Summary of the invention
The objective of the invention is to: a kind of Chinese medicinal capsule agent and method for making and method of quality control of treating apoplexy is provided.
The present invention is achieved in that
One, prescription:
Radix Astragali 200g, reticulate millettia 100g, Radix Angelicae Sinensis 50g, Ligusticum wallichii 25g, bar branch 25g, hook Teng 25g, root of bidentate achyranthes 25g, safflower 25g, earthworm 75g, leech 75g, stiff silkworm 25g, scorpio 17g.
Two, method for making:
Leech, earthworm, stiff silkworm, scorpio are ground into fine powder; Radix Angelicae Sinensis, Ligusticum wallichii, cassia twig distillating extracting oil, the leaching distillate, device is preserved in addition, and the dregs of a decoction mix decoction the 2nd, 3 times with the decocting part; Boiling such as the Radix Astragali, safflower three times, each each 1.5 hours, three decocting liquids merged to filter and mix with above-mentioned distillate, and relative density is the clear cream of 1.25-1.30 when being evaporated to 65 ℃ of hot surveys, and 60 ℃ of forced air dryings are ground into fine powder; Get volatile oil and add the beta-schardinger dextrin-of its 3 times of amounts and the distilled water of 2 times of amounts, grind 40 minutes to pasty state, 50 ℃ of low temperature dryings are ground into fine powder, get above-mentioned fine powder and mix, and incapsulate, and process 1000.
Three, proterties:
The present invention is a capsule, and content is fallow powder, the little raw meat of gas, and it is little salty to distinguish the flavor of, little toil.
Four, differentiate:
(1) get the present invention, put microscopically and observe: mycelium is present in body wall or light brown, the translucent ingot, and mycelia is closely colourless, and is elongated, diameter 1-5 μ m, and travelling expenses interweave each other; The bristle yellowish-brown, how cataclasm, sharp point of tip or blunt circle, base portion is narrow slightly, and look light, stage casing diameter 4-8 μ m, tool is indulged straight grain, and pulp cavity is carefully narrow, and the chamber wall is more straight; The oblique muscle fiber is colourless, minority light brown, muscle fibre be prone to loose from or tangle each other, crooked or straight slightly mostly, diameter 4-36 μ m, the edge out-of-flatness, expand the part that has, light and dark line amount is not obvious; Elementary organization's cell is bigger, is similar round or class ellipse, and wall is thin, and is colourless, and single loosing left or several one-tenth agglomerates.
(2) get content 0.5g of the present invention, add water 10ml, jolting number minute was placed 30 minutes, filtered, and got an amount of drop of filtrating on filter paper, dried, and on spot, dripped ninhydrin solution, 105 ℃ of bakings several minutes, and spot is the basket purple.
(3) get content 1g of the present invention, put in the tool plug bottle, the 10ml that adds diethyl ether, jolting was placed 10 minutes, filtered, and filtrating is put in the evaporating dish and is volatilized, Dropwise 5 % vanillic aldehyde sulfuric acid solution on residue, the edge is purple.
(4) get content 4g of the present invention, add ethanol 30ml, water-bath reflux 40 minutes is put cold; Filter, get filtrating, add hydrochloric acid 3ml, the water-bath reflux is concentrated into about 5ml after 1 hour; Add water 10ml, put in the separating funnel, with the sherwood oil 30ml extraction of 60 ℃-90 ℃ of boiling points; Extract evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other evens up pier tartaric acid reference substance, adds ethanol and processes the solution that every 1ml contains 1mg, as reference substance solution; According to " each 10 μ l of above-mentioned two kinds of solution are drawn in the test of Chinese pharmacopoeia thin-layered chromatography, put respectively in same to contain on the silica gel H thin layer plate that sodium carboxymethyl cellulose is a bonding agent; With chloroform-ether=1: 1 was developping agent, launched, and took out; Dry, spray is with 5% phosphomolybdic acid ethanol test solution, and 110 ℃ were dried by the fire about 10 minutes; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(5) get content 6g of the present invention, put in the tool plug triangular flask, the 20ml that adds diethyl ether, close plug, cold soaking 30 minutes, jolting constantly filters, and filtrating volatilizes, and the residue 1ml that adds diethyl ether makes dissolving, as need testing solution; Other gets the cinnaldehydrum reference substance, adds ethanol and processes the solution that every 1ml contains 1 μ l, as reference substance solution; According to " test of Chinese pharmacopoeia thin-layered chromatography is drawn need testing solution 10 μ l, reference substance solution 2 μ l; Putting respectively on same silica gel g thin-layer plate, is developping agent with 60 ℃ of-90 ℃ of sherwood oil-ethyl acetates of boiling point=17: 3, launches; Take out, dry, spray is with dinitrophenylhydrazine ethanol test solution; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical orange red spot.
(6) get content 6g of the present invention, add methyl alcohol 30ml, put in the water-bath reflux 1 hour, filter, it is the 100-120 order that filtrating is added on the condition of having handled well; 5g on the neutral alumina post of internal diameter 10-15mm, with 40% methyl alcohol 100ml wash-out, collects eluent; Put evaporate to dryness in the water-bath, residue adds water 30ml makes dissolving, extracts 2 times with water saturated normal butyl alcohol, each 30ml; Merge normal butyl alcohol liquid, with water washing 2 times, each 30ml discards water liquid; Normal butyl alcohol liquid is put evaporate to dryness in the water-bath, and residue adds methyl alcohol 0.5ml makes dissolving, as need testing solution; Other gets the Astragaloside IV reference substance, adds methyl alcohol and processes the solution that every 1ml contains 1mg, as reference substance solution, according to " Chinese pharmacopoeia thin-layered chromatography test; Drawing each 10 μ l of above-mentioned two kinds of solution, put respectively in on-silica gel g thin-layer plate, is developping agent with lower floor's solution of chloroform-methanol-water=13: 7: 2, launches; Take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire about 5 minutes; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the sepia spot of same color.
Five, inspection: should meet " relevant each item regulation under the Chinese pharmacopoeia capsule item.
Six, assay:
Get 20 of the present invention, inclining content, accurate claim fixed after, porphyrize, precision takes by weighing the about 3g of content, put in the port grinding bottle, with water number drip moistening after, add normal butyl alcohol 20ml, refluxing extraction 2 hours; Filter while hot, filtrating is washed 3 times with 1%NaOH solution, and each 20ml discards alkali lye, and normal butyl alcohol liquid uses the saturated washing of normal butyl alcohol to neutral again; Tell n-butanol layer evaporate to dryness in water-bath, residue is with dissolve with methanol and be settled to 2ml, and as need testing solution, it is an amount of that precision takes by weighing the Astragaloside IV reference substance; Add methyl alcohol and process the solution that every ml contains 0.2mg, as reference substance solution, according to " reference substance solution 10 μ l are drawn in the test of Chinese pharmacopoeia thin-layered chromatography; Need testing solution 15 μ l put respectively on same-silica gel g thin-layer plate, so that chloroform-methanol-water=10 ℃ of lower floor's solution with held were developping agent in 6: 4: 1, launch; Take out, dry, spray was dried by the fire 5-7 minute down at 105 ℃ with the ethanolic solution of 10% sulfuric acid; Clear to the spot colour developing, take out, on thin layer plate, cover the glass plate of identical size, use immobilization with adhesive tape on every side; According to " the Chinese pharmacopoeia thin-layered chromatography scans, wavelength X S=530nm, and λ R=700nm measures test sample absorbance log integrated value and reference substance absorbance log integrated value, calculates, and it is C with Astragaloside IV, molecular formula that every of the present invention contains the Radix Astragali
44H
66O
4Meter must not be less than 0.01mg.
Seven, function and curing mainly:
Nourishing qi and blood, the phlegm that the dispels the wind network of invigorating blood circulation.Be applicable to the patient of the being seen qi deficiency to blood stasis disease of apoplexy apoplex involving the channels and collaterals, wind phlegm hemostasis numbness resistance channels disease; Be particularly useful for the convalescent, clinical manifestation is visible: not smoothgoing puckery, the disease such as dispute is crooked or have a dizzy spell or brothers' swelling or limbs Chinese holly contraction or limbs impotence be soft of hemiplegia, hemianesthesia, speech.
Eight, usage and dosage:
Oral, every 0.27g, a 4-6 grain, 3 times on the one.
Results of pharmacodynamic test: in order to further specify superiority of the present invention, product of the present invention has been carried out a series of pharmacodynamics test, test findings is summed up as follows:
L. capsule of the present invention is to the focal cerebral ischemia in rats influence of (acute stage)
Electrocoagulation blocking-up rat brain medium sized artery is adopted in this test; And ligation homonymy arteria carotis communis; Cause the focal cerebral ischemia model, observed the indexs such as nervous symptoms, cerebral infarction scope, Content of MDA, SOD activity and pathological examination of back acute stage are blocked in capsule for treating property administration of the present invention to the brain medium sized artery influence.The result shows: after causing the focal cerebral ischemia in rats model, and visible neurobehavioral obstacle, the crown section of brain is through the visible cerebral infarction kitchen range of TTC (chlorinated triphenyl tetrazole) dyeing; The 24h Content of MDA obviously increases; SOD is active obviously to be reduced, and the visible neurocyte of pathology light microscopy checking is downright bad, and endochylema thickens; Dyeing shoals, and interstitial edema is obvious.The animal via duodenum gives capsule of the present invention carry out the therapeutic administration after; The animal nerve symptom is obviously improved; Content of MDA obviously descends, and SOD is active obviously to be increased, and the cerebral infarction scope also has necessarily and reduces; The visible interstitial edema degree of pathological examination, the neurocyte degree of necrosis makes moderate progress than model group.Prompting: capsule of the present invention has the good curing effect to ishemic stroke (acute stage).
2. capsule of the present invention is to the focal cerebral ischemia in rats influence of (convalescence)
This experiment causes the focal cerebral ischemia in rats model with electrocoagulation blocking-up rat brain medium sized artery and ligation homonymy arteria carotis communis, and successive administration 7 days has been observed capsule of the present invention to the convalescent therapeutic action of this model.Test findings shows, cause the focal cerebral ischemia in rats model after, visible neurobehavioral obstacle; The obviously visible down cerebral infarction kitchen range (olistherozone) of mirror; Neurocyte is downright bad in the visible olistherozone of pathological examination, and karyon is thin narrow triangle or non-structure state, and kernel disappears.Give capsule of the present invention after 7 days, the animal nerve symptom has clear improvement, and the cerebral infarction scope obviously reduces, and the visible neurocyte degree of necrosis of pathological examination is obviously improved than model group.Prompting: the present invention has good therapeutic action to ishemic stroke convalescence.
3. capsule of the present invention is to the influence of rat experiment property cerebral ischemia
The total passages through which vital energy circulates of this experiment ligation rat bilateral cervical causes acute experiment property imperfection cerebral ischemic model, performs the operation preceding 2 hours each gastric infusion once in experiment the previous day at upper and lower noon and experiment; After the bilateral ligation 3 hours, broken end is opened cranium and is got brain; Claim weight in wet base, calculate cerebral index; Then in baking oven 100 ℃ dry to constant weight, survey dry weight and calculate brain water content.The ischemia model group is blue with each medication group 5min vena femoralis injection ivens before the total passages through which vital energy circulates of ligation bilateral cervical, and ligation is after 3 hours, and broken end is got brain and weighed; Immerse in the formamide solution respectively; Soaked 72 hours 45 ℃ of temperature, the pigment in the tissue is all leached, get soak solution with 721 spectrophotometer colorimetrics; Calculate the blue content of ivens in the brain tissue, thereby measure capillary permeability.The result shows that the present invention has the significant protection effect to rat experiment property cerebral ischemia, obviously improves pathological change such as cerebrovascular permeability and brain water content increase due to the cerebral ischemia.
4. capsule of the present invention is to the influence of anesthetized dog cerebral blood flow (CBF)
This experiment to the animal used as test Intravenous Anesthesia after, separate in the neck of left side, external carotid artery, the electromagnetic flowmeter probe is placed left side internal carotid, ligation external carotid artery.The ICAF amount of surveying, the variation of reflection cerebral blood flow (CBF), and calculate cerebral vascular resistance.Separate the left side femoral artery, intubate connects pressure transducer, surveys arterial pressure through carrier amplifier.Place cardiogram limbs crosslinking electrode, through ecg amplifier, the accurate II of mark mark leads cardiogram and calculates heart rate.All indexs all are recorded in polygraph.Execute abdominal operation, separate the duodenum stage casing, intubate is in order to giving institute's reagent thing.Operation finishes, treat that observed index is stable after, value before the record medicine feeds institute's reagent thing through duodenum, and behind medicine, carries out record in 5,10,15,20,30,45,60,90,120 minutes.After each item observation index carried out statistical procedures, carry out self relatively before the measured value of observing different time and the administration, its change percent organize between comparison, to judge its conspicuousness.The result shows: capsule of the present invention can significantly increase the anesthetized dog cerebral blood flow (CBF), reduces cerebral vascular resistance; Arterial pressure, heart rate, standard I I are led indexs such as cardiogram and do not have obvious influence.
5. capsule of the present invention is to the dissolution of rat artery thrombus
This experiment is with the electrode stimulating rat carotid artery, causes the blood vessel damage, causes platelet aggregation and forms thrombus.Through irritating the administration of stomach therapeutic, observe the present invention to thrombolytic effect.The result shows: the present invention has obvious dissolution to arterial thrombus.
6. capsule of the present invention is to the thrombotic influence of rat artery
This experiment separates the about 15mm of a side arteria carotis communis, and on artery, control group is 3min behind intravenous injection physiological saline or heparin with the stimulating electrode of experimental thrombus in vivo formation analyzer and temperature sensor hook; This experiment capsule is gastric infusion before experiment, once a day, and continuous 7 days; After the last administration 1 hour; With 1.5mA galvanic current stimulation vascular wall 7min, simultaneously by temperature sensor monitors blood vessel surface temperature variation, the record TFT.The result shows that capsule of the present invention has the effect that obviously delays TFT.
7. capsule of the present invention is to the thrombotic influence of rat artery-vein bypass
This animal used as test successive administration 4 days is in ip heparin on the 5th, after giving heparin 30min, behind this experiment administration group and positive control (Apoplexy Recover Pill) the group 60min; Get a special polyethylene catheter, one on built-in 5cm long filament line, the conduit two ends are inserted RCCA and left vena jugularis externa respectively; Blood carefully takes off conduit behind conduit circulation 15min, and the careful silk thread that takes out; Accurately weigh with analytical balance, and deduct the weight that silk thread was accurately weighed originally, be thrombus and weigh.The result shows that the present invention can obviously suppress rat suppository and form, and alleviates wet weight of thrombus, and the present invention has certain dose-effect relationship to the inhibiting effect that rat suppository forms.
8. capsule of the present invention is induced the influence of rat platelet aggregation to ADP
The rat oral gavage administration is given in this experiment, once a day, continuous use 15 days, 60min after the last medication, blood is got in docking.Every rat well-established law prepares platelet rich plasma (PRP) and platelet poor plasma (PPP), is 1.5 * 10 with (PPP) accent (PRP) to blood platelet
5Individual/mm
3, get each 200 μ l of PRP and PPP, place two respectively than turbid cup; Add 10 μ l physiological saline; Mix rearmounted 37 ℃ of insulation 2min, the PRP cup stirs the back zeroising, add respectively 5.0 μ lADP to ultimate density be 0.93 μ mol/L; Survey blood platelet MA (PA) with PAM-2 type platelet aggregation instrument, maximum coalescence rate (Vmax) and add ADP certainly and begin to 50% maximum gathering time (TE
50), and carry out comparing between each group.Experimental result shows that the present invention can obviously reduce platelet aggregation, prolongs the effect of platelet aggregation time.
9. capsule of the present invention is to the influence of clotting time of mice
Every mouse stomach administration of this experiment, continuous use are after 15 days, and behind last administration 60min, the eye socket bloodletting is surveyed the clotting time with the fragmentation method.The result shows that pharmaceutical capsules of the present invention can obviously prolong clotting time of mice.