CN101530450B - Method for preparing pterocarpus indicus ethanol extract used for endothelium-dependent vasodilation agent and applications of method - Google Patents
Method for preparing pterocarpus indicus ethanol extract used for endothelium-dependent vasodilation agent and applications of method Download PDFInfo
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- CN101530450B CN101530450B CN 200810084961 CN200810084961A CN101530450B CN 101530450 B CN101530450 B CN 101530450B CN 200810084961 CN200810084961 CN 200810084961 CN 200810084961 A CN200810084961 A CN 200810084961A CN 101530450 B CN101530450 B CN 101530450B
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Abstract
The invention relates to a method for preparing pterocarpus santalinus ethanol extract used for endothelium-dependent vasodilator and applications of the extract on the medicine or health products of endothelium-independent vasodilator. The preparation method comprises the steps of extracting the pterocarpus santalinus powders thrice in a back-flow way by 70% of ethanol of 6 times, 5 times and 3 times respectively for 2.5h, 2h and 1.5h, decompressing, concentrating, cooling and drying the extract, and finally obtaining the pterocarpus santalinus extract. Suitable auxiliary material is added into the pterocarpus santalinus extract so as to prepare the medicines or health products such as powder injection, drops, troche, capsule, oral liquid, grain agents and the like.
Description
Technical field
The present invention relates to a kind of red sandalwood ethanol extraction as direct vasodilation, and this extract is in the medicine of the cardiovascular disease such as treatment hypertension or the application in the health product.
Background technology
Blood vessel endothelium also has active metabolism endocrine function except because plaing the physiologic barrier effect between blood and vascular smooth muscle, to keep the balance of environment in the blood vessel.Endothelium-dependent vasodilatation (Endothelium-dependentVasodilation, EDD) be one of blood vessel endothelium critical function, its functional disorder, early origin, development and complication to atherosclerosis (Atherosclerosis, AS) especially cardiovascular disease play mastery reaction.
Vasodilation has dual mode: EDD: refer to that 1. endotheliocyte is at chemical substance such as acetylcholine, discharge EDRF under the effect of Kallidin I etc. or physiological stimulation (such as reactive hyperemia) and cause vasodilation, it depends on structural integrity and normally functioning endotheliocyte, normal EDD function can be kept antiotasis, anticoagulant, suppress mononuclear cell and neutrophil(e) cell and adhere to, suppress vascular SMC propagation; 2. dependent/non-dependent vasodilation (or claim smooth muscle dependency vasodilation): refer to that exogenous NO precursor such as the medicines such as nitroglycerin, sodium nitroprusside do not rely on blood vessel endothelium, directly the caused vasodilation of NO vasoactive SMC of release.Dual mode is both independent, and is unified again, jointly finishes the diastolic function of blood vessel.Confirm that now EDRF is exactly NO, it comes from arginine metabolism, and the active of nitricoxide synthase (NOSynthase, NOS) directly affects the synthetic of NO and discharge, and ET-1 is the strongest contracting Angiogenesis that endotheliocyte generates, and its physiological action is opposite with NO.Such as endothelial injury, reduce medicine and physiological stimulation are reactive, cause the NO synthesis secretion and reduce, vasodilation is unusual and weaken, and shows as vasospasm or shrink to strengthen.
Existingly studies show that following medicine may improve vascular endothelial function or EDD function.
1, the improvement mechanism of HCG-COA reductase inhibitor lipid-lowering statins is except generating with cholesterol reducing, minimizing superoxide anion, outside the Pass minimizing NO inactivation has, also stimulate under state and the base state endothelium relevant to the expansion vascular reaction of NO with its enhancing, namely also have unique non-effect for reducing fat with it, as improve endothelial function, stablize atheromatous plaque, minimizing platelet aggregation or antithrombotic, antiinflammatory or antioxidation.
2, angiotensin converting enzyme suppresses the activation of machine agent (ACEI) renin-angiotensin system (RAS), make endothelial hypofunction by making to increase in the blood with two approach of Kallidin I decomposition acceleration, ACEI, itself also can suppress Kallidin I and decompose because of the damage of RAS activation to endothelium by antagonism.
3, thereby the antioxidant antioxidant can be offset the Oxidation protection endothelial function of superoxide anion.The antioxidant of having generally acknowledged at present has vitamin C, E, tocopherol etc.
Take large doses of vitamin C (2g) remarkable impaired EDD function behind the high-fat meal is had protective effect.
4, endothelin-receptor antagonists endothelin receptor, the endogenous vasoconstriction mechanism that exists when antagonist is based on endothelial injury are used and are given birth to, find to have ET-A and two kinds of receptor subtypes of ET-B can mediate the pressurization of Endothelin at SMC, blood vessel endothelium also has the ET-B receptor and can mediate EDD by discharging NO and PGI.
5, L-arginine can be converted into NO and bring into play physiological effect with the NOS effect in vivo as the precursor of NO;
And present stage is used as the vasodilation that endothelium relies on to the red sandalwood ethanol extraction, yet there are no report.
The botanical term of Lignum pterocarpi indici is red sandalwood, is the pulse family Pterocarpus.Latin is called Pterocarpussantalinus L.F, and commodity are called red sanders, red sandal-wood.
Its timber can make body shrink, to augment and diaphoresis. the timber of pasty state is as cold therapy inflammation and headache. it is said that this is to help treat depression and dermatosis. the medicine of enduring out is as astringent cardiac tonic chronic dysentery bark powder gruel, to be used for the treatment of diarrhoea. to drink and Lignum pterocarpi indici water every day be used for the treatment of diabetes twice. the locality is also referred to as rakthachandan. other timber and barks with generic, and Pterocarpus marsupium Roxb. P.marsupium is on record hypoglycemic activity.
Li Shizhen (1518-1593 A.D.) Compendium of Material Medica our department of the Ming Dynasty the 34 volume is said: " Lignum pterocarpi indici-salty is slightly cold, and is nontoxic, energy and ying-qi detumescence poison.Available this sawdust is fried in shallow oil water and is smeared the affected part; And have relax through invigorate blood circulation, blood circulation promoting and antihypertensive effect.
But present stage is treated hypertensive medicine or health product with the red sandalwood ethanol extraction as vasodilation, yet there are no report.
Summary of the invention
1. the present invention has confirmed that the Lignum pterocarpi indici extract to the dilating effect of animal thoracic aortic ring blood vessel that endothelium arranged, has great clinical meaning to Cardiovarscular.
2. the present invention can obtain by following method: with 70% alcohol reflux of 6 times, 5 times and 3 times three times, each time is respectively 2.5h, 2h and 1.5h respectively, concentrating under reduced pressure, and cool drying gets the Lignum pterocarpi indici extract.
3. the invention provides effective dosage that the Lignum pterocarpi indici extract can make the interior cutaneous vessel expansion.
4. the Lignum pterocarpi indici extract among the present invention can be mixed and made into preparation mutually with pharmaceutically acceptable excipient, carrier, buffer agent and/or stabilizing agent.Comprise peroral dosage form, tablet, capsule, oral liquid, granule etc. are arranged, and injection type, injection and powder ampoule agent for injection etc. are arranged.
5. the invention provides the route of administration that the Lignum pterocarpi indici extract can make interior cutaneous vessel expansion, can be oral, injection or other approach.
6. the Lignum pterocarpi indici among the present invention is red sandalwood, India Lignum pterocarpi indici, Pterocarpus marsupium Roxb. or kiaat.
7. the invention provides medicine or the application of health product in treatment hypertension, coronary heart disease, apoplexy and myocardial infarction of the preparation of Lignum pterocarpi indici extract
The specific embodiment
Embodiment 1: concentration is the vasoconstrictor effects of the inhibition phyenlephrinium that relies on of the ethanol extraction endothelium of 0.0025g/ml Lignum pterocarpi indici
Test method:
The chest large artery trunks ring of mouse is adopted by present test.To prepare thing normal saline solution oxidation, then mix with following synthetic: 1. sodium chloride (119); 2. potassium chloride (4.7); 3. potassium dihydrogen phosphate (1.2); 4. magnesium sulfate (1.2); 5. sodium bicarbonate (25); 6. calcium chloride (1.6); 7. glucose (11) keeps 4 degrees centigrade temperature.Prepare two radicular arteries rings (every long 4 millimeters), remove endothelium, it is inner surperficial to rub gently with a smooth waddy, successfully removes interior micromicro and confirms by following method: large artery trunks ring and phyenlephrinium (1 μ M) lack the lax reaction to acetylcholine when meeting.The isometric stretching that the myograph system that processes with computer records the large artery trunks ring.After the balance through 90 minutes preloading of at least 1.5 grams (this is preloading best in our the previous test), twice challenge that arterial ring faces 60 milliliters potassium chloride in 30 minutes interval is to set up a contractile reaction baseline.
Lax percentage with lax reflection Forskohlin recently calculates.The relaxation curve of the accumulation reaction density of Lignum pterocarpi indici ethanol extraction has just produced, and the lax of the water of Lignum pterocarpi indici extract and ethanol is that endothelium relies on and the non-dependence of endothelium.
Result of the test:
0.0025g/ml the ethanol extraction of Lignum pterocarpi indici, to by the pretreated vasodilator effect that large artery trunks ring endothelium, complete is arranged of phyenlephrinium, be equivalent to 1 μ M Forskohlin lax effect 4%.
Embodiment 2: concentration is the vasoconstrictor effects of the inhibition phyenlephrinium that relies on of the ethanol extraction endothelium of 0.004g/ml Lignum pterocarpi indici
Test method:
The chest large artery trunks ring of mouse is adopted by present test.To prepare thing normal saline solution oxidation, then mix with following synthetic: 1. sodium chloride (119); 2. potassium chloride (4.7); 3. potassium dihydrogen phosphate (1.2); 4. magnesium sulfate (1.2); 5. sodium bicarbonate (25); 6. calcium chloride (1.6); 7. glucose (11) keeps 4 degrees centigrade temperature.Prepare two radicular arteries rings (every long 4 millimeters), remove endothelium, it is inner surperficial to rub gently with a smooth waddy, successfully removes interior micromicro and confirms by following method: large artery trunks ring and phyenlephrinium (1 μ M) lack the lax reaction to acetylcholine when meeting.The isometric stretching that the myograph system that processes with computer records the large artery trunks ring.After the balance through 90 minutes preloading of at least 1.5 grams (this is preloading best in our the previous test), twice challenge that arterial ring faces 60 milliliters potassium chloride in 30 minutes interval is to set up a contractile reaction baseline.
Lax percentage with lax reflection Forskohlin recently calculates.The relaxation curve of the accumulation reaction density of Lignum pterocarpi indici ethanol extraction has just produced, and the lax of the water of Lignum pterocarpi indici extract and ethanol is that endothelium relies on and the non-dependence of endothelium.
Result of the test:
0.004g/ml the ethanol extraction of Lignum pterocarpi indici, to by the pretreated vasodilator effect that large artery trunks ring endothelium, complete is arranged of phyenlephrinium, be equivalent to 1 μ M Forskohlin lax effect 9%.
Embodiment 3: concentration is the vasoconstrictor effects of the inhibition phyenlephrinium that relies on of the ethanol extraction endothelium of 0.006g/ml Lignum pterocarpi indici
Test method:
The chest large artery trunks ring of mouse is adopted by present test.To prepare thing normal saline solution oxidation, then mix with following synthetic: 1. sodium chloride (119); 2. potassium chloride (4.7); 3. potassium dihydrogen phosphate (1.2); 4. magnesium sulfate (1.2); 5. sodium bicarbonate (25); 6. calcium chloride (1.6); 7. glucose (11) keeps 4 degrees centigrade temperature.Prepare two radicular arteries rings (every long 4 millimeters), remove endothelium, it is inner surperficial to rub gently with a smooth waddy, successfully removes interior micromicro and confirms by following method: large artery trunks ring and phyenlephrinium (1 μ M) lack the lax reaction to acetylcholine when meeting.The isometric stretching that the myograph system that processes with computer records the large artery trunks ring.After the balance through 90 minutes preloading of at least 1.5 grams (this is preloading best in our the previous test), twice challenge that arterial ring faces 60 milliliters potassium chloride in 30 minutes interval is to set up a contractile reaction baseline.
Lax percentage with lax reflection Forskohlin recently calculates.The relaxation curve of the accumulation reaction density of Lignum pterocarpi indici ethanol extraction has just produced, and the lax of the water of Lignum pterocarpi indici extract and ethanol is that endothelium relies on and the non-dependence of endothelium.
Result of the test:
0.006g/ml the ethanol extraction of Lignum pterocarpi indici, to by the pretreated vasodilator effect that large artery trunks ring endothelium, complete is arranged of phyenlephrinium, be equivalent to 1 μ M Forskohlin lax effect 16%.
Embodiment 4: concentration is the vasoconstrictor effects of the inhibition phyenlephrinium that relies on of the ethanol extraction endothelium of 0.012g/ml Lignum pterocarpi indici
Test method:
The chest large artery trunks ring of mouse is adopted by present test.To prepare thing normal saline solution oxidation, then mix with following synthetic: 1. sodium chloride (119); 2. potassium chloride (4.7); 3. potassium dihydrogen phosphate (1.2); 4. magnesium sulfate (1.2); 5. sodium bicarbonate (25); 6. calcium chloride (1.6); 7. glucose (11) keeps 4 degrees centigrade temperature.Prepare two radicular arteries rings (every long 4 millimeters), remove endothelium, it is inner surperficial to rub gently with a smooth waddy, successfully removes interior micromicro and confirms by following method: large artery trunks ring and phyenlephrinium (1 μ M) lack the lax reaction to acetylcholine when meeting.The isometric stretching that the myograph system that processes with computer records the large artery trunks ring.After the balance through 90 minutes preloading of at least 1.5 grams (this is preloading best in our the previous test), twice challenge that arterial ring faces 60 milliliters potassium chloride in 30 minutes interval is to set up a contractile reaction baseline.
Lax percentage with lax reflection Forskohlin recently calculates.The relaxation curve of the accumulation reaction density of Lignum pterocarpi indici ethanol extraction has just produced, and the lax of the water of Lignum pterocarpi indici extract and ethanol is that endothelium relies on and the non-dependence of endothelium.
Result of the test:
0.012g/ml the ethanol extraction of Lignum pterocarpi indici, to by the pretreated vasodilator effect that large artery trunks ring endothelium, complete is arranged of phyenlephrinium, be equivalent to 1 μ M Forskohlin lax effect 20%.
Embodiment 5: concentration is the vasoconstrictor effects of the inhibition phyenlephrinium that relies on of the ethanol extraction endothelium of 0.016g/ml Lignum pterocarpi indici
Test method:
The chest large artery trunks ring of mouse is adopted by present test.To prepare thing normal saline solution oxidation, then mix with following synthetic: 1. sodium chloride (119); 2. potassium chloride (4.7); 3. potassium dihydrogen phosphate (1.2); 4. magnesium sulfate (1.2); 5. sodium bicarbonate (25); 6. calcium chloride (1.6); 7. glucose (11) keeps 4 degrees centigrade temperature.Prepare two radicular arteries rings (every long 4 millimeters), remove endothelium, it is inner surperficial to rub gently with a smooth waddy, successfully removes interior micromicro and confirms by following method: large artery trunks ring and phyenlephrinium (1 μ M) lack the lax reaction to acetylcholine when meeting.The isometric stretching that the myograph system that processes with computer records the large artery trunks ring.After the balance through 90 minutes preloading of at least 1.5 grams (this is preloading best in our the previous test), twice challenge that arterial ring faces 60 milliliters potassium chloride in 30 minutes interval is to set up a contractile reaction baseline.
Lax percentage with lax reflection Forskohlin recently calculates.The relaxation curve of the accumulation reaction density of Lignum pterocarpi indici ethanol extraction has just produced, and the lax of the water of Lignum pterocarpi indici extract and ethanol is that endothelium relies on and the non-dependence of endothelium.
Result of the test:
0.016g/ml the ethanol extraction of Lignum pterocarpi indici, to by the pretreated vasodilator effect that large artery trunks ring endothelium, complete is arranged of phyenlephrinium, be equivalent to 1 μ M Forskohlin lax effect 25%.
Embodiment 6: concentration is the vasoconstrictor effects of the inhibition phyenlephrinium that relies on of the ethanol extraction endothelium of 0.021g/ml Lignum pterocarpi indici
Test method:
The chest large artery trunks ring of mouse is adopted by present test.To prepare thing normal saline solution oxidation, then mix with following synthetic: 1. sodium chloride (119); 2. potassium chloride (4.7); 3. potassium dihydrogen phosphate (1.2); 4. magnesium sulfate (1.2); 5. sodium bicarbonate (25); 6. calcium chloride (1.6); 7. glucose (11) keeps 4 degrees centigrade temperature.Prepare two radicular arteries rings (every long 4 millimeters), remove endothelium, it is inner surperficial to rub gently with a smooth waddy, successfully removes interior micromicro and confirms by following method: large artery trunks ring and phyenlephrinium (1 μ M) lack the lax reaction to acetylcholine when meeting.The isometric stretching that the myograph system that processes with computer records the large artery trunks ring.After the balance through 90 minutes preloading of at least 1.5 grams (this is preloading best in our the previous test), twice challenge that arterial ring faces 60 milliliters potassium chloride in 30 minutes interval is to set up a contractile reaction baseline.
Lax percentage with lax reflection Forskohlin recently calculates.The relaxation curve of the accumulation reaction density of Lignum pterocarpi indici ethanol extraction has just produced, and the lax of the water of Lignum pterocarpi indici extract and ethanol is that endothelium relies on and the non-dependence of endothelium.
Result of the test:
0.021g/ml the ethanol extraction of Lignum pterocarpi indici, to by the pretreated vasodilator effect that large artery trunks ring endothelium, complete is arranged of phyenlephrinium, be equivalent to 1 μ M Forskohlin lax effect 31%.
Embodiment 7: concentration is the vasoconstrictor effects of the inhibition phyenlephrinium that relies on of the ethanol extraction endothelium of 0.031g/ml Lignum pterocarpi indici
Test method:
The chest large artery trunks ring of mouse is adopted by present test.To prepare thing normal saline solution oxidation, then mix with following synthetic: 1. sodium chloride (119); 2. potassium chloride (4.7); 3. potassium dihydrogen phosphate (1.2); 4. magnesium sulfate (1.2); 5. sodium bicarbonate (25); 6. calcium chloride (1.6); 7. glucose (11) keeps 4 degrees centigrade temperature.Prepare two radicular arteries rings (every long 4 millimeters), remove endothelium, it is inner surperficial to rub gently with a smooth waddy, successfully removes interior micromicro and confirms by following method: large artery trunks ring and phyenlephrinium (1 μ M) lack the lax reaction to acetylcholine when meeting.The isometric stretching that the myograph system that processes with computer records the large artery trunks ring.After the balance through 90 minutes preloading of at least 1.5 grams (this is preloading best in our the previous test), twice challenge that arterial ring faces 60 milliliters potassium chloride in 30 minutes interval is to set up a contractile reaction baseline.
Lax percentage with lax reflection Forskohlin recently calculates.The relaxation curve of the accumulation reaction density of Lignum pterocarpi indici ethanol extraction has just produced, and the lax of the water of Lignum pterocarpi indici extract and ethanol is that endothelium relies on and the non-dependence of endothelium.
Result of the test:
0.031g/ml the ethanol extraction of Lignum pterocarpi indici, to by the pretreated vasodilator effect that large artery trunks ring endothelium, complete is arranged of phyenlephrinium, be equivalent to 1 μ M Forskohlin lax effect 39%.
Claims (8)
1. the vasodilation of an endothelium dependence is characterized in that as the application of preparation treatment cardiovascular and cerebrovascular diseases medicament: described medicine adopts Lignum pterocarpi indici or its to belong to extract and the acceptable excipient of pharmacy, carrier, buffer agent and/or the stabilizing agent of thing together.
2. application according to claim 1 is characterized in that: describedly belong to all floristics that thing is the pulse family Pterocarpus together.
3. application according to claim 1 is characterized in that: extracting the used solvent of Lignum pterocarpi indici is ethanol.
4. application according to claim 1 is characterized in that: the dosage form of described medicine adopts any dosage form of approving on the pharmaceutics.
5. according to claim 1～4 described application is characterized in that: described application is the application in the hypertensive medicine of preparation treatment.
6. according to claim 1～4 described application is characterized in that: described application is the application in the medicine of preparation treatment coronary heart disease.
7. according to claim 1～4 described application is characterized in that: described application is the application in the medicine of preparation prevention and treatment apoplexy.
8. according to claim 1～4 described application is characterized in that: described application is the application in the medicine of preparation prevention and treatment myocardial infarction.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104479398A (en) * | 2014-12-16 | 2015-04-01 | 常州美胜生物材料有限公司 | Pterocarpus santalinus extract and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104448917B (en) * | 2014-12-22 | 2016-05-11 | 长沙理工大学 | A kind of method that adopts acetic acid-microwave technique to extract the red wooden carthamin that continues |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1106291A (en) * | 1994-02-04 | 1995-08-09 | 白玛加措 | Tibetan drug and its prepn. |
| CN1827156A (en) * | 2005-11-09 | 2006-09-06 | 端智 | Consciousness-restoring tablet with pearl |
Non-Patent Citations (3)
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| 余韵星，乔士湖，鲁永新.心痛证治初探.《江西中医药》.1995,增刊. * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104479398A (en) * | 2014-12-16 | 2015-04-01 | 常州美胜生物材料有限公司 | Pterocarpus santalinus extract and preparation method and application thereof |
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