CN1943618A - Red sage root effective part standard extract and its preparing method and use - Google Patents
Red sage root effective part standard extract and its preparing method and use Download PDFInfo
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Abstract
The invention relates to extracting tanshinpropanone from the effective part of the root of red-rooted salvia and preparation thereof and application of medicinal compound from said extracting stuff in preparation of drugs for treatment and prevention for blood shortage disease of heart and brain. Process for tanshinpropanone is as follows, extracting tanshinone type compound by supercritical extracting technique of carbon dioxide, boiling with water and extracting soluble salvianolic acid type and purifying thereof through ethyl acetate, thereafter mixing these two solid powder obtained according to extracting rate and content converting.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation and its production and application; In particular, pharmaceutical composition and the application in preparation treatment ischemic cardiovascular and cerebral vascular disease medicine thereof that the present invention relates to red sage root effective part standard extract Radix Salviae Miltiorrhizae phenolic ketone, its preparation method and comprise described Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketone.
Background technology
The used crude drug Radix Salviae Miltiorrhizae of Radix Salviae Miltiorrhizae phenolic ketone is traditional conventional Chinese medicine, records in the People's Republic of China (PRC) and goes through in edition pharmacopeia, and relevant Chinese medicine universities and colleges teaching material, monograph and dictionary class Chinese medicine books all record introduction as the emphasis medicine.Radix Salviae Miltiorrhizae is the root of Labiatae salvia Salvia miltiorrhiza Bge..For a long time, Radix Salviae Miltiorrhizae is widely used in multiple treatment of diseases, is representational blood-activating and stasis-removing.Mainly contain diterpene quinones, phenolic acid compound in the Radix Salviae Miltiorrhizae, also contain tannin, polysaccharide etc. in addition.Diterpenoid tanshinone mainly contains Tanshinone I I A (Tanshinone II A), cryptotanshinone (Cryptotanshinone), Tanshinone I (Tanshinone I), dihydrotanshinone (Dihydrotanshinone), methyltanshinone (Methyltashinone) etc.; Phenolic acid compound mainly contains salvianolic acid B (Salvianolic acid B), salvianolic acid A (Salvianolic acid A), danshensu (Danshensu), rosmarinic acid (Rosmarinic acid), protocatechualdehyde (Protocatechualdehyde), protocatechuic acid (Protocatechuic acid), caffeic acid (Coffeic acid) and salvianolic acid C, D, E etc.Preparation as the Radix Salviae Miltiorrhizae single medicinal material has Radix Salviae Miltiorrhizae Tabellae, danshen cream, Danshen heart-benefiting sheet or the like.
Water-soluble phenolic acid compounds that Radix Salviae Miltiorrhizae mainly contains and fat-soluble diterpene quinone all are main effective ingredient of Radix Salviae Miltiorrhizae, it also is the main active of Treated with Radix Salviae Miltiorrhizae cardiovascular and cerebrovascular disease, because this two constituents character is all very unstable, the improper of extraction process can greatly influence product quality, the existing most technology of red sage formulation is not too perfect, the restive product quality of product standard, dose is also big, and " full effective ingredient " product to the main effect of energy authentic representative Radix Salviae Miltiorrhizae is not arranged as yet so far, system's pharmacology of can the authentic representative Radix Salviae Miltiorrhizae itself carrying out, the report of toxicologic study, therefore, existing Radix Salviae Miltiorrhizae security of products, effectiveness and quality controllability and homogeneity are all demanded urgently improving and are improved.
Radix Salviae Miltiorrhizae extraction process of the prior art is to adopt high concentration ethanol to extract its fat-soluble part, and reuse water extraction water-soluble portion is rational theoretically.But because Radix Salviae Miltiorrhizae fat, water-soluble portion composition all exists the thermally labile problem, thereby caused in the red sage formulation the main content of effective of Radix Salviae Miltiorrhizae usually low excessively, be difficult to guarantee curative effect of medication.The quality standard of red sage formulation is an index with Tanshinone I I A mostly in addition, therefore to the improvement research of Radix Salviae Miltiorrhizae extraction process, mainly concentrates on extraction and reservation to diterpene quinone; On the other hand, more and more evidences successively shows the salvia-soluble part, before this danshensu, after be salvianolic acid B and other phenolic acid, as salvianolic acid A, rosmarinic acid etc. all are important effective ingredient of Radix Salviae Miltiorrhizae cardiovascular and cerebrovascular vessel effect, thereby to the research of salvianolic acid constituents also day by day deeply and get along with.
Above-mentioned situation shows owing to technical elements, the technology of preparing and the product of the whole effective ingredient of energy authentic representative Radix Salviae Miltiorrhizae do not arranged as yet so far, and the quality standard that can really control this product inherent quality.Existing red sage formulation also be mainly used in cardiovascular disease and action temperature and.
Summary of the invention
It is Radix Salviae Miltiorrhizae phenolic ketone and preparation method thereof and quality control standard that the object of the invention is to provide a kind of standard extract that contains main effective site of Radix Salviae Miltiorrhizae and composition, and the pharmaceutical composition that comprises this standard extract, this pharmaceutical preparation has significant anti-cardiac-cerebral ischemia and function of promoting blood circulation to disperse blood clots, can represent the whole effects and the effect of Radix Salviae Miltiorrhizae, and its active component content height, stable homogeneous, efficacy strength increases substantially.
A kind of extracting method that extracts the salviol one compositions from the red rooted salvia raw material provided by the present invention, process combination is ingenious rationally, can increase substantially the rate of transform of Radix Salviae Miltiorrhizae fat, water solublity two effective constituents, thereby has the commercial production promotional value.
The present invention seeks to realize by following technical solution:
A kind of red sage root effective part standard extract that contains water-soluble phenolic acid compounds and fat-soluble diterpene quinone simultaneously provided by the invention, both gross weights account for the 50-100 weight % of extract gross weight, it is characterized in that: Radix Salviae Miltiorrhizae total phenols total amount accounts for the 40-95 weight % of this standard extract total amount, wherein mainly comprise salvianolic acid A, salvianolic acid B, rosmarinic acid, danshensu, protocatechualdehyde, wherein the content of salvianolic acid B is 0-80 weight %; The total ketone total amount of Radix Salviae Miltiorrhizae accounts for the 5-60 weight % of this standard extract total amount, wherein mainly comprises Tanshinone I I A, cryptotanshinone, Tanshinone I, and wherein Tanshinone I I A accounts for 0-20 weight %.
The preparation method of a kind of red sage root effective part standard extract provided by the invention, it is characterized in that this method comprises the steps: to extract tanshinone compound with the carbon dioxide supercritical fluid extraction technology, reuse water boiling and extraction water solublity salvianolic acid class and with the ethyl acetate purification, above-mentioned two compounds of carrying are purchased with identical crude drug amount mixed by its yield and are got.
The extracting method of a kind of red sage root effective part standard extract provided by the invention is characterized in that this method comprises the steps:
(1) extraction of Radix Salviae Miltiorrhizae ester soluble components
Only making the back red rooted salvia broken is coarse powder, adopts liquid CO in supercritical extraction (SFE) device
2Extract fat soluble ingredient of red sage root, extraction conditions is: pressure: 10-40MPa, and temperature 20-65 ℃ is entrainer with 50-100 weight % ethanol, the entrainer consumption is a 4-10 times of medical material amount, extraction time 2-8 hour.Extract is pulverized, promptly through vacuum drying below 60 ℃.
In the above-mentioned steps, extracting the total ketone yield of Radix Salviae Miltiorrhizae that obtains is 0.8-4.8 weight %, and content is 30-80 weight %, and wherein Tanshinone I I A content is 8-40 weight %; The retention rate of the total ketone of Radix Salviae Miltiorrhizae is 〉=80 weight %, the retention rate of Tanshinone I I A 〉=80 weight %;
(2) extraction and purification of red sage root water soluble ingredient
Get the Radix Salviae Miltiorrhizae medicine residue that step 1 obtains, extract phenolic acid compound with conventional extraction process by water, extraction conditions is: the water yield of adding is 10 times of medical material amount, decocts and extracts 2-3 time, each 1 hour, extracts 80-100 ℃ of temperature.
In the above-mentioned steps, the Radix Salviae Miltiorrhizae total phenolic acids and the salvianolic acid B rate of transform 〉=80 weight %;
With the Radix Salviae Miltiorrhizae water extract that obtains, through being concentrated into 2-4g crude drug/ml, directly extract with ethyl acetate, extraction conditions is: pH value is 1-4, and extraction time is 2-8 time, extraction time is 5-60 minute, each amount that adds ethyl acetate is that Radix Salviae Miltiorrhizae extracts 2 times that concentrate liquid measure, and extracting solution reclaims ethyl acetate, drying, pulverize, promptly.
In the above-mentioned steps, the rate of transform of Radix Salviae Miltiorrhizae total phenols is 〉=70 weight %, and content is 〉=70 weight %; The salvianolic acid B rate of transform 〉=65 weight %, content 〉=35 weight %;
(3) acquisition of red sage root effective part standard extract (Radix Salviae Miltiorrhizae phenolic ketone)
The total ketone of Radix Salviae Miltiorrhizae that obtains through above-mentioned technology and two kinds of pressed powders of Radix Salviae Miltiorrhizae total phenols are converted to respect to primary dose by its extraction ratio and content and mix, and promptly get red sage root effective part standard extract Radix Salviae Miltiorrhizae phenolic ketone.
The present invention also provides a kind of pharmaceutical composition that contains above-mentioned red sage root effective part standard extract Radix Salviae Miltiorrhizae phenolic ketone, it is characterized in that described compositions comprises pharmaceutically acceptable carrier, be made into the outstanding agent of powder, tablet, capsule, granule, oral liquid, drop pill, oral cavity disintegration tablet, stomach, suppository, and exterior-applied formulation and preparation capable of permeating skin such as patch, medicated wine, liniment.
Aforementioned pharmaceutical compositions is characterized in that described pharmaceutical composition can use separately, perhaps with similar activity or auxilliary mutually active medication combined use are arranged to heighten the effect of a treatment, enlarge therapeutic domain.
The present invention also provides the application of red sage root effective part standard extract in the medicine of preparation treatment ischemic cardiovascular and cerebral vascular disease.
Compare with the existing extraction process that contains the red sage formulation of Radix Salviae Miltiorrhizae single active component, the present invention has following advantage:
1, compares with commercially available single red sage formulation and the main red sage compound preparation of using prior art for preparing, use the Radix Salviae Miltiorrhizae phenolic ketone sheet of the technology of the present invention prepared and want high a lot of by content of effective such as the contained Radix Salviae Miltiorrhizae total phenols of commensurability crude drug, the total ketone of Radix Salviae Miltiorrhizae, salvianolic acid B, tanshinones, therefore act on also much better thanly, Radix Salviae Miltiorrhizae phenolic ketone preparation of the present invention can be obtained more significant curative effect in the scope that keeps former Radix Salviae Miltiorrhizae and red sage formulation consumption per day.
2, drug efficacy study shows; the commercially available Radix Salviae Miltiorrhizae Tabellae of producing with prior art, the people of red sage formulation obey crude drug daily dose reduced value and compare; the action intensity of effects such as the anti-cardiac-cerebral ischemia of Radix Salviae Miltiorrhizae phenolic ketone preparation of the present invention is better than the Radix Salviae Miltiorrhizae Tabellae that prior art is produced at double; ischemia injury to brain also has the good protection effect, and toxicologic study shows that Radix Salviae Miltiorrhizae phenolic ketone of the present invention and preparation thereof have good safety.
3, compare with existing red sage formulation, Radix Salviae Miltiorrhizae phenolic ketone preparation of the present invention, as Radix Salviae Miltiorrhizae phenolic ketone sheet with the quantitative assay index of Radix Salviae Miltiorrhizae total phenols, the total ketone of Radix Salviae Miltiorrhizae, salvianolic acid B, four materials of tanshinone as the quality control main standard, overcome existing red sage formulation only with the defective of single component as quality control standard, thereby Radix Salviae Miltiorrhizae phenolic ketone of the present invention and preparation thereof be control of quality really, quality standard is comprehensive and high, can guarantee the stable homogeneous of product quality.
4, compare with existing effective component in red sage extracting method, the present invention fully takes into account the physicochemical property of Radix Salviae Miltiorrhizae phenols and this two constituents of tanshinone, and invented a kind of more rational effective component in red sage extracting method technology, the rate of transform of this two constituents in preparation increased substantially than current technology, and have short, easy to operate, the high product quality advantages of the flow process of extraction.
The specific embodiment
The following examples are only in order to illustrate the present invention, rather than in order to limit protection scope of the present invention.
Embodiment 1: the method for extracting Danshen effective component (Radix Salviae Miltiorrhizae phenolic ketone) from the raw material Radix Salviae Miltiorrhizae
Used red rooted salvia is purchased in market or Radix Salviae Miltiorrhizae GAP production base in the inventive method, and device therefor is field of traditional Chinese medicine pharmacy extraction process equipment commonly used, and the carbon dioxide supercritical fluid extraction device can be made by oneself, or buys finished product from the city.
Radix Salviae Miltiorrhizae phenolic ketone extracting method of the present invention is: extract tanshinone compound with the carbon dioxide supercritical fluid extraction technology, reuse water boiling and extraction water solublity salvianolic acid class and with the ethyl acetate purification.This technology makes the rate of transform of two constituents in standard extract and preparation thereof increase substantially than current technology, the mean transferred rate Radix Salviae Miltiorrhizae total phenols of five batches of pilot scales is 73.93%, salvianolic acid B is 66.87%, and the total ketone of Radix Salviae Miltiorrhizae is 88.23%, and Tanshinone I I A is 87.38%.Thereby can guarantee the action intensity and the clinical efficacy of Radix Salviae Miltiorrhizae phenolic ketone and preparation thereof.
The concrete steps of the extracting method of Danshen effective component extract of the present invention (Radix Salviae Miltiorrhizae phenolic ketone) are as follows:
(1) extraction of Radix Salviae Miltiorrhizae ester soluble components (the total ketone of Radix Salviae Miltiorrhizae)
Only making the back red rooted salvia broken is coarse powder, adopts liquid CO in the SFE device
2Extract fat soluble ingredient of red sage root, extraction conditions is: pressure: 20MPa, and 40 ℃ of temperature are entrainer with 95% ethanol, the entrainer consumption is 8 times of medical material amounts, extraction time 6h.
By 80 kilograms of the above-mentioned conditions/5 batches of pilot scales that batch feed intake carry the total ketone yield of Radix Salviae Miltiorrhizae average out to 1.46%, content is 46.68%, wherein Tanshinone I I A content is 13.39%.The retention rate of the total ketone of Radix Salviae Miltiorrhizae is 88.7%, the retention rate 87.4% of Tanshinone I I A.If increase extraction time, also can further improve the rate of transform of total ketone of Radix Salviae Miltiorrhizae and Tanshinone I I A.
(2) extraction and purification of red sage root water soluble ingredient (salvianolic acid)
The salvia-soluble effective ingredient is mainly phenolic acid compound, gets the residue behind the above-mentioned fat soluble ingredient of red sage root extraction step, adopts conventional extraction process by water, the rate of transform about 90%, and cost is low, easy to operate, safety.
The condition of extraction process by water is: the water yield that medicinal residues add is 10 times of medical material amount, decocts and extracts 2-3 time, and each 1 hour, this moment, Radix Salviae Miltiorrhizae total phenolic acids and salvianolic acid B retention rate were more than 88%.If extraction time is increased to 3～4 times, retention rate also can increase by 8～10% again.
Get the above-mentioned Radix Salviae Miltiorrhizae water extract for preparing, concentrate the back and adopt ethyl acetate directly to extract, extraction conditions is: pH value is 2.5, and it is 4 times that ester is carried number of times, and extraction time is 20 minutes, and the amount that at every turn adds ethyl acetate is 2 times that Radix Salviae Miltiorrhizae concentrates liquid measure.The rate of transform of each effective ingredient of salvia-soluble is all greater than more than 60% behind the ethyl acetate extraction purification, and the percentage composition also high (＞60%) of total phenolic acid, can reach predetermined purification purpose.
The rate of transform of Radix Salviae Miltiorrhizae total phenols is 73.75%, and content is 74.80%; The salvianolic acid B rate of transform 66.90%, content 42.20%.Increase ethyl acetate extraction purification number of times, the rate of transform also can further improve.
(3) preparation of standard extract Radix Salviae Miltiorrhizae phenolic ketone
Get Radix Salviae Miltiorrhizae SFE extract and adopt vacuum dehydrating at lower temperature, water intaking-ethyl acetate extract adopts spray drying, obtains to mix for identical crude drug amount ratio in the extraction ratio conversion behind two kinds of pressed powders, is the effective part standard extract Radix Salviae Miltiorrhizae phenolic ketone of Radix Salviae Miltiorrhizae.
Adopt method for preparing to obtain red sage root effective part standard extract Radix Salviae Miltiorrhizae phenolic ketone, it is made up of water-soluble phenolic acids extract and fat-soluble diterpene quinones extract, can record two compounds total amounts by content assaying method and account for more than 50% of extract gross weight (surpassing 65%), wherein Radix Salviae Miltiorrhizae total phenols total amount accounts for more than 40% of extract gross weight, mainly comprise salvianolic acid A, salvianolic acid B, rosmarinic acid, danshensu, protocatechualdehyde etc., wherein the content of salvianolic acid B is about 80% of Radix Salviae Miltiorrhizae total phenols amount; The total ketone total amount of Radix Salviae Miltiorrhizae accounts for more than 10% of extract weight, and wherein Tanshinone I I A accounts for more than 2%.
Embodiment 2 contains the preparation of the tablet of Radix Salviae Miltiorrhizae phenolic ketone
Get Radix Salviae Miltiorrhizae phenolic ketone 100g, pregelatinized Starch 50g, carboxymethyl starch sodium 26.4g, cross 60 mesh sieves and be mixed to evenly, add dehydrated alcohol and make soft material in right amount, 18 mesh sieves are granulated, 40 ℃ of dryings, add carboxymethyl starch sodium 17.6g, magnesium stearate 2g behind the 18 mesh sieve granulate, mixing is compressed to 1000, get label (plain sheet), promptly get Radix Salviae Miltiorrhizae phenolic ketone Film coated tablets with 8% film coating pre-mix dose alcoholic solution coating in coating pan, the heavy 250mg of sheet includes Radix Salviae Miltiorrhizae phenolic ketone 100mg.
The composition measurement and the quality control of embodiment 3 Radix Salviae Miltiorrhizae phenolic ketones and Radix Salviae Miltiorrhizae phenolic ketone sheet
Be control of quality effectively, we analyze extracting product Radix Salviae Miltiorrhizae phenolic ketone and Radix Salviae Miltiorrhizae phenolic ketone sheet.With Radix Salviae Miltiorrhizae total phenolic acids, salvianolic acid B, the total ketone of Radix Salviae Miltiorrhizae, Tanshinone I I A is main quantitatively quality control index, and mentioned component is used UV respectively and the HPLC method is measured, and formulates the quality inspection index according to concrete testing result, sees Table 1.
Table 1 Radix Salviae Miltiorrhizae phenolic ketone mainly contains imitates position composition quality index
| The total ketone of Radix Salviae Miltiorrhizae | Tanshinone | The Radix Salviae Miltiorrhizae total phenols | Salvianolic acid B | |
| Medical material (%) Radix Salviae Miltiorrhizae phenolic ketone (%) Radix Salviae Miltiorrhizae phenolic ketone every amount of sheet (mg) day dosing (mg) | ≥0.45 ≥8 8 48 | ≥0.2 ≥2.5 2.5 15 | ≥4.5 ≥50 50 300 | ≥3.0 ≥30 30 180 |
Embodiment 4 Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketones are to the influence of dog acute myocardial ischemia model
Pharmacodynamic study is the result show, Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketone of the present invention causes on the dog acute myocardial ischemia model in the ligation anterior descending coronary, Radix Salviae Miltiorrhizae phenolic ketone 40,80,160mg/kg can obviously improve the degree of ischemia of epicardial electrogram mapping, wherein middle and high dosage group descend respectively 37.1 ± 10.1% (P＜0.01), 55.2+7.2% (P＜0.01); The ischemia scope also has in various degree dwindles; Myocardial infarct size has then dwindled 21.0% (P＞0.05), 35.5% (P＜0.001), 60.4% (P＜0.001) respectively; High dose can also obviously suppress the rising of Serum LDH-L cardiac muscle isozyme level; Middle and high dosage can reduce myocardial oxygen consumption; Radix Salviae Miltiorrhizae phenolic ketone 80mg/kg function of resisting myocardial ischemia and 480mg/kg Radix Salviae Miltiorrhizae Tabellae (commercially available) are suitable.
Rats gavaged Radix Salviae Miltiorrhizae phenolic ketone extract 100,200,400mg/kg every day 1 time, continuous 5 days, can suppress in various degree because of the anterior descending coronary ligation causes raising of II lead electrocardiogram ST section, 5～60min onset is kept more than the 180min; Can obviously dwindle myocardial infarct size, infarcted region/hazardous area has reduced by 39.2% (P＜0.01), 50.0% (P＜0.001), 57.3% (P＜0.001) respectively; Can obviously suppress serum myocardium enzyme level and raise, AST has suppressed 17.7% (P＞0.05), 41.5% (P＜0.001), 48.1% (P＜0.01) respectively; LDH has suppressed 32.3% (P＞0.05), 48.5% (P＜0.01), 62.6% (P＜0.001) respectively; CK-MB raises and has suppressed 43.3% (P＜0.05), 50.9% (P＜0.01), 76.3% (P＜0.001) respectively.Its 200mg/kg function of resisting myocardial ischemia and 1200mg/kg Radix Salviae Miltiorrhizae Tabellae (commercially available) are suitable.
Rat every day 1 time, gavaged Radix Salviae Miltiorrhizae phenolic ketone 100,200,400mg/kg in continuous 5 days, can suppress the platelet aggregation that multiple derivant causes, the inductive gathering suppression ratio of adenosine diphosphate (ADP) (ADP) is respectively 24.8% (P＜0.05), 35.6% (P＜0.001), 45.7% (P＜0.001); The inductive gathering suppression ratio of arachidonic acid (AA) is respectively 29.0% (P＜0.05), 57.4% (P＜0.001), 72.3% (P＜0.001); The inductive gathering suppression ratio of collagen (CG) is respectively 14.6% (P＞0.05), 20.6% (P＜0.01), 34.3% (P＜0.01); The experimental artery thrombosis time that the damage of electricity irritation carotid artery intima is caused prolongs 6.5% (P＞0.05), 16.8% (P＜0.05), 21.7% (P＜0.01) respectively; Can also obviously reduce whole blood and the plasma viscosity of the hemorheology rat that macromolecule right rotary glycoside causes.Its 200mg/kg function of promoting blood circulation to disperse blood clots and 1200mg/kg Radix Salviae Miltiorrhizae Tabellae (commercially available) are suitable.
Embodiment 5 Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketones are to the influence of dog acute myocardial ischemia model
Pharmacodynamic study is the result show, Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketone of the present invention is on the global brain ischemia model, every day 1 time, gavaged Radix Salviae Miltiorrhizae phenolic ketone 100,200 in continuous 5 days, 400mg/kg can suppress the bilateral ligation legal system and be equipped with global brain ischemia rat model brain water content, increase ischemia brain SOD activity, reduce the unusual MDA content that raises; Acute focal cerebral ischemia model (MCAO) the rat ischemia side cerebral tissue Infarction volume that suppresses the preparation of middle cerebral artery embolization simultaneously accounts for the percentage rate of half side cerebral tissue, function of nervous system's infringement scoring behind the reduction cerebral ischemia re-pouring.Compare with matched group, the brain water content increase has reduced by 22.5% (P＜0.05), 34.6% (P＜0.05) and 56.3% (P＜0.01) respectively; SOD has increased by 32.6% (P＜0.05), 44.8% (P＜0.01) and 62.3% (P＜0.01) respectively; MDA content increases and has suppressed 48.3% (P＜0.01), 59.2% (P＜0.01) and 74.8% (P＜0.01); The cerebral infarction volume ratio has reduced by 18.2% (P＞0.05), 25.6% (P＜0.05) and 36.5% (P＜0.01) respectively; Nervous function damage scoring has reduced by 20.8% (P＜0.05), 31.2% (P＜0.01) and 42.3% (P＜0.01) respectively, the anti-cerebral ischemia of 200mg/kg Radix Salviae Miltiorrhizae phenolic ketone and ischemical reperfusion injury effect approximately with the effect of 1200mg/kg Radix Salviae Miltiorrhizae Tabellae quite or slightly strong.
Above-mentioned pharmacodynamic study result shows: Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketone of the present invention has obvious anti-cardiac-cerebral ischemia effect and function of promoting blood circulation to disperse blood clots, and its effect amount-result relation is clear and definite, and action intensity greatly surpasses the commercially available Radix Salviae Miltiorrhizae Tabellae that prior art is produced.
The toxicity research of embodiment 6 Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketones
Mice and rat acute toxicity test Radix Salviae Miltiorrhizae phenolic ketone 8g/kg gavage no overt toxicity reaction, rat successive administration June, 9 months long term toxicity test of dog successive administration, and the animal general pharmacology is learned result of study and is shown that all Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketone of the present invention does not have overt toxicity.Situation in conjunction with Radix Salviae Miltiorrhizae and the clinical prolonged application of preparation thereof are not seen overt toxicity illustrates that Radix Salviae Miltiorrhizae standard extract Radix Salviae Miltiorrhizae phenolic ketone has big safety.
The comparison of embodiment 7 Radix Salviae Miltiorrhizae phenolic ketone tablets and commercially available Radix Salviae Miltiorrhizae Tabellae
Radix Salviae Miltiorrhizae phenolic ketone sheet of the present invention is compared with the commercially available Radix Salviae Miltiorrhizae Tabellae that prior art is produced, and the amount of the active component of Radix Salviae Miltiorrhizae phenolic ketone tablet of the present invention is calculated by day for human beings dosing and improved a lot, and comparative result sees Table 2.
Table 2 Radix Salviae Miltiorrhizae phenolic ketone sheet and commercially available Radix Salviae Miltiorrhizae Tabellae per diem dosing calculate dosing of main effective ingredient day of Radix Salviae Miltiorrhizae (mg/d) relatively
| The name of an article | Suitable crude drug (g/d) | The total ketone of Radix Salviae Miltiorrhizae (mg/d) | Tanshinone I I A (mg/d) | Radix Salviae Miltiorrhizae total phenols (mg/d) | Radix Salviae Miltiorrhizae acid B (mg/d) |
| The commercially available Danshen heart-benefiting capsule of the commercially available DANSHEN KELI of the commercially available Radix Salviae Miltiorrhizae Tabellae of Radix Salviae Miltiorrhizae phenolic ketone sheet | 8 12 30 | 48 35 0 17 | 15 7.3 0 4.7 | 300 191 262 121 | 180 90 69 62 |
Claims (9)
1, a kind of red sage root effective part standard extract that contains water-soluble phenolic acid compounds and fat-soluble diterpene quinone simultaneously, both gross weights account for the 50-100 weight % of extract gross weight, it is characterized in that: Radix Salviae Miltiorrhizae total phenols total amount accounts for the 40-95 weight % of this standard extract total amount, wherein mainly comprise salvianolic acid A, salvianolic acid B, rosmarinic acid, danshensu, protocatechualdehyde, wherein the content of salvianolic acid B is 0-80 weight %; The total ketone total amount of Radix Salviae Miltiorrhizae accounts for the 5-60 weight % of this standard extract total amount, wherein mainly comprises Tanshinone I I A, cryptotanshinone, Tanshinone I, and wherein Tanshinone I I A accounts for 0-20 weight %.
2, a kind of preparation method of red sage root effective part standard extract, it is characterized in that this method comprises the steps: to extract tanshinone compound with the carbon dioxide supercritical fluid extraction technology, reuse water boiling and extraction water solublity salvianolic acid class and with the ethyl acetate purification, above-mentioned two compounds of carrying are purchased with identical crude drug amount mixed by its yield and are got.
3, extracting method as claimed in claim 2 is characterized in that this method comprises the steps:
(1) extraction of Radix Salviae Miltiorrhizae ester soluble components
Only making the back red rooted salvia broken is coarse powder, adopts liquid CO in the SFE device
2Extract fat soluble ingredient of red sage root, extraction conditions is: pressure: 10-40MPa, and temperature 20-65 ℃ is entrainer with 50-100% ethanol, the entrainer consumption is a 4-10 times of medical material amount, extraction time 2-8 hour;
(2) extraction and purification of red sage root water soluble ingredient
Get the residue that step 1 obtains, extract phenolic acid compound with conventional extraction process by water, extraction conditions is: the water yield of adding is 10 times of medical material amount, decocts and extracts each 1 hour 2-3 time; With the Radix Salviae Miltiorrhizae water extract that obtains, after concentrating, directly extract with ethyl acetate, extraction conditions is: pH value is 1-4, and extraction times is 2-8 time, and the extraction time is 5-60 minute, and the amount that at every turn adds ethyl acetate is 2 times of concentrated liquid measure;
(3) prepare the method for Radix Salviae Miltiorrhizae phenolic ketone extract
Get Radix Salviae Miltiorrhizae SFE extract, adopt vacuum dehydrating at lower temperature, pulverize; Water intaking-ethyl acetate extract adopts spray drying; Two kinds of pressed powders that obtain mix for identical primary dose by extraction ratio and content conversion again, promptly get red sage root effective part standard extract Radix Salviae Miltiorrhizae phenolic ketone.
4, a kind of red sage root effective part standard extract for preparing with the described method of claim 3.
5, a kind of pharmaceutical composition that contains red sage root effective part standard extract described in claim 1 or 4 is characterized in that described compositions comprises pharmaceutically acceptable carrier.
6, pharmaceutical composition as claimed in claim 5 is characterized in that described pharmaceutical composition can use separately, perhaps with similar activity or auxilliary mutually active medication combined use are arranged.
7, pharmaceutical composition as claimed in claim 5 is characterized in that described pharmaceutical composition can be mixed with the dosage form of the pharmaceutical preparation of oral administration, coelenteron administration, spray delivery, ejection preparation, infusion preparation and Transdermal absorption.
8, pharmaceutical composition as claimed in claim 7 is characterized in that described oral administered dosage form is selected from: tablet, capsule, powder, granule, crystal, solution, suspension, soup, syrup, elixir, tea and masticatory.
9, the application of red sage root effective part standard extract in preparation treatment ischemic cardiovascular and cerebral vascular disease medicine described in claim 1 or 4, comprise the heart, cerebral ischemia diseases, the heart, cerebral ischemic reperfusion disease, the heart, cerebral infarction or embolism class diseases, and other be concerned about mutually, cerebrovascular disease.
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| CN101757105B (en) * | 2010-02-23 | 2012-05-23 | 广州汉方现代中药研究开发有限公司 | Extraction method capable of enriching fat soluble and water soluble parts of salvia simultaneously |
| CN101265286B (en) * | 2008-04-22 | 2012-06-06 | 美晨集团股份有限公司 | Method for separating and enriching cryptotanshinone from red sage root |
| CN102552398A (en) * | 2012-02-24 | 2012-07-11 | 山东大学 | Medicinal composition of radix salviae miltiorrhizae extract and application thereof |
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| WO2014201994A1 (en) * | 2013-06-17 | 2014-12-24 | 天士力制药集团股份有限公司 | Salvia miltiorrhiza extract, micropellet formulation thereof, methods of preparing same, and uses thereof |
| CN107582628A (en) * | 2017-08-30 | 2018-01-16 | 河南中医药大学 | Red sage root flower extract is preparing the application in treating transient cerebral ischemia syndrome medicament |
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| CN109596754A (en) * | 2018-07-05 | 2019-04-09 | 广州卡马生物科技有限公司 | A kind of Radix Salviae Miltiorrhizae reference extract and its application |
| CN111297943A (en) * | 2019-12-26 | 2020-06-19 | 闽江学院 | Supercritical CO2Application of fluid extraction of salvia miltiorrhiza extract |
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| CN101265286B (en) * | 2008-04-22 | 2012-06-06 | 美晨集团股份有限公司 | Method for separating and enriching cryptotanshinone from red sage root |
| CN101757105B (en) * | 2010-02-23 | 2012-05-23 | 广州汉方现代中药研究开发有限公司 | Extraction method capable of enriching fat soluble and water soluble parts of salvia simultaneously |
| CN102552398A (en) * | 2012-02-24 | 2012-07-11 | 山东大学 | Medicinal composition of radix salviae miltiorrhizae extract and application thereof |
| CN102793744A (en) * | 2012-08-24 | 2012-11-28 | 湖南恒伟药业股份有限公司 | Preparation method for blood-activation stasis-dissipation orifices-opening pain-relieving traditional Chinese medicine composition |
| WO2014201994A1 (en) * | 2013-06-17 | 2014-12-24 | 天士力制药集团股份有限公司 | Salvia miltiorrhiza extract, micropellet formulation thereof, methods of preparing same, and uses thereof |
| EA033184B1 (en) * | 2013-06-17 | 2019-09-30 | Тасли Фармасьютикал Груп Ко., Лтд. | Salvia miltiorrhiza extract, micropellet formulation thereof, micropellet capsule formulation therefrom, methods of preparation and use thereof |
| CN107582628A (en) * | 2017-08-30 | 2018-01-16 | 河南中医药大学 | Red sage root flower extract is preparing the application in treating transient cerebral ischemia syndrome medicament |
| CN109596754A (en) * | 2018-07-05 | 2019-04-09 | 广州卡马生物科技有限公司 | A kind of Radix Salviae Miltiorrhizae reference extract and its application |
| CN109010802A (en) * | 2018-09-21 | 2018-12-18 | 珠海汉盈科技有限公司 | The spontaneous hotting mask of promotion burn wound reparation containing Salvia root P.E |
| CN111297943A (en) * | 2019-12-26 | 2020-06-19 | 闽江学院 | Supercritical CO2Application of fluid extraction of salvia miltiorrhiza extract |
| CN112402314A (en) * | 2020-11-21 | 2021-02-26 | 浙江中医药大学 | Traditional Chinese medicine nourishing lipstick containing red sage root diterpene quinone and preparation method thereof |
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