CN1268323C - Rhodiola sacra soft capsule and its preparation - Google Patents
Rhodiola sacra soft capsule and its preparation Download PDFInfo
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- CN1268323C CN1268323C CN 200410037407 CN200410037407A CN1268323C CN 1268323 C CN1268323 C CN 1268323C CN 200410037407 CN200410037407 CN 200410037407 CN 200410037407 A CN200410037407 A CN 200410037407A CN 1268323 C CN1268323 C CN 1268323C
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Abstract
The present invention discloses an extract of effective parts of rhodiola sacra and a preparation method thereof, and the present invention also discloses a soft capsule preparation which uses an extract of effective parts of rhodiola sacra as principal raw materials and a preparation method thereof. The extract of the effective parts of rhodiola sacra contains salidroside, tyrosol, total flavonoids and polysaccharide, and the present invention is made by extracting the rhodiola sacra by a water extraction and precipitation method or an alcohol backwashing method with a water extraction method. The extract is added in solvents of which the temperature is 60 to 80 DEG C to dissolve, and then, stabilizing agents and suspending agents are added. After the mixture is uniformly stirred, suspensions are processed by a colloid mill, the suspensions are degassed and evacuated, pills are pressed, washed and dried, and the rhodiola sacra soft capsule is obtained. Compared with the existing preparation formulation, the soft capsule of the present invention has the advantages of greatly reduced dosage, higher bioavailability, more exact curative effect, good stability, direct action and quick effect.
Description
Technical field
The present invention relates to a kind of Chinese medicinal soft capsule preparation and preparation method thereof, particularly relate to a kind of Radix Rhodiolae soft capsule preparation and preparation method thereof, belong 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. (Rhodio1a 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.”
That uses clinically at present only has tablet, hard capsule, oral liquid, granule etc. with Radix Rhodiolae as the product forms of primary raw material, be the crude extract preparation of Radix Rhodiolae, contain excipient, disintegration time is longer, onset is slow, and the medication cycle is long, can't be at short notice effective controlling symptoms, can not satisfy clinically the needs of disease controlling in a short time, thereby limit Radix Rhodiolae further application clinically greatly.
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 soft capsule preparation of primary raw material and preparation method thereof that the 3rd purpose of the present invention provides a kind of effective part extract with Radix Rhodiolae.
Radix Rhodiolae extrtact provided by the invention is to be that raw material extracts with the Tibetan medicine Radix Rhodiolae about growth height above sea level 3500 meters～5000m, for containing 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%.Can obtain 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 was 1.20～1.30 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B, 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 1～3 time, 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;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 75%～85% ethanol elution, eluent concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
After D, filter cake were dissolved in water, the active carbon of adding 2%～4% filtered with 400 order filter clothes after boiling 15min～30min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
E, extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 1%～99%: 1%～99% mixed.
Process program 2,
A, Radix Rhodiolae are ground into coarse powder, and with 75%～85% alcohol reflux 1-3 time, each solvent amount is 5～10 times of Medicinal powder of Rhodiola rosea L., and each 1～4 hour extraction time, medicinal residues keep standby;
B, merge alcohol extract, filter with 400 order filter clothes, precipitation is with 75%～85% washing with alcohol 1～3 time, filtration, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.10～1.25 of simmer down to;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 10～40 times of distilled water eluting, eluent keeps standby; With 10～40 times 75%～85% ethanol elution, ethanol elution obtains extract A through concentrated, spray drying again;
D, medicinal residues decoct with water 2～3 times, each 1～3 hour, collecting decoction, filter, after boiling 15min～30min, the active carbon that adds filter cake among the B and 2%～4% filters with 400 order filter clothes, concentrated filtrate is crossed the macropore resin bed in addition and is analysed post, merges C, D water elution liquid with 10～40 times of distilled water eluting, and spray drying obtains extract B;
E, extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 1%～99%: 1%～99% mixed.
The extract a that mentions in the above-mentioned preparation method mainly is Flavonoid substances such as rhodioloside and caffeic acid, butyl alcohol, gallic acid; Extract b mainly is a Radix Rhodiolae polysaccharide.
Radix Rhodiolae soft capsule preparation provided by the invention is that the extract with the Tibetan medicine Radix Rhodiolae about growth height above sea level 3500 meters～5000m is the soft capsule 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%.Soft capsule preparation of the present invention is the Radix Rhodiolae effective component extracts to be added in 60～80 ℃ the solvent dissolve; Add adjuvants such as stabilizing agent, suspending agent, surfactant again, after stirring suspension crossed colloid mill, degassing evacuation, is washed ball, drying at pelleting, makes.
In Radix Rhodiolae soft capsule preparation of the present invention, Radix Rhodiolae effective ingredient effective extract accounts for soft capsule content 20%～50%; Adjuvant accounts for soft capsule content 40%～70%; Stabilizing agent, suspending agent account for 10%～30% of soft capsule content.
Described adjuvant wherein solvent can be any one or any several mixture in vegetable oil, PGE, isopropyl alcohol, glycerol, tween 80, water or the like, accounts for soft capsule content 40%～70%; Adjuvant such as stabilizing agent, suspending agent can be any one or a few the mixture in glycerol, water, soybean lecithin, Cera Flava, aluminum monostearate, ethyl cellulose, the solid polyethylene glycol etc., accounts for 10%～30% of soft capsule content.
Radix Rhodiolae soft capsule quality standard of the present invention: the active component of Radix Rhodiolae soft capsule 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.
Rhodioloside, butyl alcohol etc. have oxygen lack resistant function in the Radix Rhodiolae, can obviously prolong the mice hypobaric hypoxia following time-to-live of environmental condition; Have antifatigue effect, its can significant prolongation mice swimming with a load attached to the body time and makes and grab rod and drop the time significant prolongation, can also increase oxygen content in the blood in addition, eliminates in the blood, in the muscle lactic acid and piles up, and reaches the purpose of allaying tiredness.
Soft capsule of the present invention is that primary raw material is prepared from by the Radix Rhodiolae effective ingredient, is the extract preparation, and dose is little, and bioavailability height, effective ingredient are definite, good stability, effect are direct, rapid-action; Can be at short notice effective controlling symptoms, satisfy clinically the needs of disease controlling in a short time, can greatly promote Radix Rhodiolae further application clinically.
Following experimental example is used to further specify the present invention.
The research (decoction and alcohol sedimentation technique) of experimental example 1 Radix Rhodiolae extraction process of effective component:
(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, and each decocting time is 3 hours.
(2) condition of ethanol precipitation is investigated and have been adopted orthogonal test equally, has investigated the precipitation capacity of Different concentrations of alcohol such as 75%, 80%, 85% 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 48 hours.The precipitate that leaches mainly contains starch, tannin, phytoprotein and Radix Rhodiolae polysaccharide.
(3) concentrated solution is crossed the macropore resin bed and analysed post, composition can be adsorbed by macroporous resin in the concentrated solution, 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 be polysaccharide and some tannins, phytoprotein or the like in the filter cake that ethanol precipitation gets off, after being dissolved in water, with the impurity absorption elimination, merge the concentrated dried purer Radix Rhodiolae polysaccharide that just obtains that sprays with water elution liquid with active carbon.
The research (ethanol refluxing process+water extraction) of experimental example 2 Radix Rhodiolae extraction process of effective component:
(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.Adjust the alcohol amount that contains of reflux extracting liquid, material such as polysaccharide is precipitated as far as possible.
(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 and cross the macropore resin bed and analyse post, first water eluting is failed complete sedimentary polysaccharose substance, and 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, collect water elution liquid and merge, and do and just obtaining purer Radix Rhodiolae polysaccharide through concentrating spray.
The pharmacodynamic study of experimental example 3 soft capsules of the present invention
Radix Rhodiolae soft capsule clinical medicine dose is 1～2/time, and 3 times/day, soft capsule contains solid constituent 0.25g/ grain, and clinical maximum dosage is 3.0g/60kg (being equivalent to 0.05/kg).Animal dosage is respectively 1g/kg, 0.5g/kg, and 0.25g/kg is equivalent to 20 times of clinical dosage, and 10 times, 5 times.
One, medication: gastric infusion is consistent with the clinical administration approach, every day 1 time, and successive administration 7 days, 60min tests after the last administration.
Two, contrast:
1. blank: isopyknic normal saline;
2. positive control: " Nuodikang " capsule (Tibet Nuodikang Pharmaceutical Co., Ltd.), dosage are equivalent to 10 times of clinical dosages.
Three, statistical method: adopt T check or X
2Check.
Four, method and result:
(1) anti-fatigue test
1, the mice swimming with a load attached to the body time: 50 of mices are divided into 5 groups, male and female half and half at random.The 1st group is normal saline blank group, and the 2nd group is " Nuodikang " capsule matched group, and the 3rd, 4,5 groups is the large, medium and small dosage group of Radix Rhodiolae soft capsule.Successive administration 7 days after the last administration behind the 60min, with the mouse tail 2g that bears a heavy burden, places depth of water 40cm, and in the calorstat that water temperature is 25 ℃, the record mice is Zi emerging as swimming time on no longer in the weak sinking 40s that begins to swim.The result shows that Radix Rhodiolae soft capsule high dose group can obviously prolong the mice swimming time, improves motor capacity.
2, normal pressure hypoxia endurance time: 50 of mices are divided into 5 groups, male and female half and half at random.The 1st group is normal saline blank group, and the 2nd group is " Nuodikang " capsule matched group, and the 3rd, 4,5 groups is the large, medium and small dosage group of Radix Rhodiolae soft capsule.Successive administration 7 days behind the 60min, places mice in the exsiccator that fills soda lime after the last administration, and the record mice is from putting into the dead time, as the time of mice normal pressure anoxia enduring.The result shows that Radix Rhodiolae soft capsule high dose group can obviously prolong mice normal pressure hypoxia endurance time, improves the ability of mice anoxia enduring.
3, mice pole-jump test: 50 of mices are divided into 5 groups, male and female half and half at random.The 1st group is normal saline blank group, and the 2nd group is " Nuodikang " capsule matched group, and the 3rd, 4,5 groups is the large, medium and small dosage group of Radix Rhodiolae soft capsule.Successive administration 7 days behind the 60min, places long 100cm with mice after the last administration, diameter 0.7cm, and on the smooth glass rod of vertical hanging, the record mice is because of the unable time that is slipped to ground from the upper end of fatigue.The result shows that Radix Rhodiolae soft capsule high dose group can obviously improve the ability of mouse anti-reflecting fatigue.
Table 1 Radix Rhodiolae soft capsule of the present invention antifatigue effect (X ± SD)
| Group | Dosage g/kg * d | Swimming time min | Hypoxia endurance time min | Pole-climbing time min |
| Dosage group small dose group in the heavy dose of group of blank positive control | 0.56g/kg×7 1g/kg×7 0.5g/kg×7 0.25g/kg×7 | 4.12±0.73 4.67±1.04* 5.96±1.47 4.73±0.89* 4.09±0.86 | 17.86±3.63 22.03±3.92** 24.78±3.64** 22.43±3.21** 19.48±4.29** | 12.60±0.03 16.39±8.92* 17.56±11.32 15.94±9.06* 13.77±10.65 |
Compare with matched group: * P＜0.05 * * P＜0.01
(2) enhance immunity test
1, to mouse immune organ weight's influence: get 50 of body weight 10～15g children Mus, be divided into 5 groups at random, male and female half and half.The 1st group is normal saline blank group, and the 2nd group is " Nuodikang " capsule matched group, and the 3rd, 4,5 groups is the large, medium and small dosage group of Radix Rhodiolae soft capsule.Successive administration 7 days was weighed after the last administration in 24 hours, extractd the eyeball sacrificed by exsanguination, and extraction thymus and spleen are weighed, and calculated thymus or index and spleen index with following formula.
Thymus and spleen are important immune organs in the body.Thymus is as primary lymphatic organ, and the hematopoietic stem cell of migration enters primordium of thymus, becomes the T lymphocyte at this differentiation and proliferation, and is relevant with cellular immunization.Spleen is a secondary lymphatic organ, immunologically competent cell can be divided a word with a hyphen at the end of a line in this, and be subjected to antigenic stimulus in the immunologic process herein and further proliferation and differentiation and maturation, and T lymphocyte, bone-marrow-derived lymphocyte and macrophage etc. are arranged in the spleen, with humoral immunization and cellular immunization relation is arranged all.The Radix Rhodiolae polysaccharide that contains in the Radix Rhodiolae is a kind of immunomodulator, and thymus of mice or spleen weight are increased.Result of the test shows: the test group mouse thymus exponential sum spleen index of taking the Radix Rhodiolae soft capsule has tangible rising.
Table 2 the present invention is to mouse immune organ weight's influence (X ± SD)
| Group | Dosage g/kg * d | Body weight (g) | Thymus index | Index and spleen index |
| Dosage group small dose group in the heavy dose of group of blank positive control | 0.56g/kg×7 1g/kg×7 0.5g/kg×7 0.25g/kg×7 | 13.5±1.3 13.8±1.2 13.5±0.9 13.7±1.2 13.3±1.6 | 4.26±0.39 5.02±0.47** 5.96±0.37** 5.04±0.72** 4.97±0.38* | 5.38±0.57 6.21±0.78** 6.93±0.57** 6.30±0.12** 5.93±0.54* |
Compare with the blank group: * P＜0.05 * * P＜0.01
1, to the influence of mice reticuloendothelial system phagocytic activity:
50 of mices are divided into 5 groups, male and female half and half at random.The 1st group is normal saline blank group, and the 2nd group is " Nuodikang " capsule matched group, and the 3rd, 4,5 groups is the large, medium and small dosage group of Radix Rhodiolae soft capsule.Successive administration 7 days behind the 60min, injects 20% prepared Chinese ink 0.1ML/10g by the tail vein after the last administration, and injection back 2min and 15min get blood 20 μ l respectively by left and right sides eye socket, are dissolved in 0.1%Na
2CO
3Shake up in the solution, place 7510 spectrophotometers to survey its absorbance (D) in the 600nm place, according to K=(LogD
1-LogD
2)/13 are calculated and are cleaned up index.The result shows: the clearance rate of the heavy dose of test group of Radix Rhodiolae soft capsule is significantly increased.
2, to the influence of mice serum hemolysin level:
50 of mices are divided into 5 groups, male and female half and half at random.The 1st group is normal saline blank group, and the 2nd group is " Nuodikang " capsule matched group, and the 3rd, 4,5 groups is the large, medium and small dosage group of Radix Rhodiolae soft capsule.Successive administration 7 days.Tested the 1st day, the equal lumbar injection 5% chicken red blood cell 0.2ml/ of test mice only stimulates mice to produce immunoreation, tests the 8th day, wins eyeball of mouse and gets blood, puts into the centrifugal 10min of centrifuge 3000r/min, and gained serum dilutes 100 times with normal saline.Get the serum 1ml of dilution, add 5% chicken red blood cell 0.5ml, 10% complement 0.5ml puts into 37 ℃ calorstat water-bath 30min, 0 ℃ of cessation reaction behind the mixing.With the centrifugal 10min of aforesaid liquid 3000r/min, get supernatant in 721 spectrophotometer 540nm place colorimetrics, survey OD value (is accent " O " benchmark with increase serum not).The result shows: hemolysin is significantly increased in the mice serum of the heavy dose of test group of Radix Rhodiolae soft capsule.
Table 3 the present invention is to the influence of mice carbon clearance and serum hemolysin (X ± SD)
| Group | Dosage (g/kg * d) | Clean up index (X ± SD) | Hemolysin (OD value) (X ± SD) |
| Dosage group small dose group in the heavy dose of group of blank positive control | 0.56g/kg×7 1g/kg×7 0.5g/kg×7 0.25g/kg×7 | 0.0534±0.031 0.082±0.25* 0.094±0.069* 0.085±0.062* 0.059±0.015 | 0.100±0.069 0.307±0.099* 0.372±0.084* 0.292±0.113* 0.223±0.126 |
Compare with matched group: * P＜0.05 * * P＜0.01
(3) suppress thrombotest
Improve a little by the Htadove method, 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 the Radix Rhodiolae soft capsule of large, medium and small dosage.Each organizes rat 1h behind gastric infusion, 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 4 the present invention forms rat suppository (X ± S)
| Group | Dosage (g/kg) | Number of animals (only) | Duration of congestion (branch) |
| Contrast heparin sodium Radix Rhodiolae soft capsule Radix Rhodiolae soft capsule Radix Rhodiolae soft capsule | 100μ/kgiv 0.5 1.0 2.0 | 10 10 10 10 10 | 6.56±0.52 9.23±3.34*** 7.21±1.4 7.79±1.53* 7.96±1.27** |
* compare P＜0.05 with matched group
* compares P＜0.01 with matched group
* * compares P＜0.001 with matched group
The result shows: the Radix Rhodiolae soft capsule of doses has the thrombotic effect of inhibition.
(4) 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 soft capsule of large, medium and small dosage.Method is: blank and hyperlipidemia group give normal saline, and test group gives the Radix Rhodiolae soft capsule gastric infusion 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:
1, 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 " is heavy more)
2, 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)
3, erythrocyte sedimentation rate (ESR): get anticoagulated whole blood, detect, the reflection erythrocyte aggregation with Wintrobe pipe method.
4, 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 5 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 | 2.0/kg×7 1.0g/kg×7 0.5g/kg×7 | 18.85±1.92 23.77±1.85 19.25±1.79** 21.37±1.27* 21.87±1.04* | 6.58±0.86 8.49±0.89 7.39±0.76** 7.95±0.87* 8.19±0.82* | 4.80±0.45 6.10±0.46 5.14±0.42** 5.68±0.51** 5.82±0.42* | 2.85±0.31 3.68±0.29 3.16±0.33** 3.38±0.25* 3.59±0.37* | 41.50±3.12 42.98±±4.39 41.95±3.78** 42.16±4.82* 42.79±5.17* | 9.50±3.96 10.38±3.93 7.84±3.82** 8.45±3.34** 9.15±3.73* | 16.63±1.30 20.75±1.98 16.35±1.94** 18.83±1.79* 19.59±1.85* |
* compare P＜0.05 with matched group
* compares P＜0.01 with matched group
The result shows: the hemorheology of taking the rat test group of Radix Rhodiolae soft capsule is learned index and is compared with blank and " blood stasis " card matched group and improve significantly.
The internal metabolism kinetics comparative test of experimental example 4 soft capsules of the present invention and hard capsule
Get 10 of SD kind adult rats about body weight 300g, divide 2 groups at random, each 1 group of Radix Rhodiolae soft capsule and hard capsule (Nuodikang capsule) test group compares test and investigates soft capsule dosage form and the disintegrate in vivo of hard capsule dosage form, absorption process.Each organizes rat respectively with 10 times of disposable gastric infusions of clinical using dosage (stomach is all irritated with the aqueous solution or the oil solution of content in soft capsule 0.25g/ grain * 12, capsule 0.28g/ grain * 12).After the administration, serve as to detect index, be determined at the blood drug level of rhodioloside in the different time points rat blood with the HPLC method with rhodioloside in the preparation.Area under blood drug level-time graph (AUC0-t) calculates with trapezoidal method, blood peak concentration of drug (C
Max) and peak time (T
Max) directly obtain by test data, adopt two-one sided test, the AUC of soft capsule dosage form and capsule formulation is carried out evaluation of bioequivalence, eliminate half-life (T
1/2) adopt the 3P87 medicine to calculate for process simulation.
The result shows: soft capsule preparation of the present invention is given after the rat oral gavage administration, and rhodioloside reaches the time and the capsule reduced in comparison of peak concentration in its blood plasma, and its blood peak concentration of drug also raises to some extent.Difference between the two has significance.Pointing out soft capsule preparation of the present invention is not only to change to some extent on dosage form, because the change of extraction process, the refining of effective ingredient makes it be more prone to be absorbed by body, onset faster.
Embodiment 1The extraction of Radix Rhodiolae effective ingredient (decoction and alcohol sedimentation technique)
(1) get Radix Rhodiolae 1000g and be ground into coarse powder after, be that solution water decocts 3 times and extracts with water, add the water of 8 times of amounts at every turn, decocting time is 3 hours, decocting liquid filters the back and merges, and is the concentrated solution of 1.20 (20 ℃) with reclaim under reduced pressure jar simmer down to relative density.
(2) add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 80%, left standstill 48 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol 1～3 time, 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 ℃);
(3) get in (2) concentrated solution and cross the macropore resin bed and analyse post, earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 80% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again.
(4) filter cake that keeps in (2) is dissolved in water after, add 4% active carbon and boil 15min, filter with 400 order filter clothes, filtrate in addition the macropore resin bed analyse post, with 10～40 times of water elutions.Merge, concentrate the water elution liquid in (3) (4), the spray-dried extract b that obtains.
A, b are become the extract of Radix Rhodiolae effective ingredient by 20%: 80% mixed.
Embodiment 2The extraction of Radix Rhodiolae effective ingredient (decoction and alcohol sedimentation technique)
A, get Radix Rhodiolae 2000g and be ground into coarse powder after, be that solution water decocts 3 times and extracts with water, each 2 hours, decocting liquid filtered the back and merges, and was 1.25 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B, add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%, left standstill 48 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 80% washing with alcohol 1～3 time, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.25 concentrated solution;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 75% ethanol elution, ethanol elution concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
After D, filter cake were dissolved in water, the active carbon of adding 2% filtered with 400 order filter clothes after boiling 15min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
Extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 30%: 70% mixed.
Embodiment 3The extraction of Radix Rhodiolae effective ingredient (decoction and alcohol sedimentation technique)
A, get Radix Rhodiolae 1500g and be ground into coarse powder after, be that solution water decocts 3 times and extracts with water, each 3 hours, decocting liquid filtered the back and merges, and was 1.30 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B, add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 80%, left standstill 40 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75% washing with alcohol 1～3 time, 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 concentrated solution;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 80% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
After D, filter cake were dissolved in water, the active carbon of adding 3% filtered with 400 order filter clothes after boiling 20min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
Extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 40%: 60% mixed.
Embodiment 4The extraction of Radix Rhodiolae effective ingredient (decoction and alcohol sedimentation technique)
A, get Radix Rhodiolae 3000g and be ground into coarse powder after, be that solution water decocts 3 times and extracts with water, each 1 hour, decocting liquid filtered the back and merges, and was 1.20 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B, add the ethanol mixing in this concentrated solution, 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 80% washing with alcohol 1～3 time, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.20 concentrated solution;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 85% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
After D, filter cake were dissolved in water, the active carbon of adding 4% filtered with 400 order filter clothes after boiling 30min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
Extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 50%: 50% mixed.
Embodiment 5The extraction of Radix Rhodiolae effective ingredient (decoction and alcohol sedimentation technique)
A, get Radix Rhodiolae 2500g and be ground into coarse powder after, be that solution water decocts 3 times and extracts with water, each 2 hours, decocting liquid filtered the back and merges, and was 1.25 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B, add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%, left standstill 42 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol 1～3 time, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.25 concentrated solution;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 75% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
After D, filter cake were dissolved in water, the active carbon of adding 3% filtered with 400 order filter clothes after boiling 20min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
Extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 10%: 90% mixed.
Embodiment 6The extraction of Radix Rhodiolae effective ingredient (ethanol refluxing process+water extraction)
(1) gets Radix Rhodiolae 1000g and be ground into coarse powder,, add the alcohol reflux 3 hours of 10 times of amounts 75% for the first time, add the alcohol reflux 2 hours of 8 times of amounts 80% for the 2nd, 3 time with alcohol reflux 3 times.Medicinal residues keep standby.
(2) merge alcohol extract, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol 3 times, filtration, and the filter cake reservation is standby.Decompression recycling ethanol, the concentrated solution of simmer down to relative density 1.10 (20 ℃).
(3) concentrated solution in (2) is crossed the macropore resin bed and analyse post, earlier with 40 times of distilled water eluting, eluent keeps standby.With 40 times 75% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again.
(4) the slag decocting that adds 8 times of amounts boils 3 times, and each 2 hours, collecting decoction filtered, and filters with 400 order filter clothes after the active carbon that adds filter cake in (2) and 4% boils 20min.Concentrated filtrate is crossed the macropore resin bed in addition and is analysed post, with 10～40 times of distilled water eluting.Merge (3), (4) water elution liquid, spray drying obtains extract b.
A, b are become the extract of Radix Rhodiolae effective ingredient by 20%: 80% mixed.
Embodiment 7The extraction of Radix Rhodiolae effective ingredient (ethanol refluxing process+water extraction)
A, get Radix Rhodiolae 1500 gram, be ground into coarse powder, with alcohol reflux 2 times, add the alcohol reflux 3 hours of 8 times of amounts 80% for the first time, add the alcohol reflux 3 hours of 10 times of amounts 75% for the 2nd time, medicinal residues keep standby;
B, merge alcohol extract, filter with 400 order filter clothes, precipitation is with 80% washing with alcohol 2 times, filtration, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.15 of simmer down to;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 30 times of distilled water eluting, eluent keeps standby; With 30 times 80% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D, medicinal residues decoct with water 2 times, and each 2 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 3% boils 15min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 10～40 times of distilled water eluting, spray drying obtains extract b;
Extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 30%: 70% mixed.
Embodiment 8The extraction of Radix Rhodiolae effective ingredient (ethanol refluxing process+water extraction)
A, get Radix Rhodiolae 2000 gram, be ground into coarse powder, with 75% alcohol reflux 2 times, each solvent amount is 10 times of Medicinal powder of Rhodiola rosea L., and each 2 hours extraction times, the medicinal residues reservation is standby;
B, merge alcohol extract, filter with 400 order filter clothes, precipitation is with 75% washing with alcohol 3 times, filtration, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.20 of simmer down to;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 20 times of distilled water eluting, eluent keeps standby; With 40 times 80% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D, medicinal residues decoct with water 3 times, and each 3 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 3% boils 30min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 10～40 times of distilled water eluting, spray drying obtains extract b;
Extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 40%: 60% mixed.
Embodiment 9The extraction of Radix Rhodiolae effective ingredient (ethanol refluxing process+water extraction)
A, get Radix Rhodiolae 2500 gram, be ground into coarse powder, with 85% alcohol reflux 3 times, each solvent amount is 8 times of Medicinal powder of Rhodiola rosea L., and each 3 hours extraction times, the medicinal residues reservation is standby;
B, merge alcohol extract, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol 3 times, filtration, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.25 of simmer down to;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 40 times of distilled water eluting, eluent keeps standby; With 30 times 75% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D, medicinal residues decoct with water 3 times, and each 2 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 2% boils 15min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 10～40 times of distilled water eluting, spray drying obtains extract b;
Extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 50%: 50% mixed.
Embodiment 10The extraction of Radix Rhodiolae effective ingredient (ethanol refluxing process+water extraction)
A, get Radix Rhodiolae 3000 gram, be ground into coarse powder, with alcohol reflux 3 times, add the alcohol reflux 2 hours of 10 times of amounts 80% for the 1st, 2 time, add the alcohol reflux 3 hours of 8 times of amounts 75% for the 3rd time, medicinal residues keep standby;
B, merge alcohol extract, filter with 400 order filter clothes, precipitation is with 80% washing with alcohol 2 times, filtration, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.20 of simmer down to;
C, concentrated solution are crossed the macropore resin bed and are analysed post, and earlier with 30 times of distilled water eluting, eluent keeps standby; With 40 times 85% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D, medicinal residues decoct with water 2 times, and each 3 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 4% boils 20min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 20 times of distilled water eluting, spray drying obtains extract b;
Extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 10%: 90% mixed.
Embodiment 11The Radix Rhodiolae preparation of soft capsule
Get the extract a that obtains among the embodiment 1 and the mixture 150g of extract b, join fully to stir among 70 ℃ the vegetable oil 250g and make its dissolving, add soybean lecithin 50g, Cera Flava 20g after the dissolving respectively, polyglycerin ester 30g, fully stirring makes it become mixed uniformly suspension.Suspension is crossed colloid mill, carries out evacuation, pelleting, finalizes the design, washes operations such as ball, drying and obtain 1000 of Radix Rhodiolae soft capsules.Every heavy 0.5g of soft capsule contains the effective ingredient 0.15g that extracts from Radix Rhodiolae.
Embodiment 12The Radix Rhodiolae preparation of soft capsule
Get fully to stir among the mixture 150g of the extract a that obtains among the embodiment 6 and extract b and the vegetable oil 200g that soybean lecithin 40g, polyglycerin ester 20g join 60 ℃ and make its dissolving; To add among 80 ℃ of vegetable oil 70g behind the Cera Flava 20g thermosol in addition.With above-mentioned two kinds of liquid mixing, keep temperature of liquid about 60 ℃～80 ℃, fully stirring makes it become mixed uniformly suspension.Suspension is crossed colloid mill, carries out evacuation, pelleting, finalizes the design, washes operations such as ball, drying and obtain 1000 of Radix Rhodiolae soft capsules.Every heavy 0.5g of soft capsule contains the effective ingredient 0.15g that extracts from Radix Rhodiolae.
Claims (21)
1, a kind of Radix Rhodiolae effective component extracts is characterized in that this extract contains rhodioloside 1～15%, butyl alcohol 0.1～5%, total flavones 10～35%, polysaccharide 25～45%.
2, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 1 is characterized in that this preparation method is:
A. after Radix Rhodiolae is 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;
B. 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 1～3 time, 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;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 75%～85% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
D. after filter cake was dissolved in water, the active carbon of adding 2%～4% filtered with 400 order filter clothes after boiling 15min～30min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by the mixed of 1%～99%:1%～99%.
3, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 2 is characterized in that this preparation 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 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B. add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 80%, left standstill 48 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol 1～3 time, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.20 concentrated solution;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 80% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
D. after filter cake was dissolved in water, the active carbon of adding 4% filtered with 400 order filter clothes after boiling 15min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
The mixed of E. extract a and extract b being pressed 20%:80% promptly gets the Radix Rhodiolae effective component extracts.
4, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 2 is characterized in that this preparation method is:
A. after Radix Rhodiolae is ground into coarse powder, be that aqueous solvent decocts 3 extractions with water, each 2 hours, decocting liquid filtered the back and merges, and was 1.25 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B. add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%, left standstill 48 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 80% washing with alcohol 1～3 time, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.25 concentrated solution;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 75% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
D. after filter cake was dissolved in water, the active carbon of adding 2% filtered with 400 order filter clothes after boiling 15min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 30%: 70% mixed.
5, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 2 is characterized in that this preparation 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 1.30 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B. add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 80%, left standstill 40 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 75% washing with alcohol 1～3 time, 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 concentrated solution;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 80% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
D. after filter cake was dissolved in water, the active carbon of adding 3% filtered with 400 order filter clothes after boiling 20min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 40%: 60% mixed.
6, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 2 is characterized in that this preparation method is:
A. after Radix Rhodiolae is ground into coarse powder, be that aqueous solvent decocts 3 extractions with water, each 1 hour, decocting liquid filtered the back and merges, and was 1.20 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B. add the ethanol mixing in this concentrated solution, 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 80% washing with alcohol 1～3 time, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.20 concentrated solution;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 85% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
D. after filter cake was dissolved in water, the active carbon of adding 4% filtered with 400 order filter clothes after boiling 30min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 50%: 50% mixed.
7, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 2 is characterized in that this preparation method is:
A. after Radix Rhodiolae is ground into coarse powder, be that aqueous solvent decocts 3 extractions with water, each 2 hours, decocting liquid filtered the back and merges, and was 1.25 concentrated solution with 20 ℃ of following relative densities of reclaim under reduced pressure jar simmer down to;
B. add the ethanol mixing in this concentrated solution, adjust to that to contain the alcohol amount be 75%, left standstill 42 hours at 4 ℃～8 ℃, filter with 400 order filter clothes, precipitation is with 85% washing with alcohol 1～3 time, filtration, and the filter cake reservation is standby; Merging filtrate, with ethanol recycling can decompression recycling ethanol, 20 ℃ of following relative densities are 1.25 concentrated solution;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 10～40 times of water gaging eluting, eluent keeps standby; With 75% ethanol elution, alcohol eluen concentrates and reclaims the powder that the ethanol spray drying obtains extract a again;
D. after filter cake was dissolved in water, the active carbon of adding 3% filtered with 400 order filter clothes after boiling 20min, and filtrate is crossed the macropore resin bed in addition and analysed post, with 10～40 times of water elutions; The spray-dried extract b that obtains behind merging, the condensed water eluent;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 10%: 90% mixed.
8, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 1 is characterized in that this preparation method is:
A. Radix Rhodiolae is ground into coarse powder, and with 75%～85% alcohol reflux 1-3 time, each solvent amount is 5～10 times of Medicinal powder of Rhodiola rosea L., and each 1～4 hour extraction time, medicinal residues keep standby;
B. merge alcohol extract, filter with 400 order filter clothes, precipitation filters with 75%～85% washing with alcohol 1～3 time, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.10～1.25 of simmer down to;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 10～40 times of distilled water eluting, eluent keeps standby; With 10～40 times 75%～85% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D. medicinal residues decoct with water 2～3 times, each 1～3 hour, collecting decoction, filter, after boiling 15min～30min, the active carbon that adds filter cake among the B and 2%～4% filters with 400 order filter clothes, concentrated filtrate is crossed the macropore resin bed in addition and is analysed post, merges C, D water elution liquid with 10～40 times of distilled water eluting, and spray drying obtains extract b;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 1%～99%: 1%～99% mixed.
9, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 8 is characterized in that this preparation method is:
A. Radix Rhodiolae is ground into coarse powder, with alcohol reflux 3 times, adds the alcohol reflux 3 hours of 10 times of amounts 75% for the first time, adds the alcohol reflux 2 hours of 8 times of amounts 80% for the 2nd, 3 time, and medicinal residues keep standby;
B. merge alcohol extract, filter with 400 order filter clothes, precipitation filters with 85% washing with alcohol 3 times, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.10 of simmer down to;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 40 times of distilled water eluting, eluent keeps standby; With 40 times 75% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D. medicinal residues decoct with water 3 times, and each 2 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 4% boils 20min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 10～40 times of distilled water eluting, spray drying obtains extract b;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 20%: 80% mixed.
10, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 8 is characterized in that this preparation method is:
A. Radix Rhodiolae is ground into coarse powder, with alcohol reflux 2 times, adds the alcohol reflux 3 hours of 8 times of amounts 80% for the first time, adds the alcohol reflux 3 hours of 10 times of amounts 75% for the 2nd time, and medicinal residues keep standby;
B. merge alcohol extract, filter with 400 order filter clothes, precipitation filters with 80% washing with alcohol 2 times, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.15 of simmer down to;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 30 times of distilled water eluting, eluent keeps standby; With 30 times 80% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D. medicinal residues decoct with water 2 times, and each 2 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 3% boils 15min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 10～40 times of distilled water eluting, spray drying obtains extract b;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 30%: 70% mixed.
11, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 8 is characterized in that this preparation method is:
A. Radix Rhodiolae is ground into coarse powder, and with 75% alcohol reflux 2 times, each solvent amount is 10 times of Medicinal powder of Rhodiola rosea L., and each 2 hours extraction times, medicinal residues keep standby;
B. merge alcohol extract, filter with 400 order filter clothes, precipitation filters with 75% washing with alcohol 3 times, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.20 of simmer down to;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 20 times of distilled water eluting, eluent keeps standby; With 40 times 80% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D. medicinal residues decoct with water 3 times, and each 3 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 3% boils 30min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 10～40 times of distilled water eluting, spray drying obtains extract b;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 40%: 60% mixed.
12, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 8 is characterized in that this preparation method is:
A. Radix Rhodiolae is ground into coarse powder, and with 85% alcohol reflux 3 times, each solvent amount is 8 times of Medicinal powder of Rhodiola rosea L., and each 3 hours extraction times, medicinal residues keep standby;
B. merge alcohol extract, filter with 400 order filter clothes, precipitation filters with 85% washing with alcohol 3 times, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.25 of simmer down to;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 40 times of distilled water eluting, eluent keeps standby; With 30 times 75% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D. medicinal residues decoct with water 3 times, and each 2 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 2% boils 15min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 10～40 times of distilled water eluting, spray drying obtains extract b;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 50%: 50% mixed.
13, the preparation method of a kind of Radix Rhodiolae effective component extracts as claimed in claim 8 is characterized in that this preparation method is:
A. Radix Rhodiolae is ground into coarse powder, uses alcohol reflux 3 times, the alcohol reflux of 10 times of amounts 80% of the 1st, 2 adding 2 hours, and the alcohol reflux of 8 times of amounts 75% of the 3rd adding 3 hours, the medicinal residues reservation is standby;
B. merge alcohol extract, filter with 400 order filter clothes, precipitation filters with 80% washing with alcohol 2 times, and the filter cake reservation is standby; Decompression recycling ethanol, the concentrated solution of 20 ℃ of following relative densities 1.20 of simmer down to;
C. concentrated solution is crossed the macropore resin bed and is analysed post, and earlier with 30 times of distilled water eluting, eluent keeps standby; With 40 times 85% ethanol elution, ethanol elution obtains extract a through concentrated, spray drying again;
D. medicinal residues decoct with water 2 times, and each 3 hours, collecting decoction, filter, filter with 400 order filter clothes after the active carbon that adds filter cake among the B and 4% boils 20min, concentrated filtrate in addition the macropore resin bed analyse post, merge C, D water elution liquid with 20 times of distilled water eluting, spray drying obtains extract b;
E. extract a and extract b are promptly got the Radix Rhodiolae effective component extracts by 10%: 90% mixed.
14,, it is characterized in that containing among the extract a rhodioloside, caffeic acid, butyl alcohol, gallic acid as the preparation method of the described Radix Rhodiolae effective component extracts of claim 2～13.
15, as the described Radix Rhodiolae effective component extracts of claim 2～13 preparation method, it is characterized in that containing Radix Rhodiolae polysaccharide among the extract b.
16, a kind of Radix Rhodiolae soft capsule preparation is characterized in that said preparation is by Radix Rhodiolae effective component extracts 10～25 weight portions, solvent 20～35 weight portions, and stabilizing agent, suspending agent 5～15 weight portions are made; Wherein said extract contains rhodioloside 1～15%, butyl alcohol 0.1～5%, total flavones 10～35%, polysaccharide 25～45%.
17, a kind of Radix Rhodiolae soft capsule preparation as claimed in claim 16 is characterized in that described solvent is vegetable oil, PGE, isopropyl alcohol, glycerol, tween 80, water.
18, a kind of Radix Rhodiolae soft capsule preparation as claimed in claim 16 is characterized in that described stabilizing agent, suspending agent are glycerol, water, soybean lecithin, Cera Flava, aluminum monostearate, ethyl cellulose, solid polyethylene glycol.
19, the preparation method of a kind of Radix Rhodiolae soft capsule preparation as claimed in claim 16 is characterized in that this method is: dissolve in the solvent with 60～80 ℃ of extract addings; Add stabilizing agent, suspending agent again, after stirring suspension is crossed colloid mill, degassing evacuation, is washed ball, drying at pelleting, promptly gets the Radix Rhodiolae soft capsule.
20, the preparation method of a kind of Radix Rhodiolae soft capsule preparation as claimed in claim 19 is characterized in that this method is:
70 ℃ of vegetable oil 25 weight portions of Radix Rhodiolae effective component extracts 15 weight portions
Soybean lecithin 5 weight portion Cera Flavas 2 weight portion polyglycerin ester 3 weight portions
Get the Radix Rhodiolae effective component extracts, join fully to stir in 70 ℃ the vegetable oil and make its dissolving, add soybean lecithin after the dissolving respectively, Cera Flava, polyglycerin ester fully stirs and makes it become mixed uniformly suspension; Suspension is crossed colloid mill, carries out evacuation, pelleting, finalizes the design, washes ball, is drying to obtain the Radix Rhodiolae soft capsule.
21, the preparation method of a kind of Radix Rhodiolae soft capsule preparation as claimed in claim 19 is characterized in that this method is:
Radix Rhodiolae effective component extracts 15 weight portion soybean lecithins 4 weight portions
Vegetable oil 20 weight portions that polyglycerin ester 2 weight portions are 60 ℃
80 ℃ of vegetable oil 7 weight portions of Cera Flava 2 weight portions
Get fully to stir in the vegetable oil that Radix Rhodiolae effective component extracts and soybean lecithin, polyglycerin ester join 60 ℃ and make its dissolving; To add behind the Cera Flava thermosol in 80 ℃ of vegetable oil in addition; With two kinds of liquid mixing, keep temperature of liquid about 60 ℃～80 ℃, fully stirring makes it become mixed uniformly suspension; Suspension is crossed colloid mill, carries out evacuation, pelleting, finalizes the design, washes ball, is drying to obtain the Radix Rhodiolae soft capsule.
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| CN 200410037407 CN1268323C (en) | 2004-04-30 | 2004-04-30 | Rhodiola sacra soft capsule and its preparation |
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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 |
| CN100391484C (en) * | 2005-11-23 | 2008-06-04 | 西藏诺迪康药业股份有限公司 | Medicine for treating cardio-cerebrovascular disease |
| CN102485267A (en) * | 2008-04-10 | 2012-06-06 | 羊敏 | Tibetan-Miao medicine for treating child cough caused by allergy, viruses, and bacteria |
| CN101732394A (en) * | 2008-11-07 | 2010-06-16 | 羊敏 | Tibetan medicament for treating depression and phrenesis (schizophrenia) and preparation method thereof |
| CN101766670B (en) * | 2010-02-23 | 2012-05-23 | 上海应用技术学院 | Rhodiola rosea polyphenol microcapsule and preparation method |
| CN109007934A (en) * | 2018-07-03 | 2018-12-18 | 广州普正生物科技有限公司 | A kind of ultra micro suspension system |
| CN110063978B (en) * | 2019-05-15 | 2021-10-01 | 青海普兰特药业有限公司 | Rhodiola rosea formula granule, preparation method and detection method thereof |
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