CN106511422A - Liver targeting Cichorium glandulosum total sesquiterpene magnetic liposome nanoparticle and preparation method thereof - Google Patents
Liver targeting Cichorium glandulosum total sesquiterpene magnetic liposome nanoparticle and preparation method thereof Download PDFInfo
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Abstract
The present invention provides a liver targeting Cichorium glandulosum total sesquiterpene magnetic liposome nanoparticle and a preparation method thereof, the liver targeting Cichorium glandulosum total sesquiterpene magnetic liposome nanoparticle is prepared from Cichorium glandulosum total sesquiterpene extract, lecithin, cholesterol, absolute ethanol, a phosphate buffer with pH of 6.8-7.4 and a magnetic nanosuspension solution, the Cichorium glandulosum total sesquiterpene extract as a model drug is packed in liposomes by a nano liposome technology, and the magnetic nanosuspension solution is additionally added for preparation of the liver targeting new drug carrier magnetic liposome nanoparticle. The drug is combined with nano magnetic particles, and is controlled by a magnetic guidance system for targeted drug delivery to a diseased region, and effective blood-drug concentration of target sites is improved, so that the therapeutic effect is enhanced, and adverse drug reaction is reduced. The drug carrier also has the nanoparticle function, when the drug carrier enters the body, directional movement and positioning concentration in the body of liposome nanoparticles are guided by in-vitro magnetic effect, drug targeting performance and specificity are enhanced, and a high-efficiency low-toxicity quick-effect therapeutic effect can be achieved.
Description
Technical field
The present invention relates to pharmaceutical carrier technical field, and in particular to a kind of saussurea intybus total sesquiterpene magnetic lipid of Liver targeting
Body nanoparticle and preparation method.
Background technology
Liver is the most important removing toxic substances internal organs of human body, easily occur various metabolics, infectious disease and constitutional and after
The property sent out tumor.The hepatic disease that hepatic injury causes has become commonly encountered diseases, frequently-occurring disease, and more seriously the liver function of its induction declines
Exhaust with hepatic encephalopathy etc., M ＆ M is high.
Nano-medicament carrier of the liposome (liposomes) as common targeting preparation, according to the carrier that medicine is combined
Medicine is transported to specific therapentic part, but the pharmaceutical carrier being prepared is past by the difference to body disease position affinity
It is poor toward excessive or specificity, which is limited as the application of effective ingredient in Chinese carrier.
Saussurea intybus total sesquiterpene extract in the present invention is obtained from extraction purification in Xinjiang characteristic resource saussurea intybus
One class natural sesquiterpene active component, reduction chemical liver injury that can be different degrees of and Immune liver injury mice blood
AST, ALT and TBIL level and liver coefficient in clear.At present, saussurea intybus total sesquiterpene extract not yet has preferable Targeting Effect
Targeting preparation.
The content of the invention
Present invention aim at, there is provided a kind of saussurea intybus total sesquiterpene magnetic liposome nanoparticle of Liver targeting and preparation side
Method, be by saussurea intybus total sesquiterpene extract, lecithin, cholesterol, dehydrated alcohol, the phosphate buffer of pH6.8-7.4 and
Magnetic Nano suspension is constituted, and is adopted with saussurea intybus total sesquiterpene extract as model drug, by nano-lipid body technique bag
It is encapsulated in liposome, then additional magnetic Nano liquid is prepared into the new drug carrier magnetic liposome nanoparticle with Liver targeting.
Medicine is combined with nano level magnetic particle, is controlled (i.e. by the effect of externally-applied magnetic field) by magnetic guidance system, by medicine
Thing targeted improves the effective blood drug concentration of target site to diseased region, so as to strengthen therapeutic effect, mitigates adverse drug anti-
Should.The drug administration carrier has nanoparticle function simultaneously, after which enters in vivo, guides liposome nanometer using external magnetic field effect
Concentrate in vivo by displacement and positioning for grain, strengthens the targeting and specificity of medicine, so as to reach efficient, quick-acting, low toxicity
Therapeutic effect.Technical problem to be solved is that saussurea intybus total sesquiterpene extract is developed into a kind of new liver targeted drug delivery to carry
Body, to strengthen the selectivity and targeting at liver pathological changes position, improves bioavailability.
The saussurea intybus total sesquiterpene magnetic liposome nanoparticle of Liver targeting of the present invention and preparation method, with 10g be
Radix, by saussurea intybus total sesquiterpene extract 40-160mg, lecithin 800-3500mg, cholesterol 160-640mg, dehydrated alcohol
Phosphate buffer 1-the 10ml and magnetic Nano suspension 1-10ml of 2-20ml, pH6.8-7.4 makes.
The saussurea intybus total sesquiterpene magnetic liposome nanoparticle of described Liver targeting, it is with 10g as radix, total again by saussurea intybus
Half terpenoid extract 60-100mg, lecithin 1400-1800mg, cholesterol 300-340mg, dehydrated alcohol 8-15ml, pH6.8-7.4
Phosphate buffer 2-4ml and magnetic Nano suspension 2-4ml make.
Lecithin is soybean lecithin and hydrogenated soy phosphatidyl choline, Egg Yolk Lecithin (PC-98T) or phosphatidylcholine.
A kind of preparation method of the saussurea intybus total sesquiterpene magnetic liposome nanoparticle of Liver targeting, follow these steps to carry out：
A, lecithin 800-3500mg, cholesterol 160-640mg and saussurea intybus total sesquiterpene extract 40-160mg are added
Enter in dehydrated alcohol 2-20ml, ultrasound makes to be uniformly dissolved, wherein lecithin is soybean lecithin and hydrogenated soy phosphatidyl choline, egg
Yellow lecithin or phosphatidylcholine；
In b, the phosphate buffer 1-10ml of the pH 6.8-7.4 that the solution of step a is added to 60 DEG C of constant temperature, in temperature
Magnetic agitation 1h under 40-60 DEG C of water bath condition of degree, removes ethanol, then ultrasonic 150 times with 400W ultrasonic cell disruptes instrument probe, obtains
To saussurea intybus total sesquiterpene extract conventional liposome；
C, the conventional liposome for obtaining step b are injected into 2% Tween 80 by the syringe needle with fine pore or pipeline
Fe3O4In magnetic nano particle suspension, injection rate is 1-3mL/min, constant temperature oscillation, the water-bath after liposome completion of dropping
30min, is separated after standing adsorption 20-40min, and lyophilization obtains the magnetic liposome nanometer that particle diameter is 30-150nm
Grain.
Described magnetic liposome nanoparticle, diameter of particle is 30-150nm, average envelop rate (n=3) more than 90%.
Saussurea intybus total sesquiterpene magnetic liposome nanoparticle of the present invention, its model drug saussurea intybus total sesquiterpene are carried
The preparation method for taking thing is：
Saussurea intybus medicinal material drying aerial partss are taken, is cleaned, cut into the segment of 2-3cm, plus the 40% of 15 times of medical material weight
Ethanol, 80 DEG C of reflux, extract, are secondary, 3 hours every time, united extraction liquid, and filtration, decompression filtrate recycling ethanol are simultaneously concentrated into every mL
Equivalent to the concentrated solution of crude drug 0.3g, add on processed good HPD100 macroporous adsorptive resins, adsorb 6 hours, first with 4 times
The deionized water rinsing of column volume, then with 60% ethanol elution of 5 times of column volumes, collect containing alcohol eluen, reclaim ethanol, decompression
Dry extract is concentrated and be vacuum dried into, is crushed, crossed 100 mesh sieves, obtain final product.
A kind of preparation method of the saussurea intybus total sesquiterpene magnetic liposome nanoparticle of Liver targeting of the present invention, the party
Fe is prepared using ultrasound precipitation method in method3O4Magnetic Nano suspension, concrete operations follow these steps to carry out：
Under room temperature, weigh 0.5gPEG-6000 and be dissolved in deionized water, be placed in three-necked bottle, take under nitrogen protection, and
In advance evacuation reduces ferrous oxidation, ferrous chloride and ferric chloride solution is pressed Fe reducing the impact of oxygen in air2+/
Fe3+1:2 (mol/mol) add PEG-6000 solution, stirring to make mix homogeneously, and stirring is lower to add 2mol/L sodium hydroxide solutions to adjust
PH is then heated to temperature 60 C to 11, maintains the temperature to stir 30min；
After completion of the reaction three-necked bottle is put and accelerate on Magnet Fe3O4Magnetic nano particle is precipitated, and sucks supernatant liquid, N2Protection
Under, lower floor Fe3O410ml deionized waters are added in magnetic nano particle precipitation suspension, in magnetic force after 100mA ultrasonic disperse 15min
Stirring is lower fully to wash, repeated washing to Fe3O4Magnetic nano particle suspension pH is neutrality；
Fe obtained in laser particle analyzer detection3O4The mean diameter of magnetic nano particle is visible under 20nm or so, transmission electron microscope
Magnetic nano particle is in ball-shaped and shows a monodisperse distribution.
By comparing saussurea intybus total sesquiterpene magnetic lipid prepared by saussurea intybus total sesquiterpene extract solution and the present invention
The release in vitro of body nanoparticle solution is investigated, and is as a result shown：Saussurea intybus total sesquiterpene extract solution cumulative release speed is very fast,
During 4h, drug accumulation release percentage rate reaches 96.4%；And saussurea intybus total sesquiterpene magnetic liposome nanoparticle in same time
Cumulative release amount is far below extract solution, is 93.1% when being only 42.2%, 12h during 4h, and its rate of releasing drug compares
Slowly, illustrate that saussurea intybus total sesquiterpene magnetic liposome nanoparticle has obvious slow release with respect to saussurea intybus total sesquiterpene extract
Effect.
The technical problem to be solved in the present invention is, by saussurea intybus total sesquiterpene extract be developed into a kind of new Liver targeting to
Drug carrier, to strengthen the selectivity and targeting at liver pathological changes position, improves bioavailability.Described magnetic liposome nanoparticle
It is that saussurea intybus total sesquiterpene extract is encapsulated in additional magnetic Nano liquid in liposome to be prepared from.The magnetic liposome of preparation
Nanoparticle significantly improves abundance of the effective ingredient lactucin in mice in-vivo tissue, especially after intravenous injection administration
Which is in liver.Compared with conventional liposome, mean residence time (MRT) of the magnetic liposome nanoparticle in liver is increased
4 times, content improves about 42 times.Show that magnetic liposome nanoparticle changes effective ingredient distribution in animal body and disappears
Except process, extend effective ingredient circulation in vivo and action time, improve effective ingredient bioavailability in vivo, have
There are certain specificity and targeting.
The positive effect of the present invention is：Saussurea intybus total sesquiterpene extract yield low (about 0.8%), common form of administration
Effective blood drug concentration is relatively inaccessible in target site.And after being developed into magnetic liposome nanoparticle, change total times of saussurea intybus
Active component distribution in animal body in half terpenoid extract, extends active component circulation in vivo and action time, improves
Active component bioavailability in vivo, specificity and targeting been significantly enhanced.
The present invention had so both eliminated the conventional toxicity of document larger using dehydrated alcohol as the organic solvent of phospholipid
Organic reagent chloroform or methanol residual, reduce environmental pollution again, reduce production cost, and protect operator's
Safety, more suitable for industrialized production.
Description of the drawings
Fig. 1 is the grain size distribution of saussurea intybus total sesquiterpene magnetic liposome nanoparticle of the present invention, it is seen that mean diameter is
About 65nm, meets normal distribution.
Fig. 2 is the transmission electron microscope picture of saussurea intybus total sesquiterpene magnetic liposome nanoparticle of the present invention, it is seen that substantially wrapped at center
Magnetic nano particle is wrapped with, particle size range is less than 100nm, is evenly distributed.
Fig. 3 be intravenous saussurea intybus total sesquiterpene magnetic liposome nanoparticle of the present invention in mouse tissue organ when it is m-
Concentration change, i.e., internal tissue distribution figure, it is seen that magnetic nano particle has certain hepatic targeting, wherein 1 is 0.083 little
When, 2 be 0.167 hour, 3 be 0.333 hour, 4 be 0.5 hour, 5 be 1 hour, 6 be 2 hours, 7 be 4 hours, 8 be 6 hours, 9
For 12 hours.
Specific embodiment
The present invention is further described by following examples, it should be appreciated that these embodiments are without departing substantially from the present invention
Technology under the premise of, any change or change that those of ordinary skill in the art made for the present invention easily realize falls within
Within the claims of the present invention.
Embodiment 1
Precision weighs soybean lecithin 1200mg, hydrogenated soy phosphatidyl choline 200mg, cholesterol 300mg, the total sesquialter of saussurea intybus
Terpenoid extract 60mg is put in conical flask, adds 8ml dehydrated alcohol, ultrasound to make dissolving；
Resulting solution is added in pH=7.0 phosphate buffered solution 4ml of 60 DEG C of constant temperature, in temperature 60 C water-bath bar
Magnetic agitation 1h under part, removes ethanol, then with ultrasonic cell disrupte instrument probe ultrasound (400W) 150 times, that is, obtains common lipid
Body；
Conventional liposome solution is injected into into 5ml 2% tween by the syringe needle with fine pore with the flow velocity of 2mL/min
80 Fe3O4In magnetic nano particle suspension, constant temperature oscillation, 55 DEG C of water-bath 30min of temperature after liposome solutions completion of dropping,
Separated after standing adsorption 30min, lyophilization, particle diameter is obtained for 30nm, hair of the average envelop rate for 91.2% (n=3)
Herba Cichorii total sesquiterpene magnetic liposome nanoparticle.
Embodiment 2
Precision weighs soybean lecithin 1400mg, hydrogenated soy phosphatidyl choline 400mg, cholesterol 340mg, the total sesquialter of saussurea intybus
Terpenoid extract 100mg is put in conical flask, adds 15ml dehydrated alcohol, ultrasound to make dissolving；
Resulting solution is added in pH=6.8 phosphate buffered solution 4ml of 60 DEG C of constant temperature, in temperature 50 C water-bath bar
Magnetic agitation 1h under part, removes ethanol, then ultrasonic 150 times with 400W ultrasonic cell disruptes instrument probe, that is, obtain conventional liposome；
Conventional liposome solution is injected into into 4ml 2% tween by the pipeline with fine pore with the flow velocity of 1mL/min
80 Fe3O4In magnetic nano particle suspension, constant temperature oscillation, 55 DEG C of water-bath 30min of temperature after liposome solutions completion of dropping,
Separated after standing adsorption 30min, lyophilization, particle diameter is obtained for 50nm, hair chrysanthemum of the average envelop rate for 92% (n=3)
Lettuce total sesquiterpene magnetic liposome nanoparticle.
Embodiment 3
Precision weighs soybean lecithin 1300mg, hydrogenated soy phosphatidyl choline 300mg, cholesterol 320mg, the total sesquialter of saussurea intybus
Terpenoid extract 80mg is put in conical flask, adds 10ml dehydrated alcohol, ultrasound to make dissolving；
Resulting solution is added in pH=7.4 phosphate buffered solution 2ml of 60 DEG C of constant temperature, in temperature 60 C water-bath bar
Magnetic agitation 1h under part, removes ethanol, then ultrasonic 150 times with 400W ultrasonic cell disruptes instrument probe, that is, obtain conventional liposome；
Conventional liposome solution is injected into into 2ml 2% tween by the syringe needle with fine pore with the flow velocity of 1mL/min
80 Fe3O4In magnetic nano particle suspension, constant temperature oscillation, 55 DEG C of water-bath 30min of temperature after liposome solutions completion of dropping,
Separated after standing adsorption 30min, lyophilization, particle diameter is obtained for 80nm, hair of the average envelop rate for 92.4% (n=3)
Herba Cichorii total sesquiterpene magnetic liposome nanoparticle.
Embodiment 4
Precision weighs soybean lecithin 800mg, hydrogenated soy phosphatidyl choline 100mg, cholesterol 160mg, the total sesquialter of saussurea intybus
Terpenoid extract 40mg is put in conical flask, adds 5ml dehydrated alcohol, ultrasound to make dissolving；
Resulting solution is added in pH=7.4 phosphate buffered solution 2ml of 60 DEG C of constant temperature, in temperature 45 C water-bath bar
Magnetic agitation 1h under part, removes ethanol, then ultrasonic 150 times with 400W ultrasonic cell disruptes instrument probe, obtains conventional liposome；
Conventional liposome solution is injected into 4ml 2% by the pipeline with fine pore with the flow velocity of 1.5mL/min to tell
The Fe of temperature 803O4In magnetic nano particle suspension, constant temperature oscillation, 55 DEG C of water-baths of temperature after liposome solutions completion of dropping
30min, is separated after standing adsorption 30min, lyophilization, and it is 120nm to obtain particle diameter, and average envelop rate is 91.7% (n=
3) saussurea intybus total sesquiterpene magnetic liposome nanoparticle.
Embodiment 5
Precision weighs soybean lecithin 3000mg, hydrogenated soy phosphatidyl choline 500mg, cholesterol 640mg, the total sesquialter of saussurea intybus
Terpenoid extract 160mg is put in conical flask, adds 20ml dehydrated alcohol, ultrasound to make dissolving；
Resulting solution is added in pH=7.0 phosphate buffered solution 5ml of 60 DEG C of constant temperature, in temperature 50 C water-bath bar
Magnetic agitation 1h under part, removes ethanol, then ultrasonic 150 times with 400W ultrasonic cell disruptes instrument probe, obtains conventional liposome；
Conventional liposome solution is injected into into 5ml 2% tween by the syringe needle with fine pore with the flow velocity of 3mL/min
80 Fe3O4In magnetic nano particle suspension, constant temperature oscillation, 55 DEG C of water-bath 30min of temperature after liposome solutions completion of dropping,
Separated after standing adsorption 40min, lyophilization, particle diameter is obtained for 150nm, hair of the average envelop rate for 93.1% (n=3)
Herba Cichorii total sesquiterpene magnetic liposome nanoparticle.
Embodiment 6
Precision weighs Egg Yolk Lecithin (PC-98T) 2000mg, cholesterol 200mg, saussurea intybus total sesquiterpene extract 60mg and puts conical flask
In, add 15ml dehydrated alcohol, ultrasound to make dissolving；
Resulting solution is added in pH=6.8 phosphate buffered solution 5ml of 60 DEG C of constant temperature, in temperature 50 C water-bath bar
Magnetic agitation 1h under part, removes ethanol, then ultrasonic 150 times with 400W ultrasonic cell disruptes instrument probe, obtains conventional liposome；
Conventional liposome solution is injected into into 4ml 2% tween by the syringe needle with fine pore with the flow velocity of 2mL/min
80 Fe3O4In magnetic nano particle suspension, constant temperature oscillation, 55 DEG C of water-bath 30min of temperature after liposome solutions completion of dropping,
Separated after standing adsorption 30min, lyophilization, particle diameter is obtained for 100nm, hair of the average envelop rate for 92.2% (n=3)
Herba Cichorii total sesquiterpene magnetic liposome nanoparticle.
Embodiment 7
Precision weighs phosphatidylcholine 1200mg, cholesterol 160mg, saussurea intybus total sesquiterpene extract 50mg and puts conical flask
In, add 10ml dehydrated alcohol, ultrasound to make dissolving；
Resulting solution is added in pH=7.4 phosphate buffered solution 3ml of 60 DEG C of constant temperature, in temperature 60 C water-bath bar
Magnetic agitation 1h under part, removes ethanol, then ultrasonic 150 times with 400W ultrasonic cell disruptes instrument probe, obtains conventional liposome；
Conventional liposome solution is injected into into 3ml 2% tween by the syringe needle with fine pore with the flow velocity of 1mL/min
80 Fe3O4In magnetic nano particle suspension, constant temperature oscillation, 55 DEG C of water-bath 30min of temperature after liposome solutions completion of dropping,
Separated after standing adsorption 30min, lyophilization, particle diameter is obtained for 110nm, hair of the average envelop rate for 91.6% (n=3)
Herba Cichorii total sesquiterpene magnetic liposome nanoparticle.
Embodiment 8
Internal effect experiment
Research protection of the saussurea intybus total sesquiterpene magnetic liposome nanoparticle to acute and immunologic liver injury in Mice Body
Effect.
Experimental agents
By reagent：Saussurea intybus total sesquiterpene extract (SRF, Chinese Academy of Sciences's Xinjiang physiochemical techniques institute self-control), saussurea intybus
Total sesquiterpene magnetic liposome nanoparticle (SRF-MLN, institute of Materia Medica,Chinese Academy of Medical Sciences self-control)；Positive control drug：Connection
Benzene dibasic acid esters drop pill (Beijing XieHe medicine Factory's production).
Laboratory animal
7-9 week Kunming kind female mices, 18～22g of body weight, purchased from Beijing Vital River Experimental Animals Technology Co., Ltd.,
Animal quality certification number：SCXK (capital) 2014-0023.
Mice group and administration
Anti- acute liver damage：Kunming mouse, male and female half and half, be randomly divided into normal group, model group, SRF solution groups, height,
In, the SRF-MLN solution of low dosage and positive drug group (bifendate), 6 per group.From modeling 1d, tail vein injection SRF
(25mg/kg) solution and the basic, normal, high dosage of SRF-MLN (6.25mg/kg, 12.5mg/kg, 25mg/kg), gavage bifendate
Drop pill (150mg/kg), successive administration 10d, blank control group and model group inject isopyknic normal saline respectively.
Anti-immune hepatic injury：In addition to normal group mice, remaining each group 15min mouse tail vein injections before 1d administrations
After BCG normal saline solutions, from modeling 1d, tail vein injection SRF (25mg/kg) solution and basic, normal, high dose of SRF-MLN
Amount (6.25mg/kg, 12.5mg/kg, 25mg/kg), gavage bifendate (150mg/kg), successive administration 10d, blank control group
Isopyknic normal saline is injected respectively with model group, and after last dose 15min, mouse tail vein injection LPS physiology salts are water-soluble
Liquid, fasting 24h post processing samples.
Sample collection and process
The fasting 24h after last dose, takes blood from mice vena ophthalmica clump, collects serum, deposits in 4 DEG C, after eyeball takes blood
Drawing neck puts to death mice, rapid to dissect, clip right lobe of liver same area, adds 4 DEG C of pre- cold salines to grind in homogenizer after cleaning
Mill, prepares 10% and is homogenized in ice bath, 3000r/min centrifugation 15min take supernatant, determine content according to kit specification.Together
When, right lobe of liver same area is taken, -80 DEG C of refrigerator storages of temperature are fixed or be placed in 4% paraformaldehyde.
Biochemical indicator is detected
By in blood collecting and coagulant pipe, 4 DEG C of standing 30min of temperature are centrifuged 20min in 1500rpm, are drawn with liquid-transfering gun
The faint yellow serum in upper strata, subsequently according to each detection kit, MDA and SOD in measure serum alt and AST regulating liver-QI homogenates
Content.
Table 1SRF-MLN is to CCl4Cause the impact (n=6) of acute liver model
Compare with blank group,△△P<0.01, compare with model group,*P<0.05,**P<0.01
Impacts (n=6) of the table 2SRF-MLN to immunological liver injury model
Compare with blank group,△△P<0.01, compare with model group,*P<0.05,**P<0.01
SRF-MLN can substantially above-mentioned 2 kinds of liver damage animal models ALT, AST activity of antagonism, the rising of liver MDA contents and
The reduction of SOD activity, with the effect for suppressing hepatocyte lipid peroxidation, stable liver plasma membrane structure；Hepatic tissue SOD can be improved
Vigor, strengthen hepatocellular oxidation resistance, so as to resist hepatocellular oxidative stress and peroxidating, make hepatocyte from
Damage, so as to reach the purpose for the treatment of hepatic injury.
Claims (4)
1. the saussurea intybus total sesquiterpene magnetic liposome nanoparticle of a kind of Liver targeting, it is characterised in that with 10g as radix, by hair chrysanthemum
Lettuce total sesquiterpene extract 40-160 mg, lecithin 800-3500 mg, cholesterol 160-640 mg, dehydrated alcohol 2-20 ml,
- 10 ml of phosphate buffer 1 and magnetic Nano suspension 1-10 ml of pH 6.8-7.4 makes.
2. the saussurea intybus total sesquiterpene magnetic liposome nanoparticle of Liver targeting as claimed in claim 1, it is characterised in that with 10g
For radix, by saussurea intybus total sesquiterpene extract 60-100 mg, lecithin 1400-1800 mg, cholesterol 300-340 mg, nothing
Water-ethanol 8-15 ml, the phosphate buffer 2-4ml of pH 6.8-7.4 and magnetic Nano suspension 2-4ml make.
3. the saussurea intybus total sesquiterpene magnetic liposome nanoparticle of Liver targeting as claimed in claim 1 or 2, it is characterised in that
Lecithin is soybean lecithin and hydrogenated soy phosphatidyl choline, Egg Yolk Lecithin (PC-98T) or phosphatidylcholine.
4. the preparation method of the saussurea intybus total sesquiterpene magnetic liposome nanoparticle of a kind of Liver targeting, it is characterised in that by following step
Suddenly carry out：
A, lecithin 800-3500 mg, cholesterol 160-640 mg and saussurea intybus total sesquiterpene extract 40-160 mg are added
To in dehydrated alcohol 2-20 ml, ultrasound makes to be uniformly dissolved, and wherein lecithin is soybean lecithin and hydrogenated soy phosphatidyl choline, egg
Yellow lecithin or phosphatidylcholine；
In b, -10 ml of phosphate buffer 1 of the pH 6.8-7.4 that the solution of step a is added to 60 DEG C of constant temperature, in temperature
Magnetic agitation 1h under 40-60 DEG C of water bath condition, removes ethanol, then ultrasonic 150 times with 400 W ultrasonic cell disruptes instrument probes, obtains
To saussurea intybus total sesquiterpene extract conventional liposome；
C, the conventional liposome for obtaining step b are injected into the Fe of 2% Tween 80 by the syringe needle with fine pore or pipeline3O4Magnetic
In property nanoparticle suspension, injection rate is 1-3mL/min, constant temperature oscillation, 30 min of water-bath after liposome completion of dropping, quiet
Separated after putting absorption 20-40 min, lyophilization obtains the magnetic liposome nanoparticle that particle diameter is 30-150nm.
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| CN102846551A (en) * | 2011-06-28 | 2013-01-02 | 复旦大学 | Liver-targeting high-density lipoprotein analogue nano-particles, preparation method thereof, and application thereof |
| CN103126990A (en) * | 2011-11-23 | 2013-06-05 | 苏州苏大赛尔免疫生物技术有限公司 | Preparation method of targeting magnetic drug loaded liposome |
| CN103127273A (en) * | 2013-03-12 | 2013-06-05 | 中国科学院新疆理化技术研究所 | Compound medicament for treating chronic liver disease and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102846551A (en) * | 2011-06-28 | 2013-01-02 | 复旦大学 | Liver-targeting high-density lipoprotein analogue nano-particles, preparation method thereof, and application thereof |
| CN103126990A (en) * | 2011-11-23 | 2013-06-05 | 苏州苏大赛尔免疫生物技术有限公司 | Preparation method of targeting magnetic drug loaded liposome |
| CN103127273A (en) * | 2013-03-12 | 2013-06-05 | 中国科学院新疆理化技术研究所 | Compound medicament for treating chronic liver disease and preparation method thereof |
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