CN1150930C - Cinnamon twig decoction extract for preventing and curing hypertension - Google Patents
Cinnamon twig decoction extract for preventing and curing hypertensionInfo
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- CN1150930C CN1150930C CNB011366982A CN01136698A CN1150930C CN 1150930 C CN1150930 C CN 1150930C CN B011366982 A CNB011366982 A CN B011366982A CN 01136698 A CN01136698 A CN 01136698A CN 1150930 C CN1150930 C CN 1150930C
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- extract
- cinnamon twig
- twig decoction
- butyl alcohol
- alcohol
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Abstract
The present invention relates to a cinnamon twig decoction extract for preventing and curing hypertension. The cinnamon twig decoction is stemmed from On Cold Damage of Han dynasty, is a head prescription of Zhang Zhongjing, and is a represent prescription for treating superficies deficiency syndrome of wind-stroke syndrome of taiyang channel. The cinnamon twig decoction extract is prepared from the raw materials of cassia twig, red peony root, ginger, prepared licorice root and Chinese date. After the raw materials of the cinnamon twig decoction are extracted with water and precipitated with alcohol, the alcohol-dissolved part is recovered, and the residue is extracted with n-butanal to obtain an n-butyl alcohol extract. As indicated by analysis results of two different moving phases of high-pressure liquid phase, the n-butyl part contains ingredients of paeoniflorin, etc. As indicated by pharmacological experiment research, the n-butyl part has the obvious effect of reducing blood pressure of spontaneous hypertension rat (SHR). The cinnamon twig decoction extract is a fine compound traditional Chinese medicinal preparation, and can be used as a patent medicine for oral administration. The cinnamon twig decoction extract has the advantages of convenient use, high stability, sure therapeutic effect and little toxic and side effect.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition of preventing and treating vascular hypertension, particularly a kind of is the control hypertension drug that raw material is produced with the vegetable Chinese herbal medicine.
Background technology
Guizhi decoction comes from the Han dynasty treatise on Febrile Diseases, is the chief of Zhang Zhongjing group side, is the representative side that controls the wind syndrome of TAI YANG exterior deficiency syndrome, act as mainly that expelling pathogenic factors from muscles is delivered, harmonizing yingfen and weifen.We are made up of Ramulus Cinnamomi, Radix Paeoniae Rubra, Rhizoma Zingiberis Recens, Radix Glycyrrhizae Preparata and Fructus Jujubae.The ancient Chinese medicine doctor experience is thought, no matter the guizhi decoction diseases caused by exogenous pathogenic factor, or internal injury, all debates accurately all can be applied flexibly.Empty Mr. Gu of chapter compile notes " blow and shout to waken one from error of doctor's door. two collection. the Treatise on Febrile Diseases original intention " in record: " this side legislation, from taste with Da Yingwei, week row all over the body; melt the exterior and the interior, regulate yin-yang, and QI and blood; qualcomm meridian, non-sending an expedition against, non-subsidy; and can make the person of stopping up logical; contrary person is suitable, and the person puts down partially, lattice person and; internal injury diseases caused by exogenous pathogenic factor no matter hereat all can follow the example of to control it ".
About the research of guizhi decoction effective site, relevant reported in literature guizhi decoction A partly have body temperature dual regulation [Chinese experimental pharmacology of Chinese medical formulae magazine .1998,4 (2) 11-23,25-28; 1998,4 (3) 14-16; 1999,5 (1) 33-36; CHINA JOURNAL OF CHINESE MATERIA MEDICA .2000,25 (10) 619-621]; Methanolic extract in the root of Chinese medicine Peucedanum praeruptorum DUNN and n-butanol extract, intravenous injection can both increase the anesthetized cat CBSF, causes that blood pressure reduces [the journal .1988 of Chinese Medical Sciences University, 17 (4) 255-258]; The intravenous injection of Cortex Ilicis Rotundae n-butanol extract, normal rat and folder are closed the common carotid artery rat of boosting all remarkable hypotensive effect [Chinese crude drug .1997,20 (8) 406-408]; We have reported that guizhi decoction A part and E part obviously reduce the spontaneous hypertensive rat blood pressure recently, and B part obviously rising FUFANG JIANGYA PIAN causes hypotension rat blood pressure [Chinese experimental pharmacology of Chinese medical formulae magazine .2001,7 (4) 20-23].To content of the present invention, guizhi decoction n-butyl alcohol part obviously reduces the effect of spontaneous hypertensive rat blood pressure, looks into newly through books Institute of Social Science Information of China Academy of TCM, does not appear in the newspapers)
Summary of the invention
Purpose of the present invention: being to provide a kind of Ramulus Cinnamomi extract that is used to prevent and treat vascular hypertension, is the meticulous compound preparation that raw material is produced with the Chinese herbal medicine particularly, is used to prevent and treat vascular hypertension.It is oral that it can be used as patent medicine, easy to use, its better stability of preparation, and curative effect is sure, and toxic and side effects is little.
Medicine of the present invention is made like this:
By following weight ratio configuration, 1 part of Ramulus Cinnamomi Tangyuan County side Ramulus Cinnamomi, Radix Paeoniae Rubra 0.9-1.1 part, Fructus Jujubae 0.9-1.1 part, Rhizoma Zingiberis Recens 0.9-1.1 part, Radix Glycyrrhizae Preparata 0.6-0.8 part Chinese medicine of the five flavours are formed.
Distilled water is doubly measured by weight adding 8-10 for the first time by Ramulus Cinnamomi Tangyuan County side, and post-heating extracted in water logging 30-40 minute, and 100 ℃ were boiled 30 minutes, filtration residue adds 7-9 times of water gaging again, heated and boiled 30 minutes is filtered and is discarded residue, merges twice filtrate and is recycled into extractum; Extractum adds 3 times of amount 70% ethanol, and through 16-24 hour precipitation, decompress filter discarded residue; Alcohol is molten partially recycled, again with n-butanol extraction 5-8 time, each 2-3 hour, reclaim solvent, brownish black n-butyl alcohol extractum.
Description of drawings
Fig. 1 is a guizhi decoction n-butyl alcohol part finger printing 1
Fig. 2 is a guizhi decoction n-butyl alcohol part finger printing 2
This (uv-486) chromatograph of liquid of water, C
18Post, 250 * 4.6mm, mobile phase: methanol-water (40: 60), flow velocity: 0.5ml/min detects wavelength 230nm, analyzes compositions such as peoniflorin.See Fig. 1.
This (uv-486) chromatograph of liquid of water, C
18Post, 250 * 4.6mm, mobile phase: CH
3CN-3%HOAC (H
2O) (47: 53), the flow velocity elution program of employing linear gradient: 0.8ml/min, 1ml/min (3min), 1.2ml/min (6min), 1.4ml/min (9min), 0.8ml/15min.Analyze compositions such as peoniflorin.See Fig. 2
Pharmacological evaluation proves: after Ramulus Cinnamomi Tangyuan County side or branch are carried, by above-mentioned prepared, get n-butanol extract respectively, award spontaneous hypertensive rat (SHR) mouth and raised administration 15 days, all can obviously reduce the blood pressure of SHR, and the heart rate of SHR is not had obvious influence.Experimental result sees Table 1,2,3,4.
The upright butanol extract in table 1 Ramulus Cinnamomi Tangyuan County is to the influence of SHR pressure value
(n=10)
Pressure value (X ± SD mmHg)
Group
Not
After the treatment
Treat preceding 5 days 10 days 15 days
WKY 118.0±6 110.8±2.3 114.9±2.9 116.4±4.8
SHR .9 142.4±5 159.6±4.4 176.3±7.1
### 186.5±2.9
###
.1
ΔΔΔ ###ΔΔΔ ΔΔΔ ΔΔΔ
Treatment 144.7 ± 4 151.0 ± 8.2
*160.6 ± 5.4 174.7 ± 2.5
Group SHR .9
* * ### * * ###
WKY:Wistar capital of a country kind rat
SHR: spontaneous hypertensive rat
Treatment group: guizhi decoction n-butanol extract
Compare with SHR
*P<0.05
* *P<0.05
Compare Δ Δ Δ P<0.001 with WKY
With preceding relatively ###P<0.001 of treatment
The upright butanol extract in table 2 Ramulus Cinnamomi Tangyuan County is to the influence of SHR blood pressure difference
(n=10)
Blood pressure difference (X ± SD mmHg)
Group
5 days 10 days 15 days
WKY -7.2±5.7 -3.1±7.7 -1.6±10.5
SHR 17.2±3.9
ΔΔΔ 33.8±5.7
ΔΔΔ 44.0±5.4
ΔΔΔ
Treatment group 6.3 ± 5.7
* *15.9 ± 9.3
* *30.0 ± 3.9
* *
SHR
Compare with SHR
* *P<0.001
Compare Δ Δ Δ P<0.001 with WKY
Table 1 pressure value, table 2 blood pressure difference t inspection statistics is the result show: the upright butanol extract in Ramulus Cinnamomi Tangyuan County has the effect of obvious reduction spontaneous hypertensive rat (SHR) blood pressure.
Table 3 guizhi decoction branch is proposed the influence of n-butanol extract to the SHR pressure value
(n=10)
Pressure value (X ± SD mmHg)
Group
After Zhi Liao not treating
Preceding 5 days 10 days 15 days
WKY 112.0±2.5 110.6±3.6 113.5±3.6 113.7±7.9
SHR 141.7±10. 152.4±5.4
# 165.2±7.6 171.2±6.8
###
4
ΔΔΔ ΔΔΔ ###ΔΔΔ ΔΔΔ
Treatment 139.6 ± 9.7 145.7 ± 8.2
*149.5 ± 15.2 149.9 ± 8.2
#
Group SHR
* * *
Compare with SHR
*P<0.05
* *P<0.05
Compare Δ Δ Δ P<0.001 with WKY
With preceding relatively #P<0.05 ###P<0.001 of treatment
Table 4 guizhi decoction branch is proposed the influence of n-butanol extract to SHR blood pressure difference
(n=10)
Blood pressure difference (X ± SD mmHg)
Group
5 days 10 days 15 days
WKY -1.4±2.2 -1.5±5.3 -1.7±10.3
SHR 10.7±10.3
ΔΔΔ 23.5±10.3
ΔΔΔ 29.4±7.4
ΔΔΔ
Treatment group SHR 6.9 ± 9.8 11.5 ± 8.1
*12.0 ± 7.5
***
Compare with SHR
*P<0.05
* *P<0.001
Compare Δ Δ Δ P<0.001 with WKY
Table 3 pressure value, table 4 blood pressure difference t inspection statistics is the result show: the guizhi decoction branch is proposed the effect that n-butanol extract has obvious reduction spontaneous hypertensive rat (SHR) blood pressure,
Above drug efficacy study result shows: Ramulus Cinnamomi Tangyuan County side and branch are carried the gained n-butanol extract, raise for the spontaneous hypertensive rat mouth and all demonstrate tangible hypotensive effect in 5 days, increase antihypertensive effect with administration time and strengthen.Administration 15 days, n-butanol extract group and SHR group relatively have highly significant difference (p<0.001).Its n-butanol extract of laboratory observation does not have obvious influence to the SHR heart rate.
According to the rarely seen single medicinal material n-butanol extract of present relevant report, as Chinese medicine Peucedanum praeruptorum DUNN, Cortex Ilicis Rotundae n-butanol extract, and be that intravenous injection causes that intact animal cat and rat blood pressure reduce, do not see the hypotensive effect report of Chinese medicine compound n-butyl alcohol part, oral administration, also do not see the blood pressure lowering experiment report of the n-butyl alcohol part of single medicinal material or Chinese medicine compound spontaneous hypertensive rat (SHR).
In all age, motherland's clinical disease that is used for the treatment of of medicine is always based on traditional classic prescriptions, curative effect is excellent, so utilize the meticulous Chinese traditional compound medicine of modern science means exploitation, can bring benefit to the mankind, especially reducing hyperpietic M ﹠ M, is that very important meaning is arranged.Essential hypertension is one of all very high disease of China and even countries in the world sickness rate and mortality rate.The present invention on classical ancient prescription guizhi decoction basis, develops the meticulous compound Chinese medicinal preparation that can treat essential hypertension just.Characteristic feature of an invention of the present invention:
1, this invention is the meticulous effective site-n-butanol extract of compound Chinese medicinal preparation;
2, the effect that has definite reduction spontaneous hypertensive rat (SHR) blood pressure;
3, can be used as the patent medicine oral administration, easy to use;
4, its better stability of preparation, curative effect is sure, and toxic and side effects is little;
In a word, up to now, be difficult to find ideal, can be oral, that curative effect is sure, as can to reduce the spontaneous hypertensive rat blood pressure single medicinal material or Chinese medicine compound, this respect research work difficulty is bigger, and the present invention has filled up this blank.
This patent and be published in Chinese experimental pharmacology of Chinese medical formulae magazine .2001 our August in this year, guizhi decoction A part and E in the paper on 7 (4) 20-23 partly compare, and effect of its reduction spontaneous hypertensive rat blood pressure is even better.Its advantage is:
1, n-butanol extract among the present invention partly is not quite similar from chemical preparation aspect and A part and E;
2, it is rapid-action that the present invention reduces the effect of spontaneous hypertensive rat blood pressure, curative effect is more sure, obvious curative effects can occur in 5 days, can reach preferable curative effect in 15 days, and A part and E part need 7 days or the onset of 10 days ability at least, and three weeks of administration are also not as good as n-butanol extract two weeks curative effect of the present invention.This is repeatedly an experimentation gained conclusion.
The specific embodiment:
Take by weighing 1 part of Ramulus Cinnamomi, 1 part of Radix Paeoniae Rubra, 1 part in Fructus Jujubae, 1 part in Rhizoma Zingiberis Recens, Radix Glycyrrhizae Preparata 0.6-0.8 part, add 8 to 10 times distilled water, after water logging half an hour, heating extraction 2 times is boiled 30 minutes after-filtration at every turn, and residue discards, filtrate was reclaimed, and adds 70% ethanol precipitation, through 16-24 hour precipitation, decompress filter, discard residue, get and be dissolved in the ethanol part, reclaim ethanol, with 3-5 times of n-butanol extraction 5-8 time, each 2-3 hour n-butyl alcohol extractum.Use the special equipment spray drying then, 145 ℃ of inlet temperatures, 75 ℃ of outlet temperatures, 1.5 kilograms of pressure.Obtain brown dry powder solid, can be made into tablet, electuary, capsule.Also can be made into liquid preparations such as oral liquid.
Embodiment two:
Press preceding method configuration Ramulus Cinnamomi Tangyuan County side, 3-5 doubly measures n-butyl alcohol by its weight configuration, extracts twice under 100-110 ℃ of temperature, each 6-8 hour, reclaims solvent and gets brownish black n-butyl alcohol extractum.
Embodiment three:
With the Chinese medicine of respectively distinguishing the flavor of in aforementioned Ramulus Cinnamomi Tangyuan County side boil respectively, the molten back of alcohol n-butanol extraction, method as described above, again with each n-butanol extract by former side's proportioning merging.
Embodiment four:
The Chinese medicine of respectively distinguishing the flavor of in aforementioned Ramulus Cinnamomi Tangyuan County side is used twice method of n-butyl alcohol heating extraction respectively as described above, each 6-8 hour, again each n-butanol extract is merged by former side's proportioning.
Claims (5)
1, is used to prevent and treat the cinnamon twig decoction extract of vascular hypertension, it is characterized in that: it be with the raw material of following weight ratio according to following method preparation: raw material: 1 part of Ramulus Cinnamomi, Radix Paeoniae Rubra 0.9-1.1 part, Fructus Jujubae 0.9-1.1 part, Rhizoma Zingiberis Recens 0.9-1.1 part, Radix Glycyrrhizae Preparata 0.6-0.8 part;
Method: above-mentioned raw materials is doubly measured distilled water by weight adding 8-10 for the first time, and post-heating extracted in water logging 30-40 minute, and 100 ℃ were boiled 30 minutes, filtration residue adds 7-9 times of water gaging again, heated and boiled 30 minutes is filtered and is discarded residue, merges twice filtrate and is recycled into extractum; Extractum adds 3 times of amount 70% ethanol, and through 16-24 hour precipitation, decompress filter discarded residue; Alcohol is molten partially recycled, again with n-butanol extraction 5-8 time, each 2-3 hour, reclaim solvent, brownish black n-butyl alcohol extractum.
2, according to the described cinnamon twig decoction extract that is used to prevent and treat vascular hypertension of claim 1, it is characterized in that: the 3-5 by raw material weight doubly disposes n-butyl alcohol, heating extraction under 100-110 ℃ of temperature, and decompression and solvent recovery gets brownish black n-butyl alcohol extractum.
3, according to the described cinnamon twig decoction extract that is used to prevent and treat vascular hypertension of claim 1, it is characterized in that: with the Chinese medicine of respectively distinguishing the flavor of in Ramulus Cinnamomi Tangyuan County side boil respectively, the molten back of alcohol n-butanol extraction, again with each n-butanol extract by former side's proportioning merging.
4, according to the described cinnamon twig decoction extract that is used to prevent and treat vascular hypertension of claim 2, it is characterized in that: the Chinese medicine of respectively distinguishing the flavor of in Ramulus Cinnamomi Tangyuan County side is used the n-butyl alcohol heating extraction respectively, again each n-butanol extract is merged by former side's proportioning.
5, according to claim 1 or the 2 described cinnamon twig decoction extracts that are used to prevent and treat vascular hypertension, it is characterized in that: also comprise the following steps: in the described method n-butyl alcohol extractum special equipment spray drying, 45 ℃ of inlet temperatures, 75 ℃ of outlet temperatures, pressure gets brown dry powder for 1.5 kilograms; In order to prepare various dosage forms.
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