CN1442197A - New use of agastache rugosus oil - Google Patents

New use of agastache rugosus oil Download PDF

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CN1442197A
CN1442197A CN 03121145 CN03121145A CN1442197A CN 1442197 A CN1442197 A CN 1442197A CN 03121145 CN03121145 CN 03121145 CN 03121145 A CN03121145 A CN 03121145A CN 1442197 A CN1442197 A CN 1442197A
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herba pogostemonis
oil
medicine
purposes
application
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CN1212146C (en
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邢东明
杜力军
丁怡
王雪莉
王伟
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Tsinghua University
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Abstract

A novel application of agastache oil in preparing the medicines for treating angiospasm, headache, hemicrania, cerebral ischemia, vascular neuropsychic disfunction, cerebral fatigue, and myocardial ischemia is disclosed. Agastache oil can increase brain blood flow and NO content of experiment animal.

Description

The new purposes of oil of Herba Pogostemonis
Technical field
The present invention relates to the new pharmaceutical applications of oil of Herba Pogostemonis, is the application of oil of Herba Pogostemonis in preparation treatment cerebrovascular medicine specifically, and the application of oil of Herba Pogostemonis in the caused multiple disease medicament of preparation treatment vasospasm.
Background technology
Herba Pogostemonis is the dry aerial parts of Labiatae thorn stamen grass platymiscium Herba Pogostemonis Pogostemon cablin (Blanco) Benth. or Herba Pogostemonis platymiscium Herba Pogostemonis Agastache rugosa (Fisch.et Mey.) Kuntze, with all herbal medicine.Herba Pogostemonis is divided into Stone steles Herba Pogostemonis and Hainan Herba Pogostemonis again, in China Taiwan, and Guangdong, all there is cultivation on ground such as Hainan and Yunnan.Herba Pogostemonis is called herba agastachis rugosae, Lysimachia capillipes Hemsl, Herba microtoenae insuavis again.All there is distribution each province, China north and south.The Herba Pogostemonis main component has Herba Pogostemonis alcohol (patchoulialcohol), Herba Pogostemonis ketone (pogostone), anisaldehyde (anisaldehyde) etc.
Herba Pogostemonis is used for the treatment of the history in existing more than 2000 year of disease, but is mainly used in the disease of treatment digestive system, as vomiting, and diarrhoea, flu, degradation under the appetite.Have eliminating turbid pathogen with aromatics, the appetizing preventing or arresting vomiting is delivered the effect (Pharmacopoeia of the People's Republic of China version in 2000) of expelling summer-heat." medicine justice) " record " Herba Pogostemonis, its gas fragrance, the benefaction gastric qi, in transferring with this, stopping vomiting is told cholera.And perfume can and close the five internal organs, if incoordination between the spleen and stomach helps stomach and advances diet with it, the merit of the appetizing of being amusing is arranged ".Herba Pogostemonis " is controlled taste and tells contraryly, be the medicine of wanting most " in " Bencao Tujing " record." book on Chinese herbal medicine is new again " record Herba Pogostemonis " inducing diaphoresis to expel pathogens, dampness removing removes wind, relieves heat and thirst ".
Although Herba Pogostemonis is as medicinal with a long history, but do not appear in the newspapers Herba Pogostemonis or oil of Herba Pogostemonis and main component Herba Pogostemonis alcohol thereof, Herba Pogostemonis ketone treatment cerebral vasospasm, and the caused headache of vasospasm, migraine, cerebral ischemia, dementia, brain fag, cerebral anoxia, coronary vasospasm, the effect of diseases such as deficiency myocardial blood supply.
In years of researches, the inventor has found that oil of Herba Pogostemonis has expansion of cerebral vascular, improves angiospastic effect, can be used for treating because the cerebral vasospasm due to the vasoconstriction obstacle, headache, migraine, cerebral ischemia, vascular dementia, brain fag, cerebral anoxia, coronary vasospasm, diseases such as deficiency myocardial blood supply have been found some new reliable purposes of oil of Herba Pogostemonis.
Summary of the invention
The new purposes that the purpose of this invention is to provide oil of Herba Pogostemonis.
Oil of Herba Pogostemonis provided by the invention is the application in the medicine of the disease for preparing treatment vasospasm and cause thus.
Specifically, oil of Herba Pogostemonis of the present invention is the application in the medicine of preparation treatment headache; It is the application in the migrainous medicine of preparation treatment; It is the application in the medicine of preparation treatment cerebral ischemia; It is the application in the medicine of preparation treatment angioneurotic disorder; It is the application in the medicine of preparation treatment cerebral anoxia fatigue; It is the application in the medicine of preparation treatment deficiency myocardial blood supply.
When treatment vasospasm and the disease that causes thus thereof, be active component with the oil of Herba Pogostemonis, with the preparation process of routine, use separately or prepare the medicine of operable various different dosage forms clinically with other drug.As nasal drop, eye drop, and other department of eye medicament, powder, pill, capsule, tablet, microcapsule, soft capsule, membrane, suppository, injection, unguentum, tincture, powder, electuary, aerosol and various external preparation etc.
Experimental result of the present invention shows, the effect that oil of Herba Pogostemonis is significantly increased mice meninges blood flow.Generally after administration, promptly there was cerebral blood flow to raise in 1 minute, and shows certain dose-effect relationship.As comparing with matched group after heavy dose of (25mg/kg) administration, can make the meninges blood flow increase 15-20%.Show that oil of Herba Pogostemonis has directly dilating effect to cerebrovascular, mitigation is preferably arranged for the caused disease of vascular spasm.The effect that mouse brain cortex nitric oxide (NO) content was significantly increased in 5 minutes after the oil of Herba Pogostemonis administration.The result of this phenomenon and mice meninges blood flow has certain goodness of fit.Because NO has certain inhibitory action to the contraction of vascular smooth muscle, the energy blood vessel dilating suppresses the vascular smooth muscle spasm, so oil of Herba Pogostemonis has preferably for the caused disease of vascular spasm.In vitro tests is the result show, oil of Herba Pogostemonis has and suppresses the accumulative effect of ADP induced platelet strongly, and minimal effective concentration is 3.31 * 10 -6G/ml directly causes coagulation process aggravation and thrombosis because hematoblastic gathering improves, so this experimental result prompting oil of Herba Pogostemonis has certain anticoagulation or suppresses thrombotic effect.
The specific embodiment
When preparation has the medicine of above-mentioned new purposes, earlier Herba Pogostemonis is extracted with conventional method, the extract oil of Herba Pogostemonis with Herba Pogostemonis is an active component then.The oil of Herba Pogostemonis main component has Herba Pogostemonis alcohol (patchouli alcohol), Herba Pogostemonis ketone (pogostone), anisaldehyde (anisaldehyde) etc.
Here said extraction to Herba Pogostemonis can be the water distillation with Herba Pogostemonis, as volatile oil, and Aromatic water.Also can be with the extraction under different conditions of ethanol or other organic solvent to oil of Herba Pogostemonis.Also can be under different condition, with of the extraction of different equipment to oil of Herba Pogostemonis.Also comprise extraction with Herba Pogostemonis medical material and the mixed volatile oil of other medical material.
Be exactly individually or add that the preparation process with routine is prepared into medicament in the compound recipe on medicament is used with oil of Herba Pogostemonis.Its medicament can be the various different dosage forms that can use clinically.
Following drug study data is confirmed the new purposes of the said oil of Herba Pogostemonis of the present invention.
Zoopery example 1: to the effect of mice meninges blood flow
Observe the effect of oil of Herba Pogostemonis of the present invention to mice meninges blood flow.Oil of Herba Pogostemonis, lot number: 990418.Time spent is mixed with desired concn with normal saline.Experimental animal is a male mice in kunming, non-inbred line closed colony, and body weight 18-22g, the quality certification number: the moving word 01-3001 of doctor is provided by Chinese Academy of Medical Sciences's Experimental Animal Center.20-22 ℃ of laboratory room temperature, relative humidity 40%~60%, the ventilation fan ventilation, lamp 12h/ day, raise in cages, 8 in every cage, per three days cleaning cage houses are once.
After getting mice urethane (1.0g/kg) anesthesia, fixing head cuts skin, in the motor area of cerebral cortex (AP -1, L 2) settle laser probe (JI-200 laser microcirculation instrument, Tianjin Nankai University produces), treat stablize after 5-10 minute and begin to test cerebral blood flow, the variation of record administration front and back meninges blood flow.
This experimental observation index and index are expressed: measured result is directly through the JI-200 software processes, and the meninges blood flow is with KHz (KHz) expression, and the meninges blood flow increases percentage value [blood flow before=(the preceding blood flow of blood flow-administration after the administration)/administration].
This test dosage is respectively 25mg/kg, 12.5mg/kg and 6.25mg/kg; Route of administration is the tail intravenously administrable; The administration volume is the 0.05ml/10g mice.
This test blank is the equal-volume normal saline, and the positive drug contrast is ligustrazine injection, 40mg/2ml.Yongkang, Beijing pharmaceutical factory produces, lot number: 9811191, and the accurate word (1996) of medicine is defended No. 157008 in the capital, and the mice consumption is 25mg/kg.
This test data is all with the Excel software processes.
Table 1 oil of Herba Pogostemonis is to the effect of normal rat brain blood flow (the grouping dosage cerebral blood flow (KHz) of x ± s)
(mg/kg) 0135 10 15 (minute) matched group 31.32 ± 31.67 ± 31.59 ± 31.45 ± 31.51 ± 31.53 ±
2.71 2.02 2.58 2.69 2.63 2.27 ligustrazine 25 30.91 ± 32.66 ± 33.52 ± 33.96 ± 33.32 ± 33.2 ±
2.24 2.69 1.84 1.69*, 1.99 1.95 oil of Herba Pogostemonis 25 31.02 ± 35.44 ± 37.02 ± 37.48 ± 37.38 ± 36.91 ±
2.51 4.67 5.13* 4.08* 3.14*, 3.02 oil of Herba Pogostemonis 12.5 31.64 ± 34.14 ± 37.44 ± 37.46 ± 36.55 ± 36.32 ±
3.39 3.73 1.98* 2.46*, 2.41 1.77 oil of Herba Pogostemonis 6.25 33.73 ± 35.31 38.05 38.45 38.4 36.87
10.25 ±9.79 ±9.95 ±9.10* 6±9.51 ±9.49
With compare P<0.05 with the time matched group.n=8
Table 2 oil of Herba Pogostemonis increases percent value to normal rat brain blood flow, and (x ± s) grouping dosage cerebral blood flow increases percent value (%)
(mg/kg) 0135 10 15 (minute) matched group 0 1.45 ± 0.96 ± 0.45 ± 0.65 ± 0.78 ±
6.04 2.95 3.00 3.07 1.73 ligustrazine 25 0 5.75 ± 8.64 ± 10.08 ± 7.93 ± 7.56 ±
2.67 4.20* 4.41* 3.22* 3.89* oil of Herba Pogostemonis 25 0 14.16 ± 19.34 ± 20.96 ± 20.61 ± 19.09 ±
10.53* 12.78** 10.04** 5.42** 5.56** oil of Herba Pogostemonis 12.5 0 7.98 ± 19.35 ± 19.09 ± 16.12 ± 15.61 ±
4.80* 12.38* 8.95** 7.40* 9.36* oil of Herba Pogostemonis 6.25 0 5.31 ± 13.74 ± 15.48 ± 15.18 ± 10.28 ±
4.74 4.76* 7.36** 6.98 5.61*
With compare * P<0.05, * * P<0.01 with the time matched group.n=8
Experimental result shows, the effect that oil of Herba Pogostemonis is significantly increased mice meninges blood flow.Generally after administration, promptly there was cerebral blood flow to raise in 1 minute, and shows certain dose-effect relationship; Show that oil of Herba Pogostemonis has directly dilating effect to cerebrovascular, mitigation is preferably arranged for the caused disease of vascular spasm.
Zoopery example 2: to the effect of NO in the mouse brain (nitric oxide) content
Observe the effect of oil of Herba Pogostemonis of the present invention to NO content in the mouse brain.The used oil of Herba Pogostemonis of the present invention, lot number: 990418.Time spent is mixed with desired concn with normal saline.Experimental animal is a male mice in kunming, non-inbred line closed colony, body weight 18-22g; The quality certification number: the moving word 01-3001 of doctor is provided by Chinese Academy of Medical Sciences's Experimental Animal Center.20-22 ℃ of laboratory room temperature, relative humidity 40%~60%, the ventilation fan ventilation, lamp 12h/ day, raise in cages, 8 in every cage, per three days cleaning cage houses are once.
Get mice and be divided into 5 groups at random, 8 every group, the tail vein is given and different pharmaceutical.Took off neck execution mice in 5 minutes after the administration, take out full brain rapidly, separate the cerebral cortex part, drop in the liquid nitrogen fixing rapidly.Change-70 ℃ of refrigerators then over to and preserve, survey NO fully.Get mouse brain cortex during test, add the normal saline ice-water bath and be prepared into 20% homogenate (w/v), 12000 rev/mins centrifugal 30 minutes, get supernatant 0.3ml, add 1 * 10 respectively -6The quinine sulfate of mol/L (available from Sigma company) liquid 3ml, mixing.Add 1mol/L HCl 0.1ml again, 1.6 * 10 -2Mol/L N-acetylcystein (available from Sigma company) 0.3ml shakes up the back in test of 850 spectrofluorophotometers and record fluorescence intensity (excitation wavelength is 334nm, and emission wavelength is 445nm).
This test NO method of testing is the quinine sulfate method, and cerebral tissue protein quantification method is a biuret method.
Observation index and index are expressed: fluorescent value (f)/g albumen.
Measured result is through the Excel software processes.
This test dosage is respectively 25mg/kg, 12.5mg/kg and 6.25mg/kg; Route of administration is the tail intravenously administrable; The administration volume is the 0.05ml/10g mice.
This test blank is the equal-volume normal saline, and the positive drug contrast is ligustrazine injection, 40mg/2ml.Yongkang, Beijing pharmaceutical factory produces, lot number: 9811191.The accurate word (1996) of medicine is defended No. 157008 in the capital, and the mice consumption is 25mg/kg.
Table 3 oil of Herba Pogostemonis is to the influence of mouse brain cortex NO content (x ± s)
Grouping dosage (mg/kg) NO (f/g albumen)
Normal saline 3.94 ± 1.38
Ligustrazine 25 5.81 ± 2.01*
Oil of Herba Pogostemonis 25 8.98 ± 3.04**
Oil of Herba Pogostemonis 12.5 7.27 ± 2.58**
Oil of Herba Pogostemonis 6.25 6.45 ± 2.83**
Compare * P<0.05, * * P<0.01 with the normal saline group.n=8
Experimental result shows, the effect that mouse brain cortex NO content was significantly increased in 5 minutes after the oil of Herba Pogostemonis administration. the result of this phenomenon and mice meninges blood flow has certain goodness of fit.Because NO shrinks vascular smooth muscle certain inhibitory action is arranged, the energy blood vessel dilating suppresses the vascular smooth muscle spasm.So this experiment shows that oil of Herba Pogostemonis has mitigation preferably for the caused disease of vascular spasm.
Zoopery example 3: to the inhibitory action of rat platelet aggregation
Observe the inhibitory action of oil of Herba Pogostemonis of the present invention to rat platelet aggregation.The used oil of Herba Pogostemonis of the present invention, lot number: 990418.Time spent is mixed with desired concn with normal saline.Testing used animal is secondary Wistar rat, male and female half and half, and non-inbred line closed colony, moving word (95) 01-3008 of doctor, Institute of Experimental Animals, Chinese Academy of Medical Sciences provides, and body weight is 230-260g.20-22 ℃ of laboratory room temperature, relative humidity 40%~60%, the ventilation fan ventilation, lamp 12h/ day, raise in cages, 5 in every cage, per three days cleaning cage houses are once.
Get rat 10% urethane (1g/kg) anesthesia, ventral aorta blood sampling (3.8% sodium citrate anticoagulant), per minute 1000 leaves heart 3-5 minute, separate and be rich in platelet blood plasma, get and be rich in platelet blood plasma 0.15ml, put in the colorimetric pool of B1202 platelet aggregation instrument (production of Beijing biochemical instrument factory), add the oil of Herba Pogostemonis 20ul of variable concentrations respectively, 1mmol/L ADP (platelet aggregation derivant, Sigma product) 20ul.Observe and write down the maximum numerical value that changes of light absorption value in 5 minutes, with reflection platelet aggregation degree.Each concentration is made 3 parallel pipes.
This experimental observation index and index are expressed: measured result is directly through the B1202 software processes, and the platelet aggregation degree is represented with the platelet aggregation percentage rate.
This test oil of Herba Pogostemonis administration final concentration is respectively 3.31 * 10 -6G/ml, 3.31 * 10 -5G/ml, 3.31 * 10 -4G/ml, 3.31 * 10 -3G/ml, 3.31 * 10 -2G/ml.
This test is an experiment in vitro.This test blank is the equal-volume normal saline. the positive drug contrast is ligustrazine injection, 40mg/2ml.Yongkang, Beijing pharmaceutical factory produces, lot number: 9811191, and the accurate word (1996) of medicine is defended No. 157008 in the capital.The ligustrazine final concentration is 3.31 * 10 -2G/ml.
This test data is all with the Excel software processes.
The external influence to ADP induced platelet aggregation of table 4 oil of Herba Pogostemonis (x ± s)
Grouping medicine final concentration platelet aggregation percentage rate
(g/ml) (%)
Normal saline 70.11 ± 2.06
Ligustrazine 3.31 * 10 -227.26 ± 3.66**
Oil of Herba Pogostemonis 3.31 * 10 -231.26 ± 2.70**
Oil of Herba Pogostemonis 3.31 * 10 -337.92 ± 2.53**
Oil of Herba Pogostemonis 3.31 * 10 -445.68 ± 2.53**
Oil of Herba Pogostemonis 3.31 * 10 -557.33 ± 4.08*
Oil of Herba Pogostemonis 3.31 * 10 -662.49 ± 2.07*
Compare * P<0.05, * * P<0.01 with the normal saline group.n=3
This experimental result shows, oil of Herba Pogostemonis is external to be had and suppress the accumulative effect of ADP induced platelet strongly, and minimal effective concentration is 3.31 * 10 -6G/ml, the prompting oil of Herba Pogostemonis has certain anticoagulation or suppresses thrombotic effect.

Claims (9)

1. the purposes of oil of Herba Pogostemonis in the medicine of preparation treatment vasospasm and the disease that causes thus thereof.
2. according to the purposes of the described oil of Herba Pogostemonis of claim 1, it is characterized in that: described purposes is the application in the medicine of preparation treatment headache.
3. according to the purposes of the described oil of Herba Pogostemonis of claim 1, it is characterized in that: described purposes is the application in the migrainous medicine of preparation treatment.
4. according to the purposes of the described oil of Herba Pogostemonis of claim 1, it is characterized in that: described purposes is the application in the medicine of preparation treatment cerebral ischemia.
5. according to the purposes of the described oil of Herba Pogostemonis of claim 1, it is characterized in that: described purposes is the application in the medicine of preparation treatment angioneurotic disorder.
6. according to the purposes of the described oil of Herba Pogostemonis of claim 1, it is characterized in that: described purposes is the application in the medicine of preparation treatment cerebral anoxia fatigue.
7. according to the purposes of the described oil of Herba Pogostemonis of claim 1, it is characterized in that: described purposes is the application in the medicine of preparation treatment deficiency myocardial blood supply.
8. with the oil of Herba Pogostemonis medicine of active component treatment vasospasm and the disease that causes thus thereof.
9. according to the described medicine of claim 8, it is characterized in that: described medicine is with the preparation of the preparation process of routine, operable clinically various different dosage forms.
CN 03121145 2003-03-28 2003-03-28 New use of agastache rugosus oil Expired - Fee Related CN1212146C (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110201177A (en) * 2019-06-18 2019-09-06 中国人民解放军总医院第八医学中心 A kind of medical composition and its use preventing and treating coronary heart disease

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110201177A (en) * 2019-06-18 2019-09-06 中国人民解放军总医院第八医学中心 A kind of medical composition and its use preventing and treating coronary heart disease
CN110201177B (en) * 2019-06-18 2020-05-19 中国人民解放军总医院第八医学中心 Pharmaceutical composition for preventing and treating coronary heart disease and application thereof

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