CN100393319C - Astragaloside cyclodextrin clathrate, its prepn. and preparing mehtod - Google Patents
Astragaloside cyclodextrin clathrate, its prepn. and preparing mehtod Download PDFInfo
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- CN100393319C CN100393319C CNB200510095308XA CN200510095308A CN100393319C CN 100393319 C CN100393319 C CN 100393319C CN B200510095308X A CNB200510095308X A CN B200510095308XA CN 200510095308 A CN200510095308 A CN 200510095308A CN 100393319 C CN100393319 C CN 100393319C
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- astragaloside
- cyclodextrin
- clathrate
- combination
- beta
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- SMDOOINVMJSDPS-UHFFFAOYSA-N Astragaloside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)=C1 SMDOOINVMJSDPS-UHFFFAOYSA-N 0.000 title claims abstract description 100
- QMNWISYXSJWHRY-XWJCTJPOSA-N astragaloside Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)C4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)CC3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-XWJCTJPOSA-N 0.000 title claims abstract description 100
- 229920000858 Cyclodextrin Polymers 0.000 title claims abstract description 51
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title claims abstract description 48
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- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
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- QMNWISYXSJWHRY-YLNUDOOFSA-N astragaloside IV Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)[C@H]4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C[C@H]3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-YLNUDOOFSA-N 0.000 description 1
- QMNWISYXSJWHRY-BCBPIKMJSA-N astragaloside IV Natural products CC(C)(O)[C@@H]1CC[C@@](C)(O1)[C@H]2[C@@H](O)C[C@@]3(C)[C@@H]4C[C@H](O[C@@H]5O[C@H](CO)[C@H](O)[C@@H](O)[C@H]5O)[C@H]6C(C)(C)[C@H](CC[C@@]67C[C@@]47CC[C@]23C)O[C@@H]8OC[C@@H](O)[C@H](O)[C@H]8O QMNWISYXSJWHRY-BCBPIKMJSA-N 0.000 description 1
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Abstract
The present invention relates to the field of a medicinal preparation, particularly to a cyclodextrin inclusion compound of astragaloside used as a natural medicine, a preparation and a preparation method thereof. The present invention makes the dissolvability increased from 22.2 mug/ml to 188.4 to 386.8 mug/ml by making the astragaloside included by cyclodextrin, and biological availability is increased from 3% to 11%.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to cyclodextrin clathrate, preparation of natural drug astragaloside and preparation method thereof.
Background technology
Radix Astragali Astragalus membranacevs (Fisch.) Bge.Var.mongolicus (Bge.) Hsiao is a conventional Chinese medicine, main product in Shanxi, ground such as Gansu, Heilungkiang, the Inner Mongol, have invigorating QI to consolidate the body surface resistance, diuresis poison holding, evacuation of pus, the effect of expelling pus and promoting granulation.Astragaloside is the main active in the Radix Astragali, English Astragaloside IV by name, and its molecular formula is C
41H
68O
14Modern pharmacology and Chemistry for Chinese Traditional Medicine studies show that, astragaloside has the enhancing human body immunity function, and antiinflammatory strengthens the heart positive inotropic action, multiple pharmacological effect such as blood pressure lowering, the clinical qi depression to blood stasis cardiovascular and cerebrovascular disease that is used for the treatment of as insufficiency of heart-QI damage, blood-vessel obstructive, viral myocarditis, cardiac insufficiency, the insufficiency of the spleen treatment that is stranded wet hepatitis, also can be used as tumor, the auxiliary treatment of immunologic hypofunction etc., evident in efficacy, be a kind of extremely promising medicine, have great exploitation and be worth.
The extracting method of the astragaloside of bibliographical information has multiple, as " extraction process of astragaloside in the Radix Astagali " (Yuan Tianshuo " medical Leader " the 24th the 7th phase of volume of July in 2005) etc.Because astragaloside dissolubility in water is very little, so oral administration biaavailability is very low, is difficult to be prepared into injection simultaneously, therefore limited being extensive use of of it.
Summary of the invention
The present invention uses modern galenic pharmacy technology, adopt novel enclose rings of material dextrin or derivatives thereof that its enclose is formed the astragaloside cyclodextrin clathrate, improved dissolubility and the bioavailability of astragaloside in water greatly, and make various dosage forms, enrich the preparation variety of this class medicine, expanded the application prospect of astragaloside.
Technical scheme of the present invention is as follows:
Astragaloside combination of the present invention is mixed and made into pharmaceutic adjuvant after it is characterized in that astragaloside and cyclodextrin made cyclodextrin clathrate again.
Among the present invention, described astragaloside can be a monomer component, also can be to be the Radix Astragali extract of main component with the astragaloside.If Radix Astragali extract, then Astragaloside content surpasses 40%, and extract also contains the mixture of some other saponin, flavone, polysaccharide, aminoacid etc.
Similarly, cyclodextrin derivative such as the preferred beta-schardinger dextrin-of cyclodextrin of the present invention, HP-, hydroxyethyl-, methyl-beta-schardinger dextrin-, sulfonic acid group-beta-cyclodextrin, glucose group-beta-cyclodextrin.Further preferably beta-schardinger dextrin-or HP-.
Described pharmaceutic adjuvant can be one or more in diluent, disintegrating agent, binding agent, wetting agent, lubricant, excipient, the slow-release material.Used pharmaceutic adjuvant is according to the dosage form selection corresponding medicinal adjuvant that will prepare.
Wherein diluent is selected from one or more in starch, lactose, amylum pregelatinisatum, the microcrystalline Cellulose; Disintegrating agent is selected from one or more in dried starch, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, the polyvinylpolypyrrolidone; Binding agent is selected from one or more in starch slurry, polyvidone, the sodium carboxymethyl cellulose; Wetting agent is water or starch slurry; Lubricant is magnesium stearate or Pulvis Talci; Excipient is selected from one or more in mannitol, dextran, the sorbitol; Slow-release material is selected from one or more in hydroxypropyl emthylcellulose, methylcellulose, hydroxyethyl-cellulose or the sodium carboxymethyl cellulose.
The preparation method of astragaloside combination of the present invention, make the astragaloside cyclodextrin clathrate earlier: astragaloside is dissolved in methanol or the ethanol, cyclodextrin is soluble in water, under the heated and stirred or heat and ultrasonicly down the astragaloside alcoholic solution is added drop-wise in the cyclodextrin solution, cooling, drying promptly gets clathrate.Again clathrate and pharmaceutic adjuvant are mixed and made into various dosage forms.Dosage form can be multiple, as: tablet, capsule, granule, pill, drop pill, mixture, injection, aseptic powder injection, freeze-dried powder, transfusion, suppository or spray etc.
In the above-mentioned preparation method, the used weight ratio of astragaloside and cyclodextrin is preferably 1: 1～and 20.
The used weight ratio of preferred astragaloside and cyclodextrin is 1: 2～8.
Heating-up temperature is preferably 30～60 ℃ in the above-mentioned preparation method.Temperature and methanol and ethanol are volatile owing to have a surplus, and therefore, under the condition of not heating, continuation stirring or ultrasonic energy make solvent evaporates, solution concentration after the astragaloside alcoholic solution drips.Preferably work as solution concentration to remaining 1/20 to 1/3 original volume, stop stirring or ultrasonic, carry out drying, promptly get clathrate.
In the technology of preparing of cyclodextrin clathrate, the general saturated water solution method that adopts, enclose needs operations such as cold preservation is spent the night, filtration, washing, drying after finishing, and need not cold preservation, filtration and washing behind this technology enclose, only need the dry solvent of removing to get final product, simplified the enclose preparation process greatly.
Drying means can adopt drying meanss such as oven drying method, hypobaric drying method, freeze-drying or spray drying method, preferably drying under reduced pressure.
Astragaloside is insoluble in water, and dissolubility is about 22.2 μ gml in the water
-1After astragaloside was prepared into clathrate with cyclodextrin, dissolubility was significantly improved.When the weight ratio of cyclodextrin or derivatives thereof and astragaloside is 1～20: 1 when carrying out enclose, the dissolubility of gained astragaloside cyclodextrin clathrate is 80.5～386.8 μ gml
-1, average dissolubility is 223.1 μ gml
-1, bioavailability brings up to 11.6% by 3.0%; And when the weight ratio of cyclodextrin or derivatives thereof and astragaloside be 2～8: 1 when carrying out enclose, the dissolubility of clathrate is 188.4～365.7 μ gml
-1, average dissolubility 306.1 μ gml
-1, bioavailability brings up to 18.0%.
Be partial solubility test and the data behind different cyclodextrin of the present invention and the astragaloside ratio enclose below:
Weight ratio with different cyclodextrin and astragaloside prepares clathrate according to described preparation method.Take by weighing excessive clathrate, add 2ml through boiling and putting cold distilled water, the vortex vibration is also placed 2h under 25 ± 2 ℃, and the centrifuging and taking supernatant filters with 0.45 μ m microporous filter membrane, measures its dissolubility.The results are shown in Table 1:
The cyclodextrin that table 1 is different: reach former medicine dissolubility behind the astragaloside ratio enclose
| Rate of charge | Former medicine | 0.5∶1 | 1∶1 | 1.5∶1 | 2∶1 | 4∶1 | 8∶1 | 15∶1 | 20∶1 |
| Dissolubility (μ gml -1) | 22.2 | 38.1 | 80.5 | 93.7 | 188.4 | 329.5 | 356.9 | 350.4 | 359.0 |
By table 1 data as seen, the weight ratio of cyclodextrin and astragaloside is 1～20: dissolubility helps improving its bioavailability obviously greater than former medicine in 1 scope.Again because 1～2: dissolubility is significantly less than 2～8 in 1 scope: the dissolubility in 1 scope, and no longer obviously increase greater than 8: 1 back dissolubility, substantially maintain fluctuation up and down in the scope, and too much cyclodextrin content can cause content of dispersion to descend, so preferred ratio is 2～8: 1.
We also contrast astragaloside clathrate of the present invention and former medicine dissolution, and method is:
Got two kinds of astragaloside clathrates an amount of (containing astragaloside 30mg) and the former medicine 30mg of astragaloside of 60 mesh sieves, and be divided into 6 parts respectively, and measured according to the slurry method, dissolution medium is that (no enzyme, pH7.5) 900ml, rotating speed are 100rmin to the simulated intestinal fluid of handling through the degassing
-1, water temperature is 37 ± 0.5 ℃.Respectively 5,10,20,40,70,100, draw solution is an amount of during 160min, filters with 0.8 μ m microporous filter membrane immediately, adds the equivalent fresh medium simultaneously, sample calculates the accumulation dissolution of different time after measured behind the content, and the result shows the dissolution rate of astragaloside clathrate dissolution rate of the present invention apparently higher than the former medicine of astragaloside.Partial data sees Table 2 and Fig. 1:
Former medicine of table 2 astragaloside and astragaloside clathrate accumulation stripping percentage ratio (%)
| Sample | 5min | 10min | 20min | 40min | 70min | 100min | 160min |
| Former medicine | 1.14 | 9.32 | 24.81 | 50.85 | 65.43 | 78.01 | 88.50 |
| Clathrate 1 | 12.86 | 27.80 | 51.44 | 68.31 | 78.25 | 84.20 | 92.27 |
| Clathrate 2 | 27.71 | 55.03 | 72.32 | 81.82 | 88.50 | 95.33 | 98.79 |
Clathrate 1 is the astragaloside cyclodextrin clathrate of embodiment 4 methods preparation, and clathrate 2 is the astragaloside cyclodextrin clathrate of embodiment 5 methods preparation.
The bioavailability test:
Experimental technique: with SD rat (190-210g) is laboratory animal, and adaptability is raised a week, is divided into matched group and experimental group at random, 6 every group.The oral former medicine of astragaloside of giving of matched group, experimental group is single dose 20mgkg with the oral clathrate (according to the preparation of embodiment 6 methods) of giving of method
-1,, got blood in 6,8,12 and 24 hours respectively at after the administration 0.25,0.5,0.75,1,1.5,2,3,4.Blood sample is measured the blood drug level under each time after treatment, calculates oral administration AUC
TFormer medicine is intravenous administration (single dose 1.5mgkg in kind
-1), measure the blood drug level of each time point, calculate quiet notes administration AUC with method
Iv, and by following formula calculating oral administration bioavailability F.Wherein D is a dosage.
Prepared clathrate oral administration bioavailability can reach 18.0%, can satisfy the clinical treatment needs.And the bioavailability of former medicine oral administration only is 3.0%.
The made astragaloside cyclodextrin clathrate of the present invention can be prepared into various dosage forms, as oral formulations (comprising tablet, capsule, granule, pill, mixture, drop pill etc.), injection (comprising injection, aseptic powder injection or freeze-dried powder and transfusion etc.) also can be made into suppository, spray etc.
If be prepared into oral formulations, can contain pharmaceutic adjuvants such as starch, lactose, amylum pregelatinisatum, Icing Sugar, hydroxypropyl emthylcellulose, microcrystalline Cellulose, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, polyvinylpolypyrrolidone, methylcellulose, hydroxyethyl-cellulose, sodium carboxymethyl cellulose, polyvidone, magnesium stearate, Pulvis Talci.
Injection of the present invention gets through preparation mainly by astragaloside cyclodextrin clathrate and water for injection.
If be prepared into injection, can also add antioxidant, antioxidant is sodium sulfite, sodium pyrosulfite, sodium thiosulfate, disodiumedetate, cysteine etc.
In the injection of the present invention, can contain the excipient of 3-20%, as in mannitol, dextran, the sorbitol one or more.
Be prepared into freeze-dried powder mainly by astragaloside cyclodextrin clathrate and proppant or excipient, get by lyophilization.
Be prepared into aseptic powder injection mainly by astragaloside cyclodextrin clathrate and suitable proppant or excipient, the powder that obtains by lyophilization or spray drying carries out aseptic subpackaged getting.
When being prepared into when transfusion, mainly ooze thing by astragaloside cyclodextrin clathrate, water for injection and an amount of etc., ooze instrumentality as acceptable etc. on sodium chloride, glucose and other pharmaceuticss, get through preparation.
The invention solves the very little problem of astragaloside dissolubility in water, stability improves.Astragaloside clathrate of the present invention can be used for making various preparations, has advantage efficiently.Made oral formulations has bioavailability height, characteristics safely and efficiently; Made injection need not to add solubilizing agents such as organic solvent or surfactant, and medicament contg height, good effect, advantage that toxic and side effects is low.It is easy that the present invention prepares the astragaloside clathrate means, can control automatically, is easy to industrialization.
Description of drawings
Fig. 1 is former medicine of astragaloside and astragaloside clathrate stripping curve
The specific embodiment
Embodiment 1
The preparation of astragaloside Benexate Hydrochloride
Take by weighing astragaloside 5.0g, add the heating of 1250ml ethanol and make its dissolving; Other takes by weighing beta-schardinger dextrin-7.2g and adds the 360ml distilled water, the heated and stirred dissolving; Stir and slowly drip the astragaloside alcoholic solution down, holding temperature continues to stir half an hour at 50 ℃, stops heating, makes it be reduced to room temperature gradually, continues to be stirred to solution residue 1/5, drying under reduced pressure, promptly.This clathrate dissolubility reaches 82.5 μ g/ml.
Embodiment 2
The preparation of astragaloside Benexate Hydrochloride
Take by weighing astragaloside 5.0g, add the heating of 950ml methanol and make its dissolving; Other takes by weighing beta-schardinger dextrin-7.2g and adds 360ml distilled water, heating for dissolving; The ultrasonic astragaloside methanol solution that drips down slowly, holding temperature continues ultrasonic half an hour at 40 ℃, stops heating, makes it be reduced to room temperature gradually, continues ultrasonicly to remain 1/5 to solution, drying under reduced pressure, promptly.This clathrate dissolubility reaches 80.9 μ g/ml.
Embodiment 3
The preparation of astragaloside Benexate Hydrochloride
Take by weighing astragaloside 5.0g, add about 1250ml ethanol heating and make its dissolving; Other takes by weighing beta-schardinger dextrin-14.4g and adds the 720ml distilled water, the heated and stirred dissolving; Stir and slowly drip the astragaloside alcoholic solution down, holding temperature continues to stir 1 hour at 50 ℃, stops heating, makes it be reduced to room temperature gradually, continues to be stirred to solution residue 1/10, drying under reduced pressure, promptly.This clathrate dissolubility reaches 195.6 μ g/ml.
Embodiment 4
The preparation of astragaloside hydroxypropyl-beta-cyclodextrin inclusion
Take by weighing astragaloside 5.0g, add about 1250ml ethanol heating and make its dissolving; Other takes by weighing HP-8.0g and adds the 40ml distilled water, the heated and stirred dissolving; Stir and slowly drip the astragaloside alcoholic solution down, holding temperature continues to stir 1 hour at 50 ℃, stops heating, makes it be reduced to room temperature gradually, continues to be stirred to solution residue 1/5, drying under reduced pressure, promptly.This clathrate dissolubility reaches 120.3 μ g/ml.
Embodiment 5
The preparation of astragaloside hydroxypropyl-beta-cyclodextrin inclusion
Take by weighing astragaloside 5.0g, add about 1250ml ethanol heating and make its dissolving; Other takes by weighing HP-20.0g and adds the 80ml distilled water, the heated and stirred dissolving; Stir and slowly drip the astragaloside alcoholic solution down, holding temperature continues to stir 1 hour at 50 ℃, stops heating, makes it be reduced to room temperature gradually, continues to be stirred to solution residue 1/10, drying under reduced pressure, promptly.This clathrate dissolubility reaches 329.5 μ g/ml.
Embodiment 6
The preparation of astragaloside hydroxypropyl-beta-cyclodextrin inclusion
Take by weighing astragaloside 5.0g, add about 1250ml ethanol heating and make its dissolving; Other takes by weighing HP-40.0g and adds the 160ml distilled water, the heated and stirred dissolving; Stir and slowly drip the astragaloside alcoholic solution down, holding temperature continues to stir 1 hour at 50 ℃, stops heating, makes it be reduced to room temperature gradually, continues to be stirred to solution residue 1/10, drying under reduced pressure, promptly.This clathrate dissolubility reaches 356.9 μ g/ml.
Embodiment 7
The preparation of astragaloside hydroxypropyl-beta-cyclodextrin inclusion
Take by weighing astragaloside 5.0g, add the heating of 1250ml ethanol and make its dissolving; Other takes by weighing HP-75.0g and adds the 300ml distilled water, the heated and stirred dissolving; Under agitation slowly drip the astragaloside alcoholic solution, holding temperature continues to stir 1 hour at 50 ℃, stops heating, makes it be reduced to room temperature gradually, continues to be stirred to solution residue 1/10, drying under reduced pressure, promptly.This clathrate dissolubility reaches 350.4 μ g/ml.
Embodiment 8
Astragaloside cyclodextrin clathrate tablet
Take by weighing 30.0g astragaloside cyclodextrin clathrate (embodiment 5 methods make), add 6.8g starch, mixing drips 10% starch slurry, make soft material, cross 14 mesh sieves and granulate, 16 mesh sieve granulate are crossed in 70 ℃ of oven dry, add 1% magnesium stearate tabletting, make 100 altogether, get tablet.
Embodiment 9
Astragaloside cyclodextrin clathrate capsule
Take by weighing 30.0g astragaloside cyclodextrin clathrate (embodiment 5 methods make), encapsulated with 10.0g starch mixing, totally 100, get capsule.
Embodiment 10
Astragaloside cyclodextrin clathrate slow releasing tablet
Take by weighing 30.0g astragaloside cyclodextrin clathrate (embodiment 5 methods make), add 1.0g starch, the 6.0g hydroxypropyl emthylcellulose, mixing, drip 10% starch slurry, make soft material, cross 14 mesh sieves and granulate, 70 ℃ of oven dry, cross 16 mesh sieve granulate, add 1% magnesium stearate mix homogeneously, tabletting, make 100 altogether, promptly get slow releasing tablet.
Embodiment 11
Astragaloside cyclodextrin inclusion compound composition injection
Get the hot water for injection of about 800ml, add 0.72g astragaloside cyclodextrin clathrate (embodiment 6 methods make) and 9.0g sodium chloride, stirring makes dissolving, add 0.15% activated carbon decolorizing again, be filtered to clear and brightly, add water for injection to 1000ml, embedding is in the 200ml infusion bottle, in 115 ℃ of pressure sterilizing 30min, promptly get and infuse.
Claims (8)
1. astragaloside combination, be mixed and made into pharmaceutic adjuvant again after it is characterized in that astragaloside and cyclodextrin made cyclodextrin clathrate, wherein the used weight ratio of astragaloside and cyclodextrin is 1: 1～1: 20, made by following method: astragaloside is dissolved in methanol or the ethanol, cyclodextrin is soluble in water, under the heated and stirred or heat and ultrasonicly down the astragaloside alcoholic solution is added drop-wise in the cyclodextrin solution, cooling, dry, promptly get clathrate, described astragaloside is monomer component or is the Radix Astragali extract of main component with the astragaloside.
2. the astragaloside combination of claim 1, wherein cyclodextrin is beta-schardinger dextrin-, HP-, hydroxyethyl-, methyl-beta-schardinger dextrin-, sulfonic acid group-beta-cyclodextrin, glucose group-beta-cyclodextrin.
3. the astragaloside combination of claim 2, wherein cyclodextrin is beta-schardinger dextrin-or HP-.
4. the astragaloside combination of claim 1, wherein pharmaceutic adjuvant is selected from one or more in diluent, disintegrating agent, binding agent, wetting agent, lubricant, excipient, the slow-release material.
5. the astragaloside combination of claim 4, wherein diluent is selected from one or more in starch, lactose, amylum pregelatinisatum, the microcrystalline Cellulose; Disintegrating agent is selected from one or more in dried starch, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, the polyvinylpolypyrrolidone; Binding agent is selected from one or more in starch slurry, polyvidone, the sodium carboxymethyl cellulose; Wetting agent is water or starch slurry; Lubricant is magnesium stearate or Pulvis Talci; Excipient is selected from one or more in mannitol, dextran, the sorbitol; Slow-release material is selected from one or more in hydroxypropyl emthylcellulose, methylcellulose, hydroxyethyl-cellulose or the sodium carboxymethyl cellulose.
6. the astragaloside combination of claim 1, wherein the used weight ratio of astragaloside and cyclodextrin is 1: 2～1: 8.
7. the astragaloside combination of claim 1 wherein is mixed and made into tablet, capsule, granule, pill, drop pill, mixture, injection, aseptic powder injection, freeze-dried powder, transfusion, suppository or spray with clathrate and pharmaceutic adjuvant.
8. the astragaloside combination of claim 1, wherein heating-up temperature is 30～60 ℃, and the astragaloside alcoholic solution drips that the back continue to be stirred or be ultrasonic when remaining 1/20 to 1/3 original volume to solution, stops to stir or ultrasonic, cool drying promptly gets clathrate, and wherein drying is a drying under reduced pressure.
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| CN101007012B (en) * | 2006-01-23 | 2011-03-23 | 天津药物研究院 | An oral mucosal absorbent preparation containing active components of astragaloside IV |
| CN101502558B (en) * | 2009-03-21 | 2011-05-11 | 山西振东泰盛制药有限公司 | Method for preparing astragalus total saponin injection from cyclodextrin composition |
| CN106511562A (en) * | 2017-01-12 | 2017-03-22 | 卢正良 | Traditional Chinese medicine for treating cardiovascular diseases |
| CN108077579A (en) * | 2017-12-21 | 2018-05-29 | 成都欣牧生物科技有限公司 | A kind of Chinese herbal feed additive for improving livestock and poultry production performance and its preparation method and application |
| CN112107541B (en) * | 2019-06-21 | 2023-07-25 | 陕西中医药大学 | Astragaloside IV self-emulsifying drug release system and preparation method thereof |
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| JPH08510474A (en) * | 1994-03-16 | 1996-11-05 | ベルビィ・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | Method of using triterpene saponins such as notodine cenoside R1 (NR1) and / or astragalside (ASIV) in the manufacture of a medicament |
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