CN1297259C - Total diterpene phenol originated from rosemary, its preparation method and use - Google Patents
Total diterpene phenol originated from rosemary, its preparation method and use Download PDFInfo
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- CN1297259C CN1297259C CNB200410042715XA CN200410042715A CN1297259C CN 1297259 C CN1297259 C CN 1297259C CN B200410042715X A CNB200410042715X A CN B200410042715XA CN 200410042715 A CN200410042715 A CN 200410042715A CN 1297259 C CN1297259 C CN 1297259C
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Abstract
The present invention relates to an effective part of rosemary, a preparing metod and a use thereof. The effective part of rosemary is total phenolic diterpenes extracted from a medicinal material of rosemary, and contains more than 45% of total phenol substance, wherein the main components (carnosol and carnosic acid) account for more than 13% of the total phenol substance. The preparing method comprises the following steps: after drying the rosemary medicinal material in the sun, cutting the dried rosemary medicinal material into segments; adding an extracting solution for extracting the rosemary; after cooling the combined extracting solution, filtering the extracting solution; decolorizing the filtered solution by active carbon; after concentrating the filtered liquid, adding water, filtering the solution, filtering residues, drying and crushing the residues to obtain the total phenolic diterpenes. The effective part of rosemary can be used for preparing medicines for preventing and curing cardiovascular diseases, relieving epigastric pain and curing uterine cancer, cervical carcinoma, intestinal cancer and mammary cancer. The method of extraction of the present invention is simple and practical; the obtained raw medicinal materials have high purity and good color; besides, the effective part of rosemary has the characteristics of low cost and no pollution, and is suitable for industrialization production.
Description
Technical field
The present invention relates to a kind of effective site that derives from Chinese crude drug and its production and use, specifically relate to a kind of total diterpene phenol that derives from the Herba Rosmarini Officinalis medical material and preparation method thereof and its purposes in preparing medicines such as prevention and treatment cardiovascular, alleviation obstruction of qi in the chest and cardialgia disease and treatment uterus carcinoma, cervical cancer, intestinal cancer, breast carcinoma.
Background technology
Herba Rosmarini Officinalis (Rosmarinas officinalis L.) is the herb of Labiatae (Labiatae) Rosmarinus plant, evergreen undershrub, originate in Mediterranean Region, and widely cultivation, various countries, southern Europe such as main product Spain, Morocco, Former Yugoslavia, Bulgaria and Tunisia.In recent years, also there are a large amount of cultivations China part provinces and regions, southwest (Guizhou, Yunnan).Herba Rosmarini Officinalis mainly utilizes the position to be blade, and the blade of gathering with the florescence is good, is elongated shape, green, and fragrant odour is rich in volatile oil in the leaf of Herba Rosmarini Officinalis.
Mainly contain the diterpene phenols component in the Herba Rosmarini Officinalis medical material, also have flavonoid, triterpenes and a small amount of organic acid composition in addition.The diterpene phenols component mainly contains: carnosol, carnosic acid (Wenkekt et al J.Org.chem., 1965,30 (9): 2931), Herba Rosmarini Officinalis phenol (Reiko I.et al Agric.Biol.Chem., 1982,46 (6): 1661-1666), table Herba Rosmarini Officinalis phenol, different Herba Rosmarini Officinalis phenol (Nobuji N.et al Agric.Biol.Chem., 1994,48 (8): 2081-2085) rosmarinic acid etc., with carnosol and carnosic acid is that the Herba Rosmarini Officinalis total diterpene phenolic compound of main component has good interior antioxidation action, it can suppress xanthine/ionic generation of xanthine oxidase system superoxides, also can suppress the peroxidating of microsome and mitochondrion lipid.
Research in the past focuses mostly on Herba Rosmarini Officinalis is being applied to antioxidant, with Herba Rosmarini Officinalis the effective site purposes that is used for preparing prevention and medicines such as treatment cardiovascular and cancer do not appear in the newspapers as yet.
Summary of the invention
One of purpose of the present invention be to provide a kind of derive from Herba Rosmarini Officinalis total diterpene phenols effective site.
Two of purpose of the present invention be to provide described Herba Rosmarini Officinalis the preparation method of total diterpene phenols.
Three of purpose of the present invention be to provide described Herba Rosmarini Officinalis the purposes of total diterpene phenols.
Herba Rosmarini Officinalis provided by the invention the total diterpene phenols, from the Herba Rosmarini Officinalis medical material, extract, the content of its total phenols is more than 45%.Wherein mainly based on carnosol and two chemical compounds of carnosic acid, the content sum of the two is more than 13%.
Herba Rosmarini Officinalis provided by the invention the total diterpene phenols obtain by following method:
1) pretreatment: the Herba Rosmarini Officinalis medical material after will gathering dries the back cutting, and the Herba Rosmarini Officinalis crude drug that obtains is standby;
2) extract: the extracting solution that adds 50～90% (v/v) of 5～12 times of crude drug amounts extracts 1～5 time; The extracting solution that merges is cooled to 20～60 ℃, remove by filter insoluble matter, obtain the filtrate of green and brown color;
3) decolouring: to step 2) add filtrate volume percentage by weight 0.05～0.5% (g/ml) active carbon in the filtrate that obtains,, remove by filter active carbon, clarified, the medicinal liquid of transparent rufous at 30～80 ℃ of decolouring 5～40min;
4) concentrate: it is 1.00～1.10 medicinal liquid that the filtrate that step 3) is obtained is concentrated into relative density, the water that adds 0.4～4 times of crude drug amount, stir, filter, water miscible impurity is dissolved in the filtrate and is removed, the filtering residue drying, pulverize the Herba Rosmarini Officinalis obtain pale yellow powder effective site---total diterpene phenols.
Described step 2) extracting solution is methanol, ethanol, acetone, preferred alcohol;
Described step 2) extracting mode is dipping, percolation or backflow; When selecting the reflux, extract, mode for use, extract 1～4 time, the effect during with 70% ethanol extraction 3 times is the best;
Described step 2) cool preferred 40 ℃ of temperature;
Preferred 0.1% (g/ml) of the addition of the active carbon of described step 3) is best, preferred 55 ℃ of bleaching temperature.
Herba Rosmarini Officinalis provided by the invention total diterpene phenol under oral administration route, can alleviate coronary heart disease, myocardial ischemia that angina pectoris caused effectively, can be used to the medicine for preparing prevention and treatment cardiovascular, alleviates obstruction of qi in the chest and cardialgia disease.
Herba Rosmarini Officinalis provided by the invention total diterpene phenol in body outer screening test, tumor cells such as breast carcinoma, colorectal cancer, melanoma, gastric cancer, leukemia are had and suppress and lethal effect, can be used to prepare the medicine of cancers such as treatment uterus carcinoma, cervical cancer, intestinal cancer, breast carcinoma.
Simple, the easy row of extracting method provided by the invention, with HPLC is detection means, content with carnosol and carnosic acid serves as to detect index, can carry out quality control to whole process flow effectively, reduced the oxidation of effective ingredient self in the effective site effectively, improved content of effective, the crude drug purity height that obtains, color and luster is good; In addition, this extracting method uses conventional extraction equipment, and is cheap, do not use deleterious organic solvent in the technology, pollution-free, helps protecting environment, is suitable for suitability for industrialized production.
Description of drawings
Fig. 1 is that the high performance liquid chromatogram of the Herba Rosmarini Officinalis total diterpene phenol of embodiment 1 preparation detects collection of illustrative plates; Wherein peak 1 is a carnosic acid, and peak 3 is a carnosol;
Fig. 2 is that the thin layer chromatography of the Herba Rosmarini Officinalis total diterpene phenol of embodiment 1 preparation detects collection of illustrative plates; Wherein, 1 is the carnosic acid reference substance, and 2 is the Herba Rosmarini Officinalis effective site of embodiment 1 preparation, and 3 is the carnosol reference substance.
The specific embodiment
The preparation of embodiment 1, Herba Rosmarini Officinalis total diterpene phenol
Herba Rosmarini Officinalis medical material after gathering is dried the back cutting, the alcohol reflux of 70% (v/v) of 10 times of crude drug amounts of adding 3 times; The extracting solution that merges is cooled to 40 ℃, remove by filter insoluble matter, obtain the filtrate of green and brown color; Decolouring: in this filtrate, add the active carbon of filtrate volume percentage by weight 0.1% (g/ml),, remove by filter active carbon, clarified, the medicinal liquid of transparent rufous at 55 ℃ of decolouring 20min; It is 1.10 medicinal liquid that this filtrate is concentrated into relative density, adds the water of 2 times of crude drug amounts, stirs, filter, water miscible impurity is dissolved in the filtrate and is removed, filter residue and drying, pulverizing, obtain Herba Rosmarini Officinalis total diterpene phenol of the present invention, it is a pale yellow powder, and the content of total phenols is 80%.Thin layer chromatography as Fig. 2 detects shown in the collection of illustrative plates, and it mainly contains carnosic acid and two chemical compounds of carnosol, detects as shown in Figure 1 through HPLC, and the content sum of the two is 40%.
The preparation of embodiment 2, Herba Rosmarini Officinalis total diterpene phenol
Herba Rosmarini Officinalis medical material after gathering is dried the back cutting, and the methanol percolation that adds 90% (v/v) of 5 times of crude drug amounts extracts 1 time; The extracting solution that merges is cooled to 60 ℃, remove by filter insoluble matter, obtain the filtrate of green and brown color; Decolouring: in this filtrate, add the active carbon of filtrate volume percentage by weight 0.05% (g/ml),, remove by filter active carbon, clarified, the medicinal liquid of transparent rufous at 30 ℃ of decolouring 40min; It is 1.00 medicinal liquid that this filtrate is concentrated into relative density, the water that adds 0.4 times of crude drug amount, stir, filter, water miscible impurity is dissolved in the filtrate and is removed, filter residue and drying, pulverizing, obtain pale yellow powder, be Herba Rosmarini Officinalis total diterpene phenol of the present invention, it is a pale yellow powder, and the content of total phenols is 45%.The content sum that HPLC detects carnosic acid and carnosol is 13%.
The preparation of embodiment 3, Herba Rosmarini Officinalis total diterpene phenol
Herba Rosmarini Officinalis medical material after gathering is dried the back cutting, and the acetone dipping that adds 50% (v/v) of 12 times of crude drug amounts extracts 5 times; The extracting solution that merges is cooled to 20 ℃, remove by filter insoluble matter, obtain the filtrate of green and brown color; Decolouring: in this filtrate, add the active carbon of filtrate volume percentage by weight 0.5% (g/ml),, remove by filter active carbon, clarified, the medicinal liquid of transparent rufous at 80 ℃ of decolouring 5min; It is 1.05 medicinal liquid that this filtrate is concentrated into relative density, the water that adds 4 times of crude drug amounts, stir, filter, water miscible impurity is dissolved in the filtrate and is removed, filter residue and drying, pulverizing, obtain pale yellow powder, be Herba Rosmarini Officinalis total diterpene phenol of the present invention, it is a pale yellow powder, and the content of total phenols is 60%.It mainly contains carnosic acid and two chemical compounds of carnosol, and the content sum that detects the two through HPLC is 40%.
The Herba Rosmarini Officinalis effective site of embodiment 4, mtt assay vitro detection embodiment 1 suppresses the propagation of different cell lines
1, agents useful for same
The DMEM culture medium: be on the basis of incomplete culture medium, to add 3% Glutamine 1ml, mycillin 10,000 units/ml and 10% serum (time spent adds); Hyclone, calf serum glutamine, penicillin, streptomycin
The ratio of cryopreserving liquid: DMSO and hyclone is 1: 9
MTT: be made into 5mg/ml with pH7.2 PBS, keep in Dark Place, matching while using.
Cell pyrolysis liquid: join with ultra-pure water, contain 20%SDS, 50%DMSO transfers pH4.5
2, used cell line: cancerous cell (KB), leukemia (HL60), cervical cancer cell (HeLa), colorectal cancer cells (HT29), breast cancer cell (MCF7 and MDA231) at the bottom of stomach cancer cell (BGC823), melanoma cell (WM451), the jaw
3, cell culture:
All with the RPMI1640 or the DMEM culture fluid of the hyclone/calf serum that contains 10% deactivation, cell culture went down to posterity once in 37 ℃, 5%CO2 incubator in 2-3 days.
4, the Herba Rosmarini Officinalis effective site (the following Herba Rosmarini Officinalis total diterpene phenol that all is called for short) of embodiment 1 preparation is to the mensuration of different tumor cell proliferation indexs:
Adopt mtt assay to analyze.Collect the conventional tumor cell of cultivating respectively, according to the 2000cells/ hole, 96 orifice plates are inoculated in 4000cells/ hole and 5000cells/ hole, every kind of cell is done 6 repeating holes, cultivation is in containing the DMEM culture medium of 10% hyclone, cultivate after the 24h, supernatant discarded, every hole adds Herba Rosmarini Officinalis total diterpene phenol more respectively, and (drug level is respectively 100 μ g/ml, 50 μ g/ml, 10 μ g/ml, 1 μ g/ml) DMEM 0.1ml, continue to be cultured to 48-72hr and begin to detect, it is the MTT of 500 μ g/ml that every hole adds concentration, cultivate after the 4-6h, the centrifugal supernatant of abandoning of 1900rpm15min adds buffer and each 0.1ml of cell pyrolysis liquid of PBS pH7.2 respectively, after 37 ℃ of overnight incubation, on BioTek Elisa Reader, read the absorption value of OD570nm.The results are shown in table 1.
Table 1, Herba Rosmarini Officinalis total diterpene phenol are to growth of tumour cell suppression ratio (%)
By the result of table 1 as can be seen, Herba Rosmarini Officinalis effective site provided by the invention suppresses all kinds of tumor cell proliferations external, for above-mentioned each cell line stomach cancer cell (BGC823), melanoma cell (WM451), cancerous cell at the bottom of the jaw (KB), leukemia (HL60), cervical cancer cell (HeLa), colorectal cancer cells (HT29), breast cancer cell (MCF7 and MDA231) is in concentration during at 100ug/ml, tumor growth all there is inhibitory action significantly, suppression ratio is all greater than 50%, wherein to breast cancer cell MCF7 concentration when the 10ug/ml, inhibition rate of tumor growth is still greater than 50%.
This experimental result has been pointed out the application of Herba Rosmarini Officinalis effective site provided by the invention in the preparation antitumor drug.
The test of Herba Rosmarini Officinalis effective site aspect cardiac vascular activity of embodiment 5, embodiment 1
1, to the anesthetized dog hemodynamic effects
Experimental technique: 36 of hybrid dogs, be divided into 6 groups, 6 every group, all adopt duodenal administration, administration is grouped as follows:
Experimental group I: Herba Rosmarini Officinalis total diterpene phenol (being the Herba Rosmarini Officinalis effective site of embodiment 1 preparation) 50mg/kg hereinafter to be referred as Herba Rosmarini Officinalis total diterpene phenol;
Experimental group II: Herba Rosmarini Officinalis total diterpene phenol 100mg/kg;
Experimental group III: Herba Rosmarini Officinalis total diterpene phenol 200mg/kg;
Positive controls: DIAOXINXUE KANG 32mg/kg;
Matched group: wait the capacity solvent;
With pentobarbital sodium 30mg/kg i.v. anesthesia hybrid dog, back of the body position is fixing, and skin of neck cuts, and tracheal intubation connects electric pulmotor, separates right carotid, connects the AP-601G amplifier, measures blood pressure.Separate femoral artery, connect the AP-601G amplifier, carry out the ventricle interpolation pipe, measure left indoor pressure, end diastolic pressure, and through maximum the rate of change (± dp/dt of differential processor EQ-601G mensuration left indoor pressure
Max).The 4th intercostal is executed thoracotomy in the left side, exposes heart, cuts off pericardium, does the pericardium art.Separate LCA and aortic root, place the electromagnetic flowmeter probe, measure coronary flow and aorta flow.Extremity connect limb lead, and bioassay standard II leads electrocardiogram, calculate heart rate.Separate duodenum, in order to administration.Above-mentioned each index synchronous recording is in polygraph.Art finishes, and stablize 15min, reach medicine before the record administration after, 30,60,120,150, all indexs of 240min.Before administration and behind the medicine 30,60,120,150,240min gets tremulous pulse, coronary sinus vein blood, measures oxygen content with blood oxygen instrument (Kang Ni-158, produced in USA).And, calculate two-level index: mean arterial pressure, cardiac index, SI, stroke work index, total peripheral resistance, coronary resistance, myocardial oxygen consumption, myocardial oxygen consumption index, myocardium oxygen uptake rate, myocardial flow etc. according to formula.Experimental data measured value and variation fraction values and matched group are relatively organized a t inspection statistics analysis.
Experimental result:
(1) to the influence of myocardial flow: list in table 2, the result shows that the variation percentage rate of reagent Herba Rosmarini Officinalis total diterpene phenol 50mg/kg dosage group myocardial flow significantly increases (P＜0.05) at 60～150min.The variation percentage rate of 100mg/kg dosage group myocardial flow significantly increases (P＜0.05) at 60～240min, the myocardial flow measured value significantly increases (P＜0.05) at 120min.200mg/kg dosage group changes percentage rate at 45～180min and significantly increases (P＜0.01), and measured value significantly increases (P＜0.05) at 90～120min.
(2) to the influence of coronary resistance: list in table 3, the result shows that Herba Rosmarini Officinalis total diterpene phenol 50mg/kg dosage group makes coronary resistance change percentage rate significantly descend at 90～150min (P＜0.05).100mg/kg dosage group changes percentage rate significantly descend at 60～150min (P＜0.05).200mg/kg dosage group changes percentage rate significantly descend (P＜0.01) at 60～240min.
Table 2, Herba Rosmarini Officinalis total diterpene phenol to the influence of dog myocardial flow (ml/100g.min) (X ± S, n=6)
| Group | Dosage mg/kg | Before the administration | After the administration | ||||
| 30 | 60 | 120 | 150 | 240 | |||
| The solvent matched group | 116.17± 29.095 | 113.38± 31.724 | 113.38± 31.724 | 107.30± 27.613 | 109.06± 32.549 | 105.43± 28.256 | |
| ％ | -2.79± 9.557 | -2.79± 9.557 | -7.49± 8.997 | -6.78± 10.143 | -9.21± 11.643 | ||
| DIAOXINXUE KANG | 32 | 124.37± 42.919 | 121.00± 37.687 | 121.00± 37.687 | 145.23± 46.980 | 139.58± 43.431 | 131.02± 48.172 |
| ％ | -1.70± 5.675 | -1.70± 5.675 | 18.32± 17.712 ΔΔ | 13.57± 13.164 Δ | 4.79± 4.947 Δ | ||
| Experimental group I | 50 | 103.27± 19.513 | 104.04± 15.614 | 104.04± 15.614 | 114.94± 11.944 | 115.54± 15.965 | 96.36± 17.093 |
| ％ | 1.55± 6.798 | 1.55± 6.798 | 13.35± 15.165 Δ | 13.88± 17.984 Δ | -6.52± 5.625 | ||
| Experimental group II | 100 | 125.17± 29.010 | 125.01± 26.906 | 125.01± 26.906 | 145.46± 21.873 * | 138.61± 25.498 | 134.67± 23.304 |
| ％ | 0.35±5.324 | 0.35±5.324 | 18.36± 12.346 ΔΔ | 12.74± 15.961 Δ | 9.99± 17.584 Δ | ||
| Experimental group III | 200 | 112.86± 22.604 | 116.11± 18.654 | 116.11± 18.654 | 144.18± 15.805 * | 136.66± 19.758 | 125.46± 18.755 |
| ％ | 3.88± 7.290 | 3.88± 7.290 | 31.92± 27.872 ΔΔ | 23.56± 18.876 ΔΔ | 13.43± 17.428 Δ | ||
Compare * P＜0.05, * * P＜0.01 with normal saline group measured value;
Change percentage comparisons with the normal saline group
ΔP＜0.05,
The Δ ΔP＜0.01 (down together)
Table 3, Herba Rosmarini Officinalis total diterpene phenol to the influence of dog coronary resistance (Kpa/ml/100/min) (X ± S, n=6)
| Group | Dosage mg/kg | Before the administration | After the administration | ||||
| 30 | 60 | 120 | 150 | 240 | |||
| The solvent matched group | 0.11± 0.031 | 0.12± 0.041 | 113.38± 31.724 | 0.12± 0.042 | 109.06± 32.549 | 105.43± 28.256 | |
| ％ | -0.51± 10.463 | -2.79± 9.557 | 3.62± 10.334 | -6.78± 10.143 | -9.21± 11.643 | ||
| DIAOXINXUE KANG | 32 | 0.12± 0.036 | 0.11± 0.032 | 121.00± 37.687 | 0.09± 0.029 | 139.58± 43.431 | 131.02± 48.172 |
| ％ | -1.22± 4.745 | -1.70± 5.675 | -18.31± 13.593 Δ | 13.57± 13.164 Δ | 4.79± 4.947 Δ | ||
| Experimental group I | 50 | 0.14± 0.031 | 0.13± 0.024 | 104.04± 15.614 | 0.11± 0.018 | 115.54± 15.965 | 96.36± 17.093 |
| ％ | -2.03± 7.648 | 1.55± 6.798 | -16.14± 10.950 ΔΔ | 13.88± 17.984 Δ | -6.52± 5.625 | ||
| Experimental group II | 100 | 0.11± 0.028 | 0.11± 0.026 | 125.01± 26.906 | 0.09± 0.015 | 138.61± 25.498 | 134.67± 23.304 |
| ％ | -4.48± 5.392 | 0.35± 5.324 | -17.59± 7.848 ΔΔ | 12.74± 15.961 Δ | 9.99± 17.584 Δ | ||
| Experimental group III | 200 | 0.12± 0.025 | 0.12± 0.026 | 116.11± 18.654 | 0.09± 0.011 | 136.66± 19.758 | 125.46± 18.755 |
| ％ | -5.45± 10.358 | 3.88± 7.290 | -27.16± 15.484 ΔΔ | 23.56± 18.876 ΔΔ | 13.43± 17.428 Δ | ||
Experiment conclusion: above experimental result shows that Herba Rosmarini Officinalis total diterpene phenol 100-200mg/kg dosage can significantly increase myocardial flow, reduce coronary resistance.These effects of Herba Rosmarini Officinalis total diterpene phenol, relevant with direct coronary artery dilating, making it myocardial flow increases, and directly reflects the raising of cardiac pumping function and increases the peripheral blood vessel expansion.
2, the influence of the rat heart muscle ischemia that pituitrin is caused
Get 60 of the healthy SD rats of body weight 220～240g, male and female half and half are divided into 6 groups at random, the blank group, and the diltiazem group (diltiazem, 50mg/kg), DIAOXINXUE KANG JIAONANG (200mg/kg), the high, medium and low dosage group of Herba Rosmarini Officinalis (600,300,150mg/kg).Successive administration 7d, last day is after 30min after the administration is with pentobarbital sodium ip anesthesia, facing upward the position is fixed on the Mus platform, limb lead, electrocardiograph choice criteria voltage 1mv=20mm, chart speed 50mm/s traces normal II and leads behind the electrocardio, annotated in the sublingual vein injection of pituitrin (1U/kg), 5s.Trace the electrocardiogram ECG II of 5s, 15s, 30s, each time point of 3min respectively.
Statistical method: the J point, the T ripple that calculate each time point change and rate of change X ± s, do t check between group.
Experimental result:
(1) rat ECG II J point is changed and the influence of rate of change: list in table 4, the result shows that Herba Rosmarini Officinalis high dose (600mg/kg) can significantly resist the variation (P＜0.01) that J is ordered at 5s and 15s, from rate of change, middle dosage (300mg/kg) relatively has significant difference (P＜0.05) in rate of change and the blank group of 5s and 15s.This result show Herba Rosmarini Officinalis can alleviate cause by myocardial ischemia raising of ordering of J or reduce, its effect is relevant with dosage.
(2) influence that rat ECG II T ripple is changed: list in table 5, the result shows from the T ripple and changes, Herba Rosmarini Officinalis total diterpene phenol high dose group (600mg/kg) and middle dosage group (300mg/kg) change the inhibition (P＜0.05 or P＜0.01) that has in various degree at the right T ripple of different time points, and low dosage can not effectively suppress the T ripple variation that pituitrin causes.This result shows that Herba Rosmarini Officinalis can alleviate the variation of T ripple, and its effect is relevant with dosage.
Table 4, Herba Rosmarini Officinalis cause the influence of rat ECG II J point height change to pituitrin
| Group | Normally | 5s | 15s | 30s | 3min | |
| Blank | 0.80± 0.42 | Change (mm) | 2.95±1.79 | 3.85±1.53 | 1.60±1.26 | 0.95±1.12 |
| Rate of change (%) | 417±346 | 498±287 | 237±219 | 122±130 | ||
| Diltiazem | 0.67± 0.45 | Change (mm) | 0.53±0.75 ** | 0.92±0.93 ** | 1.07±0.92 | 0.80±0.75 |
| Rate of change (%) | 94±147 * | 119±122 ** | 169±119 | 88±83 | ||
| DIAOXINXUE KANG 200mg/kg | 0.70± 0.63 | Change (mm) | 1.90±1.54 | 1.90±1.71 * | 1.25±0.95 | 0.95±0.69 |
| Rate of change (%) | 257±239 | 246±203 * | 161±178 | 79±70 | ||
| Herba Rosmarini Officinalis total diterpene phenol 600mg/kg | 0.60± 0.46 | Change (mm) | 0.90±1.35 ** | 1.55±1.48 ** | 1.8±1.7 | 0.7±0.42 |
| Rate of change (%) | 186±318 | 129±49 ** | 164±138 | 86±48 | ||
| Herba Rosmarini Officinalis total diterpene phenol 300mg/kg | 0.90± 0.74 | Change (mm) | 1.00±1.22 | 2.7±2.08 | 1.40±1.07 | 0.95±0.69 |
| Rate of change (%) | 114±111 * | 250±165 * | 125±109 | 100±76 | ||
| Herba Rosmarini Officinalis total diterpene phenol 150mg/kg | 0.80± 0.79 | Change (mm) | 1.25±1.27 | 2.45±1.66 | 1.55±1.30 | 1.30±0.86 |
| Rate of change (%) | 181±152 | 306±207 | 117±98 | 117±113 |
Table 5, Herba Rosmarini Officinalis cause the influence that rat ECG II T wave height changes to pituitrin
| Group | Normally | 5s | 15s | 30s | 3min | |
| Blank | 1.80± 0.35 | Change (mm) | 2.05±1.96 | 2.80±2.12 | 1.1±1.17 | 0.25±0.42 |
| Rate of change (%) | 108±99 | 162±125 | 73±93 | 13±22 | ||
| Diltiazem | 1.65± 0.34 | Change (mm) | 0.45±0.37 * | 0.55±0.37 ** | 0.75±0.35 | 0.3±0.35 |
| Rate of change (%) | 30±30 * | 33±21 ** | 48±29 | 20±22 | ||
| DIAOXINXUE KANG 200mg/kg | 1.85± 0.47 | Change (mm) | 1.05±0.90 | 0.85±1.00 * | 0.65±0.63 | 0.40±0.39 |
| Rate of change (%) | 61±53 | 54±69 * | 32±29 | 25±31 | ||
| Herba Rosmarini Officinalis total diterpene phenol 600mg/kg | 2.05± 0.50 | Change (mm) | 0.65±0.91 | 0.35±0.82 ** | 0.55±0.50 | 0.55±0.50 |
| Rate of change (%) | 32±45 | 17±40 | 27±24 | 27±24 | ||
| Herba Rosmarini Officinalis total diterpene phenol 300mg/kg | 2.00± 0.41 | Change (mm) | 0.75±0.92 | 1.05±1.36 * | 0.50±0.47 | 0.35±0.41 |
| Rate of change (%) | 40±56 | 53±68 * | 25±23 | 18±19 | ||
| Herba Rosmarini Officinalis total diterpene phenol 150mg/kg | 1.7±0. 75 | Change (mm) | 0.75±0.68 | 1.60±1.26 | 0.55±0.50 | 0.60±0.77 |
| Rate of change (%) | 50±47 | 101±73 | 32±31 | 32±34 |
Experiment conclusion: this experimental result shows, raising or reducing of rat ECG II J point that Herba Rosmarini Officinalis total diterpene phenol 300-600mg/kg causes pituitrin and T ripple has remarkable inhibitory action, show to improve and shrink, cause deficiency myocardial blood supply, thereby suppress myocardial ischemia by coronary artery.
This experimental result has pointed out Herba Rosmarini Officinalis effective site Herba Rosmarini Officinalis total diterpene phenol provided by the invention to prevent and treat cardiovascular in preparation, alleviate the application in the obstruction of qi in the chest and cardialgia disease drug.
Claims (8)
1, a kind of Herba Rosmarini Officinalis total diterpene phenol that from the Herba Rosmarini Officinalis medical material, extracts, it is for to be obtained by following method:
1) pretreatment: the Herba Rosmarini Officinalis medical material after will gathering dries the back cutting, and the Herba Rosmarini Officinalis crude drug that obtains is standby;
2) extract: the extracting solution that adds 50～90v/v% of 5～12 times of crude drug amounts extracts 1～5 time; The extracting solution that merges is cooled to 4～40 ℃, remove by filter insoluble matter, obtain the filtrate of green and brown color; Described extracting solution is methanol, ethanol or acetone;
3) decolouring: to step 2) add filtrate volume percentage by weight 0.05～0.5% active carbon in the filtrate that obtains,, remove by filter active carbon, clarified, the medicinal liquid of transparent rufous at 30～80 ℃ of decolouring 5～40min;
4) concentrate: it is 1.00～1.10 medicinal liquid that the filtrate that step 3) is obtained is concentrated into relative density, add 0.4～4 times to the water of crude drug amount, stir, filter, water miscible impurity is dissolved in the filtrate and is removed, the filtering residue drying, pulverize obtain Herba Rosmarini Officinalis effective site.
2, Herba Rosmarini Officinalis total diterpene phenol as claimed in claim 1 is characterized in that described step 2) extracting solution be ethanol.
3, Herba Rosmarini Officinalis total diterpene phenol as claimed in claim 1 is characterized in that described step 2) extracting mode for the dipping, percolation or backflow.
4, Herba Rosmarini Officinalis total diterpene phenol as claimed in claim 3 is characterized in that, described reflux, extract, method is with 70% ethanol extraction 3 times.
5, Herba Rosmarini Officinalis total diterpene phenol as claimed in claim 1 is characterized in that described step 2) the temperature that cools be 25 ℃.
6, Herba Rosmarini Officinalis total diterpene phenol as claimed in claim 1 is characterized in that, the addition of the active carbon of described step 3) is 0.1%, and bleaching temperature is 50 ℃.
7, the application of the described Herba Rosmarini Officinalis total diterpene of a kind of claim 1 phenol in the medicine for preparing prevention and treatment cardiovascular, alleviation obstruction of qi in the chest and cardialgia disease.
8, the application of the described Herba Rosmarini Officinalis total diterpene of a kind of claim 1 phenol in the medicine of preparation treatment uterus carcinoma, cervical cancer, intestinal cancer, breast carcinoma etc.
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| RU2008143294A (en) * | 2006-04-03 | 2010-05-10 | Нестек С.А. (Ch) | NUTRITIONAL COMPOSITIONS FOR STIMULATING BONE GROWTH AND MAINTAINING HEALTHY BONE AND WAYS CONCERNING THEM |
| CN102697758A (en) * | 2012-06-12 | 2012-10-03 | 昆明理工大学 | Application of cryptomeriol in preparation of anti-tumor angiogenesis medicine |
| BR102014022486B1 (en) * | 2014-09-11 | 2021-03-23 | Universidade Estadual De Campinas - Unicamp | PROCESS OF PURIFICATION OF JAMBU EXTRACT, PURIFIED EXTRACT SO OBTAINED, ANESTHETIC AND BIO ADHESIVE COMPOSITION CONTAINING PURIFIED JAMBU EXTRACT; EUSOS |
| CN104530074A (en) * | 2015-01-07 | 2015-04-22 | 浙江泰康生物科技有限公司 | Method for extracting carnosol from complete salvia |
| BR112020024464A2 (en) * | 2018-06-14 | 2021-03-02 | Mars, Incorporated | support composition for animal with cancer |
| CN113244222B (en) * | 2020-02-12 | 2022-10-25 | 华东师范大学 | Application of carnosol compound in preparing medicine for treating cachexia |
| CN116270798A (en) * | 2023-02-07 | 2023-06-23 | 中国科学院植物研究所 | Use of rosemary extract in synergistic UV radiation for inhibiting proliferation and promoting apoptosis of various cancer cells |
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| CN1113514A (en) * | 1995-01-13 | 1995-12-20 | 金坚敏 | Efficient natural antioxidants and their preparation |
| CN1327038A (en) * | 2001-07-18 | 2001-12-19 | 孙传经 | Process for extracting rosemary antioxidant by super-critical reverse CO2 extraction |
| CN1600353A (en) * | 2003-09-26 | 2005-03-30 | 上海市新文达生物科技有限公司 | Extractive of rosemary, preparation method and application |
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| US5256700A (en) * | 1990-10-06 | 1993-10-26 | Nestec S.A. | Carnosic acid obtention and uses |
| CN1113514A (en) * | 1995-01-13 | 1995-12-20 | 金坚敏 | Efficient natural antioxidants and their preparation |
| CN1327038A (en) * | 2001-07-18 | 2001-12-19 | 孙传经 | Process for extracting rosemary antioxidant by super-critical reverse CO2 extraction |
| CN1600353A (en) * | 2003-09-26 | 2005-03-30 | 上海市新文达生物科技有限公司 | Extractive of rosemary, preparation method and application |
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