CN105708847A - Preparing method and application of ginsenoside-multi-component jointly-loading targeting nanometer system - Google Patents
Preparing method and application of ginsenoside-multi-component jointly-loading targeting nanometer system Download PDFInfo
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Abstract
The invention discloses a preparing method of a ginsenoside-multi-component jointly-loading targeting nanometer system.The preparing method includes the steps that after egg yolk lecithin, cholesterol and polyethylene glycol-dipalmitoyl phosphatidyl choline are dissolved, warm water is slowly and dropwise added for stirring, and a lipid water solution is obtained; the multi-component active ingredients containing ginsenoside Rg3, ginsenoside Rh2 and ginsenoside Rb1 and a copolymer of polylactic acid-hydroxyacetic acid are dissolved to be slowly and dropwise added into the lipid water solution to be stirred to be even, a solvent is removed, and lipidosome nanometer particles are obtained; aptamer is dissolved to be modified to the surfaces of the lipidosome nanometer particles, and an even and opalescence-flooding nanometer system solution is obtained by filtering and sterilizing.According to the preparing method, the anti-tumor effect of medicine is improved with the nanocrystallization technology, joint transmission of a multi-component tumor tissue can be achieved in the mode that the three ginsenoside ingredients are jointly loaded to the nanometer system, and therefore the problems that the metabolic behaviors and the tumor-cell entering capacity of different ingredients are different are solved.
Description
Technical field
The present invention relates to, be specifically related to a kind of ginsenoside's multicomponent and carry the preparation method of targeted nano system altogether.
Background technology
Active ingredient of Chinese herbs has given play to more and more significant curative effect at anti-tumor aspect, at present active ingredient of Chinese herbs still suffers from some problems in antitumor is applied, the most most of cancer therapy drug poorly water-solubles, difficult absorb, the half-life is short, delivery efficiency is low, free drug targeting difference etc..Anti-tumor Chinese herbal preparation needs the realistic problem of solution badly: on the premise of ensureing preparation security, improves the delivery of Effective Component of Chinese Medicine, improves the tumor-targeting of effective ingredient；For particular type tumor appropriate design dosage form, explore and enrich the new route of administration of anti-tumor Chinese medicine.
In recent years, the cross-application of nanoscale medicine delivery system and novel biomaterial is that the effectively transmission of cancer therapy drug brings new hope, the internal safety of medicine can be significantly improved by nano-carrier bag medicine carrying thing, its " nano-scale " can strengthen intestinal absorption, promotes that medicine is in the accumulation of tumor tissues；Cellular uptake and tumor-targeting ability can also be improved by the modification of surface specific function group.Therefore, in nanometer formulation technology is raising anti-tumor Chinese medicine body, safety and delivery efficiency, abundant pharmaceutical administration provide feasible approach.
But Traditional Chinese Medicine Anti antitumor moiety is different from chemotherapeutics, its antineoplastic " singles solely struggle against " ability is the most all weaker than chemical medicine, but its effect has Mutiple Targets, multi-stratification, being suitable for multicomponent synergism, therefore exploitation Chinese medicine multicomponent delivery system becomes one of emphasis of current antitumor research.But owing to different active ingredient of Chinese herbs exist larger difference at aspects such as physicochemical property, biological penetration, distribution in vivo, effective doses, it is difficult to ensure that when each composition transmits altogether in free mode, can assemble with constant ratio at lesions position, thus it is difficult to optimal synergistic antitumor effect, thus traditional Traditional Chinese Medicine Anti antineoplastic agents is based substantially on composition self destiny in vivo and dominates clinical efficacy, its therapeutic effect and safety are the most all passive, uncontrollable.
Ginsenoside is the general name of multiple saponin component in Radix Ginseng, the most separated and identify more than 60 kind, wherein the strongest with composition antitumor actions such as Rh2, Rg3, Rb1, its antitumor mechanism shows as suppressing tumor growth and tumor angiogenesis, reverse multiple drug resistance of tumor, the expression affecting tumor signal transduction related gene and enhancing patient's immunocompetence, have efficacy enhancing and toxicity reducing effect etc. to chemotherapy.Study the multiple nano-carriers such as employing nano-micelle, nano-emulsion, solid lipid nanoparticle, Nano microsphere at present and single ginsenoside's composition has been carried out bag load；Research is additionally had to use micelle to carry out common load, for antitumor or other aspects ginsenoside Rg3, tri-kinds of compositions of Rb1, Rh2.But compared with lipid nanoparticle, during polymer micelle storage and to enter body circulation rear stability relatively poor, its drug carrying ability is limited simultaneously, therefore at present clinical antineoplastic nanometer formulation still based on lipid nanoparticle.The disclosedest Chinese patent CN
103271891A discloses a kind of ginsenoside nano-micelle and preparation method thereof, application and pharmaceutical composition, this patent have employed ginsenoside's effective ingredient carry altogether with nanometer polymer micelle, solve the problem that fat-soluble medicine is insoluble in water, overcome the existing defect that polymer micelle medicine carrying ability is undesirable, bio-compatibility is poor, yet with polymer micelle self and the defective workmanship of this patent, the most do not solve the active targeting problem of ginsenoside, and tumor tissue cell's picked-up ability is inadequate, thus cause the drug level of target tissue low.
Additionally, the tumor tissues efficiency of transmission of passive targeted preparation is limited, exploitation has the active targeting nanosystems of good cancer target effect and has more application prospect.But yet there are no with good grounds ginsenoside's composition antitumor action design gained active targeting nanometer system, the novel delivery system that ginsenoside's multicomponent carries altogether is needed badly perfect.
Summary of the invention
It is an object of the invention to provide a kind of ginsenoside's multicomponent and carry the preparation method of targeted nano system altogether, poor biocompatibility in prior art, stability can be solved relatively low, the defect that tumor tissue cell's active constituents of medicine distribution is few, can obtain water solublity height, absorbability is good, stability is high, have active targeting, the effect that active component can be assembled at tumor tissues.
For reaching above-mentioned purpose, one embodiment of the present of invention provides a kind of ginsenoside's multicomponent and carries the preparation method of targeted nano system altogether, comprise the following steps:
Step 1, Ovum Gallus domesticus Flavus lecithin, cholesterol and Polyethylene Glycol-dipalmitoyl phosphatidyl choline are dissolved after be slowly added dropwise warm water stirring, obtain lipid aqueous solution；
Step 2, the multicomponent effective ingredient comprising ginsenoside Rg3, ginsenoside Rh2 and ginsenoside Rb1 and Poly(D,L-lactide-co-glycolide are dissolved after be slowly added dropwise and stir to lipid aqueous solution and remove solvent, obtain liposome nano granule；
Step 3, aptamer is dissolved after modify in liposome nano granule surface, eventually pass filtration, sterilizing obtains the nanometer system solution of uniform general opalescence.
Prioritization scheme as the present invention, Ovum Gallus domesticus Flavus lecithin, cholesterol and Polyethylene Glycol-dipalmitoyl phosphatidyl choline in step 1 are dissolved in dehydrated alcohol, and in described step 2, ginsenoside's multicomponent effective ingredient and Poly(D,L-lactide-co-glycolide are dissolved in acetonitrile.
As the prioritization scheme of the present invention, in step 2, Radix Ginseng multicomponent effective ingredient is ultrasonically treated after dissolving with Poly(D,L-lactide-co-glycolide and drops in lipid aqueous solution again.
As the prioritization scheme of the present invention, in step 2, multicomponent effective ingredient is slowly added dropwise after dissolving with Poly(D,L-lactide-co-glycolide and stirs under the conditions of ice bath and ultrasonic Treatment to lipid aqueous solution.
As the prioritization scheme of the present invention, step 3 amplifying nucleic acid aptamers is aptamers AS1411.
As the prioritization scheme of the present invention, step 3 amplifying nucleic acid aptamers uses phosphate buffer solution to dissolve.
As the prioritization scheme of the present invention, the filter membrane using aperture to be 0.45 μm in step 3 is removed unentrapped medicine, is used the filter membrane of 0.2 μm to filter pathogen.
As the prioritization scheme of the present invention, in multicomponent effective ingredient, the content of ginsenoside Rg3 is 10% ~ 25%, and the content of ginsenoside Rh2 is 10% ~ 15%, and the content of ginsenoside Rb1 is 10% ~ 15%, and the total amount of Rg3, Rh2 and Rb1 is more than or equal to 40%.
As the prioritization scheme of the present invention, containing Ovum Gallus domesticus Flavus lecithin 1% ~ 5%, cholesterol 1% ~ 5%, Polyethylene Glycol-dipalmitoyl phosphatidyl choline 0.5% ~ 5%, Poly(D,L-lactide-co-glycolide 10% ~ 35%, aptamer 0.5% ~ 2% in nanometer system solution.
Additionally, the present invention has also opened carries the application in preparing antitumor drug of the targeted nano system by what said method obtained altogether containing ginsenoside's multicomponent.
Additionally, the corresponding abbreviation synopsis of the name of material of the present invention is as follows:
| English abbreviation | Chinese |
| PEG-DPPC | Polyethylene Glycol-dipalmitoyl phosphatidyl choline |
| PLGA | Poly(D,L-lactide-co-glycolide |
| PBS | Phosphate buffer |
In sum, the invention have the advantages that
The present invention increases the antitumor action of medicine by nanorize, three-type-person joins saponin constituent and is loaded in altogether in nanosystems and can realize multicomponent tumor tissues and transmit altogether, thus overcome the problem that heterogeneity metabolism behavior is different and entrance tumor cell ability is different.The present invention uses lipid polymer nanometer system simultaneously, its good biocompatibility, low cost, it is easy to industrialized production, can overcome existing cosolvent or other pass prescription formula exist safety issue, significant.
The present invention uses aptamers AS1411 modify in nanoparticle surface, with the p120 of targets neoplastic cells surface expression as receptor, such that it is able to tumor cell high specific, the combination of high-affinity.And carrier system is without organic solvent and the solubilizing agent of toxic side effect altogether for the multicomponent that the present invention provides, and therefore without anaphylaxis, side effect is little.
The content of the nanoparticle active component that the present invention provides is higher; meet the high concentration needed for clinical drug effect; this system can also change saponin distribution in human body by EPR effect simultaneously; improve the bioavailability of medicine; ginsenoside can be made to be concentrated on tumor locus in vivo simultaneously, improve the tumor-inhibiting action of this compound.
Accompanying drawing explanation
Fig. 1 is the schematic diagram of the present invention；
Fig. 2 is the HPLC mensuration figure that three-type-person joins saponin；
Fig. 3 is the mean diameter DLS mensuration figure of ginsenoside's lipid polymer nanoparticle；
Fig. 4 is the potential measurement figure of ginsenoside's lipid polymer nanoparticle；
Fig. 5 is the transmission electron microscope picture of ginsenoside's lipid polymer nanoparticle；
Fig. 6 is the vitro drug release figure of ginsenoside's lipid polymer nanoparticle.
Detailed description of the invention
Embodiment 1
5mg Ovum Gallus domesticus Flavus lecithin, 5mg cholesterol being dissolved in 2mL dehydrated alcohol with 2.5mg PEG-DPPC material, be slowly added dropwise in the water of 60 ° of C of 20mL, continuously stirred 5min obtains lipid aqueous solution.15mg PLGA material, 10mg ginsenoside Rg3,5mg ginsenoside Rh2 and 5mg ginsenoside Rb1 are dissolved in acetonitrile, it is slowly dropped into after ultrasonic Treatment 1min in above-mentioned lipid aqueous solution, supersound process 20min under ice bath, the most continuously stirred 30min, use Rotary Evaporators decompression to remove residual organic solvents, add 0.1uM
Accounting aptamers AS1411, continue stirring 30min, remove unentrapped medicine by the filter membrane of 0.45 μm, after 0.2 μm filter membrane sterilizing, obtain uniform general opalescence nanometer solution, be prepared as common carrying three-type-person and joining the lipid nanoparticle solution of saponin constituent.
Embodiment 2
5mg Ovum Gallus domesticus Flavus lecithin, 5mg cholesterol being dissolved in 2mL dehydrated alcohol with 2.5mg PEG-DSPE material, be slowly added dropwise in the water of 60 ° of C of 20mL, continuously stirred 5min obtains lipid aqueous solution.15mg PLGA material, 10mg ginsenoside Rg3,5mg ginsenoside Rh2 and 5mg ginsenoside Rb1 are dissolved in acetonitrile, it is slowly dropped into after ultrasonic Treatment 1min in above-mentioned lipid aqueous solution, supersound process 20min under ice bath, the most continuously stirred 30min, use Rotary Evaporators decompression to remove residual organic solvents, add 0.1uM
Accounting aptamers AS1411, continue stirring 30min, remove unentrapped medicine by the filter membrane of 0.45 μm, after 0.2 μm filter membrane sterilizing, obtain uniform general opalescence nanometer solution, be prepared as common carrying three-type-person and joining the lipid nanoparticle solution of saponin constituent.
Embodiment 3
5mg Ovum Gallus domesticus Flavus lecithin, 5mg cholesterol being dissolved in 2mL dehydrated alcohol with 2.5mg DSPE-PEG-COOH material, be slowly added dropwise in the water of 60 ° of C of 20mL, continuously stirred 5min obtains lipid aqueous solution.15mg PLGA material, 10mg ginsenoside Rg3,5mg ginsenoside Rh2 and 5mg ginsenoside Rb1 are dissolved in acetonitrile, it is slowly dropped into after ultrasonic Treatment 1min in above-mentioned lipid aqueous solution, supersound process 20min under ice bath, the most continuously stirred 30min, use Rotary Evaporators decompression to remove residual organic solvents, add 0.1uM
Accounting aptamers AS1411, continue stirring 30min, remove unentrapped medicine by the filter membrane of 0.45 μm, after 0.2 μm filter membrane sterilizing, obtain uniform general opalescence nanometer solution, be prepared as common carrying three-type-person and joining the lipid nanoparticle solution of saponin constituent.
Embodiment 4
5mg Ovum Gallus domesticus Flavus lecithin, 5mg cholesterol being dissolved in 2mL dehydrated alcohol with 2.5mgDSPE-PEG-Folate material, be slowly added dropwise in the water of 60 ° of C of 20mL, continuously stirred 5min obtains lipid aqueous solution.15mg PLGA material, 10mg ginsenoside Rg3,5mg ginsenoside Rh2 and 5mg ginsenoside Rb1 are dissolved in acetonitrile, it is slowly dropped into after ultrasonic Treatment 1min in above-mentioned lipid aqueous solution, supersound process 20min under ice bath, the most continuously stirred 30min, use Rotary Evaporators decompression to remove residual organic solvents, add 0.1uM
Accounting aptamers AS1411, continue stirring 30min, remove unentrapped medicine by the filter membrane of 0.45 μm, after 0.2 μm filter membrane sterilizing, obtain uniform general opalescence nanometer solution, be prepared as common carrying three-type-person and joining the lipid nanoparticle solution of saponin constituent.
Embodiment 5
5mg Ovum Gallus domesticus Flavus lecithin, 5mg cholesterol being dissolved in 2mL dehydrated alcohol with 2.5mg PEG-DPPC material, be slowly added dropwise in the water of 60 ° of C of 20mL, continuously stirred 5min obtains lipid aqueous solution.15mg PLGA material, 10mg ginsenoside Rg3,5mg ginsenoside Rh2 and 5mg ginsenoside Rb1 are dissolved in acetonitrile, it is slowly dropped into after ultrasonic Treatment 1min in above-mentioned lipid aqueous solution, supersound process 20min under ice bath, the most continuously stirred 30min, Rotary Evaporators decompression is used to remove residual organic solvents, unentrapped medicine is removed by the filter membrane of 0.45 μm, after 0.2 μm filter membrane sterilizing, obtain uniform general opalescence nanometer solution, be prepared as common load three-type-person and join the lipid nanoparticle solution of saponin constituent.
Embodiment 6
5mg Ovum Gallus domesticus Flavus lecithin, 5mg cholesterol being dissolved in 2mL dehydrated alcohol with 2.5mg PEG-DSPE material, be slowly added dropwise in the water of 60 ° of C of 20mL, continuously stirred 5min obtains lipid aqueous solution.15mg PLGA material, 10mg ginsenoside Rg3,5mg ginsenoside Rh2 and 5mg ginsenoside Rb1 are dissolved in acetonitrile, it is slowly dropped into after ultrasonic Treatment 1min in above-mentioned lipid aqueous solution, supersound process 20min under ice bath, the most continuously stirred 30min, Rotary Evaporators decompression is used to remove residual organic solvents, unentrapped medicine is removed by the filter membrane of 0.45 μm, after 0.2 μm filter membrane sterilizing, obtain uniform general opalescence nanometer solution, be prepared as common load three-type-person and join the lipid nanoparticle solution of saponin constituent.
Embodiment 7
5mg Ovum Gallus domesticus Flavus lecithin, 5mg cholesterol being dissolved in 2mL dehydrated alcohol with 2.5mg DSPE-PEG-COOH material, be slowly added dropwise in the water of 60 ° of C of 20mL, continuously stirred 5min obtains lipid aqueous solution.15mg PLGA material, 10mg ginsenoside Rg3,5mg ginsenoside Rh2 and 5mg ginsenoside Rb1 are dissolved in acetonitrile, it is slowly dropped into after ultrasonic Treatment 1min in above-mentioned lipid aqueous solution, supersound process 20min under ice bath, the most continuously stirred 30min, Rotary Evaporators decompression is used to remove residual organic solvents, unentrapped medicine is removed by the filter membrane of 0.45 μm, after 0.2 μm filter membrane sterilizing, obtain uniform general opalescence nanometer solution, be prepared as common load three-type-person and join the lipid nanoparticle solution of saponin constituent.
Embodiment 8
5mg Ovum Gallus domesticus Flavus lecithin, 5mg cholesterol being dissolved in 2mL dehydrated alcohol with 2.5mgDSPE-PEG-Folate material, be slowly added dropwise in the water of 60 ° of C of 20mL, continuously stirred 5min obtains lipid aqueous solution.15mg PLGA material, 10mg ginsenoside Rg3,5mg ginsenoside Rh2 and 5mg ginsenoside Rb1 are dissolved in acetonitrile, it is slowly dropped into after ultrasonic Treatment 1min in above-mentioned lipid aqueous solution, supersound process 20min under ice bath, the most continuously stirred 30min, Rotary Evaporators decompression is used to remove residual organic solvents, unentrapped medicine is removed by the filter membrane of 0.45 μm, after 0.2 μm filter membrane sterilizing, obtain uniform general opalescence nanometer solution, be prepared as common load three-type-person and join the lipid nanoparticle solution of saponin constituent.
Experimental example: the rat with liver tumor is taken the Nano medication in embodiment 1 ~ embodiment 8, and detect the drug level contained in rat liver tissue in medication 6h ~ 12h, and then judge that medicine is in the aggregation extent of liver organization and persistent period.
Wherein, nanometer system in embodiment 1 ~ embodiment 4 has accessed aptamer, and the drug level at liver organization is significantly greater than embodiment 5 ~ embodiment 8, illustrates that aptamer can significantly improve the active targeting ability of medicine, higher drug level, beneficially therapeutic effect is obtained at affected area.Distinguish less additionally, the liver organization of embodiment 5 ~ embodiment 8 opens drug level, the most do not possess significant difference；Embodiment 1 is compared with embodiment 2 ~ embodiment 4, its aptamer remaining system compared with the common carrier system of PEG-DPPC is more stable, nanometer system containing PEG-DPPC copolymer is compared other copolymer nano systems and is had the more preferable compatibility, the liver organization drug level of embodiment 1 is the most significantly higher compared with embodiment 2 ~ 4, and there is significant difference, the PEG-DPPC of the present embodiment can promote to adjust the efficiency that aptamers is combined with receptor, improves the concentration of effective active composition in focus.
In order to prove the implementation result of the present invention, the existing method of the nanometer system prepared according to method described in embodiment 1 use is measured, concrete mensuration mode and result such as test example 1 ~ test example 3.
Test example 1: three-type-person joins the assay of saponin
Using Waters e2695 HPLC-UV method to measure three-type-person simultaneously and join saponin content, its chromatographic condition is as follows: chromatographic column: Waters C18 post (250mm × 4.6mm, 5 μm)；Column temperature: 25 DEG C；Detection wavelength: 203nm；Flowing phase: water (A) and acetonitrile (B)；Flow velocity: 1.0mL/min；Condition of gradient elution is shown in Table 1.Measurement result is as shown in Figure 2.
Table 1 HPLC method measures three-type-person simultaneously and joins the condition of gradient elution of saponin constituent
| Time/min | Water (A) % | Acetonitrile (B) % |
| 0 | 75 | 25 |
| 4 | 60 | 40 |
| 10 | 35 | 65 |
| 13 | 30 | 70 |
Test example 2: the physics and chemistry evaluation of ginsenoside's nanoparticle
(1) outward appearance and stability: be placed in centrifuge tube by ginsenoside's nanoparticle solution of preparation, seals, and is respectively placed in 60 ° of C constant water bath box, after 4 ° of C preserve one week, recovers to room temperature.
(2) morphologic observation: take the prepared ginsenoside's nanoparticle solution of optimization formulation technique appropriate, distilled water diluting to 1mg/mL, use transmission electron microscope observing particle shape after phosphotungstic acid negative staining.
(3) particle diameter and distribution: take 1mg/mL ginsenoside's nanoparticle solution, uses Malvern laser particle analyzer to measure particle diameter distribution and Zeta potential.
(4) envelop rate measures with drug loading: takes the nanoparticle solution before and after 0.45 μm filters respectively, adds 3 times amount methanol, ultrasonic emulsion breaking, and vortex 1min, centrifugal 10min under the rotating speed of 13000r/min, takes supernatant, sample introduction, and HPLC method measures medicament contg.Nano medication concentration × 100% before Nano medication concentration/filtration after envelop rate=filtration；Nano medication concentration/(Nano medication concentration+material concentration before filtering) × 100% after drug loading=filtration.The measurement result of test example 2 is as shown in Fig. 3 ~ Fig. 5, and in ginsenoside's nanoparticle, ginsenoside Rg3, the envelop rate of Rh2 and Rb1 are respectively 91.4%, 86.5% and 94.3%.
Test example 3: the release in vitro of ginsenoside's nanoparticle
The release behaviour in vitro of bag medicine carrying thing in nanoparticle is measured by dialysis.The bag filter of molecular retention amount 3500 is boiled and is placed in distilled water soaking more than 24h.Take 2mL nanoparticle solution to be placed in bag filter, two ends are tightened, it is placed in 37 DEG C of 40mL PBS liquid containing 0.1% tween, and be stirred continuously with 300r/min magnetic stirring apparatus, respectively at 0.25,0.5,1,2,4,8,12,24,48,72h draw bag filter external solution 1mL, supplement the reception liquid of equivalent every time.HPLC method measures different time points and receives liquid drug concentration, calculates the content of medicine, calculates to obtain cumulative release percent, and measurement result is as shown in Figure 6.
Claims (10)
1. ginsenoside's multicomponent carries a preparation method for targeted nano system altogether, comprises the following steps:
Step 1, Ovum Gallus domesticus Flavus lecithin, cholesterol and Polyethylene Glycol-dipalmitoyl phosphatidyl choline are dissolved after slow
Slow dropping warm water stirring, obtains lipid aqueous solution；
Step 2, the multicomponent comprising ginsenoside Rg3, ginsenoside Rh2 and ginsenoside Rb1 is had
Effect composition is slowly added dropwise after dissolving with Poly(D,L-lactide-co-glycolide and stirs to lipid aqueous solution and go
Except solvent, obtain liposome nano granule；
Step 3, by aptamer dissolve after modify in liposome nano granule surface, eventually pass filtration, go out
Bacterium obtains the nanometer system solution of uniform general opalescence.
2. the method for claim 1, it is characterised in that: Ovum Gallus domesticus Flavus lecithin in described step 1,
Cholesterol and Polyethylene Glycol-dipalmitoyl phosphatidyl choline are dissolved in dehydrated alcohol, Radix Ginseng in described step 2
Saponin multicomponent effective ingredient and Poly(D,L-lactide-co-glycolide are dissolved in acetonitrile.
3. the method for claim 1, it is characterised in that: in described step 2, Radix Ginseng multicomponent is effective
Composition is ultrasonically treated after dissolving with Poly(D,L-lactide-co-glycolide and drops in lipid aqueous solution again.
4. the method for claim 1, it is characterised in that: multicomponent effective ingredient in described step 2
It is slowly added dropwise to lipid aqueous solution in ice bath and ultrasonic Treatment after dissolving with Poly(D,L-lactide-co-glycolide
Under the conditions of stir.
5. the method for claim 1, it is characterised in that: described step 3 amplifying nucleic acid aptamers is suitable
Part AS1411.
6. the method for claim 1, it is characterised in that: described step 3 amplifying nucleic acid aptamers uses
Phosphate buffer solution dissolves.
7. the method for claim 1, it is characterised in that: using aperture in described step 3 is 0.45
Unentrapped medicine removed by the filter membrane of μm, uses the filter membrane of 0.2 μm to filter pathogen.
8. the method for claim 1, it is characterised in that: Radix Ginseng soap in described multicomponent effective ingredient
The content of glycosides Rg3 is 10%～25%, and the content of ginsenoside Rh2 is 10%～15%, ginsenoside Rb1
Content be 10%～15%, and the total amount of Rg3, Rh2 and Rb1 is more than or equal to 40%.
9. the method for claim 1, it is characterised in that: containing egg yolk in described nanometer system solution
Lecithin 1%～5%, cholesterol 1%～5%, Polyethylene Glycol-dipalmitoyl phosphatidyl choline 0.5%～5%, poly-
Poly lactic coglycolic acid 10%～35%, aptamer 0.5%～2%.
10. what method described in claim 1～9 obtained carries targeted nano body altogether containing ginsenoside's multicomponent
Tie up to the application preparing in antitumor drug.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109248170A (en) * | 2017-07-13 | 2019-01-22 | 华东理工大学 | Target saponins compound and its application of PD-1 |
| CN110121346A (en) * | 2016-08-16 | 2019-08-13 | 詹森药业有限公司 | Neurosteroid composition and its application method |
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| CN110121346A (en) * | 2016-08-16 | 2019-08-13 | 詹森药业有限公司 | Neurosteroid composition and its application method |
| US10925912B2 (en) * | 2017-02-22 | 2021-02-23 | Jiangsu Province Institute of Traditional Chinese Medicine | Preparation and application of ginseng derived membranous microparticles |
| CN109248170A (en) * | 2017-07-13 | 2019-01-22 | 华东理工大学 | Target saponins compound and its application of PD-1 |
| CN109248170B (en) * | 2017-07-13 | 2023-10-03 | 华东理工大学 | PD-1 targeted saponin compound and application thereof |
| CN110269848A (en) * | 2019-07-05 | 2019-09-24 | 重庆医科大学 | A kind of targeting multifunctional nano grain and preparation method thereof for tumour cell |
| CN110551727A (en) * | 2019-09-02 | 2019-12-10 | 蚌埠医学院 | Ginsenoside aptamer and screening method and application thereof |
| CN111729087A (en) * | 2020-07-24 | 2020-10-02 | 成都大学 | Lipid modifier of selective beta 2 receptor agonist and preparation method and application thereof |
| CN114632072A (en) * | 2022-04-07 | 2022-06-17 | 陕西巨子生物技术有限公司 | Preparation and application of ginsenoside Rg5 lipid nanoparticle sustained release preparation |
| CN114632072B (en) * | 2022-04-07 | 2023-08-18 | 陕西巨子生物技术有限公司 | Preparation and application of ginsenoside Rg5 lipid nanoparticle sustained release preparation |
| CN115040494A (en) * | 2022-06-01 | 2022-09-13 | 南京中医药大学 | Ginsenoside-modified multifunctional nano vesicle loaded with multi-component compound and preparation method and application thereof |
| CN115040494B (en) * | 2022-06-01 | 2023-09-12 | 南京中医药大学 | Multifunctional nano vesicle of ginsenoside-modified co-carried multielement complex, and preparation method and application thereof |
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