CN102091124A - Medical application of spearmint oil preparation - Google Patents
Medical application of spearmint oil preparation Download PDFInfo
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- CN102091124A CN102091124A CN 201110032801 CN201110032801A CN102091124A CN 102091124 A CN102091124 A CN 102091124A CN 201110032801 CN201110032801 CN 201110032801 CN 201110032801 A CN201110032801 A CN 201110032801A CN 102091124 A CN102091124 A CN 102091124A
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- menthae rotundifoliae
- oleum menthae
- lung tissue
- chronic obstructive
- obstructive pulmonary
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Abstract
The invention provides a medical application of spearmint oil in preparation of medicaments for treating chronic obstructive pulmonary diseases. The spearmint is taken from labiatae mentha, is obtained by vapor distillation and rectification, and mainly contains 20-60% of limonene and 20-70% of carvone. The pharmacodynamics proves that the spearmint oil provided by the invention lowers the contents of lung tissue TNF (tumor necrosis factor)-alpha and IL-1 beta for lipopolysaccharide, inhibits the over-expression of MMP-9, has an effect on improving models of Klebsiella pneumoniae infection and rat chronic obstructive pulmonary diseases caused by LPS (lipopolysaccharide), has an effect on reducing expression enhancement of lung tissue Nrf2 protein of a COPD (chronic obstructive pulmonary disease) model, and lowers the content of lung tissue IL-8 and the expression of a CCR2 receptor. The spearmint oil provided by the invention is natural and nontoxic and can be used for preparing medicaments for treating chronic obstructive pulmonary diseases.
Description
Technical field
The invention belongs to the purposes of natural plants, relate to the application of Chinese medicine Oleum Menthae Rotundifoliae in preparation treatment chronic obstructive pulmonary disease medicine.
Background technology
Herba Menthae Rotundifoliae (Mentha spicata (L.) Hudson) has another name called Mentha viridis L, Mentha spicata L. etc., and English name spearmint belongs to Labiatae (Lamiaceae) Mentha (Mentha), is perennial perennial root draft.According to " national Chinese herbal medicine compilation " record, Herba Menthae Rotundifoliae has dispelling wind, regulates the flow of vital energy the pain relieving effect.Be used for flu, cough, headache, abdominal distention, dysmenorrhea.Modern study shows that Herba Menthae Rotundifoliae water decoction, ethanol extract and volatile oil are external to animal pathogen: Salmonella gallinarum, chicken colibacillosis, Intestinum Sus domestica coccus, Staphylococcus hyicus have certain mattress effect that presses down, and it is apparent in view especially Staphylococcus hyicus to be suppressed effect.The non-essential oil component of Herba Menthae Rotundifoliae can suppress lipid peroxidation effectively, suppresses
The DNA damage that OH causes alleviates the harm to body of free radical and active oxygen.Herba Menthae Rotundifoliae has the obvious suppression effect to the local acute inflammation that Ovum Gallus domesticus album, dimethylbenzene cause.Oleum Menthae Rotundifoliae (Spearmint oil) is the volatile oil that extracts and obtain through rectification through steam distillation from the herb of labiate Mentha Herba Menthae Rotundifoliae, and Oleum Menthae Rotundifoliae is faint yellow or yellow-green liquid.Has the blue or green hay-scented gas of growing.Be mainly used in allotment toothpaste, chewing gum spice, also can be directly used in the food such as confection and cake.Oleum Menthae Rotundifoliae is not seen the report that is useful on the treatment disease.
Summary of the invention
The purpose of this invention is to provide the application of a kind of Oleum Menthae Rotundifoliae preparation in preparation treatment chronic obstructive pulmonary disease medicine.Described Herba Menthae Rotundifoliae is taken from the Labiatae Mentha, and through vapor distillation, the Oleum Menthae Rotundifoliae that obtains through rectification mainly contains limonene and carvone again.Also contain medicinal diluent in the described medicine.
Oleum Menthae Rotundifoliae provided by the invention contains 20 ~ 60% limonenes and 20 ~ 70% carvones.
Used diluent comprises ethanol, surfactant, carbohydrate and soybean oil in the Oleum Menthae Rotundifoliae provided by the invention.
Ratio is 0.1:10-10:0.1(g:g or g:ml between Oleum Menthae Rotundifoliae provided by the invention and the diluent).
Oleum Menthae Rotundifoliae provided by the invention can solid or semi-solid form administration, comprises soft capsule, soft gelatin capsule, microencapsulation and enteric coated capsule, preferred microencapsulation and soft capsule form.All right liquid form administration comprises suspensoid, Emulsion and inhalant.
The present invention has the following advantages: (1) Oleum Menthae Rotundifoliae provided by the invention be from Labiatae Mentha Herba Menthae Rotundifoliae plant, extract contain limonene and carvone.(2) Oleum Menthae Rotundifoliae provided by the invention proves through pharmacodynamics: the induced lung edema due to disorder of QI sample that Oleum Menthae Rotundifoliae causes lipopolysaccharide (LPS) changes the certain protection effect, this effect is because Oleum Menthae Rotundifoliae has reduced the content of lung tissue TNF-α and IL-1 β, has suppressed crossing of MMP-9 and has expressed; Oleum Menthae Rotundifoliae has the improvement effect to rat chronic obstructive pulmonary disease (COPD) model that klebsiella pneumoniae infects and LPS causes, COPD model lung tissue Nrf2 protein expression is strengthened the reduction effect; The rat copd model that further utilizes fumigation and LPS to cause observe Oleum Menthae Rotundifoliae to pneumonia, emphysema, goblet cell hypertrophy, collagen deposition thicken, Airway Remodeling has the improvement effect, its mechanism may be because Oleum Menthae Rotundifoliae has reduced content and the CCR2 receptor expression of lung tissue IL-8.Pharmacodynamic study shows that Oleum Menthae Rotundifoliae has therapeutical effect to chronic obstructive pulmonary disease.(3) Oleum Menthae Rotundifoliae provided by the invention can be used for treating chronic obstructive pulmonary disease.(4) Oleum Menthae Rotundifoliae Nantural non-toxic provided by the invention.
The specific embodiment
Be further described below in conjunction with embodiment.
Embodiment 1 study of pharmacy
Oleum Menthae Rotundifoliae is to extract from the herb of labiate Mentha Herba Menthae Rotundifoliae (Mentha spicata (L.) Hudson).Method is to get the Herba Menthae Rotundifoliae herb to add 6 times of water, uses vapor distillation 4h, obtains the volatile oil Aromatic water, heavily obtains crude product volatile oil after the rectification.Under normal pressure, fractional distillation, the Herba Menthae Rotundifoliae volatile oil effective site of collecting 60 ~ 80 ℃ of fractions claims Oleum Menthae Rotundifoliae.Oleum Menthae Rotundifoliae be little Huang to the oyster supernatant liquid, the characteristic perfume of Herba Menthae Rotundifoliae plant is arranged, proportion: 0.918～0.954, refraction index: 1.4850～1.4960.Analyzing its main component through gas chromatography-mass spectrum (GC-MS) is limonene (limonene) 20 ~ 60%, carvone (carvone) 20 ~ 70%, etc.
Embodiment 2 pharmacodynamic studies
Oleum Menthae Rotundifoliae to pneumonia, emphysema, goblet cell hypertrophy, the collagen deposition of the rat copd model that fumigation and LPS cause thicken, Airway Remodeling has the improvement effect, its mechanism may be because Oleum Menthae Rotundifoliae has reduced content and the CCR2 receptor expression of lung tissue IL-8, the airway resistance (R of COPD induced lung function
L) increase the reduction effect is arranged.Oleum Menthae Rotundifoliae can obviously reduce the lung tissue MDA content that klebsiella pneumoniae and LPS are caused by bacterial infection, antioxidant effect is obvious, COPD model group lung tissue of rats Nrf2 protein expression obviously strengthens, and Oleum Menthae Rotundifoliae can significantly reduce the proteic expression of Nrf2, and the Oleum Menthae Rotundifoliae treatment is used in prompting has the improvement effect to COPD.It may be the content that Oleum Menthae Rotundifoliae has reduced lung tissue TNF-α and IL-1 β that the induced lung edema due to disorder of QI sample change that Oleum Menthae Rotundifoliae causes LPS has certain protection effect, its mechanism, has suppressed crossing of MMP-9 and has expressed.These studies show that Oleum Menthae Rotundifoliae has therapeutical effect to chronic obstructive pulmonary disease.
(1) airway resistance (R of Oleum Menthae Rotundifoliae COPD induced lung function that fumigation and LPS are caused
L) influence
In the COPD rat model that fumigation and LPS cause, with methacholine (Mch) 0.5,1.0,2.0,8.0 mg mL
-1Concentration stimulates can cause model group airway resistance %(R
L%) increase, significant difference is relatively arranged with normal group
P＜0.05, at Mch 1.0 mgmL
-1Under the concentration, Oleum Menthae Rotundifoliae 300 mgkg
-1Group can make R
L% obviously descends (referring to table 1) than model group, shows that the pulmonary function airway resistance that Oleum Menthae Rotundifoliae can reduce the COPD rat increases.
Compare with the normal control group,
# P＜0.05; Compare * with model group
P＜0.05.
(2) influence of inflammatory cell number in Oleum Menthae Rotundifoliae the COPD BALF of Rats that fumigation and LPS are caused
The COPD rat that fumigation and LPS cause, total white blood cells, neutrophilic granulocyte number, lymphocyte number and mononuclear phagocyte number are than the equal showed increased of normal group in the model group bronchoalveolar lavage fluid (BALF).Compare Oleum Menthae Rotundifoliae 30,100 and 300 mgkg with model group
-1Total white blood cells, neutrophilic granulocyte number, lymphocyte number and mononuclear phagocyte number average reduce (referring to table 2) among the group BALF.Show that Oleum Menthae Rotundifoliae has the effect that suppresses inflammatory reaction among the BALF.
Visible normal group alveolar is not seen expansion under the mirror, and structure is normal, and a matter is not seen inflammatory cell infiltration, NIP cellular infiltration around the bronchus.Visible bronchiolitis and the interstitial lung inflammation in various degree of model group rat, inflammatory cell obviously soaks into, and mainly comprises lymphocyte, mononuclear phagocyte, neutrophilic granulocyte, eosinophilic granulocyte.Oleum Menthae Rotundifoliae visible bronchiolitis of each medication group and interstitial lung inflammation alleviate to some extent than model group, and inflammatory cell infiltration reduces, and lung tissue pathology inflammation degree obviously alleviates (referring to table 3).
Compare with the normal control group,
# # P＜0.01; Compare with model group,
* P＜0.05,
* P＜0.01
(u-test: if u＜1.96, then P〉0.05; If 1.96＜u＜2.58, then P＜0.05; If u〉2.58, P＜0.01 then).
(4) Oleum Menthae Rotundifoliae the sedimentary influence of COPD rat airway wall basement membrane collagen that fumigation and LPS are caused
Model group collagen deposition thickness (being area of collagen WAc/Pbm) than normal group obviously thicken (
P＜0.001), Oleum Menthae Rotundifoliae 300 mgkg
-1Group collagen deposition thickness than model group obviously reduce (
P＜0.001), shows that Oleum Menthae Rotundifoliae is to COPD rat airway wall basement membrane collagen sedimentation thickening have some improvement (referring to table 4).
Compare with the normal control group,
# # # P＜0.001; Compare * * * with model group
P＜0.001.
(5) Oleum Menthae Rotundifoliae COPD induced lung bubble structure that fumigation and LPS are caused changes and the influence of bronchioles wall thickening
The model group alveolar differs in size, the alveolar structure disorder, alveolar duct, alveolar sac and alveolar are obviously expanded, the alveolar wall attenuation, and tearing in various degree arranged, be fused into pulmonary belb, compare with normal group, the average liner of lung (Lm) at interval obviously increases, and average alveolar number (MAN) is obvious in the unit are reduces, bronchioles wall thickness/external diameter ratio obviously increases, and the bronchioles wall obviously thickens.Each medication group of Oleum Menthae Rotundifoliae and model group more all can make MAN showed increased, alveolar destroy minimizing; Bronchioles wall thickness/external diameter ratio all obviously reduces (referring to table 5), and the obvious attenuation of bronchioles wall shows that Oleum Menthae Rotundifoliae has obvious inhibitory action to the bronchioles wall thickening.Oleum Menthae Rotundifoliae can reduce the alveolar that fumigation and LPS cause to be destroyed, and has certain lungs protective effect.
Model group and normal group compare, bronchus, the obvious hypertrophy of bronchioles goblet cell; The positive % of goblet cell obviously increases.Each medication group of Oleum Menthae Rotundifoliae obviously reduces (referring to table 6) than the positive goblet cell hypertrophy of model group; The positive % of goblet cell obviously reduces.Goblet cell is relevant with the high secretion of respiratory mucus, and Oleum Menthae Rotundifoliae can suppress COPD rat airway mucus hypersecretion.
(7) Oleum Menthae Rotundifoliae COPD lung tissue of rats IL-8 content influence that fumigation and LPS are caused
Model group lung tissue of rats homogenate IL-8 content increases (P＜0.001) than matched group is obvious; Oleum Menthae Rotundifoliae 300 and 100 mgkg
-1Group all obviously reduces (P＜0.O1), show that Oleum Menthae Rotundifoliae has tangible antiinflammatory action (referring to table 7) than model group.
(8) Oleum Menthae Rotundifoliae suppresses COPD lung tissue of rats CCR2 expression
Light microscopic is observed down, and the visible a small amount of CCR2 of normal lung tissue expresses, and model group lung tissue macrophage CCR2 strong positive is expressed and is obvious pale brown color, and Herba Menthae Rotundifoliae line of oils CCR2 is weak positive expression.The gray value of CCR2 in the graphical analysis lung tissue of rats (gray, gray value is inversely proportional to expressing the pale brown color of color, referring to table 8), the result shows that model group lung tissue CCR2 expression ratio normal control group obviously increases; Each medication group lung tissue CCR2 expression ratio model group of Oleum Menthae Rotundifoliae significantly reduces.
Compare with the normal control group,
# # # P＜0.001; Compare * * with model group
P＜0.01, * * *
P＜0.001.
(9) influence of Oleum Menthae Rotundifoliae COPD lung tissue of rats MDA content that klebsiella pneumoniae and LPS are caused
Model group lung tissue of rats homogenate malonaldehyde (MDA) content increase than matched group is obvious (
P＜0.05); Each medication group lung tissue MDA content than model group all obviously reduce (
P＜0.01), shows Oleum Menthae Rotundifoliae Wheat Protein (referring to table 9).
Compare with the normal control group
# P＜0.05; Compare * with model group
P＜0.05, * *
P＜0.01.
(10) Oleum Menthae Rotundifoliae suppresses the COPD lung tissue of rats Nrf2 protein expression that klebsiella pneumoniae and LPS cause
Light microscopic is observed down, and the interior Nrf2 protein expression of bronchioles and alveolar epithelial cells is obvious pale brown color in the model group lung.Through graphical analysis, in the model group lung bronchioles Nrf2 expression ratio normal control group obviously increase (
P＜0.01); Oleum Menthae Rotundifoliae 30 ㎎ ㎏
-1The group lung in bronchioles Nrf2 expression ratio model group significantly reduce (
P＜0.05, referring to table 10).Nrf2 acts on ARE and regulates the antioxidation expression of gene, thereby the protection lungs are exempted from the influence of oxide.COPD model group lung tissue of rats Nrf2 protein expression obviously strengthens, and Oleum Menthae Rotundifoliae can significantly reduce the proteic expression of Nrf2, and the Oleum Menthae Rotundifoliae treatment is used in prompting has the improvement effect to COPD oxidation change.
(11) Oleum Menthae Rotundifoliae emphysema sample that LPS is caused changes the influence that TNF alpha, IL-1 β are expressed
TNF-α, IL-1 β content obviously increase than matched group in the homogenate of model group lung tissue of rats; Oleum Menthae Rotundifoliae 30 and 100 mgkg
-1Group can reduce the content of TNF-α and IL-1 β in the lung tissue of rats homogenate respectively, illustrates that Oleum Menthae Rotundifoliae has tangible antiinflammatory action (referring to table 11).
(12) Oleum Menthae Rotundifoliae emphysema sample that LPS is caused changes the influence that lung tissue of rats TIMP-1 content, MMP-9 are expressed
Light microscopic is observed down, and bronchial epithelial cell all has expression between each group; Visible a small amount of MMP-9 expresses in the matched group alveolar tissue, model group MMP-9 increasing expression, inflammatory cell such as macrophage, neutrophilic granulocyte strong positive are expressed and are pale brown color, and alveolar epithelial cells is weak positive expression and is yellow, and Herba Menthae Rotundifoliae line of oils MMP-9 expresses than a little less than the model group.Detect MMP-9 expression in the lung tissue of rats with Image Pro-Plus 6.0 image analysis systems, its expression values (MOD value) model group obviously increases than matched group, illustrates that LPS can cause the high expressed of lung tissue of rats MMP-9; Each administration group of Oleum Menthae Rotundifoliae can significantly reduce lung tissue of rats MMP-9 and express the MOD value, and the prompting Oleum Menthae Rotundifoliae has inhibitory action to the high expressed of the lung tissue of rats MMP-9 that LPS causes.The ELISA testing result of TIMP-1 lung tissue homogenate shows, though model group TIMP-1 content is compared with model group than the matched group not statistically significant that raises to some extent, the TIMP-1 content of each administration group of Oleum Menthae Rotundifoliae all descends to some extent, but also not statistically significant.Illustrate that LPS can cause the high expressed of lung tissue MMP-9, though the content of its natural mortifier TIMP-1 is increased to some extent, but no difference of science of statistics, pointing out repeatedly and splashing into LPS in the air flue mainly is the expression of crossing that has caused lung tissue MMP-9.Oleum Menthae Rotundifoliae is expressed crossing of lung tissue MMP-9 inhibitory action (referring to table 12).
Compare with matched group,
# # # P＜0.001; Compare * with model group
P＜0.05, * *
P＜0.01, * * *
P＜0.001.
Embodiment 3 toxicological studies
Oleum Menthae Rotundifoliae (mice, per os) LD50 is 5.714g/kg, 95% fiducial limit, 4.470～7.304g/kg; Oleum Menthae Rotundifoliae (rat, per os) LD
505000mg/kg, GRAS (FDA, § 182.20,2000).
Embodiment 4 preparations
Oleum Menthae Rotundifoliae can be through intravenous, topical, but is preferred with the oral administration, is used for the treatment of chronic obstructive pulmonary disease.This medicine is preferably with the Capsule form administration, or with liquid or semi-solid form administration.With the microcapsule is example: get Oleum Menthae Rotundifoliae and add gumwater and put emulsifying in the tissue refiner, make emulsion, with gelatin solution mixing (Oleum Menthae Rotundifoliae: arabic gum: the gelatin ratio is 1:1:1), 10% acetum is transferred pH, prepare microcapsule, make microcapsule through curing, then microcapsule is dressed up hard capsule, every capsule contains Oleum Menthae Rotundifoliae 30 ~ 60mg, optimised quantity 50mg, day dosing 3 ~ 6mgkg
-1Body weight.With the soft capsule is example: with gelatin, glycerol, water is the capsule material, ethyl hydroxybenzoate is as antiseptic, in Oleum Menthae Rotundifoliae, add diluent (soybean oil), the proportioning of Oleum Menthae Rotundifoliae and diluent is 1:5 to 5:1, the optimum ratio Oleum Menthae Rotundifoliae: soybean oil is 1:1(g:g), each capsule includes Oleum Menthae Rotundifoliae 50 ~ 200mg, optimised quantity 100mg, day dosing 3 ~ 6mgkg
-1Body weight.(if Oleum Menthae Rotundifoliae: liquid diluent then is g:ml).
Oleum Menthae Rotundifoliae can also be equipped with the mixture of ethanol, surfactant, carbohydrate or these materials, is prepared into suspensoid or Emulsion.Its amount that contains Oleum Menthae Rotundifoliae is by weight 0.5 ~ 10%, and is best 1 ~ 2%, and the every ml of suspensoid contains Oleum Menthae Rotundifoliae 10mg, each 10ml, day dosing 30ml.Emulsion, every 100ml contains 300mg, intravenous injection 100ml, every day 1 time.The every ml of inhalant contains 10mg, and atomizing sucks.
Claims (3)
1. the application of Oleum Menthae Rotundifoliae preparation in preparation treatment chronic obstructive pulmonary disease medicine, described Herba Menthae Rotundifoliae is taken from the Labiatae Mentha, through vapor distillation, the Oleum Menthae Rotundifoliae that obtains through rectification again, mainly contain limonene and carvone, also have medicinal diluent in the described preparation, ratio is 0.1:10-10:0.1 between Oleum Menthae Rotundifoliae and the diluent.
2. the application of a kind of Oleum Menthae Rotundifoliae according to claim 1 in preparation treatment chronic obstructive pulmonary disease medicine is characterized in that it is 20 ~ 60% limonenes and 20 ~ 70% carvones that described Oleum Menthae Rotundifoliae contains main active.
3. the application of a kind of Oleum Menthae Rotundifoliae according to claim 1 in preparation treatment chronic obstructive pulmonary disease medicine is characterized in that the dosage form of described medicine is solid, semisolid or liquid preparation.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105052990A (en) * | 2015-08-06 | 2015-11-18 | 华南师范大学 | Application of insect transcription factor in pest control |
| CN109380218A (en) * | 2018-11-22 | 2019-02-26 | 信阳农林学院 | One ESSENTIAL OIL sustained-release core agent and its application |
-
2011
- 2011-01-30 CN CN 201110032801 patent/CN102091124A/en active Pending
Non-Patent Citations (3)
| Title |
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| 《中国药学杂志》 20100331 夏锦芳 等 留兰香油对慢性阻塞性肺疾病大鼠的气道炎症反应与白细胞介素-8和CCR2受体表达的影响 423-428 第45卷, 第6期 2 * |
| 《信阳师范学院学报（自然科学版）》 20021031 魏金凤等 留兰香油提取方法的探讨 第15卷, 第4期 2 * |
| 《浙江大学学报(医学版)》 20080725 赵春贞等 留兰香油对大鼠慢性阻塞性肺疾病模型肺组织炎症氧化改变和Nrf2蛋白表达的影响 357-362 第37卷, 第04期 2 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105052990A (en) * | 2015-08-06 | 2015-11-18 | 华南师范大学 | Application of insect transcription factor in pest control |
| CN105052990B (en) * | 2015-08-06 | 2017-07-25 | 华南师范大学 | A kind of application of insect transcription factor in control of insect |
| CN109380218A (en) * | 2018-11-22 | 2019-02-26 | 信阳农林学院 | One ESSENTIAL OIL sustained-release core agent and its application |
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Application publication date: 20110615 |