Hydrogel material based on cross-linked polyvinyl alcohol
SUBSTANCE: invention relates to medicine, namely to medicinal hydrogel polymer materials, used as a base for the creation of polymer implants and products, contacting with blood. Described is a non-porous hydrogel material based on a modified polyvinyl alcohol, which contains unsaturated radicals in side chains, obtained by polymerisation at 0-250°C in a solution or in polymer powder sintering at 100-180°C. Also described is a combined material, containing a matrix of the porous hydrogel polymer material and reinforcing filler, filling the matrix, of the non-porous hydrogel material obtained by the said method.
EFFECT: materials are liquid-impermeable, possess biocompatibility, high strength characteristics and high stability at heating.
3 cl, 3 ex
The technical field
The present invention relates to medicine, namely to medical hydrogel polymeric materials and products on their basis, including, for creating polymeric implants and articles in contact with blood.
Materials based on polyvinyl alcohol are widely used in medical fields. A typical example of that can be attributed to the analogues of the material, is the material described in the monograph SATHE R. D. Design And Development of a Novel Implantable Prosthetic Vein Valve // A Thesis Presented to The Academic Faculty, Georgia Institute of Technology, May, 2006.
In this case, a material traditionally obtained on the basis of physical hydrogels of high molecular weight polyvinyl alcohol formed in the cycles of thawing-freezing" [cryogels).
A significant disadvantage of this technical solution is the relatively low thermal stability of this material [HASSAN, S. M., STEWART J. E., PEPPAS N. A. Diffusional characteristics of freeze/thawed poly(vinyl alcohol) hydrogels: Applications to protein controlled release from multilaminate devices // European Journal of Pharmaceutics and Biopharmaceutics, 2000, V. 49, p.161 to 165), soluble at temperatures close to the boiling temperature of water. The consequence of this is the need for fixing structure using cross-linking agents and/or radiation hard. This greatly complicates the technology which increases the risk of complications in the practical application of the material, associated with the possibility of incomplete cleaning material from the cross-linking agents and products of radiation-induced destruction of polyvinyl alcohol.
The closest analogue of the present invention is a gel material on the basis of modified polyvinyl alcohol containing in the side chain double bond (patent RU 2328313, "Macroporous gel material and products on its basis", published 10.07.2008). Cross-linking of molecules in obtaining polymeric material is in this case not due to hydrogen bonds, and by chemical crosslinking by free radical mechanism. Therefore, this material does not require additional fixing structure and high stability when heated. However, the known polymeric material on the basis of modified polyvinyl alcohol is formed in the water-frozen solutions that require very specific hardware design, in addition, the resulting material has a porous structure and is permeable to liquids, which does not allow to use it as a structural material, for example, to create products for cardiovascular surgery.
Disclosure of inventions
Object of the present invention is to provide a hydrogel material suitable for use as design the frame in cardiovascular surgery, including, to create a polymeric implants and articles in contact with blood.
The technical result of the invention is to provide a non-porous hydrogel material based on polyvinyl alcohol, which is impervious to liquids, possessing biocompatibility, high mechanical strength and high stability when heated.
This technical result is achieved by obtaining non-porous hydrogel material based on the modified polyvinyl alcohol of General formula (I)
R represents H,
R3represents an unsaturated group selected from CH2=CH-CO-O-,
CH2=CH-O-CH2-CH2-O - or
R4-CH3or the residue of another acid, polyvinyl ether which was obtained polyvinyl alcohol,
n=75-99,5 molar percent (mol.%),
k=0.5 to 25 mol.%,
when carrying out the polymerization at a temperature 0-250°C in solution or when is pecunia powder polymer at a temperature of 100-180°C.
The use of the modified polyvinyl alcohol of General formula (I) containing in the side chain double bond, as the basis for obtaining hydrogel material allows to obtain a hydrogel material that does not require additional fixing structure, which eliminates the risk of toxicity due to the presence of cross-linking agents. This material also has a high stability when heated.
Conducting polymerization under conditions of high temperatures, i.e., without the step of freezing the polymer solution, was suddenly possible to obtain on the basis of modified polyvinyl alcohol of General formula (I) hydrogel material having the desired characteristics: non-porous, biocompatible, high strength, impermeable to liquids and heat stable, i.e., a material suitable for use as structural in cardiovascular surgery, including, for creating polymeric implants and articles in contact with blood.
As the basis for the hydrogel material used modified polyvinyl alcohol of General formula (I), which is a water-soluble derivatives of polyvinyl alcohol with a molecular weight Mw=5000-1000000.
Introduced into a side chain unsaturated radicals R3contains one or two unsaturated communication and which allows the formation of spatial patterns in radical polymerization and copolymerization. The radical R3may contain the residue of an unsaturated acid, for example, acrylic, methacrylic, sorbic, crotonic, cinnamic:
or alanovoy group, for example,
The number of groups with multiple bonds contained in the side chain of the polymer, can vary (k=0.5 to 25 mol.%), however, it should be sufficient to achieve the desired degree of crosslinking of polyvinyl alcohol in accordance with the desired physical and functional properties of a material, such as, for example, the hardness of the resulting gel (from soft to hard). Therefore, the number of such groups may be different depending on the destination of the material. So, for example, to increase the strength of the material, the number of such groups in the polymer composition can be large, while for increasing the ductility of the material can be used a polymer with a lower degree of substitution.
Synthesis of hydrogels can be carried out in a solution of modified polyvinyl alcohol, during sintering of the powder of the polymer. The solvent can act as water and organic solvents (for example, formamide, dimethylformamide, a solution of dimethyl sulfoxide, dimethylacetamide, etc. and their mixtures. The concentration of the solution may be in the range from 0.5 to 30 wt.%. The process can be carried out in the presence of radical polymerization initiators (for example, organic and inorganic peroxides), and in their absence - by thermal initiation. Temperature of synthesis (0÷250°C) is determined experimentally and is caused by the type of solvent and/or initiator. The sintering powder of the polymer is conducted at a temperature of 100-180°C.
In addition, this method allows you to enter in the composition of the material at the stage of formation of additional functional groups, which allows to obtain composite materials based on polyvinyl alcohol. The receipt of such materials is possible by adding at the stage of joining to the modified polyvinyl alcohol of General formula (I) various low molecular weight unsaturated comonomers, such as acrylamide, isopropylacrylamide, etilenglikolevykh, acrylic methacrylic, sorbic, crotonic, cinnamic acid, dimethylaminoethylacrylate, diethylaminoacetate, etc. may be entered, p is at least one of the additional functional groups. The introduction of additional functional groups allows you to expand the range of characteristics of the final product, for example, makes it possible to adsorption on the material surface proteins or drugs due to electrostatic interactions between the carrier and the surface groups of the adsorbed substances in that case, if the composition of the material entered the charged group.
The proposed method can also be applied to obtain a composite material containing a matrix of a porous hydrogel polymer material obtained by conducting polymerization of the modified polyvinyl alcohol of General formula (I) in water frozen solutions, as described in more detail in the patent RU 2328313, and a reinforcing filler, representing non-porous hydrogel material based on the modified polyvinyl alcohol of General formula (I) obtained by conducting polymerization in solution. Receiving the combined material is carried out by modifying and filling the matrix of the porous hydrogel polymeric material is a non-porous hydrogel of polyvinyl alcohol. Thus, to obtain a combined material polymerization macromer [modified polyvinyl alcohol General the formula (I) in solution (water, based and organic solvent) is performed on lyophilized porous film, placed on a Teflon substrate.
The obtained composite material has better mechanical properties.
The implementation of the invention
1) Example of a film material.
A portion of the modified polymer based on polyvinyl alcohol composition
(m=94,4 mol.%; n=4,3 mol.%, k=l,3 mol.%, Mw=25 000) weighing 1 g was dissolved by heating in 25 ml of distilled water, cooled to room temperature, was added 0.06 g of potassium persulfate in 1.5 ml of distilled water, the mixture was evacuated to remove dissolved air. Then poured in a Teflon shape so that the thickness of the water layer does not exceed 1 mm Uniform was placed in a heat chamber and was heated at 80°C for 1 h, then was dried to constant weight at a temperature of 90°C. At the end of the process the resulting film was washed in 200 ml of hot distilled water, and then dried at a temperature of 80°C to constant weight.
The resulting material has porosity and looks like a translucent film that is stable at temperatures close to the boiling temperature of water, over an indefinite period of time.
2) an Example of obtaining a combined material containing a matrix of porous geroge is avago polymer material.
To obtain a combined material use a matrix of porous hydrogel (porosity 10-90%, the average pore size of 0.1-100 μm), obtained in the following way: a portion of the modified polymer based on polyvinyl alcohol composition, similar to that specified in example 1, weighing 1 g was dissolved by heating in 25 ml of distilled water, cooled to room temperature, was added 0.06 g of potassium persulfate in 1.5 ml of distilled water, the mixture was evacuated to remove dissolved air. The mixture is then cooled to a temperature of 5°C was added 30 μl of N,N,N',N'-tetramethylethylenediamine. The mixture was poured into pre-cooled glass shape so that the thickness of the water layer was not more than ~0.5 mm, were frozen and kept for 6 hours at a temperature of -15°C. after the reaction form was unfrozen, the resulting macroporous hydrogel was washed in 200 ml of hot distilled water, and then freeze-dried.
Then, for reinforcement of the material and give it better mechanical properties, the resulting matrix is additionally modify and fill isotropic porous gel of polyvinyl alcohol as follows:
lyophilized porous film was placed on a Teflon substrate and applied to it a solution of macromer containing persulfate received similar is the rule example 1, then placed in a heat chamber and heated at 80°C for 1 h, the resulting film was washed with 300 ml of hot distilled water and dried to constant weight at 90°C.
3) Example of a film material, optionally containing charged groups
A portion of the modified polymer based on polyvinyl alcohol composition
(m=94,4 mol.%; n=4,3 mol.%, k=l,3 mol.%, Mw=25 000) weighing 1 g was dissolved by heating in 25 ml of distilled water, cooled to room temperature, was added 0.2 g of acrylic acid, and then 0.15 ml of 3% hydrogen peroxide solution and 0.3 ml of 15% solution of ascorbic acid, the mixture was evacuated to remove dissolved air. Then poured in a Teflon shape so that the thickness of the water layer does not exceed 1 mm, and kept for 4 hours at room temperature. Then the form was placed in a heat chamber and dried to constant weight at a temperature of 90°C. At the end of the process the resulting film was washed in 200 ml of hot distilled water, and then dried at a temperature of 80°C to constant weight.
The resulting material has porosity and looks like a translucent film, heat stable, and in addition, contains up to 10 mol.% the charged parts of acrylic acid.
1. A method of obtaining a non-porous hydrogel material on the again of the modified polyvinyl alcohol of General formula (I)
R represents H,
R3represents an unsaturated group selected from
CH2=CH-O-CH2-CH2-O - or
R4-CH3or the residue of another acid, polyvinyl ether which was obtained polyvinyl alcohol,
k=0.5 to 25 mol.%,
by conducting the polymerization at a temperature 0-250°C in solution or during sintering powder of the polymer at a temperature of 100-180°C.
2. The method according to p. 1, characterized in that at the stage of carrying out polymerization to the modified polyvinyl alcohol of General formula (I) optionally introducing at least one low molecular weight unsaturated comonomer selected from acrylamide, isopropylacrylamide, etilenglikolevykh, acrylic, methacrylic, sorbic, crotonic, cinnamic acid, dimethylaminoethylacrylate and diethylaminoacetate.
3. Composite material for use as structural in cardiovascular surgery, containing the s matrix of a porous hydrogel polymer material, obtained by carrying out polymerization of the modified polyvinyl alcohol of General formula (I) in water frozen solutions, and a reinforcing filler that fills the matrix, and represents a non-porous hydrogel material obtained by conducting polymerization in the solution method under item 1.
SUBSTANCE: invention relates to production technology of films having increased fire-resistance, particularly to films based on polyvinyl alcohol and can be used in various industries and economics for fireproof modification of the materials based on them. According to the method methylphosphite borate is preliminary mixed with plasticiser at the ratio 1:4 and 1-5% of aqueous solution of polyvinyl alcohol is added. Thereafter, films are moulded and dried at the ambient temperature. Glycerin, glycol alcohol or diethylene glycol is used as a plasticiser.
EFFECT: invention allows simplifying modification, increasing reliability and fire resistance of films.
1 tbl, 3 ex
SUBSTANCE: invention concerns technology for obtaining polyvinyl alcohol films, particularly composition for film modification intended for enhanced fire and heat resistance, and can be applied in various fields of industry, science, technology and agriculture. Claimed composition includes 5-10% aqueous solution of methylphosphite borate and 5-10% aqueous solution of chitosan at the following component ratio, weight parts: methylphosphite borate - 5-10; chitosan - 5-10; water - 190-180.
EFFECT: improved fire and heat resistance of polyvinyl alcohol films.
2 tbl, 3 ex
SUBSTANCE: invention concerns improvement technology for films based on polyvinyl alcohol with enhanced fire and heat resistance, and can be applied in various fields of industry, science, technology and agriculture. Method involves polyvinyl alcohol films processing by mix of 5-10% aqueous solution of methylphosphate borate and 5-10% aqueous solution of chitosan at the weight ratio of 1:1, and drying.
EFFECT: obtainment of non-toxic biologically degradable and environmentally safe films with enhanced fire and heat resistance.
1 tbl, 3 ex
FIELD: polymer materials.
SUBSTANCE: invention provides a method for manufacturing polyvinyl alcohol-based modified films with elevated fire resistance by means treatment with phosphorus-containing compounds. In particular, 5-15% aqueous solution of methyl phosphite borate is used and films are treated during 1-2 min and then dried at ambient temperature. Thus obtained polymers are characterized by good film-forming properties, exhibit self-extinction capability, and show water absorption at a level of 1.14%. Films can be used in various industry and national economy fields.
EFFECT: improved performance characteristics of films.
1 tbl, 3 ex
FIELD: organic chemistry, polymers.
SUBSTANCE: invention relates to low-branched high-molecular polyvinyl acetate, methods for its preparing and to polyvinyl alcohol prepared on its base. Invention describes low-branched high-molecular polyvinyl acetate prepared by aqueous-emulsion polymerization of vinyl acetate in the presence of emulsifier and initiating agent wherein complexes of alkylcobalt (III) with tridentate ligands of the general formula (I) are used as an initiating agent taken in the amount 0.04-0.2 mas. p., and the polymerization process is carried out at temperature 10-40°C. Polyvinyl acetate prepared by this method has molecular mass 850000 Da, not less, and degree of branching 0.39-0.7. Polyvinyl alcohol with the polymerization degree 6000 Da, not less, and the saponification degree 98-99.9% that is able for making high-module fibers is prepared by saponification of indicated low-branched polyvinyl acetate.
EFFECT: improved preparing method, valuable properties of product.
3 cl, 3 tbl, 10 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine. Described are biomaterials prepared by mixing an autocross-linked derivative of hyaluronic acid with hyaluronic acid derivative cross-linked with 1,4-butandiol diglycidyl ether (BDDE) in a weight ratio from 10:90 to 90:10, as new fillers.
EFFECT: biomaterials make is possible to promote the immediate regeneration/restoration of dermal/skin tissue, which has lost its initial tightness.
7 cl, 2 dwg, 16 ex
SUBSTANCE: there are described compositions containing hyaluronic acid with a low degree of modification of functional groups, and mixtures prepared by a controlled reaction of this slightly modified hyaluronic acid with applicable difunctional or polyfunctional cross-linking agents. The compositions possess the low anti-inflammatory properties in injection in vivo and can be used as medical devices, biomedical adhesives and sealing matters.
EFFECT: targeted delivery of the bioactive substances.
49 cl, 14 dwg, 24 tbl, 45 ex
SUBSTANCE: bioactive porous 3D-matrix for tissue engineering involves a resorbed partially crystalline polymer having a porosity of 60-80% and a pore size of 2 to 100 mcm. A biopolymer gel having a particle size of 30-100 mcm is incorporated into a portion of the pores. A polymer/gel ratio makes 99:1 to 50:50 wt %. The matrix is prepared by grinding a mixture of gel and polymer powder having an average particle size of 100 mcm, and the prepared mixture fills prepared moulds to be placed in a high-pressure chamber wherein the temperature is increased to 25-40°C first, and then the CO2 pressure is increased to 4.0-25.0 MPa. The system is kept in the above environment for 1 hour, and then the chamber pressure is discharged to an atmospheric one for 30-120 minutes; thereafter the temperature is decreased to a room value, and the patterns are removed.
EFFECT: ensuring flexibility of using the matrix in various organs and systems, no toxicity, higher ability to tissue regeneration stimulation, prolonged effect of biostimulation.
6 cl, 5 ex, 1 tbl, 4 dwg
SUBSTANCE: conduit wall is presented by a material of random micro- and nanofibres of a bioresorptive polymer of poly(ε-caprolactone), and the content is presented by a self-assembled nanostructured hydrogel of acetyl-(Arg-Ala-Asp-Ala)4-CONH2(PuraMatrix™) oligopeptide. The above conduit is implanted in a complex with the direct local delivery of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) genes to be introduced into the proximal and distal nerve segments, while the formed conduit is implanted into a nerve rupture, and its ends are fixed with epineural sutures.
EFFECT: invention provides a stimulating effect on the invasion of regenerative medullated fibres, on the recovery of motor and sensitive nerve function, and enables improving the effect of the recovery of the nerve structure and function after the extended ruptures.
SUBSTANCE: claimed invention is aimed at manufacturing intraocular lens (IOL), for introduction of posterior eye chamber in form of PC Phakic lens. IOL is formed from hydrogel material, formed by cross-linked polymer and copolymer component. Lens includes UV chromophore, which is benzotriazole.
EFFECT: IOL hydrogel material usually has relatively high index of refraction and/or possesses desirable degree of protection against irradiation.
12 cl, 3 tbl
SUBSTANCE: invention relates to medicine. Described is implant, which can be injected in subcutaneous or intracutaneous way in form of monophase hydrogel, which contains gel, obtained from cross-linked hyaluronic acid and one of its physiologically acceptable salts.
EFFECT: obtaining subcutaneous implant used for filling wrinkles and stimulation of epidermal cells and/or supporting mechanical properties of skin density and elasticity.
15 cl, 2 ex
SUBSTANCE: invention relates to field of medicine, in particular to method of obtaining form-preserving aggregates of gel particles, in which aggregates are held together by physical forces of non-covalent bonds, such as hydrophobic-hydrophilic interactions and hydrogen bonds. Method of obtaining form-preserving aggregates of gel particles includes introduction of preliminarily obtained suspension of gel particles in polar liquid, where gel particles have absolute electrochemical potential, into receiving medium, in which absolute electrochemical potential of gel particles decreases, which results in fusion of gel particles into form-preserving aggregate.
EFFECT: invention allows to obtain form-preserving gel aggregates in situ so that form of aggregate is determined by place of application.
49 cl, 35 ex, 11 tbl, 33 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine, more specifically to biocompatible alginate systems with the delayed gelatinisation process. There are offered sets and compositions for making a self-gelatinised alginate gel containing sterile water-soluble alginate and particles of sterile water insoluble alginate with a gelling ion. There are offered methods for dosing self-gelatinised alginate dispersion for making the self-gelatinised alginate gel. The methods can include dosing the dispersion in an individual. There is offered the self-gelatinised alginate gel of the thickness more 5 mm and not containing one or more sulphates, citrates, phosphates, lactates, EDTA or lipids. There are offered implanted devices coated with the homogeneous alginate gel. There are offered methods for improving viability of pancreatic islets or other cell aggregate or tissue, after recovery and while stored and transported.
EFFECT: group of inventions provides creation of the alginate gelling system which contains alginate and the gelling ions with high biological compatibility; enables the gelatinisation process without pH variations, connected with the other systems, and requires minimum ingredients, thus provides variation of gelatinisation time and gel strength depending on the specific requirements.
62 cl, 11 dwg, 2 tbl, 27 ex
SUBSTANCE: invention relates to a method of producing biologically compatible gel which is thickened with cross-linked polymer by cross-linking a given amount of at least one biologically compatible natural polymer in a solution by adding a defined amount of cross-linking agent, an additional amount of polymer with molecular weight over 500000 dalton in a solution, in which the reaction mixture is diluted to reduce concentration of polymer in the solution, and the cross-linking reaction is stopped by removing the cross-linking agent.
EFFECT: gel and its use for separating, replacing or filling biological tissue or for increasing volume of such tissue, or supplementing or replacing biological fluid.
11 cl, 1 tbl, 4 ex
SUBSTANCE: invention concerns medicine. Particles of the viscoelastic material chosen from group, consisting of polysaccharides and their derivatives which are suitable for injection with gel particles having the size in a range from 1 to 5 mm at action of a physiological saline solution are described. An implant for increase of volume of the soft tissues, containing particles of the viscoelastic material chosen from group, consisting of polysaccharides and their derivatives where the basic volume of the specified particles represents the gel particles, suitable for injection and having the size in a range from 1 to 5 mm at action of a physiological saline solution, is described. The way of increase of volume of soft tissues at a mammal, including a human being, including subepidermal introduction in a place of a body of the specified mammal in which it is desirable to enlarge volume of soft tissues is described.
EFFECT: augmentation of volume of soft tissues at a mammal.
24 cl, 4 ex
FIELD: medicine-destination polymers.
SUBSTANCE: invention relates to biologically stable hydrogels to be employed as endoprosthesis consisting essentially of following components: polyacrylamide including acrylamide, crosslinked methylene-bis-acrylamide, wherein acrylamide and methylene-bis-acrylamide are linked at molar ratio from 150:1 to 1000:1. Hydrogel is rinsed with water or physiologic solution so that it contains about 0.5-3.5% polyacrylamide and less than 50 ppm acrylamide and methylene-bis-acrylamide monomers, while modulus of elasticity of hydrogel is approximately 10 to 700 Pa and its complex viscosity about 2 to 90 Pa*sec. Rinsing stage allows removal of nearly all amounts (even trace amounts) of above-indicated monomers resulting in lower toxicity and higher stability of hydrogel. Biologically stable hydrogel is used as injectable prosthesis to fill soft tissues and also to treat or prevent urinary incontinence or anal incontinence. Hydrogel, obtained in a few stages including combining acrylamide and methylene-bis-acrylamide, initiating radical polymerization, and rinsing with apyrogenic water or physiologic solution, is also useful in treatment or prevention of bladder-ureter reflux in mammalians. In all these cases biologically stable hydrogels contain between 0.5 and 25% polyacrylamide.
EFFECT: enlarged resource for manufacturing endoprostheses.
10 cl, 3 dwg, 7 tbl
SUBSTANCE: method of antibiotics fixation within porous implants is described. Result of method application lies in possibility of reliable fixation of antibiotic solution within porous implant and arrangement of favourable conditions for haemostasis in operative wound due to application of 10% gelatine solution as antibiotic carrier. Specified result is achieved by filling porous implants with antibiotic solution in liquid gel. For this purpose implant is dipped in solution by 3/4. Filling occurs under the influence of capillary forces. After solution cooled to form dense gel, antibiotic is fixed in implant pores and gradually released after installation to bone defect area.
EFFECT: reliable fixation of antibiotic solution within porous implant and arrangement of favourable conditions for haemostasis in operative wound.
3 cl, 1 ex
SUBSTANCE: invention concerns medicine, namely to reconstructive surgery, traumatology-orthopedy, maxillofacial surgery, stomatology and can be applied at osteo-plastic operations. For delivery of medical products immediately in a zone of defect and their prolonged influence in the centre of a lesion medicinal preparations are dissolved in a normal saline solution in a dose providing local effect, collagen-containing component is added to a solution in the ratio 9-20 g: 100 ml of a solution also admix with the carrier from dispersed allotransplants in the ratio of 1:1-3.
EFFECT: method allows lowering a dose necessary for reception of medical effect in 10 times, and also allows accelerating reparative processes in a defect zone.