Summary of the invention
The purpose of this invention is to provide a kind of compositions for prevention or treatment apoplexy, the defects that exists to overcome prior art.
Compositions for prevention or treatment apoplexy provided by the invention comprises following component by weight:
Arasaponin R1 4.8-10 part
Ginsenoside Rg1 19.8-45 part
Ginsenoside Rb1 20-40 part
Ginsenoside Re 3.5-6 part
Ginsenoside Rd 1.5-9.9 part.
Preferably, described compositions comprises following component by weight:
Arasaponin R1 4.8-7 part
Ginsenoside Rg1 19.8-45 part
Ginsenoside Rb1 20-40 part
Ginsenoside Re 3.5-4.7 part
Ginsenoside Rd 1.5-7.9 part.
Preferably, described compositions comprises following component by weight:
Arasaponin R1 4.8-7 part
Ginsenoside Rg1 19.8-45 part
Ginsenoside Rb1 20-40 part
Ginsenoside Re 3.5-4.7 part
Ginsenoside Rd 1.5-4.9 part.
Preferably, described compositions comprises following component by weight:
Arasaponin R1 4.8-7 part
Ginsenoside Rg1 25-45 part
Ginsenoside Rb1 20-40 part
Ginsenoside Re 3.5-4.7 part
Ginsenoside Rd 1.5-4.9 part.
Preferably, described compositions comprises following component by weight:
Arasaponin R1 4.8-7 part
Ginsenoside Rg1 25-45 part
Ginsenoside Rb1 20-40 part
Ginsenoside Re 3.5-4.7 part
Ginsenoside Rd 2.6-3.9 part.
The present invention also provides the method for preparing above-mentioned composition, comprise the steps: the Radix Notoginseng appropriateness is pulverized, adding the 70%-90% alcohol heat reflux extracts, be concentrated into without the alcohol flavor, thin up precipitation 12-24 hour is filtered, and filtrate is through resin absorption, be that 20%, 40%, 60%, 80% and 95% ethanol carries out gradient elution with volume ratio successively, flow velocity is 8ml/min.Eluent silica gel H thin-layer chromatographic analysis, developing solvent are " n-butyl alcohol-ethyl acetate-water " 5: 0.5: 4, and volume ratio is 10% ethanol solution of sulfuric acid colour developing.Merge chromatograph speckle same composition, decompression and solvent recovery.Upper chromatography silicagel column, with " chloroform-methanol-water " mixed solvent eluting of different proportion, flow velocity is 8ml/min.Merge chromatograph speckle same composition, decompression and solvent recovery, respectively highly purified arasaponin R1, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Re and ginsenoside Rd.Above-mentioned five components in certain proportion mixing is namely got compositions.
The present invention also provides and comprises above-mentioned composition and the preparation of available support pharmaceutically.
The present invention also provides above-mentioned composition for the preparation of the application in the medicine of the content that reduces homocysteine in blood plasma.
The present invention further provides above-mentioned composition for the preparation of the application in the medicine of regulating blood pressure.
The present invention further provides above-mentioned composition for the preparation of the prevention or the treatment apoplexy medicine in application.
Chinese medicine composition of the present invention has following beneficial effect:
1) ginsenoside Rd is except collaborative other component co-therapy apoplexies, in above-mentioned content ratio scope, also can significantly reduce the content of homocysteine in blood plasma and the effect of regulating blood pressure is arranged, the effective second generation of the generation of prevention of stroke disease and apoplexy, and in the process for the treatment of apoplexy capable of regulating blood pressure, shorten the course of disease, alleviate ailing.
2) ginsenoside Rg1 can set up fast, improve learning and memory, slow down aging, has the stimulating central nervous system effect, suppresses the platelet aggregation effect.The ginsenoside Rb1 has the function that strengthens the choline system, increases the synthetic and release of acetylcholine and improves the memory effect.The ginsenoside Re has the inhibition nervus centralis, promotes DNA, and RNA is synthetic.The effect of rising plasma corticosterone, blood vessel dilating.
3) five composition combinations have blood vessel dilating, reduce myocardial oxygen consumption, suppress platelet aggregation, prolong the effects such as clotting time, blood fat reducing, removing free radical, antiinflammatory, antioxidation.
4) with like product relatively, compositions of the present invention can effectively be prevented, be treated apoplexy, and more remarkable effect, safety higher, can significantly shorten the course of disease, alleviate ailing.
The specific embodiment
Following examples are used for explanation the present invention, but are not used for limiting the scope of the invention.
Embodiment 1
The extraction of component:
Radix Notoginseng raw medicinal herbs 1000g is ground into coarse powder, adds 2.5 times of amount 90% ethanol, heating and refluxing extraction is evaporated to without the alcohol flavor.Thin up left standstill 24 hours to 0.3g (crude drug)/ml, filtered.Filtrate is used 20%, 40%, 60%, 80% and 95% (volume ratio) ethanol gradient elution successively by macroporous adsorptive resins, and flow velocity 8ml/min collects with every part of 500ml.Eluent silica gel H thin-layer chromatographic analysis, developing solvent are " n-butyl alcohol-ethyl acetate-water " 5: 0.5: 4 (upper strata), the colour developing of 10% (volume ratio) ethanol solution of sulfuric acid.Merge chromatograph speckle same composition, decompression and solvent recovery.Go up the chromatography silicagel column, using successively " chloroform-methanol-water " is 80: 18: 2,75: 20: 5,65: 30: 5,60: 33: 7,54: 38: 8 solvent elution again, and flow velocity 8ml/min collects with every part of 500ml.Eluent silica gel H thin-layer chromatographic analysis, developing solvent is the same.Merge chromatograph speckle same composition, decompression and solvent recovery, respectively highly purified above-mentioned each component.
With the acetonitrile-water gradient elution, acetonitrile: 0-20min, 18%-20% (volume ratio); 20-45min, 20-45% (volume ratio); 45-55min, 45-55% (volume ratio).Flow velocity 1.5ml/min detects wavelength 203nm, and sample size 10 μ l, column temperature are that 25 ℃ method detects above-mentioned each composition.
The separation and Extraction Panax Notoginseng saponin R
13.67g, Panax Notoginseng saponin R wherein
1Content be 96.8%.
Separation and Extraction ginsenoside Rg
114.25g, ginsenoside Rg wherein
1Content be 95.9%.
Separation and Extraction ginsenoside Re 1.45g, wherein ginsenoside Re's content is 96.1%.
Separation and Extraction ginsenoside Rb
113.4g, ginsenoside Rb wherein
1Content be 96.2%.
Separation and Extraction ginsenoside Rd 3.25g, wherein ginsenoside Rd's content is 95.6%.
Take by weighing each component (the basic pure component that makes as stated above) of following weight: arasaponin R1 7g, ginsenoside Rg1 25g, ginsenoside Rb1 30g, ginsenoside Re 4.7g, ginsenoside Rd 7.9g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with water for injection, add the needle-use activated carbon decolouring, filter, inject water to total amount, regulate pH value to 6.5, filter, and lyophilization, and get final product.
Embodiment 2
Take by weighing each component of following weight: arasaponin R1 4.8g, ginsenoside Rg1 19.8g, ginsenoside Rb1 20g, ginsenoside Re 3.5g, ginsenoside Rd 1.5g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with water for injection, add the needle-use activated carbon decolouring, filter, inject water to total amount, regulate pH value to 6.0, filter, and lyophilization, and get final product.
Embodiment 3
Take by weighing each component of following weight: arasaponin R1 10g, ginsenoside Rg1 45g, ginsenoside Rb1 40g, ginsenoside Re 6g, ginsenoside Rd 9.9g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with water for injection, add the needle-use activated carbon decolouring, filter, inject water to total amount, regulate pH value to 7.0, filter, and lyophilization, and get final product.
Embodiment 4
Take by weighing each component of following weight: arasaponin R1 7g, ginsenoside Rg1 25g, ginsenoside Rb1 30g, ginsenoside Re 4.7g, ginsenoside Rd 7.9g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with water for injection, add the needle-use activated carbon decolouring, filter, inject water to total amount, regulate pH value to 6.5, filter, and lyophilization, and get final product.
Embodiment 5
Take by weighing each component of following weight: arasaponin R1 5g, ginsenoside Rg1 35g, ginsenoside Rb1 33g, ginsenoside Re 4.0g, ginsenoside Rd 4.9g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with water for injection, add the needle-use activated carbon decolouring, filter, inject water to total amount, regulate pH value to 6.8, filter, and lyophilization, and get final product.
Embodiment 6
Take by weighing each component of following weight: arasaponin R1 9g, ginsenoside Rg1 30g, ginsenoside Rb1 35g, ginsenoside Re 5g, ginsenoside Rd 3.9g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with water for injection, add the needle-use activated carbon decolouring, filter, inject water to total amount, regulate pH value to 6.7, filter, and lyophilization, and get final product.
Embodiment 7
Take by weighing each component of following weight: arasaponin R1 8g, ginsenoside Rg1 40g, ginsenoside Rb1 38g, ginsenoside Re 5.5g, ginsenoside Rd 2.6g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with water for injection, add the needle-use activated carbon decolouring, filter, inject water to total amount, regulate pH value to 6.6, filter, and lyophilization, and get final product.
Embodiment 8
Take by weighing each component of following weight: arasaponin R1 8.5g, ginsenoside Rg1 32g, ginsenoside Rb1 36g, ginsenoside Re 4.5g, ginsenoside Rd 6g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with water for injection, add the decolouring of 0.5% needle-use activated carbon, filter, add to the full amount of water for injection, transfer pH to 6.5, filter, and fill, sterilization namely gets small-volume injection.
Embodiment 9
Take by weighing each component of following weight: arasaponin R1 8.5g, ginsenoside Rg1 32g, ginsenoside Rb1 36g, ginsenoside Re 4.5g, ginsenoside Rd 6g.
Preparation method is as follows: above-mentioned each component mixed, with the dissolving of 0.9% sodium chloride injection, adds the decolouring of 0.5% needle-use activated carbon, filter, add the chlorination sodium injection to 1000ml, transfer pH6.5, filter, and fill, sterilization namely gets bulk capacity injection.
Embodiment 10
Take by weighing each component of following weight: arasaponin R1 8.5g, ginsenoside Rg1 32g, ginsenoside Rb1 36g, ginsenoside Re 4.5g, ginsenoside Rd 6g.
Preparation method is as follows: above-mentioned each component mixed, dissolves in right amount with 5% glucose injection, add the decolouring of 0.5% needle-use activated carbon, filter, add 5% glucose injection to 1000ml, transfer pH6.5, filter, and fill, sterilization namely gets bulk capacity injection.
Embodiment 11
Take by weighing each component of following weight: arasaponin R1 8.5g, ginsenoside Rg1 32g, ginsenoside Rb1 36g, ginsenoside Re 4.5g, ginsenoside Rd 6g.
Preparation method is as follows: above-mentioned each component mixed, further is ground into fine powder, cross 300 mesh sieves, add composition weight 76% starch, and mixing, granulation incapsulates after adding composition weight 4% Pulvis Talci mixes evenly, namely gets capsule.
Embodiment 12
Take by weighing each component of following weight: arasaponin R1 8.5g, ginsenoside Rg1 32g, ginsenoside Rb1 36g, ginsenoside Re 4.5g, ginsenoside Rd 6g.
Preparation method is as follows: above-mentioned each component is mixed, further be ground into fine powder, add composition weight 70% dextrin, mixing, granulation adds the mixed evenly rear sheet of beating of composition weight 1% Pulvis Talci and composition weight 1% magnesium stearate, packing namely gets tablet.
Embodiment 13
Take by weighing each component of following weight: arasaponin R1 8.5g, ginsenoside Rg1 32g, ginsenoside Rb1 36g, ginsenoside Re 4.5g, ginsenoside Rd 6g.
Preparation method is as follows: above-mentioned each component mixed, further is ground into fine powder, add 2 times of sucrose of composition weight, and mixing, granulation, packing, packing namely gets granule.
The protective effect of 1 pair of controlled hypotension brain injury of experimental example
1, method and grouping
The healthy adult male rat, body weight 250~350g, fasting 12h freely drinks water.The chloral hydrate intraperitoneal anesthesia, after the rat peace and quiet it being lain on the back places on the operating-table and fixing head and extremity; Put into homemade oropharyngeal airway in the oral cavity to keep respiratory passage unblocked; Anus temperature meter is put into the rat anal, and shines rat with electric filament lamp, keeps the anus temperature in (37.0 ± 0.5) ℃; The cropping of bilateral groin, sterilization with 2% lignocaine local anesthesia, separates respectively a side thigh artery and vein when cutting skin; Venous side is with the disposable venous infusion needle femoral vein that punctures, and be used for input antihypertensive drugs and fluid infusion: arterial side is put pipe with 24G arterial puncture needle puncture femoral artery, connects threeway and direct pressure measure switcher is directly surveyed arterial pressure.Behind blood pressure stabilization, the Glucose Liquid by 5% is mixed with the network that blood pressure lowering of the compound 1mg/ml Chinese mugwort of 0.2mg/ml sodium nitroprusside department, drops to the target blood pressure in 10~15min, by the adjusting pump speed that is interrupted, keeps the target blood pressure; The total amount infused (comprising the antihypertensive drugs amount of liquid) of all rats is 3.6ml between pressure reducing period, reduces the impact on blood volume as far as possible.After blood pressure lowering is complete, extracts the 0.5ml arterial blood from arterial side and carry out blood gas analysis, and mend the corresponding salt water yield; Pull out the arterial cannula pin, the artery-compression hemostasis, and pull out disposable venous infusion needle, and compressing, the corresponding stitching of muscle skin is guarded it and is revived.And giving the penicillin twice of 8U/kg in the 24h, the abdominal cavity subcutaneous injection is observed 24h.
Get 40 of successful surgery rats, be divided at random controlled hypotension group, compositions administration group 1, compositions administration group 2 and administration matched group, 10 every group.Other gets 10 of healthy rats as sham operated rats.Sham operated rats gives normal saline, the controlled hypotension group gives normal saline, compositions administration group 1 gives embodiment 4 compositionss, compositions administration group 2 gives embodiment 1 compositions, the administration matched group gives commercially available Radix Notoginseng total arasaponins product (arasaponin R1 8.0%, the ginsenoside Rg1 30%, the ginsenoside Rb1 31%, and the ginsenoside Re 2.5%, and the ginsenoside Rd 11%).After the administration 30 days, observe each treated animal feed, gait, righting reflex, behavioral function etc.
2, result
The functional evaluation of sham operated rats postoperative neuroethology shows no obvious abnormalities, and survival rate is 100%; Dull phenomenon appears in the controlled hypotension group, is slow in action, and to food and water bradykinesia, going down all appears in righting reflex and slope balanced capacity, and survival rate only is 36%; The administration matched group slightly is improved above-mentioned reaction, but not remarkable, and survival rate is 68%; Compositions administration group 1 and 2 can significantly be improved the neuroethology function assessment index, and righting reflex and slope equilibrium function recover normally substantially, and blood pressure recovers normally substantially, survival rate 100%.Show that this compositions can by regulating blood pressure, improve the brain injury function.
Experimental example 2 is on the impact of content of homocysteine
Select Patients with Cerebral Infarction 145 examples, be divided into two groups, pharmaceutical composition group man 40 examples, women 35 examples, 52.62 ± 7.66 years old mean age; Administration matched group man 38 examples, women 32 examples, 50.32 ± 6.93 years old mean age.Respectively at the empty stomach venous blood samples 2ml in morning next day that is admitted to hospital, detect homocysteine.Pharmaceutical composition group patient homocysteine amount average out to 22.48 ± 6.03, administration matched group patient homocysteine amount average out to 20.67 ± 5.44.Two groups of patients gave respectively embodiment 4 compositionss and commercially available product (arasaponin R1 8.0%, the ginsenoside Rg1 30%, the ginsenoside Rb1 31%, the ginsenoside Re 2.5%, the ginsenoside Rd 11%) 30 days.As a result, the total effective rate of pharmaceutical composition group is 86.33%, and the homocysteine amount is reduced to 15.47 ± 1.93, and reduction rate is 31%; The total effective rate of administration matched group is 80.74%, and the homocysteine amount is reduced to 16.55 ± 2.61, and reduction rate is 20%.Show, this pharmaceutical composition can effectively be treated apoplexy, and significantly reduces the homocysteine amount.
The inspections such as experimental example 3 undue toxicitys, anaphylaxis, acute toxicity
Choose embodiment 4 and carry out the following safety testing
1) acute toxicity test
Carry out with reference to " herbal pharmacology research methodology " acute toxicity test, adopt conventional prerun, measure maximum lethal dose and the minimum lethal dose of product abdominal cavity and tail vein injection, get 130 mices and be divided at random 13 groups, every group 10, male and female half and half are given the product solution of mouse tail vein and lumbar injection various dose, observe the poisoning symptom of mice, adopt the Sun Shi synthetic method to calculate the LD50 value.Found that, after administration in the different time, freely movable the minimizing appears in mice, when dying respiratory frequency speed, the poisoning symptoms such as mouth breathing, flaring of alaenasi.The LD50 of lumbar injection is 765.12mg/kg; The LD50 of tail vein injection is 450.34mg/kg.
2) hypersensitive test
With sodium chloride injection product is diluted for containing the solution of compositions 20mg among every 1ml, give guinea pig intraperitoneal injection.Each 0.5ml/ only, the next day once, totally three times.After the administration the 14th day and the 21st day respectively this solution of intravenous injection 1.0ml/ only, the result is showed no Cavia porcellus anaphylaxis.After giving Ovum Gallus domesticus album the 14th day and the 21st day of the Cavia porcellus that gives 5% fresh albumen anaphylaxis all occurring behind the intravenous injection Ovum Gallus domesticus album respectively, and all dead in 15min.These results show, the anaphylaxis of this product checks up to specification.
3) haemolysis and agglutination test
With reference to " appendix related content of Chinese pharmacopoeia version in 2010 is tested, and the result shows, this product in 3 hours to family's rabbit erythrocyte without haemolysis and red cell agglutination.
4) vascular stimulation test
Test with reference to " specification requirement of study of tcm new drug " related content, adopt the ear contrast of the consubstantiality left and right sides, get 3 rabbit, left ear is injected this product 5.0ml (25mg)/only by auricular vein, auris dextra waits the sodium chloride injection of capacity, once a day, and continuous three days.The result shows, the perusal of rabbit auricular vein medicine-feeding part is without significant change, and the pathological section microscope inspection shows, continuous, complete apart from injection site 1cm place blood vessel endothelium, have no hypertrophy, swelling, the blood vessel surrounding tissue has no inflammatory cell infiltration and downright bad phenomenon, and forms without thrombosis in the tube chamber.These results show, this product is without the blood vessel irritant reaction.
5) abnormal toxicity test
With reference to " appendix related content of Chinese pharmacopoeia version in 2010 is tested, this product solution of mouse tail vein injection 0.5ml (2.5mg)/only, and the result shows, dead and other Novel presentations all occur in 5 mices.
Above-mentioned result of the test shows, the application safety of this product is up to specification.
Although above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this is aobvious and Yi Fengjian to those skilled in the art.Therefore, this modification of this that make without departing from theon the basis of the spirit of the present invention or improvement all belong to the scope of protection of present invention.