CN1268319C - Rhodiola sacra injection and its preparation - Google Patents
Rhodiola sacra injection and its preparation Download PDFInfo
- Publication number
- CN1268319C CN1268319C CN 200410037408 CN200410037408A CN1268319C CN 1268319 C CN1268319 C CN 1268319C CN 200410037408 CN200410037408 CN 200410037408 CN 200410037408 A CN200410037408 A CN 200410037408A CN 1268319 C CN1268319 C CN 1268319C
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- concentrated
- concentrated solution
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- ethanol
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention discloses an extract of active ingredients of rhodiola sacra and a preparation method thereof. The extract of the active ingredients mainly contains salidroside, tyrosol, total flavonoids and polysaccharide. The present invention also discloses an injection preparation which uses the extract of the active ingredients of rhodiola sacra as principal raw materials and a preparing method thereof. The rhodiola sacra is extracted by a water extraction and precipitation method, or an alcohol backwashing method and a water extraction method, and concentrated solutions which comprises the extract of active parts are obtained; the pH value of the concentrated solutions is adjusted, and the concentrated solutions are placed in a still way and filtered; then, filtrates are put in a sterile siling bottle after filtered or ultrafiltered, the filtrates in the siling bottle are refrigerated and dried, the siling bottle is sealed by a pressed cock, and the injection preparation is obtained. Compared with the existing preparation formulation, the injection preparation of the present invention has the advantages that the action is direct, the effect is fast, symptoms can be controlled within a short time, and the present invention facilitates clinical emergency treatment.
Description
Technical field
The present invention relates to a kind of injection formulation and preparation method thereof, particularly relating to a kind of effective component extracts with Radix Rhodiolae is injection formulation of primary raw material and preparation method thereof, belongs to medical technical field.
Background technology
Radix Rhodiolae (RHODIOLA) is the Crassulaceae Rhodida plant, and Tibetan language claims " Suluomabu ".Be renascent herb or shrub plant, because of it contains red pigment, root and rhizome takes on a red color, and immersion also takes on a red color, and is again the Crassulaceae plant, so the name Radix Rhodiolae.Be distributed in high and cold areas such as former Soviet Union the Far East Area and Northeast China, northwest, southwest, about height above sea level 1500-4000 rice.The whole world is kind more than 90, and China's Radix Rhodiolae kind is many, and wild abundant information has 72 kinds.Radix Rhodiolae feeble QI perfume (or spice), bitter in the mouth, puckery, cold; Heat-clearing and toxic substances removing, dampness are used for lung-heat, arteries and veins heat, pestilence, limb edema.Tibetan medicine record: invigorate blood circulation, stop blooding, regulate the flow of vital energy nourish blood, strengthening the body resistance, nourishing the brain and improving intelligence, nourishing and fit keeping function.Medical book among the people record: property is flat, puckery, kind lung moistening, the kidney invigorating, strengthening the body resistance is arranged, regulate the flow of vital energy foster the spirit of nobility, the effect of brain healthy.Be usually used in senile heart failure, tired out, sexual impotence, diabetes, liver disease.Through medical expert's physico-chemical analysis and Instrumental Analysis both at home and abroad, kind of chemical compound surplus Radix Rhodiolae contains 40 mainly contains 21 kinds of the microelements of calcium, magnesium, ferrum, lead, zinc, silver, cobalt, cadmium, molybdenum, titanium, radium etc. of glycoside (rhodioloside, Arbutin, Lu Ding glycoside etc.), flavonoid (Quercetin, kaempferol anthocyanin etc.), Coumarins, Radix Rhodiolae polysaccharide class, biologically active.Also have needed tens seed amino acids of human body, wherein several is that human body is necessary and can not synthetic aminoacid in the body, also contains abundant vitamin.Modern medicine study is found: Radix Rhodiolae is that the environmental suitability medicine is received better curative effect on military medicine, aerospace medicine, sports medical science.Its critical function has: anti-hypoxia, resisting fatigue, the two-ways regulation to nervus centralis, delaying senility function, antitoxic action, radiation resistance and protective effect on cancer risk, to dual regulation of hormonal system etc.
The effective constituent that mainly contains that Radix Rhodiolae is found at present is rhodioloside, butyl alcohol, Radix Rhodiolae polysaccharide etc., and especially glycoside compound only contains C, H, three kinds of elements of O, and oxygen element elecrtonegativity center has more than two, and this compounds low toxicity, side effect is little but of many uses.Studying now by modern pharmacy, the Radix Rhodiolae of clear and definite substantially contained chemical constituent has following several:
1, slender lobule Radix Rhodiolae (Rhodiola heuryi) chemical analysis: succinic acid, gallic acid, tricin, tricin-7-oxygen-β-D-glycoside, daucosterol etc.
2, Rhodiola rosea L. (Rhodiola rosca) chemical constituent: rhodioloside, butyl alcohol, gallic acid, gallic acid formicester, cupreol, Rosavin etc.
3, Tang Gute Radix Rhodiolae (Rhodiola algida) chemical constituent: butyl alcohol, rhodioloside, gallic acid etc.
4, Radix Rhodiolae (Rhodiola sachalinensis) chemical constituent: rhodioloside, butyl alcohol, polyphenol etc.
5, Radix Rhodiolae (Rhodiola s era) chemical constituent: rhodioloside, caffeic acid, butyl alcohol, gallic acid, gallic acid second fat, cupreol, daucosterol etc.
6, Radix Rhodiolae (Rhodiola crenulata) chemical constituent: rhodioloside, butyl alcohol, the acid of burnt comb, gallic acid, cupreol, crenulatin etc.
7, Rhodiola kirilowii (Regel) Maxim. (Rhodiola kirilowii) chemical constituent: rhodioloside, butyl alcohol, cupreol.
8, long whip Radix Rhodiolae (Rhodiola fassiglea S.H.Fu) chemical constituent: cupreol, daucosterol, gallic acid, gallic acid second fat, butyl alcohol, cupreol-3-β-D-galactoside, the Arabic glucoside of herbaceous stem element-8-etc.
Now it is reported be used for medicine or health product mostly be Radix Rhodiolae, storehouse page or leaf Radix Rhodiolae (Radix Rhodiolae), Rhodiola kirilowii (Regel) Maxim., dark red Radix Rhodiolae etc., taken in one one of Pharmacopoeia of the People's Republic of China version in 1997 as rhodiola kirilowii Regel, Radix Rhodiolae is taken in " Tibetan medicine standard ".Research to Radix Rhodiolae class medicine also mainly is at above several, and is grown in rare correlational study of Radix Rhodiolae and report between the height above sea level 3500-5000 rice.First medical science ancient books and records of Ancient Times in China Shennong's Herbal is top grade with regard to already Radix Rhodiolae being classified as in the medicine in fact, and " main supporting ordered with Ying Tian, and be nontoxic, obeys clothes of a specified duration more and do not hurt sb.'s feelings." effect of " QI invigorating of making light of one's life by commiting suicide, do not prolong life always " arranged.In addition, in Tibetan medicine's masterpiece Four-Volume Medical Code and " month king medicine treasure " and " brilliant pearl book on Chinese herbal medicine " also relevant for the record of Radix Rhodiolae.In 8th century of Christian era, the Tibetan medicine cures the Four-Volume Medical Code record that the appropriate first Dan Gongbu of holy space writes: " property is flat, puckery, kind lung moistening, can the kidney invigorating, regulate the flow of vital energy and nourish blood.Cure mainly diseases such as the whole body is weak, uncomfortable in chest, nauseating, body void."; " brilliant pearl book on Chinese herbal medicine " record: " Radix Rhodiolae is invigorated blood circulation, and lung heat clearing, cough-relieving are brought down a fever, pain relieving, be used for the treatment of pneumonia, tracheitis, physical weakness, malaise, uncomfortable in chest, be difficult to breathe freely, lip and the palm of the hand be blue." use clinically at present with Radix Rhodiolae as primary raw material product forms tablet, hard capsule, oral liquid, granule etc. are only arranged, be used for the treatment of symptoms such as the thoracic obstruction due to the angina pectoris, uncomfortable in chest, chest pain clinically.Still the injection type that no stability is good, effect is direct, rapid-action, bioavailability is high.Existing peroral dosage form is the crude extract preparation of Radix Rhodiolae, contain excipient, required time of disintegrate is longer in vivo, onset is slow, the medication cycle is long, can't be at short notice effective controlling symptoms, it is slow to satisfy the needs onset of disease controlling in a short time clinically, the medication cycle is long, urgency, serious symptom but angina pectoris is fallen ill usually, as can't be at short notice effective controlling symptoms, just be unfavorable for clinical rescue, thereby limited Radix Rhodiolae further application clinically greatly.On the other hand, existing research to Radix Rhodiolae class medical material effective ingredient, all rhodioloside, butyl alcohol etc. as the treatment effective ingredient of cardiovascular and cerebrovascular disease and primary study, and ignored the pharmacological action of Radix Rhodiolae polysaccharide class, in preparation technology, often Radix Rhodiolae polysaccharide class material is removed as impurity.The pharmacologically active that studies show that the Radix Rhodiolae polysaccharide class according to modern pharmacy is very strong in fact, is very strong at the pharmacologically active aspect enhancing and the adjusting immunity of organism especially; Radix Rhodiolae polysaccharide also has certain blood sugar lowering, the effect of blood fat reducing, experimental results show that single Radix Rhodiolae decocting liquid just can effectively reduce post-prandial glycemia and blood fat; In addition, there are some researches show that also Radix Rhodiolae polysaccharide passes through certain machining function in cell membrane, stop the particulate absorption of Coxsackie virus and reach antiviral effect.
Summary of the invention
First purpose of the present invention provides a kind of Radix Rhodiolae effective component extracts; Second purpose of the present invention provides a kind of preparation method of Radix Rhodiolae effective component extracts; It is ejection preparation of primary raw material and preparation method thereof that the 3rd purpose of the present invention provides a kind of effective component extracts with Radix Rhodiolae.
Radix Rhodiolae effective component extracts provided by the invention obtains by following technological means.Process program 1:
After A, Radix Rhodiolae are ground into coarse powder, be that solution water decocts 3 extractions with water, each 1～3 hour, decocting liquid filtered the back and merges, and is the concentrated solution of 1.20～1.30 (20 ℃) with reclaim under reduced pressure jar simmer down to relative density.Add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%～85%, left standstill 36～48 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75%～85% washing with alcohol, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, getting relative density is 20 ℃ of concentrated solutions of 1.10～1.25 down;
B, add the ethanol mixing again, adjust to that to contain the alcohol amount be 75%～95%, left standstill 24～36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75%～95% washing with alcohol, filtration, and the filter cake reservation is standby, merging filtrate; Adjust pH value to 8.0 with 20%～30% sodium hydroxide solution, left standstill 24～48 hours, filter, remove impurity such as tannin at 4 ℃～8 ℃, decompression recycling ethanol, 20 ℃ of following relative densities are 1.10～1.25 concentrated extracting solution;
C, concentrated extracting solution are crossed the macropore resin bed and are analysed post, at first use 5～40 times water elution, and it is standby that eluent concentrates reservation; With 5～40 times 40%～85% ethanol elution, collect eluent again, decompression recycling ethanol, obtaining relative density is the concentrated extracting solution a of 1.10～1.25 (20 ℃);
Filter cake filters after with 5～10 times of water dissolutioies among D, steps A, the B, adds 2～4% active carbons and boils 15～30min, cold filtration; Cross the macropore resin bed after filtrate concentrates in addition and analyse post, with 5～40 times of water elutions, the merging of water elution concentrated solution obtains concentrated extracting solution b among concentrated back of eluent and the step C;
E, merging concentrated extracting solution a, b promptly get Radix Rhodiolae effective component extracts concentrated solution.
Process program 2:
A, Radix Rhodiolae pulverizing medicinal materials become coarse powder, doubly measure the alcohol reflux 2～4 times of 10-95% with 6-15 at every turn, and each 2～4 hours, merge extractive liquid, filtered, and medicinal residues keep standby; Decompression filtrate recycling ethanol and to be concentrated into 20 ℃ of following relative densities be 1.20～1.30 concentrated solution;
Add the water that 2-5 doubly measures in B, the concentrated solution, stir, cold preservation 12-72 hour, filter, it is 1.15～1.18 that filtrate decompression is concentrated into relative density, adding ethanol makes the alcohol amount of containing reach 80-85%, stir evenly, the sodium hydroxide solution of adding 20%～30% is adjusted about pH value to 8.0, leaves standstill 12～48 hours at 4 ℃～8 ℃, filter the concentrated extracting solution of decompression filtrate recycling ethanol and 20 ℃ of following relative densities 1.20～1.30 of simmer down to;
C, medicinal residues add 4～8 times of pure water and decoct each 1～3 hour 3 times; Merge 3 decocting liquids and filter, concentrating under reduced pressure is the concentrated extracting solution of 20 ℃ of following relative densities 1.20～1.30;
D, the concentrated solution among the B is crossed the macropore resin bed analyse post, at first use 5～40 times water elution, water elution liquid concentrates standby; With 5～40 times 40%～85% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.10～1.25 concentrated solution a;
E, concentrated solution among the step C is crossed the macropore resin bed analyse post, with 5～40 times water elution, eluent concentrates the back and merges with water elution concentrated solution among the step D and obtain concentrated solution b;
F, concentrated solution a, b merge, and promptly get Radix Rhodiolae effective component extracts concentrated solution.
The extract a that is mentioned in the above-mentioned preparation method mainly is Flavonoid substances such as rhodioloside and caffeic acid, butyl alcohol, gallic acid, and extract b mainly is a Radix Rhodiolae polysaccharide.
The above-mentioned Radix Rhodiolae effective component extracts concentrated solution that obtains can be made into the clinical any dosage form that is subjected to, as various dosage forms such as tablet, capsule, pill, granule, suspensoid, drop pill, oral liquid, injections.
A kind of Radix Rhodiolae ejection preparation provided by the invention is that the extract with the Tibetan medicine Radix Rhodiolae is the ejection preparation of primary raw material, contain rhodioloside 1～15%, butyl alcohol 0.1-5%, total flavones 10～35%, any one or a few effective ingredient mixture among the polysaccharide 25-45% etc.Be the Radix Rhodiolae effective component extracts concentrated solution that obtains above-mentioned, adjust pH value to 6.5～7.5, leave standstill, filter; Then through micro-pore-film filtration or ultrafiltration, the aseptic cillin bottle of packing into after filtrate concentrates, lyophilization, the tamponade sealing is made.
The quality standard of Radix Rhodiolae injection: the active component of Radix Rhodiolae injection detects based on rhodioloside and total flavones.Rhodioloside detects with high-efficient liquid phase technique, and total flavones detects with spectrophotography, and content calculates as standard with rutin.
What existing Radix Rhodiolae injection extraction process adopted is common water extraction, alcohol extracting method or the two lifting manipulations of water alcohol, and the extract that obtains at the two lifting manipulations of common pure water, water extraction, alcohol extracting method or be exactly the crude extract that contains impurity such as a large amount of tannins, starch, phytoprotein, it is exactly a part that has abandoned in the medical material effective ingredient, such as extract a or extract b, will inevitably lose the effective ingredient that a part has pharmacological action like this; And the present invention adopts the macroporous resin chromatographic column that the extract a or the extract b of rough segmentation made with extra care, and finally obtains purer extract.
The present invention can be used for treating cardiovascular and cerebrovascular disease, enhancing immunity, blood sugar lowering clinically.Because angina pectoris fall ill usually urgency, serious symptom, and effect of the present invention is direct, and is rapid-action, can be at short notice effective controlling symptoms, be beneficial to clinical rescue, thereby greatly promoted Radix Rhodiolae further application clinically.
Following experimental example is used to further specify the present invention.
Experimental example 1 decoction and alcohol sedimentation technique Study on extraction process:
(1), adopt orthogonal test to investigate different amount of water respectively, different decocting times, the receipts cream rate of Radix Rhodiolae extractum under the different conditions such as decoction number of times obtains best water and puies forward condition for adding 8 times of water gagings, decocts 3 times, decocting time is 3 hours at every turn.
(2), the condition of ethanol precipitation investigates and adopted orthogonal test equally, investigated the influence that sedimentary material is formed and the precipitation number of times is formed precipitate of Different concentrations of alcohol respectively.The practical situation of combined process production is taken all factors into consideration, and obtains best precipitate with ethanol condition and be 80% ethanol precipitation 2 times, precipitates 36～48 hours at every turn at low temperatures and is advisable.The precipitate that leaches under this condition mainly is materials such as starch, tannin, phytoprotein and Radix Rhodiolae polysaccharide.
(3), the filtrate behind the precipitate with ethanol is removed most of tannin precipitation with alkaline alcoholic liquor, residual tannin can eliminate when the macropore resin bed is analysed post substantially crossing in the filtrate.Filtrate is crossed the macropore resin bed and is analysed post, and wherein composition can be adsorbed by macroporous resin, just can reach the purpose of separation and purification respectively with different solvent elutions.Technological design elder generation water eluting obtains the polysaccharide eluent that do not have to be got off by ethanol precipitation fully, comes eluting to obtain being dissolved in alcoholic acid rhodioloside and total flavonoid with ethanol then.
(4), mainly contain polysaccharide and some tannins, phytoprotein or the like in the filter cake that gets off of ethanol precipitation, after being dissolved in water, with active carbon will be bigger the impurity absorption elimination, filtrate is crossed macroporous resin water eluting, can obtain purer Radix Rhodiolae polysaccharide.
(5), will separate rhodioloside, total flavones, the polysaccharide obtain of purifying respectively and merge, adjust pH value, filter with microporous membrane or ultrafiltration post, the bottling lyophilizing is promptly.
Experimental example 2 ethanol refluxing processes+water extraction Study on extraction process
(1), investigates the condition element such as consumption, time, number of times of alcohol reflux respectively with the method for orthogonal test, according to the height of the receipts cream rate under the different condition, obtaining best counterflow condition is: alcohol reflux 3 times, the alcohol reflux 3 hours that adds for the first time 10 times of amounts 75% adds the alcohol reflux 2 hours of 8 times of amounts 80% for the 2nd, 3 time.The backflow that obtains with this understanding is based on glycoside and total flavonoid basically, contains a spot of polysaccharide.Backflow can precipitate impurity such as removing most of tannin through water precipitating and alkaline alcoholic liquor.
(2), the polysaccharide composition in the medicinal residues that stay of reflux, extract, is residual more, because the dissolubility of polysaccharide in the ethanol of higher concentration is not high.Result according to investigating in the process program 1 adds 8 times of decoctings with medicinal residues and boils 3 times, each 2 hours.Obtain decocting liquid.Wherein based on polysaccharide, phytoprotein, starch, tannin etc.
(3), alcohol reflux liquid is concentrated the back cross the macropore resin bed and analyse post, first water eluting is failed complete sedimentary polysaccharose substance, it is standby to keep the water elution liquid that contains polysaccharide.Reuse ethanol is with glycoside and total flavonoid eluting.
(4), the decocting liquid of medicinal residues and filter cake merge the back and go to cross the macropore resin bed behind the bigger impurity with activated carbon adsorption and analyse post, collects water elution liquid and merge, do and just obtaining purer Radix Rhodiolae polysaccharide through concentrating spray.Experimental example 3 injection of the present invention are to the influence of the impatient infarction size of rat ischemia
Get body weight 20 of the rats of 220～260g, male and female half and half are divided into 2 groups at random.Matched group is the normal saline group.Each is organized rat and all carries out intraperitoneal anesthesia with pentobarbital sodium 40mg/kg (body weight).Dorsal position is fixed, and extremity insert needle electrode.Open the thoracic cavity and expose heart, close the thoracic cavity after the ligation anterior descending coronary.Behind the ligation arteria coronaria, each group femoral vein administration from peeling off in advance immediately.Before tracing ligation, after the ligation, the II lead electrocardiogram after the administration.Write down 1min after the ligation respectively, 15min, the ST section of 30min changes, and postoperative 6h opens breast clip heart, and freezing 2h removes left atrium, the weighing ventricular weight.Again with cardiac muscle from basad parallel 0.1cm slab that is cut into of the apex of the heart, put into 0.5% N-BT (being dissolved in PH by nitro blue tetrazolium liquid is the fresh reserve liquid that 7.4 phosphate buffer is made into), 37 ℃ of water bath with thermostatic control dyeing 15min, normal myocardium is dark blue color, infarcted myocardium is not painted, calculates infarcted region and accounts for the long-pending percentage ratio of visceral surface whole-heartedly.The results are shown in Table 1, the result shows: injection of the present invention has the obvious effect that improves rat heart muscle ischemia and myocardial infarct size.
Table 1 injection of the present invention is to the influence of the impatient infarction size of rat ischemia (x ± s)
| Group | Example number (n) | ST section (mV) | Myocardial infarction area (%) | ||
| 1min | 15min | 30min | |||
| The normal saline group | 10 | 0.56±0.13 | 0.61±0.15 | 0.69±0.08 | 38.46±4.8 |
| Injection group of the present invention | 10 | 0.51±0.12 | 0.56±0.15 | 0.59±0.07 | 31.24±3.5** |
Annotate: compare * * p＜0.01 with normal saline
Experimental example 4 injection of the present invention suppress thrombotest:
Get 50 of the SD kind rat of body weight about 300g, be divided into 5 groups at random, male and female half and half.Blank is a normal saline, and positive control is a heparin sodium, and test group is an injection of the present invention.Each is organized rat and all peels off 30min after the vena femoralis injection administration of left side, anaesthetize with urethane, it is long to peel off left common carotid artery 15mm, with the stimulating electrode of analyzer and temperature probe hook in arteries, with 1.5mA galvanic stimulation 5min, when intra-arterial during because of the thrombosis plug flow, the blood vessel far-end, temperature reduces, and begins to be called duration of congestion (OT) to temperature bust required time from stimulation, judges pharmacodynamics index with OT length.
The influence that table 2 ejection preparation of the present invention forms rat suppository (x ± S)
| Group | Dosage (g/kg) | Number of animals (only) | Duration of congestion (branch) |
| Contrast | 10 | 6.56±0.52 | |
| Heparin sodium | 100μ/kg iv | 10 | 9.56±2.98*** |
| Ejection preparation of the present invention | 20mg/kg iv | 10 | 7.34±1.7 |
* compare P＜0.05 with matched group
* compares P＜0.01 with matched group
* * compares P＜0.001 with matched group
The result shows: ejection preparation of the present invention has the thrombotic effect of inhibition.
Experimental example 5 injection of the present invention are to hemorheological influence:
Get 50 of SD kind rats about body weight 300g, be divided into 5 groups at random, male and female half and half.Blank group and hyperlipidemia (syndrome of blood stasis) model control group all gives normal saline, and test group is the Radix Rhodiolae injection of large, medium and small dosage.Method is: blank and hyperlipidemia group give the normal saline intravenous injection, and test group gives the ejection preparation intravenous injection of the present invention of various dose, every day 1 time, continuous 7 days; The rat of hyperlipidemia group and test group is all in test subcutaneous injection adrenalin hydrochloride injection 0.08ml/100g (body weight) on the 7th, the 4h duplicate injection of every interval once, the 1st injection back 2h immerses 5min in the frozen water, the equal fasting of each treated animal then with the modeling animal.Tested the 8th day, all experimental animals with the heparin sodium anticoagulant, are got anticoagulation all from the carotid artery blood-letting, put into centrifuge with the centrifugal 10min of the speed of 2000r/min after separated plasma to be measured.
Observation index:
Whole blood viscosity and plasma viscosity: with blood viscosity instrument at 37 ℃ of whole blood viscosity and plasma viscosities of measuring respectively under the different shear rates.(whole blood viscosity is represented hemorheological overall variation, and plasma viscosity has reflected the rheological behavior of soluble component in the blood, and is big more as viscosity, and blood flow is slow more, shows that then " blood stasis " symptom is heavy more)
Hematocrit: promptly measure in the blood perhaps hematocrit (HCT) of erythrocytic ratio.Get anticoagulated whole blood, detect with capillary blood specific volume of cell instrument.(HCT increases, and shows that whole blood concentration uprises, and it is big that viscosity becomes)
Erythrocyte sedimentation rate (ESR): get anticoagulated whole blood, detect, the reflection erythrocyte aggregation with Wintrobe pipe method.
Erythrocyte electrophoretic time: get anticoagulated whole blood, measure, reflect erythrocytic aggregation, slow down, illustrate that then the blood aggregation strengthens as erythrocytic electrophoresis time with the cell electrophoresis instrument.
Table 3 ejection preparation of the present invention is to hemorheological influence (x ± S)
| Group | Dosage (g/kg * d) | Whole blood viscosity (mPa*s) | Plasma viscosity (mPa*s) | Hematocrit (%) | Erythrocyte sedimentation rate (mm/h) | Erythrocyte electrophoretic time (s) | ||
| 3s -1 | 48s -1 | 200s -1 | ||||||
| Dosage group small dose group in the heavy dose of group of blank blood stasis model contrast | 20mg/kg×7 iv 10mg/kg×7 iv 5mg/kg×7iv | 18.85± 1.92 23.77± 1.85 18.26± 1.23** 19.82± 1.51** 20.39± 1.14* | 6.58± 0.86 8.49± 0.89 6.49± 1.24** 7.03± 0.79** 8.12± 0.86* | 4.80± 0.45 6.10± 0.46 4.83± 0.47** 5.12± 0.42** 5.68± 0.45* | 2.85± 0.31 3.68± 0.29 2.97± 0.25** 3.28± 0.25** 3.43± 0.27* | 41.50± 3.12 42.98± 4.39 41.75± 3.36** 42.46± 3.52** 42.83± 3.17* | 9.50± 3.96 10.38± 3.93 7.82± 3.26** 8.58± 3.71** 9.45± 3.73* | 16.63± 1.30 20.75± 1.98 16.27± 1.72** 18.62± 1.56** 19.97± 1.48* |
* compare P＜0.05 with the blood stasis model matched group
* compares P＜0.01 with the blood stasis model matched group
The result shows: the hemorheology index of the rat test group of use ejection preparation of the present invention is compared with blank and " blood stasis " card matched group and is improved significantly.
Experimental example 6 injection of the present invention are to the influence of anesthesiaing dog heart blood flowing dynamics and arteria coronaria flow
Get the domesticated dog about 20kg, with being fixed on the operating-table behind the pentobarbital injecting anesthetic.Tracheotomy connects artificial respirator; Separate femoral arteriography and measure arteriotony; Open breast exposure heart and place electromagnetic flowmeter probe measurement cardiac output and coronary flow respectively; Left ventricular cannulation is measured left ventricular pressure; Needle electrode is inserted the subcutaneous record of dog extremity II lead electrocardiogram measure heart rate; Trace the base portion of curve after the left indoor pressure signal of telecommunication amplifies and measure left chamber last diastolic pressure eventually; Left indoor pressure signal of telecommunication input electronic differentiator is measured the left indoor pressure rate of change.Above-mentioned every index synchronous recording is led physiograph in eight.
At first write down the normalized curve of the preceding These parameters of one section administration, then through intravenous injection injection of the present invention, the variation of every index after the record administration.(according to the data of direct measurement according to the following computing formula hemodynamic secondary parameters of can deriving: body surface area (m
2))=[body weight (kg)]
2/3* 0.11;
Table 4 injection of the present invention is to the influence of dog hemodynamics and arteria coronaria flow (x ± S)
| The measurement project | Before the administration | After the administration (15min) | After the administration (30min) | After the administration (60min) | After the administration (120min) |
| Heart rate is (inferior/min) systolic pressure (kPa) diastolic pressure (kPa) mean arterial pressure (kPa) left indoor pressure (kPa) left indoor pressure maximum climbing (kPa/s) cardiac output (L/min) stroke output (ml/ time) cardiac index (L/min.M2) SI (ml/ m 2) stroke work index (kg.M/min.M 2) total peripheral vascular resistance (kPa.s/L) coronary flow (ml/min) | 164± 8.6 18.3± 2.5 10.5± 2.4 13.7± 2.4 18.6± 2.9 339± 93.2 1.00± 0.1 5.95± 0.4 2.43± 0.2 15.70± 1.2 0.432± 0.15 1116.1± 327.1 116.2± 14.5 | 157.2± 9.4* 18.4± 1.2* 9.4± 2.5* 13.1± 3.2* 18.2± 2.4* 324.4± 91.2* 0.99± 0.2* 6.12± 0.2* 2.45± 0.3* 16.52± 2.3* 0.419± 0.14* 1107.2± 306.4* 126.1± 15.1** | 149.2± 8.4* 18.4± 2.1* 9.8± 2.1* 13.5± 3.5* 18.1± 2.8* 331.8± 89.5* 1.03± 0.2* 5.98± 0.1* 2.41± 0.8* 16.14± 1.4* 0.421± 0.21* 1106.8± 316.1* 128.7± 21.1** | 159.8± 5.1* 19.0± 1.4* 9.5± 1.9* 13.2± 3.1* 18.2± 2.1* 325.1± 85.2* 1.01± 0.3* 6.08± 0.4* 2.43± 0.2* 15.42± 1.5* 0.434± 0.14* 1114.2± 322.4* 128.1± 19.2** | 160.5± 8.5* 18.1± 1.7* 9.4± 2.3* 13.5± 1.9* 18.7± 1.1* 331.5± 88.1** 0.99± 0.2* 6.10± 0.2* 2.41± 0.2* 15.43± 1.8* 0.425± 0.28* 1112.8± 312.4* 127± 20.5** |
* with before the administration compare P＞0.05
Compare P＜0.01 before * and the administration
The result shows: all fluctuations to some extent of hemodynamic indexs such as heart rate, systolic pressure, diastolic pressure, mean arterial pressure, left indoor pressure and the maximum climbing speed of injection of the present invention injection back domesticated dog, cardiac output, total peripheral resistance, but with administration before comparing difference not remarkable; Coronary flow then has significant variation.Illustrate that Radix Rhodiolae can not increase myocardial contraction and left ventricular pressure, increase under the situation of cardiac work, effectively improve blood flow coronarius, thereby improve the blood supply situation of heart myocardial cell.
Experimental example 7 injection of the present invention are to the influence of experimental hyperglycemia
Get 30 of SD kind rats about body weight 300g, select 3～8 hours animals of serum glucose value more than 180mg/dl of fasting (can't help water), each animal average blood sugar value does not differ and should be divided into 3 groups, male and female half and half greater than 20mg/dl during grouping.Use the alloxan intravenously administrable, cause insulin to hang down the mo(u)ld bottom half hyperglycemia animal.The blank group gives normal saline, and positive controls gives insulin, and test group gives injection subcutaneous injection of the present invention.
The result shows: the hyperglycemic rat model blood glucose that insulin and injection of the present invention all can make alloxan cause descends, and shows that injection of the present invention has certain hypoglycemic activity.
Embodiment 1The preparation of Radix Rhodiolae effective component extracts
(1) get Radix Rhodiolae medical material 1000g and be ground into coarse powder after, add 8 times of decoctings and boil 3 extractions, each 3 hours, decocting liquid filtered the back and merges, and is the concentrated solution of 1.20～1.30 (20 ℃) with reclaim under reduced pressure jar simmer down to relative density.Add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%, left standstill 36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75% washing with alcohol, filtration, and the filter cake reservation is standby.Merging filtrate, with ethanol recycling can decompression recycling ethanol, getting relative density is the concentrated solution of 1.20 (20 ℃);
(2) add the ethanol mixing again in the above-mentioned concentrated solution, adjust to that to contain alcohol amount be 85%, left standstill 36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol, filtration, and the filter cake reservation is standby, merging filtrate.Sodium hydroxide solution with 25% is adjusted pH value to 8.0, leaves standstill 36 hours at 4 ℃～8 ℃, filter, and decompression recycling ethanol, getting relative density is the concentrated extracting solution of 1.20 (20 ℃).
(3) above-mentioned concentrated extracting solution is crossed the macropore resin bed and analyse post, at first use the water elution of 40 times of concentrated solution weight, eluent concentrates standby.With 80% ethanol elution of 40 times of concentrated solution weight, collect eluent again, decompression recycling ethanol, obtaining relative density is the concentrated extracting solution a of 1.20 (20 ℃).
(4) filter cake filters after with 10 times of water dissolutioies in the step (1) (2), adds 3% active carbon and boils 15～30min, cold filtration.Other crossed the macropore resin bed and analyses post after filtrate concentrated, and with 40 times of water elutions, eluent concentrates the back and the middle water elution concentrated solution merging of step (3) obtains concentrated extracting solution b.
(5) merge concentrated extracting solution a, b, promptly get Radix Rhodiolae effective component extracts concentrated solution 100m].
Embodiment 2The preparation of Radix Rhodiolae effective component extracts
(1), extract: Radix Rhodiolae medical material 1000g is ground into coarse powder, with the alcohol reflux of 10 times of amounts 85% 3 times, 2 hours first time, second and third time 1 hour.Merge extractive liquid, filters, and medicinal residues keep standby.Decompression filtrate recycling ethanol also is concentrated into the concentrated solution that relative density is 1.20 (20 ℃);
(2), the water that adds 5 times of amounts in the concentrated solution, stir, cold preservation 48 hours filters, and it is 1.18 that filtrate decompression is concentrated into relative density, adding ethanol again makes and contains alcohol amount and reach 85%, stir evenly, add sodium hydroxide solution and adjust about pH value to 8.0, left standstill 48 hours at 4 ℃～8 ℃, filter the concentrated extracting solution of decompression filtrate recycling ethanol and simmer down to relative density 1.20 (20 ℃);
(3), medicinal residues add 8 times of pure water decoctions 3 times, each 2 hours.Merge 3 decocting liquids and filter, concentrating under reduced pressure is the concentrated extracting solution of relative density 1.20 (20 ℃);
(4), the concentrated solution in (2) crossed the macropore resin bed analyse post, at first use 40 times water elution, water elution liquid concentrates standby.With 40 times 85% ethanol elution, collect ethanol elution again, decompression recycling ethanol, obtaining relative density is the concentrated solution a of 1.20 (20 ℃);
(5), in addition concentrated solution in the step (3) is crossed the macropore resin bed and analyses post, with 40 times water elution, eluent concentrates the back and obtains concentrated solution b with water elution concentrated solution merging in the step (4);
(6) concentrated solution a, b merge, and promptly get the concentrated solution 100ml of Radix Rhodiolae effective component extracts.
Embodiment 3The preparation of tablet of the present invention
Press the method for the foregoing description 1, get Radix Rhodiolae effective component extracts concentrated solution 100ml, make 1000 in tablet of the present invention according to a conventional method.
Embodiment 4The preparation of granule of the present invention
Press the method for the foregoing description 2, get Radix Rhodiolae effective component extracts concentrated solution 100ml, make 250 bags of granules of the present invention according to a conventional method, the 4g/ bag.
Embodiment 5The preparation of injection of the present invention
Press the method for the foregoing description 1, get Radix Rhodiolae effective component extracts concentrated solution 100ml, adjust pH value to 6.5～7.5, leave standstill, filter.Filtrate is through micro-pore-film filtration or through the ultrafiltration of ultrafiltration post.The filtrate aseptic cillin bottle of packing into, lyophilization, the tamponade sealing promptly gets 200 of lyophilized injectable powders of the present invention.
Embodiment 6The preparation of injection of the present invention
Press the method for the foregoing description 2, get Radix Rhodiolae effective component extracts concentrated solution 100ml, adjust pH value to 6.5～7.5, leave standstill, through micro-pore-film filtration or ultrafiltration, the aseptic cillin bottle of packing into after filtrate concentrates, lyophilization, the tamponade sealing promptly gets 200 of lyophilized injectable powders of the present invention.
Claims (13)
1, a kind of Radix Rhodiolae effective component extracts is characterized in that it being to be made by following method:
After A, Radix Rhodiolae are ground into coarse powder, be that aqueous solvent decocts 3 extractions with water, each 1～3 hour, decocting liquid filtered the back and merges, and was 1.20～1.30 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to; Add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%～85%, left standstill 36～48 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75%～85% washing with alcohol, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.10～1.25 concentrated solution;
B, add the ethanol mixing again, adjust to that to contain the alcohol amount be 75%～95%, left standstill 24～36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75%～95% washing with alcohol, filtration, and the filter cake reservation is standby, merging filtrate; Adjust pH value to 8.0 with 20%～30% sodium hydroxide solution, left standstill 24～48 hours, filter, remove tannin impurity at 4 ℃～8 ℃, decompression recycling ethanol, 20 ℃ of following relative densities are 1.10～1.25 concentrated extracting solution;
C, concentrated extracting solution are crossed the macropore resin bed and are analysed post, at first use 5～40 times water elution, and it is standby that eluent concentrates reservation; With 5～40 times 40%～85% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.10～1.25 concentrated extracting solution a;
Filter cake filters after with 5～10 times of water dissolutioies among D, steps A, the B, adds 2～4% active carbons and boils 15～30min, cold filtration; Cross the macropore resin bed after filtrate concentrates in addition and analyse post, with 5～40 times of water elutions, the merging of water elution concentrated solution obtains concentrated extracting solution b among concentrated back of eluent and the step C;
E, merging concentrated extracting solution a, b promptly get Radix Rhodiolae effective component extracts concentrated solution.
2, a kind of Radix Rhodiolae effective component extracts as claimed in claim 1 is characterized in that it being to be made by following method:
A. after Radix Rhodiolae is ground into coarse powder, be that aqueous solvent decocts 3 extractions with water, each 3 hours, decocting liquid filtered the back and merges, and was 1.20～1.30 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to; Add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%, left standstill 36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75% washing with alcohol, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, getting relative density is 20 ℃ of concentrated solutions of 1.20 down;
B, add the ethanol mixing again, adjust to that to contain the alcohol amount be 85%, left standstill 36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol, filtration, and the filter cake reservation is standby, merging filtrate; Adjust pH value to 8.0 with 25% sodium hydroxide solution, left standstill 36 hours, filter, remove tannin impurity at 4 ℃～8 ℃, decompression recycling ethanol, 20 ℃ of following relative densities are 1.20 concentrated extracting solution;
C, concentrated extracting solution are crossed the macropore resin bed and are analysed post, at first use 40 times water elution, and it is standby that eluent concentrates reservation; With 40 times 80% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.20 concentrated extracting solution a;
Filter cake filters after with 10 times of water dissolutioies among D, steps A, the B, adds 3% active carbon and boils 15～30min, cold filtration; Cross the macropore resin bed after filtrate concentrates in addition and analyse post, with 40 times of water elutions, the merging of water elution concentrated solution obtains concentrated extracting solution b among concentrated back of eluent and the step C;
E, merging concentrated extracting solution a, b promptly get Radix Rhodiolae effective component extracts concentrated solution.
3, a kind of Radix Rhodiolae effective component extracts is characterized in that it being to be prepared from by following method:
A, Radix Rhodiolae pulverizing medicinal materials become coarse powder, doubly measure the alcohol reflux 2～4 times of 10-95% with 6-15 at every turn, and each 2～4 hours, merge extractive liquid, filtered, and medicinal residues keep standby; Decompression filtrate recycling ethanol and to be concentrated into 20 ℃ of following relative densities be 1.20～1.30 concentrated solution;
Add the water that 2-5 doubly measures in B, the concentrated solution, stir, cold preservation 12-72 hour, filter, it is 1.15～1.18 that filtrate decompression is concentrated into relative density, adding ethanol makes the alcohol amount of containing reach 80-85%, stir evenly, the sodium hydroxide solution of adding 20%～30% is adjusted about pH value to 8.0, leaves standstill 12～48 hours at 4 ℃～8 ℃, filter the concentrated extracting solution of decompression filtrate recycling ethanol and 20 ℃ of following relative densities 1.20～1.30 of simmer down to;
C, medicinal residues add 4～8 times of pure water and decoct each 1～3 hour 3 times; Merge 3 decocting liquids and filter, concentrating under reduced pressure is the concentrated extracting solution of 20 ℃ of following relative densities 1.20～1.30;
D, the concentrated solution among the B is crossed the macropore resin bed analyse post, at first use 5～40 times water elution, water elution liquid concentrates standby; With 5～40 times 40%～85% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.10～1.25 concentrated solution a;
E, concentrated solution among the step C is crossed the macropore resin bed analyse post, with 5～40 times water elution, eluent concentrates the back and merges with water elution concentrated solution among the step D and obtain concentrated solution b;
F, concentrated solution a, b merge, and promptly get Radix Rhodiolae effective component extracts concentrated solution.
4, a kind of Radix Rhodiolae effective component extracts as claimed in claim 3 is characterized in that it being to be prepared from by following method:
A. the Radix Rhodiolae pulverizing medicinal materials becomes coarse powder, at every turn with 10 times of amount alcohol reflux of 85% 3 times, and 2 hours for the first time, second and third time 1 hour, merge extractive liquid, filters, and medicinal residues keep standby; Decompression filtrate recycling ethanol and to be concentrated into 20 ℃ of following relative densities be 1.20 concentrated solution;
B. the water that adds 5 times of amounts in the concentrated solution, stir, cold preservation 48 hours filters, and it is 1.18 that filtrate decompression is concentrated into relative density, adding ethanol makes and contains alcohol amount and reach 85%, stir evenly, add 20%～30% sodium hydroxide solution adjustment pH value to 8.0, left standstill 48 hours at 4 ℃～8 ℃, filter the concentrated extracting solution of decompression filtrate recycling ethanol and 20 ℃ of following relative densities 1.20 of simmer down to;
C, medicinal residues add 8 times of pure water and decoct each 2 hours 3 times; Merge 3 decocting liquids and filter, concentrating under reduced pressure is the concentrated extracting solution of 20 ℃ of following relative densities 1.20;
D, the concentrated solution among the B is crossed the macropore resin bed analyse post, at first use 40 times water elution, water elution liquid concentrates standby; With 40 times 85% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.20 concentrated solution a;
E, concentrated solution among the step C is crossed the macropore resin bed analyse post, with 40 times water elution, eluent concentrates the back and merges with water elution concentrated solution among the step D and obtain concentrated solution b;
F, concentrated solution a, b merge, and promptly get Radix Rhodiolae effective component extracts concentrated solution.
5, as claim 1,2,3,4 described a kind of Radix Rhodiolae effective component extracts, it is characterized in that making the dosage form of clinical acceptance.
6, a kind of Radix Rhodiolae effective component extracts as claimed in claim 5 is characterized in that described dosage form is tablet, capsule, pill, granule, suspensoid, drop pill, oral liquid or injection.
7, a kind of Radix Rhodiolae injection formulation is characterized in that the effective component extracts of Radix Rhodiolae in this injection formulation contains rhodioloside 1～15%, butyl alcohol 0.1～5%, total flavones 10～35%, polysaccharide 25～45%.
8, the preparation method of a kind of Radix Rhodiolae injection formulation as claimed in claim 7 is characterized in that this method is:
After A, Radix Rhodiolae are ground into coarse powder, be that aqueous solvent decocts 3 extractions with water, each 1～3 hour, decocting liquid filtered the back and merges, and was 1.20～1.30 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to; Add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%～85%, left standstill 36～48 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75%～85% washing with alcohol, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.10～1.25 concentrated solution;
B, add the ethanol mixing again, adjust to that to contain the alcohol amount be 75%～95%, left standstill 24～36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75%～95% washing with alcohol, filtration, and the filter cake reservation is standby, merging filtrate; Adjust pH value to 8.0 with 20%～30% sodium hydroxide solution, left standstill 24～48 hours, filter, remove tannin impurity at 4 ℃～8 ℃, decompression recycling ethanol, 20 ℃ of following relative densities are 1.10～1.25 concentrated extracting solution;
C, concentrated extracting solution are crossed the macropore resin bed and are analysed post, at first use 5～40 times water elution, and it is standby that eluent concentrates reservation; With 5～40 times 40%～85% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.10～1.25 concentrated extracting solution a;
Filter cake filters after with 5～10 times of water dissolutioies among D, steps A, the B, adds 2～4% active carbons and boils 15～30min, cold filtration; Cross the macropore resin bed after filtrate concentrates in addition and analyse post, with 5～40 times of water elutions, the merging of water elution concentrated solution obtains concentrated extracting solution b among concentrated back of eluent and the step C;
E, merging concentrated extracting solution a, b adjust pH value to 6.5～7.5, leave standstill, filter; Filtrate is through micro-pore-film filtration or through the ultrafiltration of ultrafiltration post; The filtrate aseptic cillin bottle of packing into, lyophilization, tamponade seals promptly.
9, the preparation method of a kind of Radix Rhodiolae injection formulation as claimed in claim 8 is characterized in that this method is:
A. after Radix Rhodiolae is ground into coarse powder, be that aqueous solvent decocts 3 extractions with water, each 3 hours, decocting liquid filtered the back and merges, and was 1.20～1.30 concentrated solution with relative density under the reclaim under reduced pressure jar simmer down to 20C; Add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%, left standstill 36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75% washing with alcohol, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, getting relative density is 20 ℃ of concentrated solutions of 1.20 down;
B, add the ethanol mixing again, adjust to that to contain the alcohol amount be 85%, left standstill 36 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol, filtration, and the filter cake reservation is standby, merging filtrate; Adjust pH value to 8.0 with 25% sodium hydroxide solution, left standstill 36 hours, filter, remove tannin impurity at 4 ℃～8 ℃, decompression recycling ethanol, 20 ℃ of following relative densities are 1.20 concentrated extracting solution;
C, concentrated extracting solution are crossed the macropore resin bed and are analysed post, at first use 40 times water elution, and it is standby that eluent concentrates reservation; With 40 times 80% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.20 concentrated extracting solution a;
Filter cake filters after with 10 times of water dissolutioies among D, steps A, the B, adds 3% active carbon and boils 15～30min, cold filtration; Cross the macropore resin bed after filtrate concentrates in addition and analyse post, with 40 times of water elutions, the merging of water elution concentrated solution obtains concentrated extracting solution b among concentrated back of eluent and the step C;
E, merging concentrated extracting solution a, b adjust pH value to 6.5～7.5, leave standstill, filter; Filtrate is through micro-pore-film filtration or through the ultrafiltration of ultrafiltration post; The filtrate aseptic cillin bottle of packing into, lyophilization, tamponade seals promptly.
10, the preparation method of a kind of Radix Rhodiolae injection formulation as claimed in claim 7 is characterized in that this method is:
A, Radix Rhodiolae pulverizing medicinal materials become coarse powder, doubly measure the alcohol reflux 2～4 times of 10-95% with 6-15 at every turn, and each 2～4 hours, merge extractive liquid, filtered, and medicinal residues keep standby; Decompression filtrate recycling ethanol and to be concentrated into 20 ℃ of following relative densities be 1.20～1.30 concentrated solution;
Add the water that 2-5 doubly measures in B, the concentrated solution, stir, cold preservation 12-72 hour, filter, it is 1.15～1.18 that filtrate decompression is concentrated into relative density, adding ethanol makes the alcohol amount of containing reach 80-85%, stir evenly, the sodium hydroxide solution of adding 20%～30% is adjusted about pH value to 8.0, leaves standstill 12～48 hours at 4 ℃～8 ℃, filter the concentrated extracting solution of decompression filtrate recycling ethanol and 20 ℃ of following relative densities 1.20～1.30 of simmer down to;
C, medicinal residues add 4～8 times of pure water and decoct each 1～3 hour 3 times; Merge 3 decocting liquids and filter, concentrating under reduced pressure is the concentrated extracting solution of 20 ℃ of following relative densities 1.20～1.30;
D, the concentrated solution among the B is crossed the macropore resin bed analyse post, at first use 5～40 times water elution, water elution liquid concentrates standby; With 5～40 times 40%～85% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.10～1.25 concentrated solution a;
E, concentrated solution among the step C is crossed the macropore resin bed analyse post, with 5～40 times water elution, eluent concentrates the back and merges with water elution concentrated solution among the step D and obtain concentrated solution b;
F, concentrated solution a, b merge, and adjust pH value to 6.5～7.5, leave standstill, filter; Then through micro-pore-film filtration or ultrafiltration, the aseptic cillin bottle of packing into after filtrate concentrates, lyophilization, the tamponade sealing, promptly.
11, the preparation method of a kind of Radix Rhodiolae injection formulation as claimed in claim 10 is characterized in that this method is:
A. the Radix Rhodiolae pulverizing medicinal materials becomes coarse powder, at every turn with 10 times of amount alcohol reflux of 85% 3 times, and 2 hours for the first time, second and third time 1 hour, merge extractive liquid, filters, and medicinal residues keep standby; Decompression filtrate recycling ethanol and to be concentrated into 20 ℃ of following relative densities be 1.20 concentrated solution;
B. the water that adds 5 times of amounts in the concentrated solution, stir, cold preservation 48 hours filters, and it is 1.18 that filtrate decompression is concentrated into relative density, adding ethanol makes and contains alcohol amount and reach 85%, stir evenly, add 20%～30% sodium hydroxide solution adjustment pH value to 8.0, left standstill 48 hours at 4 ℃～8 ℃, filter the concentrated extracting solution of decompression filtrate recycling ethanol and 20 ℃ of following relative densities 1.20 of simmer down to;
C, medicinal residues add 8 times of pure water and decoct each 2 hours 3 times; Merge 3 decocting liquids and filter, concentrating under reduced pressure is the concentrated extracting solution of 20 ℃ of following relative densities 1.20;
D, the concentrated solution among the B is crossed the macropore resin bed analyse post, at first use 40 times water elution, water elution liquid concentrates standby; With 40 times 85% ethanol elution, collect eluent again, decompression recycling ethanol obtains 20 ℃ of following relative densities and is 1.20 concentrated solution a;
E, concentrated solution among the step C is crossed the macropore resin bed analyse post, with 40 times water elution, eluent concentrates the back and merges with water elution concentrated solution among the step D and obtain concentrated solution b;
F, concentrated solution a, b merge, and adjust pH value to 6.5～7.5, leave standstill, filter; Then through micro-pore-film filtration or ultrafiltration, the aseptic cillin bottle of packing into after filtrate concentrates, lyophilization, the tamponade sealing, promptly.
12,, it is characterized in that containing among the concentrated solution a rhodioloside, caffeic acid, butyl alcohol, gallic acid as the preparation method of claim 8,9,10,11 described a kind of Radix Rhodiolae injection formulations.
13,, it is characterized in that containing Radix Rhodiolae polysaccharide among the concentrated solution b as the preparation method of claim 8,9,10,11 described a kind of Radix Rhodiolae injection formulations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410037408 CN1268319C (en) | 2004-04-30 | 2004-04-30 | Rhodiola sacra injection and its preparation |
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| CN 200410037408 CN1268319C (en) | 2004-04-30 | 2004-04-30 | Rhodiola sacra injection and its preparation |
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| CN1569196A CN1569196A (en) | 2005-01-26 |
| CN1268319C true CN1268319C (en) | 2006-08-09 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1969930B (en) * | 2005-11-04 | 2010-08-11 | 四川宇妥藏药药业有限责任公司 | Method for preparing rhodiola root extract transformed by microbe |
| CN101863871B (en) * | 2010-05-20 | 2012-01-18 | 于非 | Total glycosides of Rhodiola rosea, medical application and preparation method thereof |
| CN102692464A (en) * | 2012-06-15 | 2012-09-26 | 通化玉圣药业股份有限公司 | Rhodiola rosea injection fingerprint spectrum check method |
| CN104435057B (en) * | 2014-12-19 | 2018-01-23 | 通化玉圣药业有限公司 | Gadol injection low temperature carbon removal preparation method |
| CN112194689B (en) * | 2020-09-27 | 2022-08-30 | 湖南朗林生物资源股份有限公司 | Method for extracting effective active ingredients of rhodiola rosea |
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