CN108553422A - A kind of novel nano drug and preparation method thereof - Google Patents
A kind of novel nano drug and preparation method thereof Download PDFInfo
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Abstract
A kind of novel nano drug of present invention offer and preparation method thereof, the Nano medication is the nano-particle obtained by hydrophobic drug and indocyanine green self assembly.
Description
Technical field
The invention belongs to medicament nano technical field, be related to it is a kind of have high dispersion, stability, size tunable,
It is the novel nano drug and its system that Food and Drug Adminstration of the US (FDA) ratifies drug without additional carrier, each component
Preparation Method.
Background technology
In order to solve, the small molecule tumor therapeutic agent especially hydrophobic drug body-internal-circulation period is short, tumor-targeting
Defect that is low, being easy to damage normal cell, vast researcher devises diversified drug delivery system, by small molecule
Medicine is encapsulated into inside the nano-carrier particle with biocompatibility, to realize long circulating period, actively or passively
Targeting and controlled drug release.Such as the mesoporous SiO of researcher's discovery MCM-41 types in 20012With efficient medicament storage and
Sustained release performance (Chem.Mat.2001,13, (2), 308-311) and good biocompatibility.Therefore mesoporous SiO2It is good
Pharmaceutical carrier, and play in the early diagnosis and therapy of major disease unique advantage (Adv.Funct.Mater.2007,
17,(8),1225-1236)。
However prepare various drug delivery vehicles and usually require complicated synthetic schemes, include the self assembly and change of supermolecule
Modification is learned, these processes are always difficult to accurately control, and repeatability is poor, result in carrier with extremely low drugloading rate and carry drug effect
Rate limits its effect in vitro, in experiment in vivo.One or more inorganic material, gold have been used when preparing carrier simultaneously
Belong to material, high molecular material, although these materials are novel, another aspect, their interactions between medicine
It need to be furtherd investigate, if the effect of influencing drug needs to examine one by one.What is more important, carrier material may have
Cytotoxicity can damage normal organ, influence organism function, even result in death.Therefore realize drug delivery system to facing
Bed still suffers from huge challenge using conversion.
Invention content
In view of the above drug delivery vehicle there are the shortcomings that and limitation, the purpose of the present invention is to provide a kind of height point
It dissipates, size tunable, stability are good, without carrier, the collaboration of a variety of therapeutic modalities, the guaranteed Nano medication of safety and its preparation
Method.
On the one hand, the present invention provides a kind of Nano medication, the Nano medication be by hydrophobic drug and indocyanine green from
Nano-particle obtained by assembling.
According to the present invention, using between hydrophobic drug, between hydrophobic drug and indocyanine green (ICG)
Interaction, Nano medication is obtained by simple molecular self-assembling.Drug used is FDA approvals, and toxic side effect can have
Effect control, therefore wide application prospect is shown in clinical therapy of tumor field.
Preferably, the nano-particle is spherical morphology, grain size is 5~400nm.
Preferably, the hydrophobic drug is hydrophobic anticancer drug, it preferably is selected from taxol, camptothecine, Sorafenib
At least one.
Preferably, in the Nano medication, the hydrophobic drug accounts for 80% of total quality or more.
Preferably, the Nano medication does not contain other carriers.
On the other hand, the present invention provides a kind of preparation method of Nano medication, includes the following steps:
(1) hydrophobic drug is dissolved in dimethyl sulfoxide (DMSO), obtains the first solution;
(2) indocyanine green is dissolved in water or NaHCO3In aqueous solution, the second solution is obtained;
(3) the first solution is mixed with the second solution, by being self-assembly of Nano medication.
Passed through using tumor therapeutic agent all ratified by FDA, to can be used for clinical application as raw material according to the present invention
Simple self-assembly method obtained high degree of dispersion, size tunable, stability it is good, without carrier, the collaboration of a variety of therapeutic modalities, safety
The guaranteed novel nano drug of property.Synthesis technology of the present invention is simple and practicable, safety without any pollution, yield is high, only needs letter
Constructing for nanostructure can be realized in single molecular self-assembling, and at low cost, efficient, easy industrialized production has wide answer
Use foreground.
Preferably, the hydrophobic drug in the first solution and the feedstock mass of the indocyanine green in the second solution ratio are 5:1
To 1:It is adjustable between 2.
Preferably, in step (3), the first solution is added dropwise in the second solution to mix the first solution and the second solution
It closes, it is preferable that drop rate is 1~5 μ L/s.
Preferably, in step (3), the mode using stirring and/or ultrasound makes hydrophobic drug be mixed with indocyanine green
Even and then self assembly is nanostructure.
Preferably, further including separating Nano medication from mixed solution, it is preferable that carried out using the method for centrifugation
Separation.
Description of the drawings
Fig. 1 is the flow chart of the processing mode for preparing self-assembled nanometer drug of an embodiment of the present invention.
Fig. 2 is the TEM figures of the taxol-ICG self-assembled nanometer drugs synthesized in embodiment 1, is intuitively shown regular
Spherical morphology, the dispersibility of uniform grain size and height.
Fig. 3 is the TEM figures of the camptothecine-ICG self-assembled nanometer drugs synthesized in embodiment 2, is intuitively shown regular
Spherical morphology, the dispersibility of uniform grain size and height.
Fig. 4 is the TEM figures of the Sorafenib-ICG self-assembled nanometer drugs synthesized in embodiment 3, intuitively shows rule
The dispersibility of whole spherical morphology, uniform grain size and height.
Fig. 5 is that (feedstock mass is than 1 for the taxol-ICG self-assembled nanometers drug that is synthesized in embodiment 4:1) TEM figures, directly
Show regular spherical morphology, the dispersibility of uniform grain size and height with seeing.
Fig. 6 is the TEM figures of the taxol-ICG self-assembled nanometers drug (5 μ L/s of drop rate) synthesized in embodiment 5, directly
Show regular spherical morphology, the dispersibility of uniform grain size and height with seeing.
Fig. 7 is the TEM figures of taxol-ICG (water sample) the self-assembled nanometer drug synthesized in embodiment 6, is intuitively shown
Go out regular spherical morphology, the dispersibility of uniform grain size and height.
Fig. 8 is the TEM figures of camptothecine-ICG (water sample) the self-assembled nanometer drug synthesized in embodiment 7, is intuitively shown
Go out regular spherical morphology, the dispersibility of uniform grain size and height.
Fig. 9 is the TEM figures of Sorafenib-ICG (water sample) the self-assembled nanometer drug synthesized in embodiment 8, can equally be seen
Go out complete spherical morphology, uniform grain size and good dispersibility.
Figure 10 is the grain size distribution of the taxol-ICG self assembly drugs of synthesis.
Figure 11 is the grain size distribution of the camptothecine-ICG self assembly drugs of synthesis.
Figure 12 is the grain size distribution of the Sorafenib-ICG self assembly drugs of synthesis.
Figure 13 be synthesis taxol-ICG self assemblies drug (feedstock mass is than 1:1) grain size distribution.
Figure 14 is the grain size distribution of the taxol-ICG self assemblies drug (5 μ L/s of drop rate) of synthesis.
Figure 15 is the grain size distribution of taxol-ICG (water sample) self assembly drug of synthesis.
Figure 16 is the grain size distribution of camptothecine-ICG (water sample) self assembly drug of synthesis.
Figure 17 is the grain size distribution of Sorafenib-ICG (water sample) self assembly drug of synthesis.
Figure 18 is the photo of the PBS solution of taxol-ICG.It is observed that the distinctive Tyndall effect of colloid.
Figure 19 is that taxol white powder is directly dispersing in water, forms white precipitate.
Figure 20 is the photo of the PBS solution of camptothecine-ICG.It is observed that the distinctive Tyndall effect of colloid.
Figure 21 is that camptothecine white powder is directly dispersing in water, can not be dissolved, always with the presence of precipitation.
Figure 22 is the photo of the PBS solution of Sorafenib-ICG.It is observed that the distinctive Tyndall effect of colloid.
Figure 23 is that Sorafenib pale yellow powder is directly dispersing in water, can not be dissolved, always with the presence of precipitation.
Specific implementation mode
It is further illustrated the present invention below in conjunction with attached drawing and following embodiments, it should be appreciated that attached drawing and following embodiments
It is merely to illustrate the present invention, is not intended to limit the present invention.
A kind of medicine delivering new approaches are there is provided herein, i.e., the self assembly for ratifying drug by FDA prepares height point
Dissipate, size tunable, stability is good, the guaranteed novel nano drug of safety, additional carrier is not needed, to solve existing skill
The problems such as complex steps present in art, efficiency are low, repeatable poor, safety is unsecured.
It is disclosed a kind of Nano medication, the Nano medication is obtained by hydrophobic drug and indocyanine green self assembly
Nano-particle.
Self assembly (self-assembly) generally refers to basic structural unit (molecule, nano material etc.) and has spontaneously formed
A kind of technology of sequence structure.During self assembly, basic structural unit is spontaneous under the interaction based on non-covalent bond
Be formed as a stabilization, the structure with certain regular geometric appearance.Here " self assembly " refers to hydrophobic drug and Yin
The green formation preparation process for spontaneously forming spherical ordered structure of diindyl cyanines.
Hydrophobic drug is not particularly limited, preferably hydrophobic drug, more preferably hydrophobic small molecules anticancer drug,
Such as taxol, camptothecine, Sorafenib etc..
In Nano medication, the ratio of hydrophobic drug is adjustable, such as can account for 80% of total quality or more.In this way,
Drug load is big, and utilization ratio of drug is high.
Nano-particle can be spherical morphology.The grain size of nano-particle is adjustable, such as controllable in 5nm~400nm, preferably
30~100nm.Moreover, the nano-particle can be with high degree of dispersion.
It in the Nano medication, can be only made of hydrophobic drug and indocyanine green, not contain other carrier materials.
That is selecting ICG for unique auxiliary material.It is possible thereby to save cost, and avoid the risk that other carrier materials may be brought.
Indocyanine green ratifies clinical application by FDA, securely and reliably.Dewatering medicament nano may be implemented using indocyanine green
Change, and enhances the water solubility of dewatering medicament.
A kind of simple and practicable, environmental-friendly method is also disclosed herein to synthesize with high degree of dispersion, size tunable, steady
It is qualitative it is good, without carrier, a variety of therapeutic modalities collaboration, the guaranteed novel nano drug of safety.Hereinafter, as an example, saying
The preparation method of bright above-mentioned Nano medication.
Fig. 1 shows the flow chart of the processing mode for preparing self-assembled nanometer drug of an embodiment of the present invention.Such as Fig. 1 institutes
Show, first, prepare medicines solution.Specifically, hydrophobic drug is dissolved in dimethyl sulfoxide (DMSO), the first solution is obtained.It will
Indocyanine green is dissolved in water or NaHCO3In aqueous solution, the second solution is obtained.
In first solution, the concentration of hydrophobic drug can be 0.5~2g/L.
In second solution, the concentration of indocyanine green can be 0.2~1g/L.In second solution, if selecting NaHCO3Aqueous solution
As solvent, then NaHCO3In aqueous solution, NaHCO3Concentration can be 0.02~5mM.
Then, medicaments uniformity mixing is self-assembly of Nano medication.Specifically, the first solution and the second solution are mixed
It closes.The two mixed process is to be self-assembly of the process of Nano medication.
First solution is preferably added dropwise to by given pace in the second solution by hybrid mode, the mixing being added dropwise dropwise
Mode both can ensure there is the sufficient self assembly time, compared to directly quickly being more easy to the mode of the two mixing to obtain grain size
Uniform, finely dispersed Nano medication particle.By regulating and controlling drop rate, the grain size of the Nano medication of preparation can be regulated and controled.The
The drop rate of one solution is preferably 1~5 μ L/s.With the rate be added dropwise, can obtain size uniformity, monodispersity nanometer medicine
Composition granule.
The ratio of first solution and the second solution is adjustable, such as can make the hydrophobic drug in the first solution and the second solution
In indocyanine green feedstock mass ratio 5:1 to 1:It is adjustable between 2.It is mixed with the ratio, can realize drug and indoles
Under the premise of the green high usage of cyanines, the successful self assembly of the type nano granular, and contained drug in the Nano medication formed are realized
Mass fraction is up to 80% or more.It is highly preferred that the hydrophobic drug in the first solution and the indocyanine green in the second solution
Mass ratio is 5:2~1:1.
In mixed process, ultrasound and/or stirring are preferably carried out, so that hydrophobic drug is uniformly mixed with indocyanine green.
By controlling the conditions such as the speed, the feed ratio of hydrophobic drug and ICG that are added dropwise, Nano medication can be controlled
Grain size and component ratio.
To get Nano medication after the completion of mixing.The Nano medication of gained can be isolated from mixed solution.Separate mode
It can be centrifugation etc..In one example, centrifuges collection of products and be dispersed in PBS solution:Mixed solution is put into centrifuge
Middle centrifugation obtains Nano medication precipitation.Nano medication precipitation is rinsed with phosphate buffered saline solution (PBS), is then dispersed in
It is preserved in a certain amount of PBS, to carry out a variety of materials characterization and subsequent experimental.
The medicament nano granule molecular dispersivity of gained is good, uniform particle diameter, utilization ratio of drug are high, and Hydrophobic therapeutic drug can account for whole
80% or more of weight.
The preparation method uses the self assembly of indocyanine green (ICG) and dewatering medicament, realizes the Nano medication system of pure drug
It is standby.
Preparation is simple for the disclosure, pollution-free, yield is high, at low cost, efficient, obtained Nano medication grain
Molecular dispersivity is good, size tunable, stability are good, is advantageously implemented the accurate targeting to tumour, generates fabulous therapeutic effect, be
One of the cancer immunotherapies of great application prospect.
Embodiment is enumerated further below so that the present invention will be described in detail.It will similarly be understood that following embodiment is served only for this
Invention is further described, and should not be understood as limiting the scope of the invention, those skilled in the art is according to this hair
Some nonessential modifications and adaptations that bright the above is made all belong to the scope of protection of the present invention.Following examples are specific
Technological parameter etc. is also only an example in OK range, i.e. those skilled in the art can be done properly by the explanation of this paper
In the range of select, and do not really want to be defined in hereafter exemplary concrete numerical value.In following embodiments, if to temperature without especially saying
It is bright, refer both to room temperature.
Embodiment 1
1mg taxols are dissolved in 0.1mL DMSO, the organic solution of 10mg/mL is configured to;Prepare the ICG's of 1mg/mL
NaHCO3(0.05mM) aqueous solution;Under ultrasonic vibration, by the DMSO solution of 0.1mL taxols with 20 μ L per 15s rate by
It is added dropwise in the ICG solution of 0.6mL, solution is made to be uniformly mixed and is self-assembly of Nano medication rapidly;It is collected by centrifugation
(17000rpm, 30min) obtains the precipitation of medicament nano particle;It is washed with PBS, is finally dispersed in 1mLPBS.
Fig. 2 is the TEM figures of the taxol-ICG self-assembled nanometer drugs synthesized in embodiment 1, is intuitively shown regular
Spherical morphology, the dispersibility of uniform grain size and height.
Figure 10 shows the grain size distribution of the taxol-ICG self assembly drugs synthesized in embodiment 1, it can be seen that Japanese yew
Alcohol-ICG self-assembled nanometer drug hydration kinetics diameters are about 100nm or so, have simple spike, illustrate the Nano medication grain size point
Cloth is uniform.
Figure 18 is the photo of the PBS solution of the taxol-ICG synthesized in embodiment 1.It is observed that the distinctive fourth of colloid
Da Er effects.Because the nano particle of synthesis shows ICG colors, it was demonstrated that formed in nano particle and contain ICG.And the Nano medication
It can be stably dispersed in water or PBS solution, be long placed in without generating precipitation, the failed hydrophobic drug for forming nano particle is purple
China fir alcohol can precipitate (such as Figure 19) in water or PBS solution, it can be inferred that gained Nano medication particle is by ICG and hydrophobicity medicine
Object taxol forms.Can be calculated ICG contents in Nano medication by Ultraviolet visible absorption spectrum is 236ppm, and hydrophobic drug
Almost without loss, taxol is 5 with mass ratioes of the ICG in Nano medication:1.
Embodiment 2
1mg camptothecines are dissolved in 0.1mL DMSO, the organic solution of 10mg/mL is configured to;Prepare the ICG's of 1mg/mL
NaHCO3(0.05mM) aqueous solution;Under ultrasonic vibration, by the DMSO solution of 0.1mL camptothecines with 20 μ L per 15s rate by
It is added dropwise in the ICG solution of 0.6mL, solution is made to be uniformly mixed and is self-assembly of Nano medication rapidly;It is collected by centrifugation
(17000rpm, 30min) obtains the precipitation of medicament nano particle;It is washed with PBS, is finally dispersed in 1mLPBS.
Fig. 3 is the TEM figures of the camptothecine-ICG self-assembled nanometer drugs synthesized in embodiment 2, is intuitively shown regular
Spherical morphology, the dispersibility of uniform grain size and height.
Figure 11 shows the grain size distribution of the camptothecine-ICG self assembly drugs synthesized in embodiment 2, it can be seen that camplotheca acuminata
Alkali-ICG self-assembled nanometer drug hydration kinetics diameters are about 400nm or so, have simple spike, illustrate the Nano medication grain size point
Cloth is uniform.
Figure 20 is the photo of the PBS solution of the camptothecine-ICG synthesized in embodiment 2.It is observed that the distinctive fourth of colloid
Da Er effects.Because the nano particle of synthesis shows ICG colors, it was demonstrated that formed in nano particle and contain ICG.And the Nano medication
It can be stably dispersed in water or PBS solution, be long placed in without generating precipitation, the failed hydrophobic drug happiness for forming nano particle
Tree alkali can precipitate (such as Figure 21) in water or PBS solution, it can be inferred that gained Nano medication particle is by ICG and hydrophobicity medicine
Object camptothecine forms.
Embodiment 3
1mg Sorafenibs are dissolved in 0.1mL DMSO, the organic solution of 10mg/mL is configured to;Prepare the ICG's of 1mg/mL
NaHCO3(0.05mM) aqueous solution;Under ultrasonic vibration, the rate by the DMSO solution of 0.1mL Sorafenibs with 20 μ L per 15s
It is added dropwise in the ICG solution of 0.6mL, solution is made to be uniformly mixed and is self-assembly of Nano medication rapidly;Centrifugation is received
Collect (17000rpm, 30min), obtains the precipitation of medicament nano particle;It is washed with PBS, is finally dispersed in 1mLPBS.
Fig. 4 is the TEM figures of the Sorafenib-ICG self-assembled nanometer drugs synthesized in embodiment 3, can equally be found out complete
Spherical morphology, uniform grain size and well dispersibility.
Figure 12 shows the grain size distribution of the Sorafenib-ICG self assembly drugs synthesized in embodiment 3, it can be seen that rope
La Feini-ICG self-assembled nanometer drug hydration kinetics diameters are about 90nm or so, have simple spike, illustrate the Nano medication grain
Diameter is distributed stable homogeneous.
Figure 22 is the photo of the PBS solution of the Sorafenib-ICG synthesized in embodiment 3.It is observed that colloid is distinctive
Tyndall effect.The Nano medication can be stably dispersed in water or PBS solution, be long placed in without generating precipitation, failed to be formed
The hydrophobic drug Sorafenib of nano particle can precipitate (such as Figure 23) in water or PBS solution, it can be inferred that gained nanometer
Drug granule is made of ICG and hydrophobic drug Sorafenib.
Embodiment 4
1mg taxols are dissolved in 0.1mL DMSO, the organic solution of 10mg/mL is configured to;Prepare the ICG's of 1mg/mL
NaHCO3(0.05mM) aqueous solution;Under ultrasonic vibration, by the DMSO solution of 0.1mL taxols with 20 μ L per 15s rate by
It is added dropwise in the ICG solution of 1mL, solution is made to be uniformly mixed and is self-assembly of Nano medication rapidly;It is collected by centrifugation
(17000rpm, 30min) obtains the precipitation of medicament nano particle;It is washed with PBS, is finally dispersed in 1mLPBS.
Fig. 5 is that (feedstock mass is than 1 for the taxol-ICG self-assembled nanometers drug that is synthesized in embodiment 4:1) TEM figures, together
Sample can find out complete spherical morphology, uniform grain size and good dispersibility.
Figure 13 shows the taxol-ICG self assemblies drug synthesized in embodiment 4, and (feedstock mass is than 1:1) particle diameter distribution
Figure, it can be seen that (feedstock mass is than 1 for taxol-ICG self-assembled nanometers drug:1) hydration kinetics diameter is about the left sides 100nm
The right side has simple spike, illustrates the Nano medication particle diameter distribution stable homogeneous.
Embodiment 5
1mg taxols are dissolved in 0.1mL DMSO, the organic solution of 10mg/mL is configured to;Prepare the ICG's of 1mg/mL
NaHCO3(0.05mM) aqueous solution;Under ultrasonic vibration, the DMSO solution of 0.1mL taxols is added dropwise with the rate of 5 μ L/s
Enter into the ICG solution of 0.6mL, solution is made to be uniformly mixed and is self-assembly of Nano medication rapidly;It is collected by centrifugation
(17000rpm, 30min) obtains the precipitation of medicament nano particle;It is washed with PBS, is finally dispersed in 1mLPBS.
Fig. 6 is the TEM figures of the taxol-ICG self-assembled nanometers drug (5 μ L/s of drop rate) synthesized in embodiment 5, directly
Show regular spherical morphology, the dispersibility of uniform grain size and height with seeing.
Figure 14 shows the particle diameter distribution of the taxol-ICG self assemblies drug (5 μ L/s of drop rate) synthesized in embodiment 5
Figure, it can be seen that taxol-ICG self-assembled nanometers drug (5 μ L/s of drop rate) hydration kinetics diameter is about the left sides 120nm
The right side has simple spike, illustrates that the Nano medication particle diameter distribution is uniform.
Embodiment 6
1mg taxols are dissolved in 0.1mL DMSO, the organic solution of 10mg/mL is configured to;Prepare the water-soluble of the ICG of 1mg/mL
Liquid;Under ultrasonic vibration, the rate by the DMSO solution of 0.1mL taxols with 20 μ L per 15s is added dropwise to the ICG of 0.6mL
In solution, so that solution is uniformly mixed and be self-assembly of Nano medication rapidly;(17000rpm, 30min) is collected by centrifugation, obtains
To the precipitation of medicament nano particle;It is washed with PBS, is finally dispersed in 1mLPBS.
Fig. 7 is the TEM figures of taxol-ICG (water sample) the self-assembled nanometer drug synthesized in embodiment 6, is intuitively shown
Go out regular spherical morphology, the dispersibility of uniform grain size and height.
Figure 15 shows the grain size distribution of taxol-ICG (water sample) the self assembly drug synthesized in embodiment 6, can see
It is about 100nm or so to go out taxol-ICG (water sample) self-assembled nanometer drug hydration kinetics diameter, has simple spike, illustrates that this is received
Rice diameter of aspirin particle distribution is uniform.
Embodiment 7
1mg camptothecines are dissolved in 0.1mL DMSO, the organic solution of 10mg/mL is configured to;Prepare the water-soluble of the ICG of 1mg/mL
Liquid;Under ultrasonic vibration, the rate by the DMSO solution of 0.1mL camptothecines with 20 μ L per 15s is added dropwise to the ICG of 0.6mL
In solution, so that solution is uniformly mixed and be self-assembly of Nano medication rapidly;(17000rpm, 30min) is collected by centrifugation, obtains
To the precipitation of medicament nano particle;It is washed with PBS, is finally dispersed in 1mLPBS.
Fig. 8 is the TEM figures of camptothecine-ICG (water sample) the self-assembled nanometer drug synthesized in embodiment 7, is intuitively shown
Go out regular spherical morphology, the dispersibility of uniform grain size and height.
Figure 16 shows the grain size distribution of camptothecine-ICG (water sample) the self assembly drug synthesized in embodiment 7, can see
It is about 400nm or so to go out camptothecine-ICG (water sample) self-assembled nanometer drug hydration kinetics diameter, has simple spike, illustrates that this is received
Rice diameter of aspirin particle distribution is uniform.
Embodiment 8
1mg Sorafenibs are dissolved in 0.1mL DMSO, the organic solution of 10mg/mL is configured to;Prepare the water of the ICG of 1mg/mL
Solution;Under ultrasonic vibration, the rate by the DMSO solution of 0.1mL Sorafenibs with 20 μ L per 15s is added dropwise to 0.6mL's
In ICG solution, so that solution is uniformly mixed and be self-assembly of Nano medication rapidly;Be collected by centrifugation (17000rpm,
30min), the precipitation of medicament nano particle is obtained;It is washed with PBS, is finally dispersed in 1mLPBS.
Fig. 9 is the TEM figures of Sorafenib-ICG (water sample) the self-assembled nanometer drug synthesized in embodiment 8, is intuitively shown
Regular spherical morphology, the dispersibility of uniform grain size and height are shown.
Figure 17 shows the grain size distribution of Sorafenib-ICG (water sample) the self assembly drug synthesized in embodiment 8, can be with
Find out that Sorafenib-ICG (water sample) self-assembled nanometer drug hydration kinetics diameter is about 100nm or so, has simple spike, explanation
The Nano medication particle diameter distribution is uniform.
Claims (10)
1. a kind of Nano medication, which is characterized in that the Nano medication is obtained by hydrophobic drug and indocyanine green self assembly
Nano-particle.
2. Nano medication according to claim 1, which is characterized in that the nano-particle be spherical morphology, grain size be 5~
400nm。
3. Nano medication according to claim 1 or 2, which is characterized in that the hydrophobic drug is hydrophobic anticancer medicine
Object preferably is selected from least one of taxol, camptothecine, Sorafenib.
4. Nano medication according to any one of claim 1 to 3, which is characterized in that described to dredge in the Nano medication
Aqueous pharmaceutical accounts for 80% of total quality or more.
5. Nano medication according to any one of claim 1 to 4, which is characterized in that the Nano medication does not contain it
Its carrier.
6. the preparation method of the Nano medication described in a kind of any one of claim 1 to 5, which is characterized in that including following step
Suddenly:
(1)Hydrophobic drug is dissolved in dimethyl sulfoxide (DMSO), the first solution is obtained;
(2)Indocyanine green is dissolved in water or NaHCO3In aqueous solution, the second solution is obtained;
(3)First solution is mixed with the second solution, by being self-assembly of Nano medication.
7. preparation method according to claim 6, which is characterized in that the hydrophobic drug in the first solution and the second solution
In indocyanine green feedstock mass ratio 5:1 to 1:It is adjustable between 2.
8. the preparation method described according to claim 6 or 7, which is characterized in that step(3)In, the first solution is added dropwise to
To mix the first solution with the second solution in two solution, it is preferable that drop rate is 1~5 μ L/s.
9. the preparation method according to any one of claim 6 to 8, which is characterized in that step(3)In, using stirring and/
Or it is nanostructure that the mode of ultrasound, which makes hydrophobic drug be uniformly mixed self assembly in turn with indocyanine green,.
10. the preparation method according to any one of claim 6 to 9, which is characterized in that further include by Nano medication from mixed
It closes and is separated in solution, it is preferable that detached using the method for centrifugation.
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