RU2558582C1 - Method of producing biocompatible nanoporous spherical particles of silicon oxide with controlled external diameter (versions) - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: method of producing biocompatible nanoporous spherical particles of silicon oxide includes synthesis in a reaction mixture of tetraethoxysilane (TEOS) with NH₃, water (H₂O), alcohol (C₂H₅OH) and cetyltrimethylammonium bromide (C₁₆H₃₃N(CH₃)₃Br - CTAB) in molar ratio TEOS:NH₃:H₂O:C₂H₅OH:CTAB of 1:19:370:230:0.2, with intense stirring at a rate of 125-250 min^-1 at temperature of 5-80°C for 2-3 hours to form, during hydrolysis of TEOS in an alcohol-water-ammonia medium, orthosilicic acid Si(OH)₄ monomers, condensation of the monomers to form primary particles with size of 3-5 nm, coagulation of said particles, after which the obtained particles are roasted in air at temperature of 550°C for 15 hours to remove organic substances. In another version, nanoporous silicon oxide particles are obtained by synthesis using cetyltrimethylammonium bromide C₁₆H₃₃N(CH₃)₃Br (CTAB) with concentration of up to 0.007 mol.·l^-1 as a structure-forming agent, wherein synthesis is carried out via hydrolysis of tetraethoxysilane (Si(OC₂H₅)₄ - TEOS) in a CTAB-ethanol-water-ammonia medium at temperature of 5-80°C for 2-3 hours with molar ratio TEOS:NH₃:H₂O:C₂H₅OH:CTAB of 1:19:370:230:0.2, thereby forming, in the reaction mixture, cylindrical micelles coated with a layer of SiO₂, which are organised into blocks, and then roasting the obtained materials at 550°C to remove organic substances and obtain nanopores inside the spherical particles.

EFFECT: obtaining biocompatible nanoporous spherical silicon oxide particles with a controlled external diameter, having a regular channel internal structure.

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Description

 The invention relates to the field of nanostructured biocompatible materials, in particular, to a spherical porous silicon nanocarrier.

Amorphous silica-based nanoporous materials were synthesized and studied about 20 years ago. One of the first such objects was the powder material MSM-41 [2_01,2_02]. Particles of MCM-41 of various (arbitrary) shapes and sizes have a high specific surface (up to 1100 m ² g ^-1 according to the Brunauer-Emmett-Teller method [2_01]). A typical synthesis method for MCM-41 is the self-organization of polysilicic acids in the presence of a surfactant [2_01] under hydrothermal conditions. The synthesis is carried out for two to three days in an autoclave at a temperature of 150 ° C without stirring the reaction mixture. Then the resulting material is dried and annealed at a temperature of 550 ° C to remove organic substances. The structure of the final synthesis product is a hexagonal packing of mesoporous channels, the walls of which consist of amorphous SiO ₂ [2_02,2_03]. Using various surfactants in the synthesis, it is possible to adjust the pore size from 1.6 to 10 nm [2_03]. Immediately after the discovery, these materials found wide application as catalyst supports in various industries, as adsorbents for purifying water and air from impurities, etc. [2_04,2_05]. However, these materials are not suitable for biomedical applications as drug transporting agents, since they have an arbitrary shape and particle size [2_02], which does not allow to control the kinetics of drug adsorption and desorption. In addition, materials of the MCM-41 type may have sharp edges; if they enter the body, they will have a local irritant effect.

Based on the foregoing, the authors developed a method for the synthesis of nanoporous particles with a size of 300-3000 nm, having a spherical shape, which consist of blocks of densely packed SiO ₂ nanotubes tens of nanometers in size. The synthesis conditions ensure the formation of blocks and their aggregation into particles of a spherical shape.

Under these conditions, experimental samples of porous spherical particles of silicon oxide with an ordered internal structure of nanochannels were synthesized. The pore volume is 40-60% of the total particle volume, the specific surface of spherical particles of silicon oxide is 500-800 m ² g ^-1 .

The production technology of the spherical porous structure of nanosilicon consists in obtaining biocompatible silicon nanoporous spherical particles of silicon oxide by synthesis in the reaction mixture TEOS: NH3: H2O: C2H5OH: CTAB with vigorous stirring. To remove organic substances, the resulting materials were annealed in air. Under these conditions, experimental samples of porous spherical particles of silicon oxide with an ordered internal structure of nanochannels were synthesized. The pore volume is 40-60% of the total particle volume, the specific surface of spherical particles of silicon oxide is 500-800 m ² g ^-1 .

EFFECT: method provides obtaining biocompatible silicon nanoporous spherical particles of silicon oxide with a controlled external diameter in the range of 300-3000 nm, having a regular channel internal structure. Those. The claimed method allows to synthesize porous spherical particles of silicon oxide having an ordered internal structure of nanochannels. The pore volume is 40-60% of the total particle volume, the specific surface of spherical particles of silicon oxide is 500-800 m ² g ^-1 .

The technical result is achieved by the variants of the invention: a method for producing biocompatible nanoporous spherical particles of silicon oxide with a controlled outer diameter, including synthesis in a reaction mixture of tetraethoxysilane (TEOS) with NH ₃ , water (H2O), alcohol (C ₂ H ₅ OH) and cetyltrimethylammonium bromide (C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br - CTAB) in a molar ratio of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB equal to 1: 19: 370: 230: 0.2, with vigorous stirring with at a speed of 125-250 min ^-1 at a temperature of 5-80 ° C for 2-3 hours, the formation of TEOS in the alcohol-water-ammonia during hydrolysis in an environment of orthosilicic acid monomers Si (OH) ₄ , condensation of monomers with the formation of primary particles of 3-5 nm in size, their coagulation, after which the obtained particles are annealed in air at a temperature of 550 ° C for 15 hours to remove organic substances and

a method for producing biocompatible nanoporous spherical particles of silicon oxide with a controlled outer diameter, including the production of nanoporous particles of silicon oxide using cetyltrimethylammonium bromide C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br (CTAB) with a concentration of up to 0.007 mol. l ^-1 as a structure-forming substance, and the synthesis is carried out by hydrolysis of tetraethoxysilane (Si (OC ₂ H ₅ ) ₄ - TEOS) in a CTAB-ethanol-water-ammonia medium at a temperature of 5-80 ° C for 2-3 hours at molar the ratio of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB equal to 1: 19: 370: 230: 0.2, due to which cylindrical micelles coated with a layer of SiO ₂ are formed in the reaction mixture, which are organized into blocks and then, to remove organic substances, the obtained materials are annealed at 550 ° C to obtain nanopores inside spherical particles.

For the synthesis of nanoporous spherical particles of silicon oxide, a technique similar to the Stober method used for the synthesis of nonporous silica spheres was used [2_06]. The key stages of the Stober method are the formation of primary nanometer-sized particles and their subsequent aggregation among themselves [2_07]. The monomers of orthosilicic acid Si (OH) ₄ formed during TEOS hydrolysis in an alcohol – water – ammonia medium condense with the formation of primary particles 3-5 nm in size [2_08,2_09]. The formation of primary particles is limited by the kinetics of the hydrolysis reaction, the standard deviation of the sizes of these particles is inversely proportional to their radius [2 07]. Particle size increases to 10–20 nm (depending on the concentration of reagents, pH, and temperature of the reaction mixture [2 09] and coagulation begins [2_07,2_09.2_10]. The aggregate stability of the system depends primarily on the concentration of ammonia, which determines the thickness of the double electric layer and the surface charge of the particles [2 07]. As a result, non-porous submicron SiO ₂ particles _{of a} spherical shape are formed.

Nanoporous silica particles are synthesized using the template method using cetyltrimethylammonium bromide C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br as a structure-forming substance. The synthesis is carried out by hydrolysis of tetraethoxysilane (Si (OC ₂ H ₅ ) ₄ ) in a surfactant-alcohol (ethanol) -water-ammonia medium. When the surfactant concentration exceeds the critical micelle formation concentration [2_11], cylindrical micelles are formed in the reaction mixture. At the same time, the products of TEOS hydrolysis begin to condense on the micelle surface. Due to the van der Waals forces, these cylindrical micelles coated with a layer of SiO ₂ are organized into blocks [2_12,2_13].

When a large number of such surfactant-SiO ₂ blocks are present in the reaction mixture, the system becomes aggregatively unstable, which leads to their coagulation. An approximate analytical expression for the collision efficiency of Brownian colloidal particles (SAW-SiO ₂ blocks) experiencing electrostatic repulsion of double electric layers on their surface can be written in the form of the Arrhenius equation [2_14,2_15]

where E _max is the height of the potential barrier, equal, according to the theory of DLVO, the difference between the energy of electrostatic repulsion and the energy of the van der Waals attraction of particles; k is the Boltzmann constant; T is the temperature, F is the frequency factor, depending on the concentration of particles (surfactant-SiO ₂ blocks).

In the synthesis process, the conditions necessary for the simultaneous formation of blocks of close-packed cylindrical micelles and their controlled coagulation into spherical aggregates were selected. As can be seen from the equation, temperature determines the decisive influence on the probability of particle coagulation during collisions. The attachment of the blocks to each other probably occurs with the participation of orthosilicic acid monomers (H ₄ SiO ₄ ) present in the reaction mixture.

EXAMPLE 1

A method for producing biocompatible nanoporous spherical particles of silicon oxide with a controlled outer diameter involves the synthesis of tetraethoxysilane (TEOS) with NH ₃ , water (H2O), alcohol (C ₂ H ₅ OH) and cetyltrimethylammonium bromide (C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br - CTAB) in a molar ratio of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB equal to 1: 19: 370: 230: 0.2, with vigorous stirring at a speed of 125-250 min ^-1 at a temperature of 5-80 ° C for 2-3 hours with the formation during the hydrolysis of TEOS in an alcohol-water-ammonia medium monomers of orthosilicic acid Si (OH) _4; condensation of monomers with the formation of primary particles with a size of 3-5 nm, their coagulation, after which the obtained particles are annealed in air at a temperature of 550 ° C for 15 hours to remove organic substances.

EXAMPLE 2

A method for producing biocompatible nanoporous spherical particles of silicon oxide with a controlled outer diameter involves the preparation of nanoporous particles of silicon oxide using cetyltrimethylammonium bromide C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br (CTAB) with a concentration of up to 0.007 mol. l ^-1 as a structure-forming substance, and the synthesis is carried out by hydrolysis of tetraethoxysilane (Si (OC ₂ H ₅ ) ₄ - TEOS) in a CTAB-ethanol-water-ammonia medium at a temperature of 5-80 ° C for 2-3 hours at molar the ratio of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB equal to 1: 19: 370: 230: 0.2, due to which cylindrical micelles coated with a layer of SiO ₂ are formed in the reaction mixture, which are organized into blocks and then, to remove organic substances, the obtained materials are annealed at 550 ° C to obtain nanopores inside spherical particles.

The method according to examples 1 and 2 is illustrated by the following figures for the preparation of biocompatible nanoporous spherical particles of silicon oxide.

In FIG. Figure 1 shows the change in the optical density of the reaction mixture during the synthesis of spherical particles of SiO ₂ according to the Stober method (1) and nanoporous spherical particles of silicon oxide (2).

To remove organic substances, the resulting materials were annealed at 550 ° C. During TO, nanopores formed inside spherical particles.

To register the moment of appearance of particles during synthesis, the optical density of the reaction mixture was measured (Fig. 1). To confirm the adequacy of the measurement technique used, we also studied the formation of non-porous spherical particles of SiO ₂ , which, as is known, are formed by the aggregative mechanism [2_07]. First, at a temperature of 30 ° C, a corresponding reaction mixture (without TEOS) with a volume of 0.5 L was prepared in a glass flask. After 10 min of vigorous stirring, TEOS was poured into the mixture, and this moment was taken as the reference point for the reaction time. After homogenizing the solution during stirring for ~ 0.5 min, 4 ml of the mixture was transferred into a 1 × 1 × 4 cm polystyrene optical cuvette, which was previously installed on the optical axis of the setup for measuring transmission spectra between the lens focusing the light beam, and a lens that collects transmitted light at the focal length of both lenses. The transmission spectrum of the reaction mixture was measured using an Ocean Optics 4000 spectrometer in the range of 500-1000 nm with an interval of 15 s, the recording time of one spectrum was 0.1 s. In FIG. Figure 1 shows the dependences of the optical density of the reaction mixture on the reaction time t: D = -log (T), where T is the transmission coefficient at a wavelength of 700 nm, where there are no absorption bands associated with vibrations of atoms that make up the components of the reaction mixture.

For both syntheses, the optical density does not change during the first minutes. It is likely that during this period of time in the reaction mixture the formation of surfactant-SiO ₂ blocks occurs during the synthesis of nanoporous particles or primary particles in the case of synthesis according to the Stober method. Since the size of these particles in all cases is quite small (~ 15-20 nm) compared with the wavelength of light (700 nm), the light practically does not scatter.

In FIG. Figure 2 shows an image of the outer surface of nanoporous spherical particles of silicon oxide deposited on a silicon substrate.

Subsequently, a sharp increase in optical density is observed due to the fact that, apparently, light is scattered on particles having a size comparable to the wavelength. Such a rapid appearance of large particles can be explained only within the framework of the aggregative model of the formation of nanoporous particles. Submicron particles are formed as a result of coagulation of surfactant-SiO ₂ blocks in 5-10 minutes. Due to the insufficient dynamic range of the sensitivity of the spectrometer, we were not able to fix the output of the optical density value to a constant value, however, it is clear that for all syntheses, the dependence D (t) at the end of the considered time interval becomes more gentle, which indicates that the particle growth process entered the final stage. Thus, the results of an optical experiment confirm the aggregative mechanism of the formation of nanoporous spherical particles of silicon oxide.

In FIG. Figure 2 shows the AFM image of the surface of nanoporous spherical SiO ₂ particles deposited on a silicon substrate. The average size of the spheres is 1100 nm. On the AFM image, the surface roughness of the particles is visible, which probably correlates with the block size of the close-packed silica tubes (before annealing, surfactant-SiO ₂ blocks). Chemical reagents and experiment.

The following substances and reagents were used in the work: CTAB C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br, 99%; an aqueous solution of ammonia, 24 mass. %, ≥99.99%; ethanol (C ₂ H ₅ OH), 95.7%; deionized water with a resistance of 10 MΩ and tetraethoxysilane, 99%. TEOS was subjected to fractional distillation, a fraction was selected having a boiling point T _b = 166-168 ° C. Special preparation and purification of other reagents was not carried out.

In FIG. 3 shows a diagram of an apparatus for the synthesis of nanoporous spherical particles of silicon oxide. 1 - liquid thermostat, 2 - reaction vessel, 3 - programmable mixing device.

The synthesis of nanoporous spherical particles from silicon oxide was carried out at temperatures of 5-80 ° C in a setup, the scheme of which is shown in FIG. 3. With vigorous stirring (200 min ^-1 ) the reaction mixture H ₂ OC ₂ H ₅ OH-NH ₃ -CTAB was prepared. After 10 minutes, TEOS was poured into the mixture. The optimal molar concentration of CTAB was 0.007 mol · L ^-1 , which is approximately 5 times the CMC critical concentration of micelle formation [2_11].

The molar ratios of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB reagents were 1: 19: 370: 230: 0.2. The duration of the syntheses was 2-3 hours. To remove organic substances, the obtained materials were annealed in air at 550 ° C for 15 hours.

Optimization of technological parameters of the synthesis process.

By controlling the temperature of the reaction mixture, we controlled the coagulation process, which ensured the receipt of a given final average diameter of spherical particles (Fig. 4). The average particle size was determined by dynamic light scattering. Apparently, an increase in the temperature of the reaction mixture leads to an increase in the number of nucleation centers due to faster chemical reactions in the system; therefore, from the same amounts of TEOS and surfactant, a larger number of particles with a smaller diameter are formed.

In FIG. Figure 4 shows the dependence of the average diameter of nanoporous spherical silica particles on the temperature of the reaction mixture (molar ratios of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB reagents were 1: 19: 370: 230: 0.2).

When the temperature of the reaction mixture rises above 80 ° C, the particles become non-spherical (Fig. 6), the particle diameter decreases to 95 nm. In addition, the surface roughness of the particles, probably equal to the size of the surfactant-SiO ₂ blocks (the block size, according to our estimates, is ~ 15 nm), becomes comparable with the size of the particles themselves. The non-sphericity of 95 nm particles is due to the unequal number of blocks in each particle, due to the probabilistic nature of the coagulation process. The number of blocks forming a particle is proportional to the cube of the ratio of particle and block diameters. For example, a 95 nm particle consists of only about 150 surfactant-SiO ₂ blocks, so several additional blocks that coagulated with it can significantly change its size and shape. Particles with a diameter of 400 nm (Fig. 5) already consist of 20,000 blocks with a diameter of 15 nm; the addition of several tens of blocks will practically not affect the particle shape.

SEM micrographs of nanoporous silica particles with an average diameter of 400 nm (Fig. 5) and 95 nm (Fig. 6).

The synthesis process was optimized in order to achieve the maximum value of the specific surface of the particles (Fig. 7). The specific surface of the material was calculated from nitrogen adsorption-desorption isotherms in the range of relative pressures of 0.05 ≤ p / p ₀ ≤ 0.15 according to the Brunauer-Emmett-Teller method. It is seen that the value of Ssp reaches saturation at a surfactant concentration (CTAB) equal to 0.007 mol. L ^-1 . An increase in concentration also leads to an increase in the average particle diameter (Fig. 8), which is due to an increase in pore volume. A further increase in the concentration of the reagent leads to the formation of non-spherical particles and fused (double, triple) particles. Apparently, with a constant concentration of TEOS and a gradual increase in the concentration of surfactants, there comes a time when the hydrolysis products of tetraethoxysilane are not enough to cover all surfactant micelles present in the reaction mixture. The remaining micelles can be adsorbed on the outer surface of the particles, neutralizing their surface charge, because the hydrophilic parts of the micelles are positively charged, and the surface of SiO ₂ is negatively charged. The energy of electrostatic repulsion of particles decreases, and the particles coagulate, forming aggregates of a non-spherical shape. The pore size distribution was determined based on the results of nitrogen adsorption porosimetry using the nonlocal density functional theory [2_16]. The average pore diameter was 3.0 nm.

The pore size distribution is narrow, the standard deviation is 0.15 nm (5%). The pore volume (nanochannels) was calculated from nitrogen adsorption isotherms at a relative pressure p / p0 → 1 and amounted to 40-60% of the volume of nanoporous spherical particles of silicon oxide. The indicated characteristics of nanoporous spherical silica particles satisfy the required parameters.

FIG. 7 - dependence of the specific surface of nanoporous silica particles on the concentration of CTAB (synthesis temperature 65 ° C).

FIG. 8 - dependence of the average particle diameter of nanoporous silica particles on the concentration of CTAB (synthesis temperature 65 ° C).

FIG. 9 - dependence of the electrokinetic potential of nanoporous silica particles with a diameter of 300 nm on the pH of the dispersion medium.

определяется соотношениемThe suspension of nanoporous spherical silica particles is stable in the alkaline region (Fig. 9.9) and aggregatively unstable near the isoelectric point (pH ~ 3). Based on this, the synthesis of particles was carried out with the addition of ammonium hydroxide to the reaction mixture, which increased the electrostatic repulsion of surfactant-SiO ₂ blocks. The coagulation rate decreased, the blocks were able to form the most thermodynamically favorable spherical shape during coagulation. From FIG. Figure 9 shows that the EPC value almost reaches saturation at pH ~ 11. The dependence of the hydrogen index of the medium on the concentration of ammonia $${\mathrm{<figure-callout\; id="3"\; label="C\; N\; H"\; filenames="00000007.png,00000013.png"\; state="\{\{state\}\}">C\; </figure-callout>}}_{NH}{}_3\cdot H_{2}O$$

determined by the ratio

where K = 1.76 · 10 ^-5 at 25 ° C is the dissociation constant of NH ₄ OH.

Данная концентрация аммиака является оптимальной, дальнейшее увеличение концентрации приводит к увеличению скорости процесса гидролиза ТЭОС, катализатором которого также является гидроксид аммония [2_06,2_08]. Это в свою очередь приводит к образованию непористых частиц, так как продукты гидролиза ТЭОС (мономеры Si(OH)₄) не успевают продиффундировать к поверхности цилиндрических мицелл, поэтому мономеры ортокремниевой кислоты конденсируются с образованием полисилоксанов, и, впоследствии, частиц гидратированного SiO₂.At pH = 11, we obtain that the maximum surface charge of the particles will be achieved at

This concentration of ammonia is optimal, a further increase in the concentration leads to an increase in the rate of hydrolysis of TEOS, the catalyst of which is also ammonium hydroxide [2_06,2_08]. This in turn leads to the formation of non-porous particles, since the products of TEOS hydrolysis (Si (OH) ₄ monomers) do not have time to diffuse to the surface of cylindrical micelles, therefore, orthosilicic acid monomers condense to form polysiloxanes, and, subsequently, particles of hydrated SiO ₂ .

It was found that the rate of mixing of the reaction mixture has a significant effect on the shape and size of the particles (Fig. 10). At a low stirring speed (<125 min ^-1 ), apparently, the same ratio of reagents is not achieved in the reaction mixture, local supersaturations occur. This leads to a deviation of the reagent concentrations from the optimal values, and nonspherical particles are formed. At mixing speeds> 250 min ^-1 , a turbulent mixing mode was observed, the synthesized particles were also obtained non-spherical due to the fact that both cylindrical and spherical micelles formed in the turbulent mode, which led to the formation of surfactant-SiO ₂ blocks _of various sizes and shapes.

FIG. 10 - dependence of the average diameter of nanoporous silica particles on the rate of mixing of the reaction mixture (synthesis temperature 65 ° C).

It was experimentally established that the optimal molar ratios of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB reagents are 1: 19: 370: 230: 0.2, and the stirring speed is 200 min ^-1 . A change in concentration leads to an increase in the dispersion of particle sizes, to the aggregation of submicron spheres or the appearance of particles of a non-spherical shape. The average particle diameter can be changed by varying the temperature of the reaction mixture.

Under these conditions, for primary studies, experimental samples of porous spherical particles of silicon oxide with a diameter of 300–3000 nm, with an ordered internal structure of nanochannels with a diameter of 3.0 nm (<5%), were synthesized. The pore volume is 40-60% of the total particle volume, the specific surface of spherical particles of silicon oxide is 500-800 m ² g ^-1 .

Bibliography

[1_1] O. Bisi, S. Ossicini, L. Pavesi. Porous silicon: a quantum sponge structure for silicon based optoelectronics. // Surface Science Reports 38.1 (2000), p. 1-126.

[1_2] Electrochemistry of Silicon and Its Oxide. // Xiaoge Gregory Zhang .: Kluwer academic publishers. New York, Boston, Dordrecht, London, Moscow. 2001.

[1_3] X.G. Zhang, Morphology and formation mechanisms of porous silicon. // J. Electro-chem. Soc. 151 (2004) C69-C80.

[1_4] V. Lehmann, U. Gosele, Porous Si: quantum sponge structures grown via a self-adjusting etching process. // Adv. Mater. 4 (1992) 114-116.

[1_5] V.P. Ulin, S.G. Konnikov. The nature of the processes of electrochemical pore formation in A ³ B ⁵ crystals (Part II). // FTP, vol. 7 (2007), pp. 867-877.

[2_01] Kresge S. T., Leonowicz M. E., Roth W. J., Vartuli J. C., Beck J. S. Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism // Nature. 1992. V. 359. N. 6397. P. 710-712.

[2_02] Beck JS, Vartuli J. C, Roth WJ, Leonowicz ME, Kresge S.T., Schmitt KD, Chu TW C, Olson DH, Sheppard EW A new family of mesoporous molecular sieves prepared with liquid crystal templates // J . Amer. Chem. Soc. 1992. V. 114. N. 27. P. 10834-10843.

[2_03] Zhao D., Feng J., Huo Q., Melosh N., Fredrickson G. H., Chmelka B. F., Stucky G. D. Triblock copolymer syntheses of mesoporous silica with periodic 50 to 300 angstrom pores // Science. 1998. V. 279. N. 5350. P. 548-552.

[2_04] Pham H. N., Datye A. K. Synthesis of attrition-resistant heterogeneous catalysts using templated mesoporous silica. Patent USA, N 6548440. 04.15.2003.

[2_05] Schluter R. D., Perry L. Application of mesoporous molecular sieves as selective smoke filtration additives. Patent USA, N 2005/0268925. 12/08/2005.

[2_06] Stober W., Fink A., Bohn E. Controlled growth of monodisperse silica spheres in the micron size range // J. Colloid. Interface Sci. 1968. V. 26. P. 62-69.

[2_07] Van Blaaderen A., van Geest J., Vrij A. Monodisperse colloidal silica spheres from tetraalkoxysilanes: Particle formation and growth mechanism. // J. Colloid. Interface Sci. V. 154. N 2. P. 481-501.

[2_08] LaMer V. K., Dinegar R. H. Theory, production and mechanism of formation of monodispersed hydrosols.// J. Am. Chem. Soc. 1950. V. 72. P. 4847-4854.

[2_09] Masalov V. M., Sukhinina N. S., Kudrenko E. A., Emelchenko G. A. Mechanism of formation and nanostructure of Stober silica particles. // Nanotechnology. 2011. V. 22. P. 275718.

[2_10] Matsoukas T., Gulari E. Monomer-addition growth with a slow initiation step: A growth model for silica particles from alkoxides. // J. Colloid. Interface Sci. 1989. V. 132. N. 1. P. 13-21.

[2_11] Surfactants. Reference // Under. ed. A.A. Abramzon and G. M. Gayevoy. Authors: Abramzon A. A., Bocharov V. V., Gaevoy G. M., Mayofis A. D., Mayofis R. M., Matashkina R. M., Skvirsky L. Ya., Chistyakov B. E., Schulz, L.A.: Chemistry, 1979. 376 p.

[2_12] Tan B., Rankin S. E. Interfacial Alignment Mechanism of Forming Spherical Silica with Radially Oriented Nanopores. // J. Phys. Chem. B. 2004. V. 108. P. 20122-20129.

[2_13] Zhao D., Feng J., Huo Q., Melosh N., Fredrickson G. H., Chmelka B. F. Stucky G. D. Triblock Copolymer Syntheses of Mesoporous Silica with Periodic 50 to 300 Angstrom Pores. // Science. 1998. V. 279. P. 548-552.

[2_14] Ruckenstein E., Prieve D. C. Rate of Deposition of Brownian Particles under the Influence of London and Double-Layer Force // J. Chem. Soc. Faraday Trans. 1973.V. 69.P. 1522-1530.

[2_15] Spielman L. A., Friedlander S. K. Role of electrical double-layer in particle deposition by convective diffusion. // J. Colloid. Interface Sci. 1974. V. 46. P. 22-31.

[2_16] Jaronec M., Kruk M., Olivier J. P., Koch S. A new method for the accurate size analysis of MCM-41 and other silica-based mesoporous materials // Stud. Surf Sci. Catal. 2000. V. 128. P. 71-80.

Claims (2)

1. A method of producing biocompatible nanoporous spherical particles of silicon oxide with a controlled outer diameter, including synthesis in a reaction mixture of tetraethoxysilane (TEOS) with NH ₃ , water (H ₂ O), alcohol (C ₂ H ₅ OH) and cetyltrimethylammonium bromide (C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br - CTAB) in a molar ratio of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB equal to 1: 19: 370: 230: 0.2, with vigorous stirring at a speed of 125 -250 min ^-1 at a temperature of 5-80 ° C for 2-3 hours to form during hydrolysis of TEOS in an alcoholic-aqueous-ammoniacal medium orthosilicic acid monomers, Si (OH) _4, capacitor ation of the monomers to form a primary particle size 3-5 nm, their coagulation, after which the obtained particles were calcined in air at 550 ° C for 15 hours to remove the organic substances. 2. A method of producing biocompatible nanoporous spherical particles of silicon oxide with a controlled outer diameter, including the production of nanoporous particles of silicon oxide using cetyltrimethylammonium bromide C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br (CTAB) with a concentration of up to 0.007 mol · l ^-1 as a structure-forming substances, and the synthesis is carried out by hydrolysis of tetraethoxysilane (Si (OC ₂ H ₅ ) ₄ - TEOS) in CTAB-ethanol-water-ammonia medium at a temperature of 5-80 ° C for 2-3 hours at a molar ratio of TEOS: NH ₃ : H ₂ O: C ₂ H ₅ OH: CTAB equal to 1: 19: 370: 230: 0.2, due to why cylindrical micelles coated with a layer of SiO ₂ are formed in the reaction mixture, which are organized into blocks, and then, to remove organic substances, the obtained materials are annealed at 550 ° C to obtain nanopores inside spherical particles.

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