Water-soluble organosilicon derivatives of polyols and hydrogels based on said derivatives

FIELD: chemistry.

SUBSTANCE: water-soluble organosilicon derivatives of polyols are proposed, composition of which has formula (CH3)4-nSi(O-R-OH)n·x HO-R-OH in excess polyol, where R=-CH2-CH(OH)-CH2-, -CH2CH(CH3)-, (-CH2-CH2-O-)mCH2-CH2-, 0.5≤x≤2.9, n=2-4, m=7.7 or 12.0, with dynamic viscosity of 0.8-29.0 Pa·s (20±0.5°C), obtained by reacting (methyl)ethoxysilanes with polyols in molar ratio 1:(2.2-6.9) while heating the reaction mass to 120-130°C, maintaining this temperature for not less than 4 hours while stirring intensely with subsequent removal of the formed alcohol. Synthesis can take place in the presence of a catalyst, for example tetrabutoxy titanium - in amount of 0.04-0.06 mol per mole of (methyl)ethoxysilane. Also proposed a hydrogels based on said organosilicon derivatives of polyols, containing water and a gel-forming additive, with the following ratio of components in wt %: organosilicon derivatives of polyols in excess polyol 44.95 - 98.01; gel-forming additive 0.01-0.50; water - the rest. Proposed water-soluble organosilicon derivatives of polyols and hydrogels based on the said derivatives are physiologically active compounds, exhibit transcutaneous and vulnerary activity, have considerable effect on morphofunctional state of the skin and can be recommended as independent agents and as ointment bases of various pharmaceutical compositions with vulnerary activity.

EFFECT: obtaining novel water-soluble biologically active organosilicon derivatives of polyols which can be used as independent agents with transcutaneous and vulnerary activity and as bases of pharmaceutical compositions for local application.

3 cl, 2 dwg, 2 tbl, 16 ex

 

The invention relates to pharmaceutical industry and medicine, namely to new biologically active chemical compounds - water soluble organosilicon derivatives of polyols (glycerol, 1,2-propane diol, polyethylene glycol), and hydrogels based on them, which can be used as an independent means possessing transcutaneous, anti-inflammatory, wound healing, and regenerative activity, and the basics of pharmaceutical compositions for local application.

Known transdermal therapeutic system containing highly dispersed silicon dioxide, contributing to the penetration of active drug or other biologically active substances through the skin (Application U.S. No. 2004/0086552, AK 9/70, 2004). The penetration promoter, highly dispersed silicon dioxide, is used preferably in the form of Aerosil®200 and/or Aerosil®972, transdermal therapeutic system in the form of a plaster containing impermeable to the active ingredient sticky polymer film and a removable protective polymeric film. The patch can be made in the form of matrix systems or membrane systems with the tank. The content of highly disperse silicon dioxide in the adhesive layer of the patch may be 0.1-10 wt.%, preferably 2-5%. Additionally, using ethanol (p is imushestvenno) or oleic acid (5-10%); can also be used and other known accelerators penetration: 1,2-propandiol, polyethylene glycol, unsaturated and saturated fatty acids, their esters and salts, sulfoxidov and other connections.

Biologically active agents may be a variety of drugs used to treat cardiovascular disease, hormone replacement therapy, for the treatment of epilepsy, Parkinson's disease, pain, memory disorders, nicotine addiction and other diseases. Suitable biologically active agents can be, for example, anticholinergics and antihistamines, antipsychotics, antidepressants, analgesics, sympathomimetic agents, anticoagulants, cardiovascular medications and other medicines.

However, using a known means of highly disperse silicon dioxide (Aerosil) can lead to adverse effects associated with dehydration (drying) of the skin. In addition, mounted on the example on mouse skin (in vitro) the ability of Aerosil to accelerate percutaneous penetration of drugs is complemented by the use of known promoters of penetration, such as ethanol, which can also have negative side effects on the skin that substantially limits a wide range of specification is eskay activity known means.

Known water-soluble biologically active organosilicon compound of the formula [Si(CH3)2-O-CH2-CH(OH)-CH2-O-]nwhere n>1 (French Patent No. 2160293, AK 27/00, 07F 7/00, 1973). Well-known compound obtained by heating glycerol with dimethyldiethoxysilane or hexamethyldisilazane followed by distillation. Formed originally cyclic productspontaneously polymerizes when storing, into the above polymer is poly(dimethyl-1,1'-force-1-dioxa-2,6-hexanol-4). This compound is non-toxic and has a number of interesting therapeutic properties: it stimulates the formation of connective tissue, exhibits anti-inflammatory, regenerating and protective activity, is able to penetrate through the skin and promotes transdermal conductivity of medicines.

It can be used independently, for example in the form of a solution injection (0.25, 0.5 or 1.0%) or compresses, as well as in combination with medicinal additives in the local application, such as salicylic acid, which is especially effective in the case of electrophoresis.

The indications for the use of known means, including, in combination with a pharmaceutically acceptable conductors are any inflammatory processes, violation of arteria InEU and venous circulation, osteoporosis, burns. It is also possible cosmetic applications.

However, the disadvantages of the known means can be noted that the polymerization transformations during storage, as well as hydrolytic cleavage and subsequent condensation with the formation of active siloxane polymers (Mgorshkov, Vspilchevi, Wageline. Siloxane bond. Novosibirsk: Nauka, 1976, 413 S.), which reduces therapeutic efficacy of the tool. Used for local application, for example, compresses, low concentration means (not more than 1%) not effective enough without electrophoresis.

Known also glycerate silicon with transcutaneous conductivity of drugs, and glycerokinase on the basis of the composition Si(C3H7O3)4·x3H8About3·H2O, where 3≤x≤10, 20≤y≤40 (Patent RF №2255939, 07F 7/04, AK 47/30, 2005). Glycerate silicon obtained by the interaction of tetraethoxysilane with an excess of glycerol in the presence of a catalyst - tetraethoxysilane; glycerokinase are formed by the interaction of glycerate silicon with aqueous solutions of electrolytes.

Known compounds are non-toxic, have a high penetrating activity, have local antimicrobial effect of various degrees of severity and can be used to the in the form of separate funds for local use, and as a physiologically active basis transdermal therapeutic systems with possible wide range of applications in medicine.

However, the low content of silicon in the composition of funds, particularly hydrogels, is not sufficient for the manifestation of expressed self-healing effect. At the same time, it can be assumed that the introduction of a metal of groups in the molecular structure of glycerate silicon will have a positive effect on transcutaneous compounds and enhance their healing and regenerative action, as it will lead to an increase in the concentration of silicon and, in addition, to slow down the processes of hydrolysis and binding of silicon dispersed in an inactive phase (during the formation of hydrogels). Introduction of methyl groups, in addition, increases the lipophilicity of the molecule, which should facilitate the transmembrane migration of silicon through the lipid bilayer of cell membranes, i.e. the increase in transcutaneous activity.

The closest solution to the declared (prototype) is a biologically active silicon compound of General formula

in which a, b, C, D represent radicals different from-and HE associated with Si atoms by covalent bonds; two or three of these relations are relations of the type Si-O-C, Si-S-C or Si-N-C, hydro is Shemini in vivo with the formation of biologically active Si-OH linkages, especially when in contact with living tissues, a and D with the Si atoms of the formula (b) are always hydrolyzable. In fact, at least one of the compounds formed by hydrolysis, is a compound named stabilizing and preventing the formation of polymers of hydrolyzable linkages (U.S. Patent No. 6211393, 07F 7/18, AK 31/695, 2001).

As mentioned stabilizers, resulting from hydrolysis of the precursors of the formula (a) or (b)can be α - and β-hydroxycarbonate acid, glucuronide, gidroksilirovanii or phenolic amino acids such as serine, threonine or tyrosine; compounds containing several alcohol or phenol groups and, above all, close to alcohol (or phenol) functional groups; as stabilizers can be used, for example, glycol, catechin and catecholamine, polyethylene glycol, polyhydric alcohol such as glycerol, sugars and other compounds.

Known compounds, as well as therapeutic, dietetic and cosmetic compositions based on them are used in the form of capsules for oral administration, oily gels, eye creams, oily cream for massage (and other cosmetics). They have anti-inflammatory, regenerative, antidegradation, normalizing, antiradical and antigo yuusha activity and generally stimulate the body's defenses humans and animals.

However, a disadvantage of the known means is non-resistant to hydrolytic cleavage, which can lead to silanol condensation with the formation of active siloxane polymers, which ultimately reduces therapeutic efficacy funds; in addition, it is possible polymerization conversion of known means, what is happening in the case, if the substituents at the silicon atom contains foliolate group; it can also lead to reduction of therapeutic efficacy.

Also known is a method of obtaining biologically active compounds of silicon, which consists in the hydrolysis of the precursor having the above formula (a) or (b); however, the hydrolysis is carried out in a solvent containing a small amount of water, preferably between 0.1 and 5%, and consisting of alcohols, such as ethanol, isopropanol or fatty alcohol, such as cyclohexanol or octyldodecanol, glycols, such as propylene glycol, butyleneglycol, hexyleneglycol or polyethylene glycol; or miscible with water, organic solvents such as ethyl acetate or acetone (U.S. Patent No. 6172250, 07F 7/08, AC 7/06, 2001).

Biological activity of compounds of silicon, obtained in a known manner, is provided by their bioavailability and is observed only when they form in accordance with the ATA hydrolysis of siloxane oligomers or low molecular weight with a high content of highly polar functional Si-OH groups, able to education with stabilizers dynamic structures with a "hybrid" nature of the relationship (hydrogen, covalent).

Therapeutic compositions obtained using the known method of biologically active compounds of silicon are used in the form of an aqueous gel (for example, on the basis of carbopol), in the form of eye drops, dental applications (solution or gel for gums, chewing gum, and other means); cosmetic composition is in the form of a lotion, hair cream for face and other means.

As a disadvantage of this method may be noted the propensity for polymerization transformations are used as precursor compounds of the formula (a) or (b) in the case of polyfunctional hydroxyl-containing stabilizers such as glycerol, which can lead to reduction of therapeutic efficacy of the tool. In addition, the creation of pharmaceutical and cosmetic compositions using precursors of the formula (a) or (b) involves the use of organic solvents and a number of auxiliary substances: geleobrazovanie, stabilizers, emulsifiers, and other compounds, which significantly complicates the process of obtaining.

Thus, the authors of the present invention was to obtain new water-soluble Biol who cally active organosilicon derivatives of polyols, and hydrogels based on them having transcutaneous and wound healing activity, therapeutic efficacy of which remains at a high level due to their stability to hydrolytic cleavage and polymerization transformations.

This connection must be non-toxic, stable in storage, easy to obtain and well reproducible in the way of getting when using the available raw materials, suitable for practical use in the form of independent funds and local pharmaceutical compositions.

The problem is solved by the application of the new compounds, namely water-soluble organosilicon derivatives of polyols with transcutaneous and wound healing activity, which is in excess of polyol corresponds to the formula

(CH3)4-nSi(O-R-OH)n·x HO-R-OH,

where R=CH2-CH(OH)-CH2-, -CH2-CH(CH3)-, (-CH2-CH2-Oh)mCH2-CH2-,

0,5≤x≤2,9,

n=2-4,

m=7,7 or 12,0,

with a dynamic viscosity of 0.8-29.0 PA·s (20±0.5°C), obtained by the interaction of the (methyl)ethoxysilane with the polyol in a molar ratio of 1:(2,2-6,9) by heating the reaction mass to 120-130°C, holding at that temperature for at least 4 hours under vigorous stirring with the subsequent removal of the resulting alcohol.

At the same time, rastvorimye organosilicon derivatives of polyols can be obtained in the presence of a catalyst, for example tetraethoxysilane, in the amount of 0.04 to 0.06 mol per 1 mol (methyl)ethoxysilane.

The task is also solved by the use of hydrogels on the basis of organosilicon derivatives of polyols containing water and a gelling additive that as organosilicon derivatives of polyols contain at least one silicone derivative, the composition of which is in excess of polyol corresponds to the formula

(CH3)4-nSi(O-R-OH)n·x HO-R-OH,

where R=CH2-CH(OH)-CH2-, -CH2-CH(CH3)-, (-CH2-CH2-Oh)mCH2-CH2-,

0,5≤x≤2,9,

n=2-4,

m=7,7 or 12,0,

in the following ratio, wt.%:

organosilicon derivatives

polyols in excess polyol44,95-98,01
gelling additive0,01-0,50
waterrest

Currently in the patent and scientific literature is not known biologically active water-soluble organosilicon derivatives of polyols, which in excess polyol meets the above formula, and hydrogels based on them having transcutaneous and renosa is engaged in the activity, which would have been obtained by the proposed method and contained the components mentioned in the present interval.

Silicon is an essential element for the normal functioning of the human body. It is present in virtually all organs and tissues, especially rich in silicon connective tissue. Silicon is a structural component of mucopolysaccharides and protein complexes that form the frame of the connective tissue and determine its mechanical strength, elasticity and firmness. Silicon provides growth and hardening of connective tissue both during embryonic development and wound healing; promotes the biosynthesis of collagen and bone formation; plays an essential role in metabolic processes; prevents the deposition of cholesterol on the walls of blood vessels (M.G. Voronkov, Geelan, Alalawi. Silicon and life. Biochemistry, pharmacology and toxicology of compounds of silicon. Riga: zinatne, 1978, 586 C.). The silicon content in the organs and tissues in various diseases can vary considerably, and it is possible that the violation of its currency may cause a number of diseases.

Thus, the creation of medicines on the basis of silicon compounds is under a very specific biochemical basis and the two what is the actual problem.

The inventive water-soluble organosilicon derivatives of polyols (glycerol, 1,2-propane diol, polyethylene glycol), and hydrogels based on them have transcutaneous conductivity of medicines, wound healing, anti-inflammatory and regenerating activity, non-toxic and can be used in medicine and cosmetology.

Liquid water-soluble organosilicon derivatives of polyols can be used as a standalone tool, for example in the form of lotions, compresses, or in combination with active medicinal substances; in addition, they can be used as additives in various compositions, including, for composite hydrogels.

Hydrogels are a convenient form for local use. You can also use them independently and to create a soft medicinal forms. The structure of the gel provides a prolonged effect of the active drug additives, and transcutaneous activity - their deep penetration into the tissues of the body.

The method of obtaining the claimed novel compounds - water soluble organosilicon derivatives of polyols (glycerol, 1,2-propane diol, polyethylene glycol), which is in excess of polyol corresponds to the formula

(CH3)4-nSi(O-R-OH)n·x HO-R-OH,

where R=CH2-CH(OH)-CHsub> 2-, -CH2-CH(CH3)-, (-CH2-CH2-Oh)mCH2-CH2-,

0,5≤x≤2,9,

n=2-4,

m=7,7 or 12,0,

ease, efficiency, based on the use of inexpensive domestic raw materials and can be made by reaction of alcoholysis in excess polyol as follows:

The method involves the reaction of (methyl)ethoxysilane formula (CH3)4-nSi(OS2H5)nwhere n=2-4, with a polyol of the formula HO-R-OH where R=-CH2-CH(OH)-CH2-, -CH2-CH(CH3)-, (-CH2-CH2O)mCH2-CH2-, m=7,7 or 12,0, in a molar ratio of 1:(2,2-6,9) by heating the reaction mass to 120-130°C, holding at that temperature for at least 4 hours under vigorous stirring with the subsequent removal of the resulting ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. in the case of dimethyldiethoxysilane produced ethanol is removed as azeotrope, containing 81% of alcohol that involves the use of several more original dimethyldiethoxysilane: so, when x=0.5, the excess polyol (z) is 22.

The resulting products are clear, colorless (except for derivatives, poly (ethylene glycol) liquid with different viscosity, soluble in water and characterized by elemental analysis data, refractometry, X and viscometry. The dynamic viscosity was determined on the type of rotational viscometer Viscotester 6R. Measurement error of ±6%.

In the case of using the catalyst, tetraethoxysilane - Ti(OBu)4the response time is reduced by 3-4 times. The obtained products, due to the presence of a catalyst, are liquid white, infinitely miscible with water; also characterized by elemental analysis data, refractometry, X and viscometry.

Hydrogels based on at least one of the claimed compounds, the composition of which corresponds to the formula

(CH3)4-nSi(O-R-OH)n·x HO-R-OH,

where R=CH2-CH(OH)-CH2-, -CH2-CH(CH3)-, (-CH2-CH2-Oh)mCH2-CH2-,

0,5≤x≤2,9,

n=2-4,

m=7,7 or 12,0,

can be obtained as follows. To the obtained organosilicon derivatives of polyols in excess polyol at a temperature of 85-90°C and stirring an aqueous solution containing a gelling additive - Sol-electrolyte, such as NaCl, NaF, in the amount of from 0.01 to 0.50% of the total mass. Paramesh the existence and the heating is conducted until a homogeneous gel consistencies depending on the composition (content of organosilicon derivatives of polyols in excess of polyol is 44,95-98,01% of the total mass gel), transparent or translucent, white to colorless, odorless, stable in storage. The products were characterized by elemental analysis data, refractometry, X.

The chemistry of formation of organosilicon derivatives of polyols includes accelerated by a catalyst, such as tetramethoxysilane, the equilibrium reaction of alcoholysis (alkyl)alkoxysilanes polyols with removing the formed volatile alcohol to education products, the composition of which in excess of polyol corresponds to the formula

(CH3)4-nSi(O-R-OH)n·x HO-R-OH,

where R=CH2-CH(OH)-CH2-, -CH2-CH(CH3)-, (-CH2-CH2-Oh)mCH2-CH2-,

0,5≤x≤2,9,

n=2-4,

m=7,7 or 12,0.

An excess of polyol in the reaction contributes to its flow, prevents the formation of cyclic and polymeric products, gives consistency to the product suitable for practical use.

Upon receipt of the hydrogels excess polyol slows down the process of hydrolysis of organosilicon derivatives of polyols (due to their complexation with polyols) and subsequent condensation of the resulting silanols inactive siloxane polymers.

In the case of hydrogels excess polyol also plays a role softener (plasticizer), giving the gel soft and pliable and a good smazyvaesh the capability.

In the case of Tetra - and trifunctional organosilicon derivatives of polyols in the interaction with aqueous solutions is accelerated by various additives, for example salts, electrolytes, hydrolysis relations Si-O-C with the formation of silanol groups Si-OH and their subsequent condensation in disiloxane Si-O-Si groups, the role of cross-linking in the dispersed phase.

The resulting particles of the dispersed phase are connected in a loose spatial grid, which contains in its cells a dispersive medium, the system loses its fluidity, and a gel is formed. The dispersion medium is an aqueous solution of polyols containing active organosilicon derivatives of polyols, including partially hydrolyzed and oligomeric containing Si-OH groups, which, in the opinion of the authors, and provides healing and transcutaneous activity of the proposed drug (in the case of the hydrogel).

Stabilization of the formed gel helps complexing relations Si-O-Si, Si-O-C, C-O-H, N-O-N with the formation of solvatochromism.

In the case of joint use difunctional and Tetra - or trifunctional organosilicon derivatives of polyols formed composite hydrogels.

Research conducted by the authors, has allowed to determine the optimal composition of Appl is imago tools on the content of the polyol HO-R-OH in the formula (CH 3)4-nSi(O-R-OH)n·x HO-R-OH, where 0.5≤x≤2,9, and water content of the hydrogels, which is determined by the resistance and the most acceptable consistency of the proposed drug for practical use in the form of independent means, and the foundations of local pharmaceutical compositions.

The content of the electrolyte is less than 0.01 wt.% has a weak gelling action, and more than 0,50% does not contribute to gelation, but may lead to deterioration of the physico-chemical properties and/or adverse effects on the skin and the organism as a whole.

The following examples describe a method of obtaining organosilicon derivatives of polyols (examples 1-9) and hydrogels based on them (examples 10-16), and the determination of their acute toxicity, the study of wound healing and transcutaneous activity (for example, experimental animals).

Example 1. Synthesis of tetrakis(2,3-dioxirane)silane 2.9-molar excess of glycerol without catalyst (1.1) and in the presence of a catalyst (1.2)

Synthesis of organosilicon derivatives of polyols in examples 1-9 spend odnogolosy round bottom flask with a volume of 150 ml, equipped with tehnogas nozzle, a mechanical stirrer, a reverse refrigerator water and addition funnel.

1.1. To 48,29 g (0,524 mol) of glycerin with stirring, added dropwise 15,83 g (0,076 mol) of Tetra is doxycyline. The reaction mass is stirred for 12 hours at a temperature of 120°C, and then removed of ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 49,49 g (99%). The product is a colorless transparent viscous liquid with a dynamic viscosity of 28.8 PA·s (20±0.5°C), nD201,4790, soluble in water, alcohol, insoluble in chloroform and ether. The composition of the product corresponds to the formula Si(C3H7O3)4·2,93H8About3.

Found, %: C 37,28; N 8,15; Si Is 4.21. C20,7H51,2O20,7Si.

Calculated, %: C 37,70; N 7,83; Si 4.26 Deaths.

IR spectrum, νmaxcm-1: 3358 (HE); 2937, 2884 (C-H); 1111 (C-O C-O-N Deut.); 1047 (C-O C-O-N pri.); 1023 (Si-O-C).

1.2. To 48,13 g (0,523 mol) of glycerin with stirring, added dropwise 15,18 g (0,073 mol) of tetraethoxysilane and 0.99 g (of 0.003 mol) of tetraethoxysilane (0.04 mol/1 mol of tetraethoxysilane). The reaction mass is stirred for 4 hours at a temperature of 120°C, and then removed of ethyl and butyl alcohols, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (th which corresponds to a decrease of theoretical amount of alcohol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 49,52 g (99%). The product is a translucent, colorless, viscous fluid with a dynamic viscosity 29.0 PA·s (20±0.5°C), nD201,4793, infinitely miscible with water and alcohol, insoluble in chloroform and ether. The composition of the product corresponds to the formula Si(C3H7O3)4·2,93H8About3.

Found, %: C 37,22; N 8,13; Si 4,19. C20,7H51,2O20,7Si.

Calculated, %: C 37,70; N 7,83; Si 4.26 Deaths.

IR spectrum, νmaxcm-1: 3359 (HE); 2938, 2883 (C-H); 1110 (C-O C-O-N Deut.); 1047 (C-O C-O-N pri.); 1025 (Si-O-C).

Example 2. Synthesis of tetrakis(2-oxopropoxy)silane 2.9-molar excess of 1,2-propane diol without catalyst

To 43,42 g (0,573 mol) of 1,2-propane diol with stirring, added dropwise to 17.23 g (0,083 mol) of tetraethoxysilane. The reaction mass is stirred for 12 hours at a temperature of 120°C, and then removed of ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 44,95 g (99%). The product is a clear colorless liquid with a dynamic viscosity of 3.5 PA·s (20±0.5°C), nD201,4423, soluble in water, JV is the mouth, chloroform, insoluble in ether. The composition of the product corresponds to the formula Si(C3H7O3)4·2,93H8About3.

Found, %: C 44,52; N 9,70; Si 5,08. C20,7H51,2O13,8Si.

Calculated, %: C 45,28; N 9,40; Si 5,12.

IR spectrum, νmaxcm-1: 3368 (OH); 2971, 2932, 2879 (C-H); 1139, 1083 (S-O s-O-N Deut.); 1046, 991 (S-O s-O-N pri.); 1025 (Si-O-C).

Example 3. Synthesis of tetrakis(ω-exopolitics)silane 0.5-molar excess of polyethylene glycol (PEG-600) without catalyst

To 98,11 g (0,166 mol) PEG-600 with stirring, added dropwise of 7.69 g (0,037 mol) of tetraethoxysilane. The reaction mass is stirred for 15 hours at a temperature of 130°C, and then removed of ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 98,01 g (99%). The product is a clear colorless liquid with a dynamic viscosity of 6.0 PA·s (20±0.5°C), nD201,4688, soluble in water, alcohol, chloroform, insoluble in ether. The composition of the product corresponds to the formula Si(O[CH2CH2O]13H)4·0,NO[CH2CH2O]13N.

Found, %: C 51,98; N 9,12; Si 0,97. With117H239O 63Si.

Calculated, %: 52,39; N 8,98; Si 1,05.

IR spectrum, νmaxcm-1: 3337 (HE); 2870 (C-H); 1107 (C-O-C); 1023 (Si-O-C).

Example 4. Synthesis methyltris(2,3-dioxirane)silane 0.5-molar excess of glycerol without catalyst

To 78,00 g (0,847 mol) of glycerin with stirring, added dropwise 43,15 g (0,242 mol) methyltriethoxysilane. The reaction mass is stirred for 15 hours at a temperature of 130°C, and then removed of ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 86,92 g (99%). The product is a colorless transparent viscous liquid with a dynamic viscosity 25,0 PA·s (20±0.5°C), nD201,4773, soluble in water, alcohol, insoluble in chloroform and ether. The composition of the product corresponds to the formula.

Found, %: C 37,90; N 8,05; Si Of 7.85. With11,5H28O10,5Si.

Calculated, %: C 38,11; N 7,79; Si 8,11.

IR spectrum, νmaxcm-1: 3368 (OH); 2937, 2884 (C-H); 1270 (Si-C); 1111 (C-O C-O-N Deut.); 1047 (C-O C-O-N pri.); 1024 (Si-O-C).

Example 5. Synthesis methyltris(2 oxopropoxy)silane 0.5-molar excess of 1,2-propane diol without catalyst

To 74,57 g (0,980 mol) of 1,2-propane diol with stirring dropwise to ablaut 49,93 g (0,280 mol) methyltriethoxysilane. The reaction mass is stirred for 15 hours at a temperature of 130°C, and then removed of ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 84,89 g (99%). The product is a clear colorless liquid with a dynamic viscosity of 5.3 PA·s (20±0.5°C), nD201,4500, soluble in water, alcohol, chloroform, insoluble in ether. The composition of the product corresponds to the formula CH3Si(C3H7O2)3·0,5S3H8O2.

Found, %: C 45,13; N At 9.53; Si 9,02. With11,5H28About7Si.

Calculated, %: 45,08; N. Of 9.21; Si 9,17.

IR spectrum, νmaxcm-1is : 3370 (OH); 2972, 2932, 2877 (C-H); 1267 (Si-C); 1084 (C-O C-O-N Deut.); 1043, 990 (C-O C-O-N pri.); 1023 (Si-O-C).

Example 6. Synthesis methyltris(ω-exopolitics)silane 0.5-molar excess of polyethylene glycol (PEG-400) without catalyst

To 93,80 g (0,235 mol) PEG-400 with stirring dropwise dobavlyaut 11,95 g (0,067 mol) methyltriethoxysilane. The reaction mass is stirred for 15 hours at a temperature of 130°C, and then removed of ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary COI is to the constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 96,37 g (99%). The product is a transparent liquid light yellow color with a dynamic viscosity of 3.9 PA·s (20±0.5°C), nD201,4643, soluble in water, alcohol, chloroform, insoluble in ether. The composition of the product corresponds to the formula CH3Si(O[CH2CH2O]8,7N)3·0,NO[CH2CH2O]8,7N.

Found, %: C 50,99; N 9,25; Si 2,14. With61,9H128,8O34Si.

Calculated, %: 51,47; N 8,99; Si 1,94.

IR spectrum, νmaxcm-1: 3350 (OH); 2873 (C-H); 1272 (Si-C); 1111 (C-O-C); 1023 (Si-O-C).

Example 7. Synthesis of dimethyldi(2,3-dioxirane)silane in a 1-molar excess of glycerol without catalyst (7.1) and in the presence of a catalyst (7.2)

7.1. To 83,16 g (of 0.903 mol) of glycerin with stirring, added dropwise 50,56 g (0,341 mol) of dimethyldiethoxysilane. The reaction mass is stirred for 15 hours at a temperature of 130°C, then removed the azeotrope of ethanol and dimethyldiethoxysilane first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 100,00 g (100%). The product is a colorless transparent viscous liquid with a dynamic viscosity of 18.0 PA·s 20±0.5°C), soluble in water, alcohol, insoluble in chloroform and ether, nD201,4705. The composition of the product corresponds to the formula (CH3)2Si(C3H7O3)2·3H8O3.

Found, %: C 39,33; N Charged 8.52; Si To 8.34. C11H28O9Si

Calculated, %: C 39,75; N 8,49; Si 8,45.

IR spectrum, νmaxcm-1: 3368 (O-H); 2934, 2880, 1409 (C-H); 1260 (Si-C); 1111 (C-O C-O-N Deut.); 1047 (C-O C-O-N pri.); 1025 (Si-O-C).

7.2. To 74,47 g (0,809 mol) of glycerin with stirring, added dropwise 41,52 g (0,280 mol) of dimethyldiethoxysilane and 5,72 g (of 0.017 mol) of tetraethoxysilane (0.06 mol/1 mol of dimethyldiethoxysilane). The reaction mass is stirred for 5 hours at a temperature of 130°C, and then removed of ethyl alcohol (in the form of an azeotrope with dimethyldiethoxysilane) and butyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical amount of alcohol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 100,00 g (100%). The product is a viscous liquid white, infinitely miscible with water and alcohol, insoluble in chloroform and ether with a dynamic viscosity of 18.2 PA·s (20±0.5°C), nD201,4716. The composition of the product corresponds to the formula (CH3)2Si(C 3H7O3)2·3H8About3.

Found, %: C 39,68; N 8,99; Si Scored 8.38. C11H28O9Si.

Calculated, %: C 39,75; N 8,49; Si 8,45.

IR spectrum, νmaxcm-1: 3368 (OH); 2934, 2880, 1409 (C-H); 1260 (Si-C); 1111 (C-O C-O-N Deut.); 1040, 994 (S-O s-O-N pri.); 1026 (Si-O-C).

Example 8. Synthesis of dimethyldi(2 oxopropoxy)silane in a 1-molar excess of 1,2-propane diol without catalyst

To 80,26 g (1,055 mol) of 1,2-propane diol with stirring, added dropwise 59,22 g (0,399 mol) of dimethyldiethoxysilane. The reaction mass is stirred for 15 hours at a temperature of 130°C, and then removed of ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 100,00 g (100%). The product is a clear colorless liquid, soluble in water, alcohol, chloroform, insoluble in ether with a dynamic viscosity of 0.8 PA·s (20±0.5°C), nD201,4334. The composition of the product corresponds to the formula (CH3)2Si(C3H7O2)2·3H8About2.

Found, %: C 46,28; N 9,96; Si 9,75. C11H28O6Si.

Calculated, %: C 46,45; N 9,92; Si 9,88.

IR spectrum, νmaxcm-1: 3368 (O-H); 2931, 2876,1458, 1408 (C-H); 1259 (Si-C); 1141 (C-O C-O-N Deut.); 1043 (C-O C-O-N pri.); 1047 (Si-O-C).

Example 9. Synthesis of dimethyldi(ω-exopolitics)silane 0.5-molar excess of polyethylene glycol (PEG-400) without catalyst

To 94,68 g (0,237 mol) PEG-400 with stirring, added dropwise 16,01 g (to 0.108 mol) of dimethyldiethoxysilane. The reaction mass is stirred for 15 hours at a temperature of 130°C, and then removed of ethyl alcohol, first at atmospheric pressure, then under vacuum on a rotary evaporator to constant weight of the reaction mass (which corresponds to a decrease of theoretical quantity of ethanol) at a residual pressure of 2-5 mm Hg and a temperature of 130°C. the product Yield 100,00 g (100%). The product is a transparent liquid pale yellow, soluble in water, alcohol, chloroform, insoluble in ether with a dynamic viscosity of 2.8 PA·s (20±0.5°C), nD201,4605. The composition of the product corresponds to the formula (CH3)2Si(O[CH2CH2O]8,7H)2·0,5 BUT[CH2CH2O]8,7N.

Found, %: C 51,99; N 9,19; Si 2,62. C45,5H96O24,3Si.

Calculated, %: C Won With 51.75; H 9,16; Si 2,66.

IR spectrum, νmaxcm-1: 3336 (O-H); 2870, 1455 (C-H); 1255 (Si-C); 1107 (C-O); 1047 (C-O C-O-N pri.); 952 (Si-O-C).

Example 10. Synthesis of hydrogel based on tetrakis(2,3-dioxirane)silane

To 49,49 g (0,075 mol) of the product obtained according the example 1.1, with stirring, poured in portions 50,51 g of sodium chloride solution, containing 0.46 g (0,008 mol) sodium chloride (0.46% of the total mass). Gelation is carried out at heating (85-90°C) and stirring. The yield of 100.00 g (100%). The product is a translucent, colorless gel, nD201,4015. The gel is not soluble in the usual organic solvents, are not completely soluble in water. The composition of the product corresponds to the formula Si(C3H7O3)4·2,93H8About3·N2O.

Found, %: C 18,71; N 13,79; Si 2,03. C20,7H125,2O57,7Si.

Calculated, %: C 18,75; N 13,41; Si 2,11.

IR spectrum, νmaxcm-1: 3390 (OH); 2944, 2888 (C-H); 1111 (C-O C-O-N Deut.); 1641 (H-O-H); 1046, 992 (C-O C-O-N pri.); 1024 (Si-O-C).

Example 11. Synthesis of hydrogel based on tetrakis(2-oxopropoxy)silane

To 44,95 g (0,082 mol) of the product obtained according to example 2, with stirring, poured in portions 55,05 g of sodium chloride solution containing 0.50 g (0,009 mol) sodium chloride (0,50% of the total mass). Gelation is carried out at heating (85-90°C) and stirring. The yield of 100.00 g (100%). The product is a translucent, colorless gel, nD201,3917. The gel is not soluble in the usual organic solvents, are not completely soluble in water. The composition of the product corresponds to the formula Si(C3H7O2)4·2,C 3H8O2·N2O.

Found, %: C 20,05; N 10,49; Si To 2.29. C20,7H125,2O50,8Si.

Calculated, %: C 20,45; N 10,38; Si 2,31.

IR spectrum, νmaxcm-1: 3340 (OH); 2976, 2936, 2884 (C-H); 1136, 1079 (S-O s-O-N Deut.); 1643 (H-O-H); 1044, 990 (S-O s-O-N pri.); 1025 (Si-O-C).

Example 12. Synthesis of hydrogel based on tetrakis(ω-exopolitics)silane

To 98,01 g (0,0365 mol) of the product obtained according to example 3, with stirring, poured in portions of 1.99 g of a solution of sodium fluoride containing 0.01 g (is 0.0002 mol) of sodium fluoride (0.01% of total mass). Gelation is carried out at heating (85-90°C) and stirring. The yield of 100.00 g (100%). The product is a clear, colorless gel, nD201,4673. The gel is not soluble in the usual organic solvents, are not completely soluble in water. The composition of the product corresponds to the formula Si(O[CH2CH2O]13H)4·0,NO[CH2CH2O]13N·3H2O.

Found, %: C 51,04; N 9,15; Si 0,94. With117H245O66Si.

Calculated, %: 51,36; N 9,03; Si Of 1.03.

IR spectrum, νmaxcm-1: 3340 (OH); 2871 (C-H); 1643 (H-O-H); 1111 (C-O-C); 1024 (Si-O-C).

Example 13. Synthesis of hydrogel-based methyltris(2,3-dioxirane)silane

To 86,92 g (0,240 mol) of the product obtained according to example 4, with stirring, poured in portions 13,08 g of sodium chloride solution containing 0.12 g (0.002 mol) of sodium chloride (0.12%of the total mass). Gelation is carried out at heating (85-90°C) and stirring. The yield of 100.00 g (100%). The product is a translucent, colorless gel, nD201,4554. The gel is not soluble in the usual organic solvents, are not completely soluble in water. The composition of the product corresponds to the formula CH3Si(C3H7O3)3·0.5 s3H8About3·3H2O.

Found, %: C 33,04; N 8,55; Si 6.42 Per. C11,5H34Oof 13.5Si.

Calculated, %: C 33,17; N 8,23; Si 6,74.

IR spectrum, νmaxcm-1: 3368 (OH); 2937, 2883 (C-H); 1273 (Si-C); 1643 (H-O-H); 1109 (C-O C-O-N Deut.); 1040, 994 (S-O s-O-N pri.); 1024 (Si-O-C).

Example 14. Synthesis of hydrogel-based methyltris(2 oxopropoxy)silane

To 84,89 g (0,277 mol) of the product obtained according to example 5, with stirring, poured in portions 15,11 g of sodium chloride solution containing 0.14 g (0.002 mol) of sodium chloride (0.14% of the total mass). Gelation is carried out at heating (85-90°C) and stirring. The yield of 100.00 g (100%). The product is a translucent, colorless gel, nD201,4287. The gel is not soluble in the usual organic solvents, are not completely soluble in water. The composition of the product corresponds to the formula CH3Si(C3H7O2)3·0,5C3H8O2·3H2O.

Found, %: 38,46; N 9,67; Si 7,56. C11,5H34O10Si.

Vicis is prohibited, %: 38,32; N 9,51; Si 7,79.

IR spectrum, νmaxcm-1: 3368 (OH); 2971, 2932, 2878 (C-H); 1643 (H-O-H); 1273 (Si-C); 1084 (C-O C-O-N Deut.); 1043, 991 (S-O s-O-N pri.); 1023 (Si-O-C).

Example 15. Synthesis of hydrogel-based methyltris(ω-exopolitics)-silane

To 96,37 g (0,067 mol) of the product obtained according to example 6, with stirring, poured in portions 3,63 g of a solution of sodium fluoride containing 0.02 g (of 0.0005 mol) of sodium fluoride (0.02% of the total mass). Gelation is carried out at heating (85-90°C) and stirring. The yield of 100.00 g (100%). The product is a translucent gel light yellow color, nD201,4628. The gel is not soluble in the usual organic solvents, are not completely soluble in water. The composition of the product corresponds to the formula CH3Si(O[CH2CH2O]8,7N)3·0,NO[CH2CH2O]8,7N·3H2O.

Found, %: C 49,49; N To 9.32; Si 1,57. C61,9H134,8O37Si.

Calculated, %: C 49,61; N 9,07; Si 1,87.

IR spectrum, νmaxcm-1: 3350 (OH); 2872 (C-H); 1644 (H-O-H); 1273 (Si-C); 1111 (C-O-C); 1024 (Si-O-C).

Example 16. Synthesis of composite hydrogel based on tetrakis(2,3-dioxirane)silane, dimethyldi(2,3-dioxirane)silane

To a mixture consisting of 44,405 g (0,067 mol) of the product obtained in example 1, and 11,19 g (0,0335 mol) of the product obtained according to example 7, with stirring, poured in portions 44,405 g of the solution of the chloride is sodium, containing 0.40 g (to 0.007 mol) of sodium chloride (0.4% of the total mass). Gelation is carried out at heating (85-90°C) and stirring. The yield of 100.00 g (100%). The product is a translucent, colorless gel, nD201,4094. The gel is not soluble in the usual organic solvents, are not completely soluble in water. The composition of the product corresponds to the formula Si(C3H7O3)4·0,5(CH3)2Si(C3H7O3)2·3,4 C3H8O3·N2O.

Found, %: C 21,13; N Being 9.61; Si 2,59. C26,2H139,2O62,2Si.

Calculated, %: C 21,09; N 9,40; Si 2,82.

IR spectrum, νmaxcm-1: 3400 (OH); 2943, 2887 (C-H); 1641 (H-O-H); 1264 (Si-C); 1110 (C-O C-O-N Deut.); 1045, 993 (S-O s-O-N pri.); 1027 (Si-O-C).

Determination of acute toxicity

Tests conducted in the Ural state medical Academy.

The study of the acute toxicity of the claimed means of organosilicon derivatives of polyols (examples 1-9) and hydrogels based on them (examples 10-16), conducted according to the Guidance on experimental (preclinical) study of new pharmacological substances (M.: ZAO "JJA (Presidium)", 2000, 398 S.) on white rats subtype of Vistar line of both sexes weighing 180-230 g Experimental animals were kept in a vivarium at a temperature of 18-20°C under natural light cycle on standard dietary free access to food and water.

The analyte was injected into the stomach through a tube and intraperitoneally once in the form of liquid substances (for organosilicon derivatives of polyols) or in the form of a 50-percentage aqueous suspensions (in the case of hydrogels).

After the introduction of the investigated substances hourly observed the behavior of the animals during the first day, and in the next 13 days daily. During the experiment were recorded depending on the dose of General locomotor activity of animals, neuromuscular excitability, reflexes (pain, corneal), autonomic response (salivation, diuresis, defecation).

It is established that the investigated products do not exhibit toxic properties: define LD50failed in the case of hydrogels obtained in examples 10-16 - all experimental animals remained alive. Significantly significant deviations in the behavior of animals were found.

For organosilicon derivatives of polyols values LD50(intragastrically) was more than 6000 mg/kg

Thus, the subjects matter, organosilicon derivatives of polyols in excess of polyol and hydrogels based on them (according to GOST 12.1.007-76), are low-toxic compounds (IV class of danger).

The study of transcutaneous activity

The essence of the method consists in measuring the degree of diffusion of the investigational product, including,in the presence of transcutaneous conductors, through natural biological membranes of intact skin (in vitro).

As a medicinal drug diffusing through the skin, used diclofenac sodium, with an initial concentration of drug in isotonic solution was 1%.

As the study transcutaneous conductors were selected organosilicon derivatives (including gel) different functionality (n=2-4), obtained using various polyols (glycerol, 1,2-propane diol, polyethylene glycol-400) (table 1).

Table 1
The study of the permeability of diclofenac sodium on the skin of rats subtype of Vistar line in the presence of various additives transcutaneous wires
№ p/p (group)# exampleStudied transcutaneous wires (10%)The extent of percutaneous permeability*after 20 hours at 37±2°C
%The relative value
11.1Si(C3H7O2)4·2,9C3H8O21,20±0,05 1,5
210Si(C3H7O3)4·2,9C3H8About3·N2About0,99±0,041,2
34CH3Si(C3H7O3)3·0,5S3H8About31,62±0,062,0
45CH3Si(C3H7O2)3·0,5S3H8About21,04±0,041,3
56CH3Si(O[CH2CH2O]8,7N)3·0,NO[CH2CH2O]8,7N0,77±0,030,9
67.1(CH3)2Si(C3H7O3)2·3H8About31,71±0,072,1
7-DMSO0,82±0,031,0
Note: *p<0,05 in all cases when compared with DMSO.

Investigated as transcutaneous electrical connections used at a concentration of 10% in isotonic. The comparison was carried out with known transcutaneous guide, dimethylsulfoxide (DMSO), in the same concentration.

Experiments were performed using as biological membranes isolated skin of male rats subtype of Vistar line taken from the anterior abdominal wall under the General ether anesthesia. The flaps of skin were released from subcutaneous fat, washed with saline, and then examined with a magnifying glass on the integrity of the superficial part of the epidermis. Prepared in this way the skin is firmly fixed as a membrane in a specially specifically designed diffusion chambers, consisting of two cell volume of ~7 ml. In one of the cells was filled with the test solution, in other isotonic.

All experiments in each series (7 experiments in 7 diffusion chambers) was performed in parallel at the same temperature (37±2°C) and exposure time (20 hours). The series was repeated until satisfactory convergence results (3-5 episodes).

The concentration passed through the skin of diclofenac sodium was determined by means of UV-spectroscopy on the spectrophotometer, Shimadzu UV-2401 PC. Calibration was performed according to the absorption band at 275 nm. From calibro the full-time schedule was determined by the molar concentration of diclofenac sodium, passing through the entire thickness of the skin, then calculate its mass, knowing the volumes of the solutions in the appropriate cells. The extent of percutaneous permeability was evaluated in % of the original weight of diclofenac sodium.

As follows from the table, all study tools demonstrate the properties of the transcutaneous conductors and superior to the activity of the drug comparison - DMSO. The most active substance is difunctional organosilicon derivative of glycerol (group 6). Somewhat less active than DMSO, organosilicon derivative of polyethylene glycol (group 5).

Study of wound healing actions

The research was conducted on the example of the healing process simulated burn white rats subtype of Vistar line weighing 180-230 g Rats were divided into 6 groups of 10 animals each. All rats were inflicted burns II-III degree on the skin of the lateral area of 20×60 mm, which corresponded to 4% of the total area of the skin of the animal. In rats experimental groups area of the burn was treated with the inventive means, rat 6 (control) group treatment is not received (table 2).

As the study tools were also selected organosilicon derivatives of various functions (n=2-4), obtained using various polyols (glycerol, 1,2-propane diol, polyethylene glycol-400), and hydrogels to them about the Nove (including, combined). Lubrication was performed daily for 18-22 days 0.5 g until full wound healing in all groups.

Table 2 shows the timing of wound healing in stages: 1 - the formation of granulation tissue, 2 - exclusion of granulations; 3 - active epithelization with the formation of a scar.

Table 2
Terms of wound healing thermal burns experimental and control groups of rats subtype of Vistar line when using the claimed funds
№ p/p (group)no prima-RAComposition of productThe healing time, stage (day)Effectiveness of
of treatment*, %
123
12Si(C3H7O2)4·2,9C3H8O26,7±0,711,0±1,214,0±0,833,3
27(CH3)2Si(C3H7O3)2 ·3H8O36,7±0,913,0±1,815,2±0,827,6
311.1Si(C3H7O2)4·2,9C3H8O2·N2O7,0±0,714,0±1,416,0±0,923,8
412CH3Si(O[CH2CH2O]8,7N)3·0,5 BUT[CH2CH2O]8,7N·3H2O7,0±0,814,0±1,416,0±0,923,8
516Si(C3H7O3)4·0,5(CH3)2Si(C3H7O3)2·3,4 C3H8O3·37 H2O6,7±0,811,0±1,314,0±0,833,3
6-Without treatment (control group)8,9±1,017,0±1,8 21,8±0,9-
Note:*p<0,05 in all cases when comparing the experimental data with the control.

As can be seen from the table, complete wound healing in the control group was observed ~ 21 days. The most noticeable shortening of the healing took place in groups 1 and 2 (organosilicon derivatives of propane diol and glycerol, respectively), and group 5 (combined hydrogel); however, significant changes in terms of wound healing in these groups was not observed. In General, all of the investigated tools are pronounced healing activity compared to control in terms of healing: the effectiveness of treatment is a 23.8 33.3 per cent.

Before applying the burns and on the 14th day of treatment investigated the behavioral responses of animals (open field). After treatment the animals was General and biochemical blood tests, and morphological studies of visceral organs and structures of the skin.

Histological specimens were prepared after fixation of tissues (heart, lungs, liver, kidneys, adrenal glands, spleen, skin) 10%formalin solution and were filled with wax. Histological sections were stained with hematoxylin and eosin by van gieson. The analyzed organs without manifestations of structural changes.

the study open field was assessed by vertical and horizontal activity of animals on the following parameters: time of leaving the circle, the number of covered squares, the number of stevani, washings and zaglyadyvanie in burrows. The greatest decline in all indicators were observed in the control group. Some decrease in activity was observed in rats of the 3rd and 4th groups - in the case of hydrogels.

In General and biochemical blood tests significant changes after treatment were not identified; the performance of animals in the study groups did not differ from that of intact animals.

When assessing the morphological structure of the skin revealed some morphological and functional manifestations. From the analysis of the histogram plot of the burn control rats, it follows that in the area of the burn is determined by the necrosis of the epidermis with perifocal granulocyte reaction; the capillaries and venules papillary and Podmoskovie layers expanded with the phenomena of capillaroscopy; in the perifocal area in the papillary layer - cell proliferation fibroblastoma number; in the thickness of the dermis and hypodermis are defined perivascular lymphoid infiltrates localized alopecia.

The most favorable results were observed in rats 1, 2 and 5-th groups, and in these cases more pronounced formation of perifocal lymph leukocyte shaft, and decreased destruction and necrosis of the epidermis.

It should be noted that in all cases the treatment was absent the inflammation and purulent exudate, there was observed the formation of significantly more elastic after-burn scars and visible appearance woolly cover.

Figure 1 and 2 shows pictures of burn surface, respectively, for rats of the control and the experimental group (5th) after treatment is 21 days. See education woolly cover the surface of keloids experienced rats and less pronounced post-burn scar.

Thus, studies have shown that water-soluble organosilicon derivatives of polyols and hydrogels based on them are physiologically active compounds show transcutaneous and wound-healing effect, have a significant impact on morphological and functional condition of the skin and can be recommended as an independent means, and as ointment bases of various pharmaceutical compositions wound healing, anti-inflammatory, regenerating and transcutaneous actions.

1. Water-soluble organosilicon derivatives of polyols with transcutaneous and wound healing activity, which is in excess of polyol corresponds to the formula
(CH3)4-nSi(O-R-OH)n·x HO-R-OH,
where R=-CH2-CH(OH)-CH2-, -CH2-CH(CH3)-, (-CH2-CH2-Oh)mCH2-CH2-,
0,5≤x≤2,9,
n=2-4,
m=7,7 or 12,0,
with a dynamic viscosity of 0.8-29.0 PA·s (20±0.5°C), the obtained interaction (methyl)ethoxysilane with the polyol in a molar ratio of 1:(2,2-6,9) by heating the reaction mass to 120-130°C, holding at that temperature for at least 4 h with vigorous stirring with the subsequent removal of the resulting alcohol.

2. Water-soluble organosilicon derivatives of polyols with transcutaneous and wound healing activity obtained according to claim 1, characterized in that the synthesis products is carried out in the presence of a catalyst, for example, tetramethoxysilane in the amount of 0.04 to 0.06 mol per 1 mol (methyl)ethoxysilane.

3. Hydrogels based on organosilicon derivatives of polyols containing water and a gelling additive that as organosilicon derivatives of polyols contain at least one silicone derivative, the composition of which is in excess of polyol corresponds to the formula
(CH3)4-nSi(O-R-OH)n·x HO-R-OH,
where R=-CH2-CH(OH)-CH2-, -CH2-CH(CH3)-, (-CH2-CH2-Oh)mCH2-CH2-,
0,5≤x≤2,9,
n=2-4,
m=7,7 or 12,0,
in the following ratio, wt.%:

organosilicon derivatives
polyols in excess polyol44,95-98,01
gelling additive0,01-0,50
waterrest



 

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18 cl, 180 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the method of obtaining the compound of the formula (IV) , which includes the epoxidation of the compound of the formula (I) the agent of oxidation in the presence of optically active compound with the formation of the compound of formula (II) , adding the gent to break the reaction, in order to extinguish any surplus oxidising agent present, where the agents for breaking the reaction are tri(C1-C6)alkylphosphite; without the isolation of the compound of the formula (II), the interaction of the reaction mixture, which includes the compound of the formula (III) in the presence of the base and the cleaning of the compound of the formula (IV) by crystallisation. The invention also relates to the method of obtaining the compound of the formula (IX) , which includes the reaction of the compound of formula (IV) with a silylation agent with the formation of a compound of the formula (V) ; the reaction of the compound of formula (V) with the silylation agent of the formula R'SO2X, where R' represents the remainder of sulfonic acid (C1-C6) alkyl and the X represents the detached group, with the obtaining of the compound of formula (VII) ; the substitution of the sulphonyloxy-group with the obtaining of the compound of the formula (VIII) and reaction of the compound of the formula (VIII) with ammonia or a compound of ammonia obtaining a compound of the formula (IX). The invention also relates to the intermediate compounds (V) and (VI) The compound of the formula (IX) can be used for obtaining a biologically active material - (S, S) - reboxetin. . In the given structural formulas pit independently are equal to 0 or a whole number from 1 up to 5; each of the groups R and R1, which can be identical or different, represents C1-C6 alkoxy or C1-C6 alkyl; P represents the protective group; R' represents the remainder of sulfonic acid (C1-C6) alkyl.

EFFECT: obtaining aril ethers.

14 cl, 5 ex

FIELD: organic chemistry, chemical technology, vitamins.

SUBSTANCE: invention relates to novel intermediate compounds used for synthesis of derivatives of vitamin D and represented by the formula (I): wherein Y1 represents hydrogen atom or tert.-butyldimethylsilyl group; Y2 represents tert.-butyldimethylsilyl group; Y3 represents hydrogen atom or tetrahydro-2-pyranyl group wherein Y3O-group is in R-configuration; R1 and R2 are bound and form methylene group. Except for, invention relates to novel compounds represented by the formula (II): wherein Y2 represents tert.-butyldimethylsilyl group; Y3 represents hydrogen atom or tetrahydro-2-pyranyl group and Y3O-group is in R-configuration. These compounds are used as intermediate substances for synthesis of compounds of the formula (I).

EFFECT: valuable properties of intermediate compounds.

8 cl, 1 dwg, 8 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes mercaptosilanes of the general formula (I): wherein R1 represents residue of simple alkyl polyester of the formula: -O-(R5-O)m-R6. These compounds are synthesized by the catalytic interaction of a corresponding silane with an alkoxylated alcohol R1-H by splitting off group R7-OH. And this group R7-OH is removed from the reaction mixture in continuous or periodic regimen. Indicated mercaptosilanes are used as components of rubber mixtures. Rubber mixture is prepared by mixing rubber or rubber mixture, filling agent and, if necessary, additional components and at least one indicated mercaptosilane in a corresponding mixer for rubber. Claimed mercaptosilanes are used in making molded articles, pneumatic tires, race protectors, cable envelopes, hoses, driving belts, conveyer bands, covers for different rollers, tires, shoes soles, thickening rings and shock absorbers. Taking into account economy, short duration of process in mixing components and under providing conditions for possibility the following processing the claimed mercaptosilanes allow attaining high strengthening degree, minimizing hysteresis losses and enhancing stability against abrasion in simultaneous decreasing releasing alcohols to environment as compared with trimethoxy- and triethoxy-substituted mercaptosilanes.

EFFECT: improved method of synthesis, valuable properties of rubber mixtures.

16 cl, 16 tbl, 23 ex

FIELD: medicine.

SUBSTANCE: present invention concerns therapeutic compositions for treating skin diseases, such as wounds, abrasions, ulcers, burns, infections, irritations, microbial, mud and water exposures, psoriasis, acne, scars, age spots, sclerosis and other physical or chemical damages, which contain cationic organosilane quaternary ammonium compounds and hydrogen peroxide in the aqueous medium.

EFFECT: invention also concerns the methods of therapeutic purification and skin treatment with said compositions.

35 cl, 5 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention concerns cosmetology and dermatology, namely to creation of an agent for foot care at chronic venous insufficiency (CVI) of the lower limbs. The agent for foot care at chronic venous insufficiency of the lower limbs, characterised by that it represents a gel and contains a complex perfume thickener, a micellar solution of dihydroquercetin, liposomal concentrate, microemulsion concentrate including silicon-fluoroorganic liquids, a bile solution. Gel is intended for reduction of weariness of feet, normalisation and restoration of a microcirculatory bed of a skin and subcutaneous fat, reduction of puffiness and morbidity for long time.

EFFECT: maintenance of neogenesis of cells of a skin and an endothelium of vessels.

3 cl, 3 ex, 15 tbl, 5 dwg

FIELD: medicine.

SUBSTANCE: 24 hours prior to the examination, children aged 3 to 8 year old takes in 100 ml lactulose (Duphalac) with water of room temperature in amount 1-1.5 liters within 4-6 hours. The second dose lactulose (Duphalac) 100 ml follows with water of room temperature in amount 1-1.5 liters. To prevent overaerogenesis and to reduce discomfort, Espumisan (Simethicone) is prescribed in dosage 15 ml 3 times a day. For children aged 8 to 18 years old, there is prescribed 200 ml lactulose (Duphalac) with water of room temperature in amount 1.5-2.0 litres within 4-6 hours followed with the second dose of lactulose (Duphalac) 200 ml with water of room temperature in amount 1-1.5 litres. Additionally Espumisan (Simethicone) is introduced in dosage 15 ml 3 times a day or 3-6 capsules 3 times a day.

EFFECT: effective cleansing of gastrointestinal tract in children of different age, thus ensuring good visualisation of large intestine mucosa and decreasing drug load on organism of younger children, preserving normal microflora of large intestine and preventing overaerogenesis.

2 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, particularly obstetrics and hestosis treatment for the pregnant. Method involves endovascular laser irradiation of blood for six days. Further, polyphepan is administered internally for eight days in the dosage of 0.5 g per kg of pregnant body weight for 3-4 times per day.

EFFECT: therapeutic effect with reduced treatment duration and medication load on organism of the pregnant due to the selected regimen.

1 ex

FIELD: medicine.

SUBSTANCE: antibacterial and rehydration therapies are combined with prescribed sorbents, symptomatic therapy. From first day of disease prescribed is infusion herb collection consisting of silverweed rhizome, salvia leaves, milfoil herb, St. John's wort herb, inula rhizomes with roots, tickseed herbs, mint leaves, fennel fruits and buckthorn bark at ratio of components 2:2:2:2:2:2:2:2:1. Infusion is taken up dosed 1\3 glass 3 times a day, 30 min before meal within 10 days. Then within three weeks after basic therapy appoint infusion from silverweed rhizome, salvia leaves, milfoil herb.

EFFECT: provides accelerated normalisation of clinical-laboratory indicators, and prevention of infectious complications without by-effects.

2 cl, 1 tbl, 1 ex

FIELD: medicine; pharmacology.

SUBSTANCE: agent contains organic-silica sorbate as methyl silica acid hydrogel, non-organic sorbates aerosol or clay minerals. The agent contains one or several species of alive or killed eubacteria as a microbal mass, from the following groups: Bifidobacteria, lactobacilli and streptococci, which amount is calculated from mass of sorbate aqueous suspension, in addition, the agent contains the plant extraction. An acceptable ointment base can be added to the agent. The agent can be made as an ointment, the emulsion ointment (cream), or as a paste. The method includes preparation of 5-95% aqueous suspension, which consists of sorbate composition, and following insertion of alive or killed microbial mass to specified limits, then the plant extractions is added and the mixture is stirred until complete homogenisation.

EFFECT: agent shows the significant antiviral and antimicrobial effects.

5 cl, 4 tbl, 4 ex, 6 dwg

FIELD: medicine.

SUBSTANCE: method involves treating injured skin regions with low intensity electromagnetic radiation in bandwidth of 30-300 GHz acting with modulated signal of 0.03 Hz of 0.1 MkW/cm2. Organosilicon glycerohydrogel Si(C3H7O3)4xC3H8O3yH2O , where 3≤x≤10, 20≤y≤40, is applied to ulcer boundary at the end of every irradiation session at a dose of 0.1 g per 1 cm2 of injured surface.

EFFECT: deep drug penetration into tissues; stimulated reparative processes.

FIELD: medicine, surgery.

SUBSTANCE: invention describes an agent used in topical treatment of suppurative sluggish vast surface wounds that comprises boric acid, pepsin and sorbent based on highly-dispersed silica in the following ratio of components, g: boric acid, 5; pepsin, 10, and sorbent based on highly-dispersed silica, 20. Using the proposed agent provides reducing cleansing and epithelization of wound and treatment period of a patient in hospital.

EFFECT: improved and valuable medicinal properties of agent.

2 ex

FIELD: chemistry of organosilicon compounds, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds and their using in therapy. Invention describes compounds of the formula (I): wherein radical are given in the invention claim. These substances are claimed as compounds possessing antagonistic activity with respect to GnRH, and pharmaceutical composition comprising these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

18 cl, 7 ex

FIELD: chemistry of organosilicon compounds, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds and their using in therapy. Invention describes compounds of the formula (I): wherein alternate values are given in the invention claim. These substances are claimed as compounds possessing antagonistic activity with respect to GnRH, and pharmaceutical composition comprising these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

28 cl, 3 ex

FIELD: veterinary science.

SUBSTANCE: on should apply 1-(ethoxy)sylatrane as a stimulating agent for reproductive capacity in female furred animals and viability of their offspring. The innovation enables to improve reproductive function in females and viability of whelps.

EFFECT: higher efficiency.

3 ex, 3 tbl

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