CN106539798B - A kind of preparation method and medicinal application of magnesium (II) -5 FU 5 fluorouracil nanosizing particle - Google Patents
A kind of preparation method and medicinal application of magnesium (II) -5 FU 5 fluorouracil nanosizing particle Download PDFInfo
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- CN106539798B CN106539798B CN201610955002.5A CN201610955002A CN106539798B CN 106539798 B CN106539798 B CN 106539798B CN 201610955002 A CN201610955002 A CN 201610955002A CN 106539798 B CN106539798 B CN 106539798B
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- fluorouracil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
Abstract
The present invention provides a kind of magnesium (II) -5 FU 5 fluorouracil nanosizing particle preparation methods and medicinal application, belong to nanosizing drug material preparation technical field.The present invention uses magnesium nitrate, and 5 FU 5 fluorouracil generates magnesium (II) -5 FU 5 fluorouracil nano particle as raw material, by one step of atomization ultrasound method, nanocrystalline needed for obtaining after centrifugation drying.This preparation method is simple, one-step shaping, and preparation condition is mild；Convenient for regulation, product has good dispersibility and external anticancer effect for reaction.
Description
Technical field
The present invention relates to technical field of nanometer material preparation, and in particular to a kind of magnesium (II) -5 FU 5 fluorouracil nanometer chemical drug
The preparation method and application of composition granule.
Background technique
For the multidrug resistance problem existing for tumor therapeutic agent, siRNA that is currently used for, it is administered in combination two kinds or two kinds
For the treatment means of the above difference mechanism by the clinical applications of more and more investment oncotherapies, the combinations of different treatment means can be with
The formulation rate that single drug, siRNA etc. are reduced while reaching certain therapeutic effect, to substantially reduce the generation of drug resistance
Speed.It is for example combined anticancer drug, anticancer drug and the sensitizer, siRNA and drug etc. of different mechanisms, therefore for properly total
The demand for transporting carrier is growing.Existing nano-carrier has certain since its enrichment in the cell makes it all
Side effect, such as gold nano grain, carbon nanotube and silica dioxide granule are all nondegradable.And pass through FDA certification can
Degradation polymer carrier poly lactic-co-glycolic acid (PLGA), its degradation can generate the acid of high concentration in the tissue of its enrichment
Property oligomer so as to cause ordinary cells acid poisoning low ph conditions.
Summary of the invention
In view of the above-mentioned deficiencies in the prior art, it is an object of the present invention to provide a kind of magnesium (II) -5 FU 5 fluorouracil nano material
Preparation method, nanoscale magnesium (II) -5 FU 5 fluorouracil particle is prepared by this method for the first time, and this material have it is good
SiRNA load capacity and biocompatibility.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of preparation method of magnesium (II) -5 FU 5 fluorouracil nano material, it the following steps are included:
(1) preparation of magnesium nitrate aqueous solution；
(2) preparation of 5 FU 5 fluorouracil aqueous solution；
(3) 5 FU 5 fluorouracil aqueous solution obtained by step 2 is placed in atomization ultrasound machine and carries out ultrasound；
(4) by one gained magnesium nitrate aqueous solution of liquid mist steps for importing obtained by step 3, while ultrasound is carried out to it；
(5) centrifugation drying and processing is carried out to precipitating obtained by step 4.
Configuration magnesium nitrate solution uses distilled water as solvent, the molar concentration of the magnesium nitrate aqueous solution in step (1)
For 0.1-0.4mol/L.Volume is 30mL.
Fluorouracil concentration is 0.05mol/L, volume 15mL in step (2), is stirred after the DMSO of 30 μ L is added to molten
Solution.
It is 50W that step (3), which is fish dive atomization ultrasound machine 402A1 type power using ultrasonic machine, ultrasonic time 15 minutes.
Supersonic frequency is 40KHz in step (4).
Step (5) centrifugal rotational speed is 1000r/min, and drying temperature is 60 DEG C, 6 hours.
Compared with prior art, magnesium (II) -5 FU 5 fluorouracil nano material obtained of the present invention has the advantage that
(1) preparation method is simple, one-step shaping.(2) preparation condition is mild, atomization ultrasound, normal temperature and pressure.(3) reaction is convenient for regulation.
(4) product has good dispersibility, good siRNA load capacity and external anticancer effect.Due to exogenous carrier granular
It can bring certain side effect, and carrier-free or drug from drug/siRNA of carrier are total to transport system that there is not been reported, in order to
Reduce to the maximum extent it is unnecessary by carrier bring small molecule/ion enter cell to as much as possible reduce carrier bring
Toxic side effect, we will use method direct construction carrier granular of the drug molecule from carrier.Pass through small molecule anticancer drug
Nano particle unstable under acid condition is constituted with metal ion originally existing in some human bodies etc..Due to cancer cell tissue
PH environment significantly lower than generally organizing weakly acidic, anticancer drug can be released, particle itself is due to metal ion
Bring surface positive potential can load siRNA to realize the total load of medicine/gene.
Detailed description of the invention
Fig. 1 is magnesium obtained by embodiment 1 (II) -5 FU 5 fluorouracil nano particle scanning electron microscope (SEM) photograph.
Fig. 2 is magnesium obtained by embodiment 2 (II) -5 FU 5 fluorouracil nano particle scanning electron microscope (SEM) photograph.
Fig. 3 is magnesium obtained by Application Example 1 (II) -5 FU 5 fluorouracil nano particle load siEIF5A2 gel electricity
Swimming test.
Fig. 4 is that magnesium obtained by Application Example 1 (II) -5 FU 5 fluorouracil load siEIF5A2 nano particle is right in vitro
The MTT toxotest of breast cancer cell.
Specific embodiment
The present invention will be described in detail in the following with reference to the drawings and specific embodiments, but not thereby limiting the invention
Content.
Embodiment 1:
A kind of preparation method of magnesium (II) -5 FU 5 fluorouracil nano material, it the following steps are included:
(1) preparation of magnesium nitrate aqueous solution；
(2) preparation of 5 FU 5 fluorouracil aqueous solution；
(3) 5 FU 5 fluorouracil aqueous solution obtained by step 2 is placed in atomization ultrasound machine and carries out ultrasound；
(4) by one gained magnesium nitrate aqueous solution of liquid mist steps for importing obtained by step 3, while ultrasound is carried out to it；
(5) centrifugation drying and processing is carried out to precipitating obtained by step 4.
Configuration magnesium nitrate solution uses distilled water as solvent, the molar concentration of the magnesium nitrate aqueous solution in step (1)
For 0.1-0.4mol/L.Volume is 30mL.
In step (2) 5 FU 5 fluorouracil concentration be 0.05mol/L, volume 15mL, be added 30 μ L DMSO after stir to
Dissolution.
It is 50W that step (3), which is fish dive atomization ultrasound machine 402A1 type power using ultrasonic machine, ultrasonic time 15 minutes.
Supersonic frequency is 40KHz in step (4).
Step (5) centrifugal rotational speed is 1000r/min, and drying temperature is 60 DEG C, 6 hours.
Magnesium obtained by the present embodiment preparation method (II) -5 FU 5 fluorouracil nano particle is that a kind of average diameter is
The nano particle of 200nm~500nm or so.Surface electropositive is shown, surface potential is+15.6eV, is had to electronegative
The load capacity of siRNA.It is clear that having when magnesium (II) -5 FU 5 fluorouracil nanometer in the gel electrophoresis data of Fig. 3
When the mass ratio of particle and siEIF5A2 reach 100, electrophoresis no longer runs out of individual siEIF5A2 and corresponds to band, illustrates pair
SiEIF5A2 realizes whole loads.SiRNA is loaded as shown in Figure 4, and siEIF5A2 is in vitro to the growth of breast cancer cell
Has certain rejection ability.SiNC is to the adiaphorous nucleic acid sequence of known cell in figure, and lipo is commercialization liposome.
Embodiment 2
Embodiment 2, with embodiment 1, wherein the concentration of magnesium nitrate is changed to 0.25mol/L, as seen in Figure 2, higher
Obtained magnesium (II) -5 FU 5 fluorouracil nano particle further grows up into micron-sized square under concentration.It is well known that with
Nano-carrier reach micron order scale, the load capacity of unit mass and the ability for entering cell can also decline.Illustrate anti-
Answering the concentrations on product form of object magnesium nitrate has significant impact.According to a series of related experiments, optimal concentration 0.1~
0.25mol/L。
Claims (1)
1. a kind of preparation method of magnesium (II) -5 FU 5 fluorouracil nano particle, it the following steps are included:
(1) preparation of magnesium nitrate aqueous solution；
(2) preparation of 5 FU 5 fluorouracil aqueous solution；
(3) 5 FU 5 fluorouracil aqueous solution obtained by step (2) is placed in atomization ultrasound machine and carries out ultrasound；
(4) by magnesium nitrate aqueous solution obtained by liquid mist steps for importing (1) obtained by step (3), while ultrasound is carried out to it；
(5) centrifugation drying and processing is carried out to precipitating obtained by step (4)；
Configuration magnesium nitrate aqueous solution uses distilled water as solvent in step (1), and the molar concentration of the magnesium nitrate aqueous solution is
0.1-0.4mol/L, volume 30mL；
5 FU 5 fluorouracil concentration is 0.05mol/L, volume 15mL in step (2), is stirred after the dimethyl sulfoxide of 30 μ L is added
To dissolution；
It is 50W that step (3), which is fish dive atomization ultrasound machine 402A1 type power using ultrasonic machine, ultrasonic time 15 minutes；
Supersonic frequency is 40KHz in step (4)；
Step (5) centrifugal rotational speed is 1000r/min, and drying temperature is 60 DEG C, 6 hours.
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| CN105505962A (en) * | 2015-12-21 | 2016-04-20 | 中山大学附属第一医院 | Functionalized nano coordination compound gene introduction material and preparation method and application thereof |
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| CN105505962A (en) * | 2015-12-21 | 2016-04-20 | 中山大学附属第一医院 | Functionalized nano coordination compound gene introduction material and preparation method and application thereof |
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| Title |
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| 铜、铁、锌-氟尿嘧啶配合物合成及其对肿瘤细胞增殖的抑制;周轶平 等;《中国组织工程研究》;20140917;第18卷(第39期);第6309-6315页 * |
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