CN100462082C - Erigeron breviscapus ketone ester and its injection preparation process - Google Patents
Erigeron breviscapus ketone ester and its injection preparation process Download PDFInfo
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- CN100462082C CN100462082C CNB2005100217692A CN200510021769A CN100462082C CN 100462082 C CN100462082 C CN 100462082C CN B2005100217692 A CNB2005100217692 A CN B2005100217692A CN 200510021769 A CN200510021769 A CN 200510021769A CN 100462082 C CN100462082 C CN 100462082C
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Abstract
The invention provides a process for extracting fleabane ketonic ester, the effective component of fleabane, and a process for preparing the fleabane ketonic ester injection. The fleabane ketonic ester comprises 50% of flavones and 40% of caffeic acid esters, and the extraction process consists of ethanol backflow abstraction, condensing, adjusting pH, alcohol deposition, concentrating supernatant fluid, passing through polyamide column, alcohol scrubbing, reclaiming the ethanol, mixing the obtained caffeic acid ester with three time total deposition, charging water for injection, adjusting pH, finally concentrating and drying. The injection comprises fleabane ketonic ester, medicinal auxiliary material and water for injection, and can be prepared into the forms of small injection, fluid infusion agent and freeze dried injection.
Description
Technical field:
The present invention relates to a kind of effective site erigeron breviscapus ketone ester that from the Herba Erigerontis medical material, extracts and the preparation method of injection thereof, belong to technical field of Chinese medicine, the present invention has the logical brain of the beneficial heart, blood circulation promoting and blood stasis dispelling, analgesic function, is mainly used in that the positive deficiency of vital energy of treatment declines, chest arthralgia precordial pain syndrome (angina pectoris), apoplexy (ischemia apoplexy and apoplexy sequela) due to the resistance of blood stasis arteries and veins.
Background technology:
The chest arthralgia precordial pain syndrome of theory of Chinese medical science indication, card is seen feeling of oppression and pain in the chest, shortness of breath and palpitation, weak sluggish, even moving then tachypnea, lusterless complexion or dark and gloomy, cough and spit is vexed, red tongue is dark or dark reddish purple, the trickle knot of deep pulse generation.Modern medicine is called coronary atherosclerotic heart disease (abbreviation coronary heart disease) or angina pectoris." Medical Treasures of the Golden Chamber obstruction of qi in the chest and cardialgia lose heart abnormal pulse card control " said: " pain over the chest and back is losed heart, pulse at CUN KOU being deep and slow for the disease of the thoracic obstruction, dyspnea and expectoration ... "." interior " cloud through numbness opinion the 43: " obstruction of heart-QI person, arteries and veins is obstructed, and tired then severe palpitation is gone up gas cruelly and is breathed heavily, dry sensation in the pharynx, frequent eructation is then feared on the gas of fainting "." be the arteries and veins blood clotting and do not flow ".
Coronary heart disease is because of coronary atherosclerosis, the heart change that myocardial blood supply development obstacle causes, and its pathogeny is complicated combined process, is divided into four-stage: the one, the cardiovascular endotheliocyte is impaired, vascular smooth muscle cell curing; The 2nd, platelet adhesion discharges serotonin, thromboxane A after impaired blood vessel wall
2, platelet IV, the VIII factor etc.; The 3rd, low density lipoprotein, LDL infiltrates subintimal smooth muscle cell by impaired endotheliocyte, and is engulfed, and enters to be decomposed by lysosomal hydrolytic enzyme in the cell behind the cell and discharge free gallbladder alcohol, and the latter and linoleic acid are combined into important morbidity link; The 4th, on the basis of above-mentioned pathology, coronary artery fibrosis, calcification finally take place, suffocated breathing gently then uncomfortable in chest is heavy then angina pectoris, myocardial infarction, arrhythmia even sudden death take place.In the complete dead rate of China resident, heart disease ranking the 3rd.
The so-called apoplexy of the traditional Chinese medical science is meant sudden faint, the facial hemiparalysis that continues, hemiplegia, even remain unconscious.Be the apoplexy of modern medicine indication, the present invention at be ischemia apoplexy, i.e. ischemia apoplexy and apoplexy sequela." miscellaneous diseases source and course rhinoceros candle " cloud: " life five threescores, QI and blood just declines, and is the disease that apoplexy is arranged, young and vigorous nothing is also "." key to Diagnosis and Treatment " said: " fertile people has apoplexy more, with its arrogant in outside and regret in also interior." " element asks arcane truth former sick formula " say: " people's fertilizer is the fine and close and how strongly fragrant rapids of space between skin and muscles then, and QI and blood then is difficult to pass through, so many apoplexys "." Principle and Prohibition for Medical profession " cloud: " hemiplegia meciless, all deficiency of YANG QI is hungry, due to can not charging ".
Apoplexy or apoplexy sequela are because angiemphraxis, and anoxia or malnutrition cause the ischemic necrosis of neuron, neural lipid and vascular system or softening, cerebrovascular ranking the second in the complete dead rate of China resident, and disability rate is more than 60%.
The phlegm retention pulmonary distension of theory of Chinese medical science indication card, card see cough, pant, in the heart distension, sputum be jammed, chest pain cardiopalmus, moving phase more so, a little less than the dim complexion, lip dark purple purplish tongue, deep-thready pulse, even knot for etc., i.e. the pulmonary hypertension of modern medicine indication.
Pulmonary hypertension is that the pulmonary artery pressure pressure that a series of lung breast disease and other diseases are caused is higher than normal value, pulmonary artery endothelial tissue pathological change, the right ventricle plumpness, the pulmonary circulation oxygen content is lower than the disease of normal value, pulmonary hypertension is comparatively common in China, as pulmonary heart disease and some virogenetic respiratory system infectious disease often with pulmonary hypertension.
The medicine that is used for cardiovascular and cerebrovascular disease at present is more, and controlling symptoms is based on chemical drugs, and Chinese medicine is in the majority with oral formulations, and the injection kind is few, and the oral preparation of Chinese traditional medicinal bioavailability is low, and effect is not ideal enough.In existing this class injection with the Herba Erigerontis medical material be raw material Herba Erigerontis injection and Breviscapini injection arranged.The Herba Erigerontis medical material contains flavonoid and caffeic acid ester two big effective constituents, Herba Erigerontis injection mainly contains the caffeic acid esters, scutellarin content is less, be equivalent to medical material 3g, contain caffeic acid ester 20～30mg, contain scutellarin and count 2～4mg, show that the extraction and separation process of existing Herba Erigerontis injection is unreasonable, the loss of scutellarin flavones ingredient is very big; And Breviscapini injection mainly contains the scutellarin flavones ingredient, does not contain the caffeic acid ester constituents, and every 10ml is equivalent to medical material 4g, contains scutellarin 20mg; High performance liquid chromatogram diode array detection (HPLC-DAD) figure of Herba Erigerontis injection and Breviscapini injection has remarkable difference.Therefore, with the former Herba Erigerontis injection that medical material feeds intake, scutellarin flavonoid loss is too high, has wasted resource, and the preparation technology of the Breviscapini injection that feeds intake with total flavones loses the loss of effective site caffeic acid esters to the greatest extent, and the wasting of resources is bigger.This extraction and purification process that proves absolutely existing Herba Erigerontis injection and Breviscapini injection is all unreasonable, be further improved, should keep contained scutellarin flavonoid and caffeic acid ester effective constituents in the Herba Erigerontis medical material as far as possible, through the research of extraction purification, thereby realized the present invention---erigeron breviscapus ketone ester and injection thereof.
Injection bioavailability height, the blood drug level height, the drug action performance is fast, quality controllable, meets modernization of Chinese medicine requirement.
Summary of the invention:
The objective of the invention is at treatment chest arthralgia precordial pain syndrome (angina pectoris), the problem that apoplexy (ischemia apoplexy and apoplexy sequela) medicine exists, for the world of medicine provides a kind of bioavailability height, the blood drug level height, drug action is fast, quality controllable, toxic and side effects and untoward reaction are little, make full use of the new drug of effective site in the medical material---the erigeron breviscapus ketone ester injection, comprising low capacity erigeron breviscapus ketone ester injection, high capacity erigeron breviscapus ketone ester sodium chloride injection, high capacity erigeron breviscapus ketone ester glucose injection, high capacity Herba Erigerontis glycerol injection, injection erigeron breviscapus ketone ester (lyophilized injectable powder).
Another object of the present invention provides the preparation method of this erigeron breviscapus ketone ester and injection thereof, this method has novelty, go out contained ketone ester two big effective kind parts from the Herba Erigerontis medicinal material extract, purity height (effective site content is up to more than 85%) not only, and utilized herb resource fully.
The objective of the invention is to realize by the medicine that following prescription and preparation technology produce.
A kind of erigeron breviscapus ketone ester injection composition by an amount of erigeron breviscapus ketone ester, adds appropriate amount of auxiliary materials and water for injection and forms.It is characterized in that used erigeron breviscapus ketone ester is the effective site of Herba Erigerontis, contains total flavonoid and total coffee acid ester.
Additional technical feature:
A. low capacity erigeron breviscapus ketone ester injection, by erigeron breviscapus ketone ester 100～200mg, water for injection adds to 5～10ml and forms.
B. high capacity erigeron breviscapus ketone ester sodium chloride injection, by erigeron breviscapus ketone ester 100～200mg, injection total amount 0.9% sodium chloride, water for injection add to 50～100ml and form.
C. high capacity erigeron breviscapus ketone ester glucose injection, by erigeron breviscapus ketone ester 100～200mg, injection total amount 5% glucose, water for injection add to 50～100ml and form.
D. high capacity erigeron breviscapus ketone ester glycerol injection, by erigeron breviscapus ketone ester 100～200mg, injection total amount 2.6% (W/V) glycerol, water for injection add to 50～100ml and form.
E. injection erigeron breviscapus ketone ester (lyophilized injectable powder), by erigeron breviscapus ketone ester 65～130mg, make bulking agent with the mannitol of 150～200mg or glucosan or xylitol or sorbitol, add the injection water and add to 2.5～3ml and form, make 0.25～0.40g lyophilized injectable powder through lyophilization.
Erigeron breviscapus ketone ester of the present invention and injection thereof are made up of erigeron breviscapus ketone ester extraction and purification process and process for preparation of injection.Wherein the extraction and purification process of erigeron breviscapus ketone ester is: get the Herba Erigerontis coarse powder, with 8 times of amount 75% alcohol reflux 3 times, each 1 hour, merge pure liquid, filter, filtrate is concentrated into every 1ml and is equivalent to about medical material 1g at 95 ℃ of following decompression recycling ethanol, and cold preservation is spent the night, filter, sodium hydroxide with 10% is regulated about pH to 8.0, and heating for dissolving adds 0.5% (W/V) active carbon and stirs evenly, about 10 minutes of insulation absorption, filtered while hot, filtrate under agitation slowly add 20% sulfuric acid solution, regulate pH to 2～3, cold preservation is spent the night, centrifugal after-filtration, precipitation is washed with water to neutrality, precipitates standby; Filtrate has been concentrated into precipitation and has produced (separating out), is cooled to 50 ℃, the leaching precipitation, and reconcentration is to there being precipitation to separate out, with method collecting precipitation, filtrate for later use; Merge precipitation 3 times, wash with water 2～3 times, 75% ethanol is washed 2～3 times, and pure washing liquid is standby; The pure water that precipitation adds 1/5 medical material amount stirs evenly, and adds 10% sodium hydroxide solution and regulates pH value about 8.0, adds 0.5% (W/V) active carbon after the heating for dissolving and stirs evenly, about 10 minutes of insulation absorption, filter while hot, filtrate under agitation slowly adds 20% sulfuric acid solution and regulates pH value 2～3, leaves standstill about 2 hours, filter, with pure water washing 2～3 times, reuse 75% washing with alcohol 2～3 times, collecting precipitation, promptly get Herba Erigerontis total flavones, standby; Collect last sedimentary filtrate, be concentrated into every 1ml and be equivalent to about medical material 10g, last polyamide column (post footpath is 1:5～6 with the post height ratio, the polyamide consumption be the medical material amount 15%), be washed with water to water liquid pH value to 5～6 earlier, water lotion is standby; Reuse 75% ethanol is washed till light yellow, at 95 ℃ of following decompression recycling ethanols, and is concentrated into every 1ml and is equivalent to promptly get the Herba Erigerontis caffeic acid esters about medical material 10g, and is standby; Get above-mentioned standby pure washing liquid, being concentrated into every 1ml with above-mentioned water lotion heating behind the recovery ethanol is equivalent to about medical material 10g, about cold preservation 4 hours, filter, (the post footpath is 1:5～6 with the post height ratio to polyamide column on the filtrate, consumption be the medical material amount 10%), be washed with water to pH value 5～6 earlier, reuse 75% ethanol is washed till faint yellow, at 95 ℃ of following reclaim under reduced pressure sec-butyl alcohols, and is concentrated into every 1ml and is equivalent to about medical material 20g, merge with above-mentioned total coffee acid ester concentrated solution, and add above-mentioned Herba Erigerontis total flavones, and add about 10% sodium hydroxide solution adjusting pH value to 7.5, heating is concentrated into the thick paste shape, vacuum drying under about 85 ℃, promptly get erigeron breviscapus ketone ester (intermediate), sealing is preserved, and is standby.
The injection preparation is characterised in that: get erigeron breviscapus ketone ester 100～200mg, the water for injection that adds recipe quantity about 20%, regulate about pH value to 7.0, be heated to and boil, add the about 10min of adsorbents adsorb, filtering decarbonization removes adsorbent, add to the full amount of water for injection, the high capacity sodium chloride injection adds injection total amount 0.9% sodium chloride, the high capacity glucose injection adds injection total amount 5% glucose, high capacity glycerol injection adds injection total amount 2.6% (W/V) glycerol, lyophilized injectable powder adds 150～200mg mannitol or glucosan or sorbitol or xylitol, regulates pH value, fine straining is clear and bright, embedding, sterilization, lamp inspection, packing, product inspection; Lyophilized injectable powder is through lyophilization, and product inspection is packed promptly.
The invention has the advantages that: the bioavailability height, the blood drug level height, the drug effect performance is fast, and quality controllable, toxic and side effects and untoward reaction are little, have made full use of the effective site of Herba Erigerontis, have avoided the wasting of resources.The injection of making by erigeron breviscapus ketone ester (containing flavonoid, caffeic acid ester), the test of pesticide effectiveness proves, treatment chest arthralgia precordial pain syndrome (angina pectoris) and apoplexy (ischemic brain infarction and cerebral infarction sequela), determined curative effect, more former fleabane injection of drug effect and former Herba Erigerontis injection all strengthen.
Drug therapy cardiovascular and cerebrovascular vessel theoretical foundation of the present invention is as follows:
Theory of Chinese medical science is thought: the main pathogenesis of chest arthralgia precordial pain syndrome is a phlegm and blood stasis, upright excessive outer attacking, feelings will does not save etc., is directed at blockage of the vessel, stagnates and forms the stasis of blood, blood stasis then closes, close to form numbness, numbness then the five internal organs lose support, imbalance, decline to the positive deficiency of vital energy eventually.The primary disease excess syndrome is cold coagulation, the stagnation of QI, blood stasis, numbness resistance chest pain, stagnating heart meridian, is numbness at the heart, is apoplexy at brain, so the useful heart leads to brain, blood circulation promoting and blood stasis dispelling, the network that relaxes is promoted blood circulation to separate the reality of the stasis of blood.Herba Erigerontis is a suffering, little hardship, and Xin Shantong lives, and is warm in nature, and Wen Nenghang looses, the logical energy blood stasis dispelling of living, row looses and can reduce phlegm, and the heart, brain, venation are with living, and the promoting the circulation of blood inducing QI causes merit cold, promoting blood circulation, dredging meridian and relieving pain so have to dispel the wind, and meets theory of Chinese medical science.
Modern pharmacy studies show that: Herba Erigerontis effective site is flavonoid and caffeic acid esters, i.e. erigeron breviscapus ketone ester.Erigeron breviscapus ketone ester can reduce the heart, cerebral vascular resistance, increases the heart, cerebral blood flow, microcirculation improvement, improve cerebral ischemia reperfusion cerebral tissue blood flow, suppress PKC excessive activation or displacement and activate, suppress outer accumulation of EAA extracellular domain amino acid and intracellular calcium overload, prevent that oxygen-derived free radicals from generating, while is blood viscosity lowering significantly, anticoagulant reduces the plump index of right ventricle, improves due to the myocardial ischemia ST section and raises, reduce anoxia myocardial cell LDH, AST, CK, antagonism thrombosis.
Contained flavonoid of erigeron breviscapus ketone ester and caffeic acid esters are erigeron breviscapus effective component, the ketone ester class is share, not only make the ischemia apoplexy and the apoplexy sequela of treatment chest arthralgia precordial pain syndrome (angina pectoris), apoplexy more effective, also improved the medical material utilization rate simultaneously.
Pharmacological toxicology studies show that: erigeron breviscapus ketone ester injection energy anticoagulant of the present invention, prolong prothrombin time, strengthen plasmin activity (P＜0.01), reduce fibrin matter, promote antigen in conjunction with born of the same parents' hypertrophy, improve body macrophage phagocytic immunologic function; Reduce hypertrophy of right heart index (P＜0.05), remarkable coronary artery dilator, coronary blood flow increasing reduces myocardial oxygen consumption, improves myocardial ischemia (P＜0.01), suppresses LPC and produces, and increases SOD, GSH-Px, CTA, the Na of cerebral tissue
+, K
+-ATP activity, cerebral blood flow increasing amount, microcirculation improvement; increase medium-sized artery mean flow rate and peak velocity (P＜0.01), significantly reduce LDH to brain tissue damage, the brain tissue impairment that cerebral ischemia re-pouring is caused has converse protective effect; reduce infarction size, suppress heart rate from the pleth (P＜0.01).
Acute toxicity test shows: give after mice or the rat injection by 850 times and 721 times of 60kg body weight adult vein consumption per day, observed 14 days, animal does not have death, food ration and body weight do not have obvious minimizing, observe vitals (heart, liver, spleen, lung, kidney etc.) after putting to death animal, all no abnormal discovery, all the other are no abnormality seen also.
Long term toxicity test shows, continuously to the intravenous drip of Beagle dog, presses 60kg body weight adult's 50 times of medicines of intravenously administrable consumption per day and drug withdrawal and observes in 30 days, shows no obvious abnormalities, and does not also have obvious retardance toxic reaction.
Clinical experimental study shows: the erigeron breviscapus ketone ester injection has the function of the logical brain of the beneficial heart, blood circulation promoting and blood stasis dispelling, analgesic, being mainly used in the positive deficiency of vital energy of treatment declines, chest arthralgia precordial pain syndrome due to the blockage of the vessel (angina pectoris) and apoplexy (ischemia apoplexy and apoplexy sequela), low capacity erigeron breviscapus ketone ester injection, once a day, each 1～2 dosage unit or follow the doctor's advice adds 5% glucose injection or 0.9% sodium chloride injection, 50～100ml, venoclysis; High capacity erigeron breviscapus ketone ester sodium chloride (glucose or glycerol) injection, once a day, each 1～2 dosage unit or follow the doctor's advice venoclysis; Injection erigeron breviscapus ketone ester (lyophilized injectable powder), once a day, each 1～2 dosage unit or follow the doctor's advice adds 5% glucose or sodium chloride injection 50～100ml venoclysis.The erigeron breviscapus ketone ester injection is 75.3% to the obvious effective rate of chest arthralgia precordial pain syndrome (angina pectoris), and effective percentage is 21.7%, total effective rate 97.0%; To the cerebral infarction of apoplexy and the obvious effective rate of cerebral infarction sequela is 74.1%, and effective percentage is 22.5%, total effective rate 96.6%.
Description of drawings:
Fig. 1 is preparation technology's flow chart of erigeron breviscapus ketone ester of the present invention
Fig. 2 is a low capacity erigeron breviscapus ketone ester injection preparation technology flow chart of the present invention
Fig. 3 is a high capacity erigeron breviscapus ketone ester chloride injection liquid preparing process flow chart of the present invention
Fig. 4 is a high capacity erigeron breviscapus ketone ester glucose injection liquid preparing process flow chart of the present invention
Fig. 5 is a high capacity erigeron breviscapus ketone ester glycerol injection preparation technology flow chart of the present invention
Fig. 6 is injection erigeron breviscapus ketone ester of the present invention (lyophilized injectable powder) preparation technology flow chart
The specific embodiment
Preparation technology:
Erigeron breviscapus ketone ester prepares as follows: get the Herba Erigerontis medicinal material coarse powder, measure 75% alcohol reflux 3 times with 8 times, each 1h merges pure liquid, filtrate, filtrate is at 95 ℃ of following decompression recycling ethanols, be concentrated into every 1ml and be equivalent to about medical material 1.5g, cold preservation is spent the night, with filtered through gauze (removing the block impurity of black), sodium hydroxide with 10% is regulated about pH value to 8.0, be heated to and boil, add 1% (W/V) activated carbon adsorption, about 10 minutes of insulation absorption, filtered while hot, filtrate under agitation slowly adds 20% sulfuric acid solution, regulates pH value to 2～3, and cold preservation is spent the night, centrifugal, precipitate standby; Supernatant concentration is cooled to about 50 ℃ to there being precipitation to separate out, the leaching precipitation, and reconcentration is to there being precipitation to separate out, with method collecting precipitation, filtrate for later use; Merge precipitation 3 times, 75% ethanol is washed 2～3 times, wash with water 2～3 times, reuse washing with alcohol 1～2 time, the pure water that adds 1/5 medical material amount stirs evenly, and adds 10% sodium hydroxide solution and regulates pH value about 8.0, adds 0.5% (W/V) active carbon after the heating for dissolving and stirs evenly, about 10 minutes of insulation absorption, filter while hot, filtrate under agitation slowly adds 20% sulfuric acid solution and regulates pH value 2～3, leaves standstill about 2 hours, filter, with 75% washing with alcohol 2～3 times, reuse pure water washing 2～3 times, collecting precipitation, promptly get Herba Erigerontis total flavones, standby; Collect last sedimentary filtrate, be concentrated into every 1ml and be equivalent to about medical material 10g, last polyamide column (post footpath is 1:5～6 with the post height ratio, the polyamide consumption be medicine just measure 15%, i.e. 450g), be washed with water to pH value of water solution to 5～6 earlier, wash standby; Reuse 75% ethanol elution to eluent is little yellow, at 95 ℃ of following decompression recycling ethanols, and is concentrated into every 1ml and is equivalent to promptly get Herba Erigerontis caffeic acid esters's concentrated solution about medical material 10g, and is standby; The heating of water intaking washing liquid is concentrated into every 1ml and is equivalent to about medical material 10g, about cold preservation 4 hours, filter, (the post footpath is 1:5～6 with the post height ratio to polyamide column on the filtrate, consumption be the medical material amount 10%), earlier be washed till pH value 5～6 with pure water, reuse 75% ethanol is washed till faint yellow, at 95 ℃ of following decompression recycling ethanols, being concentrated into every 1ml is equivalent to about medical material 20g, merge with above-mentioned caffeic acid ester concentrated solution, add above-mentioned Herba Erigerontis total flavones, and add about 10% sodium hydroxide solution adjusting pH value to 7.5, heating is concentrated into the thick paste shape, at 85 ℃ of following vacuum dryings, promptly get Herba Erigerontis extract (intermediate), cold preservation is standby.
Low capacity erigeron breviscapus ketone ester injection is prepared finished product as follows:
Get erigeron breviscapus ketone ester 65～130mg, the water for injection that adds recipe quantity about 20%, add the about 10min of 0.3% (W/V) activated carbon adsorption, filtering decarbonization adds to the full amount of water for injection, regulate about pH to 7.0 with 10% sodium hydroxide solution, be heated to and boil, clear and bright with 0.45 μ m and 0.22 μ m filter membrane fine straining, embedding is in the bent neck ampoule of 5～10ml, 100 ℃ of sterilization 30min, through leak detection, lamp inspection, lettering, product inspection, packing promptly.
Embodiment A low capacity erigeron breviscapus ketone ester injection
Example 1 is by erigeron breviscapus ketone ester 100mg, and water for injection adds to 5ml and forms.
Example 2 is by erigeron breviscapus ketone ester 200mg, and water for injection adds to 10ml and forms.
High capacity erigeron breviscapus ketone ester sodium chloride injection is prepared finished product as follows:
Get erigeron breviscapus ketone ester 100～200mg, the sodium chloride that adds injection total amount 0.9% (W/V) adds the water for injection of recipe quantity about 20%, regulates about pH value to 7.0, heated and boiled, add the about 10min of 0.3% (W/V) activated carbon adsorption, filtering decarbonization adds to the full amount of water for injection, regulate about pH to 7.0, fine straining is clear and bright, and embedding is in 50～100ml infusion bottle, and sterilization, lamp inspection, decals, product inspection, packing are promptly.
Embodiment B high capacity erigeron breviscapus ketone ester sodium chloride injection
Example 1 is by erigeron breviscapus ketone ester 100mg, and sodium chloride 0.45g, water for injection add to 50ml and form.
Example 2 is by erigeron breviscapus ketone ester 200mg, and sodium chloride 0.9g, water for injection add to 100ml and form.
High capacity erigeron breviscapus ketone ester glucose injection is prepared finished product as follows:
Get erigeron breviscapus ketone ester 100～200mg, add the glucose of injection total amount 5% (W/V), add the water for injection of recipe quantity about 20%, regulate about pH value to 6.0, heated and boiled adds the about 10min of 0.3% (W/V) activated carbon adsorption, filtering decarbonization, add to the full amount of water for injection, regulate about pH to 6.0, fine straining is clear and bright, after the inspection of semifinished product is qualified, embedding is in 50～100ml infusion bottle, and sterilization, lamp inspection, decals, product inspection, packing are promptly.
Embodiment C high capacity erigeron breviscapus ketone ester glucose injection
Example 1 is by erigeron breviscapus ketone ester 100mg, and glucose 2.5g, water for injection add to 50ml and form.
Example 2 is by erigeron breviscapus ketone ester 200mg, and glucose 5g, water for injection add to 100ml and form.
High capacity erigeron breviscapus ketone ester glycerol injection is prepared finished product as follows:
Get erigeron breviscapus ketone ester 100～200mg, the glycerol that adds injection total amount 2.6% (W/V) adds the water for injection of recipe quantity about 20%, regulates about pH value to 7.0, heated and boiled, add the about 10min of 0.3% (W/V) activated carbon adsorption, filtering decarbonization adds to the full amount of water for injection, fine straining is clear and bright, after the inspection of semifinished product was qualified, embedding was in 50～100ml infusion bottle, and sterilization, lamp inspection, decals, product inspection, packing are promptly.
Embodiment D high capacity erigeron breviscapus ketone ester glycerol injection
Example 1 is by erigeron breviscapus ketone ester 100mg, and glycerol 1.3g, water for injection add to 50ml and form.
Example 2 is by erigeron breviscapus ketone ester 200mg, and glycerol 2.6g, water for injection add to 100ml and form.
Injection erigeron breviscapus ketone ester (lyophilized injectable powder) is prepared finished product as follows:
Get erigeron breviscapus ketone ester 100～200mg, mannitol or sorbitol or xylitol or Dextran 150～200mg, the water for injection that adds recipe quantity about 60%, heated and boiled, add the about 10min of adsorbents adsorb, the filtering and removing adsorbent, water for injection adds to 2.5～3ml, composite microporous filter filtration sterilization with 0.45 μ m and 0.22 μ m microporous filter membrane composition, pack in sterilized 7～10ml lyophilizing bottle pre-freeze, lyophilization then under the aseptic condition into, make 0.25～0.4g lyophilized injectable powder, seal, decals, product inspection, packing promptly.
Embodiment E injection erigeron breviscapus ketone ester (lyophilized injectable powder)
By erigeron breviscapus ketone ester 100～200mg, mannitol or sorbitol or xylitol or glucosan 180mg, water for injection add to 2.5～3.0ml and form.
Example 1 is by erigeron breviscapus ketone ester 100mg, and mannitol 150mg, water for injection add to 2.5ml and form, and make lyophilized injectable powder 0.25g/ bottle.
Example 2 is by erigeron breviscapus ketone ester 100mg, and xylitol 150mg, water for injection add to 2.5ml and form, and make lyophilized injectable powder 0.25g/ bottle.
Example 3 is by erigeron breviscapus ketone ester 100mg, and glucose 150mg, water for injection add to 2.5ml and form, and make lyophilized injectable powder 0.25g/ bottle.
Example 4 is by erigeron breviscapus ketone ester 100mg, and Dextran 150 mg, water for injection add to 2.5ml and form, and make lyophilized injectable powder 0.25g/ bottle.
Example 5 is by erigeron breviscapus ketone ester 200mg, and mannitol 200mg, water for injection add to 3ml and form, and make lyophilized injectable powder 0.4g/ bottle.
Example 6 is by erigeron breviscapus ketone ester 200mg, and sorbitol 200mg, water for injection add to 3ml and form, and make lyophilized injectable powder 0.4g/ bottle.
Example 7 is by erigeron breviscapus ketone ester 200mg, and glucose 200mg, water for injection add to 3ml and form, and make lyophilized injectable powder 0.4g/ bottle.
Example 8 is by erigeron breviscapus ketone ester 200mg, and Dextran 200 mg, water for injection add to 3ml and form, and make lyophilized injectable powder 0.4g/ bottle.
Example 9 is by erigeron breviscapus ketone ester 200mg, and xylitol 200mg, water for injection add to 3ml and form, and make lyophilized injectable powder 0.4g/ bottle.
Claims (9)
1. a beneficial heart leads to brain, blood circulation promoting and blood stasis dispelling, the Herba Erigerontis extract erigeron breviscapus ketone ester of analgesic, the total content of flavonoid and caffeic acid esters is not less than 85% in the erigeron breviscapus ketone ester, it is characterized in that in the active component of this extract, the content of flavonoid is 50%, the content of caffeic acid ester is 40%, this preparation method of extract is, get the Herba Erigerontis coarse powder, measure 75% alcohol reflux 3 times for 8 times, each 1h, extracting solution is concentrated into 1ml and is equivalent to medical material 1g approximately, cold preservation is spent the night, filter, transfer about pH to 8.0 with 10% NaOH liquid, 0.5% active carbon insulation absorption is used 20% H with filtrate after about 10 minutes
2SO
4Transfer pH to 2～3, cold preservation is spent the night, centrifugal collecting precipitation; Concentrated supernatant and leaching precipitation repeat this settling step once, filtrate for later use.Merge precipitation 3 times, water, 75% ethanol are washed respectively 2～3 times, and pure washing liquid is standby, precipitation stirs evenly with pure water, adopts with said extracted liquid and leaves standstill about 2h, filtration after with the method adjust pH, precipitation is washed respectively 2～3 times with pure water, 75% ethanol, gets Herba Erigerontis total flavones.Standby filtrate is concentrated into every 1ml is equivalent to medical material 10g approximately, polyamide column, the post footpath: the post height is 1:5～6, the polyamide consumption is a medical material amount 15%, wash with water to water liquid pH value 5～6, reuse 75% ethanol is washed till light yellow, and pure washing liquid is concentrated into every 1ml and is equivalent to medical material 10g approximately, gets Herba Erigerontis caffeic acid esters's concentrated solution; Water lotion and standby pure washing liquid are concentrated into every 1ml to be equivalent to about medical material 10g, the about 4h after-filtration of cold preservation, polyamide column on the filtrate, the post footpath: the post height is 1:5～6, and the polyamide consumption is a medical material amount 15%, with the method eluting, the alcohol washing liquid is concentrated into every 1ml and is equivalent to medical material 20g approximately, adds above-mentioned total coffee acid ester concentrated solution and Herba Erigerontis total flavones, about adjust pH to 7.5, concentrate drying promptly gets erigeron breviscapus ketone ester.
2. the described erigeron breviscapus ketone ester of claim 1 adds the injection that medicinal adjuvant and water for injection are made, and comprises low capacity erigeron breviscapus ketone ester injection, high capacity erigeron breviscapus ketone ester sodium chloride injection, high capacity erigeron breviscapus ketone ester glucose injection, high capacity Herba Erigerontis glycerol injection, erigeron breviscapus ketone ester lyophilized injectable powder.
3. the described low capacity erigeron breviscapus ketone ester of claim 2 injection is characterized in that erigeron breviscapus ketone ester 100mg, wherein contains flavonoid and is not less than 48mg, and the caffeic acid esters is not less than 37mg, adds injection water to 5～10ml.
4. the described high capacity erigeron breviscapus ketone ester of claim 2 sodium chloride injection, it is characterized in that erigeron breviscapus ketone ester 100mg, wherein contain flavonoid and be not less than 48mg that the caffeic acid esters is not less than 37mg, the sodium chloride of injection total amount 0.9% adds injection water to 50～100ml.
5. the described high capacity erigeron breviscapus ketone ester of claim 2 glucose injection, it is characterized in that erigeron breviscapus ketone ester 100mg, wherein contain flavonoid and be not less than 48mg that the caffeic acid esters is not less than 37mg, the glucose of injection total amount 5% adds injection water to 50～100ml.
6. the described high capacity erigeron breviscapus ketone ester of claim 2 glycerol injection, it is characterized in that erigeron breviscapus ketone ester 100mg, wherein contain flavonoid and be not less than 48mg that the caffeic acid esters is not less than 37mg, the glycerol total amount is 2.6%W/V, adds injection water to 50～100ml.
7. the described erigeron breviscapus ketone ester lyophilized injectable powder of claim 2, it is characterized in that erigeron breviscapus ketone ester 100mg, wherein contain flavonoid and be not less than 48mg, the caffeic acid esters is not less than 37mg, mannitol or xylitol or sorbitol or Dextran 150 mg, add injection water to 2.5～3ml, make the 0.25g lyophilized injectable powder through lyophilization.
8. the described injection of claim 2, the pharmaceutic adjuvant that adds when making injection are meant a kind of in sodium chloride, glucose, glycerol, mannitol, sorbitol or the glucosan.
9. the preparation method of the described Herba Erigerontis effective site of claim 1 erigeron breviscapus ketone ester, it is characterized in that: get the Herba Erigerontis coarse powder, measure 75% alcohol reflux 3 times for 8 times, each 1h, extracting solution is concentrated into 1ml and is equivalent to medical material 1g approximately, the cold preservation filtration of spending the night is transferred about pH to 8.0 with 10% NaOH liquid, and 0.5% active carbon insulation absorption is used 20% H with filtrate after about 10 minutes
2SO
4Transfer pH to 2～3, cold preservation is spent the night, centrifugal collecting precipitation; Concentrated supernatant and leaching precipitation repeat this settling step once, filtrate for later use.Merge precipitation 3 times, water, 75% ethanol are washed respectively 2～3 times, and pure washing liquid is standby, precipitation stirs evenly with pure water, adopts with said extracted liquid and leaves standstill about 2h, filtration after with the method adjust pH, precipitation is washed respectively 2～3 times with pure water, 75% ethanol, gets Herba Erigerontis total flavones.Standby filtrate is concentrated into every 1ml is equivalent to medical material 10g approximately, last polyamide column, the post footpath: the post height is 1:5～6, the polyamide consumption is a medical material amount 15%, wash with water to water liquid pH value 5～6, reuse 75% ethanol is washed till light yellow, and pure washing liquid is concentrated into every 1ml and is equivalent to medical material 10g approximately, gets Herba Erigerontis caffeic acid esters's concentrated solution; Water lotion and standby pure washing liquid are concentrated into every 1ml to be equivalent to about medical material 10g, the about 4h after-filtration of cold preservation, polyamide column on the filtrate, the post footpath: the post height is 1:5～6, and the polyamide consumption is a medical material amount 15%, with the method eluting, the alcohol washing liquid is concentrated into every 1ml and is equivalent to medical material 20g approximately, adds above-mentioned total coffee acid ester concentrated solution and Herba Erigerontis total flavones, about adjust pH to 7.5, concentrate drying promptly gets erigeron breviscapus ketone ester.
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| CN100462082C true CN100462082C (en) | 2009-02-18 |
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| CN104586911B (en) * | 2014-04-21 | 2016-01-27 | 林艳和 | Pharmaceutical composition containing caffeic acid ester and lamp-dish flower acetic and its preparation method and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1462620A (en) * | 2003-04-22 | 2003-12-24 | 中国科学院昆明植物研究所 | Powder of flenabane and its preparation method as well as application in making drugs |
| CN1476842A (en) * | 2003-07-15 | 2004-02-25 | 中国人民解放军第二军医大学 | Fleabane extract and dicaffeoylquinic acid medicine composition and its application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1462620A (en) * | 2003-04-22 | 2003-12-24 | 中国科学院昆明植物研究所 | Powder of flenabane and its preparation method as well as application in making drugs |
| CN1476842A (en) * | 2003-07-15 | 2004-02-25 | 中国人民解放军第二军医大学 | Fleabane extract and dicaffeoylquinic acid medicine composition and its application |
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