CN103751106A - Water-soluble perfluorooctyl bromide-liposome nanosphere and preparation method thereof - Google Patents
Water-soluble perfluorooctyl bromide-liposome nanosphere and preparation method thereof Download PDFInfo
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- CN103751106A CN103751106A CN201310607899.9A CN201310607899A CN103751106A CN 103751106 A CN103751106 A CN 103751106A CN 201310607899 A CN201310607899 A CN 201310607899A CN 103751106 A CN103751106 A CN 103751106A
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Abstract
The invention relates to a water-soluble perfluorooctyl bromide-liposome nanosphere with a mean grain size of 30-800nm, the water-soluble perfluorooctyl bromide-liposome nanosphere structure is formed as follows: inner layer perfluorooctyl bromide (PFOB) is coated with outer layer lecithin bilayer to form a liposome nanosphere, the perfluorooctyl bromide-liposome nanosphere is negative in surface charge and is good in water-soluble property, an outer coating layer of the water-soluble perfluorooctyl bromide-liposome nanosphere is the well-biocompatible lecithin bilayer which can degrade in vivo, may not produce toxic and side effects on human body, the perfluorooctyl bromide-liposome nanosphere can be used as ultrasound diagnostic reagents and blood substitutes, and the particle size is easy to control and regulate, so that the application field is expanded. The preparation process of the perfluorooctyl bromide-liposome nanosphere is very simple in operation and low in requirement on equipment, and can be used for continuous production.
Description
Technical field
The present invention relates to a kind of perfluoro bromide octane-liposome nanosphere, particularly relate to a kind of water solublity perfluoro bromide octane-liposome nanosphere and preparation method thereof.
Background technology
Perfluorocarbon compound is a class ring-type or the straight chain shape organic compound that form after hydrogen atom in Hydrocarbon is all replaced by fluorine atom, due to carbon atom and fluorine atom pretend and exert oneself, fluorocarbons has extraordinary stability.Perfluorocarbon compound is water insoluble, has the function of good dissolving non-polar gas, can be used as the carrier of oxygen and carbon dioxide.Perfluorocarbon compound biochemistry inertia, mainly eliminates with breath in body.Due to its ability that has good dissolving or discharge oxygen, fluorocarbons has been employed with the partial liquid ventilation take fluorine carbon solution as gas exchange medium and has treated neonate acute respiratory distress syndrome and blood substitute.In organism, the fluorocarbons of application requires its particle diameter to be about 200 nanometers or less, this is because the larger fluorocarbons of particle diameter can not be even with aqueous solution in body, can not be stable be suspended in solution, and the solution that fluorocarbon nano ball is made, the fluorocarbons oxygen exchange area disperseing is very large, more can play the oxygen effect of taking.
Perfluoro bromide octane is the one of perfluorocarbon compound, is eight carbochains, and eight carbon atoms are except having endways a bromine atoms, and all the other positions are all connecting fluorine atom, and its molecular weight is 498.96, and boiling point is 141 ℃.Perfluoro bromide octane be applied to up to now breathing gas dissolubility maximum in biomedical all perfluorocarbon compounds chain fluorocarbons.Typical Representative is the Oxygent of U.S. combination medicine company exploitation.Perfluoro bromide octane is also good contrast agent simultaneously.The people such as Lanza have developed the PFOB excusing from death contrast agent of lipid coating the earliest, and the PFOB microsphere of gathering has the sound reflecting phenomenon of obvious enhancing.Because PFOB is not penetrated by X ray, inanimate object activity, so also can be simultaneously as CT contrast agent.
Lecithin is the one group of filemot oil material being present among animal vegetable tissue and yolk, its constituent comprises phosphoric acid, choline, fatty acid, glycerol, glycolipid, triglyceride and phospholipid, the external source of providing choline is provided, regulate serum lipids, suppress cyst fibre modification, effectively reduce the effect such as sickness rate of cholesterol, hyperlipidemia and coronary heart disease.PFOB is wrapped to form to liposome nanosphere with lecithin, can effectively controls the volatilization of PFOB, its distinctive small size has stronger tissue penetration ability, more easily through the blood vessel endothelium gap expanding in morbid state.PFOB nano-lipid ball be the one that obtains by micro-liquefaction technology of PFOB and lipid to pressure, air exposure, the metastable Emulsions such as hot river shear stress.Traditional PFOB nano-lipid ball needs a large amount of machine works, and products therefrom is generally non-water-soluble.Non-water-soluble PFOB Emulsion can a large amount of gatherings rest on liver, in the internal organs such as spleen, it is caused to toxic damages.Verified, inject in some cases perfluorocarbon compound Emulsion, liver spleen occurs that one crosses property weightening finish, and with the change of cytochrome P-450.
Therefore, prepare water miscible PFOB liposome to solving the time of staying in body, toxicity in vivo problem has great significance.
Summary of the invention
In order to overcome the deficiencies in the prior art, the invention provides a kind of water solublity perfluoro bromide octane-liposome nanosphere and preparation method thereof,
A kind of water solublity perfluoro bromide octane-liposome nanosphere, it is characterized in that, the Average Particle Diameters 30-800nm of this perfluoro bromide octane-liposome nanosphere, structure is the liposome nanosphere that outer lecithin double wrapped internal layer perfluoro bromide octane (PFOB) forms, this perfluoro bromide octane-liposome nanosphere has surperficial negative electricity, and good water solublity, its structural formula is:
A preparation method for water solublity perfluoro bromide octane-liposome nanosphere, is characterized in that, concrete steps are:
(1) get lecithin 0.01-1 gram, PFOB 10-100 μ L, is fully dissolved in organic solvent, obtains solution A;
(2) A solution is mixed with surfactant solution 5-100 milliliter, ultrasonic dispersion 1-10 minute, magnetic agitation or rotary evaporation, remove organic solvent, obtains solution B;
(3) pack solution B into bag filter, with deionized water dialysis purification in 3-5 days, or centrifugal purification, then by sample lyophilizing, obtain water solublity perfluoro bromide octane-liposome nanosphere.
Described surfactant is sodium cholate or NaTDC.
Described organic solvent is dichloromethane or chloroform.
The size of described perfluoro bromide octane-liposome nanosphere is controlled by time and the voltage of supersound process.
Prepared perfluoro bromide octane-liposome nanosphere can solve the size problem of existing fluorocarbons, by adding ionic surfactant to carry out emulsifying, obtain first water miscible perfluoro bromide octane-liposome nanosphere, improve greatly its bioavailability and safety in vivo, and widened its range of application.
Advantage of the present invention is: the preparation method that a kind of perfluoro bromide octane-liposome nanosphere is provided, adopt the good lecithin of biocompatibility as outer lapping, adopt sodium cholate or NaTDC plasma type surfactant to carry out emulsifying, obtain first the good perfluoro bromide octane-liposome of the water solublity nanosphere that surface has negative charge, human body is produced to toxic and side effects little, greatly improved clinical value and range of application; Particle diameter, at 30-800nm, is preserved stability inferior better for a long time, and this method technique is very simple, easy to operate, low for equipment requirements, can produce continuously.
Accompanying drawing explanation
Fig. 1 is the perfluoro bromide octane-liposome nanosphere scanning electron microscope (SEM) photograph obtaining in the embodiment of the present invention 1.
Fig. 2 is the perfluoro bromide octane-liposome nanosphere bromo element scattergram obtaining in the embodiment of the present invention 1.
From Fig. 1, Fig. 2, can know and find out that in perfluoro bromide octane-liposome nanosphere, bromo element distribution distributes and is consistent with nanosphere in scanning electron microscope, show to have a large amount of perfluoro bromide octanes to be wrapped in nanosphere.
Fig. 3 is the scanning electron microscope (SEM) photograph of the perfluorocarbon compound liposome nanosphere obtaining in the embodiment of the present invention 2, from scheming, can know and find out that perfluoro bromide octane-liposome nanosphere is spherical, be nucleocapsid structure, wherein stratum nucleare is thicker, shell is thinner, and perfluorocarbon compound nanosphere particle diameter is in 100 nanometer left and right.
Fig. 4 is the transmission electron microscope picture of the perfluorocarbon compound liposome nanosphere obtaining in the embodiment of the present invention 2, as can be seen from the figure perfluoro bromide octane-liposome nanosphere is spherical, be nucleocapsid structure, wherein stratum nucleare is thicker, shell is thinner, perfluorocarbon compound nanosphere particle diameter, in 100 nanometer left and right, is consistent with scanning electron microscope result.
specific implementation method
Embodiment 1:
1, get lecithin 0.1g, PFOB 60 μ L, are fully dissolved in dichloromethane, obtain solution A;
2, in A solution, add 1.5% deoxycholic acid sodium solution 20ml, ultrasonic dispersion 2min, magnetic agitation 3 hours, obtains solution B;
3, by centrifugal solution B 10000rpm, 5min, abandons supernatant, adds deionized water fully to disperse precipitation, room temperature preservation.
Embodiment 2:
1, get lecithin 0.1g, PFOB 60 μ L, are fully dissolved in dichloromethane, obtain solution A;
2, in A solution, add 1.5% deoxycholic acid sodium solution 20ml, ultrasonic dispersion 5min, magnetic agitation 3 hours, obtains solution B;
3, by centrifugal solution B 10000rpm, 5min, abandons supernatant, adds deionized water fully to disperse precipitation, room temperature preservation.
Embodiment 3:
1, get lecithin 0.1g, PFOB 60 μ L, are fully dissolved in dichloromethane, obtain solution A;
2, in A solution, add 1.5% deoxycholic acid sodium solution 20ml, ultrasonic dispersion 10 min, magnetic agitation 3 hours, obtains solution B;
3, by centrifugal solution B 10000rpm, 5min, abandons supernatant, adds deionized water fully to disperse precipitation, room temperature preservation.
Embodiment 4:
1, get lecithin 0.2g, PFOB 60 μ L, are fully dissolved in dichloromethane, obtain solution A;
2, in A solution, add 1.5% deoxycholic acid sodium solution 20ml, ultrasonic dispersion 5min, magnetic agitation 3 hours, obtains solution B;
3, pack solution B into bag filter, with deionized water dialysis 5 days, then, by sample lyophilizing, obtain final products.
Embodiment 5:
1, get lecithin 0.5g, PFOB 60 μ L, are fully dissolved in dichloromethane, obtain solution A;
2, in A solution, add 1.5% deoxycholic acid sodium solution 20ml, ultrasonic dispersion 5min, magnetic agitation 3 hours, obtains solution B;
3, pack solution B into bag filter, with deionized water dialysis 5 days, then, by sample lyophilizing, obtain final products.
Embodiment 6:
1, get lecithin 0.1g, PFOB 60 μ L, are fully dissolved in chloroform, obtain solution A;
2, in A solution, add 1.5% deoxycholic acid sodium solution 20ml, ultrasonic dispersion 5min, magnetic agitation 3 hours, obtains solution B
3, pack solution B into bag filter, with deionized water dialysis 5 days, then, by sample lyophilizing, obtain final products.
Claims (5)
1. water solublity perfluoro bromide octane-liposome nanosphere, it is characterized in that, the Average Particle Diameters 30-800nm of this perfluoro bromide octane-liposome nanosphere, structure is the liposome nanosphere that outer lecithin double wrapped internal layer perfluoro bromide octane (PFOB) forms, this perfluoro bromide octane-liposome nanosphere has surperficial negative electricity, and its structural formula is:
2. a kind of preparation method of water solublity perfluoro bromide octane-liposome nanosphere according to claim 1, is characterized in that, concrete steps are:
(1) get lecithin 0.01-1 gram, PFOB 10-100 μ L, is fully dissolved in organic solvent, obtains solution A;
(2) A solution is mixed with surfactant solution 5-100 milliliter, ultrasonic dispersion 1-10 minute, magnetic agitation or rotary evaporation, remove organic solvent, obtains solution B;
(3) pack solution B into bag filter, with deionized water dialysis purification in 3-5 days, or centrifugal purification, then by sample lyophilizing, obtain water solublity perfluoro bromide octane-liposome nanosphere.
3. a kind of preparation method of water solublity perfluoro bromide octane-liposome nanosphere according to claim 2, is characterized in that, described surfactant is sodium cholate or NaTDC.
4. a kind of preparation method of water solublity perfluoro bromide octane-liposome nanosphere according to claim 2, is characterized in that, described organic solvent is dichloromethane or chloroform.
5. a kind of preparation method of water solublity perfluoro bromide octane-liposome nanosphere according to claim 2, is characterized in that, the size of described perfluoro bromide octane-liposome nanosphere is controlled by time and the voltage of supersound process.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104623698A (en) * | 2015-02-13 | 2015-05-20 | 中国科学院上海硅酸盐研究所 | Liposome-based nano diagnosis and treatment agent for multimodal imaging and photothermal therapy and preparation method thereof |
| CN105343001A (en) * | 2015-11-02 | 2016-02-24 | 上海交通大学 | Oxygen-carried fluorocarbon emulsion and preparation method thereof |
| CN106821985A (en) * | 2017-02-28 | 2017-06-13 | 福州大学 | A kind of oxygen carrying of aptamers modification carries the multi-functional liposome complex of medicine |
| CN107807242A (en) * | 2017-10-16 | 2018-03-16 | 东南大学 | Selective analogue enztme structure and application based on gold nano grain class oxidizing ferment characteristic |
| CN108853520A (en) * | 2018-08-24 | 2018-11-23 | 重庆医科大学 | A kind of quick type lipid nano particle of sound, using and preparation method thereof |
| CN113101269A (en) * | 2021-04-15 | 2021-07-13 | 四川大学华西医院 | Delivery system based on nano-liposome, preparation method and application |
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| CN102973518A (en) * | 2012-12-18 | 2013-03-20 | 上海纳米技术及应用国家工程研究中心有限公司 | Perfluorocarbon compound lipidosome nanosphere and preparation method thereof |
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Patent Citations (1)
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| CN102973518A (en) * | 2012-12-18 | 2013-03-20 | 上海纳米技术及应用国家工程研究中心有限公司 | Perfluorocarbon compound lipidosome nanosphere and preparation method thereof |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104623698A (en) * | 2015-02-13 | 2015-05-20 | 中国科学院上海硅酸盐研究所 | Liposome-based nano diagnosis and treatment agent for multimodal imaging and photothermal therapy and preparation method thereof |
| CN105343001A (en) * | 2015-11-02 | 2016-02-24 | 上海交通大学 | Oxygen-carried fluorocarbon emulsion and preparation method thereof |
| CN106821985A (en) * | 2017-02-28 | 2017-06-13 | 福州大学 | A kind of oxygen carrying of aptamers modification carries the multi-functional liposome complex of medicine |
| CN106821985B (en) * | 2017-02-28 | 2020-04-10 | 福州大学 | Aptamer-modified oxygen-carrying and drug-carrying multifunctional liposome compound |
| CN107807242A (en) * | 2017-10-16 | 2018-03-16 | 东南大学 | Selective analogue enztme structure and application based on gold nano grain class oxidizing ferment characteristic |
| CN107807242B (en) * | 2017-10-16 | 2019-12-10 | 东南大学 | Selective mimic enzyme construction and application based on gold nanoparticle oxidase characteristics |
| CN108853520A (en) * | 2018-08-24 | 2018-11-23 | 重庆医科大学 | A kind of quick type lipid nano particle of sound, using and preparation method thereof |
| CN113101269A (en) * | 2021-04-15 | 2021-07-13 | 四川大学华西医院 | Delivery system based on nano-liposome, preparation method and application |
| CN113101269B (en) * | 2021-04-15 | 2022-04-29 | 四川大学华西医院 | Delivery system based on nano-liposome, preparation method and application |
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Application publication date: 20140430 |