CN1429830A - Water-soluble safflower extract and its oral preparation for treating and preventing angiocardiopathy andcerebrova scular disease - Google Patents
Water-soluble safflower extract and its oral preparation for treating and preventing angiocardiopathy andcerebrova scular disease Download PDFInfo
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Abstract
A water-soluble safflower extract, its oral-applied medicine for preventing and treating cardiovascular and cerebrovascular diseases, and their preparing process and disclosed. The content of hydrate safflower uranidin A and B are greater than 50%. Its advantages are high curative effect, and low toxic by-effect.
Description
The present invention relates to the water-soluble Flos Carthami extract and the oral preparations thereof of a kind of prevention, treatment cardiovascular and cerebrovascular diseases.
Cerebrovascular disease is harm humans life and healthy common disease and frequently-occurring disease, has sickness rate height, disability rate height, mortality ratio height and the high characteristics of recurrence rate, is the principal disease that the elderly causes death, disables.In the putting in order of the human various diseases cause of the death, cerebro-vascular diseases is positioned at the prostatitis always, becomes one of human main causes of death.In recent years, along with improving constantly of China's people's living standard, the aged increases, and the cerebrovascular disease sickness rate is ascendant trend year by year.
The history of the medicinal existing more than one thousand years of safflower." detailed outline " record, the safflower tool " is invigorated blood circulation, is moisturized ", " Xinxiu Bencao " record, safflower can " control trismus and inability to speak, blood knot ", " property of medicine is examined " record, safflower can " be given birth to the new broken stasis of blood ", controls in " mouth keep silent paralysis ".
China's chemical ingredients to safflower since the seventies has been carried out extensive studies, wherein mainly contain flavonoid, lignanoids, polyyne class etc., majority studies have shown that, the main effective constituent of safflower is present in its water soluble part, be the mixture of multiple water-soluble flavone compounds, have physiologically active promoting blood circulation and removing blood stasis.In recent years, domestic scholars is furtherd investigate the pharmacological action of safflower water soluble part, finds that it all has tangible pharmacological effect at aspects such as expanding hat, step-down, antithrombotic, anticoagulation, promoting blood circulation and removing blood stasis, hypoxia tolerance, immunosuppression.The safflower water soluble part has obvious suppression effect and unzipping to ADP inductive platelet aggregation, and rat is had blood coagulation resisting function preferably, and strengthens along with the increase of dosage, and the safflower water soluble part is to the restraining effect that is formed with highly significant of thrombus; The safflower water soluble part can influence panting perdurability after the cerebral ischemia anoxic.A large amount of pharmacological evaluation prove that the safflower water soluble part is one of important substance basis of safflower for treating cerebral thrombosis and sequela thereof.
Raw medicinal material safflower Carthamus tinctorius L. records in " 2 years versions of Pharmacopoeia of People's Republic of China " (one one).Modern times, safflower single preparation " Flos Carthami injection " recorded in national drug standards WS clinically
3-B-3825-98 is used for the treatment of obliterated cerebral vascular disease, coronary heart disease, and vasculitis etc., through clinical application for many years, its curative effect affirms that they are useful: 50% Flos Carthami injection 15ml (containing crude drug 75g) adds 10% glucose 500ml iv drip; 10% Flos Carthami injection 2ml adds 10% glucose 2ml hybrid injection and is used for the treatment of ischemic cerebrovascular, treatment cerebral arteriosclerosis, but this kind is traditional traditional Chinese medicine, mostly be crude extract, basic substance is indeterminate, and complicated component, the method that shortage control effectively to its quality because said preparation is the solution form, also is difficult to guarantee the stability of effective constituent wherein.
Though mostly domestic some relevant Flos Carthami extract patents that also disclose are the indefinite crude extract of some compositions, still exist same above-mentioned technological deficiency aspect medication.
Develop determined curative effect from traditional safflower Chinese medicine, toxic side effect is little, and is quality controllable, and safflower form of Chinese drug easy to use has feasibility and necessity.
The invention provides a kind of water-soluble Flos Carthami extract that contains hydration safflower yellow A and hydration safflower photopigment B, wherein hydration safflower yellow A and the weight percentage of hydration carthamin yellow carthamus B in this Flos Carthami extract are 50%-100%, and preferred weight percentage composition scope is: 65%-100%; Wherein, the ratio between hydration safflower yellow A and the hydration carthamin yellow carthamus B is 1 in this Flos Carthami extract: (0.1-2).
We have carried out deep research to the efficient part water soluble component of safflower on the basis of single safflower clinical application, extracted from dried floral and contained hydration safflower yellow A and the water-soluble Flos Carthami extract of hydration carthamin yellow carthamus B.
Extract of the present invention can obtain by conventional extracting method, also can adopt extracting method of the present invention, but preferably adopts extracting method of the present invention to obtain, and extracting method wherein of the present invention is:
Get dry safflower 60-100 ℃ and use water extraction 2-4 time down, water consumption is 10-30 times, and each time of extracting is 30-90 minute, it is 1.00-1.25 that merging filtrate, filtrate decompression are concentrated into density, and adding ethanol to determining alcohol is 60%-90%, precipitate 24 hours down in 4 ℃, filter; Filtrate is in 60 ℃ of decompression recycling ethanols, add to the low-pole macroporous adsorbent resin of handling well on 10 times of water dilution backs, applied sample amount (being equivalent to the crude drug amount) is 1 with the ratio of resin demand: (0.5-2) (w/v), wash 2-5 column volume with 20%-50% ethanol, collect elutriant.Elutriant is splined on the polyamide column of handling well, and the ratio that applied sample amount is equivalent to crude drug amount and resin demand is (2-4): 1 (w/v), with 2-4 column volume of 20%-50% ethanol elution, discards earlier; Continue to collect elutriant in 60 ℃ of decompression recycling ethanols, be drying to obtain with 3-5 column volume of 80%-95% ethanolic soln wash-out.
Present method the best is: get dry safflower, add water and extract 3 times down at 80 ℃, add 20 times for the first time and extracted under water 60 minutes, add 15 times of water extraction 60 minutes for the second time, add 15 times of water extraction 60 minutes for the third time, united extraction liquid; Extracting solution filters, and it is 1.05 (80 ℃) that filtrate decompression is concentrated into density, and adding ethanol to determining alcohol is 80%, precipitates 24 hours down in 4 ℃, filters; Filtrate adds to the DM-130 macroporous adsorbent resin of handling well on 10 times of water dilution backs in 60 ℃ of decompression recycling ethanols, and applied sample amount (being equivalent to the crude drug amount) is 1: 1 (w/v) with the ratio of resin demand, with 3 column volumes of 30% ethanol elution, collects elutriant.Elutriant is splined on the polyamide column of handling well, and the ratio that applied sample amount is equivalent to crude drug amount and resin demand is 2.8: 1 (w/v), earlier with 3 column volumes of 30% ethanol elution, discards; Continue with 4 column volumes of 95% ethanolic soln wash-out, collect elutriant, be drying to obtain in 60 ℃ of decompression recycling ethanols.
The oral pharmaceutical carrier of the extract of the present invention of effective dose and pharmaceutically acceptance can be made tablet, capsule, granule, wherein be preferably capsule and granule.
When making capsule, the weight percent of Flos Carthami extract of the present invention in pharmaceutical capsules should be: 2%-80%, all the other are weighting agent, 70% ethanolic soln and an amount of orange essence.
Prescription that capsule medicine of the present invention is concrete and preparation method are:
Flos Carthami extract 50g, starch 100g, dextrin 50g, 90% ethanolic soln is an amount of, micropowder silica gel is an amount of.
The Flos Carthami extract, starch, the dextrin that take by weighing recipe quantity are crossed twice of 80 mesh sieve mixing, add the mixed softwood of 90% ethanolic soln, softwood is agglomerating to hold, the pressure break that press...withes one's finger is opened to good, cross 24 mesh sieves extruding system wet granular, dry in 50 ℃ of air dry ovens, particle took out the whole grain of 20 mesh sieves when closely dried, continue to smoke for some time to doing, smoke approximately altogether about one hour, the particle of oven dry is weighed, add micropowder silica gel by 0.8% (W/W), fine powder in elder generation and the particle mixes, and adds in the particle to mix again, and particle is filled into capsule promptly.
When making granule, the weight percentage of extract of the present invention in granules medicine is 2%-68%, and all the other are weighting agent, an amount of 90% ethanolic soln and an amount of micropowder silica gel.
The concrete prescription and the preparation method of granules medicine of the present invention are:
Flos Carthami extract 100g, sucrose 1000g, lactose 400g, citric acid 7.5g, 70% ethanolic soln is an amount of, orange essence is an amount of.
Sucrose was pulverized 80 mesh sieves, sucrose and lactose were put into 60 ℃ of baking ovens dry 3 hours, the sucrose and the lactose that take by weighing recipe quantity are crossed twice of 80 mesh sieve mixing, add Flos Carthami extract by the equivalent multiplication method then, mix, citric acid is dissolved in part 70% ethanolic soln, add in the pressed powder and make softwood, looking the wet degree of doing of softwood drinks and adds an amount of 70% ethanol and make suitable softwood, cross 16 mesh sieves extruding system wet granular, dry in 50 ℃ of air dry ovens, particle took out the whole grain of 14 mesh sieves when closely dried, continue to smoke for some time to doing, smoke about one hour the particulate classification altogether approximately: the particle of oven dry is crossed a sieve and No. four sieves respectively, discard coarse particles that can not pass through a sieve and the fine powder that passes through No. four sieves, spray essence: particle places in the coating pan and rolls, and mandarin oil essence is dissolved in (1%) in the dehydrated alcohol, by spray gun it is sprayed into.Then particle is put into encloses container, seal 12 hours, packing, promptly.
The pharmacological toxicology result of study shows that extract oral administration of the present invention is compared with existing safflower drug extract in the body and absorbed well, can obviously reduce arteria cerebri media embolism model cerebral ischemia district necrosis area, suppresses the formation of external thrombus, prolongs the clotting time; Toxicological experiment shows that Flos Carthami extract is evident in efficacy, toxic side effect is little; Basic substance of the present invention in addition is clear and definite, effective constituent is stable and controllable for quality and easy administration, good absorption.
The preparation of safflower water soluble extract
Embodiment 1
Get dry safflower, add water and extract 3 times down, add 20 times for the first time and extracted under water 60 minutes, add 15 times of water extraction 60 minutes for the second time, add 15 times of water extraction 60 minutes for the third time, united extraction liquid at 80 ℃; Extracting solution filters, and it is 1.05 (80 ℃) that filtrate decompression is concentrated into density, and adding ethanol to determining alcohol is 80%, precipitates 24 hours down in 4 ℃, filters; Filtrate adds to the DM-130 macroporous adsorbent resin of handling well on 10 times of water dilution backs in 60 ℃ of decompression recycling ethanols, and applied sample amount (being equivalent to the crude drug amount) is 1: 1 (w/v) with the ratio of resin demand, with 3 column volumes of 30% ethanol elution, collects elutriant.Elutriant is splined on the polyamide column of handling well, and the ratio that applied sample amount is equivalent to crude drug amount and resin demand is 2.8: 1 (w/v), earlier with 3 column volumes of 30% ethanol elution, discards; Continue with 4 column volumes of 95% ethanolic soln wash-out, collect elutriant, be drying to obtain, measure in 60 ℃ of decompression recycling ethanols.
Embodiment 2
Get dry safflower, add water and extract 2 times down, add 20 times for the first time and extracted under water 60 minutes, add 15 times of water extraction 60 minutes for the second time, add 15 times of water extraction 60 minutes for the third time, united extraction liquid at 70 ℃; Extracting solution filters, and it is 1.00 (80 ℃) that filtrate decompression is concentrated into density, and adding ethanol to determining alcohol is 60%, precipitates 24 hours down in 4 ℃, filters; Filtrate adds to the DM-130 macroporous adsorbent resin of handling well on 10 times of water dilution backs in 60 ℃ of decompression recycling ethanols, and applied sample amount (being equivalent to the crude drug amount) is 1: 0.8 (w/v) with the ratio of resin demand, with 2 column volumes of 25% ethanol elution, collects elutriant.Elutriant is splined on the polyamide column of handling well, and the ratio that applied sample amount is equivalent to crude drug amount and resin demand is 2: 1 (w/v), earlier with 2 column volumes of 25% ethanol elution, discards; Continue with 3 column volumes of 80% ethanolic soln wash-out, collect elutriant, be drying to obtain, measure in 60 ℃ of decompression recycling ethanols.
Embodiment 3
Get dry safflower, add water and extract 4 times down, add 20 times for the first time and extracted under water 60 minutes, add 15 times of water extraction 60 minutes for the second time, add 15 times of water extraction 60 minutes for the third time, united extraction liquid at 90 ℃; Extracting solution filters, and it is 1.20 (80 ℃) that filtrate decompression is concentrated into density, and adding ethanol to determining alcohol is 90%, precipitates 24 hours down in 4 ℃, filters; Filtrate adds to the DM-130 macroporous adsorbent resin of handling well on 10 times of water dilution backs in 60 ℃ of decompression recycling ethanols, and applied sample amount (being equivalent to the crude drug amount) is 1: 2 (w/v) with the ratio of resin demand, with 4 column volumes of 40% ethanol elution, collects elutriant.Elutriant is splined on the polyamide column of handling well, and the ratio that applied sample amount is equivalent to crude drug amount and resin demand is 4: 1 (w/v), earlier with 4 column volumes of 30% ethanol elution, discards; Continue with 5 column volumes of 95% ethanolic soln wash-out, collect elutriant, be drying to obtain, measure in 60 ℃ of decompression recycling ethanols.
The preparation of oral preparations
The preparation of embodiment 4 granules
Flos Carthami extract 100g, sucrose 1000g, lactose 400g, citric acid 7.5g, 70% ethanolic soln is suitable, orange essence is an amount of, sucrose was pulverized 80 mesh sieves, sucrose and lactose were put into 60 ℃ of baking ovens dry 3 hours, the sucrose and the lactose that take by weighing recipe quantity are crossed twice of 80 mesh sieve mixing, add Flos Carthami extract by the equivalent multiplication method then, mix, citric acid is dissolved in part 70% ethanolic soln, add in the pressed powder and make softwood, looking the wet degree of doing of softwood drinks and adds an amount of 70% ethanol and make suitable softwood, cross 16 mesh sieves extruding system wet granular, dry in 50 ℃ of air dry ovens, particle took out the whole grain of 14 mesh sieves when closely dried, continued to smoke for some time to doing, smoke about one hour altogether approximately, the particulate classification: the particle of oven dry is crossed a sieve and No. four sieves respectively, discard can not be by a sieve coarse particles and the fine powder by No. four sieves, spray essence: particle places rolling in the coating pan, mandarin oil essence is dissolved in (1%) in the dehydrated alcohol, by spray gun it is sprayed into.Then particle is put into encloses container, seal 12 hours, packing, promptly.
The preparation of embodiment 5 capsules
Flos Carthami extract 50g, starch 100g, dextrin 50g, 90% ethanolic soln is an amount of, micropowder silica gel is an amount of; The Flos Carthami extract, starch, the dextrin that take by weighing recipe quantity are crossed twice of 80 mesh sieve mixing, add the mixed softwood of 90% ethanolic soln, softwood is agglomerating to hold, the pressure break that press...withes one's finger is opened to good, cross 24 mesh sieves extruding system wet granular, dry in 50 ℃ of air dry ovens, particle took out the whole grain of 20 mesh sieves when closely dried, continue to smoke for some time to doing, smoke approximately altogether about one hour, the particle of oven dry is weighed, add micropowder silica gel by 0.8% (W/W), fine powder in elder generation and the particle mixes, and adds in the particle to mix again, and particle is filled into capsule promptly.
Experimental example 1. Flos Carthami extract capsules are to the influence of rat local cerebral ischemia damage
1.1 material
Given the test agent: the Flos Carthami extract capsule, press embodiment 5 preparations.Specification: 200mg (containing Flos Carthami extract raw material 50mg)/grain faces the solution that is mixed with desired concn with physiological saline with preceding.
Positive control drug: nimodipine tablet, Sino-Japan joint Hebei Dong Long pharmaceutcal corporation, Ltd, specification: the 25mg/ sheet, lot number: 000703, authentication code: the accurate word (1995) of medicine is defended No. 040128 in the Ji, with the preceding suspension that is made into 1.8mg/ml with physiological saline.
Positive control drug: the NAODESHENG chewable tablet, Shandong Green Leaf Pharmaceutical Co., Ltd, specification: the 1.1g/ sheet, lot number: 20010426, authentication code: the accurate word Z20000073 of traditional Chinese medicines, with the preceding suspension that is made into 125mg/ml with physiological saline.TCC: U.S. Sigma company product, face with preceding and be made into 4% solution with physiological saline.Digital camera: Olympus company
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, Shandong Green Leaf Pharmaceutical Co., Ltd's Experimental Animal Center provides, conformity certification number: No. 200106005, Shandong kinoplaszm word.
1.2 method and result
Animal is divided into sham operated rats (i.g.NS) at random, model control group (i.g. physiological saline), nimodipine group (i.g.Nim, 12mg/kg), the NAODESHENG group (i.g.NDS, 1g/kg), SF small dose group (i.g.SF, 10mg/kg), dosage group among the SF (i.g.SF, 20mg/kg), the heavy dose of group of SF (i.g.SF, 40mg/kg), 10 every group.After the fasting 12 hours, each treated animal is irritated the stomach relative medicine respectively, administration volume 1ml/100g.After 2 hours, and Chloral Hydrate (350mg/kg, i.p.) anesthesia separates left carotid, and folder closes in the neck, arteria carotis communis, external carotid artery proximal part and distal end ligation, cut off the centre.The external carotid artery free end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire for use, length 5.0cm) is inserted into encephalic by external carotid artery, stop when meeting slight resistance, depth of penetration is about 2cm.Ligation external carotid artery opening, and open the arteria carotis communis bulldog clamp, the disinfection and stitching wound causes left side arteria cerebri media ischemia model; Sham operated rats is only carried out the separation (above experiment is all carried out at 23 ℃～25 ℃) of left carotid, internal carotid artery, external carotid artery.Observe and write down the behavior disorder of rat by literature method and standard after 24 hours: (1) is carried the mouse tail and is observed forelimb flexing situation, stretch to ground as two forelimb symmetries, count 0 fen, as the offside forelimb of performing the operation the wrist flexing occurs and counts 1 fen, the elbow flexing is counted 2 fens, and the shoulder inward turning is counted 3 fens, existing wrist flexing and/or elbow flexing, shoulder inward turning person is arranged again, count 4 fens.(2) animal is placed on the plane earth, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, count 0 fen, as resistance descender when the operation offside promotes, according to decline degree difference be divided into gently, in, weigh three degree, count 1,2 and 3 fen respectively.(3) the two forelimbs of animal are put on the wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 fen.Count 1,2 and 3 fen according to operation offside muscular tension decline degree difference equally.(4) animal has ceaselessly to a side person of turn-taking, and counts 1 fen.According to the standard scoring, full marks are 11 minutes, and mark is high more, and expression animal behavior obstacle is serious more.Put to death rat behind the behavior scoring, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, the brain sheet takes on a red color after healthy tissues is dyed with TCC (TTC) dyeing, and blocking tissue is white in color, taking a picture in dyeing back, asks the infarct size ratio with Chinese aerospace university pathological image analysis software.Data are represented with X ± S, carry out statistical procedures with t check between group.
The result shows that ischemic is after 24 hours, and rat shows tangible behavior disorder, and tangible kitchen range shape ischemic region also appears in rat cerebral tissue, reaches about 25% of full brain; Give the SF of various dose, the animal behavior obstacle has alleviating in various degree, and the rat cerebral ischemia district also takes an evident turn for the better, and is dose-dependently (table 1).
The influence that table 1 flower extract capsule damages the rat local cerebral ischemia (n=10, X ± S)
Group behavior disorder ischemic areas (%)
Sham operated rats 00
Model control group 10.10 ± 1.37 24.26 ± 4.13
NDS group 7.30 ± 2.67
*19.90 ± 3.02
*
Nim group 6.90 ± 2.33
*13.09 ± 7.11
*
The heavy dose of group 7.20 ± 1.93 of SF
*12.27 ± 4.73
*
Dosage group 7.50 ± 3.03 among the SF
*18.41 ± 2.84
*
SF small dose group 8.80 ± 2.44
△21.06 ± 3.20
△
Compare with model control group
*P＜0.05,
*P＜0.01,
△P＞0.05.1.3 conclusion: the Flos Carthami extract capsule can obviously improve the behavior disorder of rats with cerebral ischemia, dwindles the ischemic region scope, and ischemic brain injury is had significant protective effect.
The influence that test example 2. Flos Carthami extract capsules form the rat thrombus in vivo
2.1 material
Given the test agent: the Flos Carthami extract capsule, by the embodiment of the invention 5 preparations.Specification: 200mg (containing Flos Carthami extract raw material 50mg)/grain faces the solution that is mixed with desired concn with physiological saline with preceding.
Positive control drug: the NAODESHENG chewable tablet, Shandong Green Leaf Pharmaceutical Co., Ltd, the 1.1g/ sheet, lot number: 20010426, authentication code: the accurate word Z20000073 of traditional Chinese medicines, with the preceding suspension that is made into 125mg/ml with physiological saline.
Regular grade Wistar rat, male, body weight 230g～250g, Shandong Green Leaf Pharmaceutical Co., Ltd's Experimental Animal Center provides, conformity certification number: No. 200106005, Shandong kinoplaszm word.
2.2 method and result
2.2.1 to moving-thrombotic influence of vein bypass
[3]Animal is divided into blank group (i.g. physiological saline) at random, NAODESHENG group (i.g.1g/kg), SF small dose group (i.g.SF 10mg/kg), dosage group among the SF (i.g.SF 20mg/kg), the heavy dose of group of SF (i.g.SF 40mg/kg), 10 every group.After the fasting 12 hours, each treated animal is irritated the stomach relative medicine respectively, and after 2 hours, (350mg/kg i.p.), separates right carotid and left external jugular vein to chloral hydrate anesthesia, puts into No. seven silk threads that a long 5cm has weighed in polyethylene tube.Be full of polyethylene tube with the normal saline solution that contains heparin sodium (50U/ml), an end of polyethylene tube inserts left external jugular vein, and the other end inserts right common carotid artery.Open folder and close the bulldog clamp of blood vessel, make blood flow flow through polyethylene tube from right general neck artery after, return left external jugular vein.Take out silk thread behind the open blood flow 15min rapidly and weigh, deduct silk thread weight and promptly get wet weight of thrombus.Data represent that with X ± S statistical procedures is carried out in the t check between group.The result shows that NDS group, the big or middle dosage group of SF thrombus weight are starkly lower than blank group (table 2).
Table 2 Flos Carthami extract capsule to rat moving-the thrombotic influence of vein bypass (X ± S)
Group wet weight of thrombus inhibiting rate (%)
Blank group 26.09 ± 4.21
NDS group 15.43 ± 5.15
*40.86
The heavy dose of group 13.01 ± 6.81 of SF
*50.13
Dosage group 16.25 ± 3.91 among the SF
*37.72
SF small dose group 20.51 ± 9.79
△21.38 compare with the blank group
*P＜0.05,
*P＜0.01;
△P＞0.05.
2.2.2 to the thrombotic influence of rat vein
Animal is divided into blank group (i.g. physiological saline) at random, NAODESHENG group (i.g.NDS 1g/kg), SF small dose group (i.g.SF 10mg/kg), dosage group among the SF (i.g.SF 20mg/kg), the heavy dose of group of SF (i.g.SF40mg/kg), 10 every group.After the fasting 12 hours, each treated animal is irritated the stomach relative medicine respectively, and after 2 hours, Chloral Hydrate (open abdomen and separate postcava, with cordonnet ligation postcava, sews up belly in the left renal vein below by 350mg/kg, i.p.) anesthesia.Again open abdomen after 6 hours, 2cm place folder closes blood vessel below ligation place, cuts tube chamber open, and removal of thromboses is weighed.Data represent that with X ± S statistical procedures is carried out in the t check between group.The result shows: NDS group, the big or middle dosage group of SF thrombus weight are starkly lower than blank group (table 3).
Table 3 Flos Carthami extract capsule is to the thrombotic influence of rat vein (X ± S)
Group wet weight of thrombus inhibiting rate (%)
Blank group 29.91 ± 17.16
NDS group 14.01 ± 5.76
*53.16
The heavy dose of group 9.17 ± 6.65 of SF
*71.48
Dosage group 15.77 ± 4.26 among the SF
*47.29
SF small dose group 23.36 ± 11.20
△21.90
Compare with the blank group
*P＜0.05,
*P＜0.01;
△P＞0.05.
2.3 conclusion: the Flos Carthami extract capsule is moving-vein bypass thrombus and venothrombotic formation in the dose-dependent inhibition rat body.
Test example 3. Flos Carthami extract capsules are to the influence of clotting time of mice
3.1 material
Given the test agent: the Flos Carthami extract capsule, Shandong Province's natural drug Engineering Technical Research Centre provides, and is for orange-yellow powder, soluble in water.Lot number: 20010329, specification: 200mg (containing Flos Carthami extract raw material 50mg)/grain faces the solution that is mixed with desired concn with physiological saline with preceding.
Positive control drug: the NAODESHENG chewable tablet, Shandong Green Leaf Pharmaceutical Co., Ltd, the 1.1g/ sheet, lot number: 20010426, authentication code: the accurate word Z20000073 of traditional Chinese medicines; Be made into the suspension cleaning level level Kunming mouse of 100mg/ml with preceding with physiological saline, male, body weight 18.g～22g, Shandong Green Leaf Pharmaceutical Co., Ltd's Experimental Animal Center provides, conformity certification number: No. 200106003, Shandong kinoplaszm word.
3.2 method and result
60 of Kunming mouses are divided into blank group (i.g. physiological saline) at random, NAODESHENG group (2g/kg), SF small dose group (i.g.SF 20mg/kg), dosage group among the SF (i.g.SF 40mg/kg), the heavy dose of group of SF (i.g.SF 80mg/kg), 12 every group.After the fasting 12 hours, each treated animal is irritated the stomach relative medicine respectively, administration volume: 2ml/100g; After 2 hours, eye socket is got blood, measures the clotting time with slide method.Data represent that with X ± S statistical procedures is carried out in the t check between group.
The result shows: the big or middle dosage group clotting time of Flos Carthami extract capsule obviously is longer than blank group (table 4).
Table 4 Flos Carthami extract capsule is to the influence of clotting time of mice (X ± S)
The group clotting time
Blank group 67.00 ± 21.21
NDS group 89.17 ± 17.43
*
The heavy dose of group 112.75 ± 42.03 of SF
*
Dosage group 94.08 ± 35.68 among the SF
*
SF small dose group 81.92 ± 24.84
△
Compare with the blank group
*P＜0.05,
*P＜0.01;
△P＞0.05.
3.3 conclusion: the Flos Carthami extract capsule obviously prolongs clotting time of mice, and is dose-dependently.
Test example 4. Flos Carthami extract capsules are to the influence of rat blood rheological
4.1 material
Given the test agent: the Flos Carthami extract capsule, Shandong Province's natural drug Engineering Technical Research Centre provides, and is for orange-yellow powder, soluble in water.Lot number: 20010329, specification: 200mg (containing Flos Carthami extract raw material 50mg)/grain faces the solution that is mixed with desired concn with physiological saline with preceding.
Positive control drug: the NAODESHENG chewable tablet, Shandong Green Leaf Pharmaceutical Co., Ltd, the 1.1g/ sheet, lot number: 20010426, authentication code: the accurate word Z20000073 of traditional Chinese medicines, with the preceding suspension that is made into 125mg/ml with physiological saline.
Regular grade wistar rat, male, body weight 350～430g, Shandong Green Leaf Pharmaceutical Co., Ltd's Experimental Animal Center provides, conformity certification number: No. 200106005, Shandong kinoplaszm word.LBY-N6A hemorheology tester: Beijing Puli gives birth to company's product.
4.2 method and result
Animal is divided into blank group (i.g. physiological saline) at random, NAODESHENG group (i.g.NDS 1g/kg), SF small dose group (i.g.SF 10mg/kg), dosage group among the SF (i.g.SF 20mg/kg), the heavy dose of group of SF (i.g.SF40mg/kg), 10 every group.After the fasting 12 hours, each treated animal is irritated the stomach relative medicine respectively, and after 2 hours, (350mg/kg, i.p.) heart blood sampling 5ml/ only with 0.5% anticoagulant heparin, measures indexs such as whole blood viscosity, plasma viscosity to chloral hydrate anesthesia with the hemorheology tester.Data represent that with X ± S statistical procedures is carried out in the t check between group.
The result shows that the big or middle dosage of Flos Carthami extract capsule all can reduce rat whole blood viscosity, plasma viscosity and pcv (table 5).
Table 5 Flos Carthami extract capsule is to the influence of hemorheology of rat (X ± S)
Whole blood viscosity (mPa.s) plasma viscosity pcv
Group
(%) blank group 5.19 ± 0.47 6.38 ± 0.59 13.45 ± 1.05 1.60 ± 0.20 0.53 ± 0.05 NAODESHENG group 4.33 ± 0.20 of the high shear rate of shear rate (mPa.s) in the low shear rate
*5.31 ± 0.26
*11.52 ± 0.53
*1.43 ± 0.03
*0.47 ± 0.06
*The heavy dose of group 4.31 ± 0.46 of SF
*5.27 ± 0.58
*11.45 ± 1.09
*1.46 ± 0.04
*0.46 ± 0.04
*Dosage group 4.55 ± 0.57 among the SF
*5.58 ± 0.73
*12.10 ± 1.47
*1.40 ± 0.20
*0.53 ± 0.06
△SF small dose group 4.93 ± 0.38
△6.05 ± 0.47
△12.90 ± 0.80
△1.46 ± 0.15
△0.52 ± 0.05
△
Compare with the blank group
*P＜0.05,
*P＜0.01,
△P＞0.05.
Conclusion: the Flos Carthami extract capsule can reduce rat whole blood viscosity, plasma viscosity and pcv.
Test example 5,
1 material
Medicine: the Flos Carthami extract capsule, press embodiment 5 preparations, specification: 200mg (containing Flos Carthami extract 50mg)/grain.Face the solution that is mixed with desired concn with physiological saline with preceding.
Animal: a cleaning level Kunming mouse, male, body weight 18.g～22g, male and female half and half, Shandong Green Leaf Pharmaceutical Co., Ltd's Experimental Animal Center provides, conformity certification number: No. 200106003, Shandong kinoplaszm word.The Wistar rat, 170-200g, male and female half and half are provided by Shandong Province's natural drug Engineering Technical Research Centre Experimental Animal Center, conformity certification number: No. 200106005, the moving word in Shandong.
Instrument: tension pick-up (JZ100 type), pressure transmitter (YP200 type) are Gaobeidian City, Hebei mechanical ﹠ electronic equipment corporation, Ltd of newly navigating and produce.The PowerLab polygraph, Australian ADI-Instrument company produces.The single track electrocardiograph, FX-2111 type, Feitian, Beijing electronic medical instruments company limited.
2 methods and result
2.1 the Flos Carthami extract capsule is to the influence of mouse general behavior
Get 40 of mouse, be divided into 4 groups at random by body weight, 10 every group, male and female half and half, blank group (giving physiological saline), Flos Carthami extract capsule height (160mg/kg), in (80mg/kg), low (40mg/kg) dosage group, gastric infusion.The administration volume is the 0.4ml/20g body weight, and the general behavior of observing mouse after the administration immediately to 2 hours changes
[1]
The result shows: high, medium and low 3 dosage of Flos Carthami extract capsule do not have obvious influence to mouse auricular concha blood vessel and hair color, acorea enlarges and dwindles, there is not perpendicular hair, no palpebral fissure increases or dwindles phenomenon, gait, muscular strength are normal, no righting reflex loss phenomenon illustrates that the Flos Carthami extract capsule does not have influence to the mouse general behavior.
2.2 the Flos Carthami extract capsule is pressed document to the influence of mouse coordination of function
[1]Method improves slightly, mouse is placed on the smooth plate that becomes 70 ° of angles with horizontal plane, and mouse is screened, and gets and does not fall 40 of mouse, is divided into 4 groups at random by body weight, and grouping and administration are the same.Gastric infusion is observed the rate of falling (to put continuously 3 times, it is positive to fall 2 persons) of respectively organizing mouse respectively at 30min, 60min, 90min, 120min, 150min, 180min after the administration, and is carried out x with negative control group
2Check is (table 6) relatively.
Table 6 Flos Carthami extract capsule to influence (n=10) the group dosage 0min administration of mouse coordination of function after different time fall rate (%)
(mg/kg) capacity 0000000 chlorpromazine 10 0 80 such as 30min 60min 90min 120min 150min 180min physiological saline
*90
*100
*70
*70
*40
160 0000000 safflowers, 80 0000000 extracts 40 0000000
*P＜0.05,
*Compare with the physiological saline group P＜0.01
The result shows: the chlorpromazine group mouse has significantly between 30min-150min and falls, and high, medium and low 3 the dosage group mouse of Flos Carthami extract capsule fall rate and are zero, illustrate that the Flos Carthami extract capsule does not have influence to the mouse coordination of function.
2.3 the Flos Carthami extract capsule is to the synergy of mouse sub-threshold dose vetanarcol
Get 40 of mouse, be divided into 4 groups at random by body weight, male and female half and half, negative control group (waiting capacity physiological saline), Flos Carthami extract capsule height (160mg/kg), in (80mg/kg), low (40mg/kg) three dosage groups, 2 hours abdominal injection vetanarcol 30mg/kg behind the gastric infusion are the sleep index with the righting reflex loss, observe the sleep mouse number (righting reflex loss reach 1min above person positive) of each group in injection vetanarcol 30min, and carry out X with negative control group
2Check (table 7).
Table 7 Flos Carthami extract capsule is to the synergy (n=10) of mouse sub-threshold dose vetanarcol
Group dosage (mg/kg) sleep mouse number (only)
Physiological saline--0
160 0
Flos Carthami extract capsule 80 0
40 0
The result shows: the phenomenon of sleeping does not appear in the mouse of high, medium and low 3 the dosage groups of Flos Carthami extract capsule, the no significant difference of comparing with negative control group; Illustrate that Flos Carthami extract capsule and mouse sub-threshold dose vetanarcol do not have synergy.
2.4 Flos Carthami extract is got 40 of rats to the influence of anesthetized rat cardiovascular systems and respiratory system, male and female half and half, be divided into 4 groups at random, every group 10, be respectively blank group (giving physiological saline), Flos Carthami extract height (80mg/kg), in (40mg/kg), low (20mg/kg) 3 dosage groups.The medicine physiological saline solution, the administration volume is 1ml/kg.Animal is weighed, and irritates stomach, abdominal injection 20% urethane anesthesia (1.2g/kg).Separate a side arteria carotis communis, make the artery intubate, the other end of arterial cannulation is connected on the pressure transmitter that T-valve is housed, pressure signal is through transmitter input PowerLab polygraph.The right fore, left lower extremity and the right lower extremity that needle electrode are inserted animal respectively are subcutaneous, and electrocardiosignal is imported the FX-2111 electrocardiograph.At the xiphoid-process threading and be connected in tension pick-up, with the thorax tension signal by transmitter input PowerLab polygraph.Mean arterial pressure (MAP), systolic pressure (SAP), diastolic pressure (DAP), P-P (s), P-R (s), QRS (s), Q-T (s), T, respiratory rate and amplitude of respiration respectively at 10min, 20min, 30min, 60min, 120,180min record anesthetized rat after the administration.Experimental data represents that with X ± S each group and a blank T that organizes check.
The result shows: compare with the blank group, (80mg/kg, 40mg/kg 20mg/kg) all do not have obvious influence to anesthetized rat mean arterial pressure, systolic pressure and diastolic pressure, heart rate, electrocardio and respiratory rate and amplitude of respiration to the Flos Carthami extract capsule; Illustrate that the Flos Carthami extract capsule does not have influence to anesthetized rat cardiovascular systems and respiratory system;
3 conclusion (of pressure testing)s: Flos Carthami extract capsule 160mg/kg, 80mg/kg, 40mg/kg (suitable raw material dose) gastric infusion does not have obvious influence to general behavior and the coordinated movement of mouse, mouse peritoneal injection sub-threshold dose vetanarcol are not had synergy, show that high, medium and low 3 dosage of this medicine do not have obvious influence to mouse spirit neural system.Cardiovascular and respiratory system does not have obvious influence to anesthetized rat for Flos Carthami extract capsule 80mg/kg, 40mg/kg, 20mg/kg gastric infusion.
Claims (12)
1, a kind of water-soluble Flos Carthami extract for the treatment of cardiovascular and cerebrovascular diseases is characterized by that to contain weight percentage in this extract be 50%-100% safflower yellow A and Flos Carthami yellow pigment B.
2, will book 1 described Flos Carthami extract according to right, it is characterized by that to contain weight percentage in this extract be 65%-100% safflower yellow A and Flos Carthami yellow pigment B.
3, will book 1 or 2 described Flos Carthami extracts according to right, it is characterized by this and carry safflower yellow A in the thing: carthamin yellow carthamus B=1: 0.1-2.
4, extract 2-4 time under Flos Carthami extract according to claim 1 is got dry safflower 60-100 ℃, each time of extracting is 30-90 minute, merging filtrate, it is 1.00-1.25 that filtrate decompression is concentrated into density, adding ethanol to determining alcohol is 60%-90%, precipitates 24 hours down in 4 ℃, filters; Filtrate is in 60 ℃ of decompression recycling ethanols, add to the low-pole macroporous adsorbent resin of handling well on 10 times of water dilution backs, applied sample amount (being equivalent to the crude drug amount) is 1 with the ratio of resin demand: (0.5-2) (w/v), wash 2-5 column volume with 20%-50% ethanol, collect elutriant.Elutriant is splined on the polyamide column of handling well, and the ratio that applied sample amount is equivalent to crude drug amount and resin demand is (2-4): 1 (w/v), with 2-4 column volume of 20%-50% ethanol elution, discards earlier; Continue to collect elutriant in 60 ℃ of decompression recycling ethanols, be drying to obtain with 3-5 column volume of 80%-95% ethanolic soln wash-out
5, Flos Carthami extract according to claim 4, it is characterized by this extract obtains by the following method: get dry safflower, adding water extracts 3 times down at 80 ℃, for the first time adding 20 times extracted 60 minutes under water, add for the second time 15 times of water extraction 60 minutes, add 15 times of water extraction 60 minutes for the third time, united extraction liquid; Extracting solution filters, and it is 1.05 (80 ℃) that filtrate decompression is concentrated into density, and adding ethanol to determining alcohol is 80%, precipitates 24 hours down in 4 ℃, filters; Filtrate adds to the DM-130 macroporous adsorbent resin of handling well on 10 times of water dilution backs in 60 ℃ of decompression recycling ethanols, and applied sample amount (being equivalent to the crude drug amount) is 1: 1 (w/v) with the ratio of resin demand, with 3 column volumes of 30% ethanol elution, collects elutriant.Elutriant is splined on the polyamide column of handling well, and the ratio that applied sample amount is equivalent to crude drug amount and resin demand is 2.8: 1 (w/v), earlier with 3 column volumes of 30% ethanol elution, discards; Continue with 4 column volumes of 95% ethanolic soln wash-out, collect elutriant, be drying to obtain in 60 ℃ of decompression recycling ethanols.
5, contain the described Flos Carthami extract oral preparations of claim 1, it is characterized by tablet, capsule, granule.
6, according to the described oral preparations of claim 5, the formulation that it is characterized by this extract is capsule and granule.
7, oral preparations according to claim 6, wherein the weight percentage of this extract in this capsule medicine is 2%-80%, all the other are weighting agent and an amount of 70% ethanolic soln and orange essence.
8, oral preparations according to claim 7, wherein the prescription of this capsule and preparation method are: Flos Carthami total flavone 50g, starch 100g, dextrin 50g, 90% ethanolic soln is an amount of, micropowder silica gel is an amount of; The Flos Carthami total flavone, starch, the dextrin that take by weighing recipe quantity are crossed twice of 80 mesh sieve mixing, add the mixed softwood of 90% ethanolic soln, softwood is agglomerating to hold, the pressure break that press...withes one's finger is opened to good, cross 24 mesh sieves extruding system wet granular, dry in 50 ℃ of air dry ovens, particle took out the whole grain of 20 mesh sieves when closely dried, continue to smoke for some time to doing, smoke approximately altogether about one hour, the particle of oven dry is weighed, add micropowder silica gel by 0.8% (W/W), fine powder in elder generation and the particle mixes, and adds in the particle to mix again, and particle is filled into capsule promptly.
9, oral preparations according to claim 6, wherein the weight percentage of this extract in granules medicine is 2%-68%, all the other are weighting agent and an amount of 90% ethanolic soln and micropowder silica gel.
10, oral preparations according to claim 8, wherein the prescription of this granule and preparation method are: Flos Carthami total flavone 100g, sucrose 1000g, lactose 400g, citric acid 7.5g, 70% ethanolic soln is suitable, orange essence is an amount of, sucrose was pulverized 80 mesh sieves, sucrose and lactose were put into 60 ℃ of baking ovens dry 3 hours, the sucrose and the lactose that take by weighing recipe quantity are crossed twice of 80 mesh sieve mixing, add Flos Carthami total flavone by the equivalent multiplication method then, mix, citric acid is dissolved in part 70% ethanolic soln, add in the pressed powder and make softwood, looking the wet degree of doing of softwood drinks and adds an amount of 70% ethanol and make suitable softwood, cross 16 mesh sieves extruding system wet granular, dry in 50 ℃ of air dry ovens, particle took out the whole grain of 14 mesh sieves when closely dried, continue to smoke for some time to doing, smoke about one hour altogether approximately, particulate classification: the particle of oven dry is crossed a sieve and No. four sieves respectively, discard coarse particles that can not pass through a sieve and the fine powder that passes through No. four sieves, spray essence: particle places in the coating pan and rolls, mandarin oil essence is dissolved in (1%) in the dehydrated alcohol, by spray gun it is sprayed into.Then particle is put into encloses container, seal 12 hours, packing, promptly
11, a kind of pharmaceutical use that contains the described Flos Carthami extract of claim 1 is characterized by the pharmaceutical use for preparing treatment, prevention of arterial sclerosis, coronary heart disease, cerebral thrombosis, cerebral ischemia, stenocardia, myocardial infarction cardiovascular and cerebrovascular diseases.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01138665 CN1199979C (en) | 2001-12-29 | 2001-12-29 | Water-soluble safflower extract and its oral preparation for treating and preventing angiocardiopathy andcerebrova scular disease |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01138665 CN1199979C (en) | 2001-12-29 | 2001-12-29 | Water-soluble safflower extract and its oral preparation for treating and preventing angiocardiopathy andcerebrova scular disease |
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| Publication Number | Publication Date |
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| CN1429830A true CN1429830A (en) | 2003-07-16 |
| CN1199979C CN1199979C (en) | 2005-05-04 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1327846C (en) * | 2005-03-16 | 2007-07-25 | 郭东宇 | Sofflower injection and its prepn. method |
| CN100418522C (en) * | 2004-01-08 | 2008-09-17 | 山东瑞阳制药有限公司 | High-dose hydroxy safflower yellow A or its medically-acceptable salt application for preparing medicine for cerebral apoplexy induced from being ischemic |
| CN100450496C (en) * | 2004-12-14 | 2009-01-14 | 李捍雄 | Compound preparation of notoginseng and safflower for treating cardiovascular and cerebrovascular diseases |
| CN1813709B (en) * | 2005-01-31 | 2012-04-18 | 浙江永宁药业股份有限公司 | Safflower yellow dropping pill, and its preparing method and use |
| CN106189352A (en) * | 2016-07-19 | 2016-12-07 | 广州中大南沙科技创新产业园有限公司 | A kind of extracting method of Carthamus yellow |
-
2001
- 2001-12-29 CN CN 01138665 patent/CN1199979C/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100418522C (en) * | 2004-01-08 | 2008-09-17 | 山东瑞阳制药有限公司 | High-dose hydroxy safflower yellow A or its medically-acceptable salt application for preparing medicine for cerebral apoplexy induced from being ischemic |
| CN100450496C (en) * | 2004-12-14 | 2009-01-14 | 李捍雄 | Compound preparation of notoginseng and safflower for treating cardiovascular and cerebrovascular diseases |
| CN1813709B (en) * | 2005-01-31 | 2012-04-18 | 浙江永宁药业股份有限公司 | Safflower yellow dropping pill, and its preparing method and use |
| CN1327846C (en) * | 2005-03-16 | 2007-07-25 | 郭东宇 | Sofflower injection and its prepn. method |
| CN106189352A (en) * | 2016-07-19 | 2016-12-07 | 广州中大南沙科技创新产业园有限公司 | A kind of extracting method of Carthamus yellow |
| CN106189352B (en) * | 2016-07-19 | 2018-06-26 | 广州中大南沙科技创新产业园有限公司 | A kind of extracting method of carthamin yellow |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1199979C (en) | 2005-05-04 |
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