CN101209348A - Elastic nano vesicle carrier and preparation method and application thereof - Google Patents
Elastic nano vesicle carrier and preparation method and application thereof Download PDFInfo
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- CN101209348A CN101209348A CNA2006101697649A CN200610169764A CN101209348A CN 101209348 A CN101209348 A CN 101209348A CN A2006101697649 A CNA2006101697649 A CN A2006101697649A CN 200610169764 A CN200610169764 A CN 200610169764A CN 101209348 A CN101209348 A CN 101209348A
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- nano vesicle
- elastic nano
- phospholipid
- carrier
- medicine
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Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to an elastic nano vesicle carrier capable of transporting active ingredients of a medicine to penetrate through a natural permeation barrier or pores (such as skin, mucous membrane, organs and the like), and a preparation method and application thereof. The vesicles have lipid bilayers for transporting one or more active ingredients across natural barriers. The vesicle at least comprises three dressing components of phospholipid, membrane softener and alcohol with different physicochemical properties. Typical nanovesicles are less than 200nm in diameter. The vesicle carrier containing the active pharmaceutical ingredient can be applied to injections, sprays and transdermal preparations.
Description
Technical field
The invention belongs to medical technical field, particularly can transport active constituents of medicine and see through elastic nano vesicle carrier of natural permeability barrier or hole (as skin, mucosa, organ etc.) and its production and use.
Background technology
Intact skin always is considered to the barrier of very effective protection health, but also is that drug transdermal enters intravital maximum barrier simultaneously.Conventional pharmaceutical dosage forms such as hydrogel, ointment or emulsifiable paste, and modern formulation all is to have a medicinal safety as liposome, but but can not overcome skin barrier effectively.The research of liposome has very long history, liposome basic composition is phospholipid/cholesterol/water, cholesterol has the effect of stabilized liposome, but but make liposome show rigidity characteristic, liposome is applied to studies show that of skin, liposome can only merge at keratodermatitis can not enter the skin depths, so very difficult the entering through barrier of liposome organized in depths or the blood.And German G.Cevc (Elastic vesicles astopical/transdermal drug delivery systems, M.J.Choi and H.I.MaibachInternational Journal of Cosmetic Science, 2005,27,211～221) Yan Jiukaifa carrier (Transfersome) transdermal drug delivery system has been obtained very big progress, has some medicines to enter the clinical research stage.The alcohol liposome (Ethosomes) of Israel Elka Touitou research has shown to have the good transdermal ability in addition.The elasticity lipid vesicle has unique multifarious function as effective transdermal carrier, can transport different medicines, and not need to consider its size, structure, molecular weight or polarity.The constituent of carrier generally is phospholipid/surfactant/water, and the composition of alcohol liposome is phospholipid/alcohol/water.They have identical characteristic, are exactly that the lipid bilayer flowability is higher, easily deformable transdermal barrier.
Carrier is used with the form of emulsion (lotion) in use normally at non-closed system, because its transdermal mechanism mainly is to depend on the aquation gradient, makes vesicle under the effect of transdermal aquation power, can self extrusion pass through the cutin interlayer region.And the aquation gradient is not obvious in closed system, so carrier is difficult to see through skin.Usually contain 20～50% ethanol in the alcohol liposome,, can make bilayer have deformability owing to there is high-load ethanol.Alcohol liposome can make the horny layer membrane fluidity increase simultaneously, thereby has increased percutaneous permeation.Alcohol liposome is made into paster usually and uses at closed system, and the effect of using at closed system is better than non-closed system.
In the present invention, we have prepared a kind of novel elastic nano vesicle carrier that contains phospholipid/film softening agent/alcohol/water, combine the characteristics of carrier and alcohol liposome, this elastic nano vesicle carrier all has fabulous percutaneous penetration power at closed system and non-closed system, can shortly ooze with the auxiliary short infiltration method of physics such as the short saturating method of iontophoresis, electroporation, laser pore, radio frequency, heat is short oozes and the micropin pore is share, and further improves percutaneous permeation.
Summary of the invention
One of purpose of the present invention is to provide the elastic nano vesicle carrier that can transport active constituents of medicine, and the diameter of this elastic nano vesicle is at 30～500nm, and preferred especially diameter is at 50～200nm.
Two of purpose of the present invention is to provide the elastic nano vesicle preparations that contains active constituents of medicine, and the diameter of this elastic nano vesicle is at 30～500nm, and preferred especially diameter is at 50～200nm.
Three of purpose of the present invention is to provide the preparation method of elastic nano vesicle carrier.
Four of purpose of the present invention is to provide the preparation method of the elastic nano vesicle preparations that contains active constituents of medicine.
Five of purpose of the present invention is to provide the purposes of elastic nano vesicle carrier.
Elastic nano vesicle carrier of the present invention can be transported active constituents of medicine, and the composition of this elastic nano vesicle carrier contains different dressing composition and suspension medias on phospholipid, film softening agent, three kinds of physicochemical properties of alcohol at least; Wherein, the content of phospholipid is 5wt%～15wt%, the content of film softening agent is 0.5wt%～3wt%, alcohol content is 5wt%～40wt%, and all the other are suspension media mixed solutions of remaining various compositions behind phospholipid, film softening agent, alcohol and water or phosphate buffer (pH 5～7.5) the mixing formation elastic nano vesicle.
Elastic nano vesicle carrier provided by the invention can be transported active constituents of medicine, can transport one or more active constituents of medicine, the active constituents of medicine total content is 0.01wt%～10wt%, and the total content of preferred agents active component is 0.05wt%～2wt%.
Elastic nano vesicle of the present invention has lipid bilayer, both the film of one deck or which floor phospholipid bilayer composition.(the single or multiple lift lipid bilayer is the film of the different layers that forms of the difference according to constituent content, what granule was big usually is multilayer film, less than 100nm be monofilm, lipid bilayer be because phospholipid have amphiphilic, from aqueous solution, forming difform bilayer structure).
The diameter of described elastic nano vesicle is at 30～500nm, and preferred especially diameter is at 50～200nm.
The elastic nano vesicle carrier of producing can remove by filtering method and degerm, and can utilize filtering method to measure the elasticity of vesicle.The aperture of the filter of antibacterial is less than 220nm, measures the preferred 30～100nm in aperture of the elastic filter of vesicle.
If the system of elastic nano vesicle carrier is relatively more responsive to air or oxygen, can be with this vesicle carrier stored under refrigeration, for example 4 degree also can (as nitrogen) prepare and store under the environment of noble gas simultaneously.
In order to increase the stability of elastic nano vesicle carrier, can add antioxidant and/or stabilizing agent (having part antioxidant and/or stabilizing agent to be wrapped in the elastic nano vesicle) in preparation method, wherein antioxidant and/or the stabilizing agent content in carrier is less than 3wt%.Antioxidant such as vitamin E, ascorbic acid, esterification ascorbic acid or their any mixture etc.; Stabilizing agent such as phenol, phenyl methylcarbamate or their mixture etc.Elastic nano vesicle carrier can also be dispersed in medical aquogel, the emulsifiable paste, enhanced stability in the emulsion, can also be made into paster and use.
Elastic nano vesicle carrier provided by the invention and contain in the preparation method of active constituents of medicine elastic nano vesicle and do not contain poisonous deleterious organic solvent is as chloroform, methanol etc.In preparation process, phospholipid utilizes the alcohol dissolving with the active constituents of medicine that is insoluble in water, and film softening agent and other composition soluble in water (comprising active constituents of medicine soluble in water) utilize water or phosphate buffer to dissolve.Two kinds of different components are mixed, produce elastic nano vesicle.Mixing can be preparation methoies such as mechanical agitation, shearing, pulverizing, ultrasonic, injection, high-pressure extrusion.Usually preparation is at room temperature carried out, preparation temperature 0～60 degree all can, be preferably in below the room temperature for the unstable temperature active component and carry out.
Composition soluble in water: dissolubility is greater than the weight percent concentration of this composition in the prescription.
The preparation method of elastic nano vesicle carrier of the present invention may further comprise the steps:
(1). take by weighing phospholipid,, remove ethanol with Rotary Evaporators or logical nitrogen with the adequate amount of ethanol dissolving;
(2). with film softening agent water or phosphate buffer (pH 5～7.5) dissolving;
(3). the product that step (2) is obtained is removed alcoholic acid phospholipid with step (1) and is mixed, add alcohol, mix, further homogenate (dispersing emulsification machine) or ultrasonic, obtain being suspended in the elasticity vesicle in the suspension media, wherein, suspension media is the mixed solution of remaining various compositions behind phospholipid, film softening agent, alcohol and water or phosphate buffer (pH 5～7.5) the mixing formation elastic nano vesicle, the content of phospholipid is 5wt%～15wt%, the content of film softening agent is 0.5wt%～3wt%, and pure content is 5wt%～40wt%.The vesicle diameter is 30～500nm;
(4). the elastic nano vesicle carrier that step (3) is obtained removes by filter impurity and antibacterial, tinning.Can use the 450nm filter membrane to remove impurity earlier, re-use, also can directly use the removal of impurity of 220nm filter membrane and antibacterial less than the degerming of 220nm filter membrane.
Temperature is no more than 60 degree in the aforesaid operations process.
In above-mentioned preparation process, when step (1) dissolving phospholipid, or when step (2) dissolving film softening agent, can add the active constituents of medicine that accounts for elastic nano vesicle carrier 0.01wt%～10wt%.
In above-mentioned preparation process, when step (1) dissolving phospholipid, can add antioxidant and/or stabilizing agent, wherein antioxidant and/or the stabilizing agent content in carrier preferably accounts for elastic nano vesicle carrier 0.01～3wt% less than 3wt%.
Also can be for active constituents of medicine soluble in water (dissolubility greater than prescription in concentration expressed in percentage by weight) without dissolve with ethanol, but and the film softening agent mix with phospholipid again after water or the phosphate buffer dissolving together.
In above-mentioned preparation, the vesicle carrier that final filtration obtains can further be dispersed in medical aquogel, emulsifiable paste or the emulsion or be made into paster and use.
The present invention has prepared a kind of novel elastic nano vesicle carrier that contains phospholipid/film softening agent/alcohol/water, combine the characteristics of carrier and alcohol liposome, this elastic nano vesicle carrier all has fabulous percutaneous penetration power at closed system and non-closed system, can share with physics auxiliary short infiltration skin method such as the short saturating method of iontophoresis, electroporation, ultrasonic and micropin pore, further improve percutaneous permeation.The vesicle carrier that contains active constituents of medicine can be applied to injection, spray and preparation capable of permeating skin.
Definition
Phospholipid, the phosphorated lipid material of phospholipid., kind is a lot of, is playing an important role aspect the structure of living cells and the metabolism.The phospholipid of Shi Yonging can be natural in the present invention, also can be synthetic, can be that saturated series, unsaturated series, symmetric form, asymmetric, PEG are in conjunction with phospholipid, phospholipid in conjunction with cancerous cell targeting functional group transferrins (transferrin), phospholipid in conjunction with folic acid target administration group, in conjunction with the phospholipid of polysaccharide etc., contain polarity part and nonpolar part in its basic molecular structure.The long hydrocarbon chain (R1 and R2) of two fatty acids is contained in the nonpolar portion of molecule, and the long hydrocarbon chain of described R1 and R2 can be symmetric, asymmetrical, saturated, unsaturated, and chain length is at C
10To C
20The polarity part is made up of phosphatidyl and terminal unit X, and phospholipid can be classified according to the difference of polar head.As shown in the formula expression.
Y is H, Na or NH
4
For example, X=H constitutes the simplest phosphatidic acid; X is 2-trimethylamine groups ethyl (a choline base), is called phosphatidylcholine (main component of lecithin).Other are as phosphatidyl glycerol, phosphatidyl oil, PHOSPHATIDYL ETHANOLAMINE (cephalin main component), phosphatidylinositols, Phosphatidylserine, polyene phosphatidylcholine, phosphatidyl PEG derivant, the phosphatidyl folic acid derivatives, phosphatidyl transferrins derivant, the phosphatidyl antibody derivatives, phosphatidyl polysaccharide derivates or phosphatidyl polypeptide derivative etc.
Film softening agent: as sodium cholate, sodium deoxycholate, oleic acid, Palmic acid, glycyrrhizic acid dipotassium or soil temperature 80.
Alcohol: ethanol, ethylene glycol, propanol, propylene glycol, glycerol, isopropyl alcohol, butanediol, two propyleneglycoles or their any mixture.
Active constituents of medicine: the composition of most of different activities is suitable for this elastic nano vesicle carrier, and active constituents of medicine can be the composition of water miscible and/or slightly water-soluble.Can be natural extract, chemosynthesis composition, biological preparation, and not be subjected to the molecule quantitative limitation.This active constituents of medicine is selected from one or more the mixture that contains in treatment tumor disease composition such as paclitaxel and derivant thereof, amycin, cisplatin, bleomycin, 5-fluorouracil, the interferon medicine series; Or be selected from and contain vindesine, interleukin-2, vincaleucoblastine, vincristine, dactinomycin, fotemustine, ifosfamide, lomustine, carmustine, dacarbazine or carboplatin medicine administered by injection thing; Maybe can be selected from the medicine of compositions such as containing anesthetis, analgesic, anti-cardiovascular disease, antidiabetic medicine, anticoagulant, resisting hypertension, hypotension, vertigo or resisting emesis, anti-inflammatory, asthma, gynaecopathia or birth control.
Description of drawings
Fig. 1. the transmission electron microscope photo of sample 2 in the embodiment of the invention 3～4.Mean diameter is 76nm.
Fig. 2. the in-vitro percutaneous permeability curve of vincristine vesicle patch formulation (Corium Mus) in the embodiment of the invention 13.
The specific embodiment
Further specify content of the present invention below in conjunction with embodiment, but be not limited to this.Except as otherwise noted, ratio is meant weight ratio, and percent is meant percetage by weight, and percentage ratio is meant the ratio that accounts for cumulative volume, and particle size determination is at room temperature to carry out.
Embodiment 1 elastic nano vesicle carrier
With an amount of dissolve with ethanol of soybean lecithin, vitamin E, behind the mix homogeneously, logical nitrogen makes the ethanol volatilization, add sodium cholate and a certain amount of 5mM phosphate buffer pH 6.5 then, and add hexylene glycol, stirring at room 1 hour, water-bath is ultrasonic 30 minutes then, obtains elastic nano vesicle.This elastic nano vesicle is suspended in the mixed solution that mentioned component mix to form remaining various compositions behind the vesicle.Wherein, the content of soybean lecithin is 5.6%, and the content of sodium cholate is 1%, and the content of vitamin E is 0.1%, and the content of hexylene glycol is 15%.Measuring particle diameter with the laser particle size light scattering apparatus is 61nm.
Embodiment 2 elastic nano vesicle carriers
With an amount of dissolve with ethanol of soybean lecithin, phenol, behind the mix homogeneously, logical nitrogen makes the ethanol volatilization, add glycyrrhizic acid dipotassium and a certain amount of 5mM phosphate buffer pH 6.5 then, and add isopropyl alcohol and alcoholic acid mixed liquor, wherein isopropyl alcohol and alcoholic acid weight ratio are 6: 4, stirring at room 1 hour, homogenate obtains elastic nano vesicle.This elastic nano vesicle is suspended in the mixed solution that mentioned component mix to form remaining various compositions behind the vesicle.Wherein, the content of soybean lecithin is 10%, and the content of phenol is 0.1%, and the content of glycyrrhizic acid dipotassium is 2%, and isopropyl alcohol and alcoholic acid total content are 15%.Measuring particle diameter with the laser particle size light scattering apparatus is 230nm.
Embodiment 3～4
With an amount of dissolve with ethanol of soybean lecithin, paclitaxel, vitamin E, behind the mix homogeneously, rotary evaporation removes ethanol, add sodium cholate and a certain amount of 5mM phosphate buffer pH 6.5 then, and add quantitative ethanol, stirring at room 1 hour, water-bath is ultrasonic 30 minutes then, obtains elastic nano vesicle.This elastic nano vesicle is suspended in the mixed solution that mentioned component mix to form remaining various compositions behind the vesicle.Wherein, the content of soybean lecithin is 5%, and sodium cholate content is as shown in table 1, and the content of paclitaxel is 1%, and the content of vitamin E is 0.2%, and alcoholic acid content is 10%.
With Sephadex G-50 gel separation free drug and vesicle, use HPLC detection envelop rate (detect wavelength 230nm, flow velocity 1ml/min, mobile phase is second cyanogen: ultra-pure water=65: 35[V: V]), particle diameter measured with the laser particle size light scattering apparatus.The transmission electron microscope photo of sample 2 as shown in Figure 1.Mean diameter is 76nm.
Table 1 soybean lecithin and sodium cholate content
The envelop rate of table 2 sample 1～2 and vesicle particle diameter
| The sample sequence number | Envelop rate | Vesicle particle diameter nm |
| 1 | 73.3％ | 72 |
| 2 | 67.0％ | 76 |
Embodiment 5
With soybean lecithin (phosphatidylcholine＞92%), estradiol (estrogen, the treatment gynaecopathia) uses an amount of dissolve with ethanol, behind the mix homogeneously, logical nitrogen makes the ethanol volatilization, add sodium cholate and a certain amount of 5mM phosphate buffer pH 6.5 then, and add butanediol, stirring at room 1 hour, homogenate 3 times obtains elastic nano vesicle.This elastic nano vesicle is suspended in the mixed solution that mentioned component mix to form remaining various compositions behind the vesicle.Wherein, the content of soybean lecithin is 5%, and estradiol content is 0.2%, and the content of sodium cholate is 1%, and the content of butanediol is 15%.
With Sephadex G-50 gel separation free drug and vesicle, use HPLC to detect envelop rate, measure particle diameter with the laser particle size light scattering apparatus.Envelop rate 83%, vesicle particle diameter are 92nm.
Embodiment 6～8
With an amount of dissolve with ethanol of soybean lecithin, enoxolone, rotary evaporation is removed ethanol behind the mix homogeneously, adds film softening agent (as table 5) and a certain amount of 5mM phosphate buffer pH 6.5 then, and adding ethanol, stirring at room 1 hour, water-bath is ultrasonic 30 minutes then, obtains elastic nano vesicle.This elastic nano vesicle is suspended in the mixed solution that mentioned component mix to form remaining various compositions behind the vesicle.Wherein, the content of soybean lecithin is 8%, and the content of film softening agent is 1.5%, and the content of enoxolone is 0.1%, and alcoholic acid content is 10%.
With Sephadex G-50 gel separation free drug and vesicle, use HPLC to detect envelop rate, measure particle diameter with the laser particle size light scattering apparatus.
Table 5 film softening agent kind
| The sample sequence number | The film softening agent |
| 1 | Sodium deoxycholate |
| 2 | Oleic acid |
| 3 | Glycyrrhizic acid dipotassium |
The envelop rate of table 6 sample 1～3 and particle diameter
| The sample sequence number | Envelop rate | Particle diameter nm |
| 1 | 76 | 83 |
| 2 | 71 | 161 |
| 3 | 70 | 89 |
Embodiment 9～12
With an amount of dissolve with ethanol of hydrogenated soy phosphatidyl choline, sodium deoxycholate, paclitaxel, add ethanol and stir ultrasonic dissolution, rotary evaporation is removed ethanol, add ethanol and a certain amount of 5mM phosphate buffer pH6.5 then, stirring at room aquation 30 minutes, the ultrasonic certain hour of water-bath, ultrasonic temperature are controlled at 12～18 ℃.Obtain elastic nano vesicle.This elastic nano vesicle is suspended in the mixed solution that mentioned component mix to form remaining various compositions behind the vesicle.Wherein, the content of hydrogenated soy phosphatidyl choline is 8.5%, and content of taxol is 0.2%, and the content of sodium deoxycholate is 1.5%, and alcoholic acid content is 10%.
The microscopic examination of the suspension that obtains:
Sample 1: ultrasonic 10 minutes, muddiness;
Sample 2: ultrasonic 20 minutes, slight haze;
Sample 3: ultrasonic 30 minutes, translucent suspension;
Sample 4: ultrasonic 60 minutes, translucent suspension.
Embodiment 13
With phosphatidyl PEG (2000), sodium deoxycholate, an amount of dissolve with ethanol of vincristine, add ethanol and stir ultrasonic dissolution, rotary evaporation is removed ethanol, add 1 then, 3-butanediol and a certain amount of 5mM phosphate buffer pH 6.5, ultrasonic mixing 30 minutes is spared 3 times with high pressure dispersing emulsification machine breast, with degerming of 200nm membrane filtration and impurity, obtain elastic nano vesicle.This elastic nano vesicle is suspended in the mixed solution that mentioned component mix to form remaining various compositions behind the vesicle.Wherein, the content of phosphatidyl PEG (2000) is 8%, and vincristine content is 0.2%, and the content of sodium deoxycholate is 1.5%, and the content of 1,3 butylene glycol is 10%.With polyvinylpyrrolidone-acetate ethylene copolymer (PVP-VA), abietic resin, 2.5% lecithin, 15%1,3-butanediol mix homogeneously adds that the vesicle uniform mixing is evenly coated on the backing (Backing), makes paster.As shown in Figure 2, the in-vitro percutaneous permeability curve of vincristine vesicle patch formulation (Corium Mus) shows that this paster and micropin percutaneous plaster unite use, has further improved percutaneous permeation.
Have pin to handle: skin surface was handled with the micropin percutaneous plaster, 121 of micropin numbers, 150 microns of height.
Needleless is handled: the complete Corium Mus that does not pass through special handling.
Claims (16)
1. elastic nano vesicle carrier, it is characterized in that: this elastic nano vesicle carrier can be transported active constituents of medicine; The composition of this elastic nano vesicle carrier contains phospholipid, film softening agent, three kinds of dressing compositions of alcohol and suspension media at least; Wherein, the content of phospholipid is 5wt%～15wt%, the content of film softening agent is 0.5wt%～3wt%, the content of alcohol is 5wt%～40wt%, and all the other are suspension media mixed solutions of remaining various compositions behind phospholipid, film softening agent, alcohol and water or the phosphate buffer mixing formation elastic nano vesicle.
2. elastic nano vesicle carrier according to claim 1 is characterized in that: contain active constituents of medicine in the described elastic nano vesicle carrier, wherein the total content of active constituents of medicine in carrier is 0.01wt%～10wt%.
3. elastic nano vesicle carrier according to claim 1 and 2 is characterized in that: contain antioxidant and/or stabilizing agent in the described elastic nano vesicle carrier, wherein antioxidant and/or the stabilizing agent content in carrier is less than 3wt%;
Described antioxidant is vitamin E, ascorbic acid, esterification ascorbic acid or their any mixture;
Described stabilizing agent is phenol, phenyl methylcarbamate or their mixture.
4. elastic nano vesicle carrier according to claim 1 and 2 is characterized in that: described elastic nano vesicle has the film of one deck or which floor phospholipid bilayer composition.
5. elastic nano vesicle carrier according to claim 3 is characterized in that: described elastic nano vesicle has the film of one deck or which floor phospholipid bilayer composition.
6. according to claim 1,2 or 5 described elastic nano vesicle carriers, it is characterized in that: the diameter of described elastic nano vesicle is at 30～500nm.
7. elastic nano vesicle carrier according to claim 4 is characterized in that: the diameter of described elastic nano vesicle is at 30～500nm.
8. elastic nano vesicle carrier according to claim 1 or 5, it is characterized in that: contain polarity part and nonpolar part in the basic molecular structure of described phospholipid, the long hydrocarbon chain of two fatty acids is contained in the nonpolar portion of molecule, this long hydrocarbon chain is symmetric, asymmetrical, saturated, unsaturated, chain length is at C
10To C
20The polarity part is made up of phosphatidyl and terminal unit.
9. elastic nano vesicle carrier according to claim 8 is characterized in that: described phospholipid is phosphatidic acid, phosphatidylcholine, phosphatidyl glycerol, phosphatidyl oil, PHOSPHATIDYL ETHANOLAMINE, phosphatidylinositols, Phosphatidylserine, polyene phosphatidylcholine, phosphatidyl PEG derivant, phosphatidyl folic acid derivatives, phosphatidyl transferrins derivant, phosphatidyl antibody derivatives, phosphatidyl polysaccharide derivates or phosphatidyl polypeptide derivative.
10. elastic nano vesicle carrier according to claim 1 is characterized in that: described film softening agent is sodium cholate, sodium deoxycholate, oleic acid, Palmic acid, glycyrrhizic acid dipotassium or soil temperature 80.
11. elastic nano vesicle carrier according to claim 1 is characterized in that: described alcohol is ethanol, ethylene glycol, propanol, propylene glycol, glycerol, isopropyl alcohol, butanediol, two propyleneglycoles or their any mixture.
12. elastic nano vesicle carrier according to claim 1 and 2 is characterized in that: described active constituents of medicine is selected from one or more the mixture in the paclitaxel that contains treatment tumor disease composition and derivant thereof, amycin, cisplatin, bleomycin, 5-fluorouracil, the interferon medicine series; Or be selected from and contain vindesine, interleukin-2, vincaleucoblastine, vincristine, dactinomycin, fotemustine, ifosfamide, lomustine, carmustine, dacarbazine or carboplatin medicine administered by injection thing; Or be selected from the medicine that contains anesthetis, analgesic, anti-cardiovascular disease, antidiabetic medicine, anticoagulant, resisting hypertension, hypotension or resisting emesis, asthma, gynaecopathia or antifertility composition.
13. the preparation method according to each described elastic nano vesicle carrier of claim 1～12 is characterized in that, this method may further comprise the steps:
(1). take by weighing phospholipid, use dissolve with ethanol, remove ethanol with Rotary Evaporators or logical nitrogen;
(2). with film softening agent water or phosphate buffer dissolving;
(3). the product that step (2) is obtained is removed alcoholic acid phospholipid with step (1) and is mixed, add alcohol, mix, further homogenate or ultrasonic obtains being suspended in the elasticity vesicle in the suspension media, wherein, suspension media is the mixed solution of remaining various compositions behind phospholipid, film softening agent, alcohol and water solution or the phosphate buffer mixing formation elastic nano vesicle, the content of phospholipid is 5wt%～15wt%, and the content of film softening agent is 0.5wt%～3wt%, and pure content is 5wt%～40wt%.
14. method according to claim 13 is characterized in that: when step (1) dissolving phospholipid, or when step (2) dissolving film softening agent, add the active constituents of medicine that accounts for elastic nano vesicle carrier 0.01wt%～10wt%.
15. according to claim 13 or 14 described methods, it is characterized in that: add antioxidant and/or stabilizing agent when step (1) dissolving phospholipid, wherein antioxidant and/or the stabilizing agent content in carrier is less than 3wt%.
16. purposes according to each described elastic nano vesicle carrier of claim 1～12, it is characterized in that: in elastic nano vesicle carrier, add active constituents of medicine, obtain containing the elastic nano vesicle carrier preparation of active constituents of medicine and the method for the auxiliary short infiltration skin of physics and unite use, to improve percutaneous permeation;
The method of the auxiliary short infiltration of described physics skin comprises that iontophoresis urge that saturating method, electroporation, laser pore, radio frequency are shortly oozed, heat is urged to ooze, micropin pore and ultrasonic introductory technique.
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