 255 DEG C; Flow 1.09 mlmin
-1, split ratio is under the GC condition of 60:1, proceeds as follows:
(1) preparation of need testing solution: precision takes NGS volatile oil 39.01 mg that HD extracts, and adds dehydrated alcohol and makes 3.901 mg.mL
-1solution, for subsequent use;
(2) preparation of reference substance solution: it is appropriate that precision takes thymoquinone reference substance, adds dehydrated alcohol and make 1.91 mg.mL
-1solution, shake up, to obtain final product;
(3) precision test: get thymoquinone reference substance solution 0.2 μ L, repeat sample introduction 3 times, the RSD=1.5 % of thymoquinone peak area, precision is good;
(4) sample tests: get reference substance solution and each 0.2 μ L sample introduction of need testing solution respectively, measure by above-mentioned condition, one point external standard method is quantitative; By measuring, the content of thymoquinone in volatile oil is 1.58 %, RSD=1.8 %.
2.NGS volatile oil pharmacological research:
The lung bronchus spasmolysis effect of 2.1 NGS volatile oil
2.1.1 mouse Histamine draws and breathes heavily experiment:
Mice is divided into matched group and administration group, matched group comprises: negative control group (i.e. normal saline group), positive controls (i.e. aminophylline group) and NGS decocting liquid group, and administration group comprises: NGS volatile oil low dose group and NGS volatile oil high dose group.
Adopt spray acecoline and histamine phosphate mixture can excited tracheal smooth muscle, cause bronchospasm, cause mice to breath with cough symptom, observe each group of impact on mice asthmatic latent period length.
Conclusion: dramamine is the current known medicine improving respiratory function, it can effectively relax bronchial smooth muscle, although NGS decocting liquid group comparatively normal saline group asthmatic latent period extends, but NGS volatile oil low dose group and NGS volatile oil high dose group, all comparatively decocting liquid group asthmatic latent period obviously extends, and illustrates that NGS volatile oil can alleviate lung bronchospasm symptoms.Experimental result is in table 1.
Table 1 NGS volatile oil on white mice relieving asthma experiment impact (
, n=10)
| Group | Dosage (mg/kg) | Incubation period (s) |
| Normal saline group | - | 81.9±4.28 |
| Aminophylline group | 100 | 150.5±7.84**▲▲ |
| Decocting liquid group | 900 | 103.2±6.34** |
| NGS volatile oil low dose group | 0.1ml/kg | 105.9±22.22** |
| NGS volatile oil high dose group | 0.4ml/kg | 138.5±38.79**▲▲ |
Note: compare * * P<0.01 with normal saline group, * P<0.05 compares ▲ ▲ P<0.01 with decocting liquid group, ▲ P<0.05, ■ ■ P<0.01 is compared, ■ P<0.05 with aminophylline group
2.1.2 Guinea pig lung perfusion experiment:
Get the Cavia porcellus 36 of body weight 400-500g, be divided into histamine model group, isoproterenol group at random, dosage group and NGS volatile oil high dose group in decocting liquid group, NGS volatile oil low dose group, NGS volatile oil; During experiment, histamine model group and isoproterenol group repeat to do 6 Cavia porcellus lung airway perfusions, and decocting liquid group repeats to do 6 Cavia porcellus lung airway perfusions; At every turn under histamine impact, NGS volatile oil repeats experiment 6 times by low middle high dose order with 6 Cavia porcelluss.According to the change of perfusion flow, the effect of assessment NGS volatile oil.
Conclusion: isoproterenol is the medicine of current known treatment bronchial asthma, although in decocting liquid and NGS volatile oil low dose group, NGS volatile oil dosage group, NGS volatile oil high dose group all comparatively histamine model group obviously increase lung airway perfusion amount, but, in NGS volatile oil low dose group, NGS volatile oil, comparatively decocting liquid group increase lung airway perfusion amount is obvious for dosage group, NGS volatile oil high dose group, and has dose-dependant trend between the low middle high dose group of NGS volatile oil.Illustrate that NGS volatile oil has bronchiectatic activity.The results are shown in Table 2.
Table 2 NGS volatile oil on the impact of Guinea pig lung perfusion experiment (
, n=6)
| Group | Dosage (mg/ml) | Perfusion flow (ml/min) |
| Minimum flow | 25 | |
| Histamine model group | 10 | 6.78±0.19 |
| Isoproterenol group | 50 | 16.30±0.69** ▲▲ |
| Decocting liquid group | 27 | 8.70±0.21* |
| NGS volatile oil low dose group | 3ul/ml | 10.08±1.07** ▲ |
| Dosage group in NGS volatile oil | 6ul/ml | 12.25±1.55** ▲▲ |
| NGS volatile oil high dose group | 12ul/ml | 14.67±1.60** ▲▲ |
Note: compare with model (normal saline) group, * *
p<0.01, *
p<0.05; Compare with decocting liquid group,
▲ ▲ p<0.01,
▲ p<0.05.
2.1.3 isolated ileum segments in guinea pigs is tested:
Get Cavia porcellus 36, head of being fiercelyed attack by Cavia porcellus is lethal, cuts open the belly rapidly, and get nearly caecum portion and be about 10cm ileum, be placed in the vessel filling cold tyrode's solution, cut off mesentery along intestinal wall, segment intestinal tube being cut into 1.5 ~ 2cm is for subsequent use.Regulating thermostatic smooth muscle groove, makes water temperature remain on (37 ± 05) DEG C.Pressure transducer is connected with BL420 biological functional system.Fetch intestinal one section, a line is respectively worn at two ends, and wherein a line is fixed on L-type breather, be placed with in the bath mortise of 20mLbotting liquid, pH value of solution=7.3, solution is water white transparency, fixed L type breather, and regulating thermostatic smooth muscle groove, slowly pass into bubble (2 bubble/s).The intestinal tube other end is connected with pressure transducer, adds 1g load, opens BL 420 biological functional system, and after intestinal tube exercise recovery is normal, record one section of intestinal tube normal activity curve, start to drip administration, dosage is with Guinea pig lung perfusion experiment.
Conclusion: atropine sulfate be the spasm of current known releasing smooth muscle medicine, compare with decocting liquid matched group, dosage group in NGS volatile oil low dose group, NGS volatile oil, NGS volatile oil high dose group all can make isolated ileum segments in guinea pigs contractive amplitude reduce obviously, and have statistics anticipate (
p<0.01), compare with atropine sulfate group, dosage group in NGS volatile oil low dose group, NGS volatile oil, NGS volatile oil high dose group can make isolated ileum segments in guinea pigs contractive amplitude reduce obviously, and have statistical significance (
p<0.01), illustrate that NGS volatile oil is by the effect of anti-M cholinoceptor, play and remove bronchial muscular spasm effect (spasmolytic effect).The results are shown in Table 3.
Impact that table 3 NGS volatile oil moves on isolated ileum segments in guinea pigs (
, n=6)
| Group | Dosage (mg/ml) | Before tension force (g) administration | After tension force (g) administration | Shrinkage amplitude reduction/g |
| Normal saline group | — | 1.24±0.03 | 1.31±0.03 | 0.07±0.02 |
| Atropine sulfate group | 2.0 | 0.92±0.01 | 0.29±0.02 | 0.62±0.02** ▲▲ |
| Decocting liquid group | 27 | 3.47±0.75 | 3.34±0.03 | 0.13±0.06 |
| NGS volatile oil low dose group | 3ul/ml | 2.40±0.65 | 1.83±0.10 | 0.58±0.08** ▲▲ |
| Dosage group in NGS volatile oil | 6ul/ml | 4.80±0.30 | 3.83±0.03 | 0.97±0.01** ▲▲■■ |
| NGS volatile oil high dose group | 12ul/ml | 2.41±0.24 | 1.06±0.03 | 1.35±0.02** ▲▲■■ |
Note: compare * * with normal saline group
p<0.01, *
p<0.05 compares with decocting liquid group
▲ ▲ p<0.01,
▲ p<0.05, compares with atropine sulfate group
■ ■ p<0.01,
■ p<0.05
The anti-chronic inflammatory disease effect of 2.2 NGS volatile oil
2.2.1 the swollen experiment of rat granuloma:
After saline rats 0.3% Nembutal sodium solution anaesthetizes (1ml/100g), abdominal part unhairing is sterilized, through abdominal incision under sterile working, by 2 aseptic cotton balls, (each cotton balls weighs 50 ± 1mg, autoclaving, respectively adds ampicillin 1mg/0.1mg/, 50 DEG C of stove-dryings) implantation rat abdomen both sides are subcutaneous respectively, skin suture immediately, for subsequent use with raising conventional after iodine liquid disinfectant.The all same modeling of other each test group.Each administration group is in operation administration next day, and continuous 7 days, within the 8th day, cervical dislocation was put to death, and takes out cotton balls, weighs, deduct the weight of raw cotton ball by this weight, be granulomatous net weight after 60 DEG C of baking boxs place 12 hours.And respectively organize difference.Calculate each group of cotton balls granulation suppression ratio, its cotton balls granulation suppression ratio (%)=(the average net weight of Normal group cotton balls granulation-average net weight of administration group cotton balls granulation)/average net weight × 100% of Normal group cotton balls granulation.During Data Processing in Experiment, cast out exceptional value to test analysis with SPSS17.0 statistical software again according to giving up commercial law (Q-method of inspection), with
represent, inspection level is α=0.05 and α=0.01.This experimental result finds that NGS volatile oil has the resist inflammation on repercussive function suppressing the weightening finish of rat granulation.Experimental result is in table 6.
Table 6 NGS extract on the swollen impact of rat granuloma (
, n=10)
| Group group | Dosage (mg/kg) | Granuloma net weight (mg) | Granulation suppression ratio (%) |
| Model (normal saline) group | - | 131．0±22.1 | |
| Aspirin group | 70 | 82.0±16.9** ▲▲ | 37.4 |
| Decocting liquid group | 650 | 106.2±16.3** | 18.9 |
| NGS volatile oil low dose group | 0.07ml/kg | 108.2±15.0** | 17.4 |
| NGS volatile oil high dose group | 0.28ml/kg | 77.1±14.1** ▲▲ | 41.1 |
Note: compare with model (normal saline) group, * *
p<0.01, *
p<0.05; Compare with decocting liquid group,
▲ ▲ p<0.01,
▲ p<0.05.
2.2.2 the histopathology of Model of Emphysema rat changes
Test and inject lipopolysaccharide and papain (Papain) and suck mediation by setting up in rat trachea and copy rat chronic inflammation and Model of Emphysema.After modeling, sub-model group, NGS volatile oil low dose group, NGS volatile oil high dose group, gastric infusion 15 days.Get left lung to fix in 10% formaldehyde, conventional dehydration, paraffin embedding, 4um thickness serial section 2, dyes for HE.Normal group bronchial mucosa epithelial cell marshalling, have no obvious cell infiltration under bronchial mucosa, cilium not damaged comes off; Alveolar structure is continuous, and alveolar wall is complete, and alveolar space without expansion, and has no and obviously oozes out; Model group bronchial mucosa epithelium degeneration necrosis comes off, there is squamous metaplasia local, goblet cell hyperplasia, tube wall muscle layer ruptures, cell infiltration (lymphocyte is main), part alveolar ectasia is merged, and alveolar space, bronchial lumen have exudate, interstitial lung cell infiltration; NGS volatile oil low dose group, NGS volatile oil high dose group comparatively model group pathological change are improved obviously, illustrate that NGS volatile oil is by reducing pulmonary branches trachea because of local inflammation, can alleviate the destruction of lung tissue.Pathological section mirror view is shown in Fig. 1, Fig. 2, Fig. 3, Fig. 4.
2.2.3 Model of Emphysema BALF of Rats inflammatory cell detects
Draw materials: after Nembutal sodium solution intraperitoneal injection of anesthesia, open thoracic cavity and isolate lung tissue, connect and prick left side bronchus, normal saline is injected right lung by main bronchus, is about 30S with have gentle hands kneading lungs, extracts irrigating solution subsequently, repeat 2 times, reclaim irrigating solution.The centrifugal rear cell sediment of irrigating solution carries out smear, and Switzerland-Giemsa staining, classifies to inflammatory cell.Model group compares with normal saline group, and aminophylline group, decocting liquid group, NGS volatile oil low dose group, NGS volatile oil high dose group all can make mononuclear phagocyte ratio reduce, and percentage of lymphocyte is increased, and have statistical significance (
p<0.01); Compare with decocting liquid matched group, aminophylline group, NGS volatile oil low dose group, NGS volatile oil high dose group all can make mononuclear phagocyte, ratio reduce, and have statistical significance (
p<0.01); Experimental result is pointed out: NGS volatile oil has the effect of reduction inflammatory cell and has antiinflammatory action.The results are shown in Table 7.
Inflammatory cell classification in table 7 each group bronchoalveolar lavage fluid in rats (
, n=7)
| Group | Dosage (mg/kg) | Inflammatory mononuclear-macrophage | Inflammatory neutrophilic granulocyte | Inflammatory lymphocytes |
| Normal saline group | — | 0.18±0.03 | 0.11±0.01 | 0.71±0.03 |
| Model group | — | 0.34±0.02 | 0.20±0.02 | 0.45±0.03 |
| Aminophylline group | 71.5 | 0.22±0.02** ▲▲ | 0.15±0.02** | 0.63±0.02** ▲▲ |
| Decocting liquid group | 650 | 0.30±0.02* | 0.18±0.01 | 0.52±0.02** |
| NGS volatile oil low dose group | 0.07ml/kg | 0.26±0.02** ▲▲ | 0.15±0.01** | 0.60±0.03** ▲▲ |
| NGS volatile oil high dose group | 0.28ml/kg | 0.21±0.01** ▲▲ | 0.15±0.01** | 0.65±0.02** ▲▲ |
Note: compare with model group, * *
p<0.01, *
p<0.05; Compare with decocting liquid group,
▲ ▲ p<0.01,
▲ p<0.05; Model group compares ， ﹟ with normal group
p<0.01
2.2.4 in bronchoalveolar lavage fluid in rats. the assay of the segmental inflammation factor TNF-α, IL-8, NF-κ B
By at irrigating solution 4 DEG C with 1500 r/min centrifugal 15 minutes, leave and take supernatant-70 DEG C freezing, standby inspection TNF-α, IL-8, NF-κ B.Model group compares with normal group, and the content of TNF-α, IL-8, NF-κ B has increase, and have statistical significance (
p<0.01).Compare with model group, aminophylline group, NGS volatile oil low dose group, NGS volatile oil high dose group all make the content of TNF-α, IL-8, NF-κ B obviously reduce, and have statistical significance (
p<0.01).Experimental result is pointed out: NGS volatile oil can make inflammatory cytokine content obviously reduce, and antiinflammatory action has been described.Experimental result is in table 8.
In table 8 bronchoalveolar lavage fluid in rats TNF-α, IL-8, NF-κ B content (
, n=7)
| Group | Dosage (mg/kg) | TNF-α(ng/ml) | IL-8(ng/ml) | NF-κB(ng/ml) |
| Normal group | — | 0.23±0.02 | 0.49±0.07 | 0.40±0.03 |
| Model group | — | 0.37±0.05﹟ | 0.98±0.05﹟ | 0.86±0.24﹟ |
| Aminophylline group | 71.5 | 0.27±0.03** | 0.59±0.06** ▲▲ | 0.52±0.13** |
| Decocting liquid group | 650 | 0.33±0.05 | 0.83±0.10* | 0.65±0.13 |
| NGS volatile oil low dose group | 0.07ml/kg | 0.29±0.03** | 0.67±0.07** | 0.59±0.18* |
| NGS volatile oil high dose group | 0.28ml/kg | 0.28±0.02** | 0.60±0.10** ▲▲ | 0.55±0.17** |
Note: compare with model (normal saline) group, * *
p<0.01, *
p<0.05; Compare with decocting liquid group,
▲ ▲ p<0.01,
▲ p<0.05; Model group compares ， ﹟ with normal group
p<0.01
2.2.5 the determination of activity of people's neutrophil elastase
Show the impact experiment of HNE, volatile oil and flavone high low dose group, non-oils and fats low dose group can reduce the activity (with model group ratio) of HNE.Illustrate that volatile oil and flavone have certain effect for the decomposition preventing neutrophil elastase to pulmonary branches tracheal wall elastic fiber.
Getting normal person and chronic obstructive disease of lung human blood, be divided into 12 groups, is Normal group, COPD matched group, aminophylline group, decocting liquid group, NGS volatile oil low dose group, NGS volatile oil high dose group.Often add each group of compound in pipe blood.Through hatching, centrifugal, get supernatant, ELLSA method measures the content of each group of neutrophil elastase.Show the impact experiment of HNE, compared with model group, NGS volatile oil low dose group, NGS volatile oil high dose group can reduce the activity of HNE.Illustrate that NGS volatile oil has certain effect for the decomposition preventing neutrophil elastase to pulmonary branches tracheal wall elastic fiber.Experimental result is in table 9.
The activity of table 9 Human neutrophil elastase (
, n=7)
| Group | Dosage (mg/ml) | HNE(ng /ml) |
| Normal controls | 0.40±0.03 | |
| COPD contrasts | 0.66±0.08 | |
| Aminophylline | 65 | 0.49±0.04** |
| Decocting liquid | 300 | 0.59±0.31 |
| NGS volatile oil low dose group | 33 | 0.55±0.07** |
| NGS volatile oil high dose group | 132 | 0.53±0.08** |
In summary, NGS volatile oil can make mononuclear phagocyte ratio in lung tissue reduce, reduce inflammatory cell infiltration, and the inflammation-inhibiting factor discharges; Stop granulomatous chronic inflammation processes; Neutrophil elastase can be prevented the decomposition of pulmonary branches tracheal wall elastic fiber, illustrate that NGS volatile oil has more stable anti-chronic inflammatory disease effect to the chronic bronchitis caused by chronic obstructive pulmonary disease, simultaneously can by blocking the effect of M cholinoceptor, effective lung bronchospasm symptoms improving chronic obstructive pulmonary disease and cause, play spasmolytic effect, thus stop formation pulmonary belb and emphysema.
3.NGS volatile oil safety evaluatio:
Because toxicity is very little, actual carry out be NGS volatile oil maximum tolerated dose experiment.By NGS volatile oil by oral capacity 0.5ml10g-1, concentration is made into corresponding solution by 1:0.5.
NGS volatile oil: 1:0.5 is made into: 20ulkg-1,40ulkg-1,80ulkg-1,160ulkg-1,320ulkg-1 are divided into five dose gradients to carry out trial test, within 48 hours, mice is all without dead.According to trial test result, get 40 kunming mices, body weight 18.0 ~ 22.0g, male and female half and half.Maximum oral capacity (0.5ml10g-1) dosage is adopted once to be 320ulkg-1, interval is administered once after 2 hours again, namely total oral dose is 640ulkg-1, little of observation in 7 days through 24, animal is without any Novel presentation, and without dead, therefore 640ulkg-1 dosage is the maximum tolerated dose of mice to NGS volatile oil.
Claims (1)
1. tie up the application of the sub-volatile oil of medicine nigella glandulifera Freyn at preparation treatment chronic obstructive pulmonary disease, wherein: this NGS volatile oil mass percent contains m-p-Cymene 61.48 %, australene 12.95 %, thymoquinone 3.73 %; This NGS volatile oil obtains as follows: take the dry NGS pulverized, add the water soaking that weight is NGS weight 8 doubly to 12 times, connect volatile oil extractor and condensing tube, reflux, extract, 2 is little of 6 hours, by distillate extracted with diethyl ether, then use anhydrous sodium sulfate drying, filtration, filtrate boils off ether, obtains the NGS volatile oil of fragrant pale yellow oil.
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| US10793307B2 (en) | 2012-07-06 | 2020-10-06 | 3-D Matrix, Ltd. | Fill-finish process for peptide solutions |
| CN103725420B (en) * | 2013-12-20 | 2016-07-13 | 江南大学 | A kind of extract the method for Nigella damascena L. platymiscium Volatile Oil from Seed, device and application |
| ES2712608T3 (en) | 2014-03-10 | 2019-05-14 | 3 D Matrix Ltd | Self-assembling peptides for the treatment of pulmonary bullae |
| EP3116551B1 (en) | 2014-03-10 | 2022-09-07 | 3-D Matrix Ltd. | Sterilization of peptide compositions |
| AU2015229549B2 (en) | 2014-03-10 | 2019-05-23 | 3-D Matrix, Ltd. | Self-assembling peptide compositions |
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| CN108057089B (en) * | 2018-02-24 | 2021-03-02 | 河南中医药大学第一附属医院 | Moxibustion powder for treating chronic obstructive pulmonary disease and preparation method and application thereof |
| CN113341048A (en) * | 2021-07-02 | 2021-09-03 | 锡林郭勒职业学院 | Quality evaluation method of nigella sativa prescription |
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