CN105708801A - Preparation method and application of 20 (R)-ginsenoside Rg3/soya bean lecithin/cholesterol/folic acid lipidosome medicine - Google Patents
Preparation method and application of 20 (R)-ginsenoside Rg3/soya bean lecithin/cholesterol/folic acid lipidosome medicine Download PDFInfo
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Abstract
The invention relates to a preparation method and application of a 20 (R)-ginsenoside Rg3/soya bean lecithin/cholesterol/folic acid lipidosome medicine and belongs to the field of medicine health care products.By optimizing the ratio of soya bean lecithin, cholesterol and an encapsulation medicine to obtain 20 (R)-ginsenoside Rg3 lipidosome, the grain diameters of the 20 (R)-ginsenoside Rg3 lipidosome are reduced, and meanwhile the stability of the lipidosome medicine is enhanced; folic acid is used for conducting target modification on the encapsulated 20 (R)-ginsenoside Rg3 medicine lipidosome, and then target medicine delivery of cancer cells is achieved.Experimental results show that the encapsulation rate of the 20 (R)-ginsenoside Rg3 lipidosome can be up to 90% or above.The preparation method of the composite lipidosome medicine is simple and efficient.The prepared composite lipidosome is low in cytotoxicity, has the slow release feature and is capable of prolonging the curative effect, safe, efficient and high in targeting, good evaluating effects are obtained in physical representation and extracorporeal biological study, and a new approach is provided for research and development of anti-cancer medicines.
Description
Technical field
The present invention relates to a kind of 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament preparation method and application, belong to drugs and health care products field.
Background technology
Ginsenoside Rg3 (ginsenosides Rg3) is protopanaxadiol-type's tetracyclic triterpene saponin, and molecular formula is C42H72O13, relative molecular mass is 784.30, entitled 20 (R)-dammarane enediol-3-O-β-D-glucopyanosyl base (l-2)-β-D-glucopyanosyls of chemistry.Ginsenoside Rg3 mainly has 2 kinds of common configuration, 20 (R)-Propanaxadiol and 20 (S)-Propanaxadiol, and wherein 20 (R)-Propanaxadiol is Preferred conformations.20 (R)-ginsenoside Rg3s (20 (R)-ginsenosides Rg3) are first Chinese medicine monomer PTS of China, it it is one of effective ingredient playing antitumor action in ginsenoside, tumor neogenetic blood vessels can be effectively suppressed to increase, and then the growth transfer etc. of suppression tumor, the cancers such as carcinoma of prostate, pulmonary carcinoma, gastric cancer, hepatocarcinoma are had preferable therapeutic effect.Being used alone the shortcoming of Rg3 is its water solublity and fat-soluble the lowest, and therefore, bioavailability is relatively low.
Liposome is as the pharmaceutical carrier history of existing more than 30 year, soybean lecithin is as a kind of natural edible material avirulence, applicable body absorption and degraded, it is prepared as natural grease plastid with a certain proportion of cholesterol, for encapsulating 20 (R)-ginsenoside Rg3 medicines, drug bioavailability can be improved, extend the advantages such as drug treating time.
At present, the targeted cells of antitumor drug delivers and receives significant attention, and the experimental results shows, folacin receptor activity and quantity on most tumors cell surface are significantly higher than normally cell, and folic acid (folic acid, FA) has high affinity to folacin receptor.Therefore can be by liposome medicament and FA coupling, it is delivered in these tumor cells through folacin receptor mediated targeted, and FA has many unique advantages as targeted molecular, as little in relative molecular mass, non-immunogenicity, cheap and easy to get, good stability, targeting have wide range of applications.FA coupling liposome can effectively realize the targeted delivery of medicine as drug administration carrier, and the local improving medicine preserves concentration, strengthens the lethality to tumor cell, reduces Normocellular toxic and side effects etc..
Summary of the invention
For solving the deficiencies in the prior art, it is an object of the invention to provide a kind of 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament preparation method and application.The complex liposome medicine of the present invention, adjunct ingredient safety non-toxic, there is targeting, the tumor cell uptake rate to medicine can be increased, be effectively improved the bioavailability of 20 (R)-ginsenoside Rg3s.
Inventive concept is: the present invention is that main material is aided with cholesterol and prepares liposome with 20 (R)-ginsenoside Rg3s, native soy lecithin, use thin film dispersion ultrasonic method to realize effective encapsulating of 20 (R)-ginsenoside Rg3s, then be prepared as target liposomes medicine with folic acid encapsulating modification.
It is an object of the invention to be achieved through the following technical solutions: the preparation method of a kind of 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament, comprise the following steps:
(1) being dissolved in chloroform by soybean lecithin, add cholesterol, concussion makes it be sufficiently mixed uniformly, dries up the uniform thin film of formation with nitrogen stream, prepares liposome in placement vacuum drying oven overnight；
(2) it is first dissolved in 20 (R)-ginsenoside Rg3s in advance in dehydrated alcohol being configured to 20 (R)-ginsenoside Rg3 solution, in liposome, add 20 (R)-ginsenoside Rg3 solution and distilled water soaks, sonic oscillation makes Film Fractionation to clarification repeatedly, prepares encapsulating 20 (R)-ginsenoside Rg3 liposome；
(3) add folic acid solution and be combined 20 (R)-ginsenoside Rg3 liposomees, sonic oscillation is to clarification at normal temperatures, prepares 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament of folate-targeted sex modification.
Further, the soybean lecithin described in step (1) and cholesterol mol ratio are 1:1～6:1, preferably 3:1.
Further, the mass ratio of step (2) empty liposome and 20 (R)-ginsenoside Rg3s is 5:1～15:1, preferably 10:1.
Further, in step (2), 20 (R)-ginsenoside Rg3 solution concentrations are 2mg/mL.
Further, in step (2), 20 (R)-ginsenoside Rg3 solution and distilled water volume ratio are 2:8.
Further, final concentration of 10～40 μ g/mL of described step (3) folic acid, preferably 20 μ g/mL.
Further, in step (2) at 45～55 DEG C repeatedly sonic oscillation make Film Fractionation to clarification.
The present invention is also claimed and is prepared 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament by said method.
The 3rd purpose of the present invention is the application above-mentioned 20 (Rs)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament being claimed in anticancer, antitumor drug.
The present invention provide a kind of new while load medicine and the compound targeting liposome medicament of compound folic acid, the natural grease plastid constructing imitative membrane structure that the native soy lecithin that uses in the complex liposome component of the present invention is fabulous.The present invention obtains 20 (R)-ginsenoside Rg3 liposomees by the proportioning optimizing soybean lecithin and cholesterol and entrapped drug, reduces the particle diameter of 20 (R)-ginsenoside Rg3 liposomees, enhances the stability of liposome medicament simultaneously；Again after folic acid is to the targeting modification of encapsulating 20 (R)-ginsenoside Rg3 medicinal liposomes, it is achieved the targeted delivery of drugs to cancerous cell.
20 (R) of the present invention-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome has high encapsulation rate to medicine, test result indicate that, the present invention 20 (R)-ginsenoside Rg3 liposome encapsulation can reach more than 90%, the preparation method of the present invention 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament is simple, efficiently, adjunct ingredient safety non-toxic, the tumor cell uptake rate to medicine can be increased, be effectively improved the bioavailability of 20 (R)-ginsenoside Rg3s；The complex lipid Cytotoxicity of preparation is low, have slow-releasing, extend the curative effect of medicine, good evaluation effect has the most been obtained in physics characterizes and extracorporeal biology is studied, gained medicine can enhancing human body immunity power, the research and development strong, for cancer therapy drug of safe and efficient, targeting provide new approach.
Accompanying drawing explanation
Fig. 1 is 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome method specificity test chromatogram；Wherein 1 is 20 (R)-ginsenoside Rg3 liposomees, and 2 is 20 (R)-ginsenoside Rg3 standard substance, and 3 is blank liposome；
Fig. 2 is liposomal particle size scattergram；
Fig. 3 is liposome charge pattern；
Fig. 4 is transmission electron microscope (TEM) testing result figure；Wherein A is that blank liposome TEM detects analysis chart；B is that 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/liposome TEM detects analysis chart；C is that FA10-20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/liposome TEM detects analysis chart；
Fig. 5 is the entrapment efficiency determination result of 203nm wavelength；
Fig. 6 is that 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome of different fat medicine ratio acts on Non-small cell lung carcinoma cell line (H460) the Cytotoxic measurement result that folacin receptor (FR) positive expression rate is higher；Wherein, 1 is blank liposome；2 is the fat medicine 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome than 5:1；3 is the fat medicine 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome than 10:1；4 is the fat medicine 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome than 15:1.
Detailed description of the invention
Being described in detail the present invention below by embodiment, but be not used in and limit the scope of the invention, if no special instructions, the most commercially, if no special instructions, involved method is conventional method for chemical reagent involved in the present invention and medicine.
Embodiment 1
Weighing soybean lecithin to be dissolved in chloroform (1mg/1mL), add cholesterol (soybean lecithin and cholesterol mol ratio are 1:1), concussion makes it be sufficiently mixed uniformly.Dry up the uniform thin film of formation with nitrogen stream, prepare liposome in placement vacuum drying oven overnight.
20 (R)-ginsenoside Rg3 medicines are first dissolved in dehydrated alcohol in advance, are configured to the solution of 2mg/mL, add corresponding volume amount according still further to ratio.It is separately added into ginsenoside Rg3's dehydrated alcohol in the fat medicine ratio than 5:1 and distilled water (ratio is 2:8) soaks about 2h, at 55 DEG C, sonic oscillation makes film be dissolved to clarification repeatedly, prepares medicinal liposome 20 (R)-ginsenoside Rg3 liposome.
The addition final concentration of 10 μ g/mL of folic acid solution, 20 μ g/mL, 30 μ g/mL, 40 μ g/mL are combined 20 (R)-ginsenoside Rg3 liposome medicaments respectively, and sonic oscillation is to clarification at normal temperatures, prepares the medicinal liposome of folate-targeted sex modification.
Embodiment 2
Weighing soybean lecithin to be dissolved in chloroform (1mg/1mL), add cholesterol (soybean lecithin and cholesterol mol ratio are 3:1), concussion makes it be sufficiently mixed uniformly.Dry up the uniform thin film of formation with nitrogen stream, prepare liposome in placement vacuum drying oven overnight.
20 (R)-ginsenoside Rg3 medicines are first dissolved in dehydrated alcohol in advance, are configured to the solution of 2mg/mL, add corresponding volume amount according still further to ratio.Being separately added into 20 (R)-ginsenoside Rg3 dehydrated alcohol in the fat medicine ratio than 10:1 and distilled water (ratio is 2:8) soaks about 2h, at 55 DEG C, sonic oscillation makes film be dissolved to clarification repeatedly, prepares medicinal liposome.
The addition final concentration of 10 μ g/mL of folic acid solution, 20 μ g/mL, 30 μ g/mL, 40 μ g/mL are combined 20 (R)-ginsenoside Rg3 liposome medicaments respectively, sonic oscillation is to clarification at normal temperatures, prepares medicinal liposome FA10-PC-Chol-Rg3, FA20-PC-Chol-Rg3, FA30-PC-Chol-Rg3, FA40-PC-Chol-Rg3 of folate-targeted sex modification.
Embodiment 3
Weighing soybean lecithin to be dissolved in chloroform (1mg/1mL), add cholesterol (soybean lecithin and cholesterol mol ratio are 6:1), concussion makes it be sufficiently mixed uniformly.Dry up the uniform thin film of formation with nitrogen stream, prepare liposome in placement vacuum drying oven overnight.
20 (R)-ginsenoside Rg3 medicines are first dissolved in dehydrated alcohol in advance, are configured to the solution of 2mg/mL, add corresponding volume amount according still further to ratio.Being separately added into 20 (R)-ginsenoside Rg3 dehydrated alcohol in the fat medicine ratio than 15:1 and distilled water (ratio is 2:8) soaks about 2h, at 55 DEG C, sonic oscillation makes film be dissolved to clarification repeatedly, prepares medicinal liposome.
The addition final concentration of 10 μ g/mL of folic acid solution, 20 μ g/mL, 30 μ g/mL, 40 μ g/mL are combined 20 (R)-ginsenoside Rg3 liposome medicaments respectively, and sonic oscillation is to clarification at normal temperatures, prepares the medicinal liposome of folate-targeted sex modification.
Embodiment 4 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol liposomes entrapment efficiency determination
(1) determine detection wavelength: use high performance liquid chromatography
Precision weighs 20 (R)-ginsenoside Rg3 standard substance 20 μ L sample introductions and analyzes, and records peak area.
(2) chromatographic condition
Chromatographic column: AgilentTMODS C18Post (4.6 × 250mm, 5 μm)；Flowing phase: acetonitrile: water (V:V=45:55)；Detection wavelength: 203nm；Flow velocity: 0.7mL/min；Sample size: 20 μ L；Column temperature: room temperature.
(3) method specificity test
Precision pipettes 20 (R)-ginsenoside Rg3 standard substance, soybean lecithin/cholesterol blank liposome, the appropriate 20 μ L sample detection of 20 (R)-ginsenoside Rg3 liposomees respectively, records peak area.As it is shown in figure 1,20 (R)-ginsenoside Rg3 standard substance have the absworption peak of feature at 203nm, retention is 24min.
(4) entrapment efficiency determination method
Ultrafiltration centrifuging separation free drug is used to measure the envelop rate of 20 (R)-ginsenoside Rg3 liposomees.
1. take 20 (the R)-ginsenoside Rg3 liposome solutions 0.3mL prepared, be placed in ultra-filtration centrifuge tube (molecular cut off is 10,000) top sleeve pipe.20000rpm is centrifuged 10min.Take off ultra-filtration centrifuge tube outer sleeve, draw liquid in pipe, measure and separate free drug content after eluting.
2. precision measures 20 (R)-ginsenoside Rg3 liposome 0.5mL, with 0.2 μM of membrane filtration, measures total medicament contg in liposome.The envelop rate of 20 (R)-ginsenoside Rg3 liposomees is calculated by formula.Envelop rate computing formula is as follows:
Wherein EE% represents entrapment efficiency, W0For medicament contg total in liposome, W1For free drug content not encapsulated in liposome.
Embodiment 5 liposomal particle size detects
Made blank liposome, 20 (R)-ginsenoside Rg3 liposomees and the particle diameter of 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome is measured with HORIBA laser nano particle size analyzer (SZ-100).Step is as follows:
Taking 60 μ L blank liposomes to be diluted in 3mL ultra-pure water, ultrasonic 5min makes mix homogeneously, adds in cuvette, it is ensured that do not have aeration testing result, then cuvette is inserted sample cell, close the lid.Selecting detection type Size, arrange test condition, result is shown in accompanying drawing 2.
Embodiment 6 liposome Zeta potential detects
Made blank liposome, 20 (R)-ginsenoside Rg3 liposomees and 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome Zeta potential is measured with HORIBA nano particle size instrument SZ-100.Step is as follows:
Taking 20 μ L liposomal samples to be diluted in 1mL ultra-pure water, ultrasonic 5min makes mix homogeneously, liposomal samples is loaded in electrode, it is ensured that do not have aeration testing result, beyond the Great Wall plug, inserts electrodes in sample cell, closes the lid.Selecting detection type Zeta, result is shown in accompanying drawing 3.
Embodiment 7 liposome complex Morphology observation
1. dripping sample: grip copper mesh with tweezers, take each 8 μ L of the sample prepared with liquid-transfering gun, a droplet sample of dropping is on copper mesh respectively, stands 25-30min.
2. dyeing: suck unnecessary liquid with absorbent paper or filter paper along copper mesh edge, drip the phosphotungstic acid negative staining liquid of 8 μ L 2%, dyeing time 30s with liquid-transfering gun, then suck dyeing liquor with absorbent paper.
3. detection: with transmission electron microscope (TEM) detection sample morphology, result is shown in accompanying drawing 4.
Human tumor cells Proliferation Ability related experiment (mtt assay) of embodiment 8 In vitro culture
By Non-small cell lung carcinoma cell line (H460) cell seeding higher for folacin receptor (FR) positive expression rate in 96 porocyte culture plates, every hole plantation about 1.5 × 105Individual cell, uses RPMI-1640 culture fluid (increase serum and dual anti-) cumulative volume 100 μ L, cell is placed on 37 DEG C, 5%CO2Cellar culture 16～24h in incubator, growth medium is removed during cell density about 80～90%, clean once by equivalent (100 μ L) RPMI-1640 (serum-free) culture medium, then replace with 50 μ LRPMI-1640 (serum-free) culture fluid.
20 (R) embodiment 2 prepared-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicine series etc. is diluted in 50 μ L serum-free RPMI-1640 culture fluid, it is separately added into 96 porocytes and cultivates in plate hole, mix gently, and it is provided with blanc cell comparison, and blank liposome and Rg3 solution are as a control group, it is placed in 37 DEG C, 5%CO2Hatch 24h, every porocyte adds 20 μ L MTT (Sigma, 5mg/mL), 37 DEG C, 5%CO2Hatch cultivation 4h.Carefully discard all culture fluid, dry, add 150 μ L dimethyl sulfoxide (DMSO), 96 porocyte culture plates are put into SUNRISE microplate reader arranges concussion 10min, crystal is made to dissolve, then proceed in SUNRISE microplate reader, measure each hole light absorption value at 570nm, read initial data.
Cleaning Principle based on MTT colorimetry is: the succinate dehydrogenase in living cells mitochondrion can make exogenous MTT be reduced to water-insoluble bluish violet crystallization first collect together (Formazan) and be deposited in cell, and dead cell is without this function, the first that dimethyl sulfoxide (DMSO) can dissolve in cell is collected together, at 570nm wavelength, measure its light absorption value by microplate reader, can indirectly reflect living cells quantity.So, with the light absorption value of blank (non-transfected cells) for 100%, calculate the percentage rate (%) of Transfected cells survival.Computing formula is:
Cell survival rate (%)=[A]Sample/ [A] comparison × 100%
[A]SampleFor the light absorption value of instrument connection, [A]ComparisonLight absorption value for negative blank control wells.
As shown in Figure 6, result shows experimental result, and blank liposome is less, between 80%-95% on cell survival rate impact, it was demonstrated that liposome is a kind of safe and reliable carrier.When 20 (R)-ginsenoside Rg3 liposomees act on H460 cell, decline with the increase cell survival rate of concentration, under same concentrations, cell survival rate under 20 (R)-ginsenoside Rg3 liposome effects is higher than the cell survival rate under 20 (R)-ginsenoside Rg3 independent roles, after illustrating 20 (R)-ginsenoside Rg3s are prepared as liposome medicament, can effectively reduce its toxicity that cell is produced.After 20 (R)-ginsenoside Rg3 liposomees are combined folic acid, cancer cell survival rate reduces, and illustrates that compound folic acid can be effectively improved 20 (the R)-ginsenoside Rg3 liposomees targeting to cancerous cell, medicament curative effect enhancement, has practical significance.
Leading reference
1. leaf is luxuriant and bdautiful, generation, low etc. the preparation of ginsenoside Rg3's liposome, sign and the growth inhibited effect [J] to melanoma cell. and Chinese Journal of New Drugs, 2014,23 (21): 2542-2546.
2. Liu Ji is towering, Zhao Yi, Fu Li etc. the effect [J] of ginsenoside Rg3's inducing cell apoptosis in rat liver cancer lymphatic metastasis model. and China's clinical tumor, 2004,31 (19): 1120-1122.
The highest ship boat .20 (the R)-ginsenoside Rg3s such as Qu Shuxian, the Lv Guangyan research [J] to K562/ADM apoptosis-inducing. Dalian Medical Univ's journal, 2001,23 (3): 172-173.
4.Dongmei Ren,Felix Kratz,Szu-Wen Wang.Engineered drug-protein nanoparticle complexes for folate receptortargeting.Biochem Eng J.2014 August 15；89:33–41.
5.Bhushan S.Pattni,Vladimir V.Chupin,and Vladimir P.Torchilin.New Developments in Liposomal Drug Delivery.Chem.Rev.,2015,115(19),10938–10966.
6.Rongbao Zhao,Ndeye Diop-Bove,and I.David Goldman.Enhanced Receptor Mediated Endocytosis and Cytotoxicity of a Folic Acid-Desacetylvinblastine Monohydrazide Conjugate in a Pemetrexed-Resistant Cell Line Lacking Folate-Specific Facilitative Carriers but with Increased Folate Receptor Expression.Mol Pharmacol.2014,85(2):310–321.
7. yellow English man, Wu Hao, Shen Xizhong. folacin receptor application in cancer target diagnosis and treatment. Fudan Journal [J] (medicine), 2012,39 (1): 74-79.
8. Li Xiang, Zhang Jing, Wang Dongkai, Pan Weisan. the anti-tumor activity [J] of folacin receptor targeting Docetaxel surface-modified liposome. Acta Pharmaceutica Sinica, 2013,48 (7): 1142-1147.
Claims (9)
1. the preparation side of one kind 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament
Method, it is characterised in that comprise the following steps:
(1) being dissolved in chloroform by soybean lecithin, add cholesterol, concussion makes it be sufficiently mixed uniformly, uses nitrogen
Stream dries up the uniform thin film of formation, prepares liposome in placement vacuum drying oven overnight；
(2) it is first dissolved in advance in dehydrated alcohol being configured to 20 (R)-ginsenoside Rg3s by 20 (R)-ginsenoside Rg3s
Solution, adds 20 (R)-ginsenoside Rg3 solution in liposome and distilled water soaks, and sonic oscillation makes repeatedly
Film Fractionation, to clarification, prepares encapsulating 20 (R)-ginsenoside Rg3 liposome；
(3) adding folic acid solution and be combined 20 (R)-ginsenoside Rg3 liposomees, sonic oscillation is to clarification at normal temperatures,
Prepare 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposomal body of folate-targeted sex modification
Thing.
A kind of 20 (R) the most according to claim 1-ginsenoside Rg3/soybean lecithin/cholesterol/leaf
The preparation method of acid liposome medicament, it is characterised in that the soybean lecithin described in step (1) and cholesterol
Mol ratio is 1:1～6:1.
A kind of 20 (R) the most according to claim 1-ginsenoside Rg3/soybean lecithin/cholesterol/leaf
The preparation method of acid liposome medicament, it is characterised in that liposome and 20 (R)-ginsenosides in step (2)
The mass ratio of Rg3 is 5:1～15:1.
A kind of 20 (R) the most according to claim 1-ginsenoside Rg3/soybean lecithin/cholesterol/leaf
The preparation method of acid liposome medicament, it is characterised in that 20 (R)-ginsenoside Rg3 solution in step (2)
Concentration is 2mg/mL.
A kind of 20 (R) the most according to claim 1-ginsenoside Rg3/soybean lecithin/cholesterol/leaf
The preparation method of acid liposome medicament, it is characterised in that 20 (R)-ginsenoside Rg3 solution in step (2)
It is 2:8 with distilled water volume ratio.
A kind of 20 (R) the most according to claim 1-ginsenoside Rg3/soybean lecithin/cholesterol/leaf
The preparation method of acid liposome medicament, it is characterised in that described step (3) folic acid final concentration of
10～40 μ g/mL.
A kind of 20 (R) the most according to claim 1-ginsenoside Rg3/soybean lecithin/cholesterol/leaf
The preparation method of acid liposome medicament, it is characterised in that in step (2) at 45～55 DEG C Under Ultrasonic Vibration repeatedly
Swing and make Film Fractionation to clarification.
8. one kind 20 (R)-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid liposome medicament is by right
1～7 any one method of requirement prepare.
9. 20 (R) as claimed in claim 1-ginsenoside Rg3/soybean lecithin/cholesterol/folic acid
Liposome medicament application in anticancer, antitumor drug.
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| CN112641642A (en) * | 2020-12-31 | 2021-04-13 | 茵素科技(广州)有限公司 | Liposome based on ginsenoside secondary glycoside and application thereof |
| CN112754994A (en) * | 2019-11-05 | 2021-05-07 | 泰州医药城国科化物生物医药科技有限公司 | Ginsenoside liposome and preparation method thereof |
| CN113262310A (en) * | 2021-03-02 | 2021-08-17 | 宿迁市第一人民医院 | Pullulan-modified ginsenoside Rg3Nanostructured lipid carriers and methods of making the same |
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| CN112754994A (en) * | 2019-11-05 | 2021-05-07 | 泰州医药城国科化物生物医药科技有限公司 | Ginsenoside liposome and preparation method thereof |
| CN112641642A (en) * | 2020-12-31 | 2021-04-13 | 茵素科技(广州)有限公司 | Liposome based on ginsenoside secondary glycoside and application thereof |
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| CN115581630A (en) * | 2022-11-02 | 2023-01-10 | 澳门大学 | Ethosome solution, preparation method and application thereof, ethosome cosmeceutical and application thereof |
| CN117017921A (en) * | 2023-10-08 | 2023-11-10 | 吉林农业大学 | Ginsenoside liposome and preparation method thereof |
| CN117017921B (en) * | 2023-10-08 | 2024-03-15 | 吉林农业大学 | Ginsenoside liposome and preparation method thereof |
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