EA041207B1 - METHOD FOR PRODUCING METHYLSILICON ACID HYDROGEL WITH PROPERTIES OF SUPRAMOLECULAR STRUCTURES AND HYDROGEL PRODUCED BY THIS METHOD - Google Patents

Description

The invention relates to the field of chemistry, in particular to the synthesis of chemical compounds - polymethylsiloxanes (methylsilicic acid hydrogels), and can be used in medicine and veterinary medicine as a sorbent that has selective properties.

Polymethylsesquioxanes of the general chemical formula are known:

[CH3SiO1,5] describing a number of substances, including methylsilicic acid hydrogel, which is represented by the general formula:

(CH3SiO1.5-nH2O)", where n=30-46.

These compounds are network polymers of complex topology surrounded by a hydrated shell. The main way to obtain them is to carry out polycondensation from the alkaline phase.

Based on the structural representation of these polymers, it should be taken into account that they contain residual uncondensed hydroxogroups (OH groups) and the generalized empirical formula of the polymer in linear form (excluding the hydration shell) has the form:

(CH3Si)nO(n.1)OH(n ₊ 2) as the polycondensation proceeds, the polymer branching occurs with the formation of an intermediate structure of the form:

(CH381)po(n-1+k)OH(n+2-2k) (1) where osk _s 2.( _n +l+l.(-iy).

Obviously, at k=0, the polymer is a form with a predominantly linear topology. The existence of the polymer in this form is more inherent in alkaline solutions;

when the polymer is a form with a cyclic topology, completely condensed, without the content of OH groups. This form of polymer is inherent in methylsilicic acid xerogels; when o < k < 1. ( _n + 1 + 1. (-y) the polymer is a form with an intermediate between linear and cyclic topology. Actually, this form is inherent in a group of compounds under the general name methylsilicic acid hydrogel.

Polycondensation of OH groups with a limiting linear structure (k = 0) is described by a chemical equation of the form (CH3Si)nO(n.1)OH(n ₊ 2)^(CH3Si)nO(n.1 ₊ k)OH(n ₊ 2.2k) + kH2O

The above reaction is a process of intramolecular polycondensation and is accompanied by cyclization of the molecule.

Growth of a polymer chain by the example of _{polycondensation} ^interaction of two molecules with a structure 0<<7<r (m + ; + r(-l) ^m )) ____ within intermediate topologies (m<n and 222 222 is expressed as a chemical equation:

(CH3Si)nO(n-l+k)OH(n+2-2k) + (CH3Si)mO(m-l+q)OH(in+2-2q) —► —► (CH3Si)(n+m )O(m+n-2+k+q+p)OH(n+m+4-2k-2q-2p) + pHgO, where

ISp sl-(m + 2-2 _g >

A known method for producing a hydrogel of methylsilicic acid, which includes preparing a working mixture of methyltriethoxysilane and an organic solvent, preparing a hydrolytic mixture with hydrochloric acid and purified water, making an alkaline solution, hydrolysis of methyltriethoxysilane in the presence of an acid catalyst, followed by alkaline treatment, exposure of the reaction mass, grinding the resulting alcogel methylsilicic acid, its subsequent washing with purified water to form a methylsilicic acid hydrogel. In the preparation of the working mixture, an aqueous solution of ethanol with a volume fraction of ethyl alcohol from 60 to 96.5% is used as an organic solvent, and the quantitative volume ratio of methyltriethoxysilane and an organic solvent in the form of an aqueous solution of ethanol is (1-1.2): (2-2 ,7), respectively, while methyltriethoxysilane is used with a mass fraction of the main substance of at least 98%, and the hydrolysis of methyltriethoxysilane is carried out at a volume ratio of the working mixture and hydrolytic mixture (3-3.5): (0.7-1.5), respectively, at the same time, the time for introducing the hydrolytic mixture into the reaction mass is 30-40 minutes, and the exposure of the resulting reaction mass is carried out for 3-3.5 hours at a pH value of at least 3, and after the completion of the hydrolysis of methyltriethoxysilane, an alkaline solution is introduced into the resulting reaction mass, which has a temperature of 16-30°C, after which the resulting

- 1 041207 methyl silicic acid alcohydrogel is kept for maturation for at least 7.5 hours, while the methyl silicic acid alcohydrogel ripening process is carried out until a colorless intermediate with slight opalescence is obtained, and the crushed methyl silicic acid alcohydrogel is washed by introducing into it water purified at a rate 2-4 liters per hour [UA No.

90988, C08G 77/00.2010].

The known method has the following disadvantages.

For the complete elimination of etoxygroup, the necessary condition is the presence of a strongly alkaline medium (for the complete saponification reaction, the alkali concentration must be at least 5 mol/l) and an elevated temperature of the reaction mixture (at least 60°C). The use of acids at the stage of polycondensation for alcohol solutions leads to the formation of a by-product of diethyl ether. Since the product has adsorption properties, it adsorbs both reaction products and ethyl alcohol from the solvent medium. The final product obtained by this method contains impurities: ethyl alcohol, diethyl ether and unsaponified ethoxysilane. The removal of these impurities from the product requires a large amount of purified water and cannot be carried out completely in accordance with the conditions given in the method of obtaining.

A known method for producing a sorbent based on a methylsilicic acid hydrogel of the general formula {(CH ₃ SiO1, ₅ )-mH ₂ O}n, where m is the number of water molecules in the link {(CH ₃ SiO1, ₅ )-mH ₂ O}, n - the number of {(CH ₃ SiO1, ₅ )-mH ₂ O} units in the hydrogel, in which a hydrogel is obtained from the starting material in the presence of a strong acid in an alcohol medium by hydrolysis followed by polycondensation in an alkaline medium, which is kept and crushed, and the resulting product is washed to a neutral reaction, while a strong acid is used at a concentration of 0.5 to 1.2%, and an alkaline reagent for the implementation of the polycondensation reaction is used at a concentration of 20 to 27% [UA No. 72402, C08G 77/04, 2012].

Just as in the previous case, the use of acids at the stage of polycondensation for alcohol solutions leads to the formation of a by-product - diethyl ether. Since the product has adsorption properties, it adsorbs both reaction products and ethyl alcohol from the solvent medium. The final product obtained by this method contains impurities: ethyl alcohol and diethyl ether. The removal of these impurities from the product also requires a large amount of purified water and cannot be carried out completely in accordance with the conditions given in the production method.

A known method for producing a hydrogel of methylsilicic acid, according to which the process of polycondensation of a solution of sodium (or potassium) methylsiliconate with a concentration of 1.75 to 2.30 mol/l is carried out by adding a solution of a strong acid to it until a hydrogel is formed, which, after exposure for 30-90 min (ripening) is crushed and then activated by the action of a dilute solution of a strong acid with a concentration of 0.04 to 0.15 g-eq/l, followed by washing with water until a neutral reaction [RU No. 94008432 A1, C08G 77/02. 1995].

The formed gel is treated with dilute solutions of strong acids (activation stage), which leads to the final condensation of hydroxogroups and, thereby, leads to the loss of the properties of supramolecular structures and the loss of conformational mobility.

Closest to the claimed invention is a method for producing a sorbent based on methylsilicic acid hydrogel of the general formula: {(CH ₃ SiO1, ₅ )-nH ₂ O} ", including adding a strong acid solution to a solution of sodium or potassium methylsiliconate until a product is formed, followed by holding, grinding , activation of the product by adding a dilute solution of a strong acid and washing the product to a neutral reaction, while using a solution of sodium or potassium methylsiliconate at a concentration of 2.35-2.95 mol / li, varying the values of the coefficient n up to 495, various final forms of the sorbent are obtained with selective sorption properties of relatively macromolecular substances with a molecular weight of 10,000-500,000 D and more [UA No. 82774, C08G 77/00.2008].

This method has the following disadvantages.

Since one of the components of the mixture is a strong acid, and the other is an alkaline solution of sodium methyl siliconate, a salt of a strong alkali and a strong acid is formed, which does not have a protective effect on OH groups (solutions of such salts have an acidity close to neutral). In this case, the transformations in the system entirely depend on the ratio of the alkaline component, which decreases as the synthesis proceeds, and the strongly acidic component.

Carrying out the reaction under the above conditions makes it impossible to control its course and leads to a product that is heterogeneous in physical and chemical parameters, which makes it difficult to standardize.

The use of dilute solutions of strong acids at the stages of obtaining the product leads to the formation of low molecular weight fractions of the product, which contribute to a decrease in the adsorption capacity, which is positioned for it as the main characteristic. According to the requirements of good pharmaceutical manufacturing practices, the formation of low molecular weight fractions should be considered as concomitant impurities from the standpoint of the integrity of the composition of the active pharmaceutical ingredient, which is methylsilicic acid hydrogel.

On the scale of industrial production, wastewater is formed that contains dissolved and suspended substances at levels of multiple excess of maximum permissible concentrations, which requires the creation of separate treatment complexes and creates problems for further disposal.

Known hydrogel methylsilicic acid with high sorption capacity and selectivity for medium molecular weight toxic metabolites (enterogel-super) formula:

{(CH3SiO1,5)-nH2O}«, where n = 44-49, characterized by sorption capacity according to Congo red 3.3-4.6 mg/g [RU No. 94008432 A1, C08G 77/02.1995].

Such a hydrogel has purely sorption properties with low selectivity.

Closest to the claimed hydrogel is a hydrogel of methylsilicic acid as a sorbent of medium molecular weight metabolites of the formula {(CH ₃ SiO _{1; 5} )-nH ₂ O} _TO , where n = 44-49, which are characterized by a sorption capacity according to Congo red 3.3-4, 6 mg/g [RU No. 2111979 C1, C08G 77/02.1998].

The specified hydrogel, like the previous analogue, has a purely sorption properties with low selectivity, heterogeneous in physical and chemical parameters, which makes it difficult to standardize. In addition, the use of dilute solutions of strong acids leads to the formation of low-molecular fractions of the product (associated impurities), which help to reduce the adsorption capacity, which is positioned for it as the main characteristic.

The invention is based on the task of creating a method for producing methylsilicic acid hydrogel with the properties of supramolecular structures, which was high-tech, cost-effective and environmentally friendly.

The second task set as the basis of the invention is to obtain a hydrogel, which should have developed selective adsorption properties and, additionally, the properties of supramolecular structures in order to be able to use it in medicine and veterinary medicine as an individual substance with therapeutic properties, as well as a matrix for complex compositions. with the functions of controlled and/or prolonged release and/or targeted delivery of the substance.

The problem is solved by the fact that in the method of obtaining a hydrogel of methylsilicic acid with the properties of supramolecular structures, in which a solution of sodium methylsiliconate is used, according to the invention, a gaseous acidic agent is passed through the solution of sodium methylsiliconate loaded into the reactor for bubbling, the resulting product is floated in the neck of the reactor, after the end of the process, the product is unloaded from the reactor, evacuated to remove residual gas and washed with water purified to pH-6.5-7.0 without residual anions, obtaining a methylsilicic acid hydrogel with the properties of supramolecular structures, which is described by the formula:

[{CH3Si(OH)2Oo.5}a/n{CH3Si(OH)O}b/n{CH3SiO1.5}c/n] xH2O, where < x < 35; 0 < - < 0.38; 0.19 < - < 0.9; 0.11 < - < 0.49. p ' ’ p ’ ' p

The sparging time is 45 minutes, the sparging rate is 333 ml of the gaseous agent per minute.

As a gaseous acidic agent, carbon dioxide can be used, which is fed through the bottom valve of the reactor, carrying out the process in a closed system.

As a gaseous acidic agent, carbon dioxide can be used, which is fed through the top valve of the reactor, carrying out the process in an open system.

As a gaseous acidic agent, sulfur oxide (IV) - SO ₂ can be used

As a gaseous acidic agent, hydrogen sulfide - H ₂ S can be used.

As a gaseous acidic agent, sulfur oxide (VI) - SO3 can be used

As a gaseous acidic agent, hydrogen chloride - HCl can be used.

The sodium methylsiliconate solution can be dropped dropwise through a comb over the hydrophobic surface of the trough placed in the gaseous acidic agent for 20 minutes.

The second task is solved by obtaining the method according to claim 1 of a methylsilicic acid hydrogel with the properties of supramolecular structures, which is described by the formula: [{CH3Si(OH)2Oo,5}a/n{CH3Si(OH)O}b/n{CH3SiO _t 5} c/n] xH2O, where

I < x < 35; 0 < - < 0.38; 0.19 < - < 0.9; 0.11 < - < 0.49. p p p

Compared with the prototype method of the claimed is manageable, high-tech, environmentally friendly, cost-effective.

The resulting methylsilicic acid hydrogel has developed selective adsorption properties and, additionally, the properties of supramolecular structures, which makes it possible to use it in medicine and veterinary medicine as an individual substance with therapeutic properties, as well as a matrix for complex compositions with the functions of controlled and/or prolonged release and/or targeted delivery of the substance.

A solution of a salt formed by the reaction of a weak acid and a strong base

- 3 041207 performs the protective function of non-condensed hydroxogroups, since the acidity of solutions of such salts is alkaline. The polymer is characterized as mobile conformationally rearranged.

The reaction proceeds in a three-phase system: initial liquid, temporary gas and solid that is formed. Branching of the polymer in the gas phase is not hampered by the counteraction of the forces of viscosity of the liquid medium. The final polymer is obtained with a smaller grid cell size, which determines the severity of selective properties.

The formed gel is not treated with acidic solutions, which does not cause the final condensation of hydroxogroups and allows the formation of the properties of supramolecular structures and determines the conformational mobility. The resulting product has sorption properties with high selectivity and has the properties of supramolecular structures.

On the scale of the industrial implementation of the claimed method, the formed salt solutions in wastewater (for example, sodium carbonate) do not require the creation of an additional complex for the disposal of waste and their further use or disposal, which makes the process cost-effective and environmentally friendly.

The study of the features of the formation of network polymers of the siloxane group led to the creation of a chemical formula that simultaneously describes the topological component of substances along with the chemical composition.

The formation of a network structure in the example of polymethylsiloxanes is due to the presence of three main fragments in the polymer composition (Table 1).

Table 1

Fragment Structure Brute formula, name Description Μ (mono) CH ₃ 1 HO-Si-O1 he {CH ₃ Si(OH) ₂ Oo^} (methyldihydroxosylhemioxyl) Terminal fragments of a molecule with one active site of polymerization, which terminate the growth of the polymer chain. D (BEFORE-) CH ₃ 1 -O -Si -O - 1 he {CH ₃ Si(OH)O} (methylhydroxysiloxyl) Fragments with two active sites of polymerization. The elastic component of the polymer skeleton is formed. Promote internal cyclization of the molecule. T (tri-) CH3 1 -O-Si-O1 o- {CH ₃ SiO^} (methylsilsesquioxyl) Fragments with three active sites of polymerization. Promote trimerization and cyclization of the molecule.

A generalization of the above is the invented chemical formula _of the form:

This formula already describes the topology of the polymer molecule in terms of the quantitative measure of the coefficients a, b, c

The relationship of formulas (1) and (2):

n=a+b+c k=0.5(c-a)+1

Also, formula (2) can be written as the gross form of formula (1) of the form:

(CH381) (n + b + c) O (0 ^ a + b + 1.5 c) OH (2b + b)

Chemical formula (2) describes all possible structures of polymethylsiloxanes. It should be noted that from the standpoint of the features of the formation and properties of the siloxane bond unacceptable [siloxane bond. Voronkov M.G., Mileshkevich V.P., Yuzhelevsky Yu.A. Novosibirsk, Nauka, 1976, 413 s] are structures and fragments of the form:

about sn / . ³ H ₃ C-Si-O-Si-CH ₃ JOI J. _Λ \ / H ₃ C-Si<>Si-CH ₃ H ₃ C-S1< |

-Si \u003d O o O - O

Due to the complexity of the experimental determination of the molecular weights of network polymers, it was proposed to use the chemical formula (2) in the reduced form, namely:

{CH381(OH) ₂ Oo4^{Sch81(OH)0}m,{CH38^ (3)

- 4 041207

Chemical formula (3) is a generalization of chemical formulas (1) and (2). It is convenient to write this formula using the ones indicated in the table. 1 fragment codes. Then the compound can be represented by a formula of the form:

MaDhTc (4) or in the above form:

ml/»1)l/lts/i (5)

In table. Figure 2 shows the main transformations of molecules of formula (4) in the process of polycondensation using the example of molecules with the formulas MaDbTc and M _x D _y Tz.

Table 2. Main transformations of molecules during polycondensation

Type of polycondensation Type Description Reaction course Intermolecular M-M Interact mono-linked fragments containing two OH groups MaDbTc + MxDyT _z ~► M(a+x-2)D(b+y+2)T(c+z) + Н2О Intramolecular M-M MaDbTc-* M(a-2)D(b+2)T(c) + H2O Intermolecular M-D Interact mono-linked fragments containing two OH groups and one OH group, respectively MaDbTc + MxDyTz -* M(a^x-l)D(b^y)T(c^l) + H2O Intramolecular M-D MaDbTc-* M(a-l)D(b+2)T(c+l) + H2O Intermolecular D-D Doubly bonded fragments interact, one OH group each MaDbTc + MxDyTz —► M(a+x)D(b-ty-2)T(c+z+2) + H2O Intramolecular D-D MaDbTc-* M(a)D(b-2)T(c+2) + H2O

A formula for describing the structures of network polymers of polyorganosiloxane of the previously known type [RSiO1,5] has been invented and has the form:

{RiSi(OR2)iOo,5M RiSi(O Ri)OM RiSiOi^Jc , where R1 = CH ₃ , C ₂ H ₅ , CH ₂ =CH the like;

R ₂ =H, CH ₃ , C ₂ H ₅ and others.

Modeling of molecules and calculations of the parameters of molecules with a chain size of up to 50 units in various conformations was carried out in the HyperChem 8.09 software package using the AM1 semi-empirical quantum-chemical method (extended Hückel method), based on the theory of interaction of a system of charged particles. The next optimization of this system was carried out by minimizing the energy and its gradient (rate of energy change) according to the Polak-Ribière algorithm.

Intermolecular and intramolecular interactions were modeled using the examples of systems containing a hydrate environment and/or starting reagents (time zero to interaction) and/or reaction intermediates and/or polycondensation reaction products.

Estimation of the geometric parameters of the target molecules and modeling of the process of polycondensation based on the developed theories of the probabilistic characteristics of the interactions of Flory, Frisch and Stepto [P. Flory, Principles of Polymer Chemistry, Cornell University Press, Ithaca, N.Y., 1953] was carried out by creating macros in Microsoft Excel with subsequent visualization of the topology of the resulting systems based on the randomization of transformations according to Table. 2.

The processing of the geometric characteristics of molecules was carried out by comparing the differences in the normalized coordinates of silicon atoms in model molecules in the presence of a hydrate environment and without it. The visualization of the data obtained was carried out by finding a point equidistant from the geometric coordinates of the atoms of the molecule model. Subsequently, based on the set of distances from the equidistant point to the atoms of the molecule, the topology of the molecule was constructed in polar coordinates.

In FIG. Figure 1 shows an example of a topogram of molecules with an equal number of units: fully cyclic (M ₀ D ₀ T _c/n ), initial linear form (M _2/n D _b/n T ₀ ), and linear form with a hydrate shell (M2/nDb/nTo 45H2O).

As can be seen from FIG. 1, the presence of OH groups significantly affects the conformation of the molecule, while the presence of a hydrate shell does not significantly affect the change in the conformation of the molecule.

The general conclusion of the presented data is the fact that the OH groups of a molecule determine the conformational mobility of the molecule, and a change in certain conditions that provoke both intramolecular and intermolecular polycondensation of OH groups leads to

- 5 041207 manifestation or absence of supramolecular properties of the substance as a whole.

The behavior of a model molecule with a hydrated environment, with a different number of water molecules in the cavities and outside the cavities of the structures, prompted the positioning of the behavior of a substance (methylsilicic acid hydrogel) in the role of supramolecular or supramolecular structures of the host type relative to substances present in the space between the molecules of the guest type. Additionally, systems containing various chemical nature guests were simulated.

Practical confirmation of models and theory was carried out using the developed research methods and instrumental methods of thermogravimetry, cryoscopy, amperometric titration, water titration by the method of K. Fischer, IR, UV-VIS spectroscopy.

The studies were carried out both on samples of methylsilicic acid hydrogel obtained by the method of the prototype and on samples of substances obtained by the claimed method.

The study of the properties of the obtained substances according to the claimed method led to the discovery of unexpected effects, previously unknown and confirmed the hypothesis described above. This makes it possible to position the obtained substances in addition to substances with adsorption properties as substances with a supramolecular structure having host-guest properties as a preorganized conformationally mobile host [Supramolecular chemistry. Per. from English: in 2 volumes / Jonathan V. Shame, Jerry L. Atwood. - M.: ICC Akademkniga, 2007].

The condition for the preorganization of the structure of a substance obtained by the claimed method is the rigidity of its framework. In this case, the substance is positioned as a host tuned to a particular guest and determines the selectivity of the host.

The rigidity of the framework is ensured by the presence in the molecule of the maximum number of T-fragments, based on the data presented in Table. 1 and formulas (4) and (5).

On the other hand, the conformational mobility of the molecule is ensured by the maximum content of OH groups. The elasticity and mobility of the molecule is provided by D-fragments.

To comply with the condition of a conformationally mobile preorganized structure, it is necessary that the values of the coefficients b/n and c/n in the formulas of substances (3) and (5) be maximum.

Theoretically, the given conditions correspond to substances of chemical formulas (3) and (5) with coefficients whose values correspond to the condition

0.10 < < 0.30.

In this case, the ranges of variation of the coefficients of the chemical formula (5) will be < - < 0.38; 0.16 < - < 0.90; 0.11 < - < 0.60.

The calculated content of the OH groups of the compound will be from 16 to 24%.

In practice, the framework rigidity (preorganization) and its maximum conformational mobility can be achieved in practice by protecting the OH groups of the forming polymer and/or by using a phase transition in the molecule formation medium.

In the prototype, the stage of chain termination is used in the synthesis by the influence of weak solutions of strong acids, which does not lead to the protection of OH groups, but rather provokes their polycondensation to the equilibrium stage. As a result, this leads to the formation of a rigid preorganized structure that does not have host-guest properties, but has selectivity only due to the adsorption capacity of the created pores.

The study of the initial solutions of sodium methylsiliconate to determine the molecular weights of dissolved polymers by cryoscopy of the initial and diluted solutions led to the conclusion that the solution contains a set of fragments with 4 to 8 dimensional units. The performed simulation of the mechanics of molecules confirms their overwhelming linear structure. Also, the reason for the linearity of the molecules is the fact that the polymer solution is in a strongly alkaline medium and is saturated with OH groups of the solvent alkali.

Based on the studies, the gelation time of hydrogels obtained by the prototype method using a strong acid solution of various volumes, by pouring up to a fixed volume of sodium methylsiliconate, has an exponential dependence on the molar ratio of the components. This indicates the course of the gel formation reaction according to the radical chain type, since gel formation also occurs in the presence of small amounts of a strong acid. The stages of gelation are proposed to be described as follows:

1. Neutralization of alkali to an equilibrium concentration;

2. Increasing the length of the polymer due to intermolecular interaction (intermolecular polycondensation) of polymers under the action of H ⁺ - ions;

3. Cyclization and trimerization of the polymer (conformational before the organization of the skeleton);

4. Open circuit;

5. In the presence of a sufficient amount of H ⁺ -ions - internal molecular polycondensation (loss of conformational mobility of the molecule due to an increase in the rigidity of the skeleton). The onset of microsyneresis.

To maintain the optimal conformational mobility of the molecule, the necessary condition

- 6 041207 is the introduction of the stage of protection of the OH groups of the molecule.

Due to the fact that in the production method described in the prototype, one of the components of the mixture is a strong acid, and the other is an alkaline solution of sodium methyl siliconate, a salt of a strong alkali and a strong acid is formed, which does not produce a protective effect on OH groups (solutions of such salts are close to neutral in acidity). In this case, transformations in the system entirely depend on the ratio of the alkaline component, which decreases as the synthesis proceeds, and the strongly acidic component.

This disadvantage was avoided in the claimed method. It is known that a solution of sodium methylsiliconate contains an alkali metal cation; therefore, to obtain a weak salt that could contribute to the protective effect on the OH groups of the molecule, it is necessary to use either acids with weak anions or gaseous acid anhydrides.

Among the large number of substances that meet the conditions described above, the authors settled on the use of gaseous acidic agents such as carbon dioxide - CO2;

sulfur oxide (IV) - SO2;

sulfur oxide (VI) - SO3;

hydrogen sulfide - H2S;

hydrogen chloride - HCl.

The methylsilicic acid hydrogels prepared in the following examples have been subjected to a series of studies and surprisingly have the properties of supramolecular compounds.

An analysis of the data obtained leads to the conclusion that the prerequisite for obtaining supramolecular structures is the presence of a protective component for OH groups in the system, and the resulting sodium carbonate solution has a protective effect (in the case of synthesis using carbon dioxide); sodium sulfite (in the case of synthesis using sulfur oxide (IV); sodium sulfide (in the case of synthesis using hydrogen sulfide);

the presence of a gas-liquid phase transition. At the same time, due to the presence of the gas phase, the cyclization and trimerization of the molecule proceeds more easily, in contrast to the same process in the liquid phase (the resistance is exerted by the viscosity of the liquid, which is an order of magnitude greater than that of gases).

Due to the use of gaseous weak acids and anhydrides of weak acids in the gaseous state in the synthesis of hydrogels, both prerequisites are fulfilled, which made it possible to obtain samples with pronounced supramolecular properties. When using sulfur oxide (VI) and hydrogen chloride, only the second prerequisite is fulfilled and the supramolecularity of the samples is less pronounced.

Examples of obtaining methylsilicic acid hydrogel with supramolecular properties:

Example 1 Preparation of a methylsilicic acid hydrogel with supramolecular properties.

Through 200 ml of a solution of sodium methyl siliconate (CNaOH=3.2M; W(n _MC )=180 g/l), carbon dioxide was passed through with a total volume of 15 l. Bubbling time - 45 min. Bubbling speed 333 mlCO ₂ /min. The method of supply is through the bottom valve of the reactor. The process was carried out in a closed system. The resulting product floated in the neck of the reactor. After the end of the process, the product was unloaded from the reactor, evacuated to remove residual gas and washed with water purified to pH 6.57.0 and the absence of residual anions. Product yield 219 g (67% polymethylsiloxane content in sodium methylsiliconate).

Further in the text, the code of the sample according to the example is GGMCC CO2 1

Example 2

The ratio of the initial components as in example 1. The method of supply - through the top valve of the reactor. The process was carried out in an open system. The resulting product floated in the neck of the reactor. Further steps as in example 1. Product yield 232 g (71% based on the content of polymethylsiloxane in sodium methylsiliconate).

Further in the text, the sample code according to the example is GGMKK CO ₂ 2

Example 3

A 20-liter cubic container was filled ¾ with carbon dioxide. An elastic fluoroplastic chute with sides, closed in a ring, equipped with transverse grooves located at an angle of 45° in the horizontal plane to the main main chute was previously placed in the container. The design is put on two shafts, forming an endless conveyor belt. One of the shafts was connected through a gearbox to an electric motor. The angle of inclination to the container was 1530°. The linear speed of movement of the chute from bottom to top was from 30 to 60 cm/min. The supply of a solution of methyl siliconate was carried out drop by drop through a comb with 6 nozzles. The total volume of sodium methyl siliconate is 200 ml. The process time is 20 minutes. Sliding drops of sodium methylsiliconate over the hydrophobic surface of the trough in a CO2 atmosphere under the action of gravity leads to mixing of the drop and to its further solidification. Due to the counteraction of the linear velocity of the chute, the process takes place under conditions as close as possible to the free fall of a drop in the atmosphere of CO ₂ . Further work with the product as in example 1. Product yield 238 g (73% based on the content of polymethylsiloxane in sodium methylsiliconate).

Further in the text, the code of the sample according to the example is GGMKK CO2 3

Example 4-6. Used equipment and processes as described in examples 1-3 with the difference that sulfur oxide (IV) -SO2 was used as gas

Product yields were: 228 g (71%); 222 g (68%); 231 g (70%) respectively.

Further in the text, the sample codes for examples are GGMCC SO2 4, GGMCC SO2 5, GGMCC SO2 6, respectively.

Example 7-9. Used equipment and processes as described in examples 1-3 with the difference that hydrogen sulfide - H2S was used as the gas

Product yields were: 230 g (67%); 228 g (70%); 220 g (66%) respectively.

Further in the text, the codes of the samples according to the examples are GGMKK H2S 7, GGMKK H2S 8, GGMKK H2S 9, respectively.

Example 10-12. Used equipment and processes as described in examples 1-3 with the difference that sulfur oxide (VI) - SO3 was used as the gas

Product yields were: 242 g (69%); 230 g (68%); 245 g (71%) respectively.

Further in the text, the codes of the samples according to the examples are GGMKK SO3 10, GGMKK SO3 11, GGMKK SO3 12, respectively.

Example 13-15. Used equipment and processes as described in examples 1-3 with the difference that gaseous hydrogen chloride - HCl was used as the gas

Product yields were: 234 g (72%); 236 g (72%); 237 g (68%) respectively.

Further in the text, the codes of the samples according to the examples are GGMCC HCl 13, GGMCC HCl 14, GGMCC HCl15, respectively.

experimental part

Hydrogels of methylsilicic acid obtained with known methods [UA No. 82774, C08G 77/00, 2008] (sample code GTMKK 0) and obtained by the method in examples 1-15 were subject to research on the subject of:

adsorption activity;

structure type;

the presence of host-guest properties inherent in supramolecular structures.

The adsorption activity of the samples was studied using the methods described in [AND to RP No. UA/2341/01/01 Methylsilicic acid hydrogel, gel (substance) for the production of non-sterile dosage forms. Applicant CJSC Environmental Protection Company KREOMA-PHARM, Kyiv, 2004, p. 10].

As the adsorbate used: aqueous solutions of indicators of methyl orange (MO), Congo red (KK), Bengal rose (BR) and protein - bovine serum albumin V (BSA). For the BSA solution, UV-Vis spectrophotometry was performed for the biuret complex after treating an aliquot of the protein solution with the biuret reagent. When applying the above methodology for monitoring adsorption activity in relation to the samples obtained in examples 1-9, the indicators reached high values. Considering that manufacturers validate the reliability of the data obtained beyond the nominal value of no more than 140% [State Pharmacopoeia of Ukraine / State Enterprise Scientific Expert Center Pharmacopoeia Center. - 1st ed. - Supplement 2. - Kharkov: State Enterprise Scientific and Expert Center Pharmacopoeial Center, 2008, p. 620], then the working capacity of the technique with reliable values is 4.50 µmol/h. In the case of obtaining overestimated data, the authors of the patent took the indicators of adsorption activity in units of µmol/g as an indicator of the form: more than 4.50 µmol/g. In parallel, the values of the adsorption activity index were calculated using the units of mg/g. The obtained data of indicators of adsorption activity are given in table. 3.

The structure types of the samples were studied using IR spectrometry and a mixed method for the determination of water.

To perform IR spectrometry, samples were preliminarily weighed into vaseline oil and dispersed until a homogeneous suspension was formed.

The resulting mixture was placed in heating cabinets, heated to 150°C, and kept at this temperature for 1:00 to completely remove water from the hydrogel. After the mixture cooled down, it was redispersed. For all prepared samples, the IR spectrum was recorded on an IR Fourier spectrometer of the IRAffinity-1S type. In parallel, the IR spectrum of pure vaseline oil was recorded for further subtraction from the main spectrum.

The described sample preparation technique makes it possible to study the direct structure of the test sample with minimal loss of primary characteristics, which are lost during conventional heating of samples due to the polycondensation of OH groups during heating.

The obtained IR spectra were processed using Fourier transforms of the spectra with an emphasis on the range of wave numbers in the ranges of 1200-1000 cm ^-1 (Si-O-Si - bond) and 800-650 cm ^-1 (Skeletal vibrations of the molecule). In cases where the vast majority of T-fragments are present in molecules, both an increase in the intensity of absorption lines in the range of 800-650 cm ^-1 and a shift in the position

- 8 041207 lines within range. To establish the dependence of the intensity on the concentration of T fragments, the samples were additionally treated with solutions of hydrochloric acid of various concentrations, provoking the polycondensation of the hydrogel and the formation of T fragments according to the schemes given in Table. 2. The starting point for the intensity index in the IR spectrum was its value for completely dehydrated samples (formula M ₀ D ₀ Ti).

To calculate the content of OH groups in molecules, a mixed method for determining water was used: thermogravimetry and water titration according to the K. Fischer method. The thermogravimetric method for determining water was used based on the generally accepted methods for conducting such control. The results of determining the total amount of water were the starting points for further calculation of the composition of the samples.

Titration of water according to the method of K. Fischer was carried out on prepared samples. Sample preparation consisted of pre-mixing methylsilicic acid hydrogel with various amounts of methyl alcohol with a known water content. Mixing was carried out using the gravimetric method. Due to the fact that, when mixed with a hydrogel, methyl alcohol initially dissolves in the water of the hydration shell and partially provokes solvate substitution and polycondensation of OH groups, the use of various ratios of methyl alcohol and hydrogel in extrapolation to zero methyl alcohol content makes it possible to calculate the content of OH groups in the sample. The final value of the content of OH groups in the samples was carried out by subtracting from the mass of water obtained by the thermogravimetric method, the mass of water obtained by extrapolation to the zero content of methyl alcohol when titrating water according to the K. Fischer method, followed by multiplying the result by two. The calculation results are given in Table. 3.

In the course of the studies, hydrogels obtained using known methods [UA No. 82774] are mainly described by formulas with ranges of coefficients

0.05 <- < 0.24; 0.07 <-< 0.18; 0.63 < - < 0.85, η η η have the ratio of D- and T-fragments from 0.06 to 0.11 and the content of OH groups from 12 to 26%. Hydrogels obtained by the method are described by formulas with coefficient ranges < - < 0.38; 0.19 < - < 0.9; η'n

0.11 < - < 0.49, n have the ratio of D- and T-fragments from 0.10 to 0.15 and the content of OH groups from 20 to 24%.

Based on the studies carried out, the general chemical formula of methylsilicic acid hydrogels obtained according to examples 1-15 has the form

[{CH381(OH)gOo,5MSN381(OH)0}^^ xH ₂ O or in abbreviated form:

Ma/nDb/nTc/n * xH1O, where < x < 35;

O < - < 0.38; η

0.19 < - < 0.9; η

0.11 < - < 0.49

Table 3 Main properties of the studied compounds and their chemical formulas

No. example a Sample Code Name of the adsorbate Name of the adsorbate Dry residue, % Content of OH groups, % Compound formula MO CZK BR BSA MO | 1 hr j 1 BR 1 BSA Molecular weight of the adsorbate 327.3| 696.7| 1017.7| 69000 Adsorption activity, µmol/g Adsorption activity, mg/g GGMCCO 3.94 3.42 2.13 0.072 1.290 2.383 2.168 4.968 9.63 20.29 Mo,isDo,i7To,68 23H ₂ O ___________1 GGMCC SO ₂ 1 4.50* 4.50* 4.50* 0.219 3.928 7.872 9.077 15.111 11.39 23.96 Mo.iDo.7sTo,p 20H ₂ O 2 GGMCC SO ₂ 2 4.50* 4.50* 4.50* 0.223 4.026 8.360 9.332 15.387 10.52 22.16 Mo,isDo,7To,15 '22H ₂ O 3 GGMCC SO ₂ 3 4.50* 4.50* 4.50* 0.237 4,583 9.056 9.423 16.353 8.93 20.12 M0.22D0.4T0.38 24H ₂ O 4 GGMKK8O ₂ 4 4.50* 4.50* 4.50* 0.205 3.437 7.663 8.904 14.145 9.84 22.18 M0.3D0.2sT0.45 * 24H ₂ O 5 GGMCC SO2 5 4.50* 4.50* 4.50* 0.200 3.512 8.360 9.159 13,800 9.92 20.90 M0.1D0.75T0,is 22H ₂ O 6 GGMCC SO2 6 4.50* 4.50* 4.50* 0.196 3.862 7.663 9.088 13.524 7.84 17.67 M0.2D0.5T0p 31H ₂ O 7 GGMCC ON 7 4.50* 4.50* 4.50* 0.203 3.142 6.479 8.864 14.007 11.02 22.96 Mo.16Do.65To. ₂ '20H ₂ O 8 YYMCC ₂ 58 4.50* 4.50* 4.50* 0.195 3.273 7.106 8.843 13.455 10.81 22.75 Mo,25Do,4sTo,3 22H ₂ O 9 YGMCC II2^9 4.50* 4.50* 4.50* 0.207 3.437 7.454 8,884 14.283 10.83 23.61 MoP7Do,2sToP7 2IH2O ______10 GGMCC SO ₃ 10 4.50* 4.50* 4.50* 0.130 1.571 3.205 4.661 8,970 11.27 23.74 Mo,2sDo,sTo,25 20H ₂ O eleven YGMCC so ₃ 11 4.50* 4.50* 4.50* 0.140 1.555 3.225 4,640 9.660 11.03 23.24 M0.22D0.SsT0.23 20NgO 12 GGMCC SO312 4.50* 4.50* 4.50* 0.130 1.578 3.219 4,600 8,970 11.36 23.93 M0.i6D0.7T0.14 21H ₂ O 13 ymmkk at 13 4.50* 4.50* 4.50* 0.170 1.584 3.344 4,834 11,730 10.84 23.62 M0.13D0.75T0.12 21H ₂ O 14 ymmkk at 14 4.50* 4.50* 4.50* 0.180 1.604 3.358 4.813 12.420 11.07 23.32 Mo,1 7Do,64T0,19 ’ 19H3O 15 yymkk on is 4.50* 4.50' 4.50* 0.170 1.548 3.274 4,864 11,730 11.12 23.43 MopD0.4!'0.3 20H2O

*/ The calculated value of the indicator lies beyond the upper limit of the validated control method

The study of supramolecular properties was carried out, guided by the following principles:

1. Selection of conditions for changing the conformation of hydrogel molecules. In other words, selection of a 'key for locking/unlocking a 'guest' into a host [Supramolecular chemistry. Per. from English: in 2 volumes / John-

Claims (7)

tan W. Shame, Jerry L. Atwood. - M.: ICC Akademkniga, 2007]. 2. Checking the strength of the formed complex. In other words - resistance to breaking; 3. Recognition of a specific guest as a property of selectivity. To test the behavior of hydrogels of the host-guest type, UVVID absorption spectra were preliminarily recorded for equivalent solutions of the indicated substances (MO, CN, BR, BSA) at a pH of the medium in the range from 1.0 to 9.0 and vice versa - from 9.0 to 1.0 for adsorbate solutions other than BSA and at medium pH in the range from 3.0 to 8.0 and vice versa - from 9.0 to 1.0 for BSA solutions. The temperature range of the solutions varied from 40 to 60°C for BSA solutions and in the range from 40 to 80°C for solutions of other adsorbates. The study of the properties of hydrogels of the host-guest type was carried out by initially adding hydrochloric acid to the system containing the hydrogel and the adsorbate solution in an amount sufficient to achieve a pH value of 1.0 for the solution. Further study of the properties was carried out by changing the pH of the medium by adding sodium hydroxide solutions; when diluting the adsorbate solution by decantation with purified water; when heated and held at elevated temperatures. To be able to compare the adsorption activities of samples of different hydrogels, the previously measured adsorption activity in units of mg/g is normalized in the scale range from 0 to 1 (0-100%). The change in the relative adsorption activity of hydrogels depending on the pH of the medium is shown in Fig. 2. As can be seen from FIG. 2, samples of hydrogels obtained by the claimed method have a supramolecular, partially renewable host-guest property. In this case, the closure of the guest occurs at sufficiently low pH values of the medium and continues for pH values up to 8.5 units. Also unexpected was the ability of the samples to re-exhibit similar effects. Given that the pH value is close enough to the pH of the environment of the human stomach and intestines, manifestations of open properties will be useful from a medical point of view. Conducting studies with the dilution of the initial solutions of adsorbates by decanting with purified water and changing the temperature was carried out to exclude possible manifestations in the samples of the properties of only the adsorption component. Samples of hydrogels obtained by the method of the claimed revealed the typical behavior of supramolecular structures of the host-guest type as a reorganized conformationally mobile host. Decantation with purified water was carried out with the measurement of the optical density of the solution and recalculation of the concentration of the adsorbate. The hydrogels obtained by the method of the claimed method, as the decantations were carried out with purified water, partially desorbed the adsorbate in the range of 20-30% (MO, CN, BR) and 35-50% (BSA) and, as the pH of the solution changed, they behaved like the graph in Fig. 2. Heating solutions and exposure at temperatures in the range from 40 to 60 (80)°C do not cause obvious changes in performance. CLAIM 1. A method for producing a methylsilicic acid hydrogel with properties of supramolecular structures, according to which a sodium methylsiliconate solution is used, characterized in that a gaseous acidic agent is passed through the sodium methylsiliconate solution loaded into the reactor to perform bubbling, the resulting product is floated in the reactor neck, after the end of the process the product is unloaded from the reactor, evacuated to remove residual gas and washed with water purified to pH 6.5-7.0 and without residual anions, obtaining a methylsilicic acid hydrogel with the properties of supramolecular structures, which is described by the formula [{CH3Si(OH)2Oo.5}a/n{CH3Si(OH)O}b/n{CH3SiO1.5}c/n] xH2O, where I < x < 35; O < - < 0.38; 0.19 < - < 0.9; 0.11 < - < 0.4-9. p p p 2. The method according to claim 1, characterized in that the sparging time is 45 minutes, the sparging rate is 333 ml of a gaseous agent per minute. 3. The method according to claim 1, characterized in that carbon dioxide is used as a gaseous acidic agent, which is fed through the bottom valve of the reactor, carrying out the process in a closed system. 4. The method according to claim 1, characterized in that carbon dioxide is used as a gaseous acidic agent, which is fed through the top valve of the reactor, carrying out the process in an open system. 5. The method according to claim 1, characterized in that sulfur oxide (IV) - SO2 is used as a gaseous acidic agent. 6. The method according to claim 1, characterized in that hydrogen sulfide H2S is used as a gaseous acidic agent. 7. The method according to claim 1, characterized in that sulfur oxide is used as a gaseous acidic agent -