Device and method for preparation of nanoparticles on continuous basis

FIELD: nanotechnology.

SUBSTANCE: device (50) for preparation of nanoparticles on a continuous basis comprises the first feeding device (1a) with the first feeding load (9) connected to the source (7) of the starting material, the first reactor (2) comprising the first heated reaction zone (13), the second reactor (3) comprising the second heated reaction zone (15), where all the said devices are connected to the channel of the material flow successively in the said order, at least one pressure control unit (18) mounted in the said channel of the material flow, a mixer (5) mounted in the said channel of the material flow between the first reactor (2) and the second reactor (3), the second feeding device (lb) with the second feeding pump (10) connected to the source (8) of the starting material, and the second feeding pump (10) is in liquid junction with the mixer (5), the control device (22) made with the ability to control the pressure value setting with the said pressure control unit (18) and/or the temperature value of the said heated reaction zones (13 and 15). The device is characterised in that after each heated reaction zone (13) in the channel of the material flow the appropriate cooling device (14, 16) is mounted for reducing the size of the nanoparticles in the process of their preparation, and the cooling devices (14, 16) are additionally made with the ability to cease this process of nanoparticles preparation. Also the invention relates to use of the device for preparation of nanoparticles/nanoemulsions/colloidal solutions.

EFFECT: invention enables to obtain nanoparticles which properties can be modified in the course of this process.

8 cl, 10 dwg

 

The technical field to which the invention relates.

The present invention relates to a device for producing nanoparticles in a continuous mode, which contains the first feeder which is connected to the channel of movement of the material, and at least one reactor, which has a heated reaction zone, in the same cascade.

The level of technology

It is known that nanoparticles are objects that have a size of the order of nanometers, and occupy a boundary position between atoms, molecules and bulk matter, which is built from them. With decreasing size of the particles of macroscopic materials, their properties can change significantly when the particle size approaches the values of the order of nanometers, as in this case the number of atoms on the surface cannot be considered negligible compared with the total number of atoms.

Properties of the matter in the size range of the order of nanometers are of great interest from a scientific point of view, and from the viewpoint of industrial use. However, while the properties of matter at the macroscopic scale does not depend on its size, properties of nanoparticles in most cases considerably depend on their size. For this reason, there is a serious need for the development of such devices and processes that provide the opportunity to quickly and reliably to synthesize nanoparticles of various types, with different structure, and with a narrow distribution of particle sizes. In this case, "different structure" refers to nanoparticles constructed from a single component (monostructure nanoparticles), two or more components (composite nanoparticles). One sub-group composite nanoparticle is a nanoparticle with the structure of "core-shell", in which one or more components form the core of the nanoparticles, and one or more components to form the shell (coating) around the nucleus.

Now for the synthesis of nanoparticles are used as reactors, batch, and continuous reactors actions. Reactors periodic operation more economical than the larger size party. On the other hand, increasing the batch size leads to a less homogeneous distribution of particles sizes.

A simple reactor for the synthesis of catalysts in situ is described in the publication Microfluid Nanofluid 2008, 5, 411-416. System tubular microreactor continuous action described in nano-letters 2004, 4(11), 2227. This system is used only to obtain silver nanoparticles. Synthesis of silver nanoparticles is also carried out by the device disclosed in the patent application U.S. 2005/0179175. Particles obtained from the vapor source reagent.

From the literature it is also known that in pharmaceutics and industrial the tees are faced with the problem of low water solubility of active pharmaceutical ingredients (API, Active Pharmaceutical Ingredients) and biologically active molecules. To increase the solubility in the classical formulations of drugs used in a manner ultrafine grinding ("micronization"). The size of the particles obtained by these methods varies from 2 to 5 μm. In some cases, micronizing does not lead to an effective increase solubility, and does not solve the problem of low bioavailability. Further reduction of particle size to the range of nanometers can give the solution of this problem.

Technology, with which it is possible to obtain nanoparticles of drugs can be divided into two groups: the rising of the deposition of nanoparticles from the solution) and the descending type (reducing the size of particles obtained by micronization to sizes of the order of nanometers). In a typical case, the size of the nanoparticles is less than 1 micron.

Two technologies descending type, which are widely used in the pharmaceutical industry, this high-pressure homogenization (see Dissocubes®: U.S. patent 5858410 or Nanopure: PCT/EP00/06535, and Nanoedge™: U.S. patent 6884436) and grinding (see Nanocrystal™: U.S. patent 5145684). These methods peculiar to the following disadvantages. None of them allows the nanoparticles continuously; material requires pre-treatment (mi is anizatio); optimization of parameters of the reaction is difficult and requires a lot of time. These methods require a large amount of material, thus, they cannot be used at the stage of drug development (or can, but only with high costs). Grinding requires large amounts of energy, therefore, such systems must be cooled. When grinding due to thermal effect can be changed crystal structure. Working with nanobelt (particles smaller than 250 nm) dangerous and requires compliance with special safety rules.

Technology ascending type (see Hydrosol: patents great Britain 2269536 and 2200048 or U.S. patent 6607784) for nanoparticles in the pharmaceutical industry are not used, since it is difficult to perform stable control of obtaining particles of uniform size. Control of deposition is difficult and optimization of parameters of the reaction requires more labor and time. Also known and some system of continuous actions, which allow to obtain metallic nanoparticles in the amount of micrograms due to chemical reactions. However, such reactors can usually be used to obtain nanoparticles containing only one metal. Moreover, the range of applicable solvents narrow because of the known reactors complianc the aqueous actions operate at atmospheric pressure, and thus, the boiling point of the solvent limits its application for the case of nanoparticles, when you want a certain temperature for their synthesis.

In U.S. patent 6179912 described a microfluidic system reactor continuous action to obtain the fluorescent nanoparticles. The system contains two reactor cascade is switched on. The reactor can be heated to different temperatures, but the possibility of filing a new solution of the reagent in the point between the two reactors is missing. The mixture of reagents is carried out before entering the first of the heated reactor module, thus, this system of reactors can be used for the synthesis of such multicomponent nanoparticles, in which the distribution of components within the nanoparticles is uniform or random. Therefore, in this system it is impossible to obtain nanoparticles with the structure of "core-shell". The size of the obtained nanoparticles is due to the length of the heated reactor module, however, to change this setting in the reaction is difficult, and thus, this system reactors usually can be optimized for the synthesis of one type of nanoparticles. An additional disadvantage is the limitation on the boiling temperature of the solvent, since the system operates at atmospheric d is no. Thus, it is possible to use only solvents that at the reaction temperature remains in liquid form, i.e. it is usually organic solvents with high boiling point.

Disclosure of inventions

The present invention is to overcome the problems and disadvantages inherent in the devices current level of technology, especially in the direction of create devices with continuous actions and processes for the synthesis of nanoparticles, in which the properties of the obtained nanoparticles can be modified during the process by modifying/optimizing operating parameters of the device together with the parameters of the process in order to obtain nanoparticles with desired structure and properties.

Secondly, the task of the invention, the change of the size of the synthesized nanoparticles during their synthesis is solved by a device operating in a continuous mode.

According to the invention the above problem, the change of properties of the synthesized nanoparticles during their synthesis is solved by a device for nanoparticles in the system operating in continuous mode, which contains the first feeder which is connected to the channel of movement of the material, and at least one reactor, which has a heated reaction zone, in the same cascade.

Still the way the subject invention is a system 50 operating in a continuous mode, for the synthesis of nanoparticles, which contains the device 1a filing, coupled with the channel of movement of the material, at least one first reactor 2, which has a heated reaction zone 13, the second reactor 3, which is in the same cascade follows the first reactor 2; the mixer 5 and the second device 1b filing between the first reactor 2 and the second reactor 3; supply pumps 9 and 10 connected to the source of the source material, and/or device 22 of the control is arranged to control at least one regulator 18 pressure and/or temperature of at least one of the heated reaction zone 13, when each of the heated reaction zone 13 in cascade set the cooling unit 14.

Corresponding to the invention the device comprises a cooling device 14, which is located in the cascade after a heated reaction zone 13, while the reaction zone 13 with the device 14 is fixed in the reactor 2.

According to a preferred variant of the invention, the system includes a device 4 analysis of the final product, which is located in the channel of movement of the material after the final reactor (3) and contains the analyzer dynamic light scattering Dynamic Light Scattering, DLS).

In addition, predm the fact of the invention is the use of the above-described device for the synthesis of nanoparticles of one, two or more components, preferably metals, nanoparticles, nanoemulsions, nanosuspensions and colloidal solutions containing biologically active organic molecules, and nanoparticles with the structure of "core-shell".

In accordance with a preferred embodiment of the invention, the system is suitable for the synthesis of nanoparticles of active pharmaceutical ingredients (API).

The invention also relates to a method for producing nanoparticles, preferably nanoparticles containing metals or biologically active organic molecules, using the above device.

According to a preferred variant implementation of the method applied to molecules non-steroidal anti-inflammatory substances, medicines used to treat erectile dysfunction/pulmonary hypertension, compounds stanovova series of statins and protivogistaminnyh compounds, and the synthesis is performed in the system operating in continuous mode.

The synthesized nanoparticles are subjected to analysis to determine the level of required properties, if required, the process parameters can be changed. This parameter is the temperature of the heated zone of the reactor (reaction zone). A well-known effect of high temperature is what is this temperature increases the reaction rate, which in turn speeds up the synthesis process. A relatively wide range of applicable temperatures (10°C-350°C) allows to synthesize different types of nanoparticles, which makes the considered reactor General purpose tools for nanoparticle synthesis. However, increasing temperature can lead to boiling of some solvents source of the liquid feeding device feeds in a heated reaction zone, where the solvent evaporates and the dissolved material precipitates. In the existing flow systems with continuous movement of the material deposition prevent choosing a solvent whose boiling point is sufficiently high compared with the planned temperature in the reactor. However, this leads to the impossibility of a significant temperature change in the reactor during the process in accordance with the current results of the analysis of the obtained nanoparticles. If the temperature that is used in the reactor, does not provide the required properties of the nanoparticles, the synthesis scheme has to be reviewed, in some cases, choosing raw materials other solvent, which significantly increases the time required for reaction optimization.

The advantage of the device corresponding to the present invention, is that the course of the synthesis can be modified and they can upravlat is in the process of the synthesis, because the system provides greater flexibility with respect to the source of fluid containing one or more source materials. In this case, "the source fluid" generally refers to the source reagent solution or (this will be more discussed below) reusable colloidal solution in which the raw materials required for the synthesis of nanoparticles are present in dissolved or dispersed form. The main part of the source liquid may be a solvent or carrier liquid, which does not dissolve the starting material, used for synthesis of nanoparticles. In this description for simplicity mainly uses the term "solvent", but the facts mentioned in relation to "solvents"obviously also applicable to the "carrying liquids".

In the case of current flowing systems (systems with continuous movement of the material), the solvent, which is the main part of the original liquid, it is necessary to choose in accordance with the reaction temperature required for the synthesis of nanoparticles. Thus, in the reactor, which correspond to the current state of this technology, solvents with a low boiling point (carrier liquid) cannot be used. This restriction does not apply to the device corresponding to the present image is ateneu, because by increasing the pressure in the reaction zone, the boiling point of the used solvent can be raised so that it always remained higher than the temperature of the reaction zone, i.e. the solvent was never boil. Thus, the use of high pressures (1-250 bar) significantly expands the group of solvents that can be used, the yield of the reaction product can be increased significantly without unwanted deposition.

According to the invention, examples of solvents with a low boiling point (volatile) can be used: methanol, ethanol, propanol, isopropanol, ether, dichloromethane, chloroform, toluene, acetone, water and mixtures of these solvents (solvents with a low boiling point are not limited to the above list).

In addition to the above advantages, due to the common use of high pressure and temperature can be achieved supercritical state of the solvent used. That is, a condition in which the properties of the original fluid still subject to study, and it is possible to increase the yield of the reaction product. Thus, corresponding to the invention, the device allows to synthesize nanoparticles in supercritical conditions state that opens new horizons in the study of nanoparticles and their synthesis.

Using soo is relevant to the invention the device can also be a reliable way to synthesize nanoparticles API size of several nanometers. Consumption material flow system continuous minimum, therefore, this system solves the problem of "ninaithale" biologically active molecules even at the stage of drug development. Because ninaithale heat is absent, the risk of structural adjustment of the synthesized nanoparticles is minimal. The nanoparticles synthesized using the device corresponding to the present invention, are obtained in the form of colloidal solutions, nanoemulsions or nanosuspension, and, thus, strict rules nanobelt to the device do not have a relationship.

Corresponding to the invention the device may contain analyzer dynamic light scattering in the material flow (mass analyzer), which allows continuous monitoring and control of the size of the synthesized nanoparticles during the synthesis. In the case of other known devices do not permit this.

The objective of the invention consisting in changing the size of the synthesized nanoparticles during the synthesis, is solved by running device with continuous movement of the material, which contains the first feeder which is connected to the channel of movement of the material, and at least one first reactor and one second reactor. An important part of the device is will smeet is l, located between the two reactors, and the second feeder which connects with the channel of movement of the material through the mixer. The role of the second feeder consists of the delivery of the second source of fluid to change the specified properties of the intermediate product coming from the first reactor.

The second feeder allows you to add another reagent in the nanoparticles, synthesized the first reactor. In the result, the properties of the nanoparticles, leaving the first reactor can be modified in the second reactor. For example, on the surface of the nanoparticles is possible to create a coating that modifies the properties of the nanoparticles, or in controlled conditions to synthesize multi-component or multi-functional materials.

Similarly, setting after the second reactor reactors and attaching the drawer to the channel of movement of the material through the mixer, placed between each pair of reactors, the resulting nanostructures can be modified again and again in each additional reactor, so that it was possible to synthesize nanoparticles containing multiple layers of coating on the core, which is formed in the first reactor.

In this case, the settings can also be adjusted in situ. Analyzing nanocat the Itza, leaving the second reactor, it is possible to get information about the homogeneity of the coating, the ratio of the core material and the coating; and you can also change the parameters of the process (the temperature of the reaction zones of the first and second reactors, the feed speed of the first and second source of fluid and the like) during the reaction.

In accordance with a preferred embodiment of the device and method of the present invention, the final product that comes out of the last reactor, is subjected to optical analysis method, and in accordance with the results of this analysis can be adjusted to some specific parameters of the device and the process for the current reaction. For example, using a flow cell together with the spectrophotometer in the UV and visible region (UV/Vis) or stream analyzer, dynamic light scattering, it is possible to conduct a qualitative flow analysis of nanoparticles in the final product.

Brief description of drawings

Embodiments of the present invention will be described in more detail below with reference to the accompanying drawings, on which:

figure 1 depicts a block diagram of the preferred alternative implementation of the device corresponding to the present invention;

figa-2c represent THE image (transmission electron microscope) Pt nanoparticles with different / min net is the beautiful flow of the source material;

fig.2d depicts the dependence of the average size of the particles from the flow rate of the source material;

figure 3 represents THE image of bimetallic nanoparticles of Pt-Fe;

figa is THE image of CdSe nanocrystals;

fig.4b represents the radiation spectra of colloidal solutions of CdSe nanocrystals synthesized at different flow velocities of the source material.

figure 5 depicts the distribution of the particles of ibuprofen in size obtained by measuring light scattering (example 4);

6 is an x-ray diffraction pattern for ibuprofen (example 4);

Fig.7 depicts the distribution of nanoparticle sizes for different ratios of SD-carbopol (example 5);

Fig depicts the distribution of nanoparticle sizes for different amounts of added polyethylene glycol (example 6);

Fig.9 depicts the distribution of nanoparticle sizes for various amounts of added polyvinyl-pyrrolidone (example 7);

figure 10 (table 1) represents the average size of the Pt nanoparticles obtained in experiments with air cooling and a counterflow heat exchanger.

The implementation of the invention

Figure 1 presents the block diagram of the preferred alternative implementation of the device 50 corresponding to the present invention. The device 50 is a laboratory device is in flow type (continuous movement of the material) for the synthesis of nanoparticles, which operates in a wide pressure range (1-250 bar) and temperatures (10-350°C), and includes the first device 1a supply and the second device 1b filing; the first reactor 2 and the second reactor 3, is included in the same cascade as the device 1a, the device 4 collection and analysis of the product, which is included after the reactors; the mixer 5, which is connected to the device 1b through the check valve 6, and is located between reactors 2 and 3; and the device 22 of the control.

Devices 1a and 1b filing contain source material for the synthesis of nanoparticles in the case under consideration, the tanks 7 and 8 of the source material. The original liquid, which contains the source material or materials may be introduced through a line connected to the device 1a or 1b filing; in this case, this line serves as a source of raw materials. Devices 1a and 1b filing also contain feeding pumps 9 and 10, and appropriate gauges 11 and 12. Usually the source of fluid represent solutions or colloidal solutions, thus, as the supply of pumps 9 and 10 can be any suitable liquid pumps. The required flow rate, typically in the range of 0.1 to 10 ml/min, can be set via a supply pump 9 and 10. For example, isocratic pumps Knauer® for high-performance liquid chromatography (HPLC), the nature of soumise maximum working pressure of 400 bar and a performance in the range of 0.01-10 ml/min, can serve as feed pumps 9 and 10. At a flow rate of 5 ml/min, their error is less than 2%. These pumps are widely used for washing HPLC columns, for liquid samples increased volume, and to transfer allentow to meet the pressure.

Reactors 2 and 3 contain the heated reaction zone 13 and 15, which in the direction of travel of the material followed by cooling devices 14 and 16. The reaction zone 13 and 15 in the preferred case are resistant to temperature and pressure coils operating in continuous flow, in which the temperature of the reaction mixture is controlled thermal environment up to a temperature of 350°C. is Desirable, the use of thermally conductive heating elements type coil with electric heating, for example, coiled heating elements VICI® type Hastelloy C. In this case, the outer tube diameter is 1.6 mm with an inner diameter of 0.8 mm, the Length of the portion of the reaction zone 13 and 15, where the control temperature is 3200 mm, power for heating 144 watts, and current consumption 12 A. the Temperature can be controlled and adjusted to 350°C±1°C.

The cooling device 14 and 16 represent a counter-current heat exchangers, in which the hot medium emerging from the heated reaction zones 13 and 15, communicates what about the counter-moving environment having a room temperature. The heat exchangers contain tubes welded to each other with hard solder. This can be, for example, tube type Hastelloy C, manufactured by VICI®. The outer diameter of this tube is 1.6 mm and an inner diameter of 0.8 mm, the effective length of the heat exchangers is 1200 mm

The mixer 5, which is located between the first and second reactors 2 and 3, may be any passive or active mixing device. One of the most simple passive mixing elements is a tee, providing merge threads. The second source fluid from the device 1b filing through this tee connects to a solution of the product coming from the reactor 1. The mixer 5 is convenient to use ground stainless steel element type VICI®. Such a mixer 5, for example, has a bore diameter of 1 mm, however, you can attach a tube with an outer diameter of 1.6 mm

The flow of matter in the direction from the mixer 5 to the second device 1b filing preferable to delete by selecting the check valve 6 (for example, stainless steel valve from ThalesNano Inc., Budapest), working in the pressure range from atmospheric to 250 bar. It is desirable that the check valve 6 was chemically resistant against aggressive media, and thus it can be used with any is the home of the original liquids.

The device 4 designed for the collection and analysis of reaction products in this design contains a pressure gauge 17, the pressure regulator 18, the flow cell 19, a flow analyzer, in particular, the optical detector 20 and the reservoir 21 of the product.

In the device 50, the pressure control is carried out based on the data from the pressure gauges 11, 12 and 17 by means of the controller 18 of the pressure-driven device 22. As pressure gauges can be used device type Knauer®, originally developed for HPLC, with a working pressure up to 400 bar.

As the regulator 18, the pressure can be, for example, the control valve pressure (development company ThalesNano Inc., Budapest), suitable for precise control of high pressures in devices operating with high values of bulk feed, such that are used in tasks liquid chromatography high pressure.

Preferably, the device 50 can be combined with a flow detector 20, which may represent, for example, spectroscopic device (used in the example below 3 for the continuous analysis of semiconductor nanocrystals type CdSe). In this case, as a light source was used led type USB-LS-450, emitting at a wavelength of 465 nm. The detector can use isometsa, for example, small USB2000 spectrometer, equipped with CCD sensor operating in the range from 200 to 1100 nm, or measuring dynamic light scattering (Nanotrac, measuring light scattering, equipped with a laser led with a capacity of 3 mW at a wavelength of 780 nm; a range of measurement wavelengths: 0.8 to 6500 nm), suitable for in-line determination of particle size and distribution of particles sizes in the cases of various nanoparticles (see examples 6 and 7).

The device 22 of the control, in the preferred embodiment, is connected with all devices and controls all devices that carry out the regulation of any of the operating parameters or measure operating parameters. These devices include the supply pump 9, the gauges 11, 12 and 17, the controller 18 of the pressure device of heating the reaction zones 13 and 15, the cooling device reactors 2 and 3. The device 22 of the control, in the preferred embodiment, consists of a control electronic device 23 and the device 24 data entry and display, through which the operator can manually set the desired operating parameters of the device 50, such as flow rate of the first and second charge pumps 9 and 10, the pressure and temperature in the reaction zones 13 and 15 of the first reactor 2, and, accordingly, the second reactor 3.

It should be noted that in case the device presented in figure 1, the control pressure is made at one point by means of the controller 18 of the pressure, so the pressure is the same throughout the cascade. However, at other points can be equipped with additional controllers 18 pressure, whereby it is possible to set different pressures in the reaction zones 13 and 15.

The method proposed in the present invention, is implemented by the device 50 corresponding to figure 1, which works as follows.

Solutions containing original compositions and coming from the device 1A of the feed into the reactor 2 at the proper pressure and flow through the reaction zone 13, is heated to the appropriate temperature, with the rate of flow is controlled by the supply pump 9. The time spent in the reaction zone 13, is determined by the flow rate, therefore, the supply pump 9 controls the reaction time in the reaction zone 13. The reaction time is set so that the required reaction could be completed, and received the first intermediate product. In the cooling device 14 of the reactor 2, the intermediate product is cooled to the desired temperature, and then connected and mixed in the mixer 5 with the second source liquids (chemicals)coming from the device 1b filing, and together they enter the reactor 3, where, similarly to the previously described which, some further reaction in a controlled manner. Reactions that take place in reactors 2 and 3, include particle formation and growth. In this scheme corresponding to the invention, the device 50 is a system of coupled reactors, in which the synthesis of nanoparticles. The final products are analyzed in a flow cell 19 through a flow detector 20, and is collected in the tank 21 of the product.

The device 22 management manages the feed pumps 9, 10 and the regulator 18 pressure by means of the parameters specified by the operator and/or on the basis of data measured or collected by the devices connected to the device 22 of the control; the device 22 controls the temperature of the reaction zones 13 and 15 and cooling devices 14, 16, providing, thus, the required flow rate, pressure and temperature.

It is desirable to have the possibility of regulating the temperature of the reaction zones 13 and 15 from 10°C to 350°C. Through the use of charge pumps 9 and 10, pressure gauges 11, 12 and 17, as well as managed regulator 18 pressure corresponding to the invention, the device 50 is also suitable for performing reactions at pressures up to 350 bar. Liquid pumps 9 and 10 are able to provide throughout the system flow rate on the 10 ml/min

At the end of the synthesis process the entire quantity of the used solvent and chemicals can be collected, if necessary, destroyed, or disposed of, for example, if you want, it can be reused in the reaction, other device, or corresponding to the invention the device 50 (i.e. reused); thus, the whole procedure is environmentally safe.

The two-reactor device 50 allows the implementation of different reactions in the reaction zones 13 and 15, which are well separated reaction chambers. The cooling device 14 and 16 are attached to both reaction zones 13 and 15 directly, allowing immediate cooling of the reaction products after their release from the reaction zones 13 and 15, and thanks to immediate termination reactions (synthesis). Thus, there is a possibility of reliable control of temperature and reaction course, and the device is suitable for nanoparticles in the form of monodisperse systems, i.e. the distribution of the synthesized particles is narrow, for example, 1-3 nm in the case of metal particles. However, the width of the distribution can be precisely controlled due to the exact parameters of the reactions. In particular, the device 4 for the collection and analysis of reaction products, coupled with the RB reactor 3, includes device flow analysis, for example, the optical detector 20, which is designed with the ability to analyze the quantity and quality of the end product for a short time (30 sec).

If you want to use the reaction products (typically a colloidal solution of nanoparticles)leaving the reactor 2, as the original liquid for the subsequent reactions in the second reactor 3, and require the addition of an additional reagent or solution, this new reagent (solution) can be entered into the system through the mixer 5. Feed solutions into the reaction zone 15 is controlled by a check valve 6.

By means of the device 24 and data entry display part of the device 22 of the control, you can set the flow rate, and the values of temperature and pressure. The control electronic unit 23, on the one hand, connected to the device 24 data entry and display, and, on the other hand, with feed pumps 9 and 10, the heating devices of the reaction zones 13 and 15, the cooling units 14 and 16 gauges 11, 12 and 17, the controller 18 pressure, and (if required) with the line detector 20. The appointment of an administrator of the electronic device 23 to provide the values of the flow rate, temperature and pressure, which had been previously set, and if you want to display the results of measurements made poto is the principal detector 20, in the appropriate form. On the basis of continuous analysis of some properties, for example, the size of the Produced nanoparticles, the device 22 of the control can automatically adjust the operating parameters of the device 50, or the operator can change the values of one or more parameters in order to obtain the required properties. If properties depend on particle size, a variable parameter is usually the flow rate or temperature. In both cases, both may be necessary and proper pressure setting. For example, in particular, by increasing the temperature in the reaction zones 13 and 15 is reached boiling point of the solvents used for the source of liquids, and in this case, the device 22, the control will automatically increase the pressure in accordance with the schedule of dependence of boiling point on pressure for a given solvent (set in advance), in order to keep the boiling point of the solvent above the temperature of the reaction zones 13 and 15.

In the preferred case, the electronic control device 23 consists of one or more microcontrollers or one or more computers that are suitable for administration in real time, or from a combination of these two devices.

The device 24 of the display and data entry can represent with the second device with any principle of action, suitable for displaying a wide range of characters or graphic information (light-emitting diodes, liquid crystals, and the like, a display or a cathode-ray device, a liquid crystal display or other display type). The input device may be either specialized, consisting of individual buttons, or it may be a standard keyboard or touch screen.

In the implementation of the method proposed in the invention, it is possible to synthesize nanoparticles of noble metals, preferably gold (Au), platinum (Pt), palladium (Pd), ruthenium (Ru), rhodium (Rh), iridium (Ir), semiconductors (CdSe) and magnetic nanoparticles (Co, Fe2O3). Using the device shown in figure 1, it is possible to obtain complex nanoparticles by using two initial solutions, for example, nanoparticles of alloys or composite material of the above metals or nanoparticles with the structure of "core-shell", or nanoparticles combinations of the above elements (metal-semiconductor, magnetic-semiconductor, metal-magnetic).

The interval sizes of the particles of the final product is 1-10 nm and can be selectively changed. Applications of the obtained nanoparticles can be the following: solar cells, the Assembly of microelectronic circuits, laser technology, the creation of the LEDs, as well as biomedical sphere of the application, such as diagnosis research cancer.

The application device 50, shown in figure 1, for the synthesis of nanoparticles of different types will be demonstrated below, the application corresponding to the invention are shown below examples are not limited.

Applied methodology: synthesis of metals in the liquid phase by means of their recovery in the presence of alcohols at high temperatures, and obtaining metals from metal ions by recovery in the presence of, for example, hydrogen, hydrazine, borohydride or alcohols in accordance with the reactions described in the literature.

Preparation of the starting solution: metal-containing reagent (e.g., any platinum salt) dissolved in any alcohol, preferably in ethanol or methanol in the presence of a stabilizing substance (of any polymer, preferably polyvinyl-pyrrolidone). The stabilizing substance is administered to prevent aggregation of the nanoparticles formed during the reaction.

In the first embodiment of the application device 50 is used to produce the nanoparticles of the same metal as follows.

The initial liquid (reagent solution) is placed in the reservoir 7 to the source of fluid, where the supply pump 9 pumps it into the first reactor 2. In the case of the synthesis of nanoparticles of the same metal, it is necessary only device 1a of the feed (i.e. the device, consisting of a tank 7, the original liquid, the feed pump 9 and 11 gauge) and only one reactor, such as reactor 3. By means of the feed pump 9 source fluid pumped through the reactor 2, the reactor is no reaction does not occur; the reaction zone 13 is not heated - it remains at room temperature. The mixture is then fed to the second reactor 3 through the mixer 5 (ground item), while the branch that leads to the second device 1b filing, closed non-return valve 6. Reaction zone 15 in the second reactor 3 is heated to a temperature corresponding to the actual reaction, therefore, there occurs the reaction of recovery: alcohol restores metal ions to the metal. The stabilizer based on the polymer, which at a given temperature resistant (no decomposition), prevents aggregation of the nanoparticles of the metal due to the effect of steric stabilization. The cooling device 16, which in this stage follows the reaction zone 15, quickly cool the solution to room temperature, thereby inhibiting undesirable continuation of the reaction. Thus, the size of nanoparticles can be easily controlled, properly setting the flow rate and temperature. The reaction product is a colored colloidal solution, the color of which depends on the nature of IU is Alla and particle size, for example, the color may be brown (in the case of noble metals) or, for example, greenish-red (in the case of CdSe). In the process of synthesis of semiconductor nanoparticles, as flow analyzer can be applied to an optical analyzer, preferably a spectrophotometer or measuring dynamic light scattering detector (20), because in this case, the optical properties of the obtained colloidal solution to a large extent depend on the contained nanoparticles. The semiconductor nanoparticles (e.g., CdSe), depending on its size, absorb and emit light at different wavelengths. However, in the process of synthesis of metal nanoparticles optical analyzer does not use this way, because in this case the effect is not manifested so much. The optical detector 20 can also be used in the synthesis of nanoparticles of gold and silver, but in these cases, the absorption depends on surface plasmons (collective motion of the electron shell).

In the second embodiment, the application device 50 is used for synthesis of nanoparticles of bimetals or nanoparticles with the structure of "core-shell" as follows.

In this case, the use of both the feeder and the first device 1a and the second device 1b. Basic nanoparticles get into the first heated reactor 2, for example, from the similar liquid, contained in the tank 7, get the platinum nanoparticles. The solution of the second source material contained in the second tank 8 to the source of fluid through the supply pump 10, through the mixer 5 is injected into the reaction zone 15. If the goal is to increase the size or change the shape of the Pt nanoparticles, as a second source of fluid can again be taken solution containing platinum. Otherwise, you may be taken other metal-containing solution, for example, a solution containing iron: In the latter case, the reaction product will be a bimetallic system. Semiconductors with the structure of "core-shell" get similarly: the core semiconductor get in the reactor 2, and in the second reactor 3 particles covered with a shell, as in the case of semiconductor quantum dots of cadmium selenide/zinc sulfide (CdSe/ZnS). In this procedure, a solution of starting material required to obtain the ZnS shell, serves the second supply pump 10 through the mixer 5, which is located between the first and second reactors 2 and 3. The source material is decomposed at a high temperature reaction zone 15 of the second reactor 3, and, as the shell covers the previously formed the core of CdSe. The composites of the type CdSe/ZnS are of utmost importance in the manufacture of solar cells, p is given that have a large quantum yield, and are exceptionally stable and resistant materials.

In the case of both reactors 2 and 3 corresponding to the invention, the device 50 is also suitable for the production of metal-containing nanoparticles in accordance with the principles of combinatorial chemistry. This includes, for example, mixing of semiconductors with metals, for example, CdSe/Au, or magnetic nanoparticles: CdSe/Fe, CdSe/Co, CdSe/Fe2O3.

The second metal can be embedded into the first randomly, they can form an alloy or system structure (bimetallic system with the structure of "core-shell"), the second metal may diffuse into the first, or it may even form a layer around the first metal. It all depends on metals, raw materials, solvents or carrier liquids, and ambient conditions (temperature, pressure, flow rate), which are used for reactions in two stages. By using the appropriate invention device 50 can be implemented in practically any combination of the above options - for this reason, and reference was made to the principle of combinatorial chemistry. Thus, due to the possibility of application of hundreds and even thousands of combinations can be obtained nanoparticles that best meet your requirements.

In industry also are approx the imposition of the metal system of the three, four metals or multimetallic system (for example, in the automotive industry, noble metals Pt, Pd and Rh are used in the three catalytic converters of exhaust gases). These nanoparticles can also be obtained with the help of the device 50. To carry this out, carrying out sequential reactions, when the end products collected in the reservoir 21 of the final product, is used in the subsequent reaction as the starting materials. Another possibility is the expansion device 50 through the third feeder and reactor, and a second mixer and a second check valve, so you can add a third source fluid from the third drawer in the intermediate product leaving the second reactor 3.

The fact that it is impossible to obtain metal nanoparticles with a uniform distribution, preparing the initial solutions of two or more metals and feeding them into a single reactor, emphasizes the advantages of the device 50, in which there are two or more reactors 2 and 3. Obtain the desired result in the managed system can be achieved by using sequential reactions.

As already mentioned, the nanoparticles produced in accordance with the invention device is used directly. Of course, the resulting nanoparticles can also be the particular in solid form from their colloidal solution ways known in modern technology. For example, this can be done by a simple mixing colloidal solution with an organic solvent (preferably, for example, hexane) followed by separation or centrifugation, the precipitated particles. Again, if these nanoparticles need to re-enter in a colloidal solution, the nanoparticles obtained in solid form can be atomized in a suitable solvent. This procedure can also be used for purification of the nanoparticles.

It should be noted that the use of the present invention counterflow heat exchanger gives more reproducible results in the synthesis of nanoparticles of biologically active compounds, for example, nanoparticles of active pharmaceutical ingredients (API). In the experiments, illustrating implementation of the invention, were made obtaining nanoparticles from a solution of dimethyl sulfoxide (active pharmaceutical ingredient) by adding water as antisolvent and carbopol 980 as a reagent, forming a polyelectrolyte. Without heat exchanger, mixing dimethyl sulfoxide with water, an increase in the temperature of 5-8°C (heat of mixing). This increase in temperature leads to undesirable side reactions: sometimes to postpolymerization of carbopol 980 (derived polyacrylate, poorly sewn, aliperta what Aricom). As a result of postpolymerization, weakly cross-linked polymer mesh causes the formation of aggregates of micron size. Through the use of a heat exchanger observed in the reaction zone the temperature increase can be reduced, and thus, by controlling the temperature of adverse reactions can be excluded.

Hereinafter, examples will demonstrate operation corresponding to the invention of the device 50 and its distinctive features.

Example 1. Obtaining nanoparticles of platinum (Pt) and their optimization.

The first stage was prepared with the original solution as follows: prepared 6×10-3M solution hexachloroplatinic acid (H2PtCl6×6H2O (Aldrich) in a mixture of methanol with water (at a ratio of methanol:water = 9:1), then added to the polymer PVP (polyvinyl-pyrrolidone, Aldrich) with 10-fold excess of the monomer with respect to ions Ft4+. The role of the polymer was to prevent aggregation of the nanoparticles of Pt, that results in a synthesis (in the tank 21) turned out to be a stable colloidal solution.

In the second stage by means of the device 22 controls were set to the parameters of the reaction (temperature, pressure, and flow rate). The experiment was performed at a flow rate of 1 ml/min, the reaction temperature 150°C (in the reaction zone 13 of the first reactor 2) and a pressure of 45 bar.

Before PR is the conduct of experimental reaction system was washed with methanol, which was pumped into the reactor 2 by the supply pump 9. After checking that the system does not contain any impurities and reaction zone 13 is stably holds the settings in the reservoir 7 to the source of fluid put the initial solution and turned on the pump supply. When mentioned flow rate of 1 ml/min it took 5 min to the first drops of the synthesized colloidal solution appeared in the tank 21 of the product. Due to the constant and systematic changes of the parameters of the reaction can quickly realize the optimization of the synthesis of Pt nanoparticles in size. In the synthesis process, the flow rate was varied in the range from 0.2 to 3 ml/min, with the resulting colloidal solutions were collected in separate tubes. Analysis of samples was performed on a transmission electron microscope (Philips CM 20 THEMES). The distribution of nanoparticle size was determined on several hundred particles by counting manually.

The results presented in figa-2d. On figa-2c shows the image in the Pt nanoparticles synthesized at different flow velocities: figa - 0.2 ml/min, fig.2b 1 ml/min, and figs - 3 ml/min To fig.2d shows the dependence of mean particle size on the speed of the stream.

Analysis of particle size by using THE clearly shows a narrow distribution of nanoparticle sizes, as well as the possibility of a simple and t is ncoi settings distribution of particle size by changing the parameters of the reaction (in this case - flow velocity). The particle size of Pt increases with decreasing flow rate, as metal ions that are in the initial solution, spend more time in the heated reaction zone, which leads to a higher probability of aggregation of newly formed nuclei of the crystals and causes the appearance of larger nanoparticles. At higher flow rate the time interval provided for the growth of nanoparticles becomes shorter.

Conclusions: by using the appropriate invention device 50 and corresponding to the invention may be synthesized Pt nanoparticles quite certain size, for a short time, approximately grams. When stored at room temperature, the obtained colloidal solutions every time demonstrated stability - aggregation of nanoparticles was observed. Due to the characteristics of the device 50 optimization of the process in relation to the size of the particles can be performed in a short time.

Systematic variation of the flow velocity in the synthesis process has led to the fact that the size of the particles in each of the samples taken from the product was in the range of from 1.5 to 3.5 nm.

Example 2. Obtaining bimetallic nanoparticles of platinum-iron (Pt-Fe).

In our experiments we used both the feed pump 9 and 10 devices 1A and 1b filing, as well as the first reactor 2 the second reactor 3. The synthesis of nanoparticles of platinum, which in this experiment was used as a matrix, conducted in the first reactor 2 in accordance with the above-described process. Prepared 6×10-3M solution hexachloroplatinic acid (H2PtCl6×6H2O (Aldrich) in a mixture of methanol with water (at a ratio of methanol:water = 9:1), then added to the polymer PVP (polyvinyl-pyrrolidone, Aldrich) with 10-fold excess of the monomer with respect to the ions of Pt4+. After you have specified the parameters of the reaction (temperature: 150°C, a pressure of 45 bar, flow rate: 1 ml/min), the system was washed with methanol and began the experiment. The first source liquid from the tank 7 by the supply pump 9 was pumped into the reactor 2, where occurred the formation of particles. 6×10-3M solution of ferric chloride (FeCl2, Aldrich) of the supply pump 10, by changing the flow rate, forced to drop the mixer 5, where this solution was mixed with the colloidal solution containing Pt particles formed in the reactor 2. This reaction mixture was admitted into the reaction zone 15 (also heated to 150°C), where iron was connected with platinum. The product was a colloidal solution containing bimetallic particles of Pt-Fe, which are extremely useful for the selective catalytic reactions. Synthesized colloidal solution was collected in a reservoir 21 for the product. After C the tesa product was analyzed by transmission electron microscope (THEMES) as described above.

THE image bimetallic nanoparticles Pt-Fe are shown in figure 3. The particle size is significantly different from sizes in the previous example. The size increased to values of about 10 nm by the addition of another element (iron) to existing blocks Pt.

Conclusions: corresponding to the invention, the device 50 and corresponding to the invention process (method), confirmed the possibility of obtaining bimetallic nanoparticles, which play a critical role in catalysis. By setting the ratio of the flow rates of raw materials and systematically changing them can effectively, quickly and in a wide range to vary the composition and nanostructure of the product.

Example 3. Receipt of semiconductor nanoparticles (CdSe).

The CdSe nanocrystals, forming a colloidal solution was obtained by high-temperature decomposition of the original materials in the system of continuous use of the device 50 corresponding to the present invention. The first stage was prepared initial solution in an argon atmosphere: 47,5 mg (6×10-4M) selenium powder (Se, Aldrich) was dissolved in 10 ml though (TOP, Aldrich). With constant stirring to the solution was added 32 mg (1,4×10-4M) of cadmium acetate (Cd(AcO)2, Aldrich) and 1.5 g (3,9×10-3M) trioctylphosphine (TORO, Aldrich). The resulting mixture was stirred for another 10 min at 40°Statem this original solution from the reservoir 7 to the source of fluid via the feed pump 9 was pumped into the reactor 2. Nanocrystals of CdSe semiconductor type ("quantum dots") received in the second reactor 3, using pre-selected and specified reaction conditions: the reaction temperature was changed in the range from 180°C to 300°C, pressure set value to 100 bar, and the flow rate was changed in the range from 1 to 10 ml/min For the reaction was monitored by means attachable spectroscopic device in continuous mode was measured optical properties of colloidal solution in the flow cell. From well-known properties of the quantum dots" semiconductors, it follows that the wavelength of the absorbed and emitted light is strictly dependent on particle size, and therefore the device 4 for the collection and analysis of the reaction product, equipped with a flow detector, provided continuous information about the synthesized nanoparticles and the parameters that describe them. For changes to the properties of the reaction products caused by systematic changes in the parameters of the reaction, it was possible to accurately track based on the information received from the flow detector.

The results presented in figa and 4b. On figa shows THE image of CdSe crystals, and fig.4b - radiation spectra of colloidal solutions containing CdSe nanocrystals synthesized at different flow velocities.

Analysis of THE images (figa) ol the b product synthesis clearly shows the synthesis of CdSe nanocrystals using device 50 and the corresponding method were selective, and sizes of particles occupy a well-defined, narrow interval (2-3 nm). In addition, the use of flow detector 20 clearly shows that the size of the resulting nanoparticles can be easily and quickly changed by changing the flow rate, as indicated by a significant shift of the wavelength of emitted light.

Conclusions: the CdSe nanoparticles with dimensions that fit in a definite interval of values were successfully synthesized in accordance with the invention device 50 using the proposed in the invention process. Spectroscopic device, which optionally can be attached to the device 50 and which is open in the product flow, proved to be suitable for continuous flow determine the quality of the synthesized product. The optical detector 20, it was shown that increasing the flow rate, you can easily and quickly reduce the size of the particles; using the detector directly produces a feedback signal from the process.

Example 4: Obtaining nanoparticles of 2-(4-isobutylphenyl)-propionic acid

In these experiments, using the device 50 were obtained nanoparticles of 2-(4-isobutylphenyl)-propionic acid. The original process is prepared, after dissolving 3 g of dextran (Aldrich) in an aqueous solution of 1.35 g of sodium salt of 2-(4-isobutylphenyl)-propionic acid (Aldrich) in 100 ml of distilled water at 25°C. Prepared the original solution was applied by a pump device 1A filing in the first reactor 2 with a speed of 3 ml/min in the branch mixer 5 via a second device 1b of the feed was pumped 5×10-3M solution of hydrochloric acid at a rate of 0.5-1.2 ml/min, where it was mixed with a solution containing sodium salt of 2-(4-isobutylphenyl)-propionic acid, and coming from the first reactor 2. The formation of nanoparticles occurred in a continuous manner at atmospheric pressure due to the effect of deposition in the hydrochloric acid solution is injected into the ground mixer 5. The obtained colloidal solution, passing the second reactor 3, reached an inline analyzer dynamic light scattering (DLS, Dynamic Light Scattering) in the device 4, which can continuously determine the size of the resulting nanoparticles. The size of synthesized nanoparticles could widely be controlled by flow rate, pressure and the amount of dextran. Figure 5 presents the results of the particle size and distribution of particle sizes, obtained from light scattering measurements.

The structure of nanoparticles of 2-(4-isobutylphenyl)-propionic acid obtained by the precipitation method h is of Lebanon, investigated x-ray diffraction analysis using a powder diffractometer Philips PW1050/1870 RTG. Measurements showed that the particles are amorphous. A broad reflection band in the range of angles of 15°-20° (double angle - 2θ) indicates the amorphous structure of the dextran. Reflections typical of crystalline 2-(4-isobutylphenyl)-propionic acid, are not detected. X-ray diffraction pattern shown in Fig.6.

Example 5. Obtaining nanoparticles of 1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-5-yl)phenylsulfonyl]-4-methylpiperazine.

In these experiments, using the device corresponding to the present invention were obtained nanoparticles of 1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-5-yl)phenylsulfonyl]-4-methylpiperazine. As starting material used is a solution of 250 mg of citrate 1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-5-yl)phenylsulfonyl]-4-methylpiperazine (SD) in 100 ml of distilled water. The prepared solution was passed through the reactor 2 with a flow rate of 3 ml/min using the device 1a supply. In tee mixer 5 via a second device 1b of the feed was pumped solution of 25 mg of carbopol 980 (Lubrisol) in 100 ml of distilled water at a rate of 1 ml/min, where it was mixed with a solution containing citrate 1[4 ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-5-yl)phenylsulfonyl]-4-methylpiperazine, and coming from the first reactor 2. The formation of nanoparticles occurred in a continuous manner at atmospheric pressure due to the formation of a polyelectrolyte complex solution of carbopol 980, filed in the branch mixer 5. The obtained colloidal solution passed through a second reactor 3, fell in measuring dynamic light scattering in the device 4, which was included in the device 50, and is made with the possibility of continuous measurement of the size of the resulting nanoparticles. Had the ability to control the size of nanoparticles in a wide range by changing the flow rates, pressure and quantity of the added carbopol 980 (see Fig.7).

Example 6. Obtaining nanoparticles cyclohexyl 1-hydroxyethyl carbonate 2-ethoxy-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodithiol-6-carboxylic acid.

In these experiments, with the help of the device 50 corresponding to the present invention, obtained nanoparticles cyclohexyl 1-hydroxyethyl carbonate 2-ethoxy-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodithiol-6-carboxylic acid. As starting material used is a solution of 100 mg of cyclohexyl 1-hydroxyethyl carbonate 2-ethoxy-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodithiol-6-carboxylic acid and 200 mg of polyethylene glycol (PEG 6800, Evonik) in 100 ml of 2-(2-ethoxyethoxy)is canola. The prepared solution was passed through the reactor 2 with a flow rate of 1 ml/min using the device 1A supply. In tee mixer 5 via a second device 1b filing distilled water was pumped at a rate of 1 ml/min, where it was mixed with a solution containing cyclohexyl 1-hydroxyethyl carbonate 2-ethoxy - 1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodithiol-6-carboxylic acid, and coming from the first reactor 2. The formation of nanoparticles occurred in a continuous manner at atmospheric pressure due to the effect of sedimentation in distilled water, supplied to the branch mixer 5. The obtained colloidal solution passed through a second reactor 3, fell in measuring dynamic light scattering in the device 4, which was included in the device 50, and is made with the possibility of continuous measurement of the size of the resulting nanoparticles. Had the ability to control the size of nanoparticles in a wide range by changing the flow rate, pressure and quantity of the added polyethylene glycol (see Fig).

Example 7. Obtaining nanoparticles (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one.

In these experiments, using the device 50 corresponding to the present invention, obtained nanoparticles (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one. As starting material used is a solution of 200 mg (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one and 200 mg polyvinyl pyrrolidone (PVP K-25, Aldrich) in 100 ml of dimethyl sulfoxide. The prepared solution was passed through the reactor 2 with a flow rate of 0.3 ml/min using the device 1A supply. In tee mixer 5 via a second device 1b of the feed was pumped distilled water at a rate of 1.2 ml/min, where it was mixed with a solution containing (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one, and coming from the first reactor 2.

The formation of nanoparticles occurred in a continuous manner at atmospheric pressure due to the effect of sedimentation in distilled water, supplied to the branch mixer 5. The obtained colloidal solution passed through a second reactor 3, fell in measuring dynamic light scattering in the device 4, which was included in the device 50 and is made with the possibility of continuous measurement of the size of the resulting nanoparticles. Had the ability to control the size of nanoparticles in a wide range by changing the flow rates, pressure and amount of the applied polyvinyl-pyrrolidone (see Fig.9).

It should be emphasized that due to the cooling effect of prototechno the heat exchanger, applied in the device corresponding to the present invention, the process of obtaining metal nanoparticles is extremely reproducible. In example 8 was awarded the platinum nanoparticles. In the experiments used two types of heat exchangers 14, 16. In the first case, the heat exchanger had air cooling, while in the second case used the built-in device 50 a counter-current heat exchanger. To investigate the reproducibility of the experiments were repeated five times with the same arguments. Analysis of samples was performed on a transmission electron microscope (Philips CM 20 THEMES).

Example 8. Obtaining nanoparticles of platinum (Pt).

The first stage was prepared with the original solution as follows: prepared 6×10-3M solution hexachloroplatinic acid (H2PtCl6×6H2O (Aldrich) in a mixture of methanol with water (at a ratio of methanol:water = 9:1), then added to the polymer PVP (polyvinyl-pyrrolidone, Aldrich) with 10-fold excess of the monomer with respect to the ions of Pt4+. The role of polymer consisted in preventing the aggregation of Pt nanoparticles to the synthesis turned out to be a stable colloidal solution.

In the second stage by means of the device 22 controls were set to the parameters of the reaction (temperature, pressure, and flow rate). The experiment was performed at a flow rate of 1 ml/min, those which the reaction temperature 150°C (in the reaction zone 13 of the first reactor 2) and a pressure of 45 bar.

Prior to the experimental reaction system was washed with methanol, which was pumped into the reactor 2 by the supply pump 9. After checking that the system does not contain any impurities and reaction zone 13 is stably holds the settings in the reservoir 7 to the source of fluid put the initial solution and turned on the pump supply. When mentioned flow rate of 1 ml/min it took 5 min to the first drops of the synthesized colloidal solution appeared in the tank 21 of the product. Analysis of samples was performed on a transmission electron microscope (Philips CM 20 THEMES). The distribution of nanoparticle size was determined on several hundred particles by counting manually.

The obtained results are shown in figure 10 (table 1). The results show that when using a counterflow heat exchanger, the average size of nanoparticles of platinum (Pt) was about 3.5-4 nm at uniform distribution of particle size, and the specified value is well reproduced in repeated experiments. However, when using air cooling, the size of the resulting nanoparticles ranged from 8 to 15 nm at a low reproducibility.

The particle size of Pt is increased if the cooling efficiency is reduced, i.e. if the cooling of the reaction mixture is slower. Due to the fact that the reaction mixture is cooled slow is it, nanoparticles spend more time in the environment with increased temperature, and therefore, the probability of aggregation centers of crystallization increases, which leads to the formation of larger nanoparticles.

Conclusion: by using the appropriate invention device 50 and connected to the device counterflow heat exchanger was successfully synthesized Pt nanoparticles quite certain size and with a good reproducibility.

1. The device (50) for nanoparticles in continuous mode, containing
the first device (1A) the filing of a first supply pump (9), connected to a source (7) of the source material,
the first reactor (2)containing the first heated reaction zone (13),
the second reactor (3)containing a second heated reaction zone (15), where all these devices connected to the channel of movement of the material sequentially in the specified order,
at least one regulator (18) pressure, is installed in the specified channel movement,
the mixer (5)installed in the specified channel of movement of the material between the first reactor (2) and the second reactor (3),
the second device (1b) the filing with the second feed pump (10), connected to a source (8) of the source material, and the second feed pump (10) is in fluid connection with a mixer (5),
device is on (22) control, made with the ability to control the set pressure specified by the regulator (18) pressure and/or temperature values above the heated reaction zone (13 and 15),
characterized in that after each of the heated reaction zone (13) in the channel of movement of the material has the appropriate cooling device (14, 16) to reduce the size of the nanoparticles in their production process, and the cooling device (14, 16) are additionally made with the possibility of termination of this process for producing nanoparticles.

2. The device according to claim 1, characterized in that the cooling device (14)connected to the first reactor (2), installed in the channel of movement of the material after the first of the heated reaction zone (13).

3. The device according to claim 1, characterized in that it further comprises a device (4) analysis of the final product, which is composed of a dynamic light scattering analyzer, connected to a cooling device (14, 16) for continuous monitoring and measurement of the resulting nanoparticles and the distribution of particle sizes and to adjust the cooling device (14, 16) in accordance with the measured parameters of the nanoparticles, and the device (4) analysis of the final product included in the channel of movement of the material after the last reactor (3).

4. The device according to claim 3, characterized in, Thu the controller (18) pressure is installed in the channel of movement of the material between the last reactor (3) and a device (4) analysis of the final product to maintain the pressure constant along a given channel movement,

5. The device according to claim 1, characterized in that the cooling device (14, 16) are counterflow heat exchangers to control the distribution of the resulting nanoparticles by size.

6. Application device according to any one of claims 1 to 5 for nanoparticles/nano-emulsions/colloidal solutions containing at least one component, preferably a metal, or a biologically active organic molecules.

7. The use according to claim 6, where the resulting nanoparticles have a structure of type "core-shell".

8. The use according to claim 6, where the nanoparticles of biologically active organic molecules are preferably nanoparticles of active pharmaceutical ingredients.



 

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4 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: aqueous solution of quantum dots based on cadmium selenide coated with mercapto acids is stabilised by adding sodium sulphite until achieving its concentration of 0.02-0.2 mol/l in the solution.

EFFECT: high stability of aqueous solution of quantum dots while preserving luminescence brightness, hydrodynamic diameter and active groups of the quantum dots.

2 dwg

FIELD: chemistry.

SUBSTANCE: aqueous solution of quantum dots based on cadmium selenide coated with mercapto acids is stabilised by adding sodium sulphite until achieving its concentration of 0.02-0.2 mol/l in the solution.

EFFECT: high stability of aqueous solution of quantum dots while preserving luminescence brightness, hydrodynamic diameter and active groups of the quantum dots.

2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical microcapsulation of cephalosporins related to β-lactam antibiotics. As a microcapsule shell, the method of pharmaceutical microcapsulation of cephalosporins uses konjac gum; the microcapsules are prepared by physical-chemical technology implying the precipitation in a non-solvent using two precipitants - carbinol and diethyl ester in ratio 1:3; the method is conducted at 25°C with no special equipment.

EFFECT: invention provides simplified and accelerated preparation of the water-soluble pharmaceutical microcapsules of cephalosporins in konjac gum, loss reduction in preparing the microcapsules (higher yield-mass).

3 ex

FIELD: medicine.

SUBSTANCE: claimed invention relates to medicine and describes method of obtaining delivering particles of fragrance, containing core material and envelope, said envelope at least partially surrounds said core material and at least 75% of said delivering particles of fragrance are characterised by tensile strength from approximately 0.2 MPa to approximately 10 MPa, with particle size from approximately 1 micron to approximately 80 micron and thickness of particle walls from approximately 60 nm to approximately 250 nm; and said delivering particles of fragrance are characterised by release of fragrance from 0% to approximately 30%. In addition to creation of possibility to reduce number of agent which produces favourable impact, such particles make it possible to extend spectrum of applied agents which produce favourable impact.

EFFECT: in cases of application in compositions, for instance, detergents, or compositions for fabric care, such particles increase efficiency of delivery of agent which produces favourable impact, making it possible to use reduced amounts of agents which produce favourable impact.

11 cl, 9 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a powder coating composition obtained from aqueous dispersion containing polymer-encapsulated particles, said particles including particles encapsulated in a brittle polymer which can easily break up under ambient conditions. The invention also discloses a method of preparing an aqueous dispersion of particles encapsulated in a brittle polymer, a base which is at least partially coated with a coating deposited from said composition, a multilayer composite coating, a method of preparing a powder coating composition, a method of preparing an aqueous dispersion of particles encapsulated in a brittle polymer and a powder coating composition formed from said dispersion prepared using said method, as well as a reflecting surface which is at least partially coated with a layer which gives the colour of an uncovered coating deposited from disclosed powder coating compositions.

EFFECT: obtaining aqueous dispersion of particles encapsulated in a brittle polymer in which repeated agglomeration of particles is minimised and which enables to obtain a powder coating composition which contains multiple polymer-encapsulated particles having maximum turbidity so that the coating has absorption or reflection in the visible spectrum which is close to that of the given coating.

22 cl, 14 ex, 1 tbl

FIELD: process engineering.

SUBSTANCE: invention relates to production of minor spherical particles of active agent in sole liquid phase solution. Sole liquid phase comprises active agent, agent facilitating phase separation and first thinner. Phase separation is induced at controller rate in solution to cause separation active agent into "fluid-solid" and to form liquid and solid phases. Note here that inducing comprises solution cooling. Solid phase contains minor spherical particles of active agent. Liquid phase comprises agent facilitating phase separation and thinner. Minor spherical particles feature particle size varying from 0.01 mcm to about 200 mcm.

EFFECT: minor spherical particles of active agent in sole liquid phase solution.

77 cl, 49 dwg, 4 tbl, 36 ex

FIELD: process engineering.

SUBSTANCE: invention maybe used for efficient fire extinguishing, fast cooling of overheated structures and production of lower-flammability compounds. Microcapsules have a micro-sphere-like core containing water or water solution in gel state, main shell around said core to provide for core stable shape and composition and rule out water evaporation therefrom the core, and, additionally, comprises outer shell with lyophilic properties. Versions of proposed methods comprises producing aforesaid core via interaction of appropriate initial water solutions to be placed in microsphere and containing appropriate components of the shell with components of solutions to be precipitated and used for producing and cross-linking of gel, and producing additional lyophilic shell via interaction of components of initial solutions with appropriate components in organic medium.

EFFECT: high efficiency in fire extinguishing or fast cooling of overheated structures.

21 cl, 1 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of polymer material, and specificaly to use of particulate polymer material as an active agent carrier. The polymer material is a polymer obtained from copolymerisation of pyrrole with quadratic or croconic acid or its derivative.

EFFECT: use in accordance with the invention enables to use polymer material as a composition in form of particles as an absorbent or prolonged release agent.

16 cl, 8 dwg, 1 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a solid re-dispersible emulsion which is a direct emulsion of fabric softener encapsulated in a polysaccharide shell which is stabilised by ions of polyvalent metals selected from Ca2+, Sr2+, Ba2+, Al3+, Cu2+, Zn2+, where the shell is initially insoluble in water but becomes soluble in water through ion donation. The polysaccharide is biodegradable and is selected from a group comprising alginates and carrageenans. Similar solid re-dispersible emulsions are primarily used in agents for washing or taking care of clothes. Powdered fabric softeners are easy to store, apportion and, if necessary, combine with powdered detergents during production.

EFFECT: invention enables production of fabric softeners previously produced as liquid compositions in solid powdered form.

14 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to capsular additives for rubber, obtained in form of microcapsules with a polymer wall and a nucleus, which contains at least one additive for rubber. The capsule wall is formed by at least one component from a reactive resin and at least one component from a polyelectrolyte or ionomer component. The reactive resin is melamine formaldehyde resin and/or polyurea resin. The invention also relates to a method of preparing such microcapsules. The proposed microcapsules are used for vulcanising natural and synthetic rubber. The microcapsules are thermally and mechanically stable in conditions for preparing and processing rubber compositions in kneading machines, manglers or twin-screw extruders at temperatures ranging from 120°C to 140°C.

EFFECT: microcapsular additives are uniformly distributed in rubber mixture and prevent formation of a heterogeneous rubber/additive system.

30 cl, 12 ex

Microcapsules // 2359662

FIELD: medicine, pharmaceutics.

SUBSTANCE: microcapsules, in which water droplet or droplets including the dissolved active ingredient are incapsulated in the hardened hydrophobic cover-matrix, are described. Also the methods of obtaining of the specified microcapsules and their application are described.

EFFECT: development of microcapsules which possess the improved stability and provide the adjustable and-or prolonged release of an active ingredient.

40 cl, 8 dwg, 4 tbl, 8 ex

FIELD: medicine; pharmacology.

SUBSTANCE: carrying out of treatment of disease, in particular, diabetes, by implantation of the encapsulated devices containing a covering and cells, thus density of cells makes 100000 cells/ml, and the covering contains acrylate polyethylene alcohol (PEG) high density with molecular mass from 900 to 3000 Dalton, and also a sulfonated comonomer.

EFFECT: minimisation of the tissue response, augmentation of concentration of cells and augmentation of time of viability of cells in the specified devices.

83 cl, 33 dwg, 8 tbl, 20 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical microcapsulation of cephalosporins related to β-lactam antibiotics. As a microcapsule shell, the method of pharmaceutical microcapsulation of cephalosporins uses konjac gum; the microcapsules are prepared by physical-chemical technology implying the precipitation in a non-solvent using two precipitants - carbinol and diethyl ester in ratio 1:3; the method is conducted at 25°C with no special equipment.

EFFECT: invention provides simplified and accelerated preparation of the water-soluble pharmaceutical microcapsules of cephalosporins in konjac gum, loss reduction in preparing the microcapsules (higher yield-mass).

3 ex

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