CN107343962A - Prussian blue nano and its synthetic method - Google Patents
Prussian blue nano and its synthetic method Download PDFInfo
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- CN107343962A CN107343962A CN201610308888.4A CN201610308888A CN107343962A CN 107343962 A CN107343962 A CN 107343962A CN 201610308888 A CN201610308888 A CN 201610308888A CN 107343962 A CN107343962 A CN 107343962A
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Abstract
Using Prussian blue crystalline powder it is a kind of molecular formula of Material synthesis as Fe the present invention relates to one kind4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof and synthetic method.The freeze-dried powder that nano-particle of this method synthesis and combinations thereof or nano-particle and combinations thereof solution or nano-particle and combinations thereof solution are made can be used for preparing T1 mri contrast agents or T2 mri contrast agents and human body or the thallium of animal and the antidote of other heavy metal poisonings.
Description
Technical field
Using Prussian blue crystalline powder it is a kind of molecular formula of Material synthesis as Fe the present invention relates to one kind4[Fe(CN)6]3·nH2The general Shandongs of O
Scholar's indigo plant nano-particle and combinations thereof and synthetic method.Nano-particle of this method synthesis and combinations thereof or nano-particle and
The freeze-dried powder that its composition solution or nano-particle and combinations thereof solution are made can be used for preparing T1 mri contrast agents or T2
The antidote of the thallium and its heavy metal poisoning of mri contrast agent and human or animal.
Background technology
Using Prussian blue crystalline powder it is a kind of molecular formula of Material synthesis as Fe the present invention relates to one kind4[Fe(CN)6]3·nH2The general Shandongs of O
Scholar's indigo plant nano-particle and combinations thereof and synthetic method.Nano-particle of this method synthesis and combinations thereof or nano-particle and
The freeze-dried powder that its composition solution or nano-particle and combinations thereof solution are made can be used for preparing T1 mri contrast agents or T2
The antidote of the thallium and its heavy metal poisoning of mri contrast agent and human or animal.
Prussian blue crystalline powder is a kind of highly stable compound, is not dissolved in water, only can be used as the huge sum of money of human or animal
Belong to thallium or the oral antidote of other heavy metal poisonings, it is impossible to be injected intravenously.If make nano-particle or its group by Prussian blue
Compound, by it is Prussian blue make nano-particle or its composition it is scattered in aqueous after can make the intravenous injection system of human or animal
Agent.It is Prussian blue to make nano-particle or its composition according to existing chemistry and medical science general knowledge, make nanoparticle by Prussian blue
Son or the intravenous formulations of the scattered human or animal made afterwards in aqueous of its composition can be used for the nuclear magnetic resonance of human or animal
Image contrast strengthens, and also available for the thallium of human or animal or the antidote of other heavy metal poisonings, is determined with playing intravenous formulations
Shi Dingliang radiographies strengthen or the rapid detoxication of intravenous formulations is to reduce or mitigate thallium and its other heavy metals to human or animal
The infringement of each organ, the particularly infringement to brain.
The content of the invention
Using Prussian blue crystalline powder it is a kind of molecular formula of Material synthesis as Fe the present invention relates to one kind4[Fe(CN)6]3·nH2The general Shandongs of O
Scholar's indigo plant nano-particle and combinations thereof and synthetic method.Nano-particle of this method synthesis and combinations thereof or nano-particle and
The freeze-dried powder that the solution or nano-particle of its composition and combinations thereof solution are made can be used for prepare T1 mri contrast agents or
The antidote of T2 mri contrast agents and the thallium of human or animal and other heavy metal poisonings.
Prussian blue crystalline powder is a kind of highly stable compound, is not dissolved in aqueous, only can be used as human or animal's weight
The oral antidote of thallium or other heavy metal poisonings, it is impossible to be injected intravenously.If Prussian blue crystalline powder is made into nanometer
Particle or its composition, by it is Prussian blue make nano-particle particle or its composition it is scattered in the solution after can make intravenous injection
Preparation, according to existing chemistry and medical science general knowledge, available for human or animal's magnetic resonance imaging Contrast enhanced, also available for people or dynamic
The removing toxic substances of the thallium of thing and other heavy metal poisonings.
Distribute that bright to be related to a kind of molecular formula be Fe4[Fe(CN)6]3·nH2O prussian blue nanos particle or its composition, it uses sweet dew
The x-ray diffractogram of powder that alcohol does the powder of excipient is shown in Fig. 2;It makes the powder X-ray of excipient powders of polyvinylpyrrolidone
X ray diffration pattern x is shown in Fig. 1 (influence at mannitol X-ray diffraction peak being avoided, to identify the chemical constitution of nanometer);It is assigned with other
The x-ray diffractogram of powder that powder is done in shape agent must have Prussian blue X-ray diffraction peak.
It is Fe the present invention relates to a kind of molecular formula4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof, its synthesis side
Method is, using Prussian blue crystalline powder as raw material, by its corrosion formula for mannitol, meglumine, polyvinylpyrrolidone,
Nicotinic acid, natrium adetate, cysteine the aqueous solution in;Or corrosion is mannitol, meglumine, polyvinylpyrrolidine in formula
Ketone, nicotinic acid, natrium adetate the aqueous solution in;Or corrosion is mannitol, meglumine, polyvinylpyrrolidone, cigarette in formula
In sour, cysteine the aqueous solution;Or corrosion formula for mannitol, meglumine, polyvinylpyrrolidone, natrium adetate,
In the aqueous solution of cysteine;Or corrosion is mannitol, in the aqueous solution of meglumine, polyvinylpyrrolidone, nicotinic acid in formula;
Or corrosion is mannitol, in the aqueous solution of meglumine, polyvinylpyrrolidone, natrium adetate in formula;Or corrosion is being formulated
For mannitol, meglumine, polyvinylpyrrolidone, cysteine the aqueous solution in;Or corrosion is mannitol, Portugal's first in formula
Amine, polyvinylpyrrolidone the aqueous solution in;Or corrosion is mannitol, meglumine, nicotinic acid, natrium adetate, half in formula
In the aqueous solution of cystine, stir to solution it is transparent after, add after polyvinylpyrrolidone that to continue stirring transparent to solution;Or
Corrosion be formulated for mannitol, meglumine, nicotinic acid, natrium adetate, the aqueous solution in, stir to solution it is transparent after, then add
Enter to continue stirring after polyvinylpyrrolidone transparent to solution;Or corrosion is mannitol, meglumine, nicotinic acid, half Guang ammonia in formula
In the aqueous solution of acid, stir to solution it is transparent after, add after polyvinylpyrrolidone that to continue stirring transparent to solution;Or corrosion
Be formulated for mannitol, meglumine, natrium adetate, cysteine the aqueous solution in, stir to solution it is transparent after, add
It is transparent to solution to continue stirring after polyvinylpyrrolidone;Or corrosion is mannitol, in the aqueous solution of meglumine, nicotinic acid in formula,
Stirring to solution it is transparent after, add after polyvinylpyrrolidone that to continue stirring transparent to solution;Or corrosion formula for mannitol,
Meglumine, natrium adetate the aqueous solution in, stir to solution it is transparent after, add after polyvinylpyrrolidone and continue stirring extremely
Solution is transparent;Or corrosion be formulated for mannitol, meglumine, cysteine the aqueous solution in, stir to solution it is transparent after, then
It is transparent to solution to continue stirring after addition polyvinylpyrrolidone;In said process, polyvinylpyrrolidone can be substituted with chitosan,
Or can be substituted with dextran, or carboxyl dextran can be used to substitute, or can be substituted with glucan, or Sensor Chip CM 5 can be used
Substitute, or can be substituted with polyethylene glycol, or with polyvinylpyrrolidone and its one or more mixtures of substitute, each composition
Dosage is that mannitol is 2-20% (weight), and meglumine is 2%-20% (weight), and nicotinic acid is 0.01-5.0% (weight), according to ground
Acid disodium is 0.01-5.0% (weight), and cysteine is 0.01%-5.0% (weight), and polyvinylpyrrolidone is 2%-20% (weights
Amount), chitosan is 1.0%-15% (weight), and dextran is 1.0%-15% (weight), and carboxyl dextran is 1.0%-15%
(weight), glucan are 1.0%-15% (weight), and Sensor Chip CM 5 is 1.0%-15% (weight), polyethylene glycol 1.0%-20%
(weight), in said process, each composition all continues to stir 0.5-36 hours after dissolving or corrosion, and forming stable molecular formula is
Fe4[Fe(CN)6]3·nH2The solution or its nanometer of O prussian blue nano particles and combinations thereof or its nano-particle and combinations thereof
The freeze-dried powder that the solution of particle and combinations thereof is made.
It is Fe the present invention relates to a kind of molecular formula4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof or its nanoparticle
The solution that son and combinations thereof is made, or the freeze-dried powder that its nano-particle and combinations thereof solution is made, can be used as T1 nuclear magnetic resonance
Contrast agent.
It is Fe the present invention relates to a kind of molecular formula4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof or its nanoparticle
The solution that son and combinations thereof is made, or the freeze-dried powder that its nano-particle and combinations thereof solution is made, can be used as T2 nuclear magnetic resonance
Contrast agent.
It is Fe the present invention relates to a kind of molecular formula4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof or its nanoparticle
The solution that son and combinations thereof is made, or the freeze-dried powder that its nano-particle and combinations thereof solution is made, can be used as human or animal's
The antidote of thallium or other heavy metal poisonings.
It is Fe the present invention relates to a kind of molecular formula4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof or its nanoparticle
The solution that son and combinations thereof is made, or the freeze-dried powder that its nano-particle and combinations thereof solution is made, can make oral formulations.
It is Fe the present invention relates to a kind of molecular formula4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof or its nanoparticle
The solution that son and combinations thereof is made, or the freeze-dried powder that its nano-particle and combinations thereof solution is made, intravenous injection system can be made
Agent.
It is Fe the present invention relates to a kind of molecular formula4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof or its nanoparticle
The solution that son and combinations thereof is made, or the freeze-dried powder that its nano-particle and combinations thereof solution is made, its Nanoparticle Size exist
Between 1mm-100nm, the nanoparticle morphology of its transmission electron microscope is shown in Fig. 3, Fig. 5 etc.;The nano-particle power spectrum of its transmission electron microscope
Display only iron content, is shown in Fig. 4, Fig. 6 etc.;
Nanoparticle compositions solution iron-holder is between 0.1-100mM;
Nanoparticle compositions solution PH is stable between PH3.5-12.6, and PH has preferably biology between PH7.6-10.5
Compatibility;
Free ferric ion concentration is less than 5ppm.
It is Fe by molecular formula4[Fe(CN)6]3·nH2O prussian blue nanos and combinations thereof or its nano-particle and combinations thereof solution,
Or the freeze-dried powder that its nano-particle and combinations thereof solution is made, the concentration of the 2-50mM containing ferric iron is configured to, by 0.22 μm
Miillpore filter is sterile filtered, aseptic subpackaged into cillin bottle, that is, liquid nano mri contrast agent is made, can injection for intravenous
Use;
It is Fe by molecular formula4[Fe(CN)6]3·nH2O prussian blue nanos and combinations thereof or its nano-particle and combinations thereof solution,
Or the freeze-dried powder that its nano-particle and combinations thereof solution is made, the 2-50mM of iron containing trivalent concentration is configured to, by 0.22 μm
Miillpore filter is sterile filtered, and gained filtrate is dried in vacuo by sterile spray chilling or aseptic subpackaged passes through vacuum refrigeration into cillin bottle
Drying means processing, that is, it is Fe that molecular formula, which is made,4[Fe(CN)6]3·nH2O prussian blue nanos and combinations thereof solution or its nanometer
The freeze-dried powder solid state nmr contrast agent that particle and combinations thereof solution is made, its x-ray diffractogram of powder are shown in Fig. 3, Fig. 5,
The molecular structure for proving the nano-particle in the nano-particle or its composition is Fe4[Fe(CN)6]3·nH2O;Injection is used before use
Water or the dilution of injection physiological saline or 5% glucose, the 2-50mM of iron containing trivalent concentration is made into, can injection for intravenous use.
Molecular formula is Fe4[Fe(CN)6]3·nH2O prussian blue nanos and combinations thereof or its nano-particle and combinations thereof solution,
Or the T1 relaxation rates of freeze-dried powder that its nano-particle and combinations thereof solution is made are 0.7599mmolL-1s-1, more than Manganese hexacyanoferrate
The T1 relaxation rates 0.6368mmolL of potassium nanometer-1s-1, see Fig. 7.Display molecular formula is Fe4[Fe(CN)6]3·nH2O is Prussian blue
Nano-NMR radiography T1 enhancing effect should be better than Manganese hexacyanoferrate potassium nanometer.
Molecular formula is Fe4[Fe(CN)6]3·nH2O prussian blue nanos and combinations thereof or its nano-particle and combinations thereof solution,
Or the T2 relaxation rates of freeze-dried powder that its nano-particle and combinations thereof solution is made are 1.2074mmolL-1s-1, more than Manganese hexacyanoferrate
The T2 relaxation rates 1.0141mmolL of potassium nanometer-1s-1, see Fig. 8.Display molecular formula is Fe4[Fe(CN)6]3·nH2O is Prussian blue
Nano-NMR radiography T2 enhancing effect should be better than Manganese hexacyanoferrate potassium nanometer.
It is Fe by the molecular formula of the concentration of the 2-50mM containing ferric iron4[Fe(CN)6]3·nH2O prussian blue nano particle compositions are molten
Liquid 1-3ml is expelled to big white mouse tail vein, and raises 2 weeks, big white mouse outward appearance and behavior no abnormality seen during raising.
Brief description of the drawings
Fig. 1 is that the molecular formula prepared by the embodiment of the present invention 4 (being free of mannitol) is Fe4[Fe(CN)6]3·nH2O is Prussian blue to be received
Nanoparticle composition freeze-dried powder x-ray diffractogram of powder.
Fig. 2 is that the molecular formula prepared by the embodiment of the present invention 2 (containing mannitol) is Fe4[Fe(CN)6]3·nH2O prussian blue nanos
The freeze-dried powder x-ray diffractogram of powder of particle composition.
Fig. 3 is that the molecular formula prepared by the embodiment of the present invention 1 is Fe4[Fe(CN)6]3·nH2O prussian blue nano particle compositions are molten
Liquid transmission electron microscope picture.
Fig. 4 is that the molecular formula prepared by the embodiment of the present invention 1 is Fe4[Fe(CN)6]3·nH2O prussian blue nano particle compositions
Solution transmission electron microscope power spectrum elementary analysis figure.
Fig. 5 is that the molecular formula prepared by the embodiment of the present invention 3 is Fe4[Fe(CN)6]3·nH2O prussian blue nano particle compositions are molten
Liquid transmission electron microscope picture.
Fig. 6 is that the molecular formula prepared by the embodiment of the present invention 3 is Fe4[Fe(CN)6]3·nH2O prussian blue nano particle compositions
Solution transmission electron microscope power spectrum elementary analysis figure.
Fig. 7 is that the molecular formula obtained by the embodiment of the present invention 1 is Fe4[Fe(CN)6]3·nH2O prussian blue nano particle compositions are molten
The T1 relaxation rates of liquid sample compare figure.
Fig. 8 is that the molecular formula obtained by the embodiment of the present invention 1 is Fe4[Fe(CN)6]3·nH2O prussian blue nano particle compositions are molten
The T2 relaxation rates of liquid sample compare figure.
Fig. 9 is that the molecular formula obtained by the present invention is applied in example 6 is Fe4[Fe(CN)6]3·nH2O prussian blue nanos particle composition freezes
The rat liver magnetic resonance imaging experiment that dry powder sample G is done, passes through tail vein injection to big white mouse body by 1ml/300g dosage
It is interior, do magnetic resonance imaging, must inject respectively before and injection after 20 minutes when rat liver magnetic resonance imaging T1 images and
Signal value.
Figure 10 is that the molecular formula obtained by the present invention is applied in example 6 is Fe4[Fe(CN)6]3·nH2O prussian blue nano particle compositions
The rat liver magnetic resonance imaging experiment that freeze-dried powder sample G is done, passes through tail vein injection to big white mouse by 1ml/300g dosage
In vivo, do magnetic resonance imaging, must inject respectively before and injection after 20 minutes when rat liver magnetic resonance imaging T2 images
And signal value.
Embodiment
Embodiment 1:
Molecular formula is Fe4[Fe(CN)6]3·nH2The preparation of O prussian blue nano particles and combinations thereof
Weigh 4.80g mannitol, meglumine 5.60g, nicotinic acid 0.0400g, natrium adetate 0.0040g, cysteine 0.0400g
In 100ml beakers, 70ml is added water to, magnetic agitation, to being completely dissolved, abbreviation sample A.
Polyvinylpyrrolidone 4.8g is weighed again to add in sample A, is stirred continuously, is completely dissolved to polyvinylpyrrolidone, referred to as
Sample B.
It is Fe to weigh molecular formula4[Fe(CN)6]3Prussian blue crystalline powder 0.3437g is added in sample B, is stirred continuously, and extremely should
Complete corrosion is crystallized, continues stirring 36 hours, it is Fe to obtain molecular formula4[Fe(CN)6]3Prussian blue crystalline nanoparticles composition is molten
Liquid, abbreviation sample C.The pH value for measuring sample C is 8.5;Transmission electron microscope observation is balanced in the solution to sample C nano particle
Distribution, particle diameter are shown in Fig. 3 in 20-40nm;Transmission electron microscope elementary analysis power spectrum measures in sample C only iron content, sees Fig. 4;
With free iron in reverse osmosis unit separation sample C, the free ferric ion concentration separated with atomic absorption method measurement,
Calculate that the ferric ion concentration that dissociates in sample C is 1.2ppm.
Embodiment 2:
It is Fe by molecular formula prepared in embodiment 14[Fe(CN)6]3Prussian blue crystalline nanoparticles composition solution sample C matches somebody with somebody
The concentration of the 20mM containing ferric iron is made, is sterile filtered by 0.22 μm of miillpore filter, is freeze-dried, makes freeze-dried powder,
Abbreviation sample D, sampling D do powder x-ray diffraction test, it was demonstrated that contained nano-particle obtains chemical constitution and is in freeze-dried powder
Fe4[Fe(CN)6]3, but the wherein powder x-ray diffraction characteristic absorption peak of mannitol and Prussian blue powder x-ray diffraction is special
It is very close to levy absworption peak, has certain interference to Prussian blue identification, sees Fig. 2.
Embodiment 3:
Molecular formula without mannitol is Fe4[Fe(CN)6]3·nH2The preparation of O prussian blue nano particles and combinations thereof
Meglumine 5.60g, nicotinic acid 0.0400g, natrium adetate 0.0040g, cysteine 0.0400g are weighed in 100ml beakers
In, add water to 70ml, magnetic agitation, to being completely dissolved, abbreviation sample A1.
Polyvinylpyrrolidone 4.8g is weighed again to add in sample A1, is stirred continuously, is completely dissolved to polyvinylpyrrolidone, letter
Claim sample B1.
It is Fe to weigh molecular formula4[Fe(CN)6]3Prussian blue crystallization 0.3437g is added in sample B1, is stirred continuously, to the crystallization
Complete corrosion, continue stirring 36 hours, it is Fe to obtain molecular formula4[Fe(CN)6]3Prussian blue crystalline nanoparticles solution, abbreviation sample
C1.For transmission electron microscope observation to sample C1 nano-particles equiblibrium mass distribution in the solution, particle diameter is shown in Fig. 5 in 20-40nm;Thoroughly
Penetrate electron microscope elementary analysis power spectrum and measure sample C1 only iron content, see Fig. 6;With free iron in reverse osmosis unit separation sample C1 from
Son, the free iron ion concentration separated with atomic absorption method measurement, calculate that iron ion concentration of dissociating in sample C1 is 1.2ppm;
Embodiment 4:
It is Fe by molecular formula prepared in embodiment 34[Fe(CN)6]3Prussian blue crystalline nanoparticles composition solution sample C1
The concentration of the 20mM containing ferric iron is configured to, is sterile filtered by 0.22 μm of miillpore filter, is freeze-dried, made lyophilized
Powder, abbreviation sample D1, sampling D1 do powder x-ray diffraction test, it was demonstrated that nano-particle molecular structure is in freeze-dried powder
Fe4[Fe(CN)6]3, the powder x-ray diffraction peak of mannitol contained by sample D in embodiment 2 is clearly eliminated to molecule in freeze-dried powder
Formula is Fe4[Fe(CN)6]3The interference of the determination of chemical structure of Prussian blue crystalline nanoparticles composition, is shown in Fig. 1.
Embodiment 5:
By Fe prepared in embodiment 14[Fe(CN)6]3Prussian blue crystalline nanoparticles composition solution sample C is configured to contain three
Valency iron 20mM concentration, it is sterile filtered by 0.22 μm of miillpore filter, it is aseptic subpackaged into cillin bottle, that is, liquid is made
Molecular formula Fe4[Fe(CN)6]3Prussian blue crystalline nanoparticles composition solution mri contrast agent, abbreviation sample E, is available for quiet
Arteries and veins injection uses.
Embodiment 6:
It is Fe by molecular formula prepared in embodiment 14[Fe(CN)6]3Prussian blue crystalline nanoparticles composition solution sample C matches somebody with somebody
The concentration of the 20mM containing ferric iron is made, is sterile filtered by 0.22 μm of miillpore filter, sterile cryo vacuum drying, sterile point
It is attached in cillin bottle, that is, it is Fe that molecular formula, which is made,4[Fe(CN)6]3Prussian blue crystalline nanoparticles composition freeze-dried powder nuclear magnetic resonance
Contrast agent, abbreviation sample F, is preserved in solid form, makes nano-particle therein highly stable, is easy to preserve for a long time, is available for quiet
Arteries and veins injection uses, during use with water for injection be diluted to it is former it is lyophilized before volume, shake up to freeze-dried powder and be all dissolved into colloidal suspension
Shape solution, claim sample G.Also sample F can be diluted and be dissolved as sample G ' with physiological saline or 5% glucose replacement water for injection.
Embodiment 7:
It is Fe by the molecular formula obtained by embodiment 14[Fe(CN)6]3Prussian blue crystalline nanoparticles composition solution sample C is done
T1 relaxation rates, T1 relaxation rates are 0.7599mmoL-1s-1, higher than Manganese hexacyanoferrate potassium nanometer with set of dimensions compound T1 relaxation rates
0.6368mmo·L-1s-1, as a result see Fig. 7.Display molecular formula is Fe4[Fe(CN)6]3Prussian blue crystalline nanoparticles composition core
Magnetic resonance T1 radiographies are better than Manganese hexacyanoferrate potassium nanometer with set of dimensions compound.
Embodiment 8:
It is Fe by the molecular formula obtained by embodiment 14[Fe(CN)6]3Prussian blue crystalline nanoparticles composition solution sample C is done
T2 relaxation rates, T2 relaxation rates are 1.2074mmoL-1s-1, higher than Manganese hexacyanoferrate potassium nanometer with set of dimensions compound T2 relaxation rates
1.0141mmo·L-1s-1, as a result see Fig. 8.Display molecular formula is Fe4[Fe(CN)6]3Prussian blue crystalline nanoparticles composition core
Magnetic resonance T2 radiographies are better than Manganese hexacyanoferrate potassium nanometer with set of dimensions compound.
Embodiment 9:
It is Fe by the molecular formula obtained by embodiment 64[Fe(CN)6]3Prussian blue crystalline nanoparticles composition freeze-dried powder sample G
(containing ferric iron 20mM) is by 0.4ml/20g dosage by tail vein injection to Mice Body, continuing raising 2 after injecting sample G
In week, the outward appearance and behavior difference situation of mouse are not during which observed.
The dosage that 0.4ml/20g (containing ferric iron 20mM) mouse dosage is converted into rat is 2800mmol/Kg, sample G
The effective dose for doing rat magnetic resonance imaging is 67mmol/Kg (20mM containing ferric iron, dosage 1ml/300g), sample G's
Safe range is more than 40 times of its effective dose.
Embodiment 10:
It is Fe by the molecular formula obtained by embodiment 64[Fe(CN)6]3Prussian blue crystalline nanoparticles composition freeze-dried powder sample G
(containing ferric iron 20mM) is by 1ml/300g dosage by tail vein injection to rat body, observing rat liver nuclear magnetic resonance
T1 and T2 contrasting effects:
The image and its signal value of rat liver nuclear magnetic resonance T1 contrasting effects are shown in Fig. 9, show the enhancing effect of highly significant.
The image and its signal value of rat liver nuclear magnetic resonance T2 contrasting effects are shown in Figure 10, show the enhancing effect of highly significant.
Claims (11)
1. a kind of molecular formula is Fe4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof and synthetic method.
2. molecular formula is Fe according to claim 14[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof, should
The composition of nano-particle and combinations thereof is divided into three parts:
Part I is that molecular formula is Fe4[Fe(CN)6]3·nH2The integral component of O prussian blue nano particle compositions:Molecular formula
For Fe4[Fe(CN)6]3·nH2O prussian blue nanos particle and meglumine;
Part II is that molecular formula is Fe4[Fe(CN)6]3·nH2The coating agent of O prussian blue nano particle compositions:Polyethylene pyrrole
Pyrrolidone, carboxyl dextran, dextran, the alkaline or acid ring-opening product of dextran, glucan, Sensor Chip CM 5,
One or more in the alkaline or acid ring-opening product of glucan, polyethylene glycol;
Part III is that molecular formula is Fe4[Fe(CN)6]3·nH2The form dressing agent of O prussian blue nano particles:Nicotinic acid, half Guang
Zero kind, one or more in propylhomoserin, edetic acid(EDTA), edetate.
3. molecular formula is Fe according to claim 24[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof, its
The freeze-dried powder x-ray diffractogram of powder (see Fig. 1) of excipient is made of polyvinylpyrrolidone, is molecular formula described in claim 2
For Fe4[Fe(CN)6]3·nH2The powder x-ray diffraction characteristic absorption peak of O prussian blue nano particles and combinations thereof.
4. molecular formula is Fe according to claim 24[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof, its
The freeze-dried powder x-ray diffractogram of powder (see Fig. 2) of excipient is made of mannitol, be claim 2 described in molecular formula be
Fe4[Fe(CN)6]3·nH2The powder x-ray diffraction characteristic absorption peak of O prussian blue nano particles and combinations thereof.
5. molecular formula is Fe according to claim 24[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof, its
The freeze-dried powder x-ray diffractogram of powder made of other excipient must have Prussian blue X-ray diffraction peak.
6. molecular formula is Fe according to claim 24[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof, its
Synthetic method is, using Prussian blue crystalline powder as raw material, its corrosion is being formulated as mannitol, meglumine, polyvinyl pyrrole
Alkanone, nicotinic acid, natrium adetate, cysteine the aqueous solution in;Or corrosion is mannitol, meglumine, polyethylene in formula
Pyrrolidones, nicotinic acid, natrium adetate the aqueous solution in;Or corrosion is mannitol, meglumine, polyvinylpyrrolidine in formula
Ketone, nicotinic acid, cysteine the aqueous solution in;Or corrosion formula for mannitol, meglumine, polyvinylpyrrolidone, according to ground
Acid disodium, cysteine the aqueous solution in;Or corrosion is mannitol, meglumine, polyvinylpyrrolidone, nicotinic acid in formula
In the aqueous solution;Or corrosion is mannitol, in the aqueous solution of meglumine, polyvinylpyrrolidone, natrium adetate in formula;Or
Corrosion is mannitol, in the aqueous solution of meglumine, polyvinylpyrrolidone, cysteine in formula;Or corrosion is sweet in formula
In the aqueous solution for revealing alcohol, meglumine, polyvinylpyrrolidone;Or corrosion formula for mannitol, meglumine, nicotinic acid, according to ground
Acid disodium, cysteine the aqueous solution in, stir to solution it is transparent after, add after polyvinylpyrrolidone and continue stirring to molten
Liquid is transparent;Or corrosion be formulated for mannitol, meglumine, nicotinic acid, natrium adetate, the aqueous solution in, stir saturating to solution
After bright, add after polyvinylpyrrolidone that to continue stirring transparent to solution;Or corrosion is mannitol, meglumine, cigarette in formula
Acid, cysteine the aqueous solution in, stir to solution it is transparent after, add after polyvinylpyrrolidone that to continue stirring saturating to solution
It is bright;Or corrosion is mannitol, in the aqueous solution of meglumine, natrium adetate, cysteine in formula, is stirred transparent to solution
Afterwards, add after polyvinylpyrrolidone that to continue stirring transparent to solution;Or corrosion is mannitol, meglumine, nicotinic acid in formula
The aqueous solution in, stir to solution it is transparent after, add after polyvinylpyrrolidone that to continue stirring transparent to solution;Or corrosion exists
Be formulated for mannitol, meglumine, natrium adetate the aqueous solution in, stir to solution it is transparent after, add polyvinylpyrrolidine
It is transparent to solution to continue stirring after ketone;Or corrosion is mannitol, in the aqueous solution of meglumine, cysteine in formula, stirring is extremely
After solution is transparent, add after polyvinylpyrrolidone that to continue stirring transparent to solution;In said process, polyvinylpyrrolidone
It can be substituted, or can be substituted with dextran with chitosan, or carboxyl dextran can be used to substitute, or can substituted with glucan, or
It can be substituted, or can be substituted with polyethylene glycol with Sensor Chip CM 5, or one kind or more with polyvinylpyrrolidone and its substitute
Kind mixture, each Ingredient Amount is that mannitol is 2-20% (weight), and meglumine is 2%-20% (weight), nicotinic acid 0.01-5.0%
(weight), natrium adetate are 0.01-5.0% (weight), and cysteine is 0.01%-5.0% (weight), polyvinylpyrrolidine
Ketone is 2%-20% (weight), and chitosan is 1.0%-15% (weight), and dextran is 1.0%-15% (weight), and carboxyl is right
It is 1.0%-15% (weight) to revolve sugared acid anhydride, and glucan is 1.0%-15% (weight), and Sensor Chip CM 5 is 1.0%-15% (weight),
Polyethylene glycol is 1.0%-20% (weight), and in said process, each composition all continues to stir 0.5-36 hours after dissolving or corrosion,
It is Fe to form stable molecular formula4[Fe(CN)6]3·nH2O prussian blue nano particles and combinations thereof or its nano-particle and its group
The freeze-dried powder that polymer solution or its nano-particle and combinations thereof solution are made.
7. molecular formula is that molecular formula is Fe according to claim 14[Fe(CN)6]3·nH2O prussian blue nanos particle and its group
The solution of compound or its nano-particle and combinations thereof, or the freeze-dried powder of its nano-particle and combinations thereof, can be used as T1 nuclear-magnetisms and are total to
Shake contrast agent.
8. molecular formula is that molecular formula is Fe according to claim 14[Fe(CN)6]3·nH2O prussian blue nanos particle and its group
The solution of compound or its nano-particle and combinations thereof, or the freeze-dried powder of its nano-particle and combinations thereof, can be used as T2 nuclear-magnetisms and are total to
Shake contrast agent.
9. molecular formula is that molecular formula is Fe according to claim 14[Fe(CN)6]3·nH2O prussian blue nanos particle and its group
The solution of compound or its nano-particle and combinations thereof, or the solution lyophilized powder of its nano-particle and combinations thereof, can be used as human body
Or the heavy metal thallium of animal or the antidote of other heavy metal poisonings.
10. molecular formula is that molecular formula is Fe according to claim 14[Fe(CN)6]3·nH2O prussian blue nanos and combinations thereof
Or the solution of its nano-particle and combinations thereof, or the freeze-dried powder of its nano-particle and combinations thereof, oral formulations can be made.
11. molecular formula is that molecular formula is Fe according to claim 14[Fe(CN)6]3·nH2O prussian blue nanos and combinations thereof
Or the solution of its nano-particle and combinations thereof, or the freeze-dried powder of its nano-particle and combinations thereof, intravenous formulations can be made.
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