CN101757068A - Breviscapine frozen dry powder for injection and preparation method thereof - Google Patents
Breviscapine frozen dry powder for injection and preparation method thereof Download PDFInfo
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- CN101757068A CN101757068A CN200810153363A CN200810153363A CN101757068A CN 101757068 A CN101757068 A CN 101757068A CN 200810153363 A CN200810153363 A CN 200810153363A CN 200810153363 A CN200810153363 A CN 200810153363A CN 101757068 A CN101757068 A CN 101757068A
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Abstract
The invention provides a Breviscapine frozen dry powder for injection and a preparation method thereof. The Breviscapine frozen dry powder is prepared by adding a certain proportion of medicinal excipient to a Breviscapine extractive. The Breviscapine frozen dry powder has the characteristics of good dissolubility and stable property, thereby being especially suitable for treating blood stasis coronary disease, angina, arrhythmia, blood stasis pain and the like.
Description
Technical field
The present invention relates to prevention and treatment treating coronary heart disease and angina pectoris and preparation method thereof.Specifically, be a kind of freeze-dried powder that contains breviscapine extract and pharmaceutical excipient and preparation method thereof.
Background technology
Angina pectoris often shows as squeezing pain, constriction, sensation of asphyxia, burning pain, the weight of the breastbone middle and upper part of unexpected generation and presses the breast sense, and chest pain increases the weight of gradually, reaches climax in several minutes, and can be radiated to shoulder inboard, a left side, cervical region, lower jaw, last midriff or both shoulders.With cold sweat, alleviate gradually later on, the persistent period is a few minutes, can alleviate through having a rest or obeying nitroglycerin.The person of not being true to type can be at inferior segment sternotomy, tenderness before the epigastrium or the heart.The pain that the radiation position is only arranged that has, stuffy as throat, lower jaw is painful, the cervical vertebra tenderness.Old people's symptom often is not true to type, and can only feel uncomfortable in chest, breathes hard, tired.Sensile diabetic patient even only feel uncomfortable in chest and do not have chest pain performance.The fatigue angina pectoris: the anginal feature of fatigue is the of short duration chest pain outbreak of being brought out by motion or other situation that increases myocardium requirementing keto quantity, and behind rest or the sublingual administration nitroglycerin, pain often can rapidly disappear.Spontaneous angina pectoris: the feature of spontaneous angina pectoris is that the chest pain outbreak does not have obvious relation with the increase of myocardium requirementing keto quantity.Compare with the fatigue angina pectoris, this pain general persistence is longer, and degree is heavier, and is difficult for alleviating for nitroglycerin, does not see enzymic change.Electrocardiogram some temporary S-T section often occurs and forces down the change of T ripple.Spontaneous angina pectoris can take place separately or merge existence with the fatigue angina pectoris.The spontaneous angina pectoris patient can have different clinical manifestations because of pain seizure frequency, persistent period and pain degree.Sometimes, the patient can have long-term chest pain outbreak, similar myocardial infarction, but do not have the characteristic of electrocardiogram and enzyme to change.Temporary ST section occurs during some spontaneous angina pectoris patient's outbreak and raise, often be called variant angina pectoris.But when myocardial infarction records this ECG pattern in early days, just send out fatigue angina pectoris, progressive angina pectoris and spontaneous angina pectoris and often be called " unstable angina pectoris ".The classical angina symptom comprises five aspects: (one) painful area.Most of angina pectoris is positioned at the shirtfront, can take back, and also can be throat portion pain.Scope can be little as a fist, but also great achievement a slice spreads all over full breast.(2) pain character.Angina pectoris is a kind of dull pain, and companion's constriction is felt oppressed, discomforts such as obstruction, deflation, heating.Degree can gently can weigh, and the severe outbreak can be accompanied profuse sweating, dying sense.(3) persistent period.Angina pectoris attacks, is alleviated to heavy afterwards gradually by gently, only continues 3～5 minutes.Surpass 15 minutes as outbreak, just should seek medical advice at once, in order to avoid develop into myocardial infarction.(4) risk factor.Physical exertion mostly is common inducement.Perhaps in the presence of factors such as cold, heavy meal, excessive drinking and smoking, angina pectoris is easier to be brought out by fatigue.In addition, bad Nervous and Mental Factors stimulation also can be brought out angina pectoris attacks.(5) alleviation mode.Behind the angina pectoris attacks, remove risk factor, as stop action, symptom is alleviated automatically.The patient gets seat or reliable upright position more helps remission than clinostatism.Sublingual administration nitroglycerin 1～2 (3 milligrams～6 milligrams) can make remission in 1～3 minute, duration of seizure is obviously shortened.The indication of Herba Erigerontis tablet, indication blood circulation promoting and blood stasis dispelling, removing obstruction in the collateral to relieve pain.Be used for apoplexy sequela, coronary heart disease, angina pectoris.System extracts the refining oral tablets that form such as flavonoids effective constituent breviscapine from the Herba Erigerontis Herb plant of the Yunnan-Guizhou Plateau.Mainly contain anticoagulation, antithrombotic formation, improve hemorheological property and microcirculation, the cerebral blood flow increasing amount resists myocardial ischemia, and improves effects such as body's hypoxia tolerance.Has blood circulation promoting and blood stasis dispelling, removing obstruction in the collateral to relieve pain.Be used for the treatment of cardiovascular and cerebrovascular disease.As obliterative vascular disease, cerebral thrombosis, vasculitis coronary heart disease, angina pectoris, to the acute stage of ischemic cerebrovascular, convalescent period and back are lost seized with terror. and as cerebral blood supply insufficiency, brain blood is fullyed recover from an illness, and waits the paralysis that causes, dementia and apoplexy etc.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, the freeze-dried powder of a kind of steady quality, treatment angina pectoris that active constituent content is high is provided.
The technical solution adopted in the present invention is: chest-relaxing freeze dried powder, it is made up of breviscapine water solubility extract and pharmaceutical excipient.The raw material of its parts by weight is composed as follows:
Breviscapine water solubility extract 10-100 part
Pharmaceutical excipient 2-30 part
Described breviscapine water solubility extract is the ethanol extraction that adopts water or arbitrary proportion, makes through column chromatographic isolation and purification, specifically comprises the following steps:
(1). the method that the breviscapine water solubility extract extracts respectively: get the breviscapine pulverizing medicinal materials and become coarse grain, adopt the ethanol extraction of water or arbitrary proportion, extracting method comprises decoction repeatedly, hot reflux, percolation, ultrasonic, microwave; Extracting solution concentrates or without concentrating through decompression (60～70 ℃); Extracting solution eliminates ethanol after macroporous resin column, water elution impurity, arbitrary proportion ethanol elution effective ingredient; Collect eluent, eliminate ethanol, get the breviscapine extracting solution; Or
(2) method of breviscapine water solubility extract mixed extraction: get the breviscapine pulverizing medicinal materials and become coarse grain; Mix the ethanol extraction of back water or arbitrary proportion, extracting method comprises decoction repeatedly, hot reflux, percolation, ultrasonic, microwave; Extracting solution concentrates or without concentrating through decompression (60～70 ℃); Extracting solution eliminates ethanol after macroporous resin column, water elution impurity, arbitrary proportion ethanol elution effective ingredient; Collect eluent, eliminate ethanol, get the breviscapine mixed extract.
Wherein, macroporous adsorbent resin can be HPD-100, D101, AB-8 or LSA-30; The eluent concentration of macroporous adsorbent resin is the ethanol of 30%-95%.
Described pharmaceutical excipient is mannitol, glucose, lactose or sorbitol.
The preparation of lyophilized powder injection of breviscapinum comprises following method:
(1) breviscapine extracting solution or mixed extract add excipient, stirring and dissolving;
(2) medicinal liquid adds the injection water to certain volume, and by the ultrafilter membrane degerming, under aseptic condition, packing;
(3) according to pre-conditioned lyophilization, gland, packing.
The present invention is in preparation freeze-dried powder process, and medicinal liquid divides the multistage lyophilizing.In freeze-drying process, medicinal liquid keeps 2～10h down freeze-drying curve temperature descending section temperature low spot-30～-70 ℃, keeps 1～10h down for 0～50 ℃ at the high point of temperature rise period temperature.Adopt noble gas to fill when encapsulation, guarantee to be difficult for oxidation takes place storage period, the storage time is long.
Freeze-dried powder of the present invention is compared advantage with prior dosage form and is:
This powder pin effective ingredient is clear and definite, and being convenient to the quality control breviscapine is main effective ingredient, and one-tenth is distinguished one from the other, the content height, and quality control is accurate, has improved product quality.The ultrafiltration degerming adopts freeze-drying to be made into pressed powder in the sterile working, can avoid medicine rotten because of hyperpyrexia decomposes.Overcome stimulation and the first pass effect of oral formulations to stomach.The injectable powder good stability owing to remove moisture, can prevent oxidation, hydrolysis, the inactivation of effective ingredient in water effectively, can guarantee content and curative effect better.
Below by pharmacodynamic experiment beneficial effect of the present invention is described:
Breviscapine frozen dry powder pharmacodynamic experiment of the present invention is the method that adopts ligation rat coronary artery anterior descending branch, cause the animal model of acute experiment myocardial ischemia, and observe breviscapine frozen dry powder to the animal pattern electrocardiogram, the influence of myocardial ischemia scope, serum biochemistry index.Result of the test shows: can obviously reduce the electrocardiogram S-T section that causes after the rat ligation branch of coronary artery and raise, administration group S-T section is raised and significantly is lower than the blank group.
Can improve experimental acute myocardial ischemia degree due to the ligation rat coronary artery anterior descending branch, dwindle myocardial infarct size, the infarct size of administration group accounts for the left ventricle area and is significantly less than the blank group.Have and reduce the active effect that raises of serum lactate dehydrogenase (SLD), administration group serum lactate dehydrogenase (SLD) content significantly is lower than the blank group.
Conclusion: breviscapine frozen dry powder of the present invention has the better protect effect to acute myocardial ischemia.Can reduce because the electrocardiogram S-T section that myocardial ischemia causes is raised, dwindle because the myocardial ischemia scope that infraction causes lowers serum lactate dehydrogenase (SLD) content.
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment.
Embodiment 1
Take by weighing breviscapine coarse powder 50g and pulverize, cross 10 mesh sieves.Add 70% soak with ethanol 24h, move in the percolator, with the speed percolation of 0.6mL/min, collect the 900mL percolate, being evaporated to does not have alcohol flavor (0.1MP, 60 ℃).Concentrated solution is by HPD-100 type macroporous adsorptive resins (400mL) purification, and with 4BV distilled water eluting, reuse 60% ethanol 6BV eluting is collected 60% ethanol elution earlier, and concentrating under reduced pressure (0.1MP, 60 ℃) gets extract to 100mL.
Extract adds 50g mannitol, and after the dissolving, add the injection water and make into 1000ml, ultrafiltration membrance filter (6000 molecular weight) degerming, under aseptic condition, fill is in the 5mL bottle (every bottled 2mL) of sterilizing, lyophilization.
Embodiment 2
Take by weighing breviscapine coarse powder 70g, with 95% alcohol reflux 3 times, the solvent consumption is 8 times, and extraction time is 1.5h, merges medicinal liquid, and being evaporated to does not have alcohol flavor (0.1MP, 60 ℃).Concentrated solution is by D101 type macroporous adsorptive resins (200mL) purification, and with 4BV distilled water eluting, reuse 30% ethanol 6BV eluting is collected 30% ethanol elution, and concentrating under reduced pressure (0.1MP, 60 ℃) is to 50mL earlier.Take by weighing Radix Notoginseng coarse powder 35g, with 70% alcohol reflux 3 times, the solvent consumption is 10 times, and extraction time is 1h, merges medicinal liquid, and being evaporated to does not have alcohol flavor (0.1MP, 60 ℃).Concentrated solution is by D101 type macroporous adsorptive resins (200mL) purification, and with 4BV distilled water eluting, reuse 70% ethanol 7BV eluting is collected 70% ethanol elution, and concentrating under reduced pressure (0.1MP, 60 ℃) is to 100mL earlier.Take by weighing Flos Carthami 45g, decoct with water three times, for the first time 1h, 50min for the second time, 30min for the third time, collecting decoction, filter, it is 1.15-1.21 that filtrate is concentrated into relative density, the same operation, collect 30% ethanol elution, and concentrating under reduced pressure (0.1MP, 60 ℃) is to 100mL, with the solution mix homogeneously, add the injection water and make into 1000ml, ultrafiltration membrance filter (6000 molecular weight) degerming, under aseptic condition, fill is in the 5mL bottle (every bottled 2mL) of sterilizing, lyophilization.
Embodiment 3
Take by weighing breviscapine 80g and add 80% soak with ethanol 24h, move in the percolator, with the speed percolation of 1mL/min, collect the 1000mL percolate, being evaporated to does not have alcohol flavor (0.1MP, 60 ℃).Concentrated solution is by AB-100 type macroporous adsorptive resins (400mL) purification, and with 4BV distilled water eluting, reuse 60% ethanol 6BV eluting is collected 60% ethanol elution earlier, and concentrating under reduced pressure (0.1MP, 60 ℃) gets extracting solution to 100mL.Under aseptic condition, fill is in the 5mL bottle (every bottled 2mL) of sterilizing, lyophilization, relieving disorders of the chest powder pin.
Embodiment 4
Take by weighing breviscapine coarse powder 45g, with 45% alcohol reflux 2 times, the solvent consumption be 5-8 doubly, extraction time is 1h, merges medicinal liquid, being evaporated to does not have alcohol flavor (0.1MP, 60 ℃).Concentrated solution is by D101 type macroporous adsorptive resins (200mL) purification, and with 4BV distilled water eluting, reuse 40% ethanol 6BV eluting is collected 40% ethanol elution, and concentrating under reduced pressure (0.1MP, 60 ℃) is to 60mL earlier.With the solution mix homogeneously, after the dissolving, add the injection water and make into 1000ml, ultrafiltration membrance filter (6000 molecular weight) degerming, under aseptic condition, fill is in the 5mL bottle (every bottled 2mL) of sterilizing, lyophilization.
Embodiment 5
It is an amount of to get the breviscapine medical material, pulverizes, and crosses 10 mesh sieves, add concentration 30% alcohol heating reflux 1h, leach medicinal liquid, medicinal residues are the same to be extracted once again, merge medicinal liquid, being evaporated to does not have alcohol flavor (0.1MP, 60 ℃), concentrated solution is by AB-8 type macroporous adsorbent resin (600mL) purification, with 4BV distilled water eluting, reuse 50% ethanol 6BV eluting is collected 50% ethanol elution earlier, and concentrating under reduced pressure (0.1MP, 60 ℃) is to 200mL.Again in concentrated solution, extract adds 15gPEG, and after the dissolving, add the injection water and make into 1000ml, ultrafiltration membrance filter (6000 molecular weight) degerming, under aseptic condition, fill is in the 5mL bottle (every bottled 2mL) of sterilizing, lyophilization.
Embodiment 6
Get breviscapine medical material 65g, pulverize, cross 10 mesh sieves, add concentration 65% alcohol heating reflux 1h, leach medicinal liquid, medicinal residues are the same to be extracted once again, merge medicinal liquid, being evaporated to does not have alcohol flavor (0.1MP, 60 ℃), concentrated solution is by HPD100 type macroporous adsorbent resin (500mL) purification, with 4BV distilled water eluting, reuse 50% ethanol 6BV eluting is collected 50% ethanol elution earlier, and concentrating under reduced pressure (0.1MP, 60 ℃) is to 100mL.Add the 25g glucose, after the dissolving, extract adds the injection water makes into 1000ml, ultrafiltration membrance filter (6000 molecular weight) degerming, and under aseptic condition, fill is in the 5mL bottle (every bottled 2mL) of sterilizing, lyophilization.
Claims (6)
1. injection breviscapine dry powder pin, it is made up of small cup florigen water solubility extract and pharmaceutical excipient.
2. freeze-dried powder as claimed in claim 1 is characterized in that being made up of following materials based on weight:
Breviscapine water solubility extract 10-100 part
Pharmaceutical excipient 2-30 part.
3. freeze-dried powder as claimed in claim 1 or 2 is characterized in that described pharmaceutical excipient is mannitol, glucose or lactose.
4. freeze-dried powder as claimed in claim 1 or 2 is characterized in that described breviscapine water solubility extract, is the ethanol extraction that adopts water or arbitrary proportion, concentrates, and through the macroporous adsorbent resin separation and purification, concentrates and makes.
5. the preparation method of a breviscapine dry powder pin comprises:
(1) get the breviscapine water solubility extract, add excipient, stirring and dissolving, medicinal liquid adds the injection water to certain volume, and by ultrafiltration membrance filter, fill; (2) according to pre-conditioned lyophilization, gland, packaging seal, promptly.
6. preparation method as claimed in claim 5 is characterized in that in freeze-drying process, and medicinal liquid keeps 2～8h down freeze-drying curve temperature descending section temperature low spot-10～-50 ℃, keeps 1～5h down for 0～40 ℃ at the high point of temperature rise period temperature.
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| Application Number | Priority Date | Filing Date | Title |
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| CN200810153363A CN101757068A (en) | 2008-11-25 | 2008-11-25 | Breviscapine frozen dry powder for injection and preparation method thereof |
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| CN200810153363A CN101757068A (en) | 2008-11-25 | 2008-11-25 | Breviscapine frozen dry powder for injection and preparation method thereof |
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| CN101757068A true CN101757068A (en) | 2010-06-30 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108078920A (en) * | 2018-02-27 | 2018-05-29 | 云南玉药生物制药有限公司 | A kind of Breviscapini injection preparation process of stabilization |
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- 2008-11-25 CN CN200810153363A patent/CN101757068A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108078920A (en) * | 2018-02-27 | 2018-05-29 | 云南玉药生物制药有限公司 | A kind of Breviscapini injection preparation process of stabilization |
| CN108078920B (en) * | 2018-02-27 | 2020-04-07 | 云南玉药生物制药有限公司 | Preparation process of stable breviscapine injection |
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Open date: 20100630 |