CN102512369A - Glycyrrhetinic acid solid lipid nanoparticles and preparation method for same - Google Patents
Glycyrrhetinic acid solid lipid nanoparticles and preparation method for same Download PDFInfo
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- CN102512369A CN102512369A CN2011104255970A CN201110425597A CN102512369A CN 102512369 A CN102512369 A CN 102512369A CN 2011104255970 A CN2011104255970 A CN 2011104255970A CN 201110425597 A CN201110425597 A CN 201110425597A CN 102512369 A CN102512369 A CN 102512369A
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Abstract
The invention relates to glycyrrhetinic acid solid lipid nanoparticles and a preparation method for the same, belonging to the field of medicinal preparation. The main ingredients of the glycyrrhetinic acid solid lipid nanoparticles disclosed by the invention comprise active raw material glycyrrhetinic acid, medicinal phospholipid, a lipid material and a surfactant. The glycyrrhetinic acid solid lipid nanoparticle solution and the freeze-dried powder injection thereof prepared by the preparation method disclosed by the invention are small in particle diameter, high in entrapment efficiency, good in stability and capable of being used for a plurality of administration routes such as oral administration and injection administration. The glycyrrhetinic acid solid lipid nanoparticles disclosed by the invention can reduce dosage, enhance curative effect and reduce the toxic and side effects of medicine, as well as are suitable for treating a plurality of diseases such as hepatitis, liver cancer, lung cancer, ovarian cancer, gastritis, gastric cancer, leukaemia and aids.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to enoxolone solid lipid nanoparticle and preparation method thereof.
Background technology
(glycyrrhetinic acid is that the main component glycyrrhizic acid of Radix Glycyrrhizae adds water decomposition GA) to enoxolone, also is glycyrrhizic acid active metabolite in vivo, is a kind of pentacyclic triterpenoid.GA claims glycyrrhetinic acid again, and molecular formula is C
30H
46O
4, white needle-like crystals, 289 ~ 291 ℃ of fusing points.Structure is shown below:
Modern study shows enoxolone except that having antiinflammatory, antiulcer, antiallergic, antiviral, blood fat reducing, cough-relieving, relieving asthma, also having the outgrowth effect of antitumor [Liu Bin, Qi Yun the effect such as pain relieving.The pharmaceutical research progress of glycyrrhizic acid and enoxolone.External medical plant amedica fascicle, 2006,21 (3): 100-104.].Discover that enoxolone all has significant inhibitory effect to Hepar Mus cell carcinoma, human liver cancer cell, ehrlich carcinoma, skin carcinoma, malignant melanoma, human breast cancer cell, human leukemia cell, AIDS etc.[1 .18 β-enoxolone such as Huang Wei and glycyrrhizic acid are to human liver cancer cell inhibition of proliferation and induction of differentiation. Chinese Chinese medicine science and technology. and 2009,9 (2): 92-95; 2; Ren é Csuk, Stefan Schwarz, Ralph Kluge; Dieter Str hl. Synthesis and biological activity of some antitumor active derivatives from glycyrrhetinic acid; European Journal of Medicinal Chemistry, 2010,45:5718-5723.].
Enoxolone has caused domestic and international medicine and pharmacology worker's extensive interest.Japan is studying with enoxolone and is treating cancer, existing clinically anti-hepatocarcinoma preparation.The effect and the prevention decayed tooth of " triterpenoid compound " anticancer growth in the Radix Glycyrrhizae also studied by American National DKFZ.The a large amount of import Radix Glycyrrhizaes of western countries are therefrom extracted enoxolone treatment AIDS.In recent years, China also begins to pay attention to and strengthen the research and development of enoxolone.Because enoxolone is a water-insoluble compound, absorption difference in the body of oral back, bioavailability is low, and individual difference is big.As a kind of anticancer preparation, the interior holdup time of prolong drug body also can concentrate in therapentic part it, and for medicament curative effect enhancement, it is significant to improve drug bioavailability.
(solid lipid nanoparticles SLN) is the one type of novel drug-supplying system that grows up early 1990s to solid lipid nanoparticle, and it is the colloidal drug delivery system of particle diameter between 50-1000nm that drug encapsulation is formed in lipoid nuclear.SLN has good stability, the medicine drug loading is high; Advantage [Muller R H, et al.Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art. such as the toxicity that has liposome simultaneously again is low, ability large-scale production, targeting, slow release
Eur J Pharm Biopharm,2000,50 (1): 161-177].
Common solid lipid nanoparticle gets into the body circulation and is prone to engulfed by macrophage identification, in the macrophage body, discharges medicine through the lysosome effect, makes it have passive targeting, gathers easily in liver, spleen, the lymph node.In order to prolong nanoparticle action time in vivo; Usually can carry out PEG to nanoparticle modifies; Increase its surface hydrophilicity; Form sterically hindered; Make nanoparticle escape the identification of mononuclear phagocyte system (MPS), prolong the holdup time of nanoparticle in blood circulation, make it arrive targeting moiety with the more competent time; Thereby reach initiatively the purpose of targeting [Gref R, et al. " Stealth " corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocyt ic uptake and plasma protein adsorption [J].
Colloid Surf B,2000,18 (3-4): 301-313].
Summary of the invention
Technical problem to be solved by this invention provides a kind of stable in properties and is fit to enoxolone solid lipid nanoparticle of suitability for industrialized production and preparation method thereof.Enoxolone solid lipid nanoparticle of the present invention is that enoxolone is wrapped in the lipoid nuclear, has good stability, envelop rate height, can reach effects such as targeting, slow release.Enoxolone solid lipid nanoparticle of the present invention can be through the several different methods preparation; Comprise that emulsifying evaporation-high pressure breast is even or ultrasonic, thin film dispersions-high pressure breast is even or ultrasonic and fusion-even legal system of high pressure breast is equipped with the solid lipid nanoparticle solution of enoxolone, further the caffolding agent lyophilization obtains conveniently storage and the lyophilized powder of the enoxolone solid lipid nanoparticle that transports through adding.
Enoxolone solid lipid nanoparticle of the present invention is wrapped in the lipoid nuclear by the active component of treating effective dose and constitutes.Particularly, wherein each composition quality percentage ratio is following:
Enoxolone 1-10%
Phosphatidase 11 0-80%
Lipoid 5-50%
Surfactant 10-50%
When used surfactant is Polyethylene Glycol (PEG) decorative material in the prescription, be enoxolone long-circulating solid lipid nanoparticle.Polyethyleneglycol modified material commonly used is a kind of in quasi-grease derivative such as Polyethylene Glycol-PHOSPHATIDYL ETHANOLAMINE (mPEG-PE), the hard ester acyl PHOSPHATIDYL ETHANOLAMINE (mPEG-DSPE) of methoxy poly (ethylene glycol)-two, the poly glycol monomethyl ether cholesterol succinate (PEGCHS) of PEG etc.
Said phospholipid can be Ovum Gallus domesticus Flavus lecithin, soybean phospholipid, hydrogenated soya phosphatide, hydrogenated yolk lecithin, phosphatidylinositols, Phosphatidylserine, two PHOSPHATIDYL ETHANOLAMINEs, dipalmitoyl phosphatidyl choline, two palmityl PHOSPHATIDYL ETHANOLAMINEs, DSPC, DSPE etc.
Described lipoid comprises glycerolipid, comprising glyceryl monostearate, glycerol distearate, glyceryl tristearate, myristin, monopalmitin, two tripalmitin, tripalmitin, LAURIN DYNASAN 112, glycerol trioleate, Compritol 888 ATO and composition thereof; Fatty acid is comprising stearic acid, Palmic acid, oleic acid, mountain Yu acid, capric acid and composition thereof; Steroid comprises cholesterol etc.; The waxiness class comprises spermol cetylate, cetyl palmitate and microcrystalline wax.
Said surfactant can be the polyethyleneglycol derivative class, comprises Polyethylene Glycol-PHOSPHATIDYL ETHANOLAMINE (mPEG-PE), the hard ester acyl PHOSPHATIDYL ETHANOLAMINE (mPEG-DSPE) of methoxy poly (ethylene glycol)-two, poly glycol monomethyl ether cholesterol succinate (PEGCHS) etc.; The cholic acid salt comprises sodium cholate, glycosides sodium cholate, sodium taurocholate; The deoxycholic acid salt comprises NaTDC, Taurodeoxycholate sodium; The poloxamer class comprises poloxamer 108,188,407,908; The polysorbate class comprises Tween 80,85,65,60,40.
Controlled with the prepared solid lipid nanoparticle particle diameter of the inventive method, can prepare from 50nm to 800nm according to demand between the nanoparticle of different-grain diameter size and uniform particle diameter.
Above-mentioned enoxolone solid lipid nanoparticle can adopt following method preparation:
Method one: take by weighing enoxolone and phospholipid, lipoid and surfactant in proportion, be dissolved in organic solvent; Reduction vaporization is removed organic solvent, on chamber wall, forms thin film, injects the aqueous solution of pH6-8, makes the film material dissolve aquation 1-2h; Formed Emulsion is the even or ultrasonic nanometer particle size that reduces through the high pressure breast further, after microfilter, promptly gets the solid lipid nanoparticle solution of uniform particle diameter, controlled amount.
Method two: take by weighing enoxolone and phospholipid, lipoid and surfactant in proportion, be dissolved in organic solvent; Under agitation organic solution is directly injected the aqueous solution of pH6-8, made it form emulsion, reduction vaporization is removed organic solvent again; Formed Emulsion is the even or ultrasonic nanometer particle size that reduces through the high pressure breast further, after microfilter, promptly gets the solid lipid nanoparticle solution of uniform particle diameter, controlled amount.
Method three: take by weighing enoxolone and phospholipid, lipoid and surfactant in proportion, the direct heating fusion;
Aqueous solution with pH6-8 under stirring injects fused mixture; Formed Emulsion is the even or ultrasonic nanometer particle size that reduces through the high pressure breast further, after microfilter, promptly gets the solid lipid nanoparticle solution of uniform particle diameter, controlled amount.
For ease of storing and transportation, can enoxolone solid lipid nanoparticle solution be become pressed powder through spray drying or lyophilization, wherein need add excipient.Used excipient comprises mannitol, glucose, cyclodextrin, lactose, sucrose, trehalose, dextran, glycine, sodium chloride etc.
The inventive method, used organic solvent can use common organic solvent, like a kind of or its mixture in methanol, ethanol, ether, acetone, chloroform, ethyl acetate, the dichloromethane etc.
Aqueous solution or phosphate buffer that the aqueous solution of used pH6-8 can use distilled water, water for injection, phosphate buffer and contain beta-schardinger dextrin-, hydroxypropyl or methyl beta-schardinger dextrin-.
Enoxolone solid lipid nano-particle preparation of the present invention can be used for treating diseases such as hepatitis, hepatocarcinoma, breast carcinoma, pulmonary carcinoma, gastritis, gastric cancer, ovarian cancer, leukemia and AIDS.
The inventive method is simple, is prone to sterilization, is fit to large-scale production.Prepared enoxolone solid lipid nanoparticle uniform particle diameter; Envelop rate is high, and good stability is fit to multiple route of administration such as oral or injection; Selected carrier material safety, nontoxic, physiological compatibility good; Can targeting in inflammation or canceration position, and can slowly discharge medicine, reach long lasting purpose.
Description of drawings
Enoxolone solid lipid nanoparticle transmission electron microscope photo among Fig. 1 embodiment 1.
Enoxolone solid lipid nanoparticle particle size distribution figure among Fig. 2 embodiment 1.
Fig. 3 embodiment 1 preparation enoxolone solid lipid nanoparticle is crossed CL-4B gel column elution curve.
The external stripping curve of Fig. 4 enoxolone solid lipid nanoparticle.
The specific embodiment
Embodiment 1
Prescription quality percentage ratio (%)
Enoxolone 5
Ovum Gallus domesticus Flavus lecithin 40
mPEG-DSPE 25
Take by weighing enoxolone, Ovum Gallus domesticus Flavus lecithin, stearic acid and mPEG-DSPE, be dissolved in 2ml ethanol, ultrasonic its dissolving formation clear solution that makes; Be injected in the distilled water of 50 ℃ of 50ml, continue to stir after 30 minutes, place reduction vaporization on the Rotary Evaporators; Further volatilization organic solvent, after the even matter of high pressure homogenization machine circulation 3-5 time, room temperature is put cold then; Cross 0.45 μ m filter membrane, promptly get the colloid solution of enoxolone solid lipid nanoparticle, this colloid solution is translucent, blue opalescence.Measure interior medicament contg with the reversed-phase high-performance liquid chromatography post.Chromatographic column is selected ODS C for use
18Post (4.6*250mm, 5 μ m), mobile phase are methanol-water-glacial acetic acid (volume ratio is 89:10:1), and flow velocity 1.0ml/min detects wavelength 250nm, sample size 10 μ L.Set up the standard curve of enoxolone, the result shows that enoxolone is good at 1 μ g/mL-80 μ g/mL scope class linear relationship.The gained liposome solutions is got 0.2ml cross agarose CL-4B gel column; Phosphate buffer with pH7.4 is an eluent; Amount by every test tube 1ml is collected effluent, asks the calculation envelop rate to reach 94.6% according to elution curve, and the enoxolone liposome is crossed CL-4B gel column elution curve and seen shown in Figure 3.Measure its particle diameter 130.1nm with the Zeta potential particle size analyzer, Zeta potential is-36.2mv.
Embodiment 2
Prescription quality percentage ratio (%)
Enoxolone 1
Ovum Gallus domesticus Flavus lecithin 80
Oleic acid 9
PEGCHS 10
Take by weighing enoxolone, Ovum Gallus domesticus Flavus lecithin, oleic acid and mPEG-DSPE and place the 50ml round-bottomed flask; Add the 2ml chloroform and make its dissolving; 40 ℃ of water-baths place reclaim under reduced pressure organic solvent on the Rotary Evaporators, form a skim at the bottle wall, further place vacuum drying apparatus to remove organic solvent fully.Inject the phosphate buffer aquation 1h of pH8; Placed probe ultrasonic disruption appearance ultrasonic 10-30 minute, and crossed 0.45 μ m filter membrane, gained liposome solutions standardize solution; Add the sucrose of 10% (g/ml), get enoxolone solid lipid nanoparticle lyophilized powder through lyophilization.Getting 0.2ml after the redissolution and cross agarose CL-4B gel column, is eluent with the phosphate buffer of pH7.4, collects effluent by the amount of every test tube 1ml, asks according to elution curve and calculates envelop rate and reach 90%.Same like enoxolone content in the instance 1 usefulness high effective liquid chromatography for measuring solid lipid nanoparticle.Record nanoparticle particle diameter 178.2nm, Zeta potential-30.6mv.
Embodiment 3
Prescription quality percentage ratio (%)
Enoxolone 4
Soybean phospholipid 46
Tripalmitin 5
Poloxamer 50
Take by weighing enoxolone, Ovum Gallus domesticus Flavus lecithin, tripalmitin, poloxamer,, stir following water and inject fused solution 60 ℃ in 60 ℃ of fusion mixings; Continue to stir 30 minutes, after the even matter of high pressure homogenization machine circulation 3-5 time, room temperature is put cold; Cross 0.45 μ m filter membrane,, add 5% (g/ml) mannitol ultrasonic gained solid lipid nanoparticle standardize solution; Lyophilization, the lyophilized powder of enoxolone solid lipid nanoparticle.After adding distil water redissolves, getting 0.2ml and cross agarose CL-4B gel column, is eluent with the phosphate buffer of pH7.4, collects effluent by the amount of every test tube 1ml, asks according to elution curve and calculates envelop rate and reach 98%.Measuring the nanoparticle particle diameter is 231.7nm, and Zeta potential is-33.15mv.
Embodiment 4
Prescription quality percentage ratio (%)
Hydrogenated soya phosphatide 40
Mono stearate glyceryl ester 40
Tween 80 10
Take by weighing enoxolone, Ovum Gallus domesticus Flavus lecithin, mono stearate glyceryl ester and add the 5ml ethyl acetate and make its dissolving, slowly inject the aqueous solution of 60 ℃ of tween 80s under the magnetic agitation, continue to stir after 30 minutes with syringe; Be transferred in the Rotary Evaporators, the volatilization organic solvent is until removing fully, after the even matter of high pressure homogenization machine circulation 3-5 time; Room temperature is put cold, crosses 0.8 μ m filter membrane, promptly gets the colloid solution of enoxolone solid lipid nanoparticle; Get 0.2ml and cross agarose CL-4B gel column; Phosphate buffer with pH7.4 is an eluent, collects effluent by the amount of every test tube 1ml, asks the calculation envelop rate to reach 87.3% according to elution curve.Record particle diameter 384.1nm, Zeta potential-25.12mv.The lactose that adds 10% (g/ml), the spray-dried enoxolone solid lipid nanoparticle pressed powder that gets, this pressed powder can further be prepared into capsule or tablet.
Embodiment 5
Prescription quality percentage ratio (%)
Enoxolone 5
NaTDC 35
Take by weighing enoxolone, hydrogenated yolk lecithin, stearic acid and mPEG-DSPE and place the 50ml round-bottomed flask; Add the 2ml dichloroethanes and make its dissolving; 40 ℃ of water-baths place reclaim under reduced pressure organic solvent on the Rotary Evaporators; Form a skim at the bottle wall, further place vacuum drying apparatus to remove organic solvent fully.Injection contains the aqueous solution aquation 1h of NaTDC, and ultrasonic 10-30 minute, cross 0.45 μ m filter membrane, with gained solid lipid nanoparticle solution standardize solution, ask the calculation envelop rate to reach 92.4% according to elution curve.Record particle diameter 155.3nm, Zeta potential-26.57mv.Add the trehalose of 10% (g/ml), get enoxolone solid lipid nanoparticle lyophilized powder through lyophilization.This lyophilized powder can further be prepared into capsule or tablet.
Embodiment 6
Prescription quality percentage ratio (%)
Enoxolone 3
Hydrogenated yolk lecithin 47
Capric acid 15
mPEG-DSPE 35
Take by weighing enoxolone, hydrogenated yolk lecithin, cholesterol and mPEG-DSPE and place the 50ml round-bottomed flask; Add the 2ml chloroform and make its dissolving; 40 ℃ of water-baths place reclaim under reduced pressure organic solvent on the Rotary Evaporators; Form a skim at the bottle wall, further place vacuum drying apparatus to remove organic solvent fully.Injection contains the aqueous solution aquation 1h of the pH8 of 0.1M beta-schardinger dextrin-, and too high extrusion depressor behind the multigelation 3 times with gained solid lipid nanoparticle solution standardize solution, is asked according to elution curve and to be calculated envelop rate and reach 95.7%.Record particle diameter 152.6nm, Zeta potential-23.15mv.
Embodiment 7The mensuration of enoxolone solid lipid nano release in vitro degree.The PBS solution that contains the alcoholic acid pH7.4 of sodium lauryl sulphate and 30% (g/ml) of 0.5% (g/ml) with 200mL is medium, and precision pipettes 2mL enoxolone solid lipid nanoparticle solution, places bag filter (molecular cut off 3000), magnetic agitation.Discharge liquid 0.5mL respectively at getting in 0.5,1,2,3,4,6,8,10,12,24,48 hour, cross the microporous filter membrane of 0.45 μ m, carry out HPLC and analyze, replenish synthermal dissolution medium 1mL simultaneously.Measure GA concentration, calculating cumulative discharges percentage rate.Q (%)=C by formula
t/ C
0* 100% calculates burst size.C wherein
tBe the medication amount that discharges, C
0Be initial drug amount in the liposome.With time is abscissa, and the cumulative release percentage rate is a vertical coordinate, draws external release curve, sees Fig. 4 for details.The gained data are carried out match by one-level, Higuchi and Weibull equation, and dependent equation and degree of fitting are seen table 1.The result shows that its release rule more meets first-order rate process, explains that enoxolone mainly discharges in dissolution medium with the mode of passive diffusion in solid lipid nano.
The external release curve fitting of table 1 enoxolone solid lipid nanoparticle
| Model | Regression equation | Degree of fitting (γ 2 ) |
| The one-level equation | Y=0.0467X+4.4998 | 0.9952 |
| The Higuchi equation | Q=13.556t 1/2+0.5998 | 0.9923 |
| The Weibull equation | Y=0.6824X-2.0195 | 0.9846 |
Embodiment 8The enoxolone liposome is to the cytotoxicity of HCC SK-HEP-1
The SK-Hep-1 HCC of taking the logarithm and increasing is with 0.5 * 10
4Plant in 96 orifice plates; Select the positive contrast of free drug dexamethasone for use, dexamethasone, enoxolone and enoxolone liposome are diluted to a series of concentration by the multiple of 1:4, add 96 orifice plates of having planted HCC; Parallel 3 holes of doing of various conditions are in 37 ℃, 5%CO
2Cultivate 48h in the incubator of saturated humidity, every hole adds 20 μ L 5mg.mL
-1MTT solution, continue to cultivate 4h, inhale and remove culture fluid; Every hole adds dimethyl sulfoxine 200 μ L, and vibration is dissolving fully, places the absorbance of measuring every hole on the ELIASA under the 570nm wavelength; With the mapping of concentration logarithm value pair cell survival rate, calculate the IC of each sample to HCC SK-HEP-1
50Value is respectively free drug dexamethasone 199 ± 10 μ M, enoxolone 32 ± 7 μ M and enoxolone liposome 141 ± 5 μ M.
Embodiment 9The enoxolone liposome is to the cytotoxicity of leukaemia MV4-11
The acute myelocytic leukemia cell MV4-11 that takes the logarithm and increase is with 1 * 10
5Plant in 96 orifice plates; Select free drug YANSUAN DUOROUBIXING (amycin), the positive contrast of dexamethasone for use; Amycin, dexamethasone, enoxolone and enoxolone liposome are diluted to a series of concentration by the multiple of 1:4; Add 96 orifice plates of having planted the leukaemia, parallel 3 holes of doing of various conditions are in 37 ℃, 5%CO
2Cultivate 48h in the incubator of saturated humidity, every hole adds 20 μ L 5mg.mL
-1MTT solution, continue to cultivate 4h, inhale and remove culture fluid; Every hole adds dimethyl sulfoxine 200 μ L, and vibration is dissolving fully, places the absorbance of measuring every hole on the ELIASA under the 570nm wavelength; With the mapping of concentration logarithm value pair cell survival rate, calculate the IC of each sample dialogue disorders of blood cell MV4-11
50Value is respectively free drug amycin 0.16 ± 0.1 μ M, dexamethasone 25 ± 3 μ M, enoxolone 20 ± 5 μ M and enoxolone liposome 63 ± 4 μ M.
Claims (8)
1. enoxolone solid lipid nanoparticle is wrapped in the lipoid nuclear by the active component of treatment effective dose and constitutes, and it is characterized in that wherein each composition quality percentage ratio is following:
Enoxolone 1-10%
Phosphatidase 11 0-80%
Lipoid 5-80%
Surfactant 10-50%.
2. enoxolone solid lipid nanoparticle according to claim 1 is characterized in that, said phospholipid is natural phospholipid or synthetic phospholipid.
3. enoxolone solid lipid nanoparticle according to claim 1 is characterized in that described lipoid comprises glycerolipid, fatty acid, steroid or waxiness class.
4. enoxolone solid lipid nanoparticle according to claim 1 is characterized in that, said surfactant is the polyethyleneglycol derivative class, cholic acid salt, deoxycholic acid salt, poloxamer class or polysorbate class.
5. enoxolone solid lipid nanoparticle according to claim 1 is characterized in that its particle diameter is between 50-1000nm.
6. the method for preparing of the said enoxolone solid lipid nanoparticle of claim 1 is characterized in that, takes by weighing enoxolone and phospholipid, lipoid and surfactant in proportion, is dissolved in organic solvent; Reduction vaporization is removed organic solvent, on chamber wall, forms thin film, injects the aqueous solution of pH6-8, makes the film material dissolve aquation 1-2h; Formed Emulsion is the even or ultrasonic nanometer particle size that reduces through the high pressure breast further, after microfilter, promptly gets the solid lipid nanoparticle solution of uniform particle diameter, controlled amount.
7. the method for preparing of the said enoxolone solid lipid nanoparticle of claim 1 is characterized in that, takes by weighing enoxolone and phospholipid, lipoid and surfactant in proportion, is dissolved in organic solvent; Under agitation organic solution is directly injected the aqueous solution of pH6-8, made it form emulsion, reduction vaporization is removed organic solvent again; Formed Emulsion is the even or ultrasonic nanometer particle size that reduces through the high pressure breast further, after microfilter, promptly gets the solid lipid nanoparticle solution of uniform particle diameter, controlled amount.
8. the method for preparing of the said enoxolone solid lipid nanoparticle of claim 1 is characterized in that, takes by weighing enoxolone and phospholipid, lipoid and surfactant in proportion, the direct heating fusion; Aqueous solution with pH6-8 under stirring injects fused mixture; Formed Emulsion is the even or ultrasonic nanometer particle size that reduces through the high pressure breast further, after microfilter, promptly gets the solid lipid nanoparticle solution of uniform particle diameter, controlled amount.
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| CN104045823A (en) * | 2014-06-26 | 2014-09-17 | 武汉大学 | Glycyrrhetinic acid derivative, and preparation method and application thereof |
| WO2018210224A1 (en) * | 2017-05-15 | 2018-11-22 | 王晓辉 | Applications of triptolide and derivative thereof in preparing medicament for treating and/or preventing lung-damaging diseases |
| CN113387996A (en) * | 2021-07-15 | 2021-09-14 | 郑州大学 | Pentacyclic triterpene biguanide conjugate and preparation method and application thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102727793A (en) * | 2012-06-29 | 2012-10-17 | 海南美兰史克制药有限公司 | Yikunning pharmaceutical composition solid lipid nanosphere preparation |
| CN104045823A (en) * | 2014-06-26 | 2014-09-17 | 武汉大学 | Glycyrrhetinic acid derivative, and preparation method and application thereof |
| WO2018210224A1 (en) * | 2017-05-15 | 2018-11-22 | 王晓辉 | Applications of triptolide and derivative thereof in preparing medicament for treating and/or preventing lung-damaging diseases |
| CN113387996A (en) * | 2021-07-15 | 2021-09-14 | 郑州大学 | Pentacyclic triterpene biguanide conjugate and preparation method and application thereof |
| CN113387996B (en) * | 2021-07-15 | 2022-06-07 | 郑州大学 | Pentacyclic triterpene biguanide conjugate and preparation method and application thereof |
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Application publication date: 20120627 |