CN110478499A - A kind of preparation method of BiOI- protein composite nano plate CT images probe - Google Patents

A kind of preparation method of BiOI- protein composite nano plate CT images probe Download PDF

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Publication number
CN110478499A
CN110478499A CN201810460167.4A CN201810460167A CN110478499A CN 110478499 A CN110478499 A CN 110478499A CN 201810460167 A CN201810460167 A CN 201810460167A CN 110478499 A CN110478499 A CN 110478499A
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bioi
protein
composite nano
nano plate
preparation
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沈清明
管慧文
马文康
范曲立
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Nanjing Post and Telecommunication University
Nanjing University of Posts and Telecommunications
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Nanjing Post and Telecommunication University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/04X-ray contrast preparations

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  • Life Sciences & Earth Sciences (AREA)
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Abstract

The invention discloses a kind of preparation methods of BiOI- protein composite nano plate CT images probe, inhibit Bi by addition mannitol3+Hydrolysis, BiOI- protein composite nano plate has been made in water phase at room temperature.The BiOI- protein composite nano plate CT images probe that the present invention prepares has reaction condition mild, the features such as large specific surface area, pattern are uniform, size is controllable, bio-toxicity is low, can be used as CT images probe, in terms of have potential application prospect.It is a kind of ideal method for preparing BiOI- protein composite nano plate CT images probe since invention the method equipment is simple, mild condition, low energy consumption, short preparation period, Yi Shixian.

Description

A kind of preparation method of BiOI- protein composite nano plate CT images probe
Technical field
The present invention relates to the preparation field of nanometer image probe, especially a kind of BiOI- protein composite nano plate CT shadow As the preparation method of probe.
Background technique
The imaging of full name CT scan is imaged in CT, is exactly the usually said x-ray imaging of people.CT imaging with Based on the three-dimensionalreconstruction of X-ray.Its basic principle is that different tissues have different X-ray absorption abilities, and its X-ray Tissue penetration dosage also can be different.Through dosage and numerical digit geometric manipulations are utilized using measurement different parts tissue X-ray Reconstruct tissue fault plane 3-dimensional image.But CT imaging technique is difficult to differentiate the little soft tissue of density difference, it is difficult to obtain The clear image of the soft tissues such as lump, blood vessel.It is therefore desirable to which suitable medium (that is, CT image-forming contrast medium) carrys out enhanced CT imaging Contrast.Need to meet as CT image-forming contrast medium: have powerful X ray attenuation ability, good biocompatibility with And the conditions such as hypotoxicity.
Currently, almost all of internal CT image-forming contrast medium is all to close object containing iodine organification.Although they have good Water solubility, good biocompatibility and the height endurability to human body, but the performance of these organic Cs T image-forming contrast medium sometimes because Its unspecific organ distribution and it is different, can occur acute nephrotoxicity once in a while in shorter imaging time (i.e. about 1.5 hours).Cause This, not yet meets the clinical demand with the CT image-forming contrast medium of longer blood circulatory half-life.
Use various nano particles as contrast agent, when imaging effect and blood circulation can be can increase by having been considered as one kind Between to increase the solution of imaging time window.For example, it was discovered that the Bi of polymer overmold2S3Nanoparticle formulations have higher X-ray absorption, longer circulation time and excellent imaging effect (Nat.Mater.2006,5,118.).However, in vivo Hydrolyzed under acidic conditions Bi2S3It may cause hydrogen sulfide (H2S release), hydrogen sulfide be it is a kind of than hydrogen cyanide (HCN) to nerve and The bigger gas of circulatory system toxicity.We begin look for the good bismuth compound of hydrolytic stability, and can be prepared into small As graininess CT contrast agent, they have good biocompatibility and can be removed by kidney nano particle.
In conclusion disclosure sets forth the iodine oxidations that a kind of simple one-step method synthesis in water has biocompatibility Bismuth-protein nano piece (BiOI), and study their applications as efficient CT contrast agent in experiment made on the living.
Summary of the invention
The present invention is mainly to provide a kind of simple preparation method of BiOI- protein nano piece, and this method has green side Just, the features such as easily operated.The BiOI- protein nano piece being prepared has good biocompatibility and stability, and And it can be applied to CT image-forming contrast medium.Gained BiOI- protein nano piece size is uniform, and preparation process is simple, number of devices Amount is few, and short preparation period, low energy consumption, environmental-friendly, convenient for promoting.
To achieve the above object, the present invention adopts the following technical scheme that, a kind of BiOI- protein composite nano plate CT images The preparation method of probe, comprising the following steps:
Mannitol is dissolved into protein aqueous solution by S1, and five nitric hydrate bismuths are then added, are stirred at room temperature and molten Solution forms the mixed solution containing bismuth ion and protein;
S2 will be added dropwise in the mixed liquor of S1 containing iodine reagent, form Bi-I- protein mixed solution;
The mixed solution of S2 is stirred at room temperature 30~60min, then carries out centrifuge washing with deionized water by S3, from Heart speed is 10000rpm, and 30 DEG C of vacuum drying 12h obtain BiOI- protein composite nano plate.
Technical solution as a further improvement of that present invention, the mannitol concentration in S1 is 2.5~20mmol/L, prevents bismuth The hydrolysis of ion in aqueous solution.
Technical solution as a further improvement of that present invention, the concentration of the bismuth ion solution in S1 are 1~8mmol/L.
Technical solution as a further improvement of that present invention, the protein in S1 refer to bovine serum albumin(BSA), bovine hemoglobin One of white, human serum albumins or human hemoglobin.
Technical solution as a further improvement of that present invention, the concentration of the protein aqueous solution in S1 are 1~10mg/mL.
Technical solution as a further improvement of that present invention, in S2 it is described containing iodine reagent refer to ammonium iodide, sodium iodide or One of potassium iodide.
Technical solution as a further improvement of that present invention, the concentration containing iodine reagent in S2 are 15~650mmol/ L。
The medicine have the advantages that the present invention has directly synthesized BiOI- protein nano under room temperature environment in water phase Piece, without high-temperature heating, required experimental facilities is simple, mild condition, low energy consumption, short preparation period, it is easy to accomplish, convenient for pushing away Extensively;Meanwhile resulting BiOI- protein composite nano plate size is controllable, large specific surface area and size are uniform, reactivity site Increase, good biocompatibility;In addition, resulting BiOI- protein composite nano plate can be dissolved in aqueous solution, and low toxicity, bio-compatible Property it is good, can be applied to biology intracorporal CT imaging.
Detailed description of the invention
Fig. 1 is the transmission electron microscope image of the BiOI- protein nano piece obtained of the embodiment of the present invention 1.
Fig. 2 is X-ray powder diffraction (XRD) figure of the BiOI- protein nano piece obtained of the embodiment of the present invention 1.
Fig. 3 is the infrared spectrogram for the reactant protein used in the embodiment of the present invention 1.
Fig. 4 is the infrared spectrogram of the BiOI- protein nano piece obtained of the embodiment of the present invention 1.
Fig. 5 is the infrared spectrogram of comparative example 1 of the present invention BiOI nano material obtained.
Fig. 6 is the internal and external CT imaging of the BiOI- protein nano piece obtained of the embodiment of the present invention 1 and its strong Degree-concentration relationship figure.
Specific embodiment
To make the objectives, technical solutions, and advantages of the present invention clearer, right in the following with reference to the drawings and specific embodiments The present invention is described in detail.
Embodiment 1:
S1: the mannitol of 0.5mmol being added into 25mL (5mg/mL) Bovine Serum Albumin in Aqueous Solution, and the ox blood is pure At room temperature after stirring and dissolving, the five nitric hydrate bismuth particles of 0.2mmol, room is added in purity > 98%, the molecular weight 68000 of albumen The lower stirring and dissolving 10min of temperature, forms the mixed solution containing bismuth ion and protein;
S2: 1.25mL (316mmol/L) IodineSodium Solution is added dropwise in the mixed liquor of bismuth ion and protein, institute The bismuth ion of addition and the molar ratio of iodide ion are 1:2, stir 1h at room temperature, form BiOI- protein mixed liquor;
S3: by BiOI- protein mixed liquor with deionized water centrifuge washing 3 times, centrifugal speed 10000rpm, when centrifugation Between be 10min, after centrifuge washing, BiOI- protein nano piece is made in 30 DEG C of vacuum drying treatment 12h.
The experimental results showed that under the conditions of nBi:nI=1:2 obtained BiOI- protein nano piece pattern be it is rectangular, For length in 100nm or so, size is uniform, good dispersion.
Embodiment 2:
S1: the mannitol of 0.5mmol being added into 25mL (5mg/mL) Bovine Serum Albumin in Aqueous Solution, and the ox blood is pure At room temperature after stirring and dissolving, the five nitric hydrate bismuth particles of 0.2mmol, room is added in purity > 98%, the molecular weight 68000 of albumen The lower stirring and dissolving 10min of temperature, forms the mixed solution containing bismuth ion and protein;
S2: 1.25mL (158mmol/L) IodineSodium Solution is added dropwise in the mixed liquor of bismuth ion and protein, institute The bismuth ion of addition and the molar ratio of iodide ion are 1:1, stir 1h at room temperature, form BiOI- protein mixed liquor;
S3: by BiOI- protein mixed liquor with deionized water centrifuge washing 3 times, centrifugal speed 10000rpm, when centrifugation Between be 10min, after centrifuge washing, BiOI- protein nano piece is made in 30 DEG C of vacuum drying treatment 12h.
The experimental results showed that irregular in the resulting BiOI- protein nano piece pattern of nBi:nI=1:1, size is not yet It is uniform, and it is few to be centrifuged product.
Embodiment 3:
S1: the mannitol of 0.5mmol being added into 25mL (5mg/mL) Bovine Serum Albumin in Aqueous Solution, and the ox blood is pure At room temperature after stirring and dissolving, the five nitric hydrate bismuth particles of 0.2mmol, room is added in purity > 98%, the molecular weight 68000 of albumen The lower stirring and dissolving 10min of temperature, forms the mixed solution containing bismuth ion and protein;
S2: 1.25mL (474mmol/L) IodineSodium Solution is added dropwise in the mixed liquor of bismuth ion and protein, institute The bismuth ion of addition and the molar ratio of iodide ion are 1:3, stir 1h at room temperature, form BiOI- protein mixed liquor;
S3: by BiOI- protein mixed liquor with deionized water centrifuge washing 3 times, centrifugal speed 10000rpm, when centrifugation Between be 10min, after centrifuge washing, BiOI- protein nano piece is made in 30 DEG C of vacuum drying treatment 12h.
The experimental results showed that resulting BiOI- protein nano piece pattern is 100nm left under the conditions of nBi:nI=1:3 Right is rectangular, and size is uniform, but bad dispersibility, is easy aggregation.
Embodiment 5:
S1: the mannitol of 0.5mmol, the human seralbumin are added into 25mL (5mg/mL) human serum albumins aqueous solution At room temperature after stirring and dissolving, the five nitric hydrate bismuth particles of 0.2mmol, room is added in purity > 98%, the molecular weight 68000 of albumen The lower stirring and dissolving 10min of temperature, forms the mixed solution containing bismuth ion and protein;
S2: 1.25mL (316mmol/L) IodineSodium Solution is added dropwise in the mixed liquor of bismuth ion and protein, institute The bismuth ion of addition and the molar ratio of iodide ion are 1:2, stir 1h at room temperature, form BiOI- protein mixed liquor;
S3: by BiOI- protein mixed liquor with deionized water centrifuge washing 3 times, centrifugal speed 10000rpm, when centrifugation Between be 10min, after centrifuge washing, BiOI- protein nano piece is made in 30 DEG C of vacuum drying treatment 12h.
The experimental results showed that resulting BiOI nano material size is uniform under the conditions of existing for the human serum albumins, point It is good to dissipate property.
Embodiment 6:
S1: the mannitol of 0.5mmol being added into 25mL (5mg/mL) Bovine Serum Albumin in Aqueous Solution, and the ox blood is pure At room temperature after stirring and dissolving, the five nitric hydrate bismuth particles of 0.2mmol, room is added in purity > 98%, the molecular weight 68000 of albumen The lower stirring and dissolving 10min of temperature, forms the mixed solution containing bismuth ion and protein;
S2: 1.25mL (316mmol/L, nBi:nI=1:2) liquor kalii iodide is added dropwise to bismuth ion and protein Mixed liquor in, the molar ratio of the bismuth ion and iodide ion that are added is 1:3, stirs 1h at room temperature, and it is mixed to form BiOI- protein Close liquid;
S3: by BiOI- protein mixed liquor with deionized water centrifuge washing 3 times, centrifugal speed 10000rpm, when centrifugation Between be 10min, after centrifuge washing, BiOI- protein nano piece is made in 30 DEG C of vacuum drying treatment 12h.
The experimental results showed that use potassium iodide as the resulting BiOI- protein nano piece of under conditions of containing iodine reagent Size is uniform, good dispersion.
Comparative example 1:
S1: the mannitol that 0.5mmol is added into 25mL deionized water is added 0.2mmol's at room temperature after stirring and dissolving Five nitric hydrate bismuth particles, stirring and dissolving 10min, forms bismuth ion solution at room temperature;
S2: 1.25mL (316mmol/L) IodineSodium Solution is added dropwise in bismuth ion solution, the bismuth ion being added Molar ratio with iodide ion is 1:2, stirs 1h at room temperature, forms BiOI dirty solution;
S3: by BiOI dirty solution with deionized water centrifuge washing 3 times, centrifugal speed 10000rpm, centrifugation time is 10min, after centrifuge washing, BiOI nano material is made in 30 DEG C of vacuum drying treatment 12h.
The experimental results showed that resulting BiOI appearance of nano material is irregular under the conditions of no bovine serum albumin, size is not It is uniform, bad dispersibility.
Comparative example 2:
S1: the five nitric hydrate bismuth particles of 0.2mmol, institute are added into 25mL (5mg/mL) Bovine Serum Albumin in Aqueous Solution Purity > 98%, the molecular weight 68000 of bovine serum albumin(BSA) are stated, at room temperature stirring and dissolving 10min, forms bismuth ion containing z and albumen The mixed solution of matter;
S2: 1.25mL (316mmol/L, nBi:nI=1:2) IodineSodium Solution is added dropwise to bismuth ion and protein Mixed liquor in, the molar ratio of the bismuth ion and iodide ion that are added is 1:2, stirs 1h at room temperature, and it is mixed to form BiOI- protein Close liquid;
The experimental results showed that bismuth ion is easily hydrolyzed into the solid insoluble of white in the case where no mannitol, cause Reaction cannot normally continue.
Above embodiments are merely to illustrate the present invention and not limit the technical scheme described by the invention, to this specification Understanding should based on person of ordinary skill in the field, although this specification referring to the above embodiments to the present invention Detailed description is had been carried out, still, those skilled in the art should understand that, person of ordinary skill in the field is still Can so modify or equivalently replace the present invention, and all do not depart from the spirit and scope of the present invention technical solution and It is improved, and should all be covered in scope of the presently claimed invention.

Claims (7)

1. a kind of preparation method of BiOI- protein composite nano plate CT images probe, which comprises the following steps:
Mannitol is dissolved into protein aqueous solution by S1, and five nitric hydrate bismuths are then added, is stirred at room temperature and dissolves, Form the mixed solution containing bismuth ion and protein;
S2 will be added dropwise in the mixed liquor of S1 containing iodine reagent, form Bi-I- protein mixed solution;
30~60min is stirred at room temperature in the mixed solution of S2 by S3, then carries out centrifuge washing, centrifugation speed with deionized water Degree is 10000rpm, and 30 DEG C of vacuum drying 12h obtain BiOI- protein composite nano plate.
2. the preparation method of BiOI- protein composite nano plate CT images probe as described in claim 1, it is characterised in that: Mannitol concentration in S1 is 2.5~20mmol/L, prevents the hydrolysis of bismuth ion in aqueous solution.
3. the preparation method of BiOI- protein composite nano plate CT images probe as described in claim 1, it is characterised in that: The concentration of bismuth ion solution in S1 is 1~8mmol/L.
4. the preparation method of BiOI- protein composite nano plate CT images probe as described in claim 1, it is characterised in that: Protein in S1 refers to one of bovine serum albumin(BSA), bovine hemoglobin, human serum albumins or human hemoglobin.
5. the preparation method of BiOI- protein composite nano plate CT images probe as described in claim 1 or 4, feature exist In: the concentration of the protein aqueous solution in S1 is 1~10mg/mL.
6. the preparation method of BiOI- protein composite nano plate CT images probe as described in claim 1, it is characterised in that: The iodine reagent that contains in S2 refers to one of ammonium iodide, sodium iodide or potassium iodide.
7. the preparation method of BiOI- protein composite nano plate CT images probe as described in claim 1 or 6, feature exist In: the concentration containing iodine reagent in S2 is 15~650mmol/L.
CN201810460167.4A 2018-05-15 2018-05-15 A kind of preparation method of BiOI- protein composite nano plate CT images probe Pending CN110478499A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104876266A (en) * 2015-04-21 2015-09-02 南京邮电大学 Aqueous-phase preparation method of bismuth sulfide/protein composite nanospheres

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104876266A (en) * 2015-04-21 2015-09-02 南京邮电大学 Aqueous-phase preparation method of bismuth sulfide/protein composite nanospheres

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MURTHI S. K等: "Synthesis, Characterization, and X ray Attenuation Properties of Ultrasmall BiOI Nanoparticles: Toward Renal Clearable Particulate CT Contrast Agents", 《INORGANIC CHEMISTRY》 *

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