CN115607694B - Radioactive carbon microsphere and its preparation method and application - Google Patents
Radioactive carbon microsphere and its preparation method and application Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
- A61K51/1241—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins
- A61K51/1244—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins microparticles or nanoparticles, e.g. polymeric nanoparticles
- A61K51/1251—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins microparticles or nanoparticles, e.g. polymeric nanoparticles micro- or nanospheres, micro- or nanobeads, micro- or nanocapsules
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- C01B32/05—Preparation or purification of carbon not covered by groups C01B32/15, C01B32/20, C01B32/25, C01B32/30
Abstract
The invention discloses radioactive carbon microspheres and a preparation method and application thereof. The radioactive carbon microsphere includes a porous carbon microsphere and a complex comprising a radionuclide; the porous carbon microsphere has a mesoporous structure, and the average pore diameter of the mesopores is 2-15 nm; the complex containing the radionuclide is distributed in the holes of the mesopores; the specific surface area of the porous carbon microsphere is 6-30 m 2 And/g, wherein the average mesoporous pore diameter of the porous carbon microsphere is 2-15 nm. The radioactive carbon microsphere has high radionuclide loading rate and low standing loss rate and vibration loss rate, so that the safety of the radioactive carbon microsphere during transportation and storage is effectively improved, and the medical application possibility of the radioactive carbon microsphere is improved; moreover, the preparation method of the radioactive carbon microsphere is simple.
Description
Technical Field
The invention relates to the field of medical treatment, in particular to a radioactive carbon microsphere, a preparation method and application thereof.
Background
Malignant tumors are a disease which seriously threatens human health, and various treatment methods are available at present, including chemotherapy, radiation therapy, interventional therapy, biological immunotherapy and the like. As one of the therapies, great progress has been made in providing radioactive materials for positioning cancer patients, the radioactive materials are incorporated into small particles which can be directly implanted into solid tumors of cancer, local cell killing is achieved by using alpha or beta rays released by radioactive elements, the influence on normal cells around tumor cells is reduced, and the safety is improved as much as possible under the condition of ensuring the therapeutic effect.
In the Selective Internal Radiation Therapy (SIRT) technology developed in recent years, radioactive materials are prepared into microspheres with regular sizes, the microspheres are used for being injected into arterial blood supply of a target organ, embolism is formed by utilizing capillary vessels at specific positions and the sizes of the microspheres, the radioactive microspheres are fixed on focus positions, and surrounding tumor cells are killed by utilizing rays with extremely short range emitted by radioactive elements, so that side effects caused by the fact that the microspheres flow to undesired places in blood are avoided.
There are a number of specific applications for SIRT technology. One of them is glass microsphere, which is prepared by mixing 89 Y 2 O 3 Glass microspheres are prepared as components and are required to be subjected to neutron bombardment in a nuclear reactor to be converted into radioactivity 90 Y. The microsphere has a plurality of problems, the density of the glass microsphere is larger (3.6 g/mL), and is obviously higher than the average density of blood (about 1.1 g/mL), so that the microsphere is easy to settle in the blood in advance, and the microsphere needs to be injected once and rapidly during injection, and the settlement is reduced by using the turbulence of the blood, but the effect is not ideal; at the same time nuclear reactor resources are difficult to obtainThe raw material supply is unstable, and isotopes releasing gamma rays are generated after irradiation, thereby generating side effects. The other is 90 The Y-loaded resin microsphere adopts polystyrene-divinylbenzene polymer as a carrier, has the density close to that of blood, is free from sedimentation, has higher technical difficulty in preparation and loading of the resin microsphere, and has the possibility of falling and losing of Y element and certain side effect.
In recent years, carbon material microspheres have potential application prospects in adsorption, catalysis, drug delivery, energy storage and the like. The carbon material is generally divided into three types, namely solid carbon material microspheres, hollow carbon material microspheres and porous carbon material microspheres. The porous carbon material microsphere has excellent properties of high specific surface area, high chemical stability, high adsorptivity and the like, and has wide application in the fields of batteries, adsorption and the like. The carbon material microsphere is used as an adsorption carrier for loading medicines and even radioactive elements, but the carbon material microsphere has few disclosures and needs to be further researched.
Disclosure of Invention
The invention aims to overcome the defects that the carbon microsphere in the prior art cannot realize high loading rate and low loss rate of radioactive elements at the same time, and provides a radioactive carbon microsphere and a preparation method and application thereof. The radioactive carbon microsphere has high radionuclide loading rate and low standing loss rate and vibration loss rate, so that the safety of the radioactive carbon microsphere during transportation and storage is effectively improved, and the medical application possibility of the radioactive carbon microsphere is improved; moreover, the preparation method of the radioactive carbon microsphere is simple.
In order to achieve the above object, the present invention provides the following technical solutions:
one of the technical schemes provided by the invention is as follows: a radioactive carbon microsphere. The radioactive carbon microsphere includes a porous carbon microsphere and a complex comprising a radionuclide;
the porous carbon microsphere has a mesoporous structure, and the average pore diameter of the mesoporous is 2-15 nm; the complex comprising the radionuclide is distributed in the holes of the mesopores;
the specific surface area of the porous carbon microsphere is 6-30 m 2 /g。
In the present invention, the porous carbon microspheres may have a particle size of 1 to 150. Mu.m, preferably 1 to 100. Mu.m, more preferably 10 to 60. Mu.m.
In the invention, the specific surface area of the porous carbon microsphere can be 10-30 m 2 Preferably 12 to 26m 2 /g, e.g. 14.5m 2 /g or 25.5m 2 /g。
In the present invention, the average pore diameter of the mesopores may be 5 to 10nm, preferably 6 to 9nm, for example 6.44nm or 8.48nm.
In the present invention, the radionuclide in the complex containing a radionuclide may be selected from 90 Y、 32 P、 192 Ir、 103 Pd、 89 Sr、 226 Ra、 131 I、 125 I、 188 Re、 186 Re、 153 Sm、 166 Ho、 111 In、 99m Tc、 192 Ir、 226 Ra、 177 Lu、 225 Ac、 212 Bi、 213 Bi and Bi 223 One or more of Ra, preferably 90 Y。
In the present invention, the dosage ratio of the porous carbon microsphere to the radionuclide is preferably 1: (0.033 to 0.233), more preferably 1: (0.067 to 0.233), more preferably 1: (0.1 to 0.233), more preferably 1: (0.113 to 0.167). For example, when the mass of the porous carbon microsphere is 0.15g, the mass of the radionuclide contained in the complex is 5-35 mg; or when the mass of the porous carbon microsphere is 0.15g, the mass of the radionuclide contained in the complex is 10-35 mg; or when the mass of the porous carbon microsphere is 0.15g, the mass of the radionuclide contained in the complex is 15-35 mg; or when the mass of the porous carbon microsphere is 0.15g, the mass of the radionuclide contained in the complex is 17-25 mg.
In the present invention, the radionuclide-containing complex is preferably obtained by reacting a radionuclide-containing solution with a precipitant-containing solution.
Wherein, when the radionuclide is 90 In Y, the solution containing the radionuclide is preferably 90 YCl 3 A solution.
In the solution containing the precipitant, the precipitant is preferably one or more of tartaric acid, EDTA and sodium phosphate; more preferably tartaric acid, or EDTA, or tartaric acid and sodium phosphate. The EDTA is preferably EDTA-2Na.
The second technical scheme provided by the invention is as follows: a preparation method of radioactive carbon microspheres. The preparation method of the radioactive carbon microsphere comprises the following steps in the first mode or the second mode:
mode one: mixing porous carbon microspheres with a solution containing radionuclides, adding a solution containing a precipitant to obtain a reaction solution, and reacting;
mode two: mixing porous carbon microsphere with solution containing precipitant, adding solution containing radionuclide to obtain reaction solution, and reacting.
In the present invention, preferably, in the first and second modes, the porous carbon microsphere has a mesoporous structure, and an average pore diameter of the mesopores is 2 to 15nm; the specific surface areas of the porous carbon microspheres are 6-30 m 2 /g。
In the present invention, the concentration of the radionuclide in the reaction solution may be 0.02 to 0.15mol/L, preferably 0.05 to 0.12mol/L.
In the present invention, the molar concentration of the precipitant in the reaction solution is preferably in excess of the molar concentration of the radionuclide in the reaction solution, more preferably 1.5 to 4 times, for example, the molar concentration of the precipitant is 2 times, 2.3 times, 2.5 times, 2.8 times, 3 times, 3.2 times, 3.5 times or 3.8 times the molar concentration of the radionuclide.
In the present invention, the solution containing the precipitant may be one or more of tartaric acid solution, EDTA solution and sodium phosphate solution; preferably tartaric acid solution, or EDTA solution, or a mixed solution of tartaric acid solution and sodium phosphate solution. The EDTA solution is preferably EDTA-2Na solution.
In the invention, after the reaction is completed, the complex containing the radionuclide can be distributed in the holes of the mesopores; preferably, the radionuclide-containing complex is immobilized within the pores of the mesopores.
In the present invention, the reaction time may be 0.5 to 1.5 hours, for example, 0.6 hours, 0.7 hours, 0.8 hours, 0.9 hours, 1 hour, 1.1 hours, 1.2 hours, 1.3 hours or 1.4 hours.
In the present invention, after the completion of the reaction, a step of washing may be further included. The operation and conditions of the washing may be conventional in the art, such as repeated rinsing with deionized water.
In the invention, the preparation method of the porous carbon microsphere preferably comprises the following steps: the resin microspheres (e.g., phenolic resin microspheres or polystyrene microspheres) are calcined.
Wherein the calcination temperature is preferably 400-800 ℃. In the process of heating from room temperature to the calcination temperature (400-800 ℃), the heating rate can be conventional in the art, for example, 3-10 ℃/min.
Wherein the calcination time is preferably 3 to 6 hours, more preferably 4 hours.
Wherein the calcined atmosphere is preferably an Ar gas atmosphere.
In the present invention, when the preparation method of the radioactive carbon microsphere includes a step of calcining the phenolic resin microsphere, the phenolic resin microsphere may be conventional in the art.
Preferably, the average particle diameter of the phenolic resin microspheres is 1-100 μm, preferably 10-60 μm, more preferably 30-50 μm.
More preferably, the phenolic resin microspheres are prepared by the following method: and (3) reacting the mixed solution of resorcinol, water, an alkaline catalyst, formaldehyde and a dispersing agent at 60-85 ℃ for 40-60 h, for example, at 65 ℃, 68 ℃, 70 ℃, 75 ℃ or 80 ℃ for 45h, 48h, 50h, 55h or 58h.
Wherein the mixture is preferably reacted at 85℃for 48 hours.
Wherein the basic catalyst is preferably selected from NaOH, KOH, ca (OH) 2 、Na 2 CO 3 And K 2 CO 3 One or more of the following; more preferably Na 2 CO 3。
Wherein the dispersing agent is preferably one or more of n-heptane, silicone oil, corn oil and olive oil; more preferably silicone oil.
Wherein, after the mixed solution reaction is completed, the method preferably further comprises the steps of solid-liquid separation, cleaning and drying.
In the present invention, when the method of preparing the radioactive carbon microsphere includes a step of calcining a polystyrene microsphere, the polystyrene microsphere may be conventional in the art, for example, a polystyrene-divinylbenzene microsphere, such as a polystyrene microsphere of dupont AmberChromTM XT30 in the united states.
The third technical scheme provided by the invention is as follows: a radioactive carbon microsphere. The radioactive carbon microsphere is prepared by the preparation method.
The technical scheme provided by the invention is as follows: use of radioactive carbon microspheres as hereinbefore described for the manufacture of a medicament for the treatment of a tumour.
On the basis of conforming to the common knowledge in the field, the above preferred conditions can be arbitrarily combined to obtain the preferred examples of the invention.
The reagents and materials used in the present invention are commercially available.
The invention has the positive progress effects that: according to the invention, the BET multipoint specific surface area and the mesoporous average pore diameter of the prepared porous carbon microsphere are controlled, so that the loading rate of the porous carbon microsphere to radioactive precipitation is effectively improved, the standing loss rate and the vibration loss rate of the porous carbon microsphere are reduced, the safety of the porous carbon microsphere during transportation and storage is improved, and the medical application possibility of the porous carbon microsphere is improved.
Drawings
FIG. 1 is a Scanning Electron Microscope (SEM) image of porous carbon microspheres of example 1.
FIG. 2 is a graph showing the particle size distribution of porous carbon microspheres in example 1.
Fig. 3 is a graph showing the comprehensive distribution of desorption pore volume and pore diameter of the porous carbon microsphere BJH in example 1.
FIG. 4 is a Scanning Electron Microscope (SEM) image of porous carbon microspheres of example 2.
FIG. 5 is a graph showing the particle size distribution of porous carbon microspheres in example 2.
Fig. 6 is a graph showing the comprehensive distribution of desorption pore volume and pore diameter of the porous carbon microsphere BJH of example 2.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
Term interpretation:
in the present invention, the terms "precipitate", "complex precipitate" have the same meaning, and refer to a precipitate formed by reaction with a precipitant to which a metal element (e.g., a radioactive element) is immobilized.
In the present invention, the term "precipitant" refers to a substance capable of reacting with a radionuclide to form particles with significantly reduced solubility, and solid precipitates can be formed, for example, by various reaction types such as complexation, chelation, association, salification, etc. The precipitants are selected from tartaric acid, EDTA and sodium phosphate, 8-hydroxyquinoline, aromatic carboxylic acid, quinolones, flavonols, N '-bis (2-hydroxyphenyl) oxalic acid diamide, dibutyl methylphosphonate (DPMA), trifluoromethanesulfonic acid, 2, 6-di-tert-butyl-4-methylphenol, asparagine/glutamine, oxalate, thiocyanate, pyrophosphate, 5-fluorouracil, methacrylic acid/sorbic acid/salicylic acid and 8-hydroxyquinoline, aromatic carboxylic acid and 1, 10-phenanthroline/4, 4' -bipyridine, oxalic acid and phenanthroline, phenylalanine and phenanthroline, phosphate and serum proteins, nicotinic acid and 8-hydroxyquinoline, isophthalic acid and acetylacetone, indole 3-propionic acid and phenanthroline, aspartic acid and phenanthroline, schiff base and phenanthroline, and the like.
Example 1
Preparing phenolic resin microspheres: 6.4g of resorcinol, 25mL of water and 40mL of silicone oil are magnetically stirred for 5min, 5mL of sodium carbonate aqueous solution (0.0616 g/1000mL, the mol ratio of resorcinol to sodium carbonate is 100:0.005) and 9mL of formaldehyde are added, the mixture is reacted for 30min under the condition of magnetically stirring at 200rpm/min, the mixture is put into a reaction kettle to react for 48h at 85 ℃, the mixture is centrifugally washed for three times by deionized water and absolute ethyl alcohol, vacuum drying is carried out at 60 ℃ for 12h, and the phenolic resin microspheres are obtained after sieving; the average particle size of the phenolic resin microspheres is concentrated at 30-50 mu m.
Preparation of porous carbon microspheres: calcining the phenolic resin microsphere prepared in the above way for 4 hours in Ar atmosphere at 800 ℃ to obtain a porous carbon microsphere; wherein, in the process of heating from room temperature to 800 ℃, the heating rate is 3 ℃/min.
An SEM image of the porous carbon microsphere is shown in fig. 1; the average particle size distribution is concentrated in the range of 25 to 38. Mu.m, as shown in FIG. 2.
The BET multipoint specific surface area of the porous carbon microsphere prepared in example 1 is 14.5m, which is identified by a precise micro-high Bow JW-BK112 mesoporous analyzer 2 And/g, the mesoporous structure is obvious, the mesoporous pore diameter distribution is uniform, and the average mesoporous pore diameter is 6.44nm. The graph of the desorption pore volume-pore diameter integrated distribution of the porous carbon microsphere BJH in example 1 is shown in FIG. 3.
Example 2
Preparation of porous carbon microspheres: the porous carbon microsphere is prepared by calcining polystyrene microsphere (purchased from DuPont AmberChromT XT 30) in Ar atmosphere at 400 deg.C for 4h (the temperature is raised from room temperature to 200 deg.C at 10 deg.C/min, then raised to 400 deg.C at 3 deg.C/min, and then cooled at a rate of 10 deg.C/min after holding for 240 min).
An SEM image of the porous carbon microsphere is shown in fig. 4; the average particle diameter is concentrated to 17 to 21. Mu.m, as shown in FIG. 5.
The BET multipoint specific surface area of the porous carbon microsphere prepared in example 2 is 25.5m, which is identified by a precise micro-high Bow JW-BK112 mesoporous analyzer 2 And/g, the mesoporous structure is obvious, the mesoporous pore diameter distribution is uniform, and the average mesoporous pore diameter is 8.48nm. The graph of the desorption pore volume-pore diameter integrated distribution of the porous carbon microsphere BJH in example 2 is shown in FIG. 6.
Comparative example 1
Referring to Feng, zhao Jianggong, hanxin, etc. the inverse emulsion method is free of emulsifying agent to prepare carbon microsphere and its electrochemical performance [ J ]. Novel carbon material, 2016, 31 (6): 600-608, the preparation method disclosed in the specification is used for preparing carbon microspheres, and the specific steps are as follows:
the heat conduction oil and the silicone oil are mixed according to the mass ratio of 4:1, mixing, preheating and stirring for 1h at 115 ℃. Weighing a certain amount of thermosetting phenolic resin and ethanol (mass ratio of 1:4), mixing and stirring uniformly, slowly pouring the mixed solution into the preheated mixed oil, stirring for 2 hours at 115 ℃ (stirring speed is 500 r/min), filtering, separating, washing and drying to obtain phenolic resin microspheres.
Carbonizing the obtained phenolic resin microsphere for 1h at 800 ℃ in Ar atmosphere to obtain the porous carbon microsphere. The average particle diameter of the prepared porous carbon spheres is concentrated to 10-20 mu m, and the BET multipoint specific surface area is 540m 2 And/g, wherein the average pore diameter of the mesopores is 0.89nm.
Comparative example 2
Adding phloroglucinol (1 eq), resorcinol (1 eq) and formaldehyde (1 eq) into deionized water, stirring and dissolving, stirring for 5min at a high speed of 800r/min, stirring for 5min at a low speed of 100r/min to prepare a precursor solution, adding the precursor solution into industrial white oil containing span-80 with a volume fraction of 1% (the volume ratio of the precursor solution to the industrial white oil is 1:8), stirring and mixing uniformly, and carrying out oil bath reaction at 25 ℃ for 12h to obtain a turbid solution; the turbid solution is filtered and separated by suction, and is washed with dichloromethane for a plurality of times to obtain powdery solid. Carbonizing the powdery solid for 5 hours at 850 ℃ to obtain the porous carbon microsphere. The prepared carbon spheres have the particle size concentrated at 1-10 mu m and BET multipoint specific surface area of 930m 2 And/g, mesoporous average pore diameter of 18.56nm.
Example 3
The porous carbon microspheres prepared in the above examples or comparative examples were soaked in 0.3mol/L dilute nitric acid for 2 hours, then washed with deionized water sequentially for 3 times, and dried for loading the complex containing the radionuclide.
0.15g of porous carbon microsphere and precipitant solution, YCl 3 The solutions were mixed to obtain a reaction solution having a volume of 3mL, and the reaction was carried out and carried out in the following two ways (types of precipitants are shown in tables 1 to 3):
load mode 1: firstly generating a complex containing radionuclide as a substance adsorbed by the porous carbon microsphere, and then carrying out porous carbon microsphere loading; the method comprises the following steps:
YCl is combined with 3 The solution was reacted with the precipitant solution under stirring for 1h (YCl 3 The concentrations of the solution and the precipitant solution are shown in tables 1 to 3, and a Y-precipitant complex suspension is obtained. And adding porous carbon microspheres, and vibrating in a shaking table for 1h to fully load the Y-precipitator complex on the porous carbon microspheres.
Load mode 2: adding the precipitant solution and the porous carbon microsphere to make the precipitant fully enter the mesopores of the porous carbon microsphere, and then adding YCl 3 The solution reacts in the mesoporous of the porous carbon microsphere to generate a complex; alternatively, YCl is added first 3 Solution and porous carbon microsphere to make YCl 3 Fully entering into mesopores of the porous carbon microspheres, adding a precipitant solution, and reacting in the mesopores of the porous carbon microspheres to generate a complex; the method comprises the following steps:
adding porous carbon microsphere into solution containing precipitant to obtain mixed solution, mixing, standing for 12 hr, and adding YCl into the mixed solution 3 The solution was shaken in a shaker for 1h to allow sufficient loading of the radionuclide-containing complex onto the porous carbon microspheres.
When the precipitant is tartaric acid and sodium phosphate, firstly adding the porous carbon microsphere loaded by the Y-tartaric acid complex into sodium phosphate solution, oscillating for 1h in a shaking table, washing and drying to obtain the Y-PO 4 Complex-supported porous carbon microspheres (EDTA is EDTA-2 Na).
And (3) carrying out suction filtration on the reacted porous carbon microsphere solution for 3 times through deionized water, and measuring the final load rate.
And (3) soaking the half of the collected porous carbon microspheres in physiological saline for 6 days, measuring the content of Y ions in the solution, and calculating the standing loss rate.
And (3) soaking the other half of the collected porous carbon microspheres in physiological saline for 6 days, oscillating for 30min in a shaking table every 12h, measuring the content of Y ions in the solution, and calculating the vibration loss rate.
TABLE 1
TABLE 2
TABLE 3 Table 3
From tables 1 to 3, it can be seen that:
(1) The porous carbon microspheres are loaded in a loading mode 1 (namely, a mode of physical adsorption after the formation of the complex), and the static loss rate and the vibration loss rate of the porous carbon microspheres are obviously higher than those of a loading mode 2 (namely, the complex is formed and grown in the mesoporous pores of the porous carbon microspheres), although the loading rate can reach a relatively high level, and the specific examples 3-01 and examples 3-11 can be seen.
(2) In the embodiment of the loading mode 1, although the concentration of the reactant is higher, the complexing reaction is completed before the porous carbon microsphere is added, so that the loading mode is only physical adsorption, the loading firmness is relatively loose, and the porous carbon microsphere is easy to fall off during the subsequent storage and transportation, thereby possibly causing the quality or safety problem of the product.
For the loading mode 2, since the complex is mainly generated in situ in the mesopores, it gradually grows up and is blocked in the mesopores, so the overall loading firmness is relatively high. When the load is gradually reduced, the load rate tends to be gradually increased, but the overall load should not be too low because the main index of the subsequent actual product is the radioactivity of the load.
(3) Taking into account that 90 Y has a half-life of 64.2h and is generally used in medicine 90 In practical application, the interval from the production of the Y product to clinical application is generally only allowed to be no more than 5-6 days, so that the static loss rate and vibration loss rate investigation indexes with the period of 6 days are set to investigate the Y productQuality and safety control during normal storage and during extreme storage. In addition, the load rate also affects the production cost and the complexity of the post-treatment process to a certain extent, so the method is considered together.
The inventors have surprisingly found that the loading and loss rate of the porous carbon microspheres to the complex precipitant is affected by the mesoporous size. The mesoporous size of the porous carbon microspheres in comparative examples 1 and 2 is not within the scope of the application, and as can be seen from tables 1 to 3, the loading rate of comparative example 1 is generally lower, while the standing loss rate and vibration loss rate of comparative example 2 are generally higher. Without wanting to be bound by any particular theory, based on current experimental results, the inventors believe that the mesoporous size of the porous carbon microspheres affects the load and the load firmness. When the mesoporous size of the porous carbon microsphere is smaller (for example, lower than 1 nm), the mesoporous space is relatively limited, reactants are limited to enter and exit the mesoporous, and the capability of adsorbing complex precipitate generated outside the mesoporous is insufficient, so that the overall load rate is lower. When the mesoporous size of the porous carbon microsphere is larger (for example, more than 15 nm), the mesoporous space is larger, the amount of complex precipitate generated outside the mesoporous which can be adsorbed into the mesoporous is more sufficient, the loading rate is better, but the embedding and fixing effect on the complex precipitate in the mesoporous is relatively limited, the loss rate of the porous carbon microsphere is obviously increased after the porous carbon microsphere is kept for a longer time, particularly under vibration, and the requirement of safety cannot be met. The inventor firstly notices the influence of the mesoporous size of the porous carbon microsphere on the specific application scene of radioactive element load, and the load rate of the product during manufacturing and the loss rate control level during transportation and storage are effectively improved by selecting the carbon microsphere with the specific mesoporous pore diameter range.
Claims (2)
1. A radioactive carbon microsphere, wherein the radioactive carbon microsphere comprises a porous carbon microsphere and a complex comprising a radionuclide, and the radioactive carbon microsphere is prepared by the following steps:
preparing phenolic resin microspheres: 6.4g of resorcinol, 25mL of water and 40mL of silicone oil are magnetically stirred for 5min, 5mL of sodium carbonate aqueous solution and 9mL of formaldehyde are added, the mixture is reacted for 30min under the condition of 200rpm/min magnetic stirring, the mixture is put into a reaction kettle to react for 48h at 85 ℃, the mixture is centrifugally washed for three times by deionized water and absolute ethyl alcohol, vacuum drying is carried out at 60 ℃ for 12h, and the phenolic resin microspheres are obtained after sieving; wherein the concentration of the sodium carbonate aqueous solution is 0.0616g/1000mL, and the mol ratio of resorcinol to sodium carbonate is 100:0.005; the average particle size of the phenolic resin microspheres is concentrated to 30-50 mu m;
the preparation of the porous carbon microsphere comprises the following steps: calcining the phenolic resin microsphere prepared in the above way for 4 hours in Ar atmosphere at 800 ℃ to obtain a porous carbon microsphere; wherein, in the process of heating from room temperature to 800 ℃, the heating rate is 3 ℃/min; the average particle size distribution of the porous carbon microspheres is concentrated at 25-38 mu m, and the BET multipoint specific surface area is 14.5m 2 /g, the average pore diameter of the mesopores is 6.44nm;
soaking the porous carbon microspheres in 0.3mol/L dilute nitric acid for 2 hours, sequentially washing the porous carbon microspheres with deionized water for 3 times, and drying the porous carbon microspheres to load a complex containing a radionuclide;
preparation of radioactive carbon microspheres: 0.15g of the porous carbon microsphere and the precipitant solution, YCl 3 Mixing the solutions to obtain a reaction solution, wherein the volume of the reaction solution is 3mL, and the radioactive carbon microsphere is prepared according to the following loading mode: adding porous carbon microspheres into a precipitator solution to obtain a mixed solution, standing for 12h after uniform mixing, and then adding YCl into the mixed solution 3 The solution is oscillated for 1h in a shaking table, so that the complex containing the radionuclide can be fully loaded on the porous carbon microsphere;
the precipitant solution is tartaric acid solution, and the concentration of the tartaric acid solution is 0.0167g/mL; the YCl 3 The concentration of the solution is 0.0083g/mL; the loading capacity of the radioactive carbon microsphere is 96.2%, and the static loss rate is high<0.1% and the vibration loss rate is 1.5%.
2. Use of the radioactive carbon microsphere of claim 1 in the manufacture of a medicament for treating a tumor.
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| CN202310430158.1A CN116440297B (en) | 2022-12-13 | 2022-12-13 | Radioactive carbon microsphere and its preparation method and application |
| CN202211592390.7A CN115607694B (en) | 2022-12-13 | 2022-12-13 | Radioactive carbon microsphere and its preparation method and application |
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