CN103239398B - Dammarane sapogenin suspension, and preparation method and application thereof - Google Patents
Dammarane sapogenin suspension, and preparation method and application thereof Download PDFInfo
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- CN103239398B CN103239398B CN201210022860.6A CN201210022860A CN103239398B CN 103239398 B CN103239398 B CN 103239398B CN 201210022860 A CN201210022860 A CN 201210022860A CN 103239398 B CN103239398 B CN 103239398B
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Abstract
The invention relates to a dammarane apogenin suspension, and a preparation method and an application thereof. The dammarane apogenin suspension comprises 10-60wt% of dammarane apogenin, 2-15wt% of a hydrophilic auxiliary material, phosphatides, and the balance water, wherein the weight ratio of phosphatides to the dammarane apogenin is 1:500-1:20, and the weight percentage of dammarane apogenin is 30-50%. No organic solvent is used in the preparation method of the dammarane apogenin suspension, so the residual problem of the organic solvent is avoided, and the drug loading capacity is high; the preparation method is convenient and simple, so it in benefit for the industrialized production; and the dammarane apogenin suspension is laminated to the surface of a blank pill to prepare a tablet or a capsule, so the absorption effect is good.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to Radix Ginseng dammarane aglycon grinding suspension and preparation method thereof and the application in pharmaceutical preparation.
Background technology
Ginsenoside is a kind of steroid compound, triterpene saponin, the main active of extracting from the root of Araliaceae Radix Ginseng, stem, leaf.There is the quantity of leucocyte of increasing, improve body immunity, promote substance metabolism, resisting fatigue, the anti-ageing effect of waiting for a long time.But due to the common slightly solubility of Chinese medicine, ginsenoside's dissolubility is poor, and absorption is also poor in vivo, thereby causes ginsenoside's bioavailability in vivo lower.
Domestic about improving the patent of ginsenoside's bioavailability few, and rare several parts of patents also be mostly to prepare liquid preparation, the patent that improves bioavailability about solid preparation is rarely found.
CN101530389 discloses a kind of ginsenoside Rg 3 and phospholipid complex and preparation method thereof.Preparation method adopts little organic solvent dissolution ginsenoside Rg3 and the mixture of phospholipids of dielectric constant, through technical processs such as evaporating solvents, makes ginsenoside Rg 3 and phospholipid complex.Ginsenoside Rg 3 and phospholipid complex has fat-soluble, and human body easily absorbs, thereby has improved its bioavailability.But the organic solvent using in this patent is difficult to remove completely, residual solvent may produce harmful effect to human body.
CN1626101 provides nano-emulsion of ginsenoside and its production and use.Ginsenoside's Emulsion that this patent provides contains ginsenoside, water, and oil, tune isotonic agent and surfactant, can also contain stabilizing agent.This Emulsion improves the bioavailability of medicine by changing the distribution of saponin in human body, and then improves curative effect of medication.But the drug loading of nano-emulsion is low, be unfavorable for taking in a large number, and the complicated process of preparation of Emulsion, make troubles to a large amount of production.
The invention provides a kind of method of new raising dissolution: adopt suspension grinding technique to process Radix Ginseng dammarane aglycon.Radix Ginseng dammarane aglycon is added to lapping device with the suspension with the hydrophilicity condiment of certain viscosity, such as being equipped with glass, zirconium oxide bead or making such as polymer such as polystyrene derivatives in the grinding container of ball milling ball, the suction of self-priming impeller high speed, in mill basket by the superfine grinding of import zirconium oxide bead, at dispersion impeller high speed rotating, produce dispersion, mixing, cyclical effect, form thus the high efficiency circulation of suction, grinding, discharging, in the short time, just can obtain outstanding grinding effect.The centrifugal force that grinding suspension produces while being subject to high speed rotating simultaneously, the abrasive power of zirconia ball and shearing force, three power cooperate jointly by the abundant micronization of medicine, and particle diameter can reach several microns.It by reduce medicine particle diameter, increase surface area, improve the stripping that the effects such as wettability promote medicines, be the very effective approach that increases insoluble drug dissolution rate.With agitator, promote ball (globule), medicine is ground into nano-particle between the ball rolling, this medicament nano granule of preparing with agitator ball-milling method is less than 500nm, by the abundant micronization of medicine, by hydrophilic high molecular material, wrapped and keep apart simultaneously, prevent the coalescent and possible surface adsorption of small drug particle after micronization, thereby increase the dissolution of medicine, finally form the medicine aqueous dispersion as nano-particle aqueous colloidal dispersion, then further make the preparation of various route of administration.The method not with an organic solvent, has been avoided organic solvent residual problem, and drug loading is high, and production technology is convenient and simple, is beneficial to suitability for industrialized production, and therefore, the method has good prospect of production.
Summary of the invention
The object of the present invention is to provide a kind of effective method of improving the stripping of Radix Ginseng dammarane aglycon and improving its bioavailability.Described method comprises Radix Ginseng dammarane aglycon joined in the aqueous solution containing the hydrophilicity condiment of phospholipid, and grinds in grinder, to make Radix Ginseng dammarane aglycon grinding suspension.The advantage of the inventive method is as follows: by the abundant micronization of medicine, by hydrophilic high molecular material, wrapped and keep apart simultaneously, prevent the coalescent and possible surface adsorption of small drug particle after micronization, thereby increase the dissolution of medicine, finally form the medicine aqueous dispersion as nano-particle aqueous colloidal dispersion, further make the preparation of various route of administration.Particular content is as follows:
A kind of dammarane's aglycon suspension, described dammarane's aglycon suspension comprises the component of following percentage by weight: dammarane's aglycon 10～60%, hydrophilicity condiment 2～15% and the phospholipid that is 1:500～1:20 with the weight ratio of described dammarane's aglycon, other are water.
The percentage by weight of described dammarane's aglycon is 30～50%.
The percentage by weight of described hydrophilicity condiment is 3～8%, is selected from one or more in cellulose derivative, polyvinylpyrrolidone (PVP), gelatin and xanthan gum.Described cellulose derivative is as hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxy methocel (HMC).Preferably, described hydrophilicity condiment is HPMC.
The weight ratio of described phospholipid and described dammarane's aglycon is 1:200～1:50.
The particle diameter of described dammarane's aglycon is less than 500nm.
The preparation method of above-mentioned arbitrary described dammarane's aglycon suspension, comprises the steps:
(1) phospholipid is dispersed in hydrophilicity condiment aqueous solution, then adds dammarane's aglycon of first batch, under grinder, grind, milling time is 0.5～3 hour;
(2) add dammarane's aglycon of remaining batch, the operation of repeating step (1), the percentage by weight of final described dammarane's aglycon is 10～60%, the percentage by weight of described hydrophilicity condiment is 2～15%, and the weight ratio of described phospholipid and described dammarane's aglycon is 1:500～1:20.
The rotating speed of described grinder is 1200～1800 rmin
-1.
The application of above-mentioned dammarane's aglycon suspension, makes tablet or capsule by described dammarane's aglycon suspension lamination to the surface of blank pill, and described blank pill is microcrystalline Cellulose ball, sucrose ball or starch ball.
Described tablet or capsule also comprise excipient substance, and described excipient substance is filler, disintegrating agent and lubricant;
Described filler is selected from one or more in starch, dextrin, lactose, mannitol and microcrystalline Cellulose, and the weight percent that accounts for described tablet or capsule is 40～70%;
Described disintegrating agent is selected from one or more in cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and sodium lauryl sulphate, and the weight percent that accounts for described tablet or capsule is 10～20%;
Described lubricant is selected from one or more in magnesium stearate, Pulvis Talci, and the weight percent that accounts for described tablet or capsule is 3～7%.
Preferably, Radix Ginseng dammarane aglycon is to join in the aqueous solution of hydrophilicity condiment in batches, that is to say and adds a collection of Radix Ginseng dammarane aglycon, then grinds, and adds afterwards a collection of Radix Ginseng dammarane aglycon again, continues to grind.The advantage of this batch charging is to prevent that suspension viscosity when grinding is excessive.
Preferably, in the dammarane's aglycon grinding suspension after grinding, dammarane's aglycon particle diameter is less than 500nm.
Preferably, described grinding is with 1500 rmin
-1in the basket-type grinder running up, carry out, the described grinding time of carrying out is 0.5～3 hour, and preferred described milling time is 1 hour.
The invention provides the Radix Ginseng dammarane aglycon grinding suspension of preparing by said method.
The present invention also provides pharmaceutical preparation, and described pharmaceutical preparation is made with above-mentioned dammarane's aglycon grinding suspension and excipient substance.Pharmaceutical preparation comprises tablet and capsule.Preferably, described pharmaceutical preparation is tablet.More preferably, described tablet is quick-release tablet.The adjuvant that described quick-release tablet is used is filler, disintegrating agent and lubricant.Described filler is selected from one or more in starch, dextrin, lactose, mannitol and microcrystalline Cellulose (MCC).Described disintegrating agent is selected from one or more in cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and sodium lauryl sulphate.Described lubricant is selected from one or more in magnesium stearate and Pulvis Talci.
With respect to general drug micronization technology, this liquid feeding is sheared grinding technique can allow micronized medicine have more superior stability.Meanwhile, the medicinal liquid after liquid feeding grinds directly can carry out Downstream processing, can be made into the multiple dosage forms such as fast-release tablet, quick-release capsules.It can be seen, the downstream processing step that the medicinal liquid after liquid feeding is ground carries out is simple, easy to operate, convenient and time-saving, has unrivaled superiority.
Accompanying drawing explanation
Fig. 1 is the particle size determination scattergram of dammarane's aglycon suspension under each milling time.
The specific embodiment
Below, by following examples, the invention will be further described, and it will contribute to understand the present invention, but not limit content of the present invention.
In a specific embodiments, phospholipid is dispersed in hydrophilicity condiment solution, then mix according to a certain percentage with Radix Ginseng dammarane aglycon powder.Preparation process Chinese medicine adds in aqueous solution several times, can prevent that viscosity is excessive when suspension grinds, and preferably divides four times and adds.The ultimate density of hydrophilicity condiment is 3～8%.
Described hydrophilicity condiment comprises: cellulose derivative (as HPMC, HPC, HMC), PVP, PEG, gelatin, xanthan gum etc., preferably HPMC, PVP and HPC, wherein for the preferred HPMC of Radix Ginseng dammarane aglycon fast-release tablet.
In the Radix Ginseng dammarane aglycon grinding suspension making, the weight ratio of phospholipid and Radix Ginseng dammarane aglycon is 1:500～1:20, and preferred proportion is 1:200～1:50.In the Radix Ginseng dammarane aglycon grinding suspension making, the amount of Radix Ginseng dammarane aglycon is 30～50%.
The time of grinding is 0.5～3 hour, preferably 1 hour.Particle size determination scattergram as shown in Figure 1.
In another embodiment, use Radix Ginseng dammarane aglycon grinding suspension, by Radix Ginseng dammarane aglycone preparation downstream process, prepare the pharmaceutical preparation of Radix Ginseng dammarane aglycon.
Add suitable adjuvant to make related preparations the Radix Ginseng dammarane aglycon grinding suspension of above-mentioned preparation, as quick-release capsules or quick-release tablet.
Radix Ginseng dammarane aglycon quick-release capsules:
(a) Radix Ginseng dammarane aglycon suspension is diluted to debita spissitudo, then that the uniform lamination of lapping liquid is surperficial to Blank Pellets, Blank Pellets can be microcrystalline Cellulose ball, sucrose ball or starch ball.Micropill after lamination is dry 12h at 40 ℃;
(b) micropill is filled with to suitable capsule shells.
Radix Ginseng dammarane aglycon fast-release tablet:
(a) Radix Ginseng dammarane aglycon suspension adds suitable excipient to be prepared into quick-release tablet.The conventional excipients with rapid release performance comprises: filler, as starch, dextrin, lactose, mannitol and microcrystalline Cellulose; Disintegrating agent, as cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and sodium lauryl sulphate; Lubricant, as magnesium stearate, Pulvis Talci;
(b) Radix Ginseng dammarane aglycon sheet preparation process:
I, granule preparation: Radix Ginseng dammarane aglycon suspension adds one or more filleies, also adds a certain amount of SDS to be prepared into 24 order～48 order granules, 40 ℃ of dry 12h, 32 order granulate simultaneously;
After II, whole complete grain, add one or more disintegrating agents and antiplastering aid, mix rear tabletting, compacting has the tablet of suitable hardness, has rapid release characteristic;
(c) in Radix Ginseng dammarane aglycon fast-release tablet preparation process, Radix Ginseng dammarane aglycon granule and suitable adjuvant compacting is in blocks, can make the good quick-release tablet of disintegrate.In experiment, find that Radix Ginseng dammarane aglycon dissolution in 45min can reach more than 65%.
Embodiment 1
Get 100mg Radix Ginseng dammarane aglycon test sample powder, pour into capsule, the aqueous solution 500ml of take containing 0.1% sodium lauryl sulphate is solvent, rotating speed is per minute 75 to turn, and gets solution suitable during through 45 minutes, filters, it is appropriate that precision measures filtrate, as need testing solution; Separately, it is appropriate that precision measures Radix Ginseng dammarane aglycon reference substance, uses same dissolution with solvents and make the solution suitable with need testing solution concentration, in contrast product solution; Get above-mentioned two kinds of solution, inject high performance liquid chromatograph, at the wavelength place of 203nm, measure respectively peak area, calculate stripping quantity.Recording 45min dissolution is 28%.
The dissolution determination condition adopting in the present invention is all with embodiment 1.
Embodiment 2
The preparation of Radix Ginseng dammarane aglycon grinding suspension:
Radix Ginseng dammarane aglycon 1200g
HPMC aqueous solution 600g containing phospholipid;
Preparation process: take Radix Ginseng dammarane aglycon 1200g, be divided into 3 parts, every part of 400g, getting respectively concentration is 3% again, 5% and 8%(adopt variable concentrations be for confirm variable concentrations HPMC on the peptizaiton of medicine with and the binding agent effect that produces in tabletting process on the impact discharging) HPMC aqueous solution 600ml, taking 4g phospholipid is dispersed in HPMC aqueous solution, every part of 400g Radix Ginseng dammarane aglycon is divided to feed intake for four times adds respectively the 600g of above-mentioned three kinds of concentration containing in the HPMC aqueous solution of phospholipid, after mix homogeneously, be positioned in grinding cup, at 1500 rmin
-1in the basket-type grinder running up, grind 1h.
Radix Ginseng dammarane aglycon after above-mentioned grinding under the microscope particle diameter be decreased to below 500nm, there is certain viscosity, with above-mentioned grinding suspension, prepare quick releasing formulation.
Embodiment 3
Radix Ginseng dammarane aglycon suspension 30g(is in Radix Ginseng dammarane aglycon)
Amylum pregelatinisatum 40g
Microcrystalline Cellulose 10g
Cross-linking sodium carboxymethyl cellulose 15g
Magnesium stearate 4g
Take respectively recipe quantity 3%, 5% and 8%HPMC-Radix Ginseng dammarane aglycon suspension, then add above-mentioned recipe quantity amylum pregelatinisatum, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, after making soft material, cross 40 mesh sieves granulations, the particle making is put into baking oven dry 12h at 40 ℃ of temperature.Dry completely after by 40 mesh sieve granulate for particle.Then press recipe quantity by after particle and residue auxiliary materials and mixing, tabletting, every agreement that contracts a film or TV play to an actor or actress is containing Radix Ginseng dammarane aglycon 100mg.Recording 45min dissolution is respectively: 50%, 60%, 62%.After making fast-release tablet, 45min discharges 45%, 54%, 50%.
Experimental result shows, when jointly grinding as hydrophilicity condiment and Radix Ginseng dammarane aglycon with 5%HPMC, the result of extraction of Radix Ginseng dammarane aglycon tablet is best, the hydrophilicity condiment solution that therefore the final 5%HPMC of determining grinds as Radix Ginseng dammarane aglycon in preparing the experiment of Radix Ginseng dammarane aglycon fast-release tablet.The grinding suspension of all the other all embodiment in the present invention below in Radix Ginseng dammarane aglycon fast-release tablet experiment is all that 5%HPMC is with the common grinding product of Radix Ginseng dammarane aglycon.
Embodiment 4
Radix Ginseng dammarane aglycon grinding suspension 30g(is in Radix Ginseng dammarane aglycon)
Microcrystalline Cellulose 35g
Carboxymethyl starch sodium 16.6g
Pulvis Talci 6.4g
Take recipe quantity Radix Ginseng dammarane aglycon lapping liquid, then add recipe quantity lactose, microcrystalline Cellulose, carboxymethyl starch sodium, make and cross 40 mesh sieves after soft material and granulate, the particle making is put into baking oven dry 12h at 40 ℃ of temperature.Dry completely after by 40 mesh sieve granulate for particle.Then press recipe quantity by after particle and residue auxiliary materials and mixing, tabletting, every agreement that contracts a film or TV play to an actor or actress is containing Radix Ginseng dammarane aglycon 100mg.
Stripping measurement result is: this granule 45min discharges 65%, and tablet 45min discharges 50%.
Embodiment 5
Radix Ginseng dammarane aglycon grinding suspension 30g(is in Radix Ginseng dammarane aglycon)
Lactose 50g
Microcrystalline Cellulose 25g
Carboxymethyl starch sodium 16.6g
Sodium lauryl sulphate 5g
Pulvis Talci 6.4g
Take recipe quantity Radix Ginseng dammarane aglycon lapping liquid, then add recipe quantity lactose, microcrystalline Cellulose, carboxymethyl starch sodium, sodium lauryl sulphate, make and cross 40 mesh sieves after soft material and granulate, the particle making is put into baking oven dry 12h at 40 ℃ of temperature.Dry completely after by 40 mesh sieve granulate for particle.Then press recipe quantity by after particle and residue auxiliary materials and mixing, tabletting, every agreement that contracts a film or TV play to an actor or actress is containing Radix Ginseng dammarane aglycon 100mg.
Stripping measurement result is: this granule discharges 68% at 45min, and tablet dissolution when 45min can reach 60%.
Embodiment 6
?radix Ginseng dammarane aglycon grinding suspension 30g(is in Radix Ginseng dammarane aglycon)
Lactose 50g
Microcrystalline Cellulose 25g
Carboxymethyl starch sodium 16.6g
Sodium lauryl sulphate 5g
Pulvis Talci 6.4g
Take recipe quantity lapping liquid, then add recipe quantity lactose, microcrystalline Cellulose, sodium lauryl sulphate and 10g carboxymethyl starch to receive, make and cross 40 mesh sieves after soft material and granulate, the particle making is put into baking oven dry 12h at 40 ℃ of temperature.Dry completely after by 40 mesh sieve granulate for particle.Then press recipe quantity by after particle and residue auxiliary materials and mixing, tabletting, every agreement that contracts a film or TV play to an actor or actress is containing Radix Ginseng dammarane aglycon 100mg.
Stripping measurement result is: this formula makes granule 45min stripping and discharges 70%, and Dissolution of Tablet reaches 66% when 45min.
Embodiment 7
Radix Ginseng dammarane aglycon grinding suspension 30g(is in Radix Ginseng dammarane aglycon)
MCC blank pill 30g
The concentration that recipe quantity Radix Ginseng dammarane aglycon grinding suspension is diluted to Radix Ginseng dammarane aglycon is about 5%, then that the uniform lamination of lapping liquid is surperficial to MCC Blank Pellets.Micropill after lamination is dry 12h at 40 ℃.Micropill is filled with to suitable capsule shells, and every capsules is approximately containing Radix Ginseng dammarane aglycon 100mg.
Recording 45min dissolution is 60%.
Embodiment 8
Radix Ginseng dammarane aglycon grinding suspension 30g(is in Radix Ginseng dammarane aglycon)
Sucrose blank pill 120g
The concentration that recipe quantity Radix Ginseng dammarane aglycon grinding suspension is diluted to Radix Ginseng dammarane aglycon is about 5%, then that the uniform lamination of lapping liquid is surperficial to sucrose Blank Pellets.Micropill after lamination is dry 12h at 40 ℃.Micropill is filled with to suitable capsule shells, and every capsules is approximately containing Radix Ginseng dammarane aglycon 100mg.
Recording 45min dissolution is 62%.
Embodiment 9
Bioavailability study:
Laboratory animal: beagle dog, male and female half and half.
Experimental agents: Radix Ginseng dammarane aglycon capsule, Radix Ginseng dammarane aglycon tablet, capsule is that Radix Ginseng dammarane aglycon crude drug powder is directly recorded, tablet is embodiment 6 method preparations.
Experimental technique: by 12 of beagle dogs, be divided at random 2 groups, 6 every group.Before administration, fasting is 12 hours, personal drinking-water.
First group: oral Radix Ginseng dammarane aglycon Capsules group, dosage is 2 of 100mg capsules; Second group: oral Radix Ginseng dammarane aglycon tablet group, dosage is 2,100mg tablet.After each treated animal administration, different time points venae subcutaneae inside dog forelimb about 0.5ml that takes a blood sample, is placed in the test tube of heparinization, and separated plasma, adopts superelevation phase liquid phase tandem mass spectrometry to measure.As a result, tablet protopanoxadiol t1/2 is 9.6h, and capsule protopanoxadiol t1/2 is 21.3h, and tablet Protopanaxatriol t1/2 is 9.8h, and capsule Protopanaxatriol t1/2 is 9.0h.Tablet is 1.60 to the relative bioavailability of the protopanoxadiol of capsule, and Protopanaxatriol's relative bioavailability is 1.35.
Claims (6)
1. dammarane's aglycon suspension, it is characterized in that, described dammarane's aglycon suspension comprises the component of following percentage by weight: dammarane's aglycon 30～50%, hydrophilicity condiment 3～8% and the phospholipid that is 1:50～1:200 with the weight ratio of described dammarane's aglycon, and other are water;
Described hydrophilicity condiment is selected from one or more in polyvinylpyrrolidone PVP, gelatin and xanthan gum;
Its preparation method comprises the steps:
(1) phospholipid is dispersed in hydrophilicity condiment aqueous solution, then adds dammarane's aglycon of first batch, under grinder, grind, milling time is 0.5～3 hour;
(2) add residue batch dammarane's aglycon, the operation of repeating step (1), the percentage by weight of final described dammarane's aglycon is 30～50%, the percentage by weight of hydrophilicity condiment is 3～8%, and the weight ratio of described phospholipid and described dammarane's aglycon is 1:50～1:200;
The particle diameter of described dammarane's aglycon is less than 500nm.
2. the preparation method of dammarane's aglycon suspension claimed in claim 1, is characterized in that, comprises the steps:
(1) phospholipid is dispersed in hydrophilicity condiment aqueous solution, then adds dammarane's aglycon of first batch, under grinder, grind, milling time is 0.5～3 hour;
(2) add dammarane's aglycon of remaining batch, the operation of repeating step (1), the percentage by weight of final described dammarane's aglycon is 30～50%, the percentage by weight of described hydrophilicity condiment is 3～8%, and the weight ratio of described phospholipid and described dammarane's aglycon is 1:50～1:200.
3. according to the preparation method of claim 2, it is characterized in that, the rotating speed of described grinder is 1200～1800rmin
-1.
4. the application of the arbitrary described dammarane's aglycon suspension of claims 1 to 3, is characterized in that, described dammarane's aglycon suspension lamination is made to tablet or capsule to the surface of blank pill, and described blank pill is microcrystalline Cellulose ball, sucrose ball or starch ball.
5. application according to claim 4, is characterized in that, described tablet or capsule also comprise excipient substance, and described excipient substance is filler, disintegrating agent and lubricant.
6. application according to claim 5, is characterized in that, described filler is selected from one or more in starch, dextrin, lactose, mannitol and microcrystalline Cellulose, and the percentage by weight that accounts for described tablet or capsule is 40～70%;
Described disintegrating agent is selected from one or more in cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and sodium lauryl sulphate, and the weight percent that accounts for described tablet or capsule is 10～20%;
Described lubricant is selected from one or more in magnesium stearate, Pulvis Talci, and the percentage by weight that accounts for described tablet or capsule is 3～7%.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1795868A (en) * | 2004-12-23 | 2006-07-05 | 中国科学院大连化学物理研究所 | Medication possessing activity of fighting against senium |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1795868A (en) * | 2004-12-23 | 2006-07-05 | 中国科学院大连化学物理研究所 | Medication possessing activity of fighting against senium |
Non-Patent Citations (4)
| Title |
|---|
| 中药活性成分磷脂复合物的研究进展;戈延茹等;《时珍国医国药》;20101231;第21卷(第8期);第2107－2109页 * |
| 壳聚糖磷脂复合物的制备;王学东等;《潍坊医学院学报》;20051231;第27卷(第3期);第170－172页 * |
| 戈延茹等.中药活性成分磷脂复合物的研究进展.《时珍国医国药》.2010,第21卷(第8期),第2107－2109页. |
| 王学东等.壳聚糖磷脂复合物的制备.《潍坊医学院学报》.2005,第27卷(第3期),第170－172页. |
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